Establishing an autogenous vascular access program in a Guatemalan comprehensive pediatric nephrology center.

BACKGROUND: The Guatemalan Foundation for Children with Kidney Diseases collaborated with Bridge of Life, a not-for-profit charitable organization, to establish a vascular access program. We reviewed our experience with graded surgical responsibility and structured didactic training, creating arteriovenous fistulas (AVF) for Guatemalan children. METHODS: Pediatric vascular access missions were completed from 2015 to 2023 and analyzed retrospectively. Follow-up was completed by the Guatemalan pediatric surgeons, nephrologists, and nursing staff. AVF patency and patient survival were evaluated by Kaplan-Meier life-table analysis with univariate and multivariable association between patient demographic variables by Cox proportional hazards models. RESULTS: Among a total of 153 vascular access operations, there were 139 new patient procedures, forming the study group for this review. The mean age was 13.6 years, 42.6% were female, and the mean BMI was 17.3. Radial or ulnar artery-based direct AVFs were established in 100 patients (71.9%) and ten of the 25 transposition procedures. Brachial artery inflow was required in 29 direct AVFs (20.9%). Two patients underwent femoral vein transpositions. Access-related distal ischemia was not encountered. Seven of the AVF patients later required access banding for arm edema; all had previous dialysis catheters (mean = 9, range 4-12). Primary and cumulative patency rates were 84% and 86% at 12 months and 64% and 81% at 24 months, respectively. The median follow-up was 12 months. Overall patient survival was 84% and 67% at 12 and 24 months, respectively. There were no deaths related to AVF access. CONCLUSIONS: Safe and functional AVFs were established in a teaching environment within a Guatemalan comprehensive pediatric nephrology center.

Effects of higher dietary acid load: a narrative review with special emphasis in children.

Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.

Fermented pomegranate juice enriched with pomegranate seed oil ameliorates metabolic disorders associated with a high-fat diet in C57BL/6 mice.

This study investigated the health-functional properties of a lactic fermented pomegranate juice (FPJ) enriched with pomegranate seed oil (FPJO) by using the fruit-origin strain Lactiplantibacillus paraplantarum CRL 2051 (FPJO-CRL2051). For this aim, the in vitro human antiplatelet aggregation effect and antioxidant activities were determined in the fermented juices while in vivo studies using high-fat-diet (HFD) C57BL/6 mice fed with a high-fat diet or pomegranate fermented juices for 8 weeks were performed. A high anti-platelet aggregation activity for FPJO-CRL2051 was determined. The formulated juice was administered to C57BL/6 HFD mice over 8 weeks, which showed a significant decrease in triglycerides, LDL-C, and pro-inflammatory cytokines levels. The FPJO-CRL2051 administration was effective in ameliorating liver damage caused by HFD, reducing fat accumulation and oxidative biomarkers, and improving the liver fatty acid profile by incorporation of conjugated fatty acids. This study shows the significance of lactic fermentation in developing novel fermented plant-based beverages with enhanced functional activities with a circular economy approach for the prevention of metabolic disorders.

Jabuticaba (Myrciaria trunciflora) extract improves metabolic and behavioral markers of obese rats fed on a hypercaloric diet.

BACKGROUND: Obesity is a metabolic disease that affects many individuals around the world, related to imbalance between energy consumption and expenditure, which can lead to comorbidities. A healthy diet can significantly contribute to the prevention or treatment of this condition. Jabuticaba is an emerging fruit presenting a wide range of bioactive compounds and is being extensively studied due to its effects on lipid metabolism. The aim of this study was to evaluate the jabuticaba extract in the anxious-like behavior and in the lipid and oxidative metabolism in the context of obesity. METHODS: Forty male Wistar rats divided into five groups were used. The animals received a standard diet and/or a hypercaloric diet and after 60 days of induction, interventions were carried out with jabuticaba extract (5% and 10%) via gavage for 30 days. RESULTS: It can be observed that the jabuticaba extract was able to reverse the anxious behavior observed in obese animals and modulate parameters of lipid and oxidative metabolism. We observed a reduction in cholesterol and triglyceride levels compared to obese animals. Furthermore, we observed an improvement in oxidative parameters, with a reduction in protein carbonylation in the liver and modulation of antioxidant enzymes such as superoxide dismutase and catalase. Contrary to expectations, we did not observe changes in leptin, adiponectin and tumor necrosis factor alpha (TNF-α) levels. CONCLUSION: Our work demonstrates that jabuticaba extract can improve metabolic, oxidative and behavioral changes in animals with obesity. © 2024 Society of Chemical Industry.

Bone age and dental late effects in childhood cancer survivors: Radiographic findings in a Brazilian sample.

BACKGROUND: Changes in bone age and tooth development are late side effects of cancer therapy and can be identified by imaging examination. AIM: To evaluate the late effects of antineoplastic treatment on bone age and dental development in childhood cancer survivors. DESIGN: This is a retrospective case-control study on paediatric cancer survivors of both sexes who underwent antineoplastic treatment with 5-15 years of survival. Carpal radiographs were assessed for bone age and growth curve, and panoramic radiographs were used to evaluate dental development and alterations. Carpal radiographs were analyzed using the Greulich and Pyle inspection method, and the Martins and Sakima method was used to analyze the growth curve. All tests were applied with a confidence level of 95%. RESULTS: The study and control groups comprised 28 and 56 patients, respectively. There was no significant difference in bone age and growth curve between the study and control groups. Nonetheless, when sex was compared to chronological and bone ages, there was a significant difference in bone age (p = 0.019) and an underestimation in both groups and sexes in the Greulich and Pyle method. As to late dental effects, dental agenesia, microdontia, gyroversion, and unerupted teeth were found. Dental shape alterations mainly involve the root region. CONCLUSION: Close multidisciplinary collaboration is necessary during the follow-up period of young patients who have survived cancer.

In Utero and Lactational Exposure to an Environmentally Relevant Mixture of Phthalates Alters Hypothalamic Gene Expression and Sexual Preference in Rats.

Several phthalates, mainly used as plasticizers, are known for their adverse effects on the male genital system. Previously, we demonstrated that an environmentally relevant mixture of six antiandrogenic phthalates (PMix), derived from a biomonitoring study in pregnant Brazilian women, was able to disrupt the reproductive development in male rats. Experimental groups (control, 0.1, 0.5, and 500 mg PMix/kg/day) were established starting from the extrapolated human dose (0.1 mg/kg/day), followed by doses 5 times and 5000 times higher. Pregnant rats received daily oral gavage administration of either vehicle (control) or PMix from gestational day 13 to postnatal day 10. Here, we examined male and female offspring regarding changes in gene expression of key reproductive factors in the hypothalamus and pituitary gland at adulthood and conducted a battery of behavioral tests in males, including partner preference, sexual behavior, and male attractiveness tests. PMix induced some changes in mating-related behavior in males, as demonstrated by the absence of preference for females against males and a higher number of penetrations up to ejaculation in the 0.5 dose group. PMix decreased Esr2 expression in the male hypothalamus across all three doses, and in females at mid and high doses in both the hypothalamus and pituitary. In male hypothalamus, we also observed decreased Kiss1 transcripts in these groups and a reduction in AR at the 0.5 dose group. In summary, our results provide further evidence that phthalates in a mixture, even at low doses, may exert cumulative effects on the structures underlying sexual behavior, which seems to be more sensitive than reproductive endpoints for the same experimental design.

Astaxanthin improves lipotoxicity, lipid peroxidation and oxidative stress in kidney of sucrose-rich diet-fed rats.

Metabolic Syndrome (MS) is a cluster of metabolic risk factors, characterized by abdominal obesity, dyslipidemia, hypertension, insulin resistance, among others. The purpose of the study was to evaluate the astaxanthin (AXT) effects extracted from freshwater crab (Dilocarcinus pagei) at the Paraná Basin on lipotoxicity, lipid peroxidation and oxidative stress in the kidney of rats fed with a sucrose-rich diet (SRD). We hypothesized that daily administration of AXT prevents kidney damage by reducing lipotoxicity, lipid peroxidation, and reactive oxygen species (ROS), and by improving antioxidant enzyme defenses and crosstalk between NrF2 and NF-ĸB transcription factors. Male Wistar rats were fed a reference diet (RD), RD+AXT, SRD and SRD+AXT (AXT daily oral dose: [10 mg/kg body weight]) for 90 days. Systolic and diastolic blood pressure, biochemical assays in serum and urine were evaluated. Renal cortex samples were taken for histological analysis, determination of triglyceride content, ROS, thiobarbituric acid reactive substances (TBARS), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) enzyme activities and glutathione content (GSH). 4-HNE, NrF2, and NF-ĸB p65 expression were analyzed by immunohistochemistry. We demonstrated that daily oral supplementation of AXT to animals fed a SRD reduced systolic and diastolic blood pressure, histological renal damage, lipid accumulation, ROS and lipid peroxidation, and increased CAT and GPx activities. NrF2 protein expression in renal cortex was increased, whilst NF-ĸB p65 was reduced. AXT extracted from freshwater crabs (Dilocarcinus pagei) may be promising nutritional strategy for the prevention of renal alterations present in this model.

Distal versus traditional radial access in patients undergoing emergency coronary angiography or percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Distal radial access (DRA) is a well-tolerated and effective alternative to traditional radial access (TRA) for coronary procedures. However, the comparative value of these modalities remains unknown in the emergency setting, particularly in patients with ST-elevation myocardial infarction (STEMI). OBJECTIVE: To compare DRA versus TRA for emergency coronary procedures through a meta-analysis. METHODS: We systematically searched PubMed , Embase , and Cochrane databases to identify studies comparing DRA versus TRA in patients undergoing emergency coronary angiography (CAG) or percutaneous coronary intervention (PCI). All statistical analyses were performed using R software version 4.3.1 with a random-effects model. RESULTS: We included four studies comprising 543 patients undergoing emergency CAG or PCI, of whom 447 (82.3%) had STEMI. As compared with TRA, DRA was associated with lower radial artery occlusion rates (RR, 0.21; 95% CI, 0.06-0.72) and shorter hemostasis time (MD, -4.23 h; 95% CI, -6.23 to 2.13). There was no significant difference between modalities in terms of puncture failure (RR, 1.38; 95% CI, 0.31-6.19), crossover access (RR, 1.37; 95% CI, 0.42-4.44), puncture time (SMD, 0.33; 95% CI, -0.16 to 0.81), procedure time (MD, 0.97 min; 95% CI, -5.19 to 7.13), or rates of cannulation success (RR, 0.94; 95% CI, 0.83-1.06). In terms of other periprocedural complications, there were no differences between both groups. These findings remained consistent in a subgroup analysis of patients with STEMI. CONCLUSION: In this meta-analysis, DRA was superior to TRA in terms of radial artery occlusion and hemostasis time, with similar rates of periprocedural complications.

Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.

BACKGROUND: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited. AIM: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT. METHODS: A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of de novo DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex® single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy. RESULTS: Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively. CONCLUSION: Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Bedaquiline versus injectable containing regimens for rifampicin-resistant and multidrug-resistant tuberculosis in a reference center in Brazil - a real-world evidence study using a retrospective design.

BACKGROUND: Drug resistance (DR) is one of the several challenges to global tuberculosis (TB) control. The implementation of bedaquiline (BED) for DR-TB after more than 40 years was expected to improve treatment outcomes as well as microbiologic conversion and adverse events (AE) occurrence. METHODS: Retrospective cohort study based on secondary data of patients with rifampicin-resistant (RR) or multidrug-resistant (MDR) TB reported to the Outpatient Clinic of Mycobacterial Diseases of the Thorax Diseases Institute - Federal University of Rio de Janeiro - Brazil, between 2016 and 2023. We aimed to evaluate microbiologic conversion, AE and TB treatment outcomes and compare them according to the treatment regimen used for RR/MDR-TB patients under routine conditions [Injectable Containing Regimens (ICR) versus BED Containing Regimens (BCR)]. Logistic regression and survival analysis using Cox regression and Kaplan Meier curve were used for statistical analysis. RESULTS: Of the 463 DR-TB patients notified during the study period, 297 (64.1%) were included for analysis (ICR = 197 and BCR = 100). Overall AEs were more frequent (83.7 vs. 16.3%, p < 0.001) and occurred earlier in the ICR group (15 days vs. 65 days, p = 0.003). There were no cases of cardiotoxicity requiring interruption of BED treatment. None of the regimens of treatment tested were associated with smear or culture conversion on Cox regression analysis (p = 0.60 and 0.88, respectively). BED-containing regimens were also associated with favorable outcomes in multivariable logistic regression [adjusted odds ratio (aOR) = 2.63, 95% confidence interval (CI)1.36-5.07, p = 0.004], as higher years of schooling, primary drug resistance, and no previous TB treatment. In the survival analysis, BCR was inversely associated with the occurrence of AE during treatment follow-up (aHR 0.24, 95% CI 0.14-0.41, p < 0.001). In addition, TB treatment regimens with BED were also associated with favorable outcomes (aHR 2.41, 95% CI 1.62-3.57, p < 0.001), along with no illicit drug use and primary drug resistance. CONCLUSIONS: The implementation of a fully oral treatment for RR/MDR-TB in a reference center in Brazil was safe and associated with favorable outcomes under routine conditions, despite social, demographic, and behavioral factors that may influence TB treatment completion.

[Exanthema after dengue vaccine (TAK003): first data of passive surveillance in a private vaccination center in Argentina]. / Exantema luego de la aplicación de la vacuna para dengue (TAK003): primeros datos de vigilancia pasiva en un centro de vacunación privado de Argentina.

INTRODUCTION: The tetravalent live virus vaccine developed by Takeda called Qdenga® is available in Argentina and approved for use from 4 years of age without age limit. The objective was to describe clinical characteristics and evolution of the initial reports of rash after the first dose. MATERIAL AND METHODS: The records of Events Supposedly Attributable to Vaccination or Immunization Reported in a Private Vaccination Center were reviewed between 15/11/2023 and 12/12/2023. Cases with skin rash that occurred outside the application site area were included. The main variables analyzed were age, sex, history of dengue, characteristics of the skin rash, accompanying symptoms, time elapsed from vaccination to the onset of the rash and evolution. The incidence of rash was calculated: cases/10,000 vaccinated. RESULTS: Out of 12 551 doses applied, 15 cases were included. Median age: 35 years, female sex: 8/15. Clinical forms of presentation: generalized micropapular (3/15), maculopapular (3/15), scarlatiniform (1/15), urticarian (1/15), multiform (1/15), erythematous in the face (1/15) and unspecified (5/15). Most common concomitant symptoms: pruritus (5/15), fever or low-grade fever (6/15), headache (3/15), retro-ocular pain (2/15), asthenia (2/15). Three cases reported a history of dengue. The median number of days of rash presentation was 8 days' postvaccination. All patients progressed favorably. The overall incidence was 1.2/1000 vaccinated. CONCLUSIONS: In passive surveillance, after more than 12 000 first doses administered, the presence of rash was observed in less than 0.12% of those vaccinated. Everyone evolved favorably.

Introducción: La vacuna tetravalente a virus vivos del laboratorio Takeda, denominada Qdenga®, está disponible en Argentina y aprobada para su uso a partir de los 4 años sin límite de edad. El objetivo fue describir las características clínicas y evolución de los primeros reportes de exantema post primera dosis. Material y métodos: Se revisaron los registros de los Eventos Supuestamente Atribuidos a la Vacunación e Inmunización reportados en los Centros Vacunar entre el 15/11/2023 al 12/12/2023. Se incluyeron los casos con exantema cutáneo que se presentaron fuera del área del sitio de aplicación. Las principales variables analizadas fueron edad, sexo, antecedente de dengue, características del exantema cutáneo, síntomas acompañantes, tiempo transcurrido desde la vacunación al inicio del exantema y evolución. Se calculó la incidencia del exantema: casos/1000 vacunados. Resultados: Sobre 12551 dosis aplicadas se incluyeron 15 casos. Mediana de edad: 35 años, sexo femenino: 8/15. Formas clínicas de presentación: generalizado micropapular (3/15), maculopapular (3/15), escarlatiniforme (1/15), urticariano (1/15), multiforme (1/15), eritematoso en cara (1/15) y sin especificar (5/15). Síntomas concomitantes más frecuentes: prurito (5/15), fiebre o febrícula (6/15), cefalea (3/15), dolor retro ocular (2/15), astenia (2/15). Tres casos refirieron antecedente de dengue. La mediana de días de presentación del exantema fue de 8 días post vacunación. Todos los pacientes evolucionaron favorablemente. La incidencia fue de 1.2/1000 vacunados. Conclusiones: En la vigilancia pasiva, luego de más de 12 000 primeras dosis administradas, se observó la presencia de exantema en menos del 0.12% de los vacunados. Todos evolucionaron favorablemente.

[Disorders in plasmatic levels of potassium, magnesium, and calcium in elderly adults associated with colistin: time series]. / Trastornos en niveles plasmáticos de potasio, magnesio y calcio en adultos mayores asociados a colistina: serie de tiempo.

INTRODUCTION: Water and electrolyte disturbances associated with colistin are understudied adverse effects in the medical literature. We aim to evaluate their incidence in hospitalized older adult patients. MATERIALS AND METHODS: A longitudinal retrospective study of the interrupted time series type was conducted on patients admitted to Dr. César Milstein Hospital. We included adults aged 65 and older who received colistin with normal serum potassium, magnesium, and calcium at the outset. Electrolyte values were collected before, during and after suspending the antibiotic. Values were compared using non-parametric tests, and a multivariate linear regression model with robust intervals was performed to assess sociodemographic and clinical characteristics associated with serum concentrations. RESULTS: A total of 89 patients were included. The rate of hypokalemia was 77.5% (n=69), and factors associated with potassium decline included older age, increased creatinine levels, and longer colistin treatment duration. Serum magnesium disturbances were reported in 66 (79.5%) of the 83 patients evaluated. The decrease in both electrolytes was statistically significant in the measured times and both values normalized after 72 hours of stopping antibiotic therapy. The incidence of acute kidney injury during colistin treatment in patients with normal baseline creatinine was 63.6% (n = 42/66), and in those with abnormal baseline creatinine, it was 47.8% (n = 11/23). CONCLUSION: We report high rates of electrolyte disturbances in patients treated with colistin, with hypokalemia being the most frequent, showing resolution following discontinuation of antibiotic therapy. Continuous monitoring of electrolyte levels and renal function during colistin treatment is crucial.

Introducción: Los trastornos hidroelectrolíticos asociados a la colistina son efectos adversos poco estudiados en la literatura médica. Nos propusimos evaluar su incidencia en pacientes adultos mayores hospitalizados. Materiales y métodos: Se realizó un estudio longitudinal retrospectivo, del tipo serie de tiempo interrumpida, en pacientes internados mayores de 65 años que recibieron colistina, con potasio, magnesio y calcio séricos normales al inicio. Se recabaron valores de dichos electrolitos previo, durante y luego de suspender el antibiótico. Se compararon los valores mediante test no paramétricos y se realizó un modelo multivariado de regresión lineal con intervalos robustos para evaluar las características sociodemográficas y clínicas asociadas a las concentraciones séricas. Resultados: Se incluyeron 89 pacientes. La tasa de hipocalemia fue del 77.5% (n = 69) y las variables asociadas al descenso del potasio fueron mayor edad, aumento de creatininemia, y duración de tratamiento con colistina. Se informaron trastornos del magnesio en 66 (79.5%) de los 83 pacientes evaluados. El descenso de ambos electrolitos fue estadísticamente significativo en los tiempos medidos, y ambos normalizaron valores tras 72 horas de suspendida la antibioticoterapia. La incidencia de insuficiencia renal aguda en pacientes con creatinina basal normal fue del 63.6%, (42/66) y con creatinina basal anormal de 47.8% (11/23). Conclusión: En pacientes tratados con colistina, el trastorno más frecuente fue la hipocalemia, mostrando resolución tras la suspensión del antibiótico. Es importante la monitorización constante de los niveles de electrolitos y la función renal durante el tratamiento con colistina.

[Reevaluation of penicillin allergy labeling, appropriate use of ß-lactam antibiotics, and multidrug resistance]. / Reevaluación del rótulo de alergia a penicilina, el uso adecuado de antibióticos ß-lactámicos y la multirresistencia.

Approximately 10% of the population reports being allergic to penicillin, although usually less than 1% really are. In addition, people with proven allergies over the years may no longer be allergic. Unconfirmed penicillin allergy and use of alternative antimicrobials result in more treatment failures; more severe adverse effects. Higher cost; longer hospitalizations; increase in the emergence of multi-resistant germs associated with health care. The risk of cross-allergy between ß-lactam groups is usually <2%, depending on the similarity of the side chains, so prescribing antibiotics from another ß-lactam group is safe as long as we take into account the structural similarity. Incorporating the reassessment of allergies and improving the prescription of antibiotics in this group of patients reduces the generation and spread of multi-resistant germs, and the associated costs. There are simple methods and specific scores that simplify allergy reassessment. The objective of this review is to expose how, through these methods, the delabeling of patients erroneously labeled as allergic and the safe prescription of ß-lactam antibiotics can be achieved.

Aproximadamente el 10% de la población refiere ser alérgico a la penicilina, aunque habitualmente menos del 1% lo es; además las personas con alergia demostrada con el paso de los años pueden dejar de ser alérgicos. La alergia a la penicilina sin confirmación y el uso de antimicrobianos alternativos tienen como efecto más fallas en el tratamiento; más efectos adversos graves; mayor costo; internaciones más prolongadas; incremento en la emergencia de gérmenes multirresistentes asociados a los cuidados de la salud. El riesgo de alergia cruzada entre grupos de ß-lactámicos suele ser <2%, dependiendo de la similitud de las cadenas laterales, por lo que prescribir antibióticos de otro grupo de ß-lactámicos es seguro siempre que tengamos en cuenta la similitud estructural. Incorporar la reevaluación de alergias y mejorar la prescripción de antibióticos en este grupo de pacientes, disminuye la generación y propagación de gérmenes multirresistentes, y los costos asociados. Existen métodos sencillos y escalas específicas que permiten simplificar la reevaluación de la alergia. El objetivo de esta revisión es exponer cómo a través de estos métodos, puede lograrse el desrotulado de pacientes erróneamente etiquetados como alérgicos y la prescripción segura de antibióticos ß-lactámicos.

Linoleic Acid Induces Metabolic Reprogramming and Inhibits Oxidative and Inflammatory Effects in Keratinocytes Exposed to UVB Radiation.

Linoleic acid (LA), the primary ω-6 polyunsaturated fatty acid (PUFA) found in the epidermis, plays a crucial role in preserving the integrity of the skin's water permeability barrier. Additionally, vegetable oils rich in LA have been shown to notably mitigate ultraviolet (UV) radiation-induced effects, including the production of reactive oxygen species (ROS), cellular damage, and skin photoaging. These beneficial effects are primarily ascribed to the LA in these oils. Nonetheless, the precise mechanisms through which LA confers protection against damage induced by exposure to UVB radiation remain unclear. This study aimed to examine whether LA can restore redox and metabolic equilibria and to assess its influence on the inflammatory response triggered by UVB radiation in keratinocytes. Flow cytometry analysis unveiled the capacity of LA to diminish UVB-induced ROS levels in HaCaT cells. GC/MS-based metabolomics highlighted significant metabolic changes, especially in carbohydrate, amino acid, and glutathione (GSH) metabolism, with LA restoring depleted GSH levels post-UVB exposure. LA also upregulated PI3K/Akt-dependent GCLC and GSS expression while downregulating COX-2 expression. These results suggest that LA induces metabolic reprogramming, protecting against UVB-induced oxidative damage by enhancing GSH biosynthesis via PI3K/Akt signaling. Moreover, it suppresses UVB-induced COX-2 expression in HaCaT cells, making LA treatment a promising strategy against UVB-induced oxidative and inflammatory damage.

Reconstruction of bone defects around the ankle with retrograde gentamicin-coated tibial intramedullary nail (ETN PROtect™) for tibiotalocalcaneal arthrodesis: a case series.

PURPOSE: The objective of this study was to describe the use of retrograde gentamicin-coated tibial intramedullary nail (ETN PROtect™) in patients with tibial defects who required a tibiotalocalcaneal arthrodesis (TTC). METHODS: Consecutive series case review of seven men treated with TTC using retrograde PROtect™ between January 2018 and December 2023. The main outcomes evaluated were fracture union, complications, and the health-related quality of life using the EuroQol five-dimension three-level questionnaire (EQ-5D-3L). RESULTS: The mean age was 45.3 ± 8.0 years. Six patients had a clinical history of chronic osteomyelitis, and one case underwent TTC for congenital pseudoarthrosis. Fracture union was achieved in 5 of 7 patients between 4 and 11 months after surgery. Three patients developed complications; two patients had fistulas, and one had persistent pain. At the end of the follow-up, a median of 70 points (interquartile range: 60 to 90) on the EQ-5D-3L was reported. No complications directly attributed to the use of the PROtect™ were reported. CONCLUSION: TTC with retrograde PROtect™ is a prophylactic treatment option in patients with tibial defects treated with external fixation requiring a tibiotalar and subtalar arthrodesis. This novel use of PROtect™ allows simultaneous fixation of the tibiotalocalcaneal joint and protection of the regenerated bone, facilitating earlier rehabilitation in patients at high risk for postoperative infections.

Pharmacogenetics of DPYD and treatment-related mortality on fluoropyrimidine chemotherapy for cancer patients: a meta-analysis and trial sequential analysis.

BACKGROUND: Fluoropyrimidines are chemotherapy drugs utilized to treat a variety of solid tumors. These drugs predominantly rely on the enzyme dihydropyrimidine dehydrogenase (DPD), which is encoded by the DPYD gene, for their metabolism. Genetic mutations affecting this gene can cause DPYD deficiency, disrupting pyrimidine metabolism and increasing the risk of toxicity in cancer patients treated with 5-fluorouracil. The severity and type of toxic reactions are influenced by genetic and demographic factors and, in certain instances, can result in patient mortality. Among the more than 50 identified variants of DPYD, only a subset has clinical significance, leading to the production of enzymes that are either non-functional or impaired. The study aims to examine treatment-related mortality in cancer patients undergoing fluoropyrimidine chemotherapy, comparing those with and without DPD deficiency. METHODS: The meta-analysis selected and evaluated 9685 studies from Pubmed, Cochrane, Embase and Web of Science databases. Only studies examining the main DPYD variants (DPYD*2A, DPYD p.D949V, DPYD*13 and DPYD HapB3) were included. Statistical Analysis was performed using R, version 4.2.3. Data were examined using the Mantel-Haenszel method and 95% CIs. Heterogeneity was assessed with I2 statistics. RESULTS: There were 36 prospective and retrospective studies included, accounting for 16,005 patients. Most studies assessed colorectal cancer, representing 86.49% of patients. Other gastrointestinal cancers were evaluated by 11 studies, breast cancer by nine studies and head and neck cancers by five studies. Four DPYD variants were identified as predictors of severe fluoropyrimidines toxicity in literature review: DPYD*2A (rs3918290), DPYD p.D949V (rs67376798), DPYD*13 (rs55886062) and DPYD Hap23 (rs56038477). All 36 studies assessed the DPYD*2A variant, while 20 assessed DPYD p.D949V, 7 assessed DPYD*13, and 9 assessed DPYDHap23. Among the 587 patients who tested positive for at least one DPYD variant, 13 died from fluoropyrimidine toxicity. Conversely, in the non-carrier group there were 14 treatment-related deaths. Carriers of DPYD variants was found to be significantly correlated with treatment-related mortality (OR = 34.86, 95% CI 13.96-87.05; p < 0.05). CONCLUSIONS: This study improves our comprehension of how the DPYD gene impacts cancer patients receiving fluoropyrimidine chemotherapy. Identifying mutations associated with dihydropyrimidine dehydrogenase deficiency may help predict the likelihood of serious side effects and fatalities. This knowledge can be applied to adjust medication doses before starting treatment, thus reducing the occurrence of these critical outcomes.

Air pollution exposure during pregnancy and preterm birth in Brazil.

Ambient air pollution is a significant environmental risk factor for adverse pregnancy outcomes, including preterm birth. However, the impact of different pollutants across various regions and trimesters of pregnancy has not been fully investigated in Brazil. This study aimed to examine the associations between exposure to PM2.5, NO2, and O3 during different trimesters of pregnancy and the risk of preterm birth across five regions of Brazil. We used logistic regression models to estimate the odds ratios (OR) of preterm birth associated with PM2.5, NO2, and O3 adjusting for potential confounders such as maternal age, education, and socioeconomic status. Our study included over 9.9 million live births from 2001 to 2018, with data obtained from the Ministry of Health in Brazil. On average, for each 1-µg/m3 increase in PM2.5, we estimated a 0.26 % (95 % CI: 0.08-0.44 %) increase in the risk of preterm birth nationally in the first trimester. For NO2, each 1ppb increase was associated with a percentage increase in preterm birth risk of 7.26 % (95 % CI: 4.77-9.74 %) in the first trimester, 8.05 % (95 % CI: 5.73-10.38 %) in the second trimester, and 7.48 % (95 % CI: 5.25-9.72 %) in the third trimester. For O3, each 1ppb increase was associated with a percentage increase in preterm birth risk of 1.24 % (95 % CI: 0.29-2.18 %) in the first trimester, 1.51 % (95 % CI: 0.60-2.41 %) in the second trimester, and 0.72 % (95 % CI: -0.18-1.62 %) in the third trimester. This study highlights the significant impact of ambient air pollution on preterm birth risk in Brazil, with significant regional variations. Our findings underscore the need for targeted public health interventions to mitigate the effects of air pollution on pregnancy outcomes, particularly in the most affected regions.

Intriguing hepatoprotective effects of sucrose on hepatocellular carcinoma pathogenesis.

Chronic liver disease is closely linked to dietary intake factors, such as high consumption of simple carbohydrates including sucrose. In this study, the influence of sucrose on the development of hepatocellular carcinoma (HCC), the most common primary liver malignancy, was explored. Using the hepatocarcinogen diethylnitrosamine (DEN) to induce HCC in the rat, we co-administered sucrose with DEN. The co-administration significantly modified body, liver and pancreas weight, as well as, serum fatty acids and triglycerides. DEN caused liver structural alteration, fibrosis, and tumor formation; surprisingly, co-administration with sucrose restored hepatic lipids, improved liver architecture, and reduced fibrosis and tumor development. Sucrose intake negatively regulated tumor markers and cell proliferation, and reduced the expression of genes associated with lipid metabolism and oxidative stress response. These findings highlight a hepatoprotective effect of sucrose during DEN-induced hepatocarcinogenesis, underlining an intriguing role of high sucrose consumption during HCC development and providing new insights as well as possible pathways of cellular protection under sucrose intake on hepatocarcinogenesis.

Gastrointestinal symptoms in patients using methotrexate: A cross-sectional study in a sample with rheumatoid arthritis.

BACKGROUND: Gastrointestinal intolerance is common in rheumatoid arthritis (RA) patients using methotrexate and may lead to treatment discontinuation. AIM: To study the prevalence of gastrointestinal symptoms in a sample of RA methotrexate users as well as its possible association with clinical and epidemiological variables. METHODS: Cross-sectional study of 192 patients with gastrointestinal symptoms using the MISS (methotrexate intolerance severity score). Clinical and epidemiological variables were collected through chart review and direct questioning. Patients' adherence to methotrexate was evaluated through Moriski-Green-Levin questionnaire. RESULTS: The prevalence of gastrointestinal complaints was high with 55.7% of the sample classified as intolerant. Nausea and pain after drug ingestion were the most common reported complaints. This intolerance was associated with afro-descendant background (p=0.02); presence of associated fibromyalgia (p=0.04), concomitant use of glucocorticoids (p=0.03) and Jak inhibitors (0.03). A tendency towards association with leflunomide use was observed (p=0.06). Logistic regression was used to test drug associations with methotrexate intolerance, and showed that glucocorticoid use was independently associated with methotrexate intolerance OR=1.85; 95% CI=1.01-3.44; p=0.04. Route of administration, presence of previous gastric complaints, age and methotrexate dose did not interfere with MISS. MISS results were associated with moderate adherence to the drug. CONCLUSIONS: There is a high rate of methotrexate intolerance that is more common in afro-descendants, those with associated fibromyalgia, glucocorticoid and Jak inhibitors users.

[Heart failure due to arteriovenous fistula for hemodialysis. Presentation of two clinical cases]. / Insuficiencia cardíaca por fístula arteriovenosa para hemodiálisis. Presentación de dos casos clínicos.

Arteriovenous fistulas for hemodialysis create a leftto-right shunt, resulting in an average 25% increase in cardiac output and subsequent remodeling of cardiac chambers. Some of these patients may develop highoutput heart failure. In this report, we present two cases of heart failure associated with an arteriovenous fistula for hemodialysis, each showing distinct clinical outcomes following either its occlusion or cerclage. Drawing from existing medical literature, we explore potential causes that might account for the divergent clinical courses observed in these cases.

Las fístulas arteriovenosas para hemodiálisis generan un cortocircuito de izquierda a derecha con un incremento promedio en el gasto cardíaco del 25%, asociado a remodelado de las cavidades cardíacas. Un porcentaje de estos pacientes desarrollan insuficiencia cardíaca con alto gasto cardíaco. Presentamos dos casos de insuficiencia cardíaca asociada a fístula arteriovenosa para hemodiálisis, con diferente evolución clínica luego de la oclusión o cerclaje de la misma. Basados en la literatura médica, se discuten las potenciales causas que pudieron justificar las diferencias en la evolución clínica entre ambos casos.