IntroductionTriple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients.MethodsWe conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n = 87) was used for validation.ResultsFuzzy clustering separated triple-negative tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P < 0.0001 for both comparisons). Significant event-free survival (P = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 (P = 0.01) and C2 (P = 0.02). Event-free survival analysis results were confirmed when our cohort was pooled with the external cohort (n = 194; P = 0.01). Functional annotation showed that 22% of triple-negative patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response and low M2-like macrophages were a hallmark of C3, and that these patients had a better event-free survival than C2 patients, characterized by low immune response and high M2-like macrophages: P = 0.02 for our cohort, and P = 0.03 for pooled cohorts.ConclusionsWe identified three subtypes of triple-negative patients: luminal androgen receptor (22%), basal-like with low immune response and high M2-like macrophages (45%), and basal-enriched with high immune response and low M2-like macrophages (33%). We noted out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in triple-negative basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype triple-negative patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0550-y) contains supplementary material, which is available to authorized users.

MCI is highly prevalent in older adults with profound hearing loss. Nevertheless, we observed a low rate of progression to dementia, and cognitive function improved in some individuals with MCI at baseline. These results highlight that cochlear implantation should be strongly considered in profoundly deaf individuals, even those with MCI, who may have a specific subtype of MCI, with a possible positive effect of hearing rehabilitation on neurocognitive functioning.

Purpose The extant response shift definitions and theoretical response shift models, while helpful, also introduce predicaments and theoretical debates continue. To address these predicaments and stimulate empirical research, we propose a more specific formal definition of response shift and a revised theoretical model. Methods This work is an international collaborative effort and involved a critical assessment of the literature. Results Three main predicaments were identified. First, the formal definitions of response shift need further specification and clarification. Second, previous models were focused on explaining change in the construct intended to be measured rather than explaining the construct at multiple time points and neglected the importance of using at least two time points to investigate response shift. Third, extant models do not explicitly distinguish the measure from the construct. Here we define response shift as an effect occurring whenever observed change (e.g., change in patient-reported outcome measures (PROM) scores) is not fully explained by target change (i.e., change in the construct intended to be measured). The revised model distinguishes the measure (e.g., PROM) from the underlying target construct (e.g., quality of life) at two time points. The major plausible paths are delineated, and the underlying assumptions of this model are explicated. Conclusion It is our hope that this refined definition and model are useful in the further development of response shift theory. The model with its explicit list of assumptions and hypothesized relationships lends itself for critical, empirical examination. Future studies are needed to empirically test the assumptions and hypothesized relationships.

Objective To assess through multivariate analysis the clinical pre- and intraoperative factors of facial nerve outcomes at day 8 and 1-year recovery of facial palsy, as compared with day 8 status among patients who underwent total resection of unilateral vestibular schwannoma. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods This study included 229 patients with preoperative normal facial function and anatomic preservation of the facial nerve. Clinical, radiologic, and intraoperative factors were assessed according to facial nerve function at day 8 and 1 year. Results We observed that 74% and 84% of patients had good facial function (House-Brackmann [HB] I-II) at day 8 and 1 year, respectively. Of 60 patients, 26 (43%) who had impaired facial function (HB III-VI) at day 8 recovered good facial function (HB I-II) 1 year after surgery. A structured equation model showed that advanced tumor stage and strong facial nerve adhesion were independently associated with facial nerve conduction block at day 8. No predictive factor of impaired facial function recovery was seen at 1 year. In terms of the extracanalicular diameter of the tumor, the cutoff point to minimize the risk of impaired facial function was 16 mm. Conclusion At day 8 after vestibular schwannoma resection, facial function was impaired in the case of large tumors or strong facial nerve adhesion to the tumor. After 1 year, less than half of the patients recovered good facial function, and no predictive factor was found to be associated with this possible recovery.

A correction to this paper has been published: https://doi.org/10.1007/s11136-021-02890-6

NCT01648907.

Background: Using a real dataset, we highlighted several major methodological issues raised by the estimation of the Minimal Clinically Important Difference (MCID) of a Patient-Reported Outcomes instrument. We especially considered the management of missing data and the use of more than two times of measurement. While inappropriate missing data management and inappropriate use of multiple time points can lead to loss of precision and/or bias in MCID estimation, these issues are almost never dealt with and require cautious considerations in the context of MCID estimation. Methods: We used the LIGALONGO study (French Randomized Controlled Trial). We estimated MCID on the SF-36 General Health score by comparing many methods (distribution or anchor-based). Different techniques for imputation of missing data were performed (simple and multiple imputations). We also consider all measurement occasions by longitudinal modeling, and the dependence of the score difference on baseline. Results: Three hundred ninety-three patients were studied. With distribution-based methods, a great variability in MCID was observed (from 3 to 26 points for improvement). Only 0.2 SD and 1/3 SD distribution methods gave MCID values consistent with anchor-based methods (from 4 to 7 points for improvement). The choice of missing data imputation technique clearly had an impact on MCID estimates. Simple imputation by mean score seemed to lead to out-of-range estimate, but as missing not at random mechanism can be hypothesized, even multiple imputations techniques can have led to an slight underestimation of MCID. Using 3 measurement occasions for improvement led to an increase in precision but lowered estimates. Conclusion: This practical example illustrates the substantial impact of some methodological issues that are usually never dealt with for MCID estimation. Simulation studies are needed to investigate those issues. Trial registration: NCT01240772 (ClinicalTrials.gov) registered on November 15, 2010.

OBJECTIVE In large vestibular schwannoma (VS) surgery, the facial nerve (FN) is at high risk of injury. Near-total resection has been advocated in the case of difficult facial nerve dissection, but the amount of residual tumor that should be left and when dissection should be stopped remain controversial factors. The objective of this study was to report FN outcome and radiological results in patients undergoing near-total VS resection guided by electromyographic supramaximal stimulation of the FN at the brainstem. METHODS This study was a retrospective analysis of a prospectively maintained database. Inclusion criteria were surgical treatment of a large VS during 2014, normal preoperative FN function, and an incomplete resection due to the strong adherence of the tumor to the FN and the loss of around 50% of the response of supramaximal stimulation of the proximal FN at 2 mA. Facial nerve function and the amount and evolution of the residual tumor were evaluated by clinical examination and by MRI at a mean of 5 days postoperatively and at 1 year postoperatively. RESULTS Twenty-five patients met the inclusion criteria and were included in the study. Good FN function (Grade I or II) was observed in 16 (64%) and 21 (84%) of the 25 patients at Day 8 and at 1 year postoperatively, respectively. At the 1-year follow-up evaluation (n = 23), 15 patients (65%) did not show growth of the residual tumor, 6 patients (26%) had regression of the residual tumor, and only 2 patients (9%) presented with tumor progression. CONCLUSIONS Near-total resection guided by electrophysiology represents a safe option in cases of difficult dissection of the facial nerve from the tumor. This seems to offer a good compromise between the goals of preserving facial nerve function and achieving maximum safe resection.