Online informational bariatric seminars: increasing access to bariatric surgery or widening a divide?

BACKGROUND: Historically our institution has required prospective bariatric patients attend an in-person introductory seminar prior to their first clinic visit. Utilization of the internet has increased dramatically over the last 10 years and in 2016, we added an online seminar. With the emergence of COVID-19 and new rules regarding social distancing, we are currently relying exclusively on web-based orientation. Research suggests there are racial and socioeconomic disparities in the utilization of internet health resources in the general population. To our knowledge this has not been studied in regard to the bariatric population. METHODS: A retrospective chart review was performed on patients who attended online (OS) and in-person seminars (IPS). Our primary endpoint was to compare the percentage of patients who underwent surgery. Secondary outcomes included differences in demographic and clinical characteristics between the patients who attended the OS versus the IPS. RESULTS: Of the 1152 patients who attended a bariatric orientation, 71.2% scheduled an office visit. The IPS patients had a higher rate of office visits and shorter time between orientation and first visit. Of patients eligible for surgery, there was a higher percentage of Caucasians in the OS group while the IPS group had higher rates of Hispanic and African Americans. Patients from the OS group had higher rates of marriage and employment, and lower rates of medical co-morbidities. When controlling for age, sex, race/ethnicity, marital status, employment status and medical co-morbidities, there was no significant impact of type of orientation on progression to surgery. CONCLUSION: We found that there was no difference in progression to surgery between the two orientation groups. Importantly, however, we detected marked demographic and clinical differences between the two patient populations. There is an urgent need to address these disparities as we are now heavily relying on patient outreach and education via the internet.

Detection and potential consequences of intraoperative adverse events: A pilot study in the veterans health administration.

Surgical quality improvement efforts have focused on tracking and reducing postoperative mortality and morbidity. However, the prevalence of intraoperative adverse events (IAEs) and their association with postoperative surgical outcomes has been poorly studied. In this study, we detected IAEs using both retrospective chart review and prospective provider reporting. We then examined the association of IAEs with postoperative outcomes. The overall IAE detection rate per case was 0.7 and 0.07 (P < 0.0001) based on chart review and provider reporting, respectively. Types of IAEs varied between detection methods. Provider-reported IAEs were more serious, i.e., had a stronger association with 30-day postoperative complications than chart-identified IAEs (risk-adjusted odds ratios were 1.52 vs 1.02, respectively, both p < 0.0001). Our findings suggest that IAEs can be detected using either retrospective chart review or prospective provider reporting. However, provider reporting appears more likely to detect serious (albeit infrequent) IAEs compared to chart review.

Deficiency of the immunostimulatory cytokine IL-21 promotes intestinal neoplasia via dysregulation of the Th1/Th17 axis.

IL-21 has reported activity in promoting both Th1 and Th17 immune responses. Its role in sporadic human colorectal cancer is unknown. We aimed to delineate the role of IL-21 in a model of sporadic intestinal carcinogenesis. We found that in APCMIN/+ mice, ablation of IL-21 increased intestinal tumorigenesis. Expression of pro-inflammatory Th17-associated genes, including RORγt and IL-17A, was increased in the intestine in the absence of IL-21, while expression of antitumor Th1-associated genes Tbet, IFNγ, granzyme B, and perforin was decreased. Similarly, the IL-21-deficient APCMIN/+ mouse intestines had fewer infiltrating T cells as well as decreased effector memory T cells, NK cells, and granzyme B-expressing cells. Finally, our data suggest that IL-21 impairs Th17 immune responses as mesenteric lymph nodes from IL-21-deficient mice had increased IL-17A expression, and naive helper T cells from IL-21-deficient mice were more prone to differentiate into IL-17A-secreting cells.

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages.

Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1α, IL-6 and TNFα. Ccl2, Il1α and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1α and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20-CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1α and TNFα. Our findings support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.

Deficiency of IL-17A, but not the prototypical Th17 transcription factor RORγt, decreases murine spontaneous intestinal tumorigenesis.

While inflammation has been associated with the development and progression of colorectal cancer, the exact role of the inflammatory Th17 pathway remains unclear. In this study, we aimed to determine the relative importance of IL-17A and the master regulator of the Th17 pathway, the transcription factor RORγt, in the sporadic intestinal neoplasia of APC(MIN/+) mice and in human colorectal cancer. We show that levels of IL-17A are increased in human colon cancer as compared to adjacent uninvolved colon. Similarly, naïve helper T cells from colorectal cancer patients are more inducible into the Th17 pathway. Furthermore, IL-17A, IL-21, IL-22, and IL-23 are all demonstrated to be directly mitogenic to human colorectal cancer cell lines. Nevertheless, deficiency of IL-17A but not RORγt is associated with decreased spontaneous intestinal tumorigenesis in the APC(MIN/+) mouse model, despite the fact that helper T cells from RORγt-deficient APC(MIN/+) mice do not secrete IL-17A when subjected to Th17-polarizing conditions and that Il17a expression is decreased in the intestine of RORγt-deficient APC(MIN/+) mice. Differential expression of Th17-associated cytokines between IL-17A-deficient and RORγt-deficient APC(MIN/+) mice may explain the difference in adenoma development.

Associations of Socioeconomic Variables With Resection, Stage, and Survival in Patients With Early-Stage Pancreatic Cancer.

IMPORTANCE: Socioeconomic variables including sex, race, ethnicity, marital status, and insurance status are associated with survival in pancreatic cancer. It remains unknown exactly how these variables influence survival, including whether they affect stage at presentation or receipt of treatment or are independently associated with outcomes. OBJECTIVES: To investigate the relationship between socioeconomic factors and odds of resection in early-stage, resectable pancreatic adenocarcinoma and to determine whether these same factors were independently associated with survival in patients who underwent resection. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cohort study of patients diagnosed as having T1 through T3 M0 pancreatic adenocarcinoma between January 1, 2004, and December 31, 2011, identified from the Surveillance, Epidemiology, and End Results database. MAIN OUTCOMES AND MEASURES: Socioeconomic and geographic variables associated with utilization of resection and disease-specific survival. RESULTS: A total of 17,530 patients with localized, nonmetastatic pancreatic cancer were identified. The resection rate among these patients was 45.4% and did not change over time. Utilization of resection was independently associated with white vs African American race (odds ratio [OR] = 0.76; 95% CI, 0.65-0.88; P < .001), non-Hispanic ethnicity (for Hispanic, OR = 0.72; 95% CI, 0.60-0.85; P < .001), married status (OR = 1.42; 95% CI, 1.30-1.57; P < .001), insurance coverage (OR = 1.63; 95% CI, 1.22-2.18; P = .001), and the Northeast region (vs Southeast, OR = 1.67; 95% CI, 1.44-1.94; P < .001). Stage at presentation correlated with sex, race, ethnicity, marital status, and geographic region (ethnicity, P = .003; all others, P < .001); however, the factors associated with increased resection correlated with more advanced stage. Patients who underwent resection had significantly improved disease-specific survival compared with those who did not undergo resection (median, 21 vs 6 months; hazard ratio [HR] for disease-specific death = 0.32; 95% CI, 0.31-0.33; P < .001). Disease-specific survival among the patients who underwent surgical resection was independently associated with geographic region, with patients in the Pacific West (HR for death = 0.706; 95% CI, 0.628-0.793), Northeast (HR for death = 0.766; 95% CI, 0.667-0.879), and Midwest (HR for death = 0.765; 95% CI, 0.640-0.913) having improved survival in comparison with those in the Southeast (all P < .001). CONCLUSIONS AND RELEVANCE: Disparities in the utilization of surgical resection for patients with early-stage, resectable pancreatic cancer are associated with socioeconomic variables including race, ethnicity, marital status, insurance status, and geographic location. Of these factors, only geographic location is independently associated with survival in patients undergoing resection.

Trends and predictors of resection of the primary tumor for patients with stage IV colorectal cancer.

BACKGROUND AND OBJECTIVES: Over 130,000 patients are diagnosed with colorectal cancer annually, with approximately 20% presenting with unresectable metastatic disease. Recent consensus guidelines recommend against primary tumor resection for asymptomatic patients with unresectable metastases. Our goal was to examine the trends and predictors of surgical resection. METHODS: Cases of colorectal cancer with synchronous metastases diagnosed between 1988-2010 were identified using the Surveillance, Epidemiology and End Results (SEER) Database. Associations between resection and clinicopathologic variables were sought using univariate and multivariate logistic regression. RESULTS: Overall, 68% of patients with synchronous metastatic colorectal cancer underwent primary tumor resection. Resection rates were as high as 76% in the earliest time period (1988-1992) and steadily dropped to 60% in the most recent period (2008-2010). Socioeconomic factors associated with resection on univariate analysis included age, race, gender, marital status, insurance status, and geographic region. Clinicopathologic characteristics associated with resection included tumor location, grade, size, and CEA level. In the multivariate model, gender, geographic region, insurance status, tumor location, grade and CEA level were independent predictors of primary tumor resection. CONCLUSIONS: Surgical resection of the primary site remains common practice for patients with synchronous metastatic colorectal cancer. Treatment disparities are associated with socioeconomic as well as clinicopathologic factors.

Cytokine combination therapy with erythropoietin and granulocyte colony stimulating factor in a porcine model of acute myocardial infarction.

PURPOSE: Erythropoietin (EPO) and granulocyte colony stimulating factor (GCSF) have generated interest as novel therapies after myocardial infarction (MI), but the effect of combination therapy has not been studied in the large animal model. We investigated the impact of prolonged combination therapy with EPO and GCSF on cardiac function, infarct size, and vascular density after MI in a porcine model. METHODS: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. 16 animals were treated with EPO+GCSF, or saline (control group). Cardiac function was assessed by echocardiography and pressure-volume measurements at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. RESULTS: At week 6, EPO+GCSF therapy stabilized left ventricular ejection fraction, (41 ± 1% vs. 33 ± 1%, p < 0.01) and improved diastolic function compared to the control group. Histopathology revealed increased areas of viable myocardium and vascular density in the EPO+GCSF therapy, compared to the control. Despite these encouraging results, in a historical analysis comparing combination therapy with monotherapy with EPO or GCSF, there were no significant additive benefits in the LVEF and volumes overtime using the combination therapy. CONCLUSION: Our findings indicate that EPO+GCSF combination therapy promotes stabilization of cardiac function after acute MI. However, combination therapy does not seem to be superior to monotherapy with either EPO or GCSF.

Granulocyte colony stimulating factor in myocardial infarction with low ejection fraction.

BACKGROUND: We investigated the safety and efficacy of GCSF therapy in a porcine model of ischemia-reperfusion with left ventricle ejection fraction of <45% using a clinically relevant dosing and timing regimen. METHODS: MI was induced in pigs by a 90 min balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either GCSF (IV bolus of 10 microg/kg at time of reperfusion, followed by SC injections of 5 microg/kg days 5-9 post-MI) or saline (control group). Inflammatory markers, bone marrow cell mobilization and LV function (echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. Histopathology was performed 6 weeks post-MI. RESULTS: GCSF therapy was associated with a significant increase in white blood cell counts. At week 6, GCSF therapy resulted in less deterioration of LVEF compared to control (38+/-2% vs. 33+/-2%, p<0.02) and improved wall motion score index (p<0.05). Histopathology revealed increased vascular density (p<0.05) and a trend toward increased areas of viable myocardium compared to control (p=0.058). CONCLUSION: GCSF therapy prevents further deterioration of LV function in a porcine model of MI with lower EF (<45%). These results support future clinical trials with GCSF in selected patients with larger MI.

Prolonged therapy with erythropoietin is safe and prevents deterioration of left ventricular systolic function in a porcine model of myocardial infarction.

BACKGROUND: Erythropoietin (EPO) has generated interest as a novel therapy after myocardial infarction (MI), but the safety and efficacy of prolonged therapy have not been studied in a large animal model of reperfused MI. METHODS AND RESULTS: MI was induced in pigs by a 90-minute balloon occlusion of the left anterior descending coronary artery. Sixteen animals were randomized to either EPO or saline (control group). Inflammatory markers, bone marrow cell mobilization, and left ventricular function (by both echocardiography and pressure-volume measurements) were assessed at baseline, 1 and 6 weeks post-MI. EPO therapy was associated with a significant increase in hemoglobin and mononuclear counts. D-dimer and C-reactive protein levels did not differ between groups. At week 6, EPO therapy prevented further deterioration of left ventricular ejection fraction (39 +/- 2% vs. 33 +/- 1%, P < .01) and improved wall motion score index (P < .02). Histopathology revealed increased areas of viable myocardium, vascular density, and capillary-to-myocyte ratio in the EPO therapy compared with the control (all P < .05). CONCLUSION: Prolonged EPO therapy after MI in a large animal model is safe and leads to an increase in viable myocardium, increased vascular density, and prevents further deterioration of left ventricular function. These results support future clinical studies in post-MI patients.

Left ventricular remodeling after myocardial infarction: characterization of a swine model on beta-blocker therapy.

Current guidelines recommend beta blockers for patients after myocardial infarction (MI). Novel therapies for heart failure should be tested in combination with this medication before entering clinical trials. In this methodologic study, we sought to describe the time course of systolic and diastolic parameters of cardiac performance over a 6-wk period in closed-chest model of swine MI treated with a beta blocker. Myocardial infarction in pigs (n = 10) was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Echocardiography and pressure-volume data were collected before and at 1 and 6 wk after MI; histopathology was assessed at 6 wk. Left-ventricular (LV) volume increased significantly over 6 wk, with significant decreases in ejection fraction, wall motion index, stroke work, rate of pressure development (dP/dt(max)), preload recruitable stroke work, and mechanical efficiency. Impairment of diastolic function was manifested by a significant increase in the exponential beta coefficient of the LV end-diastolic pressure-volume relation and reduction of LV pressure decay. At 6 wk, histopathologic analysis showed that the size of the infarct area was 16.3% +/- 4.4%, and the LV mass and myocyte cross-sectional area in both the infarct border and remote zones were increased compared with those of noninfarcted pigs (n = 5). These findings suggest a dynamic pattern of remodeling over time in a closed-chest ischemia-reperfusion swine model of acute MI on beta-blocker therapy and may guide future studies.

Invasive left ventricular energetics during enhanced external counterpulsation.

Enhanced external counterpulsation (EECP) is a noninvasive technique that provides beneficial effects for patients with chronic, symptomatic angina pectoris. However, the direct left ventricular effects of EECP have not been studied invasively. We examined invasive right atrial pressure and left ventricular hemodynamics during EECP. Ten patients referred for diagnostic evaluation underwent left heart catheterization from the radial artery. At baseline and during EECP, left ventricular pressure and volume were measured using a micromanometer pressure-conductance catheter, along with recording of right atrial and central aortic pressures. Hemodynamics were recorded at different lower extremity cuff configuration and cuff inflation pressures. As cuff inflation pressure increased, EECP resulted in a dose-dependent increase in right atrial and aortic diastolic pressure (P < 0.0001). The increase in ventricular preload resulted in increased left ventricular volume. Maximum positive (P = 0.0003) and negative left ventricular dP/dt (P < 0.0001) increased. Left ventricular diastolic pressure decreased. There was a neutral effect on myocardial mechanical efficiency. In conclusion, EECP acutely increased right atrial and central aortic diastolic pressure. The increase in preload attenuated the reduction in left ventricular diastolic pressure resulting from systolic unloading. The increased preload counterbalanced the afterload reduction, resulting in a neutral effect on myocardial efficiency.

Echocardiographic predictors of change in left ventricular diastolic pressure in heart failure patients receiving nesiritide.

BACKGROUND: To evaluate the usefulness of currently accepted echocardiographic parameters of diastolic function to assess the acute change in left ventricular end-diastolic pressure (LVEDP) following the administration of nesiritide in a heart failure population. METHODS: In 25 heart failure patients (15 with systolic dysfunction, 10 with preserved ejection fraction [EF]), Doppler echocardiography, right and left heart catheterization, and invasive biventricular pressure hemodynamics were obtained at baseline and 30 minutes after nesiritide infusion. RESULTS: Twenty-four patients had sufficient echocardiographic images for analysis. The mean age was 60 +/- 11 years, 48% were male, 56% had coronary artery disease, and 64% had hypertension. Right ventricular systolic pressure (RVSP) had the highest correlation with LV filling pressure: pulmonary capillary wedge pressure (PCWP), pre-A wave LV, and LVEDP (r = 0.66, P = 0.0009; r = 0.63, P = 0.002; r = 0.72, P = 0.0002, respectively). Following nesiritide administration, the mean PCWP decreased from 17.1 +/- 7.8 mmHg at baseline to 9.6 +/- 6.2 mmHg (P < 0.001). Change in RVSP had the highest correlation with change in PCWP (r =-0.67, P = 0.10) and change in LVEDP (r =-0.71, P = 0.07). CONCLUSION: Echocardiographic parameters are frequently assessed in attempts to estimate left heart diastolic pressures. In heart failure patients, RVSP appears to be the best predictor of LVEDP, outperforming tissue Doppler E/E'. RVSP was found to be the best echocardiographic predictor of change in LV filling pressure with intravenous vasodilator therapy in heart failure patients. RVSP may provide a noninvasive means of assessing response to cardiac therapy.

The associations between tricuspid annular plane systolic excursion (TAPSE), ventricular dyssynchrony, and ventricular interaction in heart failure patients.

AIMS: Ventricular interactions may be mediated by loading conditions and biventricular timing and coordination. We sought to understand the relationships between right (RV) and left ventricular (LV) function and dyssynchrony, examine the RV correlates of LV dyssynchrony, and determine whether improved loading conditions affect inter-ventricular interaction. METHODS AND RESULTS: In 25 heart failure patients [15 with left ventricular ejection fraction (LVEF) < 40%; 10 with LVEF >/= 50%], Doppler echocardiography and invasive bi-ventricular pressure-volume haemodynamics were obtained at baseline and 30 min after infusion of the recombinant B-type natriuretic peptide vasodilator nesiritide. RV and LV intra-ventricular dyssynchrony was measured invasively using a pressure-conductance catheter. Patients with reduced LVEF had greater LV dyssynchrony (31 +/- 3 vs. 24 +/- 7%; P = 0.003) compared to those with preserved LVEF. Tricuspid annular plane systolic excursion (TAPSE) had the highest correlation with LV dyssynchrony (r = -0.52; P = 0.0002) compared to other RV echocardiographic parameters. The association between TAPSE and LV dyssynchrony was independent of RVEF and LVEF (P = 0.008). There were no acute changes in the correlations between LV dyssynchrony and TAPSE after nesiritide. CONCLUSION: TAPSE and LV dyssynchrony are strongly associated, independent of RV and LV ejection fraction. Of the RV echocardiographic parameters, TAPSE has the highest predictive value of LV dyssynchrony, and remained significant after vasodilator unloading.

Performance of phonoelectrocardiographic left ventricular systolic time intervals and B-type natriuretic peptide levels in the diagnosis of left ventricular dysfunction.

BACKGROUND: Systolic time intervals measured by echocardiography and carotid artery tracings are validated methods of assessing left ventricular function. However, the clinical utility of phonoelectrocardiographic systolic time intervals for predicting heart failure using newer technology has not been evaluated. METHODS: We enrolled 100 adult patients undergoing left heart catheterization. Participants underwent computerized phonoelectrocardiographic analysis, left ventricular end-diastolic pressure (LVEDP) measurement, transthoracic echocardiographic measurement of left ventricular ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. The heart rate-adjusted systolic time intervals included the time from the Q wave onset to peak S1 (electromechanical activation time, EMAT), Q wave onset to peak S2 (electromechanical systole, Q-S2), and peak S1 to peak S2 (left ventricular systolic time, LVST). Left ventricular dysfunction was defined as the presence of both LVEDP >15 mmHg and LVEF <50%. RESULTS: EMAT (r =-0.51; P < 0.0001), EMAT/LVST (r =-0.41; P = 0.0001), and Q-S2 (r =-0.39; P = 0.0003) correlated with LVEF, but not with LVEDP. An abnormal EMAT > or =15 (odds ratio 1.38, P < 0.0001) and EMAT/LVST > or =0.40 (OR 1.13, P = 0.002) were associated with left ventricular dysfunction. EMAT > or =15 had 44% sensitivity, 94% specificity, and a 7.0 likelihood ratio for left ventricular dysfunction, while EMAT/LVST > or =0.40 had 55% sensitivity, 95% specificity, and a 11.7 likelihood ratio. In patients with an intermediate BNP (100-500 pg/mL), the likelihood ratio increased from 1.1 using the BNP result alone to 11.0 when adding a positive EMAT test for predicting left ventricular dysfunction. CONCLUSIONS: Phonoelectrocardiographic measures of systolic time intervals are insensitive but highly specific tests for detecting abnormalities in objective markers of left ventricular function. EMAT and EMAT/LVST provide diagnostic information independent of BNP for detecting patients with left ventricular dysfunction.

Diagnostic characteristics of combining phonocardiographic third heart sound and systolic time intervals for the prediction of left ventricular dysfunction.

BACKGROUND: The third heart sound (S3) and systolic time intervals (STIs) are validated clinical indicators of left ventricular (LV) dysfunction. We investigated the test characteristics of a combined score summarizing S3 and STI results for predicting LV dysfunction. METHODS AND RESULTS: A total of 81 adults underwent computerized phonelectrocardiography for S3 and STI (Audicor, Inovise Medical Inc), cardiac catheterization for LV end-diastolic pressure (LVEDP), echocardiography for LV ejection fraction (LVEF), and B-type natriuretic peptide (BNP) testing. LV dysfunction was defined as both an LVEDP >15 mm Hg and LVEF <50%. The STI measured was the electromechanical activation time (EMAT) divided by LV systolic time (LVST). Z-scores for the S3 confidence score and EMAT/LVST were summed to generate the LV dysfunction index. The LV dysfunction index had a correlation coefficient of 0.38 for LVEDP (P = .0003), -0.53 for LVEF (P < .0001), and 0.35 for BNP (P = .0008). This index had a receiver operative curve c-statistic of 0.89 for diagnosis of LV dysfunction; a cutoff >1.87 yielded 72% sensitivity, 92% specificity, 9.0 positive likelihood ratio, and 88% accuracy. CONCLUSIONS: In this preliminary study, the LV dysfunction index combined S3 and STI data from noninvasive electrophonocardiography, and yielded superior test characteristics compared to the individual tests for the diagnosis of LV dysfunction.