Tympanostomy tubes improve hearing at 1 to 3 months compared with watchful waiting, with no evidence of benefit by 12 to 24 months. Children with recurrent acute otitis media may have fewer episodes after tympanostomy tube placement, but the evidence base is severely limited. The benefits of tympanostomy tubes must be weighed against a variety of associated adverse events.
g u i d e l i n e s u m m a r y Kidney International (2018) 94, 663-673 Algorithm 1 | Treatment scheme for chronic kidney disease (CKD) G1 to G5D. (See Algorithm 2 for kidney transplant recipients.) Recommendation grades (1À2) and strength of evidence (AÀD) are provided for each recommended treatment regimen and hepatitis C virus (HCV) genotype; see full guideline. 1 DAA, direct-acting antiviral; GFR, glomerular filtration rate; NAT, nucleic acid testing. M Jadoul et al.: Summary of 2018 KDIGO HCV in CKD Guideline g u i d e l i n e s u m m a r y Kidney International (2018) 94, 663-673 g u i d e l i n e s u m m a r y M Jadoul et al.: Summary of 2018 KDIGO HCV in CKD Guideline
KRAS mutations have been established as a major predictive biomarker for resistance to the treatment of metastatic colorectal cancer (mCRC) with anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR MoAbs). However, many patients with KRAS wild-type tumors still do not respond to the treatment. We conducted a systematic review with meta-analysis to assess whether BRAF mutations, PIK3CA mutations and PTEN loss can predict the outcomes of patients with KRAS wild-type mCRC treated with anti-EGFR MoAbs. Studies that explored the association of one or more of the three biomarkers with progression-free survival (PFS), overall survival (OS) and/or objective response rate (ORR) were identified through August 2012. Summary hazard ratios (HRs) and rate differences (RDs) and corresponding 95% confidence intervals (CIs) were calculated by using the random-effects model. BRAF mutations, PIK3CA exon 20 mutations and PTEN loss were all associated with shorter PFS (HR 5 2.59, 95% CI 1.67-4.03; HR 5 2.52, 95% CI 1.33-4.78 and HR 5 1.75, 95% CI 1.19-2.56, respectively), shorter OS (HR 5 2.74, 95% CI 1.79-4.19; HR 5 3.29, 95% CI 1.60-6.75 and HR 5 1.85, 95% CI 1.30-2.64, respectively) and lower ORR (RD 5 236%, 95% CI 244 to 228%; RD 5 238%, 95% CI 251 to 224% and RD 5 241%, 95% CI 268 to 214%, respectively). PIK3CA exon 9 mutations were associated with none of the outcomes. Studies with relevant data consistently demonstrated a stronger predictive power of combined multiple biomarkers as compared to one alteration alone. These results suggest that BRAF mutations, PIK3CA exon 20 mutations and PTEN loss are predictive of better outcomes in KRAS wild-type mCRC treated with anti-EGFR MoAbs. However, the quality of included studies varied, and some of the meta-analyses were limited by significant between-study heterogeneity. In the future, well-designed large randomized controlled trials conducted in KRAS wild-type mCRC patients with subgroup analysis according to BRAF, PIK3CA exon 20 and PTEN status are essential to fully assess the clinical relevance of these biomarkers.Colorectal cancer (CRC) is the third most common malignant disease and the fourth leading cause of cancer-related deaths worldwide.1 Metastatic CRC (mCRC) is associated with a particular poor prognosis. Despite progress in chemotherapy during past decades, the five-year survival rate of patients with mCRC remains below 10%.2 Recently, two monoclonal antibodies (MoAbs) targeted at epidermal growth factor receptor (EGFR), the chimeric IgG1 MoAb cetuximab
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