Patient Controlled, Privacy Preserving IoT Healthcare Data Sharing Framework

Healthcare data personally collected by individuals with wearable devices have become important sources of information for healthcare professionals and medical research worldwide. User-Generated Data (UGD) offers unique and sometimes fine-grained insight into the lived experiences and medical conditions of patients. The sensitive subject-matter of medical data can facilitate the exploitation and/or control of victims. Data collection in medical research therefore restricts access control over participant-data to the researchers. Therefore, cultivating trust with prospective participants concerned about the security of their medical data presents formidable challenges. Anonymization can allay such concerns, but at the cost of information loss. Moreover, such techniques cannot necessarily be applied on real-time streaming health data. In this paper, we aim to analyze the technical requirements to enable individuals to share their real-time wearable healthcare data with researchers without compromising privacy. An extension for delay-free anonymization techniques for real-time streaming health data is also proposed

Pharmacologically antagonizing the CXCR4-CXCL12 chemokine pathway with AMD3100 inhibits sunlight-induced skin cancer

One way sunlight causes skin cancer is by suppressing anti-tumor immunity. A major mechanism involves altering mast cell migration via the C-X-C motif chemokine receptor 4–C-X-C motif chemokine ligand 12 (CXCR4-CXCL12) chemokine pathway. We have discovered that pharmacologically blocking this pathway with the CXCR4 antagonist AMD3100 prevents both UV radiation-induced immune suppression and skin cancer. The majority of control mice receiving UV-only developed histopathologically confirmed squamous cell carcinomas. In contrast, skin tumor incidence and burden was significantly lower in AMD3100-treated mice. Perhaps most striking was that AMD3100 completely prevented the outgrowth of latent tumors that occurred once UV irradiation ceased. AMD3100 protection from UV immunosuppression and skin cancer was associated with reduced mast cell infiltration into the skin, draining lymph nodes, and the tumor itself. Thus a major target of CXCR4 antagonism was the mast cell. Our results indicate that interfering with UV-induced CXCL12 by antagonizing CXCR4 significantly inhibits skin tumor development by blocking UV-induced effects on mast cells. Hence, the CXCR4-CXCL12 chemokine pathway is a novel therapeutic target in the prevention of UV-induced skin cancer

Health care cost of crusted scabies in Aboriginal communities in the Northern Territory, Australia.

BACKGROUND: Crusted scabies is a debilitating dermatological condition. Although still relatively rare in the urban areas of Australia, rates of crusted scabies in remote Aboriginal communities in the Northern Territory (NT) are reported to be among the highest in the world. OBJECTIVE: To estimate the health system costs associated with diagnosing, treating and managing crusted scabies. METHODS: A disease pathway model was developed to identify the major phases of managing crusted scabies. In recognition of the higher resource use required to treat more severe cases, the pathway differentiates between crusted scabies severity grades. The disease pathway model was populated with data from a clinical audit of 42 crusted scabies patients diagnosed in the Top-End of Australia's Northern Territory between July 1, 2016 and May 1, 2018. These data were combined with standard Australian unit costs to calculate the expected costs per patient over a 12-month period, as well as the overall population cost for treating crusted scabies. FINDINGS: The expected health care cost per patient diagnosed with crusted scabies is $35,418 Australian dollars (AUD) (95$27,000 to $43,800), resulting in an overall cost of$1,558,392AUD (95% CI: $1,188,000 to$1,927,200) for managing all patients diagnosed in the Northern Territory in a given year (2018). By far, the biggest component of the health care costs falls on the hospital system. DISCUSSION: This is the first cost-of-illness analysis for treating crusted scabies. Such analysis will be of value to policy makers and researchers by informing future evaluations of crusted scabies prevention programs and resource allocation decisions. Further research is needed on the wider costs of crusted scabies including non-financial impacts such as the loss in quality of life as well as the burden of care and loss of well-being for patients, families and communities

Selective Loss of Wild-Type p16INK4a Expression in Human Nevi

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Oncogenic B-RAFV600E Signaling Induces the T-Box3 Transcriptional Repressor to Repress E-Cadherin and Enhance Melanoma Cell Invasion

Approximately 50% of melanomas require oncogenic B-RAFV600E signaling for proliferation, survival, and metastasis, and the use of highly selective B-RAF inhibitors has yielded remarkable, although short-term, clinical responses. Reactivation of signaling downstream of B-RAF is frequently associated with acquired resistance to B-RAF inhibitors, and the identification of B-RAF targets may therefore provide new strategies for managing melanoma. In this report, we applied whole-genome expression analyses to reveal that oncogenic B-RAFV600E regulates genes associated with epithelial–mesenchymal transition in normal cutaneous human melanocytes. Most prominent was the B-RAF-mediated transcriptional repression of E-cadherin, a keratinocyte–melanoma adhesion molecule whose loss is intimately associated with melanoma invasion and metastasis. Here we identify a link between oncogenic B-RAF, the transcriptional repressor Tbx3, and E-cadherin. We show that B-RAFV600E induces the expression of Tbx3, which potently represses E-cadherin expression in melanocytes and melanoma cells. Tbx3 expression is normally restricted to developmental embryonic tissues and promoting cell motility, but it is also aberrantly increased in various cancers and has been linked to tumor cell invasion and metastasis. We propose that this B-RAF/Tbx3/E-cadherin pathway has a critical role in promoting the metastasis of B-RAF-mutant melanomas

Expression of Drug Targets in Patients Treated with Sorafenib, Carboplatin and Paclitaxel

Introduction: Sorafenib, a multitarget kinase inhibitor, targets members of the mitogen-activated protein kinase (MAPK) pathway and VEGFR kinases. Here we assessed the association between expression of sorafenib targets and biomarkers of taxane sensitivity and response to therapy in pre-treatment tumors from patients enrolled in ECOG 2603, a phase III comparing sorafenib, carboplatin and paclitaxel (SCP) to carboplatin, paclitaxel and placebo (CP). Methods: Using a method of automated quantitative analysis (AQUA) of in situ protein expression, we quantified expression of VEGF-R2, VEGF-R1, VEGF-R3, FGF-R1, PDGF-Rβ, c-Kit, B-Raf, C-Raf, MEK1, ERK1/2, STMN1, MAP2, EB1 and Bcl-2 in pretreatment specimens from 263 patients. Results: An association was found between high FGF-R1 and VEGF-R1 and increased progression-free survival (PFS) and overall survival (OS) in our combined cohort (SCP and CP arms). Expression of FGF-R1 and VEGF-R1 was higher in patients who responded to therapy ((CR+PR) vs. (SD+PD+ un-evaluable)). Conclusions: In light of the absence of treatment effect associated with sorafenib, the association found between FGF-R1 and VEGF-R1 expression and OS, PFS and response might reflect a predictive biomarker signature for carboplatin/paclitaxel-based therapy. Seeing that carboplatin and pacitaxel are now widely used for this disease, corroboration in another cohort might enable us to improve the therapeutic ratio of this regimen. © 2013 Jilaveanu et al

KEYNOTE-716: Phase III study of adjuvant pembrolizumab versus placebo in resected high-risk stage II melanoma.

Patients with high-risk stage II melanoma are at significant risk for recurrence after surgical resection. Adjuvant treatment options to lower the risk for distant metastases are limited. Although adjuvant IFN-α2b is associated with improved relapse-free survival in patients with high-risk melanoma, toxicity and limited overall survival benefits limit its use. Adjuvant treatment with the PD-1 inhibitor pembrolizumab significantly improved recurrence-free survival, compared with placebo, in patients with resected stage III melanoma in the Phase III KEYNOTE-054 trial; efficacy in patients with stage II disease has not been established. This article describes the design and rationale of KEYNOTE-716 (NCT03553836), a two-part, randomized, placebo-controlled, multicenter Phase III study of adjuvant pembrolizumab in patients with surgically resected high-risk stage II melanoma. Clinical trial registry & ID: ClinicalTrials.gov, NCT0355383

Melanoma staging: Evidence‐based changes in the American Joint Committee on Cancer eighth edition cancer staging manual

Answer questions and earn CME/CNETo update the melanoma staging system of the American Joint Committee on Cancer (AJCC) a large database was assembled comprising >46,000 patients from 10 centers worldwide with stages I, II, and III melanoma diagnosed since 1998. Based on analyses of this new database, the existing seventh edition AJCC stage IV database, and contemporary clinical trial data, the AJCC Melanoma Expert Panel introduced several important changes to the Tumor, Nodes, Metastasis (TNM) classification and stage grouping criteria. Key changes in the eighth edition AJCC Cancer Staging Manual include: 1) tumor thickness measurements to be recorded to the nearest 0.1 mm, not 0.01 mm; 2) definitions of T1a and T1b are revised (T1a, <0.8 mm without ulceration; T1b, 0.8‐1.0 mm with or without ulceration or <0.8 mm with ulceration), with mitotic rate no longer a T category criterion; 3) pathological (but not clinical) stage IA is revised to include T1b N0 M0 (formerly pathologic stage IB); 4) the N category descriptors “microscopic” and “macroscopic” for regional node metastasis are redefined as “clinically occult” and “clinically apparent”; 5) prognostic stage III groupings are based on N category criteria and T category criteria (ie, primary tumor thickness and ulceration) and increased from 3 to 4 subgroups (stages IIIA‐IIID); 6) definitions of N subcategories are revised, with the presence of microsatellites, satellites, or in‐transit metastases now categorized as N1c, N2c, or N3c based on the number of tumor‐involved regional lymph nodes, if any; 7) descriptors are added to each M1 subcategory designation for lactate dehydrogenase (LDH) level (LDH elevation no longer upstages to M1c); and 8) a new M1d designation is added for central nervous system metastases. This evidence‐based revision of the AJCC melanoma staging system will guide patient treatment, provide better prognostic estimates, and refine stratification of patients entering clinical trials. CA Cancer J Clin 2017;67:472‐492. © 2017 American Cancer Society.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/1/caac21409_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/2/caac21409-sup-0001-suppinfo01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139981/3/caac21409.pd