Proton Pump Inhibitor Therapy in Eosinophilic Esophagitis: Predictors of Nonresponse

Ryan Alexander, Jeffrey A Alexander et al.

Dig Dis Sci. 2020 Sep 29 [Epub ahead of print]

BACKGROUND Identification of clinical predictors of response to first-line therapies for EoE is needed to guide initial medical management.

STUDY DESIGN A retrospective analysis of patients diagnosed with EoE from 2011 to 2018 was conducted. Clinical and diagnostic variables including demographics, endoscopic, and esophagram findings were compared between PPI responders and PPI nonresponders. All patients underwent a standard 8-week twice-daily PPI trial, with PPI responsiveness defined as < 15 eos/hpf on repeat EGD. Univariate and multivariable analyses were conducted to identify risk factors for nonresponse, and ROC curves were created to identify cutoff values.

RESULTS A total of 223 EoE patients (135 male, median age 39 (29-51)) were identified, with PPI nonresponse (PPI-NR) in 71% of patients. PPI-NR was seen in all 10 patients with failure of scope passage, with an OR of 9.06 by univariate analysis (P = 0.1485). In a multivariable model, age per 10 years (OR 0.71; P = 0.007), BMI per 1 kg/m 2 (OR 0.94; P = 0.03), and peripheral eosinophil count per 100 per mm 3 (OR 1.37; P = 0.003) were independent risk factors. Dichotomization to maximize sensitivity and specificity identified age ≤ 36 years old, BMI ≤ 25.2 kg/m 2 , and peripheral eos > 460 per mm 3 as predictive thresholds for PPI-NR. The probability of PPI-NR was 72.4-84.5% with 1 risk factor, 87.9-93.8% with 2 risk factors, and 97.2% with all 3 risk factors.

CONCLUSIONS Young age, reduced BMI, elevated peripheral eosinophil count, and likely inability to pass an endoscope predict lack of response to PPIs in patients with EoE.

Gastric bypass induces diabetes remission in obese patients

WASHINGTON (IMNG) – Gastric bypass surgery resulted in significantly more weight loss and also improved measures of glycemic control significantly more than did other forms of bariatric surgery, Dr. John Morton reported at the annual clinical congress of the American College of Surgeons.

However, he noted, while remission did correlate with weight loss in patients who had gastric banding or sleeving, it appeared to be independent of weight loss in those who had the bypass surgery. While he didn’t speculate on the reasons for this finding, he did affirm his belief that gastric bypass is the best option for most obese patients with comorbid diabetes.

“I feel very comfortable recommending it” for these patients, said Dr. Morton of the Stanford (Calif.) University. “There are, of course, other clinical conditions to consider when deciding [among] bypass, banding, and sleeve, but if the only consideration is around diabetes, I’m 100% comfortable in recommending it for obese diabetics.”

He presented the 1-year follow-up data on 1,792 obese patients who underwent bariatric surgery. Of these, 1,364 had a Roux-en-Y bypass; 264 had a sleeve gastrectomy; and 164 had adjustable gastric banding.

The patients were a mean of about 46 years old. Body mass index was statistically, but not clinically, different between the groups (bypass 47 kg/m2; band 44 kg/m2; sleeve 44 kg/m2). Waist circumference ranged from 51 to 53 inches. About 75% of the group was female and more than half, white.

Overall, about one-third of each group had type 2 diabetes. Most were taking only oral medications. About 5% took only insulin, and about a quarter took both oral agents and insulin. At baseline, the mean HbA_1c was more than 7% in each group. The mean fasting insulin was 36 microU/mL in the bypass group, 28 microU/mL in the band group, and 32 microU/mL in the sleeve group.

By 12 months after surgery, patients with diabetes who had bypass had lost the most weight – a mean of 71% of their excess body weight, compared with 38% in the banding group and 50% in the sleeve group.

Those who had the bypass surgery also experienced the biggest change in their HbA_1c – dropping almost 16% to a mean of 5.8%. Patients in the other two groups experienced a mean drop of 10%, resulting in HbA_1c levels of right around 6%.

Fasting insulin levels also improved significantly more in the bypass group, falling from a baseline mean of 56 microU/mL to 7.8 microU/mL – a decrease of 68%. In the band group, the level fell from 28 microU/mL to 12 microU/mL – a 52% decrease. In the sleeve group, levels fell from 32 microU/mL to 10 microU/mL – a 61% decrease.

“Fasting insulin is also considered an independent marker of cardiac risk,” Dr. Morton added, indicating that the risk of cardiovascular problems would fall along with insulin levels.

Blood glucose improved significantly more in the bypass group, falling from a baseline mean of 149 mg/dL to 101 mg/dL – a 22% change. In the band group, the level fell from 140 mg/dL to 125 mg/dL (8%) and in the sleeve group, from 130 mg/dL to 118 mg/dL (5.6%).

A multivariate analysis controlled for surgery type, sex, body mass index, race, age, and insurance status. Of these factors, surgery type was the strongest predictor, with bypass patients three times more likely to achieve that goal than those undergoing banding or sleeve placement.

Dr. Morton did not present his complication data. However, during the discussion period, he said the three procedures were similarly safe. The gastric sleeve group had a higher leak rate than did the other groups, but that remained less than 1%. Readmission rates were comparable, he said, but he did not provide that number.

“Any time you consider this, it has to be a risk/benefit analysis,” he said. “It’s our philosophy that for obese patients with severe diabetes, we approach them first with the bypass because it has the most proven track record over time.”

Dr. Morton has up to 7 years of data on some of the patients, and said he is now analyzing that. But when questioned about durability, he agreed that diabetes can recur in the rather common scenario of a patient regaining weight. “At the end of the day, though, what’s important is that the obese patient with diabetes gets treatment. All three surgeries demonstrated some improvement, and I believe that any surgery is better than no surgery at all.”

Dr. Morton has received research support from Covidien.

Can the Experience of Discrimination Increase Hypertension Risk?

New insights from the Jackson Heart Study link lifetime discrimination and risk for hypertension in African-Americans.

In the U.S., Black people bear a greater burden of hypertension than any other racial or ethnic group. Investigators hypothesized that beyond traditional risk factors, the experience of discrimination contributes to higher hypertension prevalence and tested the hypothesis by analyzing data on 1845 African-American participants without baseline hypertension from the Jackson Heart Study, the longitudinal investigation of genetic and environmental risk factors associated with the disproportionate burden of cardiovascular disease in African-Americans.

Experience of discrimination was measured at visit 1 by two validated scales measuring lifetime and everyday discrimination. Of the [participants], 954 (52%) developed hypertension during follow-up. After adjustment for traditional cardiovascular risk and socioeconomic factors such as education, income, and occupation, individuals who reported medium-to-high levels of lifetime discrimination were more likely to develop hypertension than participants reporting low discrimination levels. No association was found between everyday discrimination and incident hypertension. In sex-stratified analyses, the association between lifetime discrimination and incident hypertension was observed only in women.

COMMENT

These study results suggest that discrimination might be an important contributor to the glaring disparities in hypertension experienced by African-American women. Discrimination was measured with validated survey instruments, but only at one point in time; however, it is likely that discrimination experiences are dynamic and thus incompletely captured cross-sectionally. More work is needed to see how interventions to combat discrimination affect cardiovascular risk in African-American communities.

Fatima Rodriguez, MD, MPH, FACC, FAHA reviewing Forde AT et al. Hypertension 2020 Jul 1

CITATION(S):

Forde AT et al. Discrimination and hypertension risk among African Americans in the Jackson Heart Study. Hypertension 2020 Jul 1; [e-pub].

[PubMed® abstract]