Looking into the Eyes to See the Heart of Chronic Kidney Disease Patients.

In patients with chronic kidney disease (CKD), the main cause of morbidity and mortality is cardiovascular disease (CVD). Both coronary artery calcium scoring by computed tomography (CT) and optical coherence tomography (OCT) are used to identify patients at increased risk for ischemic heart disease, thereby indicating a higher cardiovascular risk profile. Our study aimed to investigate the utility of these techniques in the CKD population. In patients with CKD, OCT was used to measure the choroidal thickness (CHT) and the thickness of the peripapillary retinal nerve fiber layer (pRNFL). A total of 127 patients were included, including 70 men (55%) with an estimated glomerular filtration rate (eGFR) of 39 ± 30 mL/min/1.73 m2. Lower pRNFL thickness was found to be related to high-sensitivity troponin I (r = -0.362, p < 0.001) and total coronary calcification (r = -0.194, p = 0.032). In a multivariate analysis, pRNFL measurements remained associated with age (ß = -0.189; -0.739--0.027; p = 0.035) and high-sensitivity troponin I (ß = -0.301; -0.259--0.071; p < 0.001). Severe coronary calcification (Agatston score ≥ 400 HU) was related to a worse eGFR (p = 0.008), a higher grade of CKD (p = 0.036), and a thinner pRNFL (p = 0.011). The ROC curve confirmed that the pRNFL measurement could determine the patients with an Agatston score of ≥400 HU (AUC 0.638; 95% CI 0.525-0.750; p = 0.015). Our study concludes that measurement of pRNFL thickness using OCT is related to the markers associated with ischemic heart disease, such as coronary calcification and high-sensitivity troponin I, in the CKD population.

Influence of Physiological Variables and Comorbidities on Plasma Aß40, Aß42, and p-tau181 Levels in Cognitively Unimpaired Individuals.

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aß40, Aß42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aß40 and Aß42 levels but not on the Aß42/Aß40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aß40 and Aß42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.

Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

BACKGROUND: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. OBJECTIVES: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. MATERIALS AND METHODS: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. RESULTS: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 µg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). DISCUSSION AND CONCLUSION: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Accuracy of plasma Aß40, Aß42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform.

BACKGROUND: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aß40, Aß42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. METHODS: Both plasma and CSF Aß40, Aß42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors. RESULTS: Aß42, amyloid ratio, p-tau181, and p-tau181/Aß42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89. CONCLUSIONS: Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer's pathology in cognitively unimpaired subjects.

Low levels of proinflammatory cytokines in a transdiagnostic sample of young male and female early onset eating disorders without any previous treatment: A case control study.

Growing interest exists in the association of the immune system and its role in the development and maintenance of eating disorders (ED). Current evidence suggests that serum cytokine levels seem to be elevated in females with anorexia nervosa (AN). However, less is known in bulimia nervosa (BN) and other specified feeding and eating disorders (OSFED), specially in males. We aimed to perform a case-control study in a sample of forty eight young patients (38 females and 10 males) with early diagnosis of AN, BN or OSFED and without any previous treatment, compared with twenty nine healthy controls (19 females and 10 males) matched by age, sex and socioeconomic status. We evaluated eating-related psychopathology and depressive symptoms and measured serum concentration of proinflammatory cytokines IL-1ß, IL-6, and TNF-α and anti-inflammatory cytokine IL-10. Contrary to expectations, levels of IL-1ß and IL-6 were significantly lower in ED patients, compared with healthy controls. Comparing the different groups of females, we found elevated levels of IL-10 among ED patients therefore supporting the idea of an immunosuppressive status in the early stages. This could indicate that early onset patients without any previous treatment could remain in a reward-dependent state with a lower immune response.

Growth Differentiation Factor 15 Is Superior to Troponin I in the Evaluation of Kidney Transplant Candidates.

INTRODUCTION: Pretransplant cardiac troponin I (cTNI) has demonstrated its predicting value in survival after kidney transplant. Growth differentiation factor 15 (GDF-15) is a biomarker currently studied as a predictor of mortality and cardiovascular events (CVE) in different scenarios. The aim of this study was to compare the utility of these two biomarkers in the prediction of events after kidney transplant. METHODS: We included 359 kidney transplants performed in our center between 2005 and 2015. cTNI and GDF-15 were measured on stored serum samples obtained pretransplant. RESULTS: Median GDF-15 was 5,346.4 pg/mL, and cTNI was 5.6 ng/L. After follow-up, 77 (21.5%) patients died, and the incidence of cerebrovascular accident (CVA), acute coronary syndrome (ACS), and major adverse CVEs (MACE) was 6.38%, 12.68%, and 20.56%, respectively. Patients were stratified in tertiles according to GDF-15 and cTNT levels. By multivariate cox regression analysis including both biomarkers and different clinical characteristics, we found a significant relation between GDF-15 and mortality, CVAs, and MACE (highest tertile hazard ratio [HR] 2.2 95% confidence interval [CI] [1.2-4.1], p = 0.01, HR 9.7 CI 95% [2.2-43.1], p = 0.003 and HR 2.7 CI 95% [1.4-5.1], p = 0.002). On the contrary, posttransplant ACS was related to cTNI (highest cTNI tertile HR 3.2 CI 95% [1.5-7.3], p = 0.003). DISCUSSION: Our study indicates the potential utility of GDF-15 as a mortality and CVE predictor after kidney transplant and its superiority compared to cTNI. By contrast, probably due to its tissue specificity, cardiac troponin showed a stronger correlation with acute coronary events. Although more studies are needed to confirm our findings, these two molecules could be used in conjunction with other tools to predict adverse events after transplant and ideally find strategies to minimize them.

Urinary CXCL10 specifically relates to HLA-DQ eplet mismatch load in kidney transplant recipients.

BACKGROUND: Urinary CXCL10 (uCXCL10) is associated with graft inflammation and graft survival, but the factors related to its excretion are not well known. HLA molecular matching at epitope level allow estimating the "dissimilarity" between donor and recipient HLA more precisely, being better related to further transplant outcomes. The relationship between uCXCL10 and HLA molecular mismatch has not been previously explored. METHODS: HLA class I and class II typing of some 65 recipients and their donors was retrospectively performed by high resolution sequence-specific-primer (Life Technologies, Brown Deer, WI). The HLA-Matchmaker 3.1 software was used to assess eplet matching. Urine samples collected on the day of the 1-year surveillance biopsy were available of these 65 patients. uCXCL10 was measured using a commercial enzyme-linked immunoassay kit. RESULTS: 1-year uCXCL10 was independently associated with HLA-DQB1 eplet mismatch load (ß 0.300, 95%CI 0.010-0.058, p = 0.006). Kidney transplant recipients with a HLA-DQB1 eplet mismatch load >3 showed higher values of uCXCL10 at 1-year (p = 0.018) than those with ≤3. Patients with a HLA-DQB1 eplet mismatch load >3 with subclinical AbMR had significantly higher levels of the logarithm of 1-year uCXCL10 (No AbMR 0.88, IQR 0.37; AbMR 1.38, IQR 0.34, p = 0.002) than those without AbMR. CONCLUSIONS: uCXCL10 specifically relates to HLA-DQ eplet mismatch load. This relationship can partly explain the previously reported association between uCXCL10 excretion and graft inflammation. An adequate evaluation of any potential non-invasive biomarker, such as uCXCL10, must take into account the HLA molecular mismatch.

Mild Hypophosphatemia-Associated Conditions in Children: The Need for a Comprehensive Approach.

To better understand the causes of hypophosphatemia in children, we evaluated all serum phosphate tests performed in a tertiary hospital with unexpected but persistent temporary or isolated hypophosphatemia over an 18 year period. We collected 29,279 phosphate tests from 21,398 patients, of which 268 (1.2%) had at least one result showing hypophosphatemia. We found that endocrinopathies (n = 60), tumors (n = 10), and vitamin D deficiency (n = 3) were the medical conditions most commonly associated with mild hypophosphatemia, but in many patients the cause was unclear. Among patients with endocrinopathies, those with diabetes mellitus were found to have lower mean serum phosphate levels (mean 3.4 mg/dL) than those with short stature (3.7 mg/dL) or thyroid disorders (3.7 mg/dL). In addition, we found a correlation between glycemia and phosphatemia in patients with diabetes. However, despite the potential relevance of monitoring phosphate homeostasis and the underlying etiologic mechanisms, renal phosphate losses were estimated in less than 5% of patients with hypophosphatemia. In the pediatric age group, malignancies, hypovitaminosis D, and endocrine disorders, mostly diabetes, were the most common causes of hypophosphatemia. This real-world study also shows that hypophosphatemia is frequently neglected and inadequately evaluated by pediatricians, which emphasizes the need for more education and awareness about this condition to prevent its potentially deleterious consequences.

Hyperbaric Oxygen Therapy Does Not Have a Negative Impact on Bone Signaling Pathways in Humans.

INTRODUCTION: Oxygen is emerging as an important factor in the local regulation of bone remodeling. Some preclinical data suggest that hyperoxia may have deleterious effects on bone cells. However, its clinical relevance is unclear. Hence, we studied the effect of hyperbaric oxygen therapy (HBOT) on serum biomarkers reflecting the status of the Wnt and receptor activator of NF-κB ligand (RANKL) pathways, two core pathways for bone homeostasis. MATERIALS AND METHODS: This was a prospective study of 20 patients undergoing HBOT (mean age 58 yrs., range 35-82 yrs.) because of complications of radiotherapy or chronic anal fissure. Patients were subjected to HBOT (100% oxygen; 2.4 atmospheres absolute for 90 min). The average number of HBOT sessions was 20 ± 5 (range 8-31). Serum hypoxia-inducible factor 1-α (HIF1-α), osteoprotegerin (OPG), RANKL, and the Wnt inhibitors sclerostin and dickkopf-1 (DKK1) were measured at baseline and after HBOT by using specific immunoassays. RESULTS: HIF-1α in eight patients with measurable serum levels increased from 0.084 (0.098) ng/mL at baseline to 0.146 (0.130) ng/mL after HBOT (p = 0.028). However, HBOT did not induce any significant changes in the serum levels of OPG, RANKL, sclerostin or DKK1. This was independent of the patients' diagnosis, either neoplasia or benign. CONCLUSION: Despite the potential concerns about hyperoxia, we found no evidence that HBOT has any detrimental effect on bone homeostasis.

Bexarotene Impairs Cognition and Produces Hypothyroidism in a Mouse Model of Down Syndrome and Alzheimer's Disease.

All individuals with Down syndrome (DS) eventually develop Alzheimer's disease (AD) neuropathology, including neurodegeneration, increases in ß-amyloid (Aß) expression, and aggregation and neurofibrillary tangles, between the third and fourth decade of their lives. There is currently no effective treatment to prevent AD neuropathology and the associated cognitive degeneration in DS patients. Due to evidence that the accumulation of Aß aggregates in the brain produces the neurodegenerative cascade characteristic of AD, many strategies which promote the clearance of Aß peptides have been assessed as potential therapeutics for this disease. Bexarotene, a member of a subclass of retinoids that selectively activates retinoid receptors, modulates several pathways essential for cognitive performance and Aß clearance. Consequently, bexarotene might be a good candidate to treat AD-associated neuropathology. However, the effects of bexarotene treatment in AD remain controversial. In the present study, we aimed to elucidate whether chronic bexarotene treatment administered to the most commonly used murine model of DS, the Ts65Dn (TS) mouse could reduce Aß expression in their brains and improve their cognitive abilities. Chronic administration of bexarotene to aged TS mice and their CO littermates for 9 weeks diminished the reference, working, and spatial learning and memory of TS mice, and the spatial memory of CO mice in the Morris water maze. This treatment also produced marked hypoactivity in the plus maze, open field, and hole board tests in TS mice, and in the open field and hole board tests in CO mice. Administration of bexarotene reduced the expression of Aß1-40, but not of Aß1-42, in the hippocampi of TS mice. Finally, bexarotene increased Thyroid-stimulating hormone levels in TS mice and reduced Thyroid-stimulating hormone levels in CO mice, while animals of both karyotypes displayed reduced thyroxine levels after bexarotene administration. The bexarotene-induced hypothyroidism could be responsible for the hypoactivity of TS and CO mice and their diminished performance in the Morris water maze. Together, these results do not provide support for the use of bexarotene as a potential treatment of AD neuropathology in the DS population.

Urinary C-X-C Motif Chemokine 10 Is Related to Acute Graft Lesions Secondary to T Cell- and Antibody-Mediated Damage.

BACKGROUND Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-g-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. MATERIAL AND METHODS A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. RESULTS Banff scores 't', 'i', 'g', and 'ptc' were significantly related to urinary CXCL10 levels. Multivariate analysis showed that 't' (ß=0.107, P=0.001) and 'ptc' (ß=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799-11.646, P=0.001) after multivariate regression analysis. CONCLUSIONS DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.

Growth Differentiation Factor 15: A Biomarker with High Clinical Potential in the Evaluation of Kidney Transplant Candidates.

Kidney transplantation implies a significant improvement in patient survival. Nevertheless, early mortality after transplant remains high. Growth differentiation factor 15 (GDF-15) is a novel biomarker under study as a mortality predictor in multiple scenarios. The aim of this study is to assess the utility of GDF-15 to predict survival in kidney transplant candidates. For this purpose, 395 kidney transplant recipients with pretransplant stored serum samples were included. The median GDF-15 was 5331.3 (50.49-16242.3) pg/mL. After a mean of 90.6 ± 41.5 months of follow-up, 82 (20.8%) patients died. Patients with higher GDF-15 levels (high risk tertile) had a doubled risk of mortality after adjustment by clinical characteristics (p = 0.009). After adjustment by EPTS (Estimated Post Transplant Survival score) the association remained significant for medium hazards ratios (HR) 3.24 95%CI (1.2-8.8), p = 0.021 and high risk tertiles HR 4.3 95%CI (1.65-11.54), p = 0.003. GDF-15 improved the prognostic accuracy of EPTS at 1-year (ΔAUC = 0.09, p = 0.039) and 3-year mortality (ΔAUC = 0.11, p = 0.036). Our study suggests an independent association between higher GDF-15 levels and mortality after kidney transplant, adding accuracy to the EPTS score, an established risk prediction model currently used in kidney transplant candidates.

[Prevalence and risk factors associated with diabetic retinopathy in Santander. Northern Spain]. / Prevalencia y factores de riesgo asociados a la retinopatía diabética en Santander. Norte de España.

OBJETIVE: To assess the prevalence and risk factors associated with diabetic retinopathy (DR) in Cantabria. DESIGN: ross-sectional population based study. LOCATION: Health center of Cantabria. PARTICIANTS: A random sample of 442 patients with type 2 diabetes. MAIN MEASUREMENTS: Non-mydiatric retinography, classifying them according to the International Clinical Diabetic Retinopathy Disease Severity Scale. The analyzed risk factors were: age, gender, age at diabetes onset, duration of diabetes, glycated haemoglobin levels (A1C), treatment of diabetes, blood pressure (systolic and diastolic), serum lipids concentration, body mass index, smoking status, hematocrit, pregnancy, serum vitamin D (25 OH D) levels, nephropathy and cardiovascular events. RESULTS: The prevalence of DR was 8.56% (CI: 5.81-11.32): Mild non-proliferative DR: 5.07% (CI: 2.89-7.25); Moderate non-proliferative DR: 1.38% (CI: 0.17-2.60); Severe non-proliferative DR: 0.27% (CI: 0.006-1.28); proliferative DR: 1.84% (CI: 0.46-3.22). Diabetic macular oedema: 2.30% (CI: 0.77-3.83). Mean age: 70 years, mean diagnostic age: 58.97 years, mean body mass index 29.86, 78.40% patients with hypertension, 67.30% dyslipidemia and median A1C: 6.7%. A deficit of 25 (OH) D was identified in 77% of patients. In the multivariate analysis, treatment of type 2 diabetes, body mass index, duration of diabetes and metabolic control of glycaemia were identified as independent risk factors. CONCLUSIONS: The prevalence of DR, compared with former studies, has decreased to 8.56%; this decrease is associated with the improvement in the control of modifiable risk factors. The associated independent risk factors were: treatment, body mass index, duration and control of diabetes. The variables antihypertensive treatment, cardiovascular events and nephropathy showed predictive value for DR.

Bone mineral density evolution and incidence of fractures in a cohort of patients with primary hyperparathyroidism treated with parathyroid surgery vs active surveillance during 6 years of follow-up. / Evolución de la densidad mineral ósea y aparición de fracturas en una cohorte de pacientes con hiperparatiroidismo primario tratados con cirugía paratiroidea vs. vigilancia activa sin cirugía en 6 años de seguimiento.

INTRODUCTION: The need for parathyroidectomy to treat asymptomatic patients with primary hyperparathyroidism is controversial. The aim of this study was to assess the impact of parathyroidectomy vs. surveillance on skeletal outcomes such as bone mineral density (BMD) and incident fractures. METHODS: This was a retrospective cohort study including 170 patients (112 treated with surgery and 58 subject to active surveillance) between 1991 and 2014. Changes in BMD in lumbar spine, femoral neck, total hip, and radius, and incidence of fractures, were monitored for 2-6 years. RESULTS: Patients treated with surgery had BMD gains at 2years of 4.37%, as compared to 1.59% in non-operated patients (p<0.05) in the lumbar spine, 3.90% vs. 0.19% (p<0.05) in the femoral neck, and 2.70% vs. 0.14% (p<0.05) in total hip. Gain in BMD in the lumbar spine and femoral neck remained significant in operated patients at 4 and 6 years. No improvement was seen in the radius in operated patients. No significant difference was seen in fracture occurrence between operated and non-operated patients. CONCLUSION: Patients with primary hyperparathyroidism treated with surgery experience greater BMD gains than non-operated patients, especially in the lumbar spine and femoral neck. The risk of fracture does not decrease in the group of operated patients.

The Ratio Serum Creatinine/Serum Cystatin C (a Surrogate Marker of Muscle Mass) as a Predictor of Hospitalization in Chronic Obstructive Pulmonary Disease Outpatients.

BACKGROUND: In chronic obstructive pulmonary disease (COPD), low muscle mass has been associated with several clinical outcomes such as low exercise capacity, hospital admission, and mortality. The Sarcopenia Index (SI) is a novel way to estimate muscle mass based on the ratio of serum creatinine (produced exclusively by muscle)/cystatin C (produced by all nucleated body cells). OBJECTIVES: This study aims to assess the SI in stable COPD outpatients, as compared with a healthy control group, to quantify its relationship with several important clinical features in COPD, and to study its potential usefulness to predict COPD exacerbations and hospital admissions. METHODS: The SI was calculated in 18 healthy control subjects and 65 stable COPD outpatients were included in the study. Patients were prospectively followed for 1 year after being enrolled in the study. RESULTS: COPD patients had a lower SI than controls, that is lower muscle mass. Furthermore, patients with a modified Medical Research Council dyspnea score ≥2, patients with a COPD Assessment Test score ≥10, and patients with a high risk of exacerbation had lower levels of SI compared with patients without these characteristics. SI correlated with FEV1 (r = 0.491, p < 0.001), the 6-min walking test (r = 0.560, p = 0.001), and the Fat-Free Mass Index (r = 0.431, p = 0.017). Univariate and multivariate Cox proportional risk analysis showed that a low SI is an independent predictor of hospital admission in COPD outpatients followed for 1 year (HR 5.16, p = 0.025). CONCLUSIONS: The ratio serum creatinine/serum cystatin C correlates with several COPD characteristics, and it can be used to predict COPD hospitalization.

Analysis of the influence of the T393C polymorphism of the GNAS gene on the clinical expression of primary hyperparathyroidism.

BACKGROUND: The receptor of parathyroid hormone and parathyroid hormone-related-protein (PTH/PTHrp) is located in the cell membrane of target tissues - kidney and osteoblasts. It is a G protein-coupled-receptor whose Gsα subunit is encoded by the GNAS gene. Our aim was to study whether the single nucleotide polymorphism (SNP) T393C of the GNAS gene is associated with renal stones, bone mineral density (BMD), or bone remodelling markers in primary hyperparathyroidism (PHPT). METHODS: An analysis was made of clinical and biochemical parameters and densitometric values in three areas and their relationship with the T393C SNP of the GNAS gene in 261 patients with primary hyperparathyroidism and in 328 healthy controls. Genotyping was performed using the Custom Taqman® SNP Genotyping assay. RESULTS: The genotype frequencies of GNAS T/C 393 were similar in the control and PHPT groups. No association was found between genotypes and clinical expression of PHPT (renal stones and bone fractures). A nonstatistically significant trend was seen to lower BMD in the lumbar spine, femoral neck, and total hip in both PHPT and control C homozygote subjects. CONCLUSION: Genetic susceptibility to PHPT related to the GNAS T393C polymorphism or a major influence in its development and clinical expression were found. A C allele-related susceptibility to lower BMD in trabecular bone in both PHPT and control subjects is not sufficient to suggest a more severe clinical expression of PHPT. This trend may be considered as a basis for further studies with larger sample sizes and complementary functional evaluation.

Impacto del empleo de umbrales específicos de referencia en el diagnóstico de las alteraciones funcionales tiroideas en la mujer gestante / Impact of using specific reference intervals on the diagnosis of thyroid dysfunction during pregnancy

Objetivo: Establecer los umbrales específicos de referencia de cada uno de los parámetros de función tiroidea en cada trimestre de la gestación y determinar el impacto del uso de umbrales no específicos en el diagnóstico de las alteraciones funcionales en el primer trimestre. Métodos: Entre enero y septiembre de 2014 se contactaron 759 mujeres embarazadas con edad mayor de 18 años y sin alteraciones funcionales tiroideas conocidas. Tras excluir a todas las pacientes que no completaron el seguimiento durante toda la gestación y las que presentaron inmunidad tiroidea positiva, 411 gestantes configuraron nuestra población de referencia. Se determinaron los niveles de TSH, T4L y T3L en cada trimestre, los anticuerpos antiperoxidasa tiroidea y antitiroglobulina en el primero y se recogió una muestra de orina en los trimestres primero y tercero para la determinación del yodo urinario. Resultados: Un total de 411 gestantes completaron el seguimiento en los 3 trimestres. Un 38,69% consumían sal yodada y un 72,20% suplementos yodados. Los valores de referencia de TSH expresados como mediana y percentiles 2,5 y 97,5 fueron: 1,53 μUI/ml (0,26-3,95), 1,90 μUI/ml (0,78-3,85) y 1,89 μUI/ml (0,71-3,61) en el primer, segundo y tercer trimestre, respectivamente. El nivel de yoduria fue de 171,31 μg/l (90,7-274,9) en el primer trimestre y de 190,37 μg/l (96,44-360,38) en el tercero. La aplicación en el primer trimestre de los umbrales propuestos por las sociedades internacionales ocasionaría una clasificación errónea del 19,8% de las gestantes en relación con su función tiroidea, mientras que los umbrales no específicos de nuestro laboratorio lo harían en el 8,52%. Conclusiones: La utilización de umbrales no específicos para el diagnóstico de las alteraciones funcionales tiroideas durante la gestación ocasiona un importante porcentaje de errores de clasificación, contribuyendo a una atención inadecuada.

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Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitamin D.

Traditionally, calcitriol has been considered a calcium and phosphate regulating hormone, but has recently been shown to play a pivotal role in innate immunity. Many barrier and immune cells have membrane and intracellular receptors that recognize different microbial antigens. Activation of these receptors induces synthesis of 1α-hydroxylase, which acts on 25 hydroxyvitamin D to generate intracellular calcitriol. Calcitriol activates its receptor and enhances the synthesis of important human antibiotics like cathelicidin and ß2-defensin while inhibiting hepcidin. These pluripotent peptides have an important role in innate immunity, and their regulation is abnormal in hypovitaminosis D. The literature on their secretion mechanisms, levels in different organic fluids, mechanism of action, and relationship with vitamin D is reviewed here.

Rs219780 SNP of Claudin 14 Gene is not Related to Clinical Expression in Primary Hyperparathyroidism.

BACKGROUND: The CLDN14 gene encodes a protein involved in the regulation of paracellular permeability or ion transport at epithelial tight junctions as in the nephron. The C allele of the rs219780 SNP (single nucleotide polymorphism) of CLDN14 has been associated with renal lithiasis, high levels of parathormone (PTH), and with low bone mineral density (BMD) in healthy women. Our aim is to study the relationship between rs219780 SNP of CLDN14 and renal lithiasis, fractures, and BMD in patients with primary hyperparathyroidism (PHPT). METHODS: We enrolled 298 Caucasian patients with PHPT and 328 healthy volunteers in a cross-sectional study. We analysed anthropometric data, history of fractures or kidney stones, biochemical parameters including markers for bone remodelling, abdominal ultrasound, and BMD and genotyping for the rs219780 SNP of CLDN14. RESULTS: We did not find any difference in the frequency of fractures or renal lithiasis between the genotype groups in PHPT patients. Moreover, we did not find any relationship between the T or C alleles and BMD or biochemical parameters. CONCLUSIONS: rs219780 SNP of CLDN14 does not appear to be a risk factor for the development of PHPT nor does it seem to influence the clinical expression of PHPT.