Objective: To describe the distribution of femoral neck shortening after internal fixation and to determine whether shortening is associated with inferior hip function at 24 months after a hip fracture in patients 50 years of age or older. Design: Retrospective cohort study. Setting: A secondary analysis of data from 81 clinical centers included in the Fixation using Alternative Implants for the Treatment of Hip Fractures (FAITH) trial. Participants: Three hundred fifty patients, 50 years of age or older, who had an isolated femoral neck fracture and underwent timely operative fixation of the fracture. Intervention: Femoral neck shortening was measured as a categorical variable and classified into one of the following groups, as determined by the Central Adjudication Committee: no shortening, mild shortening (≤5 mm), moderate shortening (6–10 mm), or severe shortening (>10 mm). Main Outcome Measurement: The primary outcome for the current analysis was hip function, as measured by the Western Ontario & McMaster Universities Osteoarthritis Index questionnaire, at 24 months after injury. Results: Two-thirds of patients had no or mild shortening (≤5 mm), whereas one-third of patients had moderate or severe shortening (>5 mm). After adjusting for surgical treatment, a greater amount of femoral neck shortening was found to be associated with poorer hip function (P < 0.01). Conclusions: We found that increasing femoral neck shortening was associated with inferior hip function. Although internal fixation often results in successful union, patients who heal in a shortened position report poorer functional outcomes. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.
PFDs are prevalent in gynecologic cancer survivors and this is an important area of clinical concern and future research.
Postoperative bleeding occurs in 1.5% of patients undergoing a LRYGB and is associated with significantly increased morbidity and mortality. We have identified patient and operative factors that are independently associated with postoperative bleeding.
Fibroblast growth factor-19 (human FGF19; murine FGF15) suppresses bile acid synthesis. In FGF19 deficiency, diarrhea resulting from bile acid spillage into the colon mimics irritable bowel syndrome. To seek other consequences of FGF19/15 deficiency, we used Fgf15-/- and wild-type (WT) mice to assess gallbladder filling, the bile acid pool, fecal bile acid levels, and colon neoplasia. We fasted mice for six hours before assessing gallbladder size by magnetic resonance imaging (MRI). We measured bile acid levels in different compartments by enzymatic assay, and induced colon neoplasia with azoxymethane (AOM)/dextran sodium sulfate (DSS) and quantified epithelial Ki67 immunostaining and colon tumors 20 weeks later. In vivo MRI confirmed the gross finding of tubular gallbladders in FGF15-deficient compared to WT mice, but fasting gallbladder volumes overlapped. After gavage with a bile acid analogue, ex vivo MRI revealed diminished gallbladder filling in FGF15-deficient mice (P = 0.0399). In FGF15-deficient mice, the total bile acid pool was expanded 45% (P <0.05) and fecal bile acid levels were increased 2.26-fold (P <0.001). After AOM/DSS treatment, colons from FGF15-deficient mice had more epithelial cell Ki67 staining and tumors (7.33 ± 1.32 vs. 4.57 ± 0.72 tumors/mouse; P = 0.003 compared to WT mice); carcinomas were more common in FGF15-deficient mice (P = 0.01). These findings confirm FGF15, the murine homolog of FGF19, plays a key role in modulating gallbladder filling and bile acid homeostasis. In a well-characterized animal model of colon cancer, increased fecal bile acid levels in FGF15-deficient mice promoted epithelial proliferation and advanced neoplasia.
Background: Expression and activation of subtype-3 muscarinic receptors (M3R) plays an important role in the progression of colorectal neoplasia. Methods: Herein, we describe the role of muscarinic receptors in colon cancer, focusing specifically on M3R, illustrate how M3R over-expression and activation of post - receptor signaling pathways potentiates tumor progression, and explore the efficacy and safety of a variety of therapeutic approaches that can target the molecules involved. Results: Colon cancers overexpress M3R mRNA (CHRM3) and protein, and post-M3R signaling stimulates cell proliferation. Post-M3R signal transduction is complex, involving interplay between epidermal growth factor receptors (EGFR)/ERK and protein kinase C (PKC)/p38 mitogen-activated protein (MAP) kinase signaling pathways. In particular, the development of an invasive and metastatic phenotype requires that these signaling interactions augment cellular release of a key collagenase, matrix metalloproteinase-1 (MMP1). Blocking either M3R activation or post-M3R signaling attenuates MMP1 release and colon cancer invasiveness. Conclusions: Parsing the complexities of these signaling interactions is important, not only to understand these mechanisms of cancer initiation and progression, but also to develop novel treatment modalities. Since the vast majority of persons with colon cancer die from disseminated disease, preventing or reversing metastatic spread of cancer cells by targeting M3R, post-M3R signaling, or MMP1 has therapeutic potential.
Our work has focused on defining the utility of fluorine (19F)-labeled bile acid analogues and magnetic resonance imaging (MRI) to identify altered bile acid transport in vivo. In the current study, we explored the ability of this approach to differentiate fibroblast growth factor-15 (FGF15)- deficient from wild-type (WT) mice, a potential diagnostic test for bile acid diarrhea, a commonly misdiagnosed disorder. FGF15 is the murine homologue of human FGF19, an intestinal hormone whose deficiency is an underappreciated cause of bile acid diarrhea. In a pilot and three subsequent pharmacokinetic studies, we treated mice with two 19F-labeled bile acid analogues, CA-lys-TFA and CA-sar-TFMA. After oral dosing, we quantified 9F-labeled bile acid analogue levels in the gallbladder, liver, small and large intestine, and plasma using liquid chromatography mass spectrometry (LC-MS/MS). Both 19F bile acid analogues concentrated in the gallbladders of FGF15-deficient and WT mice, attaining peak concentrations at approximately 8.5 h after oral dosing. However, analogue levels in gallbladders of FGF15-deficient mice were several-fold less compared to those in WT mice. Live-animal 19F MRI provided agreement with our LC-MS/MS-based measures; we detected robust CA-lys-TFA 19F signals in gallbladders of WT mice but no signals in FGF15-deficient mice. Our finding that 19F MRI differentiates FGF15-deficient from WT mice provides additional proof-of-concept for the development of 19F bile acid analogues and 19F MRI as a clinical test to diagnose bile acid diarrhea due to FGF19 deficiency and other disorders.
Background In 2017, the Accreditation Council for Graduate Medical Education program guidelines changed to include a section that requires programs to optimize resident and faculty member well-being. There is still a poor understanding of general surgery resident wellness, and there are few well-established wellness programs. Methods We created a novel 50-question anonymous survey to assess burnout, depression, and wellness that was distributed to the general surgery residents as part of a pilot study. Univariate analysis was performed to assess wellness and wellness changes. Bivariate analysis was performed to determine the association between wellness variables and gender, age, and postgraduate year (PGY) level. Results Thirty-five of 55 residents participated in the survey. Over half of the residents (54%) reported gaining weight during residency. Nearly 70% reported working while having an ongoing family issue, and 77% worked at least once while ill. Fourteen residents (40%) reported that their wellness worsened over the previous academic year, while 7 (20%) reported that it remained the same, and 11 (31%) reported that it improved. These changes varied significantly by the PGY level ( P < .01). Age (younger vs older than 30) and sex were found to be effective measure modifiers of the association between wellness change and PGY level. Discussion The overall wellness of the general surgery residents at our institution varies greatly. Poor wellness may lead to inferior patient care, burnout and depression, and negative resident morale. Residency programs need to implement programming to address wellness deficiencies.
Background and Objectives:Staple line treatment during laparoscopic sleeve gastrectomy (LSG) remains a controversial issue among bariatric surgeons. The objective of this study was to compare rates of postoperative bleeding (POB) among various methods of staple line reinforcement.Methods:The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program 2015 dataset was queried for patients undergoing an LSG. Patients were stratified by staple line treatment groups—no treatment (NT), suture oversewing (OVERSEW), buttressing by a commercial product (BUTTRESS), and both buttress and oversew (COMBINATION). The primary outcome was POB. Multivariable logistic regression was used to compare POB rates among the treatment groups.Results:In the 98,142 LSG patients meeting selection criteria, 623 (0.63%) patients had POB and 181 (0.18%) required reoperation. POB occurred in 0.80% for the NT group, 0.68% for the OVERSEW group, 0.57% for the BUTTRESS group, and 0.55% for the COMBINATION group. On multivariable analyses, all treatment groups were less likely to have POB compared with the NT group—OVERSEW (odds ratio [OR] 0.73, 95% confidence interval [CI] 0.54–0.98), BUTTRESS (OR 0.70, 95% CI 0.57–0.84), and COMBINATION (OR 0.66, 95% CI 0.50–0.89) (all P < .01). Subset analysis revealed no difference between BUTTRESS and OVERSEW (OR 0.95, 95% CI 0.71–1.26, P = .71).Conclusions:Relative to an NT staple line, the use of OVERSEW or BUTTRESS can decrease the rates of POB by up to 30%. The use of these techniques should be strongly considered by the bariatric surgeon.
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