Bone Fragility in High Fat Diet-induced Obesity is Partially Independent of Type 2 Diabetes in Mice.

Obesity and type 2 diabetes (T2D) are risk factors for fragility fractures. It is unknown whether this elevated risk is due to a diet favoring obesity or the diabetes that often occurs with obesity. Therefore, we hypothesized that the fracture resistance of bone is lower in mice fed with a high fat diet (45% kcal; HFD) than in mice that fed on a similar, control diet (10% kcal; LFD), regardless of whether the mice developed overt T2D. Sixteen-week-old, male NON/ShiLtJ mice (resistant to T2D) and age-matched, male NONcNZO10/LtJ (prone to T2D) received a control LFD or HFD for 21 weeks. HFD increased the bodyweight to a greater extent in the ShiLtJ mice compared to the NZO10 mice, while blood glucose levels were significantly higher in NZO10 than in ShiLtJ mice. As such, the glycated hemoglobin A1c (HbA1c) levels exceeded 10% in NZO10 mice, but it remained below 6% in ShiLtJ mice. Diet did not affect HbA1c. HFD lowered trabecular number and bone volume fraction of the distal femur metaphysis (micro-computed tomography or µCT) in both strains. For the femur mid-diaphysis, HFD significantly reduced the yield moment (mechanical testing by three-point bending) in both strains but did not affect cross-sectional bone area, cortical thickness, nor cortical tissue mineral density (µCT). Furthermore, the effect of diet on yield moment was independent of the structural resistance of the femur mid-diaphysis suggesting a negative effect of HFD on characteristics of the bone matrix. However, neither Raman spectroscopy nor assays of advanced glycation end-products identified how HFD affected the matrix. HFD also lowered the resistance of cortical bone to crack growth in only the diabetic NZO10 mice (fracture toughness testing of other femur), while HFD reduced the ultimate force of the L6 vertebra in both strains (compression testing). In conclusion, the HFD-related decrease in bone strength can occur in mice resistant and prone to diabetes indicating that a diet high in fat deleteriously affects bone without necessarily causing hyperglycemia.

Laparoscopic totally extraperitoneal and transabdominal preperitoneal approaches are equally effective for spigelian hernia repair.

INTRODUCTION: Spigelian hernias (SH) are rare intraparietal abdominal wall hernias occurring just medial to the semilunar line. Several small series have reported on laparoscopic SH repair and both totally extraperitoneal (TEP) and transabdominal preperitoneal (TAPP) approaches have been described. However, there are limited outcome data including both of these techniques. We present the largest series to date of laparoscopic SH repair comparing both popular approaches. METHODS: Consecutive patients (n = 77) undergoing laparoscopic SH repair from 2009 to 2019 were identified from a prospectively managed quality database. All procedures were performed at a single institution. Patients were divided based on laparoscopic approach used, TEP group (n = 37) and TAPP group (n = 40). Comparison of patient demographics, surgical characteristics, and post-operative complications between TAPP and TEP groups was made using the Wilcoxon rank-sum and Fisher's exact tests. RESULTS: Individuals undergoing TAPP had higher mean BMI (29.3 ± 5.4 vs. 26.3 ± 5.6 kg/m2; p = 0.019) and were more likely to have had prior abdominal surgery (65% vs 24.3%, (p < 0.001). Mean procedure length was 77 ± 45 min for TAPP repairs and 48 ± 21 for TEP repairs (p = 0.001). TAPP repairs had a significantly longer median LOS than TEP (25 vs. 7 h; p < 0.001). Days of narcotic use were significantly shorter after TEP repair than for TAPP (0 vs. 3; p = 0.007) and return to ADL was significantly shorter after TEP repair than for TAPP (5 vs. 7 days; p = 0.016. There were no significant differences in readmission, reoperations, SSI, or recurrence between the two groups. CONCLUSION: Our large series revealed that both preperitoneal laparoscopic approaches, TEP, and TAPP, for SH repair are equally safe, effective, and can be performed on an outpatient basis. Therefore, we suggest that the approach used for repair should be based on surgeon experience, preference, and individual patient factors.

Short-term quality of life comparison of laparoscopic, open, and robotic incisional hernia repairs.

BACKGROUND: Outcomes of incisional hernia repair (IHR) include recurrence and quality of life (QOL). Operative approaches include laparoscopic, open, and robotic approaches. Data regarding comparative QOL outcomes among these repair types are unknown. Our study evaluates quality of life after three approaches to IHR. STUDY DESIGN: Patients undergoing open (OHR), laparoscopic (LIHR), and robotic extra-peritoneal (RIHR) at a single institution from 2009 to 2019 were reviewed from a prospectively managed quality database. Short-term QOL was compared among the three procedures using the Surgical Outcomes Measurement System (SOMS) and Carolinas Comfort Scale (CCS), objective pain scores and postoperative narcotic use. Data regarding length of stay (LOS), emergency department (ED) visits, readmission, reoperations and surgical site infection (SSI) were also collected. RESULTS: A total of 795 patients undergoing IHR were analyzed (418 open, 300 laparoscopic and 77 robotic). Patient were similar in age, gender and co-morbidities. LIHR patients had higher BMI and RIHR patients had larger hernia and mesh size. LOS was longer and rate of SSI was higher for OIHR compared to laparoscopic and RIHR. Patients undergoing LIHR reported increased narcotic use, Visual Analogue Scale (VAS) and CCS pain scores compared to open and robotic repair. Return to daily activity was 4 days shorter for robotic than open and laparoscopic repair; ED visits, readmissions, reoperations, and other QOL domains were similar. CONCLUSION: Our data suggests that short-term quality of life after robotic extra-peritoneal IHR is improved compared to open and laparoscopic repair. Additional follow up is required to determine differences in long-term QOL after IHR.

Effects of dexamethasone on postoperative urinary retention after laparoscopic inguinal hernia repair.

BACKGROUND: Postoperative urinary retention (POUR) is a complication of laparoscopic inguinal hernia repair (LIHR). Previous research has identified predictive factors of POUR, such as age and history of benign prostatic hyperplasia (BPH). There is currently limited work on preventative measures. We hypothesize dexamethasone, a steroid, reduces POUR rates following LIHR due to its mechanism. METHODS: Consecutive patients (n = 979) undergoing LIHR from 2009 to 2017 at a single institution were selected from a prospectively managed database. All procedures were performed by four general surgeons. Only male patients were selected, as the majority of POUR occurs in males. Patients were retroactively chart reviewed and divided into two groups, dexamethasone use (n = 623) and no dexamethasone use (n = 356). Perioperative factors were compared between groups with Chi-square and independent samples t tests. Univariable and multivariable logistic regression analysis was used to assess whether dexamethasone use was associated with POUR. A subgroup analysis was performed on the dexamethasone group to determine any dose-dependent effects. RESULTS: We found a significant difference in POUR between the dexamethasone group and no dexamethasone group (3.7% vs. 9.8%, p = 0.0001). Patients in the dexamethasone group had a shorter length of stay, and were less likely to have BPH or a Foley placed (all p < 0.05). Age and BMI were similar between groups. Multivariable analysis showed that the use of dexamethasone was associated with a reduced risk of POUR (OR 0.52, 95% CI 0.2-0.97, p = 0.0386), while controlling for factors such as age and BPH. A subgroup analysis examined the effect of dexamethasone per unit (mg) increase. There was no significant association between dexamethasone dose and POUR rates (OR 1.07, 95% CI 0.82-1.38, p = 0.6241). CONCLUSIONS: Patients who received dexamethasone showed a lower rate of POUR regardless of dose. These results suggest dexamethasone can be administered to reduce POUR in males undergoing LIHR.

Does Vibrotactile Stimulation of the Auricular Vagus Nerve Enhance Working Memory? A Behavioral and Physiological Investigation.

Background: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular VNS (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact. Objective: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter. Method: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control). Results: In 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric d ' compared to the baseline but not to the sham. Moreover, we found that the reduction rate of d ' with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham. Conclusion: Our findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory. Highlights: Vibrotactile stimulation of the auricular vagus nerve increases general arousal.Vibrotactile stimulation of the auricular vagus nerve mitigates arousal decreases as subjects continuously perform working memory tasks.6 Hz Vibrotactile auricular vagus nerve stimulation is a potential intervention for enhancing working memory performance.

Does vibrotactile stimulation of the auricular vagus nerve enhance working memory? A behavioral and physiological investigation.

BACKGROUND: Working memory is essential to a wide range of cognitive functions and activities. Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising method to improve working memory performance. However, the feasibility and scalability of electrical stimulation are constrained by several limitations, such as auricular discomfort and inconsistent electrical contact. OBJECTIVE: We aimed to develop a novel and practical method, vibrotactile taVNS, to improve working memory. Further, we investigated its effects on arousal, measured by skin conductance and pupil diameter. METHOD: This study included 20 healthy participants. Behavioral response, skin conductance, and eye tracking data were concurrently recorded while the participants performed N-back tasks under three conditions: vibrotactile taVNS delivered to the cymba concha, earlobe (sham control), and no stimulation (baseline control). RESULTS: In 4-back tasks, which demand maximal working memory capacity, active vibrotactile taVNS significantly improved the performance metric d' compared to the baseline but not to the sham. Moreover, we found that the reduction rate of d' with increasing task difficulty was significantly smaller during vibrotactile taVNS sessions than in both baseline and sham conditions. Arousal, measured as skin conductance and pupil diameter, declined over the course of the tasks. Vibrotactile taVNS rescued this arousal decline, leading to arousal levels corresponding to optimal working memory levels. Moreover, pupil diameter and skin conductance level were higher during high-cognitive-load tasks when vibrotactile taVNS was delivered to the concha compared to baseline and sham. CONCLUSION: Our findings suggest that vibrotactile taVNS modulates the arousal pathway and could be a potential intervention for enhancing working memory.

Optimal approaches to analyzing functional MRI data in glioma patients.

BACKGROUND: Resting-state fMRI is increasingly used to study the effects of gliomas on the functional organization of the brain. A variety of preprocessing techniques and functional connectivity analyses are represented in the literature. However, there so far has been no systematic comparison of how alternative methods impact observed results. NEW METHOD: We first surveyed current literature and identified alternative analytical approaches commonly used in the field. Following, we systematically compared alternative approaches to atlas registration, parcellation scheme, and choice of graph-theoretical measure as regards differentiating glioma patients (N = 59) from age-matched reference subjects (N = 163). RESULTS: Our results suggest that non-linear, as opposed to affine registration, improves structural match to an atlas, as well as measures of functional connectivity. Functionally- as opposed to anatomically-derived parcellation schemes maximized the contrast between glioma patients and reference subjects. We also demonstrate that graph-theoretic measures strongly depend on parcellation granularity, parcellation scheme, and graph density. COMPARISON WITH EXISTING METHODS AND CONCLUSIONS: Our current work primarily focuses on technical optimization of rs-fMRI analysis in glioma patients and, therefore, is fundamentally different from the bulk of papers discussing glioma-induced functional network changes. We report that the evaluation of glioma-induced alterations in the functional connectome strongly depends on analytical approaches including atlas registration, choice of parcellation scheme, and graph-theoretical measures.

The effect of transcutaneous auricular vagus nerve stimulation on cardiovascular function in subarachnoid hemorrhage patients: a safety study.

Introduction: Subarachnoid hemorrhage (SAH) is characterized by intense central inflammation, leading to substantial post-hemorrhagic complications such as vasospasm and delayed cerebral ischemia. Given the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation (taVNS) and its ability to promote brain plasticity, taVNS has emerged as a promising therapeutic option for SAH patients. 3,10,13 However, the effects of taVNS on cardiovascular dynamics in critically ill patients like those with SAH have not yet been investigated. Given the association between cardiac complications and elevated risk of poor clinical outcomes after SAH, it is essential to characterize the cardiovascular effects of taVNS to ensure this approach is safe in this fragile population 5 . Therefore, we assessed the impact of both acute taVNS and repetitive taVNS on cardiovascular function in this study. Methods: In this randomized clinical trial, 24 SAH patients were assigned to either a taVNS treatment or a Sham treatment group. During their stay in the intensive care unit, we monitored patient electrocardiogram (ECG) readings and vital signs. We compared long-term changes in heart rate, heart rate variability, QT interval, and blood pressure between the two groups. Additionally, we assessed the effects of acute taVNS by comparing cardiovascular metrics before, during, and after the intervention. We also explored rapidly responsive cardiovascular biomarkers in patients exhibiting clinical improvement. Results: We found that repetitive taVNS did not significantly alter heart rate, corrected QT interval, blood pressure, or intracranial pressure. However, taVNS increased overall heart rate variability and parasympathetic activity from 5-10 days after initial treatment, as compared to the sham treatment. Acutely, taVNS increased heart rate, blood pressure, and peripheral perfusion index without affecting the corrected QT interval, intracranial pressure, or heart rate variability. The acute post-treatment elevation in heart rate was more pronounced in patients who experienced a decrease of more than 1 point in their Modified Rankin Score at the time of discharge. Conclusions: Our study found that taVNS treatment did not induce adverse cardiovascular effects, such as bradycardia or QT prolongation, supporting its development as a safe immunomodulatory treatment approach for SAH patients. The observed acute increase in heart rate after taVNS treatment may serve as a biomarker for SAH patients who could derive greater benefit from this treatment. Trial registration: NCT04557618.

Predictors for recurrence after open umbilical hernia repair in 979 patients.

BACKGROUND: Our study aims were to evaluate factors that predict recurrence after open umbilical hernia repair with either mesh or primary closure. METHODS: Consecutive patients (n = 1,125) undergoing open umbilical hernia repair from 2009 to 2018 were identified from a prospectively managed, quality database. Kaplan-Meier curves and log-rank tests were used to analyze recurrence-free survival for preoperative, intraoperative, and postoperative factors. Univariable and multivariable Cox regression was used to analyze recurrence-free survival by age, sex, body mass index, concurrent laparoscopic inguinal hernia repair, smoking status, diabetes, postoperative infection, hernia size in greatest dimension, and type of repair. RESULTS: The overall recurrence rate was 3.3% with a median follow-up of 14 months. Univariable analysis revealed a difference in recurrence-free survival for current smoking (P = .039), diabetes (P = .007), higher body mass index (P = .057), and postoperative infection (P < .001). Multivariable analysis indicated higher body mass index (P = .007), concurrent laparoscopic inguinal hernia repair (P = .044), current smoking status (P = .020), diabetes (P = .021), and a primary closure repair of hernias ≥1.5 cm (P = .001) had a greater risk of recurrence. Postoperative infection showed an association with recurrence (P = .053). CONCLUSION: Our results indicate higher body mass index, concurrent laparoscopic inguinal hernia repair, current smoking, diabetes, primary closure repair of hernias ≥1.5 cm, and postoperative infection were associated with a greater risk of recurrence after open umbilical hernia repair.

Laparoscopic inguinal hernia repair after prostatectomy: Evaluating safety, efficacy, and efficiency.

BACKGROUND: For many surgeons, a prior prostatectomy is considered a contraindication to laparoscopic totally extraperitoneal hernia repair. This study aims to evaluate the safety, efficacy, and efficiency of totally extraperitoneal in these patients. METHODS: This is a review of a prospectively collected hernia database evaluating patients who underwent totally extraperitoneal repair between October 2009 and March 2018. Patients with prior prostatectomy were matched to controls without prior prostatectomy. Secondary analysis compared the case group to patients who underwent open hernia repair. RESULTS: In the study, 1,751 patients underwent laparoscopic totally extraperitoneal repair. Thirty patients with a prior prostatectomy were matched to 90 controls. Operative duration was greater in the prostatectomy group (56 vs 36 minutes, P < .0001) and more peritoneal tears occurred (40% vs 12%, P = .002). Duration of stay, return to activity, complications, and rates of recurrence and chronic pain were equivalent. When compared with prior prostatectomy patients who underwent open hernia repair, the laparoscopic totally extraperitoneal group had equivalent rates of complications and outcomes with a faster return to activities of daily living (3 vs 7 days P = .007). CONCLUSION: Despite a more difficult dissection, laparoscopic totally extraperitoneal repair in patients with prior prostatectomy is safe, efficacious, and efficient. In addition, totally extraperitoneal offers similar outcomes to open repair with a quicker recovery in this patient population.

Improved p50 auditory gating with ondansetron in medicated schizophrenia patients.

OBJECTIVE: Most schizophrenia patients have a deficit in auditory sensory gating, which appears to be mediated by the alpha-7 nicotinic receptor, that is not improved with conventional antipsychotic treatment. This study examined the effects of ondansetron, a highly selective 5-HT3 antagonist, on the P50 auditory evoked potential. METHOD: Eight medicated outpatients with schizophrenia were given either ondansetron (16 mg) or placebo in a double-blind, placebo-controlled design. Evoked potentials were recorded at baseline and 1 hour, 2 hours, and 3 hours after receipt of drug. RESULTS: There was a highly significant improvement in P50 gating after ondansetron treatment. The maximal treatment difference was at 2 hours posttreatment (ondansetron: mean=41.4%, SD=39.7%; placebo: mean=80.2%, SD=21.3%). CONCLUSIONS: Ondansetron significantly enhanced P50 auditory gating in schizophrenia patients treated with typical antipsychotics.