Dominik Bergis

Prospective Multicenter Study Evaluating Fecal Calprotectin in Adult Acute Bacterial Diarrhea

BACKGROUND Every year, about 2.2 million deaths occur worldwide due to diarrhea. Reliable diagnosis of patients with acute infectious diarrhea remains a formidable challenge to the clinicians. This is the first study reporting use of fecal calprotectin in diagnosing acute diarrhea. The aim was to compare the diagnostic accuracy of fecal calprotectin, fecal lactoferrin, and guaiac-based fecal occult blood test in a diverse group of consecutive patients with acute diarrhea in which routine bacterial stool cultures and cytotoxins for Clostridium difficile were performed. METHODS This was a prospective case-control multicenter study from January 2004 until October 2007 in 2383 consecutive patients with acute diarrhea. They provided stool samples for performing cultures. Patients with positive cultures and an equal number of matched controls with negative cultures underwent fecal occult blood test and calprotectin and lactoferrin assays. RESULTS Calprotectin, lactoferrin, and fecal occult blood tests demonstrated sensitivity and specificity of 83% and 87%, 78% and 54%, and 38% and 85%, respectively, for diagnosing acute bacterial diarrhea. CONCLUSIONS Calprotectin showed high correlation with bacteriologically positive infectious diarrhea compared with lactoferrin and fecal occult blood test. It may potentially revolutionize management algorithm for patients with acute diarrhea. As a screening test, calprotectin can generate results within hours to support presumptive diagnosis of infectious diarrhea, which can decide suitability of stool samples for culture.

Adherence to clinical care guidelines for cystic fibrosis-related diabetes in 659 German/Austrian patients

BACKGROUND In Germany/Austria, data on medical care for cystic fibrosis-related diabetes (CFRD) is limited. METHODS Anonymized data from 659 CFRD patients were analyzed and compared to the latest ADA/CFF guidelines. RESULTS Specialized diabetes clinics were attended less frequently than recommended (3.1 vs. 4.0 times yearly). 7.9% of patients had a complete profile of examinations: diabetes education (44.9%), HbA1c (88.8%), blood pressure (79.5%), BMI (86.5%), lipid status (37.5%), retinopathy (29.9%), microalbuminuria (33.2%), and self-monitoring of blood glucose (71.6%). HbA1c and blood pressure were measured less frequently than recommended (2.3 and 2.0 vs. 4.0 times yearly). Overall, guidelines were followed more frequently in children than adults. Contrary to recommendations, not all patients were treated with insulin (77.2 vs. 100.0%). Insulin therapy was initiated earlier in children than adults, but there was still a substantial delay (0.9 vs. 2.7years after diagnosis, p<0.001). CONCLUSION In CFRD patients studied, adherence to care guidelines was suboptimal.

Psoriasis and Diabetes: A Multicenter Study in 222078 Type 2 Diabetes Patients Reveals High Levels of Depression

Objective. This study aimed to investigate the association between psoriasis and disease outcome in type 2 diabetes (T2D). Methods. 222078 T2D patients (≥10 years old) from the prospective, multicenter diabetes patient registry were analyzed. Specific search items were used to identify psoriasis patients. Multiple regression models were fitted and adjusted for demographic confounder. Results. 232 T2D patients had comorbid psoriasis. After adjusting psoriasis patients revealed a higher BMI (31.8 [31.0; 32.6] versus 30.6 [30.5; 30.6] kg/m2, p = 0.004) and HbA1c (64.8 [62.1; 67.6] versus 59.0 [58.9; 59.1] mmol/mol, p < 0.0001). Insulin was used more frequently (62.3 [55.7; 68.5] versus 50.9 [50.7; 51.1] %, p = 0.001), only OAD/GLP-1 was similar, and nonpharmacological treatment was less common (13.3 [9.5; 18.3] versus 21.9 [21.7; 22.1] %, p = 0.002). Severe hypoglycemia (0.31 [0.238; 0.399] versus 0.06 [0.057; 0.060] events per patient-year, p < 0.0001), hypertension (86.1 [81.1; 90.0] versus 68.0 [67.8; 68.2] %, p < 0.0001), and thyroid disease (14.0 [10.1; 19.2] versus 4.6 [4.5; 4.7] %, p < 0.0001) were more prevalent. Depression occurred more often (10.5 [7.1; 15.2] versus 2.8 [2.7; 2.8] %, p < 0.0001). Conclusions. Clinical diabetes characteristics in psoriasis T2D patients were clearly worse compared to patients without psoriasis. Comorbid conditions and depression were more prevalent, and more intensive diabetes therapy was required.

High plasma sST2 levels in gastric cancer and their association with metastatic disease

BACKGROUND Gastric cancer (GC) is one of the most common and devastating tumor conditions. Its development is closely linked to an infection with Helicobacter pylori and chronic, cytokine-driven inflammation. The proinflammatory cytokine Interleukin-33 (IL-33), its membrane bound cellular receptor ST2L and its soluble receptor sST2 have recently been identified as important factors in various tumor conditions, but their role in GC remains ill-defined. METHODS Thirty patients with adenocarcinoma of the stomach or the esophagogastric junction were prospectively enrolled in the current study. 51 patients with Helicobacter pylori positive or negative gastritis and 40 healthy volunteers served as control group. Levels of IL-33 and sST2 were determined by ELISA and their relation to HP-status, tumor stage and survival was assessed. RESULTS Soluble ST2 levels in GC were significantly higher than in gastritis or healthy controls (p< 0.0001). Furthermore, higher levels of sST2 were seen in patients with lower degree of tumor differentiation. Soluble ST2 was significantly associated with a more advanced tumor stage (p= 0.018), metastatic disease (p= 0.014) and significantly correlated with the duration of the disease (p= 0.0017). Calculating the ratio of IL-33/sST2 allowed the discrimination of tumor and non-tumor patients. CONCLUSION Soluble ST2 is associated with advanced and metastatic disease in GC patients and significantly correlates with the duration of the disease. The IL-33/sST2 ratio may offer a new, interesting approach in identifying GC patients.

Defective IL-23/IL-17 Axis Protects p47phox−/− Mice from Colon Cancer

In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.

Cardivascular Risk Profile in Patients with Diabetes and Acromegaly or Cushing’s Disease – Analysis from the DPV Database

BACKGROUND Although diabetes is a common complication of acromegaly or Cushing´s disease, there are only few detailed studies with a focus on cardiovascular risk, metabolic control or diabetes therapy. Here, we provide a comprehensive characterization from the longitudinal DPV (Diabetes Patienten Verlaufsdokumentation) registry. METHODS Patients from the registry≥18 years of age with diabetes and acromegaly or Cushing´s disease were compared to patients with type 1 diabetes or type 2 diabetes using the statistical software SAS 9.4. RESULTS Patients with diabetes and acromegaly (n=52) or Cushings disease (n=15) were significantly younger at diabetes onset (median age 50.1 and 45.0 vs. 59.0 years in type 2 diabetes; both p<0.05). Dyslipidemia was common in both diseases (71.0% and 88.9% vs. 71.8% in type 2 diabetes; n.s.), while hypertension was most frequent in acromegaly (56.8% vs. 20.9% in type 1 diabetes, p<0.00001). 36.5% of patients with acromegaly and 46.7% with Cushing´s disease receive insulin, compared to 50.4% with type 2 diabetes. Oral antidiabetic drugs were used in 36.5% of patients with acromegaly and 40% with Cushing´s disease, with a predominance of biguanides and dipeptidyl peptidase-4 inhibitors. HbA1c was well controlled in both groups (median 7.0% and 6.5%; vs. 7.2% in type 2 diabetes). CONCLUSION Patients with acromegaly are at a high risk for cardiovascular disease, reflected by dyslipidemia and hypertension. A high proportion of patients with diabetes in acromegaly or Cushing´s disease receives insulin. Based on a multicenter register, a sufficient number of patients with rare forms of diabetes can be analyzed.

Neoadjuvant chemoradiation versus perioperative chemotherapy followed by surgery in resectable adenocarcinomas of the esophagogastric junction: A retrospective single center analysis

The current study presents a retrospective comparison, performed at a single academic center, of preoperative chemoradiation (CRT) and perioperative chemotherapy (CT) in addition to surgery in locally advanced but resectable adenocarcinoma of the esophagogastric junction (AEG). A total of 29 consecutive patients with locally advanced AEGs were retrospectively analyzed. Treatment consisted of preoperative CRT (mean dose, 45.0 Gy) plus two cycles of CT with cisplatin and 5-FU or perioperative CT with epirubicin, cisplatin and capecitabine (three cycles preoperatively and postoperatively). Within four to six weeks following preoperative treatment, surgical therapy was performed. Median overall survival was 21.0 months in the perioperative CT group versus 41.7 months in the CRT group [P=0.36; hazard ratio (HR), 1.50; 95% confidence interval (CI), 0.58–3.84]. Three-year survival rates were 55 and 38%, respectively, in favor of the CRT group, and progression-free survival was 20.0 months in the CT group compared with 24.1 months in the CRT group (P=0.71; HR, 1.19; 95% CI, 0.46–3.05). The total number of major surgical complications was almost equal in the two groups. Margin-free resections were achieved in all patients of the CRT group, but only 76.9% of the CT group (P=0.05). In addition, significantly higher R0 resection rates and an increased number of pathological complete remissions were demonstrated in the CRT group compared with those of the CT group. These results appear to indicate a trend for improved progression-free and overall survival for the CRT group. As postoperative morbidity and mortality rates were similar in the two groups, the results support the use of CRT for patients with advanced AEG tumors.

Adding Trastuzumab to Standard Chemotherapy in HER2-Positive Esophagogastric Adenocarcinoma: A Further Step Toward Personalized Medicine

aten Aberra, Philadelphia, PA uzhat A. Ahmad, Philadelphia, PA ans-Dieter Allescher, GermischPartenkirchen, Germany ordi Bruix, Barcelona, Spain in Chang, Los Angeles, CA illiam Chey, Ann Arbor, MI sutomu Chiba, Kyoto, Japan assimo Colombo, Milan, Italy Marcia Cruz-Corra, San Juan, PR Jason Dominitz, Seattle, WA James Farrell, Los Angeles, CA Lauren B. Gerson, Stanford, CA W. Ray Kim, Rochester, MN George Lau, Hong Kong, China Joseph M. Llovet, New York, NY Peter Mannon, Birmingham, AL Julian Panes, Barcelona, Spain Eamonn Quigley, Cork, Ireland Shiv K. Sarin, New Delhi, India Shamita B. Shah, Stanford, CA Nathan Subramaniam, Brisbane, Australia George Triadafilopoulos, Stanford, CA Kenneth K. Wang, Rochester, MN Thomas D. Wang, Ann Arbor, MI Alastair J. M. Watson, Liverpool, UK heila Crowe, Charlottesville, VA Raoul Poupon, Paris, France Stefan Zeuzem, Frankfurt, Germany