Hospitalization characteristics and outcomes of patients with cancer and COVID-19 at a comprehensive cancer center.

PURPOSE: Several studies have confirmed increased mortality among patients with both COVID-19 and cancer. It remains important to continue to report observations of morbidity and mortality from COVID-19 in this vulnerable population. The purpose of this study is to describe the hospitalization characteristics and outcomes of patients with both cancer and COVID-19 admitted to our comprehensive cancer center. METHODS: This was a descriptive study of the first COVID-19-related hospitalization among adult patients with cancer admitted to our institution. Descriptive statistics were used to summarize patient demographics, clinical as well as hospitalization characteristics. Overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: A total of 212 patients were included in our cohort with a mean age of 59 years. Fifty-four percent of patients had history of solid tumor malignancy and 46% had hematologic malignancies. Eighty-five percent of our cohort had active malignancy. The mean length of stay (LOS) for hospitalization was 11.2 days (median LOS of 6 days). Twenty-five percent had severe disease and 10.8% died during their initial hospitalization. Those who had severe disease had worse survival at the end of the observation period. CONCLUSIONS: COVID-19 among cancer patients causes significant morbidity and mortality as well as repeat hospitalizations. Continued study of COVID-19 in this vulnerable population is essential in order to better inform evolving treatment algorithms, public health policies, and infection control protocols, especially for institutions caring for patients with cancer.

The Terrible Triad of Checkpoint Inhibition: A Case Report of Myasthenia Gravis, Myocarditis, and Myositis Induced by Cemiplimab in a Patient with Metastatic Cutaneous Squamous Cell Carcinoma.

BACKGROUND: We report a case of a patient with squamous cell carcinoma (SCC) who developed myasthenia gravis (MG), myositis, and myocarditis after receiving cemiplimab, an anti-PD-1 immune checkpoint inhibitor (ICI). Case Presentation. An 86-year-old man with metastatic periocular SCC presented with decreased vision in the left eye, severe fatigue, and lower back and bilateral hip pain 3 weeks after receiving cemiplimab. Within hours, he developed dysphonia, pharyngeal secretions, and dysphagia, necessitating intubation. Endomyocardial biopsy revealed active lymphocyte-mediated necrosis consistent with ICI-induced myocarditis. Anti-striated muscle and anti-acetylcholine receptor antibodies were elevated, consistent with myositis and myasthenia gravis. Despite plasma exchange therapy, steroids, and intravenous immunoglobulin, he died from cardiac arrest. CONCLUSIONS: The presence of myasthenia gravis, myocarditis, or myositis should prompt evaluation for all three toxicities as they may represent an overlap syndrome. The severity of these immunotoxicities highlights the need for clinicians to suspect multiple simultaneous adverse effects of ICIs.

Role of Infliximab in Immune Checkpoint Inhibitor-Induced Pneumonitis.

Introduction: Since immune checkpoint inhibitor (ICI) blockade has become standard therapy for many cancers, immune-related adverse events (irAEs) have increased. ICI-pneumonitis is infrequent but potentially fatal. In cases not responsive to corticosteroids, additional immunosuppression is recommended. Data for use of infliximab in ≥ grade 3 pneumonitis is sparse. Materials and Methods: A retrospective review of patients who received infliximab for ICI-pneumonitis from March 2016 to October 2018 was performed. Clinical characteristics were reviewed. Results: Nine patients (44% women) with ≥ grade 3 pneumonitis were included. Concurrent/prior irAEs were present in 55%. Bronchoscopy was performed in 67%. Median corticosteroid dose was 1.2 mg/kg prior to infliximab, and time from administration of corticosteroids to infliximab ranged from 2 to 34 days. Four patients improved, but the remainder died. Conclusion: We report improvement of ICI-pneumonitis with infliximab in 4 out of 9 patients in a small, retrospective cohort. Further prospective randomized controlled trials are needed.

Impairments in timing, temporal memory, and reversal learning linked to neurotoxic regimens of methamphetamine intoxication.

Methamphetamine intoxication has long-term consequences on dopaminergic function and corticostriatal-mediated behaviors in humans and other animals. In order to determine the potential impact on timing and temporal memory, we examined methamphetamine dose regimens that have been linked to neurotoxicity in adult (8 months) male rats. Rats that were given repetitive, high-dose methamphetamine (3.0 mg/kg ip x 4 injections/2 h) or saline injections were trained on a 2-s vs 8-s bisection procedure using auditory and visual signal durations. Following the high-dose regimen, baseline timing performance was reestablished prior to the rats' receiving reversal training in which the spatial/temporal mapping of the anchor durations (2 s and 8 s) to response options (left or right lever) was reversed. Low-dose methamphetamine (0.5 mg/kg ip) or saline injections were subsequently used to evaluate the effectiveness of the neurotoxic doses in terms of modifying the horizontal leftward shifts associated with increases in clock speed. Overall, the results indicate that MAP intoxication leads to reduced auditory/visual differences in clock speed, deficits in reversal learning, distortions in temporal memory, and lowered dopaminergic regulation of clock speed consistent with damage to prefrontal cortex and corticostriatal circuitry.

Position of neocortical neurons transfected at different gestational ages with shRNA targeted against candidate dyslexia susceptibility genes.

Developmental dyslexia is a language learning disorder that affects approximately 4-10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including DCDC2 and KIAA0319 on Chromosome (Chr) 6p22.2 and DYX1C1 on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projection cell progenitors by in utero electroporation of plasmids encoding small hairpin RNA (shRNA) revealed that all three genes disrupted neuronal migration to the neocortex. Specifically, this disruption would result in heterotopia formation (Dyx1c1 and Kiaa0319) and/or overmigration past their expected laminar location (Dyx1c1 and Dcdc2). In these experiments, neurons normally destined for the upper neocortical laminæ were transfected on embryonic day (E) 15.5, and we designed experiments to test whether these migration phenotypes were the result of targeting a specific type of projection neuron. We transfected litters with Dcdc2 shRNA, Dyx1c1 shRNA, Kiaa0319 shRNA, or fluorescent protein (as a control) at each of three gestational ages (E14.5, E15.5, or E16.5). Pups were allowed to come to term, and their brains were examined at 3 weeks of age for the position of transfected cells. We found that age of transfection did not affect the percentage of unmigrated neurons--transfection with Kiaa0319 shRNA resulted in heterotopia formation at all three ages. Overmigration of neurons transfected with Dcdc2 shRNA, while present following transfections at the later ages, did not occur following E14.5 transfections. These results are considered in light of the known functions of each of these candidate dyslexia susceptibility genes.

"Speed" warps time: methamphetamine's interactive roles in drug abuse, habit formation, and the biological clocks of circadian and interval timing.

The indirect dopamine (DA) agonist methamphetamine (MAP) is evaluated in terms of its impact on the speed of temporal processing across multiple time scales involving both interval and circadian timing. Behavioral and neuropharmacological aspects of drug abuse, habit formation, neurotoxicity, and the potential links between interval and circadian timing are reviewed. The view that emerges is one in which the full spectrum of MAP-induced effects on timing and time perception is both complex and dynamic in as much as it involves DA-glutamate interactions and gene expression within cortico-striatal circuitry spanning oscillation periods ranging from milliseconds to multiple hours. The conclusion is that the psychostimulant properties of MAP are very much embedded within the context of temporal prediction and the anticipation of reward.