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.

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.

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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

SUMMARY There is evidence to suggest that human papillomaviruses (HPV) are associated with Barrett's dysplasia and esophageal adenocarcinoma. In other HPV-linked cancers such as cervical and oropharyngeal cancer, circulating HPV DNA is a potential biomarker to assist in tumor diagnosis and management. This study aimed to determine whether circulating HPV DNA was detectable in patients with Barrett's dysplasia and esophageal adenocarcinoma, and if so, whether there is any correlation with esophageal tissue HPV status. Plasma from 138 patients representing esophageal adenocarcinoma (N = 41), Barrett's dysplasia (N = 48) and hospital controls (N = 49) were analyzed for the presence of circulating HPV DNA using droplet-digital PCR targeting the E7 gene of HPV types 16 and 18. Circulating HPV DNA was detected in 11/138 (8.0%) study subjects including 1/49 (2.0%) hospital controls, 4/48 (8.3%) Barrett's dysplasia patients, and 6/41 (14.6%) esophageal adenocarcinoma patients. Detection of circulating HPV DNA was higher in patients with HPV-positive esophageal tissue (6/35, 17.1%) compared to those with HPV-negative specimens (5/103; 4.9%) (OR = 4.06; 95% CI 1.15–14.25; P = 0.020). The highest rates of detection occurred in esophageal adenocarcinoma patients, particularly those with invasive tumors that had breached the esophageal submucosa, had regional lymph node involvement or metastatic disease. Circulating HPV DNA was detectable in a subset of Barrett's dysplasia and esophageal adenocarcinoma patients. Detection was associated with tissue HPV positivity and possibly disease severity.

Background:The aim of this study was to conduct external validation of risk prediction scores for invasive candidiasis.Methods:We conducted a prospective observational study in a 12-bedded adult medical/surgical Intensive Care Unit (ICU) to evaluate Candida score >3, colonization index (CI) >0.5, corrected CI >0.4 (CCI), and Ostrosky's clinical prediction rule (CPR). Patients' characteristics and risk factors for invasive candidiasis were noted. Patients were divided into two groups; invasive candidiasis and no-invasive candidiasis.Results:Of 198 patients, 17 developed invasive candidiasis. Discriminatory power (area under receiver operator curve [AUROC]) for Candida score, CI, CCI, and CPR were 0.66, 0.67, 0.63, and 0.62, respectively. A large number of patients in the no-invasive candidiasis group (114 out of 181) were exposed to antifungal agents during their stay in ICU. Subgroup analysis was carried out after excluding such patients from no-invasive candidiasis group. AUROC of Candida score, CI, CCI, and CPR were 0.7, 0.7, 0.65, and 0.72, respectively, and positive predictive values (PPVs) were in the range of 25%–47%, along with negative predictive values (NPVs) in the range of 84%–96% in the subgroup analysis.Conclusion:Currently available risk prediction scores have good NPV but poor PPV. They are useful for selecting patients who are not likely to benefit from antifungal therapy.

Background: The pediatric risk of mortality (PRISM) score allows assessment of the severity of illness and mortality risk adjustment in heterogeneous groups of the patients in an objective manner. It has been developed and validated mostly at pediatric intensive care unit (PICUs) of developed countries with very few reports from India. Objectives: This study was planned to evaluate the usefulness of the PRISM score and to correlate it with the mortality in patients admitted to PICU of a northern Indian PICU. Material and Methods: A prospective, observational study was conducted between January 2012 and June 2013, during which a totalof 150 consecutive cases were enrolled for the study. PRISM score was calculated within 24 h of their admission and receiver operating characteristic (ROC) curve was used to establishing the validity of the PRISM score for predicting the mortality. Results: Overall mortality was 12.5%, and the PRISM score for survivors versus non-survivors was 7.5878 ± 5.032 versus 20.63 ± 3.41, respectively. No difference was seen between the observed and expected value of mortality calculated from PRISM score (Z = 0.467-1.521, p = 0.291– 0.64), thereby establishing the validity of the PRISM score in predicting the mortality in our PICU (ROC curve - area under the curve 0.934). The observed and expected values of the mortality were more comparable for lower PRISM scores (0-15) and a PRISM score of 13.5 has the highest sensitivity and specificity. Conclusion: We concluded that PRISM score is a valid parameter to predict the mortality among the ICU patients in Indian set ups.