Characterization of antibody-dependent cellular phagocytosis in patients infected with hepatitis C virus with different clinical outcomes.

Early neutralizing antibodies against hepatitis C virus (HCV) and CD8 + T cell effector responses can lead to viral clearance. However, these functions alone are not sufficient to protect patients against HCV infection, thus undefined additional antiviral immune mechanisms are required. In recent years, Fc-receptor-dependent antibody effector functions, particularly, antibody-dependent cellular phagocytosis (ADCP) were shown to offer immune protection against several RNA viruses. However, its development and clinical role in patients with HCV infection remain unknown. In this study, we found that patients with chronic GT1a or GT3a HCV infection had significantly higher concentrations of anti-envelope 2 (E2) antibodies, predominantly IgG1 subclass, than patients that cleared the viruses while the latter had antibodies with higher affinities. 97% of the patients with HCV had measurable ADCP of whom patients with chronic disease showed significantly higher ADCP than those who naturally cleared the virus. Epitope mapping studies showed that patients with antibodies that target antigenic domains on the HCV E2 protein that are known to associate with neutralization function are also strongly associated with ADCP, suggesting antibodies with overlapping/dual functions. Correlation studies showed that ADCP significantly correlated with plasma anti-E2 antibody levels and neutralization function regardless of clinical outcome and genotype of infecting virus, while a significant correlation between ADCP and affinity was only evident in patients that cleared the virus. These results suggest ADCP was mostly driven by antibody titer in patients with chronic disease while maintained in clearers due to the quality (affinity) of their anti-E2 antibodies despite having lower antibody titers.

Elevated BMI reduces the humoral response to SARS-CoV-2 infection.

Objective: Class III obesity (body mass index [BMI] ≥ 40 kg m-2) significantly impairs the immune response to SARS-CoV-2 vaccination. However, the effect of an elevated BMI (≥ 25 kg m-2) on humoral immunity to SARS-CoV-2 infection and COVID-19 vaccination remains unclear. Methods: We collected blood samples from people who recovered from SARS-CoV-2 infection approximately 3 and 13 months of post-infection (noting that these individuals were not exposed to SARS-CoV-2 or vaccinated in the interim). We also collected blood samples from people approximately 5 months of post-second dose COVID-19 vaccination (the majority of whom did not have a prior SARS-CoV-2 infection). We measured their humoral responses to SARS-CoV-2, grouping individuals based on a BMI greater or less than 25 kg m-2. Results: Here, we show that an increased BMI (≥ 25 kg m-2), when accounting for age and sex differences, is associated with reduced antibody responses after SARS-CoV-2 infection. At 3 months of post-infection, an elevated BMI was associated with reduced antibody titres. At 13 months of post-infection, an elevated BMI was associated with reduced antibody avidity and a reduced percentage of spike-positive B cells. In contrast, no significant association was noted between a BMI ≥ 25 kg m-2 and humoral immunity to SARS-CoV-2 at 5 months of post-secondary vaccination. Conclusions: Taken together, these data showed that elevated BMI is associated with an impaired humoral immune response to SARS-CoV-2 infection. The impairment of infection-induced immunity in individuals with a BMI ≥ 25 kg m-2 suggests an added impetus for vaccination rather than relying on infection-induced immunity.

Dynamics and durability of HIV-1 neutralization are determined by viral replication.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4+ T cell counts <200 µl-1, being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response.

Dengue virus infection during window period of consecutive outbreaks in Nepal and assessment of clinical parameters.

Nepal is an endemic country for dengue infection with rolling of every 3 year's clear cyclic outbreaks with exponential growth since 2019 outbreak and the virus gearing towards the non-foci temperate hill regions. However, the information regarding circulating serotype and genotype is not frequent. This research discusses on the clinical features, diagnosis, epidemiology, circulating serotype and genotype among 61 dengue suspected cases from different hospitals of Nepal during the window period 2017-2018 between the two outbreaks of 2016 and 2019. E-gene sequences from PCR positive samples were subjected to phylogenetic analysis under time to most recent common ancestor tree using Markov Chain Monte Carlo (MCMC) and BEAST v2.5.1. Both evolution and genotypes were determined based on the phylogenetic tree. Serotyping by Real-time PCR and Nested PCR showed the co-circulation of all the 3 serotypes of dengue in the year 2017 and only DENV-2 in 2018. Genotype V for DENV-1 and Cosmopolitan Genotype IVa for DENV-2 were detected. The detected Genotype V of DENV-1 in Terai was found close to Indian genotype while Cosmopolitan IVa of DENV-2 found spreading to geographically safe hilly region (now gripped to 9 districts) was close to South-East Asia. The genetic drift of DENV-2 is probably due to climate change and rapid viral evolution which could be a representative model for high altitude shift of the infection. Further, the increased primary infection indicates dengue venturing to new populations. Platelets count together with Aspartate transaminase and Aalanine transaminase could serve as important clinical markers to support clinical diagnosis. The study will support future dengue virology and epidemiology in Nepal.

Clinical outcomes and prognostic factors in triple-negative invasive lobular carcinoma of the breast.

PURPOSE: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. METHODS: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. RESULTS: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p < 0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p = 0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p < 0.001). CONCLUSION: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Clinical Outcomes and Prognostic Factors in Triple-Negative Invasive Lobular Carcinoma of the Breast.

Purpose: Triple-negative invasive lobular carcinoma (TN-ILC) of breast cancer is a rare disease and the clinical outcomes and prognostic factors are not well-defined. Methods: Women with stage I-III TN-ILC or triple-negative invasive ductal carcinoma (TN-IDC) of the breast undergoing mastectomy or breast-conserving surgery between 2010 and 2018 in the National Cancer Database were included. Kaplan-Meier curves and multivariate Cox proportional hazard regression were used to compare overall survival (OS) and evaluate prognostic factors. Multivariate logistic regression was performed to analyze the factors associated with pathological response to neoadjuvant chemotherapy. Results: The median age at diagnosis for women with TN-ILC was 67 years compared to 58 years in TN-IDC (p<0.001). There was no significant difference in the OS between TN-ILC and TN-IDC in multivariate analysis (HR 0.96, p=0.44). Black race and higher TNM stage were associated with worse OS, whereas receipt of chemotherapy or radiation was associated with better OS in TN-ILC. Among women with TN-ILC receiving neoadjuvant chemotherapy, the 5-year OS was 77.3% in women with a complete pathological response (pCR) compared to 39.8% in women without any response. The odds of achieving pCR following neoadjuvant chemotherapy were significantly lower in women with TN-ILC compared to TN-IDC (OR 0.53, p<0.001). Conclusion: Women with TN-ILC are older at diagnosis but have similar OS compared to TN-IDC after adjusting for tumor and demographic characteristics. Administration of chemotherapy was associated with improved OS in TN-ILC, but women with TN-ILC were less likely to achieve complete response to neoadjuvant therapy compared to TN-IDC.

Persistence of a Frameshifting Deletion in SARS-CoV-2 ORF7a for the Duration of a Major Outbreak.

Australia experienced widespread COVID-19 outbreaks from infection with the SARS-CoV-2 Delta variant between June 2021 and February 2022. A 17-nucleotide frameshift-inducing deletion in ORF7a rapidly became represented at the consensus level (Delta-ORF7aΔ17del) in most Australian outbreak cases. Studies from early in the COVID-19 pandemic suggest that frameshift-inducing deletions in ORF7a do not persist for long in the population; therefore, Delta-ORF7aΔ17del genomes should have disappeared early in the Australian outbreak. In this study, we conducted a retrospective analysis of global Delta genomes to characterise the dynamics of Delta-ORF7aΔ17del over time, determined the frequency of all ORF7a deletions worldwide, and compared global trends with those of the Australian Delta outbreak. We downloaded all GISAID clade GK Delta genomes and scanned them for deletions in ORF7a. For each deletion we identified, we characterised its frequency, the number of countries it was found in, and how long it persisted. Of the 4,018,216 Delta genomes identified globally, 134,751 (~3.35%) possessed an ORF7a deletion, and ORF7aΔ17del was the most common. ORF7aΔ17del was the sole deletion in 28,014 genomes, of which 27,912 (~99.6%) originated from the Australian outbreak. During the outbreak, ~87% of genomes were Delta-ORF7aΔ17del, and genomes with this deletion were sampled until the outbreak's end. These data demonstrate that, contrary to suggestions early in the COVID-19 pandemic, genomes with frameshifting deletions in ORF7a can persist over long time periods. We suggest that the proliferation of Delta-ORF7aΔ17del genomes was likely a chance founder effect. Nonetheless, the frequency of ORF7a deletions in SARS-CoV-2 genomes worldwide suggests they might have some benefit for virus transmission.

Multiple Orientia clusters and Th1-skewed chemokine profile: a cross-sectional study in patients with scrub typhus from Nepal.

OBJECTIVES: Scrub typhus is an emerging infectious disease in Asia caused by Orientia tsutsugamushi (Ot). From Nepal, only scant data on the genetic epidemiology of this agent is available, and determinants of immunoregulation are poorly understood. METHODS: Patients (n = 238) referred to the National Public Health Laboratory (Kathmandu, Nepal) from all over Nepal for suspected scrub typhus were enrolled upon positive immunoglobulin (Ig)M testing between July and October 2015. From Ot 16S and 47 kD polymerase chain reaction (PCR)-positive samples, the variable domain I of the 56 kD gene was sequenced and phylogenetically analyzed. T helper (Th) cell-associated cytokines (n = 13) and chemokines (n = 12) were quantified by multiplex bead arrays. RESULTS: In 93/238 (39.1%) IgM-positive samples, Ot DNA was detected by quantitative PCR. Phylogenetic analysis of 56 kD sequences revealed seven distinct clusters, six of them with high homologies to strains detected in other countries. The Th1-related cytokines interferon-γ and C-X-C motif chemokine ligand 10 were strongly upregulated and correlated with bacteremia, while levels of Th2-associated chemokines were reduced. Bacteremia also correlated with concentrations of interleukin (IL)-6 and IL-10 but not tumor necrosis factor-α. CONCLUSION: We identified a considerable genetic heterogeneity of human-pathogenic Ot strains circulating in Nepal. Acute Nepalese scrub typhus patients showed strong Th1 but impaired Th2 responses, especially on the chemokine level.

Epidemiology of dengue in SAARC territory: a systematic review and meta-analysis.

BACKGROUND: Dengue is one of the common arboviral infections and is a public health problem in South East Asia. The aim of this systematic review and meta-analysis was to evaluate the prevalence and distribution of dengue in SAARC (South Asian Association for Regional Cooperation) countries. METHODS: The PubMed, PubMed Central, Embase and Scopus databases were searched for relevant studies. Statistical analysis on data extracted from the selected studied was conducted using the Comprehensive Meta-Analysis Software (CMA) version 3 software package. Proportions were used to estimate the outcome with a 95% confidence interval (CI). RESULTS: Across all studies, among cases of suspected dengue, 30.7% were confirmed dengue cases (proportion: 0.307, 95% CI: 0.277-0.339). The seroprevalence of dengue immunoglobulin (Ig)G, IgM or both (IgM and IgG) antibodies and dengue NS1 antigen was 34.6, 34.2, 29.0 and 24.1%, respectively. Among the different strains of dengue, dengue virus (DENV) strains DENV-1, DENV-2, DENV-3 and DENV-4 accounted for 21.8, 41.2, 14.7 and 6.3% of cases, respectively. The prevalence of dengue fever, dengue hemorrhagic fever and dengue shock syndrome was 80.5, 18.2 and 1.5%, respectively. Fever was a commonly reported symptom, and thrombocytopenia was present in 44.7% of cases. Mortality was reported in 1.9% of dengue cases. CONCLUSIONS: Dengue is a common health problem in South East Asia with high seroprevalence. DENV-2 was found to be the most common strain causing infection, and most dengue cases were dengue fever. In addition, thrombocytopenia was reported in almost half of the dengue cases.

Longitudinal Characterization of Phagocytic and Neutralization Functions of Anti-Spike Antibodies in Plasma of Patients after Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

Phagocytic responses by effector cells to opsonized viruses have been recognized to play a key role in antiviral immunity. Limited data on coronavirus disease 2019 suggest that the role of Ab-dependent and -independent phagocytosis may contribute to the observed immunological and inflammatory responses; however, their development, duration, and role remain to be fully elucidated. In this study of 62 acute and convalescent patients, we found that patients with acute coronavirus disease 2019 can mount a phagocytic response to autologous plasma-opsonized Spike protein-coated microbeads as early as 10 d after symptom onset, while heat inactivation of this plasma caused 77-95% abrogation of the phagocytic response and preblocking of Fc receptors showed variable 18-60% inhibition. In convalescent patients, phagocytic response significantly correlated with anti-Spike IgG titers and older patients, while patients with severe disease had significantly higher phagocytosis and neutralization functions compared with patients with asymptomatic, mild, or moderate disease. A longitudinal subset of the convalescent patients over 12 mo showed an increase in plasma Ab affinity toward Spike Ag and preservation of phagocytic and neutralization functions, despite a decline in the anti-Spike IgG titers by >90%. Our data suggest that early phagocytosis is primarily driven by heat-liable components of the plasma, such as activated complements, while anti-Spike IgG titers account for the majority of observed phagocytosis at convalescence. Longitudinally, a significant increase in the affinity of the anti-Spike Abs was observed that correlated with the maintenance of both the phagocytic and neutralization functions, suggesting an improvement in the quality of the Abs.

Prevalence and Contributing Factors of Gender-based Violence in SAARC Territories from 2010 to 2020: A Systematic Review and Meta-analysis.

BACKGROUND: Gender-based violence is a key global concern due to the high prevalence and increased socio-economic burden for survivors. However, estimation of the prevalence of gender-based violence is difficult due to differences in study design and underreporting of abuse, especially in developing nations. Therefore, we conducted this study to estimate the prevalence of Gender-based violence among women living in the SAARC region. METHODS: The review protocol was registered in PROSPERO (CRD42020219577). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout the review. A thorough database search was conducted to identify studies done in the SAARC region. Title and abstract screening were done in Covidence, followed by a full-text review. Data were extracted and pooled for analysis using the inclusion and exclusion criteria. Subgroup analysis was done where possible. RESULTS: A total of 76 studies were included in the systematic review and metaanalysis. The community prevalence of domestic violence (DV) was 43.8% (95% CI, 35.1% - 52.9%), GBV prevalence was 34.9% (95% CI, 30.2% - 39.9%) and IPV prevalence was 39.8% (95% CI, 30.7% - 49.6%). GBV prevalence was highest in illiterate women [54.2% (95% CI, 46.8% - 61.5%)] and lowest among women with higher than secondary level education [23.1% (95% CI, 16.2% - 32.0%)]. The prevalence of GBV among women in pregnancy or postpartum period was 32.3% (95% CI, 25.1% - 40.4%, I2: 98.64), while among female sexual workers, the prevalence of Gender-based violence was 42.1% (95% CI, 28.1% - 57.5%, I2: 99.25). CONCLUSIONS: There is a high prevalence of Gender-based violence in the SAARC region. Higher socioeconomic status and educational status are protective factors for Gender-based violence. However, more studies using validated tools are needed to understand the true extent of the problem.

Effect of Age and Socioeconomic Factors in the Utilization of Chemotherapy in Acute Lymphoblastic Leukemia (ALL): A SEER Database Study of 16,196 Patients.

INTRODUCTION: The use of multiagent chemotherapy in acute lymphoblastic leukemia (ALL) has resulted in improvement in overall survival (OS), albeit to a different extent across various age groups. This large database study aims to assess the disparity in the utilization of chemotherapy in ALL in the real-world setting. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, patients with ALL diagnosis from 2006 to 2016 were identified. Baseline characteristics were compared between the groups who did vs. did not receive chemotherapy using χ2 test. Multivariable logistic regression was used to evaluate the association between various sociodemographic factors and the receipt of chemotherapy in the entire cohort and in different age groups. RESULTS: Out of 16,196 patients, 1258 patients (8%) did not receive chemotherapy. There was a steady increase in the number of patients who did not receive chemotherapy with advancing age: 2.5% (0-18 years), 5.2% (19-40 years), 9.3% (41-65 years), and 36.2% (>65 years). There was an upward trend in the receipt of chemotherapy in patients >65 years over the last decade. In multivariate analysis, the likelihood of receiving chemotherapy decreased with advancing age, single or widowed status, low income and educational status, and lack of insurance. Insurance status was an independent predictor of receipt of chemotherapy across each age category. CONCLUSION: A significant proportion of patients >65 years do not receive chemotherapy in the United States. Age, marital status, income, education, and insurance status contribute to the disparity in utilization of chemotherapy.

Participatory Approach to Develop Evidence-Based Clinical Ethics Guidelines for the Care of COVID-19 Patients: A Mixed Method Study From Nepal.

During health emergencies such as the COVID-19 pandemic, healthcare workers face numerous ethical challenges while catering to the needs of patients in healthcare settings. Although the data recapitulating high-income countries ethics frameworks are available, the challenges faced by clinicians in resource-limited settings of low- and middle-income countries are not discussed widely due to a lack of baseline data or evidence. The Nepali healthcare system, which is chronically understaffed and underequipped, was severely affected by the COVID-19 pandemic in its capacity to manage health services and resources for needy patients, leading to ethical dilemmas and challenges during clinical practice. This study aimed to develop a standard guideline that would address syndemic ethical dilemmas during clinical care of COVID-19 patients who are unable to afford standard-of-care. A mixed method study was conducted between February and June of 2021 in 12 government designated COVID-19 treatment hospitals in central Nepal. The draft guideline was discussed among the key stakeholders in the pandemic response in Nepal. The major ethical dilemmas confronted by the study participants (50 healthcare professionals providing patient care at COVID-19 treatment hospitals) could be grouped into five major pillars of ethical clinical practice: rational allocation of medical resources, updated treatment protocols that guide clinical decisions, standard-of-care regardless of patient's economic status, effective communication among stakeholders for prompt patient care, and external factors such as political and bureaucratic interference affecting ethical practice. This living clinical ethics guideline, which has been developed based on the local evidence and case stories of frontline responders, is expected to inform the policymakers as well as the decision-makers positioned at the concerned government units. These ethics guidelines could be endorsed with revisions by the concerned regulatory authorities for the use during consequent waves of COVID-19 and other epidemics that may occur in the future. Other countries affected by the pandemic could conduct similar studies to explore ethical practices in the local clinical and public health context.

Aspergillosis: An Unwanted Tenant of Lung Cavity in an Immunocompromised Host.

Immunocompromised status predisposes an individual to infection from bacteria, fungi, and viruses that are otherwise uncommon. The presence of carcinoma and the use of chemotherapy weakens one's immune system and leads to opportunistic infections of many kinds. Aspergilloma is a fungal ball that grows inside a primary cavitary lesion within the pulmonary parenchyma. Generally, immunocompromised individuals have severe and invasive infections from Aspergillus. Here, we present a case report of a female with breast carcinoma undergoing chemotherapy who previously had a lung abscess with Klebsiella. During her subsequent presentation, she was detected to have aspergilloma along with multi-drug-resistant organisms in the lung abscess along with metastasis of breast carcinoma and lung squamous cell carcinoma encapsulating the fungal ball.

Urgent Endoscopic Retrograde Cholangiopancreatography (ERCP) vs. Conventional Approach in Acute Biliary Pancreatitis Without Cholangitis: An Updated Systematic Review and Meta-Analysis.

Gallstone disease is the common cause of acute pancreatitis. The role of early endoscopic retrograde cholangiopancreatography (ERCP) in biliary pancreatitis without cholangitis is not well-established. Thus, this study aims to compare the outcome of early ERCP with conservative management in patients with acute biliary pancreatitis without acute cholangitis. An online search of PubMed, PubMed Central, Embase, Scopus, and Clinicaltrials.gov databases was performed for relevant studies published till December 15, 2020. Statistical analysis was performed using RevMan v 5.4 (The Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen). Odds Ratio (OR) with a 95% confidence interval was used for outcome estimation. Among 2700 studies from the database search, we included four studies in the final analysis. Pooling of data showed no significant reduction in mortality (OR 0.59, 95% CI 0.32 to 1.09; p=0.09); overall complications (OR 0.56, 95% CI 0.30 to 1.01; p=0.05); new-onset organ failure (OR 1.06, 95% CI 0.65 to 1.75; p=0.81); pancreatic necrosis (OR 0.80, 95% CI 0.49 to 1.32; p=0.38); pancreatic pseudo-cyst (OR 0.44, 95% CI 0.16 to 1.24; p=0.12); ICU admission (OR 1.64, 95% CI 0.97 to 2.77; p=0.06); and pneumonia development (OR 0.81, 95% CI 0.40 to 1.65; p=0.56) by urgent ERCP comparing with conventional approach for acute biliary pancreatitis without cholangitis. Henceforth, early ERCP in acute biliary pancreatitis without cholangitis did not reduce mortality, complications, and other adverse outcomes compared to the conservative treatment.

Hypothermia versus normothermia after out-of-hospital cardiac arrest: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The current guidelines recommend targeted temperature management (TTM) as part of the post-resuscitation care for comatose patients following out-of-hospital cardiac arrest. These recommendations are based on the weak evidence of benefit seen in the early clinical trials. Recent large multicentered trials have failed to show a meaningful clinical benefit of hypothermia, unlike the earlier studies. Thus, to fully appraise the available data, we sought to perform this systematic review and meta-analysis of randomized controlled trials. METHODS: We searched four databases for randomized controlled trials comparing therapeutic hypothermia (32-34 °C) with normothermia (≥36 °C with control of fever) in adult patients resuscitated after out-of-hospital cardiac arrest. Independent reviewers did the title and abstract screening, full-text screening, and extraction. The primary outcome was mortality six months after cardiac arrest, and secondary outcomes were neurological outcomes and adverse effects. RELEVANCE FOR PATIENTS: Six randomized controlled trials were included in this review. There was no significant difference between the hypothermia and normothermia groups in mortality till 6 months follow up after out-of-hospital cardiac arrest (OR 0.88, 95% CI 0.67-1.16; n = 3243; I2 = 51%), or favorable neurological outcome (OR 1.31, 95% CI 0.93-1.84; n = 3091; I2 = 68%). Rates of arrhythmias were notably higher in the hypothermia group than the normothermia group (OR 1.43, 95% CI 1.20-1.71; n = 3029; I2 = 4%). However, odds for development of pneumonia showed no significant differences across two groups (OR 1.13, 95% CI 0.98-1.31; n = 3056; I2 = 22%). Therefore, targeted hypothermia with a target temperature of 32-34 °C does not provide mortality benefit or better neurological outcome in patients resuscitated after the out-of-hospital cardiac arrest when compared with normothermia.

Team-Based Learning Among Health Care Professionals: A Systematic Review.

Introduced in the 1970s to meet the academic needs of a growing number of students with relatively stagnant faculty, team-based learning (TBL) has revolutionized the modern classroom structure. Contrary to the traditional didactic model where the teacher assumes the central role and students are passive listeners, TBL participants are actively involved in the learning process. Teachers act as facilitators while the TBL participants work in groups to solve problems through engagement with their peers. The objective of the article is to conduct a systematic review on team-based learning using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The studies were searched in databases like PubMed®, Scopus®, Embase®, and PubMed Central® using appropriate keywords. Two authors screened the papers, and a third author resolved the conflicts. This was followed by a bibliographic review based on the references of the selected study and bias assessment using the Joanna Briggs Institute (JBI) critical appraisal tool. The team-based learning model is increasingly being used by different institutions globally. TBL and traditional lecture-based teaching outcomes revealed that TBL participants performed better in academic, clinical, and communication domains. In addition, TBL enhanced learners' engagement, collaborative spirit, and satisfaction. Our study results are similar to the prior meta-analysis and systematic review. Nevertheless, this systematic review remains more comprehensive, up-to-date, and inclusive thus far. Team-based learning is a pragmatic and superior approach to learning among health care professionals. It has resulted in better academic, clinical, and communication outcomes. This finding spans all the medical and allied professions studied in this systematic review.

Maintenance of broad neutralizing antibodies and memory B cells 1 year post-infection is predicted by SARS-CoV-2-specific CD4+ T cell responses.

Understanding the long-term maintenance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity is critical for predicting protection against reinfection. In an age- and gender-matched cohort of 24 participants, the association of disease severity and early immune responses on the maintenance of humoral immunity 12 months post-infection is examined. All severely affected participants maintain a stable subset of SARS-CoV-2 receptor-binding domain (RBD)-specific memory B cells (MBCs) and good neutralizing antibody breadth against the majority of the variants of concern, including the Delta variant. Modeling these immune responses against vaccine efficacy data indicate a 45%-76% protection against symptomatic infection (variant dependent). Overall, these findings indicate durable humoral responses in most participants after infection, reasonable protection against reinfection, and implicate baseline antigen-specific CD4+ T cell responses as a predictor of maintenance of antibody neutralization breadth and RBD-specific MBC levels at 12 months post-infection.

Improving Medical Education: A Narrative Review.

With the advancement in basic and clinical sciences, medical education is also constantly evolving. The Accreditation Council for Graduate Medical Education (ACGME) has endorsed six core competencies to improve teaching and learning. This narrative review was conducted after searching the article databases (PubMed, PubMed Central, Embase, and Scopus) about the core competencies such as medical knowledge (problem-based learning), interpersonal communication, patient care, professionalism, practice-based learning and improvement, and system-based care endorsed by ACGME. We included randomized and quasi-experimental trials, cohorts, and case-control studies in this narrative review. In a problem-based learning modality, a real-life scenario is allocated to a group of students. Studies have shown that it is more effectively demonstrated by a better post-test score, improved concentration, and application of knowledge. Interpersonal communication skills promote collaboration with interdisciplinary teams, work quality, and patient adherence to treatment. Professionalism is a human attribute that creates a pleasant work environment and is an essential trait that improves patients' adherence to treatment. In system-based care, patients are benefitted through a well-structured plan of care. Finally, in practice-based learning, medical trainees learn to systematically evaluate the pattern of care and practice the best modality to improve the overall patient care and physician satisfaction. These core competencies need to be incorporated into all levels of medical training.