On the rationale of population screening for chronic kidney disease : a public health perspective

Chronic kidney disease (CKD) and its complications represent an enormous and increasing public health burden worldwide [1]. More than one in ten adults suffers from CKD in the general population [2], with a majority of people being in its early stages (i.e. 1 to 3) [2]. In the general population, the prevalence of CKD sharply increases with age [3]. CKD can be considered as a condition associated with premature ageing with accelerated vascular disease [4]. The large number of people with CKD, or at high risk of CKD (i.e. patients with hypertension, diabetes and/or CVD), implies that primary care providers and specialists other than nephrologists frequently encounter patients with CKD [5], a situation in which most CKD cases are diagnosed via opportunistic kidney function screening or automated eGFR reporting. The aim of this review is to discuss the rationale and currently available evidence for, or against, population-based screening for CKD. The focus will be on the situation of screening asymptomatic individuals at early stages of CKD regardless of the presence or absence of CKD risk factors.

Clinical utility of a molecular test in adjuvant treatment decision making in women with endocrine-sensitive early stage breast cancer: a retrospective, single center one year experience

Background. Molecular tests for breast cancer (BC) risk assessment are reimbursed by health insurances in Switzerland since the beginning of year 2015. The main current role of these tests is to help oncologists to decide about the usefulness of adjuvant chemotherapy in patients with early stage endocrine-sensitive and human epidermal growth factor receptor 2 (HER2)-negative BC. These gene expression signatures aim at predicting the risk of recurrence in this subgroup. One of them (OncotypeDx/OT) also predicts distant metastases rate with or without the addition of cytotoxic chemotherapy to endocrine therapy. The clinical utility of these tests -in addition to existing so-called "clinico-pathological" prognostic and predictive criteria (e.g. stage, grade, biomarkers status)-is still debated. We report a single center one year experience of the use of one molecular test (OT) in clinical decision making. Methods. We extracted from the CHUV Breast Cancer Center data base the total number of BC cases with estrogen-receptor positive (ER+), HER2-negative early breast cancer (node negative (pN0) disease or micrometastases in up to 3 lymph nodes) operated between September 2014 and August 2015. For the cases from this group in which a molecular test had been decided by the tumor board, we collected the clinicopathologic parameters, the initial tumor board decision, and the final adjuvant systemic therapy decision. Results. A molecular test (OT) was done in 12.2% of patients with ER + HER2 negative early BC. The median age was 57.4 years and the median invasive tumor size was 1.7 cm. These patients were classified by ODX testing (Recurrence Score) into low-, intermediate-, and high risk groups, respectively in 27.2%, 63.6% and 9% of cases. Treatment recommendations changed in 18.2%, predominantly from chemotherapyendocrine therapy to endocrine treatment alone. Of 8 patients originally recommended chemotherapy, 25% were recommended endocrine treatment alone after receiving the Recurrence Score result. Conclusions. Though reimbursed by health insurances since January 2015, molecular tests are used moderately in our institution as per the decision of the multidisciplinary tumor board. It's mainly used to obtain a complementary confirmation supporting the decision of no chemotherapy. The OncotypeDx Recurrence Score results were in the intermediate group in 66% of the 9 tested cases but contributed to avoid chemotherapy in 2 patients during the last 12 months.

Perivascular epithelioid cell tumor (PEComa) of the uterus: A case report

Background. Perivascular epithelioid cell tumors (PEComas) are a rare family of mesenchymal tumors arising in a wide array of anatomic locations and characterized by coexpression of melanocytic and muscle markers. The uterus accounts for around one-fourth of the overall PEComa cases reported in the literature. Methods. We report a case of PEComa of the uterus with multiple malignancy features. Results. A uterine mass suspect for leiomyosarcoma was found in a 53-year-old woman with post-menopausal bleeding. Total hysterectomy and bilateral adnexectomy was performed. The tumor measured 7 cm in diameter, was unique, well-circumscribed, nodular, and whiteyellow without haemorrhage or necrosis. Microscopically, two populations of cells could be seen: small fusiform cells growing in fascicles resembling a smooth muscle tumor, and large epithelioid cells with abundant pale vacuolated cytoplasm growing in a diffuse pattern. Cytologic atypias were marked and mitoses numerous and often atypical in the second component. The tumor infiltrated into the myometrium with lymphovascular invasion. Immunostains showed positivity for MelanA, HMB45, smooth muscle actin, CD10, TFE3 and cathepsin K. Conclusions. This PEComa case presents several of the recently precised criteria for malignancy (Schoolmeester JK et al. Perivascular epithelioid cell neoplasm (PEComa) of the gynecologic tract: Clinicopathologic and immunohistochemical characterization of 16 cases. Am J Surg Pathol 2014; 38:176-188).

Non-small cell lung cancer: the prevalence of oncogenic driver mutations in Switzerland

Background. Predictive molecular marker analyses are standard of care in order to select non-small cell lung cancer (NSCLC) patients for targeted therapies. The aim of this study was to determine the prevalence of targetable oncogenic driver mutations including EGFR, KRAS, BRAF, HER2, ALK and ROS1 in Switzerland. Methods. Eight Swiss pathology institutions provided retrospective and anonymized data on their predictive molecular marker results performed on NSCLC from January 2012 to December 2014. Clinico-pathological data were recorded including age, gender, histological NSCLC-subtype and specimen type (biopsy, conventional cytology and cell block, respectively) used for molecular analyses. The prevalence of oncogenic mutations were calculated and compared between the centres. Results. A total of 4187 NSCLC were included into the study. The median age was 67 years and 55% were male patients. The tumor specimens for molecular analysis were mostly derived from biopsies (69%), 26% were from conventional cytology specimens and only in 5% from cell blocks. The most prevalent gene mutation was KRAS with 30.6% (range: 27.3-33.9%), followed by EGFR, BRAF and HER2 mutations in 12.2% (range: 10.2-13.1%), 3.9% (range: 2.5-5.6%) and 1.1% (range: 0.9-4.0%), respectively, without significant differences between the eight centers. Concomitant EGFR and KRAS mutations were detected in only 3/2027 NSCLC. In contrast the prevalence of ALK (mean 6.5%, range: 2.8-11.7%) and ROS1 (mean 2.4%, range: 1.5-6.2%) rearrangements varied significantly between centers. Conclusions. The Prevalence of EGFR, KRAS, BRAF and HER2 mutations are well in line with data from other West European populations. Concomitant EGFR, KRAS, BRAF or HER2 mutations are exceptional. ALK FISH results vary significantly between the eight centres. Concomitant ALK FISH positive results in NSCLC harbouring other oncogenic driver mutation have only been observed in two smaller centres, highlighting the difficulty in ALK-FISH interpretation.

Cerebriforms cells in cerebrum: an unusual finding

Background. Mycosis Fungoides (MF) is the most common cutaneous T-cell lymphoma, and large cell trasformation (tMF) is an adverse prognostic event. Extra-cutaneous dissemination can occur in the course of the disease, but dissemination to the central nervous system (CNS) is uncommon. Moreover, CNS lymphomas are overall rare and most often of B-cell phenotype. We report a case of CNS large T-cell lymphoma presenting as multiple cerebral lesions in a patient with a history of MF. Methods. We report a case of a 33-year-old woman, known since the age of 16 for erythematous plaques thought to be atopic dermatitis, who developed, end 2012, multiple nodular skin lesions and peripheral adenopathies. Two skin lesions were biopsied simultaneously, and diagnosed as MF and tMF. A lymph node biopsy showed dermatopathic changes without lymphoma (Stage IIB). She received local treatment (UVB, PUVA and radiation therapy) and interferon therapy, and experienced almost complete remission. In 2015 neurological symptoms lead to evidence multiple cerebral lesions, suspicious for lymphoma, evaluated by stereotaxic biopsies. We compared histopathological and molecular features of these with previous skin specimens. After negative bone marrow staging biopsy, she was recently started on chemotherapy (MATRIX). Short follow-up shows rapidly worsening clinical conditions. Results. One of the initial skin biopsies showed atypical lymphoid cells with epidermotropism, Pautrier abcesses and CD4+ CD30- phenotype; the other revealed diffuse dermal infiltration by predominantly large cerebriform tumor cells with high proliferative fraction, and CD2−CD3 −CD4+/−CD7−CD30+ALK- EMA- non-cytotoxic immunophenotype. Altogether, these results led us to diagnose MF and tMF, respectively. The brain was infiltrated by large atypical lymphoid cells with cerebriform nuclei, somewhat anaplastic features and perivascular distribution. By immunohistochemistry, tumor cells were highly proliferative, with a CD2−CD3+CD5−CD7+CD30+ activated cytotoxic immunophenotype. A diagnosis of CD30+ cytotoxic peripheral T-cell lymphoma was retained. TRG and TRB clonality analyses revealed clonal rearrangements in skin and CNS biopsies, with identical patterns in both skin specimens but only minimally overlapping profiles when compared to the CNS sample. Der Pathologe 6 ? 2015 | 633 Conclusions. The reported case illustrates an uncommon finding of a CNS T-cell lymphoma in a patient with previous MF, questioning the clonal relationship between the two diseases and challenging the adequate classification of this CNS lymphoma as either a progression or a de novo lymphoma. Despite differences in immunophenotype and clonality patterns, this CNS lymphoma could possibly represent an aggressive divergent evolution of a primary cutaneous T-cell lymphoma. Additional sequencing is ongoing to try to solve the question.

Screening and overdiagnosis : public health implications

Overdiagnosis is the diagnosis of an abnormality that bears no substantial health hazard and no benefit for patients to be aware of. Resulting mainly from the use of increasingly sensitive screening and diagnostic tests, as well as broadened definitions of conditions requiring an intervention, overdiagnosis is a growing but still largely misunderstood public health issue. Fear of missing a diagnosis or of litigation, financial incentives or patient's need of reassurance are further causes of overdiagnosis. The main consequence of overdiagnosis is overtreatment. Treating an overdiagnosed condition bears no benefit but can cause harms and generates costs. Overtreatment also diverts health professionals from caring for those most severely ill. Recognition of overdiagnosis due to screening is challenging since it is rarely identifiable at the individual level and difficult to quantify precisely at the population level. Overdiagnosis exists even for screening of proven efficacy and efficiency. Measures to reduce overdiagnosis due to screening include heightened sensitization of health professionals and patients, active surveillance and deferred treatment until early signs of disease progression and prognosis estimation through biomarkers (including molecular) profiling. Targeted screening and balanced information on its risk and benefits would also help limit overdiagnosis. Research is needed to assess the the public health burden and implications of overdiagnosis due to screening activity.

Screening for cardiovascular disease risk factors beginning in childhood

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Individual detection and intervention on CVD risk factors and behaviors throughout childhood and adolescence has been advocated as a strategy to reduce CVD risk in adulthood. The U.S. National Heart, Lung, and Blood Institute (NHLBI) has recently recommended universal screening of several risk factors in children and adolescents, at odds with several recommendations of the U.S. Services Task Force and of the U.K. National Screening committee. In the current review, we discuss the goals of screening for CVD risk factors (elevated blood pressure, abnormal blood lipids, diabetes) and behaviors (smoking) in children and appraise critically various screening recommendations. Our review suggests that there is no compelling evidence to recommend universal screening for elevated blood pressure, abnormal blood lipids, abnormal blood glucose, or smoking in children and adolescents. Targeted screening of these risk factors could be useful but specific screening strategies have to be evaluated. Research is needed to identify target populations, screening frequency, intervention, and follow-up. Meanwhile, efforts should rather focus on the primordial prevention of CVD risk factors and at maintaining a lifelong ideal cardiovascular health through environmental, policy, and educational approaches.

Phylogenetic relationships of Apodemus Kaup, 1829 (Rodentia: Muridae) species in the Eastern Mediterranean inferred from mitochondrial DNA, with emphasis on iranian species

Wood mice of the genus Apodemus are widely distributed in Eurasia, with the Eastern Mediterranean being considered as a hotspot. Indeed, numerous species have been documented in Iran, including A. witherbyi, A. hyrcanicus, A. uralensis, A. avicennicus, A. hermonensis, and A. arianus. In this study, 129 specimens were collected from different Iranian localities and two specimens from Afghanistan. The animals were identified taxonomically and their phylogenetic relationships were investigated using cytochrome b mitochondrial DNA sequences. Five species of the genus Apodemus were identified in Iran, including A. hyrcanicus, A. witherbyi, A. cf. ponticus, A. uralensis, and A. mystacinus, beside, A. pallipes from Afghanistan. This study found no evidence of A. flavicollis or A. sylvaticus in Iran, despite their occurrence in Turkey, shedding doubt on the status of A. flavicollis in Iran, Asia Minor, and the Levant. Phylogenetic analyses imply that A. witherbyi has priority over A. avicennicus, A. hermonensis, and A. iconicus. Estimation of the divergence time for these taxa suggests a separation at around 7.2 Ma for the subgenera Karstomys (including A. mystacinus and A. epimelas) and Sylvaemus (including A. flavicollis, A. sylvaticus, A. uralensis, A. pallipes, A. hyrcanicus, A. witherbyi, and A. cf. ponticus). Within the subgenus Karstomys, the divergence times for A. mystacinus and A. epimelas were between 3.0 and 6.1 Ma, and divergence times within the subgenus Sylvaemus were between 5.2 and 6.9 Ma for A. witherbyi and other species in this subgenus. It is postulated that vicariance events including the uplifting of the Zagros Mountains and Anatolian Plateau in the middle Miocene and climate oscillations during the Messinian Salinity Crisis besides formation of the Hyrcanian tertiary forests during the Neogene probably played substantial roles in the radiation and distribution of the genus Apodemus in the Eastern Mediterranean.

Relationship between sedimentation sign and morphological grade in symptomatic lumbar spinal stenosis.

PURPOSE: We aimed to study the relationship between two morphological parameters recently described on MRI images in relation to lumbar spinal stenosis (LSS): the first is the sedimentation sign (SedS) and the second is the morphological grading of lumbar stenosis. MATERIALS AND METHODS: MRIs from a total of 137 patients were studied. From those, 110 were issued from a prospective database of symptomatic LSS patients, of whom 73 were treated surgically and 37 conservatively based on symptom severity. A third group consisting of 27 subjects complaining of low back pain (LBP) served as control. Severity of stenosis was judged at disc level using the four A to D grade morphological classification. The presence of a SedS was judged at pedicle level, above or below the site of maximal stenosis. RESULTS: A positive SedS was observed in 58, 69 and 76 % of patients demonstrating B, C and D morphology, respectively, but in none with grade A morphology. The SedS was positive in 67 and 35 % of the surgically and conservatively treated patients, respectively, and in 8 % of the LBP group. C and D morphological grades were present in 97 and 35 % of patients in the surgically and conservatively treated group, respectively, and in 18 % of the LBP group. Presence of a positive SedS carried an increased risk of being submitted to surgery in the symptomatic LSS group (OR 3.5). This risk was even higher in the LSS patients demonstrating grade C or D morphology (OR 65). DISCUSSION AND CONCLUSION: One-third of surgically treated LSS patients do not present a SedS. This sign appears to be a lesser predictor of treatment modality in our setting of symptomatic LSS patients compared to the severity of stenosis judged by the morphological grade.

Introgressive hybridization of threatened European tree frogs (Hyla arborea) by introduced H. intermedia in Western Switzerland

Hybridization by introduced taxa is a major threat to native species. Characterizing human introductions is thus one of the missions of conservation geneticists. Here we survey a declining population of the regionally endangered European tree frog (Hyla arborea) in the Grangettes natural reserve (Rhone valley, Western Switzerland), where previous evidence indicated human introduction of the Italian taxon H. intermedia. We combined fast-evolving mitochondrial and nuclear markers and an extended sampling to conduct population genetic analyses of the Grangettes and putative source areas. We show that the Grangettes population is a hybrid swarm, with all individuals featuring recent nuclear admixture and mitochondrial DNA of introduced H. intermedia, most likely of proximate south Alpine origin. In contrast, H. arborea and H. intermedia hardly introgress in their natural parapatric ranges, consistent with an advanced reproductive isolation. Thus, potential hybrid incompatibilities may account for the strong decline of this population, despite important conservation efforts. Although their hybrid nature makes them a priori unworthy of any protection, we propose specific measures to recover local H. arborea gene pool and preserve tree frogs in the Grangettes, the last population remaining from this heavily impacted part of the Alps.

Outcomes After Liver Resection for Hepatic Alveolar Echinococcosis: A Single-Center Cohort Study.

BACKGROUND: Switzerland is a region in which alveolar echinococcosis (AE) is endemic. Studies evaluating outcomes after liver resection (LR) for AE are scarce. The aim of this study was to assess the short- and long-term outcomes of AE patients after LR in a single tertiary referral center. METHODS: We retrospectively analyzed data pertaining to all patients with liver AE who were treated with LR at our institution between January 1992 and December 2013. Patient demographics, intraoperative data, extent of LR procedures (major vs. minor LR), postoperative outcomes, and negative histological margin (R0) resection rate were recorded in a database. Recurrence rates after LR were analyzed. RESULTS: LR was performed in 59 patients diagnosed with hepatic AE (56 complete surgeries, 3 reduction surgeries). Postoperative morbidity and mortality were observed in 34 % (25 % grade I-II, 9 % grade III-IV) and 2 % of the patients, respectively. R0 (complete) resection rate was 71 % (n = 42), and R1/R2 resection rate was 29 % (n = 17). Extra-hepatic recurrence occurred in 1 case (lung) after R0 resection. In cases of R1/R2 resection, 7 intra-hepatic disease progressions occurred with a median time of 10 months (IQR 6-11 months). Long-term (more than 1 year) benzimidazole treatment stabilized the disease in 64 % (9/14) of patients with R1 status. The overall survival rate was 97 %. CONCLUSIONS: Liver AE can be safely and definitively treated with LR, provided that R0 resection is achieved. In cases of R1 resection, benzimidazole therapy seems to be effective in stabilizing the intra-hepatic disease and preventing extra-hepatic recurrence.

Association of car ownership and physical activity across the spectrum of human development : Modeling the Epidemiologic Transition Study (METS).

BACKGROUND: Variations in physical activity (PA) across nations may be driven by socioeconomic position. As national incomes increase, car ownership becomes within reach of more individuals. This report characterizes associations between car ownership and PA in African-origin populations across 5 sites at different levels of economic development and with different transportation infrastructures: US, Seychelles, Jamaica, South Africa, and Ghana. METHODS: Twenty-five hundred adults, ages 25-45, were enrolled in the study. A total of 2,101 subjects had valid accelerometer-based PA measures (reported as average daily duration of moderate to vigorous PA, MVPA) and complete socioeconomic information. Our primary exposure of interest was whether the household owned a car. We adjusted for socioeconomic position using household income and ownership of common goods. RESULTS: Overall, PA levels did not vary largely between sites, with highest levels in South Africa, lowest in the US. Across all sites, greater PA was consistently associated with male gender, fewer years of education, manual occupations, lower income, and owning fewer material goods. We found heterogeneity across sites in car ownership: after adjustment for confounders, car owners in the US had 24.3 fewer minutes of MVPA compared to non-car owners in the US (20.7 vs. 45.1 minutes/day of MVPA); in the non-US sites, car-owners had an average of 9.7 fewer minutes of MVPA than non-car owners (24.9 vs. 34.6 minutes/day of MVPA). CONCLUSIONS: PA levels are similar across all study sites except Jamaica, despite very different levels of socioeconomic development. Not owning a car in the US is associated with especially high levels of MVPA. As car ownership becomes prevalent in the developing world, strategies to promote alternative forms of active transit may become important.