Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU.

Aim and background: Neutrophil CD64 (nCD64) is evolving as a prognostic biomarker in sepsis. The primary objective of this study was to evaluate whether serial trend of nCD64, procalcitonin (PCT), and C-reactive protein (CRP) predict 28-day mortality in patients with sepsis/septic shock, as per Sepsis-3 criteria. Materials and methods: This prospective, observational single-center cohort study included 60 adult patients (age ≥18 years) with sepsis. Serial biomarker levels with SOFA score were measured at admission (day 0), on day 4, and on day 8. Results: Of the 60 patients, 42 (70%) had septic shock. Biomarker levels at admission did not differ between patients with sepsis and septic shock. Thirty-seven patients survived and 23 were non-survivors by day 28. There was a significant fall in serial trend of all three biomarkers from admission till day 8 (Friedman p < 0.001) in survivors compared to a non-significant change in non-survivors. On multivariate analysis, SOFA score at admission (OR 1.731), more days with vasopressor support (OR 1.077), rise in CD64 from day 0 to day 8 (OR 1.074), and rise in CRP from day 0 to 8 (OR 1.245) were the significant predictors of 28-day mortality (p < 0.05). The highest area under the ROC curve was obtained for more days of vasopressor therapy (0.857), followed by a rise in CD64 from day 0 to day 8 (0.798). Conclusion: Serial trend of biomarkers has prognostic utility. The rise in CD64 from day 0 to day 8 was a good predictor of mortality compared to the trend of other biomarkers. How to cite this article: Patnaik R, Azim A, Singh K, Agarwal V, Mishra P, Poddar B, et al. Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU. Indian J Crit Care Med 2024;28(8):777-784.

Analgesic effect and efficacy rate of radial extracorporeal shock wave therapy for plantar fasciitis: a retrospective study.

[Purpose] This study aimed to measure the analgesic effects and efficacy of radial extracorporeal shock wave therapy, for which no consensus has been reached regarding optimal treatment parameters. [Participants and Methods] The study included 40 feet of 40 patients with plantar fasciitis. The visual analogue scale was used to determine the immediate and cumulative effects of radial extracorporeal shock wave therapy as well as the efficacy rate. Efficacy was calculated as a percentage visual analogue scale change of ≥20 mm and visual analogue scale improvement of ≥60%. [Results] Immediate and continued efficacy of radial extracorporeal shock wave therapy was observed and recorded. Efficacy rates based on a percentage visual analogue scale change of ≥20 mm and visual analogue scale improvement of ≥60% were both 57.5%. [Conclusion] Radial extracorporeal shock wave therapy has immediate and cumulative analgesic effects on plantar fasciitis. However, cumulative results of interventions with various treatment parameters are required to determine the optimal treatment parameter settings for diffuse pressure wave therapy for plantar fasciitis.

Comparison of Modified Early Warning Score (MEWS), Simplified Acute Physiology Score II (SAPS II), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) for early prediction of septic shock in diabetic patients in Emergency Departments.

INTRODUCTION: Sepsis is a severe medical condition that can be life-threatening. If sepsis progresses to septic shock, the mortality rate increases to around 40%, much higher than the 10% mortality observed in sepsis. Diabetes increases infection and sepsis risk, making management complex. Various scores of screening tools, such as Modified Early Warning Score (MEWS), Simplified Acute Physiology Score (SAPS II), Sequential Organ Failure Assessment Score (SOFA), and Acute Physiology and Chronic Health Evaluation (APACHE II), are used to predict the severity or mortality rate of disease. Our study aimed to compare the effectiveness and optimal cutoff points of these scores. We focused on the early prediction of septic shock in patients with diabetes in the Emergency Department (ED). METHODS: We conducted a retrospective cohort study to collect data on patients with diabetes. We collected prediction factors and MEWS, SOFA, SAPS II and APACHE II scores to predict septic shock in these patients. We determined the optimal cutoff points for each score. Subsequently, we compared the identified scores with the gold standard for diagnosing septic shock by applying the Sepsis-3 criteria. RESULTS: Systolic blood pressure (SBP), peripheral oxygen saturation (SpO2), Glasgow Coma Scale (GCS), pH, and lactate concentrations were significant predictors of septic shock (p < 0.001). The SOFA score performed well in predicting septic shock in patients with diabetes. The area under the receiver operating characteristics (ROC) curve for the SOFA score was 0.866 for detection within 48 h and 0.840 for detection after 2 h of admission to the ED, with the optimal cutoff score of ≥ 6. CONCLUSION: SBP, SpO2, GCS, pH, and lactate concentrations are crucial for the early prediction of septic shock in patients with diabetes. The SOFA score is a superior predictor for the onset of septic shock in patients with diabetes compared with MEWS, SAPS II, and APACHE II scores. Specifically, a cutoff of ≥ 6 in the SOFA score demonstrates high accuracy in predicting shock within 48 h post-ED visit and as early as 2 h after ED admission.

Prognostic risk factors for pyogenic liver abscess caused by Klebsiella pneumoniae.

BACKGROUND: Pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae can vary in severity, and several risk factors for the development of organ dysfunction in PLA have been implicated. However, few studies to date have explored the most common risk factors for clinical severity. METHODS: We conducted a study on patients with PLA caused by Klebsiella pneumoniae between February 2013 and December 2022.Using logistic regression analysis, we sought to identify factors associated with positive blood culture, septic shock, and intensive care unit (ICU) admission. RESULTS: After included 200 patients, we found that an elevated procalcitonin (PCT) level (p = 0.03), higher glucose level (p = 0.03), and lower total cholesterol (TC) level (p = 0.01) were associated with a higher likelihood of positive blood bacteriological culture. Additionally, an increased PCT level (p = 0.02) and lower TC level (p < 0.01) were associated with an elevated risk of septic shock. Furthermore, a higher PCT level (p < 0.01) was associated with a higher probability of ICU admission. CONCLUSION: In patients with PLA caused by Klebsiella pneumoniae, the PCT, glucose, and TC levels were found to be associated with positive blood culture, septic shock, and ICU admission.

Occupational risks associated with chronic kidney disease of non-traditional origin (CKDnt) in Brazil: it is time to dig deeper into a neglected problem / Riscos ocupacionais associados à doença renal crônica de origem não tradicional (DRCnt) no Brasil: é hora de nos aprofundarmos em um problema negligenciado

Abstract In the past decades, an epidemic of chronic kidney disease (CKD) has been associated with environmental and occupational factors (heat stress from high workloads in hot temperatures and exposure to chemicals, such as pesticides and metals), which has been termed CKD of non-traditional origin (CKDnt). This descriptive review aims to present recent evidence about heat stress, pesticides, and metals as possible causes of CKDnt and provide an overview of the related Brazilian regulation, enforcement, and health surveillance strategies. Brazilian workers are commonly exposed to extreme heat conditions and other CKDnt risk factors, including increasing exposure to pesticides and metals. Furthermore, there is a lack of adequate regulation (and enforcement), public policies, and strategies to protect the kidney health of workers, considering the main risk factors. CKDnt is likely to be a significant cause of CKD in Brazil, since CKD's etiology is unknown in many patients and several conditions for its development are present in the country. Further epidemiological studies may be conducted to explore causal associations and estimate the impact of heat, pesticides, and metals on CKDnt in Brazil. Moreover, public policies should prioritize reducing workers´ exposure and promoting their health and safety.

Resumo Nas últimas décadas, uma epidemia de doença renal crônica (DRC) tem sido associada a fatores ambientais e ocupacionais (estresse térmico decorrente de cargas de trabalho elevadas em altas temperaturas e exposição a produtos químicos, como agrotóxicos e metais), denominada DRC de origem não tradicional (DRCnt). Esta revisão descritiva tem como objetivo apresentar evidências recentes sobre estresse térmico, agrotóxicos e metais como possíveis causas de DRCnt e fornecer uma visão geral das estratégias brasileiras de regulamentação, fiscalização e vigilância sanitária relacionadas. Os trabalhadores brasileiros são comumente expostos a condições extremas de calor e outros fatores de risco de DRCnt, incluindo o aumento da exposição a agrotóxicos e metais. Além disso, há uma falta de regulamentação e fiscalização, políticas públicas e estratégias adequadas para proteger a saúde renal dos trabalhadores em relação aos principais fatores de risco. É provável que a DRCnt seja uma causa significativa de DRC no Brasil, uma vez que a etiologia da doença é desconhecida em muitos pacientes e diversas condições para seu desenvolvimento estão presentes no país. Estudos epidemiológicos devem ser realizados para explorar associações causais e estimar o impacto do calor, dos agrotóxicos e dos metais na DRCnt no Brasil. Além disso, as políticas públicas devem priorizar a redução da exposição dos trabalhadores e a promoção de sua saúde e segurança.

Phenotyping Refractory Cardiogenic Shock Patients Receiving Venous-Arterial Extracorporeal Membrane Oxygenation Using Machine Learning Algorithms.

Background: This study used machine learning to categorize cardiogenic shock (CS) patients treated with venous-arterial extracorporeal membrane oxygenation (VA-ECMO) into distinct phenotypes. Subsequently, it aimed to clarify the wide mortality variance observed in refractory CS, attributing it to the condition's inherent heterogeneity. Methods: This study enrolled a cohort of CS patients who received VA-ECMO support. By employing rigorous machine learning (ML) techniques, we generated and validated clusters based on determinants identified through algorithmic analysis. These clusters, characterized by distinct clinical outcomes, facilitated the examination of clinical and laboratory profiles to enhance the understanding of patient responses to VA-ECMO treatment. Results: In a study of 210 CS patients undergoing VA-ECMO treatment, 70.5% were male with a median age of 62, ranging from 53 to 67 years. Survival rates were 67.6% during VA-ECMO and 49.5% post-discharge. Patients were classified into three phenotypes based on the clinical and laboratory findings: "platelet preserved (I)", those with stable platelet counts, "hyperinflammatory (II)", those indicating significant inflammation, and "hepatic-renal (III)", those showing compromised liver and kidney functions. Mortality rates (25.0%, 52.8%, and 55.9% for phenotypes I, Ⅱ, and Ⅲ, respectively (p = 0.005)) varied significantly among these groups, highlighting the importance of phenotype identification in patient management. Conclusions: This study identified three distinct phenotypes among refractory CS patients treated using VA-ECMO, each with unique clinical characteristics and mortality risks. Thus, highlighting the importance of early detection and targeted intervention, these findings suggest that proactive management could improve outcomes for those showing critical signs.

The Association between Cardiac Arrest and Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock.

Background: The impact of cardiac arrest (CA) at admission on the prognosis of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains a subject of debate. Methods: We conducted a retrospective study at West China Hospital from 2018 to 2021, enrolling 247 patients with AMI complicated by CS (AMI-CS). Patients were categorized into CA and non-CA groups based on their admission status. Univariate and multivariate Cox regression analyses were performed, with 30-day and 1-year mortality as the primary endpoints. Kaplan-Meier plots were constructed, and concordance (C)-indices of the Global Registry of Acute Coronary Event (GRACE) score, Intra-aortic Balloon Pump in Cardiogenic Shock (IABP-SHOCK) II score, and IABP-SHOCK II score with CA were calculated. Results: Among the enrolled patients, 39 experienced CA and received cardiopulmonary resuscitation at admission. The 30-day and 1-year mortality rates were 40.9% and 47.0%, respectively. Neither univariate nor multivariate Cox regression analyses identified CA as a significant risk factor for 30-day and 1-year mortality. In C-statistics, the GRACE score exhibited a moderate effect (C-indices were 0.69 and 0.67, respectively), while the IABP-SHOCK II score had a better predictive performance (C-indices were 0.79 and 0.76, respectively) for the 30-day and 1-year mortality. Furthermore, CA did not enhance the predictive value of the IABP-SHOCK II score for 30-day (p = 0.864) and 1-year mortality (p = 0.888). Conclusions: Cardiac arrest at admission did not influence the survival of patients with AMI-CS. Active resuscitation should be prioritized for patients with AMI-CS, regardless of the presence of cardiac arrest.

Preoperative renal arterial embolization in high-risk nephrectomy: A case report of a 48-year-old patient with severe emphysematous pyelonephritis.

A 48-year-old female with a background history of alcoholic liver cirrhosis and noninsulin-dependent diabetes presented to our institution with emphysematous pyelonephritis of the right kidney diagnosed on CT. Both urine and blood culture grew multidrug-resistant Escherichia coli. The patient developed severe thrombocytopenia, hyponatremia, confusion as well as septic shock. Preoperative right renal arterial embolization was performed, followed by immediate primary nephrectomy. This article reports the first documented case of preoperative angioembolization to prevent severe intraoperative hemorrhage and vascular complications in severe emphysematous pyelonephritis.

Refinement of machine learning arterial waveform models for predicting blood loss in canines.

Introduction: Hemorrhage remains a leading cause of death in civilian and military trauma. Hemorrhages also extend to military working dogs, who can experience injuries similar to those of the humans they work alongside. Unfortunately, current physiological monitoring is often inadequate for early detection of hemorrhage. Here, we evaluate if features extracted from the arterial waveform can allow for early hemorrhage prediction and improved intervention in canines. Methods: In this effort, we extracted more than 1,900 features from an arterial waveform in canine hemorrhage datasets prior to hemorrhage, during hemorrhage, and during a shock hold period. Different features were used as input to decision tree machine learning (ML) model architectures to track three model predictors-total blood loss volume, estimated percent blood loss, and area under the time versus hemorrhaged blood volume curve. Results: ML models were successfully developed for total and estimated percent blood loss, with the total blood loss having a higher correlation coefficient. The area predictors were unsuccessful at being directly predicted by decision tree ML models but could be calculated indirectly from the ML prediction models for blood loss. Overall, the area under the hemorrhage curve had the highest sensitivity for detecting hemorrhage at approximately 4 min after hemorrhage onset, compared to more than 45 min before detection based on mean arterial pressure. Conclusion: ML methods successfully tracked hemorrhage and provided earlier prediction in canines, potentially improving hemorrhage detection and objectifying triage for veterinary medicine. Further, its use can potentially be extended to human use with proper training datasets.

The Indian Society of Critical Care Medicine Position Statement on the Management of Sepsis in Resource-limited Settings.

Sepsis poses a significant global health challenge in low- and middle-income countries (LMICs). Several aspects of sepsis management recommended in international guidelines are often difficult or impossible to implement in resource-limited settings (RLS) due to issues related to cost, infrastructure, or lack of trained healthcare workers. The Indian Society of Critical Care Medicine (ISCCM) drafted a position statement for the management of sepsis in RLS focusing on India, facilitated by a task force of 18 intensivists using a Delphi process, to achieve consensus on various aspects of sepsis management which are challenging to implement in RLS. The process involved a comprehensive literature review, controlled feedback, and four iterative surveys conducted between 21 August 2023 and 21 September 2023. The domains addressed in the Delphi process included the need for a position statement, challenges in sepsis management, considerations for diagnosis, patient management while awaiting an intensive care unit (ICU) bed, and treatment of sepsis and septic shock in RLS. Consensus was achieved when 70% or more of the task force members voted either for or against statements using a Likert scale or a multiple-choice question (MCQ). The Delphi process with 100% participation of Task Force members in all rounds, generated consensus in 32 statements (91%) from which 20 clinical practice statements were drafted for the management of sepsis in RLS. The clinical practice statements will complement the existing international guidelines for the management of sepsis and provide valuable insights into tailoring sepsis interventions in the context of RLS, contributing to the global discourse on sepsis management. Future international guidelines should address the management of sepsis in RLS. How to cite this article: Juneja D, Nasa P, Chanchalani G, Cherian A, Jagiasi BG, Javeri Y, et al. The Indian Society of Critical Care Medicine Position Statement on the Management of Sepsis in Resource-limited Settings. Indian J Crit Care Med 2024;28(S2):S4-S19.

Clinical and epidemiological factors related to mortality due to septic shock in a pediatric intensive care unit.

INTRODUCTION: Septic shock is a potentially life-threatening condition. The aim of this study was to identify clinical and epidemiological factors associated with mortality in pediatric patients admitted to a pediatric intensive care unit (PICU) with septic shock. MATERIALS AND METHODS: A retrospective comparative case series study was conducted with children aged 1 month to 14 years with septic shock from 2018 to 2020 in a PICU in Lima, Peru. Patients were divided into deceased and survivor groups based on their condition at discharge from the PICU. The influence of each variable on mortality was assessed using a logistic regression model. RESULTS: A total of 174 patients were included in the study, with 51 (29.3%) fatalities. Deceased patients, compared to survivors, were older, had a higher incidence of oncological disease (31.4% vs. 14.6%; p = 0.011), more frequently presented with hemoglobin ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactate > 2 mmol/L (70% vs. 44%; p = 0.002), platelets ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001), and pH ≤ 7.1 (31% vs. 6%; p < 0.001). In the logistic regression model, factors related to mortality were having a pH ≤ 7.1 (odds ratio [OR] = 8.95; 95% confidence interval [CI]: 2.52-31.75) and platelets ≤ 150 (×103)/µL (OR = 3.89; 95% CI: 1.40-10.84). CONCLUSIONS: Factors associated with mortality in pediatric patients with septic shock were a pH ≤ 7.1 and platelets ≤ 150 (×103)/µL in the assessments conducted upon admission to the PICU.

INTRODUCCIÓN: El shock séptico es una condición potencialmente mortal. El objetivo del estudio fue identificar factores clínicos y epidemiológicos relacionados con la mortalidad en pacientes que ingresaron por shock séptico a una Unidad de Cuidados Intensivos Pediátricos (UCIP). MÉTODOS: Estudio retrospectivo tipo serie de casos comparativos con niños de 1 mes a 14 años hospitalizados por shock séptico del 2018 al 2020 en una UCIP de Lima en Perú. Los pacientes fueron divididos en fallecidos y vivos según su condición al alta de la Unidad. La influencia de cada variable sobre la mortalidad fue evaluada mediante un modelo de regresión logística. RESULTADOS: Ingresaron 174 pacientes al estudio, fallecieron 51 (29.3%). Los fallecidos en comparación con los vivos fueron de mayor edad, tuvieron más casos oncológicos (31.4% vs. 14.6%; p = 0.011), presentaron con mayor frecuencia hemoglobina ≤ 9 g/dL (44% vs. 28%; p = 0.043), lactato > 2 mmol/L (70% vs. 44%; p = 0.002), plaquetas ≤ 150 (×103)/µL (77% vs. 42%; p < 0.001) y pH ≤ 7,1 (31% vs. 6%; p < 0.001). En la regresión logística ajustada los factores que se relacionaron con la mortalidad fueron tener un pH ≤ 7,1 (OR = 8.95; IC 95%: 2.52 a 31.75) y plaquetas ≤ 150 (×103)/µL (OR = 3.89; IC 95%: 1.40 a 10.84). CONCLUSIONES: Los factores relacionados con la mortalidad en pacientes hospitalizados por shock séptico fueron tener un pH ≤ 7.1 y plaquetas ≤ 150 (×103)/µL en los controles realizados al ingreso de la UCIP.

Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study.

OBJECTIVE: The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI). METHODS: We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI. RESULTS: There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282-0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346-0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445-0.975; P = 0.037). CONCLUSION: The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function. Please cite this article as: Gong ZT, Yang HX, Zhu BB, Liu HH, Siri GL. Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study. J Integr Med. 2024; Epub ahead of print.

Phoenix criteria for sepsis: are these enough to guide a clinician?

Sepsis is the leading cause of mortality in children worldwide. There is a paucity of data on the criteria used to define sepsis and septic shock and predict mortality. Schlapbach et al. published Phoenix criteria to define sepsis in JAMA in 2024. Previously, paediatricians have used systemic inflammatory response syndrome (SIRS) criteria, but these criteria lack sensitivity and specificity. This group recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Though included in the 8-point criteria, important criteria like renal and liver are missing from the main criteria. We remain worried about the way these criteria got excluded from the main criteria. Therefore, in this brief report, whilst commending the authors for this stelar task, we highlight the main pitfalls in these criteria especially the renal, neurologic, and liver criteria. These criteria have been shown to be independently associated with outcomes, and we recommend that in the future iterations of the criteria, renal and liver criteria should be defined according to latest definitions and the task force consider utilizing latest criteria for each organ system involved within the formulated criteria. CONCLUSION:  In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. WHAT IS KNOWN: • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. WHAT IS NEW: • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

Exploration of different statistical approaches in the comparison of dopamine and norepinephrine in the treatment of shock: SOAP II.

BACKGROUND: Exploring clinical trial data using alternative methods may enhance original study's findings and provide new insights. The SOAP II trial has been published more than 10 years ago; but there is still some speculation that some patients may benefit from dopamine administration for shock management. We aimed to reanalyse the trial under different approaches and evaluate for heterogeneity in treatment effect (HTE). METHODS: All patients enrolled in SOAP II were eligible for reanalysis. We used a variety of methods including the win-ratio (WR), a Bayesian reanalysis stratified according to shock type, and both a risk-based and effect-based explorations for HTE. The methods were applied to different endpoints, including a hierarchy of death, new use of renal-replacement therapy (RRT), and new-onset arrhythmia; 28-day mortality; a composite endpoint (mortality, new use of RRT, and new-onset arrhythmia), and days alive and free of ICU at 28-days (DAFICU28). RESULTS: A total of 1679 patients were included (average age was 64.9 years, 57% male, 62% with septic and 17% with cardiogenic shock). All analysis favoured norepinephrine over dopamine. Under the WR approach, dopamine had fewer wins compared to norepinephrine (WR 0.79; 95% confidence intervals [CI] 0.68-0.92; p = 0.003), evident in both cardiogenic and septic shock subgroups. The Bayesian reanalysis for type of shock showed, for dopamine, a probability of harm of 0.95 for mortality, > 0.99 probability of harm for composite endpoint, and 0.91 probability of harm for DAFICU28. The fewer DAFICU28 with dopamine was more apparent in those with cardiogenic shock (0.92). Under the risk-based HTE, there was a high probability that dopamine resulted fewer DAFICU28 in the highest quartile of predicted mortality risk. The effect-based HTE assessment model did not recommended dopamine over norepinephrine for any combination of possible modifiers including age, type of shock, presence of cardiomyopathy, and SOFA score. Receiving dopamine when the effect-based model recommended norepinephrine was associated with an absolute increase in composite endpoint of 6%. CONCLUSION: The harm associated with the use of dopamine for the management of shock appears to be present in both septic and cardiogenic shock patients. There was no suggestion of any subgroup in which dopamine was found to be favourable over norepinephrine.

The use of pulmonary artery catheter and clinical outcomes in older adults with cardiogenic shock.

BACKGROUND: Evidence is lacking regarding the benefits of pulmonary artery catheter (PAC) for cardiogenic shock (CS). METHODS: We analyzed the data on Medicare fee-for-service beneficiaries aged 65-99 admitted with CS from 2016 to 2020 to compare outcomes of patients monitored with versus without PAC. We implemented propensity score matching weight (PSMW) analysis with hospital fixed effects (effectively comparing outcomes within the same hospital) and quasi-experimental instrumental variable (IV) analysis (accounting for potential unmeasured confounders) with the probability of using PAC for CS in the previous year as the instrument. RESULTS: We included 4668 and 78,502 patients admitted with CS, monitored with and without PAC, respectively. We found no evidence that the use of PAC was associated with mortality either in PSMW (adjusted absolute risk difference [aRD], +0.5-percentage-points [pp]; 95 % confidence interval [CI], -1.1 to +2.1) or IV (aRD, -2.5 pp.; 95 % CI, -8.2 to +3.2) analyses. While consistent associations were not observed between the use of PAC and major bleeding and sepsis, the use of PAC was associated with a higher risk of all-bleeding (PSMW: aRD, +1.5 pp.; 95 % CI, +0.1 to +2.9; IV: +13.3 pp.; 95 % CI, +7.7 to +18.8) and longer LOS (PSMW: adjusted mean difference, +1.6 days; 95 % CI, +1.1 to +2.0; IV: +6.9 days; +4.9 to +9.0). CONCLUSIONS: We found no evidence that the use of PAC was associated with lower mortality in patients with CS. While high-quality randomized trials are needed, providers should be careful about appropriate settings and indications of the use of PAC for the management of CS.

Impact of Inpatient Percutaneous Coronary Intervention Volume on 30-Day Readmissions After Acute Myocardial Infarction-Cardiogenic Shock.

BACKGROUND: There are limited data on volume-outcome relationships in acute myocardial infarction (AMI) with cardiogenic shock (CS). OBJECTIVES: In this study, the authors sought to evaluate the association between hospital percutaneous coronary intervention (PCI) volume and readmission after AMI-CS. METHODS: Adult AMI-CS patients were identified from the Nationwide Readmissions Database for 2016-2019 and were categorized into hospital quartiles (Q1 lowest volume to Q4 highest) based on annual inpatient PCI volume. Outcomes of interest included 30-day all-cause, cardiac, noncardiac, and heart-failure (HF) readmissions. RESULTS: There were 49,558 AMI-CS admissions at 3,954 PCI-performing hospitals. Median annual PCI volume was 174 (Q1-Q3: 70-316). Patients treated at Q1 hospitals were on average older, female, and with higher comorbidity burden. Patients at Q4 hospitals had higher rates of noncardiac organ dysfunction, complications, and use of cardiac support therapies. Overall, 30-day readmission rate was 18.5% (n = 9,179), of which cardiac, noncardiac, and HF readmissions constituted 56.2%, 43.8%, and 25.8%, respectively. From Q1 to Q4, there were no differences in 30-day all-cause (17.6%, 18.4%, 18.2%, 18.7%; P = 0.55), cardiac (10.9%, 11.0%, 10.6%, 10.2%; P = 0.29), and HF (5.0%, 4.8%, 4.8%, 4.8%; P = 0.99) readmissions. Noncardiac readmissions were noted more commonly in higher quartiles (6.7%, 7.4%, 7.7%, 8.5%; P = 0.001) but was not significant after multivariable adjustment. No relationship was noted between hospital PCI volume as a continuous variable and readmissions. CONCLUSIONS: In AMI-CS, there was no association between hospital annual PCI volume and 30-day readmissions despite higher acuity in the higher volume PCI centers suggestive of better care pathways for CS at higher volume centers.

GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba.

The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.

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.

BACKGROUND: Acute 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. RESULTS: Of 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). CONCLUSIONS: There 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.