Intraoperative Hypotension in Patients Having Major Noncardiac Surgery Under General Anesthesia: A Systematic Review of Blood Pressure Optimization Strategies.

INTRODUCTION: Intraoperative hypotension is associated with increased risks of postoperative complications. Consequently, a variety of blood pressure optimization strategies have been tested to prevent or promptly treat intraoperative hypotension. We performed a systematic review to summarize randomized controlled trials that evaluated the efficacy of blood pressure optimization interventions in either mitigating exposure to intraoperative hypotension or reducing risks of postoperative complications. METHODS: Medline, Embase, PubMed, and Cochrane Controlled Register of Trials were searched from database inception to August 2, 2023, for randomized controlled trials (without language restriction) that evaluated the impact of any blood pressure optimization intervention on intraoperative hypotension and/or postoperative outcomes. RESULTS: The review included 48 studies (N = 46,377), which evaluated 10 classes of blood pressure optimization interventions. Commonly assessed interventions included hemodynamic protocols using arterial waveform analysis, preoperative withholding of antihypertensive medications, continuous blood pressure monitoring, and adjuvant agents (vasopressors, anticholinergics, anticonvulsants). These same interventions reduced intraoperative exposure to hypotension. Conversely, low blood pressure alarms had an inconsistent impact on exposure to hypotension. Aside from limited evidence that higher prespecified intraoperative blood pressure targets led to a reduced risk of complications, there were few data suggesting that these interventions prevented postoperative complications. Heterogeneity in interventions and outcomes precluded meta-analysis. CONCLUSIONS: Several different blood pressure optimization interventions show promise in reducing exposure to intraoperative hypotension. Nonetheless, the impact of these interventions on clinical outcomes remains unclear. Future trials should assess promising interventions in samples sufficiently large to identify clinically plausible treatment effects on important outcomes.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.

Recent Cannabis Use and Accelerometer-Measured Physical Activity and Sedentary Behavior Among Young-to-Midlife Adults: An Analysis of the National Health and Nutrition Examination Survey from 2011 to 2014.

Introduction: Cannabis use has been associated with reduced physical activity and increased sedentary behavior in adolescents. In adults, however, there is no conclusive evidence of such an association, and existing studies have primarily relied on self-reported activity measures. As cannabis use increases globally, a deeper understanding of its relationship with activity levels may inform clinical counseling and guidelines. This study investigated the association between recent cannabis use and accelerometer-measured activity. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. We included adults in the United States who responded to a cannabis questionnaire and had at least 4 days of activity data from an ActiGraph GT3X+ accelerometer, which comprised participants from 18 to 59 years. The primary exposure was any self-reported cannabis use in the past 30 days. The primary outcome was daily sedentary time and secondary outcomes were daily light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA). Analyses were performed with multivariable quasi-Poisson regression models. Results: Of 4666 included adults, 658 (14.1%) reported recent cannabis use. After covariate adjustment, recent cannabis use was not associated with daily sedentary time (adjusted incidence rate ratio [aIRR] 0.99, 95% confidence interval [CI]: 0.98-1.01) or daily MVPA time (aIRR 1.01, 95% CI: 0.98-1.04). Daily LPA time was 4% greater with recent cannabis use (aIRR 1.04, 95% CI: 1.01-1.06). Conclusion: Recent cannabis use in young to midlife adults was not associated with accelerometer-measured sedentary or MVPA time, but it was associated with a marginal increase in LPA time of unclear clinical significance. Our findings provide evidence against existing concerns that cannabis use independently promotes sedentary behavior and decreases physical activity. Future prospective studies are needed to determine if these findings generalize to specific populations using cannabis including chronic pain patients.

Prevention of persistent pain with lidocaine infusions in breast cancer surgery (PLAN): study protocol for a multicenter randomized controlled trial.

BACKGROUND: Persistent pain is a common yet debilitating complication after breast cancer surgery. Given the pervasive effects of this pain disorder on the patient and healthcare system, post-mastectomy pain syndrome (PMPS) is becoming a larger population health problem, especially as the prognosis and survivorship of breast cancer increases. Interventions that prevent persistent pain after breast surgery are needed to improve the quality of life of breast cancer survivors. An intraoperative intravenous lidocaine infusion has emerged as a potential intervention to decrease the incidence of PMPS. We aim to determine the definitive effects of this intervention in patients undergoing breast cancer surgery. METHODS: PLAN will be a multicenter, parallel-group, blinded, 1:1 randomized, placebo-controlled trial of 1,602 patients undergoing breast cancer surgery. Adult patients scheduled for a lumpectomy or mastectomy will be randomized to receive an intravenous 2% lidocaine bolus of 1.5 mg/kg with induction of anesthesia, followed by a 2.0 mg/kg/h infusion until the end of surgery, or placebo solution (normal saline) at the same volume. The primary outcome will be the incidence of persistent pain at 3 months. Secondary outcomes include the incidence of pain and opioid consumption at 1 h, 1-3 days, and 12 months after surgery, as well as emotional, physical, and functional parameters, and cost-effectiveness. DISCUSSION: This trial aims to provide definitive evidence on an intervention that could potentially prevent persistent pain after breast cancer surgery. If this trial is successful, lidocaine infusion would be integrated as standard of care in breast cancer management. This inexpensive, widely available, and easily administered intervention has the potential to reduce pain and suffering in an already afflicted patient population, decrease the substantial costs of chronic pain management, potentially decrease opioid use, and improve the quality of life in patients. TRIAL REGISTRATION: This trial has been registered on clinicaltrials.gov (NCT04874038, Dr. James Khan. Date of registration: May 5, 2021).

Expression of Cyclin D1 in Urothelial Carcinoma of Urinary Bladder and its Association with Tumour Grade.

Urothelial carcinoma (UC) is the most common malignancy of urinary bladder. It is the 9th leading cause of death worldwide and second most common genitourinary malignancy among male. Incidence is increasing in developing countries like Bangladesh. About 80% of patients are found between 50 to 80 years of age. It is 3-4 times more common in male than in female. Determination of therapeutic strategy and prediction of progression of urothelial carcinoma is a major clinical challenge. Treatment of urothelial carcinoma still now mostly depends on pathological stages. Amplification or genomic alteration of Cyclin D1 (a proto-oncogene) may cause protein overexpression which is frequently realized as a clonal pathology in various human neoplasms including bladder cancer. Evaluation of Cyclin D1 expression is promising for guiding therapeutic strategies, risk stratification and prediction of tumor progression. The aim of the study was to determine the expression of Cyclin D1 in urothelial carcinoma of urinary bladder and its association with tumour grade. This cross-sectional observational study was conducted in Department of Pathology, Dhaka Medical College, Dhaka, Bangladesh from July 2019 to June 2021. Histomorphologically diagnosed 51 urothelial carcinomas were included. Sections were stained with hematoxylin and eosin. Immunostaining with Cyclin D1 antibody was also done. Relevant information was collected and recorded in a predesigned data sheet. Statistical analysis was carried out as required. Mean age ±SD was 57.8±10.55 years. Male female ratio was 4.6:1. In this study 39(76.5%) patients were smoker. Regarding clinical presentations 36(70.6%) patients presented with painless hematuria alone. Lateral wall (64.7%) was the most frequent tumor location. Among 51 cases, 38(74.5%) cases were high grade urothelial carcinoma (HGUC) and 13(25.5%) cases were low grade urothelial carcinoma (LGUC). Considering Cyclin D1 expression, most of the LGUC cases showed high level of expression by both percentage (84.6%) and intensity (84.6%). Most of the HGUC cases showed low level of expression by both percentage (63.2%) and intensity (60.5%). Cyclin D1 showed significant inverse association with HGUC (p<0.05). In urothelial carcinoma of urinary bladder, Cyclin D1 expression was decreased with increasing grade of the tumor. Cyclin D1 expression was inversely associated with tumour grade.

Colorectal Anastomosis Versus Colostomy Creation in High MELD Patients: An ACS-NSQIP Analysis.

BACKGROUND: Liver failure patients are at increased risk of surgical complications. The decision to perform a colonic anastomosis vs a colostomy in urgent colorectal surgery remains unclear. METHODS: The ACS-NSQIP database was queried for patients undergoing nonelective colorectal surgery between 2016 and 2018. MELD score was calculated and stratified into 3 groups. Subgroup analysis of the high-MELD group was performed. RESULTS: Higher MELD scores were associated with significantly higher mortality. Colostomy formation was consistent between intermediate and high-MELD groups. In high-MELD patients, colonic anastomosis was associated with higher mortality than those receiving colostomy (41.1% vs 28.4%, P < .001). Patients receiving colostomy had higher rates of wound complications, but lower rates of return to OR and non-wound complications. Regression analysis revealed that colostomy formation remained an independent predictor of survival (mortality OR = .594, P < .001). DISCUSSION: High-MELD patients undergoing nonelective colorectal surgery have increased risk of complications such as mortality. Patients in this group receiving an anastomosis have increased complications and mortality, and may benefit from colostomy formation.

Preoperative depression and outcomes after metabolic and bariatric surgery: A systematic narrative review.

Preoperative depression is prevalent among patients undergoing metabolic and bariatric surgery (MBS) and is a potentially modifiable risk factor. However, the impact of preoperative depression on MBS outcomes has not been systematically reviewed. A search of MEDLINE, Embase, Cochrane, and PsychINFO (inception to June 2023) was conducted for studies reporting associations between preoperative depression and any clinical or patient-reported outcomes after MBS. Eighteen studies (5 prospective and 13 retrospective) reporting on 5933 participants were included. Most participants underwent gastric bypass or sleeve gastrectomy. Meta-analyses were not conducted due to heterogeneity in reported outcomes; findings were instead synthesized using a narrative and tabular approach. Across 13 studies (n = 3390) the associations between preoperative depression and weight loss outcomes at 6-72 months were mixed overall. This may be related to differences in cohort characteristics, outcome definitions, and instruments used to measure depression. A small number of studies reported that preoperative depression was associated with lower quality of life, worse acute pain, and more perioperative complications after surgery. Most of the included studies were deemed to be at high risk of bias, resulting in low or very low certainty of evidence according to the Risk of Bias In Non-randomized Studies - of Exposure (ROBINS-E) tool. While the impact of preoperative depression on weight loss after MBS remains unclear, there is early evidence that depression has negative consequences on other patient-important outcomes. Adequately powered studies using more sophisticated statistical methods are needed to accurately estimate these associations.

Testosterone Replacement Therapy: Effects on Blood Pressure in Hypogonadal Men.

PURPOSE: While testosterone therapy can improve the various pathologies associated with adult-onset testosterone deficiency (TD), Summary of Product Characteristics (SPC) of five testosterone preparations caution that treatment may be associated with hypertension. This paper evaluates the impact of testosterone undecanoate (TU) on blood pressure (BP) in men with adult-onset TD. MATERIALS AND METHODS: Of 737 men with adult-onset TD in an on-going, observational, prospective, cumulative registry, we studied changes in BP using non-parametric sign-rank tests at final assessment and fixed time points. We used multiple regression analysis to establish factors (baseline BP, age, change/baseline waist circumference [WC] and hematocrit [HCT] and follow-up) potentially associated with BP change in men on TU. RESULTS: TU was associated with significant reductions in systolic, diastolic BP and pulse pressure, regardless of antihypertensive therapy (at baseline or during follow-up), larger reductions were seen with concurrent antihypertensive therapy. In men never on antihypertensive agents, median changes (interquartile range [IQR]) in systolic BP, diastolic BP and pulse pressure were -12.5 (-19.0, -8.0), -8.0 (-14.0, -3.0), and -6.0 (-10.0, -1.0) mmHg, respectively at final assessment, with only baseline BP values inversely associated with these changes (HCT and WC were not significantly associated). In men not on TU, systolic BP, diastolic BP, and pulse pressure significantly increased. In the TU treated men only 1 of the 152 men (not on antihypertensive agents at baseline) were started on antihypertensives during follow-up. In contrast 33 of the 202 men on antihypertensives (at baseline or follow-up) had the antihypertensive agent discontinued by the end of the follow-up. CONCLUSIONS: TU was associated with lowering of BP during follow-up irrespective of antihypertensive therapy, with greater reductions in men with higher baseline BP. In the context of SPC warnings, our long-term data provide reassurance on the effect of TU on BP.

Identifying Oncology Clinical Trial Candidates Using Artificial Intelligence Predictions of Treatment Change: A Pilot Implementation Study.

PURPOSE: Precision oncology clinical trials often struggle to accrue, partly because it is difficult to find potentially eligible patients at moments when they need new treatment. We piloted deployment of artificial intelligence tools to identify such patients at a large academic cancer center. PATIENTS AND METHODS: Neural networks that process radiology reports to identify patients likely to start new systemic therapy were applied prospectively for patients with solid tumors that had undergone next-generation sequencing at our center. Model output was linked to the MatchMiner tool, which matches patients to trials using tumor genomics. Reports listing genomically matched patients, sorted by probability of treatment change, were provided weekly to an oncology nurse navigator (ONN) coordinating recruitment to nine early-phase trials. The ONN contacted treating oncologists when patients likely to change treatment appeared potentially trial-eligible. RESULTS: Within weekly reports to the ONN, 60,199 patient-trial matches were generated for 2,150 patients on the basis of genomics alone. Of these, 3,168 patient-trial matches (5%) corresponding to 525 patients were flagged for ONN review by our model, representing a 95% reduction in review compared with manual review of all patient-trial matches weekly. After ONN review for potential eligibility, treating oncologists for 74 patients were contacted. Common reasons for not contacting treating oncologists included cases where patients had already decided to continue current treatment (21%); the trial had no slots (14%); or the patient was ineligible on ONN review (12%). Of 74 patients whose oncologists were contacted, 10 (14%) had a consult regarding a trial and five (7%) enrolled. CONCLUSION: This approach facilitated identification of potential patients for clinical trials in real time, but further work to improve accrual must address the many other barriers to trial enrollment in precision oncology research.

Assessing and improving radiation safety in cardiac catheterization: a study from Cairo University Hospital.

BACKGROUND: Catheter laboratories are high-radiation exposure environments, especially during X-ray procedures like percutaneous transluminal coronary angioplasty and electrophysiological studies. Radiation exposure poses risks of stochastic (e.g., cancer) and deterministic (e.g., skin changes) effects. This study assessed radiation safety and health practices in a cardiac catheterization unit to optimize radiation safety. A cross-sectional study in Cairo University Hospital (March-September 2019) evaluated 700 patients and healthcare workers. Real-time radiation measurements, educational lectures, and radiation protection measures were implemented in three phases. Data on radiation exposure, procedures, and compliance were collected and analyzed. RESULTS: The total procedure time and fluoroscopy time per cardiologist did not significantly differ between phases, but there was a statistically significant reduction in the mean total cumulative radiation doses between Phase I and Phase III for cardiologists (P = 0.013). Among nurses and technicians, there was no significant difference in radiation doses between the two phases. Significant correlations were found between operators' radiation doses, procedure time, and fluoroscopy time. Patients' radiation doses decreased significantly from Phase I to Phase III, with correlations between dose, procedure time, and gender. Compliance with radiation protection measures was suboptimal. CONCLUSIONS: Compliance with radiation safety standards in the cardiac catheterization unit at the Cairo University Hospital needs improvement. The study highlights the importance of adhering to radiation safety principles and optimizing protective measures to reduce radiation exposure for both patients and healthcare personnel. Despite low compliance, significant reductions in radiation doses were achieved with increased awareness and adherence to specific protection measures. Future efforts should focus on enhancing radiation safety protocols and organ-specific radiation impact assessments.

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.

BACKGROUND: Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam. METHODS: In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects. DISCUSSION: This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.

The Association of Cannabis Use After Discharge From Surgery With Opioid Consumption and Patient-reported Outcomes.

OBJECTIVE: To compare outcomes of patients using versus not using cannabis as a treatment for pain after discharge from surgery. BACKGROUND: Cannabis is increasingly available and is often taken by patients to relieve pain. However, it is unclear whether cannabis use for pain after surgery impacts opioid consumption and postoperative outcomes. METHODS: Using Michigan Surgical Quality Collaborative registry data at 69 hospitals, we analyzed a cohort of patients undergoing 16 procedure types between January 1, 2021, and October 31, 2021. The key exposure was cannabis use for pain after surgery. Outcomes included postdischarge opioid consumption (primary) and patient-reported outcomes of pain, satisfaction, quality of life, and regret to undergo surgery (secondary). RESULTS: Of 11,314 included patients (58% females, mean age: 55.1 years), 581 (5.1%) reported using cannabis to treat pain after surgery. In adjusted models, patients who used cannabis consumed an additional 1.0 (95% CI: 0.4-1.5) opioid pills after surgery. Patients who used cannabis were more likely to report moderate-to-severe surgical site pain at 1 week (adjusted odds ratio: 1.7, 95% CIL 1.4-2.1) and 1 month (adjusted odds ratio: 2.1, 95% CI: 1.7-2.7) after surgery. Patients who used cannabis were less likely to endorse high satisfaction (72.1% vs 82.6%), best quality of life (46.7% vs 63.0%), and no regret (87.6% vs 92.7%) (all P < 0.001). CONCLUSIONS: Patient-reported cannabis use, to treat postoperative pain, was associated with increased opioid consumption after discharge from surgery that was of clinically insignificant amounts, but worse pain and other postoperative patient-reported outcomes.

Psychological Distress After Inpatient Noncardiac Surgery: A Secondary Analysis of the Measurement of Exercise Tolerance Before Surgery Prospective Cohort Study.

OBJECTIVE: To describe the incidence and natural progression of psychological distress after major surgery. BACKGROUND: The recovery process after surgery imposes physical and mental burdens that put patients at risk of psychological distress. Understanding the natural course of psychological distress after surgery is critical to supporting the timely and tailored management of high-risk individuals. METHODS: We conducted a secondary analysis of the "Measurement of Exercise Tolerance before Surgery" multicentre cohort study (Canada, Australia, New Zealand, and the UK). Measurement of Exercise Tolerance before Surgery recruited adult participants (≥40 years) undergoing elective inpatient noncardiac surgery and followed them for 1 year. The primary outcome was the severity of psychological distress measured using the anxiety-depression item of EQ-5D-3L. We used cumulative link mixed models to characterize the time trajectory of psychological distress among relevant patient subgroups. We also explored potential predictors of severe and/or worsened psychological distress at 1 year using multivariable logistic regression models. RESULTS: Of 1546 participants, moderate-to-severe psychological distress was reported by 32.6% of participants before surgery, 27.3% at 30 days after surgery, and 26.2% at 1 year after surgery. Psychological distress appeared to improve over time among females [odds ratio (OR): 0.80, 95% CI: 0.65-0.95] and patients undergoing orthopedic procedures (OR: 0.73, 95% CI: 0.55-0.91), but not among males (OR: 0.87, 95% CI: 0.87-1.07) or patients undergoing nonorthopedic procedures (OR: 0.95, 95% CI: 0.87-1.04). Among the average middle-aged adult, there were no time-related changes (OR: 0.94, 97% CI: 0.75-1.13), whereas the young-old (OR: 0.89, 95% CI: 0.79-0.99) and middle-old (OR: 0.87, 95% CI: 0.73-1.01) had small improvements. Predictors of severe and/or worsened psychological distress at 1 year were younger age, poor self-reported functional capacity, smoking history, and undergoing open surgery. CONCLUSIONS: One-third of adults experience moderate to severe psychological distress before major elective noncardiac surgery. This distress tends to persist or worsen over time among select patient subgroups.

Emerging iron-based mesoporous materials for adsorptive removal of pollutants: Mechanism, optimization, challenges, and future perspective.

Iron-based materials (IBMs) have shown promise as adsorbents due to their unique physicochemical properties. This review provides an overview of the different types of IBMs, their synthesis methods, and their properties. Results found in the adsorption of emerging contaminants to a wide range of IBMs are discussed. The IBMs used were evaluated in terms of their maximum uptake capacity, with special consideration given to environmental conditions such as contact time, solution pH, initial pollutant concentration, etc. The adsorption mechanisms of pollutants are discussed taking into account the results of kinetic, isotherm, thermodynamic studies, surface complexation modelling (SCM), and available spectroscopic data. A current overview of molecular modeling and simulation studies related to density functional theory (DFT), surface response methodology (RSM), and artificial neural network (ANN) is presented. In addition, the reusability and suitability of IBMs in real wastewater treatment is shown. The review concludes with the strengths and weaknesses of current research and suggests ideas for future research that will improve our ability to remove contaminants from real wastewater streams.

Comparison of Hounsfield units and vertebral bone quality score for the prediction of time to pathologic fracture in mobile spine metastases treated with radiotherapy.

OBJECTIVE: Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS: Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1-L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non-tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS: One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257-5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132-4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916-4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009-0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS: The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice, and many other mouse models and AD patients, are generalized EEG spikes (interictal spikes; IIS). Hyperexcitability is also reflected by elevated expression of the transcription factor ΔFosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. We also studied the hilus of the DG because hilar neurons regulate GC excitability. We found reduced expression of the neuronal marker NeuN within hilar neurons in Tg2576 mice, which other studies have shown is a sign of oxidative stress or other pathology. Tg2576 breeding pairs received a diet with a relatively low, intermediate or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ΔFosB expression was reduced, and NeuN expression was restored. Spatial memory improved using the novel object location task. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB and spatial memory in an animal model of AD.

Improving R0 Resection Rates With a Posterior-First, 2-Stage Approach for En Bloc Resection of Locally Advanced Primary and Recurrent Anorectal Cancers Involving the Deep Pelvic Sidewall.

BACKGROUND: Using standard anterior approaches, consistent R0 resection of locally advanced primary and recurrent rectal and anal cancer involving the deep pelvic sidewall may be unattainable. Therefore, to improve R0 resection rates, we have used a posterior-first, then anterior 2-stage approach to resection of tumors in this location. OBJECTIVE: To assess the R0 resection rate and surgical outcomes of the first 10 patients operated on using this approach. DESIGN: We conducted a retrospective case series review of our prospectively maintained surgical pathology and tumor registries. SETTING: This study was conducted at the Mayo Clinic in Rochester, Minnesota. PATIENTS: Ten patients (6 female individuals, median age 53.5 years) with primary or recurrent anal or rectal cancer treated with a posterior-first, then anterior 2-stage approach were identified. MAIN OUTCOME MEASURES: The primary outcome measures were the R0 resection rate and surgical outcomes. RESULTS: An R0 resection was achieved in all 10 patients. Nine patients developed 1 or more 30-day Clavien-Dindo grade III complications. Nine patients developed gluteal wound complications ranging from superficial wound dehiscence to flap necrosis. During the follow-up period, 4 patients were found to have metastatic disease and 1 patient had local re-recurrence. LIMITATIONS: Small cohort with heterogeneous tumors and a short follow-up duration. CONCLUSION: A posterior-first, then anterior 2-stage approach has allowed us to achieve consistent R0 resection margins in locally advanced primary and recurrent rectal and anal cancers involving the deep pelvic sidewall. Poor wound healing of the posterior gluteal incision is a common complication. See Video Abstract. MEJORANDO LAS TASAS DE RESECCIN R CON UN ABORDAJE DE DOS ETAPAS PRIMERO POSTERIOR PARA LA RESECCIN EN BLOQUE DE CNCERES ANORRECTALES PRIMARIOS Y RECURRENTES LOCALMENTE AVANZADOS QUE AFECTAN LA PARED LATERAL PLVICA PROFUNDA: ANTECEDENTES:Utilizando abordajes anteriores estándares, la resección R0 consistente del cáncer de recto y ano primario y recurrente localmente avanzado involucrando la pared lateral pélvica profunda puede ser inalcanzable. Por lo tanto, para mejorar las tasas de resección R0, hemos empleado un abordaje de 2 etapas primero posterior y luego anterior para la resección de tumores en esta ubicación.OBJETIVO:Este estudio tuvo como objetivo evaluar la tasa de resección R0 y los resultados quirúrgicos de los primeros 10 pacientes operados con este abordaje.DISEÑO:Realizamos una revisión retrospectiva de series de casos de nuestros registros de patología quirúrgica y tumores mantenidos prospectivamente.AJUSTE:Este estudio se realizó en la Clínica Mayo en Rochester, Minnesota, EE. UU.PACIENTES:Se identificaron diez pacientes (6 mujeres, mediana de edad 53.5 años) con cáncer anal o rectal primario o recurrente tratados con un abordaje de dos etapas, primero posterior y luego anterior.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas de resultado primarias fueron la tasa de resección R0 y los resultados quirúrgicos.RESULTADOS:Se logró una resección R0 en los 10 pacientes. Nueve pacientes desarrollaron una o más complicaciones de grado III de Clavien-Dindo a los 30 días. Nueve pacientes desarrollaron complicaciones de la herida del glúteo que variaron desde dehiscencia superficial de la herida hasta necrosis del colgajo. Durante el período de seguimiento, se encontró que 4 pacientes tenían enfermedad metastásica y un paciente tuvo recurrencia local.LIMITACIONES:Cohorte pequeño con tumores heterogéneos y corta duración de seguimiento.CONCLUSIÓN:Un abordaje en 2 etapas, primero posterior y luego anterior, nos ha permitido lograr márgenes de resección R0 consistentes en cánceres de recto y anal primarios y recurrentes localmente avanzados que afectan la pared lateral pélvica profunda. La mala cicatrización de la incisión glútea posterior es una complicación común. (Traducción-Dr. Aurian Garcia Gonzalez).