Background and purpose: Mounting evidence supports an association between Guillain− Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach.Methods: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients.Results: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I 2 = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27,

Invasive candidiasis is a life-threatening infection in patients with haematological malignancies. The objective of our study was to determine the incidence, microbiological characteristics and clinical outcome of candidaemia among hospitalized adult patients with haematological malignancies. This is a population-based, prospective, multicentre study of patients ≥ 18 years admitted to haematology and/or haematopoietic stem cell transplantation units of nine tertiary care Greek hospitals from January 2009 through to February 2012. Within this cohort, we conducted a nested case-control study to determine the risk factors for candidaemia. Stepwise logistic regression was used to identify independent predictors of 28-day mortality. Candidaemia was detected in 40 of 27,864 patients with haematological malignancies vs. 967 of 1,158,018 non-haematology patients for an incidence of 1.4 cases/1000 admissions vs. 0.83/1000 respectively (p <0.001). Candidaemia was caused predominantly (35/40, 87.5%) by non-Candida albicans species, particularly Candida parapsilosis (20/40, 50%). In vitro resistance to at least one antifungal agent was observed in 27% of Candida isolates. Twenty-one patients (53%) developed breakthrough candidaemia while receiving antifungal agents. Central venous catheters, hypogammaglobulinaemia and a high APACHE II score were independent risk factors for the development of candidaemia. Crude mortality at day 28 was greater in those with candidaemia than in control cases (18/40 (45%) vs. 9/80 (11%); p <0.0001). In conclusion, despite antifungal prophylaxis, candidaemia is a relatively frequent infection associated with high mortality caused by non-C. albicans spp., especially C. parapsilosis. Central venous catheters and hypogammaglobulinaemia are independent risk factors for candidaemia that provide potential targets for improving the outcome.

R Re es sp pi ir ra at to or ry y m mu us sc cl le es s a an nd d w we ea an ni in ng g f fa ai il lu ur re e ABSTRACT: Weaning failure is, unfortunately, a rather common phenomenon for mechanically-ventilated patients (especially those with chronic obstructive pulmonary disease (COPD)), and the respiratory muscles play a pivotal role in its development.Weaning fails whenever an imbalance exists between the ventilatory needs and the neurocardiorespiratory capacity. This can happen if there is an increase in the energy demands of the respiratory muscles, a decrease in the energy available, a decrease in neuromuscular competence, or if the respiratory muscles pose an impediment to the heart and blood flow.The imbalance created will lead to weaning failure through the development of respiratory muscle fatigue, hypercapnia, dyspnoea, anxiety and organ dysfunction.

We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development.45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (DPCT, DCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables.No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were DPCT 7-1 (OR 7.23, 95% CI 0.008-0.468) and DCRP 7-4 (OR 4.59, 95% CI 0.013-0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330-5.715).Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.

study, we evaluated the differential influence of chronic treadmill training (30 m/min, 15% incline, 1 h/day, 5 days/wk) on nitric oxide (NO) production and NO synthase (NOS) isoform expression as well as 3-nitrotyrosine formation (footprint of peroxynitrite) both in limb (gastrocnemius) and ventilatory (diaphragm) muscles. A group of exercise-trained rats and a control group (no training) were examined after a 4-wk experimental period. Exercise training elicited an approximate fourfold rise in gastrocnemius NOS activity and augmented protein expression of the endothelial (eNOS) and neuronal (nNOS) isoforms of NOS to ϳ480% and 240%, respectively. Qualitatively similar but quantitatively smaller elevations in NOS activity and eNOS and nNOS expression were observed in the diaphragm. No detectable inducible NOS (iNOS) protein expression was found in any of the muscle samples.

Resistive breathing is an "immune challenge" for the body, initiating an inflammatory response consisting of an elevation of plasma cytokines, and the recruitment and activation of lymphocyte subpopulations. These cytokines do not originate from monocytes, but are, instead, produced within the diaphragm, secondary to the increased muscle activation.Oxidative stress is a major stimulus for the cytokine induction, secondary to resistive breathing. The production of cytokines within the diaphragm may be mediating the diaphragm muscle fibre injury that occurs with strenuous contractions, or contributing towards the expected repair process. These cytokines may also compromise diaphragmatic contractility or contribute towards the development of muscle cachexia. They may also have systemic effects, mobilising glucose from the liver and free fatty acid from the adipose tissue to the strenuously working respiratory muscles. At the same time, they stimulate the hypothalamic-pituitary-adrenal axis, leading to production of adrenocorticotropin and b-endorphins.The adrenocorticotropin response may represent an attempt of the organism to reduce the injury occurring in the respiratory muscles via the production of glucocorticoids and the induction of the acute phase-response proteins. The b-endorphin response would decrease the activation of the respiratory muscles and change the pattern of breathing, which becomes more rapid and shallow, possibly in an attempt to reduce and/or prevent further injury to the respiratory muscles.

Background and Objectives:There is accumulating evidence supporting an association between the “thrombosis and thrombocytopenia syndrome” (TTS) and adenovirus vector-based vaccines against SARS-CoV-2. Yet, TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes.Methods:We performed a systematic review and meta-analysis of clinical trials, cohorts, case series and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with post-vaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal.Results:Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were further included in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95%CI:36-66%; I2=61%). TTS was independently associated with a higher likelihood of CVST, when compared to non-TTS patients with thrombotic events after vaccination (OR:13.8; 95%CI:2.0-97.3; I2=78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95%CI:21-36%) and 38% (95%CI:27-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval:10 days; 95%CI:8-12) and affected predominantly women (69%, 95%CI:60-77%), under the age of 45, even in the absence of pro-thrombotic risk factors.Discussion:Approximately one half of TTS cases present with CVST, while almost one third of TTS patients do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination.Registration:The pre-specified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).

We studied 31 consecutive mechanically ventilated patients with acute respiratory failure in two stages: (1) During spontaneous breathing through the respirator, switching from full mechanical assistance to continuous positive airway pressure mode with 0 cm H2O pressure. We measured maximum inspiratory pressure and continuously monitored the pattern of breathing. After 8 to 25 min, none of the patients were able to sustain spontaneous breathing and mechanical ventilation was required to resume. (2) Subsequently, during mechanical ventilation, by manipulating the variables of the ventilator we simulated the pattern of spontaneous breathing the patients had just before the re-institution of mechanical ventilation. We assessed the respiratory mechanics by the constant flow end-inspiratory and end-expiratory occlusion method. Intrinsic positive end-expiratory pressure was present in 29 patients. The ratio of the mean inspiratory pressure per breath over the maximum inspiratory pressure (Pi/pimax), as well as Ppeak/pimax, had excessively high mean values, equal to 0.42 +/- 0.11 and 0.56 +/- 0.10, respectively. Pressure-time index was 0.14 +/- 0.04. When we plotted the Pi/Pimax and Ppeak/Pimax against the dynamic increase in FRC, we found that the Pi/Pimax of 13 patients (42%) and the Ppeak/Pimax of 25 of 31 patients (81%) were placed above a hypothetical critical line, representing the critical inspiratory pressures above which fatigue may occur. In addition, almost all patients were gathered around the critical line. We conclude that during discontinuation from mechanical ventilation (MV) almost all patients breathe against a high inspiratory load and their inspiratory muscles perform work that may lead to fatigue.