Incidental langerhans cell histiocytosis of thyroid: case report and review of the literature

We report a case of a 42-yr-old woman with Langerhans cell histiocytosis (LCH) confined to the thyroid and associated with lymphocytic thyroiditis and a papillary microcarcinoma. This patient remains free of symptoms 14 mo after surgery. Thyroid LCH is rare. In children, it usually occurs as part of a multisystemic disease, whereas it is usually exclusive in adults. Isolated thyroid LCH is frequently associated with another thyroid disease, especially lymphocytic thyroiditis, suggesting that it is a reactive process rather than a neoplastic proliferation. The prognosis of isolated thyroid LCH is good. However, because it can rarely precede or reveal a multisystemic disease, additional investigations as well as a prolonged follow-up are justified.     

Formalin-fixed and paraffin-embedded nodal non-Hodgkin's lymphomas demonstrate the same chromosome changes as those found in frozen samples: a comparative study using interphase fluorescence in situ hybridization.

Cytogenetic studies in lymphomas classically require fresh or frozen tissue, whereas in many instances only paraffin-embedded biopsies are available. We applied an interphase FISH assay on nuclei extracted from thick paraffin sections to determine accuracy of molecular cytogenetics in such samples. Twenty-three lymphoma samples and 4 reactive lymph nodes were tested with various commercially available DNA probes, and hybridization patterns were compared with those obtained on frozen nuclei counterparts. Successful hybridization with all probes tested was observed for 23/27 (85%) paraffin-embedded tissues and for all (100%) frozen samples, and cut-off levels defining positivity were superimposable for both situations. Chromosome changes were detected in the same way, without any false-positive or false-negative cases. Hybridization signals observed on dewaxed samples were either those classically expected to define the relevant chromosome change or were atypical: all atypical changes could be demonstrated also into nuclei from the frozen counterpart. Moreover, all typical and atypical chromosome changes observed on frozen nuclei were also detected in paraffin-embedded tissues. Our study shows that our interphase FISH assay performed on paraffin-embedded samples is a valuable alternate to conventional methods to ascertain diagnosis of lymphomas as to include patients into therapeutic trials.     

The influence of waiting times on cost-effectiveness: a case study of colorectal cancer mass screening

When a cost-effectiveness analysis is implemented, the health-care system is usually assumed to adjust smoothly to the proposed new strategy. However, technological innovations in health care may often induce friction in the organization of care supply, implying the congestion of services and subsequent waiting times. Our objective here is to measure how these short run rigidities can challenge cost-effectiveness recommendations favorable to an innovative mass screening test for colorectal cancer. Using Markov modeling, we compare the standard Guaiac fecal occult blood test (gFOBT) with an innovative screening test for colorectal cancer, namely the immunological fecal occult blood test (iFOBT). Waiting time can occur between a positive screening test and the subsequent confirmation colonoscopy. Five scenarios are considered for iFOBT: no further waiting time compared with gFOBT, twice as much waiting time for a period of 5 or 10 years, and twice as much waiting time for a period of 5 or 10 years combined with a 25 % decrease in participation to confirmation colonoscopies. According to our modeling, compared with gFOBT, iFOBT would approximately double colonoscopy demand. Probabilistic sensitivity analysis enables concluding that the waiting time significantly increases the uncertainty surrounding recommendations favorable to iFOBT if it induces a decrease in the adherence rate for confirmation colonoscopy.     

Effect of bipolar electrode orientation on local electrogram properties

1. Download high-res image (284KB)
2. Download full-size image

     

ABT-737 increases tyrosine kinase inhibitor-induced apoptosis in chronic myeloid leukemia cells through XIAP downregulation and sensitizes CD34(+) CD38(-) population to imatinib

Chronic myeloid leukemia (CML) tumorigenicity is driven by the oncogenic BCR-ABL tyrosine kinase. Specific tyrosine kinase inhibitors (TKI) have been designed and are now used for the treatment of CML. These TKI induce apoptosis in leukemic cells in a BIM-dependent mechanism. We hypothesized that an increase in BIM activity could sensitize CML cells to TKI. We blocked the anti-apoptotic proteins of the Bcl-2 family by using ABT-737, a Bcl-2 and Bcl-XL inhibitor. ABT-737 modified Bcl-2 protein interactions toward a pro-apoptotic phenotype. Its combination with TKI resulted in a strong synergism in CML cell lines. The association also induced a large decrease in X-linked inhibitor of apoptosis (XIAP), followed by caspase-3 activation. This XIAP decrease was due to post-translational events. The mitochondrial serine protease HtrA2/Omi was identified as being responsible for this off-target effect. Then, ABT-737 and TKI cooperate at several levels to induce apoptosis of CML cells lines, and the benefit of this association was also observed in CML hematopoietic progenitors. Interestingly, a lethal effect was also observed in the more immature CD34(+)CD38(-) TKI-insensitive population. Combination therapy might by an interesting strategy for the treatment of CML patients.     

ENIGMA-DTI: Translating reproducible white matter deficits into personalized vulnerability metrics in cross-diagnostic psychiatric research

The ENIGMA-DTI (diffusion tensor imaging) workgroup supports analyses that examine the effects of psychiatric, neurological, and developmental disorders on the white matter pathways of the human brain, as well as the effects of normal variation and its genetic associations. The seven ENIGMA disorder-oriented working groups used the ENIGMA-DTI workflow to derive patterns of deficits using coherent and coordinated analyses that model the disease effects across cohorts worldwide. This yielded the largest studies detailing patterns of white matter deficits in schizophrenia spectrum disorder (SSD), bipolar disorder (BD), major depressive disorder (MDD), obsessive–compulsive disorder (OCD), posttraumatic stress disorder (PTSD), traumatic brain injury (TBI), and 22q11 deletion syndrome. These deficit patterns are informative of the underlying neurobiology and reproducible in independent cohorts. We reviewed these findings, demonstrated their reproducibility in independent cohorts, and compared the deficit patterns across illnesses. We discussed translating ENIGMA-defined deficit patterns on the level of individual subjects using a metric called the regional vulnerability index (RVI), a correlation of an individual's brain metrics with the expected pattern for a disorder. We discussed the similarity in white matter deficit patterns among SSD, BD, MDD, and OCD and provided a rationale for using this index in cross-diagnostic neuropsychiatric research. We also discussed the difference in deficit patterns between idiopathic schizophrenia and 22q11 deletion syndrome, which is used as a developmental and genetic model of schizophrenia. Together, these findings highlight the importance of collaborative large-scale research to provide robust and reproducible effects that offer insights into individual vulnerability and cross-diagnosis features.