Faculty Bibliography

BackgroundThe exact incidence of cyst formation after graft transplantation for osteochondral lesions is unknown. The primary purpose was to assess and compare cystic occurrence after autografting, allografting, and osteoperiosteal grafting for osteochondral lesions of the talus. Our secondary aim was to assess the correlation of clinical outcomes with the presence of postoperative cysts.MethodsA literature search was performed up to October 2023 through PubMed, Embase (Ovid), and Cochrane Library. The primary outcome was the postoperative cystic occurrence rate. A random-effects model with moderator analysis was used to calculate differences in occurrence rates between treatment groups. The relationship between the presence of cysts and clinical outcomes was described.ResultsThirteen studies were included with 382 ankles. The average radiological follow-up at which the presence of cystic occurrence was assessed ranged from 12 to 84 months. The rates of cystic occurrence for the osteochondral autograft transplantation group, the allograft transplantation group, and the osteoperiosteal transplantation group were 42% (95% confidence interval [CI] = 24-61), 58% (95% CI = 40-74), and 34% (95% CI = 12-67), respectively, without any significant differences noted. No relationship between the presence of cysts and clinical outcomes was found.ConclusionPostoperative cystic occurrence is common after osteochondral autograft transplantation (42%), allograft transplantation (58%), and osteoperiosteal transplantation (34%) in osteochondral lesions of the talus-without significant intertreatment differences. The postoperative presence of cysts was not correlated with clinical outcomes. Future research should assess whether the postoperative presence of cysts correlates with (clinical) outcomes at longer follow-up.Level of Evidence:Level IV, systematic review and meta-analysis.

BACKGROUND/UNASSIGNED:Previous research has primarily examined individual factors of cardiovascular health (CVH) and disease in PD and dementia, but no study has examined CVH measures with PD, dementia, and mortality simultaneously while accounting for potentially confounding factors. OBJECTIVES/UNASSIGNED:To examine the relationship between CVH, all-cause dementia, Parkinson's disease (PD), and mortality, focusing on associations and health transitions from a large population-based study. METHODS/UNASSIGNED:We investigated these relationships using Cox Proportional Hazards and multistate parametric models with Weibull regression from the UK Biobank data (n = 269,816, Age = 50 + y individuals, ≤15y follow-up, 2006-2021). RESULTS/UNASSIGNED:), to be associated with increased risks for all-cause dementia (Hazard Ratio (HR) = 1.14, 95 % CI: 1.11-1.18, P < 0.001) and all-cause mortality (HR = 1.31, 95 % CI: 1.29-1.33, P < 0.001). Unlike "Healthy to PD" and "Dementia→Death" transitions, PD→Death (Weibull full model: HR = 1.18, 95 % CI: 1.06-1.31, P = 0.002), Healthy→dementia (HR = 1.15, 95 % CI: 1.12-1.19, P < 0.001), and Healthy→Death (HR = 1.33, 95 % CI: 1.32-1.35, P < 0.001) exhibited a positive relationship with poor CVH. CONCLUSIONS/UNASSIGNED:Poor CVH is directly associated with an increased risk of mortality from PD, transition into Dementia, and all-cause mortality without dementia or PD occurrence. Clinicians should aggressively screen for and manage CVH risk measures to reduce the risk of poor cognitive health outcomes.

Soft tissue sarcomas (STSs) are a diverse group of malignant tumors derived from mesenchymal tissues [...].

Leigh syndrome is a progressive infantile neurodegenerative disorder of mitochondrial metabolism that often leads to decompensation in the setting of metabolic stress. It is genetically heterogenous with varied inheritance patterns. One subtype includes NDUFS8-related autosomal recessive Leigh syndrome. This nuclear gene encodes a complex I subunit of the mitochondrial complex chain. Although Leigh syndrome is typically associated with basal ganglia and brainstem involvement, cases of confluent white matter disease have been described with NDUFS8-related disorders. We present the case of a 6-month-old girl with initial imaging suggestive of a leukodystrophy, later found to have a novel homozygous variant in NDUFS8. In conjunction with the clinical course, a diagnosis of Leigh syndrome was made. This case highlights that mitochondrial disorders should be considered on the differential for confluent cerebral white matter disease in early childhood.

BACKGROUND:Innovation in gastroenterology (GI) is experiencing several favorable tailwinds. Despite the increasing amount of capital invested in the technology and pharmaceutical sectors of GI, trends in venture capital (VC) funding for this field remain understudied. This is the first analysis of VC investment in GI. PURPOSE/OBJECTIVE:This study aimed to understand the allocation of VC investment in gastroenterology from 2012 to 2022. METHODS:We conducted a retrospective cross-sectional analysis of VC investments in gastroenterology from January 1, 2012, to December 31, 2022. Data was obtained from the PitchBook private capital market database. Investments were categorized broadly into biotechnology, pharmaceuticals, devices and supplies, healthcare services, etc. Total and annual investments were quantified in USD. RESULTS:From 2012 to 2022, $33.34 billion was invested in gastroenterology fields involving 3419 deals with steadily increasing growth, representing a compound annual growth rate of 15.7% between 2012 and 2022. Pharmaceuticals and biotechnology received the largest share (64.61%) followed by healthcare devices and supplies (12.75%). Investments in pharmaceuticals and technology had an outstanding increase from 2019 to 2020 of 141% and has yielded the largest sector in each year throughout 2012 and 2022. CONCLUSION/CONCLUSIONS:Our study highlights a notable rise in both the value and volume of VC investments in gastroenterology over time. Particularly noteworthy is the escalating allocation of funds toward biotechnology, pharmaceuticals, and devices which have skyrocketed over the past few years, suggesting a long-term financial interest in the success of gastroenterology innovation. Further research will be needed to explore the impact of VC funding in the field of gastroenterology.

Short-range association fibers located in the superficial white matter play an important role in mediating higher-order cognitive function in humans. Detailed morphological characterization of short-range association fibers at the microscopic level promises to yield important insights into the axonal features driving cortico-cortical connectivity in the human brain yet has been difficult to achieve to date due to the challenges of imaging at nanometer-scale resolution over large tissue volumes. This work presents results from multi-beam scanning electron microscopy (EM) data acquired at 4 × 4 × 33 nm³ resolution in a volume of human superficial white matter measuring 200 × 200 × 112 μm (Braitenberg and Schüz, 2013), leveraging automated analysis methods. Myelin and myelinated axons were automatically segmented using deep convolutional neural networks (CNNs), assisted by transfer learning and dropout regularization techniques. A total of 128,285 myelinated axons were segmented, of which 70,321 and 2,102 were longer than 10 and 100 μm, respectively. Marked local variations in diameter (i.e., beading) and direction (i.e., undulation) were observed along the length of individual axons. Myelinated axons longer than 10 μm had inner diameters around 0.5 µm, outer diameters around 1 µm, and g-ratios around 0.5. This work fills a gap in knowledge of axonal morphometry in the superficial white matter and provides a large 3D human EM dataset and accurate segmentation results for a variety of future studies in different fields.

Traditionally, acetabular global overcoverage had been treated by open surgical dislocation of the hip and was a relative contraindication for hip arthroscopy. With advancing arthroscopic techniques, hip arthroscopy can successfully treat acetabular global overcoverage with less morbidity for the patient than an open hip procedure. Successful arthroscopic treatment of this condition is not for the beginner hip arthroscopist. Pitfalls of an arthroscopic technique include difficult entry into the joint and labral insufficiency with the inability to perform a repair and these difficulties should be understood ahead of the procedure. However, with careful, thoughtful technique, arthroscopic treatment of acetabular global overcoverage has successful outcomes and now should be considered the preferred option instead of open surgical dislocation of the hip.

Rituximab (RTX) is a monoclonal anti-CD20 antibody widely used to treat B-cell neoplasms and autoimmune conditions. RTX has recently been linked to an enteropathy characterized by diarrhea, malabsorption, and hypogammaglobulinemia, closely resembling common variable immunodeficiency (CVID) enteropathy. We present the first dedicated histopathologic assessment of RTX-associated CVID-like enteropathy. Study inclusion criteria were the presence of diarrhea, weight loss, or other gastrointestinal (GI) symptoms in the setting of current/prior RTX use and associated hypogammaglobulinemia. Twenty-two patients (15M:7F; mean age at biopsy/resection, 63.4y) across 9 tertiary medical centers met inclusion criteria and had small bowel (N=20) and/or colon (N=17) specimens (biopsies/resections) available for review; 71.4% of specimens dated from ≤5y of last RTX dose. Cases were systematically evaluated by GI pathologists at each institution. Key histologic features in the small bowel included sparse/absent lamina propria plasma cells (N=10, 50%), intraepithelial lymphocytosis (N=12, 60%), villous atrophy (N=11, 55%), increased crypt apoptotic bodies (N=6, 30%), and active inflammation (N=5, 25%). Common features in the colon included sparse/absent plasma cells (N=7, 41.2%), increased crypt apoptotic bodies (N=7, 41.2%), active inflammation (N=5, 29.4%), and intraepithelial lymphocytosis (N=4, 23.5%). Goblet cell loss was appreciated in small bowel and/or colon specimens from 2 patients. Follow-up biopsies (interval, 2m-4y) were available for 7 patients and largely recapitulated the histology of the index specimens, though 1 patient demonstrated improvement in villous blunting and intraepithelial lymphocytosis. In summary, the histologic spectrum of post-RTX CVID-like enteropathy encompasses lamina propria plasma cell depletion, increased crypt apoptotic bodies, small bowel villous atrophy, and goblet cell loss. While the underlying pathophysiology remains uncertain, the clinicopathologic picture may reflect post-RTX B-cell/plasma cell impairment. Although histologic findings may be subtle and variable, pathologists should be aware of this entity and should seek a history of RTX use in patients whose biopsies exhibit these CVID enteropathy-like features.

Climate change-induced environmental stressors, including ambient particulate matter (PM_2.5) and extreme heat stress (HS), pose serious health risks, particularly for neurodegenerative diseases. PM_2.5 exacerbates cardiovascular and neurodegenerative conditions, while HS increases mortality and worsens air pollution. Combined exposure may amplify these effects, especially in vulnerable populations at risk for Alzheimer's disease (AD). In our experimental study using a mouse model of early-onset Alzheimer's disease (EOAD), we explored the combined effects of extreme weather conditions, particularly exposure to ambient PM_2.5 and HS. Our research indicated that even short, repeated exposure to these environmental stressors disrupts brain energy metabolism and mitochondrial respiratory functions, which we found to be associated with altered hippocampal synaptic functions. Additionally, we find that key mechanisms associated with impaired intestinal permeability and gut dysbiosis are affected, supporting the hypothesis that exposure to climate change communication may also disrupt the gut-brain axis, as in part evidenced in our study by peripheral changes in immune and inflammatory signaling. Moreover, despite significant disruptions in metabolic and immune-inflammatory pathways, we observed no acceleration of cognitive decline in the young asymptomatic EOAD mice subjected to short, repeated exposure to extreme heat and environmental PM_2.5. These findings highlight the potential role of climate change in promoting risk factors like neuroinflammation and gut-brain axis dysfunction due to gut microbiome dysbiosis in the onset and progression of AD, particularly in asymptomatic individuals at risk for developing the condition.