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Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24.sup.th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HR.sub.OW). Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO.sub.2 /FiO.sub.2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n = 29, 22.3%), methylprednisolone (n = 45, 34.6%), or both (n = 56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HR.sub.OW 0.48, 95%CI, 0.23-0.99; p = 0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HR.sub.OW 0.41, 95%CI: 0.19-0.89, p = 0.025. Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.

COVID-19 respiratory failure is a life-threatening condition. Oxygenation targets were evaluated in a non-ICU setting. In this retrospective, observational study, we enrolled all patients admitted to the University Hospital of Genoa, Italy, between 1 February and 31 May 2020 with an RT-PCR positive for SARS-CoV-2. PaO2, PaO2/FiO2 and SatO2% were collected and analyzed at time 0 and in case of admission, patients who required or not C-PAP (groups A and B) were categorized. Each measurement was correlated to adverse outcome. A total of 483 patients were enrolled, and 369 were admitted to hospital. Of these, 153 required C-PAP and 266 had an adverse outcome. Patients with PaO2 <60 and >100 had a higher rate of adverse outcome at time 0, in groups A and B (OR 2.52, 3.45, 2.01, respectively). About the PaO2/FiO2 ratio, the OR for < 300 was 3.10 at time 0, 4.01 in group A and 4.79 in group B. Similar odds were found for < 200 in any groups and < 100 except for group B (OR 11.57). SatO2 < 94% showed OR 1.34, 3.52 and 19.12 at time 0, in groups A and B, respectively. PaO2 < 60 and >100, SatO2 < 94% and PaO2/FiO2 ratio < 300 showed at least two- to three-fold correlation to adverse outcome. This may provide simple but clear targets for clinicians facing COVID-19 respiratory failure in a non ICU-setting.

Background The primary objective of the study is to describe the cellular characteristics of bronchoalveolar lavage fluid (BALF) of COVID-19 patients requiring invasive mechanical ventilation; the secondary outcome is to describe BALF findings between survivors vs non-survivors. Materials and methods Patients positive for SARS-CoV-2 RT PCR, admitted to ICU between March and April 2020 were enrolled. At ICU admission, BALF were analyzed by flow cytometry. Univariate, multivariate and Spearman correlation analyses were performed. Results Sixty-four patients were enrolled, median age of 64 years (IQR 58–69). The majority cells in the BALF were neutrophils (70%, IQR 37.5–90.5) and macrophages (27%, IQR 7–49) while a minority were lymphocytes, 1%, TCD3+ 92% (IQR 82–95). The ICU mortality was 32.8%. Non-survivors had a significantly older age ( p  = 0.033) and peripheral lymphocytes ( p  = 0.012) were lower compared to the survivors. At multivariate analysis the percentage of macrophages in the BALF correlated with poor outcome (OR 1.336, CI95% 1.014–1.759, p  = 0.039). Conclusions In critically ill patients, BALF cellularity is mainly composed of neutrophils and macrophages. The macrophages percentage in the BALF at ICU admittance correlated with higher ICU mortality. The lack of lymphocytes in BALF could partly explain a reduced anti-viral response.

Background The appropriate timing of surgery and perioperative management of patients with previous SARS-CoV-2 infection are open issues. The purpose of this document is to support the clinical decision-making process regarding the patient with previous Sars-CoV-2 infection to undergo elective surgery. The recipients of this document are physicians, nurses, healthcare personnel, and other professionals involved in the patient’s surgical process. Methods The Italian Society of Anesthesia Analgesia Resuscitation and Intensive Care (SIAARTI) selected 11 experts to reach a consensus on key aspects of this theme in adult and pediatric population. The methods of this process document were in accordance to the principles of rapid review of the scientific literature and modified Delphi method. The experts produced statements and supporting reasons in the form of an informative text. The overall list of statements was subjected to a vote in order to express the degree of consent. Results Patients should not undergo elective surgery within 7 weeks of infection unless there is the risk of a negative evolution of the disease. To mitigate the risk of postsurgical mortality, a multidisciplinary approach seemed useful in addition to the use of validated algorithms to estimate the risk of perioperative morbidity and mortality; the risk related to SARS-CoV-2 infection should be added. The risk of potential nosocomial contagion from a positive patients should also be considered when deciding to proceed with surgery. Most of the evidence came from previous SARS-CoV-2 variants, so the evidence should be considered indirect. Conclusion A balanced preoperative multidisciplinary risk–benefit evaluation is needed in patients with previous infection by SARS-CoV-2 for elective surgery.

Background Postoperative morbidity and mortality in patients undergoing surgery is high, especially in patients who are at risk of complications and undergoing major surgery. We hypothesize that perioperative, algorithm-driven, hemodynamic therapy based on individualized fluid status and cardiac output optimization is able to reduce mortality and postoperative moderate and severe complications as a major determinant of the patients’ postoperative quality of life, as well as health care costs. Methods/design This is a multi-center, international, prospective, randomized trial in 380 patients undergoing major abdominal surgery including visceral, urological, and gynecological operations. Eligible patients will be randomly allocated to two treatment arms within the participating centers. Patients of the intervention group will be treated perioperatively following a specific hemodynamic therapy algorithm based on pulse-pressure variation (PPV) and individualized optimization of cardiac output assessed by pulse-contour analysis (ProAQT© device; Pulsion Medical Systems, Feldkirchen, Germany). Patients in the control group will be treated according to standard local care based on established basic hemodynamic treatment. The primary endpoint is a composite comprising the occurrence of moderate or severe postoperative complications or death within 28 days post surgery. Secondary endpoints are: (1) the number of moderate and severe postoperative complications in total, per patient and for each individual complication; (2) the occurrence of at least one of these complications on days 1, 3, 5, 7, and 28 in total and for every complication; (3) the days alive and free of mechanical ventilation, vasopressor therapy and renal replacement therapy, length of intensive care unit, and hospital stay at day 7 and day 28; and (4) mortality and quality of life, assessed by the EQ-5D-5L™ questionnaire, after 6 months. Discussion This is a large, international randomized controlled study evaluating the effect of perioperative, individualized, algorithm-driven ,hemodynamic optimization on postoperative morbidity and mortality. Trial registration Trial registration: NCT03021525 . Registered on 12 January 2017.

We describe an uncommon severe clinical complication of sepsis – thyrotoxic storm (TS). Common biologic, pathogenic, clinical conditions that can determine sepsis can cause a TS. High circulating values of vascular cellular adhesive molecules-1 and various pro-inflammatory citochines are related with thyroid damage. During sepsis, moderate dysfunctions are not expression of actual disease, but severe damage in pituitary-thyroid hormonal axis. Thyroid stimulated hormon release, and consequent overproduction of thyroid hormones can cause TS. In critical patients, presence of hormonal dysfunctions determines more elevated clinical score of sepsis severity and higher risk of death than control groups (without thyroid disease) or survived patients.

IntroductionCandida auris (C. auris) is an emerging nosocomial pathogen, and a sharp rise in cases of colonization and infection has been registered in intensive care units (ICUs) during the ongoing coronavirus disease 2019 (COVID-19) pandemic. The unfavorable resistance profile of C. auris and the potential high mortality of C. auris infections represent an important challenge for physicians.MethodsWe conducted a single-center retrospective study including all patients admitted to ICUs with isolation of C. auris in any non-sterile body site between February 20, 2020, and May 31, 2021. The primary aim of the study was to assess the cumulative incidence of C. auris candidemia in colonized patients. The secondary aim was to identify predictors of C. auris candidemia in the study population.ResultsDuring the study period, 157 patients admitted to ICUs in our hospital became colonized with C. auris; 59% of them were affected by COVID-19. Overall, 27 patients (17%) developed C. auris candidemia. The cumulative risk of developing C. auris candidemia was > 25% at 60 days after first detection of C. auris colonization. Seven patients with C. auris candidemia (26%) also developed a late recurrent episode. All C. auris blood isolates during the first occurring episode were resistant to fluconazole and susceptible to echinocandins, while 15 (56%) were resistant to amphotericin B. During late recurrent episodes, emergent resistance to caspofungin and amphotericin B occurred in one case each. In the final multivariable model, only multisite colonization retained an independent association with the development of C. auris candidemia.ConclusionCandida auris candidemia may occur in up to one fourth of colonized critically ill patients, and multisite colonization is an independent risk factor for the development of candidemia. Implementing adequate infection control measures remains crucial to prevent colonization with C. auris and indirectly the subsequent development of infection.

Background There is a paucity of data concerning the optimal ventilator management in patients with COVID-19 pneumonia; particularly, the optimal levels of positive-end expiratory pressure (PEEP) are unknown. We aimed to investigate the effects of two levels of PEEP on alveolar recruitment in critically ill patients with severe COVID-19 pneumonia. Methods A single-center cohort study was conducted in a 39-bed intensive care unit at a university-affiliated hospital in Genoa, Italy. Chest computed tomography (CT) was performed to quantify aeration at 8 and 16 cmH 2 O PEEP. The primary endpoint was the amount of alveolar recruitment, defined as the change in the non-aerated compartment at the two PEEP levels on CT scan. Results Forty-two patients were included in this analysis. Alveolar recruitment was median [interquartile range] 2.7 [0.7–4.5] % of lung weight and was not associated with excess lung weight, PaO 2 /FiO 2 ratio, respiratory system compliance, inflammatory and thrombophilia markers. Patients in the upper quartile of recruitment (recruiters), compared to non-recruiters, had comparable clinical characteristics, lung weight and gas volume. Alveolar recruitment was not different in patients with lower versus higher respiratory system compliance. In a subgroup of 20 patients with available gas exchange data, increasing PEEP decreased respiratory system compliance (median difference, MD − 9 ml/cmH 2 O, 95% CI from − 12 to − 6 ml/cmH 2 O, p  < 0.001) and the ventilatory ratio (MD − 0.1, 95% CI from − 0.3 to − 0.1, p  = 0.003), increased PaO 2 with FiO 2  = 0.5 (MD 24 mmHg, 95% CI from 12 to 51 mmHg, p  < 0.001), but did not change PaO 2 with FiO 2  = 1.0 (MD 7 mmHg, 95% CI from − 12 to 49 mmHg, p  = 0.313). Moreover, alveolar recruitment was not correlated with improvement of oxygenation or venous admixture. Conclusions In patients with severe COVID-19 pneumonia, higher PEEP resulted in limited alveolar recruitment. These findings suggest limiting PEEP strictly to the values necessary to maintain oxygenation, thus avoiding the use of higher PEEP levels.