Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness - A case series.

BACKGROUND: There is still a lot unknown about the novel Coronavirus Disease 19 (COVID-19) and its effects in humans. This pandemic has posed several challenging clinical situations to healthcare providers. OBJECTIVE: We hope to highlight the distinctive challenges that COVID-19 presents in patients with serious mental illness and what steps primary medical teams can take to co-manage these patients with the psychiatry consultants. METHODS: We present a retrospective chart review of four patients who were on psychotropic polypharmacy and admitted to our hospital from the same long-term psychiatric facility with COVID-19 delirium and other associated medical complications. RESULTS: We illustrate how the primary medical teams and psychiatrists collaborated in clinical diagnosis, treatment, and management. CONCLUSIONS: Patients with serious mental illness and COVID-19 infection require active collaboration between primary medical teams and psychiatrists for diagnostic clarification, reduction of psychotropic polypharmacy to avoid adverse effects and drug-drug interactions, prevention of psychiatric decompensation, and active management of agitation while balancing staff and patient safety concerns.

B lymphocyte-induced maturation protein-1 contributes to intestinal mucosa homeostasis by limiting the number of IL-17-producing CD4+ T cells.

The transcription factor B lymphocyte-induced maturation protein-1 (Blimp-1) plays important roles in embryonic development and immunity. Blimp-1 is required for the differentiation of plasma cells, and mice with T cell-specific deletion of Blimp-1 (Blimp-1CKO mice) develop a fatal inflammatory response in the colon. Previous work demonstrated that lack of Blimp-1 in CD4(+) and CD8(+) T cells leads to intrinsic functional defects, but little is known about the functional role of Blimp-1 in regulating differentiation of Th cells in vivo and their contribution to the chronic intestinal inflammation observed in the Blimp1CKO mice. In this study, we show that Blimp-1 is required to restrain the production of the inflammatory cytokine IL-17 by Th cells in vivo. Blimp-1CKO mice have greater numbers of IL-17-producing TCRß(+)CD4(+)cells in lymphoid organs and in the intestinal mucosa. The increase in IL-17-producing cells was not restored to normal levels in wild-type and Blimp-1CKO-mixed bone marrow chimeric mice, suggesting an intrinsic role for Blimp-1 in constraining the production of IL-17 in vivo. The observation that Blimp-1-deficient CD4(+) T cells are more prone to differentiate into IL-17(+)/IFN-γ(+) cells and cause severe colitis when transferred to Rag1-deficient mice provides further evidence that Blimp-1 represses IL-17 production. Analysis of Blimp-1 expression at the single cell level during Th differentiation reveals that Blimp-1 expression is induced in Th1 and Th2 but repressed by TGF-ß in Th17 cells. Collectively, the results described here establish a new role for Blimp-1 in regulating IL-17 production in vivo.

Regulatory and Service System Challenges in Accessing Electroconvulsive Therapy for Catatonia in the Presence of Autism Spectrum Disorder.

In a recent letter to the editor, Dr. Miller and colleagues1 highlighted the disparity of electroconvulsive therapy (ECT) across different states, and the challenges faced by a patient in Colorado for whom ECT was deemed the most appropriate treatment but was not available in this location, forcing the patient to seek care in New Mexico. A subsequent letter by Dr. Ong and colleagues2 presented an additional case, in a different location, where a delay in ECT treatment because of state regulations contributed to substantial patient morbidity. In this letter, we present a patient seen at our facility in California, a state with some of the most stringent regulations regarding ECT treatment in adolescents.3 This case illustrates how ECT was eventually approved by the court system only after the patient's continual deterioration, despite receiving intensive medical treatment on an inpatient pediatric medical unit for a duration of 80 days. Care providers and the patient's family were forced to witness this decline until the patient reached "an emergency situation" and ECT was "deemed a lifesaving treatment," as the California Welfare and Institutions Code (WIC) § 5,326.8(a) forbids the procedure under any other circumstances.

A Rise in Aspartate Transaminase and Alanine Transaminase Associated With Ondansetron Administration in a Pregnant Female.

Ondansetron (ODSN) is a commonly used and well-tolerated anti-emetic used during pregnancy. Upon review, three cases were identified in which liver function tests (LFTs) were elevated after ODSN administration without concurrent chemotherapy. In this report, we present a case of a 28-year-old pregnant female experiencing psychosis who developed serum level elevation of aspartate transaminase (AST) and alanine transaminase (ALT). An extensive workup left drug-induced liver injury as the most likely etiology. On retrospective review, we were able to demonstrate a clear relationship between ODSN administration and the rise of ALT and AST serum levels. A 28-year-old female gravida 3 para 2, who was 28 weeks pregnant, presented to a county hospital with new-onset psychotic features and persistent vomiting. She was diagnosed with major depressive disorder (MDD) with psychotic features and hyperemesis gravidarum (HG). She was started on medications to treat both conditions including as needed ODSN. Several days after admission, her serum levels of AST and ALT began to rise, eventually plateauing at an AST value of 267 units/liter (U/L) and an ALT value of 605 U/L on hospital day 10 and subsequently started decreasing. A comprehensive workup was performed to identify the cause of her hypertransaminasemia. Multiple causes were ruled out, with the most likely etiology determined to be drug-induced liver injury. She was admitted to the psychiatric emergency room (PER) on two separate occasions due to psychotic decompensation from medication noncompliance. On both occasions, her AST and ALT values were within normal limits. Ten weeks from the first admission she came for delivery. The patient had been medication compliant prior to delivery and displayed no features of psychosis. Notably, her AST and ALT were elevated and continued to rise until her delivery after which the serum levels decreased. A sharp rise in the plasma concentration of ALT and AST indicates an acute injury liver. As noted in the case presentation, medical workup ruled out many possible etiologies of her hypertransaminasemia. An important differential to consider was HG, however, based on the history and timing of LFT rise, this differential was unlikely. With other differential diagnoses ruled out, medication-induced hepatotoxicity was the most likely diagnosis. Next, by reviewing the medication administration record we found a temporal relationship between the onset and discontinuation of ODSN and the pattern of AST and ALT levels. Temporal relationships between AST and ALT levels were able to be excluded from all other medications this patient received. With limited reports indicating the hepatotoxicity potential of ODSN in the absence of concomitant chemotherapy administration, we hope this report adds to the literature and potentially assists future clinical decision making.

Peduncular hallucinosis associated with a pontine cavernoma.

Peduncluar hallucinosis is a rare neurological disorder characterized by visual hallucinations, often described to be vivid and dream-like. While the exact pathophysiology has yet to be elucidated, most cases to date have suggested an etiology stemming from lesions to the thalamus or midbrain. Here presented is a case of a 54-year-old female with peduncular hallucinosis secondary to a pontine cavernoma hemorrhage in the setting of essential hypertension. The patient's vivid visual and auditory hallucinations aligned temporally with the lesion's discovery and resolved after pharmaceutical treatment. This case represents a rare form of peduncular hallucinosis secondary to a pontine cavernoma hemorrhage leading to vasospasm in the arteries feeding the brain-stem.

Blimp-1 Functions as a Molecular Switch to Prevent Inflammatory Activity in Foxp3+RORγt+ Regulatory T Cells.

Foxp3+ regulatory T cells (Treg) are essential modulators of immune responses, but the molecular mechanisms underlying their function are not fully understood. Here we show that the transcription factor Blimp-1 is a crucial regulator of the Foxp3+RORγt+ Treg subset. The intrinsic expression of Blimp-1 in these cells is required to prevent production of Th17-associated cytokines. Direct binding of Blimp-1 to the Il17 locus in Treg is associated with inhibitory histone modifications but unaltered binding of RORγt. In the absence of Blimp-1, the Il17 locus is activated, with increased occupancy of the co-activator p300 and abundant binding of the transcriptional regulator IRF4, which is required, along with RORγt, for IL-17 expression in the absence of Blimp-1. We also show that despite their sustained expression of Foxp3, Blimp-1-/- RORγt+IL-17-producing Treg lose suppressor function and can promote intestinal inflammation, indicating that repression of Th17-associated cytokines by Blimp-1 is a crucial requirement for RORγt+ Treg function.

Differential regulation of Effector and Regulatory T cell function by Blimp1.

The transcriptional regulator Blimp1 plays crucial roles in controlling terminal differentiation in several lineages. In T cells, Blimp1 is expressed in both effector (Teff) and regulatory (Treg) cells, and mice with T cell-specific deletion of Blimp1 (Blimp1CKO mice) spontaneously develop severe intestinal inflammation, indicating a crucial role for Blimp1 in T cell homeostasis regulation. Blimp1 has been shown to function as a direct activator of the Il10 gene and although its requirement for IL10 expression has been demonstrated in both Treg and Teff cells under inflammatory conditions, the intrinsic requirement of Blimp1 for homeostatic maintenance of these T cell subsets had not been investigated. Using mice with Foxp3+ Treg-cell specific deletion of Blimp1 and other approaches, here we show that Foxp3+ Treg cell-intrinsic expression of Blimp1 is required to control Treg and Teff cells homeostasis but, unexpectedly, it is dispensable to prevent development of severe spontaneous intestinal inflammation. In addition, we show that Blimp1 controls common and unique aspects of Treg and Teff cell function by differentially regulating gene expression in these T cell subsets. These findings document previously unappreciated aspects of Blimp1's role in T cell biology and shed light on the intricate mechanisms regulating Treg and Teff cell function.