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The aim of this retrospective study, conducted in an Italian tertiary care hospital, was to evaluate maternal-fetal and neonatal clinical outcomes in a group of patients with pregestational diabetes mellitus (PGDM), such as diabetes mellitus type 1 (DM1), diabetes mellitus type 2 (DM2), and maturity onset diabetes of the young (MODY). Overall, 174 pregnant women, nulliparous and multiparous, with a single pregnancy were enrolled. Data on pregnancy, childbirth, and newborns were collected from medical records. The selected patients were divided into two groups: the PGDM group (42 with DM1, 14 with DM2, and 2 with MODY), and the control group (116 patients with a negative pathological history of diabetes mellitus). We reported an incidence of preterm delivery of 55.2% in the PGDM group, including 59.5% of those with DM1 and 42.9% of those with DM2, vs. 6% in the controls. Fetal growth disorders, such as intrauterine growth retardation, small for gestational age, and fetal macrosomia were found in 19% and 3.6% in the case and control groups, respectively. A relationship between DM2 and gestational hypertension was found.

Left atrial sphericity index (LASI) is an echocardiographic index easily obtained; its use in patients with heart failure (HF) has never been investigated so far. This single-centre study aimed to investigate the usefulness of LASI in an unselected cohort of patients hospitalized for acute HF, and its potential correlation with the amino-terminal portion of pro-B-type natriuretic peptide (NT-proBNP) levels and with New York Heart Association (NYHA) functional class. Ninety-four consecutive HF patients underwent a transthoracic echocardiogram with a detailed study of the left atrium (LA) including LASI (calculated from the apical four-chamber view as the ratio between the transverse and longitudinal diameters), and blood tests (including NT-proBNP) on the same day. Median age was 75.5 (interquartile range-IQR 62-82) years and 55% were males, 58.5% had a NYHA class III-IV, and median NT-proBNP was 3284 (IQR 1215-7055) pg/ml. The LA was dilated in 94%, and median biplane LA volume index was 62 ml/m 2 . Patients with advanced NYHA class showed more advanced LA remodeling. Mean LASI was 0.78 ± 0.09 and did not correlate with NT-proBNP levels (r 0.03; p 0.75) or with patient NYHA class (R 2 0.011; p 0.287). None of the echocardiographic indices of LA structural and functional remodeling proved to be independently associated with a high NYHA class on multivariate regression analysis. In conclusion, LA remodeling is almost invariably present in patients with HF. LASI does not correlate with NT-proBNP levels or with NYHA functional class. Further studies are needed to describe the complex patterns of atrial remodeling in HF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg -1 ., Methods: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg -1 of crystalloids in 10 (FC 10 ) or 20 (FC 20 ) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (d max ), time when the d max was observed (t max ), change from baseline at 1-min (d 1 ) and 5-min (d 5 ) after FC end., Results: After FC 10 and FC 20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The d max and the t max were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end., Conclusions: The infusion time of FC administration affects fluid responsiveness, being higher for FC 10 as compared to FC 20 . The effect on flow variables of either FCs fades 5 min after the end of infusion., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

The etiology of bladder cancer is known to be associated with behavioral and environmental factors. Moreover, several studies suggested a potential role of HPV infection in the pathogenesis with controversial results. A systematic review was conducted to assess the role of HPV. A total of 46 articles that reported the prevalence of HPV infection in squamous (SCC), urothelial (UC), and transitional cell carcinomas (TCC) were selected. A pooled prevalence of 19% was found, with a significant difference in SCC that was mainly driven by HPV-16. Moreover, infection prevalence in case-control studies showed a higher risk of bladder cancer in HPV-positive cases (OR: 7.84; p-value < 0.00001). The results may suggest an etiologic role of HPV in bladder cancer. HPV vaccine administration in both sexes could be key to prevent the infection caused by high-risk genotypes.

Background: To investigate the effects of the COVID-19 lockdowns on the vasculopathic population. Methods: The Divisions of Vascular Surgery of the southern Italian peninsula joined this multicenter retrospective study. Each received a 13-point questionnaire investigating the hospitalization rate of vascular patients in the first 11 months of the COVID-19 pandemic and in the preceding 11 months. Results: 27 out of 29 Centers were enrolled. April-December 2020 (7092 patients) vs. 2019 (9161 patients): post-EVAR surveillance, hospitalization for Rutherford category 3 peripheral arterial disease, and asymptomatic carotid stenosis revascularization significantly decreased (1484 (16.2%) vs. 1014 (14.3%), p = 0.0009; 1401 (15.29%) vs. 959 (13.52%), p = 0.0006; and 1558 (17.01%) vs. 934 (13.17%), p < 0.0001, respectively), while admissions for revascularization or major amputations for chronic limb-threatening ischemia and urgent revascularization for symptomatic carotid stenosis significantly increased (1204 (16.98%) vs. 1245 (13.59%), p < 0.0001; 355 (5.01%) vs. 358 (3.91%), p = 0.0007; and 153 (2.16%) vs. 140 (1.53%), p = 0.0009, respectively). Conclusions: The suspension of elective procedures during the COVID-19 pandemic caused a significant reduction in post-EVAR surveillance, and in the hospitalization of asymptomatic carotid stenosis revascularization and Rutherford 3 peripheral arterial disease. Consequentially, we observed a significant increase in admissions for urgent revascularization for symptomatic carotid stenosis, as well as for revascularization or major amputations for chronic limb-threatening ischemia.

Slow heart rate recovery (HRR) after exercise is a predictor of overall mortality in individuals with and without cardiovascular or respiratory disorders. No data on adults with asthma are available. The purpose of the study is to evaluate the prevalence of slow HRR in these individuals as compared with those with chronic obstructive pulmonary disease (COPD). We performed a retrospective analysis of baseline characteristics and physiological response to the six-minute walking distance test of stable individuals with asthma or COPD. Slow HRR was defined as HRpeak - HR at 1 minute after end exercise <12 bpm. Individuals with asthma walked significantly longer (median (IQR): 455 (385-512) vs 427 (345-485) meters; p=0.005) with a lower prevalence of slow HRR (30.3% vs 49.0%, respectively: p<0.001) than those with COPD. Individuals with asthma and slow HRR were older and walked less than those with normal HRR, without any difference in airway obstruction or in disease severity. Multivariate analysis showed that only the difference HRpeak - baseline HR (∆HR), was a predictor of slow HRR in both groups. More than 30% of adult individuals with asthma may show slow HRR. Only exercise ∆HR but no baseline characteristic seems to predict the occurrence of slow HRR.

Background: Fluid challenge (FC) is often adopted as gold standard used to assess the reliability of passive leg raising (PLR) in predicting fluid responsiveness in the intensive care unit (ICU). This study aimed to address the impact of the different definitions and timings used to assess FC response on PLR reliability., Methods: Ancillary study from a data set of a multicentric study in 85 ICU patient with acute circulatory failure who received a FC (500 mL of crystalloids in 10 minutes) within the first 48h of ICU admission, preceded by PLR in 30 patients. FC response was assessed considering the changes in Cardiac Index (CI) and Stroke Volume Index (SVI) using different thresholds and at different time-points., Results: The definitions of fluid responsiveness by using CI or SVI with a 15% increase after 10 minutes were associated to the best performances of the PLR (AUC 0.94 [95% CI 0.83-1.01] vs. AUC 0.95 [95% CI 0.87-1.02]). The sensitivity of the PLR by adopting the CI or the SVI as reference variable ranged from 54.1% to 67.6% and from 81.5% to 100.0%; the specificity from 65.9% to 78.0% and from 79.5% to 100.0%, respectively. Considering all the subgroups, the number of responders 10 minutes after FC administration was higher as compared to 15 and 30 minutes (140 vs. 120 and 125, respectively, P<0.05)., Conclusions: The reliability of the PLR test to predict fluid responsiveness depends on the definition of FC adopted. The timing of FC outcome assessment affected the overall fluid responsiveness.

Background: The reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis., Methods: An observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests., Results: A total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines., Conclusion: A four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines., Competing Interests: Conflict of interest: S. Aliberti reports grants or contracts from Insmed, Chiesi and Fisher & Paykel; royalties or licences from McGraw Hill; consulting fees from Insmed, Zambon, AstraZeneca, CSL Behring GmbH, Grifols, Fondazione Charta, Boehringer Ingelheim, Chiesi, Zcube Srl and Menarini; and payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from GlaxoSmithKline, and for participation on a Data Safety Monitoring Board or Advisory Board for Insmed and AstraZeneca, all outside the submitted work. M. Mantero declares honoraria for educational events from GlaxoSmithKline and Boehringer Ingelheim, outside the present study. A. Stainer reports grants, speaker fees and travel support from AstraZeneca, Bayer, Chiesi, Forest Laboratories, GlaxoSmithKline, Insmed, Pfizer, Medimmune, Novartis and Zambon, outside the submitted work. E. Polverino reports grants or contracts from Grifols; consulting fees from Insmed, Chiesi and Zambon; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from Insmed, GlaxoSmithKline, Teva, Boehringer Ingelheim, Chiesi and Zambon; support for attending meetings from Insmed and Teva, and for participation on a Data Safety Monitoring Board or Advisory Board from Insmed and Chiesi, all outside the submitted work. J.D. Chalmers reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Insmed, grants from Gilead Sciences, and personal fees from Chiesi, Novartis and Zambon, outside the submitted work. F. Blasi reports grants and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Pfizer and Insmed; grants from Bayer; and personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis and Zambon, outside the submitted work. F. Amati, A. Gramegna, B. Vigone, M. Oriano, G. Sotgiu, E. Simonetta, L. Saderi, S. Tammaro and P. Marchisio report no conflict of interest., (Copyright ©The authors 2022.)

Background: According to the international guidelines, patients affected by interstitial lung disease with unusual clinical presentation and radiological findings that are not classic for usual interstitial pneumonia end up meeting criteria for surgical lung biopsy, preferably performed with video-assisted thoracic surgery. The growing appeal of non-intubated thoracic surgery has shown the benefits in several different procedures, but the strict selection criteria of candidates are often considered a limitation to this approach. Although several authors define obesity as a contraindication for non-intubated thoracoscopic surgery, the assessment of obesity as a dominant risk factor represents a topic of debate when minor tubeless procedures such as lung biopsy are considered. Our study aims to investigate the impact of obesity on morbidity and mortality in non-intubated lung biopsy patients with interstitial lung disease, analyzing the efficacy and safeness of this procedure., Materials and Methods: The study group of 40 obese patients consecutively collected from 202 patients who underwent non-intubated lung biopsy was compared with overweight and normal-weight patients, according to their body mass index. Post-operative complications were identified as the primary endpoint. The other outcomes explored were the early 30-day mortality rate and intraoperative complications, length of surgery, post-operative hospitalization, patient's pain feedback, and diagnostic yield., Results: The overall median age of the patients was 67.4 years (60, 73.5). No 30-day mortality or significant differences in terms of post-operative complications ( P = 0.93) were noted between the groups. The length of the surgery was moderately longer in the group of obese patients ( P = 0.02). The post-operative pain rating scale was comparable among the three groups ( P = 0.45), as well as the post-operative length of stay ( P = 0.96). The diagnosis was achieved in 99% of patients without significant difference between groups ( P = 0.38)., Conclusion: Our analysis showed the safety and efficacy of surgical lung biopsy with a non-intubated approach in patients affected by lung interstitiopathy. In the context of perioperative risk stratification, obesity would not seem to affect the morbidity compared to normal-weight and overweight patients undergoing this kind of diagnostic surgical procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherchi, Ferrari, Guerrera, Grimaldi, Pinna-Susnik, Murenu, Rosboch, Lybéris, Ibba, Balsamo, Saderi, Fois, Ruffini and Sotgiu.)

Background: The COVID-19 pandemic and associated public health measures have had a profound impact on health systems worldwide. The aim of this study was to assess quantitative and qualitative changes in Pediatric Emergency Department (PED) visits in Sardinia, Italy, during the early period of the COVID-19 pandemic., Methods: We retrospectively investigated the number and characteristics of visits to two major Sardinian PEDs, in the periods January-June 2020 and January-June 2019., Results: From January to June 2020, 8399 PED visits with 1160 hospital admissions (13.8% of PED visits) were registered, compared with 15,692 PED visits (Δ = -46.5%) and 1819 hospital admissions (11.6% of PED visits) occurring from January to June 2019. Comparing January-June 2020 with January-June 2019, we found differences in the percentage of visits for age groups, and significant changes in the proportion of triage codes, with a decrease in green codes (72.1% vs 74.2%, respectively) and an increase in white codes (19.0% vs 16.5%, respectively). Moreover, in the period January-June 2020, the frequency of skin disorders and acute respiratory disease significantly decreased, while the frequency of trauma, acute surgical disease, intoxication, and neuropsychiatric disease significantly increased., Conclusions: After the beginning of the Italian lockdown, we observed a marked drop in the number of PED visits, an increase in hospital admission rate, and radical changes in the reason for visit., (© 2022. The Author(s).)

Background: Carbapenem-resistant Klebsiella pneumoniae (CR-Kp) is endemic globally, causing severe infections in hospitalized patients. Surveillance programs help monitor and promptly identify the emergence of new clones. We reported the rapid spread of a novel clone of K. pneumoniae co-harbouring class A and D carbapenemases in colonized patients, and the potential risk factors involved in the development of infections. Methods: Rectal swabs were used for microbiological analyses and detection of the most common carbapenemase encoding genes by real-time PCR (i.e., blaKPC, blaOXA-48, blaNDM, blaVIM, and blaIMP). All strains co-harbouring KPC and OXA-48 genes were evaluated. For each patient, the following variables were collected: age, sex, length and ward of stay, device use, and outcome. Clonality of CR-Kp was assessed by preliminary pulsed field gel electrophoresis (PFGE), followed by multi-locus sequence typing (MLST) analyses. Results: A total of 127 isolates of K. pneumoniae co-harbouring KPC and OXA-48 were collected between September 2019 and December 2020. The median age (IQR) of patients was 70 (61-77). More than 40% of patients were admitted to intensive care unit (ICU). Around 25% of patients developed an invasive infection, the majority of which were respiratory tract infections (17/31; 54.8%). ICU stay and invasive infection increased the risk of mortality (OR: 5.39, 95% CI: 2.42-12.00; OR 6.12, 95% CI: 2.55-14.69, respectively; p -value ≤ 0.001). The antibiotic susceptibility test showed a resistance profile for almost all antibiotics considered. Monoclonal origin was confirmed by PFGE and MLST showing a similar restriction pattern and belonging to ST-512. Conclusions: We report the spread and the marked antibiotic resistance profiles of K. pneumoniae strains co-producing KPC and OXA-48. Further study could clarify the roles of clinical and microbiological variables in the development of invasive infection and increasing risk of mortality, in colonized patients.

Early physiotherapy could play an important role in the management of severe COVID-19 subjects with consequences of prolonged ICU stay, although its effectiveness is still unclear. Aim of this study is to describe physiotherapy performed in severe COVID-19 patients and to evaluate its safety and feasibility. Consecutive adults with confirmed SARS-CoV-2 infection, admitted to the ICU, needing invasive mechanical ventilation for >24 hours and receiving early physiotherapy, have been enrolled. Adverse events occurred during physiotherapy sessions and timing and type of physiotherapy delivered were analysed, to identify the interventions most frequently performed and to determine the time taken to first mobilize, stand and walk. Functional and clinical assessment of patients was also performed at hospital discharge. Eighty-four severe COVID-19 subjects were enrolled. Few minor adverse events were recorded. Active mobilization was promoted over passive mobilization and independence in daily life activities was supported. Time interval from patients' intubation to the first physiotherapy treatment was 13 days and to walking was 27 days. Forty-eight (57.1%) subjects returned at home, whereas 29 (34.5%) were discharged to in-patient rehabilitation. Patients with tracheostomy experienced a delay in time from ICU admission until sit out of bed and ambulation, if compared with subjects without tracheostomy, although no differences were found in 6MWT and 1m-STST performances. This study reporting early physiotherapy during pandemic suggests that this intervention is feasible and safe for severe COVID-19 subjects, as well as healthcare workers, although delayed compared to other critically ill patients.

HER2+ breast cancer (BC) is an aggressive subtype representing a genetically and biologically heterogeneous group of tumors resulting in variable prognosis and treatment response to HER2-targeted therapies according to estrogen (ER) and progesterone receptor (PR) expression. The relationship with androgen receptors (AR), a member of the steroid hormone's family, is unwell known in BC. The present study aims to evaluate the prognostic impact of AR expression in HER2+ BC subtypes. A total of 695 BCs were selected and reviewed, AR, ER, PR and HER2 expression in tumor cells were examined by immunohistochemical method, and the SISH method was used in case of HER2 with equivocal immunohistochemical score (2+). A high prevalence of AR expression (91.5%) in BC HER+ was observed, with minimal differences between luminal and non-luminal tumor. According to steroid receptor expression, tumors were classified in four subgroups, including BC luminal and non-luminal HER2+ expressing or not AR. The luminal BC HER2 + AR+ was associated with lower histological grade, lower tumor size, higher PR expression and lower HER2 intensity of expression (2+). Also, the non-luminal tumors AR+ showed lower tumor size and lower prognostic stage but frequently higher grade and higher HER2 intensity of expression (3+). These findings should suggest a different progression of luminal and non-luminal tumors, both expressing AR, and allow us to speculate that the molecular mechanisms of AR, involved in the biology of BC HER2 + AR+, differ in relation to ER and PR expression. Moreover, AR expression may be a useful predictor of prognosis for overall survival (OS) in HER2+ BC subtypes. Our findings suggest that AR expression evaluation in clinical practice could be utilized in clinical oncology to establish different aggressiveness in BC HER2+ subtypes.

The assessment of human papillomavirus (HPV) genotype dynamics could support the adoption of more tailored preventive actions against cervical cancer. The aim of the study was to describe the prevalence of HPV infection, HPV genotype distribution, and the epidemiological characteristics of women with ASC-US cytology since the introduction of HPV-DNA testing in Sardinia (Italy), (March 2016-December 2020). Specimens were tested by RT-PCR for 14 high-risk HPV genotypes. A total of 1186 patients were enrolled, with a median (IQR) age of 41 (38-48) years. Of these women, 48.1% were positive for at least one HPV genotype; 311 (26.2%) women were vaccinated with a median (IQR) age of 38 (30/47) years. The percentage of prevalence of HPV-16, -31, -66, -56, and -51 was 36.3%, 18.7%, 11.9%, 11.4% and 10.7%, respectively. The highest prevalence of infection was found in women aged <41 years, and single women. Moreover, women aged >41 years (OR: 0.51, 95% CI: 0.31-0.86; p -value: 0.01), having parity (OR: 0.57, 95% CI: 0.34-0.96, p -value: 0.04), and higher educational level (OR: 0.39, 95% CI: 0.18-0.87; p -value: 0.02) were associated with a lower CIN2+ risk. We did not find a significant difference in terms of prevalence of HPV-16 infection between vaccinated and non-vaccinated (18.3% vs. 17.1%; p -value < 0.001). Our results support the adoption of nonavalent HPV-vaccine to prevent the most prevalent infections caused by HPV-16 and -31 genotypes and underscore the need of surveillance to implement tailored vaccination programs and preventive strategies.

Background: Over the last decades aggressive interventions have been successful to improve nutritional outcomes in people with cystic fibrosis (CF). As a result, with improvement of life expectancy and new CFTR modulators, overweight and obesity are progressively becoming a source of concern for adult population and in developed countries., Methods: This was a multicenter, observational, cross-sectional study of 321 adults with CF at three large CF centers in Italy. Patients were divided into three groups according to BMI classes, overweight and obesity (OW) group including patients with BMI ≥25 kg/m 2 , normal weight (NW) group with BMI 18.6-24.9 kg/m 2 and underweight (UW) group with BMI ≤18.5 kg/m 2 ., Results: We demonstrated that prevalence of OW in adults with CF in Italy is 22%. OW status is independently associated with male sex (OR 3.520, P = 0.001), pancreatic sufficiency (OR 2.873, P = 0.014) and older age at diagnosis (1.015, P = 0.042). BMI correlated with ppFEV1 (r = 0.337; P<0.0001) with median ppFEV1 significantly higher in patients with OW than comparisons. We also reported preliminary data on unfavorable cardiovascular risk factors in a subgroup of patients, where median blood levels [IQR] of cholesterol and systemic hypertension [%] were significantly higher in the OW group than in the NW and UW., Conclusions: People with CF and OW is a relevant patient group that might deserve better definition and proper clinical management., Competing Interests: Declaration of competing of interest The authors declare no conflict of interest., (Copyright © 2021. Published by Elsevier B.V.)

Background: Patients with asthma usually present airway inflammation classified as eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic pattern according to sputum inflammatory cells., Objective: The aim of the study was to analyze clinical and biological characteristics of patients with asthma and mixed granulocytic pattern in comparison with the other groups., Methods: Induced sputum was used to assess airway inflammation; lung function was evaluated as well as blood leukocytes and disease control. History of comorbidities was collected., Results: We retrospectively analyzed 231 subjects with asthma; patients with mixed granulocytic pattern were more frequently male compared with paucigranulocytic subjects, older than eosinophilic and paucigranulocytic patients with increased number and vitality of sputum cells compared to eosinophilic and paucigranulocytic patients and higher cumulative illness rating score, related to increased age. Smoking history, age of disease onset, and ICS treatment were not associated with higher mixed granulocytic pattern occurrence. Subjects with neutrophilic inflammation (mixed granulocytic and neutrophilic patterns considered altogether) were more frequently obese. In subjects under 67 years of age (median of the enrolled subjects), arterial hypertension was the only comorbidity more frequent in mixed granulocytic than in the other groups. 137/231 subjects were re-valuated during follow-up. Lung function of patients with mixed granulocytic, neutrophilic, and paucigranulocytic patterns improved less than that of eosinophilic patients., Conclusion: Aging and presence of comorbidities, in particular obesity and hypertension, are characteristics of patients with asthma and mixed granulocytic pattern. They could respond less well to treatment than eosinophilic patients., (© 2022 S. Karger AG, Basel.)

The presence of an interatrial block (IAB) on surface ECG should be considered as a hallmark of atrial electrical remodelling. This is often accompanied by morphological abnormalities. We aimed to investigate the frequency of IAB and its relationship with the echocardiographic indices of left atrial (LA) remodelling in patients hospitalised with acute HF. Ninety-four consecutive HF patients underwent 12-lead ECG, transthoracic echocardiogram including a detailed study of the LA, and blood tests (including NT-proBNP) on the same day. Thirty-six patients were excluded from the analysis because of atrial fibrillation or rhythms other than sinus. Twenty-eight over 58 (48%) were males. Median age was 72 (IQR 60-82) years. The majority of patients (72%) were diagnosed as having an HF with reduced ejection fraction. Overall, 27 (46%) patients presented with an advanced III or IV NYHA functional class. Median plasma NT-proBNP was 3046 (IQR 1066-5460) pg/ml. Nearly, all the enrolled patients (90%) showed LA dilation. Nineteen patients (33%) presented with advanced IAB. There was a trend toward a more advanced age in patients with advanced IAB (median age 79 vs 68, p = 0.051). Moreover, they were more frequently treated with anticoagulants (42% vs 13%, p = 0.01), and they exhibited greater LA structural and functional remodelling documented by larger area (28 vs 26 cm 2 , p = 0.04) and greater minimum LA volume index-LAVi (43 ± 16 vs 36 ± 10, p = 0.04). Advanced IAB resulted to be an independent determinant of LA area (Beta 3.49 (0.37-6.60), p = 0.03) and minimum LAVi (Beta 7.22 (0.15-14.30), p = 0.045), and vice versa. LA electrical and structural remodelling is highly prevalent in a non-selected cohort of patients with acute HF. Advanced IAB on surface ECG is present in a high percentage of cases. Patients with advanced IAB tend to be older, and they exhibit higher degrees of LA structural and functional remodelling., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: The role of endoscopic ultrasound with bronchoscope fine-needle aspiration (EUS-B-FNA) in the diagnosis of suspected malignant pulmonary lesions adjacent to the esophagus has been poorly investigated. The aim of the present study was to assess the accuracy of EUS-B-FNA for the diagnosis and molecular profiling of paraesophageal pulmonary lesions, as well as its predictors of success., Materials and Methods: Patients who underwent EUS-B-FNA for the diagnosis of paraesophageal lesions were consecutively enrolled in four Italian centers. Demographic, clinical, procedural, pathological, and molecular characteristics of the malignant samples were collected. The primary outcome was the diagnostic accuracy for pulmonary malignancies. Secondary outcomes were diagnostic yield and predictors of success for diagnosis and molecular profiling., Results: 107 adult patients (60 [56.1%] males; median (interquartile range) age: 69 [60-70] years) were enrolled. The diagnostic accuracy of EUS-B-FNA was 95.3% in the overall cohort and 95.2% in the 99 patients with a final diagnosis of malignancy. Neither clinical nor procedural variables significantly affected the diagnostic accuracy, whereas rapid on-site evaluation (ROSE), performed by pathologists or trained pulmonologists, was a strong predictor for a complete molecular profiling (OR [95% CI]: 12.9 [1.2-137.4]; p value: 0.03)., Conclusion: EUS-B-FNA is a safe and accurate method for the diagnosis of paraesophageal pulmonary lesions. The presence of ROSE is relevant for a complete molecular profiling in this selected cohort of patients with advanced lung cancer., (© 2022 S. Karger AG, Basel.)

Introduction: To analyze the virus spread among Sassari Hospital staff in the first Covid-19 wave and the impact of the Swab Team, a multidisciplinary task force entitled of nasopharyngeal swab collection and testing., Methodology: Nasopharyngeal swabs from HCWs between March 6 and May 28 2020 are evaluated., Results: 4919 SARS-CoV-2 tests were performed on 3521 operators. Nurses and doctors are the categories at highest risk. After the Swab Team institution, the average number of swabs raised from 47/day to 86/day (p = 0.007). Positive samples decreased from 18.6% to 1.7% (p < 0.0001)., Conclusions: The Swab Team is effective in increasing the cases tested and in reducing the reporting time. Procedure standardization reduces the risk for all the subjects involved (no transmission among swab team members, nor during the sample collection)., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2021 Francesco Bussu, Davide Rizzo, Laura Saderi, Antonio Piras, Laura Maria De Luca, Giacomo De Riu, Luigi Angelo Vaira, Antonello Serra, Paola Altrudo, Domenico Delogu, Ignazio Dettori, Francesco Giuseppe Riu, Flavia Angioj, Laura Firino, Rosalba Govoni, Gabriele Ibba, Vincenzo Lai, Erica Mura, Bianca Paglietti, Claudia Piu, Anna Puggioni, Elena Rimini, Giulia Rocca, Caterina Serra, Sergio Uzzau, Salvatore Rubino, Giovanni Sotgiu.)

The best noninvasive respiratory strategy in patients with Coronavirus Disease 2019 (COVID-19) pneumonia is still discussed. We aimed at assessing the rate of endotracheal intubation (ETI) in patients treated with continuous positive airway pressure (CPAP) and noninvasive ventilation (NIV) if CPAP failed. Secondary outcomes were in-hospital mortality and in-hospital length of stay (LOS). A retrospective, observational, multicenter study was conducted in intermediate-high dependency respiratory units of two Italian university hospitals. Consecutive patients with COVID-19 treated with CPAP were enrolled. Thoraco-abdominal asynchrony or hemodynamic instability led to ETI. Patients showing SpO 2 ≤ 94%, respiratory rate ≥ 30 bpm or accessory muscle activation on CPAP received NIV. Respiratory distress and desaturation despite NIV eventually led to ETI. 156 patients were included. The overall rate of ETI was 30%, mortality 18% and median LOS 24 (17-32) days. Among patients that failed CPAP ( n = 63), 28% were intubated, while the remaining 72% received NIV, of which 65% were intubated. Patients intubated after CPAP showed lower baseline PaO 2 /FiO 2 , lower lymphocyte counts and higher D-dimer values compared with patients intubated after CPAP + NIV. Mortality was 22% with CPAP + ETI, and 20% with CPAP + NIV + ETI. In the case of CPAP failure, a NIV trial appears feasible, does not deteriorate respiratory status and may reduce the need for ETI in COVID-19 patients.

EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial. In the present study, we evaluated the role played by EGFR overexpression in CCRCC and its prognostic significance associated with different immunohistochemical localization patterns. In our study, the Total Score (TS) related to membranous-cytoplasmic EGFR expression showed a significant correlation with grade, pathologic stage (pT), and Stage, Size, Grade, and Necrosis (SSIGN) score, and a negative correlation with nuclear EGFR expression. No significant correlations were shown between nuclear EGFR and clinic-pathological features. Additionally, a correlation between SGLT1 expression levels and pT was described. Multivariate analysis identifies pT and SSIGN score as independent prognostic factors for CCRCC. A significantly increased survival rate was found in the case of positive expression of nuclear EGFR and SGLT1. Based on our findings, SGLT1 and nuclear EGFR overexpression defines a subgroup of CCRCC patients with good prognosis. Membranous-cytoplasmic EGFR expression was shown to be a poor prognostic factor and could define a CCRCC subgroup with poor prognosis that should be responsive to anti-EGFR therapies.

Background: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs)., Methods: Observational, prospective, multicentre, Italian study., Results: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence., Conclusions: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding., Trial Registration: NCT02045394., (© 2021. The Author(s).)

Background: TRA is recommended as the preferred approach to perform coronary angiography and PCI. Despite this, TRA-PCI is burdened by a high access site crossover rate. Assisted-tracking techniques (balloon-assisted tracking and pigtail-assisted tracking) have showed to solve some of the issues related with challenging TRA procedures, but few data exist about procedural outcomes. Aim of the study was to evaluate the efficacy and safety of the assisted-tracking (AsTra) techniques during transradial (TRA) percutaneous coronary intervention (PCI)., Methods: From January 2016 to December 2019, 1682 TRA-PCI procedures were performed. Starting from January 2018, AsTra techniques were adopted in 72 cases of challenging TRA-PCI, and clinical data, procedural results and 30 days follow-up data were retrospectively collected. Because not all interventionalists used AsTra techniques, we had the opportunity to evaluate if their utilization influenced TRA-PCI rates. To this purpose, we identified two groups of interventionalists and tested the hypothesis that these techniques could lead to a significant improvement in TRA-PCI rates., Results: Between January 2016 and December 2019, TRA-PCI rates increased from 68.5% to 95%. The TRA-PCI success rate increased significantly for interventionalists who adopted assisted-tracking techniques (p-value < 0.0001 for year 2019; p-value = 0.003 for year 2018)., Conclusions: Assisted-tracking techniques appear to be effective in increasing TRA-PCI rates. Their use is associated with low complication and low access crossover rates., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The management of multidrug-resistant tuberculosis (TB) is associated with low treatment success, high mortality and failure rates. New drugs and novel short-therapeutic regimens have only recently helped overcome these obstacles. We carried out a narrative literature review aimed at summarizing the scientific evidence on the recent therapeutic advances in the field of drug-resistant TB. Experimental and observational studies on novel (i.e. bedaquiline, delamanid, pretomanid) drugs and novel regimens and the main pharmacological characteristics of the newest compounds are described. We also highlight the main scientific evidence on therapeutic strategies complementary to standard chemotherapy (i.e. new approaches to drug delivery, host-directed therapy, surgery, new collapse therapy, rehabilitation, and palliative care)., Competing Interests: Conflict of interest statement Nothing declared., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rationale: Although platelets are considered key inflammatory mediators in respiratory diseases, their role in bronchiectasis has not been fully explored. Objectives: We hypothesized that thrombocytosis in stable state may be associated with bronchiectasis severity and worse clinical outcomes. Methods: Patients with bronchiectasis have been enrolled from 10 centers in Europe and Israel, with platelet count recorded during stable state. The primary outcome was 5-year all-cause mortality. Secondary outcomes included exacerbations, hospitalizations, and mortality at 1, 2, and 3-year follow-up. Analyses were conducted using logistic regression after adjustment for confounding variables. Results: Among the 1,771 patients (median age, 67 yr; 63.4% female) included, 136 (7.7%) had thrombocytosis. Patients with thrombocytosis had a significantly higher disease severity, worse quality of life, higher number of exacerbations and hospitalizations, and higher mortality rate at both 3-year (23 [22.8%] vs. 83 [8.5%], respectively; P  < 0.01) and 5-year (26 [35.1%] vs. 116 [15.9%], respectively; P  < 0.01) in comparison with those with normal platelet count. Thrombocytosis was significantly associated with hospitalizations because of severe exacerbations (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.20-2.79; P  = 0.01) after 1-year follow-up, as well as increased 3-year (OR, 3.06; 95% CI, 1.74-5.39; P  < 0.01) and 5-year (OR, 2.46; 95% CI, 1.39-4.37; P  < 0.01) mortality. Conclusions: Platelets represent a cheap and easy-to-evaluate biomarker, and the presence of thrombocytosis during stable state is associated with disease severity, hospitalizations because of exacerbations, poor quality of life, and mortality in adults with bronchiectasis.

Objective: High prevalences of muscle weakness and impaired physical performance in hospitalized patients recovering from COVID-19-associated pneumonia have been reported. Our objective was to determine whether the level of exercise capacity after discharge would affect long-term functional outcomes in these patients., Methods: From three to five weeks after discharge from acute care hospitals (T0), patients underwent a six-minute walk test (6MWT) and were divided into two groups according to the distance walked in percentage of predicted values: <75% group and ≥75% group. At T0 and three months later (T1), patients completed the Short Physical Performance Battery and the Euro Quality of Life Visual Analogue Scale, and pulmonary function and respiratory muscle function were assessed. In addition, a repeat 6MWT was also performed at T1., Results: At T0, 6MWD values and Short Physical Performance Battery scores were lower in the <75% group than in the ≥75% group. No differences were found in the Euro Quality of Life Visual Analogue Scale scores, pulmonary function variables, respiratory muscle function variables, length of hospital stay, or previous treatment. At T1, both groups improved their exercise capacity, but only the subjects in the <75% group showed significant improvements in dyspnea and lower extremity function. Exercise capacity and functional status values returned to predicted values in all of the patients in both groups., Conclusions: Four weeks after discharge, COVID-19 survivors with exercise limitation showed no significant differences in physiological or clinical characteristics or in perceived health status when compared with patients without exercise limitation. Three months later, those patients recovered their exercise capacity.

Background: Postoperative complications impact on early and long-term patients' outcome. Appropriate perioperative fluid management is pivotal in this context; however, the most effective perioperative fluid management is still unclear. The enhanced recovery after surgery pathways recommend a perioperative zero-balance, whereas recent findings suggest a more liberal approach could be beneficial. We conducted this trial to address the impact of restrictive vs. liberal fluid approaches on overall postoperative complications and mortality., Methods: Systematic review and meta-analysis, including randomised controlled trials (RCTs). We performed a systematic literature search using MEDLINE (via Ovid), EMBASE (via Ovid) and the Cochrane Controlled Clinical trials register databases, published from 1 January 2000 to 31 December 2019. We included RCTs enrolling adult patients undergoing elective abdominal surgery and comparing the use of restrictive/liberal approaches enrolling at least 15 patients in each subgroup. Studies involving cardiac, non-elective surgery, paediatric or obstetric surgeries were excluded., Results: After full-text examination, the metanalysis finally included 18 studies and 5567 patients randomised to restrictive (2786 patients; 50.0%) or liberal approaches (2780 patients; 50.0%). We found no difference in the occurrence of severe postoperative complications between restrictive and liberal subgroups [risk difference (95% CI) = 0.009 (- 0.02; 0.04); p value = 0.62; I 2 (95% CI) = 38.6% (0-66.9%)]. This result was confirmed also in the subgroup of five studies having a low overall risk of bias. The liberal approach was associated with lower overall renal major events, as compared to the restrictive [risk difference (95% CI) = 0.06 (0.02-0.09); p value  = 0.001]. We found no difference in either early (p value  = 0.33) or late (p value  = 0.22) postoperative mortality between restrictive and liberal subgroups CONCLUSIONS: In major abdominal elective surgery perioperative, the choice between liberal or restrictive approach did not affect overall major postoperative complications or mortality. In a subgroup analysis, a liberal as compared to a restrictive perioperative fluid policy was associated with lower overall complication renal major events, as compared to the restrictive., Trial Registration: CRD42020218059; Registration: February 2020, https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=218059 .

A multicenter, nonrandomized, prospective, controlled study was conducted to evaluate, as perioperative prophylactic treatment, the anti-infective effectiveness of 0.66% povidone-iodine eye drops (IODIM ® ) against the bacterial flora of the conjunctival surface of patients who undergo cataract surgery. Eye drops containing 0.66% povidone-iodine were applied to the eye undergoing cataract surgery; the untreated contralateral eye was used as control. One hundred and twenty patients set to receive unilateral cataract surgery were enrolled in 5 Italian Ophthalmology Centers and pretreated for three days with 0.66% povidone-iodine eye drops. The contralateral eye, used as control, was left untreated. Conjunctival swabs of both eyes were collected at the baseline visit and after three days of treatment, just before the cataract surgery. A qualitative and quantitative microbiological analysis of bacterial presence was evaluated by means of bacterial culture, followed by identification. Methicillin resistance determination was also performed on staphylococci isolates. Bacterial load before and after treatment of the eye candidate for cataract surgery was evaluated and compared to the untreated eye. A reduction or no regrowth on the culture media of the bacterial load was observed in 100% of the study subjects. A great heterogenicity of bacterial species was found. The 0.66% povidone-iodine eye drops, used for three days prior to cataract surgery, were effective in reducing the conjunctival bacterial load. The 0.66% povidone-iodine eye drops (IODIM ® ) might represent a valid perioperative prophylactic antiseptic adjuvant treatment to protect the ocular surface from microbial contamination in preparation of the surgical procedure.

Introduction: to assess incidence, prognosis and obstetric outcome of patients treated for gestational trophoblastic disease GTD in a twenty-year period. Incidence, prognosis and obstetric outcome of gestational throphoblastic disease., Methods: retrospective study., Results: Fifty-four cases of GTD: 46 (85.18%) cases of Hydatidiform mole (HM); 8 cases of Persistent Gestational Trophoblastic Neoplasia (GTN) (14.81%): 6/8 cases (75%) GTN not metastatic; 2/8 cases (25%) GTN metastatic. In both cases, the metastases occurred in the lungs. In 3 out of 8 GTN cases (37.5%) a histological picture of choriocarcinoma emerged. The incidence of GTD cases treated from 2000 to 2020 was 1.8 cases per 1000 deliveries and 1.3 cases per 1000 pregnancies. Of the 54 patients, 30 (55.56%) presented showed normal serum hCG levels without the need for chemotherapy. On the other hand, 24 patients (44.44%) developed a persistent trophoblastic disease and underwent adjuvant therapy. The negative prognostic factors that affected the risk of persistence of GTD were: serum hCG levels at diagnosis > 100,000 mUI/ml; characteristic " snow storm " finding at the ultrasound diagnosis; a slow regression of serum hCG levels during follow-up; the persistence of high serum hCG levels (especially if > 1000 mUI/ml one month after suction curettage) that was the main risk factor for resistance to first-line chemotherapy. There were 10 pregnancies in total following treatment. Patients' survival in our study was 100%., Discussion: Although GTD is a rare disease, its incidence was 1.3 cases per 1,000 pregnancies in Sardinia, Italy, higher if compared with mean national and worldwide incidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Capobianco, Tinacci, Saderi, Dessole, Petrillo, Madonia, Virdis, Olivari, Santeufemia, Cossu, Dessole, Sotgiu and Cherchi.)

The scientific debate on the criteria guiding hospitalization of tuberculosis (TB) and COVID-19 patients is ongoing. The aim of this review is to present the available evidence on admission for TB and TB/COVID-19 patients and discuss the criteria guiding hospitalization. Furthermore, recommendations are made as derived from recently published World Health Organization documents, based on Global Tuberculosis Network (GTN) expert opinion. The core published documents and guidelines on the topic have been reviewed. The proportion of new TB cases admitted to hospital ranges between 50% and 100% while for multidrug-resistant (MDR) TB patients it ranges between 85 and 100% globally. For TB patients with COVID-19 the proportion of cases admitted is 58%, probably reflecting different scenarios related to the diagnosis of COVID-19 before, after or at the same time of the active TB episode. The hospital length of stay for drug-susceptible TB ranges from 20 to 60 days in most of countries, ranging from a mean of 10 days (USA) to around 90 days in the Russian Federation. Hospitalization is longer for MDR-TB (50-180 days). The most frequently stated reasons for recommending hospital admission include: severe TB, infection control concerns, co-morbidities and drug adverse events which cannot be managed at out-patient level. The review also provides suggestions on hospital requirements for safe admissions as well as patient discharge criteria, while underlining the relevance of patient-centred care through community/home-based care., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Complicated parapneumonic effusions and empyema represent advanced stages of pleural infections and are characterized by a high mortality. Medical thoracoscopy is a safe and minimally invasive endoscopic technique prescribed to treat severe pleural infections. However, only a few studies evaluated its success rate. A systematic review of observational studies was performed to assess the efficacy of medical thoracoscopy in patients with complicated parapneumonic effusions and empyema, as well as its predictive factors., Methods: A search of the scientific evidence was carried out using PubMed, EMBASE, and Cochrane Central Register of Controlled Trials. Articles describing observational studies on medical thoracoscopy in patients with parapneumonic effusions and empyema were selected., Results: Eight studies met the inclusion criteria. The pooled treatment success rate of thoracoscopy was 85% (95% CI 80.0-90.0%; I 2 : 61.8%) when used as first-line intervention or after failure of chest tube. The pooled complication rate was 9.0% (95% CI 6.0-14.0%; I 2 : 58.8%). A pooled difference of treatment success of 9.0% (95% CI 1.0-18.0%) was found when post-thoracoscopy intra-pleural fibrinolysis was prescribed. Pooled success rate was higher in cases with pleural fluid culture negativity (pooled difference: 14.0%; 95% CI 4.0-24.0%)., Conclusions: Medical thoracoscopy is effective and safe when prescribed for complicated parapneumonic effusions and empyema. Bacteriological negativity of pleural effusion specimens and administration of adjuvant intra-pleural fibrinolysis after the procedure are associated with a higher success rate.

Background: Tuberculosis (TB) unevenly affects individuals across the globe, especially in rural areas of low-income countries. Aim of the study was to assess the impact of social protection to increase TB awareness on treatment outcomes among TB patients in a rural area of Senegal. Materials & methods: The study, conducted in Fimela district (Senegal) from 1 January 2010 to 31 December 2019 and the intervention started from 31 January 2013, includes activities to increase awareness, active case finding, active follow-up and social protection. Results: Overall, 435 subjects - mainly male and young - were included in the analysis. Among TB cases, 94% had pulmonary involvement, 87% had no previous TB history, and 6% resulted positive HIV. Improved outcome was observed once intervention began (from 71 to 91%, p < 0.001); whereas mortality decreased (from 15 to 5%; p < 0.001), especially for those HIV co-infected for whom TB mortality rate dropped from 70 to 29%. Conclusion: After beginning the cooperation program, TB treatment success increased as a result of the decline of mortality, especially in people living with HIV.

Non-pharmacological interventions and tracing-testing strategy proved insufficient to reduce SARS-CoV-2 spreading worldwide. Several vaccines with different mechanisms of action are currently under development. This review describes the potential target antigens evaluated for SARS-CoV-2 vaccine in the context of both conventional and next-generation platforms. We reported experimental data from phase-3 trials with a focus on different definitions of efficacy as well as factors affecting real-life effectiveness of SARS-CoV-2 vaccination, including logistical issues associated to vaccine availability, delivery, and immunization strategies. On this background, new variants of SARS-CoV-2 are discussed. We also provided a critical view on vaccination in special populations at higher risk of infection or severe disease as elderly people, pregnant women and immunocompromised patients. A final paragraph addresses safety on the light of the unprecedented reduction of length of the vaccine development process and faster authorization., (Copyright © 2021. Published by Elsevier Ltd.)

Background: The fluid challenge response in surgical patients can be predicted by functional haemodynamic tests. Two tests, the mini-fluid challenge (mini-FC) and end-expiratory occlusion test (EEOT), have been assessed in a few small single-centre studies with conflicting results. In general, functional haemodynamic tests have not performed reliably in predicting fluid responsiveness in patients undergoing laparotomy., Objective: This trial is designed to address and compare the reliability of the EEOT and the mini-FC in predicting fluid responsiveness during laparotomy., Design: Prospective, multicentre study., Setting: Three university hospitals in Italy., Patients: A total of 103 adults patients scheduled for elective laparotomy with invasive arterial monitoring., Interventions: The study protocol evaluated the changes in the stroke volume index (SVI) 20 s (EEOT20) and 30 s (EEOT30) after an expiratory hold and after a mini-FC of 100 ml over 1 min. Fluid responsiveness required an increase in SVI at least 10% following 4 ml kg-1 of Ringer's solution fluid challenge infused over 10 min., Main Outcome Measurements: Haemodynamic data, including SVI, were obtained from pulse contour analysis. The area under the receiver operating characteristic curves of the tests were compared with assess fluid responsiveness., Results: Fluid challenge administration induced an increase in SVI at least 10% in 51.5% of patients. The rate of fluid responsiveness was comparable among the three participant centres (P = 0.10). The area under the receiver operating characteristic curves (95% CI) of the changes in SVI after mini-FC was 0.95 (0.88 to 0.98), sensitivity 98.0% (89.5 to 99.6) and specificity 86.8% (75.1 to 93.4) for a cut-off value of 4% of increase in SVI. This was higher than the SVI changes after EEOT20, 0.67 (0.57 to 0.76) and after EEOT30, 0.73 (0.63 to 0.81)., Conclusion: In patients undergoing laparotomy the mini-FC reliably predicted fluid responsiveness with high-sensitivity and specificity. The EEOT showed poor discriminative value and cannot be recommended for assessment of fluid responsiveness in this surgical setting., Trial Registration: NCT03808753., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: HCV infection among vulnerable populations is currently a major issue for HCV elimination program. Incarcerated people and people who inject drugs (PWIDs) are key population groups potentially at high risk for HCV infection. Our aim was to evaluate an extended program of screening, staging and treatment in Italian prison settings., Methods: Patients from eight prisons in five different Italian Regions were enrolled. HCV saliva test (QuickOral Test®) was offered. Data on infection awareness and illicit drug use were also collected. Positive patients underwent early HCV RNA evaluation, staging and prescription on DAAs treatment. The definition of PWID was based on self-reported injecting drug use extracted from medical records (injecting drug use during the previous six months)., Results: A total of 2,376 out of 2,687 individuals (88%) was tested. The median (IQR) age was 42 (32-50) years. PWIDs were 537out of 2,376 (23%). Prevalence of HCV antibodies was 10.4% (248/2,376). PWIDs had a lower awareness of their HCV-Ab positivity than non-PWIDs (p-value <0.001). Furthermore, PWIDs were less likely to be previously treated than non-PWIDs (78% vs 96%, p-value= 0.017). Active infection was found in 41% of patients (101/248). Overall, 61% HCV-positive were PWIDs, with 44% HCV RNA positive. HCV therapy was prescribed to 83% (84/101) of patients with active HCV infection and 67% of these (56/84) were PWIDs. Prescription for HCV treatment in PWIDs accounted for 84% (56/67) (while for non-PWIDs was 82% (28/34) p-value: 0.88. Seventeen patients were referred to a Specialist in other prisons because they were going to be transferred soon to another prison. EOT, as well as SVR12 were achieved in 98% (82/84) treated patients., Conclusions: Among patients, PWIDs had a lower awareness of their HCV-Ab positivity and had previously received less treatments. Saliva test allowed to achieve a more rapid result, stage, and treatment approach. More than 80% of patients underwent treatment, without differences between PWIDs and non-PWIDs. Linkage to care during prison transfer allowed to avoid unplanned interruptions and offered more chances to reach the end of treatment., Competing Interests: Declarations of Interest The authors have no conflict of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Myxomatous mitral valve disease (MMVD) is the most common cardiac disease in dogs. It varies from dogs without clinical signs to those developing left-sided congestive heart failure, leading to death. Cavalier King Charles Spaniels (CKCSs) are particularly susceptible to MMVD. We hypothesised that within the elderly CKCS population, there is a sub-cohort of MMVD-affected dogs that do not have cardiac remodelling. The objectives of the present study were (i) to determine the prevalence and the degree of cardiac remodelling associated with MMVD; and (ii) assess the effect of age, gender, and body weight on echocardiographic status in a population of aged CKCSs. A total of 126 CKCSs ≥ 8 years old were prospectively included. They all had a physical and echocardiographic examination. A systolic murmur was detected in 89% of dogs; the presence of clinical signs was reported in 19% of them; and echocardiographic evidence of MMVD was described in 100%. Despite the high prevalence, 44.4% of the dogs were clear of echocardiographic signs of cardiac remodelling. Age was significantly associated with the presence and severity of cardiac remodelling and mitral valve prolapse. Our results showed that a proportion of elderly CKCS with confirmed MMVD did not undergo advanced stages of this pathology.

Prematurity is the leading cause of neonatal deaths and high economic costs; it depends on numerous biological and social factors, and is highly prevalent in males. Several factors can affect the metabolome of premature infants. Accordingly, the aim of the present study was to analyze the role played by gestational age (GA), parenteral nutrition (PN), and caffeine treatment in sex-related differences of blood metabolome of premature neonates through a MS/MS-based targeted metabolomic approach for the detection of amino acids and acylcarnitines in dried blood spots. GA affected the blood metabolome of premature neonates: male and female very premature infants (VPI) diverged in amino acids but not in acylcarnitines, whereas the opposite was observed in moderate or late preterm infants (MLPI). Moreover, an important reduction of metabolites was observed in female VPI fed with PN, suggesting that PN might not satisfy an infant's nutritional needs. Caffeine showed the highest significant impact on metabolite levels of male MLPI. This study proves the presence of a sex-dependent metabolome in premature infants, which is affected by GA and pharmacological treatment (e.g., caffeine). Furthermore, it describes an integrated relationship among several features of physiology and health.

Low CD4+ cell count in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection during combination antiretroviral therapy (cART) has been described; however, notably few studies have investigated coinfected patients positive for antibodies to the HBV c antigen (HBcAb). An observational retrospective study enrolling 190 patients was conducted by grouping patients with respect to HBV status and recording CD4+ T cell counts and percentages (CD4%), CD8+ T cell counts and percentages (CD8%), and the CD4+ to CD8+ T cell ratio (CD4/CD8) at the time of HIV diagnosis, at the start of treatment and at months 1, 2, 3, 4, 5, 6, 12, and 24 after beginning cART. One hundred and twenty patients (63.2%) were negative for previous HBV infection, while 70 (36.8%) were HBcAb-positive. A significant increase in the CD4/CD8 ratio was recorded in HIV monoinfected subjects compared to HBV coinfected patients from months 4 to 12 from the beginning of cART (p value = 0.02 at month 4, p value = 0.005 at month 5, p value = 0.006 at month 6, and p value = 0.008 at month 12). A significant increase in the absolute count of CD8+ T lymphocytes was described from months 2 to 24 from the start of cART in the subgroup of HBV coinfected patients with an AIDS event at the onset of HIV infection. The presence of HBcAb was observed to be associated with reduced CD4/CD8 ratio growth and a significantly higher proportion of subjects with CD4/CD8 < 0.45 in the HIV/HBV coinfected group. A significant increase in the CD8 T cell count was shown up to 24 months after the initiation of effective cART in the subgroup of patients with the worst immune status.

Background: Appropriate perioperative fluid management is of pivotal importance to reduce postoperative complications, which impact on early and long-term patient outcome. The so-called perioperative goal-directed therapy (GDT) approach aims at customizing perioperative fluid management on the individual patients' hemodynamic response. Whether or not the overall amount of perioperative volume infused in the context of GDT could influence postoperative surgical outcomes is unclear., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the efficacy of GDT approach between study population and control group in reducing postoperative complications and perioperative mortality, using MEDLINE, EMBASE and the Cochrane Controlled Clinical trials register. The enrolled studies were grouped considering the amount infused intraoperatively and during the first 24 h after the admission in the critical care unit (perioperative fluid)., Results: The metanalysis included 21 RCTs enrolling 2729 patients with a median amount of perioperative fluid infusion of 4500 ml. In the studies reporting an overall amount below or above this threshold, the differences in postoperative complications were not statically significant between controls and GDT subgroup [43.4% vs. 34.2%, p value = 0.23 and 54.8% vs. 39.8%; p value = 0.09, respectively]. Overall, GDT reduced the overall rate of postoperative complications, as compared to controls [pooled risk difference (95% CI) = - 0.10 (- 0.14, - 0.07); Chi 2  = 30.97; p value < 0.0001], but not to a reduction of perioperative mortality [pooled risk difference (95%CI) = - 0.016 (- 0.0334; 0.0014); p value = 0.07]. Considering the rate of organ-related postoperative events, GDT did not reduce neither renal (p value = 0.52) nor cardiovascular (p value = 0.86) or pulmonary (p value = 0.14) or neurological (p value = 0.44) or infective (p value = 0.12) complications., Conclusions: Irrespectively to the amount of perioperative fluid administered, GDT strategy reduces postoperative complications, but not perioperative mortality., Trial Registration: CRD42020168866; Registration: February 2020 https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=168866.

Even if major improvements in therapeutic regimens and treatment outcomes have been progressively achieved, tuberculosis (TB) remains the leading cause of death from a single infectious microorganism. To improve TB treatment success as well as patients' quality of life, drug-drug-interactions (DDIs) need to be wisely managed. Comprehensive knowledge of anti-TB drugs, pharmacokinetics and pharmacodynamic (PK/PD) parameters, potential patients' changes in absorption and distribution, possible side effects and interactions, is mandatory to built effective anti-TB regimens. Optimization of treatments and adherence to international guidelines can help bend the curve of TB-related mortality and, ultimately, decrease the likelihood of treatment failure and drop-out during anti-TB treatment. Aim of this paper is to describe the most relevant DDIs between anti-TB and other drugs used in daily clinical practice, providing an updated and "easy-to-use" guide to minimize adverse effects, drop-outs and, in the long run, increase treatment success., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Background : Pulmonary Rehabilitation (PR) is a multimodal treatment that is still poorly investigated in severe asthma where respiratory symptoms remain "uncontrolled" despite intensive pharmacological therapy. Bronchiectasis and obstructive sleep apnea (OSAS) are common comorbidities which may worsen asthma control. Aim: Aim of the present study is to investigate the effectiveness of PR on functional exercise, dyspnea, and muscle fatigue in patients with severe asthma. Methods : A total of 317 patients affected from severe asthma according to GINA guidelines who underwent a multidisciplinary 3 weeks rehabilitation program with an adherence of >80% to PR and able to complete a Six Minute Walking Test (6MWT) were retrospectively included in the analysis. Pulmonary rehabilitation included endurance training, educational meetings, chest physiotherapy, breathing exercises, and psychological support. Six-minute walking distance and Borg scale for dyspnea and muscle fatigue were recorded before and after the rehabilitation. Results : A total of 371 patients were analyzed, 39 had bronchiectasis (10.5%), 163 (43.9%) OSAS and 17 had both (4.6%). PR significantly improved 6MWT distance, Borg dyspnea and muscle fatigue ( p value < 0.0001 for all outcomes) and mean SpO2 recorded during 6MWT ( p value < 0.0001). Median (IQR) delta 6 minute walking distance was 33 (14-60) m. 6MWT distance ( p  < 0.0001) and the oxygen saturation ( p  < 0.01) significantly improved in severe asthma with bronchiectasis and/or OSAS. Conclusions : Our study provides evidence for the first time on a large sample of patients with severe asthma that a multidisciplinary PR program is effective in terms of exercise capacity and symptoms. In addition, exercise capacity improved in the presence of bronchiectasis and/or OSAS.

Background: Systemic hypertension (SH) is a persistent and pathological increase in arterial blood pressure (BP). Chronic SH leads to an increase in aortic (Ao) stiffness, and measuring Ao elasticity is useful for estimating Ao stiffness in humans. Currently, no literature in veterinary medicine describes noninvasive assessment of abdominal Ao elasticity in dogs with SH., Objective: Compare ultrasonographic-derived abdominal Ao strain (AoSt) between hypertensive (HT) and normotensive (NT) dogs., Animals: Fifty privately-owned dogs with clinical signs, conditions, or both potentially associated with SH., Methods: Prospective observational case-control study. Aortic stiffness was estimated by calculating AoSt as follows: AoSt = ([AoDs - AoDd]/AoDd) × 100, where AoDs and AoDd are the Ao diameter in systole and in diastole, respectively. Aortic stiffness was calculated from 2 different Ao transverse sections, the first caudal to the left renal artery (K&#95;AoSt), and the second cranial to the external iliac arteries (I&#95;AoSt)., Results: Thirty-two dogs were included in the HT group and 18 in the NT group. Both K&#95;AoSt and I&#95;AoSt in HT dogs were significantly lower (P < .05) than in NT dogs (7.4 ± SD 3.6) vs 10.3 (±3.8) and 5.7 (interquartile range [IQR], 3.9-7.5) vs 8.1 (IQR, 7-10.3), respectively. Only K&#95;AoSt was significantly influenced by age., Conclusions and Clinical Importance: Ultrasonographic Ao elasticity assessment was feasible to compare HT and NT dogs. Results indicated that K&#95;AoSt and I&#95;AoSt indices can be used to assess SH-related Ao stiffness, especially when indirect BP measurements are inconsistent or inaccurate. Additional studies to assess the AoSt in healthy dogs of various ages are needed., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Background: Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases., Methods: An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression., Results: HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives., Discussion: The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins., Conclusion: HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques.

Introduction: Neutrophilic inflammation is a major driver of bronchiectasis pathophysiology, and neutrophil elastase activity is the most promising biomarker evaluated in sputum to date. How active neutrophil elastase correlates with the lung microbiome in bronchiectasis is still unexplored. We aimed to understand whether active neutrophil elastase is associated with low microbial diversity and distinct microbiome characteristics., Methods: An observational, cross-sectional study was conducted at the bronchiectasis programme of the Policlinico Hospital in Milan, Italy, where adults with bronchiectasis were enrolled between March 2017 and March 2019. Active neutrophil elastase was measured on sputum collected during stable state, microbiota analysed through 16S rRNA gene sequencing, molecular assessment of respiratory pathogens carried out through real-time PCR and clinical data collected., Results: Among 185 patients enrolled, decreasing α-diversity, evaluated through the Shannon entropy (ρ -0.37, p<0.00001) and Pielou's evenness (ρ -0.36, p<0.00001) and richness (ρ -0.33, p<0.00001), was significantly correlated with increasing elastase. A significant difference in median levels of Shannon entropy as detected between patients with neutrophil elastase ≥20 µg·mL -1 (median 3.82, interquartile range 2.20-4.96) versus neutrophil elastase <20 µg·mL -1 (4.88, 3.68-5.80; p<0.0001). A distinct microbiome was found in these two groups, mainly characterised by enrichment with Pseudomonas in the high-elastase group and with Streptococcus in the low-elastase group. Further confirmation of the association of Pseudomonas aeruginosa with elevated active neutrophil elastase was found based on standard culture and targeted real-time PCR., Conclusions: High levels of active neutrophil elastase are associated to low microbiome diversity and specifically to P. aeruginosa infection., Competing Interests: Conflict of interest: M. Oriano has nothing to disclose. Conflict of interest: A. Gramegna has nothing to disclose. Conflict of interest: L. Terranova has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: I. Sulaiman has nothing to disclose. Conflict of interest: L. Ruggiero has nothing to disclose. Conflict of interest: L. Saderi has nothing to disclose. Conflict of interest: B. Wu has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Insmed, AstraZeneca and Boehringer Ingelheim, personal fees from Zambon, grants from Gilead and Grifols, outside the submitted work. Conflict of interest: L.N. Segal reports personal fees for consultancy from Beyond Air, grants from NIH, outside the submitted work. Conflict of interest: P. Marchisio has nothing to disclose. Conflict of interest: F. Blasi reports grants and personal fees from AstraZeneca, Chiesi, GSK, Insmed and Pfizer, grants from Bayer, personal fees from Guidotti, Grifols, Menarini, Mundipharma, Novartis and Zambon, outside the submitted work. Conflict of interest: S. Aliberti reports grants and personal fees from Bayer Healthcare, Aradigm Corporation, Grifols, Chiesi and INSMED, personal fees from AstraZeneca, Basilea, Zambon, Novartis, Raptor, Actavis UK Ltd and Horizon, outside the submitted work., (Copyright ©ERS 2020.)