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Lugano, Switzerland

Denti M.,Istituto Clinico Humanitas | Arrigoni P.,University of Milan | Volpi P.,Istituto Clinico Humanitas | Bait C.,Istituto Clinico Humanitas | And 2 more authors.
Orthopedics | Year: 2014

The anteroposterior (AP) stability of standard anterior cruciate ligament (ACL) reconstruction, referred to as "vertical," was compared with that of a modified femoral position, referred to as "horizontal," which is lower than and anterior to an operative knee at 90° flexion. Two consecutive series of 50 patients underwent vertical and horizontal arthroscopic single-bundle ACL reconstruction, respectively. For vertical reconstruction, the clock position was chosen, placing the graft at 10:30 in right knees and 1:30 in left knees, 1 to 2 mm anterior to the posterior femoral cortical cortex and at the back of the resident ridge. In the horizontal reconstruction, the transplant replaced the original ligament insertion at approximately the 9:30 o'clock position in right knees and the 2:30 o'clock position in left knees, approximately 2 mm in front of the posterior femoral cortical cortex. One year after surgery, the results of stabilometric evaluation revealed good performance after horizontal transplant. The mean clinical results changed from 1.0 (±1.3) mm for vertical to 0.7 (±1.3) mm for horizontal reconstruction. Source


Sahnane N.,University of Insubria | Frattini M.,Institute of Pathology | Bernasconi B.,University of Insubria | Zappa F.,Clinica Luganese | And 8 more authors.
Clinical Lung Cancer | Year: 2016

Introduction In lung adenocarcinoma (ADC), anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements are mutually exclusive with epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. However, the existence of double-positive (DP) patients have been sporadically described. We identified DP cases in therapy-naive ALK-rearranged ADC and characterized the biology of these tumors to better understand the clinical response to tyrosine kinase inhibitors (TKIs). Materials and Methods We selected 42 ALK-positive ADCs from a multicentric series of 301 cases of ADCs. A mutational analysis was performed using Sanger and/or pyrosequencing to address exons 18-21 of EGFR and codons 12-13 of the KRAS gene. In addition, the KRAS and EGFR copy number was investigated using fluorescent in situ hybridization. DP patients were treated with TKIs, and their response was evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. Results Eight of 42 ALK-positive ADCs (19%) demonstrated a concomitant mutation in the EGFR (3 cases) or KRAS (5 cases) genes and were classified as DP. All DP cases displayed copy number gains in the EGFR or KRAS gene because of polysomy or gene amplification. In the latter cases, a mutant allele-specific imbalance was observed. Four patients were treated with TKIs. The 2 EGFR-mutant DP patients demonstrated a better response to crizotinib compared with erlotinib. The 2 KRAS-mutant DP patients experienced opposite responses to crizotinib. Conclusion The incidence of DP ADC is not negligible. Patients with ALK/EGFR might benefit more from crizotinib compared with erlotinib administration, although the efficacy of TKIs in patients with ALK/KRAS remains unclear. An integrated targeted therapy should be considered for patients with DP ADC. © 2016 Elsevier Inc. All rights reserved. Source


Kachlik D.,Charles University | Musil V.,Charles University | Vasko S.,Charles University | Klaue K.,Clinica Luganese | And 2 more authors.
Acta Chirurgica Belgica | Year: 2010

Diseases and injuries of several specific structures in the heel region have been an enduring focus of medicine. The anatomical terminology of many of mese structures has not been established until recently. The aim of the study was a historical analysis of the advances of anatomical terminology of three selected morphological units in the heel region - the Achilles tendon, calcaneus and retrocalcaneal bursa. It starts with a critical evaluation of the mythological eposes, the Illiad and Odyssey, describing the exploits of heroes in the Trojan war, followed by a review of relevant terms used for me designation of selected heel structures in the Middle Ages as well as in the 18th and 19th centuries. Principal versions of Latin anatomical terms used for me denotation of the mentioned structures are discussed. Recently applicable Latin terms and their recommended English synonyms, according to me latest version of Terminologia Anatómica (1998) are summed up. It surveys examples of .,very appropriate' terms, which are frequently used in clinical literature. The authors consider the use of official anatomical terms (both Latin and English) as an important step for the improvement of the clinical expressions and formulations. Source


Joerger M.,Cantonal Hospital | Baty F.,Cantonal Hospital | Fruh M.,Cantonal Hospital | Droege C.,University of Basel | And 11 more authors.
Lung Cancer | Year: 2014

Objectives: Molecular subclassification of non small-cell lung cancer (NSCLC) is essential to improve clinical outcome. This study assessed the prognostic and predictive value of circulating micro-RNA (miRNA) in patients with non-squamous NSCLC enrolled in the phase II SAKK (Swiss Group for Clinical Cancer Research) trial 19/05, receiving uniform treatment with first-line bevacizumab and erlotinib followed by platinum-based chemotherapy at progression. Materials and methods: Fifty patients with baseline and 24. h blood samples were included from SAKK 19/05. The primary study endpoint was to identify prognostic (overall survival, OS) miRNA's. Patient samples were analyzed with Agilent human miRNA 8x60K microarrays, each glass slide formatted with eight high-definition 60K arrays. Each array contained 40 probes targeting each of the 1347 miRNA. Data preprocessing included quantile normalization using robust multi-array average (RMA) algorithm. Prognostic and predictive miRNA expression profiles were identified by Spearman's rank correlation test (percentage tumor shrinkage) or log-rank testing (for time-to-event endpoints). Results: Data preprocessing kept 49 patients and 424 miRNA for further analysis. Ten miRNA's were significantly associated with OS, with hsa-miR-29a being the strongest prognostic marker (HR = 6.44, 95%-CI 2.39-17.33). Patients with high has-miR-29a expression had a significantly lower survival at 10 months compared to patients with a low expression (54% versus 83%). Six out of the 10 miRNA's (hsa-miRN-29a, hsa-miR-542-5p, hsa-miR-502-3p, hsa-miR-376a, hsa-miR-500a, hsa-miR-424) were insensitive to perturbations according to jackknife cross-validation on their HR for OS. The respective principal component analysis (PCA) defined a meta-miRNA signature including the same 6 miRNA's, resulting in a HR of 0.66 (95%-CI 0.53-0.82). Conclusion: Cell-free circulating miRNA-profiling successfully identified a highly prognostic 6-gene signature in patients with advanced non-squamous NSCLC. Circulating miRNA profiling should further be validated in external cohorts for the selection and monitoring of systemic treatment in patients with advanced NSCLC. © 2014 Elsevier Ireland Ltd. Source


Gonzalez A.,University of Basel | Schmitter K.,University of Basel | Hirsch H.H.,University of Basel | Garzoni C.,Clinica Luganese | And 9 more authors.
Genes and Immunity | Year: 2014

Previous studies have associated activating Killer cell Immunoglobulin-like Receptor (KIR) genes with protection from cytomegalovirus (CMV) replication after organ transplantation. Whether KIR-associated protection is operating in the context of primary infection, re-activation, or both, remains unknown. Here we correlated KIR genotype and CMV serostatus at the time of transplantation with rates of CMV viremia in 517 heart (n=57), kidney (n=223), liver (n=165) or lung (n=72) allograft recipients reported to the Swiss Transplant Cohort Study. Across the entire cohort we found B haplotypes-which in contrast to A haplotypes may contain multiple activating KIR genes-to be protective in the most immunosuppressed patients (receiving anti-thymocyte globulin induction and intensive maintenance immunosuppression) (hazard ratio after adjustment for covariates 0.46, 95% confidence interval 0.29-0.75, P=0.002). Notably, a significant protection was detected only in recipients who were CMV-seropositive at the time of transplantation (HR 0.45, 95% CI 0.26-0.77, P=0.004), but not in CMV seronegative recipients (HR 0.59, 95% CI 0.22-1.53, P=0.28). These data indicate a prominent role for KIR-and presumably natural killer (NK) cells-in the control of CMV replication in CMV seropositive organ transplant recipients treated with intense immunosuppression. © 2014 Macmillan Publishers Limited All rights reserved. Source

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