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Aw, Nuts! By: Sasha Klemawesch, MD

Aw, Nuts! By: Sasha Klemawesch, MD

Conventional wisdom for decades has been to avoid nuts and seeds if you have diverticulosis; however official Gastroenterology literature now says otherwise. Actually, it has for some time, but old habits die hard, and anecdotal rumors still heavily cloud the discussion both in the medical community and among lay people. While it’s not surprising that patients’ impressions may be skewed by rampant Reddit forums on the subject, doctors should be aware of the change in recs, seeing that literally hundreds of studies (more than 300 in the past decade) exist evaluating a variety of dietary effects on diverticular disease. Many of those specifically focused on seed and nuts, and none of them showed any increased harm or risk. The one diet that was affiliated with diverticulitis bouts? No surprise here: “Standard American Fare.” (fried foods, red/processed meats, heavily refined grains, sweets and high fat dairy products). I personally think a big reason why those are correlated with worse outcomes in diverticulosis is that they are all so constipating; and avoiding straining and incorporating fiber and hydration into your diet has long been known to be beneficial (both for diverticulosis as well as in people w/o it).

Now speaking of trying to turn the cruise liner that is diverticulitis management…. Antibiotics. The American Gastroenterology Association has had data out for years showing that we only started treating diverticulitis with antibiotics because “that’s what they always did.” When docs first started doling out Cipro/Flagyl to everyone, it wasn’t based on any scientific trials or evidence, it came more from a logical, hypothetical theory and resultant trial and error approach, and then got passed down from generation to generation. But we now have actual research data showing that uncomplicated diverticulitis in an otherwise healthy patient is more of an InFLAMMatory process, not an InFECTious one, and therefore treatment should include anti-inflammatories, not antimicrobials. Myself being a huge proponent of antibiotic stewardship, I love this change in practice, but it has been pulling teeth to get patients to accept it, and even to change the minds of my fellow colleagues; many of whom say “yeah, I heard about that literature, but I still cover them.” (meaning they prescribe them antibiotics) …  Cut to 4 days later when I see the patient back for their even worse diarrhea due to the antibiotic side effect. Now certain patients and certain cases (i.e. those w abscesses or perforations), still do need antibiotics, but your run-of-the-mill mild case, those do not.

I know many of you will have a hard time *stomaching* this news, so here is a high-quality source for you to check out and verify that I’m not blowing smoke up your behind (sorry couldn’t resist two GI tract puns) just copy this into your search bar:  10.1053/j.gastro.2020.09.059

Tincture of Time By: Sasha Klemawesh, MD

Tincture of Time By: Sasha Klemawesh, MD

In the preceding article I mentioned how antibiotics became accepted as standard treatment for diverticulitis; doctors considered which pathogenic bacteria would typically invade the gut, and drew a logical conclusion that if the colon was infected, then Cipro/Flagyl would treat it. The practice had staying power because patients seemed to get better while on said treatment. However, like many other entities commonly “treated” with antibiotics, it is not the antibiotic that is making the patient better, it is so-called Tincture of Time; the issue either has an inherently discrete duration and/or the patient’s body heals itself. It just seems like the antibiotics are helping because those two things coincide. This same phenomenon is the reason that so many people swear they MUST be prescribed a Zpack for their mild URI, or some Amoxil for their sinusitis. Both of those illnesses are far more commonly due to a viral trigger than bacterial, but because lazy doctors write for Zpacks at the drop of a hat, patients come to expect it. This is not good medical practice and is the reason for so much of the antibiotic resistance we have accrued in the US. While just like in diverticulitis, there is a role for antibiotics in certain cases of sinusitis or bronchitis, withholding them should be the rule for 90% plus of the cases, not the exception. So next time a doctor “refuses” to give you your precious Zpack, please know that it is more work for them to not simply acquiesce to your request, and thank them for actually having your best interest in mind.

O O O….Oh no! By: Sasha Klemawesch, MD

O O O….Oh no! By: Sasha Klemawesch, MD

If you are a non-streaming luddite like me who still watches cable, then I’m sure you could not only sing the Ozempic jingle on command, but probably do the Jardiance-Lady’s dance as well. There’s been so much hype around the novel diabetic agents, I thought it worth discussing some of their downsides, since otherwise mainly what you hear are social media-ites & bravo-lebrities lauding them as quick & easy weight loss hacks.

While it’s true (especially for the Ozempics/Mounjaro’s of the bunch), that they do help you lose weight, it’s also true that along w that desired benefit comes the potential for many adverse effects. 

Let’s look at Jardiance – aka – Empagliflozin first. This is an SGLT-2 Inhibitor, which is a different class from the others. It essentially makes your kidneys pee out boatloads of glucose, which in turn causes you to pee out high volumes of urine. The medical term for this is “osmotic diuresis.” If you remember from high school science, when you have two containers of water connected by a semi-permeable-membrane, one side w salt water, the other w tap, the tap water will selectively flow through to the side with the salt, in attempts to balance the ratio of salt: water on both sides. The kidneys do the same thing when you have excessive sugar in the urine; they send excessive water/fluid after it; which is why Jardiance not only lowers Blood Sugar, but also (partially) why it has a proven benefit in Heart Failure patients. (a key component of treating heart failure is keeping body fluid low, keeping patients ‘dry’). However, Glucosuria (glucose in urine) is also the reason for the main adverse effects I see time & time again in the ED; the 3 main ones being UTIs, Dehydration/Acute kidney failure, and Euglycemic Ketoacidosis.

UTI is simple enough. Bacteria love sugar, they need it to live and thrive. When you have too much sugar coursing through your genitourinary tract, bacteria show up to party, increasing the likelihood of infections throughout it.

Dehydration and Kidney Failure. Sounds scary, but Dehydration IS (in medical terms at least) the mild form of         “Pre-Renal Acute Kidney Failure.” It simply means that you’re so dehydrated that your creatinine level (aka “kidney number”) goes up a little when you run lab work. Treatment is very simple. IV fluids (or oral), and your labs go back to normal and everything is fine. Occasionally though, the degree of renal dysfunction can get severe enough to necessitate admission to the hospital for ongoing fluid resuscitation and lab monitoring.

Euglycemic Ketoacidosis. This is the most severe of the adverse sequalae that I have personally seen come through the ED. Most people have heard of DKA, Diabetic Ketoacidosis. This is similar in that it involves the pH level of your body becoming dangerously low, and requires treatment in the ICU w an insulin infusion. The difference here is that your glucose level is normal, and because of that, many times this condition can be overlooked and underrecognized, especially if you happen to be seen by a provider who is not aware of what it is or how it presents. Unfortunately, that is not uncommon, and it doesn’t help that its symptoms are quite vague; nausea, stomach upset, fatigue, weakness, etc. 

Now to the other family of meds which includes Ozempic, Victoza, Wegovy, Saxenda, Rybelsus, and Mounjaro. All but Mounjaro are GLP-1 Agonists. Mounjaro is both a GLP-1 and GIP Agonist. GLP-1 Agonism exerts several effects. It slows gastric emptying, so food stays in your stomach longer, you feel fuller longer and therefore naturally start eating smaller portions.  It also increases insulin production, decreases glucagon release (a hormone that raises blood sugar), and has direct effects in brain centers involved in both physiologic appetite and psychologic food cravings. It also affects acid secretion in the stomach (which can cause some nausea/ queasiness), and that, combined w the effects in the brain and the slowed gastric emptying all combine to severely curb appetite and food consumption. The GIP in Mounjaro does all the same things since GIP and GLP-1 are closely related hormones, but the addition of it leads to synergism such that all the effects are compounded and weight loss is augmented.

The most common complaint I see in these medicines is the nausea and stomach upset. The worst effect I have seen (and I have personally had 4 patients so far with it) is pancreatitis. Pancreatitis can range from painful but not dangerous to potentially life-threatening. Two of my 4 patients went to the ICU, one went to Med-Surg, and one went home.

Another increasingly common issue coming to light w these meds is that they are forcing surgeons and anesthesiologists to adjust their OR scheduling. While “nothing after midnight” has been the pre-op mantra for decades, nowadays 6 hours NPO is becoming woefully inadequate; patients are regurgitating and sometimes aspirating when they start to get put under, since food is staying in their stomachs for so much longer. They are having to either come off their meds briefly or try and not eat for prohibitively long times before the OR.

But probably the biggest drawback of these medicines is their cost and availability, since they are all quite expensive, and right now the demand is still eclipsing supply.

What is the bottom line of all this? All of these meds are wonderful additions to the diabetes and obesity medicine arsenals, but they are by no means miracle cures. If you are taking one or considering one, just be aware of and be prepared for possible side effects. You can help to avoid many of the common adverse effects of Jardiance by keeping up your fluid intake. Unfortunately, there is not much you can do to avoid being the unlucky one who gets pancreatitis.

But DO feel reassured that my POV is skewed, since I only see bad outcomes in the ED. There are millions of other people out there doing great on them….   And if you need proof, just turn on your TV!

Mushroom Misery

Mushroom Misery

Shiitake dermatitis is a big price to pay for the joy of shiitake mushrooms.  The dermatitis consists of intense itching that occurs shortly after ingesting raw or undercooked shiitake mushrooms.  Characteristic of the rash are raised, red streaks which is also called “flagellate erythema” because it literally looks like the sequela of being whipped.  Other than this characteristic appearance, the dietary history is the cue to diagnosis.    

It responds quickly to oral antihistamines and/or steroids.  It is prevented by adequate cooking of the mushrooms.  But some Eastern health supplements may also contain raw shiitake. 

The shiitake mushroom contains lentinan, a sugar molecule called 1,3 beta-glucan.  In mice experiments when its given intravenously it has anti-cancer and anti-viral benefits.  For cancer it disrupts harmful intra-cellular signaling that helps cancer spread.  For viruses it inhibits tissue cells from absorbing the harmful virus.  Given orally to mice it has no benefit.  It also increases the production of an immune molecule called interleukin-1 (IL-1).  It’s the IL-1 that causes vasodilation (dilation of skin capillaries) and rash. 

Supplements or Not 

Supplements or Not 

The Journal of the American Medical Association recently published a study done by scientists in Cambridge, Mass.  This group did refined chemical analysis on 60 different health supplements.  Their findings were very disconcerting.  Just 11 percent of the products contained an accurate amount of the key ingredients listed on the label.  Forty percent had none of the indicated ingredients.  Forty Five percent had inaccurate amounts varying from .02 percent of the amount listed to 334 percent of the amount listed. Finally, 8 percent of the products contained at least one compound prohibited by the US FDA. 

As opposed to prescription medicines, the FDA does not have authority to approve supplements before they are marketed.  The agency does require that OTC products contain what they indicate. 

Just because a product is on the market does not mean it’s safe, much less effective.  This is probably where an ounce of skepticism is worth a pound of cure.

Thymus

Thymus

Scientists at Mass General Hospital in Boston recently published findings on 1,150 adult patients in their hospital who underwent thymectomy (removal of the thymus gland). 

The thymus gland is a bit of a mysterious organ found in our chest that is most active in early childhood.  It is located in the chest between the lungs and just above the heart.  In infants the gland is large and completely covers the front of the heart. 

Until this recent study scientists have thought that the thymus played its key role in immune development in childhood and then withered away.  After puberty the gland shrinks to a very small size and is replaced by fat.  To surgeons it looks like a little blob of fat. 

In the Harvard study 2,300 adults had chest surgery and in 1,150 of them the thymus was removed during the surgery because “it was in the way” and was not felt to be needed.

For years, the thymus was felt to be only active during childhood.  It pumps out T lymphocytes, immune cells that have many functions.  The “new” T-cells can be formatted to do a variety of immunologic jobs.  Adults rely on memory T-cells, which are long lived cells that can be re-directed (teach an old dog new tricks) for special tasks.  Because of this “standard model of thymic function “the surgeons did not think removing it would be of consequence.  But it turns out that they were wrong. The thymus is not expendable after all. 

Within five years after surgery 8 percent of the thymectomy patients died compared to 3 percent of those whose thymus was not removed during the operation.  Cancer risk within 5 years was also double in the thymectomy group.  Finally, the thymectomy group had double the incidence of new auto-immune diseases. 

Needless to say, the Harvard scientists were shocked by these findings.  It is unclear what removal of the thymus changed.  Perhaps the “blob of fat” is still producing a few new T-cells.  Or perhaps the involuted thymus still subserves some type of immune-protective-surveillance not yet recognized.  At any rate these findings have led to both a change in surgical tactics and also new immunologic research to study thymic function in adults. 

Chronic PPI Use and Asthma

Chronic PPI Use and Asthma

New research shows that prolonged use of proton pump inhibitors (PPI’s) can increase the risk for developing asthma.  PPI’s are the “drugs of choice” for esophageal reflux, gastritis and gastric ulcers.  But their long-term use impacts the gut microbiome which in turn can cause immune dysregulation.  It is this “tilting” of immune function that increases the risk for asthma.  Prolonged use of PPI’s by women during pregnancy also increases the risk for their child to develop asthma. 

One strategy to lessen this risk is to use the PPI to gain control of the problem and then segue to an H2 antihistamine such as Pepcid (famotidine). 

Cross Reactive Epitopes & Food Allergy

Cross Reactive Epitopes & Food Allergy

A recent article in the Journal of Allergy and Clinical Immunology provided an update on our understanding of cross reactivity. 

First by way of definition an epitope is a discreet (usually small) portion of a molecule that is the binding target of an antibody.  In the case of allergic problems, the antibody is IgE.  By way of example think of distinguishing features that help you identify a car:  the Mercedes Star and the Dodge Ram. 

Allergy is directed at this epitope, not at the very large complete molecule.  As it turns out certain epitopes are found on both foods and airborne allergens.  The most common examples are crustaceans and dust mites, tree nuts and birch pollen, wheat and grass pollen.  The cross reactivity can be a two-way street where exposure to a food worsens an airborne allergy or vice versa.  Also, allergy shots for the airborne allergen can actually reduce the food allergy by desensitization reactivity to the shared epitope.  What will be very interesting to find out is whether desensitization to foods will help airborne allergy.  Food desensitization is still in its infancy with peanut desensitization being the main inroad in this regard.  But many academic centers have ongoing research to develop therapies for other common food allergens; milk, egg, wheat, soy and corn.  Stay tuned. 

Dear Dr. K;

Dear Dr. K;

I’ve seen you and multiple other doctors for what has been called unexplained chronic cough.  Now I’ve read about the new drug Gefapixant.  Do you think I’m a candidate?

My answer is a qualified yes. But before I continue my answer let me first give a summary of your own situation that might be of help to other kindred spirits.  Your cough is called “unexplained” because despite our best efforts the medical specialists you’ve seen have failed to find a cause.  Your primary doctor listened to your lungs (normal) and ordered a chest x-ray (normal) and a CT scan (normal).  Your ENT did nasal endoscopy and a sinus CT, both of which were normal.  Your allergist (me) did allergy tests that were negative.  Your pulmonary doctor did a series of breathing tests and even a methacholine challenge test, all of which were normal.  He did have you try some inhalers which did not stop your chronic cough.  Your gastroenterologist did an upper GI x-ray and then an endoscopy both of which were normal.  Your speech pathologist examined your larynx and vocal cords and found no abnormality.  And yet, you continue to cough. 

Gefapixant is an antagonist (blocker) of the P2RX3 receptor.  This receptor functions as a ligand-gated ion channel for nociceptor activation.  I’m sorry for all the big words, but basically a nociceptor is a sensor that tells a nerve that it is being stimulated.  This sensor is activated through an entrance doorway called an ion channel. 

As it turns out this particular receptor plays a role in sensing pain, sensing the need to empty our bladder and sensing the need to cough.  And you might correctly guess the medication is being studied for these applications as well. 

Compared to placebo Gefapixant 45mg twice a day reduced cough frequency and cough severity and improved cough-specific quality of life.  Its main side effect was causing taste perversion.

Dear Dr. K;  I read something that indicated chronic sinusitis can predispose to stroke.  It scared me.  Is it true? 

Dear Dr. K;  I read something that indicated chronic sinusitis can predispose to stroke.  It scared me.  Is it true? 

The short answer to your question is yes. But, the best answer to your question is maybe.  First of all, it is important to know that vascular problems in general whether due to blockage from plaque or due to a clot have inflammation as a common denominator.  Whether you’re talking about a coronary artery or a carotid artery or an intracranial artery its arterial inflammation that sets the stage for the problem.  By way of example, its arterial inflammation that acts as the “Velcro effect” enabling cholesterol plaque to build up.  As it turns out any repository of inflammation in the body can contribute to this “Velcro effect”.  Thus, chronic sinusitis has this potential.  But what is important to understand is that its untreated, smoldering chronic sinusitis that has this potential. 

There is some evidence that the proximity of the sinus inflammation to the carotid arteries and the intracranial arteries gives this a more potent negative effect in terms of stroke initiation. 

In your particular case you treat the chronic inflammation with your allergy shots, your Singular (a non-steroid respiratory anti-inflammatory) and your topical nasal steroid spray.  However, some people choose not to treat a chronic sinusitis and therein lies the potential mischief. 

The worst case I have personally seen was a patient of mine who had chronic infected sinuses producing yellow and green mucus who declined therapy from me, her PCP and an ENT.  She suffered both a stroke and a brain abscess from the condition.

Another way that chronic sinusitis might lead to stroke is due to self-medication with either topical or oral decongestants.  Both have the potential to raise blood pressure and pulse and

if used as a chronic therapy (as opposed to brief and occasional use) they can add to the hazard of stroke.