Global Outcomes Research Articles

Parsimonious immune-response endotypes and global outcome in patients with traumatic brain injury

The inflammatory response in patients with traumatic brain injury (TBI) offers opportunities for stratification and intervention. Previous unselected approaches to immunomodulation in patients with TBI have not improved patient outcomes. Serum and plasma samples from two prospective, multi-centre observational studies of patients with TBI were used to discover (Collaborative European NeuroTrauma Effectiveness Research [CENTER-TBI], Europe) and validate (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI] Pilot, USA) individual variations in the immune response using a multiplex panel of 30 inflammatory mediators. Mediators that were associated with unfavourable outcomes (Glasgow outcome score-extended [GOS-E]≤4) were used for hierarchical clustering to identify patients with similar signatures. Two clusters were identified in both the discovery and validation cohorts, termed early-inflammatory and pauci-inflammatory. The early-inflammatory phenotype had higher concentrations of interleukin-6 (IL-6), IL-15, and monocyte chemoattractant protein 1 (MCP1). Patients with the early-inflammatory phenotype were older and more likely to have an unfavourable GOS-E at 6 months. There were no differences in the baseline injury severity scores between patients in each phenotype. A combined IL-15 and MCP1 signature identified patients with the early-inflammatory phenotype in both cohorts. Inflammatory processes mediated outcomes in older patients with moderate-severe TBI. Our findings offer a precision medicine approach for future clinical trials of immunomodulation in patients with TBI, by using inflammatory signatures to stratify patients. CENTER-TBI study was supported by the European Union 7th Framework Programme. TRACK-TBI is supported by the National Institute of Neurological Disorders and Stroke.

Comparative Analysis of Hepatitis C virus Genotype 1a (Isolate 1) using Multiple Regression Algorithms and Fingerprinting Techniques

Approximately 70 million people worldwide have been infected with Hepatitis C virus (HCV), presenting a critical global health challenge. As a member of the Flaviviridae family, HCV can cause severe liver diseases such as cirrhosis, acute hepatitis, and chronic hepatitis. The Hepatitis C virus (HCV) genome encodes a single polyprotein consisting of 3010 amino acids, which when processed contains 10 polypeptides derived from cellular and viral proteases. These include structural proteins such as core protein, E1 and E2 envelope glycoproteins, and nonstructural proteins such as NS1, NS2, NS3, NS4A, NS4B, NS5A, and NS5B. Nonstructural proteins will be released by HCV NS2-3 and NS3-4A proteases, however, structural proteins will be released by host ER signaling peptidases. co-translationally and post-translationally form 10 individual structural proteins: 5'-C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B-3'. Despite extensive research, there are significant gaps in predictive and analytical approaches to managing HCV, particularly in understanding the polyprotein structure and its implications for drug discovery. This study addresses these gaps by employing machine learning techniques to analyze HCV polyprotein using various fingerprinting methods and regression algorithms. The data was sourced from the ChEMBL database, and fingerprinting techniques such as PubChem, MACCS, and E-State were utilized. Regression algorithms, including Gradient Boosting Regression (GBR), Random Forest Regression (RFR), AdaBoost Regression (ABR), and Hist Gradient Boosting Regression (HSR), were applied. Model performance was evaluated using R² and Adjusted R² metrics, comparing default models with those enhanced by hyperparameter tuning. Feature importance analysis was conducted to identify key features influencing model performance, aiding in model simplification. The results show that although hyperparameter tuning does not significantly improve the predictive power of a model, it can provide an insight into model optimization. In particular, the default model showed higher R² and Adjusted R² values across different fingerprinting techniques compared to models with hyperparameterized features. Gradient Boosting Regression (GBR) and Random Forest Regression (RFR) consistently performed well, with GBR showing the highest R² values when using PubChem fingerprints. Although there was no significant improvement through hyperparameter tuning, this study was able to find out the features that strongly influenced the model performance by conducting a feature importance analysis. This analysis helped simplify the model and highlighted the potential of machine learning in improving the understanding of HCV polyprotein structure. This research identifies optimal regression models and fingerprinting techniques, providing a strong framework for future drug discovery efforts aimed at improving global health outcomes. The research also shows that it is important to date to advance drug discovery using machine learning.

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial

Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30mL/min/1.73m2) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19). Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n=45) and 39.8% (n=35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p=0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3mL/min/1.73m2, 90% CI 0.51-8.12, p=0.06; and MAKE 6.7% (n=6) vs 15.9% (n=14); RR: 0.41, 90% CI: 0.19, 0.88, p=0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group). In this proof-of-concept study, RMC-035 did not reduce AKI 72h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes. Guard Therapeutics.

Updated guidelines for chronic kidney disease.

Chronic kidney disease (CKD) is an increasingly common condition worldwide that leads to substantial mortality. Research in the past decade has informed significant advances in preventing CKD or delaying its progression, mainly through new medications. This progress, however, requires adequate screening and identification of early CKD to truly transform patient outcomes. Revised guidelines from the Kidney Disease: Improving Global Outcomes consortium of experts aim to help clinicians incorporate these advances into practice. This article summarizes key updates from the guidelines regarding the evaluation and management of CKD that can lead to better patient outcomes.

A study of the predictive role of multiple variables for the incidence of acute kidney injury and its outcomes in Indian patients with ST-elevation myocardial infarction and cardiogenic shock

BackgroundAcute kidney injury (AKI) occurs frequently in ST-elevation myocardial infarction with cardiogenic shock (CS-STEMI) and is a strong independent prognostic marker for short and intermediate-term outcomes. Owing to the delayed presentation and limited facilities for primary percutaneous coronary intervention in low- and middle-income countries, the incidence, predictors, and outcome of AKI are likely to be different compared to the developed countries. We performed a post hoc analysis of patients presenting with CS-STEMI over 7 years (2016–2022) at a tertiary referral center in North India. The primary outcome assessed was AKI and the secondary outcome was in-hospital mortality.ResultsOf the 426 patients, 194 (45.5%) patients developed AKI, as defined by the Kidney Disease Improving Global Outcomes criteria. Left ventricular (LV) pump failure with pulmonary edema [Odds ratio (OR) 1.67; 95% confidence interval (CI) 1.04–2.67], LV ejection fraction (OR 1.35 per 10% decrease in ejection fraction; CI 1.04–1.73), complete heart block (OR 2.06; CI 1.2–3.53), right ventricular infarction (OR 2.76; CI 1.39–5.49), mechanical complications (OR 3.89; CI 1.85–8.21), ventricular tachycardia (OR 2.80; CI 1.57–4.99), and non-revascularization (OR 2.2; CI 1.33–3.67) were independent predictors of AKI in multivariate logistic regression analysis. Additionally, AKI was a strong predictor of in-hospital mortality (univariate OR 30.61, CI 17.37–53.95).ConclusionsThere is a higher incidence of AKI in CS-STEMI in resource-limited settings and is associated with adverse short-term outcomes. Additional studies are needed to address the optimal strategies for the prevention and management of AKI in such settings.

Proteinuria Assessment and Therapeutic Implementation in Chronic Kidney Disease Patients-A Clinical Audit on KDIGO ("Kidney Disease: Improving Global Outcomes") Guidelines.

Background/Objectives: Chronic kidney disease (CKD) is a major health problem with a rising prevalence due to comorbidities like diabetes and hypertension. The aim of this research was to audit the assessment and therapeutic management of proteinuria in CKD patients at the Cantonal Hospital Baselland (KSBL) in Switzerland and determine associations between patient comorbidities, rehospitalisation, death, and the quality of therapeutic management. Methods: We analysed data from 427 adults with CKD (eGFR < 45 mL/min/1.73 m2) hospitalised on the internal medicine ward in 2022. Results: The mean age was 85 years (range: 79-89), 45.9% were female, and the median eGFR was 32.8 mL/min/1.73 m2 (range: 25-40). Proteinuria assessment was performed in 120 (28.1%) patients (the ProtU group), and a corresponding treatment was prescribed in 59%. The ProtU group had a higher quota of patients with diabetes (44.1% vs. 33%, p = 0.048) and obesity (21.2% vs. 12.5%, p = 0.039) when compared to the group without proteinuria assessment (the Ustix group). Twelve-month survival was not significantly different between the groups (HR: 0.75; 95% CI: 0.488-1.154; p-value = 0.191). However, survival was significantly better in patients who received an antiproteinuric treatment compared to those who did not (HR: 0.30; 95% CI: 0.121-0.0761; p = 0.011). Conclusions: Improvements need to be made in managing CKD at the KSBL in accordance with the guidelines.

The association of acute and chronic phase cerebrovascular reactivity with patient reported quality of life following moderate-to-severe traumatic brain injury

Global outcomes have been reported to be associated with cerebrovascular reactivity (CVR) in the acute phase following moderate and severe traumatic brain injury (TBI). The association of CVR in the acute and chronic phase of injury with patient-reported health-related quality of life metrics (HRQOL) metrics has never been explored. The aim of this study is to examine the association of CVR, as measured by the cerebral oxygen indices (COx and COx_a), in the acute and chronic phase following moderate and severe TBI, with patient reported HRQOL. In this prospective cohort study, performed in a Canadian quaternary care center, the association between continuous acute and chronic phase CVR with patient reported HRQOL outcomes following moderate and severe TBI was examined. The main outcomes of interest of this study were validated measures of patient-reported HRQOL over various domains as measured by both the 12-Item Short-Form Health Survey (SF-12) and a Quality of Life after Brain Injury (QOLIBRI) questionnaire. In the 29 subjects of this cohort, acute phase CVR was found to be significantly more active in those with a favorable Mental Component Summary (MCS) scores of the SF-12 at early follow-up when measured by COx (-0.015 [IQR: -0.067 to 0.032] vs 0.040 [IQR: 0.019 to 0.137] for Favorable first MCS vs Unfavorable respectively; Mann–Whitney U test p-value = 0.046) and COx_a (0.038 [IQR: 0.009 to 0.062] vs 0.112 [IQR: 0.065 to 0.167] for Favorable first MCS vs Unfavorable respectively; Mann–Whitney U test p-value = 0.014). Further, multivariable logistic regression analysis found acute phase COx and COx_a to improve model performance when predicting favorable versus unfavorable early MCS scores over established parameters such as age and measures of injury severity. Associations between outcomes and chronic phase CVR were limited, potentially due to short recording periods. This is the first ever pilot study to identify a relationship between acute phase CVR following moderate-to-severe TBI with mental and cognitive outcomes as experienced by patients. Given the small cohort, these findings will need to be confirmed in a larger multicenter study. This highlights the need for additional examination of the role dysfunctional CVR may play in mental and cognitive outcomes, as well as patient-reported outcomes more generally following TBI.

Inflammatory response to sars-CoV 2 and other respiratory viruses.

Lower respiratory tract infections (LRTI) remain a significant global cause of mortality and disability. Viruses constitute a substantial proportion of LRTI cases, with their pandemic potential posing a latent threat. After the SARS-CoV-2 pandemic, the resurgence of other respiratory viruses, including Influenza and Respiratory Syncytial Virus responsible for LRTI has been observed especially in susceptible populations. This review details the inflammatory mechanisms associated with three primary respiratory viruses: SARS-CoV-2, Influenza, and Respiratory Syncytial Virus (RSV). The focus will be on elucidating the activation of inflammatory pathways, understanding cellular contributions to inflammation, exploring the role of interferon and induced cell death in the response to these pathogens and detailing viral evasion mechanisms. Furthermore, the distinctive characteristics of each virus will be explained. The study of viral pneumonia, notably concerning SARS-CoV-2, Influenza, and RSV, offers critical insights into infectious and inflammatory mechanisms with wide-ranging implications. Addressing current limitations, such as diagnostic accuracy and understanding host-virus interactions, requires collaborative efforts and investment in technology. Future research holds promise for uncovering novel therapeutic targets, exploring host microbiome roles, and addressing long-term sequelae. Integrating advances in molecular biology and technology will shape the evolving landscape of viral pneumonia research, potentially enhancing global public health outcomes.

Analyzing and Critically Evaluating the Problems of Antiviral Chemotherapy

Antiviral chemotherapy, an indispensable tool in combating viral infections, faces numerous challenges that often undermine its overall effectiveness and application. This review critically examines the multifaceted issues associated with antiviral chemotherapy, drawing on comprehensive data from NCBI, PubMed, and other reputable academic sources. The primary purpose of this research is to analyze and evaluate key problems such as the development of drug resistance, narrow therapeutic windows, limited spectrum of activity, toxicity, high costs, viral latency, and the complexities inherent in combination therapy. These challenges necessitate a delicate and strategic balance in the development, regulation, and application of antiviral drugs. The research methodology included an exhaustive review of peer-reviewed articles and clinical studies sourced from PubMed and NCBI databases, focusing on ten critical challenges in antiviral chemotherapy. The findings underscore the persistent issue of drug resistance, particularly in RNA viruses like HIV and hepatitis C, which demand ongoing innovation in antiviral drug design and implementation. Additionally, the analysis reveals the significant risks posed by the narrow therapeutic index of many antiviral drugs, which often increases the likelihood of adverse effects, thus limiting their safe and effective use. The study also highlights the formidable challenges posed by viral latency and the limited efficacy of current therapies against emerging and re-emerging viral threats. This research significantly contributes to the understanding of the inherent limitations in existing antiviral therapies and underscores the pressing need for more effective, accessible, and safe treatments. The practical significance lies in offering insights that could guide future research, clinical practice, and policy decisions, ultimately improving global health outcomes in the fight against viral diseases.

Effects of ertugliflozin on uric acid and gout-related outcomes in persons with type 2 diabetes and cardiovascular disease: Post hoc analyses from VERTIS CV.

To conduct post hoc analyses of the VERTIS CV (NCT01986881) trial to explore the effects of ertugliflozin on serum uric acid (UA) and gout-related outcomes. Participants with type 2 diabetes and atherosclerotic cardiovascular disease were randomised (1:1:1) to placebo, ertugliflozin 5 mg or ertugliflozin 15 mg. Mean UA over time (260 weeks) was evaluated for pooled ertugliflozin versus placebo overall, and by baseline quintile of UA (≤4.3 mg/dL [≤255.8 µmol/L], >4.3-5.1 mg/dL [>255.8-303.4 µmol/L], >5.1-5.8 mg/dL [>303.4-345.0 µmol/L], >5.8-6.9 mg/dL [>345.0-410.4 µmol/L] and >6.9 mg/dL [>410.4 µmol/L]), glycated haemoglobin level, albuminuria status, estimated glomerular filtration rate and KDIGO (Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease) risk category. The effect of ertugliflozin on a composite of gout onset or initiation of anti-gout medication was assessed. The mean UA levels at baseline were 5.67 and 5.62 mg/dL in the placebo and ertugliflozin groups, respectively. Ertugliflozin reduced UA over Weeks 6-260 compared with placebo, with least squares mean (LSM) changes (95% confidence interval [CI]) from baseline at Week 260 of 0.07 mg/dL (-0.02, 0.15) and -0.19 mg/dL (-0.25, -0.13) in the placebo and pooled ertugliflozin groups, respectively. At Week 260, placebo-adjusted LSM change (95% CI) from baseline in UA was -0.26 mg/dL (-0.36, -0.16) with ertugliflozin. Ertugliflozin was associated with reductions in UA across baseline UA quintiles compared with placebo. The incidence of the composite of gout-related outcomes was 84/2539 (3.3%) for placebo and 133/5091 (2.6%) for ertugliflozin (hazard ratio for the composite 0.76 [95% CI 0.580, 1.002]). Ertugliflozin was generally associated with lowering UA overall and across subgroups compared with placebo, and numerically reduced rates of gout-related outcome events.

680. P02.06 MATTERHORN PCR BY REGION

Abstract Background FLOT was established as a perioperative therapy for GC/GEJC following the Phase 2/3 FLOT4 study conducted in Germany, with a pCR rate of 16% (Al-Batran et al, Lancet Oncol 2016). The global MATTERHORN study (NCT04592913) showed a statistically significant improvement in pCR with perioperative D+FLOT vs placebo (P) + FLOT in GC/GEJC at first interim analysis (Janjigian et al, ESMO Congress 2023). Subgroup analyses by region and country were completed to assess pCR rates with FLOT and benefit of D+FLOT across the global study population. Methods Participants (pts) with resectable GC/GEJC were randomized 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT Q2W on Days 1 and 15 for 4 cycles (2 doses of D or P and 4 doses of FLOT pre- and post-operative), followed by D 1500 mg or P on Day 1 Q4W for 10 further cycles. Randomization was stratified by Asia vs non-Asia. pCR (Modified Ryan; central review) was assessed in prespecified (Asia) and post hoc regional subgroups, including 6 countries with the highest numbers of randomized pts. Results Of 948 pts randomized globally, 180 (19%) were in Asia. pCR outcomes with FLOT in Asia were consistent with global outcomes. pCR rates were improved with D+FLOT vs P+FLOT in all regions (Asia, Europe, North America and South America; Table), despite some imbalances in baseline characteristics and numerical differences in pCR rates by geographic location. The pCR rate with P+FLOT in the German subgroup (13%; 95% CI, 6.1–23.0) was similar to that with FLOT in the FLOT4 study. Improvement in pCR with D+FLOT vs P+FLOT was observed across subgroups by country. Similar trends across regional subgroups were observed for combined complete and near-complete response rate. Conclusions In MATTERHORN, pCR was consistently improved with the addition of D to perioperative FLOT in GC/GEJC across geographic regions. The study is ongoing for the primary objective of event-free survival.

Treatment and rehabilitation of subtalar dislocations: A case series and a review of the literature.

Subtalar dislocation is an uncommon orthopaedic pathology, representing 1 % of all traumatic injuries of the foot and 1-2 % of all dislocations, mostly affecting young male adults. While its urgent treatment consisting in reduction and immobilization of the dislocation has been well described, disagreement exists about post-operative management with specific regards to immobilization length and rehabilitation protocols. A case series of traumatic subtalar dislocations treated with urgent reduction, a mean of 4 weeks immobilization and subsequent rehabilitation is presented, with 1-year minimum clinical and subjective follow up. Also, a systematic review of the literature concerning the post-operative management following a subtalar dislocation, and subsequent results, has been performed. At 1-year minimum follow up, none of the patients presented with complications such as recurrence of dislocation or talus osteonecrosis. Tibio-talar and subtalar range of motion (ROM) were superimposable to the contralateral joints, with a maximum difference of 5°. The American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Score highlighted a good functionality and a full recovery in all patients but one. Pure subtalar dislocations led to better results than complicated ones. Review of current literature available on the topic demonstrated that an earlier mobilization resulted in better ROM, but the global outcome did not differ among 4 to 6 weeks of immobilization. Conflicting reports are present in the literature regarding the most appropriate post-reduction management of subtalar dislocations. In our case series, successful results have been obtained with a mean of 4 weeks of limb immobilization and an early rehabilitation protocol. Although some limitations are present, 4 weeks immobilization appears to be the best balance between a good overall outcome and a better recovery of ROM. Further studies are needed to deepen the subject.

Real World Outcome of High-Risk Multiple Myeloma: An Indian Tertiary Care Centre Experience

IntroductionHigh risk myeloma is heterogeneous with significant variation in risk stratifications. Real world outcomes differ from controlled clinical trials and affected by socioeconomical determinants. Material and methodsThis retrospective study was performed in a North Indian teriarty care cancer hospital. Out of 384,76(19.7%) high risk myeloma patients (median age 58 years) were analyzed. Result and conclusionMost common HRCA was 1 q gain 36(47.4%) followed by del17p 32(42.1%). 61/76(80.2%) received bortezomib based triplets and 15(19.74%) daratumumab based quadruplets induction, 31(40.79%) received ASCT. Median duration of follow up was 19.5 months. The 2 year OS and PFS was 73.8%, 52.6% respectively. Estimated 3 year OS was 74.7% in ASCT cohort versus 52.9% (P = .0067) without. Estimated 3-year PFS in the ASCT cohort was 72.1% versus 30.3% (P = .0026) without. Estimated 3-year OS for single hit and multi hit ultra HRMM was 67.7% and 61.9% (P = .642) whereas PFS was 58.2% and 35.2% (P = .486) respectively. In multivariate analysis ASCT correlated with better OS (HR 0.3, P = .041) and PFS (HR 0.35, P = .012). Absence of baseline renal impairment correlated with better OS (HR 4.12, P = .004) only. Early aggressive therapy with prompt ASCT translates to a better survival in high risk myeloma. Emphasis on real world clinical outcome is the need of the hour for addressing practical issues and improving global myeloma outcome.

Neurological Manifestation of Neonatal Acute Kidney Injury: Focusing on the Clinico-Radiological Profile.

Purpose This study aimed atstudying the neurological manifestation of neonatal acute kidney injury, focusing on the clinico-radiological profile. Methodology In this cross-sectional study, newborns hospitalized in the neonatal intensive care unit of a tertiary care hospital were enrolled over a study period of one year. As per the Kidney Disease: Improving Global Outcome (KDIGO) criteria, 74 neonates were enrolled, and magnetic resonance imaging (MRI) was performed on the same neonates. Result In this study, acute kidney injury (AKI) was seen more often in neonates with admission weights between 1,500 and 2,499 grams, accounting for 52.7% of total study participants. In the current study, neonates admitted with AKI presented more with signs and symptoms of encephalopathy, such as lethargy (78.4%), seizures (64.8%), and irritability (35.1%) at admission. Signs and symptoms of fever and decreased urine output were more common after the first week of life. Abnormal MRI findings were observed in 64.9% of neonates with AKI. The mean blood urea and serum creatinine levels in neonates with abnormal MRI were 188.14 ± 108.25 mg/dL and 2.93 ± 2.16 mg/dL, respectively. The mean blood urea and serum creatinine levels in neonates with normal MRI were 169.84 ± 65.45 mg/dL and 2.41 ± 1.85 mg/dL, respectively. Of the 74 neonates enrolled with AKI, 12 (16.21%) had CSVT. These neonates had a mean blood urea level of 231.58 ± 111.66 mg/dL (p = 0.047) and a mean creatinine level of 3.77 ± 2.78 mg/dL. Conclusion Neonatal AKI has a variable presentation with high mortality and morbidity. Elevated serum urea and creatinine can be used to predict CSVT.

Association of Preoperative Neutrophil to Lymphocyte Ratio with Early Postoperative Acute Kidney Injury Following Isolated Off-Pump Coronary Artery Bypass Grafting

Objective: Acute kidney injury (AKI) is a frequent complication after off-pump coronary artery bypass grafting (OPCAB) that complicates recovery, increases treatment cost and mortality. Neutrophil to lymphocyte ratio (NLR) is a systemic inflammatory marker easily derived from complete blood count that has many prognostic potentials. The purpose of this study was to evaluate if there is an association of preoperative NLR with early postoperative AKI following isolated OPCAB. Methods: This cross-sectional study was carried out in the Department of Cardiac Surgery, National Institute of Cardiovascular Diseases (NICVD) on a total of 60 patients aged 31-70 years with no preoperative renal dysfunction undergoing isolated OPCAB between August 2021 and July 2022. Group A included 30 patients with preoperative NLR &lt; 2.65 and Group B included 30 patients with preoperative NLR ≥ ≥≥2.65. Patients were monitored for development of early postoperative AKI according to serum creatinine criteria of Kidney Disease Improving Global Outcomes (KDIGO) 2012 guideline. Results: Two patients from group A and twenty patients from group B developed early postoperative AKI (p &lt; 0.001). Events of AKI were significantly higher in group B patients at all postoperative time points. Multivariate binary logistic regression analysis revealed preoperative NLR ≥ ≥≥2.65 as an independent predictor of early post OPCAB AKI (p = 0.004, OR = 13.746). In receiver operating curve (ROC) analysis area under curve (AUC) was 0.933 (95% CI 0.874-0.992, p &lt; 0.001). It showed 90.91% sensitivity and 73.7% specificity at the pre-set cut off value of NLR at 2.65 where optimal predictability of post-OPCAB AKI occurred with 66.67% positive predictive value, 93.33% negative predictive value and 80% accuracy. Conclusion: Preoperative NLR is significantly associated with early postoperative AKI following isolated OPCAB and therefore it should be incorporated in routine clinical practice for early prediction of AKI and implementing timely preventive strategies. (Bangladesh Heart Journal 2024; 39(2): 151-160

Sodium-glucose co-transporter-2 inhibitors in patients with chronic kidney disease with or without type 2 diabetes: systematic review and meta-analysis

ObjectiveTo examine cardiovascular and kidney benefits and harms of sodium-glucose co-transporter-2 (SGLT-2) inhibitors stratified by risk in adults with chronic kidney disease regardless of diabetes status.DesignSystematic review and meta-analysis.Data sourcesOvid...

Acute kidney injury: the experience of a tertiary center of Pediatric Nephrology.

Acute kidney injury (AKI) is an abrupt deterioration of kidney function. The incidence of pediatric AKI is increasing worldwide, both in critically and non-critically ill settings. We aimed to characterize the presentation, etiology, evolution, and outcome of AKI in pediatric patients admitted to a tertiary care center. We performed a retrospective observational single-center study of patients aged 29 days to 17 years and 365 days admitted to our Pediatric Nephrology Unit from January 2012 to December 2021, with the diagnosis of AKI. AKI severity was categorized according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The outcomes considered were death or sequelae (proteinuria, hypertension, or changes in renal function at 3 to 6 months follow-up assessments). Forty-six patients with a median age of 13.0 (3.5-15.5) years were included. About half of the patients (n = 24, 52.2%) had an identifiable risk factor for the development of AKI. Thirteen patients (28.3%) were anuric, and all of those were categorized as AKI KDIGO stage 3 (p < 0.001). Almost one quarter (n = 10, 21.7%) of patients required renal replacement therapy. Approximately 60% of patients (n = 26) had at least one sequelae, with proteinuria being the most common (n = 15, 38.5%; median (P25-75) urinary protein-to-creatinine ratio 0.30 (0.27-0.44) mg/mg), followed by reduced glomerular filtration rate (GFR) (n = 11, 27.5%; median (P25-75) GFR 75 (62-83) mL/min/1.73 m2). Pediatric AKI is associated with substantial morbidity, with potential for proteinuria development and renal function impairment and a relevant impact on long-term prognosis.

Analysis of the PARAGON-HF Study Results Using Win Ratio.

The PARAGON-HF study (Prospective Comparison of ARNI With ARB Global Outcomes in Heart Failure With Preserved Ejection Fraction) investigated the effect of sacubitril-valsartan in heart failure (HF) with preserved ejection fraction. The results, which were analyzed using conventional statistical methods, did not find a significant reduction in the primary composite end point of cardiovascular death and total hospitalization for HF. Recent clinical trials used win ratio statistics that enable the incorporation of multiple outcome aspects into the primary end point and can detect positive outcomes with fewer patients. In this study, we assessed the effect of sacubitril-valsartan on outcomes using the win ratio to analyze results from patients included in the PARAGON-HF study. In the PARAGON-HF study, 4822 patients with HF with preserved ejection fraction were randomized either to sacubitril-valsartan or valsartan groups. In the present study, the primary outcome was a hierarchical composite of time to cardiovascular death, total number of hospitalization for HF, time to first hospitalization for HF, time to renal composite outcome, and change in the Kansas City Cardiomyopathy Questionnaire total symptom score at 8 months analyzed using a win ratio statistical model. Using this approach, we found that a greater number of patients who received sacubitril-valsartan experienced clinical benefits compared with those who received valsartan (win ratio, 1.13 [95% CI, 1.04-1.23]; P=0.005). This clinical advantage was evident in patients regardless of whether the left ventricular ejection fraction was above or below the median, that is, the left ventricular ejection fraction of 57%, and regardless of sex (Pinteraction=0.76 for the left ventricular ejection fraction and 0.73 for sex). Employing the innovative win ratio approach, sacubitril-valsartan demonstrated significant clinical benefits among patients with HF with preserved ejection fraction. Notably, this benefit was observed irrespective of left ventricular ejection fraction and sex. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Risk factors analysis for severe acute kidney injury in septic patients and establishment and validation of an hour-specific prediction model

To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model. Based on the information of septic patients in the Medical Information Mart for Intensive Care- IV (MIMIC- IV) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7 : 3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model. A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio (HR) = 1.266, 95% confidence interval (95%CI) was 1.150-1.393], heart failure (HR = 1.348, 95%CI was 1.217-1.493), respiratory failure (HR = 1.565, 95%CI was 1.428-1.715), heart rate (HR = 1.004, 95%CI was 1.002-1.007), mean arterial pressure (HR = 1.245, 95%CI was 1.126-1.377), lactic acid (HR = 1.051, 95%CI was 1.025-1.077), simplified acute physiology score II (SAPS II, HR = 1.019, 95%CI was 1.016-1.023), serum creatinine (HR = 1.171, 95%CI was 1.127-1.216), anion gap (HR = 1.024, 95%CI was 1.010-1.038), serum potassium (HR = 1.155, 95%CI was 1.079-1.236), white blood cell count (HR = 1.006, 95%CI was 1.003-1.009) and furosemide use (HR = 0.414, 95%CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95%CI was 0.782-0.808), 0.792 (95%CI was 0.780-0.805), and 0.775 (95%CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95%CI was 0.784-0.823), 0.791 (95%CI was 0.772-0.810), and 0.773 (95%CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.

Pilot Trial of Hydroxychloroquine as Add-On Therapy in Patients With Membranous Nephropathy

BackgroundKidney Disease Improving Global Outcomes guidelines indicate that glucocorticoids and immunosuppressants comprise the first therapeutic regimens after 4–6 months of treatment for high-risk primary membranous nephropathy (PMN). However, some patients cannot achieve complete or partial remission at 6 months. This study aimed to evaluate the efficacy of traditional immunotherapy combined with hydroxychloroquine (HCQ), a well-known immune regulator, in patients with PMN. MethodsThis was a single-center, open-label, prospective study. We recruited 72 patients with nephrotic syndrome and PMN proven by renal biopsy from May 2020 to June 2024. We compared changes in proteinuria, serum albumin levels, estimated glomerular filtration rate, and relapse rate at 3, 6, 9, and 12 months follow up in 41 patients who received glucocorticoid and immunosuppressant, and in 31 who received HCQ plus standard-of-care. ResultsBaseline characteristics showed no statistical significance between the two groups. However, the HCQ group showed significantly reduced proteinuria compared to standard-of-care group. A reduced proteinuria was seen at 6 months [1.2 (0.4, 2.2) vs. 2.2 (1.0, 3.8) g/day, P = 0.029] and the relapse rate with 12 months follow up was also significantly decreased in HCQ group compared to standard-of-care group (3.7% vs. 23.3%, P = 0.033). ConclusionsHCQ may serve as an effective add-on therapy for primary membranous nephropathy.