Allostasis, health, and development in Latin America.

The lifespan is influenced by adverse childhood experiences that create predispositions to poor health outcomes. Here we propose an allostatic framework of childhood experiences and their impact on health across the lifespan, focusing on Latin American and Caribbean countries. This region is marked by significant social and health inequalities nested in environmental and social stressors, such as exposure to pollution, violence, and nutritional deficiencies, which critically influence current and later-life health outcomes. We review several manifestations across cognition, behavior, and the body, observed at the psychological (e.g., cognitive, socioemotional, and behavioral dysfunctions), brain (e.g., alteration of the development, structure, and function of the brain), and physiological levels (e.g., dysregulation of the body systems and damage to organs). To address the complexity of the interactions between environmental and health-related factors, we present an allostatic framework regarding the cumulative burden of environmental stressors on physiological systems (e.g., cardiovascular, metabolic, immune, and neuroendocrine) related to health across the life course. Lastly, we explore the relevance of this allostatic integrative approach in informing regional interventions and public policy recommendations. We also propose a research agenda, potentially providing detailed profiling and personalized care by assessing the social and environmental conditions. This framework could facilitate the delivery of evidence-based interventions and informed childhood-centered policy-making.

Tocilizumab demonstrates superiority in decreasing C-reactive protein levels in hospitalized COVID-19 patients, compared to standard care treatment alone.

Severe acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crisis. The virus triggers the activation of inflammatory reactants including interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP), causing multiorgan damage, particularly affecting the lungs. Tocilizumab, an IL-6 receptor blocker, has the potential to diminish the progression of the disease and reduce organ damage and long-term complications. The aim of this observational retrospective cohort study was to evaluate the efficacy of tocilizumab in decreasing CRP levels in hospitalized coronavirus disease 2019 (COVID-19) patients compared to standard care without the drug. The study included 141 patients during their Hospital Stay (HS), with 100 in the Tocilizumab group and 41 in the non-Tocilizumab group. Clinical information was collected from the electronic clinical record, analyzed using statistical software, and homogenized the CRP levels from the severe group to the levels of the less complicated group at 48 h of hospitalization. The results showed a statistically significant greater decrease in CRP levels in the Tocilizumab group at 48 h after the use of the treatment, with no differences in mortality or length of stay between the groups. In conclusion, tocilizumab accelerates the diminishing of CRP levels compared to standard treatment alone, and its use may have potential benefits in the management of severe COVID-19 patients when used alongside with follow-up quantification of CRP levels reduction.IMPORTANCESevere acute respiratory syndrome coronavirus 2 has caused a global pandemic, leading to health, economic, and political crises. International guidelines for managing coronavirus disease 2019 (COVID-19) give recommendations according to the severity of the disease and the level of oxygen therapy needed. Tocilizumab is an option for the therapeutic management of hospitalized patients with any level of oxygen therapy; IL-6 serum level is the parameter for the follow-up on the efficacy, but it is not available at many hospitals. In this study, we demonstrate that C-reactive protein determination can predict the response to tocilizumab in severe COVID-19, the target patients for treatment with this drug. The use of this affordable and extensively available biomarker supports clinical decisions for the early escalation of the therapy and for the rational use of this drug on those prone to improve with the use of it.

Searching for the Culprit: Metastases from a Cancer of Unknown Primary.

We report a case of metastases from a cancer of unknown primary whose primary site could not be identified during the appropriate pretreatment evaluation. The patient was a 58-year-old woman with a history of passive smoking and with no history of cancer in the family. Her current condition started with asthenia, adynamia, and pallor, followed by palpitations. An abdominopelvic computed tomography (CT) scan was performed, showing multiple osteolytic lesions distributed in all bone structures and axillary adenopathy on the left side. As part of the approach and given the high suspicion of multiple myeloma, tests were performed. The results were negative for multiple myeloma. A PET-CT scan was performed and showed left axillary adenopathy. The breasts and other organs were not affected. Left axillary lymph node resection revealed breast primary metastatic pleomorphic lobular carcinoma. Due to the metastatic disease (caused by the primary breast cancer), it was decided to start chemotherapy.

Utilidad clínica de la medición de la hormona antimülleriana en niños / Clinical utility of anti-mullerian hormone measurement in children

Resumen: la hormona antimülleriana, inicialmente denominada sustancia inhibitoria mülleriana, es una glicoproteína homodimérica de 12,5 kDa, que pertenece a la familia del factor de crecimiento transformante beta (TGF-ß) y desempeña un papel crucial en la diferenciación sexual masculina al favorecer la regresión de los conductos de Müller. Dado que su producción en el varón es principalmente por las células de Sertoli inmaduras, en las últimas décadas ha crecido su utilidad más allá de la evaluación de la función ovárica y tratamientos de fertilidad en las mujeres, lo que ha permitido evaluar en el varón la función testicular y los estados de hipogonadismo, trastornos de la diferenciación sexual, pubertad patológica, criptorquidia, entre otras condiciones clínicas revisadas en este manuscrito. Además, esta revisión describe el rol fisiológico de la hormona antimülleriana en los testículos prepuberales y las pruebas de laboratorio disponibles para su medición. (AU)

Abstract: The antimullerian hormone, initially referred as mullerian inhibitory substance, is a 12.5 kDa homodimeric glycoprotein, belonging to the transforming growth factor beta (TGF-ß) family that playing a crucial role in male sexual differentiation by favoring regression of the Mullerian ducts. Since their production in the male is mainly by the immature Sertoli cells, in the last decades its usefulness has growth beyond the evaluation of the ovarian function and female fertility treatments, which has allowed evaluating the testicular function in male and affections such as hypogonadism, disorders of sexual differentiation, pathological puberty, cryptorchidism and others clinical conditions reviewed in this manuscript. In addition, this review describes the physiological role of the antimüllerian hormone in the prepubertal testes and the laboratory tests available for its measurement. (AU)

Utilidad clínica de la medición de la hormona antimülleriana en las mujeres / Clinical utility of the measurement of the Anti-müllerian hormone in women

Resumen: la hormona antimülleriana es una glicoproteína homodimérica perteneciente a la superfamilia del factor de crecimiento transformantes beta (TGF-ß). Esta hormona desempeña un papel fundamental en la regresión de los conductos müllerianos en el embrión masculino. En los niños se produce en los testículos, por las células de Sertoli, hasta la pubertad y a partir de allí disminuye lentamente a valores residuales por el resto de la vida. En las mujeres la hormona antimülleriana es secretada por las células de la granulosa de pequeños folículos en el ovario, donde sus niveles reflejan con exactitud la reserva folicular ovárica. Por tal motivo, esta hormona es considerada un marcador extremadamente sensible del envejecimiento ovárico y una herramienta valiosa en el diagnóstico y el reconocimiento de la recurrencia de tumores de células de la granulosa. La evaluación de la hormona antimülleriana también es de importancia clínica en la predicción de la respuesta ovárica, el cese de la función ovárica y la reproducción asistida. Además, puede servir como marcador diagnóstico del síndrome de ovario poliquístico, en los casos en que el examen ultrasonográfico no sea posible de realizar. Finalmente, la medición de los niveles séricos de la hormona antimülleriana, durante la vida reproductiva de la mujer, representa una herramienta ideal para la evaluación de la reserva folicular ovárica. En esta revisión se presenta el rol fisiológico de la hormona antimülleriana en las mujeres, al igual que las principales utilidades clínicas de su medición y las pruebas de laboratorio disponibles para este fin. (AU)

Abstract: Anti-mullerian hormone is a homodimeric glycoprotein belonging to the transforming growth factor beta (TGF-ß) super family. Anti-mullerian hormone plays a fundamental role in the regression of mullerian ducts in male embryo. In boys, it is produced by Sertoli cells of the testes until puberty where slowly decreases to residual values for the rest of the life. In female, it is secreted by granulosa cells of small follicles in the ovary where their levels accurately reflect the ovarian follicular reserve. Therefore, anti-mullerian hormone has been considered as extremely sensitive marker of ovarian aging and a valuable tool in the diagnosis and the recognition of recurrence of granulosa cell tumor. Anti-mullerian hormone evaluation is also of clinical importance in predicting of ovarian responsiveness, ovarian function cessation, and in assisted reproduction. In addition, anti-mullerian hormone could be a diagnostic marker of polycystic ovary syndrome in cases in which ultrasonographic examination is not possible. Finally, the measurement of serum anti-mullerian hormone levels during woman's reproductive life represents an ideal tool for the assessment of the ovarian follicular reserve. This review presents the physiological role of anti-mullerian hormone in women, as well as the main clinical benefits of its measurement and the laboratory tests available for this purpose. (AU)

Uso de clorhexidina y su papel preventivo en las infecciones del torrente sanguíneo asociadas a catéteres en los recién nacidos: revisión de tema / Use of chlorhexidine and its preventive role in catheter-associated bloodstream infections in newborns: a review

Resumen: las infecciones asociadas al cuidado de la salud representan un problema de salud pública y son un indicador de la calidad en prestación y gestión en salud. Es por esto que ha sido necesaria la creación de programas de vigilancia y control epidemiológico, y la adaptación e implementación de guías para su prevención. Estas estrategias mejoran la seguridad del pacientey deben ser una prioridad para las instituciones. En este contexto, la infección asociada a catéter es la más común de las infecciones asociadas al cuidado de la salud, principalmente en la población pediátrica, siendo los neonatos los más susceptibles a causa de la inmadurez de sus barreras primarias y sistema inmunológico, y a la alta frecuencia de procedimientos invasivos como los accesos vasculares para la administración de medicamentos o la nutrición parenteral. Actualmente existen múltiples medidas para prevenir dichas infecciones en pediatría y la tendenciaes crear estrategias bien estructuradas para facilitar su aplicación. La higiene de manos continúa siendo un pilar fundamental dentro de todos los protocolos para disminuir las tasas de infección asociadas al cuidado de la salud; sin embargo, se requiere de nuevas estrategias para la prevención de las mismas, como el uso de la clorhexidina como antiséptico tópico previo a la inserción de dispositivos intravasculares y el aseo rutinario en pacientes con caracteres centrales, lo cual es el objeto de revisión de este manuscrito.

Abstract: health care-associated infections are a public health concern and reflect healthcare quality. Hereby, it has been necessary to establish an epidemiologic surveillance system and the adaptation and implementation of guidelines for its prevention. These strategies improve safety in health care and must be a priority for all institutions. The most common healthcare-associated infection is catheter-associated bloodstream infection, especially in the pediatric population, with the newborns as the most vulnerable group due to immaturity of their immune system and the high rate of invasive procedures such as prolonged vascular access for administration of medicationor parenteral nutrition. Nowadays there are many proposals to prevent the infections in pediatricsand the current trend is to create well-structured strategies in order to facilitate their application. Hand’s hygiene remains a cornerstone in all the protocols to reduce the health care-associated infections, nevertheless, it requires new strategies to prevention this infections, as chlorhexidine use as a topic antiseptic prior to insertion of intravascular devices and for grooming routine in patients with central venous catheter, which is the reviewing aim this manuscript.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience.

INTRODUCTION: [corrected] Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience / Tratamento com imunossupressores em crianças com síndrome nefrótica resistente a corticosteróide: experiência de um único centro

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

INTRODUÇÃO: A síndrome nefrótica é uma das mais frequentes doenças glomerulares em crianças e o tratamento com corticosteróides ainda é o tratamento de escolha. Apesar disso, 10 a 15% dos pacientes são resistentes a corticosteróides, e o melhor tratamento para tais casos ainda não foi definido. O ácido micofenólico (AM) é um dos tratamentos usados em tais situações. OBJETIVO: Descrever o comportamento clínico de crianças diagnosticadas com síndrome nefrótica resistente a corticosteróide (SNRC) e avaliar a resposta terapêutica ao AM. MÉTODOS: Esse foi um estudo retrospectivo e descritivo. RESULTADOS: 26 registros de pacientes com SNRC; 70% homens e 30% mulheres. Todos os pacientes foram submetidos a biópsias renais, o que mostrou predominância de glomeruloesclerose segmentar focal (GESF). Os medicamentos imunossupressores utilizados foram: Mofetil Micofenolato (MMF) 100%; Ciclosporina 69,2%; Ciclosfosfamida 23,1%; e Rituximabe 23%. Um mês após início do tratamento com MMF, 61,5% tiveram remissão. A mediana das recidivas por ano para os pacientes foi de 3 (p25: 2,75 - p75: 4). Essa mediana se tornou 1 (p25: 1 - p75: 3,25) após o uso da medicação (p = 0,08). Além disso, antes do início do tratamento com MMF, a mediana da dose de corticosteróide foi de 1 (p25: 0.5 - p75: 1.62) mg/k/ dia. Após a utilização do MMF, essa mediana se tornou 0,07 (p25: 0 - p75: 0,55) mg/k/dia (p < 0,001), em 8 pacientes a prednisolona foi interrompida. CONCLUSÃO: em nossa casuística, o tratamento com MMF mostrou resultados positivos, tais como a redução na frequência de recidivas, menos proteinúria, e redução da dose de corticosteróide administrada sem deterioração nas taxas de filtração glomerular. Entretanto, mais estudos são necessários para se avaliar a eficácia, segurança e otimização da dosagem.

IgM nephropathy in children: clinicopathologic analysis.

INTRODUCTION: IgM nephropathy (IgMN) is a glomerulonephritis characterised by diffuse mesangial immunoglobulin M (IgM) deposits. It usually presents with nephrotic range proteinuria and, according to some previous work, it occurs most often in patients who are resistant to or dependent on steroid treatment. OBJECTIVE: To perform a clinical, histological and immunopathological description and assess the response to steroid treatment of paediatric patients diagnosed with nephrotic syndrome and diffuse mesangial IgM deposits. METHOD: This is a descriptive, retrospective study carried out in two hospitals, where the clinical records of paediatric patients with IgMN were analysed and the histological sections were re-assessed. RESULTS: thirteen children were included in this study. IgMN corresponded to 5.17% of all paediatric renal biopsies. The age of patients ranged from 1 year to 12 years (median: 2 years), 46.7% were women. The most common morphological finding was diffuse mesangial hypercellularity (46.1%), followed by focal segmental glomerulosclerosis (30.8%) and minimal glomerular changes (23.1%). All patients received steroids; in 4 cases (30.7%) as the only immunosuppressant medication, 3 (23.1%) also received cyclophosphamide, 5 (38.4%) mycophenolate, and 1 (7.7%) cyclosporine. Seven patients (53.8%) had frequent relapses, 5 (38.5%) were cortico-resistant and 1 (7.7%) cortico-dependent. Two patients (15.38%) had chronic impairment of renal function. CONCLUSION: The presence of diffuse mesangial IgM in paediatric patients with nephrotic syndrome is not a very uncommon finding; its clinical presentation has been associated with lower response to steroids. However, the long-term prognosis of these patients is still unknown.

Diagnóstico por imágenes en la articulación temporomandibular / Imaging diagnosis in the temporomandibular joint

La articulación temporomandibular representa un punto de interconexión muy importante entre diversas especialidades médicas y odontológicas, tales como la traumatología, neurología, otorrinolaringología, cirugía maxiofacial y ortodoncia. El odontgólo general es en muchos casos el primero en detectar disfunciones temporomandibulares iniciales o avanzadas en el caso de estar debidamente formados. Todas las especialides mencionadas anteriormente utilizan los mismos métodos de diagnóstico por imágenes como radiografías convencionales con o sin contraste, tomografías lineas, tomografías computdas, ecografías, resonancia nuclear magnética y centellografía, más un arsenal de técnicas específicas dependiendo de la especialidad y disfunción que se trate, tales como medición de potenciales evocados, sonogramas con espectro de frecuencia y amplitud, etc. Por lo tanto poder intepretar las imágenes obtenidas, constituye un importante avance en el entendimniento de tan compleja articulación.Actualmente los tratamientos de los diversos estados de disfunción temporomandibular están en permanente revisión y evolución, por lo cual, reconocidos autores como Westesson P.L. Paesani , Isberg A sugieren considerar que la curva de aprendizaje es de reciente comienzo, de modo que por el momento no es conveniente intentar formuola raxiomas(AU)

Diagnóstico por imágenes en la articulación temporomandibular / Imaging diagnosis in the temporomandibular joint

La articulación temporomandibular representa un punto de interconexión muy importante entre diversas especialidades médicas y odontológicas, tales como la traumatología, neurología, otorrinolaringología, cirugía maxiofacial y ortodoncia. El odontgólo general es en muchos casos el primero en detectar disfunciones temporomandibulares iniciales o avanzadas en el caso de estar debidamente formados. Todas las especialides mencionadas anteriormente utilizan los mismos métodos de diagnóstico por imágenes como radiografías convencionales con o sin contraste, tomografías lineas, tomografías computdas, ecografías, resonancia nuclear magnética y centellografía, más un arsenal de técnicas específicas dependiendo de la especialidad y disfunción que se trate, tales como medición de potenciales evocados, sonogramas con espectro de frecuencia y amplitud, etc. Por lo tanto poder intepretar las imágenes obtenidas, constituye un importante avance en el entendimniento de tan compleja articulación.Actualmente los tratamientos de los diversos estados de disfunción temporomandibular están en permanente revisión y evolución, por lo cual, reconocidos autores como Westesson P.L. Paesani , Isberg A sugieren considerar que la curva de aprendizaje es de reciente comienzo, de modo que por el momento no es conveniente intentar formuola raxiomas