An Orbital Manifestation of VEXAS Syndrome.

VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis, arthritis, chondritis, dermatosis) and hematologic abnormalities (thrombosis, cytopenia, vacuolization of marrow precursors). The patient demonstrated some of the adult-onset inflammatory and hematologic features, in addition to recurrent eye pain, chemosis and orbital inflammation. This case describes an instance of VEXAS syndrome in a patient with uncommon orbital symptoms such as scleritis and myositis.

Trends in Neurotrauma Epidemiology, Management, and Outcomes during the COVID-19 Pandemic in Kigali, Rwanda.

National regulations to curb the coronavirus disease 2019 (COVID-19) transmission and health care resource reallocation may have impacted incidence and treatment for neurotrauma, including traumatic brain injury (TBI) and spinal trauma, but these trends have not been characterized in Sub-Saharan Africa. This study analyzes differences in epidemiology, management, and outcomes preceding and during the COVID-19 pandemic for neurotrauma patients in a Rwandan tertiary hospital. The study setting was the Centre Hospitalier Universitaire de Kigali (CHUK), Rwanda's national referral hospital. Adult injury patients presenting to the CHUK Emergency Department (ED) were prospectively enrolled from January 27, 2020 to June 28, 2020. Study personnel collected data on demographics, injury characteristics, serial neurological examinations, treatment, and outcomes. Differences in patients before (January 27, 2020 to March 21, 2020) and during (June 1, 2020 to June 28, 2020) the COVID-19 pandemic were assessed using chi-squared and Mann-Whitney U tests. The study population included 216 patients with neurotrauma (83.8% TBI, 8.3% spine trauma, and 7.9% with both). Mean age was 34.1 years (standard deviation [SD] = 12.5) and 77.8% were male. Patients predominantly experienced injury following a road traffic accident (RTA; 65.7%). Weekly volume for TBI (mean = 16.5 vs. 17.1, p = 0.819) and spine trauma (mean = 2.0 vs. 3.4, p = 0.086) was similar between study periods. During the pandemic, patients had lower Glasgow Coma Scale (GCS) scores (mean = 13.8 vs. 14.3, p = 0.068) and Kampala Trauma Scores (KTS; mean = 14.0 vs. 14.3, p = 0.097) on arrival, denoting higher injury severity, but these differences only approached significance. Patients treated during the pandemic period had higher occurrence of hemorrhage, contusion, or fracture on computed tomography (CT) imaging (47.1% vs. 26.7%, p = 0.003) and neurological decline (18.6% vs. 7.5%, p = 0.016). Hospitalizations also increased significantly during COVID-19 (54.6% vs. 39.9%, p = 0.048). Craniotomy rates doubled during the pandemic period (25.7% vs. 13.7%, p = 0.003), but mortality was unchanged (5.5% vs. 5.7%, p = 0.944). Neurotrauma volume remained unchanged at CHUK during the COVID-19 pandemic, but presenting patients had higher injury acuity and craniotomy rates. These findings may inform care during pandemic conditions in Rwanda and similar settings.

Underrepresentation in Pelvic Floor Disorder Patient-Reported Outcomes: Whose Outcomes Are We Measuring?

IMPORTANCE: Patient-reported outcome (PRO) instruments measure the patient's perspective. It is unclear whether commonly used PRO measures were tested in populations that had racial and ethnic distributions comparable with those reported in U.S. census data. OBJECTIVE: The aim of this study was to compare the proportion of non-White race and Hispanic ethnicity participants with their expected proportion based on U.S. census data for PRO instruments with U.S.-based validation studies. STUDY DESIGN: This was a retrospective review of PRO measures considered by the Pelvic Floors Disorders Consortium Working Group on Patient-Reported Outcomes in their 2020 consensus publication. Study and participant information were abstracted from PRO validation studies. Racial and ethnic representation in U.S.-based studies were compared with U.S. census data. The primary outcome was the representation quotient of reported races and ethnicities, calculated as the reported percentage of the study population identifying with a race and/or ethnicity divided by the proportion of the U.S. population identifying with that race and/or ethnicity when the study was published. RESULTS: Forty-five studies with 21,080 total participants were included. Race was reported in 17 of 45 studies (37.8%), and ethnicity was reported in 7 of 45 (15.6%). Most studies did not specify how race and ethnicity information was collected. For U.S.-based studies, the representation quotient of White participants from 1995 to 2019 was 1.15. Indigenous American/Native American/American Indian/Alaska Natives had the lowest representation quotient (0.22). Reporting of ethnicity increased over time (P = 0.001), although there was no significant change in the reporting of race or the representation of various races and ethnicities (P > 0.05). CONCLUSION: Non-White and Hispanic patients may be underrepresented in U.S.-based validation studies for PRO instruments in pelvic floor disorders.

Factors associated with HIV testing among patients seeking emergent injury care in Kigali, Rwanda.

Introduction: Emergency centres (ECs) can be important access points for HIV testing. In Rwanda, one in eight people with HIV are unaware of their infection status, which impedes epidemic control. This could be addressed via increased testing. This cross-sectional study evaluated factors associated with EC-based HIV testing among injured patients at the Centre Hospitalier Universitaire de Kigali (CHUK), in Kigali, Rwanda. Methods: Adult injury patients were prospectively enrolled between January-June 2020. Trained study personnel collected data on demographics, injury aspects, treatments, HIV testing, and disposition. The primary outcome was the completion of EC-based HIV testing. Differences between those receiving and those not receiving testing were assessed. Regression models yielding adjusted odds ratios with associated 95% confidence intervals (CI) were calculated to quantify magnitudes of effect. Results: Among 579 patients, the majority were under 45 years of age (78.1%) and male (74.4%). The most common mechanism of injury was road traffic accidents (50.3%). EC discharge occurred in 54.4% of cases. HIV testing was performed in 221 (38.2%) cases, of which 5.9% had a positive result. HIV testing was more likely among males (aOR=1.69, 95% CI: 1.02-2.78; p=0.04), cases transported by prehospital services (aOR=2.07, 95% CI: 1.28-3.35; p=0.003) and those receiving surgical consultation (aOR=3.13, 95% CI: 1.99-4.94; p<0.001). Cases with lower acuity were less likely to be tested (OR=0.70, 95% CI: 0.55-0.90; p=0.004), as were those discharged (OR=0.28, 95% CI: 0.18-0.43; p<0.001). Conclusion: In the population studied, most patients did not undergo HIV testing. EC-based physician directed testing was more likely among male patients and patients with greater care needs. These results may inform approaches to increase EC-based testing services in Rwanda and other similar settings with high HIV burdens.

PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.

The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase are clonal driver events in 11% of Diffuse Midline Gliomas (DMGs) and are enriched in primary pontine tumors. Through the development of DMG mouse models, we show that PPM1D mutations potentiate gliomagenesis and that PPM1D phosphatase activity is required for in vivo oncogenesis. Finally, we apply integrative phosphoproteomic and functional genomics assays and find that oncogenic effects of PPM1D truncation converge on regulators of cell cycle, DNA damage response, and p53 pathways, revealing therapeutic vulnerabilities including MDM2 inhibition.

Injury burdens and care delivery in relation to the COVID-19 pandemic in Kigali, Rwanda: A prospective interrupted cross-sectional study.

INTRODUCTION: Injuries cause significant burdens in sub-Saharan Africa. In Rwanda, national regulations to reduce COVID-19 altered population mobility and resource allocations. This study evaluated epidemiological trends and care among injured patients preceding and during the COVID-19 pandemic at the Centre Hospitalier Universitaire de Kigali (CHUK) in Kigali, Rwanda. METHODS: This prospective interrupted cross-sectional study enrolled injured adult patients (≥15 years) presenting to the CHUK emergency department (ED) from January 27th-March 21st (pre-COVID-19 period) and June 1st-28th (intra-COVID-19 period). Trained study personnel continuously collected standardized data on enrolled participants through the first six-hours of ED care. The Kampala Trauma Score (KTS) was calculated as a metric of injury severity. Case characteristics prior to and during the pandemic were compared, statistical differences were assessed using χ2 or Fisher's exact tests. RESULTS: Data were collected from 409 pre-COVID-19 and 194 intra-COVID-19 cases. Median age was 32, with a male predominance (74.3%). Road traffic injuries (RTI) were the most common injury mechanism pre-COVID-19 (47.8%) and intra-COVID-19 (53.6%) (p = 0.27). There was a significant increase in the number of transfer cases during the intra-COVID-19 period (52.1%) versus pre-COVID-19 (41.3%) (p = 0.01). KTS was significantly lower among intra-COVID-19 patients (p = 0.04), indicating higher severity of presentation. In the intra-COVID-19 period, there was a significant increase in the number of surgery consultations (40.7%) versus pre-COVID-19 (26.7%) (p < 0.001). The number of hospital admissions increased from 35.5% pre-COVID-19 to 46.4% intra-COVID-19 (p = 0.01). There was no significant mortality difference pre-COVID-19 as compared to the intra-COVID-19 period among injured patients (p = 0.76). CONCLUSION: Emergency injury care showed increased injury burden, inpatient admission and resource requirements during the pandemic period. This suggests the spectrum of disease may be more severe and that greater resources for injury management may continue to be needed during the ongoing COVID-19 pandemic in Rwanda and other similar settings.