Citations

AbstractINTRODUCTIONBlood‐based biomarkers offer a promising approach for the detection of neuropathologies from repetitive head impacts (RHI). We evaluated plasma biomarkers of amyloid, tau, neurodegeneration, and inflammation in former football players.METHODSThe sample included 180 former football players and 60 asymptomatic, unexposed male participants (aged 45–74). Plasma assays were conducted for beta‐amyloid (Aβ) 40, Aβ42, hyper‐phosphorylated tau (p‐tau) 181+231, total tau (t‐tau), neurofilament light (NfL), glial fibrillary acidic protein (GFAP), interleukin‐6 (IL‐6), Aβ42/p‐tau181 and Aβ42/Aβ40 ratios. We evaluated their ability to differentiate the groups and associations with RHI proxies and traumatic encephalopathy syndrome (TES).RESULTSP‐tau181 and p‐tau231(padj = 0.016) were higher and Aβ42/p‐tau181 was lower(padj = 0.004) in football players compared to controls. Discrimination accuracy for p‐tau was modest (area under the curve [AUC] = 0.742). Effects were not attributable to AD‐related pathology. Younger age of first exposure (AFE) correlated with higher NfL (padj = 0.03) and GFAP (padj = 0.033). Plasma GFAP was higher in TES‐chronic traumatic encephalopathy (TES‐CTE) Possible/Probable (padj = 0.008).DISCUSSIONPlasma p‐tau181 and p‐tau231, GFAP, and NfL may offer some usefulness for the characterization of RHI‐related neuropathologies.Highlights Former football players had higher plasma p‐tau181 and p‐tau231 and lower Aβ42/ptau‐181 compared to asymptomatic, unexposed men. Younger age of first exposure was associated with increased plasma NfL and GFAP in older but not younger participants. Plasma GFAP was higher in participants with TES‐CTE possible/probable compared to TES‐CTE no/suggestive.

AbstractNon‐neuroendocrine tumors account for around 10% of all primary neoplasms of the sella. If meningiomas, craniopharyngiomas, and germ cell tumors are excluded, the remaining lesions include a broad spectrum of uncommon, benign, and aggressive, often diagnostically challenging lesions. This review aims to summarize the essential clinicopathological features of tumors of the posterior pituitary gland, infundibulum spectrum expressing thyroid transcription factor 1, and primary sellar atypical rhabdoid teratoid tumor, and provide the criteria for their diagnosis and management.

Severe Communication Delays are Independent of Seizure Burden and Persist Despite Contemporary Treatments in SCN1A+ Dravet Syndrome: Insights From the ENVISION Natural History Study Perry MS, Scheffer IE, Sullivan J, Brunklaus A, Boronat S, Wheless JW, Laux L, Patel AD, Roberts CM, Dlugos D, Holder D, Knupp KG, Lallas M, Phillips S, Segal E, Smeyers P, Lal D, Wirrell E, Zuberi S, Brünger T, Wojnaroski M, Maru B, O'Donnell P, Morton M, James E, Vila MC, Huang N, Gofshteyn JS, Rico S. Epilepsia . 2024 Feb;65(2):322–337. Epub 2023 Dec 22. PMID: 38049202. doi: 10.1111/epi.17850 Objective: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. Methods: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). Results: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = 0.0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [0.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, P = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. Significance: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.

Objective: To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock. Data Sources: Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched. Study Selection: Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate. Data Extraction: Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials. Data Synthesis: Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50–0.85), shorter length of hospital stay (MD: −3.76 days, 95% CI: −6.66 to −0.86), and shorter pediatric intensive care unit length of stay (MD −2.34 days, 95% CI: −3.14 to −1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence. Conclusions: While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.

AbstractThe study objective was to compare the length of stay (LOS) and the proportion of one-night admissions before and after the implementation of an endocrine monitoring protocol following endoscopic transsphenoidal surgery (ETSS) for pituitary adenoma.Patients who underwent transsphenoidal pituitary adenoma resection between July 1, 2018, and September 9, 2022, were identified, and divided into two cohorts before and after the implementation of the monitoring protocol. The overall LOS and number of nights of admission were recorded. Readmission within 30 days after surgery was also recorded. The number of outpatient laboratory tests performed and the time to the first test were also noted.Thirty patients were identified in the preprotocol group and 60 in the postprotocol group. The average admission length in the preprotocol group was significantly longer than the average admission length in the postprotocol group (2.4 vs. 1.7 days, p = 0.004). The percentage of one-night admissions increased from 13 to 57% (p < 0.001). There were no significant differences in readmission rates between the two groups (p = 0.681). The number of laboratory encounters increased from a mean of 1.38 to 2.40 (p = 0.030), while the time to the first test decreased from a mean of 3.43 to 2.36 days (p = 0.049).Patients admitted after ETSS for pituitary adenoma had shorter hospital stay and greater proportion of one-night admission with the implementation of an endocrine monitoring protocol. The all-cause readmission rate was not statistically different between the two groups. Through aggressive outpatient laboratory monitoring, one-night admission for ETSS may be feasible.

Abstract ➤ The COVID-19 pandemic created a persistent surgical backlog in elective orthopedic surgeries. ➤ Artificial intelligence (AI) uses computer algorithms to solve problems and has potential as a powerful tool in health care. ➤ AI can help improve current and future orthopedic backlogs through enhancing surgical schedules, optimizing preoperative planning, and predicting postsurgical outcomes. ➤ AI may help manage existing waitlists and increase efficiency in orthopedic workflows.

363 Background: The incidence of BC in young adults is increasing; given their extended survivorship, characterizing healthcare utilization and adherence to surveillance guidelines can inform unmet health needs and gaps in care. Methods: The multi-center Young Women’s BC Cohort Study enrolled 1302 women ≤40 yrs with newly diagnosed (dx) BC from 2006-2016. Participants completed surveys every 6 mos for 3 yrs post-dx, then annually. The current analysis includes patients with Stage 0-III BC without recurrence who completed the 7-yr survey assessing survivorship care, including types of providers visited, BC surveillance, and other health maintenance practices. Multivariate logistic regression evaluated factors (clinical, demographics, concern about recurrence) associated with 1) full transition to a primary care provider (PCP) for follow-up; adherence to 2) mammography (among women who had a unilateral mastectomy or lumpectomy) and 3) bone density scans (among current hormonal therapy [HT] users), per ASCO/ACS guidelines. Results: Of 660 women with Stage 0-III BC, median age at dx was 37 (range: 17-40); 89% identified as White, 5%, Asian, 3%, Black, 3% as other/multiracial, and 4%, Hispanic. Most had received chemotherapy (75%) and radiation (61%) and 35% reported current HT; 12% had a BRCA1/2 mutation. For cancer-related follow-up, 57% reported seeing an oncology provider only, 12%, PCP only, and 29% saw a PCP + oncology provider. Among women with remaining breast(s) (n=348), 90% reported a mammogram in the last year. Adherence to other health maintenance practices varied: 68% reported having had a flu shot, 76% a pap test/pelvic exam, and 56% cholesterol screening within the last 2 yrs. Among current HT users (n=210), 46% reported a bone density scan within the last 2 yrs. In multivariate analyses assessing the odds of seeing a PCP only (vs. oncology + PCP), having stage 0 vs I disease (OR 2.74 95% CI 1.01-6.80) was associated with higher odds while any HT use (OR .31 95% CI .16-.58) and concern about recurrence (OR .23 95% CI .12-.47) were associated with lower odds. The table includes factors significantly associated with non-adherence to mammography and bone density scans. Conclusions: At 7-years post-dx, most young survivors participating in a cohort study receive cancer follow-up care from an oncology provider and have not fully transitioned their care to a PCP. Adherence to recommendations related to bone health among HT users was suboptimal. Additional research to identify barriers/facilitators to receipt of guideline-concordant follow-up care at the patient, provider, and systems levels may inform strategies to optimize survivorship in young BC survivors. Multivariable analysis: factors associated with non-adherence. MammogramOR 95% CI Bone density scanOR 95% CI Her2+ .38, .15 -.98 NS BRCA1/2 + 8.36, 1.38-50.47 .17, .05 -.62 Chemotherapy NS .22, .06 -.78 Unilateral mastectomy vs lumpectomy 6.64, 2.69-16.34 NS