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Dr. Jordana Cohen Jordana Cohen, MD, MSCE Assistant Professor of Medicine and Epidemiology Renal-Electrolyte and Hypertension Division Center for Clinical Epidemiology and Biostatistics Perelman School of Medicine University of Pennsylvania MedicalResearch.com: What is the background for this study? Response: In the June 18, 2019 issue of Annals of Internal Medicine, we published a systematic review and meta-analysis evaluating the cardiovascular risks of white coat hypertension (WCH; i.e. elevated office blood pressure and normal out-of-office blood pressure). The goal of the meta-analysis was to clarify previous mixed results regarding the risks of untreated WCH and treated WCH. The meta-analysis examined 27 studies – including 64,273 patients – and demonstrated that untreated WCH is associated with an increased risk of cardiovascular events (36%), all-cause mortality (33%), and cardiovascular mortality (109%) compared to normotension. This risk was strongest in studies with a mean age ≥55 years or that included participants with cardiac risk factors, such as diabetes and chronic kidney disease. We found no increased cardiovascular risk associated with treated white coat hypertension. MedicalResearch.com: What are the main findings? Response: I was invited to give a talk related to this research at the AHA Hypertension Scientific Sessions this past week on the topic of out-of-office BP patterns in women. A prior meta-analysis restricted to cross-sectional studies suggested that women may be at a 3-fold increased risk of white coat hypertension compared to men, though these findings are not consistently demonstrated in the large prospective cohorts that we included in our meta-analysis. Banegas’s New England Journal Study is the only study I have encountered that has specifically evaluated the sex-specific risk of WCH; the authors demonstrated no increased risk of cardiovascular or all-cause mortality among women with WCH compared to men with white coat hypertension. I performed new analyses for the talk, which demonstrated no increased cardiovascular risk associated with WCH among studies with a higher proportion of women who had white coat hypertension, supporting Banegas’s findings. MedicalResearch.com: What should readers take away from your report? Response: The meta-analysis did not demonstrate that individuals with untreated WCH should be initiated on antihypertensive treatment. Instead, individuals with untreated WCH need to be closely monitored with out-of-office blood pressure monitoring. These individuals are at a high risk of developing sustained hypertension; the often-uncaptured transition to sustained hypertension likely drives their increased cardiovascular risk. We also recommend being cautious not to overtreat individuals with treated white coat hypertension, as they may be prone to out-of-office hypotension and unnecessary side effects from medications. MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: Future studies need to assess if initiating patients with white coat hypertension on antihypertensive therapy helps to reduce cardiovascular risk, balanced with the real risk of out-of-office hypotension. MedicalResearch.com: Is there anything else you would like to add? Response: The Center for Medicare Services announced in July 2019 that they will expand reimbursement for ambulatory blood pressure monitoring – which provides the highest quality out-of-office blood pressure readings – to include treated and untreated white coat hypertension and masked hypertension. In individuals who require repeated monitoring over time (e.g., for medication titration), home blood pressure monitoring can be valuable, but requires training on correct technique and use of a validated monitor. The AMA will be coming out with a device listing of validated home BP monitors available in the US by the end of this year. This research was funded by the nih_nhlbi K23-HL133843  Citation: Hypertension 2019 Scientific Sessions abstract Incidence and Prognosis of White Coat Hypertension in Women Jordana Cohen, MD, MSCE  Last Modified: The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.   Read the full article

Objective: To design and fabricate crush-proof tracheal tubes for newborn infants with the lowest resistance, least dead space, and thinnest wall.   The team: An experienced inventor (Dr. Theodor Kolobow), his post-docs (Lorenzo Berra and Lorenzo DeMarchi), and Dr. Hany Ali from George Washington University Hospital. The design: flat nickel titanium shape-memory alloy (Nitinol) tubes, one for breathing in and one for breathing out, attached to a Y-connector.  The result: Dead air space is decreased so the patient doesn't rebreathe air, and more area allows more air in and out.  This work was published in 2004.  https://bit.ly/2FuYznQ    @NIH_NHLBI  @IRPatNIH

Taking over the work of the heart --- oxygenating blood --- so that people with lung or heart damage can recover was Dr. Theodor Kolobow’s long-term goal.  In the late 1960s, he and Dr. Warren Zapol developed an artificial placenta which kept fetal lambs alive.  The system required inventing devices that wouldn’t damage blood as it was pumped. Their method was then tested on human infants in acute respiratory distress, showing it was possible to support patients in acute respiratory failure too.  In 1974, they treated an 11-year old boy who was able to participate in athletics at school just four months after recovering from Acute Respiratory Distress Syndrome (ARDS).  Previously, it was thought that the lungs could not recover from ARDS.  All of this work helped lead to the extracorporeal membrane oxygenation (ECMO) used today, in which the machine replaces the function of the heart and lung for long periods of time and with less damage than the heart-lung machine.  @NIH_NHLBI  @IRPatNIH

I sat down with Dr. Theodor Kolobow and he asked me to breathe through a standard endotracheal tube used with ventilators.  It was difficult.  Then he handed me something he was working on: an ultra-thin walled tube.  That worked much better.  Kolobow was always attempting to find the best way to help patients on ventilators by not harming their lungs or airways, or exposing them to the unnecessary risk of ventilator-acquired pneumonia.  With his stream of post-docs, Kolobow developed cuffed tubes, gilled tubes, mucus slurping tubes, and mucus shaving tubes, along with the ultra-thin walled nitinol tubes.  Many of his designs are now in common use; some are still being accepted by the medical community.  @NIH_NHLBI @IRPatNIH

Dr. Theodor Kolobow became responsible for more than his own research when he became the chief of the Pulmonary and Cardiac Assist Devices Section NHLBI in 1970 --- he added the duty of contract supervision in the NIH Artificial Heart Program.  NIH researchers, universities, and private industry all co-operated to create devices to help diseased hearts.  This Army Pulsatile Pump from Kolobow’s collection was developed by the Walter Reed Army Institute of Research (WRAIR) and the Harry Diamond Laboratories. It propelled blood through a heart/lung machine with less trauma to the blood than a normal pump and oxygenator; the U.S. Army used it during the Vietnam war.   @NIH_NHLBI @IRPatNIH

The NIH was a hotbed of experimental heart surgery in the 1960s.  Dr. Theodor Kolobow contributed by working on how to make operating on the heart easier.  The heart-lung machine oxygenated and circulated blood around the heart, enabling surgeons to operate on a stopped heart.  But the heart-lung machine was huge and difficult to clean.  So, while looking for the best way to oxygenate blood, Kolobow developed the small, disposable heart-lung device described in this 1964 NIH Record article.  While this invention did not replace the heart-lung machine, it did inform Kolobow’s pioneering work on extracorporeal membrane oxygenation (ECMO).  More on that later.  @NIH_NHLBI @IRPatNIH

The first photo explains how the membrane oxygenator works.  The second photo is a huge machine that Kolobow constructed in the basement of Building 31 to make ultra-thin membranes without holes.  Dr. Kolobow is in the foreground.  They had to do the work at night, because the smell bothered everyone else in the building.  

Quote from “Ted Kolobow,” Luciano Gattinoni, Antonio Pesenti, Lorenzo Berra, and Robert Bartlett, Intensive Care Medicine (2018) 44:551–552  https://link.springer.com/article/10.1007/s00134-018-5162-4