Citations

Most studies on ketosis have focused on short-term effects, male athletes, or weight loss. Hereby, we studied the effects of short-term ketosis suppression in healthy women on long-standing ketosis. Ten lean (BMI 20.5 ± 1.4), metabolically healthy, pre-menopausal women (age 32.3 ± 8.9) maintaining nutritional ketosis (NK) for > 1 year (3.9 years ± 2.3) underwent three 21-day phases: nutritional ketosis (NK; P1), suppressed ketosis (SuK; P2), and returned to NK (P3). Adherence to each phase was confirmed with daily capillary D-beta-hydroxybutyrate (BHB) tests (P1 = 1.9 ± 0.7; P2 = 0.1 ± 0.1; and P3 = 1.9 ± 0.6 pmol/L). Ageing biomarkers and anthropometrics were evaluated at the end of each phase. Ketosis suppression significantly increased: insulin, 1.78-fold from 33.60 (± 8.63) to 59.80 (± 14.69) pmol/L (p = 0.0002); IGF1, 1.83-fold from 149.30 (± 32.96) to 273.40 (± 85.66) µg/L (p = 0.0045); glucose, 1.17-fold from 78.6 (± 9.5) to 92.2 (± 10.6) mg/dL (p = 0.0088); respiratory quotient (RQ), 1.09-fold 0.66 (± 0.05) to 0.72 (± 0.06; p = 0.0427); and PAI-1, 13.34 (± 6.85) to 16.69 (± 6.26) ng/mL (p = 0.0428). VEGF, EGF, and monocyte chemotactic protein also significantly increased, indicating a pro-inflammatory shift. Sustained ketosis showed no adverse health effects, and may mitigate hyperinsulinemia without impairing metabolic flexibility in metabolically healthy women.

Abstract In the development of various strategies of anti-CD19 immunotherapy for the treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant treatment with tafasitamab and CART19 showed major CD19 binding competition, which led to CART19 functional impairment. However, when CD19+ cell lines were pretreated with tafasitamab overnight and the unbound antibody was subsequently removed from the culture, CART19 function was not affected. In preclinical in vivo models, tafasitamab pretreatment demonstrated reduced incidence and severity of cytokine release syndrome and exhibited superior antitumor effects and overall survival compared with CART19 alone. This was associated with transient CD19 occupancy with tafasitamab, which in turn resulted in the inhibition of CART19 overactivation, leading to diminished CAR T apoptosis and pyroptosis of tumor cells.

ImportanceIntraductal papillary mucinous neoplasms (IPMNs) are pancreatic cysts that can give rise to pancreatic cancer (PC). Limited population data exist on their prevalence, natural history, or risk of malignant transformation (IPMN-PC).ObjectiveTo fill knowledge gaps in epidemiology of IPMNs and associated PC risk by estimating population prevalence of IPMNs, associated PC risk, and proportion of IPMN-PC.Design, Setting, and Participants: This retrospective cohort study was conducted in Olmsted County, Minnesota. Using the Rochester Epidemiology Project (REP), patients aged 50 years and older with abdominal computed tomography (CT) scans between 2000 and 2015 were randomly selected (CT cohort). All patients from the REP with PC between 2000 and 2019 were also selected (PC cohort). Data were analyzed from November 2021 through August 2023.Main outcomes and MeasuresCIs for PC incidence estimates were calculated using exact methods with the Poisson distribution. Cox models were used to estimate age, sex, and stage–adjusted hazard ratios for time-to-event end points.ResultsThe CT cohort included 2114 patients (1140 females [53.9%]; mean [SD] age, 68.6 [12.1] years). IPMNs were identified in 231 patients (10.9%; 95% CI, 9.7%-12.3%), most of which were branch duct (210 branch-duct [90.9%], 16 main-duct [6.9%], and 5 mixed [2.2%] IPMNs). There were 5 Fukuoka high-risk (F-HR) IPMNs (2.2%), 39 worrisome (F-W) IPMNs (16.9%), and 187 negative (F-N) IPMNs (81.0%). After a median (IQR) follow-up of 12.0 (8.1-15.3) years, 4 patients developed PC (2 patients in F-HR and 2 patients in F-N groups). The PC incidence rate per 100 person years for F-HR IPMNs was 34.06 incidents (95% CI, 4.12-123.02 incidents) and not significantly different for patients with F-N IPMNs compared with patients without IPMNs (0.16 patients; 95% CI, 0.02-0.57 patients vs 0.11 patients; 95% CI, 0.06-0.17 patients; P = .62). The PC cohort included 320 patients (155 females [48.4%]; mean [SD] age, 72.0 [12.3] years), and 9.8% (95% CI, 7.0%-13.7%) had IPMN-PC. Compared with 284 patients with non-IPMN PC, 31 patients with IPMN-PC were older (mean [SD] age, 76.9 [9.2] vs 71.3 [12.5] years; P = .02) and more likely to undergo surgical resection (14 patients [45.2%] vs 60 patients [21.1%]; P = .003) and more-frequently had nonmetastatic PC at diagnosis (20 patients [64.5%] vs 130 patients [46.8%]; P = .047). Patients with IPMN-PC had better survival (adjusted hazard ratio, 0.62; 95% CI, 0.40-0.94; P = .03) than patients with non-IPMN PC.Conclusions and RelevanceIn this study, CTs identified IPMNs in approximately 10% of patients aged 50 years or older. PC risk in patients with F-N IPMNs was low and not different compared with patients without IPMNs; approximately 10% of patients with PC had IPMN-PC, and they had better survival compared with patients with non-IPMN PC.

Case: A 25-year-old male pole vaulter presented with several months of right ankle pain. Radiographs showed an anterior tibial osteophyte with a small intra-articular body suggesting impingement. Weight-bearing computed tomography (CT) revealed an associated tibial plafond stress fracture. Subsequent arthroscopy with osteophyte resection and loose body removal significantly improved symptoms, and he gradually resumed training. Conclusion: Stress fractures should always be considered in athletes with ankle pain. A unique aspect of this case was the use of weight-bearing CT in diagnosis and surgical planning. To our knowledge, this is the first described case in which weight-bearing CT was used in this fashion.