Citations

AbstractBackgroundThe classic clinical picture of gastroparesis is a symptomatic patient losing weight. In addition, a number of patients with delayed gastric emptying are obese and/or gaining weight. Our aim was to investigate the factors impacting body weight in patients with idiopathic gastroparesis.MethodsIn patients with idiopathic gastroparesis, detailed history and weight were acquired at enrollment and after 48 weeks. Questionnaires assessed symptoms, food intake, physical activity, and quality of life. Patients underwent laboratory testing, gastric emptying scintigraphy, and water load testing.ResultsOf 138 patients with idiopathic gastroparesis, 10% were underweight (BMI < 18.5), 39% were normal weight (BMI 18.5‐25), 20% were overweight with BMI 25 to 30 kg/m2, and 29% were obese with BMI > 30 kg/m2. Body weight at enrollment was positively associated with oral caloric consumption (P < .001), following a gastroparesis diet (P = .04), nutrition consultation (P = .001), upper abdominal pain (P = .01); and negatively associated with energy expenditure (P = .05), alcohol use (P = .003) and severity of bloating (P < .001). When followed over 48 weeks, 53% patients stayed stable (within 5% of baseline weight), 30% gained, and 17% lost weight. Weight gain over 48 weeks was positively associated with oral caloric consumption (P = .003) and constipation severity (P = .005) at enrollment, and negatively associated with lower abdominal pain severity (P = .007) at enrollment, and associated with improvement in inability to finish meal score (P < .001) at 48 weeks.ConclusionsIn this series of patients with idiopathic gastroparesis, 10% were underweight whereas 29% were obese. Over 48 weeks, 30% of patients increased their body weight ≥ 5%. Diet, activity, and symptoms are important factors associated with body weight in patients with idiopathic gastroparesis.

Abstract Objective. —To assemble and interpret karyotype data provided as part of the College of American Pathologists/American College of Medical Genetics Cytogenetics Proficiency Testing Program. Data Sources, Extraction, and Synthesis. —The Cytogenetics Resource Committee requested data on all cells analyzed in a 1994 whole-blood specimen challenge. In that study, 287 participating laboratories analyzed a total of 14297 cells derived from a sample drawn from an adult donor with Turner syndrome. This individual had previously been found to have mosaicism, including cell lines with X structural anomalies along with monosomy X, making this an excellent challenge for a multicenter cytogenetic survey. Results and Conclusions. —Analysis of the data from this extensive study revealed mosaicism of up to 10 different sex chromosome complements involving the X chromosome with and without a small ring X or a derivative X chromosome. In the routine cytogenetic analysis performed by the participating laboratories, cell lines observed, in decreasing order of prevalence, included 45,X (n = 8357 cells), 46,X,r(X) (n = 3597), 46,X,der( X )t( X ;X) (n = 2237), 46,XX (n = 93), 47,X,r(X),r(X) (n = 5), 47,X,der( X )t( X ;X),der( X )t( X ;X) (n = 3), 47,XX,r(X) (n = 2), and one observation each of 47,XX,der( X )t( X ;X), 47,X,der( X )t( X ;X),r(X), and 47,XXX. Our molecular cytogenetic data, as well as detailed analysis of G-banded chromosomes, suggest the nomenclature for these 2 abnormal X chromosomes as r(X)(p11.3q21.3) and der( X )t( X ;X)(p11.3;q21.3), and we discuss models for the concomitant formation of these 2 entities. Both the degree of analysis and the extensive mosaicism that was discovered in this study are exceptional, and similar reported cases as well as possible mechanisms for the observed X chromosome instability are reviewed.

AbstractBackgroundUnderstanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management. Aims: (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL.MethodsGastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI‐SYM and Rome III), QOL (SF‐36v2 and PAGI‐QOL), depression (Beck Depression Inventory [BDI]), and anxiety (State Trait Anxiety InventoryAQ7).Key Results715 gastroparesis patients (256 diabetic (DG), 459 idiopathic (IG)) were evaluated. SF‐36 physical component (PC) score averaged 33.3 ± 10.5; 41% had impaired score <30. SF‐36 PC scores were similar between diabetic and idiopathic gastroparesis. Impaired SF‐36 PC associated with increased nausea/vomiting and upper abdominal pain subscores, acute onset of symptoms, higher number of comorbidities, use of narcotic pain medications, and irritable bowel syndrome (IBS). SF‐36 mental component (MC) score averaged 38.9 ± 13.0; 26% had impaired score <30. Poor SF‐36 MC associated with diabetic etiology, higher Beck depression inventory, and state anxiety scores. PAGI‐QOL score averaged 2.6 ± 1.1; 50% had a score of <2.6. Low PAGI‐QOL associated with higher fullness, bloating, and upper abdominal pain subscores, more depression and Trait anxiety, smoking cigarettes, need for nutritional support, progressively worsening symptoms and periodic exacerbations.Conclusions & InferencesMultiple measures show poor QOL present in gastroparesis. Several areas impacted on reduced QOL: (a) Symptoms of nausea, vomiting, and abdominal pain, as well as IBS; (b) Etiology and acute onset and progressively worsening symptoms; (c) Comorbidities and psychological factors such as anxiety and depression; (d) Patient‐related factors such as smoking. Targeting the modifiable factors may improve patient outcomes in gastroparesis.

320 Background: Genomic profiling studies have reported somatic HER2 mutations in ~2–5% of biliary tract cancers (BTC). Clinical data from the SUMMIT study demonstrate that neratinib, a pan-HER irreversible tyrosine kinase inhibitor, has encouraging clinical activity in multiple types of HER2-mutant solid tumor malignancies. Methods: SUMMIT is a multi-histology, open-label, phase II ‘basket’ study of neratinib in patients with somatic HER2 mutations (ClinicalTrials.gov NCT01953926). Patients with activating somatic HER2 mutations with different histologies, including BTC, received neratinib monotherapy (240 mg oral daily). Loperamide prophylaxis was mandatory during cycle 1. Efficacy endpoints: objective response rate (ORR, RECIST v1.1); clinical benefit rate (CBR); duration of response; progression-free survival (PFS). Adverse events (AEs) were assessed by CTCAE v4.0. Genomic profiling from fresh/archival tumor tissues and/or plasma cfDNA was performed retrospectively by next-generation sequencing (MSK-IMPACT). Results: As of 3-Sep-2020, 25 patients with HER2-mutant BTC were enrolled: gallbladder (40%); intrahepatic (24%); extrahepatic (20%); ampulla of Vater (16%). 68% of patients received ≥2 systemic regimens (96% received prior gemcitabine-based regimens). The S310F/Y variant accounted for nearly half of HER2 mutations (n=11). Other HER2 mutations: V777L (n=5); L755S (n=2); V842I (n=2); R678Q (n=2). Confirmed ORR in 25 evaluable patients was 12% (95% CI 3–31%) and CBR was 20% (95% CI 7–41%), including 3 confirmed PRs and 2 patients with SD for ≥16 weeks. Tumor shrinkage was observed in multiple HER2-activating mutations and enriched in gallbladder and extrahepatic subtypes of BTC. Median PFS was 2.8 (95% CI 1.1–3.7) months; median overall survival (OS) was 5.4 (95% CI 3.7–11.7) months. Nine (36%) patients (3 of whom with ECOG PS 2) came off study within 28 (range 6–47) days of treatment due to clinical deterioration (unrelated to study drug) followed by death. The most common treatment-related AEs (any grade) were diarrhea (56%) and vomiting (48%). Diarrhea was the most common Grade 3 event (24%); 4 patients (16%) required a neratinib dose reduction; no patients discontinued treatment due to diarrhea. Conclusions: Neratinib is safe and tolerable in patients with advanced BTC patients and somatic HER2 mutations. The antitumor activity of neratinib appears comparable to current standards of care, with similar PFS and OS in heavily pretreated patients. Analysis of co-occurring oncogenic mutations and response is ongoing, and consideration is being given to neratinib-based combination regimens to further improve outcomes in this setting. Clinical trial information: NCT01953926.

Objective This study aims to determine if low iodine dynamic computed tomography angiography performed after a fixed delay or test bolus acquisition demonstrates high concordance with clinical computed tomography angiography (using a routine amount of iodinated contrast) to display lower extremity peripheral arterial disease. Methods After informed consent, low iodine dynamic computed tomography angiography examination (using either a fixed delay or test bolus) using 50 ml of iodine contrast media was performed. A subsequent clinical computed tomography angiography using standard iodine dose (115 or 145 ml) served as the reference standard. A vascular radiologist reviewed dynamic and clinical computed tomography angiography images to categorize the lumen into “not opacified”, “<50% stenosis”, “ 50 ̶70% stenosis”, “>70% stenosis”, and “occluded” for seven arterial segments in each lower extremity. Concordance between low iodine dynamic computed tomography angiography and the routine iodine reference standard was calculated. The clinical utility of 4D volume-rendered images was also evaluated. Results Sixty-eight patients (average age 66.1 ± 12.3 years, male; female = 49: 19) were enrolled, with 34 patients each undergoing low iodine dynamic computed tomography angiography using fixed delay and test bolus techniques, respectively. One patient assigned to the test bolus group did not undergo low iodine computed tomography angiography due to unavailable delayed time. The fixed delay was 13 s, with test bolus acquisition resulting in a mean variable delay prior to image acquisition of 19.5 s (range; 8–32 s). Run-off to the ankle was observed using low iodine dynamic computed tomography angiography following fixed delay and test bolus acquisition in 76.4% (26/34) and 100% (33/33) of patients, respectively ( p = 0.005). Considering extremities with run-off to the ankle and without severe artifact, the concordance rate between low iodine dynamic computed tomography angiography and the routine iodine reference standard was 86.8% (310/357) using fixed delay and 97.9% (425/434) using test bolus ( p < 0.001). 4D volume-rendered images using fixed delay and test bolus demonstrated asymmetric flow in 57.7% (15/26) and 58.1% (18/31) ( p = 0.978) of patients, and collateral blood flow in 11.5% (3/26) and 22.6% (7/31) of patients ( p = 0.319), respectively. Conclusion Low iodine dynamic computed tomography angiography with test bolus acquisition has a high concordance with routine peripheral computed tomography angiography performed with standard iodine dose, resulting in improved run-off to the ankle compared to dynamic computed tomography angiography performed after a fixed delay. This method is useful for minimizing iodine dose in patients at risk for contrast-induced nephropathy. 4D volume-rendered computed tomography angiography images provide useful dynamic information.

Abstract Background Recent findings indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the cerebrospinal fluid (CSF) correlates of SARS-CoV-2 encephalitis. Methods Patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC), and healthy controls (HC) underwent an extended panel of CSF neuronal (neurofilament light chain [NfL], T-tau), glial (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], chitinase-3-like protein 1 [YKL-40]) and inflammatory biomarkers (interleukin [IL]-1β, IL-6, Il-8, tumor necrosis factor [TNF] α, CXCL-13, and β2-microglobulin). Results Thirteen COV-Enc, 21 ENC, and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and β2-microglobulin and glial markers (GFAP, sTREM2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-tau were abnormal only in severe cases. Conclusions SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2-related encephalitis.

Introduction Latino populations, particularly those living in rural areas, experience a disproportionately high prevalence and poorer outcomes of type 2 diabetes mellitus (T2DM). The purpose of this study was to test the acceptability and perceived effectiveness of a group-based, facilitated digital storytelling intervention for T2DM self-management among rural Latino patients. Method Twenty Latino adults with T2DM participated in facilitated storytelling discussions at two primary clinics. Participants viewed a 12-minute T2DM self-management digital storytelling intervention, followed by a facilitated group discussion. Surveys, observations, and focus groups were used to assess for acceptability and perceived effectiveness of the intervention through descriptive and qualitative analysis, informed by narrative and social cognitive theory. Results All participants found the intervention interesting and useful and reported improvement in confidence, motivation, and behavioral intentions for T2DM self-management. Themes mapped closely with narrative theory models, further suggestive of the behavior change potential. Discussion Facilitated discussions may add value to viewing of digital stories and represent a scalable approach to provide culturally congruent health care for Latino patients with diabetes in rural settings. Within the paradigm of group-based diabetes educational programs, this lends itself well to critical transcultural nursing care.