The association between leptin and weight maintenance outcome in anorexia nervosa.

OBJECTIVE: Relapse after weight restoration in anorexia nervosa (AN) is a critical problem. Higher body fat percentage after weight gain has been shown to predict better weight maintenance outcome. Leptin, a fat-derived hormone, has been associated with progress during weight gain, but its association with weight maintenance is unknown. This study aims to determine whether leptin levels after weight restoration in AN are associated with weight maintenance. METHOD: Participants were 41 women with AN hospitalized for inpatient treatment. Participants were evaluated 2-4 weeks after weight restoration to body mass index (BMI) ≥ 19.5 kg/m2 for plasma leptin and body composition. Weight maintenance outcome was defined by whether a participant maintained a BMI of at least 18.5 kg/m2 at the end of 1 year following hospital discharge. RESULTS: Twenty (48.8%) out of 41 patients maintained their weight at 1 year. Percent body fat and leptin were significantly higher in the group who maintained weight (body fat, p = .004, Hedges' g = 0.944; log-leptin, p = .010, Hedges' g = 0.821), but there were no differences in predischarge BMI, duration of illness, and duration of amenorrhea. Using regression modeling, only higher log-leptin (pWald = .021) and percent body fat (pWald = .010), as well as fat-adjusted leptin (pWald = .029), independently predicted weight maintenance at 1 year. DISCUSSIONS: Our findings suggest that for acutely-weight restored women with AN, higher predischarge leptin measurements are associated with better outcome in the year following treatment. Prospective studies examining leptin as well as other parameters of metabolic health could offer insights into biomarkers that may improve clinical outcomes.

Phase I Study of Trifluridine/Tipiracil Plus Irinotecan and Bevacizumab in Advanced Gastrointestinal Tumors.

PURPOSE: This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Dose escalation (3+3 design) in advanced gastrointestinal tumors was followed by expansion in mCRC. During dose escalation, patients received FTD/TPI (20-35 mg/m2 twice daily; days 1-5 of a 14-day cycle) and irinotecan (120-180 mg/m2; day 1). During expansion, the MTD of FTD/TPI and irinotecan plus bevacizumab (5 mg/kg; day 1) was administered. RESULTS: Fifty patients (26 across six dose-escalation cohorts and 24 in the expansion phase) were enrolled. Two dose-limiting toxicities (fatigue and neutropenia) were observed in the dose-escalation phase, and MTD was defined as FTD/TPI 25 mg/m2 twice daily plus irinotecan 180 mg/m2. In the expansion phase, 83% (20/24) experienced any-cause grade ≥3 adverse events (AEs) with the triplet combination, most frequently neutropenia (42%), leukopenia (25%), and diarrhea (12%). AEs of any-cause led to dosing interruptions, modifications, and discontinuations in 29%, 17%, and 4% of patients, respectively. No treatment-related deaths occurred. Three patients (12%) experienced partial responses and 16 (67%) patients had stable disease lasting >4 months. The median progression-free survival was 7.9 months (95% confidence interval, 5.1-13.4 months). CONCLUSIONS: Tolerability and activity observed in this phase I trial support further investigation of the FTD/TPI-irinotecan-bevacizumab combination in previously treated mCRC.

Systemic Chemotherapy for Metastatic Colitis-Associated Cancer Has a Worse Outcome Than Sporadic Colorectal Cancer: Matched Case Cohort Analysis.

BACKGROUND: Colitis-associated cancers (CAC) are a catastrophic complication of inflammatory bowel disease; at diagnosis, CAC is frequently at an advanced stage. Although the genomic alterations (GA) in CAC are different from sporadic colorectal cancer (CRC), the same systemic therapies are used. We compared clinically relevant outcomes using standard care systemic chemotherapy of stage IV CAC versus a matched patient control cohort of stage IV CRC patients. PATIENTS AND METHODS: A retrospective matched cohort design was used. Eighteen cases of stage IV CAC (7 ulcerative colitis, 11 Crohn disease) and 18 CRC were identified. GA analysis was available for all patients. Outcome endpoints included response rate and response duration, progression-free survival, and OS. RESULTS: Although the response rates were similar (CAC 35.7% vs. CRC 57.1%, P = .45), the median duration of response for CAC was significantly shorter (1.4 months, vs. CRC 11.8 months, P = .006). There was no difference in dose density of first-line therapy between cohorts, suggesting that shorter response duration was due to more rapid development of chemotherapy resistance. Median OS was significantly shorter for CAC patients (13 vs. 27.6 months, P = .034). As expected, there was a difference in the spectrum of GA between CAC and CRC cohorts. However, GA associated with poor prognosis (eg, B-Raf) were no more frequent in the CAC cohort. CONCLUSION: Clinically meaningful outcomes of duration of response and OS are worse for CAC versus sporadic CRC patients treated with FOLFOX or FOLFIRI as first therapy for metastatic disease.

Posterior instability of the shoulder following thermal capsulorrhaphy for multidirectional instability.

Patients with multidirectional instability (MDI) of the shoulder can be treated with arthroscopic thermal capsulorrhaphy. However, recent literature suggests that complications and failures associated with this technique are on the rise. We present the case of a 30-year-old female patient who was treated for a failed thermal capsulorrhaphy. She had undergone this treatment of her left shoulder for MDI but had persistent pain with overhead activities and clicking in the posterior shoulder. Her history and physical examination were consistent with persistent posterior unidirectional instability of the shoulder. Magnetic resonance imaging showed a possible separation of the capsule from the posterior glenoid. After conservative management had been attempted several times, an arthroscopic repair was performed. At surgery, the anterior and inferior capsule appeared to be tight. However, the posterior capsule was extremely lax and patulous, but intact. A posterior capsule plication was performed arthroscopically, along with a rotator interval closure. Postoperatively, the patient was maintained in a sling that kept the arm in neutral rotation. At 6 weeks, the sling was removed, and a slow, progressive program of therapy was initiated. Stress on the posterior capsule was not permitted for 3 months. At 1-year follow-up, the patient had full pain-free range of motion and returned to participation in sports without limitation.

Corrective supracondylar humeral osteotomies using the small AO external fixator.

Traditional methods of correcting malunited distal humeral fractures in children involve complex wedge osteotomies held with pins or internal fixation devices. These require a large exposure and challenging fixation. We elected to perform simple transverse osteotomies, without wedges, using a lateral incision. These were maintained by the small AO external fixator. Between 1987 and 2004, five children with malunited distal humeral fractures were treated. Angular and rotational correction was obtained in each case. Bony union occurred at an average of 8 weeks. A simple osteotomy held by the small AO external fixator provides accurate correction, precise adjustability, and solid stability.