A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity.

Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6 kg (95% CI: -2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was well-tolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits.

Minimally Invasive Surgical Decompression without Fusion for the Treatment of Lumbar Synovial Cysts: Feasibility and Long-Term Outcomes.

BACKGROUND: Lumbar synovial cysts (LSCs) can cause painful radiculopathy and sensory and/or motor deficits. Historically, first-line surgical treatment has been decompression with fusion. Recently, minimally invasive laminectomy without fusion has shown equal or superior results to traditional decompression and fusion methods. OBJECTIVE: This study investigates the long-term efficacy of minimally invasive laminectomy without fusion in the treatment of LSC as it relates to the rate of subsequent fusion surgery. METHODS: A retrospective review was performed over a 10-year period of patients undergoing minimally invasive laminectomy for symptomatic LSCs. The primary end point was the rate of revision surgery requiring fusion. RESULTS: Eighty-five patients with symptomatic LSCs underwent minimally invasive laminectomy alone January 2010-August 2020 at our institution. The most common location was L4-5 (72%). Preoperative imaging identified spondylolisthesis (grade 1) in 43 patients (57%), none of which was unstable on available dynamic radiographs. Average procedure duration was 93 minutes, with 78% of patients discharged home on the same day of surgery. Over 46 months of mean follow-up, 17 patients (20%) required 19 revision operations. Of those operations, 16 were spinal fusions (17.6%). Median time to fusion surgery was 36 months. There were no identifiable risk factors on multivariate regression analysis that predicted the need for fusion. CONCLUSIONS: Minimally invasive laminectomy is an effective first-line treatment for symptomatic LSCs and avoids the need for fusion in most treated patients. Of our patients, 18% required a fusion over 46 months, suggesting that further studies are required to guide patient selection.

An Evidence-Based Approach to Multi-Ligamentous Knee Injuries.

Multi ligament knee injuries (MLKIs) are highly complex injuries with associated complications and often present with difficult management strategies. MLKIs may affect the anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), medial collateral ligament (or posteromedial corner (PMC)), and lateral collateral ligament (or posterolateral corner (PLC)) in addition to other structures including the menisci, common peroneal nerve, and popliteal artery. MLKIs are highly associated with the male sex and are commonly seen in high-velocity motor vehicle accidents and low-velocity sports injuries. Given the multiple planes of movement in the knee and various primary and secondary stabilizers throughout those planes, there is great heterogeneity in an injury pattern and most involve the ACL and PCL. Initial evaluation of this injury includes assessment of lower extremity sensation, distal pulses, and ankle-brachial index (ABI). If vascular compromise is suspected, computed tomography angiography (CTA) or magnetic resonance angiography (MRA) are indicated to evaluate the vasculature. As opposed to CTA, MRA offers visualization of the soft-tissue structures that are commonly damaged in MLKIs. Initial management typically includes closed reduction of the knee with subsequent external fixation. Classification systems guide initial assessments; however, further management is unclear and leads the surgical team to decide the best, individualized management option for each patient. As a result, optimal surgical and postoperative treatment options remain complicated, and clinical outcomes remain difficult to predict. The purpose of this review is to consolidate the most up-to-date practices of the diagnostic workup, management, and treatment of MLKIs.

Current Trends in IBD-Development of Mucosal-Based Biomarkers and a Novel Minimally Invasive Recoverable Sampling System.

Despite recent developments in therapy for inflammatory bowel diseases (IBDs), there have been limited advances in diagnostic tools available to aid in disease management. A growing body of evidence suggests that there are important host-microbe interactions at the mucosal interface that modulate the inflammatory response in patients with IBD. Additionally, the importance of mucosal integrity and its disruption appears to be important in the pathophysiology and perpetuation of the disease. The ability to characterize this interface may provide valuable information for both disease monitoring and identification of new treatment targets. Endoscopy remains the primary tool for disease monitoring, and mucosal healing is the primary therapeutic target in IBD treatment. However, establishing mucosal healing requires repetitive endoscopic procedures, and endoscopy is limited by factors such as invasiveness, cost, and risk of adverse events. Moreover, the use of a bowel preparation for colonoscopies alters the mucus layer and thus perturbs evaluation of the host-microbe interaction. Stool sampling may also be inaccurate because it reflects the end state of metabolites and proteins, failing to take into account the degradation or alteration of substrates of interest by bacterial proteases and other enzymes during passage through the colon. A novel sampling capsule, called the Recoverable Sampling System (RSS), is being developed as a complementary tool to colonoscopy. The RSS is intended to be a platform for noninvasive autonomous sampling, preservation, handling, and storage of analytes of interest found in the gastrointestinal fluids. A proprietary preservative contained within the chambers of the capsule has been developed to stabilize DNA and proteins for ex vivo microbiome and metabolomics analyses. Surrogate markers such as SPP24 and GUCA2a have been identified to correlate with gut health, intestinal permeability, and inflammation and could be locally sampled by the RSS. The potential clinical utility of an RSS device is broad and would likely be able to guide therapy by allowing for more frequent disease monitoring, aiding in disease characterization, and facilitating in the identification of novel therapeutic targets.

A new technology is being developed, Recoverable Sampling System (RSS), that may allow sampling without a colonoscopy. This may lead to new biomarkers and even drug targets which may ultimately improve the care of these patients.