Zielstellung: Die optimale Ernährung kritisch kranker internistischer Patienten ist noch immer Gegenstand von Diskussionen. Es ist unklar, welche Energiemenge in Bezug auf den Krankheitsverlauf und den klinischen Ausgang günstig ist. Das Anliegen der vorliegenden Arbeit bestand darin, während der ersten sieben Tage der akuten Krankheitsphase eine normokalorische mit einer nur 50% des ermittelten Energiebedarfes abdeckenden künstlichen Ernährung bezüglich klinischer und metabolischer Parameter zu vergleichen. Methode: Es wurden kritisch kranke internistische Patienten, die länger als drei Tage eine künstliche Ernährung benötigten, innerhalb der ersten 24 Stunden nach Aufnahme auf der Intensivstation in die Studie eingeschlossen und in zwei Studienarme randomisiert. Die Patienten der Gruppe 1 erhielten 100%; Patienten der Gruppe 2 nur 50% des ermittelten täglichen Energiebedarfes. Ergebnisse: Insgesamt wurden 100 Patienten eingeschlossen (54 in Gruppe 1 und 46 in Gruppe 2). Es waren 66 Männer und 34 Frauen mit einem durchschnittlichen Alter von 65,8±11,6 Jahren. In der hypokalorisch ernährten Gruppe befanden sich signifikant mehr Diabetiker, jedoch war der Insulinbedarf in der normokalorisch ernährten Gruppe signifikant höher. Die gastrointestinale Toleranz war in der hypokalorisch ernährten Gruppe signifikant besser als in der normokalorischen Gruppe. In der hypokalorischen Gruppe wurden nosokomiale Infektionen häufiger beobachtet als in der normokalorischen Gruppe. Bezüglich des Überlebens auf der Intensivstation, im Krankenhaus und am Tag 28 ergaben sich keine signifikanten Unterschiede zwischen den Ernährungsregimen. Es gab keine Korrelation zwischen Energie- und Proteinzufuhr und klinischem Ausgang. Schlussfolgerungen: Während der ersten sieben Tage ist eine hypokalorische Ernährung bei kritisch kranken internistischen Patienten mit einem geringeren Insulinbedarf und einer besseren gastrointestinalen Verträglichkeit verbunden. Die Rate an nosokomialen Infektionen war allerdings unter hypokalorischer Ernährung höher, wobei in Bezug auf den klinischen Ausgang kein Unterschied zwischen den Gruppen beobachtet wurde. Die vorliegende Studie sollte allerdings aufgrund der relativ geringen Fallzahl als eine Pilotstudie angesehen werden.

Researchers examining clinically-relevant trends for sexual minority women have found evidence of psychological distress and greater utilization of mental health services compared to heterosexually-identified women. However, the results of many research studies with this population have methodological limitations surrounding recruitment of participants, cross-sectional methods, and participant report of clinical services utilized. Few researchers have sought to analyze actual clinical presentation, service utilization, or clinical outcome of sexual minority women in a treatment-setting. This study is an in-depth clinical analysis of 215 sexual minority woman who sought services at a large Midwestern university counseling center over a period of two years and nine months. The analyses conducted allowed for the initial clinical presentation, service utilization, and clinical outcome of sexual minority women to be described and compared to comparative samples of service-seeking female college students. Sexual minority women were found to have a greater incidence of prior suicidality and prior counseling compared to heterosexual women at the same agency. Sexual minority women also reported greater symptoms of social anxiety, eating concerns, and family distress than heterosexual women at the same agency. Of seven examined predictors of service utilization, sexual minority identity label, age, and academic term of service initiation differentiated brief and extended service utilization from moderate service utilization. Prior use of counseling, psychological distress, racial-ethnic minority status, and time in the semester of initiation of services were not significant predictors of service utilization. Implications and limitations of these findings are presented, and future directions for research and intervention are discussed.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13029号 / 論医博第2111号 / 新制||医||1016(附属図書館) / 32987 / (主査)教授 大森 孝一, 教授 別所 和久, 教授 坂井 義治 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No / To assess the technical success rate, and evaluate the clinical outcome, length of hospital stay, and cost of palliative gastro-duodenal stenting in a single-centre. Materials and methods Eight-seven patients referred for insertion of a gastroduodenal stent between April 1999 and April 2004 were recruited to a non-randomized, before and after intervention study performed in a single centre. Demographic data, diagnosis and symptoms along with clinical and technical outcomes were recorded. Results The technical success rate was 84/87 (96.6%), with inability to traverse the stricture in three patients. No immediate complications were demonstrated. There was marked improvement after stent placement with resolution of symptoms and commencement of dietary intake in 76 patients (87%). Stenting resulted in improved quality of life as reflected by an increase in Karnofsky score from 44/100, to 63/100 post-procedure. Late complications included perforation (n=1), migration (n=1) and stent occlusions due to tumour ingrowth/overgrowth (n=7; mean 165 days). Mean survival was 107 days (range 0¿411 days). Median hospital stay post-stent placement was 5.5 days, (range 1¿55 days) with a majority of patients (75%) discharged home. The mean cost of each treatment episode was £4146 ($7132 $US, ¿6,028 EUROS). Conclusion The present series confirms that combined endoscopic and radiological gastroduodenal stenting is a highly favourable treatment for patients with inoperable malignant gastric outlet obstruction. The results suggest that this minimally invasive procedure has a very high technical success rate, whilst at the same time providing excellent palliation of symptoms with improved quality of life in the majority of patients.

Advances in high-throughput genomic and proteomic technology have led to a growing interest in cancer biomarkers. These biomarkers can potentially improve the accuracy of cancer subtype prediction and subsequently, the success of therapy. However, identification of statistically and biologically relevant biomarkers from high-throughput data can be unreliable due to the nature of the data--e.g., high technical variability, small sample size, and high dimension size. Due to the lack of available training samples, data-driven machine learning methods are often insufficient without the support of knowledge-based algorithms. We research and investigate the benefits of using knowledge-based algorithms to solve clinical prediction problems. Because we are interested in identifying biomarkers that are also feasible in clinical prediction models, we focus on two analytical components: feature selection and predictive model selection. In addition to data variance, we must also consider the variance of analytical methods. There are many existing feature selection algorithms, each of which may produce different results. Moreover, it is not trivial to identify model parameters that maximize the sensitivity and specificity of clinical prediction. Thus, we introduce a method that uses independently validated biological knowledge to reduce the space of relevant feature selection algorithms and to improve the reliability of clinical predictors. Finally, we implement several functions of this knowledge-based method as a web-based, user-friendly, and standards-compatible software application.

[Truncated abstract] Hyaline articular cartilage is a highly specialised tissue consisting of chondrocytes embedded in a matrix of proteoglycan and collagens. Hyaline articular cartilage withstands high levels of mechanical stress and continuously renews its extracellular matrix. Despite this durability, mature articular cartilage is vulnerable to injury and disease processes that cause irreparable tissue damage. Native hyaline articular cartilage has poor regenerative capacity following injury, largely due to the tissue's lack of blood and lymphatic supply, as well as the inability of native chondrocytes to migrate through the dense extracellular matrix into the defect site. Articular cartilage injuries that fail to penetrate the subchondral bone plate evoke only a short-lived metabolic and enzymatic response, which fails to provide sufficient new cells or matrix to repair even minimal damage. Clinically, it has previously been accepted that treatment of such defects does not result in the restoration of normal hyaline articular cartilage, which is able to withstand the mechanical demands that are placed on the joint during every day activities of daily living. ... Historically, rehabilitation following ACI has not kept pace with the advances in cell culture and surgical technique. Subsequently, there exists a significant gap in knowledge regarding `best practice' in post operative rehabilitation following ACI. The importance of structured rehabilitation in ACI should not be underestimated when evaluating the clinical success of this chondral treatment. Patients should not be left to their own devices following ACI surgery, as the risk of damage to their implant (via delamination) is high if immediate postoperative movement is not controlled. Furthermore, the biological longevity and clinical success of the graft is dependent on a controlled and graduated return to ambulation and physical activity, and the biomechanical stimulation of the implanted chondrocytes.

Zielstellung: Die optimale Ernährung kritisch kranker internistischer Patienten ist noch immer Gegenstand von Diskussionen. Es ist unklar, welche Energiemenge in Bezug auf den Krankheitsverlauf und den klinischen Ausgang günstig ist. Das Anliegen der vorliegenden Arbeit bestand darin, während der ersten sieben Tage der akuten Krankheitsphase eine normokalorische mit einer nur 50% des ermittelten Energiebedarfes abdeckenden künstlichen Ernährung bezüglich klinischer und metabolischer Parameter zu vergleichen. Methode: Es wurden kritisch kranke internistische Patienten, die länger als drei Tage eine künstliche Ernährung benötigten, innerhalb der ersten 24 Stunden nach Aufnahme auf der Intensivstation in die Studie eingeschlossen und in zwei Studienarme randomisiert. Die Patienten der Gruppe 1 erhielten 100%; Patienten der Gruppe 2 nur 50% des ermittelten täglichen Energiebedarfes. Ergebnisse: Insgesamt wurden 100 Patienten eingeschlossen (54 in Gruppe 1 und 46 in Gruppe 2). Es waren 66 Männer und 34 Frauen mit einem durchschnittlichen Alter von 65,8±11,6 Jahren. In der hypokalorisch ernährten Gruppe befanden sich signifikant mehr Diabetiker, jedoch war der Insulinbedarf in der normokalorisch ernährten Gruppe signifikant höher. Die gastrointestinale Toleranz war in der hypokalorisch ernährten Gruppe signifikant besser als in der normokalorischen Gruppe. In der hypokalorischen Gruppe wurden nosokomiale Infektionen häufiger beobachtet als in der normokalorischen Gruppe. Bezüglich des Überlebens auf der Intensivstation, im Krankenhaus und am Tag 28 ergaben sich keine signifikanten Unterschiede zwischen den Ernährungsregimen. Es gab keine Korrelation zwischen Energie- und Proteinzufuhr und klinischem Ausgang. Schlussfolgerungen: Während der ersten sieben Tage ist eine hypokalorische Ernährung bei kritisch kranken internistischen Patienten mit einem geringeren Insulinbedarf und einer besseren gastrointestinalen Verträglichkeit verbunden. Die Rate an nosokomialen Infektionen war allerdings unter hypokalorischer Ernährung höher, wobei in Bezug auf den klinischen Ausgang kein Unterschied zwischen den Gruppen beobachtet wurde. Die vorliegende Studie sollte allerdings aufgrund der relativ geringen Fallzahl als eine Pilotstudie angesehen werden.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially curative treatment option for patients who have resectable disease is surgery either liver resection (LR) or liver transplantation (LT). When performed in a context of aggressive therapy, long-term outcomes after surgery, particularly liver resection for FL-HCC, were favorable. The clinical outcome of patients with unresectable disease is suboptimal with median survival of less than 12 months. The aim of this review is to update the available evidence on diagnosis, treatment options, outcome predictors, and recent developments of patients with this rare disease and to provide a summarized overview of the available literature.

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially curative treatment option for patients who have resectable disease is surgery either liver resection (LR) or liver transplantation (LT). When performed in a context of aggressive therapy, long-term outcomes after surgery, particularly liver resection for FL-HCC, were favorable. The clinical outcome of patients with unresectable disease is suboptimal with median survival of less than 12 months. The aim of this review is to update the available evidence on diagnosis, treatment options, outcome predictors, and recent developments of patients with this rare disease and to provide a summarized overview of the available literature.

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early- and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS.