Valvular involvement in granulomatosis with polyangiitis: Case report and systematic review of literature.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a systemic inflammatory condition; however, patients with GPA rarely experience endocardial valve lesions. METHODS: We report a GPA case with tricuspid valve destruction together with a systematic review to highlight the characteristics of all previously reported GPA cases with valvular involvement. RESULTS: Among 36 cases included, the aortic valve was involved in 15 (41.7%) cases while the mitral valve was involved in 9 (25%) subjects. Combined lesion of both aortic and mitral valves was reported in 9 (25%) patients. CONCLUSION: We recommend routine echocardiography examination to rule out any cardiac valve lesion once GPA is suspected.

Post-Transplantation Cyclophosphamide and Ixazomib Combination Rescues Mice Subjected to Experimental Graft-versus-Host Disease and Is Superior to Either Agent Alone.

Lapses in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) warrant novel approaches. Such approaches include, among others, the use of post-transplantation cyclophosphamide (PTC) and proteasome inhibitors. Although PTC alone consistently produces low rates of chronic GVHD, the incidence of acute GVHD remains significant. Inversely, prolonged post-transplantation administration of proteasome inhibitors carries a risk of paradoxical aggravation of GVHD. We examined whether the combination of cyclophosphamide and ixazomib addresses the limitations of each of these agents when used alone to prevent GVHD in mice subjected to allogeneic HSCT across MHC barriers. We chose ixazomib, an orally bioavailable proteasome inhibitor, because of its favorable physiochemical characteristics. The combination of cyclophosphamide and ixazomib improved overall survival of mice in comparison to an untreated control group and to groups receiving either cyclophosphamide alone or ixazomib alone. Furthermore, cyclophosphamide prevented the surge of IL-1ß, GVHD aggravation, and sudden death associated with prolonged administration of ixazomib after HSCT. Finally, we demonstrated that although ixazomib was administered before cyclophosphamide, it did not impair the preferential depletion of proliferating as opposed to resting donor T cells. Our data suggest that the combination of cyclophosphamide and ixazomib for the prevention of GVHD after allogeneic HSCT is promising and merits further investigation in clinical trials.

Patient perspectives on topical minoxidil for hair loss: a survey-based study from the University of Michigan Alopecia Clinic.

Topical minoxidil is a widely used therapy for alopecia. Its availability over the counter in the United States makes it easily accessible. Various factors impact whether an individual decides to pursue treatment and/or continue long-term use. Our study aimed to investigate patient awareness, opinions, and hesitations regarding topical minoxidil use for hair loss treatment. The study also aimed to identify information sources influencing these viewpoints. A survey was administered to new patients seeking evaluation for alopecia aged 18 and above at the University of Michigan Alopecia Clinic. Data collection occurred between August 2022 and August 2023. Demographics, patient-reported hair loss diagnosis, history of minoxidil use, opinions on minoxidil, influential information sources, and concerns about minoxidil were collected. A total of 47 surveys were completed, primarily by females (78.7%) ages 18-40 years (44.7%). Respondents were aware of minoxidil (97.9%), with 63.8% reporting they had heard of minoxidil, but had not used it. Medical professionals were the most influential information source (34%), followed by close contacts (17%), internet searches (10.6%), and television (10.6%). Overall, positive opinions on minoxidil were expressed by 51.1%, negative opinions by 31.9%, and neutral opinions by 17%. Most common concerns included the need for continuous use (46.8%), required regular application (31.9%), skepticism about hair regrowth (29.8%), and expense (25.5%). Addressing personalized concerns and tailoring communication based on hair loss type and information sources may lead to more informed decisions and improved adherence. Gauging the opinions of this population provides valuable insights, aiding dermatologists in patient education and counseling strategies.

Deep Sedation in Pediatric Patients With Single Ventricle Physiology Outside of the Operating Room.

Background: Advancements in palliative surgery of patients with single ventricle physiology have led to an increase in the need for deep sedation protocols for painful procedures. However, positive pressure ventilation during anesthesia can result in unfavorable cardiopulmonary interactions. This patient population may benefit from sedation from these painful procedures. Methods: This study aims to demonstrate the safety and efficacy of deep sedation by pediatric intensivists outside the operating room for children with single ventricle physiology. This is a single-center, retrospective chart review on consecutive pediatric patients with single ventricle physiology who received deep sedation performed by pediatric intensivists between 2013 and 2020. Results: Thirty-three sedations were performed on 27 unique patients. The median age was 3.7 years (25th%-75th%: 2.1-15.6). The majority of the sedations, 88% (29/33), were done on children with Fontan physiology and 12% (4/33) were status-post superior cavopulmonary anastomosis. The primary cardiac defect was hypoplastic left heart in 63% (17/27) of all sedation procedures. There were 24 chest tube placements and 9 cardioversions. Ketamine alone [median dose 1.5 mg/kg (range 0.8-3.7)], ketamine [median dose 1 mg/kg (range 0.1-2.1)] with propofol [median dose 2.3 mg/kg (range 0.7-3.8)], and ketamine [median dose 1.5 mg/kg (range 0.4-3.0)] with morphine [median dose 0.06 mg/kg (range 0.03-0.20)] were the most common sedation regimens used. Adverse events (AEs) occurred in 4 patients (15%), three of which were transient AEs. All sedation encounters were successfully completed. Conclusion: Procedural deep sedation can be safely and effectively administered to single ventricle patients by intensivist-led sedation teams in selective case.

COVID-19 Associated With Encephalitis: Case Report and Review of Literature.

INTRODUCTION: Neurological problems may be part of severe and early course of coronavirus disease 2019 (COVID-19). COVID-19 associated encephalitis as an evident etiology of altered consciousness has been rarely reported in the literature. CASE REPORT: A case of 66-year-old female presented with classic COVID-19 symptoms and associated diabetic ketoacidosis. Although diabetic ketoacidosis was managed, the patient had persistent impaired level of consciousness with recurrent attacks of left focal fits because of COVID-19-associated encephalitis. However, the patient has markedly improved after recovering from COVID-19. CONCLUSION: Neurologists should be involved in the evaluation and management of COVID-19 patients who present with associated neurological problems.

Ixazomib suppresses human dendritic cell and modulates murine graft-versus-host disease in a schedule-dependent fashion.

There is an abiding need for innovative approaches to the prevention of graft-versus-host disease (GvHD) following allogeneic hematopoietic stem cell transplantation (HSCT). Interest in prevention of GvHD by dendritic cell (DC) suppression has re-emerged since the introduction of proteasome inhibitors into clinical practice. Ixazomib is an orally bioavailable proteasome inhibitor with a rapid proteasome dissociation rate. We studied the effects of ixazomib on human DC maturation, viability, and cytokine production in vitro. We also determined the effects of ixazomib in a murine GvHD model. Although ixazomib suppressed naïve human DC maturation, it had only a limited effect on cell viability. Ixazomib decreased pro-inflammatory cytokine production of resting DCs. This effect was diminished or reversed when DCs were pre-stimulated. In vivo, ixazomib administered post-transplantation on days +1 and +4 or days -1, +2, and +5 ameliorated GvHD in comparison to the GvHD group. Although a fraction of mice treated according to the prolonged schedule died abruptly after the day +5 treatment, both schedules resulted in improved overall survival. When we examined the effects of ixazomib on splenic cells and serum cytokines, we found that ixazomib exerted complex schedule-dependent immunomodulatory effects. Our study provides a rationale for the potential use of ixazomib in the prevention of GvHD.