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1.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38635784

RESUMO

CASE: We describe the unique case of a 20-year-old man with a history of Legg-Calve-Perthes disease, hip dysplasia, and osteochondral fragmentation of the medial femoral head. We performed arthroscopic femoroplasty and femoral head allografting, followed by a valgus-producing derotational femoral osteotomy (DFO) and periacetabular osteotomy (PAO). At 1-year follow-up, the patient achieved osseous union and complete femoral head healing with return to his active hobbies. CONCLUSION: We describe the successful utilization of arthroscopic allografting for medial femoral head osteochondral fragmentation. To our knowledge, this is the first report on femoral head arthroscopic allografting before DFO and PAO.


Assuntos
Cabeça do Fêmur , Doença de Legg-Calve-Perthes , Masculino , Humanos , Adulto Jovem , Adulto , Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/cirurgia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/cirurgia , Doença de Legg-Calve-Perthes/complicações , Osteotomia , Fêmur/cirurgia , Progressão da Doença , Aloenxertos
2.
J Vet Sci ; 25(2): e22, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38568824

RESUMO

BACKGROUND: Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons. OBJECTIVE: The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits. METHODS: Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at -80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment. RESULTS: The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group. CONCLUSIONS: Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon.


Assuntos
Tendão do Calcâneo , Plasma Rico em Plaquetas , Traumatismos dos Tendões , Coelhos , Animais , Tendão do Calcâneo/cirurgia , Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Traumatismos dos Tendões/terapia , Traumatismos dos Tendões/veterinária , Traumatismos dos Tendões/patologia , Cicatrização , Aloenxertos/patologia
3.
Ren Fail ; 46(1): 2333919, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38575330

RESUMO

Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.


Assuntos
Hiperparatireoidismo Secundário , Hiperparatireoidismo , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Paratireoidectomia/efeitos adversos , Estudos Retrospectivos , Hiperparatireoidismo/etiologia , Hiperparatireoidismo/cirurgia , Aloenxertos , Hiperparatireoidismo Secundário/cirurgia , Hiperparatireoidismo Secundário/complicações , Hormônio Paratireóideo
4.
JBJS Case Connect ; 14(2)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38579102

RESUMO

CASE: A 27-year-old woman developed capitellar osteonecrosis after long-term corticosteroid use to treat non-Hodgkin lymphoma. She underwent an osteochondral reconstruction using a lateral femoral condyle (LFC) allograft. This graft was selected because it has a similar radius of curvature to the capitellum. The patient had osseous integration, painless, near full range of motion of her elbow 6 months postoperatively and good shoulder function 1.0 year postoperatively. CONCLUSION: The LFC allograft should be considered a viable option in treating capitellar osteonecrosis.


Assuntos
Osteocondrite Dissecante , Osteonecrose , Feminino , Humanos , Adulto , Cotovelo , Osteocondrite Dissecante/cirurgia , Transplante Ósseo , Epífises/cirurgia , Osteonecrose/cirurgia , Aloenxertos
5.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612654

RESUMO

Kidney transplantation is an essential medical procedure that significantly enhances the survival rates and quality of life for patients with end-stage kidney disease. However, despite advancements in immunosuppressive therapies, allograft rejection remains a leading cause of organ loss. Notably, predictions of cellular rejection processes primarily rely on biopsy analysis, which is not routinely performed due to its invasive nature. The present work evaluates if the serum proteomic fingerprint, as acquired by Fourier Transform Infrared (FTIR) spectroscopy, can predict cellular rejection processes. We analyzed 28 serum samples, corresponding to 17 without cellular rejection processes and 11 associated with cellular rejection processes, as based on biopsy analyses. The leave-one-out-cross validation procedure of a Naïve Bayes model enabled the prediction of cellular rejection processes with high sensitivity and specificity (AUC > 0.984). The serum proteomic profile was obtained in a high-throughput mode and based on a simple, rapid, and economical procedure, making it suitable for routine analyses and large-scale studies. Consequently, the current method presents a high potential to predict cellular rejection processes translatable to clinical scenarios, and that should continue to be explored.


Assuntos
Transplante de Rim , Humanos , Teorema de Bayes , Proteômica , Qualidade de Vida , Aloenxertos
6.
J Cardiothorac Surg ; 19(1): 204, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615010

RESUMO

INTRODUCTION: There are enough cases of colorectal cancer with liver metastasis, but inferior vena cava infiltraion with dissemination to the right atrium is an infrequent event. PRESENTATION OF CASE: This is the first case of surgical treatment of recurrent liver metastasis with the infiltration to the inferior vena cava and to the right atrium of the heart, using a cryopreserved pulmonary homograft. DISCUSSION: The choice of a cryopreserved pulmonary homograft was preferred by the need for a radical and wide resection of tissues involved in the metastasis, as well as to potentially reduce the risk of thrombosis in the short- and long-term postoperative period. CONCLUSION: The use of a cryopreserved homograft in operation undergoing cardiopulmonary bypass allowed us to perform the required volume of radical resection and to replace an extended section of the inferior vena cava.


Assuntos
Ponte Cardiopulmonar , Neoplasias Hepáticas , Humanos , Seguimentos , Átrios do Coração/cirurgia , Aloenxertos
8.
Ren Fail ; 46(1): 2336126, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38627208

RESUMO

AIM: Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). METHODS: This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: 'COVID', 'Renal', 'Kidney', 'Transplant', and 'Rejection'. The results from controlled and uncontrolled studies were separately collated and analyzed. RESULTS: A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. CONCLUSION: In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.


Assuntos
COVID-19 , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Imunossupressores/efeitos adversos , COVID-19/complicações , Rim , Aloenxertos , Rejeição de Enxerto , Transplantados
9.
Clin Transplant ; 38(4): e15314, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38628057

RESUMO

Kidney transplantation is a highly effective treatment for end-stage kidney disease. However, allograft rejection remains a significant clinical challenge in kidney transplant patients. Although kidney allograft biopsy is the gold-standard diagnostic method, it is an invasive procedure. Since the current monitoring methods, including screening of serum creatinine and urinary protein, are not of sufficient sensitivity, there is a need for effective post-transplant monitoring to detect allograft rejection at an early stage. Extracellular vesicles are vesicles with a lipid bilayer that originate from different cell types in pathological and physiological conditions. The content of extracellular vesicles reflects the status of cells at the time of their production. This review comprehensively summarizes clinical, in vivo, and in vitro reports that highlight the potential of extracellular vesicles as diagnostic biomarkers for kidney allograft rejection. Clarification would facilitate differentiation between rejection and non-rejection and identification of the mechanisms involved in the allograft rejection. Despite increasing evidence, further research is necessary to establish the clinical utility of extracellular vesicles in the diagnosis and monitoring of allograft rejection in kidney transplant recipients. Using extracellular vesicles as non-invasive biomarkers for diagnosis of kidney allograft rejection could have tremendous benefits in improving patient outcomes and reduce the need for invasive procedures.


Assuntos
Vesículas Extracelulares , Rim , Humanos , Rim/patologia , Transplante Homólogo , Biomarcadores/urina , Aloenxertos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia
10.
Rom J Ophthalmol ; 68(1): 60-64, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617728

RESUMO

Aim: To present a complex case of Ahmed tube exposure 6 months after the implantation associated with corneal melting and iris prolapse, and the surgical reposition that required multiple allografts and limbal reconstruction. Methods: A 60-year-old patient arrived at the emergency room with tube exposure combined with corneal melting and iris prolapse from a previously placed Ahmed valve 6 months prior. Our approach was to use one corneoscleral graft to repair the melted cornea and avoid further iris prolapse and a second scleral graft to cover the repositioned tube. Upon completion of conjunctival dissection, cleaning and deepithelization of the melted cornea and the tube by application of alcohol 100% followed. A new entry point was made for the tube and was covered using an alcohol-preserved scleral allograft and the previous entry point was repaired using a corneoscleral allograft with the corneal aspect restoring the limbus and avoiding further iris protrusion. Results: 6 months follow-up of the patient showed excellent recovery, anatomical restoration, and IOP normalization. Conclusion: Surgical repair of these cases can be very demanding, and requires surgical improvisation and prolonged surgical time. The literature remains very limited on how a surgeon should approach similar cases, which are the crucial tips, and which are the missteps that should be avoided. In this case, we used multiple scleral/corneoscleral allografts in a specific orientation and different sutures to reconstruct the damaged limbal area and restore the anatomy. Abbreviations: VA = Visual Acuity, GDD = Glaucoma Drainage Device, IOP = Intra Ocular Pressure.


Assuntos
Úlcera da Córnea , Glaucoma , Humanos , Pessoa de Meia-Idade , Glaucoma/complicações , Glaucoma/diagnóstico , Córnea , Iris , Etanol , Aloenxertos
11.
Sci Rep ; 14(1): 9137, 2024 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644422

RESUMO

To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm2 or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.


Assuntos
Glioma , Lasers Semicondutores , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Animais , Fotoquimioterapia/métodos , Glioma/tratamento farmacológico , Glioma/patologia , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Camundongos , Lasers Semicondutores/uso terapêutico , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Modelos Animais de Doenças , Aloenxertos , Apoptose/efeitos dos fármacos , Masculino
12.
Acta Ortop Mex ; 38(1): 60-65, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38657154

RESUMO

Patellofemoral instability (PFI) is a common disorder in children and adolescents. Surgical stabilization of the patella poses challenges in skeletally immature patients due to anatomical peculiarities at this stage, leading to the absence of an established standard reconstruction technique. Recently, there has been a notable interest in the medial patellofemoral complex (MPFC), encompassing the medial patellofemoral ligament (MPFL) and the medial quadriceps tendon femoral ligament (MQTFL), owing to their role in restricting lateral patellar displacement. This paper aims to describe the surgical technique employed by the author for reconstructing the medial patellofemoral complex with allograft in skeletally immature patients with patellofemoral instability. Study design: surgical technique.


La inestabilidad patelofemoral (PFI) es un trastorno común en niños y adolescentes. La estabilización quirúrgica de la rótula plantea desafíos en pacientes esqueléticamente inmaduros debido a peculiaridades anatómicas en esta etapa, lo que lleva a la ausencia de una técnica de reconstrucción estándar establecida. Recientemente, ha habido un interés notable en el complejo femororrotuliano medial (MPFC), que abarca el ligamento femororrotuliano medial (MPFL) y el ligamento femoral del tendón del cuádriceps medial (MQTFL), debido a su papel en la restricción del desplazamiento rotuliano lateral. Este artículo tiene como objetivo describir la técnica quirúrgica empleada por el autor para reconstruir el complejo femororrotuliano medial con aloinjerto en pacientes esqueléticamente inmaduros con inestabilidad femororrotuliana. Diseño del estudio: técnica quirúrgica.


Assuntos
Aloenxertos , Instabilidade Articular , Articulação Patelofemoral , Humanos , Articulação Patelofemoral/cirurgia , Criança , Adolescente , Instabilidade Articular/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Ortopédicos/métodos
13.
Front Immunol ; 15: 1389105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660296

RESUMO

Background: Progressive decline of allograft function leads to premature graft loss. Forkhead box P3 (FOXP3), a characteristic gene of T-regulatory cells, is known to be essential for auto-antigen tolerance. We assessed the hypothesis that low FOXP3 mRNA splice variant levels in peripheral blood cells early after transplantation are associated with progressive allograft injury. Methods: Blood samples were prospectively collected from 333 incident kidney transplant recipients on the first and 29th postoperative day. We used quantitative polymerase chain reaction to determine transcripts of 3 isotypes of FOXP3 splice variants, including pre-mature FOXP3 and full length FOXP3 (FOXP3fl). We investigated the association between FOXP3 splice variant levels and the declines in estimated glomerular filtration rate (eGFR) of more than 5ml/min/1.73m2 within the first-year post-transplant using logistic regression. Results: We observed lower FOXP3fl levels in recipients with declining eGFR (N = 132) than in recipients with stable eGFR (N = 201), (logarithmic value -4.13 [IQR -4.50 to -3.84] vs -4.00 [4.32 to -3.74], p=0.02). In ad hoc analysis pre-transplant FOXP3fl levels were similar in both groups. The association between FOXP3fl and declining eGFR was confirmed by multivariable analysis adjusted for potential confounding factors (Odds Ratio 0.51, 95% confidence interval 0.28 to 0.91: p=0.02). When stratifying FOXP3fl levels into quartiles, recipients with lower day1 FOXP3fl had the highest rate of declining eGFR (p=0.04). Conclusion: Low FOXP3fl splice variant levels at the first postoperative day in kidney transplant recipients were associated with severe decline of eGFR, a well-known surrogate for hard endpoints.


Assuntos
Fatores de Transcrição Forkhead , Transplante de Rim , Isoformas de Proteínas , Tolerância ao Transplante , Transplante de Rim/efeitos adversos , Humanos , Fatores de Transcrição Forkhead/genética , Masculino , Feminino , Pessoa de Meia-Idade , Tolerância ao Transplante/genética , Adulto , Isoformas de Proteínas/genética , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/genética , Aloenxertos/imunologia , Processamento Alternativo , Idoso
14.
Cell Mol Biol (Noisy-le-grand) ; 70(3): 67-77, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38650153

RESUMO

Osteoinduction, and/or osteoconduction, and antibacterial characteristics are prerequisites for achieving successful bone grafting. This study aimed to coat bone allografts with silver nanoparticles and assess their antibacterial activity and biocompatibility compared to uncoated bone allografts. In this study, the bone allografts were coated with varying concentrations of silver nanoparticles (5 mg/l, 10 mg/l, and 50 mg/l) through a simple adsorption technique. Subsequently, the coated samples underwent characterization using SEM, FTIR, EDS, and XRD. The Minimal Inhibitory Concentration (MIC) of the silver nanoparticles was determined against Staphylococcus aureus and Streptococcus mutans. Bacterial growth inhibition was evaluated by measuring turbidity and performing a disk diffusion test. Moreover, qualitative investigation of biofilm formation on the coated bone allograft was conducted using SEM. Following this, MG-63 cell lines, resembling osteoblasts, were cultured on the bone allografts coated with 5 mg/l of silver nanoparticles, as well as on uncoated bone allografts, to assess biocompatibility. The MIC results demonstrated that silver nanoparticles exhibited antimicrobial effects on both microorganisms, inhibiting the growth of isolates at concentrations of 0.78 mg/L for Staphylococcus aureus and 0.39 mg/L for Streptococcus mutans. The bone allografts coated with varying concentrations of silver nanoparticles exhibited significant antibacterial activity against the tested bacteria, completely eradicating bacterial growth and preventing biofilm formation. The osteoblast-like MG-63 cells thrived on the bone allografts coated with 5 mg/l of silver nanoparticles, displaying no significant differences compared to both the uncoated bone allografts and the control group.  Within the limit of this study, it can be concluded that silver nanoparticles have a positive role in controlling graft infection. In addition, simple adsorption technique showed an effective method of coating without overwhelming the healing of the graft.


Assuntos
Aloenxertos , Antibacterianos , Biofilmes , Substitutos Ósseos , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Prata , Staphylococcus aureus , Streptococcus mutans , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Streptococcus mutans/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Humanos , Biofilmes/efeitos dos fármacos , Substitutos Ósseos/química , Substitutos Ósseos/farmacologia , Aloenxertos/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química , Transplante Ósseo/métodos , Teste de Materiais , Linhagem Celular
15.
Transpl Int ; 37: 12556, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38650846

RESUMO

Macrophages contribute to post-transplant lung rejection. Disulfiram (DSF), an anti-alcoholic drug, has an anti-inflammatory effect and regulates macrophage chemotactic activity. Here, we investigated DSF efficacy in suppressing acute rejection post-lung transplantation. Male Lewis rats (280-300 g) received orthotopic left lung transplants from Fisher 344 rats (minor histocompatibility antigen-mismatched transplantation). DSF (0.75 mg/h) monotherapy or co-solvent only (50% hydroxypropyl-ß-cyclodextrin) as control was subcutaneously administered for 7 days (n = 10/group). No post-transplant immunosuppressant was administered. Grades of acute rejection, infiltration of immune cells positive for CD68, CD3, or CD79a, and gene expression of monocyte chemoattractant protein and pro-inflammatory cytokines in the grafts were assessed 7 days post-transplantation. The DSF-treated group had significantly milder lymphocytic bronchiolitis than the control group. The infiltration levels of CD68+ or CD3+ cells to the peribronchial area were significantly lower in the DSF than in the control groups. The normalized expression of chemokine ligand 2 and interleukin-6 mRNA in allografts was lower in the DSF than in the control groups. Validation assay revealed interleukin-6 expression to be significantly lower in the DSF than in the control groups. DSF can alleviate acute rejection post-lung transplantation by reducing macrophage accumulation around peripheral bronchi and suppressing pro-inflammatory cytokine expression.


Assuntos
Dissulfiram , Rejeição de Enxerto , Transplante de Pulmão , Macrófagos , Ratos Endogâmicos F344 , Ratos Endogâmicos Lew , Animais , Transplante de Pulmão/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Masculino , Dissulfiram/farmacologia , Dissulfiram/uso terapêutico , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Aloenxertos , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Quimiocina CCL2/metabolismo , Pulmão/patologia , Pulmão/efeitos dos fármacos
16.
Microsurgery ; 44(4): e31172, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38651631

RESUMO

BACKGROUND: Post-oncologic surgical reconstruction of lower limbs in pediatrics remains a challenging topic. Microsurgical techniques allow reconstructions of large bony defects. The use of vascularized fibular flap with allograft has proven to be an ideal biologic construct. We aim to assess the success rate of this operation, including flap survival, bony union, weight-bearing ambulation, and complications in a long-term follow-up in our case series compared to the literature. PATIENTS AND METHODS: Our case-series includes 18 femoral resections (9 osteosarcomas, 8 Ewing sarcoma, and 1 desmoid tumor) and 15 tibial resections (10 osteosarcoma, 4 Ewing sarcoma, and 1 Malignant Fibrous Histiocytoma). We collected patients' demographics, type of tumor, type of resection, defect size, fibula-flap length, method of fixation, anastomosis site, follow-up data, complications, and their management. All survivals were examined by X-ray and CT-scan to evaluate the morphological changes of the vascularized fibula and follow-up. The functional evaluation was performed by the 30-point Musculoskeletal Tumor Society Rating Score (MSTS) for the lower limb (Enneking et al., Clinical Orthopaedics and Related Research 1993(286):241-246). RESULTS: The mean age of the femur resection patients' group was 11.2 years with a mean defect size of 14 cm and a mean length of the fibular flap of 18 cm; for the tibia the mean age was 12 years with a mean defect size of 14 cm and a mean length of the fibular flap of 16.6 cm. The overall survival of the reconstructions at 5 years follow-up was 17 out 18 cases for the femur and 13 out of 15 cases for the tibia. MSTS score was 28.2 for the femur and 23.7 for the tibia. The average time of union of the fibula was seen after 5 months, while allograft consolidation was observed around 19.7 months. The mean time of follow-up was 144.5 months for the femur and 139.2 months for the tibia. The complication rate observed was 7 out of 18 for the femur and 7 out of 15 for the tibia reconstructions. CONCLUSIONS: The viability of the fibula is a cornerstone in the success of reconstruction as well as the successful management of complications in intercalary defects after tumor resection in pediatrics to restore good functionality. Our results are in line with those reported in the literature in terms of overall complication rates. The high primary union of allograft, the high MSTS score obtained, and the low rate of severe complications reflect the mechanical role of this reconstructive technique over a long follow-up.


Assuntos
Neoplasias Ósseas , Fíbula , Microcirurgia , Procedimentos de Cirurgia Plástica , Tíbia , Humanos , Criança , Fíbula/transplante , Fíbula/irrigação sanguínea , Masculino , Feminino , Neoplasias Ósseas/cirurgia , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Tíbia/cirurgia , Estudos Retrospectivos , Fêmur/cirurgia , Fêmur/transplante , Seguimentos , Resultado do Tratamento , Transplante Ósseo/métodos , Pré-Escolar , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/transplante , Aloenxertos , Sarcoma de Ewing/cirurgia , Retalhos Cirúrgicos/irrigação sanguínea , Retalhos Cirúrgicos/transplante , Sobrevivência de Enxerto
17.
Commun Biol ; 7(1): 454, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609465

RESUMO

Chronic antibody mediated rejection (AMR) is the major cause of solid organ graft rejection. Th17 contributes to AMR through the secretion of IL17A, IL21 and IL22. These cytokines promote neutrophilic infiltration, B cell proliferation and donor specific antibodies (DSAs) production. In the current study we investigated the role of Th17 in transplant sensitization. Additionally, we investigated the therapeutic potential of novel inverse agonists of the retinoic acid receptor-related orphan receptor gamma t (RORγt) in the treatment of skin allograft rejection in sensitized mice. Our results show that RORγt inverse agonists reduce cytokine production in human Th17 cells in vitro. In mice, we demonstrate that the RORγt inverse agonist TF-S14 reduces Th17 signature cytokines in vitro and in vivo and leads to blocking neutrophilic infiltration to skin allografts, inhibition of the B-cell differentiation, and the reduction of de novo IgG3 DSAs production. Finally, we show that TF-S14 prolongs the survival of a total mismatch grafts in sensitized mice. In conclusion, RORγt inverse agonists offer a therapeutic intervention through a novel mechanism to treat rejection in highly sensitized patients.


Assuntos
Citocinas , Agonismo Inverso de Drogas , Humanos , Animais , Camundongos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Células Th17 , Aloenxertos , Imunoglobulina G
18.
Sci Rep ; 14(1): 5345, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438513

RESUMO

Managing patients with kidney allografts largely depends on biopsy diagnosis which is based on semiquantitative assessments of rejection features and extent of acute and chronic changes within the renal parenchyma. Current methods lack reproducibility while digital image data-driven computational models enable comprehensive and quantitative assays. In this study we aimed to develop a computational method for automated assessment of histopathology transformations within the tubulointerstitial compartment of the renal cortex. Whole slide images of modified Picrosirius red-stained biopsy slides were used for the training (n = 852) and both internal (n = 172) and external (n = 94) tests datasets. The pipeline utilizes deep learning segmentations of renal tubules, interstitium, and peritubular capillaries from which morphometry features were extracted. Seven indicators were selected for exploring the intrinsic spatial interactions within the tubulointerstitial compartment. A principal component analysis revealed two independent factors which can be interpreted as representing chronic and acute tubulointerstitial injury. A K-means clustering classified biopsies according to potential phenotypes of combined acute and chronic transformations of various degrees. We conclude that multivariate analyses of tubulointerstitial morphometry transformations enable extraction of and quantification of acute and chronic components of injury. The method is developed for renal allograft biopsies; however, the principle can be applied more broadly for kidney pathology assessment.


Assuntos
Transplante de Rim , Humanos , Reprodutibilidade dos Testes , Rim , Biópsia , Aloenxertos
19.
PLoS One ; 19(3): e0301281, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547092

RESUMO

Early allograft dysfunction (EAD) is a functional hepatic insufficiency within a week of orthotopic liver transplantation (OLT) and is associated with morbidity and mortality. The etiology of EAD is multifactorial and largely driven by ischemia reperfusion injury (IRI), a phenomenon characterized by oxygen scarcity followed by paradoxical oxidative stress and inflammation. With the expanded use of marginal allografts more susceptible to IRI, the incidence of EAD may be increasing. This necessitates an in-depth understanding of the innate molecular mechanisms underlying EAD and interventions to mitigate its impact. Our central hypothesis is peri-reperfusion hyperoxemia and immune dysregulation exacerbate IRI and increase the risk of EAD. We will perform a pilot prospective single-center observational cohort study of 40 patients. The aims are to determine (1) the association between peri-reperfusion hyperoxemia and EAD and (2) whether peri-reperfusion perturbed cytokine, protein, and hypoxia inducible factor-1 alpha (HIF-1α) levels correlate with EAD after OLT. Inclusion criteria include age ≥ 18 years, liver failure, and donation after brain or circulatory death. Exclusion criteria include living donor donation, repeat OLT within a week of transplantation, multiple organ transplantation, and pregnancy. Partial pressure of arterial oxygen (PaO2) as the study measure allows for the examination of oxygen exposure within the confines of existing variability in anesthesiologist-administered fraction of inspired oxygen (FiO2) and the inclusion of patients with intrapulmonary shunting. The Olthoff et al. definition of EAD is the primary outcome. Secondary outcomes include postoperative acute kidney injury, pulmonary and biliary complications, surgical wound dehiscence and infection, and mortality. The goal of this study protocol is to identify EAD contributors that could be targeted to attenuate its impact and improve OLT outcomes. If validated, peri-reperfusion hyperoxemia and immune perturbations could be targeted via FiO2 titration to a goal PaO2 and/or administration of an immunomodulatory agent by the anesthesiologist intraoperatively.


Assuntos
Falência Hepática , Transplante de Fígado , Humanos , Adolescente , Transplante de Fígado/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Sobrevivência de Enxerto , Fígado/metabolismo , Estudos de Coortes , Aloenxertos , Reperfusão , Oxigênio/metabolismo , Estudos Observacionais como Assunto
20.
Am J Sports Med ; 52(5): 1238-1249, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38523473

RESUMO

BACKGROUND: Osteochondral allograft transplantation (OCAT) is an accepted knee joint-preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. PURPOSE: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. RESULTS: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. CONCLUSION: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.


Assuntos
Meniscos Tibiais , Qualidade de Vida , Humanos , Masculino , Feminino , Adulto , Estudos de Coortes , Seguimentos , Meniscos Tibiais/transplante , Análise por Pareamento , Articulação do Joelho/cirurgia , Reoperação , Aloenxertos
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