HMGB1 Binding to the RAGE Receptor Contributes to the Pathogenesis of Asthma

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


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HMGB1 Binding to the RAGE Receptor Contributes to the Pathogenesis of Asthma

Pediatric Allergy, Immunology, and Pulmonology, Ahead of Print.


https://ift.tt/2PH0ZEr

Carnitine palmitoyltransferase type 2 deficiency: novel mutation in a Native South American family with whole-body muscle magnetic resonance imaging findings: two case reports

The myopathic form of carnitine palmitoyltransferase type II deficiency is an inherited autosomal recessive metabolic myopathy usually starting in childhood. Most reports have been on European and Japanese pop...

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Early‐onset neutropenia after rituximab therapy for bullous pemphigoid

Clinical and Experimental Dermatology, EarlyView.


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Scarring alopecia with follicular papules in a father and his daughter

Clinical and Experimental Dermatology, EarlyView.


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In vitro activity of PBTZ169 against multiple Mycobacterium species [Mechanisms of Resistance]

In this study, we demonstrate that PBTZ169 exhibits significant differences in in vitro activity against multiple Mycobacterium species. The amino acid polymorphism at codon 387 of DprE1 can be used as a surrogate marker for in vitro susceptibility to PBTZ169 in mycobacteria. In addition, the amino acid substitution at codon 154 in DprE1 may be associated with acquired resistance to PBTZ169 in the M. fortuitum mutants.

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ATTRIBUTABLE COST AND LENGTH OF STAY OF NOSOCOMIAL GRAM-NEGATIVE BACTERIA CULTURES [Epidemiology and Surveillance]

Introduction: Few studies have estimated the excess inpatient cost due to nosocomial Gram-negative bacteria (GNB) cultures and those that do are often subject to time-dependent bias. Our objective was to generate estimates of the attributable cost of the underlying infections associated with nosocomial cultures using a unique inpatient cost dataset from the US Department of Veterans Affairs that allowed us to reduce time-dependent bias.

Methods: Our study included data from inpatient admissions between 10/1/2007 and 11/30/2010. Nosocomial GNB positive cultures were defined as positive clinical cultures for Acinetobacter, Pseudomonas, or Enterobacteriaceae from 48 hours after admission to discharge. Positive cultures were further classified by site and their level of resistance. We conducted analyses using both a conventional approaches and an approach aimed at reducing the impact of time-dependent bias. In both instances, we used multivariable generalized linear models to compare the inpatient costs and LOS between patients with and without a nosocomial Gram-negative bacteria cultures.

Results: Of the 404,652 patients included in the conventional analysis, 12,356 had a nosocomial GNB positive culture. The excess cost of nosocomial GNB positive cultures was significant regardless of specific pathogen, site, or resistance level. Estimates generated using the conventional analysis approach were 32.0% - 131.2% higher in magnitude than those generated using an approach to reduce time-dependent bias.

Conclusion: These results are important because they underscore the high financial burden attributable to these infections and provide a baseline that can be used to assess the impact of improvements in infection control.

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Genomic analysis of multi-resistant Staphylococcus capitis associated with neonatal sepsis [Epidemiology and Surveillance]

Coagulase-negative staphylococci (CoNS) such as Staphylococcus capitis, are major causes of bloodstream infections in neonatal intensive care units (NICUs). Recently a distinct clone of S. capitis (designated S. capitis NRCS-A) has emerged as an important pathogen in NICUs internationally. Here, 122 S. capitis isolates from New Zealand (NZ) underwent whole genome sequencing (WGS), and these data were supplemented with publicly available S. capitis sequence reads. Phylogenetic and comparative genomic analyses were performed, as were phenotypic assessments of antimicrobial resistance, biofilm formation and plasmid segregational stability on representative isolates. A distinct lineage of S. capitis was identified in NZ, associated with neonates and the NICU environment. Isolates from this lineage produced increased levels of biofilm, displayed higher levels of tolerance to chlorhexidine, and were multidrug-resistant. Although similar to globally circulating NICU-associated S. capitis at a core genome level, NZ NICU S. capitis isolates carried a novel, stably maintained multidrug-resistant plasmid that was not present in non-NICU isolates. Neonatal blood culture isolates were indistinguishable to environmental S. capitis isolates found on fomites such as stethoscopes and neonatal incubators, but were generally distinct from those isolates carried by NICU staff. This work implicates the NICU environment as a potential reservoir for neonatal sepsis caused by S. capitis, and highlights the capacity of genomics-based tracking and surveillance to inform future hospital infection control practices aimed at containing the spread of this important neonatal pathogen.

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Alanine scanning mutagenesis of the MEDI4839 (Suvratoxumab) epitope reduces alpha toxin lytic activity in vitro and S. aureus fitness in infection models [Clinical Therapeutics]

Alpha toxin (AT) is a cytolytic pore-forming toxin that plays a key role in Staphylococcus aureus pathogenesis, consequently extensive research was undertaken to understand the AT mechanism of action and its utility as a target for novel prophylaxis and treatment strategies against S. aureus infections. MEDI4893 (Suvratoxumab) is a human anti-AT IgG1 monoclonal antibody (mAb), which targets AT and is currently in Phase 2 clinical development. As shown previously, the MEDI4893-binding epitope on AT is comprised of the highly conserved amino acid regions 177-200 and 261-271, suggesting these amino acids are important for AT function. To test this hypothesis, and gain insight into the effect mutations in the epitope on AT neutralization by MEDI4893, nine MEDI4893 contact residues in AT were individually mutated to alanine. Consistent with our hypothesis, 8 out of 9 mutants exhibited >2-fold loss in lytic activity resulting from a defect in cell binding and pore formation. MEDI4893 binding affinity was reduced >2-fold (2 – 27-fold) for 7 out of 9 mutants and no binding detected for W187A mutant. MEDI4893 effectively neutralized all the lytic mutants in vitro and in vivo. When the defective mutants were introduced into a S. aureus clinical isolate, the mutant-expressing strains exhibited less severe disease in mouse models and were effectively neutralized by MEDI4893. These results indicate the MEDI4893 epitope is highly conserved due, in part to its role in AT pore-formation and bacterial fitness, thus decreasing the likelihood for the emergence of mAb-resistant variants.

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Argentilactone Molecular Targets in Paracoccidioides brasiliensis Identified by Chemoproteomics [Mechanisms of Action]

Paracoccidioidomycosis (PCM) is the cause of many deaths from systemic mycoses. The etiological agents of PCM belong to the Paracoccidioides genus, which is restricted to Latin America. The infection is acquired through the inhalation of conidia that primarily lodge in the lungs and may disseminate to other organs and tissues. The treatment for PCM is commonly performed via the administration of antifungals such as amphotericin B, co-trimoxazole, and itraconazole. The antifungal toxicity and side effects, in addition to their long treatment times, have stimulated research for new bioactive compounds. Argentilactone is compound that was isolated from the Brazilian savanna plant Hyptis ovalifolia, and it has been suggested to be a potent antifungal, inhibiting the dimorphism of P. brasiliensis and the enzymatic activity of isocitrate lyase, a key enzyme of the glyoxylate cycle. This work was developed due to the importance of elucidating the putative mode of action of argentilactone. The chemoproteomics approach via affinity chromatography was the methodology used to explore the interactions between P. brasiliensis proteins and argentilactone. A total of 109 proteins were identified and classified functionally. The most representative functional categories were related to amino acid metabolism, energy, and detoxification. Argentilactone inhibited the enzymatic activity of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase. Furthermore, argentilactone induces the production of reactive oxygen species and inhibits the biosynthesis of cell wall polymers.

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Reliable and easy-to-use Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) assay for quantification of Olorofim (F901318) - a novel antifungal drug - in human plasma and serum [Analytical Procedures]

Background A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, Olorofim (formerly F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated.

Methods Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope labeled analogue of F901318 was employed as internal standard. Chromatographic separation was achieved using a 50 mm x 2.1 mm, 1.9μm, polar Hypersil Gold C18 column and isocratic mobile phase consisting of 0.1 % formic acid/acetonitrile (60%/40%, v/v) at a flow rate of 330 μl/min. The analyte was detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode with positive heated electrospray ionization (HESI⁺) within a single runtime of t = 2.00 min.

Results The present LC-MS/MS-method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the US Food and Drug Administration (FDA). Linearity of F901318 concentration ranges was verified by the Mandel-test. Calibration curve was tested linear across the range and fitted using least squares regression with a weighting factor of the reciprocal concentration. Limit of detection was: LOD = 0.0011 mg/l, lower limit of quantitation was: LLOQ = 0.0033 mg/l. Intra-day and inter-day precisions ranged from 1.17% to 3.23% for F901318, and intra-day and inter-day accuracies (%bias) ranged from 0.75% to 5.01%.

Conclusion The method was established for the rapid quantitation of F901318 concentrations in serum and plasma samples in patient trials, and optimizes TDM in applying an easy-to-use single method.

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Diversity of high-level aminoglycoside resistance mechanisms among Gram-negative nosocomial pathogens in Brazil [Letters]

Studies on high-level aminoglycoside resistance (HLAR), especially pertaining to 16S ribosomal RNA methyltransferases (16S-RMTases), have mostly involved Enterobacteriales, whereas comparable data on glucose-non-fermenting Gram-negative bacilli (NFGNB) remain scarce (1, 2)....

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Implementation of Rapid Diagnostic Testing without Active Stewardship Team Notification for Gram-Positive Blood Cultures in a Community Teaching Hospital [Clinical Therapeutics]

In community hospitals, antimicrobial stewardship team notification of rapid diagnostic testing (RDT) results may not be feasible. A retrospective, quasi-experimental study was conducted evaluating 252 adult inpatients with blood cultures positive for Gram-positive cocci in clusters (pre-RDT n=143, post-RDT n=109). Median time to appropriate therapy was significantly shorter in the post-RDT group (15 vs. 0 hr, p <0.001), and mean length of stay for patients with Coagulase-negative staphylococcus was significantly shorter (10.5 vs. 7.7 days, p=0.015).

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Antimicrobial Prophylaxis for Patients Undergoing Cardiac Surgery: Intraoperative Cefazolin Concentrations and Sternal Wound Infections [Pharmacology]

This study characterizes the pharmacodynamics of antimicrobial prophylaxis and sternal wound infections following cardiac surgery. Duration of surgery and cefazolin plasma concentration during wound closure were independently associated with surgical site infection at 30 days. Furthermore, duration of surgery >346 minutes and total cefazolin closure concentration <104 mg/L were significant thresholds for an increased risk of infection. This study provides new data that informs dosing strategies for effective AP in patients undergoing cardiac surgery with cardiopulmonary bypass.

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Impact of efavirenz, ritonavir-boosted lopinavir and nevirapine based antiretroviral regimens on the pharmacokinetics of lumefantrine and safety of artemether-lumefantrine in falciparum-negative HIV-infected Malawian adults stabilized on antiretroviral therapy [Clinical Therapeutics]

There is conflicting evidence of the impact of commonly used antiretroviral therapies (ARTs) on the pharmacokinetics of lumefantrine and safety profile of artemether-lumefantrine. We compared the area under the concentration-time curve (AUC_{0-14 days}) of lumefantrine and safety profile of artemether-lumefantrine in malaria-negative human immunodeficiency virus (HIV) infected adults in two steps. In step 1, a half-dose adult course of artemether-lumefantrine was administered as a safety check in four groups (n=6/group): (i) antiretroviral-naïve, (ii) on nevirapine-based ART, (iii) on efavirenz-based ART and (iv) on ritonavir-boosted lopinavir-based ART. In step 2, a standard-dose adult course of artemether-lumefantrine was administered to a different cohort in three groups (n=10-15/group): (i) antiretroviral-naïve, (ii) on efavirenz-based ART and (iii) on ritonavir-boosted lopinavir-based ART. In step 1, lumefantrine's AUC_{0-14 days} was 53% [95% CI: 0.27-0.82] lower in the efavirenz-based ART group than the ART-naïve group and was 2.4 [95% CI: 1.58-3.62] and 2.9 [95% CI: 1.75-4.72] times higher in the nevirapine and ritonavir-boosted lopinavir groups, respectively. In step 2, lumefantrine's AUC_{0-14 days} was 1.9 [95% CI: 1.26-3.00] times higher in the ritonavir-boosted lopinavir group and not significantly different between the efavirenz- and ART-naïve groups (0.99 [95% CI: 0.63-1.57]). Frequent cases of haematological abnormalities (thrombocytopenia and neutropenia) were observed in the nevirapine group in step 1, leading to a recommendation from the data and safety monitoring board not to include a nevirapine group in step 2. Artemether-lumefantrine was well tolerated in the other groups. The therapeutic implications of these findings need to be evaluated among HIV-malaria co-infected adults.

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Investigating the efficacy of triple artemisinin-based combination therapies (TACTs) for treating Plasmodium falciparum malaria patients using mathematical modelling [Analytical Procedures]

The first line treatment for uncomplicated falciparum malaria is artemisinin-based combination therapy (ACT), which consists of an artemisinin derivative co-administered with a longer acting partner drug. However, the spread of Plasmodium falciparum resistant to both artemisinin and its partner drugs poses a major global threat to malaria control activities. Novel strategies are needed to retard and reverse the spread of these resistant parasites. One such strategy is triple artemisinin-based combination therapy (TACT). We developed a mechanistic within-host mathematical model to investigate the efficacy of a TACT (dihydroartemisinin-piperaquine-mefloquine - DHA-PPQ-MQ), for use in South-East Asia, where DHA and PPQ resistance are now increasingly prevalent. Comprehensive model simulations were used to explore the degree to which the underlying resistance influences the parasitological outcomes. The effect of MQ dosing on the efficacy of TACT was quantified at varying degrees of DHA and PPQ resistance. To incorporate interactions between drugs, a novel model is presented for the combined effect of DHA-PPQ-MQ, which illustrates how the interactions can influence treatment efficacy. When combined with a standard regimen of DHA and PPQ, the administration of three 6.7 mg/kg doses of MQ was sufficient to achieve parasitological efficacy greater than that currently recommended by WHO guidelines. As a result, three 8.3 mg/kg doses of MQ, the current WHO recommended dosing regimen of MQ, combined with DHA-PPQ, has potential to produce high cure rates in the regions where resistance to DHA-PPQ has emerged.

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Adjunctive Clavulanic Acid Abolishes the Cefazolin Inoculum Effect in an Experimental Rat Model of Methicillin-Sensitive Staphylococcus aureus Endocarditis [Experimental Therapeutics]

We tested the ability of clavulanic acid to restore the efficacy of cefazolin against S. aureus TX0117, which exhibits the cefazolin inoculum effect (CzIE). In the rat infective endocarditis model, the co-administration of cefazolin plus clavulanic acid resulted in a significant reduction of bacterial counts (7.1 ± 0.5 log₁₀ CFU/g) compared to cefazolin alone (2 ± 0.6 log₁₀ CFU/g; p<0.0001). The addition of a β-lactamase inhibitor may be a viable strategy for overcoming the CzIE.

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The Colistin Resistance Gene, mcr-1, is Prevalent in Commensal E. coli Isolated from Lebanese Pre-harvest Poultry [Letters]

Antimicrobial resistance is a serious global problem....

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Single-day doxycycline therapy for Mediterranean spotted fever: a prospective cohort study [Clinical Therapeutics]

The objective of this study is to evaluate the results of single-day doxycycline therapy for Mediterranean spotted fever (MSF). This is a prospective cohort study of cases with confirmed MSF treated with the single-day doxycycline regimen in a teaching hospital from 1990 to 2015. Patients received two oral doses of 200 mg of doxycycline for one day. The outcomes evaluated were time interval between start of treatment and apyrexia, time interval between start of treatment and disappearance of other symptoms, adverse reactions to treatment and death. The study included 158 subjects, 18 of whom (11.4%) had a severe form of MSF and 31 (19.6%) were >65 years. The interval between onset of symptoms and start of treatment was 4.31±1.54 days. All patients recovered uneventfully. Fever disappeared 2.55±1.14 days after the start of treatment. The remaining symptoms (headache, arthromyalgia) disappeared 3.63±1.35 days after the start of treatment. Only one patient had a delay in reaching apyrexia (8 days). The fever disappeared somewhat later in severe cases (median, 3 [interquartile range {IQR}, 2-4] days) than in non-severe cases (median, 2 [IQR, 2-3] days). Likewise, the remaining symptoms disappeared later in severe cases (median, 5 [IQR, 4-6] days) than in non-severe cases (median, 3 [IQR, 3-4] days). The outcome was similar in the elderly and in the non-elderly patients. Eight patients had mild adverse effects possibly related to treatment. The results of the study confirm that single-day doxycycline therapy is an effective and well-tolerated treatment for MSF, including elderly patients and severe cases.

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Simplified aztreonam dosing in patients with end stage renal disease: results of a Monte Carlo simulation [Clinical Therapeutics]

The manufacturer-labeled aztreonam dosing in patients with a creatinine clearance of <10 mL/min/1.73m² is complex. It is unknown if simpler post-hemodialysis dosing administered once daily or thrice weekly can reliably achieve pharmacodynamic goals. We found that 1 or 2 grams once daily post-hemodialysis had a >90% probability of target attainment up to an MIC of 4 or 8mg/L, respectively. Thrice weekly dosing should generally be avoided except in non-severe infections where the MIC is ≤0.5mg/L.

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In Vitro Antiviral Profile of Ruzasvir: A Potent and Pan-genotype Inhibitor of HCV NS5A [Antiviral Agents]

Inhibition of NS5A has emerged as an attractive strategy to intervene in HCV replication. Ruzasvir (formerly MK-8408) was developed as a novel NS5A inhibitor to improve upon the potency and barrier to resistance of early compounds. Ruzasvir inhibited HCV RNA replication with EC₅₀ values of 1-4 pM in Huh 7 or 7.5 cells bearing replicons for HCV genotypes 1-7. The antiviral activity was modestly (10-fold) reduced in the presence of 40% normal human serum. The picomolar potency in replicon cells extended to sequences of clinical isolates available in public databases that were synthesized and tested as replicons. In GT1a, ruzasvir inhibited common NS5A resistance-associated substitutions (RASs) with the exception of M28G. De novo resistance selection studies identified pathways with certain amino acid substitutions at residues 28, 30, 31 and 93 across genotypes. Substitutions at position 93 were more common in genotypes (GTs) 1-4 while changes at position 31 emerged frequently in GTs 5 and 6. With the exception of GT4, the reintroduction of selected RASs conferred a 100-fold or more potency reduction in the antiviral activity of ruzasvir. Common RASs from other classes of direct-acting antiviral agents (DAAs) did not confer cross-resistance to ruzasvir. The interaction of ruzasvir with NS3/4A protease inhibitor (grazoprevir) and NS5B polymerase (uprifosbuvir) pro-drug was additive to synergistic with no evidence of antagonism or cytotoxicity. The antiviral profile of ruzasvir supported its further evaluation in human trials in combination with grazoprevir and uprifosbuvir.

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The impacts of L1 promoter variation and L2 clavulanate susceptibility on ticarcillin-clavulanate susceptibility of Stenotrophomonas maltophilia [Mechanisms of Resistance]

Inducible expression of L1 and L2 β-lactamases is the principal mechanism responsible for β-lactam resistance in Stenotrophomonas maltophilia. Ticarcillin-clavulanate (TIM) is one of the few effective β-lactam for S. maltophilia treatment. Clavulanate (CA) is a β-lactamase inhibitor which specifically targets to Class A, C, and D β-lactamases. In view of the presence of class B L1 β-lactamase, it is of interest to elucidate why TIM is valid for S. maltophilia treatment. The L1, L2 allelic variation and TIM susceptibility from 22 clinical isolates were established. According to L1 and L2 protein sequences and TIM susceptibility, three L1-based phylogenetic clusters (L1-A, L1-B, and L1-C) and three L2-based phylogenetic clusters (L2-A, L2-B1, and L2-B2) were classified. The contribution of each L1- and L2-based phylogenetic cluster to ticarcillin (TIC) and TIM susceptibility was investigated. All L1s and L2s tested contributed to TIC resistance. L1s tested were inert to CA; nevertheless, the sensitivities of L2s toward CA were greatly different. In addition, the genetic organizations upstream of the L1 gene much varied in these isolates. At least three different L1 promoter structure (K279a-type, D457-type, and none) were found from the 22 isolates assayed. The difference in the L1 promoter structure made a great impact on the TIC-induced L1 β-lactamase activities. Collectively, the L1 promoter activity responding to TIC challenge and L2 susceptibility toward CA are critical factors determining TIM susceptibility in S. maltophilia.

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Therapeutic drug monitoring of voriconazole in children: experience from a tertiary care center in China [Clinical Therapeutics]

Voriconazole is a broad-spectrum triazole antifungal and the first line treatment for invasive aspergillosis (IA). The aim of this research was to study the dose adjustments of voriconazole as well as the affecting factors influencing voriconazole trough concentrations in Asian children to optimize its daily administration. Clinical data were analyzed of inpatients aged 2-14 years who were subjected to voriconazole trough concentrations monitoring from June 1, 2015 to December 1, 2017. A total of 138 voriconazole trough concentrations from 42 paediatric patients were included. Voriconazole trough concentrations at steady state ranged from 0.02 to 9.35mg/liter with high inter- and intra-individual variability. Only 50.0% of children achieved the target range (1.0~5.5 mg/liter) at initial dosing, while 35.7% of children were subtherapeutic, and 14.3% of children were supratherapeutic at initial dosing. There was no correlation between initial trough concentrations and initial dosing. A total of 28.6% of children (12/42) adjusted the dose according to trough concentrations. Children aged <6,6~12 and >12 years old required median oral maintenance dose to achieve the target range of 11.1, 7.2 and 5.3 mg/kg twice daily respectively (P=0.043). The average doses required to achieved the target range were 7.7 mg/kg and 5.6 mg/kg, respectively, and were lower than the recommended dosage (P=0.033, 0.003). Affecting factors such as administration routes and co-administration with proton pump inhibitors (PPIs) explained 55.3% of variability in voriconazole exposure. Therapeutic drug monitoring (TDM) of voriconazole could help to individualize antifungal therapy for children and provide guidelines for TDM and dosing optimization in Asian children.

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Immunosuppressed Adult Zebrafish Model of Mucormycosis [Letters]

Mucormycosis is a life threatening, rapidly progressing infection associated with high mortality....

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Randomized, Double-Blind, Placebo-Controlled Studies of the Safety and Pharmacokinetics of Single and Multiple Ascending Doses of Eravacycline [Pharmacology]

Eravacycline is a novel, fully-synthetic fluorocycline antibiotic with in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative pathogens including multi-drug resistant (MDR) bacteria. The pharmacokinetics (PK), urinary excretion, and safety/tolerability of intravenous (IV) eravacycline were evaluated in single- and multiple ascending dose studies. Healthy subjects received single IV doses of 0.1 to 3 mg/kg or 10 days treatment with 0.5 or 1.5 mg/kg q24h over 30 minutes, 1.5 mg/kg q24h over 60 minutes, or 1 mg/kg q12h over 60 minutes. After single doses, total exposure (AUC) and peak plasma concentrations (C_max) of eravacycline increased in an approximately dose-proportional manner. After multiple doses, steady-state was achieved within 5 to 7 days. Accumulation (AUC_0-24) ranged between approximately 7% and 38% with the q24h dosing regimens and 45% with 1 mg/kg q12h. Eravacycline was generally well tolerated, with dose-related nausea, infusion site effects, and superficial phlebitis that were mild or moderate. These results provide support for the 1 mg/kg q12h regimen used in clinical studies of eravacycline.

https://ift.tt/2LuxSAJ

Statement from NCI Director Dr. Norman E. Sharpless on the Death of Senator John McCain

Senator John McCain, a long-time supporter of cancer research, passed away on August 25.

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FDA Clears First Tretinoin Lotion for Acne (Altreno)

Tretinoin 0.05% lotion provided the proven efficacy of tretinoin in a generally well-tolerated formulation; skin dryness, pain, swelling, irritation, and peeling were reported in 4% of patients or less in clinical trials.
FDA Approvals

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Memorial Hermann-Texas Medical Center Ranked Among the Top 20 Nationally in Adult ENT Care by US News & World Report

Memorial Hermann-Texas Medical Center's Otorhinolaryngology Service holds the 19th spot in the nation among hospitals that provide adult ENT care,...

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Toddler Enjoys Sound of Success

A new cochlear implant is helping 3-year-old Bellemere Hernandez hear for the first time. The toddler faces several disorders caused...

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UTHealth Sponsors 2018 ORL Frontiers

More than 70 physicians and other health care professionals attended 2018 ORL Frontiers, an annual CME event that highlights emerging...

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Congratulations to Our Graduating Residents

Uma Ramaswamy, MD, and Matthew A. Tyler, MD, have completed their residencies in otorhinolaryngology at McGovern Medical School at UTHealth. ...

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History of Eczema is Associated with More Severe Hospital Course in Children Hospitalized for Asthma

Asthma is a major cause of childhood morbidity in the United States. Poorly-controlled asthma results in recurrent emergency room visits, hospital admissions, and even death.1 Hospital admissions for asthma also incur significant cost to society.2 Identifying risk factors and comorbidities that contribute to severity of asthma during hospital admissions may improve asthma control and prevent further admissions. One recent study found that increased serum total IgE level is associated with patients admitted to the hospital for asthma, as compared to those being treated in an outpatient setting.

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Management of Bilateral Facial Palsy

Bilateral facial paralysis is a rare entity that occurs in both pediatric and adult patients and can have congenital or acquired causes. When paralysis does not resolve with conservative or medical management, surgical intervention may be indicated. This article presents the authors' preferred technique for facial reanimation in patients with bilateral congenital facial paralysis. Specifically, a staged bilateral segmental gracilis transfer to ipsilateral nerve to masseter is discussed.

https://ift.tt/2PI4wCj

“My clothes, pillowcases, and bedsheets have turned green-colored!”

Introduction: Chromhidrosis is a rare disorder in which there is pigmentation of sweat in a variety of colors. The condition can be categorized into apocrine, pseudoeccrine, and true eccrine chromhidrosis. Although it does not cause serious health problem, it may be associated with psychologic stress and social embarrassment. We report a rare case of idiopathic chromhidrosis in a healthy middle-aged female with no significant medical history. A 56-year-old woman with no significant medical history and no personal history of skin cancer presented with a chief complaint "my clothes, pillows, and bedsheets have turned green-colored from my sweats." The patient has noticed light green-colored stains on her pillow cases, bedsheets, and her underwear, shirts, and bras for the past 6 months without any identifiable precipitants or triggers.

https://ift.tt/2wADXGH

Clinical assessment of the local tolerance and cosmetic efficacy of a topical skin care formulation used after 70% glycolic acid facial skin rejuvenation procedures in healthy female subjects: A randomized, controlled, evaluator-blind study

Background: Facial chemical peels are among the most widespread nonsurgical cosmetic procedures. Post-peeling guidelines recommend only the general use of topical emollients and the need for high factor broad spectrum sunscreens. However, clinical evidence on the use of specific emollients in this indication is limited.

https://ift.tt/2PIPlIZ

Clinical complications of lepra reactions: An in-patient experience from Pakistan

Introduction: The World Health Organization stated the global prevalence of leprosy as 176,176 cases at the end of 2015. Leprosy is an incapacitating infectious disease primarily affecting the skin and peripheral nerves. Immunologic complications of leprosy occur as immune-mediated lepra reactions type 1 and 2. These reactions remain a diagnostic dilemma for many physicians, dermatologists and neurologists. Despite the success of multidrug therapy these reactions cause considerable morbidity and physical disabilities by nerve damage.

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Clinical evaluation of 11 investigational allergens in TRUE Test panel 3.2 in children and adolescents

Background: Epicutaneous patch testing is the criterion standard method to confirm contact sensitization, the first step in making the diagnosis of allergic contact dermatitis (ACD) in both adult and pediatric populations. Eleven new investigational allergens of the Thin-Layer Rapid Use Epicutaneous (TRUE) Test panels had been Food and Drug Administration (FDA) approved for adults for diagnosis of ACD, but not in children at the time of this study.

https://ift.tt/2PMUNLc

Clinical evaluation of a comprehensive topical antioxidant system in mildly to moderately photodamaged skin

Background: Topical antioxidants are fundamental to skin health. A product containing water-soluble, enzymatic, and lipid-soluble antioxidants provides protection at all cellular levels of the skin against the visible effects of ultraviolet (UV) and environmental damaging free-radicals.

https://ift.tt/2wAEqsr

Sensitive skin compatibility of cleansing wipes

Background: Individuals with sensitive skin should use skin cleansing products that are efficacious, nonirritating, and help maintain a healthy skin barrier. Facial cleansing wipes are a popular format used for general cleansing and make-up removal. A facial wipe was developed with nonionic surfactants, which were selected to provide nonirritating and efficacious cleansing, due to the surfactants' low protein-binding affinity. The unique blend of spun-lace nonwoven fibers in this facial wipe offers gentle and effective cleansing.

https://ift.tt/2PIswoL

The rates of herpes zoster, hepatitis c, and tuberculosis among patients with psoriasis treated with apremilast, biologics, conventional systemics, and corticosteroids in the U.S. MarketScan database

Background: Patients (pts) with psoriasis are at increased risk for infection. We compared rates of treated herpes zoster, hepatitis C (HepC), and tuberculosis (TB) by treatment in pts with psoriasis.

https://ift.tt/2wre0ZT

Point-of-care decision support for appropriate acne management

Background: Referral from primary care providers for acne is a costly process associated with high no-show rates and delayed treatment. We previously demonstrated that models of algorithm-based acne care may lead to reductions in the rate of dermatology referrals, missed appointments, and delayed treatment. In this retrospective chart analysis, we evaluate the impact of an electronic decision support tool on the management of patients referred for acne.

https://ift.tt/2PGvpXp

Superior even skin tone and antiaging benefit of combination of 4-hexyl resorcinol and niacinamide

Unevenness of skin tone is a pervasive problem that develops with aging and sun exposure. Skin color results from the action of multiple biologic pathways that primarily control melanin synthesis and distribution. In the present studies we explored the possibility of using a synergistic approach to enhance the efficacy of cosmetic products. We evaluated the in vitro and clinical efficacy of a combination of 4-hexyl resorcinol, a known tyrosinase inhibitor and niacinamide, a melanosome transfer inhibitor, both of which regulate two different process involved in the development of skin color.

https://ift.tt/2LvhQa1

Reasons for discontinuation of secukinumab between weeks 12 and 52 in psoriasis patients responsive to treatment at week 12

Background: Patients enrolled in RCTs are subject to strict study guidelines to ensure validity, thus limiting a patients' ability to manage their own treatment plan. As such, rates and reasons for treatment discontinuation reported in secukinumab RCTs may not correlate to outcomes seen in the real world. Therefore, we aimed to investigate reasons for discontinuation of secukinumab between weeks 12 and 52 in patients who achieved efficacious outcomes at week 12.

https://ift.tt/2PHxmTm

Noxious nocebos in dermatology

Importance: Negative expectations on the part of the patient or the dermatologist can negatively influence treatment responses resulting in the nocebo effect.

https://ift.tt/2LxeSl3

The burden of nail psoriasis: A real-world analysis from the Corrona Psoriasis Registry

Objective: Nail psoriasis (Pso) is often correlated with more severe psoriatic disease and is difficult to treat; only a few studies have shown its association with significant functional and psychosocial impairment. The objective of this study was to describe the impact of nail Pso on clinical and patient-reported outcomes (PROs) among patients enrolled in the Corrona Psoriasis Registry.

https://ift.tt/2PHBRNC

Sonidegib preplanned subgroup analyses of objective response rates: 30-month results from the BOLT study

Background: Sonidegib 200 mg once daily (qd) was approved in the United States for patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy based on results of the phase 2 BOLT study (NCT01327053). The 30-month overall efficacy and safety data from the BOLT study have been presented; here we report the 30-month results from a preplanned subgroup analysis for the primary end point, the objective response rate (ORR), in patients with laBCC receiving 200 mg, data which have not been presented.

https://ift.tt/2Lws89N

Staphylococcus aureus biofilm in atopic dermatitis (AD): In vitro model and in vivo early AD study

Introduction and objectives: Biofilm is one of the most important virulence factors in infectious diseases; biofilm-associated bacteria show an innate resistance to antibiotics and host innate immune defenses. The presence of S. aureus biofilms in AD lesions has been described recently. In AD, biofilm seems to play a role in pruritus, inflammation and in resistance to antimicrobial peptides (PAMs). We used in vitro models to study the role of S. aureus and its biofilm in AD and to evaluate a lipid-replenishing balm specifically formulated for baby and child with atopic skin.

https://ift.tt/2PMUDU6

Patient profile of nonresponders to ustekinumab in moderate-to-severe psoriasis patients enrolled in the Corrona Psoriasis Registry

Objective: Describe the baseline characteristics of moderate to severe psoriasis (Pso) patients enrolled in the Corrona Psoriasis Registry who respond/did not respond to ustekinumab.

https://ift.tt/2LvhpMV

The impact of dermatology lectures on internal medicine residents

Background: Most medical students receive an average of 10 hours of dermatology teaching before starting residency, and only 25% take dermatology elective in medical school. Internal medicine (IM) residents regularly encounter dermatologic complaints and diseases, yet 63% of primary care residents state that they are inadequately prepared to diagnose common skin disorders. A recent study showed that an isolated didactic curriculum is a sufficient teaching method for IM residents, as measured by a multiple-choice test.

https://ift.tt/2PHwONi

Targeted phototherapy: An eight-year experience in a tertiary dermatologic center

Background: Targeted phototherapy is the localized delivery of ultraviolet (UV) light to affected areas of skin. The commonest indications for targeted UV therapy include localized psoriasis, vitiligo, atopic dermatitis, and lymphoproliferative skin disorders involving a limited area of the body or difficult-to-treat anatomic areas. In view of advancing treatment options in the field of phototherapy for common skin conditions, little has been published about targeted phototherapy in Asian patients, especially in big numbers.

https://ift.tt/2Lvhgcl

Subcorneal pustular dermatosis (Sneddon-Wilkinson disease): A case report with good reponse to cyclosporine and dapsone treatment

Introduction: Subcorneal pustular dermatosis (SCPD), or Sneddon-Wilkinson disease, is a rare chronic-relapsing skin disorder that manifests as flaccid sterile pustules without systemic symptoms. It typically presents in women over the age of 40, affecting the trunk and intertriginous areas. The treatment of choice is dapsone, although other drugs have been used. We report a 65-year-old woman with SCPD with a good response to cyclosporine and dapsone treatment.

https://ift.tt/2PG8MCp

Skin cancer with history of actinic keratosis: A large, urban, single-center, midwestern U.S. population observational study

Introduction: Actinic keratosis (AK) may be considered by some to be an incipient form of squamous cell carcinoma (SCC) as the rate of SCC in individuals with AK has been estimated at 0.025%-16%. There is much less reported evidence for AK association with basal cell carcinoma (BCC) and melanoma (MM). The aim of this study is to determine if an association exists between AK and nonmelanoma skin cancer (NMSC; SCC and BCC) and between AK and MM in a large midwestern U.S. patient population.

https://ift.tt/2LxeR0t

Scrofuloderma: Beyond a cutaneus tuberculosis

Science: Tuberculosis (TB) is a major public health issue worldwide. It has various clinical presentations making the diagnosis a challenge. Skin involvement is uncommon and scrofuloderma is the most frequent type of cutaneous TB. It results from direct dissemination to the skin of an underlying structure, primarily lymph nodes, and in rare cases can occur as a manifestation of miliary TB. An adequate anamnesis along with clinical suspicion are fundamental for timely diagnosis and treatment.

https://ift.tt/2PI7Fly

Thrombocytopenia-associated multiple-organ failure (TAMOF): recognition and management

Thrombocytopenia-associated multiple-organ failure (TAMOF) is an increasingly fatal phenomenon that may be associated with sepsis. TAMOF results from immune dysregulation and impaired activity of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 motif, member 13. Early recognition of this premorbid condition and specific management results in a significantly improved outcome. Herein, we report the presentation and management of a 2-year-old child with TAMOF who was successfully treated with plasma exchange and recovered without long-term sequelae.

https://ift.tt/2wghoYo

Corneal epithelial toxicity with intravitreal methotrexate in a case of B-cell lymphoma with ocular involvement

A 49-year-old woman, known case of diffuse large B-cell lymphoma, presented with complaints of floater in both eyes since 3 days. On examination, visual acuity was 0.18 logMAR in both eyes. Indirect ophthalmoscopy revealed presence of vitreous clumps. Vitreous biopsy was done and the histopathological report suggested a diagnosis of ocular lymphoma. The patient was treated with weekly injections of intravitreal methotrexate in both eyes. The patient developed severe photophobia, watering, redness and diminution of vision in the both eyes 2 days following the fifth dose of intravitreal methotrexate. Severe limbitis with annular corneal epitheliopathy and corneal haze was noted on slit-lamp examination. The patient was started on topical lubricants, antibiotic, ciclosporin, loteprednol, folinic acid and oral folic acid. Complete resolution was noted at 2-week follow-up. The patient, however, refused further injections and was kept on close follow-up to look for recurrence of the disease.

https://ift.tt/2P6dOXE

Paraneoplastic cerebellar degeneration as a manifestation of metastatic recurrent carcinoma breast: rare scenario

Carcinoma breast presenting with paraneoplastic cerebellar degeneration is a rare scenario. We report a case of a 52-year-old woman, which is a follow-up case of completely treated carcinoma breast presenting with paraneoplastic cerebellar degeneration which, on investigation, revealed metastatic disease with recurrence at previous scar site and metastasis to contralateral axilla. The patient was given pulse methyl prednisolone therapy and underwent wide local excision of nodule and right axillary lymph node dissection with 14 cycles of trastuzumab and paclitaxel as adjuvant therapy. However, there was no detectable change in neurological symptoms at 6-month follow-up postoperatively. This case report highlights the need for clinicians to be aware of all possible presentations of carcinoma breast and its recurrence, including rare manifestations as in this case.

https://ift.tt/2wijeIh

'Stony shoulder: an exuberant case of glenohumeral synovial chondromatosis with extra-articular extension

Description 

A 27-year-old man presented with a history of 4-year duration of mechanical pain in the left shoulder and a progressive reduction in the range of movements. In the physical examination stands out a swelling of stony consistency on the posterior aspect of the left arm, pain with all active and passive movements of the left shoulder associated with limitation of active and passive abduction above 90°.

The blood tests were normal. The X-ray of the left shoulder showed multiple calcified intra-articular and extra-articular loose bodies (figure 1).

Figure 1

Conventional left shoulder radiography: multiple calcified intra-articular and extra-articular bodies.

A shoulder MRI was ordered demonstrating exuberant expansion of all joint spaces and recesses from the glenohumeral interface to the subcoracoid and subscapularis recess and along the tendon sheath of the long portion of the biceps, which suggested cartilaginous nature with...

https://ift.tt/2Nq3n0S

Recurrent chikungunya retinitis

Chikungunya is a systemic viral disease transmitted to humans by infected mosquitoes in endemic areas of Africa, Asia and more recently in the Americas. Chikungunya infection produces a sudden onset of fever, joint pains and erythematous skin eruption. A plethora of ocular manifestations have been described ranging from a non-specific conjunctivitis to exudative retinal detachment. Ocular chikungunya seems to respond well to corticosteroid therapy, and outcomes are usually better if treated early. Our patient acquired this infection on a travel to Mexico jungle. This was confirmed by ReverseTranscriptase-PCR test once she returned to the UK. The peculiarity of the case is the inordinate delay of almost a year in the onset of eye symptoms, from acquiring the viral infection. The ocular inflammation responded to systemic corticosteroid therapy with a favourable visual outcome. She developed a recurrence many months later which again responded well to a course of oral steroids.

https://ift.tt/2wicjyv

Red, white and blues: Darier disease and mood disorder

Description 

A middle-aged woman presented with a progressively worsening rash for 25 years. The rash was foul smelling and tender, occurring symmetrically in the folds of her abdomen and lower legs. Her medical history was significant for major depressive disorder. She had been receiving care from multiple psychiatrists over the last 10 years, and she has been hospitalised in inpatient psychiatric facilities for acute psychotic episodes. She admitted to having two of five siblings with similar skin problems, both additionally having been diagnosed with mood disorders including bipolar disorder and major depressive disorder. The patient stated the other three siblings were healthy. On examination, the patient had plaques of confluent papules and foul-smelling, weeping patches which were distributed over the folds of her chest and abdomen, as well as the flexure surfaces of her bilateral lower extremities (figure 1). Examination of her nails revealed red and white...

https://ift.tt/2Pcv91n

Amyloidosis: a unifying diagnosis for nephrotic syndrome and congestive cardiac failure

Diagnosing patients simply with heart failure or nephrotic syndrome is insufficient, and clinicians should always search for the underlying causes of these syndromes. Amyloidosis represents a rare group of diseases in which abnormal protein, namely amyloid fibrils, build up in various organs. Presentation depends on which organ systems are involved, and symptoms could include breathlessness associated with fluid overload suggestive of cardiac and/or renal involvement and diarrhoea and weight loss, suggestive of gastrointestinal involvement. The authors present a case of congestive cardiac failure and nephrotic range proteinuria in a patient with persistent fluid overload secondary toamyloid light-chain (AL) amyloidosis.

https://ift.tt/2wiS6sG

Unusual case of dasatinib-associated acute bilateral hyphemas leading to blindness in a patient with chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is a myeloproliferative disorder with an incidence of 1–2 cases per 100 000 adults per year.¹ Since the International Randomized Study of Interferon and STI571 trial (IRIS trial) in 2003, treatment with tyrosine kinase inhibitors (TKIs) has become the standard of care for patients with newly diagnosed CML in the chronic phase.² Dasatinib is a second-generation TKI and is generally well tolerated, with cytopenias, gastrointestinal (GI) symptoms and fluid retention being the most commonly observed side effects.^3–5 Bleeding complications, although unusual, have been reported with dasatinib, with an incidence ranging from 8% to 24%.^3–6 The most commonly reported site of bleeding is the GI tract.^{3 5} We report an unusual case of dasatinib-associated bleeding presenting with acute bilateral hyphemas, which, to our knowledge, is the first report of its kind.

https://ift.tt/2PcuWeB

Resolution of bulbar and spinal symptoms postcranial dural arteriovenous fistula embolisation

Dural arteriovenous fistulas (DAVF) are uncommon lesions. Multiple classification systems have been proposed to attempt to describe these lesions. We describe the case of a patient with a dorsal epidural DAVF that, while cerebral in origin, presented with classic spinal DAVF symptoms. Following embolisation, the patient had complete radiographic and symptomatic resolution. Classification of these DAVFs by embryological development allows for potential stratification of DAVFs with a different biological aetiology and diverse characteristics to more fully understand disease mechanisms.

https://ift.tt/2wh90aQ

Chronic thromboembolic pulmonary hypertension: an enigma

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary arterial hypertension (PAH) in which the pulmonary thrombus fails to resolve, resulting in occlusion and remodelling of pulmonary arteries.¹ Timely diagnosis is critical since it is potentially curable by pulmonary thromboendarterectomy. Twenty five per cent of cases do not have a history of thromboembolic event. The diagnosis should be considered in the diagnostic work-up of PAH despite lack of history of episodes of thromboembolism. Here we are reporting a case of CTEPH with multiple systemic to pulmonary collaterals delineated by angiogram and CT.

https://ift.tt/2Pbhes7

Additional distal femoral osteotomy for insufficient correction after high tibial osteotomy

A 70-year-old man who was treated with a closed-wedge high tibial osteotomy (HTO) had recurrent right medial knee pain 12 years after the initial osteotomy. We planned a recorrection osteotomy because the patient led an active lifestyle, had well-preserved range of motion and the lateral compartment was still intact. According to preoperative deformity analysis, which indicated a tibia in slight valgus and a femur in moderate varus, recorrection of the distal femur was chosen. Seven degrees of biplanar distal femoral osteotomy (DFO) was performed using a contralateral version of the TomoFix Medial Distal Femur. At 1 year follow-up, the femorotibial angle had improved from 178° to 170°, and the Japanese Orthopaedic Association score had improved from 75 to 95 points. Additional DFO could be a viable alternative for total knee arthroplasty or recorrection HTO when the centre of the deformity is located at the distal femur.

https://ift.tt/2whMy1l

Challenging case of an intramedullary tibial abscess in the setting of chronic osteomyelitis

Description 

This is the case of a 43-year-old wheelchair-user man with a history of hepatitis C, cirrhosis, intravenous drug abuse and a 2-year history of chronic right lower extremity ulcers who presented to the emergency department with 4 days of worsening right leg pain. On physical exam, there was a new area of fluctuance on the anterior tibial surface. Labs included a white cell count of 9.3 K/µL, C reactive protein of 129 mg/L and erythrocyte sedimentation rate of 90 mm/hour. A CT scan demonstrated proximal tibia osteomyelitis with an intramedullary abscess, surrounding soft tissue abscesses and septic arthritis of the knee joint (figure 1).

Figure 1

(A) Permeative appearance of the proximal tibial metaphysis and diaphysis with areas of cortical lucency and endosteal scalloping, suspicious for osteomyelitis. (B) Intramedullary fluid collection within the proximal tibial metaphysis/epiphysis, containing hyperattenuating contents with two punctate foci of air measuring approximately 6.7x4.7x16.6 cm,...

https://ift.tt/2Nolq7u

Tubular adenomas of the breast: a rare diagnosis

Tubular adenomas of the breast are rare benign tumours and few cases have been reported. Most often, the tumours are described as palpable, well-circumscribed masses in women of childbearing age and are commonly diagnosed as fibroadenomas both clinically and radiographically. Surgical excision is required for diagnosis and to prevent continuing growth. Here, we present two cases of these rare tumours, both with unusual presentations. The first case describes a very large specimen (10 cm x 9.5 cm x 4 cm mass) with tubular adenoma pathology, which is one of the largest reported in medical literature. The second case illustrates another rare specimen, a mixture of both tubular adenoma and fibroadenoma pathology. We elected to document these cases to assist in the management of these rare lesions. Our hope is that this will allow future physicians to better identify and treat the pathology with improved outcomes for these patients.

https://ift.tt/2whui8m

Weeping Leg'

Description 

A 37-year-old daily wager from Uttar Pradesh in Northern India presented with multiple painless small nodules and granules discharging sinuses over the left leg. The lesions were uniformly distributed below the knee up to the ankle crease (figure 1). The skin was puckered and tethered to the underlying tissues. However, the foot and thigh of the involved limb and rest of the other limbs were absolutely symptom free. Radiographs showed erosion of the entire tibia and fibula with mixed sclerotic and osteolytic areas (figure 2, black arrows) along with sub tissue swelling and periosteal reactions (figure 2, white arrows). The culture of the grains  in Modified Sabouraud Agar media supplemented with 0.5% yeast extract revealed Madurella mycetomatis from its characteristic colony of fruiting bodies.

Figure 1

Clinical photograph of the left leg of the patient showing multiple discharging sinuses with...

https://ift.tt/2Nj3KKq

Documented vancomycin-induced severe immune-mediated thrombocytopaenia

A 69-year-old man developed Propionibacterium acnes left knee hardware infection after suffering from an infected ingrown toenail. The hardware was removed and he was treated with intravenous vancomycin. Ten days after initiation of vancomycin, he developed severe thrombocytopaenia, epistaxis and petechiae. Vancomycin was discontinued, and platelets rapidly recovered. Serum vancomycin IgG were positive. Patient completed a 6-week course of ceftriaxone with no further complications.

https://ift.tt/2wcPTPp

Opioid toxicity with underlying tumour lysis syndrome in a patient with CMML: a diagnostic and therapeutic challenge

Use of strong opioids like morphine as analgesics for painful conditions in haematological malignancies is a challenging task. We report a unique case of chronic myelomonocytic leukaemia presenting with opioid toxicity overlapping with tumour lysis syndrome. The patient was on hydroxyurea-based chemotherapy for the primary disease. She was receiving oral morphine for abdominal pain due to splenomegaly. She was brought to the emergency in unresponsive state with pinpoint pupils. Opioid overdose leading to unconsciousness was suspected as the first diagnosis. Further workup revealed a final diagnosis of tumour lysis syndrome overlapping with opioid overdose. The patient was ventilated and started on naloxone infusion, and supportive measures for managing tumour lysis were added. The patient gradually improved and was extubated on the fifth day of ventilation. This case presents several learning points for the treating physician. Haematological malignancies have a dynamic course of disease with waxing and waning tumour burden during the course of chemotherapy. This fact should be kept in mind when prescribing strong opioids like morphine on outpatient basis to these patients. Massive tumour cell lysis during the course of chemotherapy may precipitate tumour lysis syndrome and may lead to renal dysfunction which makes the patient susceptible to morphine-related adverse effects. Pain physician should keep a watch for therapy-related adverse effects to avoid diagnostic and therapeutic dilemma associated with coexisting features of these two fatal conditions.

https://ift.tt/2P9Nj3z

Novel microguidewire-assist (MGA) manoeuver for coil embolisation of an unruptured middle cerebral artery aneurysm

We describe here a novel yet very simple technique, called microguidewire-assist (MGA) manoeuvre, for coil embolisation of unruptured intracranial aneurysms. A 79-year-old woman with a small, broad-necked middle cerebral artery (MCA) bifurcation aneurysm that incorporated the orifice of the acute-angled M2 superior trunk underwent coil embolisation. Since the balloon assist technique was not feasible, we inserted and retained only the microguidewire through M1 to the M2 superior trunk; subsequently, with appropriate use of the microguidewire, coil embolisation was completed. The MGA manoeuvre resulted in slight vessel straightening and subsequent changes in the angulation of the aneurysmal neck, with which stable placement of the platinum coil was successfully accomplished. For coil embolisation of small, broad-necked MCA aneurysms that partially straddle the M2 trunk, this manoeuvre might provide an effective therapeutic alternative if other techniques are not feasible.

https://ift.tt/2wjzPv9

Short stature and growth hormone deficiency: unexpected manifestations of McCune-Albright syndrome

McCune-Albright syndrome (MAS) is a rare disease characterised by triad of monostotic or polyostotic fibrous dysplasia, café au-lait skin spots and a variety of endocrine disorders; precocious puberty (PP) being the most common presenting symptom in female patients. Hyperfunction endocrinopathies including hyperthyroidism, growth hormone excess and cortisol excess are typical presentations in MAS. We present a case of 21-year-old woman with clinical and radiological characteristics of MAS triad; she presented with short stature which was attributed to both growth hormone deficiency and PP. Growth hormone deficiency in MAS has not been reported in English medical literature.

https://ift.tt/2P89CXC

Cobb syndrome (cutaneomeningospinal angiomatosis)

Description 

A 62-year-old woman was referred to the orthopaedic oncology service for evaluation of a bleeding and enlarging soft tissue mass along the right anterior abdominal wall. She had a lifelong history of a cutaneous and subcutaneous vascular malformation, affecting the right lateral chest and right abdomen and extending proximally to involve the mid-thoracic spine. Her medical history was significant for a prior aborted attempted surgical resection of the vascular malformation in 1980 due to intraoperative bleeding. Her history also included L4–L5 laminectomy without fusion for lower extremity weakness without radicular symptoms in 1989 and coil embolisation of a T9 epidural fistula in 2011 to prevent any abnormal vascular flow. Examination of the bilateral lower extremity showed marked steppage gait with bilateral external rotation deformities and bilateral foot drop. Motor examination of the lower extremities revealed muscle power grading of 1/5 extensor hallucis longus bilaterally, 2/5 tibialis anterior...

https://ift.tt/2whue8C

Anti-AMPA receptor encephalitis associated with Medullary thyroid cancer

AMPA receptor (AMPAR) antibodies are a group of recently discovered antibodies which target the neuronal synaptic proteins causing B-cell (immune) mediated neuronal damage, resulting in various neurologic syndromes depending on the area of central nervous system involvement. These syndromes are mostly reversible if treated early. Tumour association has been reported in up to 60% of cases in the most recent case series with lung, breast, ovarian cancers and thymomas being the most commonly associated malignancies with these antibodies. We present here the first case of AMPAR encephalitis associated with medullary thyroid cancer. Our patient presented with cognitive dysfunction and behavioural changes over a period of 3 weeks, with a full recovery after starting immunotherapy, once the diagnosis of AMPAR limbic encephalitis was established. This case highlights the importance of early diagnosis and management of AMPAR encephalitis as these patients respond well to immunotherapy and can have an almost complete recovery.

https://ift.tt/2P8gnsc

Good vibrations: itch induction by whole body vibration exercise without the need of a pruritogen

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


https://ift.tt/2PEl6D0

Granulysin, a novel marker for extranodal NK/T cell lymphoma, nasal type

Abstract

Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression.

https://ift.tt/2PcgUcV

The Application of Fluorescence Laparoscopy in the Treatment of Adenocarcinoma of the Esophagogastric Junction

Conditions:   Fluorescence Laparoscopy;   Adenocarcinoma of the Esophagogastric Junction
Interventions:   Procedure: fluorescent laparoscopic radical gastrectomy;   Procedure: traditional laparoscopic radical gastrectomy
Sponsor:   Dong Yang
Not yet recruiting

https://ift.tt/2oeE9rf

Lesion Dosimetry With Iodine-124 in Metastatic Thyroid Carcinoma

Conditions:   Thyroid Carcinoma;   Metastatic Thyroid Carcinoma
Interventions:   Device: PET/CT Scan;   Drug: Iodine-124
Sponsor:   Memorial Sloan Kettering Cancer Center
Recruiting

https://ift.tt/2BR2jl9

EBV-TCR-T（YT-E-001） for Patients With EBV-positive Recurrent or Metastatic NPC Patients

Condition:   Nasopharyngeal Carcinoma
Intervention:   Biological: EBV-TCR-T (YT-E001) cells
Sponsors:   Fujian Cancer Hospital;   China Immunotech Co., Ltd.
Not yet recruiting

https://ift.tt/2oe2VaQ

Pain in Parkinson's Disease With Motor Fluctuations.

Condition:   Parkinson Disease
Interventions:   Drug: safinamide metansolfonato (12 weeks);   Drug: rasagilina mesilato (12 weeks)
Sponsors:   Universita di Verona;   Azienda Ospedaliera Universitaria Integrata Verona
Recruiting

https://ift.tt/2BSKbHG

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

Condition:   Thyroid Cancer, Medullary
Interventions:   Drug: 177Lu-PP-F11N;   Drug: Sacuitril
Sponsors:   University Hospital, Basel, Switzerland;   Krebsforschung Schweiz, Bern, Switzerland;   Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland;   University Hospital, Zürich;   University Hospital Freiburg
Not yet recruiting

https://ift.tt/2okImK9

Predictor Analysis of Acute Radiation Oral Mucositis in NPC Patients Treated With IMRT/TOMO Combined Chemotherapy

Condition:   Nasopharyngeal Carcinoma
Intervention:  
Sponsor:   Zhejiang Cancer Hospital
Recruiting

https://ift.tt/2BSK276

Widespread keratosis pilaris in a patient with Noonan syndrome with multiple lentigines

International Journal of Dermatology, EarlyView.


https://ift.tt/2obKnrP

Resveratrol and ivacaftor are additive G551D CFTR‐channel potentiators: therapeutic implications for cystic fibrosis sinus disease

International Forum of Allergy &Rhinology, EarlyView.


https://ift.tt/2wgcgn2

Case of histiocytosis with bone involvement of fingers successfully treated with peginterferon‐α

The Journal of Dermatology, EarlyView.


https://ift.tt/2Luk6hq

Congenital nail clubbing

The Journal of Dermatology, EarlyView.


https://ift.tt/2MTHD0h

Treatment of psoriasis and psoriatic arthritis with secukinumab after unsatisfactory response to ustekinumab in multiple sclerosis patient

The Journal of Dermatology, EarlyView.


https://ift.tt/2Lwj6cO

Case of anaphylaxis caused by black ginger in a dietary supplement

The Journal of Dermatology, EarlyView.


https://ift.tt/2MTHycZ

Evaluation of epicardial adipose tissue volume and coronary artery calcification in Japanese patients with psoriasis vulgaris

The Journal of Dermatology, EarlyView.


https://ift.tt/2NjLMHF

Case of anaphylaxis to lansoprazole confirmed by histamine release test and oral provocation test

The Journal of Dermatology, EarlyView.


https://ift.tt/2MVV9Am

Sandmückenfieber – eine „vernachlässigte“ Krankheit

Zusammenfassung

Eine 45-jährige Patientin stellte sich mit Fieber, Durchfall, Gliederschmerzen, allgemeinem Krankheitsgefühl und einem juckenden papulösen Exanthem in der Ambulanz eines tropenmedizinischen Zentrums zur weiteren Diagnostik vor. Sie hatte zuvor 11 Tage Urlaub mit ihrer Familie in einem Bergdorf in Nordzypern gemacht. Dort habe es sehr viele kleine, stechende Fliegen oder Mücken gegeben. Nach der Rückkehr erkrankten sie und ihre Familie. Die körperliche Untersuchung war bis auf das Exanthem an den Beugeseiten der Extremitäten unauffällig. In der Routineblutuntersuchung fielen eine deutliche Erhöhung der Transaminasen und ein nur geringfügig erhöhtes C‑reaktives Protein (CRP) auf. Unter Berücksichtigung des Reiselandes, des Hinweises auf die „stechenden Fliegen" und der Klinik wurde in die differenzialdiagnostischen Überlegungen zur Ursache der Hepatitis auch das sog. Sandmückenfieber einbezogen. Es konnten Antikörper gegen das sizilianische Sandmückenfiebervirus (SFSV) nachgewiesen werden, die im Verlauf eine typische Dynamik zeigten, sodass die Diagnose eines Pappataci-Fiebers gestellt wurde. Die Kasuistik und eine kurze Zusammenstellung von Informationen über den Erreger, den Vektor, die Epidemiologie, Klinik, Diagnostik und Therapiemöglichkeiten sollen dazu anregen, Phlebovirusinfektionen als mögliche Differenzialdiagnose zu berücksichtigen, wenn Reisende oder Flüchtlinge nach Aufenthalt im Mittelmeerraum an schweren fieberhaften Erkrankungen mit Hepatitis und Hauterscheinungen oder aseptischen viralen Meningitiden erkranken.

https://ift.tt/2Lvf30g

Probe‐based confocal laser endomicroscopy for diagnosis of nasopharyngeal carcinoma in vivo

The Laryngoscope, EarlyView.


https://ift.tt/2ogs4S9

Free Flap Versus Pedicled Flap Reconstruction of Laryngopharyngeal Defects: A 10‐Year National Surgical Quality Improvement Program Analysis

The Laryngoscope, EarlyView.


https://ift.tt/2Pak6FF

Laryngeal Cryptococcoma Resulting in Airway Compromise in an Immunocompetent Patient: A Case Report

The Laryngoscope, EarlyView.


https://ift.tt/2oco9WD

Long‐term analysis of transorally resected p16 + Oropharynx cancer: Outcomes and prognostic factors

The Laryngoscope, EarlyView.


https://ift.tt/2PbwQw1

Sarcomatoid Carcinoma in the Parotid Gland: A Review of 30 Years of Experience

The Laryngoscope, EarlyView.


https://ift.tt/2odTU1s

Do All Patients With Head and Neck Cancer Require a Positron Emission Tomography Scan at Diagnosis?

The Laryngoscope, EarlyView.


https://ift.tt/2PaFZVs

A novel approach to skull‐base and orbital osteotomies through virtual planning and navigation

The Laryngoscope, EarlyView.


https://ift.tt/2MxLNM3

HPV status in unknown primary head and neck cancer: Prognosis and treatment outcomes

The Laryngoscope, EarlyView.


https://ift.tt/2PaFQ4m

Rhinosinusitis symptoms, smoking and COPD: prevalence and associations

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


https://ift.tt/2PHa67T

Allergen immunotherapy as add-on to biologic agents

Purpose of review In this review, we sought to outline many of the recent evidences about the available clinical trials in which biologic agents [i.e. omalizumab (OMA)] were associated as add-on to allergen-specific immunotherapy (AIT). Recent findings The available literature shows that OMA may be a valuable option as add-on to AIT for respiratory allergy, or food desensitization, especially in the escalation or build-up phases, in which adverse events are more commonly expected. The encouraging data for hymenoptera venom allergy remain limited to case reports, and no structured clinical trial is available. Summary Over the past decade, studies of OMA used with AIT have shown promising results. Today, big randomized, double-blind, placebo-controlled trials are needed to better select those patients who would benefit from the addition of OMA (or other biologic agents) to AIT, as well as optimal dosing schedules, optimal duration of treatments and, finally, adequate evaluation about pharmacoeconomic aspects. Correspondence to Carlo Lombardi, MD, Departmental Unit of Allergology & Pneumology, Fondazione Poliambulanza Hospital, Brescia, Italy. Tel: +39 030 3518555; e-mail: carlo.lombardi@poliambulanza.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PDqnuy

Office-based surgery and patient outcomes

Purpose of review The purpose of this review is to provide an update on the current knowledge about patient safety and outcomes in the office-based setting. Ambulatory procedures performed outside the hospital are steadily increasing, resulting in an increasing number and complexity of office-based procedures and patient comorbidities over the past two decades. In this review we focus on most recent outcomes studies encompassing different surgical specialties and patient populations. Recent findings Rates of complications in the office-based surgical (OBS) setting from the latest publications are similar to, or better than previously reported studies. Many of the studies published were in the field of plastic surgery, with a few publications on office vascular and dental procedures. The most common complications were haematomas, infections and venous thromboembolisms (VTE)s and pulmonary emboli. Death was a rare finding, though when it occurred, it was often associated with VTE/pulmonary emboli and abdominoplasties. Summary Overall, these studies contribute positively to the safety of office-based anaesthesia. As an increasing number of procedures migrate from the hospital setting to ambulatory and office-based environments, it will be critically important to continue ensuring patients are well tolerated. Correspondence to Richard D. Urman, MD, MBA, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Tel: +1 617 732 8222; e-mail: Rurman@bwh.harvard.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2MxJg4v

Allergen immunotherapy as add-on to biologic agents

Purpose of review In this review, we sought to outline many of the recent evidences about the available clinical trials in which biologic agents [i.e. omalizumab (OMA)] were associated as add-on to allergen-specific immunotherapy (AIT). Recent findings The available literature shows that OMA may be a valuable option as add-on to AIT for respiratory allergy, or food desensitization, especially in the escalation or build-up phases, in which adverse events are more commonly expected. The encouraging data for hymenoptera venom allergy remain limited to case reports, and no structured clinical trial is available. Summary Over the past decade, studies of OMA used with AIT have shown promising results. Today, big randomized, double-blind, placebo-controlled trials are needed to better select those patients who would benefit from the addition of OMA (or other biologic agents) to AIT, as well as optimal dosing schedules, optimal duration of treatments and, finally, adequate evaluation about pharmacoeconomic aspects. Correspondence to Carlo Lombardi, MD, Departmental Unit of Allergology & Pneumology, Fondazione Poliambulanza Hospital, Brescia, Italy. Tel: +39 030 3518555; e-mail: carlo.lombardi@poliambulanza.it Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PDqnuy