京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22303号 / 医博第4544号 / 新制||医||1040(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 福原 俊一, 教授 川口 義弥, 教授 松村 由美 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

1 Abstract Aim: To evaluate the diagnostic performance of FDG PET/CT in the detection of stent graft infection (SGI) with the use of visual and semiquantitative interpretation, to compare it with standalone CT analysis, to verify the transferability of the experience with FDG PET/CT in surgical prosthesis infection and to define the role of the method in the diagnostic algorithm of SGI. Subjects and Methods: In this retrospective study, two nuclear medicine physicians have independently analyzed 21 FDG PET/CT examinations performed in 20 subjects (16 men, 66 ± 8 years) between 2010 and 2019 for clinical suspicion of SGI. Six subjects examined from other reasons without signs of infection constituted a control group. The images were evaluated for the uptake pattern and intensity, and by the maximum standard uptake value (SUVmax), the target-to-background ratio with blood pool (TBRBP) and liver uptake (TBRhep) as a reference. The SGI was defined as the presence of focal hyperactivity with an intensity exceeding hepatic uptake. CT images were independently assessed for signs of SGI. Clinical review of all further patients' data served as the standard of reference. Results: Twelve cases were established as SGI by the clinical review. PET/CT correctly diagnosed SGI in eight and yielded a sensitivity of 92 % and...

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No description available.

Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003–2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36–23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28–52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011–1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091–4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001–1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/μL on POD 7 (OR 16.1 (95% CI: 1.31–195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97–63.18), p = 0.048), NK cells < 125 cells/μL on POD 3 (OR 6.97 (95% CI: 3.81–12.7), p < 0.01), basophils < 18.1 cells/μL on POD 10 (OR 3.45 (95% CI: 1.37–12.3), p = 0.02) and mDC < 4.7 cells/μL on POD 7 (OR 11.68 (95% CI: 1.85–73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect and—by diligent clinical management—even prevent deteriorated outcome due to IRI and eRGI after KT.

Synthetic vascular grafts are useful to bypass diseased arteries. The long-term failure of synthetic grafts is primarily due to intimal hyperplasia at the anastomotic sites. The accelerated intimal hyperplasia may stem from a compliance mismatch between the host artery and the graft since commercially available synthetic conduits are much stiffer than an artery. The objective of this thesis is to design a method for fabricating a vascular graft that mechanically matches the patients native artery over the expected physiologic range of pressures. The creation of an optimized mechanical graft will hopefully lead to an improvement in patency rates. The mechanical equivalency between the graft and the host artery is defined locally by several criteria including the diameter upon inflation, the elasticity at mean pressure, and axial force. A single parameter mathematical for a thin-walled tube is used to describe of the final mechanical behavior of a synthetic graft. For the general problem, the objective would be to fabricate a mechanics-matching vascular graft for each host artery. Typically, fabrication parameters are set initially and the properties of the fabricated graft are measured. However, by modeling the entire fabrication process and final mechanical properties, it is possible to invert the situation and let the typical output mechanical values be used to define the fabrication parameters. The resultant fabricated graft will then be mechanically matching. As a proof-of-concept, several prototype synthetic grafts were manufactured and characterized by a single Invariant to match a canine artery. The resultant graft equaled the diameter upon inflation, the elasticity at mean pressure, and axial force of the native canine artery within 6%. An alternative to making an individual graft for each artery is also presented. A surgeon may choose the best graft from a set of pre-manufactured grafts, using a computer program algorithm for best fit using two parameters in a neighborhood. The design optimization problem was solved for both canine carotid and human coronary arteries. In conclusion, the overall process of design, fabrication and selection of a mechanics matching synthetic vascular graft is shown to be reliable and robust.

A reconstrução dos maxilares em implantodontia através de métodos de enxertia óssea constitui o procedimento cirúrgico mais utilizado frente à perda fisiológica ou traumática a que estes ossos estão sujeitos. Os enxertos autógenos mostram vantagens em relação às demais técnicas de reconstrução no que se refere ao potencial regenerador ósseo, entretanto, a sua remoção implica obrigatoriamente na necessidade de áreas doadoras. Nas últimas décadas tem ocorrido um grande interesse pelos enxertos alógenos de banco de tecidos músculo-esquelético (BTME) como alternativa às enxertias autógenas, como forma de evitar morbidade do sítio doador e redução de tempo e custos da cirurgia. O propósito do estudo foi comparar o comportamento dos enxertos alógenos com autógenos avaliados por métodos imunohistoquímicos, histológicos e tomográficos. Trinta e seis coelhos da linhagem New Zealand White foram submetidos a cirurgias para enxertia &Prime;onlay&Prime; de osso autógeno (grupo controle) e osso alógeno em lados diferentes da mandíbula de forma aleatória. Seis animais de cada grupo foram sacrificados aos 03, 05, 07, 10, 20 e 60 dias após as cirurgias. Cortes histológicos foram corados com Tricrômio de Mallory para as análises histológicas. As imuno marcações foram realizadas com osteoprotegerina (OPG); receptor activator of nuclear factor-k&beta; ligand (RANKL); fosfatase alcalina (ALP); osteopontina (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); colágeno tipo I (Col I) e osteocalcina (OC). A manutenção do volume e densidade dos enxertos foi avaliada por meio de tomografias obtidas após as cirurgias e após os sacrifícios. Os enxertos autógenos e alógenos exibiram padrões de preservação de volume e densidade similares; os dados histológicos mostram que a remodelação óssea no grupo alógeno ocorreu de modo mais intenso que no grupo autógeno; a avaliação por microscopia de luz mostra que a incorporação do osso autógeno ao leito receptor foi mais eficiente que no grupo alógeno; no grupo alógeno os resultados de imunohistoquímica demonstraram um quadro típico de intensa remodelação dos enxertos. / The reconstruction of jaws in implantology using methods of bone grafting constitutes is becoming the most popular surgical procedure due to the physiologic bone loss that follows teeth extraction or trauma. The autogenous grafts show advantages in relation to the other reconstruction techniques because its potential as bone regenerator. However, its removal implicates obligatorily in the areas donor areas. In the last decades aroused the interest for the bone bank (BTME) as alternative to the autogenous grafting, as a manner to avoid donor sites morbidity and reduction of time and surgery costs. The purpose of the study was to compare the behavior of allografts with autogenous using methods of immunochemistry, histology and tomography. Thirty six rabbits of the lineage New Zealand White were submitted to surgeries for onlay grafting of autogenous bone (group control) and allogenous bone randomly placed bilaterally in the mandible. Six animals of each group were sacrificed to the 03, 05, 07, 10, 20 and 60 days after the surgeries. Paraffin sections were stained with Mallorys Trichrome for histologics analyses. Immuno labeling accomplished with osteoprotegerin (OPG); receptor activator of nuclear factor-k&beta; ligand (RANKL); alkaline fosfatase (ALP); osteopontin (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); collagen type I (COL I) and osteocalcin (OC). The maintenance of the volume and density of the grafts was evaluated on tomographs obtained after surgeries and sacrifices. The autogenous grafts and allografts exhibited patterns of volume preservation and similar density; the histological data show that the remodelation bone in the group allograft happened in a more intense way than in the autogenous group; the evaluation for light microscopic shows that the incorporation of the autogenous bone on donors bed was more efficient than in the allogenous group; in the allogenous group for immunohistochemical results demonstrated a typical picture of intense remodelation of the grafts.

Meine Untersuchungen zeigen, dass es sich bei der zellfreien DNA (cfDNA, engl. cell-free DNA) des Spenderorgans (GcfDNA, engl. graft-derived cell-free DNA) um einen klinisch vielversprechenden Biomarker zur direkten Ermittlung der Organschädigung im Sinne einer „flüssigen Biopsie“ handelt. Alles was dafür notwendig ist, ist eine Blutprobe des Empfängerpatienten. Im Gegensatz zu konventionellen Markern wird die Organschädigung unmittelbar, direkt und hochspezifisch angezeigt. Durch neue Entwicklungen in der Labordiagnostik lässt sich dieser Marker im routinemäßigen Einsatz mittels digital droplet PCR (ddPCR) bestimmen. Die Analyseergebnisse können bei verhältnismäßig niedrigen Kosten innerhalb eines Arbeitstages erstellt werden. Unmittelbar nach Transplantation ist bei allen Patienten eine sehr hohe Konzentration der GcfDNA messbar. Innerhalb von wenigen Tagen fallen die Werte schnell ab und erreichen die Größenordnung stabiler Transplantatempfänger, die in der Lebertransplantation unter 10% liegen. Dabei besteht keine signifikante Korrelation der initialen GcfDNA-Freisetzung mit der Ischämieschädigung des Spenderorgans, ermittelt durch die Dauer der kalten Ischämiezeit (WIZ). Bei unzureichender Immunsuppression ist eine erhöhte GcfDNA-Freisetzung zu beobachten. Mithilfe der GcfDNA als Marker der Organintegrität lässt sich auch der gemeinsame Effekt verschiedener Immunsuppressiva ermitteln. Die GcfDNA verhält sich dabei umgekehrt proportional zur immunsuppressiven Therapie. Patienten mit akuten Abstoßungen haben im Mittel GcfDNA-Werte oberhalb von 50%. Die GcfDNA-Werte sind bereits mehrere Tage vor einer klinisch manifestierten akuten Abstoßung erhöht. Auch eine virusassoziierte Transplantatschädigung durch Hepatitis C manifestiert sich in vergleichsweise höheren GcfDNA-Werten. Cholestasen gehen hingegen nicht mit erhöhten GcfDNA-Werten einher. Die immunsuppressive Therapie könnte sich durch den routinemäßigen Einsatz der GcfDNA sicherer, einfacher, zuverlässiger und individueller gestalten lassen. Unter-Immunsuppressionen und daraus resultierende Abstoßungen würden sich bereits in der subklinischen Phase erkennen lassen und die Therapie von der bloßen Reaktion auf klinische Ereignisse hin zur Prävention verschieben. Um das Ziel einer personalisierten Medizin zu erreichen, könnte die Immunsuppression für jeden Patienten auf das absolut notwendige und damit gegenüber der bisherigen Praxis optimale Maß festgelegt werden. Geringere Nebenwirkungen und eine Reduktion der Kosten für das Gesundheitswesen wären die Konsequenz. Dieser Marker könnte dazu beitragen, das finale Ziel, nämlich eine Verbesserung des Langzeiterfolges nach Organtransplantationen, zu erreichen. Multizentrische Studien zur Validierung dieses Markers vor dem routinemäßigen Einsatz laufen bereits.

A reconstrução dos maxilares em implantodontia através de métodos de enxertia óssea constitui o procedimento cirúrgico mais utilizado frente à perda fisiológica ou traumática a que estes ossos estão sujeitos. Os enxertos autógenos mostram vantagens em relação às demais técnicas de reconstrução no que se refere ao potencial regenerador ósseo, entretanto, a sua remoção implica obrigatoriamente na necessidade de áreas doadoras. Nas últimas décadas tem ocorrido um grande interesse pelos enxertos alógenos de banco de tecidos músculo-esquelético (BTME) como alternativa às enxertias autógenas, como forma de evitar morbidade do sítio doador e redução de tempo e custos da cirurgia. O propósito do estudo foi comparar o comportamento dos enxertos alógenos com autógenos avaliados por métodos imunohistoquímicos, histológicos e tomográficos. Trinta e seis coelhos da linhagem New Zealand White foram submetidos a cirurgias para enxertia &Prime;onlay&Prime; de osso autógeno (grupo controle) e osso alógeno em lados diferentes da mandíbula de forma aleatória. Seis animais de cada grupo foram sacrificados aos 03, 05, 07, 10, 20 e 60 dias após as cirurgias. Cortes histológicos foram corados com Tricrômio de Mallory para as análises histológicas. As imuno marcações foram realizadas com osteoprotegerina (OPG); receptor activator of nuclear factor-k&beta; ligand (RANKL); fosfatase alcalina (ALP); osteopontina (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); colágeno tipo I (Col I) e osteocalcina (OC). A manutenção do volume e densidade dos enxertos foi avaliada por meio de tomografias obtidas após as cirurgias e após os sacrifícios. Os enxertos autógenos e alógenos exibiram padrões de preservação de volume e densidade similares; os dados histológicos mostram que a remodelação óssea no grupo alógeno ocorreu de modo mais intenso que no grupo autógeno; a avaliação por microscopia de luz mostra que a incorporação do osso autógeno ao leito receptor foi mais eficiente que no grupo alógeno; no grupo alógeno os resultados de imunohistoquímica demonstraram um quadro típico de intensa remodelação dos enxertos. / The reconstruction of jaws in implantology using methods of bone grafting constitutes is becoming the most popular surgical procedure due to the physiologic bone loss that follows teeth extraction or trauma. The autogenous grafts show advantages in relation to the other reconstruction techniques because its potential as bone regenerator. However, its removal implicates obligatorily in the areas donor areas. In the last decades aroused the interest for the bone bank (BTME) as alternative to the autogenous grafting, as a manner to avoid donor sites morbidity and reduction of time and surgery costs. The purpose of the study was to compare the behavior of allografts with autogenous using methods of immunochemistry, histology and tomography. Thirty six rabbits of the lineage New Zealand White were submitted to surgeries for onlay grafting of autogenous bone (group control) and allogenous bone randomly placed bilaterally in the mandible. Six animals of each group were sacrificed to the 03, 05, 07, 10, 20 and 60 days after the surgeries. Paraffin sections were stained with Mallorys Trichrome for histologics analyses. Immuno labeling accomplished with osteoprotegerin (OPG); receptor activator of nuclear factor-k&beta; ligand (RANKL); alkaline fosfatase (ALP); osteopontin (OPN); vascular endothelial growth factor (VEGF); tartrate-resistant acid phosphatase (TRAP); collagen type I (COL I) and osteocalcin (OC). The maintenance of the volume and density of the grafts was evaluated on tomographs obtained after surgeries and sacrifices. The autogenous grafts and allografts exhibited patterns of volume preservation and similar density; the histological data show that the remodelation bone in the group allograft happened in a more intense way than in the autogenous group; the evaluation for light microscopic shows that the incorporation of the autogenous bone on donors bed was more efficient than in the allogenous group; in the allogenous group for immunohistochemical results demonstrated a typical picture of intense remodelation of the grafts.

Title: Physical therapy procedures in patients following the operation of the anterior cruciate ligament Objectives: The main objective of this work is to determine the influence of the chosen method of reconstruction and subsequent physiotherapy on the final status of the patient. And also if the group physiotherapy is the ideal therapeutic approach. Methods: In quantitative research the numerical analysis of the data was performed. Comparison of individual groups was performed simply through finding the frequency distribution of individual characters. Evaluated were the basic sets A (patients operated on by Bone - Tendon - Bone method, BTB) and B (patients operated on by hamstring graft method, STG). Both sets were assessed using the input and the output kinesiological analysis. The resulting values of the variables in each category (individual examinations in the input and output kinesiological analysis) were compared with each other.The statistical significance of observed differences was tested using the x2 (chi square) test at the significance level of p < 0.05. Results: It was determined that the selected surgical method (BTB and STG) has an effect on certain parameters evaluated in the input rated kinesiological analysis. These parameters in the majority of examinations performed at the...