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Aswin Anand Pai, Ajith Mohan, Esther Sathya Bama Benjamin, Raveen Stephen Stallon Illangeswaran, Infencia Xavier Raj, Nancy Beryl Janet, Arun Kumar Arunachalam, ML Kavitha, Uday Kulkarni, Anup J Devasia, NA Fouzia, Aby Abraham, Alok Srivastava, Biju George, Vikram Mathews, Anu Korula, Poonkuzhali Balasubramanian Department of Haematology, Christian Medical College, Vellore, Tamilnadu, IndiaCorrespondence: Poonkuzhali BalasubramanianDepartment of Haematology, Christian Medical College, Vellore, Tamilnadu, IndiaEmail bpoonkuzhali@cmcvellore.ac.inPurpose: Severe myelosuppression in patients with acute lymphoblastic leukemia (ALL) undergoing 6-MP-based maintenance therapy is attributed to TPMT gene polymorphisms, which is rare in Asian populations. This study aims to evaluate the role of selected polymorphisms in NUDT15, ITPA, and MRP4 genes in addition to TPMT in predicting 6-MP intolerance during ALL maintenance therapy.Patients and Methods: We screened for the presence of NUDT15&ast;3 (c.415 C>T, rs116855232); MRP4 c.2269 C>T (rs3765534), ITPA c.94 C>A (rs1127354) polymorphisms in addition to TPMT &ast;2 (rs1800462), &ast;3A (&ast;3B and &ast;3C; rs1800460 and rs1142345) in ALL patients with documented severe neutropenia (cohort-1; n=42). These polymorphisms were then screened in a prospective cohort of ALL patients (cohort-2; n=133) and compared with 6-MP dose reduction, early/late myelotoxicity.Results: Nineteen (45%) patients in cohort-1 and 18 (14%) in cohort-2 had NUDT15 c.415 C>T variant while 4 (3%) patients in cohort-2 had TPMT&ast;3C variant. Five (12%) in cohort-1 and 30 (24%) in cohort-2 had ITPA c.94 C>A variant while 9 (22%) and 15 (12%) had MRP4 c.2269 C>T variant in cohorts-1 and 2, respectively. All in cohort-1 and 36 (27%) in cohort-2 had severe myelotoxicity. Twenty-eight patients (66.6%) in cohort-1 and 40 (30%) patients in cohort-2 had significant 6-MP dose reduction. NUDT15 c.415 C>T variant explained severe myelotoxicity in 63% and 33% in cohort 1 and 2. TPMT&ast;3C and ITPA c.94 C>A variants also explained myelotoxicity in cohort-2 (Median ANC: 376 vs 1014 mm3; p=0.04 and 776 vs 1023 mm3; p=0.04 respectively). NUDT15 c.415 C>T polymorphism explained significant myelotoxicity (507 vs 1298 mm3; p< 0.0001) in the multivariate analysis as well (β=− 0.314, p< 0.0001).Conclusion: NUDT15 c.415 C>T (15&ast;3), TPMT&ast;3C, as well as ITPA c.94 C>A and MRP4 c.2269 C>T polymorphisms explain hematotoxicities. Preemptive genotype-based (NUDT15&ast;3, TPMT, ITPA c.94 C>A) 6-MP dosing could improve the outcome after maintenance therapy.Keywords: leukemia, mercaptopurine, myelotoxicity, pharmacogenomics

The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003-2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15-48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54 and 21.21 in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06) required adjunctive procedures. Thirteen patients (17.8) had ≥ class 3 Clavien-Dindo complications and postoperative mortality occurred in 5 (6.8) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7, 45.2, and 15.1, respectively. Seven patients underwent metastasectomy. An 85 size reduction in the size of RPLN predicted necrosis. There was 71.4 concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range - 13.25-47.84). The 2-year recurrence-free survival (RFS) rate was 93 (95 confidence interval [CI]-83-97) and the overall survival (OS) rate was 90 (95 CI-80-95). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90 at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers., Author(s): Rakesh Kumar [1,2]; Madhuri Evangeline Sadanala [2]; Santosh Nagasubramanian [2]; Anjana Joel [3]; Arun Joseph Philip George [2]; S Mahasampath Gowri [4]; Partho Mukherjee [2]; Ashish Singh [3]; Rajiv [...]

Abstract Background The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available. Methods We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC). Results There were 936 patients aged 18–86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1–3% each. Conclusion The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS.

Background and Aim: Cardiogenic shock (CS) arising from ST-elevation myocardial infarction (STEMI) is associated with high mortality. This study aimed to evaluate the clinical characteristics and outcomes of early versus late-present patients with CS complicated with STEMI. Materials and Methods: This prospective observational study enrolled 92 patients with STEMI and CS from September 2020 to December 2021. Patients were divided into two groups based on the time from symptom onset to hospitalization: early (

Abstract The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various target antigens like B-cell membrane antigen (BCMA), G-protein-coupled receptor family C group 5 member D (GPRC5D), and Fc receptor-homolog 5 (FcRH5). These agents have proven to induce deep and durable responses in heavily pre-treated myeloma patients with a predictable safety profile and the ease of off-the-shelf availability. Significant research is ongoing to overcome resistance mechanisms like T cell exhaustion, target antigen mutation or loss and high disease burden. Various trials are also studying these agents as first line options in the newly diagnosed setting. These agents play an important role in the relapsed setting, and efforts are underway to optimize their sequencing in the myeloma treatment algorithm.

Introduction: One lung ventilation (OLV) is a technique used during lung resection surgery to facilitate optimal surgical conditions. However, this may result in severe hypoxemia due to the right-to-left shunt created in the collapsed lung. Several techniques are used to overcome hypoxemia, one of which is continuous positive airway pressure (CPAP) to the non-dependent lung. Another technique is ventilating the non-dependent lung with a minimal volume, thus creating differential lung ventilation (DLV) or split lung ventilation (SLV). In this study, we compared the efficacy of CPAP to DLV during video-assisted thoracoscopic (VATS) lung resection. Materials and Methods: In this single-center randomized controlled, cross-over study, each patient acted as his control as well as the study. Patients crossed over from SLV to CPAP (or vice versa) with an interval period during which only OLV was used (control period). The primary objective of the study was to observe the changes in oxygenation, ventilation, and the surgeons’ perception of the surgical field using CPAP or SLV to the non-ventilated lung during the period of OLV in patients undergoing thoracic surgery. Results: The study revealed that oxygenation was significantly better when using SLV to the non-ventilated lung during the period of OLV (P = 0.03). However, the surgeon found a significantly better surgical field when applying CPAP to the surgical field. Conclusions: The study showed that using SLV to the non-ventilated lung during the period of OLV was superior in terms of oxygenation, although it interfered more with the surgical field.

The aim of the present work was to examine the hydrocarbon degradation potential of yeasts isolated from the mangrove sediments. Mangrove sediments around the world were considered to be heavily polluted with oil contaminants and the microbes dwelling in them were believed to be highly active in metabolizing and detoxifying the oil fractions. In the present study, 70 yeast isolates were screened for their lipolytic activity qualitatively and 35 of them which showed comparatively higher lipolysis were tested for their crude oil degradation ability. Screening of hydro-carbon utilizing isolates was performed on Bushnell Haas agar media overlaid with 1% crude oil and the appearance of colonies were considered a positive. Three isolates were selected based on this and were sequenced using ITS gene of the 18S region of the rDNA and identified to be Candida tropicalis. The extent of crude oil degra-dation was assessed by growing the isolates in basal medium supplemented with heavy crude oil as the carbon source for 21 days. The residual crude oil fractions were then analyzed using GC-MS to quantitatively measure the degradation potential of each isolate. Our results showed that the yeast strains under study could actively metabolize the crude oil including the higher chain fractions which make them efficient hydrocarbon degraders that can be used in the bioremediation processes.

Gathering a diverse student body is important for institutions of higher education (IHEs) at the graduate/professional level. However, it is impossible to select a diverse student body from a homogenous group of candidates. Thus the aim of this study is to discover the extent to which diversity goals in admissions are precluded by the lack of diversity in the applicant pool. To explore this, the proportion of score reports sent to the 150 largest graduate/professional schools and sent for each major was compared, from each gender, race, and socioeconomic status (SES) grouping, to proportions from the overall applicant pool of graduate/professional students. Additionally, differences in the distance graduate/professional school applicants are willing to consider traveling by gender, race/ethnicity, and SES were investigated. Results show that differences exist in the gender, race, and SES distributions for score reports sent to different schools and for different majors as well as in the distance an applicant is willing to consider traveling for graduate/professional school. The patterns found for gender, racial, and socioeconomic diversity provide possibilities for researchers to work further together with graduate/professional schools to tackle the important challenge of increasing diversity in graduate/professional education.

This prospective study investigated the association between lipoprotein (a) [Lp(a)] levels and adverse cardiac events in patients undergoing percutaneous coronary intervention (PCI) for coronary artery disease. Among 600 patients, 79.16 % were male. Kaplan Meier analysis revealed significantly higher incidence rates of cardiac death, major adverse cardiac events, myocardial infarction, revascularization and stroke in patients with elevated Lp(a) (≥30 mg/dL). The Cox Regression model identified Lp(a) ≥30 mg/dL as a significant risk factor for adverse events (HR: 4.2920; 95%CI: 2.58–7.120; p

Introduction: Chemotherapy, postchemotherapy retroperitoneal lymph node dissection (pcRPLND), and metastasectomy remain the standard of care for the management of advanced nonseminomatous germ cell tumor (NSGCT). Methods: We retrospectively studied 73 patients who had pcRPLND at a single tertiary-care center (2003–2022). Surgical and clinicopathological features and oncological outcomes are presented. Results: The mean age was 28.27 years (15–48). Three-fourths had Stage III disease at diagnosis. International Germ Cell Cancer Collaborative Group risk stratification was 54.54% and 21.21% in intermediate risk, and poor risk, respectively. Sixty-two patients had Standard, 7 had Salvage and 4 underwent Desperation pcRPLND. Eleven patients (15.06%) required adjunctive procedures. Thirteen patients (17.8%) had ≥ class 3 Clavien–Dindo complications and postoperative mortality occurred in 5 (6.8%) patients. The histopathologies (HPE) of the pcRPLNDs were necrosis, teratoma, and viable tumor in 39.7%, 45.2%, and 15.1%, respectively. Seven patients underwent metastasectomy. An 85% size reduction in the size of RPLN predicted necrosis. There was 71.4% concordance between pcRPLND and metastasectomy HPEs. The median follow-up was 26.72 months (inter-quartile range – 13.25–47.84). The 2-year recurrence-free survival (RFS) rate was 93% (95% confidence interval [CI]–83%–97%) and the overall survival (OS) rate was 90% (95% CI–80%–95%). This is the largest series of pcRPLND for NSGCT in India to our knowledge. Conclusion: Although most of the cohort belonged to stage III, an RFS and OS rate of >90% at 2 years was achieved. We believe that successful management of postchemotherapy residual masses in NSGCT is contingent on the availability of multidisciplinary expertise and is therefore best done at tertiary-care referral centers.

Artificial Intelligence (AI) is revolutionizing many industries and becoming increasingly ubiquitous in everyday life. To empower children growing up with AI to navigate society's evolving sociotechnical context, we developed three middle school AI literacy curricula: "Creative AI,| "Dancing with AI," and "How to Train Your Robot." In this paper we discuss how we leveraged three design principles--active learning, embedded ethics, and low barriers to access -- to effectively engage students in learning to create and critique AI artifacts. During the summer of 2020, we recruited and trained in-service, middle school teachers from across the United States to co-instruct online workshops with students from their schools. In the workshops, a combination of hands-on unplugged and programming activities facilitated students' understanding of AI. As students explored technical concepts in tandem with ethical ones, they developed a critical lens to better grasp how AI systems work and how they impact society. We sought to meet the specified needs of students from a range of backgrounds by minimizing the prerequisite knowledge and technology resources students needed to participate. Finally, we conclude with lessons learned and design recommendations for future AI curricula, especially for K-12 in-person and virtual learning.

Background: Heart failure (HF) is a chronic and progressive condition that significantly impacts patients’ lives, necessitating a comprehensive understanding of the factors influencing their health outcomes. Among these factors, symptom perception, health-related quality of life (HRQoL), and predicted survival are paramount. This study aimed to assess symptom perception, HRQoL and predictive survival among HF patients. Methods: A baseline analysis was carried out in a randomized controlled trial involving patients with HF. Heart Failure Somatic Perception Scale to assess symptom perception, Kansas City Cardiomyopathy Questionnaire-12 to assess HRQoL and Seattle Heart Failure Model to assess predicted survival were used. Results: Among the 160 patients, 62.5 % were between 36 and 59 years of age and were married (88 %). Hypertension and diabetes were reported in 104 and 94 participants respectively, and among them, 65 participants had both hypertension and diabetes. The mean left ventricular ejection fraction was 33(%), and 56.5 % of the participants were in New York Heart Association functional class III and IV. The average symptom perception score was 27.4 ± 18.3, while the mean HRQoL score was 37.2 ± 14.2. The predicted one-year survival score was 80 ± 11.5, and the predicted five-year survival score was 38.5 ± 21.3. HRQoL showed a significant negative correlation with symptom perception (r = −0.75; p = 0.001) and a positive correlation with one-year survival (r = 0.53; p = 0.001), and five-year survival (r = 0.56; p = 0.001). Conclusion: Patients with HF experience persistent symptoms and poor HRQoL. Symptom severity decreases HRQoL. Understanding HRQoL and symptom perception is crucial for developing effective self-care interventions, which are vital for improving patient outcomes and managing HF effectively.

Abstract Meningioma is the most common benign primary brain tumour and does not usually metastasise. We report the case of a 69‐year‐old male patient with a history of meningioma who presented respiratory symptoms. He was found to have diffuse pleural metastasis from meningioma, which occurred 10 years after surgical management of recurrent meningioma. This case study provides insights into the clinical profile, workup and management of metastatic meningioma.

Introduction: Renal mesenchymal tumours are a subset of primary renal tumours arising from the mesenchymal tissue in the kidney. They are a heterogeneous group of mostly benign tumours that exhibit varied behaviours and molecular characteristics. Aim: To analyse the wide spectrum of histological subtypes, their unique clinical presentation, and pathological features of primary renal mesenchymal neoplasms. Materials and Methods: This was a retrospective cross- sectional observational clinicopathological study conducted in Department of General Pathology, Christian Medical College, tertiary care hospital, Vellore, Tamil Nadu, India, looking at data of adult Primary Renal Mesenchymal Tumours (PRMT) for a 15-year period between January 2006 and March 2021. Clinical details such as age, presenting symptoms, and tumour size were obtained from the hospital information system. Histopathology and immunohistochemical slides were reviewed for all the cases. Additional Immunohistochemistry (IHC) and molecular studies were performed for the undifferentiated sarcomas. The tumours were categorised into three groups as recommended by the World Health Organisation (WHO) 2020 classification of soft-tissue tumours based on biological behaviour: benign, intermediate, and malignant. Continuous variables are expressed as mean and Standard Deviation (SD). Comparison of categorical variables between groups was performed using the Chi-squared test. Continuous variables between groups were compared using the Student’s t-test for significance. A p-value of less than 0.05 was considered statistically significant. Results: Of the 2164 nephrectomies performed for neoplastic conditions, 97 (4.5%) were diagnosed as renal mesenchymal tumours. There were 59 (60.8%) benign, 10 (10.3%) with intermediate biologic behaviour and 28 (28.9%) malignant tumours. The mean ages at presentation were 40.5 years for benign, 43.4 years for intermediate, and 41 years for malignant tumours, respectively. Haematuria was seen in 11 of 38 (29%) intermediate grade and malignant tumours and in only 6 of 59 (10%) benign tumours, a difference that was statistically significant (p-value=0.017). Malignant tumours 24 of 28 (86%) were more likely to be larger (>7 cm) when compared to benign tumours 28 of 59 (47%) at the time of presentation (p-value=0.027). Classical angiomyolipomas constituted 53/59 (90%) of the benign tumours. Of the 10 intermediate grade tumours, epithelioid angiomyolipomas and solitary fibrous tumours were the most common, accounting for 50% and 30% of the intermediate group, respectively. Undifferentiated small round cell sarcoma was the most common malignant neoplasm, making up 12/28 (43%) of the malignant tumours. Conclusion: The present study found that renal mesenchymal tumours constitute a small but unique group of renal tumours. They are predominantly benign, but up to a quarter are malignant. Malignant tumours tend to be larger and more often present with haematuria. The present study highlights the importance of IHC in the diagnosis of intermediate and malignant mesenchymal tumours and the requirement of exhaustive molecular studies individually tailored to the immuno-profile of malignant tumours.

Background: Cardiovascular diseases (CVDs) are a leading cause of global mortality, motivating research into novel approaches for their management. Lipoprotein(a) (Lp(a)), a unique lipoprotein particle, has been implicated in atherosclerosis and thrombosis, suggesting its potential as a therapeutic target for CVDs. Aim: This study aimed to investigate the association of Lp(a) levels with various cardiovascular parameters and events among patients with confirmed cardiovascular disease. Methodology: A prospective study was conducted, enrolling 600 participants, predominantly comprising males (79%), with a mean age of 52.78 ± 0.412 years diagnosed with cardiovascular disease. The follow-up was done for 18 months. Patient demographics, blood investigations, and occurrence of major adverse cardiac events (MACE) were collected. SPSS version 21 was used to statistically analyze the relationships between elevated Lp(a) levels and factors such as age, glycated hemoglobin, mortality, MACE, cardiac death, target vessel revascularization, and stroke. Results: The study revealed significant (P < 0.05) associations between elevated Lp(a) levels and advanced age, increased glycated hemoglobin levels, as well as occurrences of all-cause mortality, MACE, cardiac death, target vessel revascularization, and stroke. Notably, a significant (P < 0.05), association between high Lp(a) levels and acute coronary syndrome (ACS) emerged, suggesting Lp(a)'s role in advanced cardiac events. Conclusion: The findings highlight the potential significance of Lp(a) as a notable risk factor in cardiovascular health. The observed associations between elevated Lp(a) and adverse cardiovascular events, including ACS, underscore its pathogenic role. Consequently, this study supports the rationale for further research into Lp(a)-specific therapeutic interventions, offering substantial promise in refining the management strategies for cardiovascular diseases.

The diagnosis of Multiple Myeloma (MM) is made by demonstration clonal plasma cells in Bone Marrow (BM) aspiration/biopsy, in addition to assessing serum biochemical parameters, conducting radiological examinations, and considering the clinical presentation. In most cases, predominantly mature plasma cells are observed, along with scattered immature forms in the BM. Several morphological variants of plasma cells have been reported, including Auer rod-like inclusions, small lymphocyte-like cells, hairy cell-like cells, anaplastic variants, promonocyte-like cells, crystal-storing histiocytes, Burkitt-like cells, and blastoid cells. In this series of five cases, most showed a typical clinical presentation and laboratory findings suggestive of plasma cell dyscrasia. However, the morphology of each case exhibited unusual morphological variants, posing diagnostic challenges. These variants included Auer rod-like inclusions, small lymphocytes/lymph-plasmacytoid cells, hairy-like cells, multilobulated nuclei, and anaplastic variants mimicking dysplastic megakaryocytes, leading to various differential diagnoses. The age range of these cases was 57-76 years. Most of the cases presented with generalised dull aching body pain. Imaging studies revealed lytic lesions involving various parts of the bone, including the skull, ribs, vertebrae, and femur. Biochemical assays suggested the possibility of plasma cell dyscrasia. Two of the cases had primary Plasma Cell Leukaemia (PCL), which is a rare and highly aggressive plasma cell neoplasm. The anaplastic variant is associated with a poor prognosis, aiding in predicting treatment responses. However, due to the unusual morphological presentation, the diagnosis of MM or PCL was made after conducting ancillary studies such as Serum Protein Electrophoresis (SPEP), serum free light chain assay, Immunofixation Electrophoresis (IFE), and immunophenotyping through Immunohistochemistry (IHC) or flow cytometry.

BACKGROUND: Heart failure (HF) is a chronic condition with significant public health concerns. HF necessitates adequate knowledge and adherence to self-care for enhanced quality of life and decreased rehospitalization. This study aimed to explore knowledge and self-care behavior in patients with HF. MATERIAL AND METHODS: The study was conducted in cardiology wards of a tertiary care hospital and the design was a randomized controlled trial. The baseline data (before the intervention) from 160 HF patients enrolled in a randomized controlled trial were analyzed. Knowledge and self-care behavior were measured using the Dutch HF Knowledge Questionnaire (score ranging from 0 to 15) and European HF Self-care Behavior Scale-9 (score ranging from 0 to 100). Higher scores indicated better self-care behavior and knowledge. Descriptive statistics such as frequency, percentage, mean, and standard deviation and inferential statistics such as independent sample t-test and ANOVA were performed. RESULTS: The majority (75.0%) were men with a mean age of 56.1 ± 7.9 years. A significant proportion had hypertension (65%), diabetes (58.7%), or both comorbidities (40.6%). Most exhibited a left ventricular ejection fraction

Abstract Endothelial dysfunction is a critical initiating factor contributing to cardiovascular diseases, involving the gut microbiome-derived metabolite trimethylamine N-oxide (TMAO). This study aims to clarify the time-dependent molecular pathways by which TMAO mediates endothelial dysfunction through transcriptomics and metabolomics analyses in human microvascular endothelial cells (HMEC-1). Cell viability and reactive oxygen species (ROS) generation were also evaluated. TMAO treatment for either 24H or 48H induces reduced cell viability and enhanced oxidative stress. Interestingly, the molecular signatures were distinct between the two time-points. Specifically, few Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were modulated after a short (24H) compared to a long (48H) treatment. However, the KEGG signalling pathways namely “tumour necrosis factor (TNF)” and “cytokine-cytokine receptor interaction” were downregulated at 24H but activated at 48H. In addition, at 48H, BPs linked to inflammatory phenotypes were activated (confirming KEGG results), while BPs linked to extracellular matrix (ECM) structural organisation, endothelial cell proliferation, and collagen metabolism were repressed. Lastly, metabolic profiling showed that arachidonic acid, prostaglandins, and palmitic acid were enriched at 48H. This study demonstrates that TMAO induces distinct time-dependent molecular signatures involving inflammation and remodelling pathways, while pathways such as oxidative stress are also modulated, but in a non-time-dependent manner.

Abstract Background The primary symptom of peripheral arterial disease (PAD) is intermittent claudication and the most common non-invasive diagnostic method is ankle brachial index. Peripheral arterial disease is usually accompanied by various other co-morbidities like type 2 diabetes mellitus, hypertension, and hypercholesterolemia. Literature suggests that when peripheral arterial disease is accompanied by type 2 diabetes mellitus, the ankle-brachial index can be falsely elevated due to medial calcification of the arteries. Therefore, an assessment of microcirculation using the toe brachial index is needed to diagnose PAD in these individuals. It has been well established that walking ability and ankle-brachial index are correlated in peripheral arterial disease. However, there is a dearth of literature on whether there is a correlation between toe brachial index (TBI) and walking ability. Therefore, the objective of the study is to find the correlation between toe brachial index and walking ability in type 2 diabetes mellitus with peripheral arterial disease. A total of 1485 participants were screened for the study, among which 133 met the inclusion criteria. Informed consent was obtained and the included participants were assessed for their demographic details. Toe brachial index was performed with the help of Doppler and 6-min walk test was performed to measure the claudication in the participants. Results In the present study of 133 participants, we found a strong positive correlation between toe brachial index and 6-min walk distance (r = 0.911 p value