The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on revisional bariatrics.

BACKGROUND: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program designated bariatric surgery as a clinical pathway. Among the tiers of the Masters Program, revisional bariatric surgery is the highest tier of "mastery" within the pathway. This article presents the top 10 seminal studies representing the current landscape of revisional bariatrics. METHODS: The literature was systematically searched and seminal articles designated by consensus agreement of the SAGES Metabolic and Bariatric Surgery committee using multiple criteria, including impact on the field, citation frequency, and expert opinion. Articles were reviewed by committee members and presented in summarized fashion. RESULTS: The top 10 papers are presented in grouped thematic categories covering the early evolution of revisional bariatrics, changing criteria for reoperative bariatric surgery, divergence of revision versus conversion bariatric surgery, and recent technologic innovations in revisional bariatric surgery. Each summary is presented with expert appraisal and commentary. CONCLUSION: These seminal papers represent a snapshot of the dynamic field of revisional bariatric surgery and emphasize the need to not only remain current with contemporary trends but also keep a patient-oriented perspective on patient and intervention selection for optimal success.

Neuromuscular treatment approach for women with chronic pelvic pain syndrome improving pelvic pain and functionality.

AIMS: Reporting the effects of treating underlying myofascial dysfunction and neuropathic pain in women with chronic pelvic pain syndrome (CPPS). METHODS: Retrospective longitudinal study of 186 women with CPPS treated with ultrasound-guided peripheral nerve blocks and trigger point injections to pelvic floor muscles alongside pelvic floor physical therapy once weekly for 6 weeks in an outpatient setting. Visual Analogue Scale (VAS) and Functional Pelvic Pain Scale (FPPS) questionnaires quantified pain and function in the pelvis. Working, intercourse, sleeping, walking, running, lifting, bladder, and bowel were the function categories. Statistical significance was established by p value less than .05 in paired two-sample t-test. RESULTS: VAS improved by 2.14 where average VAS before treatment was 6.61 (standard deviation [SD] 2.45; p < .05, 95% confidence interval [CI] = 6.26-6.96) and average VAS after treatment was 4.47 (SD 2.71; p < .05, 95% CI = 4.08-4.86). Total FPPS decreased by 3.38 from 11.26 (SD 6.51; p < .05, 95% CI = 10.32-12.19) before treatment to 7.88 (SD 6.22; p < .05, 95% CI = 6.99-8.78) after treatment. Working, intercourse, and sleeping accounted for the highest statistically significant improvement. CONCLUSION: Findings support the success of the comprehensive treatment protocol. Patients who had persistent symptoms after a full course of pelvic floor physical therapy experienced improvements in pain levels and function once it was combined with ultrasound-guided nerve blocks and trigger point injections, interactively treating underlying neuromuscular dysfunction.

'There isn't a checklist in the world that's got that on it': Special needs teachers' opinions on the assessment and teaching priorities of pupils on the autism spectrum.

Two focus groups were conducted with special needs teachers to: (a) identify barriers to learning for autistic pupils, (b) consider broad assessment domains and specific skills or behaviours which teachers consider important for these pupils, and (c) give their opinions on teacher assessments. Data analysis resulted in six main themes: (a) barriers to learning, (b) teacher priorities for autistic pupils, (c) ways of overcoming barriers, (d) the concept of 'true mastery', (e) assessing the bigger picture, and (f) practicalities of assessment. Results showed that teachers have priorities for the pupils they know well and concerns about the assessments they regularly use. To ensure face and content validity of teacher assessments, and for assessments to be useful to and valued by the teachers who use them, it is recommended that teachers have opportunities to input during various aspects of the assessment development process.

Robot-assisted versus laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a propensity score-matched comparative analysis using the 2015-2016 MBSAQIP database.

BACKGROUND: Robotic-assisted bariatric surgery is part of the armamentarium in many bariatric centers. However, limited data correlate the robotic benefits to with clinical outcomes. This study compares 30-day outcomes between robotic-assisted and laparoscopic procedures for Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). METHODS: Using the 2015-2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database, patients between18- and 65-year-old were included. To adjust for potential confounders, 1:1 propensity-score matching (PSM) was performed using 22 preoperative characteristics. Second PSM analysis was performed adding operative time and conversion rate. RESULTS: 269,923 patients underwent SG (n = 190,494) or RYGB (n = 79,429). The operative time was significantly longer in the Robotic-assisted compared to laparoscopic approach either for SG (102.58 ± 46 vs. 73.38 ± 36; P < 0.001) or for RYGB (158.29 ± 65 vs. 120.17 ± 56; P < 0.001). In the SG cohort (12,877 matched cases), the robotic approach showed significant reduction of postoperative bleeding (0.16% vs. 0.43%; P < 0.001) and strictures (0.19% vs. 0.33%; P = 0.04) with similar results in the other 30-day outcomes in both analyses. Similarly, for the RYGB cohort (5780 matched cases), the robotic approach showed significantly fewer requirements for blood transfusions (0.64% vs. 1.16%; P = 0.004) with no statistically different results for the other's outcomes. Conversely, when adding operative time and conversion rate to the PSM analysis, the robotic platform showed significantly shorter length of stay (2.12 ± 1.9 vs. 2.30 ± 3.1 days; P < 0.001), reduction of anastomotic leak (0.52% vs. 0.92%; P = 0.01), renal complications (0.16% vs. 0.38%; P = 0.004), and venous thromboembolism (0.24% vs. 0.52%; P = 0.02). CONCLUSIONS: Our findings show that postoperative bleeding and blood transfusion are significantly reduced with the robotic platform, and after correcting for all factors including operative time, the robotic-assisted approach is associated with better postoperative outcomes especially for RYGB.

Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin.

Sapje-like (sap(cl100)) was one of eight potential zebrafish muscle mutants isolated as part of an early-pressure screen of 500 families. This mutant shows a muscle tearing phenotype similar to sapje (dys-/-) and both mutants fail to genetically complement suggesting they have a mutation in the same gene. Protein analysis confirms a lack of dystrophin in developing sapje-like embryos. Sequence analysis of the sapje-like dystrophin mRNA shows that exon 62 is missing in the dystrophin transcript causing exon 63 to be translated out of frame terminating translation at a premature stop codon at the end of exon 63. Sequence analysis of sapje-like genomic DNA identified a mutation in the donor splice junction at the end of dystrophin exon 62. This mutation is similar to splicing mutations associated with human forms of Duchenne Muscular Dystrophy. Sapje-like is the first zebrafish dystrophin splicing mutant identified to date and represents a novel disease model which can be used in future studies to identify therapeutic compounds for treating diseases caused by splicing defects.

Isolation and transcriptome analysis of adult zebrafish cells enriched for skeletal muscle progenitors.

INTRODUCTION: Over the past 10 years, the use of zebrafish for scientific research in the area of muscle development has increased dramatically. Although several protocols exist for the isolation of adult myoblast progenitors from larger fish, no standardized protocol exists for the isolation of myogenic progenitors from adult zebrafish muscle. METHODS: Using a variant of a mammalian myoblast isolation protocol, zebrafish muscle progenitors have been isolated from the total dorsal myotome. These zebrafish myoblast progenitors can be cultured for several passages and then differentiated into multinucleated, mature myotubes. RESULTS: Transcriptome analysis of these cells during myogenic differentiation revealed a strong downregulation of pluripotency genes, while, conversely, showing an upregulation of myogenic signaling and structural genes. CONCLUSIONS: Together these studies provide a simple, yet detailed method for the isolation and culture of myogenic progenitors from adult zebrafish, while further promoting their therapeutic potential for the study of muscle disease and drug screening.

The preliminary validity and reliability of the Assessment of Barriers to Learning in Education - Autism.

BACKGROUND: Few robust autism-specific outcome assessments have been developed specifically for use by teachers in special schools. The Assessment of Barriers to Learning in Education - Autism (ABLE-Autism) is a newly developed teacher assessment to identify and show progress in barriers to learning for pupils on the autism spectrum with coexisting intellectual disabilities. AIMS: This study aimed to conduct a preliminary validity and reliability evaluation of the ABLE-Autism. METHODS AND PROCEDURES: Forty-eight autistic pupils attending special schools were assessed using the ABLE-Autism. Multi-level modelling was used to evaluate test-retest reliability, internal consistency and convergent validity with the Teacher Autism Progress Scale. OUTCOMES AND RESULTS: Results showed excellent test-retest reliability and internal consistency. A large effect size suggested that the ABLE-Autism is strongly correlated with the Teacher Autism Progress Scale. Teacher feedback was positive and suggested that the ABLE-Autism is easily understood by teachers, relevant to autistic pupils in special schools, and adequately covers the skills and behaviours that teachers believe are important to assess for these pupils. CONCLUSIONS AND IMPLICATIONS: Although further validation is recommended, the preliminary evaluation of the ABLE-Autism suggests that it is a useful and has the potential to be an effective outcome assessment for autistic pupils in special schools.

Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy.

Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen. By isolating the individual glyceollin isomers (I, II, and III), we have identified the active antiestrogenic component by using competition binding assays with human ERalpha and in an estrogen-responsive element-based luciferase reporter assay. We identified glyceollin I as the active component of the combined glyceollin mixture. Ligand-receptor modeling (docking) of glyceollin I, II, and III within the ERalpha ligand binding cavity demonstrates a unique type II antiestrogenic confirmation adopted by glyceollin I but not isomers II and III. We further compared the effects of glyceollin I to the antiestrogens, 4-hydroxytamoxifen and ICI 182,780 (fulvestrant), in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on 17beta-estradiol-stimulated expression of progesterone receptor and stromal derived factor-1alpha. Our results establish a novel inhibition of ER-mediated gene expression and cell proliferation/survival. Glyceollin I may represent an important component of a phytoalexin-enriched food (activated) diet in terms of chemoprevention as well as a novel therapeutic agent for hormone-dependent tumors.

Modeling human muscle disease in zebrafish.

Zebrafish reproduce in large quantities, grow rapidly, and are transparent early in development. For these reasons, zebrafish have been used extensively to model vertebrate development and disease. Like mammals, zebrafish express dystrophin and many of its associated proteins early in development and these proteins have been shown to be vital for zebrafish muscle stability. In dystrophin-null zebrafish, muscle degeneration becomes apparent as early as 3 days post-fertilization (dpf) making the zebrafish an excellent organism for large-scale screens to identify other genes involved in the disease process or drugs capable of correcting the disease phenotype. Being transparent, developing zebrafish are also an ideal experimental model for monitoring the fate of labeled transplanted cells. Although zebrafish dystrophy models are not meant to replace existing mammalian models of disease, experiments requiring large numbers of animals may be best performed in zebrafish. Results garnered from using this model could lead to a better understanding of the pathogenesis of the muscular dystrophies and the development of future therapies.

A Single-center Experience Examining the Length of Stay and Safety of Early Discharge After Laparoscopic Roux-en-Y Gastric Bypass Surgery.

PURPOSE: This study's objective was to describe our experience and evaluate the safety of early discharge (ED) following laparoscopic Roux-en-Y gastric bypass (LRYGB) in a specific patient population. MATERIALS AND METHODS: Patients undergoing LRYGB at Montefiore Medical Center were retrospectively reviewed. Patients readmitted in the first 30 days following surgery were compared to those patients who were not readmitted. Data analysis was used to compare groups and to determine factors associated with readmission. In addition to patient demographics, length of stay (LOS) was analyzed as an independent risk factor for readmission. RESULTS: A total of 630 LRYGB were performed during this period. There were 5.1% (n = 32) of patients that required readmission within 30 days of discharge. Readmitted patients had a higher BMI (50.0 vs. 45.8; p = 0.006) and there was a trend for them to be younger (38.4 years vs. 42.0; p = 0.07). There was an increased rate of ED in 2015 (36.7%, n = 121) compared to 2014 (29.9%, n = 90). The readmission rate for ED for the study period was 4.7% (n = 10). There were no observed mortalities in our early discharge group of patients. CONCLUSIONS: Discharge on post-operative day 1 following a LRYGB is safe and is not associated with an increased likelihood of being readmitted within 30 days of discharge. Our single-center experience helps to better characterize current patient profiles and length of stay trends within the field and can be used to establish a randomized controlled trial for discharging patients early after LRYGB.

p53 pathway gene single nucleotide polymorphisms and chronic lymphocytic leukemia.

The p53 pathway plays a critical role in chronic lymphocytic leukemia (CLL). The association between the single-nucleotide polymorphism (SNPs) within the p53 gene (R72P) and its downstream target/regulators, BAX (G125A) and MDM2 (SNP309), and clinical parameters/prognostic markers was investigated in 83 CLL patients. Although the p53 R72P SNPs and MDM2 SNP309 did not associate with any of the parameters studied, the BAX G125A SNPs was associated with a more advanced Binet stage at diagnosis, supporting a potential role for this variant in CLL disease progression. In reporter assays, however, the BAX 5' untranslated region G125A SNPs surprisingly caused a 1.8-fold increase in basal promoter activity and did not alter the ability of p53 to trans-activate the promoter. Further studies are required to understand the role of SNPs in the p53 pathway in CLL.

Herpesvirus pan encodes a functional homologue of BHRF1, the Epstein-Barr virus v-Bcl-2.

BACKGROUND: Epstein-Barr virus (EBV) latently infects about 90% of the human population and is associated with benign and malignant diseases of lymphoid and epithelial origin. BHRF1, an early lytic cycle antigen, is an apoptosis suppressing member of the Bcl-2 family. In vitro studies imply that BHRF1 is dispensable for both virus replication and transformation. However, the fact that BHRF1 is highly conserved not only in all EBV isolates studied to date but also in the analogous viruses Herpesvirus papio and Herpesvirus pan that infect baboons and chimpanzees respectively, suggests BHRF1 may play an important role in vivo. RESULTS: Herpesvirus papio BHRF1 has been shown to function in an analogous manner to EBV BHRF1 in response to DNA damaging agents in human keratinocytes. In this study we show that the heterologous expression of the previously uncharacterised Herpesvirus pan BHRF1 in the human Burkitt's lymphoma cell line Ramos-BL provides similar anti-apoptotic functions to that of EBV BHRF1 in response to apoptosis triggered by serum withdrawal, etoposide treatment and ultraviolet (UV) radiation. We also map the amino acid changes onto the recently solved structure of the EBV BHRF1 and reveal that these changes are unlikely to alter the 3D structure of the protein. CONCLUSIONS: These findings show that the functional conservation of BHRF1 extends to a lymphoid background, suggesting that the primate virus proteins interact with cellular proteins that are themselves highly conserved across the higher primates. Further weight is added to this suggestion when we show that the difference in amino acid sequences map to regions on the 3D structure of EBV BHRF1 that are unlikely to change the conformation of the protein.

A Retrospective Review of Patients Undergoing Lateral Canthoplasty Techniques to Manage Existing or Potential Lower Eyelid Malposition: Identification of Seven Key Preoperative Findings.

BACKGROUND: Lateral canthal procedures are often indicated to correct or prevent lower eyelid malposition. When determining an appropriate lateral canthal procedure, planning is essential and includes proper analysis and identification of any contributory anatomical factors. METHODS: A 12-month retrospective review was performed on patients undergoing lateral canthal procedures. Important components of the preoperative examination were studied to relate patient anatomy and results. Outcomes were followed for a minimum of 5 years. RESULTS: Of 288 consecutive lower eyelid canthal procedures, a total of 146 met the inclusion criteria. Common designated abnormal preoperative findings included a negative vector (62 percent), lid margin eversion (12 percent), scleral show (21 percent), neutral or negative canthal tilt (49 percent and 18 percent, respectively), and lateral canthus -to -orbital rim distance of more than 1 cm (11 percent). The distribution of lateral canthal procedures performed in our study population included inferior retinacular lateral canthopexy (n = 36), inferior retinacular lateral canthoplasty (n = 88), tarsal strip lateral canthoplasty (n = 15), and dermal-orbicular pennant lateral canthoplasty (n = 7). Successful outcomes were noted to be 86 percent and 91 percent according to surgeons and patients, respectively. CONCLUSIONS: Specific findings on the preoperative physical examination identify when simple or more complex lateral canthal procedures should be performed. The authors report seven key physical findings that should be documented to effectively determine a lateral canthal procedure that is appropriate for prevention and management of lower eyelid malposition. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Blinding measured: a systematic review of randomized controlled trials of acupuncture.

Background. There is no agreement among researchers on viable controls for acupuncture treatment, and the assessment of the effectiveness of blinding and its interpretation is rare. Purpose. To systematically assess the effectiveness of blinding (EOB) in reported acupuncture trials; to explore results of RCTs using a quantitative measure of EOB. Data Sources. A systematic review of published sham RCTs that assessed blinding. Study Selection. Five hundred and ninety studies were reviewed, and 54 studies (4783 subjects) were included. Data Extraction. The number of patients who guessed their treatment identity was extracted from each study. Variables with possible influence on blinding were identified. Data Synthesis. The blinding index was calculated for each study. Based on blinding indexes, studies were congregated into one of the nine blinding scenarios. Individual study characteristics were explored for potential association with EOB. Limitations. There is a possibility of publication or reporting bias. Conclusions. The most common scenario was that the subjects believed they received verum acupuncture regardless of the actual treatment received, and overall the subject blinding in the acupuncture studies was satisfactory, with 61% of study participants maintaining ideal blinding. Objectively calculated blinding data may offer meaningful and systematic ways to further interpret the findings of RCTs.

Is chemical incompatibility responsible for chondrocyte death induced by local anesthetics?

BACKGROUND: Chondrolysis associated with intra-articular administration of local anesthetics has been attributed to chondrocyte death induced by the local anesthetics. The mechanism of how the local anesthetics cause chondrocyte death is not clear. PURPOSE: This study was conducted to determine whether and how the local anesthetics cause chondrocyte death. STUDY DESIGN: Controlled laboratory study. METHODS: Bovine articular chondrocytes in suspension culture were treated for 1 hour with phosphate-buffered saline or phosphate-buffered saline/medium mixture (as controls); 1% lidocaine alone; 0.25% to 0.5% bupivacaine alone; phosphate-buffered saline with pH values of 4.5, 3.8, 3.4, and 2.4; or mixtures of the local anesthetics and cell culture medium or human synovial fluid. Chondrocyte viability was analyzed by flow cytometry using the LIVE/DEAD Viability/Cytotoxicity Kit. RESULTS: In 1% lidocaine-alone or 0.25% to 0.5% bupivacaine-alone groups, the rate of cell death was 11.8% to 13.3% of bovine articular chondrocytes, whereas the phosphate-buffered saline control had 8.4% of cell death. Increased chondrocyte death was only found when the pH value of phosphate-buffered saline dropped to < or = 3.4. In contrast, when bupivacaine was mixed with cell culture medium, needle-like crystals were formed, which was accompanied with 100% death of chondrocytes. Lidocaine did not form visible crystals when it was mixed with culture medium, but the mixtures caused death of over 96% of chondrocytes (P < .001). CONCLUSION: Less than 5% of chondrocyte death was attributable to the anesthetics when applied to the cells alone or in phosphate-buffered saline-diluted solution. Acidity (as low as pH 3.8) or epinephrine in the anesthetic solutions could not account for chondrocyte death. However, chemical incompatibility between the local anesthetics and cell culture medium or human synovial fluid may be the cause of chondrocyte death. CLINICAL RELEVANCE: Intra-articular administration of lidocaine and bupivacaine is not an indicated usage of either anesthetic, although such a usage has become a common practice. Physicians should be aware of the potential incompatibility of the drug and synovial fluid.

Identification of the potent phytoestrogen glycinol in elicited soybean (Glycine max).

The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists in vitro and in vivo. The discovery of the glyceollins' ability to inhibit cancer cell proliferation has led to the analysis of estrogenic activities of other induced isoflavones. In this study, we investigated a novel isoflavone, glycinol, a precursor to glyceollin that is produced in elicited soy. Sensitive and specific in vitro bioassays were used to determine that glycinol exhibits potent estrogenic activity. Estrogen-based reporter assays were performed, and glycinol displayed a marked estrogenic effect on estrogen receptor (ER) signaling between 1 and 10 microM, which correlated with comparable colony formation of MCF-7 cells at 10 microM. Glycinol also induced the expression of estrogen-responsive genes (progesterone receptor and stromal-cell-derived factor-1). Competitive binding assays revealed a high affinity of glycinol for both ER alpha (IC(50) = 13.8 nM) and ER beta (IC(50) = 9.1 nM). In addition, ligand receptor modeling (docking) studies were performed and glycinol was shown to bind similarly to both ER alpha and ER beta. Taken together, these results suggest for the first time that glycinol is estrogenic and may represent an important component of the health effects of soy-based foods.

Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A.

We recently completed the total synthesis of spiruchostatin A, a depsipeptide natural product with close structural similarities to FK228, a histone deacetylase (HDAC) inhibitor (HDI) currently being evaluated in clinical trials for cancer. Here we report a detailed characterisation of the in vitro activity of spiruchostatin A. Spiruchostatin A was a potent (sub-nM) inhibitor of class I HDAC activity in vitro and acted as a prodrug, requiring reduction for activity. Spiruchostatin A was a potent (low nM) inhibitor of the growth of various cancer cell lines. Spiruchostatin A-induced acetylation of specific lysine residues within histones H3 and H4, and increased the expression of p21(cip1/waf1), but did not induce acetylation of alpha-tubulin. Spiruchostatin A also induced cell cycle arrest, differentiation and cell death in MCF7 breast cancer cells. Like FK228, spiruchostatin A was both an inducer and substrate of the ABCB1 drug efflux pump. Whereas spiruchostatin A and FK228-induced protracted histone acetylation, hydroxamate HDI-induced short-lived histone acetylation. Using a subset of HDI-target genes identified by microarray analysis, we demonstrated that these differences in kinetics of histone acetylation between HDI correlated with differences in the kinetics of induction or repression of specific target genes. Our results demonstrate that spiruchostatin A is a potent inhibitor of class I HDACs and anti-cancer agent. Differences in the kinetics of action of HDI may be important for the clinical application of these compounds.