Follistatin-like 1 (FSTL1) levels as potential early biomarker of cardiovascular disease in a Mexican population.

Cardiovascular diseases (CVD) are the leading cause of death globally. In recent years, follistatin-like protein 1 (FSTL1) has been proposed as an emerging potential clinical biomarker of CVD, since its concentration is upregulated in heart failure. The aim of the present study was to evaluate the association of FSTL1 levels and classic biomarkers with the risk of CVD in Mexican population. A case-control study was carried out in patients with cardiovascular diseases (CVD), arterial hypertension, but not CVD (cardiovascular risk factor-CRF), and healthy controls (control group) from the Mexican Institute of Social Security. Lipid profile, homocysteine (Hcys), serum amyloid A (SAA), FSTL1 concentration, PON1 concentration and activities [Arylesterase (ARE), and Lactonase (LAC)] were evaluated. High levels of FSTL1 were found in the CRF group and a positive association of FSTL1 (OR = 4.55; 95% CI 1.29-16.04, p = 0.02) with the presence of arterial hypertension, as well as Hcys (OR, 3.09; 95% CI 1.23-7.76, p = 0.02) and SAA (OR, 1.03; 95% CI 1.01-1.05, p < 0.01) with the presence of CVD. LAC activity (OR, 0.26; 95% CI 0.07-0.94, p = 0.04) and PON1 concentration (OR, 0.17; 95% CI 0.05-0.62, p = 0.01) were associated with a decrease in OR belonging to the group with CVD. Our results suggest that FSTL1 may be a useful biomarker for monitoring cardiovascular risk in clinical settings. However, longitudinal studies are needed to evaluate how FSTL1 could influence the association of PON1 activity and Hcys with CVD.

Kidney Transplantation during the First Year of COVID-19 Pandemic in Our Center

Introduction: SARS-CoV2 pandemic has altered the normal activity in our day-to-day life. During the most critical moments of the pandemic at the hospital, attendance and programmed activities had to be reduced to a minimum, including kidney transplants. Hospitals with this kind of activity had to suspend or restructure it due to the decrease in the number of donors with a solid organ donation profile, the lack of knowledge as to whether the disease could be transmitted through transplantation or the risk that was believed to be associated with the admission of patients with end-stage chronic kidney disease or immunosuppressive treatment. Methods: A retrospective review of all patients who had received a kidney transplant at Doctor Peset University Hospital in Valencia was performed from March 2020 to March 2021. The objective was to study the safety of kidney transplantation and the incidence of COVID-19 disease in kidney transplant patients during this pandemic period. Results: 56 cases of kidney transplantation were included, most of them male with an average age of 56 years old, and variable comorbidity such as hypertension, dyslipidemia, an average body mass index of 26 and undergoing renal replacement therapy by hemodialysis. Regarding the organ donors, more than 50% were male patients and the donation was in encephalic death. The average cold ischemia time was 15 hours. Postoperative complications were mostly graded I and II in the Clavien-Dindo classification. 5.4% of the recipients had passed the SARS-CoV2 infection prior to the transplant and 5.4% were infected with COVID-19 after the transplant. Conclusion: In our experience, the current kidney transplant program seems viable and safe, even during periods of health emergencies (AU)

Introducción: La pandemia por SARS-CoV2 ha alterado la actividad habitual en nuestro día a día. Durante losmomentos más críticos de la pandemia a nivel hospitalariose tuvieron que reducir al mínimo la presencialidad y la actividad programada, incluyendo dentro de ésta el trasplanterenal. Los hospitales con dicha actividad tuvieron que suspenderla o bien reestructurarla debido a la disminución en elnúmero de donantes con perfil para la donación de órganossólidos, al desconocimiento de si la enfermedad podía transmitirse a través del trasplante o al riesgo que se creía quepodría conllevar ingresar pacientes con enfermedad renalcrónica terminal o en tratamiento inmunosupresor.Métodos: Se realizó una revisión retrospectiva de lospacientes que recibieron un trasplante renal en el Hospital Universitario Doctor Peset de Valencia desde marzo de2020 hasta marzo de 2021 con el objetivo de estudiar la seguridad del trasplante renal y la incidencia de enfermedadpor COVID-19 en los pacientes trasplantados renales durante este periodo de pandemia.Resultados: Se incluyeron 56 casos de trasplante renal, la mayor parte de ellos de sexo masculino, con una edadmedia de 56 años, un índice de masa corporal medio de 26 yen tratamiento renal sustitutivo mayoritariamente mediantehemodiálisis (50%). Con respecto a los donantes, más del50% eran de sexo masculino y la donación fue en muerteencefálica. El tiempo medio de isquemia fría fue de 15 horas. Las complicaciones posquirúrgicas fueron en su mayoría de grado I y II en la clasificación de Clavien-Dindo.Un 5.4% de los receptores habían pasado la infección porSARS-CoV2 previamente al trasplante y un 5.4% se infectaron por COVID-19 posteriormente al trasplante.Conclusión: En nuestra experiencia, parece viable yseguro el programa de trasplante renal vigente, incluso durante periodos de emergencia sanitaria. (AU)

Results from the INMUNOSUN-SOGUG trial: a prospective phase II study of sunitinib as a second-line therapy in patients with metastatic renal cell carcinoma after immune checkpoint-based combination therapy.

BACKGROUND: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. PATIENTS AND METHODS: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. RESULTS: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. CONCLUSION: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens.

20 años de experiencia en trasplante renal en bloque de donantes pediátricos en receptores adultos / A 20-year experience in cadaveric pediatric en bloc kidney transplantation in adult recipients

Introducción y objetivos El trasplante renal en bloque de donantes pediátricos en receptores adultos permite aumentar el pool de donantes, pero son pocos los centros que lo realizan. Mostramos los resultados de la técnica en nuestro centro tras su introducción en el año 1999.Material y métodos Análisis retrospectivo de los 42 procedimientos realizados en nuestro centro con una mediana de seguimiento de 73 meses (5-233) en los que se monitorizó la función renal de los pacientes y se registraron las complicaciones sucedidas.Resultados Se han realizado 42 trasplantes renales en bloque en adultos de donantes pediátricos en nuestro centro hasta el momento. La media de edad de los receptores fue de 44,1±11,8 años y la de los donantes de 22,4±14,7 meses, con un peso medio de 11,3±3,6kg. El tiempo medio de isquemia fría fue de 15,7±4,5 h. Al finalizar el seguimiento, 35 injertos eran funcionantes (83,3%) y mantenían una excelente función. Hubo 7 pérdidas de injerto (16,7%) en el postoperatorio inmediato (4 trombosis vasculares, una dehiscencia de anastomosis y 2necrosis corticales) y un fallecimiento durante el seguimiento por una causa no relacionada.Conclusiones El uso de injertos renales en bloque de origen pediátrico en adultos es un procedimiento seguro y con un excelente rendimiento funcional a medio y largo plazo. El postoperatorio inmediato es el periodo en el que se establecen la mayoría de las complicaciones importantes que pueden derivar en la pérdida del injerto. La adecuada selección de donantes y receptores, así como una correcta técnica quirúrgica, son imprescindibles para minimizar la aparición de eventos adversos (AU)

Background En bloc kidney transplantation from pediatric donors into adult recipients increases the donor pool. However, this surgical procedure is not widely performed in many transplant centers. To evaluate the long-term outcomes of bloc kidney transplantation from pediatric donors into adult recipients in a single center.Material and methods Retrospective analysis of 42 patients who received pediatric cadaveric bloc kidney transplantation in our center since 1999. Median follow-up period was 73 months (5-233) in which renal function tests were taken and complications registered.ResultsWe have performed 42 bloc kidney transplantation from pediatric donors into adult recipients in our center. The recipients’ age was 44.1±11.8 years. Pediatric donors were 22.4±14.7 months old and weighted 11.3±3.6kg. Cold ischemia time was 15.7±4.5hours. During a median follow-up of 73 months, 35 patients (83.3%) had graft survival with excellent function (first-year serum creatinine levels of 0.99±0.25mg/dl). There were 7graft losses (16.7%) in the immediate postoperative period (4 cases of vascular thrombosis, one anastomosis dehiscence and 2cortical necrosis).Conclusions The pediatric en bloc renal graft transplantation into adults is a safe technique with excellent medium- to long-term functional performance. The vast majority of significant complications leading to graft loss were reported in the immediate postoperative period. A good selection of donors and recipients as well as an adequate surgical technique are essential to minimize the occurrence of adverse events (AU)

A 20-year experience in cadaveric pediatric en bloc kidney transplantation in adult recipients.

BACKGROUND AND OBJECTIVES: En bloc kidney transplantation (EBKT) from pediatric donors into adult recipients increases the donor pool. However, this surgical procedure is not widely performed in many transplant centers. To evaluate the long-term outcomes of EBKT from pediatric donors into adult recipients in a single center. MATERIAL AND METHODS: Retrospective analysis of 42 patients who received pediatric cadaveric EBKT in our center since 1999. Median follow-up period was 73 months (5-233) in which renal function tests were taken and complications registered. RESULTS: We have performed 42 EBKT from pediatric donors into adult recipients in our center. The recipients' age was 44.1 ± 11.8 years. Pediatric donors were 22.4 ± 14.7 months old and weighted 11.3 ± 3.6 kg. Cold ischemia time was 15.7 ± 4.5 h. During a median follow-up of 73 months, 35 patients (83.3%) had graft survival with excellent function (first-year serum creatinine levels of 0.99 ± 0.25 mg/dl). There were seven graft losses (16.7%) in the immediate postoperative period (four cases of vascular thrombosis, one anastomosis dehiscence and two cortical necrosis). CONCLUSIONS: The pediatric en bloc renal graft transplantation into adults is a safe technique with excellent medium- to long-term functional performance. The vast majority of significant complications leading to graft loss were reported in the immediate postoperative period. A good selection of donors and recipients as well as an adequate surgical technique are essential to minimize the occurrence of adverse events.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues (AU)

Small ruminant SexedULTRA™ sperm sex-sorting: Status report and recent developments.

Flow cytometry sperm sex-sorting based on the relative DNA difference between X- and Y-chromosome bearing populations is an established method that has allowed the production of pre-sexed offspring in a multitude of species and has been a commercial success in cattle production for the past twenty years. Several improvements to the technology and the processing methods have increased the sorting efficiency of ejaculates and the post-thaw quality of sex-sorted sperm, allowing for the fertility gap between conventional (non-sorted) and SexedULTRA™ sex-sorted sperm to be bridged. Small ruminant industries are now progressively testing sex-sorted sperm for application in their specific niches and environments. A review of the key advances and the recent developments in caprine, ovine and cervine sperm sex-sorting technology are described in this publication.

A multidisciplinary consensus on the morphological and functional responses to immunotherapy treatment.

The implementation of immunotherapy has radically changed the treatment of oncological patients. Currently, immunotherapy is indicated in the treatment of patients with head and neck tumors, melanoma, lung cancer, bladder tumors, colon cancer, cervical cancer, breast cancer, Merkel cell carcinoma, liver cancer, leukemia and lymphomas. However, its efficacy is restricted to a limited number of cases. The challenge is, therefore, to identify which subset of patients would benefit from immunotherapy. To this end, the establishment of immunotherapy response criteria and predictive and prognostic biomarkers is of paramount interest. In this report, a group of experts of the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Medical Radiology (SERAM), and Spanish Society of Nuclear Medicine and Molecular Imaging (SEMNIM) provide an up-to-date review and a consensus guide on these issues.

Optimization of a 5-day fixed-time embryo transfer (FTET) protocol in heifers I. Manipulation of circulating progesterone through reutilization of intravaginal progesterone devices during FTET.

The objectives of the present study were to: 1) compare the reproductive efficiency of embryo transfer (ET) recipients after synchronization of estrus or a 5-day synchronization of ovulation protocol for fixed time ET (FTET), and 2) determine the effect of reutilization of intravaginal P4 devices (CIDRs), up to four times, in a 5-day FTET protocol. In Experiment 1, 817 dairy heifers were assigned to one of three groups: PGF + estrus detection, 5-d FTET protocol with new (1.38 g P4) or 2nd use CIDR (previously used once for 5 d). Fresh in vitro produced embryos were transferred 7 ± 1 day after estrus (PGF + estrus) or GnRH (5-day FTET). Utilization rate (transferred/treated) was greater (P < 0.001) in heifers submitted to FTET compared to ET after estrus, however pregnancies per ET (P/ET) were not different (P > 0.10). As a result, pregnancy per treated (P/treated) recipient was greater (P < 0.05) in heifers in the 5-day FTET protocol. In Experiment 2, 40 dairy heifers without a corpus luteum (CL) were randomly allocated into one of four groups using new, 2nd use, 3rd use (previously used twice for 5 d/each), or 4th use (previously used thrice for 5 d/each) CIDRs. Circulating P4 was reduced (P < 0.01) with each reutilization. In Experiment 3, ovarian follicular dynamics were evaluated in 238 dairy heifers submitted to a 5-day protocol with either new, 2nd use, 3rd use or 4th use CIDRs at random stages of the estrous cycle. Prostaglandin F2α (PGF) was administered at CIDR removal and again 24 h later. Ovulation was induced by GnRH treatment 72 h after CIDR removal. Preovulatory follicle diameter increased (P < 0.001) progressively with increasing CIDR reutilization. Ovulation rate did not differ between treatments, however, interval from CIDR removal to ovulation decreased (P < 0.001) in heifers receiving 3rd and 4th use CIDRs compared to new or 2nd use. Finally, in Experiments 4 and 5, 1203 heifers submitted to a 5-day FTET protocol were randomly assigned to receive either a new CIDR, a 3rd use CIDR (Experiment 4) or a 4th use CIDR (Experiment 5). Despite the increase in CL volume on D5 in heifers treated with 3rd use (P = 0.03) or 4th use CIDRs (P < 0.01), there were no differences (P > 0.05) in utilization rate, P/ET, or P/treated. Thus, use of a 5-day FTET synchronization protocol improves reproductive efficiency by increasing recipient utilization, and reutilization of CIDRs up to four times in recipient dairy heifers does not compromise reproductive performance.

Mexican population sub-analysis of the lixilan clinical program with the fixed ratio combination of insulin glargine and lixisenatide (iGlarLixi).

AIM: To evaluate the efficacy and safety of iGlarLixi in Mexican patients with type 2 diabetes who participated in the LixiLan clinical trials and compare results with the rest of the patients. METHODS: Data was collected for Mexican patients who participated in either of three studies: phase 2 trial LixiLan-POC, that compared iGlarLixi vs insulin glargine (iGlar) on inadequately controlled patients with metformin; phase 3 trial LixiLan-O, comparing iGlarLixi vs iGlar and lixisenatide on inadequately controlled patients with oral antidiabetic agents; and finally the phase 3 trial LixiLan-L, comparing iGlarLixi vs iGlar on inadequately controlled patients with basal insulin. The primary endpoint was the change in HbA1c from baseline to end of treatment. RESULTS: In the Mexican population, treatment with iGlarLixi significantly improved HbA1c compared with each component alone achieving an average of 6.5%; (6.17%, 6.63% and 6.73% for the LixiLan-POC, O and L studies respectively) and an average HbA1c reduction from baseline of 1.6%, for the three studies at end of treatment period. CONCLUSION: The efficacy and safety profile of iGlarLixi demonstrate a fair or better composite endpoint of HbA1c without hypoglycemia and no weight gain compared to overall trial population, which could help improve Mexican patients' outcomes.

[Clinical and socio-demographic profile of neurosyphilis: a retrospective study in a reference centre in Colombia]. / Perfil clinico y sociodemografico de la neurosifilis: estudio retrospectivo en un centro de referencia de Colombia.

INTRODUCTION: Neurosyphilis is the Treponema pallidum infection of the central nervous system and can occur at any time after the initial infection. In the 21st century, the incidence of neurosyphilis has increased in the post-antibiotic era. The highest rates of neurosyphilis are from low-income countries and the published studies are limited. AIM: To determine the clinical and sociodemographic characteristics of neurosyphilis patients in a tertiary care center in Pereira, Colombia. PATIENTS AND METHODS: Retrospective study of diagnosed neurosyphilis patients in a tertiary care center in Pereira, Colombia, between 2012 to 2017. The diagnosis was established based on serologic treponemal tests, VDRL in CSF, and CSF analysis. Sociodemographic, clinical, and laboratory parameters variables were obtained. RESULTS: Sixteen patients were included, 11 with definitive neurosyphilis and 5 with probable neurosyphilis. The median age was 59.50 ± 13.78 years. Men accounted for 75% (n = 12) of the patients. Four patients were (25%) HIV-infected. All the patients had positive peripheral FTA-ABS and 11 had reactive VDRL in CSF. The most frequent form was late neurosyphilis (62.5%), being general paralysis the most common. The most frequently clinical manifestations were neuropsychiatric alterations (46.9%), predominantly disorientation, behavioral changes, and cognitive impairment, followed by motor changes (36.7%). CONCLUSIONS: Late neurosyphilis was the most prevalent form, predominantly neuropsychiatric alterations. Only a quarter of patients presented HIV coinfection.

TITLE: Perfil clinico y sociodemografico de la neurosifilis: estudio retrospectivo en un centro de referencia de Colombia.Introduccion. La neurosifilis es causada por Treponema pallidum y puede afectar al sistema nervioso central en cualquier momento de la infeccion. Desde inicios de este siglo, su incidencia ha ido en aumento, aun en la era postantibiotica. En paises en vias de desarrollo, el problema tiene mayor magnitud y los estudios son escasos. Objetivo. Describir las caracteristicas de la poblacion con neurosifilis en un hospital de tercer nivel de Pereira, Colombia. Pacientes y metodos. Estudio descriptivo de corte transversal de pacientes con neurosifilis que acudieron a un centro de tercer nivel de Pereira, Colombia, entre 2012 y 2017. Los criterios diagnosticos se basaron en las siguientes variables: prueba treponemica en sangre, VDRL y analisis citoquimico del liquido cefalorraquideo. Se consideraron variables sociodemograficas, clinicas y de laboratorio. Resultados. Se incluyo a 16 pacientes, 11 con neurosifilis definitiva y cinco con neurosifilis probable, con una edad media de 59,5 ± 13,78 años. El 75% (n = 12) de los casos eran hombres. La coinfeccion por virus de la inmunodeficiencia humana fue del 25%. Todos los pacientes tenian FTA-ABS positivo en sangre y 11 presentaron VDRL reactiva en el liquido cefalorraquideo. La forma mas frecuente de neurosifilis fue la tardia (62,5%), y predomino la paralisis general. Las manifestaciones clinicas mas frecuentes fueron las alteraciones neuropsiquiatricas (46,9%), con predominio de la desorientacion, los cambios en el comportamiento y el deterioro cognitivo, seguidos de las alteraciones motoras (36,7%). Conclusiones. La neurosifilis tardia fue la presentacion mas prevalente, caracterizada por manifestaciones neuropsiquiatricas. Una cuarta parte de los pacientes presentaba infeccion por virus de la inmunodeficiencia humana.

Clinical and sociodemographic profile of epilepsy in adults from a reference centre in Colombia. / Perfil clínico y sociodemográfico de la epilepsia en adultos de un centro de referencia de Colombia.

OBJECTIVES: To describe the sociodemographic and clinical characteristics of a cohort of patients with epilepsy from a reference centre in Colombia. METHODS: Cross-sectional study including patients diagnosed with epilepsy who attended our epilepsy centre (Neurocentro) between 2013 and 2016. Data were gathered from patients' medical histories. RESULTS: We gathered data from a total of 354 patients diagnosed with epilepsy. Median age was 37 years; 52% were men. Seizures were focal in 57% of the patients and generalised in 38%; seizure type was not determined in 6% of the sample. The most frequent aetiology was cryptogenic (21%), followed by traumatic (14%). Median time of disease progression and age at onset were 23 and 11 years, respectively. Psychiatric comorbidities were found in 18% of the patients and 40% had some degree of cognitive impairment. Around 40% of our sample reported adverse reactions to antiepileptic drugs at some point during treatment. Antiepileptic drugs were administered in monotherapy in 36% of the patients. Around 37% had drug-resistant epilepsy and 14% underwent surgery. CONCLUSIONS: Psychiatric comorbidities, cognitive impairment, adverse drug reactions, and drug-resistant epilepsy are common among epileptic patients in Colombia. Knowledge of the factors with an impact on epilepsy may lay the foundations for improving management of these patients on the administrative level and improving quality of life.

Review: Semen sexing - current state of the art with emphasis on bovine species.

It is approaching three decades since the first public evidence of sex-sorting of semen. The technology has progressed considerably since then with a number of institutions and researchers collaborating to eventually bring this to application. The technical challenges have been quite substantial and in the early years the application was limited to only heifer inseminations. Comparable fertility of sex-sorted semen with conventional semen has been an aspirational benchmark for the industry for many years. Significant investment in research in the primary biology of sex-sorted sperm and associated sorting equipment ensured steady progress over the years and current methods particularly the new SexedULTRA-4M™ seems to have now mostly bridged this fertility gap. The dairy and beef industry have adopted this technology quite rapidly. Other animal industries are progressively testing it for application in their specific niches and environments. The current state of the art in the fundamentals of sex-sorting, the biology of the process as well as new developments in machinery are described in this review.