SAGES research agenda in gastrointestinal and endoscopic surgery: updated results of a Delphi study

Background

Research in gastrointestinal and endoscopic surgery has witnessed unprecedented growth since the introduction of minimally invasive techniques in surgery. Coordination and focus of research efforts could further advance this rapidly expanding field. The objective of this study was to update the SAGES research agenda for gastrointestinal and endoscopic surgery.

Methods

A modified Delphi methodology was used to create the research agenda. Using an iterative, anonymous web-based survey, the general membership and leadership of SAGES were asked for input over three rounds. Initially submitted research questions were reviewed and consolidated by an expert panel and redistributed to the membership for priority ranking using a 5-point Likert scale of importance. The top 40 research questions of this round were then redistributed to and re-rated by members, and a final ranking was established. Comparisons were made between membership and leadership responses.

Results

283 initially submitted research questions were condensed into 89 distinct questions, which were rated by 388 respondents to determine the top 40 questions. 460 respondents established the final ranking of these 40 most important research questions. Topics represented included training and technique, gastrointestinal, hernia, GERD, bariatric surgery, and endoscopy. The top question was, “How do we best train, assess, and maintain proficiency of surgeons and surgical trainees in flexible endoscopy, laparoscopy, and open surgery?” 28 % of responders were leadership and the rest general members with the majority of ratings (73 %) being similar between the groups. While SAGES leadership rated the majority of questions (89 %) lower, they rated nonclinical questions higher compared with general membership.

Conclusions

An updated research agenda for gastrointestinal and endoscopic surgery was developed using a systematic methodology. This agenda may assist investigators and funding organizations to concentrate their efforts in the highest research priority areas and editors and reviewers in assessing the merit and relevance of scientific work.     

Epidemic Diffusion of OXA-23-Producing Acinetobacter baumannii Isolates in Italy: Results of the First Cross-Sectional Countrywide Survey

Carbapenem-resistant Acinetobacter baumannii (CRAb) is emerging worldwide as a public health problem in various settings. The aim of this study was to investigate the prevalence of CRAb isolates in Italy and to characterize their resistance mechanisms and genetic relatedness. A countrywide cross-sectional survey was carried out at 25 centers in mid-2011. CRAb isolates were reported from all participating centers, with overall proportions of 45.7% and 22.2% among consecutive nonreplicate clinical isolates of A. baumannii from inpatients (n = 508) and outpatients (n = 63), respectively. Most of them were resistant to multiple antibiotics, whereas all remained susceptible to colistin, with MIC₅₀ and MIC₉₀ values of ≤0.5 mg/liter. The genes coding for carbapenemase production were identified by PCR and sequencing. OXA-23 enzymes (found in all centers) were by far the most common carbapenemases (81.7%), followed by OXA-58 oxacillinases (4.5%), which were found in 7 of the 25 centers. In 6 cases, CRAb isolates carried both bla_OXA-23-like and bla_OXA-58-like genes. A repetitive extragenic palindromic (REP)-PCR technique, multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine the genetic relationships among representative isolates (n = 55). Two different clonal lineages were identified, including a dominant clone of sequence type 2 (ST2) related to the international clone II (sequence group 1 [SG1], SG4, and SG5) and a clone of ST78 (SG6) previously described in Italy. Overall, our results demonstrate that OXA-23 enzymes have become the most prevalent carbapenemases and are now endemic in Italy. In addition, molecular typing profiles showed the presence of international and national clonal lineages in Italy.     

Heart rate recovery normality data recorded in response to a maximal exercise test in physically active men

Background

Despite a growing clinical interest in determining the heart rate recovery (HRR) response to exercise, the limits of a normal HRR have not yet been well established.

Purpose

This study was designed to examine HRR following a controlled maximal exercise test in healthy, physically active adult men.

Methods

The subjects recruited (n = 789) performed a maximal stress test on a treadmill. HRR indices were calculated by subtracting the first and third minute heart rates (HRs) during recovery from the maximal HR obtained during stress testing and designated these as HRR-1 and HRR-3, respectively. The relative change in HRR was determined as the decrease in HR produced at the time points 1 and 3 min after exercise as a percentage of the peak HR (%HRR-1/HR_peak and %HRR-3/HR_peak, respectively). Percentile values of HRR-1 and HRR-3 were generated for the study population.

Results

Mean HHR-1 and HHR-3 were 15.24 ± 8.36 and 64.58 ± 12.17 bpm, respectively, and %HRR-1/HR_peak and %HRR-3/HR_peak were 8.60 ± 4.70 and 36.35 ± 6.79 %, respectively. Significant correlation was detected between Peak VO₂ and HRR-3 (r = 0.36; p < 0.001) or %HRR-3/HR_peak (r = 0.23; p < 0.001).

Conclusions

Our study provides normality data for HRR following a maximal Ergometry test obtained in a large population of physically active men.     

Levels of Aflatoxin M1 in Breast Milk of Lactating Mothers in Monterrey,Mexico: Exposure and Health Risk Assessment of Newborns

The present study aimed to determine the presence of the aflatoxin M1 (AFM1) in breast milk samples from 123 nursing women and the degree of exposure of infants to this toxin, in the metropolitan area of Monterrey, Nuevo Leon state (northeast Mexico). Upon analysis, 100% of the samples were found to be contaminated with the toxin at an average concentration of 17.04 ng/L, with a range of 5.00 to 66.23 ng/L. A total of 13.01% of the breast milk samples exceeded the regulatory limit of 25 ng/L for AFM1 concentration, set by the European Union. The estimated daily intake for AFM1 and the carcinogenic risk index were also determined in the 0- to 6-, 7- to 12-, 13- to 24-, and 25- to 36-month-old age groups. The AFM1 intake through breast milk ranged from 1.09 to 20.17 ng/kg weight/day, and was higher than the tolerable daily intake, indicating a carcinogenic risk for infants in the age groups of 0- to 24-months old. This evidence demonstrates a susceptibility of breast milk to AFM1 contamination that may suggest a carcinogenic risk for the breastfed infants in Monterrey city, Nuevo Leon state, and the need to control the presence of aflatoxins in foods eaten by nursing mothers.     

Dengue fever during pregnancy. Cases report

Dengue is known as an endemic disease of tropical and subtropical regions. It was considered a disease very frequent on kids, but recently an increase was reported on adult people. Some of these cases were related to pregnant women, for that reason, we decided to check eight cases, including just the mothers who presented dengue virus infection through ELISA IgM. IgG and ELISA IgM studies. Five products were determined between 3 and 9-born-babies. Eight cases of dengue were analyzed during pregnancy, three cases of fever dengue and five cases of hemorrhagic dengue; main complications detected were threat of abortion, and premature labour, postsurgical bleeding with desiccant haematoma of uterine artery, oligohydramnios, as well as pleural effusion, two of the neonates were classified as septic for presenting fever. In no case, IgG or IgM for fever dengue was detected in neonates.     

Esophageal atresia and tracheoesophageal fistula in two infants born to hyperthyroid women receiving methimazole (tapazol®) during pregnancy

We report on 2 newborn infants with esophageal atresia and tracheoesophageal fistula (EA + TEF) born to hyperthyroid mothers receiving methimazole (Tapazol ®) before and during their entire pregnancies. Both mothers were euthyroid during gestation and developed hydramnios diagnosed during weeks 34 and 33 of gestation. Premature delivery (36.2 weeks of gestation) occurred in one case, and both newborn infants were small for date with palpable goiter; one of them had other associated malformations. Hypo-thyroidism was diagnosed by laboratory tests in both cases. Corrective surgery was undertaken, but both newborn infants developed septicemia and renal insufficiency and died in the first week of life. The EA + TEF and a normally placed enlarged thyroid gland were confirmed at necropsy. These cases represent a previously unreported example of the association of maternal ingestion of methimazole during pregnancy and EA + TEF. © 1992 Wiley-Liss, Inc.     

Fluoride Treatment and In Vitro Corrosion Behavior of Mg-Nd-Y-Zn-Zr Alloys Type

Fluoride conversion coatings on Mg present many advantages, among which one can find the reduction of the corrosion rate under “in vivo” or “in vitro” conditions and the promotion of the calcium phosphate deposition. Moreover, the fluoride ions released from MgF₂ do not present cytotoxic effects and inhibit the biofilm formation, and thus these treated alloys are very suitable for cardiovascular stents and biodegradable orthopedic implants. In this paper, the biodegradation behavior of four new magnesium biodegradable alloys that have been developed in the laboratory conditions, before and after surface modifications by fluoride conversion (and sandblasting) coatings, are analyzed. We performed structural and surface analysis (XRD, SEM, contact angle) before and after applying different surface treatments. Furthermore, we studied the electrochemical behavior and biodegradation of all experimental samples after immersion test performed in NaCl solution. For a better evaluation, we also used LM and SEM for evaluation of the corroded samples after immersion test. The results showed an improved corrosion resistance for HF treated alloy in the NaCl solution. The chemical composition, uniformity, thickness and stability of the layers generated on the surface of the alloys significantly influence their corrosion behavior. Our study reveals that HF treatment is a beneficial way to improve the biofunctional properties required for the studied magnesium alloys to be used as biomaterials for manufacturing the orthopedic implants.     

Loss of glucose 6-phosphate dehydrogenase function increases oxidative stress and glutaminolysis in metastasizing melanoma cells

The pentose phosphate pathway is a major source of NADPH for oxidative stress resistance in cancer cells but there is limited insight into its role in metastasis, when some cancer cells experience high levels of oxidative stress. To address this, we mutated the substrate binding site of glucose 6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pentose phosphate pathway, in patient-derived melanomas. G6PD mutant melanomas had significantly decreased G6PD enzymatic activity and depletion of intermediates in the oxidative pentose phosphate pathway. Reduced G6PD function had little effect on the formation of primary subcutaneous tumors, but when these tumors spontaneously metastasized, the frequency of circulating melanoma cells in the blood and metastatic disease burden were significantly reduced. G6PD mutant melanomas exhibited increased levels of reactive oxygen species, decreased NADPH levels, and depleted glutathione as compared to control melanomas. G6PD mutant melanomas compensated for this increase in oxidative stress by increasing malic enzyme activity and glutamine consumption. This generated a new metabolic vulnerability as G6PD mutant melanomas were more dependent upon glutaminase than control melanomas, both for oxidative stress management and anaplerosis. The oxidative pentose phosphate pathway, malic enzyme, and glutaminolysis thus confer layered protection against oxidative stress during metastasis.

The pentose phosphate pathway is an important source of NADPH for oxidative stress resistance (1–5). The oxidative branch of the pentose phosphate pathway contains two enzymes that generate NADPH from NADP⁺, glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) (SI Appendix, Fig. S1). NADPH is an important source of reducing equivalents for oxidative stress resistance because it is used by cells to convert oxidized glutathione (GSSG) to glutathione (GSH), an abundant redox buffer. Complete deficiency for G6PD is embryonic-lethal in mice (2, 6, 7) but hypomorphic G6PD mutations are common in certain human populations, perhaps because they protect against malaria (8, 9). These partial loss-of-function G6PD mutations are well tolerated in adults, though they sensitize red blood cells to hemolysis from oxidative stress under certain circumstances (10).Several studies have reported a lower incidence and mortality for certain cancers in people with hypomorphic mutations in G6PD (11–14), suggesting that cancer cells depend upon G6PD to manage oxidative stress. Cells experience high levels of oxidative stress during certain phases of cancer development and progression, including during metastasis (15–17). Antioxidant mechanisms thus promote the survival of cells during oncogenic transformation (18, 19) as well as during metastasis (15, 16). For example, relative to primary cutaneous tumors, metastasizing melanoma cells exhibit increased dependence upon the folate pathway (15), monocarboxylate transporter-1 (MCT1) (20), and glutathione peroxidase-4 (GPX4) (21), each of which directly or indirectly attenuate oxidative stress. By better understanding the mechanisms that confer oxidative stress resistance in cancer cells, it may be possible to develop pro-oxidant therapies that inhibit cancer progression by exacerbating the oxidative stress experienced by cancer cells.G6PD (22) or PGD deficiency (23–25) reduce the growth of some cancers, including melanoma, but G6PD deficiency has little effect on primary tumor formation by K-Ras–driven epithelial cancers (26). This is at least partly because loss of G6PD in these cancers leads to compensatory increases in the function of other NADPH-generating enzymes, including malic enzyme and isocitrate dehydrogenase (1, 27). Nonetheless, pentose phosphate pathway function may increase during metastasis (20, 28–30) and higher G6PD expression is associated with worse outcomes in several cancers (31–33), raising the question of whether metastasizing cells are particularly dependent upon G6PD. G6PD is not essential for metastasis in a breast cancer cell line but it reduces their capacity to form metastatic tumors (26).Melanoma cells show little evidence of oxidative stress in established primary tumors but exhibit increased levels of reactive oxygen species (ROS) and dependence upon antioxidant mechanisms during metastasis (15, 20, 21). To test if these cells are more dependent upon the pentose phosphate pathway during metastasis, we generated three G6PD mutant melanomas, including two patient-derived xenografts and one human melanoma cell line. Reduced G6PD function had little effect on the formation or growth of primary subcutaneous tumors but significantly increased ROS levels and reduced spontaneous metastasis. G6PD mutant melanomas compensated by increasing malic enzyme activity and glutamine consumption, both to increase oxidative stress resistance and to replenish tricarboxylic acid (TCA) cycle intermediates through anaplerosis. Melanoma cells thus have redundant layers of protection against oxidative stress during metastasis, including the abilities to alter fuel consumption and antioxidant pathway utilization.