bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophageal cancer surgery: a randomized clinical trial
Authors: Wang Wu , Xie Jin-biao , Yang Tian-bao , Huang Shi-jie , Chen Bo-yang
Published: October 2023

Background

This study aims to investigate the outcomes of patients who received early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy due to esophageal cancer.

Methods

A prospective randomized clinical trial was performed between March 2020 and June 2022. Patients who were scheduled for thoracoscopic and laparoscopic esophagectomy due to esophageal cancer were enrolled. Then, these patients were assigned to the control group (traditional postoperative care) and study group (traditional postoperative care with early bronchoscopic sputum aspiration and lavage). The outcomes, which included the length of hospital stay and medical expenses, and postoperative complications, which included pulmonary infection, atelectasis, respiratory dysfunction and anastomotic leakage, were compared between these two groups.

Results

A total of 106 patients were enrolled for the present study, and 53 patients were assigned for the control and study groups. There were no statistically significant differences in gender, age, and location of the esophageal cancer between the two groups. Furthermore, the length of hospital stay was statistically significantly shorter and the medical expenses were lower during hospitalization in the study group, when compared to the control group (12.3 ± 1.2 vs. 18.8 ± 1.3 days, 5.5 ± 0.9 vs. 7.2 ± 1.2 Chinese Yuan, respectively; all, P < 0.05). Moreover, there were statistically significantly fewer incidences of overall complications in study group, when compared to the control group (20.7% vs.45.2%, P < 0.05).

Conclusions

For patients with esophageal cancer, early fiberoptic bronchoscopic sputum aspiration and lavage after thoracoscopic and laparoscopic esophagectomy can shorten the length of hospital stay, and lower the medical expense and incidence of postoperative complications.
Redo mitral valve replacement in an adult with severe pulmonary hypertension resulting from structural valve deterioration and left ventricular outflow tract obstruction and a history of atrioventricular septal defect repair: a case report
Authors: Sugiyama Kayo , Matsuyama Katsuhiko , Ogino Hitoshi
Published: October 2023

Background

Pulmonary hypertension (PH)-associated with left heart disease (Nice PH classification group II) improves when the latter is treated; however, the treatment of PH concomitant with group I PH due to congenital heart disease is difficult, and the optimal pharmacotherapy is controversial. Intervention strategies for the left-sided atrioventricular valve in partial atrioventricular septal defect (AVSD) are problematic.

Case presentation

A 37-year-old woman who had undergone patch closure for a partial AVSD and mitral valve replacement with a rather large bioprosthesis at the juxta-annular position for mitral regurgitation 12 years earlier was referred to our institute because of severe PH. Echocardiography revealed calcification resulting in severe stenosis of the bioprosthesis and protrusion of its stent post into the left ventricular outflow tract; therefore, redo mitral valve replacement at the supra-annular position was performed using a mechanical valve. Combined group I and II PH gradually improved with meticulous postoperative medical management.

Conclusions

Severe PH due to stent post protrusion and structural valve deterioration in AVSD was successfully treated with redo mitral valve replacement. The present case was complicated with group I and II PH, for which medical therapy in conjunction with surgical treatment yielded an optimal therapeutic effect.
Lung abscess following ventilator-associated pneumonia during COVID-19: a retrospective multicenter cohort study
Authors: Hraiech S. , Ladjal K. , Guervilly C. , Hyvernat H. , Papazian L. , Forel J. M. , Lopez A. , Peres N. , Dellamonica J. , Leone M. , Gragueb-Chatti I.
Published: October 2023

Background

Patients undergoing mechanical ventilation (MV) for COVID-19 exhibit an increased risk of ventilator-associated pneumonia (VAP). The occurrence of lung abscesses following VAP in these patients has been poorly studied. We aimed to describe the incidence, characteristics, risk factors and prognosis of lung abscesses complicating VAP after COVID-19.

Methods

We conducted an observational, retrospective study in three French intensive care units. Patients admitted for acute respiratory failure with a confirmed SARS-CoV-2 PCR and requiring MV for more than 48 h were included.

Results

Among the 507 patients included, 326 (64%) had a documented VAP. Of these, 23 (7%) developed a lung abscess. Enterobacterales (15/23, 65%) were the main documentation, followed by non-fermenting Gram-negative bacilli (10/23, 43%) and Gram-positive cocci (8/23, 35%). Lung abscesses were mainly plurimicrobial (15/23, 65%). In multivariate analysis, a plurimicrobial 1st VAP episode (OR (95% CI) 2.93 (1.16–7.51); p = 0.02) and the use of hydrocortisone (OR (95% CI) 4.86 (1.95–12.1); p = 0.001) were associated with lung abscess development. Intensive care unit (ICU) mortality of patients with lung abscesses reached 52%, but was not significantly higher than for patients with VAP but no lung abscess. Patients with lung abscesses had reduced ventilator-free days at day 60, a longer duration of MV and ICU stay than patients with VAP but no lung abscess (respectively, 0 (0–3) vs. 16 (0–42) days; p < 0.001, 49 (32–73) vs. 25 (11–41) days; p < 0.001, 52 (36–77) vs. 28 (16–47) days; p < 0.001).

Conclusions

Lung abscessing pneumonia is not uncommon among COVID-19 patients developing VAP. A plurimicrobial first VAP episode and the use of hydrocortisone are independently associated with this complication. In COVID-19 patients with persistent VAP, a chest CT scan investigating the evolution toward lung abscess should be considered.
Large sample size and nonlinear sparse models outline epistatic effects in inflammatory bowel disease
Authors: Verplaetse Nora , Passemiers Antoine , Arany Adam , Moreau Yves , Raimondi Daniele
Published: October 2023

Background

Despite clear evidence of nonlinear interactions in the molecular architecture of polygenic diseases, linear models have so far appeared optimal in genotype-to-phenotype modeling. A key bottleneck for such modeling is that genetic data intrinsically suffers from underdetermination ($$p \gg n$$

p
≫
n

). Millions of variants are present in each individual while the collection of large, homogeneous cohorts is hindered by phenotype incidence, sequencing cost, and batch effects.

Results

We demonstrate that when we provide enough training data and control the complexity of nonlinear models, a neural network outperforms additive approaches in whole exome sequencing-based inflammatory bowel disease case–control prediction. To do so, we propose a biologically meaningful sparsified neural network architecture, providing empirical evidence for positive and negative epistatic effects present in the inflammatory bowel disease pathogenesis.

Conclusions

In this paper, we show that underdetermination is likely a major driver for the apparent optimality of additive modeling in clinical genetics today.
Risk of subsequent lower respiratory tract infection (LRTI) after hospitalization for COVID-19 LRTI and non-COVID-19 LRTI: a retrospective cohort study
Authors: Bruxvoort Katia J. , Fischer Heidi , Lewnard Joseph A. , Hong Vennis X. , Pomichowski Magdalena , Grant Lindsay R. , Jódar Luis , Gessner Bradford D. , Tartof Sara Y.
Published: October 2023

Background

Respiratory pathogens, including SARS-CoV-2, can cause pulmonary structural damage and physiologic impairment, which may increase the risk of subsequent lower respiratory tract infections (LRTI). Prior hospitalization for any reason is a risk factor for LRTI, but data on the risk of subsequent new-onset LRTI following hospitalization for COVID-19 LRTI or non-COVID-19 LRTI are needed to inform strategies for immunizations targeting respiratory pathogens.

Methods

We conducted a retrospective cohort study at Kaiser Permanente Southern California (KPSC) among adults hospitalized from 3/1/2020 to 5/31/2022, excluding labor and delivery. We categorized individuals into 3 mutually exclusive baseline exposure groups: those hospitalized for COVID-19 LRTI, those hospitalized for non-COVID-19 LRTI, and those hospitalized for all other causes without LRTI or COVID-19 (“non-LRTI”). Following hospital discharge, patients were followed up for new-onset LRTI, beginning 30 antibiotic-free days after hospital discharge until 8/31/2022. We used multivariable cause-specific Cox regression with time-varying covariates to estimate hazard ratios (HR) of new-onset LRTI comparing those hospitalized for COVID-19 LRTI or non-COVID-19 LRTI to those hospitalized for non-LRTI, adjusting for demographic and clinical characteristics.

Results

The study included 22,417 individuals hospitalized for COVID-19 LRTI, 12,795 individuals hospitalized for non-COVID-19 LRTI, and 176,788 individuals hospitalized for non-LRTI. Individuals hospitalized for non-COVID-19 LRTI were older and had more comorbidities than those hospitalized for COVID-19 LRTI or non-LRTI. Incidence rates per 1,000 person-years (95% CI) of new-onset LRTI were 52.5 (51.4–53.6) among individuals hospitalized for COVID-19 LRTI, 253.5 (243.7–263.6) among those hospitalized for non-COVID-19 LRTI, and 52.5 (51.4–53.6) among those hospitalized for non-LRTI. The adjusted hazard of new-onset LRTI during follow-up was 20% higher among individuals hospitalized for COVID-19 LRTI (HR 1.20 [95% CI: 1.12–1.28]) and 301% higher among individuals hospitalized for non-COVID-19 LRTI (HR 3.01 [95% CI: 2.87–3.15]) compared to those hospitalized for non-LRTI.

Conclusion

The risk of new-onset LRTI following hospital discharge was high, particularly among those hospitalized for non-COVID-19 LRTI, but also for COVID-19 LRTI. These data suggest that immunizations targeting respiratory pathogens, including COVID-19, should be considered for adults hospitalized for LRTI prior to hospital discharge.
Attitude, Perceived Barriers, and Challenges Toward Implementing Resource-Appropriate Guidelines for Hematologic Malignancies: Physicians' Survey in Ethiopia
Authors: Baissa Obsie T. , Hailu Workagegnehu , Tadesse Fisihatsion , Abubeker Abdulaziz , Aman Munir Awol , Fufa Diriba , Paltiel Ora
Published: October 2023

Limited awareness of harmonized guidelines among physicians while capacity is below par even for the basic strata.
High-Dose Methotrexate as CNS Prophylaxis in High-Risk Aggressive B-Cell Lymphoma
Authors: Lewis Katharine L. , Jakobsen Lasse H. , Villa Diego , Smedby Karin E. , Savage Kerry J. , Eyre Toby A. , Cwynarski Kate , Bishton Mark J. , Fox Christopher P. , Hawkes Eliza A. , Maurer Matthew J. , El-Galaly Tarec C. , Cheah Chan Y. ,   on behalf of the International CNS Prophylaxis Study Group, Bobillo Sabela , Caporn Paris L. , Van Zyl Joan , Klanova Magdalena , Trněny Marek , Puckrin Robert , Stewart Douglas A. , Tun Aung M. , Thanarajasingam Gita , Nair Ranjit , Nastoupil Loretta , Djebbari Faouzi , Joffe Erel , Eloranta Sandra , Harrysson Sara , Sehn Laurie H. , Maliske Seth M. , Poonsombudlert Kittika , Guo Xiao Y. , Hapgood Greg , Manos Kate , Khwaja Jahanzaib , Minson Adrian , Dickinson Michael , Øvlisen Andreas K. , Gregory Gareth P. , Gilbertson Michael , Streit Isaac T. , Scott Hamish W. , Ku Matthew , de Mel Sanjay , Ying Yong Kar , Xin Liu , Mokoonlall Mridula , Talaulikar Dipti , Hamad Nada , Srinivasan Sathia S. , McVilly Nicholas L. , Johnston Anna M. , Brunner Matthew J. , Pophali Priyanka A.
Published: October 2023

PURPOSE

CNS progression or relapse is an uncommon but devastating complication of aggressive B-cell lymphoma. There is no consensus regarding the optimal approach to CNS prophylaxis. This study was designed to determine whether high-dose methotrexate (HD-MTX) is effective at preventing CNS progression in patients at high risk of this complication.

PATIENTS AND METHODS

Patients age 18-80 years with aggressive B-cell lymphoma and high risk of CNS progression, treated with curative-intent anti–CD20-based chemoimmunotherapy, were included in this international, retrospective, observational study. Cause-specific hazard ratios (HRs) and cumulative risks of CNS progression were calculated according to use of HD-MTX, with time to CNS progression calculated from diagnosis for all patients (all-pts) and from completion of frontline systemic lymphoma induction therapy, for patients in complete response at completion of chemoimmunotherapy (CR-pts).

RESULTS

Two thousand four hundred eighteen all-pts (HD-MTX; n = 425) and 1,616 CR-pts (HD-MTX; n = 356) were included. CNS International Prognostic Index was 4-6 in 83.4% all-pts. Patients treated with HD-MTX had a lower risk of CNS progression (adjusted HR, 0.59 [95% CI, 0.38 to 0.90]; P = .014), but significance was not retained when confined to CR-pts (adjusted HR, 0.74 [95% CI, 0.42 to 1.30]; P = .29), with 5-year adjusted risk difference of 1.6% (95% CI, –1.5 to 4.4; all-pts) and 1.4% (95% CI, –1.5 to 4.1; CR-pts). Subgroups were underpowered to draw definitive conclusions regarding the efficacy of HD-MTX in individual high-risk clinical scenarios; however, there was no clear reduction in CNS progression risk with HD-MTX in any high-risk subgroup.

CONCLUSION

In this large study, high-risk patients receiving HD-MTX had a 7.2% 2-year risk of CNS progression, consistent with the progression risk in previously reported high-risk cohorts. Use of HD-MTX was not associated with a clinically meaningful reduction in risk of CNS progression.
Predictive Impact of RNF43 Mutations in Patients With Proficient Mismatch Repair/Microsatellite Stable BRAFV600E-Mutated Metastatic Colorectal Cancer Treated With Target Therapy or Chemotherapy
Authors: Moretto Roberto , Germani Marco Maria , Ros Javier , Daniel Francesca , Ghelardi Filippo , Vetere Guglielmo , Giordano Mirella , Toledo Rodrigo De Almeida , Bergamo Francesca , Randon Giovanni , Elez Elena , Lonardi Sara , Pietrantonio Filippo , Vignali Paola , Rossini Daniele , Matito Judit , Ugolini Clara , Fontanini Gabriella , Masi Gianluca , Cremolini Chiara
Published: October 2023

2nd-line target therapy outperforms chemotherapy in patients with BRAFV600E-mut mCRC regardless of RNF43 status.
Mast Cell Dynamics in the Ovary Are Governed by GnRH and Prolactin
Authors: Laoharatchatathanin Titaree , Rieanrakwong Duangjai , Hatsugai Yoshinori , Terashima Ryota , Yonezawa Tomohiro , Kurusu Shiro , Kawaminami Mitsumori
Published: October 2023

Gonadotrophin releasing hormone (GnRH) facilitates the migration of mast cells (MCs) into the involuting mammary gland. As GnRH is also expressed in the ovary, we examined changes in ovarian MCs. MCs in the ovary were mainly in interstitial tissue and their number increased during the estrous cycle to produce 2 peaks, one at diestrus 2 (20:00 hours) and another at proestrus (17:00 hours). Laser microdissection demonstrated that GnRH mRNA is expressed throughout ovarian tissues (corpora lutea, follicles, and interstitial tissues). GnRH immunoreactivity was also ubiquitous, but MCs were the most strongly immunostained. Analysis of GnRH mRNA in the ovary showed it to fluctuate similarly to the variation in MC number during the estrous cycle, and MCs also expressed GnRH. Local administration of a GnRH agonist (GnRHa) into the hemilateral ovarian bursa increased MCs in the administered ovary. MC number and GnRH mRNA were significantly lowered in the pregnant ovary. Prolactin administration suppressed the normal peaks in MC number in the ovary at both diestrus and proestrus. By contrast, a dopamine agonist, administered when prolactin was elevated during pseudopregnancy, increased ovarian MC number. Furthermore, prolactin inhibited GnRHa-induced peritoneal MC migration in a Transwell assay. These data clearly demonstrate that ovarian MC number is regulated positively by local GnRH expression and negatively by prolactin. The suppressive effect of prolactin on GnRH and MCs would be part of its luteotrophic action.
FRI001 Tanycytic Thyroid-stimulating Hormone Receptor Activation Increases Blood-Hypothalamus Barrier Permeability And Induces Appetite In Female Mice
Authors: Kannangara Hasni Suhasha , Jocoll Burgess , Miyashita Sari , Gumerova Anisa , Korkmaz Funda , Witztum Ronit , Sims Steven , Cheliadinova Uliana , Pevnev Georgii , Moldavski Ofer , Frolinger Tal , Yuen Tony , Ryu Vitaly , Zaidi Mone
Published: October 2023

Disclosure: H.S. Kannangara: None. B. Jocoll: None. S. Miyashita: None. A. Gumerova: None. F. Korkmaz: None. R. Witztum: None. S. Sims: None. U. Cheliadinova: None. G. Pevnev: None. O. Moldavski: None. T. Frolinger: None. T. Yuen: None. V. Ryu: None. M. Zaidi: None.

In addition to its well-known action to trigger thyroid hormone production, thyroid-stimulating hormone (TSH) is released in the brain, and its receptor (TSHR) has been found in brain sites, including the tanycytes of the third ventricle, that regulate ingestive behavior and convey metabolic information across the blood-hypothalamus barrier (BHB). Our recent work highlights largely undiscovered role for TSHRs in the tanycytes. Here, we tested the hypothesis that tanycytic TSHR activation triggers rapid remodeling of BHB vascular permeability inducing appetite. We compared hypothalamic vascular permeability of food deprived (FD) and ad libitum fed (AL) Tshr+/- and their wild type (WT) counterparts exploiting transmission electron microscopy studies and immunofluorescence for constitutive tight junction protein Claudin-1 and homodimer glycoprotein MECA-32, primarily expressed in tanycytes and endothelial cells, respectively. Fasting significantly increased the organization of tanycytic honeycomb pattern of Claudin-1 and fenestral MECA-32-associated diaphragms in the median eminence and arcuate nucleus implying decreased BHB vascular permeability in Tshr+/- mice. Transmission electron microscopy confirmed immunofluorescence results. In a separate gain-of-function experiment, TSHR activation by the small molecule MS438 increased BHB vascular permeability as evidenced by decreased Claudin-1 and MECA-32 immunostaining. Tanycytic TSHR activation significantly increased both food foraging and intake as during one-hour refeeding after FD. Surprisingly, refeeding restored neuronal activation marker c-Fos expression in the paraventricular nucleus of the hypothalamus, parabrachial nucleus and nucleus of the solitary tract, though failed to do so in the paraventricular nucleus and nucleus of the solitary tract of MS438-injected mice. Collectively, these data infer that modulation of tanycytic TSHRs plays an important role in BHB plasticity in relation with ingestive behavior.

Presentation: Friday, June 16, 2023
FRI009 Microbiome Affects Host Metabolic Homeostasis Via Differential Regulation Of Gene Expression In The Endocrine System
Authors: Milhouse Wynne , Ren Hongxia
Published: October 2023

Disclosure: W. Milhouse: None. H. Ren: None.

Dysbiosis has been implicated in many metabolic disorders, but the exact role of microbiota is not completely understood. To address this question, we used germ-free (GF) and conventional (CON) mouse models to examine the expression of genes critical for endocrine regulation of metabolic homeostasis. Samples of the mediobasal hypothalamus (MBH) were obtained from 18 germ-free and 18 conventional C57BL/6 mice (n=9 males, 9 females). Each gene transcript was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). We also collected the serum from both cohorts and measured ad libitum insulin and leptin concentrations by enzyme-linked immunosorbent assay (ELISA). Our results showed that, in the MBH, GF mice had increased expression of neuropeptides involved in feeding regulation, i.e., Neuropeptide Y (Npy) and Proopiomelanocortin (Pomc), compared to CON mice (p < 0.0001). Furthermore, CON mice had increased expression of a negative regulator of leptin signaling, Suppressor of cytokine signaling 3 (Socs3), in the MBH. Consistently, serum leptin in CON male mice was higher than that of male GF mice (p < 0.001). In the gut samples, the GF cohort demonstrated increased expression of gut hormones that promote satiety, such as Peptide yy (Pyy) and Cholecystokinin (Cck), respectively (p < 0.05 and p < 0.0001). The absence of a microbiome had differing effects on the expression of incretin hormones and the G protein-coupled receptors (GPCRs) that stimulate their secretion. In the jejunum, ileum, and colon of CON mice, expression of Glucagon-like peptide 1 (Glp-1) was increased compared to that of GF mice (p < 0.001, p < 0.05, and p < 0.0001, respectively). Conversely, Glucose-dependent insulinotropic polypeptide (Gip) showed increased expression in the duodenum of male and female GF mice (p < 0.0001). G protein-coupled receptor 119 (Gpr119) and G protein-coupled receptor 120 (Gpr120) showed increased expression only in the colon of female GF mice (p < 0.0001 and p < 0.01, respectively). Germ-free and conventional mice demonstrated comparable ad libitum insulin concentrations. We conclude that the increased expression of Pomc, Gip, Cck, and Pyy and the increased leptin sensitivity in GF mice contribute to the lean phenotype observed in these mice. The additional increase in Npy and decrease in Glp-1 likely play a compensatory role in regulating energy consumption and expenditure. Thus, the microbiome may impinge upon diverse effectors of the neuroendocrine and enteroendocrine systems to regulate host metabolism, influencing energy consumption and expenditure in the development of obesity.

Presentation: Friday, June 16, 2023
FRI031 A Novel Strategy To Detect Leptin Receptor (Lepr, fa) Mutation In Obesity And Diabetic Animal Model (Zucker Rats)
Authors: Xu Xinyun , Hu Xinge , Ma Guodong , Wang Tiannan , Wang Jayne , Chen Guoxun , Zhao Ling , Chen Jiangang
Published: October 2023

Disclosure: X. Xu: None. X. Hu: None. G. Ma: None. T. Wang: None. J. Wang: None. G. Chen: None. L. Zhao: None. J. Chen: None.

Globally, diabetes is among the leading causes of premature morbidity and mortality. Early intervention is crucial to achieve optimal outcomes and minimize the burden of diabetes. Animal models are indispensable tools to investigate etiology and explore novel strategies for diabetes treatment and prevention. Zucker strain and its derivatives, Zucker Fatty (ZF) and Zucker Diabetic Fatty (ZDF) rats, are one of the most used rodent models to study diabetes and diabetes-associated metabolic disorders. Homozygous Zucker rats with leptin receptor gene mutation (Lepr, fa-/-) spontaneously develop obesity, hypercholesterolemia, and hyperlipidemia. The wildtype (fa+/+) and heterozygous (fa+/-) littermates phenotypically are indistinguishable. Furthermore, early stages of diabetes are asymptomatic, and the obese phenotype is not appreciable in homogenous (fa-/-) Zucker rats until week 4 of age. Therefore, a rapid, cost-effective, and reliable genotyping method is essential to differentiate homozygous (fa-/-) rats from either wildtype (fa+/+) or heterozygotes (fa+/-) in early interventional studies. We reported a tetra-primer Amplification-Refractory Mutation System (ARMS)—PCR approach to detect leptin receptor fa mutation using genome DNA collected from ear and tail tissues of Zucker rats. Three different types of amplicon patterns are easily identified by agarose gel electrophoresis. Wildtype (fa+/+) genotype displays a 401 bp and a 201 bp amplicon band; heterozygous (fa+/-) consists of a 401 bp, a 263 bp, and a 201 bp amplicon band on the gel; homozygous (fa-/-) comes up with two bands of 401 bp and 263 bp. The genotypes identified by our tetra-primer ARMS—PCR method are further confirmed by sequence analysis. This method requires neither DNA purification nor restriction enzyme digestion, which is suitable for research exploring gene-environment interaction, as well as implementing appropriate intervention approaches in the research areas of diabetes and metabolic diseases.

Presentation: Friday, June 16, 2023
FRI051 Lean Mass And Fat Mass Across Different Age Groups In The Thai Population
Authors: Charoenngam Nipith , Theerakulpisut Daris , Sribenjalak Dueanchonnee , Pongchaiyakul Chatlert
Published: October 2023

Disclosure: N. Charoenngam: None. D. Theerakulpisut: None. D. Sribenjalak: None. C. Pongchaiyakul: None.

Introduction: Lean mass and fat mass have been shown to influence the risks of cardio-metabolic disorders. While obesity is defined as body mass index (BMI) of more than 30 kg/m2 in White, Hispanic, and Black individuals and 25 kg/m2 in Asian individuals, the cut-off values for lean mass and fat mass in different populations are less well-defined as data on reference values of lean mass (LM) and fat mass (FM), especially in the Southeast Asians, are limited. In this study, we aimed to determine the normative values of LM and FM across different age groups in the Thai population. Methods: Male and female consecutive community-dwelling individuals aged 20 - 90 years were recruited from Srinagarind Hospital, Khon Kaen, Thailand between 2010 and 2015. LM and FM were measured using dual energy x-ray absorptiometry on a Lunar Prodigy bone densitometer (GE Healthcare, Madison, WI). Lean mass index (LMI) and fat mass index (FMI) were calculated [LMI = LM (kg)/height (m)2, FMI = FM (kg)/height (m)2]. Percentiles of each variable stratified by age and sex were calculated. SPSS version 27 (SPSS Inc., Chicago, IL) was used to perform statistical analysis. Results: A total of 832 individuals (334 males and 498 females) were included in the study. The mean ± SD age, LM, FM, LMI and FMI were 50.0 ± 16.2 years, 38.9 ± 8.0 kg, 15.5 ± 7.7 kg, 15.6 ± 2.3 kg/m2 and 6.4 ± 3.3 kg/m2, respectively. In males, the median LM decreased from with age from 49.4 kg in 20 - 29 years group to 42.3 kg in ≥70 years group. The median LMI was relatively unchanged from age 20 - 59 years at 17.7 - 18.0 kg/m2 and dropped to 16.4 kg/m2 in ≥70 years group. The median FM and FMI increased with age from 6.3 kg and 2.5 kg/m2 in 20 - 29 years group to 11.9 kg and 4.6 kg/m2 in 60 - 69 years group and dropped to 10.3 kg and 4.1 kg/m2 in ≥70 years group. In females, the median LM peaked at age 30 - 39 years at 34.6 kg and decreased with age to 30.8 kg in ≥70 years group. The median LMI peaked at age 40 - 49 years at 14.6 kg/m2 and decreased with age to 13.8 kg/m2 in ≥70 years group. The median FM and FMI peaked at age 50 - 59 years at 20.7 kg and 9.0 kg/m2 and decreased with age to 15.9 kg and 7.1 kg/m2 in ≥70 years group. Conclusion: We generated age-stratified normative values of LM, FM, LMI and FMI from the cross-sectional data of community-dwelling Thai individuals. We observed that LM achieved its peak during early adulthood (age 20 - 29 years in males and 30 - 39 years in females) and decreased with older age. On the other hand, an inverse-U shaped association between FM and age was observed as FM achieved its peak at age 60 - 69 years in males and 50 - 59 in females and decreased with older age.

Presentation: Friday, June 16, 2023
FRI060 Real World Experience Of Weight Management In Low Socioeconomic Community Clinic
Authors: West Brittany Ann , Mon Sann
Published: October 2023

Disclosure: B.A. West: None. S. Mon: None.

Pilot Study: Real-world experience of weight management in low socioeconomic community clinic

Introduction: Management of obesity and unhealthy behaviors is an essential step in patients with Prediabetes and T2DM, particularly those with socioeconomic status (SES) in whom obesity is more prevalent. While several behavior interventions targeting obesity exist, a successful adaptation of interventions in routine care is challenging especially in those with low SES. We examined the real word experience of weight loss management in our community clinic. Method: Retrospective chart review of consecutive patients seen in an endocrinology clinic at a hospital-based community clinic. Result: A total of 23 female patients, average age 48.4 ± 10.8 years, with average BMI 37.4 ± 6.9 kg/m2, were provided comprehensive lifestyle counseling focusing on nutrition, exercise, sleep health at each visits along with semaglutide at the highest tolerable dose of 2.4 mg/dl weekly. Within 6 months from the initiation of semaglutide and the weight loss intervention, 11/23 (48%) patients lost weight by >5% from their baseline visit, and 17/20 (85%) patients at the end of 1 year. 12/20 (60%) and 6/20 (30%) lost weight at least by 10% and 15% respectively at the end of 1 year. Compared to the baseline data, weight ( 101.2±18.4) kg, SBP 127.6 ± 13.4 mmHg, HbA1C 6.0 ± 1.1 mg/dL, Total Cholesterol 182.1 ± 40.4 mg/dL, LDL 102.4 ± 35.8 mg/dL, most parameters were improved at the end of 6 and 12 months respectively: weight 91.0± 18.6 vs 88.4± 16.2 kg, SBP 125.2± 16.8 vs. 126.9± 15.6 mmHg, HbA1C 5.8 ± 1.2 vs 6.3 ± 1.4 mg/dl, Total cholesterol 178.9± 33.1 vs 175.0 ± 50.7mg/dl, LDL 100.4± 27.7 vs 101.8± 47.7 mg/dL. Conclusion: This real-world implementation study reported the benefits of weight loss and other clinical parameters after the intervention consisting of a combined health behavior counseling and use of semaglutide at the low-SES community clinic.

Presentation: Friday, June 16, 2023
FRI072 Biomechanical CT To Assess Bone After Sleeve Gastrectomy In Adolescents With Obesity- Prospective Longitudinal Study
Authors: Singhal Vibha , Huber Florian A , Tuli Shubhangi , Bouxsein Mary , Misra Madhusmita , Bredella Miriam A
Published: October 2023

Disclosure: V. Singhal: None. F.A. Huber: None. S. Tuli: None. M. Bouxsein: None. M. Misra: None. M.A. Bredella: None.

Background and Objective: Sleeve gastrectomy (SG) is effective in treating cardiometabolic complications of obesity but is associated with bone loss. Our aim was to determine the effect of SG on the lumbar spine by biomechanical computed tomography (CT) analysis in adolescents/young adults with obesity. We hypothesized that SG would lead to a decrease in strength and BMD compared to non-surgical controls. Methods: 12-month prospective non-randomized study of adolescents/young adults with obesity who either underwent SG (N=29) or were followed without surgery (controls, N=30). At baseline and 12 months, participants underwent QCT of L1 and L2 for biomechanical assessment and MRI of the abdomen and mid-thigh for body composition assessment. 12-month changes between groups were compared using Student’s t-test, and changes within groups were assessed using paired t-tests. Analyses were controlled for baseline and 12-month changes in BMI by multivariable analyses. Regression analysis was performed to evaluate the effect of body composition on bone parameters. Results: Participants in the SG group had a higher baseline BMI than controls (p=0.01) and lost an average of 34.3±13.6 kg 12 months after surgery, whereas weight was unchanged in controls (p<0.001). There were significant reductions in abdominal adipose tissue and thigh muscle area in the SG group compared to controls (p<0.001). Significant decreases in bone strength [-609 (-928, -291) vs. 103 (-173, 380) N], bending stiffness (-0.08 ± 0.16 vs. 0.07 ± 0.15 kNm/rad), average vBMD (-12 ± 12 vs. 0 ± 13 mg/cm3) and trabecular vBMD (-15 ± 13 vs. 2 ± 13 mg/cm³) were noted in the SG vs. control groups (all p<0.001). After controlling for change in BMI, a 12-month reduction in cortical BMD was significant in the SG group compared to controls (p=0.02). Reductions in strength and trabecular BMD were associated with reductions in BMI, visceral adipose tissue, and muscle (p≤0.03). Conclusion: Adolescents undergoing SG had a decrease in strength and volumetric BMD of the lumbar spine compared to non-surgical controls; reductions in cortical BMD were independent of weight reductions over the study duration. These changes were associated with a decrease in visceral fat and muscle mass.

Presentation: Friday, June 16, 2023
SAT161 The Impact Of A Very Low-calorie Diet On Reversal Of Metabolic Disorders Among Indian Subjects: A Real World Clinic-based Study
Authors: Deshpande Neeta , Kapoor Nitin
Published: October 2023

Disclosure: N. Deshpande: None. N. Kapoor: None.

Introduction: Reversal/remission of diabetes has been tested and well proven in the Caucasians. However, the Asian Indian phenotype is genetically and clinically distinct and there is a lack of robust data on this subject. Also, hitherto, the benefits of such an intervention have been reported only in a tightly monitored trial-based environment, but its efficacy from real-world data in busy clinical practices is lacking from the Indian subcontinent. In this study we aimed to study the impact of marked reduction of calorie intake on obesity indicators and diabetes related comorbidities in subjects of Indian ethnicity in a clinic-based cohort. Material and Methods: A 3-month structured Reversal Diet of 800-830 calories/day, comprising an inhouse packed commercially available meal replacement liquid formula, along with non-starchy veggies/soups/ diluted buttermilk, and fat replaced all 3 major meals. Clinical and biochemical metabolic parameters were assessed at baseline and at 3 months. Only those subjects who completed the 3-month assessment were included. Body composition was analyzed using bioimpedance with the INBODY 230 Analyser. Statistical analysis was undertaken using the SPSS 16·0 software package. This study was approved by the Institutional Review Board. Results: 374 subjects were included of which 117(31.2%) had type 2 Diabetes (T2DM). At baseline the mean (SD) age of the participants was 40.1(12.4) years and 333/374(89.1%) participants were women. There was significant improvement in body weight (85.4 Vs 77.7 Kg), BMI (32.6 Vs 29.8 kg/m2), Waist circumference (103.6 Vs 98.3 cm) and hip circumference (109.2 Vs 103.8 cm) at 3 months, compared to baseline. Body fat % changed from 41.9 to 37.6 and other anthropometric indicators (neck circumference, thigh circumference and arm circumference) were also significantly better after the intervention (P< .001). Among subjects with T2DM (31.2%), 40% had remission in diabetes, 28% of insulin users stopped insulin and about 30% stopped oral anti diabetic agents. Even among those who did not go into diabetes remission, Insulin was stopped in 29% and reduced in 38%, Oral Anti Diabetic agents reduced in 22%, blood pressure was normalized without medicines in 14% and NAFLD remission was attained in 41% of patients. Conclusion: A significant impact towards reversal of metabolic disorders was observed following a structured very low-calorie diet intervention, in this clinic-based cohort. Further follow-up studies are currently needed to provide long term evidence on the sustainability and long-term efficacy of such an intervention in the metabolically unique Indian population.

Presentation: Saturday, June 17, 2023
SAT653 Conditional Knockout Of Neural Sarm1 Improves Body Mass And Metabolic Health With High Fat Diet
Authors: Dabill Lila , Shen Ivana , Zhang Xiao , DiAntonio Aaron , Scheller Erica
Published: October 2023

Disclosure: L. Dabill: None. I. Shen: None. X. Zhang: None. A. DiAntonio: None. E. Scheller: None.

Sterile alpha and TIR motif containing 1 (Sarm1) is a toll-like receptor, highly expressed in the nervous system, that is activated with injury, inflammation, and oxidative stress to promote axon degeneration and dysfunction. Previous findings with global knockout of Sarm1 showed evidence of metabolic improvements in high-fat diet (HFD) induced type 2 diabetes (T2D) as well as reduced peripheral axon degeneration. We hypothesize that this is due to the actions of Sarm1 in the nervous system. To test this hypothesis, we used Baf53b-Cre to knock out Sarm1 in all neurons throughout the body (Sarm1-cKO). Both control and Sarm1-cKO mice were fed HFD for 24 weeks, starting at 4-6 weeks of age. Quantitative PCR (qPCR) analysis confirmed high Sarm1 expression in the dorsal root ganglia (DRG) with a significant decrease in Sarm1-cKO mice; no significant difference in Sarm1 expression was observed in bone, testis, liver, iWAT, or brain tissue between control and Sarm1-cKO mice. Over the 24-week study period, Sarm1-cKO mice fed HFD gained 20% less body mass than controls (20.8g mass gain on average in cKO vs 26g mass gain in control mice). Furthermore, subcutaneous inguinal fat, but not visceral gonadal fat, was preferentially reduced by 26% in Sarm1-cKO mice. Sarm1-cKO mice on HFD also showed evidence of metabolic rescue with smaller livers and less steatosis. Lastly, insulin tolerance testing (ITT) results suggest that Sarm1-cKO mice on HFD were more sensitive to insulin than controls. Sarm1 inhibitors are currently under clinical development for the treatment of neurodegenerative disease. These results show that inhibition of Sarm1-dependent neurometabolic regulatory pathways also has the potential to support metabolic health in settings of obesity and T2D.

Presentation: Saturday, June 17, 2023
SAT146 Recurrent Hypoglycemia Following Asparaginase Therapy For Childhood Cancer: Institutional Experience
Authors: Tantoush Manal
Published: October 2023

Disclosure: M. Tantoush: None.

Background: Asparaginase (ASP) is a cornerstone pediatric leukemia and lymphoma therapy. Hyperglycemia following ASP is described, but hypoglycemia is infrequently identified as a complication. Following hypoglycemic events in children receiving ASP therapy, evaluation of associations and outcomes was undertaken. Aim: Evaluate and describe the risk factors, prevalence, duration, severity, recurrence and outcomes of children developing ASP-induced hypoglycemia. Method: Retrospective cohort study using electronic medical records to identify all patients who received ASP (PEGylated or non-PEGylated), and had diagnosis of hypoglycemia between 6/1/2017 and 6/30/22 at Texas Children's Hospital. We defined ASP-induced hypoglycemia as blood glucose (BG) <70 mg/dl 2-8 weeks from ASP administration, without alternative causes. If hypoglycemia evaluation was completed, hyperinsulinism was defined by: BG < 50 mg/dL; insulin > 2 mIU/mL; β-hydroxybutyrate < 1.8 mmol/L; free fatty acids < 1.7 mmol/L; or a post-glucagon BG > 30 mg/dL. Demographic and clinically relevant data were collected. Descriptive analysis was completed. Univariate regression models using Stata16 were analyzed. A p-value <0.05 was statistically significant. Results: Patients receiving ASP totaled 722, with 56 (7.6%) having ASP-induced hypoglycemia. Cancer diagnosis included acute lymphoblastic leukemia (n=50), lymphoblastic lymphoma (n=5) or acute myeloid leukemia (n=1). Median age was 4.4 years (IQR: 2.6 - 8.1), with 46% Hispanic and 59% male. Median BMI z-score was +0.4 (IQR: -0.3 - 1.2). Initial hypoglycemia event was during Induction therapy in 86% (n=48), with median time from ASP to hypoglycemia diagnosis 11 days (IQR: 6-15). Median lowest BG was 51 mg/dL (IQR: 43-57) with median duration 11 days (IQR: 7-19). Treatment included dietary change (52%, n=29), cornstarch (29%, n=16), and continuous feedings (13%, n=7). Continuous BG monitoring was utilized in 9 (16%). A critical sample was obtained in 18 (32%) with all evaluations consistent with hyperinsulinism. Recurrent hypoglycemia with subsequent ASP doses occurred in 42 (74%), with a median duration 14 days (IQR: 8-21; max: 56 days). Overall cancer survival following ASP-induced hypoglycemia was 80% (85% if excluding relapse disease), with 3 years’ median follow up. Severity of hypoglycemia (lowest BG, number of events, or length of events) was not associated with age, sex, ethnicity, or BMI z-score in univariate analysis. Conclusion: ASP-induced hypoglycemia is relatively common, often recurs with subsequent dosing, and may become severe requiring intensive therapy. Prospective screening of patients receiving ASP may be appropriate to prevent and manage events. Patients completed chemotherapy without change in survival at 3 years’ follow-up. Further studies to elucidate prognostic factors of ASP-induced hypoglycemia are needed.

Presentation: Saturday, June 17, 2023
SAT147 A Pharmacist Driven Active Surveillance Program To Reduce Hypoglycemic Recurrences In The Inpatient Setting
Authors: Kim Steve , Tran Hai , Gianchandani Roma Yogesh
Published: October 2023

Disclosure: S. Kim: None. H. Tran: None. R.Y. Gianchandani: None.

Background: Hyper and hypoglycemia increase morbidity and mortality in hospitalized patients. Glucose excursions are time sensitive and require timely response to prevent future episodes of dysglycemia. As part of a quality improvement initiative, we implemented an Active Glycemic Surveillance (AGS) program in July 2022 targeting patients with hypoglycemia (BG <70 mg/dL) based on a preliminary evaluation that revealed recurrent hypoglycemia was an opportunity for improvement. Pharmacist involvement in glycemic management has been shown to improve clinical outcomes in the acute care setting. Our AGS program is unique in that pharmacist trained in inpatient glycemic management is empowered to directly intervene on antihyperglycemic medication orders under scope of practice by a protocol approved through the pharmacy and therapeutics committee.

Intervention: The AGS team consists of an endocrinologist and a diabetes stewardship pharmacist. A policy was developed and approved by P and T that outlines the types of interventions and orders that the diabetes stewardship pharmacist is able to make under scope of practice. These interventions include the ability to order certain labs (POCT BG, HgbA1C), and to adjust or discontinue certain anti-hyperglycemic agents Hospitalized patients who have a BG <70 mg/dL in the last 24 hours are reviewed by the AGS team. Chart review is performed on each patient to identify contributing factors and complicated cases are discussed with the endocrinologist prior to contacting the providers or making changes to orders. Providers are given rationale for changes as well as any other recommendations related to glycemic management. Results: During a 3 month period between August and October 2022, 848 cases of hypoglycemia were evaluated. Of these, 450 (53%) were found to be caused by an antihyperglycemic agent and 401 interventions were made by either the AGS team or other providers. The AGS team made 167 (41.6%) interventions and had a 24 h recurrence rate of 8.3% compared to 16.3% for all other providers. The most common types of interventions made by the AGS team were adjusting the insulin correction scale (78), basal insulin (57), bolus/meal insulin (16), oral medications (10), and TPN insulin (3). Conclusion: Our preliminary data show that a pharmacist-driven active surveillance program can reduce hypoglycemic recurrences. In the short time our AGS program has been implemented we have seen in increased utilization of appropriate correction scales, a decreased reliance on basal insulin or correction scale as the sole means of glycemic management, and an increase in endocrinology consultation for glycemic guidance. Future data will show the impact of this program on our overall hypoglycemia and hyperglycemia rates in future.

Presentation: Saturday, June 17, 2023
SAT150 "Sawtooth" Hypoglycemia: Rare Case Of IGF-2 Mediated Hypoglycemia With Elevated Proinsulin Level And "Sawtooth" Pattern On CGMS
Authors: Goparaju Pruthvi , Zena Mohsen
Published: October 2023

Disclosure: P. Goparaju: None. M. Zena: None.

Background: IGF-2 mediated hypoglycemia is usually associated with low Insulin, C-peptide and Proinsulin levels. We present an extremely rare case of IGF-2 mediated hypoglycemia with elevated Proinsulin level and an unusual “saw tooth” pattern on Continuous glucose monitoring system(CGMS). Clinical Case: 53-year-old male with history of metastatic Liposarcoma was admitted to the hospital with severe hypoglycemia. Whipple’s triad was positive on presentation, patient had symptoms of altered sensorium, blood glucose of 24 mg/dl, and symptoms improved upon correction of hypoglycemia. The patient was admitted to the ICU and IV dextrose was initiated.As Liposarcomas are known to be associated with Non-islet cell tumor hypoglycemia (NICTH), treatment with Prednisone was started. Prior to this, initial hypoglycemia workup was sent when blood sample was drawn during a hypoglycemia episode. Patient has no personal or family history of Diabetes. Adrenal insufficiency was ruled out with morning cortisol of 17.8 ug/dl. Serum glucose was low at 40mg/dl, Insulin<1(0-17 pmol/L), C-peptide level low at 0.4 (0.8-3.9 ng/ml), IGF-1 level was low at 68 (74-225 ng/ml), normal IGF-2 at 626 (333-967 ng/ml) and increased IGF-2/IGF-1 ratio of 9.2(Normally around 3:1). All the lab work above is consistent with IGF-2 mediated hypoglycemia with low Insulin, C-peptide and IGF-1 levels and increased IGF-2/IGF-1 ratio. Interestingly, he has an elevated Proinsulin level of 36.9 (0.0-10.0 pmol/L) which is very unusual.Prednisone was started at 20mg daily to which there was reasonable response, dose was eventually increased to 60mg daily before he was safely sent home. He was discharged on a CGMS and the data was downloaded 2 weeks later. He had an interesting “Saw tooth” pattern of glycemia on the daily glucose graphs. As the patient had access to live data, he was trying to correct the falling blood glucose which briefly improved the readings but was quickly followed by another drop and this sequence carried on leading to a unique blood glucose pattern on the CGMS. Conclusion: Proinsulin level is usually suppressed in IGF-2 mediated hypoglycemia. Our case is unusually associated with high Proinsulin level. One hypothesis is the possible structural similarities leading to lab assay interactions between Proinsulin and “Pro-IGF-2”, which is thought to be one of the main molecules responsible for hypoglycemia in this condition. More studies in future will be helpful to study this possible association. Our case also had a remarkable “Saw tooth” pattern on CGMS glucose graphs which is very rarely seen in clinical practice.

References: Dynkevich, Yevgeniya et al. “Tumors, IGF-2, and hypoglycemia: insights from the clinic, the laboratory, and the historical archive.” Endocrine reviews vol. 34,6 (2013): 798-826. doi:10.1210/er.2012-1033

Presentation: Saturday, June 17, 2023