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The brain contains an astronomical number of neurons, but it is their collective activity that underlies brain function. The number of degrees of freedom that this collective activity explores – its dimensionality – is therefore a fundamental signature of neural dynamics and computation (1–7). However, it is not known what controls this dimensionality in the biological brain – and in particular whether and how recurrent synaptic networks play a role (8–10). Through analysis of high-density Neuropixels recordings (11), we argue that areas across the mouse cortex operate in asensitive regimethat gives these synaptic networks a very strong role in controlling dimensionality. We show that this control is expressed across time, as cortical activity transitions among states with different dimensionalities. Moreover, we show that the control is mediated through highly tractable features of synaptic networks. We then analyze these key features via a massive synaptic physiology dataset (12). Quantifying these features in terms of cell-type specific network motifs, we find that the synaptic patterns that impact dimensionality are prevalent in both mouse and human brains. Thus local circuitry scales up systematically to help control the degrees of freedom that brain networks may explore and exploit.
Vulvar lichen sclerosus (LS) is a chronic inflammatory skin condition primarily affecting the anogenital region, leading to scarring, sexual dysfunction, and increased risk of squamous cell carcinoma. The pathophysiology involves immune-mediated fibrosis, causing architectural distortment and functional impairment. Women with LS frequently present with vulvar pain, pruritus, irritation, voiding dysfunction, and sexual dysfunction, with progressive scarring leading to conditions like clitoral phimosis and labial adhesions. Initial interventions typically include topical ultra high-potency corticosteroids, which have been shown to reverse some histological changes. However, surgical intervention, such as lysis of vulvar adhesions and clitoral phimosis surgery, is the sole therapeutic means of rectifying extensive scarring, restoring vulvar anatomy, and improving sexual function. This study aimed to evaluate the impact of surgical interventions, specifically lysis of vulvar adhesions and clitoral phimosis surgery, on sexual dysfunction and overall patient satisfaction in women with vulvar LS. A prospective pre-post intervention cohort study was conducted on patients treated at a vulvar disorders clinic from December 2003 to January 2024. Participants completed both pre- and postoperative assessments including the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), and descriptive response questions. Statistical analysis was performed to compare preoperative and postoperative outcomes, and thematic analysis was conducted on patient narratives to capture qualitative improvements. A total of 74 women (median age 46.9 ± 14.7 years) completed the follow-up survey. FSDS scores showed a substantial reduction from 32.77 (SD = 13.09) preoperatively to 16.75 (SD = 14.64) postoperatively (p < 0.0001), with 82.4% (47/57) reporting improved sexual distress. The mean FSFI score improved significantly from 14.5 (SD = 7.99) preoperatively to 19.6 (SD = 11.28) postoperatively (p = 0.007), with 71.9% (41/57) of women reporting an overall improvement in sexual function. Patient satisfaction was notably high, with 91.9% (68/74) reporting being either “very satisfied” or “satisfied,” and 85.1% (63/74) indicating they would recommend the surgery to others. Only 8.1% (6/74) expressed dissatisfaction with their surgical outcomes. A qualitative analysis of patient responses revealed key themes, including improved sexual function, pain reduction, and psychological relief. Many participants reported restored sexual confidence and reduced distress, while a minority expressed frustration due to recurrent symptoms. Postoperative complications were reported by 12.2% (9/74), with the most common being recurrent scarring (4.1%). Revision surgery was required in 9.5% (7/74) of cases, with significant improvements reported after all revision procedures. Patients with lichen sclerosus who undergo surgical management of vulvar adhesions report significant improvements in sexual function and distress, with high satisfaction rates. While a small subset of patients experienced complications or required revision surgeries, the overall positive outcomes support the procedure as an effective intervention for advanced LS. These results emphasize the need for tailored preoperative counseling and patient selection to optimize long-term success and patient satisfaction. No.
Abstract Background The optimal frequency of repeating blood cultures in persistent febrile neutropenia (FN) is unknown. We aim to characterize timing and microbiology of positive blood cultures in persistent FN to inform diagnostic stewardship of blood cultures at our cancer center. Flow diagram outlining methods for selecting patients to include in the study. Among qualifying FN episodes, only the first FN episode per patient was included in the analysis. Abbreviation: FN (febrile neutropenia). Methods This is a retrospective cohort study of adult hematology/oncology patients with a FN episode lasting > 3 days between March 31, 2021 - August 31, 2023. A day of FN was defined as a day with a patient temperature of ≥ 38C and an absolute neutrophil count ≤ 500 cells/µL within 24 hours of the qualifying temperature. Day 1 of FN was the first day a patient met FN criteria; the end of the FN episode was the last day of FN that was followed by ≥ 2 consecutive days where the patient no longer met FN criteria. All blood cultures collected during each FN episode were extracted from the medical record. Results Among 459 patients included (Figure 1), 420 (91%) had a hematologic malignancy (Table 1). The median FN duration was 5 days (interquartile range (IQR) 4-7). A median of 12 blood culture bottles were collected per patient during FN (IQR 8-18). At least 1 positive blood culture at any time during the FN episode occurred in 126 (27%) patients; 23 (5%) patients had ≥ 1 positive blood culture after FN day 3. For 12 of these 23 patients the positive blood culture(s) that occurred after FN day 3 were the first positive cultures during the FN episode. The percent of patients with ≥ 1 positive blood culture declined from 25% on FN day 1 to < 10% on FN days 2-4 and < 5% on FN days 5-8 (Figure 2). Among the 23 patients with positive blood cultures after FN day 3, gram positive bacteria were observed most frequently after FN day 3 (12 patients), with coagulase negative Staphylococci occurring most often. Gram negative bacteria and yeast were isolated in blood cultures after FN day 3 from 8 and 5 patients, respectively (Table 2). Bar chart depicting the number of patients on each day of FN who had at least one positive blood culture, no positive blood cultures, and no blood cultures collected. The table below the bar chart shows the total number of patients who met criteria for FN on each FN day, the number of those patients with at least one positive blood culture on a given FN day, and the percent of patients on each FN day who had at least one positive blood culture (among the patients who had at least one blood culture collected on the given FN day). Percentages were only calculated for days where there were ≥ 30 patients who had at least one blood culture collected (FN days 1-8). Abbreviation: FN (febrile neutropenia). Conclusion Few patients had a positive blood culture beyond day 3 of FN. Gram positive organisms, particularly coagulase negative Staphylococci, were most often isolated, raising the possibility that some of these late positive cultures may be skin contaminants rather than true bloodstream infections (BSI). Additional studies are needed to determine optimal frequency of blood culturing in persistent FN and to identify patients at high risk of late onset BSI. Disclosures Frank Tverdek, PharmD, Merck: Advisor/Consultant Catherine Liu, MD, Pfizer: Grant/Research Support
Abstract Background Rural and critical access hospitals (CAHs) serve 20% of the United States population. Fewer than 10% of US physicians practice in rural areas and workforce shortages and staff turnover are a constant threat. The University of Washington Center for Stewardship in Medicine (UW CSiM) supports a tele-antimicrobial stewardship (AMS) program (UW TASP ECHO) in small, rural, and CAHs, primarily in the western U.S. with education, mentoring, organizational capacity building, and a community of peers. Methods UW CSiM distributes an annual program evaluation survey to participating hospitals. In 2022, 2 questions were added to the survey and measured with a Likert scale from 1 (strongly disagree) to 5 (strongly agree): 1) Participation in UW-TASP increased my job satisfaction; 2). Participation has increased the likelihood that I will continue working in my institution. Respondents had the option to add free-text comments. Results were summarized descriptively. Results In 2023, 53/80 (66%) of hospitals responded, 44 (83%) met the definition of CAH. Response rate was 60% in 2022. In 2022 and 2023, 85% and 83% agreed or strongly agreed that participation in UW-TASP increased their job satisfaction. Seventy three percent (2022) and 64% (2023) agreed or strongly agreed that participating in UW-TASP increased the likelihood of continuing to work with their current institution. Comments included: “It's easy to feel "alone" out here in a rural area. Having TASP makes me feel very much a part of a community that I can share my barriers/struggles with and get ideas for how I can do more with my program.” “Knowledge is power, TASP provides knowledge to make us effective leaders and give the best patient care. That is what gives me job satisfaction, knowing I am helping patients with best practice.” Conclusion UW-TASP’s impact expands beyond checking a box that mandates AMS in every acute care hospital. We found establishing and maintaining a relationship with participants allowed us to build a community with and among rural and critical access hospital partners. This study is limited by self-reported survey data but demonstrates that engagement within UW-TASP is associated with increased job satisfaction and rural healthcare worker retention. Further qualitative studies are needed to further explore this. Disclosures All Authors: No reported disclosures
