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Purpose 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. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06495-y.

Background Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. Methods Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. Results Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p 2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). Conclusions During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. Trial registration: clinicaltrials.gov number: NCT04388670

BACKGROUND: The aim of this study was to evaluate whether measurement of diaphragm thickness (DT) by ultrasonography may be a clinically useful noninvasive method for identifying patients at risk of adverse outcomes defined as need of invasive mechanical ventilation or death. METHODS: We prospectively enrolled 77 patients with laboratory-confirmed COVID-19 infection admitted to our intermediate care unit in Pisa between March 5 and March 30, 2020, with follow-up until hospital discharge or death. Logistic regression was used identify variables potentially associated with adverse outcomes and those P

Background and aim: There is a need to determine which clinical variables predict the severity of COVID-19. We analyzed a series of critically ill COVID-19 patients to see if any of our dataset’s clinical variables were associated with patient outcomes. Methods: We retrospectively analyzed the data of COVID-19 patients admitted to the ICU of the Hospital in Pordenone from March 11, 2020, to April 17, 2020. Patients’ characteristics of survivors and deceased groups were compared. The variables with a different distribution between the two groups were implemented in a generalized linear regression model (LM) and in an Artificial Neural Network (NN) model to verify the “robustness” of the association with mortality. Results: In the considered period, we reviewed the data of 22 consecutive patients: 8 died. The causes of death were a severe respiratory failure (3), multi-organ failure (1), septic shock (1), pulmonary thromboembolism (2), severe hemorrhage (1). Lymphocyte and the platelet count were significantly lower in the group of deceased patients (p-value 0.043 and 0.020, respectively; cut-off values: 660/mm3; 280,000/mm3, respectively). Prothrombin time showed a statistically significant trend (p-value= 0.065; cut-off point: 16.8/sec). The LM model (AIC= 19.032), compared to the NN model (Mean Absolute Error, MAE = 0.02), was substantially alike (MSE 0.159 vs. 0.136). Conclusions: In the context of critically ill COVID-19 patients admitted to ICU, lymphocytopenia, thrombocytopenia, and lengthening of prothrombin time were strictly correlated with higher mortality. Additional clinical data are needed to be able to validate this prognostic score. (www.actabiomedica.it)

Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF.We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases.Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison.None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.

Background 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. Methods LUSHIP is an Italian multicenter prospective observational study. Patients will be recruited on a nation-wide scale in the 12 participating centers. Patients aged > 65 years undergoing spinal anesthesia for hip fracture fixation will be enrolled. A lung ultrasound score (LUS) will be generated based on the examination of six areas of each lung and ascribing to each area one of the four recognized aeration patterns—each of which is assigned a subscore of 0, 1, 2, or 3. Thus, the total score will have the potential to range from a minimum of 0 to a maximum of 36. The association between 30-day postoperative complications of cardiac and/or pulmonary origin and the overall mortality will be studied. Considering the fact that cardiac complications in patients undergoing hip surgery occur in approx. 30% of cases, to achieve 80% statistical power, we will need a sample size of 877 patients considering a relative risk of 1.5. Conclusions Lung ultrasound (LU), as a tool within the anesthesiologist’s armamentarium, is becoming increasingly widespread, and its use in the preoperative setting is also starting to become more common. Should the study demonstrate the ability of LU to predict postoperative cardiac and pulmonary complications in hip fracture patients, a randomized clinical trial will be designed with the scope of improving patient outcome. Trial registration ClinicalTrials.gov, NCT04074876. Registered on August 30, 2019.

Introduction. Influenza represents a matter of serious concern for clinicians, both for outpatient and in hospital setting. The 2017-18 epidemic represented the highest in terms of severity since 2003-04 worldwide. Overall, in Italy 764 cases was classified as “severe form”, with 173 influenza-attributed deaths . The majority of the fatal cases were recorded in the elderly and in patients with multiple comorbidities. However, some sporadic cases were also described in previously healthy people. We report a real-world experience about the management of cases of influenza admitted in a large teaching hospital in the Friuli Venezia Giulia region during the 2017-2018 influenza season. We also provide a practical guide for the management of hospitalized influenza cases. Methods. A retrospective observational analysis wasbconducted among all influenza cases requiring admission in our Center during the 2017-18 season. Results. Overall, 29 patients were admitted at the University Hospital of Udine during the 2017-18 season with a diagnosis of influenza. B virus was responsible for the majority of the cases. More than 65.5% of the subjects presented with a complication. We estimated that 41.4% of the admitted cases were affected by a “severe form”. All these cases required admission in Intensive Care Unit, 27.6% and 10.3% of them needing Oral-Tracheal Intubation and Extracorporeal Membrane Oxygenation, respectively. Fatality rate was 24.1%. Noteworthy, only 9 subjects of our cohort had received vaccination. On the basis of the experience acquired during the past season, we propose a practical guide to approach influenza cases in everyday hospital practice. Conclusion. The cornerstones of the management of all hospitalized influenza cases are the rapid identification and treatment of severe forms. Timely and strictly adherence to contact and respiratory precautions are also fundamental to reduce the risk of intra-hospital outbreaks. Despite the improvements of antiviral therapies and supportive measures, influenza-related morbidity and mortality remain high. According to our opinion, a universal vaccination program represents the only safe and effective method to fill the gap., Journal of Preventive Medicine and Hygiene, Vol 60 No 3 (2019): 2019603

BACKGROUND AND OBJECTIVES: Disease biomarkers require appropriate clinical context to be used effectively. Combining clinical risk factors, in addition to small changes in serum creatinine, has been proposed to improve the assessment of AKI. This notion was developed in order to identify the risk of AKI early in a patient's clinical course. We set out to assess the performance of this combination approach. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A secondary analysis of data from a prospective multicenter intensive care unit cohort study (September 2009 to April 2010) was performed. Patients at high risk using this combination approach were defined as an early increase in serum creatinine of 0.1-0.4 mg/dl, depending on number of clinical factors predisposing to AKI. AKI was defined and staged using the Acute Kidney Injury Network criteria. The primary outcome was evolution to severe AKI (Acute Kidney Injury Network stages 2 and 3) within 7 days in the intensive care unit. RESULTS: Of 506 patients, 214 (42.2%) patients had early creatinine elevation and were deemed at high risk for AKI. This group was more likely to subsequently develop the primary endpoint (16.4% versus 1.0% [not at high risk], P

PURPOSE: The decision to start venovenous extracorporeal membrane oxygenation (VV ECMO) is commonly based on the severity of respiratory failure, with little consideration of the extrapulmonary organ function. The aim of the study was to identify predictors of mortality and to develop a score allowing a better stratification of patients at the time of VV ECMO initiation. METHODS: This was a prospective multicenter cohort study on 60 patients with influenza A (H1N1)-associated respiratory distress syndrome participating in the Italian ECMOnet data set in the 2009 pandemic. Criteria for ECMO institution were standardized according to national guidelines. RESULTS: The survival rate in patients treated with ECMO was 68%. Significant predictors of death before ECMO institution by multivariate analysis were hospital length of stay before ECMO institution (OR=1.52, 95% CI 1.12-2.07, p=0.008); bilirubin (OR=2.32, 95% CI 1.52-3.52, p&nbsp

Introduction: Acute kidney injury requiring renal replacement therapy is a serious complication following cardiac surgery associated with poor clinical outcomes. Until now no drug showed nephroprotective effects. Fenoldopam is a dopamine-1 receptor agonist which seems to be effective in improving postoperative renal function. The aim of this paper is to describe the design of the FENO-HSR study, planned to assess the effect of a continuous infusion of fenoldopam in reducing the need for renal replacement therapy in patients with acute kidney injury after cardiac surgery. Methods: We're performing a double blind, placebo-controlled multicentre randomized trial in over 20 Italian hospitals. Patients who develop acute renal failure defined as R of RIFLE score following cardiac surgery are randomized to receive a 96-hours continuous infusion of either fenoldopam (0.025-0.3 µg/kg/min) or placebo. Results: The primary endpoint will be the rate of renal replacement therapy. Secondary endpoints will be: mortality, time on mechanical ventilation, length of intensive care unit and hospital stay, peak serum creatinine and the rate of acute renal failure (following the RIFLE score). Conclusions: This trial is planned to assess if fenoldopam could improve relevant outcomes in patients undergoing cardiac surgery who develop acute renal dysfunction. Results of this double-blind randomized trial could provide important insights to improve the management strategy of patients at high risk for postoperative acute kidney injury.

Acute renal failure (ARF) is s a major complication after cardiac surgery and its prevalence still remains high. Even minor changes in serum creatinine are related to an increase morbidity and mortality. Recently two consensus conferences have suggested new diagnostic criteria to define acute kidney injury and risk scores to better identify patients who will probably develop ARF after cardiac surgery. In fact a prompt recognition of high risk patients could allow a more aggressive therapy at a reversible stage of an incoming ARF. To date prophylactic strategies of renal function preservation during surgery include the avoidance of nephrotoxic insult and the prevention or correction of renal hypoperfusion. Although there are still no pharmacological agents able to prevent the perioperative ARF, several trials are investigating new pharmacological approaches. When prophylactic strategies fail and severe ARF occurs, renal replacement therapy becomes mandatory. The timing and the kind of renal replacement therapy remain an open issue. Further randomized case-control studies with adequate statistical power are needed to have more conclusive data. Aim of this paper is to start from the acute renal injury physiopathology to analyze the most common prophylactic and pharmacological strategies.

Introduction In ICUs, both fluid overload and oliguria are common complications associated with increased mortality among critically ill patients, particularly in acute kidney injury (AKI). Although fluid overload is an expected complication of oliguria, it remains unclear whether their effects on mortality are independent of each other. The aim of this study is to evaluate the impact of both fluid balance and urine volume on outcomes and determine whether they behave as independent predictors of mortality in adult ICU patients with AKI. Methods We performed a secondary analysis of data from a multicenter, prospective cohort study in 10 Italian ICUs. AKI was defined by renal sequential organ failure assessment (SOFA) score (creatinine >3.5 mg/dL or urine output (UO)

A medium fidelity and low cost training device for pilots, called the Multi Aircraft Training Environment (MATE), is developed to replace other low fidelity stand-alone training devices and integrate them into a flexible environment, primarily aimed attraining pilots in checklist procedures. The cockpit switches and instruments in MATE are computer-generated graphics. The graphics are back projected onto semi-transparent touch screen panels in a hybrid cockpit mock-up. Thus, the MATE is relativelycheap, it is always available, it is reconfigurable (e.g. between types of aircraft/models to be simulated) and with possibilities for including various forms of intelligent computer assistance. This training concept and the technology are not specific toaviation, but can be used to simulate various types of control panels in different domains. The training effectiveness of pilots' procedure training in the MATE prototype was compared with the effects of traditional training that included the use of realaircraft. The experimental group (EXP) trained the pre-start checklist and the engine start checklist for the Saab 340 commuter aircraft in a MATE prototype. The control group (CTR) trained the same procedures using the aircraft (a/c) for training the prestart and a desktop computer tool (power plant trainer) for training engine starts. Performance on the pre-start checklist was compared in a formal checkout that took place in the a/c. Performance on the engine start procedure was compared in a fullflight simulator (FFS). The conclusion was, firstly, that training in the MATE prototype can result in an equally good performance as the existing training (a/c and computer tools), provided that the MATE trainees are given time to familiarise themselveswith the a/c. Secondly, training in MATE can result in better performance during dynamic tasks, such as abnormal engine starts. This is promising for the further development of the MATE concept. A medium fidelity and low cost training device for pilots, called the Multi Aircraft Training Environment (MATE), is developed to replace other low fidelity stand-alone training devices and integrate them into a flexible environment, primarily aimed at training pilots in checklist procedures. The cockpit switches and instruments in MATE are computer-generated graphics. The graphics are back projected onto semi-transparent touch screen panels in a hybrid cockpit mock-up. Thus, the MATE is relatively cheap, it is always available, it is reconfigurable (e.g. between types of aircraft/models to be simulated) and with possibilities for including various forms of intelligent computer assistance. This training concept and the technology are not specific to aviation, but can be used to simulate various types of control panels in different domains. The training effectiveness of pilots’ procedure training in the MATE prototype was compared with the effects of traditional training that included the use of real aircraft. The experimental group (EXP) trained the pre-start checklist and the engine start checklist for the Saab 340 commuter aircraft in a MATE prototype. The control group (CTR) trained the same procedures using the aircraft (a/c) for training the pre start and a desktop computer tool (power plant trainer) for training engine starts. Performance on the pre-start checklist was compared in a formal checkout that took place in the a/c. Performance on the engine start procedure was compared in a full flight simulator (FFS). The conclusion was, firstly, that training in the MATE prototype can result in an equally good performance as the existing training (a/c and computer tools), provided that the MATE trainees are given time to familiarise themselves with the a/c. Secondly, training in MATE can result in better performance during dynamic tasks, such as abnormal engine starts. This is promising for the further development of the MATE concept.