The current practice in the diagnostic work-up of patients with hemoptysis of unknown etiology: an international survey.

BACKGROUND: Hemoptysis is a challenging and potentially life-threatening medical condition. The most appropriate diagnostic work-up is debated and several diagnostic approaches are implemented worldwide. METHODS: An international, online survey was carried out to investigate the current practice of the diagnostic work-up of patients with hemoptysis of unknown etiology. RESULTS: overall, 604 physicians responded to the survey. At baseline, chest X-ray was suggested as the first diagnostic investigation by 342 (56.6%) participants. Computed tomography (CT) was suggested in each patient with non- and life-threatening hemoptysis by 310 (51.3%) and 526 (87.1%) respondents, respectively. Contrast-enhanced CT is the currently preferred technique (333, 55.1%). In case of patchy ground glass opacities and negative CT, 287 (47.5%) and 222 (36.8%) participants, respectively, would always offer bronchoscopy. Otorhinolaryngological evaluation was mostly suggested in case of suspected upper airways bleeding before other investigations (212, 35.1%). A follow-up was recommended for idiopathic hemoptysis by the majority of the participants (316, 52.3%). A multidisciplinary assessment is deemed crucial for each patient with life-threatening hemoptysis (437, 72.4%). CONCLUSIONS: Chest X-ray and contrast-enhanced CT are currently preferred as the first diagnostic investigations, regardless of hemoptysis severity. Bronchoscopy is suggested in case of negative radiological examination and when CT shows only ground glass opacities. Otorhinolaryngological evaluation is advised before any other investigations when upper airways bleeding is suspected. Patients with idiopathic hemoptysis are suggested to undergo a clinical follow-up and in case of life-threatening bleeding a multidisciplinary assessment is deemed crucial. Due to the heterogeneous approaches a consensus statement would be needed.

Monitoring COPD patients: systemic and bronchial eosinophilic inflammation in a 2-year follow-up.

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.

Copper-Decorated Titanium Electrodes: Impact of Surface Modifications of Substrate on the Morphology and Electrochemical Performance.

This study investigates the effect of surface modifications of the titanium substrate on the growth of electrochemically deposited copper. These materials are intended to serve as cathodes in the electroreduction of nitrates in aqueous solutions. Surface modifications included the use of hydrogen fluoride for titanium etching and anodization to promote the growth of a structured titania nanotube array. The effect of an intermediate calcination step for the nanotubes before deposition was assessed along with a comparison to an untreated substrate electrode. The materials were comprehensively characterized by SEM, XRD, contact angle, potentiodynamic tests, EIS, and cyclic voltammetry. Their electrocatalytic ability was tested in the reduction of aqueous solutions containing nitrates. The results reveal that surface finishing impacted the shape and size of the Cu microparticles, as well as the nucleation mechanism enabling a crystal-facet-controllable synthesis. All the materials exhibited microsized copper particles with a spherical shape with some clusters. On the etched titanium surface, a high number of heterogeneous submicroscopic particles were also present. The thermally treated anodized substrate promoted the development of a combination of sparse microparticles corresponding to defect sites in amorphous titanium and the presence of a diffuse coating of octahedral nanosized particles whose growth was promoted by the tetragonal structure of anatase crystals. Electrochemical tests display reduced charge transfer resistance upon copper deposition on the modified substrates, which is indicative of the enhanced conductivity of the coated materials. Additionally, cyclic voltammetry and electrolysis experiments reveal the electrodes' potential for nitrate reduction, showing a better response for the etched titanium substrate (30% nitrate removal, after 2 h at 25 mA cm-2).

Lung (extracorporeal CO2 removal) and renal (continuous renal replacement therapy) support: the role of ultraprotective strategy in Covid 19 and non-Covid 19 ARDS. A case-control study.

BACKGROUND: Preliminary studies suggest that moderate ARDS and acute renal failure might benefit from extracorporeal CO2 removal (ECCO2R) coupled with CRRT. However, evidence is limited and potential for this coupled treatment may need to be explored. The aim of the present study was to evaluate whether a protective driving pressure was obtained applying low-flow ECCO2-R plus CRRT in patients affected by moderate ARDS with COVID-19 compared to an historical group without COVID-19. METHODS: A case-control study has been conducted comparing a group of consecutive moderate ARDS patients presenting AKI and affected by COVID-19, who needed low-flow ECCO2-R plus CRRT to achieve an ultra-protective ventilatory strategy, with historical group without COVID-19 that matched for clinical presentation and underwent the same ultra-protective treatment. VT was set at 6 mL/kg predicted body weight then ECCO2R was assessed to facilitate ultra-protective low VT ventilation to preserve safe Pplat and low driving pressure. RESULTS: ECCO2R+CRRT reduced the driving pressure from 17 (14-18) to 11.5 (10-15) cmH2O (p<0.0004) in the fourteen ARDS patients by decreasing VT from 6.7 ml/kg PBW (6.1-6.9) to 5.1 (4.2-5.6) after 1 hour (p <0.0001). In the ARDS patients with COVID-19, the driving pressure reduction was more effective from baseline 18 (14-24) cmH2O to 11 (10-15) cmH2O (p<0.004), compared to the control group from 15 (13-17) to 12(10-16) cmH2O (p< 0.03), after one hour. ECCO2R+CRRT did not affected 28 days mortality in the two groups, while we observed a shorter duration of mechanical ventilation (19 {7-29} vs 24 {22-38} days; p=0.24) and ICU length of stay (19 {7-29} vs 24 {22-78} days; p=0.25) in moderate ARDS patients with COVID-19 compared to control group. CONCLUSIONS: In moderate ARDS patients with or without COVID-19 disease, ECCO2R+CRRT may be and effective supportive treatment to reach protective values of driving pressure unless severe oxygenation defects arise requiring ECMO therapy initiation.

Association between patient activation and delayed discharge in elective laparoscopic cholecystectomy: A prospective cohort analysis.

BACKGROUND: Improving patient activation may be an effective way to reduce healthcare costs and improve patient outcomes after surgery. OBJECTIVE: To determine whether preoperative patient activation is associated with delayed discharge (i.e., length of stay >24 h) after elective laparoscopic cholecystectomy. Postoperative symptoms, unscheduled access to healthcare facilities within seven days of surgery, unplanned hospital readmissions, and postoperative complications were analyzed as secondary outcomes. DESIGN: This cohort study was a secondary analysis of the DeDiLaCo study (Delayed Discharge after day-surgery Laparoscopic Cholecystectomy) collecting data of patients undergoing elective laparoscopic cholecystectomy during 2021 in Italy. Data was analyzed from June 2022 to April 2023. SETTING: 90 Italian surgical centers participating in the study. PARTICIPANTS: 4708 adult patients with an instrumental diagnosis of gallbladder disease and undergoing laparoscopic cholecystectomy. Patient activation was assessed using the Italian translation of Patient Activation Measure in the preoperative setting. RESULTS: Of 4532 cases analyzed the median (IQR) Patient Activation Measure score was 80.3 (71.2-92.3). Participants were on average 55.5 years of age and 58.1 % were female. Two groups based on the activation level were created: 270 (6 %) had low activation, and 4262 had high activation. The low activation level was associated with the likelihood of delayed discharge (odds ratio [OR] 1.47, 95 % CI, 1.11-1.95; P = .008), higher symptom burden (OR 1.99, 95 % CI 1.49-2.66, P < .0001), and unplanned healthcare utilization within seven days after hospital discharge (OR 1.85, 95 % CI, 1.29-2.63; P = .001). There was no difference between the high and low activation groups in the incidence of postoperative complications (OR 1.28, 95 % CI, 0.95-1.73; P = .10) and hospital readmission after discharge (OR 0.95, 95 % CI, 0.30-3.05; P = .93). CONCLUSIONS: Our results suggest that patients with low activation have 1.47 times the risk of delayed discharge compared with patients with higher activation, almost twice the risk of the onset of postoperative symptoms, and 1.85 times the risk of unscheduled use of hospital services. Screening for patient activation in the preoperative setting could not only identify patients not suitable for early discharge, but more importantly, help physicians and nurses develop tailored interventions.

Electrocardiography in Children Hospitalized for COVID-19 and Not Suffering from Multisystem Inflammatory Syndrome in Children (MIS-C): An Observational Study.

The risk of cardiac involvement with electrophysiological abnormalities during COVID-19 infection has been reported in adults but remains poorly studied in children. Our aim was to determine the frequency of cardiac involvement and the necessity of routine cardiac evaluation in children hospitalized for COVID-19. This observational study included 127 children, with a median (IQR) age of 2 (0.83-6.0) years, who were hospitalized for COVID-19 between 1 January 2021 and 31 August 2022, 62 (48.8%) of whom were males. Each patient underwent an ECG on admission and discharge as well as a laboratory assessment. A comparison between patients with COVID-19 and healthy controls showed significantly higher HR (p < 0.0001) and lower PR values (p = 0.02) in the first group. No arrhythmias or other electrocardiographic abnormalities were detected during hospitalization. The median levels of troponin, NT-proBNP, ferritin, and D-dimer were significantly higher in children aged <2 years, but they fell within the normal range for their age. Our results indicate that a detectable cardiac involvement is very rare in children hospitalized for COVID-19 and not suffering from Multisystem Inflammatory Syndrome in Children (MIS-C) and suggest that routine electrocardiographic assessment is not mandatory in these patients in the absence of cardiac symptoms/signs.

Pulmonary Involvement in Recurrent Respiratory Papillomatosis: A Systematic Review.

Recurrent respiratory papillomatosis (RRP) is a non-malignant disease, characterized by the production of wart-like growths in the respiratory tract, affecting both young people and adults (juvenile-onset recurrent respiratory papillomatosis, JORRP, and adult-onset recurrent respiratory papillomatosis, AORRP, respectively). Infection caused by human papillomavirus (HPV) is known as the main factor involved in RRP development. Complications of RRP may rarely occur, including lung involvement and malignant transformation. The present systematic review aimed to evaluate the prevalence of severe complications, such as lung involvement and lung tumor in JORRP and AORRP patients, and assess the role of HPV genotypes in the progression of disease severity following the guideline for reporting systematic reviews and meta-analysis (PRISMA Statement). A total of 378 studies were found on PubMed and Scopus using the following MESH terms: "recurrent respiratory papillomatosis and lung tumor" and "pulmonary tumor and recurrent respiratory papillomatosis". Basing on inclusion and exclusion criteria, a total of 11 studies were included in the systematic review. We found a pooled prevalence of 8% (95% CI: 4-14%; I2: 87.5%) for lung involvement in RRP patients. In addition, we found a pooled risk difference of 5% in lung involvement between JORRP and AORRP (95% CI: -7-18%; I2: 85.6%, p-value: 0.41). Among patients with lung involvement, we observed a pooled prevalence of lung tumor of 4% (95% CI:1-7%; I2: 67.1%) and a pooled prevalence mortality for this group of 4% (95% CI:2-6%; I2: 0%). Overall, the positivity rate for HPV-6 and -11 in patients with RRP was 91%. Considering only cases with pulmonary involvement, the pooled prevalence for HPV-11 was 21% (95% CI: 5-45%; I2: 77.2%). Our results evidenced a low/middle risk of pulmonary involvement and lung tumor in JORRP and AORRP patients, with an increased risk for HPV-11-positive patients. Further studies should be performed to improve knowledge and adopt preventive measures to contrast the progression to severe diseases in RRP patients.

Vitamin D Status in an Italian Pediatric Cohort: Is There a Role for Tobacco Smoking Exposure?

Introduction: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy. Methods: A total of 182 children (males: 51.7%; median age: 9 years) were enrolled over a 12-month period. Serum 25(OH)D was measured by an immune-chemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure. Results: Mean (SD) serum 25(OH)D was 25.2 (8.3) ng/mL for the whole group. The majority (n=123, 67.6%) of children had vitamin D sufficient values >20 ng/mL, while about 1/3 had vitamin D insufficient/deficient values (≤20 ng/mL (n=59, 32.4%). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001). Conclusion: Our results further prove that hypovitaminosis D is common in the Italian children and documented that passive smoke exposure is a significant risk factor for hypovitaminosis D.

Epidemiology of seropositive myasthenia gravis in Sardinia: A population-based study in the district of Sassari.

INTRODUCTION/AIMS: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288). METHODS: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated. RESULTS: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%). DISCUSSION: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology.

Diagnostic delay in bronchiectasis: an Italian perspective.

It takes ∼3.5 years to reach a diagnosis of bronchiectasis from onset of symptoms: the long patient's journey in Italy https://bit.ly/46XMWAz.

Epidemiology of aquaporin-4-IgG-positive NMOSD in Sardinia.

PURPOSE: The Italian Island of Sardinia (population, 1,578,146) is recognized for the high risk of multiple sclerosis (MS) but the epidemiological burden of other less common demyelinating diseases of the central nervous system (CNS), such as aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+NMOSD), is unknown. In this study, we determined the incidence and prevalence of AQP4-IgG+NMOSD in Sardinia over a ten-year study period (2013-2022). METHODS: Patients with a diagnosis of AQP4-IgG+NMOSD (per 2015 IPND diagnostic criteria) were retrospectively identified using two sources: (1) Archives of the reference and only laboratory for AQP4-IgG testing in Sardinia; and (2) medical records of the four MS units in the island. Incidence (January 2013-December 2022) and prevalence (December 31, 2022) were calculated. RESULTS: A total of 45 cases were included: incident, 31; prevalent, 41. The median age (range) at disease presentation was 51 (6-78) years; female/male ratio was 9:1. The crude (95 % CI) incidence and prevalence were 1.9 (1.3-2.7) per million and 2.6 (1.9-3.5) per 100,000, respectively. Prevalence increased from 2013 (1.1 per 100,000) to 2022 (2.6 per 100,000); p = 0.002. After age-standardization to the world, incidence and prevalence (95 % CI) decreased to 1.3 (0.7-2) per million and 1.8 (1.3-2.3) per 100,000, respectively. Coexisting immune-mediated disorders, mostly autoimmune thyroiditis, were reported in 50 % of patients. CONCLUSIONS: The epidemiology of AQP4-IgG+NMOSD in Sardinia is overall in line with other Caucasian populations. The high MS risk in the island seems disease-specific and not associated with an increased risk of other CNS demyelinating disorders, confirming different pathophysiology.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

New score to predict COVID-19 progression in vaccine and early treatment era: the COVID-19 Sardinian Progression Score (CSPS).

BACKGROUND: Several scores aimed at predicting COVID-19 progression have been proposed. As the variables vaccination and early SARS-CoV-2 treatment were systematically excluded from the prognostic scores, the present study's objective was to develop a new model adapted to the current epidemiological scenario. METHODS: We included all patients evaluated by the Infectious Disease Unit in Sassari, with SARS-CoV-2 infection and without signs of respiratory failure at the first evaluation (P/F > 300). Disease progression was defined by the prescription of supplemental oxygen. In addition, variables related to demographics, vaccines, comorbidities, symptoms, CT scans, blood tests, and therapies were collected. Multivariate logistic regression modelling was performed to determine factors associated with progression; any variable with significant univariate test or clinical relevance was selected as a candidate for multivariate analysis. Hosmer-Lemeshow (HL) goodness of fit statistic was calculated. Odds ratio values were used to derive an integer score for developing an easy-to-use progression risk score. The discrimination performance of the risk index was determined using the AUC, and the best cut-off point, according to the Youden index, sensitivity, specificity, predictive value, and likelihood ratio, was chosen. RESULTS: 1145 patients [median (IQR) age 74 (62-83) years; 53.5% males] were enrolled; 336 (29.3%) had disease progression. Patients with a clinical progression were older and showed more comorbidities; furthermore, they were less vaccinated and exposed to preventive therapy. In the multivariate logistic regression analysis, age ≥ 60 years, COPD, dementia, haematological tumours, heart failure, exposure to no or one vaccine dose, fever, dyspnoea, GGO, consolidation, ferritin, De Ritis ≥ 1.2, LDH, and no exposure to early anti-SARS-CoV-2 treatment were associated with disease progression. The final risk score ranged from 0 to 45. The ROC curve analysis showed an AUC of 0.92 (95% CI 0.90-0.93) with a 93.7% specificity and 72.9% sensitivity. Low risk was defined when the cut-off value was less than 23. Three risk levels were identified: low (0-23 points), medium (24-35), and high (≥ 36). CONCLUSIONS: The proportion of patients with progression increases with high scores: the assessment of the risk could be helpful for clinicians to plan appropriate therapeutic strategies.

Impact of COVID-19 on patients with beta-thalassemia major: an observational study.

INTRODUCTION:  The prevalence of COVID-19 is slightly lower, and its mortality is higher in beta-thalassemia patients than in the general population. We evaluated the impact of COVID-19 in terms of incidence, clinical course, management, and specific antibody response to vaccination in a cohort of patients with beta-thalassemia major. METHODS:  We retrospectively enrolled all transfusion-dependent beta-thalassemia major patients attending the Thalassemia Day Care Center of the University Hospital of Sassari, Italy, from March 1, 2020, to May 31, 2021. For each patient, demographic, clinical, laboratory, instrumental, and therapy data were collected. Patients aged ≥16 years received two doses of mRNA COVID-19 vaccine. Anti-SARS-CoV-2 serum antibodies were tested before and after the first vaccine dose. RESULTS:  A total of 68 patients (median age: 36.5 years; IQR: 13-42 years) were included. Nasopharyngeal swab (NPS) for SARS-CoV-2 detection by RT-PCR was positive in 5 (7.35%) of 68 patients (4 symptomatic). No COVID-19-related complications, hospitalizations, or deaths were observed. The transfusion regimen and iron chelation therapy were not significantly changed. Prior to COVID-19 vaccination, anti-SARS-CoV-2 antibodies were tested in 61 patients, 51 negative and 10 positive; five of the latter were also positive for SARS-CoV-2 on NPS. The 46 vaccinated subjects had an antibody response, with higher levels in subjects previously infected with SARS-CoV-2. CONCLUSION:   Our findings suggest that patients with beta-thalassemia major are not at a higher risk of contracting SARS-CoV-2 infection and developing a severe form of COVID-19 despite being considered more vulnerable than the general population.

Tailored treatment for tuberculosis in transgender individuals: a call for a patient-centered approach from a large Italian cohort.

Tuberculosis (TB) diagnosis and management in special populations remain challenging. Data about TB and transgender individuals is scarce, and strategies aimed at reducing the TB burden in this at-risk group are needed. We conducted an observational monocentric study from a national reference center for TB, including transgender individuals with active TB in a low-TB burden country (Italy), over 34 years (1990-2023). Sixty-six transgender males and two transgender females (median age 30 years, interquartile range 26-38 years, 65 migrants) were included. Most patients (38/66, 57.6%) lived in poor social conditions. 65.2% (43/66) of patients were people living with HIV. Multidrug- and rifampicin-resistant tuberculosis and isoniazid-resistant TB were diagnosed in five (7.6%) and three (4.5%) patients, respectively. The overall treatment success rate was 72.7% (48/66 patients), with differences observed according to social conditions. Our study highlights the need for a tailored approach to increase treatment success in this at-risk population.

Comparison among populations with severe and intermediate alpha1-antitrypsin deficiency and chronic obstructive pulmonary disease.

BACKGROUND: Severe alpha1-antitrypsin (AAT) deficiency (AATD) is associated with a high risk of airflow obstruction and emphysema. The risk of lung disease in those with intermediate AAT deficiency is unclear. Our aims were to compare pulmonary function, time of onset of symptoms, and indicators of quality of life among patients with severe AATD (PI*ZZ), patients with intermediate AATD (PI*MZ) from the Italian Registry of AATD with a chronic obstructive pulmonary disease (COPD) cohort of patients without AATD (PI*MM). METHODS: We considered a total of 613 patients: 330 with the PI*ZZ genotype, 183 with the PI*MZ genotype and 100 with the PI*MM genotype. Radiological exams, pulmonary function test, and measurement of quality of life have been performed on all cohorts of patients. RESULTS: The three populations differ significantly in terms of age at COPD/AATD diagnosis (P=0.00001), respiratory function (FEV1, FVC, DLCO P<0.001), quality of life (P=0.0001) and smoking history (P<0.0001). PI*ZZ genotype had 24.9 times a higher likelihood of developing airflow obstruction. The MZ genotype is not associated with a significant early risk of airflow obstruction. CONCLUSIONS: The comparison of populations with PI*ZZ, MZ and MM genotypes allows to delineate the role of alpha1-antitrypsin deficiency on respiratory function and on the impact on quality of life, in relation to other risk factors. These results highlight the crucial role of primary and secondary prevention on smoking habits in PI*MZ subjects and the importance of an early diagnosis.

Synergistic properties of linezolid against Enterococcus spp. isolates: a systematic review from in vitro studies.

PURPOSE: Vancomycin-resistant enterococci (VRE) are a leading cause of hospital-acquired infections with limited therapeutic options. Combination of at least two antimicrobials is a possible strategy to obtain rapid and sustained bactericidal effects and overcome the emergence of resistance. We revised the literature on linezolid synergistic properties from in vitro studies to assess its activity in combination with molecules belonging to other antibiotic classes against Enterococcus spp. METHODS: We performed a systematic review of the literature from three peer-reviewed databases including papers evaluating linezolid synergistic properties in vitro against Enterococcus spp. isolates. RESULTS: We included 206 Enterococcus spp. isolates (92 E. faecalis, 90 E. faecium, 2 E. gallinarum, 3 E. casseliflavus, 19 Enterococcus spp.) from 24 studies. When an isolate was tested with different combinations, each combination was considered independently for further analysis. The most frequent interaction was indifferent effect (247/343, 72% of total interactions). The highest synergism rates were observed when linezolid was tested in combination with rifampin (10/49, 20.4% of interactions) and fosfomycin (16/84, 19.0%, of interactions). Antagonistic effect accounted for 7/343 (2.0%) of total interactions. CONCLUSION: Our study reported overall limited synergistic in vitro properties of linezolid with other antibiotics when tested against Enterococcus spp. The clinical choice of linezolid in combination with other antibiotics should be guided by reasoned empiric therapy in the suspicion of a polymicrobial infection or targeted therapy on microbiological results, rather than on an intended synergistic effect of the linezolid-based combination.

Pulmonary rehabilitation and risk of fall in elderly with chronic obstructive pulmonary disease.

BACKGROUND: Few data are available on the effects of pulmonary rehabilitation (PR) on risk of fall in over 80 individuals with chronic obstructive pulmonary disease (COPD). We investigated the effectiveness of PR on the risk of fall in older as compared to younger than 80 individuals. METHODS: Parallel-group retrospective exploratory study of individuals undergone in-hospital PR. The risk of fall was defined as a gait speed ≤0.8 m/s (primary outcome). Outcome measures (exercise capacity, physical performance, symptoms, and health status) were also assessed. RESULTS: As compared to younger, individuals over 80 suffered from more severe symptoms, a reduction in physical performance and in exercise capacity and greater risk of fall (P=0.0001). The proportion of participants at risk of fall increased with age, and after PR decreased significantly without any significant difference between age groups. However, 53.4% of older individuals were still at risk of fall, as compared to 17.5% of those under 80 (P=0.0001). After PR, both populations had improved outcomes measures, without any significant between group differences. CONCLUSIONS: In individuals with COPD pulmonary rehabilitation reduced the risk of fall, while improving outcome measures independent of age, however, more than 50% of those over 80 were still at risk of fall. The pulmonary rehabilitation programs for individuals over 80 should include strategies effective in reducing the risk of fall.

Two-stage targeted maximum likelihood estimation for mixed aggregate and individual participant data analysis with an application to multidrug resistant tuberculosis.

In this study, we develop a new method for the meta-analysis of mixed aggregate data (AD) and individual participant data (IPD). The method is an adaptation of inverse probability weighted targeted maximum likelihood estimation (IPW-TMLE), which was initially proposed for two-stage sampled data. Our methods are motivated by a systematic review investigating treatment effectiveness for multidrug resistant tuberculosis (MDR-TB) where the available data include IPD from some studies but only AD from others. One complication in this application is that participants with MDR-TB are typically treated with multiple antimicrobial agents where many such medications were not observed in all studies considered in the meta-analysis. We focus here on the estimation of the expected potential outcome while intervening on a specific medication but not intervening on any others. Our method involves the implementation of a TMLE that transports the estimation from studies where the treatment is observed to the full target population. A second weighting component adjusts for the studies with missing (inaccessible) IPD. We demonstrate the properties of the proposed method and contrast it with alternative approaches in a simulation study. We finally apply this method to estimate treatment effectiveness in the MDR-TB case study.

Impact of bronchoalveolar lavage on the management of immunocompromised hosts.

BACKGROUND: Respiratory infections are an important cause of morbidity and mortality in immunocompromised individuals. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is an important tool to detect infectious agents in immunocompromised patients with low respiratory tract infections (LRTI). RESEARCH QUESTION: BAL changes the management of immunocompromised patients with suspected LRTI. STUDY DESIGN AND METHODS: Immunocompromised patients with a suspicion of LRTI underwent diagnostic BAL. The primary composite outcome consisted of pre-defined modifications in the management of the immunocompromised patients following BAL. We quantified the impact of bronchoscopy up to 30 days after the procedure. RESULTS: A total of 2666 visits from 1301 patients were included in the study and immunosuppression was classified as haematological (n = 1040; 544 patients), solid organ transplantation (n = 666; 107 patients) and other causes (n = 960; 650 patients). BAL led to a change in management in 52.36% (n = 1396) of all cases. This percentage, as well as the 30-day mortality differed significantly amongst the three groups. Age, C-reactive protein and aetiology of infection determined significantly the risk of 30-day mortality in all patients. In 1.89% (n = 50) of all cases, a combination of 2 respiratory viral agents was identified and 24.23% (n = 646) were diagnosed with a single respiratory viral agent. INTERPRETATION: BAL leads to changes in management in the majority of immunosuppressed patients. There is a high prevalence of multimicrobial infections and respiratory viral infections in immunocompromised patients with respiratory symptoms. Individual virus infection is associated with diverse risk of a negative outcome.