A Fatal Case of Nosocomial Legionnaires' Disease: Implications From an Extensive Environmental Investigation and Isolation of the Bacterium From Blood Culture

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Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study

BACKGROUND: One key element of lung-protective ventilation is the use of a low tidal volume (VT). A sex difference in use of low tidal volume ventilation (LTVV) has been described in critically ill ICU patients.OBJECTIVES: The aim of this study was to determine whether a sex difference in use of LTVV also exists in operating room patients, and if present what factors drive this difference.DESIGN, PATIENTS AND SETTING: This is a posthoc analysis of LAS VEGAS, a 1-week worldwide observational study in adults requiring intra-operative ventilation during general anaesthesia for surgery in 146 hospitals in 29 countries.MAIN OUTCOME MEASURES: Women and men were compared with respect to use of LTVV, defined as VT of 8 ml kg-1 or less predicted bodyweight (PBW). A VT was deemed 'default' if the set VT was a round number. A mediation analysis assessed which factors may explain the sex difference in use of LTVV during intra-operative ventilation.RESULTS: This analysis includes 9864 patients, of whom 5425 (55%) were women. A default VT was often set, both in women and men; mode VT was 500 ml. Median [IQR] VT was higher in women than in men (8.6 [7.7 to 9.6] vs. 7.6 [6.8 to 8.4] ml kg-1 PBW, P < 0.001). Compared with men, women were twice as likely not to receive LTVV [68.8 vs. 36.0%; relative risk ratio 2.1 (95% CI 1.9 to 2.1), P < 0.001]. In the mediation analysis, patients' height and actual body weight (ABW) explained 81 and 18% of the sex difference in use of LTVV, respectively; it was not explained by the use of a default VT.CONCLUSION: In this worldwide cohort of patients receiving intra-operative ventilation during general anaesthesia for surgery, women received a higher VT than men during intra-operative ventilation. The risk for a female not to receive LTVV during surgery was double that of males. Height and ABW were the two mediators of the sex difference in use of LTVV.TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov, NCT01601223

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Arterial thrombo-embolic events in cardiac amyloidosis: a look beyond atrial fibrillation

Background Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort. Methods and results Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from 5 Italian referral centres were retrospectively evaluated and followed-up for a median time of 19 months. Thirty-one patients (7.6%) suffered from an AE, of whom 10 (32.2%) were in sinus rhythm and had no history of AF. There were no significant differences in terms of age, gender and type of CA between patients with or without AEs. Fourteen (7.6%) of 185 patients on anticoagulation had an AE despite therapy. Anticoagulation therapy did not appear to fully protect from the risk of events (HR 1.23, 95%CI 0.52-2.92,p = .64). The only predictor of AEs, in particular among CA patients in sinus rhythm, was a CHA2DS2-VASC score >= 3 (HR 2.84, 95%CI 1.02-7.92,p = .05 in overall population; HR 10.13, 95%CI 1.12-91.19,p = .04 in patients in sinus rhythm). Conclusions In our large, multicentric, real-world cohort, prevalence and incidence rate of AEs was high. A consistent proportion of events occurred despite anticoagulation therapy or in patients in sinus rhythm. A higher CHA2DS2-VASc score might identify patients at risk of AEs also among those in sinus rhythm

Clinical Features and Mortality of Nosocomial Candidemia in Very Old Patients: A Multicentre Italian Study

Introduction: Being elderly is a well-known risk factor for candidemia, but few data are available on the prognostic impact of candidemia in the very old (VO) subjects, as defined as people aged 6575 years. Objective: The aim of this study was to assess risk factors for nosocomial candidemia in two groups of candidemia patients, consisting of VO patients ( 6575 years) and adult and old (AO) patients (18\u201374 years). In addition, risk factors for death (30-day mortality) were analysed separately in the two groups. Methods: We included all consecutive candidemia episodes from January 2011 to December 2013 occurring in six referral hospitals in north-eastern Italy. Results: A total of 683 nosocomial candidemia episodes occurred. Of those, 293 (42.9%) episodes were in VO and 390 (57.1%) in AO patients. Hospitalization in medical wards, chronic renal failure, urinary catheter, and peripheral parenteral nutrition (PPN) were more common in VO than in AO patients. In the former patient group, adequate antifungal therapy (73.2%) and central venous catheter (CVC) removal (67.6%) occurred less frequently than in AO patients (82.5 and 80%, p < 0.002 and p < 0.004, respectively). Thirty-day mortality was higher in VO compared to AO patients (47.8 vs. 23.6%, p < 0.0001). In AO patients, independent risk factors for death were age (OR 1.04, 95% CI 1.00\u20131.09, p = 0.038), recent history of chemotherapy (OR 22.01, 95% CI 3.12\u2013155.20, p = 0.002), and severity of sepsis (OR 40.68, 95% CI 7.42\u2013223.10, p < 0.001); CVC removal was associated with higher probability of survival (OR 0.10, 95% CI 0.03\u20130.33, p < 0.001). In VO patients, independent risk factors for death were PPN (OR 3.5, 95% CI 1.17\u201310.47, p = 0.025) and hospitalization in medical wards (OR 2.58, 95% CI 1.02\u20136.53, p = 0.046), while CVC removal was associated with improved survival (OR 0.40, 95% CI 0.16\u20131.00, p = 0.050). Conclusion: Thirty-day mortality was high among VO patients and was associated with inadequate management of candidemia, especially in medical wards

Bedside diagnostic laparoscopy for critically ill patients in the Intensive Care Unit: Retrospective study and review of literature

Background: Bedside diagnostic laparoscopy could be helpful in extremely critically ill patients. The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients and to compare its accuracy and outcomes with the ones of laparotomy. Patients and Methods: A retrospective review was conducted on the medical records of patients admitted to the Intensive Care Unit (ICU) of Careggi University Hospital and submitted to bedside diagnostic laparoscopy between January 2006 and May 2017. This group of patients was compared with a group of patients that were admitted to the ICU and submitted directly to explorative laparotomy for suspected intra-abdominal pathologies. Results: One hundred and twenty-nine patients (M/F = 81/48, mean age = 71.64 years) underwent bedside diagnostic laparoscopy in ICU. 154 patients instead were submitted directly to explorative laparotomy in operatory room (mean age 75.70 years, M/F = 94/60). Among the 129 patients submitted to bedside laparoscopy, 53.49% were positive for intra-abdominal pathologies whereas 46.51% were negative, while among the 154 patients submitted directly to laparotomy, 76.62% were positive for intra-abdominal pathologies whereas 23.38% were negative. In 55.03% of all patients submitted to bedside laparoscopy, a non-therapeutic laparotomy was avoided, while the 33.76% of patients submitted directly to laparotomy had a non-therapeutic laparotomy that could be avoidable. Conclusions: Our results pinpoint the advantages of performing bedside diagnostic laparoscopy in the ICU setting, which can be considered an option every time there is the suspicion of an intra-abdominal pathology