Effect of different pressure-targeted modes of ventilation on transpulmonary pressure and inspiratory effort

Spontaneous breathing during mechanical ventilation improves gas exchange and might prevent ventilator- induced diaphragm dysfunction. In pressure-targeted modes, transpulmonary pressure (PL) is the sum of pres- sure generated by the ventilator and muscular pressure. When inspiratory effort increases, PL and tidal volume (VT) increase, potentially resulting in lung injury. This effect depends on the degree of inspiratory synchroniza- tion (i-sync); pressure-targeted modes can be classified into fully, partially, and non i-sync modes. A bench study [1] demonstrated that non-i-sync mode resulted in lower PL and VT than other modes, protecting the lungs from injury. We undertook to assess the effect of varying synchronization during pressure-targeted venti- lation in critically ill patients

The +276 G/T Single Nucleotide Polymorphism of the Adiponectin Gene Is Associated With Coronary Artery Disease in Type 2 Diabetic Patients

OBJECTIVE —Two single nucleotide polymorphisms (SNPs) at the adiponectin locus (+45T>G and +276G>T) have been associated with low circulating adiponectin levels, insulin resistance, and type 2 diabetes. We investigated whether these genetic markers are determinants of coronary artery disease (CAD) in type 2 diabetic patients. RESEARCH DESIGN AND METHODS —A total of 376 consecutive type 2 diabetic patients were studied: 142 case subjects with coronary stenosis >50% or previous myocardial infarction and 234 control subjects with no symptoms, no electrocardiogram (ECG) signs of myocardial ischemia, and a normal ECG stress test ( n = 189) and/or ( n = 45) with coronary stenosis ≤50%. RESULTS —No association with CAD was observed for the +45 SNP ( P = 0.48). By contrast, a significant association was observed for the +276 SNP, with T/T homozygotes having a lower risk of CAD than carriers of other genotypes (adjusted odds ratio [OR] 0.13 [95% CI 0.037–0.46], P = 0.002). A similarly protective effect of the +276 T/T genotype was observed in 110 case and 45 control subjects for whom the CAD status had been determined by angiography (0.04 [0.006–0.30], P = 0.002).  Serum adiponectin, although clearly related to several features of the proatherogenic/insulin-resistant phenotype, was not different between control subjects and CAD patients (26 ± 17 vs. 25 ± 13 μg/ml). CONCLUSIONS —In conclusion, the +276 G>T polymorphism is a determinant of CAD risk in type 2 diabetic patients. This marker may assist in the identification of diabetic individuals at especially high risk of CAD, so that preventive programs can be targeted at these subjects

Management of histoplasmosis by infectious disease physicians

BACKGROUND: The Infectious Diseases Society of America (IDSA) guidelines for the management of histoplasmosis were last revised 15 years ago. Since those guidelines were compiled, new antifungal treatment options have been developed. Furthermore, the ongoing development of immunomodulatory therapies has increased the population at increased risk to develop histoplasmosis. METHODS: An electronic survey about the management practices of histoplasmosis was distributed to the adult infectious disease (ID) physician members of the IDSA\u27s Emerging Infections Network. RESULTS: The survey response rate was 37% (551/1477). Only 46% (253/551) of respondents reported seeing patients with histoplasmosis. Regions considered endemic had 82% (158/193) of physicians report seeing patients with histoplasmosis compared to 27% (95/358) of physicians in regions not classically considered endemic ( CONCLUSIONS: Though there are increased reports of histoplasmosis diagnoses outside regions classically considered endemic, a majority of ID physicians reported not seeing patients with histoplasmosis. Most respondents reported adherence to IDSA guidelines recommending itraconazole in each clinical situation. New histoplasmosis guidelines need to reflect the growing need for updated general guidance, particularly for immunocompromised populations

The main concerns of European anaesthesiology postgraduate trainees: A European survey

This is the first study intended to identify the European anaesthesiology trainees' main concerns, to initiate a process of improvement of the training in anaesthesiology by the European Society of Anaesthesiology (ESA). The authors developed an electronic survey which addressed seven different concerns: autonomy transition, technical skills, exchange programs, residency costs, residency workload, employment prospects and educational contents/preparation for the European Diploma in Anaesthesiology and Intensive Care (EDAIC). The survey was disseminated by email to all anaesthesiology trainees registered in ESA and all European National Societies were asked to distribute the survey to their graduating trainees. 665 trainees initiated the survey with a completion rate of 54.6%. The trainees' main concerns were in descending order: educational contents, residency costs, employment prospects, residency workload, exchange programs, technical skills and autonomy transition. This report analyzes the three main concerns in more detail. 68% of respondents were unaware of the existence of the ESA e-learning platform. Other means to improve the preparation for the EDAIC such as a multiple-choice questions book should be developed. The main reason for not becoming an ESA Trainee member was the associated cost and 68% of respondents gave up activities or opportunities during their residency due to economic constraints; 56% of respondents considered emigrating for economic reasons and 28% elected Northern/Central Europe. The results of the present survey may provide additional background information for the development of specific improvements in strategies for training in anaesthesiology. (c) 2018 Elsevier Ltd. All rights reserved

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline

Purpose: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. Methods: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. Results: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). Conclusions: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial

IMPORTANCE: Immune dysregulation contributes to poorer outcomes in COVID-19. OBJECTIVE: To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021. INTERVENTIONS: Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day). MAIN OUTCOMES AND MEASURES: The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale. RESULTS: Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies. CONCLUSIONS AND RELEVANCE: Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04593940

Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

94noopenPurpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.openZanella A.; Florio G.; Antonelli M.; Bellani G.; Berselli A.; Bove T.; Cabrini L.; Carlesso E.; Castelli G.P.; Cecconi M.; Citerio G.; Coloretti I.; Corti D.; Dalla Corte F.; De Robertis E.; Foti G.; Fumagalli R.; Girardis M.; Giudici R.; Guiotto L.; Langer T.; Mirabella L.; Pasero D.; Protti A.; Ranieri M.V.; Rona R.; Scudeller L.; Severgnini P.; Spadaro S.; Stocchetti N.; Vigano M.; Pesenti A.; Grasselli G.; Aspesi M.; Baccanelli F.; Bassi F.; Bet A.; Biagioni E.; Biondo A.; Bonenti C.; Bottino N.; Brazzi L.; Buquicchio I.; Busani S.; Calini A.; Calligaro P.; Cantatore L.P.; Carelli S.; Carsetti A.; Cavallini S.; Cimicchi G.; Coppadoro A.; Dall'Ara L.; Di Gravio V.; Erba M.; Evasi G.; Facchini A.; Fanelli V.; Feliciotti G.; Fusarini C.F.; Ferraro G.; Gagliardi G.; Garberi R.; Gay H.; Giacche L.; Grieco D.; Guzzardella A.; Longhini F.; Manzan A.; Maraggia D.; Milani A.; Mischi A.; Montalto C.; Mormina S.; Noseda V.; Paleari C.; Pedeferri M.; Pezzi A.; Pizzilli G.; Pozzi M.; Properzi P.; Rauseo M.; Russotto V.; Saccarelli L.; Servillo G.; Spano S.; Tagliabue P.; Tonetti T.; Tullo L.; Vetrugno L.; Vivona L.; Volta C.A.; Zambelli V.; Zanoni A.Zanella, A.; Florio, G.; Antonelli, M.; Bellani, G.; Berselli, A.; Bove, T.; Cabrini, L.; Carlesso, E.; Castelli, G. P.; Cecconi, M.; Citerio, G.; Coloretti, I.; Corti, D.; Dalla Corte, F.; De Robertis, E.; Foti, G.; Fumagalli, R.; Girardis, M.; Giudici, R.; Guiotto, L.; Langer, T.; Mirabella, L.; Pasero, D.; Protti, A.; Ranieri, M. V.; Rona, R.; Scudeller, L.; Severgnini, P.; Spadaro, S.; Stocchetti, N.; Vigano, M.; Pesenti, A.; Grasselli, G.; Aspesi, M.; Baccanelli, F.; Bassi, F.; Bet, A.; Biagioni, E.; Biondo, A.; Bonenti, C.; Bottino, N.; Brazzi, L.; Buquicchio, I.; Busani, S.; Calini, A.; Calligaro, P.; Cantatore, L. P.; Carelli, S.; Carsetti, A.; Cavallini, S.; Cimicchi, G.; Coppadoro, A.; Dall'Ara, L.; Di Gravio, V.; Erba, M.; Evasi, G.; Facchini, A.; Fanelli, V.; Feliciotti, G.; Fusarini, C. F.; Ferraro, G.; Gagliardi, G.; Garberi, R.; Gay, H.; Giacche, L.; Grieco, D.; Guzzardella, A.; Longhini, F.; Manzan, A.; Maraggia, D.; Milani, A.; Mischi, A.; Montalto, C.; Mormina, S.; Noseda, V.; Paleari, C.; Pedeferri, M.; Pezzi, A.; Pizzilli, G.; Pozzi, M.; Properzi, P.; Rauseo, M.; Russotto, V.; Saccarelli, L.; Servillo, G.; Spano, S.; Tagliabue, P.; Tonetti, T.; Tullo, L.; Vetrugno, L.; Vivona, L.; Volta, C. A.; Zambelli, V.; Zanoni, A

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Semi-empirical relationships to assess the seismic performance of slopes from an updated version of the Italian seismic database

Funder: Dipartimento della Protezione Civile, Presidenza del Consiglio dei Ministri; doi: http://dx.doi.org/10.13039/100012783; Grant(s): ReLUIS research project - Working Pachage 16: Geotechnical Engineering - Task Group 2: Slope stabilityAbstractSeismic performance of slopes can be assessed through displacement-based procedures where earthquake-induced displacements are usually computed following Newmark-type calculations. These can be adopted to perform a parametric integration of earthquake records to evaluate permanent displacements for different slope characteristics and seismic input properties. Several semi-empirical relationships can be obtained for different purposes: obtaining site-specific displacement hazard curves following a fully-probabilistic approach, to assess the seismic risk associated with the slope; providing semi-empirical models within a deterministic framework, where the seismic-induced permanent displacement is compared with threshold values related to different levels of seismic performance; calibrating the seismic coefficient to be used in pseudo-static calculations, where a safety factor against limit conditions is computed. In this paper, semi-empirical relationships are obtained as a result of a parametric integration of an updated version of the Italian strong-motion database, that, in turn, is described and compared to older versions of the database and to well-known ground motion prediction equations. Permanent displacement is expressed as a function of either ground motion parameters, for a given yield seismic coefficient of the slope, or of both ground motion parameters and the seismic coefficient. The first are meant to be used as a tool to develop site-specific displacement hazard curves, while the last can be used to evaluate earthquake-induced slope displacements, as well as to calibrate the seismic coefficient to be used in a pseudo-static analysis. Influence of the vertical component of seismic motion on these semi-empirical relationships is also assessed.</jats:p