bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent Chemotherapy and Pelvic Radiation Therapy Compared With Pelvic Radiation Therapy Alone as Adjuvant Therapy After Radical Surgery in High-Risk Early-Stage Cancer of the Cervix
Authors: Peters William A. , Liu P.Y. , Barrett Rolland J. , Stock Richard J. , Monk Bradley J. , Berek Jonathan S. , Souhami Luis , Grigsby Perry , Gordon William , Alberts David S. 
Published: October 2023

PURPOSE To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. PATIENTS AND METHODS Patients with clinical stage IA2, IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m2 and a 96-hour infusion of fluorouracil 1,000 mg/m2/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. RESULTS Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 ( P = .003) and 1.96 ( P = .007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. CONCLUSION The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.
FRI002 IGF-1R Targeting As A Strategy For Reducing Obesity And Improving Metabolism
Authors: Al-Samerria Sarmed , Farooq Saad , Candidate M S , Nandankar Nimisha , Negron Ariel Negron L , Radovick Sally 
Published: October 2023

Abstract
Disclosure: S. Al-Samerria: None. S. Farooq: None. N. Nandankar: None. A.L. Negron: None. S. Radovick: None.
There has been a significant increase in the prevalence of obesity over the past four decades, and it is projected that by 2030, the majority of the global population will fall into the overweight or obese categories if this trend continues. In a previous study, we reported that the ablation of the IGF-1R in GHRH neurons and somatotrophs (S-GIGFRKO) resulted in a sustained decrease in weight gain velocity due to increased lipolysis and higher energy expenditure, despite no changes in caloric intake. To evaluate the effects of a high-fat diet (HFD) on this metabolic phenotype, we challenged S-GIGFRKO mice with a 60% HFD beginning at 4 weeks of age. The S-GIGFRKO mice on the HFD showed normal linear growth, but after 8 weeks on the HFD, both males and females exhibited a sustained decrease in weight gain velocity compared to control mice on the HFD. Metabolic analysis revealed that the male and female S-GIGFRKO mice had higher oxygen consumption, lower carbon dioxide production, reduced body fat mass, increased energy expenditure, and improved glucose tolerance compared to the control mice on the HFD. No differences in food intake or total activity were observed between the two groups. These results demonstrate the important role of the GHRH-GH axis in regulating energy expenditure and fat metabolism, despite an environmental challenge induced by a HFD.
Presentation: Friday, June 16, 2023
FRI003 Oxytocin Response To Feeding Predicts Reward-driven Calorie Consumption In Adults With Obesity
Authors: Boutin Regine , Wronski Marie-Louis , Maso Ana Aulinas , Muhammed Maged , Galbiati Francesca , Kerem Liya , Carter Sue , Nazarloo Hans , Davis John M , Holman Katherine , Gydus Julia , Smith Sarah , Asanza Elisa , Plessow Franziska , Lawson Elizabeth Austen 
Published: October 2023

Abstract
Disclosure: R. Boutin: None. M. Wronski: None. A. Aulinas Maso: None. M. Muhammed: None. F. Galbiati: None. L. Kerem: None. S. Carter: None. H. Nazarloo: None. J.M. Davis: None. K. Holman: None. J. Gydus: None. S. Smith: None. E. Asanza: None. F. Plessow: None. E.A. Lawson: Consulting Fee; Self; OXT Therapeutics. Stock Owner; Self; OXT Therapeutics.
Objectives: Oxytocin (OXT) is a hypothalamic peptide hormone that reduces reward-related food intake and is under investigation as a potential weight loss therapy. Activation of OXT neurons in appetite pathways results in suppression of posterior pituitary release of OXT to the circulation, such that peripheral OXT levels (in response to feeding) may reflect the opposite of central OXT activity. While a relationship between peripheral OXT response to feeding and appetite has been reported in healthy females, there are no data related to OXT levels and appetite or eating behavior in individuals with obesity. We hypothesized that in individuals with obesity, higher OXT levels in response to feeding would be associated with greater reward-driven food intake assessed during a Cookie Taste Test. Methods: In a cross-sectional study of 53 adults with obesity (56% females; age [mean±SD] 33.7±6.2 years; BMI 36.9±4.9 kg/m2), participants presented after an overnight fast and were provided with a standard 400 kcal mixed meal. We sampled blood before and 30, 60 and 120 minutes after the meal for OXT levels and calculated area under the curve (AUC) as an integrated measure of OXT response to feeding. After receiving a subsequent snack, subjects ate as many cookies as needed to rate the cookies on various characteristics (i.e. sweetness, texture, delectability). We logarithmically transformed non-normal data to achieve a normalized distribution and used Pearson correlation to evaluate the relationship between OXT AUC and number of calories eaten during the Cookie Taste Test (behavioral marker of reward-related eating). Results: OXT AUC in response to a standardized meal predicted subsequent calories consumed at the Cookie Taste Test (R=0.30, p=0.036), such that those with higher OXT levels consumed more calories. Conclusions: Consistent with our hypothesis, peripheral OXT response to a standardized meal predicted subsequent reward-driven caloric intake in adults with obesity. These data suggest that endogenous OXT is involved in regulation of hedonic eating and supports targeting OXT pathways in the treatment of obesity.
Presentation: Friday, June 16, 2023
FRI021 Adipocyte Subpopulations Regulate The Lipolytic Response And Inflammatory Cytokine Action In Obesity
Authors: Huang Jun , Sharma Rita , Puri Vishwajeet , Lee Kevin Y 
Published: October 2023

Abstract
Disclosure: J. Huang: None. R. Sharma: None. K.Y. Lee: None.
Previously, our lab has utilized gene expression profiling and lineage tracing analysis to uncover three developmentally and functionally distinct subpopulations of white adipocytes with stable and unique gene expression profiles, which were termed Type 1, 2, and 3 adipocytes, respectively. This study extends these findings to investigate the role of Type 2 adipocytes in obesity. We found that the proportion of Type 2 preadipocytes and adipocytes in each adipose tissue was stable through time, but was dynamically regulated by high-fat diet (HFD) induced obesity in a depot-specific manner with a 59.34% increase in the perigonadal fat depots. Histological examination of fat depots after HFD-induced obesity revealed that over 80% of recruited macrophages, organized into crown-like structures, were found in direct contact with Type 2 adipocytes indicating increased necrosis or apoptosis of this adipocyte subpopulation. In addition, treatment of macrophage-derived inflammatory cytokine TNFα increased lipolysis specifically in Type 2 adipocytes by 11.9%, with no effects on other adipocytes. As previous studies have shown that inflammatory cytokines promote lipolysis in adipose tissue, at least in part, through the reduction of FSP27 (fat specific protein 27), we assessed the contribution of Type 2 adipocytes by overexpressing FSP27 specifically in this population (Type2Ad-hFSP27tg mice) during the development of obesity. We found that HFD-fed male Type2Ad-hFSP27tg mice had improved glucose tolerance and insulin sensitivity, with no change in body weight. These metabolic changes may, at least in part, be explained by the reduced basal and stimulated lipolysis rate in the visceral fat of Type2Ad-hFSP27tg mice compared with control mice. Although over-expression of FSP27 in primary Type 2 adipocytes is sufficient to acutely reduce TNFα-induced apoptosis, no reduction of macrophage infiltration was found in HFD-fed Type2Ad-hFSP27tg visceral fat after 18 weeks of HFD. Taken together, these results strongly suggest that adipocyte subpopulations contribute to the regulation of obesity-associated inflammation and lipolytic response in adipose tissue.
Presentation: Friday, June 16, 2023
FRI044 Racial Differences In Outcomes Of Hospitalizations For COVID-19 With Morbid Obesity: Insights From The National Inpatient Sample
Authors: Gajjar Rohan Ashwinbhai , Ahluwalia Daksh , Kumar Manoj , Rai Sumina , Shaka Hafeez , Stroger John H 
Published: October 2023

Abstract
Disclosure: R.A. Gajjar: None. D. Ahluwalia: None. M. Kumar: None. S. Rai: None. H. Shaka: None.
Introduction: The prevalence of obesity has risen across the globe over the past two decades and has remained high in the United States. In addition, obesity has surfaced as an independent risk factor for severe COVID-19 infection. We sought to investigate the impact of racial differences on hospitalizations for COVID-19 with morbid obesity using a nationally representative sample. Methods: The National Inpatient Sample database for 2020 was queried to identify adult hospitalizations with a primary diagnosis of COVID-19 and a secondary diagnosis of morbid obesity, using International Classification of Diseases – 10 Clinical Modification (ICD-10-CM) codes. The primary outcome studied was inpatient mortality, while secondary outcomes included inpatient complications, mean length of stay (LOS), and mean total hospital charge (THC). Multivariate logistic and linear regression analyses were used to adjust for possible confounders and to analyze the outcomes. Results: A total of 130,570 hospitalizations for COVID-19 with morbid obesity were identified, of which 48% were Caucasians, 25% were African Americans, and 19% were Hispanics. Our analysis revealed that Hispanics were associated with significantly higher adjusted odds of inpatient mortality (Adjusted Odds Ratio [aOR]: 1.4, [95% CI: 1.23-1.60], p &lt;0.001), increased mean LOS (1.25 days, [95% CI: 0.87-1.64], p &lt;0.001), and higher mean THC ($34,554, [95% CI: 25,316-43,791], p &lt;0.001) as compared to Caucasians; whereas African Americans had significantly lower adjusted odds of inpatient mortality (aOR: 0.85, [95% CI: 0.76-0.96], p=0.011) when compared to Caucasians. Additionally, complications such as sepsis (aOR 1.74, [95% CI: 1.50-2.03], p &lt;0.001), acute respiratory failure (ARF) (aOR: 1.15, [95% CI: 1.05-1.25], p=0.003), need for intubation (aOR: 1.27, [95% CI: 1.22-1.43], p &lt;0.001), mechanical ventilation (aOR: 1.26, [95% CI: 1.13-1.41], p &lt;0.001), requirement of pressor support (aOR: 1.74, [95% CI: 1.32-2.31], p &lt;0.001), the necessity of blood transfusion (aOR: 1.68, [95% CI: 1.40-2.02], p &lt;0.001) were significantly higher in Hispanics when compared to Caucasians. Conclusion: In this retrospective analysis of admissions for COVID-19 with morbid obesity, we discovered that the Hispanic subpopulation had elevated odds of mortality, along with a greater length of hospital stay and increased cost of hospitalization when compared to Caucasians. Additionally, Hispanics had higher odds of inpatient complications such as sepsis, ARF, need for mechanical ventilation/intubation, vasopressors, and blood transfusions. Our study highlights the existence of racial disparities that significantly affect outcomes in admissions for COVID-19 with morbid obesity.
Presentation: Friday, June 16, 2023
FRI048 Cardiometabolic Risk Markers In Children With Obesity And Variants In MC4R Pathway Related Genes
Authors: Salama Mostafa , Kumar Seema , e Vairo Filippo Pinto , Hentz Roland 
Published: October 2023

Abstract
Disclosure: M. Salama: None. S. Kumar: None. F. Pinto e Vairo: None. R. Hentz: None.
Objective: The association between disrupted melanocortin 4 receptor (MC4R) pathway function and childhood obesity is well established. Several variants in MC4R pathway related genes have been implicated to influence cardiometabolic parameters including lipid metabolism and glucose homeostasis. We compared the cardiometabolic risk markers in children with obesity and MC4R related clinically reported genetic variants relative to children with obesity and no MC4R related genetic variants. Methods: This was a retrospective case-control study conducted by chart review of children (age &lt;18 years) with obesity who underwent a multi-gene panel testing for monogenic obesity between February 2020 and November 2022. Children were divided into two groups according to their genetic test results: The first group was of children with clinically reported variants (pathogenic, likely pathogenic, risk allele or variant of uncertain significance) within the MC4R pathway), and the second group was of children with no reported variants in the MC4R pathway (negative genetic testing or variants in non-MC4R related genes). Data on systolic and diastolic blood pressure percentiles, fasting lipid panel, fasting blood glucose, hemoglobin A1c and ALT were extracted. Tests for group differences were performed using the independent two-sample t-test, Wilcoxon rank-sum test, Chi-Square test, or Fisher’s exact test as appropriate for each variable type and test assumptions. Results: Data on a total of 91 children were reviewed. Mean age at testing was 11 years (SD: 4) and mean peak BMI% of the 95th percentile was 158 (SD: 28). 36 patients had clinically reported variants in the MC4R pathway, and 55 patients had no reported MC4R related variants. The blood pressure percentiles, fasting glucose, hemoglobin A1C, total cholesterol, high density lipoprotein cholesterol and low-density lipoprotein cholesterol were not different between both groups. Conclusion: In this pilot study, among children with obesity, variants in the MC4R pathway related genes were not associated with cardiometabolic risk markers. Larger studies are warranted to assess the correlation between MC4R pathway genes and cardiometabolic risk.
Presentation: Friday, June 16, 2023
SAT648 The Role Of Olfactory Marker Protein On Adipogenesis
Authors: Bao Yaru , Cho Yoon Hee , Lee Eun Jig 
Published: October 2023

Abstract
Disclosure: Y. Bao: None. Y. Cho: None. E. Lee: None.
Olfactory marker protein (OMP) plays a role in regulating the of olfactory transduction but is also expressed in adipose tissue. OMP serves as a regulating buffer for cyclic AMP (cAMP) levels; thus, we hypothesized that Omp may play a role in modulating adipocyte differentiation, a cAMP-dependent process. To determine the role of OMP in adipogenesis, we examined the differences in body weight, adipose tissue mass, and adipogenic or thermogenic gene expression of normal and Omp-knockout (KO) mice fed a high-fat diet. The cAMP production, adipogenic gene expression, and cAMP response element binding protein (CREB) phosphorylation were measured during differentiation in 3T3-L1 preadipocytes and mouse embryonic fibroblasts (MEFs). Finally, RNA sequencing was performed to find out why adipogenesis was reduced when Omp was deleted. We observed a decrease in body weight, adipose tissue mass, and the size of adipocytes in Omp-KO mice. We confirmed low cAMP production and CREB phosphorylation in adipogenesis induced in Omp-/- MEFs, and nuclear factor kappa B activation due to significantly reduced IκBα expression. Collectively, our results suggest that loss of OMP function inhibits adipogenesis through affecting adipocyte differentiation.
Presentation: Saturday, June 17, 2023
SAT136 Severe Lactic Acidosis Due To Metformin Use.
Authors: Khan Areej 
Published: October 2023

Abstract
Disclosure: A. Khan: None.
Lactic acidosis is an important cause of metabolic acidosis. Broadly, etiology can be divided into type A (impaired tissue oxygenation), type B (systemic hypoperfusion), and D-lactic acidosis. One such etiology which deserves mentioning is metformin associated lactic acidosis (MALA). The incidence of MALA is more notable in the setting of kidney dysfunction, hepatic failure, and alcohol use. Severe acidosis due to Metformin is an emergency and warrants timely management to avoid further hemodynamic compromise. 73-year-old female with a history of hypertension and type II diabetes mellitus (on metformin) presented to the hospital with acute onset of abdominal pain, nausea, and vomiting. She reported having intermittent vomiting and diarrhea for three days prior to admission, and describes the abdominal pain as 10/10, sharp with radiation to the lower back, and worsening 6 hours prior to arrival. She denies fever, melena, hematochezia, change in appetite. She was brought to the hospital via EMS and was given fentanyl for her pain. Vitals on arrival were stable. On exam, she appeared in distress due to pain, with diffuse tenderness in her abdomen, with normal cardiac and lung exam. Labs showed leukocytosis 15 K/mm3, hemoglobin 11.1 gm/dl, hyperkalemia 5.7 mEq/L, bicarb &lt;5 mEq/L, creatinine 13.4 mg/dl, BUN 107 mg/dl, venous lactate 15.1 mmol/l, lipase 435 U/L, ammonia 229 umol/L, with normal AST, ALT and ALP, and troponin. Urinalysis was negative. Initial ABG showed an unreadable pH, which was then repeated, and pH was noted to be 6.72, pCO2 of 29.4 mm/hg, CTA angiography was negative for dissection, mesenteric or bowel ischemia. Soon she was noted to be hypotensive and went into shock requiring pressors, bicarbonate drip, and broad-spectrum antibiotics. She eventually was intubated for airway protection. Subsequently, she was admitted to the ICU for possibly combined hypovolemic and septic shock with multi-organ dysfunction, severe lactic acidosis, acute kidney failure, and respiratory failure. Nephrology was consulted and dialysis was initiated. It was postulated that the presentation was likely due to metformin associated lactic acidosis (MALA). She required dialysis daily for 4 days and ultimately her kidney function improved. On discharge, she was not dialysis dependent. The case above illustrates the severity of lactic acidosis that can occur due to Metformin use. It is important to bear in mind that such presentation, may not necessarily occur on initiation of Metformin, but rather at any point of use. More importantly, its of utmost importance to consider effective therapeutic options like dialysis once severe academia is noted to allow correction of metformin induced acid-base disorder. Mortality estimates of MALA have been around 25-50%, highlighting the significance of prompt treatment of this condition.
Presentation: Saturday, June 17, 2023
SAT141 A Case Of Non-islet Cell Tumor Hypoglycemia Which Was Ameliorated By Pazopanib Treatment
Authors: Yamamoto Naoki , Yamamoto Masaaki , Kiyota Naomi , Inaba Yuiko , Kanie Keitaro , Urai Shin , Suzuki Masaki , Sasaki Yuriko , Oi Yuka , Tsujimoto Yasutaka , Motomura Yuma , Ohmachi Yuka , Bando Hironori , Iguchi Genzo , Nagao Mototsugu , Fukuda Izumi , Fukuoka Hidenori , Ogawa Wataru 
Published: October 2023

Abstract
Disclosure: N. Yamamoto: None. M. Yamamoto: None. N. Kiyota: None. Y. Inaba: None. K. Kanie: None. S. Urai: None. M. Suzuki: None. Y. Sasaki: None. Y. Oi: None. Y. Tsujimoto: None. Y. Motomura: None. Y. Ohmachi: None. H. Bando: None. G. Iguchi: None. M. Nagao: None. I. Fukuda: None. H. Fukuoka: None. W. Ogawa: None.
Introduction: Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome caused by insulin-like growth factor II (IGF-II) hypersecretion from the tumors. It is characterized by incompletely processed big IGF-II with potent insulin-like activity. We present a case of NICTH complicated with solitary fibrous tumor (SFT) which was ameliorated with the administration of pazopanib, a multi-targeted tyrosine kinase inhibitor. Clinical Case: A 57-year-old man went into a coma and was hospitalized. His plasma glucose levels were 26 mg/dL, and he regained consciousness after glucose administration, leading to a diagnosis of hypoglycemic coma. Moreover, a contrast-enhanced CT scan showed multiple tumors in his liver and right kidney. He was referred to our hospital for further management. After 5 hours of fasting, he had a cold sweat, and his plasma glucose levels dropped to 32 mg/dL with suppressed serum insulin levels of 0.2 U/mL. Serum 3-hydroxybutyrate levels were as low as 21 μmol/L, and plasma glucose levels increased to 83 mg/dL after glucagon administration, suggesting an agent mimicking insulin. Percutaneous liver biopsy was performed, and the tumors were diagnosed with SFT. Immunoblotting for his serum showed big IGF-II, leading to a diagnosis of NICTH, and hypoglycemia due to hypersecretion of IGF-II. Due to multiple metastases, surgery was not indicated and pazopanib was administered. Hypoglycemia during the night was prevented by glucose infusion through the central venous port, and he was discharged. Three months later, when he was re-hospitalized for thrombophlebitis of the right jugular vein, hypoglycemia did not occur even after 10 hours of fasting and CT scan showed the necrotic change of the tumor. Two weeks later of pazopanib discontinuation due to the thrombogenic adverse effect, hypoglycemia recurred accompanied by the tumor enlargement. When the anticoagulation therapy regressed the thrombosis and pazopanib was re-administered, hypoglycemia improved reproducibly and remained stable for more than 2 years although the tumor showed gradual progression. Conclusion: This is the first case in which pazopanib was effective in suppressing NICTH associated with SFT.
Presentation: Saturday, June 17, 2023