Patients' opinions 10 years after receiving encapsulated porcine islet xenotransplantation without immunosuppression.

BACKGROUND: Previously we performed clinical encapsulated neonatal porcine islet transplantation under comprehensive regulation, and demonstrated the efficacy and safety. To analyze the patients' quality of life (QOL), we assessed patients' opinions 10 years after islet xenotransplantation. METHODS: Twenty-one type 1 diabetic patients received microencapsulated neonatal porcine islet transplants in Argentina were enrolled. Seven patients were enrolled in efficacy and safety study and 14 patients were enrolled in safety studies. Patients' opinions related to the current and pre-transplant status of diabetes control, blood glucose levels, severe hypoglycemia, and hyperglycemia required hospitalization were analyzed. In addition, opinions related to islet xenotransplantation were assessed. RESULTS: At the time of this survey, average HbA1c was still significantly lower compared to pre-transplantation (8.5 ± 0.9 (%) at pre-transplant and 7.4 ± 0.5(%) at the survey, p < .05) and average insulin dose were also lower (0.95 ± 0.32 (IU/kg) at pre-transplant and 0.73 ± 0.27 (IU) at the survey). The majority of patients improved diabetes control (71%), blood glucose levels (76%), severe hypoglycemia (86%) and hyperglycemia required hospitalization (76%), and no patients deteriorated in all of the categories when compared with pre-transplantation. No patients had cancer, or psychological problem, and one patient had a serious adverse event. The majority of patients wanted to recommend this treatment to other patients (76%) and receive booster transplantation (85.7%). CONCLUSIONS: The majority of patients had positive opinions related to the encapsulated porcine islet xenotransplantation 10 years after transplantation.

Long-term follow-up for the microbiological safety of clinical microencapsulated neonatal porcine islet transplantation.

Enrollment in three clinical trials for microencapsulated neonatal porcine islet xenotransplantation to treat unstable type 1 diabetic patients concluded in November 2014. In this study, we report a long-term follow-up assessment of microbiological safety for these trials. Thirty-eight type 1 diabetic patients received microencapsulated neonatal porcine islet transplants. Islets were isolated and prepared from the pancreata of New Zealand (NZ) based designated pathogen-free (DPF) pigs under GMP conditions. Blood samples of thirty-six patients were collected from 5 to 7 years post-first transplant and were tested by real-time PCR for porcine circovirus-1 (PCV1), porcine circovirus-2 (PCV2), porcine lymphotropic herpesvirus 1 (PLHV1), porcine lymphotropic herpesvirus 2 (PLHV2), and porcine cytomegalovirus (PCMV). To detect porcine endogenous retrovirus (PERV), specific real-time PCR and product enhanced reserve transcriptase (PERT) assays were performed. PCV1, PCV2, PLHV1, PLHV2, PCMV, PERV, and reverse transcriptase (RT) activity remained undetected in all tested samples indicating no viral transmission. Except for one patient that died due to complications unrelated to the transplant, there were no significant adverse events. Microbiological safety was demonstrated for microencapsulated neonatal porcine islet xenotransplantation from 5-7 years post-transplantation consistent with earlier reports.

Level of acceptance of islet cell and kidney xenotransplants by personnel of hospitals with and without experience in clinical xenotransplantation.

BACKGROUND: Recently, significant progress in both safety and efficacy has been achieved in the field of xenotransplantation, as exemplified by results from the first clinical trials of porcine islet transplantation. It would be of interest to learn whether the attitude of the clinical staff involved in such trials changes as the trials are carried out in their own hospital. METHODS: One hundred and four clinical staff members from the Eva Peron Hospital of San Martin (Buenos Aires, Argentina) where clinical trials of islet xenotransplantation have been performed and 92 similar staff members from the Diego Thompson Hospital (Buenos Aires, Argentina) where no such xenotransplantation has been carried out participated in the study. Data were collected anonymously using questionnaires. RESULTS: Statistically significant differences between the acceptance of xenotransplantation by clinical personnel in a hospital that had carried out clinical xenotransplantation trials were observed when compared with the acceptance of a similar staff from the hospital that had not carried out such trials. CONCLUSION: This study shows that involvement in clinical xenotransplantation trials significantly changes the attitude of the clinical staff towards this technology and suggests that better information given to the society may increase acceptance of the xenotransplantation.

Pig islet xenotransplantation acceptance in a Latin-American diabetic population.

Progress in porcine islet xenotransplantation has been accompanied by studies on acceptance of this new procedure by patients, health professionals or the general public. Such studies have not been done in the Latin-American population. We conducted a questionnaire in 108 diabetes patients (insulin-dependent, n = 53; insulin-independent, n = 55) in a public hospital in Argentina. The questions addressed the general perception of the xenotransplant procedure and specific items related to the outcome (achieving insulin independence, improvement in metabolic control, delay in emergence of diabetic complications, need for repeat procedures, potential of transfer of infectious viruses, association with psychological problems, and anticipated success in relation to achieving a cure). Eighty-six (79%) of the patients accepted islet xenotransplantation; this incidence was not different for insulin-dependent or insulin-independent patients, patients with or without complications, or patients with good or poor metabolic control. Also, over 75% of patients accepted the procedure if this is only associated with a reduction in insulin requirement, if the procedure just delays but not prevents the onset of complications, or if the procedure needs to be performed every 6 months. Fifty-seven percent of patients indicated acceptance even if the potential transmission of a virus infection cannot be completely ruled out: this outcome was not affected by the outbreak of the H1N1 flu epidemic during the conduct of this study. Forty percent of patients indicated that living with porcine cells in their body could give psychological problems. We conclude that this population of Latin-American diabetic patients shows a high acceptance rate of a porcine islet xenotransplantation product.

No PERV transmission during a clinical trial of pig islet cell transplantation.

Xenotransplantation of pig islet cells is a promising alternative for the treatment of diabetes with insulin and may help to prevent numerous late complications such as blindness and amputation. First encouraging results using porcine islets have been reported in preclinical animal models as well in the first clinical trial in New Zealand. The goal of this manuscript is to examine the biological safety of a second trial performed in Argentina, specifically in regards to the transmission of porcine endogenous retroviruses (PERVs) using improved detection methods As in the first trial encapsulated islet cells from the well-characterised Auckland Island pigs were used. The animals were not genetically modified. The islet cells were transplanted in eight human recipients using a modified clinical protocol. Sera taken at different time points after transplantation (up to 55 weeks) were screened for the presence of antibodies against PERV proteins by Western blot analysis using viral antigens from highly purified virus particles. Positive sera obtained by immunization with recombinant PERV proteins were used as control sera. In none of the patients antibodies against PERV were detected, indicating the absence of infection. In parallel at different time points (up to 113 weeks) white blood cells (WBC) have been tested for PERV DNA, and WBC and plasma for PERV RNA by real-time RT-PCR. All tests were negative. In addition, using primers detecting pig mitochondrial cytochrome oxidase (COX) gene, patients were screened for microchimerism. In summary, the data are further evidence for the safety of pig islet cell transplantation.

Clinical Benefit of Islet Xenotransplantation for the Treatment of Type 1 Diabetes.

BACKGROUND: Allogeneic islet transplantation has become a viable option for the treatment of unstable type 1 diabetes. However, the donor shortage and the necessity of the immunosuppressive drugs are two major issues. To solve these issues, we performed islet xenotransplantation using encapsulated neonatal porcine islets without immunosuppressive drugs. METHODS: Two different doses (approximately 5000IEQ/kg and 10,000IEQ/kg) of encapsulated neonatal porcine islets were transplanted twice (total approximately 10,000IEQ/kg and 20,000IEQ/kg) into four type 1 diabetic patients in each group (total 8 patients). FINDINGS: In the higher dose group, all four patients improved HbA1c. This was maintained at a level of <7% for >600days with significant reduction of the frequency of unaware hypoglycemic events. INTERPRETATION: The clinical benefit of islet xenotransplantation with microencapsulation has been shown.

Progress in Clinical Encapsulated Islet Xenotransplantation.

At the 2015 combined congress of the Cell Transplant Society, International Pancreas and Islet Transplant Association, and International Xenotransplantation Association, a symposium was held to discuss recent progress in pig islet xenotransplantation. The presentations focused on 5 major topics - (1) the results of 2 recent clinical trials of encapsulated pig islet transplantation, (2) the inflammatory response to encapsulated pig islets, (3) methods to improve the secretion of insulin by pig islets, (4) genetic modifications to the islet-source pigs aimed to protect the islets from the primate immune and/or inflammatory responses, and (5) regulatory aspects of clinical pig islet xenotransplantation. Trials of microencapsulated porcine islet transplantation to treat unstable type 1 diabetic patients have been associated with encouraging preliminary results. Further advances to improve efficacy may include (1) transplantation into a site other than the peritoneal cavity, which might result in better access to blood, oxygen, and nutrients; (2) the development of a more biocompatible capsule and/or the minimization of a foreign body reaction; (3) pig genetic modification to induce a greater secretion of insulin by the islets, and/or to reduce the immune response to islets released from damaged capsules; and (4) reduction of the inflammatory response to the capsules/islets by improvements in the structure of the capsules and/or in genetic engineering of the pigs and/or in some form of drug therapy. Ethical and regulatory frameworks for islet xenotransplantation are already available in several countries, and there is now a wider international perception of the importance of developing an internationally harmonized ethical and regulatory framework.

Trasplante de islotes pancreáticos: estado actual / Transplantation of Pancreatic Islets of Lagerhans: present status

El trasplante clínico de islotes luego del protocolo de Edmonton, presenta en centros de excelencia una reversión de l enfermedad del 80 por ciento de los pacientes al año del implante. Sin embargo la necesidad de utilizar dos o más páncreas pra curar a un solo paciente y la inmunosupresión crónica limitan el proceso a pacientes diabéticos lábiles exclusivamente. En esta revisión se analizan las distintas estrategias para superar estos inconvenientes y extender el procedimiento a todos los pacientes diabéticos tipo I

Estudio de la mortalidad en traumatizados en un servicio de emergencia / Mortality study in trauma on emergency service

Se analizan 73.548 pacientes atendidos por el Servicio de Emergencia en un período de 10 años. Las injurias se clasificaron por su topografía, especificando cantidad de internaciones, número de operaciones. La mortalidad en las 2 primeras horas en traumatismos severos fue del 2,44%y la alejada del 5,38%. Se realizaron consideraciones en cuanto a si distribución y frecuencia

Reversión de la diabetes en el ratón por el xenotrasplante de islotes porcinos en un páncreas bioartificial / Reversion of diabetes type I in the mice with diffusion chambers of pig islets an bioartificial pancreas model

Antecedentes: El páncreas bioartificial permitiría la utilización de islotes porcinos para la reversión de la diabetes tipo I en humanos. Distintos modelos se han creado hasta el presente, presentando diversos problemas, que limitan su aplicación clínica. Objetivo: Evaluar el modelo de páncreas bioartificial, con cámaras de difusión en un xenotrasplante discordante (cerdo-ratón). Material y Métodos: Ratones hembras diabéticos por Streptozotocin, fueron utilizados como receptores de islotes porcinos. Se introdujeron en agarosa, 2000 islotes en cada cámara, formadas con arandelas de acrílico adheridas a 2 membranas semipermeables de policarbonato. El diseño experimental: Grupo 1 (n = 4): 4000 islotes porcinos no encapsulados en cápsula renal. Grupo 2 (n = 4): 1 cámara c/u en el abdomen. Grupo 3 (n = 6): 2 cámaras c/u. Grupo 4 (n = 2): 3 cámaras c/u. Se evaluó en cada grupo las variaciones de glucemia y la reacción histológica pericámara. Resultados: En el grupo 1, la reversión de la diabetes no superó los 3 días. De los 12 ratones con cámaras de difusión, el 50 por ciento alcanzó la normoglucemia, manteniéndose en el 33,3 por ciento hasta la 5ta. semana fecha en la que se sacrificaron. Ninguno de los ratones con una cámara normaliza la glucemia, como en el 100 por ciento de los que poseían tres. Importante reacción inflamatoria pericámara, se halla en la 1era. y 5ta. semana. Conclusiones: Resultados auspiciosos; necesidad de ampliar la experiencia utilizando 6000 o más islotes por ratón, y un mayor número de estos para encontrar nuevas estrategias que disminuyan la inflamación pericámara, mejorando a largo plazo la supervivencia del injerto

Cirurgía de urgencia por síndrome de fosa ilíaca derecha: nuestra experiencia / Emergency surgey for right iliac fossa syndrome: our experience

Se analizan las causas de 3.043 intervenciones quirúrgicas de urgencia por síndrome de fosa ilíaca derecha. La patología apendicular resultó ser la más frecuente (94,37%) seguida por causas ginecológicas (5,04%), divertículo del ciego complicado (0,26%), inflamación del divertículo de Mekel (0,19%), carcinoma cecal perforado (0,09%), invaginación intestinal (0,06%) y colecistitis aguda (0,03%). Las conductas adoptadas fueron: a) apendicectomía en la patología apendicular; b) salpingectomía y ooforectomía parcial o total de acuerdo al caso, en los ginceológicos; c) hemicolectomía derecha o cecostomía en las diverticulitis cecales; d) diverticulectomía o resección intestinal en las complicaciones de Meckel; e) hemicolectomía derecha en la perforación del carcinoma cecal; f) reducción o reseción intestinal en la invaginación intestinal y g) colecistectomía en la colescistitis aguda. Se destaca que los cirujanos intercinientes swben estar entrenados para reconocer y resolver las distintas patologías que se pueden presentar, recordando la importancia del análisis anatomopatológico de todas las piezas resecadas