No abstract available
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Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 12 Φεβρουαρίου 2018
Intensive Care Unit Enhanced Recovery Pathway for Patients Undergoing Orthotopic Liver Transplants Recipients: A Prospective, Observational Study
BACKGROUND: Liver transplant recipients continue to have high perioperative resource utilization and prolonged length of stay despite improvements in perioperative care. Enhanced recovery pathways have been shown in other surgical populations to produce reductions in hospital resource utilization. METHODS: A prospective, observational study was performed to examine the effect of an enhanced recovery pathway for postoperative care after liver transplantation. Outcomes from patients undergoing liver transplantation from November 1, 2013, to October 31, 2014, managed by the pathway were compared to transplant recipients from the year before pathway implementation. Multivariable regression analysis was used to assess the association of the clinical pathway on clinical outcomes. RESULTS: The intervention and control groups included 141 and 106 patients, respectively. There were no demographic differences between the control and intervention group including no differences between the length of surgery and cold ischemic time. Median intensive care unit length of stay was reduced from 4.4 to 2.6 days (P
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Congenital Langerhans cell histiocytosis presenting in a 27-week-gestation neonate
Abstract
Langerhans cell histiocytosis is exceedingly rare in premature infants, and the few cases reported suggest a poor prognosis with systemic involvement. We present a case of Langerhans cell histiocytosis limited to a single cutaneous lesion, presenting in a 27-week-gestation infant, which is the youngest gestational age of reported Langerhans cell histiocytosis cases. The lesion showed spontaneous resolution by 41 weeks corrected gestational age, and systemic involvement was absent, demonstrating a mild course of skin-only Langerhans cell histiocytosis in a premature infant.
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Subacute cutaneous lupus erythematosus presenting in twins
Abstract
Subacute cutaneous lupus erythematosus is a clinically distinct form of cutaneous lupus erythematosus, with age of onset typically in the second to fifth decades. Eleven cases have been reported in childhood, and we present the first known case of subacute cutaneous lupus erythematosus in identical twins. Although flares are typically photo-induced, we present an annular eruption typical of subacute cutaneous lupus erythematosus with concurrent pinworm infestation, with recurrence of disease with cutaneous larva migrans. The patient's identical twin had a similar eruption with pinworm infection. This case highlights the possibility of parasitic infestation as a trigger for subacute cutaneous lupus erythematosus in genetically susceptible individuals.
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Bascule syndrome associated with syncopal episodes
Abstract
Bascule syndrome is a recently described benign vasomotor dermatosis characterized by Bier anemic spots, cyanosis, and urticaria-like eruption. We report a case of a 13-year-old girl with cutaneous lesions consistent with Bascule syndrome who had had three exercise-related syncopal episodes. It would be recommended to exclude orthostatic intolerance or postural orthostatic tachycardia syndrome when evaluating patients with Bascule syndrome.
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Geographic tonguelike presentation in a child with pityriasis rosea: Case report and review of oral manifestations of pityriasis rosea
Abstract
Oral lesions are rarely reported in patients with pityriasis rosea. We report a case of a 3-year-old boy with clinical evidence of generalized pityriasis rosea who developed asymptomatic oral lesions similar in appearance to geographic tongue. The generalized eruption and tongue lesions resolved simultaneously within 4 weeks. We also review the literature on the oral manifestations of Pityriasis rosea.
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Parental use of sun protection for their children—does skin color matter?
Abstract
Background/Objectives
Excessive sun exposure during childhood is a risk factor for skin cancer. This study aimed to compare the frequency of ideal sun protection use between parents with lighter- and darker-skinned children and explore their attitudes and beliefs on sun safety and their choice of sun protection.
Methods
Parents of children aged 6 months to 6 years completed self-administered questionnaires about sun protection practices for their children. Parents assessed their child's Fitzpatrick phototype and were divided into lighter- (Fitzpatrick phototype I-III) and darker-skinned (Fitzpatrick phototype IV-VI) groups. Sun safety guidelines from the Canadian Dermatology Association were used to qualify ideal sun protection.
Results
A total of 183 parents were included. Overall, 31 parents (17%) used ideal sun protection for their children. As their children grew older, parents were less likely to use ideal sun protection (odds ratio = 0.69, 95% confidence interval = 0.53-0.90). Parents in the lighter-skinned group were more likely to use ideal sun protection for their children (odds ratio = 7.4, 95% confidence interval = 2.7-20.1), believe that sun exposure was harmful (odds ratio = 17.2, 95% confidence interval = 4.0-74.9), and perceive value in sun protection (odds ratio = 11.4, 95% confidence interval = 3.3-39.0); the darker-skinned group believed that darker skin tones provided more sun protection (odds ratio = 12.4, 95% confidence interval = 6.1-25.4).
Conclusion
Ideal parental sun protection efforts are overall low, particularly in parents of darker-skinned children. The identified attitudes toward and beliefs about sun safety may aid in delivery of future sun protection interventions, especially in multiracial populations.
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Treatment outcomes of vitiligo in Asian children
Abstract
This retrospective study aimed to identify factors that predict treatment response in a cohort of Asian children with vitiligo. Shorter duration of vitiligo was associated with better repigmentation. Patients with focal vitiligo of short duration have a good chance of achieving repigmentation with topical agents alone.
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Pediatric Intracranial Hypertension: a Current Literature Review
Abstract
Purpose of Review
The purpose of this review is to provide an update on pediatric intracranial hypertension.
Recent Findings
The annual pediatric incidence is estimated at 0.63 per 100,000 in the USA and 0.71 per 100,000 in Britain. The Idiopathic Intracranial Hypertension Treatment Trial found improvement in visual fields, optical coherence tomography, Frisen grade, and quality of life with acetazolamide compared to placebo in adult patients, and these findings have been translated to the pediatric population.
Summary
Pediatric intracranial hypertension is a disorder that if left untreated can lead to poor quality of life and morbidity. There are no current treatment studies in pediatrics, but adult data suggests acetazolamide remains an acceptable first-line medication.
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Skin lesions serve as clues to relapse of pediatric blastic plasmacytoid dendritic cell neoplasm
Abstract
A 10-year-old girl with a history of blastic plasmacytoid dendritic cell neoplasm, a rare malignancy in children, presented with recurrent skin eruptions beginning while on maintenance chemotherapy, including mildly pruritic skin-colored plaques, tender indurated nodules, and violaceous bound-down plaques. This case highlights an unusual presentation of relapsed blastic plasmacytoid dendritic cell neoplasm on chemotherapy, with skin lesions providing important clues to the progression of systemic disease.
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Maternal Thyrotropin Receptor Antibody Concentration and the Risk of Fetal and Neonatal Thyrotoxicosis: A Systematic Review
Thyroid Feb 2018, Vol. 28, No. 2: 257-264.
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Rapid Remission of Graves' Hyperthyroidism Without Thionamides Under Immunosuppressive Treatment for Concomitant Autoimmune Hepatitis
Thyroid Feb 2018, Vol. 28, No. 2: 276-278.
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SIRT1-Regulated Abnormal Acetylation of FOXP3 Induces Regulatory T-Cell Function Defect in Hashimoto's Thyroiditis
Thyroid Feb 2018, Vol. 28, No. 2: 246-256.
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Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective Study
Thyroid Feb 2018, Vol. 28, No. 2: 229-235.
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Time-resolved fluorescence spectroscopy for the diagnosis of oral lichen planus
Summary
Background
Lichen planus (LP) is a T-cell mediated autoimmune disorder of unknown aetiology that affects the skin, nails, oral and genital mucous membranes. Conventionally, oral LP (OLP) is diagnosed through clinical assessment and histopathological confirmation by oral biopsy.
Aim
To explore the use of time-resolved fluorescence spectroscopy (TRFS) to detect fluorescence lifetime changes between lesional OLP and perilesional normal mucosa.
Methods
In this pilot study, measurements of lesional and perilesional buccal and mouth floor mucosa were conducted in vivo with a TRFS system. Histopathological findings were consistent with OLP in 8 out of 10 patients biopsied. Two patients with histopathological diagnoses of frictional hyperkeratosis and oral candidiasis, respectively, were excluded from the study.
Results
Our preliminary data show that lifetime values in the 360–560 nm spectral range indicate a significant differentiation between normal and diseased tissue. In contrast to the standard oral biopsy procedure, this technique is noninvasive, painless, time-efficient and safe.
Conclusions
Future studies are needed to better elucidate the diagnostic capability of TRFS and to further explore the sources of fluorescence contrast. This pilot study suggests that, based on fluorescence lifetime parameters, TRFS is a very promising technology for the development of a novel OLP diagnostic technique.
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Clinical outcomes and prognostic factors in cisplatin versus cetuximab chemoradiation for locally advanced p16 positive oropharyngeal carcinoma
Publication date: April 2018
Source:Oral Oncology, Volume 79
Author(s): Christian L. Barney, Steve Walston, Pedro Zamora, Erin H. Healy, Nicole Nolan, Virginia M. Diavolitsis, Anterpreet Neki, Robert Rupert, Panos Savvides, Amit Agrawal, Matthew Old, Enver Ozer, Ricardo Carrau, Stephen Kang, James Rocco, Theodoros Teknos, John C. Grecula, Jessica Wobb, Darrion Mitchell, Dukagjin Blakaj, Aashish D. Bhatt
ObjectivesRandomized trials evaluating cisplatin versus cetuximab chemoradiation (CRT) for p16+ oropharyngeal cancer (OPC) have yet to report preliminary data. Meanwhile, as a preemptive step toward morbidity reduction, the off-trial use of cetuximab in p16+ patients is increasing, even in those who could potentially tolerate cisplatin. The purpose of this study was to compare the efficacy of cisplatin versus cetuximab CRT in the treatment of p16+ OPC and to identify prognostic factors and predictors of tumor response.Materials and methodsCases of p16+ OPC treated with cisplatin or cetuximab CRT at our institution from 2010 to 2014 were identified. Recursive partitioning analysis (RPA) classification was used to determine low-risk (LR-RPA) and intermediate-risk (IR-RPA) groups. Log-rank/Kaplan-Meier and Cox Regression methods were used to compare groups.ResultsWe identified 205 patients who received cisplatin (n = 137) or cetuximab (n = 68) CRT in the definitive (n = 178) or postoperative (n = 27) setting. Median follow-up was 3 years. Cisplatin improved 3-year locoregional control (LRC) [92.7 vs 65.4%], distant metastasis-free survival (DMFS) [88.3 vs 71.2%], recurrence-free survival (RFS) [86.6 vs 50.6%], and overall survival (OS) [92.6 vs 72.2%] compared to cetuximab [all p < .001]. Concurrent cisplatin improved 3-year OS for LR-RPA (97.1 vs 80.3%, p < .001) and IR-RPA (97.1 vs 80.3%, p < .001) groupings.ConclusionWhen treating p16+ OPC with CRT, the threshold for substitution of cisplatin with cetuximab should be maintained appropriately high in order to prolong survival times and optimize locoregional and distant tumor control. When cetuximab is used in cisplatin-ineligible patients, altered fractionation RT should be considered in an effort to improve LRC.
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Laryngeal recurrence sites in patients previously treated with transoral laser microsurgery for squamous cell carcinoma
Abstract
Background
The laryngeal framework provides a natural barrier preventing tumour spread to extralaryngeal structures. Transoral laser microsurgery (TLM) for laryngeal squamous cell carcinoma (SCC) may violate these boundaries, altering the pathways of tumor spread for potential recurrences. Our project objective is to describe laryngeal SCC recurrence patterns and overall survival in patients requiring total laryngectomy (TL) after TLM.
Methods
Patients undergoing TLM for laryngeal SCC requiring salvage TL were identified from a prospective CO2 laser database containing all patients undergoing TLM for head and neck malignancies at the QEII Health Sciences Center in Halifax, Nova Scotia between March 2002 – May 2014. Surgical pathology reports were analyzed for tumor characteristics, extent of recurrence and invasion of local structures. Kaplan-Meier analyses were performed to evaluate overall survival, disease specific survival (DSS) and locoregional control.
Results
Fifteen patients were identified from the database as receiving salvage TL for recurrent disease after initial TLM resection for laryngeal SCC. Final pathology reports demonstrated that 67% (10/15) of patients had thyroid cartilage involvement while 53% (9/15) of patients had cricoid cartilage involvement on salvage TL pathology. 33% (5/15) of patients had perineural invasion and 27% (4/15) had lymphovascular invasion. Mean and median follow-up times were 36.7 months and 26.8 months respectively (range 3.9–112.6). The Kaplan-Meier estimate for overall survival at 36 months was 40% post TL with a standard error (SE) of 13.6%. DSS was 47% (SE 14.2%), and locoregional control was 55% (SE 14.5%) post TL.
Conclusions
Laryngeal recurrence sites following TLM seem to be consistent with historical data at known laryngeal sites of vulnerability. Treatment with TLM does not predispose patients to a lower rate of locoregional control and overall survival after total laryngectomy and salvage outcomes are consistent with literature values.
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pSTM6-275, a conjugative IncHI2 plasmid of Salmonella that confers antibiotic and heavy metal resistance under changing physiological conditions [PublishAheadOfPrint]
Detailed annotation of an IncHI2 plasmid, pSTM6-275, from Salmonella enterica serotype 1,4,5,12:i:- TW-Stm6 revealed a composite structure including antimicrobial resistance genes on mobile genetic elements. The plasmid was thermosensitive for transfer to E.coli and conferred reduced susceptibility to antibiotics, copper sulphate and silver nitrate. Metal ion susceptibility was dependent on physiological conditions, giving an insight into the environments where this trait might confer a fitness advantage.
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Prediction model for anti-malarial activities of hemozoin inhibitors using physicochemical properties [PublishAheadOfPrint]
The rapid spread of strains of malaria parasites resistant to several drugs has threatened global malaria control. Hence, the aim of this study was to predict the anti-malarial activity of chemical compounds possessing anti-hemozoin formation activity as a new means of anti-malarial drug discovery. After the initial in vitro anti-hemozoin formation high-throughput screening (HTS) of 9,600 compounds, a total of 224 hit compounds were identified as hemozoin inhibitors. These 224 compounds were tested for in vitro erythrocytic anti-malarial activity at 10 μM using the chloroquine-mefloquine sensitive Plasmodium falciparum strain, 3D7A. Two independent experiments were conducted. The physicochemical properties of the active compounds were extracted from ChemSpider and SciFinder databases. We analyzed the extracted data using Bayesian model averaging (BMA). Our findings revealed that lower numbers of S atoms, lower values of log D pH 3, 4 and 5, and higher values of ACD log D pH 7.4 had a significant association with anti-malarial activity among compounds possessing anti-hemozoin formation activity. The BMA model revealed an accuracy of 91.23%. We report new prediction models containing the physicochemical properties that shed light on effective chemical groups for synthetic anti-malarial compounds and help in silico screening for novel anti-malarial drugs.
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Novel zinc attenuating compounds as potent broad spectrum antifungal agents with in vitro and in vivo efficacy. [PublishAheadOfPrint]
An increase in the incidence of rare but hard-to-treat invasive fungal pathogens as well as resistance to the currently available antifungal drugs calls for new broad-spectrum antifungals with a novel mechanism of action. Here, we report the identification and characterization of two novel zinc-attenuating compounds ZAC307 and ZAC989, which exhibit broad-spectrum in vitro antifungal activity and in vivo efficacy in a fungal kidney burden candidiasis model.
The compounds were identified serendipitously as part of a drug discovery process aimed at finding novel inhibitors of the fungal plasma membrane proton ATPase, Pma1. Based on their structure, we hypothesized that they might act as zinc chelators. Indeed, both fluorescence-based affinity determination and potentiometric assays revealed these compounds, subsequently termed zinc attenuating compounds (ZACs), to have strong affinity for zinc, and their growth inhibitory effects on Candida albicans and Aspergillus fumigatus could be inactivated by the addition of exogenous zinc to fungal growth media. We determined the ZACs to be fungistatic, with a low propensity for resistance development. Gene expression analysis suggested that the ZACs interfere negatively with the expression of genes encoding the major components of the A. fumigatus zinc uptake system, thus supporting perturbance of zinc homeostasis as the likely mode of action. Taken together, with demonstrated in vitro and in vivo antifungal activity, low propensity for resistance development, and a novel mode of action, the ZACs represent a promising new class of antifungal compounds, and their advancement in a drug development program is therefore warranted.
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Efficacy of systemically administered polymyxins in mouse burn wound infection caused by multidrug-resistant Gram-negative pathogens: A proof-of-concept study [PublishAheadOfPrint]
The efficacy of subcutaneously administered polymyxins against burn wound infections caused by Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae was examined in a murine infection model. Subcutaneously administered colistin and polymyxin B achieved a >2-log10 reduction in the bacterial load for P. aeruginosa and A. baumannii infections, while wound infections by K. pneumoniae were less responsive (<1-log10 reduction). This study highlights the potential therapeutic benefits of parenteral polymyxins for treating burn wound infections.
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Inactivation of Plasmepsin 2 and 3 sensitizes Plasmodium falciparum to the antimalarial drug piperaquine [PublishAheadOfPrint]
Dihydroartemisinin-piperaquine (DHA-PPQ), the current frontline artemisinin combination therapy used to treat Plasmodium falciparum malaria in multiple Southeast Asian countries is now increasingly failing in Cambodia where artemisinin resistance is nearly fixed which suggests that PPQ resistance has emerged and is spreading rapidly in the Greater Mekong Subregion. Recent reports have shown that amplification of Plasmepsins 2 and 3 is a molecular marker of PPQ resistance however whether these enzymes play a role in the mechanism of resistance is currently unknown. We here show that inactivating Plasmepsin-2 or Plasmepsin-3 individually in the 3D7 P. falciparum reference strain results in hyper-susceptibility to PPQ. Interestingly, no significant differences in the susceptibility to other antimalarials were observed which suggests specific roles of Plasmepsin 2 and 3 in PPQ susceptibility. The piperaquine hyper-sensitivity of the Plasmepsin 2 and 3 inactivated lines provides direct evidence that these enzymes modulate parasite susceptibility to PPQ in the context of a single copy of PfMDR1 and independent of Kelch13 mutations conferring ART resistance.
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The Pharmacokinetics of 2000 mg Ertapenem in Tuberculosis Patients [PublishAheadOfPrint]
Ertapenem is a carbapenem antibiotic with activity against Mycobacterium tuberculosis. Dose simulations in a hollow fiber infection model showed that 2000 mg once daily is an appropriate dose to be tested in clinical studies. Before using this dose in a phase II study, the aim of this prospective pharmacokinetic study is to confirm the pharmacokinetics of 2000 mg once daily in TB patients. Twelve TB patients received a single intravenous dose of 2000 mg ertapenem as 30-min infusion. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 8, 12 and 24 hours post administration. Drug concentrations were measured using a validated LC-MS/MS assay. A large inter-individual variation in the pharmacokinetics of ertapenem was observed. The median (IQR) area under the plasma concentration-time curve to infinity (AUC (t=) (h*mg/l)) was 2032 (1751 – 2346) mg*h/L, the inter-compartmental clearance (CL12) 1.941 (0.979 – 2.817) L/h and the volume of distribution in the central compartment (V1) 1.514 (1.064 – 2.210) L. A more than dose-proportional increase in AUC was observed comparing the results to reported 1000 mg ertapenem in MDR-TB patients. Based on a minimal inhibitory concentration (MIC) of 1.0 mg/L, 11 out of 12 patients would have reached the target value of unbound drug exceeding the MIC over 40% of time (f40% T>MIC). In conclusion, this study shows that 2000 mg ertapenem once daily in TB patients reached the expected f40% T>MIC for most of the patients and exploration in a phase 2 study can be advocated.
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The coexistence of two blaNDM-5 genes on an IncF plasmid as revealed by nanopore sequencing [PublishAheadOfPrint]
In a carbapenem-resistant Escherichia coli clinical isolate of sequence type 167, two copies of blaNDM-5 were found on a 144,225-bp IncF self-transmissible plasmid of the F36:A4:B- type. Both blaNDM-5 genes were located in 11,065-bp regions flanked by two copies of IS26. The two regions were identical in sequence but were present at different locations on the plasmid, suggesting a duplication of the same region. This study highlights the complex genetic contexts of blaNDM-5.
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Susceptibility of clinical isolates of Trichomonas vaginalis to metronidazole and secnidazole--an in vitro study [PublishAheadOfPrint]
Nitroimidazoles (metronidazole [MTZ] and tinidazole [TNZ]) are the only drugs recommended for treating Trichomonas vaginalis (TV) infection. MTZ resistance occurs in 4%–10% of cases of vaginal trichomoniasis (1, 2), and TNZ resistance in 1% of patients (2). Emerging nitroimidazole-resistant trichomoniasis is concerning because few alternatives to standard therapy exist. We assessed the prevalence of in vitro aerobic MTZ and secnidazole resistance among TV isolates from 100 women in Birmingham, AL with positive cultures during the period 2015-2016.. Archived specimens were treated with secnidazole or MTZ (0.2–400 μg/mL) for 48 hours, as per the United States Centers for Disease Control and Prevention protocols. Ninety-six of the 100 clinical trichomonas isolates tested (96%) demonstrated a lower minimal lethal concentration for secnidazole than for MTZ, suggesting that secnidazole has better in vitro activity than MTZ.
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A next-generation sequencing and bioinformatics protocol for Malaria drug Resistance marker Surveillance (MaRS) [PublishAheadOfPrint]
The recent advances in next-generation sequencing technologies provide a new and effective way of tracking malaria drug resistant parasites. To take advantage of this technology an end-to-end Illumina targeted amplicon deep sequencing (TADS) and bioinformatics pipeline for molecular surveillance of drug resistance in P. falciparum, called Malaria Resistance Surveillance (MaRS), was developed. TADS relies on PCR enriching genomic regions, specifically target genes of interest, prior to deep sequencing. MaRS enables researchers to simultaneously collect data on allele frequencies of multiple full-length P. falciparum drug resistance genes (crt, mdr1, k13, dhfr, dhps, and cytochrome b) as well as the mitochondrial genome. Information is captured at the individual patient level for both known and potential new single nucleotide polymorphisms associated with drug resistance. MaRS pipeline was validated using 245 imported malaria cases that were reported to the Centers for Disease Control and Prevention (CDC). The chloroquine resistant crt CVIET genotype was observed in 42% of samples, the highly pyrimethamine resistant triple mutant dhps IRN in 92% of samples, and the sulfadoxine resistant dhps SGEAA in 26% of samples. The mdr1 NFSND genotype was found in 40% of samples. With the exception of two cases imported from Cambodia, no artemisinin resistant K13 alleles were identified and 99% of patients carried parasites susceptible to atovaquone-proguanil. Our goal is to implement MaRS at the CDC for routine surveillance of imported malaria cases in the U.S. and aid in the adoption of this system in participating state public health laboratories as well as global partners.
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Sofosbuvir and Ribavirin Liver Pharmacokinetics in Patients Infected with Hepatitis C Virus [PublishAheadOfPrint]
Sofosbuvir and ribavirin exert their anti-hepatitis C virus (HCV) activity following metabolic activation in the liver. However, intrahepatic concentrations of the pharmacologically active nucleotide metabolites in humans are poorly characterized due to the inaccessibility of tissue and technical challenges with measuring nucleotide levels. A clinical study assessing the efficacy of sofosbuvir and ribavirin administered prior to liver transplant to prevent HCV reoccurrence provided a unique opportunity to quantify nucleotide concentrations in human liver. We analyzed nucleotides using high performance liquid chromatography coupled to tandem mass spectrometry in liver tissue from 30 HCV-infected patients with hepatocellular carcinoma who were administered sofosbuvir (400 mg/day) and ribavirin (1,000-1,200 mg/day) for between 3 and 52 weeks prior to liver transplantation. Median total hepatic metabolite concentrations (sum of nucleoside and mono-, di-, and tri-phosphates) were 77.1 μM for sofosbuvir and 361 μM for ribavirin in patients on therapy at the time of transplant. Ribavirin and sofosbuvir efficiently loaded the liver, with total hepatic concentrations exceeding maximal plasma levels by approximately 30-fold. Ribavirin metabolite levels suggest its monophosphate is in great excess of its inhibition constant for inosine monophosphate dehydrogenase and triphosphate is approaching the binding constant for incorporation by the HCV NS5B RNA-dependent RNA polymerase. Consistent with the potent antiviral activity of sofosbuvir, these results illustrate that liver triphosphate levels achieved following sofosbuvir administration greatly exceed the inhibition constant for HCV NS5B. In conclusion, this study expands the quantitative understanding of the pharmacology of sofosbuvir and ribavirin by establishing efficient hepatic delivery in the clinic.
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Pharmacodynamics of Voriconazole for Invasive Pulmonary Scedosporiosis [PublishAheadOfPrint]
Scedosporium apiospermum is a medically important fungal pathogen that causes a wide range of infections in humans. There are relatively few antifungal agents that are active against Scedosporium spp. Little is known about the pharmacodynamics of voriconazole against Scedosporium. Both static and dynamic in vitro models of invasive scedosporiosis were developed. Monoclonal antibodies that target a soluble cell wall antigen secreted by Scedosporium apiospermum were used to describe the pharmacodynamics of voriconazole. Mathematical pharmacokinetic-pharmacodynamic models were fitted to the data to estimate the drug exposure required to suppress the release of fungal antigen. The experimental results were bridged to humans using Monte Carlo simulation. All 3 strains of S. apiospermum tested invaded through the cellular bilayer of the in vitro models and liberated antigen. There was a concentration-dependent decline in antigen with near maximal antifungal activity in all 3 strains with 10 mg/L. Similarly, there was a drug exposure dependent decline in circulating antigen in the dynamic model and complete suppression of antigen with an AUC of approximately 80 mg.h/L. A regression of the AUC:MIC versus area under the antigen time curve showed that near maximal effect was obtained with AUC:MIC of approximately 100. Monte Carlo simulation suggested that only isolates with an MIC of 0.5 mg/L enable pharmacodynamic targets to be acheived with a standard regimen of voriconazole. Isolates with higher MICs may need higher drug exposure targets than are currently recommended for other fungi.
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Anidulafungin pharmacokinetics in ascites and pleural effusion of critically ill patients [PublishAheadOfPrint]
Anidulafungin concentrations were quantified with high pressure liquid chromatography (HPLC) and UV detection in ascites and in pleural effusion of ten adult critically ill patients. Samples were collected from ascites and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulafungin levels in ascites (0.12-0.99 μg/ml) and in pleural effusion (0.32-2.02 μg/ml) were below the simultaneous plasma levels (1.04-7.70 and 2.48-13.36 μg/ml, respectively) and below the MIC values of several pathogenic Candida strains.
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A Phase 1 Study in Healthy Subjects to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Oral Doses of DS-2969b, a Novel GyrB Inhibitor [PublishAheadOfPrint]
DS-2969b is a novel GyrB inhibitor in development for the treatment of Clostridium difficile infection (CDI). The aim of this study was to assess the safety, tolerability, pharmacokinetics, and effects on normal gastrointestinal microbiota of multiple daily oral ascending doses of DS-2969b in healthy subjects. The study enrolled three sequential ascending dose cohorts (60 mg, 200 mg, and 400 mg). In each cohort, subjects received an oral dose of DS-2969b or placebo (six DS-2969b and two placebo) each morning for 14 days. DS-2969b was safe and well tolerated at all dose levels examined. All adverse events related to DS-2969b were mild, and predominantly related to the gastrointestinal tract. DS-2969a (free form of DS-2969b) plasma concentrations increased with increasing doses, however, both Cmax and AUC increased less than dose-proportionally. In all cohorts, sufficient fecal levels of DS-2969a were achieved within 24 hours following the administration of the first dose and maintained for at least 17 days. Following treatment with DS-2696b, a clear reduction in Clostridium coccoides and Bifidobacterium groups was observed. However, populations of three other bacterial groups examined (Bacteroides fragilis, Clostridium leptum, and Prevotella) were not affected. Data from this study support and encourage further development of DS-2969b as a novel treatment for CDI.
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Omadacycline: comparative in vitro activity against dog and cat bite wound isolates [PublishAheadOfPrint]
Omadacycline was tested against 125 isolates recovered from infected cat and dog bites in humans. Its activity was similar to other compounds in the tetracycline class and was active against strains exhibiting tetracycline resistance. Against anaerobic isolates, resistance to tetracyclines was more prominent, and omadacycline was the most active of the group. All isolates had omadacycline MICs <1 μg/ml with the exception of Eikenella corrodens which showed reduced susceptibility to the entire tetracycline group.
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Probing the Mechanism of Inactivation of the FOX-4 Cephamycinase by Avibactam [PublishAheadOfPrint]
Ceftazidime-avibactam is a "second generation" β-lactam-β-lactamase inhibitor combination that is effective against Enterobacteriaceae expressing class A extended-spectrum β-lactamases, class A carbapenemases and/or class C cephalosporinases. Knowledge of the interactions of avibactam, a diazabicyclooctane with different β-lactamases is required to anticipate future resistance threats. FOX family β-lactamases possess unique hydrolytic properties with a broadened substrate profile to include cephamycins, partly as a result of an isoleucine at position 346, instead of the conserved asparagine found in most AmpCs. Interestingly, a single amino acid substitution at N346 in the Citrobacter AmpC is implicated in resistance to the aztreonam-avibactam combination. In order to understand how diverse active site topologies affect avibactam inhibition, we tested a panel of clinical Enterobacteriaceae isolates producing blaFOX using ceftazidime-avibactam, determined the biochemical parameters for inhibition using the FOX-4 variant, and probed the atomic structure of avibactam with FOX-4. Avibactam restored susceptibility to ceftazidime for most isolates producing blaFOX; two isolates expressing blaFOX-4 or blaFOX-5 displayed an MIC of 16 μg/mL for the combination. FOX-4 possessed a k2/K value of 1,800 ± 100 M-1s-1 and a koff of 0.0013 ± 0.0003 s-1. Mass spectrometry showed that the FOX-4-avibactam complex was stable for 24 hr. Analysis of the crystal structure of FOX-4 with avibactam at a 1.5 Å resolution revealed a unique characteristic of this AmpC β-lactamase. Unlike in the PDC-1 avibactam crystal structure, interactions (e.g., hydrogen bonding) between avibactam and position I346 in FOX-4 are not evident. Furthermore, another residue is not observed to be close enough to compensate for the loss of these critical hydrogen bonding interactions. This observation supports findings from the inhibition analysis of FOX-4; FOX-4 possessed the highest Kd value (1,600 nM) for avibactam compared to other AmpCs (7-660 nM). Medicinal chemists must consider the properties of extended-spectrum AmpCs, such as the FOX β-lactamases for the design of future diazabicyclooctanes.
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In vitro and in vivo activities of DS-2969b, a novel GyrB inhibitor, against Clostridium difficile [PublishAheadOfPrint]
DS-2969b is a novel GyrB inhibitor, which is currently under clinical development for treatment of Clostridium difficile infection (CDI). In this study, the in vitro and in vivo activities of DS-2969b were evaluated. DS-2969b inhibited the supercoiling activity of C. difficile DNA gyrase. DS-2969b showed potent in vitro activity against C. difficile clinical isolates with an MIC90 of 0.06 μg/mL, which was 2-, 32-, and 16-fold lower than the MIC90 of fidaxomicin, vancomycin, and metronidazole, respectively. DS-2969b did not select spontaneous resistant mutant of various C. difficile strains at 4 x MICs and the frequency of resistance development was less than 4.8 x 10-9. In a hamster CDI model, 5-day oral administration of DS-2969b conferred complete protection from recurrence and mortality at 0.3 mg/kg once a day compared with 50% survival rate with fidaxomicin at 3 mg/kg once a day and 0% with vancomycin at 50 mg/kg/dose twice a day. Even a single oral administration of 1 mg/kg of DS-2969b in the CDI model exhibited 100% animal survival without recurrence. DS-2969b was also efficacious by 5-day subcutaneous administration in the CDI model. DS-2969b showed similar fecal excretion after intravenous and oral administrations in rats. These data support further development of DS-2969b as a drug for oral and intravenous treatment of CDI.
http://ift.tt/2o2lI8N
In Vitro and In Vivo Efficacy of a Novel and Long Acting Fungicidal Azole, PC1244 on Aspergillus fumigatus Infection [PublishAheadOfPrint]
The antifungal effects of the novel triazole, PC1244, designed for topical or inhaled administration, against A. fumigatus have been tested in a range of in vitro and in vivo studies. PC1244 demonstrated potent antifungal activities against clinical A. fumigatus isolates (N=96) with a MIC range of 0.016--0.25 μg/ml, whereas the MIC range for voriconazole was 0.25--0.5 μg/ml. PC1244 was a strong tight-binding inhibitor of recombinant A. fumigatus CYP51A and CYP51B (sterol 14α-demethylase) enzymes and strongly inhibited ergosterol synthesis in A. fumigatus with an IC50 of 8 nM. PC1244 was effective against a broad spectrum of pathogenic fungi (MIC ranged from <0.0078~2 μg/ml), especially on Aspergillus terreus, Trichophyton rubrum, Candida albicans, Candida glabrata, Candida krusei, Cryptococcus gattii, Cryptococcus neoformans and Rhizopus oryzae. PC1244 also proved to be quickly absorbed into both A. fumigatus hyphae and bronchial epithelial cells, producing persistent antifungal effects. In addition, PC1244 showed fungicidal activity (MFC, 2 μg/ml), which was 8-fold more potent than voriconazole. In vivo, once daily intranasal administration of PC1244 (3.2 ~ 80μg/mL) to temporarily neutropenic, immunocompromised mice 24h after inoculation with itraconazole-susceptible A. fumigatus substantially reduced fungal load in the lung, galactomannan in serum and circulating inflammatory cytokines. Furthermore, 7 days extended prophylaxis with PC1244 showed superior in vivo effects when compared against 1 day of prophylactic treatment, suggesting accumulation of the effects of PC1244. Thus, PC1244 has the potential to be a novel therapy for the treatment of A. fumigatus infection in the lungs of humans.
http://ift.tt/2nSVTIX
In vitro activity of lascufloxacin against Streptococcus pneumoniae with mutations in the quinolone resistance-determining regions (QRDRs) [PublishAheadOfPrint]
Lascufloxacin showed potent activity against Streptococcus pneumoniae with GyrA or ParC mutation (first-step mutants). The frequency of selecting resistant strains tended to be lower for lascufloxacin than levofloxacin and garenoxacin after drug exposure in first-step mutants, but was similar in the comparison between lascufloxacin and moxifloxacin. The increase in MIC was smaller for lascufloxacin than for levofloxacin, garenoxacin, and moxifloxacin when clinical strains with only ParC mutation were exposed to the corresponding drug.
http://ift.tt/2o2lu1r
Determinants of extreme ss-lactam tolerance in the Burkholderia pseudomallei complex [PublishAheadOfPrint]
Slow-growing bacteria are insensitive to killing by antibiotics, a trait known as antibiotic tolerance. In this study, we characterized the genetic basis of an unusually robust ß-lactam (meropenem) tolerance seen in Burkholderia species. We identified tolerance genes under three different slow-growth conditions by extensive transposon mutant screening (Tn-seq) followed by single mutant validation. There were three principle findings. First, mutations in a small number of genes reduced tolerance under multiple conditions. Most of the functions appeared to be specific to peptidoglycan synthesis and the response to its disruption by meropenem action rather than associated with more general physiological processes. Top tolerance genes are involved in immunity toward a Type VI toxin targeting peptidoglycan (BTH_I0069), peptidoglycan recycling (ldcA), periplasmic regulation by proteolysis (prc), and an envelope stress response (rpoE, degS). Second, most of the tolerance functions did not contribute to growth in the presence of meropenem (intrinsic resistance), indicating that the two traits are largely distinct. Third, orthologues of many of the top B. thailandensis tolerance genes were also important in B. pseudomallei. Overall, these studies show that the determinants of meropenem tolerance differ considerably depending on cultivation conditions, but that there are a few shared functions that have strong mutant phenotypes and are important in multiple Burkholderia species.
http://ift.tt/2nSVIxh
The In Vitro Activity of Omadacycline and Comparators Against Anaerobic Bacteria [PublishAheadOfPrint]
Omadacycline (OMC), a broad-spectrum aminomethylcycline, has shown clinical efficacy in anaerobic acute bacterial skin and skin structure infections (ABSSSI) and in animal models of intra-abdominal anaerobic infections. Here, the in vitro activity of OMC against clinically-relevant anaerobes was similar to tigecycline, with MIC90 values of 1 to 8 μg/mL against Bacteroides spp, 0.5 μg/mL against Clostridium difficile, Prevotella spp., and Porphyromonas asaccharolytica, 1 μg/mL against Peptostreptoccus spp., and 16 μg/mL against C. perfringens.
http://ift.tt/2o2lluV
Reply to: “Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials”
I want to thank Dr Rieder1 for drawing attention to the challenges faced by brodalumab. I agree with nearly all the points made, although I hope Dr Rieder's prediction that the Risk Evaluation and Mitigation Strategies (REMS) program will doom this drug prove to be untrue.
http://ift.tt/2nVdNe0
To fee or not to fee? The ethical issues of concierge medicine/dermatology
Concierge medicine is an emerging practice model that involves direct contracting with patients for medical services, often charging a flat monthly or yearly fee. There is considerable variation among concierge practices, but most include administrative service fees with an upfront annual payment to remain on a smaller patient panel.1
http://ift.tt/2nWRIvx
An open-label exploratory study evaluating the efficacy and safety of ingenol mebutate gel 0.05% for the treatment of verruca vulgaris
To the Editor: Current therapies for common warts (verruca vulgaris) often require months of treatment and focus on destruction, removal of callus, or stimulation of a local immune response.1-3 Topical use of ingenol mebutate gel, 0.05%, indicated for the treatment of actinic keratosis, induces necrosis and an inflammatory reaction.4 A recent case study series provided evidence for the efficacy of ingenol mebutate against anogenital warts.5
http://ift.tt/2o0kBWQ
Frontal fibrosing alopecia and cutaneous comorbidities: A potential relationship with rosacea
To the Editor: Frontal fibrosing alopecia (FFA) is an increasingly prevalent lymphocytic, cicatricial alopecia with a yet unknown etiopathogenesis. Some cutaneous diseases have been associated with FFA, but the existing literature is limited to retrospective studies and case reports.1-3 The objective of our study was to analyze the frequency of associated cutaneous conditions in a large cohort of FFA patients.
http://ift.tt/2nV5Up2
A cross-sectional study of YouTube videos about atopic dermatitis
To the Editor: Patients are increasingly looking to online platforms for health information.1 One popular online platform is YouTube, which is a free video-streaming service. The loose content regulations of YouTube allow users to broadcast false information as easily as accurate information. One study found that most of the YouTube videos about tanning beds portrayed them in a positive light and another found that half of YouTube videos on immunizations did not explicitly support them.2,3 We conducted a cross-sectional study on the information on YouTube about atopic dermatitis (AD) by performing 5 searches on YouTube using the search terms "atopic dermatitis," "eczema," "eczema tips," "eczema cure," and "eczema treatment." We screened the first 2 pages of results for inclusion.
http://ift.tt/2o2J4uP
Reply to: “The microbial flora of taxane therapy–associated nail disease in cancer patients”
See related letter on page 607
http://ift.tt/2nVkxbS
Response to: “Maintenance of Certification: A grandfatherly ethical analysis”
See related article on page 627
http://ift.tt/2o2IUUf
Crown vessels and follicular white dot: New dermoscopic findings in a case of solitary reticulohistiocytoma
A 17-year-old girl presented with 2-month history of solitary progressively enlarging asymptomatic 6- × 6-mm light pink-yellow nontender dome-shaped nodule over her left cheek with surface scaling, a solitary violaceous area, and peripheral telangiectasia (Fig 1).
http://ift.tt/2nVjqci
Referral patterns to an osteoporosis clinic for dermatology patients undergoing prolonged corticosteroid therapy
To the Editor: Glucocorticoids are frequently used in dermatology. Glucocorticoid-induced osteoporosis (GIOP) is a well-recognized side effect with substantial morbidity. GIOP prevention measures are essential for bone health. Studies have shown dermatologists are underutilizers of bisphosphonates, first-line agents for osteoporosis prevention.1 A high-risk osteoporosis clinic (HIROC) developed by the rheumatology department was established at the Geisinger Medical Center. This retrospective cohort study reviewed dermatology patients taking oral glucocorticoids for more than 30 consecutive days to determine referral patterns to the HIROC, completion rate of referrals, and follow-up interventions.
http://ift.tt/2o2SXsl
In response to Lebwohl et al, “Psychiatric adverse events during treatment with brodalumab: Analysis of psoriasis clinical trials”
To the Editor: I would like to commend Lebwohl et al for their thorough and transparent analysis of the psychiatric adverse events associated with the brodalumab trials.1 One of the first systemic agents for psoriasis to be examined in a study enrolling a population with no specific psychiatrically related exclusion criteria, brodalumab in some ways fell victim to its own noble aims. In retrospect, it should not have been unexpected that a trial enrolling a large cohort of middle-aged white men with moderate-to-severe psoriasis, some of whom had additional suicide risk factors, resulted in several episodes of suicidal ideation and behavior (SIB).
http://ift.tt/2o3eoJR
The microbial flora of taxane therapy–associated nail disease in cancer patients
See related letter on page e71
http://ift.tt/2o1klXL
Reconstruction of Tragus and External Auditory Meatus using Remnant Auricle during Microtia Reconstruction
Facial plast Surg
DOI: 10.1055/s-0037-1617436
This article investigates an effective method with which to reconstruct the tragus and external auditory meatus for microtia reconstruction. The external ear was reconstructed using a delayed postauricular skin flap in patients with congenital microtia. After the first stage of delaying the postauricular skin flap and the second stage of otoplasty with ear framework fabricated from autogenous rib cartilage draping with the delayed skin flap, the third stage involved tragus and external auditory meatus canaloplasty. After designing the remnant auricle flap, the lower part was trimmed and the tragus was reconstructed. The upper part was trimmed into a thin skin flap, which was rotated and used to cover the hollowed wound posterosuperior to the tragus so as to mimic the external auditory meatus. If remnant wounds were present, skin grafting was conducted. In total, 121 patients with congenital microtia were treated from March 2010 to March 2016. The reconstructed tragus and external auditory meatus were well formed, and all wounds healed well. No severe complications such as flap necrosis occurred. Six months postoperatively, the morphology of the reconstructed tragus and external auditory meatus was good. Overall, the patients and their families were satisfied. The use of remnant auricle to reconstruct the tragus and external auditory meatus is an effective auricular reconstruction technique.
[...]
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2Bq5r5B
Alum-adjuvanted allergoids induce functional IgE-blocking antibodies
Abstract
The only therapy that is able to modulate the cause of IgE-mediated allergy and to attain a long-term effect is allergen-specific immunotherapy (AIT). In conventional subcutaneous AIT, the vaccine consists of an extract from an allergen source that contains major and minor allergens as well as non-allergenic proteins. To reduce IgE-mediated side effects caused by the injection of intact allergens, chemically modified extracts with less IgE-binding activity, named allergoids, have been used for AIT since the 1980′s.
This article is protected by copyright. All rights reserved.
http://ift.tt/2ElgJXw
Johns Hopkins Brings Therapy Dogs into ICU
In an editorial that draws on results of previously published studies and experiences in their medical intensive care unit (ICU), a team of Johns Hopkins Medicine professionals say that bringing specially trained dogs into ICUs can safely and substantially ease patients' physical and emotional suffering.
http://ift.tt/2H9Z9HH
Differences in gene expression profile between vocal cord Leukoplakia and normal larynx mucosa by gene chip
Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. Vocal cord leukoplakia is a precancerous lesion in otolaryngological practice. Till now, the expression patterns and functions of lncRNAs...
http://ift.tt/2Enjtnl
Utility and Versatility of the Supraclavicular Artery Island Flap in Head and Neck Reconstruction
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): José A. González-García, Carlos M. Chiesa-Estomba, Jon A. Sistiaga, Ekhiñe Larruscain, Leire Álvarez, Xabier Altuna
IntroductionThe supraclavicular island flap is a rotational pedicled flap and may have some advantages in head and neck reconstruction compared with free-tissue transfer when this kind of reconstruction is not affordable or recommended.Material and methodsWe present our experience during the year 2016 in the application of the supraclavicular island flap in five cases as an alternative to microvascular reconstruction in several defects after resection of head and neck tumours. In two patients, the flap was used to close the surgical pharyngostoma after total laryngectomy with partial pharyngectomy. In one patient, it was used in lateral facial reconstruction after partial resection of the temporal bone. In one case, it was used to close a skin defect after total laryngectomy with prelaryngeal tissue extension. And in the last case to close a neck skin defect after primary closure of a pharyngo-cutaneous fistula. There were no flap complications, and the result was satisfactory in all cases.ResultsThe supraclavicular artery island flap is useful and versatile in head and neck reconstruction. Operating room time in aged patients or those with comorbidities will be reduced compared to free flaps. The surgical technique is relatively easy and can be used for skin and mucosal coverage.ConclusionThe supraclavicular island flap could be a recommended option in head and neck reconstruction, its use seems to be increasing and provides a safe and time-saving option to free flaps in selected patients.
http://ift.tt/2EyGabD
Application of Flexible Endoscopy-Based Biopsy in the Diagnosis of Tumour Pathologies in Otorhinolaryngology
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Carlos Saga, Manuel Olalde, Ekhiñe Larruskain, Leire Álvarez, Xabier Altuna
Introduction and objectivesInterventional endoscopy allows us to act on the pathology of the patient with minimal discomfort, low costs and high efficiency. We assessed the validity of flexible endoscopic biopsies in our hospital, in lesions suspected of malignancy in the rhino-pharyngo-laryngeal space.Subjects and methodsRetrospective study of patients with a pathology suspected of malignancy assessed between 2006 and 2016 in our centre. We evaluated the effectiveness, the tolerance and the number of complications. We calculated the cost reduction in comparison with direct laryngoscopy in the operating room. We compared our sample with others of similar characteristics described in the literature.ResultsThirty patients were studied with a flexible endoscopic biopsy during that period. Nineteen patients obtained positive results which allowed them to start treatment for their pathology. Seven cases had no evidence of malignancy and required another biopsy under general anaesthesia, which confirmed the carcinoma diagnosis. Two samples ruled out malignancy which was confirmed by laryngeal microsurgery. One case showed inflammation and the lesion was cured after antibiotherapy. It was impossible to collect the sample in one case. Thus, we obtained sensitivity levels of 73% with a specificity of 100%. There were no complications. The cost reduction in our sample was above 80%.ConclusionsFlexible endoscopic biopsy has advantages over direct laryngoscopy that are relevant in the diagnosis of oncological pathology in otorhinolaryngology.
http://ift.tt/2slO5nu
Accuracy of FNAC and CT in the Differentiation of Benign and Malignant Parotid Tumours in a Case Series
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Marina A. Gavín-Clavero, Tomás Usón-Bouthelier, Úrsula M. Jariod-Ferrer, Arancha Fernández-Larrañaga, Bianca Pantilie, Fernando Lobera-Molina, M. Victoria Simón-Sanz, Bartolomé Nadal Cristóbal
IntroductionParotid tumours, in addition to the wide variety of types, are histologically complex. Differentiating between benign and malignant tumours in preoperative diagnosis is important in deciding the type of surgery required. Fine needle aspiration cytology (FNAC) is a simple, quick, low-cost, low-invasive and well-tolerated tool used in the preoperative diagnosis of these tumours.Material and methodswe calculated the sensitivity, specificity, predictive positive value (PPV) and negative predictive value (NPV) of FNAC and computed tomography (CT) in the differentiation of benign and malignant parotid tumours operated between 2010 and 2014 in the oral and maxillofacial surgery department of the University Hospital Miguel Servet.ResultsThe sensitivity of FNAC is 50%, while the specificity is high, at 98.7%. FNAC offers high reliability in the diagnosis of malignant tumours, despite its low sensitivity. However, when the diagnosis is indeterminate or benign, other than pleomorphic adenoma or Whartin tumour, the reliability to exclude malignancy decreases.ConclusionThe low sensitivity of FNAC to differentiate malignant from benign parotid tumours, means that we cannot rule out other diagnostic tests, clinical symptoms and especially the intraoperative vision of each surgeon. Especially when the diagnosis is indeterminate. Nevertheless, it is a technique used in a systematised way and helps in pre-surgical decision-making.
http://ift.tt/2EBQuzv
Inlay Butterfly Miringoplasty. Our Experience
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Paula Cruz Toro, Ángela Callejo Castillo, Rafael Moya Martínez, Iván Domenech Juan
IntroductionMultiple surgical techniques have been proposed to close tympanic perforations. Eavey, two decades ago, described a technique aimed at closing central perforations in children. For this, he designed a butterfly-shaped cartilage graft that was placed between the tympanic membrane in an inlay manner. This technique showed great effectiveness for the closure of perforations as well as low morbidity, rapidity and great economic difference.MethodsWe performed a descriptive study of a series of cases analysing 32 interventions in children and adults with the modified Eavey technique, during the period from January 2012 to November 2016. We evaluated the surgical and audiometric functional results.ResultsSurgical success was achieved in 93% of cases, including complete closures in 27 patients (84%) and 3 cases in which minimal asymptomatic dehiscences occurred. There was rejection of the graft and persistence of the perforation in only one case. No major surgical or postoperative complications associated with the procedure were described. The mean improvement in the audiometric gap was from 17dB preoperatively to 7dB after the intervention.ConclusionsThe modified Eavey technique is a low morbidity, cost-effective procedure with a technical facility that proves effective for the closure of tympanic perforations in adults and children.
http://ift.tt/2sq1yuy
On ciprofloxacin concentration in chronic rhinosinusitis
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): José Gameiro dos Santos, Rosário Figueirinhas, José P. Liberal, João C. Almeida, Joana Sousa, Amílcar Falcão, Corália Vicente, João Paço, Cecília A. Sousa
ObjectiveConsidering that all the evidence indicates that chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are distinct entities, the aim of this study was to compare the concentrations obtained in plasma and in sinonasal mucosa with oral and nasal topical ciprofloxacin, in patients with and without nasal polyps, without evaluating the effectiveness of the use of an antibiotic.MethodsProspective clinical study with single-blind randomization. The population consisted of patients with chronic rhinosinusitis with eligible for endonasal surgery, over 18 years old. It took place between January 2010 and December 2014. A single preoperative dose of ciprofloxacin (oral or nasal topic- spray, gel or drops) was given and samples of plasma and nasal mucosa (inferior turbinate, middle turbinate, ethmoid and maxillary sinus) were collected prior to surgery. The plasma and mucosal ciprofloxacin concentrations were assayed with high performance liquid chromatography (HPLC) with fluorescence detection (FD).ResultsThe oral ciprofloxacin achieved better mucosal concentrations but had a significant plasmatic expression in all patients. None of the topical formulations achieved measurable ciprofloxacin plasmatic levels. Among the topical formulations, the gel had the best mucosal results, despite the existence of polyposis.
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Transoral laser microsurgery as standard approach to hypopharyngeal cancer survival analysis in a hospital based population
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Eduardo Breda, Raquel Catarino, Eurico Monteiro
ObjectiveCancer of the hypopharynx remains one of the most challenging chapters in head and neck oncology. The objective of this study is to ascertain the relevance of a transoral laser approach as a valid functional option for treatment of cancer of the hypopharynx in Portugal, and additionally, to confirm the reproducibility of survival and functional outcomes described in other reference centers.Subjects and methodsThe outcomes of 37 out of 60 patients presenting hypopharyngeal carcinoma primarily treated by TLM (transoral laser microsurgery) and neck dissection and or adjuvant treatment when needed, with curative intention in tertiary referral center, were retrospectively evaluated and compared with published results.ResultsThere were no patients in stage I. Three-year and five-year overall survival (Kaplan–Meier) were 83.5% and 63.5% for stage II (n=12), 57.1% (only 3-year overall survival evaluable for this stage) for stage III (n=7), and 53.1% and 39.8% for stage IVa (n=18), respectively. Five-year local control rates were 90% for stage II and 87.5% for stage IVa, respectively; only three-year local control rates were possible to evaluate for stage III, with a 100% control rate. Five-year total larynx preservation rate was 97.3%.ConclusionsTLM, alone or with neck dissection and adjuvant therapy, is a valid procedure for treatment of hypopharyngeal cancer in different stages. Furthermore, this kind of approach can be replicated in different oncologic centers with similar oncologic and functional results.
http://ift.tt/2srPSaH
Hypoglossal Nerve Stimulation Surgery for Obstructive Sleep Apnoea: Our Preliminary Experience
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Peter Baptista, Octavio Garaycochea, Laura Álvarez-Gómez, Juan Alcalde, Manuel Alegre, Elena Urrestarazu
The objective of this communication is to describe our preliminary results in upper airway stimulation surgery via hypoglossal nerve stimulation implantation for obstructive sleep apnoea. We describe 4 cases and the outcomes of the surgery were analysed using the Epworth scale, apnoea-hypopnoea index, minimal O2 Sat, average O2 Sat and snoring intensity. In all cases a significant reduction in Epworth scale values and apnoea-hypopnoea index were obtained (P<.05). The minimum and average oxygen saturation had better values after the surgery, however, there was no statistically significant difference. The snoring severity measured subjectively changed from "intense" to "absent" in all cases. The preliminary results obtained with the upper airway stimulation surgery via hypoglossal nerve stimulation showed objective and subjective improvement after the implant activation.
http://ift.tt/2EBMRtm
Inverted Papilloma of Middle Ear and Temporal Bone
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Ignacio Pla-Gil, Antonio Morant Ventura, Jaume Redondo Martínez, Jaime Marco Algarra
http://ift.tt/2sq1zyC
Silent sinus syndrome in children
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Francisco Rosa, Rosário Figueirinhas, Jorge Oliveira, Cecília Almeida e Sousa
http://ift.tt/2EEccmk
Cranio-cervical junction cerebrospinal fluid leak after microdebrider-assisted adenoidectomy – A rare case report
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Karthikeyan Ramasamy, Hemanth Vamanshankar, Sunil Kumar Saxena, Vignesh Karunakaran, Arun Alexander
http://ift.tt/2srZ8vC
A Rare Benign Tumour on the Dorsum Nasi
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Ignacio Pla-Gil, Pedro Segarra Cortés, Jaime Marco Algarra
http://ift.tt/2EB41Hv
Alagille's Syndrome: Hypoplasia of Posterior Semicircular Canals
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Alexandre Perez-Girbes, Miguel Mazón, Elena Pont
http://ift.tt/2sqeD7d
Comments on “Alveolar sarcoma of the parapharyngeal space: A case report”
Publication date: January–February 2018
Source:Acta Otorrinolaringologica (English Edition), Volume 69, Issue 1
Author(s): Ana María Cano-Valdez, Diana Brisa Sevilla-Lizcano, Abelardo Meneses-García
http://ift.tt/2EChFdi
Face-to-face anti-tobacco intervention lowered cotinine level in asthmatic children
To assess the effectiveness of "face-to-face" intervention we have decided to measure urine cotinine levels. The secondary end point was to assess the effect of anti-tobacco parental interventions in children with asthma on their lung function.
http://ift.tt/2sn6K2A
Safe and effective intradermal influenza vaccine desensitization for delayed influenza vaccine allergy
We report a case of an 18-year-old Japanese male with delayed hypersensitivity to influenza virus vaccine, who completed seven years of successful annual vaccine desensitization using intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone®, Intradermal, Sanofi Pasteur, Cambridge MA). Informed consent was obtained this repot. At four years of age, the patient was hospitalized for evaluation of possible compartment syndrome in Japan for his first reaction to the intramuscular influenza vaccine when large circumferential swelling developed over a period of 24-48 hours after vaccination, which was successfully treated with intravenous steroids.
http://ift.tt/2EzKTtw
Asthma mobile applications: are they ready for prime time?
We are moving rapidly into the era of digital healthcare, which includes mobile health applications, wearable devices, health information technology, telehealth and telemedicine, and personalized medicine. With the growth of the use of smartphones in the population, this has allowed for the rapid increase in the downloading and use of medical health applications. In June 2015, Krebs and Duncan did a cross sectional survey of 1604 mobile phone users in the US and found that slightly over half had downloaded a health-related mobile app.
http://ift.tt/2stABpM
Problems in anticoagulation of a patient with antibiotic treatment for endocarditis: interaction of rifampicin and vitamin K antagonists
The cytochrome P450 is a superfamily of isoenzymes that are responsible for the metabolism of many drugs. Significant changes in pharmacokinetics and drug interactions may be due to induction of hepatic cytochrome P450 enzymes. Rifampicin is a common inducer of CYP3A4. We report a case of a 57-year-old woman who was suspected for endocarditis and therefore treated with rifampicin. Due to previous mechanical aortic valve replacement, she also received phenprocoumon for anticoagulation. Although continuing anticoagulant therapy, antibiotic coadministration led to normal international normalised ratio (INR) level. Fifteen days after the treatment with rifampicin ended, INR returned to therapeutic level.
http://ift.tt/2nV0gmM
Respiratory symptoms of an abdominal origin
Description
A 75-year-old, fully dependent woman was sent to the emergency department due to a sudden onset of fever (38°C), polypnoea and dyspnoea. The patient had a history of Parkinson's disease and vascular dementia, making it impossible to cooperate in the medical interview. She was feverish, breathing rapidly, although haemodynamically stable and with peripheral oxygen saturation of over 95%. Blood tests showed increase in C-reactive protein (8.51 mg/dL), leucocytosis (13x109/L, 67% neutrophils and 23.1% lymphocytes) and slight hypokalaemia (3 mmol/L), without respiratory insufficiency in the arterial blood. Chest X-ray showed no clear infectious consolidation.
Acute tracheobronchitis was assumed, so she was given an antibiotic and potassium chloride and was discharged. The patient returned the next day without fever but with all of the other symptoms, adding to them prostration. She was still breathing rapidly but her abdomen was larger and tympanic, with noticeable pain while it was being palpated, adding therefore...
http://ift.tt/2o0TLhB
Basilar artery fenestration: an unusual possible cause of ischaemic stroke?
Basilar artery fenestration is an uncommon congenital dysplasia and may be associated with ischaemic stroke. We present a case of a previously healthy 36-year-old man who presented with vertigo and vomiting. MRI showed posterior circulation territory infarction. High-resolution magnetic resonance angiography revealed a slit-like fenestration in the basilar artery. This patient had no traditional vascular risk factors or aetiology of cryptogenic stroke. The patient recovered from his neurological deficit after antiplatelet therapy and was given prophylactic aspirin therapy. There was no recurrence of symptoms after 12 months of follow-up.
http://ift.tt/2nVJwMm
Propionibacterium acnes and Staphylococcus epidermidis olecranon bursitis/osteomyelitis: a case involving surgical and antibiotic treatment
This report describes a 63-year-old generally healthy male with septic olecranon bursitis caused by Propionibacterium acnes. The patient sustained a small laceration after striking the posterior aspect of his left elbow on a metal railing when he was at a public swimming pool. We concluded that P. acnes was not initially detected because cultures were only kept for 5 days. Consequently, initial antibiotic treatment failed. P. acnes and Staphylococcus epidermidis grew in a subsequent tissue culture. The infection did not respond to intravenous vancomycin although soft-tissue debridements were done. This likely reflected the presence of olecranon osteomyelitis (seen on MRI scans) in addition to inadequate treatment with this antibiotic in the setting of a polymicrobial infection. Eventually, the infection was eradicated with multiple soft-tissue debridements in addition to the continuation of vancomycin with daily intravenous piperacillin/tazobactam that was added for the final 4 weeks of antibiotic treatment.
http://ift.tt/2o0TGKP
Rhabdomyolysis: a rare complication of Hashimotos thyroiditis precipitated by statin therapy
Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis is the most common form of primary hypothyroidism. Muscular manifestations like weakness, pain, stiffness and elevated muscle enzymes have been noticed in hypothyroidism. Statins are also known to cause myositis and rhabdomyolysis. This is a case of a middle-aged man, on statin therapy, who presented with severe muscle aches and pain and was found to have rhabdomyolysis. Further evaluation revealed an underlying HT as the culprit for his condition. He was managed with intravenous fluids and levothyroxine along with cessation of statins, following which he improved.
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Withdrawn: Cutaneous larva migrans with pulmonaryinvolvement
Maslin D, Wallace M. Cutaneous larva migrans with pulmonary involvement. BMJ Case Rep. Published Online: 12 Jan 2018. doi: 10.1136/bcr-2017-223508.
With no admission of liability, BMJ has removed this article voluntarily at the request of the patient concerned.
http://ift.tt/2o2mORN
Improving the efficacy of PET-CT imaging in head and neck cancer management and surveillance through the multidisciplinary team: a multi-centre, retrospective cohort analysis of 51 patients
Abstract
- There has been a recent move towards image-guided surveillance of N2/N3 disease in HNSCC and neck dissection only in selected cases
- PET-CT demand is rising and alters management in a third of HNSCC patients
- PET-CT is expensive and can lead to unnecessary and harmful investigations, delaying treatment
- The MDT is significantly less likely to request an inappropriate PET-CT than the individual clinician
- Collaboration among specialists may minimise the ordering of inappropriate PET-CTs, reducing costs and improving patient safety and management
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Effects of treatment for psoriasis on circulating levels of leptin, adiponectin and resistin: a systematic review and meta-analysis
Abstract
Background
Metabolic syndrome, a risk factor of cardiovascular disease, is more common in psoriatic patients compared to general population. Circulating adipokine concentrations are altered in psoriatic patients and are suggested to represent the pathophysiologic link between psoriatic lesions and metabolic alterations.
Objectives
To systematically review the literature for studies that investigated possible differences in the circulating levels of leptin, adiponectin or resistin in psoriatic patients before and after any treatment intervention and meta-analyze the best evidence available.
Methods
Search was conducted in three databases (PubMed, Central, EMBASE). Eligible for the review were studies that have assessed leptin, adiponectin or resistin concentrations in patients with psoriasis before and after any topical or systemic treatment.
Result
After treatment, blood concentrations of leptin were similar to the relevant ones before treatment (SMD: 0.06, 95% CI: -0.09 to 0.20), with no heterogeneity among studies (I2: 0%, p = 0.875). After treatment, blood concentrations of adiponectin were similar to the relevant ones before treatment (SMD: -0.14, 95% CI: -0.34 to 0.05), with significant heterogeneity among studies (I2: 36.8%, p = 0.032). After treatment, blood concentrations of resistin were significantly lower as compared to the relevant ones before treatment (SMD: 0.50, 95% CI: 0.20 to 0.79), with significant heterogeneity among studies (I2: 61.4%, p < 0.001).
Conclusions
There is no evidence that treatment for psoriasis modifies leptin and adiponectin concentrations. In the opposite way, treatment intervention reduces resistin concentrations, a finding that is expected to be of clinical importance.
This article is protected by copyright. All rights reserved.
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A randomized, multi-national, non-inferiority, phase III trial to evaluate the safety and efficacy of BF-200 ALA gel versus MAL cream in the treatment of non-aggressive basal cell carcinoma with photodynamic therapy (PDT)
Abstract
Background
Basal cell carcinoma (BCC) represents the most common non-melanoma skin cancer worldwide affecting mainly adult, fair-skinned individuals. The WHO distinguishes aggressive and non-aggressive forms of which prototypical variants of the latter are primary nodular and superficial BCC.
Objectives
To demonstrate non-inferiority of BF-200 ALA (a nanoemulsion gel containing 5-aminolaevulinic acid) compared to MAL (a cream containing methyl-aminolevulinate) in the treatment of non-aggressive BCC with photodynamic therapy (PDT). Non-inferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF-200 ALA was no worse than that for MAL, within a statistical margin of Δ = -15%.
Patients/Methods
The study was a randomized, phase III trial performed in Germany and the UK with ongoing 5-year follow-up. Of 281 randomized patients, 138 were treated with BF-200 ALA, 143 with MAL. Patients received two PDT sessions one week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J/cm2). Results shown include clinical endpoints as well as patients' reassessment 12 months after the last PDT.
Results
Of the BF-200 ALA-treated patients, 93.4% were complete responders compared to 91.8% in the MAL group. The difference of means was 1.6 with a one-sided 97.5% CI of -6.5, establishing non-inferiority (p<0.0001). Results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.
Conclusions
Treatment of non-aggressive BCC with BF-200 ALA-PDT is highly effective and well tolerated with proven non-inferiority to MAL-PDT and demonstrates low recurrence rates after 1-year follow-up.
This article is protected by copyright. All rights reserved.
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Pilocarpine and Artificial Saliva for the Treatment of Xerostomia and Xerophthalmia of Sjögren's Syndrome: A double blind control trial
Abstract
Background
Sjögren's Syndrome (SS) is associated with xerostomia and xerophthalmia. Pilocarpine stimulates the secretion of saliva.
Objectives
Investigate and compare the efficacy of pilocarpine and artificial saliva as symptomatic treatments for xerostomia and xerophthalmia in patients with SS.
Patients and Methods
A double-blind, randomized, controlled study was performed. 72 patients with SS were assigned randomly to receive ten drops of pilocarpine (5 mg) or 10 drops of artificial saliva, orally, t.i.d.for 12 weeks. Patients were evaluated at baseline and periodically throughout the study by whole saliva and tear flow for global assessment of their dryness as well as for any adverse effects.
Results
Patients receiving pilocarpine had a statistically significant improvement in their salivary flow (p< 0.0001), lachrymal flow (p< 0.0001), and their subjective global assessment (p< 0.0001), compared with patients on artificial saliva. The most common side effects were sialorrhea and nausea.
Limitations
As the pilocarpine was in solution (drops), it was possible for the dosage to become inaccurate.
Conclusions
Pilocarpine is more effective than artificial saliva for enhancing salivary and lachrymal secretion in patients with SS. This is the first study comparing the efficacy of pilocarpine and artificial saliva as treatments for xerostomia and xerophthalmia in SS.
This article is protected by copyright. All rights reserved.
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The synergistic activities of the combination of TNF-α, IL-17A, and IFN-γ in epidermal keratinocytes
Abstract
Psoriasis vulgaris is a common chronic inflammatory skin disease characterized by abnormal epidermal hyperplasia and the infiltration of cells including neutrophils and T cells.1 Th1 and Th17 cells particularly infiltrate psoriatic lesions, and they are thought to play critical roles in the pathogenesis. Psoriatic keratinocytes are morphologically abnormal, and they are also involved in the cell infiltration.
Antibody agents that block key cytokines have been successfully used clinically for psoriasis.
This article is protected by copyright. All rights reserved.
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A Review of Clinical Trial Registry Use in Dermatology Systematic Reviews
Abstract
An inherent qualification of systematic reviews is that they attempt to collate all relevant empirical evidence. While properly conducted systematic reviews are considered the gold standard for determining health care policy and clinical decision making, they are vulnerable to publication bias1. Publication bias occurs when statistically nonsignificant data from unpublished literature are omitted from systematic reviews and meta-analyses2.
This article is protected by copyright. All rights reserved.
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Eccrine sweat glands associate with the human hair follicle within a defined compartment of dermal white adipose tissue
Summary
Background
Eccrine sweat glands (ESGs) are critical for thermoregulation and involved in wound healing. ESGs have traditionally been considered as separate skin appendages without connection to the pilosebaceous unit (PSU). However, recent preliminary evidence has encouraged the hypothesis that PSU and ESG are more interconnected than previously thought.
Objective
To reevaluate the morphology of human skin adnexa with an integrated 3D perspective in order to explore the possible interconnections that the PSU and the ESG may form.
Methods
A systematic 3D reconstruction method of skin sections, direct visualization of human scalp follicular unit transplant grafts and a scalp strip ex vivo were used to validate and further explore the hypothesis.
Results
We demonstrate that the coiled portion of most ESGs is morphologically integrated into the PSU of human scalp skin and forms a structural unit that is embedded into a specific, HF-associated region of dermal white adipose tissue (dWAT). This newly recognized unit is easily accessible and experimentally tractable by organ culture of follicular units and can be intravitally visualized.
Conclusions
We propose a model of functional human skin anatomy in which ESGs are closely associated with the PSU and the dWAT to form a common homeostatic tissue environment, which may best be encapsulated in the term adnexal skin unit (aSU). The challenge now is to dissect how each component of this superstructure of human skin functionally cooperates with and influences the other under physiological conditions, during regeneration/repair and in selected skin diseases.
This article is protected by copyright. All rights reserved.
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Role of TNFSF11 and Group 2 Innate Lymphoid Cells in Type 2 Inflammation in Chronic Rhinosinusitis with Nasal Polyps
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Noriko Ogasawara, Julie A. Poposki, Aiko I. Klingler, Bruce K. Tan, Kathryn E. Hulse, Whitney W. Stevens, Anju T. Peters, Leslie C. Grammer, Robert P. Schleimer, Kevin C. Welch, Stephanie S. Smith, David B. Conley, Joseph R. Raviv, Pejman Soroosh, Tetsuo Himi, Robert C. Kern, Atsushi Kato
http://ift.tt/2CdXihz
Recurrent Wheeze After Hospital Discharge Among Preschool Children Hospitalized With Acute Wheezing: 18-Months Follow-Up of A Multi-Center Study
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Patrada Thanee, Paskorn Sritipsukho, Orapan Poachanukoon, Araya Satdhabudha, Khlongtip Matchimmadamrong, Sasawan Chinratanapisit, Jitladda Deerojanawong, Pantipa Chatchatee, Narissara Suratannon
http://ift.tt/2EjK60x
IL33 Receptor Deficiency Leads To Steroid Resistant Asthma Due To TSLP-driven Increase In IL9+ILC2s And Mast Cells
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Mukesh Verma, Sucai Liu, Lidia Michalec, Anand Sripada, Magdalena M. Gorska, Rafeul Alam
http://ift.tt/2CfZ1mm
Table of Contents
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
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Group 2 innate lymphoid cells display ILC3-like functional plasticity in asthmatics and non-human primates
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Cameron H. Flayer, Moyar Qing Ge, Daniel G. Tompkins, Maya Juarez, Lisa Miller, Christopher M. Royer, Brian M. Morrissey, Nicholas J. Kenyon, Angela Haczku
http://ift.tt/2Cf8Dhg
Risk of Asthma Among Children from In-Utero Exposure to Traffic-Related Air Pollutants
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Christina D. Schwindt, Jun Wu, Ralph Delfino
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Meeting Announcement
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
http://ift.tt/2CeePpS
Identification of MEK2 and CBX7 as Top Steroid Resistant Genes in Airway ILC2s and Lymphocytes from Asthma
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Kapil Sirohi, Mukesh Verma, Lidia Michalec, Anand Sripada, Donald Rollins, James Good, Richard J. Martin, Magdalena M. Gorska, Rafeul Alam
http://ift.tt/2EnSMDe
TSLP and IL-33 Reciprocally Regulate Each Other’s Lung Protein Expression and Receptor Expression on ILC2 following Aeroallergen Challenge in Mice
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Shinji Toki, Baohua Zhou, Stokes Peebles
http://ift.tt/2CfoegP
COCKROACH SENSITIZATION AS DETERMINANT FACTOR IN ASTHMA CONTROL IN A TROPICAL URBAN YOUTH
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Julián E. Londoño Hernández, Rodrigo A. Gaviria, Jaime Ocampo, Victor Calvo, Ricardo Cardona
http://ift.tt/2EmkQqp
Effect of Food Allergy on Astma Control in children
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Sukruthi Jois, Betty Andy-Nweye, Alice N. Hackett, Opal J. Kamdar, Kylie N. Jungles, Ruchi S. Gupta, Mary C. Tobin, Mahboobeh Mahdavinia
http://ift.tt/2CgGarh
Overweight/Obesity as a risk factor for Severe Wheezing up to 5 years old
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
Author(s): Leticia Lambert, Luisa B. Savastano, Sephanie L. Vargas, Etienne L. Duim, Maria Celia C. Ciaccia, Vera E. Rullo
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Title Page
Publication date: February 2018
Source:Journal of Allergy and Clinical Immunology, Volume 141, Issue 2, Supplement
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A technique for teaching and photo-documentation of direct endoscopic rigid oesophagoscopy
Abstract
Direct oesophagoscopy is largely a diagnostic procedure performed for a variety of symptoms (e.g. unilateral otalgia or odonophagia) or as part of a panendoscopy to exclude a synchronous primary; therefore good visualisation of abnormal mucosa is essential. The current standard oesophagoscopy technique involves direct visualisation from approximately 25cm down a narrow, illuminated oesophagoscope limiting visualisation of abnormal mucosa. Usually performed by a single operator, the technique is difficult to teach, as the trainee is unable to visualise what the trainer is seeing endoluminally and visa versa.
This article is protected by copyright. All rights reserved.
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Differences in gene expression profile between vocal cord Leukoplakia and normal larynx mucosa by gene chip
Abstract
Background
Long non-coding RNAs (lncRNAs) play an important role in tumorigenesis. Vocal cord leukoplakia is a precancerous lesion in otolaryngological practice. Till now, the expression patterns and functions of lncRNAs in vocal cord leukoplakia have not been well understood. In this study, we used microarrays to investigate the aberrantly expressed lncRNAs and mRNAs in vocal cord leukoplakia and adjacent non-neoplastic tissues.
Methods
Gene Ontology and pathway analyses were performed to determine the significant function and pathways of the differentially expressed mRNAs. qRT-PCR was performed to further validate the expression of selected lncRNAs and mRNAs in vocal cord leukoplakia.
Results
Our study identified 170 differentially expressed lncRNAs and 99 differentially expressed mRNAs, including 142 up-regulated lncRNAs and 28 down-regulated lncRNAs, and 54 up-regulated mRNAs and 45 down-regulated mRNAs. Among these, XLOC_000605 and DLX6-AS1 were the most aberrantly expressed lncRNAs. Furthermore, we identified an antisense lncRNA (LOC100506801), an enhancer-like lncRNA (AK057351) and three long intergenetic noncoding RNAs including XLOC_008001, XLOC_011989 and XLOC_007341.
Conclusions
Our results revealed that many lncRNAs were differentially expressed between vocal cord leukoplakia tissues and normal tissue, suggesting that they may play a key role in vocal cord leukoplakia tumorigenesis.
http://ift.tt/2G3FXtZ
Important and specific role for basophils in acute allergic reactions
Abstract
IgE-mediated allergic reactions involve the activation of effector cells, predominantly through the high-affinity IgE receptor (FcεRI) on mast cells and basophils. Although the mast cell is considered the major effector cell during acute allergic reactions, more recent studies indicate a potentially important and specific role for basophils and their migration which occurs rapidly upon allergen challenge in humans undergoing anaphylaxis. We review the evidence for a role of basophils in contributing to clinical symptoms of anaphylaxis, and discuss the possibility that basophil trafficking during anaphylaxis might be a pathogenic (to target organs) or protective (preventing degranulation in circulation) response. Finally, we examine the potential role of basophils in asthma exacerbations. Understanding the factors that regulate basophil trafficking and activation might lead to new diagnostic and therapeutic strategies in anaphylaxis and asthma.
This article is protected by copyright. All rights reserved.
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Short chain fatty acids induce tissue plasminogen activator in airway epithelial cells via GPR41&43
Abstract
Background
Chronic rhinosinusitis (CRS) is a heterogeneous chronic inflammatory disease generally divided based on presence or absence of nasal polyps (NPs). One of the features of NPs is excessive fibrin deposition, which is associated with down regulation of tissue plasminogen activator (t-PA) in NPs. As t-PA is expressed in epithelial cells, and epithelium is readily accessible to topical therapies, identifying compounds that can mediate the induction of t-PA would be a potential new strategy for the treatment of NPs.
Objective
The objective of this study was to determine whether SCFAs can induce t-PA in airway epithelial cells via their known receptors GPR41 and GPR43.
Methods
We performed immunohistochemistry (IHC) to determine whether receptors for SCFAs, known as G protein coupled receptor 41/free fatty acid receptor 3 (GPR41/FFAR3) and GPR43/FFAR2, are expressed in nasal tissue. Primary normal human bronchial epithelial (NHBE) cells were stimulated with different concentrations of SCFAs to test induction of t-PA, which was analyzed by expression of mRNA and protein. Mediation of responses by SCFA receptors was evaluated by specific receptor gene silencing with siRNA.
Results
IHC study revealed that airway epithelial cells expressed GPR41 and GPR43. Acetic acid, propionic acid, butyric acid, and valeric acid significantly induced t-PA expression from 2-10 folds. The strongest inducer of t-PA from NHBE cells was propionic acid; cells stimulated with propionic acid released t-PA into the supernatant in its active form. Gene silencing of GPR41 and GPR43 revealed that induction of t-PA by SCFAs was dependent upon both GPR41 and GPR43.
Conclusions & Clinical Relevance
SCFAs were shown to induce airway epithelial cell expression of t-PA via GPR41 and GPR43. Topical delivery of potent compounds that activate these receptors may have value by reducing fibrin deposition and shrinking nasal polyp growth.
This article is protected by copyright. All rights reserved.
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Matters of the Heart: Story Ideas and an Expert Pitch for Heart Month and Valentine’s Day
Below are brief summaries of story ideas for February's Valentine's Day and American Heart Month
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Biomarker Predicts Success of Afib Treatment
Johns Hopkins researchers report successful use of heart imaging to predict the benefit or futility of catheter ablation, an increasingly popular way to treat atrial fibrillation, a common heart rhythm disorder.
http://ift.tt/2o1xRuC
Unusual AIP mutation and phenocopy in the family of a young patient with acromegalic gigantism
Summary
Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy.
Learning points:Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.
Unusual, previously not described AIP variant with loss of the stop codon.
Phenocopy may occur in families with a disease-causing germline mutation.
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Quantitative Analysis of Global Proteome in Bone Samples From Patients With Osteoporotic and Nonosteoporotic Fracture
Condition: Femoral Neck Fractures
Intervention: Procedure: total hip arthroplasty
Sponsor: Second Affiliated Hospital of Soochow University
Not yet recruiting
http://ift.tt/2nTSdXi
Intervention: Procedure: total hip arthroplasty
Sponsor: Second Affiliated Hospital of Soochow University
Not yet recruiting
http://ift.tt/2nTSdXi
Biospecimen Procurement for NIDCD Clinical Protocols
Conditions: Hearing Disorder; Oral Mucosal Disease; Pharyngeal Neoplasm; Head and Neck Neoplasms; Laryngeal Disease
Intervention:
Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD)
Recruiting
http://ift.tt/2o1kbzF
Intervention:
Sponsor: National Institute on Deafness and Other Communication Disorders (NIDCD)
Recruiting
http://ift.tt/2o1kbzF
OPPOSITE: Outcome Prediction Of Systemic Treatment in Esophagogastric Carcinoma
Conditions: Gastric Neoplasm; Gastroesophageal Junction Adenocarcinoma; Esophageal Adenocarcinoma; Gastric Adenocarcinoma; Esophageal Neoplasms
Intervention: Procedure: Biopsy
Sponsors: University Hospital Heidelberg; University Hospital Dresden; German Cancer Research Center
Not yet recruiting
http://ift.tt/2nU60Nr
Intervention: Procedure: Biopsy
Sponsors: University Hospital Heidelberg; University Hospital Dresden; German Cancer Research Center
Not yet recruiting
http://ift.tt/2nU60Nr
PET and MRI in Prognosis Prediction of NPC
Condition: Nasopharyngeal Carcinoma
Intervention: Device: integrated PET/MRI
Sponsor: Chang Gung Memorial Hospital
Recruiting
http://ift.tt/2o1k1Z5
Intervention: Device: integrated PET/MRI
Sponsor: Chang Gung Memorial Hospital
Recruiting
http://ift.tt/2o1k1Z5
Rapidly progressive neovascular glaucoma following coronary artery bypass graft surgery in a patient with type 1 diabetes mellitus: a case report
Proliferative diabetic retinopathy leading to vitreous hemorrhage, tractional retinal detachment, and neovascular glaucoma is a major cause of severe sight impairment in adults of working age worldwide. Neovas...
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Safe and effective intradermal influenza vaccine desensitization for delayed influenza vaccine allergy
Publication date: Available online 12 February 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Tsuzumi Kanaoka, Kazune Matsuoka, Marcus Shaker
http://ift.tt/2EArWXy
Efficacy of MAS063DP lotion vs 0.02% triamcinolone acetonide lotion in improving post-ablative fractional CO2 laser resurfacing wound healing: a split-face, triple-blinded, randomized, controlled trial
Abstract
Proven as effective acne scar treatment, ablative fractional carbon dioxide (AFCO2) laser requires post-laser wound healing care. MAS063DP is a multicomponent nonsteroidal anti-inflammatory moisturizer for effective post-laser treatment. This study compares the efficacy of MAS063DP and 0.02% triamcinolone acetonide (TA) lotion for post-laser wound healing and complications. A split-face, triple-blinded, clinical study was performed in 16 patients, aged 20–50 years, receiving AFCO2 on both sides of the face, with MAS063DP on one side and 0.02% TA on the other side for 7 days twice daily. Digital photography, hemoglobin, and melanin index at baseline were obtained immediately after laser treatment and then at days 3, 5, 7, and 30. Erythema, edema, crusting, adverse effects, and post-inflammatory hyperpigmentation (PIH) were followed every visit. Sixteen patients, mean age 38.6 (8.4) years, with moderate–severe atrophic scar and skin phototype III–IV completed the study. Clinical improvement of edema, erythema, crusting, and hyperpigmentation was observed from day 3 to day 30 (P < 0.001), with no statistically significant difference in both groups. There was also no statistical difference of hemoglobin, melanin index, and texture at days 3, 5, 7, and 30. Melanin index at day 30 was significantly less than baseline in both MAS063DP and 0.02% TA. With PIH in 50% of cases, both treatments demonstrated good safety profiles and no serious adverse reactions. MAS063DP could be an effective treatment for post-laser wound healing and complications, compatible to 0.02% TA.
http://ift.tt/2EjMDDU
The in-hospital burden of hidradenitis suppurativa in patients with inflammatory bowel disease: a decade nationwide analysis from 2004 to 2014
Abstract
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory disease that significantly affects the patient's quality of life. Multiple studies have shown a strong association between HS and inflammatory bowel disease (IBD). Our primary goal was to explore the in-hospital burden of HS on patients with IBD. Our secondary goal was to establish unique baseline characteristics and comorbidities of IBD patients with HS.
Methods
This was a retrospective cohort study using the National Inpatient Sample (NIS) database for the years 2004 through 2014. All patients with ICD-9 CM codes for any diagnosis of IBD and HS were included. The primary outcome was the medical and financial burden of HS on patients with IBD. Medical burden was measured by in-hospital morbidity and mortality, and financial burden was measured by resource utilization.
Results
A total of 3,079,332 admissions with IBD were recorded, of which 4369 had a concomitant diagnosis of HS. IBD-HS patients were significantly younger and mostly African-American females; they were more likely to be smokers, obese, and have diabetes mellitus, depression, and anemia. There was no mortality difference between the IBD-HS and IBD-only groups; nevertheless, there was a higher likelihood of developing sepsis in the IBD-HS cohort (4.9% vs. 2.6%; P < 0.001). Patients with IBD-HS had an increased hospital length of stay (5 vs. 4 days; P < 0.001) and higher total hospitalization costs ($13,272 vs. $12,237; P = 0.013).
Conclusions
This large-scale study strengthens the evidence that these two inflammatory conditions are truly associated and establishes their joint effect on overall morbidity, mortality, and resource utilization.
http://ift.tt/2EVFwCw
Recent advances and development in epidermal and dermal drug deposition enhancement technology
Abstract
Skin is the largest and easily accessible organ of the body. Increases in incidences of dermatological disorders, demand for drug targeting, and patient compliance have increased the popularity of topical drug delivery amongst the people. However, drug delivery across the skin is still a challenge for researchers because permeation of maximum drugs is hindered by the upper layer of the epidermis (stratum corneum). Several approaches like use of chemical permeation enhancers and physical methods such as sonophoresis, iontophoresis, electroporation, microneedles, etc., have been used to deliver the drugs topically. These methods of topical drug delivery have some limitations and drawbacks. Therefore new techniques based on nano drug delivery system such as ultradeformable liposomes, nanostructured lipid carriers, nanoemulsions, solid lipid nanoparticles, lipospheres, nanoparticles, and ethosomes have been exploited for enhancing epidermal and dermal drug deposition. Development of these nanosytems requires a good understanding of mechanism of drug permeation, physicochemical properties of drug and carriers, and technological advancements in methodology. Therefore, this article covers recent advances in epidermal and dermal drug deposition enhancement approaches, biopharmaceutical challenges with dermal drug delivery, issues in formulation development, and regulatory aspects of nanosystem. This review article also discusses the concern of topical drug delivery in immunization, gene delivery, and cosmeceuticals.
http://ift.tt/2EmJqDi
Innovative real CSF leak simulation model for rhinology training: human cadaveric design
Abstract
Objective
To study the feasibility of designing a human cadaveric simulation model of real CSF leak for rhinology training.
Method
The laboratory investigation took place at the surgical academic center of Prince Sultan Military Medical City between 2016 and 2017. Five heads of human cadaveric specimens were cannulated into the intradural space through two frontal bone holes. Fluorescein-dyed fluid was injected intracranialy, then endoscopic endonasal iatrogenic skull base defect was created with observation of fluid leak, followed by skull base reconstruction. The outcome measures included subjective assessment of integrity of the design, the ability of creating real CSF leak in multiple site of skull base and the possibility of watertight closure by various surgical techniques.
Results
The fluid filled the intradural space in all specimens without spontaneous leak from skull base or extra sinus areas. Successfully, we demonstrated fluid leak from all areas after iatrogenic defect in the cribriform plate, fovea ethmoidalis, planum sphenoidale sellar and clival regions. Watertight closure was achieved in all defects using different reconstruction techniques (overly, underlay and gasket seal closure).
Conclusion
The design is simulating the real patient with CSF leak. It has potential in the learning process of acquiring and maintaining the surgical skills of skull base reconstruction before direct involvement of the patient. This model needs further evaluation and competence measurement as training tools in rhinology training.
http://ift.tt/2EXlFmp
Follicular dendritic cell sarcoma of the duodenum: an extremely rare entity
Extranodal follicular dendritic cell sarcoma (FDCS) is a very rare tumour, only reported in case reports and case series. It poses diagnostic and management challenge both to the clinician and pathologist. We present such a rare case of duodenal FDCS in a 56-year-old woman who was recently managed in our institution. Repeated pre surgical biopsies were non-diagnostic and the final diagnosis was made only after surgical excision of the tumour and with the help of histopathological and immunohistochemical studies. The patient had a complete en block resection of the tumour and was discharged home well 5 days postsurgery. To the best of our knowledge, this is the first case of FDCS reported arising from the duodenum.
http://ift.tt/2EkzB93
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