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Cerebrovascular disease (CVD) can encompass a wide variety of medical acute events, such as ischemic or hemorrhagic stroke, to insidious pathological processes, such as atherosclerotic changes and small-vessel diseases. This chapter focuses on the management of acute ischemic and hemorrhagic stroke, including subarachnoid hemorrhage and venous sinus thrombosis. Stroke is the most common manifestation of CVD disease among adults. It is typically characterized as a neurological deficit attributed to an acute focal injury of the central nervous system by a vascular cause, including cerebral infarction. Common stroke signs and symptoms may include sudden onset of weakness, hemiparesis, monoparesis, or rarely quadriparesis, hemisensory deficits, visual loss or visual field deficits, diplopia, dysarthria, altered speech, aphasia, facial droop, ataxia, vertigo, nystagmus, and sudden decrease in the level of consciousness. The surgical approach to patients with stroke emergencies in some contexts can greatly reduce the unfavorable outcome and mortality.

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.

Adverse drug reactions affecting the skin have particular relevance as they may cause significant mortality and a possible modification of the benefit/risk profile of the concerned drug. The following entities are of special importance: Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug rash with eosinophilia and systemic symptoms (DRESS). On the above mentioned reactions we focused our surveillance programme in the Lombardy region, the REACT-Lombardia project. The REACT registry involved 22 hospital-based dermatological centres, collecting, from April 2009 up to March 2014, a total of 72 cases of SJS-TEN, 17 cases of AGEP and 9 cases of DRESS. Allopurinol was the drug associated with the largest number of cases of SJS/TEN (21 cases) followed by paracetamol (8 cases), levofloxacine (6 cases) and carbamazepine (4 cases). The risk for specific drug exposures was estimated by employing drug utilization data expressed as Defined Daily Doses (DDD). Mortality rate from SJS-TEN was 21%. Together with the registry, a "hub and spoke" clinical network for the management of severe cutaneous reactions was established with the Burn Unit of Niguarda Ca' Granda Hospital as the reference center for the most critical patients.

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

Fifty patients undergoing cardiac surgery suffering from coronary artery disease and valvular incompetence or stenosis, were randomly divided into two groups of 25 patients to compare the plasmapheresis effects on bleeding, transfusion requirements, economicity and paramedical staff compliance versus intraoperative autotransfusion. Standardized anesthetics, perfusion, and surgical techniques were used. We used plasmapheresis with cell saver and haemodilution with bypass ultrafiltration. Platelet counts, haemoglobin concentration, haematocrit, fibrinogen, bleeding times were evaluated at fixed times for the patients on plasmapheresis and after surgical homologous transfusion. It was that these parameters did not change significantly in the two groups. Intraoperative plasmapheresis is more expensive and less accepted into an operating room than autotransfusion. Intraoperative plasmapheresis will be a good alternative to haemodilution for selected patients.

Streptococcus pyogenes is a rare but aggressive cause of meningitis, which often evolves in a poor outcome with fatal consequences. Although lumbar puncture and CT scan of the brain are the gold standard of diagnosis of cerebral infections, they can have some limitations. We report and describe the clinical history and neuroimaging of a 36-year-old woman admitted to the emergency department of our hospital three days after the onset of earache and otorrhoea. When the patient developed an emergent refractory status epilepticus, the CT scan of the brain showed an unusual pneumocephalus. However, the MRI study of the brain revealed a pachymeningitis with partial thrombosis of the right transverse sinus and subdural empyema due to a S. pyogenes otitis media. Prompt diagnosis and the specific findings of the MRI allowed rapid correct treatment and thus led to a good outcome for the patient.

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called ‘COVID-19 associated coagulopathy’ (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined.

ImportanceData 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresCOVID-19 vaccination status (no vaccination, mRNA vaccine, adenoviral vector vaccine).Main Outcomes and MeasuresThe 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.ResultsAmong the 10 107 674 inhabitants of Lombardy, Italy, at the time of this study, the median [IQR] age was 48 [28-64] years and 5 154 914 (51.0%) were female. Of the 7 863 417 individuals who were vaccinated (median [IQR] age: 53 [33-68] years; 4 010 343 [51.4%] female), 6 251 417 (79.5%) received an mRNA vaccine, 550 439 (7.0%) received an adenoviral vector vaccine, and 1 061 561 (13.5%) received a mix of vaccines and 4 497 875 (57.2%) were boosted. Compared with unvaccinated people, IRR of individuals who received an mRNA vaccine within 120 days from the last dose was 0.03 (95% CI, 0.03-0.04; P P P P P o2) and fraction of inspiratory oxygen (FiO2) at ICU admission (median [IQR]: 138 [100-180] vs 120 [90-158] mm Hg; P = .007). Factors associated with ICU and hospital mortality were higher age, premorbid heart disease, lower Pao2/FiO2 at ICU admission, and female sex (this factor only for ICU mortality). ICU and hospital mortality were similar between vaccinated and unvaccinated patients.Conclusions and RelevanceIn this cohort study, mRNA and adenoviral vector vaccines were associated with significantly lower risk of ICU admission for COVID-19 pneumonia. ICU and hospital mortality were not associated with vaccinated status. These findings suggest a substantial reduction of the risk of developing COVID-19–related severe acute respiratory failure requiring ICU admission among vaccinated people.

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.

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.

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.

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.

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.

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, Vicious circle between the lung and the heart in COVID‐19. Coronavirus‐2 causes an interstitial pneumonia characterized by low lung compliance. The ventilation/perfusion mismatch of non‐ventilated but perfused lung zones is enhanced by specific virus‐related mechanisms, with blunted hypoxic pulmonary vasoconstriction and normal PVR, further promoting the intrapulmonary shunt. High cardiac output due to acute inflammation and hypoxaemia, with low PVR and unimpeded left ventricular preload, predisposes to high filling pressure, which might be favoured by patient characteristics (elderly with cardiovascular comorbidities) and further exacerbated by virus‐related cardiac remodelling. High left ventricular filling pressure promotes lung congestion with further reduction of lung compliance. ACE, angiotensin‐converting enzyme; CSTAT, static lung compliance; LV, left ventricle; PAWP, pulmonary artery wedge pressure; PVR, pulmonary vascular resistance; Qs/Qt, intrapulmonary shunt; SIRS, systemic inflammatory response syndrome.

Highlights • Narsoplimab down-modulates SARS-CoV-2-induced activation of the lectin pathway and endothelial cell damage, reducing thrombotic risk. • All patients treated with narsoplimab, a lectin-pathway inhibitor, improved and survived without any drug-related adverse events., 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.

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/FiO2 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.

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

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.

The control of post-operative pain in Italy and other western countries is still suboptimal. In recent years, the Sufentanil Sublingual Tablet System (SSTS; Zalviso; AcelRx Pharmaceuticals, Redwood City, CA, USA), which is designed for patient-controlled analgesia (PCA), has entered clinical practice. SSTS enables patients to manage moderate-to-severe acute pain during the first 72 postoperative hours directly in the hospital setting. However, the role of SSTS within the current framework of options for the management of post-operative pain needs to be better established. This paper presents the position on the use of SSTS of a multidisciplinary group of Italian Experts and provides protocols for the use of this device.

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.

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 detrimental effects of any treatment.

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.

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.

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.

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

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 rates were 12 (95% CI, 11-12) and 27 (95% CI, 26-29) per 1000 patients-days, respectively. In the subgroup of the first 1715 patients, as of May 30, 2020, 865 (50.4%) had been discharged from the ICU, 836 (48.7%) had died in the ICU, and 14 (0.8%) were still in the ICU; overall, 915 patients (53.4%) died in the hospital. Independent risk factors associated with mortality included older age (hazard ratio [HR], 1.75; 95% CI, 1.60-1.92), male sex (HR, 1.57; 95% CI, 1.31-1.88), high fraction of inspired oxygen (Fio2) (HR, 1.14; 95% CI, 1.10-1.19), high positive end-expiratory pressure (HR, 1.04; 95% CI, 1.01-1.06) or low Pao2:Fio2ratio (HR, 0.80; 95% CI, 0.74-0.87) on ICU admission, and history of chronic obstructive pulmonary disease (HR, 1.68; 95% CI, 1.28-2.19), hypercholesterolemia (HR, 1.25; 95% CI, 1.02-1.52), and type 2 diabetes (HR, 1.18; 95% CI, 1.01-1.39). No medication was independently associated with mortality (angiotensin-converting enzyme inhibitors HR, 1.17; 95% CI, 0.97-1.42; angiotensin receptor blockers HR, 1.05; 95% CI, 0.85-1.29). Conclusions and Relevance In this retrospective cohort study of critically ill patients admitted to ICUs in Lombardy, Italy, with laboratory-confirmed COVID-19, most patients required IMV. The mortality rate and absolute mortality were high.

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.