Caracterización de pacientes con enfermedades asociadas a inmunosupresión con infecciones por Cryptosporidium spp. atendidos en un hospital pediátrico referencial de Argentina, 2018-2023 / Description of the characteristics of patients with diseases associated with immunosuppression and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina, 2018­2023

Cryptosporidium spp. es un protozoario productor de diarrea. Los pacientes inmunocomprometidos pueden desarrollar formas clínicas graves y persistentes. Se describen las características de pacientes con enfermedad de base asociada a inmunosupresión (EAI) con infección por Cryptosporidium spp. (IC) atendidos en un hospital pediátrico referencial de Argentina entre los años 2018 y 2023. Se analizaron datos demográficos, EAI, características de la diarrea y coinfecciones. Se incluyeron 30 pacientes con EAI e IC. La mayoría registró trasplante de órgano sólido, neoplasia hematológica e inmunodeficiencia primaria. Dieciocho presentaron diarrea persistente al momento del diagnóstico. Seis pacientes registraron coinfecciones. Se debe considerar la criptosporidiosis en el diagnóstico diferencial de enfermedad diarreica aguda o persistente en niños con distintos tipos de EAI, como el trasplante de órgano sólido, neoplasias hematológicas e inmunodeficiencias primarias.

Cryptosporidium spp. is a diarrhea-causing protozoan. Immunocompromised patients may develop severe and persistent clinical forms. Here we describe the characteristics of patients with an underlying disease associated with immunosuppression (DAI) and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina between 2018 and 2023. Demographic data, DAI, diarrhea characteristics, and co-infections were analyzed. A total of 30 patients with DAI and cryptosporidiosis were included. Most of them had undergone a solid organ transplant, had a hematologic neoplasm, or primary immunodeficiency. Persistent diarrhea was observed in 18 patients at the time of diagnosis. Co-infections were recorded in 6 patients. Cryptosporidiosis should be considered in the differential diagnosis of acute or persistent diarrhea in children with different types of DAI, such as solid organ transplant, hematologic neoplasms, and primary immunodeficiencies.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.

Description of the characteristics of patients with diseases associated with immunosuppression and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina, 2018-2023. / Caracterización de pacientes con enfermedades asociadas a inmunosupresión con infecciones por Cryptosporidium spp. atendidos en un hospital pediátrico referencial de Argentina, 2018-2023.

Cryptosporidium spp. is a diarrhea-causing protozoan. Immunocompromised patients may develop severe and persistent clinical forms. Here we describe the characteristics of patients with an underlying disease associated with immunosuppression (DAI) and Cryptosporidium spp. infection seen at a referral children's hospital in Argentina between 2018 and 2023. Demographic data, DAI, diarrhea characteristics, and co-infections were analyzed. A total of 30 patients with DAI and cryptosporidiosis were included. Most of them had undergone a solid organ transplant, had a hematologic neoplasm, or primary immunodeficiency. Persistent diarrhea was observed in 18 patients at the time of diagnosis. Co-infections were recorded in 6 patients. Cryptosporidiosis should be considered in the differential diagnosis of acute or persistent diarrhea in children with different types of DAI, such as solid organ transplant, hematologic neoplasms, and primary immunodeficiencies.

Cryptosporidium spp. es un protozoario productor de diarrea. Los pacientes inmunocomprometidos pueden desarrollar formas clínicas graves y persistentes. Se describen las características de pacientes con enfermedad de base asociada a inmunosupresión (EAI) con infección por Cryptosporidium spp. (IC) atendidos en un hospital pediátrico referencial de Argentina entre los años 2018 y 2023. Se analizaron datos demográficos, EAI, características de la diarrea y coinfecciones. Se incluyeron 30 pacientes con EAI e IC. La mayoría registró trasplante de órgano sólido, neoplasia hematológica e inmunodeficiencia primaria. Dieciocho presentaron diarrea persistente al momento del diagnóstico. Seis pacientes registraron coinfecciones. Se debe considerar la criptosporidiosis en el diagnóstico diferencial de enfermedad diarreica aguda o persistente en niños con distintos tipos de EAI, como el trasplante de órgano sólido, neoplasias hematológicas e inmunodeficiencias primarias.

Bioética en donantes en asistolia controlada / Bioethics in controlled asystole donor / Bioética no doador em assistolia controlada

Las campañas de prevención y promoción de salud, así como los avances en las medidas terapéuticas destinadas a los pacientes neurocríticos, han logrado reducir la incidencia de pacientes con injuria encefálica aguda (IEA) que evolucionan a la muerte encefálica (ME). Sin embargo, en la mayoría de los países de América Latina, los órganos perfusibles aptos para trasplante (TX) provienen de donantes fallecidos en ME. La donación en asistolia (DA), y en particular la donación en asistolia controlada (DAC), constituye una opción aceptada y válida para la obtención de órganos que contribuiría a la disminución de las listas de espera para trasplante. Durante el proceso de DAC, se aplican conceptos con fuerte impronta bioética cuya aplicación resulta fundamental en el momento de la toma de decisiones. El presente artículo tiene el objetivo de analizar dichos conceptos con la finalidad de otorgar herramientas válidas al equipo asistencial para aquellos procesos en los que existe deliberación moral, como ocurre en la donación de órganos en asistolia controlada, considerada parte integral de los cuidados al final de la vida.

Campaigns for health prevention and promotion, along with advancements in therapeutic measures for neurocritical patients, have succeeded in reducing the incidence of patients with acute brain injury (ABI) progressing to brain death (BD). However, in most Latin American countries, suitable perfusable organs for transplantation (TX) come from deceased donors in brain death (BD). Donation after circulatory death (DCD), particularly controlled donation after circulatory death (cDCD), represents an accepted and valid option for organ procurement that would contribute to reducing transplant waiting lists. During the cDCD process, strong bioethical principles are applied, and their implementation is crucial when making decisions. The purpose of this article is to analyze these concepts, aiming to provide valid tools to the healthcare team for processes involving moral deliberation, such as controlled circulatory death organ donation, considered an integral part of end-of-life care.

As campanhas de prevenção e promoção da saúde, bem como os avanços na medidas terapêuticas voltadas para pacientes neurocríticos conseguiram reduzir a incidência de pacientes com lesão cerebral aguda que evoluem para morte encefálica (ME). No entanto, na maioria dos países latino-americanos, os órgãos que podem ser perfundidos adequados para transplante (TX) vêm de doadores falecidos em ME. A doação em assistolia e em particular a doação em assistolia controlada (DAC),é uma opção aceita e válida para a obtenção de órgãos, o que contribuiria para a redução das listas de espera para transplantes. Durante o processo DAC, são aplicados conceitos com forte cunho bioético, que são fundamentais na o momento da tomada de decisão. Este artigo tem como objetivo analisar esses conceitos, com o objetivo de oferecer ferramentas válidas à equipe de saúde, para os processos em que há deliberação moral como ocorre na doação de órgãos em assistolia controlada considerada parte integrante dos cuidados de fim de vida.

Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Impact of the COVID-19 Pandemic on Solid Organ Transplant and Rejection Episodes in Brazil's Unified Healthcare System.

BACKGROUND: Brazil has the world's largest public organ transplant program, which was severely affected by the COVID-19 pandemic. The primary aim of the study was to evaluate differences in solid organ transplants and rejection episodes during the COVID-19 pandemic compared to the five years before the pandemic in the country. METHODS: A seven-year database was built by downloading data from the DATASUS server. The pandemic period was defined as March 2020 to December 2021. The pre-pandemic period was from January 2015 to March 2020. RESULTS: During the pandemic, the number of solid organ transplants decreased by 19.3% in 2020 and 22.6% in 2021 compared to 2019. We found a decrease for each evaluated organ, which was more pronounced for lung, pancreas, and kidney transplants. The seasonal plot of rejection data indicated a high rejection rate between 2018 and 2021. There was also an 18% (IRR 1.18 (95% CI 1.01 to 1.37), p = 0.04) increase in the rejection rate during the COVID-19 pandemic. CONCLUSIONS: The total number of organ transplants performed in 2021 represents a setback of six years. Transplant procedures were concentrated in the Southeast region of the country, and a higher proportion of rejections occurred during the pandemic. Together, these findings could have an impact on transplant procedures and outcomes in Brazil.

Brazilian perspective: antimicrobial stewardship in solid organ transplant.

BACKGROUND: The incidence of multidrug resistant organisms (MDROs) infections among solid organ transplant (SOT) patients is very high in Brazil. METHODS: This review will discuss antimicrobial use and resistance in SOT in Brazil, highlighting the main barriers and facilitators for implementation of an antimicrobial stewardship programme (ASP). RESULTS: The most common group of MDROs is carbapenem-resistant Gram-negative bacteria and vancomycin-resistant Enterococcus. Carbapenem-resistant Enterobacterales (CREs) are the most frequent MDROs and have been reported as donor-derived as well. Although ASPs are mandatory in the country, there is a lack of information regarding ASPs in SOT recipients. The main barriers for the implementation of ASPs in Brazilian hospitals are lack of electronic medical records, absence of national guidelines specific to SOT recipients, lack of recommendations on surveillance culture to evaluate colonization and transmission of donor-derived MDROs, limited availability of rapid diagnostic tests, and insufficient pharmacist and clinician time allocated to ASP activities in some SOT centers. CONCLUSIONS: The incidence of MDRO infections caused mainly by VREs and CREs is very high in the country. There is limited data regarding antimicrobial use among SOT recipients in Brazil. The absence of antimicrobial stewardship national guidelines specific to SOT recipients is one of the main barriers for the implementation of ASPs in Brazilian hospitals.

SARS-CoV-2 vaccine booster in solid organ transplant recipients previously immunised with inactivated versus mRNA vaccines: A prospective cohort study.

Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.

Liver transplant after SARS-CoV-2 infection: A systematic review.

BACKGROUND: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. METHODS: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were "COVID-19" and "Liver transplantation". RESULTS: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5‒44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. CONCLUSION: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790).

Immune Response to COVID-19 and mRNA Vaccination in Immunocompromised Individuals: A Narrative Review.

Immunocompromised individuals are at high risk of poor coronavirus disease 2019 (COVID-19) outcomes and demonstrate a lower immune response to COVID-19 vaccines, including to the novel mRNA vaccines that have been shown to elicit high neutralizing antibody levels. This review synthesized available data on the immune response to COVID-19 and critically assessed mRNA COVID-19 vaccine immunogenicity in this vulnerable subpopulation. Patients with various immunocompromising conditions exhibit diverse responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity and mortality, and available vaccines elicit lower immune responses, particularly in solid organ transplant recipients. Strategies to improve vaccine responses in immunocompromised individuals are being implemented in vaccine recommendations, including the use of a third and fourth vaccine dose beyond the two-dose series. Additional doses may enhance vaccine effectiveness and help provide broad coverage against emerging SARS-CoV-2 variants. Continued investigation of vaccines and dosing regimens will help refine approaches to help protect this vulnerable subpopulation from COVID-19.

Role of fibrinogen in the attenuation of ischemia reperfusion and remote ischemic preconditioning / El papel del fibrinógeno en la atenuación de la isquemia-reperfusión y el preacondicionamiento isquémico remoto

Abstract Background: Ischemic reperfusion injury (IRI) is a common hazard involved in many human diseases, such as cerebral stroke, myocardial infarction, solid organ transplant dysfunction or failure, and vascular diseases. Understanding the molecular bases of this injury is essential for the prevention and control of these life-threatening conditions. Ischemic and remote ischemic preconditioning techniques (IPC and RIPC, respectively) have gained increasing importance in the clinical practice to protect against the IRI; however, the exact mechanisms of these techniques are not fully understood, which renders their clinical application query. Possible effectors: Nitric oxide (NO) has been reported by multiple studies to be an important mediator of the protective effects of those techniques. While the physiological concentrations of NO and fibrinogen (FB) are known to antagonize each other, the circulating levels of both effectors increase in response to RIPC. Hypothesis: While NO has potential anti-inflammatory effects, non-soluble fibrinogen (sFB) shows pro- inflammatory effects. However, the sFB may have the potential to act synergistically rather than antagonistically with NO toward the attenuation of the IRI. Conclusion: While increased FB is considered a risk factor for cardiovascular and inflammatory conditions that is also able to decrease the efflux of NO, and increase the NO oxidative metabolits and S- nitroglutathione, the increased sFB during the acute phase reaction might have other protective aspects that should be carefully investigated.

Resumen Antecedentes: La lesión por isquemia-reperfusión (LIR) es un riesgo común involucrado en muchas enfermedades humanas tales como derrame cerebral, infarto del miocardio, disfunción o falla de trasplante de órgano sólido, y enfermedades vasculares. Una comprensión de la base molecular de esta lesión es fundamental para la prevención y el control de estas enfermedades potencialmente mortales. Las técnicas de preacondicionamiento isquémico y preacondicionamiento isquémico remoto (PIR) han cobrado una creciente importancia en la práctica clínica para la protección contra la LIR, sin embargo, los mecanismos precisos de estas técnicas no se entienden plenamente, lo cual pone en duda su aplicación clínica. Posibles efectores: El óxido nítrico (ON) ha sido reportado por varios estudios como un importante mediador de los efectos protectores de estas técnicas. Si bien se sabe que las concentraciones fisiológicas del ON y fibrinógeno son antagónicas, los niveles circulantes de ambos efectores aumentan en respuesta al PIR. Hipótesis: Aunque el ON tiene posibles efectos anti-inflamatorios, el fibrinógeno insoluble muestra efectos proinflamatorios. Sin embargo, el fibrinógeno soluble puede tener el potencial de actuar de manera sinérgica en lugar de antagónica con el ON hacia la atenuación de la LIR. Conclusión: Aunque el fibrinógeno elevado se considera un factor de riesgo para las enfermedades cardiovasculares e inflamatorias, que también puede disminuir la descarga de ON y aumentar los niveles de metabolitos oxidantes del ON y de S-nitrosoglutatión, el aumento de fibrinógeno soluble durante la reacción de fase aguda puede tener otros aspectos protectores que deben ser cuidadosamente investigados.

HLA-G y su función en trasplantes de órganos sólidos / HLA-G and its role in solid organ transplants

RESUMEN El trasplante de órganos sólidos se ha considerado el fin último para algunas enfermedades crónicas en estadio terminal, sin embargo, las incompatibilidades del HLA entre el donante y el receptor pueden permitir que la alorespuesta se convierta en nociva para el órgano trasplantado, respuesta que puede ser tanto innata como adaptativa. Se ha identificado el HLA-G como una molécula natural inductora de tolerancia (28) principalmente en el embarazo y se considera una molécula del HLA clase I no clásico, sin embargo, comparte algunas características estructurales con el HLA clásico. Los genes HLA-G se caracterizan por tener un limitado polimorfismo y una distribución celular y tisular restringida al trofoblasto fetal y células del epitelio tímico entre otras. La búsqueda persistente de la tolerancia en los trasplantes de órganos ha permitido un estudio específico del HLA-G, como posibilidad terapéutica para aumentar la sobrevida tanto de los injertos como de los pacientes trasplantados, es por tal motivo que se realiza una revisión en dicha molécula para estimular la investigación y entendimiento de sus funciones.

ABSTRACT Solid organ transplantation has been considered the ultimate goal for some end-stage chronic diseases, however, HLA incompatibilities between the donor and the recipient may allow the alloresponse to become deleterious for the transplanted organ, a response that can be both innate and adaptive. HLA-G has been identified as a natural tolerance-inducing molecule (28) mainly in pregnancy and is considered a non-classical HLA class I molecule; however, it shares some structural characteristics with classic HLA. HLA-G genes are characterized by having a limited polymorphism and a cellular and tissue distribution restricted to the fetal trophoblast and thymic epithelial cells, among others. The persistent search for tolerance in organ transplants has allowed a specific study of HLA-G, as a therapeutic possibility to increase grafts and transplant patient's survival; for this reason we carried out a review ofthis molecule to stimulate research and understanding of its functions.

Liver transplant after SARS-CoV-2 infection: A systematic review

Abstract Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were "COVID-19" and "Liver transplantation". Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5-44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)

Emerging and reemerging forms of Trypanosoma cruzi transmission

This review aims to update and discuss the main challenges in controlling emergent and reemergent forms of Trypanosoma cruzi transmission through organ transplantation, blood products and vertical transmission in endemic and non-endemic areas as well as emergent forms of transmission in endemic countries through contaminated food, currently representing the major cause of acute illness in several countries. As a neglected tropical disease potentially controllable with a major impact on morbimortality and socioeconomic aspects, Chagas disease (CD) was approved at the WHO global plan to interrupt four transmission routes by 2030 (vector/blood transfusion/organ transplant/congenital). Implementation of universal or target screening for CD are highly recommended in blood banks of non-endemic regions; in organ transplants donors in endemic/non-endemic areas as well as in women at risk from endemic areas (reproductive age women/pregnant women-respective babies). Moreover, main challenges for surveillance are the application of molecular methods for identification of infected babies, donor transmitted infection and of live parasites in the food. In addition, the systematic recording of acute/non-acute cases and transmission sources is crucial to establish databases for control and surveillance purposes. Remarkably, antiparasitic treatment of infected reproductive age women and infected babies is essential for the elimination of congenital CD by 2030.

Impact of COVID-19 on brain death and organ donation; a single center study in Turkey / Impacto del COVID-19 sobre la muerte cerebral y la donación de órganos; estudio de un centro en Turquía

ABSTRACT Objectives: More than 50 million people in the world have been diagnosed with COVID-19 and more than 1 million 250 thousand patients have died. With the increasing number of COVID-19 patients admitted to hospitals, problems related to non- COVID-19 patient care have emerged. Organ transplant organizations have had to adapt to this difficult time. The current and long- term impact due to the COVID-19 pandemic is an important factor to be taken into account. An important question to ask is how this outbreak has changed the organ donation process and how long it will take to address a potentially growing waiting list. Methods: We analized the effects of the pandemic COVID-19 in 2020 inTurkey between March and May. We have counted the number of brain deaths and organ donations in these months. We retrospectively compared the same months in 2019, the months before and after the pandemic in 2020, and the years 2019-2020. Results: When examined in other months, it is seen that the effect of the pandemic on brain death and organ donation continues not only in the months when the pandemic is intense, but also in other months. The total number of brain deaths in 2019 was 37, and family donations were 22; In 2020, the number of brain deaths decreased to 13, and family donations decreased to 7. This corresponds to a decrease of 64.86% and 68.18%, respectively, compared to the previous year. Conclusions: Brain death, organ onation and organ transplantation have decreased significantly with the onset of the pandemic compared to the previous years and the pre- pandemic period. Studies from different countries and regions have also shown that this decrease becomes even more pronounced where the number of cases is high.

RESUMEN Objetivos: Más de 50 millones de personas en el mundo han sido diagnosticadas con COVID-19 y más de 1 millón 250 mil pacientes han fallecido. Con el creciente número de pacientes con COVID-19 ingresados en hospitales, han surgido problemas relacionados con la atención de pacientes que no son de COVID-19. Las organizaciones de trasplantes de órganos han tenido que adaptarse a este momento difícil. El impacto actual y a largo plazo de la pandemia de COVID-19 es un factor importante a tener en cuenta. Una pregunta importante que debemos hacernos es cómo este brote ha cambiado el proceso de donación de órganos y cuánto tiempo llevará abordar una lista de espera potencialmente creciente. Material y métodos: Analizamos los efectos de la pandemia COVID-19 en 2020 en Turquía entre marzo y mayo. Hemos contado el número de muertes cerebrales y donaciones de órganos en estos meses. Comparamos retrospectivamente los mismos meses de 2019, los meses antes y después de la pandemia en 2020 y los años 2019-2020. Resultados: Cuando se examina en otros meses, se observa que el efecto de la pandemia sobre la muerte cerebral y la donación de órganos continúa no solo en los meses en que la pandemia es intensa, sino también en otros meses. El número total de muertes cerebrales en 2019 fue de 37 y las donaciones familiares fueron 22. En 2020, el número de muertes cerebrales disminuyó a 13 y las donaciones familiares disminuyeron a 7. Esto corresponde a una disminución del 64,86% y 68,18%, respectivamente, en comparación con el año anterior. Conclusiones: La muerte cerebral, la donación de órganos y el trasplante de órganos han disminuido significativamente con el inicio de la pandemia en comparación con los años anteriores y el período prepandémico. Los estudios de diferentes países y regiones también han demostrado que esta disminución se vuelve aún más pronunciada donde el número de casos es alto.

Serie de casos de trasplante hepático ortotópico del Hospital "Dr. Rafael Ángel Calderón Guardia" / Case series of liver transplantation in "Dr. Rafael Ángel Calderón Guardia Hospital"

Resumen Objetivo: Analizar los resultados y evolución del programa de trasplante hepático del Hospital "Dr. Rafael Ángel Calderón Guardia", así como las complicaciones más frecuentes y características de las hepatopatías que llevaron a trasplante hepático. Métodos: Esta es una investigación retrospectiva que involucra la revisión de expedientes clínicos de los pacientes que recibieron un trasplante de hígado entre los años 2009 y 2018 en el Hospital "Dr. Rafael Ángel Calderón Guardia" en San José, Costa Rica. Se consideraron las siguientes variables categóricas o discontinuas: edad, sexo, nacionalidad, lugar de procedencia, manifestaciones de la hepatopatía, motivo del trasplante, curso clínico postrasplante, comorbilidades, medicamentos empleados, complicaciones, resultados relevantes de exámenes de gabinete y biopsias. Los cálculos estadísticos se llevaron a cabo con paquetes estadísticos STATA, empleando como umbral de significancia estadística un valor de p menor de 0,05. Resultados: La muestra estuvo compuesta de un total de 45 cirugías de trasplante hepático y 44 pacientes que requirieron trasplante de hígado entre abril de 2009 y agosto de 2018, provenientes principalmente de la provincia de San José. El promedio de edad al momento del trasplante para la muestra total fue de 51 años. La hepatopatía que más frecuentemente llevó a trasplante fue la cirrosis etílica, seguida por esteatohepatitis no alcohólica y cirrosis criptogénica. Las complicaciones de la hepatopatía documentadas previo al trasplante: várices esofágicas, sangrado digestivo alto y síndrome hepatorenal. De los pacientes incluidos en el estudio fallecieron 10 en total, lo cual equivale a 22.7%. Conclusiones: La mortalidad observada en los casos de trasplante hepático analizados fue de 22,7%, la mayoría de los casos fueron llevados a trasplante por hepatopatía relacionada con cirrosis etílica, esteatohepatitis y cirrosis criptogénica.

Abstract Objective. To analyze the outcomes, most frequent complications and characteristics of the patients enrolled in the Liver Transplant Program from the Hospital "Dr. Rafael Ángel Calderón Guardia". Methods: This is a retrospective investigation that involves the revision of clinical records from the patients that received a liver transplant between the years 2009 and 2018 in the Hospital "Dr. Rafael Ángel Calderón Guardia". The following variables were considered: age, gender, nationality, city of residence, manifestations of the liver disease, reason for the liver transplant, clinical outcomes after transplant, comorbidities, medication received, important laboratory results and biopsies. The data analysis was performed with STATA, using a statistic significance threshold of a p < 0.05. Results: The sample was composed of a total of 45 liver transplant surgeries and 44 patients who received a liver transplant between the years 2009 and 2018. The patients mostly came from the city of San José. The average age at the time of the surgery was 51 years. The most common liver disease that led to transplant was alcoholic cirrhosis, followed by NASH and cryptogenic cirrhosis. The most common complications of the liver disease documented prior to transplant where esophageal varices, gastrointestinal bleeding and hepatic-renal syndrome. 10 of the patients included in the study died, which corresponds to 22.7% of the sample. Conclusions: The mortality observed in the liver transplant cases analyzed was 22.7%, most of the cases were taken to transplantation due to liver disease related to alcoholic cirrhosis, steatohepatitis and cryptogenic cirrhosis.

Outcomes of radiofrequency ablation for anal high-grade squamous intraepithelial lesions.

BACKGROUND: Radiofrequency ablation (RFA) of high-grade squamous intraepithelial lesions (HSIL) is a promising minimally invasive technique but its oncologic and functional outcomes are not well studied. The primary outcome was the efficacy of RFA, and the secondary outcomes were the functional and anatomical anal changes related to RFA. METHODS: This was a retrospective analysis of our prospectively collected database of patients who had RFA for HSIL at our institution, between August 2018 and March 2020. To be eligible for RFA, all patients had impairment of their immune function. Targeted ablation was applied in all cases, with 5 overlapping pulsations at the targeted HSILs (delivering 12 J/cm2 per application) followed by circumferential, 2-pulsation (12 J/cm2) overlapping anal ablation, to cover the entire anal transition zone. Patients were assessed for recurrence or metachronous disease at 3-month intervals by means of high-resolution anoscopy (HRA) and targeted biopsies. Anorectal manometry, endoanal ultrasound, the 36-Item Short Form and Massachusetts General Hospital-Sexual Functioning Questionnaire (MGH-SFQ) were assessed at baseline and 12 months after intervention. RESULTS: We included a total of 12 patients with anal HSILs. The mean age was 38.6 (± 7.68) years, and 7 (58.3%) were males. Six were HIV positive, 2 had a primary immunodeficiency disease, and 4 were receiving immunosuppressive therapy. A mean of 2.1 anal HSILs per patient were treated. At 12 months, high-resolution anoscopy showed that 7/12 (58.3%) patients had normal high-resolution anoscopy, 3/12 patients had recurrent HSILs, and 2/12 had a persistent lesion. Those lesions were treated with electrocautery, and reached complete response in the following the 6 months (total of 18 months). In particular, there were no metachronous lesions detected. Patients reported moderate to severe pain during the first 24 h after RFA, but only mild discomfort was present at 30 days. Patients were asymptomatic at their 6- and 12-month visits. RFA was not associated with changes in anorectal manometry or ultrasound examination. The 36-SF survey reported improvement in the general health domain (p = 0.038), while the MGH-SFQ showed improvements in sexual function. CONCLUSIONS: In this study, targeted plus circumferential RFA had a 58.3% efficacy rate for the treatment of anal HSIL in immunocompromised patients, achieving 100% eradication after adding electrocautery ablation. No metachronous lesions were detected. Patients presented relatively mild symptoms after the procedure, no changes in anorectal anatomy or function, and some improvements in their sexual function. These results seem promising in light of the high recurrence reported after HSIL treatment. Larger studies are needed to validate our results.

Immunosuppressant-induced cutaneous drug reactions in solid organ transplant recipients.

Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifestations, have a high prevalence but are rarely studied. We analyzed these manifestations' prevalence and their association with immunosuppressants in transplant recipients from a Brazilian tertiary center. Among 532 SOTRs followed at our dermatology clinic, 60 (11.3%) developed some cutaneous adverse reactions to the immunosuppressants, with a median age at transplantation of 50.5 years and a median life span posttransplantation of seven years. Acneiform eruption was the most common drug reaction found (21 patients, 30.4%), followed by diffuse non-scarring alopecia (16 patients, 23.1%), lymphedema (10 patients, 14.5%), gingival hyperplasia (7 patients, 10.1%), hypertrichosis (6 patients, 8.7%) and sebaceous hyperplasia (9 patients, 13.1%). Adequate immunosuppression is an essential prerequisite for successful organ transplantation. In the immediate post-transplant period, significant immunosuppression is needed, but after that, the complications of excessive immunosuppression outweigh the risk of organ rejection. SORTs may present with a broad spectrum of inflammatory and cosmetic findings due to immunosuppressants that can impair life quality.

COVID-19 in liver transplant recipients.

Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

Ethical and Legal Considerations on Organ Procurement from Executed Prisoners in China / Consideraciones éticas y legales sobre la obtención de órganos de presos ejecutados en China / Considerações Éticas e Legais sobre Obtenção de Órgãos de Prisioneiros Executados na China

Abstract In the past several decades, due to the severe shortage of transplantable organs, organ procurement from executed prisoners have been used to transplant organs, which goes against international ethics standards. As of January 2015, China phased out the use of executed prisoner organs and embarked on its transplant reform. Since then, many efforts have been made to meet the international ethics guidelines on organ transplants. In this study, we aim to elaborate on the status quo of organ procurement from executed prisoners from the perspective of ethics and law. Although China has made great progress in organ donation and transplantation, some Western transplant surgeons and bioethicists still hold outdated views on organ donation and transplantation in China, which will not bring any benefits to its development and will alienate it from the international transplant community. In this study, we propose that both the international transplant society and Chinese transplant community, with mutual cooperation and trust, should jointly make efforts to advance the development of organ donation and transplantation in China.

Resumen En las últimas décadas, debido a la grave escasez de órganos trasplantables, la obtención de órganos de presos ejecutados se ha utilizado para trasplantar órganos, lo que contraviene las normas éticas internacionales. A partir de enero de 2015, China eliminó gradualmente el uso de órganos de prisioneros ejecutados y se embarcó en su reforma de trasplantes. Desde entonces, se han realizado muchos esfuerzos para cumplir con las directrices éticas internacionales sobre trasplantes de órganos. En este estudio, nuestro objetivo es profundizar en el status quo de la obtención de órganos de presos ejecutados desde la perspectiva de la ética y la ley. Aunque China ha logrado un gran progreso en la donación y el trasplante de órganos, algunos cirujanos de trasplantes y bioéticos occidentales todavía tienen opiniones obsoletas sobre la donación y el trasplante de órganos en China, lo que no traerá ningún beneficio para su desarrollo y lo alejará de la comunidad internacional de trasplantes. En este estudio, proponemos que tanto la sociedad internacional de trasplantes como la comunidad china de trasplantes, con cooperación y confianza mutuas, deben hacer esfuerzos conjuntos para avanzar en el desarrollo de la donación y el trasplante de órganos en China.

Resumo Nas últimas décadas, devido à grave escassez de órgãos transplantáveis, a obtenção de órgãos de prisioneiros executados tem sido usada para o transplante de órgãos, o que vai contra padrões éticos internacionais. A partir de janeiro de 2015, a China eliminou o uso de órgãos de prisioneiros executados e lançou sua reforma em transplantes. Desde então, muitos esforços foram feitos para satisfazer diretrizes éticas internacionais sobre transplantes de órgãos. Nesse estudo, nós pretendemos estudar o status quo da obtenção de órgãos de prisioneiros executados desde uma perspectiva da ética e da lei. Embora a China tenha feito grandes progressos em doação e transplante de órgãos, alguns cirurgiões de transplantes e bioeticistas ocidentais ainda mantém visões desatualizadas sobre doação e transplante de órgãos na China, as quais não trarão quaisquer benefícios para seu desenvolvimento e irão aliená-las da comunidade de transplantes internacional. Nesse estudo, nós propomos que tanto a sociedade de transplante internacional e a comunidade de transplante chinesa, com cooperação e confiança mútuas, deveriam empreender esforços conjuntos para avançar o desenvolvimento de doação e transplante de órgãos na China.