Management of interstitial lung disease (ILD) in myositis syndromes: A practical guide for clinicians

Inflammatory myopathies are heterogeneous clinico-serological syndromes, with variable clinical manifestations. Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with myositis. The clinical manifestation of myositis-ILD is heterogeneous, e.g., with acute-on-chronic presentations, as well as the chronic aftermath of acute disease. Here, we have largely divided myositis-ILD into three main prognostic groups which require different treatment approaches: mild-moderate (subacute), severe or progressive (acute or subacute) and rapidly progressive, life-threatening. In current clinical practice, the treatment of myositis-ILD involves immunomodulation in an induction-maintenance treatment paradigm. There is now an option to add antifibrotics to slow the progression of established fibrosis in selected cases with chronic progressive phenotype. Here, we describe current concepts in myositis-ILD and aim to provide a practical guide for clinicians on how to approach assessment, including early identification of ILD, phenotyping of patients according to clinical trajectory and likely prognosis and stratified management adopting multi-disciplinary cross-speciality expertise, with close collaboration between rheumatology and respiratory physicians

A combined microfinance and training intervention can reduce HIV risk behaviour in young female participants.

OBJECTIVE: To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa. DESIGN: : Secondary analysis of quantitative and qualitative data from a cluster randomized trial, the Intervention with Microfinance for AIDS and Gender Equity study. METHODS: Eight villages were pair-matched and randomly allocated to receive the intervention. At baseline and after 2 years, HIV risk behavior was assessed among female participants aged 14-35 years. Their responses were compared with women of the same age and poverty group from control villages. Intervention effects were calculated using adjusted risk ratios employing village level summaries. Qualitative data collected during the study explored participants' responses to the intervention including HIV risk behavior. RESULTS: After 2 years of follow-up, when compared with controls, young participants had higher levels of HIV-related communication (adjusted risk ratio 1.46, 95% confidence interval 1.01-2.12), were more likely to have accessed voluntary counseling and testing (adjusted risk ratio 1.64, 95% confidence interval 1.06-2.56), and less likely to have had unprotected sex at last intercourse with a nonspousal partner (adjusted risk ratio 0.76, 95% confidence interval 0.60-0.96). Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality. Although women noted challenges associated with acceptance of condoms by men, increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships. CONCLUSIONS: In addition to impacts on economic well being, women's empowerment and intimate partner violence, interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior

Ovarian carcinosarcoma is highly aggressive compared to other ovarian cancer histotypes

Background: Ovarian carcinosarcoma (OCS) is an unusual ovarian cancer type characterized by distinct carcinomatous and sarcomatous components. OCS has been excluded from many of the pan-histotype studies of ovarian carcinoma, limiting our understanding of its behavior.Methods: We performed a multi-cohort cross-sectional study of characteristics and outcomes in ovarian cancer patients from Scotland (n=2082) and the Surveillance, Epidemiology and End Results Program (SEER, n=44946) diagnosed with OCS or one of the other major histotypes: high grade serous (HGSOC), endometrioid (EnOC), clear cell (CCOC), mucinous (MOC) or low grade serous ovarian carcinoma (LGSOC). Differences in overall survival were quantified using Cox regression models to calculate hazard ratios (HR).Results: Across both cohorts, OCS patients were significantly older at diagnosis compared to all other histotypes (median age at diagnosis 69 and 67 in Scottish and SEER cohorts) and demonstrated the shortest survival time upon univariable analysis. Within the Scottish cohort, 59.3% and 16.9% of OCS patients presented with FIGO stage III and IV disease, respectively; this was significantly higher than in EnOC, CCOC or MOC (P<0.0001 for all), but lower than in HGSOC (P=0.004). Multivariable analysis accounting for other prognostic factors identified OCS as independently associated with significantly shorter survival time compared to HGSOC, EnOC, LGSOC and MOC in both the Scottish (multivariable HR vs OCS: HGSOC 0.45, EnOC 0.39, LGSOC 0.26, MOC 0.43) and SEER cohorts (multivariable HR vs OCS: HGSOC 0.59, EnOC 0.34, LGSOC 0.30, MOC 0.81). Within the SEER cohort, OCS also demonstrated shorter survival compared to CCOC (multivariable HR 0.63, 95% CI 0.58-0.68), but this was not replicated within the Scottish cohort (multivariable HR for CCOC: 1.05, 95% CI 0.74-1.51). Within early-stage disease specifically (FIGO I-II or SEER localized stage), OCS was associated with the poorest survival of all histotypes across both cohorts. In the context of late-stage disease (FIGO III-IV or SEER distant stage), OCS, MOC and CCOC represented the histotypes with poorest survival.Conclusion: OCS is a unique ovarian cancer type that affects older women and is associated with exceptionally poor outcome, even when diagnosed at earlier stage. New therapeutic options are urgently required to improve outcomes

Integrin α2β1 Expression Regulates Matrix Metalloproteinase-1-Dependent Bronchial Epithelial Repair in Pulmonary Tuberculosis.

Pulmonary tuberculosis (TB) is caused by inhalation of Mycobacterium tuberculosis, which damages the bronchial epithelial barrier to establish local infection. Matrix metalloproteinase-1 plays a crucial role in the immunopathology of TB, causing breakdown of type I collagen and cavitation, but this collagenase is also potentially involved in bronchial epithelial repair. We hypothesized that the extracellular matrix (ECM) modulates M. tuberculosis-driven matrix metalloproteinase-1 expression by human bronchial epithelial cells (HBECs), regulating respiratory epithelial cell migration and repair. Medium from monocytes stimulated with M. tuberculosis induced collagenase activity in bronchial epithelial cells, which was reduced by ~87% when cells were cultured on a type I collagen matrix. Matrix metalloproteinase-1 had a focal localization, which is consistent with cell migration, and overall secretion decreased by 32% on type I collagen. There were no associated changes in the specific tissue inhibitors of metalloproteinases. Decreased matrix metalloproteinase-1 secretion was due to ligand-binding to the α2β1 integrin and was dependent on the actin cytoskeleton. In lung biopsies, samples from patients with pulmonary TB, integrin α2β1 is highly expressed on the bronchial epithelium. Areas of lung with disrupted collagen matrix showed an increase in matrix metalloproteinases-1 expression compared with areas where collagen was comparable to control lung. Type I collagen matrix increased respiratory epithelial cell migration in a wound-healing assay, and this too was matrix metalloproteinase-dependent, since it was blocked by the matrix metalloproteinase inhibitor GM6001. In summary, we report a novel mechanism by which α2β1-mediated signals from the ECM modulate matrix metalloproteinase-1 secretion by HBECs, regulating their migration and epithelial repair in TB

Interstitial lung disease:A review of classification, aetiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment

IInterstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases

The survival benefit associated with complete macroscopic resection in epithelial ovarian cancer is histotype-specific

Background: Complete macroscopic resection (CMR) is a key factor associated with prolonged survival in ovarian cancer. However, most evidence derives from high grade serous ovarian carcinoma (HGSOC), and the benefit of CMR in other histotypes is poorly characterised. We sought to determine which histotypes derive the greatest benefit from CMR to better inform future decisions on radical cytoreductive efforts. Methods: We performed multivariable analysis of disease-specific survival (DSS) across two independent patient cohorts to determine the magnitude of benefit associated with CMR within each histotype. Results: Across both cohorts (Scottish, n=1622; SEER, n=18947), CMR was associated with prolonged DSS; this was more marked in the Scottish cohort (multivariable HR 0.44, 95%CI 0.37-0.52 vs 0.59, 95%CI 0.57-0.62 in SEER). In both cohorts, clear cell ovarian carcinoma (CCOC) was among the histotypes to benefit most from CMR (multivariable HR 0.23 and 0.50 in Scottish and SEER cohorts); HGSOC cases demonstrated highly significant and clinically meaningful survival benefit, but this was of lower magnitude than in CCOC and endometrioid ovarian carcinoma (EnOC) across both cohorts. The benefit derived in low grade serous ovarian carcinoma is also high (multivariable HR 0.27 in Scottish cohort). CMR was associated with prolonged survival in mucinous ovarian carcinoma (MOC) patients in the SEER cohort (multivariable HR 0.65), but the associated failed to reach statistical significance in the Scottish cohort. Conclusions: The overall ovarian cancer patient population demonstrates significant survival benefit associated with CMR; however, the magnitude of benefit differs between histotypes. <br/

Home monitoring of physiology and symptoms to detect interstitial lung disease exacerbations and progression:a systematic review

Background: Acute exacerbations (AEs) and disease progression in interstitial lung disease (ILD) pose important challenges to clinicians and patients. AEs of ILD are variable in presentation but may result in rapid progression of ILD, respiratory failure and death. However, in many cases AEs of ILD may go unrecognised so that their true impact and response to therapy is unknown. The potential for home monitoring to facilitate early, and accurate, identification of AE and/or ILD progression has gained interest. With increasing evidence available, there is a need for a systematic review on home monitoring of patients with ILD to summarise the existing data. The aim of this review was to systematically evaluate the evidence for use of home monitoring for early detection of exacerbations and/or progression of ILD. Method: We searched Ovid-EMBASE, MEDLINE and CINAHL using Medical Subject Headings (MeSH) terms in accordance with the PRISMA guidelines (PROSPERO registration number CRD42020215166). Results: 13 studies involving 968 patients have demonstrated that home monitoring is feasible and of potential benefit in patients with ILD. Nine studies reported that mean adherence to home monitoring was &gt;75%, and where spirometry was performed there was a significant correlation (r=0.72–0.98, p&lt;0.001) between home and hospital-based readings. Two studies suggested that home monitoring of forced vital capacity might facilitate detection of progression in idiopathic pulmonary fibrosis. Conclusion: Despite the fact that individual studies in this systematic review provide supportive evidence suggesting the feasibility and utility of home monitoring in ILD, further studies are necessary to quantify the potential of home monitoring to detect disease progression and/or AEs.</p

Evaluating a Remote Monitoring Program for Respiratory Diseases: Prospective Observational Study

BACKGROUND: Patients with chronic respiratory diseases and those in the postdischarge period following hospitalization because of COVID-19 are particularly vulnerable, and little is known about the changes in their symptoms and physiological parameters. Continuous remote monitoring of physiological parameters and symptom changes offers the potential for timely intervention, improved patient outcomes, and reduced health care costs. OBJECTIVE: This study investigated whether a real-time multimodal program using commercially available wearable technology, home-based Bluetooth-enabled spirometers, finger pulse oximeters, and smartphone apps is feasible and acceptable for patients with chronic respiratory diseases, as well as the value of low-burden, long-term passive data collection. METHODS: In a 3-arm prospective observational cohort feasibility study, we recruited 60 patients from the Royal Free Hospital and University College Hospital. These patients had been diagnosed with interstitial lung disease, chronic obstructive pulmonary disease, or post-COVID-19 condition (n=20 per group) and were followed for 180 days. This study used a comprehensive remote monitoring system designed to provide real-time and relevant data for both patients and clinicians. Data were collected using REDCap (Research Electronic Data Capture; Vanderbilt University) periodic surveys, Remote Assessment of Disease and Relapses-base active app questionnaires, wearables, finger pulse oximeters, smartphone apps, and Bluetooth home-based spirometry. The feasibility of remote monitoring was measured through adherence to the protocol, engagement during the follow-up period, retention rate, acceptability, and data integrity. RESULTS: Lowest-burden passive data collection methods, via wearables, demonstrated superior adherence, engagement, and retention compared with active data collection methods, with an average wearable use of 18.66 (SD 4.69) hours daily (77.8% of the day), 123.91 (SD 33.73) hours weekly (72.6% of the week), and 463.82 (SD 156.70) hours monthly (64.4% of the month). Highest-burden spirometry tasks and high-burden active app tasks had the lowest adherence, engagement, and retention, followed by low-burden questionnaires. Spirometry and active questionnaires had the lowest retention at 0.5 survival probability, indicating that they were the most burdensome. Adherence to and quality of home spirometry were analyzed; of the 7200 sessions requested, 4248 (59%) were performed. Of these, 90.3% (3836/4248) were of acceptable quality according to American Thoracic Society grading. Inclusion of protocol holidays improved retention measures. The technologies used were generally well received. CONCLUSIONS: Our findings provide evidence supporting the feasibility and acceptability of remote monitoring for capturing both subjective and objective data from various sources for respiratory diseases. The high engagement level observed with passively collected data suggests the potential of wearables for long-term, user-friendly remote monitoring in respiratory disease management. The unique piloting of certain features such as protocol holidays, alert notifications for missing data, and flexible support from the study team provides a reference for future studies in this field. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/28873