Utilization and impact of esophageal string testing in children with eosinophilic esophagitis: A 1 year experience.

The 1-h esophageal string test (EST) is a minimally invasive test that can be used to monitor eosinophilic esophagitis (EoE) disease activity and guide treatment without endoscopy. We aimed to describe the real-world utilization and impact of EST on the care of children with EoE over the first year this was used at our center. Between 12/1/2022 and 11/30/2023, 39 ESTs were successful in 45 attempts (87% completion rate) in 31 patients. Five patients underwent multiple ESTs. Adverse events during the EST included vomiting. Reasons for failure to complete the EST (13%, n = 6) were patients could not swallow the capsule (n = 5) and vomiting (n = 1). EST was used to assess EoE without the need for endoscopy in 95% (n = 37) of cases. Treatment approach varied based on whether the EST indicated active (38.5%) or inactive (61.5%) EoE. The EST is a well-tolerated minimally invasive disease monitoring tool for patients with EoE.

Transnasal endoscopy ease score "TNEase score" to evaluate patient tolerance of unsedated transnasal endoscopy.

Transnasal endoscopy (TNE) with virtual reality (VR) distraction allows for unsedated pediatric upper endoscopy. Understanding the pediatric population that is successful with TNE is imperative for patient selection and experience. We developed a "TNEase Score" to assess patient tolerance from the physician's assessment. The aim of this study was to identify factors that influence patient's acceptance and tolerability of sedation-free TNE in pediatric patients undergoing the procedure. From March 2020 to April 2021, 110 TNEs were performed on subjects 5-22 years of age. The overall completion rate was 98.1%. Of these subjects, 66 subjects (60%) were graded by the gastroenterologist as TNEase Score 1 (with ease); 27 subjects (25%) were graded as TNEase Score 2 (minimal complaints); nine subjects (8%) were graded as TNEase score 3 (moderate complaints, required frequent reassurance); six subjects were graded as TNEase Score 4 (significant complaints and resistance); two subjects (2%) were graded as TNEase Score 5 (procedure terminated). Feasibility of TNE was significantly related to age, height, and whether the patient had undergone previous TNE. Thus, young age, shorter height, and first time TNE were significant predictors of higher TNEase score or difficulty tolerating TNE. Factors examined that did not predict higher TNEase score included gender, junior versus senior endoscopist, past medical history of anxiety, autism, attention-deficit/hyperactivity disorder (ADHD), or history of using a nasal spray at home. "TNEase score" allowed grading of the subject's experience and the majority of patients tolerated TNE with minimal complaints.

Assessment of the surface contamination of the primary packaging of oral antineoplastic drugs and secondary packaging of chemotherapy preparations at a Swiss hospital.

INTRODUCTION: Due to the high toxicity of antineoplastic drugs, handling their packaging could lead to the chemical contamination of hospital environments and exposure risks to healthcare professionals and patients. This study aimed to assess the contamination of two main surfaces: the outer primary packaging of oral antineoplastic drug formulations (n = 36) available on the Swiss market and the surface of secondary packaging of injectable antineoplastic drug preparations (n = 60) produced by the pharmacy of a Swiss hospital and carriers used for transport (n = 5). METHODS: Samples were collected using a validated wipe sampling method. The simultaneous analysis of 24 antineoplastic drugs: 5-fluorouracil, busulfan, carboplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine) and 1 antiviral compound (ganciclovir) was performed by UHPLC-MS/MS. RESULTS: A total of 58% and 90% positive results were obtained for the primary packaging of oral chemotherapies and for the secondary packaging of injectable preparations, respectively. The highest quantities found on the primary packaging for oral chemotherapies and on the surface of closed leak-proof bags were 111 ng of methotrexate and 19 ng of gemcitabine, respectively. Gemcitabine (69%) and cyclophosphamide (38%) were the two most common contaminants found on the packaging of injectable preparations and carriers, regardless of the chemotherapy preparations. CONCLUSION: Trace levels (ng) of antineoplastic drugs can be found on most surfaces of all evaluated pharmaceutical products. Thus, suitable personal protective equipment is mandatory for healthcare professional handling antineoplastic drugs.

One Year Into Dupilumab: Physician and Patient Experiences in Initiating Dupilumab for Pediatric Eosinophilic Esophagitis.

In 2022, the US Food and Drug Administration approved dupilumab for treatment of eosinophilic esophagitis (EoE). The aims of this study were to report physician and patient perspectives on initiating dupilumab. A 2-pronged approach was used: (1) data on physician prescribing practices was gathered via retrospective chart review of EoE patients prescribed dupilumab and (2) pediatric patients on dupilumab were approached to complete a questionnaire regarding reasons for initiation. During this time, 42 patients were prescribed dupilumab. From the physician's perspective, the primary reasons for dupilumab included nonresponse to topical corticosteroids (TCS) (52%), nonadherence (28%), adverse effects (10%), or to treat multiple atopic diseases (5%). The median dupilumab initiation time, from day prescribed to first injection, was 37 days [interquartile range (IQR) 37]. Almost all required prior authorization (PA) (98%), while 17% required letter of appeal and 2% required peer-to-peer. Fifteen patients (36%) completed the questionnaire portion of the study. From the patient's perspective, the primary reasons for dupilumab initiation included nonresponse to TCS (27%), nonadherence to TCS (27%), concern about adverse effects of TCS (7%), and treatment of multiple atopic diseases (33%). In conclusion, physicians are prescribing dupilumab primarily for nonresponse to TCS and almost all required PA with a long delay to starting dupilumab.

Trajectories and risk factors of fatigue following colorectal cancer diagnosis.

AIM: This study sought to identify groups of colorectal cancer patients based upon trajectories of fatigue and examine how demographic, clinical and behavioural risk factors differentiate these groups. METHOD: Patients were from six cancer centres in the United States and Germany. Fatigue was measured using the fatigue subscale of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) at five time points (baseline/enrolment and 3, 6, 12 and 24 months after diagnosis). Piecewise growth mixture models identified latent trajectories of fatigue. Logistic regression models examined differences in demographic, clinical and behavioural characteristics between fatigue trajectory groups. RESULTS: Among 1615 participants (57% men, 86% non-Hispanic White, mean age 61 ± 13 years at diagnosis), three distinct groups were identified. In the high fatigue group (36%), fatigue significantly increased in the first 6 months after diagnosis and then showed statistically and clinically significant improvement from 6 to 24 months (P values < 0.01). Throughout the study period, average fatigue met or exceeded cutoffs for clinical significance. In the moderate (34%) and low (30%) fatigue groups, fatigue levels remained below or near population norms across the study period. Patients who were diagnosed with Stage II-IV disease and/or current smokers were more likely to be in the high fatigue than in the moderate fatigue group (P values < 0.05). CONCLUSION: A large proportion of colorectal cancer patients experienced sustained fatigue after initiation of cancer treatment. Patients with high fatigue at the time of diagnosis may benefit from early supportive care.

Intravenous Infusion of the ß3-Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic Function in Dogs With Systolic Heart Failure.

BACKGROUND: Unlike ß1- and ß2-adrenergic receptors (ARs), ß3-AR stimulation inhibits cardiac contractility and relaxation. In the failing left ventricular (LV) myocardium, ß3-ARs are upregulated, and can be maladaptive in the setting of decompensation by contributing to LV dysfunction. This study examined the effects of intravenous infusions of the ß3-AR antagonist APD418 on cardiovascular function and safety in dogs with systolic heart failure (HF). METHODS AND RESULTS: Three separate studies were performed in 21 dogs with coronary microembolization-induced HF (LV ejection fraction [LVEF] of approximately 35%). Studies 1 and 2 (n = 7 dogs each) were APD418 dose escalation studies (dosing range, 0.35-15.00 mg/kg/h) designed to identify an effective dose of APD418 to be used in study 3. Study 3, the sustained efficacy study, (n = 7 dogs) was a 6-hour constant intravenous infusion of APD418 at a dose of 4.224 mg/kg (0.70 mg/kg/h) measuring key hemodynamic endpoints (e.g., EF, cardiac output, the time velocity integral of the mitral inflow velocity waveform representing early filling to time-velocity integral representing left atrial contraction [Ei/Ai]). Studies 1 and 2 showed a dose-dependent increase of LVEF and Ei/Ai, the latter being an index of LV diastolic function. In study 3, infusion of APD418 over 6 hours increased LVEF from 31 ± 1% to 38 ± 1% (P < .05) and increased Ei/Ai from 3.4 ± 0.4 to 4.9 ± 0.5 (P < .05). Vehicle had no effect on the LVEF or Ei/Ai. In study 3, APD418 had no significant effects on the HR or the systemic blood pressure. CONCLUSIONS: Intravenous infusions of APD418 in dogs with systolic HF elicit significant positive inotropic and lusitropic effects. These findings support the development of APD418 for the in-hospital treatment of patients with an acute exacerbation of chronic HF.

Symptomology following mRNA vaccination against SARS-CoV-2.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

Case Series: Role of Pill Esophagram to Identify Pediatric Patients With Eosinophilic Esophagitis Amenable to Therapeutic Dilation.

Eosinophilic esophagitis (EoE) is a chronic disease of the esophagus that leads to esophageal remodeling. Dysphagia is a common symptom that likely results from the inflammatory process or remodeling. Identifying patients that may benefit from dilation can be challenging because of difficulties in detecting subtle narrowing in patients with EoE. Here we report the benefits of a pill esophagram in the detection of esophageal narrowing in EoE. We identified a series of children with EoE and symptoms of dysphagia who underwent barium esophagram with a barium-coated pill to assess symptoms. Three subjects had a normal fluoroscopic esophagram but had pill retention for greater than 5 minutes. Subsequent esophagoscopy and esophageal dilation revealed mucosal rent after dilation. Subtle esophageal narrowing may not be captured with barium esophagram alone in children with EoE and dysphagia. Use of the barium pill in symptomatic patients can assist in identifying patients who may benefit from esophageal dilation.

Transnasal Endoscopy in Unsedated Children With Eosinophilic Esophagitis Using Virtual Reality Video Goggles.

BACKGROUND & AIMS: Evaluation and treatment of children with eosinophilic esophagitis (EoE) requires serial endoscopic, visual, and histologic assessment by sedated esophagogastroduodenoscopy (EGD). Unsedated transnasal endoscopy (TNE) was reported to be successful in a pilot study of children. We evaluated video goggle and virtual reality-based unsedated TNE in children with EoE, collecting data on rates of completion, adverse events, and adequacy of visual and histologic findings. METHODS: We performed a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE from January 2015 through February 2018. We analyzed data on patient demographics, procedure completion, endoscope type, adverse events, visual and histologic findings, estimated costs, and duration in the facility. Esophageal biopsies from the first 173 subjects who underwent TNE were compared with those from previous EGD evaluations. RESULTS: During 300 attempts, 294 TNEs were performed (98% rate of success). Fifty-four patients (age, 6-18 y) underwent multiple TNEs for dietary or medical management of EoE. There were no significant adverse events. Visual and histologic findings were adequate for assessment of EoE. TNE reduced costs by 53.4% compared with EGD (TNE $4393.00 vs EGD $9444.33). TNE was used increasingly from 2015 through 2017, comprising 31.8% of endoscopies performed for EoE. The total time spent in the clinic (front desk check-in to check-out) in 2018 was 71 minutes. CONCLUSIONS: In a retrospective study of 190 children and young adults (age, 3-22 y) who underwent video goggle or virtual reality-based unsedated TNE, TNE was safe and effective and reduced costs of EoE monitoring. Advantages of TNE include reduced risk and cost associated with anesthesia as well as decreased in-office time, which is of particular relevance for patients with EoE, who require serial EGDs.

Short Telomeres Induce p53 and Autophagy and Modulate Age-Associated Changes in Cardiac Progenitor Cell Fate.

Aging severely limits myocardial repair and regeneration. Delineating the impact of age-associated factors such as short telomeres is critical to enhance the regenerative potential of cardiac progenitor cells (CPCs). We hypothesized that short telomeres activate p53 and induce autophagy to elicit the age-associated change in CPC fate. We isolated CPCs and compared mouse strains with different telomere lengths for phenotypic characteristics of aging. Wild mouse strain Mus musculus castaneus (CAST) possessing short telomeres exhibits early cardiac aging with cardiac dysfunction, hypertrophy, fibrosis, and senescence, as compared with common lab strains FVB and C57 bearing longer telomeres. CAST CPCs with short telomeres demonstrate altered cell fate as characterized by cell cycle arrest, senescence, basal commitment, and loss of quiescence. Elongation of telomeres using a modified mRNA for telomerase restores youthful properties to CAST CPCs. Short telomeres induce autophagy in CPCs, a catabolic protein degradation process, as evidenced by reduced p62 and increased accumulation of autophagic puncta. Pharmacological inhibition of autophagosome formation reverses the cell fate to a more youthful phenotype. Mechanistically, cell fate changes induced by short telomeres are partially p53 dependent, as p53 inhibition rescues senescence and commitment observed in CAST CPCs, coincident with attenuation of autophagy. In conclusion, short telomeres activate p53 and autophagy to tip the equilibrium away from quiescence and proliferation toward differentiation and senescence, leading to exhaustion of CPCs. This study provides the mechanistic basis underlying age-associated cell fate changes that will enable identification of molecular strategies to prevent senescence of CPCs. Stem Cells 2018;36:868-880.

Epithelial Claudin Proteins and Their Role in Gastrointestinal Diseases.

Our bodies are protected from the external environment by mucosal barriers that are lined by epithelial cells. The epithelium plays a critical role as a highly dynamic, selective semipermeable barrier that separates luminal contents and pathogens from the rest of the body and controlling the absorption of nutrients, fluid and solutes. A series of protein complexes including the adherens junction, desmosomes, and tight junctions function as the principal barrier in paracellular diffusion and regulators of intracellular solute, protein, and lipid transport. Tight junctions are composed of a series of proteins called occludins, junctional adhesion molecules, and claudins that reside primarily as the most apical intercellular junction. Here we will review one of these protein families, claudins, and their relevance to gastrointestinal and liver diseases.

Unsedated In-office Transgastrostomy Esophagoscopy to Monitor Therapy in Pediatric Esophageal Disease.

Monitoring therapy in esophageal inflammatory disorders such as eosinophilic esophagitis and reflux esophagitis often requires frequent endoscopic evaluation. We recently reported the effective use of unsedated in-office transnasal esophagoscopy that significantly decreased costs and anesthetic exposure associated with pediatric esophagoscopy in eosinophilic esophagitis. Here we report a series of pediatric patients with esophagitis with gastrostomy tubes who underwent unsedated transgastrostomy esophagoscopy (TGE) in an office setting. Nine patients (ages 16 months-21 years) tolerated TGE without significant adverse events. Biopsy specimens were adequate for evaluation. This series confirms that unsedated in-office TGE can be used to successfully obtain mucosal biopsies to monitor esophageal inflammatory conditions in children without the use of sedation.

Mindfulness practice reduces cortisol blunting during chemotherapy: A randomized controlled study of colorectal cancer patients.

BACKGROUND: The objective of this randomized clinical experiment was to test the influence of a mindfulness meditation practice, when delivered during 1 session of active chemotherapy administration, on the acute salivary cortisol response as a marker of neuroendocrine system activity in cancer patients. METHODS: A mindfulness, attention-control, or resting exposure was assigned to 57 English- or Spanish-speaking colorectal cancer patients at 1 county oncology clinic and 1 university oncology clinic at the start of chemotherapy. Saliva samples were collected at the start of chemotherapy and at subsequent 20-minute intervals during the first 60 minutes of chemotherapy (4 samples in all). Self-reporting on biobehavioral assessments after chemotherapy included distress, fatigue, and mindfulness. RESULTS: An area-under-the-curve analysis (AUC) showed a relative increase in cortisol reactivity in the mindfulness group after adjustments for biological and clinical measures (ß = 123.21; P = .03). More than twice as many patients in the mindfulness group versus the controls displayed a cortisol rise from the baseline to 20 minutes (69% vs 34%; P = .02). AUC values were uncorrelated with biobehavioral measure scores, although mindfulness scores were inversely correlated with fatigue (r = -0.46; P < .01) and distress scores (r = -0.54; P < .01). CONCLUSIONS: Findings suggest that mindfulness practice during chemotherapy can reduce the blunting of neuroendocrine profiles typically observed in cancer patients. Implications include support for the use of mindfulness practice in integrative oncology. Cancer 2017;123:3088-96. © 2017 American Cancer Society.

DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

BACKGROUND: The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. METHODS: A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. RESULTS: The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. CONCLUSIONS: The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of individuals with dMMR tumors were confirmed to have Lynch syndrome. Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2017;123:3732-3743. © 2017 American Cancer Society.

Shared health characteristics in Hispanic colorectal cancer patients and their primary social support person following primary diagnosis.

PURPOSE: The aim of this paper was to determine individual and shared levels of psychosocial, behavioral, and symptomological health characteristics among Hispanics with recent history of cancer and their primary social support person (PSSP) in the years following diagnosis. PATIENTS AND METHODS: Recruited from a population-based cohort study were 409 Hispanic patients with a previous diagnosis of colorectal cancer. Forty-seven patients identified a PSSP, who assists with medical decision-making and health-related matters, who also participated in the study. Current behavioral (smoking, alcohol use, physical activity, and complementary and alternative medicine use), psychosocial (stress and mindfulness), and physical symptom (fatigue) data were obtained using validated instruments. Analyses tested the individual and shared (between patients and PSSPs) variance in these health measures. RESULTS: The sample was diagnosed on average 3.1 years (standard deviation = 1.7) prior to assessment. PSSPs were mainly spouses/partners (63%) or children (28%) of patients. Among patients, stress was positively associated with being a current smoker (p < 0.01) and with fatigue (r = 0.45, p < 0.001); stress was negatively correlated with mindfulness (r = -0.41, p < 0.001); mindfulness was negatively associated with smoking (odds ratio (OR) = 0.72, p < 0.01) and alcohol consumption (OR = 0.83, p < 0.05); the inverse relationship between mindfulness and fatigue was partially mediated through lower levels of stress (ß = -0.17, p < 0.001). Similar patterns were observed among PSSPs. Patient mindfulness was negatively correlated with PSSP stress (r = -0.45, p < 0.01). Complementary and alternative medicine use showed interdependence between patients and PSSPs for use of herbal remedies (OR = 6.2; p < 0.01) and bodywork (OR = 8.3, p < 0.05). CONCLUSION: Hispanic colorectal cancer patients and their PSSP share a common health milieu in the years following a cancer diagnosis, offering opportunities for advancing interpersonal intervention approaches in cancer care. Copyright © 2015 John Wiley & Sons, Ltd.

Rejuvenating the senescent heart.

PURPOSE OF REVIEW: The purpose of this review is to provide an update on the cardiac stem cell field with an emphasis on aging and to suggest some relevant strategies directed toward rejuvenation of the senescent heart. RECENT FINDINGS: Stem cells were long considered as a fountain of youth and were assumed to be equipped against any form of aging effect. However, it is now clear that stem cells suffer the consequences of aging as well. With the discovery that cardiac stem cells reside in the heart comes the question whether these cells are also impaired upon aging. As cardiac stem cell properties are also altered with age, autologous stem cell-based therapy to treat heart failure will benefit from new improved strategies. SUMMARY: With the goal to improve stem cell properties that are impaired upon aging, some strategies are highlighted. Genetic modification of adult human cardiac progenitor cells prior to autologous stem cell-based therapy, delivery of the next generation of stem cells such as CardioChimeras and CardioClusters, and improvement of the myocardial environment with rejuvenating factors constitute some of the possibilities and are discussed in more detail in this review.