Lap. Nissen fundoplication leads to better respiratory symptom control than Toupet in the long term of 20 years.

INTRODUCTION: Having performed anti-reflux surgery for thirty years, it was important to reexamine our patients in the long term to enlarge the body of evidence concerning classical and extraesophageal symptoms that are differently controlled by Nissen or Toupet fundoplication. OBJECTIVES: We report a cohort of 155 GERD patients who underwent fundoplication within a tailored approach between 1994 and 2000. Changes in the perioperative functional outcome, GERD symptoms, and quality of life are being analyzed 10 and 20 years after the operation. RESULTS: The operation resulted in a superior quality of life compared to a patient cohort treated with PPI therapy. We found that both surgical methods (laparoscopic Nissen fundoplication and laparoscopic Toupet fundoplication) cure classical symptoms equally (heartburn, regurgitation, and dysphagia). GERD patients receiving a Toupet fundoplication seem more likely to suffer from extraesophageal GERD symptoms 10 and 20 years after surgery than patients with a Nissen fundoplication. On the other hand, some patients with Nissen fundoplication report dysphagia even 10 and 20 years after surgery. CONCLUSION: Both the laparoscopic Nissen and Toupet fundoplications provide excellent symptom control in the long term. Moreover, the Nissen fundoplication seems to be superior in controlling extraesophageal reflux symptoms, but at the expense of dysphagia. In summary, tailoring the operation based on symptoms seems advantageous.

Linear or circular: Anastomotic ulcer after gastric bypass surgery.

BACKGROUND: After laparoscopic Gastric Bypass Procedure (GBP), anastomotic ulcers (AU) at the gastrojejunostomy (GJ) occur in up to 16% of the patients. Surgical techniques seem to influence the development of AU, but this is still a matter of discussion. This study aims to compare the incidence of AU in circular-stapled (CS) versus linear-stapled (LS) gastrojejunostomy. METHODS: Single-centre retrospective analysis of 241 (m 77 /f 164) consecutive patients (126 CS, 115 LS) with primary or revisional GBP including Roux-Y-Gastric Bypass (RYGB) and One-Anastomosis Gastric Bypass (OAGB) between 01/2014 and 01/2018. Follow-up with oesophagogastroduodenoscopy was only performed in symptomatic patients. Age, body mass index (BMI), comorbidities, smoking and medication were analyzed in both groups. The data are reported as total numbers (%) and mean ± standard deviation. RESULTS: AU occurred significantly more often in the CS group than in the LS group (p = 0.0034). Moreover, refractory AU and the need for revisional surgery were higher in the CS group. Smoking correlates significantly with the development of AU, whereas other risk factors had no impact on its incidence. CONCLUSION: Linear-stapled gastrojejunostomy with a long and narrow pouch should be the preferable procedure for reducing AU development risk. Smoking cessation minimizes the risk for AU and is a necessary part of the treatment.

Arterial Hypertension as a Risk Factor for Reduced Glomerular Filtration Rate after Living Kidney Donation.

Living kidney donation represents the optimal renal replacement therapy, but recent data suggest an increased long-term renal risk for the donor. Here, we evaluated the risk for reduced estimated glomerular filtration rate (eGFR), death, and major cardiovascular events such as nonfatal myocardial infarction or cerebrovascular event including TIA (transient ischemic attack) and stroke in 225 donors, who underwent pre-donation examinations and live donor nephrectomy between 1985 and 2014 at our center. The median follow-up time was 8.7 years (1.0-29.1). In multivariate analysis, age and arterial hypertension at baseline were significantly associated with a higher risk of adverse renal outcomes, such as (1) eGFR <60 mL/min/1.73 m2 (age per year: HR (hazard ratio) 1.05, 95% confidence interval (CI) 1.03-1.08, hypertension: HR 2.25, 95% CI 1.22-3.98), (2) eGFR <60 mL/min/1.73 m2 and a decrease of ≥40% from baseline (age: HR 1.08, 95% CI 1.03-1.13, hypertension: HR 4.22, 95% CI 1.72-10.36), and (3) eGFR <45 mL/min/1.73 m2 (age: HR 1.12, 95% CI 1.05-1.20, hypertension: HR 5.06, 95% CI 1.49-17.22). In addition, eGFR at time of donation (per mL/min/1.73 m2) was associated with a lower risk of (1) eGFR <60 mL/min/1.73 m2 (HR 0.98, 95% CI 0.97-1.00) and (2) eGFR <45 mL/min/1.73 m2 (HR 0.95, 95% CI 0.90-1.00). Age was the only significant predictor for death or major cardiovascular event (HR 1.08, 95% CI 1.01-1.16). In conclusion, arterial hypertension, lower eGFR, and age at the time of donation are strong predictors for adverse renal outcomes in living kidney donors.

Colloidal crystals of compliant microgel beads to study cell migration and mechanosensitivity in 3D.

Tissues are defined not only by their biochemical composition, but also by their distinct mechanical properties. It is now widely accepted that cells sense their mechanical environment and respond to it. However, studying the effects of mechanics in in vitro 3D environments is challenging since current 3D hydrogel assays convolve mechanics with gel porosity and adhesion. Here, we present novel colloidal crystals as modular 3D scaffolds where these parameters are principally decoupled by using monodisperse, protein-coated PAAm microgel beads as building blocks, so that variable stiffness regions can be achieved within one 3D colloidal crystal. Characterization of the colloidal crystal and oxygen diffusion simulations suggested the suitability of the scaffold to support cell survival and growth. This was confirmed by live-cell imaging and fibroblast culture over a period of four days. Moreover, we demonstrate unambiguous durotactic fibroblast migration and mechanosensitive neurite outgrowth of dorsal root ganglion neurons in 3D. This modular approach of assembling 3D scaffolds from mechanically and biochemically well-defined building blocks allows the spatial patterning of stiffness decoupled from porosity and adhesion sites in principle and provides a platform to investigate mechanosensitivity in 3D environments approximating tissues in vitro.

Disease Recurrence-The Sword of Damocles in Kidney Transplantation for Primary Focal Segmental Glomerulosclerosis.

A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell depleting antibodies are effective in recurrent FSGS. This indicates, that the secretion and/or activity of the postulated circulating permeability factor(s) may be B-cell related. This review summarizes the current knowledge on permeability factor(s) possibly related to the disease and discusses strategies for the management of recurrent FSGS. These include profound B-cell depletion prior to transplantation, as well as the salvage of an allograft affected by recurrent FSGS by transfer into a second recipient.

3D Microenvironment Stiffness Regulates Tumor Spheroid Growth and Mechanics via p21 and ROCK.

The mechanical properties of cancer cells and their microenvironment contribute to breast cancer progression. While mechanosensing has been extensively studied using 2D substrates, much less is known about it in a physiologically more relevant 3D context. Here it is demonstrated that breast cancer tumor spheroids, growing in 3D polyethylene glycol-heparin hydrogels, are sensitive to their environment stiffness. During tumor spheroid growth, compressive stresses of up to 2 kPa build up, as quantitated using elastic polymer beads as stress sensors. Atomic force microscopy reveals that tumor spheroid stiffness increases with hydrogel stiffness. Also, constituent cell stiffness increases in a Rho associated kinase (ROCK)- and F-actin-dependent manner. Increased hydrogel stiffness correlated with attenuated tumor spheroid growth, a higher proportion of cells in G0/G1 phase, and elevated levels of the cyclin-dependent kinase inhibitor p21. Drug-mediated ROCK inhibition not only reverses cell stiffening upon culture in stiff hydrogels but also increases tumor spheroid growth. Taken together, a mechanism by which the growth of a tumor spheroid can be regulated via cytoskeleton rearrangements in response to its mechanoenvironment is revealed here. Thus, the findings contribute to a better understanding of how cancer cells react to compressive stress when growing under confinement in stiff environments.

Laparoscopic Adjustable Gastric Banding: an Underestimated Risk Factor for the Development of Esophageal Cancer?-a Nationwide Survey.

BACKGROUND: Approximately 14% of Austria's 8.5 million inhabitants have a body mass index (BMI) > 30 kg/m2. The laparoscopic adjustable gastric banding (LAGB) was introduced in Austria in 1994, where about 10.300 patients have received it so far. One of our LAGB patients developed an adenocarcinoma of the distal esophagus 13 years after implantation. OBJECTIVES: In order to calculate whether after LAGB patients are at higher risk for carcinoma of the esophagus, we performed a nationwide survey. METHODS: A questionnaire was sent to all surgical departments in Austria, primarily in order to detect cases with esophageal carcinoma after LAGB, but also to evaluate the policy in Austria concerning preoperative work-up, operation, and follow-up in LAGB patients. RESULTS: Since 1994, 37 of the 119 surgical departments in Austria have performed a total of about 10.300 LAGB implantations. Six patients have been identified with esophageal cancer following LAGB. The WHO statistical report on esophageal cancer shows an incidence of 2.8/100.000 per year in Austria, about 1/3 of which cases are adenocarcinoma of the distal esophagus. CONCLUSION: Following LAGB, the incidence of esophageal cancer might be up to fivefold higher than the aged standardized overall population of Austria.

Successful management of recurrent focal segmental glomerulosclerosis.

Primary focal segmental glomerulosclerosis (FSGS) recurs in up to 55% of patients after kidney transplantation. Herein we report the successful management of recurrent FSGS. A 5-year-old boy with primary FSGS received a deceased donor renal transplant. Immediate and fulminant recurrence of FSGS caused anuric graft failure that was resistant to plasmapheresis and rituximab. After exclusion of structural or immunologic damage to the kidney by repeated biopsies, the allograft was retrieved from the first recipient on day 27 and transplanted into a 52-year-old second recipient who had vascular nephropathy. Immediately after retransplantation, the allograft regained function with excellent graft function persistent now at 3 years after transplant. After 2 years on hemodialysis, the boy was listed for kidney retransplantation. To prevent FSGS recurrence, pretreatment with ofatumumab was performed. Nephrotic range proteinuria still occurred after the second transplantation, which responded, however, to daily plasma exchange in combination with ofatumumab. At 8 months after kidney retransplantation graft function is good. The clinical course supports the hypothesis of a circulating permeability factor in the pathogenesis of FSGS. Successful ofatumumab pretreatment implicates a key role of B cells. Herein we provide a description of successful management of kidney failure by FSGS, carefully avoiding waste of organs.

Real-time fluorescence and deformability cytometry.

The throughput of cell mechanical characterization has recently approached that of conventional flow cytometers. However, this very sensitive, label-free approach still lacks the specificity of molecular markers. Here we developed an approach that combines real-time 1D-imaging fluorescence and deformability cytometry in one instrument (RT-FDC), thus opening many new research avenues. We demonstrated its utility by using subcellular fluorescence localization to identify mitotic cells and test for mechanical changes in those cells in an RNA interference screen.

Laparoscopic sleeve gastrectomy: gateway to kidney transplantation.

BACKGROUND: The prevalence of obesity and obesity-related morbidity in end-stage renal disease patients is rising. Although it is established that obesity does not abrogate the transplant benefit with respect to lower long-term mortality and cardiovascular risk, it is associated with increased graft failure, delayed graft function, surgical complications, prolonged hospital stay, and costs. OBJECTIVES: To examine the safety and efficacy of LSG (laparoscopic sleeve gastrectomy) in renal transplant candidates and evaluate transplant outcomes. SETTING: Single-center prospective nonrandomized trial METHODS: We here report on a prospective single-center trial establishing a 2-step approach for obese renal transplant candidates. Patients with end-stage renal disease and a BMI (body mass index) of 35 kg/m2 or higher underwent laparoscopic sleeve gastrectomy. After reaching a BMI of<35 kg/m2, patients were waitlisted for kidney transplantation. Age, gender, body mass index (BMI), associated co-morbidities, cause of end-stage renal disease, surgical complications, and outcome after kidney transplantation (graft survival, incidence of delayed graft function, incidence of rejection, serum creatinine) were collected. RESULTS: LSG was performed in 8 renal transplant candidates with a mean BMI of 38.8 kg/m2 each. BMI dropped to below 35 kg/m2 within a median of 3 months. Percent excess body mass index loss (%EBMIL) was 62.7% at 1 year after LSG. Within 17 months (mean) after metabolic surgery, 7 patients underwent kidney transplantation. All transplants were successful with a serum creatinine of 1.9±.8 mg/dL at discharge and stable allograft function thereafter. Mean follow-up was 3.2±1.4 years; no patient was lost to follow-up. CONCLUSION: LSG is safe and efficacious for treatment of obesity in renal transplant candidates. Rapid and sustained weight loss and subsequent waitlisting for kidney transplantation may reduce overall and in particular posttransplant patient morbidity.

Next generation gene synthesis: From microarrays to genomes.

Similar to the incredible advances in DNA sequencing, the de novo synthesis of DNA is subject to innovations and fast progress in terms of synthesis speed and cost. We will discuss novel techniques that are expected to enable high-throughput synthesis of oligonucleotides on microarrays and the subsequent assembly into longer fragments, up to whole genomes. Especially, the inherent disadvantages of microarray-derived oligonucleotide pools for gene synthesis will be discussed in detail, and also the different approaches to still render these oligonucleotides useful for gene assembly. These so-called next-generation techniques will lead to a significant cost reduction of gene synthesis and to the possibility of much larger projects, such as whole genome synthesis.

Comparing routine administrative data with registry data for assessing quality of hospital care in patients with myocardial infarction using deterministic record linkage.

BACKGROUND: Assessment of quality of care in patients with myocardial infarction (MI) should be based on data that effectively enable determination of quality. With the need to simplify measurement techniques, the question arises whether routine data can be used for this purpose. We therefore compared data from a German sickness fund (AOK) with data from the Berlin Myocardial Infarction Registry (BMIR). METHODS: We included patients hospitalised for treatment of MI in Berlin from 2009-2011. We matched 2305 patients from AOK and BMIR by using deterministic record linkage with indirect identifiers. For matched patients we compared the frequency in documentation between AOK and BMIR for quality assurance variables and calculated the kappa coefficient (KC) as a measure of agreement. RESULTS: There was almost perfect agreement in documentation between AOK and BMIR data for matched patients for: catheter laboratory (KC: 0.874), ST elevation MI (KC: 0.826), diabetes (KC: 0.818), percutaneous coronary intervention (KC: 0.860) and hospital mortality (KC: 0.952). The remaining variables compared showed moderate or less than moderate agreement (KC < 0.6), and were grouped in Category II with less frequent documentation in AOK for risk factors and aspects of patients' history; in Category III with more frequent documentation in AOK for comorbidities; and in Category IV for medication at and after hospital discharge. CONCLUSIONS: Routine data are primarily collected and defined for reimbursement purposes. Quality assurance represents merely a secondary use. This explains why only a limited number of variables showed almost perfect agreement in documentation between AOK and BMIR. If routine data are to be used for quality assessment, they must be constantly monitored and further developed for this new application. Furthermore, routine data should be complemented with registry data by well-established methods of record linkage to realistically reflect the situation - also for those quality-associated variables not collected in routine data.

Brainstem Tuberculoma in Pregnancy.

We report a case of a Somali refugee who presented in the second trimester of her first pregnancy with a four-week history of gradual right-sided sensomotoric hemisyndrome including facial palsy and left-sided paresis of the oculomotorius nerve causing drooping of the left eyelid and double vision. Cranial magnetic resonance imaging revealed a solitary brainstem lesion. Upon detection of hilar lymphadenopathy on chest X-ray (CXR), the diagnosis of disseminated tuberculosis with involvement of the central nervous system was confirmed by PCR and treatment induced with rifampicin, isoniazid, pyrazinamide, and ethambutol. The patient had a steady neurological improvement and a favorable pregnancy outcome.

Branchfall as a Demographic Filter for Epiphyte Communities: Lessons from Forest Floor-Based Sampling.

Local variation in the abundance and richness of vascular epiphytes is often attributed to environmental characteristics such as substrate and microclimate. Less is known, however, about the impacts of tree and branch turnover on epiphyte communities. To address this issue, we surveyed branches and epiphytes found on the forest floor in 96 transects in two forests (Atlantic rainforest in Brazil and Caribbean rainforest in Panama). In the Brazilian forest, we additionally distinguished between edge and core study sites. We quantified branch abundance, epiphyte abundance, richness and proportion of adults to investigate the trends of these variables over branch diameter. Branches <2 cm in diameter comprised >90% of all branches on the forest floor. Abundance and richness of fallen epiphytes per transect were highest in the Brazilian core transects and lowest in the Panamanian transects. The majority of epiphytes on the floor (c. 65%) were found attached to branches. At all three study sites, branch abundance and branch diameter were negatively correlated, whereas epiphyte abundance and richness per branch, as well as the proportion of adults were positively correlated with branch diameter. The relationship between branch diameter and absolute epiphyte abundance or richness differed between study sites, which might be explained by differences in forest structure and dynamics. In the Panamanian forest, epiphytes had been previously inventoried, allowing an evaluation of our surveying method by comparing canopy and forest floor samplings. Individuals found on the forest floor corresponded to 13% of all individuals on branches <10 cm in diameter (including crowns), with abundance, richness and composition trends on forest floor reflecting canopy trends. We argue that forest floor surveys provide useful floristic and, most notably, demographic information particularly on epiphytes occurring on the thinnest branches, which are least accessible. Here, branchfall acts as an important demographic filter structuring epiphyte communities.

Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts.

Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.

Host specificity in vascular epiphytes: a review of methodology, empirical evidence and potential mechanisms.

Information on the degree of host specificity is fundamental for an understanding of the ecology of structurally dependent plants such as vascular epiphytes. Starting with the seminal paper of A.F.W. Schimper on epiphyte ecology in the late 19th century over 200 publications have dealt with the issue of host specificity in vascular epiphytes. We review and critically discuss this extensive literature. The available evidence indicates that host ranges of vascular epiphytes are largely unrestricted while a certain host bias is ubiquitous. However, tree size and age and spatial autocorrelation of tree and epiphyte species have not been adequately considered in most statistical analyses. More refined null expectations and adequate replication are needed to allow more rigorous conclusions. Host specificity could be caused by a large number of tree traits (e.g. bark characteristics and architectural traits), which influence epiphyte performance. After reviewing the empirical evidence for their relevance, we conclude that future research should use a more comprehensive approach by determining the relative importance of various potential mechanisms acting locally and by testing several proposed hypotheses regarding the relative strength of host specificity in different habitats and among different groups of structurally dependent flora.

The role of lipocalin-2 in liver regeneration.

BACKGROUND & AIMS: Various immune mediators such as interleukin-6 (IL-6) have been implicated in the process of liver regeneration. Lipocalin-2 (LCN2) has been recently characterized as a prototypic immune mediator produced by various cell types being involved mainly in host defence. In addition, numerous studies have demonstrated its clinical value as a biomarker. This study aimed at defining the role of LCN2 in liver regeneration. METHODS: We studied LCN2 expression in wild-type mice in a model of partial hepatectomy (PH). Furthermore, we evaluated liver regeneration after PH in LCN-deficient mice compared to littermate controls. Serum levels of LCN2 were assessed in a small group of patients undergoing hepatic resection. RESULTS: LCN2 is dramatically induced in livers and sera of wild-type mice after PH, whereas liver LCN2-receptor expression was decreased. Sham operations did not affect hepatic and serum LCN2 expression. Although LCN2-deficient mice exhibited increased baseline liver expression indices, LCN2-deficient mice did not differ from wild-type mice with respect to hepatic proliferation suggesting that this molecule is not involved in hepatic repair. Only serum IL-1ß levels were slightly lower in LCN(-/-) mice, whereas IL-6 serum levels did not differ between various tested animal groups. In humans undergoing hepatic resection, LCN2 levels increased significantly within 24 h following surgery. CONCLUSIONS: LCN2, although massively induced in mice after PH, is not relevant in murine hepatic regeneration. Further, human studies have to define whether LCN2 could evolve as biomarker after liver surgery.

Proteomics in transplantation.

Proteomics and biochemical profiling have emerged as exciting and powerful tools in clinical biomarker research. In the field of transplantation, proteomics aims not only at developing noninvasive means for immune monitoring but also to gain mechanistic insights into the pathophysiology of the alloimmune response and hence defining new therapeutic targets. This chapter provides an overview of proteomic biomarker-driven approaches and its underlying concepts and discusses the advantages, clinical implications, challenges, and limitations of this novel modality as it relates to solid organ transplantation.