Predicting time to castration resistance in hormone sensitive prostate cancer by a personalization algorithm based on a mechanistic model integrating patient data.

BACKGROUND: Prostate cancer (PCa) is a leading cause of cancer death of men worldwide. In hormone-sensitive prostate cancer (HSPC), androgen deprivation therapy (ADT) is widely used, but an eventual failure on ADT heralds the passage to the castration-resistant prostate cancer (CRPC) stage. Because predicting time to failure on ADT would allow improved planning of personal treatment strategy, we aimed to develop a predictive personalization algorithm for ADT efficacy in HSPC patients. METHODS: A mathematical mechanistic model for HSPC progression and treatment was developed based on the underlying disease dynamics (represented by prostate-specific antigen; PSA) as affected by ADT. Following fine-tuning by a dataset of ADT-treated HSPC patients, the model was embedded in an algorithm, which predicts the patient's time to biochemical failure (BF) based on clinical metrics obtained before or early in-treatment. RESULTS: The mechanistic model, including a tumor growth law with a dynamic power and an elaborate ADT-resistance mechanism, successfully retrieved individual time-courses of PSA (R(2) = 0.783). Using the personal Gleason score (GS) and PSA at diagnosis, as well as PSA dynamics from 6 months after ADT onset, and given the full ADT regimen, the personalization algorithm accurately predicted the individual time to BF of ADT in 90% of patients in the retrospective cohort (R(2) = 0.98). CONCLUSIONS: The algorithm we have developed, predicting biochemical failure based on routine clinical tests, could be especially useful for patients destined for short-lived ADT responses and quick progression to CRPC. Prospective studies must validate the utility of the algorithm for clinical decision-making.

Ventricular arrhythmias due to left ventricular noncompaction cardiomyopathy: a diagnosis in hindsight.

Left ventricular noncompaction cardiomyopathy is a rare congenital cardiomyopathy which predisposes to sudden cardiac death. We describe the case of a 24 year-old man who had previously received an implantable cardioverter-defibrillator for sustained ventricular tachycardia and was later diagnosed with left ventricular noncompaction cardiomyopathy during a hospitalisation for device infection.

Design and Implementation of a Skilled Nursing Facility COVID-19 Unit.

Coronavirus disease 2019 (COVID-19) has challenged the health care system's capacity to care for acutely ill patients. In a collaborative partnership between a health system and a skilled nursing facility (SNF), we developed and implemented an SNF COVID-19 unit to allow expedited hospital discharge of COVID-positive older adults who are clinically improving, and to provide an alternative to hospitalization for those who require SNF care but do not require or necessarily desire aggressive disease-modifying interventions.

Whole blood defensin mRNA expression is a predictive biomarker of docetaxel response in castration-resistant prostate cancer.

This study tested the potential of circulating RNA-based signals as predictive biomarkers for docetaxel response in patients with metastatic castration-resistant prostate cancer (CRPC). RNA was analyzed in blood from six CRPC patients by whole-transcriptome sequencing (total RNA-sequencing) before and after docetaxel treatment using the Illumina's HiSeq platform. Targeted RNA capture and sequencing was performed in an independent cohort of ten patients with CRPC matching the discovery cohort to confirm differential expression of the genes. Response to docetaxel was defined on the basis of prostate-specific antigen levels and imaging criteria. Two-way analysis of variance was used to compare differential gene expression in patients classified as responders versus nonresponders before and after docetaxel treatment. Thirty-four genes with two-fold differentially expressed transcripts in responders versus nonresponders were selected from total RNA-sequencing for further validation. Targeted RNA capture and sequencing showed that 13/34 genes were differentially expressed in responders. Alpha defensin genes DEFA1, DEFA1B, and DEFA3 exhibited significantly higher expression in responder patients compared with nonresponder patients before administration of chemotherapy (fold change >2.5). In addition, post-docetaxel treatment significantly increased transcript levels of these defensin genes in responders (fold change >2.8). Our results reveal that patients with higher defensin RNA transcripts in blood respond well to docetaxel therapy. We suggest that monitoring DEFA1, DEFA1B, and DEFA3 RNA transcripts in blood prior to treatment will be helpful to determine which patients are better candidates to receive docetaxel chemotherapy.

Two rare forms of hepatocellular carcinoma metastases.

An 80-year-old man with known metastatic hepatocellular carcinoma, not on current treatment, was presented with bleeding gingival and penile masses. Bleeding from both sites was able to be controlled with local treatment and subsequent discontinuation of his clopidogrel. The gingival mass was biopsied and was found consistent with metastatic hepatocellular carcinoma. Owing to the concern of recurrent bleeding, the penile mass was not biopsied. Given the significant progression of his disease, the patient was discharged to hospice care.