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.

Sedation-free transnasal esophagoscopy to evaluate and monitor esophageal diseases in children with esophageal atresia-tracheoesophageal fistula.

Patients with esophageal atresia and tracheoesophageal fistula (EA-TEF) are at increased risk of conditions including gastroesophageal reflux, peptic esophagitis, gastric metaplasia, anastomotic strictures, eosinophilic esophagitis, and dysphagia. Patients with TEF-EA may need serial endoscopy in their lifetime given the known short- and long-term GI complications. There has been increased interest in pediatric unsedated transnasal endoscopy (TNE) as an endoscopic alternative as it is lower cost, has shorter recovery time, and eliminates potential risks associated with anesthesia. We report on the use of TNE with EA-TEF in four patients: One patient had gastroesophageal reflux disease, one patient had eosinophilic esophagitis and TNE was used for surveillance in two patients. Use of TNE allowed for close endoscopic monitoring and changes in medication management. The third and fourth patients underwent TNE as part of routine EA-TEF screening which is recommended by societal guidelines (Krishnan et al, J Pediatr Gastroenterol Nutr. 2016;63(5):550-570). Unsedated TNE is an alternative endoscopic approach in the management of patients with EA-TEF.

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.

Clinical Evaluation of the Child with Eosinophilic Esophagitis.

The diagnosis of eosinophilic esophagitis (EoE) is based on clinical symptoms of esophageal dysfunction and eosinophil predominant esophageal inflammation. Clinical symptoms in children with EoE vary based on age and may be nonspecific. EoE has a male predominance with the majority having comorbid atopic disorders. At present, treatment options include medications (proton pump inhibition, swallowed topical steroids), dietary therapy or biologic therapy (dupilumab, approved for those ≥12 years of age). Outside of EoE in the context of oral immunotherapy, EoE is typically chronic requiring lifelong therapy. Long-term complications including feeding difficulties, malnutrition, and fibrostenotic disease.

Spectrum of somatic mutational features of colorectal tumors in ancestrally diverse populations.

Ancestrally diverse and admixed populations, including the Hispanic/Latino/a/x/e community, are underrepresented in cancer genetic and genomic studies. Leveraging the Latino Colorectal Cancer Consortium, we analyzed whole exome sequencing data on tumor/normal pairs from 718 individuals with colorectal cancer (128 Latino, 469 non-Latino) to map somatic mutational features by ethnicity and genetic ancestry. Global proportions of African, East Asian, European, and Native American ancestries were estimated using ADMIXTURE. Associations between global genetic ancestry and somatic mutational features across genes were examined using logistic regression. TP53 , APC , and KRAS were the most recurrently mutated genes. Compared to non-Latino individuals, tumors from Latino individuals had fewer KRAS (OR=0.64, 95%CI=0.41-0.97, p=0.037) and PIK3CA mutations (OR=0.55, 95%CI=0.31-0.98, p=0.043). Genetic ancestry was associated with presence of somatic mutations in 39 genes (FDR-adjusted LRT p<0.05). Among these genes, a 10% increase in African ancestry was associated with significantly higher odds of mutation in KNCN (OR=1.34, 95%CI=1.09-1.66, p=5.74×10 -3 ) and TMEM184B (OR=1.53, 95%CI=1.10-2.12, p=0.011). Among RMGs, we found evidence of association between genetic ancestry and mutation status in CDC27 (LRT p=0.0084) and between SMAD2 mutation status and AFR ancestry (OR=1.14, 95%CI=1.00-1.30, p=0.046). Ancestry was not associated with tumor mutational burden. Individuals with above-average Native American ancestry had a lower frequency of microsatellite instable (MSI-H) vs microsatellite stable tumors (OR=0.45, 95%CI=0.21-0.99, p=0.048). Our findings provide new knowledge about the relationship between ancestral haplotypes and somatic mutational profiles that may be useful in developing precision medicine approaches and provide additional insight into genomic contributions to cancer disparities. Significance: Our data in ancestrally diverse populations adds essential information to characterize mutational features in the colorectal cancer genome. These results will help enhance equity in the development of precision medicine strategies.

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.

Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T-cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92·3% of patients received the primer vaccine, 70·8% received one monovalent booster, but only 30·1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR=0·61, P=0·024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed. Highlights: COVID-19 booster vaccinations increase antibody levels and maintain T-cell responses against SARS-CoV-2 in patients receiving various anti-cancer therapiesBooster vaccinations reduced all-cause mortality in patientsA significant proportion of patients remain unboosted and strategies are needed to encourage patients to be up-to-date with vaccinations.

A case of food and aeroallergen sublingual immunotherapy inducing eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) has been reported secondary to aeroallergen sublingual immunotherapy (SLIT) and food allergen oral immunotherapy. Gastrointestinal symptoms with food allergen SLIT are uncommon, with no prior reports of cases of food allergen SLIT inducing EoE. Here we report a patient who developed EoE secondary to food and aeroallergen SLIT therapy that resolved with SLIT cessation.

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.

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.

Prophylactic inhaled corticosteroids for the management of recurrent croup.

OBJECTIVES: Croup is characterized by a barky cough, inspiratory stridor, hoarseness and varying degrees of respiratory distress. Acute croup episodes are often treated with oral, inhaled, or intravenous corticosteroids. Recurrent croup, defined as more than 2-3 episodes of acute croup in the same patient, can mimic asthma. We hypothesized that inhaled corticosteroids (ICS) given at the first sign of a respiratory viral prodrome can be a safe treatment to reduce the frequency of recurrent croup episodes in children without fixed airway lesions. METHODS: A retrospective chart review of patients being treated over an 18-month period was performed at a large tertiary care pediatric hospital following Institutional Review Board (IRB) approval. Patients under 21 years old referred to Pediatric Pulmonology, Otolaryngology, or Gastroenterology for recurrent croup were analyzed for their demographics, medical history, evaluation, treatment and clinical improvement. A Fisher's two-tailed exact test was used to compare the number of croup episodes before and after interventions. RESULTS: 124 patients were included in our analysis: 87 male and 34 female with a mean age of 54 months. Of these, 78 had >5 episodes of croup, 45 had 3-5, and 3 had 2 episodes prior to their first visit for recurrent croup. Operative direct laryngoscopy/bronchoscopy was performed in 35 patients (27.8%), with 60% showing a normal exam without fixed lesions. Ninety-two patients (74.2%) were treated with ICS, 24 were lost to follow up. Of the remaining 68 treated patients, 59 (86.7%) saw improvement with reduced severity and overall number of episodes of croup. Additionally, patients with >5 episodes of croup (47) as compared to <5 (12) were more likely to improve with ICS, (p = 0.003). There were no adverse reactions reported with ICS treatment. CONCLUSION: The novel initiation of ICS at the earliest sign of a viral upper respiratory infection shows promise as a safe preventative treatment to mitigate the frequency of recurrent croup episodes.

Pediatric Unsedated Transnasal Endoscopy.

Unsedated transnasal endoscopy (TNE) is a feasible, safe, and cost-effective procedure for pediatric patients. TNE provides direct visualization of the esophagus and enables acquisition of biopsy samples while eliminating the risks associated with sedation and anesthesia. TNE should be considered in the evaluation and monitoring of disorders of the upper gastrointestinal tract, particularly in diseases such as eosinophilic esophagitis that often require repeated endoscopy. Setting up a TNE program requires a thorough business plan as well as training of staff and endoscopists.

Investigation of liquid biopsy analytes in peripheral blood of individuals after SARS-CoV-2 infection.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) is linked to severe organ damage. The identification and stratification of at-risk SARS-CoV-2 infected individuals is vital to providing appropriate care. This exploratory study looks for a potential liquid biopsy signal for PACS using both manual and machine learning approaches. METHODS: Using a high definition single cell assay (HDSCA) workflow for liquid biopsy, we analysed 100 Post-COVID patients and 19 pre-pandemic normal donor (ND) controls. Within our patient cohort, 73 had received at least 1 dose of vaccination prior to SARS-CoV-2 infection. We stratified the COVID patients into 25 asymptomatic, 22 symptomatic COVID-19 but not suspected for PACS and 53 PACS suspected. All COVID-19 patients investigated in this study were diagnosed between April 2020 and January 2022 with a median 243 days (range 16-669) from diagnosis to their blood draw. We did a histopathological examination of rare events in the peripheral blood and used a machine learning model to evaluate predictors of PACS. FINDINGS: The manual classification found rare cellular and acellular events consistent with features of endothelial cells and platelet structures in the PACS-suspected cohort. The three categories encompassing the hypothesised events were observed at a significantly higher incidence in the PACS-suspected cohort compared to the ND (p-value < 0.05). The machine learning classifier performed well when separating the NDs from Post-COVID with an accuracy of 90.1%, but poorly when separating the patients suspected and not suspected of PACS with an accuracy of 58.7%. INTERPRETATION: Both the manual and the machine learning model found differences in the Post-COVID cohort and the NDs, suggesting the existence of a liquid biopsy signal after active SARS-CoV-2 infection. More research is needed to stratify PACS and its subsyndromes. FUNDING: This work was funded in whole or in part by Fulgent Genetics, Kathy and Richard Leventhal and Vassiliadis Research Fund. This work was also supported by the National Cancer InstituteU54CA260591.

Survival Associated With Consolidated Multidisciplinary Care in Head and Neck Cancer: A Retrospective Cohort Study.

OBJECTIVE: To compare survival among patients with head and neck cancer before and after implementing a weekly multidisciplinary clinic and case conference. METHODS: A retrospective cohort study with chart review was conducted of 3081 patients (1431 preimplementation, 1650 postimplementation) diagnosed with stage I-IVB tumors in the oral cavity, oropharynx, hypopharynx, nasopharynx, or larynx. Pre- and postimplementation differences in overall and disease-specific survival 1, 2, and 3 years after diagnosis were assessed with unadjusted Kaplan-Meier curves and multivariable Cox proportional hazard regression models adjusted for demographic characteristics, comorbidity burden, smoking status, tumor site and stage, p16 status for oropharyngeal squamous cell cancer, and initial treatment modality. RESULTS: Patients less commonly presented with oropharyngeal squamous cell cancer and advanced tumors (III-IVB) and received primary treatment with surgery alone or with adjuvant therapy preimplementation than postimplementation. Overall survival at 3 years was 77.1% and 79.9% (P = .07) and disease-specific survival was 84.9% and 87.5% (P = .05) among pre- and postimplementation patients, respectively. At 3 years, preimplementation patients had slightly poorer overall (hazard ratio, 1.20; 95% CI, 1.02-1.40) and disease-specific (hazard ratio, 1.26; 95% CI, 1.03-1.54) adjusted survival than postimplementation patients. In unadjusted and adjusted analyses, survival improvements were more pronounced among patients with advanced disease. DISCUSSION: A multidisciplinary clinic and case conference were associated with improved outcomes among patients with head and neck cancer, especially those with advanced tumors. IMPLICATIONS FOR PRACTICE: All patients with head and neck cancer should receive multidisciplinary team management, especially those with advanced tumors.

A guide on transnasal endoscopy: setting up a pediatric unsedated endoscopy program.

Background: Unsedated transnasal endoscopy is becoming an increasingly popular option for the evaluation of upper gastrointestinal tract disorders in adults and children worldwide. This innovative technology has transformative potential as it provides for a more efficient, safe, and cost-effective method for endoscopy and reduces the risks associated with anesthesia, which is particularly relevant in pediatrics as endoscopy is commonly done under general anesthesia or conscious sedation. The aim is to address knowledge gaps amongst pediatric gastroenterologists who may be considering the development of a TNE program, detailing how to implement sedation-free TNE into practice for pediatric patients and current and forthcoming technologies. Methods: We conducted a comprehensive review of current literature and collection of data from experts and clinicians in the field on how sedation-free programs were started and being conducted. We aimed to collate the data to provide a guide to address knowledge gaps with a focus on setting up and starting a sedation-free endoscopy program. Results: Here in, we provide a detailed guide for implementing a sedation-free endoscopy program in pediatrics including design and layout of a TNE unit, special staffing needs, equipment, current and forthcoming technologies, financial considerations and training considerations. We highlight special considerations that are relevant in pediatrics incorporating distraction or dissociation techniques such as Virtual Reality Systems, developmentally appropriate preparation for children, and topical analgesia. Conclusion: Sedation-free endoscopy is a rapidly growing option for pediatric patients. Development of an unsedated pediatric endoscopy program will improve patient care, decrease the need for anesthesia, provide a lower cost and safe alternative to traditional sedated endoscopy, and is a viable component to a pediatric gastroenterology practice.

Longitudinal SARS-CoV-2 mRNA Vaccine-Induced Humoral Immune Responses in Patients with Cancer.

Longitudinal studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in patients with cancer are needed to optimize clinical care. In a prospective cohort study of 366 (291 vaccinated) patients, we measured antibody levels [anti-spike (IgG-(S-RBD) and anti-nucleocapsid immunoglobulin] at three time points. Antibody level trajectories and frequency of breakthrough infections were evaluated by tumor type and timing of treatment relative to vaccination. IgG-(S-RBD) at peak response (median = 42 days after dose 2) was higher (P = 0.002) and remained higher after 4 to 6 months (P = 0.003) in patients receiving mRNA-1273 compared with BNT162b2. Patients with solid tumors attained higher peak levels (P = 0.001) and sustained levels after 4 to 6 months (P < 0.001) compared with those with hematologic malignancies. B-cell targeted treatment reduced peak (P = 0.001) and sustained antibody responses (P = 0.003). Solid tumor patients receiving immune checkpoint inhibitors before vaccination had lower sustained antibody levels than those who received treatment after vaccination (P = 0.043). Two (0.69%) vaccinated and one (1.9%) unvaccinated patient had severe COVID-19 illness during follow-up. Our study shows variation in sustained antibody responses across cancer populations receiving various therapeutic modalities, with important implications for vaccine booster timing and patient selection. SIGNIFICANCE: Long-term studies of immunogenicity of SARS-CoV-2 vaccines in patients with cancer are needed to inform evidence-based guidelines for booster vaccinations and to tailor sequence and timing of vaccinations to elicit improved humoral responses.