Update on Atrial Fibrillation (Goyal, 1/26/2026)

A recording of this presentation is available HERE.

***
Many thanks to Dr. Rajat Goyal for a fantastic Update on Management of Atrial Fibrillation, which has really changed over the last few years. Many of us trained in a time where we were taught that "rate control is as good as rhythm". We got pretty accustomed to starting a rate med (beta blocker or calcium channel blocker) and a DOAC and leaving it at that. . . that mantra of the 2000s is not quite right anymore. Turns out that rhythm control is the way to go!

Practice changing pearls:

• Afib begets Afib
• Everyone with atrial fibrillation (including paroxysmal) should be referred to EP 
• Ablation shows better outcomes (decreased progression, improved morbidity and mortality) than medication management alone
• The earlier the ablation, the better (i.e. within first year of onset) because AF is a progressive disease
• Patients with heart failure and AF definitely benefit from ablation
• Patients s/p ablation who show no AF at one year can safely discontinue anti-coagulation
• Lifestyle modification is important: weight loss, alcohol/tobacco use, hypertension and DM management, OSA, and stress

Rhythm vs Rate Control: 

Older studies showed no difference in M&M, BUT subsequent analysis found that patients in sinus rhythm and on anticoagulation had lower risk of death (AFFIRM trial). 

EAST-AFNET trial showed that early rhythm control associated with lower M&M (death, stroke, HF admits, coronary events). Of note, many were treated with anti-arrhythmic, not all were converted via ablation

Once in persistent AF, rhythm control efforts no longer effective. Essentially, AF begets AF due to the structural changes that lead to permanent changes in the conduction system

Ablation:

• Goal is to kill triggers that initiate afib and kill unhealthy tissue. They approach the pulmonary veins and electrically isolate them, but also look at LA, LA appendage, RA, etc.
• Ablation is MORE effective than ablation in controlling AF and maintaining sinus rhythm, and the earlier the better.
• Fewer progress to eventual persistent AF after ablation

What about in setting of HFrEF?

• Yes, they benefit from ablation!
• AF causes decreased CO, RVR, loss of atrial systole and increased MR and TR so in patients with HF, maintaining sinus rhythm is VERY important.
• The CAMERA-MRI study 2017 showed that after ablation the EF improved 18% after ablation compared to 4% with medical rate control.
• A follow up study also showed reduction in mortality, hospitalization after ablation thus became a Class 1 indication (including paroxysmal AF)

 

Ablation Modalities: Pulsed Field Ablation (PFA) created at UCSF in early 80s and alters cell membranes. The mapping is done via catheter which maps the LA and PVs and able to find high areas of voltage to ablate. Pulsed Field ablation a bit more effective than Thermal ablation

Technique isolates PV about 80%.

Complications of ablation: atrial-esophageal fistula. PFA allows more selective injury and less injury to esophagus (so far 0 events). Tamponade < 1%, stroke <.05%, AE fistula <1%, vascular events <3%, coronary spasm 0.14%

Who needs to be on Anticoagulation?

Left Atrial Appendage is where many clots form, so closing that area with Watchman after ablation helps reduce stroke significantly

Ablation + closure vs Ablation + anticoagulation: no difference in strokes long term

See image below:

• for patients with a low CHADS2VASC score (<2 for men and <3 for women), if you can prove no AF at 1 year post ablation, they can safely STOP anticoagulation
• for patients with a higher DHADS2VASC score, most should either be continued on anticoagulation OR be referred for a LAA occlusion.

Smartwatches?

What about everyone with their smart watches? Turns out that smartwatches have terribly sensitivity but pretty good specificity. SO, if a patient has NO AF on their watch, they probably don't have AF. On the other hand, just because the watch shows AF doesn't mean they actually have AF. Intermittently monitor every few months, but consider encouraging your patients to get a smartwatch

Lifestyle modification 

Lifestyle modification is still a mainstay of treatment/prevention of Afib. Patients with AF really need to be counselled on weight reduction, blood pressure management, glycemic control (if DM), alcohol and tobacco use, stress management. They should also be assessed and treated for OSA. Working on these risks is essential for long term maintenance of sinus rhythm 

The Care of Children with Medical Complexity (Naber, 1/21/26)

A recording of this presentation is available HERE.

Deep gratitude this week to Dr. Urs Naber, CPMC PICU Medical Director, who jumped in last minute to give a moving Grand Rounds this week on the Care of Children with Medical Complexity (CMC). Please do watch his presentation at the above link if you are interested in the topic. 

In the literature 0.7-11% of ALL children have medical complexity (definition somewhat vague)>> about 1-2% of all children

Defining CMC: chronic condition + substantial family needs + functional limitation + heath care utilization

• previously CF patients were the highest percentage of CMC, but new treatments has changed this.
• Any medical condition can count as a chronic condition, depending on its length >> technology dependence is a driver that makes this population so vulnerable

Children with CMC have specific in home needs: medical equipment, medication administration, assistance with ADLs. CP/MD often have respiratory support technology and functional limitations that lead to high needs and high healthcare utilization

Dr. Naber shared with us a video (included in the link of the full presentation above) about a child with medical complexity named Connor and his two dads and four adopted siblings. Connor was born with Trisomy 9 and is G-tube dependent, wheelchair bound, non-verbal. The video really showed us how complex it is to take care of these children, a reminder of what it means to families to be together. Reminder to

CMC have a substantial impact on healthcare, which is expanding, 2006 <1% population, making up 10% of pediatric hospitalizations, 25% of all hospital days, 41% of all healthcare costs (attributed to hospitalizations). . . 2022, now 1-2% of population, 63% of hospitalizations attributed, 79% of all hospital days, 84% of healthcare costs. Many times these kids have to stay in ICU for their respiratory care. 

Why is this happening? 

• increased survival for children with chronic conditions (e.g. spina bifida, esophageal atresia, biliary atresia, congenital heart disease, prematurity>> previously led to non-survival, but over the last 50 years, rate of survival has increased and continues to increase)
• Total ICU costs are driven dramatically by CMCs (see image below), only 10% of pediatric critical care do not have chronic disease
• ED visits: CMCs comprise 20-30% of all visits (even though 1-2% of population), most commonly respiratory infections, medical device malfunction
• presents unique challenges for ED physician (medical complexity, long medlists), as well as caregiver and patients (subspecialists not available, ED is dangerous)

Dr. Naber shared data from Houston looking at the impact of a comprehensive care program  (JAMA, Mosquera, et al 2014), over 3 year timespan>> care coordinator, nurse, cluster care, how much would that effect care?

• 52% reduction in ED visit
• 55% reduction in days of serious illness
• 42% reduction in cost (including the comprehensive care costs)
• time investment decreased over time>> had to invest 6 hours/month per child up front, down to 2 hours/month per child over time  and still maintain the drastic impact (see image)

Helping families cope with medical complexity-- surrounding structures really matter 

Dr. Naber reminded us of the IHSS program in California, which allows parents to get some income for their caregiving of children with medical complexity. Doesn't cover medical care, but does help cover ADLS (feeding, bathing, clothing)>> family  must register and become a provider through the program. Payment is low but is something for parents who are unable to work due to their children with medical complexity. Caregivers with CMC experience an overwhelming burden (almost double) of financial hardship (JAMA 2025)

Families of CMC struggle with cost of living, housing instability, transportation challenges. 

Access to specialists and subspecialists is particularly challenging: long wait times (more pronounced if poor or brown in CA). These access challenges add to the parental burden>> leading to missed work/school days, delays diagnosis, delays treatment, etc.

Subspecialty access is only readily available in concentrated metropolitan areas of California (SF Bay area and LA area). See map. Most children don't have adequate access. 1/3 of CMC families report they have drastic challenges accessing pediatric specialty care. Can be average 84 minutes of travel one way to access specialists>> every trip is one day. Again, time off work, paying cost, finding childcare for other children. Though families still prefer in person care (over telemedicine)-- feel more of a connection, get physical exam, etc

Transitions of care can be complex: this includes discharge from hospital (changes in meds/regimens), but also the huge transition when patients age out and become adults. Family physicians can care for these patients as children and continue caring for them as they become adults. In SF Bay Area 1,000 CMC age into adulthood (50% of CMCs)>> these patients continue to have high healthcare utilization rates. 

What are additional supports:

• Evidence from the same Houston comprehensive care program>> adding telemedicine support showed even better outcomes and even more decreased cost
• CMC Emergency form, better for patients, caregivers and doctors (especially ED)
• some states have CNA model, where caregivers can get additional training and payment for medical care
• patient/care navigators 
• CPMC in process of building a Bridge program, hoping that will move care for CMC in our area to the next level, where they can get subspecialty access and better long-term care

Migraine: physiology, new medications, and integrated approaches to management (Dacre, 1/14/2026)

A recording of this presentation is available HERE.

Many thanks to Dr. Mike Dacre for a presentation this week on Migraines. 

My notes:

Migraine syndrome is super common (~10% of all people), 1 billion people globally, 2nd cause of disability worldwide, 50% underdiagnosed and undertreated. 2:1 female to male ratio

• Migraine headaches 4-72 hours
• Note Pediatric usually max 2-4 hours (often not unilateral)
• Classic pattern of prodrome>> aura>> headache>> postdrome

What causes migraine? Has long been thought of as a blood vessel problem (spasm vs dilation)>> pain often pulsatile, worse with movement/position changes, vasoconstrictors (caffeine, ergo alkaloids) then migraines get better, vasodilators (Viagra) make migraines worse. 

BUT this understanding is now known to not be true. In actuality, the blood vessel changes are SECONDARY. Now belief is that migraine is primarily a disease of neuronal activity: large ion shifts (potassium, glutamate, ATP across cell membranes)>> two receptors particularly notable now, include CGRP receptor and PACAP

• CGRP is potent vasodilator, but is a side effect of activation of this cascade>> mast cell degranulation, inflammation and sensitization
• get irritation and inflammation around the blood vessels, causing painful vasodilation

Migraines tend to start in the brainstem (where trigeminal nerve originates), direction impacts the type of migraine a person experiences. Where it moves, impacts the symptoms/manifestations

I love this simple diagram of how genetic set point+ cumulative burden push people toward migraine thresholds and lead to migraine syndromes:

Migraine headaches can move from being episodic to being chronic/intractable. Once you get migraines frequently enough, you can get medication overuse headaches, which then push you to central sensitization, which makes you more likely to get migraines. Similar to chronic pain syndrome progression>> it is not uncommon for people with headache syndromes to not seek care, overtake meds, and then have their disease progress to central sensitization and "chronification".

Abortive Treatments

Medications 

• NSAIDs are very effective (shouldn't be taken more than QOD due to risk of medication overuse headache)
• acetaminophen and caffeine can potentiate/help (care with overuse)
• Excedrin is "worse" for medication overuse (no more than 5 times/month)
• Corticosteroids + PPI
• short course of prednisone has good evidence (NNT 9)
• Triptans (actually inhibit CGRP release)
• should be used in episodic migraine, more effective when done before pain starts (aura phase), not useful after 1 hour after onset of pain
• NNT 4-5
• Sumatriptan and Rizatriptan are most commonly used (familiarity)> no head to head trials
• Care with vasoconstriction effect (e.g. contraindicated in CAD, uncontrolled Htn)

• Opioids don't work well, high risk for misuse/dependence
• Caffeine is very effective in some people for aborting migraine, but people with > 2 cups coffee/day have more frequent and worse migraines
• Ditans: not available in US (schedule 5) but do see them in Middle East and Latin America

Nerve Blocks

Greater occipital nerve block>> safe and effective even in people who don't have predominant occipital pain, helps to abort migraine. 

• can be done with or without ultrasound
• Can do block + anti-emetic + steroid
• lidocaine+ bupivacaine
• very safe (low vascular, infection risk)

Preventive Treatments

Medications

• Beta blockers all work (propranolol, metoprolol)
• TCA: Amitriptyline
• SNRIs
• ARBs
• Anti-seizure meds (e.g. valproate, topiramate)>> best responders are people who failed other classes
• Anti-CGRPs: American Headache Society released guidelines in 2024 that these meds are first line for anyone with migraine >15 days/month ($600-700/month)
• safe and effective
• can be prescribed by PCPs
• can get covered by PHP (prior auth)
• one comparison study vs. topiramate, better tolerated
  
  
• Gepants
• remigapant, ubrogopant (can be used for ppx and abortive)
• Supplements
• Magnesium 400mg/day (moderate evidence)
• Riboflavin 400mg/day (good evidence)
• Coq10 (not great evidence) 100 TID
• Botox NNT 9 (50% reduction in HA days)
• Acupuncture NNT 11 (weekly acupuncture, 50% reduction in HA days)
• OMT/PT/massage are all also very effective, studies to support their use in reducing HA days

Summary:

Non-Beneficial Treatment (Garson Leder 1/7/2026)

 A recording of this presentation can be found HERE (will be added as soon as it is available).

***

Thanks to our Sutter bioethicist, Dr. Garson Leder, for a thoughtful presentation on Non-Beneficial Treatment. This is a heavy (and heady) topic, and I recommend you listen to the presentation if you want to get into the weeds on bioethical conundrums. 

If you just want the brief notes, keep reading!

Any good ethics lecture begins with terms and definitions:

• Medical Futility: a treatment is highly unlikely to benefit a patient or achieve a meaningful goal 
• quantitative futility: the chance of expected benefit is judged to be so low as to not justify treatment (sometimes but not always defined loosely as <1% chance of success, though numbers as high as a surgery that only has 30% chance of success may also fall into this category)
• qualitative futility: the quality of the expected benefit is judged to not justify treatment (quality as defined by who?)
  
• physiological futility: the treatment cannot achieve its intended purpose
• Moral authority: the right to make a decision for another person. 
• What gives physicians the power to be the decision-maker/moral authority?
• medical knowledge and experience (medical professionals are often right about likely outcome/course)
• don't patients still have right to make other/different decisions for themselves (i.e. do we have moral standing to unilaterally refuse treatment?)

(Resource allocation-- the question of should one be using limited resources to accomplish a specific goal-- is a different question)

A few pearls
-Continuing treatment is, no matter what, a decision

-Consider using the term "potentially inappropriate" rather than medically futile or even non-beneficial

-CA law supports the right of physicians to decline to continue care if it is deemed medically ineffective and/or is considered with "standard of care"

-Most conflicts about non-beneficial treatment can be resolved with clear communication AND time. 

MAT in the Fentanyl Era: Updates on Rapid Initiation and Titration (Dembar & Rubin, 12/17/25)

 A recording of this presentation is available HERE.

Check back for a written summary!

Anticoagulation (Nguyen, 12/10/2025)

 A recording of this presentation is available HERE.

***

Thanks to Dr. Bao Chau Nguyen for a great review of Anticoagulation this week, with a quick review of warfarin, heparin/LMWH, and a particular focus on the Direct Oral Anticoagulants (DOACs), which have become the mainstay of anticoagulation. 

Dr. Nguyen reminded us of the current 2025 indications for Vitamin K antagonist (warfarin), which have dwindled to three at this point

• mechanical heart valves
• atrial fibrillation with mod/severe mitral stenosis (esp rheumatic disease)
• antiphospholipid syndrome (APLS)

She also reminded us of the many challenges with Vit K antagonists, which include frequent monitoring, drug-food interactions, and drug-drug interactions.

Current indications for DOACs as first line:

• non-valvular Afib
• treatment of VTE (DVT/PE)
• prevention of VTE (extended)
• select stable PAD/CAD

Summary of indication and dosing of available DOACs:

Dabigatran

• AF: 150 mg BID, reduce to 110 mg BID (age >80, high bleed risk, interacting drugs), Avoid if CrCl <30 (varies by region)
• VTE: 5 days parenteral therapy, then 150 mg BID, 110 mg BID if elderly or high bleeding risk

Apixaban

• AF (stroke prevention): 5 mg BID, Reduce to 2.5 mg BID if ≥2 of the following: Age ≥ 80, Weight ≤ 60 kg, Creatinine ≥ 1.5 mg/dL (or CrCl <30–50 depending on guideline nuance)
• VTE: 10 mg BID x7 days, then 5 mg BID
•  Extended therapy (>6-12 months): 2.5 mg BID

Rivaroxaban

• AF: 20 mg once daily with food, reduce to 15 mg daily if CrCl 15–49 ml/min
• VTE: 15 mg BID x21 days, then 20 mg daily with food

Edoxaban

• AF: 60 mg daily, reduce to 30 mg daily if CrCl 15–50, Weight ≤ 60 kg, certain P-gp inhibitors
• VTE: 5 days of initial parenteral anticoagulation, then 60 mg daily (or 30 mg if meeting criteria above)

Reversal agents for DOACs:

Factor Xa inhibitors (Apixaban, Rivaroxaban, Edoxaban): Andexanet alfa (preferred when available), 4-factor PCC 50 units/kg if andexanet unavailable

Dabigatran: Idarucizumab 5 g IVAdjuncts: tranexamic acid, local control, supportive care.

There are now practice guidelines for pausing and restarting DOAC in setting of non-urgent surgery

Finally, Dr. Nguyen presented three important 2025 updates on DOACs:

1) DOAC vs. warfarin in CKD patients (SCr<25), a metanalysis of >71K patients with Atrial fibrillation and CKD, which found that standard dose of DOAC compared to warfarin showed decrease risk of CVA, systemic embolism and ICH, with similar risk of bleeding. HOWEVER, inappropriate dose reduction of DOAC resulted in increased risk of CVA and death. Take home: DOACs are safe and effective in patients with AFib and decreased GFR but should be regular/full dose. 

https://www.jabfm.org/content/early/2025/01/16/jabfm.2024.240155R0?utm_source=chatgpt.com

2) DOAC for patients with BMI >50: retrospective cohort study of 754 patients that compared DOAC to warfarin and found a non-statistically significant trend toward favoring DOAC (outcomes CVA, all cause mortality, major bleeding). Take home: DOACs are probably better than warfarin for morbidly obese patients with BMI>50.

https://www.sciencedirect.com/science/article/pii/S240584402417627X?utm_source=chatgpt.com

3) Reduced dosage of DOAC in extended treatment of VTE: systematic review and metanalysis of 5 RCTs looking at recurrent VTE, major bleeding. Found no significant increase in recurrent VTE between reduced vs. full dose, significantly lower bleeding risk in reduced dose group. Take home: It appears safe and effective to reduce DOAC to half dose after treating for acute VTE (usually 6 months). 

https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1708316/full?utm_source=chatgpt.com

Family Communication in Palliative Care (Wagner, 12/3/2025)

 A recording of this presentation is available HERE.

***

Thanks to Dr. Andrew Wagner, who gave a really thoughtful and important Grand Rounds this week entitled, Palliative Care Pearls. He spent the bulk of the time showering us with pearls about how to connect and communicate with patients, particularly at the end of life. He touched on spirituality in medicine and lifted up the notion that good communication is good medicine. The sound quality on the recording isn't excellent, but still is worth watching so that you can experience directly his wisdom and experience.

I highlighted the key pearly questions in bold below. 

He highlighted listening and relationship, generous listening, and presence/compassion/empathy. He talked about how death is a part of the life cycle (not a failure) and that healing is coming to peace with mind, body, and soul relationships with spirits on a higher power. If we reframe death as a life cycle event, we can help patients find peace.

One question: "What needs to happen so you can lay your head on your pillow, and say 'I am good'?"

Dr. Wagner talked extensively about centering the patient's identity, values and meaning, which lends itself toward shared decision making: align decisions with values and what matters most, explore "what are you hoping for and what are you most worried about"?, present options in terms of burdens and benefits, and ensure patient and family understand prognosis realistically.

We have the opportunity to offer "a sense of calm", which can be achieved by making eye contact, touch (if/when appropriate), reading the room, modulating voice, sitting down (and ensuring everyone has a chair), arranging the room. 

Another possible question: "How are you doing? How is this going for you?"

Imagine if we regarded death as a final stage of growth. Could we then turn toward death as a master teacher and ask "How then shall I live?"

A third question: "What do you know about what the doctors have been telling you?"

Normalize things for patients, "most people in your situations are anxious/fearful-- how are you doing?", OR "Many people are afraid of dying, is that you?"

Palliative care is understanding people's values and goals and creating care plans that are consistent with those values and goals. Everyone gets tired and frustrated with serious illness, but if someone is feeling that way consistently, "it's important for you to tell us that because there are care plans for people who are tired of doing those things". 

When dealing with surrogate decision makers, it is extremely important to help the surrogate bring the patient into the room: Tell us about [Joe]. Who was he? What did he love? What made him happy? What was important to him?

A fourth question: "Imagine [Joe] had a crystal ball and could hear all the things we have been talking about; what would [Joe] say?". And then a follow-up once you have elicited Joe's ideals, "I recommend, given what we know about what [Joe] cares about, I recommend . . ." (is this consistent/not consistent with Joe's values.

Dr. Wagner reminded us that physicians can and should be more directive when it comes to Code/CPR decisions.

And when it comes to families that do not want information disclosed to patients, try this fifth question: "I understand you don't want me to tell grandma, but is it okay if I ask grandma if she wants to know more about what is going on?"

Lean into the mystery. Nobody knows.

He also reminded us about self care-- I am enough (see below) and I am not alone (we have teammates, colleagues, chaplains, pastoral consultation), and we should be sharing stories as a means of self-healing.

For those of you interested in the resources he references, here are some:

• Rachel Naomi Remen, MD (Kitchen Table Wisdom and My Grandfather's Blessings) "Healing and the Inner Life: The role of clinician is witnessing>> connection>>healing
• "I am enough" (this he lifted up as important to physicians to remember and recite before stepping into challenging situations. We meet patients AS THEY ARE; our presence is enough"
• "All healing is mutual" (physicians are also healed by the encounter)
• Generous listening-- listening to understanding, NOT fixing, the quality of listening 
• Blessing each other-- seeing wholeness beneath illness
• Ira Byock, MD "The Four Things:
• Please forgive me
• I forgive you
• Thank you
• I love you
• Balfour Mount, MD "Human Question": What would you want me to know that will allow me to give you excellent care?
• Harvey Chochinov, MD, "Dignity Therapy"
• continuity of self: "What do you most want remembered about you?"
• role preservation
• generativity
• hopefulness

Finally, some clinician take-aways: 1) holding safe space 2) healing at the end of life 3) honoring intuation and wisdom ("trust your gut, your intuition, your wisdom"). A final useful statement: "We are helping [Joe] to die".

Tumor Lysis Syndrome (Truong, 11/19/2025)

 Thanks so much to our Pharmacy Resident, Lam Truong, who gave an excellent Grand Rounds this week on Tumor Lysis Syndrome.

Recording will be posted HERE when available. 

In the meantime, enjoy the cliff notes (thanks Cherie Green!)

Tumor Lysis Syndrome

• Oncological emergency from rapid breakdown of malignant cells leading to massive release of intracellular contents into bloodstream
• Overall in hospital mortality is 21%
• Most common in NHL(30%) > solid tumors (20%) > AML (19%)> ALL (13%)
• TLS can either present at initial dx with very aggressive tumors (usually lymphomas/leukemias but occasional very aggressive solid tumors), OR onset can be 3-7 days after chemotherapy - so patients with upcoming chemotherapy get labs 3 days prior to chemotherapy both to make sure they are not already in TLS and to compare post-chemo labs

Diagnosis: Prompt recognition and tx are essential….

4 Lab abnormalities for dx: 

Hyperkalemia (tumor cell lysis), Hyperphosphatemia (cell lysis), Hyperuricemia (from breakdown of DNA/RNA-crystal nephropathy), and Hypocalcemia (binds the excess phosphate)

Result:AKI (uric acid crystals, direct cytotoxicity), cardiac arrhythmias (hyperK), and seizures (metabolic disturbances), neuromuscular dysfunction (rigidity)

Symptoms: n/v/d, weakness, muscle cramps, paresthesias, seizures, arrhythmia, hypotension, HF, syncope, oliguria, hematuria, edema, joint pain - so keep your differential broad if patients present with these sxs!

Causes: chemo causing cytotoxic effects, molecular targeted therapies and immunotherapies, can occur spontaneously in setting of large tumor burden even in absence of treatment initiation

Monitor Uric acid, K Phos, Ca, Cr, LDH (high LDH represents rapid cell turnover)

Prevention of Tumor Lysis Syndrome:

Hydration protocol, closely monitor UO, dc nephrotoxins, stop all K agents 

Hypouricemic Agents for prevention and tx

Allopurinol xanthine oxidase inhibitor used in intermediate risk patients, prophylaxis in TLS but has slower onset than…

Rasburicase recombinant urate oxidase inhibitor for high risk patients and tx of active hyperuricemia works rapidly (risks: hemolytic anemia in G6PD deficiency). Loading dose 3 mg IV x 1 

Management: Use Tumor Lysis Order Set 

• Look at criteria and lab monitoring - some need additional doses of rasburicase and q6 hr labs
• HyperK: use protocol
• Hyperphos: treat first with binders and concurrently treat hypocalcemia
• HypoCa: look on the line above, don't treat first. Treat Phos first!
• HD for usual indications (refractory hyperK, fluid overload, etc)

Disability in Medicine (Lindsay, 11/5/2025)

 A recording of this presentation is available HERE.

Acute Liver Injury (Deis, 10/29/25)

 A recording of this presentation is available HERE.

Many thanks to Dr. Faith Deis for an awesome presentation this week on Acute Liver Injury (ALI). For those impatient folks out there, the most important take home points are: 

1) While the combination of alcohol and acetaminophen can actually be hepato-protective, a pattern of heavy ETOH use + fasting followed by moderate to high dose of APAP can be particularly hepatotoxic and make vulnerable patients more susceptible to ALI. 

2) N-Acetylcysteine (NAC) replenishes glutathione with is hepatoprotective and shows benefit for ALI of multiple etiologies (not just APAP intoxication); when in doubt and/or when in the midst of a work-up, give NAC empirically for any undifferentiated ALI, even if APAP level is normal.

A few more pearls from Dr. Deis's talk follow. . .

Acute Liver Failure= Acute liver injury (as indicated by elevation in AST/ALT) + Coagulopathy (INR>1.5) + Hepatic Encephalopathy

Much like many of us use LactMed for breastfeeding safety, there is an excellent NIH source, LiverTox, which compiles all the evidence we have on liver toxicity of medications. Just last night while precepting, a resident and I used this resource to understand whether GLP-1 medications may be implicated in rising transaminases in a patient with poorly controlled DM2. This is a great resource!

Dr. Deis introduced us to the idea of using the "R factor" to help distinguish between intrahepatic and cholestatic patterns of liver injury.

From the 2021 ACG Guidelines. You can see how both the LiverTox and the R factor are involved in your clinical decision about 1st line testing for abnormal liver enzymes:

A little physiology and pathophysiology of APAP Toxicity, which you will note involves the CYP-2E1 pathway (5-9% of hepatic metabolism of APAP) and NAPQI, which leads to hepatocyte necrosis. In APAP overdose, more of the pathway is pushed to the NAPQI pathway! This is important in consideration the mechanism of action of NAC, which actually helps to replenish glutathione, and therefore shift the ASAP metabolism pathway away from the toxic one and back to the healthy one.

Dr. Deis also shared an interesting set of studies on the interaction between APAP and Alcohol on liver metabolism. This is super interesting! It turns out that if APAP and alcohol are ingested simultaneously, alcohol's metabolism actually has a protective effect on the liver's metabolism of APAP, keeping it in the non-toxic pathway. BUT if alcohol is ingested prior to APAP administration (and particularly in the setting of prolonged fasting, which is not uncommon during an alcohol binge), then the use of APAP is pushed toward the NAPQI pathway and is more likely to be hepatotoxic. Practically speaking, then, if a patient has an alcohol binge, and then consumes even moderate doses of APAP at the tail end/after the binge, those moderate doses may lead to a disproportionately toxic impact on the liver. This means, then, that you can have acute liver injury (and even failure) from a therapeutic dose of APAP. 

What about NAC?

Turns out that NAC's protective effect on the liver extends beyond APAP ingestion. In a 2021 Metanalysis , authors found a small but stastitically significant mortality benefit in patients with non-APAP induced liver injury and improved mortality (see table below). There are actually few downsides to NAC (the only absolute contraindication is allergy to NAC itself, care with volume needed to infuse for patients for whom volume could be problematic). In sum,  American College of Gastroenterology 2024 Guidelines actually recommend NAC be administered to all patients with ALI while work-up is in progress. 

A bit on Alcoholic Hepatitis (which may be on your ddx in someone with binge drinking behaviors)

-Remember the Alcoholic hepatitis rarely has AST/ALT elevated above 400-500 and the AST/ALT ratio should be somewhere around 1.5 and the Total Bilirubin is almost always >3.

The 2024 ACG guidelines on alcohol associated liver disease have a really nice set of flowsheets (for those of you who love flowsheets) that nicely outline the evaluation of Alcoholic hepatitis and the subsequent decision tree around using (or not using) steroids, remembering that steroids have downsides (infection, GI bleed, hyperglycemia, AKI, psych) and should only be used in appropriate candidates. 

 

On a final note, we must be careful with patients with ALI who also undergo alcohol withdrawal. Phenobarbital, which has become widely used in our institution in the last year, is relatively contraindicated, as are sedating medications (e.g. benzos). That being said, alcohol withdrawal is a dangerous condition that could result in ICU transfer and/or even death, so we need to be treating them. A reminder that librium/chlordiazepoxide, which has widely fallen out of favor, may be the best option in these patients. 

So much good learning!

Thanks for making it to the end.

Dr. Deis' references:

ACG Guidelines 2024

LiverTox

AASLD

Ghosh, A., Berger, I., & Remien, C. H. (2020). The role of alcohol consumption on acetaminophen-induced liver injury: Implications from a mathematical model. Journal of Theoretical Biology, 510, 110559. https://doi.org/10.1016/j.jtbi.2020.110559 ouci.dntb.gov.ua+1

Forget, P., Wittebole, X., & Laterre, P.-F. (2009). Therapeutic dose of acetaminophen may induce fulminant hepatitis in the presence of risk factors: A report of two cases. British Journal of Anaesthesia, 103(6), 899-900. https://doi.org/10.1093/bja/aep322 OUP Academic

Ghosh, A., Berger, I., Remien, C. H., & Mubayi, A. (2020). The role of alcohol consumption on acetaminophen-induced liver injury: Implications from a mathematical model. Journal of Theoretical Biology, 510, 110559. https://doi.org/10.1016/j.jtbi.2020.110559. (Note: duplicate to #1 – keep one)

Lee, W. M., Kaplowitz, N., et al. (2020). Acute liver injury with therapeutic doses of acetaminophen (≤ 6 g/day): A prospective study. Hepatology, (in press). https://pubmed.ncbi.nlm.nih.gov/33306215/ PubMed+1

Whitcomb, D. C., & Block, G. D. (1994). Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA, 272(23), 1845-1850. https://doi.org/10.1001/jama.272.23.1845 (from PubMed 7990219)

Alzheimer's Disease 2025 (Mendius 10/15/2025)

 A recording of this presentation is available HERE.

***

Thanks to Dr. Mendius, SMGR Neurologist, for a practice-changing Grand Rounds presentation on Alzheimer's Disease (AD) in 2025. Dr. Mendius shared that he had updated this presentation from 2022, and whereas in 2022, he was filled cynicism and despair regarding the diagnosis and treatment of AD, just three years later, he is filled (and filled us) with tremendous hope. 

Gosh, don't we all need a little more hope these days?! Well. . .here it is, in the form of GR notes on AD!

Two important primary care practice changers right up front:

• Primary care providers should be ordering a serum blood test  for diagnostics-- Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio -- for patients with cognitive impairment and in whom you suspect Alzheimer's Disease
• Primary care providers should refer ALL patients with cognitive impairment/concern for dementia to neurology for assessment for new anti-amyloid treatments if they meet indications

 Major neurocognitive disorder criteria

• Acquired
• disabling decline from prior level of function (be aware that if you are declining from a relatively high level of function, you may still have a significant dementia)
• single cognitive area sufficient

Cognitive domains

• learning and memory (ability to acquire, store, recall info)
• language (comprehend, repeat, produce in reading/writing/speaking)
• executive function (plan for something, e.g. get to store and back with all the things)
• complex attention (sustained focus/attention on something, divided attention)
• perceptual motor (take a visual, auditory or tactile stimulus and make a complex response)
• social cognition (can you process social cues, appropriateness of their and your own behavior, theory of mind-- understand their processes)

Ddx of Dementia

• Alzheimer 60-80% (most common by far)
• Vascular 15-20% 
• Lewy Body 10%
• Frontotemporal 2-10%
• Parkinson's Dementia 2%
• Mixed 10%
• Other: Huntington, CJD, CTE 

Life Expectancy: at age of 70, 3-10 years at time of diagnosis. Average is 7 in AD, but 6-20 years is what Dr. Mendius quotes to patients. 

"Reversible" Dementias: Alcohol, Depression, Metabolic (Thyroid, Parathyroid, B12/folate), Infectious (HIV, syphilis, long COVID), Structural (NPH, subdural hematoma, tumor)

Top Score=30, 26 is lower limit of normal

Dr. Mendius prefers the MOCA due to combination of executive function, language function, visuospatial function and memory. Formal neuropsych testing costs thousands of dollars and 2 days of work. Comprehensive Dementia Review (CDR) is used a lot in research studies but not used much in clinic. 

A few pearls on Parkinsonism and Dementia

• Parkinson's Disease (PD) has significant dementia component, 40-60% of PD patients "dement" during the course of their disease
• There is an important difference between Lewy Body Dementia and PD Dementia>>stiffness/tremor/slowness/postural instability presents WITH the dementia at time of  onset. Also presents with REM sleep, visual hallucinations, vivid dreams. 
• In PD, dementia presents late, 5-8 years after the onset of tremor/movement disorder

Mild Cognitive Impairment: 20% of population >70 has MCI. Most will remain stable, about 25-40% progress to dementia (10-15% per year). People with MCI presenting with primarily short term memory group is most likely to progress to AD

RF: age, smoking, obesity, lack of exercise

Alzheimer's Disease

Genetic Autosomal Dominant occurs in  <1% of AD, mutation amyloid precursor

Only 7.5% of AD presentation presents <65 years (some genetics, some non-genetics)

Cardinal features of AD:

• Memory impairment-- generally begins with declarative episodic memory (time/place) BEFORE semantic and procedural memories. Anterograde long term episodic amnesia. Trouble laying down new memories. In MOCA task, give 5 words to remember>> if unable to recall words with hints indicate more significant Alzheimer pathology
• Executive functioning-- anosognosia "I don't know I have a problem" (If someone comes in worried about their memory, they usually don't have dementia, if their spouse is worried>> more likely to be a problem)
• Visuospatial impairment: ability to draw cube, numbers on clock
• Language difficulties: "like pruning a tree", language becomes very simple, words to describe things begin to disappear, circumlocution (talk all around a word to describe something)
• Behavioral Symptoms: apathy and social disengagement, irritability/wandering/aggression tend to be late. Capgras phenomenon: "this is not my wife"
• Apraxia: motor tasks, e.g. show me how you brush your teeth, use a razor to shave
• Olfactory dysfunction is typically late
• Sleep disturbance: frequent arousal
• Seizures 10-20% of patients with AD have seizures
• Motor: myoclonus, frontal release signs late in the course

Neuroimaging reveals specific atrophy patterns:

Alzheimer Molecular Biomarkers

• Currently studying and targeting amyloid and tau, microglia
• NEW this year!!!! Lumipulse G pTau217/ß-Amyloid 1-42 Plasma Ratio (17970) is a serum test that is sufficiently diagnostic for AD, some pretty good numbers: 91% positive predictive value and 95% negative predictive value (Palmquist 2025). You can reduce the "indeterminate population" down to about 10%. Seems to be covered by insurance!
• Can be used in the amnestic/MCI population
• This test should not be done on a "normal" (i.e. not cognitively impaired) patient
• Lumipulse is necessary to get into trials for antibody infusions

Amyloid is in the brain for a reason>> part of the innate immune system, involved in synaptic formation and repair, organizing long term memory and synaptic organization, also involved in moving things from cell bodies into dendrite and axons

There are TWO Current anti amyloid antibodies that are available:

1) Lecanemab: against protofibrils, used in MCI and mild AD dementia, 10mg/kg every other week. Infusion reactions are common 26% (need to watch 4 hours after first three infusions). need frequently MRI scans to look for flare/T2 for edema, hemorrhage and hemosiderin (12-17% of patients, most asymptomatic, but 9/900 had significant hemorrhage)

-Efficacy demonstrated in study of  1800 patients, 18 months, outcome: CDR, 30% slowing of decline, marked reduction of amyloid in the brain, improvement best if amyloid reduced to 15-20% of what you expect in AD population. Efficacy is maintained to a couple of years for those who respond. NEW Subq injection (weekly) just approved. 

2) Donanemab: goes against deposited plaques, this is a monthly injection, need frequent MRIs

-Efficacy : similar to Lecanemab -- 30% slowing in decline, side effects: 24% edema, hemorrhage/hemosiderin in 30% (vs. 13% in placebo arm)

FUTURE????

Tau seems like major target we will be treating in the future>> tau stabilizes microtubule bundles (internal cytoskeleton of the neuron). Also involved in transport functions. Functional tau has a specific distribution, pathologic tau clumps and destabilizes the microtubule>> neurofibrillary tangle. Stages of AD seem related to Tau.

Microglia also seems like future possibility>> microglia is brain's immune system (lymphocyte infiltrated into the tissue)

170 drugs in various stages of development!

Lifetime interventions for dementia prevention: see the Lancet image below: ~30-40% of dementia is preventable over a lifetime.

2024 Lancet standing commission