Efficacy and safety of hydroxychloroquine for treatment of mild SARS-CoV-2 infection and prevention of COVID-19 severity in pregnant and postpartum women: A randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Pregnant women have an increased risk of severe COVID-19. Evaluation of drugs with a safety reproductive toxicity profile is a priority. At the beginning of the pandemic, hydroxychloroquine (HCQ) was recommended for COVID-19 treatment. MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in eight teaching hospitals in Spain to evaluate the safety and efficacy of HCQ in reducing viral shedding and preventing COVID-19 progression. Pregnant and postpartum women with a positive SARS-CoV-2 PCR (with or without mild COVID-19 signs/symptoms) and a normal electrocardiogram were randomized to receive either HCQ orally (400 mg/day for 3 days and 200 mg/day for 11 days) or placebo. PCR and electrocardiogram were repeated at day 21 after treatment start. Enrollment was stopped before reaching the target sample due to low recruitment rate. Trial registration EudraCT #: 2020-001587-29, on April 2, 2020. CLINICAL TRIALS: gov # NCT04410562, registered on June 1, 2020. RESULTS: A total of 116 women (75 pregnant and 41 post-partum) were enrolled from May 2020 to June 2021. The proportion of women with a positive SARS-CoV-2 PCR at day 21 was lower in the HCQ group (21.8%, 12/55) than in the placebo group (31.6%, 18/57), although the difference was not statistically significant (P = 0.499). No differences were observed in COVID-19 progression, adverse events, median change in QTc, hospital admissions, preeclampsia or poor pregnancy and perinatal outcomes between groups. CONCLUSIONS: HCQ was found to be safe in pregnant and postpartum women with asymptomatic or mild SARS-CoV-2 infection. Although the prevalence of infection was decreased in the HCQ group, the statistical power was insufficient to confirm the potential beneficial effect of HCQ for COVID-19 treatment.

Design of a postpartum hemorrhage and transfusion risk calculator.

Background: Postpartum hemorrhage is the major cause of maternal deaths due to childbirth and also responsible for maternal morbidity. Objectives: In this study we set out to look the incidence of postpartum hemorrhage in our population, to identify the most important risk factors for postpartum hemorrhage and thus develop a predictive risk calculator for postpartum hemorrhage and transfusion. Study design: data was taken from patients who presented vaginal delivery or cesarean section from January 1 to December 31, 2016, the variables taken into account as risk factors were as follows: Gestational age, history of chronic or gestational hypertension, preeclampsia, previous abortions, parity, previous cesarean section, placenta previa, labor time, and postpartum hemorrhage as the event of interest. An objective quantification was performed on a weight scale in grams for the estimation of bleeding, considering postpartum hemorrhage those with >500 ml in vaginal delivery and >1000 ml of blood loss in cesarean section. Subsequently, a predictive risk calculator was developed using the Naïve Bayes algorithm. Results: A success rate of 58% was obtained in the identification of patients at high risk of hemorrhage, and 36% for transfusion, with a sensitivity of 50.7% and specificity of 64.06%, identifying as risk factors for postpartum hemorrhage gestational age between 35 and 40 weeks, hypertension and preeclampsia, previous cesarean section, duration of labor <1 h or more than 10 h, placenta previa and previous history of postpartum hemorrhage. Conclusion: A postpartum hemorrhage risk calculator has been designed, which due to its improved accuracy after incorporation of data becomes a useful tool that will require a larger study population to improve its performance in clinical practice and more similar studies to validate it.

Porcine model of neurocysticercosis by intracarotid injection of Taenia solium oncospheres: Dose assessment, infection outcomes and serological responses.

BACKGROUND: Neurocysticercosis (NCC) is the infection of the human central nervous system (CNS) by Taenia solium larvae that cause significant neurological morbidity. Studies on NCC pathophysiology, host-parasite interactions or therapeutic agents are limited by the lack of suitable animal models. We have previously reported that carotid injection of activated T. solium oncospheres directs parasites into the CNS and consistently reproduces NCC. This study assessed the minimal dose required to consistently obtain NCC by intracarotid oncosphere injection and compared antigen and antibody response profiles by dose-group. METHODS/PRINCIPAL FINDINGS: Three groups of pigs were infected with either 2500 (n = 10), 5000 (n = 11), or 10000 (n = 10) oncospheres. Two pigs died during the study. Necropsy exam at day 150 post-infection (PI) demonstrated viable NCC in 21/29 pigs (72.4%), with higher NCC rates with increasing oncosphere doses (4/9 [44.4%], 9/11 [81.8%] and 8/9 [88.9%] for 2500, 5000, and 10000 oncospheres respectively, P for trend = 0.035). CNS cyst burden was also higher in pigs with increasing doses (P for trend = 0.008). Viable and degenerated muscle cysticerci were also found in all pigs, with degenerated cysticerci more frequent in the 2500 oncosphere dose-group. All pigs were positive for circulating parasite antigens on ELISA (Ag-ELISA) from day 14 PI; circulating antigens markedly increased at day 30 PI and remained high with plateau levels in pigs infected with either 5000 or 10000 oncospheres, but not in pigs infected with 2500 oncospheres. Specific antibodies appeared at day 30 PI and were not different between dose-groups. CONCLUSION/SIGNIFICANCE: Intracarotid injection of 5000 or more oncospheres produces high NCC rates in pigs with CNS cyst burdens like those usually found in human NCC, making this model appropriate for studies on the pathogenesis of NCC and the effects of antiparasitic treatment.

Application of pelvic floor ultrasound during pregnancy to detect patients at risk of cesarean section due to failure of labor progression in a Spanish population.

OBJECTIVE: Our study is aimed at evaluating the characteristics of the pelvic floor, assessed through transperineal ultrasound, since it may influence or increase the possibility of having a cesarean delivery, with the objective of acting on those variables that can be modified during pregnancy. STUDY DESIGN: Transperineal ultrasound was performed on 109 primiparous pregnant women in their first trimester of pregnancy, recruited between May 2018 and February 2019, with the purpose of studying the hiatus area at rest, retention and Valsalva. We have reassessed them at the end of pregnancy and delivery data were recorded. We selected 8 patients as case-study, who had cesarean section delivery due to failure of labor progression. We selected 4 control-cases for each, reaching the total of 32 controls, with similar age and body mass index, to avoid obtaining a biased result from these data. RESULTS: In the study of hiatal areas, patients who delivered by cesarean section had a smaller hiatal area at rest, during levator ani muscle contraction and during Valsalva maneuver, at all visits. In early pregnancy, the range of the resting hiatal area was 13.8 ± 2.0 cm2 for cesarean sections, compared to 16.2 ± 2.7 cm2 for vaginal deliveries with an OR of 0.57 (0.34-0.95, 95% CI). For hiatal area on Valsalva, the OR was 0.55 (0.35-0.88, 95% CI). Therefore, the smaller the hiatal area, the greater the possibility of cesarean section. At the end of pregnancy, between 34 and 36 weeks of gestation, the OR of hiatal area on Valsalva was 0.78 (0.60-1.00, 95% CI). CONCLUSION: The hiatus area measured by transperineal ultrasonography at the beginning and at the end of the pregnancy may be useful to identify the patients who are at a higher risk of cesarean delivery due to failure of labor progression.

Metabolic impact of current therapeutic strategies in Polycystic Ovary Syndrome: a preliminary study.

PURPOSE: To investigate the metabolic impact of currently used therapies in polycystic ovary syndrome (PCOS). METHODS: This is an observational, retrospective and transversal protocol. A small cohort of 133 patients, aged 14-48 years, diagnosed with PCOS was divided into four experimental groups: 1) untreated PCOS patients (n = 51); 2) PCOS patients treated with one of the following therapies (n = 82): a) combined oral contraceptives (COC, n = 35); b) metformin (n = 11); and c) inositols (n = 36). RESULTS: Although only < 10% of patients included in this cohort can be strictly encompassed in the development of metabolic syndrome, approximately 20% had insulin resistance. In PCOS patients, COC treatment modified the hormonal profile and worsened lipid parameters (increasing cholesterol and triglyceride levels) and insulin resistance, whereas inositol therapies improved significantly insulin resistance and glycosylated hemoglobin, reducing cholesterol and triglyceride levels. In these women, obesity was associated with greater alterations in lipid and glycemic metabolism and with higher blood pressure levels. PCOS patients with phenotype A presented vaster alterations in lipid metabolism and higher values of glycosylated hemoglobin as well as blood pressure compared to other PCOS phenotypes. CONCLUSIONS: Results in this paper suggest that inositol therapies (alone or combined with COC) are the most useful therapies with the best benefits against PCOS symptoms. Thus, integrative treatment may become a more efficient long-term choice to control PCOS symptoms. Furthermore, obesity can be considered as an adverse symptom and calorie restriction a key element of combined treatment in PCOS, not only for fertility management but also in long-term metabolic sequelae.

Hydroxychloroquine efficacy and safety in preventing SARS-CoV-2 infection and COVID-19 disease severity during pregnancy (COVID-Preg): a structured summary of a study protocol for a randomised placebo controlled trial.

OBJECTIVES: The primary objectives of the study are: 1. To assess the effect of hydroxychloroquine (HCQ) in reducing SARS-CoV-2 viral shedding by PCR in infected pregnant women with mild symptoms. 2. To assess the efficacy of HCQ to prevent SARS-CoV-2 infection in pregnant women in contact with an infected or suspected case. 3. To evaluate the effect of HCQ in preventing the development of the COVID-19 disease in asymptomatic SARS-CoV-2-infected pregnant women. The secondary objectives are: 1. To determine the effect of HCQ on the clinical course and duration of the COVID-19 disease in SARS-CoV-2-infected pregnant women. 2. To determine the impact of HCQ on the risk of hospitalization and mortality of SARS-CoV-2-infected pregnant women. 3. To assess the safety and tolerability of HCQ in pregnant women. 4. To describe the clinical presentation of SARS-CoV-2 infection during pregnancy. 5. To describe the effects of maternal SARS-CoV-2 infection on pregnancy and perinatal outcomes by treatment group. 6. To determine the risk of vertical transmission (intra-utero and intra-partum) of SARS-CoV-2. TRIAL DESIGN: Randomized double-blind placebo-controlled two-arm multicentre clinical trial to evaluate the safety and efficacy of HCQ to prevent and/or minimize SARS-CoV-2 infection during pregnancy. Participants will be randomized to receive a 14-day oral treatment course of HCQ or placebo, ratio 1:1. PARTICIPANTS: Study population: pregnant women undergoing routine prenatal follow up or attending emergency units at the participating hospitals who report either symptoms/signs suggestive of COVID-19 disease or close contact with a suspected or confirmed COVID-19 case. Inclusion criteria Women will be invited to participate in the trial and sign an informed consent if they meet the following inclusion criteria. • Presenting with fever (≥37.5°C) and/or one mild symptom suggestive of COVID-19 disease (cough, dyspnoea, chills, odynophagia, diarrhoea, muscle pain, anosmia, dysgeusia, headache) OR being contact* of a SARS-CoV-2 confirmed or suspected case in the past 14 days • More than 12 weeks of gestation (dated by ultrasonography) • Agreement to deliver in the study hospitals Exclusion criteria • Known hypersensitivity to HCQ or other 4-amonoquinoline compounds • History of retinopathy of any aetiology • Concomitant use of digoxin, cyclosporine, cimetidine • Known liver disease • Clinical history of cardiac pathology including known long QT syndrome • Unable to cooperate with the requirements of the study • Participating in other intervention studies • Delivery onset (characterized by painful uterine contractions and variable changes of the cervix, including some degree of effacement and slower progression of dilatation up to 5 cm for first and subsequent labours) The study participants will be stratified by clinical presentation and SARS-CoV-2 PCR results. Assignment of participants to study groups will be as follows: • SARS-CoV-2-PCR confirmed, infected pregnant women: a. symptomatic (n=100) b. asymptomatic (n=100) • SARS-CoV-2 PCR negative pregnant women in contact* with a SARS-CoV-2-infected confirmed or suspected case (n=514). *The ECDC definition of close contact will be followed. The trial will be conducted in five hospitals in Spain: Hospital Clínic of Barcelona, Hospital Sant Joan de Déu and Hospital de la Santa Creu i Sant Pau, in Barcelona, and HM Puerta del Sur and Hospital Universitario de Torrejón, in Madrid. INTERVENTION AND COMPARATOR: Participants will be randomized to HCQ (400 mg/day for three days, followed by 200 mg/day for 11 days) or placebo (2 tablets for three days, followed by one tablet for 11 days). MAIN OUTCOMES: The primary outcome is the number of PCR-confirmed infected pregnant women assessed from collected nasopharyngeal and oropharyngeal swabs at day 21 after treatment start (one week after treatment is completed). RANDOMISATION: Allocation of participants to study arms will be done centrally by the trial's Sponsor (the Barcelona Institute for Global Health, ISGlobal) by block randomization. This method will ensure balanced allocation to both arms. The electronic CRF will automatically assign a study number to each participant, depending on her study group and recruitment site. Each number will be related to a treatment number, which assigns them to one of the study arms. BLINDING (MASKING): Participants, caregivers, investigators and those assessing the outcomes will be blinded to group assignment. Study tablets (HCQ and placebo) will be identically packaged in small opaque bottles. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): This study requires 200 SARS-CoV-2 infected and 514 contact pregnant women, randomised 1:1 with 100 and 227 respectively in each study arm. TRIAL STATUS: Protocol version 1.0, from May 8th, 2020. Recruitment is ongoing (first patient recruited the 19th May 2020 and recruitment end anticipated by December 2020). TRIAL REGISTRATION: EudraCT number: 2020-001587-29, registered 2 April 2020. Clinicaltrials.gov identifier: NCT04410562 , retrospectively registered 1 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Immunogenicity, transplacental transfer of pertussis antibodies and safety following pertussis immunization during pregnancy: Evidence from a randomized, placebo-controlled trial.

BACKGROUND: Pertussis immunization during pregnancy is recommended in many countries. Data from large randomized controlled trials are needed to assess the immunogenicity, reactogenicity and safety of this approach. METHODS: This phase IV, observer-blind, randomized, placebo-controlled, multicenter trial assessed immunogenicity, transplacental transfer of maternal pertussis antibodies, reactogenicity and safety of a reduced-antigen-content diphtheria-tetanus-three-component acellular pertussis vaccine (Tdap) during pregnancy. Women received Tdap or placebo at 27-36 weeks' gestation with crossover ≤ 72-hour-postpartum immunization. Immune responses were assessed before the pregnancy dose and 1 month after, and from the umbilical cord at delivery. Superiority (primary objective) was reached if the lower limits of the 95% confidence intervals (CIs) of the pertussis geometric mean concentration (GMC) ratios (Tdap/control) in cord blood were ≥ 1.5. Solicited and unsolicited adverse events (AEs) and pregnancy-/neonate-related AEs of interest were recorded. RESULTS: 687 pregnant women were vaccinated (Tdap: N = 341 control: N = 346). Superiority of the pertussis immune response (maternally transferred pertussis antibodies in cord blood) was demonstrated by the GMC ratios (Tdap/control): 16.1 (95% CI: 13.5-19.2) for anti-filamentous hemagglutinin, 20.7 (15.9-26.9) for anti-pertactin and 8.5 (7.0-10.2) for anti-pertussis toxoid. Rates of pregnancy-/neonate-related AEs of interest, solicited general and unsolicited AEs were similar between groups. None of the serious AEs reported throughout the study were considered related to maternal Tdap vaccination. CONCLUSIONS: Tdap vaccination during pregnancy resulted in high levels of pertussis antibodies in cord blood, was well tolerated and had an acceptable safety profile. This supports the recommendation of Tdap vaccination during pregnancy to prevent early-infant pertussis disease. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02377349.

A 42-Year-Old Woman with Untreated Growth Hormone Insensitivity, Diabetic Retinopathy, and Gene Sequencing Identifies a Variant of Laron Syndrome.

BACKGROUND Growth hormone insensitivity and reduced levels of insulin-like growth factor-1 (IGF-1) are associated with metabolic syndrome that includes obesity, hyperglycemia, type 2 diabetes mellitus, and dyslipidemia. Laron syndrome is a rare autosomal recessive condition associated with insensitivity to growth hormone that results in short stature and metabolic syndrome and is usually diagnosed in childhood. This report is of a 42-year-old Mexican woman with untreated growth hormone insensitivity and diabetic retinopathy, in whom gene sequencing supported the identification of a variant of Laron syndrome. CASE REPORT A 42-year-old Mexican woman with untreated growth hormone insensitivity, metabolic syndrome, and type 2 diabetes mellitus was diagnosed with cataracts, severe retinopathy and hearing loss. She was investigated for genetic causes of reduction in IGF-1. Next-generation sequencing (NGS) showed genetic changes in the growth hormone and IGF-1 axis. The patient's phenotype and genetic changes were consistent with Laron syndrome. CONCLUSIONS The early detection of reduced IGF-1 and identification of the cause of growth hormone insensitivity require international consensus on the approach to diagnosis and treatment methods, including effective IGF-1 replacement therapy. Early diagnosis may reduce the clinical consequences of complications that include short stature the development of metabolic syndrome, type 2 diabetes mellitus, and retinopathy.

Recomendaciones latinoamericanas para el manejo de la hipertensión arterial en adultos (RELAHTA 2)

RESUMEN Se presenta la segunda parte de las recomendaciones latinoamericanas para el manejo de la Hipertensión Arterial (HTA) en adultos. En una primera fase se han descripto los aspectos más relevantes de la epidemiología, aspectos fisiopatológicos, cómo hacer diagnóstico, pautas terapéuticas, urgencias y emergencias hipertensivas, poblaciones especiales, hipertensión refractaria y la aplicación de las guías en la vida real. En esta segunda parte, se emiten recomendaciones respondiendo a preguntas específicas para prevención primaria, secundaria, terciaria y cuaternaria. En general pocas recomendaciones al respecto del manejo de la hipertensión arterial surgen desde la clínica médica/ medicina interna, a pesar de dos situaciones: la mayoría de los pacientes con hipertensión arterial son evaluados y manejados por los clínicos, y la clínica médica es la especialidad que permite la mirada holística e integrada de los problemas de salud del adulto, permitiendo agregar el enfoque biográfico al biológico, comprender e interpretar no solo el problema de salud sino sus causas y consecuencias (que muchas veces suelen corresponder a diferentes parénquimas, lo cual en el modelo fragmentado haría transitar al paciente por distintas especialidades). El bajo porcentaje de pacientes hipertensos controlados obliga a todos los profesionales involucrados en el manejo de los mismos a optimizar recursos y detectar problemas que se asocien a un control deficitario como la sub utilización del tratamiento farmacológico, baja tasa de pacientes tratados con estrategia combinada (la mayoría de los pacientes actualmente recibe monoterapia), falta de prescripción adecuada de los cambios en el estilo de vida, baja adherencia terapéutica e inercia clínica. En la presente publicación se presentan recomendaciones efectuadas por especialistas en clínica médica / medicina interna para el manejo de la hipertensión arterial en adultos, respondiendo preguntas de prevención primaria, secundaria, terciaria, y cuaternaria.

ABSTRACT The second part of the Latin American recommendations for the management of Arterial Hypertension (HTA) in adults is presented. In a first phase, the most relevant aspects of epidemiology, physiopathological aspects, how to diagnose, therapeutic guidelines, hypertension emergencies, special populations, refractory hypertension and the application of guides in real life have been described. In this second part, recommendations are issued answering specific questions for primary, secondary, tertiary and quaternary prevention. In general, few recommendations regarding the management of arterial hypertension arise from the medical clinic / internal medicine, despite two situations: the majority of patients with hypertension are evaluated and managed by the clinicians, and the medical clinic is the specialty that allows the holistic and integrated look of the health problems in adults, allowing to add the biographical approach to the biological, to understand and interpret not only the health problem but its causes and consequences (which often correspond to different parenchyma, which in the fragmented model would make the patient move through different specialties). The low percentage of controlled hypertensive patients forces all the professionals involved in the management of them to optimize resources and detect problems that are associated with a deficit control such as the under utilization of pharmacological treatment, low rate of patients treated with combined strategy (the most patients currently receive monotherapy), lack of adequate prescription of changes in lifestyle, low therapeutic adherence and clinical inertia. This publication presents recommendations made by specialists in medical clinic/internal medicine for the management of hypertension in adults, answering primary, secondary, tertiary and quaternary prevention questions.

Un estudio sobre la utilidad de biomarcadores en infecciones ginecológicas / A study on the utility of biomarkers in gynecological infections

Objetivo: en este estudio se ha querido demostrar que dos biomarcadores ampliamente usados en el diagnóstico de patología infecciosa como son la leucocitosis y la proteína creactiva, también son útiles en la enfermedad inflamatoria pélvica ya que nos permiten establecer la gravedad de cada infección y comprobar la evolución de cada paciente una vez instaurado el tratamiento antibiótico. Método: se hizo un estudio analítico y retrospectivo de 26 pacientes con enfermedad inflamatoria pélvica ingresadas en el Hospital Madrid Monteprincipe, Hospital Madrid Sanchinarro y Hospital Madrid Torrelodones entre los años 2008 y 2012 y se analizaron los valores de ambos marcadores obtenidos en las analíticas de urgencias al ingreso y en las últimas antes del alta. Se realizó un test T de Student para muestras apareadas para leucocitosis (p = 0,000) y para proteína creactiva (p = 0,002), con diferencias estadísticamente significativas (p < 0,05) en ambos. Conclusión: tanto la leucocitosis como la proteína creactiva son útiles también como reflejo cuantitativo de la gravedad de la enfermedad inflamatoria pélvica y como indicador de respuesta al tratamiento (AU)

Objective: In this study we wanted to demonstrate that two biomarkers widely used in infectious pathology such as leukocytosis and C-reactive protein are also viable in pelvic inflamatory disease to quantify the severity of the infection and evaluate the response of each patient once the antibiotic treatment has been established. Method: We performed a retrospective analytical study of 26 patients with pelvic inflamatory disease admitted in Hospital Madrid Montepríncipe, Hospital Madrid Sanchinarro and Hospital Madrid Torrelodones between the years 2008 and 2012, and analyzed the values of both markers obtained before the admittance and in the latest tests before the discharge. Apaired samples T-Student test was performed for Leucocitosis (p = 0.000) and C-reactive protein (p = 0.002), with significant differences (p < 0.05). Conclusion: Both the leukocytosis and C-reactive protein are useful as a quantitative reflection of the severity of pelvic inflamatory disease and also as an indicator of the response to treatment (AU)

El papel de los triglicéridos en la aterosclerosis y su relación con la resistencia a la insulina: una ruta desconocida

Fue hace 30 años cuando la relación entre hipertrigliceridemia y la enfermedad de la arteria coronaria se postuló por primera vez y luego se confirmó en muchos artículos, así como en el estudio PROCAM. La condición de resistencia a la insulina tiene un perfil lipídico y la capacidad intestinal para producir quilomicrones postprandiales distintiva, que cada vez es más relevante. La absorción de colesterol es regulada por un portador (NPC1L1) cuya expresión está aumentada en los pacientes diabéticos y con resistencia a la insulina, que desempeña un papel importante en el origen de la dislipidemia postprandial, que es una respuesta fisiológica durante todo el día siempre que la ingesta oral-grasa supera la necesidad. Un gran número de estudios han demostrado que la dislipidemia postprandial contribuye al desarrollo de la aterosclerosis y la enfermedad de la arteria coronaria (CAD). Los pacientes obesos y diabéticos, así como aquellos con síndrome metabólico a menudo tienen dislipidemia postprandial. El paciente diabético se caracteriza esencialmente por tener niveles elevados de colesterol no-HDL en lugar de los altos niveles de LDL. Este no- HDL cuenta con acciones para muchas partículas aterogénicas, denominándose "riesgo residual" y que no está cubierto por el uso de las estatinas. Debido a todas estas pruebas, creemos que la normalización de la medición de los niveles de triglicéridos postprandiales debe ser pertinente con el fin de utilizar este parámetro como un factor de riesgo directamente relacionado con la patogénesis de la aterosclerosis y los eventos cardiovasculares.

It was 30 years ago when the relationship between hypertriglyceridemia and coronary artery disease was first postulated and then it was confirmed in many articles as well as in the PROCAM study. The insulin-resistance condition has a distinctive lipid profile and the intestinal ability to produce postprandial chylomicrons it´s becoming more relevant. Cholesterol absorption is regulated by a carrier (NPC1L1) whose expression is increased in diabetic and insulin-resistance patients and it plays an important role originating postprandial dyslipidemia, which is a physiological response throughout the day whenever the fatty oral intake exceeds the need of it. A large number of studies have shown that postprandial dyslipidemia contributes to developing atherosclerosis and coronary artery disease (CAD). Obese and diabetic patients as well as those with metabolic syndrome often have postprandial dyslipidemia. The diabetic patient is essentially characterized for having elevated levels of Non-HDL cholesterol rather than high levels of LDL. This Non-HDL share accounts for many atherogenic particles, it is called “Residual Risk” and it is not covered by the use of statins. Due to all these evidence we believe the standardization of measuring postprandial triglycerides levels to be pertinent in order to use this parameter as a risk factor directly related with the pathogenesis of atherosclerosis and cardiovascular events.

Disfunción beta pancreática

La disfunción beta pancreática es una realidad fisiopatológica que conduce a una pérdida gradual en la eficacia de los opciones terapéuticas utilizadas en la DM. La evidencia actual establece que tanto en los diabéticos como en la condición de prediabetes, la disfunción de la célula beta es el primer defecto demostrable con limitación de la capacidad de compensación en presencia de resistencia a la insulina. Cada vez toma más importancia la necesidad de mantener el control glucémico a largo plazo utilizando opciones terapéuticas que aseguren la preservación del funcionamiento de la masa beta pancreática.

The dysfunction pancreatic beta is a physiopatological reality that conducts to a gradual loss in the efficacy of the therapeutic options utilized in the DM. The current evidence establishes that so much in the diabetic as in the condition of prediabetes, the dysfunction of the cell beta is the first demonstrable defect with limitation of the capacity of clearing in the presence of resistance to the insulin. Each time takes more importance the need to maintain the control glucémico long-term utilizing therapeutic options that assure the preservation of the operation of the pancreatic mass.

[Protective effect of melatonin and sodium thiosulphate on histopathology and ultrastructure of the kidney in rats with acute paraquat poisoning]. / Efecto protector de la melatonina y el tiosulfato de sodio sobre la histopatología y la ultraestructura del riñon en ratas con intoxicación aguda por Paraquat.

Paraquat (PQ) toxicity produces severe injures in many major organs systems, including kidney, developing renal failure with fatal evolution in most of the cases. Several antidotes have been used in the treatment of paraquat intoxication without satisfactory results. The antioxidative effect of melatonin (MLT) and sodium thiosulphate (STS) on kidney in rats with acute intoxication by PQ was studied. Forty male Wistar rats were used, divided in 4 groups of 10 rats each. Group I, control, was injected intraperitoneally (ip) with 1 ml of saline solution; group II, received DL50 of PQ, ip; groups III and IV, DL50 of PQ, and simultaneously the first dose of MLT (15 mg/kg, ip) or STS (1,5 g/kg, i.p.) respectively. Thirty minutes later, groups III and IV received a second similar dose of MLT and TSS. After 24 hours, rats were sacrificed with pentobarbital, and kidneys were extracted for morphological study. Light and electronic microscopy observations showed in group II morphological changes of acute tubular necrosis in proximal tubule in group II, similar findings, with lesser magnitude, were observed in the animals treated with the antidotes, suggesting a partial protection. In conclusion, individual use of MLT and STS at the doses and time used partially prevent damage caused by paraquat to the cell. In consequence, more experiments with these drugs are necessary to considere them as specific treatments in cases of poisoning by paraquat.

Efecto protector de la melatonina y el tiosulfato de sodio sobre la histopatología y la ultraestructura del riñón en ratas con intoxicación aguda por paraquat / Protective effect of melatonin and sodium thiosulphate on histopathology and ultrastructure of the kidney in rats with acute intoxication for paraquat

La intoxicación aguda con paraquat (PQ) produce daños severos en muchos órganos, entre ellos el riñón, donde se desarrolla insuficiencia renal. Se han utilizado varios antídotos en el tratamiento de la intoxicación por PQ sin resultados satisfactorios. En este estudio se determinó el efecto protector de la melatonina (MLT) y el tiosulfato de sodio (TSS) sobre el riñón, en ratas con intoxicación aguda por paraquat. Se utilizaron 40 ratas Wistar, machos, divididas en 4 grupos de 10 ratas cada uno. Al grupo I, control, se le inyectó 1 ml de solución fisiológica, vía intraperitoneal (ip); el grupo II, recibió DL50 de PQ, ip; los grupos III y IV recibieron DL50 de PQ, y simultáneamente la primera dosis de MLT (15 mg/kg) o TSS (1,5 g/kg), respectivamente (ip). Treinta minutos después, los grupos III y IV recibieron otra dosis igual de MLT y TSS. A las 24 horas de tratadas las ratas fueron sacrificadas con pentobarbital, extrayéndose el riñon para su estudio morfológico. Con la microscopía de luz y electrónica, en el grupo II se evidenciaron cambios morfológicos de necrosis tubular aguda en el túbulo proximal; observándose hallazgos similares de menor intensidad en los animales tratados con los antídotos, sugiriendo una protección parcial. En conclusión, el uso individual de la MLT y TSS, en las dosis y plazo empleados, revierte parcialmente el daño que causa el paraquat a la célula. En consecuencia, son necesarias más evaluaciones de estas drogas para su uso clínico en el tratamiento de la intoxicación por paraquat.

[Acute cardiovascular beriberi (shoshin-beriberi)]. / Beriberi cardiovascular agudo (shoshin-beriberi).

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called "dry" beriberi (BB) to differentiate it from "wet" BB, with essentially cardiovascular manifestations. Wet can be either "classic" wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the "shoshin" BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered.

Beriberi cardiovascular agudo (shoshin-beriberi) / Acute cardiovascular beriberi (shoshin-beriberi)

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called "dry" beriberi (BB) to differentiate it from "wet" BB, with essentially cardiovascular manifestations. Wet can be either "classic" wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the "shoshin" BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered

Beriberi cardiovascular agudo (shoshin-beriberi) / Acute cardiovascular beriberi (shoshin-beriberi)

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called "dry" beriberi (BB) to differentiate it from "wet" BB, with essentially cardiovascular manifestations. Wet can be either "classic" wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the "shoshin" BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered (AU)

Beriberi cardiovascular agudo (shoshin-beriberi). / [Acute cardiovascular beriberi (shoshin-beriberi)]

Beriberi (BB), thiamine deficiency, has been described in the Asian literature in the 17th century and is characterized by peripheral neuropathy and muscle weakness, also called [quot ]dry[quot ] beriberi (BB) to differentiate it from [quot ]wet[quot ] BB, with essentially cardiovascular manifestations. Wet can be either [quot ]classic[quot ] wet BB in which signs and symptoms of right-sided heart failure with normal or high cardiac output are the presenting features or the [quot ]shoshin[quot ] BB variant with severe biventricular failure and metabolic acidosis, which must be treated early to prevent the rapid development of low cardiac output failure and sudden death. In this case, we report a 58 year old alcoholic woman who developed dyspnea, oliguria, edema, cardiac failure with high output, metabolic acidosis, renal tubular dysfunction and serum lactate level of 5.6 mEq/L. Neurological examination revealed peripheral neuropathy in the lower legs and cognitive alteration. She was treated with a loading dose of 100 mg of intravenous thyamine and responded with a marked increase in urine output, correction of acidosis, reduction in pulmonary-capillary wedge pressure and a change of the hemodynamic pattern. We conclude that shoshin-BB is uncommonly encountered but not widely recognized. In lactic acidosis and/or hyperdynamic circulation without any other apparent etiology in patients with possible vitamin B1 deficiency, the diagnosis of BB must be considered and thiamine should be administered.