Severe and rapidly changing hypophosphatemia in cannabinoid hyperemesis syndrome: a case report.

The increasing prevalence of cannabis worldwide requires awareness of a potential, less recognized, paradoxical entity, the cannabinoid hyperemesis syndrome (CHS). This includes cyclic episodes of nausea, vomiting, and compulsive hot water bathing for alleviation in individuals with chronic cannabis use. An 18-year-old male with daily and prolonged cannabis use has excessive nausea and vomiting, is diagnosed with CHS, and is further complicated by severe and rapidly fluctuating hypophosphatemia. He was successfully managed with intravenous (IV) antiemetic (metoclopramide) and IV normal saline in the emergency department. Hypophosphatemia was treated with IV phosphorous. Although hypophosphatemia in CHS is a rare encounter, the authors share their experience to promote broader recognition and insight into successful management.

Comparison of efficacy of intercostal nerve block versus peritract infiltration with 0.25% bupivacaine in percutaneous nephrolithotomy: A prospective randomized clinical trial.

Introduction: Postoperative pain following percutaneous nephrolithotomy (PCNL) adds to the morbidity of patients requiring additional analgesia. Various modalities of pain control techniques, such as intercostal nerve block (ICNB) and peritract infiltration (PTI), are being studied for better pain management. This study compares the efficacy of ICNB with PTI for postoperative pain management. Methods: A double-blinded, prospective, randomized control study was conducted, in which 0.25% bupivacaine, either ICNB or PTI, was given at the puncture site at the end of PCNL. The primary outcome was a comparison of postoperative pain score measured with resting Visual analogue Scale (r-VAS) and dynamic VAS (D-VAS) recorded at 2 h, 4 h, 8 h, 10 h, 12 h, 24 h, and at discharge. Injection ketorolac was given as rescue analgesia. Secondary outcomes include time to first rescue analgesia and total analgesic requirement (TAR). Results: Sixty patients were randomized into two equal groups with 63.3% male and 36.6% female, with a mean age of 37.25 ± 13.09 years. In Group ICNB, 24 (40%) and 6 (10%) patients and in Group PTI, 21 (35%) and 9 (15%) patients underwent standard and mini PCNL, respectively, in each group. All cases were PCNL doen in prone position. The mean R-VAS and D-VAS scores at 2, 4, 8, 12, 24, and 48 h were similar in both groups. The mean TAR was 56.84 ± 0.33.00 mg and 55.54 ± 0.29.64 mg of injection ketorolac in Group ICNB and PTI, respectively (P < 0.894). The time to first rescue analgesic demand were 7.11 ± 4.898 h and 6.25 ± 3.354 h (P < 0.527). Both the groups were comparable in terms of length of hospital stay, stone clearance rate, and complication rate. Conclusion: The ICNB was as efficacious as PTI for postoperative pain control with 0.25% bupivacaine following PCNL.

Safety and efficacy of prophylactic anticoagulation versus therapeutic anticoagulation in hospital-admitted COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: COVID-19 disease-related coagulopathy and thromboembolic complication, an important aspect of the disease pathophysiology, are frequent and associated with poor outcomes, particularly significant in hospitalized patients. Undoubtedly, anticoagulation forms a cornerstone for the management of hospitalized COVID-19 patients, but the appropriate dosing has been inconclusive and a subject of research. We aim to review existing literature and compare safety and efficacy outcomes of prophylactic and therapeutic dose anticoagulation in such patients. METHODS: We did a systematic review and meta-analysis to compare the efficacy and safety of prophylactic dose anticoagulation when compared with therapeutic dosing in hospitalized COVID-19 patients. We searched PubMed, Google Scholar, EMBASE and COCHRANE databases from 2019 to 2021, without any restriction by language. We screened records, extracted data and assessed the risk of bias in the studies. RCTs that directly compare therapeutic and prophylactic anticoagulants dosing and are not placebo-controlled trials were included. Analyses of data were conducted using the Mantel-Haenszel random-effects model (DerSimonian-Laird analysis). The study is registered with PROSPERO (CRD42021265948). RESULTS: We included three studies in the final quantitative analysis. The incidence of thromboembolic events in therapeutic anticoagulation was lower in comparison with prophylactic anticoagulation in hospitalized COVID-19 patients and reached statistical significance [RR 1·45, 95% CI (1.07, 1.97) I2 -0%], whereas major bleeding as an adverse event was found lower in prophylactic anticoagulation in comparison with therapeutic anticoagulation that was statistically significant [RR 0·42, 95% CI(0.19, 0.93) I2 -0%]. CONCLUSION: Our study shows that therapeutic dose anticoagulation is more effective in preventing thromboembolic events than prophylactic dose but significantly increases the risk of major bleeding as an adverse event. So, the risk-benefit ratio must be considered while using either of them.

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response

A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.

Pregnancy with heart disease in South Asia: A systematic review and meta-analysis of prevalence and outcome.

Background: The prevalence and paradigm of antenatal heart disease are contrasting between high-income, industrialized, and low- and middle-income countries. In this systematic review, we report the prevalence of heart disease and its spectrum in pregnant women of South Asia. Methods: We searched through different electronic databases (PubMed, Google-scholar, Embase, Cochrane Library) to locate relevant articles. Studies with sufficient data that met our inclusion criteria were included. Two reviewers independently screened the articles. Discrepancies were resolved by other reviewers. Subsequently, data extraction was done using a standardized form and quality assessment of studies using the Joanna Briggs Institute tool. Meta-analysis was done using R software. Results: After various stages of screening 25 studies were included in the final quantitative synthesis. The pooled prevalence of heart disease among pregnant women was 1.46% (95% CI 0.99-2.01). Among those with heart disease, 70.25% (95% CI 64.87-75.38) had Rheumatic heart disease and 18.10% (95% CI 14.39-22.12) had congenital heart disease. The pooled prevalence of preterm labor and delivery among pregnant women with heart disease was 17.63% (95% CI 12.18-23.80). Similarly, the pooled maternal and fetal mortality rates were 26.14 (95% CI 12.47-43.55) and 50.48 (95% CI 29.59-75.83) per 1000 pregnant women with heart disease respectively. Conclusion: As pregnancy, itself is a prolonged state of physiologic stress, heart disease further adds to the risk both for the mother and fetus. Having such a high prevalence, efforts must be made to detect and closely monitor the condition antenatally, and decisions should be made according to the clinical conditions of the patient.

Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody

The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 g/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.

Endogenous endophthalmitis and multifocal brain abscess-An interesting case.

We present an unusual case that staphylococcal brain abscess can present in an immunocompetent with endogenous endophthalmitis secondary to a septic foci and early prevention of dissemination with appropriate management to prevent its complications.

SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil a-defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific a- and 8-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

India is one of the countries most affected by the recent COVID-19 pandemic. Characterization of humoral responses to SARS-CoV-2 infection, including immunoglobulin isotype usage, neutralizing activity and memory B cell generation, is necessary to provide critical insights on the formation of immune memory in Indian subjects. In this study, we evaluated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG, IgM, and IgA antibody responses, neutralization of live virus, and RBD-specific memory B cell responses in pre-pandemic healthy versus convalescent COVID-19 individuals from India. We observed substantial heterogeneity in the formation of humoral and B cell memory post COVID-19 recovery. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific IgG responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies. In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge. ImportanceOur study provides an understanding of SARS-CoV-2-specific neutralizing antibodies, binding antibodies and memory B cells in COVID-19 convalescent subjects from India. Our study highlights that PCR-confirmed convalescent COVID-19 individuals develop SARS-CoV-2 RBD-specific IgG antibodies, which correlate strongly with their neutralizing antibody titers. RBD-specific IgG titers, thus, can serve as a valuable surrogate measurement for neutralizing antibody responses. These finding have timely significance for selection of appropriate individuals as donors for plasma intervention strategies, as well as determining vaccine efficacy.

An Adaptive, Interacting, Cluster-Based Model Accurately Predicts the Transmission Dynamics of COVID-19

The SARS-CoV-2 driven disease, COVID-19, is presently a pandemic with increasing human and monetary costs. COVID-19 has put an unexpected and inordinate degree of pressure on healthcare systems of strong and fragile countries alike. In order to launch both containment and mitigation measures, each country requires accurate estimates of COVID-19 incidence as such preparedness allows agencies to plan efficient resource allocation and design control strategies. Here, we have developed a new adaptive, interacting, and cluster-based mathematical model to predict the granular trajectory COVID-19. We have analyzed incidence data from three currently afflicted countries of Italy, the United States of America, and India, and show that our approach predicts state-wise COVID-19 spread for each country with high accuracy. We show that R0 as the basic reproduction number exhibits significant spatial and temporal variation in these countries. However, by including a new function for temporal variation of R0 in an adaptive fashion, the predictive model provides highly reliable estimates of asymptomatic and undetected COVID-19 patients, both of which are key players in COVID-19 transmission. Our dynamic modeling approach can be applied widely and will provide a new fillip to infectious disease management strategies worldwide.

Lactobacillus pentosus Modulates Immune Response by Inducing IL-10 Producing Tr1 Cells

Several gut commensals have been shown to modulate host immune response. Recently, many food derived microbes have also been reported to affect the immune system. However, a mechanism to identify immunostimulatory and immunoregulatory microbes is needed. Here, we successfully established an in vitro screening system and identified an immunoregulatory bacterium, Lactobacillus pentosus KF340 (LP340), present in various fermented foods. LP340 induced a regulatory phenotype in mice Ag presenting cells which, in turn, induced IL-10 and IFN-γ producing Type 1 regulatory T cells (Tr1 cells) from naïve CD4⁺ T cells. Naïve CD4⁺ T cells co-cultured with LP340 treated dendritic cells highly expressed cytokine receptor IL-27R and were CD49b and lymphocyte-activation gene 3 double positive. Oral administration of LP340 in mice with atopic dermatitis reduced cellular infiltration in affected ear lobes and serum IgE levels, thus, ameliorating the disease symptoms. This suggests a systemic immunoregulatory effect of LP340. These findings demonstrate that LP340, a bacterium derived from food, prevents systemic inflammation through the induction of IL-10 producing Tr1 cells.

Association of genetic polymorphisms with plasma TFPI level: Boon or curse for DVT patients - Study from India.

Low plasma TFPI levels have been associated with an increased risk of DVT; however its association with TFPI gene polymorphisms is controversial and not yet studied in India. The aim of our study was to analyze prevalence of TFPI gene polymorphisms, evaluate their effects on its plasma levels and determine its association with DVT. Plasma level and genetic polymorphisms (33T>C, 399C>T and 536C>T) of TFPI were screened in subjects (100 DVT patients and 100 controls). Mean TFPI level in patients was significantly lower than controls (Patients: 33.55±11.72ng/ml, Controls: 48.05±13.68ng/ml, p<0.001). DVT patients had significantly higher prevalence of 399C>T (p=0.001, ORa: 5.69, CI: 1.14-28.46) and lower prevalence of 33T>C polymorphism (p<0.001, ORa: 0.239, CI: 0.065-0.871). The wild type (TT genotype) of 33T>C and variant form (CT and TT genotype) of 399C>T polymorphism was significantly associated with low TFPI levels. TFPI 536C>T polymorphism was absent in all subjects. In conclusion, dual nature of TFPI gene polymorphisms were established in our association study; 33T>C being protective and 399C>T as an important risk factor in Indian DVT patients, probably mediated by alteration in TFPI levels. These findings may prove a vital role in risk stratification and treatment of DVT.

Intravesical Migration of an Intrauterine Contraceptive Device with Secondary Calculus Formation / 가정의학회지

Intrauterine contraceptive devices (IUCDs) are a common form of reversible contraception owing to fewer systemic side effects and low cost, especially in a developing country like India. However, IUCDs are not without complications. Migration of a device into adjacent organs is the most morbid of all the documented complications. A patient who presents with a history that suggests loss or disappearance of an IUCD thread associated with urinary symptoms should raise suspicions that a device may have migrated into the bladder. Physicians should also be aware of possible secondary vesical calculus formation. Further radiological investigations and appropriate management are warranted. We present a case report describing the migration of an IUCD into the bladder with secondary calculus formation.