Speech audiometry in noise: Development of the French-language VRB (vocale rapide dans le bruit) test

Publication date: Available online 30 July 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): F. Leclercq, C. Renard, C. Vincent

Abstract

Introduction

Understanding speech in noise is a major challenge for most hearing-impaired subjects, with or without hearing aids. To overcome the weaknesses of French-language speech-in-noise tests, we developed a new instrument, with a balanced mix of difficulty of the speech material.

Material and methods

The speech material comprised 127 sentences taken from the "Marginal Benefit from Acoustic Amplification" (MBAA) corpus, each including 3 keywords. The noise was created using the "onde vocale globale" (global vocal wave: OVG), described by Dodelé. The 127 speech/noise pairs were recorded individually after root-mean-square equalization. The first experiment, on 10 normal-hearing adults, determined the signal-to-noise ratio (SNR) associated with 50% correct keyword identification in each sentence (SNR-50), using an ascending method with noise level set at 73 dB SPL. Relative levels between sentences and noise were then adjusted sentence by sentence to achieve an SNR-50 of 0 dB. The second experiment, with 12 normal-hearing adults, validated the equalization of sentence difficulty.

Results

Mean SNR-50 was −6.64 dB (σ = 1.47). Mean adjusted SNR-50 was 0.08 dB (σ = 0.55). Mean psychometric curve slope was 19.3%/dB, with low standard deviations, testifying to the sensitivity of the speech material.

Conclusion

The VRB (vocale rapide dans le bruit: rapid speech in noise) test is based on sentences from the MBAA corpus with background noise based on the OVG at different signal-to-noise ratios. The test is feasible and able to detect slight variations in speech-in-noise performance between subjects.

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Zinc deficiency and severe protein–energy malnutrition in a child with atopic eczema

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2mZF5z6

The Prognostic Impact of Tumor Size in Papillary Thyroid Carcinoma is Modified by Age

Thyroid, Ahead of Print.


https://ift.tt/2Kd00I3

Early Determinants of Thyroid Function Outcomes in Children with Congenital Hypothyroidism and a Normally Located Thyroid Gland: A Regional Cohort Study

Thyroid, Ahead of Print.


https://ift.tt/2LKefZR

Protective Effect of Ginseng on Salivary Dysfunction Following Radioiodine Therapy in a Mouse Model

Thyroid, Ahead of Print.


https://ift.tt/2KcjsEM

A Novel Mutation in NKX2-1 Shows Dominant-Negative Effects Only in the Presence of PAX8

Thyroid, Ahead of Print.


https://ift.tt/2LKefsP

Iron Deficiency May Predict Greater Risk for Hypothyroxinemia: A Retrospective Cohort Study of Pregnant Women in China

Thyroid, Ahead of Print.


https://ift.tt/2M2rmSN

Predicting Malignancy in Thyroid Nodules: Radiomics Score Versus 2017 American College of Radiology Thyroid Imaging, Reporting and Data System

Thyroid, Ahead of Print.


https://ift.tt/2vnfzHN

In Memoriam to the man behind the camera: David J LIM, MD November 27 1935–June 29, 2018

Publication date: Available online 30 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Bernd Fritzsch

https://ift.tt/2KcrugW

In vivo imaging reveals increased eosinophil uptake in the lungs of obese asthmatics

Publication date: Available online 30 July 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Neda Farahi, Chrystalla Loutsios, Nicola Tregay, Adam K.A. Wright, Rachid Berair, Laurence S.C. Lok, Daniel Gillett, Ian Cullum, Rosalind P. Simmonds, Charlotte Summers, Anna Wong, Chandra K. Solanki, John Buscombe, Pee Hwee Pang, Arthikkaa Thavakumar, A.Michael Peters, Christopher E. Brightling, Alison M. Condliffe, Edwin R. Chilvers

Capsule Summary

Using radiolabeled eosinophils coupled with SPECT/CT the authors quantify eosinophilic inflammation in the lungs of patients with asthma and focal pulmonary eosinophilic inflammation, revealing important differences in eosinophil kinetics between obese and non-obese asthmatics.

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Sulfide protects Staphylococcus aureus from aminoglycoside antibiotics but cannot be regarded as a general defense mechanism against antibiotics [PublishAheadOfPrint]

Sulfide production has been proposed to be a universal defense mechanism against antibiotics in bacteria (Shatalin K, Shatalina E, Mironov A and Nudler E. Science 334:986-90,2011, doi: 10.1126/science.1209855). To gain insight into the mechanism underlying sulfide protection, we systematically and comparatively addressed the interference of sulfide with antibiotic activity against Staphylococcus aureus as model organism. The impact of sulfide and sulfide precursors on the antibiotic susceptibility of S. aureus towards the most important classes of antibiotics was analyzed using modified disk diffusion assays, killing kinetics and drug uptake studies. In addition, sulfide production and the impact of exogenously added sulfide on the physiology of S. aureus was analyzed. Sulfide protection was found to be limited to aminoglycoside antibiotics, known to be taken up by bacterial cells in an energy dependent process. The protective mechanism was found to rely on an inhibitory effect of sulfide on the bacterial respiratory chain leading to reduced drug uptake. S. aureus was found to be incapable of producing substantial amounts of sulfide. We propose that bacterial sulfide production should not be regarded as a general defense mechanism against antibiotics since, (i) it is limited to aminoglycosides and (ii) production levels vary considerably among species and, as for S. aureus, may be too low for protection.

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Population Pharmacokinetics of Amikacin in Adult Patients with Cystic Fibrosis [PublishAheadOfPrint]

Practitioners commonly use amikacin in patients with cystic fibrosis. Establishment of the pharmacokinetics of amikacin in adults with cystic fibrosis may increase the efficacy and safety of therapy. This study was aimed to establish the population pharmacokinetics of amikacin in adults with cystic fibrosis. We used serum concentration data obtained during routine therapeutic drug monitoring and explored the influence of patient covariates on drug disposition. We performed a retrospective chart review to collect amikacin dosing regimens, serum amikacin concentrations, blood sampling times, and patient's characteristics from adults with cystic fibrosis admitted for treatment of acute pulmonary exacerbations. Amikacin concentrations were retrospectively collected for 49 adults with cystic fibrosis, and 192 serum concentrations were available for analysis. A population pharmacokinetic model was developed using non-linear mixed effects modeling with first-order conditional estimation method. A two-compartment model with first-order elimination best-described amikacin pharmacokinetics. Creatinine clearance and weight were identified as significant covariates for CL and Vd, respectively, in the final model. Residual variability was modeled using a proportional error model. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 3.06 L/h, 14.4 L, 17.1 L and 0.925 L/h, respectively. The pharmacokinetics of amikacin in individuals with cystic fibrosis seems to differ compared with individuals without cystic fibrosis. However, further investigations are needed to confirm these results, and thus the need for variations in amikacin dosing. Future pharmacodynamic studies will potentially establish optimal amikacin dosing regimens for the treatment of acute pulmonary exacerbations in adult patients with CF.

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Characterization of mutations conferring resistance to rifampicin in Mycobacterium tuberculosis clinical strains [PublishAheadOfPrint]

Resistance of Mycobacterium tuberculosis to rifampicin, mediated by mutations in the rpoB gene, coding for the beta-subunit of RNA polymerase, poses a serious threat to the efficacy of clinical management and thus control programs of TB. The contribution of many individual rpoB mutations to the development and level of RMP resistance remains elusive. In this study, the incidence of mutations throughout the rpoB gene among 115 Mycobacterium tuberculosis clinical isolates, both resistant and susceptible to RMP was determined. Of the newly-discovered rpoB mutations, the role of three substitutions in the causation of RMP resistance was empirically tested. The results from in vitro mutagenesis experiments were combined with the assessment of the prevalence of rpoB mutations, and their reciprocal co-occurrences, across global M. tuberculosis populations.

Twenty-two different types of mutations in the rpoB gene were identified and distributed among 59 (90.8%) RMP-resistant strains. The minimum inhibitory concentrations (MICs) of RMP were within the range of 40-800 mg/L, with MIC50 and MIC90 values of 400 and 800 mg/L, respectively. None of the mutations (Gln429His, Met434Ile, Arg827Cys) inspected for their role in the development of RMP resistance produced a RMP-resistant phenotype in isogenic M. tuberculosis H37Rb strain-derived mutants. These mutations are supposed to compensate for fitness impairment incurred by other mutations directly associated with drug resistance.

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Impact of inducible blaDHA-1 on susceptibility of Klebsiella pneumoniae clinical isolates to LYS228 and identification of chromosomal mpl and ampD mutations mediating upregulation of plasmid borne blaDHA-1 expression [PublishAheadOfPrint]

Twenty three K. pneumoniae (bla_DHA-1) clinical isolates exhibited a range of susceptibilities to LYS228, with MICs of ≥8 μg/mL for 9 of these. Mutants with decreased susceptibility to LYS228 and upregulated expression of bla_DHA-1 were selected from representative isolates. These had mutations in the chromosomal peptidoglycan recycling genes mpl or ampD. Pre-existing mpl mutations were also found in some of the clinical isolates examined and these had strongly upregulated expression of bla_DHA-1.

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The monobactam LYS228: mode of action and mechanisms decreasing in vitro susceptibility of Escherichia coli and Klebsiella pneumoniae [PublishAheadOfPrint]

The monobactam scaffold is attractive for the development of new agents to treat infections caused by drug-resistant Gram-negative bacteria since it is stable to metallo-β-lactamases (MBLs). However, the clinically used monobactam aztreonam lacks stability to serine β-lactamases (SBLs) that are often co-expressed with MBLs. LYS228 is stable to MBLs and most SBLs. LYS228 bound purified Escherichia coli penicillin binding protein 3 (PBP3) similarly to aztreonam (k₂/K_d = 367504 s^-1M^-1 and 409229 s^-1M^-1, respectively) according to stopped-flow fluorimetry. A gel-based assay showed that LYS228 bound mainly to E. coli PBP3, with weaker binding to PBP1a and PBP1b. Exposing E. coli cells to LYS228 caused filamentation, consistent with impaired cell division. No single-step mutants were selected from twelve Enterobacteriaceae strains expressing different classes of β-lactamases at 8X the minimum inhibitory concentration (MIC) of LYS228 (frequency <2.5x10^-9). At 4X the MIC, mutants were selected from two of twelve strains at frequencies of 1.8x10^-7 and 4.2x10^-9. LYS228 MICs were ≤ 2 μg/mL against all mutants. These frequencies compared favorably to those for meropenem and tigecycline. Mutations decreasing LYS228 susceptibility occurred in ramR and cpxA (Klebsiella pneumoniae) and baeS (E. coli and K. pneumoniae). Susceptibility of E. coli ATCC 25922 to LYS228 decreased 256-fold (MIC 0.125 to 32 μg/mL) after 20 serial passages. Mutants accumulated mutations in ftsI (encoding the target, PBP3), baeR, acrD, envZ, sucB and rfaI. These results support the continued development of LYS228, which is currently undergoing Phase II clinical trials for complicated intraabdominal infection and complicated urinary tract infection (https://clinicaltrials.gov/ct2/show/NCT03377426; https://clinicaltrials.gov/ct2/show/NCT03354754).

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Absence of K13 Polymorphism in Plasmodium falciparum Parasites from Brazilian Endemic Areas. [PublishAheadOfPrint]

P. falciparum ART-resistant parasites can be evaluated examining polymorphisms in the Kelch (PfK13) domain. 69 samples from falciparum malaria patients were analyzed. All samples were from Brazilian endemic areas of the following states: Acre (n=14), Amapá (n=15), Amazonas (n=30) and Pará (n=10). After DNA alignment with the 3D7 reference sequence all samples were found to be wild-type. These data provide a baseline on PfK13 and reinforce the pertinence of ACTs treatment in Brazilian areas.

https://ift.tt/2mZ7vcA

Ceftazidime-Avibactam Susceptibility Breakpoints Against Enterobacteriaceae and Pseudomonas aeruginosa [PublishAheadOfPrint]

Clinical susceptibility breakpoints against Enterobacteriaceae and Pseudomonas aeruginosa for the ceftazidime-avibactam dosage regimen of 2000-500 mg every 8 hours (q8h) by 2-h intravenous infusion (adjusted for renal function) have been established by the FDA, CLSI and EUCAST as susceptible, MIC ≤8 mg/L, and resistant, MIC >8 mg/L. The key supportive data from PK/PD analyses, in vitro surveillance including molecular understanding of relevant resistance mechanisms, and efficacy in regulatory clinical trials, are collated and analyzed here.

https://ift.tt/2AnQFxk

Past and Present Perspectives on {beta}-Lactamases [PublishAheadOfPrint]

β-Lactamases, the major resistance determinant for β-lactam antibiotics in Gram-negative bacteria, are ancient enzymes whose origins can be traced back millions of years. These well-studied enzymes, currently numbering almost 2800 unique proteins, initially emerged from environmental sources, most likely to protect a producing bacterium from attack by naturally-occurring β-lactams. Their ancestors were presumably penicillin-binding proteins that share sequence homology with β-lactamases possessing an active site serine. Metallo-β-lactamases also exist, with one, or two, catalytically functional zinc ions. Although penicillinases in Gram-positive bacteria were reported shortly after penicillin was introduced clinically, transmissible β-lactamases that could hydrolyze recently-approved cephalosporins, monobactams and carbapenems later became important in Gram-negative pathogens. Nomenclature is based on one of two major systems. Originally, functional classifications were used, based on substrate and inhibitor profiles. A later scheme classifies β-lactamases according to amino acid sequences, resulting in class A, B, C and D enzymes. A more recent nomenclature combines the molecular and biochemical classifications into 17 functional groups that describe most β-lactamases. Some of the most problematic enzymes in the clinical community include extended-spectrum β-lactamases (ESBLs) and the serine and metallo-carbapenemases, all of which are at least partially addressed with new β-lactamase inhibitor combinations. New enzyme variants continue to be described, partly because of the ease of obtaining sequence data from whole genome sequencing studies. Often these new enzymes are devoid of any phenotypic descriptions, making it more difficult for clinicians and antibiotic researchers to address new challenges that may be posed by unusual β-lactamases.

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Antibiotic-induced dysbiosis predicts mortality in an animal model of Clostridium difficile infection [PublishAheadOfPrint]

Background

Antibiotic disruption of the intestinal microbiota favors colonization by Clostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis, and quantified the link between this intensity and mortality.

Methods

We administered either moxifloxacin (n=70) or clindamycin (n=60) to hamsters by subcutaneous injection from day 1 (D₁) to D₅, and challenged them with a C. difficile toxigenic strain at D₃. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D₀ and D₃ using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D₁₆. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time of C. difficile challenge and studied their capacity to predict subsequent death of the animals.

Results

Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (p<10^-5 for the change of Shannon index in moxifloxacin-treated animals and p<10^-9 in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the ROC curve of 0.89 [95%CI, 0.82;0.95] and 0.95 [0.90;0.98], respectively.

Conclusions

Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency to the DAV131A dose; mortality after C. difficile challenge was related to the intensity of dysbiosis in a similar manner with the two antibiotics.

https://ift.tt/2AqiYev

Extensive Genetic Commonality among Wildlife, Wastewater, Community, and Nosocomial Isolates of Escherichia coli Sequence Type 131 (H30R1 and H30Rx Subclones) That Carry blaCTX-M-27 or blaCTX-M-15 [PublishAheadOfPrint]

Escherichia coli sequence type 131 (ST131) is currently one of the leading causes of multi-drug-resistant extraintestinal infections globally. Here we analyzed the phenotypic and genotypic characteristics of 169 ST131 isolates from various sources (wildlife, wastewater, companion animals, community, and hospitals) to determine whether wildlife and the environment share similar strains with humans, supporting transmission of ST131 between different ecological niches. Susceptibility to 32 antimicrobials was tested by disc diffusion and broth microdilution. Antibiotic resistance genes, integrons, plasmid replicons, 52 virulence genes, and, fimH-based subtypes were detected by PCR and DNA sequencing. Genomic relatedness was determined by pulsed-field gel electrophoresis (PFGE). The genetic context and plasmid vs. chromosomal location of extended-spectrum beta-lactamase (ESBL) genes was determined by PCR and probe hybridization, respectively. The 169 ST131 study isolates segregated predominantly into bla_CTX-M-15H30Rx (60%) and bla_CTX-M-27H30R1 (25%) subclones. Within each subclone, isolates from different source groups were categorized into distinct PFGE clusters; genotypic characteristics were fairly well conserved within each major PFGE cluster. Irrespective of source, the bla_CTX-M-15H30Rx isolates typically exhibited virotype A (89%), an F2:A1:B- replicon (84%), and a 1.7 kb class 1 integron (92%), and had diverse structures upstream of the bla_CTX-M region. In contrast, the bla_CTX-M-27H30R1 isolates typically exhibited virotype C (86%), an F1:A2:B20 replicon (76%), and a conserved IS26-ISEcp1-bla_CTX-M-like structure. Despite considerable overall genetic diversity, our data demonstrate significant commonality between E. coli ST131 isolates from diverse environments, supporting transmission between different sources, including humans, environment, and wildlife.

https://ift.tt/2OtV7hd

In Vitro Activity of Isavuconazole versus Opportunistic Fungal Pathogens from Two Mycology Reference Laboratories [PublishAheadOfPrint]

Monitoring antifungal susceptibility patterns for new and established antifungal agents seems prudent given the increasing prevalence of uncommon species associated with higher antifungal resistance. We evaluated the activity of isavuconazole against 4,856 invasive yeasts and moulds collected worldwide.

The 4,856 clinical fungal isolates, including 2351 Candida spp. isolates, 97 non-Candida yeasts, 1,972 Aspergillus spp. isolates, and 361 non-Aspergillus moulds, including 292 Mucorales isolates collected in 2015-2016, were tested using CLSI methods.

The MIC values for isavuconazole versus Aspergillus ranged from 0.06 μg/ml to ≥16 μg/ml. The modal MIC for isavuconazole was 0.5 μg/ml (range 0.25 μg/ml [A. nidulans and A. terreus species complex] to 4 μg/ml [A. calidoustus and A. tubingensis]). Eight A. fumigatus isolates had elevated isavuconazole MIC values at ≥8 μg/ml (non-wild type). Isavuconazole showed comparable activity to itraconazole against the Mucorales. The lowest modal isavuconazole MIC values were seen for Rhizopus spp., R. arrhizus var. arrhizus, and R. microsporus (all 1 μg/ml). Candida spp. isolates were inhibited by ≤0.25 μg/ml of isavuconazole (range 96.1% [C. lusitaniae] to 100.0% [C. albicans, C. dubliniensis, C. kefyr, and C. orthopsilosis]). MIC values were ≤1 μg/ml for 95.5% of C. glabrata and for 100.0% of C. krusei. Isavuconazole was active against the non-Candida yeasts, including C. neoformans (100.0% at ≤0.5 μg/ml).

Isavuconazole exhibited excellent activity against most species of Candida and Aspergillus. Isavuconazole was comparable to posaconazole and voriconazole against the less common yeasts and moulds. Isavuconazole was generally less active than posaconazole and more active than voriconazole against the 292 Mucorales isolates. We confirm the potentially useful activity of isavuconazole against species of Rhizopus as determined by CLSI methods.

https://ift.tt/2ArzDOU

Development and validation of a phenotypic high-content imaging assay for assessing the antiviral activity of small-molecule inhibitors targeting the Zika virus [PublishAheadOfPrint]

Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barré syndrome. There are currently no drugs available to treat infection, and accordingly there is an unmet medical need for discovery of new therapies. High-throughput drug screening efforts focusing on indirect readouts of cell viability are prone to a higher frequency of false positives in cases where the virus is viable in the cell but the cytopathic effect is reduced or delayed. Here, we describe a fast and label-free phenotypic high-content imaging assay used to detect cells affected by the viral-induced cytopathic effect (CPE) using automated imaging and analysis. Protection from CPE correlates with a decrease in viral antigen production as observed by immunofluorescence. We trained our assay using a collection of nucleoside analogues against ZIKV; the previously reported antiviral activities of 2'-C-methylribonucleosides and ribavirin against the Zika virus in Vero cells were confirmed using our developed method. To validate the ability of our assay to reveal new anti-ZIKV compounds, we profiled a novel library of 24 natural product derivatives and found compound 1 as an inhibitor of ZIKV-induced cytopathic effect; activity of the compound was confirmed in human fetal neural stem cells (NSCs). The described technique can be easily leveraged as a primary screening assay for profiling large compound libraries against ZIKV, and can be expanded to other ZIKV strains and other cell lines displaying morphological changes upon ZIKV infection.

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Sensitivity of the C-terminal nuclease domain of Kaposi's sarcoma-associated herpesvirus ORF29 to two classes of active site ligands [PublishAheadOfPrint]

Kaposi's sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi's sarcoma, belongs to the Herpesviridae family, whose members employ a multicomponent terminase to resolve nonparametric viral DNA into genome-length units prior to their packaging. Homology modeling of ORF29 C-terminal nuclease domain (pORF29C) and bacteriophage Sf6 gp2 have suggested an active site clustered with four acidic residues, D⁴⁷⁶, E⁵⁵⁰, D⁶⁶¹ and D⁶⁶² that collectively sequester the catalytic divalent metal (Mn⁺⁺), and also provided important insight into a potential inhibitor binding mode. Using this model, we have expressed, purified and characterized the wild type pORF29C and variants substituted at the proposed active site residues. Differential scanning calorimetry demonstrated divalent metal-induced stabilization of WT and D⁶⁶¹A pORF29C, consistent with which these two enzymes exhibited Mn⁺⁺-dependent nuclease activity, although the latter mutant was significantly impaired. Thermal stability of WT and D⁶⁶¹A pORF29C was also enhanced by binding of an α-hydroxytropolone (α-HT) inhibitor shown to replace divalent metal at the active site. For the remaining mutants, thermal stability was unaffected by divalent metal or α-HT binding, supporting their role in catalysis. pORF29C nuclease activity was also inhibited by two classes of small molecules reported to inhibit HIV ribonuclease H and integrase, both of which belong to the superfamily of nucleotidyltransferases. Finally, α-HT inhibition of KSHV replication suggests ORF29 nuclease function as a potential antiviral target that could be combined with latency-activating compounds as a "shock-and-kill" antiviral strategy.

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Pooled Resistance Analysis in HCV Genotype 1-6 Infected Patients Treated With Glecaprevir/Pibrentasvir in Phase 2 and 3 Clinical Trials [PublishAheadOfPrint]

Over 2200 HCV genotype (GT)1-6 infected patients with or without cirrhosis who were treatment-naïve or experienced to interferon, ribavirin and/or sofosbuvir were treated with glecaprevir/pibrentasvir for 8, 12 or 16 weeks in 8 registrational phase 2/3 clinical studies. High SVR12 rates were achieved with <1% virologic failure (VF) rate. The prevalence of baseline polymorphisms (BP) in NS3 at amino acid positions 155 or 168 was low (<3%) in GT1, GT2, GT3, GT4, and GT6, while 41.9% of the GT5-infected patients had NS3-D168E; BPs were not detected at position 156 in NS3. The prevalence of NS5A-BPs was high across genotypes, driven by common polymorphisms at amino acid positions 30 or 31 in GT2, 58 in GT4, and 28 in GT6. The prevalence of NS5A T/Y93 polymorphisms was 5.5% in GT1, 4.9% in GT3, and 12.5% in GT6. Consistent with the activity of glecaprevir and pibrentasvir against most amino acid polymorphisms in vitro, BPs in NS3 and/or NS5A did not have an impact on treatment outcome for patients with GT1-6 infection, with the exception of treatment-experienced GT3-infected patients treated for 12 weeks, for whom a 16-week regimen of glecaprevir/pibrentasvir was required to achieve SVR12 rates ≥95%. Among the 22 patients experiencing VF, treatment-emergent substitutions were detected in NS3 in 50% and in NS5A in 82% of patients, frequently as a combination of substitutions that conferred resistance to glecaprevir and/or pibrentasvir. The glecaprevir/pibrentasvir regimen, when using the recommended durations, allows for a pangenotypic treatment option without the need for baseline resistance testing.

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Population Pharmacokinetic Analyses for Ertapenem in Subjects with a Wide Range of Body Sizes [PublishAheadOfPrint]

Despite a number of studies reporting that ertapenem pharmacokinetic parameters differ considerably in obese patients relative to healthy volunteers, functions describing the relationships between this agent's pharmacokinetics and indicators of body size have not been developed. The aim of this analysis was to develop an ertapenem population pharmacokinetic model using data from a previously-described study in normal weight, obese, and morbidly obese healthy volunteers. A single ertapenem 1 g dose administered intravenously was evaluated in 30 subjects within different body mass index (BMI) categories. The population pharmacokinetic model was developed using the first-order conditional estimation method with interaction (FOCE-I) algorithm within NONMEM. The ability of age, sex, renal function, and various body size measures (total body weight, height, body mass index, ideal body weight, fat-free mass, and body surface area [BSA]) to explain a portion of the interindividual variability on select PK parameters was explored using stepwise forward selection (α = 0.01) and backward elimination (α = 0.001). The data were best described using a linear three-compartment model with total-body weight as a covariate on clearance (CL=1.79·[Weight/95.90]^0.278) and BSA as a covariate on central volume (Vc=4.76·[BSA/2.06]^1.86). After accounting for fixed effects, the estimated interindividual variability was very low (<10% for all clearance and volume terms). Goodness-of-fit diagnostics indicated a precise and unbiased fit to the data. Using the developed population pharmacokinetic model and simulation, reliable estimates of ertapenem serum exposures, which can be utilized to evaluate various dosing regimens in subjects with a wide range of body sizes, are expected.

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Population pharmacokinetics of artemether, dihydroartemisinin and lumefantrine in Rwandese pregnant women treated for uncomplicated Plasmodium falciparum malaria [PublishAheadOfPrint]

The artemisinin-based combination therapy artemether-lumefantrine is commonly used in pregnant malaria patients. However, the effect of pregnancy-related changes on exposure is unclear and pregnancy has been associated with decreased efficacy in previous studies. This study aimed to characterize the population pharmacokinetics of artemether, its active metabolite dihydroartemisinin, and lumefantrine in 22 Rwandese pregnant women of second (n=11) and third trimester (n=11) with uncomplicated Plasmodium falciparum malaria.

These patients were enrolled from Rwamagana district hospital and received the standard fixed oral dose combination of 80 mg artemether and 480 mg lumefantrine twice daily for three days. Venous plasma concentrations were quantified for all three analytes using liquid chromatography coupled to tandem mass spectroscopy and data analyzed using nonlinear mixed-effects modelling.

Lumefantrine pharmacokinetics was described by a flexible but highly variable absorption, with a mean absorption time of 4.04 hours, followed by a bi-phasic disposition model. The median AUC_0- for lumefantrine was 641 h.mg/L. Model-based simulations indicated that 11.7% of the study population did not attain the target day 7 plasma concentration (280 ng/mL), a threshold associated with increased risk of recrudescence. Pharmacokinetics of artemether was time-dependent and the auto-induction of its clearance was described using an enzyme turnover model. The turnover half-life was predicted to be 30.4 hours. The typical oral clearance, which started at 475.7 L/hr, increased 1.43 fold at the end of treatment. Simulations suggested that lumefantrine pharmacokinetic target attainment appeared reassuring in Rwandese pregnant women, particularly compared to target attainment in Southeast Asia. Larger cohorts will be required to confirm this finding.

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Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae [PublishAheadOfPrint]

Resistance to colistin, a polypeptide drug used as an agent of last resort for treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria including carbapenem-resistant Enterobacteriaceae (CRE), severely limits treatment options and may even transform an XDR organism into one that is pan-resistant. We investigated the synergistic activity of colistin in combination with 19 antibiotics against a collection of 20 colistin-resistant Enterobacteriaceae isolates, 15 of which are also CRE. All combinations were tested against all strains using an inkjet printer-assisted digital dispensing checkerboard array, and those that demonstrated synergy by this method were evaluated against a single isolate in a time-kill synergy study. Eighteen of 19 combinations demonstrated synergy against two or more isolates, and the four most highly synergistic combinations (colistin combined with linezolid, rifampin, azithromycin, and fusidic acid) were synergistic against ≥90% of strains. Sixteen of 18 combinations (88.9%) that were synergistic in checkerboard array were also synergistic in a time-kill study. Our findings demonstrate that colistin in combination with a range of antibiotics, particularly protein and RNA synthesis inhibitors, exhibits synergy against colistin-resistant strains, suggesting that colistin may exert a subinhibitory permeabilizing effect on the Gram-negative outer membrane even in isolates that are resistant to it. These findings suggest that colistin combination therapy may have promise as a treatment approach for patients infected with colistin-resistant XDR Gram-negative pathogens.

https://ift.tt/2AsgyMI

Novel approaches to kill Toxoplasma by exploiting the uncontrolled uptake of unsaturated fatty acids and vulnerability to lipid storage inhibition of the parasite [PublishAheadOfPrint]

Toxoplasma gondii, an obligate intracellular parasite replicating in mammalian cells within a parasitophorous vacuole (PV), is an avid scavenger of lipids retrieved from the host cell. Following lipid uptake, this parasite stores excess lipids into lipid droplets (LD). Here, we examined the lipid storage capacities of Toxoplasma upon supplementation of the culture medium with various fatty acids at physiological concentrations. Supplemental unsaturated fatty acids (oleate (OA), palmitoleate, linoleate) accumulate in large LD and impair parasite replication whereas saturated fatty acids (palmitate, stearate) neither stimulate LD formation nor impact growth. Examination of parasite growth defects with 0.4 mM OA reveals massive lipid deposits outside LD, indicating enzymatic inadequacies for storing neutral lipids in LD in response to the copious salvage of OA. Toxoplasma exposure to 0.5 mM OA leads to irreversible growth arrest and lipid-induced damage, confirming a major disconnect between fatty acid uptake and the parasite's cellular lipid requirements. The importance of neutral lipid synthesis and storage to avoid lipotoxicity is further highlighted by the selective vulnerability of Toxoplasma, both the proliferative and the encysted forms, to subtoxic concentrations of the acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) pharmacological inhibitor T863. T863-treated parasites do not form LD, but instead build up large membranous structures within the cytoplasm, which suggests improper channeling and management of lipid excess. Dual addition of OA and T863 to infected cells intensifies the deterioration of the parasite. Overall, our data pinpoint Toxoplasma DGAT as a promising drug target against toxoplasmosis, without incurring risk of toxicity for mammalian cells.

https://ift.tt/2Ow29Cb

Low Meropenem Concentration in Brain-Dead Organ Donors: A Single-Center Pharmacokinetic Study and Simulation [PublishAheadOfPrint]

Meropenem is an ultrabroad-spectrum antibiotic of carbapenem family. In brain-dead organ donors, administration of standard meropenem dosages does not reach therapeutic levels. Our objectives were to determine the plasma concentration of meropenem after administration of standard meropenem dose and to estimate an improved dosage regimen for these patients. One gram of meropenem was administered as 1-h infusion every 8 h for 1–3 days, and blood samples were collected. The plasma concentration of meropenem was measured and subjected to pharmacokinetic analysis. Simcyp simulation was performed to predict the optimum plasma levels and dosage based on the patients' individual pharmacokinetic parameters. The maximum plasma concentration of meropenem was 3.29 μg/ml, which was lower than four times the minimum inhibitory concentration of 8 μg/ml. Although mean creatinine clearance of patients was moderately low (67.5 ml/min), apparent volume of distribution at steady state (V_ss) and time-averaged total body clearance (CL) of meropenem were markedly elevated (4.97 l/kg and 2.06 l/h/kg, respectively) owing to massive fluid loading to decrease the high sodium levels and to treat shock or dehydration. The simulation revealed that dose and infusion time of meropenem should be increased based on patients' V_ss and CL and loading dose is recommended to reach rapidly the target concentration. In conclusion, standard meropenem regimen is insufficient to achieve optimal drug levels in brain-dead patients and increase in dose and extended or continuous infusion with intravenous bolus administration of loading dose are recommended for these patients.

https://ift.tt/2Aql3qR

Does a single-dose preemptive intravenous ibuprofen have an effect on postoperative pain relief after septorhinoplasty?

Publication date: Available online 30 July 2018

Source: American Journal of Otolaryngology

Author(s): Mustafa Sitki Gozeler, Muhammed Sedat Sakat, Korhan Kilic, Ozgur Ozmen, Abdullah Can, Ilker Ince

Abstract

Purpose

Septorhinoplasty is a surgical procedure widely employed by otolaryngologists and plastic surgeons. The purpose of this study was to investigate the effects of a single pre-emptive dose of iv ibuprofen on postoperative pain and opioid consumption in patients undergoing septorhinoplasty.

Material and methods

50 patients scheduled for septorhinoplasty were included in this prospective, randomized, double-blinded study. Control group (n = 25) was administered 100 mL iv saline solution 30 min preoperatively, while Ibuprofen group (n = 26) received 800 mg ibuprofen iv. in 100 Ml saline solution. Intravenous fentanyl was administered with a Patient Controlled Analgesia device after surgery for postoperative pain management. Postoperative pain was evaluated using a Visual Analogue Scale (VAS) with 0 representing no pain and 10 the worst pain possible.

Results

VAS scores at 10, 20, and 30 min and at 1, 2, 4, 8, 12 and 24 h were lower in the ibuprofen group than in the control group (p < 0.05). Total fentanyl consumption was lower in the ibuprofen group compared to the placebo group (148.8 ± 86.4 mcq vs 338.00 ± 81.00 mcq), respectively.

Conclusion

We suggest that the pre-emptive use of iv ibuprofen at a dosage of 800 mg 30 min before septorhinoplasty will be beneficial in reducing opioid consumption and pain scores.

https://ift.tt/2Ov746f

Furazolidone‐containing triple and quadruple eradication therapy for initial treatment for Helicobacter pylori infection: A multicenter randomized controlled trial in China

Helicobacter, EarlyView.


https://ift.tt/2v84wTJ

Treatment of Sweet's syndrome in pregnancy

Dermatologic Therapy, EarlyView.


https://ift.tt/2v28KMj

Mohs micrographic surgery combined local flaps in treatment of EMPD: A retrospective case

Dermatologic Therapy, EarlyView.


https://ift.tt/2K7bYTD

Brimonidine tartrate gel plus topical steroid for the prevention of laser therapy‐related postinflammatory hyperpigmentation

Dermatologic Therapy, EarlyView.


https://ift.tt/2LQFa6i

Focal multimodality radiation therapy: A promising treatment for recalcitrant Darier disease

Dermatologic Therapy, EarlyView.


https://ift.tt/2K7bzAB

21st Chinese Society of Dermatology Annual Meeting, Hefei, Anhui, China

Dermatologic Therapy, EarlyView.


https://ift.tt/2v2UjYC

An enlightening tripartite event in Hanoi: Third Indochina Academy of Dermatology Conference, World Health Academy Dermatology Summit, and the Vietnamese Society of Dermatology Annual Meeting

Dermatologic Therapy, EarlyView.


https://ift.tt/2Kb25UR

A cost‐effective treatment model in dystrophic epidermolysis bullosa with congenital absence of skin

Dermatologic Therapy, EarlyView.


https://ift.tt/2LRuqo0

Assessing the association between subsistence strategies and the timing of weaning among indigenous archaeological populations of the Caribbean

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AngnST

Evidence of probable subadult scurvy in the Early Medieval cemetery of Castel Tirolo, South Tyrol, Italy

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ot9JgJ

Perinatal guanacos (Lama guanicoe) exploited by hunter‐gatherers from the Holocene of Argentine Pampas

International Journal of Osteoarchaeology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AqcJYf

Lingual lymph nodes in patients with squamous cell carcinoma of the tongue and the floor of the mouth

Head &Neck, EarlyView.


https://ift.tt/2M358QI

Oncologic outcomes with transoral robotic surgery for supraglottic squamous cell carcinoma: Results of the French Robotic Surgery Group of GETTEC

Head &Neck, EarlyView.


https://ift.tt/2LRgaM0

Sinonasal renal cell‐like adenocarcinoma: Easily misdiagnosed sinonasal tumor

Head &Neck, EarlyView.


https://ift.tt/2M34YJ6

Identification of lymphatic channels in the tracheoesophageal groove during central neck dissection for thyroid cancer

Head &Neck, EarlyView.


https://ift.tt/2LUA4pL

Pretreatment metabolic tumor volume as a prognostic factor in HPV‐associated oropharyngeal cancer in the context of AJCC 8th edition staging

Head &Neck, EarlyView.


https://ift.tt/2M40WjP

Radiotherapy for extranodal classic Hodgkin lymphoma of the maxillary sinus: Case report and literature review

Head &Neck, EarlyView.


https://ift.tt/2M7I0As

Forthcoming Meetings

Clinical &Experimental Allergy, Volume 48, Issue 8, Page 1073-1073, August 2018.


https://ift.tt/2M7DfH6

Issue Information

Clinical &Experimental Allergy, Volume 48, Issue 8, Page 907-909, August 2018.


https://ift.tt/2v1IEcz

Implementing primary prevention of food allergy in infants: New BSACI guidance published

Clinical &Experimental Allergy, Volume 48, Issue 8, Page 912-915, August 2018.


https://ift.tt/2LPdL4r

Best of the Other Journals

Clinical &Experimental Allergy, Volume 48, Issue 8, Page 1074-1074, August 2018.


https://ift.tt/2Kgs2CI

A summer's tale

Clinical &Experimental Allergy, Volume 48, Issue 8, Page 910-911, August 2018.


https://ift.tt/2v2BMvz

Cover Image

Clinical &Experimental Allergy, Volume 48, Issue 8, Page i-i, August 2018.


https://ift.tt/2K6NlXb

Tumstatin fragment selectively inhibits neutrophil infiltration in experimental asthma exacerbation

Clinical &Experimental Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M1peL7

Otogenic cerebral venous thrombosis in children: A review of 16 consecutive cases

Publication date: Available online 30 July 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Gil Coutinho, Sara Júlio, Ricardo Matos, Margarida Santos, Jorge Spratley

Abstract

Objectives

Management of otogenic cerebral venous thrombosis (OCVT) is controversial. Despite the modern antibiotic era OCVT still represents a potential life-threatening condition. This study aims to report the clinical presentation and management in a series of children with OCTV. The coexisting intracranial complications (ICC), the extent of the surgical treatment and the role of hypocoagulation were the analysed outcomes.

Material and Methods

Retrospective chart review of patients aged less than 16 years and consecutively treated for OCVT at a tertiary university hospital between January 2007 and March 2015.

Results

Sixteen children with ages ranging between 25 months to 16 years (9 girls/7 boys) with OCVT were identified. Acute otitis media was the causative factor in the majority of cases (n = 13). The remaining cases resulted from chronic otitis media with cholesteatoma (COMC). Eleven patients were under antibiotic therapy prior to admission. Other ICC were simultaneously present: intracranial abscess (n = 6); otitic hydrocephalus (n = 3); and meningitis (n = 1). Thrombus extension correlated with the presence of additional ICC (p = 0.035). Treatment in all cases comprised of broad-spectrum antibiotics, mastoidectomy, and long-range hypocoagulation with warfarin. Transtympanic ventilation tubes were inserted in all cases but one with COMC. Perioperative sigmoid sinus exposure was performed in seven patients, with drainage of perisinus empyema in three cases. Five children underwent simultaneous craniotomy for intracranial abscess drainage. Follow-up imaging performed in 12 cases revealed partial or complete recanalization in three and seven cases, respectively. After a mean hypocoagulation duration of nine months, no hemorrhagic or major neurologic complications were observed.

Conclusions

The clinical course of OCVT can be masked by previous antibiotic therapy. As such, a high suspicion index is needed for diagnosis. Simultaneous ICC appears to be more frequently found if an extensive thrombosis was present. The high recanalization rate in this series with low morbidity and no mortality can be obtained with a timely combination of antibiotics, mastoidectomy with transtympanic tube insertion and hypocoagulation. However, the decision to start hypocoagulation and its duration should be undertaken on an individual basis owing the possible adverse effects. Prospective and case-control studies are still needed to better clarify the role of the hypocoagulation treatment in OCVT.

https://ift.tt/2mXKXsE

Quality of life in the management of small vestibular schwannomas: observation, radiotherapy and microsurgery

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ka8eAw

Otitis Media with Effusion in Nasal Polyposis and Outcomes Following Surgery: a Longitudinal Observational Study

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v2HihI

Olfactory bulb neuroplasticity: A prospective cohort study in patients with chronic rhinosinusitis with nasal polyps

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ka7AD6

Findings on 7000 mri of the iam: To scan or not to scan? : A retrospective cohort study

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M0zPpS

Measuring otoplasty outcome: Expanding the validity to caregivers’ perspective and to Portuguese‐speaking children

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LADgXX

Issue Information

Clinical Otolaryngology, Volume 43, Issue 4, Page ii-v, August 2018.


https://ift.tt/2M2XoOM

Cover Image

Clinical Otolaryngology, Volume 43, Issue 4, Page i-i, August 2018.


https://ift.tt/2LACOZL

Author Guidelines

Clinical Otolaryngology, Volume 43, Issue 4, Page 1192-1193, August 2018.


https://ift.tt/2K78Reo

Efficacy of fibre‐optic laryngeal potassium titanyl phosphate laser surgery under local anaesthesia for the treatment of vocal polyps: A prospective study of 65 patients

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Lz4pdQ

Antibiotic prophylaxis in clean head and neck surgery: A prospective randomized controlled trial

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Kb6W8N

Clinical Outcomes of Exclusive Transcanal Endoscopic Tympanoplasty with Tragal Pericondrium in 129 Patients

Clinical Otolaryngology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M4eonK

The efficacy of hesperidin for treatment of acute otitis media

In this experimental study, the effect of hesperidin on the treatment of acute otitis media (AOM) was investigated in an AOM-induced rat model.

https://ift.tt/2mStIZM

Ménière’s disease with unremitting floating sensation is associated with canal paresis, gravity-sensitive dysfunction, mental illness, and bilaterality

The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease.

https://ift.tt/2K9eJUx

A new luminex‐based peptide assay to identify reactivity to baked, fermented and whole milk

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M09sQH

Gene Therapy for C1 Esterase Inhibitor Deficiency in a Murine Model of Hereditary Angioedema

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LP9f65

Staphylococcus aureus small colony variants: prevalence in chronic rhinosinusitis and induction by antibiotics

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M4v7HF

Hyper IgE in the Allergy Clinic‐ when is it Primary Immunodeficiency?

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LK0ASB

microRNA‐146a is linked to the production of IgE in mice but not in Atopic Dermatitis patients

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2K9ePeQ

Stability of Diluted Neuromuscular Blocking Agents Utilized in Perioperative Hypersensitivity Evaluation

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LK0lqF

Highlights of the 8th Drug Hypersensitivity Meeting: Amsterdam, April 19‐21, 2018

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M3kmW2

Japanese cedar pollinosis in Tokyo residents born after massive national afforestation policy

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v4u0RA

Efficacy and safety of SQ house dust mite sublingual immunotherapy‐tablet in Japanese children

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M1kViV

Comparing the different diagnostic criteria of Asthma‐COPD overlap

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v14DjP

Asthma diagnosis using integrated analysis of eosinophil microRNAs

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M1kNjr

Prevention of allergy by virus‐like nanoparticles (VNP) delivering shielded versions of major allergens in a humanized murine allergy model

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v14wop

Egg allergen specific IgE diversity predicts resolution of egg allergy in the population cohort HealthNuts

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M2W7qQ

Do mucosal biomarkers reveal the immunological state associated with food allergy?

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v14oFr

Protective effects of breastfeeding on respiratory symptoms in infants with 17q21 asthma risk variants

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M3SDEF

The soluble isoform of human FcɛRI is an endogenous inhibitor of IgE‐mediated mast cell responses

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v4tF1g

De novo sensitization to Aspergillus fumigatus in adult asthma over a 10‐year observation period

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2M6tNDV

The Health and Economic Outcomes of Early Egg Introduction Strategies

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LTWyXA

EAACI position paper on how to classify cutaneous manifestations of drug hypersensitivity

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2KbFxDk

Control of Allergic Rhinitis and Asthma Test (CARAT) with one‐week recall; validation of paper and electronic version

Allergy, Volume 0, Issue ja, -Not available-.


https://ift.tt/2v4tiDU

Characteristics and management of Asian skin

International Journal of Dermatology, EarlyView.


https://ift.tt/2viSu91

In situ and invasive melanoma in a high‐risk, New Zealand, population: A population‐based study

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2v2EiSp

A novel dermoscopic pattern observed in furuncular myiasis

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2KftYeq

The use of an innovative film‐forming topical gel in preventing Striae Gravidarum and treating Striae Distensae

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2LOkHPm

Multiple perianal ulcers due to suppositories

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2M7k3tq

Progress of an isolated collagenoma during pregnancy

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2LOkwDG

Unexpected positron emission tomography/computed tomography uptake in benign dermal naevus

Australasian Journal of Dermatology, EarlyView.


https://ift.tt/2Kftll4

Medicine and body image: resource planning for the poor. A memoir by Terence Ryan

International Journal of Dermatology, EarlyView.


https://ift.tt/2LDenuY

Retrospective analysis of a single‐center clinical experience toward development of curative treatment of 123 pemphigus patients with a long‐term follow‐up: efficacy and safety of the multidrug protocol combining intravenous immunoglobulin with the cytotoxic immunosuppressor and mitochondrion‐protecting drugs

International Journal of Dermatology, EarlyView.


https://ift.tt/2NUbNxg

Comments concerning “ALK positive primary cutaneous anaplastic large cell lymphoma: a case report and review of the literature”

International Journal of Dermatology, EarlyView.


https://ift.tt/2OsY01H

White and yellow dots as new trichoscopic signs of severe female androgenetic alopecia in dark skin phototypes

International Journal of Dermatology, EarlyView.


https://ift.tt/2vkUUUG

Chronic generalized pruritus without primary skin lesions: a longitudinal prospective observational study

International Journal of Dermatology, EarlyView.


https://ift.tt/2OqFk2y

Morphology, growth rate, and thickness of the nail plate during the pregnancy

International Journal of Dermatology, EarlyView.


https://ift.tt/2LBC6M6

An effective and promising treatment with adalimumab for impetigo herpetiformis with postpartum flare‐up

International Journal of Dermatology, EarlyView.


https://ift.tt/2NSWR2r

A study on gender differences in newly detected leprosy cases in Sichuan, China, 2000–2015

International Journal of Dermatology, EarlyView.


https://ift.tt/2LFY0xP

Clinical management of Anti‐TNF‐alpha‐induced psoriasis or psoriasiform lesions in inflammatory bowel disease patients: a systematic review

International Journal of Dermatology, EarlyView.


https://ift.tt/2vkUFce

Productivity changes following medical and surgical treatment of chronic rhinosinusitis by symptom domain

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2AopthZ

Effects of decongestant addition to intranasal corticosteroid for chronic rhinitis: a systematic review and meta‐analysis

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2LLajI5

Risk factors and strategies in nonadherence with subcutaneous immunotherapy: a real‐life study

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2AngQ7k

Nitric oxide‐releasing microparticles as a potent antimicrobial therapeutic against chronic rhinosinusitis bacterial isolates

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2v4ou1k

Reliability and validity of the Korean version of the Questionnaire of Olfactory Disorders

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2M4oCof

Sex bias in rhinology research

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2LQlsYm

Additional options in chronic rhinosinusitis management

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2M0vFOM

Tissue changes over time after polydioxanone thread insertion: An animal study with pigs

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2Ou5CRu

Topography of the dorsal nasal artery and its clinical implications for augmentation of the dorsum of the nose

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2Asp12o

A red pumpkin seed extract reduces melanosome transfer to keratinocytes by activation of Nrf2 signaling

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2mWdGy5

Applications and efficacy of platelet‐rich plasma in dermatology: A clinical review

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2AwngBs

Perspectives in cosmetic dermatology: What is in front of the mirror?

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2mUvzx3

Assessment of the moisturizing properties of a magnetic mask containing iron oxide particles

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2ArH0Gg

Comparison of three strip harvesting technqiues (Haber's, Pathomvanich's and Ahmad's techniques)

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2OvuCrI

Identification and integrated analysis of microRNA expression profiles in keloid

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2AwmZyq

Lipoma removal using a high‐frequency ultrasound‐guided injection of a Class III CE‐marked device—Empirical findings

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2mXoqw8

Antiaging efficacy of a retinaldehyde‐based cream compared with glycolic acid peel sessions: A randomized controlled study

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2Ar13oa

Oral propranolol for infantile hemangiomas beyond the proliferative phase

The Journal of Dermatology, EarlyView.


https://ift.tt/2Ovecj2

Rapid alteration of serum interleukin‐6 levels may predict the reactivity of i.v. cyclophosphamide pulse therapy in systemic sclerosis‐associated interstitial lung disease

The Journal of Dermatology, EarlyView.


https://ift.tt/2ApM25T

Increase in antinuclear antibody levels through biologic treatment for psoriasis

The Journal of Dermatology, EarlyView.


https://ift.tt/2mUvoln

Urticarial vasculitis and subcutaneous nodules in the extremities seen in a patient with mucopolysaccharidosis II after hematopoietic stem cell therapy

The Journal of Dermatology, EarlyView.


https://ift.tt/2AlwqjU

Indeterminate cell histiocytosis presenting as a single nodule of the nose

The Journal of Dermatology, EarlyView.


https://ift.tt/2OvubO6

Undifferentiated pleomorphic sarcoma in a patient with Cowden syndrome after radiotherapy for breast cancer

The Journal of Dermatology, EarlyView.


https://ift.tt/2Ar0Z7U

Characteristics of multiple basal cell carcinomas: The first study on Japanese patients

The Journal of Dermatology, EarlyView.


https://ift.tt/2Ovu2Ky

Effectiveness of etretinate/yokuinin combination therapy for lip squamous cell carcinoma

The Journal of Dermatology, EarlyView.


https://ift.tt/2Ar0Pxk

Azathioprine‐induced myelosuppression in two pemphigus vulgaris patients with homozygous polymorphism of NUDT15

The Journal of Dermatology, EarlyView.


https://ift.tt/2OvQtiz

Cutis laxa for diagnosis of γ1‐heavy‐chain deposition disease: Report of four cases

The Journal of Dermatology, EarlyView.


https://ift.tt/2Ama1Di

Skin sensitivity and skin microbiota: Is there a link?

Experimental Dermatology, EarlyView.


https://ift.tt/2AnG9WV

Serum Level of IL‐4 Predicts Response to Topical Immunotherapy with Diphenylcyclopropenone (DPCP) in Alopecia Areata

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OuauGs

UVB‐inhibited H19 activates the melanogenesis axis by paracrine effects

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AqABuX

RIP4 upregulates CCL20 expression through STAT3 signaling in cultured keratinocytes

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mXy8P2

SIG1459: A novel phytyl‐cysteine derived TLR2 modulator with in vitro and clinical anti‐acne activity

Experimental Dermatology, EarlyView.


https://ift.tt/2AqAtvt

Loss of Gata6 causes dilation of the hair follicle canal and sebaceous duct

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ou5gKE

Corneocyte Proteomics: Applications to Skin Biology and Dermatology

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AqAjUT

Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mXxqBm

Dissociated Skin Cells Regenerate Hair Follicles in a MicroWound, “The Punch Assay”

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AqA7F9

Ex‐vivo fluorescence confocal microscopy for intraoperative, real time diagnoses of cutaneous inflammatory diseases: a preliminary study

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2OvTY90

Inactivation of autophagy leads to changes in sebaceous gland morphology and function

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2AqzRWH

A dipeptidyl peptidase‐4 inhibitor promotes wound healing in normoglycemic mice by modulating keratinocyte activity

Experimental Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mXnnfG

Clinical Thyroidology®High-Impact Articles

FREE ACCESS through August 13, 2018.
Read Now:

Higher Preconception Maternal Iodine Intakes Are Associated with Higher Child IQ
Elizabeth N. Pearce 

Some Advanced Thyroid Cancer Patients Have a Prolonged Response to Lenvatinib
Brian W. Kim

Analysis of Clinical Factors 1 Year After Surgery for Thyroid Cancer Enables Prediction of Treatment-free Survival
Jerome M. Hershman 

New Genomic Sequencing Classifier in Cytologically Indeterminate Thyroid Nodules Shows Improved Results
Stephanie Fish

 

 

The post Clinical Thyroidology^®High-Impact Articles appeared first on American Thyroid Association.

https://ift.tt/2KaH4db

Relapse rates in patients with unilesional primary cutaneous B‐cell lymphoma treated with radiation therapy: a single‐institution experience

British Journal of Dermatology, EarlyView.


https://ift.tt/2vm7yCT

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population‐based Janus Cohort

British Journal of Dermatology, EarlyView.


https://ift.tt/2LAkGPQ

Patient preferences for topical treatment of actinic keratoses: a discrete‐choice experiment

British Journal of Dermatology, EarlyView.


https://ift.tt/2vkBTSt

Impact of anti‐interleukin‐17 treatment on cutaneous and genital human papillomavirus infection

British Journal of Dermatology, EarlyView.


https://ift.tt/2LAkFeK

Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4‐aminoquinoline antimalarials: a meta‐analysis

British Journal of Dermatology, EarlyView.


https://ift.tt/2vlbZOn

The widespread use of topical antimicrobials enriches for resistance in Staphylococcus aureus isolated from patients with atopic dermatitis

British Journal of Dermatology, EarlyView.


https://ift.tt/2LyIe7A

Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta‐analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland

British Journal of Dermatology, EarlyView.


https://ift.tt/2vk2PSi

Is melanoma mortality declining in Spain? Analysis of trends from 1975 to 2016

British Journal of Dermatology, EarlyView.


https://ift.tt/2LEpxiO

Pembrolizumab‐associated mucous membrane pemphigoid in a patient with Merkel cell carcinoma

British Journal of Dermatology, EarlyView.


https://ift.tt/2vrk3xh

Evaluation of the reliability and validity of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) in pediatric cutaneous lupus among pediatric dermatologists and rheumatologists

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2Ou2xko

Efficacy and safety of ixekizumab in a randomized, double‐blinded, placebo‐controlled phase IIIb study of patients with moderate‐to‐severe genital psoriasis

British Journal of Dermatology, EarlyView.


https://ift.tt/2vevMiq

Risk of skin cancer in people with vitiligo: a systematic review and meta‐analysis

British Journal of Dermatology, EarlyView.


https://ift.tt/2Ou2mWg

International Initiative for outcomes (INFO) for vitiligo: Workshops with vitiligo patients on repigmentation

British Journal of Dermatology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2vlbWCb

Correlation of psoriasis activity with socioeconomic status: cross‐sectional analysis of patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR)

British Journal of Dermatology, EarlyView.


https://ift.tt/2LBgWgY

Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin and pristinamycin: clinical history and patch testing

British Journal of Dermatology, EarlyView.


https://ift.tt/2vevfNs

Effective sirolimus treatment for refractory spindle cell haemangioma

British Journal of Dermatology, EarlyView.


https://ift.tt/2LAcTBr

Oral ulcers as a presentation of secondary syphilis

Clinical and Experimental Dermatology, EarlyView.


https://ift.tt/2LCQN1q

Tildrakizumab Gets EMA Panel Nod for Plaque Psoriasis

A European Medicines Agency panel has recommended tildrakizumab for the treatment of moderate to severe plaque psoriasis.
International Approvals

https://ift.tt/2NXCeC2

Tasks, competences and educational needs of dermatology health care providers in the public and private sectors.results of the EADV‐NWAG survey in Belgium

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mThfVD

The use of prp (platelet‐rich plasma) in patients affected by genital lichen sclerosus: clinical analysis and results

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2KaALGj

Polymorphisms in melanocortin system and MYG1 genes are associated with vitiligo

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mTgYC5

Lichen planus pigmentosus inversus in a Finnish man

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2KbDu2i

Incidence and characteristics of thick second primary melanomas. A study of the German Central Malignant Melanoma Registry

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mUAWwn

An original exploration of genital lichen sclerosus: the semantic connectivity map

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2K6bWeJ

Enhancing survival of Demodex mites in vitro

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2LAaZAS

Immune‐regulatory genes as possible modifiers of familial pityriasis rubra pilaris – lessons from a family with PRP and psoriasis

Journal of the European Academy of Dermatology and Venereology, EarlyView.


https://ift.tt/2KbD4ZM

Patients’ needs and psoriasis treatment

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2mRAK0K

8% Capsaicin ‐ a hot medicine for neuropathic itch

Journal of the European Academy of Dermatology and Venereology, Volume 0, Issue ja, -Not available-.


https://ift.tt/2K8RIB4

Forthcoming Events

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1391-1391, August 2018.


https://ift.tt/2LyxHcJ

RASopathic comedone‐like or cystic lesions induced by vemurafenib: a model of skin lesions similar but not identical to those induced by dioxins MADISH

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1368-1372, August 2018.


https://ift.tt/2KabLih

Characterizing clinicopathological and immunohistochemical findings in dermatomyositis panniculitis

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1231-1232, August 2018.


https://ift.tt/2mWOirX

Issue Information

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1225-1230, August 2018.


https://ift.tt/2Kb2B59

Pioneers in dermatology and venereology: An interview with Prof. Jose Maria Mascaro

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1235-1237, August 2018.


https://ift.tt/2LAhzr8

Aryl hydrocarbon receptor signalling in the skin and adverse vemurafenib effects

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1233-1234, August 2018.


https://ift.tt/2KaAh2X

Announcement

Journal of the European Academy of Dermatology and Venereology, Volume 32, Issue 8, Page 1392-1392, August 2018.


https://ift.tt/2mUxh1l

Adverse events associated with apremilast use and withdrawal for psoriasis in a real‐world setting

Journal of the European Academy of Dermatology and Venereology, EarlyView.


https://ift.tt/2KaxpDr

CD8+ Cytotoxic T Lymphocyte Responses and Viral Epitope Escape in Acute HIV-1 Infection

Viral Immunology, Ahead of Print.


https://ift.tt/2NZeMEP

Maxillary sinusitis complicated by stroke

Publication date: Available online 30 July 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): C. Fabre, I. Atallah, I. Wroblewski, C.A. Righini

Abstract

Introduction

Neurological complications of acute sinusitis are exceptional, but potentially serious.

Case report

The authors report the case of a 6-year-old diabetic girl who presented with middle cerebral artery ischemic stroke secondary to inflammatory arteritis of the left internal carotid artery in a context of bilateral acute maxillary sinusitis. MRI confirmed ischaemic stroke associated with carotid arteritis and complete obstruction of the maxillary sinuses. A favourable outcome was observed after endoscopic drainage of the sinuses associated with broad-spectrum antibiotic therapy.

Discussion

This complication was probably due to spread of an infectious inflammatory reaction of the intrapetrosal carotid artery and its branches via the pterygoid venous plexus. To our knowledge, this is the first published case report of maxillary sinusitis complicated by stroke.

https://ift.tt/2vn9NGi

Reconstruction of the anterior wall of the frontal sinus by a custom-made titanium prosthesis after resection of a giant osteoma of the frontal sinus

Publication date: Available online 30 July 2018

Source: European Annals of Otorhinolaryngology, Head and Neck Diseases

Author(s): J. Fanchette, B. Faucon, F. Cartry, M. Ratajczak

Abstract

Osteoma is a benign, usually asymptomatic bone tumour, frequently arising in the nose and paranasal sinuses. Surgical treatment is required when the patient becomes symptomatic or presents ophthalmological or neurological complications. Although an endoscopic approach is increasingly used, depending on the size and site of the osteoma, open surgery may be preferable and remains the standard treatment. This technical note describes a case of giant osteoma of the frontal sinus that required a bicoronal approach with reconstruction by a custom-made titanium prosthesis.

https://ift.tt/2Oqcm2O

“The changing face of anaphylaxis in adults and adolescents”

Publication date: Available online 30 July 2018

Source: Annals of Allergy, Asthma & Immunology

Author(s): Debendra Pattanaik, Phil Lieberman, Jay Lieberman, Thanai Pongdee, Alexandria Tran Keene

Abstract

Background

Our institution has published serial studies of adults and adolescents experiencing anaphylactic events. The first series was published in 1993 and the last in 2006. It was our perception that the nature of anaphylactic episodes had changed over the two decades since the last review.

Objective

To determine whether the etiologies and presentations of anaphylaxis has changed over the last decade in our population.

Methods

Patient charts were identified based upon ICD-9 codes for anaphylactic shock. Charts identified were analyzed for clinical symptoms reported, comorbidities, etiology, investigative testing, and subsequent treatment. These cases were categorized as definitive, probable, or idiopathic based on history and results from testing, similar to our prior reports.

Results

We identified 281 possible cases, of which 218 met criteria for anaphylaxis. Among the cases, median age was 42 years (range 9-78) and 64% were female. In the review of cases, 85 (39%) were determined to have a definitive etiology, 57 a probable etiology (26%), and 76 (35%) were idiopathic. Interestingly, among those with a definitive cause, the most common etiology identified was galactose-alpha-1,3-galactose (α- gal), accounting for 28 cases (33%). Foods were the 2nd leading cause accounting for 24 cases (28%).

Conclusion

In this follow up report on anaphylaxis etiology from a single center, the most common etiology was α-gal. This varies greatly from the prior reports our center. Interestingly, the percent of cases attributed to idiopathic anaphylaxis decreased from 59% in our past report to 35% in this report, which could largely be explained by the number of α-gal cases.

https://ift.tt/2LTS4R7

Searching for crab-borne antimicrobial peptides: Crustin from Portunus pelagicus triggers biofilm inhibition and immune responses of Artemia salina against GFP tagged Vibrio parahaemolyticus Dahv2

Publication date: September 2018

Source: Molecular Immunology, Volume 101

Author(s): Ravichandran Rekha, Baskaralingam Vaseeharan, Ramachandran Ishwarya, Mahalingam Anjugam, Naiyf S. Alharbi, Shine Kadaikunnan, Jamal M. Khaled, Mohammed N. Al-anbr, Marimuthu Govindarajan

Abstract

Marine organisms represent a huge source of novel compounds for the development of effective antimicrobial drugs. The present study focus on the purification of the antimicrobial peptide crustin from the haemolymph of the blue swimmer crab, Portunus pelagicus, by blue Sepharose CL-6B matrix assisted affinity column chromatography. Crustin showed a single band with a molecular mass of 17 kDa in SDS-PAGE analysis. The XRD analysis exhibited peaks at 32° and 45° while a distinct peak with a retention time of 1.8 min resulted in high performance liquid chromatography (HPLC) pointing out the crystalline nature and purity of crustin, respectively. Crustin purified from P. pelagicus (Pp-Cru) showed immunological activities, triggering encapsulation, phagocytosis on Sepharose beads and yeast (Saccharomyces cerevisiae) respectively. Furthermore, encapsulation of GFP tagged V. parahaemolyticus in Artemia salina and challenging study were assessed under CLSM and the potential of Pp-Cru was examined in vivo. In addition, the growth reduction and biofilm inhibition potential of Pp-Cru on Staphylococcus aureus, Enterococcus faecalis (Gram- positive bacteria) and Pseudomonas aeruginosa, Escherichia coli (Gram-negative bacteria) was evidenced by inverted and confocal laser scanning microscopic analysis, revealing that 100 μg/ml of Pp-Cru can disrupt the biofilm matrix thereby the thickness of biofilm was significantly reduced. Overall, the present investigation might provide a sensitive platform to realize the significant function of Pp-Cru in crustacean immune mechanism as well as its potential to bacterial growth inhibitor. The functional properties of purified Pp-Cru antimicrobial peptide may lead to a superior understanding of innate immune response in P. pelagicus species, which suggest the promising application for drug development in aquaculture.

Graphical abstract

https://ift.tt/2AotUtr

Letter to the editor: “Sentinel node biopsy in early oral squamous cell carcinomas: Long-term follow-up and nodal failure analysis”

Publication date: Available online 30 July 2018

Source: Oral Oncology

Author(s): Tao Wang, Longjiang Li

https://ift.tt/2v0fkms

Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene

Publication date: Available online 30 July 2018

Source: Allergologia et Immunopathologia

Author(s): D. Doğruel, M. Serbes, A.Ş. Şaşihüseyinoğlu, M. Yılmaz, D.U. Altıntaş, A. Bişgin

Abstract

Background

X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA.

Methods

Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively.

Results

We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype.

Conclusions

Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

https://ift.tt/2M3vr9t

Ménière’s disease with unremitting floating sensation is associated with canal paresis, gravity-sensitive dysfunction, mental illness, and bilaterality

Publication date: Available online 30 July 2018

Source: Auris Nasus Larynx

Author(s): Tadashi Kitahara, Masaharu Sakagami, Taeko Ito, Tomoyuki Shiozaki, Koichi Kitano, Akinori Yamashita, Ichiro Ota, Yoshiro Wada, Toshiaki Yamanaka

Abstract

Objective

The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease.

Methods

We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3–6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3–6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range.

Results

The ratios (+) were as follows: C-test = 33.3% (20/60), cVEMP = 25.0% (15/60), SVV = 50.0% (30/60), G-test = 55.0% (33/60), ECoG = 63.3% (38/60), ieMRI = 86.7% (52/60), ADH = 35.0% (21/60), BAP = 11.7% (7/60), and SDS = 40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones.

Conclusions

Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments.

https://ift.tt/2mZpO1n

The efficacy of hesperidin for treatment of acute otitis media

Publication date: Available online 30 July 2018

Source: Auris Nasus Larynx

Author(s): Erdem Atalay Cetinkaya, Osman Ciftci, Saadet Alan, M. Namık Oztanır, Nese Basak

Abstract

Objectives

In this experimental study, the effect of hesperidin on the treatment of acute otitis media (AOM) was investigated in an AOM-induced rat model.

Methods

In total, 35 rats were randomly divided into the following five groups (n = 7): group 1 (control), group 2 (AOM with no treatment), group 3 (AOM + antibiotic), group 4 (AOM + hesperidin), and group 5 (AOM + hesperidin + antibiotic). On day 14, group 3,4 and 5 rats were given antibiotic and hesperidin via gavages, respectively. Histopathological and immunological analyses were performed and the results analyzed.

Results

Serum levels of TNF-α, IL-4, IL-6 and IL-1β were significantly decreased in the hesperidin- and antibiotic-treated groups compared to the AOM group. The AOM + antibiotic and AOM + hesperidin groups demonstrated reduced histological damage compared to the AOM group. Between the AOM + antibiotic and AOM + hesperidin groups, significant differences in tympanic membrane thickness(ThicTM), inflammation(Inf), and sclerosis(Sc) values were observed. However, no difference in epithelial damage(DamEpith), was seen between the two groups. There was a significant difference in the AOM + antibiotic and AOM + antibiotic + hesperidin groups compared to AOM group (P < 0.001).

Conclusions

In this study, we observed that both antibiotic and hesperidin treatment reduced AOM symptoms in an AOM-induced rat model. The values in AOM + antibiotic + hesperidin group were markedly lower than those of the other groups. From our results, we propose that hesperidin, in combination with antibiotics, may provide a successful alternative treatment for AOM compared with antibiotics used alone.

https://ift.tt/2AoUqTl

Prophylaxe des Vulva- und des Vaginalkarzinoms und ihrer Vorstufen

Zusammenfassung

Hintergrund

Vulva- und Vaginalkarzinome sind zunehmend diagnostizierte Tumorentitäten in Deutschland. Vulva- und Vaginalkarzinome entstehen über zwei unterschiedliche pathogenetische Mechanismen: Zum einen kann eine persistierende Infektion mit dem humanen Papillomvirus (HPV, v. a. Typ 16, 31, 33) über eine undifferenzierte vulväre/vaginale intraepitheliale Neoplasie (VIN/VAIN) zum invasiven Vulva‑/Vaginalkarzinom führen. Diese Tumoren finden sich eher bei jüngeren Frauen. Davon abzugrenzen ist das Vulvakarzinom der älteren Frauen, das auf dem Boden einer chronischen Hauterkrankung (z. B. Lichen sclerosus et atrophicus, LSA) über Mutationen im Tumorsuppressorgen p53 entsteht. Auch beim Vaginalkarzinom ist einer der Risikofaktoren ein Lichen sclerosus oder Lichen planus, diese Tumoren sind HPV-negativ. Daneben gibt es eine ganze Reihe von Tumoren, deren Ursache nicht bekannt ist.

Fragestellung

Gibt es primäre oder sekundäre Präventionsmaßnahmen, die die Entstehung dieser Tumoren verhindern können?

Ergebnisse

Die HPV-induzierten Vulva- und Vaginalkarzinome können zu einem bedeutenden Teil durch eine HPV-Impfung von HPV-naiven Frauen primär verhindert werden. Der nonavalente Impfstoff deckt die relevanten HPV-Typen 16, (18), 31 und 33 mit einer Wirksamkeit von 97 % ab, der bivalente Impfstoff hat eine vergleichbar hohe Effektivität aber nur für HPV16 und HPV18.

Ob das licheninduzierte Vulva‑/Vaginalkarzinom durch eine konsequente lokale Dauertherapie mit Kortison oder Calcineurininhibitoren primär präventiv verhindert werden kann wird diskutiert. Erste Daten, die darauf hindeuten, liegen vor.

https://ift.tt/2v2g0Ib

Bildgeführte radiologische Interventionen beim HCC

Zusammenfassung

Hintergrund

Bildgeführte Interventionen wie Radiofrequenz- oder Mikrowellenablation, CT-gesteuerte Brachytherapie oder Stereotaxie (SBRT), Chemoembolisation oder Yttrium-90(⁹⁰Y)-Radioembolisation sind Teil aktueller Leitlinien zur Therapie des hepatozellulären Karzinoms (HCC) und unterliegen beständiger Validierung in aktuellen klinischen Studien.

Ziel

Dieser Artikel gibt einen Überblick über den aktuellen Stand der Evidenz und Leitlinienempfehlungen zu den genannten radiologischen, nuklearmedizinischen oder auch strahlentherapeutischen Verfahren.

Ergebnisse

Sowohl lokale Tumorablationen als auch die lokoregionäre Chemoembolisation sind Teil aller wesentlichen Leitlinien zur Behandlung des HCC. Die bildgeführten Tumorablationen im Stadium BCLC A oder auch BCLC 0 stellen sich mittlerweile als gleichwertige Alternative zur chirurgischen Resektion dar, wenn die Patientenselektion entsprechend adaptiert wird. Als lokoregionäre Therapie ist die Chemoembolisation im Stadium BCLC B bei gut erhaltener Leberfunktion und begrenzter Tumorlast Therapiestandard. Zum Einsatz der ⁹⁰Y-Radioembolisation liegen bei BCLC B keine randomisierten Daten vor. Für BCLC C-Patienten ist die Chemoembolisation nicht indiziert. Als Alternativtherapie bei Systemtherapieversagen oder Kontraindikation für Sorafenib, aber auch mit Blick auf die deutlich verbesserte Verträglichkeit gegenüber Sorafenib kann die ⁹⁰Y-Radioembolisation erwogen werden.

https://ift.tt/2M2qUE8

Update zu uterinen Sarkomen

Zusammenfassung

Uterine Sarkome bilden eine inhomogene Gruppe seltener Tumoren der Uterusmuskulatur. Es sind meist aggressive Neoplasien, die vom uterinen Bindegewebe oder vom endometrialen Stroma ausgehen. Histologisch werden folgende Subtypen unterschieden: das Leiomyosarkom (LMS), das low-grade endometriale Stromasarkom (LG-ESS) und das high-grade endometriale Stromasarkom (HG-ESS) sowie das undifferenzierte Stromasarkom (UES). Die Inzidenz liegt bei 0,5–3,3 pro 100.000 Frauen pro Jahr; insgesamt bilden sie mit 1–2 % nur einen kleinen Anteil der uterinen Malignome. Eine andere Kategorie bilden uterine Sarkome gemischten Ursprungs, wie Adenosarkome, Karzinosarkome (maligne Müller-Mischtumoren) und andere heterologe Sarkome (z. B. Chondrosarkome, Liposarkome, Fibrosarkome etc.). Im Beitrag wird auf das spezifische Management der häufigen Entitäten (LMS, LG-ESS, HG-ESS und UES) Bezug genommen. Im August 2015 wurde die erste Version einer S2k-Leitlinie zu uterinen Sarkomen herausgegeben.

https://ift.tt/2uZR5EY

Verhaltensstörung oder Schmerz?

Zusammenfassung

Hintergrund

Bei Menschen mit geistiger Beeinträchtigung werden Schmerzen zu selten und zu spät diagnostiziert. Diese Patienten erhalten trotz größerer Krankheitslast wesentlich weniger Schmerzmittel als Menschen ohne Behinderung.

Ergebnisse

An die Möglichkeit des Vorliegens von Schmerzen zu denken, ist dabei genauso entscheidend wie eine adäquate und sensible Diagnostik. Neben der Nutzung aller Mittel zur Verbesserung der Kommunikation (Erklärungen in leichter Sprache, Arbeiten mit Bildern und Symbolen) ist die Fremdauskunft zusätzlich oder ersatzweise häufig unverzichtbar (Befragung von Nahestehenden, spezielle Assessment-Instrumente). Jede Veränderung des Verhaltens muss als mögliche Ursache von Schmerzen (oder anderen Symptomen) aufmerksam registriert und weiter abgeklärt werden.

Schlussfolgerung

Die Schmerztherapie kann und sollte grundsätzlich wie bei nichtbehinderten Menschen durchgeführt werden, nichtmedikamentöse Maßnahmen stehen dabei im Vordergrund. Die Medikamentengabe sollte wie bei alten Menschen niedrig begonnen und nur langsam gesteigert werden. Mit häufigerem Einsatz von – ggf. auch probatorischer – Schmerztherapie lassen sich viele sog. Verhaltensstörungen adäquat und besser als mit Psychopharmaka behandeln.

https://ift.tt/2M30ySx

HOXB13 is not expressed in pleomorphic giant cell carcinoma of the bladder

https://ift.tt/2K7S1Mr

Reply to the letter “How to standardize the evaluation of tumor regression grading of gastrointestinal cancers after neoadjuvant therapy?” by Dr. Nasierowska-Guttmejer and Dr. Szawlowski, VIAR-D-18-00181

https://ift.tt/2LLBse4

Letter to the editor: reply to Valeria Barresi “HOXB13 is not expressed in pleomorphic giant cell carcinoma of the bladder”

https://ift.tt/2NUN3Vu

In this issue

https://ift.tt/2v0p0xs

A case of multiple familial trichoepitheliomas responding to treatment with the Hedgehog signaling pathway inhibitor vismodegib

Abstract

Multiple familial trichoepitheliomas (MFT) is an autosomal dominantly inherited disease characterized by multiple skin appendage tumors. We describe a patient showing a continuous spectrum of follicular differentiated neoplasms including classical trichoepitheliomas but also infiltrative growing and finally metastasizing malignant follicular differentiated tumors. Germline mutation analysis revealed a nonsense mutation in the cylindromatosis (CYLD) gene. Gene expression analysis by real-time PCR of tumor tissue showed overexpression of glioma-associated oncogene Gli1 mRNA. Treatment with the Hedgehog pathway inhibitor vismodegib resulted in a significant regression of the highly differentiated trichoepitheliomas. Gli upregulation is indicative of an active Hedgehog signaling pathway. We hypothesize that its upregulation is indirectly caused by CYLD mutation which promotes tumor development. Vismodegib treatment could thus provide a new treatment option for patients with this debilitating disorder.

https://ift.tt/2M1KFvP

Neuroendocrine tumor of the pancreas with rhabdoid feature

Abstract

Imaging of a 53-year-old Japanese man revealed two tumors in the liver and a tumor in the head of the pancreas with a swelling lymph node. A needle biopsy for the liver tumors was performed, revealing a neuroendocrine tumor. Enucleation, lymphadenectomy, and partial hepatectomy were performed. The microscopic examination identified many tumor cells with intracytoplasmic inclusions arranged in a nested, cord, or tubular fashion. The intracytoplasmic inclusions displayed densely eosinophilic globules and displaced the nuclei toward the periphery, which constitutes "rhabdoid" features. The tumor cells were positive for synaptophysin and weakly positive for NCAM, but negative for chromogranin A. Epithelial markers (AE1/AE3 and CAM5.2) accentuated intracytoplasmic globules. Pancreatic neuroendocrine tumors with rhabdoid features are very rare. Generally, rhabdoid features are aggressive and dedifferentiated characteristics of various types of tumor. Pancreatic neuroendocrine tumors containing rhabdoid cells tend to display extrapancreatic spread at the time of presentation, although some of these tumors with rhabdoid features are not always associated with aggressive behavior.

https://ift.tt/2v0oTC2

How to standardize the evaluation of tumor regression grading of gastrointestinal cancers after neoadjuvant therapy?

https://ift.tt/2M2nZeE

Cytogenetic and immunohistochemical study of 42 pigmented microcystic chromophobe renal cell carcinoma (PMChRCC)

Abstract

Pigmented microcystic chromophobe renal cell carcinoma (PMChRCC) is a recently described morphologic variant of ChRCC. We have identified 42 cases in 40 patients in the last 24 years. We have investigated their clinical, morphologic, immunohistochemical, and cytogenetic features. Chromosomal abnormalities of chromosomes 7 and 17 were evaluated by automated dual-color silver-enhanced in situ hybridization on paraffin-embedded tissue. Chromosomal imbalance was defined on the basis of changes in both chromosomal index and signal distribution. The main age was 60.20 years, being 34 males and 6 women. The mean tumor diameter was 4.84 cm, with 39 intrarenal tumors. Grossly, the tumors were solid with a brown dark colored. Microscopically, tumors consisted of pale and eosinophilic cells arranged in microcysts or microalveolar in a cribriform pattern; there were microcalcifications and a dark brown pigment, mostly extracellular. One case showed sarcomatoid transformation. All tumors were positive for epithelial membrane antigen (EMA), Claudin 7, and E-cadherin. Monosomy of 7 and 17 chromosomes was present in 1/36 cases and 2/37 cases, respectively. Polysomy of chromosome 7 and 17 was found in 26/36 cases and in 4/37, respectively. With a median follow-up of 74.05 months, 37 patients were alive without disease and two were alive with disease progression. PMChRCCs expand the morphologic spectrum of the ChRCC with an unusual immunohistochemical profile. Cytogenetically, they showed monosomy to chromosome (CHR) 17 as other ChRCCs and polysomy of CHR 7 infrequent to ChRCCs. We present the probably largest series of PMCRCC, confirming their low aggressive behavior, with exceptional sarcomatoid transformation and distant metastases.

https://ift.tt/2v1BUvg

Comparative clinicopathological and cytomorphological analyses of peritoneal carcinomatosis associated with metastatic breast carcinoma and primary peritoneal/ovarian carcinoma in patients with a history of breast carcinoma

Abstract

Causes of peritoneal carcinomatosis (PC) in patients with a history of breast carcinoma include both metastatic breast carcinoma (MBC) and primary peritoneal/ovarian carcinoma (PPOC). The origin of PC is important to determine the appropriate treatment strategy. Cytological examination of the peritoneal fluid (PF), which may be the first diagnostic approach to PC, is of distinct value in confirming the presence of malignant cells and determining the origin of PC. We analyzed the clinicopathological and cytomorphological characteristics of 33 patients with a history of breast carcinoma whose PF cytology contained malignant cells. Cases showing positive immunoreactivity for PAX8 and a lack of GATA3 expression were considered as PPOC. Sixteen patients developed PC caused by PPOC. PPOC patients were characterized by early-stage primary breast carcinoma, absence of non-peritoneal MBC before PC, and normal serum levels of CEA and CA15-3. Fourteen PPOC patients had pathogenic germline BRCA mutations. Cytological examination revealed that most of the PPOC cases had a dominant papillary arrangement of the tumor cells with severe nuclear pleomorphism, occasional bizarre nuclei, and atypical mitotic figures. Patients with PPOC who underwent cytoreductive surgery had a significantly longer survival time compared to those who did not, or MBC patients. In patients with a history of breast carcinoma presenting with PC, the presence of early-stage primary breast carcinoma, no prior non-peritoneal MBC, and a dominant papillary cellular arrangement pattern in the PF cytology were independent predictors of PPOC. Cytoreductive surgery significantly improved survival for patients with PPOC.

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Acute liver failure secondary to ABVD use

Hodgkin's lymphoma (HL) is a type of cancer originating in the lymph nodes. The preferred therapy for advanced HL is a combination of chemotherapies including doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD). ABVD has been standard therapy for advanced HL. It is generally considered as safe and rarely has been reported to cause acute liver failure. We present a case of 79-year-old woman with HL, who developed acute liver failure secondary to first cycle of ABVD chemotherapy.

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Recurrent invasive group A streptococcal infection with four-limb amputation in an immunocompetent child

We report a previously well paediatric patient with two distinct presentations of invasive group A streptococcus (GAS) infection resulting in significant morbidity. The first episode, following GAS pharyngitis, involved multiorgan dysfunction syndrome. This included cardiorespiratory and acute hepatorenal failure and purpura fulminans that eventually necessitated four-limb amputation. The second episode occurred 12 months later, from undetermined aetiology, and resulted in septic shock. Molecular analysis of the emm gene and PCR for Serum Opacity Factor revealed that the initial isolate was M Type 4 and sof gene positive while the second isolate was M Type 1 and sof gene negative. Immunological investigations, including CH50, quantitative IgA, IgM and IgG, and flow cytometry measuring lymphocyte subsets, and vaccine response to measles, mumps, rubella and pneumococcus were normal. This is the first report of recurrent bacteraemia from different strains of Streptococcus pyogenes infection in an apparently immunocompetent child.

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Primary renal angiosarcoma

An older male patient with a history of tachycardia treated with atenolol presented to an outside hospital on 22 February 2017 with acute right flank pain. He had a CT scan which revealed a large right renal mass with acute haemorrhage. He was initially managed with interventional radiology guided embolism on 25 February 2017 due to the ongoing bleeding and haemodynamic instability. He was then transferred to our institution. He underwent right radical nephrectomy on 13 March 2017. His pathology revealed a 12.5x6x4.5 cm mass consistent with angiosarcoma of the right kidney with negative margins. Final pathology was pT2b with extension of the mass into the renal vein and perirenal adipose tissue. He was discharged soon after surgery. He was recommended to undergo adjuvant chemotherapy.

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Extensive Mongolian spots and normocephaly: an uncommon presentation of infantile Sandhoffs disease

Description 

A 10-month-old male infant was brought to us with developmental stagnation since 5 months of age. He attained age-appropriate developmental milestones until 5 months of age, however over the next 2 months, he did not gain any new milestones followed by subsequent developmental regression in the form of loss of neck holding ability, social smile, mother regard, visual fixation and cooing. He was a first born to non-consanguineous parents, at term by caesarean delivery (due to non-progression of labour). The antenatal and perinatal periods were normal. There was no history of seizures, exaggerated startle response and extrapyramidal symptoms. The family history was unremarkable. On examination, he had normal head size (46.2 cm, 50th centiles), dysmorphic facial features (flat nasal bridge, hypertelorism, thick upper lip and upturned nose), bilateral cherry-red spots, extensive Mongolian spots (figure 1) and hepatomegaly. He also had generalised hypotonia, hyperactive muscle stretch reflexes and bilateral...

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Platypnoea-orthodeoxia syndrome exacerbated by kyphosis progression

This is a case of an 86-year-old woman with gradually progressive dyspnoea and hypoxaemia that occurred after a cardiac surgery. It was underdiagnosed for several years, but diagnosis was triggered by the finding of hypoxaemia even during supplemental oxygen administration when in the upright position, such as when taking a shower, that rapidly improved when the patient returned to the supine position. A thorough workup disclosed platypnoea–orthodeoxia syndrome (POS) associated with right-to-left shunting through a patent foramen ovale (PFO). Percutaneous closure of the PFO was performed. After treatment, the patient's arterial oxygen saturation gradually recovered to 98% on room air while she was in the sitting position and her symptoms disappeared. Reviewing this case retrospectively, we determined that the deviation of the spine with kyphosis progression had apparently proceeded as POS worsened over time. We therefore hypothesised that kyphosis progression had played a major role in the POS progression.

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Liver failure associated with mahogany seed extract consumption

A 45-year-old woman presented to the emergency department with jaundice of 2 weeks' duration. This was associated with mahogany seed extract (Skyfruit supplement) consumption for 6 months prior to admission. Examination was normal apart from scleral icterus and grade 2 encephalopathy. Liver function tests showed a hepatocellular pattern of derangement: alanine transaminase, 1267 U/L (10–36); aspartatetransaminase, 1255 U/L (10–30); alkaline phosphatase, 124 U/L (22–104); bilirubin, 258 µmol/L (3–21) with a prolonged prothrombin time of 16.8 s (9.2–11.0). Viral hepatitis work-up was largely unremarkable and liver biopsy showed moderate inflammatory infiltrates (mostly lymphocytic with scattered eosinophils) in the periportal region and lobule with bridging necrosis, favouring drug-induced liver injury. Withdrawal of the drug resulted in normalisation of liver function.

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Posterior shoulder dislocation: its worth another look

A 40-year-old woman presented to the emergency department with a painful left shoulder following a fall from a mountain bike. A radiograph of the clavicle and shoulder was carried out. A diagnosis of fractured left clavicle was made, which was treated conservatively in a sling. On day 3, she was reviewed in the fracture clinic and was found to still be in pain with reduced movement of the shoulder joint. A repeat radiograph of the shoulder joint showed a posterior dislocation. This required a closed reduction under general anaesthesia.

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Unusual case of bilateral haemotympanum after endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA)

We present a case of bilateral haemotympanum (HT) during endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA). A 64 year-old-man underwent EBUS-TBNA for mediastinal lymph nodes (LN) staging. Medical history included emphysema and angina. Medication included aspirin until the day before procedure. Full blood count and clotting screen were normal. He received sedation (5 mg midazolam, 1000 mcg alfentanil) and topical anaesthesia (16 mL 1% lignocaine) but coughed excessively throughout the procedure. Left hilar LN was the only area sampled. Spontaneous bleeding ensued from both ears towards the end of the procedure. Patient remained haemodynamically stable. The procedure was aborted and otolaryngology consult sought. Otoscopy showed bilateral haematoma from anterior ear canal with normal tympanic membranes and no hearing loss. Nasendoscopy revealed erythematous ostium of both Eustachian tubes. Bleeding stopped spontaneously and patient required no further imaging or treatment. We report this case to increase awareness of this very rare complication resulting from excessive coughing during EBUS-TBNA.

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MYH9-related disorders: a rare cause of neonatal thrombocytopaenia

Myosin heavy chain 9-related disorders (MYH9RD) are a genetic condition characterised by large platelets and thrombocytopaenia. The May-Hegglin anomaly (MHA), an uncommon condition with a potential risk of bleeding complications once thought to be separate, is now known to be part of MYH9RD.

There are very limited data on the clinical course and neonatal/paediatric outcome in children with MHA. We present the case of a newborn with a normal physical examination whose mother had MHA. Peripheral blood examination revealed a platelet count of 16x10⁹/L with giant platelets and neutrophils containing Döhle bodies. Neonatal brain ultrasound examination showed no haemorrhage. The infant received three platelet transfusions during the first 29 days of life, remaining asymptomatic. The genetic molecular test was positive for MYH9RD. It is important to identify at-risk infants with this condition and to initiate therapy to prevent related complications, if needed, in a multidisciplinary team approach.

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Fatal case of macrophage activation syndrome (MAS) in a patient with dermatomyositis and cytomegalovirus (CMV) viraemia

We describe a case of an adult with dermatomyositis (DM) who presents with a rash, high fevers, tachycardia and hypotension, initially concerning for an infectious aetiology or a DM flare. She was found to have cytomegalovirus viraemia which improved after starting valganciclovir. After extensive workup and lack of improvement with broad-spectrum antimicrobial therapy, intravenous immunoglobulin and steroids, the patient was diagnosed with macrophage activation syndrome after bone marrow biopsy and levels of soluble CD25 (soluble interleukin (IL)-2 receptor) and IL2 were obtained. Unfortunately, despite therapy with dexamethasone, anakinra and etoposide, the patient decompensated and the patient's family opted for comfort care. The patient subsequently expired in the intensive care unit.

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Florid hyperandrogenism due to a benign adrenocortical adenoma

A 26-year-old woman with a history of polycystic ovarian syndrome presented with secondary amenorrhea, worsening hirsutism, acne, deepening of voice and unexplained 10–20 kg weight gain. Her Ferriman-Gallway hirsutism score was 12 with cystic facial acne and increased masculine phenotype. Urine Beta-Human Chorionic Gonadotropins (bHCG) was negative. She had elevated serum testosterone of 551 ng/dL, androstenedione at 7.46 ng/mL and dehydroepiandrosterone sulfate (DHEAS) at 4243 µg/L. Overnight dexamethasone suppression test showed mildly unsuppressed cortisol (2.89 µg/dL). Urinary free cortisol along with paired serum cortisol and adrenocorticotrophic hormone (ACTH) tests were normal (55.4 µg/24 hours, 13.44 mcg/dL, 30.4 pg/mL respectively). Her leutinizing hormone (LH) was low(<0.1 mIU/mL), follicle stimulating hormone (FSH) low/normal (1.41 mIU/mL) with sex hormone binding globulin (SHBG) level 45nmol/L and the rest of the pituitary and adrenal workup was unremarkable. Thyroid stimulating hormone (TSH) was 2.15mU/mL. MRI revealed a 3.1 cm, indeterminate but well-defined left adrenal lesion and polycystic ovaries without abdominal lymphadenopathy. Given radiological appearances and despite biochemical concerns for adrenocortical malignancy, a multidisciplinary team meeting decision was made to proceed with laparoscopic adrenalectomy. Histology was consistent with a benign adenoma. Postoperatively, there was clinical and biochemical resolution of the disease.

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Unusual case of a small bowel leiomyoma presenting as an adnexal mass

This case report will discuss an interesting case of a premenopausal woman who presented with an adnexal mass consistent with a leiomyoma on imaging. However, intraoperatively, the mass was thought to be a gastrointestinal stromal tumour but histological diagnosis subsequently confirmed a leiomyoma arising from the small bowel.

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Acute liver failure and hepatic encephalopathy in exertional heat stroke

A 31-year-old man was brought to Accident & Emergency after collapsing during a race. On presentation, the patient had a temperature of 41.7°C (rectal). External cooling was started immediately. The patient was intubated in view of a Glasgow Coma Scale of 7 and was transferred to theintensive therapy unit. Laboratory results revealed an acute kidney injury, rhabdomyolysis, disseminated intravascular coagulopathy and acute liver failure. The patient was encephalopathic, jaundiced and difficult to sedate. His liver function continued to deteriorate with alanine aminotransferase (ALT) levels reaching 9207 U/L. King's Hospital Liver Centre, London was contacted for a possible liver transplant, and they advised an infusion of N-acetylcysteine. The following day liver function tests improved; thus, transplantation was not performed. The patient failed multiple sedation holds and required a tracheostomy. He continued to spike a fever. Despite no source of sepsis being found, the patient remained on broad spectrum antibiotics to cover for any potential infective causes until day 27. After 15 days, the patient's encephalopathy gradually improved. He was weaned off the ventilator and underwent intense physiotherapy. The patient was discharged from hospital one month after admission.

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