Long-term effects of pulmonary endarterectomy on pulmonary hemodynamics, cardiac function, and exercise capacity in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Long-term changes in exercise capacity and cardiopulmonary hemodynamics after pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) have been poorly described. METHODS: We analyzed the data from 2 prospective surgical CTEPH cohorts in Hammersmith Hospital, London, and Amsterdam UMC. A structured multimodal follow-up was adopted, consisting of right heart catheterization, cardiac magnetic resonance imaging, and cardiopulmonary exercise testing before and after PEA. Preoperative predictors of residual pulmonary hypertension (PH; mean pulmonary artery pressure >20 mm Hg and pulmonary vascular resistance ≥2 WU) and long-term exercise intolerance (VO2max <80%) at 18 months were analyzed. RESULTS: A total of 118 patients (61 from London and 57 from Amsterdam) were included in the analysis. Both cohorts displayed a significant improvement of pulmonary hemodynamics, right ventricular (RV) function, and exercise capacity 6 months after PEA. Between 6 and 18 months after PEA, there were no further improvements in hemodynamics and RV function, but the proportion of patients with impaired exercise capacity was high and slightly increased over time (52%-59% from 6 to 18 months). Long-term exercise intolerance was common and associated with preoperative diffusion capacity for carbon monoxide (DLCO), preoperative mixed venous oxygen saturation, and postoperative PH and right ventricular ejection fraction (RVEF). Clinically significant RV deterioration (RVEF decline >3%; 5 [9%] of 57 patients) and recurrent PH (5 [14%] of 36 patients) rarely occurred beyond 6 months after PEA. Age and preoperative DLCO were predictors of residual PH post-PEA. CONCLUSIONS: Restoration in exercise tolerance, cardiopulmonary hemodynamics, and RV function occurs within 6 months. No substantial changes occurred between 6 and 18 months after PEA in the Amsterdam cohort. Nevertheless, long-term exercise intolerance is common and associated with postoperative RV function.

Bronchoscopy in the post-acute phase of COVID-19: an observational study.

BACKGROUND: Bronchoscopy is a useful technique adopted in the management of patients with COVID-19. 10-40% of COVID-19 survivors experience persistent symptoms. A comprehensive description of the utility and safety of bronchoscopy in the management of patients with COVID-19 sequelae is lacking. The aim of the study was to evaluate the role of bronchoscopy in patients with suspected post-acute sequelae of COVID-19. METHODS: An observational, retrospective study was carried out in Italy. Patients requiring bronchoscopy for suspected COVID-19 sequelae were enrolled. RESULTS: 45 (21, 46.7%, female) patients were recruited. Bronchoscopy was more frequently indicated for patients with a previous critical disease. The most frequent indications were tracheal complications, mostly performed in patients who were hospitalized during the acute phase than treated at home (14, 48.3% VS. 1, 6.3%; p-value: 0.007) and persistent parenchymal infiltrates, more frequent in those treated at home (9, 56.3% VS. 5, 17.2%; p-value: 0.008). 3 (6.6%) patients after the first bronchoscopy required higher oxygen flow. Four patients were diagnosed with lung cancer. CONCLUSION: Bronchoscopy is a useful and safe technique in patients with suspected post-acute sequelae of COVID-19. The severity of acute disease plays a role in the rate and indications of bronchoscopy. Endoscopic procedures were mostly performed for tracheal complications in critical, hospitalized patients and for persistent lung parenchymal infiltrates in mild-moderate infections treated at home.

Does the severity of asthma affect exercise capacity and daily physical activity?

OBJECTIVE: Exercise capacity, daily physical activity, and psychological profile are crucial aspects in the management of asthmatic patients. Whether these features are expressed in a different way in mild-moderate (MMA) and severe asthma (SA) is unknown. METHODS: In this observational cross-sectional study, patients matching the American Thoracic Society/European Respiratory Society (ATS/ERS) definition for SA underwent incremental cardiopulmonary exercise testing (CPET), full lung function testing, and an evaluation of daily step count and physical activity. Questionnaires on quality of life, general fatigue, and presence of anxiety and depression traits (Hospital Anxiety and Depression Scale - HADS) were administered. Patients were compared with a cohort of age- and gender-matched MMA patients. RESULTS: We enrolled 16 SA, 17 MMA patients, and 16 healthy subjects. Compared to MMA, SA subjects showed a median (interquartile range) reduced peak oxygen consumption during CPET (20.4 (17.2-23.3) vs. 25.6 (18.5-30.3) ml/min/kg; p = 0.019), a reduced resting lung function (FEV1% of predicted 77 (67-84) vs. 96 (84-100); p < 0.001) and a pronounced anxiety trait at HADS (9.5 (3-11.7) vs. 4.0 (2.0-7.5); p = 0.023). In addition, SA patients showed a significantly higher reduction in inspiratory capacity from rest to peak (310 (160-520) vs. 110 (-65-325) ml; p = 0.031). We found no significant differences in mean daily step count or quality of life. CONCLUSIONS: Compared to MMA, SA patients present a reduced exercise capacity and a more pronounced anxiety trait, but not worse daily physical activity or quality of life. These aspects should be considered in the clinical management and research development of SA.

Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension.

BACKGROUND: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. METHODS: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. RESULTS: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO2 peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO2 peak ≥14 ml/kg/min and SVI >30 ml/m2; Group 2, score between 2 and 5 (112 patients) with VO2 peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m2; Group 3, score >5 (46 patients) with VO2 peak <10 ml/kg/min and SVI <30 ml/m2. The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. CONCLUSIONS: Combinations of VO2 peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.

The role of phenotype on ventilation and exercise capacity in patients affected by COPD: a retrospective study.

Background: The idea of phenotype in chronic obstructive pulmonary disease (COPD) has evolved in the last decades, and the importance of peculiar treatment strategies has now been acknowledged. Although dyspnea and exercise limitation are hallmarks of COPD, this aspect has never been fully explored in literature in terms of disease phenotype. The aim of the present study was to explore the relevance of clinical COPD phenotypes on exercise ventilation and maximal capacity. Methods: In this observational cohort retrospective study we analyzed the data of 50 COPD patients who underwent cardiopulmonary exercise test, categorized as emphysematous (n=29), and non-emphysematous (n=21) according to a previously validated model. Results: We found a significant difference in terms of VE/VCO2 slope (median values 32.4 vs 28.0, p=0.015) and VE/VCO2 ratio at nadir (median values 37 vs. 33, p=0.004), which resulted higher in emphysematous patients, who also presented lower PETCO2 values (median values 32.6 vs 35.6, p=0.008). In a subgroup of 31 tests which met the maximality criteria, emphysematous patients presented a significantly lower work rate at peak (median value 51 vs 72% predicted, p=0.016), and showed a lower peak oxygen consumption, although at the limit of significance (median values of 63 vs 85 % predicted, p=0.051). Conclusions: This study extends our knowledge about the characterization of the COPD phenotypical expression of disease, showing that patients affected by emphysema are more prone to ventilatory inefficiency during exercise, and that this is likely to be an important cause of their overall reduced exercise capacity.

Clinical Use and Barriers of Thoracic Ultrasound: A Survey of Italian Pulmonologists.

INTRODUCTION: Thoracic ultrasound is accurate in the diagnosis of a wide range of respiratory diseases. Yet the extent of its use is unknown. Through a national survey, we aimed to explore the clinical use of thoracic ultrasound and the barriers to the diffusion of the technique in Italy. METHODS: Accademia di Ecografia Toracica (AdET) developed a self-administered survey which was sent by email to Italian pulmonologists via national scientific societies and networks. RESULTS: Of the 2010 physicians invited, 514 completed the survey (26% response rate). According to 99% of responders, thoracic ultrasound had a relevant clinical role. Seventy-nine percent of the responders used thoracic ultrasound at least once a month. The main settings were: 53% pulmonology ward, 15% outpatient clinic, 15% interventional pulmonology room, 10% internal medicine ward, 4% respiratory intensive care units, and 9% other. Thoracic ultrasound was primarily used: (1) with both diagnostic and interventional aims (72%), (2) as diagnostic imaging (17%), and (3) as guidance for interventional procedures (11%). The main clinical applications were: (1) diagnosis and management of pleural effusion, (2) pneumothorax, (3) pneumonia, (4) cardiac failure, and (5) acute dyspnea. Twenty-one percent of the responders do not use thoracic ultrasound. The main reported bar-riers were: (1) availability of an ultrasound system (52%), (2) lack of protected time and training (22%), and (3) use of the technique by other specialists (15%). CONCLUSION: Thoracic ultrasound is widely used by Italian pulmonologists and considered a clinically relevant tool. The availability of dedicated ultrasound systems seems to be a major limit of the use of the technique.

A path model analysis on predictors of dropout (at 6 and 12 months) during the weight loss interventions in endocrinology outpatient division.

INTRODUCTION: This study aimed to identify the dropout rate at 6 and 12 months from the first outpatient visit, and to analyze dropout risk factors among the following areas: biochemical examinations, anthropometric measures, psychological tests, personal data, and life attitude such as smoking, physical activity, and pathologies. METHODS: This is a retrospective longitudinal observational study. Patients undergo an outpatient endocrinology visit, which includes collecting biographical data, anthropometric measurements, physical and pathological history, psychological tests, and biochemical examinations. RESULTS: The sample consists of 913 subjects (682 women and 231 men), with an average age of 50.88 years (±15.80) for the total sample, with a BMI of 33.11 ± 5.65 kg/m2. 51.9% of the patients abandoned therapy at 6 months after their first visit, and analyzing the dropout rate at 12 months, it appears that 69.5% of subjects abandon therapy. The main predictor of dropout risk factors at 6 and 12 months is the weight loss during the first 3 months (p < 0.05). As regards the hematological predictors, white blood cell and iron level stated dropout at 12 months. Patients who introduced physical activity had a reduction of - 17% (at 6 months) and -13% (at 12 months) of dropout risk (p < 0.05). As regards the "worker" status, patients classified as"retired" had a decrease risk of dropout vs. other categories of worker (i = 0.58; p < 0.05). Dropout risk at 12 months decrease in patients with a previous history of cancer, Endocrine and psychic and behavioral disorders (p < 0.001). CONCLUSIONS: The main factor that predisposes patients to continue therapy or to abandon it is the success (or failure) of the diet in the initial period, based on weight lost (or not lost) in the early months of the initiation of therapy. Furthermore, considerable differences were found in different categories of "workers", and with previous "pathologies". The level of physical activity and previous diseases also seem to be predictors of dropout.

Association of the bitter taste receptor gene TAS2R38 (polymorphism RS713598) with sensory responsiveness, food preferences, biochemical parameters and body-composition markers. A cross-sectional study in Italy.

This study examined the relationship between TAS2R38 gene polymorphism (RS713598), G/G, C/G or C/C genotype, and sensory responsiveness, food preferences, biochemical parameters and body composition in a cross-sectional study in 118 adults (24 men and 94 women). The frequencies of C/C, G/G and C/G were respectively 20.3%, 29.7% and 50.0%. As regards taste responsiveness, subjects with G-allele had a higher perception threshold than the C/C genotype for 6-n-propyl-2-thiouracil (PROP) (p < .05), and caffeine (p < .05). The G-alleles had higher preferences for beer (OR: 6.25; p < .05), but lower for butter (OR: 0.64; p < .05) and cured meat (OR: 0.55; p < .05). Biochemical parameters and body composition markers did not differ between genotypes. Subjects with RS713598 polymorphism had a higher bitter taste perception threshold and higher or lower preferences for selected nutrient/energy dense foods, such as beer, butter and cured meat.

Performance of Edmonton Frail Scale on frailty assessment: its association with multi-dimensional geriatric conditions assessed with specific screening tools.

BACKGROUND: The aim of this study was to evaluate the performance of Edmonton Frail Scale (EFS) on frailty assessment in association with multi-dimensional conditions assessed with specific screening tools and to explore the prevalence of frailty by gender. METHODS: We enrolled 366 hospitalised patients (women\men: 251\115), mean age 81.5 years. The EFS was given to the patients to evaluate their frailty. Then we collected data concerning cognitive status through Mini-Mental State Examination (MMSE), health status (evaluated with the number of diseases), functional independence (Barthel Index and Activities Daily Living; BI, ADL, IADL), use of drugs (counting of drugs taken every day), Mini Nutritional Assessment (MNA), Geriatric Depression Scale (GDS), Skeletal Muscle Index of sarcopenia (SMI), osteoporosis and functionality (Handgrip strength). RESULTS: According with the EFS, the 19.7% of subjects were classified as non frail, 66.4% as apparently vulnerable and 13.9% with severe frailty. The EFS scores were associated with cognition (MMSE: ß = 0.980; p < 0.01), functional independence (ADL: ß = -0.512; p < 0.00); (IADL: ß = -0.338; p < 0.01); use of medications (ß = 0.110; p < 0.01); nutrition (MNA: ß = -0.413; p < 0.01); mood (GDS: ß = -0.324; p < 0.01); functional performance (Handgrip: ß = -0.114, p < 0.01) (BI: ß = -0.037; p < 0.01), but not with number of comorbidities (ß = 0.108; p = 0.052). In osteoporotic patients versus not-osteoporotic patients the mean EFS score did not differ between groups (women: p = 0.365; men: p = 0.088), whereas in Sarcopenic versus not-Sarcopenic patients, there was a significant differences in women: p < 0.05. CONCLUSIONS: This study suggests that measuring frailty with EFS is helpful and performance tool for stratifying the state of fragility in a group of institutionalized elderly. As matter of facts the EFS has been shown to be associated with several geriatric conditions such independence, drugs assumption, mood, mental, functional and nutritional status.

Telomerase in differentiated thyroid cancer: promoter mutations, expression and localization.

Telomerase-reverse-transcriptase (TERT) promoter mutations have been recently described in tumors. In the present large series, TERT mutations were found in 12% of papillary thyroid cancers (PTCs) and in 14% of follicular thyroid cancers (FTCs), and were found to significantly correlate with older age at diagnosis and poorer outcome. Interestingly, the prognostic value of TERT mutations resulted to be significantly stronger than that of BRAF(V600E). Moreover, the outcome was not different among tumors with isolated TERT mutation and those with coexistent mutations (TERT/BRAF in PTCs or TERT/RAS in FTCs). TERT rs2853669 polymorphism was found in 44.4% of tumors. At WB, TERT was significantly more expressed in tumors than in normal samples, being the highest levels of expression recorded in TERT mutated cases. At IHC, in tumors and in metastatic lymph-nodes TERT staining was significantly higher in the cytoplasm than in the nucleus, whereas in normal tissue the degree of staining did not differ in the two cellular compartments. In conclusion, TERT mutations were shown to strongly correlate with a poorer outcome in differentiated thyroid tumors, and neither BRAF nor RAS mutation were found to confer an additional effect in the disease persistence. TERT protein was found to be more expressed in neoplastic than in normal tissues, and to display a different cellular localization, suggesting that it could contribute to thyroid cancer progression by mechanisms taking place in the cytoplasm.