Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

[Background] Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia.[Methods] A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3).[Results] Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02).[Conclusions] Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.This study was funded by a research grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III [FIS PI15/00744], European Regional Development Fund (ERDF); CGV is a recipient of an INTENSIFICACIÓ Grant from the “Strategic plan for research and innovation in health-PERIS 2016-2020” and forms part of the Fungi CLINIC Research group (AGAUR-Project 2017SGR1432 of the Catalan Health Agency)

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03–6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04–4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12–0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08–4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Factors associated with the development of septic shock in patients with candidemia: A post hoc analysis from two prospective cohorts

Background: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. Methods: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). Results: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). Conclusions: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms

Association between preoperative evaluation with lung ultrasound and outcome in frail elderly patients undergoing orthopedic surgery for hip fractures: study protocol for an Italian multicenter observational prospective study (LUSHIP)

Hip fracture is one of the most common orthopedic causes of hospital admission in frail elderly patients. Hip fracture fixation in this class of patients is considered a high-risk procedure. Preoperative physical examination, plasma natriuretic peptide levels (BNP, Pro-BNP), and cardiovascular scoring systems (ASA-PS, RCRI, NSQIP-MICA) have all been demonstrated to underestimate the risk of postoperative complications. We designed a prospective multicenter observational study to assess whether preoperative lung ultrasound examination can predict better postoperative events thanks to the additional information they provide in the form of "indirect" and "direct" cardiac and pulmonary lung ultrasound signs

Dalbavancin in the treatment of acute bacterial skin and skin structure and other infections: a safety evaluation

Dalbavancin is a second-generation lipoglycopeptide approved since 2014 to treat acute bacterial skin and skin-structure infections (ABSSSI). Dalbavancin is characterized by Gram-positive activity and novel pharmacokinetic properties allowing prolonged terminal half-life andonce weekly dosing . A good safety profile was reported in clinical trials

Cerebral fat embolism after traumatic bone fractures: a structured literature review and analysis of published case reports

Background The incidence of cerebral fat embolism (CFE) ranges from 0.9-11%, with a mean mortality rate of around 10%. Although no univocal explanation has been identified for the resulting fat embolism syndrome (FES), two hypotheses are widely thought: the 'mechanical theory', and the 'chemical theory'. The present article provides a systematic review of published case reports of FES following a bone fracture. Methods We searched MEDLINE, Web of Science and Scopus to find any article related to FES. Inclusion criteria were: trauma patients; age >= 18 years; and the clinical diagnosis of CFE or FES. Studies were excluded if the bone fracture site was not specified. Results One hundred and seventy studies were included (268 cases). The male gender was most prominent (81.6% vs. 18.4%). The average age was 33 years (+/- 18). The mean age for males (29 +/- 14) was significantly lower than for females (51 +/- 26) (p < 0.001). The femur was the most common fracture site (71% of cases). PFO was found in 12% of all cases. Univariate and multivariate regression analyses showed the male gender to be a risk factor for FES: RR 1.87 and 1.41, respectively (95%CI 1.27-2.48, p < 0.001; 95%CI 0.48-2.34, p < 0.001). Conclusions FES is most frequent in young men in the third decades of life following multiple leg fractures. FES may be more frequent after a burst fracture. The presence of PFO may be responsible for the acute presentation of cerebral embolisms, whereas FES is mostly delayed by 48-72 h

Colonisation with Extended-Spectrum Cephalosporin-Resistant Enterobacterales and Infection Risk in Surgical Patients: A Systematic Review and Meta-analysis

Introduction: Limited evidence has been reported for surgical site infections (SSIs) in patients undergoing surgery who are carriers of extended-spectrum cephalosporin-resistant Enterobacterales (ESCR-E). A systematic review and meta-analysis were conducted to evaluate the risk of postoperative infections in adult inpatients colonised with ESCR-E before surgery. Methods: The Medline, Embase and Cochrane databases were searched between January 2011 and April 2022, following PRISMA indications. Random effects meta-analysis was used to quantify the association between ESCR-E colonisation and infection. Results: Among the 467 articles reviewed, 9 observational studies encompassing 7219 adult patients undergoing surgery were included. The ESCR-E colonisation rate was 13.7% (95% CI 7.7-19.7). The most commonly reported surgeries included abdominal surgery (44%) and liver transplantation (LT; 33%). The SSI rate was 23.2% (95% CI 13.2-33.1). Pooled incidence risk was 0.36 (95% CI 0.22-0.50) vs 0.13 (95% CI 0.02-0.24) for any postoperative infection and 0.28 (95% CI 0.18-0.38) vs 0.17 (95% CI 0.07-0.26) for SSIs in ESCR-E carriers vs noncarriers, respectively. In ESCR-E carriers, the ESCR-E infection ratio was 7 times higher than noncarriers. Postoperative infection risk was higher in carriers versus noncarriers following LT. Sources of detected heterogeneity between studies included ESCR-E colonisation and the geographic region of origin. Conclusions: Patients colonised with ESCR-E before surgery had increased incidence rates of post-surgical infections and SSIs compared to noncarriers. Our results suggest considering the implementation of pre-surgical screening for detecting ESCR-E colonisation status according to the type of surgery and the local epidemiology

A Multiparametric Method Improves the Serological Characterization of Inflammatory Bowel Diseases: Preliminary Results from a Multicenter Eastern Europe Study

The serological support for early diagnosis and differential diagnosis of inflammatory bowel diseases (IBDs) is actually very limited. In this study, we evaluated the performance of a promising multiparametric method including either well-established and newly developed biomarkers. We conducted a multicenter cross-sectional study at the Gastroenterology Units of Udine (Italy), Rijeka (Croatia) and Belgrade (Serbia). Sera was collected from IBD patients, and autoantibody profiles were determined using a mosaic cell and tissue-based indirect immunofluorescence (IIF) method simultaneously investigating anti-saccharomyces cerevisiae antibodies (ASCAs), anti-atypical perinuclear neutrophilic antibodies (P-ANCAs), anti-pancreatic antigens antibodies (PABs) and anti-goblet cells antibodies (GAB). The study finally enrolled 156 patients with IBD: 100 affected by Crohn’s disease (CD) and 56 by ulcerative colitis (UC). Twenty age-sex matched blood donors (BDs) were included as controls. PAB (anti-CUZD1 and/or anti-GP2 antibodies) were present in 24 CD patients versus none of the UC patients or BDs (24% sensitivity, 100% specificity). As regards CD patients, combined positivity of PAB and ASCA (sensitivity 84%, specificity 71.4%) performed better than ASCA alone. Colon involvement (87.5% vs. 60.5%; p = 0.014), deep mucosal lesions (58.3% vs. 25.0%; p = 0.002) and need for biologic therapies (79.2% vs. 46.1%; p = 0.005) were significantly more prevalent in PAB-positive than in PAB-negative CD patients. Multivariate analysis identified PAB positivity (OR = 3.67; 95%CI = 1.29–10.46) and anti-CUZD1 in particular (OR = 3.54; 95%CI = 1.08–11.63) as significant risk factors for deep mucosal lesion development in CD. A multiparametric diagnostic approach appears very useful to better characterize IBD patients. PABs, whether isolated or combined with other autoantibodies, may support differential diagnosis but above all facilitate the selection of CD patients at risk for more severe disease

VENTILATORY ASSOCIATED BAROTRAUMA IN COVID-19 PATIENTS: A MULTICENTER OBSERVATIONAL CASE CONTROL STUDY (COVI-MIX-STUDY)

Background The risk of barotrauma associated with different types of ventilatory support is unclear in COVID- 19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. Methods This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. Results We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82- 10.03, p<0.001). ConclusionsC-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. Trial registration: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021). Keywords: COVID-19, acute respiratory failure, barotrauma, pneumothorax, High Flow Nasal Cannula, Invasive Mechanical Ventilation

Clinical phenotypes and quality of life to define post-COVID-19 syndrome: a cluster analysis of the multinational, prospective ORCHESTRA cohortResearch in context

Summary: Background: Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs. Methods: This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677. Findings: Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively). Interpretation: Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials. Funding: The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch &amp; ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424