The Journey and Barriers to Treatment of Patients With Renal Nutcracker Syndrome.

OBJECTIVE: To better understand renal nutcracker syndrome (NCS) from a patients' perspective starting at presentation and followed through to diagnosis and management METHODS: This descriptive study was conducted on a national level via a self-selected online survey distributed via river sampling by a post on the Facebook Page 'Renal Nutcracker Syndrome Support Group.' RESULTS: Of the 22 responses collected, 95.5% were female and 91% self-identified as White. 43% experienced symptoms as teenagers and 62% were diagnosed as young adults. Prior to receiving a definitive diagnosis, over half of the respondents were worked up for kidney stones (57%) and ovarian cysts (48%) and saw at least 10-15 providers. Nearly 80% experienced constant pain throughout the day. Pain management included prescription oral pain relievers (38%), prescription patches (29%), and physical therapy (19%). Surgical procedures included nephrectomy with auto transplant (38%), left renal vein transposition (10%), and laparoscopic extravascular stent placement (10%). Respondents had high healthcare utilization for management of NCS. Nearly 30% were unable to work and had filed for disability. CONCLUSION: Awareness of NCS should increase among healthcare providers of all specialties to improve quality of care to those living with NCS. It is crucial to keep NCS within the differential diagnosis in patients presenting with gross hematuria and unusual abdominal and/or flank pain.

Correction to: Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Partitioning of adipose lipid metabolism by altered expression and function of PPAR isoforms after bariatric surgery.

BACKGROUND: Bariatric surgery remains the most effective treatment for reducing adiposity and eliminating type 2 diabetes; however, the mechanism(s) responsible have remained elusive. Peroxisome proliferator-activated receptors (PPAR) encompass a family of nuclear hormone receptors that upon activation exert control of lipid metabolism, glucose regulation and inflammation. Their role in adipose tissue following bariatric surgery remains undefined. MATERIALS AND METHODS: Subcutaneous adipose tissue biopsies and serum were obtained and evaluated from time of surgery and on postoperative day 7 in patients randomized to Roux-en-Y gastric bypass (n=13) or matched caloric restriction (n=14), as well as patients undergoing vertical sleeve gastrectomy (n=33). Fat samples were evaluated for changes in gene expression, protein levels, ß-oxidation, lipolysis and cysteine oxidation. RESULTS: Within 7 days, bariatric surgery acutely drives a change in the activity and expression of PPARγ and PPARδ in subcutaneous adipose tissue thereby attenuating lipid storage, increasing lipolysis and potentiating lipid oxidation. This unique metabolic alteration leads to changes in downstream PPARγ/δ targets including decreased expression of fatty acid binding protein (FABP) 4 and stearoyl-CoA desaturase-1 (SCD1) with increased expression of carnitine palmitoyl transferase 1 (CPT1) and uncoupling protein 2 (UCP2). Increased expression of UCP2 not only facilitated fatty acid oxidation (increased 15-fold following surgery) but also regulated the subcutaneous adipose tissue redoxome by attenuating protein cysteine oxidation and reducing oxidative stress. The expression of UCP1, a mitochondrial protein responsible for the regulation of fatty acid oxidation and thermogenesis in beige and brown fat, was unaltered following surgery. CONCLUSIONS: These results suggest that bariatric surgery initiates a novel metabolic shift in subcutaneous adipose tissue to oxidize fatty acids independently from the beiging process through regulation of PPAR isoforms. Further studies are required to understand the contribution of this shift in expression of PPAR isoforms to weight loss following bariatric surgery.

Laparoscopic conversion of vertical banded gastroplasty to a Roux-en-Y gastric bypass.

The vertical banded gastroplasty was the mainstay of bariatric surgery for over a decade. Though this procedure is now rarely performed many of these patients will present with failure or maladaptive eating and its sequelae. Some of these patients who demonstrate the motivation for lifestyle modification as well as many of these with complications will be candidates for revisional surgery. This article reviews the technical challenges in performing these revisions using minimally invasive techniques. In addition it reviews outcomes of laparoscopic conversion and tips for patient selection and success.

Accelerated internalization and detoxification of endotoxin by anti-lipopolysaccharide antibody is an Fc receptor--mediated process.

BACKGROUND: Interaction between lipopolysaccharide (LPS), LPS-binding protein, and the CD14 receptor at the surface of LPS-responsive cells results in inflammatory cytokine release and internalization and detoxification of LPS. Monoclonal antibodies (mAbs) raised against the deep-core lipid A or the O-linked polysaccharide moieties of LPS accelerate internalization and detoxification of LPS without stimulating cytokine release. This study was conducted to test the hypothesis that the antibody-mediated internalization of LPS is an Fc receptor (FcR)--mediated process. METHODS: Fluoroisothiocyanate (FITC)-conjugated Escherichia coli O111:B4 LPS was incubated with RAW 264.7 cells and allowed to internalize for 2 hours in the presence and absence of anti-LPS, anti-CD14, and isotype control mAbs, and Fab fragments from the anti-CD14, anti--Fc receptor, and control mAbs. Tumor necrosis factor--alpha (TNF-alpha) release was measured by WEHI 164 cell bioassay. FITC-LPS uptake was measured by flow cytometry. Statistical analysis was by analysis of variance and Fisher exact test. RESULTS: Addition of anti-LPS antibodies resulted in a 30- to 40-fold acceleration of LPS internalization (P <.01) in agreement with previous studies. This increase was blunted by anti-CD14 and also by isotype control holo-antibody (P <.01), but not by Fab fragments from anti-CD14 or isotype control antibody. Both anti-FcR antibodies and Fab fragments blocked anti-LPS antibody--stimulated uptake of FITC-LPS. Both intact anti-CD14 holo-antibody and Fab fragments blocked TNF-alpha release (P <.01). CONCLUSIONS: Clearance and detoxification of LPS are thought to be essential to the host response to endotoxin. It has been shown that antibodies to LPS accelerate its internalization by monocytic cell lines without increasing the elaboration of cytokines. We found that specific blockade of CD14 by Fab fragments could block TNF-alpha release but not alter the accelerated internalization of LPS produced by anti-LPS antibodies. In contrast, a nonspecific blockade of internalization was produced by competing antibody, which suggests a mechanistic role for the FcR. Specific blockade of FcR by either holo-antibody or Fab fragments blocked accelerated internalization, which confirms a FcR mechanism. We conclude that the accelerated internalization of LPS produced by anti-LPS antibody is an Fc receptor--mediated process. These results have significance for the development of adjuvant immunotherapy for gram-negative bacterial sepsis.