Hernia repair with polypropylene mesh is not associated with an increased risk of autoimmune disease in adult men

Purpose

Synthetic mesh for herniorrhaphy has been placed under critical observation regarding the potential association of mesh placement and the subsequent development of autoimmune diseases. We sought to evaluate whether there is a link between synthetic polypropylene mesh repairs and the subsequent development of systemic/autoimmune disorders (SAID).

Study design

Adult men undergoing hernia repair with mesh between January 2008 and December 2009 in New York State were identified using International Classification of Diseases, Ninth Revision, Modification procedure codes and Current Procedural Terminology Coding System, Fourth Edition codes. A control cohort of men undergoing colonoscopy was created with whom to compare outcomes.

Results

A total of 29,712 patients underwent hernia repair between January 2008 and December 2009. In the control cohort, 79,265 patients underwent colonoscopy. During the entire follow-up, 475 patients undergoing hernia repair and 1305 patients in the control cohort were diagnosed with autoimmune disease. When patients were matched based on demographics, comorbidities and procedure date, hernia repair was not associated with an increased risk of developing autoimmune disease over the entire follow-up time period. 1.6% of those in the hernia group vs. 1.7% of those in the colonoscopy group developed SAID [risk ratio (95% CI): hernia vs. colonoscopy 0.93(0.79–1.09)]. No association between mesh surgery and increased risks of SAID was found at any of the specified time points (6 months, 1 year, and 2-year follow-up).

Conclusions

Mesh-based hernia repair was not associated with the development of autoimmune diseases compared to those undergoing routine screening colonoscopy.

     

The genomic binding sites of a noncoding RNA

Long noncoding RNAs (lncRNAs) have important regulatory roles and can function at the level of chromatin. To determine where lncRNAs bind to chromatin, we developed capture hybridization analysis of RNA targets (CHART), a hybridization-based technique that specifically enriches endogenous RNAs along with their targets from reversibly cross-linked chromatin extracts. CHART was used to enrich the DNA and protein targets of endogenous lncRNAs from flies and humans. This analysis was extended to genome-wide mapping of roX2, a well-studied ncRNA involved in dosage compensation in Drosophila. CHART revealed that roX2 binds at specific genomic sites that coincide with the binding sites of proteins from the male-specific lethal complex that affects dosage compensation. These results reveal the genomic targets of roX2 and demonstrate how CHART can be used to study RNAs in a manner analogous to chromatin immunoprecipitation for proteins.     

EUS-guided implantation of radiopaque marker into mediastinal and celiac lymph nodes is safe and effective

BACKGROUND: EUS is the preferred modality for local staging of esophageal cancer. The presence of a long-lasting fluoroscopically visible marker of malignant lymph nodes would facilitate subsequent radiation and surgical therapy. OBJECTIVE: To assess the feasibility of EUS-guided implantation of a radiopaque marker (tantalum) into mediastinal and celiac lymph nodes in a porcine model. SETTING: Survival experiments on six 50-kg pigs. DESIGN AND INTERVENTIONS: A linear-array echoendoscope was advanced into the esophagus and the stomach. Mediastinal and celiac lymph nodes were identified and injected with 1 mL tantalum suspension by using 19- and 22-gauge FNA needles under fluoroscopy. The pigs were recovered. Fluoroscopy was repeated after 1, 2, and 4 weeks, then a postmortem examination was performed. MAIN OUTCOME MEASUREMENTS: Long-term opacification of lymph nodes. RESULTS: It was not possible to inject tantalum through the 22-gauge FNA needle because of its rapid precipitation inside the needle, which caused needle occlusion. Intranodal injection with the 19-gauge FNA needle was easily accomplished and resulted in excellent fluoroscopic opacification of injected lymph nodes. Repeat fluoroscopy at 1, 2, and 4 weeks demonstrated stable tantalum deposition at the injection site. There were no complications. Histologic examination of harvested lymph nodes revealed intranodal tantalum depositions without signs of infection, inflammation, tissue damage, or necrosis. CONCLUSIONS: EUS-guided implantation of tantalum as a radiopaque marker into mediastinal and celiac lymph nodes in a porcine model is technically feasible, safe, and results in long-lasting intranodal depositions to facilitate subsequent surgical and radiotherapeutic interventions.     

The evidence on the effectiveness of management for malignant pleural effusion: a systematic review.

The aim of this study was to review systematically the available evidence on pleurodesis for malignant effusion, focusing on the choice of the agents, route of delivery and other strategies to improve outcomes. Four electronic databases (MEDLINE, EMBASE, Web of Science and Cochrane Controlled Trials Register) were searched, reference lists checked and letters requesting details of unpublished trials and data sent to authors of previous trials. Studies of malignant pleural effusion in humans were selected with no language restrictions applied. Criteria for randomised clinical trial (RCT) eligibility were random allocation of patients and non-concurrent use of another experimental medication or device. Methodological quality evaluation of the trials was based on randomisation, blinding, allocation concealment and intention to treat analysis. A random effect model was used to combine the relative risk estimates of the treatment effects whenever pooling for an overall effect was considered appropriate. Forty-six RCTs with a total of 2053 patients with malignant pleural effusions were reviewed for effectiveness of pleurodesis. Talc tended to be associated with fewer recurrences when compared to bleomycin (RR, 0.64; 95% CI, 0.34-1.20) and, with more uncertainty, to tetracycline (RR, 0.50; 95% CI, 0.06-4.42). Tetracycline (or doxycycline) was not superior to bleomycin (RR, 0.92; 95% CI, 0.61-1.38). When compared with bedside talc slurry, thoracoscopic talc insufflation was associated with a reduction in recurrence (RR, 0.21; 95% CI, 0.05-0.93). Strategies such as rolling the patient after instillation of the sclerosing agent, protracted drainage of the effusion and use of larger chest tubes were not found to have any substantial advantages. Talc appears to be effective and should be the agent of choice for pleurodesis. Thoracoscopic talc insufflation is associated with fewer recurrences of effusions compared with bedside talc slurry, but this is based on two small studies. Where thoracoscopy is unavailable bedside talc pleurodesis has a high success rate and is the next best option.     

Stem Cells as a Therapeutic Approach to Chronic Kidney Diseases

Much attention recently has been focused on stem cell technology as a possible alternative modality of treatment of a variety of diseases. Chronic kidney disease is a serious health problem and most chronic kidney diseases share in common the presence of interstitial and glomerular fibrosis, regardless of the underlying cause. To date there are no specific therapies aimed at treating fibrosis in the kidney. In a novel effort to address the underlying pathology in kidney disease, researchers are demonstrating that stem cell therapy can attenuate fibrosis in chronic kidney disease in animal models. This review will focus on the recent developments in stem cell research and their possible implications to treat chronic kidney disease.     

Streamlined discovery of cross-linked chromatin complexes and associated histone modifications by mass spectrometry

Posttranslational modifications (PTMs) are key contributors to chromatin function. The ability to comprehensively link specific histone PTMs with specific chromatin factors would be an important advance in understanding the functions and genomic targeting mechanisms of those factors. We recently introduced a cross-linked affinity technique, BioTAP-XL, to identify chromatin-bound protein interactions that can be difficult to capture with native affinity techniques. However, BioTAP-XL was not strictly compatible with similarly comprehensive analyses of associated histone PTMs. Here we advance BioTAP-XL by demonstrating the ability to quantify histone PTMs linked to specific chromatin factors in parallel with the ability to identify nonhistone binding partners. Furthermore we demonstrate that the initially published quantity of starting material can be scaled down orders of magnitude without loss in proteomic sensitivity. We also integrate hydrophilic interaction chromatography to mitigate detergent carryover and improve liquid chromatography-mass spectrometric performance. In summary, we greatly extend the practicality of BioTAP-XL to enable comprehensive identification of protein complexes and their local chromatin environment.Chromatin encompasses the subset of proteins and RNAs in complex with DNA to form the chromosomes within eukaryotic nuclei. As the primary protein constituents of chromatin, histones organize genomic DNA into nucleosomes and display an extensive array of posttranslational modifications (PTMs) (1). It is increasingly evident that specific histone PTMs are selectively recognized by specific nonhistone proteins that are themselves regulators of many nuclear events such as epigenetic silencing (2, 3). Consequently, defects in these chromatin components often manifest in a number of human diseases (4).As specific interactions between modified histones and nonhistone proteins help distinguish complexes participating in distinct processes, the identification of protein and modification-dependent interactions provides key insights into chromatin biology. Various chromatography and pulldown methods have been developed to identify binding partners. In a typical native pulldown experiment, nuclei from hypotonically lysed cells are digested with micrococcal nuclease (MNase). Extracted chromatin is subjected to immunoprecipitation to isolate the desired complexes. If using a tag such as FLAG, complexes are then competitively eluted and identified. Several drawbacks to native pulldowns as described here are that MNase leaves behind a substantial insoluble nuclear pellet and degrades associating RNAs, that salt extraction of the digested nucleosomes risks dissociation of the tagged bait from its interacting partners, and that most tags do not have sufficient affinity for their respective antibody to permit highly stringent washes. The result is often an incomplete picture of the chromatin-bound complex. BioTAP-XL is a technique that complements native pulldowns. BioTAP-XL uses formaldehyde to inactivate endogenous enzymes and to cross-link labile interactions with the bait, sonication to solubilize the genomic chromatin content, and high affinity tags to capture the bait and its associated factors (K_d = 10⁻⁹ and 10⁻¹⁵ M for the bipartite BioTAP tag compared with 10⁻⁸ M for the FLAG tag). Thus, BioTAP-XL captures interactions that may be inaccessible or disrupted using native pulldowns.BioTAP-XL has successfully identified key interactors of the male-specific lethal (MSL) dosage compensation and heterochromatin protein (HP1a) complexes in Drosophila (5) and revealed novel components of the Polycomb Repressive Complex 2 in human tissue culture cells (6) and fruit flies (7). Despite the aforementioned advantages, BioTAP-XL suffers from several limitations. First, the cell number requirement far exceeds the amounts typically used in standard affinity experiments, namely with 10⁸ cells for native pulldowns (8) compared with 10¹⁰ cells for BioTAP pulldown (9). Second, the high detergent concentrations used during the procedure risks interfering with liquid chromatography mass spectrometry (LC-MS). Third, our analysis of the associated histone PTMs is complicated by both the nearly irreversible binding of the tagged complexes to streptavidin and the inability to obtain histone peptides of comparable ionization efficiencies across modified states using trypsin alone.We sought to address these limitations using Drosophila and human cells expressing BioTAP-tagged factors. To demonstrate scalability, we performed parallel tandem affinity pulldowns of the same bait across various initial chromatin amounts. We recovered the core interactors of MSL3 at even the lowest tested amount of Drosophila cells. To improve detergent removal, we compared a sample processed either with conventional spin columns or hydrophilic interaction chromatography (HILIC). We observed significant improvement in LC-MS quality of the MSL3 elutions prepared using HILIC over spin columns. To facilitate histone modification analysis, we derivatized the associated histones directly on the streptavidin beads. We successfully quantified histone modifications enriched with MSL3 and HP1a from Drosophila cells and with chromobox homolog 4 (CBX4) and bromodomain-containing protein 4 (BRD4) from human cells. In short, this report streamlines BioTAP-XL for biochemically characterizing chromatin complexes and their associated histone modifications.     

Availability and Characteristics of Nonbeverage Alcohols Sold in 17 Russian Cities in 2007

Background: It is known that a range of nonbeverage alcohols including eau‐de‐colognes and medicinal tinctures are consumed by sections of the Russian population. Research conducted in a city in the Urals (2003 to 2005) showed that consumption of such products is associated with very high mortality from a wide range of causes. However, there have been no systematic attempts to investigate the extent to which such products are available in other cities of the Russian Federation. There is particular interest in establishing this following the introduction of new federal regulations in January 2006 aimed at restricting the availability of these products. Methods: In the first half of 2007, we conducted a survey in 17 cities that spanned the full range of city types in the Russian Federation excluding those in the Far East. In each city, fieldworkers visited pharmacies and other types of retail outlets and purchased samples of nonbeverage alcohols. These were defined as being typically 10 to 15 roubles per bottle, with an ethanol concentration of at least 60% by volume. Results: We were able to purchase samples of nonbeverage alcohols in each of the 17 cities we investigated. The majority of the 271 products included were a cheaper and more affordable source of ethanol than standard Russian vodka. Medicinal tinctures, sold almost exclusively in pharmacies, were particularly common with an average concentration of 78% ethanol by volume. Most importantly, the majority of the products were of a sort that our previous research in 2004 to 2005 had established were drunk by working‐age men. Conclusions: While the 2006 federal regulations introduced in part to reduce the availability and consumption of nonbeverage alcohols may have had some effect on certain classes of nonmedicinal products, up until June 2007 at least, medicinal tinctures as well as some other nonbeverage alcohols that are consumed appear to have been readily available.     

A comparison of reintervention rates after endovascular aneurysm repair between the Vascular Quality Initiative registry,Medicare claims,and chart review

Objective

The accurate measurement of reintervention after endovascular aneurysm repair (EVAR) is critical during postoperative surveillance. The purpose of this study was to compare reintervention rates after EVAR from three different data sources: the Vascular Quality Initiative (VQI) alone, VQI linked to Medicare claims (VQI-Medicare), and a “gold standard” of clinical chart review supplemented with telephone interviews.

Impact of weekend treatment on short-term and long-term survival after urgent repair of ruptured aortic aneurysms in Germany

Objective

There is some evidence that weekend admission to the hospital is associated with worse outcomes compared with weekday admission. However, only a few studies have focused on weekend vs weekday surgery outcomes. This study aimed to determine whether there is a weekend effect on outcomes in the treatment of ruptured aortic aneurysms in Germany.