Prevalence and Demographic Profiles of Food Insecure College Students at Main and Satellite Campuses in Northwestern USA.

Background: Recent studies demonstrated that food insecurity rates among college students surpass that of the general population. Both academic and health implications have been associated with food insecurity. Aim: This study compared the prevalence of food insecurity among students at three satellite campuses with those at the main campus of a 4-year, public university. Methods: In this cross-sectional design study, data were collected for four weeks using an anonymous, online questionnaire (10 demographic questions plus the USDA's Adult Food Security Survey 10-item module). A sample of 983 students was recruited from the 9064 undergraduate and graduate students attending a state university. Chi-square tests were used to assess demographic differences between food insecure students on the main and satellite campuses. Logistic regression was performed to evaluate the odds of food insecurity by campus (satellite vs. main), after controlling for demographics. Statistical significance was assessed at P < 0.05. Results: Bivariate results indicated the rate of food insecurity was significantly higher on the main campus (45%) than on the satellite campuses (34%, P = 0.007). However, after controlling for demographics there was no difference in the odds of food insecurity by campus (P = 0.239). Conclusion: The study findings are novel as no other studies compared the prevalence of food insecurity among students attending satellite campuses compared with those at the main campus. After controlling for demographics, type of campus (satellite vs. main) was not a significant factor in the odds of food insecurity.

'Pain-free TRUS B': a phase 3 double-blind placebo-controlled randomized trial of methoxyflurane with periprostatic local anaesthesia to reduce the discomfort of transrectal ultrasonography-guided prostate biopsy (ANZUP 1501).

OBJECTIVE: To determine whether the addition of inhaled methoxyflurane to periprostatic infiltration of local anaesthetic (PILA) during transrectal ultrasonography-guided prostate biopsies (TRUSBs) improved pain and other aspects of the experience. PATIENTS AND METHODS: We conducted a multicentre, placebo-controlled, double-blind, randomized phase 3 trial, involving 420 men undergoing their first TRUSB. The intervention was PILA plus a patient-controlled device containing either 3 mL methoxyflurane, or 3 mL 0.9% saline plus one drop of methoxyflurane to preserve blinding. The primary outcome was the pain score (0-10) reported by the participant after 15 min. Secondary outcomes included ratings of other aspects of the biopsy experience, willingness to undergo future biopsies, urologists' ratings, biopsy completion, and adverse events. RESULTS: The mean (SE) pain scores 15 min after TRUSB were 2.51 (0.22) in those assigned methoxyflurane vs 2.82 (0.22) for placebo (difference 0.31, 95% confidence interval [CI] -0.75 to 0.14; P = 0.18). Methoxyflurane was associated with better scores for discomfort (difference -0.48, 95% CI -0.92 to -0.03; P = 0.035, adjusted [adj.] P = 0.076), whole experience (difference -0.50, 95% CI -0.92 to -0.08; P = 0.021, adj. P = 0.053), and willingness to undergo repeat biopsies (odds ratio 1.67, 95% CI 1.12-2.49; P = 0.01) than placebo. Methoxyflurane resulted in higher scores for drowsiness (difference +1.64, 95% CI 1.21-2.07; P < 0.001, adj. P < 0.001) and dizziness (difference +1.78, 95% CI 1.31-2.24; P < 0.001, adj. P < 0.001) than placebo. There was no significant difference in the number of ≥ grade 3 adverse events. CONCLUSIONS: We found no evidence that methoxyflurane improved pain scores at 15 min, however, improvements were seen in patient-reported discomfort, overall experience, and willingness to undergo repeat biopsies.

Fruit and Vegetable Prescription Program for Diabetes Control Among Community Health Centers in Rural Idaho and Oregon.

A Fruit and Vegetable Prescription program (12-16 weeks, 2018-2020) was implemented at community health centers serving rural communities in the northwestern United States. The impact of the program on type 2 diabetes control was evaluated. Reductions in mean hemoglobin A1C were statistically significant (P < .01). The percentage of participants with critically high blood glucose levels (A1C > 9%) decreased from 76% (114/151) to 41% (62/151; P < .01). The findings mirror those of similar programs. The sustainability of these beneficial interventions, however, relies on improved access to preventive care. (Am J Public Health. 2022;112(7):975-979.https://doi.org/10.2105/AJPH.2022.306853).

Perceptions of dietary factors promoting and preventing nephrolithiasis: a cross-sectional survey.

OBJECTIVE: To assess knowledge of both promoting and preventive dietary factors on nephrolithiasis in a diverse patient population. Precipitating factors of kidney stone disease include diet, lifestyle, socioeconomic status, and race/ethnicity. However, patient awareness of these influences is poorly described. MATERIALS AND METHODS: A 24-question survey, assessing intake-related risk factors for stone disease, was administered prospectively to 1018 patients. Responses were summarized with frequency and percent. Statistical comparisons were made using a propensity scoring method in order to account for potential confounding variables. Propensity scores were stratified into quintiles. Further analysis with multiple imputation was performed to account for any missing data in the survey. The results of the propensity-adjusted log-binomial regression model are presented as prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: Respondents demonstrated limited knowledge of nutrient factors that influence stone development. However, most study participants (70.3%) reported a willingness to make lifestyle changes aimed at lowering their risk for stone disease. Respondents reporting previous nephrolithiasis education were less likely to report that diet had no effect on kidney stone formation (PR = 0.795, 95% CI 0.65, 0.96, p = 0.01) The type of physician who counseled the respondent had no association with patient knowledge for stone disease (PR = 0.83, 95% CI 0.63, 1.10, p = 0.2). CONCLUSIONS: Knowledge of diet-related risk factors for nephrolithiasis is limited among this population. Respondents who received prior education appeared to maintain the knowledge of dietary risk for nephrolithiasis. Participants also expressed a willingness to make requisite dietary changes if that information is provided. Given that most stone formers experience a recurrence, these findings highlight the need for more comprehensive patient education strategies on the modifiable risk factors for nephrolithiasis.

World Cafés Create Healthier Communities for Rural, Older Adults Living With Diabetes.

Our global population is aging at an accelerated pace. While the average life expectancy has seen dramatic increases, chronic disease and disability have also increased, with rural America tending to be older, sicker, and poorer. This article examines the implementation and outcomes associated with the community engagement method of the world café that was instrumental in developing a "culture of health" aimed to reduce diabetes-related inequalities for older adults in rural counties of Kentucky. Older residents and the organizations that serve them participated in world cafés, which resulted in collective action due to the wisdom and capacity that evolve from the core element of the method, conversational sharing via multiple small group interactions. Four world cafés were held to explore the desires of the communities related to healthy eating, exercise, smoking cessation, and diabetes care. The world cafés brought a diverse group of community residents and governmental and business leaders to discuss topics that matter to their community, leading to the development of a strategic plan and a scorecard and, ultimately, community empowerment.

Novel pathogenic variants in FOXP3 in fetuses with echogenic bowel and skin desquamation identified by ultrasound.

Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome is a rare, X-linked recessive disease that affects regulatory T cells (Tregs) resulting in diarrhea, enteropathy, eczema, and insulin-dependent diabetes mellitus. IPEX syndrome is caused by pathogenic alterations in FOXP3 located at Xp11.23. FOXP3 encodes a transcription factor that interacts with several partners, including NFAT and NF-κB, and is necessary for the proper cellular differentiation of Tregs. Although variable, the vast majority of IPEX syndrome patients have onset of disease during infancy with severe enteropathy. Only five families with prenatal presentation of IPEX syndrome have been reported. Here, we present two additional prenatal onset cases with novel inherited frameshift pathogenic variants in FOXP3 that generate premature stop codons. Ultrasound findings in the first patient identified echogenic bowel, echogenic debris, scalp edema, and hydrops. In the second patient, ultrasound findings included polyhydramnios with echogenic debris, prominent fluid-filled loops of bowel, and echogenic bowel. These cases further broaden the phenotypic spectrum of IPEX syndrome by describing previously unappreciated prenatal ultrasound findings associated with the disease.

Long-term observation of a patient with dominant omodysplasia.

We report on the natural history of a female with dominant omodysplasia, a rare osteochondrodysplasia with short stature, rhizomelia of the extremities (upper extremities more affected), and short first metacarpals. The proband had normal molecular analysis of the glypican 6 gene (GPC6), which was recently reported as a candidate for autosomal recessive omodysplasia. The findings in this patient were compared to other known and suspected cases of autosomal dominant omodysplasia. Mild rhizomelic shortening of the lower extremities has not been previously reported.

FlourishCare Model of Integrated Care: The Validation of the Flourish Index-Revised.

BACKGROUND AND OBJECTIVES: This study validates the Flourish Index-Revised (FI-R), a tool evaluating integrated healthcare models. The original Flourish Index (FI) was developed in 2018 and has been refined to align with the FlourishCare (FC) Model (Model) for geriatric primary care. RESEARCH DESIGN AND METHODS: The Model provides integrated biopsychosocial healthcare to older adults. The FI-R uses 25 quality-of-care indicators and 7 contextual community indicators. The FI-R was validated with Categorial Principal Components Analysis (CATPCA) using a sample of 949 patients 50+ who were mostly female (73%), non-Hispanic White (70%), living in urban areas (90%), and married (29%), single (22%), or divorced (19%). The mean age was 73.46 (standard deviation [SD] = 10.86) and mean years of education was 14.30 (SD = 2.14). RESULTS: CATPCA showed a 4-dimensional structure of biological, psychological, and 2 social determinants of health (SDOH) subdomains: health behaviors and community. Final selection of indicators was based on total variance accounted for >0.30, absolute values of item loadings >0.45, and not having cross-loadings >0.45 on 2 factors. Internal consistency (Cronbach's alpha) for the determinants were biological = 0.75, psychological = 0.76, SDOH:community = 0.70, SDOH:health behaviors = 0.50, and total FI-R = 0.95. Sensitivity to change was shown for the total FI-R, psychological determinants, and SDOH:health behaviors, but not for biological determinants. DISCUSSION AND IMPLICATIONS: The validation of the FI-R shows promise for its usability to evaluate integrated healthcare models using existing measures in electronic health systems. More work is needed to improve the incorporation of SDOH:sociodemographics into the FI-R.

Agents of Change: Geriatrics Workforce Programs Addressing Systemic Racism and Health Equity.

Many factors affect how individuals and populations age, including race, ethnicity, and diversity, which can contribute to increased disease risk, less access to quality healthcare, and increased morbidity and mortality. Systemic racism-a set of institutional policies and practices within a society or organization that perpetuate racial inequalities and discrimination-contributes to health inequities of vulnerable populations, particularly older adults. The National Association for Geriatrics Education (NAGE) recognizes the need to address and eliminate racial disparities in healthcare access and outcomes for older adults who are marginalized due to the intersection of race and age. In this paper, we discuss an anti-racist framework that can be used to identify where an organization is on a continuum to becoming anti-racist and to address organizational change. Examples of NAGE member Geriatric Workforce Enhancement Programs (GWEPs) and Geriatrics Academic Career Awards (GACAs) activities to become anti-racist are provided to illustrate the framework and to guide other workforce development programs and healthcare institutions as they embark on the continuum to become anti-racist and improve the care and health of vulnerable older adults.

Clinical utility of the X-chromosome array.

Previous studies have limited the use of specific X-chromosome array designed platforms to the evaluation of patients with intellectual disability. In this retrospective analysis, we reviewed the clinical utility of an X-chromosome array in a variety of scenarios. We divided patients according to the indication for the test into four defined categories: (1) autism spectrum disorders and/or developmental delay and/or intellectual disability (ASDs/DD/ID) with known family history of neurocognitive disorders; (2) ASDs/DD/ID without known family history of neurocognitive disorders; (3) breakpoint definition of an abnormality detected by a different cytogenetic test; and (4) evaluation of suspected or known X-linked conditions. A total of 59 studies were ordered with 27 copy number variants detected in 25 patients (25/59 = 42%). The findings were deemed pathogenic/likely pathogenic (16/59 = 27%), benign (4/59 = 7%) or uncertain (7/59 = 12%). We place particular emphasis on the utility of this test for the diagnostic evaluation of families affected with X-linked conditions and how it compares to whole genome arrays in this setting. In conclusion, the X-chromosome array frequently detects genomic alterations of the X chromosome and it has advantages when evaluating some specific X-linked conditions. However, careful interpretation and correlation with clinical findings is needed to determine the significance of such changes. When the X-chromosome array was used to confirm a suspected X-linked condition, it had a yield of 63% (12/19) and was useful in the evaluation and risk assessment of patients and families.

Interstitial cystitis patients' use and rating of complementary and alternative medicine therapies.

INTRODUCTION AND HYPOTHESIS: The purpose of this study was to describe the use of complementary and alternative medicine (CAM) therapies among interstitial cystitis (IC) patients, patients' perception of CAM therapies' effectiveness, and the association of time since diagnosis with perceived effectiveness of these therapies. METHODS: In April 2009, the Interstitial Cystitis Association (ICA) initiated an Internet-based survey on CAM. Respondents indicated whether they received an IC diagnosis and how long ago, whether they tried CAM, and who recommended it. On a 5-point scale, respondents rated 49 therapies. For respondents confirming a diagnosis, we used a chi-square goodness-of-fit test to assess which therapies were rated positively or negatively by a majority of patients who tried them. Using separate one-way analyses of variance, we assessed differences in mean perceived effectiveness among groups based on time since diagnosis and conducted post hoc tests, if necessary. Using chi-square tests, we explored the association of time since diagnosis with the use of CAM and the number of therapies tried. RESULTS: A total of 2,101 subjects responded to the survey; 1,982 confirmed an IC diagnosis. Most (84.2 %) had tried CAM, and 55 % said physicians had recommended CAM. Of those trying CAM, 82.8 % had tried diet or physical therapy and 69.2 % other therapies. Of the therapies, 22 were rated positively and 20 negatively; 7 were inconclusive. Therapies patients perceived to be helpful included dietary management and pain management adjuncts such as physical therapy, heat and cold, meditation and relaxation, acupuncture, stress reduction, exercise, and sleep hygiene. Many therapies worked better for those diagnosed recently than for those diagnosed long before. CONCLUSIONS: Randomized, placebo-controlled studies are needed to demonstrate which therapies may indeed control IC symptoms and help send research in new and productive directions.

Nutritional Considerations for Bladder Storage Conditions in Adult Females.

BACKGROUND: Clinical guidelines developed by urologic, urogynecologic, and gynecologic associations around the globe include recommendations on nutrition-related lifestyle and behavioral change for bladder storage conditions. This study identified and compared clinical guidelines on three urological conditions (interstitial cystitis/bladder pain syndrome (IC/BPS), overactive bladder, and stress urinary incontinence) affecting adult women. METHODS: A three-step process was employed to identify the guidelines. Next, a quality assessment of the guidelines was conducted employing the Appraisal of Guidelines Research and Evaluation (AGREE II) International tool. (3) Results: Twenty-two clinical guidelines, prepared by seventeen groups spanning four continents, met the inclusion criteria. The AGREE II analyses revealed that most of the guideline development processes complied with best practices. The most extensive nutrition recommendations were for women with IC/BPS. Dietary manipulation for the other two storage LUTS primarily focused on the restriction or limitation of specific beverages and/or optimal fluid intake. (4) Conclusion: Clinical guidelines for IC/BPS, overactive bladder, and stress urinary incontinence include nutrition recommendations; however, the extent of dietary manipulation varied by condition. The need to ensure that clinicians are informing patients of the limitations of the evidence supporting those recommendations emerged. Furthermore, given the need to treat nutrition-related comorbid conditions as a strategy to help mitigate these three urological disorders, the value of referral to a dietitian for medical nutrition therapy is apparent.

Community Engagement in Research: An Updated Systematic Review of Quantitative Engagement Measurement Scales for Health Studies.

Though the interest in community engagement in research (CEnR) protocols has increased, studies reporting on the findings of tested CEnR engagement measurement scales for health studies are sparse. A systematic review was conducted from January 1 to March 1, 2023, to identify validated, quantitative CEnR engagement measurement tools for health studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was employed. The rigor of scale development, testing, and implementation was explored, and a `best practices evaluation conducted. Themes on the readiness of scales for implementation in health research studies were narratively compiled. Nineteen studies met the search inclusion criteria-reporting on the development, testing, and implementation of seven CEnR engagement measurement scales for health studies. Scale implementation studies precipitated only two of the studies. None of the scales followed the rigorous process dictated in best practices; however, at this time, three scales have gone through the most robust testing processes. Advancement of the science of engagement measurement requires consensus on terminology, application of best practices for scale development and testing protocols, and consistency of reporting findings.

Leveraging Telehealth for Delivery of Palliative Care to Remote Communities: A Rapid Review.

Background: Palliative care encompasses supportive health care for patients at any stage of illness aimed at relieving symptoms, controlling pain, managing stress, offering respite for caregivers, and optimizing the quality of life. Objective: To explore strategies for increasing access to palliative care among individuals living in remote/rural communities, a rapid review was conducted on studies that explored the use of telehealth applications with this population. Methods: From December 2019 to February 2020, the PRISMA methodology was used to gather peer-reviewed studies published in the English language. MedLine, Google Scholar, and EBSCO were searched; no date limitations were set. Given the diversity of study methodologies and outcomes, the findings were synthesized narratively. The Cochrane Collaboration's tool for assessing the risk of bias was also employed. Lastly, the studies were mapped to clinical guidelines for the various aspects of quality palliative care. Results: The 18 studies found, published between 2004 and 2019, were conducted in seven countries and on five continents. Aims included evaluating feasibility, efficacy, and user satisfaction. Insights draw from a combined pool of 3,313 patients and 250 providers. Most studies involved oncology patients and employed videoconferencing or a web platform/online software with videoconferencing. Three themes emerged: delivery of care, symptom management and quality of life, and patient/caregiver/provider satisfaction levels. Telehealth proved effective for patient and medication monitoring, provider and specialist appointments, and palliative care consultations. Operational benefits included clinician time saved, shorter appointment wait times, and reduced no show rates; implementation challenges also emerged. Statistical improvements in quality of life and symptom management were reported. Nearly two-thirds of the studies reported positive experiences among patients, caregivers, and providers; about half included an interprofessional team. The studies primarily focused on the structure/process and physical aspects of quality palliative care, there was a paucity of insights on the spiritual, cultural, end of life, and ethical/legal aspects of care. Two-thirds (12/18) of the studies employed a descriptive design. Risk for selection, performance, detection, and reporting biases emerged for all the studies; for example, only four of the studies included control groups and less than 20% (3/18) reported on attrition of study participants. Additional limitations include the rapid review methodology which relied heavily on the lead author's decisions and the restriction of studies published only in the English language. Conclusion: More rigorous research is required to confirm the viability of clinical care delivery and establish best practices for quality, virtual palliative care to remote/rural areas.

Food Insecurity among a Cohort of Division I Student-Athletes.

Background: Though the vulnerability of college students to food insecurity is well established, there is a paucity of studies focusing on the prevalence of food insecurity among student-athletes. Methods: A cross-sectional survey was conducted with collegiate athletes in the northwestern United States via an anonymous online survey. Food security status was assessed using the 10-item US Department of Agriculture Adult Food Security Survey. Results: Participating athletes (45/307, 14%) were primarily White, non-Hispanic (78%) females (73%) who lived and consumed meals off-campus (62% and 69%, respectively). Food insecurity was more prevalent among collegiate athletes than the general university population, 60% vs. 42%, respectively. Being a track or football athlete significantly predicted food security status (p = 0.002, p < 0.001, respectively). The risk for food insecurity was higher among collegiate football players (effect size, η2 = 0.86) compared with track athletes (effect size, η2 = 0.40). Conclusion: A statistically significant risk for food insecurity emerged among members of the football team. Factors contributing to disparate rates of food insecurity among college populations were explored and unique considerations for collegiate athletes discussed.

Anti-Inflammatory Diet for Women with Interstitial Cystitis/Bladder Pain Syndrome: The AID-IC Pilot Study.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by pelvic pain coupled with urinary frequency and urgency. The underlying cause of IC/BPS is unknown; there is no cure. Dietary components exacerbate symptoms. The Anti-Inflammatory Diet for Interstitial Cystitis (AID-IC) employs a randomized, crossover design to evaluate the effect of a plant-based, low saturated fat diet on the quality of life of women with IC/BPS. Insights on the implementation of the protocol and reflections on the facilitators and barriers experienced during the pilot study follow. The logistics of the protocol proved time-consuming; however, the barriers were surmountable. Quantitative and qualitative findings suggest that the AID-IC therapeutic diet may have lessened symptoms and improved the quality of life for many of the women in the study.

AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

GDP-mannose transporter paralogues play distinct roles in polarized growth of Aspergillus nidulans.

GDP-mannose transporters (GMT) carry GDP-mannose nucleotide sugars from the cytosol across the Golgi apparatus membrane for use as substrates in protein glycosylation in plants, animals and fungi. Genomes of some fungal species, such as the yeast Saccharomyces cerevisiae, contain only one gene encoding a GMT, while others, including Aspergillus nidulans, contain two (gmtA and gmtB). We previously showed that cell wall integrity and normal hyphal morphogenesis in A. nidulans depend upon the function of GmtA and that GmtA localizes to a Golgi-like compartment. Cells bearing the calI11 mutation in gmtA also have reduced cell surface mannosylation. Here we show that GmtB colocalizes with GmtA, suggesting that the role of GmtB is similar to that of GmtA, although the respective transcript levels differ during spore germination and early development. Transcript levels of gmtB are high in ungerminated spores and remain so throughout the first 16 h of germination. In contrast, transcript levels of gmrtA are negligible in ungerminated spores but increase to levels comparable to those of gmtB during germination. These observations suggest that although GmtA and GmtB reside within the same subcellular compartments, they nevertheless perform distinct functions at different stages of development.

Effect of Morning vs. Evening Turmeric Consumption on Urine Oxidative Stress Biomarkers in Obese, Middle-Aged Adults: A Feasibility Study.

The circadian rhythm of biological systems is an important consideration in developing health interventions. The immune and oxidative defense systems exhibit circadian periodicity, with an anticipatory increase in activity coincident with the onset of the active period. Spice consumption is associated with enhanced oxidative defense. The objective of this study was to test the feasibility of a protocol, comparing the effects of morning vs. evening consumption of turmeric on urine markers of oxidative stress in obese, middle-aged adults. Using a within-sample design, participants received each of four clock time x treatment administrations, each separated by one week: morning turmeric; evening turmeric; morning control; evening control. Participants prepared for each lab visit by consuming a low-antioxidant diet for two days and fasting for 12 h. Urine was collected in the lab at baseline and one-hour post-meal and at home for the following five hours. The results showed that the processes were successful in executing the protocol and collecting the measurements and that participants understood and adhered to the instructions. The findings also revealed that the spice treatment did not elicit the expected antioxidant effect and that the six-hour post-treatment urine collection period did not detect differences in urine endpoints across treatments. This feasibility study revealed that modifications to the spice treatment and urine sampling timeline are needed before implementing a larger study.

Evaluation of the Association of Perioperative UGT1A1 Genotype-Dosed gFOLFIRINOX With Margin-Negative Resection Rates and Pathologic Response Grades Among Patients With Locally Advanced Gastroesophageal Adenocarcinoma: A Phase 2 Clinical Trial.

Importance: Patients with locally advanced gastroesophageal adenocarcinoma (ie, stage ≥T3 and/or node positive) have high rates of recurrence despite surgery and adjunctive perioperative therapies, which also have high toxicity profiles. Evaluation of pharmacogenomically dosed perioperative gFOLFIRINOX (fluorouracil, leucovorin, oxaliplatin, and UGT1A1 genotype-directed irinotecan) to optimize efficacy while limiting toxic effects may have value. Objective: To evaluate the coprimary end points of margin-negative (R0) resection rates and pathologic response grades (PRGs) of gFOLFIRINOX therapy among patients with locally advanced gastroesophageal adenocarcinoma. Design, Setting, and Participants: This single-group phase 2 trial, conducted at 2 academic medical centers from February 2014 to March 2019, enrolled 36 evaluable patients with locally advanced adenocarcinoma of the esophagus, gastroesophageal junction, and gastric body. Data analysis was conducted in May 2019. Interventions: Patients received biweekly gFOLFIRINOX (fluorouracil, 2400 mg/m2 over 46 hours; oxaliplatin, 85 mg/m2; irinotecan, 180 mg/m2 for UGT1A1 genotype 6/6, 135 mg/m2 for UGT1A1 genotype 6/7, or 90 mg/m2 for UGT1A1 genotype 7/7; and prophylactic peg-filgastrim, 6 mg) for 4 cycles before and after surgery. Patients with tumors positive for ERBB2 also received trastuzumab (6-mg/kg loading dose, then 4 mg/kg). Main Outcomes and Measures: Margin-negative resection rate and PRG. Results: A total of 36 evaluable patients (27 [78%] men; median [range] age, 66 [27-85] years; 10 [28%] with gastric body cancer; 24 [67%] with intestinal-type tumors; 6 [17%] with ERBB2-positive tumors; 19 [53%] with UGT1A1 genotype 6/6; 16 [44%] with genotype 6/7; and 1 [3%] with genotype 7/7) were enrolled. Of these, 35 (97%) underwent surgery; 1 patient (3%) died after completing neoadjuvant chemotherapy while awaiting surgery. Overall, R0 resection was achieved in 33 of 36 patients (92%); 2 patients (6%) with linitis plastica achieved R1 resection. Pathologic response grades 1, 2, and 3 occurred in 13 patients (36%), 9 patients (25%), and 14 patients (39%), respectively, and PRG 1 was observed in 11 of 24 intestinal-type tumors (46%). Median disease-free survival was 30.1 months (95% CI, 15.0 months to not reached), and median overall survival was not reached (95% CI, 8.3 months to not reached). There were no differences in outcomes by UGT1A1 genotype group. A total of 38 patients, including 2 (5%) with antral tumors, were evaluable for toxic effects. Grade 3 or higher adverse events occurring in 5% or more of patients during the perioperative cycles included diarrhea (7 patients [18%]; 3 of 19 patients [16%] with genotype 6/6; 2 of 16 patients [13%] with genotype 6/7; 2 of 3 patients [67%] with genotype 7/7), anemia (2 patients [5%]), vomiting (2 patients [5%]), and nausea (2 patients [5%]). Conclusions and Relevance: In this study, perioperative pharmacogenomically dosed gFOLFIRINOX was feasible, providing downstaging with PRG 1 in more than one-third of patients and an R0 resection rate in 92% of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02366819.