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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.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
Curr Opin Organ Transplant ; 26(6): 654-659, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653086

RESUMO

PURPOSE OF REVIEW: Murine studies have established that uterine natural killer (uNK) cells are critical regulators of normal placentation and fetal development in mammals. However, the biology of uNK cells in humans remains poorly understood. This ignorance represents a costly knowledge gap, as disordered placentation is thought to underpin a variety of pregnancy complications that impact maternal and neonatal health. In the context of uterus transplantation (UTx), uNK cells are anticipated to play a critical role within the allograft. Here, we review the current understanding of uNK cells in pregnancy biology and explore how this critically important cell population may contribute to pregnancy and graft outcomes in uterus transplant recipients. RECENT FINDINGS: Recent studies have characterized differences in NK cell populations between anatomic compartments in humans. In the endometrium, at least five phenotypically and functionally distinct subpopulations of uNK cells have been identified, with research into mechanisms regulating their differentiation and function currently underway. SUMMARY: Further elucidating uNK cell biology has the potential to influence the outcomes of pregnancy and UTx and benefit human health. UTx is a unique opportunity to study uNK cell biology and may shed light on mechanisms by which immunological tolerance is established at the maternal-fetal interface.


Assuntos
Células Matadoras Naturais , Útero , Animais , Feminino , Humanos , Tolerância Imunológica , Camundongos , Gravidez , Útero/transplante
9.
Ann Plast Surg ; 87(5): 542-546, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34699433

RESUMO

BACKGROUND: Reinforcement of the abdominal wall with synthetic mesh in autologous breast reconstruction using abdominal free tissue transfer decreases the risk of bulging and herniation. However, the impact of the plane of mesh placement on donor site complications has not yet been investigated. METHODS: We performed a retrospective analysis of 312 patients who had undergone autologous breast reconstruction with muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flaps or deep inferior epigastric perforator (DIEP) flaps as well as polypropylene mesh implantation at the donor site. Donor site complications were compared among patients with different flap types and different mesh positions including overlay (n = 90), inlay and overlay (I-O; n = 134), and sublay (n = 88). RESULTS: Abdominal hernias occurred in 2.86% of patients who had undergone MS-TRAM reconstructions and in 2.63% of patients who had undergone DIEP reconstructions. When comparing patients with different mesh positions, donor site complications occurred in 14.4% of patients with overlay mesh, 13.4% of patients with I-O mesh, and 10.2% of patients with sublay mesh (P = 0.68). Abdominal hernias occurred in 4.44% of patients with overlay mesh, 2.24% of patients with I-O mesh, and 2.27% of patients with sublay mesh (P = 0.69). Multivariable logistic regression analysis did not identify a significant association between mesh position and hernia rates as well as wound complications. CONCLUSIONS: Our data indicate that the plane of synthetic mesh placement in relation to the rectus abdominis muscle does not impact the rate of postoperative donor site complications in patients undergoing breast reconstruction with MS-TRAM or DIEP flaps.


Assuntos
Parede Abdominal , Mamoplastia , Retalho Perfurante , Artérias Epigástricas/cirurgia , Humanos , Mamoplastia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Reto do Abdome/transplante , Estudos Retrospectivos , Telas Cirúrgicas/efeitos adversos
10.
Curr Opin Organ Transplant ; 26(6): 634-639, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34714790

RESUMO

PURPOSE OF REVIEW: Uterus transplantation (UTx) is transitioning from an experimental procedure to a clinical treatment for absolute uterine factor infertility (AUFI). Standardized protocols for the evaluation and selection of donors and recipients that maximize chances of success - a healthy live birth - are needed. RECENT FINDINGS: To date, recipient eligibility has been limited to otherwise healthy women with AUFI who are of childbearing age and are good candidates for in-vitro fertilization (IVF). For donors (living or deceased), selection criteria vary, apart from basic requirements of blood-type compatibility and freedom from critical infectious diseases, but generally require a term birth and a uterus free from uterine pathologies. The stepwise evaluation process for candidate recipients and living donors moves through health screening (medical and psychosocial); initial selection committee review; IVF (recipients only); and final selection committee review. This eliminates candidates with poor chances of success before exposure to unnecessary risks. SUMMARY: The currently stringent selection criteria for prospective recipients and donors will likely broaden, as UTx becomes more widely available. Continued research is needed to define the donor, recipient and uterine graft factors associated with successful outcomes, and to support the development of standardized selection criteria.


Assuntos
Infertilidade Feminina , Transplante de Órgãos , Feminino , Humanos , Infertilidade Feminina/cirurgia , Doadores Vivos , Transplante de Órgãos/efeitos adversos , Seleção de Pacientes , Útero/transplante
11.
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
12.
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
13.
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
14.
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
15.
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
16.
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
17.
PLoS One ; 16(10): e0257457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34679077

RESUMO

OBJECTIVE: An evidence regarding which bony flap for reconstruction of mandibular defects following tumour resection is associated with the highest survival rate is still lacking. This network meta-analysis (NMA) aimed to guide surgeons selecting which vascularized osseous flap is associated with the highest survival rate for mandibular reconstruction. METHODS: From inception to March 2021, PubMed, Embase, Scopus, and Cochrane library were searched to identify the eligible studies. The outcome variable was the flap survival rate. The Bayesian NMA accompanied by a random effect model and 95% credible intervals (CrI) was calculated. RESULTS: Twenty-two studies with a total of 1513 patients, comparing four osseous flaps namely fibula free flap (FFF), deep circumferential iliac artery flap (DCIA), scapula flap, and osteocutaneous radial forearm flap (ORFF) were included. The respective survival rates of FFF, DCIA, Scapula, and ORFF were 94.50%, 93.12%, 97%, and 95.95%. The NMA failed to show a statistically significant difference between all comparators (FFF versus DCIA (Odd ratio, 1.8; CrI, 0.58,5.0); FFF versus ORFF (Odd ratio, 0.57; CrI, 0.077; 2.9); FFF versus scapula flap (Odd ratio, 0.25; CrI, 0.026; 1.5); DCIA versus ORFF (Odd ratio, 0.32; CrI, 0.037; 2.1); DCIA versus scapula flap (Odd ratio, 0.14; CrI, 0.015; 1.1) and ORFF versus scapula flap (Odd ratio, 2.3; CrI, 0.16; 34)). CONCLUSION: Within the limitations of the current NMA, FFF, DCIA, Scapula, and ORFF showed a comparable survival rate for mandibular reconstruction. Although the scapula flap reported the highest survival rate compared to other osseous flaps for mandibular reconstruction; however, the decision making when choosing an osseous flap should be based on many factors rather than simply flap survival rate.


Assuntos
Retalhos de Tecido Biológico , Reconstrução Mandibular/métodos , Neoplasias Ósseas/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Retalhos de Tecido Biológico/transplante , Humanos , Mandíbula/cirurgia , Metanálise em Rede , Escápula/irrigação sanguínea , Escápula/transplante
18.
J Immunol Methods ; 498: 113133, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34480950

RESUMO

The study of the effect of cryopreservation on the functionality of monocyte-derived dendritic cells (MDDCs) and dendritic cells (DCs) is essential for their use in different clinical applications such as DCs-based vaccines. Its full maturation and its optimal functionality are crucial for DCs based immunotherapy. In this study, we compared MDDCs derived from fresh and cryopreserved PBMCs in the aspects of phenotype and its effect on T cells at the level of proliferation and cytokine secretion. We pulsed MDDCs obtained from fresh and cryopreserved PBMCs with two different stimuli, CEF and SEA, and the expression maturation markers and cytokine secretion were analyzed. Our results showed that the cryopreservation had no effects in the phenotype of the MDDCs obtained, cell viability, maturation markers expression and/or cytokines secretion, independently whether MDDCs had been generated from fresh or cryopreserved PBMCs. Thus, this study suggests that the use of cryopreserved cells is a good method to keep the cells before use in immunotherapy, avoiding the variability within same individual due to severe blood draws. Even so, the interpretation and comparison of different results should be done considering the different cryopreservation techniques and assays, and their effects on PBMCs, specifically on MDDC and DC cells.


Assuntos
Diferenciação Celular , Criopreservação , Células Dendríticas/imunologia , Monócitos/imunologia , Vacinas/imunologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Estudos de Viabilidade , Citometria de Fluxo , Humanos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Fenótipo , Linfócitos T/imunologia , Linfócitos T/metabolismo
19.
Am J Physiol Lung Cell Mol Physiol ; 321(5): L872-L884, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34523355

RESUMO

The influenza virus infection poses a serious health threat worldwide. Myeloid cells play pivotal roles in regulating innate and adaptive immune defense. A disintegrin and metalloproteinase (ADAM) family of proteins contributes to various immune responses; however, the role of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) in influenza virus infection remains largely unknown. Herein, we investigated its role, focusing on myeloid cells, during influenza virus infection in mice. ADAM10 gene (Adam10)flox/flox/Lyz2-Cre (Adam10ΔLyz2) and control Adam10flox/flox mice were intranasally infected with 200 plaque-forming units of influenza virus A/H1N1/PR8/34. Adam10ΔLyz2 mice exhibited a significantly higher mortality rate, stronger lung inflammation, and a higher virus titer in the lungs than control mice. Macrophages and inflammatory cytokines, such as TNF-α, IL-1ß, and CCL2, were increased in bronchoalveolar lavage fluid from Adam10ΔLyz2 mice following infection. CD11b+Ly6G-F4/80+ myeloid cells, which had an inflammatory monocyte/macrophage-like phenotype, were significantly increased in the lungs of Adam10ΔLyz2 mice. Adoptive transfer experiments suggested that these cells likely contributed to the poorer prognosis in Adam10ΔLyz2 mice. Seven days after infection, CD11b+Ly6G-F4/80+ lung cells exhibited significantly higher arginase-1 expression levels in Adam10ΔLyz2 mice than in control mice, whereas an arginase-1 inhibitor improved the prognosis of Adam10ΔLyz2 mice. Enhanced granulocyte-macrophage colony-stimulating factor (GM-CSF)/GM-CSF receptor signaling likely contributed to this process. Collectively, these results indicate that myeloid ADAM10 protects against influenza virus pneumonia and may be a promising therapeutic target.


Assuntos
Proteína ADAM10/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Arginase/biossíntese , Vírus da Influenza A Subtipo H1N1/metabolismo , Macrófagos/imunologia , Proteínas de Membrana/metabolismo , Células Mieloides/imunologia , Infecções por Orthomyxoviridae/patologia , Proteína ADAM10/genética , Transferência Adotiva/métodos , Secretases da Proteína Precursora do Amiloide/genética , Animais , Arginase/antagonistas & inibidores , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/análise , Imunidade Inata/imunologia , Macrófagos/transplante , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/transplante , Infecções por Orthomyxoviridae/mortalidade , Infecções por Orthomyxoviridae/prevenção & controle , Prognóstico , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo
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