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1.
Clin Plast Surg ; 49(1): 137-148, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34782132

RESUMO

To manage the deficient nasal dorsum, a thorough knowledge of dorsal augmentation techniques should be mastered by the rhinoplasty specialist. Indications for dorsal augmentation may arise in both primary and revision rhinoplasty presentations. To direct operative planning, a complete facial analysis, noting the importance of maintaining overall nasofacial balance, is essential. An array of techniques, including autologous and nonautologous (ie, allogeneic and synthetic) sources, have been used globally-each carrying its own advantages and disadvantages. The authors believe autologous grafts to be the optimal source for dorsal augmentation because of their biocompatibility and ability to produce natural and long-lasting outcomes.


Assuntos
Fáscia , Rinoplastia , Fáscia/transplante , Humanos , Nariz/cirurgia , Coleta de Tecidos e Órgãos , Transplante Autólogo
2.
Exp Neurol ; 347: 113913, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34752785

RESUMO

INTRODUCTION: Neural stem cell (NSC) transplantation offers great potential for treating ischemic stroke. Clinically, ischemia followed by reperfusion results in robust cerebrovascular injury that upregulates proinflammatory factors, disrupts neurovascular units, and causes brain cell death. NSCs possess multiple actions that can be exploited for reducing the severity of neurovascular injury. Our previous studies in young adult mice showed that human NSC transplantation during the subacute stage diminishes stroke pathophysiology and improves behavioral outcome. METHODS: We employed a well-established and commonly used stroke model, middle cerebral artery occlusion with subsequent reperfusion (MCAO/R). Here, we assessed the outcomes of hNSC transplantation 48 h post-MCAO (24 h post-transplant) in aged mouse brains in response to stroke because aging is a crucial risk factor for cerebral ischemia. Next, we tested whether administration of the integrin α5ß1 inhibitor, ATN-161, prior to hNSC transplantation further affects stoke outcome as compared with NSCs alone. RNA sequencing (RNA-seq) was used to assess the impact of hNSC transplantation on differentially expressed genes (DEGs) on a transcriptome-wide level. RESULTS: Here, we report that hNSC-engrafted brains with or without ATN-161 showed significantly reduced infarct size, and attenuated the induction of proinflammatory factors and matrix metalloproteases. RNA-seq analysis revealed DEGs and molecular pathways by which hNSCs induce a beneficial post-stroke outcome in aged stroke brains. 811 genes were differentially expressed (651 downregulated and 160 upregulated) in hNSC-engrafted stroke brains. Functional pathway analysis identified enriched and depleted pathways in hNSC-engrafted aged mouse stroke brains. Depletion of pathways following hNSC-engraftment included signaling involving neuroinflammation, acute phase response, leukocyte extravasation, and phagosome formation. On the other hand, enrichment of pathways in hNSC-engrafted brains was associated with PPAR signaling, LXR/RXR activation, and inhibition of matrix metalloproteases. Hierarchical cluster analysis of DEGs in hNSC-engrafted brains indicate decreased expression of genes encoding TNF receptors, proinflammatory factors, apoptosis factors, adhesion and leukocyte extravasation, and Toll-like receptors. CONCLUSIONS: Our study is the first to show global transcripts differentially expressed following hNSC transplantation in the subacute phase of stroke in aged mice. The outcome of our transcriptome study would be useful to develop new therapies ameliorating early-stage stroke injury.


Assuntos
Envelhecimento/genética , Células-Tronco Neurais/fisiologia , Transplante de Células-Tronco/métodos , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/terapia , Transcriptoma/fisiologia , Envelhecimento/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Células Cultivadas , Infarto Cerebral/genética , Infarto Cerebral/metabolismo , Infarto Cerebral/terapia , Feto , Regulação da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/transplante , Oligopeptídeos/administração & dosagem , Acidente Vascular Cerebral/metabolismo , Transcriptoma/efeitos dos fármacos
3.
FASEB J ; 36(1): e22056, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34939223

RESUMO

Brown adipose tissue (BAT) transplantation is a promising means of increasing whole-body energy metabolism to ameliorate obesity. However, the changes in BAT following transplantation and the effects of the microenvironment of the recipient site on graft function have yet to be fully characterized. Therefore, we aimed to determine the effects of transplanting BAT from C57BL/6 mice into the dorsal subcutaneous region or deep to the quadriceps femoris muscle of leptin-deficient ob/ob mice. Subcutaneously transplanted BAT lost features of BAT and demonstrated greater inflammatory cell infiltration and more oil cysts 16 weeks following transplantation. By contrast, the sub-muscularly transplanted BAT maintained features of BAT and was more highly vascularized. Interestingly, sub-muscular BAT transplantation led to a significant increase in oxygen consumption and less inflammation in subcutaneous fat, which was associated with long-term reductions in insulin resistance and body mass gain, whereas the subcutaneous transplants failed after 16 weeks. These results demonstrate that the beneficial effects of BAT transplantation depend upon the microenvironment of the recipient site. Skeletal muscle may provide a microenvironment that maintains the inherent features of BAT grafts over a long period of time, which facilitates a reduction in obesity and improvements in glucose homeostasis.


Assuntos
Tecido Adiposo Marrom , Microambiente Celular , Resistência à Insulina , Músculo Esquelético/metabolismo , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/transplante , Animais , Masculino , Camundongos , Camundongos Obesos , Obesidade/patologia , Obesidade/terapia
4.
Bull Cancer ; 108(10S): S162-S167, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34920799

RESUMO

CAR-T cells belong to a new class of biological medicines, referred to as Advanced Therapy Medicinal Products (ATMPs). Despite the cellular component, according to the regulatory definition, CAR-T cells are gene therapy medicines, a sub-category of ATMPs, since their therapeutic effect is the result of their genetic modification. The specificity and the complexity of these innovative drugs have required a complete reorganization of the hospital and pharmaceutical circuits, from the cell collection to the drug administration to the patient. Indeed, increased interaction and collaboration between different healthcare professionals is essential in order to guarantee the quality and safety of these innovative medicines.


Assuntos
Engenharia Celular/legislação & jurisprudência , Terapia Genética/legislação & jurisprudência , Imunoterapia Adotiva/legislação & jurisprudência , Receptores de Antígenos Quiméricos , Linfócitos T , Composição de Medicamentos/normas , Indústria Farmacêutica/legislação & jurisprudência , Indústria Farmacêutica/normas , Europa (Continente) , França , Terapia Genética/métodos , Humanos , Imunoterapia Adotiva/métodos , Linfócitos T/imunologia , Linfócitos T/transplante
5.
Bull Cancer ; 108(10S): S4-S17, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34920806

RESUMO

Chimeric antigen receptors (CAR)-T cells are genetically engineered T-lymphocytes redirected with a predefined specificity to any target antigen, in a non-HLA restricted manner, therefore combining antibody-type specificity with effector T-cell function. This strategy was developed some thirty years ago, after extensive work established the key role of the immune system against cancer. The first-engineered T-cell with chimeric molecule was designed in 1993 by Israeli immunologist Zelig Eshhar. Since then, several modifications took place, including the addition of co-stimulatory domain, to further improve CAR-T cell anti-tumor potency. The first clinical application of CAR-T cell was done in Rotterdam in 2005 for metastatic renal cell carcinoma and simultaneously at the National Cancer Institute (NCI) for metastatic ovarian cancer. These pioneered studies failed to demonstrate a therapeutic benefit, but warning emerged concerning their safety of use. The real clinical success came with anti-CD19 CAR-T cells, used since 2009 by Steven Rosenberg at the NCI in a patient with refractory follicular lymphoma and in 2011 by Carl June and David Porter from the University of Pennsylvania in patients with chronic lymphocytic leukemia and B-cell acute lymphoblastic leukemia. From that time, large centers in North America have embarked in several early phase and pivotal trials that have demonstrated unprecedent response rate in heavily pretreated chemo refractory patient with B-cell malignancies. Theses clinical success have led to the approval of three anti-CD19 CAR-T cells products for the management of B-cell malignancies in the United States and in Europe as of December 2020.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias/terapia , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante , Especificidade de Anticorpos , Antígenos CD19/imunologia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Ensaios Clínicos como Assunto , Europa (Continente) , Feminino , História do Século XVIII , História do Século XIX , História do Século XX , Humanos , Imunoterapia Adotiva/história , Israel , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Leucemia Linfocítica Crônica de Células B/terapia , Depleção Linfocítica/métodos , Linfócitos do Interstício Tumoral/transplante , Linfoma Folicular/terapia , Mieloma Múltiplo/terapia , Neoplasias/imunologia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Linfócitos T/imunologia , Estados Unidos
6.
Bull Cancer ; 108(10S): S73-S80, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34920810

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy represents a major breakthrough in the field of hematology. "Off-the-shelf" allogeneic CAR T-cells from donors have many potential advantages over autologous approaches, such as the immediate availability of cryopreserved batches, possible standardization of the cell product, time for multiple cell modifications, redosing and decreased cost. However, allogeneic T-cells possess foreign immunological identities that can lead to graft-versus-host disease (GvHD) and their rejection by the host immune system. In this review, we describe the different approaches to produce allogeneic CAR T-cells with limited potential for GvHD and that can persist in the recipient. The preliminary clinical results obtained with the first generation of allogeneic CAR T-cells are presented as well as the perspectives in hematological malignancies and solid tumors.


Assuntos
Células Alógenas/citologia , Doença Enxerto-Hospedeiro/prevenção & controle , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/transplante , Células Alógenas/imunologia , Bancos de Espécimes Biológicos , Edição de Genes/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Doença Enxerto-Hospedeiro/imunologia , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Antígenos de Histocompatibilidade Classe I/imunologia , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/transplante , Depleção Linfocítica , /transplante , Neoplasias/imunologia , Neoplasias/terapia , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia
7.
Cells ; 10(12)2021 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-34943842

RESUMO

Spinal cord injury (SCI) is a devastating condition of the central nervous system that strongly reduces the patient's quality of life and has large financial costs for the healthcare system. Cell therapy has shown considerable therapeutic potential for SCI treatment in different animal models. Although many different cell types have been investigated with the goal of promoting repair and recovery from injury, stem cells appear to be the most promising. Here, we review the experimental approaches that have been carried out with pluripotent stem cells, a cell type that, due to its inherent plasticity, self-renewal, and differentiation potential, represents an attractive source for the development of new cell therapies for SCI. We will focus on several key observations that illustrate the potential of cell therapy for SCI, and we will attempt to draw some conclusions from the studies performed to date.


Assuntos
Células-Tronco Pluripotentes/transplante , Traumatismos da Medula Espinal/terapia , Regeneração da Medula Espinal , Animais , Ensaios Clínicos como Assunto , Células-Tronco Embrionárias/transplante , Humanos , Células-Tronco Pluripotentes Induzidas/transplante
8.
Artigo em Inglês | MEDLINE | ID: mdl-34787966

RESUMO

Replacements for diseased aortic valves are limited. Repair of the aortic valve is performed by only a few surgeons. A novel technique of aortic valve reconstruction using autologous pericardium shows promising results. In this video tutorial, we demonstrate the Ozaki procedure using an ex vivo low fidelity simulation.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Valva Aórtica/cirurgia , Humanos , Pericárdio/transplante , Reimplante
9.
Kyobu Geka ; 74(12): 1012-1016, 2021 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-34795144

RESUMO

The patient was a 61-year-old man with neurofibromatosis typeⅠ, who had several papules in a whole body. Medical history included atrial fibrillation and cerebral embolism. Transthoracic and transesophageal echocardiogram revealed severe mitral valve regurgitation and tricuspid valve regurgitation due to annular dilation with atrial enlargement, tethering of the posterior mitral leaflet, the anterior mitral leaflet prolapse with chordal rupture. Mitral valve repair and tricuspid annuloplasty, maze procedure were performed via median sternotomy. Mitral valve repair was performed by chorda reconstruction with artificial chordae to A2, patch-augmentation of the posterior leaflet with 0.6% glutaraldehyde-treated autologous pericardial patch and ring annuloplasty. There was no abnormal bleeding during surgery, and surgical site infection was not observed. Postoperative echocardiogram showed the augmented posterior leaflet created a deep and tightly uniform coaptation to the anterior leaflet and mitral regurgitation was well controlled.


Assuntos
Insuficiência da Valva Mitral , Prolapso da Valva Mitral , Neurofibromatoses , Humanos , Masculino , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/cirurgia , Pericárdio/transplante
10.
Acta Biomed ; 92(5): e2021435, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34738555

RESUMO

To the Editor, The first uterus transplantation (UTx) to be successfully carried out in Italy occurred at the Transplant Center of the Policlinico di Catania, on 21st August 2020. The patient, a 30-year-old woman with absolute uterine factor infertility (AUFI) due to Rokitansky syndrome, is now set to undergo a medically assisted reproductive procedure aimed at implanting her own oocytes, which had been stored via cryopreservation, following in vitro fertilization. Only UTx from deceased donors has been approved in Italy, although most UTx attempts and live births worldwide have been achieved from live donors, mostly closely related to the recipient (1). If UTx becomes a mainstream surgical practice for women who could not otherwise experience pregnancy, such an option will mark a point where the set of moral and ethical precepts which we espouse could soon become obsolete. Still, UTx is undoubtedly a milestone bound to give rise to even more complex bioethical issues. In fact, it encompasses the ethical complexities inherent in MAP as well as those arising from its status as a non-life saving transplantation, but rather a "life-giving" one (2). Moreover, since the development of UTx was primarily motivated by the potential to allay dissatisfaction and unhappiness stemming from the discrepancy between procreative ability and reproductive aspirations, it can be viewed as "life-enhancing" as well. An important framework providing perspective is the revised version of the Montreal Criteria for the Ethical Feasibility of Uterine Transplantation (3). Nevertheless, such a set of criteria is emblematic of how fast scientific innovation can outpace fundamental bioethics standards, and may itself be already outdated, in that it requires the recipient to be a "genetic female", whereas research on the possibility to perform UTx on transgender women is already in progress. That future scenario goes to the heart of UTx and its fundamental purpose: not life-saving but, as far as transgender women are concerned, life-enhancing. Research has clarified the primary motivation for which transgender women would opt for UTx. Findings from a recent survey unequivocally reflect the "life-enhancing" purpose: an overwhelming 90% majority of respondents expressed the belief that having a transplanted, functioning uterus and vagina would benefit their sex life and perceived sense of femininity, improving quality of life overall (4). Such findings are rather similar to those regarding the perceptions of biological women with AUFI: 95% of respondents in a UK study exploring the attitudes of women toward uterus transplant stated that, despite the additional risks posed, they would choose uterus transplant over surrogacy and adoption (5). Hence, it is not unreasonable to assume that in transgender women, UTx may go a long way towards the achievement of reproductive aspirations, benefit quality of life overall, and be effective in allaying dysphoric symptoms. After all, gender dysphoria entails discomfort and even distress with one's biological sex. It has the potential to severely affect quality of life overall. Treating gender dysphoria in transgender women relies on a multidisciplinary approach involving medical, psychological, and surgical specialists. Psychological input, hormonal therapy, or gender affirmation surgery are all potential options according to a highly individualized assessment for each patient. Nonetheless, UTx intended as a means for transgender women to foster their sense of femininity does present considerable contraindications. UTx is in fact ephemeral in nature: following childbirth, the graft has to be removed in order to eliminate the need for immunosuppressive medications. If on the other hand UTx were performed for reasons other than reproduction, i.e. to improve dysphoric symptoms, the duration of the graft would have to be significantly longer, hence a worse risk-benefit ratio. From a merely reproductive perspective, however, it is worth bearing in mind that transgender women may deem pregnancy as the final and conclusive stage in the process of reconfiguring their life aspirations according to the gender with which they psychologically identify. Certainly, the safety of the procedure into a biologically male body will likely be more complicated and risky than performing UTx in a female body. One of the pioneer scientists who first mastered UTx has acknowledged that transgendered pregnancy may be feasible, but in addition to the anatomical barriers, he has expressed ethical concerns (6). The fundamental ethical question that needs an answer is: if UTx becomes mainstream, safe and effective for biological women with AUFI, would there be any morally tenable grounds as to why transgender women should be denied such an opportunity for gestation? In countries where transgendered women who have transitioned are granted the same legal rights as their female counterparts, this will become a relevant question if UTx is offered as clinical treatment in women. Arguably, UTx and ever more innovative MAP procedures pose ethical quandaries bound to grow as such practices become available on a large scale (7). Already, in vitro fertilization entails the separation between sexuality and procreation, which has made it possible for same-sex couples and singles to have children through heterologous fertilization (8). Such practices are governed with varying degrees of restrictions by each country, which reflects the diversity of approaches in terms of ethical acceptability (9). Advances in embryo manipulation through genome editing could soon pave the way for the eradication of diseases before birth, or even the enhancement of humans yet to be born (10), a whole new frontier in beginning of life bioethics for which we are unprepared. Ultimately, we feel it may all go down to whether procreative liberty ought to be deemed as entailing an absolute right to gestate, and whether transgender women can be denied such a right without infringing upon ethical precepts of equality and non-discrimination. Current bioethics approaches need to undergo a radical update if we are to successfully meet the challenges posed by fast-growing scientific advances, set to shape and mold our lives ever more dramatically.


Assuntos
Bioética , Infertilidade Feminina , Adulto , Feminino , Humanos , Infertilidade Feminina/cirurgia , Masculino , Motivação , Gravidez , Qualidade de Vida , Útero/transplante
11.
Curr Opin Organ Transplant ; 26(6): 664-668, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34636768

RESUMO

PURPOSE OF REVIEW: Uterus transplantation (Utx) offers women with absolute uterine factor infertility the opportunity to carry their own pregnancies. As Utx transitions from an experimental to standard clinical procedure, we review the status of the ethical issues applicable to the stakeholders involved. RECENT FINDINGS: With more than 65 Utx procedures reported to date, evidence is accruing that enables the chance of success - a live birth - for the recipient to be weighed against the risks the recipient incurs through the Utx process, as well as risks to living donors undergoing surgery, to children exposed in utero to immunosuppressants and the uterine graft environment, and to third parties related to uterus procurement from multiorgan deceased donors. Experience has also informed aspects of recipient and donor autonomy that must be safeguarded. SUMMARY: Clinical trial results provides a basis for weighing the interests of the stakeholders implicated in Utx, and so can inform transplant centers' and regulatory bodies' development of policies and protocols that will determine access to Utx and allocation of organs, together with other considerations of justice. Additional evidence, particularly on long-term outcomes, is needed, and new questions can be expected to arise as access to and indications for Utx broaden.


Assuntos
Infertilidade Feminina , Transplante de Órgãos , Criança , Feminino , Humanos , Infertilidade Feminina/cirurgia , Doadores Vivos , Transplante de Órgãos/efeitos adversos , Gravidez , Útero/transplante
12.
Curr Opin Organ Transplant ; 26(6): 616-626, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34636769

RESUMO

PURPOSE OF REVIEW: Women with absolute uterine factor infertility, because of uterine absence, or the presence of a nonfunctional uterus, were regarded as being untreatable until 2014 when the first birth following uterus transplantation (UTx) took place in Sweden. This proof-of-concept occurred in a woman with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHs) with congenital uterine absence, who received a uterus from a 61-year-old live donor (LD). Since then, several births after UTx have occurred in Sweden and subsequently in other countries, including both LD and deceased donor (DD) transplants. A great majority of the recipients were women with MRKHs. The efficiency and safety of UTx can be determined only when a complete study cohort of transplanted women have reached the definitive endpoint of graft hysterectomy. The different outcomes of transplanted women include graft failure, as well as graft survival with failure to achieve livebirth, or livebirth(s). Published data from a completed trial are not yet available. The results that we have to rely on are reports of completed surgeries and interim outcomes that may be as early as a few months after surgery and up to several years after UTx. The purpose of this review is to give an update on all published clinical UTx data and major results, including live births up to mid 2021. RECENT FINDINGS: The interim results of a number of UTx studies have been published. LD UTx procedures have been reported from four European countries (Sweden, the Czech Republic, Germany, Spain), four Asian nations (Saudi Arabia, India, China, Lebanon), as well as some from the USA. DD UTx procedures have been reported from Turkey, the Czech Republic, the USA and Brazil. To our knowledge, there also exist unpublished UTx cases from some of the countries mentioned above and from at least four other countries (Serbia, France, Mexico, Italy). We estimate that at least 80 UTx procedures have been performed, resulting in more than 40 births. The present study includes only data from published, peer-reviewed, research papers. The results of 62 UTx cases show an overall surgical success rate, as defined by a technically successful transplantation with a subsequent regular menstrual pattern, of 76%. The success rates for LD and DD UTx procedures were 78% and 64%, respectively. The rate of serious postsurgical complications requiring invasive or radiological intervention was 18% for LDs and 19% for recipients. The cumulative live birth rate in successful UTx procedures is estimated to be above 80%. Twenty-four births after UTx have been reported and the results show a high rate of preterm birth, with an associated high proportion of respiratory distress syndrome. SUMMARY: UTx has proven to be a successful treatment for uterine factor infertility at several centers around the world. The modest success rate and the fairly high complication rate among LDs, indicate that further research and development under strict governance are needed before this option should be widely offered.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual , Infertilidade Feminina , Nascimento Prematuro , Anormalidades Urogenitais , Transtornos 46, XX do Desenvolvimento Sexual/diagnóstico , Transtornos 46, XX do Desenvolvimento Sexual/cirurgia , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/cirurgia , Masculino , Pessoa de Meia-Idade , Ductos Paramesonéfricos , Gravidez , Útero/transplante
13.
Curr Opin Organ Transplant ; 26(6): 660-663, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34620782

RESUMO

PURPOSE OF REVIEW: Policy development for uterus transplantation (UTx) is in its infancy. Understanding current oversight of UTx programmes can inform further development. RECENT FINDINGS: Currently, the United States has the most comprehensive regulations for UTx. Much of the policy outside the USA is focused on candidate selection. In the USA, UTx is categorized as, and follows policies of, a vascular composite allograft. Some considerations for UTx have not yet been addressed in policy, including the need for candidates to have a viable embryo before listing and transplantation, additional factors that may be warranted in organ allocation and the need to report data on the infant as well as the recipient. SUMMARY: Oversight of UTx falls within the governance of solid organ transplantation with unique aspects to be considered. Guidelines for multidisciplinary care, transplant-focused infrastructure and defined outcome metrics found in other solid organ transplant programmes provide a useful framework for UTx programmes.


Assuntos
Infertilidade Feminina , Transplante de Órgãos , Feminino , Humanos , Políticas , Transplante Homólogo , Estados Unidos , Útero/transplante
14.
Nat Commun ; 12(1): 5733, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593794

RESUMO

In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe3+) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Portadores de Fármacos/química , Exossomos/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Compostos de Benzilideno/farmacologia , Compostos de Benzilideno/uso terapêutico , Linhagem Celular Tumoral/transplante , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/imunologia , Exossomos/imunologia , Exossomos/metabolismo , Feminino , Ferroptose/imunologia , Humanos , Ácido Hialurônico/química , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Melanoma Experimental/imunologia , Melanoma Experimental/patologia , Camundongos , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Evasão Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia
15.
Orthop Surg ; 13(7): 2119-2126, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34636160

RESUMO

OBJECTIVE: To evaluate the outcomes of locked posterior shoulder dislocation with reverse Hill-Sachs lesions in patients treated with anatomical reconstructions. METHODS: Patients who were treated at our institution between January 2016 and June 2020 were retrospectively reviewed. The demographics of the patients including gender, age, occupation, and dominant arm were recorded. Eleven cases from 10 patients qualified in this study. Nine males and one female were included. The mean age of the patients was 44.8 years (range, 33-54 years). Mechanism of injury, duration between injuries and definitive diagnosis, misdiagnosis, size of humeral head impaction, treatment maneuver, and details of operation performed were reviewed. Plain radiographs and computed tomography (CT) scan were taken to determine the size of defects preoperatively and fracture healing during follow-up. During surgery, the deltopectoral approach was employed. Anatomical reconstruction procedure including reduction, disimpaction, bone grafting, and fixation were sequentially performed. Either cancellous autograft from iliac crest or allograft were used and the fractures were anatomically reduced and stabilized by screws or plates. Visual Analog Scale (VAS) and Constant-Murley score were recorded to determine the functional outcomes preoperatively, at 3 months and 6 months postoperatively, and at the last follow-up. The range of motion in forward flexion was recorded at 6 months follow-up postoperatively. RESULTS: Causes of injuries included epileptic seizure in four cases, fall in three cases, and road traffic accident in three cases. Misdiagnoses occurred in five out of 10 patients. The mean time between injury and definitive treatment among those misdiagnosed was 112 days. The mean size of the impacted reverse Hill-Sachs lesions was 33.95% (range, 19.1%-42.6%). All patients received surgical management with anatomical reconstruction approach, including open reduction, disimpaction, bone grafting, and internal fixation. The mean amount of bleeding during operation was 450 mL. The mean follow-up period was 22.6 months. Fracture healing was observed by 8 weeks in all cases postoperatively and evidence of bone grafting could not be further detected on CT scan at 6 month during follow-up. VAS was significantly lower at the last follow-up (0.68 ± 0.21) in comparison to preoperative scores (4.96 ± 0.97) (P < 0.05). Constant-Murley was improved significantly at the last follow-up (91.7 ± 8.3) in comparison to that preoperatively (40.6 ± 10.3) (P < 0.05). The mean range of motion in forward flexion was 38.25° ± 9.36° preoperatively and significantly improved to 162.48° ± 12.68° at 6-month follow-up (P < 0.05). CONCLUSION: The anatomical reconstruction procedure by open reduction and bone augmentation for the treatment of locked posterior shoulder dislocation with reverse Hill-Sachs lesion was promising in both fracture healing and functional outcomes.


Assuntos
Lesões de Bankart/cirurgia , Transplante Ósseo/métodos , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Luxação do Ombro/cirurgia , Adulto , Aloenxertos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ossos Pélvicos/transplante , Estudos Retrospectivos , Inquéritos e Questionários
16.
Niger J Clin Pract ; 24(10): 1531-1534, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34657021

RESUMO

Background: Nasal septum perforation (NSP) is an anatomical defect of the mucosa, cartilage/bone of nasal septum and septoplasty is the most common cause of it. A perforated septum rarely heals on its own, it is more likely to get worse. The success for large perforations is approximately 78%, it is harder to be successful in vertically larger perforations. We introduce a new technique to close large perforations by the fascia lata and costal cartilage sandwich graft (FLSG). The main advantage of this technique is that the fascia lata eliminates the opening between the septal mucosal flaps in case the septal mucosal flaps may not meet each other. Patients and Methods: 16 cases presenting with nasal septum perforation were repaired with the FLSG technique. Grafts were harvested, the perforation was accessed through open rhinoplasty approach, FLSG is inserted and sutured. Results: 16 cases consisting of 9 males (56.25%) and 7 females (43.75%) were operated. The age range was between 20 and 43 years (mean 32.6 ± 6.94). 3 cases (18.75%) had medium and 13 cases (81.25%) had large NSP. 8 cases (50%) were smokers. Nine month postoperatively, all medium NSP were closed. During this period, 14 NSP (87.5%) medium size NSP achieved complete closure, while the remaining two NSP that were yet to close had large defects (>2 cm) and smokers. Conclusion: FLSG is an effective, easy, and novel technique in NSP repair and the postoperative controls have proven a high success rate even in large NSP.


Assuntos
Cartilagem Costal , Perfuração do Septo Nasal , Adulto , Fascia Lata/transplante , Feminino , Humanos , Masculino , Perfuração do Septo Nasal/cirurgia , Septo Nasal/cirurgia , Estudos Retrospectivos , Adulto Jovem
17.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638612

RESUMO

Hypoparathyroidism is an endocrine disorder characterized by low serum calcium levels, high serum phosphorus levels, and by inappropriate or absent secretion of the parathyroid hormone (PTH). The most common therapeutic strategy to treat this condition is hormone replacement therapy with calcium and vitamin D but, unfortunately, in the long term this treatment may not be sufficient to compensate for the loss of endocrine function. Glandular autotransplantation is considered the most effective technique in place of replacement therapy. Although it leads to excellent results in most cases, autotransplantation is not always possible. Allograft is a good way to treat patients who have not been able to undergo autograft, but this technique has limited success due to side effects related to tissue rejection. This therapy is supported by systemic immunosuppression, which leads to the onset of serious side effects in patients, with a risk of endocrine toxicity. Today, research on endocrine disorders is focused on discovering alternative graft therapies that can allow optimal results with the fewest possible side effects. In this review, we will make an update on the current state of the art about the cell and tissue therapy as treatment for hypoparathyroidism, to identify which type of therapeutic strategy could be valid for a future clinical use.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Hipoparatireoidismo/terapia , Animais , Encapsulamento de Células , Terapia Baseada em Transplante de Células e Tecidos/tendências , Humanos , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/fisiopatologia , Glândulas Paratireoides/citologia , Glândulas Paratireoides/transplante , Medicina Regenerativa , Transplante de Células-Tronco , Transplante Autólogo , Transplante Homólogo
18.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34638840

RESUMO

BACKGROUND: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). METHODS: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. RESULTS: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. CONCLUSIONS: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.


Assuntos
Atrofia Geográfica , Células-Tronco Pluripotentes Induzidas , Epitélio Pigmentado da Retina , Animais , Antígenos de Diferenciação/biossíntese , Modelos Animais de Doenças , Regulação da Expressão Gênica , Atrofia Geográfica/metabolismo , Atrofia Geográfica/patologia , Atrofia Geográfica/cirurgia , Xenoenxertos , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Epitélio Pigmentado da Retina/transplante , Suínos
19.
Anticancer Res ; 41(10): 4741-4751, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593423

RESUMO

BACKGROUND/AIM: Heat shock protein 105 (HSP105) is overexpressed in various cancers, but not in normal tissues. We investigated the expression levels of HSP105 in cervical cancer and the efficacy of immunotherapy targeting HSP105. MATERIALS AND METHODS: Previously, we established human leukocyte antigen-A*02:01 (HLA-A2) restricted HSP105 peptide-specific cytotoxic T lymphocyte (CTL) clones from a colorectal cancer patient vaccinated with an HSP105 peptide. Herein, we evaluated the expression of HSP105 in cervical cancer and cervical intraepithelial neoplasia. Moreover, we tested the effectiveness of an HLA-A2-restricted HSP105 peptide-specific CTL clone against cervical cancer cell lines. RESULTS: HSP105 was expressed in 95% (19/20) of examined cervical cancer tissues. Moreover, the HSP105 peptide-specific CTL clone recognized HSP105- and HLA-A*02:01-positive cervical cancer cell lines and also showed that cytotoxicity against the cervical cancer cell lines depends on HSP105 peptide and HLA class I restricted manners. CONCLUSION: HSP105 could be an effective target for immunotherapy in patients with cervical cancer.


Assuntos
Proteínas de Choque Térmico HSP110/imunologia , Imunoterapia/métodos , Neoplasias do Colo do Útero/terapia , Animais , Linhagem Celular Tumoral , Feminino , Antígeno HLA-A2/imunologia , Antígeno HLA-A2/metabolismo , Proteínas de Choque Térmico HSP110/metabolismo , Humanos , Camundongos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/transplante , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Artigo em Inglês | MEDLINE | ID: mdl-34672143

RESUMO

Aortic valve neocuspidization with fixed autologous pericardium according to the Ozaki technique has been proven to be an effective therapy for the treatment of aortic valvulopathies of various entities (aortic stenosis, aortic regurgitation, aortic valve endocarditis) in both tricuspid and bicuspid aortic valves. Thus, aortic valve neocuspidization with fixed autologous pericardium represents a versatile alternative to complex aortic valve repair, with better hemodynamics compared to biological aortic valve replacement and without the need for lifelong anticoagulation, which characterizes mechanical aortic valve replacement. The authors meticulously describe all the technical steps of this highly reproducible, standardized procedure.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Humanos , Pericárdio/transplante , Resultado do Tratamento
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