Prolonged-release pirfenidone in patients with pulmonary fibrosis as a phenotype of post-acute sequelae of COVID-19 pneumonia. Safety and efficacy.

INTRODUCTION: One of the major concerns with post-acute sequelae of COVID-19 (PASC) is the development of pulmonary fibrosis, for which no approved pharmacological treatment exists. Therefore, the primary aim of this open-label study was to evaluate the safety and the potential clinical efficacy of a prolonged-release pirfenidone formulation (PR-PFD) in patients having PASC-pulmonary fibrosis. METHODS: Patients with PASC-pulmonary fibrosis received PR-PFD 1800 mg/day (1200 mg in the morning after breakfast and 600 mg in the evening after dinner) for three months. Blood samples were taken to confirm the pharmacokinetics of PR-PFD, and adverse events (AEs) were evaluated monthly using a short questionnaire. Symptoms, dyspnea, and pulmonary function tests (spirometry, diffusing capacity for carbon monoxide, plethysmography, and 6-min walk test [6MWT]) were evaluated at baseline, and one and three months after having started the PR-PFD treatment. RESULTS: Seventy subjects with mild to moderate lung restriction were included. The most common AEs were diarrhea (23%), heartburn (23%), and headache (16%), for which no modifications in the drug study were needed. Two patients died within the first 30 days of enrolment, and three opted not to continue the study, events which were not associate with PR-PFD. Pulmonary function testing, 6MWT, dyspnea, symptoms, and CT scan significantly improved after three months of treatment with PR-PFD. CONCLUSION: In patients with PASC pulmonary fibrosis, three months' treatment with PR-PFD was safe and showed therapeutic efficacy. Still, it remains to be seen whether the pulmonary fibrotic process remains stable, becomes progressive or will improve.

Immediate changes in intra-abdominal pressure and lung indicators in patients undergoing complex ventral hernia repair with the transversus abdominis muscle release, with and without preoperative botulinum toxin.

PURPOSE: The current treatment of complex ventral hernias involves muscle closure with components separation techniques and mesh placement. The purpose of this study is to evaluate the immediate postoperative changes in the intra-abdominal pressure (IAP), and lung indicators after treatment of complex ventral hernias with the transversus abdominis reléase (TAR) technique. METHODS: All patients with complex ventral hernias treated between November 28th, 2016 and October 6th, 2021 were initially included. We excluded patients with lung and/or heart comorbidities. A total of 43 patients were studied, measuring IAP, lung compliance, pulmonary plateau pressure (PPP), and end-tidal CO2 before and after surgical treatment. RESULTS: Median IAP increased from 5 to 9 mmHg (p < 0.0001), and PPP from 11 to 12 mmHg (p = 0.004). Increased body mass index (BMI) was associated to a PPP increase above normal values. Postoperative changes were not different in patients receiving preoperative preparation with botulinum toxin. CONCLUSION: After complex ventral hernia closure, there is an immediate impact on IAP and PPP, the latter more frequent in patients with the highest BMI, and this may not be prevented by the preoperative administration of botulinum toxin.