bluuebunny/crossref_metadata_2025 huggingface dataset:
Out-of-Pocket Costs and Perceived Financial Burden Associated with Prostate Cancer Treatment in a Quebec Remote Area: A Cross-Sectional Study
Authors: El-Haouly Abir , Lacasse Anais , El-Rami Hares , Liandier Frederic , Dragomir Alice
Published: January 2021

Background: In publicly funded healthcare systems, patients do not pay for medical visits but can experience costs stemming from travel or over-the-counter drugs. We lack information about the extent of this burden in Canadian remote regions. This study aimed to: (1) describe prostate cancer-related out-of-pocket costs and perceived financial burden, and (2) identify factors associated with such a perceived burden among prostate cancer patients living in a remote region of the province of Quebec (Canada). Methods: A cross-sectional study was conducted among 171 prostate cancer patients who consulted at the outpatient clinic of the Centre Hospitalier de Rouyn-Noranda. Results: The majority of patients (83%) had incurred out-of-pocket costs for their cancer care. The mean total cost incurred in the last three months was $517 and 22.3% reported a moderate, considerable or unsustainable burden. Multivariable analysis revealed that having incurred higher cancer-related out-of-pocket costs (OR: 1.001; 95%CI: 1.001–1.002) private drug insurance (vs. public, OR: 5.23; 95%CI: 1.13–24.17) was associated with a greater perceived financial burden. Having better physical health-related quality of life (OR: 0.95; 95%CI: 0.913–0.997), a university education (vs. elementary/high school level, OR: 0.03; 95%CI: 0.00–0.79), and an income between $40,000 and $79,999 (vs. ≤ $39,999, OR: 0.15; 95%CI: 0.03–0.69) were associated with a lower perceived burden. Conclusion: Prostate cancer patients incur out-of-pocket costs even if they were diagnosed many years ago and the perceived burden is significant. Greater attention should be paid to the development of services to help patients manage this burden.
Oncolytic Viruses and Hematological Malignancies: A New Class of Immunotherapy Drugs
Authors: Innao Vanessa , Rizzo Vincenzo , Allegra Andrea Gaetano , Musolino Caterina , Allegra Alessandro
Published: January 2021

The use of viruses for tumour treatment has been imagined more than one hundred years ago, when it was reported that viral diseases were occasionally leading to a decrease in neoplastic lesions. Oncolytic viruses (OVs) seem to have a specific tropism for tumour cells. Previously, it was hypothesised that OVs’ antineoplastic actions were mainly due to their ability to contaminate, proliferate and destroy tumour cells and the immediate destructive effect on cells was believed to be the single mechanism of action of OVs’ action. Instead, it has been established that oncolytic viruses operate via a multiplicity of systems, including mutation of tumour milieu and a composite change of the activity of immune effectors. Oncolytic viruses redesign the tumour environment towards an antitumour milieu. The aim of our work is to evaluate the findings present in the literature about the use of OVs in the cure of haematological neoplastic pathologies such as multiple myeloma, acute and chronic myeloid leukaemia, and lymphoproliferative diseases. Further experimentations are essential to recognize the most efficient virus or treatment combinations for specific haematological diseases, and the combinations able to induce the strongest immune response.
A Randomized Controlled Trial Comparing Alloderm-RTU with DermACELL in Immediate Subpectoral Implant-Based Breast Reconstruction
Authors: Arnaout Angel , Zhang Jing , Frank Simon , Momtazi Moein , Cordeiro Erin , Roberts Amanda , Ghumman Ammara , Fergusson Dean , Stober Carol , Pond Gregory , Jeong Ahwon , Vandermeer Lisa , Hutton Brian , Clemons Mark ,   on behalf of the REaCT Investigators
Published: January 2021

Background: The effectiveness of different acellular dermal matrices (ADM) used for implant-based reconstruction immediately following mastectomy is an important clinical question. A prospective randomized clinical trial was performed to evaluate the superiority of DermACELL over Alloderm-RTU in reducing drain duration. Methods: Patients undergoing mastectomy with subpectoral immediate and permanent implant-based breast reconstruction were randomized to Alloderm-RTU or DermACELL. The primary outcome was seroma formation, measured by the duration of postoperative drain placement. Secondary outcomes included: post drain removal seroma aspiration, infection, redbreast syndrome, wound dehiscence, loss of the implant, and unplanned return to the operating room. Results: 62 patients were randomized for 81 mastectomies (41 Alloderm-RTU, 40 DermACELL). Baseline characteristics were similar. There was no statistically significant difference in mean drain duration (p = 0.16), with a trend towards longer duration in the Alloderm-RTU group (1.6 days; 95%CI, 0.7 to 3.9). The overall rate of minor and major complications were statistically similar between the two groups; although patients with Alloderm-RTU had 3 times as many infections requiring antibiotics (7.9% vs. 2.5%) with a risk difference of 5.4 (95%CI −4.5 to 15.2), and twice as many unplanned returns to the operating room (15.8% vs. 7.5%) with a risk difference of 8.3 (95% CI −5.9 to 22.5) as DermACELL. Conclusion: This is the first prospective randomized clinical trial comparing the two most commonly used human-derived ADMs. There was no statistically significant difference in drain duration, minor, or major complications between DermACELL over Alloderm-RTU in immediate subpectoral permanent implant-based breast reconstruction post-mastectomy.
A Rare p.T599dup BRAF Mutant NSCLC in a Non-Smoker
Authors: Turshudzhyan Alla , Vredenburgh James
Published: January 2021

V-RAF murine sarcoma viral oncogene homolog B1 (BRAF) mutated non-small-cell lung cancer (NSCLC) is an exceptionally rare form of lung cancer, found only in one to two percent of patients with an NSCLC diagnosis. BRAF NSCLC traditionally affects former or active smokers. BRAF mutations have always been of special interest to the oncological community, as they offer potential for targeted therapies. BRAF mutation spectrum includes mutations that are of both V600 and non-V600 types. BRAF V600 is an activating mutation, which results in high kinase activity and overproduction of active oncoproteins such as rapidly accelerated fibrosarcoma (RAF). This makes them susceptible to targeted therapies with RAF inhibitors. There has been little evidence, however, regarding efficacy of RAF inhibitors towards non-activating mutations that have intermediate to low kinase activity, such as non-V600 BRAF mutations. While several approaches have been investigated to overcome the limitations of RAF inhibitors, such as use of mitogen-activated protein kinase kinase (MEK) and extracellular signal-regulated kinase (ERK) inhibitors or combination of MEK and RAF inhibitors, none of them have been proven to have a superior efficacy for low kinase activity non-V600 BRAF tumors. We present a case of an extremely rare variant of NSCLC BRAF p.T599dup mutation in a non-smoker that responded to a targeted combination therapy with RAF and MEK inhibitors. The patient responded well to therapy that usually targets high kinase activity V600 mutations. Our hope is to bring more attention to non-V600 mutations and document their responses to existing and new therapies.
Tuberculous Lymphadenitis in a Patient Receiving PD-1 Inhibitor for Melanoma: A Case Report and Brief Literature Review
Authors: Akagunduz Baran , Ozer Muhammet , Bozkina Ali Cagatay , Lebe Banu
Published: January 2021

Oncolytic immunotherapy is a novel and promising approach in clinical oncology practice. Currently, immune checkpoint inhibitors (ICIs) are the first-line treatment options for disseminated melanoma. Nivolumab is a well-defined ICI that blocks programmed cell death 1 (PD-1) and mainly increases anti-tumor immunity. The opportunistic infections are not expected with ICI therapies due to their immune reactivation effects. To date, only a few cancer patients have been reported with activated TB during ICI therapy. Here, we presented a young female patient diagnosed with histologically-confirmed tuberculous lymphadenitis while on nivolumab therapy for metastatic melanoma. The current case report represents the first described tuberculous lymphadenitis case related to anti-PD-1 based monoclonal antibody therapy. The mechanism underlying the development of TB with PD-1 inhibitor use has not been illuminated yet. Triggering of excessive inflammatory responses with ICIs therapy is a potential cause. Considering the increased utilization of ICI-based immunotherapies, the TB screening should be considered in all patients before starting PD-1 inhibitor therapy.
Impact of Oral Targeted Therapy on the Economic Burden of Chronic Lymphocytic Leukemia in Canada
Authors: Lachaine Jean , Beauchemin Catherine , Guinan Kimberly , Thebault Philippe , Aw Andrew , Banerji Versha , Fleury Isabelle , Owen Carolyn
Published: January 2021

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden.
Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Pediatric Patients
Authors: Perreault Sébastien , Chami Rose , Deyell Rebecca J. , El Demellawy Dina , Ellezam Benjamin , Jabado Nada , Morgenstern Daniel A. , Narendran Aru , Sorensen Poul H. B. , Wasserman Jonathan D. , Yip Stephen
Published: January 2021

Neurotrophic tyrosine receptor kinase gene fusions (NTRK) are oncogenic drivers present at a low frequency in most tumour types (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., infantile fibrosarcoma [IFS]) and considered mutually exclusive with other common oncogenic drivers. Health Canada recently approved two tyrosine receptor kinase (TRK) inhibitors, larotrectinib (for adults and children) and entrectinib (for adults), for the treatment of solid tumours harbouring NTRK gene fusions. In Phase I/II trials, these TRK inhibitors have demonstrated promising overall response rates and tolerability in patients with TRK fusion cancer who have exhausted other treatment options. In these studies, children appear to have similar responses and tolerability to adults. In this report, we provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor for pediatric patients with solid tumours. We focus on three pediatric tumour types: non-rhabdomyosarcoma soft tissue sarcoma/unspecified spindle cell tumours including IFS, differentiated thyroid carcinoma, and glioma. We also propose a tumour-agnostic consensus based on the probability of the tumour harbouring an NTRK gene fusion. For children with locally advanced or metastatic TRK fusion cancer who have either failed upfront therapy or lack satisfactory treatment options, TRK inhibitor therapy should be considered.
Utilization and Complications of Central Venous Access Devices in Oncology Patients
Authors: Akhtar Narmeen , Lee Linda
Published: January 2021

Purpose: To describe how central venous access devices (CVADs) are utilized for ambulatory oncology patients and to evaluate the rate of complications. Method: Single institution retrospective study of oncology patients with CVADs who received systemic treatment at the Walker Family Cancer Centre (WFCC) between 1 January and 31 December 2018. Results: A total of 480 CVADS were placed in 305 patients, of which 408 (85%) were peripherally inserted central catheters (PICCs) and 72 (15%) were implanted vascular access devices (PORTs). The incidence of early and late complications was 9% and 24%, respectively. For the entire cohort, the rate of venous thromboembolism (VTE) was 16%, of which 9% were CVAD-related thrombosis (CRTs) and 7% were distant VTE. The CRT rates were similar for PICCs and PORTs (9% vs. 7%). A total of 6% of CVADs were complicated by infection (i.e., localized infections and bacteremia), with a total infection rate of 0.43 and 0.26 per 1000 indwelling days for PICCs and PORTs, respectively. The incidence of central line associated bloodstream infections (CLABSI) was greater for PICCs than PORTs, at a rate of 0.22 compared with 0.08 per 1000 indwelling days, respectively. The premature catheter removal rate was 26% for PICCs and 18% for PORTs. PORTs required more additional hospital visits. Conclusions: PICCs were utilized more frequently than PORTs and had a higher rate of premature removal. The rates of VTE and CRT were similar for both CVAD types. PORTs had a lower rate of infection per 1000 indwelling days. However, the management of PORT related complications required more visits to the hospital and oncology clinic.
The Impact of Geography in Hepatocellular Carcinoma: A Retrospective Population Based Study
Authors: Yu Irene S. , Liu Shiru L. , Zaborska Valeriya , Raycraft Tyler , Gill Sharlene , Lim Howard , Davies Janine M.
Published: January 2021

Background: The treatment of hepatocellular carcinoma (HCC) includes different therapeutic modalities and multidisciplinary tumor board reviews. The impact of geography and treatment center type (quaternary vs. non-quaternary) on access to care is unclear. Methods: A retrospective chart review was performed on HCC patients who received sorafenib in British Columbia from 2008 to 2016. Patients were grouped by Statistics Canada population center (PC) size criteria: large PC (LPC), medium PC (MPC), and small PC (SPC). Access to specialists, receipt of liver-directed therapies, and survival outcomes were compared between the groups. Results: Of 286 patients, the geographical distribution was: LPC: 75%; MPC: 16%; and SPC: 9%. A higher proportion of Asians (51% vs. 9% vs. 4%; p < 0.001), Child–Pugh A (94% vs. 83% vs. 80%; p = 0.022), and hepatitis B (37% vs. 15% vs. 4%; p < 0.001) was observed in LPC vs. MPC vs. SPC, respectively. LPC patients were more likely referred to a hepatologist (62% vs. 48% vs. 40%; p = 0.031) and undergo transarterial chemoembolization (TACE) (43% vs. 24% vs. 24%; p = 0.018). Sixty percent were treated at a quaternary center, and the median overall survival (OS) was higher for patients treated at a quaternary vs. non-quaternary center (28.0 vs. 14.6 months, respectively; p < 0.001) but similar when compared by PC size. Treatment at a quaternary center predicted an improved survival on multivariate analysis (hazard ratio (HR): 0.652; 95% confidence interval (CI): 0.503–0.844; p = 0.001). Conclusions: Geography did not appear to impact OS but patients from LPC were more likely to be referred to hepatology and undergo TACE. Treatment at a quaternary center was associated with an improved survival.
A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada
Authors: Beaulieu Carissa , Lui Arthur , Yusuf Dimas , Abdelaziz Zainab , Randolph Brock , Batuyong Eugene , Ghosh Sunita , Bathe Oliver F. , Tam Vincent , Spratlin Jennifer L.
Published: January 2021

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19–99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.
Feasibility of a Pilot Randomized Controlled Trial Examining a Multidimensional Intervention in Women with Gynecological Cancer at Risk of Lymphedema
Authors: Shallwani Shirin M. , Towers Anna , Newman Anne , Salvador Shannon , Yung Angela , Gilbert Lucy , Gotlieb Walter H. , Zeng Xing , Thomas Doneal
Published: January 2021

There is limited knowledge on non-invasive lymphedema risk-reduction strategies for women with gynecological cancer. Understanding factors influencing the feasibility of randomized controlled trials (RCTs) can guide future research. Our objectives are to report on the design and feasibility of a pilot RCT examining a tailored multidimensional intervention in women treated for gynecological cancer at risk of lymphedema and to explore the preliminary effectiveness of the intervention on lymphedema incidence at 12 months. In this pilot single-blinded, parallel-group, multi-centre RCT, women with newly diagnosed gynecological cancer were randomized to receive post-operative compression stockings and individualized exercise education (intervention group: IG) or education on lymphedema risk-reduction alone (control group: CG). Rates of recruitment, retention and assessment completion were recorded. Intervention safety and feasibility were tracked by monitoring adverse events and adherence. Clinical outcomes were evaluated over 12 months: presence of lymphedema, circumferential and volume measures, body composition and quality of life. Fifty-one women were recruited and 36 received the assigned intervention. Rates of recruitment and 12-month retention were 47% and 78%, respectively. Two participants experienced post-operative cellulitis, prior to intervention delivery. At three and six months post-operatively, 67% and 63% of the IG used compression ≥42 h/week, while 56% engaged in ≥150 weekly minutes of moderate-vigorous exercise. The cumulative incidence of lymphedema at 12 months was 31% in the CG and 31.9% in the IG (p = 0.88). In affected participants, lymphedema developed after a median time of 3.2 months (range, 2.7–5.9) in the CG vs. 8.8 months (range, 2.9–11.8) in the IG. Conducting research trials exploring lymphedema risk-reduction strategies in gynecological cancer is feasible but challenging. A tailored intervention of compression and exercise is safe and feasible in this population and may delay the onset of lymphedema. Further research is warranted to establish the role of these strategies in reducing the risk of lymphedema for the gynecological cancer population.
Canadian Consensus for Biomarker Testing and Treatment of TRK Fusion Cancer in Adults
Authors: Bebb D. Gwyn , Banerji Shantanu , Blais Normand , Desmeules Patrice , Gill Sharlene , Grin Andrea , Feilotter Harriet , Hansen Aaron R. , Hyrcza Martin , Krzyzanowska Monika , Melosky Barbara , Noujaim Jonathan , Purgina Bibiana , Ruether Dean , Simmons Christine E. , Soulieres Denis , Torlakovic Emina Emilia , Tsao Ming-Sound
Published: January 2021

The tyrosine receptor kinase (TRK) inhibitors larotrectinib and entrectinib were recently approved in Canada for the treatment of solid tumours harbouring neurotrophic tyrosine receptor kinase (NTRK) gene fusions. These NTRK gene fusions are oncogenic drivers found in most tumour types at a low frequency (<5%), and at a higher frequency (>80%) in a small number of rare tumours (e.g., secretory carcinoma of the salivary gland and of the breast). They are generally mutually exclusive of other common oncogenic drivers. Larotrectinib and entrectinib have demonstrated impressive overall response rates and tolerability in Phase I/II trials in patients with TRK fusion cancer with no other effective treatment options. Given the low frequency of TRK fusion cancer and the heterogeneous molecular testing landscape in Canada, identifying and optimally managing such patients represents a new challenge. We provide a Canadian consensus on when and how to test for NTRK gene fusions and when to consider treatment with a TRK inhibitor. We focus on five tumour types: thyroid carcinoma, colorectal carcinoma, non-small cell lung carcinoma, soft tissue sarcoma, and salivary gland carcinoma. Based on the probability of the tumour harbouring an NTRK gene fusion, we also suggest a tumour-agnostic consensus for NTRK gene fusion testing and treatment. We recommend considering a TRK inhibitor in all patients with TRK fusion cancer with no other effective treatment options.
Clinicopathologic and Treatment Features of Long-Term Surviving Brain Metastasis Patients
Authors: Dasgupta Archya , Co Jayson , Winter Jeff , Millar Barbara-Ann , Laperriere Normand , Tsang Derek S. , van Prooijen Monique , Damyanovich Andrei , Heaton Robert , Coolens Catherine , Bernstein Mark , Kongkham Paul , Zadeh Gelareh , Berlin Alejandro , Conrad Tatiana , Moraes Fabio Y. , Shultz David B.
Published: January 2021

Background: The purpose of our study was to characterize clinical features among brain metastasis (BM) patients who were long term survivors (LTS). Methods: We reviewed a registry of BM patients referred to our multidisciplinary BM clinic between 2006 and 2014 and identified 97 who lived ≥ 3 years following BM diagnosis. The clinical and treatment characteristics were obtained from a prospectively maintained database, and additional information was obtained through review of electronic medical records and radiologic images. Survival analyses were performed using the Kaplan-Meier method. Results: Median follow up for LTS was 67 months (range 36–181). Median age was 54 years, 65% had single BM, 39% had stable extracranial disease at the time of BM treatment, and brain was the first site of metastasis in 76%. Targetable mutations were present in 39% of patients and 66% received treatment with targeted-, hormonal-, or immuno-therapy. Brain surgery at the time of diagnosis was performed in 40% and stereotactic radiosurgery (SRS) or whole brain radiotherapy (alone or combination) in 52% and 56%, respectively. Following initial BM treatment, 5-year intracranial disease-free survival was 39%, and the cumulative incidence of symptomatic radio-necrosis was 16%. Five and ten-year overall survival was 72% and 26%, respectively. Conclusion: Most LTS were younger than 60 years old and had a single BM. Many received treatment with surgery or targeted, immune, or hormonal therapy.
Assessment of Breast Cancer Surgery in Manitoba: A Descriptive Study
Authors: Ratnayake Iresha , Hebbard Pamela , Feely Allison , Biswanger Natalie , Decker Kathleen
Published: January 2021

Background: Variation in breast cancer surgical practice patterns can lead to poor clinical outcomes. It is important to measure and reduce variation to ensure all women diagnosed with breast cancer receive equitable, high-quality care. A population-based assessment of the variation in breast cancer surgery treatment and quality has never been conducted in Manitoba. The objective of this study was to assess the variation in surgical treatment patterns, quality of care, and post-operative outcomes for women diagnosed with invasive breast cancer. Methods: This descriptive study used data from the Manitoba Cancer Registry, Hospital Discharge Abstracts Database, Medical Claims, Manitoba Health Insurance Registry, and Statistics Canada. The study included women in Manitoba aged 20+ and diagnosed with invasive breast cancer between 1 January 2010 and 31 December 2014. Results: Axillary lymph node dissection (ALND) for node-negative disease ranged from 3.4% to 32.6%, timeliness (surgery within 30 days of consult) ranged from 33.3% to 60.2%, and re-excision ranged from 14.7% to 24.6% between health authorities. Women who underwent breast-conserving surgery had the shortest median length of stay and women who underwent mastectomy with immediate reconstruction had the longest median length of stay. In-hospital post-operative complications were higher among women who received mastectomy with immediate reconstruction (9.9%). Conclusion: Variation in surgical treatment, quality, and outcomes exist in Manitoba. The findings from this study can be used to inform cancer service delivery planning, quality improvement efforts, and policy development. Influencing data-driven change at the health system level is paramount to ensuring Manitobans receive the highest quality of care.
Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?
Authors: Santoni Matteo , Massari Francesco , Bracarda Sergio , Procopio Giuseppe , Milella Michele , De Giorgi Ugo , Basso Umberto , Aurilio Gaetano , Incorvaia Lorena , Martignetti Angelo , Rizzo Mimma , Cartenì Giacomo , Grande Enrique , Matrana Marc R. , Crabb Simon J. , Vau Nuno , Sorgentoni Giulia , Cimadamore Alessia , Montironi Rodolfo , Battelli Nicola
Published: January 2021

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.
White Matter Microstructural Differences between Hallucinating and Non-Hallucinating Schizophrenia Spectrum Patients
Authors: Beresniewicz Justyna , Craven Alexander R. , Hugdahl Kenneth , Løberg Else-Marie , Kroken Rune Andreas , Johnsen Erik , Grüner Renate
Published: January 2021

The relation between auditory verbal hallucinations (AVH) and white matter has been studied, but results are still inconsistent. This inconsistency may be related to having only a single time-point of AVH assessment in many studies, not capturing that AVH severity fluctuates over time. In the current study, AVH fluctuations were captured by utilizing a longitudinal design and using repeated (Positive and Negative Symptoms Scale) PANSS questionnaire interviews over a 12 month period. We used a Magnetic Resonance Diffusion Tensor Imaging (MR DTI) sequence and tract-based spatial statistics (TBSS) to explore white matter differences between two subtypes of schizophrenia patients; 44 hallucinating (AVH+) and 13 non-hallucinating (AVH-), compared to 13 AVH- matched controls and 44 AVH+ matched controls. Additionally, we tested for hemispheric fractional anisotropy (FA) asymmetry between the groups. Significant widespread FA-value reduction was found in the AVH+ group in comparison to the AVH- group. Although not significant, the extracted FA-values for the control group were in between the two patient groups, for all clusters. We also found a significant difference in FA-asymmetry between the AVH+ and AVH- groups in two clusters, with significantly higher leftward asymmetry in the AVH- group. The current findings suggest a possible qualitative difference in white matter integrity between AVH+ and AVH- patients. Strengths and limitations of the study are discussed.
Costs of Point-of-Care Viral Load Testing for Adults and Children Living with HIV in Kenya
Authors: Bulterys Michelle Ann , Oyaro Patrick , Brown Evelyn , Yongo Nashon , Karauki Enericah , Wagude James , Kingwara Leonard , Bowen Nancy , Njogo Susan , Wagner Anjuli D. , Mukui Irene , Oluoch Frederick , Abuogi Lisa , Patel Rena , Sharma Monisha
Published: January 2021

Background: The number of people living with HIV (PLHIV) in need of treatment monitoring in low-and-middle-income countries is rapidly expanding, straining existing laboratory capacity. Point-of-care viral load (POC VL) testing can alleviate the burden on centralized laboratories and enable faster delivery of results, improving clinical outcomes. However, implementation costs are uncertain and will depend on clinic testing volume. We sought to estimate the costs of decentralized POC VL testing compared to centralized laboratory testing for adults and children receiving HIV care in Kenya. Methods: We conducted microcosting to estimate the per-patient costs of POC VL testing compared to known costs of centralized laboratory testing. We completed time-and-motion observations and stakeholder interviews to assess personnel structures, staff time, equipment costs, and laboratory processes associated with POC VL administration. Capital costs were estimated using a 5 year lifespan and a 3% annual discount rate. Results: We estimated that POC VL testing cost USD $24.25 per test, assuming a clinic is conducting 100 VL tests per month. Test cartridge and laboratory equipment costs accounted for most of the cost (62% and 28%, respectively). Costs varied by number of VL tests conducted at the clinic, ranging from $54.93 to $18.12 per test assuming 20 to 500 VL tests per month, respectively. A VL test processed at a centralized laboratory was estimated to cost USD $25.65. Conclusion: POC VL testing for HIV treatment monitoring can be feasibly implemented in clinics within Kenya and costs declined with higher testing volumes. Our cost estimates are useful to policymakers in planning resource allocation and can inform cost-effectiveness analyses evaluating POC VL testing.
Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes
Authors: Ismail Nurruzanna , Abdullah Noraidatulakma , Abdul Murad Nor Azian , Jamal Rahman , Sulaiman Siti Aishah
Published: January 2021

The discovery of non-coding RNAs (ncRNAs) has opened a new paradigm to use ncRNAs as biomarkers to detect disease progression. Long non-coding RNAs (lncRNA) have garnered the most attention due to their specific cell-origin and their existence in biological fluids. Type 2 diabetes patients will develop cardiovascular disease (CVD) complications, and CVD remains the top risk factor for mortality. Understanding the lncRNA roles in T2D and CVD conditions will allow the future use of lncRNAs to detect CVD complications before the symptoms appear. This review aimed to discuss the roles of lncRNAs in T2D and CVD conditions and their diagnostic potential as molecular biomarkers for CVD complications in T2D.
Comparative Evaluation of Chair-Side Saliva Tests According to Current Dental Status in Adult Patient
Authors: Rahiotis Chris , Mitropoulos Panagiotis , Kakaboura Afrodite
Published: January 2021

Background: this cross-sectional study evaluated the correlation of commercial chair-side saliva tests with caries status in adults. Methods: teeth in 87 adults (20–40 years old) were clinically examined for carious lesions according to International Caries Detection and Assessment System (ICDAS) criteria. The Decayed-Missing-Filling-Tooth (DMFT) and Decayed-Missing-Filling-Surface (DMFS) indexes at D1 (lesions 1–6 according to ICDAS criteria) and D3 (lesions 4–6 according to ICDAS criteria threshold and the number of active lesions, according to the Lesion Activity Assessment (LAA)) criteria were measured. The saliva parameters measured by chair-side tests were stimulated and non-stimulated saliva flow rate, saliva consistency, saliva pH, saliva buffer capacity, and lactic acid production. The statistical analyses performed were Student t-test and Mann–Whitney U test at a = 0.05 significant level. Results: the low resting saliva pH was related to a high value of DMFT (D1) index (p = 0.007). Conclusions: among the saliva parameters measured, the values of low resting pH are associated with increased DMFT at threshold D1. None of the chair-side available saliva tests evaluated can accurately underline the tooth carious status.
Variationally Inferred Sampling through a Refined Bound
Authors: Gallego Víctor , Ríos Insua David
Published: January 2021

In this work, a framework to boost the efficiency of Bayesian inference in probabilistic models is introduced by embedding a Markov chain sampler within a variational posterior approximation. We call this framework “refined variational approximation”. Its strengths are its ease of implementation and the automatic tuning of sampler parameters, leading to a faster mixing time through automatic differentiation. Several strategies to approximate evidence lower bound (ELBO) computation are also introduced. Its efficient performance is showcased experimentally using state-space models for time-series data, a variational encoder for density estimation and a conditional variational autoencoder as a deep Bayes classifier.
Latencies in Power Systems: A Database-Based Time-Delay Compensation for Memory Controllers
Authors: Molina-Cabrera Alexander , Ríos Mario A. , Besanger Yvon , Hadjsaid Nouredine , Montoya Oscar Danilo
Published: January 2021

Time-delay is inherent to communications schemes in power systems, and in a closed loop strategy the presence of latencies increases inter-area oscillations and security problems in tie-lines. Recently, Wide Area Measurement Systems (WAMS) have been introduced to improve observability and overcome slow-rate communications from traditional Supervisory Control and Data Acquisition (SCADA). However, there is a need for tackling time-delays in control strategies based in WAMS. For this purpose, this paper proposes an Enhanced Time Delay Compensator (ETDC) approach which manages varying time delays introducing the perspective of network latency instead dead time; also, ETDC takes advantage of real signals and measurements transmission procedure in WAMS building a closed-loop memory control for power systems. The strength of the proposal was tested satisfactorily in a widely studied benchmark model in which inter-area oscillations were excited properly.
Quality Differences between Fresh and Dried Buckwheat Noodles Associated with Water Status and Inner Structure
Authors: Wang Ruibin , Li Ming , Wei Yimin , Guo Boli , Brennan Margaret , Brennan Charles Stephen
Published: January 2021

Buckwheat noodles are mainly sold in the form of fresh and dried noodles in China. Among the noodles with varied proportions of extruded buckwheat flour (20% to 80%), the cooking or textural qualities of fresh and dried buckwheat noodles (FBN and DBN, respectively) were significantly different, and FBN showed a lower cooking loss and breakage ratio and were more elastic than DBN. FBN-20% showed the highest sensory score, followed by DBN-50%. The mechanisms causing the quality differences were investigated using water mobility and the internal structures of the noodles were investigated with low-field nuclear magnetic resonance and scanning electron microscopy, respectively. Compared with FBN, DBN showed a denser internal structure, which explained its higher hardness. The water within FBN and DBN was mainly in the form of softly bound water and tightly bound water, respectively. FBN with highly mobile softly bound water (longer T22) and a more uniform internal structure had a lower breakage ratio, whereas the trends of water relation with texture properties were different for FBN and DBN. The drying process and added extruded buckwheat flour together contributed to the varied cooking and textural properties.
Bioactive Compounds in Wild Nettle (Urtica dioica L.) Leaves and Stalks: Polyphenols and Pigments upon Seasonal and Habitat Variations
Authors: Repajić Maja , Cegledi Ena , Zorić Zoran , Pedisić Sandra , Elez Garofulić Ivona , Radman Sanja , Palčić Igor , Dragović-Uzelac Verica
Published: January 2021

This study evaluated the presence of bioactives in wild nettle leaves and stalks during the phenological stage and in the context of natural habitat diversity. Thus, wild nettle samples collected before flowering, during flowering and after flowering from 14 habitats situated in three different regions (continental, mountain and seaside) were analyzed for low molecular weight polyphenols, carotenoids and chlorophylls using UPLC-MS/MS and HPLC analysis, while the ORAC method was performed for the antioxidant capacity measurement. Statistical analysis showed that, when compared to the stalks, nettle leaves contained significantly higher amounts of analyzed compounds which accumulated in the highest yields before flowering (polyphenols) and at the flowering stage (pigments). Moreover, nettle habitat variations greatly influenced the amounts of analyzed bioactives, where samples from the continental area contained higher levels of polyphenols, while seaside region samples were more abundant with pigments. The levels of ORAC followed the same pattern, being higher in leaves samples collected before and during flowering from the continental habitats. Hence, in order to provide the product’s maximum value for consumers’ benefit, a multidisciplinary approach is important for the selection of a plant part as well as its phenological stage with the highest accumulation of bioactive compounds.
Physicochemical Properties and Antioxidant Activity of Pumpkin Polysaccharide (Cucurbita moschata Duchesne ex Poiret) Modified by Subcritical Water
Authors: Yu Guoyong , Zhao Jing , Wei Yunlu , Huang Linlin , Li Fei , Zhang Yu , Li Quanhong
Published: January 2021

In this paper, subcritical water (SCW) was applied to modify pumpkin (Cucurbita moschata Duchesne ex Poiret) polysaccharides, and the properties and antioxidant activity of pumpkin polysaccharides were investigated. SCW treatments at varying temperature led to changes in the rheological and emulsifying properties of pumpkin polysaccharides. SCW treatments efficiently degraded pumpkin polysaccharides and changed the molecular weight distribution. Decreases in intrinsic viscosity, viscosity-average molecular weight, and apparent viscosity were also observed, while the activation energy and flow behavior indices increased. The temperature of SCW treatment has a great influence on the linear viscoelastic properties and antioxidant activity of pumpkin polysaccharides. Pumpkin polysaccharides solution treated by SCW at 150 °C exhibited the highest emulsifying activity and antioxidant activity, which was probably due to a broader molecular mass distribution and more reducing ends exposed after treatment. Scanning electron microscopy showed that SCW treatment changed the microstructure of pumpkin polysaccharides, resulting in the exposure of bigger surface area. Our results suggest that SCW treatment is an effective approach to modify pumpkin polysaccharides to achieve improved solution properties and antioxidant activity.
Vitamin C from Seaweed: A Review Assessing Seaweed as Contributor to Daily Intake
Authors: Nielsen Cecilie Wirenfeldt , Rustad Turid , Holdt Susan Løvstad
Published: January 2021

Seaweeds are indiscriminately said to contain significant amounts of vitamin C, but seaweeds are a diverse group, which may limit the ability to generalize. Several studies have been performed on vitamin C in seaweed, and this review covers these findings, and concludes on how much vitamin C is found in seaweeds. A systematic review of vitamin C in 92 seaweed species was conducted followed by analyzing the 132 data entries. The average vitamin C content was 0.773 mg g−1 seaweed in dry weight with a 90th percentile of 2.06 mg g−1 dry weight. The vitamin C content was evaluated based on taxonomical categories of green, brown and red seaweeds (Chlorophyta (phylum), Phaeophyceae (class), and Rhodophyta (phylum)), and no significant differences were found between them. The vitamin C content was compared to other food sources, and this showed that seaweeds can contribute to the daily vitamin C intake, but are not a rich source. Moreover, seasonal variations, analytical methods, and processing impacts were also evaluated.
The Potential of LiDAR and UAV-Photogrammetric Data Analysis to Interpret Archaeological Sites: A Case Study of Chun Castle in South-West England
Authors: Kadhim Israa , Abed Fanar
Published: January 2021

With the increasing demands to use remote sensing approaches, such as aerial photography, satellite imagery, and LiDAR in archaeological applications, there is still a limited number of studies assessing the differences between remote sensing methods in extracting new archaeological finds. Therefore, this work aims to critically compare two types of fine-scale remotely sensed data: LiDAR and an Unmanned Aerial Vehicle (UAV) derived Structure from Motion (SfM) photogrammetry. To achieve this, aerial imagery and airborne LiDAR datasets of Chun Castle were acquired, processed, analyzed, and interpreted. Chun Castle is one of the most remarkable ancient sites in Cornwall County (Southwest England) that had not been surveyed and explored by non-destructive techniques. The work outlines the approaches that were applied to the remotely sensed data to reveal potential remains: Visualization methods (e.g., hillshade and slope raster images), ISODATA clustering, and Support Vector Machine (SVM) algorithms. The results display various archaeological remains within the study site that have been successfully identified. Applying multiple methods and algorithms have successfully improved our understanding of spatial attributes within the landscape. The outcomes demonstrate how raster derivable from inexpensive approaches can be used to identify archaeological remains and hidden monuments, which have the possibility to revolutionize archaeological understanding.
The Formation of the Epiphyseal Bone Plate Occurs via Combined Endochondral and Intramembranous-Like Ossification
Authors: Fernández-Iglesias Ángela , Fuente Rocío , Gil-Peña Helena , Alonso-Durán Laura , Santos Fernando , López José Manuel
Published: January 2021

The formation of the epiphyseal bone plate, the flat bony structure that provides strength and firmness to the growth plate cartilage, was studied in the present study by using light, confocal, and scanning electron microscopy. Results obtained evidenced that this bone tissue is generated by the replacement of the lower portion of the epiphyseal cartilage. However, this process differs considerably from the usual bone tissue formation through endochondral ossification. Osteoblasts deposit bone matrix on remnants of mineralized cartilage matrix that serve as a scaffold, but also on non-mineralized cartilage surfaces and as well as within the perivascular space. These processes occur simultaneously at sites located close to each other, so that, a core of the sheet of bone is established very quickly. Subsequently, thickening and reshaping occurs by appositional growth to generate a dense parallel-fibered bone structurally intermediate between woven and lamellar bone. All these processes occur in close relationship with a cartilage but most of the bone tissue is generated in a manner that may be considered as intramembranous-like. Overall, the findings here reported provide for the first time an accurate description of the tissues and events involved in the formation of the epiphyseal bone plate and gives insight into the complex cellular events underlying bone formation at different sites on the skeleton.
Advances in Growth Factor Delivery for Bone Tissue Engineering
Authors: Oliveira Érica Resende , Nie Lei , Podstawczyk Daria , Allahbakhsh Ahmad , Ratnayake Jithendra , Brasil Dandara Lima , Shavandi Amin
Published: January 2021

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.