H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

Risk factors for nosocomial COVID-19 in a French university hospital.

OBJECTIVES: Prevention strategies implemented by hospitals to reduce nosocomial transmission of SARS-CoV-2 sometimes failed. Our aim was to determine the risk factors for nosocomial COVID-19. PATIENTS AND METHODS: A case-control study was conducted (September 1, 2020-January 31, 2021) with adult patients hospitalized in medical or surgical units. Infants or patients hospitalized in ICU were excluded. Cases were patients with nosocomial COVID-19 (clinical symptoms and RT-PCR + for SARS-CoV-2 or RT-PCR + for SARS-CoV-2 with Ct ≤ 28 more than 5 days after admission); controls were patients without infection (RT-PCR- for SARS-CoV-2 > 5 days after admission). They were matched according to length of stay before diagnosis and period of admission. Analyses were performed with a conditional logistic regression. RESULTS: A total of 281 cases and 441 controls were included. In the bivariate analysis, cases were older (OR per 10 years: 1.22; 95%CI [1.10;1.36]), had more often shared a room (OR: 1.74; 95%CI [1.25;2.43]) or a risk factor for severe COVID-19 (OR: 1.94; 95%CI [1.09;3.45]), were more often hospitalized in medical units [OR: 1.59; 95%CI [1.12;2.25]), had higher exposure to contagious health care workers (HCW; OR per 1person-day: 1.12; 95%CI [1.08;1.17]) and patients (OR per 1 person-day: 1.11; 95%CI [1.08;1.14]) than controls. In an adjusted model, risk factors for nosocomial COVID-19 were exposure to contagious HCW (aOR per 1person-day: 1.08; 95%CI [1.03;1.14]) and to contagious patients (aOR per 1person-day: 1.10; 95%CI [1.07;1.13]). CONCLUSIONS: Exposure to contagious professionals and patients are the main risk factors for nosocomial COVID-19.

Assessing the incidence of nerve injuries according to different mandibular osteotomies including Wing osteotomies.

We use currently 3 types of new mandibular osteotomies (a shortened Bilateral Sagittal Split Osteotomy (BSSO), associated or not with Chin Wing or Mini Wing). Chin osteotomy is a modified genioplasty extended along the basilar border and the angles of the mandible. These osteotomies are associated with a risk of inferior alveolar nerve (IAN) damage. We prospectively studied 113 consecutive patients operated on by the same surgeon who underwent one of the following procedures: (1) isolated BSSO, (2) BSSO with a Chin Wing, (3) BSSO with a Mini Wing, (4) isolated Chin Wing. We analyzed rates of IAN damage and impact on the patients' life by using a subjective questionnaire administered at the patient's 1 year follow up appointment between June 2018 and August 2019. Sixty-seven patients underwent isolated BSSO, 24 BSSO with Mini Wing, 13 BSSO with Chin Wing, and 9 Chin Wing only. Our analysis reveals that nerve damage is greater in the BSSO group associated with Chin Wing (50% vs. 21.6%; p=0.006). However, there is no significant difference between nerve damage in the Mini wing group and the isolated BSSO group (27.1% vs. 21.6%; p=0.432). In the isolated Chin Wing group, the inferior alveolar nerve damage rate was 11%. There is no significant difference between the groups with regard to the impact of the nerve damage on the patients' life. In case of BSSO with concomitant Wing osteotomy, we conclude that Mini Wing osteotomies cause less nerve related morbidity than Chin Wing.

Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules.

BACKGROUND: RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules. METHODS: We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated. RESULTS: Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date. CONCLUSION: Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.