Adherence to Dietary Patterns and Cardiovascular Disease Risk: A Cross-Sectional Study of Total Carotid Plaque Area in Argentina.

Objective: Assessing subclinical atherosclerosis (sAT) is crucial for preventing cardiovascular disease. The Mediterranean diet is considered the gold standard for cardiovascular protection, but cultural and economic barriers can hinder adherence to it. The prudent dietary pattern (DP) has been associated with protective effects against chronic diseases. However, its impact on primary cardiovascular prevention remains uncertain. This study examined adherence to various DPs and their effect on sAT, measured by total carotid plaque area (TPA). Methods: This cross-sectional study included 116 adults enrolled in a cardiovascular prevention program. Demographic, clinical, laboratory, and TPA data were collected. Adherence to DPs was assessed using a food frequency questionnaire. Participants were categorized according to their adherence to 4 mutually exclusive DPs: prudent, traditional, sweet, and mixed. Generalized linear models were used to assess the effect of DPs on TPA, adjusting for relevant cardiovascular variables. Results: The traditional, sweet, and mixed DPs were associated with higher TPA values than the prudent DP, with medians (interquartile range) of 27 (99), 39 (49), 27.5 (58), and 0 (36) mm2, respectively. Gamma regression analysis found that the beta exponents for the traditional, sweet, and mixed DPs versus the prudent DP were 3.78 (p=0.046); 3.73 (p=0.013), and 2.20 (p=0.072), respectively. Systolic blood pressure values were higher for the sweet and mixed DPs than for the prudent DP (133.9±11.7; 132.5±13.9 and 122.7±8.8 mmHg, respectively; p<0.05). Conclusion: These findings underscore the importance of additional research and targeted interventions to promote healthier DPs to promote improvements in cardiovascular health.

Kidney stone matrix proteins: Role in stone formation.

Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.

Nuevas estrategias terapéuticas para tratar la hiperfosfatemia en la IRC: foco en la absorción intestinal / New therapeutic strategies to treat hyperphosphatemia in CRF: focus on intestinal absorption

RESUMEN El manejo de la hiperfosfatemia de los pacientes con insuficiencia renal crónica en diálisis permanece como un desafío. A pesar de utilizar un enfoque multifacético que incluye la restricción dietética, la remoción de fósforo por la diálisis y el uso de quelantes de fósforo, esta estrategia múltiple no logra reducir los niveles de fósforo en más de 2 mg/dl. El control de fósforo de los pacientes en diálisis es fundamental en razón de la relación monotónica entre los niveles séricos de fosfato y el incremento del riesgo cardiovascular. Por lo tanto, hay una necesidad de explorar nuevas estrategias para reducir los niveles séricos de fosfato a niveles normales. Recientes avances en nuestra compresión de los mecanismos que subyacen a la homeostasis del fósforo sugieren que el transporte gastrointestinal del fósforo podría ser un objetivo. Recientemente se han desarrollado inhibidores de los cotransportadores sodio fosfato del intestino y se ha revalorizado el uso de la nicotinamida, en su formulación de liberación prolongada, que también actuaria por ese mecanismo. También se han drogas como el tenapanor, que inhibiendo el intercambiador sodio/hidrogeno isoforma 3 del enterocito, disminuyen la absorción paracelular de fósforo.

ABSTRACT Management of hyperphosphatemia in patients with chronic renal failure on dialysis remains challenging. Despite using a multifaceted approach that includes dietary restriction, phosphorus removal by dialysis, and phosphate binders, these multiple strategies fail to reduce phosphorus levels by more than 2 mg/dL. Phosphorus control in dialysis patients is essential due to the monotonic relationship between serum phosphate levels and increased cardiovascular risk. Therefore, there is a need to explore new strategies to reduce serum phosphate levels to normal levels. Recent advances in understanding the mechanisms underlying phosphorus homeostasis suggest that the gastrointestinal transport of phosphorus could be a target. Inhibitors of intestinal sodium phosphate cotransporters recently developed, and using of nicotinamide, in its prolonged release formulation, which would also act by this mechanism, has been revalued. There have also been drugs such as tenapanor, which, by inhibiting the isoform three sodium/hydrogen exchanger of the enterocyte, decreases the paracellular absorption of phosphorus.

Role of prolyl hydroxylase/HIF-1 signaling in vascular calcification.

Morbidity and mortality of chronic kidney disease (CKD) patients are largely associated with vascular calcification, an actively regulated process in which vascular smooth muscle cells (VSMCs) change into cells similar to osteocytes/chondrocytes, known as trans-differentiation. Cellular and systemic response to low oxygen (hypoxia) is regulated by the prolyl hydroxylase/hypoxia-inducible factor (HIF)-1 pathway. Recent studies highlighted that hypoxia-mediated activation of HIF-1 induces trans-differentiation of VSMCs into bone-forming type through an increase in osteo-/chondrogenic genes. Inhibition of the HIF-1 pathway abolished osteochondrogenic differentiation of VSMCs. Hypoxia strongly enhanced elevated phosphate-induced VSMC osteogenic trans-differentiation and calcification. HIF-1 was shown to be essential for phosphate enhanced VSMC calcification. O2-dependent degradation HIF-1 is triggered by the prolyl hydroxylase domain proteins (PHD). Prolyl hydroxylase inhibitors, daprodustat and roxadustat, increase high phosphate-induced VC in VSMCs, stabilizing HIF-1α and activating the HIF-1 pathway in these cells. Whether the use of these PHD inhibitors to treat anemia in CKD patients will favor the development and progression of vascular calcification remains to be explored.

Echocardiogram in Critically ill Patients with COVID-19: ECOVID Study

Abstract Background Literature is scarce on echocardiographic characteristics of COVID-19 patients admitted to the intensive care unit (ICU). Objectives To describe echocardiographic characteristics of ICU COVID-19 patients and associate them with clinical signals/symptoms, laboratory findings and outcomes. Methods Patients with RT-PCR-confirmed COVID-19, admitted to the ICU, who underwent echocardiography were included. Clinical characteristics associated with an abnormal echocardiogram (systolic ventricular dysfunction of any degree — left and/or right ventricle — and/or high filling pressures and/or moderate to severe pericardial effusion) were analyzed. Groups were compared using the Student's t-test, chi-square, and logistic regression. A p < 0.05 was considered statistically significant. Results A total of 140 patients met inclusion criteria, and 74 (52.9%) had an abnormal echocardiogram. A low number of left and right ventricular systolic dysfunction was observed, and 35% of the population had a normal diastolic function. In the univariate analysis, characteristics associated with abnormal echocardiogram were age, chronic kidney disease, elevated troponin, previous heart failure, and simplified acute physiology score 3 (SAPS 3). In the regression model, troponin and SAPS3 score were independent markers of abnormal echocardiogram. An abnormal echocardiogram was associated with a higher prevalence of in-hospital death (RR 2.10; 95% CI 1.04-4.24) and orotracheal intubation (RR 2.3; 95% CI 1.14-4.78). Conclusions COVID-19 has little effect on ventricular function, but it is common to find increased filling pressures. Elevated serum troponin level and SAPS3 score were the independent markers of an abnormal echocardiogram. In addition, the prevalence of in-hospital death and need for mechanical ventilation were higher in patients with abnormal echocardiogram.

New Complex of Cryptic Species Discovered in Genus Biblis (Papilionoidea: Nymphalidae: Biblidinae) in Mexico.

Our research focuses on demonstrating the existence of cryptic species named under Biblis aganisa Boisduval. We used COI sequences to delimit Biblis species for Mexico using species delimitation analyses and examined phylogenetic relationships with sequences from Mexico, Costa Rica, Argentina, USA, and Guana Island using a Bayesian inference tree. We performed a discriminant analysis with quantitative traits using female and male wing and genitalia, and a tree of maximum parsimony based on 39 qualitative characters of wings, head, and male genitalia. The results were congruent in the three analyses. Three groups were formed based on DNA, ECO 01 + DHJ02, ECO 02 + DHJ01, and ECO 03. The characters that contributed over 50% separation were for wings: wing length, anal margin length, and distance from the band to the outer margin; for male genitalia, angle of the integument, uncus, and the length of the hypandrium, while for females, it was the angle of the anteapophysis and the length of the abdomen. For the analysis of qualitative characters, a tree of maximum parsimony was obtained where 20 characters were informative. We confirmed the existence of three cryptic Biblis species in Mexico, two not yet described, and one corresponding to B. aganisa (ECO 02), which is sympatric in Oaxaca and Sinaloa (ECO 03) and in the Yucatan Peninsula (ECO 01).

Role of claudins in idiopathic hypercalciuria and renal lithiasis.

Paracellular transport in the kidney is mediated by a family of proteins located in the tight junctions called claudins which confers its ionic selectivity. Claudin-2 is highly expressed in the proximal tubule and descending limb of Henle and mediate paracellular reabsorption of sodium and calcium cations. In the thick ascending limb of Henle (TALH) calcium is reabsorbed by a paracellular channel formed by Claudin-16 and-19. Claudin-16 mediates cationic permeability while Claudin-19 increases the cationic selectivity of Claudin-16 by blocking anionic permeability. On the other hand, Claudin 14, that is also located in TALH, inhibits the paracellular permeability of Claudin-16 to calcium. Recent wide genomic association analysis studies have detected four common synonymous variants (genetic polymorphisms of a single nucleotide, SNPs) at the locus of Claudin-14 gene that were significantly associated with the presence of renal lithiasis. Another study of wide genomic association and nephrolithiasis was carried out in the general population but including chromosome X, where claudin-2 gene is located. They detected nine SNPs that had a significant association with renal lithiasis risk. A greater knowledge of the paracellular pathway controlled by claudins and its regulation will allow us to develop future new treatments for idiopathic hypercalciuria and renal lithiasis.

Hyponatremia, Inflammation at Admission, and Mortality in Hospitalized COVID-19 Patients: A Prospective Cohort Study.

Background: Systemic inflammation has been associated with severe coronavirus disease 2019 (COVID-19) disease and mortality. Hyponatremia can result from inflammation due to non-osmotic stimuli for vasopressin production. Methods: We prospectively studied 799 patients hospitalized with COVID-19 between March 7 and November 7, 2020, at Hospital Posadas in Buenos Aires, Argentina in order to evaluate the association between hyponatremia, inflammation, and its impact on clinical outcomes. Admission biochemistries, high-sensitivity C-reactive protein (hsCRP), ferritin, patient demographics, and outcome data were recorded. Outcomes (within 30 days after symptoms) evaluated included ICU admission, mechanical ventilation, dialysis-requiring acute kidney injury (AKI), and in-hospital mortality. Length of hospital stay (in days) were evaluated using comprehensive data from the EHR. Results: Hyponatremia (median Na = 133 mmol/L) was present on admission in 366 (45.8%). Hyponatremic patients had higher hsCRP (median 10.3 [IR 4.8-18.4] mg/dl vs. 6.6 [IR 1.6-14.0] mg/dl, p < 0.01) and ferritin levels (median 649 [IQR 492-1,168] ng/dl vs. 393 [IQR 156-1,440] ng/dl, p = 0.02) than normonatremic patients. Hyponatremia was associated with higher odds of an abnormal hsCRP (unadjusted OR 5.03, 95%CI: 2.52-10.03), and remained significant after adjustment for potential confounders (adjusted OR 4.70 [95%CI: 2.33-9.49], p < 0.01). Hyponatremic patients had increased mortality on unadjusted (HR 3.05, 95%CI: 2.14-4.34) and adjusted (HR 2.76, 95%CI:1.88-4.06) in Cox proportional hazard models. Crude 30-day survival was lower for patients with hyponatremia at admission (mean [SD] survival 22.1 [0.70] days) compared with patients who were normonatremic (mean [SD] survival 27.2 [0.40] days, p < 0.01). Conclusion: Mild hyponatremia on admission is common, is associated with systemic inflammation and is an independent risk factor for hospital mortality. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04493268.

An intensive follow-up in subjects with cardiometabolic high-risk.

BACKGROUND AND AIM: Addressing chronic problems requires a model of care that promotes self-management of the disease and facilitates adherence to treatment. This project was designed to enhance patient's clinical and functional outcomes through a Comprehensive Model to be implemented in our health system and to evaluate the results. METHODS AND RESULTS: Different population stratification tools were tested and designed to classify subjects according to different variables. We have developed a program to detect and screen cardiometabolic risk by integrating most of the Chronic Care Model recommendations through in-house developed management software (MoviHealth®). From the results, 1317 subjects were evaluated (27% of the whole population) during the first year of follow-up which significantly improved for all variables along the follow-up period. The blood pressure of the hypertensive population in 2010 and 2015 showed the importance of enrollment of subjects and the optimization of the blood pressure control. The result of HbA1c observed in 2010 decreased progressively to 7.1 ± 1.4% in 2015, and dyslipidemia levels improved gradually. The number of cardiovascular events requiring hospitalization decreased significantly (48%), from 1.9 events per 100 subjects in 2011 to 0.98 in 2015. CONCLUSION: Our program has combined strategies for the prevention and control of non-communicable diseases, incorporating interventions to control risk factors and to reduce morbidity and mortality. It also had improvements in life quality, accessibility to health-care services, and the promotion of self-care.

Sarcopenia in hemodialysis patients from Buenos Aires, Argentina.

OBJECTIVES: Sarcopenia is the loss of skeletal muscle mass and function that occurs with aging that can lead to greater morbidity and mortality. Chronic kidney disease and hemodialysis (HD) favors the development of sarcopenia. We studied the prevalence of sarcopenia and its components using European Working Group on Sarcopenia in Elderly People 2 proposed criteria and risk factors for its development in HD patients. METHODS: In 100 adult HD patients, we evaluated: hand grip strength (HGS), muscle mass by dual energy X-ray absorptiometry and physical performance (gait-speed and sit-stand test). RESULTS: Sixty patients were male and 40 were female; mean age 55.6 years. Prevalence of sarcopenia was 16% (11.1% in males and 25% in females; P = 0.05); 7% had severe sarcopenia. Prevalence of low HGS was 33% in males and 28% in females; low muscle mass was 30% in males but 70% in females and low physical performance 23% in males and 45% in females. Falls were reported by 23 patients. Patients with lower HGS had a higher prevalence of falls in the last year (40% two or more falls; P = 0.03). Only females with sarcopenia had lower bone mineral content. Neither age, body mass index, time on dialysis, or prevalence of diabetes predicted sarcopenia. CONCLUSIONS: A significant proportion of dialysis patients had sarcopenia, more frequent in females. Low HGS was associated with a higher prevalence of falls. Only females with sarcopenia had lower bone mineral content.

Obesidad central, sarcopenia y conductas sedentarias en el riesgo cardiovascular por score Framingham y área total de placa carotídea / Central Obesity, Sarcopenia, and Sedentary Behaviors Related to Cardiovascular Risk by Framingham Score and Total Carotid Plaque Area

Resumen Antecedentes: las enfermedades cardiovasculares son la principal causa de morbimortalidad mundial. La obesidad, sarcopenia, actividad física insuficiente y las conductas sedentarias impactan de manera sinérgica en el riesgo cardiovascular. Objetivo: evaluar el riesgo cardiovascular en relación con la actividad física, las conductas sedentarias y la composición corporal. Materiales y métodos: estudio observacional transversal de 95 personas adultas de ambos sexos. Se determinó el riesgo cardiovascular mediante el score de Framingham y el score de Framingham corregido por área total de placa aterosclerótica; la composición corporal, por antropometría, bioimpedancia y dinamometría como indicador indirecto; y la actividad física y las conductas sedentarias, por cuestionario validado. Se condujeron análisis descriptivos, de correlación y asociación con un 95 % de confianza. Resultados: el 95 % de las mujeres y el 98 % de los varones presentaron riesgo cardiovascular elevado; el 51,5 %, obesidad; el 95,5%, obesidad central; y el 47,3 %, fuerza muscular disminuida. Se observaron asociaciones positivas significativas entre riesgo cardiovascular y circunferencia de cintura (rho=0,26; p=0,024). No hubo asociación significativa entre la fuerza muscular y el riesgo cardiovascular (rho=-0,21; p=0,065). La conducta sedentaria tuvo un efecto promotor del riesgo cardiovascular (OR=3,9; p=0,033). Conclusiones: la obesidad central y permanecer más de 6/h día en posición sedente son factores asociados al riesgo cardiovascular.

Abstract Background: Cardiovascular diseases are the principal cause of morbidity and mortality worldwide. Obesity, sarco-penia, insufficient physical activity, and sedentary behaviors synergistically impact cardiovascular risk. Objective: Evaluate cardiovascular risk in relation to physical activity, sedentary behaviors, and body composition. Materials and Methods: Cross-sectional observational study in 95 total males and females. Cardiovascular risk was determined using the Framingham score, which corrects for total area of atherosclerotic plaque. Risk was also determined using body composition, anthropometry, bioimpedance and dynamometry as indirect indicators, physical activity, sedentary behaviors, and a validated questionnaire. Descriptive, correlation and association analyses were conducted with 95% confidence. Results: 95% of women and 98% of men presented with an elevated cardiovascular risk; 51.5% with obesity, 95.5% central obesity, and 47.3% with diminished muscular strength. Significant positive associations were observed between cardiovascular risk and waist circumference (rho=0.26; p=0.024). There was no significant association between muscle strength and cardiovascular risk (rho=-0.21, p=0.065). Sedentary behavior increased cardiovascular risk (OR=3.9; p=0.033). Conclusions: Central obesity and staying more than six hours per day in a sitting position are factors associated with cardiovascular risk.

Acciones óseas de las hormonas de la neurohipófisis / Bone actions of neuro hypophyseal hormones

La oxitocina (OXT) como la arginina-vasopresina (AVP) son dos hormonas primitivas secretadas por la hipófisis posterior. Sus receptores están mucho más ampliamente distribuidos en el organismo de lo que se pensaba originalmente, incluido el hueso. En los estudios preclínicos, la OXT ha mostrado ser anabólica para el hueso, promoviendo la osteogénesis sobre la adipogénesis y favoreciendo la actividad osteoblástica sobre la osteoclástica. Tanto los osteoblastos como los osteoclastos tienen receptores para la OXT, y los efectos de los estrógenos sobre la masa ósea en ratones está mediada por lo menos en parte por la OXT. El mecanismo preciso por el cual la activación de los receptores de oxitocina (OXTR) se traduce en un incremento de la formación ósea permanece poco claro. La AVP también podría afectar el esqueleto en forma directa. Dos de los receptores de la AVP, V1a y V2 están expresados en osteoblastos y osteoclastos. La inyección de AVP en ratones de tipo salvaje aumenta la formación osteoclastos que producen resorción y reduce los osteoblastos formadores de hueso. En forma opuesta, la exposición de precursores osteoblásticos a antagonistas de los receptores V1a o V2, incrementan la osteoblastogénesis, como también lo hace la deleción genética del receptor V1a. (AU)

Both oxytocin (OXT) and argininevasopressin (AVP) are primitive hormones secreted by the posterior pituitary gland. OXT receptors are much more widely distributed in the body than originally thought, including in bone. In preclinical studies, OXT has been shown to be anabolic for bone, promoting osteogenesis over adipogenesis and favoring osteoblastic over osteoclastic activity. Both osteoblasts and osteoclasts have receptors for OXT, and the effects of estrogen on bone mass in mice is mediated at least in part by OXT. The precise mechanism by which the activation of oxytocin receptors (OXTRs) results in an increase in bone formation remains unclear. AVP could also have direct actions on the skeleton. The two AVP receptors, V1a and V2, are expressed in osteoblasts and osteoclasts. Injection of AVP in wild-type mice increases the formation of osteoclasts increasing bone resorption, and reduces bone-forming osteoblasts. On the contrary, the exposure of osteoblastic precursors to V1a and V2 antagonists increase osteoblastogenesis, the same as the genetic deletion of the V1a receptor. (AU)

Chronicity of Uncorrected Hyponatremia and Clinical Outcomes in Older Patients Undergoing Hip Fracture Repair.

Background: Chronic hyponatremia is a risk factor for hip fracture but remains uncorrected in most patients. This study evaluated if preoperative chronicity of uncorrected hyponatremia influences outcomes after hip fracture repair. Materials and Methods: Evaluated were older patients hospitalized for hip fracture repair between 2007 and 2012 with plasma sodium measured at admission and ≥1 preadmission outpatient measurement. Patients were classified as being normonatremic (NN; plasma sodium 135-145 mmol/L), chronic prolonged hyponatremia (CPH; ≥2 consecutive plasma sodium values <135 mmol/L over >90 days), or recent hyponatremia (one plasma sodium <135 mmol/L within 30 days before admission with previously normal plasma sodium). Length of hospital stay, in-hospital death, post-operative complications, 30-day readmission, and long-term mortality were the evaluated outcomes. Multivariable Cox regression was used to evaluate the association of hyponatremia status with outcomes. Results: Among 1,571 eligible patients, 76.7% were NN, 14% had CPH, and 9.1% had RH. Compared with NN patients, CHN patients were older and had more prior heart failure, alcoholism, and anticonvulsant drug use. In multivariable analyses, neither CPH or RH was associated with hospital length of stay, in-hospital or 30-day death, or 30-day readmission, while RH was associated with post-operative sepsis [adjusted odds ratio (aOR) 1.84, 95% CI: 1.01-3.35). Only CPH was independently associated with long-term all-cause death (OR 1.53, 95% CI: 1.12-2.09). Conclusions: Hyponatremia affects nearly 25% of patients undergoing hip fracture repair. Preoperative chronic untreated hyponatremia is associated with increased post-operative mortality following surgical repair of a hip fracture in older patients. Future studies should evaluate if correction of hyponatremia could decrease long-term mortality after hip fracture repair.