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Christ-Crain M.,University of Basel | Thomann R.,Buergerspital Solothurn | Zimmerli W.,Kantonsspital Liestal | Hoess C.,Kantonsspital Munsterlingen | Henzen C.,Kantonsspital Lucerne
Diabetologia | Year: 2014

Aims/hypothesis: Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in non-critical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in community-acquired pneumonia (CAP) patients. Methods: This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensive-care unit admission). Results: In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p < 0.05, ANOVA, all days). In diabetic patients (n = 156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels ≥ 9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p = 0.03). No effect modification by insulin treatment was detected (interaction terms p > 0.2 for all analyses). Conclusions/interpretation: Initial hyperglycaemia in non-diabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined. © 2013 Springer-Verlag Berlin Heidelberg.


Muzzarelli S.,University of Basel | Muzzarelli S.,University of California at San Francisco | Leibundgut G.,University of Basel | Leibundgut G.,University of California at San Diego | And 10 more authors.
American Heart Journal | Year: 2010

Background: Contemporary heart failure (HF) patients are elderly and have a high rate of early rehospitalization or death, resulting in a high burden for both the patients and the health care system. Prior studies were focused on younger and less well-characterized patients. We aimed to identify predictors of early hospital readmission and death in elderly patients with HF. Methods: Patients with chronic HF taking part in the TIME-CHF study (n = 614, age 77 ± 8 years, 41% female, left ventricular ejection fraction 35% ± 13%) were evaluated with respect to predictors of hospital readmission or death 30 and 90 days after inclusion. Demographic, clinical, laboratory, echocardiographic, and social variables were obtained at baseline and included in a multivariable logistic regression analysis to identify predictors of early events. Results: The rate of hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason for hospitalization was HF in 33%, other cardiovascular in 32%, and noncardiovascular in 45% of the cases, respectively. Predictors of readmission or death at 30 days were angina, lower systolic blood pressure, anemia, more extensive edema, higher creatinine levels, and dry cough; and at 90 days were coronary artery disease, prior pacemaker implantation, high jugular venous pressure, pulmonary rales, prior abdominal surgery, older age, and depressive symptoms. Conclusions: Early hospital readmission or death was frequent among elderly HF patients. A very large proportion of readmissions were due to noncardiovascular causes. In addition to clinical signs of HF, comorbidities are important predictors of early events in elderly HF patients. © 2010 Mosby, Inc.


Brunner-La Rocca H.-P.,University of Basel | Brunner-La Rocca H.-P.,Maastricht University | Rickenbacher P.,University Hospital Bruderholz | Muzzarelli S.,University of Basel | And 9 more authors.
European Heart Journal | Year: 2012

Aims Elderly heart failure (HF) patients are assumed to prefer improved quality of life over longevity, but sufficient data are lacking. Therefore, we assessed the willingness to trade survival time for quality-of-life (QoL) and the preferences for resuscitation.Methods and resultsAt baseline and after 12 and 18 months, 622 HF patients aged <60 years (77 ± 8 years, 74 NYHA-class


Gakis G.,University of Tübingen | Boorjian S.A.,Mayo Medical School | Briganti A.,Vita-Salute San Raffaele University | Joniau S.,Catholic University of Leuven | And 7 more authors.
European Urology | Year: 2014

Context Because pelvic lymph node (LN)-positive prostate cancer (PCa) is generally considered a regionally metastatic disease, surgery needs to be better defined. Objective To review the impact of radical prostatectomy (RP) and pelvic lymph node dissection (PLND), possibly in conjunction with a multimodal approach using local radiotherapy and/or androgen-deprivation therapy (ADT), in LN-positive PCa. Evidence acquisition A systematic Medline search for studies reporting on treatment regimens and outcomes in patients with LN-positive PCa undergoing RP between 1993 and 2012 was performed. Evidence synthesis RP can improve progression-free and overall survival in LN-positive PCa, although there is a lack of high-level evidence. Therefore, the former practice of aborting surgery in the presence of positive nodes might no longer be supported by current evidence, especially in those patients with a limited LN tumor burden. Current data demonstrate that the lymphatic spread takes an ascending pathway from the pelvis to the retroperitoneum, in which the internal and the common iliac nodes represent critical landmarks in the metastatic distribution. Sophisticated imaging technologies are still under investigation to improve the prediction of LN-positive PCa. Nonetheless, extended PLND including the common iliac arteries should be offered to intermediate- and high-risk patients to improve nodal staging with a possible benefit in prostate-specific antigen progression-free survival by removing significant metastatic load. Adjuvant ADT has the potential to improve overall survival after RP; the therapeutic role of a trimodal approach with adjuvant local radiotherapy awaits further elucidation. Age is a critical parameter for survival because cancer-specific mortality exceeds overall mortality in younger patients (<60 yr) with high-risk PCa and should be an impetus to treat as thoroughly as possible. Conclusions Increasing evidence suggests that RP and extended PLND improve survival in LN-positive PCa. Our understanding of surgery of the primary tumor in LN-positive PCa needs a conceptual change from a palliative option to the first step in a multimodal approach with a significant improvement of long-term survival and cure in selected patients. © 2013 European Association of Urology.


Kempf W.,Kempf und Pfaltz | Kazakov D.V.,Charles University | Schermesser M.,Dermatology Practice | Buechner S.A.,Histologische Diagnostik and Dermatology Practice | And 4 more authors.
Journal of Cutaneous Pathology | Year: 2012

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and has protean clinicopathological manifestations. Follicular or folliculotropic MF (FMF) is a rare variant, which histopathologically is characterized by pronounced folliculotropism of neoplastic T cells, with or without follicular mucinosis, and clinically by an impaired prognosis compared to classic MF. In contrast, unilesional MF is a very rare variant with an excellent prognosis, with a single case of large-cell transformation reported to date. The combination of folliculotropic and unilesional MF is very unusual, with only two cases reported to date. Here we report two patients with unilesional folliculotropic MF with progression to tumor stage in both patients. To the best of our knowledge, this is the first report on the disease evolution with large-cell transformation and progression of unilesional FMF. Complete remission was achieved by local radiation therapy in both patients. The differential diagnoses, classification and implications for the treatment of unilesional FMF as well as the pertinent literature are discussed. Copyright © 2012 John Wiley & Sons A/S.


Wijk S.S.-V.,Maastricht University | Maeder M.T.,Kantonsspital St Gallen | Nietlispach F.,University of Bern | Rickli H.,Kantonsspital St Gallen | And 6 more authors.
Circulation: Heart Failure | Year: 2014

Background.Therapy guided by N-terminal-pro-B-type natriuretic peptide (NT-proBNP) levels may improve outcomes in patients with chronic heart failure (HF), especially in younger patients with reduced left ventricular ejection fraction. It remains unclear whether treatment effects persist after discontinuation of the NT-proBNP.guided treatment strategy. Methods and Results.Trial of Intensified versus standard Medical therapy in Elderly patients with Congestive Heart Failure randomized 499 patients with HF aged .60 years with left ventricular ejection fraction .45% to intensified, NT- proBNP. guided versus standard, symptom-guided therapy into prespecified age groups (60.74 and .75 years) during 18 months. A total of 329 patients (92%) alive at 18 months agreed to long-term follow-up. HF medication was intensified to a larger extent in the NT-proBNP.guided group. During long-term, NT-proBNP.guided therapy did not improve hospital- free (primary end point: hazard ratio, 0.87; 95% confidence interval, 0.71.1.06; P=0.16) or overall survival (hazard ratio, 0.85; 95% confidence interval, 0.64.1.13; P=0.25) but did improve HF hospitalization-free survival (hazard ratio, 0.70; 95% confidence interval, 0.55.0.90; P=0.005). Patients aged 60 to 74 years had benefit from NT-proBNP.guided therapy on the primary end point and HF hospitalization-free survival, whereas patients aged .75 years did not (P<0.10 for interaction). In landmark analysis, there was no regression to the mean after cessation of the NT-proBNP.guided strategy. More intensified HF medication at month 12 was associated with better long-term HF hospitalization-free and overall survival. Conclusions.Intensified, NT-proBNP.guided therapy did not improve the primary end point compared with symptomguided therapy but did improve HF hospitalization-free survival. Within the subgroup of patients aged 60 to 74 years, it improved clinical outcome including the primary end point. These effects did not disappear after cessation of the NTproBNP. guided strategy on the long-term. This is possibly attributable to a more intensified HF medical therapy in the NT-proBNP.guided group. © 2013 American Heart Association, Inc.


Schoepfer A.M.,McMaster University | Schoepfer A.M.,University of Bern | Gonsalves N.,Northwestern University | Bussmann C.,Kantonsspital Lucerne | And 4 more authors.
American Journal of Gastroenterology | Year: 2010

OBJECTIVES: Esophageal dilation often leads to long-lasting relief of dysphagia in eosinophilic esophagitis (EoE). The aim of this study was to define the effectiveness, safety, and patient acceptance of esophageal dilation in EoE. In addition, we examined the influence of dilation on the underlying esophageal inflammation.METHODS: Two databases including 681 EoE patients were reviewed. Cohort 1 consisted of patients treated with dilation alone, whereas cohort 2 included patients treated with a combination of dilation and antieosinophilic medication. Patients from cohort 1 underwent a prospective histological reexamination and an evaluation using a questionnaire.RESULTS: In total, 207 EoE patients were treated with esophageal dilation, 63 in cohort 1 and 144 in cohort 2. Dilation led to a significant increase in esophageal diameter and to an improvement in dysphagia in both the cohorts (P0.001). After dilation, dysphagia recurred after 2322 months in cohort 1 and 2014 months in cohort 2. No esophageal perforation or major bleeding occurred. Among the patients surveyed, 74% reported retrosternal pain after dilation; however, all were agreeable to repeated dilation if required. Eosinophil peak infiltration, eosinophil load, and EoE-associated histological signs were not significantly affected by esophageal dilation.CONCLUSIONS: Esophageal dilation is highly effective in providing long-lasting symptom relief and can be performed safely with a high degree of patient acceptance. However, dilation is associated with postprocedural pain in most patients and does not influence the underlying inflammatory process. Symptom improvement despite persistence of inflammation suggests that tissue remodeling contributes substantially to symptom generation in EoE. © 2010 by the American College of Gastroenterology.


Sidler D.,University of Zürich | Winterhalder R.,Kantonsspital Lucerne | Huber G.,University of Zürich | Haerle S.K.,University of Zürich
Swiss Medical Weekly | Year: 2010

Background: Nasopharyngeal carcinoma is a rare tumor entity in Switzerland. In contrast, it is endemic in Asian and African countries. Retrospective studies have been conducted in order to identify risk factors and prognostic determinants of nasopharyngeal carcinoma. Nonetheless, these trials were mostly conducted in regions with high prevalence for the disease and little is known about the risk factors and prognosis of nasopharyngeal carcinoma for a non-endemic population in Western Europe. Methods: This retrospective trial was conducted to identify risk factors and prognostic determinants of nasopharyngeal carcinoma for a non-endemic population in Switzerland. Results: Overall survival was 91%, 77% and 58% for one, three and five years, respectively. Factors with favourable prognostic value were concomitant radiochemotherapy regimens, photon radiotherapy, and a delay between diagnosis and first therapy session of less than ten weeks, respectively. Factors with unfavourable prognostic values were age over 65 years at time of diagnosis and nasopharyngeal carcinoma of WHO type I. Conclusion: Risk factors, biological behaviour and survival are well comparable between endemic and non-endemic populations for nasopharyngeal carcinoma. Nonetheless, an aggressive diagnostic procedure and sophisticated interdisciplinary therapy are indispensable in order to achieve favourable outcome. Therefore, diagnosis and therapy of nasopharyngeal carcinoma in non-endemic populations should be limited to highly specialized tertiary centres.


Zueger T.,University of Bern | Kirchner P.,University of Bern | Herren C.,University of Bern | Fischli S.,Kantonsspital Lucerne | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA). Objective: Our objective was to assess whether higher glucocorticoid replacement doses are associated with increased mortality in patients with NFPA and HPA axis insufficiency. Design, Participants, and Intervention: Weincluded 105 patients receiving glucocorticoid replacement after pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients were grouped according weight-adapted and absolute hydrocortisone (HC) replacement doses. Mortality was assessed using Kaplan-Meier methodology as well as multivariable Cox regression models. Setting: This was a retrospective analysis conducted at a tertiary referral center. Main Outcome: We evaluated overall mortality based on HC replacement doses. Results: Average age at inclusion was 58.9 ± 14.8 yr, and mean follow-up was 12.7 ± 9.4 yr. The groups did not differ according to age, follow-up time, pattern of hypopituitarism, and comorbidities. Kaplan-Meier survival probabilities differed significantly when comparing individuals with differing weight-adjusted HC dose (P = 0.001) as well as absolute HC dose (5-19, 20-29, and ≥30 mg, P = 0.009). Hazard ratios for mortality increased from 1 (0.05-0.24 mg/kg) to 2.62 (0.25- 0.34 mg/kg) to 4.56 (≥0.35 mg/kg, P for trend = 0.006) and from 1 (5-19 mg) to 2.03 (20-29 mg) to 4 (≥30 mg, P for trend = 0.029), respectively. Conclusion: Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients. Copyright © 2012 by The Endocrine Society Printed in U.S.A.


Dilger K.,Dr. Falk Pharma GmbH | Lopez-Lazaro L.,Covance | Marx C.,Covance | Bussmann C.,Kantonsspital Lucerne | Straumann A.,Swiss EoE Clinic
Digestion | Year: 2013

Background/Aims: Topically administered glucocorticoids such as budesonide have the potential of being established as first-line medical treatment of eosinophilic esophagitis (EoE). Safety of budesonide is based on high elimination by cytochrome P450 3A (CYP3A) enzymes. We aimed to investigate systemic absorption and elimination of a new budesonide formulation in patients with active EoE in comparison with healthy controls. Methods: After single and multiple doses of orodispersible budesonide (4 mg/day) the parent drug, its CYP3A-dependent metabolites, and endogenous cortisol were determined in 12 adult patients with active EoE and 12 healthy controls. An approved ileal-release formulation of budesonide was taken for reference. Molar ratios of metabolite formation in plasma were used as indices of CYP3A metabolic function. Results: CYP3A-dependent metabolite formation was significantly reduced in patients with active EoE as compared to healthy controls. Impaired biotransformation was reflected by a significantly higher extent of budesonide absorption and elongated elimination half-life in EoE patients. Comparison of morning serum cortisol levels at baseline with those after 1 week of treatment with budesonide revealed a significant decrease in EoE patients but not in healthy subjects. Conclusion: Active EoE is associated with reduced elimination of budesonide via CYP3A, the major subfamily of drug-metabolizing enzymes in humans. Copyright © 2013 S. Karger AG, Basel.

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