Environmental Risk Analysis: Problems and Perspectives in Different Countries

The authors discuss various industrial accidents, which have led to growing concerns about the potential hazards and risks involved in chemical process industries

Colistin for lung infection: an update

Increasing incidence of resistance of gram-negative bacteria against even newer antibiotic including carbapenem has generated interest in the old antibiotic colistin, which are being used as salvage therapy in the treatment of multidrug resistant infection. Colistin has excellent bactericidal activity against most gram-negative bacilli. It has shown persist level in the liver, kidney, heart, and muscle; while it is poorly distributed to the bones, cerebrospinal fluid, lung parenchyma, and pleural cavity. Being an old drug, colistin was never gone through the drug development process needed for compliance with competent regulatory authorities that resulted in very much limited understanding of pharmacokinetic (PK) and pharmacodynamic (PD) parameters, such as C(max)/MIC ratio, AUC/MIC and T > MIC that could predict the efficacy of colistin. In available PK/PD studies of colistin, mean maximum serum concentration (C(max)) of colistin were found just above the MIC breakpoint at steady states that would most probably lead to suboptimal for killing the bacteria, even at dosages of 3.0 million international units (MIU) i.e., 240 mg of colistimethate sodium (CMS) intravenously every 8 h. These finding stresses to use high loading as well as high maintenance dose of intravenous colistin. It is not only suboptimal plasma concentration of colistin but also poor lung tissue concentration, which has been demonstrated in recent studies, poses major concern in using intravenous colistin. Combination therapy mainly with carbapenems shows synergistic effect. In recent studies, inhaled colistin has been found promising in treatment of lung infection due to MDR gram-negative bacteria. New evidence shows less toxicity than previously reported

Mortality, functional outcome and health-related quality of life in patients with necrotizing skin- and soft tissue infections in the ICU: Protocol of a multinational prospective cohort study (SKIN-ICU)

Adult intensive & critical care; Adult surgery; Necrotizing soft tissue infectionsCuidados intensivos y críticos para adultos; Cirugía de adultos; Infecciones necrosantes de tejidos blandosCures intensives i crítiques per a adults; Cirurgia d'adults; Infeccions necrotitzants de teixits tousBackground Necrotizing soft tissue infections (NSTI) are rare and life-threatening bacterial infections characterized by necrosis of subcutaneous tissue, fascia, or muscle. Few prospective studies have been conducted. The primary objective is to assess the 90-day mortality rate and to identify prognostic factors in patients with NSTI in an international setting. Secondary objectives are i) to characterize the clinical and microbiological presentation and management; ii) to assess the risk of limb amputation and associated factors; and iii) to assess functional and health-related quality of life (HRQoL) outcomes and associated factors. Methods We are conducting a multinational, prospective, non-interventional cohort study. We plan to enroll 1,033 consecutive patients admitted to 85 hospitals with surgically proven NSTI between November 2021 and December 2024 in 17 countries over three continents. Data will be collected prospectively on a secure web-based server. The primary outcome measure will be the day-90 mortality. Secondary outcomes include need for limb amputation, the activity of daily living scale and health-related quality of life at day-90 (EQ-5D-5L questionnaire). Baseline characteristics associated with outcomes will be identified by multivariable analyses. Exploratory analyses will be conducted to assess the impact of therapeutic interventions on day-90 mortality and secondary outcomes. The study protocol has been approved by an ethics committee in each participating country.This work was supported by the European Society of Intensive Care Medicine (ESICM) 2020 Next Start-up grant

Differential gene expression analysis in germinating and dormant teliospores of Tilletia indica using RNA seq approach

Karnal bunt of wheat is an important quarantine disease that interrupts India’s wheat trade in the international market. The whole transcriptome of germinating and dormant teliospores of Tilletia indica was performed using the RNA Seq approach to identify germination-related genes. Approximately 63 million reads were generated using the RNA sequencing by the Illumina NextSeq500 platform. The high-quality reads were deposited in NCBI SRA database (accession: PRJNA522347). The unigenes from the pooled teliospores were 16,575 having unigenes length of 28,998,753 bases. The high-quality reads of germinating teliospores mapped on to 21,505 predicted CDSs. 9,680 CDSs were common between dormant and germinating teliospores of T. indica. 11,825 CDSs were found to be in germinating teliospores while only 91 were unique in dormant spores of pathogen. The pathway analysis showed the highest number of pathways was found in germinating spores than dormant spores. The highest numbers of CDSs were found to be associated with translation (431 in number), transport and catabolism (340), signal transduction (326), and carbohydrate metabolism (283). The differential expression analysis (DESeq) of germinating and dormant teliospores showed that 686 CDS were up-regulated and 114 CDS were down-regulated in the germinating teliospores. Significant germination-related genes in the spores were validated using qPCR analysis. Ten genes viz. Ti3931, Ti6828, Ti7098, Ti7462, Ti7522, Ti 9289, Ti 8670, Ti 7959, Ti 7809,and Ti10095 were highly up-regulated in germinated teliospores which may have role in germination of spores.Further, these differentially expressed genes provide insights into the molecular events. This first study of transcriptome will be helpful to devise better management strategies to manage Karnal bunt disease

Right heart in septic shock: prospective observational study

BACKGROUND: The right heart often receives less attention during echocardiography. The situation is no different in septic shock. We prospectively investigated the echocardiographic indices of the right heart in septic shock adult patients. METHODS: Septic shock ICU patients within 24 h of admission were subjected to transthoracic echocardiography (TTE) as per the 2005 guidelines from the American Society of Echocardiography. RESULTS: Eighty-eight septic shock patients (M:F = 52:36) underwent TTE. Thirty-six patients survived. Significant differences in demographic and biochemical (laboratory and metabolic) parameters, severity scores, life-support therapies (vasopressors, ventilation), and length of ICU stay were observed between survivors and non-survivors. Right heart abnormalities of chamber dimension and systolic and diastolic function existed in 79, 25, and 86 % of patients, respectively. Right ventricle subcostal wall thickness (91 %), pulse Doppler myocardial performance index (73 %), and E/E′ (63 %) were the predominant abnormalities in chamber dimension, systolic function, and diastolic function of the right heart, respectively. However, the presence of these abnormalities did not signify poor survival in our study. CONCLUSIONS: Right heart dimensional and functional abnormalities exist in high proportions in septic shock. However, their predictability of poor outcomes remains questionable

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

A world-wide study on delirium assessments and presence of protocols

Acknowledgement of collaborative authors: The “WDAD Study Team” comprises of 158 non-author collaborators. They are listed in Appendix 1a in the Supplementary Data. The authors would like to gratefully acknowledge the many participating clinicians for supporting the 2023 WDAD Study Team and survey. They are named in Appendix 1b in the Supplementary Data.Peer reviewe

Multinational transfusion practices and outcomes in haematology patients admitted to the intensive care unit

Background and Objectives: The number of critically ill patients with haematological conditions is increasing, yet transfusion practices in this population remain poorly defined. This study aimed to compare transfusion strategies in critically ill patients with versus without haematological conditions. Study Design and Methods: This international, prospective observational substudy of the International Point Prevalence Study of Intensive Care Unit [ICU] Transfusion Practices (InPUT) evaluated transfusion use in ICU patients with and without haematological conditions, including benign or malignant diseases or a history of stem cell transplantation. Outcomes included use of red blood cells (RBCs), platelets, plasma, haemostatic interventions, transfusion indications and thresholds. Results: Of 3643 ICU patients, 131 (3.6%) had a haematological condition. These patients were more likely to receive RBC (odds ratio [OR] 1.58, 95% confidence interval [CI] 1.09–2.29) and platelet transfusions (OR 8.32, 95% CI 5.09–13.6), primarily due to low haemoglobin rather than physiological triggers. Platelet thresholds were lower (median 23 × 109/L vs. 64 × 109/L) compared to non‐haematology patients. Both platelet and plasma transfusions were more frequently administered prophylactically rather than for active bleeding. Haemostatic interventions were more often used in haematology patients, at higher doses and typically without viscoelastic testing. Transfused haematology patients had higher 28‐day mortality and longer ICU stays. Conclusion: ICU patients with haematological conditions receive transfusions differently, particularly regarding platelet and plasma use. These findings underscore the need for prospective studies to define optimal transfusion thresholds in this growing and vulnerable patient population, although the study's limited sample size and lack of diagnostic granularity may affect interpretation

Global transfusion practices in septic patients in the intensive care unit: insights from the InPUT ‐study sub‐analysis

Background: Transfusion practices among intensive care unit (ICU) patients with sepsis vary widely. While restrictive hemoglobin thresholds for red blood cell (RBC) transfusion are well studied, the indications and thresholds for platelet and plasma transfusions remain uncertain. Methods: We performed a sepsis‐specific sub‐analysis of the International Point Prevalence Study of Intensive Care Unit Transfusion Practices, a prospective, multicenter, observational study capturing all adult ICU admissions during four pre‐scheduled weeks between March 2019 and October 2022. Patients admitted with sepsis or septic shock, or who developed sepsis during their ICU stay, were included. We recorded demographics, daily laboratory values, and transfusion triggers. Primary endpoints were the proportions of patients receiving RBCs, platelets, or plasma; secondary endpoints were indications, pre‐transfusion thresholds, and blood loss. Results: Among 3643 screened patients, 799 (22%) fulfilled sepsis criteria; within this subgroup, 317 (40%) received at least one blood component. RBCs were transfused in 269 patients (34%), primarily to address anemia or hemodynamic instability, at a mean pre‐transfusion hemoglobin of 7.5 ± 1.4 g/dL, consistent with restrictive practice. Platelets were given to 78 patients (10%) for prophylaxis or active bleeding at a median count of 26 × 109 cells/L (interquartile range 16–51 × 109 cells/L). Plasma was administered to 108 patients (14%), half for bleeding control and half for non‐bleeding indications. Conclusions: This largest international snapshot of septic ICU transfusion practices confirms adherence to restrictive RBC thresholds but reveals substantial variability in platelet and plasma use. These findings underscore the need for targeted trials to refine transfusion guidelines in sepsis