bluuebunny/crossref_metadata_2025_split huggingface dataset:
7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon
Authors: Fedorko J , Subarajan P , Amblee A P , Poku C A 
Published: October 2024

Abstract
Disclosure: J. Fedorko: None. P. Subarajan: None. A.P. Amblee: None. C.A. Poku: None.
Background: The term ‘pseudohypoglycemia’ is used to describe the disparity between actual and measured capillary glucose and clinical presentation. It has been used to describe situations when a patient has the characteristic symptoms of low blood glucose (BG) Whipple’s triad), but the patient’s BG levels are within normal limits. Alternatively, this term can also be used to describe falsely low BG levels on finger-stick (capillary) readings in a patient with normal serum glucose levels and without the characteristic Whipple’s triad. Case: A 55-year-old female with Raynaud’s phenomenon was seen in Endocrine clinic with persistent hypoglycemia noted on finger-stick glucose readings. Her finger-stick glucose reading was 43, and was subsequently given 24 grams of glucose gel. Ten minutes later, a repeat finger stick BG was 44. She had no weakness, tremors, shakiness, vision changes, confusion, seizures, lightheadedness, dizziness, tachycardia, palpitations, nervousness, hunger, paresthesias irritability, confusion, seizures, loss of consciousness, or any other symptoms or signs of hypoglycemia. She had no such previous episodes and her fasting BG ranged from mid-70s to 80, with post-meal BG ranging from 100 to mid-100’s. Her most recent hemoglobin A1c was 5.5. She regularly experiences cyanosis of fingers consistent with Raynaud’s phenomenon, triggered by cold air in winter and air conditioners in summer. She does not take any medications for these episodes. Given the absence of classic Whipple triad and normal BG from peripheral blood draw, the patient’s low finger stick BG readings were attributable to Raynaud’s phenomenon. It is postulated to be secondary to decreased perfusion in the digital microcirculation and increased blood transit time in the fingers, resulting in a local increase in glucose consumption and thus low capillary finger stick BG levels. Simultaneously done serum glucose levels are usually normal. Conclusion: Pseudohypoglycemia can occur in patients with impaired peripheral circulation such as Raynaud’s phenomenon, acrocyanosis, peripheral vascular disease, shock, or with increased glycolysis by blood cells like in leukemia, polycythemia and rare infections like African trypanosomiasis, hyperviscosity syndromes like Waldenstrom’s and monoclonal gammopathy of undetermined significance. In patients with low finger-stick (capillary) glucose levels who do not display Whipple’s triad, and have comorbid conditions that might interfere with the BG reading, it is important for clinicians to recognize the difference between true and pseudohypoglycemia. This can be confirmed with a simultaneously done normal serum glucose level and will prevent unnecessary investigations or excessive treatment.
Presentation: 6/3/2024
8654 Real-World Performance Of The Medtronic Extended Infusion Set In The United States
Authors: Kwa Timothy , Zhang Gina , Kiehl Justin , Putcha Venkat , Patel Anuj , Chattaraj Sarnath , Cohen Ohad , Vigersky Robert Alan 
Published: October 2024

Abstract
Disclosure: T. Kwa: Employee; Self; Medtronic Minimed. G. Zhang: Employee; Self; Medtronic Minimed. J. Kiehl: Employee; Self; Medtronic Minimed. V. Putcha: Employee; Self; Medtronic Minimed. A. Patel: Employee; Self; Medtronic Minimed. S. Chattaraj: Employee; Self; Medtronic Minimed. O. Cohen: Employee; Self; Medtronic Minimed. R.A. Vigersky: Employee; Self; Medtronic Minimed.
Real-World Performance of the Medtronic Extended Infusion Set in the United States Objective: The Medtronic extended infusion set (EIS) is the first and only infusion set approved for up to 7-day use and its pivotal trial established clinical safety and efficacy.[1] The purpose of this retrospective analysis was to assess real-world EIS performance and overall glycemic outcomes based on United States (US) data uploaded by MiniMed™ 770G system (MM770G) users at an aggregate level. Methods: Infusion set occlusion alarm events and time in (TIR, 70-180 mg/dL), below (TBR, &lt;70 mg/dL) and above (TAR, &gt;180 mg/dL) range of EIS-MM770G users (N=393) with &gt;30-day device use in the U.S. were analyzed and compared against the data of a cohort of the same median age of 50 years (N=77219) using the MM770G with a standard 2/3-day infusion set (at an aggregate level). Results: EIS users experienced a lower occlusion alarm rate (median 0.011 alerts/patient day) compared to 0.016 alerts/patient day with the standard set (p = 0.005). TIR for EIS users was 69.4%, which was numerically greater than the 69.1% for standard set users (p = 0.258). While TAR was not significantly different (28.9% for EIS and 29.0% for standard set, p = 0.995), TBR was significantly lower (0.5% for EIS and 1.3% for standard set, p = 0.000). The difference in the total daily dose (TDD) of insulin between the two groups (53.0 units for EIS, 49.4 units for standard set) was not statistically significant (p = 0.961). Conclusion: Since the U.S. launch, the EIS has continued to perform similarly to the pivotal trial results and an early real-world analysis of EIS use outside of the US.2 The decreased burden of fewer set changes comes with a lower occlusion alarm rate and does not compromise time spent in target range. References: 1.Brazg R, et al. Diabetes Technol Ther. 2022;24:535-543. 2.Kwa T, et al. Diabetes. 2023;72(Supplement_1):910-P.
Presentation: 6/1/2024
12421 Reduced ZMPSTE24 Expression Leads To Prelamin Accumulation And Development Of Steatosis In MASLD Patients
Authors: Schinderle Joseph , Bochkis Irina , Wu Anqi 
Published: October 2024

Abstract
Disclosure: J. Schinderle: None. I. Bochkis: None. A. Wu: None.
Reduced ZMPSTE24 expression leads to prelamin accumulation and development of steatosis in MASLD patients. Joseph D. Schinderle[1],[2], Anqi Wu[1],[2], Irina M. Bochkis[1],[2]* [1] Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261 [2] Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261 We have previously observed changes at the nuclear lamina in MASLD patients that led to redistribution of lamina-associated domains and reshaping of FOXA2 binding with progression of steatosis. Here we report that the changes at the nuclear envelope are caused by downregulation of ZMPSTE24, an enzyme that processes prelamin to mature lamin A, leading to accumulation of prelamin in MASLD patients. Mutations of LMNA and ZMPSTE24 have been associated with fatty liver. In addition, Zmpste24 mutant mice develop hepatic steatosis and Zmpste24 deficiency is linked to upregulation of p53 target genes. Ingenuity Pathway Analysis determined upregulated p53 activity in genes differentially expressed in both male and female MASLD patients. Furthermore, upstream analysis identified p53 as a regulator of genes bound by FOXA2 in these individuals, corresponding to observations in Zmpste24 knockout animals. Additional regulator analysis of RNA-Seq determined that genes regulated by glucose and insulin to be downregulated in MASLD patients, suggesting altered glucose metabolism and insulin resistance, hallmarks of type 2 diabetes (T2D). Hence, our genomics data shows that MASLD patients with severe steatosis that have yet to progress to MASH are already suffering from severe metabolic consequences and underscores the need for treatment at this stage of the disease.
Presentation: 6/2/2024
8016 Resolution of Refractory Hypoglycemia Following Pancreatic Solitary Fibrous Tumor Resection
Authors: Horowitz Maxwell Ethan , Stefan Simona 
Published: October 2024

Abstract
Disclosure: M.E. Horowitz: None. S. Stefan: None.
Introduction: Solitary fibrous tumors (SFT) are exceptionally rare mesenchymal tumors, accounting for only 3.7% of all cases of soft-tissue sarcoma with an incidence of 0.35 cases per 100,000 persons per year. SFT may arise in various anatomical locations, approximately 30% occuring in the abdomen. SFT can manifest with paraneoplastic syndromes, with the most commonly described being non-islet cell hypoglycemia. We present a case of refractory hypoglycemia which resolved following the resection of a large pancreatic SFT. Clinical Case: A 75-year-old male with a history of hypertension presented from oncology clinic with hypoglycemia. Two weeks prior, a 26cm mass of the pancreatic head was identified after he presented to the hospital for one month of abdominal pain and distention, and biopsy of the mass confirmed an SFT. The patient complained of nighttime weakness, confusion, nausea, vomiting, and urinary incontinence for two nights prior to arrival. During this time, the patient had multiple fingersticks showing hypoglycemia below 70 mg/dL, the lowest at 37 mg/dL. On arrival, fingerstick glucose was 38 mg/dL and serum glucose was 27 mg/dL, with a c-peptide level of 0.28 ng/mL (1.00-4.00 ng/mL). Despite hypoglycemia, he was asymptomatic at the time of presentation, indicating hypoglycemia unawareness. Investigation into the cause of hypoglycemia included normal morning cortisol levels, normal thyroid function tests, and normal liver and renal function tests. Further assessment for paraneoplastic disease was conducted, revealing an IGF1 level of 36 ng/dL (5-34 ng/dL) and IGF2 241 ng/dL (267-616 ng/dL), with a ratio of IGF2:IGF1 of 6.7:1. He underwent surgical removal of the large abdominal mass with distal gastrectomy and Billroth-I reconstruction. Pathology was consistent with a 34cm retroperitoneal SFT, STAT6 positivity, and negative margins. Following surgery, the patient did not experience any further hypoglycemia or related symptoms, and glucose ranged 78-135 mg/dL through discharge. Clinical Lessons: Refractory hypoglycemia resulting from a tumor's production of IGF2 is a rare paraneoplastic syndrome known as Doege-Potter Syndrome. This syndrome is observed in fewer than 5% of patients with SFT. The first documented case of hypoglycemia in a patient with "fibrous sarcoma" dates back to 1930. To establish a diagnosis, a ratio of IGF2:IGF1 exceeding 3:1 is suggestive of tumor-mediated production, while a ratio exceeding 10:1 is considered diagnostic. A positive immunohistochemical stain for STAT6 confirms the diagnosis. Patients with these tumors should be routinely monitored for hypoglycemia and related symptoms.
Presentation: 6/3/2024
8327 Risk Of Chronic Kidney Disease In Subjects With Metabolic Dysfunction-Associated Fatty Liver Disease Or Metabolic Dysfunction-Associated Steatotic Liver Disease: A Retrospective Study
Authors: Rhee E J , Kwon H , Park S , Lee W Y 
Published: October 2024

Abstract
Disclosure: E. Rhee: None. H. Kwon: None. S. Park: None. W. Lee: None.
Background: Recently, the term non-alcoholic fatty liver disease (NAFLD) is replaced by a new term, metabolic dysfunction-associated liver disease (MASLD), with a new definition made by a modified Delphi process led by three large pan-national liver associations. In this study, we aimed to analyze the risk for chronic kidney disease (CKD) development in those with MASLD defined by the new definition and metabolic dysfunction-associated fatty liver disease (MAFLD). Methods: Among 52,606 participants (mean age 35.4 years) in the health checkup program from 2002 to 2019, in whom at least 10 health checkups were performed, after strict exclusion, 48,751 participants were enrolled and analyzed the development of CKD defined by estimated glomeruls filtration lower than 60 mL/min/1.73m2) during a median of 14.7 years of follow-up. The presence of MAFLD was defined by presence of hepatic steatosis plus one of the three criteria of overweight or obese, type 2 diabetes or presence of ≥2 metabolic risk abnormalities. MASLD was defined by presence of hepatic steatosis plus at least 1 of 5 cardiometabolic risk factors. Results: At baseline, 12,773(26.2%) participants had MAFLD and 35,359(74.58%) had MASLD. During the follow-up period, 849(1.7%) participants developed CKD. In participants with MAFLD, 345(2.7%) participants developed CKD, and in participants with MASLD, 609(1.7%) developed CKD. After adjustment for age and sex, the hazard ratio(HR) of CKD was 1.44 (95% confidence interval [CI] 1.25-1.66) for MAFLD, and 1.25(95% CI 1.07-1.47) for MASLD. Both definition predicted development of CKD nicely (Harrell’s C-index: 0.79(0.77-0.81) for MAFL and MASLD) Conclusions: The participants with MAFLD and MASLD showed significantly increased risk for CKD during a median of 15 years of follow-up. Both criteria showed nice predictability for CKD.
Presentation: 6/1/2024
9215 Role Of Insulin/IGF1 Signaling And FoxO Transcription Factors In Satellite Cell And Skeletal Muscle Development And Senescence
Authors: Yu Yingying(Joy) , Wang Guoxiao , O'Neill Brian Timothy , Kahn Carl Ronald 
Published: October 2024

Abstract
Disclosure: Y. Yu: None. G. Wang: None. B.T. O'Neill: None. C.R. Kahn: None.
Aging is associated with loss of skeletal muscle mass, deficiency of satellite cell (SC) function, and increase in intramuscular adipose tissue (IMAT) and insulin resistance posing threats to health and quality of elder life. Insulin / IGF1 signaling and their downstream signaling pathways play crucial roles in muscle function, as well as longevity a broad range of species. To identify the role of Insulin / IGF1 signaling in skeletal muscle homeostasis and aging/senescence, we took advantage of Cre-loxp mouse model using Pax7-Cre or HAS-Cre mice cross with insulin receptor (IR) and IGF1 receptor (IGF1R) double flox mice to create IR/IGF1R double knockout mice in both muscle progenitors (satellite cells) and mature skeletal muscle cells. We refer to the PaxCreIRIGF1RKO as the P7DKO and HSACreIRIGF1RKO as simply the DKO. Both P7DKO and DKO mice show severe loss of skeletal muscle with increased markers of cellular senescence and increased IMAT infiltration. This was indicated by a 60% loss of muscle mass, morphological evidence of skeletal muscle with atrophy and increased adipocyte infiltration, with a &gt;6-fold increase of adipocyte marker Perlipin1. The muscle also exhibited 2- to 10-fold increases of cellular senescence and senescence-associated secretory markers, including Cdkn1a, Cdkn2a, Trp53, CD68, Cxcl14, and Ccr2. Both the whole skeletal muscle and primary satellite cells isolated from P7DKO mouse muscle show a higher level of senescence-associated beta-galactosidase, as compared to the cells from littermate controls. This was accompanied by a deficiency of proliferation and differentiation of the satellite cells. Interestingly, simultaneous knockout of Foxo1/3/4 in the DKO mouse muscle rescued the muscle atrophy, reduced IMAT infiltration and reduced skeletal muscle cell senescence. Thus, insulin/IGF1 signaling in satellite cells and mature muscle cells plays not only an important role in skeletal muscle development, but also skeletal muscle cell senescence, and this is mediated, in large part, through FOXO transcription factors. This pathway and these proteins provide both new insights and potential targets for improving skeletal muscle homeostasis and function in the elderly.
Presentation: 6/2/2024
7897 Role Of Insulin/IGF1 Signaling And FoxO Transcription Factors In Satellite Cell And Skeletal Muscle Development And Senescence
Authors: Yu Yingying(Joy) , Wang Guoxiao , O'Neill Brian Timothy , Kahn Carl Ronald 
Published: October 2024

Abstract
Disclosure: Y. Yu: None. G. Wang: None. B.T. O'Neill: None. C.R. Kahn: None.
Aging is associated with loss of skeletal muscle mass, deficiency of satellite cell (SC) function, and increase in intramuscular adipose tissue (IMAT) and insulin resistance posing threats to health and quality of elder life. Insulin / IGF1 signaling and their downstream signaling pathways play crucial roles in muscle function, as well as longevity a broad range of species. To identify the role of Insulin / IGF1 signaling in skeletal muscle homeostasis and aging/senescence, we took advantage of Cre-loxp mouse model using Pax7-Cre or HAS-Cre mice cross with insulin receptor (IR) and IGF1 receptor (IGF1R) double flox mice to create IR/IGF1R double knockout mice in both muscle progenitors (satellite cells) and mature skeletal muscle cells. We refer to the PaxCreIRIGF1RKO as the P7DKO and HSACreIRIGF1RKO as simply the DKO. Both P7DKO and DKO mice show severe loss of skeletal muscle with increased markers of cellular senescence and increased IMAT infiltration. This was indicated by a 60% loss of muscle mass, morphological evidence of skeletal muscle with atrophy and increased adipocyte infiltration, with a &gt;6-fold increase of adipocyte marker Perlipin1. The muscle also exhibited 2- to 10-fold increases of cellular senescence and senescence-associated secretory markers, including Cdkn1a, Cdkn2a, Trp53, CD68, Cxcl14, and Ccr2. Both the whole skeletal muscle and primary satellite cells isolated from P7DKO mouse muscle show a higher level of senescence-associated beta-galactosidase, as compared to the cells from littermate controls. This was accompanied by a deficiency of proliferation and differentiation of the satellite cells. Interestingly, simultaneous knockout of Foxo1/3/4 in the DKO mouse muscle rescued the muscle atrophy, reduced IMAT infiltration and reduced skeletal muscle cell senescence. Thus, insulin/IGF1 signaling in satellite cells and mature muscle cells plays not only an important role in skeletal muscle development, but also skeletal muscle cell senescence, and this is mediated, in large part, through FOXO transcription factors. This pathway and these proteins provide both new insights and potential targets for improving skeletal muscle homeostasis and function in the elderly.
Presentation: 6/2/2024
7967 Ruxolitinib Prevents Immune-Checkpoint Inhibitor-Related Diabetes Mellitus Via Inhibition Of Pathogenic IL-21 And IFNγ-Producing CD4+ T Cells
Authors: Huang N L , Ortega J , Wang S J , Scott L N , Kimbrell K , McCarthy E , Olay J , Nguyen J N , Kim K , Lee J , Lechner M G 
Published: October 2024

Abstract
Disclosure: N.L. Huang: None. J. Ortega: None. S.J. Wang: None. L.N. Scott: None. K. Kimbrell: None. E. McCarthy: None. J. Olay: None. J.N. Nguyen: None. K. Kim: None. J. Lee: None. M.G. Lechner: None.
The use of immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment landscape for many advanced cancers by leveraging immune activation through the blockade of checkpoint proteins, including programmed death protein-1 (PD-1). Unfortunately, autoimmune attack of healthy tissue can occur in up to 60% of patients. ICI-induced Type 1 diabetes mellitus (ICI-T1DM) is a rare but life-threatening adverse event during ICI therapy that leads to rapid destruction of pancreatic islets, hyperglycemia, and lifetime dependence on insulin. While cytotoxic CD8+ T cells are recognized as important players in ICI-T1DM, the role for CD4+ helper T cells in disease pathogenesis is less well understood. Using a mouse model of ICI-autoimmunity, in which male and female NOD mice treated with anti-PD-1 (10mg/kg/day, i.p., twice weekly) develop multi-organ autoimmune infiltrates including insulitis and DM, we identified interleukin-21 (IL-21) and interferon gamma (IFNγ) CD4+ T cells as key contributors to ICI-T1DM. Antibody depletion of CD4+ T cells in NOD mice significantly delayed the onset of ICI-T1DM. Immunophenotyping of pancreatic islet infiltrates in ICI-treated mice revealed increased IL-21+ IFNγ+ CD4+ T follicular helper (Tfh; ICOS+ PD1+ CXCR5+) and T peripheral helper (Tph; ICOS+PD1+ CXCR5- CXCR6+) cells. In vitro, IL-21 increased effector CD8+ T cell function and IFNγ promoted production of T cell-attracting chemokines CXCL9, CXCL10, and CXCL16 by macrophages. Given the potential role for IL-21 and IFNγ to amplify ICI-DM progression, we sought to target these signaling pathways as potential interventions. Genetic inhibition of IL-21 or IFNγ signaling in NOD mice reduced insulitis and DM in anti-PD-1 treated mice. Considering that IL-21 and IFNγ act through JAK/STAT signaling in immune cells, we proposed to block this pathway to prevent ICI-DM using ruxolitinib, a clinically available JAK1/2 inhibitor. Indeed, ruxolitinib blocked STAT3 and STAT1 phosphorylation in mouse splenocytes in response to IL-21 or IFNγ, respectively, and completely protected ICI-treated NOD mice from DM. Finally, in a syngeneic tumor model, use of ruxolitinib after initiation of anti-PD-1 therapy did not abrogate ICI anti-tumor effects. Taken together, these data suggest that IL-21 and IFNγ producing CD4+ T cells are important drivers of ICI-T1DM, and that the use of JAK inhibitors may be a promising clinical intervention to reduce ICI-T1DM toxicities in patients.
Presentation: 6/2/2024
8035 Severe Hyperglycemia Induced By Enfortumab Vedotin (EV) Treatment For Urothelial Carcinoma
Authors: Semreen Noura , Goldberg Michael David 
Published: October 2024

Abstract
Disclosure: N. Semreen: None. M.D. Goldberg: None.
Introduction: Immunotherapy has revolutionized cancer treatment, but it has a wide range of adverse events including endocrinopathies. Here we present a case of severe hyperglycemia induced by enfortumab vedotin (EV) treatment for advanced urothelial carcinoma. Clinical Case: A 56-year-old male was admitted to our hospital with a painful rash in sun-exposed areas. He had metastatic urothelial carcinoma, with progression of disease after platinum-based chemotherapy, radiation therapy, and pembrolizumab, and had begun treatment with EV six weeks prior to presentation. He also had type 2 diabetes mellitus, with a recent A1c of 6.1% on metformin monotherapy, and obesity (BMI, 31 kg/m2). His blood glucose on admission was 600 mg/dL, and insulin therapy was initiated. There was no evidence for DKA or HHS. Over the course of his 9-day admission he required approximately 200 units of insulin per day to control his glucose. A fasting C-peptide level was 6.89 ng/mL (0.81-3.89 ng/mL) concurrent with a glucose of 181 mg/dL. Skin biopsy revealed erythema multiforme, which represented a grade 4 toxicity of EV treatment, and the EV was discontinued. Symptoms improved with oral glucocorticoids. The patient was discharged on multiple daily injections of insulin in addition to metformin. His insulin requirements fell rapidly, and one month later he was able to discontinue insulin completely. He was started on sacituzumab for his cancer treatment. Discussion: EV is a first-in-class antibody-drug conjugate directed against Nectin-4, which was approved in 2019 for previously treated locally advanced or metastatic urothelial carcinoma. Hyperglycemia was reported in 6.4% of patients receiving EV in the initial phase III study; BMI ≥ 30 kg/m2 and pretreatment A1c ≥ 6.5% were identified as risk factors. In a 24-month follow-up analysis, the incidence of grade ≥ 3 hyperglycemia was 4.4%, and the median time to onset of hyperglycemia was 19 days. There have been postmarketing reports of EV-induced DKA, as well as cases of refractory hyperglycemia requiring more than 1,000 units of insulin daily. The mechanism explaining the hyperglycemia is not yet defined, but in the prior case reports, as well as the current case, C-peptide levels have been elevated. It is assumed, therefore, that the mechanism involves insulin resistance as opposed to insulin deficiency. The marked hyperglycemia appears to be reversible once EV therapy is discontinued. In 2023, EV was approved in combination with pembrolizumab for first-line therapy of locally advanced or metastatic urothelial cancer, as an alternative to platinum-based chemotherapy. With this expanded indication, providers should be aware of the risk of hyperglycemia, which in some cases may be severe.
Presentation: 6/3/2024