A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, personalized medicine (PM). To achieve the implementation of PM concept into the daily practice including clinical cardiology, it is necessary to create a fundamentally new strategy based upon the subclinical recognition of bioindicators (biopredictors and biomarkers) of hidden abnormalities long before the disease clinically manifests itself.

Each decision-maker values the impact of their decision to use PM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment to thus provide more tailored measures for the patients and persons-at-risk resulting in improved outcomes whilst securing the healthy state and wellness, reduced adverse events, and more cost effective use of health care resources. One of the most advanced areas in cardiology is atherosclerosis, cardiovascular and coronary disorders as well as in yocarditis. A lack of medical guidelines has been identified by the majority of responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PM into the daily practice of cardiologists!

Implementation of PM requires a lot before the current model “physician-patient” could be gradually displaced by a new model “medical advisor-healthy person-at-risk”. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PM to elicit the content of The new branch.

A spectrum of studies showed that specific innate immune responses, various immune cell types and their cross-talks, and the associated inflammatory activities are involved in tumor metastasis. Metastatic tumor activities are now also known to be strongly affected by the surrounding or even “remote” tumor microenvironment(s). These findings strongly suggest that by modulating and regulating specific immune cell responses and/or mechanism-defined molecular and cellular inflammation-suppressive activities, we could now design new approaches for therapeutics or treatment of cancer metastasis. Interestingly, increasing evidences have started to show that specific phytochemicals from certain medicinal herbs may confer functional specificity (e, g., anti-dermatitis activity, suppressing severe inflammation, promoting wound-healing), and  a number of medicinal phytochemicals have been used traditionally for hundreds to thousands of years. Some of such activities recently have also been re-established for their “strong anti-inflammatory” activities at the cellular and tissue levels, and we consider these activities can be evaluated toward the control of specific anti-inflammation at the organ/tissue levels.

With these observations and information, my laboratory has investigated a group of phytoextracts and the derived pure phytochemicals from specific medicinal plants, and evaluated their bioactivities/effects, in vitro and in vivo. For potential future use as personal or precision medicine application, we have used the ex-vivo “primary cultures”, including dendritic cells, MDSCs, Th17, Tregs and other immune cell types in mouse or human models relevant to specific tumor metastasis systems. Experimentally, we employed functional genomics, proteomics, signaling pathway bio-informatics analysis, cytokine/chemokine profiling, micro RNA arrays and RNAseq analysis in various cross-examination studies. Results and findings published in several key papers during the past few years will be discussed and projected for future medicinal research directions, including specifically the development of autologous, personalized tumor vaccines for use by individual cancer patients. 

Pharmacogenetics is proving to be one of the earliest and most valuable applications of precision medicine. This talk is based upon the experience of a company that has provided pharmacogenetics reports for 1.2 million patients since 2013. It will describe some of the best practices that effective programs have instituted for successful adoption. Topics will include test selection, technology considerations, organizational best practices, and some insights into the future of the field.

The time has come where imaging biomarkers are gaining acceptance beyond tumor quantification for Oncology.    This session will cover the creation of a Digital Physical Examination to directly measure major vital organs & tissues, from a whole body perspective, based on non-invasive imaging for a wide range of conditions and diseases beyond Oncology.

With increasing focus on genomic, metabolomic, and molecular quantification of the human body for use in precision medicine, the development of diagnostics, therapeutics, and monitoring of disease progression/treatment takes on a greater role for more effective outcomes. The majority of advances have not included the phenotype, or observable characteristics of an individual resulting from the interaction of its genotype with the environment.

Biomarkers provide researchers and clinicians with useful measurements that allow for earlier diagnosis before a patient begins to show signs of symptoms, and also quantitatively show that a treatment is performing effectively. Technology is now available to measure multiple vital organs & tissues for an integrated exam using non-invasive imaging to acquire data, automation algorithms to quantify images, & AI to develop predictive analytics. A Software-as-a-Service platform enables scalable access to the latest imaging technology, and support for legacy scanners, while improving accuracy, precision, and standardization across imaging facilities.

One of the hallmarks of cancer is genomic instability, which has been studied extensively in tumor cell lines. It has been much more difficult to study how DNA damage response (DDR) pathways operate in living tumors. Therefore, we developed several techniques to grow short term tumor cell cultures or tumor slices ‘ex vivo’ and study the DDR by inducing DNA damage in cultured tumor cells or slices. Several DNA repair proteins accumulate as visible foci on DNA double strand breaks (DSBs). We used this phenomenon to study accumulation of the general markers of DNA breaks (gamma-H2AX and 53BP1) and the homologous recombination repair pathway (RAD51) after DSB induction. BRCA1 or BRCA2 deficiency has been shown before to lead to a defect in RAD51 foci formation. We were able to show that BRCA1 deficient and proficient xenograft tumors could be discriminated well on the basis of this assay. We also screened human tumors and found that a BRCA1 deficient tumor metastasis was RAD51 foci deficient, while most sporadic tumors were proficient. Interestingly, we were also able to identify a sporadic tumor that was RAD51 foci deficient. This tumor slice also showed high sensitivity to PARP inhibitor treatment, another hallmark of BRCA1/2 deficient cells. Therefore, we conclude that we developed a robust assay for identifying BRCAdeficient tumors, which will be important to select patients for PARP inhibitor treatment. Furthermore, other therapeutic interventions can also be tested in this system, which maintains tumor slice integrity and proliferation for at least one week.

Major Depression is common in late life.  It not only causes suffering but it contributes to disability aggravates the course of medical illness and increases mortality.  Both psychotherapy and antidepressants are effective in late life depression.  In a systematic review of older depressed adults we found 27 trials of psychotherapy with 37 comparisons and 2,245 subjects. Psychotherapy was more effective than the control condition but the effect size varied greatly with the type of control.  Trials with waitlist controls showed a large effect size while those with a supportive therapy control had a smaller effect similar to that of antidepressant treatment.  Problem Solving Therapy had the best evidence for efficacy.  We conducted a systematic review of second generation antidepressants in community dwelling adults 60 years and older with Major Depression. 10 trials with 4,165 subjects demonstrated antidepressants were more effective than placebo but the effect size was small resulting in a number-needed-to-treat of 11.  We were able to obtain individual patient data from the sponsors of each of the 10 studies with which we performed a patient level analysis of moderators of antidepressant response. Interestingly age was not a significant moderator. The primary moderator was the lifetime duration of Major Depression. The longer the duration, the lower the placebo response and the greater the drug placebo difference. The finding was replicated in a mixed age sample. 

Delirium is a neuropsychiatric diagnosis that is very common in general medical and surgical populations but of particular importance in palliative medicine.  The incidence is twice that of a regular nursing floor averaging 30%.  At end-of-life the percentage may be as high as 88%. Several different pathophysiologies have been investigated to define the underlying mechanisms to enable targeted therapy. The most commonly accepted cause is a decrease in acetylcholine and increased dopamine. 

Presentation:

 Delirium is a syndrome with myriad presentation usually divided into motoric subtypes -hypoactive, hyperactive and mixed. It is underdiagnosed particularly the hypoactive subgroup which may be more common in the palliative medicine population and may be confused with depression. Medications are the most common causes and unfortunately, the majority of medications used in palliative medicine have the potential to cause delirium.

Treatment:

Treatment of delirium is removing the offending cause when possible. When this is not possible or while waiting for improvement, various antipsychotic medications have been used. The medication with the most data is haloperidol. No atypical antipsychotic has been found to be better that haloperidol but they may be useful if toxicity develops or there is no response. A recent article addressed the use of antipsychotics in those with mild to delirium and there was no benefit.

Consequences: 

The presence of delirium is a predictor of increased morbidity and mortality, longer hospitalization and more likely discharge to a nursing facility. This presentation will review the pathophysiology, etiology, diagnosis and treatment of delirium in palliative medicine