Drug use survey to identify significant drug-drug interactions and assess clinical importance in the outpatient setting of a tertiary care hospital.

OBJECTIVES: Drug-drug interactions (DDIs) are a common problem in pharmacotherapy, particularly in situations where multiple disorders must be treated at the same time. We conducted a drug use survey in the general medicine outpatient department of a tertiary care hospital with the objective of assessing the potential for DDI in individual prescriptions for adult patients. MATERIALS AND METHODS: Drugs prescribed in the current physician-patient encounter were considered in conjunction with medicines already being received by the patient as well as those discontinued in the past 1 month. Free online DDI checkers (available at https://www.drugs.com/drug_interactions.html and https://reference.medscape.com/) were used to identify potential DDI and categorize them into mild, moderate, and severe categories. We did not consider food, alcohol, or smoking-related interactions. RESULTS: A total of 153 prescriptions, having two or more drugs, were collected, and they accounted for 1052 prescribed drugs. Among them, 613 (58.27%) were prescribed in index visits, and the rest 438 (41.63%) were preexisting medication. The number of drugs prescribed in index visits ranged from 1 to 9 (mean ± standard deviation [SD] 4.0 ± 1.86; median 4). Potential DDIs were identified in 103 (67.32%) instances. The total number of interactions identified was 412. Of these, 19.66% had minor, 77.67% moderate, and 7.19% major clinical implications. Potential DDI count in each prescription was found from 0 to 13 in number (mean ± SD 2.7 ± 3.12; median 2.0). This number correlated strongly with the number of drugs being received by individual subjects (Rho 0.744; P < 0.001). CONCLUSIONS: Potential DDIs are a reality in day to day prescribing practice. Substantial proportion of these DDIs may have significant clinical implications. Prescribers need to be sensitized to this issue. Combining human expertise with technological solutions such as automated drug interaction alerts can help rectify the situation. Similar surveys are needed on a periodic basis to improve medication safety for patients.

Corrigendum to: "Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results" [JHEP Reports 5 (2019) 101041].

[This corrects the article DOI: 10.1016/j.jhepr.2019.10.006.].

Tracking Missing Deaths: An Exploratory Study on the Mortality Impact of COVID-19 in Kozhikode City, India.

BACKGROUND: The debate over the extent of the mortality impact of COVID-19 in India is still unsettled. OBJECTIVES: This article contributes to the debate, seeking to explore the true mortality impact of the pandemic, by answering four interrelated questions. First, is there any discrepancy between recorded and actual death count? Second, if so, how large it is? Third, what is the extent of misclassification of COVID-19 mortality, and fourth, what is the magnitude of deaths that could be indirectly linked to COVID-19? MATERIALS AND METHODS: To answer the questions, we explored three sources of data-all-cause mortality data from the civil registration system, records maintained at the burial grounds/cemeteries and crematoriums, and a household survey. The data collection period was between August 2021 and November 2021. The instrument used for data collection of verbal autopsies was built on the instrument proposed by the World Health Organization for adult mortality. RESULTS: The results revealed that deaths due to various causes including COVID-19 increased considerably at some points in 2020-2021 compared to the base year 2019 in the study setting. Notably, 5.5% of the noninstitutional deaths were unreported at the time of the survey and many deaths were plausibly misclassified, leading to undercounting of COVID-19 deaths. Overall, about half of our sampled deaths (48%) had either direct or indirect attribution to the pandemic. CONCLUSION: The extent of undercounting of pandemic-related deaths is likely to be either similar or worse in other states. To get reliable state and national estimates, policymakers should conduct a large-scale study.

Neutral or Detrimental Effects of TREM2 Agonist Antibodies in Preclinical Models of Alzheimer's Disease and Multiple Sclerosis.

Human genetics and preclinical studies have identified key contributions of TREM2 to several neurodegenerative conditions, inspiring efforts to modulate TREM2 therapeutically. Here, we characterize the activities of three TREM2 agonist antibodies in multiple mixed-sex mouse models of Alzheimer's disease (AD) pathology and remyelination. Receptor activation and downstream signaling are explored in vitro, and active dose ranges are determined in vivo based on pharmacodynamic responses from microglia. For mice bearing amyloid-ß (Aß) pathology (PS2APP) or combined Aß and tau pathology (TauPS2APP), chronic TREM2 agonist antibody treatment had limited impact on microglia engagement with pathology, overall pathology burden, or downstream neuronal damage. For mice with demyelinating injuries triggered acutely with lysolecithin, TREM2 agonist antibodies unexpectedly disrupted injury resolution. Likewise, TREM2 agonist antibodies limited myelin recovery for mice experiencing chronic demyelination from cuprizone. We highlight the contributions of dose timing and frequency across models. These results introduce important considerations for future TREM2-targeting approaches.

A Study of Prevalence of Renal Function Abnormalities and Their Association with the Individual Components of Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is one of the most important emerging pandemics of the 21st century and is associated with renal dysfunction in a significant number of subjects, the association of which is shown to be of greater significance in the South Asian population. AIMS AND OBJECTIVES: The prevalence of renal dysfunction in patients with MetS is the primary outcome. The secondary outcome is to assess the strength and significance of the association between the individual components of MetS and the presence of renal dysfunction. MATERIALS AND METHODS: This is a hospital-based cross-sectional observational study conducted for 2 years in a tertiary care hospital in India. A total of 100 diagnosed subjects of MetS were taken as cases and underwent relevant blood tests. Data were collected and analyzed in a Statistical Package for the Social Sciences (SPSS) v29 sheet. RESULTS: Over a period of 18 months, 100 subjects with MetS were documented, among which 66% had albuminuria, with microalbuminuria being 24% and the rest being macroalbuminuria. Among the same subjects, 30% had an estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73m2. Waist circumference (WC) [measured by the National Institutes of Health (NIH) protocol] had the strongest association with increased albuminuria (r = 0.540; p-value < 0.001) as well as reduced eGFR (r = 0.460; p-value < 0.001). CONCLUSION: All the components of MetS, for example, increased WC, hypertension, increased fasting glucose, raised triglyceride (TG), and low high-density lipoprotein (HDL), have statistically significant correlations with increased urine albumin-to-creatinine ratio (ACR) and decreased eGFR, signifying glomerular injury and renal dysfunction, respectively.

Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

Predicting multi-label emojis, emotions, and sentiments in code-mixed texts using an emojifying sentiments framework.

In the era of social media, the use of emojis and code-mixed language has become essential in online communication. However, selecting the appropriate emoji that matches a particular sentiment or emotion in the code-mixed text can be difficult. This paper presents a novel task of predicting multiple emojis in English-Hindi code-mixed sentences and proposes a new dataset called SENTIMOJI, which extends the SemEval 2020 Task 9 SentiMix dataset. Our approach is based on exploiting the relationship between emotion, sentiment, and emojis to build an end-to-end framework. We replace the self-attention sublayers in the transformer encoder with simple linear transformations and use the RMS-layer norm instead of the normal layer norm. Moreover, we employ Gated Linear Unit and Fully Connected layers to predict emojis and identify the emotion and sentiment of a tweet. Our experimental results on the SENTIMOJI dataset demonstrate that the proposed multi-task framework outperforms the single-task framework. We also show that emojis are strongly linked to sentiment and emotion and that identifying sentiment and emotion can aid in accurately predicting the most suitable emoji. Our work contributes to the field of natural language processing and can help in the development of more effective tools for sentiment analysis and emotion recognition in code-mixed languages. The codes and data will be available at https://www.iitp.ac.in/~ai-nlp-ml/resources.html#SENTIMOJI to facilitate research.

ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.

There are significant commonalities among several pathologies involving fibroblasts, ranging from auto-immune diseases to fibrosis and cancer. Early steps in cancer development and progression are closely linked to fibroblast senescence and transformation into tumor-promoting cancer-associated fibroblasts (CAFs), suppressed by the androgen receptor (AR). Here, we identify ANKRD1 as a mesenchymal-specific transcriptional coregulator under direct AR negative control in human dermal fibroblasts (HDFs) and a key driver of CAF conversion, independent of cellular senescence. ANKRD1 expression in CAFs is associated with poor survival in HNSCC, lung, and cervical SCC patients, and controls a specific gene expression program of myofibroblast CAFs (my-CAFs). ANKRD1 binds to the regulatory region of my-CAF effector genes in concert with AP-1 transcription factors, and promotes c-JUN and FOS association. Targeting ANKRD1 disrupts AP-1 complex formation, reverses CAF activation, and blocks the pro-tumorigenic properties of CAFs in an orthotopic skin cancer model. ANKRD1 thus represents a target for fibroblast-directed therapy in cancer and potentially beyond.

Cross-sectional study on the psychosocial factors, the severity of depression, and coping strategies among patients attempting suicide.

Background: With around 10-20 million individuals attempting suicide each year, suicide attempts have been considered a significant public health issue. A significant fraction of it is caused by depression. Life events and other psychosocial stressors were frequently linked to both depression and suicidal behavior. Coping strategies are cognitive, emotional, and behavioral approaches used to lessen and cope with the negative impacts of stressful situations. Aim: This study aimed to find the psychosocial factors, the severity of depression, and coping strategies among patients attempting suicide. Materials and Methods: Study design: This study was a hospital-based descriptive cross-sectional study. A total of 120 consecutive cases were selected using Patient Health Questionnaire 2 (PHQ-2) scales and assessed for severity of depression and coping strategies using the Hamilton Depression Rating Scale (HAM-D) and Coping Orientation to Problem Experienced Inventory (Brief-COPE) scales, respectively. Pearson's Chi-square or Fisher's exact test and independent-samples t-test have been performed to see the association between categorical and continuous variables. The Pearson correlation coefficient has been used to see the relationship between two continuous variables. Results: Most of the cases (33.3%) were found to be severely depressed. Among all the cases, the majority, that is, 90.8%, were using avoidant-type coping strategies and only 9.2% were using approach-type coping strategies. A significant positive correlation between the avoidant-type coping strategy and depression and a negative correlation between the approach-type coping strategy and depression was found. Conclusion: Patients with depression attempting suicide were found to utilize avoidant-type coping strategies to cope with life stresses. Hence, it is crucial to place greater emphasis on assessing coping strategies and focus on teaching approach-oriented coping strategies as a means to prevent suicidal attempts.

A fluorescent splice-switching mouse model enables high-throughput, sensitive quantification of antisense oligonucleotide delivery and activity.

While antisense oligonucleotides (ASOs) are used in the clinic, therapeutic development is hindered by the inability to assay ASO delivery and activity in vivo. Accordingly, we developed a dual-fluorescence, knockin mouse model that constitutively expresses mKate2 and an engineered EGFP that is alternatively spliced in the presence of ASO to induce expression. We first examined free ASO activity in the brain following intracerebroventricular injection revealing EGFP splice-switching is both ASO concentration and time dependent in major central nervous system cell types. We then assayed the impact of lipid nanoparticle delivery on ASO activity after intravenous administration. Robust EGFP fluorescence was observed in the liver and EGFP+ cells were successfully isolated using fluorescence-activated cell sorting. Together, these results show the utility of this animal model in quantifying both cell-type- and organ-specific ASO delivery, which can be used to advance ASO therapeutics for many disease indications.

Early and mid-term outcomes of double-chambered right ventricle repair: An 8-year experience.

BACKGROUND/AIM: Double-chambered right ventricle is a rare and progressive condition that is characterised by obstruction of the right ventricular tract. Double-chambered right ventricle is usually associated with ventricular septal defect. Early surgical intervention is recommended in patients with these defects. Based on this background, the present study aimed to review early and midterm outcomes of primary repair after double-chambered right ventricle. METHODS: Between January 2014 and June 2021, 64 patients with a mean age of 13.42 ± 12.31 years underwent surgical repair for double-chambered right ventricle. The clinical outcomes of these patients were reviewed and assessed retrospectively. RESULTS: An associated ventricular septal defect was present in all the recruited patients; 48 (75%) patients of sub-arterial type, 15 (23.4%) of perimembranous, and 1 (1.6%) patient of muscular type. The patients were followed up for a mean period of 46.73 ± 27.37 months. During their follow-up, a significant decrease in the mean pressure gradient from 62.33 ± 5.52 mmHg preoperatively to 15.73 ± 2.94 mmHg postoperatively was observed (p < 0.001). Notably, there were no hospital deaths. CONCLUSIONS: The development of double-chambered right ventricle in association with ventricular septal defect results in an increased pressure gradient within the right ventricle. The defect needs correction in a timely manner. In our experience, the surgical correction of double-chambered right ventricle is safe and shows excellent early and mid-term results.

Relation of Vitamin D levels with positive and negative symptoms of schizophrenia - A hospital based cross-sectional comparative study.

Background: The association between altered serum Vitamin D levels and schizophrenia has been an area that has evoked a recent fervor. The neurohumoral and neuro immunomodulatory functions of Vitamin D might have a role to play in understanding the causation of the disease and thus appear promising in the diagnostic and therapeutic frontiers of the disease. Aims and Objectives: We aimed to estimate and compare serum Vitamin D levels in drug-free cases of schizophrenia and in healthy control groups. The comparison was also made among the subgroups of positive and negative schizophrenia. Materials and Methods: The study, a hospital-based cross-sectional comparative study was carried out in the Department of Psychiatry, in a hospital in Assam over a period of 1 year. Fifty drug-free subjects of schizophrenia (Group A) diagnosed and confirmed according to International Classification of Diseases 10 were selected by consecutive sampling and 50 age and sex frequency-matched subjects (Group B) were selected from the healthy population. The cases (Group A) were divided into positive and negative groups (Group A1 and A2) based on the composite scoring of the Positive and Negative Syndrome Scale. After approval from the institutional ethics committee and obtaining written informed consent, Vitamin D levels were assessed in both groups of cases and controls and comparison was made. Results: After statistical analysis, it was seen that males were more in proportion and mostly in the age group of 20-39 years. The median Vitamin D level among the cases was 12.45 ng/mL and that among controls was 20.03 ng/mL which was statistically significant (P value .00932). Among the positive and negative schizophrenia subgroup, there was no statistically significant difference in Vitamin D levels at means of 16.54 ng/mL and 16.25 ng/Ml, respectively. The variation in Vitamin D levels in schizophrenics and the healthy population is thus discernible. Conclusion: It can be said that serum Vitamin D levels were significantly low in people with schizophrenia compared to the general population. Furthermore, it is seen that mean Vitamin D status is similar in both the groups of positive and negative schizophrenia negating the possibility of alteration of Vitamin D levels depending on the differences in symptomatology or in pathophysiology of the two groups.

Early and Mid-Term Outcomes of Primary Repair After Atrioventricular Canal Defect: A Single-Center Eight-Year Experience.

BACKGROUND/AIM: Surgical repair techniques and management of patients with atrioventricular septal defect (AVSD) have progressed over the last few decades. Early and definitive interventions have become the choice of treatment for these patients. Based on this background, we aimed to review the early and mid-term outcomes of primary AVSD repair. METHODS: A total of 53 patients with a mean age of 3.45 ± 5.67 years underwent definitive repair for AVSD between January 2014 and June 2021. The clinical data including age, type of defect, associated co-anomalies, symptoms, pulmonary hypertension, etc. were collected and assessed retrospectively. Mitral regurgitation (MR) as a clinical outcome was assessed at 0, 1, 2, and 5 years. RESULTS: Among the recruited patients, 35 (66.1%) were male and 18 (33.9%) were female. Of 53 patients, repair for the complete defect was done in 38 (71.69%) patients, repair for intermediate/partial defect was done in 15 (23.1%) patients, and one patient underwent repair for incomplete type. Other associated co-anomalies were anterior mitral leaflet (12 (22.6%)), atrial and ventricular septal defect (VSD) (30 (56.6%)), and patent ductus arteriosus (PDA) (11 (20.8%)). Different procedures for surgical repair included patch closure, cleft repair, and polytetrafluoroethylene (PTFE) VSD closure. After repair, the mean follow-up period was 46.73 ± 27.37 months. Overall mortality was 3.78% (2/53), and two patients underwent reintervention due to symptomatic severe MR. CONCLUSIONS: A definitive and timely correction of AVSD shows satisfactory early and mid-term results.

Effectiveness and Safety of the Ozaki Procedure for Aortic Valve Disease in Pediatric Patients: A Systematic Review and Meta-Analysis.

The surgical treatment options for pediatric aortic valve disease are limited and have debatable long-term durability. In the current situation, the Ross procedure is considered in children for aortic valve disease(s). It is a complex surgical procedure with the risk of neo-aortic dilatation, converting a single valve disease into double valve disease, and associated with future re-interventions. Conversely, the Ozaki procedure has shown promising results in adults. Thus, the present study aimed to provide comparative evidence on the effectiveness and safety of the Ozaki versus Ross procedure for pediatric patients by performing a meta-analytic comparison of reporting outcomes. A total of 15 relevant articles were downloaded and among them, seven articles (one prospective study, five retrospective studies, and one case series) were used in the analysis. Primary outcomes such as physiological laminar flow pattern and hemodynamic parameters, and secondary outcomes such as hospital stays, adverse effects, mortality, and numbers of re-intervention(s) were measured in the meta-analysis. There were no significant differences in the age of patients between children who underwent the Ozaki procedure and those who underwent the Ross procedure at the time of surgeries. The Ozaki procedure is a good solution to an aortic problem(s) similar to the Ross procedure. Unlike the Ross procedure, the Ozaki procedure has restored a physiological laminar flow pattern in the short-term follow-up without the bi-valvular disease. Mean hospital stays (p = 0.048), mean follow-up (p = 0.02), adverse effects (p = 0.02), death, and numbers of re-intervention(s) of children who underwent the Ozaki procedure were fewer than those who underwent the Ross procedure. The time required for re-intervention(s) is higher for children who underwent the Ozaki procedure than those who underwent the Ross procedure. None of the procedures, including the Ozaki procedure for aortic valve disease(s), has significant effects on hemodynamic parameters and the frequent death rate of children after surgeries. Based on our analysis, we may suggest the Ozaki procedure for aortic valve disease surgery in children.

Androgen receptor is a determinant of melanoma targeted drug resistance.

Melanoma provides a primary benchmark for targeted drug therapy. Most melanomas with BRAFV600 mutations regress in response to BRAF/MEK inhibitors (BRAFi/MEKi). However, nearly all relapse within the first two years, and there is a connection between BRAFi/MEKi-resistance and poor response to immune checkpoint therapy. We reported that androgen receptor (AR) activity is required for melanoma cell proliferation and tumorigenesis. We show here that AR expression is markedly increased in BRAFi-resistant melanoma cells, and in sensitive cells soon after BRAFi exposure. Increased AR expression is sufficient to render melanoma cells BRAFi-resistant, eliciting transcriptional changes of BRAFi-resistant subpopulations, including elevated EGFR and SERPINE1 expression, of likely clinical significance. Inhibition of AR expression or activity blunts changes in gene expression and suppresses proliferation and tumorigenesis of BRAFi-resistant melanoma cells, promoting clusters of CD8+ T cells infiltration and cancer cells killing. Our findings point to targeting AR as possible co-therapeutical approach in melanoma treatment.

A rare presentation of dengue fever: bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia.

Dengue is the foremost cause of arthropod-borne viral disease in the world. It is and commonly found in tropical and subtropical parts of the world. Dengue fever is caused by one of the four distinct serotypes (DENV 1-4) of single-stranded RNA Flavivirus genus and transmitted through Aedes mosquito. Infection caused by one serotype develops lifelong immunity to that serotype, but not to others. Dengue fever (DF) presents with high fever, headache, myalgia, and arthralgia, and rash. Severe dengue, dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS) are accompanied by thrombocytopenia, vascular leakage, and hypotension. DSS is characterized by shock, which can be fatal with case fatality high as 12% to 44%. There are few atypical manifestations of dengue fever growing with rising disease burden, often missed and sometimes difficult to diagnosis. In this case report, we will discuss atypical manifestations of bilateral psoas muscle hematoma, intrahepatic cholestatic hepatitis, pancreatitis and pancytopenia observed in dengue fever patient.

Surgical Outcomes of Post-myocardial Infarction Ventricular Septal Defect/Rupture: A Systematic Review and Meta-Analysis.

Ventricular septal defect (VSD) is a catastrophic acute myocardial infarction (MI) complication. Despite a significant reduction in the prevalence of post-MI VSD with the advancement of surgical techniques, it is still considered fatal with a high mortality rate. The trends in the clinical outcomes of patients with post-MI VSD show discretion due to the complexity of the disease. Therefore, the present analysis aimed to evaluate the surgical outcomes and associated risks in the patients of post-MI VSD. A thorough literature survey resulted in 40 studies of our interest. The pooled proportion of differential variables, including the incidence of cardiogenic shock, 30-day survival, and overall mortality, were estimated using Bayesian hierarchical models. The risk difference was estimated for the location of MI and VSD and mortality in patients with coronary artery bypass graft (CABG). In addition, the heterogeneity tests for inconsistency and publication biases using Egger's and Begg's tests were also estimated. The analysis revealed a significant risk difference of 0.23 and 0.27 for the anterior vs. posterior location of MI and VSD, respectively. Further, the pooled proportion of 30-day survival and mortality was found to be 54.43% (95% credible interval (CI): 52.88-55.98%) and 48.22% (95% CI: 4-12.3%), respectively. Moreover, the heterogeneity test revealed significant inconsistencies in all the datasets with an I2 index of >90% (p<0.0001). Lastly, the publication bias results suggested no evidence of asymmetry and small-study effects. Conclusively, the surgical management of post-MI VSD patients is considered beneficial; however, the outcomes signify its fatal behavior.

Nuclear lamin A/C phosphorylation by loss of Androgen Receptor is a global determinant of cancer-associated fibroblast activation.

Alterations of nuclear structure and function, and associated impact on gene transcription, are a hallmark of cancer cells. Little is known of these alterations in Cancer-Associated Fibroblasts (CAFs), a key component of the tumor stroma. Here we show that loss of androgen receptor (AR), which triggers early steps of CAF activation in human dermal fibroblasts (HDFs), leads to nuclear membrane alterations and increased micronuclei formation, which are unlinked from induction of cellular senescence. Similar alterations occur in fully established CAFs, which are overcome by restored AR function. AR associates with nuclear lamin A/C and loss of AR results in a substantially increased lamin A/C nucleoplasmic redistribution. Mechanistically, AR functions as a bridge between lamin A/C with the protein phosphatase PPP1. In parallel with a decreased lamin-PPP1 association, AR loss results in a marked increase of lamin A/C phosphorylation at Ser 301, which is also a feature of CAFs. Phosphorylated lamin A/C at Ser 301 binds to the transcription promoter regulatory region of several CAF effector genes, which are upregulated due to the loss of AR. More directly, expression of a lamin A/C Ser301 phosphomimetic mutant alone is sufficient to convert normal fibroblasts into tumor-promoting CAFs of the myofibroblast subtype, without an impact on senescence. These findings highlight the pivotal role of the AR-lamin A/C-PPP1 axis and lamin A/C phosphorylation at Ser 301 in driving CAF activation.

Surgical outcomes of double-orifice mitral valve repair in patients with atrioventricular canal defects: a systematic review and meta-analysis.

INTRODUCTION: Double-orifice mitral valve or left atrioventricular valve is a rare congenital cardiac anomaly that may be associated with an atrioventricular septal defect. The surgical management of double-orifice mitral valve/double-orifice left atrioventricular valve with atrioventricular septal defect is highly challenging with acceptable clinical outcomes. This meta-analysis is aimed to evaluate the surgical outcomes of double-orifice mitral valve/double-orifice left atrioventricular valve repair in patients with atrioventricular septal defect. METHODS AND RESULTS: A total of eight studies were retrieved from the literature by searching through PubMed, Google Scholar, Embase, and Cochrane databases. Using Bayesian hierarchical models, we estimated the pooled proportion of incidence of double-orifice mitral valve/double-orifice left atrioventricular valve with atrioventricular septal defect as 4.88% in patients who underwent surgical repair (7 studies; 3295 patients; 95% credible interval [CI] 4.2-5.7%). As compared to pre-operative regurgitation, the pooled proportions of post-operative regurgitation were significantly low in patients with moderate status: 5.1 versus 26.39% and severe status: 5.7 versus 29.38% [8 studies; 171 patients]. Moreover, the heterogeneity test revealed consistency in the data (p < 0.05). Lastly, the pooled estimated proportions of early and late mortality following surgical interventions were low, that is, 5 and 7.4%, respectively. CONCLUSION: The surgical management of moderate to severe regurgitation showed corrective benefits post-operatively and was associated with low incidence of early mortality and re-operation.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.