A primer for the student joining the general thoracic surgery service tomorrow: Primer 2 of 7.

This medical student primer discusses general thoracic surgery, which involves treating pathologies involving all structures in the thorax except the heart, thoracic aorta, great vessels, and spine

Transglutaminase inhibition ameliorates experimental diabetic nephropathy

Diabetic nephropathy is characterized by excessive extracellular matrix accumulation resulting in renal scarring and end-stage renal disease. Previous studies have suggested that transglutaminase type 2, by formation of its protein crosslink product epsilon-(gamma-glutamyl)lysine, alters extracellular matrix homeostasis, causing basement membrane thickening and expansion of the mesangium and interstitium. To determine whether transglutaminase inhibition can slow the progression of chronic experimental diabetic nephropathy over an extended treatment period, the inhibitor NTU281 was given to uninephrectomized streptozotocin-induced diabetic rats for up to 8 months. Effective transglutaminase inhibition significantly reversed the increased serum creatinine and albuminuria in the diabetic rats. These improvements were accompanied by a fivefold decrease in glomerulosclerosis and a sixfold reduction in tubulointerstitial scarring. This was associated with reductions in collagen IV accumulation by 4 months, along with reductions in collagens I and III by 8 months. This inhibition also decreased the number of myofibroblasts, suggesting that tissue transglutaminase may play a role in myofibroblast transformation. Our study suggests that transglutaminase inhibition ameliorates the progression of experimental diabetic nephropathy and can be considered for clinical application

Genetic variation in vitamin D-related genes and risk of colorectal cancer in African Americans

PurposeDisparities in both colorectal cancer (CRC) incidence and survival impact African Americans (AAs) more than other US ethnic groups. Because vitamin D is thought to protect against CRC and AAs have lower serum vitamin D levels, genetic variants that modulate the levels of active hormone in the tissues could explain some of the cancer health disparity. Consequently, we hypothesized that genetic variants in vitamin D-related genes are associated with CRC risk.MethodsTo test this hypothesis, we studied 39 potentially functional single-nucleotide polymorphisms (SNPs) in eight genes (CYP2R1, CYP3A4, CYP24A1, CYP27A1, CYP27B1, GC, DHCR7, and VDR) in 961 AA CRC cases and 838 healthy AA controls from Chicago and North Carolina. We tested whether SNPs are associated with CRC incidence using logistic regression models to calculate p values, odds ratios, and 95% confidence intervals. In the logistic regression, we used a log-additive genetic model and used age, gender, and percent West African ancestry, which we estimated with the program STRUCTURE, as covariates in the models.ResultsA nominally significant association was detected between CRC and the SNP rs12794714 in the vitamin D 25-hydroxylase gene CYP2R1 (p=0.019), a SNP that has previously been associated with serum vitamin D levels. Two SNPs, rs16847024 in the GC gene and rs6022990 in the CYP24A1 gene, were nominally associated with left-sided CRC (p=0.015 and p=0.018, respectively).ConclusionsOur results strongly suggest that genetic variation in vitamin D-related genes could affect CRC susceptibility in AAs. Electronic supplementary materialThe online version of this article (doi:10.1007/s10552-014-0361-y) contains supplementary material, which is available to authorized users

The effect of volume on esophageal cancer resections: What constitutes acceptable resection volumes for centers of excellence?

ObjectiveVolume–outcome relationships for esophageal cancer resection have been well described with centers of excellence defined by volume. No consensus exists for what constitutes a “high-volume” center. We aim to determine if an objective evidence-based threshold of operative volume associated with improvement in operative outcome for esophageal resections can be defined.MethodsRetrospective analysis was performed on patients undergoing esophageal resection for cancer in the 1998 to 2005 Nationwide Inpatient Sample. A series of multivariable analyses were performed, changing the resection volume cutoff to account for the range of annual hospital resections. The goodness of fit of each model was compared by pseudo r2, the amount of data variance explained by each model.ResultsA total of 4080 patients underwent esophageal resection. The median annual hospital resection volume was 4 (range: 1–34). The mortality rate of “high-volume” centers ranged from 9.94% (≥2 resection/year) to 1.56% (≥30 resections/year). The best model was with an annual hospital resection volume greater than or equal to 15 (3.87% of data variance explained). The difference in goodness of fit between the best model and other models with different volume cutoffs was 0.64%, suggesting that volume explains less than 1% of variance in perioperative death.ConclusionOur data do not support the use of volume cutoffs for defining centers of excellence for esophageal cancer resections. Although volume has an incremental impact on mortality, volume alone is insufficient for defining centers of excellence. Volume seems to function as an imperfect surrogate for other variables, which may better define centers of excellence. Additional work is needed to identify these variables

Effect of Pregnancy on Adverse Outcomes After General Surgery Supplemental content at jamasurgery.com Original Investigation (Reprinted) E1

IMPORTANCE The literature regarding the occurrence of adverse outcomes following nonobstetric surgery in pregnant compared with nonpregnant women has conflicting findings. Those differing conclusions may be the result of inadequate adjustment for differences between pregnant and nonpregnant women. It remains unclear whether pregnancy is a risk factor for postoperative morbidity and mortality of the woman after general surgery. RESULTS The unmatched cohorts included 2764 pregnant women (50.5% underwent emergency surgery) and 516 705 nonpregnant women (13.2% underwent emergency surgery) undergoing general surgery. After propensity matching, there were no meaningful differences in all 63 preoperative characteristics between 2539 pregnant and 2539 nonpregnant patients (all standardized differences, <0.1). The 30-day mortality rates were similar (0.4% in pregnant women vs 0.3% in nonpregnant women; P = .82), and the rate of overall morbidity was also not significantly different between pregnant vs nonpregnant patients (6.6% vs 7.4%; P = .30). CONCLUSIONS AND RELEVANCE There was no significant difference in overall morbidity or 30-day mortality rates in pregnant and nonpregnant propensity-matched women undergoing similar general surgical operations. General surgery appears to be as safe for pregnant women as it is for nonpregnant women