Previous studies on prostate cancer modeling under hormonal therapy successfully fit clinical serum androgen data, under the assumption that the levels of intracellular and serum androgen are similar. However, such an assumption may not hold throughout the course of treatment. In this paper, we propose a model that directly accounts for serum androgen and its interaction with intracellular androgen. We establish biological links between the model and clinical data, and discuss in detail parameter ranges and the initialization of model variables. We further investigate parameter sensitivity over time, which gauges the maximum effect of varying each parameter and allows us to fix some parameters, to increase the robustness of the parameter fitting process. By relying on the characteristics of intermittent androgen suppression therapy (IAS), we employ a two-part weighted error function for fitting. We also carry out mathematical analyses to study the dynamic aspects of the system with different androgen thresholds. We find that the proposed model shows superior forecasting ability, compared to its predecessor. Furthermore, we demonstrate the impact of androgen on the dynamics of the androgen-dependent and -independent cancer cells, which suggests the discrete description of androgen dependency may not give a realistic characterization of the cancer population. We show that IAS has certain characteristics that need to be considered for parameter estimation. Our results demonstrate that the model and the fitting scheme are viable for similar applications of prostate cancer modeling under hormonal therapy.

Key Points Question What is the prognostic significance of esophageal tumor human papillomavirus (HPV) status? Findings In this case-control study involving 142 patients with Barrett high-grade dysplasia and esophageal adenocarcinoma, HPV positivity was associated with a significantly improved disease-free survival compared with viral negativity. Recurrence and progression were reduced in the HPV-positive cohort as were distant metastasis and death from esophageal adenocarcinoma. Meaning Barrett high-grade dysplasia and esophageal adenocarcinoma in patients who are HPV positive have a favorable prognosis compared with viral-negative esophageal tumors and may benefit from treatment de-escalation.

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Background:Invasive candidiasis (IC) is associated with increased morbidity in severe acute pancreatitis (SAP). There is limited information regarding the predisposing factors, Candida species distribution and in vitro susceptibility.Methodology:Current data have been derived from a larger prospective nonintervention study conducted on 200 critically ill patients which was done to study the antifungal prescription practices, collect epidemiological data, and perform an external validation of risk prediction models for IC under senior research associateship program of Council of Scientific and Industrial Research New Delhi. Of these critically ill patients, thirty had SAP and were included for analysis.Results:There were 23 males and 7 females. Out of eight patients (27%) who developed IC, three had isolated candidemia, two had isolated deep-seated candidiasis while three had both candidemia and deep-seated candidiasis. SAP patients with IC had a longer duration of Intensive Care Unit stay, hospital stay, days on mechanical ventilation and duration of shock. Mortality was not different between SAP patients with or without IC.Conclusion:There is a high rate of Candida infection in SAP. More studies are needed to generate epidemiological data and develop antifungal stewardship in this subset of high-risk population.

IMPORTANCE The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. OBJECTIVE To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. DESIGN, SETTING, AND PARTICIPANTS This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was