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Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [−18.0 to 32.4] to 57.6 [16.3–98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4–3.5] to 0 [0–1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03471611.

Background: Previous percutaneous coronary intervention risk models were focused on single outcome, such as mortality or bleeding, etc, limiting their applicability. Our objective was to develop contemporary percutaneous coronary intervention risk models that not only determine in-hospital mortality but also predict postprocedure bleeding, acute kidney injury, and stroke from a common set of variables. Methods: We built risk models using logistic regression from first percutaneous coronary intervention for any indication per patient (n=19 322, 70.6% with acute coronary syndrome) using the Mayo Clinic registry from January 1, 2000 to December 31, 2016. Approval for the current study was obtained from the Mayo Foundation Institutional Review Board. Patients with missing outcomes (n=4183) and those under 18 (n=10) were removed resulting in a sample of 15 129. We built both models that included procedural and angiographic variables (Models A) and precatheterization model (Models B). Results: Death, bleeding, acute kidney injury, and stroke occurred in 247 (1.6%), 650 (4.3%), 1184 (7.8%), and 67 (0.4%), respectively. The C statistics from the test dataset for models A were 0.92, 0.70, 0.77, and 0.71 and for models B were 0.90, 0.67, 0.76, and 0.71 for in-hospital death, bleeding, acute kidney injury, and stroke, respectively. Bootstrap analysis indicated that the models were not overfit to the available dataset. The probabilities estimated from the models matched the observed data well, as indicated by the calibration curves. The models were robust across many subgroups, including women, elderly, acute coronary syndrome, cardiogenic shock, and diabetes. Conclusions: The new risk scoring models based on precatheterization variables and models including procedural and angiographic variables accurately predict in-hospital mortality, bleeding, acute kidney injury, and stroke. The ease of its application will provide useful prognostic and therapeutic information to both patients and physicians.

Introduction:This study explored differences in testicular cancer presentation, treatment, compliance and outcomes among ethnicities in New Mexico.Methods:A retrospective review of patients...

Objective Comparative analyses of survival and funding statistics in cancers with high mortality were performed to quantify discrepancies and identify areas for intervention. Background Discrepancies in research funding may contribute to stagnant survival rates in pancreatic ductal adenocarcinoma (PDAC). Methods The Surveillance, Epidemiology, and End Results database was queried for survival statistics. Funding data were obtained from the National Cancer Institute (NCI). Clinical trial data were obtained from www.clinicaltrials.gov. Cancers with high mortality were included for analyses. Results Since 1997, PDAC has received lesser funding ($1.41 billion) than other cancers such as breast ($10.52 billion), prostate ($4.93 billion), lung ($4.80 billion), and colorectal ($4.50 billion). Similarly, fewer clinical trials have been completed in PDAC (n = 608) compared with breast (n = 1904), lung (n = 1629), colorectal (n = 1080), and prostate (n = 1055) cancer. Despite this, since 1997, dollars invested in PDAC research produced a greater return on investment with regards to 5-year overall survival (5Y-OS) compared with breast, prostate, uterine, and ovarian cancer. Incremental cost-effectiveness analysis demonstrates that millions (liver, non-Hodgkin lymphoma, and melanoma) and billions (colorectal and lung) of dollars were required for each additional 1% increase in 5Y-OS compared with PDAC. Funding of research towards early diagnosis of PDAC has decreased by 19% since 2007. For nearly all cancers, treatment-related research receives the highest percentage of NCI funding. Conclusions Funding of PDAC research is significantly less than other cancers, despite its higher mortality and greater potential to improve 5Y-OS. Increased awareness and lobbying are required to increase funding, promote research, and improve survival.

INTRODUCTION AND OBJECTIVE:Lipid accumulation in clear cell renal cell carcinoma (ccRCC) partly depends on loss of VHL and accumulation of HIF. HIF activation represses CPT1a expression, the main l...

Optimal management following index laparotomy is poorly defined in secondary peritonitis patients. Although "open abdomen" (OA), or temporary abdominal closure with planned relaparotomy, is used to reassess bowel viability or severity of contamination, recent studies demonstrate comparable morbidity and mortality with primary abdominal closure (PC). This study evaluates differences between OA and PC following emergent laparotomy.Using the Premier database at a quaternary care center (2012-2016), nontrauma patients with secondary peritonitis requiring emergent laparotomy were identified (N = 534). Propensity matching for PC (n = 331; 62%) or OA (n = 203; 38%) was performed using variables: Mannheim Peritonitis Index, lactate, and vasopressor requirement. One hundred eleven closely matched pairs (PC:OA) were compared.Five hundred thirty-four patients (55.0% female; mean age, 59.6 ± 15.5 years) underwent emergent laparotomy. Of the OA patients, 136 (67.0%) had one relaparotomy, while 67 (33.0%) underwent multiple reoperations. Compared to daytime cases, laparotomies performed overnight (6 pm-6 am) had more temporary closures with OA (42.8% OA vs. 57.2% PC, p = 0.04). When assessing by surgeon type, PC was performed in 78.7% of laparotomies by surgical subspecialties compared to 56.7% (p0.0001) of acute care surgeons. After propensity matching, OA patients had increased postoperative complications (71.2% vs. 41.4%, p0.0001), mortality (22.5% vs. 11.7%, p = 0.006), and longer median length of stay (13 vs. 9 days, p = 0.0001).Open abdomen was performed in 38.0% of patients, with one-third of those requiring multiple reoperations. Complications, mortality rates, and costs associated with OA were significantly increased when compared to PC. Given these findings, future studies are needed to determine appropriate indications for OA.Therapeutic/care management, level IV.

The American Society of Colon and Rectal Surgeons (ASCRS) is dedicated to assuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. The Clinical Practice Guidelines Committee is composed of Society members who ar

BACKGROUND:Despite improvement in technique and technology, using prophylactic ureteral catheters to avoid iatrogenic ureteral injury during colectomy remains controversial.OBJECTIVE:The aim of this study was to evaluate outcomes and costs attributable to prophylactic ureteral catheters with colecto

Background Patients with symptomatic severe aortic stenosis and a history of chest radiation therapy represent a complex and challenging cohort. It is unknown how transcatheter aortic valve replacement ( TAVR ) compares with surgical aortic valve replacement in this group of patients, which was the objective of this study. Methods and Results We retrospectively reviewed all patients with severe aortic stenosis who underwent either TAVR or surgical aortic valve replacement at our institution with a history of mediastinal radiation (n=55 per group). End points were echocardiographic and clinical outcomes in‐hospital, at 30 days, and at 1 year. Inverse propensity weighting analysis was used to account for intergroup baseline differences. TAVR patients had a higher STS score than surgical aortic valve replacement patients (5.1% [3.2, 7.7] versus 1.6% [0.8, 2.6], P P P TAVR patients (4.0 [2.0, 5.0] versus 6.0 [5.0, 8.0] days; P TAVR as was 30‐day mortality in inverse propensity weighting–adjusted Kaplan–Meier analyses. Conclusions In patients with severe aortic stenosis and a history of chest radiation therapy, TAVR performs better than predicted along with less adjusted 30‐day all‐cause mortality, postoperative atrial fibrillation, and shorter hospitalization compared with surgical aortic valve replacement. These data support further studies on the preferred role of TAVR in this unique patient population.

INTRODUCTION AND OBJECTIVES:Retrograde urethrogram (RUG) is a mainstay in the evaluation and diagnosis of urethral stricture disease. Despite this, minimal research exists comparing parameters foun...

Background The ACGME instituted duty hour restrictions in 2003. This presents a challenge for surgical residents who must acquire a medical and technical knowledge base during their training. Although the effect of work hour limitations on operative volume has been examined, no study has examined whether duty hour reform has had an effect on operative volume variability. Study Design The ACGME operative log data of graduating general surgery residents from 1992 to 2015 were examined. Residents with the most and fewest total major cases were identified and case logs, learning styles, and evaluations were analyzed. Statistical analysis was performed using linear regression analysis, chi-square test, Student's t -test, and Wilcoxon rank sum test. Significance was defined as p Results One hundred and thirty-five residents graduated from 1992 to 2015. No change in overall operative volume was seen after the 2003 duty hour reform, however, there was an increase in operative variability. In addition, there was an increase in the variability of total major cases between the resident completing the most and fewest cases per class (183.3; p = 0.02) after the start of work hour restrictions. The residents who graduated with the highest operative volume were more likely to be action-based learners (odds ratio = 6.81; 95% CI, 2.84–16.34; p Conclusions After the implementation of the 80-hour workweek, we found a significant increase in operative variability. This might suggest a growing disparity in the operative experience among surgical residents and, consequently, a varying quality of graduating residents. Programs should therefore consider using learning styles and developing competency-based training curricula to ensure equitable training among all trainees.

Hospital readmission has been identified by many payers as a surrogate for surgical quality. The 30-day readmission rate and factors associated with hospital readmission after restorative proctocolectomy with IPAA have not been well studied.The purpose of this work was to identify the rate of and factors associated with hospital readmission within 30 days of restorative proctocolectomy with IPAA.A retrospective review of patients undergoing IPAA from 2009 to 2012 in the University HealthSystem Consortium database was performed. Hospitals were stratified into quartiles according to the number of cases performed annually.This study was conducted using a national database of university hospitals.A total of 4952 patients within the 4-year study period were included in the analysis.The primary outcome measured was readmission within 30 days of discharge.The 30-day readmission rate was 22.8% overall, although high-volume centers performed significantly better than low-volume centers (high vs low volume: 19.7% vs 28.2%; p0.001). When controlling for confounding variables, multivariate analysis identified female sex (OR, 1.191; p = 0.02), government-based (vs private) insurance (OR, 1.364; p0.001), and higher preoperative severity of illness (OR, 1.491; p = 0.001) to be associated with readmission. In addition, a significant volume-dependent relationship on 30-day readmission was identified, wherein undergoing operation at the higher-volume hospitals was protective for predicting readmission. Hierarchical regression modeling indicated that 31% of the variation in readmission rates among individual hospitals was accounted for by hospital volume.This study was limited by its retrospective nature and limited postoperative complication data.The national 30-day readmission after IPAA creation was 22.8%, at least double that of other colorectal procedures. This high rate of readmission was mitigated by centers performing the highest volume of cases. Avoidance of referral to centers performing very few of these procedures annually may improve perioperative outcomes and reduce associated morbidity.

Precordial catch syndrome is a benign cause of chest pain in children and adolescents that remains underrecognized. Because of distinctive symptoms, precordial catch syndrome is not necessarily a diagnosis of exclusion. However, a detailed history eliciting diagnostic features is important, along with a physical examination excluding other pathologic disorders. We present the cases of 2 elite swimmers with asthma who had acute episodes of precordial catch syndrome, one associated with an acute asthma exacerbation and one not, while swimming during competitive swim meets that required rescue efforts for both and eventual evaluation in the emergency department.

Background: Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment. Methods: To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia. Results: The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = −0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo. Conclusions: The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.