Hepatic protein kinase Cbeta deficiency mitigates late-onset obesity.

Although aging is associated with progressive adiposity and a decline in liver function, the underlying molecular mechanisms and metabolic interplay are incompletely understood. Here, we demonstrate that aging induces hepatic protein kinase Cbeta (PKCß) expression, while hepatocyte PKCß deficiency (PKCßHep-/-) in mice significantly attenuates obesity in aged mice fed a high-fat diet. Compared with control PKCßfl/fl mice, PKCßHep-/- mice showed elevated energy expenditure with augmentation of oxygen consumption and carbon dioxide production which was dependent on ß3-adrenergic receptor signaling, thereby favoring negative energy balance. This effect was accompanied by induction of thermogenic genes in brown adipose tissue (BAT) and increased BAT respiratory capacity, as well as a shift to oxidative muscle fiber type with an improved mitochondrial function, thereby enhancing oxidative capacity of thermogenic tissues. Furthermore, in PKCßHep-/- mice, we determined that PKCß overexpression in the liver mitigated elevated expression of thermogenic genes in BAT. In conclusion, our study thus establishes hepatocyte PKCß induction as a critical component of pathophysiological energy metabolism by promoting progressive hepatic and extrahepatic metabolic derangements in energy homeostasis, contributing to late-onset obesity. These findings have potential implications for augmenting thermogenesis as a means of combating aging-induced obesity.

The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness.

Muscle fitness and mass deteriorate under the conditions of obesity and aging for reasons yet to be fully elucidated. Herein, we describe a novel pathway linking peripheral nutrient sensing and skeletal muscle function through the sweet taste receptor TAS1R2 and the involvement of ERK2-PARP1-NAD signaling axis. Muscle-specific deletion of TAS1R2 (mKO) in mice produced elevated NAD levels due to suppressed PARP1 activity, improved mitochondrial function, increased muscle mass and strength, and prolonged running endurance. Deletion of TAS1R2 in obese or aged mice also ameliorated the decline in muscle mass and fitness arising from these conditions. Remarkably, partial loss-of-function of TAS1R2 (rs35874116) in older, obese humans recapitulated the healthier muscle phenotype displayed by mKO mice in response to exercise training. Our findings show that inhibition of the TAS1R2 signaling in skeletal muscle is a promising therapeutic approach to preserve muscle mass and function.

Distinct Effects of High-Fat and High-Phosphate Diet on Glucose Metabolism and the Response to Voluntary Exercise in Male Mice.

The prevalence of metabolic diseases is rapidly increasing and a principal contributor to this is diet, including increased consumption of energy-rich foods and foods with added phosphates. Exercise is an effective therapeutic approach to combat metabolic disease. While exercise is effective to combat the detrimental effects of a high-fat diet on metabolic health, the effects of exercise on a high-phosphate diet have not been thoroughly investigated. Here, we investigated the effects of a high-fat or high-phosphate diet in the presence or absence of voluntary exercise on metabolic function in male mice. To do this, mice were fed a low-fat, normal-phosphate diet (LFPD), a high-phosphate diet (HPD) or a high-fat diet (HFD) for 6 weeks and then subdivided into either sedentary or exercised (housed with running wheels) for an additional 8 weeks. An HFD severely impaired metabolic function in mice, increasing total fat mass and worsening whole-body glucose tolerance, while HPD did not induce any notable effects on glucose metabolism. Exercise reverted most of the detrimental metabolic adaptations induced by HFD, decreasing total fat mass and restoring whole-body glucose tolerance and insulin sensitivity. Interestingly, voluntary exercise had a similar effect on LFPD and HPD mice. These data suggest that a high-phosphate diet does not significantly impair glucose metabolism in sedentary or voluntary exercised conditions.

Cardiac-derived TGF-ß1 confers resistance to diet-induced obesity through the regulation of adipocyte size and function.

Regulation of organismal homeostasis in response to nutrient availability is a vital physiological process that involves inter-organ communication. Understanding the mechanisms controlling systemic cross-talk for the maintenance of metabolic health is critical to counteract diet-induced obesity. Here, we show that cardiac-derived transforming growth factor beta 1 (TGF-ß1) protects against weight gain and glucose intolerance in mice subjected to high-fat diet. Secretion of TGF-ß1 by cardiomyocytes correlates with the bioavailability of this factor in circulation. TGF-ß1 prevents adipose tissue inflammation independent of body mass and glucose metabolism phenotypes, indicating protection from adipocyte dysfunction-driven immune cell recruitment. TGF-ß1 alters the gene expression programs in white adipocytes, favoring their fatty acid oxidation and consequently increasing their mitochondrial oxygen consumption rates. Ultimately, subcutaneous and visceral white adipose tissue from cadiac-specific TGF-ß1 transgenic mice fail to undergo cellular hypertrophy, leading to reduced overall adiposity during high-fat feeding. Thus, TGF-ß1 is a critical mediator of heart-fat communication for the regulation of systemic metabolism.

L5 Fracture Dislocation Secondary to Cold Abscess Treated by Posterior Corpectomy With Expandable Cage Placement.

Infections of the lumbar spine can have serious sequelae, including neurological deficits, paralysis, and death. Prolonged infection can result in fracture of the vertebrae, local abscesses, and infiltration and compression of local vascular structures. In cases with significant instability or neurological compromise, a common treatment approach is vertebral corpectomy with interbody cage followed by long-term antibiotics. The following case describes a patient with a three-month history of progressively worsening lower back pain, lower extremity radiculopathy, and bilateral lower extremity edema, in the setting of a nontraumatic three-column fracture dislocation of L5 with grade 4 retrolisthesis of L4 on L5. A posterior-only corpectomy with placement of an expandable cage, to be followed by pedicle screw placement from L3-S1/ilium, was performed. The procedure was successful, and the patient was discharged on postoperative day 5 without complication and with resolution of his edema. Histopathological analysis demonstrated acute and chronic inflammation, but extensive tests and cultures failed to identify a causative organism. This case highlights several interesting features, including a technically challenging and seldom-performed procedure, as well as the ability of lumbar spinal infections to present with leg edema due to involvement the inferior vena cava and iliac vessels. For patients with three-column fractures of L5 due to an inflammatory process or trauma, a single-stage posterior corpectomy with placement of an expandable cage may be considered as an appropriate treatment option.

How the elderly fare after brain tumor surgery compared to younger patients within a 30-day follow-up: A National surgical Quality Improvement Program analysis of 30,183 cases.

The growing elderly population in Western societies has led to an increasing number of primary brain tumors occurring in patients beyond the age of 65. The purpose of this study was to assess and compare the safety, efficacy, and outcomes of oncological craniotomy procedures between patients above and below 65 years. We performed a retrospective analysis of the ACS-NSQIP database to identify patients undergoing supratentorial and infratentorial tumor excisions by neurosurgeons between 2008 and 2016. We stratified them based on a cutoff age of 65 years and analyzed for minor and major complications, reoperation, the total length of hospital stay, and mortality within a standardized 30-day follow-up. Among the 30,183 analyzed patients, 9,652 (32%) were elderly (age ≥ 65). The bivariate analysis demonstrated significantly increased risk of complications, including major and minor complications and mortality in patients with metabolic syndrome, preoperative steroid use, and ASA classification ≥3. (p-value ≤ 0.001***). After controlling for confounding variables in our logistic regression models, older age, metabolic syndrome, extended operative time beyond 5 h, dependent functional health status, ASA class ≥3, steroid use pre-operatively, and black/African American race were found to be significant predictors of major and minor complication. Our study provides a comprehensive analysis of perioperative risk factors and predictors of adverse outcomes following craniotomy for supratentorial and infratentorial tumors in elderly patients. We identified increased age as an independent risk factor for minor and major adverse events as well as extended hospitalization.

Effect of an additional neurosurgical resident on procedure length, operating room time, estimated blood loss, and post-operative length-of-stay.

Introduction: Neurosurgical residency training is costly, with expenses largely borne by the academic institutions that train residents. One expense is increased operative duration, which leads to poorer patient outcomes. Although other studies have assessed the effect of one resident assisting, none have investigated two residents; thus, we sought to investigate if two residents versus one scrubbed-in impacted operative time, estimated blood loss (EBL), and length-of-stay (LOS).Methods: In this retrospective review of patients who underwent a neurosurgical procedure involving one or two residents between January 2013 and April 2016, we performed multivariable linear regression to determine if there was an association between resident participation and case length, operating room time, EBL, and LOS. We also included patient demographics, attending surgeon, day of the week, start time, pre-operative LOS, procedure performed, and other variables in our model. Only procedures performed at least 40 times during the study period were analyzed.Results: Of 860 procedures that met study criteria, 492 operations were one of six procedures performed at least 40 times, which were anterior cervical discectomy and fusion, cerebrospinal fluid (CSF) shunt insertion, CSF shunt revision, lumbar laminectomy, intracranial hematoma evacuation, and non-skull base, supratentorial parenchymal brain tumor resection. An additional resident was associated with a 35.1-min decrease (p = .01) in operative duration for lumbar laminectomies. However, for intracranial hematoma evacuations, an extra resident was associated with a 24.1 min increase (p = .03) in procedural length. There were no significant differences observed in the other four surgeries.Conclusion: An additional resident may lengthen duration of intracranial hematoma evacuations. However, two residents scrubbed-in were associated with decreased lumbar laminectomy duration. Overall, an extra resident does not increase procedural duration, total operating room utilization, EBL, or post-operative LOS. Allowing two residents to scrub in may be a safe and cost-effective method of educating neurosurgical residents.

A Systematic Review of Ion Radiotherapy in Maintaining Local Control Regarding Atypical and Anaplastic Meningiomas.

OBJECTIVE: Atypical and anaplastic meningiomas, unlike their benign counterparts, are highly aggressive, locally destructive, and likely to recur after treatment. These diseases are difficult to definitively treat with traditional radiotherapy without injuring adjacent brain parenchyma. The physical properties of ion radiotherapy allows for treatment plans that avoid damaging critical neural structures. The objectives of this systematic review were to evaluate the use and efficacy of ion radiotherapy in the treatment of atypical and anaplastic meningiomas. METHODS: We performed a systematic review of the literature by querying the PubMed and Ovid databases to identify and examine literature addressing the efficacy of ion radiotherapy in maintaining long-term local tumor control for patients with atypical or anaplastic meningiomas. The outcome of interest was rate of local tumor control at 5 years after ion radiotherapy. RESULTS: Across the included studies, proton therapy delivered a mean local control rate of 59.62% after 5 years. Carbon ion radiotherapy studies showed local control rates of 95% and 63% at 2 years for grade II and III meningiomas, respectively. In contrast, carbon ion radiotherapy studies that failed to differentiate between atypical and anaplastic meningiomas produced a local control rate of 33% at 2 years. CONCLUSIONS: Proton and carbon ion radiotherapy maintain comparable rates of local control to conventional photon therapy and allow for more targeted treatment plans that may limit excess radiation damage. Although additional prospective trials are needed, ion therapy represents a burgeoning field in the treatment of atypical and anaplastic meningiomas.

Cefazolin versus vancomycin for neurosurgical operative prophylaxis - A single institution retrospective cohort study.

OBJECTIVES: Cefazolin and vancomycin are common choices for neurosurgical antimicrobial prophylaxis. Cefazolin is typically first-line due to its lower toxicity profile and specificity for gram-positives such as skin commensals, while vancomycin is often reserved for patients with cephalosporin or penicillin allergies. However, one randomized clinical trial demonstrated superiority of vancomycin for cerebrospinal fluid (CSF) shunt insertions at a hospital with a high prevalence of methicillin-resistance Staphylococcus aureus (MRSA). We aimed to evaluate the association of prophylaxis choice and incidence of surgical site infection (SSI) at our own institution. PATIENTS AND METHODS: This was a retrospective cohort study of patients who underwent a neurosurgical operation from January 2013 to April 2016 at one particular hospital belonging to our institution. We included patients who received either only cefazolin or only vancomycin as their pre-incisional prophylaxis. Vancomycin was substituted for cefazolin in patients with known penicillin or cephalosporin allergy. Procedures requiring multiple attending surgeons were excluded. We defined a SSI as a confirmed culture isolated from the wound, implant (if pertinent), or CSF (if pertinent) within a year of surgery. Multivariable logistic regression was performed with consideration of antibiotic, operation performed, wound class, and procedure length. RESULTS: A total of 859 operations met study criteria; 664 patients received Cefazolin, and 195 received Vancomycin. We identified 22 SSIs, with 14 in the cefazolin (2.2%) and 8 in the vancomycin (4.1%) group. Upon logistic regression, there was no significant association of vancomycin substitution with incidence of SSIs between the two groups (odds ratio, 1.59; 95% CI, 0.42-6.00, p = .49). In the cefazolin group, 8/14 cultures were positive for S. aureus compared to 1/8 of the vancomycin group. CONCLUSIONS: There was no significant difference in neurosurgical site infection incidence when vancomycin prophylaxis was substituted for cefazolin. S. aureus was isolated from patients who received cefazolin at a higher rate although this was not statistically significant. At our institution, S. aureus makes up 36% of isolated organisms from inpatient and intensive care units. Institutions should consider their own investigations into local antibiograms, SSI rates, and choice of prophylaxis.

Metabolic Syndrome Associated with Increased Rates of Medical Complications After Intracranial Tumor Resection.

BACKGROUND: When diagnosed simultaneously, obesity, diabetes, and hypertension form a medical constellation called metabolic syndrome (MetS). The prevalence of MetS in Western cultures has been on a steady increase and MetS has been associated with increased postoperative complications in multiple surgical settings. OBJECTIVE: In this study, we evaluate the relationship between MetS and the outcomes of craniotomy for supratentorial brain tumor. METHODS: Cases of craniotomy for supratentorial brain tumors were extracted from the American College of Surgeons National Surgical Quality Improvement Program for 2012-2016. The 15,136 patients identified were divided into 2 cohorts based on the presence (4.1%) or absence (95.9%) of MetS. We compared the 2 cohorts for preoperative comorbidities, intraoperative details, and postoperative morbidity and mortality. RESULTS: Patients in the MetS+ cohort were significantly older (63.4 vs. 56.1 years) and were more likely to show comorbidities of various organ systems (all P ≤ 0.05). However, operative times were similar (P = 0.573). The number of medical complications was almost double in patients with MetS (15.8% vs. 8.5%; P ≤ 0.001). Unplanned readmissions (14.6% vs. 10.4%; P = 0.004), reoperations (6.9% vs. 4.6%; P = 0.007), and mortality (5.6% vs. 2.9%; P ≤ 0.001) were also more frequent in our MetS+ group. Nevertheless, surgical complications localized to the operative site were not statistically increased (7.4% vs. 5.8%; P = 0.098). CONCLUSIONS: A diagnosis of MetS does not seem to be associated with increased rates of surgical site events. However, neurosurgeons should be aware that these patients have a significantly higher likelihood of general medical complications, readmissions, reoperations, and death.

Microsurgical Removal of Microcatheter in the Middle Cerebral Artery During Resection of an Arteriovenous Malformation Resection.

Surgical resection is the current standard of therapy for the treatment of arteriovenous malformation (AVM). Endovascular embolization is commonly used as an adjunct prior to surgical resection because it is believed to reduce the risk of intraoperative bleeding. Embolization has been associated with other complications including visual deficits, vessel perforation, and catheter adhesion. Catheter adhesion in which retained segments are contained within the embolization cast are not necessarily cause for concern, but retention of larger portions may confer an increased risk of thrombus formation. Such cases warrant the removal of the retained segments or the patient may suffer serious complications including death related to cerebrovascular events. In this case report, we describe a unique case of catheter adhesion in which the extension of the feeding catheter and the length of the introducer was left in its entirety down to the entry portion at the level of the groin and later retrieved in its entirety by craniotomy.

Comparing Radiation Dose from Conventional Fluoroscopy to Intraoperative Cone Beam CT (O-arm) during Percutaneous Lesioning Procedures of the Gasserian Ganglion.

INTRODUCTION: The use of intraoperative CT-guidance during the percutaneous treatment of trigeminal neuralgia has become increasingly popular due to the greater ease of foramen ovale cannulation and decreased procedure times. Concerns regarding radiation dose to the patient, however, remain unaddressed. We sought to compare the emitted radiation dose from fluoroscopy with intraoperative CT for these procedures. METHODS: A retrospective review of percutaneous lesioning procedures for trigeminal neuralgia performed between 2010 until 2012 at our institution was conducted and radiation doses to the patient were recorded. We subsequently simulated four separate percutaneous trigeminal rhizotomies using the O-arm intraoperative CT (Medtronics, Minneapolis, MN, USA) to cannulate the foramen ovale bilaterally in two formalin-fixed cadaver heads. RESULTS: Seventeen successful percutaneous treatments for trigeminal neuralgia were performed during the study period. Eleven procedures containing complete records were included in the final analysis. For procedures using fluoroscopy, the mean dosage was 15.2 mGys (range: 1.15 - 47.95, 95% CI 7.34 - 22.99). Radiation dosage from the O-arm imaging system was 16.55 mGy for all four cases. An unequal variance t-test did not reach statistical significance (p=0.42). CONCLUSIONS: We did not observe a significant difference in radiation dose delivered to subjects when comparing CT-guided foramen ovale cannulation relative to fluoroscopy for percutaneous lesioning of the Gasserian ganglion. Additional study is required under operational settings.

Virtual reality spine surgery simulation: an empirical study of its usefulness.

OBJECTIVE: This study explores the usefulness of virtual simulation training for learning to place pedicle screws in the lumbar spine. METHODS: Twenty-six senior medical students anonymously participated and were randomized into two groups (A = no simulation; B = simulation). Both groups were given 15 minutes to place two pedicle screws in a sawbones model. Students in Group A underwent traditional visual/verbal instruction whereas students in Group B underwent training on pedicle screw placement in the ImmersiveTouch simulator. The students in both groups then placed two pedicle screws each in a lumbar sawbones models that underwent triplanar thin slice computerized tomography and subsequent analysis based on coronal entry point, axial and sagittal deviations, length error, and pedicle breach. The average number of errors per screw was calculated for each group. Semi-parametric regression analysis for clustered data was used with generalized estimating equations accommodating a negative binomial distribution to determine any statistical difference of significance. RESULTS: A total of 52 pedicle screws were analyzed. The reduction in the average number of errors per screw after a single session of simulation training was 53.7% (P  =  0.0067). The average number of errors per screw in the simulation group was 0.96 versus 2.08 in the non-simulation group. The simulation group outperformed the non-simulation group in all variables measured. The three most benefited measured variables were length error (86.7%), coronal error (71.4%), and pedicle breach (66.7%). CONCLUSIONS: Computer-based simulation appears to be a valuable teaching tool for non-experts in a highly technical procedural task such as pedicle screw placement that involves sequential learning, depth perception, and understanding triplanar anatomy.

Hospital and medical care days in pancreatic cancer.

BACKGROUND: Little is known about resource utilization (number of days in the hospital or medical care) between diagnosis and death in patients with pancreatic cancer. METHODS: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data, we identified 25,476 patients with pancreatic cancer (1992-2005). Hospital and medical care days per person-month from the time of diagnosis were described, stratified by stage, treatment, and survival duration. RESULTS: Hospital/medical care days vary by length of survival and treatment strategy in patients with pancreatic cancer. For all stages, patients were in the hospital a mean of 6.4 days and received medical care a total of 9.0 days in the first month after diagnosis, decreasing to 1.7 and 3.7 days per month, respectively, by the end of the first year. Hospital/medical care days per month of life were higher in patients with shorter survival but increased sharply at the end of life in all patients, regardless of duration of survival. In patients with locoregional disease, resection was associated with a higher number of hospital/medical care days during the first 4 months after diagnosis, but fewer at the end of the first year. For distant disease, hospital days were similar but days in medical care were higher for patients receiving chemotherapy, increasing especially at the end of life. CONCLUSIONS: This study is the first to quantify hospital/medical care days in patients with pancreatic cancer by stage, treatment, and survival. This information will provide realistic expectations and allow for treatment decisions based on patient preferences.