The Urinary Proteomic Profile Implicates Key Regulators for Urologic Chronic Pelvic Pain Syndrome (UCPPS): A MAPP Research Network Study

Urologic chronic pelvic pain syndrome (UCPPS) is a condition of unknown etiology characterized by pelvic pain and urinary frequency and/or urgency. As the proximal fluid of this syndrome, urine is an ideal candidate sample matrix for an unbiased study of UCPPS. In this study, a large, discovery-phase, TMT-based quantitative urinary proteomics analysis of 244 participants was performed. The participants included patients with UCPPS (n = 82), healthy controls (HC) (n = 94), and disparate chronic pain diseases, termed positive controls (PC) (n = 68). Using training and testing cohorts, we identified and validated a small and distinct set of proteins that distinguished UCPPS from HC (n = 9) and UCPPS from PC (n = 3). The validated UCPPS: HC proteins were predominantly extracellular matrix/extracellular matrix modifying or immunomodulatory/host defense in nature. Significantly varying proteins in the UCPPS: HC comparison were overrepresented by the members of several dysregulated biological processes including decreased immune cell migration, decreased development of epithelial tissue, and increased bleeding. Comparison with the PC cohort enabled the evaluation of UCPPS-specific upstream regulators, contrasting UCPPS with other conditions that cause chronic pain. Specific to UCPPS were alterations in the predicted signaling of several upstream regulators, including alpha-catenin, interleukin-6, epidermal growth factor, and transforming growth factor beta 1, among others. These findings advance our knowledge of the etiology of UCPPS and inform potential future clinical translation into a diagnostic panel for UCPPS.     

Associations of ApoE4 status and DHA supplementation on plasma and CSF lipid profiles and entorhinal cortex thickness

Apolipoprotein ε allele 4 (APOE4) influences the metabolism of polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA). The entorhinal cortex (EC) in the brain is affected early in Alzheimer's disease and is rich in DHA. The purpose of this study is to identify the effect of APOE4 and DHA lipid species on the EC. Plasma and cerebrospinal fluid (CSF) lipidomic measurements were obtained from the DHA Brain Delivery Pilot, a randomized clinical trial of DHA supplementation (n = 10) versus placebo (n = 12) for six months in nondemented older adults stratified by APOE4 status. Wild-type C57B6/J mice were fed a high or low DHA diet for 6 months followed by plasma and brain lipidomic analysis. Levels of phosphatidylcholine DHA (PC 38:6) and cholesterol ester DHA (CE 22:6) had the largest increases in CSF following supplementation (P < 0.001). DHA within triglyceride (TG) lipids in CSF strongly correlated with corresponding plasma TG lipids, and differed by APOE4, with carriers having a lower increase than noncarriers. Changes in plasma PC DHA had the strongest association with changes in EC thickness in millimeters, independent of APOE4 status (P = 0.007). In mice, a high DHA diet increased PUFAs within brain lipids. Our findings demonstrate an exchange of DHA at the CSF-blood barrier and into the brain within all lipid species with APOE having the strongest effect on DHA-containing TGs. The correlation of PC DHA with EC suggests a functional consequence of DHA accretion in high density lipoprotein for the brain.     

Withdrawal of Denosumab in Patients With Primary Hyperparathyroidism: A Follow-up Report of the DENOCINA Study

ObjectivesWe investigated the development in the primary outcomes: changes in bone mineral density (BMD) measured by dual x-ray absorptiometry at the lumbar spine, total hip, and femoral neck after 2 years.MethodsIn patients with primary hyperparathyroidism, we investigated the effects of 30-mg cinacalcet per day plus 60 denosumab every 6 months for 1 year (Deno group), versus denosumab plus placebo for 1 year (DenoPlacebo-group), versus placebo plus placebo injection for 1 year (Placebo group). After the study’s termination, most patients receiving denosumab were switched to bisphosphonate treatment.ResultsForty-three out of 45 participants were subject to follow-up. A total of 35 patients completed a 2-year follow-up dual x-ray absorptiometry-scan (Deno: n = 13; DenoPlacebo: n = 12; and Placebo: n = 10). None of the groups showed statistically significant changes in BMD or experienced decreases in mean BMD below the study’s baseline level. Overall, the changes in T-scores from the final study measurement to follow-up were similar among the groups (P = .38 for lumbar spine T-score, .63 for total hip, and .97 for femoral neck by 1-way ANOVA). P-calcium was not different over time (P = .20 for change over time and P = .08 for the difference between the groups by repeated measures ANOVA). A total of 5 participants suffered a fracture during the study or follow-up periods, all but one was in the placebo group.ConclusionEvidence suggests that it is possible to at least maintain BMD, and thus potentially lower the fracture risk by a short course of denosumab followed by antiresorptive therapy, where applicable in patients with primary hyperparathyroidism.     

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.     

Associations of Urinary Polycyclic Aromatic Hydrocarbons With Bone Mineral Density at Specific Body Sites in U.S. Adults,National Health and Nutrition Examination Survey 2001 to 2004

ObjectiveWe aimed to analyze the association between certain types of urinary polycyclic aromatic hydrocarbons (PAHs) and bone mineral density (BMD) at specific sites of the body.MethodsA total of 2978 eligible participants from the National Health and Nutrition Examination Survey 2001 to 2004 were included in this study. Data of 8 urinary PAHs and BMDs of 3 skeleton sites and the total body were analyzed. Univariate and multivariate linear regression analyses were performed to explore the association between urinary PAHs and BMDs. Subgroup analyses stratified by sex and body mass index were also performed.ResultsAfter adjustment for all confounders, elevated 3-fluorene (β = 0.046; 95% confidence intervals [CIs], 0.007-0.084) and 2-fluorene (β = 0.054; 95% CI, 0.007-0.100) levels were associated with greater left arm BMD, whereas no statistical differences were observed in the relationship between other PAHs and BMDs (all P > .05). Higher 3-fluorene and 2-fluorene levels were still associated with increased left arm BMD in men (P < .05), whereas the higher 2-phenanthrene level was related to decreased left arm BMD (β = ?0.062; 95% CI, ?0.105 to ?0.019), right arm BMD (β = ?0.059; 95% CI, ?0.091 to ?0.027), and total BMD (β = ?0.065; 95% CI, ?0.119 to ?0.012) in women. Similar results were also found in different body mass index populations (all P < .05).ConclusionCertain urinary PAHs are associated with BMDs at specific body sites. Future studies are needed to illustrate the mechanisms behind the association to establish a causal relationship.     

Prevalence,Subtype Classification,and Outcomes of Treatment of Primary Aldosteronism: A Prospective Study in China

ObjectiveTo investigate the prevalence of primary aldosteronism (PA) among participants with hypertension, evaluate the concordance of PA classification between adrenal computed tomography and adrenal venous sampling, and compare the outcomes of surgery and medication for unilateral PA.MethodsA prospective study was conducted among all inpatients with hypertension (n = 7594) at the National Center for Cardiovascular Diseases, China, from May 2016 to April 2018.ResultsOf the 7594 participants, 8.12% (n = 617) with plasma aldosterone-renin ratio ≥3.7 were possible PA cases. Three hundred sixty-seven cases with plasma aldosterone-renin ratio ≥3.7 and plasma aldosterone concentration ≥10 ng/dL were confirmed using the recumbent saline infusion test (69.20%, 182 of 263) or the captopril challenge test (66.5%, 69 of 104, P > .05). The prevalence of PA was 3.31% (n = 251). Of the 251 patients with PA, all of them had multiple comorbidities, and 49.40% (n = 124) had spontaneous hypokalemia. The concordance of PA classification between adrenal computed tomography and adrenal venous sampling was only 47.11%. The patients’ blood pressure declined to normal ranges in the adrenalectomy (85.71%, 30 of 35) and spironolactone (63.04%; 29 of 46) groups (P < .05). Furthermore, hypokalemia was normalized in the adrenalectomy (100.00%; 26 of 26) and spironolactone (94.74%; 18 of 19) groups.ConclusionIt is necessary to incorporate PA screening into routine practice for those with hypertension in the Chinese population. This will assist in ensuring that the best therapeutic schedule based on PA subtypes is devised. Additionally, as a result, it may contribute to restoring the blood pressure levels and reducing the prevalence of comorbidities in these patients with PA.     

Proteomic Discovery of Plasma Protein Biomarkers and Development of Models Predicting Prognosis of High-Grade Serous Ovarian Carcinoma

Ovarian cancer is one of the most lethal female cancers. For accurate prognosis prediction, this study aimed to investigate novel, blood-based prognostic biomarkers for high-grade serous ovarian carcinoma (HGSOC) using mass spectrometry–based proteomics methods. We conducted label-free liquid chromatography–tandem mass spectrometry using frozen plasma samples obtained from patients with newly diagnosed HGSOC (n = 20). Based on progression-free survival (PFS), the samples were divided into two groups: good (PFS ≥18 months) and poor prognosis groups (PFS <18 months). Proteomic profiles were compared between the two groups. Referring to proteomics data that we previously obtained using frozen cancer tissues from chemotherapy-naïve patients with HGSOC, overlapping protein biomarkers were selected as candidate biomarkers. Biomarkers were validated using an independent set of HGSOC plasma samples (n = 202) via enzyme-linked immunosorbent assay (ELISA). To construct models predicting the 18-month PFS rate, we performed stepwise selection based on the area under the receiver operating characteristic curve (AUC) with 5-fold cross-validation. Analysis of differentially expressed proteins in plasma samples revealed that 35 and 61 proteins were upregulated in the good and poor prognosis groups, respectively. Through hierarchical clustering and bioinformatic analyses, GSN, VCAN, SND1, SIGLEC14, CD163, and PRMT1 were selected as candidate biomarkers and were subjected to ELISA. In multivariate analysis, plasma GSN was identified as an independent poor prognostic biomarker for PFS (adjusted hazard ratio, 1.556; 95% confidence interval, 1.073–2.256; p = 0.020). By combining clinical factors and ELISA results, we constructed several models to predict the 18-month PFS rate. A model consisting of four predictors (FIGO stage, residual tumor after surgery, and plasma levels of GSN and VCAN) showed the best predictive performance (mean validated AUC, 0.779). The newly developed model was converted to a nomogram for clinical use. Our study results provided insights into protein biomarkers, which might offer clues for developing therapeutic targets.     

An investigation of the flexion relaxation ratio in adults with and without a history of self-reported low back pain and transient sitting-induced pain

It is unknown whether the presence of sitting-induced pain or a clinical history of low back pain (LBP) changes spine function outcomes such as the flexion relaxation ratio (FRR). The purpose of this investigation was to determine whether sitting-induced pain or a history of non-specific LBP results in a different FRR. Forty-seven participants were instrumented with surface electromyography over erector spinae at L1, and accelerometers at L1 and S2. Standing maximum lumbar flexion trials were taken preceding and following a 1-hour sitting trial. Pain ratings during sitting and history of LBP were used to group participants for analysis. FRR values taken after the sitting exposures were compared between those that did and did not develop pain during sitting. Baseline FRR values were compared participants with and without a history of LBP. No significant differences in FRR were found for either pain groups (p = 0.11) or clinical history (p = 0.85). Lack of differences may be due to participants not currently experiencing a clinical episode of pain when the ratio was measured and/or because 1-hour sitting exposure was not long enough to induce pain modulation. The findings suggest that neither sitting-induced pain development or clinical history need to be controlled to prevent confounding of FRR.     

Unique features of epicardial ventricular arrhythmias/premature ventricular complexes ablated from coronary venous system in veteran population

IntroductionVentricular arrhythmias/premature ventricular complexes (VA/PVCs) that can be ablated from within the coronary venous system (CVS) have not been described in the United States Veterans Health Administration (VHA) population. We retrospectively studied the VA/PVCs ablations that were performed in the VHA population.MethodsData from 42 consecutive patients who underwent VA/PVCs ablation at Veterans Affairs Hospital, Indianapolis, IN, with 44 VA/PVCs was included in the study. Patients were divided into two groups (CVS group [n = 10], and non-CVS group [n = 32]) based on where the earliest pre-systolic activation was seen with >95% pacematch.ResultsThe mean age in CVS group was 65 ± 8 years versus 64 ± 12 years (p = 0.69) in non-CVS group. Overall there was a statistically significant reduction in PVC burden post ablation (27.7% (pre-ablation) versus 4.7% (post-ablation). In the 10 patients in the CVS group, either ablation or catheter-related mechanical trauma resulted in complete (n = 6 [60%]) or partial (n = 4 [40%]) long-term suppression of VA/PVCs. Right bundle branch block-type VA/PVC (9/11: 82%) was the most common morphology in the CVS group, whereas in the non-CVS group, this type was seen in only 3/33 (9%). The CVS group (25% of total VA/PVCs) had shorter activation time compared to non CVS group.ConclusionIn our experience VA/PVCs with electrocardiograms suggestive of epicardial origin can often be safely and successfully ablated within the coronary venous system. These arrhythmias have unique features in Veterans patient population.     

Resistin,Elastase, and Lactoferrin as Potential Plasma Biomarkers of Pediatric Inflammatory Bowel Disease Based on Comprehensive Proteomic Screens

Inflammatory bowel disease (IBD) is an immune-mediated chronic inflammation of the intestine, which can present in the form of ulcerative colitis (UC) or as Crohn’s disease (CD). Biomarkers are needed for reliable diagnosis and disease monitoring in IBD, especially in pediatric patients. Plasma samples from a pediatric IBD cohort were interrogated using an aptamer-based screen of 1322 proteins. The elevated biomarkers identified using the aptamer screen were further validated by ELISA using an independent cohort of 76 pediatric plasma samples, drawn from 30 CD, 30 UC, and 16 healthy controls. Of the 1322 proteins screened in plasma from IBD patients, 129 proteins were significantly elevated when compared with healthy controls. Of these 15 proteins had a fold change greater than 2 and 28 proteins had a fold change >1.5. Neutrophil and extracellular vesicle signatures were detected among the elevated plasma biomarkers. When seven of these proteins were validated by ELISA, resistin was the only protein that was significantly higher in both UC and CD (p < 0.01), with receiver operating characteristic area under the curve value of 0.82 and 0.77, respectively, and the only protein that exhibited high sensitivity and specificity for both CD and UC. The next most discriminatory plasma proteins were elastase and lactoferrin, particularly for UC, with receiver operating characteristic area under the curve values of 0.74 and 0.69, respectively. We have identified circulating resistin, elastase, and lactoferrin as potential plasma biomarkers of IBD in pediatric patients using two independent diagnostic platforms and two independent patient cohorts.     

Lycopene is superior to moringa in improving fertility markers in diet-induced obesity male rats

Obesity is a condition of chronic tissue inflammation and oxidative stress that poses as a risk factor for male infertility. Moringa oleifera oil extract is known to have cholesterol-lowering properties and a potential to treat obesity, while lycopene is a potent antioxidant. We hypothesize that Moringa or lycopene may improve male fertility markers in an animal model of diet-induced obesity. Male Albino rats (n = 60) were randomized to receive regular chow (RC) or high-fat diet (HFD) for 12 weeks (n = 30 each). Animals in each arm were further randomized to receive gavage treatment with corn oil (vehicle), lycopene (10 mg/kg), or Moringa (400 mg/kg) for four weeks starting on week 9 (n = 10 each). Animals were sacrificed at 12 weeks, and blood was collected to assess lipid profile, serum testosterone, and gonadotropin levels. The testes and epididymides were removed for sperm analysis, oxidative stress and inflammatory markers, and histopathological assessment. In comparison to their RC littermates, animals on HFD showed an increase in body weights, serum lipids, testosterone and gonadotrophin levels, testicular oxidative stress and inflammatory markers, as well as sperm abnormalities and disrupted testicular histology. Moringa or lycopene reduced body weight, improved oxidative stress, and male fertility markers in HFD-fed animals with lycopene exhibiting better anti-antioxidant and anti-lipidemic effects. Lycopene is superior to Moringa in improving male fertility parameters, possibly by attenuating oxidative stress.     

Patient Understanding of Discharge Instructions for Home Diabetes Self-Management and Risk for Hospital Readmission and Emergency Department Visits

ObjectiveThe primary objective of this study was to examine the patient comprehension of diabetes self-management instructions provided at hospital discharge as an associated risk of readmission.MethodsNoncritically ill patients with diabetes completed patient comprehension questionnaires (PCQ) within 48 hours of discharge. PCQ scores were compared among patients with and without readmission or emergency department (ED) visits at 30 and 90 days. Glycemic measures 48 hours preceding discharge were investigated. Diabetes Early Readmission Risk Indicators (DERRIs) were calculated for each patient.ResultsOf 128 patients who completed the PCQ, scores were similar among those with 30-day (n = 31) and 90-day (n = 54) readmission compared with no readmission (n = 72) (79.9 ± 14.4 vs 80.4 ± 15.6 vs 82.3 ± 16.4, respectively) or ED visits. Clarification of discharge information was provided for 47 patients. PCQ scores of 100% were achieved in 14% of those with and 86% without readmission at 30 days (P = .108). Of predischarge glycemic measures, glycemic variability was negatively associated with PCQ scores (P = .035). DERRIs were significantly higher among patients readmitted at 90 days but not 30 days.ConclusionThese results demonstrate similar PCQ scores between patients with and those without readmission or ED visits despite the need for corrective information in many patients. Measures of glycemic variability were associated with PCQ scores but not readmission risk. This study validates DERRI as a predictor for readmission at 90 days.     

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort

ObjectiveTo determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation.MethodsWe used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively.ResultsThe sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates.ConclusionThere is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.     

Differences between sexes in thermoregulatory responses and exercise time during endurance exercise in a hot environment following pre-cooling with ice slurry ingestion

This study aimed to examine differences between sexes in thermoregulatory responses and exercise time after ice slurry ingestion in a hot environment. Twenty-four healthy adults (male n = 12, body weight (BW) = 65.8 ± 10.3; female n = 12, BW = 58.2 ± 10.0) ingested 7.5 g/kg of either ice slurry at −1 °C (ICE) or control water at 20 °C (CON) before cycling at 55%VO₂ max in a hot environment (controlled at 38 °C, 40% relative humidity). Rectal (Tre) and skin (Tsk) temperature, heart rate, sweat rate, respiratory gases, ratings of thermal sensation (TS), thermal comfort (TC), and rating of perceived exertion (RPE) were measured. Ice slurry did not improve exercise time in both sexes despite Tre was significantly lower in ICE than CON in both sexes. Tre, Tsk, HR, sweat rate and TS did not differ between sexes. TC and RPE in ICE were significantly higher during exercise in males than in females. In conclusion, there were no sex differences in the effects of pre-cooling with ice slurry ingestion; however, pre-cooling with ice slurry may be more effective in mitigating ratings of TC and RPE in females than males.     

Etiology-, Sex-, and Tumor Size-Based Differences in Adrenocorticotropin-Dependent Cushing Syndrome

ObjectiveTo examine demographic, clinical, and biochemical differences in patients with adrenocorticotropin (ACTH)-dependent Cushing syndrome (CS) based on etiology, sex, and tumor size.MethodsThis was a single-center study of 211 patients with ACTH-dependent CS followed for 35 years. Patients were stratified into 3 groups based on etiology: Cushing disease (CD)/transsphenoidal surgery, Cushing disease/total bilateral adrenalectomy (CD/TBA), and ectopic ACTH secretion (EAS). Patients were also stratified based on sex and tumor size (nonvisualized, microadenoma, and macroadenoma).ResultsCD was the commonest cause of ACTH-dependent CS (190; 90%). Most patients presented in the third decade (median age, 29 years). Clinical features, cortisol, and ACTH were significantly greater in the EAS group. The CD/TBA group had more nonvisualized tumors (22% vs 8%; P = .000) and smaller tumor size (4 vs 6 mm; P = .001) compared with the CD/transsphenoidal surgery group. There was female predominance in CD (2.06:1) and male predominance in EAS (2:1). Men had shorter duration of symptoms (2 years; P = .014), were younger (23 years; P = .001), had lower body mass index (25.1 kg/m²; P = .000), and had more severe disease (low bone mineral density, hypokalemia). Macroadenomas were frequent (46; 24.2%), and ACTH correlated with tumor size in CD (r = 0.226; P = .005).ConclusionOur cohort presented at an earlier age than the Western population with a distinct, but slightly lower, female predilection. Patients with CD undergoing TBA had frequent negative imaging. Men had a clinical profile suggesting aggressive disease. Microadenoma and macroadenoma were difficult to distinguish on a clinicobiochemical basis.     

Bone Mineral Density of the 1/3 Radius Refines Osteoporosis Diagnosis,Correlates With Prevalent Fractures,and Enhances Fracture Risk Estimates

ObjectiveTo investigate the added value of 1/3 radius (1/3R) for the diagnosis of osteoporosis by spine and hip sites and its correlation with prevalent fractures and predicted fracture risk.MethodsFracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fractures (MOF) with/without trabecular bone score were considered proxy for fracture risk. The contribution of 1/3R to risk prediction was depicted via linear regression models with FRAX score as the dependent variable—first only with central and then with radius T-score as an additional covariate. Significance of change in the explained variance was compared by F-test.ResultsThe study included 1453 patients, 86% women, aged 66 ± 10 years. A total of 32% (n = 471) were osteoporotic by spine/hip and 8% (n = 115) by radius only, constituting a 24.4% increase in the number of subjects defined as osteoporotic (n = 586, 40%). Prior fracture prevalence was similar among patients with osteoporosis by spine/hip (17.4%) and radius only (19.1%) (P = .77).FRAX prediction by a regression model using spine/hip T-score yielded explained variance of 51.8% and 49.9% for MOF and 39.8% and 36.4% for hip (with/without trabecular bone score adjustment, respectively). The contribution of 1/3R was statistically significant (P < .001) and slightly increased the explained variance to 52.3% and 50.4% for MOF and 40.9% and 37.4% for hip, respectively.ConclusionReclassification of BMD results according to radius measurements results in higher diagnostic output. Prior fractures were equally prevalent among patients with radius-only and classic-site osteoporosis. FRAX tool performance slightly improved by incorporating radius BMD. Whether this approach may lead to a better fracture prediction warrants further prospective evaluation.     

Pirfenidone attenuates the profibrotic contractile phenotype of differentiated human dermal myofibroblasts

Dysregulated wound healing after burn injury frequently results in debilitating hypertrophic scarring and contractures. Myofibroblasts, the main effector cells for dermal fibrosis, develop from normal fibroblasts via transforming growth factor beta 1 (TGF-β1). During wound healing, myofibroblasts produce extracellular matrix (ECM) proteins, modulate ECM stability, and contract the ECM using alpha smooth muscle actin (α-SMA) in contractile stress fibers. The antifibrotic pirfenidone has previously been shown to inhibit the initial differentiation of fibroblasts into myofibroblasts in vitro and act as a prophylactic measure against hypertrophic scar development in a mouse burn model. To test whether pirfenidone affects differentiated myofibroblasts, we investigated the in vitro effects of pirfenidone treatment after three to five days of stimulation with TGF-β1. In assays for morphology, protein and gene expression, and contractility, pirfenidone treatment produced significant effects. Profibrotic gene expression returned to near-normal levels, further α-SMA protein expression was prevented, and cell contraction within a stressed collagen matrix was reduced. These in vitro results promote pirfenidone as a promising antifibrotic agent to treat existing scars and healing wounds by mitigating the effects of differentiated myofibroblasts.     

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy

ObjectiveWomen with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment.MethodsWomen were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly.ResultsAfter delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery.ConclusionFor patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.     

The Added and Interpretative Value of CGM-Derived Parameters in Type 1 Diabetes Depends on the Level of Glycemic Control

ObjectiveIn type 1 diabetes mellitus (T1DM) management, continuous glucose monitoring (CGM)-derived parameters can provide additional insights, with time in range (TIR) and other parameters reflecting glycemic control and variability being put forward. This study aimed to examine the added and interpretative value of the CGM-derived indices TIR and coefficient of variation (CV%) in T1DM patients stratified according to their level of glycemic control by means of HbA1C.MethodsT1DM patients with a minimum disease duration of 10 years and without known macrovascular disease were enrolled. Patients were equipped with a blinded CGM device for 7 days. TIR and time spent in hypoglycemia and hyperglycemia were determined, and CV% was used as a parameter for glycemic variability. Pearson (r) and Spearman correlations (r_s) and a regression analysis were used to examine associations.ResultsNinety-five patients (age: 45 ± 10 years; HbA1C level: 7.7% ± 0.8% [61 ± 7 mmol/mol]) were included (mean blood glucose [MBG]: 159 ± 31 mg/dL; TIR: 55.8% ± 14.9%; CV%: 43.5% ± 7.8%) and labeled as having good (HbA1C level ≤7% [≤53 mmol/mol]; n = 20), moderate (7%-8%; n = 44), or poor (>8% [>64 mmol/mol]; n = 31) glycemic control. HbA1C was significantly associated with MBG (r_s = 0.48, P < .001) and time spent in hyperglycemia (total: r_s = 0.52; level 2: r = 0.46; P < .001) but not with time spent in hypoglycemia and CV%, even after an analysis of the HbA1C subgroups. Similarly, TIR was negatively associated with HbA1C (r = −0.53; P < .001), MBG (r_s = −0.81; P < .001), and time spent in hyperglycemia (total: r_s = −0.90; level 2: r_s = −0.84; P < .001) but not with time in hypoglycemia. The subgroup analyses, however, showed that TIR was associated with shorter time spent in level-2 hypoglycemia in patients with good (r_s = −0.60; P = .007) and moderate (r_s = −0.25; P = .047) glycemic control. In contrast, CV% was strongly positively associated with time in hypoglycemia (total: r_s = 0.78; level 2: r_s = 0.76; P < .001) but not with TIR or time in hyperglycemia in the entire cohort, although the subgroup analyses showed that TIR was negatively associated with CV% in patients with good glycemic control (r = −0.81, P < .001) and positively associated in patients with poor glycemic control (r = +0.47; P < .01).ConclusionThe CGM-derived metrics TIR and CV% are related to clinically important situations, TIR being strongly dependent on hyperglycemia and CV% being reflective of hypoglycemic risk. However, the interpretation and applicability of TIR and CV% and their relationship depends on the level of glycemic control of the individual patient, with CV% generally adding less clinically relevant information in those with poor control. This illustrates the need for further research and evaluation of composite measures of glycemic control in T1DM.     

The frequencies of Kidd blood group antigens and phenotypes among Saudi blood donors in Southwestern Saudi Arabia

BackgroundThe patients who require transfusion are prevalent in the Jazan Province, Saudi Arabia. Therefore, it is essential to know the frequency of blood group antigens in such a population. The Kidd blood group system (JK) has two antithetical antigens, Jk^a and Jk^b. Antibodies to these antigens may result in delayed hemolytic transfusion reactions. The present study investigated the frequencies of Jk^a and Jk^b and the phenotypes among Saudi blood donors living in the Jazan Province.MethodsOne hundred and forty-three samples from anonymous Saudi volunteer blood donors in the Jazan Province were serotype to detect Jk^a and Jk^b using gel card technology and determine the phenotypes of the JK blood group system.ResultsThe prevalence of Jk^a and Jk^b antigens were 90.64% (n = 126) and 69.40% (n = 93), respectively. The JK phenotypes were 34.96% Jk(a + b ? ) (n = 51), 12.59% Jk(a ? b + ) (n = 18), 52.45% Jk(a + b + ) (n = 75), and 0% Jk(a ? b ? ). The frequencies of the JK phenotypes in the Jazan population were significantly different from those in the Asian population (P < 0.05).ConclusionsWe reported the frequencies of the Jk^a and Jk^b antigens and the distribution of the JK phenotypes in a group of Saudi blood donors in the Jazan Province, Saudi Arabia. The phenotype Jk(a + b + ) was the most common among the study population. Furthermore, this study emphasizes the significance of identifying the frequency of JK antigens and phenotypes in the provinces of Saudi Arabia.