The Chest Pain That Never Went Away: A Case of Complex Cardiopulmonary Pathologies in a 64-Year-Old Caucasian Male.

Chest pain is a common and complex symptom that can arise from various etiologies, ranging from benign musculoskeletal conditions to life-threatening cardiovascular events. It is a hallmark symptom of myocardial infarction, angina, and other ischemic heart diseases, necessitating prompt and thorough evaluation. Ongoing chest pain post-procedures and medication administration presents a diagnostic challenge, as it may be indicative of an exacerbation of underlying conditions. We present the case of a 64-year-old Caucasian male who initially presented with severe and persistent chest pain suggestive of an anterior wall ST-elevation myocardial infarction (STEMI). He had a history of coronary artery disease and had recently undergone cardiac catheterization. Despite prompt administration of nitroglycerin and aspirin, the patient's symptoms persisted, prompting emergent percutaneous coronary intervention (PCI). Subsequent to PCI, ongoing chest discomfort persisted, prompting further investigation, which revealed a concurrent lung mass and nodules on imaging. Additional interventions, including repeated PCI procedures and thoracentesis, were undertaken. Unfortunately, the patient's clinical course rapidly deteriorated, culminating in cardiac arrest and unsuccessful resuscitative efforts. This case highlights the complexities inherent in managing intricate cardiovascular conditions and emphasizes the critical importance of maintaining vigilance for concomitant pathologies.

A Rare Case of Symptomatic Anomalous Origin of the Right Coronary Artery With a High Interarterial Course Between the Pulmonary Artery and the Aorta.

The congenital anomalous origin of the right coronary artery (AORCA) with an incongruous course is a rare malformation that can manifest as exertional chest pain, syncope, arrhythmias, heart failure, and sudden cardiac death. We present a case of a 42-year-old male with a history of hypercholesterolemia who presented with chest pain and dizziness upon exertion for two weeks. The physical examination was unremarkable, and the patient was hemodynamically stable. Initial blood tests were normal. Electrocardiogram (ECG) showed sinus bradycardia at 56 bpm without ST or T wave changes. A cardiac stress test indicated antero-apical inducible ischemia with a moderate probability of stress-induced ischemia. Computed tomography angiography (CTA) revealed an AORCA with a high interarterial course between the pulmonary artery and the aorta. Subsequent left heart catheterization confirmed the anomalous origin and revealed atherosclerotic disease. This anomaly was identified as the cause of the patient's symptoms due to the compression of the right coronary artery (RCA). The patient was treated with aspirin and statin and underwent successful internal mammary artery-RCA bypass grafting. Postoperatively, the patient's symptoms resolved, and there were no further episodes of chest pain.

Intracardiac Shunt Reversal and Early Right Ventricular Failure after Left Ventricular Assist Device Implantation.

Right ventricular failure (RVF) is a common complication that occurs after a left ventricular assist device (LVAD) is implanted. We report an interesting case of severe and refractory hypoxia during the early postoperative period after HeartMate3 (HM3) (Abbott Laboratories, Lake Forest, IL) implantation resulting in the unmasking of a right-to-left intracardiac shunt through a patent foramen ovale (PFO), triggered by early RVF. Importantly, the patient had a small left-to-right shunt after receiving a left-sided Impella 5.5 micro-axial pump (Abiomed, Danvers, MA, USA) pre-LVAD implantation. We observed improved hypoxia but worsening RVF after percutaneous PFO closure, necessitating right-sided mechanical circulatory support. We outline potential reasons for the significant PFO-related shunting seen after HM3 implantation, but not after Impella 5.5 placement. Uncertainty exists regarding the approach to a PFO in patients undergoing LVAD implantation. We propose an approach based on existing literature.

An Ambispective Community-Based Survival Study of Common Cancers in Rural Jodhpur, Rajasthan, Western India.

Background Cancer is the leading cause of death globally. Information on cancer patterns and survival is essential for the effective planning and implementation of cancer control interventions. Objective This study aimed to identify various factors associated with the survival estimates of common cancers. Methods A community-based ambispective study was conducted in a rural population. Data were collected from individuals diagnosed with cancer or relatives of individuals who died of cancer. The total population covered was 82,983. All cancer cases diagnosed since 2005 and followed until the year 2020 were included. Survival analysis and five-year survival rates were estimated. A Cox proportional hazard model was used. Results A total of 146 cancer patients were included in the study. Five-year survival estimates for breast cancer, head and neck cancer, and GI cancer were 72%, 28%, and 0%, respectively. The median survival time was lowest for GI cancers (1 year), and for head and neck and breast cancers, it was 3 and 6 years, respectively. Multivariate Cox regression was performed, adjusting for age, type of hospital, alcohol use, tobacco use, opium use, gender, treatment sought, GI cancer, frequency of changing hospitals, and frequency of follow-up. After adjustment, changing hospitals ≥3 times, being lost to follow-up, receiving no treatment, tobacco abuse, and the presence of GI cancers were significantly associated with survival estimates. Conclusions The five-year survival estimate for GI cancers was the lowest compared to other cancers. Study participants who were lost to follow-up or who took no treatment were significantly associated with lower survival estimates.

Gamma-Tubulin 1 (TUBG1) Mutation-Associated Lissencephaly and Microcephaly in an Indian Child: A Rare Case.

Malformations of cortical development (MCD) are a group of disorders affecting the normal development of the human cortex and are significant causes of delay in psychomotor development and epilepsy in children. Lissencephaly (smooth brain) forms a major group of brain malformations. Microtubules help in the migration of neuronal cells. Defect in tubulin gene alpha-tubulin (TUBA), beta-tubulin (TUBB), and gamma-tubulin (TUBG) leads to defective neuronal migration. This group of disorders is termed as "tubulinopathies." The important genes implicated in causing lissencephaly are LIS1, XLIS, and TUBA1A gene. Recently, a mutation in the TUBG1 gene is associated with it. Here, we report a one-and-a-half-year-old girl with global developmental delay, microcephaly, infantile-onset epilepsy, epileptic spasms, dysmorphism, and motor signs. There was no significant birth history. Neuroimaging (MRI) showed a broad thick gyri and a decreased number of sulci suggestive of lissencephaly/pachygyria spectrum. There was dilatation of the ventricles, and no grey matter heterotopia was noted. Sleep EEG showed multifocal epileptiform discharges. The child was treated with multiple anti-seizure medicines (ASMs). A genetic test, whole exome sequencing, was done to determine the etiology of MCD. A heterozygous missense variation in exon 6 of the TUBG1 gene was identified and reported as a "variant of unknown significance." Still, because the genotype matched with the clinical phenotype of the patient, it was considered clinically significant. Therefore, a complete diagnosis of TUBG1 mutation-associated cortical malformation (lissencephaly/pachygyria) with microcephaly and early-onset epilepsy was established. TUBG1 mutation is de novo in most cases, but parental testing is recommended. The parents of such patients need to be counseled about the need for prenatal testing and the risk of the disease to siblings. The overall prognosis in such cases is poor because of refractory seizures, physical limitations, and intellectual disability.

Prevalence and gender difference in depression in primary health care in India: A systematic review and meta-analysis.

Background: Depression contributes to the major burden of mental illness in India. Assessment of burden is essential to develop interventions to address the problem at the primary care level. Materials and Methods: We carried out a systematic review and meta-analysis of studies documenting the prevalence of depression in primary care in India. A wide literature search strategy was developed using keywords and Medical Subject Headings. The literature search was done in MEDLINE (via PubMed), IndMed, and major Indian psychiatric journal websites. The protocol was registered at PROSPERO. Bias assessment was carried out using a Cochrane risk of bias tool. Results: A total of 186 studies were identified after an initial search, of which 17 were included in the final analysis using pre-specified inclusion and exclusion criteria. The aggregate point prevalence of depression at the primary care level of the 17 studies using the random-effect model was 23.0% (95% CI: 16.0-30.0%). Significant heterogeneity was reported among the studies attributed majorly to a variety of study tools for assessing depression. Sub-group analysis revealed the higher aggregated prevalence of depression among females as compared to males at the primary care level. Conclusion: The study provided updated evidence of higher and gender differential burden of depression at the primary care level in India.

Unraveling HDAC11: Epigenetic orchestra in different diseases and structural insights for inhibitor design.

Histone deacetylase 11 (HDAC11), a member of the HDAC family, has emerged as a critical regulator in numerous physiological as well as pathological processes. Due to its diverse roles, HDAC11 has been a focal point of research in recent times. Different non-selective inhibitors are already approved, and research is going on to find selective HDAC11 inhibitors. The objective of this review is to comprehensively explore the role of HDAC11 as a pivotal regulator in a multitude of physiological and pathological processes. It aims to delve into the intricate details of HDAC11's structural and functional aspects, elucidating its molecular interactions and implications in different disease contexts. With a primary focus on elucidating the structure-activity relationships (SARs) of HDAC11 inhibitors, this review also aims to provide a holistic understanding of how its molecular architecture influences its inhibition. Additionally, by integrating both established knowledge and recent research, the review seeks to contribute novel insights into the potential therapeutic applications of HDAC11 inhibitors. Overall, the scope of this review spans from fundamental research elucidating the complexities of HDAC11 biology to the potential of targeting HDAC11 in therapeutic interventions.

Impact of supplementation with iron-folic acid (IFA) and vitamin D3 compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA).

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.

Long-Term Kinetics of SARS-CoV-2 Neutralizing and Anti-Receptor Binding Domain Antibodies among Laboratory-Confirmed COVID-19 Cases in Delhi National Capital Region, India: A Prospective, One-Year Follow-Up Study.

Background: This study was conducted with the objective of measuring the neutralizing and anti-receptor binding domain antibody levels against SARS-CoV-2 among laboratory-confirmed COVID-19 cases and exploring its long-term kinetics over a period of 1 year. Methods: One hundred laboratory-confirmed COVID-19 cases were recruited. Serum samples of the participants were collected within three months from the date of the positive COVID-19 report. The participants were prospectively followed up every three months for symptoms and the collection of blood samples for three additional rounds. The presence of anti-SARS-CoV-2 antibodies (IgA, IgG, and IgM antibodies), anti-receptor binding domain antibodies (anti-RBD), and neutralizing antibodies were measured. Findings: Median plaque reduction neutralization test (PRNT) titers showed a rising trend in the first three rounds of follow-up. The quantitative anti-receptor binding domain ELISA (QRBD) values showed a declining trend in the initial three rounds. However, both the PRNT titers and QRBD values showed significantly higher values for the fourth round of follow-up. Total antibody (WANTAI) levels showed an increasing trend in the initial three rounds (statistically significant). Interpretation: Neutralizing antibodies showed an increasing trend. The anti-receptor binding domain antibodies showed a decreasing trend. Neutralizing antibodies and anti-RBD antibodies persisted in the majority.

Prevalence and determinants of anemia due to micronutrient deficiencies among children aged 12-59 months in India-Evidence from Comprehensive National Nutrition Survey, 2016-18.

The present study aimed to estimate the prevalence of anemia, and anemia with micronutrient deficiencies (iron/ vitamin B12/ folic acid) and their determinants among children aged 12-59 months in India. Comprehensive National Nutritional Survey (2016-2018) is Asia's largest nutrition survey conducted among 0-19 years aged children in India. We used generalised linear model (modified Poisson) with adjusted prevalence ratio (aPR) to assess the socio-economic and biochemical factors associated with anemia and anemia with micronutrient deficiencies amongst children aged 12 to 59 months. Out of the total of 11,237 children included in the study, 40.5% (95%CI:38·6-42·6) were anemic, 30.0% (95%CI:27·8-32·4) had anemia with micronutrient deficiencies and 60.9% (95%CI:58·2-63·5) had micronutrient deficiencies with or without anemia. Younger age (aPR(95%CI) for one year old: 1.9(1.5-2.4), two year old: 1.8(1.5-2.2), three year old: 1.4(1.2-1.7) compared to four year old children) and lower educational status of the mother (mothers without formal schooling aPR(95%CI):1.4(1.1-1.8); 1-9 standards: 1.4(1.2-1.7)) vs mother educated with high school and above, consumption of less than 100 iron-folic acid tablets during pregnancy (aPR(95%CI):1.3(1.0-1.7) vs consumption of ≥ 180 tablets, any self-reported illness among children within two weeks preceding the interview (aPR(95%CI):1.2(1.1-1.4) vs no-illnesses, iron deficiency (aPR(95%CI):2.2(2.0-2.6)) and zinc deficiency (aPR(95%CI):1.3(1.1-1.4)) were associated with anemia in children. Among anemic, the children from scheduled tribe (aPR(95%CI):1.4(1.1-1.8)) vs other caste categories, and those following unsafe child faeces disposal practices (aPR(95%CI):1.2(1.0-1.4)) vs those who follow safe faeces disposal practices had higher chance of having micronutrient deficiency. One third of children aged 12-59 months had anemia with micronutrient deficiency (iron/ folic acid/ vitamin B12). More than half of children had micronutrient deficiencies irrespective of anemia. Micronutrient deficiencies, antenatal IFA intake, safe hygiene practices need to be strengthened to leave no stone unturned in control of anemia among under-five children in India.

Usage of older donors is associated with higher mortality after heart transplantation: A UNOS observational study.

BACKGROUND: Utilization of heart from older donors is variable across centers with uncertain outcomes of recipients. We sought to utilize a national registry to examine the usage and outcomes of heart transplant (HT) recipients from older donors. We also explored the impact of current donor heart allocation scheme on the outcomes of hearts from older donors. METHODS: This observational study utilized the United Network for Organ Sharing database between 2015 and 2023 with donors categorized into age <45 years or ≥45 years and evaluated organ disposition and geographical variation. Thirty-day, 1-, and 3-year mortality, and graft failure rates were compared among recipients as per donor age group. We also evaluated annual trends in HT for each group over the follow-up period. RESULTS: A total of 24,966 adult donors were recovered: 3,742 (15.0%) were ≥45 years; 3,349 (15.6%) adults received heart from such donors with significant geographical variation, and a declining utilization in the transplantation rate in current donor allocation system. Donors with age ≥45 years had higher comorbidities and were allotted with a significantly shorter ischemic time to recipients who were significantly less likely to receive temporary mechanical circulatory support and more likely female. Unadjusted and adjusted, 30-day mortality were similar but 1- and 3-year mortality and graft failure rates were significantly higher in recipients of such donors. Spline analysis suggested a higher 1-year mortality risk at older donor age with risk increasing after age 40 years. CONCLUSIONS: Older donor age was associated with worsened 1- and 3-year mortality and graft failure for heart transplant recipients.

Cell-Mediated Immunity (CMI) for SARS-CoV-2 Infection Among the General Population of North India: A Cross-Sectional Analysis From a Sub-sample of a Large Sero-Epidemiological Study.

Background Cell-mediated immunity (CMI), or specifically T-cell-mediated immunity, is proven to remain largely preserved against the variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including Omicron. The persistence of cell-mediated immune response in individuals longitudinally followed up for an extended period remains largely unelucidated. To address this, the current study was planned to study whether the effect of cell-mediated immunity persists after an extended period of convalescence or vaccination. Methods Whole blood specimens of 150 selected participants were collected and tested for Anti-SARS-CoV-2 Interferon-gamma (IFN-γ) response. Ex vivo SARS-CoV-2-specific interferon-gamma Enzyme-linked Immunospot (IFN-γ ELISpot) assay was carried out to determine the levels of virus-specific IFN-γ producing cells in individual samples. Findings Out of all the samples tested for anti-SARS-CoV-2 T-cell-mediated IFN-γ response, 78.4% of samples were positive. The median (interquartile range) spots forming units (SFU) per million levels of SARS-CoV-2-specific IFN-γ producing cells of the vaccinated and diagnosed participants was 336 (138-474) while those who were vaccinated but did not have the disease diagnosis was 18 (0-102); the difference between the groups was statistically significant. Since almost all the participants were vaccinated, a similar pattern of significance was observed when the diagnosed and the never-diagnosed participants were compared, irrespective of their vaccination status. Interpretations Cell-mediated immunity against SARS-CoV-2 persisted, irrespective of age and sex of the participant, for more than six months of previous exposure. Participants who had a history of diagnosed COVID-19 infection had better T-cell response compared to those who had never been diagnosed, in spite of being vaccinated.

Non-Lung Solid Organ Transplantation From SARS-CoV-2-Positive Donors to Uninfected Recipients.

BACKGROUND: There is a paucity of evidence on the risk of donor-recipient transmission of the SARS-CoV-2 in solid organ transplant recipients. Initial impressions suggest non-lung solid organs may be safely transplanted from SARS-CoV-2-positive donors without risk of viral transmission. METHODS: We reviewed clinical results of transplants in which SARS-CoV-2-negative recipients received non-lung solid organs from SARS-CoV-2-positive donors at a single transplant center. No prisoners were used in this study, and participants were neither coerced nor paid. The manuscript was created in compliance with the Helsinki Congress and the Declaration of Istanbul. RESULTS: Between June 2021 and January 2023, we transplanted 26 solid organs, including 13 kidneys, 8 livers, 3 hearts, and 1 simultaneous heart and kidney, from 23 SARS-CoV-2-positive donors into 25 SARS-CoV-2 negative recipients. Two of the recipients had a positive SARS-CoV-2 real-time polymerase chain reaction after transplantation, but otherwise, patients had no SARS-CoV-2-related complications, and all patients to date are alive with excellent allograft function. CONCLUSION: Transplantation of non-lung solid organs from SARS-CoV-2-positive donors into uninfected recipients can be safely performed without adverse effects from SARS-CoV-2.

A cross-sectional study on COVID-19 vaccine hesitancy in peri-urban areas in Kanpur, Uttar Pradesh, India.

Vaccination is a potential public health solution for the prevention of infection. It reduces the severity of symptoms in the case of COVID-19. Despite the availability of vaccines, some people are hesitant to be vaccinated. The objectives of this study were to measure the proportion of vaccine hesitancy among the peri-urban population and identify its determinants. An adult population of 303 from two peri-urban areas in the field practice area of the Urban Health Training Center, Rama Medical College, was interviewed from February 22 to March 25, 2021. Epicollect 5 was used for collecting data, and STATA 16 was used for analysis. Multivariable logistic regression was applied to compute the adjusted odds ratio (AOR) (95% confidence interval) to find out the determinants of vaccine hesitancy. The 3Cs model-guided tools were used for data collection and analysis. More than one-fourth (28%) of the participants were vaccine-hesitant, whereas 34.6% had no confidence in the vaccine. Other reasons were complacency (40.6%) and convenience (35.9%). Vaccine hesitancy was significantly associated with gender [AOR=2.40 (1.12-5.16)] and trust in government [AOR=0.18 (0.08-0.45)], but there was no association with age group, political affiliation, or source of information about the vaccine. It is important to build people's trust in vaccines, make them convenient, and resolve the issues that are making them complacent. The health system needs to involve non-governmental organizations to reach out to those for whom there are issues of availability and approach.

Assessment and management of allosensitization following heart transplant in adults.

Immunological injury to the allograft, specifically by antibodies to de novo donor specific human leukocyte antigen (dnDSA) and antibody mediated injury and rejection are the major limitations to graft survival after heart transplantation (HT). As such, our approach to allosensitization remains limited by the inability of contemporaneous immunoassays to unravel pathogenic potential of dnDSA. Additionally, the role of dnDSA is continuously evaluated with emerging methods to detect rejection. Moreover, the timing and frequency of dnDSA monitoring for early detection and risk mitigation as well as management of dnDSA remain challenging. A strategic approach to dnDSA employs diagnostic assays to determine relevant antibodies in conjunction with clinical presentation and injury/rejection of allograft to tailor therapeutics. In this review, we aim to outline contemporary knowledge involving detection, monitoring and management of dnDSA after HT. Subsequently, we propose a diagnostic and therapeutic approach that may mitigate morbidity and mortality while balancing adverse reactions from pharmacotherapy.

Detection and management of HLA sensitization in candidates for adult heart transplantation.

Heart transplantation (HT) remains the preferred therapy for patients with advanced heart failure. However, for sensitized HT candidates who have antibodies to human leukocyte antigens , finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting HT has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. This State-of-the-Art review discusses the assessment of human leukocyte antigens antibodies, potential desensitization strategies including mechanisms of action and specific protocols, the approach to a potential donor including the use of complement-dependent cytotoxicity, flow cytometry, and virtual crossmatches, and peritransplant induction management.