Racial and Ethnic Disparities in the Incidence of Anti-NMDA Receptor Encephalitis.

OBJECTIVES: To estimate the incidence of anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis. METHODS: We conducted a retrospective cohort study of >10 million person-years of observation from members of Kaiser Permanente Southern California, 2011-2022. The electronic health record of individuals with text-string mention of NMDA and encephalitis were reviewed to identify persons who met diagnostic criteria for anti-NMDAR encephalitis. Age-standardized and sex-standardized incidences stratified by race and ethnicity were estimated according to the 2020 US Census population. RESULTS: We identified 70 patients who met diagnostic criteria for anti-NMDAR encephalitis. The median age at onset was 23.7 years (IQR = 14.2-31.0 years), and 45 (64%) were female patients. The age-standardized and sex-standardized incidence of anti-NMDAR encephalitis per 1 million person-years was significantly higher in Black (2.94, 95% CI 1.27-4.61), Hispanic (2.17, 95% CI 1.51-2.83), and Asian/Pacific Island persons (2.02, 95% CI 0.77-3.28) compared with White persons (0.40, 95% CI 0.08-0.72). Ovarian teratomas were found in 58.3% of Black female individuals and 10%-28.6% in other groups. DISCUSSION: Anti-NMDA receptor encephalitis disproportionately affected Black, Hispanic, or Asian/Pacific Island persons. Ovarian teratomas were a particularly common trigger in Black female individuals. Future research should seek to identify environmental and biological risk factors that disproportionately affect minoritized individuals residing in the United States.

Hysteroscopy needs of indigenous communities in Northern Quebec: a retrospective cohort study.

We aimed to determine the surgical output for patients from Nunavik undergoing transfer to an urban centre for hysteroscopy, and associated costs. We performed a retrospective chart review of all patients from the 14 villages of Nunavik transferred for hysteroscopic surgery from 2016 to 2021. Diagnoses, surgical intervention, and nature of the procedure were all extracted from the patient charts, and costs/length of stay obtained from logisticians and administrators servicing the Nunavik region. Over a 5-year period, 22 patients were transferred from Nunavik for hysteroscopy, of which all were elective save one. The most common diagnosis was endometrial or cervical polyp and the most common procedure was diagnostic hysteroscopy. The average cost for patient transfer and lodging to undergo hysteroscopy in Montreal ranged from $6,000 to $15,000 CDN. On average, 4-5 patient transfers occur annually for hysteroscopy, most commonly for management of endometrial polyps, at a cost of $6,000 to $15,000 CDN, suggesting the need to investigate local capacity building in Nunavik and assess cost-effectiveness.

Mast cell distribution and prevalence in the murine urinary bladder.

BACKGROUND: Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains uncertain despite mast cell prevalence being relatively well-defined. Using a mouse tissue model, this study aims to characterise the prevalence and distribution of mast cells throughout the urinary bladder. METHODS: Bladder tissues were collected from six C57BL/6J female mice. Mast cell prevalence was quantified by flow cytometry, based on the expression of the following characteristic markers: CD45, CD117 and FcɛRIα. The toluidine blue stain assessed mast cell distribution, size, and proximity to vasculature. A repeated measures one-way ANOVA was used to evaluate the density of mast cells between the discrete layers of the urinary bladder, and an ordinary one-way ANOVA was used to assess potential differences between mast cell size across the urinary bladder wall. RESULTS: It was determined that mast cells compose less than 4% of all live leukocytes in the urinary bladder. They were also found to be more prominent in the lamina propria and detrusor muscle layers, compared to the urothelium and adventitia. In addition, 20.89% of mast cells were located near vasculature, which may be an important factor in consideration of their function and potential to contribute to various bladder pathologies, such as cystitis or overactive bladder. CONCLUSION: These findings provide a baseline understanding of mast cell prevalence and distribution throughout the urinary bladder.

The effect of myeloablative radiation on urinary bladder mast cells.

Radiation-induced cystitis is an inflammatory condition affecting the urinary bladder, which can develop as a side effect of abdominopelvic radiotherapy, specifically external-beam radiation therapy or myeloablative radiotherapy. A possible involvement of mast cells in the pathophysiology of radiation-induced cystitis has been indicated in cases of external-beam radiation therapy; however, there is no evidence that these findings apply to the myeloablative aetiology. As such, this study investigated potential changes to urinary bladder mast cell prevalence when exposed to myeloablative radiation. Lethally irradiated C57BL/6J mice that received donor rescue bone marrow cells exhibited an increased mast cell frequency amongst host leukocytes 1 week following irradiation. By 4 weeks, no significant difference in either frequency or cell density was observed. However mast cell diameter was smaller, and a significant increase in mast cell number in the adventitia was observed. This study highlights that mast cells constitute a significant portion of the remaining host leukocyte population following radiation exposure, with changes to mast cell distribution and decreased cell diameter four weeks following radiation-induced injury.

Update on ischemic hepatitis.

PURPOSE OF REVIEW: Ischemic hepatitis (IH) refers to diffuse liver injury secondary to hypoperfusion. The condition is usually seen in the critical care setting and is associated with significant mortality. IH typically occurs in the setting of systemic hypotension superimposed on some form of underlying cardiac dysfunction. This review aims to report what is known and what is new about the etiology, pathophysiology, and clinical features associated with IH. RECENT FINDINGS: In recent years, studies on IH have largely confirmed earlier reports regarding etiologies, comorbid conditions, and associated mortality. Recent study has also shed light on the potential treatment of IH with N -acetyl-cysteine (NAC). SUMMARY: IH is typically associated with underlying cardiac disease, and patients with IH have a very high mortality rate. Treatment remains largely supportive, although the utility of agents such as NAC are being explored.

Reconstructing curcumin biosynthesis in yeast reveals the implication of caffeoyl-shikimate esterase in phenylpropanoid metabolic flux.

Curcumin is a polyphenolic natural product from the roots of turmeric (Curcuma longa). It has been a popular coloring and flavoring agent in food industries with known health benefits. The conventional phenylpropanoid pathway is known to proceed from phenylalanine via p-coumaroyl-CoA intermediate. Although hydroxycinnamoyl-CoA: shikimate hydroxycinnamoyl transferase (HCT) plays a key catalysis in the biosynthesis of phenylpropanoid products at the downstream of p-coumaric acid, a recent discovery of caffeoyl-shikimate esterase (CSE) showed that an alternative pathway exists. Here, the biosynthetic efficiency of the conventional and the alternative pathway in producing feruloyl-CoA was examined using curcumin production in yeast. A novel modular multiplex genome-edit (MMG)-CRISPR platform was developed to facilitate rapid integrations of up to eight genes into the yeast genome in two steps. Using this MMG-CRISPR platform and metabolic engineering strategies, the alternative CSE phenylpropanoid pathway consistently showed higher titers (2-19 folds) of curcumin production than the conventional pathway in engineered yeast strains. In shake flask cultures using a synthetic minimal medium without phenylalanine, the curcumin production titer reached up to 1.5 mg/L, which is three orders of magnitude (∼4800-fold) improvement over non-engineered base strain. This is the first demonstration of de novo curcumin biosynthesis in yeast. Our work shows the critical role of CSE in improving the metabolic flux in yeast towards the phenylpropanoid biosynthetic pathway. In addition, we showcased the convenience and reliability of modular multiplex CRISPR/Cas9 genome editing in constructing complex synthetic pathways in yeast.

Medical Management of Ovarian Endometriomas: A Systematic Review and Meta-analysis.

OBJECTIVE: To estimate the effect of medical management on the size of ovarian endometriomas. DATA SOURCE: Online databases were searched from inception to October 2022, including Ovid MEDLINE, Ovid EMBASE, PubMed, EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science. METHODS OF STUDY SELECTION: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we included all English-language, full-text articles that reported on change in endometrioma size (either diameter or volume) after medical interventions. Studies evaluating surgical interventions or postoperative recurrence were excluded. All screening and data extraction were performed independently by two authors. Risk of bias assessment was performed with either the Cochrane Risk of Bias Tool for randomized controlled trials or a modified Newcastle-Ottawa Scale for observational studies. TABULATION, INTEGRATION, AND RESULTS: After removal of duplicates, 9,332 studies were screened, with 33 full-text articles deemed eligible for inclusion. In the meta-analysis, dienogest showed significant reduction in cyst diameter (reduction 1.32 cm, 95% CI, 0.91-1.73, eight studies, n=418 cysts) and volume (mean difference of log-transformed volume 1.35, 95% CI, 0.87-1.83, seven studies, n=282 cysts). Similarly, significant reductions were seen with the oral contraceptive pill (OCP) (1.06 cm, 95% CI, 0.59-1.53, nine studies, n=455), gonadotropin-releasing hormone (GnRH) agonists (1.17 cm, 95% CI, 0.42-1.92, four studies, n=128 cysts), norethindrone acetate (0.6 cm, 95% CI, 0.27-0.94, two studies, n=88 cysts), and danazol (1.95 cm, 95% CI, 1.18-2.73, two studies, n=34 cysts). Norethindrone acetate with aromatase inhibitor was also effective in reducing endometrioma volume (mean difference of log-transformed volume 1.47, 95% CI, 0.16-2.78, two studies, n=34 cysts). CONCLUSION: Medical management with dienogest, OCPs, GnRH agonists, norethindrone acetate, norethindrone acetate with aromatase inhibitor, or danazol can reduce the size of ovarian endometriomas. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD 42022363319.

Health risks associated with smoking versus injecting fentanyl among people who use drugs in California.

BACKGROUND: Given the attention, funding, and services that seek to reduce overdose mortality from fentanyl, it is important to understand whether a potential solution is for more people to switch from injecting to smoking fentanyl. As such, we set out to conduct a study to compare health and healthcare utilization outcomes associated with different modes of illicit fentanyl administration. METHODS: From January to February 2023, we recruited people who use drugs from 34 syringe services programs across California, USA (N=999) and surveyed their substance use, health outcomes, and healthcare utilization. We compared health risks among people who injected fentanyl (78% of whom also smoked) to people who solely smoked fentanyl (n=563). RESULTS: Of the 563 participants, forty-one percent injected fentanyl and 59% only smoked fentanyl. People who injected fentanyl were 40% more likely to have experienced a non-fatal overdose in the past 3 months (27% vs. 19%; aRR=1.40; 95% CI=1.03, 1.93) and 253% more likely to have had a skin and soft tissue infection in the past 3 months (39% vs. 15%; aRR=2.53; 95% CI=1.74, 3.67), compared to people who only smoked fentanyl. The average number of nights spent in the hospital was higher among people who injected fentanyl (average 1.2 nights vs. 0.7 nights; aIRR=1.78; 95% CI=1.02, 3.09; p=0.04).There were non-significant associations between mode of fentanyl administration and number of emergency department visits and probability of hospitalization. CONCLUSIONS: Findings suggested that people who injected fentanyl were at higher risk for overdose and skin and soft tissue infections than people who only smoked fentanyl. Distribution of safe smoking supplies may facilitate transitions from injecting to smoking fentanyl, thereby reducing health risks associated with fentanyl use.

Interests and Barriers to Medical Students Participation in a Dedicated Global Surgery Curriculum.

INTRODUCTION: Despite many institutions establishing global surgery (GS) programs to support clinical care and education in resource-limited settings, few have established a specific curriculum in GS. This study's objective was to assess medical student interest in such a curriculum and prospects for future careers in GS/global health (GH), and to define the barriers to pursuing an international rotation. METHODS: We conducted an anonymous online survey of all 495 medical students at a major academic medical center in the mid-South that collected demographic data, country of origin, interest in a GS/GH elective, and barriers to pursuing a GS/GH rotation abroad. The data were analyzed using SPSS software. RESULTS: Prior international experience increased the likelihood of a student's involvement in GS/GH and more preclinical (years 1 & 2) students (90%) than clinical students. (years 3 & 4) (70%) felt strongly about the value of a GS/GH experience. Of the 163 students who completed the survey, 80% expressed interest in a GS/GH elective, with preclinical students expressing more interest (90%) than clinical students (71%). This interest strongly correlated with an interest in pursuing a career in GH (94%) and/or GS (100%). Identified barriers to engagement in a GS/GH experience abroad included financing (74%), scheduling (58%), family obligations (23%), and personal safety (19%). CONCLUSIONS: The students we surveyed were very interested in a GS/GH curriculum that included a rotation abroad, especially if they were to receive financial support. Preclinical students expressed more willingness to self-fund such experiences. The findings of this survey further strengthen the need to incorporate GS/GH in medical school curricula.

The effects of radiation on myeloid lineage immune cells within the rodent urinary bladder: a systematic review.

PURPOSE: Radiotherapy is a prominent therapy for many malignant and non-malignant disorders, though it can cause side effects such as radiation-induced cystitis. Current research has highlighted a role for mast cells and macrophages in the prognosis of such radiation-induced toxicities. However, the prognostic value of these immune cells in the pathophysiology of radiation-induced cystitis is not clear. As such, a systematic review was conducted to assess myeloid-lineage immune cells for their prognostic value in radiation-induced cystitis to address this gap in literature. METHODS: The protocol was registered in PROSPERO, and searches were performed in PubMed, Embase and Web of Science databases for pre-clinical rodent studies on radiation-induced cystitis. RESULTS: After de-duplication, 153 articles were screened for relevancy by title and abstract. Title and abstract screening deemed 64 studies irrelevant. The remaining 85 studies were full-text screened, yielding seven unique articles for data extraction. Most included studies had an unclear risk of bias. The findings of this systematic review suggest that the prognostic value of myeloid-lineage immune cells in radiation-induced cystitis is still unclear, indicating a need for further research in this field. CONCLUSION: Although the studies reviewed provide some insight into the role of these immune cells in disease pathology, the limited number of studies and unclear risk of bias further highlights a need for additional, high-quality research in this area. In summary, this systematic review highlights a need to understand the involvement of immune cells in radiation-induced cystitis pathophysiology and lay the groundwork for further research in this area. TRIAL REGISTRATION: PROSPERO registration: CRD42022345960.

Guideline No. 437: Diagnosis and Management of Adenomyosis.

OBJECTIVE: To describe the current evidence-based diagnosis and management of adenomyosis. TARGET POPULATION: All patients with a uterus of reproductive age. OPTIONS: Diagnostic options include transvaginal sonography and magnetic resonance imaging. Treatment options should be tailored to symptoms (heavy menstrual bleeding, pain, and/or infertility) and include medical options (non-steroidal anti-inflammatory drugs, tranexamic acid, combined oral contraceptives, levonorgestrel intrauterine system, dienogest, other progestins, gonadotropin-releasing analogues), interventional options (uterine artery embolization), and surgical options (endometrial ablation, excision of adenomyosis, hysterectomy). OUTCOMES: Outcomes of interest include reduction in heavy menstrual bleeding, reduction in pelvic pain (dysmenorrhea, dyspareunia, chronic pelvic pain), and improvement in reproductive outcomes (fertility, miscarriage, adverse pregnancy outcomes). BENEFITS, HARMS, AND COSTS: This guideline will benefit patients with gynaecological complaints that may be caused by adenomyosis, especially those patients who wish to preserve their fertility, by presenting diagnostic methods and management options. It will also benefit practitioners by improving their knowledge of various options. EVIDENCE: Databases searched were MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed, EMBASE. The initial search was completed in 2021 and updated with relevant articles in 2022. Search terms included adenomyosis, adenomyoses, endometritis (used/indexed as adenomyosis before 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis] AND [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Articles included randomized controlled trials, meta-analyses, systematic reviews, observational studies, and case reports. Articles in all languages were searched and reviewed. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetrician-gynaecologists, radiologists, family physicians, emergency physicians, midwives, registered nurses, nurse practitioners, medical students, residents, and fellows. TWEETABLE ABSTRACT: Adenomyosis is common in reproductive-aged women. There are diagnostic and management options that preserve fertility available. SUMMARY STATEMENTS: RECOMMENDATIONS.

Directive clinique no 437 : Diagnostic et prise en charge de l'adénomyose.

OBJECTIF: Décrire les pratiques actuelles fondées sur des données probantes pour le diagnostic et la prise en charge de l'adénomyose. POPULATION CIBLE: Toutes les patientes en âge de procréer qui ont un utérus. OPTIONS: Les options diagnostiques sont l'échographie endovaginale et l'imagerie par résonance magnétique. Les options thérapeutiques doivent être adaptées aux symptômes (saignements menstruels abondants, douleur et/ou infertilité) et comprendre des options médicamenteuses (anti-inflammatoires non stéroïdiens, acide tranexamique, contraceptifs oraux combinés, système intra-utérin à libération de lévonorgestrel, diénogest, autres progestatifs, analogues de la gonadotrophine), des options interventionnelles (embolisation de l'artère utérine) et des options chirurgicales (ablation de l'endomètre, excision de l'adénomyose, hystérectomie). RéSULTATS: Les critères de jugement sont la réduction des saignements menstruels abondants, l'atténuation de la douleur pelvienne (dysménorrhée, dyspareunie, douleur pelvienne chronique) et l'amélioration du devenir reproductif (fertilité, avortement spontané, issues de grossesse défavorables). BéNéFICES, RISQUES ET COûTS: Par la présentation des méthodes de diagnostic et des options de prise en charge, cette directive sera bénéfique pour les patientes qui expriment des plaintes de nature gynécologique potentiellement causées par l'adénomyose, en particulier celles qui souhaitent préserver leur fertilité. La directive sera également utile aux praticiens qui pourront améliorer leurs connaissances sur les différentes options. DONNéES PROBANTES: Des recherches ont été effectuées dans les bases de données MEDLINE Reviews, MEDLINE ALL, Cochrane, PubMed et Embase. La recherche initiale a été réalisée en 2021 et mise à jour avec les articles pertinents en 2022. Les termes de recherche utilisés sont les suivants : adenomyosis, adenomyoses, endometritis (utilisés ou indexés sous adenomyosis avant 2012), (endometrium AND myometrium) uterine adenomyosis/es, symptom/s/matic adenomyosis ET [diagnosis, symptoms, treatment, guideline, outcome, management, imaging, sonography, pathogenesis, fertility, infertility, therapy, histology, ultrasound, review, meta-analysis, evaluation]. Les articles retenus sont des essais cliniques randomisés, des méta-analyses, des revues systématiques, des études observationnelles et des études de cas. Des articles dans toutes les langues ont été répertoriés et examinés. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (Tableau A1 pour les définitions et Tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens-gynécologues, radiologistes, médecins de famille, urgentologues, sages-femmes, infirmières autorisées, infirmières praticiennes, étudiants en médecine, résidents et moniteurs cliniques (fellows). RéSUMé POUR TWITTER: L'adénomyose est fréquemment observée chez les femmes en âge de procréer. Il existe des options de diagnostic et de prise en charge qui préservent la fertilité. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Subtyping patients with chronic disease using longitudinal BMI patterns.

Obesity is a major health problem, increasing the risk of various major chronic diseases, such as diabetes, cancer, and stroke. While the role of obesity identified by cross-sectional BMI recordings has been heavily studied, the role of BMI trajectories is much less explored. In this study, we use a machine learning approach to subtype individuals' risk of developing 18 major chronic diseases by using their BMI trajectories extracted from a large and geographically diverse EHR dataset capturing the health status of around two million individuals for a period of six years. We define nine new interpretable and evidence-based variables based on the BMI trajectories to cluster the patients into subgroups using the k-means clustering method. We thoroughly review each cluster's characteristics in terms of demographic, socioeconomic, and physiological measurement variables to specify the distinct properties of the patients in the clusters. In our experiments, the direct relationship of obesity with diabetes, hypertension, Alzheimer's, and dementia has been re-established and distinct clusters with specific characteristics for several of the chronic diseases have been found to be conforming or complementary to the existing body of knowledge.

Pharmacologic Interventions to Minimize Fluid Absorption at the Time of Hysteroscopy: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess which interventions are effective in reducing fluid absorption at the time of hysteroscopy. DATA SOURCE: Ovid MEDLINE, Ovid EMBASE, PubMed (non-MEDLINE records only), EBM Reviews-Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science were searched from inception to February 2022 without restriction on language or geographic origin. METHODS OF STUDY SELECTION: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, all English-language, full-text articles reporting fluid balance, with an intervention and comparator arm, were included. Title and abstract screening and full-text review were completed independently by two authors. Conflicts were resolved through discussion and consensus. Studies' risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies. TABULATION, INTEGRATION, AND RESULTS: The search identified 906 studies, 28 of which were eligible for inclusion, examining the following interventions: gonadotropin-releasing hormone (GnRH) agonist; ulipristal acetate; vasopressin; danazol; oxytocin; and local, general, and regional anesthesia. A significant reduction in mean fluid absorption was seen in patients preoperatively treated with danazol (-175.7 mL, 95% CI -325.4 to -26.0) and a GnRH agonist (-139.68 mL, 95% CI -203.2, -76.2) compared with patients in a control group. Ulipristal acetate and type of anesthesia showed no difference. Data on type of anesthesia and vasopressin use were not amenable to meta-analysis; however, four studies favored vasopressin over control regarding fluid absorption. Mean operative time was reduced after preoperative treatment with ulipristal acetate (-7.1 min, 95% CI -11.31 to -2.9), danazol (-7.5 min, 95% CI -8.7 to -6.3), and a GnRH agonist (-3.3 min, 95% CI -5.6 to -0.98). CONCLUSION: Preoperative treatment with a GnRH agonist and danazol were both found to be effective in reducing fluid absorption and operative time across a range of hysteroscopic procedures. High-quality research aimed at evaluating other interventions, such as combined hormonal contraception, progestin therapy, and vasopressin, are still lacking in the literature. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021233804.

Natural history, angiographic presentation and outcomes of anterior cranial fossa dural arteriovenous fistulas.

BACKGROUND: Anterior cranial fossa dural arteriovenous fistulas (ACF-dAVFs) are aggressive vascular lesions. The pattern of venous drainage is the most important determinant of symptoms. Due to the absence of a venous sinus in the anterior cranial fossa, most ACF-dAVFs have some degree of drainage through small cortical veins. We describe the natural history, angiographic presentation and outcomes of the largest cohort of ACF-dAVFs. METHODS: The CONDOR consortium includes data from 12 international centers. Patients included in the study were diagnosed with an arteriovenous fistula between 1990-2017. ACF-dAVFs were selected from a cohort of 1077 arteriovenous fistulas. The presentation, angioarchitecture and treatment outcomes of ACF-dAVF were extracted and analyzed. RESULTS: 60 ACF-dAVFs were included in the analysis. Most ACF-dAVFs were symptomatic (38/60, 63%). The most common symptomatic presentation was intracranial hemorrhage (22/38, 57%). Most ACF-dAVFs drained through cortical veins (85%, 51/60), which in most instances drained into the superior sagittal sinus (63%, 32/51). The presence of cortical venous drainage predicted symptomatic presentation (OR 9.4, CI 1.98 to 69.1, p=0.01). Microsurgery was the most effective modality of treatment. 56% (19/34) of symptomatic patients who were treated had complete resolution of symptoms. Improvement of symptoms was not observed in untreated symptomatic ACF-dAVFs. CONCLUSION: Most ACF-dAVFs have a symptomatic presentation. Drainage through cortical veins is a key angiographic feature of ACF-dAVFs that accounts for their malignant course. Microsurgery is the most effective treatment. Due to the high risk of bleeding, closure of ACF-dAVFs is indicated regardless of presentation.

The impact of COVID-19 on medium term weight loss and comorbidities in patients undergoing bariatric surgery and its association with psychological wellbeing.

BACKGROUND: The COVID-19 epidemic imposed significant stressors on individuals and changed how medical care is delivered. The affect that this stress has placed on the field of bariatric surgery and the associated outcomes is not well established. METHODS: A retrospective review of a prospectively collected database from a single academic institution was conducted. Weight loss and comorbidity outcomes were compared between a cohort of patients operated on during the pandemic and a matched group operated on prior to COVID-19. GAD-7 and PHQ-9 questionnaires were used to assess for anxiety and depression, respectively. RESULTS: A total of 329 and 155 patients were enrolled in the pre-pandemic and COVID-19 groups respectively. There were no significant differences in pre-operative BMI (p = 0.437) or comorbidities: Type II DM (p = 0.810), hypertension (p = 0.879), sleep apnea (p = 0.502), and hyperlipidemia (p = 0.227). Post-operatively, weight loss was comparable at all time points out to 1 year. Type II DM resolution rates were higher in the control cohort at 6 months (p = 0.007), but not at 12 months (p = 1.000). There was no statistically significant difference in resolution rates between the control group and the COVID-19 group for the other measured comorbidities. There was no difference in objective measures of anxiety and depression when comparing the two groups (both p > 0.05). CONCLUSIONS: The COVID-19 pandemic has fundamentally changed how society and medical systems function. Focusing on pre-operative dietary training and screening for inadequately managed psychological comorbidities yielded similar weight loss outcomes notwithstanding the significant societal and individual stressors with which patients were faced.

Duration of Prophylactic Levetiracetam After Surgery for Brain Tumor: A Prospective Randomized Trial.

BACKGROUND: Levetiracetam is commonly used as a prophylactic antiseizure medication in patients undergoing surgical resection of brain tumors. OBJECTIVE: To quantitate side effects experienced in patients treated with 1 week vs 6 weeks of prophylactic levetiracetam using validated measures for neurotoxicity and depression. METHODS: Patients undergoing surgical resection of a supratentorial tumor with no seizure history were randomized within 48 hours of surgery to receive prophylactic levetiracetam for the duration of either 1 or 6 weeks. Patients were given oral levetiracetam extended release 1000 mg during the first part of this study. Owing to drug backorder, patients enrolled later in this study received levetiracetam 500 mg BID. The primary outcome was the change in the neurotoxicity score 6 weeks after drug initiation. The secondary outcome was seizure incidence. RESULTS: A total of 81 patients were enrolled and randomized to 1 week (40 patients) or 6 weeks (41 patients) of prophylactic levetiracetam treatment. The neurotoxicity score slightly improved in the overall cohort between baseline and reassessment. There was no significant difference between groups in neurotoxicity or depression scores. Seizure incidence was low in the entire cohort of patients with 1 patient in each arm experiencing a seizure during the follow-up period. CONCLUSION: The use of prophylactic levetiracetam did not result in significant neurotoxicity or depression when given for either 1 week or 6 weeks. The incidence of seizure after craniotomy for tumor resection is low regardless of duration of therapy.

Discovery of small molecule inhibitors that effectively disrupt IQGAP1-Cdc42 interaction in breast cancer cells.

The small GTPase Cdc42 is an integral component of the cytoskeleton, and its dysregulation leads to pathophysiological conditions, such as cancer. Binding of Cdc42 to the scaffold protein IQGAP1 stabilizes Cdc42 in its active form. The interaction between Cdc42 and IQGAP1 enhances migration and invasion of cancer cells. Disrupting this association could impair neoplastic progression and metastasis; however, no effective means to achieve this has been described. Here, we screened 78,500 compounds using a homogeneous time resolved fluorescence-based assay to identify small molecules that disrupt the binding of Cdc42 to IQGAP1. From the combined results of the validation assay and counter-screens, we selected 44 potent compounds for cell-based experiments. Immunoprecipitation and cell viability analysis rendered four lead compounds, namely NCGC00131308, NCGC00098561, MLS000332963 and NCGC00138812, three of which inhibited proliferation and migration of breast carcinoma cells. Microscale thermophoresis revealed that two compounds bind directly to Cdc42. One compound reduced the amount of active Cdc42 in cells and effectively impaired filopodia formation. Docking analysis provided plausible models of the compounds binding to the hydrophobic pocket adjacent to the GTP binding site of Cdc42. In conclusion, we identified small molecules that inhibit binding between Cdc42 and IQGAP1, which could potentially yield chemotherapeutic agents.