Faculty Bibliography

Digital spatial profiling (DSP) facilitates RNA sequencing (RNA-seq) of small populations of cells, specifically ~20 pyramidal neurons in postmortem formalin-fixed paraffin-embedded (FFPE) human brain tissue. This approach enables precise expression profiling via RNA-seq data linked to spatially characterized samples utilizing tissue-bound probes. We present a comprehensive protocol for manual slide preparation using the GeoMx DSP system as preliminary steps to spatial characterization of lamina-specific pyramidal neurons in human postmortem Brodmann area 9 (BA9) frontal cortex brain tissue.

BACKGROUND:Oral pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) provision via online pharmacies (henceforth online PrEP and PEP) offers promise in increasing biomedical HIV prevention coverage. In this study, we aimed to estimate the cost-effectiveness of online PrEP and PEP scale-up in western Kenya. METHODS:We adapted a network-based model, EMOD-HIV, to simulate online PrEP and PEP implementation from 2026 to 2036; costs and use of online PrEP and PEP and client characteristics were informed by the ePrEP Kenya pilot study, which evaluated online PrEP and PEP provision in Nairobi and Mombasa, Kenya. Other parameters were obtained from surveillance data and published literature. Eligible clients were aged 15-49 years reporting condomless sex with non-marital partners. We assumed online PrEP and PEP provision was implemented through public-private partnership, with the Kenya Ministry of Health providing PrEP and PEP drugs and service delivery costs paid by the online pharmacy (and charged to clients). We estimated HIV infections, HIV-related deaths, and disability-adjusted life-years (DALYs) averted compared with the baseline scenario of background oral PrEP only. We calculated incremental cost-effectiveness ratios (ICERs) assessing only costs incurred by the Kenya Ministry of Health over 35 years and used a supply-side threshold of US$500 per DALY averted. We calculated 95% uncertainty intervals (UIs) across 100 parameter sets. FINDINGS/RESULTS:Online PrEP and PEP was projected to reach population coverage of 0·7% (95% UI 0·7-0·8) for PEP and 0·3% (0·2-0·3) for PrEP and avert 13·9% (10·1-17·1) of HIV infections over 10 years. HIV-related deaths were reduced by 4·3% (95% UI 2·0-6·9) over the 35-year time horizon. The intervention was cost-effective from the Kenya Ministry of Health perspective (ICER $212 [95% UI 15-1409] per DALY averted). In a scenario assuming only online PEP availability (to isolate the effect of PEP), 11·6% (95% UI 8·6-15·2) of HIV infections were averted (ICER $210 [95% UI 41-3798] per DALY averted). The intervention remained cost-effective when varying PrEP and PEP effectiveness and assuming HIV testing and treatment disruptions. INTERPRETATION/CONCLUSIONS:Online PrEP and PEP can avert substantial HIV infections, even with low population coverage. PEP was responsible for most intervention health benefits, likely due to high observed demand for PEP compared with PrEP in the pilot study. Leveraging private retailers can be efficient for scaling up HIV prevention in an era of shrinking donor funding. FUNDING/BACKGROUND:Gates Foundation.

BACKGROUND:The purpose of this study was to compare outcomes of distal radius fractures with a volar ulnar corner (VUC) component treated with standard volar plating or by specific VUC fixation. This study investigated outcomes, radiographic measures, and specialty-based preference associated with surgical treatment of VUC injuries using VUC-specific fixation versus nonspecific VUC fixation. METHODS:We retrospectively analyzed outcomes for 39 patients with a distal radius fracture with VUC component at a level-1 trauma center over 10 years, 2011-2021. Patients underwent either VUC-specific fixation with implants such as a volar rim plate, or with a standard volar plate. The primary outcome of this study was fixation failure and need for revision. Secondary outcomes included complication rate, radiographic alignment, and differences in fixation based on fellowship training. RESULTS:Sixteen of the 39 patients studied had undergone VUC-specific fixation, with a significantly higher rate of use of VUC-specific fixation in fellowship trained hand surgeons compared with fellowship-trained trauma surgeons. There was no significant difference in loss of reduction, revision surgery, or complications. Radiographic measures were statistically similar between both groups postoperatively. Trauma trained surgeons had a significantly increased postoperative radial inclination versus hand-trained surgeons. CONCLUSIONS:This study suggests that not all VUC injuries require specific VUC fixation, and we may be overtreating distal radius fractures that have a VUC component. Fellowship-trained hand surgeons are more likely to employ VUC-specific fixation methods. Additional studies are warranted to determine whether other considerations such as dynamic testing intraoperatively are worthwhile.

BACKGROUND:Sinus of Valsalva aneurysms (SVAs) are rare cardiac anomalies that often remain silent until rupture occurs. Prompt recognition and repair is essential, as untreated ruptured SVAs can lead to progressive right heart failure and early mortality. CASE SUMMARY:A 26-year-old woman with a ruptured SVA and aorto-right atrial fistula underwent definitive surgical repair after failed transcatheter closure, with excellent postoperative recovery. DISCUSSION:Ruptured SVAs are rare and can present with subtle symptoms that can mimic other pathologies. Astute clinical examination, multimodal imaging, and timely surgical management all assist in ensuring excellent long-term outcomes. TAKE-HOME MESSAGE:Early recognition and meticulous perioperative management of ruptured SVAs are the keys to ensuring excellent long-term outcomes.