Macrophages allocate before apoptosis initiation and produce reactive oxygen species during interdigital phagocytosis.

During programmed cell death (PCD), it is commonly accepted that macrophages are recruited by apoptotic cells to complete cell degradation. Interdigital cell death, a classical model of PCD, contributes to digit individualization in limbs of mammals and other vertebrates. Here, we show that macrophages are present in interdigits before significant cell death occurs and remain after apoptosis inhibition. The typical interdigital phagocytic activity was not observed after a partial depletion of macrophages and was markedly reduced by engulfment/phagosome maturation inhibition, as detected by its association with high lysosomal activity. ß-galactosidase activity in this region was also coupled with phagocytosis, against its relationship with cellular senescence. Interdigital phagocytosis correlated with high levels of reactive oxygen species (ROS), common in embryo regions carrying abundant cell death, suggesting that macrophages are the major source of ROS. ROS generation was dependent on NADPH oxidases and blood vessel integrity, but not directly associated with lysosomal activity. Therefore, macrophages prepattern regions where abundant cell death is going to occur, and high lysosomal activity and the generation of ROS by an oxidative burst-like phenomenon are activities of phagocytosis.

The loss of antioxidant activities impairs intestinal epithelium homeostasis by altering lipid metabolism.

Reactive oxygens species (ROS) are common byproducts of metabolic reactions and could be at the origin of many diseases of the elderly. Here we investigated the role of ROS in the renewal of the intestinal epithelium in mice lacking catalase (CAT) and/or nicotinamide nucleotide transhydrogenase (NNT) activities. Cat-/- mice have delayed intestinal epithelium renewal and were prone to develop necrotizing enterocolitis upon starvation. Interestingly, crypts lacking CAT showed fewer intestinal stem cells (ISC) and lower stem cell activity than wild-type. In contrast, crypts lacking NNT showed a similar number of ISCs as wild-type but increased stem cell activity, which was also impaired by the loss of CAT. No alteration in the number of Paneth cells (PCs) was observed in crypts of either Cat-/- or Nnt-/- mice, but they showed an evident decline in the amount of lysozyme. Cat deficiency caused fat accumulation in crypts, and a fall in the remarkable high amount of adipose triglyceride lipase (ATGL) in PCs. Notably, the low levels of ATGL in the intestine of Cat -/- mice increased after a treatment with the antioxidant N-acetyl-L-cysteine. Supporting a role of ATGL in the regulation of ISC activity, its inhibition halt intestinal organoid development. These data suggest that the reduction in the renewal capacity of intestine originates from fatty acid metabolic alterations caused by peroxisomal ROS.

Utility of a clinical risk scale to predict the requirement of advanced airway management in patients with a diagnosis of deep neck abscess.

OBJECTIVES: To analyze the clinical utility of a clinical risk scale to predict the need for advanced airway management in patients with deep neck abscess. METHODS: Observational, analytical, cross-sectional study. Patients over 18 years old, both genders, with surgical management of a deep neck abscess, between January 1st, 2015 to December 31th, 2021, who were applied the clinical risk scale (https://7-414-5-19.shinyapps.io/ClinicalRiskScore/). The sensitivity, specificity, and predictive values of the scale were calculated based on the identified clinical outcomes. A p<0.05 was considered significant. RESULTS: A sample of 213 patients was obtained, 121 (56.8%) men, of whom 50 (23.5%) required advanced airway management. Dyspnea was the variable with the most statistical weight in our study, (p=0.001) as well as the multiple spaces involvement, (p=0.001) the presence of air corpuscles, (p=0.001) compromise of the retropharyngeal space (p=0.001) and age greater than 55 years (p=0.001). Taking these data into account, were found for the clinical risk scale a sensitivity of 97% and a specificity of 65% (p=0.001, 95% CI 0.856-0.984). CONCLUSIONS: The clinical risk scale developed to predict advanced airway management in patients with a diagnosis of deep neck abscess may be applicable in our environment with high sensitivity and specificity. LEVEL OF EVIDENCE: IV.

Utility of a clinical risk scale to predict the requirement of advanced airway management in patients with a diagnosis of deep neck abscess,

Abstract Objectives To analyze the clinical utility of a clinical risk scale to predict the need for advanced airway management in patients with deep neck abscess. Methods Observational, analytical, cross-sectional study. Patients over 18 years old, both genders, with surgical management of a deep neck abscess, between January 1st, 2015 to December 31th, 2021, who were applied the clinical risk scale (https://7-414-5-19.shinyapps.io/ClinicalRiskScore/). The sensitivity, specificity, and predictive values of the scale were calculated based on the identified clinical outcomes. A p < 0.05 was considered significant. Results A sample of 213 patients was obtained, 121 (56.8%) men, of whom 50 (23.5%) required advanced airway management. Dyspnea was the variable with the most statistical weight in our study, (p = 0.001) as well as the multiple spaces involvement, (p = 0.001) the presence of air corpuscles, (p = 0.001) compromise of the retropharyngeal space (p = 0.001) and age greater than 55 years (p = 0.001). Taking these data into account, were found for the clinical risk scale a sensitivity of 97% and a specificity of 65% (p = 0.001, 95% CI 0.856-0.984). Conclusions The clinical risk scale developed to predict advanced airway management in patients with a diagnosis of deep neck abscess may be applicable in our environment with high sensitivity and specificity. Level of evidence: IV.

Resultados maternos y fetales en mujeres embarazadas con enfermedad renal crónica basada en la tasa de filtración glomerular / Maternal And Fetal Outcomes In Pregnant Women With Chronic Kidney Disease Based On Glomerular Filtration Rate

Introducción: el embarazo causa adaptaciones en el riñón, tanto en anatomía como en función, para mantener el entorno extracelular, hemodinámico y hormonal. Sin embargo, estos pueden no llevarse a cabo de manera completamente óptima en presencia de enfermedad renal. El objetivo era estudiar la relación entre la enfermedad renal y los resultados maternos de fetal durante el embarazo, asociado con un rechazo por paciente y/o en relación con el tratamiento especializado. Material y métodos: estudio observacional y retrospectivo en una serie de casos, revisando 134 archivos de pacientes embarazadas con cierto grado de enfermedad renal antes del embarazo. Los resultados maternos registrados fueron: enfermedad hipertensiva durante el embarazo, deterioro renal agudo, necesidad de terapia de sustitución renal y en productos: prematuridad, restricción del crecimiento intrauterino, muerte fetal y aborto espontáneo. Resultados: Resultados maternos: tasa media de filtración glomerular (GFR) de 58.23 ml/min, aumento de peso de 7 kg; La preeclampsia fue diagnosticada en 92 mujeres (55 severas). 46 pacientes mostraron lesión renal aguda, 40 se resolvieron conservativamente; 1 requirió diálisis peritoneal y 15 hemodiálisis (con una decisión retrasada un promedio de un mes por rechazo por paciente y/o pariente). La resolución del embarazo fue por cesárea en 111 pacientes; Nacieron 116 productos antes de las 37 semanas de gestación, con un peso promedio de 1910 g, 94 mostraron restricción del crecimiento intrauterino. Conclusión: la enfermedad renal influyó directamente en el mayor número de resultados adversos maternos y fetales cuando se rechazó la atención médica especializada. Existe una correlación entre el ligero estado de Davison con los estados I, II y IIIA de Kdigo en el análisis de correspondencia

Introduction: Pregnancy causes adaptations in the kidney, both in anatomy and function, to maintain the extracellular, hemodynamic and hormonal environment. However, these may not be carried out completely optimally in the presence of kidney disease. The objective was to study the relation between kidney disease and maternal-fetal outcomes during pregnancy, associated with a rejection by patient and/or relative to specialized treatment. Material and Methods: Observational, retrospective study in a series of cases, reviewing 134 files of pregnant patients with some degree of kidney disease prior to pregnancy. Maternal outcomes recorded were: hypertensive disease during pregnancy, acute renal deterioration, need for renal substitution therapy, and in products: prematurity, restriction of intrauterine growth, fetal death and miscarriage. Results: Maternal outcomes: mean glomerular filtration rate (GFR) of 58.23ml/min, weight gain of 7 kg; preeclampsia was diagnosed in 92 women (55 severe). 46 patients showed acute renal lesion, 40 were conservatively resolved; 1 required peritoneal dialysis and 15 hemodialysis (with decision delayed an average of one month by rejection by patient and/or relative). Resolution of pregnancy was by cesarean in 111 patients; 116 products were born before 37 weeks of gestation, with average weight of 1910 g, 94 showed restriction of intrauterine growth. Conclusion: Kidney disease directly influenced the greater number of adverse maternal and fetal outcomes when specialized medical care was rejected. There is a correlation between slight Davison state with states I, II and IIIa of KDIGO in correspondence analysis.

[Risk factors at admission associated with intubation in patients with COVID-19]. / Factores de riesgo al ingreso asociados a intubación en pacientes con COVID-19.

Background: Intubation rates up to 33% have been found in patients diagnosed with COVID-19. Some cohorts have reported the presence of dyspnea in 84.1% of intubated patients, being this the only symptom associated with intubation. Oxygen saturation < 90% and increased respiratory rate have also been described as predictors of intubation. Objective: To analyze the risk factors associated with intubation in patients hospitalized for COVID-19 at their admission. Material and methods: An observational, retrospective, analytical, cross-sectional study was carried out. The universe of study consisted of patients over 18 years of age hospitalized due to a diagnosis of SARS-CoV-2 virus infection from April 1, 2020 to April 31, 2021 in the Hospital de Especialidades (Specialties Hospital) "Dr. Bernardo Sepúlveda Gutiérrez" at the National Medical Center. Results: The mean age of intubated patients was 59.17 years (95% confidence interval [95% CI] -9.994 to -3.299, p < 0.001). Overall, 76.7% (230) of patients had a history of one or more preexisting comorbidities, including hypertension in 42.3% (127), obesity in 36.7% (110), and diabetes mellitus in 34.3% (103). Conclusions: The main clinical characteristics of patients hospitalized for COVID-19 in our center who required intubation are very similar to those observed in different centers, including male sex, age over 50 years and obesity, which were the most common.

Introducción: se han encontrado tasas de intubación de hasta 33% en pacientes con diagnóstico de COVID-19. Algunas cohortes han informado la presencia de disnea en el 84.1% de los pacientes intubados y este ha sido el único síntoma asociado con la intubación. La saturación de oxígeno < 90% y el aumento de la frecuencia respiratoria también han sido descritos como predictores de intubación. Objetivo: analizar los factores de riesgo asociados a intubación en pacientes con COVID-19 al momento de su admisión hospitalaria. Material y métodos: se realizó un estudio observacional, transversal, analítico y retrospectivo. El universo de estudio consistió en pacientes mayores de 18 años, hospitalizados por diagnóstico de infección por virus SARS-CoV-2 del 1 abril de 2020 al 31 abril de 2021 en el Hospital de Especialidades "Dr. Bernardo Sepúlveda Gutiérrez" del Centro Médico Nacional. Resultados: se analizaron un total de 300 pacientes. La media de edad de los pacientes intubados fue de 59.17 años (p < 0.001, intervalo de confianza del 95% [IC 95%] −9.994 a −3.299). En general, el 76.7% (230) de los pacientes tenía antecedentes de una o más comorbilidades preexistentes, incluida la hipertensión en 42.3% (127), la obesidad en 36.7% (110) y la diabetes mellitus en 34.3% (103). Conclusiones: las principales características clínicas de los pacientes hospitalizados por COVID-19 en nuestro centro que requirieron de intubación son muy similares a las observadas en distintos centros, entre ellas el sexo masculino, la edad mayor de 50 años y la obesidad, que fueron las más prevalentes.

Asociación del signo de Moore con la presencia de absceso profundo de cuello de espacio retrofaríngeo.

BACKGROUND: Deep neck abscesses can cause life-threatening complications. They are diagnosed by physical examination, and contrasted tomography as the gold standard. There are no studies about the association of Moore's sign with infections of the retropharyngeal space. OBJECTIVE: To determine the usefulness of Moore's sign in the diagnosis of deep retropharyngeal abscess. METHOD: Observational, analytical, cross-sectional, study of patients with deep neck abscess, from May 1, 2019, to August 30, 2021, with report of Moore's sign. RESULTS: 87 patients were included, 49 (56.3%) males (p = 0.45). Of those who developed complications, 77.8% had a negative Moore's sign (p = 0.001). Of those admitted to the ICU, 72% had a negative Moore's sign (p = 0.001). The sensitivity of the absence of the sign with retropharyngeal involvement was 95.4%, and the specificity was 86.3%. By logistic regression, it was found that those with retropharyngeal involvement are 467 times more likely to present a negative sign (p < 0.05). CONCLUSIONS: The presence of abscess in the retropharynx is associated with complications and a worse prognosis. The evaluation of Moore's sign can be a useful tool to suspect compromise of this space.

ANTECEDENTES: Los abscesos profundos de cuello pueden ocasionar complicaciones letales. Se diagnostican por exploración física, y la tomografía contrastada es el método de referencia. No existen estudios de asociación del signo de Moore con infecciones del espacio retrofaríngeo. OBJETIVO: Determinar la utilidad del signo de Moore en el diagnóstico de absceso profundo en el espacio retrofaríngeo. MÉTODO: Estudio observacional, transversal y analítico, de pacientes con absceso profundo de cuello, del 1 de mayo de 2019 al 30 de agosto de 2021, con reporte de signo de Moore. RESULTADOS: Se incluyeron 87 pacientes, de los cuales 49 (56.3%) eran de sexo masculino (p = 0.45). De los que desarrollaron complicaciones, el 77.8%, tenían el signo de Moore negativo (p = 0.001). De los que ingresaron a la unidad de cuidados intensivos, el 72% tenían negativo el signo de Moore (p = 0.001). La sensibilidad de la ausencia del signo con afección del espacio retrofaríngeo fue del 95.4%, y la especificidad del 86.3%. Por regresión logística se encontró que aquellos con afección del espacio retrofaríngeo tienen 467 veces más posibilidades de presentar signo negativo (p < 0.05). CONCLUSIONES: La presencia de un absceso en el espacio retrofaríngeo se asocia a complicaciones y peor pronóstico. La evaluación del signo de Moore puede ser una herramienta útil para sospechar compromiso de ese espacio.

Retroperitoneal Teratoma in a Transplanted Patient: Case Report and Review.

BACKGROUND: The development of de novo neoplasms in solid organ transplantation is multifactorial. In addition to common factors in the general population, there are specific factors of the disease related or not to chronic renal failure and factors inherent to the transplant itself such as immunosuppression. OBJECTIVE: The aim of this study is to describe the case of a kidney recipient with a retroperitoneal teratoma, his satisfactory treatment, and a brief literature review. METHODS: The case of 59-year-old male patient who received a living donor transplant in 2011, with conventional immunosuppression, graft protocol biopsy per year reported as normal, and follow-up without eventualities is described. The patient's symptoms began in December 2020 with abdominal pain resistant to analgesics, asthenia, and adynamic. Contrast tomography showed a retroperitoneal tumor 25.8 × 16.9 × 19 cm; tumor markers: alpha fetoprotein, 2.16 ng/mL; cancer antigen 19-9, 524.5 UI/ml; and carcinoembryonic antigen, 67.53 ng/mL. Resection of a 25 × 25 × 20 cm retroperitoneal tumor between the vena cava and aorta with 2 L of mucus content was performed. The patient was discharged from the hospital on the second day, with uresis 1 mL/kg/h, and at one month with adequate renal function, and 0.94 mg/dL of serum creatinine. A definitive histologic report was compatible with retroperitoneal mature teratoma. CONCLUSION: Primary retroperitoneal mature teratoma is rarely evidenced in adult patients, usually asymptomatic, and the definitive diagnosis always is established after histologic evaluation. Surgical resection is the main treatment with the complete removal of the tumor and long-term monitoring is needed because of the risk of malignancy.

Mortality Due to COVID-19 in Renal Transplant Recipients, Related to Variants of SARS-CoV-2 and Vaccination in Mexico.

BACKGROUND: SARS-CoV-2 infection in transplant patients has shown greater lethality and vaccination in this group of patients has shown less information. The objective of this study is to show the statistics in Mexico of lethality in kidney recipients infected with COVID-19 in relation to vaccination and variants of the coronavirus. METHODS: This is a bibliographic search of kidney transplant recipient patients since the start of the pandemic in Mexico to determine lethality after SARS-CoV-2 compared to the general population and in relation to patients, the 4 most important infectious peaks in the country due to identified variants, and also before and after vaccination. RESULTS: The global lethality is 26.91% from the beginning of the pandemic to April 9, 2022 in kidney recipients in Mexico (130 deaths of 483 infected kidney transplant recipients) compared to the national lethality of 5.60%. Variant B. 1.1.220 represented the highest lethality with 30.43% and the lowest lethality was Omicron with 16.41%. The lethality prior to vaccination was 30.94% and 23.46% after it. CONCLUSION: Both some variants and vaccination have influenced a lower lethality due to COVID-19 in Mexico in kidney transplant patients; It is important to consider global recommendations, such as a third or fourth dose, a combination of mRNA vaccines and vectors in order to reduce lethality in this group of patients.

Dll1 haploinsufficiency causes brain abnormalities with functional relevance.

Introduction: The Notch pathway is fundamental for the generation of neurons during development. We previously reported that adult mice heterozygous for the null allele of the gene encoding the Delta-like ligand 1 for Notch (Dll1lacZ ) have a reduced neuronal density in the substantia nigra pars compacta. The aim of the present work was to evaluate whether this alteration extends to other brain structures and the behavioral consequences of affected subjects. Methods: Brains of Dll1 +/lacZ embryos and mice at different ages were phenotypically compared against their wild type (WT) counterpart. Afterwards, brain histological analyses were performed followed by determinations of neural cell markers in tissue slices. Neurological deficits were diagnosed by applying different behavioral tests to Dll1 +/lacZ and WT mice. Results: Brain weight and size of Dll1 +/lacZ mice was significantly decreased compared with WT littermates (i.e., microcephaly), a phenotype detected early after birth. Interestingly, enlarged ventricles (i.e., hydrocephalus) was a common characteristic of brains of Dll1 haploinsufficient mice since early ages. At the cell level, general cell density and number of neurons in several brain regions, including the cortex and hippocampus, of Dll1 +/lacZ mice were reduced as compared with those regions of WT mice. Also, fewer neural stem cells were particularly found in the adult dentate gyrus of Dll1 +/lacZ mice but not in the subventricular zone. High myelination levels detected at early postnatal ages (P7-P24) were an additional penetrant phenotype in Dll1 +/lacZ mice, observation that was consistent with premature oligodendrocyte differentiation. After applying a set of behavioral tests, mild neurological alterations were detected that caused changes in motor behaviors and a deficit in object categorization. Discussion: Our observations suggest that Dll1 haploinsufficiency limits Notch signaling during brain development which, on one hand, leads to reduced brain cell density and causes microcephaly and hydrocephalus phenotypes and, on the other, alters the myelination process after birth. The severity of these defects could reach levels that affect normal brain function. Therefore, Dll1 haploinsufficiency is a risk factor that predisposes the brain to develop abnormalities with functional consequences.

Establishing consensus on the perioperative management of cholecystectomy in public hospitals: a Delphi study with an expert panel in Mexico.

BACKGROUND: Several guidelines have put forward recommendations about the perioperative process of cholecystectomy. Despite the recommendations, controversy remains concerning several topics, especially in low- and middle-income countries. The aim of this study was to develop uniform recommendations for perioperative practices in cholecystectomy in Mexico to standardize this process and save public health system resources. METHODS: A modified Delphi method was used. An expert panel of 23 surgeons anonymously completed two rounds of responses to a 29-item questionnaire with 110 possible answers. The consensus was assessed using the percentage of responders agreeing on each question. RESULTS: From the 29 questions, the study generated 27 recommendations based on 20 (69.0%) questions reaching consensus, one that was considered uncertain (3.4%), and six (20.7%) items that remained open questions. In two (6.9%) cases, no consensus was reached, and no recommendation could be made. CONCLUSIONS: This study provides recommendations for the perioperative management of cholecystectomy in public hospitals in Mexico. As a guide for public institutions in low- and middle-income countries, the study identifies recommendations for perioperative tests and evaluations, perioperative decision making, postoperative interventions and institutional investment, that might ensure the safe practice of cholecystectomy and contribute to conserving resources.

The levels of reprogramming factors influence the induction and maintenance of pluripotency: the case of CD1 mouse strain cells.

The amount of proteins of the regulatory pluripotency network can be determinant for somatic cell reprogramming into induced pluripotent stem cells (iPSCs) as well as for the maintenance of pluripotent stem cells (PSCs). Here, we report a transposon-based reprogramming system (PB-Booster) that allowed high expression levels of a polycistronic transgene containing Myc, Klf4, Oct4 and Sox2 (MKOS) and showed increased reprogramming efficiency of fresh mouse embryonic fibroblasts (MEFs) into iPSCs under low, but not under high, MKOS expression levels. In contrast, MEFs after 2 passages derived into a similar number of iPSC colonies as fresh MEFs at a high MKOS dose, but this number was reduced at a low MKOS dose. Timing of reprogramming was not affected by MKOS expression levels but, importantly, exogenous MKOS expression in established PSCs caused a significant cell loss. At high but not at low MKOS expression levels, MEFs of the CD1 strain produced more initial cell clusters than iPSCs and, although reprogrammed at a similar efficiency as MEFs of the 129/Sv strain, iPSCs could not be maintained in the absence of exogenous MKOS. In CD1-iPSCs, Oct4, Nanog, Rex1 and Esrrb expression levels were reduced when compared with the levels in PSCs derived from the 129/Sv strain. Culture of CD1-iPSCs in medium with MEK and GSK3ß inhibitors allowed their self-renewal in the absence of exogenous MKOS, but the expression levels of Oct4, Nanog, Rex1 and Esrrb were only partially increased. Despite the reduced levels of those pluripotency factors, CD1-iPSC kept high capacity for contribution to chimeric mouse embryos. Therefore, levels of regulatory pluripotency factors influence reprogramming initiation and PSC maintenance in vitro without affecting their differentiation potential in vivo.

Survival of Vascular Accesses in Chronic Hemodialysis Patients.

BACKGROUND/AIMS: Vascular access (VA) is the highest risk factor for blood infections, hospitalization, and mortality of patients undergoing hemodialysis (HD). The risk of mortality while using a catheter is greater than that while using grafts. The objective of this article is to know the survival rate in relation to the type of VA. METHODS: A retrospective cohort of HD patients was studied. The data gathered included age, gender, first VA at the surrogate site, days between the first and second access, number of accesses, and anatomical site of VA placement. Mean differences were estimated using χ2 or Student's t test. Survival was calculated using the Kaplan-Meier curves and included in tables. Statistical significance was established as p < 0.05. The statistical computer software package SPSSw v25 was used for the analysis. RESULTS: A total of 896 patients were included with a mean age of 47.88 years (SD ± 16.52), the duration of the first VA was 398.81 days (±565.79), the mean number of VAs used was 2.26 (±1.15), and the median time undergoing HD was 728.73 days. The duration of catheter placement was 330.42 days, and 728.60 days for fistula use (p = 0.001). The mean number of days of renal replacement was 611.59 days for catheter and 1,495.25 days for internal arteriovenous fistula (IAVF) patients (p = 0.001). CONCLUSIONS: The survival of the initial VA is greater for the IAVF, followed by the tunneled catheters and the lowest by the non-tunneled catheters, which continue to be frequently used in our setting.

Interleukin 8 Is Overexpressed in Acute Rejection in Kidney Transplant Patients.

The main complication associated with renal graft loss is immune rejection. The gold standard for the diagnosis of renal graft rejection is percutaneous renal biopsy, which is expensive and can lead to complications. Inflammation is one of the main pathogenic pathways in allograft rejection, and urine samples seem to be efficient windows to explore the allograft condition with a high cost-benefit ratio. This study aimed to evaluate the messenger ribonucleic acid (mRNA) profile expression pattern for interleukin (IL) 2, IL-4, IL-6, IL-8, and IL-10; tumor necrosis factor alfa; gamma interferon; and transforming growth factor ß1 in the urine renal cells of patients with a diagnosis of humoral rejection and patients with a diagnosis of normal biopsy. METHODS: An observational, cross-sectional analytical study was performed. All kidney transplants were performed at the Organ Transplant Department between 2018 and 2019. Also, a healthy control with a normal blood test and no apparent infection was included. mRNA from urine samples and biopsies was isolated, and the expression of interleukins was analyzed in PCR real time. Data were analyzed by Shapiro-Wilk and Kruskal-Wallis tests. RESULTS: The proinflammatory IL expression pattern in urine samples of kidney rejection group showed overexpression for IL-8 (P = .0001). No differences were observed in the rest of the interleukins analyzed. When we compared the results in the rejected versus not rejected transplanted patients with a group of apparently healthy subjects, the difference remains consistent. Thus, mRNA of IL-8 could function as a diagnostic tool in cases of chronic damage secondary to fibrosis.

Kidney Donor Profile Index in a Transplant Center in Mexico.

BACKGROUND: The Kidney Donor Profile Index (KDPI) was created in 2014 to measure the likelihood of graft failure for a given donor compared with the median kidney donor from the previous year. This scale is based on the American population only. Mexico is one of the countries with greater incidence of chronic kidney disease, a long waiting list, and not enough kidney donors with KDPI smaller than 80%. This has led transplant centers to take kidney grafts with a higher KDPI. OBJECTIVE: To investigate the agreement between the KDPI and histologic scores (preimplantation renal biopsy) and assess the relationship between the Kidney Donor Risk Index (KDRI), KDPI, and the histologic score on graft survival. METHODS: A retrospective, analytical, transversal study was performed. Data were collected from patients with kidney grafts from deceased donors from January 1, 2011, to June 30, 2019, at our hospital. The variables analyzed were age, weight, height, sex, race and/or ethnicity, history of hypertension or diabetes, cause of death, serum creatinine, KDPI, KDRI, and biopsy result from each graft prior to transplant. RESULTS: The total population was 59 deceased kidney donors. For our patients, a high KDPI did not increase mortality rate; it provided greater benefit than staying on dialysis. CONCLUSIONS: We conclude that the use of KDRI should only be considered to assess the degree of fibrosis, not to rule out a transplantable kidney, in addition to the consistent demonstration that high KDPI kidneys (even 91%-100%) confer greater survival benefits to patients regarding the waiting list.

Analyses of Programmed Cell Death Protein 1 in High Immunologic-Risk Transplant Patients.

Kidney transplant (KT) is the first therapeutic option for most patients with chronic renal failure that requires renal function replacement. The main complication associated with renal graft loss is immune rejection. The T regulatory pathways play a key role in this process, and abnormalities in some of these molecules could participate in the graft rejection. In this paper, our group performed an exploratory analysis of the behavior of the coinducible molecules (CD28, CTLA-4, ICOS, PD-1) in patients with KT rejection and control KT patients without rejection. The Mann-Whitney U test, used for 2 groups, showed significant differences (P = .0005), indicating that PD-1 is underexpressed in patients with allograft rejection. No differences were found in CD28+, regulatory T cells (T reg), CTLA-4, and ICOS, so we are proposing that PD-1 is a key player in the immunotolerance phenomenon and its underexpression participates in the rejection process. More research needs to be performed on this topic.

The nuclear receptor NR4A1 is regulated by SUMO modification to induce autophagic cell death.

NR4A is a nuclear receptor protein family whose members act as sensors of cellular environment and regulate multiple processes such as metabolism, proliferation, migration, apoptosis, and autophagy. Since the ligand binding domains of these receptors have no cavity for ligand interaction, their function is most likely regulated by protein abundance and post-translational modifications. In particular, NR4A1 is regulated by protein abundance, phosphorylation, and subcellular distribution (nuclear-cytoplasmic translocation), and acts both as a transcription factor and as a regulator of other interacting proteins. SUMOylation is a post-translational modification that can affect protein stability, transcriptional activity, alter protein-protein interactions and modify intracellular localization of target proteins. In the present study we evaluated the role of SUMOylation as a posttranslational modification that can regulate the activity of NR4A1 to induce autophagy-dependent cell death. We focused on a model potentially relevant for neuronal cell death and demonstrated that NR4A1 needs to be SUMOylated to induce autophagic cell death. We observed that a triple mutant in SUMOylation sites has reduced SUMOylation, increased transcriptional activity, altered intracellular distribution, and more importantly, its ability to induce autophagic cell death is impaired.

Compliance With Biochemical Objectives in Patients on Renal Replacement Therapy Before Kidney Transplantation in Mexico.

OBJECTIVES: The biochemical conditions in which patients arrive before renal transplantation (RT) are rarely evaluated; examples of them are found in the Dialysis Outcomes and Practice Patterns Study (DOPPS). The objective of our study was to ascertain the fulfillment of biochemical goals for patients on renal replacement therapy before RT. MATERIAL AND METHODS: Observational, retrospective study of patients who were on a RT protocol between 2012 and 2017 in 2 RT centers in Mexico. The records of 1188 patients with a history of RT and their lab results before transplantation were analyzed. Anthropometric values including hemoglobin, iron levels, calcium, phosphorus, parathyroid hormone, urea, creatinine, uric acid, and left ventricular ejection fraction were studied. All values were categorized as low, optimal, or high levels. RESULTS: The fulfillment of pretransplant biochemical objectives for elimination of azotemia (urea and creatinine) was achieved in 60% of the patients. Optimal values for calcium were found in 715 (64%) patients and optimal values for albumin were found in 690 (61.8%) patients. In the case of phosphorus, hemoglobin, uric acid, and parathyroid hormone, the optimal values were below 50%. CONCLUSIONS: It is essential to improve compliance with biochemical and clinical objectives for patients on renal replacement therapy (dialysis, hemodialysis) before RT. Only half of the variables were within the optimal range before surgical intervention took place.

Post-Transplant Cholesterol and Triglyceride Behavior: Effects of Sex, Age of the Recipient, and Type of Donor.

BACKGROUND: Dyslipidemia represents a trigger for cardiovascular complications, being in minimized renal transplantation (RT) or most of the occasions associated as something secondary to immunosuppression. The objective is to determine the pattern of cholesterol and triglyceride behavior in the first 12 months of post-transplant evolution and its relationship with age, sex of the recipient, and type of renal donor. MATERIALS AND METHODS: An observational, longitudinal study of RT carried out from 2013 to 2017 at the National Medical Center La Raza. In total, 328 records of patients with RT were analyzed. Cholesterol and triglyceride levels were studied over 12 months after renal transplantation; the association with sex, age of the renal recipient, and type of donor (live or deceased) was determined. Measures of central tendency and dispersion were made; the difference of means was established with a χ2 or Student t test. For risk, a bivariate analysis was performed with a significant value of P < .05. SPSS version 25 (IBM, Armonk, NY, United States) was used. RESULTS: The mean pretransplant cholesterol was within normal values (176.32, standard deviation [SD] 40.15 mg/dL), but triglycerides were not (158.36, SD 36.60 mg/dL). The pattern in both cases increased the values the first month after transplant to reach similar pretransplant levels in month 12. Cholesterol showed differences for month 12 in the group over 50 years (P = .022); like triglycerides in the 9th and 12th months (P = .026 and .003, respectively), values were higher in those over 50 years. DISCUSSION AND CONCLUSIONS: The pattern of cholesterol and triglyceride behavior is similar, even without understanding the reasons for the immediate post-transplant increase in month 1. There is no influence on the sex of the renal recipient nor on the type of donor. Only the age in recipients older than 50 years has a ratio of higher triglyceride values in months 9 and 12 and in cholesterol in the 12 months post-transplant.

Factors That Influence the Attitude of the Population to Be a Donor in Mexico.

BACKGROUND: Transplantation depends on a donation from a living or deceased donor, with the latter ideally involving a multiorgan transplant. The objective of this study was to determine the factors that influence the attitudes of the population in Mexico toward being a donor. METHODS: We conducted an observational, cross-sectional study with a survey on the attitudes toward donation in the population of Mexico. The survey had 33 items on it regarding sociodemographic aspects and people's positions on the issues of organ and tissue donation. We used central tendency and dispersion averages and calculated the difference between groups using chi squares or the Student t test. We also used the statistical program SPSS version 25. RESULTS: The perception of respondents regarding organ and tissue donation (with 1064 people or 65.1% in favor) points to a lack of knowledge in Mexico. People do not talk about organ donation with their relatives and especially do not discuss their wishes in case of death (only 660 people indicated they had or 40.4%). There is a better attitude toward donation among younger respondents, women, single people, health personnel, people with higher incomes, Catholics, and those who do not have a hospitalized family member. CONCLUSIONS: It is necessary to provide more information about organ donation to people in Mexico. The opinion toward donation is generally favorable; however, there are multiple factors that influence opinions. Family members of patients in intensive care are the least willing to donate themselves or donate a relative's organs.