Mountain Home VA Healthcare System

Traumatic brain injury (TBI) causes neuroinflammation and can generate long-term pathological consequences, including motor and visual impairments, cognitive deficits, and depression. In our previous study, we found that Fat1+-transgenic mice with higher endogenous n-3 polyunsaturated fatty acids (n-3 PUFA) were protected from post-TBI behavioral deficits and exhibited reduced levels of TBI-induced microglial activation, inflammatory factors, and sphingolipid ceramide, a lipid mediator of inflammation and cell death. This study’s objective was to evaluate if feeding n-3 PUFA (EPA and docosahexaenoic acid, DHA 2:1) could restrict the elevation of ceramide in brain tissue and prevent TBI-mediated sensory-motor and behavioral deficits. Wildtype C57/BL6 mice were gavage pre-fed with PUFA (EPA: DHA = 2:1) at 500 mg/kg body weight/week for 2 weeks before and 4 weeks after exposure to left side focal cranial air-blast (50 psi) TBI or sham-blast (0-psi). Saline-gavaged mice served as controls. Following blast injury, various motor, visual, and behavioral tests were conducted, and brain tissues were collected for histological and biochemical assays. Lipidomics analysis confirmed a significant elevation of EPA in the plasma and brain tissue of PUFA-fed mice. TBI-Blast brain tissues were found to have elevated ceramide levels in control mice but not in PUFA-fed mice. Moreover, PUFA-fed mice demonstrated protection against motor impairment, photoreceptor dysfunction, depression, oculomotor nerve degeneration, and microglia activation in the optic tract. Our results demonstrate that EPA-mediated suppression of ceramide biosynthesis and neuroinflammatory factors in PUFA-fed mice is associated with significant protection against the visual, motor, and emotional deficits caused by TBI.

Introduction The Janssen Ad26.COV2.S vaccine was developed to prevent SARS-CoV-2 illness. Phase 3 trials were initiated in 2020, including sites at the University of Kentucky, Norton Healthcare Louisville, and Baptist Health Lexington. This study followed non-immunosuppressed adult subjects through July 2022 to evaluate vaccine efficacy and safety, with a total of 1,094 participants. Methods Subjects aged 18 years or older, in good health, and without major immunological conditions were included. Three trials (ENSEMBLE-1, ENSEMBLE-2, and AMPLIFY) were conducted. Participants were evaluated for vaccine efficacy if they were nucleocapsid antibody-negative and had no prior COVID-19 infection at the time of their first booster. Vaccine regimens included a prime and single boost with Ad26.COV2.S or other combinations of prime and boost vaccinations, including mRNA vaccines. Results A total of 1,094 subjects were enrolled, with 903 subjects evaluated for vaccine efficacy. Among these, 431 received only a prime and single boost with Ad26.COV2.S, and 472 received other combinations of vaccines. During the study period, 174 COVID-19 infections occurred, with 95 (55%) being asymptomatic. The incidence of infections was similar between those who received only Ad26.COV2.S (94 infections) and those with other vaccination regimens (80 infections), with no significant difference (P > .05). There were no serious vaccine-related safety concerns, and only one hospitalization occurred, involving a 75-year-old diabetic who recovered without intubation. Conclusion The Ad26.COV2.S vaccine, as a prime and single boost, demonstrated similar efficacy to other vaccination regimens in preventing COVID-19 infections. Both regimens provided protection against severe disease and hospitalization, with no significant safety concerns identified. This study supports the effectiveness and safety of the Ad26.COV2.S vaccine in the adult population during a period of high COVID-19 incidence.

Introduction: A member of the herpes virus family, Epstein Barr virus (EBV) is one of the most common human viruses. It can cause latent infections in humans, leading to serious health complications, including lymphomas and lymphoproliferative disorders. Mucocutaneous ulcers associated with EBV (EBVMCU) are a recently established entity of the lymphoproliferative disorders in 2010. Case Description/Methods: An 82-year-old male with Crohn's disease s/p right hemicolectomy with the formation of neo-ileum seven years earlier, bladder cancer, lung cancer s/p lobectomy in remission for both cancers. He presented to the hospital complaining of bright red blood per rectum. He reports chronic loose stools attributed to a history of Crohn's disease and right hemicolectomy seven years earlier when 30 cm colon was removed, including terminal ileum to the proximal transverse colon. The patient reports that he believed his Crohn's was never symptomatic and was worried about the side effects of biologic Crohn's treatment, which he refused in the past. Colonoscopy revealed extensive ulceration at the neo-ileum with friable mucosa. The histology shows scattered large atypical EBV-positive cells of B cell lineage in inflamed and ulcerated mucosa with granulation tissue. A definitive diagnosis could not be made, and further biopsies were recommended. PET scan and CT scan were unremarkable for metabolically active malignant lesions or lymphadenopathy. Colonoscopy repeated two months later showed the same ulcerated lesion with the same histological features mentioned earlier. (Figure) Discussion: EBVMCUs manifest as shallow sharply circumscribed ulcers on the mucosa or skin and are histologically distinguished by the proliferation of variable-sized, atypical B-lymphocytes, making the site of the ulcers in the neo-ileum very atypical and unique. The lesion usually develops in individuals with impaired immunity, such as those who are elderly, have iatrogenic immunosuppression, have primary immune disorders, or are HIV/AIDS-infected. The lack of a tumor mass favors an EBV-positive mucocutaneous ulcer, a newly recognized entity that can involve the GIT and occurs as an age-related disease and in immunosuppressed patients. In contrast to other EBV-related lymphoproliferative disorders, such as EBV-positive diffuse large B-cell lymphoma, EBVMCU has a good prognosis. A watch-and-wait approach or reduction in immunosuppressants are usually sufficient to cause EBVMCU patients to achieve remission.Figure 1.: Neo-ileum biopsy: The atypical cells are large with ovoid to irregular nuclear membrane, hyperchromatic nuclei, variable prominent nucleoli, and cytoplasmic clearing.

Introduction: Studies have shown decrease rates of restenosis and target lesion revascularization (TLR) with drug eluting balloon (DEB) in diabetic patients with critical limb ischemia (CLI). Hypothesis: The aim of this meta-analysis to compare the efficacy of DEB versus Percutaneous transluminal angioplasty (PTA) below the knee peripheral intervention. Methods: Electronic databases including MEDLINE, ClinicalTrials.gov and the Cochrane Library were searched for all randomized controlled trials (RCTs) published until April 2020 comparing outcomes of DEB vs PTA in patients with CLI below the knee. End points were major amputation, major adverse events (MAEs), all-cause mortality, target lesion revascularization (TLR), myocardial infarction, and cerebrovascular accidents (CVA). The risk ratio (RR) with 95% confidence interval (CI) were computed and p <0.05 was considered as a level of significance. Results: A total of 4 RCTs (n=655) were included in the final analysis. There were no differences of major amputation (RR: 1.30; CI: 0.68-2.46; p=0.43), MAEs (RR: 0.86; CI: 0.60-1.23; p=0.41), all-cause mortality (RR: 0.91; CI: 0.69-1.19; p=0.48), TLR (RR: 0.65; CI: 0.30-1.44; p=0.29), MI (RR: 1.71; CI: 0.57-5.14; p=0.34) and CVA (RR: 0.66; CI: 0.19-2.26; p=0.50) between the 2 groups [Figure 1]. Conclusions: There were no significant differences of major amputation and TLR for DEB versus PTA . Major adverse cardiac, cerebrovascular events and all-cause mortality were not statistically different for drug coated balloon versus PTA in the management of below knee critical limb ischemia. Further studies needed to confirm these findings.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder characterized by a mutation of the neurofibromin 1 (NF1) gene, resulting in increased susceptibility for multiple tumors, namely, gastrointestinal stromal tumors (GISTs)—the most common types of mesenchymal neoplasms in the gastrointestinal tract. Despite these tumors' predilection for the stomach, it seems to be the least likely part of the gastrointestinal (GI) tract to be affected in cases of neurofibromatosis. Herein, we report a case of a 61-year-old male patient with known neurofibromatosis, who presented with acute blood loss anemia due to a recurrent gastric GIST, requiring partial gastrectomy due to its size and multiple recurrences.

Barry, Neil1; Sutherland, Michael1; Modi, Fagunkumar2; Byrd, Ryland3; Roy, Thomas1 Author Information

Veterans of the armed forces, like most population groups, have a high prevalence of vitamin D deficiency, which may be associated with adverse outcomes in several types of cancer. Ultraviolet irradiation is inversely linked with the risk of bladder cancer, presumably through enhanced vitamin D synthesis. We hypothesized that variations in vitamin D status and monitoring predict adverse outcomes in bladder cancer among veterans. A retrospective analysis of data in the Veterans Integrated Service Network-9 (southeastern United States) was performed for patients diagnosed between October 1, 1999 and February 29, 2008. Age, tobacco exposure, body mass index, and latitude and seasonality of sampling were included as variables in addition to serum vitamin 25(OH)D levels. Monitoring of vitamin D and vitamin D levels and status were closely linked to survival in bladder cancer. Both the chances of survival and longevity improved with enhanced vitamin D status and monitoring. Veterans with bladder cancer had better outcomes if the initial vitamin D level was higher and had more monitoring of the vitamin. Initial vitamin D levels were more strongly related to outcomes than follow-up levels. The link between vitamin D and outcomes remained after adjusting for background variables such as age, body mass index, latitude, seasonality, and tobacco exposure. Findings suggest that adequate vitamin D levels early in the course of the disease provide the best opportunity to improve outcomes. Ensuring that veterans with bladder cancer have adequate vitamin D reserves with appropriate monitoring may play a role in improving outcomes in bladder cancer.