A novel immune prognostic index for stratification of high-risk patients with early breast cancer.

The prognostic value of current multigene assays for breast cancer is limited to hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Despite the prognostic significance of immune response-related genes in breast cancer, immune gene signatures have not been incorporated into most multigene assays. Here, using public gene expression microarray datasets, we classified breast cancer patients into three risk groups according to clinical risk and proliferation risk. We then developed the immune prognostic index based on expression of five immune response-related genes (TRAT1, IL2RB, CTLA4, IGHM and IL21R) and lymph node status to predict the risk of recurrence in the clinical and proliferation high-risk (CPH) group. The 10-year probability of disease-free survival (DFS) or distant metastasis-free survival (DMFS) of patients classified as high risk according to the immune prognostic index was significantly lower than those of patients classified as intermediate or low risk. Multivariate analysis revealed that the index is an independent prognostic factor for DFS or DMFS. Moreover, the C-index revealed that it is superior to clinicopathological variables for predicting prognosis. Its prognostic significance was also validated in independent datasets. The immune prognostic index identified low-risk patients among patients classified as CPH, regardless of the molecular subtype of breast cancer, and may overcome the limitations of current multigene assays.

Effect of healthcare benefits on short-term adherence of positive airway pressure therapy.

PURPOSE: The objective of this study was to assess the impact of healthcare benefits on adherence to positive airway pressure (PAP) therapy in obstructive sleep apnea (OSA) patients. METHODS: Medical records of OSA patients at the Veterans Health Service Medical Center were retrospectively reviewed. OSA patients were assigned to two groups as the date of prescribing PAP: after (=Group A) and before (=Group B) July 1, 2018 when PAP therapy starts to be included in healthcare insurance coverage for OSA patients in South Korea. PAP adherence was compared over a 3-month period between the two groups; subjective improvement after therapy was evaluated using the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index scores. In addition, we evaluated a number of OSA patients who chose to start PAP therapy without healthcare benefit (from July 2018 to December 2018). RESULTS: Each of the 50 patients in the Group A and B exhibited PAP adherence rates of 82% and 26%, respectively (P < .001). Age did not affect PAP adherence in the Group A. The mean apnea-hypopnea index (from 36.7 to 1.34, P < .001) and ESS (from 7.6 to 5.6, P = .004) scores of patients in the Group A had significantly improved within the first three months. Twenty-three (23 out of 334, 6.9%) OSA patients did not have any healthcare insurance, but they medically needed PAP therapy. However, only one of the 23 patients began PAP treatment. CONCLUSION: Short-term PAP adherence significantly improved after PAP therapy was included in healthcare insurance coverage.

Audiologic outcomes and complications of active middle ear implantation in older adults.

BACKGROUND: A few studies have reported the use of middle ear implants (MEIs) in older adults. OBJECTIVES: To evaluate the audiologic outcomes and postoperative complications of MEIs in older adults. METHODS: This retrospective study reviewed audiologic data and medical records from a single referral centre. We identified 34 patients aged ≥65 years who underwent middle ear implantation using the Vibrant SoundbridgeTM device. Preoperative audiometric testing and postoperative aided audiometric testing were performed to evaluate the functional hearing gain at 1 year postoperatively. Patients were divided into 2 groups depending on whether they underwent explantation because of poor hearing benefit. RESULTS: Follow-up duration ranged from <1 to 5.3 years. The functional gain with MEIs significantly improved relative to the preoperative air conduction thresholds at 0.5, 1, 2, and 4 kHz. Eight patients underwent explantation and 7 lost their external audio processor devices. Those who removed their implants because of the poor hearing (group 1) showed significantly worse hearing thresholds at 1 kHz and speech discrimination scores than the others (group 2). CONCLUSIONS AND SIGNIFICANCE: MEIs for auditory rehabilitation can provide improved speech recognition and significant functional gains in older adults. Patients must be given appropriate preoperative explanations regarding the expected outcomes.

TM4SF4 and LRRK2 Are Potential Therapeutic Targets in Lung and Breast Cancers through Outlier Analysis.

PURPOSE: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be 'some sort of problem.' Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). MATERIALS AND METHODS: Modified Tukey's fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. RESULTS: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines. CONCLUSION: Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.