Medicine
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Review Meta Analysis
BRAF mutation in papillary thyroid cancer and its value in tailoring initial treatment: a systematic review and meta-analysis.
Clinicians have long sought to characterize biological markers of neoplasia as objective indicators of tumor presence, pathogenicity, and prognosis. Armed with data that correlate biomarker activity with disease presence and progression, clinicians can develop treatment strategies that address risks of disease recurrence or persistence and progression. The B-type Raf kinase (BRAF V600E) mutation in exon 15 of the BRAF gene has been noted to be a putative prognostic marker of the most prevalent form of thyroid cancer, papillary thyroid cancer (PTC)--a tumor type with high proclivity for recurrence or persistence. ⋯ The risk ratios in BRAF mutation-positive patients were 1.93 (95% confidence interval [CI], 1.61-2.32; Z = 7.01; p < 0.00001) for PTC recurrence, 1.32 (95% CI, 1.20-1.45; Z = 5.73; p < 0.00001) for lymph node metastasis, 1.71 (95% CI, 1.50-1.94; Z = 8.09; p < 0.00001) for extrathyroidal extension, 0.95 (95% CI, 0.63-1.44; Z = 0.23; p = 0.82) for distant metastasis, and 1.70 (95% CI, 1.45-1.99; Z = 6.46; p < 0.00001) for advanced stage AJCC III/IV. Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV. Patients with PTC harboring mutated BRAF are likely to demonstrate factors that are associated with an increased risk for recurrence of the disease, offering new prospects for optimizing and tailoring initial treatment strategies to prevent recurrence.
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Cochlear implants allow individuals with severe to profound hearing loss access to sound and spoken language. The number of older adults in the United States who are potential candidates for cochlear implantation (CI) is approximately 150,000 and will continue to increase with the aging of the population. Should CI be routinely recommended for these older adults, and do these individuals benefit from CI? We reviewed our 12-year experience with CI in adults aged ≥60 years (n = 445) at Johns Hopkins Medical Institutions to investigate the impact of CI on speech understanding and to identify factors associated with speech performance. ⋯ These results suggest that older adult CI candidates who are younger at implantation and with higher preoperative speech scores obtain the highest speech understanding scores after CI, with possible implications for current United States Medicare policy. Finally, we provide an extended discussion of the epidemiology and impact of hearing loss in older adults. Future research of CI in older adults should expand beyond simple speech outcomes to take into account the broad cognitive, social, and physical functioning outcomes that are likely detrimentally affected by hearing loss and may be mitigated by CI.
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Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73 yr). ⋯ Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases. Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD.
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Clinical Trial
Rituximab for the treatment of IgG4-related disease: lessons from 10 consecutive patients.
Patients with IgG4-related disease (IgG4-RD) typically have elevated serum concentrations of IgG4 and share histopathologic features that are similar across affected organ(s). IgG4-RD patients frequently require prolonged treatment with glucocorticoids and are often unable to taper these medications. Traditional disease-modifying antirheumatic drugs (DMARDs) are generally ineffective. ⋯ Treatment with RTX led to prompt clinical and serologic improvement in refractory IgG4-RD in all patients with active inflammation. Serial treatments with RTX may lead to progressive declines in serum IgG4 concentrations and better disease control. Serum IgG4 concentrations may remain low, and clinical disease activity may remain quiescent even after B cell reconstitution in a significant proportion of patients.
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Inappropriate initial antimicrobial therapy (IIAT) has been associated with decreased survival in patients with health care-associated pneumonia (HCAP). We performed a study to determine whether empiric HCAP antibiotic regimens targeting methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are associated with greater appropriate therapy. A retrospective cohort study of culture-positive HCAP over 6 years (January 2003-December 2008) was performed at Barnes-Jewish Hospital, a 1200-bed urban teaching hospital. ⋯ Multivariate logistic regression analysis demonstrated that empiric anti-pseudomonal antibiotics (adjusted odds ratio [AOR], 1.75; 95% confidence interval [CI], 1.34-2.29; p=0.036), empiric anti-MRSA antibiotics (AOR, 1.71; 95% CI, 1.36-2.14; p=0.018), infection with Streptococcus pneumoniae (AOR, 2.82; 95% CI, 2.03-3.91; p=0.002), absence of Acinetobacter species infection (AOR, 10.57; 95% CI, 7.29-15.33; p<0.001), absence of P. aeruginosa infection (AOR, 1.69; 95% CI, 1.36-2.05; p=0.014), and absence of Stenotrophomonas maltophilia infection (AOR, 20.43; 95% CI, 9.35-44.66; p<0.001) are independent predictors of appropriate therapy for HCAP. Our study suggests that initial therapy for HCAP should include antibiotics targeting MRSA and P. aeruginosa in order to provide appropriate initial therapy. However, the selection of individual antibiotic agents should be based on local patterns of infection and adjusted when microbiology results become available.