BackgroundSurvivors of severe-to-critical COVID-19 may have functional impairment, radiological sequelae and persistent symptoms requiring prolonged follow-up. This pragmatic study aimed to describe their clinical follow-up and determine their respiratory recovery trajectories, and factors that could influence them and their health-related quality of life.MethodsAdults hospitalised for severe-to-critical COVID-19 were evaluated at 3 months and up to 12 months post-hospital discharge in this prospective, multicentre, cohort study.ResultsAmong 485 enrolled participants, 293 (60%) were reassessed at 6 months and 163 (35%) at 12 months; 89 (51%) and 47 (27%) of the 173 ones initially managed with standard oxygen were reassessed at 6 and 12 months, respectively. At 3 months, 34%, 70% and 56% of the participants had a restrictive lung defect, impaired DLCOand significant radiological sequelae, respectively. During extended follow-up, DLCOand FVC (% of predicted value) increased by means of +4 points at 6 months, and +6 points at 12 months. Sex, body mass index, chronic respiratory disease, immunosuppression, pneumonia extent or corticosteroid use during acute COVID-19 and prolonged invasive mechanical ventilation (IMV) were associated with DLCOat month 3, but not its trajectory thereafter. Among 475 (98%) patients with at least one chest computed-tomography scan during follow-up, 196 (41%) had significant sequelae on their last images.ConclusionAlthough pulmonary function and radiological abnormalities improved up to 1 year post-acute-COVID-19, high percentages of severe-to-critical disease survivors, including a notable proportion of those managed with standard oxygen, had significant lung sequelae and residual symptoms justifying prolonged follow-up.

Backgrounds: Malignant pleural mesothelioma (MPM) is a cancer with poor prognosis. Second-line and onward therapy has many options, including immune-checkpoint inhibitors with demonstrated efficacy: 10–25% objective response rate (ORR) and 40–70% disease-control rate (DCR) in clinical trials on selected patients. This study evaluated real-life 2L+ nivolumab efficacy in MPM patients and looked for factors predictive of response. Methods: This retrospective study included (September 2017–July 2021) all MPM patients managed in 11 French centers. Results: The 109 enrolled patients’ characteristics were: median age: 69 years; 67.9% men; 82.6% epithelioid subtype. Strictly, second-line nivolumab was given to 51.4%. Median PFS and OS were 3.8 (3.2–5.9) and 12.8 (9.2–16.4) months. ORR was 17/109 (15.6%); 34/109 patients had a stabilized disease (DCR 46.8%). Univariable analysis identified several parameters as significantly (p < 0.05) prognostic of OS [HR (95% CI)]: biphasic subtype: 3.3 (1.52–7.0), intermediate Lung Immune Prognostic Index score: 0.46 (0.22–0.99), progression on the line preceding nivolumab: 2.1 (1.11–3.9) and age > 70 years: 2.5 (1.5–4.0). Multivariable analyses retained only biphasic subtype: 3.57 (1.08–11.8) and albumin < 25 g/L: 10.28 (1.5–70.7) as significant and independent predictors. Conclusions: Second-line and onward nivolumab is effective against MPM in real life but with less effectiveness in >70 years. Ancillary studies are needed to identify the predictive factors.

No abstract

Background: The association of different parathymic entities is common in thymic epithelial tumors (TETs), although only anecdotal case reports of TET patients exhibiting both pure red cell aplasia (PRCA) and Good Syndrome (GS) were described to date. We prospectively evaluated the outcomes of TET patients with PRCA and GS treated with combination therapy allowing prolonged control of TET, autoimmunity (PRCA) and immunodeficiency (GS).Methods: From 2013 consecutive TET patients, treated at Rare Tumors Reference Center of University Federico II, underwent diagnostic work-up for GS and PRCA, in the presence of suspicious symptoms. Subjects with GS who developed also PRCA were treated with a multi-agent therapy, including long acting octreotide 30 mg i.m. every 4 weeks, prednisone 0.6-1 mg/kg/daily (tapered when reaching Hb > 13 g/dl), cyclosporine escalation dose 50 to 200 mg/daily, darbepoietin 150 mcg weekly, intravenous immunoglobulin at 500 mg/kg per day for 5 days/monthly (tapered to 30 gr every 4 weeks), cotrimoxazolo antibiotic prophylaxis. Reticulocytes, serum immunoglobulin, C reactive protein (CRP), and Hb levels were closely monitored. Immunophenotype was assessed on whole blood by 8-colour immunophenotyping kit and Treg detection kit (CD4/CD25/CD127). TET Time to progression (TET-TTP), PRCA remission (PRCA-R), as well as occurrence of life treating infections, were assessed.Results: 16 patients were included in this study. Median age was 44 years (range 33-65); male/female ratio was 1/1; the most frequent histotype was B2 thymoma (57%). Prolonged PRCA-R was observed in all but one patient, with median time to PRCA-R of 40 days. Correlation between increase of reticulocytes and circulating Treg was detected (p ¼ 0.0003). At the time of the last follow-up, 15 patients were alive; 2 had PRCA recurrence after a median of 2 years from the initial diagnosis, one patient died for fatal medullary aplasia and 2 were hospitalized for staphylococcus pneumonitis. Median TET-TTP of 11 months was registered.Conclusions: This is the largest series of TET patients with PRCA and GS ever reported. The proposed multi-agent therapy achieved fast and prolonged PRCA-R, prolonged TET control and low rate of life treating infectious complications.Legal entity responsible for the study: CRCTR Rare Tumors Reference Center of Campania Region.

No abstract