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Complete prosthetic replacement does not increase overall postoperative morbidity in patients undergoing SVC resection and can be safely performed when other reconstruction techniques preclude sufficient tumour-free resection margin or compromise adequate blood flow.

Background and purpose: This phase 1 trial aimed to determine the maximum tolerated dose (MTD; primary objective) of a p38-MAPK inhibitor, ralimetinib, with radiotherapy (RT) and chemotherapy (TMZ), in the treatment of newly diagnosed glioblastoma (GBM) patients.Materials and methods: The study was designed as an open-label dose-escalation study driven by a Tite-CRM design and followed by an expansion cohort. Ralimetinib was administered orally every 12 hours, 7 days a week, for 2 cycles of 2 weeks at a dose of 100, 200 or 300 mg/12h. Patients received ralimetinib added to standard concurrent RT (60 Gy in 30 fractions) with TMZ (75 mg/m²/day) and 6 cycles of adjuvant TMZ (150 to 200 mg/m² on days 1 to 5 every 28 days).Results: The MTD of ralimetinib was 100 mg/12h with chemoradiotherapy. The three patients treated at 200 mg/12h presented a dose-limiting toxicity: one patient had a grade 3 face edema, and two patients had a grade 3 rash and grade 3 hepatic cytolysis (66%). Of the 18 enrolled patients, 15 received the MTD of ralimetinib. At the MTD, the grade ≥ 3 adverse events during concomitant chemoradiotherapy were hepatic cytolysis (2/15 patients), dermatitis/rash (1/15), lymphopenia (1/15) and nausea/vomiting (1/15). No interaction of TMZ and ralimetinib when administrated concomitantly has been observed.Inhibition of pMAPKAP-K2 (-54%) was observed in peripheral blood mononuclear cells. Conclusion:This phase 1 trial is the first trial to study the combination of a p38-MAPK inhibitor, ralimetinib, with radiotherapy (RT) and chemotherapy (TMZ), in the treatment of newly diagnosed glioblastoma (GBM) patients. The MTD of ralimetinib was 100 mg/12h. The most frequent doselimiting toxicities were hepatic cytolysis and rash.

Background Spontaneous pneumothorax has been reported as a possibile complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaeous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. An insight on pathological finding is given. Case presentation Two patients presented to our hospital with spontaneous pneumothorax associated with Sars-Cov2 infection onset. After initial conservative treatment with chest drain, both patients had a recurrence of pneumothorax during COVI-19 disease, contralateral (patient 1) or ipsilateral (patient 2) and therefore underwent lung surgery with thoracoscopy and bullectomy. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding. Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thicknening of vessels with blood extravasation and microthrombi. Conclusions Although rarely, COVID-19 may present with spontaneous pneumothorax. Lung surgery for pneumothorax in COVID-19 patients can be safely and effectively performed when necessary.

Spontaneous pneumothorax has been reported as a possibile complication of novel coronavirus associated pneumonia (COVID-19). We report two cases of COVID-19 patients who developed spontaeous and recurrent pneumothorax as a presenting symptom, treated with surgical procedure. Intraoperative findings of COVID-19 pneumonia were parenchymal atelectasis and vascular congestion. Lung tissue was very frail and prone to bleeding. Histological examination showed interstitial infiltration of lymphocytes and plasma cells, as seen in non specific interstitial pneumonia, together with myo-intimal thicknening of vessels with blood extravasation and microthrombi. Lung surgery for pneumothorax in COVID-19 patients can be safely and effectively performed when necessary.