Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT). The former activity is furnished by the CCD, but the Angptl4 domain responsible for stimulating adipocyte lipolysis is unknown. We show here that the purified FLD of Angptl4 is sufficient to stimulate lipolysis in mouse primary adipocytes and that increasing circulating FLD levels in mice through adenovirus-mediated overexpression (Ad-FLD) not only induces WAT lipolysis but also reduces diet-induced obesity without affecting LPL activity. Intriguingly, reduced adiposity in Ad-FLD mice was associated with increased oxygen consumption, fat utilization, and the expression of thermogenic genes ( and ) in subcutaneous WAT. Moreover, Ad-FLD mice exhibited increased glucose tolerance. Chronically enhancing WAT lipolysis could produce ectopic steatosis because of an overflow of lipids from the WAT to peripheral tissues; however, this did not occur when Ad-FLD mice were fed a high-fat diet. Rather, these mice had reductions in both circulating triacylglycerol levels and the mRNA levels of lipogenic genes in the liver and skeletal muscle. We conclude that separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals lipolytic and thermogenic properties with therapeutic relevance to obesity and diabetes.

Context The increased incidence of thyroid cancer globally over the past several decades is principally attributed to small, indolent papillary thyroid cancers. A possible concomitant increase in thyroid cancer-specific mortality remains debated. Objective The changes in thyroid cancer incidence and incidence-based mortality were assessed using a large population-based cohort over an 18-year period. Design & Patients A retrospective analysis of all thyroid cancers reported in the California Cancer Registry was performed (2000–2017). Age-adjusted incidence and incidence-based mortality rates were analyzed using a log-linear model to estimate annual percent change. Results We identified 69 684 individuals (76% female, median age 50 years) diagnosed with thyroid cancer. The incidence of thyroid cancer increased across all histological subtypes (papillary, follicular, medullary, and anaplastic) and all tumor sizes. The incidence increased from 6.43 to 11.13 per 100 000 person-years (average increase 4% per year; P < 0.001) over the study period. Thyroid cancer-specific mortality rates increased on average by 1.7% per year (P < 0.001). The increased mortality rates were greater in men (2.7% per year, P < 0.001) and patients with larger tumors (2-4 cm) (3.4% per year, P < 0.05). Conclusions Data from this statewide registry demonstrate that the incidence of thyroid cancer is increasing, and that this phenomenon is not restricted to small papillary thyroid cancers. Rising incidence in thyroid cancers of all sizes with concurrent increase of incidence-based mortality in men and those with larger tumors suggest a true increase in clinically significant disease.

Postoperative biliary complications have been reported to occur in 10% to 33% of pediatric liver transplantation (LT) recipients. Percutaneous intervention has become the primary treatment method for these complications; however, the efficacy and outcomes of these patients have not been well studied. Institutional pediatric LT from 1998 to 2019 were retrospectively reviewed to determine the patients referred for percutaneous treatment of post‐LT biliary strictures. Clinical parameters, percutaneous transhepatic cholangiograms (PTCs), biliary catheter placement, cholangioplasty, and long‐term outcomes were analyzed. Of the 396 consecutive pediatric LT recipients during our study period, 50 (12.6%) were diagnosed with biliary strictures on PTC. LT biliary reconstructions were Roux‐en‐Y hepaticojejunostomy in 28 patients (56%), choledochojejunostomy in 11 patients (22%), and choledochocholedochostomy in 11 patients (22%). Median age at LT was 23.2 months (interquartile range [IQR], 10.9‐90.6), and 14 patients (28%) developed hepatic artery thrombosis. A total of 44 patients (88%) were treated with internal/external biliary catheters, of whom 38 (76%) underwent balloon cholangioplasty. By 12 months, 84% of patients had complete stricture resolution and catheter removal. Median total duration of catheter drainage was 152 days (IQR, 76‐308). A total of 8 patients required additional surgery (biliary reconstruction or repeat LT [re‐LT]) or died with a drainage catheter in place from complications unrelated to PTC intervention. Among the 6 patients (12%) treated with unilateral external biliary drainage catheters, 2 had catheters removed for inadequate drainage but then had spontaneous biliary obstruction resolution, 1 underwent duct reconstruction, and 3 required long‐term catheterization. Biliary strictures following pediatric LT can be successfully treated with internal/external biliary drainage catheters and cholangioplasty if the stricture can be crossed. However, patients with isolated strictured ducts may require long‐term external catheter drainage until re‐LT or percutaneous obliteration of isolated ducts.

Normocalcaemic primary hyperparathyroidism is a condition that can present with intermittent hypercalcemia or may evolve into hypercalcemic primary hyperparathyroidism. This milder biochemical entity remains incompletely understood because of a lack of long-term health outcomes regarding both medical and surgical approaches to its management. Medical therapies have shown some efficacy. A limited number of studies have found that bisphosphonates increase bone mineral density, and cal

OBJECTIVE The objective of this study was to determine factors associated with admission to the hospital through the emergency room (ER) for patients with a primary diagnosis of low-back pain (LBP). The authors further evaluated the impact of ER admission and patient characteristics on mortality, discharge disposition, and hospital length of stay. METHODS The authors conducted a retrospective analysis of patients with LBP discharged from hospitals according to the Nationwide Inpatient Sample (NIS) between 1998 and 2007. Univariate comparisons of patient characteristics according to the type of admission (ER versus non-ER) were conducted. Multivariate analysis evaluated factors associated with an ER admission, risk of mortality, and nonroutine discharge. RESULTS According to the NIS, approximately 183,151 patients with a primary diagnosis of LBP were discharged from US hospitals between 1998 and 2007. During this period, an average of 65% of these patients were admitted through the ER, with a significant increase from 1998 (54%) to 2005 (71%). Multivariate analysis revealed that uninsured patients (OR 2.1, 95% CI 1.7–2.6, p < 0.0001) and African American patients (OR 1.5, 95% CI 1.2–1.7, p < 0.0001) were significantly more likely to be admitted through the ER than private insurance patients or Caucasian patients, respectively. Additionally, a moderate but statistically significant increase in the likelihood of ER admission was noted for patients with more preexisting comorbidities (OR 1.1, 95% CI 1.0–1.2, p < 0.001). An 11% incremental increase in the odds of admission through the ER was observed with each year increment (OR 1.1, 95% CI 1.0–1.2, p < 0.001). Highest income patients ($45,000+) were more likely to be admitted through the ER (OR 1.3, 95% CI 1.1–1.6, p = 0.007) than the lowest income cohort. While ER admission did not impact the risk of mortality (OR 0.95, 95% CI 0.60–1.51, p = 0.84), it increased the odds of a nonroutine discharge (OR 1.39, 95% CI 1.26–1.53, p < 0.0001). CONCLUSIONS A significant majority of patients discharged from hospitals in the US from 1998 to 2007 with a primary diagnosis of LBP were admitted through the ER, with more patients being admitted via this route each year. These patients were less likely to be discharged directly home compared with patients with LBP who were not admitted through the ER. Uninsured and African American patients with LBP were more likely to be admitted through the ER than their counterparts, as were patients with more preexisting health problems. Interestingly, patients with LBP at the highest income levels were more likely to be admitted through hospital ERs. The findings suggest that socioeconomic factors may play a role in the utilization of ER resources by patients with LBP, which in turn appears to impact at least the short-term outcome of these patients.