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Sugar control and regular eye exams are your best defense

By David Dunaief, M.D.

Dr. David Dunaief

We talk a lot in the medical community about the vascular consequences of diabetes, and rightly so. If you have diabetes, you are at high risk of vascular complications that can be life-altering. Among these are macrovascular complications, like coronary artery disease and stroke, and microvascular effects, such as diabetic nephropathy and retinopathy.

Here, we will discuss diabetic retinopathy (DR), the number one cause of blindness among U.S. adults, ages 20 to 74 years old (1). Diabetic retinopathy (DR) is when the blood vessels that feed the light-sensitive tissue at the back of your eye are damaged, and it can progress to blurred vision and blindness.

As of 2019, only about 60 percent of people with diabetes had a recommended annual screening for DR (2). Why does this matter? Because the earlier you catch it, the more likely you will be able to prevent or limit permanent vision loss.

Over time, DR can lead to diabetic macular edema (DME). Its signature is swelling caused by fluid accumulating in the macula (3). An oval spot in the central portion of the retina, the macula is sensitive to light. When fluid builds up from leaking blood vessels, it can cause vision loss.

Those with the longest duration of diabetes have the greatest risk of DME. Unfortunately, many patients are diagnosed with DME after it has already caused vision loss. If not treated early, patients can experience permanent damage (2).

In a cross-sectional study using NHANES data, among patients with DME, only 45 percent were told by a physician that diabetes had affected their eyes (4). Approximately 46 percent of patients reported that they had not been to a diabetic nurse educator, nutritionist or dietician in more than a year — or never.

Unfortunately, the symptoms of vision loss don’t necessarily occur until the latter stages of the disorder, often after it’s too late to reverse the damage.

Treatment options

While DME has traditionally been treated with lasers, injections of anti-VEGF medications may be more effective. These eye injections work by inhibiting overproduction of a protein called vascular endothelial growth factor (VEGF), which contributes to DR and DME (5).

The results from a randomized controlled trial showed that eye injections with ranibizumab (Lucentis) in conjunction with laser treatments, whether laser treatments were given promptly or delayed for at least 24 weeks, were equally effective in treating DME (6). Other anti-VEGF drugs include aflibercept (Eylea) and bevacizumab (Avastin).

Risk from diabetes treatments

You would think that using medications to treat type 2 diabetes would prevent DME from occurring as well. However, in the THIN trial, a retrospective study, a class of diabetes drugs, thiazolidinediones, which includes Avandia and Actos, actually increased the occurrence of DME compared to those who did not use these oral medications (7). Those receiving these drugs had a 1.3 percent incidence of DME at year one, whereas those who did not had a 0.2 percent incidence. This incidence was persistent through the 10 years of follow-up. Note that DME is not the only side effect of these drugs. There are important FDA warnings for other significant issues.

To make matters worse, those who received both thiazolidinediones and insulin had an even greater incidence of DME. There were 103,000 diabetes patients reviewed in this trial. It was unclear whether the drugs, because they were second-line treatments, or the severity of the diabetes itself may have caused these findings.

This is in contrast to a previous ACCORD eye sub-study, a cross-sectional analysis, which did not show an association between thiazolidinediones and DME (8). This study involved review of 3,473 participants who had photographs taken of the fundus (the back of the eye).

What does this ultimately mean? Both studies had weaknesses. It was not clear how long the patients had been using the thiazolidinediones in either study or whether their sugars were controlled and to what degree. The researchers were also unable to control for all other possible confounding factors (9). There are additional studies underway to clarify these results.

Glucose control and diet

The risk of progression of diabetic retinopathy was significantly lower with intensive blood sugar controls using medications, one of the few positive highlights of the ACCORD trial (10). Unfortunately, medication-induced intensive blood sugar control also resulted in increased mortality and no significant change in cardiovascular events. However, an inference can be made: a nutrient-dense, plant-based diet that intensively controls blood sugar is likely to decrease the risk of diabetic retinopathy and further vision complications (11, 12).

If you have diabetes, the best way to avoid diabetic retinopathy and DME is to maintain good control of your sugars. Also, it is imperative that you have a yearly eye exam by an ophthalmologist so that diabetic retinopathy is detected as early as possible, before permanent vision loss occurs. If you are taking the oral diabetes class thiazolidinediones, this is especially important.

References: 

(1) cdc.gov. (2) www.aao.org/ppp. (3) www.uptodate.com. (4) JAMA Ophthalmol. 2014;132:168-173. (5) Community Eye Health. 2014; 27(87): 44–46. (6) ASRS. Presented 2014 Aug. 11. (7) Arch Intern Med. 2012;172:1005-1011. (8) Arch Ophthalmol. 2010 March;128:312-318. (9) Arch Intern Med. 2012;172:1011-1013. (10) www.nei.nih.gov. (11) OJPM. 2012;2:364-371. (12) Am J Clin Nutr. 2009;89:1588S-1596S.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

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Pumpkin Loaf

By Heidi Sutton

Pumpkins are a quintessential Halloween ingredient, but these recipes for breakfast, dinner and dessert are so good, you may be tempted to have them year round.

Pumpkin Pancakes

YIELD: Makes 4 to 6 servings

INGREDIENTS: 

2 1/2 cups flour

1/4 cup sugar

1 tablespoon baking powder

2 teaspoons ground cinnamon 

1 teaspoon salt

3/4 teaspoon ground cloves 

3/4 teaspoon ground ginger 

1/4 teaspoon ground allspice 

2 cups milk

3 large eggs

1 15-ounce can pumpkin puree

DIRECTIONS:

Whisk the flour, sugar, baking powder, cinnamon, salt, cloves, ginger and allspice together in a large bowl. In another bowl, whisk the milk, eggs and pumpkin puree. Add the wet ingredients to the dry and stir until the ingredients are just mixed. Let rest for five minutes. Heat a griddle or nonstick skillet over medium heat. Ladle a 1⁄2 cup of batter onto the skillet and cook until the pancakes are golden on the bottom and bubbly on top, about 2 minutes. Flip and cook until the second side is golden brown and the pancake is cooked through. Serve with maple syrup.

Pumpkin Chili

YIELD: Makes 6 to 8 servings

INGREDIENTS: 

2 tablespoons olive oil

1 medium onion, chopped

1 medium yellow bell pepper, chopped

3 garlic cloves, minced

2 15-ounce cans black beans, rinsed , drained

1 15-ounce can solid-pack pumpkin

1 14.5-ounce can diced tomatoes, undrained

3 cups chicken broth

2 1/2 cups cubed cooked turkey (optional)

2 teaspoons dried parsley flakes 

2 teaspoons chili powder

1 1/2 teaspoons ground cumin

1 1/2 teaspoons dried oregano 

1/2 teaspoon salt

DIRECTIONS:

In a large skillet over medium-high heat, heat the oil. Add the onion and pepper and cook until tender. Add the garlic and cook one minute longer. Transfer to a five-quart slow cooker and stir in the next 10 ingredients. Cook on low for 4-5 hours. Serve hot.

Pumpkin Loaf

YIELD: Makes 1 loaf plus 12 muffins

INGREDIENTS: 

Nonstick cooking spray

4 eggs

3 1/2 cups flour

2 teaspoons baking soda

2 teaspoons cinnamon

1 teaspoon nutmeg

1 teaspoon salt

2 sticks butter

1 cup sugar

1 can (15 ounces) pumpkin puree

1 cup chocolate chips

1 cup walnuts, chopped

DIRECTIONS:

Heat oven to 350 F. Prepare loaf and muffin pans with nonstick cooking spray. In bowl, whisk eggs. Set aside. In separate bowl, sift flour, baking soda, cinnamon, nutmeg and salt together. Set aside. 

In another bowl, cream butter and sugar. Add whisked eggs and mix until blended. Alternately add flour mixture and pumpkin puree to egg mixture, beating until blended. Fold in chocolate chips and walnuts. Pour batter into loaf and muffin pans. Bake 40 to 45 minutes, or until toothpick inserted into center comes out clean. Cool 10 minutes before removing from pans.

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Pixabay photo

By Daniel Dunaief

Daniel Dunaief

My grandmother was a worrier. 

Even she, however, would have had a hard time worrying about other major challenges, problems and threats during the worst of the COVID-19 pandemic.

That, it turns out, was also true for the world during COVID when it came to discussions about the threat from climate change.

In a recent study published in the prestigious journal Proceedings of the National Academy of Sciences, Oleg Smirnov, associate professor in the Department of Political Science at Stony Brook University, examined the level of concern on Twitter about climate change during 2020 and 2021 and compared those numbers to 2019, the last year before COVID.

According to the pool of finite worry, which Princeton professor of Psychology Elke Weber developed, environmental and climate concerns decline amid worries about other major threats.

Smirnov found that the total number of tweets that mention climate change dropped to 5.6 million in 2020 and 5.3 million in 2021, from 8 million in 2019. This, Smirnov points out, occurred despite an increase in Twitter users, more climate disasters and more climate news in 2021.

“The psychological foundation tell us that people may only really respond to one threat at a time,” Smirnov said in an interview. The anxiety and the reaction to that threat may be limited because it requires major energy.

“Maybe, for biological reasons, [people] put all their energy into responding to the most immediate threat,” Smirnov added.

By tracking daily tweets and various measures of COVID cases, Smirnov found on a finer scale as well that discussions of climate change diminished amid higher infections and mortality.

For every thousand new COVID-19 cases in the United States, climate change tweets decreased by about 40.5 tweets per day. Every thousand new deaths resulted in 3,308 fewer climate tweets.

While Smirnov understood the need to focus on the pandemic, he suggested a lack of concern about climate change could disrupt efforts to protect the planet

“This has profound implications,” Smirnov said. “Without a focus on climate change, without an emphasis on its importance, there is less urgency and less pressure on politicians to do something about it.”

Even in better times, climate change efforts are “fragile,” he said, which adds to the uncertainty about the ability to address the challenge adequately.

Indeed, even the sentiment analysis, in which Smirnov reviewed the emotional content of words used to describe climate change and the threat to the planet and humanity, became less negative during the worst of the pandemic.

When asked about the possibility that climate change concerns might have declined during COVID in part because the carbon footprint declined amid travel restrictions and slowdowns in industrial production, Smirnov likened such an approach to short-term fasting or extreme dieting.

While spending a few days on these extreme diets can reduce a person’s weight over the course of days, such an approach provides “no substantial improvement in your health” longer term, he said.

So, what about now, as concerns about the pandemic abate, people have stopped wearing masks and schools and stadiums are full?

Smirnov plans to continue to collect Twitter data for the remainder of this year, to see whether a return to normalcy brings the focus back to the threat from climate change.

As for his own experience, Smirnov recognized that climate change took a back burner amid the worst of the pandemic.

“My attention certainly was hijacked by COVID-19, despite the fact that climate change is part of my work,” Smirnov said. In April of 2020, Smirnov recalled worrying about where his family would find food instead of thinking about greenhouse gases and rising sea levels.

In the present, Smirnov remains concerned about the kind of tipping points and climate inertia that threatens the future.

Ever the worrier, my grandmother might be relieved enough by the less virulent form of the virus and the availability of vaccines and treatment to return to worrying about the threat climate change poses.

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Pixabay photo

By Leah S. Dunaief

Leah Dunaief

It was time to get away, even for a day, and when better than on foliage weekend! So Saturday, we took the ferry to Connecticut and started up Route 8 to get to the Berkshires and the seasonal colors. Were we too late in the fall? Shortly after we left Bridgeport, our choice of time and place were confirmed. It was a perfect autumn day, sunny, bright, soft breeze, balmy even, and the colors burst upon us, the reds, oranges, yellows mixed with a still significant amount of green as we began to drive through the hills. No, we were not too late.

We had been concerned, too, about the effects of the summer’s drought on the leaves. We needn’t have worried. Perhaps, it wasn’t the most dramatic foliage we had ever witnessed, some trees were already bare, but it was brilliant enough to excite our eyes. We whooped around every bend in the road that presented us with a new palette of hills and color. 

The timing of foliage season has altered somewhat over the past few years. Climate change has impacted peak leaf peeping by extending the warmer weather that keeps trees green. Hence the optimal viewing time has also been delayed. This year, according to records, seems like it will clock in as the fifth warmest. So it turned out that our urge for an outing was right on.

Where to go?

The Store

While it was possible just to drive slowly, drinking in the scenery, it was also fun to have a destination in mind. We left the highway, or rather it left us as it ended in Winsted, incidentally, my dad’s birthplace, and we started on a local road that eventually led us to Southfield, the home of a long-ago college roommate with whom we had lost contact. She, and her family, as we discovered, no longer lived there, but that didn’t stop us from enjoying the tiny town. Yes, it was one of those “blink and you will miss it” villages, but we didn’t blink. We parked and had lunch at The Store, a delightful coffee, pastry and sandwich shop with tables inside as well as out front. Happily installed in one corner of the patio with a turkey and avocado sandwich and a generous slice of chocolate-banana bread, to be washed down with ambrosial coffee, we chatted up the couple at the adjoining table, who were smiling at us.

In fact, it was the kind of day that prompted everyone to smile. There we were, amid glorious leafage, basking in ideal temperature and bright sunlight in the peaceful countryside. They told us their names, Paul and Julia, and that they were from Westchester County and celebrating their anniversary. For the first time, they were at leisure to do that because their two children, a son and a daughter, were at college. She was a psychologist, he worked in finance, and they had left their responsibilities behind to stay at the historic inn in the next village for the weekend.

They were fun to talk to, as was every other person who went by, walking their dogs. We asked each one if they knew the roommate’s family, but just about each one apologized and explained that they had only moved there 20 years ago. What a coincidence, we thought. They had all come more or less at the same time. It wasn’t until the next day that we realized what had happened those two decades ago: 9/11 happened. If one wanted to escape from a city to a safe and bucolic place, here was one such location. Perhaps that was what brought them there.

We stayed in the area, driving around, enjoying the typical New England white clapboard church with its distinctive steeple, the inn and the village common along with glorious Nature. Then, as night fell, we had dinner at the inn before returning home.

The next day, I felt as if I had been aired out.

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From left, K. Barry Sharpless and John Moses. Photo from CSHL

By Daniel Dunaief

K. Barry Sharpless changed John Moses’s life. And that’s before Moses even started working as a postdoctoral researcher in Sharpless’s lab.

When Moses, who is the first chemist to work at Cold Spring Harbor Laboratory in its 132-year history, was earning his PhD in chemistry at Oxford, he read an article that Sharpless co-authored that rocked his world.

Nicknamed the “click manifesto” for introducing a new kind of chemistry, the article, which was published in Angewandte Chemie in 2001, was “one of the greatest I’ve ever read,” Moses said, and led him to alter the direction of his research.

Moses walked into the office of the late chemist Sir Jack Baldwin at Oxford, who was Moses’s PhD advisor, and announced that Sharpless, a colleague of Baldwin’s at the Massachusetts Institute of Technology, was the only chemist he wanted to work with in the next phase of his career.

Baldwin looked at Moses and said, in a “very old-fashioned gangster English, ‘That shows you’ve got some brains,’” recalled Moses.

Sharpless was important not only to Moses’s career, but also to the world.

Recently, Sharpless, who is the W.M. Kepp Professor of Chemistry at Scripps Research, became only the fifth two-time recipient of the Nobel Prize.

Sharpless will share the most recent award, which includes a $900,000 prize, with Carolyn R. Bertozzi, the Anne T. and Robert M. Bass Professor in the School of Humanities and Sciences at Stanford University, and Morten P. Meldal, professor at the University of Copenhagen, for the invention of a type of chemistry that has implications and applications from drug discovery and delivery, to making polymers, to developing anti cancer treatments.

The way click chemistry works is that chemists bring together catalysts and reagents, often attached to sulfur or carbon, that have a high level of specific attraction for each other. The click is like the sound a seat belt makes when secured, or the click a bike helmet lock makes when the two units are connected.

Scientists have often described the click reaction as being akin to LEGO blocks coming together, with an exact and durable chemical fit.

Natural product synthesis is generally challenging and often requires complex chemistries that are not always selective. This type of chemistry can produce side reactions that create unwanted byproducts and require purification.

Click reactions, by contrast, are selective and reliable and the products are generally easy to purify. Sometimes, purification is as simple as a water wash.

“It’s a democratization of synthetic chemistry,” Moses said.

Moses said biologists have performed click reactions. Chemists have developed click tablets that can be added to a reaction to create a plug and play system.

Moses described the reactions in click chemistry as “unstoppable” and suggested that they are part of a “domino rally” in which a latent build up of reactivity can create desired products with beneficial properties.

Moses, who arrived at CSHL in 2020, has collaborated with several researchers at the famed lab. He is submitting his first collaborative paper soon with Dr. Michael Lukey, who also started in 2020 and performed his PhD at Oxford, and Dr. Scott Lyons. He is also working on a New York State Biodefense funded project to create shape shifting antibiotics that can keep up with drug resistance pathogens. 

He has collaborated with Cancer Center Director David Tuveson to develop a new ligand to target a protein important in pancreatic cancer. Moses said they have a “very exciting” lead compound.

Early resistance

While the Nobel Prize committee recognized the important contribution of this approach, the concept met with some resistance when Sharpless introduced it.

“When [Sharpless] submitted this, the editor called colleagues and asked, ‘Has Barry gone crazy?’” Moses said.

Some others in the field urged the editor to publish the paper by Sharpless, who had already won a Nobel Prize for his work with chirally catalyzed oxidation reactions.

Still, despite his bona fides and a distinguished career, Sharpless encountered “significant resistance” from some researchers. “People were almost offended by it” with some calling it “old wine in new bottles,” Moses said.

In 2007, Moses attended a faculty interview at a “reasonably good” university in England,. where one of his hosts told him that click chemistry is “just bulls$#t!”

Moses recognized that he was taking a risk when he joined Sharpless’s lab. Some senior faculty advised him to continue to work with natural product synthesis.

In the ensuing years, as click chemistry produced more products, “everyone was using it and the risks diminished quickly,” Moses added.

Unique thought process

So, what is it about Sharpless that distinguishes him?

Moses said Sharpless’s wife Janet Dueser described her husband as someone who “thinks like a molecule,” Moses said.

For Moses, Sharpless developed his understanding of chemistry in a “way that I’ve never seen anyone else” do.

Moses credits Dueser, who he described as “super smart,” with coining the term “click chemistry” and suggested that their partnership has brought together his depth of knowledge with her ability to provide context.

Moses believes Sharpless “would admit that without [Dueser], his career would have been very different! In my opinion, [Dueser] contributed immeasurably to click chemistry in so many ways.”

Indeed, click chemistry won a team prize from the Royal Society of Chemistry last year in which Dueser was a co-recipient.

As for what he learned from working with a now two-time Nobel Prize winner, Moses said “relinquishing control is very powerful.”

Moses tells his research team that he will never say “no” to an innovative idea because, as with click chemistry, “you never know what’s around the corner.”

Moses said Sharpless is a fan of the book “Out of Control” by Kevin Kelly, the co-founder of Wired Magazine. The book is about the new biology of machines, social systems and the economic world. Sharpless calls Kelly “Saint Kevin.”

On a personal level, Sharpless is “humble and a nice person to talk to” and is someone he would “want to go to a pub with.”

Moses believes Sharpless isn’t done contributing to chemistry and the world and anticipates that Sharpless, who is currently 81 years old, could win another Nobel Prize in another 20 years.

An inspirational scientist, Sharpless ” is “that kind of person,” Moses said.

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Zendaya

MEET ZENDAYA!

This week’s shelter pet is Zendaya, a beautiful spayed domestic short hair up for adoption at the Smithtown Animal Shelter. She just turned 1 and is playful, adventurous and a HUGE flirt.   

Zendaya

This stunner has Feline Leukemia, so she will need to be the only cat, placed with other positive cats, or Leukemia vaccinated cats.  

Cats with leukemia typically live a short life, but they are filled with love to give and deserve the happiest homes to make the most of the time that they have.

If you would like to meet Zendaya, please call ahead to schedule an hour to properly interact with her in a domestic setting.

The Smithtown Animal & Adoption Shelter is located at 410 Middle Country Road, Smithtown. Visitor hours are currently Monday to Saturday from 10 a.m. to 3 p.m. (Sundays and Wednesday evenings by appointment only). For more information, call 631-360-7575 or visit www.townofsmithtownanimalshelter.com.

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METRO photo

By Bob Lipinski

Bob Lipinski

Recently I was invited to a friend’s house for dinner and as we enjoyed a few appetizers, he served a bottle of a 1998 Australian Chardonnay from a winery I’ve never heard of. The wine was dark yellow and when tasted, it was well past its point of drinkability.

According to my friend, the wine was stored in his temperature-controlled cellar for over 10 years. He was dismayed to learn that some wines need aging, but the vast majority are best drunk when released for sale by the winery.

I explained that there is no precise answer when a wine will be at its peak because wines age at difference paces. The vintage, growing conditions, winemaking and barrel or stainless-steel aging, also plays a part in wine’s ability to age. The aging curve of wine depends on the location and conditions where the wine will be stored. Also, personal taste plays a significant role in the enjoyment of wine. As an example, many people enjoy champagne when first released with its youthful freshness, while others enjoy the more mature, bottle-aged versions.

Vintage charts and vintage reports, often touted by online sources, will provide you with a ballpark idea when the wine will be at its peak. They often say, “drink by this date or hold until that date.”

Wine’s longevity can be attributed to many factors, among them higher acidity, higher alcohol, carbonation, concentrated fruit, sugar (residual), and tannin, which is an antioxidant.

Not all wines are age-worthy, and in fact, most wines available for sale are not. Wines that benefit from years in the bottle (cellar) tend to be more expensive. I generally purchase several bottles of the same wine and after a few years, open one bottle and see if it’s approaching maturing. Then I decide (with some guesswork) when the next bottle should be opened.

Except for most Chardonnay, Riesling, and sweet wines, white wines should be consumed within three years after the vintage. Most red wines are best between four and seven years after the vintage. Red wines that can age much longer than seven years include Amarone della Valpolicella, Barbaresco, Barolo, Bordeaux, Brunello di Montalcino, Burgundy, Cabernet Sauvignon, and Chianti Classico Riserva.

My rule for aging wine is simple. I’d rather open a bottle of a young wine and say, “It tastes good now but will be better in ‘X’ years” rather than opening a bottle of wine aged for many years and say, “It was probably good several years ago, but now it’s over-the-hill!”

Bob Lipinski is the author of 10 books, including “101: Everything You Need To Know About Whiskey” and “Italian Wine & Cheese Made Simple” (available on Amazon.com). He consults and conducts training seminars on Wine, Spirits, and Food and is available for speaking engagements. He can be reached at www.boblipinski.com OR [email protected].

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Cut down on late night snacking to avoid GERD. METRO photo
Increased fiber and exercise improve symptoms

By David Dunaief, M.D.

Dr. David Dunaief

After a large meal, many people suffer from occasional heartburn and regurgitation, where stomach contents flow backward up the esophagus. This reflux happens when the lower esophageal sphincter, the valve between the stomach and esophagus, inappropriately relaxes. No one is quite sure why it happens with some people and not others. Many incidences of reflux are physiologic (normal functioning), especially after a meal, and doesn’t require medical treatment (1).

Gastroesophageal reflux disease (GERD), on the other hand, is long-lasting and more serious, affecting as much as 28 percent of the U.S. population (2). This is one reason pharmaceutical firms give it so much attention, lining our drug store shelves with over-the-counter and prescription solutions.

GERD risk factors range from lifestyle — obesity, smoking and diet — to medications, like calcium channel blockers and antihistamines. Other medical conditions, like hiatal hernia and pregnancy, also contribute (3). Dietary triggers can also play a role. They can include spicy, salty, or fried foods, peppermint, and chocolate.

One study showed that both smoking and salt consumption added to the risk of GERD significantly (4). Risk increased 70 percent in people who smoked. Surprisingly, people who used table salt regularly saw the same increased risk as seen with smokers.

Let’s examine available treatments and ways to reduce your risk.

Evaluate medication options

The most common and effective medications for treating GERD are H2 receptor blockers (e.g., Zantac and Tagamet), which partially block acid production, and proton pump inhibitors (e.g., Nexium and Prevacid), which almost completely block acid production (5). Both classes of medicines have two levels: over-the-counter and prescription strength. Let’s focus on proton pump inhibitors (PPIs), for which just over 90 million prescriptions are written every year in the U.S. (6).

The most frequently prescribed PPIs include Prilosec (omeprazole) and Protonix (pantoprazole). Studies show they are effective with short-term use in treating Helicobacter pylori-induced peptic ulcers, GERD symptoms, and gastric ulcer prophylaxis associated with NSAID use (aspirin, ibuprofen, etc.) as well as upper gastrointestinal bleeds.

Most of the data in the package inserts is based on short-term studies lasting weeks, not years. The landmark study supporting long-term use approval was only one year. However, maintenance therapy usually continues over many years.

Side effects that have occurred after years of use include increased risk of bone fractures and calcium malabsorption; Clostridium difficile, a bacterial infection in the intestines; potential vitamin B12 deficiencies; and weight gain (7).

Understand PPI risks

The FDA warned that patients who use PPIs may be at increased risk of a bacterial infection called C. difficile. This is a serious infection that occurs in the intestines and requires treatment with antibiotics. Unfortunately, it only responds to a few antibiotics and that number is dwindling. In the FDA’s meta-analysis, 23 of 28 studies showed increased risk of infection. Patients need to contact their physicians if they develop diarrhea when taking PPIs and the diarrhea doesn’t improve (8).

Suppressing stomach acid over long periods can also result in malabsorption issues. In a study where PPIs were associated with B12 malabsorption, it usually took at least three years’ duration to cause this effect. While B12 was not absorbed properly from food, PPIs did not affect B12 levels from supplementation (9). If you are taking a PPI chronically, have your B12 and methylmalonic acid (a metabolite of B12) levels checked and discuss supplementation with your physician. Before stopping PPIs, consult your physician. Rebound hyperacidity (high acid produced) can result from stopping them abruptly.

Increase fiber and exercise

A number of modifications can improve GERD, such as raising the head of the bed about six inches, not eating prior to bedtime and obesity treatment, to name a few (10). In the study that quantified the risks of smoking and salt, fiber and exercise both had the opposite effect, reducing GERD risk (5). An analysis by Journal Watch suggests that the fiber effect may be due to its ability to reduce nitric oxide production, a relaxant for the lower esophageal sphincter (11).

Manage weight

In one study that examined obesity’s role in GERD exacerbation, researchers showed that obesity increases pressure on the lower esophageal sphincter significantly (12). Intragastric (within the stomach) pressures were higher in both overweight and obese patients on inspiration and on expiration, compared to those with normal body mass index.

Avoid late night eating

One of the most powerful modifications we can make to avoid GERD is among the simplest. A study showed a 700 percent increased risk of GERD for those who ate within three hours of bedtime, compared to those who ate four hours or more prior to bedtime (13). Therefore, it is best to not eat right before bed and to avoid “midnight snacks.” While drugs have their place in the arsenal of options to treat GERD, lifestyle changes are the first, safest, and most effective approach in many instances. 

References: 

(1) Gastroenterol Clin North Am. 1996;25(1):75. (2) Gut. 2014 Jun; 63(6):871-80. (3) emedicinehealth.com. (4) Gut 2004 Dec; 53:1730-1735. (5) Gastroenterology. 2008;135(4):1392. (6) Kane SP. Proton Pump Inhibitor, ClinCalc DrugStats Database, Version 2022.08. Updated August 24, 2022. Accessed October 11, 2022. (7) World J Gastroenterol. 2009;15(38):4794–4798. (8) www.FDA.gov. (9) Linus Pauling Institute; lpi.oregonstate.edu. (10) Arch Intern Med. 2006;166:965-971. (11) JWatch Gastro. Feb. 16, 2005. (12) Gastroenterology 2006 Mar; 130:639-649. (13) Am J Gastroenterol. 2005 Dec;100(12):2633-2636.

Dr. David Dunaief is a speaker, author and local lifestyle medicine physician focusing on the integration of medicine, nutrition, fitness and stress management. For further information, visit www.medicalcompassmd.com.

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Peter Westcott, on right, in the lab with technicians Zakeria Aminzada, on left and Colin McLaughlin, center. Photo by Steven Lewis

By Daniel Dunaief

When Peter Westcott was growing up in Lewiston/Auburn, Maine, his father Johnathan Harris put the book “Human Genome” on his bed. That is where Westcott, who has a self-described “obsessive attention to detail,” first developed his interest in biology.

Westcott recently brought that attention to detail to Cold Spring Harbor Laboratory, where he is an assistant professor and Cancer Center member. He, his wife Kathleen Tai and their young children Myles and Raeya moved from Somerville, Massachusetts, where Westcott had been a postdoctoral fellow at the Koch Institute of Integrative Cancer Research at the Massachusetts Institute of Technology.

Westcott will take the passion and scientific hunger he developed and honed to the famed lab, where he plans to continue studies on colon cancer and the immune system.

“A lot of things attracted me to Cold Spring Harbor Laboratory,” said Westcott who had been to the lab during conferences, joining three Mechanisms and Models of Cancer meetings, and appreciated that the small size of the lab encourages collaboration and the sharing of ideas across disparate fields.

At this point, Westcott, who purchased a home in Dix Hills and started on campus on September 1st, has two technicians, Zakeria Aminzada and Colin McLaughlin working with him. He will be taking on a graduate rotation student from Stony Brook University soon and would also like to add a postdoctoral researcher within about six months. He plans to post ads for that position soon. 

Research directions

Westcott said his research has two major research directions.

The first, which is more translatable, involves looking at how T cells, which he described as the “major soldiers” of the immune system, become dysfunctional in cancer. These T cells balance between attacking unwanted and unwelcome cells relentlessly, disabling and destroying them, and ignoring cells that the body considers part of its own healthy system. When the T cells are too active, people develop autoimmunity. When they aren’t active enough, people can get cancer.

“Most cancers, particularly the aggressive and metastatic ones, have disabled the immune response in one way or another, and it is our focus to understand how so we can intervene and reawaken or reinvigorate it,” he explained.

During cancer development, T cells may recognize that something on a tumor is not healthy or normal, but they sometimes don’t attack. Depending on the type of genetic program within the T cells that makes them tolerant and dysfunctional, Westcott thinks he can reverse that.

A big push in the field right now is to understand what the genetic programs are that underlie different flavors of dysfunction and what cell surface receptors researchers can use as markers to define T cells that would allow them to identify them in patients to guide treatment.

Westcott is taking approaches to ablate or remove genes called nrf4a 1, 2 and 3. He is attacking these genes individually and collectively to determine what role they play in reducing the effectiveness of the body’s immune response to cancer.

“If we knock [some of these genes] out in T cells, we get a better response and tumors grow more poorly,” he said.

Westcott is exploring whether he can remove these genes in an existing T cell response to cause a regression of tumor development. He may also couple this effort with other immunotherapies, such as vaccines and agonistic anti-CD40 antibody treatment.

As a second research direction, Westcott is also looking more broadly at how tumors evolve through critical transitions. Taking an evolutionary biology perspective, he hopes to understand how the tumors start out as more benign adenoma, then become malignant adenocarcinoma and then develop into metastatic cancer. He is focusing in particular on the patterns of mutations and potential neoantigens they give rise to across the genome, while concentrating on the immune response against these neoantigens.

Each tumor cell is competing with tumor cells with other mutations, as well as with normal cells. “When they acquire new mutations that convey a selective advantage” those cells dominate and drive the growth of a tumor that can spread to the rest of the body, Westcott said.

Using a mouse model, he can study tumors with various mutations and track their T cell response.

T cells tend to be more effective in combating tumors with a high degree of mutations. These more mutated tumors are also more responsive to immunotherapy. Westcott plans to study events that select for specific clones and that might shift the prevalence, or architecture, of a tumor.

Some of the work Westcott has done has shown that it is not enough to have numerous mutations. It is also important to know what fraction of the cancer cells contain these mutations. For neoantigens that occur in only a small fraction of the total cells in the tumor, the T cell responses aren’t as effective and checkpoint blockade therapy doesn’t work.

He wants to understand how the T cell responses against these neoantigens change when they go from being subclonal “to being present in most or all of the tumor cells,” he explained. That can occur when a single or few tumor cells acquire a selective advantage. His hypothesis is that these selective events in tumor progression is inherently immunogenic. \

By exploring the fundamental architecture of a tumor, Westcott hopes to learn the mechanisms the tumor uses to evade the immune system.

Ocean breeze

As Westcott settles in at CSHL, he is excited by the overlap between what he sees around the lab and the Maine environment in which he was raised.

“Looking out the window to the harbor feels like New England and Maine,” he said. “It’s really nostalgic for me. Being near the ocean breeze is where I feel my heart is.”

Before his father shared the “Human Genome” book with him, Westcott was interested in rocks and frogs. In high school, his AP biology teacher helped drive his interest in the subject by encouraging discussions and participation without requiring her students to repeat memorized facts. The discussions “brought to life” the subject, he said.

As for his work, Westcott chose to study colon cancer because of its prevalence in the population. He also believes colon cancer could be a model disease to study all cancers. By understanding what differentiates the 12 percent of cases that are responses to immunotherapy from the remainder that don’t respond as well to such approaches, he hopes to apply these lessons to all cancer.

“There is a huge, unmet need,” he said.

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Apple Blondie Cupcakes Photo from Family Features

By Heidi Sutton

One of my favorite things to do in the fall is to pack the camera and take a drive out east to visit the many farm stands before the colder weather sets in. This always includes a visit to May’s Farm in Wading River for pumpkins and mums and a stop at Windy Acres in Calverton for their large variety of apples, including the Mutsu apple. Also known as Crispin apples, they originated from the Mutsu Province of Japan in the 1940s and are a cross between the Golden Delicious and the Indo apple. Large in size with a yellowish-green skin, they are sweet and juicy with a crisp texture, perfect for following recipes. 

Apple Blondie Cupcakes

Apple Blondie Cupcakes
Photo from Family Features

YIELD:  Serves 12

INGREDIENTS: 

1 1/4  cups all-purpose flour

1/2  teaspoon baking powder

1/2  teaspoon kosher salt

1/2  teaspoon cinnamon

1/4  teaspoon nutmeg

1/2  cup unsalted butter (1 stick), melted    and cooled 

1 cup light brown sugar, packed

1 teaspoon vanilla extract

1 large egg, at room temperature

2 large apples peeled, cored and diced 

DIRECTIONS:

Preheat oven to 350 F. Line a 12-count muffin pan with cupcake liners and set aside. In medium bowl, whisk flour, baking powder, salt, cinnamon and nutmeg. In a large bowl, whisk butter and brown sugar 2 minutes, or until well combined. Add vanilla and egg; whisk until incorporated. Add flour mixture to large bowl of wet ingredients. Stir until just combined; be careful to not overmix. Fold in diced apples. Spoon batter evenly into cupcake liners. Bake 18 to 22 minutes, or until toothpick inserted into center of cupcake comes out clean. Let cool before serving.

Apple Crisp(in)

YIELD: Makes 4 to 6 servings

INGREDIENTS: 

4 cups apples, pared and sliced

1/4 cup orange juice

1/4 cup sugar

3/4 cup flour

1/2 teaspoon cinnamon

1/3 cup butter

DIRECTIONS:

Preheat over to 375 F. Mound apples in a buttered pie plate and pour orange juice over them. In a separate bowl, combine sugar, flour, and cinnamon. Cut in butter until mixture is crumbly. Sprinkle mixture over apples. Bake for 45 minutes or until apples are tender and topping is crisp. Top with vanilla ice cream and serve.

Easy Apple Turnovers

 

Easy Apple Turnovers
Photo from METRO

YIELD: Makes 4 servings

INGREDIENTS: 

1 1⁄2 cups thinly sliced, peeled apples

1⁄4 cup packed brown sugar

2 tablespoons water

1 teaspoon lemon juice

1 tablespoon all-purpose flour

1 tablespoon granulated sugar

1⁄4 teaspoon salt

1 tablespoon butter or margarine

1⁄2 teaspoon vanilla

1 box Pillsbury™ refrigerated pie crusts

1 egg

DIRECTIONS:

In a 2-quart saucepan, mix apples, brown sugar, 1 tablespoon of the water and lemon juice. Cook over medium heat, stirring occasionally, until bubbly. Reduce heat to low; cover and cook 6 to 8 minutes, stirring occasionally, until apples are tender. In a small bowl, mix flour, granulated sugar and salt. Gradually stir into apple mixture, cooking and stirring until mixture thickens. Remove from heat; stir in butter and vanilla. Cool 15 minutes.

Meanwhile, heat oven to 350 F. Let pie crust pouch stand at room temperature for 15 minutes. Unroll crust on ungreased cookie sheet. Spoon cooled fruit mixture evenly onto half of crust to within 1⁄2 inch of edge.

In a small bowl, beat egg and 1 tablespoon water; brush over edge of crust. Fold untopped half of crust over apple mixture; firmly press edge to seal. Flute edge; cut small slits in several places in top crust. Brush top with remaining egg mixture.

Bake 25 to 35 minutes or until crust is golden brown. Serve warm or cool. Drizzle with icing, if desired.

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