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Immune checkpoint inhibitors (ICIs) reinvigorate anti-tumor immune responses by disrupting co-inhibitory immune checkpoint molecules such as programmed cell death 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4). Although ICIs have had unprecedented success and have become the standard of care for many cancers, they are often accompanied by off-target inflammation that can occur in any organ system. These immune related adverse events (irAEs) often require steroid use and/or cessation of ICI therapy, which can both lead to cancer progression. Although irAEs are common, the detailed molecular and immune mechanisms underlying their development are still elusive. To further our understanding of irAEs and develop effective treatment options, there is pressing need for preclinical models recapitulating the clinical settings. In this review, we describe current preclinical models and immune implications of ICI-induced skin toxicities, colitis, neurological and endocrine toxicities, pneumonitis, arthritis, and myocarditis along with their management.

Although most follicular-derived thyroid cancers are well differentiated and have an overall excellent prognosis following treatment with surgery and radioiodine, management of advanced thyroid cancers, including iodine refractory disease and poorly differentiated/undifferentiated subtypes, is more challenging. Over the past decade, better understanding of the genetic drivers and immune milieu of advanced thyroid cancers has led to significant progress in the management of these patients. Numerous targeted kinase inhibitors are now approved by the U.S Food and Drug administration (FDA) for the treatment of advanced, radioiodine refractory differentiated thyroid cancers (DTC) as well as anaplastic thyroid cancer (ATC). Immunotherapy has also been thoroughly studied and has shown promise in selected cases. In this review, we summarize the progress in the understanding of the genetic landscape and the cellular and molecular basis of radioiodine refractory-DTC and ATC, as well as discuss the current treatment options and future therapeutic avenues.

A 32-year-old man presented with a 10-day history of fever, chills, nausea, vomiting, myalgia, nonproductive cough, and worsening dyspnea after freshwater swimming in the Caribbean 1 week prior to presentation. Shortly after arrival at the hospital, the patient developed severe respiratory distress with massive hemoptysis. Based on serologic workup, he was diagnosed with leptospirosis pulmonary hemorrhage syndrome leading to diffuse alveolar hemorrhage, severe hypoxemic respiratory failure, and multiorgan failure. He received appropriate antibiotic coverage along with hemodynamic support with norepinephrine and vasopressin, mechanical ventilation, and renal replacement therapy in an intensive care unit. Introduction of extracorporeal membrane oxygenation was initiated to provide lung-protective ventilation supporting the recovery of his pulmonary function. Aminocaproic acid was used to stop and prevent further alveolar hemorrhage. He fully recovered thereafter; however, it is uncertain whether it was the use of aminocaproic acid that led to the resolution of his disease.

Background Concern for drug-drug interactions leading to treatment failure and drug-resistant strains have discouraged clinicians from attempting concomitant treatment of hepatitis C virus (HCV) and tuberculosis (TB). Increased metabolism of direct-acting antivirals (DAAs) by rifamycins has hindered concurrent use. Development of an assay for ledipasvir and sofosbuvir (LDV/SOF) serum concentrations for therapeutic drug monitoring (TDM) can ensure adequate therapy. We present the first cases of concomitant therapy of active TB and HCV with rifamycin-containing regimens and DAAs using TDM. Methods Using TDM, we aim to determine whether concomitant therapy with rifamycin-containing regimens and DAAs is safe and effective for patients coinfected with TB and HCV. Five individuals with TB and HCV who experienced transaminitis before or during TB therapy were concomitantly treated with rifamycin-containing regimens and LDV/SOF. Therapeutic drug monitoring was performed for LDV, SOF, and rifabutin during therapy. Baseline laboratory tests and serial liver enzymes were performed. Hepatitis C virus viral load and mycobacterial sputum cultures were obtained upon completion of therapy to determine efficacy of therapy. Results All patients were found to have nondetectable HCV viral loads and negative mycobacterial sputum cultures upon completion of therapy. No clinically significant adverse effects were reported. Conclusions These cases illustrate concomitant use of LDV/SOF and rifabutin in patients with HCV/TB coinfection. Utilizing serum drug concentration monitoring to guide dosing, correction of transaminitis were achieved, which allowed the use rifamycin-containing TB therapy. These findings suggest that concomitant therapy of TB/HCV is possible, safe, and effective. [ABSTRACT FROM AUTHOR]

Objetivo: Determinar los factores sociodemográficos asociados a la depresión en estudiantes de una secundaria pública del estado de Querétaro, México. Método: Investigación cuantitativa, alcance descriptivo-correlacional y corte transversal. Muestra conformada por 418 estudiantes. Recolección de información por medio de una cédula de datos sociodemográficos e Inventario de Depresión de Beck-IA (BDI-IA). Análisis por estadística descriptiva en el programa SPSS, en tanto que la estadística inferencial se realizó en el software R a través de Ji cuadrada de Pearson a partir de una tabla de contingencia para el nivel de depresión y cada factor sociodemográfico. Se proporcionó el consentimiento y asentimiento informado, respetando en todo momento la confidencialidad, libertad y voluntad en la participación de los adolescentes. Resultados principales: 57.7% mujeres, 49% estaban inscritos al primer año, 62.4% acudía a clase en el turno matutino, 91.9% se dedicaba sólo a estudiar y 58.1% practicaba deporte. 16% presenta leve perturbación del estado de ánimo, 5.3% depresión intermitente, 4.3% moderada, 1.9% grave y 1% depresión extrema. En la correlación sexo y nivel de depresión se obtuvo X2=33.833 (p=8.062e-07), grado escolar y nivel de depresión X2=21.288 (p=0.006421), práctica deportiva y nivel de depresión X2=13.195 (p=0.01036), turno y nivel de depresión X2=5.5836 (p=0.2325), ocupación y nivel de depresión X2=6.1243 (p=0.1901), nivel de depresión y con quien vive el adolescente X2=20.372 (p=0.06037). Conclusión general: Los factores sociodemográficos como sexo, grado escolar y práctica deportiva se asocian directamente a niveles de depresión en los adolescentes. El turno, la ocupación y con quien vive, son factores que no se relacionan con la presencia de depresión.

RESUMEN Introducción: La diabetes mellitus fue la segunda causa de mortalidad en México en 2015, algunas causas del problema son malos estilos de vida y desconocimiento de la enfermedad. Método: estudio observacional, transversal y descriptivo, n=106, evaluando estilos de vida, nivel de conocimientos y hemoglobina glicada. Resultados: el nivel de conocimiento así como el perfil promotor de salud es regular para ambos sexos. La HbA1c se relaciona con el perfil de salud r = .271, no así con el nivel de conocimiento. Los pacientes con DM2 presentan HbA1c = 8.96, los pacientes con DM2 y comorbilidades crónicas tienen HbA1c =7.55. Conclusiones: las intervenciones propuestas a la unidad de salud, deberán tener un enfoque en la promoción de estilos de vida saludables y no necesariamente en mejorar los conocimientos de la enfermedad.

Background: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring., Methods: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring., Results: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months., Conclusions: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible., Competing Interests: Potential conflicts of interest. C. A. H. reports honoraria from the Infectious Diseases Society of America for an IDWeek 2022 presentation, travel support from the University of Employer, and Pfizer stock ownership. M. C. S. reports grants from the National Institute of Minority Health and Health Disparities (R21MD017943-01; Neighborhood transportation vulnerability and geographic patterns of diabetes-related limb loss) and the American Diabetes Association (Diabetic Ulcer Computational Sensing System), paid to the institution, and payment from the Society for Advancement in Wound Care for speaking at the 2023 spring meeting. D. A. reports a grant from the Centers for Disease Control and Prevention (CDC) as the primary investigator of TB Centers of Excellence, travel support from the CDC, and participation in the CDC's Tuberculosis Trials Consortium data and safety monitoring board. L. C. reports grants from USAID (federal award to institution for global research capacity building) and the California Department of Public Health (training award to institution for pandemic response); an unpaid position as president of the Executive Leadership Board for the North American Region Union Against Tuberculosis and Lung Diseases; and an unpaid position on the coordinating board of STOP TB USA. M. B. D reports institutional contracts with the CDC and Westat. A. V. E. reports travel support for meetings from the CDC. K. A. R. reports grants and travel support from the CDC’s Division of TB Elimination and a position as the liaison for the National Association of County and City Health Officials to the Advisory Committee for the Elimination of Tuberculosis. M. C. R. reports travel support for meeting from Association of Public Health Laboratories (APHL) and positions as chair of the APHL Infectious Diseases Committee and member of the APHL Tuberculosis Subcommittee and the College of American Pathologists Microbiology Committee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)