Citations

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

ABSTRACT Replication of negative-strand RNA viruses occurs in association with discrete cytoplasmic foci called inclusion bodies. Whereas inclusion bodies represent a prominent subcellular structure induced by viral infection, our knowledge of the cellular protein components involved in inclusion body formation and function is limited. Using measles virus-infected HeLa cells, we found that the WD repeat-containing protein 5 (WDR5), a subunit of histone H3 lysine 4 methyltransferases, was selectively recruited to virus-induced inclusion bodies. Furthermore, WDR5 was found in complexes containing viral proteins associated with RNA replication. WDR5 was not detected with mitochondria, stress granules, or other known secretory or endocytic compartments of infected cells. WDR5 deficiency decreased both viral protein production and infectious virus yields. Interferon production was modestly increased in WDR5-deficient cells. Thus, our study identifies WDR5 as a novel viral inclusion body-associated cellular protein and suggests a role for WDR5 in promoting viral replication. IMPORTANCE Measles virus is a human pathogen that remains a global concern, with more than 100,000 measles-related deaths annually despite the availability of an effective vaccine. As measles continues to cause significant morbidity and mortality, understanding the virus-host interactions at the molecular level that affect virus replication efficiency is important for development and optimization of treatment procedures. Measles virus is an RNA virus that encodes six genes and replicates in the cytoplasm of infected cells in discrete cytoplasmic replication bodies, though little is known of the biochemical nature of these structures. Here, we show that the cellular protein WDR5 is enriched in the cytoplasmic viral replication factories and enhances virus growth. WDR5-containing protein complex includes viral proteins responsible for viral RNA replication. Thus, we have identified WDR5 as a host factor that enhances the replication of measles virus.

Objectives: To describe the surgical treatment and patient outcomes of chronic elbow dislocations. Design: Retrospective review. Setting: Two tertiary referral centers. Patients/Participants: All patients with surgically treated chronic elbow dislocation with no associated articular fracture from January 2009 to January 2015. Intervention: Review of patient demographics, injury chronicity, surgical technique, and patient outcomes. Main Outcome Measurement: Clinical outcomes included elbow range of motion and complications. Radiographic outcomes included the presence of heterotopic ossification. Patient-reported outcomes included the Mayo Elbow Performance Index (MEPI) and the Summary Outcome Determination (SOD). Results: Thirty-two patients with mean follow-up of 22 months (range, 13–41 months) were included. The mean dislocation duration was 6 months (range, 1–34 months). The mean preoperative range of motion was 8 degrees (range, 0–30 degrees). There were no infections or recurrent dislocations. One patient developed transient ulnar nerve palsy postoperatively. There were no cases of new or progressive heterotopic ossification. The mean postoperative extension was 31 degrees (range, 0–75 degrees), and the mean postoperative flexion was 132 degrees (range, 95–150 degrees); the mean final arc of motion was 101 degrees (range, 50–140 degrees). The mean postoperative MEPI was 93 (range, 70–100), and the mean SOD score was 9 (range, 6–10). Using the MEPI, 97% (31/32 patients) had good or excellent outcome. There was no difference in flexion/extension arc or MEPI scores between groups of elbows older and younger than 17 years or dislocations less or more than 3 months. Conclusion: This is the largest case series of surgically treated patients with chronic elbow dislocation. Using our surgical technique, 97% of patients had good or excellent outcome with a low complication rate. Open reduction of chronic elbow dislocation can be accomplished while permitting early motion with minimal recurrent dislocation risk. Level of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND Numerous treatment modalities have been reported for squamous cell carcinoma in situ (SCCIS). Risk factors for recurrence have not been systematically reviewed. OBJECTIVE To systematically review and summarize the data on risk factors that contribute to recurrence of SCCIS. MATERIALS AND METHODS A PubMed search was completed using the terms “SCCIS,” “Bowen's disease,” “Bowen's disease and recurrence,” and “Bowen's disease and Mohs.” These sources were cross-referenced for the terms “treatment,” “management,” “therapy,” “recurrence,” and “margins.” Studies were selected on the basis of relevance and applicable treatments. RESULTS Immunosuppression was the only variable with a statistically signficant association with progression or recurrence of SCCIS. Although there were no data directly correlating subclinical lateral extension or invasive squamous cell carcinoma within SCCIS with recurrence, evidence supports both of these as common features of SCCIS. Other potential recurrence risk factors for which there are limited supporting data included tumor size, depth of follicular extension, and location. CONCLUSION Immunosuppression was the only risk factor associated with increased risk of tumor recurrence. Subclinical tumor extension and occult invasive squamous cell carcinoma are relatively common features that theoretically could increase recurrence risk. These factors should be considered when deciding upon treatment for SCCIS. Further study is required to quantify variables that influence recurrence and to identify optimal treatment options.

SummaryDue to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country‐specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

SummaryFactors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV‐related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high‐treatment rate will contribute to a reduction in total cases and HCV‐related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV‐related morbidity and mortality.

SummaryThe hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets—“WHO Targets” (65% reduction in HCV‐related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.