Hypothyroidism Is a Risk Factor for New-Onset Diabetes: A Cohort Study

OBJECTIVE To identify risk factors for the development of statin-associated diabetes mellitus (DM). RESEARCH DESIGN AND METHODS The study was conducted in two phases. Phase one involved high-throughput in silico processing of a large amount of biomedical data to identify risk factors for the development of statin-associated DM. In phase two, the most prominent risk factor identified was confirmed in an observational cohort study at Clalit, the largest health care organization in Israel. Time-dependent Poisson regression multivariable models were performed to assess rate ratios (RRs) with 95% CIs for DM occurrence. RESULTS A total of 39,263 statin nonusers were matched by propensity score to 20,334 highly compliant statin initiators in 2004–2005 and followed until the end of 2010. Within 59,597 statin users and nonusers in a multivariable model, hypothyroidism and subclinical hypothyroidism carried an increased risk for DM (RR 1.53 [95% CI 1.31–1.79] and 1.75 [1.40–2.18], respectively). Hypothyroidism increased DM risk irrespective of statin treatment (RR 2.06 [1.42–2.99] and 1.66 [1.05–2.64] in statin users and nonusers, respectively). Subclinical hypothyroidism risk for DM was prominent only upon statin use (RR 1.94 [1.13–3.34] and 1.20 [0.52–2.75] in statin users and nonusers, respectively). Patients with hypothyroidism treated with thyroid hormone replacement therapy were not at increased risk for DM. CONCLUSIONS Hypothyroidism is a risk factor for DM. Subclinical hypothyroidism-associated risk for DM is prominent only upon statin use. Identifying and treating hypothyroidism and subclinical hypothyroidism might reduce DM risk. Future clinical studies are needed to confirm the findings. </jats:sec

Sensations and reaction times evoked by electrical sinusoidal stimulation

Objective. - To determine whether 5 Hz and 2000 Hz sinusoidal electric currents evoke different sensations and to indirectly evaluate which peripheral nerve fibers are stimulated by these different frequencies.Methods. - One hundred and fifty subjects chose three among eight descriptors of sensations evoked by 5 Hz and 2000 Hz currents and the results were submitted to factor analysis. in 20 reaction times to 5, 250 and 2000 Hz currents were determined at 1.1xST and reaction subjects, times to 5 Hz currents were also determined at 2xST.Results. - Responses were grouped in four factors: Factor 1, which loaded mainly in descriptors related to tweezers stimulation, was higher than the other factors during 2000 Hz stimulation at 1.5xST. Factor 2, which loaded mainly in descriptors related to needle stimulation, was higher than the other factors during 5 Hz stimulation. Factor 1 increased and Factor 2 decreased with an increase in 5 Hz intensity from 1.5 to 4xST. Reaction times measured from the fastest responses were significantly different: 0.57 s (0.16 to 1.60), 0.34 s (0.12 to 0.71) and 0.22 s (0.08 to 0.35) for 5, 250 and 2000 Hz, respectively, and 0.22 s (0.11 to 0.34) for 5 Hz at 2xST.Conclusions. - Sinusoidal electrical stimulation of 5 Hz and 2000 Hz evoke different sensations. At juxta-threshold intensities, RT measurements suggest that 2000 Hz stimulates A beta-fibers, 250 Hz A beta- or A partial derivative-fibers, 5 Hz A beta-, A partial derivative- or C-fibers. the fiber type, which was initially stimulated by the lower frequencies, depended on inter-individual differences. (C) 2009 Elsevier Masson SAS. All rights reserved.Universidade Federal de São Paulo, BR-04120050 São Paulo, BrazilUniversidade Federal de São Paulo, EPM, BR-04120050 São Paulo, BrazilWeb of ScienceFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 05337-6CNPq: 478476/2004-

Article: Breast cancer polygenic risk scores derived in White European populations are not calibrated for women of Ashkenazi Jewish descent.

PURPOSE: Polygenic risk scores (PRS) are a major component of accurate breast cancer (BC) risk prediction but require ethnicity-specific calibration. Ashkenazi-Jews-(AJ) are assumed to be of White-European-(WE) origin in some commercially-available PRS despite differing effect-allele-frequencies-(EAFs). We conducted a case-control study of WE and AJ women from the PROCAS-(Predicting-Risk-of-Cancer-at-Screening) study. The BCINIS-(Breast-Cancer-in-Northern-Israel-study) provided a separate AJ population-based case-control validation series. METHODS: All women underwent Illumina Oncoarray SNP-analysis. Two PRS were assessed, SNP142&SNP78. 221/2243 WE (Discovery:cases=111;controls=110;Validation:cases=651;controls=1772) and 221 AJ (cases=121;controls=110) women were included from the UK study; the Israeli series consisted of 2045 AJ women (cases=1331;controls=714). EAFs were obtained from gnomAD. RESULTS: In the UK study the mean SNP142PRS demonstrated good calibration and discrimination in WEs: mean PRS in cases=1.33-(95%CI=1.18-1.48) and controls=1.01-(95%CI=0.89-1.13). In AJs from Manchester, the mean PRS in cases=1.54-(1.38-1.70) and controls=1.20-(1.08-1.32) demonstrated good discrimination but overestimation of BC relative-risk. After adjusting for AJ EAFs, mean risk was corrected (mean SNP142-PRS cases=1.30-(95%CI=1.16-1.44) and controls=1.02-(95%CI=0.92-1.12)). This was recapitulated in the larger Israeli dataset with good discrimination (AUC=0.632-(95%CI=0.607-0.657) for SNP142). CONCLUSION: AJ women should not be given BC relative-risk predictions based on PRS calibrated to EAFs from WEs. PRS need to be recalibrated using AJ-derived-EAFs. A simple recalibration using the mean PRS adjustment ratio likely performs well

If it is in the marrow, is it also in the blood? An analysis of 1,000 paired samples from patients with B-cell non-Hodgkin lymphoma

<p>Abstract</p> <p>Background</p> <p>Staging of B-cell non Hodgkin's lymphoma (NHL) routinely involves bone marrow (BM) examination by trephine biopsy (BM-TB). The evidence of disease in the BM-TB results in a clinical stage IV classification affecting therapeutic strategies for NHL patients. BM immunophenotyping by flow cytometry (FC) is also used, although its clinical value is still under debate.</p> <p>Methods</p> <p>Using FC we analyzed 1,000 paired BM aspirates and peripheral blood (PB) samples from 591 NHL patients to investigate the concordance between BM and PB. B-lymphocytes were defined monoclonal when a ratio of 0.3 < κ/l > 3 was observed. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. BM-TB was also performed in 84.1% of samples (841/1000), and concordance between BM-TB and BM-FC was evaluated. Concordance was defined as the presence of a positive (in terms of disease detection) or negative result in both BM-FC and PB-FC or BM-TB and BM-FC.</p> <p>Results</p> <p>Using FC, the overall concordance between BM and PB was 95%. Among the discordant cases (ie presence of neoplastic B-lymphocyte in the BM but under the sensibility of the technique in the PB) the most frequent diagnosis was Waldenstrom's macroglobulinemia (WM, accounting for 20.8% of all discordant cases). The expression of CXCR4, a receptor involved in B-cell trafficking and homing, was found to be down regulated in WM compared to other NHL types, thus suggesting a possible role of CXCR4 in WM cell homing in the BM. WM excluded, FC investigation of BM and PB in NHL patients gives overlapping information.</p> <p>BM involvement was observed by FC in 38% of samples, and concordance between BM-FC and BM-TB was 85%.</p> <p>Conclusions</p> <p>The finding that FC data from BM and PB samples overlap in NHL might have major implications for the design of future clinical studies and for patients' follow-up.</p