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peanuts with allergy sign


IgE antibodies have a propensity to attach themselves to mast cells and basophils, where they react with environmental antigens and stimulate the release of inflammatory mediators (e.g., histamine, leukotrienes). Reactions, which are marked by vasodilation, capillary permeability, and smooth muscle contraction, occur within seconds to minutes of exposure and are the cause of many difficult-to-treat conditions, including urticaria (hives), allergic asthma, allergic rhinitis, and anaphylaxis. Omalizumab (Xolair), a monoclonal antibody that binds IgE and blocks it from attaching to cells, was recently approved to prevent food allergies in adults and pediatric patients one year and older; it has been available since 2003 and carries indications for asthma, rhinosinusitis with nasal polyps, and urticaria. Its use in food allergies is based on a study that enrolled 180 patients (median age 7 years) with an allergy to peanuts and two or more of the following: cashew, milk, egg, walnut, wheat, or hazelnut. Patients received omalizumab every 2 to 4 weeks for 16 to 20 weeks, with dosing based on body weight and total IgE levels. The primary outcome was tolerance (i.e., no dose-limiting effects) of a ≥ 600 mg peanut protein oral challenge at the end of the treatment period. At the study's conclusion, 67% of omalizumab-treated patients met the primary endpoint compared to 7% in the placebo group. Results were similar for the six other food allergies in the inclusion criteria. Of note, patients with a history of food-induced severe anaphylaxis were excluded from the study.

Severe food allergies are frightening conditions, as affected individuals are often inadvertently exposed to their offending agent. Although the study was small and very high-risk patients were excluded, Xolair appears to offer some hope to patients and parents who live in daily fear of a life-threatening event.

AASLD proposes new name for fatty liver disease
fatty liver
If you find the terms "fatty" or "nonalcoholic" offensive, you will be relieved to know the American Association For the Study of Liver Diseases (AASLD) has taken up the cause to protect us all from these divisive labels. In a recent publication, they recommend abolishing the terms "nonalcoholic fatty liver disease" and "nonalcoholic steatohepatitis" because they are "stigmatizing" and replacing them with "metabolic dysfunction–associated steatotic liver disease," or MASLD for short. They claim, "The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification." A recent study in the JAMA already adopted the new name (see link below).

pills for heart failure


Sodium-glucose cotransporter (SGLT) 1 and 2 are transport proteins in the apical membrane of the nephron that reabsorb filtered glucose and sodium in the proximal tubule. SGLT1 is also present in the small intestine, where it facilitates the absorption of glucose and sodium from the lumen. SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) block renal SGLT2 and are approved to treat diabetes, kidney disease, and heart failure. Sotagliflozin (Inpefa®), a dual SGLT2/SGLT1 inhibitor that blocks renal SGLT2 and intestinal SGLT1, was recently approved to prevent CVD events in patients with heart failure or diabetes and CKD. Approval was based on the two trials summarized below.
  • In the SOLOIST-WHF trial, 1222 diabetics recently hospitalized for heart failure were randomized to sotagliflozin or placebo. Over a median of 9 months, a composite of CVD deaths and heart failure exacerbations was significantly lower in the sotagliflozin group (245 vs 355 events, p<0.001). [PubMed abstract]
  • The SCORED trial randomized 10,584 diabetics with chronic kidney disease (GFR 25 - 60 ml/min) to sotagliflozin or placebo. Over a median of 16 months, a composite of CVD deaths and heart failure exacerbations was significantly lower in the sotagliflozin group (400 vs 530 events, p<0.001). [PubMed abstract]

In both trials, sotagliflozin's effect was primarily driven by reduced heart failure exacerbations, as CVD death did not differ between groups. SGLT2 inhibition, which has a pronounced diuretic effect, is the likely mechanism behind the heart failure benefit. It's unclear if SGLT1 inhibition plays a role; a study comparing sotagliflozin to an SGTL2 inhibitor would be informative but is unlikely.

Sotagliflozin's side effects are similar to those of SGLT2 inhibitors (e.g., UTI, dehydration, yeast infections), except for diarrhea, which occurred in up to 9% of sotagliflozin-treated patients and may be secondary to intestinal SGLT1 inhibition. Maintenance dosing is 400 mg once daily, and the tablet should be taken within an hour of the first meal.
Studies shed light on testosterone replacement therapy (TRT) effects
older man lifting weights
The TRAVERSE Study, a randomized controlled trial comparing TRT to placebo in hypogonadal men, found that TRT did not increase the risk of cardiovascular events over 33 months, albeit average treatment length was only 22 months and testosterone levels in the TRT group were below typical targets (median of 371 ng/dl). The large size of the trial (N=5246) made it a desirable setting to evaluate other TRT outcomes, spurring a number of recently published substudies. Findings from those analyses are summarized below.
  • Erectile function and libido - TRT did not improve ED, while daily libido events (e.g., sexual activity, sexual thoughts, flirting, sexual daydreams, spontaneous erections), which had a baseline average of 1.8 per day in both groups, improved to 2.8 in the TRT group and 2.3 in the placebo group, yielding a difference of 0.47 that was statistically significant (p=0.011)
  • Bone health - small studies have found that TRT increases BMD, so it was surprising that TRT-treated subjects had a significantly higher fracture risk over a median of 3.19 years (3.5% vs 2.46%, HR 1.43, 95%CI [1.04 to 1.97])
  • Diabetes and insulin resistance - TRT did not reduce progression to diabetes among prediabetics, nor did it improve glucose control in diabetics
  • Cognition, sleep, mood, energy - TRT had a modest but significant effect on mood and energy but no effect on cognition or sleep
  • Prostate events - TRT did not increase the risk of prostate events (e.g., prostate cancer, acute urinary retention, prostate biopsy)

TRT proponents often tout it as a fountain of youth, and defining its true effects has been difficult, as past studies have been mostly small and heterogeneous. TRAVERSE helps close the knowledge gap and dispel some myths, but its short treatment duration and modest testosterone levels in the TRT group are significant weaknesses.

young woman with a migraine


Over the last eight years, three new classes of migraine medications have emerged. Two classes target calcitonin gene-related peptide (CGRP), a chemical mediator involved in eliciting migraine headaches, and the third is a serotonin agonist selective for receptor 5-HT1F, which differs from the nonselective triptans. Each class is summarized below.
  • CGRP antibodies (Emgality, Aimovig, Ajovy, and Vyepti) - monoclonal antibodies that bind CGRP and block it from stimulating its receptor. All drugs are given parenterally and approved for migraine prevention. In studies, the placebo-subtracted reduction in monthly migraine days was 1 - 2 with CGRP antibodies.
  • CGRP receptor antagonists (Qulipta, Nurtec, Ubrelvy, Zavzpret) - these drugs block the CGRP receptor. They are taken orally, except for Zavzpret, which is a nose spray. Qulipta is approved for migraine prevention, Ubrelvy and Zavzpret are approved for acute migraine, and Nurtec is approved for both. In studies, the placebo-subtracted reduction in monthly migraine days was 1 - 2 with Nurtec and Qulipta, while acute migraine response rates were 2 - 10% higher with Ubrelvy, Zavzpret, and Nurtec compared to placebo.
  • Lasmiditan (Reyvow) - Lasmiditan is a non-triptan serotonin agonist selective for the 5-HT1F receptor, which theoretically makes it safer in patients with cardiovascular disease. It comes in a tablet and is approved for acute migraine. In one study (N=3005), 38.8% of lasmiditan-treated patients (200 mg) were pain-free two hours after dosing compared to 21.3% of placebo-treated patients.

The upside of these medications is that they have few side effects, precautions, and drug interactions. The downside is their high cost and modest efficacy. Of note, placebo always does well in migraine trials, which may be because other headache syndromes that are more responsive to psychological persuasion are often misdiagnosed as migraines.
Effect of nirsevimab (Beyfortus) on RSV hospitalizations evaluated in open-label trial
infant lying in hospital bed with oxygen
Two prior studies found that nirsevimab, a monoclonal antibody against RSV virus, reduced symptomatic RSV infections by 6.9% in preterm infants (29 to <35 weeks gestation) and 3.8% in infants born ≥35 weeks. RSV hospitalizations, a secondary outcome, were reduced by 3.3% (p<0.001) and 1% (p=0.07), respectively. A third study using RSV hospitalization as the primary outcome was recently published. The HARMONIE trial randomized 8058 healthy infants born at ≥ 29 weeks gestational age (85% were born at ≥37 weeks) to nirsevimab or usual care before or during RSV season. At the end of the trial, RSV hospitalization occurred in 0.3% of nirsevimab-treated patients and 1.5% of the usual care group (p<0.001). Two infants in the nirsevimab group were admitted to the ICU compared to five in the usual care group. One patient in the usual care group was intubated, and no deaths occurred.

A major weakness of this study is its open-label design, as RSV hospitalization criteria were not standardized, and knowing the patient's nirsevimab status potentially swayed the admitting physician's decision. The authors were aware of this critique and tried to argue it away in a discussion that raised more questions than answers. Hard outcomes like ICU admission (7 patients) and mechanical ventilation (1 patient) were rare, as this was primarily a study in healthy term infants.

Collectively, these three studies show that nirsevimab reduces the severity of RSV infection, with infants born before 35 weeks receiving the greatest benefit. Its effect in healthy term infants is small and of questionable value. The CDC recommends all infants receive the shot, but these studies support prioritizing preterm infants, as 99% of term infants are fine without it. There was a shortage of nirsevimab during the height of last fall's RSV season, which means many preterm infants went without, thus showing the potential hazard of blanket recommendations that are common with the CDC.


Over-the-counter birth control now available

Opill box
Opill®, a progestin-only birth control pill containing norgestrel, is now available, making it the first oral contraceptive sold over-the-counter in the U.S. A one-month pack retails for $19.99, and a three-month pack costs $49.99. It can also be purchased directly from the manufacturer, Perrigo, on their website. The pill should be taken at the same time every day, and the box instructs patients to use a barrier method for 48 hours if they are more than 3 hours late in taking it. Another company is currently in talks with the FDA about marketing an over-the-counter combined oral contraceptive.

Combination inhaler with albuterol and budesonide available

asthma inhaler
Inhaled corticosteroids (ICS), short-acting beta agonists (SABA), and long-acting beta agonists (LABA) are the most commonly prescribed asthma treatments. Recent studies have found that as-needed ICS/LABA therapy is equal or superior to a daily ICS and as-needed SABA, contradicting traditional views that an ICS must be used daily to be effective. Recent GINA guidelines also recommend as-needed ICS/LABA therapy for most asthmatics. Keeping with the trend, Airsupra, the first inhaler to combine a SABA with an ICS, has been approved. It contains albuterol and budesonide and comes in a canister with 120 inhalations. Dosing is two puffs as needed with a max of 12 in 24 hours. It was superior to albuterol as a rescue inhaler in a double-blind study (N=3132) where participants were receiving maintenance ICS therapy.

"Wellbutrin DM" hits the market

bottle of tablets
A new antidepressant called Auvelity combines bupropion, a widely prescribed dopamine-norepinephrine reuptake inhibitor, with dextromethorphan, a cough suppressant that inhibits NMDA receptors. One caveat of the combination is that bupropion inhibits dextromethorphan's metabolism, increasing its exposure. Auvelity comes in one strength (dextromethorphan 45 mg/bupropion 105 mg), and maintenance dosing is one tablet twice daily. A very small 6-week study (N=87) found that it was superior to bupropion monotherapy for treating depression in adults. For those who are interested, GoodRx shows Auvelity costs more than $1000 for 60 tablets, while a one-month bupropion prescription and a bottle of dextromethorphan will set you back about $30.

Janus kinase inhibitor slows progression of type one diabetes

diabetic injecting insulin
A new strategy for treating type one diabetes is early immunosuppression to prevent beta-cell destruction. Building on that approach, a recent study evaluated the effects of baricitinib (Olumiant), a janus kinase inhibitor, on beta-cell function in newly diagnosed type one diabetics. Ninety-one patients were randomized to baricitinib (4mg/day) or placebo, and after 48 weeks, baricitinib-treated patients had significantly higher meal-stimulated C-peptide levels. Baricitinib is currently approved to treat rheumatoid arthritis, alopecia areata, and COVID-19.

Pneumococcal vaccine recommendations - there's an app for that

doctor using smartphone
For years, there were two pneumococcal vaccines, now there are four. Figuring out which vaccine to give, how many, and what to do with the previously vaccinated can be perplexing. To help with the confusion, the CDC has created an online and mobile app that tells which vaccine to administer based on the patient's age, medical conditions, and prior vaccination history.



  • Meniscal surgery - It's one of the most common orthopedic procedures performed, but does it do anything?
  • CPAP for sleep apnea - Sleep doctors are on every corner it seems, but what are the benefits of diagnosing and treating sleep apnea?
  • Knee injections - these treatments are popular among orthopedists and primary care doctors, but are they effective?
  • Pneumonia vaccines in adults - vaccine manufacturers, the CDC, and Medicare want everyone to get a pneumonia vaccine, so they must be highly effective, right?

Patients gain weight back after stopping GLP drugs
doctor measureing obese abdomen
Wegovy and Zepbound are all the rage as Americans struggle to contain their waistlines. At their highest doses, weight loss over a year averages 16% with Wegovy and 21% with Zepbound, which rivals the effects of sleeve gastrectomy. Two studies have now looked at what happens when people stop these medications. In the first one, 902 overweight adults (average BMI 38) were treated with Wegovy for 20 weeks and lost 10.6% of their body weight. They were then randomized to continue Wegovy or switch to placebo for an additional 48 weeks. At the end of the randomization phase, Wegovy-continuers lost an additional 7.9%, while the placebo group gained back 6.9%. In a similar study, 670 patients (average BMI 38) received Zepbound for 36 weeks, achieving an average weight loss of 20.9%. They were then randomized to continue Zepbound or switch to placebo for 52 weeks. At the end of the study, Zepbound-continuers lost an additional 5.5%, while the placebo group gained back 14%.

The results of these studies aren't surprising, given that once the medications wear off, appetite is no longer suppressed, and patients who struggled with overeating before return to their previous habits. Many patients don't want to take these medications for life, which brings them back to where all weight-loss journeys seem to begin and end - diet and exercise. As for those who complain about the drug prices, calorie counting and jogging around the block are free.
Studies evaluate antithrombotics for atrial fibrillation precursors
heart with atrial fibrillation tracing
Traditionally, atrial fibrillation (AF) has been diagnosed with ECGs, telemetry, or holter monitors that provide days of tracings. In the past 20 years, new implantable devices (e.g., loop recorders, implantable defibrillators, pacemakers) have been introduced that give continuous readings over months to years. Longer tracings are able to detect asymptomatic episodes of atrial tachyarrhythmias that have undetermined clinical significance. Two events that have been loosely defined are atrial high-rate episodes (AHRE) and subclinical AF. While criteria aren't standardized across professional organizations, the following definitions are often seen:
  • AHRE - atrial tachyarrhythmia episodes with a rate > 170 beats/min detected by cardiac implantable electronic devices
  • Subclinical AF - an asymptomatic AHRE lasting greater than 6 minutes and less than 24 hours

Observational studies have found these events, which often precede the development of clinical AF, are associated with a higher-than-normal but less-than-AF stroke risk, spurring two recent studies that evaluated the effects of antithrombotics in affected patients. The first study (N=2536) compared edoxaban to placebo in patients with AHREs. It was stopped early due to futility, as CV events were not significantly lower with edoxaban, and major bleeding was worse. The other study (N=4012) randomized patients with subclinical AF to apixaban or aspirin. After 3.5 years of follow-up, apixaban reduced stroke risk (0.78%/patient-year vs 1.21%/patient-year) but increased major bleeding (1.53%/patient-year vs 1.12%/patient-year).

These studies do not support anticoagulation in AHRE or subclinical AF, while recent AHA guidelines state that it is "reasonable" in certain high-risk patients. Over the course of both trials, a significant number of subjects developed clinical AF (18% and 24%, respectively), underpinning the importance of continued close monitoring.


A 45-year-old female comes to see you for her annual physical. She reports having gastric bypass surgery three years ago and says she followed up with her surgeon once and never went back. She asks you to order her routine lab work.

Given her history of gastric bypass, what lab work is recommended? Are any other studies indicated? Find out at the link below.