Prescription Patterns in Management of Heart Failure and Its Association With Readmissions: A Retrospective Analysis.

BACKGROUND: The American Heart Association/American College of Cardiology/Heart Failure Society of America recently added sodium-glucose cotransporter-2 inhibitors in addition to renin-angiotensin-aldosterone system inhibitors, beta-blockers, and mineralocorticoid receptor antagonists to form the 4 pillars of guideline-directed medical therapy (GDMT) for the management of heart failure with reduced ejection fraction (HFrEF). Despite strong evidence suggesting improved outcomes with inpatient initiation of GDMT at target doses, significant lag has been noted in prescription practices. We sought to study GDMT prescription rates in patients with HFrEF at the time of hospital discharge and evaluate its association with various patient characteristics and all-cause readmission rates. METHODS AND RESULTS: We used a modified version of Heart Failure Collaboratory (HFC) score to characterize patients into 2 groups (those with an HFC score of <3 and an HFC score of ≥3) and to examine various socioeconomic and biomedical factors affecting GDMT prescription practices. Out of the eligible patients, the prescription rates for beta-blockers was 77.9%, renin-angiotensin-aldosterone system inhibitor was 70.3%, and mineralocorticoid receptor antagonists was 41%. Furthermore, prescription rates for sacubitril/valsartan was 27.7% and sodium-glucose cotransporter-2 inhibitors was 17%. Only 1% of patients had an HFC score of 9 (drugs from all 4 classes at target doses). Patients of black ethnicity, those admitted on teaching service and those with HFrEF as the primary cause of admission were more likely to have an HFC of ≥3 at discharge. An HFC of ≥3 was associated with lower rates of 1-month all-cause readmissions. CONCLUSIONS: Consistent with the prior research, our data show significant gaps in prescription of GDMT in HFrEF. Further implementation research should be done to improve GDMT prescription during inpatient stay.

Oncological Outcomes of Sub-Lobar Resection Versus Lobectomy for Stage I Non-Small Cell Lung Cancer.

INTRODUCTION: Although lobectomy has been the treatment of choice for early-stage non-small cell lung cancer (NSCLC), sub-lobar resection (i.e., segmentectomy or wedge resection) has emerged as an alternative over time due to its ability to preserve additional lung function. This meta-analysis explores the survival outcomes of sub-lobar resection versus lobectomy in patients with stage I NSCLC (tumor size: ≤2 cm). MATERIAL AND METHODS: We conducted a systematic search of PubMed, EMBASE, and the Cochrane Library from inception up to July 28, 2023. The hazard ratios and odds ratios for overall survival (OS), disease-free survival (DFS), and mortality were calculated using the random effects model. RESULTS: A total of 27 studies, comprising 10,449 patients, were included. Sub-lobar resection demonstrated comparable OS and DFS to that of lobectomy. Similarly, there was no significant risk of mortality associated with any of the groups. However, the subgroup analysis according to patient selection (intentional, compromised, not specified, and both [intentional and compromised]) showed that the patients in the compromised subgroup had a poor DFS with sub-lobar resection as compared to lobectomy (hazard ratio: 1.52, confidence interval: 1.14-2.02, P = 0.004). Additionally, there was no significant difference in OS, DFS, or overall mortality in the results stratified by surgical procedure or patient selection. CONCLUSIONS: The patients with stage I NSCLC who underwent sub-lobar resection showed a significantly worse DFS and OS in the "compromised group." However, there was no overall significant difference in OS, DFS, or mortality in the sub-lobar resection group as compared to lobectomy.

Endoplasmic reticulum's role in multiple sclerosis, exploring potential biomarkers, and pioneering therapeutic strategies: a comprehensive review of literature.

BACKGROUD: Multiple Sclerosis (MS) is a complex and chronic autoimmune disease that affects the central nervous system. Inflammation and demyelination characterize it, which results in a range of neurological impairments. The increasing worldwide occurrence of MS, affecting an estimated 2.8 million individuals in 2020, highlights the urgent requirement for further research to tackle the significant impact it has on individuals and healthcare systems globally. OBJECTIVE: In this study, we wanted to explore the complex function of the endoplasmic reticulum (ER) in the origin, development, and resolution of MS, emphasizing its importance in neuroinflammatory illnesses. The ER has become a central focus in comprehending the pathogenesis of MS. Upon reviewing the literature, we observed a lack of thorough analysis that explores the involvement of endoplasmic reticulum stress in multiple sclerosis. Thus, we aimed through this research to examine the correlations between ER stress and its influence on immunological dysregulation, demyelination, and neurodegeneration in MS. FINDINGS: Based on the latest clinical trials, we suggested theories that explore possible biomarkers linked to ER stress and the unfolded protein response. Identifying molecules that are suggestive of early stages of illness and can serve as prognostic tools for improving our understanding of the heterogeneity of MS and offering novel approaches for managing the disease. Finally, through our comprehensive search, we wanted to offer a plan for future research, suggesting new and creative methods for managing MS and encouraging the creation of specific treatments that aim to reduce the impact of MS on individuals worldwide.

Temporal trends and regional variations in mortality related to Guillain-Barré syndrome in the United States: a retrospective study from 1999 to 2020.

AIM: Guillain-Barré syndrome (GBS) is an autoimmune neurological disorder, with an estimated 6.4% increase in cases worldwide from 1990 to 2019. We aim to identify the GBS-related mortality trends in the US stratified by age, sex, race, and region. METHODS: We used data from the CDC-WONDER database to calculate crude (CMR) and age-adjusted mortality rates (AAMRs) per 1,000,000 people. We examined the temporal trends through annual percent change (APC) and the average annual percent change (AAPC) in rates using Joinpoint regression. RESULTS: From 1999 to 2020, a total of 10,097 GBS-related deaths occurred in the US. The AAMR decreased till 2014 (APC: -1.91) but increased back to initial levels by 2020 (APC: 3.77). AAMR was higher in males (1.7) than females (1.1), decreasing till 2015 for females and 2014 for males, but increasing thereafter only for females. Non-Hispanic (NH) American Indians or Alaska Natives displayed the highest AAMR (1.8) while NH Asians or Pacific Islanders displayed the lowest (0.6). AAMRs also varied by region (West: 1.5; South: 1.5; Midwest: 1.4; Northeast: 1.1). Rural regions exhibited a higher AAMR (1.7) than urban regions (1.3). Most deaths occurred in medical facilities (60.99%). The adults aged ≥85 years exhibited an alarmingly high CMR (14.0). CONCLUSIONS: While the mortality rates for GBS initially declined till 2014, they climbed back up afterwards. Highest mortality was exhibited by males and NH American Indians or Alaska Natives, residents of rural regions, and adults ≥85 years. Equitable efforts are needed to reduce the burden on high-risk populations.

Identification and Characterization of the DOF Gene Family in Phoebe bournei and Its Role in Abiotic Stress-Drought, Heat and Light Stress.

Phoebe bournei is a second-class endangered and protected species unique to China, and it holds significant ecological and economic value. DNA binding one zinc finger (Dof) transcription factors are plant-specific regulators. Numerous studies have demonstrated that Dof genes are involved in plant growth, development and responses to abiotic stress. In this study, we identified and analyzed 34 PbDof gene members at the whole-genome level. The results indicated that the 34 PbDof genes were unevenly distributed across 12 chromosomes. We utilized the Dof genes from Arabidopsis thaliana and P. bournei to construct a phylogenetic tree and categorized these genes into eight subgroups. In the collinearity analysis, there were 16 homologous gene pairs between AtDof and PbDof and nine homologous gene pairs between ZmDof and PbDof. We conducted a cis-acting element analysis and found that cis-acting elements involved in light response were the most abundant in PbDof genes. Through SSR site prediction, we analyzed that the evolution level of Dof genes is low. Additionally, we assessed the expression profiles of eight PbDof genes under high temperature, drought, and light stress using qRT-PCR. In particular, PbDof08 and PbDof16 are significantly upregulated under the three stresses. This study provides foundational information for PbDof genes and offers new insights for further research on the mechanism of Dof transcription factors responding to stress, as well as the adaptation of P. bournei to environmental changes.

Genomic Insights into and In Vitro Evaluation of Antimicrobial Combination Therapies for Carbapenem-Resistant Acinetobacter baumannii.

Background and Objectives: Acinetobacter baumannii (A. baumannii), particularly carbapenem-resistant A. baumannii (CRAB), represents a grave concern in healthcare settings and is associated with high mortality. This study aimed to conduct molecular, mutational, and phylogenetic analyses of specific genes in CRAB and evaluate the synergistic effects of selected antimicrobial combinations. Materials and Methods: Phenotypic characterization was performed on six CRAB strains by using the Modified Hodge Test (MHT) and IMP-EDTA Double-Disc Synergy Test (IMP-EDTA DDST). Carbapenemase- and metallo-beta-lactamase-encoding genes were amplified by using Polymerase Chain Reaction. Phylogenetic analysis using the MEGA 11 tool was used to determine the evolutionary relatedness of these genes. Mutational analysis was performed by using I-Mutant, MUPro, and PHD-SNP bioinformatics tools to predict mutations in the carbapenemase-encoding genes. Microdilution checkerboard titration assessed the synergistic effects of antimicrobial combinations (azithromycin-meropenem, rifampicin-meropenem, meropenem-colistin, and azithromycin-colistin) on these CRAB isolates. Results: The phenotypic characterization of six CRAB isolates revealed positive results for MHT and IMP-EDTA DDST. The molecular characterization revealed that carbapenemase- and MBL-encoding genes were present in all isolates with varying frequencies, including blaOXA-51 (100%) and blaIMP (0%). The sequence analysis revealed high evolutionary relatedness to sequences in the NCBI database. The mutational analysis identified 16 mutations, of which 1 mutation (P116L) in the blaOXA-58 gene predicted a change in the protein product, potentially contributing to carbapenem resistance. The checkerboard titration method did not reveal any synergism among the tested antimicrobial combinations against CRAB. Conclusion: This study's findings underscore the significant challenges posed by CRAB isolates harboring multiple resistant genes in treatment. This highlights the urgent need for novel antimicrobial agents, a crucial step towards reducing mortality rates not only in Pakistan but also globally.

An Exploratory Qualitative Analysis of the Stanford-Templeton Convenings on Islam and Suicide.

For over 70 years, studies have reported lower rates of completed suicide in Muslim-majority countries and individuals who identify as Muslim. To this point, the mechanisms underlying the relationship between Islam and lower risk of suicide remain understudied. In an effort to advance our understanding, we convened a bilingual international interdisciplinary panel of experts for a discussion of the current state and future directions of the field. In this paper, we present an exploratory qualitative analysis of the core themes that emerged from the group interviews. We also derive a general theoretical model of the association between Islam and suicide risk.

Comprehensive insights into the regulatory mechanisms of lncRNA in alkaline-salt stress tolerance in rice.

BACKGROUND: Alkaline-salt is one of the abiotic stresses that slows plant growth and developmental processes and threatens crop yield. Long non-coding RNAs (lncRNAs) are endogenous RNA found in plants that engage in a variety of cellular functions and stress responses. METHOD: lncRNAs act as competing endogenous RNAs (ceRNA) and constitute a new set of gene control. The precise regulatory mechanism by which lncRNAs function as ceRNAs in response to alkaline-salt stress remains unclear. We identified alkaline-salt responsive lncRNAs using transcriptome-wide analysis of two varieties including alkaline-salt tolerant [WD20342 (WD)] and alkaline-salt sensitive [Caidao (CD)] rice cultivar under control and alkaline-salt stress treated [WD20342 (WDT, and Caidao (CDT)] conditions. RESULTS: Investigating the competitive relationships between mRNAs and lncRNAs, we next built a ceRNA network involving lncRNAs based on the ceRNA hypothesis. Expression profiles revealed that a total of 65, 34, and 1549 differentially expressed (DE) lncRNAs, miRNAs, and mRNAs were identified in alkaline-salt tolerant WD (Control) vs. WDT (Treated). Similarly, 75 DE-lncRNAs, 34 DE-miRNAs, and 1725 DE-mRNAs (including up-regulated and down-regulated) were identified in alkaline-salt sensitive CD (Control) vs. CDT (Treated), respectively. An alkaline-salt stress ceRNA network discovered 321 lncRNA-miRNA-mRNA triplets in CD and CDT, with 32 lncRNAs, 121 miRNAs, and 111 mRNAs. Likewise, 217 lncRNA-miRNA-mRNA triplets in WD and WDT revealed the NONOSAT000455-osa_miR5809b-LOC_Os11g01210 triplet with the highest degree as a hub node with the most significant positive correlation in alkaline-salt stress response. CONCLUSION: The results of our investigation indicate that osa-miR5809b is dysregulated and plays a part in regulating the defense response of rice against alkaline-salt stress. Our study highlights the regulatory functions of lncRNAs acting as ceRNAs in the mechanisms underlying alkaline-salt resistance in rice.

Role of the type-B authentic response regulator gene family in fragrant rice under alkaline salt stress.

Globally, rice is being consumed as a main staple food and faces different kinds of biotic and abiotic stresses such drought, salinity, and pest attacks. Through the cytokinin signaling, Type-B authentic response regulators (ARR-Bs) respond positively towards the environmental stimuli. ARR-Bs are involved in abiotic stress tolerance and plant development but their molecular mechanisms in fragrant rice are still not fully explored. The current study showed the genome-wide characterization of OsARR-B genes under alkaline salt stress. Results showed that in total, 24 OsARR-B genes were found and divided into four subgroups on the basis of a phylogenetic analysis. These genes were located on all rice chromosomes except 8 and 10. Analysis of gene duplications, gene structure, cis-elements, protein-protein interactions, and miRNA were performed. Gene ontology analysis showed that OsARR-B genes are involved in plant development through the regulation of molecular functions, biological processes, and cellular components. Furthermore, 117 and 192 RNA editing sites were detected in chloroplast and mitochondrial genes, respectively, encoding proteins of OsARR-B. In chloroplast and mitochondrial genes, six and nine types of amino acid changes, respectively, were caused by RNA editing, showing that RNA editing has a role in the alkaline salt stress tolerance in fragrant rice. We also used a comparative transcriptome approach to study the gene expression changes in alkaline tolerant and susceptible genotypes. Under alkaline salt stress, OsARR-B5, OsARR-B7, OsARR-B9, OsARR-B10, OsARR-B16, OsARR-B22, and OsARR-B23 showed higher transcript levels in alkaline salt tolerant genotypes as compared to susceptible ones. Quantitative RT-PCR showed upregulation of gene expression in the alkaline tolerant genotypes under alkaline stress. Our study explored the gene expression profiling and RESs of two rice contrasting genotypes, which will help to understand the molecular mechanisms of alkaline salt tolerance in fragrant rice.

Adoption of circular economy for food waste management in the context of a developing country.

Food wastage is a global concern with high economic, social and environmental impacts. Pakistan, a developing country, is also significantly affected by the adverse impacts of food wastage. For overcoming this problem, the transition from a Linear to a Circular Economy (CE) for the management of food wastage can serve as a viable strategy. However, there are barriers of political, technical and cultural nature, which are impediments in the path of this transition. This study aims to identify and prioritize these barriers in order of their significance. This research study evaluated and ranked these barriers using a Fuzzy Multi-Criteria Decision Making (MCDM) technique, the Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS). A total of 15 barriers were analyzed, and the 'complicated intrinsic nature of CE', 'misleading information about shelf-life leading to waste rather than distribution', 'the poor economic viability of start-ups with CE model', 'corporate and organizational hesitance to change/innovate' and 'technological backwardness of farmers/growers on the agricultural production side' were ranked as the most significant hurdles. The novelty of this study lies in its application. This study is unique as it has focused on developing countries and proposed policy recommendations for the transition towards a CE. In light of the above-mentioned results, this study provides policy recommendations for public and private sector policymakers that would facilitate the food industry in shifting towards the CE model.

Optimization of CNN through Novel Training Strategy for Visual Classification Problems.

The convolution neural network (CNN) has achieved state-of-the-art performance in many computer vision applications e.g., classification, recognition, detection, etc. However, the global optimization of CNN training is still a problem. Fast classification and training play a key role in the development of the CNN. We hypothesize that the smoother and optimized the training of a CNN goes, the more efficient the end result becomes. Therefore, in this paper, we implement a modified resilient backpropagation (MRPROP) algorithm to improve the convergence and efficiency of CNN training. Particularly, a tolerant band is introduced to avoid network overtraining, which is incorporated with the global best concept for weight updating criteria to allow the training algorithm of the CNN to optimize its weights more swiftly and precisely. For comparison, we present and analyze four different training algorithms for CNN along with MRPROP, i.e., resilient backpropagation (RPROP), Levenberg-Marquardt (LM), conjugate gradient (CG), and gradient descent with momentum (GDM). Experimental results showcase the merit of the proposed approach on a public face and skin dataset.

Performance Optimization of Priority Assisted CSMA/CA Mechanism of 802.15.6 under Saturation Regime.

Due to the recent development in the field of Wireless Sensor Networks (WSNs), the Wireless Body Area Networks (WBANs) have become a major area of interest for the developers and researchers. Human body exhibits postural mobility due to which distance variation occurs and the status of connections amongst sensors change time to time. One of the major requirements of WBAN is to prolong the network lifetime without compromising on other performance measures, i.e., delay, throughput and bandwidth efficiency. Node prioritization is one of the possible solutions to obtain optimum performance in WBAN. IEEE 802.15.6 CSMA/CA standard splits the nodes with different user priorities based on Contention Window (CW) size. Smaller CW size is assigned to higher priority nodes. This standard helps to reduce delay, however, it is not energy efficient. In this paper, we propose a hybrid node prioritization scheme based on IEEE 802.15.6 CSMA/CA to reduce energy consumption and maximize network lifetime. In this scheme, optimum performance is achieved by node prioritization based on CW size as well as power in respective user priority. Our proposed scheme reduces the average back off time for channel access due to CW based prioritization. Additionally, power based prioritization for a respective user priority helps to minimize required number of retransmissions. Furthermore, we also compare our scheme with IEEE 802.15.6 CSMA/CA standard (CW assisted node prioritization) and power assisted node prioritization under postural mobility in WBAN. Mathematical expressions are derived to determine the accurate analytical model for throughput, delay, bandwidth efficiency, energy consumption and life time for each node prioritization scheme. With the intention of analytical model validation, we have performed the simulations in OMNET++/MIXIM framework. Analytical and simulation results show that our proposed hybrid node prioritization scheme outperforms other node prioritization schemes in terms of average network delay, average throughput, average bandwidth efficiency and network lifetime.

Mathematical modelling and deep learning algorithms to automate assessment of single and digitally multiplexed immunohistochemical stains in tumoural stroma.

Whilst automated analysis of immunostains in pathology research has focused predominantly on the epithelial compartment, automated analysis of stains in the stromal compartment is challenging and therefore requires time-consuming pathological input and guidance to adjust to tissue morphometry as perceived by pathologists. This study aimed to develop a robust method to automate stromal stain analyses using 2 of the commonest stromal stains (SMA and desmin) employed in clinical pathology practice as examples. An effective computational method capable of automatically assessing and quantifying tumour-associated stromal stains was developed and applied on cores of colorectal cancer tissue microarrays. The methodology combines both mathematical models and deep learning techniques with the former requiring no training data and the latter as many inputs as possible. The novel mathematical model was used to produce a digital double marker overlay allowing for fast automated digital multiplex analysis of stromal stains. The results show that deep learning methodologies in combination with mathematical modelling allow for an accurate means of quantifying stromal stains whilst also opening up new possibilities of digital multiplex analyses.

The Efficacy of Tafolecimab in Chinese Patients with Hypercholesterolemia: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels. METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I2 index. The risk of bias was assessed using Cochrane's RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020). RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, p value < 0.00001, I2 = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I2 = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I2 = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool. CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations. REGISTRATION: PROSPERO identifier number CRD42023471020.

Efficacy and safety of bedaquiline containing regimens in patients of drug-resistant tuberculosis: An updated systematic review and meta-analysis.

Background: Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis and leads to serious complications if left untreated. Some strains of Mycobacterium tuberculosis are multi-drug resistant and require treatment with newer drugs. Bedaquiline based treatment regimens have been used in patients who are diagnosed with drug resistant tuberculosis. The aim of this study is to assess the efficacy and safety profile of bedaquiline-based treatment regimens using a systematic review of existing literature and meta-analysis. Methods: In this study, an electronic search was carried out on PubMed, ScienceDirect, and Cochrane library to find relevant literature from March 2021 onwards. Random-effects model was used to assess pooled treatment success rate and 95 % CIs. p-value of <0.05 was suggestive of publication bias. The review is registered with PROSPERO: CRD42023432748. Results: A total of 543 articles were retrieved by database searching, out of which 12 new studies met the inclusion criteria. The total number of articles included in the review was 41 including 36 observational studies (having a total of 9,934 patients) and 5 experimental studies (having a total of 468 patients). The pooled treatment success rate was 76.9 % (95 % CI, 72.9-80.4) in the observational studies and 81.7 % (95 % CI, 67.2-90.7) in the experimental studies. Further subgroup analysis was done on the basis of treatment regimens containing bedaquiline only and treatment regimens containing bedaquiline and delamanid. The pooled treatment success rate in the studies consisting of patients who were treated with regimens containing bedaquiline only was 78.4 % (95 % CI, 74.2-82.1) and 73.6 % (95 % CI, 64.6-81.0) in studies consisting of patients who were treated with regimens containing bedaquiline and delamanid. There was no evidence of publication bias. Conclusions: In patients of drug resistant tuberculosis having highly resistant strains of Mycobacterium tuberculosis undergoing treatment with bedaquiline-based regimen demonstrate high rates of culture conversion and treatment success. Moreover, the safety profile of bedaquiline-based regimens is well-established in all studies.

Cardiac autonomic plexus neuromodulation for decompensated heart failure: An updated review on the positive inotropic technique based on the DRI2P2S classification.

Current pharmacological regimen is unable to improve adverse outcomes such as mortality post hospitalization for Acutely Decompensated Heart Failure (ADHF) patients. Ongoing research is directed towards managing ADHF patients with Cardiac Autonomic Nervous System (CANS) excitatory interventions having long-term prognosis benefits. Recently, a novel treatment coined as Cardiac Pulmonary Nerve Stimulation (CPNS) has reproducibly shown increased inotropy with no change in heart rate. However, there are some potential limitations associated with the neurostimulation of the parasympathetic component of the CANS plexus. The INOVATE-HF trial involved the vagus nerve only. The early termination of the INOVATE-HF trial gave valuable insights into the cardio-protective effect of simultaneously stimulating the sympathetic and parasympathetic components of the CANS plexus done in CPNS. It is essential to individualize the treatment protocol keeping in mind patient selection. Ongoing trials assessing the efficacy and safety of the CPNS technique in ADHF patients shall set the tone for such innovative techniques in times to come.

Efficacy and safety of norepinephrine versus phenylephrine for post-spinal hypotension in preeclamptic patients: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis to evaluate the fetomaternal outcomes after the administration of norepinephrine or phenylephrine for the treatment of post spinal hypotension in preeclamptic women undergoing a cesarean section. DATA SOURCES: We searched on PubMed, Embase, Scopus, Cochrane CENTRAL, and clinicaltrials.gov from inception till June 2024. STUDY SELECTION: Randomized controlled trials of preeclamptic women receiving norepinephrine or phenylephrine for post spinal hypotension were included. DATA EXTRACTION AND SYNTHESIS: Two reviewers extracted data onto an Excel spreadsheet. R version 4.4 was used for statistical analysis. Risk ratios (RR) and their 95% confidence intervals (CIs) were calculated and pooled using the random effects model. Cochrane's risk of bias (RoB 2) tool was used for quality assessment. This review has been registered with PROSPERO (CRD42024532740). RESULTS: A total of 4 trials, comprising 413 participants, were included in this review. 206 patients received norepinephrine, while 207 received phenylephrine. The incidence of maternal bradycardia was significantly lower in the norepinephrine group compared with the phenylephrine group (RR = 0.25, 95 % CI = 0.16 to 0.39, p < 0.01). There were no statistical differences in other maternal outcomes or in the umbilical artery and umbilical vein blood gas analysis values. We also analyzed adverse events such as nausea (RR = 1.00, 95 % CI: 0.62 to 1.60, p = 1.00) and vomiting (RR = 0.99, 95 % CI: 0.89 to 1.11, p = 0.61), but they did not show a significant association with any group. All the trials had a moderate or low risk of bias. CONCLUSION: Bolus doses of NE and PE for the treatment of post-spinal hypotension in preeclamptic women undergoing cesarean sections were found to exhibit comparable neonatal outcomes. However, NE provided superior maternal safety due to a lower incidence of bradycardia compared to PE.

Bevacizumab Combination Therapy Versus Standard Chemotherapy for Ovarian Cancer in Shorter and Longer Follow-Up Duration: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer over a shorter and longer follow-up period. METHODS: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% CIs. We assessed the quality of the included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). RESULTS: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had a low risk of bias, while 5 had some concerns. Bevacizumab was associated with a progression free survival benefit for <36 months (HR: 0.59, 95% CI: 0.45-0.76, P <0.0001, I2 =90%) and >36 months (HR: 0.66, 95% CI: 0.55-0.80, P <0.0001, I2 =80%), and an overall survival benefit for <36 months (HR: 0.87, 95% CI: 0.78-0.98, P =0.02, I2 =0%) but not for >36 months (HR: 0.98, 95% CI: 0.89-1.09, P =0.77, I2 =30%). There was no difference in deaths between intervention and control groups <36 months (RR: 0.95, 95% CI: 0.86-1.04, P =0.26, I2 =10%) or >36 months (RR: 1.02, 95% CI: 0.97-1.06, P =0.50, I2 =0%). Bevacizumab reduced disease progression <36 months (RR: 0.82, 95% CI: 0.72-0.92, P =0.0008, I2 =82%) but not at >36 months (RR: 0.83, 95% CI: 0.58-1.19, P =0.30, I2 =94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. CONCLUSION: Bevacizumab may improve progression-free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months.

Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The relative success of cisplatin-based chemotherapy regimens for PDAC in clinical trials warrants a review of the literature to assess the cumulative results. This study aims to assess the efficacy of cisplatin-containing regimens for PDAC in terms of survival and response outcomes using a systematic review and proportional meta-analysis. METHODS: In this study, an electronic search was conducted on PubMed, Cochrane Library, Scopus, and Google Scholar to find relevant literature. The random effects model was used to assess pooled overall response rate, stable disease rate, progressive disease rate, 1-year overall survival rate, and their 95% CIs. Publication bias was assessed using funnel plot symmetry and the one-tailed Eggers' test. In all cases, p-value < 0.05 was indicative of significant results. The review is registered with PROSPERO: CRD42023459243. RESULTS: A total of 34 studies consisting of 1599 patients were included in this review. All the included studies were of good quality. In total, 906 patients were male, and the median age of the patients was 58-69 years. Overall, 599 patients had cancer of the pancreatic head, 139 had cancer of the pancreatic body, and 102 patients had cancer of the pancreatic tail. The pooled risk ratios (RRs) revealed an overall response rate of 19.2% (95% CI, 14.6-24.2%), a stable disease rate of 42.3% (95% CI, 36.6-48.8), a 1-year overall survival rate of 40% (95% CI, 34.3-45.8), and progressive disease rate of 24.7% (95% CI, 18.8-31.2). Commonly reported adverse events were anemia, thrombocytopenia, abdominal adverse events, neutropenia, fatigue, leukopenia, alopecia, anorexia, mucositis, stomatitis, and hepatobiliary adverse events. CONCLUSION: Cisplatin-containing regimens have shown moderate efficacy with significant improvement in overall survival at 1 year, stable disease rate, and progressive disease rate; however, only a small percentage of patients achieved an overall response rate.