Management of metabolic syndrome and reduction in body weight in type II diabetic mice by inhibiting glycosphingolipid synthesis.

Metabolic syndrome is defined by hyperlipidemia and cardiovascular complications. We have examined whether inhibition of glycosphingolipid synthesis can interfere with metabolic syndrome in a male mouse model of type II diabetes (db/db). The db/db and control mice (C57/BL6) (n = 6) fed chow for 30 weeks received vehicle (5% Tween-80 in PBS; 100 µl), or a biopolymer-encapsulated D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (BPD) glycosphingolipid synthesis inhibitor daily via oral gavage for 6 weeks. Echocardiography revealed increased Ao-IMT in db/db mice compared to control. However, BPD decreased Ao-IMT, monohexosylceramide and dihexosylceramide, LDL, triglycerides, glucose, and raised HDL levels in db/db mice. This was due to increased gene expression of HMG-CoA reductase, LDLr, SREBP2, and bile acids: Cy7-a hydroxylase, LXR and FXR, lipoprotein lipase, VLDL receptor and PPAR. Treatment also increased the expression of superoxide dismutase-II to reduce the pro-oxidant status in these mice. We observed that decreased cholesterol levels correlated with decreased cholesterol sensing proteins e.g. NPC1 gene/protein expression and mammalian target of rapamycin (mTORC-1) and reduced body weight. Thus, glycosphingolipid synthesis inhibition is a novel approach to manage metabolic syndrome and reduce body weight in diabetic mice and with potential applications in humans.

Making common duct exploration common-balloon sphincteroplasty as an adjunct to transcystic laparoscopic common bile duct exploration for pediatric patients.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) at the time of cholecystectomy has well-established benefits for managing pediatric choledocholithiasis. However, providers increasingly favor ERCP pre-or-post laparoscopic cholecystectomy (ERCP+LC) due to perceived complexity of LCBDE. We refined a stepwise method employing wire-ready balloon dilation of the Sphincter of Oddi. This study compares outcomes of balloon sphincteroplasty (LCBDE+BSP) with standard transcystic LCBDE (LCBDE-STD) and ERCP+LC. METHODS: We performed a retrospective chart review of pediatric patients who underwent LCBDE-STD and LCBDE+BSP since 2018. A report of consecutive choledocholithiasis patients prior to 2018 yielded an ERCP+LC cohort. Age, operative time, complications, and length of stay (LOS) were compared across all groups. Success rate and fluoroscopy time were compared between LCBDE groups. RESULTS: 44 patients were identified (14:LCBDE-STD; 15:LCBDE+BSP; 15:ERCP+LC) . There was no difference in patient age or BMI. Operative time was longer in the LCBDE+BSP group (p =< 0.05). ERCP+LC demonstrated increased LOS (4.36 ± 2.78 vs 1.31 ± 0.93; p =< 0.05) and complications compared to LCBDE groups including three stent placements and one stent migration. LCBDE+BSP had a higher success rate than LCBDE-STD (100% vs 78%; p = 0.06). The three patients who failed LCBDE-STD required postoperative ERCP. Average fluoroscopy time was not significantly impacted by addition of sphincteroplasty. CONCLUSION: Incorporating LCBDE into standard management of pediatric choledocholithiasis reduces LOS and avoids additional invasive procedures regardless of the specific technique employed. This stepwise approach to wire-ready cholangiography with balloon sphincteroplasty is a viable method for LCBDE that utilizes techniques familiar to pediatric surgeons and provides definitive management under a single anesthetic. LEVEL OF EVIDENCE: Level III.

Pickles and warfarin interaction: a case-based review.

A 36-year-old woman with a history of lupus and antiphospholipid syndrome controlled by warfarin presented to the hospital with left periorbital ecchymosis. She was found to have an INR of 9 despite maintaining her normal warfarin dose of 12.5 mg/15 mg alternating qd. The only identifiable precipitating factor was that the patient recently stopped eating dill pickles. Limiting dietary vitamin K while on warfarin therapy was once considered best practice. However, studies have demonstrated that maintaining a consistent intake of vitamin K is more important than the quantity. Still, many patients on warfarin remain unaware of which foods contain large amounts of vitamin K and are, therefore, susceptible to bleeding sequelae. Practitioners should be educated to inform patients to consume a steady amount of vitamin K in their diet, identify which foods contain vitamin K, and include pickles on that list.