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Supplemental figure legends. Legends for supplemental figures

Figure S2. Flow of samples

Table S3. Clinical outcomes by PTEN status in patients with BRAF V600 mutations

Purpose: Loss of function of PTEN is a frequent event in melanoma, particularly in tumors with BRAFV600 mutations. The prevalence, pathologic features, and clinical outcomes associated with PTEN loss in patients with stage IIIB/C melanoma were interrogated to improve our understanding of the clinical significance of this molecular event.Experimental Design: Archival tissue from lymphadenectomy specimens among patients (n = 136) with stage IIIB or IIIC melanoma was assessed by DNA sequencing for activating BRAF and NRAS mutations, and by immunohistochemistry for the expression of PTEN protein. Associations of these molecular aberrations with demographics, tumor characteristics, and clinical outcomes were determined.Results: The prevalence of BRAFV600 mutations (40% overall), NRAS mutations (10%), and PTEN loss (25%) did not vary by pathologic substage. BRAF/NRAS mutation status did not correlate with distant disease-free survival (DDFS) or overall survival (OS). Complete loss of PTEN expression correlated with shorter OS but not DDFS. When stratified by specific sites of distant metastasis, PTEN loss was associated with significantly shorter time to melanoma brain metastasis (MBM), but not to liver, lung, or bone metastasis. Analysis of PTEN in mutationally defined subsets showed that PTEN loss was significantly associated with OS and time to MBM in patients with BRAFV600 mutations.Conclusions: Loss of PTEN protein expression correlates significantly with decreased OS and time to MBM in stage IIIB/C melanoma patients with BRAFV600 mutations. The findings add to evidence supporting a significant role for PTEN loss and the PI3K–AKT pathway in melanoma. Clin Cancer Res; 20(21); 5527–36. ©2014 AACR.

Supplementary Figure 1. Representative images of PTEN IHC results in FFPE melanoma tissue samples.

To explore the experiences of a nursing team who implemented an international nurse-led clinical trial in practice and understand the facilitators to their involvement.The role and responsibilities of the clinical nurse are advancing to encompass research activity to help inform evidence-based practice. However, several personal and organisational challenges can inhibit nurses' capacity to implement and undertake research within clinical practice.Three focus groups were conducted with members of a nursing team (N = 18). Thematic analysis was employed, and themes were identified and agreed upon by the research team.Five themes were identified: 'Previous experience of and attitudes to participation in clinical research', 'Decision-making regarding participation in the clinical trial', 'Facilitators of participation in the clinical trial', 'Challenges of research in nursing practice' and 'Future orientation towards research'.Through their experiences of implementing a nurse-led clinical trial within practice, nurses recognized a number of facilitators and challenges to their participation. The perceived relevance of the clinical trial to the nurses' practice, potential to improve patient care and appreciation of the nurse leader's expertise and understanding of their context were key motivators. Reciprocal trust with the nurse leader who was encouraging, motivating, supportive and accessible resulted in the engagement and commitment of the nursing team.This paper offers a perspective that can inform senior nursing management teams when implementing and conducting evidence-based research amongst nursing teams and in doing so meet the needs of developing research capacity amongst clinical nurses.

Clinically significant fungal infections of the upper extremity are uncommon but increasing They are classified based on anatomic location and epidemiology. The anatomic categories that affect the hand include cutaneous, subcutaneous, and deep. Cutaneous infections are caused by organisms that metabolize keratin and can cause serious morbidity but are rarely fatal. Subcutaneous infections are similar to the cutaneous infections and are produced by low virulence organisms. Cutaneous and subcutaneous infections are most common and can be treated by primary care physicians and dermatologists. Deep infections are less common but can be fatal. Epidemiologic classifications include endemic and opportunistic infections.

Smoking among cancer patients leads to poorer outcomes, yet many patients continue smoking. As part of a feasibility study of smoking cessation for cancer patients in Ireland, smoking rates were reviewed. Hospital Inpatient Enquiry (HIPE) data on the smoking status of discharges with a cancer diagnosis (overall, breast, lung, cervical and head and neck cancer) were used (2014–2018). During 2014–2017, current smoking increased for overall (10.5–11.7%) and lung cancer (24.7–27.2%), then decreased to 11.4% and 24.1%, respectively, in 2018. Current smoking increased for cervical during 2014–2018 (11–19.8%) and initially (2014–2016) for head and neck (3–12.7%) cancer, decreasing to 7.6% in 2018; breast cancer was stable at 6 ± 0.6%. These rates are lower than the Irish (23–20%) and European (29% (average)) general population. During 2014–2017, past smoking increased among overall (15.2–21%) and specific cancers, which was lower than the Irish general population (23–28%). Current smoking was highest among 50–59-year-olds (14–16%), which contrasts with the Irish general population (24–35 years at 32–28%). HIPE data are subject to potential duplicate episodes of care and under-documentation of smoking. However, trend analysis is useful, as these limitations should be stable. Rates remain high; therefore, robust documentation and smoking cessation referrals for cancer patients are important.

The detrimental impact of smoking on health and wellbeing are irrefutable. Additionally, smoking is associated with the development of cancer, a reduction treatment outcomes and poorer health outcomes. Nevertheless, a significant number of people continue to smoke following a cancer diagnosis. Little is understood of the smoking cessation services provided to smokers with cancer or their engagement with them. This systematic review aimed to identify existing smoking cessation interventions for this cohort diagnosed with breast, head and neck, lung and cervical cancers (linked to risk). Systematic searches of Pubmed, Embase, Psych Info and CINAHL from 1 January 2015 to 15 December 2020 were conducted. Included studies examined the characteristics of smoking cessation interventions and impact on referrals and quit attempts. The impact on healthcare professionals was included if reported. Included studies were restricted to adults with a cancer diagnosis and published in English. No restriction was placed on study designs, and narrative data synthesis was conducted due to heterogeneity. A review protocol was registered on PROSPERO CRD 42020214204, and reporting adheres to PRISMA reporting guidelines. Data were screened, extracted in duplicate and an assessment of the quality of evidence undertaken using Mixed Methods Assessment Tool. 23 studies met the inclusion criteria, representing USA, Canada, England, Lebanon, Australia and including randomized controlled trials (9), observational studies (10), quality improvement (3), and one qualitative study. Hospital and cancer clinics [including a dental clinic] were the settings for all studies. 43% (10/23) of studies reported interventions for smokers diagnosed with head and neck cancer, 13% (3/23) for smokers diagnosed with lung cancer, one study provides evidence for breast cancer, and the remaining nine studies (39%) report on multiple cancers including the ones specified in this review. Methodological quality was variable. There were limited data to identify one optimal intervention for this cohort. Key elements included the timing and frequency of quit conversations, use of electronic records, pharmacotherapy including extended use of varenicline, increased counselling sessions and a service embedded in oncology departments. More studies are required to ensure tailored smoking cessation pathways are co-developed for smokers with a diagnosis of cancer to support this population.

Introduction The clinical-histologic correlation in diabetic nephropathy is not completely known. Methods We analyzed nephrectomy specimens from 90 patients with diabetes and diverse degrees of proteinuria and glomerular filtration rate (GFR). Results Thirty-six (40%) subjects had normoalbuminuria, 33 (37%) microalbuminuria, and 21 (23%) non-nephrotic proteinuria. Mean estimated GFR (eGFR) was 65±23 (40% 10% to 20% of the sample. Moderate hyalinosis and arteriolar sclerosis were observed in 80% to 100% of cases with normoalbuminuria, microalbuminuria, proteinuria, as well as in class I, II, or III. Conclusions Weak correspondence between analytical parameters and kidney histology was found. Thus, disease may progress undetected from the early clinical stages of the disease. Finally, vascular damage was a very common finding, which highlights the role of ischemic intrarenal disease in diabetes., Graphical abstract

The study presented here is the first empirical investigation of attitudes towards Multicultural London English (MLE), the multiethnolect spoken in England’s main metropolis. An online ques...

Objective To evaluate effects of remote monitoring of adjuvant chemotherapy related side effects via the Advanced Symptom Management System (ASyMS) on symptom burden, quality of life, supportive care needs, anxiety, self-efficacy, and work limitations. Design Multicentre, repeated measures, parallel group, evaluator masked, stratified randomised controlled trial. Setting Twelve cancer centres in Austria, Greece, Norway, Republic of Ireland, and UK. Participants 829 patients with non-metastatic breast cancer, colorectal cancer, Hodgkin’s disease, or non-Hodgkin’s lymphoma receiving first line adjuvant chemotherapy or chemotherapy for the first time in five years. Intervention Patients were randomised to ASyMS (intervention; n=415) or standard care (control; n=414) over six cycles of chemotherapy. Main outcome measures The primary outcome was symptom burden (Memorial Symptom Assessment Scale; MSAS). Secondary outcomes were health related quality of life (Functional Assessment of Cancer Therapy—General; FACT-G), Supportive Care Needs Survey Short-Form (SCNS-SF34), State-Trait Anxiety Inventory—Revised (STAI-R), Communication and Attitudinal Self-Efficacy scale for cancer (CASE-Cancer), and work limitations questionnaire (WLQ). Results For the intervention group, symptom burden remained at pre-chemotherapy treatment levels, whereas controls reported an increase from cycle 1 onwards (least squares absolute mean difference −0.15, 95% confidence interval −0.19 to −0.12; P Conclusions Significant reduction in symptom burden supports the use of ASyMS for remote symptom monitoring in cancer care. A “medium” Cohen’s effect size of 0.5 showed a sizable, positive clinical effect of ASyMS on patients’ symptom experiences. Remote monitoring systems will be vital for future services, particularly with blended models of care delivery arising from the covid-19 pandemic. Trial registration Clinicaltrials.gov NCT02356081 .

The effects of chemotherapy dose intensity on patient outcomes in advanced cancer are not well understood. We studied the association between chemotherapy relative dose intensity (RDI) and overall survival (OS) among patients with advanced breast or ovarian cancer.This retrospective cohort study included adults with advanced breast or ovarian cancer who received first-line myelosuppressive chemotherapy (January 2007 to December 2010) in US Oncology Network community practices. Dose delays ≥ 7 days, dose reductions ≥ 15%, and RDI relative to standard regimens were described. OS was measured by the Kaplan-Meier method and Cox proportional hazards models.Among 874 patients with advanced breast cancer, 33.2% experienced dose delays ≥ 7 days, 48.7% experienced dose reductions ≥ 15%, and 38.9% had RDI 85%. In the multivariable Cox proportional hazards model, Eastern Cooperative Oncology Group performance status 1/2 versus 0 (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.15-1.82) and triple-negative status (HR = 3.14; 95% CI, 1.15-8.62) were significantly associated with mortality. Among 170 patients with advanced ovarian cancer, 43.5% experienced dose delays ≥ 7 days, 48.2% experienced dose reductions ≥ 15%, and 46.5% had RDI 85%. In the multivariable Cox proportional hazards model, dose reductions ≥ 15% (HR = 1.94; 95% CI, 1.09-3.46) and other tumor histology (vs. nonserous adenocarcinoma; HR = 3.55; 95% CI, 1.38-9.09) were significantly associated with mortality.Dose delays, dose reductions, and reduced RDI were common. In advanced breast cancer, health status and triple-negative disease were significantly associated with mortality. In advanced ovarian cancer, dose reductions and tumor histology were significantly associated with mortality. These results can help identify potential risk factors and characterize the effect of chemotherapy dose modification strategies on mortality.