FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling.

Dietary protein restriction induces adaptive changes in food preference, increasing protein consumption over carbohydrates or fat. We investigated whether motivation and reward signaling underpin these preferences. In an operant task, protein-restricted male mice increased their responding for liquid protein rewards, but not carbohydrate, fat, or sweet rewards. The protein restriction-induced increase in operant responding for protein was absent in Fgf21-KO mice and mice with neuron-specific deletion of the FGF21 co-receptor beta-Klotho (KlbCam2ka) mice. Fiber photometry recording of VTA dopamine neurons revealed that oral delivery of maltodextrin triggered a larger activation of dopamine neurons as compared to casein in control-fed mice, while casein produced a larger response in protein-restricted mice. This restriction-induced shift in nutrient-specific VTA dopamine signaling was lost in Fgf21-KO mice. These data demonstrate that FGF21 acts in the brain to induce a protein-specific appetite by specifically enhancing the reward value of protein-containing foods and the motivation to consume them.

Limitations of the 2015-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database for emergency bariatric operations.

BACKGROUND: The Metabolic and Bariatric Surgery Quality Improvement Project (MBSAQIP) is the largest bariatric surgery-specific clinical data set. OBJECTIVES: In 2020, the definition of emergency cases was altered to include only revisional or conversion cases and not primary cases. The aim of this study was to examine how this change affects the utility of the data set for emergency case tracking. SETTING: MBSAQIP database. METHODS: Emergency cases were extracted from available MBSAQIP data (2015-2021). A comparison of co-morbidity profiles was done, specifically before and after the recent change to how "emergency" is defined in the data set. RESULTS: Eleven thousand and twenty-nine of the 1,048,575 total cases were coded as "emergency cases." From 2015 to 2019, 10,574 emergency cases were performed (∼2115 cases/yr), markedly decreasing in 2020 and 2021 to 455 cases (∼228 cases/yr). Before 2020, the most common procedures were the unlisted procedure of the stomach (45.14%, n = 3101), gastric band removal (25.3%, n = 2676), and reduction of internal hernia (11.8%, n = 1244). Between 2020 and 2021, this distribution changed with Roux-en-Y gastric bypass (RYGB), the most common emergency procedure (29.23%, n = 133). As expected from the change that captured only revisional cases, the average operative length was greater between 2020 and 2021 (127.6 versus 86.5 min). CONCLUSIONS: Capturable emergency cases declined in 2020, a trend related to changing the definition of emergency as part of MBSAQIP standards. This change excludes data on internal hernia reduction and does not likely reflect a real change in the prevalence of emergency bariatric cases. Because capture for emergency cases has diminished, so has any prior utility of using MBSAQIP data for studying emergency cases.

Bariatric surgery alters mitochondrial function in gut mucosa.

BACKGROUND: The obesity pandemic has worsened global disease burden, including type 2 diabetes, cardiovascular disease, and cancer. Metabolic/bariatric surgery (MBS) is the most effective and durable obesity treatment, but the mechanisms underlying its long-term weight loss efficacy remain unclear. MBS drives substrate oxidation that has been linked to improvements in metabolic function and improved glycemic control that are potentially mediated by mitochondria-a primary site of energy production. As such, augmentation of intestinal mitochondrial function may drive processes underlying the systemic metabolic benefits of MBS. Herein, we applied a highly sensitive technique to evaluate intestinal mitochondrial function ex vivo in a mouse model of MBS. METHODS: Mice were randomized to surgery, sham, or non-operative control. A simplified model of MBS, ileal interposition, was performed by interposition of a 2-cm segment of terminal ileum into the proximal bowel 5 mm from the ligament of Treitz. After a four-week recovery period, intestinal mucosa of duodenum, jejunum, ileum, and interposed ileum were assayed for determination of mitochondrial respiratory function. Citrate synthase activity was measured as a marker of mitochondrial content. RESULTS: Ileal interposition was well tolerated and associated with modest body weight loss and transient hypophagia relative to controls. Mitochondrial capacity declined in the native duodenum and jejunum of animals following ileal interposition relative to controls, although respiration remained unchanged in these segments. Similarly, ileal interposition lowered citrate synthase activity in the duodenum and jejunum following relative to controls but ileal function remained constant across all groups. CONCLUSION: Ileal interposition decreases mitochondrial volume in the proximal intestinal mucosa of mice. This change in concentration with preserved respiration suggests a global mucosal response to segment specific nutrition signals in the distal bowel. Future studies are required to understand the causes underlying these mitochondrial changes.

The Vagus Nerve Mediates Gut-Brain Response to Duodenal Nutrient Administration.

BACKGROUND: Obesity contributes significant disease burden worldwide, including diabetes, cardiovascular disease, and cancer. While bariatric surgery is the most effective and durable obesity treatment, the mechanisms underlying its effects remain unknown. Although neuro-hormonal mechanisms have been suspected to mediate at least some of the gut-brain axis changes following bariatric surgery, studies examining the intestine and its regionally specific post-gastric alterations to these signals remain unclear. MATERIALS AND METHODS: Vagus nerve recording was performed following the implantation of duodenal feeding tubes in mice. Testing conditions and measurements were made under anesthesia during baseline, nutrient or vehicle solution delivery, and post-delivery. Solutions tested included water, glucose, glucose with an inhibitor of glucose absorption (phlorizin), and a hydrolyzed protein solution. RESULTS: Vagus nerve signaling was detectable from the duodenum and exhibited stable baseline activity without responding to osmotic pressure gradients. Duodenal-delivered glucose and protein robustly increased vagus nerve signaling, but increased signaling was abolished during the co-administration of glucose and phlorizin. DISCUSSION: Gut-brain communication via the vagus nerve emanating from the duodenum is nutrient sensitive and easily measurable in mice. Examination of these signaling pathways may help elucidate how the nutrient signals from the intestine are altered when applied to obesity and bariatric surgery mouse models. Future studies will address quantifying the changes in neuroendocrine nutrient signals in health and obesity, with specific emphasis on identifying the changes associated with bariatric surgery and other gastrointestinal surgery.

Parenteral Nutrition Total Energy Dosing and Risk for Central Line-Associated Bloodstream Infection: A Case-Control Study.

Background: Central line-associated bloodstream infection (CLABSI) is a complication of central venous access devices used for parenteral nutrition (PN). PN overfeeding is associated with increased adverse effects; however, whether risk for CLABSI is influenced by PN dosing is uncertain. Objective: The purpose of the study was to assess differences in CLABSI risk associated with recommended total energy dosing in hospitalized adult patients receiving PN. Methods: A case-control study was conducted in a single United States Veterans Health Administration health system to assess the potential CLABSI risk factor of weight-based PN kilocalorie dosing. Hospitalized adult patients who developed CLABSI while receiving PN were identified and compared to a control group of patients who did not develop CLABSI. The exposures evaluated were overfeeding, defined as greater than 30 kcal/kg/day, and underfeeding, defined as less than 20 kcal/kg/day. Results: Twenty-nine cases of CLABSI were identified and compared with 274 controls. Odds of CLABSI were significantly higher in patients receiving greater than 30 kcal/kg/day (OR, 3.63; 95% CI, 1.55-8.48; P < .01). No significant difference in odds was found for patients receiving less than 20 kcal/kg/day (OR, .74; 95% CI, 0.21-2.57; P = .63). Conclusion: Increased risk for CLABSI in hospitalized adult patients receiving PN was found to be associated with overfeeding, but not underfeeding. These results may aid clinicians in the management of patients requiring PN and in the generation of hypothesis for future investigations.

Risk Factors for Hypoglycemia During Treatment of Hyperglycemic Crises.

Objective: Diabetic ketoacidosis and hyperosmolar hyperglycemic state are life-threatening hyperglycemic crises often requiring intensive care unit (ICU) management. Treatment includes intravenous (IV) insulin with a transition to subcutaneous (SC) insulin upon resolution. Hypoglycemia is a common complication associated with treatment of hyperglycemic crises, but risk factors have not been well established. This study aimed to assess risk factors associated with hypoglycemia during treatment for hyperglycemic crises. Methods: This case-control study included ICU patients admitted with hyperglycemic crises at a single Veterans Affairs health system from 1 January 2013 to 31 March 2020. Patients who developed hypoglycemia during insulin treatment were compared with a control group. Odds of hypoglycemia were assessed based on risk factors, including BMI, comorbidities, and type of SC insulin used. Results: Of the 216 cases of hyperglycemic crises included, hypoglycemia occurred in 61 cases (44 on SC insulin, 11 on IV insulin, and 6 on both). Odds for hypoglycemia were significantly higher for underweight patients (odds ratio 4.52 [95% CI 1.05-19.55]), type 1 diabetes (4.02 [2.09-7.73]), chronic kidney disease (1.94 [1.05-3.57]), those resumed on the exact chronic SC insulin regimen following resolution (2.91 [1.06-7.95]), and patients who received NPH versus glargine insulin (5.13 [1.54-17.06]). No significant differences were seen in the other evaluated variables. Conclusion: This study found several factors associated with hypoglycemia during hyperglycemic crises treatment, many of which are not addressed in consensus statement recommendations. These findings may help ICU clinicians prevent complications related to hyperglycemic crisis management and generate hypotheses for future studies.

Coronavirus Disease 2019-Related Extensive Thrombosis in a Patient Receiving Therapeutic Anticoagulation With Dabigatran.

Introduction and Objective: Coronavirus disease 2019 (COVID-19) is associated with respiratory failure and a hypercoagulable state. Studies have shown the use of oral anticoagulants, specifically dabigatran, can significantly decrease mortality from COVID-19. Dabigatran is an oral direct thrombin inhibitor commonly used for nonvalvular atrial fibrillation and for the treatment or prevention of venous thromboembolism. The association of COVID-19-related extensive thrombosis while receiving full therapeutic anticoagulation with dabigatran has not been well-established in current literature. Case Report: We present a 73-year-old male patient with a history of persistent atrial fibrillation anticoagulated with dabigatran presenting with an active COVID-19 infection admitted to the intensive care unit. On hospital day 7, he developed extensive arterial and venous thromboembolisms. To our knowledge, this is the first published case of COVID-19-related extensive thrombosis while receiving full therapeutic anticoagulation with dabigatran. Discussion: Guidelines recommend prophylactic or therapeutic-dose anticoagulation with unfractionated heparin or low-molecular weight heparin for all patients if no contraindications exist; however, recommendations for the use of therapeutic oral anticoagulants have not been well established. Further studies are warranted to establish appropriate use of oral anticoagulants in the setting of COVID-19. Conclusion: Evidence from this report suggests clinicians should closely monitor patients at risk for hypercoagulability regardless of the anticoagulation therapy the patient may be receiving. Additionally, evidence from this case suggests a possible inferiority in the anticoagulation ability of dabigatran in patients with active COVID-19.

The role of bariatric and metabolic surgery in the development, diagnosis, and treatment of endometrial cancer.

The obesity pandemic continues to contribute to a worsening burden of disease worldwide. The link between obesity and diseases such as diabetes, cardiovascular disease, and cancer has been well established, yet most patients living with obesity remain untreated or undertreated. Metabolic and bariatric surgery is the most effective and durable treatment for obesity, is safe, and may have a protective benefit with respect to cancer incidence. In this review, an overview of the link between obesity, metabolic surgery, and cancer is discussed with emphasis on indications for endometrial cancer, the malignancy most strongly associated with obesity. Considerable evidence from retrospective and prospective cohort studies supports a decreased risk of endometrial cancer in patients with obesity who undergo bariatric surgery compared with nonsurgical controls. Survivors of endometrial cancer are at increased risk of poor health outcomes associated with obesity, and women with endometrial cancer are more likely to die of cardiovascular disease and other obesity-related illnesses than of the malignancy itself. Recent advances in anticancer drug therapies have targeted pathways that may also be therapeutically altered with metabolic surgery. Metabolic surgery has significant potential to enter the treatment paradigm for endometrial cancer, and gynecologic oncologist visits present an opportunity to identify patients who may benefit the most.

Comparison of Adverse Events With Vancomycin Diluted in Normal Saline vs Dextrose 5.

BACKGROUND: IV vancomycin is widely used for infections caused by Gram-positive bacteria; however, nephrotoxicity is commonly associated with its use. Clinical trials have shown an increased incidence of acute kidney injury (AKI) using normal saline (NS) for fluid resuscitation. This study evaluated differences in AKI and other patient outcomes associated with vancomycin diluted in NS compared with dextrose 5% in water (D5W). METHODS: This retrospective cohort study conducted at a single US Department of Veterans Affairs hospital included veterans who received vancomycin for at least 48 hours between July 1, 2015 and June 30, 2020. This study compared adverse events (AEs) of patients receiving vancomycin diluted in either NS or D5W. The primary outcome was incidence of AKI. Secondary outcomes included incidence of hyperglycemia, hyperchloremia, hypernatremia, metabolic acidosis, in-hospital mortality, and 30-day posthospitalization mortality. RESULTS: The study included 123 patients in each group (N = 246). The percentage of AKI was 22.8% in the D5W group compared with 14.6% the NS group (P = .14). There were no significant differences in the rates of hyperglycemia, hyperchloremia, hypernatremia, or metabolic acidosis between the 2 groups. In-hospital mortality and 30-day posthospitalization mortality were similar between the groups. CONCLUSIONS: This study comparing the AEs of IV vancomycin diluted in NS and D5W found no significant differences in AKI or other patient outcomes. These study results do not suggest the crystalloid used to dilute IV vancomycin is associated with differences in nephrotoxicity or other relevant AEs.

A Comparison Between Cefepime and Piperacillin-Tazobactam in the Management of Septic Shock.

Introduction Septic shock is defined as a dysregulated host response to infection characterized by hemodynamic instability. Concern for the increased risk of acute kidney injury (AKI) with piperacillin-tazobactam in combination with vancomycin may prompt more use of alternative broad-spectrum antipseudomonal beta-lactam antibiotics, such as cefepime. This study assessed whether cefepime was associated with improved outcomes compared to piperacillin-tazobactam in patients with septic shock. Methods This retrospective cohort study included veterans treated for septic shock between September 1, 2008, and August 31, 2018. This study compared cefepime and piperacillin-tazobactam as initial antibiotic management for septic shock. Outcomes included AKI, Clostridioides difficile infection (CDI), hospital length of stay, intensive care unit mortality, and mortality within 30 days of hospitalization. Results In total, 240 patients were included in this study (120 in each cohort). The proportion of AKI was 60.0% in the piperacillin-tazobactam cohort compared to 58.3% in the cefepime cohort (p = 0.90). Mortality was significantly higher in the cefepime cohort. There were no significant differences in CDI or hospital length of stay. Conclusion The results of this study do not suggest that the use of the antipseudomonal beta-lactam antibiotic used in the initial management of septic shock is associated with differences in the AKI or CDI. The higher mortality observed with cefepime may warrant further investigation.

Gender disparities in academic rank achievement in neurosurgery: a critical assessment.

OBJECTIVE: The objective of this study was to evaluate whether there are disparities in academic rank and promotion between men and women neurosurgeons. METHODS: The profiles of faculty members from 50 academic neurosurgery programs were reviewed to identify years in practice, number of PubMed-indexed publications, Doctor of Philosophy (PhD) attainment, and academic rank. The number of publications at each academic rank was compared between men and women after controlling for years in practice by using a negative binomial regression model. The relationship between gender and each academic rank was also determined after controlling for clustering at the institutional level, years in practice, and number of publications. RESULTS: Of 841 faculty members identified, 761 (90%) were men (p = 0.0001). Women represented 12% of the assistant and associate professors but only 4% of the full professors. Men and women did not differ in terms of the percentage holding a PhD, years in practice, or number of publications at any academic rank. After controlling for years in practice and clustering at the facility level, the authors found that men were twice as likely as women to be named full professor (OR 2.2, 95% CI 1.09-4.44, p = 0.03). However, when institution, years in practice, PhD attainment, h-index, and number of publications were considered, men and women were equally likely to attain full professorship (OR 0.9, 95% CI 0.42-1.93). CONCLUSIONS: Data analysis of the top neurosurgery programs suggests that although there are fewer women than men holding positions in academic neurosurgery, faculty rank attainment does not seem to be influenced by gender.

When Hurt Heroes Do Harm: Collective Guilt and Leniency toward War-Veteran Defendants with PTSD.

Veterans with post-traumatic stress disorder (PTSD) are at heightened risk for interfacing with the United States legal system as criminal defendants. Two experiments were used to test the hypothesis that American mock jurors would punish a veteran (vs. a civilian) with PTSD for a violent crime less harshly because of their own collective guilt (i.e., the guilt felt for the transgressions of one's in-group) about the veteran's suffering due to war. The participants were United States citizens recruited online (n = 174) who completed a mock-juror experiment involving a violent assault committed by either a veteran or a civilian with PTSD. As predicted, jurors were more lenient toward the veteran (vs. the civilian). For male mock jurors this was explained by their collective guilt for the veteran's war-related suffering. A second study experimentally induced individual and collective guilt about veteran defendants, finding that mock jurors (n = 533) who are less likely to share a salient in-group identity with the veteran (i.e., women, people with lower national identification with the United States) can be induced to feel the requisite guilt to exhibit leniency toward a veteran. Thus, veterans suffering from PTSD may receive more lenient punishment because they elicit a sense of collective guilt in legal decision-makers.