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Successful use of CAR-T therapy in a solid tumor Chimeric Antigen Reception T-cells (CAR-T) are immune cells molecularly engineered to seek out and destroy cancer cells; the push to develop them into a scalable generally usable treatment is likely the most exciting challenge in cancer right now.  Successful CAR-T use has so far been generally confined to hematological tumors.  In a brief report, a group from City of Hope reports on the use of CAR-T in a patient who was dying from an advanced, aggressive form of brain cancer, which led to a regression of the tumors for several months. Read More

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“My name is T-Cell…, James T-Cell” Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of immune killing of tumor cells. Amplifying results from last year… Read More

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I am not sure how many docs continue to do this, but I still read the actual hard copy of my NEJM, and that means I flip past ad pages with smiling grandfathers playing with grandchildren thanks to supercalifragilistic products on my way to scholarly papers with tables and figures.  But this time, I stopped in puzzlement when I came across exhibit 1; Intermountain is a health system based in Utah, very highly respected for its sound approach to quality and cost control[1], but not broadly well known for cancer care in the way of centers like Dana Farber… Read More

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Continued progress in multiple myeloma About 25,000 patients are diagnosed with multiple myeloma yearly in the US. Despite being initially treatable, typically this disease is ultimately lethal. Following a highly successful phase 1-2 study a monoclonal antibody against a marker of myeloma cells (daratumumab, Janssen) underwent phase 3 studies in combinations with established mainstays of therapy (the proteasome inhibitor bortezomib and the immune modulator lenalinomide) in a patient population several years out from their initial diagnosis.  Results were stellar, with the inclusion of daratumumab decreasing the disease progression rate by half at 1 year.  Daratumumab, Lenalidomide, and Dexamethasone… Read More

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There is such a thing as too much hygiene The prevalence of asthma in children has increased dramatically over the last few decades. Observational studies have shown that children in “dirty” environments such as farms seem to be relatively protected from asthma.  A theory is that the lack of exposure to microbes leads to higher sensitivity to allergens, but this causality has been hard to show. Amish and Hutterite farm communities are genetically similar, but Amish rely on animals instead of machinery, and Amish children have much lower incidence of asthma. In a fascinating study comparing Amish and Hutterite, it… Read More

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Adaptive clinical trials slowly coming of age In an adaptive clinical trial, the protocol of the trial is allowed to change in a pre-specified manner during the study based on on-going study events.  In this issue of the NEJM, two research papers, one perspective, and one editorial are devoted to the I-SPY 2 trials which dynamically changed randomization procedures for neo-adjuvant (pre-surgery) chemotherapy for stage II and III breast cancer and allowed accelerated identification of subgroups that benefit from a novel tyrosine kinase inhibitor (neratinib – Puma Biotechnology) and a PARP inhibitor (veliparib – Abbvie).  Adaptive trials are described in… Read More

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Could Uber happen to healthcare? A Perspective article that points out that the success of Uber is rooted in the flaws of an industry where customer convenience and value for money took the backseat to the interest of a set of service providers highly protected by regulation. Sounds familiar?  Obviously, the regulatory moats of healthcare are much wider and deeper, but in a curious mix of warning (watch out!) and encouragement (this will be good for you if you embrace it!) the authors argue that the medical profession should not consider themselves immune from the disruption that has affected… Read More

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Defining success in health care A perspective advertising yeoman’s work of the International Consortium for Health Outcomes Measurement (ICHOM) which has defined specific metrics for dozens of diseases for which there are no widely accepted standards defined so far. If followed broadly, this will greatly facilitate performance comparisons across systems, improvement of processes of care delivery, and the implementation of value based contracting. Standardizing Patient Outcomes Measurement (free access)   Public health gets no respect A lament on how population health interventions tend to be beholden to positive ROI standards (i.e. will we save money by keeping at… Read More

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A new focus on the diagnostic reliability of clinicians Two perspectives highlighting the recent report from the National Academy of Medicine (formerly IOM) entitled “Improving Diagnosis in Health Care”.  Diagnostic error has long been the invisible side of poor medicine compared to medication errors, or a towel forgotten inside the patient and the like.  But the growth of health IT is both exposing diagnostic error and bearing the seeds of a solution, initially through rule-based automated checks and reminders, but likely eventually through a much more guideline driven practice of medicine with clinical decision support tools.   Reducing Diagnostic Errors… Read More

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What are annual physicals for? Annual physicals are costly (~$10 billion annually) and have never been shown to improve outcomes, but people value them. In this dichotomy lies a lot of the inner tensions of medical care: between delivery of technical care, and nurturing of human relationships, and those are illuminated by two articles in counterpoint.  In the end though both sides come to a point of view that is not altogether dissimilar – that what is needed is not an annual physical, but some sort of preventive care/health review visit which, instead of being a fishing expedition for problems… Read More