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A stability-indicating UV spectroscopic and high-performance liquid chromatography (RP-HPLC) method is developed for the quantification ofPioglitazone, Glimepiride & Metformin Hydrochloride drug substances. UV spectroscopic method was developed and validated, the wavelength selected for simultaneous estimation were 226nm for pioglitazone, 229nm for glimepiride and 232nm for metformin hydrochloride. The isosbestic point found for the analysis was 229nm. Selected mobile phase was a combination of methanol and water with a ratio of 70% Methanol and 30 % HPLC water with the flow rate of 0.85ml/min. The analyte was analysed on the C18 HPLC column having the pore size of 5 microns at room temperature. The method is validated according to ICH guidelines, the retention time of about 4.0min for metformin, 5.5min for Pioglitazone and 6.8min for Glimepiride was observed. The linearity range with regression co-efficient for Pioglitazone, Glimepiride & Metformin Hydrochloride is 3-15 ?g/mL,0.4-1.2 ?g/mL and 100-500 ?g/mL and 0.9998, 0.9991, 0.9991 respectively. Keywords: Glimepiride, Pioglitazone, Ruggedness

Traditional medicine and medicinal plants, as well as their study of modern chemical principles, may lead to the development of newer, less expensive medications. Ginkgo Biloba is well-known for curing a variety of ailments and is utilized in a variety of traditional medicinal formulations. Scientists and researchers from all over the world have spent decades studying the chemical composition of the entire Ginkgo Biloba plant, as well as its biological and pharmacological functions. These investigations established Ginkgo Biloba's medicinal potential in modern medicine and as a prospective drug discovery candidate. The current paper provides an overview of Ginkgo Bilobaethnobotany, phytochemistry, pharmacology, and toxicity. Keywords: Medicinal plants, Ginkgo Biloba, Ethnobotany, Phytochemistry, Pharmacology

Data are urgently needed on the real-world effectiveness of the currently administered COVID-19 vaccines. This case–control study evaluated the short-term effectiveness of currently administered vaccines in preventing confirmed SARS-CoV-2 infection among veterans receiving care in the U.S. Department of Veterans Affairs health care system., Visual Abstract. SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population. Data are urgently needed on the real-world effectiveness of the currently administered COVID-19 vaccines. This case–control study evaluated the short-term effectiveness of currently administered vaccines in preventing confirmed SARS-CoV-2 infection among veterans receiving care in the U.S. Department of Veterans Affairs health care system. Visual Abstract. SARS-CoV-2 Vaccine Effectiveness in a High-Risk National Population. Data are urgently needed on the real-world effectiveness of the currently administered COVID-19 vaccines. This case–control study evaluated the short-term effectiveness of currently administered vaccines in preventing confirmed SARS-CoV-2 infection among veterans receiving care in the U.S. Department of Veterans Affairs health care system., Background: With the emergency use authorization of multiple vaccines against SARS-CoV-2 infection, data are urgently needed to determine their effectiveness in a real-world setting. Objective: To evaluate the short-term effectiveness of vaccines in preventing SARS-CoV-2 infection. Design: Test-negative case–control study using conditional logistic regression. Setting: U.S. Department of Veterans Affairs health care system. Participants: All veterans who had testing for SARS-CoV-2 infection between 15 December 2020 and 4 March 2021 and no confirmed infection before 15 December 2020. Intervention: SARS-CoV-2 vaccination with either the BNT-162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine as part of routine clinical care. Measurements: Effectiveness of vaccination against confirmed SARS-CoV-2 infection. Results: Among 54 360 persons who tested positive and 54 360 propensity score–matched control participants, the median age was 61 years, 83.6% were male, and 62% were White. Median body mass index was 31 kg/m2 among those who tested positive and 30 kg/m2 among those who tested negative. Among those who tested positive, 9800 (18.0%) had been vaccinated; among those who tested negative, 17 825 (32.8%) had been vaccinated. Overall vaccine effectiveness 7 or more days after the second dose was 97.1% (95% CI, 96.6% to 97.5%). Effectiveness was 96.2% (CI, 95.5% to 96.9%) for the Pfizer–BioNTech BNT-162b2 vaccine and 98.2% (CI, 97.5% to 98.6%) for the Moderna mRNA-1273 vaccine. Effectiveness remained above 95% regardless of age group, sex, race, or presence of comorbidities. Limitations: Predominantly male population; lack of data on disease severity, mortality, and effectiveness by SARS-CoV-2 variants of concern; and short-term follow-up. Conclusion: Currently used vaccines against SARS-CoV-2 infection are highly effective in preventing confirmed infection in a high-risk population in a real-world setting. Primary Funding Source: None.

Fatema S Shaikh,1 Nahier Aldhafferi,1 Areej Buker,1 Abdullah Alqahtani,1 Subhodeep Dey,2 Saema Abdulhamid,1 Dalal Ali Mahaii AlBuhairi,1 Raha Saud Abdulaziz Alkabour,1 Waad Sami O Atiyah,1 Sara Bachar Chrouf,1 Abdussalam Alshehri,3 Sunday Olusanya Olatunji,1 Abdullah M Almuhaideb,1 Mohammed S Alshahrani,4 Yousof AlMunsour,1 Vahitha B Abdul-Salam5 1College of Computer Science and Information Technology, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia; 2Indian Institute of Management – Calcutta, Kolkata, India; 3Prince Mohammed bin Abdulaziz Hospital, Riyadh, Saudi Arabia; 4College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Eastern Province, Saudi Arabia; 5Centre for Cardiovascular Medicine and Device Innovation, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UKCorrespondence: Fatema S Shaikh Tel +966-5591660024Email fsshaikh@iau.edu.saPurpose: The first novel coronavirus disease-19 (COVID-19) case in the Kingdom of Saudi Arabia (KSA) was reported in Qatif in March 2020 with continual increase in infection and mortality rates since then. In this study, we aim to determine risk factors which effect severity and mortality rates in a cohort of hospitalized COVID-19 patients in KSA.Method: We reviewed medical records of hospitalized patients with confirmed COVID-19 positive results via reverse-transcriptase-polymerase-chain-reaction (RT-PCR) tests at Prince Mohammed Bin Abdulaziz Hospital, Riyadh between May and August 2020. Data were obtained for patient’s demography, body mass index (BMI), and comorbidities. Additional data on patients that required intensive care unit (ICU) admission and clinical outcomes were recorded and analyzed with Python Pandas.Results: A total of 565 COVID-19 positive patients were inducted in the study out of which, 63 (11.1%) patients died while 101 (17.9%) patients required ICU admission. Disease incidences were significantly higher in males and non-Saudi nationals. Patients with cardiovascular, respiratory, and renal diseases displayed significantly higher association with ICU admissions (p< 0.001) while mortality rates were significantly higher in COVID-19 patients with cardiovascular, respiratory, renal and neurological diseases. Univariate cox proportional hazards regression model showed that COVID-19 positive patients requiring ICU admission [Hazard’s ratio, HR=4.2 95% confidence interval, CI 2.5– 7.2); p< 0.001] with preexisting cardiovascular [HR=4.1 (CI 2.5– 6.7); p< 0.001] or respiratory [HR=4.0 (CI 2.0– 8.1); p=0.010] diseases were at significantly higher risk for mortality among the positive patients. There were no significant differences in mortality rates or ICU admissions among males and females, and across different age groups, BMIs and nationalities. Hospitalized patients with cardiovascular comorbidity had the highest risk of death (HR=2.9, CI 1.7– 5.0; p=0.020).Conclusion: Independent risk factors for critical outcomes among COVID-19 in KSA include cardiovascular, respiratory and renal comorbidities.Keywords: COVID-19, SARS-CoV-2, mortality rate, comorbidities, risk factors, KSA

SARS-CoV-2 has caused a global pandemic of an acute respiratory illness known as COVID-19. Patients with solid organ transplants receiving chronic immunosuppressive therapy are at risk of severe disease caused by opportunistic pathogens, including cytomegalovirus (CMV). We present the case of a renal transplant recipient presenting with hypoxic respiratory failure because of severe COVID-19, whose course was complicated by ganciclovir-resistant CMV pneumonitis.

Recurrent attacks of rheumatic fever can lead to mitral stenosis. In a country like India mitral stenosis can develop in the first decade of life. Our patient presented with recurrent mitral stenosis at twelve years of age. He had undergone balloon mitral valvotomy at the age of seven. However this time he developed anterior mitral valve leaflet tear after balloon mitral valvotomy and had to be taken for mitral valve repair. Due to severe fibrosis of mitral valve the patient underwent mitral valve replacement. He was started on warfarin and dose titrated according to PT / INR. Patient was discharged but has to be on lifelong anticoagulation from the age of twelve.

Background: Human Papillomavirus (HPV) is responsible for substantial morbidity and mortality worldwide. We predicted immunogenic promiscuous monovalent and polyvalent T-cell epitopes from the polyprotein of the Human Papillomavirus (HPV) using a range of bioinformatics tools and servers. Methods: We used immunoinformatics and reverse vaccinology-based approaches to design prophylactic peptides by antigenicity analysis, T-cell epitopes prediction, proteasomal and conservancy evaluation, host-pathogen protein interactions, and in silico binding affinity analysis. Results: We found two early proteins (E2 and E6) and two late proteins (L1 and L2) of HPV as potential vaccine candidates. Of these proteins (E2, E6, L1 & L2), 2-epitopes of each candidate protein for multiple alleles of MHC class I and II bearing significant binding affinity (>-6.0 kcal/mole). These potential epitopes for CD4+ and CD8+ T-cells were also linked to design polyvalent construct using GPGPG linkers. Cholera toxin B and mycobacterial heparin-binding hemagglutinin adjuvant with a molecular weight of 12.5 and 18.5 kDa were used for epitopes of CD4+ and CD8+ T-cells respectively. The molecular docking indicated the optimum binding affinity of HPV peptides with MHC molecules. This interaction showed that our predicted vaccine candidates are suitable to trigger the host immune system to prevent HPV infections. Conclusion: The predicted conserved T-cell epitopes would contribute to the imminent design of HPV vaccine candidates, which will be able to induce a broad range of immune-responses in a heterogeneous HLA population.

Coughing is a common symptom of several respiratory diseases. The sound and type of cough are useful features to consider when diagnosing a disease. Respiratory infections pose a significant risk to human lives worldwide as well as a significant economic downturn, particularly in countries with limited therapeutic resources. In this study we reviewed the latest proposed technologies that were used to control the impact of respiratory diseases. Artificial Intelligence (AI) is a promising technology that aids in data analysis and prediction of results, thereby ensuring people’s well-being. We conveyed that the cough symptom can be reliably used by AI algorithms to detect and diagnose different types of known diseases including pneumonia, pulmonary edema, asthma, tuberculosis (TB), COVID19, pertussis, and other respiratory diseases. We also identified different techniques that produced the best results for diagnosing respiratory disease using cough samples. This study presents the most recent challenges, solutions, and opportunities in respiratory disease detection and diagnosis, allowing practitioners and researchers to develop better techniques.

Background: CIN is an important cause of morbidity and mortality post cardiac procedures. Renal derangement and diabetes being the most important risk factors. Multifactorial causation of the disorder led us to study the risk factors associated with CIN. Methods: All patients who underwent cardiac procedures between March 2019 and March 2020 were screened for CIN and included in the study. Out of the 3192 patients screened 99 patients were diagnosed with CIN. Parameters such as diabetes mellitus, hypertension, CKD, anemia, duration of hospital stay, cardiogenic shock, number of stents, amount and type of contrast, Ejection Fraction, creatinine clearance before and after the procedure, concomitant nephrotoxic drugs were also recorded. Results: Ninety-nine patients developed CIN amounting to 3% of the total procedures, 11% expired, 18% required dialysis, average creatinine clearance before the procedure was 53.15 ml/min/1.73 m2 and post procedure it was 29.16 ml/min/1.73 m2, 51.5% of cases had creatinine clearance prior to procedure

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality. The tumor carries poor prognosis with curative therapeutic options limited to surgical resection, tumor ablation, and liver transplantation. Rarely, there is spontaneous regression of the tumor. We describe the case of a 74-year-old male with cirrhosis from non-alcoholic steatohepatitis who developed advanced HCC that was associated with tumor invasion of the portal vein and marked elevation of serum alfa-fetoprotein level. The patient received no cancer-specific therapy. However, 1 year after the initial diagnosis, he was noted to have complete regression of the tumor. In this report, we discuss possible mechanisms of spontaneous tumor regression and its therapeutic implications.

Aim: Single coronary artery is a rare anomaly. Patients may present with syncope, angina or rarely sudden cardiac death. Presentation of Case: Patient presented with dyspnea on exertion for one year. On 2D Echo patient had small restrictive VSD. On coronary angiography single coronary artery from right cusp was seen. On CT angiography anomalous origin was confirmed. There was no malignant course of coronary artery. Discussion: Anomalous origin of coronary arteries are rare cardiac anomalies. It can present as syncope, angina, or sudden cardiac death especially in patients with malignant course of coronary artery passing between aorta and pulmonary artery. Hence CT coronary angiography is useful to rule out the malignant course. In our patient, there was no malignant course hence managed conservatively. Conclusion: Anomalous origin of coronary artery is a rare anomaly and requires tailored treatment according to type and course of artery.

Treating HCV infection reduces overall mortality and reduces the risk of multiple extrahepatic complications. Whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications is unknown.We identified HCV-positive individuals treated for HCV, and propensity score-matched them to HCV-positive/untreated and HCV-uninfected individuals in ERCHIVES between 2002-2016. We extracted cause of death data from the National Center for Health Statistics' National Death Index. Viral hepatitis-associated liver-related mortality rates among treated and untreated HCV-infected persons were calculated by treatment and attainment of sustained virologic response (SVR).Among 50,674 HCV-positive/treated (Group A), 31,749 HCV-positive/untreated (Group B) and 73,526 HCV-uninfected persons (Group C), 8.6% in Group A, 35.0% in Group B, and 14.3% in Group C died. Among those who died, viral hepatitis-associated liver-related mortality rates per 100 patient-years (95% CI) were: 0.28 (0.27-0.30) for Group A; 1.44 (1.38-1.49) for Group B; and 0.06 (0.05-0.06) for Group C; (p0.0001 for both comparisons). Among HCV-positive/treated persons, rates were 0.06 (0.05-0.06) for those with SVR vs. 0.78 (0.74-0.83) for those without SVR. In competing risks Cox proportional hazards analysis, treatment with all-oral DAA regimens (adjusted hazard ratio 0.11; 95% CI 0.09-0.14) and SVR (adjusted hazard ratio 0.10; 95% CI 0.08-0.11) were associated with reduced hazards of liver-related mortality.Treatment for HCV is associated with a significant reduction in viral hepatitis-associated liver-related mortality, which is particularly pronounced in those treated with DAA regimens and those who attain SVR. This may account for a significant proportion of the reduction in all-cause mortality reported in previous studies.Treating hepatitis C virus (HCV) infection is known to reduce overall mortality. However, whether the reduction in mortality is primarily due to a reduction in liver-related causes or extrahepatic complications was previously unknown. Herein, we show that while treating HCV with direct-acting antiviral regimens has numerous extrahepatic benefits, a significant benefit can be attributed specifically to the reduction in liver-related mortality.

Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead molecules 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.

Skin pigmentation is a highly heterogeneous trait with diverse consequences worldwide. SLC24A5, encoding a potent K(+)-dependent Na(+)/Ca(2+) exchanger, is among the known color-coding genes that participate in melanogenesis by maintaining pH in melanosomes. Deficient SLC24A5 activity results in oculocutaneous albinism (OCA) type 6 in humans. In this study, by utilizing a exome sequencing (ES) approach, we identified two new variants [p. (Gly110Arg) and p. (IIe189Ilefs*1)] of SLC24A5 cosegregating with the OCA phenotype, including nystagmus, strabismus, foveal hypoplasia, albinotic fundus and vision impairment, in three large consanguineous Pakistani families. Both of these variants failed to rescue the pigmentation in zebrafish slc24a5 morphants, confirming the pathogenic effects of the variants. We also phenotypically characterized a commercially available zebrafish mutant line (slc24a5(ko)) that harbors a nonsense (p.Tyr208*) allele of slc24a5. Similar to morphants, homozygous slc24a5(ko) mutants had significantly reduced melanin content and pigmentation. Next, we used these slc24a5(ko) zebrafish mutants to test the efficacy of nitisinone, a compound known to increase ocular and fur pigmentation in OCA1 (TYR)-mutant mice. Treatment of slc24a5(ko) mutant zebrafish embryos with varying doses of nitisinone did not improve melanin production and pigmentation, suggesting that treatment with nitisinone is unlikely to be therapeutic in OCA6 patients.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in diabetics. However, it is not the sole cause of chronic liver disease in diabetics. We present a case of an 18-year-old male with poorly controlled type I diabetes mellitus who presented for evaluation of asymptomatic elevated liver chemistries. An extensive autoimmune, metabolic, and infectious workup was unrevealing. Liver biopsy was consistent with glycogenic hepatopathy without evidence of steatosis or fibrosis. Increased glycemic control led to his liver enzymes trending down. In conclusion, glycogenic hepatopathy should be considered in poorly controlled type 1 diabetics with elevated liver chemistries.

Retroperitoneal tumour which can be benign or malignant is a rare entity (of which vascular neoplasms are extremely rare) with late clinical presentation, most often diagnosed in advanced stage of the disease. The complex anatomical location in the retroperitoneum, its inaccessibility and close relation to important structures in the retroperitoneal space pose a greater challenge in the diagnosis and the management of the disease. Here we are presenting a case of retroperitoneal tumour which presented with lump in abdomen since 10 years. Biopsy of the lump was suggestive of benign lesion. Complete surgical excision of the tumour was done and on final histopathology was suggestive of benign vascular neoplasm consistent with venous/cavernous hemangioma. Regular follow-up is uneventful.

The constant use of wrinkle-resistant cellulose fabrics in professional and everyday life can negatively affect the health state. This is because formaldehyde vapours, which contribute to allergies, persistent coughing, and irritation of the eyes, nose, and throat, sleep disturbances, headaches, etc., pose a greater danger. In this study an attempt was made to achieve fabric stabilization from wrinkle resistant by formation ionic bonds of as replacement covalent bonds. And this is the main study purpose. Industrially Desized and Bleached 100 % pure cotton fabric with the weight of 110 g/m2, and the chemicals were used. Preparation of cationic glycerine, carboxymethylation of bleached fabric and application of antimicrobial finishes on the ionic cross-linked fabric was provided. Measurements were taken to determine of wrinkle recovery angle (WRA), of absorbency, of whiteness index, of flexural rigidity, of abrasion, of tensile strength. Wrinkle recovery angle was measured by standard method of AATCC 66 (option 2). AATCC Test Method 79-2000 was used to test the absorbency of fabric. The CIE whiteness index was determined using an Xrite Colour Eye 7000A spectrophotometer. Flexural Rigidity was measured through a testing cantilever method ASTM D-1388. Fabric abrasion was checked according to standard method for abrasion resistance of textile fabric ASTM 4966 on Martindale Abrasion Device M235. Mechanical strength of the fabric was measured under the standard method of ASTM D-5034. With the ionic cross-linking, the dry WRA was achieved an optimum of 118º and wet WRA up to 128º with increased fabric strength and whiteness. In addition to ionic cross-linking fabric was treated with Nano silver. Based on the results it was concluded that the fabric can be optimized first with ionic cross-link method and then it can be treated with the antimicrobial making the fabric cleaner and hygienic. This fabric treatment provides the necessary characteristics and is safe for the health of the people who use it.

Tinospora cordifolia (Willd.) Miers (TC), family Menispermaceae is a well-known traditional herb reported in traditional Indian literature for the treatment of various disorders such as diabetes and cardiovascular diseases. Berberine, the chief active constituent of TC is reported to possess anti-diabetic potential along with other isoquinoline alkaloids. TC and its active constituent berberine both have been reported to be potent CYP2C9 inhibitor, thereby raising herb drug interaction (HDI) potential on co-administration with drugs metabolized through the CYP pathway. The present study evaluated the pharmacokinetic HDI of TC hydroalcoholic extract with Glimepiride (GP) after oral co-administration in Wistar rats using in vivo pharmacokinetic and in silico studies. After oral co-administration of TC extract (100 mg/kg) with GP (20 mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, Tmax, AUC, Vd, CL, and MRT0-t were calculated using Win Nonlin software. Also in silico molecular docking study using CYP2C9 (PDB ID: 1R90) as target protein and phytoconstituents (isoquinoline alkaloids) of TC as ligands were carried out using Auto Dock Vina 1.1.2 to determine their CYP2C9 interaction potential. The PK interactions studies demonstrated an increase in the systemic levels of GP. A significant increase in Cmax, AUC0-t and MRT0-t of GP (p

The discovery of a series of thiophenephenylsulfonamides as positive allosteric modulators (PAM) of α7 nicotinic acetylcholine receptor (α7 nAChR) is described. Optimization of this series led to identification of compound 28, a novel PAM of α7 nicotinic acetylcholine receptor (α7 nAChR). Compound 28 showed good in vitro potency, with pharmacokinetic profile across species with excellent brain penetration and residence time. Compound 28 robustly reversed the cognitive deficits in episodic/working memory in both time-delay and scopolamine-induced amnesia paradigms in the novel object and social recognition tasks, at very low dose levels. Additionally, compound 28 has shown excellent safety profile in phase 1 clinical trials and is being evaluated for efficacy and safety as monotherapy in patients with mild to moderate Alzheimer's disease.

The present study was designed to check the molecular detection of Anaplasma marginale and Theileria annulata in blood samples of horses and donkeys collected from Dera Ghazi Khan District in Punjab and to document their phylogenetic origin and their association with studied epidemiological factors (sex and age) and complete blood count parameters, if any. A total of 195 blood samples were collected from apparently healthy horses (N = 141) and donkeys (N = 54). A. marginale DNA was detected by PCR in 4.9% (7/141) horse and in 9.2% (5/54) of donkey blood samples. Prevalence of T. annulata was 5.6% (8/141) and 11.1% (6/54) in horse and donkey samples, respectively. While 1.4% (N = 2) horses and 3.7% (N = 2) donkeys were found co-infected with both parasites. Representative amplicon for both parasites was confirmed by DNA sequenced and partial DNA sequence of the major surface protein–1b encoding gene of A. marginale and cytochrome b gene from T. annulata were submitted to the GenBank database under the accession number MK792344-MK792348. Epidemiological data analysis revealed that female horses were more prone to A. marginale (P = 0.02) while female donkeys were more susceptible to A. marginale (P

Losartan potassium (LOS), used in the treatment of hypertension, is metabolized primarily by cytochrome P450. This study investigates the effect of quercetin (QU), a CYP3A4 inducer, on the pharmacokinetics of LOS in rats. A rapid, sensitive high-performance thin-layer chromatography (HPTLC) method was developed and validated for the bioanalysis of losartan using olmesartan as internal standard (IS). The salting-out assisted liquid—liquid extraction (SALLE) employing acetonitrile and MgCl2 gave high recovery of LOS (>90%). HPTLC separation, achieved on silica gel 60 F254 plates employing toluene—ethyl acetate—acetone—formic acid (4:4:1:0.5 V/V) as the mobile phase, with densitometric analysis at 240 nm, gave good linearity (50–1200 ng mL-1) with high intra-day and i nter-day precision. LOS in plasma samples was stable when stored under different stability conditions. The pharmacokinetics of LOS was found to be significantly altered when co-administered with QU: C max = 809.8 ± 4.1 at 40 min (t max) to C max = 1124.8 ± 86.6 ng mL-1 at 120 min (t max). This study indicates the chances of herb—drug interaction when LOS is co-administered with QU, leading to its increased bioavailability, potentiating its side effect/toxic manifestation. As QU is abundantly present in herbs and dietary food, patients of LOS therapy need to be cautious while concurrently consuming herbal preparations containing QU. This study also demonstrates the utility of HPTLC as an effective tool for pharmacokinetics study for the estimation of herb—drug interactions.

Targeting nuclear receptor RORγ is recognized to be beneficial in multiple autoimmune disorders. We disclosed new indole analogues as potent RORγ inverse agonists. RO-2 as one of the potent and orally bioavailable compounds was evaluated in various models of autoimmune disorder. It showed potent suppression of downstream markers of RORγt activity in murine and human primary cells, ex vivo PD assay and in multiple animal models of autoimmune diseases. The results indicate the potential of these indole analogues as orally bioavailable small molecule inverse agonists of RORγt, efficacious in various Th17 driven models of autoimmune disorders.

INTRODUCTION Although opioids are widely used for pain management in acute pancreatitis, the impact of opioid use disorder (OUD) on outcomes in patients with acute pancreatitis remains unknown. In the current study, we aimed to evaluate the impact of the OUD on outcomes in patients hospitalized with acute pancreatitis and delineate the trends associated with OUD and acute pancreatitis using a nationally representative sample. METHODS This is a retrospective cohort study of patients with acute pancreatitis using the combined releases of the year 2005-2014 of the National (Nationwide) Inpatient Sample (NIS) database. Patients over the age of 18 years with a principal diagnosis of acute pancreatitis were divided into cohorts of patients with opioid use disorders and those without. The primary measured outcome was in-hospital mortality and secondary outcomes were healthcare utilization measures, including length of stay (LOS) and hospitalization costs. RESULTS A total of 2 593 831 hospitalizations of acute pancreatitis were included; of which, 37 849 (1.46%) had a secondary diagnosis of OUD. Total acute pancreatitis-related hospitalizations increased from 237 882 in 2005 to 274 006 in 2014. At the same time prevalence of OUD in acute pancreatitis patients also increased from 1 to 2.1%. Patients with OUD had significantly increased mortality as compared to patients without OUD (aOR: 1.4; P

Objectives The aim of the study was to evaluate the effectiveness of BNT162b2 vaccine (Pfizer®) among healthcare workers (HCWs) while a recrudescence of pandemics was hitting the Brescia county, with a high rate of the B.1.1.7 variant. Methods The study was performed in the context of the mandatory health surveillance at the workplaces, in the period between 25th January 2021 and 26th March 2021, when 6904 HCWs (78% of workforce) gained full protection. HCWs were classified by having received the full vaccine schedule or not. The SARS-CoV-2 infection was diagnosed by conventional RT-PCR on rhino-pharyngeal swabs, followed by gene sequencing in positive vaccinated HCWs. Results We observed 84 SARS-CoV-2 infections among HCWs, most among unvaccinated HCWs. Gene sequencing was successful in 5 cases only, 4 B.1.1.7 and 1 B1.525 variants. In the same period, Lombardy registered 192.829 confirmed COVID-19 cases, 40.029 of which in Brescia county. The incidence rate of the B.1.1.7 variant rose from 70% to 97%. Conclusions Results confirm the protective effects of BNT162b2. The vaccine campaign was effective not only in reducing the appearance of symptoms but also in decreasing the incidence of infections among vaccinated HCWs. We observed a reduced infection rate also among the residual unvaccinated HCWs.

Background Breakthrough infections after SARS-CoV-2 infection have been reported. Clinical outcomes among persons with breakthrough infection are not known. Methods We retrospectively identified all Veterans with a confirmed SARS-CoV-2 infection >14 days after the second dose of either Pfizer-BNT-162b2 or Moderna-mRNA-1273 vaccine between December 15, 2020 and March 30, 2021, and age, race, sex, body mass index, Charlson comorbidity index, geographical location, and date of positive test matched unvaccinated controls with SARS-CoV-2 infection. Our primary endpoint was the rate of severe disease or death defined as hospitalization, admission to ICU, mechanical ventilation, or death in both groups. Findings Among 258,716 persons with both doses of vaccines and 756,150 without any vaccination, we identified 271 (0.1%) vaccinated persons with breakthrough infection and 48,114 (6.4%) unvaccinated matched controls with infection between December 15, 2020 and March 30, 2021. Among 213 matched pairs, symptoms were present in 33.3% of those with breakthrough infection and 42.2% of the controls. A total of 79 persons met the definition of severe disease or death (42 in the breakthrough infection group and 37 in the control group). Rate of severe disease or death per 1,000 person-days (95% CI) was 4.08 (2.84,5.31) among those with breakthrough infection and 3.6 (2.53,4.73) among the controls (P = 0.58). Rate was similar among both groups regardless of age-group, race, BMI or presence of comorbidities. Among persons with breakthrough infection and matched controls with infection, vaccination was not associated with a lower risk of severe disease or death in the main analyses but was associated with a lower risk when matching did not include geographic location (HR 0.62, 95% CI 0.43,0.91). Interpretation Demographic or clinical factors are not associated with a lower risk of severe disease or death in persons with breakthrough SARS-CoV-2 infection. Funding None

Introduction The Sars-Cov2 related COVID-19 pandemic has triggered the adoption of unprecedented approaches to contain it across the globe at a very short notice. The aim of this study is to determine post-operative mortality and the risk of developing COVID-19 in a COVID-19 negative population undergoing elective surgical care in a COVID-clean facility. We also explored patient experiences and satisfaction as well patient reported post-operative COVID related symptoms through a patient satisfaction survey. Method A patient satisfaction survey was built into the service which was performed by means of a telephone follow-up at 30 days from procedure. One of the aspects of the service review was to capture data on patients developing COVID-19 symptoms post-operatively but not requiring hospital admission or testing. Results & Conclusion: Our study has shown promising results with the early outcomes of elective surgical care delivered through a COVID-clean facility with no mortality, low morbidity and high patient satisfaction across all 5 specialties (Plastic surgery, Urology, Gynaecology, General Surgery) in 455 patients operated on over 10 weeks. We have demonstrated safe delivery of elective surgical services by utilising a COVID-clean facility minimising the negative impact of delays experienced due to the COVID-19 pandemic.

With population growth and aging, the emergence of new diseases and immunodeficiency, the demand for emergency departments (EDs) increases, making overcrowding in these departments a global problem. Due to the disease severity and transmission rate of COVID-19, it is necessary to provide an accurate and automated triage system to classify and isolate the suspected cases. Different triage methods for COVID-19 patients have been proposed as disease symptoms vary by country. Still, several problems with triage systems remain unresolved, most notably overcrowding in EDs, lengthy waiting times and difficulty adjusting static triage systems when the nature and symptoms of a disease changes. In this paper, we conduct a comprehensive review of general ED triage systems as well as COVID-19 triage systems. We identified important parameters that we recommend considering when designing an e-Triage (electronic triage) system for EDs, namely waiting time, simplicity, reliability, validity, scalability, and adaptability. Moreover, the study proposes a scoring-based e-Triage system for COVID-19 along with several recommended solutions to enhance the overall outcome of e-Triage systems during the outbreak. The recommended solutions aim to reduce overcrowding and overheads in EDs by remotely assessing patients’ conditions and identifying their severity levels.

Background Impact of SARS‐CoV‐2 infection upon hospitalization, intensive care unit (ICU) admissions and mortality in persons with hepatitis C virus (HCV) infection is unknown. Methods We used the Electronically Retrieved Cohort of HCV infected Veterans (ERCHIVES) database to determine the impact of HCV infection upon the rates of acute care hospitalization, ICU admission and all‐cause mortality. We identified Veterans with chronic HCV infection and propensity score matched controls without HCV in ERCHIVES. We excluded those with HIV or hepatitis B virus coinfection. Results We identified 975 HCV+ and 975 propensity score matched HCV− persons with SARS‐CoV‐2 infection. Mean FIB‐4 score (±SD) was higher in those with HCV (1.9 ± 2.1 vs 1.2 ± 0.9; P 3.25, the rate‐ was 9.4 and 0.6 (P

PRCIS: Telepresence robots present the versatility to effectively provide remote educational sessions for patients affected by glaucoma to improve disease knowledge. Given COVID-19's effect on clinical practice, telepresence robots can maintain social distancing when educating patients. PURPOSE: Telepresence robots (TR) are devices that allow remote users to have a mobile presence anywhere. We compared the effect of an education session given by an in-person educator versus a TR on glaucoma knowledge and identified factors that impact patient education. METHODS: Eighty-five glaucoma patients were split into control, human, and TR groups. We measured glaucoma knowledge scores (KS) using the National Eye Institute's Eye-Q Test. Human and TR groups had the education session with a human or TR followed by the questionnaire. The control group was administered the questionnaire without an education session. Treatment regimen recall (RR) greater than 90% was considered a success. We used linear regression and binary logistic regression to determine variables that affect KS and RR, respectively. RESULTS: Mean age was 58.3±2.8 years. 49% were female. Mean KS were 5.8±0.7 in the control group (n=31), 7.9±0.5 in the TR group (n=26), and 8.4±0.5 in the human group (n=28). Control participants had a lower mean KS than the human or TR groups (P

Melanin pigment helps protect our body from broad wavelength solar radiation and skin cancer. Among other pigmentation disorders in humans, albinism is reported to manifest in both syndromic and nonsyndromic forms as well as with varying inheritance patterns. Oculocutaneous albinism (OCA), an autosomal recessive nonsyndromic form of albinism, presents as partial to complete loss of melanin in the skin, hair, and iris. OCA has been known to be caused by pathogenic variants in seven different genes, so far, according to all the currently published population studies. However, the detection rate of alleles causing OCA varies from 50% to 90%. One of the significant challenges of uncovering the pathological variant underlying disease etiology is inter- and intra-familial locus heterogeneity. This problem is especially pertinent in highly inbred populations. As examples of such familial locus heterogeneity, we present nine consanguineous Pakistani families with segregating OCA due to variants in one or two different known albinism-associated genes. All of the identified variants are predicted to be pathogenic, which was corroborated by several in silico algorithms and association with diverse clinical phenotypes. We report an individual affected with OCA carries heterozygous, likely pathogenic variants in TYR and OCA2, raising the question of a possible digenic inheritance. Altogether, our study highlights the significance of exome sequencing for the complete genetic diagnosis of inbred families and provides the ramifications of potential genetic interaction and digenic inheritance of variants in the TYR and OCA2 genes.

Background & Aims Acetaminophen (APAP)-induced acute liver failure (ALF) remains the most common cause of ALF in the Western world. Conventional prognostic models, utilising markers of liver injury and organ failure, lack sensitivity for mortality prediction. We previously identified a microRNA signature that is associated with successful regeneration post-auxiliary liver transplant and with recovery from APAP-ALF. Herein, we aimed to use this microRNA signature to develop outcome prediction models for APAP-ALF. Methods We undertook a nested, case-control study using serum samples from 194 patients with APAP-ALF enrolled in the US ALF Study Group registry (1998-2014) at early (day 1-2) and late (day 3-5) time-points. A microRNA qPCR panel of 22 microRNAs was utilised to assess microRNA expression at both time-points. Multiple logistic regression was used to develop models which were compared to conventional prognostic models using the DeLong method. Results Individual microRNAs confer limited prognostic value when utilised in isolation. However, incorporating them within microRNA-based outcome prediction models increases their clinical utility. Our early time-point model (AUC = 0.78, 95% CI 0.71–0.84) contained a microRNA signature associated with liver regeneration and our late time-point model (AUC = 0.83, 95% CI 0.76–0.89) contained a microRNA signature associated with cell-death. Both models were enhanced when combined with model for end-stage liver disease (MELD) score and vasopressor use and both outperformed the King’s College criteria. The early time-point model combined with clinical parameters outperformed the ALF Study Group prognostic index and the MELD score. Conclusions Our findings demonstrate that a regeneration-linked microRNA signature combined with readily available clinical parameters can outperform existing prognostic models for ALF in identifying patients with poor prognosis who may benefit from transplantation. Lay summary While acute liver failure can be reversible, some patients will die without a liver transplant. We show that blood test markers that measure the potential for liver recovery may help improve identification of patients unlikely to survive acute liver failure who may benefit from a liver transplant.

Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.

We report the underlying genetic causes of prelingual hearing loss (HL) segregating in eight large consanguineous families, ascertained from the Punjab province of Pakistan. Exome sequencing followed by segregation analysis revealed seven potentially pathogenic variants, including four novel alleles c.257G>A, c.6083A>C, c.89A>G, and c.1249A>G of CLPP, CDH23, COL4A5, and LARS2, respectively. We also identified three previously reported HL-causing variants (c.4528C>T, c.35delG, and c.1219T>C) of MYO15A, GJB2, and TMPRSS3 segregating in four families. All identified variants were either absent or had very low frequencies in the control databases. Our in silico analyses and 3-dimensional (3D) molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MYO15A, GJB2, TMPRSS3, and CDH23 were classified as “pathogenic” or “likely pathogenic”, while the variants in CLPP and LARS2 fall in the category of “uncertain significance” based on the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant pathogenicity guidelines. This paper highlights the genetic diversity of hearing disorders in the Pakistani population and reports the identification of four novel mutations in four HL families.

Background Complicated intra-abdominal infections (cIAIs) are associated with significant morbidity and mortality. The aim of this study was to describe the clinical characteristics of patients with cIAI in a multicentre study and to develop clinical prediction models (CPMs) to help identify patients at risk of mortality or relapse. Methods A multicentre observational study was conducted from August 2016 to February 2017 in the UK. Adult patients diagnosed with cIAI were included. Multivariable logistic regression was performed to develop CPMs for mortality and cIAI relapse. The c-statistic was used to test model discrimination. Model calibration was tested using calibration slopes and calibration in the large (CITL). The CPMs were then presented as point scoring systems and validated further. Results Overall, 417 patients from 31 surgical centres were included in the analysis. At 90 days after diagnosis, 17.3 per cent had a cIAI relapse and the mortality rate was 11.3 per cent. Predictors in the mortality model were age, cIAI aetiology, presence of a perforated viscus and source control procedure. Predictors of cIAI relapse included the presence of collections, outcome of initial management, and duration of antibiotic treatment. The c-statistic adjusted for model optimism was 0.79 (95 per cent c.i. 0.75 to 0.87) and 0.74 (0.73 to 0.85) for mortality and cIAI relapse CPMs. Adjusted calibration slopes were 0.88 (95 per cent c.i. 0.76 to 0.90) for the mortality model and 0.91 (0.88 to 0.94) for the relapse model; CITL was −0.19 (95 per cent c.i. −0.39 to −0.12) and − 0.01 (− 0.17 to −0.03) respectively. Conclusion Relapse of infection and death after complicated intra-abdominal infections are common. Clinical prediction models were developed to identify patients at increased risk of relapse or death after treatment, these now require external validation.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (>50%) were reported. APPROACH AND RESULTS: Median age was 36.3 years (range, 2–80), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and/or BCP variants increased from 14.4% in the first two decades to 51% after 40 years of age. Among those aged 2–18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001). CONCLUSIONS: PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(−) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.

Conceptual design and modification of urea moiety in chemotype PF-3845/04457845, the bench marking irreversible inhibitor of fatty acid amide hydrolase (FAAH), led to discovery of a novel nicotinamide-based lead 12a having reversible mechanism of action. Focused SAR around the pyridine heterocycle (Ar) in 12a (Tables 1 and 2) resulted into four shortlisted compounds, (−)-12a, (−)-12i, (−)-12l–m. The required (−)-enantiomers were obtained via diastereomeric resolution of a novel chiral dissymmetric intermediate 15. Based on comparative profile of FAAH potency, metabolic stability in liver microsome, liability of inhibiting major hCYP450 isoforms, rat PK, and brain penetration ability, two SAR optimized compounds, (−)-12l and (−)-12m, were selected for efficacy study in rat model of chemotherapy-induced peripheral neuropathy (CIPN). Both the compounds exhibited dose related antihyperalgesic effects, when treated with 3–30 mg/kg po for 7 days. The effects at 30 mg/kg are comparable to that of PF-04457845 (10 mg/kg) and Tramadol (40 mg/kg).

Two series of carbazole analogs of 8-methoxy-N-substituted-9H-carbazole-3-carboxamides (series 1) and carbazolyl substituted rhodanines (series 2) were synthesized through facile synthetic routes. All the final compounds from these two series were evaluated for their preliminary in vitro antifungal and antibacterial activity against four fungal (Candida albicans, Cryptococcus neoformans, Cryptococcus tropicalis and Aspergillus niger) and four bacterial (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa) strains, respectively. Among the tested compounds, three compounds of series 1 displayed promising antifungal and antibacterial activity, especially against C. neoformans and S. aureus. In addition, one compound of series 1 displayed notable antimicrobial activity (MIC: 6.25 μg/mL) against clinical isolates of C. albicans and C. neoformans (MIC: 12.5 μg/mL). From the second series, four compounds exhibited significant antifungal and antibacterial activity, especially against C. neoformans and S. aureus. The most active compound of series 2 displayed a prominent antimicrobial activity against C. neoformans (MIC: 3.125 μg/mL) and S. aureus (MIC: 1.56 μg/mL), respectively.

Introduction The Wirral Teletriage Service provides non-urgent clinical support to Wirral Care Homes in order to help avoid unnecessary hospital admissions for their residents. It also aims to provide quicker access to clinical assessment than via NHS 111 and to provide this care in the patient’s residence wherever possible. Methods Care homes call the Teletriage service when they have concerns about the health of one of their residents. The Teletriage nurse undertakes a clinical assessment of the resident remotely via Skype. Care Homes have been provided with a secure NHS email address to facilitate secure sharing of data. They have also been provided with iPads and training for their staff. After being assessed by Teletriage, residents are signposted to the most appropriate care pathway for their needs. Results 76 Care Homes have signed up to the service. On average, the Teletriage Service receives 300-400 calls a month. In an 18 month period, the number of calls to NHS 111 have reduced by 76%. Out of all the calls to Teletriage, 22% of patients were managed by the Teletriage team with no onward referral, 57% were managed via community services e.g GPs, Community Geriatricians, and 10% were referred to the ambulance service. Emergency Health Care Plans (EHCPs), Preferred Priorities of Care and EOL (End of Life) wishes are taken into account. Conclusions The Teletriage project has reduced the number of phone calls to NHS 111 and the ambulance service, and subsequently has reduced the number of patients conveyed to hospital by 12%. The Teletriage nurses work very closely with various community services as well as GPs, NWAS and Community Geriatricians. The ongoing training and education provided to the Care Home Staff means that overall there has been good engagement with the project from the majority of the Wirral Care Homes.

Siderophores are small molecular weight (generally 1 kDa) ferric specific ligands produced by variety of organisms to chelate iron under iron limiting conditions. Various assays have been in use to detect and estimate different phenotypes of siderophores. Though there are various methods available for detection of iron specific siderophore or modified method for Cu specific siderophore [chalkophore], reports on modified methods for detection of siderophore having affinity for various other metal ions are scarce. In present study, a modified method was designed for screening siderophores that can bind to heavy metal ions such as Cu2+, Ni2+, Mn2+, Co2+, Zn2+, Hg2+ and Ag2+. Each of the modified chrome azurol S (CAS) solution when used to screen siderophore resulted in instant colour change similar to the traditionally used CAS solution for screening Fe3+ specific siderophores. Two bacterial cultures isolated from local rhizospheric soil produced hydroxamate and catecholate siderophores that could remove Cu2+, Ni2+, Mn2+, Co2+, Zn2+, Hg2+ and Ag2+ metal ions from CAS solution resulting in instant colour change. Similar observations were recorded on CAS agar amended with modified CAS solution. The order of complexation of metals with siderophore produced by Alcaligenes sp. RZS2 in CAS assay was as follows; Cu2+ > Ni2+ > Mn2+ > Fe3+ > Co2+ > Zn2+ > Hg2+ > Ag2+. The order of complexation of metals with siderophore produced by Pseudomonas aeruginosa RZS3 in CAS assay was as follows; Ni2+ > Co2+ > Mn2+ > Zn2+ > Fe3+ > Cu2+ > Hg2+ > Ag2+.

Acetaminophen (APAP)-induced acute liver failure (ALF) is a rare disease associated with high mortality rates. This study aimed to evaluate changes in interventions, psychosocial profile, and clinical outcomes over a 21-year period using data from the ALF Study Group registry.A retrospective review of this prospective, multicenter cohort study of all APAP-ALF patients enrolled during the study period (1998-2018) was completed. Primary outcomes evaluated were the 21-day transplant-free survival (TFS) and neurologic complications. Covariates evaluated included enrollment cohort (early, 1998-2007; recent, 2008-2018), intentionality, psychiatric comorbidity, and use of organ support including continuous renal replacement therapy (CRRT).Of 1190 APAP-ALF patients, recent cohort patients (n = 608) had significantly improved TFS (recent, 69.8% vs early, 61.7%; P = .005). Recent cohort patients were more likely to receive CRRT (22.2% vs 7.6%; P.001), and less likely to develop intracranial hypertension (29.9% vs 51.5%; P.001) or die by day 21 from cerebral edema (4.5% vs 11.6%; P.001). Grouped by TFS status (non-TFS, n = 365 vs TFS, n = 704), there were no differences in psychiatric comorbidity (51.5% vs 55.0%; P = .28) or intentionality (intentional, 39.7% vs 41.6%; P = .58). On multivariable logistic regression adjusting for vasopressor support, development of grade 3/4 hepatic encephalopathy, King's College criteria, and MELD score, the use of CRRT (odds ratio, 1.62; P = .023) was associated with significantly increased TFS (c-statistic, 0.86). In a second model adjusting for the same covariates, recent enrollment was associated significantly with TFS (odds ratio, 1.42; P = .034; c-statistic, 0.86).TFS in APAP-ALF has improved in recent years and rates of intracranial hypertension/cerebral edema have decreased, possibly related to increased CRRT use.

Displacement of leads due to coiling around the pacemaker in the sagittal axis can result in Reel syndrome. Rotation of pulse generator can be due to self-manipulation, ratchet-like mechanism, or due to enlarged pocket. Our case presented with complete heart block with lead displacement and protrusion of pulse generator. Chest X-ray was suggestive of Reel syndrome. The pacemaker was explanted and implanted on the other side. To prevent recurrence, adequate pocket size was created with proper suturing to the underlying fascia and adequate compression for 5–7 days was applied after implantation.