Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Synthesis and characterization of some lanthanoid complexes of salicylaldehyde salicyloyl hydrazone

1146-1151Some lanthanoid complexes of the types, [Ln(ssh)( H2O)n].H2O and [Ln'(Hssh)(X)(H2O)3].H2O , where Ln = Y, La, Nd, Gd, Tb and Dy; Ln' = Pr/Sm for X = NO3 /Cl and H3ssh = salicylaldehyde salicyloyl hydrazone, have been synthesized and characterized by elemental analyses, molar conductance, magnetic susceptibility, infrared, electronic and 1H NMR spectral data. Selected complexes have also been studied on the basis of their solid state electrical conductivity, band gap, and powder X-ray diffraction data. The complexes, except those of the Pr and Sm, are polymeric in nature showing high decomposition points. Dehydration study indicates the presence of water molecules both in the lattice and coordination sphere of the complex metal ions. IR and 1H NMR spectral data suggest trinegative tetradentate and dinegative tridentate coordination of H3ssh in the complexes. The chloro and nitrato groups are found to coordinate to the metal ion as monodentate and bidentate-chelating species respectively. Solid state electrical conductivity data at various frequencies show semi-conducting nature of the complexes. Optical band gap studies show the complex [Gd(ssh)(H2O)3].H2O to be a direct band gap semi-conducting material with a band gap of 2.64 eV. Powder X-ray diffraction patterns show orthorhombic structure for most of the complexes. Various polyhedral geometries such as distorted octahedron, pentagonal bipyramid and distorted square antiprism are tentatively proposed for the complexes.</span

Hypothyroidism in Carcinoma of the Tongue with Adjuvant Treatment

Objective The objective of this study was to evaluate the incidence of hypothyroidism with adjuvant treatment in oral tongue carcinoma patients treated primarily with surgery. Materials and methods A retrospective review was carried out to analyze hypothyroidism incidence and its relation to adjuvant treatment (radiation/radio-chemotherapy) in oral tongue carcinoma after the primary surgical ablation and neck dissection. Hypothyroidism was analyzed in relation with dose of radiation, gender, and adjuvant treatment modality. Results The study analyzed the patients who were treated between January 2012 and June 2015. Among 705 patients with carcinoma of the tongue treated primarily with wide local excision and neck dissection, 383 received adjuvant treatment. A total of 215 patients received radiation, and 168 received concurrent radio-chemotherapy. Of 378 patients, 78 developed hypothyroidism during follow-up: 27 patients received concurrent radio-chemotherapy, and the remaining 51 received only radiation. Lower neck received 40–48 Gy in 2 patients, 50 Gy in 74 patients, and 60–70 Gy and concurrent radio-chemotherapy in 27 patients. Median follow-up was 32 months. Hypothyroidism occurred in 21.5% of patients with squamous cell carcinoma of the oral tongue. The minimum period to develop hypothyroidism was 3 months in this study. Gender and adjuvant treatment were not found to be significant for the incidence of hypothyroidism. Conclusions A significant number of patients with carcinoma of the tongue who receive adjuvant treatment will develop hypothyroidism, hence frequent monitoring of thyroid function is advised during follow-up