Citations

Abstract The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP‐NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP‐NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP‐NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP‐NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP‐NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Importance Effects of antiamyloid agents, targeting either fibrillar or soluble monomeric amyloid peptides, on downstream biomarkers in cerebrospinal fluid (CSF) and plasma are largely unknown in dominantly inherited Alzheimer disease (DIAD). Objective To investigate longitudinal biomarker changes of synaptic dysfunction, neuroinflammation, and neurodegeneration in individuals with DIAD who are receiving antiamyloid treatment. Design, Setting, and Participants From 2012 to 2019, the Dominantly Inherited Alzheimer Network Trial Unit (DIAN-TU-001) study, a double-blind, placebo-controlled, randomized clinical trial, investigated gantenerumab and solanezumab in DIAD. Carriers of gene variants were assigned 3:1 to either drug or placebo. The present analysis was conducted from April to June 2023. DIAN-TU-001 spans 25 study sites in 7 countries. Biofluids and neuroimaging from carriers of DIAD gene variants in the gantenerumab, solanezumab, and placebo groups were analyzed. Interventions In 2016, initial dosing of gantenerumab, 225 mg (subcutaneously every 4 weeks) was increased every 8 weeks up to 1200 mg. In 2017, initial dosing of solanezumab, 400 mg (intravenously every 4 weeks) was increased up to 1600 mg every 4 weeks. Main Outcomes and Measures Longitudinal changes in CSF levels of neurogranin, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3–like 1 protein (YKL-40), glial fibrillary acidic protein (GFAP), neurofilament light protein (NfL), and plasma levels of GFAP and NfL. Results Of 236 eligible participants screened, 43 were excluded. A total of 142 participants (mean [SD] age, 44 [10] years; 72 female [51%]) were included in the study (gantenerumab, 52 [37%]; solanezumab, 50 [35%]; placebo, 40 [28%]). Relative to placebo, gantenerumab significantly reduced CSF neurogranin level at year 4 (mean [SD] β = −242.43 [48.04] pg/mL; P < .001); reduced plasma GFAP level at year 1 (mean [SD] β = −0.02 [0.01] ng/mL; P = .02), year 2 (mean [SD] β = −0.03 [0.01] ng/mL; P = .002), and year 4 (mean [SD] β = −0.06 [0.02] ng/mL; P < .001); and increased CSF sTREM2 level at year 2 (mean [SD] β = 1.12 [0.43] ng/mL; P = .01) and year 4 (mean [SD] β = 1.06 [0.52] ng/mL; P = .04). Solanezumab significantly increased CSF NfL (log) at year 4 (mean [SD] β = 0.14 [0.06]; P = .02). Correlation analysis for rates of change found stronger correlations between CSF markers and fluid markers with Pittsburgh compound B positron emission tomography for solanezumab and placebo. Conclusions and Relevance This randomized clinical trial supports the importance of fibrillar amyloid reduction in multiple AD-related processes of neuroinflammation and neurodegeneration in CSF and plasma in DIAD. Additional studies of antiaggregated amyloid therapies in sporadic AD and DIAD are needed to determine the utility of nonamyloid biomarkers in determining disease modification. Trial Registration ClinicalTrials.gov Identifier: NCT04623242

Abstract Background In 2021, the state of Arizona experienced the largest focal outbreak of West Nile virus (WNV) in US history. Timely and accurate diagnostic testing remains a challenge for WNV due to transient viremia and limited immunoassay specificity. Recent studies have identified whole blood (WB) and urine as more sensitive specimen types for the detection of WNV RNA. Methods We evaluated ordering practices, test performance, and patient characteristics of probable and confirmed cases. In total, we identified 190 probable and proven cases, including 127 patients (66.8%) with neuroinvasive disease. Results Among all cases, only 29.5% had WNV polymerase chain reaction (PCR) testing ordered on WB, of which 80.3% resulted as positive, including 7 cases in which WNV serologic testing was negative and 5 cases for which serologic testing was not ordered. In comparison, only 23.7% of cases that had cerebrospinal fluid (CSF) PCR ordered had a positive result, including 3 cases that were negative by PCR on WB. In contrast, WNV PCR on WB detected 12 neuroinvasive cases that were CSF PCR negative. WNV PCR testing in urine was only ordered on 2 patients, both of whom were positive. Crossing cycle threshold (Ct) values were not significantly different between WB and CSF specimen types, nor was there a correlation between Ct value and days from symptom onset at the time of sample collection; all specimen types and time points had Ct values, with 98% above 30. WB was positive by WNV PCR in several patients for >7 days (range, 7–25 days) after symptom onset, as was the CSF PCR. Conclusions Taken together, these findings indicate that WNV PCR testing on WB may be the best initial test for timely diagnosis of WNV infection, irrespective of clinical manifestation; however, if negative in patients with suspected neuroinvasive disease, WNV PCR testing on CSF should be ordered.

Introduction: Perceived discrimination is known to play a role in the development of cardiovascular (CV) risk factors such as hypertension, but the association with CV outcomes is less clear. A recent report from a multi-ethnic cohort study found a modestly increased risk of CV disease in participants reporting discrimination. We explored this association in an African American (AA) cohort. Hypothesis: Greater perceived discrimination is associated with a higher risk of CV disease Methods: We examined CV outcomes among 5085 AAs in the Jackson Heart Study enrolled in 2000-2004 and followed through December 31, 2012. We stratified participants by quartiles of perceived everyday discrimination and estimated the associations with CV outcomes (all-cause mortality, incident coronary heart disease [CHD], incident stroke, and heart failure [HF] hospitalization) using Cox models. Results: Greater perceived discrimination was more common in participants who were younger, male, had higher education and income, a lower perceived standing in the community, worse perceived healthcare access, and fewer comorbidities. Over a median follow-up of 9.8 years (8.0 years for HF), 573 deaths, 193 incident CHD, 156 incident strokes, and 348 HF hospitalizations occurred. Prior to adjustment, greater perceived discrimination was associated with a lower risk of death, incident CHD, stroke, and HF hospitalization (Table). After adjustment for potential confounders, we found no association of perceived discrimination with incident CHD, stroke or HF hospitalization; however, a decrease in all-cause mortality risk with higher perceived discrimination persisted. Conclusions: We found no independent association of perceived discrimination with risk of incident CV disease or HF hospitalization and a paradoxical negative association with mortality in this AA population. The unexpected finding of a lower risk of death with greater perceived discrimination requires further study.

BACKGROUND COVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined. METHODS This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization–equivalent anti–Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis. RESULTS SARS-CoV-2 anti–S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01). CONCLUSION In unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors’ antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use. TRIAL REGISTRATION ClinicalTrials.gov NCT04373460. FUNDING Department of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Background: Breastfeeding has numerous health benefits for patients and their infants. There are inconsistencies in how anesthesia providers care for lactating patients undergoing anesthesia. Providers may be cautious and have patients “pump and dump” instead of following current evidence-based recommendations. Video-based education provides a novel reference for health care providers in their fast-paced work environments. This project evaluated the effectiveness of an online video module and resources accessed at the bedside for anesthesia providers caring for lactating patients. Materials and Methods: A preintervention survey was sent to anesthesia providers at a large academic institution to assess baseline knowledge of current recommendations for caring for lactating patients having anesthesia. A quick response code-linked video module and references were created and disseminated to all anesthesia providers. A postsurvey was sent to assess knowledge and satisfaction with the educational approach. Postsurvey data were compared with presurvey data. Results: All who watched the educational video found the education helpful to care for lactating patients undergoing surgery. In the posteducation group, 93% of providers selected the correct recommendation to continue breastfeeding or pumping after general anesthesia or sedation once the patient is awake and alert, compared with 48% in the pre-education group. After education, 92% would recommend preoperative feeding or pumping prior to transport to the operating room, compared with the 50% in the pre-education group. Conclusions: Video-based, just-in-time education is an effective way to deliver updated information to anesthesia providers. This format is conducive to just-in-time delivery, and there may be implications for other patient populations that present infrequently but require population-specific care.

Objective To report epidemiological data regarding injury and illness among the Team USA staff during the Tokyo 2020 Summer Olympic and Paralympic Games and Beijing 2022 Winter Olympic and Paralympic Games. Methods A retrospective review of all Team USA staff (total staff, N=1703 (62.5% female); total staff days (SD)=34 489) medical encounters during the Tokyo 2020 Games and Beijing 2022 Games was conducted. Details related to injury and illness were evaluated. Incidence with 95% CI per 1000 staff days were calculated. Results A total of 32 illnesses (incidence [95% CI] 0.9 [0.6, 1.2]) and 23 injuries (incidence 0.7 [0.4, 0.9]) were sustained by the Team USA delegation staff members during the Tokyo 2020 Games and Beijing 2022 Games. Female staff reported more illnesses (illnesses proportion (IP) 2.9%; incidence 1.4 [0.8, 2.0]), while male staff incurred more injuries (IP 1.8%; incidence 0.9 [0.5, 1.3]). When stratified by physiological system, dermatological and infectious were the most common systems involved with illness (IP 0.5%; incidence 0.2 [0.1, 0.4]). Injuries to the upper limb were most common (IP 0.3%; incidence 0.3 [0.1, 0.5]). Conclusion Injury and illness rates among the Team USA staff during the Tokyo 2020 Games and Beijing 2022 Games were low, but notable. Knowledge of injury and illness risks contributes to staffing decisions and prevention strategies for staff supporting athletes during competition.

ABSTRACT Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials. Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm, or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.