Prognostic Significance of Red Cell Distribution Width in Idiopathic Pulmonary Fibrosis and Combined Pulmonary Fibrosis Emphysema

ObjectiveThe red cell distribution width (RDW) is an inexpensive, readily available prognostic indicator of several diseases. RDW has been assessed as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) in only one study; furthermore, the relationship between the RDW and combined pulmonary fibrosis emphysema (CPFE) has yet to be reported.Subjects and MethodsThis single-center study was conducted between January 2015 and December 2018 in the Atatürk Chest Diseases and Chest Surgery Education and Research Hospital. Baseline characteristics, laboratory results, and survival status of patients were recorded.ResultsThe RDW value was significantly higher in the CPFE group than in the IPF group (median [IQR 25–75]; 16.8 [15.5–19] vs. 15.3 [13.7–16.8], p = 0.028). High RDW values were correlated with carbon monoxide diffusion capacity (DLCO) (r: −0.653 p = 0.001), 6-minute walking test (6MWT) distance (r: −0.361 p = 0.017), arterial partial oxygen pressure (PaO₂) (r: −0.692 p < 0.001), and systolic pulmonary arterial pressure (SPAP) (r: 0.349 p = 0.022) in patients with fibrotic lung disease. The RDW value was significantly higher in the exitus group than in the survivors (median [IQR 25–75]; 18.4 [15.4–19] vs. 15.2 [13.5–17.2], p = 0.016). A univariate Cox regression analysis identified DLCO, SPAP, PaO₂, and RDW as potential covariates of mortality. In a multivariate analysis, the DLCO (HR 1.21, 95% CI 1.11–1.47, p = 0.012) and RDW level (HR 1.65, 95% CI 1.09–2.47, p = 0.023) remained independent predictors of mortality.ConclusionHigh RDW values appear to be a simple prognostic factor in patients with IPF or CPFE.     

Myeloid dendritic cells in severe aplastic anemia patients exhibit stronger phagocytosis

BackgroundA deeper understanding of the pathogenesis of severe aplastic anemia (SAA) is urgently warranted to achieve better therapeutic effects. The objective of this study was to investigate the phagocytosis of myeloid dendritic cell (mDC) in SAA patients.MethodsMyeloid dendritic cells were induced in vitro from bone marrow mononuclear cells from 26 SAA patients and 12 normal controls (HCs). The phagocytosis of mDCs was detected by flow cytometry using FITC‐Dextran (40KD), and its correlation with the immune status and severity of the disease was analyzed.ResultsThe phagocytosis of mDC from untreated SAA patients was significantly stronger than that from complete remission group and HC group (p < 0.05). There was no statistical difference between the latter two groups (p > 0.05). The phagocytosis of mDC from SAA patients correlated positively with the concentration of interleukin (IL)‐2 (r = 0.389, p < 0.05), and IL‐4 (r = 0.556, p < 0.05), negatively with CD4⁺/CD8⁺ ratio (r = −0.421, p < 0.05). It also had negative correlations with the level of hemoglobin (r = −0.393, p < 0.05), white blood cell (r = −0.436, p < 0.05), platelet (r = −0.431, p < 0.05), and reticulocyte (r = −0.447, p < 0.05). The phagocytosis of mDC does not correlate with the response to IST.ConclusionsThe increased phagocytosis of mDC in untreated SAA patients may contribute to abnormal activation of T helper (Th) and subsequent cytotoxic T lymphocyte (CTL) activation in these patients. It may be involved in the immune pathogenesis of SAA.     

Circulating brain‐derived neurotrophic factor dysregulation and its linkage with lipid level,stenosis degree,and inflammatory cytokines in coronary heart disease

BackgroundBrain‐derived neurotrophic factor (BDNF) regulates the lipid metabolism, atherosclerosis plaque formation, and inflammatory process, while the study about its clinical role in coronary heart disease (CHD) is few. The present study intended to explore the expression of BDNF and its relationship with stenosis, inflammation, and adhesion molecules in CHD patients.MethodsAfter serum samples were obtained from 207 CHD patients, BDNF, tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17A, vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1) levels were determined using ELISA. Then, the BDNF level was also examined in 40 disease controls (DCs) and 40 healthy controls (HCs), separately.ResultsBDNF was lower in CHD patients than in DCs and HCs (median (95% confidential interval) value: 5.6 (3.5–9.6) ng/mL vs. 10.7 (6.1–17.0) ng/mL and 12.6 (9.4–18.2) ng/mL, both p < 0.001). BDNF could well distinguish CHD patients from DCs (area under the curve [AUC]: 0.739) and HCs (AUC: 0.857). BDNF was negatively associated with triglyceride (p = 0.014), total cholesterol (p = 0.037), and low‐density lipoprotein cholesterol (p = 0.008). BDNF was negatively associated with CRP (p < 0.001), TNF‐α (p < 0.001), IL‐1β (p = 0.008), and IL‐8 (p < 0.001). BDNF was negatively related to VCAM‐1 (p < 0.001) and ICAM‐1 (p = 0.003). BDNF was negatively linked with the Gensini score (p < 0.001).ConclusionBDNF reflects the lipid dysregulation, inflammatory status, and stenosis degree in CHD patients.     

Potential of long non‐coding RNA KCNQ1OT1 as a biomarker reflecting systemic inflammation,multiple organ dysfunction,and mortality risk in sepsis patients

BackgroundLong non‐coding RNA potassium voltage‐gated channel subfamily Q member 1 opposite strand 1 (lnc‐KCNQ1OT1) represses inflammation and multiple organ dysfunction, whereas its clinical value in sepsis is unclear. Thus, this study aimed to explore this issue.MethodsLnc‐KCNQ1OT1 from peripheral blood mononuclear cells were detected by RT‐qPCR in 116 sepsis patients and 60 healthy controls (HCs). Moreover, sepsis patients were followed‐up until death or up to 28 days.ResultsLnc‐KCNQ1OT1 decreased in patients with sepsis than in HCs (p < 0.001). In sepsis patients, lnc‐KCNQ1OT1 was negatively correlated with sequential organ failure assessment (SOFA) scores (r = −0.344, p < 0.001) and several SOFA subscale scores (including respiratory system, coagulation, liver, and renal systems) (all r < 0, p < 0.05). Furthermore, lnc‐KCNQ1OT1 was negatively correlated with CRP (r = −0.386, p < 0.001), TNF‐α (r = −0.332, p < 0.001), IL‐1β (r = −0.319, p < 0.001), and IL‐6 (r = −0.255, p = 0.006). Additionally, lnc‐KCNQ1OT1 levels were lower in sepsis deaths than in sepsis survivors (p < 0.001), and the receiver operating characteristic curve showed that lnc‐KCNQ1OT1 had an acceptable ability to predict 28‐day mortality (area under the curve: 0.780, 95% confidence interval: 0.678–0.882). Meanwhile, its ability to predict 28‐day mortality risk was higher than that of CRP, TNF‐α, IL‐1β, and IL‐6, but slightly lower than the SOFA score and acute physiology and chronic health evaluation II score.ConclusionLnc‐KCNQ1OT1 serves as a potential biomarker for monitoring disease severity and prognosis in patients with sepsis.     

Kallistatin treatment attenuates lethality and organ injury in mouse models of established sepsis

IntroductionKallistatin levels in the circulation are reduced in patients with sepsis and liver disease. Transgenic mice expressing kallistatin are resistant to lipopolysaccharide (LPS)-induced mortality. Here, we investigated the effect of kallistatin on survival and organ damage in mouse models of established sepsis.MethodsMice were rendered septic by cecal ligation and puncture (CLP), or endotoxemic by LPS injection. Recombinant human kallistatin was administered intravenously six hours after CLP, or intraperitoneally four hours after LPS challenge. The effect of kallistatin treatment on organ damage was examined one day after sepsis initiation, and mouse survival was monitored for four to six days.ResultsHuman kallistatin was detected in mouse serum of kallistatin-treated mice. Kallistatin significantly reduced CLP-induced renal injury as well as blood urea nitrogen, serum creatinine, interleukin-6 (IL-6), and high mobility group box-1 (HMGB1) levels. In the lung, kallistatin decreased malondialdehyde levels and HMGB1 and toll-like receptor-4 (TLR4) synthesis, but increased suppressor of cytokine signaling-3 (SOCS3) expression. Moreover, kallistatin attenuated liver injury, serum alanine transaminase (ALT) levels and hepatic tumor necrosis factor-α (TNF-α) synthesis. Furthermore, delayed kallistatin administration improved survival in CLP mice by 38%, and LPS-treated mice by 42%. In LPS-induced endotoxemic mice, kallistatin attenuated kidney damage in association with reduced serum creatinine, IL-6 and HMGB1 levels, and increased renal SOCS3 expression. Kallistatin also decreased liver injury in conjunction with diminished serum ALT levels and hepatic TNF-α and TLR4 expression. In cultured macrophages, kallistatin through its active site increased SOCS3 expression, but this effect was blocked by inhibitors of tyrosine kinase, protein kinase C and extracellular signal-regulated kinase (ERK), indicating that kallistatin stimulates a tyrosine-kinase-protein kinase C-ERK signaling pathway.ConclusionsThis is the first study to demonstrate that delayed human kallistatin administration is effective in attenuating multi-organ injury, inflammation and mortality in mouse models of polymicrobial infection and endotoxemia. Thus, kallistatin therapy may provide a promising approach for the treatment of sepsis in humans.     

GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice

ObjectiveG protein-coupled receptor 43 (GPR43), a receptor for short-chain fatty acids, plays a role in suppressing tumor growth; however, the detailed underlying mechanism needs to be comprehensively elucidated. In this study, we investigated the role of GPR43 in inhibiting tumor growth using Apc^Min/+, a murine model of intestinal tumors.Materials and MethodsUsing GPR43^−/− Apc^Min/+ and GPR43^+/− Apc^Min/+ mice, the number of tumors was analyzed at the end of the experimental period. Immunohistochemistry, quantitative polymerase chain reaction, and Western blotting were performed to analyze cellular proliferation and proliferation-associated signal pathways.ResultsOur results revealed that GPR43 deficiency resulted in increased tumor numbers in Apc^Min/+ mice. Ki67 was highly expressed in GPR43^−/− mice (p > 0.05). Increased expression levels of proinflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, and amino acid transporters were not observed in GPR43-deficient mice compared to GPR43-sufficient mice. Furthermore, GPR43-deficient tumor tissues showed enhanced mammalian target of rapamycin-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p > 0.05) and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p > 0.05), but not Akt (protein kinase B) phosphorylation (p = 0.7088).ConclusionCollectively, GPR43 affords protection against tumor growth at least partly through inhibition of the mammalian target of rapamycin complex 1 pathway.     

Inter‐alpha‐trypsin inhibitor heavy chain 4: A serologic marker relating to disease risk,activity, and treatment outcomes of rheumatoid arthritis

ObjectiveInter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA.MethodsAfter the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA.ResultsITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (r_s  = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (r_s  = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (r_s  = −0.337, p = 0.001), IL‐6 (r_s  = −0.221, p = 0.033), and IL‐17A (r_s  = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (r_s  = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05).ConclusionCirculating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.     

LncRNA UCA1, miR‐26a,and miR‐195 in coronary heart disease patients: Correlation with stenosis degree,cholesterol levels,inflammatory cytokines,and cell adhesion molecules

BackgroundLong noncoding RNA urothelial cancer‐associated 1 (lnc‐UCA1) targets microRNA‐26a (miR‐26a) and microRNA‐195 (miR‐195) to participate in coronary heart disease (CHD) progression via regulation of vascular smooth muscle cell and microvascular endothelial cell viability and mobility. Therefore, this study set out to further explore the relationship between lnc‐UCA1 and miR‐26a and miR‐195, along with their roles in the management of patients with CHD.MethodsOne hundred and thirty‐six CHD patients and 70 age‐/gender‐matched controls were recruited in this case‐control study. Their peripheral blood mononuclear cell samples were collected for lnc‐UCA1, miR‐26a, and miR‐195 measurement. Furthermore, serum samples from CHD patients were obtained for inflammatory cytokines and cell adhesion molecules measurement. The Gensini score was used to evaluate the stenosis severity in CHD patients.ResultsLnc‐UCA1 expression tend to be increased, while miR‐26a and miR‐195 expressions were reduced in patients with CHD compared to that of controls (all p < 0.001). In CHD patients, lnc‐UCA1 was negatively correlated with miR‐26a (p < 0.001) and miR‐195 (p = 0.014). Besides, lnc‐UCA1 was positively correlated with Gensini score (p < 0.001), total cholesterol (p = 0.019), low‐density lipoprotein cholesterol (p = 0.002), and C‐reactive protein (p < 0.001), while miR‐26a (p < 0.001) and miR‐195 (p = 0.002) were negatively correlated with Gensini score. What''s more, lnc‐UCA1 was positively correlated with tumor necrosis factor (TNF)‐α (p = 0.004), interleukin (IL)‐1β (p = 0.041), vascular cell adhesion molecule‐1 (VCAM‐1) (p = 0.010), and intercellular adhesion molecule‐1 (ICAM‐1) (p < 0.001). While miR‐26a was negatively correlated with some of the individual inflammatory cytokines and cell adhesion molecules.ConclusionLnc‐UCA1, miR‐26a, and miR‐195 may serve as potential biomarkers for CHD management.     

Physician Enabling Skills Questionnaire: Validation d’un outil récemment développé en contexte de soins primaires

ObjectiveTo evaluate the reliability and validity of the newly developed Physician Enabling Skills Questionnaire (PESQ) by assessing its internal consistency, test-retest reliability, concurrent validity with patient-centred care, and predictive validity with patient activation and patient enablement.DesignValidation study.SettingSaguenay, Que.ParticipantsOne hundred patients with at least 1 chronic disease who presented in a waiting room of a regional health centre family medicine unit.ResultsThe internal consistency of the 6 subscales of the PESQ was adequate (Cronbach α = .69 to .92). The test-retest reliability was very good (r = 0.90; 95% CI 0.84 to 0.93). Concurrent validity with the Patient Perception of Patient-Centredness instrument was good (r = −0.67; 95% CI −0.78 to −0.53; P < .001). The PESQ accounts for 11% of the total variance with the Patient Activation Measure (r² = 0.11; P = .002) and 19% of the variance with the Patient Enablement Instrument (r² = 0.19; P < .001).ConclusionThe newly developed PESQ presents good psychometric properties, allowing for its use in practice and research.     

Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

IntroductionTranexamic acid (TXA) is the standard medication to prevent or treat hyperfibrinolysis. However, prolonged inhibition of lysis (so-called “fibrinolytic shutdown”) correlates with increased mortality. A new viscoelastometric test enables bedside quantification of the antifibrinolytic activity of TXA using tissue plasminogen activator (TPA).Materials and MethodsTwenty-five cardiac surgery patients were included in this prospective observational study. In vivo, the viscoelastometric TPA test was used to determine lysis time (LT) and maximum lysis (ML) over 96 h after TXA bolus. Additionally, plasma concentrations of TXA and plasminogen activator inhibitor 1 (PAI-1) were measured. Moreover, dose effect curves from the blood of healthy volunteers were performed in vitro. Data are presented as median (25–75th percentile).ResultsIn vivo TXA plasma concentration correlated with LT (r = 0.55; p < 0.0001) and ML (r = 0.62; p < 0.0001) at all time points. Lysis was inhibited up to 96 h (LT_TPA-test: baseline: 398 s [229–421 s] vs. at 96 h: 886 s [626–2,175 s]; p = 0.0013). After 24 h, some patients (n = 8) had normalized lysis, but others (n = 17) had strong lysis inhibition (ML <30%; p < 0.001). The high- and low-lysis groups differed regarding kidney function (cystatin C: 1.64 [1.42–2.02] vs. 1.28 [1.01–1.52] mg/L; p = 0.002) in a post hoc analysis. Of note, TXA plasma concentration after 24 h was significantly higher in patients with impaired renal function (9.70 [2.89–13.45] vs.1.41 [1.30–2.34] µg/mL; p < 0.0001). In vitro, TXA concentrations of 10 µg/mL effectively inhibited fibrinolysis in all blood samples.ConclusionsDetermination of antifibrinolytic activity using the TPA test is feasible, and individual fibrinolytic capacity, e.g., in critically ill patients, can potentially be measured. This is of interest since TXA-induced lysis inhibition varies depending on kidney function.     

The relation of common inflammatory cytokines with anxiety and depression and their values in estimating cardiovascular outcomes in coronary heart disease patients

BackgroundInflammatory cytokines are associated with the occurrence and severity of psychological disorders in cerebro‐cardiovascular disease patients. This study aimed to investigate the correlation of inflammatory cytokines with anxiety and depression in coronary heart disease (CHD) patients and their values for estimating cardiovascular outcomes.MethodsTotally, 150 CHD patients and 50 healthy subjects were enrolled. Then, tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, IL‐10, and IL‐17 in their serum samples were detected using ELISA assay; anxiety and depression were assessed by the HADS score. For CHD patients, major adverse cardiac events (MACE) were recorded and evaluated.ResultsCHD patients presented with increased TNF‐α (median: 50.0 vs. 37.0 pg/ml, p < 0.001), IL‐1β (median: 2.7 vs. 2.0 pg/ml, p < 0.001), IL‐6 (median: 24.7 vs. 24.3 pg/ml, p = 0.032), IL‐17A (median: 58.6 vs. 43.6 pg/ml, p < 0.001), HADS‐A score (p < 0.001), HADS‐D score (p < 0.001), anxiety rate (p < 0.001), and depression rate (p < 0.001) compared to healthy subjects. Then, TNF‐α (p = 0.003), IL‐1β (p = 0.023), and IL‐17A (p < 0.001) were related to elevated HADS‐A score. Also, TNF‐α (p = 0.014) and IL‐17A (p = 0.020) positively, while IL‐10 (p = 0.047) negatively related to the HADS‐D score in CHD patients. Interestingly, elevated TNF‐α and IL‐17A were associated with anxiety and depression occurrence in CHD patients (all p < 0.05). Inspiringly, only TNF‐α high, but not other cytokines, was related to elevated accumulating MACE (p = 0.041), while no correlation of anxiety (p = 0.173) or depression (p = 0.068) with accumulating MACE was observed.ConclusionTNF‐α and IL‐17A correlate with anxiety and depression, while only TNF‐α high is related to elevated accumulating MACE in CHD patients.     

Clinical value of serum JKAP in acute ischemic stroke patients

BackgroundJun N‐terminal kinase pathway‐associated phosphatase (JKAP) regulates neuronal function, T helper (Th) 1/2/17 cell differentiation, and inflammatory process, but its clinical role in acute ischemic stroke (AIS) patients remains unclear. Hence, this study intended to evaluate JKAP level and its relationship with disease severity, Th1, 2, 17 secreted cytokines, adhesion molecules, and prognosis of AIS patients.MethodsSerum JKAP of 122 AIS patients and 50 controls was detected by ELISA. For AIS patients only, Th1, 2, 17 secreted cytokines IFN‐γ, IL‐4, IL‐17; TNF‐α, ICAM‐1, and VCAM‐1 were also detected by ELISA.ResultsJKAP was decreased in AIS patients compared with controls (46.350 (interquartile range (IQR): 34.250–59.875) pg/ml vs. 84.500 (IQR: 63.175–113.275) pg/ml, p < 0.001), which could distinguish AIS patients from controls (area under curve (AUC): 0.810, 95% confidence interval (CI): 0.732–0.888). In AIS patients, JKAP negatively linked with the National Institutes of Health Stroke Scale (NIHSS) score (r_s  = −0.342, p < 0.001); besides, it was positively related to IL‐4 (r_s  = 0.213, p = 0.018) and negatively associated with IL‐17 (r_s  = −0.270, p = 0.003) but not related to IFN‐γ (r_s  = −0.146, p = 0.109). Furthermore, elevated JKAP associated with declined TNF‐α (r_s  = −0.219, p = 0.015) and ICAM‐1 (r_s  = −0.235, p = 0.009) but not related to VCAM‐1 (r_s  = −0.156, p = 0.085). Besides, declined JKAP was linked with 2‐year recurrence (p = 0.027) and 3‐year recurrence (p = 0.010) in AIS patients; while JKAP was not related to 1‐year recurrence or death risk (both p > 0.050).ConclusionJKAP may sever as a candidate prognostic biomarker in AIS patients, indicating its potency for AIS management.     

Hyperglucagonemia Does Not Explain the β-Cell Hyperresponsiveness and Insulin Resistance in Dysglycemic Youth Compared With Adults: Lessons From the RISE Study

OBJECTIVETo determine whether β-cell hyperresponsiveness and insulin resistance in youth versus adults in the Restoring Insulin Secretion (RISE) Study are related to increased glucagon release.RESEARCH DESIGN AND METHODSIn 66 youth and 350 adults with impaired glucose tolerance (IGT) or recently diagnosed type 2 diabetes (drug naive), we performed hyperglycemic clamps and oral glucose tolerance tests (OGTTs). From clamps we quantified insulin sensitivity (M/I), plasma fasting glucagon and C-peptide, steady-state glucagon and C-peptide at glucose of 11.1 mmol/L, and arginine-stimulated glucagon (acute glucagon response [AGR]) and C-peptide (ACPRmax) responses at glucose >25 mmol/L.RESULTSMean ± SD fasting glucagon (7.63 ± 3.47 vs. 8.55 ± 4.47 pmol/L; P = 0.063) and steady-state glucagon (2.24 ± 1.46 vs. 2.49 ± 1.96 pmol/L, P = 0.234) were not different in youth and adults, respectively, while AGR was lower in youth (14.1 ± 5.2 vs. 16.8 ± 8.8 pmol/L, P = 0.001). Significant age-group differences in insulin sensitivity, fasting C-peptide, steady-state C-peptide, and ACPRmax were not related to glucagon. Fasting glucose and glucagon were positively correlated in adults (r = 0.133, P = 0.012) and negatively correlated in youth (r = −0.143, P = 0.251). In both age-groups, higher fasting glucagon was associated with higher fasting C-peptide (youth r = 0.209, P = 0.091; adults r = 0.335, P < 0.001) and lower insulin sensitivity (youth r = −0.228, P = 0.066; adults r = −0.324, P < 0.001). With comparable fasting glucagon, youth had greater C-peptide and lower insulin sensitivity. OGTT suppression of glucagon was greater in youth.CONCLUSIONSYouth with IGT or recently diagnosed type 2 diabetes (drug naive) have hyperresponsive β-cells and lower insulin sensitivity, but their glucagon concentrations are not increased compared with those in adults. Thus, α-cell dysfunction does not appear to explain the difference in β-cell function and insulin sensitivity in youth versus adults.     

Th17, rather than Th1 cell proportion,is closely correlated with elevated disease severity,higher inflammation level,and worse prognosis in sepsis patients

ObjectiveThe current study aimed to investigate the prognostic value of T helper (Th) 1 and Th17 proportions in sepsis patients.MethodsTh1 and Th17 cells in blood CD4⁺ T cells were detected by flow cytometry in 210 sepsis patients and 100 healthy controls (HCs). Besides, serum interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), and interleukin‐17 (IL‐17) levels in the enrolled sepsis patients were determined with enzyme‐linked immunosorbent assay.ResultsCompared with HCs, Th1 and Th17 proportions were elevated in sepsis patients (both p < .001). Meanwhile, Th1 proportion was strongly correlated with IFN‐γ (p < .001, r = .484) but weakly correlated with TNF‐α (p = .024, r = .156) and IL‐17 (p = .002, r = .212), while Th17 proportion showed faint correlation with IFN‐γ (p = .015, r = .168), but strong correlations with TNF‐α (p < .001, r = .602) and IL‐17 (p < .001, r = .498) in sepsis patients. Besides, Th1 proportion was weakly associated with APACHE II score (p = .030, r = .150), but Th17 proportion was closely associated with APACHE II score (p < .001, r = .322) and SOFA score (p < .001, r = .337) in sepsis patients. Regarding their prognostic value, Th1 proportion (p = .042) was slightly, while Th17 proportion (p < .001) was dramatically, increased in septic deaths compared with survivors, and Th17 possessed good predictive value for 28‐day mortality risk (AUC: 0.748, 95% CI: 0.659–0.836).ConclusionTh1 and Th17 proportions are elevated in sepsis patients compared with HCs, and Th17 proportion is correlated with increased disease severity, higher inflammation level, and worse prognosis in sepsis patients.     

Real‐life effectiveness of biological therapies on symptoms in severe asthma with comorbid CRSwNP

BackgroundWe aimed to evaluate the effectiveness of different antibody therapies on nasal polyp symptoms in patients treated for severe asthma.MethodsWe performed a retrospective analysis of patients with severe asthma and comorbid CRSwNP who were treated with anti‐IgE, anti‐IL‐5/R or anti‐IL‐4R. CRSwNP symptom burden was evaluated before and after 6 months of therapy.ResultsFifty patients were included hereof treated with anti‐IgE: 9, anti‐IL‐5/R: 26 and anti‐IL‐4R: 15 patients. At baseline median SNOT‐20 was similar among groups (anti‐IgE: 55, anti‐IL‐5/R: 52 and anti‐IL‐4R: 56, p = 0.76), median visual analogue scale (VAS) for nasal symptoms was 4, 7 and 8 (p = 0.14) and VAS for total symptoms was higher in the anti‐IL‐4R group (4, 5 and 8, p = 0.002). After 6 months SNOT‐20 improved significantly in all patient groups with median improvement of anti‐IgE: −8 (p < 0.01), anti‐IL‐5/R: −13 (p < 0.001) and anti‐IL‐4R: −18 (p < 0.001), with larger improvement in the anti‐IL‐4R group than in anti‐IgE (p < 0.001) and anti‐IL‐5/R (p < 0.001) groups. VAS nasal symptoms improved by median anti‐IgE: 0 (n.s.), anti‐IL‐5/R: −1 (p < 0.01) and anti‐IL‐4R: −3 (p < 0.001), VAS total symptoms by anti‐IgE: −1 (n.s.), anti‐IL‐5/R: −2 (p < 0.001) and anti‐IL‐4R: −2 (p < 0.001).ConclusionsTreatment by all antibodies showed effectiveness in reducing symptoms of CRSwNP in patients with severe asthma, with the largest reduction observed in anti‐IL‐4R‐treated patients.     

Diagnosis of Neuropathy and Risk Factors for Corneal Nerve Loss in Type 1 and Type 2 Diabetes: A Corneal Confocal Microscopy Study

OBJECTIVETo assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss.RESEARCH DESIGN AND METHODSA total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.RESULTSCorneal nerve fiber density (CNFD) (P < 0.0001 and P < 0.0001), corneal nerve fiber branch density (CNBD) (P < 0.0001 and P < 0.0001), and corneal nerve fiber length (CNFL) (P < 0.0001 and P = 0.02) were significantly lower in patients with type 1 and type 2 diabetes compared with control subjects. CNFD (P < 0.0001), CNBD (P < 0.0001), and CNFL (P < 0.0001) were lower in type 1 diabetes compared with type 2 diabetes. Receiver operating characteristic curve analysis for the diagnosis of DPN demonstrated a good area under the curve for CNFD of 0.81, CNBD of 0.74, and CNFL of 0.73. Multivariable regression analysis showed a significant association among reduced CNFL with age (β = −0.27, P = 0.007), HbA_1c (β = −1.1; P = 0.01), and weight (β = −0.14; P = 0.03) in patients with type 2 diabetes and with duration of diabetes (β = −0.13; P = 0.02), LDL cholesterol (β = 1.8, P = 0.04), and triglycerides (β = −2.87; P = 0.009) in patients with type 1 diabetes.CONCLUSIONSCCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes.