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1.
Nephrol Dial Transplant ; 38(9): 2052-2066, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-36662032

RESUMO

BACKGROUND: Although obesity has become a significant problem in transplantation medicine, the impact of different immunosuppressive protocols on clinical outcomes in obese transplant recipients remains unclear. METHODS: We performed an analysis of the Scientific Registry of Transplant Recipients database. Kidney transplant recipients were categorized according to body mass index (BMI) categories and immunosuppressive protocols: (i) tacrolimus/mycophenolate mofetil (Tac-MMF), (ii) mTOR-inhibitor/Tac (mTORi-Tac), (iii) mTORi/cyclosporin (mTORi-Cyc) and (iv) mTORi-MMF. RESULTS: Graft recipients with advanced obesity (BMI ≥35 kg/m2) exhibited significantly lower rates of acute rejection during the first year after transplantation in the mTORi-Tac (6.4%) group compared with Tac-MMF (11.2%). Obesity class 1 (30 < BMI < 35 kg/m2) was associated with a significant risk of acute rejection for the mTORi-Tac group [obesity class 1 hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.21-2.62, P = .003]. A similar trend was observed in the Tac-MMF group for advanced obesity HR 1.29; 95% CI 0.96-1.73, P = .087). For the Tac-MMF group, recipients with both overweight and obesity had significantly impaired survival due to cardiovascular events and also increased mortality due to infection in advanced obesity. Combination of mTORi and calcineurin inhibitor was associated with lower rejection rates and stable long-term kidney function while reducing cardiovascular side effects linked to calcineurin inhibitors in obese kidney graft recipients. CONCLUSION: These results are critical for the growing number of obese graft recipients and warrant prospective evaluation.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Transplantados , Pontuação de Propensão , Sirolimo/uso terapêutico , Imunossupressores/efeitos adversos , Tacrolimo/uso terapêutico , Inibidores de Calcineurina/uso terapêutico , Ácido Micofenólico/uso terapêutico , Obesidade/complicações , Obesidade/cirurgia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto , Quimioterapia Combinada
2.
Eur Spine J ; 32(4): 1187-1195, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36856867

RESUMO

PURPOSE: Adolescent idiopathic scoliosis (AIS) often correspond with hypo thoracic kyphosis (TK) or even lordosis. The aim of this study was to analyze the influence of posterior instrumentation in thoracic AIS. METHODS: Analysis of prospectively collected AIS-data with structural thoracic curves (Lenke type 1 & 2), operated 2010-2019 with pedicle screw dual rod systems in one scoliosis center. Follow-up (FU) minimum 24 months. Coronal and sagittal angles measured based on standing long-cassette-X-rays: thoracic major (MC), proximal thoracic (PC) and lumbar curve (LC), TK, lumbar lordosis (LL). STATISTICAL ANALYSIS: values as mean ± SD, differences by student's t-test (significancy a = 0.05), Pearson's correlation, sub-analysis with sagittal modifier (-, N, +). RESULTS: A total of 127 AIS could be identified (63% type 1, 37% type 2). Mean FU 32.2 ± 16.6 months, mean age 14 ± 1.5 years. Mean Correction of MC 73 ± 12%, PC 51 ± 17%, LC 69 ± 21% with a significantly better correction of PC in Lenke 2 curves(p < 0.05). On average, TK (FU-preop) decreased by -2.1 ± 12.1°(p < 0.05) in all AIS. Whereas TK in type 1 was unchanged (p = 0.9), TK significantly decreased by - 6.0 ± 12.7°(p < 0.05) in type 2. No significant difference in LL. TK in hypokyphotic cases increased by 9.5 ± 5.5°(p < 0.05), stayed almost unchanged (- 1.4 ± 9.1°,p = 0.2) in normokyphotic, decreased by - 17.2 ± 14.2°(p < 0.05) in hyperkyphotic cases. Only hypokyphotic cases had a moderately strong correlation between correction of LC (r = 0.6) and PC (r = - 0.4) (frontal plane) and change from pre- to postoperative TK (sagittal plane) (r = 0.6). No relevant correlations for normo- and hyperkyphotic AIS. Postoperative hypokyphosis was significantly more often in Lenke 2 (16.3% vs. 2.6%, p < 0.05). Rod diameter (5,5 mm versus 6 mm) had no significant influence. CONCLUSION: Significant correction of hypo- and hyperkyphosis can be achieved with posterior spinal fusion (pedicle screw dual rod systems), whereas normokyphotic spines stay unchanged. However, Lenke 2 curves have a significantly higher risk for a postoperative thoracic hypokyphosis.


Assuntos
Cifose , Lordose , Parafusos Pediculares , Escoliose , Fusão Vertebral , Adolescente , Humanos , Criança , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Lordose/diagnóstico por imagem , Lordose/cirurgia , Seguimentos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Cifose/diagnóstico por imagem , Cifose/cirurgia , Estudos Retrospectivos
3.
Eur Spine J ; 32(9): 3140-3148, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37470846

RESUMO

PURPOSE: In surgical treatment of adolescent idiopathic scoliosis (AIS), only a few studies measure both, radiological parameters and PROMs and correlate them. METHODS: Prospectively collected AIS-data of one scoliosis-center within a multicenter German-Spine-Society-Study. All patients underwent instrumented posterior spinal correction and fusion with pedicle-screw-dual-rod-systems from 05/2019 to 01/2021. The data were retrospectively analyzed. INCLUSION CRITERIA: age 11-17 years, follow-up (FU) at least 12 months. Clinical data, radiographic parameters, and PROMs (SRS-30-questionnaire) were collected. 100% of patients had X-ray images, 88.2% completed SRS-30. Parameters were given as mean ± SD. Differences and subdivision by lower instrumented vertebra (LIV) were analyzed by students t-test (significancy a = 0.05), associations by Pearson's correlation. RESULT: Total of 51 patients: 15 ± 1.4 years, BMI 20.7 ± 3.7 kg/m2, FU 16.6 ± 6.1 months, fusion length 9.2 ± 2.3 segments, implant density 93 ± 9%, surgical time 215 ± 71 min, mean blood loss 504 ± 360 ml. Mean preoperative Cobb angle of main curve 64 ± 14°, of secondary main curve 46 ± 12°, corrected by 68 ± 11%, 56 ± 17%, respectively. Mean thoracic rib and lumbar hump significantly decreased by - 8.5 ± 7.0° and - 7.7 ± 8.9° (p < 0.5). High thoracic rib hump almost unchanged, - 0.4 ± 2.8° (p = 0.3). Thoracic kyphosis (- 0.9 ± 12.8°, p = 0.6), lumbar lordosis (1.5 ± 10.1°, p = 0.3), clavicle angle (- 0.5 ± 2.7°) and spinopelvic parameters (p > 0.5) did not significantly change, only LIV-tilt from 24.5 ± 6.7° to 6.5 ± 4.3° (p < 0.05). PROMs significantly improved (p < 0.05), no significant improvement for function/activity (p = 0.4). Preoperative mean total-score was 3.6 ± 0.5, 4.2 ± 0.3 at FU(p < 0.05). Self-image improved in 67%. Moderately strong correlation for PROMs: the better LIV-tilt (r = - 0.5) correction and the shorter surgery time (r = - 0.4), the better SRS-30 total-score. No correlation for curve correction and patient's satisfaction. CONCLUSION: In summary, results of this study demonstrate good surgical correction and significant improvement of most PROMs.


Assuntos
Cifose , Parafusos Pediculares , Escoliose , Fusão Vertebral , Humanos , Adolescente , Criança , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Satisfação do Paciente , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Fusão Vertebral/métodos , Cifose/cirurgia
4.
Am J Transplant ; 22(2): 402-413, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34551205

RESUMO

Obesity initiates a chronic inflammatory network linked to perioperative complications and increased acute rejection rates in organ transplantation. Bariatric surgery is the most effective treatment of obesity recommended for morbidly obese transplant recipients. Here, we delineated the effects of obesity and bariatric surgery on alloimmunity and transplant outcomes in diet-induced obese (DIO) mice. Allograft survival was significantly shorter in DIO-mice. When performing sleeve gastrectomies (SGx) prior to transplantation, we found attenuated T cell-derived alloimmune responses resulting in prolonged allograft survival. Administering taurodeoxycholic acid (TDCA) and valine, metabolites depleted in DIO-mice and restored through SGx, prolonged graft survival in DIO-mice comparable with SGx an dampened Th1 and Th17 alloimmune responses while Treg frequencies and CD4+ T cell-derived IL-10 production were augmented. Moreover, in recipient animals treated with TDCA/valine, levels of donor-specific antibodies had been reduced. Mechanistically, TDCA/valine restrained inflammatory M1-macrophage polarization through TGR5 that compromised cAMP signaling and inhibited macrophage-derived T cell activation. Consistently, administering a TGR5 agonist to DIO-mice prolonged allograft survival. Overall, we provide novel insights into obesity-induced inflammation and its impact on alloimmunity. Furthermore, we introduce TDCA/valine as a noninvasive alternative treatment for obese transplant patients.


Assuntos
Transplante de Coração , Obesidade Mórbida , Aloenxertos , Animais , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ácido Taurodesoxicólico , Valina
5.
Zentralbl Chir ; 147(4): 354-360, 2022 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-35863355

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic has led to restrictions in surgical care worldwide and therefore also posed new challenges to liver surgery. The respective procedures often entail high perioperative risks and resource requirements. However, the indication for liver surgery is frequently without alternatives. To date, there is little knowledge about the impact of the pandemic on liver surgery in Germany. METHODS: A retrospective data analysis of liver surgery procedures in Germany as well as transplantations was conducted. Evaluations were based on procedure codes recorded between 2010 and 2020 according to diagnosis-related groups (DRG) by the Federal Statistical Office of Germany (Destatis) and data from the German Organ Procurement Organization (Deutsche Stiftung Organtransplantation; DSO). RESULTS: According to DRG procedure codes relating to liver surgery recorded between 2010 and 2020 in Germany, the annual fluctuation for the first year of the pandemic 2020 remained comparable to previous years. Furthermore, the development of post-mortem liver transplantations as well as living liver donations remained stable in Germany in 2020 and 2021. CONCLUSIONS: The number of liver surgery procedures in Germany was subject to a dynamic development until 2020, without apparent changes in the first year of the SARS-CoV-2 pandemic. The most frequently performed liver procedures, as well as liver transplantations, remained stable with respect to their annually recorded numbers. Publication of data regarding procedures in liver surgery and transplantation in 2021 need to be awaited and analyzed to evaluate whether the observations presented in this article prove stable any further.


Assuntos
COVID-19 , Transplante de Fígado , COVID-19/epidemiologia , Alemanha , Humanos , Fígado , Pandemias , Estudos Retrospectivos , SARS-CoV-2
6.
Acta Orthop Belg ; 88(3): 457-466, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36791698

RESUMO

Postoperative shoulder imbalance (PSI) is a common complication following adolescent idiopathic scolio- sis (AIS) surgery. There is little data available in literature on prediction of PSI. Prospectively collected data of AIS with thoracic curve (Lenke 2), operated in 2014-2018 at a single scoliosis-center, were analyzed retrospectively using X-rays of whole spine and traction films (TA): age, Cobb-angle of proximal (PC), major thoracic (MC) and lumbar curve (LC), shoulder height [mm], clavicle angle [°], T1-tilt [°], plumb line [mm]. Results as mean ± standard deviation. Change over time (postOP- FU) compared using t-test (≥=0.05). Correlation of preOP parameters and curve correction with PSI (|≥|15mm) was analyzed by correlation (Pearson)- and regression-classification-analysis. 32 AIS, average age of 14±1.3 yrs. FU 16 months (84%). Curve correction was 52.5% (PC), 70.1% (MC), 69.9% (LC), significant change in FU for PC (-2.4°, p>0.05), not for MC, LC (p=0.2, p=0.6). Shoulder height was negative if right- side up: 2.9±15.1mm (preOP), 5.5±15.0 mm (TA), 17.9±14.9mm (postOP), 17.4±8.4mm (FU). 28% had preOP shoulder imbalance, 69% postOP and 44% FU had PSI. Shoulder height on TA correlated to change preOP to FU (r=0.62) and preOP shoulder height (r=-0.85), clavicle angle had strong correlation (r=- 0.81). Regression-classification-analysis: correction of MC>62.4%, 81.5% of cases had PSI; with correction of MC>64.9% and LC>93.2%, 51.9% of cases had PSI. PSI is a common in Lenke2 AIS. In preOP planning TA, shoulder position and clavicle angle should be considered to prevent PSI. Correction of MC should be moderate, overcorrection of the LC avoided.


Assuntos
Escoliose , Fusão Vertebral , Humanos , Adolescente , Criança , Ombro/cirurgia , Escoliose/cirurgia , Estudos Retrospectivos , Vértebras Torácicas/cirurgia , Clavícula , Fusão Vertebral/métodos
7.
Am J Transplant ; 21(2): 488-502, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32717114

RESUMO

Elderly organ transplant recipients have remained underrepresented in clinical trials, despite representing a rapidly growing population. Here, we assessed age-specific effects of CTLA4-Ig (cytotoxic T-lymphocyte antigen 4-Ig), a fusion protein blocking costimulatory signaling between antigen-presenting cells and T cells through CD28. Cardiac allografts in young mice (2-3 months) treated with CTLA4-Ig survived indefinitely, whereas 80% of old recipients (18 months) had lost their graft after 100 days. CTLA4-Ig was also significantly less effective in older recipients of skin transplants. CTLA4-Ig reduced CD4+ central memory and effector memory T cells and diminished systemic interferon-gamma levels only in young recipients. These differences corresponded to a reduced expression of CD28 on antigen-experienced CD4+ T cells in old mice. In support, adoptive transfer of old CD4+ T cells that were transfected with a lentiviral vector inducing constant expression of CD28 accelerated the rejection of allogeneic skin grafts in young RAG2-/- recipient mice. Regulatory T cells (Tregs), in contrast, demonstrated an increased expression of CD28 with aging and CTLA4-Ig treatment in old recipients resulted in reduced frequencies, compromised proliferation, and diminished suppressive capacity of Tregs. These findings may prove to have unique clinical consequences for immunosuppression in the growing population of elderly transplant recipients.


Assuntos
Sobrevivência de Enxerto , Imunoconjugados , Abatacepte , Animais , Antígenos CD28 , Antígeno CTLA-4 , Rejeição de Enxerto/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
8.
BMC Gastroenterol ; 21(1): 436, 2021 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-34802417

RESUMO

BACKGROUND: Endoscopic negative pressure therapy is a novel and successful treatment method for a variety of gastrointestinal leaks. This therapy mode has been frequently described for rectal and esophageal leakages. Duodenal diverticular perforations are rare but life-threatening events. The early diagnosis of duodenal diverticular perforation is often complicated by inconclusive symptoms. This is the first report about endoscopic negative pressure therapy in patients with perforated duodenal diverticula. CASE PRESENTATION: We present two cases of duodenal diverticula perforations treated with endoscopic negative pressure therapy as stand-alone treatment. Start of symptoms varied from one to three days before hospital admission. Early sectional imaging led to the diagnosis of duodenal diverticular perforation. Both patients were treated with endoluminal endoscopic negative pressure therapy with simultaneous feeding option. Three respective changes of the suction device were performed. Both patients were treated with antibiotics and antimycotics during their hospital stay and be discharged from hospital after 20 days. CONCLUSIONS: This is the first description of successful stand-alone treatment by endoscopic negative pressure therapy in two patients with perforated duodenal diverticulum. We thus strongly recommend to attempt interventional therapy with endoluminal endoscopic negative pressure therapy in patients with duodenal diverticular perforations upfront to surgery.


Assuntos
Divertículo , Duodenopatias , Úlcera Duodenal , Perfuração Intestinal , Úlcera Péptica Perfurada , Idoso , Idoso de 80 Anos ou mais , Divertículo/complicações , Divertículo/cirurgia , Duodenopatias/complicações , Duodenopatias/cirurgia , Duodeno , Esôfago , Feminino , Humanos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia
9.
Eur Spine J ; 30(5): 1277-1284, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33409727

RESUMO

PURPOSE: The mean potential of lordosis restoration by transforaminal lumbar interbody fusion (TLIF) is supposed to be low in general. In contrast, clinical experience shows a wide range of segmental lordosis correction. In this study, the predictability of lordosis correction should be investigated. METHODS: Prospectively collected register data were analyzed retrospectively. One hundred twenty-one consecutive patients (2014-2016) operated with single-level TLIF L4/5 (10°-lordotic cage). Segmental lordosis (L4/5) and overall lordosis (L1-S1) were measured on lumbar X-rays: preoperatively (pre), after 3-5 days (post), at least 24 months postoperatively (2yFU). Outcome and satisfaction of patients were assessed. Parameters were statistically compared by students t-tests (a = 0.05). In addition, predictors of correction were analyzed. RESULTS: Age was 60.7 years, rate of 2yFU 41.3% (n = 50). Lordosis correction L4/5 was statistically significant with (post-pre) 4.9 ± 5.7° (p < 0.01), but not significant for L1-S1 (post-pre) 1.6 ± 8.0° (p = 0.3). A strong-moderate correlation of lordosis L4/5 (pre) and lordosis correction L4/5 (post-pre) was shown (r = - 0.6, p < 0,01). In a rising range of preoperative lordosis L4/5 from 15-30° the likelihood of lordosis loss increased. In 2yFU correction, L4/5 was significant with (post-pre) 5.4 ± 5.4° (p < 0.01), no significant long-term change (2yFU-postop) - 1.5 ± 4.9° (p = 0.2). No correlation (r = - 0.1) of correction and ODI. VAS-B improved by means of 2.9, VAS-L by 2.5, ODI by 19.1% (pre vs. 2yFU), each statistically significant (p < 0.01). CONCLUSION: Significant segmental relordosation can be performed by TLIF L4/5. The potential of correction strongly correlates with preoperative lordosis. Therefore, TLIF technique should be considered carefully in cases with a preoperative segmental lordosis of more than 15° and additional need of lordosation.


Assuntos
Lordose , Fusão Vertebral , Humanos , Vértebras Lombares , Região Lombossacral , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
10.
Zentralbl Chir ; 146(6): 597-604, 2021 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-34587646

RESUMO

BACKGROUND: The SARS-CoV-2 pandemic has caused an unprecedented global health crisis, with exceptionally high mortality rates in high-risk groups of affected patients. It is alarming that a steadily increasing number of clinical reports on outcomes of COVID-19 in solid organ transplant (SOT) recipients suggests a detrimental impact linked to high overall mortality. However, systematic data on SARS-CoV-2 infections in SOT recipients in Germany are still scarce. MATERIAL AND METHODS: We conducted a survey on SARS-CoV-2 infection status among 387 SOT recipients treated at our centre during the past 5 years - located in a severely affected region in Germany. The survey was sent out two months after the first SARS CoV-2 outbreak in our region had resulted in government-imposed lockdown measures. RESULTS: An incidence rate of 0.4% SARS-CoV-2-positive SOT recipients was determined in our cohort, in line with reported local infection rates in the general population at this time. However, the only SARS CoV-2 infection known to us within this group of patients led to severe morbidity - resulting in prolonged mechanical ventilation, hospitalisation > 60 days and finally in irreversible loss of graft function. CONCLUSION: Our data demonstrate that SOT recipients are at equal risk for SARS-CoV-2 infections when compared to the general population, while SARS-CoV-2 infections in SOT recipients seem to be associated with deleterious clinical consequences.


Assuntos
COVID-19 , Transplante de Órgãos , Controle de Doenças Transmissíveis , Alemanha , Humanos , SARS-CoV-2
11.
Eur Spine J ; 29(8): 2036-2045, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32447530

RESUMO

PURPOSE: In surgical correction of scoliosis with pedicle screw dual-rod systems, frequently used freehand technique of screw positioning is challenging due to 3D deformity. Screw malposition can be associated with serious complications. Image-guided technologies are already available to improve accuracy of screw positioning and decrease radiation to surgeon. This study was conducted to measure intraoperative radiation to patients in freehand technique, evaluate screw-related complications and compare radiation values to published studies using navigation techniques. METHODS: Retrospective analysis of prospectively collected data of 73 patients with idiopathic scoliosis, who underwent surgical correction with pedicle screw dual-rod system. Evaluated parameters were age, effective radiation dose (ED), fluoroscopy time, number of fused segments, correction and complications. Parameters were compared with regarding single thoracic curve (SC) and double thoracic and lumbar curves (DC), adolescent (10-18 years) or adult (> 18 years) idiopathic scoliosis, length of instrumentation. ED was compared with values for navigation from online database. RESULTS: Average age was 21.0 ± 9.7 years, ED was 0.17 ± 0.1 mSv, time of fluoroscopy was 24.1 ± 18.6 s, 9.5 ± 1.9 fused segments. Average correction for SC was 75.7%, for DC 69.9% (thoracic) and 76.2% (lumbar). No screw-related complications. ED was significantly lower for SC versus DC (p < 0.01), short versus long fusions (p < 0.01), no significant difference for age (p = 0.1). Published navigation data showed 6.5- to 8.8-times higher radiation exposure for patients compared to our results. CONCLUSION: Compared to navigation procedures, freehanded positioning of pedicle screws in experienced hands is a safe and effective method for surgical correction of idiopathic scoliosis with a significant decrease in radiation exposure to patients.


Assuntos
Parafusos Pediculares , Exposição à Radiação , Escoliose , Fusão Vertebral , Adolescente , Adulto , Criança , Humanos , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Adulto Jovem
12.
Trends Immunol ; 37(8): 546-556, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27402226

RESUMO

Natural killer (NK) cell receptors (NKRs) play a crucial role in the homeostasis of antigen-experienced T cells. Indeed, prolonged antigen stimulation may induce changes in the receptor repertoire of T cells to a profile that features NKRs. Chronic antigen exposure, at the same time, has been shown to trigger the loss of costimulatory CD28 molecules with recently reported intensified antigen thresholds of antigen-experienced CD8(+) T cells. In transplantation, NKRs have been shown to assist allograft rejection in a CD28-independent fashion. We discuss here a role for CD28-negative T cells that have acquired the competency of the NKR machinery, potentially promoting allorecognition either through T cell receptor (TCR) crossreactivity or independently from TCR recognition. Collectively, NKRs can bring about innate-like T cells by providing alternative costimulatory pathways that gain relevance in chronic inflammation, potentially leading to resistance to CD28-targeting immunosuppressants.


Assuntos
Imunidade Inata , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Imunidade Adaptativa , Envelhecimento/genética , Envelhecimento/imunologia , Envelhecimento/metabolismo , Animais , Antígenos/imunologia , Antígenos CD28/metabolismo , Regulação da Expressão Gênica , Humanos , Terapia de Imunossupressão , Inflamação/genética , Inflamação/imunologia , Inflamação/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Receptores de Antígenos de Linfócitos T , Receptores de Células Matadoras Naturais/genética , Receptores de Células Matadoras Naturais/metabolismo , Transdução de Sinais
13.
Transpl Int ; 31(1): 6-13, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28926127

RESUMO

Alloimmunity traditionally distinguishes short-lived, rapid and nonspecific innate immune responses from adaptive immune responses that are characterized by a highly specific response initiated in a delayed fashion. Key players of innate immunity such as natural killer (NK) cells and macrophages present the first-line defence of immunity. The concept of unspecific responses in innate immunity has recently been challenged. The discovery of pattern recognition receptors (PRRs) has demonstrated that innate immune cells respond in a semi-specific fashion through the recognition of pathogen-associated molecular patterns (PAMPs) representing conserved molecular structures shared by large groups of microorganisms. Although immunological memory has generally been considered as exclusive to adaptive immunity, recent studies have demonstrated that innate immune cells have the potential to acquire memory. Here, we discuss allospecific features of innate immunity and their relevance in transplantation.


Assuntos
Imunidade Inata , Memória Imunológica , Imunologia de Transplantes , Animais , Humanos
14.
BMC Musculoskelet Disord ; 19(1): 10, 2018 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-29316936

RESUMO

BACKGROUND: Degenerative adult de novo (DAD) scoliosis appears characteristically in the sixth or seventh decade with symptoms of severe back pain and radiculopathy or spinal claudication. The aim of this study was to enhance the knowledge of perioperative complications and detect possible risk factors in this selective DAD scoliosis surgery. METHODS: This retrospective study included only patients with DAD scoliosis undergone correction spondylodesis with previous failure of conservative treatment. Excluded were patients with other types of scoliosis and previous fusion surgeries. Patient epidemiological data, medical comorbidities and treatments were included. Intraoperative data and perioperative complications were documented. Analyses regarding early, late and no complications were undertaken. RESULTS: A total of 92 patients with a mean age of 67.29 ± 7.93 years and clinical follow-up visits of minimum 12 months were included. On average, 5.26 ± 2.24 segments were fused. Early complications (e.g. wound healing defects, paresis, screw loosing) occurred in 23 patients and often required a re-operation. Cardiac arrhythmias, pacemaker and coumarin derivative therapies were associated with increased perioperative complications. The transforaminal lumbar interbody fusion technique was associated with early complications. Adjacent segment failure occurred in 36% and was the major late complication. Twenty patients did not have any complications in the minimum follow-up. CONCLUSIONS: This study analysed a selective DAD scoliosis collective and its' surgical treatment outcomes. It identified numerous perioperative complications (adjacent segment failure, postoperative paresis and epidural hematoma) and multiple possible predisposing risk factors (e.g. operative techniques and anti-coagulation therapies). This here gained information raises awareness in preoperative patient selection and preparation. Further studies in DAD scoliosis and a risk-adjusted patient selection/preparation are needed to improve treatment quality and outcomes.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Complicações Pós-Operatórias/etiologia , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Degeneração do Disco Intervertebral/diagnóstico , Masculino , Pessoa de Meia-Idade , Assistência Perioperatória/tendências , Complicações Pós-Operatórias/diagnóstico , Estudos Retrospectivos , Escoliose/diagnóstico , Fusão Vertebral/tendências , Resultado do Tratamento
15.
Circulation ; 132(2): 122-31, 2015 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-25957225

RESUMO

BACKGROUND: Organ transplantation has seen an increased use of organs from older donors over the past decades in an attempt to meet the globally growing shortage of donor organs. However, inferior transplantation outcomes when older donor organs are used represent a growing challenge. METHODS AND RESULTS: Here, we characterize the impact of donor age on solid-organ transplantation using a murine cardiac transplantation model. We found a compromised graft survival when older hearts were used. Shorter graft survival of older hearts was independent of organ age per se, because chimeric young or old organs repopulated with young passenger leukocytes showed comparable survival times. Transplantation of older organs triggered more potent alloimmune responses via intragraft CD11c+ dendritic cells augmenting CD4+ and CD8+ T-cell proliferation and proinflammatory cytokine production, particularly that of interleukin-17A. Of note, depletion of donor CD11c+ dendritic cells before engraftment, neutralization of interleukin-17A, or transplantation of older hearts into IL-17A(-/-) mice delayed rejection and reduced alloimmune responses to levels observed when young hearts were transplanted. CONCLUSIONS: These results demonstrate a critical role of old donor CD11c+ dendritic cells in mounting age-dependent alloimmune responses with an augmented interleukin-17A response in recipient animals. Targeting interleukin-17A may serve as a novel therapeutic approach when older organs are transplanted.


Assuntos
Envelhecimento/imunologia , Antígeno CD11c/imunologia , Células Dendríticas/imunologia , Rejeição de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Interleucina-17/imunologia , Envelhecimento/patologia , Animais , Células Dendríticas/patologia , Rejeição de Enxerto/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Knockout , Transplante Homólogo/efeitos adversos
16.
Eur Spine J ; 25(8): 2359-67, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26363561

RESUMO

Surgery for isthmic and degenerative spondylolisthesis (SL) in adults is carried out very frequently in everyday practice. However, it is still unclear whether the results of surgery are better than those of conservative treatment and whether decompression alone or instrumented fusion with decompression should be recommended. In addition, the role of reduction is unclear. Four clinically relevant key questions were addressed in this study: (1) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with isthmic SL? (2) Is surgery more successful than conservative treatment in relation to pain and function in adult patients with degenerative SL? (3) Is instrumented fusion with decompression more successful in relation to pain and function than decompression alone in adult patients with degenerative SL and spinal canal stenosis? (4) Is instrumented fusion with reduction more successful in relation to pain and function than instrumented fusion without reduction in adult patients with isthmic or degenerative SL? A systematic PubMed search was carried out to identify randomized and nonrandomized controlled trials on these topics. Papers were analyzed systematically in a search for the best evidence. A total of 18 studies was identified and analyzed: two for question 1, eight for question 2, four for question 3, and four for question 4. Surgery appears to be better than conservative treatment in adults with isthmic SL (poor evidence) and also in adults with degenerative SL (good evidence). Instrumented fusion with decompression appears to be more successful than decompression alone in adults with degenerative SL and spinal stenosis (poor evidence). Reduction and instrumented fusion does not appear to be more successful than instrumented fusion without reduction in adults with isthmic or degenerative SL (moderate evidence).


Assuntos
Descompressão Cirúrgica/métodos , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Adulto , Dor nas Costas , Tratamento Conservador , Prática Clínica Baseada em Evidências , Humanos , Vértebras Lombares/cirurgia , Resultado do Tratamento
17.
Orthopade ; 44(2): 138-45, 2015 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-25586505

RESUMO

BACKGROUND: Extreme lateral interbody fusion (XLIF) is an interbody fusion technique, in which access to the lateral part of the disc is achieved via a strong lateral transpsoatic approach. In general, the technique can be applied between T5 and L5. For lumbar segments, neuromonitoring is mandatory to protect the iliolumbar plexus during the psoas passage. OBJECTIVES: In this article, the results regarding use of the XLIF technique are summarized and compared with other anterior and anterolateral approaches. In addition, current publications regarding indication, technique, complications and clinical/radiological outcome measures are discussed. METHODS: The results of a literature review are presented and discussed. RESULTS: Regarding the indication and the surgical options for segmental restoration, the XLIF technique is comparable to anterior or anterolateral and open lateral interbody fusion. The minimally invasive XLIF access promises potentially lower morbidity than open procedures and the risk of injury of the iliac vessels is lower than in anterior and anterolateral approaches. CONCLUSION: Increasing numbers of spine surgeons are using the XLIF method. Current results indicate that XLIF is a safe and reproducible technique for deformities, adjacent level disease, and instability.


Assuntos
Fixadores Internos , Degeneração do Disco Intervertebral/diagnóstico , Degeneração do Disco Intervertebral/cirurgia , Posicionamento do Paciente/métodos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos , Humanos
18.
Curr Opin Organ Transplant ; 20(4): 417-23, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26154914

RESUMO

PURPOSE OF REVIEW: With global demographic changes and an overall improved healthcare, more older end-stage renal disease (ESRD) patients receive kidney transplants. At the same time, organs from older donors are utilized more frequently. Those developments have and will continue to impact allocation, immunosuppression and efforts improving organ quality. RECENT FINDINGS: Findings mainly outside the field of transplantation have provided insights into mechanisms that drive immunosenescence and immunogenicity, thus providing a rationale for an age-adapted immunosuppression and relevant clinical trials in the elderly. With fewer rejections in the elderly, alloimmune responses appear to be characterized by a decline in effectiveness and an augmented unspecific immune response. SUMMARY: Immunosenescence displays broad and ambivalent effects in elderly transplant recipients. Those changes appear to compensate a decline in allospecific effectiveness by a shift towards an augmented unspecific immune response. Immunosuppression needs to target those age-specific changes to optimize outcomes in elderly transplant recipients.


Assuntos
Imunidade Adaptativa , Senescência Celular , Imunidade Inata , Transplante de Rim , Animais , Humanos , Tolerância Imunológica/imunologia , Falência Renal Crônica/cirurgia
19.
J Spinal Disord Tech ; 27(6): 336-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22643187

RESUMO

STUDY DESIGN: Two-arm prospective controlled study. OBJECTIVE: The aim of our study was to prospectively assess the outcome of symptomatic lumbar spinal stenosis (LSS) treated with decompressive surgery alone in comparison with additional implantation of the Coflex interspinous device. SUMMARY OF BACKROUND DATA: In symptomatic LSS, decompression surgery is an established treatment. Recently, a number of interspinous devices have been introduced as an alternative to conventional surgical procedures. The theoretical aim of the Coflex device is to unload the facet joints, restore foraminal height, and provide stability to improve the clinical outcome. Published information is limited, and there are no data that prove the superiority of the implant in comparison with traditional surgical approaches. METHODS: Sixty-two patients with symptomatic LSS were treated with decompressive surgery; 31 of these patients received an additional Coflex device. Preoperatively and postoperatively, disability and pain scores were measured using the Oswestry Disability Index, the Roland-Morris Disability Questionnaire, the Visual Analog Scale, and the pain-free walking distance. Patients underwent postoperative assessments at 3, 6, 12, and 24 month including the above-mentioned scores and patient satisfaction. RESULTS: There was a significant improvement (P<0.001) in the clinical outcome assessed in the Oswestry Disability Index, the Roland-Morris Disability Questionnaire, the Visual Analog Scale, and the pain-free walking distance at all times of reinvestigation compared with the base line in both groups. Up to 2 years after surgery, there were no significant differences between both groups in all ascertained parameters, including the patient satisfaction and subjective operation decision. CONCLUSIONS: The results of this first prospective controlled study indicate that the additional placement of a Coflex interspinous device does not improve the already good clinical outcome after decompressive surgery for LSS in the 24-month follow-up interval.


Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Próteses e Implantes , Estenose Espinal/cirurgia , Idoso , Descompressão Cirúrgica/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estenose Espinal/epidemiologia , Resultado do Tratamento , Caminhada
20.
Orthopadie (Heidelb) ; 52(3): 233-242, 2023 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-36645436

RESUMO

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is often associated with thoracic hypokyphosis or even lordosis. OBJECTIVES: To analyze the influence of posterior correction and fusion in thoracic, structurally double-curved AIS. MATERIAL AND METHODS: Out of 127 thoracic AIS (Lenke types 1 and 2) recorded prospectively, idiopathic double thoracic curve AIS were analyzed retrospectively. Surgery 2010-2019 with pedicle screw double rod systems in a scoliosis center. Follow-up (FU) at least 2 years. Frontal and sagittal angles (whole-spine radiographs, 2 planes): thoracic curve (MK), proximal-thoracic curve (PK) and lumbar curve (LK), thoracic kyphosis (TK), lumbar lordosis (LL). STATISTICAL ANALYSIS: values as MW ± SD, students t­test (significance a = 0.05), Pearson's correlation, sub-analysis with sagittal modifiers (-, N, +). RESULTS: A total of 47 AIS-double thoracic curve were identified, mean FU 29.3 ± 12.2 months, mean age 14 ± 1.5 years. The mean correction (FU-preop) of MK was 67%, PK 53%, LK 73%, each significant, (p < 0.05). On average, TK (FU-preop) decreased by -6.5 ± 11.6° (p < 0.05), no significant change from FU (p = 0.6). TK (FU-preop) increased by 8.6 ± 5.0° (p < 0.05) in hypokyphotic cases, significantly decreased by -4.8 ± 9.6° in normokyphotic AIS and -25.3 ± 11.1° in hyperkyphotic cases, respectively (p < 0.05). In hypokyphosis: moderately strong correlation between correction PK (r = -0.5) and spontaneous correction LK (r = 0.8) (frontal plane) and change from pre- to postop TK (sagittal plane) (p < 0.05). Moderate correlation for hyperkyphosis: correction PK (r = -0.5) and postop TK (p < 0.05). No relevant correlations for normokyphosis. 17% had postop hypokyphosis, of which 0% had preop hypokyphosis. Rod diameter (5.5 mm vs. 6 mm) had no significant effect on TC. CONCLUSIONS: Posterior instrumented correction and fusion (pedicle screw dual rod systems) can significantly correct both lateral curves in idiopathic double thoracic curves, although it is associated with an increased risk of postop thoracic hypokyphosis, especially in preoperatively normokyphotic patients.


Assuntos
Cifose , Lordose , Escoliose , Fusão Vertebral , Humanos , Adolescente , Criança , Escoliose/diagnóstico por imagem , Lordose/etiologia , Estudos Retrospectivos , Vértebras Torácicas/diagnóstico por imagem , Fusão Vertebral/efeitos adversos , Cifose/diagnóstico por imagem , Peróxido de Hidrogênio
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