Early prolonged prone position in noninvasively ventilated patients with SARS-CoV-2-related moderate-to-severe hypoxemic respiratory failure: clinical outcomes and mechanisms for treatment response in the PRO-NIV study.

BACKGROUND: Whether prone position (PP) improves clinical outcomes in COVID-19 pneumonia treated with noninvasive ventilation (NIV) is unknown. We evaluated the effect of early PP on 28-day NIV failure, intubation and death in noninvasively ventilated patients with moderate-to-severe acute hypoxemic respiratory failure due to COVID-19 pneumonia and explored physiological mechanisms underlying treatment response. METHODS: In this controlled non-randomized trial, 81 consecutive prospectively enrolled patients with COVID-19 pneumonia and moderate-to-severe (paO2/FiO2 ratio < 200) acute hypoxemic respiratory failure treated with early PP + NIV during Dec 2020-May 2021were compared with 162 consecutive patients with COVID-19 pneumonia matched for age, mortality risk, severity of illness and paO2/FiO2 ratio at admission, treated with conventional (supine) NIV during Apr 2020-Dec 2020 at HUMANITAS Gradenigo Subintensive Care Unit, after propensity score adjustment for multiple baseline and treatment-related variables to limit confounding. Lung ultrasonography (LUS) was performed at baseline and at day 5. Ventilatory parameters, physiological dead space indices (DSIs) and circulating inflammatory and procoagulative biomarkers were monitored during the initial 7 days. RESULTS: In the intention-to-treat analysis. NIV failure occurred in 14 (17%) of PP patients versus 70 (43%) of controls [HR = 0.32, 95% CI 0.21-0.50; p < 0.0001]; intubation in 8 (11%) of PP patients versus 44 (30%) of controls [HR = 0.31, 95% CI 0.18-0.55; p = 0.0012], death in 10 (12%) of PP patients versus 59 (36%) of controls [HR = 0.27, 95% CI 0.17-0.44; p < 0.0001]. The effect remained significant within different categories of severity of hypoxemia (paO2/FiO2 < 100 or paO2/FiO2 100-199 at admission). Adverse events were rare and evenly distributed. Compared with controls, PP therapy was associated with improved oxygenation and DSIs, reduced global LUS severity indices largely through enhanced reaeration of dorso-lateral lung regions, and an earlier decline in inflammatory markers and D-dimer. In multivariate analysis, day 1 CO2 response outperformed O2 response as a predictor of LUS changes, NIV failure, intubation and death. CONCLUSION: Early prolonged PP is safe and is associated with lower NIV failure, intubation and death rates in noninvasively ventilated patients with COVID-19-related moderate-to-severe hypoxemic respiratory failure. Early dead space reduction and reaeration of dorso-lateral lung regions predicted clinical outcomes in our study population. CLINICAL TRIAL REGISTRATION: ISRCTN23016116 . Retrospectively registered on May 1, 2021.

Acute Heart Failure in the Emergency Department: the SAFE-SIMEU Epidemiological Study.

BACKGROUND: Patients with acute heart failure (AHF) have high rates of attendance to emergency departments (EDs), with significant health care costs. OBJECTIVES: We aimed to describe the clinical characteristics of patients attending Italian EDs for AHF and their diagnostic and therapeutic work-up. METHODS: We carried out a retrospective analysis on 2683 cases observed in six Italian EDs for AHF (January 2011 to June 2012). RESULTS: The median age of patients was 84 years (interquartile range 12), with females accounting for 55.8% of cases (95% confidence interval [CI] 53.5-57.6%). A first episode of AHF was recorded in 55.3% (95% CI 55.4-57.2%). Respiratory disease was the main precipitating factor (approximately 30% of cases), and multiple comorbidities were recorded in > 50% of cases (history of acute coronary syndrome, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, valvular heart disease). The treatment was based on oxygen (69.7%; 67.9-71.5%), diuretics (69.2%; 67.9-71.5%), nitroglycerin (19.7%; 18.3-21.4%), and noninvasive ventilation (15.2%; 13.8-16.6%). Death occurred within 6 h in 2.5% of cases (2.0-3.1%), 6.4% (5.5-7.3%) were referred to the care of their general practitioners within a few hours from ED attendance or after short-term (< 24 h) observation 13.9% (12.6-15.2%); 60.4% (58.5-62.2%) were admitted to the hospital, and 16.8% (15.4-18.3%) were cared for in intensive care units according to disease severity. CONCLUSIONS: Our study reporting the "real-world" clinical activity indicates that subjects attending the Italian EDs for AHF are rather different from those reported in international registries. Subjects are older, with a higher proportion of females, and high prevalence of cardiac and noncardiac comorbidities.

After the first wave and beyond lockdown: long-lasting changes in emergency department visit number, characteristics, diagnoses, and hospital admissions.

The first wave (FW) of COVID-19 led to a rapid reduction in total emergency department (ED) visits and hospital admissions for other diseases. Whether this represented a transient "lockdown and fear" phenomenon, or a more persisting trend, is unknown. We divided acute from post-wave changes in ED flows, diagnoses, and hospital admissions, in an Italian city experiencing a FW peak followed by nadir. This multicenter, retrospective, cross-sectional study involved five general EDs of a large Italian city (January-August 2020). Percent changes were calculated versus 2019, using four 14-day periods (FW peak, early/mid/late post-wave). ED visits were 147,446 in 2020, versus 214,868 in 2019. During the FW peak, visits were reduced by 66.4% (P < 0.001). The drop was maximum during daytime (69.8%) and for pediatric patients (89.4%). Critical triage codes were unchanged. Reductions were found for all non-COVID-19 diagnoses. Non-COVID-19 hospital admissions were reduced by 39.5% (P < 0.001), involving all conditions except hematologic, metabolic/endocrine, respiratory diseases, and traumas. In the early, mid, and late post-wave periods, visits were reduced by 25.4%, 25.3% and 23.5% (all P < 0.001) respectively. In the late period, reduction was greater for female (27.9%) and pediatric patients (44.6%). Most critical triage codes were unchanged. Oncological, metabolic/endocrine, and hematological diagnoses were unchanged, while other diagnoses had persistent reductions. Non-COVID-19 hospital admissions were reduced by 12.8% (P = 0.001), 6.3% (P = 0.1) and 12.2% (P = 0.001), respectively. Reductions in ED flows, led by non-critical codes, persisted throughout the summer nadir of COVID-19. Hospital admissions for non-COVID-19 diseases had transient changes.

Asymmetric deprotonation using s-BuLi or i-PrLi and chiral diamines in THF: the diamine matters.

The solution structures of [(6)Li]-i-PrLi complexed to (-)-sparteine and the (+)-sparteine surrogate in Et(2)O-d(10) and THF-d(8) at -80 °C have been determined using (6)Li and (13)C NMR spectroscopy. In Et(2)O, i-PrLi/(-)-sparteine is a solvent-complexed heterodimer, whereas i-PrLi/(+)-sparteine surrogate is a head-to-tail homodimer. In THF, there was no complexation of (-)-sparteine to i-PrLi until ≥3.0 equiv (-)-sparteine and with 6.0 equiv (-)-sparteine, a monomer was characterized. In contrast, the (+)-sparteine surrogate readily complexed to i-PrLi in THF, and with 1.0 equiv (+)-sparteine surrogate, complete formation of a monomer was observed. The NMR spectroscopic study suggested that it should be possible to carry out highly enantioselective asymmetric deprotonation reactions using i-PrLi or s-BuLi/(+)-sparteine surrogate in THF. Hence, three different asymmetric deprotonation reactions (lithiation-trapping of N-Boc pyrrolidine, an O-alkyl carbamate, and a phosphine borane) were investigated; it was shown that reactions with (-)-sparteine in THF proceeded with low enantioselectivity, whereas the corresponding reactions with the (+)-sparteine surrogate occurred with high enantioselectivity. These are the first examples of highly enantioselective asymmetric deprotonation reactions using organolithium/diamine complexes in THF.

Asymmetric deprotonation of N-boc piperidine: react IR monitoring and mechanistic aspects.

The high yielding asymmetric deprotonation trapping of N-Boc piperidine is successfully realized using s-BuLi and a (+)-sparteine surrogate. Monitoring of the lithiation by in situ React IR allowed the direct observation of a prelithiation complex.

A silver nanoparticle-poly(methyl methacrylate) based colorimetric sensor for the detection of hydrogen peroxide.

A colorimetric sensor based on nanoparticles was developed for the detection of hydrogen peroxide. Nanoparticles were made using small sheets of poly(methyl methacrylate) (PMMA) and silver nitrate. The optical properties of the solution were characterized by spectrophotometer using the localized surface plasmon resonance (LSPR) phenomenon. The shape and size of the nanoparticles were obtained using a transmission electron microscope (TEM). Silver-poly(methyl methacrylate) nanoparticles solution (AgNP-PMMA) proved to be particularly sensitive to hydrogen peroxide compared to other analytes. This sensor provided a quick, practical and easy tool to detect hydrogen peroxide.

How to manage patients on rivaroxaban in the emergency department: a statement of the Italian society of emergency medicine advisory board.

Rivaroxaban, a new oral anticoagulant, has been approved in many countries and its everyday use in clinical practice is increasing. Thus, the chances for an emergency physician to encounter rivaroxaban-treated patients in emergency situations have increased. Here, the authors address the main issues in terms of the prescription of rivaroxaban and the management of these patients in cases of minor or major bleeding, urgent surgery, atrial fibrillation requiring cardioversion, acute ischemic stroke, ST-elevation myocardial infarction, and new onset of atrial fibrillation in recent ST-elevation myocardial infarction. The recommendations reached are based on a literature review and a panel discussion of the advisory board of SIMEU, the Italian Society of Emergency Medicine.

Acute heart failure in the emergency department: a follow-up study.

Acute heart failure (AHF) is a major public health issue due to high incidence and poor prognosis. Only a few studies are available on the long-term prognosis and on outcome predictors in the unselected population attending the emergency department (ED) for AHF. We carried out a 1-year follow-up analysis of 1234 consecutive patients from selected Italian EDs from January 2011 to June 2012 for an episode of AHF. Their prognosis and outcome-associated factors were tested by Cox proportional hazard model. Patients' mean age was 84, with 66.0% over 80 years and 56.2% females. Comorbidities were present in over 50% of cases, principally a history of acute coronary syndrome, chronic obstructive pulmonary disease, diabetes, chronic kidney disease, valvular heart disease. Death occurred within 6 h in 24 cases (1.9%). At 30-day follow-up, death was registered in 123 cases (10.0%): 110 cases (89.4%) died of cardiovascular events and 13 (10.6%) of non-cardiovascular causes (cancer, gastrointestinal hemorrhages, sepsis, trauma). At 1-year follow-up, all-cause death was recorded in 50.1% (over 3 out of 4 cases for cardiovascular origin). Six variables (older age, diabetes, systolic arterial pressure <110 mm/Hg, high NT pro-BNP, high troponin levels and impaired cognitive status) were selected as outcome predictors, but with limited discriminant capacity (AUC = 0.649; SE 0.015). Recurrence of AHF was registered in 31.0%. The study identifies a cluster of variables associated with 1-year mortality in AHF, but their predictive capacity is low. Old age and the presence of comorbidities, in particular diabetes are likely to play a major role in dictating the prognosis.

Evaluation of patient skin breakdown and comfort with a new face mask for non-invasive ventilation: a multi-center study.

OBJECTIVE: To evaluate patient comfort, skin breakdown and eye irritation when comparing a prototype face mask (PM) and conventional face masks (CMs) during non-invasive ventilation. SETTING AND DESIGN: Eight centers (intensive or intermediate care units). Multicenter randomized study. POPULATIONS: Patients with acute respiratory failure of different etiologies. INTERVENTIONS: Patients were randomized to CMs or PM when ventilation was expected to last at least 12 consecutive hours a day for two consecutive days. Patient comfort, skin breakdown and eye irritation, assessed by means of standardized scoring systems, were measured after 24 and 48 h and before discontinuing ventilation. RESULTS: Hundred ninety-four patients were randomized. Forty-seven patients were finally enrolled: PM (24) and CMs (23). Ventilator settings were similar in the two groups at the beginning of the treatment and after 24 and 48 h. Skin breakdown was significantly higher in the CMs group over the study period ( p<0.001). Patient comfort was higher in the PM group after 24 and 48 h ( p=0.008 and p<0.001, respectively). Eye irritation was absent in both groups after 24 h and did not differ significantly after 48 h (p=0.539). Before ventilation was discontinued skin breakdown and patient comfort were significantly higher in the CMs group, when compared to the PM group ( p<0.001 and p=0.003, respectively). Eye irritation was slightly higher in the PM versus CMs group ( p=0.21). The time on ventilation was not significantly different between the two groups ( p=0.830). CONCLUSION: The PM significantly reduced skin breakdown while improving patient comfort, compared to the CMs.

[Definition of acute heart failure]. / Definizione di scompenso cardiaco acuto.

Acute heart failure (AHF) is a potentially life-threatening condition that may arise as a deterioration of a previous heart failure or may be the first presentation of heart failure. Several causes or precipitating factors have been listed, as well as different mechanisms have been described, thus leading to a broad spectrum of clinical presentations. Symptoms and signs of AHF have a strong clinical and prognostic significance and are kept into consideration to guide disease management. In particular, a higher clinical severity or a worse prognosis are associated with lower blood pressure levels, fluid overload, evidence of myocardial ischemia or renal impairment. Putatively, interventions addressed to restore these factors may play a role in the management of AHF.

[Acute heart failure clinical pathways, hospital funding and accreditation standards]. / Analisi di percorsi, sistemi di finanziamento ed accreditamento.

Background. The aim of this study was to analyze the formalization of hospital pathways for patients with acute heart failure (AHF) and to describe standards of accreditation and funding of the providers. Methods. This study was carried out in 10 Italian Regions, through the analysis of regional determination and grey literature. Results. Pathway standardization is mainly present for patients with chronic heart failure; only the Piedmont and Emilia Romagna Regions provide a formal standardization for patients with AHF. Among the analyzed Regions, there were no differences in the start of the management process for AHF, including hospital admission. Conversely, several differences were observed among Regions in the organization of Short Way Observation (both in terms of duration and supply), the possibility of alternative modality of admission (e.g. "home hospitalization") and the funding rules of emergency departments. Conclusions. These above stressed differences are likely to have a significant impact on the optimal management of patients with AHF.

A catalytic and tert-butoxide ion-mediated amidation of aldehydes with para-nitro azides.

We report here a new catalytic reaction in which, para-nitro azides are acylated by aldehydes to produce amides and molecular nitrogen in a single step. The transformation is believed to proceed via an electron transfer process mediated by the tert-butoxide ion, and catalysed by a thiazolium salt derived species.

Amines bearing tertiary substituents by tandem enantioselective carbolithiation-rearrangement of vinylureas.

In the presence of (-)-sparteine or a (+)-sparteine surrogate, organolithiums add to N-alkenyl-N'-arylureas to give benzylic organolithiums in an enantioselective manner. Under the influence of DMPU, these organolithiums undergo rearrangement with migration of the N'-aryl ring from N to C, leading to the urea derivatives of enantiomerically enriched amines bearing tertiary substituents. Basic hydrolysis returns the functionalized amine, providing a new synthetic route to compounds with quaternary stereogenic centers bearing nitrogen.

Mechanical determinants of early acute ventilatory failure in COPD patients: a physiologic study.

OBJECTIVE: The purpose of this study is to investigate the respiratory mechanics, breathing pattern, and pressure-generating capacity of respiratory muscles during the early phases of an acute exacerbation of COPD. DESIGN: Prospective study. SETTING: Division of Emergency Critical Care and Chronic Ventilator Unit. PATIENTS: A total of 24 COPD patients: nine patients requiring ventilatory support because of acute respiratory acidosis due to COPD exacerbation (NPPV group, pH 7.28 +/- 0.02); seven patients successfully managed with medical therapy only (SB group, pH 7.39 +/- 0.04); eight clinically stable, long term mechanically ventilated, COPD patients (IPPV group). MEASUREMENTS: Respiratory mechanics during a period of unsupported breathing. RESULTS: A rapid shallow breathing, in the presence of a high drive to breath and a high diaphragmatic tension-time index (TT(di)), was found in NPPV and IPPV groups compared to the SB group (f/V (T) ratio: 118 +/- 43 and 137 +/- 65, respectively, versus 37 +/- 12 breaths/min/L; P (0.1): 5.0 +/- 1.0 and 5.4 +/- 1.4, respectively, versus 2.2 +/- 0.2 cmH(2)O, TT(di): 0.168 +/- 0.035 and 0.161 +/- 0.039, respectively, versus 0.057 +/- 0.033); at variance, PEEPi(dyn) was greater in IPPV compared to the other two groups. A significant relationship was observed between TT(di) ratio and f/V (T) (Rho 0.756). CONCLUSION: During the early phases of an acute exacerbation, patients with COPD and acute respiratory failure had an imbalance between the decreased capacity of the respiratory muscles to generate pressure and the increased respiratory load. This imbalance was similar to that recorded in patients with COPD and chronic ventilatory failure. In both groups, the imbalance was associated with rapid shallow breathing. Among the mechanical constraints to ventilation, only PEEPi,dyn was different between acute and chronic patients with ventilatory failure.

Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial.

Studies employing noninvasive pressure support ventilation in cardiogenic pulmonary edema have been performed in the intensive care unit when overt respiratory failure is already present and in small groups of patients. In this multicenter study, performed in emergency departments, 130 patients with acute respiratory failure were randomized to receive medical therapy plus O2 (65 patients) or noninvasive pressure support ventilation (65 patients). The primary end point was the need for intubation; secondary end points were in-hospital mortality and changes in some physiological variables. Noninvasive pressure support ventilation improved PaO2/FIO2, respiratory rate, and dyspnea significantly faster. Intubation rate, hospital mortality, and duration of hospital stay were similar in the two groups. In the subgroup of hypercapnic patients noninvasive pressure support ventilation improved PaCO2 significantly faster and reduced the intubation rate compared with medical therapy (2 of 33 versus 9 of 31; p=0.015). Adverse events, including myocardial infarction, were evenly distributed in the two groups. We conclude that during acute respiratory failure due to cardiogenic pulmonary edema the early use of noninvasive pressure support ventilation accelerates the improvement in PaO2/FIO2, PaCO2, dyspnea, and respiratory rate, but does not affect the overall clinical outcome. Noninvasive pressure support ventilation does, however, reduce the intubation rate in the subgroup of hypercapnic patients.