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BACKGROUND AND OBJECTIVES: Cerebrovascular reactivity (CVR) represents the ability of cerebral blood vessels to regulate blood flow in response to vasoactive stimuli and is related to cognition in cerebrovascular and neurodegenerative conditions. However, few studies have examined CVR in the medial temporal lobe, known to be affected early in Alzheimer disease and to influence memory function. We aimed to examine whether medial temporal CVR is associated with memory function in older adults with and without mild cognitive impairment (MCI). METHODS: In this observational study, independently living older adults free of dementia or stroke were recruited from the community and underwent brain MRI, neuropsychological assessment, and blood draw in an academic research setting. pCASL MRI quantified medial temporal lobe cerebral perfusion during CVR response to hypercapnia. Hypercapnia was induced by visually guided breathing exercises (15 seconds breath holds) during capnographic monitoring. MCI diagnosis and memory performance were assessed through comprehensive neuropsychological assessment. Aβ42/40 and pTau181 levels were quantified in blood plasma. Logistic and hierarchical linear regression examined medial temporal CVR in relation to MCI diagnosis and memory function. RESULTS: In a sample of 144 older adults (mean age = 69.6 years; SD = 7.4%; 34.7% male; mean education = 16.6 years, SD = 2.3), CVR to hypercapnia in the medial temporal lobe was attenuated in individuals with MCI after adjusting for age, sex, education, apolipoprotein ε4 carrier status, Aβ42/40 and pTau181 levels, and vascular risk factors (OR = 0.87, 95% CI [0.77-0.97], p = 0.013). Cerebrovascular reactivity to hypercapnia was associated with verbal memory performance for stories (B = 0.33, 95% CI [0.09-0.57], p = 0.009), a word list (B = 0.10, 95% CI [0.001-0.20], p = 0.048), and visual memory (B = 0.33, 95% CI [0.09-0.57], p = 0.008). DISCUSSION: Deficits in medial temporal CVR are observed in older adults with MCI and are related to worse memory function. Findings suggest that medial temporal cerebrovascular dysfunction is related to cognition and memory before the onset of dementia, independent of changes in Alzheimer pathophysiologic markers. Limitations of the study include the cross-sectional design. Future longitudinal studies are warranted to examine whether early cerebrovascular changes can predict progressive memory decline.

BackgroundThis study compares positive margin rates in breast conserving surgery (BCS) for early breast cancer using two localization techniques: surgeon-performed intraoperative ultrasound-guided wire localization (IOWL) versus radiologist-performed preoperative wire localization (POWL).MethodsPatients with unifocal breast cancer undergoing BCS with follow-up at a single institution were retrospectively identified. Factors associated with positive margins were identified.Results177 patients underwent IOWL (N ​= ​85) or POWL (N ​= ​92). There was a significantly lower rate of positive margins for IOWL vs. POWL (7.1 ​% vs. 23.9 ​%, p ​= ​0.002) and a corresponding lower rate of re-excision for IOWL vs. POWL (5.9 ​% vs. 18.5 ​%, p ​= ​0.011). Presence of DCIS was associated with positive margins (p ​= ​0.015). After adjusting for presence of DCIS, tumor size, and volume of tissue removed, the positive margin rate was significantly lower in the IOWL group compared to the POWL group (aOR 0.34, 95 ​% CI 0.13-0.93).ConclusionsIn this study, adjusted analysis favored IOWL in achieving negative tumor margins. Prospective studies are needed to further explore the impact of IOWL on quality, cost-effectiveness, and patient experience.

We hypothesized that the inferior disease-free survival (DFS) seen in older patients who underwent αβ-T-cell/CD19-depleted (AB-TCD) haploidentical hematopoietic cell transplantation (HCT) for hematologic malignancies is caused by excessive exposure to rabbit antithymocyte globulin (rATG; Thymoglobulin). Between 2015 and 2023, 163 patients with a median age of 13 years (range, 0.4-27.4) underwent AB-TCD haploidentical HCT for the treatment of acute lymphoblastic leukemia (n = 98), acute myeloid leukemia/myelodysplastic syndrome (n = 49), or other malignancies (n = 16) at 9 centers in 2 prospective trials. Exposures to rATG before and after HCT were predicted using a validated pharmacokinetic model. Receiver operating characteristic curves were used to identify the optimal target windows for rATG exposure in terms of outcomes. We identified 4 quadrants of rATG exposure, namely quadrant 1 (n = 52) with a high pre-HCT area under curve (AUC; ≥50 arbitrary units [AU] per day per milliliter) and a low post-HCT AUC (

Owing to an exponential increase in the number of courses offered online, it is crucial to understand this mode of delivery on a deeper level. In this study, associations among course performance, the use of online resources (i.e., online homework assistance, practice questions and practice tests), mode of delivery (online versus in-person), and session length (Fall/Winter for 8 months versus Spring/Summer for 10 weeks) were examined. Archival data were used from an educational website for an introductory statistics course at a medium-sized Canadian university. Anonymized data were retrieved from 738 students enrolled in the course between 2018 and 2021. Course performance was measured by final course grades and use of resources was assessed in terms of the number of site visits and downloads. It was found that use of online resources was significantly and positively correlated with course performance. However, session length and mode of delivery did not yield significant differences in terms of final course grades. Future studies could examine potential moderators in the relationships between the use of resources with the session length, the delivery method, and course performance to see the effectiveness of the resources in various course delivery models (in-person, hybrid, synchronous online, asynchronous online, etc.).

C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9-19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.

BACKGROUND: After treatment of pregnancy-associated breast cancer (PABC), some women desire future pregnancy. While safety of pregnancy after breast cancer has been demonstrated, the same cannot be said about women with PABC. OBJECTIVE: The aim of this study was to describe the incidence and outcomes of patients with PABC with subsequent pregnancies compared with those without another pregnancy. METHODS: A retrospective chart review identified patients diagnosed with breast cancer during pregnancy or within 5 years postpartum between 2011 and 2023. Patients were then screened for further pregnancy. Clinicopathologic variables, oncologic outcomes, and pregnancy outcomes were recorded. The Chi-square test and t-test were used to compare patients with subsequent pregnancy with those without. Kaplan-Meier method and log-rank test were used to estimate 5-year disease-free survival (DFS). RESULTS: Overall, 75 patients with PABC were identified, 58 of whom had PABC and no further pregnancies (NSP-PABC) and 17 with subsequent pregnancy (SP-PABC). Compared with patients with NSP-PABC, patients with SP-PABC were significantly younger (p = 0.015) and less likely to have prior pregnancies (p

IntroductionIn academic breast surgery, ultrasound use tends to be limited to radiology departments, thus formal surgical resident training in breast ultrasound is sparse. Building on residents' ultrasound skills in our general surgery training program, we developed a novel curriculum to teach ultrasound-guided breast procedures (UGBPs), including core needle biopsy (CNB) and wire localization (WL). We hypothesized that learning UGBPs on cadavers would be preferred to learning with a breast phantom model using chicken breasts.MethodsResidents received a 1-h lecture on breast CNB and WL followed by a 1-h hands-on laboratory session. Olives stuffed with red pimentos were used to replicate breast masses and implanted in chicken breasts and the breasts of lightly embalmed and unembalmed female cadavers. All residents practiced UGBPs with a course instructor on both models. Residents completed anonymous prelaboratory and postlaboratory surveys utilizing five-point Likert scales.ResultsA total of 35 trainees participated in the didactics; all completed the prelaboratory survey and 28 completed the postlaboratory survey. Participant clinical year ranged from 1 to 6. Residents' confidence in describing and performing CNBs and WLs increased significantly on postlaboratory surveys, controlling for clinical year (P

PURPOSE: Adding pembrolizumab to neoadjuvant chemotherapy (NAC) for triple-negative breast cancer (TNBC) improves pathologic complete response (pCR) rates and event-free survival. The impact of adding immunotherapy to NAC on surgical outcomes is unknown. This study compares 90-day post-surgical complications (PSCs) and time to adjuvant treatment among patients undergoing NAC for TNBC with and without immunotherapy. METHODS: Patients treated with NAC alone or with immunotherapy (NAC-I) for stage I-III TNBC between 2018 and 2022 were retrospectively identified at a single academic institution. Kruskal-Wallis rank sum and Fishers exact tests compared patient sociodemographic and clinical characteristics. Multivariable logistic regression determined odds ratios (OR) predicting PSCs. RESULTS: Of 54 patients, 29 received NAC alone and 25 received NAC-I. Compared to NAC patients, NAC-I patients had more advanced stage tumors (p = 0.038), and had slightly higher rates of mastectomy with reconstruction (p = 0.193). 72.0% of NAC-I patients experienced a pCR, compared with 44.8% of NAC patients (p = 0.193). There were 10 PSCs (34.5%) in NAC patients compared to 9 PSCs (36.0%) in NAC-I patients (p > 0.99). Regression analysis demonstrated no association of PSCs with NAC-I (OR 0.83, 95% CI 0.19-3.60). Time to adjuvant therapy was shorter for NAC-I patients (28 days vs 36 days, p = 0.013). CONCLUSIONS: Patients with TNBC receiving NAC-I have higher pCR rates and do not appear to have added 90-day PSCs or delays to adjuvant therapy despite trending toward more extensive surgical procedures compared to NAC alone. Larger studies are needed to further evaluate the surgical safety of immunotherapy.

BACKGROUND: Extreme Risk Protection Orders (ERPOs) are civil court orders that prohibit firearm purchase and possession when someone is behaving dangerously and is at risk of harming themselves and/or others. As of June 2024, ERPOs are available in 21 states and the District of Columbia to prevent firearm violence. This paper describes the design and protocol of a six-state study of ERPO use. METHODS: The six states included are California, Colorado, Connecticut, Florida, Maryland, and Washington. During the 3-year project period (2020-2023), ERPO case files were obtained through public records requests or through agreements with agencies with access to these data in each state. A team of over four dozen research assistants from seven institutions coded 6628 ERPO cases, abstracting 80 variables per case under domains related to respondent characteristics, events and behaviors leading to ERPO petitions, petitioner types, and court outcomes. Research assistants received didactic training through an online learning management system that included virtual training modules, quizzes, practice coding exercises, and two virtual synchronous sessions. A protocol for gaining strong interrater reliability was used. Research assistants also learned strategies for reducing the risk of experiencing secondary trauma through the coding process, identifying its occurrence, and obtaining help. DISCUSSION: Addressing firearm violence in the U.S. is a priority. Understanding ERPO use in these six states can inform implementation planning and ERPO uptake, including promising opportunities to enhance safety and prevent firearm-related injuries and deaths. By publishing this protocol, we offer detailed insight into the methods underlying the papers published from these data, and the process of managing data abstraction from ERPO case files across the multi-state and multi-institution teams involved. Such information may also inform future analyses of this data, and future replication efforts. REGISTRATION: This protocol is registered on Open Science Framework ( https://osf.io/kv4fc/ ).