Publications by authors named "J Paul Knox"

1,269 Publications

  • Page 1 of 1

Prognostic value of early changes in CT-measured body composition in patients receiving chemotherapy for unresectable pancreatic cancer.

Eur Radiol 2021 May 2. Epub 2021 May 2.

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.

Objectives: Skeletal muscle mass is a prognostic factor in pancreatic ductal adenocarcinoma (PDAC). However, it remains unclear whether changes in body composition provide an incremental prognostic value to established risk factors, especially the Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1). The aim of this study was to determine the prognostic value of CT-quantified body composition changes in patients with unresectable PDAC starting chemotherapy.

Methods: We retrospectively evaluated 105 patients with unresectable (locally advanced or metastatic) PDAC treated with FOLFIRINOX (n = 64) or gemcitabine-based (n = 41) first-line chemotherapy within a multicenter prospective trial. Changes (Δ) in skeletal muscle index (SMI), subcutaneous (SATI), and visceral adipose tissue index (VATI) between pre-chemotherapy and first follow-up CT were assessed. Cox regression models and covariate-adjusted survival curves were used to identify predictors of overall survival (OS).

Results: At multivariable analysis, adjusting for RECISTv1.1-response at first follow-up, ΔSMI was prognostic for OS with a hazard ratio (HR) of 1.2 (95% CI: 1.08-1.33, p = 0.001). No significant association with OS was observed for ΔSATI (HR: 1, 95% CI: 0.97-1.04, p = 0.88) and ΔVATI (HR: 1.01, 95% CI: 0.99-1.04, p = 0.33). At an optimal cutoff of 2.8 cm/m per 30 days, the median survival of patients with high versus low ΔSMI was 143 versus 233 days (p < 0.001).

Conclusions: Patients with a lower rate of skeletal muscle loss at first follow-up demonstrated improved survival for unresectable PDAC, regardless of their RECISTv1.1-category. Assessing ΔSMI at the first follow-up CT may be useful for prognostication, in addition to routine radiological assessment.

Key Points: • In patients with unresectable pancreatic ductal adenocarcinoma, change of skeletal muscle index (ΔSMI) in the early phase of chemotherapy is prognostic for overall survival, even after adjusting for Response Evaluation Criteria in Solid Tumors version 1.1 (RECISTv1.1) assessment at first follow-up. • Changes in adipose tissue compartments at first follow-up demonstrated no significant association with overall survival. • Integrating ΔSMI into routine radiological assessment may improve prognostic stratification and impact treatment decision-making at the first follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-021-07899-6DOI Listing
May 2021

Prolonged Viral Shedding in Patients with Mild to Moderate COVID-19 Disease: A Regional Perspective.

Infect Dis (Auckl) 2021 13;14:11786337211010428. Epub 2021 Apr 13.

Internal Medical Services, Ballarat Health Services, Ballarat, VIC, Australia.

Background: The risk of transmission of Coronavirus Disease 2019 (COVID-19) is increasingly understood to be greatest early after symptom onset, however, factors associated with prolonged and increased risk of transmission remain unclear. In settings where COVID-19 prevalence is low, there may be a benefit of extending the period that patients are isolated to decrease the risk of transmission. This study explored the duration of viral shedding in such a location, in patients with mild-moderate COVID-19 disease in Ballarat, Australia.

Methods: Patients diagnosed with COVID-19 disease using a real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay from oropharyngeal and bilateral deep nasopharyngeal sampling and managed through Ballarat Health Services between March 1 and May 1, 2020 were included. Patients were retested if they were afebrile for >72 hours, asymptomatic and >14 days since symptom onset. If positive on retesting, patients were tested every 3 to 7 days thereafter.

Results: Patients underwent testing a median of 4 days (range 1-12) after initial symptom onset. Duration of symptoms ranged from 1 to 36 days. Positive tests were recorded up to a median of day 21 (range 6-38). Cycle thresholds were inversely correlated with time since symptom onset ( < .0001). Median time to the first negative test was 25 days (range 12-32). Two patients who had remained asymptomatic for >7 days after initial symptom onset had recrudescence of mild symptoms on day 13 and 14; both tested positive on follow-up tests at this time.

Conclusions: This study demonstrates prolonged shedding of COVID-19 in patients with mild-moderate disease. It suggests that some patients with mild disease may have recrudescence of symptoms a week or more after their initial symptoms resolved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/11786337211010428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047841PMC
April 2021

A survey of the kinome pharmacopeia reveals multiple scaffolds and targets for the development of novel anthelmintics.

Sci Rep 2021 Apr 28;11(1):9161. Epub 2021 Apr 28.

Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada.

Over one billion people are currently infected with a parasitic nematode. Symptoms can include anemia, malnutrition, developmental delay, and in severe cases, death. Resistance is emerging to the anthelmintics currently used to treat nematode infection, prompting the need to develop new anthelmintics. Towards this end, we identified a set of kinases that may be targeted in a nematode-selective manner. We first screened 2040 inhibitors of vertebrate kinases for those that impair the model nematode Caenorhabditis elegans. By determining whether the terminal phenotype induced by each kinase inhibitor matched that of the predicted target mutant in C. elegans, we identified 17 druggable nematode kinase targets. Of these, we found that nematode EGFR, MEK1, and PLK1 kinases have diverged from vertebrates within their drug-binding pocket. For each of these targets, we identified small molecule scaffolds that may be further modified to develop nematode-selective inhibitors. Nematode EGFR, MEK1, and PLK1 therefore represent key targets for the development of new anthelmintic medicines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88150-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080662PMC
April 2021

Mobile app development in health research: pitfalls and solutions.

Mhealth 2021 20;7:32. Epub 2021 Apr 20.

Bridge HIV, San Francisco Department of Public Health, San Francisco, CA, USA.

Mobile app health research presents myriad opportunities to improve health, and simultaneously introduces a new set of challenges that are non-intuitive and extend beyond typical training received by researchers. Informed by our experiences with app development for health research, we discuss some of the most salient pitfalls when working with emerging technology as well as potential strategies to avoid or resolve these challenges. To address challenges at the project level, we suggest strategies that researchers can use to future-proof their research, such as using theory and involving those with app development expertise as part of a research team. At the structural level, we include a new model to characterize the relationship between technology- and research-timelines, and provide ideas regarding how to best address this challenge. Given that screen-based time now predominates our lived experiences, it is important that health researchers have the capacity and structural support to develop interventions that utilize these technologies, assess them rigorously, and ensure their timely and equitable dissemination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/mhealth-19-263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063010PMC
April 2021

A Risk Score Model for Locoregional Recurrence Following Upfront Surgery for Pancreatic Adenocarcinoma: Implications for Adjuvant Therapy.

Clin Oncol (R Coll Radiol) 2021 Apr 16. Epub 2021 Apr 16.

Princess Margaret Cancer Center, Department of Radiation Oncology, Toronto, Canada. Electronic address:

Aims: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF.

Materials And Methods: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF.

Results: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001).

Conclusion: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clon.2021.03.007DOI Listing
April 2021