Expression of STAT3 and hypoxia markers in long-term surviving malignant glioma patients.

BACKGROUND: Glioblastoma is a malignant and aggressive type of central nevous system malignancy characterized by many distinct biological features including extensive hypoxia. Hypoxia in glioblatoma associates with complex signaling patterns including activation of several pathways such as MAPK, PI3K-AKT/mTOR and IL-6/JAK/STAT3 with the master regulator HIF-1, which in turn drive particular tumor behaviors determining, in the end, treatment outcomes and patients fate. Thus, the present study was designed to investigate the expression of selected hypoxia related factors including STAT3 in a small set of long-term surviving glioma patients. METHODS: The expression of selected hypoxia related factors including STAT3 was evaluated in a time series of formalin fixed paraffin embedded and cryopreserved glioma samples from repeatedly resected patients. In addition, comparative studies were also conducted on primary glioma cells derived from original patient samples, stabilized glioma cell lines and tumor-xenograft mice model. Obtained data were correlated with clinical findings too. RESULTS: Glioblastoma samples of the analyzed patients displayed heterogeneity in the expression of hypoxia- related and EMT markers with most interesting trend being observed in pSTAT3. This heterogeneity was subsequently confirmed in other employed models (primocultures derived from glioblastoma tissue resections, cryopreserved tumor specimens, stabilized glioblastoma cell line in vitro and in vivo) and concerned, in particular, STAT3 expression which remained stable. In addition, subsequent studies on the role of STAT3 in the context of glioblastoma hypoxia demonstrated opposing effects of its deletion on cell viability as well as the expression of hypoxia and EMT markers. CONCLUSIONS: Our results suport the importance of STAT3 expression and activity in the context of hypoxia in malignant glioblastoma long-term surviving glioma patients while emphasizing heterogeneity of biological outcomes in varying employed tumor models.

Length of hospital stay and factors associated with very-low-birth-weight preterm neonates surviving to discharge a cross-sectional study, 2022.

BACKGROUND: The length of hospital stay of very-low-birth-weight neonates (birth weight < 1500 g) depends on multiple factors. Numerous factors have been reported to influence the length of hospital stay (LOS). The objective of this study was to identify the length of hospital stay and associated factors among very-low-birth-weight preterm neonates. METHOD: A hospital-based, cross-sectional study was conducted. Data was collected using a pretested, structured questionnaire from April 1 to November 30, 2022. The data was entered using Epidata and Stata version 15.1. The frequencies, mean, median, and interquartile range were used to describe the study population about relevant variables. A linear regression model was used to see the effect of independent variables on dependent variables. RESULT: About 110 very low-birth-weight preterm neonates who survived to discharge were included in the study. The median birth weight was 1370 g, with an IQR of 1250-1430. The mean gestational age was 32.30 ± 1.79 weeks. The median length of hospital stay was 24 days, with an IQR of 13.5-40. The gestational age, type of initial management given, and presence of complications had a significant association with the length of hospital stay for VLBW preterm neonates. CONCLUSION: The median hospital stay was 24 days. The gestational age, presence of complications, and type of initial management given were associated with LOS for VLBW preterm neonates. The length of the hospital stay of the VLBW preterm neonates can be reduced by applying the standards of care of very-low-birth-weight preterm neonates.

Supporting Bereaved Family Members: A Qualitative Interview Study on the Experience of Bereavement Counselling by the Bereavement Network Lower Saxony (BNLS) in Germany for Parents Who Have Lost Children or Teenagers.

The "Trauer Netzwerk Niedersachsen" ("Bereavement Network Lower Saxony" (BNLS)) aims at supporting families after the loss of a child or teenager due to various causes. This study aims to describe the experiences of bereaved family members with the BNLS counsellors. 12 semi-structured interviews were conducted with parents who had received or were currently receiving BNLS counselling. The interviews revealed the vital role counselling played aiding individuals cope with their grief. Participants valued the bereavement support, which was often lacking in their personal support networks. Counselling assisted parents in returning to daily life and caring for loved ones. Discussing "death" and "dying" helped participants find peace with their loss. Our findings suggest that bereavement counselling should be considered an essential component of healthcare for family members dealing with the loss of a child. Additionally, there is need for awareness and publicity for both the BNLS and its bereavement counselling services.

Risk of Misleading Conclusions in Observational Studies of Time-to-Antibiotics and Mortality in Suspected Sepsis.

BACKGROUND: Influential studies conclude that each hour until antibiotics increases mortality in sepsis. However, these analyses often (1) adjusted for limited covariates, (2) included patients with long delays until antibiotics, (3) combined sepsis and septic shock, and (4) used linear models presuming each hour delay has equal impact. We evaluated the effect of these analytic choices on associations between time-to-antibiotics and mortality. METHODS: We retrospectively identified 104 248 adults admitted to 5 hospitals from 2015-2022 with suspected infection (blood culture collection and intravenous antibiotics ≤24 h of arrival), including 25 990 with suspected septic shock and 23 619 with sepsis without shock. We used multivariable regression to calculate associations between time-to-antibiotics and in-hospital mortality under successively broader confounding-adjustment, shorter maximum time-to-antibiotic intervals, stratification by illness severity, and removing assumptions of linear hourly associations. RESULTS: Changing covariates, maximum time-to-antibiotics, and severity stratification altered the magnitude, direction, and significance of observed associations between time-to-antibiotics and mortality. In a fully adjusted model of patients treated ≤6 hours, each hour was associated with higher mortality for septic shock (adjusted odds ratio [aOR]: 1.07; 95% CI: 1.04-1.11) but not sepsis without shock (aOR: 1.03; .98-1.09) or suspected infection alone (aOR: .99; .94-1.05). Modeling each hour separately confirmed that every hour of delay was associated with increased mortality for septic shock, but only delays >6 hours were associated with higher mortality for sepsis without shock. CONCLUSIONS: Associations between time-to-antibiotics and mortality in sepsis are highly sensitive to analytic choices. Failure to adequately address these issues can generate misleading conclusions.

Signatures of adaptive decreased virulence of deformed wing virus in an isolated population of wild honeybees (Apis mellifera).

Understanding the ecological and evolutionary processes that drive host-pathogen interactions is critical for combating epidemics and conserving species. The Varroa destructor mite and deformed wing virus (DWV) are two synergistic threats to Western honeybee (Apis mellifera) populations across the globe. Distinct honeybee populations have been found to self-sustain despite Varroa infestations, including colonies within the Arnot Forest outside Ithaca, NY, USA. We hypothesized that in these bee populations, DWV has been selected to produce an avirulent infection phenotype, allowing for the persistence of both host and disease-causing agents. To investigate this, we assessed the titre of viruses in bees from the Arnot Forest and managed apiaries, and assessed genomic variation and virulence differences between DWV isolates. Across groups, we found viral abundance was similar, but DWV genotypes were distinct. We also found that infections with isolates from the Arnot Forest resulted in higher survival and lower rates of symptomatic deformed wings, compared to analogous isolates from managed colonies, providing preliminary evidence to support the hypothesis of adaptive decreased viral virulence. Overall, this multi-level investigation of virus genotype and phenotype indicates that host ecological context can be a significant driver of viral evolution and host-pathogen interactions in honeybees.

The impact of a sepsis performance improvement program in the emergency department: a before-after intervention study.

PURPOSE: The latest Surviving Sepsis Campaign guidelines advocate that all hospitals use sepsis performance improvement programs. However, there is a limited evidence about how to structure such programs and what their potential impact is on sepsis management and outcomes in the emergency department (ED). In this study, we evaluated the implementation of a sepsis performance improvement program in the ED including a dedicated sepsis response team and analyzed the management and outcomes of sepsis patients before and after. METHODS: We conducted a before-after interventional study in the ED of the Amsterdam University Medical Centers, the Netherlands. The sepsis performance improvement program included regular educational meetings, daily audits and weekly feedback, a screening tool, and a dedicated multidisciplinary sepsis response team. We studied all adult patients who presented to the ED with a suspected infection and a Modified Early Warning Score (MEWS) ≥ 3 during their stay. In the postintervention phase, these patients were seen by the sepsis team. Process-related and patient-related outcomes were measured between November 2019 and February 2020 (preintervention) and December 2021-May 2022 (postintervention). RESULTS: A total of 265 patients were included in the primary study, 132 patients preintervention and 133 patients postintervention. The postintervention phase was associated with improvements in nearly all process-related outcomes, such as a shorter time to antibiotics (66 vs. 143 min; p < 0.001), increased number of lactate measurements (72.9 vs. 46.2%; p < 0.001), and improved completeness of documented MEWS scores (85.0 vs. 62.9%; p < 0.001). Except for an improvement in the number of immediate versus delayed ICU admissions (100% immediate vs. 64.3% immediate; p = 0.012), there was no improvement in the other patient-related outcomes such as 28 days mortality (14.3 vs. 9.1%; p = 0.261), during the postintervention phase. CONCLUSION: Our program stimulated physicians to make timely decisions regarding diagnostics and treatment of sepsis in the ED. Implementing the sepsis performance improvement program was associated with significant improvements in most process-related outcomes but with minimal improvements in patient-related outcomes in our cohort.

[Transfer rates of the Psychiatric and Neurological University Hospital in Frankfurt am Main during National Socialism]. / Verlegungsraten der Universitätsnervenklinik Frankfurt am Main im Nationalsozialismus.

During the era of National Socialism around 300,000 people were murdered in the "euthanasia" programs. The majority of those killings took place in asylums, whereas no killings in psychiatric and neurological university (PNU) hospitals have so far been identified. Furthermore, there were no deportations from these hospitals to the gassing asylums. Nevertheless, the PNUs took part in the "euthanasia" by transferring patients to asylums, where many of them were either killed or deported to gassing asylums. There are only a few studies that empirically describe these transfers. In this study the rates of transfers of the PNU Frankfurt am Main are reported for the first time, thus allowing a judgment of the involvement in the "euthanasia" programs. The rate of patients transferred to asylums dropped from 22-25% in the years before to around 16% in the years after knowledge about the mass killings in the asylums spread in the PNU Frankfurt. Of the patients transferred between 1940 and 1945, 53% died in the asylums before 1946. The high mortality rate of the transferred patients underlines that the role of the PNUs in the "euthanasia" programs should be examined in more detail.

CATHETER DIRECTED THROMBOLYSIS IN ACUTE LIMB ISCHEMIA PATIENTS. A SINGLE CENTER'S EXPERIENCE.

OBJECTIVE: The aim: This study evaluates catheter-directed thrombolysis (CDT) outcomes in patients with acute lower limb arterial thrombosis and acute limb ischemia. PATIENTS AND METHODS: Materials and methods: 53 patients (17 females, 36 males, aged 53-76) were studied. 57% had femoropopliteal and below-the-knee (BTK) thromboocclusion, 43% had BTK thromboocclusion. Symptoms included pain, pallor, edema, and cyanosis. Exclusions criteria: contracture, recent surgeries, bleeding. RESULTS: Results: In 29 (97%) patients regression of lower-limb ischemia rate by 1-2 stages according to the Rutherford classification were observed. One patient (3%) did not exhibit any regression in the degree of lower-limb ischemia, experiencing increasing pain and decreased sensitivity in the lower limb, leading to the development of contracture in the ankle joint and subsequent lower limb amputation over 7 days. Among 12 (40%) patients, after performing follow-up arteriography of the lower limb, angioplasty was performed on the diagnosed steno-occlusive lesions in the revascularized segment with secondary angioplasty. Within a year, one (3%) patient experienced recurrent thrombosis of the lower limb arteries with subsequent revascularization. CONCLUSION: Conclusions: CDT is recommended for ALI Patients with arterial thrombooclusion.

Elevated Levels of Three Reactive Oxygen Species and Fe(II) in the Antibiotic-Surviving Population of Mycobacteria Facilitate De Novo Emergence of Genetic Resisters to Antibiotics.

We had earlier reported the de novo emergence of genetic resisters of Mycobacterium tuberculosis and Mycobacterium smegmatis to rifampicin and moxifloxacin from the antibiotic-surviving population containing elevated levels of the non-DNA-specific mutagenic reactive oxygen species (ROS) hydroxyl radical. Since hydroxyl radical is generated by Fenton reaction between Fe(II) and H2O2, which is produced by superoxide dismutation, we here report significantly elevated levels of these three ROS and Fe(II) in the M. smegmatis rifampicin-surviving population. Elevated levels of superoxide and the consequential formation of high levels of H2O2 and Fe(II) led to the generation of hydroxyl radical, facilitating de novo high frequency emergence of antibiotic resisters. The M. smegmatis cultures, exposed to nontoxic concentrations of the ROS scavenger, thiourea (TU), and the NADH oxidase (one of the superoxide producers) inhibitor, diphenyleneiodonium chloride (DPI), showed a reduction in the levels of the three ROS, Fe(II), and antibiotic resister generation frequency. The non-antibiotic-exposed cultures grown in the absence/presence of TU/DPI did not show increased ROS, Fe(II) levels, or antibiotic resister generation frequency. The antibiotic-surviving population showed significantly increased expression and activity of superoxide-producing genes and decreased expression of antioxidant and DNA repair genes, revealing an environment conducive for the acquisition and retention of mutations. Since we recently reported significant comparability between the antibiotic-survival gene expression profiles of the saprophyte-cum-opportunistic pathogens M. smegmatis and the M. tuberculosis in tuberculosis patients undergoing treatment, we discuss the clinical relevance of the findings on the mechanism of emergence of antibiotic-resistant mycobacterial strains.

Surviving early career research and beyond in biophysics/biological physics: a concise user guide.

Early career researcher (ECR) development is a dynamic challenge that tensions the urge to perform ground-breaking research against an ultimate practical aspiration of establishing an acceptable level of job security. There is no typical career path for an ECR, least of all in the area of biophysics/biological physics. Being explicitly interdisciplinary across the physical-life sciences interface presents more opportunities for a multiplicity of career trajectories through different home academic institutions and departments, as well as offering a broader range of alternative future career trajectories in non-academic sectors. That said, there are key common features, such as the transient nature of fixed-term postdoctoral contracts, the substantial research and domestic challenges that these present, and the often overwhelming pressures of the realities of competition in the job market. In this short article, I outline the key challenges to ECRs in this area and discuss simple strategies to manage and potentially overcome them. To highlight discussion, I draw from specific exemplars in the UK, however, the key guide applies globally to all ECRs in biophysics/biological physics.

Relationship between time of emergency department admission and adherence to the Surviving Sepsis Campaign bundle in patients with septic shock.

BACKGROUND: Nighttime hospital admission is often associated with increased mortality risk in various diseases. This study investigated compliance rates with the Surviving Sepsis Campaign (SSC) 3-h bundle for daytime and nighttime emergency department (ED) admissions and the clinical impact of compliance on mortality in patients with septic shock. METHODS: We conducted an observational study using data from a prospective, multicenter registry for septic shock provided by the Korean Shock Society from 11 institutions from November 2015 to December 2017. The outcome was the compliance rate with the SSC 3-h bundle according to the time of arrival in the ED. RESULTS: A total of 2049 patients were enrolled. Compared with daytime admission, nighttime admission was associated with higher compliance with the administration of antibiotics within 3 h (adjusted odds ratio (adjOR), 1.326; 95% confidence interval (95% CI), 1.088-1.617, p = 0.005) and with the complete SSC bundle (adjOR, 1.368; 95% CI, 1.115-1.678; p = 0.003), likely to result from the increased volume of all patients and sepsis patients admitted during daytime hours. The hazard ratios of the completion of SSC bundle for 28-day mortality and in-hospital mortality were 0.750 (95% CI 0.590-0.952, p = 0.018) and 0.714 (95% CI 0.564-0.904, p = 0.005), respectively. CONCLUSION: Septic shock patients admitted to the ED during the daytime exhibited lower sepsis bundle compliance than those admitted at night. Both the higher number of admitted patients and the higher patients to medical staff ratio during daytime may be factors that are responsible for lowering the compliance.

Temporal trends in the epidemiology, management, and outcome of sepsis-A nationwide observational study.

BACKGROUND: Registry-based studies have shown increasing incidence of sepsis and declining mortality rates in recent years, but are inherently at risk of bias. The objectives of this study were to describe 11-year trends in the incidence, treatment and outcome of sepsis using clinical criteria with chart review. METHODS: This was a retrospective, observational study. All adult admissions to Icelandic ICUs during years 2006, 2008, 2010, 2012, 2014, and 2016 were screened for severe sepsis or septic shock by ACCP/SCCM criteria (sepsis-2). Incidence, patient characteristics, treatment and outcome were compared across the study years. RESULTS: During the six study years, 9166 patients were admitted to Icelandic ICUs, 971 (10.6%) because of severe sepsis or septic shock. The crude incidence of sepsis requiring admission to ICU remained stable between 0.55 and 0.75 per 1000 inhabitants. No statistically significant trends were observed over time in median patient age (67 years), APACHE II score (21), SOFA score (8) or Charlson Comorbidity Index (4). The time to antibiotic administration (median 1.8 h) in the emergency departments was stable over the study period but the time to lactate measurements decreased from 4.1 h in 2006 to 1.2 h in 2016, p < .001. The 28-day mortality was 25% and 1-year mortality 41%, both with no observed change with time. CONCLUSIONS: In a nationwide cohort, diagnosed with clinical criteria, the incidence of sepsis requiring intensive care did not change over an 11-year period. Mortality remained stable and only minimal changes were observed in initial resuscitation in the emergency departments.

Risk factors and Compliance of surviving sepsis campaign: A retrospective cohort study at tertiary care hospital.

BACKGROUND AND OBJECTIVE: Sepsis is one of the leading causes of direct maternal mortality in Pakistan. It is recommended that the first three hours after the presentation are crucial. During this time implementation of surviving sepsis campaign resuscitation bundles reduces maternal mortality. Our objective was to assess the factors contributing to puerperal sepsis and the compliance of "surviving sepsis campaign resuscitation bundles in puerperal sepsis" for the management of puerperal sepsis. METHODS: This was a retrospective record review for five years from January 2011-December 2015. All women who fulfilled the inclusion criteria of puerperal sepsis were included and data from their files were collected and entered in SPSS version 19.0. Mean and standard deviations were calculated for continuous variables while for categorical variable proportion and percentages were used. RESULTS: This retrospective record review in five years showed the 396 patients had P-sepsis, among them 44 patients had severe sepsis with organ dysfunction. The culture was positive in 26(59%) with trend of E-coli in 9(20%) Among them 12(27%) had serum lactate more than ≥4mmol/L. Central venous pressure monitoring with fluid resuscitation was done as per protocol of survival bundle given to all 12(100%), Vasopressin was needed in half of these patients 6(50%). Amid 44 patients of severe sepsis 29(66%) were admitted to special care, while 15(34%) required intensive care admissions. Our 7(16%) patients failed to survive. All of them had multi-organ failure. CONCLUSION: There was moderate adherence of modified surviving sepsis campaign resuscitation bundles. Further improvement in compliance is warranted.

Viewpoint: Weak Scientific Basis for the Recommendation of Executive Summary of Surviving Sepsis Campaign Guidelines 2021.

The Executive summary of Sepsis 2021 was published recently, which for the first time, recommended that in septic shock, the vasopressor infusion should be commenced through a peripherally inserted venous catheter (PiVC) for up to 6 hours. We discuss the scientific basis for such a recommendation regarding the safety of vasopressor infusion through a peripherally inserted vascular catheter or the accepted duration. How to cite this article: Nath SS, Nachimuthu N. Viewpoint: Weak Scientific Basis for the Recommendation of Executive Summary of Surviving Sepsis Campaign Guidelines 2021. Indian J Crit Care Med 2022;26(8):898-899.

Aggressive versus conservative fluid resuscitation in septic hemodialysis patients.

PURPOSE: Sepsis and bacterial infections are common in patients with end-stage renal disease (ESRD). We aimed to compare patients with ESRD on hemodialysis presenting to hospital with severe sepsis or septic shock who received <20 ml/kg of intravenous fluid to those who received ≥20 ml/kg during initial resuscitation. MATERIALS AND METHODS: We conducted a retrospective chart review of adult patients with ICD codes for discharge diagnosis of sepsis, severe sepsis, septic shock, ESRD, and hemodialysis admitted to our institution between 2015 and 2018. RESULTS: We present outcomes for a total of 104 patients - 51 patients in conservative group and 53 in aggressive group. The mean age was 69.5 ± 11.2 years and 71 ± 11.5 years in the conservative group and aggressive group, respectively. There was no significant difference in the rate of ICU admission, and ICU or hospital length of stay between the two groups. Complications such as volume overload, rate of intubation, and urgent dialysis were not found to be significantly different. CONCLUSION: We found that aggressive fluid resuscitation with ≥20 ml/kg may not be detrimental in the initial resuscitation of ESRD patients with SeS or SS. However, a clinical decision of volume responsiveness should be made on a case-by-case basis rather than a universal approach for fluid resuscitation in ESRD patients.

Imaging diagnosis and legal implications of brain injury in survivors following single intrauterine fetal demise from monochorionic twins - a review of the literature.

Brain injury of the surviving twin from monochorionic pregnancies following intrauterine fetal demise during the second and third trimesters is a rare but severe complication. Monochorionicity and gestational age at the time of stillbirth seem to be decisive factors in terms of long-term neurologic outcome prediction for the survivor. Magnetic resonance imaging (MRI), diffusion weighted imaging (DWI) in particular, seem to bring the earliest and most accurate diagnosis. Ultrasound detection of brain damage is possible in later stages of fetal brain injury. It is essential to provide early diagnosis and multidisciplinary counsel to the parents to ensure informed decision making. For couples who choose to terminate pregnancy legislation related to late abortion might lead to further distress. Our paper aims to stress the importance of MRI DWI in the evaluation of surviving twins following single intrauterine fetal demise in monochorionic pregnancies and the delicate context of the medical professionals and parents facing this clinical situation, sometimes complicated by legal constraints.

Moringa oleifera ethanolic extract ameliorates the testicular dysfunction resulted from HFD-induced obesity rat model.

In this study, we estimated the protective role of Moringa oleifera leaf ethanolic extract (MOLE) against obesity-associated testicular dysfunction. Fifty male albino rats were randomly assigned to five groups (n = 10): Group I (basal diet), group II (basal diet plus MOLE orally), group III (high-fat diet-HFD), group IV (HFD plus oral MOLE) and group V (HFD for 8 weeks followed by a basal diet plus oral MOLE for 6 weeks). The study duration extended for 14 weeks. Serum collected to investigate testosterone, FSH and LH levels. Testicular tissues were used to determine levels of SOD, glutathione, catalase and malondialdehyde. Semen was collected to estimate its quality (morphology, motility and concentration). Morphological changes in the testis were investigated by histopathological and immunohistochemical techniques. Compared with both control treatment and MOLE treatment, serum testosterone, FSH, LH, testicular enzymatic catalase, SOD, GSH, survivin immunoreactivity, sperm quality and testicular weight were all significantly decreased in rats treated with HFD, while there were significant increases in testicular malondialdehyde and caspase-3 immunoreactivity. MOLE improved all harmful effects of HFD. Improvements were more pronounced in the protected (G 4) than the treated (G 5) group. MOLE could be a potential solution for obesity-associated fertility problem.

Sarcomas of the Larynx: One Institution's Experience and Treatment Protocol Analyses.

Soft tissue sarcomas in the head and neck are rare malignancies. They occur in this area in less than 1% of all malignant tumors. Some authors have described the development of sarcoma from the mesenchymal tissue in the larynx. The histological diagnosis of a sarcoma depends on the immunohistochemical investigation. In particularly difficult diagnoses, electron microscopy has to be used. The treatment recommendation depends on the histological type of sarcoma. We analysed and summarized data on the diagnostic criteria and therapy for sarcoma of the larynx presented in the literature. We present three new cases of laryngeal sarcoma and describe the analyses of the published diagnostic and treatment schedules of laryngeal sarcomas. We developed a treatment protocol recommendation for laryngeal sarcoma based on an analysis of literature data and case reports. This recommendation is based on histological type, staging, grading, size, and survival data.

The Phenomenon of Bereaved Parenting: An Integrative Review of Literature.

Bereaved parenting, a role that entails parenting surviving children after experiencing the death of a child, is a unique but understudied phenomenon within bereavement research. Not much is known about the impact of a child's death on this crucial familial role. An integrative review of literature of 20 studies across psychology, nursing, communications, social work, and family sciences was undertaken to determine the current state of science regarding bereaved parenting. Results revealed three influential contexts: the general context of parental grief and bereavement, described as traumatic and life-changing experiences; the personal context of the resulting parental changes and coping strategies; and the relational context of the subsequent parenting of surviving children, an experience characterized by periodic conflict between personal and children's needs, emotional fluctuations, challenges with levels of protectiveness and control, and a heightened sense of responsibility within the parental role. Discussion of results and implications for research are presented.

How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines.

OBJECTIVES: "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016" provides guidelines in regard to prompt management and resuscitation of sepsis or septic shock. The study is aimed to assess the robustness of randomized controlled trials (RCTs) that formulate these guidelines in terms of fragility index and reverse fragility index. METHOD: RCTs that contributed to these guidelines having parallel two-group design, 1:1 allocation ratio, and at least one dichotomous outcome were included in the study. The median fragility index was calculated for RCTs with significant statistical outcomes, whereas the median reverse fragility index was calculated for RCTs with nonsignificant statistical results. RESULTS: Hundred RCTs that met the inclusion criteria were analyzed. The median fragility index was 5.5 [95% confidence interval (CI) 1-30] and median reverse fragility index was 13 (95% CI 12.07-16.8) at a p value of 0.05. The median reverse fragility index was 16 (95% CI 10-26) at a p value of 0.01. Most of the RCTs included in this analysis were of good quality, having a median Jadad score of 6. CONCLUSION: This analysis found that the surviving sepsis guidelines were based on highly robust RCTs with statistically insignificant results and on some moderately robust RCTs with statistically significant results. RCTs with statistically insignificant results were more robust than RCTs with statistically significant results in regard to these guidelines. HIGHLIGHTS: The study assessed the robustness of randomized controlled trials (RCTs) that were used to formulate surviving sepsis guidelines. Most RCTs showed statistically nonsignificant results. RCTs with statistically significant results were moderately fragile whereas RCTs with nonsignificant results were more robust. HOW TO CITE THIS ARTICLE: Choupoo NS, Das SK, Saikia P, Dey S, Ray S. How Robust are the Evidences that Formulate Surviving Sepsis Guidelines? An Analysis of Fragility and Reverse Fragility of Randomized Controlled Trials that were Referred in these Guidelines. Indian J Crit Care Med 2021;25(7):773-779.