Studies occasionally demonstrate various ethnic disparities regarding differentiated thyroid cancer (DTC) characteristics and outcomes. The impact of public health care and close access to care has been studied scarcely. With a unique minority group within the hospital region, this case control study aims to investigate this further. A retrospective cohort study of patients with DTC diagnosis who followed-up at a tertiary medical center between 2013 and 2024. The patients were categorized into Minority (study group) or non-minority (control group) and were reviewed for DTC characteristics at presentation and outcomes including histopathology, risk of structural disease recurrence, response to initial treatment, and mortality and risk group according to the 2015 ATA guidelines [1]. A total of 316 patients were included, of whom 100 (31.6

We examined whether long-term exposure to visceral-adipose-tissue (VAT) influences brain atrophy and cognitive performance years after lifestyle intervention. In the Follow-Interventions-Trials (FIT) project, 533 adults (age=61.4 y, 86% men) from four prior 18-24-month lifestyle randomized-clinical-trials underwent abdominal/brain magnetic-resonance-imaging (MRI)s and Montreal-Cognitive-Assessment (MoCA) testing 5-16 y after interventions. Lower VAT exposure, calculated by area-under-the-curve, from baseline, post-intervention, and follow-up, independently resulted in higher MoCA scores. VAT loss during intervention predicted higher brain volumes at follow-up, independent of weight loss. Among participants with three brain and VAT MRI scans, lower long-term VAT was associated with a slower rate of brain atrophy. These patterns were not observed for deep/superficial subcutaneous-adipose-tissues. Improved glycemic control parameters, rather than lipid or inflammatory markers, were mostly related to the favorable longitudinal brain outcomes. This long-term, large-scale intervention and follow-up MRI study suggests that sustained visceral fat loss, rather than weight loss, is linked to better cognition and attenuation of brain atrophy years later, mainly via improved glycemic control. Trial registration: DIRECT (Clinical-trials-identifier: NCT00160108); CASCADE (Clinical-trials-identifier: NCT00784433); CENTRAL (Clinical-trials-identifier: NCT01530724); DIRECT-PLUS (Clinical-trials-identifier: NCT03020186).

BACKGROUND:During the 18-month CENTRAL (Effect of Weight-Loss Diet Strategies and Exercise on Dynamics of Body Fat Depots and Metabolic Rate) and DIRECT-PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed) randomized controlled trials, participants achieved considerable reductions in abdominal and ectopic fat. We examined the long-term postintervention cardiometabolic profile associated with these changes. METHODS:We invited participants from CENTRAL (2012-2014) and DIRECT-PLUS (2017-2018), which evaluated dietary patterns (low-fat, healthy dietary guidelines and Mediterranean diet variants, including standard, low-carbohydrate, and polyphenol-enriched "green" Mediterranean diets) combined with structured physical activity. Participants underwent additional magnetic resonance imaging of visceral adipose tissue, deep subcutaneous adipose tissue (SAT), superficial SAT, intrahepatic fat, and intrapancreatic fat, along with clinical follow-up measurements, 5 and 10 years after completion of the trials. RESULTS:We reached 366 out of 381 eligible participants (96%) for follow-up. Despite complete weight regain, waist circumference and abdominal fat depots, including visceral adipose tissue, deep SAT, and superficial SAT, partially preserved their intervention-induced achievements at long-term follow-up (false discovery rate ≤0.01 for all). In contrast, postintervention reductions of intrahepatic fat and intrapancreatic fat were fully and excessively gained during follow-up, respectively (false discovery rate ≤0.01 for both). Each 10% intervention-induced loss of visceral adipose tissue, superficial SAT, and intrapancreatic fat were associated with long-term postintervention improvements in Metabolic Score for Insulin Resistance, composite risk score, and Metabolic Syndrome Severity Score (meta-analysis models adjusted to weight change, Mediterranean diet adherence and physical activity scores at follow-up, and further measures; all P<0.05). Only 10% visceral adipose tissue loss, however, was independently associated with a 28% lower risk of incident type 2 diabetes (hazard ratio, 0.72 [95% CI, 0.54-0.94]; multivariable model) during follow-up. CONCLUSIONS:This 5- and 10-year follow-up of 18-month clinical trials suggests that diet and physical activity lifestyle interventions may yield long-term improvements in cardiometabolic measures despite weight regain. A 10% reduction in visceral fat due to lifestyle interventions may reduce future type 2 diabetes risk by nearly 30%. Visceral fat loss rather than weight loss emerges as a key target for durable cardiometabolic health. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01530724 and NCT03020186.

Abstract Weight cycling (WC), defined as weight gain, loss, and regain, is common in obesity, but its metabolic consequences remain unclear. We tested whether WC-aggravated glucose intolerance in obesity is age-dependent and linked to circadian disruption. Young (7w) and mid-aged (12m) mice underwent a 15-week dietary intervention: Lean and Obese mice fed normal chow (NC) and high-fat diet (HFD) throughout, respectively. WC mice undergone HFD-induced weight gain, NC-induced weight loss, and a second HFD-induced weight regain. Late-onset obese (LO) mice ate HFD only paralleling weight regain of WC. In young, but not mid-aged mice, prior obesity accelerated weight regain upon HFD re-exposure, and aggravated glucose intolerance beyond that observed in Obese mice. This occurred without a worse adipose inflammatory profile. Rather, WC young mice exhibited blunting of light/dark-phase oscillation of feeding and energy metabolism, adipose and hepatic core clock gene oscillation, and increased hepatic expression of clock and gluconeogenic genes during the inactive phase. Restricting food availability to the active phase did not alter final weight regain, but improved glucose tolerance selectively in WC mice, normalized hepatic gluconeogenic and clock-genes’ expression in both liver and adipose tissue. These findings identify circadian disruption as a modifiable mediator of the adverse metabolic impact of WC in young-adulthood obesity. Highlights Weight cycling is common in obesity, but whether it worsens metabolic dysfunction beyond persistent obesity remains unclear. We asked whether weight cycling aggravates glucose intolerance in an age-dependent manner and whether circadian disruption contributes to this effect. In young, but not mid-aged mice, weight cycling accelerated weight regain and worsened glucose intolerance, accompanied by blunted diurnal oscillation of behavioral parameters and core clock gene expression, without exaggerated adipose inflammation. Active-phase time-restricted feeding improved WC-induced aggravated glucose tolerance and circadian oscillation, identifying circadian disruption as a modifiable mechanism linking weight cycling adverse metabolic outcomes in young-adulthood obesity.

Context Female sex is a risk factor for differentiated thyroid carcinoma (DTC), potentially due to reproductive influences. However, data on the association between parity and DTC risk remain inconsistent. Objective To assess the association between parity and DTC risk in a high-multiparity population. Design Population-based case-control study (1982-2022). Setting A single tertiary medical center. Patients or Other Participants The study included 300 female patients with DTC and 900 controls, matched by birth year and ethnicity. The primary exposure was the number of deliveries before DTC diagnosis. Main Outcome Measure(s) Association between parity and DTC risk evaluated by logistic regression, adjusted for socioeconomic status, TSH levels, oral contraceptive use, and autoimmune thyroid diseases. Results The median age at DTC diagnosis was 39 years; 60% of participants were Jewish and 40% were Arab. Baseline characteristics were comparable, except for higher rates of autoimmune thyroid diseases in cases: Hashimoto thyroiditis (9.7% vs 1.8%, P < .001) and Graves’ disease (6.3% vs 2.7%, P = .005). Parity was associated with increased DTC risk starting at 4 deliveries (OR = 1.70, 95% CI: 1.051-2.741, P = .030), with the highest risk at 6 or more (odds ratio = 1.89; 95% CI, 1.052-3.393; P = .033). This association was largely driven by Arab women, who had significantly higher grand multiparity rates (62.6% vs 13.4%; median 5 vs 3 deliveries; P < .001). Conclusion High parity, primarily among Arab women, was associated with increased DTC risk, with significance observed at 4 or more deliveries.

Abstract Background Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10–25% of all MBS procedures and is commonly performed for recurrent weight gain after initial weight loss. How weight loss followed by regain reshapes adipose tissue biology remains unclear. We hypothesized that women undergoing r-BS exhibit a distinct adipose tissue signature compared with those undergoing primary bariatric surgery (p-BS). Methods We analyzed subcutaneous and visceral adipose tissues (SAT, VAT, respectively) from women undergoing either p-BS, or r-BS with documented, >15% weight-loss after prior MBS. Tissues were assessed histologically, molecularly, and functionally (activation of human microglia cells (HMC3) by SAT secretome). Results Consistent with other cohorts, women undergoing r-BS (n=21) trended to be older (47.2 vs. 40.5 y, p=0.06) than those undergoing p-BS (n=35), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters such as fasting insulin, CRP and HDL-c. Adipose tissues’ histological features (adipocyte size, fibrosis, macrophage and crown-like structures abundance) were similar, while adipose mast-cells were slightly (though insignificantly) more prevalent in r-BS. Single-nucleus RNA-seq-based deconvolution algorithm applied unto bulk RNA-seq to uncover differences in cell composition confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, it uncovered unique transcriptome of SAT, with activation of inflammatory pathways in r-BS. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFκB-regulated cytokines IL6 and IL8. Biological impact of the more inflammatory secretome was demonstrated by its increased ability to inflammatory activate human microglia cells. Conclusions Prior BS with significant weight-loss-regain in women is associated with inflammatory transcriptome and secretome of SAT, possibly reflecting on adipose-brain endocrine communication.

BackgroundThe COVID-19 pandemic has been associated with various autoimmune manifestations. Several studies have suggested a potential association between COVID-19 and thyroid diseases (TDs); however, findings remain inconclusive and are primarily based on relatively small studies. Population-level data examining the differential impact of the pandemic on specific thyroid conditions are scarce.ObjectiveTo examine the incidence patterns of Hashimoto’s Thyroiditis (HT), Graves’ Disease (GD), and Subacute Thyroiditis (SAT) during the COVID-19 pandemic compared to the pre-pandemic period.MethodsWe conducted a population-based retrospective cohort study using interrupted time series analysis of adults (≥16 years) in the Clalit Health Services southern district of Israel from January 2018 to December 2022. New cases of TDs were identified using either ICD-9 codes, laboratory results, medication dispensing data or a combination of them. Monthly disease-specific incidence rates were compared between pre-pandemic (January 2018-February 2020) and pandemic (March 2020-December 2022) periods, with adjustment for seasonal variations.ResultsAmong 4,765 incident TD cases identified, 3,731 (78.3%) had HT, 698 (14.6%) had GD, and 336 (7.1%) had SAT. The mean age was similar across groups (43–45 years) with consistent female predominance (77%). Interrupted time series analysis revealed a significant 30% increase in HT incidence during the pandemic period (IRR 1.30, 95% CI 1.04-1.64, p=0.023), which began prior to the national vaccination campaign. GD showed a non-significant upward trend suggestive of a possible increased incidence (IRR 1.66, 95% CI 0.99-2.79, p=0.054). Conversely, SAT demonstrated a significant 54% reduction in incidence (IRR 0.46, 95% CI 0.21-0.99, p=0.049).ConclusionsThe COVID-19 pandemic was associated with a significant increase in HT incidence and an unexpected decrease in SAT. These findings highlight the heterogeneous impact of the pandemic on different TDs.

It remains unclear whether reengaging in lifestyle weight loss interventions is effective for the long-term. We conducted the CENTRAL (trial 1, T1) lifestyle weight-loss trial in 2012–2014, and the DIRECT-PLUS (trial 2, T2) weight-loss trial in 2017–2018. All participants were invited for follow-up in 2022–2024 to assess weight, metabolic biomarkers, and fat depots via magnetic-resonance-imaging (MRI) five years after the second trial. The analysis included 572 trial observations contributed by 480 participants; of these, 388 participated in one of the two trials and 92 participated in both (T1 + T2 rejoiners). At follow-up, 384/480 (80

BACKGROUND:To assess the association between preconception hemithyroidectomy and the risk of gestational hypothyroidism and obstetric outcomes. METHODS:This nationwide population-based retrospective cohort study compared euthyroid pregnant women with a history of hemithyroidectomy prior to conception with age- and body mass index-matched (81 ratio) pregnant women with intact thyroid glands. Data were retrieved from a comprehensive integrated healthcare database. The primary outcome was overt gestational hypothyroidism (elevated thyrotropin [TSH] with low free T4). Secondary outcomes included thyroid hormone replacement therapy, obstetric complications, and the interval from surgery to the onset of overt hypothyroidism during pregnancy. RESULTS:A total of 521 pregnancies following hemithyroidectomy were compared with 4168 matched control pregnancies. Overt gestational hypothyroidism was significantly more frequent among women with prior hemithyroidectomy than among controls (22.5% vs. 1.9%, p < 0.001), and the risk was highest among those operated for thyroid cancer. Thyroid hormone replacement therapy during pregnancy was markedly higher in the hemithyroidectomy cohort (19% vs. 2.7%, p < 0.001). TSH levels exceeding 10 mIU/L occurred in 4.7% of exposed pregnancies compared with less than 0.1% of controls (p < 0.001). The median interval from surgery to gestational diagnosis was 2.5 years (interquartile range, 1.0-5.4 years), with nearly two-thirds of affected women already meeting biochemical criteria at their first prenatal assessment. Notably, a profound surveillance gap was uncovered 29.5% of post-hemithyroidectomy women completely missed first-trimester TSH screening. Despite the higher burden of biochemical thyroid dysfunction, absolute rates of adverse obstetric outcomes did not differ significantly between cohorts. CONCLUSIONS:Preconception hemithyroidectomy is associated with a markedly increased risk of gestational hypothyroidism and a higher need for thyroid hormone replacement, particularly in women treated for thyroid cancer. These findings support closer biochemical monitoring during pregnancy, in line with current guidelines. Despite this increased risk, obstetric outcomes were similar to those of women with intact thyroid glands.

While neuroinflammation is an established response to both weight gain and aging, the hypothalamic neuroinflammatory early response to weight loss (WL) remains unknown, particularly in mid-age. Here, we questioned whether WL-induced rapid restoration of normoglycemia is mediated by the resolution of hypothalamic microgliosis in mid-aged mice. Mid-aged (1 year) mice were fed normal chow (NC) or a high-fat diet (HFD, 8 weeks), and WL was induced by a 2-week switch back to NC. Key findings were compared to young (7 weeks) mice. Mid-aged WL mice lost within 2 weeks 54

Human adipose depots are functionally distinct. Yet, recent single-nucleus RNA sequencing (snRNA-seq) analyses largely uncovered overlapping or similar cell-type landscapes. We hypothesized that adipocyte subtypes, differentiation trajectories and/or intercellular communication patterns could illuminate this depot similarity–difference gap. For this, we performed snRNA-seq of human subcutaneous or visceral adipose tissues (five or ten samples, respectively). Of 27,665 adipocyte nuclei in both depots, most were ‘classical’, namely enriched in lipid metabolism pathways. However, we also observed ‘nonclassical’ adipocyte subtypes, enriched in immune-related, extracellular matrix deposition (fibrosis), vascularization or angiogenesis or ribosomal and mitochondrial processes. Pseudo-temporal analysis showed a developmental trajectory from adipose progenitor cells to classical adipocytes via nonclassical adipocytes, suggesting that the classical state stems from loss, rather than gain, of specialized functions. Last, intercellular communication routes were consistent with the different inflammatory tone of the two depots. Jointly, these findings provide a high-resolution view into the contribution of cellular composition, differentiation and intercellular communication patterns to human fat depot differences. Single-nucleus RNA sequencing of human visceral and subcutaneous adipose tissues is used to identify adipocyte subpopulations and explore their developmental trajectories and interactions.

Metastatic cervical lymph nodes (LN) are detected in 20-30% of patients with differentiated thyroid cancer (DTC). Current guidelines recommend that once a cervical LN is suspected to be DTC metastasis during a neck ultrasound (US) procedure, it should be investigated via a fine needle aspiration (FNA) biopsy for cytological evaluation and saline washout of the needle for thyroglobulin (Tg) measurement (FNA-Tg). Since Tg is a protein produced exclusively by thyroid follicular cells, a positive FNA-Tg result establishes the diagnosis of metastatic DTC irrespective of cytology. The conventional, immunoassay-based, FNA-Tg washout requires a laboratory and skilled personnel. We developed a semi-quantitative, lateral flow-based method which was shown to detect at the point-of-care (POC), within 10 minutes, positive Tg samples in needle washouts of a suspicious LN at the site of FNA biopsy. In the pre-clinical phase, the POC-Tg limit of detection was determined to be at a concentration equal to 5 ng/mL, after a 1 mL dilution with normal saline. Our prototype was optimized by evaluating different components: types of membranes, pads, antibodies, and gold conjugates. We evaluated our POC-Tg kits on thirty clinical samples: 16 were found positive while the other 14 were seen as negative. All the negative and positive results were further validated by the attending clinical labs, resulting in 100% compatibility compared to the standard procedure. The proof-of-value of our POC-Tg test lies in its ability to significantly reduce the time to results, thus enhancing clinical decision-making, and saving time and valuable resources. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Israel Innovation Authority [Kmin grant, number 64994], and the Israel Cancer Association [grant number 20230021]. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this study was obtained by the Helsinki committee of Soroka University Medical Center (SUMC), approval number 190-17-SOR. All patients provided written informed consent before the FNA procedure was initiated. Patients 18-year-old and older, able to understand and sign the informed consent form, who were evaluated for cervical LN suspected as DTC metastases, were offered to participate. Pregnant women were excluded. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

Objective: Obesity-induced-dysglycemia and hypothalamic-microgliosis coincide, but whether they remain linked upon obesity reversal, and what is the effect of age, remain unclear. Here we hypothesized that rapid normalization of dysglycemia upon obesity-reversal remains linked to microgliosis resolution, but differs between young and mid-aged mice. Methods: Young (7w) and mid-aged (1y) mice were fed normal chow (NC) or high-fat diet (HFD,8w), then switched to NC (Rev,2w). Results: Compared to young mice, NC-fed mid-aged mice were heavier and weight-stable, gained weight with HFD comparably, and lost less weight in Rev. HFD-induced dysglycemia was less severe in mid-aged compared to young mice, but similarly normalized by obesity-reversal. However, whole-hypothalamus RNA sequencing revealed 2,419 differentially expressed genes (DEGs) in mid-aged mice, ~4-times more than in young mice, and in both age-groups ~80% of DEGs obesity-induced changes were aggravated in Rev. Furthermore, compared with young mice, middle-aged mice showed greater obesity-induced microglial cyto-morphological changes in the arcuate nucleus (ARC), which associated with increased p-NFκB-(p-p65) nuclear staining. Only in middle-aged mice obesity-induced microglial changes were aggravated by obesity reversal, with cell volume correlating (Rho(ρ)=0.691, p=0.001) with adipose tissue crown-like-structures. Conclusions: In conclusion, rapid dysglycemia normalization is uncoupled to the resolution of hypothalamic microgliosis, more-so in mid-age. ### Competing Interest Statement The authors have declared no competing interest.

Background/Objectives: Overt hypothyroidism during pregnancy has been linked to adverse outcomes, including preterm birth, low birth weight, and impaired fetal neurocognitive development. This study aimed to evaluate pregnancy complications in women with overt hypothyroidism (TSH ≥ 10) through a cross-sectional study. Methods: Data from 259,897 live-birth pregnancies (2013-2022) from Clalit Health Services (CHS) were analyzed. The study included all CHS-insured women aged ≥ 18 years with available TSH results during pregnancy. Overt hypothyroidism was defined as a mean TSH ≥ 10 mIU/L, while the euthyroid reference group had TSH levels < 4 mIU/L and no history of hypothyroidism or levothyroxine use. Cases of overt hypothyroidism were matched with 15 controls using propensity score-based matching. Covariates included maternal age, ethnicity, socioeconomic status, IVF use, recurrent pregnancy loss, and smoking. Pregnancy complications were compared between groups using descriptive statistics and univariate analysis. A quasi-Poisson regression model was used to assess complication risk in overt hypothyroidism versus matched controls. Results: The final analysis included 9125 euthyroid and 611 overt hypothyroid pregnancies, with comparable baseline characteristics between groups. No significant differences were found in maternal age, ethnicity, socioeconomic scores, IVF rates, recurrent pregnancy loss, diabetes, smoking, gestational age at delivery, or rates of preterm birth, pre-eclampsia, gestational diabetes, cesarean section, and intrauterine growth restriction. Overall, overt hypothyroidism was not associated with increased complications. Sensitivity analyses using maximum TSH levels during pregnancy showed a slightly elevated risk for pregnancy complications (IRR 1.1, CI 1.04-1.18; p = 0.002). Conclusions: Overt hypothyroidism was not associated with an increased risk of adverse pregnancy outcomes when adjusted for confounding factors, suggesting that treatment decisions should be made on an individual basis.

INTRODUCTION:The definition of thyroid goiter remains ambiguous, yet size may impact both malignancy rate and surgical complications' rate. METHODS:All patients with thyroid goiter who underwent thyroidectomy between 1/2015-1/2023 were included. Goiter was defined as lobe ≥4 cm. For analysis purpose, goiters measuring 4-8 cm and ≥8 cm were defined as large and extremely large goiters, respectively. For malignancy definition, tumor<1 cm in their largest diameter were excluded from study. Collected data included demographics, cytology, histology and postoperative complication. RESULTS:144 goiters from 111 patients were included. The most common indication for surgery was symptoms (55 %). Compared with large goiter, extremely large goiters demonstrated a trend for tracheal narrowing on pre-operative CT findings (23 % vs. 45 %, p = 0.07 respectively). Overall differentiated thyroid carcinoma (DTC) rate was 17 % (25/144) without statistical difference between groups (p = 0.89). Within goiters with pre-operative benign cytology, the DTC rate was 17 % (7/43). Follicular variant of papillary thyroid cancer was the most common type for both groups. Nodular hyperplasia was significantly associated with extremely large goiters (53 % vs. 73 %, p = 0.03). No significant difference was found in transient hypocalcemia (48 % [15/31] vs. 41 % [5/12], p = 0.6) and other complications' rate between extremely large goiters and the control group. CONCLUSION:When discussing management options for patients with goiters, the size of the goiter should not regarded as a higher risk for complications or malignancy, yet the relatively high malignancy rate found should be taken under consideration for resection.

Context The severity of visceral adipose tissue (VAT) inflammation in individuals with obesity is thought to signify obesity subphenotype(s) associated with higher cardiometabolic risk. Yet, this tissue is not accessible for direct sampling in the nonsurgical patient.Objective We hypothesized that circulating miRNAs (circ-miRs) could serve as biomarkers to distinguish human obesity subgroups with high or low extent of VAT inflammation.Methods Discovery and validation cohorts of patients living with obesity undergoing bariatric surgery (n = 35 and 51, respectively) were included. VAT inflammation was classified into low/high based on an expression score derived from the messenger RNA levels of TNFA, IL6, and CCL2 (determined by reverse transcription polymerase chain reaction). Differentially expressed circ-miRs were identified, and their discriminative power to detect low/high VAT inflammation was assessed by receiver operating characteristic-area under the curve (ROC-AUC) analysis.Results Fifty three out of 263 circ-miRs (20%) were associated with high-VAT inflammation according to Mann-Whitney analysis in the discovery cohort. Of those, 12 (12/53 = 23%) were differentially expressed according to Deseq2, and 6 significantly discriminated between high- and low-VAT inflammation with ROC-AUC greater than 0.8. Of the resulting 5 circ-miRs that were differentially abundant in all 3 statistical approaches, 3 were unaffected by hemolysis and validated in an independent cohort. Circ-miRs 181b-5p, 1306-3p, and 3138 combined with homeostatic model assessment of insulin resistance (HOMA-IR) exhibited ROC-AUC of 0.951 (95% CI, 0.865-1) and 0.808 (95% CI, 0.654-0.963) in the discovery and validation cohorts, respectively, providing strong discriminative power between participants with low- vs high-VAT inflammation. Predicted target genes of these miRNAs are enriched in pathways of insulin and inflammatory signaling, circadian entrainment, and cellular senescence.Conclusion Circ-miRs that identify patients with low- vs high-VAT inflammation constitute a putative tool to improve personalized care of patients with obesity.

Purpose: To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods: Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) > 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (>38 degrees C) within 48 hours of drug administration. Results: Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 degrees C P < .001) but remained below 38 degrees C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P = .009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P = .8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P = .004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion: In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab.