Effects of antineoplastic and immunomodulating agents on postvaccination SARS-CoV-2 breakthrough infections, antibody response, and serological cytokine profile.

BACKGROUND: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging. METHODS: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization. RESULTS: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile. CONCLUSIONS: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets.

Improving Self-Confidence of Military Medical Providers With Joint Procedure Simulation: A Pilot Study.

INTRODUCTION: Military medical providers are a unique population that encounter different environments across the world. From hospital clinics to war zones, these providers must perform procedures and rely on their training and skill to help their patients. This pilot study aimed to assess the self-confidence of military medical providers performing joint aspiration and injection before and after a simulation workshop in both clinical and austere settings. METHODS: In 2016, 25 military physicians from various military facilities participated in a 1-hour knee arthrocentesis and injection and shoulder injection workshop. Education was provided on the knee and shoulder anatomy and various approaches to performing the procedures before the hands-on portion of the workshop. Surveys assessing self-reported confidence levels by performing the procedures in the clinic and austere settings were completed before and after simulation training. RESULTS: The results were analyzed and grouped based on the provider experience level, simulation environment, and specific procedure performed. There was a statistical significance seen in the shoulder arthrocentesis group, which included all participating providers, with a P-value of <.01 in the clinic setting and a P-value of <.001 in the austere setting. In the knee aspiration simulation, there were also improvements in the provider confidence, but it was not statistically significant with P-values of .36 and .14 in the clinical and austere settings, respectively. CONCLUSION: Simulation training can lead to increased medical provider self-confidence in performing musculoskeletal joint aspirations and injections in both clinic and austere settings. The military medicine demographics have had little research in joint injections and provider confidence to date. This pilot study was one of the first to evaluate this unique population. The methods used in this study, and the positive data collected on provider confidence, can be used in larger studies, encompassing other medical providers to increase the confidence of providers throughout various fields of medicine.

Measuring Mitochondrial Electron Transfer Complexes in Previously Frozen Cardiac Tissue from the Offspring of Sow: A Model to Assess Exercise-Induced Mitochondrial Bioenergetics Changes.

The mitochondrial electron transfer complex (ETC) profile is modified in the heart tissue of the offspring born to an exercised sow. The hypothesis proposed and tested was that a regular maternal exercise of a sow during pregnancy would increase the mitochondrial efficiency of offspring heart bioenergetics. This hypothesis was tested by isolating mitochondria using a mild-isolation procedure to assess mitochondrial ETC and supercomplex profiles. The procedure described here allowed for the processing of previously frozen archived heart tissues and eliminated the necessity of fresh mitochondria preparation for the assessment of mitochondrial ETC complexes, supercomplexes, and ETC complex activity profiles. This protocol describes the optimal ETC protein complex measurement in multiplexed antibody-based immunoblotting and super complex assessment using blue-native gel electrophoresis.

Protracted hyperthermia and delayed rhabdomyolysis in ecstasy toxicity: A case report.

RATIONALE: Despite toxicity and unpredictable adverse effects, ecstasy use has increased in the United States. Onset of hyperpyrexia, rhabdomyolysis, disseminated intravascular coagulation (DIC), among other symptoms, occurs within hours of ingestion. Moreover, patients who experience hyperpyrexia, altered mental status, DIC, and multiorgan failure, rarely survive. This case presents a chronic ecstasy user whose symptoms would have predicted mortality. The report demonstrates a patient who experiences protracted hyperthermia, with delayed rhabdomyolysis and DIC. In addition, his peak creatine kinase (CK) of 409,440 U/L was far greater than the expected 30,000 to 100,000 U/L, being the second largest CK recorded in a survivor. PATIENT CONCERNS: This case report presents a 20-year-old man who presented to the emergency department after experiencing a severe reaction to ecstasy. He was a chronic user who took his baseline dosage while performing at a music event. He experienced hyperpyrexia immediately (106.5°F) while becoming stiff and unresponsive. Before emergency medical service arrival, his friends placed cold compresses on the patient and rested him in an ice filled bathtub. DIAGNOSES: Per history from patient's friends and toxicology results, the patient was diagnosed with ecstasy overdose, which evolved to include protracted hyperthermia and delayed rhabdomyolysis. INTERVENTIONS: Due to a Glasgow coma scale score of 5, he was intubated and sedated with a propofol maintenance. Hyperpyrexia resolved (temperature dropped to 99.1°F) after start of propofol maintenance. He was extubated after 24 hours, upon which he experienced hyperthermia (101.4°F at 48 hours), delayed rhabdomyolysis, and DIC (onset at 37 hours). He remained in hyperthermia for 120 hours until carvedilol permanently returned his temperature to baseline. His plasma CK reached a peak of 409,440 U/L at 35 hours. OUTCOMES: After primary management with intravenous fluids, the patient returned to baseline health without any consequences and was discharged after 8 days. A follow-up of 3 months postdischarge revealed no complications or disability. LESSONS: Clinically, the case highlights how physicians should be aware of the unusual time course adverse effects of ecstasy can have. Lastly, as intensity and duration of hyperpyrexia are predictors of mortality, our case indicates maintenance of sedation with propofol and use of oral carvedilol; both are efficacious for temperature reduction in ecstasy toxicity.

Case Report on Fear of Falling Syndrome: A Debilitating but Curable Gait Disorder.

BACKGROUND Fear of falling syndrome is a rare and often-missed disorder among patients with new-onset gait abnormality. The disorder is often mistaken for an organic neurologic problem, with some considering it to be a medical emergency. CASE REPORT This case report presents a 70-year-old man who presented to the Emergency Department due to inability to rise from a chair or ambulate independently. Onset of his chief complaint occurred subsequent to a traumatic fall in a public location. He underwent extensive workup, and an organic neurologic cause was ruled out. He was subsequently diagnosed with fear of falling syndrome after obtaining a detailed fall history, as well as utilizing a verified survey (the Falls Efficacy Scale-International). After extensive inpatient treatment, the patient improved significantly. However, upon discharge to a skilled nursing facility, he was not offered the recommended treatment. When he was readmitted for an unrelated reason 3 months later, he had regressed to the state he was in at the time of prior admission. CONCLUSIONS This case presents a rare debilitating but reversible gait disorder, and highlights the importance of assessing "fall history" and fear of falling in older adults. Uniquely, this case presents the rapid fluctuation in outcomes dependent on treatment, and what happens when a patient fails to complete treatment regimens. The report also provides an overview of fear of falling with the corresponding gait disorder.