The Curbsiders Internal Medicine Podcast

Episode #472 – DIGEST: cfDNA & Cancer in Pregnancy, Vitamin K2 for Leg Cramps, PRN Antihypertensives, GLP-1 Agonists for AUD, Short-Course Antibiotics

Date: February 24, 2025
Panel: Dr. Matthew Watto (Host), Dr. Paul Williams (“America’s PCP,” co-host), Dr. Nora Taranto (Digest Editor), Dr. Laura Glick (Hospitalist & Guest)

Episode Overview

This “Digest” episode brings together the Curbsiders team plus guests Nora Taranto and Laura Glick to discuss recent impactful studies covered in the Curbsiders' Digest newsletter. The discussion spans five hot topics in internal medicine: incidental cancer detection in pregnancy from cell-free DNA testing; vitamin K2 for nocturnal leg cramps; the safety and utility of PRN antihypertensive medications in the hospital; the intriguing potential of GLP-1 agonists in alcohol use disorder; and the latest evidence supporting shorter antibiotic courses for bacteremia. The panel unpacks data, clinical implications, and their own reactions—with plenty of trademark humor.

Main Topics & Key Insights

1. Incidental Cancer Detection in Pregnancy via cfDNA Testing (IDENTIFY Study, NEJM, Dec 2024)

[03:16]

• Study Presented by: Dr. Nora Taranto
• Study Context: Non-invasive prenatal testing (NIPT) is increasingly used to screen for fetal chromosomal abnormalities, analyzing circulating cell-free DNA (cfDNA) in pregnant patients’ blood.
• Key Finding: Occasionally, these tests report “abnormal” or “non-reportable” results, which can signal maternal chromosomal abnormalities—sometimes incidentally identifying underlying malignancies in the mother.
• Study Design: Prospective follow-up of 107 women with abnormal/non-reportable NIPT results, evaluating for occult malignancy via whole-body MRI, labs, physical examination, and fecal occult blood testing.
  • ~50% (52/107) were found to have cancer, commonly lymphomas (especially Hodgkin’s), colorectal, and breast cancer.
  • Some cancers were early stage and treatable with curative intent.
• Practice Implications:
  • There's no guideline on managing “non-reportable” NIPT results.
  • Quote [09:52]: “...we are not really set up to get these whole body MRIs and do all this testing—but since this test is already being used and now this information's out there, you’re going to have to do something with these patients…” – Dr. Watto
  • Current infrastructure and insurance may not support workup like whole-body MRI, presenting a challenge if this becomes common.
• Panel Take: Not quite practice-changing, but a crucial trend to follow and one that may require new systems for triaging and workup.
  • Quote [12:34]: “I feel like most things I think about are in the ‘to be tracked closely’ category. And this is definitely one of those.” – Dr. Taranto

2. Vitamin K2 for Nocturnal Leg Cramps

[17:24]

• Study Presented by: Dr. Watto
• Study Context: Nocturnal leg cramps are common in older adults, distressing but often benign. Prior studies examined pickle juice; now, focus turns to vitamin K2 (menaquinone-7, MK-7).
• Study Design: RCT (Tan et al., JAMA Intern Med, Dec 2024), adults ≥65 years with ≥2 nocturnal cramps in 2 weeks randomized to 180mcg K2 vs placebo nightly for 8 weeks.
  • K2 arm: ~2.7 fewer cramps/week compared to placebo, plus slight reductions in severity and duration.
  • No significant adverse events. Warfarin users excluded.
• Key Discussion Points:
  • Mechanism unclear; possibly involves calcium/muscle contraction.
  • Participants with diuretic use or neuropathy were excluded, so generalizability limited.
  • K2 is inexpensive and widely available.
  • Quote [23:34]: “As long as the person’s not taking a vitamin K antagonist like warfarin, then I don’t see the harm in trying this...buy a bottle, try it out, see if it helps.” – Dr. Watto
• Panel Take: Enthusiastic about low-risk, low-cost options for a common problem. Potential to recommend, especially given safe profile (except with anticoagulants).
  • Fun fact [24:45]: Vitamin K2 is rich in fermented foods, soft cheeses, eggs, meats, and possibly even pickle juice.

3. PRN Antihypertensives in the Hospital — Risks Highlighted

[25:42]

• Study Presented by: Dr. Paul Williams
• Study Context: Routine use of PRN antihypertensives in-hospital for asymptomatic high BP is common but controversial; prior studies suggest possible harm.
• Study Design: Retrospective cohort, emulated RCT (JAMA Intern Med 2024), VA system, >130,000 admissions, comparing those who received PRN antihypertensives vs those who did not.
  • Outcomes: time to first acute kidney injury (AKI), composite of MI, stroke, or death.
  • Findings: 20% received PRN antihypertensives; those receiving IV PRNs had 64% higher risk of AKI; increased odds of rapid drops in BP and adverse composite outcomes.
  • Quote [27:05]: “Not surprisingly, the patients that received IV only PRN antihypertensives had a 64% increased risk of actually having the acute kidney injury, but all groups had an increased risk of acute kidney injury.”
• Key Discussion Points:
  • Cause for hypertension often not explored (pain, meds, anxiety, sleep disruption, etc).
  • The threshold for PRN order (often SBP ≥180) and order sets reinforce unnecessary use.
  • Limitation: mostly male VA cohort; AKI outcome uses sensitive but not always clinically significant definition.
  • Quote [31:33]: “It’s very easy to reflexively respond by ordering an antihypertensive medication to feel that you are doing something...but it is so, so important to realize that the use of these as-needed blood pressure meds may actively harm the patients.” – Dr. Laura Glick
• Panel Take: Yet another nail in the coffin for this routine practice, but culture/EMR inertia persists outside academic settings.
  • Quote [32:26]: “...it should hopefully be one nail in the coffin that will eventually close this practice.” – Dr. Watto

4. GLP-1 Agonists for Alcohol Use Disorder (AUD)

[34:30]

• Study Presented by: Dr. Laura Glick
• Study Context: Animal and some human data suggest GLP-1 agonists (semaglutide, liraglutide) may reduce alcohol cravings and consumption.
• Study Design: Swedish registry cohort, >220,000 patients (ages 16–64) with AUD, median follow-up 8.8 years, compared periods on/off GLP-1 agonists.
  • Semaglutide/liraglutide associated with a significant decrease in AUD-related hospitalizations; not seen with other GLP-1s.
  • Standard AUD meds (naltrexone, disulfiram, acamprosate) had only modest benefit.
  • Limitations: Observational design, potential confounding (those who can access GLP-1s may be systematically different); can’t prove causality.
• Key Discussion Points:
  • Panel emphasized need for RCTs to confirm effect.
  • Ongoing/future RCTs of GLP-1s in AUD, opioid use disorder, and smoking noted.
  • Quote [38:14]: “There’s a lot of intangibles that are just hard to measure with these retrospective trials...the capacity for self-care...I don't know that they fully capture the medication effect in and of itself as opposed to the systems that allow that medication to be administered...” – Dr. Williams
  • Adverse effects and optimum duration for addiction indications unknown.
• Panel Take: Exciting avenue—worth considering for AUD patients who already meet approved GLP-1 indications (obesity, diabetes), but not yet practice-changing for alcohol use disorder alone.
  • Quote [42:24]: “It’s really not ready for primetime. It’s not practice-changing yet...But I do think it’s worthwhile considering these results when you’re treating patients with AUD plus obesity or type 2 diabetes...” – Dr. Laura Glick

5. Short Course Antibiotics in Bloodstream Infections (Balance Trial)

[43:50]

• Study Presented by: Dr. Nora Taranto
• Study Context: Optimal antibiotic duration for “uncomplicated” bacteremia is debated.
• Study Design: NEJM, Nov 2024, the “BALANCE” trial: BActeremia Length Actually Needed for Clinical Effectiveness.
  • 7 days vs 14 days of antibiotics for adult patients with bloodstream infections, excluding S. aureus, untreated abscesses, immunocompromised, etc.
  • Primary outcome: 90-day all-cause mortality—14.5% in 7-day arm vs 16.5% in 14-day arm; met non-inferiority margin.
  • Broad spectrum of causative organisms: gram-positives and gram-negatives, sources included UTI, pneumonia, intra-abdominal infection.
• Quote [44:11]: “Bravo. God bless the ID doctors.” – Dr. Williams (on the trial acronym)
• Panel Take: Seven days is non-inferior to fourteen for most bacteremias (excluding key exceptions: S. aureus, prosthetic/septic joint, deep abscess, or immunocompromised). Encourages shorter courses to limit adverse effects, resistance, and cost.
  • Quote [46:45]: “I’ve definitely seen...a trend toward decreased duration of antibiotics. I’m not sure if we’re fully there, but I do think this study is very promising...” – Dr. Laura Glick

6. Quick Take: Self-Collected HPV Screening

[48:29]

• Overview: USPSTF now supports self-collected (including in-clinic and likely soon home) HPV swabs for cervical screening, primarily for women age ≥30.
• Implications:
  • Home or self-swab collection has similar concordance to clinician-collected samples.
  • Could reduce barriers and improve screening uptake for patients avoiding in-office pelvic exams.
  • FDA approval for true “at home” mailing still pending; presently, only clinic self-collection is allowed.
  • Quote [51:14]: “Even if the patient has to be in the clinic to do the self-collected, it’s still more patient-centered than having the clinician do it.” – Dr. Watto

Notable Quotes & Memorable Moments

• Acronym Banter:

  • [04:44] Dr. Williams: "Now just listen, you cowards. Straight-up acronyms or just don’t even bother."
  • [44:11] Dr. Williams: “Bravo. God bless the ID doctors.” (on BALANCE acronym)

• On PRN Antihypertensives:

  • [31:33] Dr. Glick: "It is so, so important to realize that the use of these as-needed blood pressure medications may actively harm the patients."

• On Practicality of cfDNA Cancer Workup:

  • [09:52] Dr. Watto: "But since this test is already being used and now this information’s out there, you’re going to have to do something with these patients when you come up with these results."

• On Vitamin K2 for Cramps:

  • [23:34] Dr. Watto: "...I don’t see the harm in trying this. It looks like it’s relatively cheap...buy a bottle, try it out, see if it helps."

• On GLP-1s and SDOH:

  • [38:14] Dr. Williams: "There’s a lot of intangibles that are just hard to measure with these retrospective trials...the capacity for self-care...I don't know that they fully capture the medication effect in and of itself as opposed to the systems that allow that medication to be administered..."

• On Short-Course Antibiotics:

  • [44:11] Dr. Williams: “Bravo. God bless the ID doctors.”
  • [46:45] Dr. Glick: “Very promising...a lot of hope...this is just kind of adding on some other good studies and data that maybe shortened antibiotics is where we’re going.”

Timestamps for Major Segments

• [03:16] Incidental cancer detection with cfDNA in pregnancy (IDENTIFY study)
• [17:24] Vitamin K2 for nocturnal leg cramps
• [25:42] PRN antihypertensives in the hospital—risks and practice implications
• [34:30] GLP-1 agonists and alcohol use disorder (AUD)
• [43:50] Short-course antibiotics for bacteremia (BALANCE study)
• [48:29] Self-collected HPV screening: new guidelines and implications

Language and Tone Notes

• Conversational, with gentle humor and frankness
• Panel frequently teases about study acronyms and clinical trivia
• Clear attempts to connect guidelines with everyday clinical scenarios
• Candid acknowledgment of study limitations, insurance/system barriers

Takeaways for Clinical Practice

• cfDNA in Pregnancy: Incidental findings from NIPT that signal maternal risk of cancer may become a bigger issue—clinicians will need new workflows for risk assessment and triage.
• Leg Cramps: Vitamin K2 appears safe, low-cost, and modestly effective for refractory nocturnal cramps—an option for interested patients not on anticoagulant therapy.
• PRN Antihypertensives: Strong signal that reflexive PRN antihypertensives for asymptomatic inpatients should be avoided; focus instead on assessing cause of hypertension.
• GLP-1s for AUD: Intriguing but not ready for routine use; consider in patients with diabetes/obesity and AUD. Awaiting high-quality RCTs.
• Short-Course Antibiotics: 7 days non-inferior to 14 for uncomplicated bacteremia (non-S. aureus)—supports ongoing “shorter is better” movement.
• HPV Self-Screen: Self-collected swabs are now on par with clinician collection for screening—should expand accessibility once FDA approves at-home tests.

[End of Digest Episode Summary]