Pathology of pancreatic ductal adenocarcinoma: Facts,challenges and future developments

Despite major improvements concerning its diagnosis and treatment, pancreatic ductal adenocarcinoma (PDAC) remains an aggressive disease with an extremely poor prognosis. Pathology, as interface discipline between basic and clinical medicine, has substantially contributed to the recent developments and has laid the basis for further progress. The definition and classification of precursor lesions of PDAC and their molecular characterization is a fundamental step for the potential identification of biomarkers and the development of imaging methods for early detection. In addition, by integrating findings in humans with the knowledge acquired through the investigation of transgenic mouse models for PDAC, a new model for pancreatic carcinogenesis has been proposed and partially validated in individuals with genetic predisposition for PDAC. The introduction and validation of a standardized system for pathology reporting based on the axial slicing technique has shown that most pancreatic cancer resections are R1 resections and that this is due to inherent anatomical and biological properties of PDAC. This standardized assessment of prognostic relevant parameters represents the basis for the successful conduction of multicentric studies and for the interpretation of their results. Finally, recent studies have shown that distinct molecular subtypes of PDAC exist and are associated with different prognosis and therapy response. The prospective validation of these results and the integration of molecular analyses in a comprehensive pathology report in the context of individualised cancer therapy represent a major challenge for the future.     

Pulmonary,renal and neurological comorbidities in patients with ankylosing spondylitis; implications for clinical practice

Ankylosing spondylitis (AS) is associated with several comorbidities which contribute significantly to morbidity and mortality and add to the complexity of management. In addition to the well known extra-articular manifestations and increased cardiovascular risk, several pulmonary, renal, and neurological complications which have been associated with AS deserve equal attention. Whereas a clear link has been established for some manifestations, the evidence for other associations is less clear. Interstitial lung disease, apical fibrosis, secondary infection, and ventilatory restriction from reduced chest wall movement are well known pulmonary complications; more recently an association with sleep apnoea has been suggested. Renal amyloidosis and IgA nephropathy remain a treatment challenge which may respond to anti-TNF therapy. Atlanto axial subluxation and vertebral fractures can result in serious neurological complications and are notoriously difficult to diagnose unless a high level of suspicion is maintained. Despite several reports linking AS with demyelination a true link remains to be proved. This review discusses the prevalence, pathophysiology, and management of pulmonary, renal, and neurological complications, and implications for clinical practice.     

Time in hemodialysis modulates the levels of genetic damage in hemodialysis patients

It is assumed that hemodialysis treatment can diminish the levels of genetic damage in circulating lymphocytes by cleaning the blood of uremic toxins that cause oxidative stress. However, the hemodialysis process by itself may also induce genomic damage by producing reactive oxygen species (ROS). We conducted a follow‐up study in a group of 70 hemodialysis patients followed for a mean time of 15 months. We investigated the effect of exposure time in hemodialysis on the levels of genetic damage in peripheral blood lymphocytes using the micronucleus assay. In addition, genetic damage after in vitro irradiation with 0.5 Gy was also analyzed to evaluate changes in radiosensitivity. Our results showed that, at the end of the study, there was a decrease in both the basal levels of genetic damage (9.9 ± 1.0 vs. 7.6 ± 0.7) and radiosensitivity values (38.5 ± 3.0 vs. 27.6 ± 2.4). We conclude that hemodialysis procedures may act as an ameliorating factor reducing the genetic damage present in chronic kidney disease patients. Environ. Mol. Mutagen. 55:363–368, 2014. © 2014 Wiley Periodicals, Inc.     

Toxoplasma prevalence among pregnant women in Norway: a cross‐sectional study

Infection by Toxoplasma gondii may lead to complications in the foetus if the mother suffers from primary infection during pregnancy . Previously infected women have produced toxoplasma‐specific IgG antibodies. The most recent study on prevalence of toxoplasma IgG in the Norwegian pregnant population was conducted 20 years ago. The present study is part of a research programme initiated by the Norwegian Institute of Public Health. We aimed to update the knowledge regarding the prevalence of toxoplasma IgG among pregnant women in Norway. In this cross‐sectional study, sera from 1922 pregnant women in Buskerud (992) and Sør‐Trøndelag counties (930) in Norway were collected consecutively. The presence of toxoplasma IgG was identified by values ≥8 IU/mL using an ELISA test. The overall prevalence of toxoplasma IgG seropositivity was 9.3% (95% CI 8.1–10.7); Sør‐Trøndelag 10.4% (95% CI 8.6–12.6) and Buskerud 8.3% (95% CI 6.7–10.2). There was no difference between the counties (p = 0.13), and the result did not differ from prevalences found in 1974 (12.1%) and 1994 (10.7%). We found a higher prevalence among women ≥40 years (OR 2.65, 95% CI 1.30–5.42). The prevalence of toxoplasma IgG among pregnant women in Norway is low and has been stable during the last decades.     

Genomic damage as a biomarker of chronic kidney disease status

Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer and cardiovascular diseases, as well as high levels of genomic damage. To confirm the association of CKD with genomic damage we have carried out the largest study to date addressing this issue, using a total of 602 subjects (187 controls, 206 pre‐dialysis CKD patients and 209 CKD patients in hemodialysis). DNA oxidative damage was measured in all individuals using the comet assay. Our results indicate that CKD patients have significantly higher levels of DNA damage than controls, but no significant differences were observed between pre‐hemodialysis (pre‐HD) and hemodialysis (HD) patients. When oxidative damage was measured, no differences were observed between patients and controls, although HD patients showed significantly higher levels of oxidative damage than pre‐HD patients. In addition, a positive relationship was demonstrated between genomic damage and all‐cause mortality. Our study confirms that genomic damage can be predictive of prognosis in CKD patients, with high levels of DNA damage indicating a poor prognosis in HD patients. Environ. Mol. Mutagen. 56:301–312, 2015. © 2014 Wiley Periodicals, Inc.     

Sensitivity and specificity of patient-entered red flags for lower back pain

Background Context

Red flags are questions typically ascertained by providers to screen for serious underlying spinal pathologies. The utility of patient-reported red flags in guiding clinical decision-making for spine care, however, has not been studied.

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

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