Brain-Aging Gene Discovered

Genetic variant accelerates normal brain aging in older people by up to 12 years

Newswise, March 20, 2017—Columbia University Medical Center (CUMC) researchers have discovered a common genetic variant that greatly impacts normal brain aging, starting at around age 65, and may modify the risk for neurodegenerative diseases.

 The findings could point toward a novel biomarker for the evaluation of anti-aging interventions and highlight potential new targets for the prevention or treatment of age-associated brain disorders such as Alzheimer’s disease.

The study was published online   in the journal Cell Systems.

“If you look at a group of seniors, some will look older than their peers and some will look younger,” said the study’s co-leader Asa Abeliovich, PhD, professor of pathology and neurology in the Taub Institute for Alzheimer's Disease and the Aging Brain at CUMC.

“The same differences in aging can be seen in the frontal cortex, the brain region responsible for higher mental processes. Our findings show that many of these differences are tied to variants of a gene called TMEM106B. People who have two ‘bad’ copies of this gene have a frontal cortex that, by various biological measures, appears 12 years older that those who have two normal copies.”

Studies have identified individual genes that increase one’s risk for various neurodegenerative disorders, such as apolipoprotein E (APOE) for Alzheimer's disease.

“But those genes explain only a small part of these diseases,” said study co-leader Herve Rhinn, PhD, assistant professor of pathology and cell biology in the Taub Institute.

“By far, the major risk factor for neurodegenerative disease is aging. Something changes in the brain as you age that makes you more susceptible to brain disease. That got us thinking, ‘What, on a genetic level, is driving healthy brain aging?’”

In the current study, Drs. Abeliovich and Rhinn analyzed genetic data from autopsied human brain samples taken from 1,904 people without neurodegenerative disease. First, the researchers looked at the subjects’ transcriptomes (the initial products of gene expression), compiling an average picture of the brain biology of people at a given age.

Next, each person’s transcriptome was compared to the average transcriptome of people at the same age, looking specifically at about 100 genes whose expression was found to increase or decrease with aging.

From this comparison, the researchers derived a measure that they call differential aging: the difference between an individual’s apparent (biological) age and his or her true (chronological) age. “This told us whether an individual’s frontal cortex looked older or younger than expected,” said Dr. Abeliovich.

The researchers then searched the genome of each individual, looking for genetic variants that were associated with an increase in differential age.

“One variant stood out: TMEM106B,” said Dr. Rhinn. “It’s very common. About one-third of people have two copies and another third have one copy.”

“TMEM106B begins to exert its effect once people reach age 65,” said Dr. Abeliovich. “Until then, everybody’s in the same boat, and then there’s some yet-to-be-defined stress that kicks in. If you have two good copies of the gene, you respond well to that stress. If you have two bad copies, your brain ages quickly.”

The researchers found a second variant—inside the progranulin gene—that contributes to brain aging, though less so than TMEM106B. Progranulin and TMEM106B are located on different chromosomes but are involved in the same signaling pathway. Both have also been associated with a rare neurodegenerative disease called frontotemporal dementia.

The study did not address what role the two genetic variants might have in neurodegenerative disease. “We were studying healthy individuals, so it is not about disease, per se,” said Dr. Abeliovich.

“But of course, it’s in healthy tissue that you start to get disease. It appears that if you have these genetic variants, brain aging accelerates and that increases vulnerability to brain disease. And vice versa: if you have brain disease, the disease accelerates brain aging. It’s a vicious cycle.”

The study is titled, “Genetic determinants of aging in human brain.”

The study was supported by grants from the National Institute of Aging (AG042317), the National Institute of Neurological Disorders and Stroke, and the Michael J. Fox Foundation for Parkinson's Research.

Dr. Abeliovich is a co-founder of and consultant for Alector. Dr. Rhinn is a consultant for Alector. The researchers declare no other financial conflicts of interest.

Age Not a Factor in Success of Shoulder Replacement Surgery

Newswise, March 20, 2017– Whether you’re younger than 65 or older than 75, age may not be a discernible factor in the success of shoulder replacement surgery, according to a Henry Ford Hospital study.

In a small prospective study of 365 patients, researchers made a surprising finding: While younger patients had better function and range of motion before surgery, it was the older cohort that saw greater improvement from pre-operative levels after surgery. Younger patients also had a higher complication rate.

Researchers theorize that the older patients had greater improvement simply because they had worse shoulder function before surgery.

The study is being presented at the American Academy of Orthopaedic Surgeons annual meeting in San Diego.

“Much like we saw with hip and knee replacements, we are seeing an increased trend in shoulder replacement surgery,” says Kelechi Okoroha, M.D., a fifth-year resident in Henry Ford’s Department of Orthopedic Surgery and the study’s lead author.

“Our study suggests that age is not a noticeable factor on the final outcome of surgery. However, older patients see more improvement in their shoulder function than what they had prior to surgery.”

An estimated 53,000 people undergo shoulder replacement surgery each year due in large part to the “wear and tear” type of arthritis called osteoarthritis. People who have surgery experience an improved quality of life including less pain, improved motion and strength, and function.

Researchers at Henry Ford in Detroit analyzed data and shoulder function scores from two patient cohorts with osteoarthritis who had surgery: 262 patients under 65 and 103 patients older than 75. Patients older than 75 showed greater improvement in shoulder function scores after surgery.

The study was funded by Henry Ford Hospital.

Many Chronically Ill Patients Choose Needlessly Expensive Insurance Plans, Driving Up Medical Costs, According to Johns Hopkins University Researcher

Newswise, March 20, 2017 — Chronic illnesses account for 75 percent of health care expenditures in the United States, and while many cases could be treated with preventive care, a significant number of consumers choose more expensive “curative” options that needlessly drive up medical costs, according to a new study by a Johns Hopkins Carey Business School researcher.

The paper in Marketing Science by Carey Business School Associate Professor Jian Ni proposes a remedy that could guide chronic-illness patients to the appropriate level of care and thus reduce the costs to them and health insurers, helping to lower the nation’s ballooning health care bills.

Ni and his co-authors say their paper breaks new ground on this topic by mining a broader data set than was available to previous researchers, enabling a more detailed view of consumers’ health plan decisions over multiple years.

They had access to three years of detailed data from an unnamed health insurer that offered Preferred Provider Organization plans ― basic, medium, and comprehensive ― to customers through their employers.

Going from basic to medium to comprehensive, the annual premium increased, but the deductible, co-insurance rate (the percentage of expenses the consumer owes after paying the deductible), and out-of-pocket maximum decreased.

The researchers focused on the nearly 3,000 chronic-illness sufferers who bought individual care plans during the 2005-2007 period covered in the study.

Some 133 million Americans are afflicted with chronic maladies, the most common of which include heart disease, cancer, hypertension, respiratory diseases, diabetes, Alzheimer’s disease, and kidney disease.

Preventive care for such illnesses would include diagnostic tests and drugs that keep the patient’s condition from worsening. Curative care would include surgeries and drugs that, while expensive, provide a major boost to the patient’s health. 

In the study, Ni and his colleagues found that about 14 percent of the people who would have been a good match for a medium plan and preventive care ― that is, they were in moderate health, though they felt uncertain about their health status, and price wouldn’t likely be a factor in their purchasing decisions ― nonetheless chose the more costly comprehensive plans and curative care.

As Ni notes, this is a classic example of a “moral hazard,” when a risk taker is largely unaffected by the consequences of the action. In this instance, a health care consumer doesn’t mind choosing a more costly care plan, however unnecessary, because he knows that the insurer will pay for the bulk of it.

“Certainly some people with more serious conditions will benefit from a comprehensive plan and curative care, but the 14 percent in our study pose the kind of moral hazard that contributes to health care expenses in the U.S. that are higher than they probably should be, roughly a fifth of gross domestic product,” Ni, an expert on the impact of consumer behavior on firm strategies, said in an interview.

Giving customers better information could go a long way toward easing the problem, the paper suggests. With clearer instruction and guidance from their physicians and insurers, consumers could develop the habit of choosing plans that would more properly fit their health status. The moral hazard would be mitigated, and the costs to customers and insurers alike trimmed.

The paper, “A Dynamic Model of Health Insurance Choices and Health Care Consumption Decisions,” was derived from Ni’s doctoral dissertation. His co-authors are Professor Kannan Srinivasan of Carnegie Mellon University, Professor Baohong Sun of the Cheung Kong Graduate School of Business, and Associate Professor Nitin Mehta of the University of Toronto.

“Ryancare” Dead on Arrival: Can We Please Now Try Single Payer?

BY ELLEN BROWN/WEB OF DEBT

The Canadian plan also helps Canadians live longer and healthier than Americans. . . . We need, as a nation, to reexamine the single-payer plan, as many individual states are doing.  

— Donald Trump, The America We Deserve (2000)

The new American Health Care Act has been unveiled, and critics are calling it more flawed even than the Obamacare it was meant to replace. Dubbed “Ryancare” or “Trumpcare” (over the objection of White House staff), the Republican health care bill is under attack from left and right, with even conservative leaders calling it “Obamacare Lite”, “bad policy”, a “warmed-over substitute,” and “dead on arrival.”

The problem for both administrations is that they have been trying to fund a bloated, inefficient, and overpriced medical system with scarce taxpayer funds, without capping its costs. US healthcare costs in 2016 averaged $10,345 per person, for a total of $3.35 trillion dollars, a full 18 percent of the entire economy, twice as much as in other industrialized countries.

Ross Perot, who ran for president in 1992, had the right idea: he said all we have to do is to look at other countries that have better health care at lower cost and copy them.

So which industrialized countries do it better than the US? The answer is, all of them.

So which industrialized countries do it better than the US? The answer is, all of them.They all not only provide healthcare for the entire population at about half the cost, but they get better health outcomes than in the US. Their citizens have longer lifespans, fewer infant mortalities and less chronic disease.

President Trump, who is all about getting the most bang for the buck, should love that.

Hard to Argue with Success

The secret to the success of these more efficient systems is that they control medical costs. According to T. R. Reid in The Healing of America, they follow one of three models: the “Bismarck model” established in Germany, in which health providers and insurers are private but insurers are not allowed to make a profit; the “Beveridge model” adopted in Britain, where most healthcare providers work as government employees and the government acts as the single payer for all health services; and the Canadian model, a single-payer system in which the healthcare providers are mostly private.

A single government payer can negotiate much lower drug prices – about half what we pay in the US – and lower hospital prices. Single-payer is also much easier to administer. Cutting out the paperwork can save 30 percent on the cost of insurance.According to a May 2016 post by Physicians for a National Health Program:

Per capita, the U.S. spends three times as much for health care as the U.K., whose taxpayer-funded National Health Service provides health care to citizens without additional charges or co-pays. In 2013, U.S. taxpayers footed the bill for 64.3 percent of U.S. health care — about $1.9 trillion. Yet in the U.S. nearly 30 million of our citizens still lack any form of insurance coverage.

The for-profit U.S. health care system is corrupt, dysfunctional and deadly. In Canada, only 1.5 percent of health care costs are devoted to administration of its single-payer system. In the U.S., 31 percent of health care expenditures flow to the private insurance industry. Americans pay far more for prescription drugs. Last year, CNN reported, Americans paid nearly 10 times as much for prescription Nexium as it cost in the Netherlands.

Single payer, or Medicare for All, is the system proposed in 2016 by Democratic candidate Bernie Sanders. It is also the system endorsed by Donald Trump in his bookThe America We Deserve. Mr. Trump confirmed his admiration for that approach in January 2015, when he said on David Letterman:

A friend of mine was in Scotland recently. He got very, very sick. They took him by ambulance and he was there for four days. He was really in trouble, and they released him and he said, ‘Where do I pay?’ And they said, ‘There’s no charge.’ Not only that, he said it was like great doctors, great care. I mean we could have a great system in this country.

Contrary to the claims of its opponents, the single-payer plan of Bernie Sanders would not have been unaffordable. Rather, according to research by University of Massachusetts Amherst Professor Gerald Friedman, it would have generated substantial savings for the government:

Under the single-payer system envisioned by “The Expanded & Improved Medicare For All Act” (H.R. 676), the U.S. could save $592 billion – $476 billion by eliminating administrative waste associated with the private insurance industry and $116 billion by reducing drug prices …

According to OECD health data, in 2013 the British were getting their healthcare for $3,364 per capita annually; the Germans for $4,920; the French for $4,361; and the Japanese for $3,713. The tab for Americans was $9,086, at least double the others. With single-payer at the OECD average of $3,661 and a population of 322 million, we should be able to cover all our healthcare for under $1.2 trillion annually – well under half what we are paying now.

The Problem Is Not Just the High Cost of Insurance

That is true in theory; but governments at all levels in the US already spend $1.6 trillion for healthcare, which goes mainly to Medicare and Medicaid and covers only 17 percent of the population. Where is the discrepancy?

For one thing, Medicare and Medicaid are more expensive than they need to be, because the US government has been prevented from negotiating drug and hospital costs.

In January, a bill put forth by Sen. Sanders to allow the importation of cheaper prescription drugs from Canada was voted down. Sanders is now planning to introducea bill to allow Medicare to negotiate drug prices, for which he is hoping for the support of the president. Trump indicated throughout his presidential campaign that he would support negotiating drug prices; and in January, he said that the pharmaceutical industry is “getting away with murder” because of what it charges the government. As observed by Ronnie Cummins, International Director of the Organic Consumers Association, in February 2017:

. . . [B]ig pharmaceutical companies, for-profit hospitals and health insurers are allowed to jack up their profit margins at will. . . . Simply giving everyone access to Big Pharma’s overpriced drugs, and corporate hospitals’ profit-at-any-cost tests and treatment, will result in little more than soaring healthcare costs, with uninsured and insured alike remaining sick or becoming even sicker.

Besides the unnecessarily high cost of drugs, the US medical system is prone to over-diagnosing and over-treating. The Congressional Budget Office says that up to 30 percent of the health care in the US is unnecessary. We use more medical technologythen in other countries, including more expensive diagnostic equipment. The equipment must be used in order to recoup its costs. Unnecessary testing and treatment can create new health problems, requiring yet more treatment, further driving up medical bills.

Drug companies are driven by profit, and their market is sickness – a market they have little incentive to shrink. There is not much profit to be extracted from quick, effective cures. The money is in the drugs that have to be taken for 30 years, killing us slowly. And they are killing us. Pharmaceutical drugs taken as prescribed are the fourth leading cause of US deaths, after heart disease, cancer and stroke.  

The US is the only industrialized country besides New Zealand that allows drug companies to advertise pharmaceuticals. Big Pharma spends more on lobbying than any other US industry, and it spends more than $5 billion a year on advertising. Lured by drug advertising, 

Americans are popping pills they don’t need, with side effects that are creating problems where none existed before. Americans compose only 5 percent of the world’s population, yet we consume fully 50 percent of Big Pharma’s drugsand 80 percent of the world’s pain pills. We not only take more drugs (measured in grams of active ingredient) than people in most other countries, but we have the highest use of new prescription drugs, which have a 1 in 5 chance of causing serious adverse reactions after they have been approved.

The US death toll from prescription drugs taken as prescribed is now 128,000 per year.As Jon Rappaport observes, with those results Big Pharma should be under criminal investigation. But the legal drug industry has grown too powerful for that. According to Dr. Marcia Angell, former editor in chief of the New England Journal of Medicine, writing in 2002:

The combined profits for the ten drug companies in the Fortune 500 ($35.9 billion) were more than the profits for all the other 490 businesses put together ($33.7 billion). Over the past two decades the pharmaceutical industry has [become] a marketing machine to sell drugs of dubious benefit, [using] its wealth and power to co-opt every institution that might stand in its way, including the US Congress, the FDA, academic medical centers, and the medical profession itself.

It’s Just Good Business

US healthcare costs are projected to grow at 6 percent a year over the next decade. The result could be to bankrupt not only millions of consumers but the entire federal government.

Obamacare has not worked, and Ryancare is not likely to work. As demonstrated in many other industrialized countries, single-payer delivers better health care at half the cost that Americans are paying now.

Winston Churchill is said to have quipped, “You can always count on the Americans to do the right thing after they have tried everything else.” We need to try a thrifty version of Medicare for all, with negotiated prices for drugs, hospitals and diagnostic equipment.

Ellen Brown

Slow the Signs of Aging With Sun Protection

Dermatologist offers advice for spring breakers, staycationers and everyone in between

Newswise, March 13, 2017— As the winter temperatures begin to thaw, many may be dreaming of a sun-drenched spring and summer, and some may be hoping to show off a tan. While these individuals may believe tanning makes them more beautiful, this habit can actually damage their skin in the long run.

“Ultraviolet radiation from the sun and indoor tanning beds not only can increase your risk of skin cancer but also can contribute to skin aging,” says board-certified dermatologist Arianne Shadi Kourosh, MD, MPH, FAAD, director of community health and co-director of the multiethnic skin clinic in the department of dermatology at Massachusetts General Hospital in Boston.

“Moreover, other forms of radiation, such as heat and visible light, can negatively impact the skin, as can pollution, so protecting your skin from the environment can benefit both your health and appearance.”

According to Dr. Kourosh, environmental factors can damage the skin in multiple ways, from UVB rays causing sunburns and uneven pigmentation to UVA and infrared radiation penetrating more deeply into the skin to damage existing collagen and reduce collagen production, resulting in wrinkles and sagging skin. Habitual UV exposure can cause blood vessels to become more prominent, causing skin redness, she says, while visible light and pollution can cause uneven skin tone, especially in darker skin types.

“Although there have been some impressive strides in anti-aging treatments, no one product or procedure can completely reverse the long-term effects of poor skin care decisions, and protective measures are the cornerstone of good skin care,” Dr. Kourosh says.

“Fortunately, there are many sunscreen options available to help you protect yourself, including cosmetic products with SPF. The best sunscreen for each person will depend on many factors, including genetic makeup, environment and lifestyle considerations.

“A board-certified dermatologist can evaluate the unique needs of your skin and help you develop an appropriate sun protection plan.”

Since both types of UV rays can damage the skin, Dr. Kourosh says, it’s important to use a broad-spectrum sunscreen that provides both UVA and UVB protection, with an SPF of 30 or higher.

She recommends sunscreens containing the active ingredients zinc oxide or titanium dioxide as a good source of broad-spectrum protection suitable for sensitive skin. She also says formulations containing antioxidants may provide some protection against uneven skin tone and aging caused by free radical damage from infrared light, visible light and pollution.

Dr. Kourosh recommends utilizing protective clothing like hats and sunglasses, and she reminds those who will be spending an extended amount of time in the sun to reapply sunscreen every two hours, or after swimming or sweating.

While it’s especially important to be vigilant near sand, water and snow, which can reflect the sun’s rays, sun protection is necessary regardless of weather or location, as 80 percent of the sun’s UV rays can penetrate the skin even on cloudy days.

In addition to practicing sun protection, it’s important to avoid indoor tanning, which exposes users to harmful UV rays that can increase skin cancer risk and accelerate skin aging.

Those who wish to look tan may want to consider a self-tanning product but should continue using sunscreen with it.

“Whether you’re on a beach vacation or your daily commute, it’s crucial to protect yourself from exposure to harmful UV rays on a regular basis,” Dr. Kourosh says.

“If you want healthy, younger-looking skin, it’s better to prevent now than try to correct later. If you have questions about sun protection, talk to a board-certified dermatologist.”

Rapid Blood Pressure Drops in Middle Age Linked to Dementia in Old Age

Temporary episodes of dizziness or light-headedness when standing could reduce blood flow to the brain with lasting impacts

Newswise, March 13, 2017 — Middle-aged people who experience temporary blood pressure drops that often cause dizziness upon standing up may be at an increased risk of developing cognitive decline and dementia 20 years later, new Johns Hopkins Bloomberg School of Public Health research suggests.

The findings, being presented March 10 at the American Heart Association’s EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Ore., suggest that these temporary episodes – known as orthostatic hypotension – may cause lasting damage, possibly because they reduce needed blood flow to the brain. 

Previous research has suggested a connection between orthostatic hypotension and cognitive decline in older people, but this appears to be the first to look at long-term associations.

“Even though these episodes are fleeting, they may have impacts that are long lasting,” says study leader Andreea Rawlings, PhD, MS, a post-doctoral researcher in the Department of Epidemiology at the Bloomberg School. 

“We found that those people who suffered from orthostatic hypotension in middle age were 40 percent more likely to develop dementia than those who did not. It’s a significant finding and we need to better understand just what is happening.”

An estimated four million to five million Americans currently have dementia and, as the population ages, that number is only expected to grow. There currently is no treatment and no cure for the condition.

For the study, the researchers analyzed data from the Atherosclerosis Risk in Communities (ARIC) cohort, a study of 15,792 residents in four communities in the United States, who were between the ages of 45 and 64 when the study began in 1987. For this study, they focused on the 11,503 participants at visit one who had no history of coronary heart disease or stroke. 

After 20 minutes lying down, researchers took the participants’ blood pressure upon standing. Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure. Roughly six percent of participants, or 703 people, met the definition.

These participants, who were on average 54 years old upon enrolling in the study, continued to be followed over the next 20 or more years. People with orthostatic hypotension at the first visit were 40 percent more likely to develop dementia than those who did not have it. They had 15 percent more cognitive decline.

Rawlings says it is not possible to tease out for certain whether the orthostatic hypotension was an indicator of some other underlying disease or whether the drop in blood pressure itself is the cause, though it is likely that the reduction in blood flow to the brain, however temporary, could have lasting consequences.

It also wasn’t clear, she says, whether these participants had repeated problems with orthostatic hypotension over many years or whether they had just a brief episode of orthostatic hypotension at the original enrollment visit, as patients were not retested over time.

“Identifying risk factors for cognitive decline and dementia is important for understanding disease progression, and being able to identify those most at risk gives us possible strategies for prevention and intervention,” Rawlings says. “This is one of those factors worth more investigation.”

“Orthostatic Hypotension is Associated with 20-year Cognitive Decline and Incident Dementia: The Atherosclerosis Risk in Communities (ARIC) Study” was written by Andreea Rawlings; Stephen Juraschek; Gerardo Heiss; Tim Hughes; Michelle Meyer; Elizabeth Selvin; Richey Sharrett; Gwen Windham; and Rebecca Gottesman.

The research was supported by grants from the National Institutes of Health’s National Heart, Lung, and Blood Institute (T32 HL007024) and the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (K24DK106414 and R01DK089174). The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C) with additional funding from the National Institute of Neurological Disorders and Stroke.

Survivors' Bell Gives Cancer Patients Extra Ring of Hope

Left to Right: Ruth Samuels, Infusion MA; patient Becky McIntyre-Velasquez, who donated the bells; Dr. Nimit Sudan, director, medical oncology, Santa Clarita community practice; Teresa de Bree, Infusion Nurse; Tricia P. Eugenio, RN, BSN, OCN, Oncology Nurse Navigator; and Cristelle Dederer, Nursing Supervisor.

Newswise, March 9, 2017 — A large silver bell hangs on a wooden plaque at the entrance of City of Hope | Antelope Valley’s chemotherapy infusion area.

To many, the bell is just hanging décor in the community clinic, but for cancer patients undergoing chemotherapy, it represents much more than that.

The ringing of the bell signifies the end of active treatment and the beginning of a new path.

The bell was donated by 52-year-old Antelope Valley resident Maria “Becky” Velazquez-McIntyre. She was the first patient to ring the bell on July 9, 2015, when she completed treatment for ovarian cancer. Since then 70 more patients in Antelope Valley have done the same.

A bell hanging in City of Hope’s main Duarte campus has been rung by more than 200 patients since it was donated by Velazquez-McIntyre two summers ago.

And now Velazquez-McIntyre is taking the survivor bell ritual to the rest of the 13 City of Hope community practice sites.

“The bell represents hope and a sense of accomplishment,” said Velazquez-McIntyre. “My goal is to give someone else going through chemotherapy that hope. If I can ring that bell, so can you.”

The gift of the bell was inspired by a similar gift from a naval officer treated at a different institution for head and neck cancer some years ago.

 During his time with the Navy, officers would ring a bell to signal the end of a mission, so the officer decided to bring that tradition to his own hospital so patients like himself could celebrate a mission accomplished

.
Velazquez-McIntyre brought the tradition to City of Hope, not only as a thank you to her doctors and the staff who cared for her, but to encourage other cancer patients. She dedicated the bell to her father, who passed away from colon cancer.

Velazquez-McIntyre is an inspiration not only to other patients, but also to City of Hope employees.

“Seeing patients ring the bell is really inspiring and encouraging not only for patients, but for their family members and friends,” said Terri Gore, senior manager of physician relations in Antelope Valley. “Becky represents the core of what City of Hope stands for and that’s the delivery of compassion for everyone.”

New Spiritual Care Communication Board Helps ICU Patients Express Spiritual Needs

The invention improves spiritual care and can reduce anxiety in ventilated intensive care patients

Newswise, March 9, 2017+ – A new spiritual care communication board is helping patients in the intensive care unit (ICU) communicate their emotional and spiritual needs.

The board, created by the Pastoral Care & Education Department at NewYork-Presbyterian/Columbia University Medical Center, is now available to hospitals and healthcare systems across the country.

“Spiritual care in the ICU is often focused on the family members of unconscious, dying patients, and patients who cannot talk either get no spiritual care or only whatever spiritual care other people assume they would want,” said Joel Nightingale Berning, a chaplain at NewYork-Presbyterian and creator of the spiritual care board.

“The spiritual care board allows more patient-centered chaplaincy. The patients guide the spiritual support they truly want and need to cope with some of the most difficult experiences of their lives.”

The board displays words and illustrations that allow mechanically ventilated patients to indicate their preferences for spiritual care.

 Working with a chaplain, patients point to the words or illustrations that indicate their spiritual or religious affiliation, emotional state, spiritual needs and desired chaplain intervention.

The overall purpose of the board is to reduce anxiety in patients and ensure they receive the most appropriate spiritual care.

Traditional communication boards have been used for more than a decade to help medical personnel obtain critical information from non-vocal patients who are in one of the many phases of ICU care.

The boards allow patients who are alert but cannot speak to indicate a number of needs during their stay by pointing to letters, words or pictures in a variety of formats and languages.

These clinical communication boards provide immediate feedback from the patient to the care team, providing more effective and focused care, while reducing the communications issues that can sub-optimize the ICU experience.

While these clinical communication tools have played an extensive role in improving patient experience, they had never before been used for spiritual care.

A recent study in the Annals of the American Thoracic Society (AnnalsATS) led by Chaplain Berning and Dr. Matthew R. Baldwin, attending physician in Critical Care Services at NewYork-Presbyterian/Columbia University Medical Center and assistant professor of medicine at Columbia University Medical Center, found that patients in NewYork-Presbyterian’s ICUs were able to complete the card with a chaplain’s assistance and receive a desired spiritual care intervention in a median time of 18 minutes.

Patients reported a mean 31 percent immediate reduction in anxiety after receiving this care for the first time, and those who survived intensive care reported a reduction in stress that they attributed to picture-guided spiritual care.

The study authors indicate that more research on communication and psychoemotional suffering for patients in the ICU setting is needed, however using this unique spiritual assessment tool with ICU patients opens a novel area of chaplaincy and palliative care clinical research.

The AnnalsATS also published an editorial saying that the spiritual care board “may also open the door to targeted psychoemotional assessments and interventions previously ignored or deemed ‘inappropriate’ due to communication barriers.”

“We heard from many patients that acknowledging their emotions with a chaplain was crucial in helping them cope with their critical illness,” said Dr. Baldwin.

“We hope that with greater access to this tool, more patients will be able to express their spiritual needs in an effort to ease the emotional toll an ICU stay has.”

In accordance with established criteria of the Association of Professional Chaplains’ Standards of Practice as well as the authors’ clinical experience, NewYork-Presbyterian’s NYP Ventures arm has worked with Vidatak/Acuity Medical to produce the card in English and Spanish for hospital distribution across the U.S.

Scientists Identify Chain Reaction That Shields Breast Cancer Stem Cells From Chemotherapy

Newswise, March 9, 2017 — Working with human breast cancer cells and mice, researchers at Johns Hopkins say they have identified a biochemical pathway that triggers the regrowth of breast cancer stem cells after chemotherapy.

The regrowth of cancer stem cells is responsible for the drug resistance that develops in many breast tumors and the reason that for many patients, the benefits of chemo are short-lived. Cancer recurrence after chemotherapy is frequently fatal.

"Breast cancer stem cells pose a serious problem for therapy," says lead study investigator Gregg Semenza, M.D., Ph.D., the C. Michael Armstrong Professor of Medicine, director of the Vascular Biology Program at the Johns Hopkins Institute for Cell Engineering and a member of the Johns Hopkins Kimmel Cancer Center.

"These are the cells that can break away from a tumor and metastasize; these are the cells you most want to kill with chemotherapy. Paradoxically, though, cancer stem cells are quite resistant to chemotherapy."

Semenza says previous studies have shown that resistance to chemotherapy arises from the hardy nature of cancer stem cells, which are often found in the centers of tumors, where oxygen levels are quite low.

Their survival is made possible through proteins known as hypoxia-inducible factors (HIFs), which turn on genes that help the cells survive in a low-oxygen environment.

In this new study, described Feb. 21 in Cell Reports, Semenza and his colleagues conducted gene expression analysis of multiple human breast cancer cell lines grown in the laboratory after exposure to chemotherapy drugs, like carboplatin, which stops tumor growth by damaging cancer cell DNA.

The team found that the cancer cells that survived tended to have higher levels of a protein known as glutathione-S-transferase O1, or GSTO1. Experiments showed that HIFs controlled the production of GSTO1 in breast cancer cells when they were exposed to chemotherapy; if HIF activity was blocked in these lab-grown cells, GSTO1 was not produced.

Semenza notes that GSTO1 and related GST proteins are antioxidant enzymes, but GSTO1's role in chemotherapy resistance did not require its antioxidant activity.

 Instead, following exposure to chemotherapy, GSTO1 binds to a protein called the ryanodine receptor 1, or RYR1, that triggers the release of calcium, which causes a chain reaction that transforms ordinary breast cancer cells into cancer stem cells.

To more directly assess the role of GSTO1 and RYR1 in the breast tumor response to chemotherapy, the researchers injected human breast cancer cells into the mammary gland of mice and then treated the mice with carboplatin after tumors had formed. In addition to using normal breast cancer cells in the experiments, the team also used cancer cells that had been genetically engineered to lack either GSTO1 or RYR1.

Loss of either GSTO1 or RYR1, the researchers report, decreased the number of cancer stem cells in the primary tumor, blocked metastasis of cancer cells from the primary tumor to the lungs, decreased the duration of chemotherapy required to induce remission and increased the duration of time after chemotherapy was stopped that the mice remained tumor-free.

Although the study showed that blocking the production of GSTO1 may improve the efficacy of chemotherapy drugs, such as carboplatin, GSTO1 is only one of many proteins that are produced under the control of HIFs in breast cancer cells that have been exposed to chemotherapy.

The Semenza lab is working to develop drugs that can block the action of HIFs, with the hope that HIF inhibitors will make chemotherapy more effective.

Other authors of the report include Haquin Li, Ivan Chen, Larissa Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran and Huimin Zhang of the Johns Hopkins University School of Medicine.

This work was supported by an Impact Award from the Department of Defense (grant number W81XWH-12-1-0464) and a Research Professor Award from the American Cancer Society.

Popular Heartburn Drugs Linked to Gradual Yet ‘Silent’ Kidney Damage

Most patients don't experience acute kidney problems beforehand

Newswise, March 9, 2017 — Taking popular heartburn drugs for prolonged periods has been linked to serious kidney problems, including kidney failure. The sudden onset of kidney problems often serves as a red flag for doctors to discontinue their patients’ use of so-called proton pump inhibitors (PPIs), which are sold under the brand names Prevacid, Prilosec, Nexium and Protonix, among others.

But a new study evaluating the use of PPIs in 125,000 patients indicates that more than half of patients who develop chronic kidney damage while taking the drugs don’t experience acute kidney problems beforehand, meaning patients may not be aware of a decline in kidney function, according to researchers at Washington University School of Medicine in St. Louis and the Veterans Affairs St. Louis Health Care System.

Therefore, people who take PPIs, and their doctors, should be more vigilant in monitoring use of these medications.

The study is published   in Kidney International.

“The onset of acute kidney problems is not a reliable warning sign for clinicians to detect a decline in kidney function among patients taking proton pump inhibitors,” said Ziyad Al-Aly, MD, the study’s senior author and an assistant professor of medicine at Washington University School of Medicine.

 “Our results indicate kidney problems can develop silently and gradually over time, eroding kidney function and leading to long-term kidney damage or even renal failure. Patients should be cautioned to tell their doctors if they’re taking PPIs and only use the drugs when necessary.”

More than 15 million Americans suffering from heartburn, ulcers and acid reflux have prescriptions for PPIs, which bring relief by reducing gastric acid. Many millions more purchase the drugs over-the-counter and take them without being under a doctor’s care.

The researchers — including first author Yan Xie, a biostatistician at the St. Louis VA —analyzed data from the Department of Veterans Affairs databases on 125,596 new users of PPIs and 18,436 new users of other heartburn drugs referred to as H2 blockers. The latter are much less likely to cause kidney problems but often aren’t as effective.

Over five years of follow up, the researchers found that more than 80 percent of PPI users did not develop acute kidney problems, which often are reversible and are characterized by too little urine leaving the body, fatigue and swelling in the legs and ankles.

However, more than half of the cases of chronic kidney damage and end-stage renal disease associated with PPI use occurred in people without acute kidney problems.

In contrast, among new users of H2 blockers, 7.67 percent developed chronic kidney disease in the absence of acute kidney problems, and 1.27 percent developed end-stage renal disease.

End-stage renal disease occurs when the kidneys can no longer effectively remove waste from the body. In such cases, dialysis or a kidney transplant is needed to keep patients alive.

“Doctors must pay careful attention to kidney function in their patients who use PPIs, even when there are no signs of problems,” cautioned Al-Aly, who also is the VA’s associate chief of staff for research and education and co-director of the VA’s Clinical Epidemiology Center.

 “In general, we always advise clinicians to evaluate whether PPI use is medically necessary in the first place because the drugs carry significant risks, including a deterioration of kidney function.”

Anti-Aging Gene Identified as a Novel Promising Therapeutic Target for Older Melanoma Patients

Pharmacologic activation of anti-aging gene with anti-diabetic drug could be used as adjuvant therapy for older melanoma patients who have developed resistance to targeted therapy

Newswise, March 9, 2017— Scientists at The Wistar Institute have shown that an anti-diabetic drug can inhibit the growth of melanoma in older patients by activating an anti-aging gene that in turn inhibits a protein involved in metastatic progression and resistance to targeted therapies for the disease. 

The study was published online in Clinical Cancer Research.

Even more than other types of cancer, melanoma is a disease of aging, with older patients more frequently diagnosed with the disease and having a worse prognosis. 

Targeted therapies have brought benefits in terms of overall survival compared to chemotherapy but they are limited by intrinsic or acquired resistance. Wistar scientists have previously shown that age-related changes in the tumor microenvironment — or the surrounding area where tumor cells crosstalk with normal and immune cells — can drive melanoma progression and therapy resistance. 

They have also discovered that a protein named Wnt5A promotes metastatic progression, resistance to therapy and poorer prognosis, and one of the ways in which it is regulated is by the anti-aging protein Klotho. 

The new study shows that treating mice with a drug that promotes Klotho expression reduces the levels of Wnt5A and decreases the growth of therapy-resistant melanoma in aged mice but, importantly, not in young mice.

“We have already shown that age-related changes in the tumor microenvironment are accountable for the higher metastatic potential of melanoma in older patients,” said Ashani Weeraratna, Ph.D., Ira Brind Associate Professor and program leader of the Tumor Microenvironment and Metastasis Program at Wistar and lead author of the paper. 

“Our new study indicates that a differential therapeutic approach can be beneficial for older patients in melanoma and suggests that age should be taken into account to design better treatments for certain cohorts of patients.”

Weeraratna’s team used an artificial skin reconstruct model to recreate the interactions of melanoma cells with either a young or aged tumor microenvironment. 

They observed an intricate reciprocal regulation between Klotho, Wnt5A, melanoma cells, and the tumor microenvironment. 

They also showed that they could manipulate Klotho expression pharmacologically using the anti-diabetic drug rosiglitazone, which resulted in decreased levels of Wnt5A. Importantly, while using rosiglitazone in conjunction with targeted therapy reduced tumor growth in both young and aged pre-clinical models, using rosiglitazone alone accelerated tumor growth in young models, while inhibiting it in aged ones.

“We believe that there is a threshold effect whereby the levels of Klotho, dictated mostly by the age of the patients, are crucial in determining whether they will benefit from this treatment or not,” said Reeti Behera, Ph.D., a postdoctoral researcher in the Weeraratna lab and first author of the study. 

“Previous studies had tested the use of rosiglitazone for cancer treatment, but the outcome was not encouraging. I think they may have been missing a piece of the puzzle, by not considering aging and the tumor microenvironment.”

This research lays the foundation for the development of promising adjuvant therapy for older melanoma patients. More studies will be needed to confirm the benefits in human subjects. Klotho is a secreted protein that can be measured in the serum of patients and this can help in determining which patients would benefit from rosiglitazone therapy and would be eligible for further studies.

This work was supported by National Institutes of Health grants RO1 CA174746-01, P01 CA 114046-06, T32 CA 9171-36, P50 CA174523-01and R01-CA1826635; grants from the Melanoma Research Foundation, the American Cancer Society, and the Miriam and Sheldon Adelson Research Foundation. Weeraratna is supported by the Ira Brind Associate Professorship. Core support for The Wistar Institute was provided by the Cancer Center Support Grant CA010815.

Co-authors of this study from The Wistar Institute include: Amanpreet Kaur, Marie R. Webster, Suyeon Kim, Abibatou Ndoye, Curtis H. Kugel III, Gretchen M. Alicea, Joshua Wang, Sofia Lisanti, Katie Marchbank, Vanessa Dang, Kanad Ghosh, Meenhard Herlyn, Cecilia Caino, and Dario C. Altieri. Other co-authors include: Phil Cheng, Mitchell Levesque, and Reinhard Dummer from University of Zurich, Switzerland; Xiaowei Xu from University of Pennsylvania; Andrew E. Aplin from Thomas Jefferson University; and Alexander Roesch from University Duesburg-Essen, Essen, Germany.

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The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the United States, Wistar has held the prestigious Cancer Center designation from the National Cancer Institute since 1972. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. wistar.org.