Palliative procedures for malignant gastric outlet obstruction: a network meta-analysis.

BACKGROUND: The optimal treatment for malignant gastric outlet obstruction (GOO) remains uncertain. This systematic review aimed to comprehensively investigate the efficacy and safety of four palliative treatments for malignant GOO: gastrojejunostomy, endoscopic ultrasound-guided gastroenterostomy (EUS-GE), stomach-partitioning gastrojejunostomy (PGJ), and endoscopic stenting. METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform for randomized controlled trials (RCTs) and cohort studies comparing the four treatments for malignant GOO. We included studies that reported at least one of the following clinical outcomes: clinical success, 30-day mortality, reintervention rate, or length of hospital stay. Evidence from RCTs and non-RCTs was naïve combined to perform network meta-analysis through the frequentist approach using an inverse variance model. Treatments were ranked by P score. RESULTS: This network meta-analysis included 3617 patients from 4 RCTs, 4 prospective cohort studies, and 32 retrospective cohort studies. PGJ was the optimal approach in terms of clinical success and reintervention (P scores: 0.95 and 0.90, respectively). EUS-GE had the highest probability of being the optimal treatment in terms of 30-day mortality and complications (P scores: 0.82 and 0.99, respectively). Cluster ranking to combine the P scores for 30-day mortality and reintervention indicated the benefits of PGJ and EUS-GE (cophenetic correlation coefficient: 0.94; PGJ and EUS-GE were in the same cluster). CONCLUSION: PGJ and EUS-GE are recommended for malignant GOO. PGJ could be the alternative choice in centers with limited resources or in patients who are unsuitable for EUS-GE.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials of the Effects of Vitamin D Supplementation on Children and Young Adults with HIV Infection.

BACKGROUND: Children and young adults with HIV infection may exhibit vitamin D deficiency, which is harmful to bone health as well as the endocrine and immune systems. OBJECTIVES: This study sought to investigate the effect of vitamin D supplementation on children and young adults with HIV infection. METHODS: The PubMed, Embase, and Cochrane databases were searched. Randomized controlled trials that have evaluated the effects of vitamin D supplementation (ergocalciferol or cholecalciferol) at any dose or for any duration in children and young adults with HIV infection, aged 0-25 y, were included. A random-effects model was used, and the standardized mean difference (SMD) and 95% CI were calculated. RESULTS: Ten trials, with 21 publications and 966 participants (mean age: 17.9 y), were included in the meta-analysis. The supplementation dose and the duration of the studies included ranged from 400 to 7000 IU/d and from 6 to 24 mo, respectively. Vitamin D supplementation was associated with a significantly higher serum 25(OH)D concentration at 12 mo (SMD: 1.14; 95% CI: 0.64, 1.65; P < 0.00001) compared with a placebo. No significant difference was observed in spine BMD (SMD: -0.09; 95% CI: -0.47, 0.3; P = 0.65) at 12 mo between these 2 groups. However, participants who received higher doses (1600-4000 IU/d) had significantly higher total BMD (SMD: 0.23; 95% CI: 0.02, 0.44; P = 0.03) and nonsignificantly higher spine BMD (SMD: 0.3; 95% CI: -0.02, 0.61; P = 0.07) at 12 mo compared with those who received standard doses (400-800 IU/d). CONCLUSIONS: Vitamin D supplementation in children and young adults with HIV infection increases the serum 25(OH)D concentration. A relatively high daily dose of vitamin D (1600-4000 IU) improves total BMD at 12 mo and results in sufficient 25(OH)D concentrations.

A review of the extraction methods and advanced applications of lignin-silica hybrids derived from natural sources.

The global trend of increasing energy demand along the large volume of wastewater generated annually from the paper pulping and cellulose production industries are considered as serious dilemma that may need to be solved within these current decades. Within this discipline, lignin, silica or lignin-silica hybrids attained from biomass material have been considered as prospective candidates for the synthesis of advanced materials. In this study, the roles and linking mechanism between lignin and silica in plants were studied and evaluated. The effects of the extraction method on the quality of the obtained material were summarized to show that depending on the biomass feedstocks, different retrieval processes should be considered. The combination of alkaline treatment and acidic pH adjustment is proposed as an effective method to recover lignin-silica with high applicability for various types of raw materials. From considerations of the advanced applications of lignin and silica materials in environmental remediation, electronic devices and rubber fillers future valorizations hold potential in conductive materials and electrochemistry. Along with further studies, this research could not only contribute to the development of zero-waste manufacturing processes but also propose a solution for the fully exploiting of by-products from agricultural production.

The shrinking toe sign in gout.

OBJECTIVE: To describe the frequency, clinical presentation and understand the pathophysiology of toe shortenings during urate-lowering treatment (ULT) of gout, a feature we called the shrinking toe sign. METHODS: Sequential foot photographs and radiographs of 1141 consecutive gouty patients followed-up for at least 6 months under ULT were retrospectively scrutinized. Features from patients with toe shortenings were extracted from anonymized files. Tophi adjacent to the shortening sites were semi quantified on foot photographs and toe shortenings were measured on radiographs with the Corel draw software (Corel corporation, Canada). Measurement concordance was assessed by concordance correlation coefficients (CCC) and correlation between tophus scores and toe shortenings was analyzed by using linear model with a patient random effect. 97 patients who did not develop toe shortening during ULT were analyzed as controls. RESULTS: Shrinking toes were observed in 10 patients (0.9%) with tophaceous gout at joints with baseline destructive arthropathy. The first and second toes and metatarsophalangeal joints were predominantly involved. The sign was observed after serum urate had been lowered below the 300 and 360 µmol/l targets, in 8 and 2 patients, respectively. Measured shortenings (CCC: 0.99) correlated (p < 10-4) with decreases in tophus score (CCC: 0.91). Sequential radiograph analysis revealed that toe shortening was mainly due to lytic bone collapse during articular tophus dissolution. Comparison with controls showed that the sign developed in severe gout and in joints with more severe erosion score at baseline. CONCLUSION: The shrinking toe appears as rare feature of severe tophaceous gout, triggered by dissolution of bone-replacing tophi. Our findings reinforce the need to treat gout early, before destruction of bone scaffold by extensive tophi, as MSU crystal dissolution by ULT may further weaken these areas and induce their collapse.

Characteristics of polycyclic aromatic hydrocarbons in ambient air of a tropical mega-area, Ho Chi Minh City, Vietnam: concentration, distribution, gas/particle partitioning, potential sources and cancer risk assessment.

This is the first investigation on overall characteristics of 25 polycyclic aromatic hydrocarbons (PAHs) (15 PAHs regulated by US-EPA (excluding naphthalene) and 16 PAHs recommended by the European Union) in ambient air of Ho Chi Minh City, Vietnam. Their levels, congener profiles, gas/particle partitioning, potential sources of atmospheric PAHs (gas and particulate phases), and lung cancer risks in the dry and rainy seasons were examined. The ∑25 PAH concentration in the dry and rainy seasons ranged from 8.79 to 33.2 ng m-3 and 26.0 to 60.0 ng m-3, respectively. Phenanthrene and Indeno[123-cd]pyrene were major contributors to gaseous and particulate PAHs, respectively, while benzo[c]fluorene was dominant component of the total BaP-TEQ. The ∑16 EU-PAH concentration contributed to 13 ± 2.7% of the total ∑ 25 PAH concentration; however, they composed over 99% of the total ∑ 25 PAH toxic concentration. Adsorption mainly governed the phase partitioning of PAHs because the slope of correlation between logKp and logP0L was steeper than - 1. Vehicular emission was the primary source of PAHs in two seasons; however, PAHs in the dry season were also originated from biomass burning. Assessment of lung cancer risk showed that children possibly exposed to potential lung cancer risk via inhalation.

Identification and Characterization of Epivascular Glia Using En Face Optical Coherence Tomography.

PURPOSE: The purpose of this study was to describe the clinical features of epivascular glia (EVG) using en face optical coherence tomography (OCT). DESIGN: Retrospective cross-sectional study. METHODS: Single-institution en face OCT images were reviewed. Eyes displaying EVG were captured with manual internal limiting membrane (ILM) segmentation and analyzed with customized segmentation . A random age- and sex-matched control group was selected to determine relative epiretinal membrane (ERM) prevalence. RESULTS: Characteristic hyper-reflective ILM plaques with dendrite-like radiations were identified using en face OCT and displayed vascular predilection. A total of 161 eyes with EVG (the EVG group) and 2,315 eyes without EVG (control group) were identified from a total cohort of 1,298 patients (or 2,476 eyes). The prevalence of EVG was 161 of 2,476 eyes (6.5%) and 119 of 1,298 patients (9.2%) in the cohort. Mean age was 79.3 ± 10.7 years old in the EVG group and 55.9 ± 24.6 years old in the control group (P <.001). An advanced posterior vitreous detachment (PVD) stage was more common in the EVG group (grade 3: 41.7%; grade 4: 48.6%) than in the control group (grade 3: 18.5%; grade 4: 26.9%; P <.001). Contractile ERM was present in 71 of 161 eyes (44.1%) with EVG compared to 30 of 161 eyes (18.6%) in a random age- and sex-matched control cohort without EVG (P <.001). CONCLUSIONS: EVG previously described with histopathology and scanning electron microscopy can be identified using en face OCT. In this study, these lesions were associated with older age, pseudophakia, and advanced PVD, supporting the role of Müller cell activation through ILM breaks triggered by PVD, a pathogenic mechanism proposed by previous studies.

Hyperreflective Stress Lines and Macular Holes.

Purpose: To determine the prevalence of a central hyperreflective line in eyes with full-thickness macular holes (FTMH) and lamellar macular holes (LMH) and to elucidate the pathoanatomic importance of this optical coherence tomography (OCT) sign. Methods: This retrospective analysis evaluated patients with FTMH and LMH at the Stein Eye Institute. Clinical data was collected and SD-OCT volume scans were analyzed for the presence of a central vertical hyperreflective line in 3 separate cohorts: patients with SD-OCT preceding FTMH development, patients with SD-OCT after pars plana vitrectomy (PPVT) treatment for FTMH, and patients with SD-OCT of LMH. Results: In total, 93 eyes with FTMH and 88 eyes with LMH were identified. Of the 93 FTMH eyes, SD-OCT volume scans were available before development of the FTMH in 12 eyes. Of these, 6 (50%) displayed a vertical hyperreflective line preceding the development of the FTMH. Fifty-one eyes underwent PPVT with resolution of the FTMH, and 26 displayed a hyperreflective line after resolution (51%). Of the 88 eyes with LMH, 22 displayed a hyperreflective line (25%). All hyperreflective lines were noted at the central fovea. Conclusions: SD-OCT illustrated the presence of a central vertical hyperreflective line preceding FTMH and after resolution of FTMH after PPVT in approximately one-half of cases, and concurrent with LMH in 25% of cases. This vertical hyperreflective line may represent an early SD-OCT marker for the development of FTMH, and may be a sign of central foveal dehiscence owing to disruption of the Muller cell cone.

Inner choroidal ischaemia and CNV due to handheld laser-induced maculopathy: a case report and review.

There has been a sharp rise of reported handheld laser-induced maculopathy (HLIM) cases over the past decade, a concerning trend that may continue due to unregulated online access to high power lasers. Though HLIM has distinct clinical features, not uncommonly it may masquerade as other retinal disorders. It is critical therefore to recognise the clinical and multimodal imaging characteristics of this important and potentially devastating condition. As HLIM patients are typically young, unique issues need to be considered, such as delayed presentation, difficult history, poor compliance and behavioural or psychiatric comorbidity. This article will review the clinical and diagnostic features of laser injury, with a special emphasis on the multimodal retinal findings. In addition, we present a unique case of HLIM, resembling the presentation of a placoid disease variant and illustrating choroidal ischaemia using advanced retinal imaging, that offers further insight into the mechanisms of laser injury and its complications. The issues addressed in this review aim to increase recognition of an increasingly important and trending condition with potentially profound visual complications.

Pentosan-associated maculopathy: prevalence, screening guidelines, and spectrum of findings based on prospective multimodal analysis.

OBJECTIVE: To describe the prevalence and spectrum of multimodal imaging findings of pentosan polysulfate sodium (PPS)-associated maculopathy and to recommend dosage-related screening guidelines. DESIGN: Cross-sectional study. METHODS: Patients previously or currently treated with PPS at University of California, Los Angeles, were randomly ascertained and prospectively screened for PPS-associated maculopathy with multimodal retinal imaging. Daily and cumulative dosages of PPS exposure were calculated for each patient. Images were studied to identify the characteristic findings of toxicity. The prevalence of PPS-associated maculopathy and screening guidelines were determined. RESULTS: The prevalence of PPS-associated maculopathy in this cohort was 20% (10/50 patients). Both average duration of PPS therapy and average cumulative dosage were significantly lower in the unaffected (6.3 ± 6.6 years, 691.7 ± 706.6 g) versus the affected groups (20.3 ± 6.6 years, 3375.4 ± 1650.0 g, p < 0.001). Near-infrared reflectance (NIR) illustrated characteristic punctate retinal pigment epithelium (RPE) macular lesions early. Fundus autofluorescence (FAF) showed speckled autofluorescence in the posterior pole with peripapillary extension. Co-localization with optical coherence tomography (OCT) displayed focal RPE thickening and, in more severe cases, RPE atrophy in the macula and even the periphery. CONCLUSIONS: A prevalence of 20% in this study cohort suggests a significant risk of macular toxicity for PPS-treated patients. Characteristic alterations are best detected with FAF and NIR. More significant PPS exposure was associated with more severe atrophy. We recommend an initial baseline eye examination to include OCT and, most importantly, NIR and FAF with annual retinal imaging thereafter especially with cumulative dosages approaching 500 g. Patients exposed to greater than 1500 g of PPS are at significant risk of retinal toxicity.

Colon Myoelectric Activity Measured After Open Abdominal Surgery with a Noninvasive Wireless Patch System Predicts Time to First Flatus.

BACKGROUND: Passage of flatus after abdominal surgery signals resolution of physiological postoperative ileus (POI) and often, particularly after complex open surgeries, serves as the trigger to initiate oral feeding. To date, there is no objective tool that can predict time to flatus allowing for timely feeding and optimizing recovery. In an open, prospective study, we examine the use of a noninvasive wireless patch system that measures electrical activity from gastrointestinal smooth muscles in predicting time to first flatus. METHODS: Eighteen patients who underwent open abdominal surgery at El Camino Hospital, Mountain View, CA, were consented and studied. Immediately following surgery, wireless patches were placed on the patients' anterior abdomen. Colonic frequency peaks in the spectra were identified in select time intervals and the area under the curve of each peak times its duration was summed to calculate cumulative myoelectrical activity. RESULTS: Patients with early flatus had stronger early colonic activity than patients with late flatus. At 36 h post-surgery, a linear fit of time to flatus vs cumulative colonic myoelectrical activity predicted first flatus as much as 5 days (± 22 h) before occurrence. CONCLUSIONS: In this open, prospective pilot study, noninvasive measurement of colon activity after open abdominal surgery was feasible and predictive of time to first flatus. Interventions such as feeding can potentially be optimized based on this prediction, potentially improving outcomes, decreasing length of stay, and lowering costs.

Multimodal imaging of diabetic retinopathy.

PURPOSE OF REVIEW: Diabetic retinopathy is the most common microvascular complication of diabetes mellitus and a leading cause of blindness throughout the world. Ocular imaging continues to play a vital role in the diagnosis, management and monitoring of diabetic retinopathy. Major technological advancements in imaging over the past decade have improved our understanding and knowledge of diabetic retinopathy and therefore a multimodal approach to imaging has become the standard of care. RECENT FINDINGS: Updates to traditional technologies such as digital fundus photography along with recent advancements in optical coherence tomography (OCT) and OCT angiography (OCTA) have provided clinicians with new information and improved efficiency. SUMMARY: In this review, we describe the benefits and clinical applications of several imaging techniques in diabetic retinopathy including color photography, fluorescein angiography, OCT, OCTA and adaptive optics. Understanding the indications and limitations of each technology allows clinicians to gain the most information from each modality and thereby optimize patient care.

Simultaneous Subconjunctival Triamcinolone and Bevacizumab Injections for Management of Blepharokeratoconjunctivitis in Children.

PURPOSE: To report the efficacy of subconjunctival triamcinolone (Kenalog A-40, Alcon) and bevacizumab (Avastin, Genentech) injections in fraternal twins with blepharokeratoconjunctivitis (BKC) causing progressive, bilateral corneal neovascularization and scarring. METHODS: In this retrospective observational case series, two three-year-old male twins with BKC had presented with bilateral red eyes, photophobia, and frequent blinking. Examination of each child showed bilateral deep stromal and superficial corneal neovascularization, corneal infiltrates, multiple follicles on the palpebral conjunctiva bilaterally with blepharitis, and thick turbid sebum expressed from the Meibomian glands. Their disease progressed despite conventional treatment. Both twins were managed with subconjunctival triamcinolone injection and subconjunctival bevacizumab injection of each eye. RESULTS: The treatment resulted in improvement of symptoms, and examination over an 8-10-month period postinjections showed fading stromal corneal infiltrates, partially regressed corneal neovascularization, and reduced conjunctival injection without complications. CONCLUSION: This case series highlights the potential vision threatening complications of BKC. In addition to conventional management options, this report is the first published use of subconjunctival triamcinolone and bevacizumab injections for BKC in children in an attempt to minimize and improve corneal neovascularization and scarring and subsequently to retain useful vision.

The apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state.

Through their biased localization and function within the cell, polarity complex proteins are necessary to establish the cellular asymmetry required for tissue organization. Well-characterized germinal zones, mitogenic signals and cell types make the cerebellum an excellent model for addressing the crucial function of polarity complex proteins in the generation and organization of neural tissues. Deletion of the apical polarity complex protein Pals1 in the developing cerebellum results in a remarkably undersized cerebellum with disrupted layers in poorly formed folia and strikingly reduced granule cell production. We demonstrate that Pals1 is not only essential for cerebellum organogenesis, but also for preventing premature differentiation and thus maintaining progenitor pools in cerebellar germinal zones, including cerebellar granule neuron precursors in the external granule layer. In the Pals1 mouse mutants, the expression of genes that regulate the cell cycle was diminished, correlating with the loss of the proliferating cell population of germinal zones. Furthermore, enhanced Shh signaling through activated Smo cannot overcome impaired cerebellar cell generation, arguing for an epistatic role of Pals1 in proliferation capacity. Our study identifies Pals1 as a novel intrinsic factor that regulates the generation of cerebellar cells and Pals1 deficiency as a potential inhibitor of overactive mitogenic signaling.

Penetrating eye injury from a crayfish antenna.

This is the first reported case of eye injury caused by a crayfish antenna. A 20-year-old male crayfish diver sustained a scleral penetrating injury that led to a subconjunctival abscess. The foreign body was histologically similar to a crayfish antenna.

Clinicopathological report: bilateral choroidal metastases from papillary thyroid cancer.

Bilateral uveal metastases from papillary thyroid carcinoma are extremely rare. A 36-year-old woman with a 12-month history of papillary thyroid carcinoma presented with sudden loss of visual acuity and fields in the left eye. An examination and B-scan revealed a large, solid choroidal lesion in the left eye causing exudative retinal detachment. A small solid mass was also observed in the right eye fundus. Following left eye enucleation, immunohistopathology confirmed metastatic papillary thyroid carcinoma. The authors report the third known case of bilateral choroidal metastases.

Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy.

Adoptive cell therapy (ACT) with tumor-reactive lymphocytes in patients with refractory melanoma can result in tumor regression and prolonged survival. Generating tumor-reactive lymphocyte cultures is technically difficult and resource intensive; these limitations have restricted the widespread application of ACT. Tumor-infiltrating lymphocytes (TIL) from melanoma contain tumor antigen-reactive cells. The "standard" method for producing TIL cultures for clinical administration requires extended in vitro expansion in interleukin-2, then identification of tumor-reactive cells by immunologic assays. We show here that limitations in reagents and methods during screening underrepresent the actual reactivity of TIL cultures. Furthermore, the extended culture times necessitated by the screening assays resulted in telomere shortening and reduced expression of CD27 and CD28 in the TIL cultures, properties that our prior studies showed are correlated with in vivo persistence and clinical response. We have thus developed an alternative "young" TIL method that demonstrated superior in vitro attributes compared with standard TIL. This approach uses the entire resected tumor to rapidly expand TIL for administration without in vitro testing for tumor recognition. Our observations suggest that younger TIL can have an undetermined but high level of antigen reactivity, and other advantageous attributes such as long telomeres and high levels of CD27 and CD28. We suggest that minimally cultured, unselected lymphocytes represent an alternative strategy for generating TIL cultures suitable for use in ACT that, if effective in vivo, may facilitate the widespread application of this approach to a broader population of patients with melanoma.

Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4.

PURPOSE: Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) is an inhibitory receptor on T cells. Knocking out CTLA4 in mice causes lethal lymphoproliferation, and polymorphisms in human CTLA4 are associated with autoimmune disease. Trials of the anti-CTLA4 antibody ipilimumab (MDX-010) have resulted in durable cancer regression and immune-mediated toxicities. A report on the diagnosis, pathology, treatment, clinical outcome, and significance of the immune-mediated enterocolitis seen with ipilimumab is presented. PATIENTS AND METHODS: We treated 198 patients with metastatic melanoma (MM) or renal cell carcinoma (RCC) with ipilimumab. RESULTS: The overall objective tumor response rate was 14%. We observed several immune mediated toxicities including dermatitis, enterocolitis, hypophysitis, uveitis, hepatitis, and nephritis. Enterocolitis, defined by grade 3/4 clinical presentation and/or biopsy documentation, was the most common major toxicity (21% of patients). It presented with diarrhea, and biopsies showed both neutrophilic and lymphocytic inflammation. Most patients who developed enterocolitis responded to high-dose systemic corticosteroids. There was no evidence that steroid administration affected tumor responses. Five patients developed perforation or required colectomy. Four other patients with steroid-refractory enterocolitis appeared to respond promptly to tumor necrosis factor alpha blockade with infliximab. Objective tumor response rates in patients with enterocolitis were 36% for MM and 35% for RCC, compared with 11% and 2% in patients without enterocolitis, respectively (P = .0065 for MM and P = .0016 for RCC). CONCLUSION: CTLA4 seems to be a significant component of tolerance to tumor and in protection against immune mediated enterocolitis and these phenomena are significantly associated in cancer patients.

Nonalcoholic Fatty gallbladder disease: the influence of diet in lean and obese mice.

The obesity epidemic has contributed to an increased prevalence of gallstones and a higher percentage of chronic acalculous cholecystitis. Obesity is associated with Type II diabetes and hyperlipidemia in murine models. In addition, we have previously demonstrated that serum glucose, insulin, cholesterol, and triglycerides correlated with gallbladder contractility in murine models. However, the relative role of insulin resistance and gallbladder fat infiltration in this phenomenon remain unclear. Therefore, we tested the hypothesis that gallbladder wall lipids are related to obesity and diet and are inversely correlated with gallbladder contractility. One hundred lean control (C7BL/6J) and 36 obese leptin-deficient (Lep(ob)) 8-week-old female mice were fed either a chow diet or a 1.0% cholesterol, 15% butterfat (high-lipid) diet for four weeks. Pooled gallbladders were then analyzed for free fatty acids (FFA), phospholipids (PL), total cholesterol (TC), and triglycerides (TG). Cholesterol/phospholipid ratios were then calculated. The Lep(ob) mice fed a chow diet had significantly higher (P < 0.01) gallbladder lipids than the three other groups. The lean mice that were fed a high-lipid diet had increased (P < 0.05) gallbladder TC compared to the lean mice on a chow diet. In addition, the cholesterol/phospholipid ratio was significantly increased (P < 0.01) in the lean mice fed a high-lipid diet compared to the other three groups. Finally, the high-lipid diet decreased gallbladder FFA (P < 0.01), PL (P = 0.08), and TC (P < 0.05) in Lep(ob) mice. These data suggest that (1) obese mice have increased gallbladder lipids; (2) a high-cholesterol, high-fat diet increases gallbladder lipids and the cholesterol/phospholipid ratio in lean mice; but (3) decreases gallbladder fatty acids, phospholipids, and cholesterol in obese mice. Prior studies have documented similarly decreased gallbladder response to neurotransmitters in obese mice on a chow diet, as well as lean and obese mice on a high-lipid diet. Therefore, we conclude that leptin-deficient obesity and/or a high-fat diet causes nonalcoholic fatty gallbladder disease, which is manifested by diminished gallbladder contractility.