Functional outcome after laparoscopic and open incisional hernia repair

Abstract: Background: The debate about the advantages of laparoscopic versus open incisional hernia repair is still ongoing. The primary outcomes of already published studies are mainly recurrence, pain and quality of life. Data on postoperative abdominal wall function after these corrections is still lacking. In this single center study muscle strength and transverse abdominal muscle thickness were analysed with regard to open and laparoscopic techniques. Methods: Thirty-five patients that underwent open and laparoscopic midline incisional hernia correction were included. Approximation of the rectus muscles was included in some open procedures but never in laparoscopic correction. Twelve healthy subjects without any abdominal operation functioned as a control group. Trunk flexion muscle strength of all operated patients and 12 healthy subjects was studied with the Biodex® isokinetic dynamometer and conventional abdominal muscle trainers for the rectus and oblique abdominal muscles. All patients underwent ultrasound examination of the abdominal wall for analysing transverse abdominal muscle thickness. Results: The mean torque/weight (%) for trunk flexion, measured with the Biodex®, was significantly higher in the control compared with the total patient group. Comparing trunk flexion with the Biodex® after either laparoscopic or open incisional hernia repair showed a trend in favour of the open group after adjusting for gender. The muscle strength measured by the conventional abdominal muscle trainers showed no differences between the operation groups. The transverse abdominal muscle thickness difference between rest and contraction was significantly higher in the open repair group. Conclusions: The isokinetic strength of trunk flexor muscles is reduced after an operation for incisional hernia. There is some evidence that open repair with approximation of the rectus abdominis muscles results in higher muscle strength of the rectus muscles and higher thickness differences between res

A new three-step hybrid approach is a safe procedure for incisional hernia: early experiences with a single centre retrospective cohort

Purpose: In this study, a three-step novel surgical technique was developed for incisional hernia, in which a laparoscopic procedure with a mini-laparotomy is combined: so-called ‘three-step incisional hybrid repair’. The aim of this study was to reduce the risk of intestinal lacerations during adhesiolysis and recurrence rate by better symmetrical overlap placement of the mesh. Objectives: To evaluate first perioperative outcomes with this technique. Methods: From 2016 to 2020, 70 patients (65.7% females) with an incisional hernia of > 2 and ≤ 10 cm underwent a elective three-step incisional hybrid repair in two non-academic hospitals performed by two surgeons specialised in abdominal wall surgery. Intra- and postoperative complications, operation time, hospitalisation time and hernia recurrence were assessed. Results: Mean operation time was 100 min. Mean hernia size was 4.8 cm; 45 patients (64.3%) had a hernia of 1–5 cm, 25 patients (35.7%) of 6–10 cm. Eight patients had a grade 1 complication (11.4%), five patients a grade 2 (7.1%), two patients (2.8%) a grade 4 complication and one patient (1.4%) a grade 5 complication. Five patients had an intraoperative complication (7.0%), two enterotomies, one serosa injury, one omentum bleeding and one laceration of an epigastric vessel. Mean length of stay was 3.3 days. Four patients (5.6%) developed a hernia recurrence during a mean follow-up of 19.5 weeks. Conclusion: A three-step hybrid incisional hernia repair is a safe alternative for incisional hernia repair. Intraoperative complications rate was low

Human adrenocorticotropin-secreting pituitary adenomas show frequent loss of heterozygosity at the glucocorticoid receptor gene locus

Corticotropinomas are characterized by a relative resistance to the negative feedback action of cortisol on ACTH secretion. In this respect there is a similarity with the clinical syndrome of cortisol resistance. As cortisol resistance can be caused by genetic abnormalities in the glucocorticoid receptor (GR) gene, we investigated whether the insensitivity of corticotropinomas to cortisol is also caused by de novo mutations in the GR gene. We screened for the GR gene in leukocyte and tumor DNA from 22 patients with Cushing's disease for mutations using PCR/single strand conformation polymorphism analysis. In a previous study, we identified 5 polymorphisms in the GR gene in a normal population. These polymorphisms were used as markers for the possible occurrence of loss of heterozygosity (LOH) at the GR gene locus. Except for 1 silent point mutation, we did not identify novel mutations in the GR gene in leukocytes or corticotropinomas from these patients. Of the 22 patients, 18 were heterozygous for at least 1 of the polymorphisms. In 6 of these patients, LOH had occurred in the tumor DNA. Of 21 patients examined for LOH on chromosome 11q13, only 1, with a corticotroph carcinoma, showed allelic deletion. As controls we studied 28 pituitary tumors of other subtypes (11 clinically nonfunctioning, 8 prolactinomas, and 9 GH-producing adenomas) and found evidence for LOH in only 1 prolactinoma. In six patients LOH was found at the GR gene locus (chromosome 5) in DNA derived from adenoma cells. Our observations indicate for the first time that LOH at the GR gene locus is a relatively frequent phenomenon in pituitary adenomas of patients with Cushing's disease. This might explain the relative resistance of the adenoma cells to the inhibitory feedback action of cortisol on ACTH secretion. The specificity of the GR LOH to corticotropinomas supports this concept. Somatic mutations of the GR are not a frequent cause of relative cortisol resistance in these cells

Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

INTRODUCTION\nDrug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics.\nAREAS COVERED\nIn this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles.\nEXPERT OPINION\nMore scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.Pharmacolog

Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

Search for Higgs bosons of the minimal supersymmetric standard model in p-pbar collisions at sqrt(s)=1.96 TeV

We report results from searches for neutral Higgs bosons produced in p-pbar collisions recorded by the Dzero experiment at the Fermilab Tevatron Collider. We study the production of inclusive neutral Higgs boson in the tautau final state and in association with a b quark in the btautau and bbb final states. These results are combined to improve the sensitivity to the production of neutral Higgs bosons in the context of the minimal supersymmetric standard model (MSSM). The data are found to be consistent with expectation from background processes. Upper limits on MSSM Higgs boson production are set for Higgs boson masses ranging from 90 to 300 GeV. We exclude tanBeta>20-30 for Higgs boson masses below 180 GeV. These are the most stringent constraints on MSSM Higgs boson production in p-pbar collisions.Comment: Submitted to Phys. Lett.

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

Test beam performance measurements for the Phase I upgrade of the CMS pixel detector

A new pixel detector for the CMS experiment was built in order to cope with the instantaneous luminosities anticipated for the Phase I Upgrade of the LHC. The new CMS pixel detector provides four-hit tracking with a reduced material budget as well as new cooling and powering schemes. A new front-end readout chip mitigates buffering and bandwidth limitations, and allows operation at low comparator thresholds. In this paper, comprehensive test beam studies are presented, which have been conducted to verify the design and to quantify the performance of the new detector assemblies in terms of tracking efficiency and spatial resolution. Under optimal conditions, the tracking efficiency is (99.95 ± 0.05) %, while the intrinsic spatial resolutions are (4.80 ± 0.25) μm and (7.99 ± 0.21) μm along the 100 μm and 150 μm pixel pitch, respectively. The findings are compared to a detailed Monte Carlo simulation of the pixel detector and good agreement is found.Peer reviewe

Measurement of the ratio of the ppˉ→Wp\bar{p}\to W+cc-jet cross section to the inclusive ppˉ→Wp\bar{p}\to W+jets cross section

We present a measurement of the fraction of inclusive $W$+jets events produced with net charm quantum number $\pm1$, denoted $W$+$c$-jet, in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using approximately 1~fb$^{-1}$ of data collected by the D0 detector at the Fermilab Tevatron Collider. We identify the $W$+jets events via the leptonic $W$ boson decays. Candidate $W$+$c$-jet events are selected by requiring a jet containing a muon in association with a reconstructed $W$ boson and exploiting the charge correlation between this muon and $W$ boson decay lepton to perform a nearly model-independent background subtraction. We measure the fraction of $W$+$c$-jet events in the inclusive $W$+jets sample for jet $p_{T}>20$ GeV and pseudorapidity $|\eta|<2.5$ to be 0.074$\pm0.019$(stat.)$\pm^{0.012}_{0.014}$(syst.), in agreement with theoretical predictions. The probability that background fluctuations could produce the observed fraction of $W$+$c$-jet events is estimated to be $2.5\times 10^{-4}$, which corresponds to a 3.5 $\sigma$ statistical significance.Comment: submitted to Physics Letters