BACKGROUND: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis.
METHODS: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019.
RESULTS: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality).
CONCLUSIONS: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE.

Honeybee bites are a common public health hazard, the incidence of which is gradually increasing. A bee sting incident involving more than fifty stings is categorized as massive envenomation. The clinical manifestations of honey bee stings can range from localized symptoms to severe allergic and systemic reactions.This case study presents a 60-year-old male who experienced multi-organ failure following a severe bee sting incident. According to our research, this is the first documented instance in Somalia of multi-organ failure resulting from a sting by a giant honey bee. The case highlights the potential severity of bee stings, which, while often considered minor, can lead to serious medical complications. Interestingly, despite the patient suffering numerous stings and receiving a substantial amount of venom, an immediate anaphylactic reaction did not occur. Instead, a delayed severe response leading to multi-organ failure emerged within 48 hours of the incident.

Facial appearance, whether consciously or subconsciously assessed, may affect clinical assessment and treatment strategies in the Intensive Care Unit (ICU). Nevertheless, the association between objective clinical measurement of facial appearance and multi-organ failure is currently unknown. The objective of this study was to examine whether facial appearance at admission is associated with longitudinal evaluation of multi-organ failure.
This was a sub-study of the Simple Intensive Care Studies-II, a prospective observational cohort study. All adult patients acutely admitted to the ICU between March 26, 2019, and July 10, 2019, were included. Facial appearance was assessed within three hours of ICU admission using predefined pictograms. The SOFA score was serially measured each day for the first seven days after ICU admission. The association between the extent of eye-opening and facial skin colour with longitudinal Sequential Organ Failure Assessment (SOFA) scores was investigated using generalized estimation equations.
SOFA scores were measured in 228 patients. Facial appearance scored by the extent of eye-opening was associated with a higher SOFA score at admission and follow-up (unadjusted 0.7 points per step (95%CI 0.5 to 0.9)). There was no association between facial skin colour and a worse SOFA score over time. However, patients with half-open or closed eyes along with flushed skin had a lower SOFA score than patients with a pale or normal facial skin colour (P-interaction < 0.1).
The scoring of patients\' facial cues, primarily the extent of eye-opening and facial colour, provided valuable insights into the disease state and progression of the disease of critically ill patients. The utilization of advanced monitoring techniques that incorporate facial appearance holds promise for enhancing future intensive care support.

Organ transplantation is the primary therapy for organ failure caused by telomere biology disorder (TBD). We describe the first documented case of simultaneous liver and kidney transplantation (SLKTx) for TBD, although the diagnosis of TBD was reached only three months following SLKTx. The patient was born prematurely, displayed growth retardation, and developed chronic kidney and liver diseases. His pre-SLKTx autoimmune, metabolic, and viral assessments were negative, and persistent pancytopenia (bone marrow cellularity 70-80%) was attributed to renal disease-associated bone marrow changes. Following SLKTx, he was discharged with stable graft function on tacrolimus and prednisolone. Although mycophenolate mofetil was discontinued on the second postoperative day, his pancytopenia persisted. Despite extensive evaluations, including drug, immune, nutritional, and viral assessments, all results were negative. A bone marrow biopsy conducted three months post-transplant revealed significant hypocellularity (40-50%). Whole genome sequencing revealed a likely pathogenic variant of the TINF2 gene. The patient was subsequently treated with danazol. At the nine-month follow-up post-SLKTx, he exhibited stable graft function and improved cell counts while maintaining triple-drug immunosuppression. Given the lack of uniform diagnostic criteria for TBD, healthcare providers must be vigilant with patients presenting with multi-organ failure and persistent cytopenias. Effective pre-transplant screening for TBD can lead to timely diagnoses, better management, and improved post-transplant outcomes.

Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein.
We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses.
Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time.
The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients.
gov Identifier: NCT03160547 (2017-05-17).

BACKGROUND: Critically ill patients with cirrhosis and ascites are at high risk for intra-abdominal hypertension (IAH) which increases mortality. Clinical guidelines recommend maintaining intra-abdominal pressure (IAP) below 16 mmHg; nonetheless, more than three quarters of critically ill patients with cirrhosis develop IAH during their first week of ICU stay. Standard-of-care intermittent large-volume paracentesis (LVP) relieves abdominal wall tension, reduces IAP, optimizes abdominal perfusion pressure, and is associated with short-term improvement in renal and pulmonary dysfunction. However, there is no evidence of the superiority of different paracentesis strategies in the prevention and treatment of IAH in critically ill patients with cirrhosis. This trial aims to compare the outcomes of continuous passive paracentesis versus LVP in the prevention and treatment of IAH in patients with cirrhosis and ascites.
METHODS: An investigator-initiated, open label, randomized controlled trial, set in a general ICU specialized in liver disease, was initiated in August 2022, with an expected duration of 36 months. Seventy patients with cirrhosis and ascites will be randomly assigned, in a 1:1 ratio, to receive one of two methods of therapeutic paracentesis. A stratified randomization method, with maximum creatinine and IAP values as strata, will homogenize patient baseline characteristics before trial group allocation, within 24 h of admission. In the control group, LVP will be performed intermittently according to clinical practice, with a maximum duration of 8 h, while, in the intervention group, continuous passive paracentesis will drain ascitic fluid for up to 7 days. The primary endpoint is serum creatinine concentration, and secondary endpoints include IAP, measured creatinine clearance, daily urine output, stage 3 acute kidney injury and multiorgan dysfunction assessed at day 7 after enrollment, as well as 28-day mortality rate and renal replacement therapy-free days, and length-of-stay. Prespecified values will be used in case of renal replacement therapy or, beforehand ICU discharge, liver transplant and death. Safety analysis will include paracentesis-related complication rate and harm. Data will be analyzed with an intention-to-treat approach.
CONCLUSIONS: This is the first trial to compare the impact of different therapeutic paracentesis strategies on organ dysfunction and outcomes in the prevention and treatment of IAH in critically ill patients with cirrhosis and ascites.
BACKGROUND: ClinicalTrials.gov NCT04322201 . Registered on 20 December 2019.

UNASSIGNED: Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, there is no curative intent therapy able to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating NET-forming neutrophils [NET + Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets.
UNASSIGNED: We conducted a prospective observational study of circulating levels of CD11b + [NET + N] immunotyped for dual endothelin-1/signal peptide receptor (DEspR ±) expression by quantitative immunofluorescence-cytology and causal mediation analysis. In 36 consented adults hospitalized with mod-severe COVID-19, May to September 2020, we measured acute multi-organ failure via SOFA-scores and respiratory failure via SaO2/FiO2 (SF)-ratio at time points t1 (average 5.5 days from ICU/hospital admission) and t2 (the day before ICU-discharge or death), and ICU-free days at day28 (ICUFD). Circulating absolute neutrophil counts (ANC) and [NET + N] subset-specific counts were measured at t1. Spearman correlation and causal mediation analyses were conducted.
UNASSIGNED: Spearman correlation analyses showed correlations of t1-SOFA with t2-SOFA (rho r S  = 0.80) and ICUFD (r S  = -0.76); circulating DEspR + [NET + Ns] with t1-SOFA (r S  = 0.71), t2-SOFA (r S  = 0.62), and ICUFD (r S  = -0.63), and ANC with t1-SOFA (r S  = 0.71), and t2-SOFA (r S  = 0.61).Causal mediation analysis identified DEspR + [NET + Ns] as mediator of 44.1% [95% CI:16.5,110.6] of the causal path between t1-SOFA (exposure) and t2-SOFA (outcome), with 46.9% [15.8,124.6] eliminated when DEspR + [NET + Ns] were theoretically reduced to zero. Concordantly, DEspR + [NET + Ns] mediated 47.1% [22.0,72.3%] of the t1-SOFA to ICUFD causal path, with 51.1% [22.8,80.4%] eliminated if DEspR + [NET + Ns] were reduced to zero. In patients with t1-SOFA > 1, the indirect effect of a hypothetical treatment eliminating DEspR + [NET + Ns] projected a reduction of t2-SOFA by 0.98 [0.29,2.06] points and ICUFD by 3.0 [0.85,7.09] days. In contrast, there was no significant mediation of SF-ratio through DEspR + [NET + Ns], and no significant mediation of SOFA-score through ANC.
UNASSIGNED: Despite equivalent correlations, DEspR + [NET + Ns], but not ANC, mediated progression of multi-organ failure in acute COVID-19, and its hypothetical reduction is projected to improve ICUFD. These translational findings warrant further studies of DEspR + [NET + Ns] as potential patient-stratifier and actionable therapeutic target for multi-organ failure in COVID-19.
UNASSIGNED: The online version contains supplementary material available at 10.1186/s41231-023-00143-x.

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA, \"ecstasy\") abuse is frequent, and overdosing might cause severe and eventually lethal multi-organ failure. To date, there is no causal therapy of MDMA intoxication and removal of MDMA from the circulation might be a reasonable measure to prevent adverse courses after overdosing. We present here first-in-man experience and in vitro data supporting a potential role of an adsorber device in severe MDMA overdosing.
RESULTS: We applied a CytoSorb adsorber device in a 21-year-old male presenting with severe MDMA intoxication and multi-organ failure, including neurological impairment, hyperpyrexia, rhabdomyolysis, oliguric renal failure, liver failure, and coagulopathy with disseminated gastrointestinal and intramuscular bleeding. Use of the adsorber device was associated with a decline in MDMA concentrations in serum from 540 to 140 ng/ml within the first 24 h, a decrease of interleukin 6 and myoglobin levels, and subsequent clinical improvement. The patient was discharged from hospital after restoration of organ function and full neurological recovery. Effective elimination of MDMA by the adsorber device could be confirmed in vitro, when the device lowered MDMA concentrations to non-detectable levels.
CONCLUSIONS: We report here first-in-man experience and in vitro data showing the capacity of a CytoSorb adsorber device for MDMA removal. Early integration of CytoSorb use may enhance the management of severe MDMA intoxication, though we cannot prove whether clinical improvement was directly related to elimination of MDMA or beneficial effects on rhabdomyolysis, hyperinflammation, or liver failure. Our findings encourage further investigation of the CytoSorb adsorber device in a prospective study and to evaluate its use for other intoxications.

OBJECTIVE: An evaluation is made of the hospital mortality predicting capacity of the main predictive scoring systems.
METHODS: A 2-year retrospective cohort study was carried out.
METHODS: A third level ICU with surgical and medical patients.
METHODS: All patients with multiorgan failure during the first day in the ICU.
METHODS: APACHE II and IV, SAPS II and III, MPM II and hospital mortality.
RESULTS: A total of 568 patients were included. Mortality rate: 39.8% (226 patients). Discrimination (area under the ROC curve; 95% CI): APACHE IV (0.805; 0.751-0.858), SAPS II (0.755; 0.697-0.814), MPM II (0.748; 0.688-0.809), SAPS III (0.737; 0.675-0.799) and APACHE II (0.699; 0.633-0.765). MPM II showed the best calibration, followed by SAPS III. APACHE II, SAPS II and APACHE IV showed very poor calibration. Standard mortality ratio (95% CI): APACHE IV 1.9 (1.78-2.02); APACHE II 1.1 (1.07-1.13); SAPS III 1.1 (1.06-1.14); SAPS II 1.03 (1.01-1.05); MPM 0.9 (0.86-0.94).
CONCLUSIONS: APACHE IV showed the best discrimination, with poor calibration. MPM II showed good discrimination and the best calibration. SAPS II, in turn, showed the second best discrimination, with poor calibration. The APACHE II calibration and discrimination values currently disadvise its use. SAPS III showed good calibration with modest discrimination. Future studies at regional or national level and in certain critically ill populations are needed.

OBJECTIVE: To assess whether the administration of symbiotic preparations in patients with multi-organ failure (MOF) diminishes the evolution of the failure, the inflammatory response generated, the colonization pattern and the Intensive Care Unit (ICU) infectious illness.
METHODS: Randomized and controlled trial. All patients with MOF were included. Neutropenia and acute pancreatitis patients were excluded. A symbiotic (Simbiotic Drink) was administered via enteral feeding during the first 7 days. Variables of interest were: Sequential Organ Failure Assessment (SOFA) score evolution, systemic concentrations of lactate, fibrinogen and D-dimer; skin and mucosa colonization and infectious disease register.
RESULTS: Eighty-nine patients were included; 46 in the symbiotic group (SG) and 43 in the control group (CG). There were 68.5% males, with a median age of 69 years. There were no significant differences in the patients\' fundamental characteristics (medical history, age, reason for admission, severity scores), nor in the length of ICU stay or in mortality. Comparing the SG with the CG, there were lower lactate levels on the second day, more fibrinogen levels on the days 5 and 7, and lower D-dimer levels on the day 7. Eight hundred and ninety-five cultures were performed for colonization assessment, with isolation of 528 microorganisms. No differences in microbiological resistance were found; there were more colonization in the SG by Candida in mucous membranes after the third day; this situation resolved after stopping symbiotic administration. Twenty-two patients suffered an infectious disease in ICU, 14 in SG (42.4%) and 19 in CG (57.6%). Although no differences were found in the microbiological pattern, there was a predominance of Candida spp. over other microorganisms (4 vs. 0 cases).
CONCLUSIONS: The symbiotic preparation Simbiotic Drink, administered in MOF, results in differences to improve the early lactate levels and late fibrinogen/D-dimer levels as well as mucosa colonization by Candida. There were no differences in the ICU evolution.