Descemet Membrane Endothelial Keratoplasty in Children.

PURPOSE: To describe the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed in amblyopic aged (younger than 8 years) children. METHODS: This is a single-center retrospective study, including 11 eyes (7 congenital hereditary endothelial dystrophy and 4 congenital glaucoma) of 6 children in amblyopic age undergoing DMEK by a single surgeon (N.C.P.) at Sorocaba Eye Hospital from December 2015 to November 2017. Best spectacle-corrected visual acuity, biomicroscopy, pachymetry, endothelial cell density, and complications were evaluated. RESULTS: No intraoperative complications occurred. Graft detachment occurred in 1 eye (9.1%) and was successfully managed with rebubbling. No primary graft failure or pupillary block was observed. All pachymetric measurements improved, and the corneal edema clinically resolved in all eyes within 2 weeks after the procedure. At the last follow-up (mean 30 months), best spectacle-corrected visual acuity was ≥20/40 in 7 (77.8%) of 9 eyes from patients cooperative enough to assess vision. All children began visual stimulation therapy and amblyopic treatment within 1 month of surgery, and all grafts remained clear until the last follow-up. The mean preoperative donor endothelial cell density was 2588 ± 236 cells/mm, which decreased to 1726 ± 292 cells/mm 2 years after surgery, yielding a 33% reduction (P < 0.001). No immunologic graft reaction, secondary graft failure, or cataracts were observed during the follow-up period. CONCLUSIONS: In this series, DMEK was performed to successfully treat endothelial dysfunction in children. However, the procedure is more challenging, and more studies with more patients and longer follow-up are needed to confirm the superiority of DMEK in treating endothelial dysfunction in children.

Strategy to Enable and Accelerate Kidney Transplant in Small Children and Results of the First 130 Transplants in Children ≤15 kg in a Single Center.

BACKGROUND: Proper care of young children in need of kidney transplant (KT) requires many skilled professionals and an expensive hospital structure. Small children have lesser access to KT. METHODS: We describe a strategy performed in Brazil to enable and accelerate KT in children ≤15 kg based on the establishment of one specialized transplant center, focused on small children, and cooperating with distant centers throughout the country. Actions on 3 fronts were implemented: (a) providing excellent medical assistance, (b) coordinating educational activities to disseminate expertise and establish a professional network, and (c) fostering research to promote scientific knowledge. We presented the number and outcomes of small children KT as a result of this strategy. RESULTS: Three hundred forty-six pediatric KTs were performed in the specialized center from 2009 to 2017, being 130 in children ≤15 kg (38%, being 41 children ≤10 kg) and 216 in >15 kg (62%). Patient survival after 1 and 5 years of the transplant was 97% and 95% in the "small children" group, whereas, in the "heavier children" group, it was 99% and 96% (P = 0.923). Regarding graft survival, we observed in the "small children" group, 91% and 87%, whereas in the "heavier children" group, 94% and 87% (P = 0.873). These results are comparable to the literature data. Groups were similar in the incidence of reoperation, vascular thrombosis, posttransplant lymphoproliferative disease, and estimated glomerular filtration rate. CONCLUSIONS: The strategy allowed an improvement in the number of KT in small children with excellent results. We believe this experience may be useful in other locations.

Usefulness of Kidney Donor Profile Index (KDPI) to predict graft survival in a South Brazilian Cohort / Utilidade do Índice de Perfil de Doadores de Rins (KDPI) para prever a sobrevida do enxerto em uma coorte do Sul do Brasil

Abstract Introduction: Kidney Donor Profile Index (KDPI) has been incorporated in the United States to improve the kidney transplant allocation system. Objectives: To evaluate deceased kidney donors' profile using KDPI and compare to the previous United Network for Organ Sharing (UNOS) definition of expanded criteria donors (ECD) and assess the KDPI applicability to predict five-year graft survival and renal function in our sample. Methods: Retrospective cohort of 589 kidney transplants from deceased donors performed from January 2009 to May 2013 with follow-up until May 2018. Results: In 589 kidney transplants, 36.6% of donors were classified as ECD and 28.8% had KDPI ≥ 85%. Mean KDPI was 63.1 (95%CI: 60.8-65.3). There was an overlap of standard and ECD in KDPI between 60 and 95 and a significantly lower death-censored graft survival in KDPI ≥ 85% (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006. The AUC-ROC was 0.577 (95%CI: 0.514-0.641; p = 0.027). Renal function at 5 years was significantly lower according to the incremental KDPI (p < 0.002). KDPI (HR 1.011; 95%CI 1.001-1.020; p = 0.008), donor-specific antibodies (HR 2.77; 95%CI 1.69-4.54; p < 0.001), acute rejection episode (HR 1.73; 95%CI 1.04-2.86; p = 0.034) were independent and significant risk factors for death-censored graft loss at 5 years. Conclusion: In our study, 36.6% were classified as ECD and 28.8% had KDPI ≥ 85%. KDPI score showed a moderate power to predict graft survival at 5 years. Renal function was significantly lower in patients with higher KDPI.

Resumo Introdução: O Índice de Perfil de Doadores de Rins (KDPI) foi adotado nos Estados Unidos para melhorar o sistema de alocação de transplantes renais. Objetivos: avaliar o perfil dos doadores de rim falecidos usando o KDPI e comparar com a definição anterior do United Network for Organ Sharing (UNOS) de doadores de critérios expandidos (DCE) e avaliar a aplicabilidade do KDPI para prever a sobrevida do enxerto em cinco anos e a função renal em nossa amostra. Métodos: Coorte retrospectiva de 589 transplantes renais de doadores falecidos, realizada de janeiro de 2009 a maio de 2013, com acompanhamento até maio de 2018. Resultados: Em 589 transplantes renais, 36,6% dos doadores foram classificados como DCE e 28,8% apresentaram KDPI ≥ 85%. O KDPI médio foi de 63,1 (IC 95%: 60,8-65,3). Houve uma sobreposição de padrão e DCE no KDPI entre 60 e 95 e uma sobrevida do enxerto censurada por óbito significativamente menor no KDPI ≥ 85% (78,6%); KDPI 0-20: 89,8%, KDPI 21-59: 91,6% e KDPI 60-84: 83,0%; p = 0,006. A ASC-ROC foi de 0,577 (IC 95%: 0,514-0,641; p = 0,027). A função renal aos 5 anos foi significativamente menor de acordo com o aumento do KDPI (p <0,002). KDPI (HR 1.011; 95% CI 1.001-1.020; p = 0.008), anticorpos específicos contra doadores (HR 2,77; 95% CI 1,69-4,54; p <0,001), episódio de rejeição aguda (HR 1,73; 95% CI 1,04-2,86; p = 0,034) foram fatores de risco independentes e significativos para perda do enxerto censurada por óbito em 5 anos. Conclusão: Em nosso estudo, 36,6% foram classificados como DCE e 28,8% apresentaram KDPI ≥ 85%. O escore KDPI mostrou potencial moderado para prever a sobrevida do enxerto em 5 anos. A função renal foi significativamente menor nos pacientes com maior KDPI.

Usefulness of Kidney Donor Profile Index (KDPI) to predict graft survival in a South Brazilian Cohort.

INTRODUCTION: Kidney Donor Profile Index (KDPI) has been incorporated in the United States to improve the kidney transplant allocation system. OBJECTIVES: To evaluate deceased kidney donors' profile using KDPI and compare to the previous United Network for Organ Sharing (UNOS) definition of expanded criteria donors (ECD) and assess the KDPI applicability to predict five-year graft survival and renal function in our sample. METHODS: Retrospective cohort of 589 kidney transplants from deceased donors performed from January 2009 to May 2013 with follow-up until May 2018. RESULTS: In 589 kidney transplants, 36.6% of donors were classified as ECD and 28.8% had KDPI ≥ 85%. Mean KDPI was 63.1 (95%CI: 60.8-65.3). There was an overlap of standard and ECD in KDPI between 60 and 95 and a significantly lower death-censored graft survival in KDPI ≥ 85% (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006. The AUC-ROC was 0.577 (95%CI: 0.514-0.641; p = 0.027). Renal function at 5 years was significantly lower according to the incremental KDPI (p < 0.002). KDPI (HR 1.011; 95%CI 1.001-1.020; p = 0.008), donor-specific antibodies (HR 2.77; 95%CI 1.69-4.54; p < 0.001), acute rejection episode (HR 1.73; 95%CI 1.04-2.86; p = 0.034) were independent and significant risk factors for death-censored graft loss at 5 years. CONCLUSION: In our study, 36.6% were classified as ECD and 28.8% had KDPI ≥ 85%. KDPI score showed a moderate power to predict graft survival at 5 years. Renal function was significantly lower in patients with higher KDPI.

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.

Donor-host Lymphatic Anastomosis After Murine Lung Transplantation.

BACKGROUND: Establishing lung lymphatic drainage is thought to be important for successful lung transplantation. To date, there has been a complete absence of knowledge of how lymphatic connections are reestablished after lung transplant, despite evidence suggesting that this does indeed occur. The present study aimed to elucidate whether and how lymphatic anastomosis occurs after lung transplant. METHODS: An orthotopic murine model of lung transplant using lymphatic reporter mice and whole mount immunohistochemistry was used to evaluate the lymphatic vasculature and donor-host connections after lung transplantation. RESULTS: Immunohistochemistry of transplanted lungs demonstrated robust lymphatic vessels, and functional assays demonstrated lymphatic drainage in the transplanted lung that was comparable with that in native lungs. Lymphatic vessels in the donor lung exhibited active sprouting toward the host at the anastomosis within the first 3 days after lung transplantation, with more numerous and complex lymphatic sprouting developing thereafter. Donor lymphatic vessels were numerous at the site of anastomosis by day 14 after lung transplantation and formed physical connections with host lymphatic vessels, demonstrating a mechanism by which lymphatic drainage is reestablished in the transplanted lung. CONCLUSIONS: Lymphatic drainage after lung transplantation is established by active sprouting of donor lymphatic vessels towards the host and the formation of donor-host lymphatic connections at the level of the transplant anastomosis.

Kidney transplantation with donors in severe acute kidney injury. Should we use these organs? Retrospective Case Series / Transplante renal com doadores em lesão renal aguda severa. Devemos utilizar esses órgãos? Série de casos retrospectiva

ABSTRACT Introduction: The number of incident and prevalent patients on dialysis has increased, as well as the number of candidates for renal transplantation in Brazil, without a proportional increase in the number of organ donors. The use of expanded kidneys, as to renal function, may be an alternative to increase the supply of organs. Objective: to discuss the feasibility of using expanded kidneys for renal function, which are in severe acute renal injury. Methods: All cases of renal transplantation of deceased donors performed at the Hospital das Clínicas de Botucatu of UNESP, from January 2010 to June 2018, totaling 732 cases were evaluated. Cases with final donor creatinine greater than 6 mg/dL were selected. Results: four patients were selected, of whom all donors were in severe acute kidney injury (AKI). These donors presented rhabdomyolysis as a probable cause of severe AKI, were young, with no comorbidities and had decreased urinary volume in the last 24 hours. The clinical evolution of all the recipients was satisfactory, with a glomerular filtration rate after transplantation ranging from 48 to 98 mL/min/1.73 m2. Conclusion: this series of cases shows the possibility of using renal donors in severe AKI, provided the following are respected: donor age, rhabdomyolysis as the cause of AKI, and implantation-favorable biopsy findings. Additional studies with better designs, larger numbers of patients and longer follow-up times are needed.

RESUMO Introdução: O número de pacientes incidentes e prevalentes em diálise tem aumentado, assim como o número de candidatos ao transplante renal no Brasil, sem um aumento proporcional do número de doadores de órgãos. O uso de rins expandidos, quanto à função renal, pode ser uma alternativa para aumentar a oferta de órgãos. Objetivo: discutir a viabilidade do uso de rins expandidos quanto à função renal, que estejam em lesão renal aguda severa. Métodos: foram avaliados todos os casos de transplante renal de doador falecido realizados no Hospital das Clínicas de Botucatu da UNESP, de janeiro de 2010 a junho de 2018, totalizando 732 casos. Selecionou-se os casos com creatinina final do doador maior do que 6 mg/dL. Resultados: quatro pacientes foram selecionados, dos quais todos os doadores estavam em lesão renal aguda (LRA) severa. Esses doadores apresentavam rabdomiólise como provável causa de LRA severa, eram jovens, sem comorbidades e apresentavam diminuição de volume urinário nas últimas 24 horas. A evolução clínica de todos os receptores foi satisfatória, com taxa de filtração glomerular após o transplante variando entre 48 a 98 mL/min/1,73m2. Conclusão: essa série de casos mostra a possibilidade de utilização de doadores renais em LRA severa, desde que respeitadas as condições seguintes: idade do doador, rabdomiólise como causa de LRA e achados de biópsia favoráveis à implantação. Estudos adicionais com melhores desenhos, maior número de pacientes e maiores tempos de seguimento são necessários.

Kidney transplantation with donors in severe acute kidney injury. Should we use these organs? Retrospective Case Series.

INTRODUCTION: The number of incident and prevalent patients on dialysis has increased, as well as the number of candidates for renal transplantation in Brazil, without a proportional increase in the number of organ donors. The use of expanded kidneys, as to renal function, may be an alternative to increase the supply of organs. OBJECTIVE: to discuss the feasibility of using expanded kidneys for renal function, which are in severe acute renal injury. METHODS: All cases of renal transplantation of deceased donors performed at the Hospital das Clínicas de Botucatu of UNESP, from January 2010 to June 2018, totaling 732 cases were evaluated. Cases with final donor creatinine greater than 6 mg/dL were selected. RESULTS: four patients were selected, of whom all donors were in severe acute kidney injury (AKI). These donors presented rhabdomyolysis as a probable cause of severe AKI, were young, with no comorbidities and had decreased urinary volume in the last 24 hours. The clinical evolution of all the recipients was satisfactory, with a glomerular filtration rate after transplantation ranging from 48 to 98 mL/min/1.73 m2. CONCLUSION: this series of cases shows the possibility of using renal donors in severe AKI, provided the following are respected: donor age, rhabdomyolysis as the cause of AKI, and implantation-favorable biopsy findings. Additional studies with better designs, larger numbers of patients and longer follow-up times are needed.

Renal graft survival in patients transplanted from organs of deceased donors / Sobrevida del injerto renal en pacientes trasplantados de órganos de donadores fallecidos

Background: In Mexico, out of the total number of transplants it was reported, in 2014, a frequency of 29% of deceased donor renal transplantation (DDRT). The use of kidneys from deceased elderly donors is increasing over the years. Currently, some authors consider that six months after the transplant, patients who have been transplanted from deceased donors have a longer survival than those who are still undergoing dialysis replacement therapy. Objective: To observe and describe the results of renal graft function and survival of patients with DDRT during the first six months after transplantation, and show the frequencies of complications, as well as graft and death nephrectomy. Material and methods: A series of cases with taxonomy of retrospective, retrolective, descriptive with frequencies and correlational with association of variables, from January 2014 to July 2015; statistical analysis was performed using SPSS, version 17. Results: Renal graft's survival was 79.5%. Serum creatinine levels were 0.6 to 2.5 mg/dL with an average of 1.2. CKD-EPI index was estimated from 29 to 120 mL/min/1.73 m2 with an average of 71.4. We found 57% with glomerular filtration rate above 60 (the CKD-EPI level). Conclusion: DDRT continues to be a favorable option for patients with chronic renal failure, even with the extended criteria of the deceased donor.

Introducción: en nuestro país, del total de trasplantes se reportó, en el 2014, una frecuencia del 29% de trasplante renal de donador fallecido (TRDF). El uso de riñones procedentes de donante fallecido de edad avanzada está aumentando al paso de los años. Actualmente, algunos autores consideran que a los seis meses después del trasplante los pacientes que han sido trasplantados de donador fallecido tienen una mayor supervivencia que los que siguen aún en tratamiento sustitutivo con diálisis. Objetivo: observar y describir los resultados de la función y sobrevida del injerto renal de los pacientes con TRDF durante los primeros seis meses del postrasplante, y mostrar las frecuencias de complicaciones, así como también nefrectomía de injerto y defunción. Métodos: serie de casos con taxonomía de tipo retrospectivo, retrolectivo, descriptivo con frecuencias y correlacional con asociación de variables, realizada de enero del 2014 a julio del 2015; el análisis estadístico de las variables se hizo mediante el paquete SPSS, versión 17. Resultados: la sobrevida del injerto renal fue del 79.5%. Los niveles de creatinina sérica fueron de 0.6 a 2.5 mg/dL con una media de 1.2. El índice CKD-EPI se estimó de 29 a 120 mL/min/1.73 m2, con una media de 71.4. Encontramos un 57% con filtrado glomerular por arriba del 60 de CKD-EPI. Conclusión: el trasplante renal de donador fallecido continúa siendo una opción favorable para los pacientes con insuficiencia renal crónica, aun con los criterios extendidos del donador fallecido.

Optimizing survival of large fibula osteocutaneous flaps for extensive full-thickness oromandibular defects: A two-stage approach with temporary orocutaneous fistula.

INTRODUCTION: Composite and large head and neck defects requiring extensive skin-mucosa coverage are often reconstructed by combining flaps. Herein, we present a simple and reliable two-stage fibula osteocutaneous (FOC) flap technique to improve the survival of a large skin paddle for oromandibular reconstructions. METHODS: From October 2011 to September 2016, 47 patients with through-and-through oromandibular defects were reconstructed using FOC flaps with large skin paddles. To ensure optimum survival of skin paddles, temporary orocutaneous fistula were left in place and closed during the second stage operation via de-epithelialization of the skin paddle and suturing of mucosa. Demographic data, operative details, and postoperative complications were recorded. RESULTS: The skin paddle dimensions ranged from 20 to 31.5 cm in length and 12 to 17 cm in width with an average area of 430.4 cm2 (range 300-504). The average time between the two stages and hospital stay were 10 days and 14 days, respectively. Complications at the donor site included wound dehiscence (n = 3, 6.4%), partial skin graft loss (n = 3, 6.4%) and hematoma (n = 2, 4.3%). Recipient site complications included two (4.3%) early postoperative venous congestions that resolved after elevation and three (6.4%) partial skin flap necrosis (less than 5% surface area). All complications resolved with bedside conservative management. There was only one take-back for evacuation of recipient site hematoma (2.1%) but no flap loss. CONCLUSION: Two-staged large skin paddle FOC flaps can simplify reconstruction of extensive oromandibular defects by improving the reliability of the sizable skin paddle and negating the need for a second flap.

Soluble CD30, Acute Rejection, and Graft Survival: Pre- and 6-Month Post-Transplant Determinations-When Is the Best Time to Measure?

BACKGROUND: Pretransplantation soluble CD30 (sCD30) has been shown to be a good predictor of acute rejection (AR) and graft loss. This study aimed to evaluate the effectiveness of sCD30 measured pretransplant and up to 6 months after transplantation as a predictor of AR, graft loss, and survival at 5 years post-transplantation. Subjects were patients receiving living donor renal transplants at Bonsucesso Federal Hospital (Rio de Janeiro) in 2006 and between August 2010 and May 2011. METHODS: sCD30 was analyzed in samples collected pretransplantation and 7, 14, and 21, 28 days and 3, 4, 5, and 6 months post-transplantation from 73 kidney recipients. RESULTS: Patients in the AR group did not present a positive correlation with the sCD30 levels pretransplant (P = .54); in the post-transplant period, the 7- to 14-day samples showed patients with AR had higher levels of this biomarker (P = .036). The graft survival in 5 years of follow-up was not different between groups. CONCLUSIONS: The best time to predict AR using sCD30 is the 7- to 14-day sample; however, identifying and following the decrease of this biomarker from pre- to post-transplant seems to be better than just 1 measurement. The sCD30 post-transplant is another tool that may be used in monitoring patients after renal transplantation.

Minor Salivary Gland Transplantation for Severe Dry Eyes.

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.

Optimization and Standardization of the Immunodeficient Mouse Model for Assessing Fat Grafting Outcomes.

BACKGROUND: Animal models are often used to assess interventions that might improve fat grafting outcomes; however, there is great variability in the models. The authors sought to determine the predictive value of the immunocompromised mouse model for fat grafting so that experiments could be standardized and optimized. METHODS: Human lipoaspirate injections at different volumes and time points were assessed in a nude mouse model and compared with control injections of nonviable fat. Volume retention and explant histologic score were compared. In a separate study, interanimal reproducibility was determined by implanting a highly consistent hydrogel and measuring variability in volume retention. RESULTS: Injection volume significantly affects adipose resorption kinetics at 6 and 12 weeks. Masson trichrome staining revealed that macrophages were unable to infiltrate large (1 ml) grafts, and oil cysts were not absorbed by 18 weeks, which interfered with interpretation of volume retention data. Nonviable tissue was resorbed when grafts were 0.3 ml, and quantification of graft histologic viability correlated well with graft retention at all study time points. Interanimal variability was measured to be 8.44 percent of the mean retention volume for small graft volumes. CONCLUSIONS: Human fat graft retention in the immunodeficient mouse correlates with graft viability in small, 0.3-ml-volume grafts. However, centralized oil cysts in nonviable 1.0-ml grafts were not resorbed by 18 weeks and thus volume measurements were confounded and not significantly different from viable samples. In addition, tissue injury scores increased in initially healthy fat grafts at 18 weeks, possibly because of a delayed immune reaction.

Outcomes of Descemet Membrane Endothelial Keratoplasty in Patients With Previous Glaucoma Surgery.

PURPOSE: To evaluate outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes with previous trabeculectomy or a drainage device. METHODS: This is a retrospective study of 108 consecutive DMEK performed between October 2013 and December 2015. All eyes were divided into 3 groups: surgical treatment (ST) group, medical treatment (MT) group, and control group. Visual improvement, endothelial cell loss, and postoperative complications, including rejection, graft failure, and intraocular pressure elevation (≥25 mm Hg) were evaluated. RESULTS: The length of follow-up was 9.7 ± 7.3 months. Best-corrected visual acuity (BCVA) improved postoperatively in 85.3% of the ST group, 100% of the MT group, and 93% of the control (P = 0.24). Significantly more lines of BCVA were gained in the ST and MT groups (8.1 ± 8.1 and 9.2 ± 6.3 lines, respectively) than in the control (4.8 ± 5.6 lines, P < 0.05). The mean time to BCVA was 2.9 ± 2.8 months for the ST group, 4.7 ± 5.3 months for the MT group, and 3.0 ± 3.3 months for the control (P = 0.75). Endothelial cell loss was greater in the ST group (44.6 ± 17.8%) than in the MT group (29.9 ± 12.0%) and the control group (32.7 ± 11.3%, P = 0.001). There was one primary failure and no secondary graft failures. The overall rejection rate was 0.9%. Postoperative intraocular pressure elevation was less common in the ST group (14.7%) and control (23.3%) than in the MT group (50.0%, P = 0.04). There was no difference in the air injection rate among all groups (P = 1.0). CONCLUSIONS: DMEK in eyes with previous trabeculectomy and drainage device can result in very good short-term outcomes.

Experienced DSAEK Surgeon's Transition to DMEK: Outcomes Comparing the Last 100 DSAEK Surgeries With the First 100 DMEK Surgeries Exclusively Using Previously Published Techniques.

PURPOSE: To compare outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) when an experienced DSAEK surgeon transitions to DMEK while following 2 published endothelial keratoplasty surgical techniques. METHODS: This is a retrospective review of 200 eyes of 132 patients with Fuchs corneal dystrophy that underwent endothelial keratoplasty performed by one surgeon. Published, standardized techniques were followed for both DSAEK and DMEK. Postoperative complications were recorded. Best spectacle-corrected visual acuity (BSCVA), intraocular pressure, and central endothelial cell loss (ECL) were evaluated at 6 months postoperatively. RESULTS: There were no intraoperative complications. One DSAEK and 5 DMEK grafts developed graft detachment requiring rebubbling (P = 0.097). No iatrogenic primary graft failures occurred in the DSAEK group compared with one in the DMEK group. No pupil block episodes occurred in the DSAEK group compared with one in the DMEK group. Posterior synechiae formation occurred 15 times in the DMEK group and did not occur in the DSAEK group (P < 0.001). At 6 months, BSCVA was better in the DMEK group than in the DSAEK group (20/24; logMAR = 0.0844-20/32; logMAR = 0.2063) (P < 0.001). More eyes reached 20/20 or better BSCVA in the DMEK group compared with DSAEK (54.5%-13%) (P < 0.011). At 6 months, ECL was higher in the DMEK group than in the DSAEK group (31.9%-19.9%) (P < 0.001). CONCLUSIONS: Complications can be minimized and excellent outcomes can be achieved, without a steep learning curve, when an experienced DSAEK surgeon transitions to DMEK following a standardized technique. Six-month vision outcomes are better in the DMEK group; however, the rate of a newly described complication, posterior synechiae formation, and 6-month ECL are higher in the DMEK group than in the DSAEK group.

Is the combination of fat grafts and platelet rich plasma effective in rats?

PURPOSE:: To investigate if the association of fat grafts and platelet-rich plasma (PRP) improves graft viability in female rats. METHODS:: This is an experimental, randomized and blinded study, which involved 47 rats. Fat was harvested from the inguinal region and grafted to the cranial region. The experimental group consisted of PRP-enriched fat grafts (n=22) whilst the control group consisted of fat graft only (n=25). After a 100-day period, the animals were euthanised and the fat grafts were analyzed using scores from 0 (absent) to 4 (abundant), in optical microscopy by two independent and blinded pathologists. RESULTS:: Regarding fat graft cell viability, the PRP group scored moderate/abundant in 63% of cases and the fat graft only group scored absent/slight in 72% of cases (p=0.03). The PRP group also presented lower fat necrosis scores when compared to the fat graft only group (p=0.03). Tumors (dermoid cysts) within the fat grafts were observed in three animals in which the grafts were mixed with PRP. CONCLUSION:: Platelet-rich plasma improves the viability and integration of fat grafts in rats, but more studies are needed to fully understand the exact mechanisms that lead to this improvement and assess the safety of the method for use in humans.

Is the combination of fat grafts and platelet rich plasma effective in rats?

ABSTRACT PURPOSE: To investigate if the association of fat grafts and platelet-rich plasma (PRP) improves graft viability in female rats. METHODS: This is an experimental, randomized and blinded study, which involved 47 rats. Fat was harvested from the inguinal region and grafted to the cranial region. The experimental group consisted of PRP-enriched fat grafts (n=22) whilst the control group consisted of fat graft only (n=25). After a 100-day period, the animals were euthanised and the fat grafts were analyzed using scores from 0 (absent) to 4 (abundant), in optical microscopy by two independent and blinded pathologists. RESULTS: Regarding fat graft cell viability, the PRP group scored moderate/abundant in 63% of cases and the fat graft only group scored absent/slight in 72% of cases (p=0.03). The PRP group also presented lower fat necrosis scores when compared to the fat graft only group (p=0.03). Tumors (dermoid cysts) within the fat grafts were observed in three animals in which the grafts were mixed with PRP. CONCLUSION: Platelet-rich plasma improves the viability and integration of fat grafts in rats, but more studies are needed to fully understand the exact mechanisms that lead to this improvement and assess the safety of the method for use in humans.

Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation.

Pancreatic islet transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor islets and the need for long-term multidrug immunosuppression to prevent alloimmune islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic islets under the renal capsule to create an immunoregulatory microenvironment around the islet allograft. We achieved long-term engraftment of small loads of allogeneic islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following pancreatic ß-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3+ regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting islet allograft survival.

A Porcine Orthotopic Forelimb Vascularized Composite Allotransplantation Model: Technical Considerations and Translational Implications.

BACKGROUND: The restoration of complex tissue deficits with vascularized composite allotransplantation is a paradigm shift in reconstructive surgery. Clinical adoption of vascularized composite allotransplantation is limited by the need for systemic immunosuppression, with associated morbidity and mortality. Small-animal models lack the biological fidelity and preclinical relevance to enable translation of immunologic insights to humans. Large-animal models have been described; however, limitations persist, including the inability of heterotopic models to evaluate functional nerve regeneration, and the sensitivity of primates to toxicity of immunosuppressive drugs. The authors' novel orthotopic porcine limb transplant model has broad applicability and translational relevance to both immunologic and functional outcomes after vascularized composite allotransplantation. METHODS: Recipients underwent amputation at a level corresponding to the mid forearm. Replantation or transplantation of grafts was performed by plate fixation of the radio-ulna, microsurgical repair of brachial artery and median nerve, and extensor and flexor tendon repairs. Viability of replants was monitored clinically and radiologically. Transplants were monitored for clinicopathologic signs of rejection. Animals mobilized freely postoperatively. RESULTS: Replantations remained viable until the endpoint of 14 days. Transplants developed Banff grade 4 acute rejection by postoperative day 7. Doppler sonography and angiography confirmed vascular patency. Serial biopsy specimens of skin and histopathology of replants at endpoint confirmed tissue viability and bone healing. CONCLUSIONS: An orthotopic load-bearing porcine forelimb vascularized composite allotransplantation model was successfully established. Technical, procedural, and logistic considerations were optimized to allow model use for immunologic, bone healing, functional nerve regeneration, and other translational studies.