Severity and Patterns of Blood-Nerve Barrier Breakdown in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Correlations with Clinical Subtypes

Objective

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype.

Methods

We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs).

Results

The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion.

Conclusions

Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes.     

Elevated Vibration Perception Thresholds in CIDP Patients Indicate More Severe Neuropathy and Lower Treatment Response Rates

Introduction

Vibration perception threshold (VPT) examination using a neurothesiometer provides objective, sensitive and specific information, and has been utilized mainly in patients with diabetic polyneropathy.

Objectives

Explore the utility of VPT examination in CIDP patients.

Methods

CIDP subjects attending the Neuromuscular clinic between 01/2013 and 12/2014 were evaluated. Demographic data, clinical history, physical examination, VPT values, and electrophysiologic data from their charts were extracted.

Results

70 charts were reviewed. 55 CIDP patients had elevated VPT, associated with higher frequency of abnormal sensory testing for various modalities (92.7% vs. 46.7%, p<0.0001), lower sensory and motor amplitudes and reduced conduction velocities on nerve conduction studies, and lower treatment response rates (54% vs. 93%, p = 0.01).

Conclusion

VPT examination is a simple tool, which is a reliable and sensitive measure not only for diabetic neuropathy, but also for CIDP. Moreover, in CIDP, elevated VPT values are also associated with lower treatment response rates.     

Live Birth and Cumulative Live Birth Rates in Expected Poor Ovarian Responders Defined by the Bologna Criteria Following IVF/ICSI Treatment

ObjectiveTo determine the live birth and cumulative live birth rates of expected poor ovarian responders according to the Bologna criteria and to compare their outcomes with those of expected normal respondersDesignRetrospective analysisSettingUniversity infertility clinicPatientsA total of 1,152 subfertile women undergoing their first in vitro fertilization (IVF) cycleInterventionsWomen were classified into 4 groups according to the Bologna criteria for comparisonResultsWomen with expected poor response (POR) had the lowest live birth rate than the other 3 groups (23.8%, p = 0.031). Cumulative live birth rates were significantly lower in those with expected POR than those with expected normal ovarian response (NOR) (35.8% vs 62.8%, p<0.0001). In the subgroup analysis, the cumulative live birth rates in expected PORs were significantly lower in those who had ≤3 oocytes retrieved (18.6% for ≤3 oocytes vs 44.0% for >3 oocytes, p = 0.006) whereas the live birth rates in fresh cycle did not differ (17.8% vs 30.9%, p = 0.108).ConclusionWomen who were expected POR according to the Bologna criteria had lower live birth and cumulative live birth than expected NOR but they still can achieve reasonable treatment outcomes and IVF treatment should not be precluded.     

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

IntroductionDiabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN’s three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study’s main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM.ResultsThe presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001) and SLS time (9.3 vs. 10.3 seconds; p = 0.003) respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002) and FES-I score (38 vs. 33 points; p = 0.034). The MNSI score was reverse and significantly correlated with both BBS score (Spearman’s r = -0.479; p<0.001) and SLS time (Spearman’s r = -0.169; p = 0.017). In the multivariate regression model, we observed that patient’s age, DN severity and depression’s symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM.ConclusionsThe presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.     

Vitamin D Deficiency—Prognostic Marker or Mortality Risk Factor in End Stage Renal Disease Patients with Diabetes Mellitus Treated with Hemodialysis—A Prospective Multicenter Study

BackgroundEnd stage renal disease (ESRD) patients on renal replacement therapy (RRT) with diabetes mellitus (DM) have a higher mortality rate and an increase prevalence of vitamin D deficiency compared to those without DM. It is still debated if vitamin D deficiency is a risk factor or a prognostic marker for mortality in these patients. This study investigated the prevalence of vitamin D deficiency and its impact on all-cause mortality in HD patients with DM.MethodsOur prospective non-interventional cohort study included 600 patients on hemodialysis therapy (HD) (median aged 56, interquartile range (19) years, 332 (55.3%) males) recruited from 7 HD centers, from all main geographical regions of Romania. The prevalence of DM was 15.3%. They were then followed regarding: dialysis duration, dialysis efficiency, renal anemia, CKD-MBD, inflammatory status and comorbidities: coronary artery disease (CAD), peripheral vascular disease (PVD) and stroke. The deficiency of 25-OH vitamin D was defined as a value lower than12 ng/mL.ResultsPatients were followed for 3 years. The overall 3 year mortality was 25.5% (153 individuals), being higher in patients with DM as compared to those without DM (33.7% vs. 24.0%; P = 0.049). The time-related prognosis was also influenced by the presence of DM, at the survival analysis resulting in a HR of 1.52 [1.03 to 2.26] 95% CI, P = 0.037, for death in dialyzed patients with DM. In DM patients, 25-OH vitamin D deficiency was significantly higher (37.0% compared to 24.0%, P = 0.009). Furthermore, in patients with DM we observed a shorter dialysis duration (2 vs. 3 years, P<0.001) and a lower intact parathyroid hormone (iPTH) (258.0 pg/ml vs. 441.9 pg/ml, P = 0.002). Regarding the presence of comorbidities at the inclusion in the study, the presence of diabetes in dialyzed patients was associated with increased prevalence of CAD (87.0% vs. 58.1%, P<0.001), PVD (67.4% vs. 17.3%, P<0.001) and history of stroke (29.3% vs. 14.0%, P<0.001). In patients with DM the presence of 25-OH vitamin D deficiency increased the probability of death (50.0% vs. 24.1%; P = 0.011). In multiple Cox proportional hazards analysis, vitamin D deficiency remained an independent predictor for mortality in dialysis patients with DM (HR = 1.71, 95% CI 1.21 to 2.43, P = 0.003). In the same time, multiple Cox proportional hazards analysis showed that age (HR = 1.02 per one year increase, P = 0.004), CAD (HR = 1.55, P = 0.046) and PVD (HR = 1.50, P = 0.029) were independent predictors for mortality in dialysis patients with DM.ConclusionsESRD patients with DM treated with HD have a higher overall mortality than non-DM patients. Vitamin D deficiency is significantly more prevalent in HD patients with DM. Low 25-OH vitamin D levels were associated with increased all-cause mortality in these patients. According to our data, in HD patients with DM, screening for vitamin D deficiency (and its correction) should be mandatory for an optimal risk reduction strategy.     

Adding Rapid-Acting Insulin or Glp-1 Receptor Agonist to Basal Insulin: Outcomes in A Community Setting

ObjectiveTo evaluate real-world outcomes in patients with type 2 diabetes mellitus (T2DM) receiving basal insulin who initiate add-on therapy with a rapid-acting insulin (RAI) or a glucagon-like peptide 1 (GLP-1) receptor agonist.MethodsData were extracted retrospectively from a U.S. health claims database. Adults with T2DM on basal insulin who added an RAI (basal + RAI) or GLP-1 receptor agonist (basal + GLP-1) were included. Propensity score matching (with a 1 up to 3 ratio) was used to control for differences in baseline demographics, clinical characteristics, and health resource utilization. Endpoints included prevalence of hypoglycemia, pancreatic events, all-cause and diabetes-related resource utilization, and costs at 1-year follow-up.ResultsOverall, 6,718 matched patients were included: 5,013 basal + RAI and 1,705 basal + GLP1. Patients in both groups experienced a similar proportion of any hypoglycemic event (P = .4079). Hypoglycemic events leading to hospitalization were higher in the basal + RAI cohort (2.7% vs. 1.8%; P = .0444). The basal + GLP-1 cohort experienced fewer all-cause (13.55% vs. 18.61%; P < .0001) and diabetes-related hospitalizations (11.79% vs. 15.68%; P < .0001). The basal + GLP-1 cohort had lower total all-cause health care costs ($18,413 vs. $20,821; P = .0002) but similar diabetes-related costs ($9,134 vs. $8,985; P < .0001) compared with the basal + RAI cohort.ConclusionsAdd-on therapy with a GLP-1 receptor agonist in T2DM patients receiving basal insulin was associated with fewer hospitalizations and lower total all-cause costs compared with add-on therapy using an RAI and could be considered as an alternative to an RAI in certain patients with T2DM who do not achieve effective glycemic control with basal insulin. (Endocr Pract. 2015; 21:68-76)     

Identifying Risk Factors for Severe Hypoglycemia in Hospitalized Patients with Diabetes

ObjectiveSome of the deleterious effects of hypoglycemia in hospitalized patients include increased rates of mortality and longer length of stay. Our primary objective was to identify the risk factors associated with severe hypoglycemia to identify those patients at highest risk.MethodsThe medical records of 5,026 patients with diabetes mellitus (DM) admitted in 2010 were reviewed to identify those patients that developed severe hypoglycemia (blood glucose [BG] < 40 mg/dL). We performed c2 tests to assess statistical significance. Adjusted logical regression was used to determine the risk factors for hypoglycemia in the hospital.ResultsOut of 5,026 DM patients included in our review, 81 experienced severe hypoglycemia (1.6%). Statistically higher proportions of chronic kidney disease (CKD; 69.1% vs. 46.9%, P < .001), congestive heart failure (CHF; 48.1% vs. 28.5%, P < .001), sepsis (49.4% vs. 12.5%, P < .001), insulin use (45.7% vs. 26.04%, P = .000), type 1 DM (21% vs. 5.1%, P = .000), and cirrhosis (14.8% vs. 7.2%, P = .009) were seen in the severe hypoglycemic group compared to the nonsevere hypoglycemic group. Overall, 84% of patients who experienced an episode of severe hypoglycemia in the hospital (BG < 40 mg/dL) had a previous episode of hypoglycemia (BG < 70 mg/dL). The odds ratios (ORs) for type 1 DM, sepsis, previous hypoglycemia, and insulin use were 3.43 (95% confidence interval [CI] 1.81, 6.49), 2.64 (95% CI 1.6, 4.35), 46.1 (95% CI 24.76, 85.74), and 1.66 (95% CI 1.02, 2.69), respectively.ConclusionPrior episodes of hypoglycemia in the hospital, the presence of type 1 DM, insulin use, and sepsis were identified as independent risk factors for the development of severe hypoglycemia in the hospital. (Endocr Pract. 2014;20:1051-1056)     

Glycemic Control and Diabetic Dyslipidemia in Adolescents with Type 2 Diabetes

ObjectiveThe incidence of type 2 diabetes mellitus (T2DM) is increasing at an alarming rate, especially in ethnic minorities, and T2DM is associated with significant comorbidities. The primary objective of this study was to assess glycemic control and cardiovascular risk outcomes in children with T2DM at 1 year after diagnosis. We also assessed whether insulin treatment at onset of diabetes is beneficial for overall outcome in those with elevated glycated hemoglobin (HbA1C).MethodsA retrospective electronic chart review of non-Hispanic white (NHW) and African American (AA) children with T2DM.ResultsA total of 86 patients (66.3% females, 79.1% AA, mean age, 13.8 ± 2.4 years) with T2DM were included. Analyses of therapeutic outcome measures at the 1-year follow-up showed HbA1C <8% in 27.7% of patients, low-density-lipoprotein cholesterol (LDL-C) >130 mg/dL in 12.5%, non-high-density-lipoprotein cholesterol (non-HDL-C) >160 mg/dL in 15.6%, HDL-C <35 mg/dL in 25%, systolic hypertension (HTN) in 35.6%, and diastolic HTN in 6.8% of subjects. Among those started on insulin at initial diagnosis, there was significant improvement in glycemic outcomes (P<.0001 on insulin vs. P = .02 not on insulin) and dyslipidemia (total cholesterol [TC] [P = .001], LDL-C [P = .02], HDL-C [P = .01], non-HDL-C [P = .0002], and TC/HDL-C [P = .005]) compared with no significant change among those who did not receive insulin at diagnosis.ConclusionSubstantial numbers of children with T2DM do not achieve glycemic and cardiovascular therapeutic goals 1 year after diagnosis. Insulin therapy at diagnosis has significant beneficial effects on diabetic dyslipidemia in those with higher HbA1C. (Endocr Pract. 2013; 19:972-979)     

Hematopoietic stem cell transplantation for uncommon immune-mediated neurological disorders: A literature review

BackgroundChronic inflammatory demyelinating polyneuropathy (CIDP), stiff-person syndrome (SPS), neuromyelitis optica spectrum disorders (NMOSD) and severe refractory myasthenia gravis (MG) are immune-mediated neurological diseases that severely affect patients’ functionality and quality of life, with a considerable percentage undergoing relapse or not responding to conventional treatment options. Autologous hematopoietic stem cell transplantation (auto-HSCT) has emerged as a potential second-line treatment alternative.MethodsWe performed a literature review in PubMed/Medline, EMBASE, Web of Science and Cochrane Library from inception to September 2021 of reported cases and studies of CIDP, SPS, NMOSD and MG that underwent HSCT as a treatment option.ResultsA total of 173 patients who underwent HSCT were found, including 32 patients described in case reports and 60 in a phase 2 clinical trial with CIDP, 29 patients with SPS, 42 patients with NMOSD and 10 patients with refractory MG. Complete remission was documented in 68/92 patients with CIDP, 13/29 with SPS and 10/10 with MG. From the NMOSD cases, 24/42 were relapse-free at last follow-up, with 13/33 having negative anti-AQ4 antibodies after HSCT. From all the included studies, only 8/173 patients received an allogeneic HSCT, 4/8 after a failed auto-HSCT. All showed clinical improvement and disease remission.ConclusionHSCT has the potential to induce long-term remission in patients with CIDP, NMOSD, SPS or MG with adequate safety and tolerability. Collaboration between centers is needed to implement larger, homogeneous prospective studies, focusing on immunological correlates of favorable long-term response.     

Association between Polymorphisms in Vascular Endothelial Growth Factor Gene and Response to Chemotherapies in Colorectal Cancer: A Meta-Analysis

BackgroundSome studies have investigated the effects of polymorphisms in the vascular endothelial growth factor (VEGF) gene on responsiveness to chemotherapy for colorectal cancer (CRC) and have shown inconclusive results.MethodsEligible studies that assessed the associations between polymorphisms in the VEGF gene and response to chemotherapy in CRC were searched in the PubMed, Embase and Medline databases until November 2014. Odds ratios (OR) and 95% confidence intervals (CIs) were used to evaluate the associations, using Review Manager software, version 5.3. Stratified analysis was also conducted.ResultsIn the overall analysis, a significant association with responsiveness to chemotherapy in CRC was identified in CC vs. CA of the VEGF -2578 C/A polymorphism (OR = 1.40, 95% CI 1.00-1.97, P = 0.05) and in CC+CT vs. TT of the VEGF -460 C/T polymorphism (OR = 0.71, 95% CI 0.53-0.96, P = 0.02). In subgroup analysis, a significant association was found in excluding anti-angiogenic agent subgroup in three comparison models of the VEGF -2578 C/A polymorphism and another three genetic models of the VEGF -460 C/T C/A polymorphism.ConclusionsCC vs. CA of the VEGF -2578 C/A polymorphism and CC+CT vs. TT of the VEGF -460 C/T polymorphism might be predictive factors of responsiveness to chemotherapy in CRC. However, single-nucleotide polymorphisms in the VEGF gene lacked sufficient predictive ability to determine whether patients with CRC should add anti-angiogenic agents to their chemotherapy regimens.     

Comparison of Profile of Primary Hyperparathyroidism With and Without Type 2 Diabetes Mellitus: Retrospective Analysis From the Indian Primary Hyperparathyroidism Registry

ObjectiveTo describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM).MethodsWe conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index–matched patients with PHPT without T2DM (in 1:2 ratio).ResultsOf the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06).ConclusionThe prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening.     

亚麻木酚素对2型糖尿病小鼠学习记忆的影响及其机制初探

目的:研究亚麻木酚素(Flax ligands,FL)对2型糖尿病模型小鼠空间学习记忆的影响及其初步机制。方法:雄性C57小鼠随机分为对照组(Con)、糖尿病模型组(DM)及亚麻木酚素治疗组(DM+FL),DM与DM+FL组给予高脂饮食加小剂量链脲佐菌素(Streptozotocin,STZ)诱导2型糖尿病模型,之后DM+FL组灌胃给予FL 10 mg/kg,每日一次,连续14天,Con与DM组给予等量生理盐水。通过新物体识别试验、Morris水迷宫试验检测小鼠的学习记忆能力,利用Western blot技术测定小鼠海马脑源性神经营养因子(BDNF)及谷酰胺AMPA受体845位磷酸化(pGluA1-Ser845)蛋白表达水平。结果:与Con组比较,DM组小鼠新物体识别指数显著下降(P<0.01),在Morris水迷宫中逃避潜伏期延长(P<0.05),在目的象限内徘徊时间减少(P<0.01);小鼠海马区BDNF和pGluA1-Ser845的蛋白表达水平均显著低于对照组(P<0.01)。与DM组相比,DM+FL组小鼠新物体识别指数显著提高(P<0.01),在Morris水迷宫中逃避潜伏期明显缩短(P<0.05),目的象限徘徊时间显著增多(P<0.05);小鼠海马区BDNF和pGluA1-Ser845的蛋白表达水平均显著升高(P<0.01)。结论:亚麻木酚素对2型糖尿病小鼠学习记忆有明确改善作用,增加海马BDNF和pGlu-A1-Ser845的表达可能是其潜在作用机制。     

烟酰胺核糖抑制db/db小鼠糖尿病心肌病的作用及机制研究

目的:探讨烟酰胺核糖(NR)对2型糖尿病小鼠心肌病的治疗作用及其机制。方法:2型糖尿病模型db/db鼠和及其严格对照小鼠db/+小鼠,将小鼠分为Con (db/+)组,DM (db/db)组,DM+NR组。采用超声测小鼠心脏功能,western-blot及免疫组化测SIRT1表达含量,DHE染色、MDA含量和MnSOD活性检测反映氧化应激水平。结果:与对照组相比,db/db小鼠心脏功能显著下降(LVEF:42.3±7.2vs 73.7±10.2, P0.01;LVFS:22.1±4.2vs 42.7±6.9, P0.01),SIRT1表达量显著下调(P0.01)。NR喂养提高SIRT1表达量(P0.01),并有效改善db/db小鼠心脏功能(LVEF:53.1±8.1vs 42.3±7.2, P0.01;LVFS:33.4±6.9vs 22.1±4.2, P0.01)。同时,NR喂养显著降低了db/db小鼠心肌组织的凋亡水平和氧化应激水平(P0.05)。结论:NR有效改善了db/db小鼠的心功能障碍,降低了db/db小鼠的心肌凋亡水平和氧化应激水平,这些作用的发挥可能与NR增加SIRT1的表达量有关。     

Is neoadjuvant chemotherapy for pT2 bladder cancer associated with a survival benefit in a population-based analysis?

BackgroundPatients with organ confined muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy (RC) should receive neoadjuvant chemotherapy (CHT). However, the most contemporary CHT use rates indicate low adherence to these guidelines. We tested contemporary neoadjuvant CHT rates and associated cancer-specific mortality (CSM) and overall mortality (OM) in pT2N0 MIBC patients treated with RC.Materials and methodsWithin the SEER database (2004–2015), we identified patients with pT2N0 MIBC patients who underwent RC. CHT administration rates were evaluated using estimated annual percentage changes (EAPCs) analyses. After inverse probability of treatment weighting (IPTW), Kaplan–Meier (KM) analyses and Cox regression models (CRMs) were used to test the effect of CHT vs no CHT on survival. Landmark analyses tested for immortal time bias.ResultsOf 3978 RC patients, 38.2% of patients received CHT. Between 2004 and 2015, CHT rates increased from 15.9% to 66.2% (EAPC: +14.2%; p < 0.001). IPTW-adjusted KM showed 10-year CSM-free survival rates of 78.9% for CHT vs 76.7% for no CHT patients (p = 0.6). Similarly, IPTW-adjusted KM showed 10-year OM-free survival rates of 54.6% for CHT vs 57.9% for no CHT patients (p = 0.8). In IPTW-adjusted MCRMs, CHT was not significantly associated with lower CSM (HR 0.97, CI 0.82–1.14; p = 0.7) or OM (HR 1.02, CI 0.90–1.16; p = 0.7). Virtually the same CSM and OM rates were recorded after landmark analyses.ConclusionsCHT use in pT2N0 MIBC RC patients sharply increased over the study span. However, neoadjuvant CHT was not associated with better survival in this patient group.     

Increase in Dickkopf-1 Serum Level in Recent Spondyloarthritis. Data from the DESIR Cohort

Objectives

To investigate DKK-1 and SOST serum levels among patients with recent inflammatory back pain (IBP) fulfilling ASAS criteria for SpA and associated factors.

Methods

The DESIR cohort is a prospective, multicenter French cohort of 708 patients with early IBP (duration >3 months and <3 years) suggestive of AxSpA. DKK-1 and SOST serum levels were assessed at baseline and were compared between the subgroup of patients fulfilling ASAS criteria for SpA (n = 486; 68.6%) and 80 healthy controls.

Results

Mean SOST serum levels were lower in ASAS+ patients than healthy controls (49.21 ± 25.9 vs. 87.8 ± 26 pmol/L; p<0.0001). In multivariate analysis, age (p = 5.4 10⁻⁹), CRP level (p<0.0001) and serum DKK-1 level (p = 0.001) were associated with SOST level. Mean DKK-1 serum levels were higher in axial SpA patients than controls (30.03 ± 15.5 vs. 11.6 ± 4.2 pmol/L; p<0.0001). In multivariate analysis, DKK-1 serum levels were associated with male gender (p = 0.03), CRP level (p = 0.006), SOST serum level (p = 0.002) and presence of sacroiliitis on radiography (p = 0.05). Genetic association testing of 10 SNPs encompassing the DKK-1 locus failed to demonstrate a significant contribution of genetics to control of DKK-1 serum levels.

Conclusions

DKK-1 serum levels were increased and SOST levels were decreased among a large cohort of patients with early axial SpA compared to healthy controls. DKK-1 serum levels were mostly associated with biological inflammation and SOST serum levels.     

Statin Treatment and Mortality in Community-Dwelling Frail Older Patients with Diabetes Mellitus: A Retrospective Observational Study

Background

Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that statin treatment in older patients with DM was differentially effective across strata of mortality risk assessed by the Multidimensional Prognostic Index (MPI), based on information collected with the Standardized Multidimensional Assessment Schedule for Adults and Aged Persons (SVaMA).

Methods

In this retrospective observational study, we estimated the mortality risk in 1712 community-dwelling subjects with DM ≥ 65 years who underwent a SVaMA evaluation to establish accessibility to homecare services/nursing home admission from 2005 to 2013 in the Padova Health District, Italy. Mild (MPI-SVaMA-1), moderate (MPI-SVaMA-2), and high (MPI-SVaMA-3) risk of mortality at baseline and propensity score-adjusted hazard ratios (HR) of three-year mortality were calculated according to statin treatment.

Results

Higher MPI-SVaMA scores were associated with lower rates of statin treatment (MPI-SVaMA-1 = 39% vs MPI-SVaMA-2 = 36% vs MPI-SVaMA-3 = 24.9%. p<0.001) and higher three-year mortality (MPI-SVaMA-1 = 12.9% vs MPI-SVaMA-2 = 24% vs MPI-SVaMA-3 = 34.4%, p<0.001). After adjustment for propensity score quintiles, statin treatment was significantly associated with lower three-year mortality irrespective of MPI-SVaMA group (interaction test p = 0.303). HRs [95% confidence interval (CI)] were 0.19 (0.14–0.27), 0.28 (0.21–0.36), and 0.26 (0.20–0.34) in the MPI-SVaMA-1, MPI-SVaMA-2, and MPI-SVaMA-3 groups, respectively. Subgroup analyses showed that statin treatment was also beneficial irrespective of age. HRs (95% CI) were 0.21 (0.15–0.31), 0.26 (0.20–0.33), and 0.26 (0.20–0.35) among patients aged 65–74, 75–84, and ≥ 85 years, respectively (interaction test p=0.812).

Conclusions

Statin treatment was significantly associated with reduced three-year mortality independently of age and multidimensional impairment in community-dwelling frail older patients with DM.     

Chemoradiotherapy or chemotherapy as adjuvant treatment for resected gastric cancer: should we use selection criteria?

BackgroundThe management of gastric adenocarcinoma is essentially based on surgery followed by adjuvant treatment. Adjuvant chemotherapy (CT) as well as chemoradiotherapy (CTRT) have proven their effectiveness in survival outcomes compared to surgery alone. However, there is little data comparing the two adjuvant approaches. This study aimed to compare the prognosis and survival outcomes of patients with gastric adenocarcinoma operated and treated by adjuvant radio-chemotherapy or chemotherapyMaterials and methodsWe retrospectively evaluated 80 patients with locally advanced gastric cancer (LGC) who received adjuvant treatment. We compared survival outcomes and patterns of recurrence of 53 patients treated by CTRT and those of 27 patients treated by CT.ResultsAfter a median follow-up of 38.48 months, CTRT resulted in a significant improvement of the 5-year PFS (60.9% vs. 36%, p = 0.03) and the 5-year OS (55.9% vs. 33%, p = 0.015) compared to adjuvant CT. The 5-year OS was significantly increased by adjuvant CTRT (p = 0.046) in patients with lymph node metastasis, and particularly those with advanced pN stage (p = 0.0078) and high lymph node ratio (LNR) exceeding 25% (p = 0.012). Also, there was a significant improvement of the PFS of patients classified pN2–N3 (p = 0.022) with a high LNR (p = 0.018). CTRT was also associated with improved OS and PFS in patients with lymphovascular and perineural invasion (LVI and PNI) compared to chemotherapy.ConclusionThere is a particular survival benefit of adding radiotherapy to chemotherapy in patients with selected criteria such as lymph node involvement, high LNR LVI, and PNI.     

Effects of Topical Bimatoprost 0.01% and Timolol 0.5% on Circadian IOP,Blood Pressure and Perfusion Pressure in Patients with Glaucoma or Ocular Hypertension: A Randomized,Double Masked,Placebo-Controlled Clinical Trial

PurposeTo compare the 24-hour (24h) effects on intraocular pressure (IOP) and cardiovascular parameters of timolol 0.5% and bimatoprost 0.01% in open angle glaucoma and ocular hypertensive subjects.MethodsIn this prospective, randomized, double masked, crossover, clinical trial, after washout from previous medications enrolled subjects underwent 24h IOP, blood pressure (BP) and heart rate (HR) measurements and were randomized to either topical bimatoprost 0.01% at night plus placebo in the morning or to timolol 0.5% bid. After 8 weeks of treatment a second 24h assessment of IOP, BP and HR was performed and then subjects switched to the opposite treatment for additional 8 weeks when a third 24h assessment was performed. The primary endpoint was the comparison of the mean 24h IOP after each treatment. Secondary endpoints included the comparisons of IOP at each timepoint of the 24h curve and the comparison of BP, HR, ocular perfusion pressure and tolerability.ResultsMean untreated 24h IOP was 20.3 mmHg (95%CI 19.0 to 21.6). Mean 24h IOP was significantly lower after 8 weeks of treatment with bimatoprost 0.01% than after 8 weeks of treatment with timolol 0.5% bid (15.7 vs 16.8 mmHg, p = 0.0003). Mean IOP during the day hours was significantly reduced from baseline by both drugs while mean IOP during the night hours was reduced by -2.3 mmHg (p = 0.0002) by bimatoprost 0.01% plus placebo and by -1.1 mmHg by timolol 0.5% bid (p = 0.06). Timolol 0.5% significantly reduced the mean 24h systolic BP from baseline, the diastolic BP during the day hours, the HR during the night hours, and the mean 24h systolic ocular perfusion pressure.ConclusionBoth Bimatoprost 0.01% and Timolol 0.5% are effective in reducing the mean 24h IOP from an untreated baseline but Bimatoprost 0.01% is more effective than timolol 0.5% throughout the 24h. Timolol 0.5% effect on IOP is reduced during the night hours and is associated with reduced BP, HR and ocular perfusion pressure.

Trial Registration

EU Clinical Trial Register and EudraCT# 2010-024272-26     

Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis

BackgroundDespite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients.MethodsAll RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043).ResultsFive studies met the eligibility criteria ofthe systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI −0.24, −0.14]; p = 0.01, I² = 86%), fasting blood glucose (MD: −0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I² = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I² = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: −0.99, [95% CI −1.25 to -0.73]; p < 0.00001, I² = 0%) and homeostasis model assessment of β-cell function (HOMA-β) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I² = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (α and β), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation.ConclusionTCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.     

Population-Based Study of Hypoglycemia in Patients with Type 1 Diabetes Mellitus Requiring Emergency Medical Services

ObjectiveTo report the population burden of hypo glycemia necessitating emergency medical services (EMS) and the long-term outcomes in patients with type 1 diabetes mellitus (T1DM) receiving different insulin treatments.MethodsWe retrieved all EMS calls because of hypoglycemia in patients with T1DM in Olmsted County, Minnesota, between January 1, 2003, and December 31, 2009, and reviewed the related medical records.ResultsDuring the 7-year study period, 531 EMS calls were made involving 208 patients with T1DM (112 men, 96 women; mean age 47 ± 13 years). Of the 208 patients, 137 (66%) were receiving multiple daily insulin (MDI) injections, 50 (24%) were receiving continuous sub cutaneous insulin infusion, 15 (7%) were receiving simple insulin (SI), 4 (2%) were treated with metformin + MDI, and 2 (1%) were not receiving treatment for diabetes (after pancreas transplantation). The last 2 groups were excluded from further analysis because of small sample size. The remaining 3 treatment groups differed by age (P < .02), with the oldest patients receiving SI. Repeated calls, emergency department transportation (EDT), and hospitalization had a 33%, 49%, and 18% frequency, respectively, and did not differ among the treatment groups. In a multivariate model, mortality was significantly associated with treatment type (the SI group had a higher risk for mortality than did the MDI group [P = .03] after exclusion of 27 patients who changed treatment during follow-up), age (P < .0001), and EDT (P = .04).ConclusionThe population burden of EMS-requiring hypoglycemia in patients with T1DM is high. Medical resource utilization was similar among the 3 treatment groups. Mortality was higher in the SI group (limited by small sample size) and among patients requiring EDT and increased with advancing age. Further research could be directed toward understanding the effect of expert evaluation of high-risk patients on long-term outcomes. (EndocrPract. 2012;18:834-841)