Cohorte descriptiva de pacientes adultos con hipertensión portal en una institución de tercer nivel en Colombia / Descriptive cohort of adult patients with portal hypertension at a tertiary care institution in Colombia

Introducción. La hipertensión portal (HTP) se define como una elevación anormal de la presión venosa en el sistema portal que lleva al desarrollo de vías colaterales para desviar el flujo sanguíneo de la zona. Dentro de su etiología están las relacionadas con la cirrosis hepática y otras causas denominadas no cirróticas. El objetivo de este estudio fue evaluar los principales hallazgos demográficos, clínicos y paraclínicos en un grupo de pacientes con HTP, y determinar el uso de ayudas invasivas y no invasivas, y su disponibilidad para el diagnóstico y seguimiento de los pacientes en los centros que no cuentan con laboratorio de hemodinamia hepática, reflejando la dinámica de múltiples escenarios en Colombia. Metodología. Se realizó un estudio descriptivo de corte transversal, retrospectivo, en pacientes atendidos en una institución de tercer nivel del sur de Colombia, entre enero del año 2015 y diciembre del año 2020. Resultados. Se obtuvo una muestra de 61 pacientes en donde la mayoría de casos correspondían a hombres en la séptima década de la vida, procedentes del área urbana. La principal causa de consulta fue el sangrado digestivo (39,3 %), asociado a la presencia de telangiectasias (arañas vasculares) en el 37,2 %, seguido de circulación colateral (31,3 %) e ictericia (19,7 %). En la ecografía abdominal (realizada en el 57,4 % de los pacientes) predominaron la cirrosis (68 %) y la presencia de esplenomegalia (14,2 %), y en lospacientes con Doppler portal (realizado en el 16,4 %) se encontró hígado cirrótico (80 %) y dilatación portal (40 %). Con respecto a los hallazgos en la esofagogastroduodenoscopia predominó la presencia de várices esofágicas y gastritis crónica. Conclusión. El principal motivo de consulta fue el sangrado digestivo, en tanto que la cirrosis fue el antecedente y el hallazgo imagenológico más frecuente, seguido de las várices esofágicas. Se encontró que el uso de paraclínicos, ecografía abdominal, ecografía con Doppler portal y esofagogastroduodenoscopia fueron los más utilizados en el contexto clínico de los pacientes con el diagnóstico de HTP.

Introduction. Portal hypertension (PHT) is defined as an abnormal elevation of venous pressure in the portal system that leads to the development of collateral pathways to divert blood flow from the area. Within its etiology are those related to liver cirrhosis and other so-called non cirrhotic causes. The aim of this study was to evaluate the main demographic, clinical and paraclinical findings in a group of patients with PHT, and to determine the use of invasive and non-invasive aids, and their availability for the diagnosis and follow-up of patients in centers that do not have a hepatic hemodynamics laboratory, reflecting the dynamics of multiple scenarios in Colombia. Methodology. A descriptive, retrospective, cross-sectional, retrospective study was conducted in patients attended in a third level institution in Southern Colombia, between January 2015 and December 2020. Results. A sample of 61 patients was obtained where the majority of cases corresponded to men in the seventh decade of life, from the urban area. The main cause of consultation was digestive bleeding (39.3%), associated with the presence of telangiectasias (spider veins) in 37.2%, followed by collateral circulation (31.3%) and jaundice (19.7%). In abdominal ultrasound (performed in 57.4% of the patients), cirrhosis (68%) and the presence of splenomegaly (14.2%) predominated, and in patients with portal Doppler (performed in 16.4%), cirrhotic liver (80%) and portal dilatation (40%) were found. With respect to the findings in the esophagogastroduodenoscopy, esophageal varices and chronic gastritis were predominant. Conclusion. The main reason for consultation was gastrointestinal bleeding, while cirrhosis was the most frequent history and imaging finding, followed by esophageal varices. It was found that the use of paraclinics, abdominal ultrasound, ultrasound with portal Doppler and esophagogastroduodenoscopy were the most used in the clinical context of patients diagnosed with PHT.

Tweak/Fn14 system is involved in rhabdomyolysis-induced acute kidney injury.

BACKGROUND: Rhabdomyolysis is a severe clinical syndrome associated to acute kidney injury (AKI) and chronic kidney disease (CKD). TWEAK/Fn14 signaling axis regulates renal inflammation and tubular cell death. However, the functional role of TWEAK/Fn14 in rhabdomyolysis remains unknown. METHODS: Rhabdomyolysis was induced in wild-type, TWEAK- and Fn14-deficient mice or mice treated with TWEAK blocking antibody. Renal injury, inflammation, fibrosis and cell death were assessed. Additionally, we performed in vivo and in vitro studies to explore the possible signalling pathways involved in Fn14 regulation. FINDINGS: Fn14 renal expression was increased in mice with rhabdomyolysis, correlating with decline of renal function. Mechanistically, myoglobin (Mb) induced Fn14 expression via ERK and p38 pathway, whereas Nrf2 activation diminished Mb-mediated Fn14 upregulation in cultured renal cells. TWEAK or Fn14 genetic depletion ameliorated rhabdomyolysis-associated loss of renal function, histological damage, tubular cell death, inflammation, and expression of both tubular and endothelial injury markers. Deficiency of TWEAK or Fn14 also decreased long-term renal inflammation and fibrosis in mice with rhabdomyolysis. Finally, pharmacological treatment with a blocking TWEAK antibody diminished the expression of acute renal injury markers and cell death and lessened residual kidney fibrosis and chronic inflammation in rhabdomyolysis. INTERPRETATION: TWEAK/Fn14 axis participates in the pathogenesis of rhabdomyolysis-AKI and subsequent AKI-CKD transition. Blockade of this signaling pathway may represent a promising therapeutic strategy for reducing rhabdomyolysis-mediated renal injury. FUNDING: Spanish Ministry of Science and Innovation, ISCIII and Junta de Andalucía.

STING1 deficiency ameliorates immune-mediated crescentic glomerulonephritis in mice.

Rapidly progressive/crescentic glomerulonephritis (RPGN/CGN) involves the formation of glomerular crescents by maladaptive differentiation of parietal epithelial cells that leads to rapid loss of renal function. The molecular mechanisms of crescent formation are poorly understood. Therefore, new insights into molecular mechanisms could identify alternative therapeutic targets for RPGN/CGN. Analysis of kidney biopsies from patients with RPGN revealed increased interstitial, glomerular, and tubular expression of STING1, an accessory protein of the c-GAS-dependent DNA-sensing pathway, which was also observed in murine nephrotoxic nephritis induced by an anti-GBM antibody. STING1 was expressed by key cell types involved in RPGN and crescent formation such as glomerular parietal epithelial cells, and tubular cells as well as by inflammation accessory cells. In functional in vivo studies, Sting1-/- mice with nephrotoxic nephritis had lower kidney cytokine expression, milder kidney infiltration by innate and adaptive immune cells, and decreased disease severity. Pharmacological STING1 inhibition mirrored these findings. Direct STING1 agonism in parietal and tubular cells activated the NF-κB-dependent cytokine response and the interferon-induced genes (ISGs) program. These responses were also triggered in a STING1-dependent manner by the pro-inflammatory cytokine TWEAK. These results identify STING1 activation as a pathological mechanism in RPGN/CGN and TWEAK as an activator of STING1. Pharmacological strategies targeting STING1, or upstream regulators may therefore be potential alternatives to treat RPGN. © 2023 The Pathological Society of Great Britain and Ireland.

Feasibility and Acceptability of an Online Family Literacy Program in an Under-Resourced Community During the COVID-19 Pandemic.

OBJECTIVE: The objective of this study was to examine the feasibility and acceptability of an online family literacy program (FLP) among low-income Latino families during the COVID-19 pandemic. METHODS: We conducted a mixed methods pilot study. Latino parent-child dyads participated in an 8-week online FLP conducted on video conferencing software, developed through a cross-sector health care-education partnership. We conducted surveys and structured observation to assess feasibility and acceptability and in-depth interviews to gain insight into the context of participants' experiences during the pandemic. RESULTS: The 35 participating parent-child dyads all identified as Latino, 83% reported limited English proficiency, and 60% of parents did not achieve a high school diploma. Nearly two-thirds of families participated in at least half of the sessions. On average, parents welcomed, liked, approved, and found the program appealing. While 86% experienced a technology problem at least once during sessions, all were resolved with minimal assistance. During qualitative interviews, we identified 3 themes that provide insight into their experiences with the FLP within the broader context of the pandemic: (1) disruption in family routine and financial strain caused by COVID-19 intensified family stress, (2) the forced transition to remote learning highlighted the inequities experienced by Latino preschool children, and (3) the FLP empowered parents and enhanced health and education experiences. CONCLUSION: Latino families had high participation levels in an online FLP and found it acceptable. Additional work is needed to understand how similar primary care programs can be leveraged to promote optimal development during a time of heightened need.

Reach Out and Read Implementation: A Scoping Review.

BACKGROUND: Reach Out and Read (ROR) is an evidence-based literacy promotion intervention that leverages the near-universal access to children of primary care practices to promote optimal child development. While several studies document ROR's effectiveness, its implementation remains understudied. OBJECTIVE: This scoping review examines the existing literature to better understand ROR implementation. DATA SOURCES: PubMed, ERIC, Web of Science, Academic Search Premier, ProQuest Education Database, and CINAHL. STUDY SELECTION: We included peer-reviewed English-language papers focusing on ROR in an ambulatory setting in North America. DATA EXTRACTION: Extracted variables were informed by the Template for Intervention Description and Replication checklist and included publication year, title, author(s), clinic location, study design, study aim, ROR implementation, modifications, implementation assessment, barriers, facilitators, and outcomes. RESULTS: Seventy-one papers were included, of which 43 were research articles. We identified substantial variation in ROR implementation including differences in components delivered. A considerable number of research articles did not assess ROR implementation. The most common barriers to ROR implementation were at the system level (ie, financing and inadequate time). Modifications and enhancements to ROR are emerging; most address barriers at the clinician and family level. LIMITATIONS: This review was limited to published English language papers focusing on ROR. CONCLUSIONS: ROR implementation varies across studies, and many did not assess implementation. Consistent reporting and assessment of ROR implementation could create opportunities to better understand the mechanisms underlying ROR's effects and inform other early childhood interventions that seek to promote optimal development at the population level.

Crosstalk between TBK1/IKKε and the type I interferon pathway contributes to tubulointerstitial inflammation and kidney tubular injury.

The type I interferon (TI-IFN) pathway regulates innate immunity, inflammation, and apoptosis during infection. However, the contribution of the TI-IFN pathway or upstream signaling pathways to tubular injury in kidney disease is poorly understood. Upon observing evidence of activation of upstream regulators of the TI-IFN pathway in a transcriptomics analysis of murine kidney tubulointerstitial injury, we have now addressed the impact of the TI-IFN and upstream signaling pathways on kidney tubulointerstitial injury. In cultured tubular cells and kidney tissue, IFNα/ß binding to IFNAR activated the TI-IFN pathway and recruited antiviral interferon-stimulated genes (ISG) and NF-κB-associated proinflammatory responses. TWEAK and lipopolysaccharide (LPS) signaled through TBK1/IKKε and IRF3 to activate both ISGs and NF-κB. In addition, TWEAK recruited TLR4 to stimulate TBK1/IKKε-dependent ISG and inflammatory responses. Dual pharmacological inhibition of TBK1/IKKε with amlexanox decreased TWEAK- or LPS-induced ISG and cytokine responses, as well as cell death induced by a complex inflammatory milieu that included TWEAK. TBK1 or IRF3 siRNA prevented the TWEAK-induced ISG and inflammatory gene expression while IKKε siRNA did not. In vivo, kidney IFNAR and IFNß were increased in murine LPS and folic acid nephrotoxicity while IFNAR was increased in human kidney biopsies with tubulointerstitial damage. Inhibition of TBK1/IKKε with amlexanox or IFNAR neutralization decreased TI-IFN pathway activation and protected from kidney injury induced by folic acid or LPS. In conclusion, TI-IFNs, TWEAK, and LPS engage interrelated proinflammatory and antiviral responses in tubular cells. Moreover, inhibition of TBK1/IKKε with amlexanox, and IFNAR targeting, may protect from tubulointerstitial kidney injury.

Colgajo abdominal de patrón vertical para cobertura en miembro superior. Una opción vigente y versátil en nuestro medio / Vertical pattern abdominal flap for coverage in upper limb defects. A current and versatile option in our working environment

INTRODUCCIÓN Y OBJETIVO: Los defectos de cobertura en la extremidad superior implican alteraciones estéticas y funcionales importantes. Como primera opción son tratados mediante microcirugía, sin embargo, en las instituciones con recursos económicos insuficientes, o en las que no está disponible este servicio, como en el Hospital San Jorge de Pereira (Colombia), los colgajos a distancia cobran gran utilidad. En la actualidad, y en nuestro medio, el colgajo abdominal de patrón vertical es nuestra primera opción para la cobertura de estos defectos. MATERIAL Y MÉTODO: Estudio retrospectivo de casos atendidos en el Hospital Universitario San Jorge de Pereira (Colombia) entre 2016 y 2020, en los que se realizó cobertura de áreas cruentas en miembro superior mediante colgajo abdominal de patrón vertical. RESULTADOS: Recogimos un total de 10 colgajos, todos en varones, con una media de edad de 33.3 años. La etiología de los defectos fue quemadura eléctrica en 7 casos, accidente de tránsito en 2 y trauma cortocontundente en 1. En 9 pacientes el colgajo fue de base superior y en 1 caso de base inferior, todos bajo anestesia general con un tiempo quirúrgico de entre 90 y 120 minutos. La cobertura fue adecuada en el 100% de los casos, con una dehiscencia de sutura en zona receptora como única complicación. CONCLUSIONES: El colgajo abdominal de patrón vertical es una opción versátil, reproducible y segura, que cobra utilidad ante la ausencia de recursos o la posibilidad de realizar microcirugía. Actualmente es nuestra primera opción en cobertura de defectos en miembro superior, permitiendo obtener resultados satisfactorios con baja tasa de complicaciones

BACKGROUND AND OBJECTIVE: Coverage defects in the upper limb have significant aesthetic and functional implications. Mostly this defects are treated by microsurgery, however in some institutions with limited economical resources or unavailability of this area, distant flaps become an important option for reconstruction. The vertical pattern abdominal flap is our first choice for the coverage of these defects. METHODS: Retrospective study of cases with upper limb coverage defects treated with vertical pattern abdominal flap at the San Jorge de Pereira Hospital (Colombia) between 2016 and 2020. RESULTS: Ten vertical pattern abdominal flaps were performed, all in male patients, with a mean age of 33.3 years. The etiology of the defects was electrical burn in 7 cases, traffic accident in 2 and blunt trauma in 1. In 9 patients an upper base flap was performed and in 1 a lower base flap, all of them under general anesthesia with a surgical time between 90 and 120 minutes. Adequate coverage was obtained in 100% of the cases, with suture dehiscence in flap area as the only complication. CONCLUSIONS: Vertical pattern abdominal flap is a versatile, reproducible, and safe option, useful in absence of resources or the possibility of performing microsurgery, Currently, it is our first option in upper limb covering defects, allowing to obtain satisfactory results with low complication rate

Cuantificación digital de integración de injertos de piel de espesor parcial ocluidos con sistema de presión negativa / Digital quantification of integration in occluded partial-thickness skin grafts with negative pressure system

INTRODUCCIÓN Y OBJETIVO: El éxito en la integración de los injertos de piel de espesor parcial no depende de un solo factor, siendo uno de los más importantes el método de curación que se le realiza al injerto. Por tal razón, el objetivo de nuestro estudio es demostrar, a través de un programa digital informático, el porcentaje de integración que tienen los injertos de piel de espesor parcial a los que se realizó curación oclusiva con sistema de presión negativa. MATERIAL Y MÉTODO: Estudio descriptivo retrospectivo que toma como muestra todos los pacientes con defectos de cobertura y lecho receptor con tejido de granulación óptimo para realizar injerto de piel de espesor parcial, del Servicio de Cirugía Plástica de la Clínica Reina Catalina sede Barranquilla y Baranoa, en Colombia, desde el 1 de enero de 2019 hasta 31 de diciembre del mismo año. Empleamos el sistema de presión negativa WoundPro(R) (Ї#x00a9;2020 Pensar Medical, LLC) y posteriormente cuantificamos la integración de los injertos de forma digital a través de un programa de procesamiento de imágenes (ImageJ(R)), complementado con un desarrollo informático del Área de Sistemas de la Clínica para obtener un resultado matemático que permitiera, de manera más objetiva, evaluar la integración del injerto. RESULTADOS: Revisamos 70 pacientes, de los que 42 eran varones, con una edad promedio de 41.8 años. La etiología más común fue la quemadura (34%), el área anatómica de mayor incidencia fue la pierna (27.7%) y el porcentaje promedio de integración fue del 98.4%. Aplicamos el sistema de presión negativa durante 6 días para luego retirarlo y proceder a la toma de imagen fotográfica que usamos como insumo para el cálculo de la integración; tras la primera cura, el paciente es egresado y realizamos seguimiento ambulatorio, con una media de curación del área injertada de 17 días. CONCLUSIONES: En nuestra experiencia, el uso del sistema de presión negativa como método de curación oclusiva en los injertos de piel parcial, presenta tasas de éxito superiores al 98% en la integración de los injertos, lo cual se traduce en un tratamiento coste - efectivo ya que reduce las complicaciones inherentes al procedimiento. Así mismo, el cálculo matemático de la integración del injerto permite evaluar y definir de forma específica la conducta en cada caso

BACKGROUND AND OBJECTIVE: Success in the integration of partial thickness skin grafts does not depend on a single factor; one of the most important factors is the healing method performed on the skin graft. For this reason, the objective of our study is to demonstrate the percentage of integration through a digital computer program of the partial thickness skin grafts that underwent occlusive healing with the use of the negative pressure system. METHODS: Retrospective descriptive study. All patients with coverage defects, who had a wound with optimal granulation tissue to perform the partial thickness skin graft, were taken as a sample in the Plastic Surgery Service of the Reina Catalina Clinic in Barranquilla and Baranoa in Colombia, from January 1, 2019 to December 31 of the same year. For this, the WoundPro(R) negative pressure system (Ї#x00a9;2020 Pensar Medical, LLC) was used and the integration of the grafts was digitally quantified throug an image processing program (ImageJ(R)) complemented with a computerized developer of the Systems Area of the Clinic to obtain a mathematical result that would allow, more objectively, to evaluate the integration of the graft. RESULTS: Seventy patients were part of the study, the male gender was the most affected with 42 cases, the average age was 41.8 years. The most common etiology was burn (34%), the anatomical area with the highest incidence was the leg (27.7%) and the percentage integration average was 98.4%. The negative pressure system was applied for 6 days, then it was removed and the photographic record was made; that image was used to calculate the integration. After the first cure, the patient was discharged and follow-up was performed on an outpatient basis, with a healing average of the grafted area of 17 days. CONCLUSIONS: In our experience, the use of the negative pressure system as an occlusive healing method in partial skin grafts has represented success rates greater than 98% in the integration of the grafts, which translates into a cost-effective treatment since it reduces the complications inherent to this procedure. Likewise, the mathematical calculation of the graft integration makes possible the specific evaluation and definition of the behavior in each case

Effective Nephroprotection Against Acute Kidney Injury with a Star-Shaped Polyglutamate-Curcuminoid Conjugate.

The lack of effective pharmacological treatments for acute kidney injury (AKI) remains a significant public health problem. Given the involvement of apoptosis and regulated necrosis in the initiation and progression of AKI, the inhibition of cell death may contribute to AKI prevention/recovery. Curcuminoids are a family of plant polyphenols that exhibit attractive biological properties that make them potentially suitable for AKI treatment. Now, in cultured tubular cells, we demonstrated that a crosslinked self-assembled star-shaped polyglutamate (PGA) conjugate of bisdemethoxycurcumin (St-PGA-CL-BDMC) inhibits apoptosis and necroptosis induced by Tweak/TNFα/IFNγ alone or concomitant to caspase inhibition. St-PGA-CL-BDMC also reduced NF-κB activation and subsequent gene transcription. In vivo, St-PGA-CL-BDMC prevented renal cell loss and preserved renal function in mice with folic acid-induced AKI. Mechanistically, St-PGA-CL-BDMC inhibited AKI-induced apoptosis and expression of ferroptosis markers and also decreased the kidney expression of genes involved in tubular damage and inflammation, while preserving the kidney expression of the protective factor, Klotho. Thus, due to renal accumulation and attractive pharmacological properties, the application of PGA-based therapeutics may improve nephroprotective properties of current AKI treatments.