Maximizing mesh mileage: evaluating the long-term performance of a novel hybrid mesh for ventral hernia repair.

PURPOSE: The objective of this study is to evaluate the safety and long-term outcomes of GORE Synecor™ in ventral hernia repair (VHR). METHODS: This retrospective, single-center case review analyzed outcomes in patients who underwent VHR with Synecor from May 2016 to December 2022. Primary outcomes were hernia recurrence and mesh infection rates. Secondary outcomes were 30-day morbidity, 30-day mortality, 30-day readmission, re-operation, surgical-site infection (SSI) and occurrence (SSO) rates, and occurrences requiring intervention (SSOI). RESULTS: 278 patients were identified. Mean follow-up was 24.1 (0.2-87.1) months. Mean hernia defect size was 63.4 (± 77.2) cm2. Overall hernia recurrence and mesh infection rates were 5.0% and 1.4% respectively. No mesh infections required full explantation. We report the following overall rates: 13.3% 30-day morbidity, 4.7% 30-day readmission, 2.9% re-operation, 7.2% SSI, 6.1% SSO, and 2.9% SSOI. 30-day morbidity was significantly higher in non-clean (42.1% vs 11.2%, p < 0.01), onlay (OL) mesh (37.0% vs preperitoneal (PP) 16.4%, p = 0.05 vs retrorectus (RR) 15.0%, p < 0.05 vs intraperitoneal (IP) 5.2%, p < 0.001), and open cases (23.5% vs 3.1% laparoscopic vs 4.4% robotic, p < 0.01). SSI rates were significantly higher in non-clean (31.6% vs 5.4%, p < 0.001), OL mesh (29.6% vs RR 11.3%, p < 0.05 vs PP 5.5%, p < 0.01 vs IP 0.0%, p < 0.001), and open cases (15.2% vs 0% laparoscopic vs 0% robotic, p < 0.05). CONCLUSION: Long-term performance of a novel hybrid mesh in VHR demonstrates a low recurrence rate and favorable safety profile in various defect sizes and mesh placement locations.

Severity of GERD and disease progression.

BACKGROUND: Many factors may play a role in the severity and progression of gastroesophageal reflux disease (GERD) since pathophysiology is multifactorial. Data regarding the progression of GERD are controversial: some reports of increased esophageal acid exposure (EAE) and mucosal damage were considered as evidence for a stable disease course, while others interprete these findings as disease progression. The aim of this study is to analyze a large patient-population with persisting symptoms indicative of GERD under protonpumpinhibitor-therapy and identify components characterizing disease severity and progression. METHODS: Patients with symptoms indicative of GERD were included in the study in a tertiary referral center (Frankfurt, Germany). All selected patients were under long-term protonpumpinhibitor-therapy with persistant symptoms. All patients underwent investigations to collect data on their physical status, EAE, severity of esophagitis, anatomical changes, and esophageal functional defects as well as their relation to the duration of the disease. Incidence over time was plotted as survival curves and tested with Log-rank tests for the four main disease markers. Multivariate modeling with COX-regression model was used to estimate the general impact of the four main disease markers on the time course of the disease. In order to elucidate possible causal relationships over time, a path analysis (structural equation model) was calculated. RESULTS: From the database with 1480 data sets, 972 patients were evaluated (542 males, 430 females). The mean age was 50.5 years (range18-89). The mean body mass index was 27.2(19-48). The mean time between the onset of symptoms and the diagnostic investigations was 8.2 years (1-50). A longer disease history for GERD was significantly associated with a higher risk for LES-incompetence. The mean duration from symptom onset to the time of clinical investigation was 9 years for patients with LES-incompetence (n = 563), compared to a mean of 6 years for those with mechanically intact LES (n = 95). A longer period from symptom onset to diagnostics was significantly associated with higher acid exposure. The pathway analysis was significant for the following model: 'history' (P < 0.001➔LES-incompetence & Hiatal Hernia➔(p < 0,001)➔pH-score (P < 0.001).Conclusion: LES-incompetence, the functional deterioration of the LES, and the anatomical alteration at the esophagogastric junction (Hiatal Hernia) as well as an increased EAE were associated with a long history of suffering from GERD. Path modeling suggests a causal sequence overtime of the main disease-parameters, tentatively allowing for a prediction of the course of the disease.

Simple preoperative risk scale accurately predicts perioperative mortality following esophagectomy for malignancy.

Surgery remains one of the major treatment options available to patients with esophageal cancer, with high mortality in certain cohorts. The aim of this study was to develop a simple preoperative risk scale based on patient factors, hospital factors, and tumor pathology to predict the risk of perioperative mortality following esophagectomy for malignancy. The Nationwide Inpatient Sample database was used to create the risk scale. Patients who underwent open or laparoscopic transhiatal and transthoracic esophageal resection were identified using International Classification of Diseases, 9th edition codes. Patients <18 years and those with peritoneal disease were excluded. Multivariate logistic regressions were used to define a predictive model of perioperative mortality and to create a simple risk scale. From 1998 to 2011, a total of 23 751 patients underwent esophagectomy. The observed overall perioperative mortality rate for this cohort was 7.7%. Minimally invasive techniques, and operations performed in higher volume centers were protective, whereas increasing age, comorbidities and diagnosis of squamous cell carcinoma were independent predictors of mortality. Based on this population, a risk scale from 0-16 was created. The calibration revealed a good agreement between the observed and risk scale-predicted probabilities. A set of sensitivity/specificity analyses was then performed to define normal (score 0-7) and high risk (score 8-16) patients for clinical practice. Mortality in patients with a score of 0-7 ranged from 1.3-7.6%, compared with 10.5-34.5% in patients with a score of 8-16. This simple preoperative risk scale may accurately predict the risk of perioperative mortality following esophagectomy for malignancy and can be used as a clinical tool for preoperative counseling.

Alcohol metabolism is not affected by sleeve gastrectomy.

INTRODUCTION: It has been published that patients who underwent gastric bypass surgery have impaired alcohol metabolism, predisposing them to higher rates of intoxication and DUI arrests. Yet the impact of laparoscopic sleeve gastrectomy (LSG) on alcohol metabolism and in particular the long-term effects are still unclear. We hypothesized that LSG does not alter alcohol metabolism. METHODS: A prospective cohort study of patients undergoing LSG was evaluated. Blood alcohol concentration (BAC) was extrapolated using a Breathalyzer(®). Alcohol metabolism was evaluated by determining BAC every 5 min after a single dose of alcohol (5 oz. glass of 14% v/v Malbec wine), until BAC was equal to zero. Subjects were queried about alcohol intoxication symptoms. All parameters were obtained and analyzed preoperatively and at 3 and 12 months postoperatively. RESULTS: Our study consisted of 10 patients (9 female) with a mean age of 46.6 ± 2.2 years and BMI of 43.5 ± 2.2 kg/m(2). The mean percentage excess weight loss was 39.5 ± 3.3 at 3 months and 55.6 ± 4.4 at 12 months. Peak BAC at 20 min was not different at 3 months (0.068 ± 0.007, p = 0.77) or at 12 months (0.047 ± 0.008, p = 0.19) when compared to the preoperative assessment (0.059 ± 0.014). In addition, the time to BAC equal to zero was not significantly different between baseline and the follow-up values (preoperative: 70 ± 9 min, 3 months: 95 ± 18 min, and 12 months: 57 ± 8 min, (p > 0.05). Symptoms of intoxication were not significantly different in patients before and after surgery. CONCLUSIONS: Our study suggests that LSG does not alter alcohol metabolism. Patients who undergo LSG do not have higher levels of intoxication following alcohol consumption and are therefore not prone to higher rates of DUI charges than the general public, in contrast to that previously reported following in patients who undergo gastric bypass surgery.

Purification and characterization of the aromatic desulfinase, 2-(2'-hydroxyphenyl)benzenesulfinate desulfinase.

2-(2(')-Hydroxyphenyl)benzenesulfinate desulfinase (HPBS desulfinase) catalyzes the cleavage of the carbon-sulfur bond of 2-(2(')-hydroxyphenyl)benzenesulfinate (HPBS) to form hydroxybiphenyl and sulfite. This is the final step in the desulfurization of dibenzothiophene, the organosulfur compound used to study biodesulfurization of petroleum middle distillate. HPBS desulfinase was purified 1600-fold from Rhodococcus IGTS8. The purification was monitored using a spectrofluorimetric assay and SDS-PAGE. The pI of HPBS desulfinase is 5.6, the temperature optimum is 35 degrees C, and the pH optimum is 7.0. HPBS desulfinase has a K(m) of 0.90+/-0.15 microM and a k(cat) of 1.3+/-0.07 min(-1). Several analogs were tested for their ability to act as substrates or inhibitors of HPBS desulfinase. No alternative substrates and very few inhibitors were identified. HPBS desulfinase activity decreases in the presence of Cu(2+) and Zn(2+), while no metals significantly enhance enzyme activity. HPBS desulfinase is susceptible to tyrosine, tryptophan, and cysteine specific modification agents.

Induction of cytotoxic T-cell responses against immunoglobulin V region-derived peptides modified at human leukocyte antigen-A2 binding residues.

Cytotoxic T-lymphocyte (CTL) responses can be generated against peptides derived from the immunoglobulin (Ig) V region in some but not all patients. The main reason for this appears to be the low peptide-binding affinity of Ig-derived peptides to major histocompatibility complex (MHC) class I molecules and their resulting low immunogenicity. This might be improved by conservative amino acid modifications at the MHC-binding residues of the peptides (heteroclitic peptides). In this study, it was found that in 18 Ig-derived peptides, that heteroclitic peptides from the Ig gene with improved binding to human leukocyte antigen (HLA)-A*0201 can be used to improve CTL responses. Amino acid substitution substantially increased predicted binding affinity, and there was a strong correlation between predicted and actual binding to HLA-A*0201. CTLs generated against the heteroclitic peptide had not only enhanced cytotoxicity against the heteroclitic peptide but also increased killing of antigen-presenting cells pulsed with the native peptide. Surprisingly, no difference was observed in the frequency of T cells detected by MHC class I peptide tetramers after stimulation with the heteroclitic peptide compared with the native peptide. CTLs generated against heteroclitic peptides could kill patients' tumor cells, showing that Ig-derived peptides can be presented by the tumor cell and that the failure to mount an immune response (among other reasons) likely results from the low immunogenicity of the native Ig-derived peptide. These results suggest that heteroclitic Ig-derived peptides can enhance immunogenicity, thereby eliciting immune responses, and that they might be useful tools for enhancing immunotherapy approaches to treating B-cell malignant diseases.

The angiogenic factor interleukin 8 is induced in non-small cell lung cancer/pulmonary fibroblast cocultures.

The interactions between tumor cells and surrounding stromal elements may promote the release of angiogenic factors. Although interleukin 8 (IL-8) is a major angiogenic factor in non-small cell lung cancer (NSCLC), the stromal contribution to IL-8 expression in primary NSCLC remains to be defined. To elucidate the role of stromal elements in NSCLC IL-8 production, normal pulmonary fibroblasts were cocultured with six representative NSCLC lines in direct and transwell assays. IL-8 transcripts and protein were consistently induced in fibroblasts and a subset of NSCLCs as a consequence of tumor/stromal coculture. In these cocultures, IL-8 was induced by IL-1alpha and an additional, as yet unidentified, soluble factor. These data underscore the importance of tumor/stromal interaction in the production of angiogenic peptides such as IL-8 in NSCLC.

Chromium(VI) inhibits the transcriptional activity of nuclear factor-kappaB by decreasing the interaction of p65 with cAMP-responsive element-binding protein-binding protein.

Chromium(VI) regulation of gene expression has been attributed to the generation of reactive chromium and oxygen species, DNA damage, and alterations in mRNA stability. However, the effects of Cr(VI) on signal transduction leading to gene expression are not resolved. Therefore, this study investigated the effects of Cr(VI) on basal and tumor necrosis factor-alpha (TNF-alpha)-induced transcriptional competence of nuclear factor-kappaB (NF-kappaB) in A549 human lung carcinoma cells. Pretreatment of A549 cells with nontoxic levels of Cr(VI) inhibited TNF-alpha-stimulated expression of the endogenous gene for interleukin-8 and of an NF-kappaB-driven luciferase gene construct, but not expression of urokinase, a gene with a more complex promoter. Chromium did not inhibit TNF-alpha-stimulated IkappaBalpha degradation or translocation of NF-kappaB-binding proteins to the nucleus. However, Cr(VI) pretreatments prevented TNF-alpha-stimulated interactions between the p65 subunit of NF-kappaB and the transcriptional cofactor cAMP-responsive element-binding protein-binding protein (CBP). This inhibition was not the result of an effect of chromium on the protein kinase A catalytic activity required for p65/CBP interactions. In contrast, Cr(VI) caused concentration-dependent increases in c-Jun/CBP interactions. These data indicate that nontoxic levels of hexavalent chromium selectively inhibit NF-kappaB transcriptional competence by inhibiting interactions with coactivators of transcription rather than DNA binding.

The presence of 4-hydroxynonenal/protein complex as an indicator of oxidative stress after experimental spinal cord contusion in a rat model.

OBJECT: The authors tested the hypothesis that breach of the blood-spinal cord barrier (BSCB) will produce evidence of oxidative stress and that a similar staining pattern will be seen between 4-hydroxynonenal (HNE)/protein complexes and extravasated immunoglobulin G (IgG). METHODS: Adult female Fischer 344 rats, each weighing 200 to 225 g, were subjected to a spinal cord contusion at T-10 by means of a weight-drop device. Spinal cord tissue was assessed for oxidative stress by localizing extravasated plasma contents with a monoclonal antibody for rat IgG and protein conjugation with HNE, which is an aldehyde byproduct of lipid peroxidation. The animals were killed at 1 and 6 hours, and 1, 2, and 7 days after surgery. Maximum HNE/protein staining was observed at 2 days postinjury, and HNE/protein and IgG manifested similar staining patterns. Analysis revealed a graduated but asymmetrical rostral-caudal response relative to the T-10 injury site. Both HNE/protein complex and IgG staining revealed that the caudal levels T-11 and T-12 stained significantly more intensely than the rostral levels T-9 and T-8, respectively. A higher percentage of neurons positive for HNE/protein immunostaining was observed in spinal cord levels caudal to the injury site compared with equidistant rostral regions. Protein dot-blot assays also revealed a similar asymmetrical rostral-caudal HNE/protein content. To analyze the timing of the BSCB breach, another group of animals received identical contusions, and horseradish peroxidase (HRP) was injected 10 minutes before or at various times after injury (1, 3, and 6 hours, and 1, 2, and 7 days). Maximum HRP permeability was seen immediately after injury, with a significant decrease occurring by 1 hour and a return to control levels by 2 days posttrauma. CONCLUSIONS: Data from this study indicate possible compromise of neuronal, axonal, glial, and synaptic function after trauma, which may be a factor in motor deficits seen in animals after spinal cord contusion. The colocalization of the IgG stain with the HNE/protein stain is consistent with the hypothesis of a mutual cause-effect relationship between BSCB and oxidative stress in central nervous system trauma.

Alterations in temporal/spatial distribution of GFAP- and vimentin-positive astrocytes after spinal cord contusion with the New York University spinal cord injury device.

Astrocytes become reactive as a result of various types of lesions and upregulate 2 intermediate filaments, glial fibrillary acidic protein (GFAP), and the developmentally regulated protein vimentin. Young female Sprague-Dawley rats were subjected to a spinal cord contusion at segment T10 using the New York University injury device. Animals were killed at 1, 2, 7, 14, and 30 days postinjury. Horizontal spinal cord sections spanning segments T7-T13 were assessed with antibodies to both intermediate filament proteins. The number of gray matter GFAP-positive astrocytes increased by 2 days postinjury, with segments adjacent (proximal) to the injury site showing greater responses than areas several segments away (distal). By 30 days following injury, astroglial cell numbers returned to normal levels. Vimentin-positive astrocytes also showed a graded proximal/distal response by 2 days following injury. Proximal regions remained significantly higher at 30 days following injury than control animals. Rostral/caudal changes were also evident, with regions caudal to the injury showing significantly higher numbers of vimentin positive astrocytes than those rostral, indicating that gray matter areas caudal to spinal cord injury may undergo more stress following spinal cord injury.

Fusiform P1 segment artery aneurysm in a pediatric patient: technical case report.

We present an unusual aneurysm in a pediatric patient. Due to the fusiform nature of the aneurysm and the small size of the patient, a unique surgical solution was applied. One year of clinical follow-up is also provided.

Intracellular internalization and signaling pathways triggered by the large subunit of HSV-2 ribonucleotide reductase (ICP10).

The large subunit of the HSV-2 ribonucleotide reductase (RR) (ICP10) is a chimera consisting of a serine threonine (Ser/Thr) protein kinase domain at the amino terminus and the RR domain at the carboxy terminus. Transformed human cells that constitutively express ICP10 (JHLa1) were stained with anti-LA-1 antibody (recognizes ICP10 amino acids 13-26) and immunogold-conjugated goat anti-rabbit IgG and were examined by electron microscopy. ICP10-associated gold particles were observed on the cell surface and in structures with ultrastructural characteristics of endocytic vesicles, multivesicular bodies, and lysosomes, consistent with endocytic internalization. ICP10 was also associated with the cytoskeleton fraction of JHLa1 cells and, at least in part, it colocalized with actin filaments. This was evidenced by immunoprecipitation of [35S]methionine-labeled cell fractions and immunofluorescent staining of Triton-treated cells with anti-LA-1 antibody and phalloidin. Endocytic localization of gold particles was not seen in cells that constitutively express the ICP10 transmembrane (TM)-deleted mutant p139TM (JHL15). p139TM did not associate with the cytoskeleton and was almost entirely localized within the cytoplasm. raf and Erk evidenced decreased mobility consistent with an activated state in JHLa1, but not JHL15, cells, and chloramphenicol acetyl transferase (CAT) expression from a c-fos/cat hybrid construct was significantly increased in JHLa1 but not JHL15 cells. The data indicate that effector molecules downstream of ras are activated in JHLa1 cells and the ICP10 TM segment plays a critical role in ICP10 intracellular localization and its ability to activate signaling pathways. This behavior is analogous to that of an activated growth factor receptor kinase.

Determination of the mechanism of free radical generation in human aortic endothelial cells exposed to anoxia and reoxygenation.

Endothelial cell-derived oxygen free radicals are important mediators of postischemic injury; however, the mechanisms that trigger this radical generation are not known, and it is not known if this process can occur in human cells and tissues. The enzyme xanthine oxidase can be an important source of radical generation; however, it has been reported that this enzyme may not be present in human endothelium. To determine the presence and mechanisms of radical generation in human vascular endothelial cells subjected to anoxia and reoxygenation, electron paramagnetic resonance measurements were performed on cultured human aortic endothelial cells using the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). These measurements were correlated with cellular injury, xanthine oxidase activity, and alterations in cellular nucleotides. Upon reoxygenation after 60 min of anoxia, large DMPO-OH (aN = aH = 14.9 G) and smaller DMPO-R (aN = 15.8 G, aH = 22.8 G) signals were seen. Superoxide dismutase totally quenched this radical generation. The ferric iron chelator deferoxamine prevented cell death and totally quenched the DMPO-R signal with a 40% decrease in the DMPO-OH signal. Xanthine oxidase was shown to be present in these cells and to be the primary source of free radicals. While the concentration of this enzyme did not change after anoxia, the concentration of its substrate, hypoxanthine, markedly increased, resulting in increased free radical generation upon reoxygenation. Thus, reoxygenated human vascular endothelial cells generate superoxide free radicals, which further react with iron to form the reactive hydroxyl radical, which in turn causes cell death. Xanthine oxidase was the primary source of radical generation with this process triggered by the breakdown of ATP to the substrate hypoxanthine during anoxia.

A field methodology for the control of musculoskeletal injuries.

A methodology is presented for the evaluation of jobs prone to cumulative trauma disorders (CTDs) and manual material handling (MMH) injuries, which combines various tested ergonomics methodologies into a single, coherent programme. This multi-step procedure is based upon the collection of quantitative data that are used to evaluate ergonomic changes with respect to biomechanical risk, perceived comfort, productivity and quality. A method for prioritizing changes, related to cost-benefit analysis, is proposed to guide the selection of ergonomic changes in order to maximize the potential for injury reduction under specified cost constraints. The ten-step methodology has been extensively applied in industry, leading to examples and a case study.

Cholesterol-induced changes in rabbit arterial smooth muscle sensitivity to adrenergic stimulation.

We evaluated the effects of exposure to high cholesterol levels for 3 h on arterial smooth muscle responses to adrenergic stimulation. Femoral arteries from Dutch belted rabbits were perfused in vitro with a constant-flow variable-pressure perfusion apparentus. After equilibration the vessels were perfused for 180 min more with media supplemented with cholesterol-phospholipid (C/PL) liposomes of molar ratios of 2:1 or 0.5:1. Although resting vascular resistance was unchanged, norepinephrine (NE) concentration-response analyses revealed a fivefold increase in NE sensitivity (P less than 0.001) in the arteries perfused with the cholesterol-enriched liposomes (2:1) compared with control arteries perfused with the 0.5:1 liposome medium. The arteries perfused with the cholesterol-enriched liposomes demonstrated a 60% increase in cholesterol content and a marked (90%) reduction in Na+-K+-ATPase activity. The increased sensitivity of the cholesterol-enriched arteries was not mediated by acute reductions in Na-pump activity, altered endothelial function, adrenergic nerve function, or prostaglandin production. Cholesterol-induced sensitization to NE did demonstrate an absolute dependence on extra-cellular calcium. These findings suggest that an increase in the free cholesterol content of the arterial smooth muscle cell plasma membrane alters membrane permeability to extracellular calcium during adrenergic stimulation.

Use of a community task force by hospitals to improve systems of care.

A community task force is effective in the strategic planning process for improvement of health care services in a continuum of care. This article describes the role of a community task force in developing services for senior citizens within the mission of a hospital. A case study is presented demonstrating how a hospital benefited from a task force with a focus on senior care.

Two structurally distinct calcium storage sites in rat cardiac sarcoplasmic reticulum: an electron microprobe analysis study.

The elemental composition of subcellular organelles in resting rat papillary muscle was measured by electron probe x-ray microanalysis of cryosections of flash-frozen tissue. Nonmitochondrial electron-dense structures (50-100 nm in diameter) with a phosphorous concentration larger than 375 mmol/kg dry wt were identified in the interfibrillar spaces of the I band region. They were not visible in the proximity of transverse tubules. The sodium, magnesium, phosphorus, sulfur, chlorine, and potassium content of the electron dense structures showed a normal distribution, consistent with a uniform composition of a specific subcellular organelle. However, the distribution of the calcium concentrations in these electron-dense structures was bimodal, suggesting that they are composed of at least two subpopulations. One subpopulation had relatively high calcium (up to 53 mmol/kg dry wt) content with a mean value of 12.5 +/- 1.1 mmol/kg dry wt, while the other one had a relatively low calcium content with a mean value of 2.8 +/- 0.3 mmol/kg dry wt. The mean calcium concentration in the junctional sarcoplasmic reticulum (j-SR) in rat papillary muscle with calcium concentrations larger than 6 mmol/kg dry wt was 14.6 +/- 2.0 mmol/kg dry wt. We propose that the electron-dense structures described above correspond to nonjunctional sarcoplasmic reticulum and that the population containing relatively high calcium concentrations is calsequestrin-containing corbular sarcoplasmic reticulum (c-SR) confined to the I band region, while the population containing relatively low calcium concentrations corresponds to anastomosing regions of the network sarcoplasmic reticulum that lack calsequestrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial-specific granules in situ have high calcium content, are acidic, and maintain anion gradients.

The composition and pH of atrial-specific granules of rat heart were determined by electron probe x-ray microanalysis and fluorescence microscopy, respectively. The high (75 mmol/kg of dry weight) calcium content and higher than cytoplasmic concentration of chloride in atrial-specific granules were visualized in high-resolution x-ray maps. The Cl- content of granules and cytoplasm decreased and a bromide gradient (granule greater than cytoplasm) was established during incubation in low-chloride, NaBr-containing solutions. Scanning confocal fluorescence light microscopy of live atria incubated with acridine orange demonstrated dye accumulation, indicative of low intragranular pH. We conclude that the granules represent a hitherto unrecognized intracellular store of cardiac calcium and can develop and maintain an anion gradient, presumably through cotransport by means of a proton-pumping ATPase.