Digest 72: Feasting on Knowledge – A Special Holiday Digest

December 19, 2025 | By Nora Taranto

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Issue 72

12/19/2025

Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two

Appetizers

Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
-Jennifer DeSalvo MD, Joshua Gilman MD, Alyssa Mancini MD

• A new risk model for lung cancer screening? The HANSE study, a German prospective cohort study published in The Lancet, evaluated the effectiveness of using an established lung cancer risk-prediction model compared to standard screening criteria (the NELSON criteria) in Germany. The NELSON criteria identify patients ages 50-75 as high risk if they have > 15 cigarettes daily x 25 years, > 10 cigarettes daily x > 30 years, and quit smoking < 10 years ago or are currently smoking. The PLCOm2012 risk prediction model uses age, smoking history, ethnicity, education level, BMI, history of chronic obstructive pulmonary disease, personal history of cancer and family history of cancer to predict a patient’s 6-year lung cancer risk, with an estimated risk >1.58% considered appropriate for screening. 5,191 participants who met criteria by either or both approaches were enrolled and underwent a baseline low-dose CT scan and repeat imaging 1 year later. The primary outcome was the positive predictive value (PPV) for lung cancer detection with each screening modality. Patients who met “PLCOm2012 criteria only” included patients with lower education, a personal/family history of cancer, and a longer time since quitting, compared to those who met “NELSON criteria only”. During the screening period, 111 lung cancers were detected (85 early-stage), with 108 detected in the PLCOm2012-selected group compared to 85 in the NELSON-selected group. The PPV was 19.4% higher using PLCOm2012 than with standard screening, resulting in a lower number needed to screen (38.6 vs 46.1) favoring the risk-prediction model. Five year follow up is planned. (JG) 
• PCSK9 inhibitors move into the primary prevention space! The VESALIUS-CV trial, just published in NEJM, randomized 12,257 patients with known atherosclerosis or high-risk diabetes but without prior myocardial infarction (MI) or stroke to the PCSK9 inhibitor (PCSK9i) evolocumab vs placebo. Patients had to be on optimized lipid lowering therapy with a low density lipoprotein (LDL) >90mg/dL, a non-high-density lipoprotein of >120 mg/dL, or an apolipoprotein B > 80 mg/dL at randomization. Roughly a third of patients had high-risk diabetes without known atherosclerosis. The two primary endpoints were a composite of death from coronary heart disease, MI, or ischemic stroke (3-point MACE) and a composite of the 3-point MACE outcome or ischemic driven arterial revascularization (4-point MACE). At 4.6 years of median follow-up, there was a 25% risk reduction of 3-point MACE favoring the PCSK9i group (hazard ratio [HR] 0.75, confidence interval [CI] 0.65-0.86, p<0.001), with an absolute risk reduction of 1.8%. There was a 19% relative risk reduction of 4-point MACE favoring the PCSK9i group (HR 0.81, CI 0.73-0.89, p<0.001). Subgroup analysis showed benefit for those both with and without known atherosclerosis. (JG) 
• Is a single dose of the HPV vaccine sufficient? NEJM recently published the results of a noninferiority trial including 20,330 girls aged 12 to 16 who were randomly assigned to receive one or two doses of the bivalent or nonavalent human papillomavirus (HPV) vaccine. The primary endpoint was new HPV infection (type 16 or 18) occurring from 12 to 60 months after vaccination, and persisting for at least 6 months. The HPV infection rate difference between one and two doses of the bivalent vaccine was -0.13 infections per 100 participants (95% CI -0.45 to 0.15), and 0.21 infections per 100 participants (95% CI -0.09 to 0.51) for the nonavalent vaccine, both of which met the prespecified noninferiority margin of 1.25 infections per 100 participants. The trial also included 3005 unvaccinated participants who were enrolled in a nonrandomized survey to assess vaccine effectiveness. Vaccine effectiveness was at least 97% in each of the four trial groups. (AM) 
• GLP-1RA use before pregnancy: weighing the risks and benefits. JAMA recently published the results of a retrospective cohort study looking at gestational weight gain and pregnancy outcomes for singleton pregnancies exposed to glucagon-like peptide-1 receptor agonists (GLP-1RAs) around the time of conception (448 pregnancies), compared to non-GLP1-RA-exposed pregnancies (1344 pregnancies). Each GLP-1RA-exposed pregnancy was propensity-score matched to three unexposed pregnancies, and GLP-1RA exposure was defined as at least 1 GLP1-RA medication order between 3 years before and 90 days after conception. As GLP-1RAs are not recommended during pregnancy, these medications would have been discontinued in the exposed group shortly after pregnancy confirmation (random chart review confirmed this in 50 pts).  GLP-1RA-exposed individuals had a mean maternal age of 34 years and a mean pre-pregnancy BMI of 36; 84% had obesity and 23% had preexisting diabetes. GLP-1RA-exposed pregnancies had greater gestational weight gain than unexposed pregnancies (difference of 3.3 kg, 95% CI 2.3-4.2), a higher risk of excess gestational weight gain, greater mean birth weight percentile, and a higher risk of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy. (AM) 
• To continue oral anticoagulation (OAC) beyond 3 months for unprovoked venous thromboembolism (VTE) or not? That is the question. A target trial emulation study recently published in BMJ assessed adults receiving OAC (i.e. warfarin or direct OAC) for unprovoked VTE to compare those who continued anticoagulation beyond 90 days to those who discontinued after initial (90 day) treatment. 30,554 propensity-score matched pairs were identified in Optum Clinformatics Data Mart (Optum CDM), with a mean age 73.9 years, and 57% female. 67.2% had been diagnosed with a pulmonary embolism and 32.8% with deep vein thrombosis.  Those who continued OAC had lower rates of recurrent VTE (adjusted HR 0.19, 95% CI 0.13 to 0.29), higher rates of major bleeding (adjusted HR 1.75, 95% CI 1.52 to 2.02), lower mortality rates (adjusted HR 0.74, 95% CI 0.69 to 0.79), and greater net clinical benefit (adjusted HR 0.39, 95% CI 0.36 to 0.42), compared to those who discontinued after 90 days. This persisted among those using OACs for at least three years after VTE. (JD) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.
The transition from trainee to attending is often marked by a sudden and unnerving (and often self-imposed) expectation that you are now “supposed to know everything,” as Dr. Sophia Gorgens describes in her article, Lessons from Attendinghood. She eloquently captures this moment with precision and wit as it affects consequential and trivial decisions as a new attending, noting, “you prescribe antibiotic eye drops because you are afraid a conjunctivitis isn’t viral and could cause blindness… it’s the only way you’ll sleep at night.” She later goes on to recount her daily debrief with her cat, “because medicine stunts emotional growth.” Check out her poem published in JAMA for additional moments that will make you feel less alone when you wake up to check UpToDate at 2 AM.

– Jennifer DeSalvo MD   

The Main Course

Alexander Chaitoff MD MPH

Peer Reviewing the Holidays
Lots of major articles have finally been put into print in the last month. In a study that surely gave meaning to internal medicine interns everywhere repleting potassium, an open-label randomized trial reported that raising potassium levels to the high-normal range in patients with ICDs significantly cut their risk of arrhythmias, hospitalizations, and death compared to standard care. Meanwhile, in dueling studies assessing the benefits of beta-blockers after myocardial infarction in patients with normal ejection fractions, one trial found no benefits while another found a small effect driven by certain patients. And in nursing home residents with frailty, a trial reported that stopping antihypertensive agents did not affect mortality.

But with winter in the air, something even more important is on the horizon: the BMJ Christmas issue. For the uninitiated, the BMJ Christmas Issue was first published in 1982 and reports real research and opinions that typically have a humorous or satirical spin. The non-research articles are already trickling in, so we figured what better way to prime you for the imminent research article main course than to explore some highlights from Christmas Issues past.

Yes, that Buzzing is in your Head
I can confidently say we have all felt that buzzing and reached for our pagers only to find no new messages. I am confident because of a2010 BMJ Christmas issue article. Turns out, nearly seven out of ten medical staff have been haunted by “phantom vibrations”—that sensation your phone or pager is buzzing when, in reality, it’s sitting there as silent as Scrooge on Christmas morning. The study reported that residents were more likely to catch the phantom than attendings, especially if their device was stashed in a breast pocket and used on vibrate mode for long hours.

No parachute needed?
It is bioplausible that having a parachute increases survival after jumping out of a plane. In fact, the parachute paradox is a well-known critique of evidence-based medicine – some interventions are so obviously effective that randomized controlled trials are comically unnecessary. Turns out, heterogeneity of treatment effects can be considered even here. In a2018 BMJ Christmas issue article, researchers bravely randomized 23 volunteers to jump out of aircraft—with either a parachute or just an empty backpack. They found that parachutes don’t prevent death or injury when jumping from aircraft—as long as that aircraft is parked and grounded.

Go ahead, eat the cake
Nutritional epidemiology is a field that is fraught with confounding – a topic that has been written about extensively. I recommend ignoring that fact and just taking at face value this 2023 BMJ Christmas Issue article. Researchers dove deep into The Great British Bake Off’s Christmas desserts— conducting an “umbrella review of umbrella reviews of meta-analyses of observational studies”—and found that, statistically, those fruit, nutty, and coffee-laced treats might just nudge your health in a good direction. While they also reported that sugar and alcohol are the usual party poopers, they concluded on an upbeat note – recipes for Christmas desserts featured on the show use lots of ingredients associated with reductions in disease risk. So this holiday season, science says you can quite literally have your cake and eat it, too.

Read More from BMJ Christmas Here!

Digestifs

Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: Catch up this week on the latest updates in ASCVD risk evaluation and lipid management. In Episode #508, Dr. Laurence Sperling walks us through the new PREVENT calculator, when to use apoB testing, and so much more. 

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Until next time, keep that brain hole digesting! 

The Curbsiders Digest

Issue 72

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Jennifer DeSalvo,  Joshua Gilman,  Alyssa Mancini, and Nora Taranto report no disclosures.
Alexander Chaitoff reports consultancy for Alosa Health 
Kate Grant reports no disclosures.   

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