Citations

History A 65-year-old male patient with a history of sarcomatoid renal cell carcinoma and prior right nephrectomy developed recurrent disease adjacent to the inferior vena cava. The patient underwent surveillance imaging 7 months after initiation of treatment with maximum-dose pazopanib and less than 1 month after completing a 2-month regimen of palliative stereotactic body radiation therapy to the right nephrectomy bed and site of recurrence. (Stereotactic body radiation therapy was initiated 5 months after pazopanib treatment was initiated.) One month after initiating treatment with pazopanib and 6 months before the surveillance imaging, the patient developed diarrhea and required ongoing treatment with loperamide to control symptoms. He denied any fatigue, mouth sores, or extremity pain, but described some abdominal pain and discomfort associated with the diarrhea. He was not experiencing any fevers, and vital signs were normal. White blood cell count was normal at 5100/μL (5.1 ×109/L) (reference range, 4200–10 200/μL [4.2–10.2 ×109/L]), with all components of the differential count also being normal. A normal serum albumin level of 3.9 g/dL (39 g/L) (reference range, 3.5–5.0 g/dL [35–50 g/L]) and low serum total protein level of 6.1 g/dL (61 g/L) (reference range, 6.3–7.9 g/dL [63–79 g/L]) were noted. A comprehensive metabolic panel was performed, indicating a serum chloride level of 98 mmol/L (reference range, 100–108 mmol/L) and an alkaline phosphatase level of 121 U/L (2.02 μkat/L) (reference range, 45–115 U/L [0.75–1.92 μkat/L]). The patient underwent surveillance imaging with contrast-enhanced CT of the abdomen and pelvis in the venous phase.

Abstract Former American football players are at risk for developing traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). The objective of this study was to determine whether hyposmia is present in traumatic encephalopathy syndrome. The study included 119 former professional American football players, 60 former college football players, and 58 same-age asymptomatic unexposed men from the DIAGNOSE CTE Research Project. All subjects included in the analysis had completed the Brief Smell Identification Test (B-SIT). Traumatic encephalopathy syndrome and the level of CTE certainty were diagnosed using the 2021 NINDS consensus diagnostic criteria. TES is categorized antemortem by provisional levels of increasing CTE certainty: Suggestive, Possible, and Probable. Former players who had traumatic encephalopathy syndrome and Probable CTE had lower B-SIT scores than those with TES and Suggestive CTE. Hyposmia was more likely in the former players with TES who were either CTE Possible or Probable than in those who did not have TES or had TES but were less likely to have CTE, or CTE Suggestive. There was no difference in B-SIT scores between all former players versus unexposed men nor overall between the football players with and without TES. We conclude that lower B-SIT scores may be a clinical biomarker for underlying CTE in former American football players.

Background and Objective: Weight loss and small intestinal bacterial overgrowth (SIBO) are common in Parkinson’s disease (PD). We aimed to study the relationship between weight loss and SIBO in PD. Methods: This was a cross-sectional study with a prospective, interventional component. Consecutive patients seen in the PD clinic who agreed to participate underwent extensive history, movement exam, SIBO breath testing and answered questionnaires. A subset of those in the weight loss group were treated with rifaximin for 14 days and returned 3 months later for an assessment of their weight, GI symptoms, quality of life and SIBO status. All analyses were adjusted for age and disease duration. Results: Fifty-one patients participated in the study; 37 without weight loss and 14 with weight loss. Total energy intake including the distribution of macronutrient intake was similar between groups while physical activity was less in those with weight loss. PD severity scores did not differ between groups; however, PD-specific quality of life scores were significantly worse for the summary index and the subscales of emotional well-being, social support and communication. The prevalence of constipation, dyspepsia and abdominal pain/discomfort was higher in those with weight loss. The prevalence of SIBO was 14% in the weight loss group and was not different between groups. Eight PD patients with weight loss were treated with rifaximin; no significant change in GI symptoms, quality of life or weight was seen 3 months later. Conclusion: Although a number of differences were identified in quality of life and gastrointestinal symptoms between groups with and without weight loss, SIBO was not associated with weight loss in patients with PD. Given the exploratory nature and small number of patients with weight loss, however, further study is suggested.

AbstractBackgroundIdiopathic rapid eye movement sleep behavior disorder (RBD) is a strong known predictor of a final clinicopathological diagnosis of a Lewy type α‐synucleinopathy (LTS). Olfactory dysfunction is an early symptom of synucleinopathies and has been repeatedly associated with the presence of post‐mortem LTS.ObjectiveTo assess the combined value of a clinician diagnosis of probable RBD (PRBD) and hyposmia in predicting the post‐mortem presence of LTS in a broader, less‐selected, volunteer elderly population.MethodsWe studied 652 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders, which were evaluated for PRBD, had completed annual movement and cognitive assessments, and had at least one the University of Pennsylvania Smell Identification Test (UPSIT) olfactory test.ResultsHistological evidence of LTS was significantly more frequent in those who had PRBD (112/152: 73.7%) than those without (177/494: 35.8%) (P < 0.001). LTS was more frequent in cases with PRBD and a low UPSIT score (90.8%) compared to cases with PRBD only (73.7%) (P < 0.001) or cases with a low UPSIT score only (69.4%) (P < 0.001). Sensitivity of PRBD diagnosis for predicting LTS was 38.8% and specificity 88.8%, whereas sensitivity of a low UPSIT score was 74.4% and specificity 73.4% (Youden's index = 0.276 for PRBD, 0.478 for UPSIT). When combining both measures, sensitivity was 34.3% and specificity increased to 97.2%.ConclusionPRBD, diagnosed without sleep study confirmation, combined with a reduced olfactory performance is highly specific for predicting post‐mortem presence of LTS. The combination of both measures may provide a cost‐effective means of predicting LTS in a broader community.

Abstract Background and Objectives Gastric varices (GVs) are associated with a higher risk of uncontrolled bleeding and death when compared with esophageal varices. While endoscopic glue injection therapy has been traditionally used for secondary prophylaxis in GV, data regarding primary prophylaxis continue to emerge. Recently, EUS–guided therapies have been used in GV bleeding. Methods We conducted a comprehensive search of several major databases from inception to June 2022. Our primary goals were to estimate the pooled rates of treatment efficacy, GV obliteration, GV recurrence, and rebleeding with EUS-guided therapy in primary and secondary prophylaxis. Overall adverse events and technical failures were assessed. Random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I 2 % statistics. Results Eighteen studies with 604 patients were included. In primary prophylaxis, pooled rate of GV obliteration was 90.2% (confidence interval [CI], 81.1–95.2; I 2 = 0). With combination EUS–glue and coil therapy, the rate was 95.4% (CI, 86.7%–98.5%; I 2 = 0). Pooled rate of posttherapy GV bleeding was 4.9% (CI, 1.8%–12.4%; I 2 = 0). In secondary prophylaxis, pooled rate of treatment efficacy was 91.9% (CI, 86.8%–95.2%; I 2 = 12). With EUS-glue, EUS-coil, and combination EUS–glue and coil, the rates were 94.3% (CI, 88.9%–97.1%; I 2 = 0), 95.5% (CI, 80.3%–99.1%; I 2 = 0), and 88.7% (CI, 76%–95.1%; I 2 = 14), respectively. Pooled rate of GV obliteration was 83.6% (CI, 71.5%–91.2%; I 2 = 74). With EUS-glue, EUS-coil, and combination EUS–glue and coil, the rates were 84.6% (CI, 75.9%–90.6%; I 2 = 31), 92.3% (CI, 81.1%–97.1%; I 2 = 0), and 84.5% (CI, 50.8%–96.7%; I 2 = 75), respectively. Pooled rates of GV rebleeding and recurrence were 18.1% (CI, 13.1%–24.3%; I 2 = 16) and 20.6% (CI, 9.3%–39.5%; I 2 = 66), respectively. Conclusion Our analysis shows that EUS-guided therapy for GVs is technically feasible and clinically successful in both primary and secondary prophylaxis of GV.

Abstract Background Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. Methods We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. Results We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn’s disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P &lt; .001). Conclusions SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

Abstract Background and study aims Use of fluoroscopy in gastrointestinal endoscopy is an essential aid in advanced endoscopic interventions. However, it also raises concerns about radiation exposure. This study aimed to develop consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, prioritizing the safety and well-being of healthcare workers and patients. Methods A modified Delphi approach was employed to achieve consensus over three rounds of surveys. Proposed statements were generated in Round 1. In the second round, panelists rated potential statements on a 5-point scale, with consensus defined as ≥80% agreement. Statements were subsequently prioritized in Round 3, using a 1 (lowest priority) to 10 (highest priority) scale. Results Forty-six experts participated, consisting of 34 therapeutic endoscopists and 12 endoscopy nurses from six continents, with an overall 45.6% female representation (n = 21). Forty-three item statements were generated in the first round. Of these, 31 statements achieved consensus after the second round. These statements were categorized into General Considerations (n = 6), Education (n = 10), Pregnancy (n = 4), Family Planning (n = 2), Patient Safety (n = 4), and Staff Safety (n = 5). In the third round, accepted statements received mean priority scores ranging from 7.28 to 9.36, with 87.2% of statements rated as very high priority (mean score ≥ 9). Conclusions This study presents consensus-based statements for safe and effective use of fluoroscopy in gastrointestinal endoscopy, addressing the well-being of healthcare workers and patients. These consensus-based statements aim to mitigate risks associated with radiation exposure while maintaining benefits of fluoroscopy, ultimately promoting a culture of safety in healthcare settings.

Abstract Disclosure: S.W. Ing: Advisory Board Member; Self; Ultragenyx, Amolyt. Grant Recipient; Self; Alexion Pharmaceuticals, Inc.. Research Investigator; Self; BridgeBio Pharma, Takeda, Amolyt, Radius Health, Inc, Ultragenyx. P. Harmatz: Research Investigator; Self; BridgeBio Pharma. S. Mora: Research Investigator; Self; BridgeBio Pharma. E.A. Imel: Research Investigator; Self; BridgeBio Pharma. P.J. Tebben: Research Investigator; Self; BridgeBio Pharma. M.L. Warren: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt. Speaker; Self; Ascendis. N. Ma: Research Investigator; Self; Calcilytix Therapeutics, Ultragenyx, Inozyme. Other; Self; Up To Date. A.A. Khan: Research Investigator; Self; BridgeBio Pharma, Ascendis. A. Palermo: Research Investigator; Self; BridgeBio Pharma. B. Decallonne: Research Investigator; Self; BridgeBio Pharma. S. Lemoine: Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. G. Mantovani: Research Investigator; Self; BridgeBio Pharma. A. Linglart: Consulting Fee; Self; Alexion, Novo Nordisk, Merck, Pfizer, Inc.. Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. H. Wasserman: Research Investigator; Self; BridgeBio Pharma. A.P. Barbosa: Research Investigator; Self; BridgeBio Pharma. C. Cardot-bauters: Research Investigator; Self; BridgeBio Pharma. M. Roberts: Employee; Self; BridgeBio Pharma. A. Mathew: Employee; Self; BridgeBio Pharma. S. Adler: Employee; Self; BridgeBio Pharma. M.C. Zillikens: Research Investigator; Self; BridgeBio Pharma. R.J. Clifton-Bligh: Consulting Fee; Self; Ipsen, Kyowa Kirin, Amgen Inc, Eisai. Research Investigator; Self; BridgeBio Pharma. L. Rejnmark: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt, Takeda, Kyowa Kirin. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl &lt;250 women, &lt;300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1. Presentation: 6/3/2024

Abstract Disclosure: S.W. Ing: Research Investigator; Self; BridgeBio Pharma. P. Harmatz: Research Investigator; Self; BridgeBio Pharma. S. Mora: Research Investigator; Self; BridgeBio Pharma. E.A. Imel: Research Investigator; Self; BridgeBio Pharma. P.J. Tebben: Research Investigator; Self; BridgeBio Pharma. M.L. Warren: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt. Speaker; Self; Ascendis. N. Ma: Research Investigator; Self; Calcilytix Therapeutics, Ultragenyx, Inozyme. Other; Self; Up To Date. A.A. Khan: Research Investigator; Self; BridgeBio Pharma, Ascendis. A. Palermo: Research Investigator; Self; BridgeBio Pharma. B. Decallonne: Research Investigator; Self; BridgeBio Pharma. S. Lemoine: Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. G. Mantovani: Research Investigator; Self; BridgeBio Pharma. A. Linglart: Consulting Fee; Self; Alexion, Novo Nordisk, Merck, Pfizer, Inc.. Research Investigator; Self; BridgeBio Pharma, Kyowa Kirin. H. Wasserman: Research Investigator; Self; BridgeBio Pharma. A.P. Barbosa: Research Investigator; Self; BridgeBio Pharma. C. Cardot-bauters: Research Investigator; Self; BridgeBio Pharma. M. Roberts: Employee; Self; BridgeBio Pharma. A. Mathew: Employee; Self; BridgeBio Pharma. S. Adler: Employee; Self; BridgeBio Pharma. M.C. Zillikens: Research Investigator; Self; BridgeBio Pharma. R.J. Clifton-Bligh: Consulting Fee; Self; Ipsen, Kyowa Kirin, Amgen Inc, Eisai. Research Investigator; Self; BridgeBio Pharma. L. Rejnmark: Research Investigator; Self; BridgeBio Pharma, Ascendis, Amolyt, Takeda, Kyowa Kirin. Autosomal dominant hypocalcemia type 1 (ADH1), caused by gain-of-function calcium-sensing receptor gene (CASR) variants, is characterized by low parathyroid hormone (PTH) concentrations, hypocalcemia, hypercalciuria, hyperphosphatemia and hypomagnesemia. While a rare disease, ADH1 is one of the more frequently identified causes of genetic hypoparathyroidism. Conventional therapy includes calcium (Ca) and/or active vitamin D, but this regimen incompletely corrects the hypocalcemia and is associated with persistent hypercalciuria, which may result in renal complications including nephrocalcinosis (NC), nephrolithiasis (NL), and chronic kidney disease (CKD). The CLARIFY disease monitoring study [NCT05227287] is a global, multicenter, longitudinal study to understand disease burden, management, and progression in children and adults with ADH1 over a 5-year period. Here we report data on the characteristics of adult participants at study entry. As of November 2023, 45 adults (≥18 years) with ADH1 were enrolled, with a mean±SD age of 42.1±16.5 years (range 18-80). The mean±SD age of a hypocalcemia diagnosis was 19.1±19.1 years, while the mean±SD age for a diagnosis of ADH1 was 28.2±20.6 years. As reported on medical history, in decreasing order of prevalence, 36% (16) had NC, 22% (10) had intracranial calcifications, 11% (5) had history of seizures, 11% (5) had CKD, 9% (4) had cataracts, 7% (3) had NL, and 4% (2) had undergone renal transplant. Treatment data were available for 43 participants and included the following: 74% (32) Ca and active vitamin D, 9% (4) Ca alone, 9% (4) active vitamin D alone, 37% (16) magnesium, 33% (14) thiazide diuretics, 26% (11) potassium, 7% (3) phosphate binder, 7% (3) PTH, and 5% (2) no treatment. Mean±SD fasting values collected prior to conventional therapy dose are presented. PTH concentrations (10.1±8.2 pg/mL [nl 15-65]) and albumin-corrected calcium ([cCa]=7.5±1.0 mg/dL [nl 8.5-10.5]) were low. Despite the low mean cCa, the mean 24-hr urine calcium was elevated (268±183 mg/d, [nl &lt;250 women, &lt;300 men]). Blood phosphate was 4.8±0.8 mg/dL [nl 2.5-4.8] while blood magnesium was 1.8±0.2 mg/dL [nl 1.8-2.4]. 25-OH vitamin D was 35.0±13.5 ng/mL [nl 30-80]. Renal function as assessed by CKD-EPIcr_R showed eGFR of 86±23 mL/min/1.73m² (range 36-123). This study represents the largest cohort of adults with ADH1 described to date. These data highlight variability in therapeutic approaches in a real-world setting with some participants receiving up to 6 different medications/supplements. Despite being followed in expert centers, and treated with available therapies, patients on average have low cCa with relatively high 24-hr urine calcium excretion. The CLARIFY study provides an opportunity to better understand the progression and burden of disease in participants with ADH1. Presentation: 6/3/2024