Medical history of chemotherapy or immunosuppressive drug treatment and risk of amyotrophic lateral sclerosis (ALS)

A recent population-based analysis demonstrated lower risk of the lethal degenerative neuromuscular disease, amyotrophic lateral sclerosis (ALS) associated with history of the use of ‘antineoplastic agents’ and ‘immunosuppressants’. To see if this finding was generalizable to other ALS cohorts, we examined associations between use of these agents and ALS risk in an independent case–control study of n = 414 ALS patients and n = 361 controls in an Eastern US population. Controls were sampled from the general population and among non-neurodegenerative disease patients. A history of chemotherapy treatment was significantly associated with a decreased ALS risk (OR 0.46, 95% CI 0.22–0.89, P = 0.026). We did not observe an association between risk of ALS and immunosuppressant therapy use (OR 0.78, 95% CI 0.50–1.02, P = 0.23). Analyses were adjusted for age, gender, and smoking. Our results support the prior report for chemotherapy treatment and lead to further discussion of the underlying mechanism.     

Finding nemo: imaging findings, pitfalls, and complications of ingested fish bones in the alimentary canal

In Asian cuisine, fish is often prepared whole with the bones. Accidental fish bone (FB) ingestion is not an infrequently encountered condition in the emergency department. An impacted FB in the alimentary canal can lead to potentially life-threatening complications. For impacted FBs that cannot be visualized clinically, radiographs and multidetector computed tomography are helpful in localizing the FB, evaluating for complications, and planning treatment. In this pictorial essay, we illustrate the spectrum of radiological findings of impacted FBs, common imaging pitfalls, and complications. Finally, we highlight the imaging findings that are important to the clinician in planning treatment.     

Polymorphisms in the XRCC1 gene modify survival of bladder cancer patients treated with chemotherapy

Survival of bladder cancer patients depends on several factors including disease stage and grade at diagnosis, age, health status of the patient and the applied treatment. Several studies investigated the role of DNA repair genetic variants in cancer susceptibility, but only few studies investigated their role in survival and response to chemotherapy for bladder cancer. We genotyped 28 single nucleotide polymorphisms (SNP) in DNA repair genes in 456 bladder cancer patients, reconstructed haplotypes and calculated a score for combinations of the SNPs. We estimated Hazard Ratios (adjHR) for time to death. Among patients treated with chemotherapy, variant alleles of five SNPs in the XRCC1 gene conferred better survival (rs915927 adjHR 0.55 (95%CI 0.32–0.94); rs76507 adjHR 0.48 (95%CI 0.27–0.84); rs2854501 adjHR 0.25 (95%CI 0.12–0.52); rs2854509 adjHR 0.21 (95%CI 0.09–0.46); rs3213255 adjHR 0.46 (95%CI 0.26–0.80). In this group of patients, an increasing number of variant alleles in a XRCC1 gene score were associated with a better survival (26% decrease of risk of death for each additional variant allele in XRCC1). By functional analyses we demonstrated that the previous XRCC1 SNPs confer lower DNA repair capacity. This may support the hypothesis that survival in these patients may be modulated by the different DNA repair capacity determined by genetic variants. Chemotherapy treated cancer patients bearing an increasing number of “risky” alleles in XRCC1 gene had a better survival, suggesting that a proficient DNA repair may result in resistance to therapy and shorter survival. This finding may have clinical implications for the choice of therapy.     

Mandibular implant-retained overdenture with magnets: a case report

Implant-retained overdentures can be a simple treatment option to restore the edentulous mandible. Retention can be achieved via studs, linked bar system or magnets. Success rates using the different retention mechanisms have been reported to be high. However, long-term prospective studies on implant-retained overdentures are limited. This paper reports on a patient who has successfully worn a mandibular implant-retained overdenture with magnets for 12 years.     

Use of deferiprone for iron chelation in patients with transfusion-dependent thalassaemia

Aim: To conduct a retrospective case analysis of the clinical efficacy and adverse effects of deferiprone in our population. Methods: All patients with transfusion‐dependent thalassaemia at KK Hospital who have been on deferiprone were included in the study. Outcomes measured include the change in ferritin levels and cardiac T2* values during deferiprone therapy, and incidence of side effects. Results: Thirty‐three (47.1%) of the total cohort of 70 patients have been on deferiprone, out of which 26 were on combination therapy with desferrioxamine. Majority of the patients (76%) had stable cardiac iron load during deferiprone therapy, and four patients with moderate to severe cardiac iron load showed improvement. Ten patients (30.3%) had improvement in their ferritin levels. Three patients (9.1%) developed mild neutropenia at 3, 18 and 26 months, respectively, and two patients (6.1%) had agranulocytosis at 4 and 10 months, respectively. Their neutrophil counts improved spontaneously after cessation of deferiprone. Thrombocytopenia developed in 27.3% of the patients and was transient in majority (77.8%) of the patients. Five patients (15.2%) developed arthritis that improved after cessation of deferiprone therapy, and one patient had transient arthralgia that resolved spontaneously. Three patients (9.1%) had nausea and abdominal pain. Conclusion: Deferiprone effectively reduced or stabilised cardiac iron load in our patients. Thrombocytopenia, arthropathy, neutropenia and agranulocytosis are the most important side effects. It is recommended that patients on deferiprone have their full blood counts monitored weekly for the first year of therapy and subsequently fortnightly as long as they are on deferiprone.     

MDCT evaluation of central airway and vascular complications of lung transplantation

OBJECTIVE: The purpose of this article is to illustrate the spectrum of central airway and vascular complications in lung transplantation using MDCT, with an emphasis on the usefulness of advanced postprocessing techniques. CONCLUSION: MDCT is an invaluable tool in the diagnosis, evaluation, and posttreatment assessment of central airway and vascular complications in lung transplant recipients. Advanced postprocessing techniques provide complementary information that is visually accessible and anatomically meaningful for the clinician.     

MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors

MicroRNAs (miRNAs) regulate gene expression. It has been suggested that obtaining miRNA expression profiles can improve classification, diagnostic, and prognostic information in oncology. Here, we sought to comprehensively identify the miRNAs that are overexpressed in lung cancer by conducting miRNA microarray expression profiling on normal lung versus adjacent lung cancers from transgenic mice. We found that miR-136, miR-376a, and miR-31 were each prominently overexpressed in murine lung cancers. Real-time RT-PCR and in situ hybridization (ISH) assays confirmed these miRNA expression profiles in paired normal-malignant lung tissues from mice and humans. Engineered knockdown of miR-31, but not other highlighted miRNAs, substantially repressed lung cancer cell growth and tumorigenicity in a dose-dependent manner. Using a bioinformatics approach, we identified miR-31 target mRNAs and independently confirmed them as direct targets in human and mouse lung cancer cell lines. These targets included the tumor-suppressive genes large tumor suppressor 2 (LATS2) and PP2A regulatory subunit B alpha isoform (PPP2R2A), and expression of each was augmented by miR-31 knockdown. Their engineered repression antagonized miR-31–mediated growth inhibition. Notably, miR-31 and these target mRNAs were inversely expressed in mouse and human lung cancers, underscoring their biologic relevance. The clinical relevance of miR-31 expression was further independently and comprehensively validated using an array containing normal and malignant human lung tissues. Together, these findings revealed that miR-31 acts as an oncogenic miRNA (oncomir) in lung cancer by targeting specific tumor suppressors for repression.