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Background: Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes. Methods: This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories. Results: Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar–hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables. Conclusions: Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure. Trial registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.

Background: In patients with pneumonia or acute respiratory distress syndrome who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients. Methods: Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave. Results: A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). In-hospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19; 95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52; 95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93; 95% CI 1.45-16.75, p-value=0.010), and presence of active cancer (HR 3.64; 95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity. Conclusions: One-year post-discharge mortality depends on underlying patients’ comorbidities rather than COVID-19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients.

Barotrauma occurs in a significant number of patients with COVID-19 interstitial pneumonia undergoing mechanical ventilation. The aim of the current study was to investigate whether the Brixia score (BS) calculated on chest-X-rays acquired at the Emergency Room was associated with barotrauma. We retrospectively evaluated 117 SARS-CoV-2 patients presented to the Emergency Department (ED) and then admitted to the intensive care unit (ICU) for mechanical ventilation between February and April 2020. Subjects were divided into two groups according to the occurrence of barotrauma during their hospitalization. CXRs performed at ED admittance were assessed using the Brixia score. Distribution of barotrauma (pneumomediastinum, pneumothorax, subcutaneous emphysema) was identified in chest CT scans. Thirty-eight subjects (32.5%) developed barotrauma (25 pneumomediastinum, 24 pneumothorax, 24 subcutaneous emphysema). In the barotrauma group we observed higher Brixia score values compared to the non-barotrauma group (mean value 12.18 vs. 9.28), and logistic regression analysis confirmed that Brixia score is associated with the risk of barotrauma. In this work, we also evaluated the relationship between barotrauma and clinical and ventilatory parameters: SOFA score calculated at ICU admittance and number of days of non-invasive ventilation (NIV) prior to intubation emerged as other potential predictors of barotrauma.

Prone positioning is frequently used for non-intubated hypoxemic patients with COVID-19, although conclusive evidence is still lacking. The aim of the present study was to investigate whether baseline CT-scans could predict the improvement in oxygenation in COVID-19 related Acute respira-tory syndrome (ARDS) patients when pronated. Methods: A retrospective study of COVID-19 patients who underwent non-invasive ventilation (NIV) and prone positioning was conducted. Results: Forty-five patients were included. On average, 50% of the overall lung volume was affected by the disease, as observed in the CT-scans, with ground glass opacities (GGOs) and consolidations accounting for 44% and 4%, respectively. The abnormalities were mainly posterior, as demonstrated by posterior/anterior distribution ratios of 1.5 and 4.4 for GGO and consolidation, respectively. The median PaO2/FiO2 ratio during NIV in a supine position (SP1) was 140 [IQR 108–169], which improved by 67% (+98) during prone positioning, on average. Once supine positioning was resumed (SP2), the improvement in oxygenation was maintained in 28 patients (62% of the overall population, categorized as “responders”). We found no significant differences between responders and non-responders in terms of the extent (p = 0.92) and the distribution of parenchymal abnormalities seen in the baseline CT (p = 0.526). Conclusion: Despite the lack of a priori estimation of the sample size, considering the absence of any trends in the differences and correlations, we can reasonably conclude that the baseline chest CT-scan does not predict a gas-exchange response in awake prone-positioned patients with COVID-19 related ARDS. Physicians dealing with this category of patients should not rely on the imaging at presentation when evaluating whether to pronate patients.

The novel coronavirus, SARS-CoV-2, continues to spread rapidly. Here we discuss the dramatic situation created by COVID-19 in Italy, particularly in the province of Bergamo (the most severely affected in the first wave), as an example of how, in the face of an unprecedented tragedy, acting (albeit belatedly)—including imposing a very strict lockdown—can largely resolve the situation within approximately 2 months. The measures taken here ensured that Bergamo hospital, which was confronted with rapidly rising numbers of severely ill COVID-19 patients requiring hospitalization, was able to meet the initial challenges of the pandemic. We also report that local organization and, more important, the large natural immunity against SARS-CoV-2 of the Bergamo population developed during the first wave of the epidemic, can explain the limited number of new COVID-19 cases during the more recent second wave compared to the numbers in other areas of Lombardy. Furthermore, we highlight the importance of coordinating the easing of containment measures to avoid what is currently observed in other countries, especially in the United States, Latin American and India, where this approach has not been adopted, and a dramatic resurgence of COVID-19 cases and an increase in the number of hospitalisations and deaths have been reported.

The introduction of synthetic opioids in clinical practice played a major role in the history of anesthesiology. For years, anesthesiologists have been thinking that opioids are needed for intraoperative anesthesia. However, we now know that opioids (especially synthetic short-acting molecules) are definitely not ideal analgesics and may even be counterproductive, increasing postoperative pain. As well, opioids have revealed important drawbacks associated to poor perioperative outcomes. As a matter of fact, efforts in postoperative pain management in the last 30 years were driven by the idea of reducing/eliminating opioids from the postoperative period. However, a modern concept of anesthesia should eliminate opioids already intra-operatively towards a balanced, opioid-free approach (opioid-free anesthesia - OFA). In OFA drugs and techniques historically proven for their efficacy are combined in rational and defined protocols. They include ketamine, alpha-2 agonists, lidocaine, magnesium, anti-inflammatory drugs and regional anesthesia. Promising results have been obtained on perioperative outcome. For sure, analgesia is not reduced with OFA, but it is effective and with less opioid-related side effects. These benefits may be of particular importance in some high-risk patients, like OSAS, obese and chronic opioid-users/abusers. OFA may also increase patient-reported outcomes; despite it is difficult to specifically rule out the effect of intraoperative opioids. Finally, few data are available on long-term outcomes (persistent pain and opioid abuse, cancer outcome). New studies and data are required to elaborate the optimal approach for each patient/ surgery, but interest and publication are increasing and may open the road to the wider adoption of OFA.

An error in the reporting of one affiliation. Alberto Mantovani’s is affiliated with 4. Humanitas Clinical and Research Center – IRCCS, Milan, Italy instead of 1. Postgraduate School of Respiratory Medicine, University of Milan as stated in the initial publication.

In COVID-19, acute respiratory distress syndrome (ARDS) and thrombotic events are frequent, life-threatening complications. Autopsies commonly show arterial thrombosis and severe endothelial damage. Endothelial damage, which can play an early and central pathogenic role in ARDS and thrombosis, activates the lectin pathway of complement. Mannan-binding lectin-associated serine protease-2 (MASP-2), the lectin pathway's effector enzyme, binds the nucleocapsid protein of severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2), resulting in complement activation and lung injury. Narsoplimab, a fully human immunoglobulin gamma 4 (IgG4) monoclonal antibody against MASP-2, inhibits lectin pathway activation and has anticoagulant effects. In this study, the first time a lectin-pathway inhibitor was used to treat COVID-19, six COVID-19 patients with ARDS requiring continuous positive airway pressure (CPAP) or intubation received narsoplimab under compassionate use. At baseline and during treatment, circulating endothelial cell (CEC) counts and serum levels of interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed. Narsoplimab treatment was associated with rapid and sustained reduction of CEC and concurrent reduction of serum IL-6, IL-8, CRP and LDH. Narsoplimab was well tolerated; no adverse drug reactions were reported. Two control groups were used for retrospective comparison, both showing significantly higher mortality than the narsoplimab-treated group. All narsoplimab-treated patients recovered and survived. Narsoplimab may be an effective treatment for COVID-19 by reducing COVID-19-related endothelial cell damage and the resultant inflammation and thrombotic risk.

Aims: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. Methods and results: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with ‘typical’ acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7–4.5) vs. 2.4 (2.1–2.8) L/min/m2, P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = −0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1–2.5) vs. 1.6 (0.9–2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = −0.46, P = 0.038). Conclusions: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high c

Pain activates a general hormonal and inflammatory reaction is a main determinant in postsurgical patient’s recovery that may negatively affect the CV system, especially in high-risk patients. Pain can also become chronic, increasing the risk for CV dysfunctions. Epidural analgesia has various beneficial effects on patient’s outcome, including the reduction of stress response and sympathetic activation after surgery. Some data suggest a protective role of EA on CV morbidity, especially on ischemia and dysrhythmias. However, serious CV complications may be expected with neuraxial anesthesia. Traditional CV drugs such as alpha-2 agonists and beta-blockers display important role in pain treatment. Clonidine may also protect from CV morbidity perioperatively, by improving hemodynamic and sympathetic stabilities and reducing stress response, while beta-blockers display beneficial effects in cardiac surgery but may be deleterious in noncardiac surgery. On the other hand, common drugs that are effective for analgesia may also improve the risk for CV morbidity. COX-2 inhibitors are contraindicated for chronic use in pain patients; however, they may not be unsafe in the perioperative setting. Available data are sparse to conclude that short-time administration of COX-2 inhibitors in the perioperative setting is associated to higher risk of CV morbidity, except for patients at higher risk for cardiac events. As well, new data suggest that acetaminophen, which is traditionally considered safe in terms of CV risk, may not be as safe as believed. Opioids are safe, but can harm CV homeostasis in specific cases or when associated with other drugs; neuraxial opioids may protect from hemodynamic impairment and positively affect analgesia. Protecting heart function during pain flares means acting on nociceptive stimulus and on the organic response to pain; the concept should be to stabilize and bring homeostasis to a pain patient’s CV system, always balancing beneficial and detriment

A 21-year-old patient has been treated in emergency with venovenous extracorporeal membrane oxygenation after severe thoracic trauma causing severe air leak and haemothorax. The extracorporeal assistance was managed without heparin for 10 days till the full recovery of the lung, and no side-effect was recorded.

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare autosomal recessive disorder of neurotransmitter synthesis with lack of sympathetic autoregulation. Owing to hemodynamic regulatory dysfunction and impairment of sympathetic regulation of heart rate, anesthesia is challenging. We report the successful management of anesthesia in a 26-year-old pregnant woman presenting with a mild phenotype of AADCD. Neuraxial anesthesia was administered, as she had not developed complications previously. Thus, neuraxial anesthesia can also be used safely for a cesarean delivery with appropriate anticipation of potential autonomic disturbances and lack of adrenergic neurotransmission.

We aimed to characterize the epidemiology, diagnostic peculiarities and outcome determinants of bacterial myocarditis. Two cases from our institution and literature reports were collected ending up with a total of 66 cases. In 37 (56%) patients, the diagnosis was confirmed by magnetic resonance and histopathological criteria. The other patients were classified as having possible myocarditis. Only occurrence of rhythm disturbances was associated with the specific diagnosis of myocarditis (p = 0.04). Thirty-two (48%) patients presented with severe sepsis that was associated with a worse prognosis. At multivariate analysis, left ventricular ejection fraction (LVEF) at admission and heart rhythm disturbances were associated with incomplete recovery (odds ratio (OR) 1.1, 95% (CI) 1.03–1.2, p = 0.004 and OR 6.6, 95% CI 1.35–32.5, p = 0.02, respectively). In summary, bacterial myocarditis is uncommon. Most commonly, it is secondary to septic dissemination of bacteria or to transient secondary myocardial toxicity.

A referral hospital in the hardest-hit region of Italy had to manage a continuously increasing number of daily admissions for Covid-19 after delayed responses in the province allowed for rapid spread of the virus. Nineteen physicians in the province died.

Background: Novel Coronavirus SARS-CoV-2 pandemic is spreading around the world. At the end of February, the outburst of the pandemic has hit hard on northern Italian's hospitals. As of today, no data have been published regarding the severity of respiratory failure of patients presenting to the Emergency Departments. Moreover, the outcome the patients forced to undergo Continuous Positive Airway Pressure (CPAP) or Non-Invasive Positive Pressure Ventilation (NIPPV) due to lack of Intensive Care resources is unknown. “Papa Giovanni XXIII” hospital (HPG23) of Bergamo is one of the largest hospitals in the Country, with an Emergency Department (ED) managing over 100,000 patients per year. Methods: This is a retrospective observational study based on chart review of patients presenting to the Emergency Department of HPG23 from 29/02/2020 to 10/03/2020 with a clinical condition highly suspicious for COVID-19 infection. Registration of admission rates, severity of respiratory failure (ARDS classification), need of respiratory support, SARS-CoV-2 PCR test and outcome of patients treated with a ventilatory support were registered on 10th of May 2020. Findings: From 29/02 to 10/03 611 patients with a suspected diagnosis of COVID-19 infection were evaluated in our ED; 320 (52%) met the criteria for hospital admission and 99 (31%) needed to be immediately started on ventilatory support (81% CPAP, 7% NIPPV, 12% Invasive Mechanical Ventilation). Eighty-five (86%) of the 99 patients needing a ventilatory support eventually had SARS-CoV-2 infection confirmed by PCR test on nasal-pharyngeal swab. Their median PO2/FiO2 ratio was 128 (IQR 85–168), with 23 patients (29.5%) classified as severe ARDS. Mortality rate as of 10th of May was 76.5%, ranging from 44.4% within patients <60 years old to 85% within those older than 60 years (p = 0.001). NIPPV/CPAP failure occurred in 91.5% of patients. Interpretation: The population of patients suspected for COVID-19 infection presenting at o

Importance: Data on the association of COVID-19 vaccination with intensive care unit (ICU) admission and outcomes of patients with SARS-CoV-2-related pneumonia are scarce. Objective: To evaluate whether COVID-19 vaccination is associated with preventing ICU admission for COVID-19 pneumonia and to compare baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU. Design, Setting, and Participants: This retrospective cohort study on regional data sets reports: (1) daily number of administered vaccines and (2) data of all consecutive patients admitted to an ICU in Lombardy, Italy, from August 1 to December 15, 2021 (Delta variant predominant). Vaccinated patients received either mRNA vaccines (BNT162b2 or mRNA-1273) or adenoviral vector vaccines (ChAdOx1-S or Ad26.COV2). Incident rate ratios (IRRs) were computed from August 1, 2021, to January 31, 2022; ICU and baseline characteristics and outcomes of vaccinated and unvaccinated patients admitted to an ICU were analyzed from August 1 to December 15, 2021. Exposures: COVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine). Main Outcomes and Measures: The incidence IRR of ICU admission was evaluated, comparing vaccinated people with unvaccinated, adjusted for age and sex. The baseline characteristics at ICU admission of vaccinated and unvaccinated patients were investigated. The association between vaccination status at ICU admission and mortality at ICU and hospital discharge were also studied, adjusting for possible confounders. Results: Among the 10107674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5154914 (51.0%) were female. Of the 7863417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4010343 [51.4%] female), 6251417 (79.5%) received an mRNA vaccine, 550439 (7.0%) received an adenoviral vector vaccine, and 1061561 (13.5%) received a mix of vaccines and 4497875 (57.2

BACKGROUND: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS: Overall 28-day mortality in 1316 patients was 26.9%. Patients who did not report dyspnea at admission (N469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, P=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (P=0.21). CONCLUSIONS: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

Objectives:The effect of renin-angiotensin system inhibitors (RASIs) on mortality in patients with coronavirus disease (Covid-19) is debated. From a cohort of 1352 consecutive patients admitted with Covid-19 to Papa Giovanni XXIII Hospital in Bergamo, Italy, between February and April 2020, we selected and studied hypertensive patients to assess whether antecedent (prior to hospitalization) use of RASIs might affect mortality from Covid-19 according to age.Methods and results:Arterial hypertension was present in 688 patients. Overall mortality (in-hospital or shortly after discharge) was 35% (N = 240). After adjusting for 26 medical history variables via propensity score matching, antecedent use of RASIs (N = 459, 67%) was associated with a lower mortality in older hypertensive patients (age above the median of 68 years in the whole series), whereas no evidence of a significant effect was found in the younger group of the same population (P interaction = 0.001). In an analysis of the subgroup of 432 hypertensive patients older than 68 years, we considered two RASI drug subclasses, angiotensin-converting enzyme inhibitors (ACEIs, N = 156) and angiotensin receptor blockers (ARBs, N = 140), and assessed their respective effects by taking no-antecedent-use of RASIs as reference. This analysis showed that both antecedent use of ACEIs and antecedent use of ARBs were associated with a lower Covid-19 mortality (odds ratioACEI = 0.57, 95% confidence interval 0.36 - 0.91, P = 0.018) (odds ratioARB = 0.49, 95% confidence interval 0.29 - 0.82, P = 0.006).Conclusion:In the population of over-68 hypertensive Covid-19 patients, antecedent use of ACEIs or ARBs was associated with a lower all-cause mortality, whether in-hospital or shortly after discharge, compared with no-antecedent-use of RASIs.

Pulmonary Tumor Thrombotic Microangiopathy (PTTM) is a rare condition associated with neoplastic disorders, predominantly gastric cancer, leading to pre-capillary Pulmonary Hypertension (PH). The pathologic mechanism involved is a fibrocellular intimal proliferation of small pulmonary vessels sustained by nests of carcinomatous cells lodged in pulmonary vasculature. Clinical presentation is nonspecific, including progressive dyspnea and dry cough. Diagnosis of PTTM is extremely challenging ante-mortem and prognosis is poor. Here we describe the case of a middle-aged man, without known previous cancer history. The clinical course was rapidly unfavorable, with progressive dyspnea and PH associated with hemodynamic instability, eventually culminating in patient's death. PTTM diagnosis was made post-mortem. PTTM should be considered in any patient presenting with unexplained PH, especially if it is rapidly progressive, poorly responsive to standard approaches or there is suspected history of malignancy. A prompt diagnosis of PTTM could help in bringing light into this still under-recognized condition.

Heart failure (HF) is a pandemic syndrome characterised by raised morbidity and mortality. An acute HF event requiring hospitalisation is associated with a poor prognosis, in both the short and the long term. Moreover, early rehospitalisation after discharge negatively affects HF management and survival rates. Cardiovascular and non-cardiovascular conditions combine to increase rates of HF hospital readmission at 30 days. A tailored approach for HF pharmacotherapy while the patient is in hospital and immediately after discharge could be useful in reducing early adverse events that cause rehospitalisation and, consequently, prevent worsening HF and readmission during the vulnerable phase after discharge.

BACKGROUND: Gynecological procedures are among the most frequent surgical interventions, and effective postoperative analgesia is associated with improved patient comfort. Despite the efficacy of neuraxial analgesia, limitations and potential complications have led to seek new strategies for pain relief. A novel, pre-programmed, non-invasive, hand-held system (Sufentanil Sublingual Tablet System [SSTS]) displayed good results in the orthopedic setting. However, it has never been applied in gynecological procedures. METHODS: This retrospective observational case series evaluates receiving SSTS for postoperative analgesia. Data from 42 consecutive patients undergoing open gynecological surgery with Pfannenstiel incision were retrieved from medical charts in two Italian hospitals. RESULTS: The mean age was 49±11 years, and mean BMI was 24.4±4.6 kg/m2. We reported effective relief on both static and dynamic pain all along the perioperative period, with good effect on patient’s rehabilitation. Postoperative nausea and vomiting is the most common adverse effect, but the incidence was strongly decreased with medical prophylaxis. SSTS was easy to prepare, use and manage by both patients and care providers. CONCLUSIONS: SSTS may be an interesting option for postoperative analgesia in gynecologic procedures. The efficacy in the management of dynamic pain is an interesting outcome that needs to be compared with the other standards of pain management, such as neuraxial techniques. Rigorous studies are required to give conclusive evidence, but this is the first report, to our knowledge, of SSTS use in open gynecologic procedures. Our preliminary experience encourages the routine application of SSTS in gynecologic surgery and will help designing future randomized controlled trials on the topic.

Background: Prognostic factors affecting outcome of traumatic brain injury (TBI), despite their importance, are still under discussion. The purpose of this study was to describe risk factors of in-hospital mortality and outcome at 1 year in a homogeneously treated population of patients with moderate/severe TBI. Methods: A total of 193 consecutive patients with moderate or severe TBI (Glasgow Coma Scale [GCS] score 13–3, including patients with initial GCS score of 13 at high risk for subsequent neurologic deterioration), admitted to the intensive care unit, were retrospectively analyzed. In-hospital mortality and unfavorable outcome at 1 year, based on a Glasgow Outcome Scale–Extended score ≤4, were considered as primary and secondary outcomes. Results: At 1 year, unfavorable outcome occurred in 47.2%, including an in-hospital mortality of 19.7%. Increasing age, GCS motor score <3, coagulation disorders, and intracranial hypertension were acute risk factors of in-hospital mortality. In the 155 remaining survivors, Oxford Handicap Scale (OHS), posttraumatic cerebral infarction, cerebrospinal fluid disturbances, and length of intensive care unit stay were associated with unfavorable outcome at 1 year, in univariate analysis. A cutoff OHS score ≥3 discriminated the probability of an unfavorable outcome (area under the curve, 0.87; P < 0.001; specificity, 74%; sensitivity, 84%). Combining the effect of acute and subacute variables in a multivariate analysis, increasing age and OHS score were independent predictors of outcome. Conclusions: The results of this retrospective study confirmed age as the main acute risk factor and identified OHS as new potential subacute predictor of unfavorable outcome in moderate and severe TBI.

Perioperative hemodynamic management, through monitoring and intervention on physiological parameters to improve cardiac output and oxygen delivery (goal-directed therapy, GDT), may improve outcome. However, an italian survey has revealed that hemodynamic protocols are applied by only 29.1% of anesthesiologists. aim of this paper is to provide clinical guidelines for a rationale use of perioperative hemodynamic management in non cardiac surgical adult patients, oriented for Italy and updated with most recent studies. Guidelines were elaborated according to NICE (National Institute for Health and Care Excellence) and GRADE system (Grading of Recommendations of Assessment Development and Evaluations). Key questions were formulated according to PICO system (Population, Intervention, Comparators, Outcome). Guidelines and systematic reviews were identified on main research databases and strategy was updated to June 2018. There is not enough good quality evidence to support the adoption of a GDT protocol in order to reduce mortality, although it may be useful in high risk patients. Perioperative GDT protocol to guide fluid therapy is recommended to reduce morbidity. continuous monitoring of arterial pressure may help to identify short periods of hemodynamic instability and hypotension. Fluid strategy should aim to a near zero balance in normovolemic patients at the beginning of surgery, and a slight positive fluid balance may be allowed to protect renal function. Drugs such as inotropes, vasocostrictors, and vasodilatator should be used only when fluids alone are not sufficient to optimize hemodynamics. Perioperative GDT protocols are associated with a reduction in costs, although no economic study has been performed in Italy.

Background Gender-related factors might affect vulnerability to Covid-19. The aim of this study was to describe the role of gender on clinical features and 28-day mortality in Covid-19 patients. Methods Observational study of Covid-19 patients hospitalized in Bergamo, Italy, during the first three weeks of the outbreak. Medical records, clinical, radiological and laboratory findings upon admission and treatment have been collected. Primary outcome was 28-day mortality since hospitalization. Results 431 consecutive adult patients were admitted. Female patients were 119 (27.6%) with a mean age of 67.0 +/- 14.5 years (vs 67.8 +/- 12.5 for males, p = 0.54). Previous history of myocardial infarction, vasculopathy and former smoking habits were more common for males. At the time of admission PaO2/FiO(2) was similar between men and women (228 [IQR, 134-273] vs 238 mmHg [150-281], p = 0.28). Continuous Positive Airway Pressure (CPAP) assistance was needed in the first 24 h more frequently in male patients (25.7% vs 13.0%; p = 0.006). Overall 28-day mortality was 26.1% in women and 38.1% in men (p = 0.018). Gender did not result an independent predictor of death once the parameters related to disease severity at presentation were included in the multivariable analysis (p = 0.898). Accordingly, the Kaplan-Meier survival analysis in female and male patients requiring CPAP or non-invasive ventilation in the first 24 h did not find a significant difference (p = 0.687). Conclusion Hospitalized women are less likely to die from Covid-19; however, once severe disease occurs, the risk of dying is similar to men. Further studies are needed to better investigate the role of gender in clinical course and outcome of Covid-19.

Rationale: Treatment with noninvasive ventilation (NIV) in coronavirus disease (COVID-19) is frequent. Shortage of intensive care unit (ICU) beds led clinicians to deliver NIV also outside ICUs. Data about the use of NIV in COVID-19 is limited. Objectives: To describe the prevalence and clinical characteristics of patientswith COVID-19 treated with NIVoutside the ICUs. To investigate the factors associated with NIV failure (need for intubation or death). Methods: In this prospective, single-day observational study, we enrolled adult patients with COVID-19 who were treated with NIV outside the ICU from 31 hospitals in Lombardy, Italy. Results: We collected data on demographic and clinical characteristics, ventilatorymanagement, and patient outcomes.Of 8,753 patients with COVID-19 present in the hospitals on the study day, 909 (10%) were receiving NIV outside the ICU. A majority of patients (778/909; 85%) patients were treated with continuous positive airway pressure (CPAP), which was delivered by helmet in 617 (68%) patients. NIV failed in 300 patients (37.6%), whereas 498 (62.4%) patients were discharged alive without intubation. Overall mortality was 25%. NIV failure occurred in 152/284 (53%) patients with an arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FIO2) ratio ,150 mm Hg. Higher C-reactive protein and lower PaO2/FIO2 and platelet counts were independently associated with increased risk of NIV failure. Conclusions: The use of NIV outside the ICUs was common in COVID-19, with a predominant use of helmet CPAP, with a rate of success.60% and close to 75% in full-treatment patients. C-reactive protein, PaO2/FIO2, and platelet counts were independently associated with increased risk of NIV failure.

Sacubitril with valsartan (sacubitril/valsartan) is a relatively novel compound that has become a milestone in the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (HFrEF) in the last decade. Contemporary data suggest that sacubitril/valsartan is associated with improved outcomes compared with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and has a greater beneficial effect on myocardial reverse remodelling. Additionally, two recent trials have shown that sacubitril/valsartan is well-tolerated even in the acute HF setting, thus enabling a continuum of use in the patient’s journey with HFrEF. This article summarises available data on the effectiveness and tolerability of sacubitril/valsartan in patients with HFrEF, and provides the clinician with practical insights to facilitate the use of this drug in every setting, with an emphasis on acute HF, hypotension, electrolyte imbalance and renal insufficiency

Generalized arterial calcification of infancy (GACI), or idiopathic infantile arterial calcification, is a rare autosomal-recessive disease recognized aAs an inherited disorder characterized by severe pathologic calcification of large- and medium-sized arteries accompanied by smooth muscle cell (SMC) hyperplasia leading to vascular obstruction [1]. The prognosis is extremely poor, with 85% of affected infants dying within the first 6 months of life. Loss-of-function mutations in the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene is recognized as the main defect associated with GACI [1]. The underlying pathogenesis of osteogenic transition leading to calcification and severe stenosis in GACI, however, is poorly understood. Herein, we present a case of a GACI patient with cardiac complications who exhibited extensive vascular disease at autopsy.

Over the past 2 decades, a large number of guidelines for aneurysmal subarachnoid hemorrhage (aSAH) management have been proposed. The primary aim of these "evidence-based" guidelines is to improve the care of aSAH patients by summarizing and making current knowledge readily available to clinicians. However, an investigation into aSAH guidelines, their changes along time and their successful translation into clinical practice is still lacking. We performed a literature search of historical events and subarachnoid hemorrhage guidelines using the Entrez PubMed NIH, Embase, and Cochrane databases for articles published up to November of 2016. Data were summarized for guidelines on aSAH management and cross-sectional studies of their application. A total of 11 guidelines and 10 cross-sectional studies on aSAH management were analyzed. The use of nimodipine for the treatment of SAH is the only recommendation that remained consistent across guidelines over time (r=0.82; P<0.05). A shift in the definitive treatment for aneurysms from open surgical clipping to endovascular coiling was also noted (r=-0.91; r=0.96; P<0.005). In addition, definitive treatment for aneurysm is being performed earlier. The use of triple-H therapy and the long-Term administration of anticonvulsive therapy has decreased. Finally, written protocols for aSAH management were not consistently used across tertiary care institutions (r=-0.46; P=0.43; confidence interval,-0.95 to-0.70). We conclude that guidelines related to the management of patients with SAH have evolved from a consensus-based approach into an evidence-based approach. Nevertheless, the translation into clinical practice is limited, suggesting that personalized approaches to care is inherent, and perhaps necessary for aSAH management.

Objective: There is increasing burnout incidence among medical disciplines, and physicians working in emergency settings seem at higher risk. Cardiac anesthesiology is a stressful anesthesiology subspecialty dealing with high-risk patients. The authors hypothesized a high risk of burnout in cardiac anesthesiologists. Design: National survey conducted on burnout. Setting: Italian cardiac centers. Participants: Cardiac anesthesiologists. Interventions: The authors administered via email an anonymous questionnaire divided into 3 parts. The first 2 parts evaluated workload and private life. The third part consisted of the Maslach Burnout Inventory test with its 3 constituents: high emotional exhaustion, high depersonalization, and low personal accomplishment. Measurements and Main Results: The authors measured the prevalence and risk of burnout through the Maslach Burnout Inventory questionnaire and analyzed factors influencing burnout. Among 670 contacts from 71 centers, 382 cardiac anesthesiologists completed the survey (57%). The authors found the following mean Maslach Burnout Inventory values: 14.5 ± 9.7 (emotional exhaustion), 9.1 ± 7.1 (depersonalization), and 33.7 ± 8.9 (personal accomplishment). A rate of 34%, 54%, and 66% of respondents scored in “high” or “moderate-high” risk of burnout (emotional exhaustion, depersonalization, and personal accomplishment, respectively). The authors found that, if offered to change subspecialty, 76% of respondents would prefer to remain in cardiac anesthesiology. This preference and parenthood were the only 2 investigated factors with a protective effect against all components of burnout. Significantly lower burnout scores were found in more experienced anesthesiologists. Conclusion: A relatively high incidence of burnout was found in cardiac anesthesiologists, especially regarding high depersonalization and low personal accomplishment. Nonetheless, most of the respondents would choose to remain in cardiac anesthesiology.

In amyotrophic lateral sclerosis (ALS), respiratory muscle weakness leads to respiratory failure and death. Non-invasive positive pressure ventilation (NIPPV) appears to reduce lung function decline, thus improving survival and quality-of-life of patients affected by the disease. Unfortunately, clinical features and timing to start NIPPV are not well defined. Starting from recent findings, we examine established and novel tests of respiratory muscle function that could help clinicians decide whether and when to start NIPPV in ALS. Non-invasive tests estimate the function of inspiratory, expiratory, and bulbar muscles, whereas clinical examination allows to assess the overall neurologic and respiratory symptoms and general conditions. Most of the studies recommend that together with a thorough clinical evaluation of the patient according to current guidelines, vital capacity, maximal static and sniff nasal inspiratory pressures, maximal static expiratory pressures and peak cough expiratory flow, and nocturnal pulse oximetry be measured. A sound understanding of physiology can guide the physician also through the current armamentarium for additional supportive treatments for ALS, such as symptomatic drugs and new treatments to manage sialorrhea and thickened saliva, cough assistance, air stacking, and physiotherapy. In conclusion, careful clinical and functional evaluation of respiratory function and patient's preference are key determinants to decide "when" and "to whom" respiratory treatments can be provided.

PURPOSE OF REVIEW: Anesthesiologists and intensivists may be involved in the management of aneurysmal subarachnoid hemorrhage (aSAH) patients at various stages of care. This article will review the recent advances in the periprocedural management of aSAH patients. RECENT FINDINGS: New scoring systems to assess gravity and prognosis of aSAH patients have been evaluated and proposed. Rebleeding still remains, with early aneurysmal treatment, a major challenge in the first hours of aSAH management. In the last decades, the treatment of the aSAH has shifted from clipping to coiling and more recently, the use of flow diversion technique has been introduced in selected patients. Although these improvements allow treatment of more complex aneurysms, they have implications for the anesthesiologist, including requiring the management of anticoagulation with its inherent risks. Even though knowledge, monitoring, and management of postprocedural phase of aSAH patients has improved, vasospasm and cerebral-delayed ischemia still remain the major and devastating complications in the postoperative course of aSAH patients. SUMMARY: Despite recent progress in the scoring, diagnosis, and treatment of aSAH patients, the periprocedural management of these patients is still a major challenge for anesthesiologists and intensivists, who are involved from the first phase of the aneurysm rupture through the postoperative phases and vasospasm period.

In hip surgery, regional anesthesia offers benefits in pain management and recovery. There are a wide range of regional analgesic options; none have shown to be superior. Lumbar plexus block, femoral nerve block, and fascia iliaca block are the most supported by published literature. Other techniques, such as selective obturator and/or lateral femoral cutaneous nerve blocks, represent alternatives. Newer approaches, such as quadratus lumborum block and local infiltration analgesia, require rigorous studies. To realize long-term outcome benefits, postoperative regional analgesia must be tailored to the individual patient and last longer.

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.

Question What are the baseline characteristics and outcomes of patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection admitted to intensive care units (ICUs) in Lombardy, Italy? Findings In this retrospective case series that involved 1591 critically ill patients admitted from February 20 to March 18, 2020, 99% (1287 of 1300 patients) required respiratory support, including endotracheal intubation in 88% and noninvasive ventilation in 11%; ICU mortality was 26%. Meaning In this case series of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed coronavirus disease 2019 (COVID-19), a high proportion required mechanical ventilation and ICU mortality was 26% as of March 25, 2020.Importance In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center

Importance: Many patients with coronavirus disease 2019 (COVID-19) are critically ill and require care in the intensive care unit (ICU). Objective: To evaluate the independent risk factors associated with mortality of patients with COVID-19 requiring treatment in ICUs in the Lombardy region of Italy. Design, setting, and participants: This retrospective, observational cohort study included 3988 consecutive critically ill patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinating center (Fondazione IRCCS [Istituto di Ricovero e Cura a Carattere Scientifico] Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network from February 20 to April 22, 2020. Infection with severe acute respiratory syndrome coronavirus 2 was confirmed by real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swabs. Follow-up was completed on May 30, 2020. Exposures: Baseline characteristics, comorbidities, long-term medications, and ventilatory support at ICU admission. Main outcomes and measures: Time to death in days from ICU admission to hospital discharge. The independent risk factors associated with mortality were evaluated with a multivariable Cox proportional hazards regression. Results: Of the 3988 patients included in this cohort study, the median age was 63 (interquartile range [IQR] 56-69) years; 3188 (79.9%; 95% CI, 78.7%-81.1%) were men, and 1998 of 3300 (60.5%; 95% CI, 58.9%-62.2%) had at least 1 comorbidity. At ICU admission, 2929 patients (87.3%; 95% CI, 86.1%-88.4%) required invasive mechanical ventilation (IMV). The median follow-up was 44 (95% CI, 40-47; IQR, 11-69; range, 0-100) days; median time from symptoms onset to ICU admission was 10 (95% CI, 9-10; IQR, 6-14) days; median length of ICU stay was 12 (95% CI, 12-13; IQR, 6-21) days; and median length of IMV was 10 (95% CI, 10-11; IQR, 6-17) days. Cumulative observation time was 164 305 patient-days. Hospital and ICU mortality ra

Background: Previous studies have shown beneficial effects of levosimendan in high-risk patients undergoing cardiac surgery. Two large randomized controlled trials (RCTs), however, showed no advantages of levosimendan. Methods: We performed a systematic review and meta-analysis (MEDLINE and Embase from inception until March 30, 2017), investigating whether levosimendan offers advantages compared with placebo in high-risk cardiac surgery patients, as defined by preoperative left ventricular ejection fraction (LVEF) ≤ 35% and/or low cardiac output syndrome (LCOS). The primary outcomes were mortality at longest follow-up and need for postoperative renal replacement therapy (RRT). Secondary postoperative outcomes investigated included myocardial injury, supraventricular arrhythmias, development of LCOS, acute kidney injury (AKI), duration of mechanical ventilation, intensive care unit and hospital lengths of stay, and incidence of hypotension during drug infusion. Results: Six RCTs were included in the meta-analysis, five of which investigated only patients with LVEF ≤ 35% and one of which included predominantly patients with LCOS. Mortality was similar overall (OR 0.64 [0.37, 1.11], p = 0.11) but lower in the subgroup with LVEF < 35% (OR 0.51 [0.32, 0.82], p = 0.005). Need for RRT was reduced by levosimendan both overall (OR 0.63 [0.42, 0.94], p = 0.02) and in patients with LVEF < 35% (OR 0.55 [0.31, 0.97], p = 0.04). Among secondary outcomes, we found lower postoperative LCOS in patients with LVEF < 35% receiving levosimendan (OR 0.49 [0.27, 0.89], p = 0.02), lower overall AKI (OR 0.62 [0.42, 0.92], p = 0.02), and a trend toward lower mechanical support, both overall (p = 0.07) and in patients with LVEF < 35% (p = 0.05). Conclusions: Levosimendan reduces mortality in patients with preoperative severely reduced LVEF but does not affect overall mortality. Levosimendan reduces the need for RRT after high-risk cardiac surgery.

The autonomic nervous system, the renin–angiotensin–aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II. We review the multiple, potentially competing, substrates for neprilysin inhibition, and the resultant composite clinical effects of ARNi therapy. A mechanistic understanding of this novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.