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Dive into the research topics where Klaus-Martin Schulte is active.

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Featured researches published by Klaus-Martin Schulte.


Oncologist | 2011

Castleman's Disease: Systematic Analysis of 416 Patients from the Literature

Nadia Talat; Klaus-Martin Schulte

BACKGROUND Castlemans disease is a rare primary disease of the lymph nodes with limited available clinical information. METHODS A systematic literature search identified 416 cases amenable to detailed analysis. RESULTS In HIV(-) patients, centricity, pathology type, the presence of symptoms, gender, and age all predict outcome in univariate analyses. The 3-year disease-free survival (DFS) rate for patients with unicentric hyaline vascular disease (49.5% of cases, class I) was 92.5%, versus 45.7% for those with multicentric plasma cell disease (20.2% of cases, class III) and 78.0% for those with any other combination (22.6% of cases, class II) (p < .0001). HIV(+) patients (class IV) exclusively presented with multicentric plasma cell disease and had a 3-year DFS rate of only 27.8%. Kaposis sarcoma and lymphoma were observed in 59.3% and 9.4% of HIV(+) patients and in 2.6% and 3.6% of HIV(-) patients (p < .0001). Paraneoplastic pemphigus and the syndrome of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes were observed exclusively in HIV(-) patients at a rate of 1.3% and 1.8%, respectively. CONCLUSION Clinical, pathological, and viral markers allow for the classification of Castlemans disease into groups with markedly different outcomes and disease associations.


Proceedings of the National Academy of Sciences of the United States of America | 2014

Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance.

Antonios Chatzigeorgiou; Tom Seijkens; Barbara Zarzycka; David Engel; Marjorie Poggi; Susan M. van den Berg; Sjoerd A. A. van den Berg; Oliver Soehnlein; Holger Winkels; Linda Beckers; Dirk Lievens; A. Driessen; Pascal Kusters; Erik A.L. Biessen; Ruben Garcia-Martin; Anne Klotzsche-von Ameln; Marion J. J. Gijbels; Randolph J. Noelle; Louis Boon; Tilman M. Hackeng; Klaus-Martin Schulte; Aimin Xu; Gert Vriend; Sander B. Nabuurs; Kyoung-Jin Chung; Ko Willems van Dijk; Patrick C. N. Rensen; Menno P.J. de Winther; Norman L. Block; Andrew V. Schally

Significance Inflammation is a critical contributor to the pathogenesis of metabolic disorders associated with obesity. A group of molecules crucial in regulating the immune system are costimulatory molecules, including CD40. Our current study shows that CD40 acts as a double-edged sword in the metabolic syndrome through the initiation of differential signaling cascades. The CD40-TNF receptor-associated factor (TRAF) 2/3/5 signaling pathway protects against metabolic dysfunction and inflammation associated with obesity; conversely, the CD40-TRAF6 pathway contributes to the detrimental consequences of obesity. In the present study, we therefore designed, validated, and used a small-molecule inhibitor that blocks CD40-TRAF6 interactions. The improvement of insulin resistance by this specific CD40-TRAF6 inhibitor could represent a therapeutic breakthrough in the field of immunometabolism. The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40−/− mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8+ T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII+ cells exhibited a similar phenotype in DIO as CD40−/− mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII+ cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII+ cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII+ cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance.


Clinical Endocrinology | 2012

Lateral cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging-guided and prophylactic removal of the lateral compartment.

Mubashir Mulla; Wolfram T. Knoefel; Jackie Gilbert; Alan McGregor; Klaus-Martin Schulte

Papillary thyroid cancer (PTC) is a common endocrine cancer and frequently presents with lymph node (LN) metastases. The frequency of LN metastases in the lateral compartment and their surgical removal are poorly defined. There are no prospective randomised controlled trials addressing an eventual outcome difference relating to the extent of the initial surgical approach. The aim of this study was to define the extent of lateral LN involvement and the role of imaging in identification of these metastatic LN.


Nature Reviews Clinical Oncology | 2010

Castleman's disease—a two compartment model of HHV8 infection

Klaus-Martin Schulte; Nadia Talat

Castlemans disease is a primary infectious disease of the lymph node that causes local symptoms or a systemic inflammatory syndrome. Histopathology reveals a destroyed lymph node architecture that can range from hyaline-vascular disease to plasma-cell disease. Viral interleukin 6 (vIL-6) produced during the replication of human herpesvirus type 8 (HHV8) is the key driver of systemic inflammation and cellular proliferation. Stage progression of Castlemans disease results from switches between viral latency and lytic replication, and lymphatic and hematogenous spread. Multicentric plasma-cell disease in HIV-1 patients is associated with HHV8 infection. Polyclonal plasmablast proliferation escapes control in the germinal center with eventual malignant transformation into non-Hodgkin lymphoma. Surgery produces excellent results in unicentric disease, while multicentric disease responds to anti-CD20 therapy or IL-6 and chemotherapy. Lymphovascular endothelium and naive B cells are infectious reservoir-opening options for antiangiogenic and anti-CD19 strategies to enhance outcomes in patients with systemic disease.


Nature Reviews Endocrinology | 2012

Diagnosis and management of parathyroid cancer

Klaus-Martin Schulte; Nadia Talat

Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any individual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.


Clinical Endocrinology | 2012

Central cervical lymph node metastases in papillary thyroid cancer

Mubashir Mulla; Klaus-Martin Schulte

Background  Papillary thyroid cancer (PTC) is a common endocrine cancer and commonly presents with lymph node (LN) metastases. The role of surgical removal of the central cervical LN compartment is poorly defined. There are no prospective randomized controlled trials addressing the relevance to the extent of the initial surgical approach.


World Journal of Surgery | 2010

Lymph Node Involvement and Surgical Approach in Parathyroid Cancer

Klaus-Martin Schulte; Nadia Talat; John Miell; Caje Moniz; Prakash Sinha; Salvador Diaz-Cano

BackgroundThe best surgical approach to parathyroid cancer is disputed. Recommendations vary and are built on incoherent evidence. High rates of recurrence and death require an in-depth review of underlying findings.MethodsThis retrospective study includes 11 patients with parathyroid cancer who underwent surgery with central and/or lateral neck dissection by a single surgeon between 2005 and 2010. The diagnosis was based on histopathological criteria in all patients. Patterns of lymph node and soft tissue involvement of these and formerly reported patients were analysed based on full-text review of all published cases of parathyroid cancer.ResultsIn this series only 1 of 11 patients (9.1%) manifested lymph node metastasis. In the literature, lymph node metastases have been reported in only 6.5% of 972 published patients, or in 32.1% of the 196 in whom lymph node involvement was assessed by the authors. They were, with few exceptions, localised in the central compartment. Recurrence in soft tissue is more frequent than in locoregional lymph nodes.ConclusionOncological en bloc clearance of the central compartment with meticulous removal of all possibly involved soft tissues, including a systematic central lymph node resection, may improve outcomes and should be included in the routine approach to the suspicious parathyroid lesion. There is no need for a prophylactic lateral neck dissection.


Surgery | 2008

The -1082 interleukin-10 polymorphism is associated with acute respiratory failure after major trauma: A prospective cohort study

Ove Schroeder; Klaus-Martin Schulte; Julia Schroeder; Axel Ekkernkamp; Reinhold Alexander Laun

BACKGROUND Acute respiratory failure is a common, life-threatening complication after severe trauma. Polymorphisms in cytokine genes, linked to cytokine inducibility, may influence the susceptibility to acute respiratory failure and serve as risk predictors. METHODS This PROSPECTIVE cohort study (n = 100) included Caucasian multiple trauma (Injury Severity Score [ISS] >15) patients at a level 1 trauma center in Berlin, Germany. Primary outcome measure acute respiratory failure was defined as a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio of <200 and the need for mechanical respiratory support. We investigated the association of polymorphisms of the interleukin (IL)-1beta, IL-6, and IL-10 genes with acute respiratory failure. RESULTS Of 100 patients with severe mechanic injury (median ISS 34, interquartile range 19-45), 49 developed acute respiratory failure. Acute respiratory failure frequency differed significantly with the IL-10 -1082 genotype (P = .007; P corrected, .03), whereas there was no significant relation to any other cytokine genotype after Bonferroni correction for multiple testing. The -1082 GG genotype was a marker of decreased risk to develop acute respiratory failure in univariate (odds ratio [OR], 0.2; 95% confidence interval [CI], 0.1-0.6; P = .004) and multivariate (OR, 0.2; 95% CI, 0.1-0.9; P = .03) logistic regression analysis, with male gender, severe abdominal injury, and an APACHE II score >19 being significant risk factors. CONCLUSION We conclude that the IL-10 -1082 genotype may be a risk marker for development of acute respiratory failure after trauma.


World Journal of Emergency Surgery | 2009

Small bowel haemorrhage associated with partial midgut malrotation in a middle-aged man

Ajay P. Belgaumkar; Dheeraj Karamchandani; Praveen Peddu; Klaus-Martin Schulte

We describe a case of life-threatening small bowel haemorrhage in a 56 year old man, who was found to have partial midgut malrotation at laparotomy. An association between congenital malrotation and gastrointestinal haemorrhage has not previously been reported in this age group. We discuss the association between gut malrotation and small intestinal pathology and describe the principles of management in these patients.


The Journal of Clinical Endocrinology and Metabolism | 2010

The Clinical Spectrum of Multiple Endocrine Neoplasia Type 2a Caused by the Rare Intracellular RET Mutation S891A

Klaus-Martin Schulte; Andreas Machens; Laura Fugazzola; Alan McGregor; Salvador Diaz-Cano; Louise Izatt; Simon Aylwin; Nadia Talat; Paolo Beck-Peccoz; Henning Dralle

BACKGROUND Germline missense mutations of the RET protooncogene cause a clinical spectrum called multiple endocrine neoplasia (MEN) type 2. A strong genotype-phenotype correlation results in major implications for the clinical approach. More information on less common mutations is needed to advance specific guidance. PATIENTS AND METHODS We report individualized patient information on 36 carriers of the intracellular RET gene mutation S891A from three centers and clustered data of 38 former patients reported in the literature in nine additional studies. RESULTS S891A mutation accounts for up to 5% of all patients to date reported with RET mutations and 16% of those hitherto reported with intracellular mutations. S891A mutation caused medullary thyroid cancer (MTC) in 69.4%, pheochromocytoma in 2.8%, and parathyroid hyperplasia in 8.3% of the 36 patients of this case series and in 63.5, 4.1, and 4.1%, respectively, for the entire groups of 74 patients. The youngest age of onset for MTC in this group was 17 yr (median, 46 yr; range, 17-80 yr), for pheochromocytoma 46 yr (median, 46 yr), and for parathyroid hyperplasia 17 yr (median, 20 yr, range, 17-46 yr). Persistence of MTC was described in 14.3% of patients with available follow-up. Additional findings included corneal nerve thickening in three of 74 patients (4.1%). CONCLUSION This intracellular mutation can initiate the full spectrum of MEN2a, initiates MTC at an early age, and causes recurrence and death if undertreated. We recommend stringent adherence to established guidance in MEN2a in this rare mutation.

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Nadia Talat

University of Cambridge

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Dylan Lewis

University of Cambridge

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Ben Whitelaw

University of Cambridge

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