Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.

Calcification is a process of accumulation of calcium in tissues and deposition of calcium salts by the crystallization of PO43- and ionized calcium (Ca2+). It is a crucial process in the development of bones and teeth. However, pathological calcification can occur in almost any soft tissue of the organism. The better studied is vascular calcification, where calcium salts can accumulate in the intima or medial layer or in aortic valves, and it is associated with higher mortality and cardiovascular events, including myocardial infarction, stroke, aortic and peripheral artery disease (PAD), and diabetes or chronic kidney disease (CKD), among others. The process involves an intricate interplay of different cellular components, endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and pericytes, concurrent with the activation of several signaling pathways, calcium, Wnt, BMP/Smad, and Notch, and the regulation by different molecular mediators, growth factors (GFs), osteogenic factors and matrix vesicles (MVs). In the present review, we aim to explore the cellular players, molecular pathways, biomarkers, and clinical treatment strategies associated with vascular calcification to provide a current and comprehensive overview of the topic.

Human monkeypox virus in a tertiary hospital in Madrid, Spain: An observational study of the clinical and epidemiological characteristics of 53 cases.

A new outbreak of monkeypox virus (MPXV) infection, a zoonotic infection endemic in Central and West Africa, is spreading throughout the world with new epidemiology and clinical features. Our aim was to characterize patients presenting to Dermatology emergency room with a MPXV infection between 15 May and 30 June 2022 in a tertiary hospital in Madrid, Spain. We collected 53 patients and describe their clinical, demographic and epidemiological characteristics and followed their evolution. Most of the patients were men who had sex with men with high-risk sexual practices and no recent travels abroad. Most of them (91%) had had a sexually transmitted infection before. All patients had typical skin lesions consisting of vesicular-pustular rash with central umbilication which was localized or disseminated. The most frequent extracutaneous symptoms were fever, painful regional lymphadenopathy and asthenia. Proctitis was present in more than one third of patients. All patients were diagnosed by real time polymerase chain reaction of samples obtained from skin lesions. Pharyngeal and/or rectal exudates demonstrated MPXV in 74% of patients. The current worldwide outbreak of MPXV infections shows epidemiological and clinical differences from previous ones. Clinicians should be aware of these characteristics to correctly diagnose this emerging disease.

An Exceptional Case of Light Chain Only Variant of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits Secondary to Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

We present the case of an 86-year-old Caucasian male with an 11-year history of low-grade chronic lymphocytic leukemia (CLL) presenting with nephrotic syndrome (NS). Renal biopsy findings showed a diffuse mesangial and endocapillary proliferative glomerulonephritis (GN) lesion with fine granular deposits, consistent with a rare morphologic variant of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID)-lambda light chain (LC) only. Monthly combination therapy of rituximab (500 mg/m2 on day 1), fludarabine (30 mg/m2 on days 1-3), and cyclophosphamide (750 mg/m2 on days 1-3) was administered. Five courses of this regimen resulted in hematological remission, as well as a partial renal response with a reduction in the spot urine protein-to-creatinine ratio (UPCR) of 815.3 mg/g (reduction > 50% proteinuria without improvement in kidney function). This condition is a rare morphological variant of PGNMID, poorly described in CLL patients. We review the literature and suggest that this case provides sheds light on the unknown pathophysiological mechanisms of monoclonal immunoglobulins (MIg)-mediated glomerular damage in CLL patients, and may be helpful for the investigation of a more effective treatment.

The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection.

Background: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium <135 mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyse the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. Methods: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. Results: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96 h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio 0.165; 95% confidence interval: 0.018-0.686; p = 0.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, p = 0.041). Conclusion: We conclude that persistence of hyponatremia at 72-96 h of hospital admission was associated with higher mortality in patients with SARS-Cov-2.

Introduccion: La infección por SARS-CoV-2 se asocia con frecuencia con hiponatremia (sodio plasmático <135 mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20­37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario, y determinar la asociación de dicha hiponatremia con el pronóstico del COVID-19. Material y método: Estudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia, en el periodo marzo-mayo 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia al momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta. Resultados: 91 pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72­96 horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (OR 0,165; 95% intervalo de confianza: 0,018­0,686; p = 0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente, p = 0,041). Conclusiones: La persistencia de la hiponatremia tras las primeras 72­96 horas del ingreso hospitalario fue asociada a mayor mortalidad+- en los pacientes con SARS-Cov-2.

Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2) / The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection

IntroducciónLa infección por el coronavirus del síndrome respiratorio agudo grave de tipo 2 (SARS-CoV-2) se asocia con frecuencia con hiponatremia (sodio plasmático<135mmol/l), relacionándose con peor pronóstico. La incidencia de la hiponatremia se estima en 20-37% según las series, pero no existen datos sobre el pronóstico tras la corrección de la hiponatremia. Por ello, nuestros objetivos fueron: analizar la incidencia y gravedad de la hiponatremia al ingreso hospitalario y determinar la asociación de dicha hiponatremia con el pronóstico de la enfermedad por coronavirus de 2019 (COVID-19).Material y métodoEstudio de cohorte observacional y retrospectivo. Se incluyeron pacientes que ingresaron con diagnóstico de infección por COVID-19 e hiponatremia en el periodo marzo-mayo de 2020. Registramos variables epidemiológicas, demográficas, clínicas, analíticas y radiológicas de la infección por SARS-CoV-2 e hiponatremia en el momento del diagnóstico y durante la hospitalización. El seguimiento clínico comprendió desde el ingreso hasta el exitus o el alta.ResultadosNoventa y un pacientes (21,8%) de los 414 ingresados por infección del SARS-CoV-2 presentaron hiponatremia (81,32% hiponatremia leve, 9,89% moderada y 8,79% grave). La ausencia de corrección de la hiponatremia a las 72-96horas del ingreso hospitalario estuvo asociado a mayor mortalidad en los pacientes con COVID-19 (odds ratio 0,165; 95% intervalo de confianza: 0,018-0,686; p=0,011). Fallecieron 19 pacientes (20,9%). Se observó un aumento de la mortalidad en pacientes con hiponatremia grave en comparación con hiponatremia moderada y leve durante el ingreso (37,5% versus 11,1% versus 8,1%, respectivamente; p=0,041).ConclusionesLa persistencia de la hiponatremia tras las primeras 72-96horas del ingreso hospitalario se asoció a mayor mortalidad en los pacientes con SARS-CoV-2. (AU)

IntroductionSARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20–37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19.Material and methodObservational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March–May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge.Results91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72–96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041).ConclusionsWe conclude that persistence of hyponatremia at 72–96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2. (AU)

Assessing risk of vector transmission of Chagas disease through blood source analysis using LC-MS/MS for hemoglobin sequence identification.

Chagas disease is mainly transmitted by triatomine insect vectors that feed on vertebrate blood. The disease has complex domiciliary infestation patterns and parasite transmission dynamics, influenced by biological, ecological, and socioeconomic factors. In this context, feeding patterns have been used to understand vector movement and transmission risk. Recently, a new technique using Liquid chromatography tandem mass spectrometry (LC-MS/MS) targeting hemoglobin peptides has showed excellent results for understanding triatomines' feeding patterns. The aim of this study was to further develop the automated computational analysis pipeline for peptide sequence taxonomic identification, enhancing the ability to analyze large datasets data. We then used the enhanced pipeline to evaluate the feeding patterns of Triatoma dimidiata, along with domiciliary infestation risk variables, such as unkempt piles of firewood or construction material, cracks in bajareque and adobe walls and intradomiciliary animals. Our new python scripts were able to detect blood meal sources in 100% of the bugs analyzed and identified nine different species of blood meal sources. Human, chicken, and dog were the main blood sources found in 78.7%, 50.4% and 44.8% of the bugs, respectively. In addition, 14% of the bugs feeding on chicken and 15% of those feeding on dogs were captured in houses with no evidence of those animals being present. This suggests a high mobility among ecotopes and houses. Two of the three main blood sources, dog and chicken, were significantly (p < 0.05) affected by domiciliary infestation risk variables, including cracks in walls, construction material and birds sleeping in the intradomicile. This suggests that these variables are important for maintaining reproducing Triatoma dimidiata populations and that it is critical to mitigate these variables in all the houses of a village for effective control of these mobile vectors.

A multidisciplinary, collaborative, inter-agency and comprehensive approach for the control of Chagas Disease as a public health problem in Guatemala.

The Pan American Health Organization (PAHO) has defined Chagas Disease hotspots in Central America associated with the vector Triatoma spp. Triatoma dimidiata is a native vector adapted to multiple environments, including intra-domestic and peri-domestic habitats. A multi-institutional project named "Alliances for the elimination of Chagas in Central America" was created to help reduce the incidence of the disease in the region. Activities performed in the field as part of the project included aspects of vector surveillance and control, improvement of houses, diagnosis and treatment of individuals, health promotion, training of human resources and identification of access barriers to diagnosis and treatment. As a base line study, eleven villages, comprised of 1,572 households, were entomologically evaluated (83.4% overall participation); five were found to have very high infestation rates (>20%), three had high infestation rates (8-20%) and three had low-infestation rates (<8%), coinciding with the category of infestation-risk of the houses within each village. Serological tests were carried out in 812 people (>80% participation) in two of the 11 villages and none of the 128 children tested, less than 5 years of age, were positive for Trypanosoma cruzi infection. Community participation in all the activities was high (>70%). The collaboration between several subnational, national, and international institutions, each with specific roles, promoted community participation in the activities of vector control and patient care, thus, establishing a baseline to continue implementing and monitoring project progress.

The impact of the correction of hyponatremia during hospital admission on the prognosis of SARS-CoV-2 infection. / Impacto de la corrección temprana de la hiponatremia en el pronóstico de la infección del síndrome respiratorio agudo grave del coronavirus 2 (SARS-CoV-2).

INTRODUCTION: SARS-CoV-2 infection is frequently associated with hyponatremia (plasma sodium<135mmol/L), being associated with a worse prognosis. The incidence of hyponatremia is estimated to be 20-37% according to the series, but there are no data on the prognosis after correction of hyponatremia. Therefore, our objectives were: to analyze the incidence and severity of hyponatremia at hospital admission, and to determine the association of this hyponatremia with the prognosis of COVID-19. MATERIAL AND METHOD: Observational and retrospective cohort study. Patients who were admitted with a diagnosis of COVID-19 infection and hyponatremia, in the period March-May 2020, were included. We recorded epidemiological, demographic, clinical, biochemical, and radiological variables of SARS-CoV-2 infection and hyponatremia at the time of diagnosis and during hospitalization. The clinical follow-up ranged from admission to death or discharge. RESULTS: 91 patients (21.8%) of the 414 admitted for SARS-CoV-2 infection presented hyponatremia (81.32% mild hyponatremia, 9.89% moderate and 8.79% severe). The absence of correction of hyponatremia 72-96h after hospital admission was associated with higher mortality in patients with COVID-19 (Odds Ratio .165; 95% confidence interval: .018-.686; P=.011). 19 patients (20.9%) died. An increase in mortality was observed in patients with severe hyponatremia compared with moderate and mild hyponatremia during hospital admission (37.5% versus 11.1% versus 8.1%, P=.041). CONCLUSIONS: We conclude that persistence of hyponatremia at 72-96h of hospital admission was associated with higher mortality in patients with SARS-CoV-2.

Improving Adherence to Myofunctional Therapy in the Treatment of Sleep-Disordered Breathing.

Myofunctional therapy (MT) is used to treat sleep-disordered breathing. However, MT has low adherence-only ~10% in most studies. We describe our experiences with MT delivered through a mobile health app named Airway Gym®, which is used by patients who have rejected continuous positive airway pressure and other therapies. We compared ear, nose, and throat examination findings, Friedman stage, tongue-tie presence, tongue strength measured using the Iowa oral performance instrument (IOPI), and full polysomnography before and after the 3 months of therapy. Participants were taught how to perform the exercises using the app at the start. Telemedicine allowed physicians to record adherence to and accuracy of the exercise performance. Fifty-four patients were enrolled; 35 (64.8%) were adherent and performed exercises for 15 min/day on five days/week. We found significant changes (p < 0.05) in the apnoea-hypopnoea index (AHI; 32.97 ± 1.8 to 21.9 ± 14.5 events/h); IOPI score (44.4 ± 11.08 to 49.66 ± 10.2); and minimum O2 saturation (80.91% ± 6.1% to 85.09% ± 5.3%). IOPI scores correlated significantly with AHI after the therapy (Pearson r = 0.4; p = 0.01). The 19 patients who did not adhere to the protocol showed no changes. MT based on telemedicine had good adherence, and its effect on AHI correlated with IOPI and improvement in tongue-tie.

Patiromer in a Patient with Severe Hyperkalemia on Incremental Hemodialysis with 1 Session per Week: A Case Report and Literature Review.

Hyperkalemia is common in patients with ESRD, undergoing hemodialysis (HD), and is associated with an increase in hospitalization and mortality. Residual kidney function in long-term dialysis patients is associated with lower morbidity and mortality in HD patients. Although the 2015 National Kidney Foundation-Kidney Disease Outcomes Quality Initiate (NKD-KDOQI) guidelines allow the reduction in the weekly HD dose for patients with a residual kidney urea clearance (Kur) >3 mL/min/1.73 m2, very few centers adjust the dialysis dose based on these criteria. In our center, the pattern of incremental hemodialysis (iHD) with once-a-week schedule (1 HD/W) has been an option for a group of patients showing very good results. This pattern is maintained as long as residual diuresis is >1,000 mL/24 h, Kur is >4 mL/min, and there is no presence of edema or volume overload, as well as no analytical parameters persistently outside the advisable range (serum phosphorus >6 mg/dL or potassium [K+] >6.5 mmol/L). Management of hyperkalemia in HD patients includes reduction of dietary intake, dosing of medications that contribute to hyperkalemia, and use of cation-exchange resins such as calcium or sodium polystyrene sulfonate. Two newer potassium binders, patiromer sorbitex calcium and sodium zirconium cyclosilicate, have been safely used for potassium imbalance treatment in patients with ESRD in HD with a conventional regimen of thrice weekly, but has not yet been studied in 1 HD/W schedules. We present the case of a 76-year-old woman in iHD (1 HD/W) treated with patiromer for severe HK and describe her clinical characteristics and outcomes. In addition, we review the corresponding literature. Based on these data, it can be anticipated that the use of patiromer may overcome the risk of hyperkalemia in patients with incident ESRD treated with less-frequent HD regimens.