Cardiac abnormalities due to multisystem inflammatory syndrome temporally associated with Covid-19 among children: A systematic review and meta-analysis

Background: Cardiac defects due to multisystem inflammatory syndrome in children (MIS-C) have been abundantly reported leading high morbidity among children affected by Covid-19. We aimed to systematically assess the incidence of such cardiac abnormalities due to MIS-C in children suffering Covid-19. Methods: The manuscript databases including Medline, Web of knowledge, Google scholar, Scopus, and Cochrane were deeply searched by the two blinded investigators for all eligible studies based on the relevant keywords. The risk of bias for each study was assessed according to QUADAS-2 tool. Statistical analysis was performed using the Comprehensive Meta Analysis (CMA) software. Results: In final, 21 articles (including 916 children) were eligible for the final analysis that all yielded good quality and none of the citation was determined to have high risk of bias. Considering studies focusing different cardiac abnormalities related to MIS-C yielded a pooled prevalence of 38.0 for significant left ventricular dysfunction, 20.0 for coronary aneurism or dilatation, 28.1 for ECG abnormalities or cardiac arrhythmias, 33.3 for raised serum troponin level and 43.6 for raised proBNP/BNP level. Conclusion: Although cardiac abnormalities among children suffering Covid-19 are uncommon, in the context of the MIS-C can be common and therefore potentially serious and life threatening. © 202

Endophthalmitis caused by Acinetobacter spp. as the presenting manifestation of diabetes mellitus

Purpose We describe a patient with endogenous endophthalmitis caused by Acinetobacter spp. as the first clinical presentation of diabetes mellitus. Method A 48-year-old otherwise healthy woman was referred with signs and symptoms of acute endophthalmitis in the left eye. Systemic work-up, vitreous tap, and intravitreal antibiotic injection were performed followed by pars plana vitrectomy. Results The laboratory tests confirmed the diagnosis of diabetes mellitus. Vitreous culture was positive for Acinetobacter spp., and the organism was sensitive to colistin. One month after surgery, vision was no light perception, and the eye was phthisical. Conclusion Diagnostic work-up should be performed even in otherwise healthy patients with endogenous endophthalmitis. © 2016 Iranian Society of Ophthalmolog

SNOT-22 in a Control Population

AIM: To assess SNOT-22 and its subscales in a non-rhinosinusitis UK-wide population.  METHODOLOGY/PRINCIPLE: This analysis uses data from the 'Chronic Rhinosinusitis Epidemiology Study' (CRES) which recruited from 30 centres across the UK, and the Socioeconomic Cost of ChrOnic Rhinosinusitis study' (SocCoR); 250 volunteers without CRS were recruited as part of these studies. Study-specific questionnaires including demographics, socioeconomic factors and past medical history as well as SNOT-22 and SF-36 were distributed. The control (non-CRS) population had no self-reported nasal problems in the past, no chronic conditions undergoing active treatment and no hospital admissions in the preceding 12 months.  RESULTS: The mean SNOT-22 total score overall was 12.0. The mean was 10.2 for males with a median of 6.5, and a mean of 13.2 for females with a median of 9. Females scored significantly more highly than males on the sleep/fatigue and facial domains.  CONCLUSIONS: Our data demonstrate differences in SNOT-22 amongst males and females. These data can be used in future studies for comparison with different disease populations with rhinosinusitis. This article is protected by copyright. All rights reserved

Current use of baseline medical treatment in chronic rhinosinusitis: Data from the National Chronic Rhinosinusitis Epidemiology Study (CRES)

Objectives: According to clinical and comissioning guidelines for chronic rhinosinusitis (CRS), patients being referred to secondary care should have failed primary medical treatment with nasal douching (ND) and intranasal corticosteroids (INCS). The study objectives were to identify the rate of specific medical therapy in CRS patients and establish any differences in medication use, for both CRS and associated medical conditions, between CRS phenotypes.  Design and setting: Case-control study in a secondary care setting.  Methods: Participant-reported study-specific questionnaire capturing free text data on current medication use at the time of study entry. Qualitative interviews with 21 participants also explored their experience of CRS and its management.  Particpants: Patients with both without (CRSsNPs) and with polyps (CRSwNPs). Main outcome measuresReported use of CRS-related and non-related medications.ResultsWithin a total of 1243 CRS participants, current INCS usage was low (18% in CRSwNPs, 12% in CRSsNPs); ND was being performed by only 1% of all participants. Bronchodilators and inhaled corticosteroids use was significantly higher in CRSwNPs participants (p < 0.0001). Antidepressants use was significantly higher in CRSsNPs (14% versus 7%, p < 0.0002). There were no significant regional variations in rates of INCS use, nor any significant influence of social deprivation.  Conclusions: The current use of baseline medical therapy in CRS appears to be very low, representing a combination of poor patient compliance, possible ineffectiveness of treatment and a lack of familiarity with current guidelines amongst general practitioners and some ENT specialists. Work is needed to disseminate guidelines to all practitioners involved and reduce unnecessary burden on existing healthcare resources for this common condition by ensuring timely referral and definitive management

High-performance liquid chromatography–tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites

Applications of tandem mass spectrometry (MS/MS) techniques coupled with high-performance liquid chromatography (HPLC) in the identification and determination of phase I and phase II drug metabolites are reviewed with an emphasis on recent papers published predominantly within the last 6 years (2002–2007) reporting the employment of atmospheric pressure ionization techniques as the most promising approach for a sensitive detection, positive identification and quantitation of metabolites in complex biological matrices. This review is devoted to in vitro and in vivo drug biotransformation in humans and animals. The first step preceding an HPLC-MS bioanalysis consists in the choice of suitable sample preparation procedures (biomatrix sampling, homogenization, internal standard addition, deproteination, centrifugation, extraction). The subsequent step is the right optimization of chromatographic conditions providing the required separation selectivity, analysis time and also good compatibility with the MS detection. This is usually not accessible without the employment of the parent drug and synthesized or isolated chemical standards of expected phase I and sometimes also phase II metabolites. The incorporation of additional detectors (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and MS instruments can result in valuable analytical information supplementing MS results. The relation among the structural changes caused by metabolic reactions and corresponding shifts in the retention behavior in reversed-phase systems is discussed as supporting information for identification of the metabolite. The first and basic step in the interpretation of mass spectra is always the molecular weight (MW) determination based on the presence of protonated molecules [M+H]+ and sometimes adducts with ammonium or alkali-metal ions, observed in the positive-ion full-scan mass spectra. The MW determination can be confirmed by the [M-H]- ion for metabolites providing a signal in negative-ion mass spectra. MS/MS is a worthy tool for further structural characterization because of the occurrence of characteristic fragment ions, either MSn analysis for studying the fragmentation patterns using trap-based analyzers or high mass accuracy measurements for elemental composition determination using time of flight based or Fourier transform mass analyzers. The correlation between typical functional groups found in phase I and phase II drug metabolites and corresponding neutral losses is generalized and illustrated for selected examples. The choice of a suitable ionization technique and polarity mode in relation to the metabolite structure is discussed as well

Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological materials covalently or engaging in redox-cycling reactions leading to the formation of other toxicants. Alternatively, they may result from the formation of a major metabolite with systemic exposure and adverse pharmacological activity. To avert such problems, biotransformation studies are becoming increasingly important in guiding the refinement of a lead series during drug discovery and in characterizing lead candidates prior to clinical evaluation. This article provides an overview of the methods that are used to uncover metabolism-related liabilities in a pre-clinical setting and offers suggestions for reducing such liabilities via the modification of structural features that are used commonly in drug-like molecules

Advances in structure elucidation of small molecules using mass spectrometry

The structural elucidation of small molecules using mass spectrometry plays an important role in modern life sciences and bioanalytical approaches. This review covers different soft and hard ionization techniques and figures of merit for modern mass spectrometers, such as mass resolving power, mass accuracy, isotopic abundance accuracy, accurate mass multiple-stage MS(n) capability, as well as hybrid mass spectrometric and orthogonal chromatographic approaches. The latter part discusses mass spectral data handling strategies, which includes background and noise subtraction, adduct formation and detection, charge state determination, accurate mass measurements, elemental composition determinations, and complex data-dependent setups with ion maps and ion trees. The importance of mass spectral library search algorithms for tandem mass spectra and multiple-stage MS(n) mass spectra as well as mass spectral tree libraries that combine multiple-stage mass spectra are outlined. The successive chapter discusses mass spectral fragmentation pathways, biotransformation reactions and drug metabolism studies, the mass spectral simulation and generation of in silico mass spectra, expert systems for mass spectral interpretation, and the use of computational chemistry to explain gas-phase phenomena. A single chapter discusses data handling for hyphenated approaches including mass spectral deconvolution for clean mass spectra, cheminformatics approaches and structure retention relationships, and retention index predictions for gas and liquid chromatography. The last section reviews the current state of electronic data sharing of mass spectra and discusses the importance of software development for the advancement of structure elucidation of small molecules