Laboratory data and broncho-alveolar lavage on Covid-19 patients with no intensive care unit admission: Correlation with chest CT features and clinical outcomes.

Broncho-alveolar lavage (BAL) is indicated in cases of uncertain diagnosis but high suspicion of Sars-Cov-2 infection allowing to collect material for microbiological culture to define the presence of coinfection or super-infection. This prospective study investigated the correlation between chest computed tomography (CT) findings, Covid-19 Reporting and Data System score, and clinical outcomes in Coronavirus disease 2019 (Covid-19) patients who underwent BAL with the aim of predicting outcomes such as lung coinfection, respiratory failure, and hospitalization length based on chest CT abnormalities. Study population included 34 patients (range 38-90 years old; 20 males, 14 females) with a positive nucleic acid amplification test for Covid-19 infection, suitable BAL examination, and good quality chest CT scan in the absence of lung cancer history. Pulmonary coinfections were found in 20.6% of patients, predominantly caused by bacteria. Specific correlations were found between right middle lobe involvement and pulmonary co-infections. Severe lung injury (PaO2/FiO2 ratio of 100-200) was associated with substantial involvement of right middle, right upper, and left lower lobes. No significant correlation was found between chest CT findings and inflammatory markers (C-reactive protein, procalcitonin) or hospitalization length of stay. Specific chest CT patterns, especially in right middle lobe, could serve as indicators for the presence of co-infections and disease severity in noncritically ill Covid-19 patients, aiding clinicians in timely interventions and personalized treatment strategies.

Antiviral combination regimens as rescue therapy in immunocompromised hosts with persistent COVID-19.

The management of severe/prolonged SARS-CoV-2 infections in immunocompromised hosts is still challenging. We describe nine patients with hematologic malignancies with a history of unsuccessful SARS-CoV-2 treatment receiving antiviral combination treatment for persistent infection at a tertiary hospital in central Italy (University Hospital of Careggi, Florence). Combination treatments consisted of nirmatrelvir/ritonavir plus molnupiravir (n = 4), nirmatrelvir/ritonavir plus remdesivir (n = 4) or remdesivir plus molnupiravir (n = 1) for 10 days, in some cases associated with sotrovimab. Combinations were generally well tolerated. One patient obtained viral clearance but died due to the underlying disease. In eight cases, clinical and virological success was confirmed by radiological follow-up. Antivirals combination is likely to become a mainstay in the future management of COVID-19 among immunocompromised patients, but knowledge in this field is still very limited and prospective studies on larger cohorts are urgently warranted.

The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review.

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

Presentation and progression of MPO-ANCA interstitial lung disease.

The association between MPO-ANCA-associated vasculitis (AAV) and interstitial lung disease (ILD) has been well established. Pulmonary fibrosis may coexist with, follow, or even precede the diagnosis of AAV, and its presence adversely affects the prognosis. The optimal approach to investigating ANCA in patients with ILD remains a subject of ongoing debate. Here we aim to describe presentation and progression of MPO-ANCA ILD. We conducted a retrospective evaluation of a cohort of individuals diagnosed with MPO-ANCA ILD, with or without accompanying renal impairment, at the Immunology and Cell Therapy Unit, Careggi University Hospital, Florence, Italy, between June 2016 and June 2022. Clinical records, imaging studies, pathologic examinations, and laboratory test results were collected. Among the 14 patients identified with MPO-ANCA ILD, we observed a significant association between MPO-ANCA titers assessed at the time of ILD diagnosis and renal involvement. Renal impairment in these cases often manifested as subclinical or slowly progressive kidney damage. Interestingly, complement C3 deposits were consistently found in all renal biopsy specimens, thereby suggesting the potential for novel therapeutic targets in managing renal complications associated with MPO-ANCA ILD. The presentation of MPO-ANCA vasculitis as ILD can be the first and only clinical manifestation. MPO-ANCA levels at ILD diagnosis could warn on the progression to renal involvement in patients with MPO-ANCA ILD, hence caution is needed because renal disease can be subclinical or smoldering.

Utility of bronchoalveolar lavage for COVID-19: a perspective from the Dragon consortium.

Diagnosing COVID-19 and treating its complications remains a challenge. This review reflects the perspective of some of the Dragon (IMI 2-call 21, #101005122) research consortium collaborators on the utility of bronchoalveolar lavage (BAL) in COVID-19. BAL has been proposed as a potentially useful diagnostic tool to increase COVID-19 diagnosis sensitivity. In both critically ill and non-critically ill COVID-19 patients, BAL has a relevant role in detecting other infections or supporting alternative diagnoses and can change management decisions in up to two-thirds of patients. BAL is used to guide steroid and immunosuppressive treatment and to narrow or discontinue antibiotic treatment, reducing the use of unnecessary broad antibiotics. Moreover, cellular analysis and novel multi-omics techniques on BAL are of critical importance for understanding the microenvironment and interaction between epithelial cells and immunity, revealing novel potential prognostic and therapeutic targets. The BAL technique has been described as safe for both patients and healthcare workers in more than a thousand procedures reported to date in the literature. Based on these preliminary studies, we recognize that BAL is a feasible procedure in COVID-19 known or suspected cases, useful to properly guide patient management, and has great potential for research.

The Performance of Pulmonary Function Tests in Predicting Systemic Sclerosis-Interstitial Lung Disease in the European Scleroderma Trial and Research Database.

BACKGROUND AND OBJECTIVES: In SSc, ILD is a major cause of morbidity and mortality. We aimed to investigate the performance of DLCO (diffusing capacity of lung carbon monoxide) and FVC (forced vital capacity) delta change (Δ) and baseline values in predicting the development of SSc-ILD. METHODS: Longitudinal data of DLCO, FVC, and ILD on the HRCT of SSc patients from the EUSTAR database were evaluated at baseline (t0) and after 12 (±4) (t1) and 24 (±4) (t2) months. RESULTS: 474/17805 patients were eligible for the study (403 females); 46 (9.7%) developed ILD at t2. Positivity for anti-topoisomerase antibodies (117 patients) showed an association with ILD development at t2 (p = 0.0031). Neither the mean t0 to t1 change (Δ) of DLCO nor the mean t0 to t1 FVCΔ predicted the appearance of ILD at t2. Investigating the possible role of baseline DLCO and FVC values in predicting ILD appearance after 24 (±4) months, we observed a moderate predictive capability of t0 DLCO < 80%, stronger than that of FVC < 80%. CONCLUSIONS: We suggest that an impaired baseline DLCO may be predictive of the appearance of ILD after 2 years of follow-up. This result advances the hypothesis that a reduction in gas exchange may be considered an early sign of lung involvement. However, further rigorous studies are warranted to understand the predictive role of DLCO evaluation in the course of SSc.

Images in Sarcoidosis: new section of our Journal.

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Doubts and concerns about COVID-19 uncertainties on imaging data, clinical score, and outcomes.

BACKGROUND: COVID-19 is a pandemic disease affecting predominantly the respiratory apparatus with clinical manifestations ranging from asymptomatic to respiratory failure. Chest CT is a crucial tool in diagnosing and evaluating the severity of pulmonary involvement through dedicated scoring systems. Nonetheless, many questions regarding the relationship of radiologic and clinical features of the disease have emerged in multidisciplinary meetings. The aim of this retrospective study was to explore such relationship throughout an innovative and alternative approach. MATERIALS AND METHODS: This study included 550 patients (range 25-98 years; 354 males, mean age 66.1; 196 females, mean age 70.9) hospitalized for COVID-19 with available radiological and clinical data between 1 March 2021 and 30 April 2022. Radiological data included CO-RADS, chest CT score, dominant pattern, and typical/atypical findings detected on CT examinations. Clinical data included clinical score and outcome. The relationship between such features was investigated through the development of the main four frequently asked questions summarizing the many issues arisen in multidisciplinary meetings, as follows 1) CO-RADS, chest CT score, clinical score, and outcomes; 2) the involvement of a specific lung lobe and outcomes; 3) dominant pattern/distribution and severity score for the same chest CT score; 4) additional factors and outcomes. RESULTS: 1) If CT was suggestive for COVID, a strong correlation between CT/clinical score and prognosis was found; 2) Middle lobe CT involvement was an unfavorable prognostic criterion; 3) If CT score < 50%, the pattern was not influential, whereas if CT score > 50%, crazy paving as dominant pattern leaded to a 15% increased death rate, stacked up against other patterns, thus almost doubling it; 4) Additional factors usually did not matter, but lymph-nodes and pleural effusion worsened prognosis. CONCLUSIONS: This study outlined those radiological features of COVID-19 most relevant towards disease severity and outcome with an innovative approach.