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01, p = .007) and albumin value (HR 0.26, beta -1.36 p = .001) were associated with liver mortality by competing risk analysis. SVR was associated with a reduced risk of cardiovascular mortality regardless of presence of cirrhosis (HR 0.07, beta-2.67, p less then .001). Presence of diabetes (HR 3.45, beta 1.24, p = .014) and chronic kidney disease class ≥3 (HR 3.60, beta 1.28, p = 0.016) were two factors independently associated with higher risk of cardiovascular mortality. Patients with SVR to a DAA therapy have a better liver and cardiovascular survival, and the effects of HCV eradication are most evident in patients with compensated liver disease.HER2 amplification, which results in overexpression of the receptor tyrosine kinase HER2, has been described in a wide variety of malignancies. A922500 datasheet HER2-targeting agents have been incorporated into the treatment paradigms for HER2-overexpressing breast and gastric cancer. More recently, these agents have shown promise in other gastrointestinal malignancies, such as colon cancer and biliary tract tumors. This study discusses two patients with gallbladder carcinoma and a third with ampullary carcinoma who were able to achieve marked responses to HER2-directed therapy. These cases underscore the importance of molecular analysis for HER2 amplification/HER2 overexpression, irrespective of tumor histology, and highlight a need for further investigation of HER2-directed therapy beyond breast and gastroesophageal cancers. KEY POINTS Current guidelines recommend molecular assessment for HER2 overexpression exclusively in breast and gastric adenocarcinoma. The focus of this report is on three cases (two biliary tract and one ampullary carcinoma) in which amplification of HER2 or overexpression of HER2 was detected and treatment with HER2-directed therapy resulted in robust responses. These cases exemplify responsiveness of non-breast/gastric histologies to HER2-directed therapies, highlighting several promising new settings for these agents. Testing for amplification of HER2 or overexpression of HER2 should be considered especially in rare diseases with limited treatment options.Ecological processes often exhibit time lags. For plant invasions, lags of decades to centuries between species' introduction and establishment in the wild (naturalisation) are common, leading to the idea of an invasion debt accelerating rates of introduction result in an expanding pool of introduced species that will naturalise in the future. Here, I show how a concept from survival analysis, the hazard function, provides an intuitive way to understand and forecast time lags. For plant naturalisation, theoretical arguments predict that lags between introduction and naturalisation will have a unimodal distribution, and that increasing horticultural activity will cause the mean and variance of lag times to decline over time. These predictions were supported by data on introduction and naturalisation dates for plant species introduced to Britain. While increasing trade and horticultural activity can generate an invasion debt by accelerating introductions, the same processes could lower that debt by reducing lag times.

The effectiveness and safety of peginterferon alpha (peg-IFN-α) monotherapy in inactive hepatitis B virus (HBV) carriers (IHCs) have not been fully evaluated.

This observational study prospectively enrolled 298 IHCs in China from 2015 to 2019. Participants were given the right to choose to either receive peg-IFN-α monotherapy (treatment group, n=142) or be monitored without treatment (control group, n=156) according to their wishes. The scheduled treatment duration was 48weeks. All participants were followed up to 72weeks. The main efficacy endpoint was hepatitis B surface antigen (HBsAg) clearance at 72weeks.

Baseline characteristics were similar between both groups. At 72weeks, intention-to-treat analysis showed that the rates of HBsAg clearance and seroconversion of the treatment group were 47.9% (68/142) and 36.6% (52/142), respectively, which were significantly higher than the HBsAg clearance rate of 1.9% (3/156) and the seroconversion rate of 0.6% (1/156) in the control group (both P<.001). Baseline HBV DNA<20IU/mL, lower HBsAg levels at baseline, 12 and 24weeks, alanine aminotransferase elevation at 12weeks, and greater HBsAg reduction from baseline to 12 and 24weeks were independent predictors of HBsAg clearance. Generally, the therapy was well tolerated. Only five participants discontinued therapy as a result of peg-IFNα-related adverse events.

Peg-IFN-α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.

Peg-IFN-α monotherapy results in high rates of HBsAg clearance and seroconversion and the treatment is safe for IHCs.The study aimed to assess the effect of an electronic medical record-embedded best practice alert (BPA) on HCV age cohort screening in primary care clinics. HCV testing by primary care physicians was monitored prior and subsequent to the implantation of the BPA. Four intervals of 9 months duration were analysed in detail, including a pre-BPA baseline analysis and three annual post-BPA assessments. Pre- and post-BPA orders consistently followed a power law distribution, characterized by small groups of physicians placing the majority of test orders. Significant correlations were present between the numbers of tests orders by each physician, suggesting that 'high' and 'low' screening performances tended to be physician-specific. Testing rates increased markedly in response to the BPA, resulting in completion of screening in 56.8% (50,468 of 88,914%) of the entire age cohort within less than 3 years. In conclusion, HCV age cohort testing by primary care physicians follows a power-law distribution, with high-performing physicians contributing disproportionately to the overall effort. A simple BPA resulted in a sufficient increase in testing to allow testing of the entire target population within a reasonable time frame.

We aimed to identify clinicopathological and molecular features associated with progression-free survival (PFS) and overall survival (OS) after pulmonary metastasectomy for metastatic colorectal cancer in a retrospective cohort in Brazil.

We did a retrospective review of thoracic surgeries performed in a single large academic hospital in Brazil from January 1985 to September 2019. Demographics, previously described prognostic factors, and clinicopathological and molecular characteristics were abstracted. Univariate Cox regression was performed for each variable, and, when significant, data were dichotomized to provide clinically meaningful thresholds.

Records from 698 patients were reviewed. Fifty-eight patients underwent pulmonary metastasectomy with curative intent. Of those, 53.4% had a single metastatic lesion. The median size of the largest lesion was 1.5 cm. Results of RAS, RAF, and mismatch repair testing and of cytokeratin 20 (CK20) and CDX2 testing were available for 13.8% and 58.6% of the sample, respectively.