Flexible endoscopy is enough diagnostic prior to loop ileostomy reversal.

PURPOSE: This study investigates whether contrast enema (CE) and flexible endoscopy (FE) should be performed routinely after low anterior resection (LAR) before ileostomy reversal. Additionally, the impact of previous anastomotic leakage (AL) on diagnostic test accuracy (DTA) was assessed. METHODS: This is a retrospective analysis of prospectively collected tertiary care data of two centers. Consecutive rectal cancer patients undergoing LAR with loop ileostomy formation were included. Before ileostomy reversal, all patients were assessed by CE and FE. DTA of FE and CE for asymptomatic AL in patients who had previously suffered from clinically relevant AL (group 1) compared with those without apparent AL after LAR (group 0) were assessed separately. RESULTS: Two hundred ninety-three patients were included in the analysis, 86 in group 1 and 207 in group 0. Overall sensitivity for detection of asymptomatic AL was 76% (FE) and 60% (CE). Specificity was 100% for both tests. DTA of FE was equal or superior to CE in all subgroups. Prevalence of asymptomatic AL at the time of testing was 1.4% in group 0 and 25.6% in group 1. CONCLUSION: Flexible endoscopy is the more accurate diagnostic test for the detection of asymptomatic anastomotic leaks prior to ileostomy reversal. Contrast enema showed no gain of information. In the group without complications after the initial rectal resection, 104 must be tested to find one leak prior to reversal. In those patients, routine diagnostic testing additional to digital rectal examination may be questioned.

Handgrip Strength and Phase Angle Predict Outcome After Bariatric Surgery.

BACKGROUND: The amount of postoperative weight loss after bariatric surgery varies interindividually. The quality of the pre- and postoperative body composition is an important predictor of success. The aim of this study was to investigate the role of preoperative handgrip strength and phase angle (PhA) as predictors of sustained postoperative weight loss in order to assess the influence of body composition on the postoperative outcome after bariatric surgery. METHOD: In a prospective cohort study, bioelectrical impedance and follow-up data of 198 patients after laparoscopic sleeve gastrectomy (SG; n = 68) and Roux-en-Y gastric bypass (GB; n = 130) were analyzed for a period of 36 months postoperatively. RESULTS: The mean preoperative handgrip strength (31.48 kg, SD 9.97) correlates significantly with the postoperative body composition up to 24 months after surgery. Preoperative PhA, gender, size, and body weight influenced postoperative weight loss significantly. A significant correlation between preoperative PhA (mean 6.18°, SD 0.89°) and total weight loss (%TWL) was observed up to 3 months after SG (r = 0.31444, p = 0.0218) and up to 12 months after GB (r = 0.19184, p = 0.0467). The optimum cutoff for the prediction of a response of less than 50% excess weight loss was a preoperative PhA of 6.0°. CONCLUSIONS: The preoperative handgrip strength confirmed its suitability for use as a predictor of postoperative body composition, whereas the preoperative PhA predicts postoperative weight loss after bariatric surgery. Further research is necessary to identify the role of these parameters for preconditioning.

Incisional hernia rate after ileostomy closure in lateral pararectal stoma versus transrectal stoma placement: follow-up of the randomized PATRASTOM trial.

AIM: Because damage to the rectus abdominis muscle during ileostomy placement and reversal might be a risk factor for the development of stoma-site incisional hernia (SSIH), we hypothesized that positioning of the stoma lateral to the rectus abdominis muscle might prevent SSIH. METHOD: To investigate whether a lateral pararectal stoma position lowers the incidence of SSIH in comparison with a transrectal position, a follow-up study of the PATRASTOM trial, which had randomized stoma placement (lateral pararectal versus transrectal), was conducted. All former participants were invited simultaneously for a follow-up visit in September 2016, 2 years after database closure of the PATRASTOM trial. For patients who were not able to attend the follow-up, the electronic chart as well as MRI/CT scans were reviewed with regard to the presence of SSIH. RESULTS: Follow-up - either clinical or radiological - was available for 47 of the 60 PATRASTOM participants. The median duration of follow-up was 3.4 years (interquartile range 3.0-4.1 years). SSIH occurred in 3 of 23 patients (13.0%) in the lateral pararectal group compared with 7 of 24 patients (29.2%) in the transrectal group (P = 0.287). Four of the 10 patients diagnosed with SSIH had already undergone or were scheduled for hernia repair. Of the patient and procedure characteristics which may have an impact on the development of incisional hernia none was a significant risk factor for SSIH. CONCLUSION: In the present follow-up study, no difference in the incidence of SSIH was found between lateral pararectal and transrectal stoma construction in an elective setting.

[The Kono-S anastomosis in surgery for Crohn's disease : First results of a new functional end-to-end anastomotic technique after intestinal resection in patients with Crohn's disease in Germany]. / Die Kono-S-Anastomose in der Chirurgie des Morbus Crohn : Erste Ergebnisse einer neuen, funktionellen End-zu-End-Anastomosentechnik nach intestinaler Resektion bei Patienten mit Morbus Crohn in Deutschland.

BACKGROUND: Recurrent disease at the anastomotic site after bowel resection represents a major problem in patients with Crohn's disease. In 2011, a new anastomotic technique (Kono-S anastomosis) was published, which as a functional end-to-end anastomosis creating a wide anastomotic diameter aimed to reduce the rate of recurrence after surgery. AIM: To evaluate the Kono-S anastomosis with respect to early and late postoperative complications and recurrence rate after surgical intestinal resection in patients with Crohn's disease at a university center. PATIENTS AND METHODS: All patients with Crohn's disease who underwent Kono-S anastomoses between June 2015 and December 2016 at the Department of Surgery, University Medical Centre Mannheim, were included in the study. After obtaining informed consent, patient data regarding surgery and hospital stay were recorded in a prospective database. Follow-up was carried out by structured telephone interviews including disease progression, medication and surveillance. Statistical analysis was performed using the Graph Pad Prism 7 software. Ethics board approval was obtained from the Medical Ethics Commission II of the Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (No. 2017-575N-MA). RESULTS: A total of 53 patients (32 female and 21 male) were included in this study. The median procedural time was 157 min. The median follow-up was 12 months (range 4-23 months). Of the patients 3 developed early postoperative complications with a Clavien-Dindo score ≥ III and 25 patients with or without symptoms were controlled by endoscopy and/or magnetic resonance imaging (MRI) and no anastomotic recurrence was detected. No endoscopic interventions were necessary and 16 patients were symptom-free with no further specific therapy or controls. DISCUSSION: The Kono-S anastomosis is a safe anastomotic method with low morbidity. In the early follow-up recurrence rates of Crohn's disease at the anastomotic site were low. In the literature a reoperation rate of 5 % per year is given for patients with Crohn's disease after intestinal resection, so that in the long-term observation a valid statement on recurrence rate is possible. A potential advantage of the morphological end-to-end configuration of the Kono-S anastomosis is the better endoscopic dilatation compared to a side-to-side anastomosis. CONCLUSION: The Kono-S anastomotic technique has a low morbidity. In the early follow-up observational period no recurrence occurred in the anastomosis area in this series. Long-term data must clarify whether this technique is advantageous with respect to this aspect in the long run.

A pilot single-centre randomized trial assessing the safety and efficacy of lateral pararectus abdominis compared with transrectus abdominis muscle stoma placement in patients with temporary loop ileostomies: the PATRASTOM trial.

AIM: Transrectal stoma placement is considered the standard technique for positioning a stoma. A prospective series using a novel method of lateral pararectal stoma placement recently revealed a remarkably low stoma herniation rate. A randomized trial was conducted to compare the lateral pararectal with the transrectal stoma position with regard to parastomal herniation, stoma-related morbidity and quality of life. METHOD: Adult patients undergoing elective placement of a temporary loop ileostomy were eligible for inclusion. Patients were intra-operatively randomized to undergo either a lateral pararectal or a transrectal ileostomy. The primary end-point was the rate of parastomal herniation. Secondary end-points included other stoma-related complications and quality of life. Sample size calculation resulted in 54 patients having to be analysed to detect a difference of parastomal herniation of 30% with an 80% power and a 5% significance level. The trial was registered with the German Clinical Trials Register (registration number DRKS00003534). RESULTS: Between April 2012 and April 2014, 30 patients were randomized to each group. The incidence of parastomal herniation did not differ between the lateral pararectal (5 of 27) and the transrectal group (4 of 29; P = 0.725). There was also no significant difference regarding other stoma-related complications and the EORTC quality of life scales C30 and CR29. CONCLUSION: The incidence of parastomal herniation and other stoma-related complications did not differ between the groups. However, due to the limited sample size a small difference in favour of one of the two stoma placement techniques cannot be entirely ruled out.

Simultaneous Raman microspectroscopy and fluorescence imaging of bone mineralization in living zebrafish larvae.

Confocal Raman microspectroscopy and fluorescence imaging are two well-established methods providing functional insight into the extracellular matrix and into living cells and tissues, respectively, down to single molecule detection. In living tissues, however, cells and extracellular matrix coexist and interact. To acquire information on this cell-matrix interaction, we developed a technique for colocalized, correlative multispectral tissue analysis by implementing high-sensitivity, wide-field fluorescence imaging on a confocal Raman microscope. As a proof of principle, we study early stages of bone formation in the zebrafish (Danio rerio) larvae because the zebrafish has emerged as a model organism to study vertebrate development. The newly formed bones were stained using a calcium fluorescent marker and the maturation process was imaged and chemically characterized in vivo. Results obtained from early stages of mineral deposition in the zebrafish fin bone unequivocally show the presence of hydrogen phosphate containing mineral phases in addition to the carbonated apatite mineral. The approach developed here opens significant opportunities in molecular imaging of metabolic activities, intracellular sensing, and trafficking as well as in vivo exploration of cell-tissue interfaces under (patho-)physiological conditions.

Omalizumab in patients with severe persistent allergic asthma in a real-life setting in Germany.

Omalizumab is a humanized monoclonal anti-immunoglobulin E (IgE) antibody indicated in Europe for the treatment of uncontrolled severe persistent allergic (IgE-mediated) asthma despite optimal therapy with inhaled corticosteroids and long-acting beta(2) agonists. Between 2005 and 2007 280 patients (58% female, mean age 44+/-16 yrs., 46% on oral corticosteroids, median serum IgE level 235IU/ml) who met the EU criteria for add-on therapy with anti-IgE were treated prospectively with omalizumab by 134 physicians as part of a post-marketing surveillance trial and were followed-up for 6 months. The median follow-up time was 195 days, the patients were treated with a median dose of 450mg omalizumab every 4 weeks. After 6 months there was a marked effect of omalizumab treatment on daily (-76%) and nocturnal symptoms (-84%), exacerbations (-82%), unscheduled health care contacts (-81%), hospitalizations (-78%) and quality of life (Mini-AQLQ: score increase from 2.9 to 4.5). Overall, efficacy of omalizumab was rated as excellent or good by the majority of physicians (82%) and patients (86%). In 19 patients (7%) omalizumab-related adverse events were recorded. This post-marketing surveillance trial confirms the marked and clinically relevant effect of omalizumab on asthma symptoms and level of asthma control in the majority of patients with severe persistent allergic (IgE-mediated) asthma in a real-life situation.

Combination of omalizumab and specific immunotherapy is superior to immunotherapy in patients with seasonal allergic rhinoconjunctivitis and co-morbid seasonal allergic asthma.

BACKGROUND: The treatment of allergic asthma by specific immunotherapy (SIT) is hampered by potential side-effects. OBJECTIVE: The aim of this study was to study the effect of omalizumab, a monoclonal anti-IgE antibody, in combination with SIT in patients with seasonal allergic rhinoconjunctivitis (SAR) and co-morbid seasonal allergic asthma (SAA) incompletely controlled by conventional pharmacotherapy. METHODS: A randomized, double-blind, placebo-controlled, multi-centre trial was performed to assess the efficacy and safety of omalizumab (Xolair) vs. placebo in combination with depigmented SIT (Depigoid) during the grass pollen season. Omalizumab or placebo was started 2 weeks before SIT; the whole treatment lasted 18 weeks. Primary endpoint was daily 'symptom load', the sum of daily scores for symptom severity and rescue medication use. RESULTS: A total of 140 patients (age 11-46 years) were randomized; and a total of 130 finished the study. Combination therapy reduced the symptom load by 39% (P=0.0464, Wilcoxon test) over SIT monotherapy. This difference was mainly due to reduced symptom severity (P=0.0044), while rescue medication use did not change significantly. Combination therapy also improved asthma control (Asthma Control Questionnaire, P=0.0295) and quality of life in the case of asthma (Asthma Quality of Life Questionnaire, P=0.0293) and rhinoconjunctivitis (Rhinoconjunctivitis Quality of Life Questionnaire, P=0.0537). Numbers of patients with 'excellent or good' treatment efficacy according to ratings of investigators (75.0% vs. 36.9%) or patients (78.5% vs. 46.1%) were markedly higher in the combination group than under SIT alone. CONCLUSION: Combination of omalizumab with SIT for treatment of patients with SAR and co-morbid SAA was safe and reduced the symptom load in a statistically significant and clinically meaningful manner.

Bazooka and atypical protein kinase C are required to regulate oocyte differentiation in the Drosophila ovary.

The par genes, identified by their role in the establishment of anterior-posterior polarity in the Caenorhabditis elegans zygote, subsequently have been shown to regulate cellular polarity in diverse cell types by means of an evolutionarily conserved protein complex including PAR-3, PAR-6, and atypical protein kinase C (aPKC). The Drosophila homologs of par-1, par-3 (bazooka, baz), par-6 (DmPar-6), and pkc-3 (Drosophila aPKC, DaPKC) each are known to play conserved roles in the generation of cell polarity in the germ line as well as in epithelial and neural precursor cells within the embryo. In light of this functional conservation, we examined the potential role of baz and DaPKC in the regulation of oocyte polarity. Our analyses reveal germ-line autonomous roles for baz and DaPKC in the establishment of initial anterior-posterior polarity within germ-line cysts and maintenance of oocyte cell fate. Germ-line clonal analyses indicate both proteins are essential for two key aspects of oocyte determination: the posterior translocation of oocyte specification factors and the posterior establishment of the microtubule organizing center within the presumptive oocyte. We demonstrate BAZ and DaPKC colocalize to belt-like structures between germarial cyst cells. However, in contrast to their regulatory relationship in the Drosophila and C. elegans embryos, these proteins are not mutually dependent for their germ-line localization, nor is either protein specifically required for PAR-1 localization to the fusome. Therefore, whereas BAZ, DaPKC, and PAR-1 are functionally conserved in establishing oocyte polarity, the regulatory relationships among these genes are not well conserved, indicating these molecules function differently in different cellular contexts.

spiel ohne grenzen/pou2 is required during establishment of the zebrafish midbrain-hindbrain boundary organizer.

The vertebrate midbrain-hindbrain boundary (MHB) organizes patterning and neuronal differentiation in the midbrain and anterior hindbrain. Formation of this organizing center involves multiple steps, including positioning of the MHB within the neural plate, establishment of the organizer and maintenance of its regional identity and signaling activities. Juxtaposition of the Otx2 and Gbx2 expression domains positions the MHB. How the positional information is translated into activation of Pax2, Wnt1 and Fgf8 expression during MHB establishment remains unclear. In zebrafish spiel ohne grenzen (spg) mutants, the MHB is not established, neither isthmus nor cerebellum form, the midbrain is reduced in size and patterning abnormalities develop within the hindbrain. In spg mutants, despite apparently normal expression of otx2, gbx1 and fgf8 during late gastrula stages, the initial expression of pax2.1, wnt1 and eng2, as well as later expression of fgf8 in the MHB primordium are reduced. We show that spg mutants have lesions in pou2, which encodes a POU-domain transcription factor. Maternal pou2 transcripts are distributed evenly in the blastula, and zygotic expression domains include the midbrain and hindbrain primordia during late gastrulation. Microinjection of pou2 mRNA can rescue pax2.1 and wnt1 expression in the MHB of spg/pou2 mutants without inducing ectopic expression. This indicates an essential but permissive role for pou2 during MHB establishment. pou2 is expressed normally in noi/pax2.1 and ace/fgf8 zebrafish mutants, which also form no MHB. Thus, expression of pou2 does not depend on fgf8 and pax2.1. Our data suggest that pou2 is required for the establishment of the normal expression domains of wnt1 and pax2.1 in the MHB primordium.

Positional cloning of heart and soul reveals multiple roles for PKC lambda in zebrafish organogenesis.

BACKGROUND: The Par-3/Par-6/aPKC complex is a key regulator of cell polarity in a number of systems. In Drosophila, this complex acts at the zonula adherens (adherens junctions) to establish epithelial polarity and helps to orient the mitotic spindle during asymmetric neuroblast divisions. In MDCKII cells, this complex localizes to the zonula occludens (tight junctions) and appears to regulate epithelial polarity. However, the in vivo role of this complex during vertebrate embryogenesis is not known, due to the lack of relevant mutations. RESULTS: We have positionally cloned the zebrafish heart and soul (has) mutation, which affects the morphogenesis of several embryonic tissues, and show that it encodes atypical protein kinase C lambda (aPKC lambda). We find that loss of aPKC lambda affects the formation and maintenance of the zonula adherens in the polarized epithelia of the retina, neural tube, and digestive tract, leading to novel phenotypes, such as the formation of multiple lumens in the developing intestine. In addition, has mutants display defects in gut looping and endodermal organ morphogenesis that appear to be independent of the defects in epithelial polarity. Finally, we show that loss of aPKC lambda leads to defects in spindle orientation during progenitor cell divisions in the neural retina. CONCLUSIONS: Our results show that aPKC lambda is required for the formation and maintenance of the zonula adherens during early epithelial development in vertebrates and demonstrate a previously undescribed yet critical role for this protein in organ morphogenesis. Furthermore, our studies identify the first genetic locus regulating the orientation of cell division in vertebrates.

A gain-of-function screen for genes that affect the development of the Drosophila adult external sensory organ.

The Drosophila adult external sensory organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in sensory organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rorth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external sensory organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external sensory organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external sensory organs or subsets of sensory organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system.

Academic achievement of African American preadolescents: the influence of teacher perceptions.

The purpose of this study was to identify the factors associated with the academic success of predominantly, middle-class African American preadolescent students. This study proposed an ecological model that considered the interaction of family environment, teacher perceptions of social skills, and student characteristics. The estimated model explained 58% of the variance in grade point average. Path analysis revealed three direct effects on grade point average, (a) grade level (negative), (b) teacher perceptions of social skills, and (c) academic ability. Findings revealed that teacher perceptions of social skills was a stronger predictor of grade point average than academic ability. Two indirect effects on grade point average were found. The first indirect effect was negative: gender predicted academic ability, which predicted teacher perceptions of social skills, which predicted grade point average. The second indirect effect was positive and it was from ability to teacher perceptions to grade point average. Implications for policy and practice are made that suggest a collaborative model of school counseling designed to "promote" the social and academic competence of African American students. Interventions that enhance teacher practices are also suggested.