First imported case of Candida auris infection in Milan, Italy: genomic characterisation.

PURPOSE: Candida auris, an emerging multidrug-resistant yeast, has been reported worldwide. In Italy, the first case was reported in 2019. We describe the first case of C. auris, imported from Greece, in Milan, using whole genome sequencing to characterise mutations associated with antifungal resistance. CASE PRESENTATION: On October 2022 an 80-year-old Italian man was hospitalised in Greece. In the absence of clinical improvement, the patient was transferred to our hospital, in Italy, where blood culture resulted positive for C. auris. Despite therapy, the patient died of septic shock. In a phylogenetic analysis the genome was assigned to Clade I with strains from Kenya, United Arab Emirates and India. D1/D2 region resulted identical to a Greek strain, as for many other strains from different World regions, highlighting the diffusion of this strain. CONCLUSION: Importation of C. auris from abroad has been previously described. We report the first case of C. auris imported into Italy from Greece, according to phylogenetic analysis. This case reinforces the need for monitoring critically ill hospitalised patients also for fungi and addresses the need for the standardisation of susceptibility testing and strategies for diagnosis and therapy.

Awake pronation with helmet CPAP in early COVID-19 ARDS patients: effects on respiratory effort and distribution of ventilation assessed by EIT.

Prone positioning with continuous positive airway pressure (CPAP) is widely used for respiratory support in awake patients with COVID-19-associated acute respiratory failure. We aimed to assess the respiratory mechanics and distribution of ventilation in COVID-19-associated ARDS treated by CPAP in awake prone position. We studied 16 awake COVID-19 patients with moderate-to-severe ARDS. The study protocol consisted of a randomized sequence of supine and prone position with imposed positive end-expiratory pressure (PEEP) of 5 and 10 cmH2O delivered by helmet CPAP. Respiratory mechanics and distribution of ventilation were assessed through esophageal pressure (PES) and electrical impedance tomography (EIT). At the end of each 20-min phase, arterial blood gas analysis was performed, and PES swing and EIT tracings were recorded for the calculation of the respiratory mechanics and regional ventilation. The patient's position had no significant effects on respiratory mechanics. EIT analysis did not detect differences among global indices of ventilation. A significant proportion of pixels in the sternal region of interest showed an increase in compliance from the supine to prone position and PaO2/FIO2 increased accordingly. The best improvement of both PaO2/FIO2 and sternal compliance was obtained in the prone position with PEEP 10 cmH2O. In the studied subjects, prone positioning during CPAP treatment raised oxygenation without improvement of "protective" ventilation or global ventilatory inhomogeneity indices. Prone positioning with higher PEEP significantly increased the compliance of sternal regions.

Impact of SARS-CoV-2 Omicron and Delta variants in patients requiring intensive care unit (ICU) admission for COVID-19, Northern Italy, December 2021 to January 2022.

This multicenter observational study included 171 COVID-19 adult patients hospitalized in the ICUs of nine hospitals in Lombardy (Northern Italy) from December, 1st 2021, to February, 9th 2022. During the study period, the Delta/Omicron variant ratio of cases decreased with a delay of two weeks in ICU patients compared to that in the community; a higher proportion of COVID-19 unvaccinated patients was infected by Delta than by Omicron whereas a higher rate of COVID-19 boosted patients was Omicron-infected. A higher number of comorbidities and a higher comorbidity score in ICU critically COVID-19 inpatients was positively associated with the Omicron infection as well in vaccinated individuals. Although people infected by Omicron have a lower risk of severe disease than those infected by Delta variant, the outcome, including the risk of ICU admission and the need for mechanical ventilation due to infection by Omicron versus Delta, remains uncertain. The continuous monitoring of the circulating SARS-CoV-2 variants remains a milestone to counteract this pandemic.

The efficacy of venous-arterial membrane oxygenation for emergency extracorporeal life support: results from a single-center large series over 6 years.

The efficacy of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in supporting cardio-pulmonary resuscitation for cardiac arrest is still debated. This study aimed to evaluate the outcome of patients treated with VA-ECMO positioned according to different clinical indications. The method is retrospective data analysis from patients admitted to a tertiary referral center for VA-ECMO in 6 years. The study population was divided into three groups based on the VA-ECMO indication: patients with refractory cardiac arrest (CA group), cardiogenic shock after return of spontaneous circulation (CS-ROSC group), and cardiogenic shock without cardiac arrest (CS group). Seventy-nine patients underwent emergency VA-ECMO, 49 patients (62.0%) were in the CA group, 14 (17.7%) in the CS-ROSC group, and 16 patients (20.3%) in the CS group. The overall survival at 28 days was different between the three groups (6.1% in the CA group, 64.2% in the CS-ROSC group, and 50.0% in the CS group, p < 0.001) and remained significant at 12 months (p < 0.001). Furthermore, the Cerebral Performance Category at 12 months differed between groups with good outcomes in 4.1% of patients in CA, 50.0% in CS-ROSC, and 31.2% in CS groups (p < 0.001). In the studied population, emergency VA-ECMO had negligible efficacy in refractory cardiac arrest, while it was correlated with a good outcome in cardiogenic shock after cardiac arrest, such as in cardiogenic shock alone. Patients with ROSC appear to benefit from VA-ECMO in the setting of persistent shock at rates comparable to cardiogenic shock patients who never sustained cardiac arrest.

Cardiorespiratory coupling in mechanically ventilated patients studied via synchrogram analysis.

Respiration and cardiac activity are strictly interconnected with reciprocal influences. They act as weakly coupled oscillators showing varying degrees of phase synchronization and their interactions are affected by mechanical ventilation. The study aims at differentiating the impact of three ventilatory modes on the cardiorespiratory phase coupling in critically ill patients. The coupling between respiration and heartbeat was studied through cardiorespiratory phase synchronization analysis carried out via synchrogram during pressure control ventilation (PCV), pressure support ventilation (PSV), and neurally adjusted ventilatory assist (NAVA) in critically ill patients. Twenty patients were studied under all the three ventilatory modes. Cardiorespiratory phase synchronization changed significantly across ventilatory modes. The highest synchronization degree was found during PCV session, while the lowest one with NAVA. The percentage of all epochs featuring synchronization regardless of the phase locking ratio was higher with PCV (median: 33.9%, first-third quartile: 21.3-39.3) than PSV (median: 15.7%; first-third quartile: 10.9-27.8) and NAVA (median: 3.7%; first-third quartile: 3.3-19.2). PCV induces a significant amount of cardiorespiratory phase synchronization in critically ill mechanically ventilated patients. Synchronization induced by patient-driven ventilatory modes was weaker, reaching the minimum with NAVA. Findings can be explained as a result of the more regular and powerful solicitation of the cardiorespiratory system induced by PCV. The degree of phase synchronization between cardiac and respiratory activities in mechanically ventilated humans depends on the ventilatory mode.

National Information Campaign Revealed Disease Characteristic and Burden in Adult Patients Suffering from Atopic Dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease often associated with a significant impairment in the quality of life of affected patients. The Italian Society of Dermatology and Venereology (SIDeMaST) planned a national information campaign, providing direct access to 27 dermatologic centers dedicated to the management of AD. The aim of this study aimed was to outline critical aspects related to AD in the general population. Overall, 643 adult subjects were included in this study, and in 44.2% (284/643) of cases, a diagnosis of AD was confirmed, whereas about 55% of subjects were affected by other pruritic cutaneous diseases. Higher intensity of pruritus and sleep disturbance, as well as an increased interference in sport, work, and social confidence was reported in the AD group compared to the non-AD group. In the AD subgroup, the mean duration of disease was of 15.3 years, with a mean eczema area and severity index (EASI) score of 11.2, and investigator global assessment (IGA) score of 1.9 and an itch numeric rating scale (NRS) of 6.9. Almost 32% of patients were untreated, either with topical or systemic agents, whereas 44.3% used routine topical compounds (topical corticosteroids and calcineurin inhibitors), and only 7.0% of patients were systemically treated. Only 2.8% of patients reported complete satisfaction with the treatment received for AD to date. This study reveals a profound unmet need in AD, showing a poorly managed and undertreated patient population despite a high reported burden of disease. This suggests the usefulness of information campaigns with the goal of improving patient awareness regarding AD and facilitating early diagnosis and access to dedicated healthcare institutions.

Tuscany consensus for the treatment of moderate-severe psoriasis: update and focus on practical guidelines for place in therapy of anti-IL-17 and anti-IL-23 biologics.

Psoriasis is a common chronic skin disease characterized by a worldwide distribution and a natural tendency towards progression. According to the many clinical forms, the extension of the disease and the many comorbidities, almost the 20% of the patients require a systemic treatment. Biologics have greatly changed the ongoing of psoriasis and the quality of life of psoriasis patients. After the anti-TNF-alpha, which were the first biologics in use for psoriasis, the improvement in knowledge of the pathogenetic mechanisms underlying the disease has led to the development of a series of more specific therapies for psoriasis. This "second generation" of biologics includes the interleukin (IL)-12/23 inhibitor ustekinumab, IL-17 inhibitors (secukinumab and ixekizumab), the IL-17 receptor A (IL-17RA) antagonist brodalumab, and the IL-23 inhibitors guselkumab, risankizumab and tildrakizumab. This study represents an update of the Tuscany consensus focused on the use of new drugs, such as anti-IL-17 and anti-IL-23 in moderate-to-severe psoriasis and their correct place in therapy according to specific clinical requests and in full respect of the current financial restrictions.

Effects of Prone Position on Lung Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study.

OBJECTIVES: Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19-associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT). DESIGN: Experimental, physiologic study. SETTING: Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU. PATIENTS: Twenty-one intubated patients with moderate or severe C-ARDS. INTERVENTIONS: First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position). MEASUREMENTS AND MAIN RESULTS: Prone position induced recruitment in the dorsal part of the lungs (12.5% ± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (-6.9% ± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ± 15 vs 45 ± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ± 0.16 vs 1.30 ± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3-23.4] vs 4.3 [0.7-6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching. CONCLUSIONS: Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.

Acute kidney injury (AKI) in patients with Covid-19 infection is associated with ventilatory management with elevated positive end-expiratory pressure (PEEP).

BACKGROUND: Acute kidney injury (AKI) in Covid-19 patients admitted to the intensive care unit (ICU) is common, and its severity may be associated with unfavorable outcomes. Severe Covid-19 fulfills the diagnostic criteria for acute respiratory distress syndrome (ARDS); however, it is unclear whether there is any relationship between ventilatory management and AKI development in Covid-19 ICU patients. PURPOSE: To describe the clinical course and outcomes of Covid-19 ICU patients, focusing on ventilatory management and factors associated with AKI development. METHODS: Single-center, retrospective observational study, which assessed AKI incidence in Covid-19 ICU patients divided by positive end expiratory pressure (PEEP) tertiles, with median levels of 9.6 (low), 12.0 (medium), and 14.7 cmH2O (high-PEEP). RESULTS: Overall mortality was 51.5%. AKI (KDIGO stage 2 or 3) occurred in 38% of 101 patients. Among the AKI patients, 19 (53%) required continuous renal replacement therapy (CRRT). In AKI patients, mortality was significantly higher versus non-AKI (81% vs. 33%, p < 0.0001). The incidence of AKI in low-, medium-, or high-PEEP patients were 16%, 38%, and 59%, respectively (p = 0.002). In a multivariate analysis, high-PEEP patients showed a higher risk of developing AKI than low-PEEP patients (OR = 4.96 [1.1-21.9] 95% CI p < 0.05). ICU mortality rate was higher in high-PEEP patients, compared to medium-PEEP or low-PEEP patients (69% vs. 44% and 42%, respectively; p = 0.057). CONCLUSION: The use of high PEEP in Covid-19 ICU patients is associated with a fivefold higher risk of AKI, leading to higher mortality. The cause and effect relationship needs further analysis.

Lung histopathologic clusters in severe COVID-19: a link between clinical picture and tissue damage.

BACKGROUND: Autoptic pulmonary findings have been described in severe COVID-19 patients, but evidence regarding the correlation between clinical picture and lung histopathologic patterns is still weak. METHODS: This was a retrospective cohort observational study conducted at the referral center for infectious diseases in northern Italy. Full lung autoptic findings and clinical data of patients who died from COVID-19 were analyzed. Lung histopathologic patterns were scored according to the extent of tissue damage. To consider coexisting histopathologic patterns, hierarchical clustering of histopathologic findings was applied. RESULTS: Whole pulmonary examination was available in 75 out of 92 full autopsies. Forty-eight hospitalized patients (64%), 44 from ICU and four from the medical ward, had complete clinical data. The histopathologic patterns had a time-dependent distribution with considerable overlap among patterns. Duration of positive-pressure ventilation (p < 0.0001), mean positive end-expiratory pressure (PEEP) (p = 0.007), worst serum albumin (p = 0.017), interleukin 6 (p = 0.047), and kidney SOFA (p = 0.001) differed among histopathologic clusters. The amount of PEEP for long-lasting ventilatory treatment was associated with the cluster showing the largest areas of early and late proliferative diffuse alveolar damage. No pharmacologic interventions or comorbidities affected the lung histopathology. CONCLUSIONS: Our study draws a comprehensive link between the clinical and pulmonary histopathologic findings in a large cohort of COVID-19 patients. These results highlight that the positive end-expiratory pressures and the duration of the ventilatory treatment correlate with lung histopathologic patterns, providing new clues to the knowledge of the pathophysiology of severe SARS-CoV-2 pneumonia.

Autonomic biomarkers of shock in idiopathic systemic capillary leak syndrome.

OBJECTIVE: The term Idiopathic Systemic Capillary Leak Syndrome (ISCLS) refers to an uncommon condition of severe distributive shock, resulting from an abrupt shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesise that the autonomic nervous system (ANS) fails in regulating the response to hypovolemia in acute ISCLS and that ANS variables characterise the progression to the recovery. DESIGN: Prospective cohort study of patients admitted to ICU for severe ISCLS flares. SETTING: Single, referral center in Italy for ISCLS. PATIENTS: Analysis of cardiovascular signals recorded during seven severe ISCLS attacks and one prodromal period in five patients. INTERVENTIONS: ANS was studied non-invasively by means of heart rate variability (HRV) and blood pressure variability analysis, as an estimation of vagal and sympathetic modulation directed to the heart and vessels. Heart rate and systolic arterial pressure (SAP) variability were also used to assess baroreflex sensitivity. ANS variables were measured during the subsequent phases which characterise ISCLS flares, namely the acute phase, the post-acute phase, and the recovery phase. MEASUREMENTS AND MAIN RESULTS: HRV was severely depressed during the acute phase accounting for the loss of ANS modulation during massive capillary extravasation. This phase was characterised by shock and impaired baroreflex control, which allowed SAP to oscillate driven by respiratory activity. Impending shock and transition from shock to a post-acute phase were marked by change of baroreflex spectral variables. The baroreflex control was fully restored during recovery. CONCLUSIONS: ANS modulation and baroreflex control are severely impaired during the acute haemodynamic instability which characterises ISCLS crises and their progressive restoration may be a clue of improvement. ANS indices during ISCLS flares might serve as useful biomarkers, able to timely announce the transition from one phase to the subsequent one, thus helping to adapt therapy accordingly.

Transesophageal echocardiography in patients with cardiac arrest: from high-quality chest compression to effective resuscitation.

BACKGROUND: Survival after cardiac arrest depends on prompt and effective cardiopulmonary resuscitation (CPR). Transesophageal echocardiography (TEE) can be applied to evaluate the effectiveness of chest compression-decompression maneuvers in the setting of cardiac arrest undergoing CPR. The efficacy of chest compression can be continuously assessed by TEE that can improve the effectiveness of CPR guiding the rescuer to optimize or correct chest compression and decompression by directly examining the movements of the cardiac walls and valve leaflets. PURPOSE: The review describes how to perform TEE in the emergency setting of cardiopulmonary arrest, its advantages, and limitations, and ultimately propose an echo-guided approach to CPR.

Tethering role of the autonomic nervous system on cardioventilatory coupling.

Hypovolemia and intermittent positive pressure ventilation are conditions that frequently characterize the state of critical illness, but their interaction and resulting cardioventilatory coupling is poorly understood even in healthy humans. We explored heart rate variability, baroreflex activity, and their interaction in an experimental protocol involving twelve mildly hypovolemic healthy subjects during spontaneous breathing and noninvasive positive-pressure ventilation. In seven subjects, an echocardiographic assessment was also performed. Correction of hypovolemia, raising cardiac preload, produced an increase in high-frequency spectral power density of heart rate, left low-frequency spectral power density unchanged but enhanced baroreflex sensitivity. Cardioventilatory coupling was affected by both central blood volume and ventilatory mode and was mainly entrained by the respiratory oscillation. In conclusion, the autonomic nervous system and baroreflex have a significant role in compensating the hemodynamic perturbation due to changes of volemia and ventilatory-induced fluctuations of venous return. They exert an integrative function on the adaptive pattern of cardioventilatory coupling.

Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status.

SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94 % in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: A prospective cohort study.

Italy was the first European country hit by the COVID-19 pandemic and has the highest number of recorded COVID-19 deaths in Europe. This prospective cohort study of the correlates of the risk of death in COVID-19 patients was conducted at the Infectious Diseases and Intensive Care units of Luigi Sacco Hospital, Milan, Italy. The clinical characteristics of all the COVID-19 patients hospitalised in the early days of the epidemic (21 February -19 March 2020) were recorded upon admission, and the time-dependent probability of death was evaluated using the Kaplan-Meier method (censored as of 20 April 2020). Cox proportional hazard models were used to assess the factors independently associated with the risk of death. Forty-eight (20.6 %) of the 233 patients followed up for a median of 40 days (interquartile range 33-47) died during the follow-up. Most were males (69.1 %) and their median age was 61 years (IQR 50-72). The time-dependent probability of death was 19.7 % (95 % CI 14.6-24.9 %) 30 days after hospital admission. Age (adjusted hazard ratio [aHR] 2.08, 95 % CI 1.48-2.92 per ten years more) and obesity (aHR 3.04, 95 % CI 1.42-6.49) were independently associated with an increased risk of death, which was also associated with critical disease (aHR 8.26, 95 % CI 1.41-48.29), C-reactive protein levels (aHR 1.17, 95 % CI 1.02-1.35 per 50 mg/L more) and creatinine kinase levels above 185 U/L (aHR 2.58, 95 % CI 1.37-4.87) upon admission. Case-fatality rate of patients hospitalized with COVID-19 in the early days of the Italian epidemic was about 20 %. Our study adds evidence to the notion that older age, obesity and more advanced illness are factors associated to an increased risk of death among patients hospitalized with COVID-19.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

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 on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

The effects of severe hemoconcentration on acid-base equilibrium in critically ill patients: the forgotten role of buffers in whole blood.

PURPOSE: Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a paroxysmal permeability disorder characterized by abrupt onset of shock and hemoconcentration due to massive shift of fluids and proteins from the intravascular to the interstitial compartment. We hypothesize that increased hemoglobin concentration has a pivotal role in the acid-base imbalance during life-threatening crises. MATERIALS AND METHODS: Analysis of the acid-base balance fluctuations during six severe ISCLS flares admitted to ICU of a referral center for ISCLS. RESULTS: Acid-base equilibrium was assessed for plasma and the whole blood by single and multicompartmental models. The acute phase of ISCLS was characterized by shock, hypoalbuminemia, severe hemoconcentration, and acidosis. The physical-chemical approach for plasma found a remarkable component of unmeasured anions (SIG) during the acute phase. After correction of the physical-chemical model for the whole blood, the SIG variations disappeared because the buffer role of hemoglobin was relevant. CONCLUSION: Hemoglobin has a remarkable role in buffering metabolic acidosis during the shock phase of ISCLS. In these circumstances, the assessment of acid-base equilibrium in plasma alone may overestimate unmeasured anions. On the contrary, the physical-chemical model corrected for whole blood better explains the metabolic component of acid-base imbalance when marked shift of hemoglobin concentration occurs.

Myocardial edema in paroxysmal permeability disorders: The paradigm of Clarkson's disease.

PURPOSE: Paroxysmal Permeability Disorders (PPDs) comprise a variety of diseases characterized by recurrent and transitory increase of endothelial permeability. Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a rare PPD that leads to an abrupt massive shift of fluids and proteins from the intravascular to the interstitial compartment. In some cases, tissue edema may involve the myocardium, but its role in the development of shock has not been elucidated so far. MATERIALS AND METHODS: Assessment of cardiac involvement during ten life-threatening ISCLS episodes admitted to ICU. RESULTS: Transthoracic echocardiographic examination was performed in eight episodes, whereas a poor acoustic window prevented cardiac ultrasound assessment in two episodes. Myocardial edema was detected by echocardiography in eight episodes and marked pericardial effusion in one-episode. Cardiac magnetic resonance showed diffuse myocardial edema in another episode. In one case, myocardial edema caused fulminant left ventricular dysfunction, which required extracorporeal life support. The mean septum thickness was higher during the shock phase compared to the recovery phase [15.5 mm (13.1-21 mm) vs. 9.9 mm (9-11.3 mm), p = .0003]. Myocardial edema resolved within 72 h. CONCLUSIONS: During early phases of ISCLS, myocardial edema commonly occurs and can induce transient myocardial dysfunction, potentially contributing to the pathogenesis of shock.

Kinetics of manual and automated mechanical chest compressions.

AIM: Early onset of adequate chest compression is mandatory for cardiopulmonary resuscitation (CPR) following cardiac arrest. Transmission of forces from chest strain to the heart may be variable between manual and mechanical chest compressions. Furthermore, automated mechanical chest devices can deliver an active decompression, thus improving the venous return to the heart. This pilot study investigated the kinetics of cardiac deformation during these two CPR methods. METHODS: Transesophageal echocardiographic analysis of the right ventricular wall behind the sternum during CPR was assessed during manual and mechanical chest compression in adult patients admitted to the emergency department for out-of-hospital cardiac arrest. RESULTS: 9 patients had manual and 11 mechanical chest compression. Mechanical chest compression was characterized by greater right ventricular lateral wall displacement [with a median (IQR) of 3.7 (3.12-4.27) vs. 2.53 (2.27-2.6) cm, p < 0.0001], and lower rising time [123 (102-169) vs. 187 (164-215) ms, p = 0.002], relaxing time [109 (102-127) vs. 211 (133-252) ms, p = 0.0003], compression rate [100.6 (99.6-102.2) vs. 131.9 (125.4-151.4) bpm, p < 0.0001], with compression-decompression time ratio of [1.04 (0.86-1.1) vs. 0.86 (0.78-0.96), p = 0.046]. CONCLUSION: Mechanical compared to manual chest compression delivered a more rapid compression and decompression of the cardiac structures at an adequate rate, with broader inward-outward movement of the ventricular walls suggesting greater emptying and filling of the ventricles. Transesophageal echocardiography may be a useful tool to assess the adequacy of chest compression without CPR interruption.