Regulatory T cells (Treg) are immunosuppressive and negatively impact response to cancer immunotherapies. CREB-binding protein (CBP) and p300 are closely related acetyltransferases and ...transcriptional coactivators. Here, we evaluate the mechanisms by which CBP/p300 regulate Treg differentiation and the consequences of
loss-of-function mutations in follicular lymphoma. Transcriptional and epigenetic profiling identified a cascade of transcription factors essential for Treg differentiation. Mass spectrometry analysis showed that CBP/p300 acetylates prostacyclin synthase, which regulates Treg differentiation by altering proinflammatory cytokine secretion by T and B cells. Reduced Treg presence in tissues harboring
loss-of-function mutations was observed in follicular lymphoma. Our findings provide novel insights into the regulation of Treg differentiation by CBP/p300, with potential clinical implications on alteration of the immune landscape. SIGNIFICANCE: This study provides insights into the dynamic role of CBP/p300 in the differentiation of Tregs, with potential clinical implications in the alteration of the immune landscape in follicular lymphoma.
Medical students interested in neurosurgery are increasingly involved in research, and research conferences have proven valuable for developing medical research experience and exposure. A research ...conference was designed for medical students interested in neurosurgery to present research.
Our team designed an annual research conference at the Warren Alpert Medical School of Brown University in conjunction with the Neurosurgery and Neurology Departments. In February 2019, we hosted the first Student Neurosurgical and Neurological Research Conference (SNRC), the first national research conference, to our knowledge, designed for medical students to present neurosurgical research in the United States. The conference consisted of student poster/oral presentations, keynote speeches from clinical faculty, and surgical skills workstations. In February 2020, we hosted the second SNRC. After each conference, participants (n = 55) completed a survey to assess student perspectives of the conference.
Fifty-five medical students from around the nation attended the conferences to present their research. One hundred percent of participants affirmed that the conference fulfilled their primary reason for attending, which for most (54.5%) was the opportunity to present research. Thematic analysis revealed that students especially appreciated the “lower stress environment” and “opportunity to get feedback on their research.” Notably, 97.6% of students felt the conference strengthened or increased their interest in neurosurgery.
Participants felt that the SNRC was a valuable opportunity to present research in an environment conducive for practice and improvement. Research conferences primarily for medical students may support the development of young researchers while increasing and strengthening interest in the field of neurosurgery.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A need exists to better understand the prognostic factors that influence high-value care outcomes after meningioma surgery. The goal of the present study was to develop predictive models to determine ...the patients at risk of experiencing an extended hospital length of stay (LOS), nonroutine discharge disposition, and/or a 90-day hospital readmission after non–skull base meningioma resection.
In the present study, we analyzed the data from 396 patients who had undergone surgical resection of non–skull base meningiomas at a single institution between January 1, 2005 and December 31, 2020. The Mann-Whitney U test was used for bivariate analysis of the continuous variables and the Fisher exact test for bivariate analysis of the categorical variables. A multivariate analysis was conducted using logistic regression models.
Most patients had had a falcine or parasagittal meningioma (66.2%), with the remainder having convexity (31.8%) or intraventricular (2.0%) tumors. Nonelective surgery (P < 0.0001) and an increased tumor volume (P = 0.0022) were significantly associated with a LOS >4 days on multivariate analysis. The independent predictors of a nonroutine discharge disposition included male sex (P = 0.0090), nonmarried status (P = 0.024), nonelective surgery (P = 0.0067), tumor location within the parasagittal or intraventricular region (P = 0.0084), and an increased modified frailty index score (P = 0.039). Hospital readmission within 90 days was independently associated with nonprivate insurance (P = 0.010) and nonmarried status (P = 0.0081). Three models predicting for a prolonged LOS, nonroutine discharge disposition, and 90-day readmission were implemented in the form of an open-access, online calculator (available at: https://neurooncsurgery3.shinyapps.io/non_skull_base_meningiomas/).
After external validation, our open-access, online calculator could be useful for assessing the likelihood of adverse postoperative outcomes for patients undergoing surgery of non–skull base meningioma.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Playing musical instruments is not associated with general surgery technical skills.•Participation in sports and hobbies requiring hand-eye coordination are not associated with general surgery ...technical skills.•Hobbies prior to residency are not likely to predict future technical skills as a general surgery resident.
To determine whether participation in certain hobbies (e.g., participation in sports, playing musical instruments, or other hobbies requiring fine motor skills), preresidency, are associated with higher technical skills ratings at the time of residency graduation.
Faculty members from 14 general surgery residency programs scored individual graduates from 2017 to 2020 on their technical skills using a 5-point Likert scale. Hobbies for these residents were collected from their Electronic Residency Application Service (ERAS) data. A single reviewer classified each ERAS hobby into predefined categories including musical instruments, sports requiring hand-eye coordination, team sports, and activities necessitating hand-eye coordination. Spearman correlation coefficients were calculated for the relationship between each category of hobby—as well as the total number of hobbies in each category—and the outcome of surgical faculty ratings of residents’ technical surgical skills during their last year of residency. A proportional odds model including the above predictive variables was also fit to the data.
Fourteen general surgery residency programs.
General surgery residency graduates from 14 different programs from 2017 to 2020.
There were 296 residents across 14 institutions. The average ranking of residents’ technical skills was 3.24 (SD 1.1). A total of 40% of residents played sports involving hand-eye coordination, 31% played team sports, 28% participated in nonsport hobbies that require eye-hand coordination, and 20% played musical instruments. Correlation coefficients were not statistically significant for any of the categories. In the proportional odds model, none of the variables were associated with statistically significant increased odds of a higher technical skills rating.
There was no correlation between general surgery chief residents’ technical skills as rated by faculty, and self-reported pre-residency hobbies on the ERAS application. These findings suggest such hobbies prior to residency are unlikely to predict future technical skills prowess.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
The safety and efficacy of anticoagulation in managing superior sagittal sinus (SSS) thrombosis remains unclear. The present study investigated the relationship between anticoagulation and ...cerebrovascular complications in parasagittal/parafalcine meningioma patients presenting with post-surgical SSS thrombosis.
Methods
We analyzed 266 patients treated at a single institution between 2005 and 2020. Bivariate analysis was conducted using the Mann–Whitney U test and Fisher’s exact test. Multivariate analysis was conducted using a logistic regression model. Blood thinning medications investigated included aspirin, warfarin, heparin, apixaban, rivaroxaban, and other novel oral anticoagulants (NOACs). A symptomatic SSS thrombosis was defined as a radiographically apparent thrombosis with new headaches, seizures, altered sensorium, or neurological deficits.
Results
Our patient cohort was majority female (67.3%) with a mean age (
±
SD) of 58.82
±
13.04 years. A total of 15 (5.6%) patients developed postoperative SSS thrombosis and 5 (1.9%) were symptomatic; 2 (0.8%) symptomatic patients received anticoagulation. None of these 15 patients developed cerebrovascular complications following observation or anticoagulative treatment of asymptomatic SSS thrombosis. While incidence of any other postoperative complications was significantly associated with SSS thrombosis in bivariate analysis (p = 0.015), this association was no longer observed in multivariate analysis (OR = 2.15, p = 0.16) when controlling for patient age, sex, and anatomical location of the tumor along the SSS.
Conclusions
Our single-institution study examining the incidence of SSS thrombosis and associated risk factors highlights the need for further research efforts better prognosticate this adverse outcome. Conservative management may represent a viable treatment strategy for patients with SSS thrombosis.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Casual social touch influences emotional perceptions, attitudes, and behaviours of interaction partners. We asked whether these influences extend to third‐party observers. To this end, we developed ...the Social Touch Picture Set comprising line drawings of dyadic interactions, half of which entailed publicly acceptable casual touch and half of which served as no‐touch controls. In Experiment 1, participants provided basic image norms by rating how frequently they observed a displayed touch gesture in everyday life and how comfortable they were observing it. Results implied that some touch gestures were observed more frequently and with greater comfort than others (e.g., handshake vs. hug). All gestures, however, obtained rating scores suitable for inclusion in Experiments 2 and 3. In Experiment 2, participants rated perceived valence, arousal, and likeability of randomly presented touch and no‐touch images without being explicitly informed about touch. Image characters seemed more positive, aroused, and likeable when they touched as compared to when they did not touch. Image characters seemed more negative and aroused, but were equally likeable, when they received touch as compared to when there was no physical contact. In Experiment 3, participants passively viewed touch and no‐touch images while their eye movements were recorded. Differential gazing at touch as compared to no‐touch images emerged within the first 500 ms following image exposure and was largely restricted to the characters' upper body. Gazing at the touching body parts (e.g., hands) was minimal and largely unaffected by touch, suggesting that touch processing occurred outside the focus of visual attention. Together, these findings establish touch as an important visual cue and provide novel insights into how this cue modulates socio‐emotional processing in third‐party observers.
Full text
Available for:
BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Pneumatosis intestinalis (PI) is associated with numerous adult conditions, ranging from benign to life threatening. To date, series of PI outcomes consist of case reports and small retrospective ...series.
We conducted a retrospective multicenter study, involving eight centers, of PI from January 2001 to December 2010. Demographics, medical history, clinical presentation, and outcomes were collected. Primary outcome was the presence of pathologic PI defined as confirmed transmural ischemia at surgery or the withdrawal of clinical care and subsequent mortality. Forward logistic regression and a regression tree analysis was used to generate a clinical prediction rule for pathologic PI.
During the 10-year study period, 500 patients with PI were identified. Of this number, 299 (60%) had benign disease, and 201 (40%) had pathologic PI. A wide variety of variables were statistically significant predictors of pathologic PI on univariate comparison. In the regression model, a lactate of 2.0 or greater was the strongest independent predictor of pathologic PI, with hypotension or vasopressor need, peritonitis, acute renal failure, active mechanical ventilation, and absent bowel sounds also demonstrating significance. Classification and regression tree analysis was used to create a clinical prediction rule. In this tree, the presence of a lactate value of 2.0 or greater and hypotension/vasopressor use had a predictive probability of 93.2%.
Discerning the clinical significance of PI remains a challenge. We identified the independent predictors of pathologic PI in the largest population to date and developed of a basic predictive model for clinical use. Prospective validation is warranted.
Epidemiologic study, level III.
The goal of this study was to determine insulin sensitivity in a fasted state and during an oral glucose tolerance test (OGTT), in normoglycemic (NGT), lean (L) (n = 35) and, for comparison, ...overweight/obese (OW/O) (n = 9) college-aged subjects.
Insulin sensitivity for 44 NGT, normotensive subjects, age 18–26 yrs., was determined by homeostasis model assessment (HOMA-IR) and from Matsuda index (ISI Matsuda).
Subjects were normoglycemic fasted (4.59 + 0.35 mmol/L) and at two hours post OGTT (4.52 + 1.35 mmol/L). Besides anthropometric measures, there were significant differences between OW/O and L for fasting insulin (P < 0.001) and both measures of insulin sensitivity (P < 0.05). All subjects exhibited a 9-fold range in HOMA-IR (0.88 + 0.51, range 0.3–2.7) and an 8-fold range in ISI Matsuda (11.9 + 4.7, range 3.0–24.2). The latter was inversely correlated with systolic blood pressure (r = 0.35, P = 0.04) even though subjects were normotensive. In lean subjects, 2.3% were IR by HOMA-IR > 2.1, 5.7% by ISI Matsuda < 5.9, and 22.9% had >one criteria for metabolic syndrome (MetS); 28.6% had some negative metabolic biomarker.
Insulin resistance is present in lean, NGT college-age subjects even without MetS criteria and is discernable with an easily applicable OGTT-derived index.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
PDF
