Citations

Abstract Background: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. Methods: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). Results: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR=1.027, p=0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR=1.011, p<0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p=0.010 t-test), but tumor size was not correlated with female overall survival (p=0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p=0.004, F p=0.001, t-test). Additionally, extent of resection, tumor laterality, and IDH1 mutation status were also found to have sex-specific effects on overall survival. Conclusion: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

SUMMARY There is a strong evidence that Helicobacter pylori infection is inversely associated with Barrett's esophagus. In a high-prevalence region of H. pylori, low rates of esophageal cancer and its precursor BE may indicate its preventive effect. The aim of this study is to determine the impact of H. pylori on characteristics of Barrett's esophagus. A total of 3317 outpatient upper endoscopy reports from 2013 to 2015 from an urban center in Azerbaijan from all patients with dyspepsia were retrospectively analyzed for patients with Barrett's esophagus. This was matched in a 1:2 ratio to age and gender matched control patients without Barrett's esophagus. The prevalence of H. pylori on Barrett's esophagus and the randomly selected control group were compared. There were 83 patients with BE and 167 control group cases. Biopsy-proven BE was diagnosed in 83 patients: 39 (47%) females, with mean age 43.1 ± 13.3 years. Of these, 13 (15.7%) had long segment and 70 (84.3%) had short segment Barrett's esophagus. A control group included 167 patients: 78 (46.7%) females, with mean age (45.8 ± 13.9). All patients were Caucasians. The rates of gastric inflammation, the presence of atrophy, and intestinal metaplasia in gastric specimens did not differ in patients versus controls. The prevalence of H. pylori was determined as 63.2% in male and 61.5 in female groups (odd ratio (OR) = 0.99 95%CI 0.97, 1.01; P = 0.22). Inflammation of gastric mucosa was strongly associated with the infection (67% vs. 33%; OR = 4.46 95% CI: 2.01, 9.92, P &lt; 0.001). Atrophy was noted in majority of H. pylori-positive cases (OR = 1.43, 95% CI: 0.36, 5.65; P = 0.61). Gastric intestinal metaplasia was observed in 55.6% of H. pylori-positive patients and in 44.4% of negative individuals (OR = 0.74, 95% CI: 0.28, 1.94; P = 0.54). There was not a significant difference in the prevalence of HP in BE and control groups; 63.9% were positive for infection in BE cases and 61.7% of controls (OR = 1.10, 95% CI: 0.64, 1.90; P = 0.74). We found that neither presence of erosive esophagitis, length of BE nor dysplasia (45.5% of H. pylori-positive group, whereas 54.5%) was associated with the presence of the H. pylori infection (Table 1). In a predominantly Caucasian nation with a high prevalence of H. pylori gastritis, the presence of H. pylori was not inversely associated with the presence of Barrett's esophagus. These data challenge the mechanistic implications of this association.

Significance Statement Kidney stone recurrence can manifest with symptoms from stone passage or with asymptomatic changes in kidney stone burden revealed by radiography. In a multicenter, prospective cohort study, the authors demonstrate that substantially more asymptomatic and self-managed symptomatic kidney stone recurrence occur in stone formers than has been appreciated, as many studies consider only symptomatic recurrence that results in clinical care. Among first-time symptomatic stone formers, 54% had an asymptomatic kidney stone; half of those with such a stone passed it within 5 years (but only half who did so experienced symptoms). The findings also show that when a more comprehensive definition of recurrence that includes all symptomatic and radiological manifestations is used, risk factors better predict kidney stone recurrence, thus supporting a comprehensive assessment of recurrence in clinical trials. Background Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence. Methods We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors. Results Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation—symptomatic recurrence resulting in clinical care ( c -statistic, 0.63; 95% confidence interval, 0.52 to 0.73)—but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; c -statistic, 0.79; 95% confidence interval, 0.72 to 0.86). Conclusions Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.

AbstractBackgroundStudies have suggested transplantation using older donor livers results in similar short‐term outcomes as younger donor livers; however, little data exist on long‐term patient/graft outcomes of the octogenarian liver recipient.MethodsRetrospective data were collected from 2 centers, (Valencia, Spain and Rochester, MN, USA) of all recipients of octogenarian donor liver allografts from 2000 to 2011 with follow‐up to 2016. The aim was to compare long‐term patient/graft survival as well as metabolic outcomes of the recipient with the octogenarian liver vs younger than 60 years donor.Results78 recipients of older liver allografts were compared to 78 matched controls. No difference in 10‐year patient mortality was demonstrated (P = 0.074). Octogenarian livers were associated with 3‐fold higher likelihood of graft failure (P = 0.002) but no increase in the risk of post‐LT cardiovascular disease (P = 0.60), hypertension (P = 0.33), vascular complications (P = 0.53), or malignancy (P = 0.14). In multivariate analysis, elder livers remained a significant factor associated with rejection (P = 0.034) with a trend not reaching statistical significance for graft failure (P = 0.052).ConclusionsFor appropriately selected recipients, receiving an octogenarian liver does not clearly influence patient survival but does impact early graft survival with a notable increase in early posttransplant rejection rates and re‐transplantation. Over 1.5 decades, older allografts have not adversely affected metabolic outcomes.

Abstract Objective Several studies indicate that patients with primary hyperparathyroidism (PHPT) undergoing parathyroid surgery have improvement in mood and neuropsychological functioning. The current analysis aims to examine the relationship between biochemical and clinical variables and the improvement in depression scores and in specific symptoms, after parathyroidectomy. Design A prospective observational case‐control study at a referral centre. Patients Patients with PHPT undergoing parathyroidectomy (n = 88) or thyroid surgery (n = 85). Measurements The Patient Health Questionnaire‐9 (PHQ‐9) was utilized to obtain depression scores at enrolment and 12 months after surgery. The changes in PHQ‐9 were analysed and correlated with baseline clinical and biochemical parameters. Results At enrolment, there was no difference between the groups in the number with a depression diagnosis (PHPT 34.1%, thyroid surgery, 35.5%, P = 0.86). However, baseline PHQ‐9 scores were significantly higher in PHPT (median 7.5, range 0‐27) than thyroid surgery patients (median 3.0, range 0‐18, P < 0.0001). Following surgery, all PHQ‐9 scores, total and symptom group (cognitive, somatic) improved and were no longer different between PHPT (total PHQ‐9 median 2, range 0‐16) and thyroid (median 1, range 0‐14, P = 0.31) groups. Baseline parathyroid hormone level, but not calcium, had a weak relationship with change in PHQ‐9 score after parathyroid surgery ( P = 0.003). Baseline PHQ‐9 score was correlated with change in PHQ‐9 score at 12 months after parathyroid surgery ( P < 0.001). Conclusions Depression scores improve in both somatic and cognitive domains after parathyroidectomy for PHPT and baseline severity of depression predicts the response.

e13161 Background: Capturing family health history is a simple and cost-effective way to identify individuals at increased risk for hereditary cancers. Several barriers exist to family history collection in the clinical setting. Self-reported histories can be limited, inaccurate or static. Physicians are often overwhelmed with data and “alert fatigue.” These complex factors make it difficult to quantify hereditary risks. Patients with increased genetic predisposition may be missed and may not receive individualized cancer surveillance measures. Methods: A practice improvement project was implemented at Mayo Clinic Florida to enhance family history screening. A questionnaire and simple scoring algorithm were developed to prompt referral for genetic counseling. This tool was pilot tested in a multi-specialty gastroenterology clinic. The questionnaire was administered in the waiting room (tablet interface). Patients with significant risk factors identified were contacted and offered genetic counseling. Results: Currently, 291 patients have completed the questionnaire. Thirty of the 60 patients identified to have significant familial risk factors met with a genetic counselor. Of the twenty who completed genetic testing, 9 patients received one or more variants of unknown significance. Two pathogenic variants were identified. One patient was molecularly confirmed to have multiple endocrine neoplasia type 2, which can allow for cascade screening in her unaffected sibling. A pathogenic ATM variant was found in a patient with a recent personal history of pancreatic cancer. The result prompted consideration of platinum based chemotherapy and/or PARP inhibitors in her cancer management. She has had a visible response thus far with the treatment. Her sister implemented a new surveillance regimen after testing positive for the familial variant. Conclusions: Enhanced family history screening is a low cost, effective method for the identification of patients who may benefit from hereditary cancer screening and genetic testing. Increased attention to family history is a vital component of precision medicine in any care setting.

1079 Background: Brain metastases (BM) are a common and fatal complication of breast cancer but survival varies widely based on various prognostic factors (PF). Hence, patient counseling and therapeutic decisions should be individualized. We previously published a prognostic index (Breast GPA) based on cohort A (1985-2007, n = 642), updated it with tumor subtype in cohort B (1993-2010, n = 400) and are now updating it with a larger contemporary cohort (C). Methods: A multi-institutional (19) multi-national (3) retrospective database of 2473 breast cancer patients with BM diagnosed from 1/1/2006-12/31/2017 was created and compared to our prior cohorts. Demographic, clinical, molecular factors, tumor subtype and treatment were correlated with survival. Kaplan-Meier survival estimates were calculated and compared with log-rank tests. Results: The median survival (MS) for cohorts A, B and C improved over time [12, 14 and 16 mo, respectively ( < 0.01)] despite the subtype distribution becoming less favorable: Luminal B (ER/PR/HER2+) decreased from 26% to 21%; HER2 (HER2+/ER/PR-) decreased from 31% to 17%, Luminal A (ER/PR+/HER2-) increased from 20% to 31%; Basal (ER/PR/HER2-) was unchanged at 24%.MS by subtype improved from 21 to 27 mo in Luminal B, 18 to 25 mo in HER2, 10 to 14 mo in Luminal A and 6 to 9 mo in Basal tumors. The number of BM was 1 in 35%, ≤4 in 67% and > 10 in 18%. PF significant for survival were tumor subtype, age, KPS, number of BM and extracranial metastases (ECM) (all < 0.01). Surprisingly, Hispanic women (7%) showed improved survival (p < 0.01). BRCA1 was mutated in 57/533 (11%) and those patients showed a trend (0.16) toward improved survival. Treatment patterns have changed: the use of whole brain radiation therapy decreased from 71% to 67% to 47% in cohorts A, B and C, respectively. Conclusions: Despite the shift to less favorable tumor subtypes, MS has improvedbut varies widely by diagnosis-specific PF. Compared to prior cohorts, number of BM and ECM were identified as new PF. Ethnic, genetic and treatment differences between the eras are apparent. The updated Breast GPA, based on these data, and the correlation between BRCA1 and tumor subtype will be presented.

A reduction in intestinal barrier function is currently believed to play an important role in pathogenesis of many diseases, as it facilitates passage of injurious factors such as lipopolysaccharide, peptidoglycan, whole bacteria, and other toxins to traverse the barrier to damage the intestine or enter the portal circulation. Currently available evidence in animal models and in vitro systems has shown that certain dietary interventions can be used to reinforce the intestinal barrier to prevent the development of disease. The relevance of these studies to human health is unknown. Herein, we define the components of the intestinal barrier, review available modalities to assess its structure and function in humans, and review the available evidence in model systems or perturbations in humans that diet can be used to fortify intestinal barrier function. Acknowledging the technical challenges and the present gaps in knowledge, we provide a conceptual framework by which evidence could be developed to support the notion that diet can reinforce human intestinal barrier function to restore normal function and potentially reduce the risk for disease. Such evidence would provide information on the development of healthier diets and serve to provide a framework by which federal agencies such as the US Food and Drug Administration can evaluate evidence linking diet with normal human structure/function claims focused on reducing risk of disease in the general public.

Objectives: Midodrine is an α1-agonist approved for orthostatic hypotension. Recently, it has received attention as an oral vasopressor to facilitate ICU discharge. The purpose of this study was to identify the incidence of continuation of newly initiated midodrine upon ICU and hospital discharge and identify risk factors associated with its occurrence. Design: Single-center retrospective study. Setting: ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. Patients: Adult patients admitted to any ICU who received new midodrine for hypotension and survived to discharge. Interventions: None. Measurements and Main Results: During the study period, 1,010 patients were newly started on midodrine and survived to ICU discharge. Midodrine was continued in 67% (672/1,010) of patients at ICU discharge. Admission to cardiovascular surgery ICU and mixed medical/surgical ICU was a risk factor for midodrine continuation at ICU discharge (odds ratio, 3.94 [2.50–6.21] and 2.03 [1.29–3.20], respectively). At hospital discharge, 34% (311/909) of patients were continued on midodrine therapy. History of congestive heart failure predicted midodrine continuation at hospital discharge (odds ratio, 1.49 [1.05–2.12]). Hypertension and use of mechanical ventilation were associated with a decreased odds of midodrine prescription at both ICU and hospital discharge. Of those discharged from the ICU or hospital on midodrine, 50% were concomitantly prescribed antihypertensives. Discharge from the ICU on midodrine was associated with a significantly shorter ICU length of stay (7.5 ± 8.9 vs 10.6 ± 13.4 d) and reduced risk of in-hospital mortality (hazard ratio, 0.47 [95% CI, 0.32–0.70]; p < 0.001), despite no difference in baseline severity of illness scores. In contrast, patients discharged from the hospital on midodrine had a higher risk of 1-year mortality (hazard ratio, 1.60 [95% CI, 1.26–2.04]; p < 0.001). Conclusions: This study established a high prevalence of midodrine continuation in transitions of care. The risks and benefits of this practice remain unclear. Future studies should explore the impact of this practice on patient outcomes and resource utilization. These insights could be used to model interventions for proper tapering, discontinuation, or follow-up of new start midodrine.