Radiomics analysis has emerged as a promising approach for extracting quantitative features from medical images to aid in cancer diagnosis and treatment. However, radiomics research currently lacks ...standardization, and radiomics features can be highly dependent on the acquisition and pre-processing techniques used. In this study, we aim to investigate the effect of various intensity normalization techniques on the robustness of radiomics features extracted from MRI scans of breast cancer patients. The images used are from the publicly available I-SPY TRIAL dataset, which contains MRI scans of stage 2 or 3 breast cancer patients and from the Platinum and PARP inhibitor for Neoadjuvant treatment of Triple Negative and / or BRCA positive breast cancer (PARTNER) trial. We compared the effect of commonly used intensity normalization techniques on the robustness of radiomics features using Intraclass Correlation Coefficient (ICC) between multiple combinations of normalization approaches, identified categories that are robust and therefore could be compared between studies regardless of the pre-processing used. We were able to show that while systematic differences between MRI scanners can significantly affect many radiomics features, a combination of Bias Field correction with piecewise linear histogram normalization can mitigate some of the effects compared to other normalization methods investigated in this paper. We were able to demonstrate the importance of carefully selecting and standardizing normalization methods for accurate and reliable radiomics analysis in breast MRI scans.
Summary Background Patients with progressive disease after two or more HER2-directed regimens for recurrent or metastatic breast cancer have few effective therapeutic options. We aimed to compare ...trastuzumab emtansine, an antibody–drug conjugate comprising the cytotoxic agent DM1 linked to trastuzumab, with treatment of physician's choice in this population of patients. Methods This randomised, open-label, phase 3 trial took place in medical centres in 22 countries across Europe, North America, South America, and Asia-Pacific. Eligible patients (≥18 years, left ventricular ejection fraction ≥50%, Eastern Cooperative Oncology Group performance status 0–2) with progressive HER2-positive advanced breast cancer who had received two or more HER2-directed regimens in the advanced setting, including trastuzumab and lapatinib, and previous taxane therapy in any setting, were randomly assigned (in a 2:1 ratio) to trastuzumab emtansine (3·6 mg/kg intravenously every 21 days) or physician's choice using a permuted block randomisation scheme by an interactive voice and web response system. Patients were stratified according to world region (USA vs western Europe vs other), number of previous regimens (excluding single-agent hormonal therapy) for the treatment of advanced disease (two to three vs more than three), and presence of visceral disease (any vs none). Coprimary endpoints were investigator-assessed progression-free survival (PFS) and overall survival in the intention-to-treat population. We report the final PFS analysis and the first interim overall survival analysis. This study is registered with ClinicalTrials.gov , number NCT01419197. Findings From Sept 14, 2011, to Nov 19, 2012, 602 patients were randomly assigned (404 to trastuzumab emtansine and 198 to physician's choice). At data cutoff (Feb 11, 2013), 44 patients assigned to physician's choice had crossed over to trastuzumab emtansine. After a median follow-up of 7·2 months (IQR 5·0–10·1 months) in the trastuzumab emtansine group and 6·5 months (IQR 4·1–9·7) in the physician's choice group, 219 (54%) patients in the trastuzumab emtansine group and 129 (65%) of patients in the physician's choice group had PFS events. PFS was significantly improved with trastuzumab emtansine compared with physician's choice (median 6·2 months 95% CI 5·59–6·87 vs 3·3 months 2·89–4·14; stratified hazard ratio HR 0·528 0·422–0·661; p<0·0001). Interim overall survival analysis showed a trend favouring trastuzumab emtansine (stratified HR 0·552 95% CI 0·369–0·826; p=0·0034), but the stopping boundary was not crossed. A lower incidence of grade 3 or worse adverse events was reported with trastuzumab emtansine than with physician's choice (130 events 32% in 403 patients vs 80 events 43% in 184 patients). Neutropenia (ten 2% vs 29 16%), diarrhoea (three <1% vs eight 4%), and febrile neutropenia (one <1% vs seven 4%) were grade 3 or worse adverse events that were more common in the physician's choice group than in the trastuzumab emtansine group. Thrombocytopenia (19 5% vs three 2%) was the grade 3 or worse adverse event that was more common in the trastuzumab emtansine group. 74 (18%) patients in the trastuzumab emtansine group and 38 (21%) in the physician's choice group reported a serious adverse event. Interpretation Trastuzumab emtansine should be considered as a new standard for patients with HER2-positive advanced breast cancer who have previously received trastuzumab and lapatinib. Funding Genentech.
Innovations in mobile and electronic healthcare are revolutionizing the involvement of both doctors and patients in the modern healthcare system by extending the capabilities of physiological ...monitoring devices. Despite significant progress within the monitoring device industry, the widespread integration of this technology into medical practice remains limited. The purpose of this review is to summarize the developments and clinical utility of smart wearable body sensors.
We reviewed the literature for connected device, sensor, trackers, telemonitoring, wireless technology and real time home tracking devices and their application for clinicians.
Smart wearable sensors are effective and reliable for preventative methods in many different facets of medicine such as, cardiopulmonary, vascular, endocrine, neurological function and rehabilitation medicine. These sensors have also been shown to be accurate and useful for perioperative monitoring and rehabilitation medicine.
Although these devices have been shown to be accurate and have clinical utility, they continue to be underutilized in the healthcare industry. Incorporating smart wearable sensors into routine care of patients could augment physician-patient relationships, increase the autonomy and involvement of patients in regards to their healthcare and will provide for novel remote monitoring techniques which will revolutionize healthcare management and spending.
Highlights • Lactate & SCFAs regulate proinflammatory activation of epithelial and myeloid cells. • Butyrate/propionate are effective at lower concentrations than lactate/acetate. • Lactate & SCFAs ...are immunomodulatory at intestinal physiological concentrations. • Modulatory activity of SCFAs and lactate are not related to Gi signaling. • These molecules could be useful in gastrointestinal inflammatory situations.
To determine the prevalence of cognitive complaints and HIV-associated neurocognitive disorders (HANDs) in a cohort of aviremic HIV-positive patients. To evaluate the relevance of the HIV dementia ...scale to detect HANDs.
Assessment of HANDs with neuropsychological tests.
Two hundred HIV-infected patients with undetectable HIV-1 RNA concentrations in the plasma, no history of major opportunistic infection of the central nervous system in the past 3 years, no current use of intravenous drugs, and no major depression answered a questionnaire designed to elicit cognitive complaints. Cognitive functions of 50 complaining and 50 noncomplaining HIV-positive patients were assessed.
Patients had undetectable HIV-1 RNA concentrations for a median time of 48 months (range 3.2-136.6). The prevalence of cognitive complaints was 27%. The prevalence of HANDs was 84% among patients with cognitive complaints (asymptomatic neurocognitive impairment 24%, mild neurocognitive disorders 52%, and HIV-associated dementia 8%) and 64% among noncomplainers (asymptomatic neurocognitive impairment 60%, mild neurocognitive disorders 4%, and HIV-associated dementia 0%; P < 0.001). A score of 14 points or less on the HIV dementia scale yielded a positive predictive value of HANDs of 92% in complainers and 82% in noncomplainers.
The prevalence of HANDs is high even in long-standing aviremic HIV-positive patients. However, HANDs without functional repercussion in daily life (asymptomatic neurocognitive impairment) is the most frequent subtype observed. In this population, the HIV dementia scale with a cutoff of 14 points or less seems to provide a useful tool to screen for the presence of HANDs.
The cytochrome c oxidase subunit III (COIII) transcript of T. brucei is extensively edited by the addition and deletion of uridines. We have identified partially edited COIII RNAs; they have unedited ...5' and edited 3' regions. Transcripts with edited 5' but unedited 3' regions were not detected. The partially edited RNAs may be editing intermediates. The junctions of unedited and edited sequences in cDNAs differ from both the DNA and fully edited mRNA sequences over a multinucleotide region. The partially edited RNAs could arise from several processes, but it seems likely that editing proceeds in the 3' to 5' direction.
The objective of this study is to ascertain the effects of the left (LV) and right (RV) ventricular lead tip position in response to cardiac resynchronization therapy (CRT).
The REVERSE randomized ...trial examined the effects of CRT in patients with asymptomatic or mildly symptomatic heart failure (HF).
We analysed data collected from the active group (CRT-ON) of REVERSE in whom the precise locations of the LV and RV ventricular lead tips were determined from postoperative chest roentgenograms as part of a prespecified sub-study. LV position was classified as lateral or non-lateral, and apical or non-apical. RV position was classified as apical or non-apical. Echocardiographic LV end-systolic volume index (LVESVi), QRS duration, and clinical outcomes at 12-24 months of follow-up were evaluated with respect to the lead tip position. The primary trial endpoint was the proportion of patients with a worsened HF clinical composite response, scored as improved, unchanged, or worsened.
Totally 346 patients included in this analysis were followed for a median of 12.6 months (interquartile range: 11.9-23.9 months). The proportion of worsened HF clinical composite response did not correlate with lead position, whereas a significantly greater decrease in the powered secondary endpoint of LVESVi was observed with the non-apical vs. the apical LV lead positions. CRT-paced QRS duration was significantly shorter than at baseline in patients with lateral vs. non-lateral LV position, as well non-apical vs. apical LV position. The incidence of composite endpoint of death and first hospitalization for HF was lower in the LV lateral than in the non-lateral (HR 0.44; 95% CI 0.19-0.99; P= 0.04), and in the LV non-apical than in the apical group (HR 0.27; 95% CI 0.11-0.63; P= 0.001). No significant differences were observed between RV apical and non-apical positions of the lead tip.
A more favourable outcome of CRT with regard to LV reverse remodelling and the composite of time to death or first HF hospitalization was observed when the LV lead tip was implanted in the lateral wall, away from the apex, while the position of the RV lead tip was indifferent. The long-term change in QRS duration was significantly associated with the position of the LV lead tip. ClinicalTrials.gov Identifier: NCT00271154.
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