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OBJECTIVES:. In patients with COVID-19 respiratory failure, controlled mechanical ventilation (CMV) is often necessary during the acute phases of the disease. Weaning from CMV to pressure support ventilation (PSV) is a key objective when the patient’s respiratory functions improve. Limited evidence exists regarding the factors predicting a successful transition to PSV and its impact on patient outcomes. DESIGN:. Retrospective observational cohort study. SETTING:. Twenty-four Italian ICUs from February 2020 to May 2020. PATIENTS:. Mechanically ventilated ICU patients with COVID-19-induced respiratory failure. INTERVENTION:. The transition period from CMV to PSV was evaluated. We defined it as “failure of assisted breathing” if the patient returned to CMV within the first 72 hours. MEASUREMENTS AND MAIN RESULTS:. Of 1260 ICU patients screened, 514 were included. Three hundred fifty-seven patients successfully made the transition to PSV, while 157 failed. Pao2/Fio2 ratio before the transition emerged as an independent predictor of a successful shift (odds ratio 1.00; 95% CI, 0.99–1.00; p = 0.003). Patients in the success group displayed a better trend in Pao2/Fio2, Paco2, plateau and peak pressure, and pH level. Subjects in the failure group exhibited higher ICU mortality (hazard ratio 2.08; 95% CI, 1.42–3.06; p < 0.001), an extended ICU length of stay (successful vs. failure 21 ± 14 vs. 27 ± 17 d; p < 0.001) and a longer duration of mechanical ventilation (19 ± 18 vs. 24 ± 17 d, p = 0.04). CONCLUSIONS:. Our study emphasizes that the Pao2/Fio2 ratio was the sole independent factor associated with a failed transition from CMV to PSV. The unsuccessful transition was associated with worse outcomes.

Few data are available on incidence of multidrug-resistant organism (MDRO) colonization and infections in mechanically ventilated patients, particularly during the COVID-19 pandemic. We retrospectively evaluated all patients admitted to the COVID-19 intensive care unit (ICU) of Hub Hospital in Milan, Italy, during October 2020‒May 2021. Microbiologic surveillance was standardized with active screening at admission and weekly during ICU stay. Of 435 patients, 88 (20.2%) had MDROs isolated ≤48 h after admission. Of the remaining patients, MDRO colonization was diagnosed in 173 (51.2%), MDRO infections in 95 (28.1%), and non-MDRO infections in 212 (62.7%). Non-MDRO infections occurred earlier than MDRO infections (6 days vs. 10 days; p

Abstract Background There is very limited evidence identifying factors that increase respiratory drive in hypoxemic intubated patients. Most physiological determinants of respiratory drive cannot be directly assessed at the bedside (e.g., neural inputs from chemo- or mechano-receptors), but clinical risk factors commonly measured in intubated patients could be correlated with increased drive. We aimed to identify clinical risk factors independently associated with increased respiratory drive in intubated hypoxemic patients. Methods We analyzed the physiological dataset from a multicenter trial on intubated hypoxemic patients on pressure support (PS). Patients with simultaneous assessment of the inspiratory drop in airway pressure at 0.1-s during an occlusion (P 0.1) and risk factors for increased respiratory drive on day 1 were included. We evaluated the independent correlation of the following clinical risk factors for increased drive with P 0.1: severity of lung injury (unilateral vs. bilateral pulmonary infiltrates, PaO2/FiO2, ventilatory ratio); arterial blood gases (PaO2, PaCO2 and pHa); sedation (RASS score and drug type); SOFA score; arterial lactate; ventilation settings (PEEP, level of PS, addition of sigh breaths). Results Two-hundred seventeen patients were included. Clinical risk factors independently correlated with higher P 0.1 were bilateral infiltrates (increase ratio [IR] 1.233, 95%CI 1.047–1.451, p = 0.012); lower PaO2/FiO2 (IR 0.998, 95%CI 0.997–0.999, p = 0.004); higher ventilatory ratio (IR 1.538, 95%CI 1.267–1.867, p

ObjectiveSepsis and septic shock are major challenges and economic burdens to healthcare, impacting millions of people globally and representing significant causes of mortality. Recently, a large number of quality improvement programs focused on sepsis resuscitation bundles have been instituted worldwide. These educational initiatives have been shown to be associated with improvements in clinical outcomes. We aimed to evaluate the impact of a multi-faceted quality implementing program (QIP) on the compliance of a “simplified 1-h bundle” (Sepsis 6) and hospital mortality of severe sepsis and septic shock patients out of the intensive care unit (ICU).MethodsEmergency departments (EDs) and medical wards (MWs) of 12 academic and non-academic hospitals in the Lombardy region (Northern Italy) were involved in a multi-faceted QIP, which included educational and organizational interventions. Patients with a clinical diagnosis of severe sepsis or septic shock according to the Sepsis-2 criteria were enrolled in two different periods: from May 2011 to November 2011 (before-QIP cohort) and from August 2012 to June 2013 (after-QIP cohort).Measurements and main resultsThe effect of QIP on bundle compliance and hospital mortality was evaluated in a before–after analysis. We enrolled 467 patients in the before-QIP group and 656 in the after-QIP group. At the time of enrollment, septic shock was diagnosed in 50% of patients, similarly between the two periods. In the after-QIP group, we observed increased compliance to the “simplified rapid (1 h) intervention bundle” (the Sepsis 6 bundle – S6) at three time-points evaluated (1 h, 13.7 to 18.7%, p = 0.018, 3 h, 37.1 to 48.0%, p = 0.013, overall study period, 46.2 to 57.9%, p

Abstract Background The role of upper airways microbiota and its association with ventilator-associated pneumonia (VAP) development in mechanically ventilated (MV) patients is unclear. Taking advantage of data collected in a prospective study aimed to assess the composition and over-time variation of upper airway microbiota in patients MV for non-pulmonary reasons, we describe upper airway microbiota characteristics among VAP and NO-VAP patients. Methods Exploratory analysis of data collected in a prospective observational study on patients intubated for non-pulmonary conditions. Microbiota analysis (trough 16S-rRNA gene profiling) was performed on endotracheal aspirates (at intubation, T0, and after 72 h, T3) of patients with VAP (cases cohort) and a subgroup of NO-VAP patients (control cohort, matched according to total intubation time). Results Samples from 13 VAP patients and 22 NO-VAP matched controls were analyzed. At intubation (T0), patients with VAP revealed a significantly lower microbial complexity of the microbiota of the upper airways compared to NO-VAP controls (alpha diversity index of 84 ± 37 and 160 ± 102, in VAP and NO_VAP group, respectively, p-value

Abstract Patients with acute pancreatitis (AP) often require ICU admission, especially when signs of multiorgan failure are present, a condition that defines AP as severe. This disease is characterized by a massive pancreatic release of pro-inflammatory cytokines that causes a systemic inflammatory response syndrome and a profound intravascular fluid loss. This leads to a mixed hypovolemic and distributive shock and ultimately to multiorgan failure. Aggressive fluid resuscitation is traditionally considered the mainstay treatment of AP. In fact, all available guidelines underline the importance of fluid therapy, particularly in the first 24–48 h after disease onset. However, there is currently no consensus neither about the type, nor about the optimal fluid rate, total volume, or goal of fluid administration. In general, a starting fluid rate of 5–10 ml/kg/h of Ringer’s lactate solution for the first 24 h has been recommended. Fluid administration should be aggressive in the first hours, and continued only for the appropriate time frame, being usually discontinued, or significantly reduced after the first 24–48 h after admission. Close clinical and hemodynamic monitoring along with the definition of clear resuscitation goals are fundamental. Generally accepted targets are urinary output, reversal of tachycardia and hypotension, and improvement of laboratory markers. However, the usefulness of different endpoints to guide fluid therapy is highly debated. The importance of close monitoring of fluid infusion and balance is acknowledged by most available guidelines to avoid the deleterious effect of fluid overload. Fluid therapy should be carefully tailored in patients with severe AP, as for other conditions frequently managed in the ICU requiring large fluid amounts, such as septic shock and burn injury. A combination of both noninvasive clinical and invasive hemodynamic parameters, and laboratory markers should guide clinicians in the early phase of severe AP to meet organ perfusion requirements with the proper administration of fluids while avoiding fluid overload. In this narrative review the most recent evidence about fluid therapy in severe AP is discussed and an operative algorithm for fluid administration based on an individualized approach is proposed.

Abstract Background Perchloroethylene is a colorless, strong-smelling substance commonly used for dry cleaning. Liver and kidney toxicities and carcinogenicity are well-known occupational hazards caused by chronic perchloroethylene exposure. Acute intoxication by ingestion of nondiluted perchloroethylene is rare in the adult population owing to its strong smell and taste. Very few data are available to physicians managing patients in this situation. Case presentation An 89-year-old Caucasian woman accidentally drank perchloroethylene while visiting her laundry, leading to a coma within a few minutes. The poison control center provided little information about perchloroethylene toxicity after ingestion, including an estimated long biological half-life (144 hour) and detrimental effects to liver and kidneys. A long intensive care unit stay was thus expected, potentially leading to several complications. After intubation, transitory hypoxemia appeared and rapidly resolved, while mild hemodynamic instability was managed with fluid resuscitation and anti-arrhythmic drugs. Twelve hours after perchloroethylene ingestion, the patient suddenly woke up and self-extubated. Less than 24 hours after ingestion, she was discharged from the intensive care unit, and 4 days later she was discharged home. Conclusion The patient drank perchloroethylene from a bottle, which prevented her from smelling it, and owing to its taste, only a small sip was likely drunk. However, a much larger intake was presumed, given her rapid and profound central nervous system depression. This case was challenging owing to the paucity of information available regarding acute perchloroethylene ingestion and the duration and magnitude of its effect. The present report will hopefully be of support for clinicians managing patients with this rare acute intoxication.

Introduction: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability. Methods: Sprague-Dawley rats underwent prolonged MV (5 hours). VIDD+Levo group received a starting bolus of levosimendan immediately after intratracheal intubation and then an intravenous infusion of levosimendan throughout the study. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis and Western blot analysis. Healthy rats were used as the control. Results: Levosimendan treatment maintained an adequate mean arterial pressure during the entire experimental protocol, preserved levels of autophagy-related proteins (LC3BI and LC3BII) and the muscular cell diameter demonstrated by histological analysis. Levosimendan did not affect the diaphragmatic contraction or the levels of proteins involved in the protein degradation (atrogin). Conclusions: Our data suggest that levosimendan preserves muscular cell structure (cross-sectional area) and muscle autophagy after 5 hours of MV in a rat model of VIDD. However, levosimendan did not improve diaphragm contractile efficiency.

Summary: Background: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. Methods: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. Findings: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18–4.90]). No adverse events were reported. Interpretation: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. Trial registration: NCT03237910. Funding: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Prehospital field triage often fails to accurately identify the need for emergent surgical or non-surgical procedures, resulting in inefficient resource utilization and increased costs. This study aimed to analyze prehospital factors associated with the need for emergent procedures (such as surgery or interventional angiography) within 6 h of hospital admission. Additionally, our goal was to develop a prehospital triage tool capable of estimating the likelihood of requiring an emergent procedure following hospital admission. We conducted a retrospective observational study, analyzing both prehospital and in-hospital data obtained from the Lombardy Trauma Registry. We conducted a multivariable logistic regression analysis to identify independent predictors of emergency procedures within the first 6 h from admission. Subsequently, we developed and internally validated a triage score composed of factors associated with the probability of requiring an emergency procedure. The study included a total of 3985 patients, among whom 295 (7.4%) required an emergent procedure within 6 h. Age, penetrating injury, downfall, cardiac arrest, poor neurological status, endotracheal intubation, systolic pressure, diastolic pressure, shock index, respiratory rate and tachycardia were identified as predictors of requiring an emergency procedure. A triage score generated from these predictors showed a good predictive power (AUC of the ROC curve: 0.81) to identify patients requiring an emergent surgical or non-surgical procedure within 6 h from hospital admission. The proposed triage score might contribute to predicting the need for immediate resource availability in trauma patients.

Abstract Background During the first coronavirus disease 2019 (COVID-19) pandemic wave, an unprecedented number of patients with respiratory failure due to a new, highly contagious virus needed hospitalization and intensive care unit (ICU) admission. The aim of the present study was to describe the communication and visiting policies of Italian intensive care units (ICUs) during the first COVID-19 pandemic wave and national lockdown and compare these data with prepandemic conditions. Methods A national web-based survey was conducted among 290 Italian hospitals. Each ICU (active between February 24 and May 31, 2020) was encouraged to complete an individual questionnaire inquiring the hospital/ICU structure/organization, communication/visiting habits and the role of clinical psychology prior to, and during the first COVID-19 pandemic wave. Results Two hundred and nine ICUs from 154 hospitals (53% of the contacted hospitals) completed the survey (202 adult and 7 pediatric ICUs). Among adult ICUs, 60% were dedicated to COVID-19 patients, 21% were dedicated to patients without COVID-19 and 19% were dedicated to both categories (Mixed). A total of 11,102 adult patients were admitted to the participating ICUs during the study period and only approximately 6% of patients received at least one visit. Communication with family members was guaranteed daily through an increased use of electronic devices and was preferentially addressed to the same family member. Compared to the prepandemic period, clinical psychologists supported physicians more often regarding communication with family members. Fewer patients received at least one visit from family members in COVID and mixed-ICUs than in non-COVID ICUs, l (0 [0–6]%, 0 [0–4]% and 11 [2–25]%, respectively, p

Abstract Background External chest-wall compression (ECC) is sometimes used in ARDS patients despite lack of evidence. It is currently unknown whether this practice has any clinical benefit in patients with COVID-19 ARDS (C-ARDS) characterized by a respiratory system compliance (C rs)

Abstract Background Septic shock is a severe form of sepsis marked by hypotension with an ominous outcome despite the introduction of modern intensive care. The aim of the present study is to obtain a panel with biomarkers, echocardiographic and vascular parameters to better risk stratify patients and identify those at higher risk of ominous outcome. Methods Between May 2013 and April 2016, 35 consecutive patients admitted at the Intensive Care Unit (ICU) of ASST Great Metropolitan Hospital Niguarda with the diagnosis of severe sepsis or septic shock were enrolled. All patients underwent rest echocardiography and several circulating biomarkers of myocardial damage or oxidative stress. Results The multivariate Cox’s proportional hazard model showed that the only independent prognostic predictor for 30-day mortality was the angiopoietin-2, (HR 1.017, 95% CI 1.000–1.034; P = 0.049). An angiopoietin-2 concentrations ≥ of 33,418 pg/mL was identified as the optimal threshold for the discrimination between survivors and non survivors at the time of admission in ICU, with a sensitivity of 80% and a specificity of 68%. Conclusions Septic shock has a poor in-hospital outcome even when the best of care is implemented. Among the biochemical parameters angiopoietin was able to identify patients at risk of death. The lowest the value at admission, the highest the risk of in-hospital death. No echocardiographic nor vascular parameter was able to predict outcome in this setting.

BackgroundRespiratory physiotherapy is reported as safe and feasible in mechanically ventilated patients with severe Coronavirus Disease (COVID-19) admitted to Intensive Care Unit (ICU), but the short-term benefits remain unclear.MethodsWe performed a retrospective observational study in four ICUs in Northern Italy. All patients with COVID-19 admitted to ICU and under invasive mechanical ventilation (MV) between March 1st and May 30th, 2020, were enrolled into the study. Overlap weighting based on the propensity score was used to adjust for confounding in the comparison of patients who had or had not been treated by physiotherapists. The primary outcome was the number of days alive and ventilator-free (VFDs). The secondary outcomes were arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio (P/F) at ICU discharge, ICU length of stay, ICU and hospital mortality, and survival at 90 days. The trial protocol was registered on clinicaltrials.gov (NCT 05067907).ResultsA total of 317 patients were included in the analysis. The median VFDs was 18 days [interquartile range (IQR) 10; 24] in patients performing physiotherapy and 21 days (IQR 0; 26) in the group without physiotherapy [incidence rate ratio (IRR) 0.86, 95% confidence interval (CI): 0.78; 0.95]. The chance of 0 VFDs was lower for patients treated by physiotherapists compared to those who were not [odds ratio (OR) = 0.36, 95% CI: 0.18–0.71]. Survival at 90 days was 96.0% in the physiotherapy group and 70.6% in patients not performing physiotherapy [hazard ratio (HR) = 0.14, 95% CI: 0.03–0.71]. Number of VFDs was not associated with body mass index (BMI), sex, or P/F at ICU admission for individuals with at least 1 day off the ventilator.ConclusionIn patients with COVID-19 admitted to ICU during the first pandemic wave and treated by physiotherapists, the number of days alive and free from MV was lower compared to patients who did not perform respiratory physiotherapy. Survival at 90 days in the physiotherapy group was greater compared to no physiotherapy. These findings may be the starting point for further investigation in this setting.

Background: Changing trunk inclination affects lung function in patients with ARDS. However, its impacts on PEEP titration remain unknown. The primary aim of this study was to assess, in mechanically ventilated patients with COVID-19 ARDS, the effects of trunk inclination on PEEP titration. The secondary aim was to compare respiratory mechanics and gas exchange in the semi-recumbent (40° head-of-the-bed) and supine-flat (0°) positions following PEEP titration. Methods: Twelve patients were positioned both at 40° and 0° trunk inclination (randomized order). The PEEP associated with the best compromise between overdistension and collapse guided by Electrical Impedance Tomography (PEEPEIT) was set. After 30 min of controlled mechanical ventilation, data regarding respiratory mechanics, gas exchange, and EIT parameters were collected. The same procedure was repeated for the other trunk inclination. Results: PEEPEIT was lower in the semi-recumbent than in the supine-flat position (8 ± 2 vs. 13 ± 2 cmH2O, p < 0.001). A semi-recumbent position with optimized PEEP resulted in higher PaO2:FiO2 (141 ± 46 vs. 196 ± 99, p = 0.02) and a lower global inhomogeneity index (46 ± 10 vs. 53 ± 11, p = 0.008). After 30 min of observation, a loss of aeration (measured by EIT) was observed only in the supine-flat position (−153 ± 162 vs. 27 ± 203 mL, p = 0.007). Conclusions: A semi-recumbent position is associated with lower PEEPEIT and results in better oxygenation, less derecruitment, and more homogenous ventilation compared to the supine-flat position.

Abstract Background The surge of critically ill patients due to the coronavirus disease-2019 (COVID-19) overwhelmed critical care capacity in areas of northern Italy. Anesthesia machines have been used as alternatives to traditional ICU mechanical ventilators. However, the outcomes for patients with COVID-19 respiratory failure cared for with Anesthesia Machines is currently unknow. We hypothesized that COVID-19 patients receiving care with Anesthesia Machines would have worse outcomes compared to standard practice. Methods We designed a retrospective study of patients admitted with a confirmed COVID-19 diagnosis at a large tertiary urban hospital in northern Italy. Two care units were included: a 27-bed standard ICU and a 15-bed temporary unit emergently opened in an operating room setting. Intubated patients assigned to Anesthesia Machines (AM group) were compared to a control cohort treated with standard mechanical ventilators (ICU-VENT group). Outcomes were assessed at 60-day follow-up. A multivariable Cox regression analysis of risk factors between survivors and non-survivors was conducted to determine the adjusted risk of death for patients assigned to AM group. Results Complete daily data from 89 mechanically ventilated patients consecutively admitted to the two units were analyzed. Seventeen patients were included in the AM group, whereas 72 were in the ICU-VENT group. Disease severity and intensity of treatment were comparable between the two groups. The 60-day mortality was significantly higher in the AM group compared to the ICU-vent group (12/17 vs. 27/72, 70.6% vs. 37.5%, respectively, p = 0.016). Allocation to AM group was associated with a significantly increased risk of death after adjusting for covariates (HR 4.05, 95% CI: 1.75–9.33, p = 0.001). Several incidents and complications were reported with Anesthesia Machine care, raising safety concerns. Conclusions Our results support the hypothesis that care associated with the use of Anesthesia Machines is inadequate to provide long-term critical care to patients with COVID-19. Added safety risks must be considered if no other option is available to treat severely ill patients during the ongoing pandemic. Clinical trial number Not applicable.

Abstract 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

BackgroundAdvances in regional anesthesia and pain management led to the advent of ultrasound-guided fascial plane blocks, which represent a new and promising route for the administration of local anesthetics. Both practical and theoretical knowledge of locoregional anesthesia are therefore becoming fundamental, requiring specific training programs for residents. Simulation-based medical education and training (SBET) has been recently applied to ultrasound-guided regional anesthesia (UGRA) with remarkable results. With this in mind, the anesthesia and intensive care residency program of the University of Milano-Bicocca organized a 4-h regional anesthesia training workshop with the BlockSim® (Accurate Srl, Cesena) simulator. Our study aimed to measure the residents' improvement in terms of reduction in time required to achieve an erector spinae plane (ESP) block.MethodsFifty-two first-year anesthesia residents were exposed to a 4-h training workshop focused on peripheral blocks. The course included an introductory theoretical session held by a locoregional anesthetist expert, a practical training on human models and mannequins using Onvision® (B. Braun, Milano) technologies, and two test performances on the BlockSim simulator. Residents were asked to perform two ESP blocks on the BlockSim: the first without previous practice on the simulator, the second at the end of the course. Trainees were also also asked to complete a self-assessment questionnaire.ResultsThe time needed to achieve the block during the second attempt was significantly shorter (131 [83, 198] vs. 68 [27, 91] s, p < 0.001). We also observed a reduction in the number of needle insertions from 3 [2, 7] to 2 [1, 4] (p = 0.002), and an improvement aiming correctly at the ESP from 30 (58%) to 46 (88%) (p < 0.001). Forty-nine (94%) of the residents reported to have improved their regional anesthesia knowledge, 38 (73%) perceived an improvement in their technical skills and 46 (88%) of the trainees declared to be “satisfied/very satisfied” with the course.ConclusionsA 4-h hands-on course based on SBET may enhance first-year residents' UGRA ability, decrease the number of punctures and time needed to perform the ESP block, and improve the correct aim of the fascia.

The Lombardy region of Italy was heavily affected early in the SARS-CoV-2 pandemic. Here, the authors use whole genome sequencing and show that there were multiple introductions into the region, with transmission occurring before the first case was detected.

The strange metallic state of cuprates occurring in a broad region of their phase diagram outside the superconducting and pseudogapped regions remains a mystery. Here the authors consider the charge density fluctuations recently discovered in resonant X-ray experiments as a possible source of scattering and show that these fluctuations can account for the strange metallic behavior.

Abstract Background Reverse Transcription-Polymerase Chain Reaction (RT-PCR) for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) diagnosis currently requires quite a long time span. A quicker and more efficient diagnostic tool in emergency departments could improve management during this global crisis. Our main goal was assessing the accuracy of artificial intelligence in predicting the results of RT-PCR for SARS-COV-2, using basic information at hand in all emergency departments. Methods This is a retrospective study carried out between February 22, 2020 and March 16, 2020 in one of the main hospitals in Milan, Italy. We screened for eligibility all patients admitted with influenza-like symptoms tested for SARS-COV-2. Patients under 12 years old and patients in whom the leukocyte formula was not performed in the ED were excluded. Input data through artificial intelligence were made up of a combination of clinical, radiological and routine laboratory data upon hospital admission. Different Machine Learning algorithms available on WEKA data mining software and on Semeion Research Centre depository were trained using both the Training and Testing and the K-fold cross-validation protocol. Results Among 199 patients subject to study (median [interquartile range] age 65 [46–78] years; 127 [63.8%] men), 124 [62.3%] resulted positive to SARS-COV-2. The best Machine Learning System reached an accuracy of 91.4% with 94.1% sensitivity and 88.7% specificity. Conclusion Our study suggests that properly trained artificial intelligence algorithms may be able to predict correct results in RT-PCR for SARS-COV-2, using basic clinical data. If confirmed, on a larger-scale study, this approach could have important clinical and organizational implications.

Abstract Coronavirus disease 2019 (COVID‐19) patients with cardiac injury have an increased risk of mortality. It remains to be determined the mechanism of cardiac injury and the identification of specific conditions that affect the heart during COVID‐19. We present the case of a 76‐year‐old woman with COVID‐19 pneumonia that developed a takotsubo syndrome (TTS). Although the patient presented normal left ventricular ejection fraction and normal levels of troponin on admission, after 16 days in intensive care unit due to respiratory distress, she suddenly developed cardiogenic shock. Shock occurred few hours after a spontaneous breathing trial through her tracheostomy. Bed‐side echocardiographic revealed apical ballooning promptly supporting the diagnosis of TTS. She was successfully treated with deep sedation and low dosage of epinephrine. The relevance of this case is that TTS can occur in the late phase of COVID‐19. Awareness of late TTS and bed‐side echocardiographic evaluation can lead to prompt identification and treatment.

Abstract Background A Covid-19 outbreak developed in Lombardy, Veneto and Emilia-Romagna (Italy) at the end of February 2020. Fear of an imminent saturation of available ICU beds generated the notion that rationing of intensive care resources could have been necessary. Results In order to evaluate the impact of Covid-19 on the ICU capacity to manage critically ill patients, we performed a retrospective analysis of the first 2 weeks of the outbreak (February 24–March 8). Data were collected from regional registries and from a case report form sent to participating sites. ICU beds increased from 1545 to 1989 (28.7%), and patients receiving respiratory support outside the ICU increased from 4 (0.6%) to 260 (37.0%). Patients receiving respiratory support outside the ICU were significantly older [65 vs. 77 years], had more cerebrovascular (5.8 vs. 13.1%) and renal (5.3 vs. 10.0%) comorbidities and less obesity (31.4 vs. 15.5%) than patients admitted to the ICU. PaO2/FiO2 ratio, respiratory rate and arterial pH were higher [165 vs. 244; 20 vs. 24 breath/min; 7.40 vs. 7.46] and PaCO2 and base excess were lower [34 vs. 42 mmHg; 0.60 vs. 1.30] in patients receiving respiratory support outside the ICU than in patients admitted to the ICU, respectively. Conclusions Increase in ICU beds and use of out-of-ICU respiratory support allowed effective management of the first 14 days of the Covid-19 outbreak, avoiding resource rationing.

Abstract Background Pendelluft, the movement of gas within different lung regions, is present in animal models of assisted mechanical ventilation and associated with lung overstretching. Due to rebreathing of CO2 as compared to fresh gas, pendelluft might reduce ventilatory efficiency possibly exacerbating patient’s respiratory workload during weaning. Our aim was to measure pendelluft by electrical impedance tomography (EIT) in patients who failed a spontaneous breathing trial (SBT). Methods This is an observational study conducted in a general intensive care unit of a tertiary-level teaching hospital. EIT signal was recorded in 20 patients while pressure support (PS) ventilation was progressively reduced from clinical level (baseline) to 2 cmH2O, as in an SBT; four ventral-to-dorsal lung regions of interest were identified for pendelluft measurement. A regional gas movement (> 6 mL) occurring in a direction opposite to the global EIT signal was considered diagnostic for high pendelluft. Results Eight patients out of 20 (40%) were classified as high-pendelluft; baseline clinical characteristics did not differ between high- and low-pendelluft patients. At PS reduction, pendelluft and EtCO2 increased more in the high-pendelluft group (p

Abstract Background Diaphragm atrophy and dysfunction are consequences of mechanical ventilation and are determinants of clinical outcomes. We hypothesize that partial preservation of diaphragm function, such as during assisted modes of ventilation, will restore diaphragm thickness. We also aim to correlate the changes in diaphragm thickness and function to outcomes and clinical factors. Methods This is a prospective, multicentre, observational study. Patients mechanically ventilated for more than 48 h in controlled mode and eventually switched to assisted ventilation were enrolled. Diaphragm ultrasound and clinical data collection were performed every 48 h until discharge or death. A threshold of 10% was used to define thinning during controlled and recovery of thickness during assisted ventilation. Patients were also classified based on the level of diaphragm activity during assisted ventilation. We evaluated the association between changes in diaphragm thickness and activity and clinical outcomes and data, such as ventilation parameters. Results Sixty-two patients ventilated in controlled mode and then switched to the assisted mode of ventilation were enrolled. Diaphragm thickness significantly decreased during controlled ventilation (1.84 ± 0.44 to 1.49 ± 0.37 mm, p

The severe acute respiratory syndrome coronavirus SARS-CoV2 is spreading over millions of people worldwide, leading to thousands of deaths, even among the healthcare providers. Italy has registered the deaths of 337 physicians and more than 200 nurses as of March 14, 2021. Anesthesiologists are at higher risk as they are the care providers in both ICU and operating rooms.Although the vaccination of healthcare providers has been the prioirity, physicians are still continually exposed to the virus and potentially risk contagion and must thus protect themselves and their patients from the risks of infection while providing the best care to their surgical patients.Regional anesthesia allows for a reduction in airway manipulation, reducing environmental contamination as a result. Furthermore, regional anesthesia reduces the opioid requirements as well as the muscle paralysis due to muscle-relaxants and should be recommended whenever possible in COVID-19 patients. Our aim is to evaluate the advantages and criticisms of regional anesthesia in the management of surgical patients in the pandemic age.

Background: Though variable, many major metropolitan cities reported profound and unprecedented increases in out-of-hospital cardiac arrest (OHCA) in early 2020. This study examined the relative magnitude of those increases and their relationship to COVID-19 prevalence. Methods: EMS (9-1-1 system) medical directors for 50 of the largest U.S. cities agreed to provide the aggregate, de-identified, pre-existing monthly tallies of OHCA among adults (age >18 years) occurring between January and June 2020 within their respective jurisdictions. Identical comparison data were also provided for corresponding time periods in 2018 and 2019. Equivalent data were obtained from the largest cities in Italy, United Kingdom and France, as well as Perth, Australia and Auckland, New Zealand. Findings: Significant OHCA escalations generally paralleled local prevalence of COVID-19. During April, most U.S. cities (34/50) had >20% increases in OHCA versus 2018–2019 which reflected high local COVID-19 prevalence. Thirteen observed 1·5-fold increases in OHCA and three COVID-19 epicenters had >100% increases (2·5-fold in New York City). Conversely, cities with lesser COVID-19 impact observed unchanged (or even diminished) OHCA numbers. Altogether (n = 50), on average, OHCA cases/city rose 59% during April (p = 0·03). By June, however, after mitigating COVID-19 spread, cities with the highest OHCA escalations returned to (or approached) pre-COVID OHCA numbers while cities minimally affected by COVID-19 during April (and not experiencing OHCA increases), then had marked OHCA escalations when COVID-19 began to surge locally. European, Australian, and New Zealand cities mirrored the U.S. experience. Interpretation: Most metropolitan cities experienced profound escalations of OHCA generally paralleling local prevalence of COVID-19. Most of these patients were pronounced dead without COVID-19 testing. Funding: No funding was involved. Cities provided de-identified aggregate data collected routinely for standard quality assurance functions.

In severe acute respiratory distress syndrome (ARDS), characterized by the ratio of arterial partial pressure of oxygen over fraction of inspired oxygen (P/F) less than 150 mm Hg, pronation cycles are the only intervention that showed improved survival, in combination with protective ventilation. The physiological advantages of performing pronation cycles, such as the improvement of oxygenation, better tidal volume distribution with increased involvement of dorsal regions, and easier drainage of secretions, overcome the possible complications, that is, endotracheal tube occlusion or misplacement, pressure ulcers, and brachial plexus injury. However, the incidence of complications is dramatically lower in intensive care units with expertise, adopting prone positioning in daily practice. In this video we are proposing step by step an easy and ergonomic technique to perform pronation maneuvers in patients with severe ARDS. Recent literature suggests that a high percentage of these patients are treated without undergoing pronation cycles. The main purpose of this video is to help increase the number of intensive care units worldwide commonly performing pronation cycles in patients that have indications to be pronated, in order to decrease healthcare burden and costs directly caused by ARDS. Proper intensive care unit staff training is fundamental in minimizing the risks associated with the maneuver for both patients and operators; and diffusion of a safe technique encouraging the operators is the second main purpose of this video.

ObjectiveThrough a hospital-based SARS-CoV-2 molecular and serological screening, we evaluated the effectiveness of two months of lockdown and two of surveillance, in Milan, Lombardy, the first to be overwhelmed by COVID-19 pandemics during March-April 2020.MethodsAll subjects presenting at the major hospital of Milan from May-11 to July-5, 2020, underwent a serological screening by chemiluminescent assays. Those admitted were further tested by RT-PCR.ResultsThe cumulative anti-N IgG seroprevalence in the 2753 subjects analyzed was of 5.1% (95%CI = 4.3%-6.0%), with a peak of 8.4% (6.1%-11.4%) 60-63 days since the peak of diagnoses (March-20). 31/106 (29.2%) anti-N reactive subjects had anti-S1/S2 titers >80 AU/mL. Being tested from May-18 to June-5, or residing in the provinces with higher SARS-CoV-2 circulation, were positively and independently associated with anti-N IgG reactivity (OR [95%CI]: 2.179[1.455-3.264] and 3.127[1.18-8.29], respectively). In the 18 RT-PCR positive, symptomatic subjects, anti-N seroprevalence was 33.3% (95% CI: 14.8%-56.3%).ConclusionSARS-CoV-2 seroprevalence in Milan is low, and in a downward trend after only 60-63 days since the peak of diagnoses. Italian confinement measures were effective, but the risk of contagion remains concrete. In hospital-settings, the performance of molecular and serological screenings upon admission remains highly advisable.

Since SARS-CoV-2-based disease (COVID-19) spreads as a pandemic, the necessity of a highly sensitive molecular diagnosis that can drastically reduce false negatives reverse transcription PCR (rtPCR) results, raises as a major clinical need. Here we evaluated the performance of a ddPCR-based assay to quantify SARS-CoV-2 titer in 55 suspected COVID-19 cases with negative rtPCR results thanks to in-house ddPCR assay (targeting RdRp and host RNaseP). Samples were collected at ASST-GOM Niguarda between February and May 2020 at hospital admission. Clinical and imaging data were obtained for clinical staging and definition of disease severity. Patients were mainly female (45.5%) with a median age of 73 (57-84) years. ddPCR-based assay detected SARS-CoV-2 genome in nasopharyngeal samples of 19 (34.5%) patients (median viral-load: 128 copies/mL, IQR: 72-345). In 15 of them (78.9%), chest CT showed a classical COVID-19 bilateral interstitial pneumonia; 14 patients (73.7%) showed severe COVID-19 manifestations. ddPCR did not identify any trace of SARS-CoV-2 genome in the respiratory samples of the remaining 36 patients. The serological assay performed in a subgroup of 34 patients at the later stage of illness (from 3 days to 90 days after) confirmed the presence of SARS-CoV-2 antibodies in all patients tested positive for SARS-CoV-2 in ddPCR (100%). Contrariwise, negative tests were observed in 95.0% ddPCR negative patients (P

Abstract Background A reanalysis of the ALBIOS trial suggested that patients with septic shock - defined by vasopressor-dependent hypotension in the presence of severe sepsis (Shock-2) - had a survival benefit when treated with albumin. The new septic shock definition (Shock-3) added the criterion of a lactate threshold of 2 mmol/L. We investigated how the populations defined according to Shock-2 and Shock-3 differed and whether the albumin benefit would be confirmed. Methods This is a retrospective analysis of the ALBIOS study, a randomized controlled study conducted between 2008 and 2012 in 100 intensive care units in Italy comparing the administration of 20% albumin and crystalloids versus crystalloids alone in patients with severe sepsis or septic shock. We analyzed data from 1741 patients from ALBIOS with serum lactate measurement available at baseline. We compared group size, physiological variables and 90-day mortality between patients defined by Shock-2 and Shock-3 and between the albumin and crystalloid treatment groups. Results We compared the Shock-2 and the Shock-3 definitions and the albumin and crystalloid treatment groups in terms of group size and physiological, laboratory and outcome variables. The Shock-3 definition reduced the population with shock by 34%. The Shock-3 group had higher lactate (p

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A “training sample” (March–June 2020) and a “testing sample” (September 2020–January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO2/FiO2 ratio, and sample (training/testing). “Training” and “testing” samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH2O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH2O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

Opioids are extensively used in patients with cancer pain; despite their efficacy, several patients can experience ineffective analgesia and/or side effects. Pharmacogenetics is a new approach to drug prescription based on the “personalized-medicine” concept, i.e., the ability of tailoring treatments to each individual’s genetic/genomic profile. Pharmacogenetics aims to identify specific genetic variants that influence pharmacokinetics and pharmacodynamics of drugs, better determining their effectiveness/safety profile. Opioid response is a complex scenario, but some gene variants have shown a correlation with pain sensitivity, as well as with opioid metabolism and clinical efficacy/adverse events. Although questions remain unanswered, some of these gene variants may already be used to identify specific patients’ phenotypes that are more prone to experience better clinical response (i.e., better analgesia and/or less adverse events). Once adopted, this approach to opioid prescription may improve a patient’s outcome. This review summarizes the available data on genetic variants and opioid response: we will focus on basic pharmacogenetic and its impact in the clinical scenario discussing how they may lead to more appropriate opioid prescription in cancer patients.

The coupling between lattice vibration quanta and valence electrons can induce charge-density modulations and decisively influence the transport properties of materials, e.g., leading to conventional superconductivity. In high-critical-temperature superconductors, where electronic correlation is the main actor, the actual role of electron-phonon coupling (EPC) is being intensely debated theoretically and investigated experimentally. We present an in-depth study of how the EPC strength can be obtained directly from resonant inelastic x-ray scattering (RIXS) data through the theoretical approach derived by Ament et al. [Europhys. Lett. 95, 27008 (2011)EULEEJ0295-507510.1209/0295-5075/95/27008]. The role of the model parameters (e.g., phonon energy ω_{0}, intermediate state lifetime 1/Γ, EPC matrix element M, and detuning energy Ω) is thoroughly analyzed, providing general relations among them that can be used to make quantitative estimates of the dimensionless EPC g=(M/ω_{0})^{2} without detailed microscopic modeling. We then apply these methods to very high-resolution Cu L_{3}-edge RIXS spectra of three Nd_{1+x}Ba_{2−x}Cu_{3}O_{7−δ} films. For the insulating antiferromagnetic parent compound, the value of M as a function of the in-plane momentum transfer is obtained for Cu-O bond-stretching (breathing) and bond-bending (buckling) phonon branches. For the underdoped and the nearly optimally doped samples, the effects of Coulomb screening and of charge-density-wave correlations on M are assessed. In light of the anticipated further improvements of the RIXS experimental resolution, this work provides a solid framework for an exhaustive investigation of the EPC in cuprates and other quantum materials.

INTRODUCTION:ABO blood type A was reported to correlate with an increased risk of acute respiratory distress syndrome (ARDS) in white patients with severe sepsis and major trauma compared with patients with other blood types. Information regarding ABO phenotypes and major outcomes in patients with ARDS is unavailable. The primary aim was to determine the relationship between ABO blood type A and intensive care unit (ICU) mortality in patients with acute hypoxemic respiratory failure (AHRF). The secondary aim was to describe the association between ABO blood type A and ICU length of stay (LOS) in this study population. METHODS:In a multicenter, retrospective cohort study, we collected the clinical records of patients admitted from January 2012 to December 2014 in five ICUs of Northern Italy. We included adult white patients admitted to the ICU who were diagnosed with AHRF requiring mechanical ventilation. RESULTS:The electronic records of 1732 patients with AHRF were reviewed. The proportion of patients with ABO blood type A versus other blood types was 39.9% versus 60.1%. ICU mortality (25%) and ICU LOS (median [interquartile range], 5 [2-12] days) were not different when stratified by ABO blood type (ICU mortality, overall p value = 0.905; ICU LOS, overall p value = 0.609). SAPSII was a positive predictor of ICU mortality (odds ration [OR], 32.80; 95% confidence interval [CI], 18.80-57.24; p < 0.001) and ICU LOS (β coefficient, 0.55; 95% CI, 0.35-0.75; p < 0.001) at multivariate analyses, whereas ABO blood type did not predict ICU outcome when forced into the model. CONCLUSION:ABO blood type did not correlate with ICU mortality and ICU LOS in adult patients with AHRF who were mechanically ventilated.

A pandemic (H1N1) 2009 virus strain carrying the D222G mutation was identified in a severely ill man and was transmitted to a household contact. Only mild illness developed in the contact, despite his obesity and diabetes. The isolated virus reacted fully with an antiserum against the pandemic vaccine strain.