Long-Term Outcomes of Heart Failure With Preserved or Mid-Range Ejection Fraction in the United States.

Background: Approximately one-half of all heart failure (HF) consists of heart failure with preserved ejection fraction (HFpEF) or heart failure with mid-range ejection fraction (HFmrEF). Although several recent trials have investigated treatments for HFpEF/HFmrEF, there is limited insight on the long-term clinical trajectory of this population. Objectives: The purpose of this study was to model clinical outcomes in patients with symptomatic (NYHA functional class II-IV) HFpEF/HFmrEF over 10 years. Methods: We developed a Markov model with stable HF, HF hospitalization, and death states to follow a cohort of patients with HFpEF/HFmrEF treated with standard of care (SoC) recommended by the American Heart Association/American College of Cardiology/Heart Failure Society of America. Population characteristics and clinical event probabilities were derived from recent phase 3 HFpEF/HFmrEF trials. We used weighted averages for control and sodium-glucose cotransporter-2 inhibitor outcomes. SoC was informed by baseline treatments reported in clinical trials. Results: In a cohort of U.S. patients with HFpEF/HFmrEF treated with SoC, our model estimated 0.53 cumulative HF hospitalizations per patient over 10 years. Overall, 37% had at least 1 HF hospitalization, and 26% experienced cardiovascular death. The model estimated 6.1 years of life expectancy from age 72 and total cost of care over this time of $123,900. Conclusions: HFpEF/HFmrEF is associated with high rates of HF hospitalization and cardiovascular mortality based on contemporary clinical trials in this population. Furthermore, clinical trial results are likely to be more optimistic than real-world outcomes. Continuing to optimize care and treatment may reduce clinical burden and improve population health.

Fetal Right Heart Strain in Systemic Right Ventricles and Impact on Post-surgical Outcomes.

Patients with hypoplastic left heart syndrome (HLHS) and its variants rely on the right ventricle (RV) to provide cardiac output. Diminished RV systolic function has been associated with poor clinical outcomes in this population. Echocardiographic strain has emerged as a useful method to quantify RV deformation. We aimed to describe fetal strain in the systemic RV and further investigate if there was any correlation with clinical outcomes. We conducted a retrospective, single center study evaluating strain in fetuses with systemic RV. We measured fetal RV global longitudinal strain (GLS) and segmental strain using Tomtec 2D speckle tracking software and compared these findings to controls. Fifty patients with systemic RV were included in the study group with controls matched one to one for each echocardiogram. Ten patients died after first-stage palliation. GLS was reproducible, with interobserver ICC 0.82. There was no statistically significant difference in GLS among different HLHS subtypes. Abnormal GLS did not correlate with worse clinical outcomes. GLS in systemic RVs in the 2nd and 3rd trimester did not vary significantly throughout gestation and did not correlate with clinical outcomes. Risk factors associated with poor outcome were mainly postnatal. Multi-centered studies are needed to determine if these findings hold true in a larger sample size.

Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer's disease.

Objectives: The aim of the present study was to study the potential therapeutic effects of quercetin in protection against repeated intranasal exposure of an amyloid-beta-induced mouse model. Methods: Mice received intranasal Aß1-42 (5 µg/10 µL) exposure once daily for seven consecutive days. Quercetin was orally administered to them at 30 mg kg-1 and 100 mg kg-1 doses for one week starting from day five following Aß1-42 peptide administration. Following this, the animals were evaluated for neurobehavioral parameters using a Morris water maze test and a novel object recognition test. Further to this, the biomarkers for neuroinflammation and neurodegeneration were evaluated in the hippocampus and cortex regions of the brain in these animals. Results: Multiple exposures to intranasal Aß led to a significant decline in the learning and cognitive memory of the animals, whereas oral treatment with quercetin at dosages of 30 and 100 mg kg-1 alleviated Aß-induced effects. Quercetin treatment significantly reduced Aß accumulation, oxidative stress and proinflammatory cytokine biomarkers in the brain. In addition, it also alleviated the activation of astrocytic biomarkers, amyloid precursor protein and phosphorylated-tau proteins in the brain. Conclusion: Quercetin was found to be a potent antioxidant, anti-inflammatory compound with protection against neurodegenerative damage and improved learning and cognitive memory in a repeated Aß-exposure model of AD.

Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.

Evaluating Carcinoembryonic Antigen and Glucose Levels in Pancreatic Cyst Fluid for Mucinous Versus Non-mucinous Differentiation.

BACKGROUND: A more precise identification of mucinous cysts will lower the likelihood of needless pancreatic surgery. Pancreatic cyst fluid (PCF) contains glucose and carcinoembryonic antigen (CEA), which serve as biomarkers to differentiate mucinous from non-mucinous pancreatic cystic neoplasms (PCNs). OBJECTIVE: To evaluate the diagnostic accuracy of combined CEA and glucose levels in PCF for distinguishing mucinous from non-mucinous PCNs preoperatively. METHODS: After receiving approval from the Institutional Ethical Committee of Indira Gandhi Institute of Medical Sciences, Patna, a cross-sectional validation research was carried out. All patients ≥18 years of age who had undergone pancreatic surgery or endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for a pancreatic cystic lesion and for whom PCF was acquired were eligible for inclusion. Patients were excluded if there was no PCF available, if they had been diagnosed with an extrapancreatic illness (such as ampullary adenoma), or if they could not be excluded due to pancreatic cancer generated from PCN. Diagnoses were pathologically confirmed. We performed measurements for CEA and glucose in PCF. CEA and glucose were measured using an Architect i2000SR analyzer (Abbott, Lake County, IL) and AU 5800 Beckman Coulter (Brea, CA), respectively. Diagnostic accuracy was evaluated by receiver operator characteristic (ROC) curves. RESULTS: PCF was obtained from 100 patients, of whom 54 (54%) had mucinous PCN and 46 (46%) had non-mucinous PCN. When CEA (cut-off ≥ 151 ng/ml) and glucose levels (cut-off ≤ 50 mg/dL) were combined, the results showed 46% sensitivity and 92% specificity. However, when CEA (cut-off ≥ 17 ng/ml) or glucose testing (cut-off ≤ 50 mg/dL) was used separately, the results showed 82% sensitivity and 73% specificity. CONCLUSION: The combined CEA and glucose testing in PCF demonstrated high specificity and sensitivity for differentiating mucinous from non-mucinous PCNs, suggesting its potential utility in preoperative diagnosis.

MK2 inhibitor PF-3644022 shows protective effect in mouse microglial N9 cell line induced with cigarette smoke extract.

Neuroinflammation is suggested as one of the potential links between CS-induced neuronal dysfunction. Cigarette smoke (CS) is one of the significant contributors of neuroinflammation, consequently leading to cognitive impairment and neurodegeneration. Microglia are the key resident macrophage cells in the brain with cell surface TLR4 receptor for responding to various stress signals. The CS constituents promote inflammation and oxidative stress in microglia leading to cytotoxicity through the TLR4-MK2 axis. However, the role of MK2 kinase in CS-induced microglial inflammation is not yet clearly understood. Therefore, we have used an MK2 inhibitor, PF-3644022 to study modulation of CS-extract induced oxidative and inflammatory signaling in a mouse microglial cell line, Furthermore, we also evaluated the enzymatic activity of acetylcholinesterase (AChE) on a direct exposure of enzyme with CS. CS exposure led to microglial cytotoxicity and enhanced the level of oxidative stress and proinflammatory cytokine release by microglial cells. The microglial cells pretreated with MK2 inhibitor, PF-3644022 significantly reduced the levels of oxidative stress markers, proinflammatory markers, and improved the level of antioxidant proteins in these cells. In addition, direct exposure of CS showed reduction in the enzymatic activity of AChE.

A comparative analysis of mycobacterial ribonucleases: Towards a therapeutic novel drug target.

Bacterial responses to continuously changing environments are addressed through modulation of gene expression at the level of transcription initiation, RNA processing and/or decay. Ribonucleases (RNases) are hydrolytic or phosphorolytic enzymes involved in a majority of RNA metabolism reactions. RNases play a crucial role in RNA degradation, either independently or in collaboration with various trans-acting regulatory factors. The genus Mycobacterium consists of five subgenera: Mycobacteroides, Mycolicibacterium, Mycobacterium, Mycolicibacter and Mycolicibacillus, which include 63 fully sequenced species (pathogenic/non-pathogenic) to date. These include 13 different RNases, among which 5 are exonucleases (RNase PH, PNPase, RNase D, nano-RNases and RNase AS) and 8 are endonucleases (RNase J, RNase H, RNase P, RNase III, RNase BN, RNase Z, RNase G and RNase E), although RNase J and RNase BN were later identified to have exoribonuclease functions also. Here, we provide a detailed comparative insight into the Escherichia coli and mycobacterial RNases with respect to their types, phylogeny, structure, function, regulation and mechanism of action, with the main emphasis on RNase E. Among these 13 different mycobacterial RNases, 10 are essential for cell survival and have diverse structures hence, they are promising drug targets. RNase E is also an essential endonuclease that is abundant in many bacteria, forms an RNA degradosome complex that controls central RNA processing/degradation and has a conserved 5' sensor domain/DNase-I like region in its RNase domain. The essential mycobacterial RNases especially RNase E provide a potential repertoire of drug targets that can be exploited for inhibitor/modulator screening against many deadly mycobacterial diseases.

Prevalence of Chronic Kidney Disease in Type 1 Diabetes Among Adults in the U.S.

OBJECTIVE: The prevalence of chronic kidney disease (CKD) in adults ≥18 years of age with type 1 diabetes in the U.S. was determined using National Health and Nutrition Examination Survey (NHANES) data. RESEARCH DESIGN AND METHODS: A modified treatment-based algorithm applying a subset of NHANES diabetes questionnaires was used. The number of respondents with CKD and type 1 diabetes was weighted (extrapolated) to the U.S. population. RESULTS: Based on data between 2015 and 2018, type 1 diabetes was identified in 47 out of 19,225 adults with evaluable kidney function data. CKD was present in 20 out of 47 people identified with type 1 diabetes. The weighted estimate of CKD in type 1 diabetes was 21.5%, corresponding to 258,196 (95% CI 71,189-445,203) people in the U.S. CONCLUSIONS: Applying a conservative approach in our study indicates that CKD is common in adults with type 1 diabetes in the U.S.

Antibacterial, Antifungal, and Cytotoxic Potential of PlumbaginLoaded pH-Responsive Vaginal Nanoformulations.

Plumbagin is a naphthoquinone from the roots of the Plumbago species and exhibits anticancer activity. Translational usage of plumbagin in biomedical sciences is restricted due to its poor solubility and bioavailability. Therefore, pH-responsive plumbagin-loaded vaginal nanoformulations with polylactic acid (PLA)-chitosan polymeric coat were fabricated by inotropic gelation technique. Among the four (F1, F2, F3, F4) nanoformulations prepared, F3 exhibited good interaction of polymers with plumbagin as evidenced by FTIR, XRD, and thermal analysis. The positive zeta potential (48.4 ± 5.57 mV), optimal size (694 ± 65.76 nm), low PDI (0.157), and good encapsulation efficiency (77.8 ± 3.62%) of F3 were significant. The indirect method of drug loading (58.35 ± 5.00%) confirmed the drug content of about 495.44 ± 5.00 µg of plumbagin in 1 mg of F3. The drug loading pattern was confirmed by TEM analysis, and the spherical morphology of the nanocomposite was confirmed by SEM analysis. F3 formulation showed 46% and 25.2% of drug release in 24 h in simulated vaginal fluid at pH 4.5 and 7 respectively with sustained release and hydrolyses of lactic acid from PLA. Among all the nanoformulations evaluated, nanoformulation F3 with promising physicochemical properties showed good antifungal and antibacterial activity against various fungal and bacterial strains. F3 exhibited potent cytotoxicity with an IC50 of 3.6 ± 0.12 µg/ml for HeLa and an IC50 of 0.81 ± 0.01 µg/ml for SiHa cells. Altogether, the nanoformulation F3 exhibited potent antimicrobial activity against vaginal infections and cytotoxicity against cervical cancer cell lines.

Discovering New QTNs and Candidate Genes Associated with Rice-Grain-Related Traits within a Collection of Northeast Core Set and Rice Landraces.

Grain-related traits are pivotal in rice cultivation, influencing yield and consumer preference. The complex inheritance of these traits, involving multiple alleles contributing to their expression, poses challenges in breeding. To address these challenges, a multi-locus genome-wide association study (ML-GWAS) utilizing 35,286 high-quality single-nucleotide polymorphisms (SNPs) was conducted. Our study utilized an association panel comprising 483 rice genotypes sourced from a northeast core set and a landraces set collected from various regions in India. Forty quantitative trait nucleotides (QTNs) were identified, associated with four grain-related traits: grain length (GL), grain width (GW), grain aroma (Aro), and length-width ratio (LWR). Notably, 16 QTNs were simultaneously identified using two ML-GWAS methods, distributed across multiple chromosomes. Nearly 258 genes were found near the 16 significant QTNs. Gene annotation study revealed that sixty of these genes exhibited elevated expression levels in specific tissues and were implicated in pathways influencing grain quality. Gene ontology (GO), trait ontology (TO), and enrichment analysis pinpointed 60 candidate genes (CGs) enriched in relevant GO terms. Among them, LOC_Os05g06470, LOC_Os06g06080, LOC_Os08g43470, and LOC_Os03g53110 were confirmed as key contributors to GL, GW, Aro, and LWR. Insights from QTNs and CGs illuminate rice trait regulation and genetic connections, offering potential targets for future studies.

Systems genomics of salinity stress response in rice.

Populations can adapt to stressful environments through changes in gene expression. However, the role of gene regulation in mediating stress response and adaptation remains largely unexplored. Here, we use an integrative field dataset obtained from 780 plants of Oryza sativa ssp. indica (rice) grown in a field experiment under normal or moderate salt stress conditions to examine selection and evolution of gene expression variation under salinity stress conditions. We find that salinity stress induces increased selective pressure on gene expression. Further, we show that trans-eQTLs rather than cis-eQTLs are primarily associated with rice's gene expression under salinity stress, potentially via a few master-regulators. Importantly, and contrary to the expectations, we find that cis-trans reinforcement is more common than cis-trans compensation which may be reflective of rice diversification subsequent to domestication. We further identify genetic fixation as the likely mechanism underlying this compensation/reinforcement. Additionally, we show that cis- and trans-eQTLs are under different selection regimes, giving us insights into the evolutionary dynamics of gene expression variation. By examining genomic, transcriptomic, and phenotypic variation across a rice population, we gain insights into the molecular and genetic landscape underlying adaptive salinity stress responses, which is relevant for other crops and other stresses.

In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia.

Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias. We report that proteomic analyses of immunoaffinity-purified lysates of primary AML cells showed enrichment of scaffolding protein IQGAP1. Immunohistochemistry and gene-expression analyses confirmed IQGAP1 mRNA overexpression in various cytogenetic subtypes of primary human AML compared to normal hematopoietic cells. shRNA knockdown of IQGAP1 blocked proliferation and clonogenicity of human leukemia cell-lines. To develop small molecules targeting IQGAP1 we performed in-silico screening of 212,966 compounds, selected 4 hits targeting the IQGAP1-GRD domain, and conducted SAR of the 'fittest hit' to identify UR778Br, a prototypical agent targeting IQGAP1. UR778Br inhibited proliferation, induced apoptosis, resulted in G2/M arrest, and inhibited colony formation by leukemia cell-lines and primary-AML while sparing normal marrow cells. UR778Br exhibited favorable ADME/T profiles and drug-likeness to treat AML. In summary, AML shows response to IQGAP1 inhibition, and UR778Br, identified through in-silico studies, selectively targeted AML cells while sparing normal marrow.

The role of RIPK1 in chronic obstructive pulmonary disease.

Necroptosis has emerged as one of the crucial pathological processes involved in the regulation of cell death and inflammation in chronic obstructive pulmonary disease (COPD). Airway epithelial necroptosis is closely linked to COPD pathogenesis. Necroptotic lung cells can release damage-associated molecular patterns (DAMPs) that can initiate a robust inflammatory response. However, the underlying mechanism of necroptosis in COPD is still not clearly understood. Therefore, we aimed to explore the roles and mechanisms of receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-mediated necroptosis in the regulation of inflammatory responses in COPD to provide insights into RIPK1-inhibitor drug discovery efforts and their therapeutic benefits in COPD.

Neoantigen Identification and Dendritic Cell-Based Vaccines for Lung Cancer Immunotherapy.

Immunotherapies can treat many cancers, including difficult-to-treat cases such as lung cancer. Due to its tolerability, long-lasting therapeutic responses, and efficacy in a wide spectrum of patients, immunotherapy can also help to treat lung cancer, which has few treatment choices. Tumor-specific antigens (TSAs) for cancer vaccinations and T-cell therapies are difficult to discover. Neoantigens (NeoAgs) from genetic mutations, irregular RNA splicing, protein changes, or viral genetic sequences in tumor cells provide a solution. NeoAgs, unlike TSAs, are non-self and can cause an immunological response. Next-generation sequencing (NGS) and bioinformatics can swiftly detect and forecast tumor-specific NeoAgs. Highly immunogenic NeoAgs provide personalized or generalized cancer immunotherapies. Dendritic cells (DCs), which originate and regulate T-cell responses, are widely studied potential immunotherapeutic therapies for lung cancer and other cancers. DC vaccines are stable, reliable, and safe in clinical trials. The purpose of this article is to evaluate the current status, limitations, and prospective clinical applications of DC vaccines, as well as the identification and selection of major histocompatibility complex (MHC) class I and II genes for NeoAgs. Our goal is to explain DC biology and activate DC manipulation to help researchers create extremely potent cancer vaccines for patients.

Continuous-Flow High-Pressure Homogenization of Blueberry Juice Enhances Anthocyanin and Ascorbic Acid Stability during Cold Storage.

Blueberries (Vaccinium section Cyanococcus) have a wealth of bioactive compounds, including anthocyanins and other antioxidants, that offer significant health benefits. Preserving these compounds and maintaining the sensory and nutritional qualities of blueberry products such as juice during cold market storage is critical to meet consumer expectations for nutritious, safe, and minimally processed food. In this study, we compared the effects of two preservation processing techniques, high-temperature short-time (HTST) and continuous flow high-pressure homogenization (CFHPH), on blueberry juice quality during storage at 4 °C. Our findings revealed that inlet temperature (Tin) of CFHPH processing at 4 °C favored anthocyanin retention, whereas Tin at 22 °C favored ascorbic acid retention. After 45 days of storage, CFHPH (300 MPa, 1.5 L/min, 4 °C) juice retained up to 54% more anthocyanins compared to control at 0 day. In contrast, HTST treatment (95 °C, 15 s) initially increased anthocyanin concentrations but led to their subsequent degradation over time, while also significantly degrading ascorbic acid. Furthermore, CFHPH (300 MPa, 4 °C) juice had significantly lower polyphenol oxidase activity (>80% less than control), contributing to the overall quality of the juice. This innovative processing technique has the potential to improve commercial blueberry juice, and help meet the rising demand for healthy and appealing food choices.

Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis.

INTRODUCTION: Common mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing the social determinants of mental health may represent a key strategy for effectively preventing CMHCs. However, no systematic reviews have evaluated the effectiveness of these combined intervention strategies for preventing CMHCs. METHODS AND ANALYSIS: This systematic review will include randomised controlled trials (RCTs) focused on the effectiveness of interventions that combine preventive psychological interventions with interventions that address the social determinants of mental health in LMICs. Primary outcome is the frequency of depression, anxiety or PTSD at postintervention as determined by a formal diagnostic tool or any other standardised criteria. We will search Epistemonikos, Cochrane Controlled Trials Register (CENTRAL), MEDLINE, Embase, PsycINFO, CINAHL, Global Index Medicus, ClinicalTrials.gov (Ctgov), International Clinical Trials Registry Platform (ICTRP). Two reviewers will independently extract the data and evaluate the risk of bias of included studies using the Cochrane risk of bias tool 2. Random-effects meta-analyses will be performed, and certainty of evidence will be rated using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: This study uses data from published studies; therefore, ethical review is not required. Findings will be presented in a published manuscript. TRIAL REGISTRATION NUMBER: CRD42023451072.

Lindane and Cetrimide lotion poisoning in an adult patient: A case report on an uncommon ingestion.

Lindane induces severe side effects, including fatality, while Cetrimide causes esophageal damage. With no antidotes available, our patient ingested both, requiring prompt gastric lavage and comprehensive treatment.

Comparative Study of Spinal, Epidural, and Sequential Combined Spinal Epidural Anesthesia in Geriatric Patients for Transurethral Resection of the Prostate.

BACKGROUND:  Sequential combined spinal epidural anesthesia (CSEA) is probably the greatest advancement in the central neuraxial block in this decade for geriatric patients due to the potential advantages of both spinal and epidural anesthesia. This study was designed to compare the clinical effects of sequential CSEA versus spinal and epidural anesthesia in geriatric patients undergoing transurethral resection of the prostate (TURP). METHODS:  Ninety patients aged 65 to 80 years were randomly allocated into three groups of 30 each. Group A (n=30) patients were administered spinal anesthesia with 2.5 ml of 0.5% hyperbaric bupivacaine, group B (n=30) received epidural anesthesia with 15 ml of 0.5% isobaric bupivacaine, and group C (n=30) received sequential CSEA with 1 ml of 0.5% hyperbaric bupivacaine and 6 ml of 0.5% isobaric bupivacaine given through epidural route to extend the block up to T10. Patients were observed for hemodynamic parameters, sensory and motor block, total dose required to establish the desired level, and patient satisfaction score. RESULTS: None of the patients were excluded in the study. Group A patients reported rapid onset of sensory block (3.08±11.57 minutes) compared to group B (11.57±1.48 minutes), and group C (5.47±1.25 minutes). The onset of motor block was expeditious in group A (8.08±1.0 minutes) compared to group B (20.33±1.86 minutes) and group C (15.53±1.31 minutes). Patients in group B had maximum hemodynamic stability but with delayed onset and were technically more complex than group A. Patients in group C were hemodynamically more stable than group A. They had a faster onset of action with decreased doses of local anesthetic drug required compared to group B. CONCLUSION: Sequential CSEA is a safe, effective, and reliable technique that combines the advantages of both spinal and epidural while minimizing their disadvantages. It has the advantage of stable hemodynamic parameters along with the provision of prolongation analgesia for geriatric patients undergoing TURP surgery.