Introduction: Emphysema is frequently observed in patients with fibrosing interstitial lung diseases (f-ILDs), leading to the clinical entity known as combined pulmonary fibrosis and emphysema (CPFE). This study aimed to evaluate the utility of airwave oscillometry (AOS) in detecting small-airway dysfunction (SAD) in patients with CPFE. Due to the coexistence of both restrictive and obstructive airway disease, spirometry is comparatively less sensitive in detecting airflow limitations in this population. Methods: A cohort of 52 patients with CPFE was recruited from Monaldi Hospital, Naples, between January and September 2023. Pulmonary function tests-including spirometry, body plethysmography, and single-breath diffusing capacity for carbon monoxide (DLCO)-were performed at baseline and following bronchodilator administration. Patients with normal FEV1/FVC ratios underwent airwave oscillometry (AOS) to assess respiratory system resistance (Rrs) and reactance (Xrs), with SAD defined as an R5-R19 value greater than 0.07 kPa·s·L-1. Results: AOS-defined SAD was present in 40.4% (21/52) of the cohort. The R5-R19 value in the SAD group was 0.13 ± 0.05 kPa·s·L-1, which can be compared to 0.04 ± 0.02 kPa·s·L-1 in patients without SAD. Patients with SAD were more likely to be undergoing maintenance bronchodilator therapy (16/21; 76.2%) than those without SAD (8/31; 25.8%) (p = 0.015). Fourteen CPFE patients met the criteria for bronchial responsiveness. CPFE patients who responded to bronchodilators had lower R5-R19 values than non-responders (0.04 ± 0.02 vs. 0.09 ± 0.06 kPa·s·L-1; p = 0.04). Discussion: Although AOS parameters did not significantly change following bronchodilator administration, this study underscores the value of AOS in detecting peripheral airway dysfunction, which may be under-recognized by conventional spirometry. Conclusions: AOS shows promise as a diagnostic adjunct for identifying SAD in CPFE patients and may complement standard pulmonary function testing in clinical practice. Further multicenter studies with larger cohorts are warranted to validate these findings and investigate the longitudinal impact of SAD on disease progression and treatment outcomes in CPFE.
In the Article titled "Epidemiology and clinical outcomes of non-COVID viral respiratory infections in children from a low-middle-income country" (doi: 10.4081/monaldi.2025.3227) published on October 9, 2025, there is a change in the order of authorship. The change in authorship order was requested for academic promotion purposes, as authorship order must align with individual contributions. Therefore, revising the order to list Syda Asma Sherazi as first author and Ali Faisal Saleem as the last one ensures appropriate recognition and transparency.
Activating PIK3CA mutations occur in approximately 40% of hormone receptor-positive (HR+)/HER2-negative breast cancers and represent a major driver of endocrine resistance. The PI3Kα-selective inhibitor alpelisib, in combination with fulvestrant, significantly improves progression-free survival in patients with PIK3CA-mutant disease, as demonstrated in the SOLAR-1 trial. However, this therapeutic strategy is frequently complicated by treatment-induced hyperglycemia, a metabolic disturbance that promotes oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby increasing cardiovascular vulnerability. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as cardiometabolic modulators with benefits extending beyond glucose lowering. In this study, we used a human cardiomyocyte in vitro model designed to recapitulate the hyperglycemic metabolic milieu observed in breast cancer patients receiving PI3Kα-targeted therapy, to investigate whether the SGLT2 inhibitor dapagliflozin directly protects cardiomyocytes from alpelisib- and fulvestrant-induced injury. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured under hyperglycemic conditions (25 mM glucose) to mimic the metabolic environment associated with PI3Kα inhibitor-induced dysglycemia. Cells were exposed to alpelisib (100 nM) and fulvestrant (100 nM), alone or in combination, in the absence or presence of dapagliflozin (1 μM). Cardiomyocyte viability was assessed using the MTS assay, mitochondrial function by TMRM-based mitochondrial membrane potential (ΔΨm) measurements, and apoptosis by caspase-3 quantification. Cardiomyocyte injury was evaluated by release of cardiac troponin I and heart-type fatty acid binding protein (H-FABP). Lipid peroxidation markers (MDA and 4-HNE) were measured to assess oxidative membrane damage. Intracellular inflammasome-related signaling (NLRP3 and MyD88) and secreted inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2) were quantified by ELISA. Exposure to alpelisib, particularly in combination with fulvestrant, significantly reduced cardiomyocyte viability, induced mitochondrial depolarization, and increased caspase-3-mediated apoptotic signaling. These alterations were accompanied by elevated lipid peroxidation (MDA and 4-HNE) and increased release of cardiac injury biomarkers (troponin I and H-FABP). Alpelisib-based treatments also activated inflammasome-related signaling, as indicated by increased intracellular NLRP3 and MyD88 levels and enhanced secretion of pro-inflammatory mediators (IL-1β, IL-18, IL-6, TNF-α, and CCL2). Co-treatment with dapagliflozin significantly attenuated these alterations, preserving mitochondrial membrane potential, reducing apoptotic signaling, limiting oxidative membrane damage, and suppressing inflammatory cytokine release. This study provides evidence that alpelisib-based therapy under hyperglycemic conditions is associated with oxidative, mitochondrial, and inflammatory stress responses in human cardiomyocytes, recapitulating key features of cardiometabolic stress relevant to PI3Kα-targeted therapy. Importantly, dapagliflozin markedly attenuated these alterations, supporting a potential cardioprotective role that may extend beyond glycemic control. These findings provide a mechanistic rationale for further investigation of SGLT2 inhibition as a cardiometabolic protective strategy in patients receiving PI3Kα inhibitor-based cancer therapy.
For patients with pulmonary arterial hypertension (PAH), current guidelines recommend a 3- and 4-strata risk stratification model at baseline and follow-up, respectively. Risk stratification models in PAH are mainly derived from idiopathic PAH cohorts and are not automatically applicable to all patients with PAH associated with congenital heart disease (CHD), especially in those with Eisenmenger syndrome, given the differences in pathophysiology and clinical phenotype. Additional features such as shunt location, complexity of CHD, degree of cyanosis, iron deficiency, syndromic co-morbidity and biomarkers, other than brain natriuretic peptide may play an important role in the prognostication of these patients. This scientific statement aims to discuss in detail individual prognosticators and propose a comprehensive model of risk stratification for patients with PAH-CHD, mainly those with Eisenmenger syndrome.
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A significant number of hospitals within the Italian National Health System are involved in the field of foetal cardiology. To date, there has been no investigation into the activity of these centres. The foetal working group of the Italian Society of Paediatric Cardiology (SICP) prepared a survey to outline a current overview of the foetal cardiology activity in Italy. A 23-item web-based questionnaire, developed ad hoc, was administered to all members of the SICP by e-mail. The survey was conducted online from 1 March to July 31, 2024. Forty-five specialists in paediatric cardiology out of 548 SICP members (8.2%) completed the survey: 18/45(40%) from Northern, 10/45(22.2%) from Central and 17/45(37.7%) from Southern Italy. The respondents' answers indicate that counselling is conducted in all cases by foetal cardiologists. There is a frequent availability of geneticists (37/43 - 86%), paediatric specialists (32/42 - 76.1%), psychologists (33/43 - 76.7%), less frequent (25/42- 60%) is the opportunity to involve the cardiac surgeon during counselling. Eight of 44(18.1%) participants reported that foetal intervention procedures are performed at their centre, and 8/42(19%) can propose foetal magnetic resonance imaging. Despite the low response rate, the survey highlights that activity in foetal cardiology is unevenly distributed across the country. The need for national shared guidelines on the conduct of the foetal cardiology session and guidance on the necessary training for operators has been identified. Furthermore, the establishment of a defined network between hub-and-spoke facilities and care services on a national scale is a priority.
Hydropneumothorax is an uncommon but serious complication of pulmonary tuberculosis (PTB), often resulting from the rupture of a tuberculous cavity into the pleural space with bronchopleural fistula formation. Early diagnosis and optimal management are crucial to improving outcomes. A descriptive study was conducted over 18 months in 50 microbiologically confirmed PTB patients presenting with pneumothorax or hydropneumothorax at a tertiary care hospital in Punjab, India. Demographic, clinical, radiological, and microbiological data were recorded. Lung expansion was quantified using Light's Index at serial intervals up to 8 weeks. Statistical analysis was performed using Chi-square/Fisher exact tests; p<0.05 was considered significant. The mean age was 34.48±11.69 years, and 82% were male. All patients presented with breathlessness, 96% with chest pain, 68% with fever, and 62% with cough. New TB cases comprised 82%, recurrent 8%, and loss-to-follow-up 10%. The mean lung expansion time was 2.92±2.16 weeks. Significant associations were found between drainage status and lung expansion (p=0.01) and between type of TB and lung expansion (p=0.04). Complete radiological expansion was achieved in 76% of patients within 8 weeks. Surgical referral to the Cardiothoracic and Vascular Surgery Department was required in 24%. Hydropneumothorax in PTB predominantly affects young adult males and often requires prolonged drainage. Early intercostal tube drainage significantly improves lung expansion outcomes, particularly in new TB cases.
Sarcopenia and osteoporosis are important comorbidities in patients with chronic obstructive pulmonary disease (COPD). We compared the prevalence and impact of these comorbidities in tobacco-smoke-related COPD (S-COPD) and non-tobacco-smoke-related COPD (NS-COPD). The utility of rectus femoris ultrasonography as a screening tool for sarcopenia was also explored. This cross-sectional study was conducted in a tertiary care hospital in Southern India. The COPD Assessment Test (CAT), St. George's Respiratory Questionnaire, 6-minute walk test, dual energy X-ray absorptiometry and rectus femoris ultrasonography were performed in all included participants. One hundred participants (73% S-COPD and 27% NS-COPD, respectively) were included with a mean (standard deviation - SD) age of 65.8 (8.6) years and a mean (SD) predicted forced expiratory volume at one second of 41.1% (12.6). NS-COPD participants were younger (60.7 vs. 67.5 years; p<0.001), predominantly female (88.9% vs. 1.4%; p<0.001) and had a higher body mass index (BMI) (24.8 kg/m² vs. 21.8 kg/m², p=0.004) compared to S-COPD. Sarcopenia and osteoporosis were diagnosed in 36% and 12%, respectively. Older males with S-COPD and lower BMI were sarcopenic, and the latter was an independent predictor of lower 6-minute walk distance [adjusted b = -51.4 m; 95% confidence interval (CI) = -97.0, -5.84] and higher CAT scores (adjusted b = 2.53; 95% CI = 0.21, 4.86). Rectus femoris cross-sectional area at a cut-off value of 4.34 cm² had 91% sensitivity and 87% negative predictive value for sarcopenia. Sarcopenia was more prevalent among older male smokers and was an independent risk factor for high symptom burden and poor exercise capacity. Rectus femoris ultrasonography is a potential screening tool for sarcopenia.
Bacteremia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is associated with high morbidity and mortality. The primary objective was to identify clinical and therapeutic factors associated with 14- and 30-day mortality following infection onset. This was a prospective, observational, multicenter study conducted across 52 Italian centers. Over an 18-month period, adult hospitalized patients with CRAB bacteremia were enrolled. Among 398 patients with CRAB bacteremia, sources were mainly CVC-related or primary, with 14- and 30-day mortality rates of 22% and 27% respectively. Cox regression analysis identified male sex (p=0.006), and chronic kidney disease (p=0.016) as independent predictors of 14-day mortality, while colistin-containing regimen (p=0.014), and cefiderocol-containing-regimen (p<0.001) were associated with 14-day survival; male sex (p=0.027), septic shock (p=0.018), previous colonization by A. baumannii (p<0.001), and tigecycline-containing regimen (p=0.021) were independent predictors of 30-day mortality, while cefiderocol-containing-regimen (p<0.001) was associated with 30-day survival. Propensity score matching revealed that cefiderocol was significantly associated with 14-day survival and clinical success. The combination of cefiderocol plus Fosfomycin was also significantly associated with clinical success. Our findings highlight key clinical and therapeutic determinants of mortality and survival in patients with CRAB bacteraemia, providing valuable insights for improving the management of this challenging infection.
Chronic airway diseases, such as asthma and COPD, are major contributors to global morbidity and the healthcare burden. Due to their heterogeneity and sensitivity to environmental factors, including air pollution, tobacco smoke, and occupational exposures, they are critical models for examining how the environment shapes disease biology and treatment response. This expert narrative review integrates mechanistic, clinical, and epidemiological evidence on the impact of environmental exposures on the biology of airway disease and therapeutic outcomes. A structured literature search was performed, prioritizing mechanistic studies, large cohorts, randomized trials, and high-quality reviews relevant to asthma and COPD endotypes, phenotypes, and environment-adaptive therapies. The evidence indicates that environmental exposures modulate inflammatory pathways, oxidative stress, and drug responsiveness. These exposures often account for variability in clinical outcomes and apparent treatment resistance. Environmental exposures should be recognized as core biological modifiers that directly impact therapeutic efficacy, dosing requirements, and safety. Incorporating a systematic approach to environmental assessment into precision respiratory medicine allows for environment-adaptive therapies, optimizes pharmacological interventions, and reduces the risk of overtreatment. Future research and clinical protocols should integrate exposure metrics to personalize therapy, improve symptom control, and enhance long-term outcomes for patients with asthma and COPD.
Peripheral artery disease (PAD) is a pervasive atherosclerotic condition affecting well over 100 million adults worldwide and associated with major functional limitations, reduced quality of life, and elevated risks of myocardial infarction, stroke, limb events, and mortality. Exercise therapy-preferably supervised or delivered through structured, monitored home-based programs-is a first-line, guideline-endorsed therapy that improves walking performance and patient-reported outcomes and contributes to comprehensive secondary prevention. This review synthesizes mechanistic underpinnings (endothelial, angiogenic, metabolic, and autonomic) and appraises the comparative effectiveness, safety, and implementation models of supervised exercise therapy (SET), structured home-based and hybrid programs, and alternative modalities in PAD. Finally, we summarize policy aspects and persistent gaps to guide clinical practice and future research.
Pneumonia is a significant cause of morbidity and mortality, particularly among 5-year-olds, the elderly population, and those with comorbid conditions. As antibiotics are the most commonly used drugs, they need to be selected rationally to improve the therapeutic outcomes as well as to limit the emergence of antimicrobial resistance (AMR). This prospective observational study was carried out at Vivekananda Hospital, Hubballi, Karnataka, India, from October 2024 to March 2025. The data, such as demographics, laboratory values, patterns of prescription, and utilization trends from 200 study subjects, were collected, analyzed, and statistically tested using descriptive analysis. The World Health Organization core drug prescribing indicators revealed an average of 9775 drugs per prescription, of which antibiotics constitute 28.51%, with all prescriptions containing at least one antibiotic. Also, there is a high prevalence of polypharmacy, with the majority of prescriptions containing two or more antibiotics. The most commonly prescribed antibiotic was azithromycin, followed by ceftriaxone and piperacillin + tazobactam and the highest defined daily dose (DDD)/1000/days was observed in azithromycin (9.85), indicating potential overuse, whereas linezolid and cefixime had a prescriber daily dose value equal to DDD. The study emphasizes the need for improvement in generic prescribing, including the use of culture sensitivity tests for selection of appropriate antibiotics and implementation of an Antimicrobial Stewardship Program to optimize the antibiotic use and minimize the development of AMR.
Pleural mesothelioma (PM) is a rare and aggressive cancer arising from pleural mesothelial cells with a strong association to asbestos exposure. Among the diagnostic strategies available are noninvasive techniques including thoracic ultrasound (TUS), computed tomography (CT) scans, positron emission tomography (PET-CT), and invasive procedures such as thoracoscopy and pleural biopsy. Accurate identification of the histological subtype is critical for tailoring treatment strategies. The standard treatment for unresectable PM has traditionally been chemotherapy, particularly platinum and pemetrexed. However, recent advances in translational clinical research, including immune checkpoint inhibitors (ICIs), are changing the therapeutic landscape, offering new opportunities for personalized treatment. The recent FDA approval of nivolumab and ipilimumab combination therapy as a first-line treatment has significantly improved outcomes, especially for nonepithelioid subtypes. Ongoing studies are exploring additional immune-targeted therapies such as VISTA, LAG-3, and dendritic cell-based therapies. Early detection, refined biomarker identification, and a deeper understanding of the tumor microenvironment remain essential to improving PM prognosis and patient survival. This review provides a comprehensive exploration of the epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and molecular markers), staging, and current treatment strategies for PM.
The study aimed to evaluate the relationship of kinesiophobia with functional capacity, psychological distress, pulmonary function, and quality of life in individuals with obstructive airway disease and to determine the variables that independently predict kinesiophobia. A total of 111 clinically stable patients with obstructive airway disease were assessed using the Tampa Scale for Kinesiophobia (TSK), Numerical Rating Scale (NRS), Modified Medical Research Council Dyspnea Scale (mMRC), Fatigue Severity Scale (FSS), 6-Minute Walk Test (6MWT), International Physical Activity Questionnaire (IPAQ), arm curl test, 30-second sit-to-stand and flexibility tests, pulmonary function test, Depression Anxiety Stress Scale-21 (DASS-21), WHO Quality of Life-BREF (WHOQOL-BREF), and WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). Clinically significant kinesiophobia (TSK>37) was observed in 64.8% of participants. TSK scores showed significant positive correlations with NRS (r=0.431), FSS (r=0.554), DASS-21 (r=0.456), WHODAS 2.0 (r=0.434), mMRC (r=0.309), and flexibility (back scratch test (r=0.281); and significant negative correlations with arm curl (r=-0.427), sit-to-stand (r=-0.433), 6MWT (r=-0.421), IPAQ (r=-0.421), and WHOQOL-BREF (r=-0.538), all with p<0.005. In multiple regression, lower forced vital capacity (β=-0.360, p<0.001), lower WHOQOL-BREF scores (β=-0.302, p<0.001), higher fatigue severity (β=0.230, p=0.007), and lower 6MWT percentage of predicted distance (β=-0.165, p=0.023) independently predicted higher kinesiophobia. The model explained 60.3% of the variance (R²=0.603). These findings highlight the high prevalence and multi-dimensional impact of kinesiophobia in obstructive airway disease, emphasizing the importance of addressing fear of movement to improve physical activity, functional capacity, and quality of life in pulmonary rehabilitation settings.
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Platypnea-orthodeoxia syndrome (POS) is a rare condition with complex pathophysiology resulting from an anatomical site of shunting, mostly a patent foramen ovale (PFO), and factors promoting a right-to-left (R-L) shunt. A 54-year-old man was referred to our center for unexplained respiratory failure, exacerbated by sitting. A suspicion of POS was raised, and transesophageal echocardiography demonstrated a wide stretched PFO with R-L shunting, related to the presence of an aortic root aneurysm and right hemidiaphragm elevation, both compressing the right atrium, as well as a prominent eustachian valve. The patient underwent valve-sparing aortic root replacement and concomitant PFO closure, with resolution of symptoms. Multiple factors promoting R-L shunt have been associated with POS. The treatment of choice is represented by the correction of the anatomical shunt. Multidisciplinary team discussion is paramount for the diagnosis and management of this complex condition.
Long-term consequences of viral pneumonia on lung function depend on virus-specific tissue injury. Persistent impairment of alveolar-blood gas transport has been described after SARS-CoV-2 pneumonia but has not been investigated following respiratory syncytial virus (RSV) pneumonia. Possible long-term effects of these two viral infections were never compared after their clinical resolution in terms of lung physiology. The aim of this paper was to compare long-term sequelae of RSV and SARS-CoV-2 pneumonia on lung function and blood gas transport. Adults (>18 years) with previous RSV or SARS-CoV-2 pneumonia were investigated after complete computed tomography scan resolution. Collected variables included demographics, body mass index, hemoglobin, SpO₂, modified British Medical Research Council dyspnea score, spirometry, diffusing capacity [diffusing capacity for carbon oxide (DLCO), carbon monoxide transfer coefficient (KCO)], single-breath diffusing capacity for nitric oxide (DLNO) and DLCO, DLNO/DLCO ratio, and lung capillary blood volume (Vc). 38 post-SARS-CoV-2 and 37 post-RSV patients were studied. Groups were comparable and showed similar spirometric values. Compared with RSV, SARS-CoV-2 patients had significantly lower SpO₂, DLCO, and KCO (p<0.01). Vc was markedly reduced (p<0.001), with a corresponding increase in the DLNO/DLCO ratio (p<0.001). Only post-RSV patients were dyspnea-free. In conclusion, viral pneumonia may cause long-lasting lung function impairment depending on virus-specific tissue damage. Unlike RSV, SARS-CoV-2 pneumonia induces a persistent reduction of lung Vc, leading to impaired gas exchange despite radiological resolution.
Chronic Venous Insufficiency (CVI) is a complex condition resulting from venous valve dysfunction or a loss of structural integrity in the vein walls, affecting 60% of the general population. Although traditionally regarded as a localized peripheral pathology, emerging evidence suggests that CVI may serve as an early indicator of systemic vascular disease. Our comprehensive review aims to analyzes the pathophysiological links between CVI and global cardiovascular risk, evaluating the clinical impact of venous disease on cardiovascular morbidity and mortality. The current literature highlights shared mechanisms between CVI and arterial diseases, including chronic low-grade inflammation, oxidative stress, and endothelial dysfunction. Clinical studies indicate that CVI is an independent predictor of major adverse cardiovascular events (MACE) and all-cause mortality. CVI should be reinterpreted as a peripheral marker of systemic vascular frailty. The integration of proactive cardiovascular screening is proposed for the management of patients with advanced CVI to improve long-term prognosis and reduce the risk of fatal events.
Airway obstruction resulting from both malignant and non-malignant etiologies is a growing challenge in pulmonary diseases and critical care medicine, particularly after the COVID-19 pandemic. Conventional silicone and metallic airway stents may be indicated in airway obstructions that lead to palliative relief, but they may lead to complications such as migration, inflammatory reaction to the adjacent tissue, and granulation tissue overgrowth. We conducted this animal pilot study to investigate the biocompatibility of a next-generation nanocomposite silicone airway stent, engineered with 3wt% hydrophobic nano-silica reinforcement. Innovative characteristics of the stent include improved biocompatibility and reduced mucus adhesion due to its hydrophobic properties. A refined stenting technique was applied to implant the stent in the trachea of two sheep models by assembling two endotracheal tubes, Ambu, and the stent. After a two-month follow-up, high-resolution computed tomography imaging, 3D virtual bronchoscopy, bronchoscopy, and biopsy of the tracheal wall were done. Histopathologic assessment demonstrated an inflammatory infiltrate dominated by lymphocytes, without stromal reactions, mucosal and submucosal thickening, or granulation, confirming a favorable tissue tolerance. These preliminary outcomes emphasize the stent's potential as a transformative therapeutic option; however, the study's limited sample size and absence of comparative controls highlight the necessity for further preclinical trials with quantitative airflow parameters to elucidate the clinical translatability of this innovative biomaterial solution for airway obstructions. Additionally, the findings of this study can address the unmet needs in managing complex airway obstructions, particularly for patients refractory to current therapeutic options in the future.