Augsburg, Germany
Augsburg, Germany

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Pletz M.W.,Jena University Hospital | Pletz M.W.,CAPNETZ Foundation | Terkamp C.,Hannover Medical School | Schumacher U.,Jena University Hospital | And 51 more authors.
Respiratory Research | Year: 2014

Objectives: We aimed to explore the association between vitamin D levels and the severity, mortality and microbiological etiology of community-acquired pneumonia.Methods: Vitamin D levels (both, the reservoir form 25-OH and the activated form 1,25-OH2) of 300 randomly selected patients with community-acquired pneumonia due to pre-specified pathogens included in the German competence network (CAPNETZ) study were measured. Prior to statistical analysis, values of 25-OH and 1,25-OH2 were power-transformed to achieve parametric distribution. All further analyses were performed with seasonally and age adjusted values.Results: There was only a modest (Spearman Coefficient 0.38) positive correlation between 25-OH and 1,25-OH2. For 1,25-OH2 but not 25-OH, the general linear model revealed a significant inverse correlation between serum concentration and CURB score (p = 0.011). Liver and respiratory co-morbidity were associated with significantly lower 25-OH values and renal co-morbidity with significantly lower 1,25-OH2 values. No significant differences of 1,25-OH2 or 25-OH between different pathogens (influenza virus, Legionella spp., Streptococcus pneumoniae) were detected.Conclusion: For 1,25-OH2, we found a significant and independent (controlled for age, season and pathogen) negative correlation to pneumonia severity. Therefore, supplementation of non-activated vitamin D to protect from pneumonia may be non-sufficient in patients that have a decreased capacity to hydroxylate 25-OH to 1,25-OH2. © 2014 Pletz et al.; licensee BioMed Central Ltd.


Majcher-Peszynska J.,University of Rostock | Loebermann M.,University of Rostock | Klammt S.,University of Rostock | Frimmel S.,University of Rostock | And 50 more authors.
Infection | Year: 2014

Purpose: Age-related physiological changes affect body systems, altering pharmacokinetics, which may potentiate or alter the effects of drugs. The aim of this study was to assess the influence of age on the steady-state pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam in the population of elderly patients (age ≥65 years) with community-acquired pneumonia (CAP). Patients and methods: The pharmacokinetics and pharmacokinetic/pharmacodynamic parameters of ampicillin/sulbactam were determined at steady state in a total of 13 elderly patients with CAP following the administration of multiple intravenous doses of 2 g ampicillin + 1 g sulbactam (Unacid®, Pfizer), each over 15 min thrice a day. Results A reduced Cmax, AUC0-8 h and total clearance, a prolonged half-life, and an increased steady-state volume of distribution were observed for ampicillin. The mean estimated free Cmin of 1.8 mg/L for ampicillin was higher than that predicted to be effective against Streptococcus pneumoniae. Based on an MIC90 of 1 mg/L for Streptococcus pneumoniae, the calculated T > MIC and T > 4 x MIC for ampicillin was 75-100% (median 100%) and 12.5-100% (median 50%), respectively. A T > 4 x MIC of at least 50% was achieved in 7 of 13 elderly patients with CAP. Conclusions: Age and, probably, pneumonia did affect the pharmacokinetics of ampicillin and sulbactam. Despite the reduced Cmax, adequate free Cmin/MIC90 ratios due to impaired renal function were observed in elderly patients with CAP. In elderly patients without renal impairment and/or in severe infection with less susceptible pathogens, more frequent dosing of ampicillin 2 g/sulbactam 1 g can be necessary to avoid the risk of underdosing in CAP. © Springer-Verlag 2013.


Dumke R.,TU Dresden | Schnee C.,Friedrich Loeffer Institute | Pletz M.W.,Jena University Hospital Center for Infectious Diseases and Infection Control | Rupp J.,CAPNETZ STIFTUNG | And 45 more authors.
Emerging Infectious Diseases | Year: 2015

Mycoplasma pneumoniae and Chlamydia spp., which are associated with community-acquired pneumonia (CAP), are diffcult to propagate, and can cause clinically indistinguish able disease patterns. During 2011-2012, we used molecu lar methods to test adult patients in Germany with confrmed CAP for infection with these 2 pathogens. Overall, 12.3% (96/783) of samples were positive for M. pneumoniae and 3.9% (31/794) were positive for Chlamydia spp.; C. psittaci (2.1%) was detected more frequently than C. pneumoniae (1.4%). M. pneumoniae P1 type 1 predominated, and lev els of macrolide resistance were low (3.1%). Quarterly rates of M. pneumoniae-positive samples ranged from 1.5% to 27.3%, showing a strong epidemic peakforthese infections, but of Chlamydia spp. detection was consistent throughout the year. M. pneumoniae-positive patients were younger and more frequently female, had fewer co-occurring condi tions, and experienced milder disease than did patients who tested negative. Clinicians should be aware of the epidemi- ology of these pathogens in CAP. © 2015, Centers for Disease Control and Prevention (CDC). All rights reserved.


Klapdor B.,Thoraxzentrum Ruhrgebiet | Ewig S.,Thoraxzentrum Ruhrgebiet | Schaberg T.,Diakoniekrankenhaus | Rohde G.,Maastricht University | And 42 more authors.
Journal of Infection | Year: 2012

Objective: Nursing home-acquired pneumonia characteristically affects elderly patients with multiple comorbidities; it is associated with multidrug-resistant (MDR) pathogens and a high mortality. We studied the specific impact of age on the presentation, etiology and outcome of patients with NHAP. Methods: Data from the prospective multicenter CAPNETZ database were used for a comparison of the hospitalized younger nursing home residents with pneumonia to those aged ≥ 65 years as regards clinical presentation, comorbidity, severity at presentation, etiology, and outcome. Results: Amongst 618 patients with NHAP, 16% of patients (n = 100) were aged; 65 years. Comorbidity was present in most patients with NHAP but the pattern of comorbidity differed significantly. The rate of potential MDR pathogens was low among both age groups (together around 5%). According to the CRB-65 score, NHAP presentation was less severe in the younger patients. Short- and long-term mortality was twice as low in the younger patients with rates of 12.9% vs 26.6%, and 24.3% vs 43.8%, p = 0.014 and 0.002), respectively. In contrast, the usage of mechanical ventilation was more than two-fold higher (12% vs 5%) (p = 0.008) in younger patients. Antimicrobial treatment strategies did not account for different outcomes. Conclusions: A considerable proportion of patients with NHAP are: 65 years of age. They differ from older patients in terms of clinical presentation, frequency and type of comorbidity, as well as outcome. NHAP is a heterogeneous entity, with age and comorbidity as the main determinant of NHAP characteristics. © 2012 The British Infection Association.


Cacchi C.,Institute of Pathology | Cacchi C.,Institute For Pathologie | Arnholdt H.M.,Institute of Pathology | Jahnig H.,Institute of Pathology | And 4 more authors.
International Journal of Colorectal Disease | Year: 2012

Purpose The purpose of the present study is to characterise the lymphatic vessel density (LVD) in the T3 colorectal carcinoma and to correlate it with N status, grading and presence of tumour budding. Methods A total of 56 cases of T3 colorectal carcinoma were retrieved from the pathology's archive of Klinikum Augsburg. All slides were stained immunohistochemically with D2-40 (lymphatic endothelium) and with pancytokeratin to assess the tumour budding. Tumour budding and lymph vessel density were investigated independently by BM and CC. The highest density of lymphatic vessels was counted both in tumour centre (ILVD) and at the periphery of the tumour (PLVD) within an area of 0.24 mm2. Results Due to the strong intra-observer (BM and CC) difference in ILVD and PLVD, all cases were re-evaluated establishing a consensus that has been used for the further analyses. There was a significant difference between PLVD and ILVD (12±4 versus 6±3; P<0.001). Moreover, we found a non-significant trend towards high PLVD in the cases with nodal metastasis versus the negative one, 13±5/ hpf versus 11±4 (P=0.072). There was no association between tumour budding and ILVD and PLVD (P=0.249 and 0.38). Conclusion Colorectal carcinoma induces lymphangiogenesis. A higher PLVD could increase the capability of cancer cell to invade the lymphatic system. However, the obvious difficulties in immunohistochemical evaluation and the rather small differences between nodal positive and negative cases in T3 colorectal cancer seem to limit the clinical value of LVD evaluation. © Association of Clinical Biochemists of India 2012.


Cannavo S.,Messina University | Bogazzi F.,Ospedale Cisanello | Colao A.,University of Naples Federico II | De Marinis L.,Catholic University of the Sacred Heart | And 5 more authors.
Journal of Endocrinological Investigation | Year: 2015

Objective: GH receptor antagonist pegvisomant is indicated for treatment of patients with resistant acromegaly. We compared safety and treatment outcomes of pegvisomant therapy in patients managed by Italian centers enrolling less or more than 15 cases in ACROSTUDY, a safety surveillance study of long-term pegvisomant treatment of patients with acromegaly. A noninterventional safety surveillance study in which safety and treatment outcomes of pegvisomant were evaluated on the basis of data collected during a 7-year period. Methods: A total of 204 acromegaly patients treated by seven centers enrolling 16-49 patients each (group A) and 137 subjects by 18 centers following 3-14 cases (group B). Results: Patients of group A and B were treated for 4.4 ± 2.7 and 4.2 ± 2.2 years, respectively. IGF-1 ULN normalized in 64.4 % (n = 56) and 54.4 % (n = 31) in group A and B, respectively, after 1-year treatment, and in 57.3 % (n = 106) and 72.5 % (n = 87) at last visit. Starting doses were significantly higher in group A. They were progressively increased during treatment in both groups, but were higher in uncontrolled patients than in controlled ones only in group A. Reported adverse events were more frequent, and the prevalence of patients with adverse events was higher in group B. Conclusions: On the basis of this original study approach, we could speculate that in the centers in which more patients are treated with pegvisomant, less adverse events are reported, but the long-term effectiveness is lower than in centers with less cases, perhaps because of an inadequate patient's selection. © 2015 Italian Society of Endocrinology (SIE).


PubMed | Pfizer, University of Naples Federico II, University of Turin, Catholic University of the Sacred Heart and 3 more.
Type: Journal Article | Journal: Journal of endocrinological investigation | Year: 2015

GH receptor antagonist pegvisomant is indicated for treatment of patients with resistant acromegaly. We compared safety and treatment outcomes of pegvisomant therapy in patients managed by Italian centers enrolling less or more than 15 cases in ACROSTUDY, a safety surveillance study of long-term pegvisomant treatment of patients with acromegaly. A noninterventional safety surveillance study in which safety and treatment outcomes of pegvisomant were evaluated on the basis of data collected during a 7-year period.A total of 204 acromegaly patients treated by seven centers enrolling 16-49 patients each (group A) and 137 subjects by 18 centers following 3-14 cases ( group B).Patients of group A and B were treated for 4.42.7 and 4.22.2years, respectively. IGF-1 ULN normalized in 64.4% (n=56) and 54.4% (n=31) in group A and B, respectively, after 1-year treatment, and in 57.3% (n=106) and 72.5% (n=87) at last visit. Starting doses were significantly higher in group A. They were progressively increased during treatment in both groups, but were higher in uncontrolled patients than in controlled ones only in group A. Reported adverse events were more frequent, and the prevalence of patients with adverse events was higher in group B.On the basis of this original study approach, we could speculate that in the centers in which more patients are treated with pegvisomant, less adverse events are reported, but the long-term effectiveness is lower than in centers with less cases, perhaps because of an inadequate patients selection.


Lichtmannegger I.,Institute of Pathology | Golder S.,III. Medical Clinic | Probst A.,III. Medical Clinic | Donmez G.,III. Medical Clinic | And 6 more authors.
Virchows Archiv | Year: 2014

Fibroelastotic changes (FEC) and especially elastotic polyps of the gastrointestinal (GI) tract are considered rare benign lesions. They consist of accumulations of elastic fibers within the mucosal, submucosal, or muscular layer, occurring in all parts of the GI tract and often appearing as polyps, but also as diffuse non-polyp-forming deposits. They have been the subject of only a few studies. To explore the clinical and histopathological features of FEC in the GI tract, a series of 162 elastotic lesions was collected within a 2-year period. The clinical data and endoscopic findings were correlated. FEC appeared as polyp-forming lesions of the large intestine in 23 samples (14 %), all other samples concerning histological findings without an identifiable gross mass. Frequently related findings were postinterventional status (9 %), previous irradiation (7 %), and history of GI lymphoma (4 %). Eight samples (5 %) presented endoscopically with lesions justifying surgical intervention. We identified three different histological patterns of FEC, which we have called fibroelastosis, angioelastosis, and elastofibroma. Consistent with previous studies, CD34 immunohistochemical staining (performed on 38 polypoid FEC specimens) showed an increase of CD34-positive mesenchymal cells in 95 % of immunostained samples, suggesting a potential role for CD34-positive mesenchymal cells in the accumulation of elastic fibers. In conclusion, FEC are more common in the GI tract than previously recognized. They often present as a benign polyp. Many accompany other diseases like ulcers and atrophic gastritis or represent a residual finding after an intervention. © 2014, Springer-Verlag Berlin Heidelberg.


Thomaidis T.,Johannes Gutenberg University Mainz | Weinmann A.,Johannes Gutenberg University Mainz | Sprinzl M.,Johannes Gutenberg University Mainz | Kanzler S.,Leopoldina Hospital | And 7 more authors.
International Journal of Clinical Oncology | Year: 2014

Background: The impact of erythropoiesis-stimulating agents in chemotherapy-induced anemia has been a constant topic of debate over recent years. We prospectively assessed the efficacy of epoetin beta (Epo-b) in improving hemoglobin (Hb) levels and outcome in patients within an open label, randomized clinical phase II trial with advanced or metastatic gastric/esophagogastric cancer. Methods: Previously untreated patients were randomized to receive 3-weekly cycles of capecitabine (1000 mg/m2 bid) for 14 days plus on day 1 either irinotecan 250 mg/m2 or cisplatin 80 mg/m2. Epo-b (30000 IU once weekly) was initiated in patients with Hb <11 g/dl and continued until Hb ≥12 g/dl was reached. If after 4 weeks the Hb increase was <0.5 g/dl, Epo-b was increased to 30000 IU, twice weekly. Results: Of 118 patients enrolled, 32 received Epo-b treatment; of these, 65 % achieved an increase in Hb levels of at least 2 g/dl, with 74 % achieving the target Hb of ≥12 g/dl. Within the study population, patients receiving Epo-b showed better overall survival (median 14.5 vs. 8.0 months, P = 0.056) as well as a significantly improved disease control rate (78 vs. 55 %, P = 0.025). Patients in the irinotecan group profited significantly (P < 0.05) in terms of progression-free survival and overall survival under Epo-b treatment (median 6.5 vs 4.1 months and median 15.4 vs 8.4 months, respectively). Conclusions: Epo-b was effective in raising Hb levels in patients with advanced esophagogastric cancer. Patients receiving Epo-b had a significantly increased response to chemotherapy and a clear trend to improved survival. © 2013 Japan Society of Clinical Oncology.


Markl B.,Institute of Pathology | Herbst C.,Institute of Pathology | Cacchi C.,Institute of Pathology | Schaller T.,Institute of Pathology | And 4 more authors.
International Journal of Colorectal Disease | Year: 2013

Purpose: Minimal lymph node involvement is a potential prognostic factor in colorectal cancer. The International Union Against Cancer defined tumour deposits between 0.2 and 2 mm as micrometastases and clusters and single-cell infiltrations below this cutoff as isolated tumour cells. Nevertheless, only a minority of studies discriminated metastatic involvements according to this definition. Methods: In order to investigate the prognostic significance of micrometastases (0.2-2 mm), we performed a retrospective study enrolling 44 routinely diagnosed micrometastatic cases within 15 years which represent about 1 % of our cases. These cases have been re-evaluated. Results: Seven of the micrometastatic cases turned out to be macrometastases after step sectioning. Complete follow-up was available in 33 remaining cases. Collections of node-negative and macrometastatic cases served as control groups. The Kaplan-Meier curves of macro- and micrometastatic cases showed a similar adverse course (p = 0.830) especially during the first 40 months. The 5-year-survival rates were 51, 60 and 64 months for macro-, micrometastatic and node-negative cases, respectively. The difference in overall survival, however, reached only a statistical trend and was not significant (p = 0.137). After re-evaluation with step sections and cytokeratin immunohistochemistry out of an initial 91 node-negative cases, 11 (12 %) cases were identified with isolated tumour cells and one (1 %) case with a micrometastasis. Conclusions: Our data show that micro- and macrometastatic colorectal cancers show very similar survival rates. Therefore, efforts to improve the detection of lymph node micrometastases seem to be justified. © 2013 Springer-Verlag Berlin Heidelberg.

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