[Fatal course of a fulminant gas gangrene of the right hemithorax]. / Letaler Verlauf eines fulminanten Gasgangräns des rechten Hemithorax.

The full clinical picture of a gas gangrene infection is an absolute rarity. The mechanism of development can be either traumatic or spontaneous (e.g., hematogenous seeding in occult colon carcinoma). In particular, the rare pathogen Clostridium septicum appears to be associated with spontaneously occurring gas gangrene. Diabetes mellitus is a significant risk factor. The mortality rate of the disease is around 50%, even with maximum therapeutic efforts, and the course of the disease is fulminant in the majority of cases. Initial symptoms are unspecific and make early diagnosis difficult. Treatment consists of high-dose antibiotics in combination with radical surgical debridement and, if necessary, supplementary hyperbaric oxygen therapy.

Walter Brendel and the dawn of transplantation research in Germany.

Walter Brendel was a physiologist who headed the Institut of Experimental Surgery at the University of Munich (LMU) from 1961 until 1989. His legendary career began with the development of an anti-human lymphocyte globulin (ALG) at his Institute during the late 1960s. The initial successful treatment of a small number of patients culminated in the co-treatment of the first successfully heart-transplanted patient in Capetown, South Africa (successful reversal with ALG of an acute allograft rejection). Walter Brendel was a pioneering personality whose work has laid a wide platform for the promotion of interdisciplinarily conducted innovative research programs in various domains of translational science and medicine. Among the many innovative achievements, the most notable are: discovery of involvement of the alternative pathway of complement activation in hyperacute xenograft rejection; induction of immunological tolerance to horse IgG as a means to prevent anaphylactic reactions during ALG therapy; development and clinical implementation of the extracorporeal shock wave lithotripsy for extracorporeal destruction of renal and ureteral calculi. The legacy of Brendel continues with the foundation of the Walter-Brendel Kolleg für Transplantationsmedizin (i.e., the German Transplant School for Transplantation Medicine), which has been held annually since 1994.

Prognostic Survey of ECPELLA in Japanese Patients With Acute Myocardial Infarction and Cardiogenic Shock　- Findings From the Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD).

BACKGROUND: The short-term mortality associated with veno-arterial extracorporeal membrane oxygenation combined with the Impella device (termed ECPELLA) for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) remains unclear. METHODS AND RESULTS: The Japanese Registry for Percutaneous Ventricular Assist Devices (J-PVAD) includes data on all patients treated with an Impella in Japan. We extracted data for 922 AMI-CS patients who underwent ECPELLA support and conducted an exploratory analysis focusing on 30-day mortality. The median age of patients was 69 years, and 83.8% were male. The overall 30-day mortality was 46.1%. Factors associated with mortality included age >80 years, in-hospital cardiac arrest, systolic blood pressure <90 mmHg, serum creatinine >1.5 mg/dL, and serum lactate >4.0 mmol/L. In patients aged >80 years with any of these factors, mortality was significantly higher than in those without, ranging from 57.5% to 64.9%. The J-PVAD score assigns 1 point per predictor, with a C-statistic of 0.620 (95% confidence interval 0.586-0.654). The 30-day mortality was 20.0% for a J-PVAD score of 0, increasing to 70.0% for a score of 5. CONCLUSIONS: The J-PVAD data indicate high short-term mortality in AMI-CS patients treated with ECPELLA, particularly among older patients. Further studies are needed to validate this risk stratification in this patient subset.

Prehospital Delta Shock Index Predicts Mortality and Need for Life Saving Interventions in Trauma Patients.

OBJECTIVES: The delta shock index (ΔSI), defined as the change in shock index (SI) over time, is associated with hospital morbidity and mortality, but prehospital studies about ΔSI are limited. We investigate the association of prehospital ΔSI with mortality and resource utilization, hypothesizing that increases in SI among field trauma patients are associated with increased mortality and blood product transfusion. METHODS: We performed a multicenter, retrospective, observational study from the Linking Investigators in Trauma and Emergency Services (LITES) network. We obtained data from January 2017 to June 2021. We fit logistic regression models to evaluate the association between an increase ΔSI > 0.1 and 28-day mortality and blood product transfusion within 4 hours of emergency department (ED) arrival. We used negative binomial models to evaluate the association between ΔSI > 0.1 and days in hospital, intensive care unit (ICU), and on ventilator (up to 28 days). RESULTS: We identified 33,219 prehospital patients. We excluded burn patients and those without documented prehospital or ED heart rate or blood pressure, resulting in 30,511 cases for analysis. In adjusted analysis for the primary outcome of 28-day mortality, patients who had a ΔSI > 0.1 based on initial vital signs were 31% more likely to die (adjusted odds ratio (AOR) of 1.31, 95% CI 1.21-1.41) compared to those patients who had a ΔSI ≤0.1. These patients also spent 16% more days in hospital (adjusted incident rate ratio (AIRR) 1.16, 95% CI 1.14-1.19), 34% more days in ICU (AIRR 1.34, 95% CI 1.28-1.41), and 61% more days on ventilator (ARR 1.61, 95% CI 1.47-1.75). Additionally, patients with a ΔSI > 0.1 had higher odds of receiving blood products (AOR 2.00, 95% CI 1.88-2.12) within 4 hours of ED arrival. Models fit excluding hypotensive patients performed similarly. CONCLUSIONS: An increase of greater than 0.1 in the ΔSI was associated with increased 28-day mortality; increased days in hospital, in ICU, and on ventilator; and increased need for blood product transfusion within 4 hours of ED arrival. This association held true for initially normotensive patients. Validation and implementation are needed to incorporate ΔSI into prehospital and ED triage.

Does younger children's social health insurance alleviate household impoverishment due to illness?

BACKGROUND: The ambitious expansion of social health insurance in China has played a crucial role in preventing and alleviating poverty caused by illness. However, there is no government-sponsored health insurance program specifically for younger children and inequities are more pronounced in healthcare utilization, medical expenditure, and satisfaction in some households with severely ill children. This study assessed the effectiveness of child health insurance in terms of alleviating poverty caused by illness. METHODS: Data were collected from two rounds of follow-up surveys using the China Family Panel Studies 2016 and 2018 child questionnaires to investigate the relationship between child health insurance and household medical impoverishment (MI). Impoverishing health expenditure (IHE) and catastrophic health expenditure (CHE) were measured to quantify "poverty due to illness" in terms of absolute and relative poverty, respectively. Propensity score matching with the difference-in-differences (PSM-DID) method, robustness tests, and heterogeneity analysis were conducted to address endogeneity issues. RESULTS: Social health insurance for children significantly reduced household impoverishment due to illness. Under the shock of illness, the incidences of IHE and CHE were significantly lower in households with insured children. The poverty alleviation mechanism transmitted by children enrolled in social health insurance was primarily driven by hospitalization reimbursements and the proportion of out-of-pocket medical payments among the total medical expenditure for children. CONCLUSIONS: Children's possession of social health insurance significantly reduced the likelihood of household poverty due to illness. The poverty-reducing effect of social medical insurance is most significant in rural areas, low-income families, no-left-behind children, and infants. Targeted poverty alleviation strategies for marginalized groups and areas would ensure the equity and efficiency of health system reforms, contributing to the goal of universal health insurance coverage in China.

BAP1 regulates HSF1 activity and cancer immunity in pancreatic cancer.

BACKGROUND: The vast majority of pancreatic cancers have been shown to be insensitive to single-agent immunotherapy. Exploring the mechanisms of immune resistance and implementing combination therapeutic strategies are crucial for PDAC patients to derive benefits from immunotherapy. Deletion of BAP1 occurs in approximately 27% of PDAC patients and is significantly correlated with poor prognosis, but the mechanism how BAP1-deletion compromises survival of patients with PDAC remain a puzzle. METHODS: Bap1 knock-out KPC (KrasG12D/+; LSLTrp53R172H/+; Pdx-1-Cre) mice and control KPC mice, syngeneic xenograft models were applied to analysis the correlation between BAP1 and immune therapy response in PDAC. Immunoprecipitation, RT-qPCR, luciferase and transcriptome analysis were combined to revealing potential mechanisms. Syngeneic xenograft models and flow cytometry were constructed to examine the efficacy of the inhibitor of SIRT1 and its synergistic effect with anti-PD-1 therapy. RESULT: The deletion of BAP1 contributes to the resistance to immunotherapy in PDAC, which is attributable to BAP1's suppression of the transcriptional activity of HSF1. Specifically, BAP1 competes with SIRT1 for binding to the K80 acetylated HSF1. The BAP1-HSF1 interaction preserves the acetylation of HSF1-K80 and promotes HSF1-HSP70 interaction, facilitating HSF1 oligomerization and detachment from the chromatin. Furthermore, we demonstrate that the targeted inhibition of SIRT1 reverses the immune insensitivity in BAP1 deficient PDAC mouse model. CONCLUSION: Our study elucidates an unrevealed mechanism by which BAP1 regulates immune therapy response in PDAC via HSF1 inhibition, and providing promising therapeutic strategies to address immune insensitivity in BAP1-deficient PDAC.

Non-acute myocardial infarction-associated cardiogenic shock in Hispanic patients: An analysis from the National Inpatient Sample Database.

Background: Current knowledge about non-acute myocardial infarction-associated cardiogenic shock (nAMI-CS) by ethnicity is limited. This study compares clinical features and outcomes of nAMI-CS in Hispanic versus non-Hispanic patients in the U.S. Methods: Hospitalizations with nAMI-CS from 2018 to 2020 were identified using the National Inpatient Sample (NIS) database. Patients were classified by ethnicity (Hispanic vs. non-Hispanic). Statistical analysis, including Chi-square and t-tests, was conducted using STATA version 18. Results: Out of 8607 nAMI-CS hospitalizations, 832 (9.6 %) were Hispanic. Hispanic patients were younger (62.3 ± 15.2 vs. 66.2 ± 15.3 years) and had higher incidences of smoking (2.4 % vs. 2.1 %), coronary artery disease (45.4 % vs. 44.1 %), myocardial infarction (2.9 % vs. 1.9 %), heart failure (10.1 % vs. 9.2 %), and diabetes mellitus (18.9 % vs. 18.1 %). They had lower incidences of hypertension (32.9 % vs. 34.3 %), valve disease (1.9 % vs. 2.1 %), and cerebrovascular disease (6.5 % vs. 8.5 %, all p < 0.005). Hispanic patients had slightly higher in-hospital mortality rates (18.6 % vs. 17 %, p < 0.001), with an adjusted odds ratio (aOR) of 1.20 (95 % CI: 1.01-1.50, p = 0.01). Their hospital stays were longer (17.7 ± 1.87 vs. 13.2 ± 0.31 days, p = 0.03) and costlier ($409,280 ± 591,582 vs. $291,298 ± 461,920, p = 0.03). Conclusion: Hispanic nAMI-CS patients are younger, have more co-morbid conditions, longer hospital stays, higher costs, and higher in-hospital mortality rates than non-Hispanic patients. Further research is needed to understand the mechanisms behind these disparities.

Sintilimab-induced myocarditis suspected in a patient with esophageal cancer and followed septic shock: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimab-associated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICI-induced cardiotoxicity is methylprednisolone. However, the long-term or high-dose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immune-mediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use.

Bladder inflation to reduce hemorrhage secondary to a pelvic fracture.

Bladder inflation may be a temporizing measure to tamponade pelvic bleeding in select trauma cases to bridge the patient to definitive interventions. Ultrasonographic confirmation of an intact bladder with an adjacent pelvic haematoma in a shocked adult with pelvic fracture is used for subject selection. An illustrative example of physiologic and interventional radiological control of pelvic bleeding following bladder inflation with sterile saline is presented.

Development and validation of a sepsis risk index supporting early identification of ICU-acquired sepsis: An observational study.

BACKGROUND: Sepsis is a threat to global health, and domestically is the major cause of in-hospital mortality. Due to increases in inpatient morbidity and mortality resulting from sepsis, healthcare providers (HCPs) would accrue significant benefits from identifying the syndrome early and treating it promptly and effectively. Prompt and effective detection, diagnosis, and treatment of sepsis requires frequent monitoring and assessment of patient vital signs and other relevant data present in the electronic health record. METHODS: This study explored the development of machine learning-based models to generate a novel sepsis risk index (SRI) which is an intuitive 0-100 marker that reflects the risk of a patient acquiring sepsis or septic shock and assists in timely diagnosis. Machine learning models were developed and validated using openly accessible critical care databases. The model was developed using a single database (from one institution) and validated on a separate database consisting of patient data collected across multiple ICUs. RESULTS: The developed model achieved an area under the receiver operating characteristic curve of 0.82 and 0.84 for the diagnosis of sepsis and septic shock, respectively, with a sensitivity and specificity of 79.1% [75.1, 82.7] and 73.3% [72.8, 73.8] for a sepsis diagnosis and 83.8% [80.8, 86.5] and 73.3% [72.8, 73.8] for a septic shock diagnosis. CONCLUSION: The SRI provides critical care HCPs with an intuitive quantitative measure related to the risk of a patient having or acquiring a life-threatening infection. Evaluation of the SRI over time may provide HCPs the ability to initiate protective interventions (e.g. targeted antibiotic therapy).

Synthesized V7 QRS Amplitude and Oversensing Episodes in Patients With Subcutaneous Implantable Cardioverter-Defibrillators.

BACKGROUND: Patients with subcutaneous implantable cardioverter-defibrillators (S-ICDs) experience an oversensing episode (OS) more frequently than those with transvenous ICDs. However, no established electrocardiography (ECG) parameters can accurately detect an OS. This study aimed to evaluate the incidence of an OS in real-world clinical practice and the association of synthesized 18-lead ECG (syn18-ECG) parameters with an OS. METHODS: We retrospectively included 21 consecutive patients who underwent S-ICD implantation and collected syn18-ECG parameters. We placed the generator in a deep posterior position and defined an OS as an inappropriate charging episode caused by cardiac or noncardiac signals. A SMART pass filter and two tachyarrhythmia zones were programed. RESULTS: The most frequent underlying heart disease was Brugada/J wave syndrome (n = 7). During a median follow-up period of 1188 days, an OS was observed in six patients (28.6%). The QRS amplitude in synthesized V7 lead (synV7) was significantly lower in the OS group than in the non-OS group (0.59 ± 0.17 vs. 0.91 ± 0.35 mV, p = 0.019). The optimal cutoff value of synV7 QRS amplitude was 0.61 mV, with a sensitivity of 80.0% and a specificity of 83.7% for predicting an OS. Univariate logistic analysis showed that a synV7 QRS amplitude of <0.61 mV was only associated with an OS (odd ratio, 20.0; 95% confidence interval, 1.66-241.72; p = 0.018). CONCLUSIONS: In patients with S-ICDs, an OS was not a rare complication during long-term follow-up. A low synV7 QRS amplitude was associated with a high OS incidence.

The molecular impact of sonoporation: A transcriptomic analysis of gene regulation profile.

Sonoporation has long been known to disrupt intracellular signaling, yet the involved molecules and pathways have not been identified with clarity. In this study, we employed whole transcriptome shotgun sequencing (RNA-seq) to profile sonoporation-induced gene responses after membrane resealing has taken place. Sonoporation was achieved by microbubble-mediated ultrasound (MB-US) exposure in the form of 1 MHz ultrasound pulsing (0.50 MPa peak negative pressure, 10 % duty cycle, 30 s exposure period) in the presence of microbubbles (1:1 cell-to-bubble ratio). Using propidium iodide (PI) and calcein respectively as cell viability and cytoplasmic uptake labels, post-exposure flow cytometry was performed to identify three viable cell populations: 1) unsonoporated cells, 2) sonoporated cells with low uptake, and 3) sonoporated cells with high uptake. Fluorescence-activated cell sorting was then conducted to separate the different groups followed by RNA-seq analysis of the gene expressions in each group of cells. We found that sonoporated cells with low or high calcein uptake showed high similarity in the gene responses, including the activation of multiple heat shock protein (HSP) genes and immediate early response genes mediating apoptosis and transcriptional regulation. In contrast, unsonoporated cells exhibited a more extensive gene expression alteration that included the activation of more HSP genes and the upregulation of diverse apoptotic mediators. Four oxidative stress-related and three immune-related genes were also differentially expressed in unsonoporated cells. Our results provided new information for understanding the intracellular mobilization in response to sonoporation at the molecular level, including the identification of new molecules in the sonoporation-induced apoptosis regulatory network. Our data also shed light on the innovative therapeutic strategy which could potentially leverage the responses of viable unsonoporated cells as a synergistic effector in the microenvironment to favor tumor treatment.

Differences in transcriptomic responses upon Phytophthora palmivora infection among cultivars reveal potential underlying resistant mechanisms in durian.

BACKGROUND: Phytophthora palmivora is a devastating oomycete pathogen in durian, one of the most economically important crops in Southeast Asia. The use of fungicides in Phytophthora management may not be a long-term solution because of emerging chemical resistance issues. It is crucial to develop Phytophthora-resistant durian cultivars, and information regarding the underlying resistance mechanisms is valuable for smart breeding programs. RESULTS: In this study, we conducted RNA sequencing (RNA-seq) to investigate early gene expression responses (at 8, 24, and 48 h) after the P. palmivora infection in three durian cultivars, which included one resistant cultivar (Puangmanee; PM) and two susceptible cultivars (Monthong; MT and Kradumthong; KD). We performed co-expression and differential gene expression analyses to capture gene expression patterns and identify the differentially expressed genes. The results showed that genes encoding heat shock proteins (HSPs) were upregulated in all infected durians. The expression levels of genes encoding HSPs, such as ERdj3B, were high only in infected PM. A higher level of P. palmivora resistance in PM appeared to be associated with higher expression levels of various genes encoding defense and chitin response proteins, such as lysM domain receptor-like kinases. MT had a lower resistance level than PM, although it possessed more upregulated genes during P. palmivora infection. Many photosynthetic and defense genes were upregulated in the infected MT, although their expression levels were lower than those in the infected PM. KD, the least resistant cultivar, showed downregulation of genes involved in cell wall organization or biogenesis during P. palmivora infection. CONCLUSIONS: Our results showed that the three durian cultivars exhibited significantly different gene expression patterns in response to P. palmivora infection. The upregulation of genes encoding HSPs was common in all studied durians. The high expression of genes encoding chitin response proteins likely contributed to P. palmivora resistance in durians. Durian susceptibility was associated with low basal expression of defense genes and downregulation of several cell wall-related genes. These findings enhance our understanding of durian resistance to Phytophthora infection and could be useful for the development of elite durian cultivars.

Avian malaria in a feral-pet pigeon: a case report.

BACKGROUND: Avian malaria is caused by diverse parasite species of the genus Plasmodium, and it affects various bird species. The occurrence of this disease in some wild bird species is sparsely documented due to the scarce availability of samples. Hence the pathogenicity in some hosts is not completely known. In addition, feral birds may act as reservoirs bridging the transmission cycle from wild migratory birds to domestic and zoo-kept bird species. CASE PRESENTATION: An owner of pigeons adopted a feral pigeon (Columba livia forma domestica) and housed it together with his other pet-pigeons. The bird died unexpectedly a few weeks after a surgical procedure and necropsy revealed a severely anaemic carcass, with pale organs and hydropericardium. Histopathologic analysis revealed inflammatory infiltrates in the lung and liver, and monocytes and Kupffer cells contained haemozoin pigment indicative of phagocytosis of Plasmodium-infected erythrocytes. A high erythrocytic infection rate of 18% was evident in tissues and blood vessels in various organs. Furthermore, the thyroid had masses classified as thyroid carcinomas. Immunohistochemistry with anti- Plasmodium falciparum HSP70 antibody revealed positive signals in erythrocytes and intravascular leucocytes. Further microscopy analysis using a Hemacolor-stained impression smear revealed a high parasitaemia with an asynchronous infection showing all erythrocytic stages. Molecular diagnosis by PCR identified Plasmodium relictum, lineage GRW11 as the aetiological agent. The bird presented died most likely due to an acute infection as evidenced by the high blood parasitaemia, leading to major erythrocyte destruction. Further analyses of feral pigeons (n = 22) did not reveal any additional cases of Plasmodium infections. CONCLUSION: This study reports the first mortality associated with P. relictum lineage GRW11. The study supports previous studies, suggesting that Plasmodium infections are not frequent in pigeons. Host conditions like immunosuppression due to the tumour may have influenced the infection outcome in this fatal case. Use of anti-P. falciparum HSP70 antibody for detection of P. relictum antigens for immune assays in blood and tissue samples will be a useful tool for future studies.

Peak tibial accelerations in different foot strike patterns during level running: an independent investigation in different cohorts.

Peak tibial accelerations are used to monitor impact severity during distance running and as input for bio-feedback. Here, peak tibial accelerations were compared between rearfoot and forefoot strikes. Two different studies were undertaken by independent research centres. Tibial acceleration and optical motion capture were collected in 14 rearfoot strikers who changed to a forefoot strike in the first centre. In the second centre, tibial acceleration of 14 other rearfoot strikers and nine forefoot strikers were collected and processed. In over-ground level running at a submaximal speed, the resultant peak tibial acceleration was greater in the instructed forefoot strike condition (ΔX = 7.6 ± 1.3 g, mean ± standard error difference) and in the habitual forefoot strikers (ΔX- = 3.7 ± 1.1 g) than in the rearfoot strikers. The shank kinematics revealed a greater decrease in antero-posterior velocity following touchdown in the forefoot strike condition. The forefoot strikes experienced greater posterior tibial acceleration, which resulted in an increased resultant peak tibial acceleration that also occurred earlier than in the rearfoot strikes. No significant difference in axial peak tibial acceleration was found between these foot strike patterns. In conclusion, the foot strike pattern differently affects peak tibial accelerations in level running, which can have implications for monitoring and biofeedback applications.

Fluid bolus resuscitation with hypertonic saline albumin solution in critically ill children: a prospective observational pilot study.

To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p < 0.05). Moreover, the amount of fluid requirements decreased significantly in the 6 h following HSA infusion [8.7 ml/kg (SD 9.6) vs. 15.1 ml/kg (SD 13.6) in the previous 6 h (p < 0.05)]. Serum levels of sodium and chloride increased after the infusion, reaching their peak concentration after one hour (143 mEq/L (SD 3.5) and 109.7 mEq/L (SD 6) respectively). HSA-related metabolic acidosis or acute kidney injury were not observed in this study. Hypertonic saline albumin is safe and effective when infused at a dose of 5 ml/kg in critically ill children. However, further research is required to confirm our findings.

Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

Pediatric Sepsis - Sailing the Unchartered Waters with Omics.

How to cite this article: Baalaaji M. Pediatric Sepsis - Sailing the Unchartered Waters with Omics. Indian J Crit Care Med 2024;28(9):818-819.

Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study.

Aim and background: Corticosteroids are recommended for use in adult patients with septic shock requiring vasopressors for blood pressure maintenance. However, this predisposes them to hyperglycemia, which is associated with a poor outcome. This prospective randomized study compares the effect of continuous infusion with bolus hydrocortisone on blood glucose levels in septic shock. Materials and methods: Forty adult patients with sepsis and septic shock requiring vasopressor support were randomly allocated to either group C (continuous infusion of hydrocortisone 200 mg/day) or group B (intermittent bolus dose of hydrocortisone 50 mg IV 6 hourly). Blood glucose level (primary objective), number of hyperglycemic and hypoglycemic episodes, daily insulin requirement, shock reversal incidence, time to shock reversal, and nursing workload required to maintain blood glucose within the target range (82-180 mg/dL) were compared. Results: The mean blood glucose level was comparable in the two groups (136.5 ± 22.08 mg/dL in group C vs 135.85 ± 19.06 mg/dL in group B; p = 0.921). The number of hyperglycemic and hypoglycemic episodes (p = 1.000 each), insulin requirement/day (p = 1.000), and nursing workload (p = 0.751) were also comparable among groups. Shock reversal was seen in 7/20 (35%) patients in continuous group and 12/20 (60%) patients in bolus group (p = 0.113). Time to shock reversal (p = 0.917) and duration of ICU stay (p = 0.751) were also statistically comparable. Conclusion: Both the regimes of hydrocortisone, continuous infusion, and bolus dose, have comparable effects on blood glucose levels in patients with septic shock.The study was registered prospectively with ctri.nic.in (Ref. No. CTRI/2021/01/030342; registered on 8/1/2021). How to cite this article: Salhotra R, Sharahudeen A, Tyagi A, Rautela RS, Kemprai R. Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study. Indian J Crit Care Med 2024;28(9):837-841.

Hydrocortisone for Septic Shock, Bolus or Infusion: Pro, Con, May be.

How to cite this article: Todi S. Hydrocortisone for Septic Shock, Bolus or Infusion: Pro, Con, May be. Indian J Crit Care Med 2024;28(9):816-817.