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Pertussis continues to be a highly contagious respiratory infection, especially in children, with cyclical peaks of disease spread every three to five years. Here, we report relevant cases of B. pertussis infection between August 2023 and January 2024, and compare them with B. pertussis prevalence in pediatric patients admitted to the Reference Italian Pediatric Hospital, located in Rome, from January 2015 to July 2023. A total of 5464 tests for B. pertussis were performed during the study period, and 6.9% were positive. At the time of the COVID-19 pandemic, there was a sharp decrease in the presence of B. pertussis, which reappeared only in August 2023, recording five new cases. All five children presented with paroxysmal cough 5 to 10 days before admission. Four patients had other mild respiratory symptoms and moderate B. pertussis DNA levels (Ct mean: 26). Only one child, with very high B. pertussis DNA levels (Ct: 9), presented with severe respiratory failure. The patients with mild/moderate infection achieved clinical recovery while the patient with the severe manifestation died of cardiac arrest. These observations highlight the reemergence of pertussis even in vaccinated countries and its association with morbidity and mortality especially in young children. This emphasizes the importance of rapid diagnosis to immediately implement appropriate treatment and monitoring of immune status. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal membrane oxygenation (ECMO) may act as a driver or propagator of systemic inflammation. In turn, cytokine release can modify thromboelastographic (TEG) tests which are commonly used for anticoagulation monitoring. In this context, antithrombin (AT) supplementation might further modify TEG. Methods: This is a pre-specified sub-study of the “Randomized Controlled Trial of Antithrombin Supplementation During Extracorporeal Membrane Oxygenation” study (investigator-initiated, randomized, single-blind, two-arm trial) conducted in two Italian ECMO referral ICUs. Adult patients requiring vv-ECMO for respiratory failure and undergoing unfractioned heparin (UFH) administration were enrolled and randomized whether to receive AT supplementation. Plasma samples for cytokine assay (IL-8, IL-10, IL-6, IL-1β, TNF-α and Pro-ADM) and heparinase TEG were collected from every patient before ECMO start, 24 h and 72 h after ECMO start, before ECMO removal, and 7 days after ECMO removal or upon ICU discharge whichever happened first. AT concentration, coagulation and clinical data were collected before ECMO start and at pre-fixed time points. Results: Thirty-nine patients were enrolled (21 treatments, 18 controls). TEG-R had a weak-to-moderate positive correlation with IL-8, IL-6, IL-10 and TNF-α and a moderate positive correlation with Pro-ADM. TEG-ANG showed a weak negative correlation with IL-8, IL-6 and TNF-α, while TEG-MA negatively correlated with IL-8, TNF-α and Pro-ADM. AT supplementation seemed to modify the association between TEG-MA and IL-8, IL-10 and Pro-ADM; conversely, AT did not affect the relationship among TEG-R or TEG-ANG and the studied cytokines. Conclusions: High concentrations of systemic cytokines correlated with longer reaction times and decreased angle and amplitude at TEG, suggesting that an increase in inflammation is related with hypocoagulability as revealed by thromboelastography. [ABSTRACT FROM AUTHOR]

Introduction: Long COVID is now recognized as a common consequence of the SARS-CoV-2 infection, but we are still far from fully understanding its pathogenesis and predictive factors. Many pathophysiological factors have been studied, including ethnicity. To our knowledge, the risk factors for Long COVID have not been studied in Southeastern Italy. Aims: The aim of this study was to evaluate the predictive factors of Long COVID in a cohort of patients from Southeastern Italy. Methods: We conducted a retrospective longitudinal study, enrolling inpatients and outpatients diagnosed with COVID-19 from June 2021 to March 2022. A total of 436 subjects were evaluated in an outpatient setting 12 weeks after a SARS-CoV-2 infection, recording comorbidities, symptoms, therapy, and clinical information. Univariate and multivariate binomial logistic regression analyses were performed on different risk factors to define the probability of developing Long COVID. Results: A total of 71.8% of patients (313) developed Long COVID, while the remaining 123 (28.3%) had a complete remission of symptoms 3 months after acute infection. During the acute phase of COVID-19, 68.3% of patients experienced respiratory failure and 81.4% received corticosteroid therapy. In a multivariate analysis, the female sex (SEX M ODD 0.513) and corticosteroids (ODD 2.25) were maintained as predictive values. Conclusions: From our data and in line with other studies, the female sex emerges as a risk factor for Long COVID in the population of Southeastern Italy. Corticosteroid therapy administered in the acute phase also appears to be associated with an increased risk of Long COVID. Although indications for the prescription of corticosteroid therapy in the acute phase were indicated by the presence of pneumonia complicated by respiratory insufficiency, there was an over-prescription of corticosteroid therapy in the real life of our cohort, with 64% of patients having respiratory insufficiency and 81% having corticosteroid therapy. We hypothesize that a synergistic link between viral infection and the side effects of corticosteroid therapy may arise in selected cases. [ABSTRACT FROM AUTHOR]

The outbreak of COVID-19 resulted in a decrease in tuberculosis notification rates globally. We compared tuberculosis incidence rates and disease severity in children seen in our centre prior and during COVID-19 pandemic.We performed a cohort study enrolling children aged under 18 years who received a diagnosis of tuberculosis (January 1st, 2010-December 31st, 2021) at our Pediatric Infectious Diseases Unit. Disease severity was evaluated based on: the classification proposed by Wiseman et al., smear positivity, presence of symptoms at presentation, lung cavitation, extrapulmonary disease, respiratory failure and need for intensive care support. Overall, 168 children (50.6% female, median age 69 months, IQR 95.4) received a diagnosis of tuberculosis, 156 (92.8%) between 2010–2019, before COVID-19 outbreak, and 12 (7.2%) between 2020–2021, during the pandemic. The annual tuberculosis notification rate dropped by 73% in 2021 (0.38/100000, 95%CI 0.1–0.96) compared with 2019 (1.46/100000, 95%CI 0.84–2.37). Compared to the pre-pandemic period, the proportion of children classified as severe was higher in 2020–2021 (5, 41.6% vs 23, 15.7%, p = 0.006) with a higher rate of respiratory failure (2, 16.7%, vs 4, 2.6%, p = 0.01) and an increased need for intensive care support (1, 8.3% vs 1, 0.6%, p = 0.01). Conclusion: During COVID-19 pandemic we observed a reduction in tuberculosis notification rate in pediatric population and a significant increase in disease severity. This scenario may be the consequence of a delay in diagnosis and an underreporting of cases, rather than the effect of a reduced transmission of tuberculosis. Children reached health-care services only in the need of urgent medical attention. What is Known: • COVID-19 pandemic had a huge impact on national health care systems, resulting in a reduction of access to medical care. What is New: • In Campania Region, Italy, a low tuberculosis incidence country, we witnessed a 75% reduction in tuberculosis notification rate during pandemic. In parallel we demonstrated a significant increase in disease severity, suggesting that the reduction in notification rate may be attributed to an underreporting of cases and consequential diagnostic delay, rather than a reduced transmission of infection. [ABSTRACT FROM AUTHOR]

Background: To explore the impact of the transition from a traditional face-to-face course delivering essential contents in pediatric critical care to a hybrid format consisting of an online pre-course self-directed learning, an online facilitated discussion, and a face-to-face edition. Methods: Attendees and faculty were surveyed after the face-to-face course and the hybrid version to evaluate the effectiveness and satisfaction of participants with the course. Results: Fifty-seven students attended multiple formats of the Pediatric Basic Course between January 2020 and October 2021 in Udine, Italy. We compared course evaluation data from the 29 attendees of the face-to-face course with the 28 of the hybrid edition. Data collected included participant demographics, participant self-assessed pre and post-course "confidence" with a range of pediatric intensive care-related activities, and their satisfaction with elements of the course. There were no statistical differences in participant demographics or pre and post-course confidence scores. Overall satisfaction with the face-to-face course was marginally higher, 4.59 vs. 4.25/5, but did not reach significance. Pre-recorded lectures which could be viewed several times, were highlighted as a positive for the hybrid course. Residents found no significant differences comparing the two courses in rating the lectures and the technical skills stations. Hybrid course facilities (online platform and uploaded material) were reported to be clear, accessible, and valuable by 87% of attendees. After six months, they still find the course relevant to their clinical practice (75%). Candidates considered the respiratory failure and mechanical ventilation modules the most relevant modules. Conclusions: The Pediatric Basic Course helps residents strengthen their learning and identify areas to improve their knowledge. Both face-to-face and hybrid model versions of the course improved attendees' knowledge and perceived confidence in managing the critically ill child. [ABSTRACT FROM AUTHOR]

Respiratory failure is the most common cause of death in patients with amyotrophic lateral sclerosis (ALS) and occurs with great variability among patients according to different phenotypic features. Early predictors of respiratory failure in ALS are important to start non-invasive ventilation (NIV). Venous serum chloride values correlate with carbonate (HCO3-) blood levels and reflect metabolic compensation of respiratory acidosis. Despite its wide availability and low cost, few data on serum chloride as a prognostic marker exist in ALS literature. In the present study, we evaluated serum chloride values at diagnosis as prognostic biomarkers for overall survival and NIV adaptation in a retrospective center-based cohort of ALS patients. We collected all ALS patients with serum chloride assessment at diagnosis, identified through the Piemonte and Valle d'Aosta Register for ALS, evaluating the correlations among serum chloride, clinical features, and other serum biomarkers. Thereafter, time-to-event analysis was modeled to predict overall survival and NIV start. We found a significant correlation between serum chloride and inflammatory status markers, serum sodium, forced vital capacity (FVC), ALS functional rating scale-revised (ALSFRS-R) item 10 and 11, age at diagnosis, and weight loss. Time-to-event analysis confirmed both in univariate analysis and after multiple confounders' adjustment that serum chloride value at diagnosis significantly influenced survival and time to NIV start. According to our analysis, based on a large ALS cohort, we found that serum chloride analyzed at diagnosis is a lowcost marker of impending respiratory decompensation. In our opinion, it should be added among the serum prognostic biomarkers that are able to stratify patients into different prognostic categories even when performed in the early phases of the disease. [ABSTRACT FROM AUTHOR]

Background: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. Methods: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. Results: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV‐B, rhinovirus, and RSV‐A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non‐invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus–bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. Conclusions: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high‐risk group of patients and to design targeted interventions. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the combined effect of awake prone positioning (PP) and noninvasive ventilation (NIV) on respiratory effort and oxygenation in COVID-19 subjects affected by acute hypoxemic respiratory failure (AHRF). Topics covered include the characteristics of the study subjects, the association of combined PP and NIV with reduced inspiratory effort and improved oxygenation, and the strengths and limitations of the study.

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients' individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Noninvasive respiratory support (NRS) has been used to treat acute respiratory failure outside the ICU, but existing data have left many knowledge gaps for managing NRS in general wards. The primary objective of this study was to describe indications, duration of treatment, and outcomes of subjects treated with NRS outside the ICU. The secondary objective was to compare outcomes based on age < 80 or ≥ 80 y. METHODS: This retrospective observational study was conducted at Maggiore della Carita University Hospital in Novara, Italy, and included all patients treated with noninvasive ventilation (NIV) or CPAP outside the ICU from November 2017 to October 2018, with 1 year of follow-up. RESULTS: Of the 570 treatments performed, 383 subjects were analyzed, 136 NIV and 247 CPAP. Subjects' median (interquartile range [IQR]) age was 79 (72-85) y, and the main diagnoses of respiratory failure were cardiogenic pulmonary edema in 128 subjects (33%), pneumonia in 99 (26%), and COPD exacerbation in 52 (14%), with a median (IQR) treatment duration of 38 (16-74) h. Rapid response team visits lasted a median (IQR) 3 (2-6) d. Interface-related pressure lesions occurred in 13% of the subjects, in no case leading to definitive treatment discontinuation. Compared with the subjects ≥ 80 y old, the younger subjects had a median (IQR) longer hospitalization (16 [10-24] d vs 13 [9-20] d; P = .003) but slightly decreased in-hospital mortality (21% vs 30%; P = .061) and a decreased post-discharged 1-year mortality in hospital survivors (25% vs 41%; P = .002), differences observed only in the subjects treated with NIV. CONCLUSIONS: In a real-life setting outside the ICU, NIV and CPAP managed by a rapid response team with a daily visit in collaboration with ward staff highly experienced in NRS allowed us to treat the subjects without major complications. Post-discharge 1-year mortality was higher in the subjects ≥ 80 y old treated with NIV for acute hypercapnic respiratory failure. [ABSTRACT FROM AUTHOR]

Introduction: Asthma, along with inhaled steroids, was initially considered a risk factor for worse clinical outcomes in COVID-19. This was related to the higher morbidity observed in asthma patients during previous viral outbreaks. This retrospective study aimed at evaluating the prevalence of asthma among patients admitted due to SARS-CoV-2 infection as well as the impact of inhaled therapies on their outcomes. Furthermore, a comparison between patients with asthma, COPD and the general population was made. Methods: All COVID-19 inpatients were recruited between February and July 2020 from four large hospitals in Northwest Italy. Data concerning medical history, the Charlson Comorbidity Index (CCI) and the hospital stay, including length, drugs and COVID-19 complications (respiratory failure, lung involvement, and the need for respiratory support) were collected, as well as the type of discharge. Results: patients with asthma required high-flow oxygen therapy (33.3 vs. 14.3%, p = 0.001) and invasive mechanical ventilation (17.9 vs. 9.5%, p = 0.048) more frequently when compared to the general population, but no other difference was observed. Moreover, asthma patients were generally younger than patients with COPD (59.2 vs. 76.8 years, p < 0.001), they showed both a lower mortality rate (15.4 vs. 39.4%, p < 0.001) and a lower CCI (3.4 vs. 6.2, p < 0.001). Patients with asthma in regular therapy with ICS at home had significantly shorter hospital stay compared to those with no treatments (25.2 vs. 11.3 days, p = 0.024). Discussion: Our study showed that asthma is not associated with worse outcomes of COVID-19, despite the higher need for respiratory support compared with the general population, while the use of ICS allowed for a shorter hospital stay. In addition, the comparison of asthma with COPD patients confirmed the greater frailty of the latter, according to their multiple comorbidities. [ABSTRACT FROM AUTHOR]

Background: The Severe Respiratory Insufficiency Questionnaire (SRI) is a multidimensional instrument for health-related quality of life (HRQL) assessment in patients with chronic respiratory failure (CRF). The SRI has originally been developed in German in 2003, but 15 translated versions have been created during the last 18 years with the exclusion of the Italian translation. Aims of the Study: The present project was aimed at creating an Italian version of the SRI. Methods: Professional forward-translation and back-translation procedures have been provided based on the original German version by independent translators, and this was followed by final reconciliation. Results: The Italian SRI contains 49 items covering 7 different subscales which can summarize to one Summary Score. Conclusions: The Italian SRI is a multidimensional instrument, which can be used for HRQL assessment in Italian-speaking patients with CRF. Validation of the Italian version of the questionnaire is formally required in the future. [ABSTRACT FROM AUTHOR]

The vaccination campaign and the new SARS-CoV-2 variants may have changed the clinical profile and outcomes of patients admitted to sub-intensive unit care. We conducted a retrospective study aimed to compare the clinical and radiological features of unvaccinated critical COVID-19 patients hospitalized during the last pandemic wave (December 2021–February 2022, No-Vax group) and before starting the vaccination campaign (March–December 2020, Pre-Vax group). The No-Vax group was also compared with vaccinated patients of the same pandemic wave (Vax group). With respect to the Pre-Vax group, the No-Vax group contained a higher percentage of smokers (p = 0.0007) and a lower prevalence of males (p = 0.0003). At admission, the No-Vax patients showed both a higher CT score of pneumonia and a worse severe respiratory failure (p < 0.0001). In the No-Vax group, a higher percentage of deaths occurred, though this was not significant. In comparison with the No-Vax group, the Vax patients were older (p = 0.0097), with a higher Charlson comorbidity index (p < 0.0001) and a significantly lower HRCT score (p = 0.0015). The percentage of deaths was not different between the two groups. The No-Vax patients showed a more severe disease in comparison with the Pre-Vax patients, and were younger and had fewer comorbidities than the Vax patients. [ABSTRACT FROM AUTHOR]

Objectives: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality.Design: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry.Setting: Seventeen PICUs in Italy.Patients: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality.Interventions: None.Measurements and Main Results: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1).Conclusions: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality. [ABSTRACT FROM AUTHOR]

Background: COVID-19 long-term sequelae are ill-defined since only a few studies have explored the long-term consequences of this disease so far. Aims: To evaluate the 6-month respiratory outcome and exercise capacity of COVID-19 acute respiratory failure (ARF) patients treated with continuous positive airway pressure (CPAP) during the first wave of the ongoing COVID-19 pandemic. Methods: A retrospective observational study included COVID-19 patients with ARF. Interventions included CPAP during hospitalisation and 6-month follow up. Frailty assessment was carried out through frailty index (FI), pO2/FiO2 during hospitalisation and at follow up, respiratory parameters, 6-min walking test (6MWT) and the modified British Medical Research Council (mMRC) and Borg scale at follow up. Results: More than half of the patients had no dyspnoea according to the mMRC scale. Lower in-hospital pO2/FiO2 correlated with higher Borg scale levels after 6MWT (- 0.27; P 0.04) at the follow-up visit. FI was positively correlated with length of hospitalisation (- 0.3; P 0.03) and negatively with the 6MWT distance walked (- 0.36; P 0.004). Conclusions: Robust and frail patients with COVID-19 ARF treated with CPAP outside the intensive care unit setting had good respiratory parameters and exercise capacity at 6-month follow up, although more severe patients had slightly poorer respiratory performance compared with patients with higher PaO2/FiO2 and lower FI. [ABSTRACT FROM AUTHOR]

The imbalance between the prevalence of patients with acute respiratory failure (ARF) and acute-on-chronic respiratory failure and the number of intensive care unit (ICU) beds requires new solutions. The increasing use of non-invasive respiratory tools to support patients at earlier stages of ARF and the increased expertise of non-ICU clinicians in other types of supportive care have led to the development of adult pulmonary intensive care units (PICUs) and pulmonary intermediate care units (PIMCUs). As in other European countries, Italian PICUs and PIMCUs provide an intermediate level of care as the setting designed for managing ARF patients without severe non-pulmonary dysfunction. The PICUs and PIMCUs may also act as step-down units for weaning patients from prolonged mechanical ventilation and for discharging patients still requiring ventilatory support at home. These units may play an important role in the on-going coronavirus disease 2019 pandemic. This position paper promoted by the Italian Thoracic Society (ITS-AIPO) describes the models, facilities, staff, equipment, and operating methods of PICUs and PIMCUs. [ABSTRACT FROM AUTHOR]

A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. C C motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO 2 /FiO 2 recorded during hospital stay, P/F nadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/F nadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/F nadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease. • CCL2 (also known as MCP-1) is involved in inflammation, angiogenesis, coagulation • CCL2 can play a role in thromboinflammatory events in severe COVID-19 • Increasing CCL2 levels correlate with D-dimer in COVID-19 • Circulating CCL2 is associated with respiratory impairment severity in COVID-19 • CCL2 is associated with unfavourable clinical outcomes in COVID-19 patients [ABSTRACT FROM AUTHOR]

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

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, PaO2/FIO2 and PaCO2 at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1-3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score 6 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk. [ABSTRACT FROM AUTHOR]

Aims and Objectives: To document the level of frailty in sub‐acute COVID‐19 patients recovering from acute respiratory failure and investigate the associations between frailty, assessed by the nurse using the Blaylock Risk Assessment Screening Score (BRASS), and clinical and functional patient characteristics during hospitalisation. Background: Frailty is a major problem in patients discharged from acute care, but no data are available on the frailty risk in survivors of COVID‐19 infection. Design: A descriptive cross‐sectional study (STROBE checklist). Methods: At admission to sub‐acute care in 2020, 236 COVID‐19 patients (median age 77 years – interquartile range 68–83) were administered BRASS and classified into 3 levels of frailty risk. The Short Physical Performance Battery (SPPB) was also administered to measure physical function and disability. Differences between BRASS levels and associations between BRASS index and clinical parameters were analysed. Results: The median BRASS index was 14.0 (interquartile range 9.0–20.0) denoting intermediate frailty (32.2%, 41.1%, 26.7% of patients exhibited low, intermediate and high frailty, respectively). Significant differences emerged between the BRASS frailty classes regards to sex, comorbidities, history of cognitive deficits, previous mechanical ventilation support and SPPB score. Patients with no comorbidities (14%) exhibited low frailty (BRASS: median 5.5, interquartile range 3.0–12.0). Age ≥65 years, presence of comorbidities, cognitive deficit and SPPB % predicted <50% were significant predictors of high frailty. Conclusions: Most COVID‐19 survivors exhibit substantial frailty and require continuing care after discharge from acute care. Relevance to clinical practice: The BRASS index is a valuable tool for nurses to identify those patients most at risk of frailty, who require a programme of rehabilitation and community reintegration. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID-19) is a global public health concern. Recently, a genome-wide association study (GWAS) was performed with participants recruited from Italy and Spain by an international consortium group. Methods: Summary GWAS statistics for 1610 patients with COVID-19 respiratory failure and 2205 controls were downloaded. In the current study, we analyzed the summary statistics with the information of loci and p-values for 8,582,968 single-nucleotide polymorphisms (SNPs), using gene ontology analysis to determine the top biological processes implicated in respiratory failure in COVID-19 patients. Results: We considered the top 708 SNPs, using a p-value cutoff of 5 × 10− 5, which were mapped to the nearest genes, leading to 144 unique genes. The list of genes was input into a curated database to conduct gene ontology and protein-protein interaction (PPI) analyses. The top ranked biological processes were wound healing, epithelial structure maintenance, muscle system processes, and cardiac-relevant biological processes with a false discovery rate < 0.05. In the PPI analysis, the largest connected network consisted of 8 genes. Through a literature search, 7 out of the 8 gene products were found to be implicated in both pulmonary and cardiac diseases. Conclusion: Gene ontology and PPI analyses identified cardio-pulmonary processes that may partially explain the risk of respiratory failure in COVID-19 patients. [ABSTRACT FROM AUTHOR]

The worldwide spread of coronavirus disease 2019 (COVID-19), caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization (WHO) in March 2020. According to clinical studies carried out in China and Italy, most patients experience mild or moderate symptoms; about a fifth of subjects develop a severe and critical disease, and may suffer from interstitial pneumonia, possibly associated with acute respiratory distress syndrome (ARDS) and death. In patients who develop respiratory failure, timely conventional oxygen therapy through nasal catheter plays a crucial role, but it can be used only in mild forms. Continuous positive airway pressure (CPAP) support or non-invasive mechanical ventilation (NIV) are uncomfortable, and require significant man–machine cooperation. Herein we describe our experience of five patients with COVID-19, who were treated with high-flow nasal cannula (HFNC) after failure of CPAP or NIV, and discuss the role of HFNC in COVID-19 patients. Our findings suggest that HFNC can be used successfully in selected patients with COVID-19-related ARDS. The reviews of this paper are available via the supplemental material section. [ABSTRACT FROM AUTHOR]

SARS2‐CoV‐2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post‐mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID‐19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS‐CoV‐2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS‐CoV‐2 triggers a series of reactions leading to striking vascular alterations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Early identification of noninvasive ventilation (NIV) outcome predictors in patients with COPD who are experiencing acute hypercapnic respiratory failure consequent to exacerbation or pneumon'a is a critical issue. The primary aim of this study was to investigate the feasibility of performing diaphragmatic ultrasound for excursion, thickness, and thickening fraction in highly dyspneic subjects with COPD admitted to the emergency department for exacerbation or pneumonia, before starting NIV (T0) and after the first (T1) and second hour (T2) of treatment. Secondarily, we determined whether these variables predicted early NIV failure. METHODS: Adult subjects with COPD admitted to the emergency department for exacerbation or pneumonia requiring NIV were eligible. Right-sided diaphragmatic excursion, bilateral thickness, thickening fraction, and arterial blood gas analyses were performed at T0, T1, and T2. Feasibility was estimated by considering the number of subjects whose diaphragmatic function could be evaluated at each time point. At T2, subjects were classified in 2 sub-groups according to early NIV failure, which was defined as the inability to achieve a pH ≥ 7.35; the ability to achieve pH ≥ 7.35 indicated NIV success. RESULTS: Of the 22 subjects enrolled, 21 under- went complete diaphragm ultrasound evaluation (ie, right excursion and bilateral thickness at T0, T1, and T2) for a total of 63 excursion and 126 thickness assessments. At T2, 12 NIV successes and 9 NIV failures were recorded. Diaphragmatic excursion was greater in NIV successes than in NIV failures at T0 (1.92 [1.22-2.54] cm versus 1.00 [0.60-1.41] cm, P = .02), at T1 (2.14 [1.76-2.77] cm versus 0.93 [0.82-1.27] cm, P = .007), and at T2 (1.99 [1.63-2.54] cm versus 1.20 [0.79-1.41] cm, P = .008), respectively. Diaphragmatic thickness and thickening fraction were similar in both groups. CONCLUSIONS: In our emergency department setting, diaphragm ultrasound was a feasible and reliable tool to monitor highly dyspneic acute hypercapnic respiratory failure subjects with COPD undergoing NIV. (ClinicalTrials.gov registration NCT03314883.) [ABSTRACT FROM AUTHOR]

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Aim: The aim of the present study is to investigate how delirium and adverse clinical events (ACE) contribute independently and in combination to functional outcomes in older patients admitted to rehabilitation settings after a hip fracture. Methods: This is a multicenter retrospective cohort study of patients aged ≥65 years admitted after hip fracture surgical repair to three Italian rehabilitation units. Delirium on admission was evaluated with the Confusion Assessment Method. ACE during the rehabilitation stay were recorded, including infections (i.e. urinary tract infections, other infections), non‐infectious ACE (i.e. cardiovascular events, respiratory failure, pulmonary embolism) and falls. A multivariable linear regression was used to evaluate the effect of ACE and delirium on functional outcome, adjusting for covariates determined a priori. Results: A total of 519 patients were included in the study. The mean ± SD age was 82.9 ± 9.4 years. ACE occurred in 277 patients (53.4%), delirium alone was present in 19 patients (3.6%). Both conditions were present in 58 patients (11.2%). Compared with patients without delirium or ACE, those with ACE or delirium were more likely to have a worse functional outcome (−6.7 Barthel Index points [−11.6; −1.7]; P = 0.008; −13.2 [−25.6; −0.8]; P = 0.038) at discharge, and patients with both conditions had an even lower Barthel Index score (−18.6 Barthel Index points [−26.9; −10.3]; P < 0.001). Conclusions: ACE and delirium are very common in older patients admitted to rehabilitation settings after hip fracture, and frequently coexist. As both ACE and delirium could impact on functional outcome, alone and in combination, a clinical geriatric approach is necessary for this population to minimize risks. Geriatr Gerontol Int 2019; 19: 404–408. [ABSTRACT FROM AUTHOR]

Abstract Background and objective Non-Invasive Ventilation (NIV) represents a standard of care to treat some acute respiratory failure (ARF). Data on its use in pneumonia are lacking, especially in a setting outside the Intensive Care Unit (ICU). The aims of this study were to evaluate the use of NIV in ARF due to pneumonia outside the ICU, and to identify risk factors for in-hospital mortality. Methods Prospective, observational study performed in 19 centers in Italy. Patients with ARF due to pneumonia treated outside the ICU with either continuous positive airway pressure (CPAP) or noninvasive positive pressure ventilation (NPPV) were enrolled over a period of at least 3 consecutive months in 2013. Independent factors related to in-hospital mortality were evaluated. Results Among the 347 patients enrolled, CPAP was applied as first treatment in 176 (50.7%) patients,NPPV in 171 (49.3%). The NPPV compared with CPAP group showed a significant higher PaCO 2 (55 [47–78] vs 37 [32–43] mmHg, p < 0.001), a lower arterial pH (7.30 [7.21–7.37] vs 7.43 [7.35–7.47], p < 0.001), higher HCO3– (28 [24–33] vs 24 [21–27] mmol/L, p < 0.001). De-novo ARF was more prevalent in CPAP group than in NPPV group (86/176 vs 31/171 patients,p < 0.001). In-hospital mortality was 23% (83/347). Do Not Intubate (DNI) order and Charlson Comorbidity Index (CCI) ≥3 were independent risk factors for in-hospital mortality. Conclusions Outside ICU setting, CPAP was used mainly for hypoxemic non-hypercapnic ARF, NPPV for hypercapnic ARF. In-hospital mortality was mainly associated to patients' basal status (DNI status, CCI) rather than the baseline degree of ARF. Highlights • In pneumonia, CPAP was used mainly for non-hypercapnic ARF, NPPV for hypercapnic ARF. • Mortality was associated to patients' basal status rather than baseline degree of ARF. • Intolerance was responsible of clinical failure and death in only 5/60 cases (8%). • When CPAP failed, NPPV had a role as rescue treatment (56% survived after switch). [ABSTRACT FROM AUTHOR]

We assessed the association between weekday (WD) or weekend (WE) admission and mortality for patients hospitalized with acute pulmonary embolism (PE). Weekend included holidays. We analyzed hospital administrative data of all patients discharged with a diagnosis of PE extracted from the Italian Health Ministry database (January 2001 to December 2014). A total of 265 035 hospitalizations with a diagnosis of PE were retrieved, in which PE was the primary diagnosis in 198 565 (74.9%); 200 166 (75.5%) patients were admitted on WD and 64 869 (24.5%) on WE. Admissions for PE were more frequent on Mondays (41 917 admissions, 15.8% of all events) and less frequent on Saturdays (32 295 admissions, 12.2%) and Sundays (32 574 admissions, 12.3%). Patients admitted on WE were on average 1 year older, presented more frequently with respiratory failure, and had more common comorbidities. After adjustment for age, gender, comorbidities, and presence of respiratory failure, in-hospital mortality for patients admitted on WE was greater (odds ratio: 1.15, 95% confidence interval: 1.13-1.18; P < .001). This study supports that, in Italy, hospitalization for PE on WE is associated with a significantly higher mortality rate than on WD. [ABSTRACT FROM AUTHOR]

Background: Measles virus, member of the genus Morbillivirus in the family Paramyxoviridae, is a highly contagious human pathogen. An effective live-attenuated vaccine is available and its use has the potential to eradicate the disease from the human population. Although the vaccine was introduced in national vaccination schedules, several measles outbreaks have occurred because of insufficient vaccination coverage. Since early January 2017, a new outbreak of measles in Italy has been observed. Methods: We analyzed all the patients admitted to the Emergency Department of Bambino Gesù Children Hospital of Rome from the 1st of January 2017 to the end of May 2017 and discharged with diagnosis of suspected or confirmed measles or admitted to the Pediatric and Infectious Disease Unit. For each confirmed case, demographic data, vaccination history, exposure to source case, clinical presentation, date of onset of symptoms, hospitalization, laboratory test results, complications and therapy were collected. Results: From the 1st of January 2017 to the 31st of May 2017, we enrolled 139 patients who were conducted to the Emergency Department of Bambino Gesù Children's Hospital because of measles: 33 patients were discharged with the diagnosis of suspected measles by clinical manifestations; 33 discharged with the diagnosis of confirmed measles by laboratory tests and 73 were admitted to the Pediatric and Infectious Disease Unit. Seven patients, who were exposed to mothers with measles, were admitted to receive treatment with Measles Immune Globulin intravenously. Among the 66 patients admitted to the hospital with measles, 31 cases (47%) occurred in unvaccinated individuals who were age-eligible for measles vaccination; 29 (44%) were infants too young to be vaccinated; only five patients (8%) received one dose of measles-containing vaccine. Out of the 66 patients, 35 (53%) developed complications. Acute respiratory failure was the most reported complications (20%). Death, due to multiorgan failure by measles, occurred in one 9-girl-year-age patient with genetic disorders who was unvaccinated. Conclusions: Measles still represents a serious public health problem worldwide. Vaccination against measles is safe, effective, and cost-effective. High vaccination coverage (>95%) with two doses of measles vaccine is crucial to elimination. Health care professionals play an important role in vaccination uptake and prevention of measles spread during an outbreak. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on which lung-protective strategies should be used in cardiac surgery patients. Sparse and small randomized clinical and animal trials suggest that maintaining mechanical ventilation during cardiopulmonary bypass is protective on the lungs. Unfortunately, such evidence is weak as it comes from surrogate and minor clinical endpoints mainly limited to elective coronary surgery. According to the available data in the academic literature, an unquestionable standardized strategy of lung protection during cardiopulmonary bypass cannot be recommended. The purpose of the CPBVENT study is to investigate the effectiveness of different strategies of mechanical ventilation during cardiopulmonary bypass on postoperative pulmonary function and complications.Methods/design: The CPBVENT study is a single-blind, multicenter, randomized controlled trial. We are going to enroll 870 patients undergoing elective cardiac surgery with planned use of cardiopulmonary bypass. Patients will be randomized into three groups: (1) no mechanical ventilation during cardiopulmonary bypass, (2) continuous positive airway pressure of 5 cmH2O during cardiopulmonary bypass, (3) respiratory rate of 5 acts/min with a tidal volume of 2-3 ml/Kg of ideal body weight and positive end-expiratory pressure of 3-5 cmH2O during cardiopulmonary bypass. The primary endpoint will be the incidence of a PaO2/FiO2 ratio <200 until the time of discharge from the intensive care unit. The secondary endpoints will be the incidence of postoperative pulmonary complications and 30-day mortality. Patients will be followed-up for 12 months after the date of randomization.Discussion: The CPBVENT trial will establish whether, and how, different ventilator strategies during cardiopulmonary bypass will have an impact on postoperative pulmonary complications and outcomes of patients undergoing cardiac surgery.Trial Registration: ClinicalTrials.gov, ID: NCT02090205 . Registered on 8 March 2014. [ABSTRACT FROM AUTHOR]

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions. [ABSTRACT FROM AUTHOR]

Background: The use of case-based reimbursement for medical rehabilitation is greatly discussed. The investigators explored the relationship between disability and reimbursement opportunities in individuals with respiratory diseases undergoing in-hospital pulmonary rehabilitation (PR), considering the correlation (if any) between the Rehabilitation Complexity Scale (RCS-E v13) scores used at admission and the actual reimbursement. Methods: This study is part of a larger prospective multicenter study conducted by eight Pulmonary Rehabilitation Units in Italy. Here, investigators considered only data from the Lombardy Region. On January 30th or February 28th, 2023, participants were allocated according to the main DRG into 4 groups [tracheostomized/ventilated (TX/V), chronic respiratory failure (CRF), COPD, and miscellaneous group]. We recorded anthropometrics, diagnosis, international outcome measures, and calculated admission and discharge RCS-E v13 scores and hospital stay reimbursement according to the healthcare system (HS). Results: Three hundred and sixteen participants were evaluated. Patients were elderly, in the majority of cases with CRF, presenting comorbidities, disability, dyspnea, and reduced effort tolerance. At admission, RCS-E v13 showed an average moderate value of complexity. The median (IQR) HS reimbursement/stay was different among groups. RCSE v13 evaluated at admission was weakly (r=0.3471), but significantly related to the HS reimbursement/stay (p<0.0001) mainly due to TX/V and miscellaneous subgroups, while no relationship was found for COPD and CRF patients. After PR, all outcome measures improved significantly in all groups (p<0.001 for all). Higher RCS-E v13 scores at admission did not correspond to a proper amount of reimbursement, being this latter under- or over-estimated if compared to needs assessed by RCS-E v13. RCS-E v13 at discharge decreased for all subgroups (range from -6 to -11) reaching a low value of complexity. Conclusions: The RCS-E v13 disability score does not fully mirror the HS reimbursement for patients undergoing inhospital PR. [ABSTRACT FROM AUTHOR]

Aim To date non-invasive ( NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease ( COPD) patients with acute respiratory failure ( ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases ( ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis ( RA) admitted to an experienced rural medical ward. Methods This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria ( pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A ( pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. Results Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen per cent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate ( MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. Conclusion In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH. [ABSTRACT FROM AUTHOR]

Introduction: A leading role for non-invasive ventilation (NIV), as comfort treatment or palliative care, is actually recognized for very old patients suffering from ARF. NIV was frequently used in both ICU and respiratory ICU (RICUs) for very old patients and it is associated with a reduced rate of endotracheal intubations and mortality. This study aims to evaluate the effects of NIV, performed in a setting of half-open geriatric ward with family support, in a cohort of very old patients with ARF and DNI decision. Methods: A consecutive cohort of 20 very old patients with DNI decision was admitted in our 26-bed geriatric ward during a 6 months' period. DNI decision was obtained in emergency room with an intensive care physician supported by a psychologist. Pressure support ventilation was the first choice of NIV. NIV has been performed by three adequately trained geriatricians, with one of them experienced in ICU, and in close collaboration with intensive care physicians. Arterial blood gases, to assess the response to ventilation, were obtained after 1, 6 and 12 h. NIV settings were modified according to arterial blood gas analyses or respiratory fatigue, if needed. Results: Therefore, 75 % of patients were discharged home and 12 out of 20 patients had home respiratory support. PaO/FiO ratio and pH increased while PaCO decreased during the 12 h of NIV with statistical significance. At the admission, alive patients had PaCO significantly lower than dead patients. After 12 h, alive patients had a better pH than dead patients. Dead patients experienced more complication than survivors. Conclusion: Very old DNI patients with ARF could be treated with NIV in half-open geriatric ward with trained physicians and nurses. The presence of family members may improve patients' comfort and reduce anxiety level even at the end of life. Further studies are needed to address the effective role of NIV in very old patients with DNI decisions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Properly titrated opiates decrease respiratory rate but do not affect tidal volume or induce respiratory acidosis. OBJECTIVE: To determine whether remifentanil improves breathing pattern or reduces inspiratory effort in patients with acute respiratory failure and tachypnea or rapid shallow breathing. METHODS: We studied 14 patients who developed tachypnea and/or rapid shallow breathing if the pressure support level was reduced. During pressure support ventilation, each patient received 30-min infusions, separated by 30 min, of remifentanil and placebo. Measurements were obtained before commencing and before stopping each infusion, and after 3 min of unassisted breathing. The main outcomes were rapid shallow breathing index and change in pressure-time product. RESULTS: Remifentanil did not significantly affect tidal volume. During pressure support ventilation, remifentanil infusion reduced respiratory rate, pressure-time product, and cardiovascular double product (heart rate × systolic arterial pressure) without modifying the sedation score. Mean PaCO2 showed a small and clinically negligible increase during remifentanil, but PaCO2 increased more in the hypercapnic patients than in the normocapnic patients. Remifentanil reduced the rapid shallow breathing index after 3 min of unassisted breathing. CONCLUSIONS: Remifentanil improved respiratory pattern and decreased inspiratory muscles effort in patients with tachypnea or rapid shallow breathing, but did not affect oxygenation or sedation. Though the acid-base balance did not show clinically relevant changes on average, we cannot exclude the possibility that remifentanil might prolong weaning in hypercapnic patients. [ABSTRACT FROM AUTHOR]

Abstract: Hereditary myopathy with early respiratory failure (HMERF) is a rare disorder characterized by severe respiratory involvement at onset, muscle weakness starting in the early adulthood, and cytoplasmic bodies with peculiar immunohistochemical reactivity on muscle biopsy. Here we describe a patient who presented with hypercapnic coma at age 32. A detailed light and electron microscopy analysis on muscle biopsy was performed and, together with clinical data, led to the diagnosis. The R279W mutation in the TTN gene was excluded. This report expands the geographical region of incidence and encourages additional studies to clarify the genetic heterogeneity of the condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to test methods for generating epidemiological evidence on health conditions of small, dispersed minority communities. METHODS: We used community-based mixed methods including a cross-sectional survey in 5 purposely selected settlements of Khorakané Romá (Gypsies of Muslim culture) in Italy to study the living conditions and health status of children aged from birth to 5 years. RESULTS: In the 15 days prior to the survey, 32% of the children had suffered diarrhea and 55% had had a cough. Some 17% had experienced respiratory difficulties during the past year. Risk factors associated with these outcomes included years spent living at the camp, overcrowding, housing conditions, use of wood-burning stoves, presence of rats, and issues related to quality of sanitation and drains. Qualitative information helped define the approach and the design, and in the interpretation and consolidation of quantitative results. CONCLUSIONS: Guided by the priorities expressed by dispersed minority communities, small studies with little resources can provide a solid base to advocate for evidence-based participatory planning. Exact intervals appeared to be robust and conservative enough compared with other intervals, conferring solidity to the results. [ABSTRACT FROM AUTHOR]

Background: The analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF). Methods: The Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998-2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis. Results: The probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission. Conclusion: The time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission. [ABSTRACT FROM AUTHOR]

Non-invasive ventilation (NIV) is a safe, versatile and effective technique that can avert side effects and complications associated with endotracheal intubation. The success of NIV relies on several factors, including the type and severity of acute respiratory failure, the underlying disease, the location of treatment, and the experience of the team. The time factor is also important. NIV is primarily used to avert the need for endotracheal intubation in patients with early-stage acute respiratory failure and post-extubation respiratory failure. It can also be used as an alternative to invasive ventilation at a more advanced stage of acute respiratory failure or to facilitate the process of weaning from mechanical ventilation. NIV has been used to prevent development of acute respiratory failure or post-extubation respiratory failure. The number of days of NIV and hours of daily use differ, depending on the severity and course of the acute respiratory failure and the timing of application. In this review article, we analyse, compare and discuss the results of studies in which NIV was applied at various times during the evolution of acute respiratory failure. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of early administration of noninvasive continuous positive airway pressure (nCPAP) delivered by the helmet vs. face mask to treat hematological malignancy patients with fever, pulmonary infiltrates, and hypoxemic acute respiratory failure.Design and Setting: Prospective clinical study with historical matched controls in the hematology department of a university hospital.Patients and Interventions: Seventeen hematological malignancy patients with hypoxemic acute respiratory failure defined as: moderate to severe dyspnea, tachypnea (>30-35 breaths/min), use of accessory muscles and paradoxical abdominal motion, and PaO2/FIO2 ratio less than 200. Each patient was treated with nCPAP by helmet outside the ICU in the hematological ward. Arterial oxygen saturation, heart rate, respiratory rate, and blood pressure were monitored to identify early nCPAP failure. Seventeen historical-matched controls treated in the same department with face mask CPAP were selected as control population; matching criteria were age, sex, diagnosis, and PaO2/FIO2 ratio. Primary end-points were improvement in gas exchanges and the need for endotracheal intubation.Results: Oxygenation improved in all patients after nCPAP. No patient failed helmet nCPAP because of intolerance while eigh patients in the mask group did so. nCPAP could be applied continuously for a longer period of time in the helmet group (28.44+/-0.20 vs. 7.5+/-0.45 h).Conclusions: Early nCPAP with helmet improves oxygenation in selected immunosuppressed patients with hypoxemic acute respiratory failure. Tolerance of helmet nCPAP seems better than that of nCPAP delivered by mask. [ABSTRACT FROM AUTHOR]

Background: In Italy, respiratory intensive care units (RICUs) provide an intermediate level of care between the intensive care unit (ICU) and the general ward for patients with single organ respiratory failure. Because of the lack of official epidemiological data in these units, a two phase study was performed with the aim of describing the work profile in Italian RICUs.Methods: A national survey of RICUs was conducted from January to March 1997 using a questionnaire which comprised over 30 items regarding location, models of service provision, staff, and equipment. The following criteria were necessary for inclusion of a unit in the survey: (1) a nurse to patient ratio ranging from 1:2.5 to 1:4 per shift; (2) availability of adequate continuous non-invasive monitoring; (3) expertise for non-invasive ventilation (NIV) and for intubation in case of NIV failure; (4) physician availability 24 hours a day. Between November 1997 and January 1998 a 3 month prospective cohort study was performed to survey the patient population admitted to the RICUs.Results: Twenty six RICUs were included in the study: four were located in rehabilitation centres and 22 in general hospitals. In most, the reported nurse to patient ratio ranged from 1:2 to 1:3, with 36% of units reporting a ratio of 1:4 per shift. During the study period 756 consecutive patients of mean (SD) age 68 (12) years were admitted to the 26 RICUs. The highest proportion (47%) were admitted from emergency departments, 19% from other medical wards, 18% were transferred from the ICU, 13% from specialist respiratory wards, and 2% were transferred following surgery. All but 32 had respiratory failure on admission. The reasons for admission to the RICU were: monitoring for expected clinical instability (n=221), mechanical ventilation (n=473), and weaning (n=59); 586 patients needed mechanical ventilation during their stay in the RICU, 425 were treated with non-invasive techniques as a first line of treatment (374 by non-invasive positive pressure, 51 by iron lung), and 161 underwent invasive mechanical ventilation (63 intubated, 98 tracheostomies). All but 48 patients had chronic respiratory disease, mainly chronic obstructive pulmonary disease (COPD; n=451). More than 70% of patients (n=228) had comorbidity, mainly consisting of heart disorders. The median APACHE II score was 18 (range 1--43). The predicted inpatient mortality risk rate according to the APACHE II equation was 22.1% while the actual inpatient mortality rate was 16%. The mean length of stay in the RICU was 12 (11) days. The outcome in most patients (79.2%) admitted to RICUs was favourable.Conclusions: Italian RICUs are specialised units mainly devoted to the monitoring and treatment of acute on chronic respiratory failure by non-invasive ventilation, but also to weaning from invasive mechanical ventilation. The results of this study provide a useful insight into an increasingly important field of respiratory medicine. [ABSTRACT FROM AUTHOR]

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia., Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia., Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible., Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations., Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization., Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04)., Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

Mortality is high in Coronavirus disease 2019 patients with pre-existing comorbidities and advanced age. Associated complications have added to the negative prognosis. Nevertheless, many have fully recovered, even among the most fragile. Factors associated with their survival was investigated. Retrospective study of patients aged ≥90 years admitted for COVID-19 to the Internal Medicine wards of two hospitals in Lombardy, Italy. Among 34 patients with SARS-CoV-2 pneumonia, 33 (97.1%) had respiratory failure. Eighteen patients (52.9%) survived and 16 (47.1%) died during hospital stay. Survivors compared to deceased had a significantly longer hospitalization (19 vs. 10 days respectively; p = 0.02), a better PaO2:FiO2 ratio (241 vs. 171 respectively; p = 0.003), higher lymphocyte counts (p = 0.01) and lower serum LDH levels (p < 0.001) at admission. At multivariate analysis only higher PaO2:FiO2 was associated with survival (OR 1.06 [95%CI 1.0–1.03]; p = 0.02). Kaplan-Meier analysis showed a significant difference in event-free survival between patients treated or not with LMWH (p < 0.0001) and between those treated or not with beta-blockers (p = 0.008). Cox regression, performed in the subgroup of patients who received LMWH, did not show significant difference for sex (HR 2.7 [95% CI 0.53–14.3], p = 0.23), CCI (HR 0.7 [95% CI 0.37–1.45], p = 0.38), PaO2:FiO2 ratio (HR 0.98 [95% CI 0.97–1.0], p = 0.07), corticosteroid therapy (HR 0.99 [95% CI 0.22–4.5], p = 0.99) and beta-blocker therapy (HR 2.8 [95% CI 0.56–14,7], p = 0.21). Despite higher mortality in elderly, treatment with LMWH and betablockers might be associated with better survival. Dedicated studies are required to confirm our result. • Advanced age and comorbidities are associated to worst outcome in Covid-19. • Treatment with low molecular weight heparin improves in-hospital survival. • Beta-blockers might have a protective role in Covid-19, however, more insight is needed. • A focused supportive care to prevent thrombotic and arrhythmic complications related to Covid-19 could result in a better clinical course. [ABSTRACT FROM AUTHOR]

Objectives: Patients with acute respiratory failure due to coronavirus disease 2019 (COVID-19) have a high likelihood of needing prolonged intubation and may subsequently require tracheotomy. Indications and timing for performing tracheotomy in patients affected by severe COVID-19 pneumonia are still elusive. The aim of this study is to analyze the role of tracheotomy in the context of this pandemic. Moreover, we report the timing of the procedure and the time needed to complete weaning and decannulation in our center. Methods: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to the intensive care unit (ICU) of the tertiary care center of Reggio Emilia (Italy). All patients underwent orotracheal intubation with invasive mechanical ventilation, followed by percutaneous or open surgical tracheotomy. Indications, timing of the procedure, and time needed to complete weaning and decannulation were reported. Results: Forty-four patients were included in the analysis. Median time from orotracheal intubation to surgery was 7 (range 2-17) days. Fifteen (34.1%) patients died during the follow-up period (median 22 days, range 8-68) after the intubation. Weaning from the ventilator was first attempted on median 25th day (range 13-43) from orotracheal intubation. A median of 35 (range 18-79) days was required to complete weaning. Median duration of ICU stay was 22 (range 10-67) days. Mean decannulation time was 36 (range 10-77) days from surgery. Conclusions: Since it is not possible to establish an optimal timing for performing tracheotomy, decision-making should be made on case-by-case basis. It should be adapted to the context of the pandemic, taking into account the availability of intensive care resources, potential risks for health care workers, and benefits for the individual patient. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the short- and long-term prognosis of patients with chronic obstructive lung disease (COLD) who had noninvasive mechanical ventilation (NMV) for acute respiratory failure (ARF).Design: Retrospective study.Setting: Two respiratory intermediate intensive care units.Patients: Two groups of patients suffering from COLD and an ARF episode requiring mechanical ventilation. Group 1 (30 patients) was given NMV using face masks (aged 64 +/- 9 years; pH = 7.28 +/- 0.05; PaCO2 = 83 +/- 18 mmHg; PaO2/FIO2 = 141 +/- 61). Group 2 (27 patients) was composed of control patients (aged = 65 +/- 8 years; pH = 7.26 +/- 0.05; PaCO2 = 75 +/- 17 mmHg; PaO2/FIO2 = 167 +/- 41) given MV using endotracheal intubation (EI) when clinical and functional conditions had further deteriorated because the medical therapy failed and NMV was not available at the time. Causes of ARF were in group 1 and 2 respectively: pneumonia in 8 (27%) and 11 (41%), acute exacerbation of COLD in 19 (63%) and 14 (52%) and pulmonary embolism in 3 (10%) and 2 (7%) patients.Measurements and Results: Success rate, mortality during stay in ICU (at 3 months and at 1 year), and the need for rehospitalization during the year following ARF were measured in this study. Group 1 showed a success rate of 74%, only 8/30 patients needing EI and conventional MV. In group 2, the weaning success was 74% (20/27 patients). The mortality for group 1 was 20% in IICU, 23% at 3 months and 30% at 1 year; and 26% for group 2 in ICU, 48% at 3 months and 63% at 1 year. Within each group 1-year mortality was greater (p < 0.01) in patients with pneumonia. The number of new ICU admissions during the follow-up at 1 year was 0.12 versus 0.30 in groups 1 and 2 respectively (p < 0.05).Conclusion: For patients suffering from COLD who have undergone ARF, avoiding EI by early treatment with NMV is associated with better survival in comparison to patients bound to invasive MV. Pneumonia as a cause of ARF may worsen the prognosis in both groups of patients. [ABSTRACT FROM AUTHOR]

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets' air-dispersion and the healthcare workers' contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment. [ABSTRACT FROM AUTHOR]

An outbreak of a new coronavirus originating from Wuhan (China), responsible for a severe acute respiratory syndrome (SARS), called SARS-CoV-2, is causing a pandemic disease called CoViD-19 (Coronavirus Disease-19), although strict containment measures and restrictions on individual travel have been taken everywhere to hinder the spread of the virus. The clinical spectrum of this infection includes, in order of lesser to greater severity, asymptomatic viremia, paucisymptomatic forms, clinical conditions characterized by respiratory failure that needs mechanical ventilation and support in an intensive care unit, systemic manifestations of infection, septic shock, and multiple organ dysfunction syndromes. There is currently no vaccine to prevent CoViD-19, but the international scientific community is intensely focused on finding a vaccine that will prevent SARS-CoV-2 transmission. In the meanwhile, to prevent hospitals from risking collapse, it is crucial to stratify patients at high risk of poor lung progression, to find effective monitoring strategies, even at home, for the positive patients and/or those highly at risk of positivity of CoViD-19. Starting from the pathogenetic mechanisms involved in the development of this infection up to the clinical characteristics of the infected patients, in this review we tried to focus on the crucial points of the infection in combination with the appropriateness of the medical intervention. We aim to offer indications of therapeutic intervention that are timely and, as far as possible, effective, targeted to the individual patient in relation to age, clinical condition and comorbidities. An early diagnosis associated with an appropriate therapeutic action in the initial stages of the disease can reduce the progression of CoViD-19 towards interstitial pneumonia, thus interfering with the number of transfers to intensive care and lethality of the pandemic in progress.