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BACKGROUND Caused by premature activation of the hypothalamic-pituitary-gonadal axis, there is increasing incidence of central precocious puberty (CPP), especially in girls. Makorin ring finger protein 3 (MKRN3), a maternal imprinted gene with a highly conserved sequence, is the most common genetic etiology associated with CPP. Approximately 50 different mutations in MKRN3 have been found in CPP. CASE SUMMARY This case report involves identical twin sisters presenting with premature thelarche at the age of 6 years. The left hand bone age of both patients revealed advanced age (9 years). Pelvic B ultrasound indicated enlargement of the ovaries. Luteinizing hormone (LH) releasing hormone testing confirmed CPP. Whole-exome sequencing detected the c.841C>T mutation in MKRN3, leading to a single base substitution, in the twins. This mutation was inherited from the father and paternal grandmother. After 3 mo of treatment with a gonadotropin-releasing hormone analog, levels of LH, follicle-stimulating hormone, and estradiol in the proband’s sister returned to normal levels. CONCLUSION Here, we report a rare mutation (c.841C>T) in MKRN3 in identical twin sisters with CPP.

Background: Cardiovascular disease (CVD) is the leading cause of death in haemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and is strongly associated with CVD events and mortality in HD patients. VC coexists with osteoporosis in many studies. Fibroblast growth factor 21 (FGF21) as an adipocytokines is a new hypoglycemic strategy and is inversely related to bone mineral density.Methods: To evaluate the contribution of FGF21 to VC in HD patients, we preliminary sreened 802 HD patients of two large HD centers in China. At last 388 HD patients were entered this cross-sectional study. We detected circulating FGF21 levels and measured the whole thoracic aorta calcification scores (TACS) and calcification scores of the three segments of thoracic aorta (TA), including ascending thoracic aorta (ATACS), aortic arch (AoACS), and descending thoracic aorta (DTACS) of our 388 HD patients. In addition, we pre-incubated human aortic endothelial cells (HAECs) with FGF21 in the presence or absence of parathyroid hormone (PTH) in vitro.Results: The median serum FGF21 level in HD patients was 11-fold higher than that in healthy controls. Ln(FGF21) was positively correlated with Ln(TACS+1), Ln(ATACS+1), Ln(AoACS+1) and Ln(DTACS+1) respectively in HD patients. Serum FGF21 was independently associated with TACS and ATACS, AoACS, and DTACS. FGF21 combined with age, calcium and intact parathyroid hormone demonstrated a high area under the curve (AUC=0.84) with optimal sensitivity (84%) and specificity (71%) for the prediction of VC in HD patients. Our vitro results showed that FGF21 enhanced the calcification effect of PTH on HAECs by increasing calcium deposition and endothelial-to-mesenchymal transition (EndMT).Conclusions: Circulating FGF21 was notably higher and was a potential predictor and promoter of VC in HD patients.Trial registration Chinese Clinical Trial Registry, identifier: ChiCTR1900028249. Registered 16 December 2019-Retrospectively registered,http://www.medresman.org.cn/uc/project/projectedit.aspx?proj=5981

Background The goal was to characterize retinal vasculature by quantitative analysis of arteriole-to-venule (A/V) ratio and vessel density in fundus photos taken with the PanOptic iExaminer System. Methods The PanOptic ophthalmoscope equipped with a smartphone was used to acquire fundus photos centered on the optic nerve head. Two fundus photos of a total of 19 eyes from 10 subjects were imaged. Retinal vessels were analyzed to obtain the A/V ratio. In addition, the vessel tree was extracted using deep learning U-NET, and vessel density was processed by the percentage of pixels within vessels over the entire image. Results All images were successfully processed for the A/V ratio and vessel density. There was no significant difference of averaged A/V ratio between the first (0.77 ± 0.09) and second (0.77 ± 0.10) measurements (P = 0.53). There was no significant difference of averaged vessel density (%) between the first (6.11 ± 1.39) and second (6.12 ± 1.40) measurements (P = 0.85). Conclusions Quantitative analysis of the retinal vasculature was feasible in fundus photos taken using the PanOptic ophthalmoscope. The device appears to provide sufficient image quality for analyzing A/V ratio and vessel density with the benefit of portability, easy data transferring, and low cost of the device, which could be used for pre-clinical screening of systemic, cerebral and ocular diseases.

The discovery of hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (PHI) has revolutionized the treatment strategy for renal anemia. However, the presence of multiple transcription targets of HIF raises safety concerns regarding HIF-PHI. Here, we explored the dose-dependent effect of MK-8617 (MK), a kind of HIF-PHI, on renal fibrosis. MK was administered by oral gavage to mice for 12 wk at doses of 1.5, 5, and 12.5 mg/kg. In vitro, the human proximal tubule epithelial cell line HK-2 was treated with increasing doses of MK administration. Transcriptome profiling was performed, and fibrogenesis was evaluated. The dose-dependent biphasic effects of MK on tubulointerstitial fibrosis (TIF) were observed in chronic kidney disease mice. Accordingly, high-dose MK treatment could significantly enhance TIF. Using RNA-sequencing, combined with in vivo and in vitro experiments, we found that Krüppel-like factor 5 (KLF5) expression level was significantly increased in the proximal tubular cells, which could be transcriptionally regulated by HIF-1α with high-dose MK treatment but not low-dose MK. Furthermore, our study clarified that HIF-1α–KLF5–TGF-β1 signaling activation is the potential mechanism of high-dose MK-induced TIF, as knockdown of KLF5 reduced TIF in vivo. Collectively, our study demonstrates that high-dose MK treatment initiates TIF by activating HIF-1α–KLF5–TGF-β1 signaling. These findings provide novel insights into TIF induction by high-dose MK (HIF-PHI), suggesting that the safety dosage window needs to be emphasized in future clinical applications.—Li, Z.-L., Lv, L.-L., Wang, B., Tang, T.-T., Feng, Y., Cao, J.-Y., Jiang, L.-Q., Sun, Y.-B., Liu, H., Zhang, X.-L., Ma, K.-L., Tang, R.-N., Liu, B.-C. The profibrotic effects of MK-8617 on tubulointerstitial fibrosis mediated by the KLF5 regulating pathway.

Introduction Osteoporosis is one of the important bone abnormalities in chronic kidney disease-mineral and bone disorder (CKD-MBD) and still lacks a sensitive biomarker to diagnose. Fibroblast growth factor 21 (FGF21) can stimulate bone loss in patients with diabetes and increase in CKD patients. In this study, we investigated whether FGF21 could serve as a biomarker to predict osteoporosis in a haemodialysis cohort. Methods We recorded demographic information, biochemical data, and serum FGF21 and FGF23 levels and measured the CT attenuation values of 339 haemodialysis patients from two large medical centres. We assessed the correlation of CT attenuation values with serum FGF21 and FGF23 levels and tested whether they were independent factors for osteoporosis. ROC curves were constructed to compare the prognostic value of FGF21 and FGF23 for osteoporosis. Results Based on the CT attenuation value, serum FGF21 levels were higher in our osteoporosis group (median 640.86 pg/ml vs. 245.46 pg/ml, P ˂ 0.01). Meanwhile, FGF21 (r = -0.136, P r = -0.151, P β = -0.067, P Conclusions FGF21 has a positive relationship with the incidence of osteoporosis in patients on haemodialysis. FGF21 combined with age is a good predictive biomarker for osteoporosis in patients on haemodialysis, especially those with less residual renal function.

Background and Aims The global diabetes mellitus (DM) prevalence in 2019 is estimated to be 9.3%. Approximately 20% to 40% of patients with DM develop diabetic nephropathy (DN). DN is the leading cause of end stage renal disease (ESRD). Inflammation is considered to be an important mechanism in the development of DM and persists for a long time before the occurrence of DN. Many studies demonstrated that decrease of endothelium glycocalyx (EG) was negatively correlated with proteinuria. Whether EG damage induced by inflammasome in DM patients leads to the occurrence of micro albuminuria (MA) and accelerating the progress of DKD is rarely studied. Method: This prospective, observational cohort study screened 300 diagnosed diabetic patients from departments of nephrology and endocrinology of our hospital. The exclusion criteria were: type 1 diabetes; acute infections; usage antibiotics within 3 months; kidney disease before; heart failure; malignancy. Finally 70 patients were invited to this study and were divided into type 2 DM (T2DM) group and type 2 diabetic nephropathy (T2DN) group. T2DM group were defined as patients with normal MA and without diabetic retinopathy (n=35). T2DN group were defined as patients with increased MA and diabetic retinopathy (n=35). Laboratory data were measured via routine laboratory methods. Heparan sulfate (HS) and interleukin 1 beta (IL-1β) were noted as EG biomarker and inflammasome biomarker respectively. Serum samples of patients were collected, and serum IL-1β and HS were measured by ELISA. SPSS 18.0 was used for all statistical analyses. Results: T2DN patients had higher serum IL-1β (27.85 vs. 21.35 pg/ml), higher HS (2.17 vs. 1.47 ng/ml), higher urea nitrogen (6.30 vs. 5.33 umol/L), higher CRP (2.03 vs. 0.81 mg/L), higher hemoglobin (128 vs. 141 g/L), higher neutrophil (4.1 vs. 3.4 × 109/L) and higher neutrophilic granulocyte percentage (63% vs. 56%) compared with T2DM patients (all P Conclusion T2DN patients had higher serum IL-1β and HS than T2DM patients in our study. In T2DN patients IL-1β was an independent associated factor of HS. The results suggested that the inflammasome may damage the EG in diabetic patients, which induced the occurrence of MA and accelerating the progress of DN.

Background and Aims Cardiovascular disease (CVD) is the leading cause of death in hemodialysis (HD) patients. Vascular calcification (VC) is dramatically accelerated and strongly associated with CVD events and mortality in HD patients. This study aimed to achieve 4 objectives using a population-based retrospective cohort of HD patients: (1)quantify the correlation between FGF21 and VC; (2)determine whether FGF21 is a novel risk factor for VC; (3)examine the predictive effect of FGF21 on VC; (4)explore the underlying mechanism of FGF21 in promoting VC, especially focused on the EndMT process, in cultured human aortic endothelial cells (HAECs). Method 802 HD patients were screened, at last 388 HD patients were eligible in the study. Serum FGF21 levels were assessed by ELISA kits. Chest radiographies of HD patients taken by multislice computed tomography were used to measure TACS. HD patients were divided into two groups : low TACS group (< median of TACS) and high TACS group (≧median of TACS). Univariate analyses were performed to compare the differences between two groups. Categorical data were compared using the Chi-square test. Stepwise multivariate linear regression analyses were employed to evaluate variables independently associated with TACS. The ROC curves were performed to calculate the AUC and compare the prognostic value of every independently associated factor or united factor to VC. Additionally HAECs was pretreated with FGF21 in the presence or absence of PTH. The formation of calcium deposits was analysed by Alizarin Red staining (ARS). PCR for the measurement of mRNA of CD31, RUNX2 and FSP1 to evaluate endothelial-to-mesenchymal transition (EndMT) of HAECs. Results Prevalence of VC was 70.1% in this study. Serum FGF21 levels of HD patients were 11-fold higher than controls (median 217 vs. 20 pg/ml). HD patients in the high TACS group had older age, higher FGF21, higher FGF23, longer dialysis vintage, higher incidence of hypertension and higher incidence of CVD (all P Conclusion This study is the first to show that serum FGF21 levels were significantly and independently correlated with VC in HD patients. Furthermore, FGF21 combined with PTH, calcium and age can significantly predict VC in HD patients. Additionally FGF21 aggravated the effect of PTH on calcium deposition and EndMT in HAECs. Taken together, our in vivo and in vitro results indicated that FGF21 was a novel predictor and promoter of VC in HD patients.

Background: Maturity-onset diabetes of the young type 2 (MODY2) is caused by mutations in the glucokinase (GCK) gene and is rare in the Chinese population. We report three Chinese families with MODY2 and the sequencing of the GCK gene. Methods: Three unrelated Chinese families with MODY2 and their pedigrees were investigated. In Family 1, the proband was a 7-year-old girl with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Her mother and maternal grandfather had IFG. In Family 2, the proband was a boy who had diabetes mellitus at 11 years. His sister had IFG. His father and grandmother had diabetes mellitus at 22 and 25 years, respectively. In Family 3, the proband was a boy who had IFG and IGT at 12 years. His sister had diabetes mellitus at 8 years. His father and grandfather had IFG and/or IGT. The GCK gene was directly sequenced. Results: Diabetes mellitus or IFG/IGT was found among three consecutive generations in three families. One novel nonsense heterozygous mutation in exon 5 (c.556 C>T, p.Arg 186 stop) was detected in Family 1. Another novel frameshift mutation in exon 4 (c.367-374dupTTCGACTA, p.Ile 126 fs) was found in Family 2. A previously reported, a missense heterozygous mutation in exon 5 (c.571 C>T, p.Arg 191Trp) was detected in Family 3. Conclusions: The thorough investigation of three Chinese families with MODY2 revealed two novel mutations and one known mutation. GCK gene sequencing helps in MODY2, especially when there is uncertain IFG or IGT.

Unchecked inflammation can result in severe diseases with high mortality, such as macrophage activation syndrome (MAS). MAS and associated cytokine storms have been observed in COVID-19 patients exhibiting systemic hyper-inflammation. Interleukin-18 (IL-18), a proinflammatory cytokine belonging to the IL-1 family, is elevated in both MAS and COVID-19 patients, and its level is known to correlate with the severity of COVID-19 symptoms. IL-18 binds its specific receptor IL-1 Receptor 5 (IL-1R5, also known as IL-18 Receptor alpha chain), leading to the recruitment of the co-receptor, IL-1 Receptor 7 (IL-1R7, also known as IL-18 Receptor beta chain). This heterotrimeric complex then initiates downstream signaling, resulting in systemic and local inflammation. Here, we developed a novel humanized monoclonal anti-IL-1R7 antibody to specifically block the activity of IL-18 and its inflammatory signaling. We characterized the function of this antibody in human cell lines, in freshly obtained peripheral blood mononuclear cells (PBMCs), and in human whole blood cultures. We found that the anti-IL-1R7 antibody significantly suppressed IL-18-mediated NFκB activation, reduced IL-18-stimulated IFNγ and IL-6 production in human cell lines, and reduced IL-18-induced IFNγ, IL-6 and TNFα production in PBMCs. Moreover, the anti-IL-1R7 antibody significantly inhibited LPS- and Candida albicans-induced IFNγ production in PBMCs, as well as LPS-induced IFNγ production in whole blood cultures. Our data suggest that blocking IL-1R7 could represent a potential therapeutic strategy to specifically modulate IL-18 signaling, and may warrant further investigation into its clinical potential for treating IL-18-mediated diseases, including MAS and COVID-19.

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder in which the adrenal cortex fails to respond appropriately to stimulation by adrenocorticotropic hormone (ACTH) to produce cortisol. The disease is characterized in laboratory testing by glucocorticoid deficiency and markedly elevated ACTH levels. FGD may present in infancy or early childhood with symptoms related to low cortisol and high ACTH, such as hyperpigmentation, severe hypoglycemia, failure to thrive and recurrent infections. Mutations in the MC2R accessory protein (MRAP) cause FGD types 2, which accounts for approximately 15–20% of FGD cases. Here, we report a female neonate of Chinese Han origin, who presented with noted hyperpigmentation at birth. Laboratory investigations revealed hypocortisolaemia (cortisol

Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P

Importance To our knowledge, a set of well-defined diagnostic criteria is not yet developed for the diagnosis of Vogt-Koyanagi-Harada (VKH) disease. Objective To develop and evaluate a set of diagnostic criteria for VKH disease using data from Chinese patients. Design, Setting, and Participants This case-control study reviewed medical records of patients from a tertiary referral center between October 2011 and October 2016. Data from 634 patients with VKH disease and 623 patients with non-VKH uveitis from southern China were used to develop the Diagnostic Criteria for VKH Disease (DCV). Data from an additional group of 537 patients with a definite VKH disease diagnosis and 525 patients with non-VKH uveitis from northern China were used to evaluate the diagnostic criteria. Main Outcomes and Measures Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and receiver operating characteristic. Results Of the 1257 patients used to construct the DCV, 665 (52.9%) were male, and the mean (SD) age at disease onset was 38.6 (13.6) years. The 3-class model and 21 clinical findings were selected by latent class analysis. Variables with a high positive rate in the early-phase or late-phase VKH group or high specificity constituted essential parameters. Constellations of these essential parameters constructed the DCV. The sensitivity and NPV of the DCV were higher than those of the Revised Diagnostic Criteria for VKH Disease (RDC) (sensitivity: 94.6% vs 71.9%; difference, 22.7%; 95% CI, 18.5-27.0; NPV: 94.3% vs 76.6%; difference, 17.7%; 95% CI, 13.9-21.5). The specificity and PPV of the DCV were not different from that of the RDC (specificity: 92.2% vs 93.9%; difference, 1.7%; 95% CI, −1.4 to 4.8; PPV: 89.3% vs 92.3%; difference, 3.0%; 95% CI, −1.4 to 4.8). The area under the receiver operating characteristic curve of the DCV and the RDC were 0.934 (95% CI, 0.917-0.951) and 0.829 (95% CI, 0.803-0.855), respectively. Conclusions and Relevance The DCV were developed and evaluated using data from Chinese patients with VKH disease and showed a high sensitivity, NPV, and area under the receiver operating characteristic curve in comparison with the RDC. However, they were developed using a retrospective analysis and should be evaluated in prospective studies in other racial/ethnic populations.

Backgroud/aims: Leptin has recently been found to play an important role in the development of autoimmune diseases. Our study is designed to investigate the expression and possible role of leptin in the pathogenesis of Vogt–Koyanagi–Harada (VKH) disease, one of the common types of autoimmune uveitis in China. Methods: Leptin levels in serums of 20 active, 16 inactive VKH patients and 20 healthy controls were measured using ELISA. Peripheral blood mononuclear cells (PBMCs) separated from active VKH patients and healthy controls were cultured with recombinant human leptin, and cell proliferation was assayed by [3H]-TdR incorporation. Cytokine levels in the supernatant of PBMCs cultured in mixed lymphocyte reaction (MLR) upon stimulation with leptin were assayed by ELISA. Results: Our results showed that leptin was significantly increased in the serum of active VKH patients compared with that in inactive VKH patients and healthy controls. Leptin levels in active VKH patients remained markedly higher when divided by body mass index (BMI). PBMCs cultured with leptin induced a marked cell proliferation and profound secretion of IFN-γ and IL-17. Conclusion: These findings suggest that leptin may be involved in the development of VKH disease possibly by promoting an immune response.

Background CD8(+) regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The mechanisms of suppression by CD8(+) T cells in ACAID remain only poorly understood. TGF-beta 1 is considered as an inhibitory cytokine for immunosuppression in some models. The production of TGF-beta 1 by CD8(+) T cells in ACAID, and whether CD8+ T cells exert suppression through TGF-beta 1, is unknown. Methods The suppressive effect of CD8(+) T cells in ACAID mice was determined by a local adoptive transfer (LAT) assay. The production of TGF-beta 1 by CD8(+) T cells was measured by enzyme-linked immunosorbent assay (ELISA). Anti-TGF-beta 1 antibodies were used in the LAT assay to test if they could block the inhibitory effect of CD8(+) T cells. Results CD8(+) T cells from ACAID mice were shown to block the delayed-type hypersensitivity (DTH) response in an antigen-specific manner in a LAT assay. These CD8+ T cells secreted TGF-beta 1, and their suppression could partially be blocked by anti-TGF-beta 1 antibodies. Conclusions Our study confirms that CD8+ T cells from ACAID mice possess inhibitory properties. This population exerts part of its suppressive function via the production of TGF-beta 1.

BackgroundCD8+regulatory T cells (Treg) have been considered to be involved in a model of ocular-induced tolerance, known as anterior chamber-associated immune deviation (ACAID). The phenotype and characteristics of CD8+Treg in ACAID remain only poorly understood. Recent studies have reported that the CD94-Qa-1 system is implicated in the induction of ACAID CD8+Treg, but the functions and characteristics of CD8+CD94+T cells remain unclear.ResultsBoth mRNA and protein of CD94 and NKG2A were markedly up-regulated on splenic CD8+T cells of ACAID mice compared with controls. Flow cytometric analysis showed that very few CD8+CD94+T cells express granzyme B, perforin and Foxp3. CD8+CD94+T cells, but not CD8+CD94-T cells, magnetically isolated from the spleens of ACAID mice, produced large amounts of TGF-beta1 and exhibited suppressive activity in vitro. Neutralization of TGF-beta1 caused reversal of suppression mediated by CD8+CD94+T cells.ConclusionCD8+CD94+T cells from ACAID mice exhibited suppressive activity in association with enhanced expression of TGF-beta1, suggesting that CD8+Treg are mainly distributed in CD94+T cell subpopulations.

Abstract 5312 Patients with chronic kidney disease (CKD) have increased risks of endothelial dysfunction and thrombosis. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. von Willebrand factor (VWF), a well-known index of endothelial damage, has been reported to increase both in CKD and inflammatory states. ADAMTS13 is a specific VWF-cleaving protease, and some reports suggested that the ratio of VWF and ADAMTS13 maybe more useful in the diagnosis and treatment evaluation of patients in the prothrombotic state. So we assessed the relationships among endothelial dysfunction, ADAMTS13 activity, and levels of inflammatory cytokines in CKD patients. CKD patients were classified into 3 groups: chronic glomerulonephritis group (CGN, n = 31), idiopathic nephritic syndrome group (NS, n = 32), and lupus nephritis group (LN, n = 41). We measured the plasma levels of TNF-α, VWF antigen (VWF:Ag), and ADAMTS13 activity by using an ELISA-based method in CKD patients (n = 104) and normal controls (n = 32). The ratio of the VWF:Ag level to ADAMTS13 activity was calculated. The VWF:Ag level was significantly higher and the ADAMTS13 activity was significantly lower in all the disease groups than in the controls (P < 0.01). ADAMTS13 activity was lower in the NS group than in the CGN and LN groups (P < 0.05) (Table 1). The TNF-α (pg/mL) level was higher in the CKD group than in the control group (CGN: 3.19 ± 1.01; NS: 3.26 ± 1.18; LN: 3.24 ± 1.24; Control: 2.27 ± 1.23; P < 0.01; P < 0.01). TNF-α was positively correlated with the VWF:Ag level (r = 0.242, P = 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r = −0.193, P = 0.049). ADAMTS13 activity was negatively correlated with the cholesterol level in CKD patients (r = −0.2, P = 0.042). TNF-α level in CKD was positively correlated with the VWF:Ag level and negatively correlated with GFR, which suggests that inflammation might be a major cause of endothelial dysfunction and an index for renal function. The VWF:Ag level increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state. Table 1. The plasma VWF:Ag level, ADAMTS13 activity, and the VWF/ADAMTS13 ratio in the CGN, NS, LN, and control groups N VWF (%) ADAMTS13 (%) VWF/ADAMTS13 CGN 31 198.25 ± 140.20** 61.93 ± 22.47**# 3.83 ± 3.29** NS 32 149.94 ± 74.50** 48.87 ± 18.63** 3.42 ± 1.59** LN 41 234.75 ± 134.91**## 67.81 ± 22.30**## 3.79 ± 2.52** CONTROL 32 99.55 ± 21.37 94.37 ± 23.66 1.12 ± 0.37 vs. CONTROL ** P < 0.01; vs. NS ## p < 0.01, # P < 0.05 Disclosures: No relevant conflicts of interest to declare.