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extacy
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sadism
sadismed
sadismer
sadismes
sadisming
sadismly
sadisms
sadist
sadisted
sadister
sadistes
sadisting
sadistly
sadists
scag
scaged
scager
scages
scaging
scagly
scags
scantily
scantilyed
scantilyer
scantilyes
scantilying
scantilyly
scantilys
schlong
schlonged
schlonger
schlonges
schlonging
schlongly
schlongs
scrog
scroged
scroger
scroges
scroging
scrogly
scrogs
scrot
scrote
scroted
scroteed
scroteer
scrotees
scroteing
scrotely
scroter
scrotes
scroting
scrotly
scrots
scrotum
scrotumed
scrotumer
scrotumes
scrotuming
scrotumly
scrotums
scrud
scruded
scruder
scrudes
scruding
scrudly
scruds
scum
scumed
scumer
scumes
scuming
scumly
scums
seaman
seamaned
seamaner
seamanes
seamaning
seamanly
seamans
seamen
seamened
seamener
seamenes
seamening
seamenly
seamens
seduceed
seduceer
seducees
seduceing
seducely
seduces
semen
semened
semener
semenes
semening
semenly
semens
shamedame
shamedameed
shamedameer
shamedamees
shamedameing
shamedamely
shamedames
shit
shite
shiteater
shiteatered
shiteaterer
shiteateres
shiteatering
shiteaterly
shiteaters
shited
shiteed
shiteer
shitees
shiteing
shitely
shiter
shites
shitface
shitfaceed
shitfaceer
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shitfaceing
shitfacely
shitfaces
shithead
shitheaded
shitheader
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shitheading
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shitheads
shithole
shitholeed
shitholeer
shitholees
shitholeing
shitholely
shitholes
shithouse
shithouseed
shithouseer
shithousees
shithouseing
shithousely
shithouses
shiting
shitly
shits
shitsed
shitser
shitses
shitsing
shitsly
shitss
shitt
shitted
shitteded
shitteder
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shitteding
shittedly
shitteds
shitter
shittered
shitterer
shitteres
shittering
shitterly
shitters
shittes
shitting
shittly
shitts
shitty
shittyed
shittyer
shittyes
shittying
shittyly
shittys
shiz
shized
shizer
shizes
shizing
shizly
shizs
shooted
shooter
shootes
shooting
shootly
shoots
sissy
sissyed
sissyer
sissyes
sissying
sissyly
sissys
skag
skaged
skager
skages
skaging
skagly
skags
skank
skanked
skanker
skankes
skanking
skankly
skanks
slave
slaveed
slaveer
slavees
slaveing
slavely
slaves
sleaze
sleazeed
sleazeer
sleazees
sleazeing
sleazely
sleazes
sleazy
sleazyed
sleazyer
sleazyes
sleazying
sleazyly
sleazys
slut
slutdumper
slutdumpered
slutdumperer
slutdumperes
slutdumpering
slutdumperly
slutdumpers
sluted
sluter
slutes
sluting
slutkiss
slutkissed
slutkisser
slutkisses
slutkissing
slutkissly
slutkisss
slutly
sluts
slutsed
slutser
slutses
slutsing
slutsly
slutss
smegma
smegmaed
smegmaer
smegmaes
smegmaing
smegmaly
smegmas
smut
smuted
smuter
smutes
smuting
smutly
smuts
smutty
smuttyed
smuttyer
smuttyes
smuttying
smuttyly
smuttys
snatch
snatched
snatcher
snatches
snatching
snatchly
snatchs
sniper
snipered
sniperer
sniperes
snipering
sniperly
snipers
snort
snorted
snorter
snortes
snorting
snortly
snorts
snuff
snuffed
snuffer
snuffes
snuffing
snuffly
snuffs
sodom
sodomed
sodomer
sodomes
sodoming
sodomly
sodoms
spic
spiced
spicer
spices
spicing
spick
spicked
spicker
spickes
spicking
spickly
spicks
spicly
spics
spik
spoof
spoofed
spoofer
spoofes
spoofing
spoofly
spoofs
spooge
spoogeed
spoogeer
spoogees
spoogeing
spoogely
spooges
spunk
spunked
spunker
spunkes
spunking
spunkly
spunks
steamyed
steamyer
steamyes
steamying
steamyly
steamys
stfu
stfued
stfuer
stfues
stfuing
stfuly
stfus
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stiffyed
stiffyer
stiffyes
stiffying
stiffyly
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stoneder
stonedes
stoneding
stonedly
stoneds
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stupider
stupides
stupiding
stupidly
stupids
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suckeder
suckedes
suckeding
suckedly
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sucker
suckes
sucking
suckinged
suckinger
suckinges
suckinging
suckingly
suckings
suckly
sucks
sumofabiatch
sumofabiatched
sumofabiatcher
sumofabiatches
sumofabiatching
sumofabiatchly
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tard
tarded
tarder
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tarding
tardly
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tawdryed
tawdryer
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tawdrying
tawdryly
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teabagginged
teabagginger
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teabagginging
teabaggingly
teabaggings
terd
terded
terder
terdes
terding
terdly
terds
teste
testee
testeed
testeeed
testeeer
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testeeing
testeely
testeer
testees
testeing
testely
testes
testesed
testeser
testeses
testesing
testesly
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testicle
testicleed
testicleer
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testicleing
testiclely
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testised
testiser
testises
testising
testisly
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thrusted
thruster
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thrusting
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thuger
thuges
thuging
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tinkleed
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tinkleing
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tit
tited
titer
tites
titfuck
titfucked
titfucker
titfuckes
titfucking
titfuckly
titfucks
titi
titied
titier
tities
titiing
titily
titing
titis
titly
tits
titsed
titser
titses
titsing
titsly
titss
tittiefucker
tittiefuckered
tittiefuckerer
tittiefuckeres
tittiefuckering
tittiefuckerly
tittiefuckers
titties
tittiesed
tittieser
tittieses
tittiesing
tittiesly
tittiess
titty
tittyed
tittyer
tittyes
tittyfuck
tittyfucked
tittyfucker
tittyfuckered
tittyfuckerer
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tittyfuckering
tittyfuckerly
tittyfuckers
tittyfuckes
tittyfucking
tittyfuckly
tittyfucks
tittying
tittyly
tittys
toke
tokeed
tokeer
tokees
tokeing
tokely
tokes
toots
tootsed
tootser
tootses
tootsing
tootsly
tootss
tramp
tramped
tramper
trampes
tramping
tramply
tramps
transsexualed
transsexualer
transsexuales
transsexualing
transsexually
transsexuals
trashy
trashyed
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trashyes
trashying
trashyly
trashys
tubgirl
tubgirled
tubgirler
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tubgirling
tubgirlly
tubgirls
turd
turded
turder
turdes
turding
turdly
turds
tush
tushed
tusher
tushes
tushing
tushly
tushs
twat
twated
twater
twates
twating
twatly
twats
twatsed
twatser
twatses
twatsing
twatsly
twatss
undies
undiesed
undieser
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undiesing
undiesly
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unweder
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unwedly
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uzied
uzier
uzies
uziing
uzily
uzis
vag
vaged
vager
vages
vaging
vagly
vags
valium
valiumed
valiumer
valiumes
valiuming
valiumly
valiums
venous
virgined
virginer
virgines
virgining
virginly
virgins
vixen
vixened
vixener
vixenes
vixening
vixenly
vixens
vodkaed
vodkaer
vodkaes
vodkaing
vodkaly
vodkas
voyeur
voyeured
voyeurer
voyeures
voyeuring
voyeurly
voyeurs
vulgar
vulgared
vulgarer
vulgares
vulgaring
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vulgars
wang
wanged
wanger
wanges
wanging
wangly
wangs
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wanked
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wankering
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wankes
wanking
wankly
wanks
wazoo
wazooed
wazooer
wazooes
wazooing
wazooly
wazoos
wedgie
wedgieed
wedgieer
wedgiees
wedgieing
wedgiely
wedgies
weeded
weeder
weedes
weeding
weedly
weeds
weenie
weenieed
weenieer
weeniees
weenieing
weeniely
weenies
weewee
weeweeed
weeweeer
weeweees
weeweeing
weeweely
weewees
weiner
weinered
weinerer
weineres
weinering
weinerly
weiners
weirdo
weirdoed
weirdoer
weirdoes
weirdoing
weirdoly
weirdos
wench
wenched
wencher
wenches
wenching
wenchly
wenchs
wetback
wetbacked
wetbacker
wetbackes
wetbacking
wetbackly
wetbacks
whitey
whiteyed
whiteyer
whiteyes
whiteying
whiteyly
whiteys
whiz
whized
whizer
whizes
whizing
whizly
whizs
whoralicious
whoralicioused
whoraliciouser
whoraliciouses
whoraliciousing
whoraliciously
whoraliciouss
whore
whorealicious
whorealicioused
whorealiciouser
whorealiciouses
whorealiciousing
whorealiciously
whorealiciouss
whored
whoreded
whoreder
whoredes
whoreding
whoredly
whoreds
whoreed
whoreer
whorees
whoreface
whorefaceed
whorefaceer
whorefacees
whorefaceing
whorefacely
whorefaces
whorehopper
whorehoppered
whorehopperer
whorehopperes
whorehoppering
whorehopperly
whorehoppers
whorehouse
whorehouseed
whorehouseer
whorehousees
whorehouseing
whorehousely
whorehouses
whoreing
whorely
whores
whoresed
whoreser
whoreses
whoresing
whoresly
whoress
whoring
whoringed
whoringer
whoringes
whoringing
whoringly
whorings
wigger
wiggered
wiggerer
wiggeres
wiggering
wiggerly
wiggers
woody
woodyed
woodyer
woodyes
woodying
woodyly
woodys
wop
woped
woper
wopes
woping
woply
wops
wtf
wtfed
wtfer
wtfes
wtfing
wtfly
wtfs
xxx
xxxed
xxxer
xxxes
xxxing
xxxly
xxxs
yeasty
yeastyed
yeastyer
yeastyes
yeastying
yeastyly
yeastys
yobbo
yobboed
yobboer
yobboes
yobboing
yobboly
yobbos
zoophile
zoophileed
zoophileer
zoophilees
zoophileing
zoophilely
zoophiles
anal
ass
ass lick
balls
ballsac
bisexual
bleach
causas
cheap
cost of miracles
cunt
display network stats
fart
fda and death
fda AND warn
fda AND warning
fda AND warns
feom
fuck
gfc
humira AND expensive
illegal
madvocate
masturbation
nuccitelli
overdose
porn
shit
snort
texarkana
Bipolar depression
Depression
adolescent depression
adolescent major depressive disorder
adolescent schizophrenia
adolescent with major depressive disorder
animals
autism
baby
brexpiprazole
child
child bipolar
child depression
child schizophrenia
children with bipolar disorder
children with depression
children with major depressive disorder
compulsive behaviors
cure
elderly bipolar
elderly depression
elderly major depressive disorder
elderly schizophrenia
elderly with dementia
first break
first episode
gambling
gaming
geriatric depression
geriatric major depressive disorder
geriatric schizophrenia
infant
kid
major depressive disorder
major depressive disorder in adolescents
major depressive disorder in children
parenting
pediatric
pediatric bipolar
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A peer-reviewed clinical journal serving healthcare professionals working with the Department of Veterans Affairs, the Department of Defense, and the Public Health Service.
Brain Cancer: Epidemiology, TBI, and New Treatments
Brain Cancer: Epidemiology, TBI, and New Treatments
Click to view more from Cancer Data Trends 2025.
- Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182 - Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588 - DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
2024. https://researchbraininjury.org/ - Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312 - Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(e100042. doi:10.1200/EDBK_100042 - Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
doi:10.1038/s41467-024-51332-7 - Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
2023;389(7):589-601. doi:10.1056/NEJMoa2304194 - FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
susceptible-idh1-or-idh2-mutation - NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf - The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
docs/surveysandstudies/vetpop.pdf - Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
doi:10.1093/neuonc/noac035
Click to view more from Cancer Data Trends 2025.
Click to view more from Cancer Data Trends 2025.
- Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182 - Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588 - DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
2024. https://researchbraininjury.org/ - Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312 - Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(e100042. doi:10.1200/EDBK_100042 - Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
doi:10.1038/s41467-024-51332-7 - Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
2023;389(7):589-601. doi:10.1056/NEJMoa2304194 - FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
susceptible-idh1-or-idh2-mutation - NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf - The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
docs/surveysandstudies/vetpop.pdf - Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
doi:10.1093/neuonc/noac035
- Bihn JR, Cioffi G, Waite KA, et al. Brain tumors in United States military veterans.
Neuro Oncol. 2024;26(2):387-396. doi:10.1093/neuonc/noad182 - Stewart IJ, Howard JT, Poltavsky E, et al. Traumatic Brain Injury and Subsequent
Risk of Brain Cancer in US Veterans of the Iraq and Afghanistan Wars. JAMA Netw
Open. 2024;7(2):e2354588. doi:10.1001/jamanetworkopen.2023.54588 - DoD/USU Brain Tissue Repository. December 15, 2023. Accessed December 11,
2024. https://researchbraininjury.org/ - Munch TN, Gørtz S, Wohlfahrt J, Melbye M. The long-term risk of malignant
astrocytic tumors after structural brain injury--a nationwide cohort study. Neuro
Oncol. 2015;17(5):718-724. doi:10.1093/neuonc/nou312 - Strowd RE, Dunbar EM, Gan HK, et al. Practical guidance for telemedicine use in
neuro-oncology. Neurooncol Pract. 2022;9(2):91-104. doi:10.1093/nop/npac002 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(e100042. doi:10.1200/EDBK_100042 - Batool SM, Escobedo AK, Hsia T, et al. Clinical utility of a blood based assay for
the detection of IDH1.R132H-mutant gliomas. Nat Commun. 2024;15(1):7074.
doi:10.1038/s41467-024-51332-7 - Mellinghoff IK, van den Bent MJ, Blumenthal DT, et al; INDIGO Trial Investigators.
Vorasidenib in IDH1- or IDH2-Mutant Low-Grade Glioma. N Engl J Med.
2023;389(7):589-601. doi:10.1056/NEJMoa2304194 - FDA. US Food and Drug Administration. FDA approves vorasidenib for Grade 2
astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation.
Accessed December 11, 2024. https://www.fda.gov/drugs/resourcesinformation-
approved-drugs/fda-approves-vorasidenib-grade-2-astrocytoma-oroligodendroglioma-
susceptible-idh1-or-idh2-mutation - NIH. National Cancer Institute. Tovorafenib Approved for Some Children with Low-
Grade Glioma. Accessed December 11, 2024. https://www.cancer.gov/news-events/
cancer-currents-blog/2024/pediatric-low-grade-glioma-tovorafenib-braf - The Veteran Population. Accessed December 11, 2024. https://www.va.gov/vetdata/
docs/surveysandstudies/vetpop.pdf - Miller AM, Szalontay L, Bouvier N, et al. Next-generation sequencing of
cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent
and young adult brain tumor patients. Neuro Oncol. 2022;24(10):1763-1772.
doi:10.1093/neuonc/noac035
Brain Cancer: Epidemiology, TBI, and New Treatments
Brain Cancer: Epidemiology, TBI, and New Treatments
AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
Click here to view more from Cancer Data Trends 2025.
1. Zevallos JP, Kramer JR, Sandulache VC, et al. National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System. Head Neck. 2021;43(1):108-115. doi:10.1002/hed.26465
2. Fakhry C, Blackford AL, Neuner G, et al. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019;5(7):985-992. doi:10.1001/jamaoncol.2019.0439
3. Fakhry C, Zhang Q, Gillison ML, et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: implications for risk-based therapeutic intensity trials. Cancer. 2019;125(12):2027-2038. doi:10.1002/cncr.32025
4. O'Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440-451. doi:10.1016/S1470-2045(15)00560-4
5. Koyuncu CF, Lu C, Bera K, et al. Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. J Clin Invest. 2021;131(8):e145488. doi:10.1172/JCI145488
6. Lu C, Lewis JS Jr, Dupont WD, Plummer WD Jr, Janowczyk A, Madabhushi A. An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival. Mod Pathol. 2017;30(12):1655-1665. doi:10.1038/modpathol.2017.98
7. Corredor G, Toro P, Koyuncu C, et al. An imaging biomarker of tumor-infiltrating lymphocytes to risk-stratify patients with HPV-associated oropharyngeal cancer. J Natl Cancer Inst. 2022;114(4):609-617. doi:10.1093/jnci/djab215
8. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute, SEER Program. Accessed November 5, 2024. https://seer.cancer.gov/statfacts/html/oralcav.html
9. Cancers associated with human papillomavirus. Centers for Disease Control and Prevention. September 18, 2024. Accessed November 5, 2024. https://www.cdc.gov/united-states-cancer-statistics/publications/hpv-associated-cancers.html
10. Chidambaram S, Chang SH, Sandulache VC, Mazul AL, Zevallos JP. Human papillomavirus vaccination prevalence and disproportionate cancer burden among US veterans. JAMA Oncol. 2023;9(5):712-714. doi:10.1001/jamaoncol.2022.7944
11. Corredor G, Wang X, Zhou Y, et al. Spatial architecture and arrangement of tumor-infiltrating lymphocytes for predicting likelihood of recurrence in early-stage non-small cell lung cancer. Clin Cancer Res. 2019;25(5):1526-1534. doi:10.1158/1078-0432.CCR-18-2013
12. Alilou M, Orooji M, Beig N, et al. Quantitative vessel tortuosity: a potential CT imaging biomarker for distinguishing lung granulomas from adenocarcinomas. Sci Rep. 2018;8(1):15290. doi:10.1038/s41598-018-33473-0
13. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
Click here to view more from Cancer Data Trends 2025.
Click here to view more from Cancer Data Trends 2025.
1. Zevallos JP, Kramer JR, Sandulache VC, et al. National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System. Head Neck. 2021;43(1):108-115. doi:10.1002/hed.26465
2. Fakhry C, Blackford AL, Neuner G, et al. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019;5(7):985-992. doi:10.1001/jamaoncol.2019.0439
3. Fakhry C, Zhang Q, Gillison ML, et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: implications for risk-based therapeutic intensity trials. Cancer. 2019;125(12):2027-2038. doi:10.1002/cncr.32025
4. O'Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440-451. doi:10.1016/S1470-2045(15)00560-4
5. Koyuncu CF, Lu C, Bera K, et al. Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. J Clin Invest. 2021;131(8):e145488. doi:10.1172/JCI145488
6. Lu C, Lewis JS Jr, Dupont WD, Plummer WD Jr, Janowczyk A, Madabhushi A. An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival. Mod Pathol. 2017;30(12):1655-1665. doi:10.1038/modpathol.2017.98
7. Corredor G, Toro P, Koyuncu C, et al. An imaging biomarker of tumor-infiltrating lymphocytes to risk-stratify patients with HPV-associated oropharyngeal cancer. J Natl Cancer Inst. 2022;114(4):609-617. doi:10.1093/jnci/djab215
8. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute, SEER Program. Accessed November 5, 2024. https://seer.cancer.gov/statfacts/html/oralcav.html
9. Cancers associated with human papillomavirus. Centers for Disease Control and Prevention. September 18, 2024. Accessed November 5, 2024. https://www.cdc.gov/united-states-cancer-statistics/publications/hpv-associated-cancers.html
10. Chidambaram S, Chang SH, Sandulache VC, Mazul AL, Zevallos JP. Human papillomavirus vaccination prevalence and disproportionate cancer burden among US veterans. JAMA Oncol. 2023;9(5):712-714. doi:10.1001/jamaoncol.2022.7944
11. Corredor G, Wang X, Zhou Y, et al. Spatial architecture and arrangement of tumor-infiltrating lymphocytes for predicting likelihood of recurrence in early-stage non-small cell lung cancer. Clin Cancer Res. 2019;25(5):1526-1534. doi:10.1158/1078-0432.CCR-18-2013
12. Alilou M, Orooji M, Beig N, et al. Quantitative vessel tortuosity: a potential CT imaging biomarker for distinguishing lung granulomas from adenocarcinomas. Sci Rep. 2018;8(1):15290. doi:10.1038/s41598-018-33473-0
13. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
1. Zevallos JP, Kramer JR, Sandulache VC, et al. National trends in oropharyngeal cancer incidence and survival within the Veterans Affairs Health Care System. Head Neck. 2021;43(1):108-115. doi:10.1002/hed.26465
2. Fakhry C, Blackford AL, Neuner G, et al. Association of oral human papillomavirus DNA persistence with cancer progression after primary treatment for oral cavity and oropharyngeal squamous cell carcinoma. JAMA Oncol. 2019;5(7):985-992. doi:10.1001/jamaoncol.2019.0439
3. Fakhry C, Zhang Q, Gillison ML, et al. Validation of NRG oncology/RTOG-0129 risk groups for HPV-positive and HPV-negative oropharyngeal squamous cell cancer: implications for risk-based therapeutic intensity trials. Cancer. 2019;125(12):2027-2038. doi:10.1002/cncr.32025
4. O'Sullivan B, Huang SH, Su J, et al. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol. 2016;17(4):440-451. doi:10.1016/S1470-2045(15)00560-4
5. Koyuncu CF, Lu C, Bera K, et al. Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma. J Clin Invest. 2021;131(8):e145488. doi:10.1172/JCI145488
6. Lu C, Lewis JS Jr, Dupont WD, Plummer WD Jr, Janowczyk A, Madabhushi A. An oral cavity squamous cell carcinoma quantitative histomorphometric-based image classifier of nuclear morphology can risk stratify patients for disease-specific survival. Mod Pathol. 2017;30(12):1655-1665. doi:10.1038/modpathol.2017.98
7. Corredor G, Toro P, Koyuncu C, et al. An imaging biomarker of tumor-infiltrating lymphocytes to risk-stratify patients with HPV-associated oropharyngeal cancer. J Natl Cancer Inst. 2022;114(4):609-617. doi:10.1093/jnci/djab215
8. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute, SEER Program. Accessed November 5, 2024. https://seer.cancer.gov/statfacts/html/oralcav.html
9. Cancers associated with human papillomavirus. Centers for Disease Control and Prevention. September 18, 2024. Accessed November 5, 2024. https://www.cdc.gov/united-states-cancer-statistics/publications/hpv-associated-cancers.html
10. Chidambaram S, Chang SH, Sandulache VC, Mazul AL, Zevallos JP. Human papillomavirus vaccination prevalence and disproportionate cancer burden among US veterans. JAMA Oncol. 2023;9(5):712-714. doi:10.1001/jamaoncol.2022.7944
11. Corredor G, Wang X, Zhou Y, et al. Spatial architecture and arrangement of tumor-infiltrating lymphocytes for predicting likelihood of recurrence in early-stage non-small cell lung cancer. Clin Cancer Res. 2019;25(5):1526-1534. doi:10.1158/1078-0432.CCR-18-2013
12. Alilou M, Orooji M, Beig N, et al. Quantitative vessel tortuosity: a potential CT imaging biomarker for distinguishing lung granulomas from adenocarcinomas. Sci Rep. 2018;8(1):15290. doi:10.1038/s41598-018-33473-0
13. Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP. The Eighth Edition AJCC Cancer Staging Manual: Continuing to build a bridge from a population-based to a more "personalized" approach to cancer staging. CA Cancer J Clin. 2017;67(2):93-99. doi:10.3322/caac.21388
AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
AI-Based Risk Stratification for Oropharyngeal Carcinomas: AIROC
Rising Kidney Cancer Cases and Emerging Treatments for Veterans
Rising Kidney Cancer Cases and Emerging Treatments for Veterans
Click here to view more from Cancer Data Trends 2025.
1. American Cancer Society website. Key Statistics About Kidney Cancer. Revised May 2024. Accessed December 18, 2024. https://www.cancer.org/cancer/types/kidney-cancer/about/key-statistics.html
2. American Cancer Society website. Cancer Facts & Figures 2024. 2024—First Year the US Expects More than 2M New Cases of Cancer. Published January 17, 2024. Accessed December 18, 2024. https://www.cancer.org/research/acs-research-news/facts-and-figures-2024.html
3.United States Department of Veterans Affairs factsheet. Pact Act & Gulf War, Post-911 Era Veterans. Published July 2023. Accessed December 18, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.va.gov/files/2023-08/PACT%20Act%20and%20Gulf%20War%2C%20Post-911%20Veterans%20NEW%20July%202023.pdf
4. Li M, Li L, Zheng J, Li Z, Li S, Wang K, Chen X. Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application. Mol Cancer. 2023 Feb 21;22(1):37. doi:10.1186/s12943-023-01745-7
5. Bellman NL. Incidental Finding of Renal Cell Carcinoma: Detected by a Thrombus in the Inferior Vena Cava. Journal of Diagnostic Medical Sonography. 2015;31(2):118-121. doi:10.1177/8756479314546691
6. Brown JT. Adjuvant Therapy for Non-Clear Cell Renal Cell Carcinoma—The Ascent Continues. JAMA Network Open. 2024 Aug 1;7(8):e2425251. doi:10.1001/jamanetworkopen.2024.25251
7. Siva S, Louie AV, Kotecha R, et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS). Lancet Oncol. 2024 Jan;25(1):e18-e28. doi: 10.1016/S1470-2045(23)00513-2.
8. Choueiri TK, Tomczak P, Park SH, et al; for the KEYNOTE-564 Investigators. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359-1371. doi:10.1056/NEJMoa2312695
9. Bytnar JA, McGlynn KA, Kern SQ, Shriver CD, Zhu K. Incidence rates of bladder and kidney cancers among US military servicemen: comparison with the rates in the general US population. Eur J Cancer Prev. 2024 Nov 1;33(6):505-511. doi:10.1097/CEJ.0000000000000886
Click here to view more from Cancer Data Trends 2025.
Click here to view more from Cancer Data Trends 2025.
1. American Cancer Society website. Key Statistics About Kidney Cancer. Revised May 2024. Accessed December 18, 2024. https://www.cancer.org/cancer/types/kidney-cancer/about/key-statistics.html
2. American Cancer Society website. Cancer Facts & Figures 2024. 2024—First Year the US Expects More than 2M New Cases of Cancer. Published January 17, 2024. Accessed December 18, 2024. https://www.cancer.org/research/acs-research-news/facts-and-figures-2024.html
3.United States Department of Veterans Affairs factsheet. Pact Act & Gulf War, Post-911 Era Veterans. Published July 2023. Accessed December 18, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.va.gov/files/2023-08/PACT%20Act%20and%20Gulf%20War%2C%20Post-911%20Veterans%20NEW%20July%202023.pdf
4. Li M, Li L, Zheng J, Li Z, Li S, Wang K, Chen X. Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application. Mol Cancer. 2023 Feb 21;22(1):37. doi:10.1186/s12943-023-01745-7
5. Bellman NL. Incidental Finding of Renal Cell Carcinoma: Detected by a Thrombus in the Inferior Vena Cava. Journal of Diagnostic Medical Sonography. 2015;31(2):118-121. doi:10.1177/8756479314546691
6. Brown JT. Adjuvant Therapy for Non-Clear Cell Renal Cell Carcinoma—The Ascent Continues. JAMA Network Open. 2024 Aug 1;7(8):e2425251. doi:10.1001/jamanetworkopen.2024.25251
7. Siva S, Louie AV, Kotecha R, et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS). Lancet Oncol. 2024 Jan;25(1):e18-e28. doi: 10.1016/S1470-2045(23)00513-2.
8. Choueiri TK, Tomczak P, Park SH, et al; for the KEYNOTE-564 Investigators. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359-1371. doi:10.1056/NEJMoa2312695
9. Bytnar JA, McGlynn KA, Kern SQ, Shriver CD, Zhu K. Incidence rates of bladder and kidney cancers among US military servicemen: comparison with the rates in the general US population. Eur J Cancer Prev. 2024 Nov 1;33(6):505-511. doi:10.1097/CEJ.0000000000000886
1. American Cancer Society website. Key Statistics About Kidney Cancer. Revised May 2024. Accessed December 18, 2024. https://www.cancer.org/cancer/types/kidney-cancer/about/key-statistics.html
2. American Cancer Society website. Cancer Facts & Figures 2024. 2024—First Year the US Expects More than 2M New Cases of Cancer. Published January 17, 2024. Accessed December 18, 2024. https://www.cancer.org/research/acs-research-news/facts-and-figures-2024.html
3.United States Department of Veterans Affairs factsheet. Pact Act & Gulf War, Post-911 Era Veterans. Published July 2023. Accessed December 18, 2024. chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.va.gov/files/2023-08/PACT%20Act%20and%20Gulf%20War%2C%20Post-911%20Veterans%20NEW%20July%202023.pdf
4. Li M, Li L, Zheng J, Li Z, Li S, Wang K, Chen X. Liquid biopsy at the frontier in renal cell carcinoma: recent analysis of techniques and clinical application. Mol Cancer. 2023 Feb 21;22(1):37. doi:10.1186/s12943-023-01745-7
5. Bellman NL. Incidental Finding of Renal Cell Carcinoma: Detected by a Thrombus in the Inferior Vena Cava. Journal of Diagnostic Medical Sonography. 2015;31(2):118-121. doi:10.1177/8756479314546691
6. Brown JT. Adjuvant Therapy for Non-Clear Cell Renal Cell Carcinoma—The Ascent Continues. JAMA Network Open. 2024 Aug 1;7(8):e2425251. doi:10.1001/jamanetworkopen.2024.25251
7. Siva S, Louie AV, Kotecha R, et al. Stereotactic body radiotherapy for primary renal cell carcinoma: a systematic review and practice guideline from the International Society of Stereotactic Radiosurgery (ISRS). Lancet Oncol. 2024 Jan;25(1):e18-e28. doi: 10.1016/S1470-2045(23)00513-2.
8. Choueiri TK, Tomczak P, Park SH, et al; for the KEYNOTE-564 Investigators. Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma. N Engl J Med. 2024 Apr 18;390(15):1359-1371. doi:10.1056/NEJMoa2312695
9. Bytnar JA, McGlynn KA, Kern SQ, Shriver CD, Zhu K. Incidence rates of bladder and kidney cancers among US military servicemen: comparison with the rates in the general US population. Eur J Cancer Prev. 2024 Nov 1;33(6):505-511. doi:10.1097/CEJ.0000000000000886
Rising Kidney Cancer Cases and Emerging Treatments for Veterans
Rising Kidney Cancer Cases and Emerging Treatments for Veterans
Advances in Blood Cancer Care for Veterans
Advances in Blood Cancer Care for Veterans
Click to view more from Cancer Data Trends 2025.
- Li W, ed. The 5th Edition of the World Health Organization Classification of
Hematolymphoid Tumors. In: Leukemia [Internet]. Brisbane (AU): Exon Publications;
October 16, 2022. https://www.ncbi.nlm.nih.gov/books/NBK586208/ - Graf SA, Samples LS, Keating TM, Garcia JM. Clinical research in older adults with
hematologic malignancies: Opportunities for alignment in the Veterans Affairs. Semin
Oncol. 2020;47(1):94-101. doi:10.1053/j.seminoncol.2020.02.010. - Tiu A, McKinnell Z, Liu S, et al. Risk of myeloproliferative neoplasms among
U.S. Veterans from Korean, Vietnam, and Persian Gulf War eras. Am J Hematol.
2024;99(10):1969-1978. doi:10.1002/ajh.27438 - Ma H, Wan JY, Cortessis VK, Gupta P, Cozen W. Survival in Agent Orange
exposed and unexposed Vietnam-era veterans who were diagnosed with
lymphoid malignancies. Blood Adv. 2024;8(4):1037-1041. doi:10.1182/
bloodadvances.2023011999 - Friedman DR, Rodgers TD, Kovalick C, Yellapragada S, Szumita L, Weiss ES. Veterans
with blood cancers: Clinical trial navigation and the challenge of rurality. J Rural
Health. 2024;40(1):114-120. doi:10.1111/jrh.12773 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(3):e100042. doi:10.1200/EDBK_100042 - Pulumati A, Pulumati A, Dwarakanath BS, Verma A, Papineni RVL. Technological
advancements in cancer diagnostics: Improvements and limitations. Cancer Rep
(Hoboken). 2023;6(2):e1764. doi:10.1002/cnr2.1764
Click to view more from Cancer Data Trends 2025.
Click to view more from Cancer Data Trends 2025.
- Li W, ed. The 5th Edition of the World Health Organization Classification of
Hematolymphoid Tumors. In: Leukemia [Internet]. Brisbane (AU): Exon Publications;
October 16, 2022. https://www.ncbi.nlm.nih.gov/books/NBK586208/ - Graf SA, Samples LS, Keating TM, Garcia JM. Clinical research in older adults with
hematologic malignancies: Opportunities for alignment in the Veterans Affairs. Semin
Oncol. 2020;47(1):94-101. doi:10.1053/j.seminoncol.2020.02.010. - Tiu A, McKinnell Z, Liu S, et al. Risk of myeloproliferative neoplasms among
U.S. Veterans from Korean, Vietnam, and Persian Gulf War eras. Am J Hematol.
2024;99(10):1969-1978. doi:10.1002/ajh.27438 - Ma H, Wan JY, Cortessis VK, Gupta P, Cozen W. Survival in Agent Orange
exposed and unexposed Vietnam-era veterans who were diagnosed with
lymphoid malignancies. Blood Adv. 2024;8(4):1037-1041. doi:10.1182/
bloodadvances.2023011999 - Friedman DR, Rodgers TD, Kovalick C, Yellapragada S, Szumita L, Weiss ES. Veterans
with blood cancers: Clinical trial navigation and the challenge of rurality. J Rural
Health. 2024;40(1):114-120. doi:10.1111/jrh.12773 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(3):e100042. doi:10.1200/EDBK_100042 - Pulumati A, Pulumati A, Dwarakanath BS, Verma A, Papineni RVL. Technological
advancements in cancer diagnostics: Improvements and limitations. Cancer Rep
(Hoboken). 2023;6(2):e1764. doi:10.1002/cnr2.1764
- Li W, ed. The 5th Edition of the World Health Organization Classification of
Hematolymphoid Tumors. In: Leukemia [Internet]. Brisbane (AU): Exon Publications;
October 16, 2022. https://www.ncbi.nlm.nih.gov/books/NBK586208/ - Graf SA, Samples LS, Keating TM, Garcia JM. Clinical research in older adults with
hematologic malignancies: Opportunities for alignment in the Veterans Affairs. Semin
Oncol. 2020;47(1):94-101. doi:10.1053/j.seminoncol.2020.02.010. - Tiu A, McKinnell Z, Liu S, et al. Risk of myeloproliferative neoplasms among
U.S. Veterans from Korean, Vietnam, and Persian Gulf War eras. Am J Hematol.
2024;99(10):1969-1978. doi:10.1002/ajh.27438 - Ma H, Wan JY, Cortessis VK, Gupta P, Cozen W. Survival in Agent Orange
exposed and unexposed Vietnam-era veterans who were diagnosed with
lymphoid malignancies. Blood Adv. 2024;8(4):1037-1041. doi:10.1182/
bloodadvances.2023011999 - Friedman DR, Rodgers TD, Kovalick C, Yellapragada S, Szumita L, Weiss ES. Veterans
with blood cancers: Clinical trial navigation and the challenge of rurality. J Rural
Health. 2024;40(1):114-120. doi:10.1111/jrh.12773 - Parikh DA, Rodgers TD, Passero VA, et al. Teleoncology in the Veterans Health
Administration: Models of Care and the Veteran Experience. Am Soc Clin Oncol Educ
Book. 2024;44(3):e100042. doi:10.1200/EDBK_100042 - Pulumati A, Pulumati A, Dwarakanath BS, Verma A, Papineni RVL. Technological
advancements in cancer diagnostics: Improvements and limitations. Cancer Rep
(Hoboken). 2023;6(2):e1764. doi:10.1002/cnr2.1764
Advances in Blood Cancer Care for Veterans
Advances in Blood Cancer Care for Veterans
Access, Race, and "Colon Age": Improving CRC Screening
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12-49. doi: 10.3322/caac.21820.
2. Riviere P, Morgan KM, Deshler LN, et al. Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis. Front Public Health. 2024;12:1414361. doi:10.3389/fpubh.2024.1414361
3. Imperiale TF, Myers LJ, Barker BC, Stump TE, Daggy JK. Colon Age: A metric for whether and how to screen male veterans for early-onset colorectal cancer. Cancer Prev Res. 2024:17:377-384. doi:10.1158/1940-6207.CAPR-23-0544
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12-49. doi: 10.3322/caac.21820.
2. Riviere P, Morgan KM, Deshler LN, et al. Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis. Front Public Health. 2024;12:1414361. doi:10.3389/fpubh.2024.1414361
3. Imperiale TF, Myers LJ, Barker BC, Stump TE, Daggy JK. Colon Age: A metric for whether and how to screen male veterans for early-onset colorectal cancer. Cancer Prev Res. 2024:17:377-384. doi:10.1158/1940-6207.CAPR-23-0544
1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74:12-49. doi: 10.3322/caac.21820.
2. Riviere P, Morgan KM, Deshler LN, et al. Racial disparities in colorectal cancer outcomes and access to care: a multi-cohort analysis. Front Public Health. 2024;12:1414361. doi:10.3389/fpubh.2024.1414361
3. Imperiale TF, Myers LJ, Barker BC, Stump TE, Daggy JK. Colon Age: A metric for whether and how to screen male veterans for early-onset colorectal cancer. Cancer Prev Res. 2024:17:377-384. doi:10.1158/1940-6207.CAPR-23-0544
HCC Updates: Quality Care Framework and Risk Stratification Data
HCC Updates: Quality Care Framework and Risk Stratification Data
Click here to view more from Cancer Data Trends 2025.
1. Rogal SS, Taddei TH, Monto A, et al. Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project. Clin Gastroenterol Hepatol. 2024 Feb;22(2):324-338. doi:10.1016/j.cgh.2023.07.002
2. John BV, Dang Y, Kaplan DE, et al. Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Apr;22(4):778-788.e7. doi:10.1016/j.cgh.2023.11.020
Click here to view more from Cancer Data Trends 2025.
Click here to view more from Cancer Data Trends 2025.
1. Rogal SS, Taddei TH, Monto A, et al. Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project. Clin Gastroenterol Hepatol. 2024 Feb;22(2):324-338. doi:10.1016/j.cgh.2023.07.002
2. John BV, Dang Y, Kaplan DE, et al. Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Apr;22(4):778-788.e7. doi:10.1016/j.cgh.2023.11.020
1. Rogal SS, Taddei TH, Monto A, et al. Hepatocellular Carcinoma Diagnosis and Management in 2021: A National Veterans Affairs Quality Improvement Project. Clin Gastroenterol Hepatol. 2024 Feb;22(2):324-338. doi:10.1016/j.cgh.2023.07.002
2. John BV, Dang Y, Kaplan DE, et al. Liver Stiffness Measurement and Risk Prediction of Hepatocellular Carcinoma After HCV Eradication in Veterans With Cirrhosis. Clin Gastroenterol Hepatol. 2024 Apr;22(4):778-788.e7. doi:10.1016/j.cgh.2023.11.020
HCC Updates: Quality Care Framework and Risk Stratification Data
HCC Updates: Quality Care Framework and Risk Stratification Data
Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
Click here to view more from Cancer Data Trends 2025.
References
Lillard JW Jr, Moses KA, Mahal BA, George DJ. Racial disparities in Black men with prostate cancer: A literature review. Cancer. 2022 Nov 1;128(21):3787-3795. doi:10.1002/cncr.34433
Wang BR, Chen Y-A, Kao W-H, Lai C-H, Lin H, Hsieh J-T. Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease. Biomedicines. 2022 Aug 3;10(8):1872. doi:10.3390/biomedicines10081872
Valle LF, Li J, Desai H, Hausler R, et al. Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing. bioRxiv [Preprint]. 2024 Oct 25:2024.10.24.620071. doi:10.1101/2024.10.24.620071
Kwon DH, Scheuner MT, McPhaul M, et al. Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits. JNCI Cancer Spectr. 2024 Sep 2;8(5):pkae079. doi:10.1093/jncics/pkae079
Kwon DH, McPhaul M, Sumra S, et al. Informed decision-making about germline testing among Veterans with advanced prostate cancer (APC): A mixed-methods study. J Clin Oncol. 2024;42(16_suppl):5105. doi:10.1200/JCO.2024.42.16_suppl.5105
Schoen MW, Montgomery RB, Owens L, Khan S, Sanfilippo KM, Etzioni RB. Survival in Patients With De Novo Metastatic Prostate Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e241970. doi: 10.1001/jamanetworkopen.2024.1970
Schafer EJ, Jemal A, Wiese D, et al. Disparities and Trends in Genitourinary Cancer Incidence and Mortality in the USA. Eur Urol. 2023 Jul;84(1):117-126. doi:10.1016/j.eururo.2022.11.023
U.S. Department of Veterans Affairs. Hines VA Hospital & Loyola University Chicago Physician Awarded $8.6M VA Research Grant. November 8, 2021. https://www.va.gov/hines-health-care/news-releases/hines-va-hospital-loyola-university-chicago-physician-awarded-86m-va-research-grant/ Accessed December 31, 2024.
U.S. Department of Veterans Affairs. National Oncology Program. How VA is Advancing Prostate Cancer Care. https://www.cancer.va.gov/prostate.html Accessed December 31, 2024.
Click here to view more from Cancer Data Trends 2025.
Click here to view more from Cancer Data Trends 2025.
References
Lillard JW Jr, Moses KA, Mahal BA, George DJ. Racial disparities in Black men with prostate cancer: A literature review. Cancer. 2022 Nov 1;128(21):3787-3795. doi:10.1002/cncr.34433
Wang BR, Chen Y-A, Kao W-H, Lai C-H, Lin H, Hsieh J-T. Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease. Biomedicines. 2022 Aug 3;10(8):1872. doi:10.3390/biomedicines10081872
Valle LF, Li J, Desai H, Hausler R, et al. Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing. bioRxiv [Preprint]. 2024 Oct 25:2024.10.24.620071. doi:10.1101/2024.10.24.620071
Kwon DH, Scheuner MT, McPhaul M, et al. Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits. JNCI Cancer Spectr. 2024 Sep 2;8(5):pkae079. doi:10.1093/jncics/pkae079
Kwon DH, McPhaul M, Sumra S, et al. Informed decision-making about germline testing among Veterans with advanced prostate cancer (APC): A mixed-methods study. J Clin Oncol. 2024;42(16_suppl):5105. doi:10.1200/JCO.2024.42.16_suppl.5105
Schoen MW, Montgomery RB, Owens L, Khan S, Sanfilippo KM, Etzioni RB. Survival in Patients With De Novo Metastatic Prostate Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e241970. doi: 10.1001/jamanetworkopen.2024.1970
Schafer EJ, Jemal A, Wiese D, et al. Disparities and Trends in Genitourinary Cancer Incidence and Mortality in the USA. Eur Urol. 2023 Jul;84(1):117-126. doi:10.1016/j.eururo.2022.11.023
U.S. Department of Veterans Affairs. Hines VA Hospital & Loyola University Chicago Physician Awarded $8.6M VA Research Grant. November 8, 2021. https://www.va.gov/hines-health-care/news-releases/hines-va-hospital-loyola-university-chicago-physician-awarded-86m-va-research-grant/ Accessed December 31, 2024.
U.S. Department of Veterans Affairs. National Oncology Program. How VA is Advancing Prostate Cancer Care. https://www.cancer.va.gov/prostate.html Accessed December 31, 2024.
References
Lillard JW Jr, Moses KA, Mahal BA, George DJ. Racial disparities in Black men with prostate cancer: A literature review. Cancer. 2022 Nov 1;128(21):3787-3795. doi:10.1002/cncr.34433
Wang BR, Chen Y-A, Kao W-H, Lai C-H, Lin H, Hsieh J-T. Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease. Biomedicines. 2022 Aug 3;10(8):1872. doi:10.3390/biomedicines10081872
Valle LF, Li J, Desai H, Hausler R, et al. Oncogenic Alterations, Race, and Survival in US Veterans with Metastatic Prostate Cancer Undergoing Somatic Tumor Next Generation Sequencing. bioRxiv [Preprint]. 2024 Oct 25:2024.10.24.620071. doi:10.1101/2024.10.24.620071
Kwon DH, Scheuner MT, McPhaul M, et al. Germline testing for veterans with advanced prostate cancer: concerns about service-connected benefits. JNCI Cancer Spectr. 2024 Sep 2;8(5):pkae079. doi:10.1093/jncics/pkae079
Kwon DH, McPhaul M, Sumra S, et al. Informed decision-making about germline testing among Veterans with advanced prostate cancer (APC): A mixed-methods study. J Clin Oncol. 2024;42(16_suppl):5105. doi:10.1200/JCO.2024.42.16_suppl.5105
Schoen MW, Montgomery RB, Owens L, Khan S, Sanfilippo KM, Etzioni RB. Survival in Patients With De Novo Metastatic Prostate Cancer. JAMA Netw Open. 2024 Mar 4;7(3):e241970. doi: 10.1001/jamanetworkopen.2024.1970
Schafer EJ, Jemal A, Wiese D, et al. Disparities and Trends in Genitourinary Cancer Incidence and Mortality in the USA. Eur Urol. 2023 Jul;84(1):117-126. doi:10.1016/j.eururo.2022.11.023
U.S. Department of Veterans Affairs. Hines VA Hospital & Loyola University Chicago Physician Awarded $8.6M VA Research Grant. November 8, 2021. https://www.va.gov/hines-health-care/news-releases/hines-va-hospital-loyola-university-chicago-physician-awarded-86m-va-research-grant/ Accessed December 31, 2024.
U.S. Department of Veterans Affairs. National Oncology Program. How VA is Advancing Prostate Cancer Care. https://www.cancer.va.gov/prostate.html Accessed December 31, 2024.
Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
Racial Disparities, Germline Testing, and Improved Overall Survival in Prostate Cancer
Lung Cancer: Mortality Trends in Veterans and New Treatments
Lung Cancer: Mortality Trends in Veterans and New Treatments
Click to view more from Cancer Data Trends 2025.
- Tehzeeb J, Mahmood F, Gemoets D, Azem A, Mehdi SA. Epidemiology and survival
trends of lung carcinoids in the veteran population. J Clin Oncol. 2023;41:e21049.
doi:10.1200/JCO.2023.41.16_suppl.e21049 - Moghanaki D, Taylor J, Bryant AK, et al. Lung Cancer Survival Trends in the Veterans
Health Administration. Clin Lung Cancer. 2024;25(3):225-232. doi:10.1016/j.
cllc.2024.02.009 - Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in
lung carcinoma from the VA National Precision Oncology Program. Semin Oncol.
2022;49(3-4):265-274. doi:10.1053/j.seminoncol.2022.06.014 - Cascone T, Awad MM, Spicer JD, et al; for the CheckMate 77T Investigators.
Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med.
2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926 - Wakelee H, Liberman M, Kato T, et al; for the KEYNOTE-671 Investigators.
Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983 - Heymach JV, Harpole D, Mitsudomi T, et al; for the AEGEAN Investigators.
Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875 - Duncan FC, Al Nasrallah N, Nephew L, et al. Racial disparities in staging, treatment,
and mortality in non-small cell lung cancer. Transl Lung Cancer Res. 2024;13(1):76-
94. doi:10.21037/tlcr-23-407
Click to view more from Cancer Data Trends 2025.
Click to view more from Cancer Data Trends 2025.
- Tehzeeb J, Mahmood F, Gemoets D, Azem A, Mehdi SA. Epidemiology and survival
trends of lung carcinoids in the veteran population. J Clin Oncol. 2023;41:e21049.
doi:10.1200/JCO.2023.41.16_suppl.e21049 - Moghanaki D, Taylor J, Bryant AK, et al. Lung Cancer Survival Trends in the Veterans
Health Administration. Clin Lung Cancer. 2024;25(3):225-232. doi:10.1016/j.
cllc.2024.02.009 - Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in
lung carcinoma from the VA National Precision Oncology Program. Semin Oncol.
2022;49(3-4):265-274. doi:10.1053/j.seminoncol.2022.06.014 - Cascone T, Awad MM, Spicer JD, et al; for the CheckMate 77T Investigators.
Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med.
2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926 - Wakelee H, Liberman M, Kato T, et al; for the KEYNOTE-671 Investigators.
Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983 - Heymach JV, Harpole D, Mitsudomi T, et al; for the AEGEAN Investigators.
Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875 - Duncan FC, Al Nasrallah N, Nephew L, et al. Racial disparities in staging, treatment,
and mortality in non-small cell lung cancer. Transl Lung Cancer Res. 2024;13(1):76-
94. doi:10.21037/tlcr-23-407
- Tehzeeb J, Mahmood F, Gemoets D, Azem A, Mehdi SA. Epidemiology and survival
trends of lung carcinoids in the veteran population. J Clin Oncol. 2023;41:e21049.
doi:10.1200/JCO.2023.41.16_suppl.e21049 - Moghanaki D, Taylor J, Bryant AK, et al. Lung Cancer Survival Trends in the Veterans
Health Administration. Clin Lung Cancer. 2024;25(3):225-232. doi:10.1016/j.
cllc.2024.02.009 - Jalal SI, Guo A, Ahmed S, Kelley MJ. Analysis of actionable genetic alterations in
lung carcinoma from the VA National Precision Oncology Program. Semin Oncol.
2022;49(3-4):265-274. doi:10.1053/j.seminoncol.2022.06.014 - Cascone T, Awad MM, Spicer JD, et al; for the CheckMate 77T Investigators.
Perioperative Nivolumab in Resectable Lung Cancer. N Engl J Med.
2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926 - Wakelee H, Liberman M, Kato T, et al; for the KEYNOTE-671 Investigators.
Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(6):491-503. doi:10.1056/NEJMoa2302983 - Heymach JV, Harpole D, Mitsudomi T, et al; for the AEGEAN Investigators.
Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer. N Engl J
Med. 2023;389(18):1672-1684. doi:10.1056/NEJMoa2304875 - Duncan FC, Al Nasrallah N, Nephew L, et al. Racial disparities in staging, treatment,
and mortality in non-small cell lung cancer. Transl Lung Cancer Res. 2024;13(1):76-
94. doi:10.21037/tlcr-23-407
Lung Cancer: Mortality Trends in Veterans and New Treatments
Lung Cancer: Mortality Trends in Veterans and New Treatments
Importance of Recognizing Hypertrophic Cardiomyopathy in the Preoperative Clinic
Importance of Recognizing Hypertrophic Cardiomyopathy in the Preoperative Clinic
Hypertrophic cardiomyopathy (HCM) is a relatively common inherited condition characterized by abnormal asymmetric left ventricular (LV) thickening. This can lead to LV outflow tract (LVOT) obstruction, which has important implications for anesthesia management. This article describes a case of previously undiagnosed HCM discovered during a preoperative physical examination prior to a routine surveillance colonoscopy.
CASE PRESENTATION
A 55-year-old Army veteran with a history of a sessile serrated colon adenoma presented to the preadmission testing clinic prior to planned surveillance colonoscopy under monitored anesthesia care. His medical history included untreated severe obstructive sleep apnea (53 apnea-hypopnea index score), diet-controlled hypertension, prediabetes (6.3% hemoglobin A1c), hypogonadism, and obesity (41 body mass index). Medications included semaglutide 1.7 mg injected subcutaneously weekly and testosterone 200 mg injected intramuscularly every 2 weeks, as well as lisinopril-hydrochlorothiazide 10 to 12.5 mg daily, which had recently been discontinued because his blood pressure had improved with a low-sodium diet.
A review of systems was unremarkable except for progressive weight gain. The patient had no family history of sudden cardiac death. On physical examination, the patient’s blood pressure was 119/81 mm Hg, pulse was 86 beats/min, and respiratory rate was 18 breaths/min. The patient was clinically euvolemic, with no jugular venous distention or peripheral edema, and his lungs were clear to auscultation. There was, however, a soft, nonradiating grade 2/6 systolic murmur that had not been previously documented. The murmur decreased substantially with the Valsalva maneuver, with no change in hand grip.
Laboratory studies revealed hemoglobin and renal function were within the reference range. A routine 12-lead electrocardiogram (ECG) was unremarkable. A transthoracic echocardiogram revealed moderate pulmonary hypertension (59 mm Hg right ventricular systolic pressure), asymmetric LV hypertrophy (2.1 cm septal thickness), and severe LVOT obstruction (131.8 mm Hg gradient). Severe systolic anterior motion of the mitral valve was also present. The LV ejection fraction was 60% to 65%, with normal cavity size and systolic function. These findings were consistent with severe hypertrophic obstructive cardiomyopathy (HOCM). Upon more detailed questioning, the patient reported that over the previous 5 years he had experienced gradually decreasing exercise tolerance and mild dyspnea on exertion, particularly in hot weather, which he attributed to weight gain. He also reported a presyncopal episode the previous month while working in his garage in hot weather for a prolonged period of time.
The patient’s elective colonoscopy was canceled, and he was referred to cardiology. While awaiting cardiac consultation, he was instructed to maintain good hydration and avoid any heavy physical activity beyond walking. He was told not to resume his use of lisinopril-hydrochlorothiazide. A screening 7-day Holter monitor showed no ventricular or supraventricular ectopy. After cardiology consultation, the patient was referred to a HCM specialty clinic, where a cardiac magnetic resonance imaging confirmed severe asymmetric hypertrophy with resting obstruction (Figures 1-4). Treatment options were discussed with the patient, and he underwent a trial with the Β—blocker metoprolol 50 mg daily, which he could not tolerate. Verapamil extended-release 180 mg orally once daily was then initiated; however, his dyspnea persisted. He was amenable to surgical therapy and underwent septal myectomy, with 12 g of septal myocardium removed. He did well postoperatively, with a follow-up echocardiogram showing normal LV systolic function and no LVOT gradient detectable at rest or with Valsalva maneuver. His fatigue and exertional dyspnea significantly improved. Once the patient underwent septal myectomy and was determined to have no detectable LVOT gradient, he was approved for colonoscopy which has been scheduled but not completed.




DISCUSSION
Once thought rare, HCM is now considered to be a relatively common inherited disorder, occurring in about 1 in 500 persons, with some suggesting that the actual prevalence is closer to 1 in 200 persons.1,2 Most often caused by mutations in ≥ 1 of 11 genes responsible for encoding cardiac sarcomere proteins, HCM is characterized by abnormal LV thickening without chamber enlargement in the absence of any identifiable cause, such as aortic valve stenosis or uncontrolled hypertension. The hypertrophy is often asymmetric, and in cases of asymmetric septal hypertrophy, dynamic LVOT obstruction can occur (known as HOCM). The condition is inherited in an autosomal dominant pattern with variable expression and is associated with myocardial fiber disarray, which can occur years before symptom onset.3 This myocardial disarray can lead to remodeling and an increased wall-to-lumen ratio of the coronary arteries, resulting in impaired coronary reserve.
Depending on the degree of LVOT obstruction, patients with HCM may be classified as nonobstructive, labile, or obstructive at rest. Patients without obstruction have an outflow gradient ≤ 30 mm Hg that is not provoked with Valsalva maneuver, administration of amyl nitrite, or exercise treadmill testing.3 Patients classified as labile do not have LVOT obstruction at rest, but obstruction may be induced by provocative measures. Finally, about one-third of patients with HCM will have LVOT gradients of > 30 mm Hg at rest. These patients are at increased risk for progression to symptomatic heart failure and may be candidates for surgical myectomy or catheter-based alcohol septal ablation.4 The patient in this case had a resting LVOT gradient of 131.8 mm Hg on echocardiography. The magnitude of this gradient placed the patient at a significantly higher risk of ventricular dysrhythmias and sudden cardiac death.5
Wall thickness also has prognostic implications. 6 Although any area of the myocardium can be affected, the septum is involved in about 90% cases. In their series of 48 patients followed over 6.5 years, Spirito et al found that the risk of sudden death in patients with HCM increased as wall thickness increased. For patients with a wall thickness of < 15 mm, the risk of death was 0 per 1000 person-years; however, this increased to 18.2 per 1000 person-years for patients with a wall thickness of > 30 mm.7
While many patients with HCM are asymptomatic, others may report dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, chest pain, palpitations, presyncope/ syncope, postural lightheadedness, fatigue, or edema. Symptomatology, however, is quite variable and does not necessarily correlate with the degree of outflow obstruction. Surprisingly, some patients with significant LVOT may have minimal symptoms, such as the patient in this case, while others with a lesser degree of LVOT obstruction may be very symptomatic.3,4
Physical examination of a patient with HCM may be normal or may reveal nonspecific findings such as a fourth heart sound or a systolic murmur. In general, physical examination abnormalities are related to LVOT obstruction. Those patients without significant outflow obstruction may have a normal cardiac examination. While patients with HCM may have a variety of systolic murmurs, the 2 most common are those related to outflow tract obstruction and mitral regurgitation caused by systolic anterior motion of the mitral valve.4 The systolic murmur associated with significant LVOT obstruction has been described as a harsh, crescendo-decrescendo type that begins just after S1 and is heard best at the apex and lower left sternal border.4 It may radiate to the axilla and base but not generally into the neck. The murmur usually increases with Valsalva maneuver and decreases with handgrip or going from a standing to a sitting/ squatting position. The initial examination of the patient in this case was not suggestive of HOCM, as confirmed by 2 practitioners (a cardiologist and an internist), each with > 30 years of clinical experience. This may have been related to the patient’s hydration status at the time, with Valsalva maneuver increasing obstruction to the point of reduced flow.
About 90% of patients with HCM will have abnormalities on ECG, most commonly LV hypertrophy with a strain pattern. Other ECG findings include: (1) prominent abnormal Q waves, particularly in the inferior (II, III, and aVF) and lateral leads (I, aVL, and V4-V6), reflecting depolarization of a hypertrophied septum; (2) left axis deviation; (3) deeply inverted T waves in leads V2 through V4; and (4) P wave abnormalities indicative of left atrial (LA) or biatrial enlargement. 8 It is notable that the patient in this case had a normal ECG, given that a minority of patients with HCM have been shown to have a normal ECG.9
Echocardiography plays an important role in diagnosing HCM. Diagnostic criteria include the presence of asymmetric hypertrophy (most commonly with anterior septal involvement), systolic anterior motion of the mitral valve, a nondilated LV cavity, septal immobility, and premature closure of the aortic valve. LV thickness is measured at both the septum and free wall; values ≥ 15 mm, with a septal-to-free wall thickness ratio of ≥ 1.3, are suggestive of HCM. Asymmetric LV hypertrophy can also be seen in other segments besides the septum, such as the apex.10
HCM/HOCM is the most common cause of sudden cardiac death in young people. The condition also contributes to significant functional morbidity due to heart failure and increases the risk of atrial fibrillation and subsequent stroke. Treatments tend to focus on symptom relief and slowing disease progression and include the use of medications such as Β—blockers, nondihydropyridine calcium channel blockers, and the myosin inhibitor mavacamten.11 Select patients, such as those with severe LVOT obstruction and symptoms despite treatment with Β—blockers or nondihydropyridine calcium channel blockers, may be offered septal myectomy or catheter-based alcohol septal ablation, coupled with insertion of an implantable cardiac defibrillator to prevent sudden cardiac death in patients at high arrhythmic risk.1,12
Patients with HCM, particularly those with LVOT obstruction, pose distinct challenges to the anesthesiologist because they are highly sensitive to decreases in preload and afterload. These patients frequently experience adverse perioperative events such as myocardial ischemia, systemic hypotension, and supraventricular or ventricular arrhythmias. Acute congestive heart failure may also occur, presumably due to concomitant diastolic dysfunction. Patients with previously unrecognized HCM are of particular concern, as they may manifest unexpected and sudden hypotension with the induction of anesthesia. There may then be a paradoxical response to vasoactive drugs and anesthetic agents, which accentuate LVOT obstruction. In these circumstances, undiagnosed HCM should be considered, and intraoperative rescue transesophageal echocardiography be performed.13 Once the diagnosis is confirmed, efforts should be made to reduce myocardial contractility and sympathetic discharge (eg, with Β—blockers), increase afterload (eg, with α1 agonists), and improve preload with adequate hydration. Proper resuscitation of hypotensive patients with HCM requires a thorough understanding of disease pathology, as effective interventions may seem to be counterintuitive. Inotropic agents such as epinephrine are contraindicated in HCM because increased inotropy and chronotropy worsen LVOT obstruction. Volume status is often tenuous; while adequate preload is important, overly aggressive fluid resuscitation may promote heart failure. It is important to keep in mind that even patients without resting LVOT obstruction may develop dynamic obstruction with anesthesia induction due to sudden reductions in preload and afterload. It is also important to note that the degree of LV hypertrophy is directly correlated with arrhythmic sudden death. Those patients with LV wall thickness ≥ 30 mm are at increased risk for potentially lethal tachyarrhythmias in the operating room.14
These considerations reinforce the need for proper preoperative identification of patients with HCM. Heightened awareness is key, given the fact that HCM is relatively common and tends to be underdiagnosed in the general population. These patients are generally young, otherwise healthy, and often undergo minor operative procedures in outpatient settings. It is incumbent upon the preoperative evaluator to take a thorough medical history and perform a careful physical examination. Clues to the diagnosis include exertional dyspnea, fatigue, angina, syncope/presyncope, or a family history of sudden cardiac death or HCM. A systolic ejection murmur, particularly one that increases with standing or Valsalva maneuver, and decreases with squatting or handgrip may also raise clinical suspicion. These patients should undergo a full cardiac evaluation, including echocardiography.
CONCLUSIONS
HCM is a common condition that is important to diagnose in the preoperative clinic. Failure to do so can lead to catastrophic complications during induction of anesthesia due to the sudden reduction in preload and afterload, which may cause a significant increase in LVOT obstruction. A high index of suspicion is essential, as clinical diagnosis can be challenging. The physical examination may be deceiving and symptoms are often subtle and nonspecific. It is imperative to alert the anesthesiologist before surgery so the complex hemodynamic management of patients with HOCM can be appropriately managed.
- Cheng Z, Fang T, Huang J, Guo Y, Alam M, Qian H. Hypertrophic cardiomyopathy: from phenotype and pathogenesis to treatment. Front Cardiovasc Med. 2021;8:722340. doi:10.3389/fcvm.2021.722340
- Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254. doi:10.1016/j.jacc.2015.01.019
- Hensley N, Dietrich J, Nyhan D, Mitter N, Yee MS, Brady M. Hypertrophic cardiomyopathy: a review. Anesth Analg. 2015;120(3):554-569. doi:10.1213/ ANE.0000000000000538
- Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2022;79(4):372–389. doi:10.1016/j.jacc.2021.12.002
- Jorda P, Garcia-Alvarez A. Hypertrophic cardiomyopathy: sudden cardiac death risk stratification in adults. Glob Cardiol Sci Pract. 2018;3(25). doi:10.21542/gcsp.2018.25
- Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis. 1985;28(1):1-83. doi:10.1016/0033-0620(85)90024-6
- Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342(24):1778–1785. doi:10.1056/ NEJM200006153422403
- Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy Lancet. 2017;389(10075):1253-1267. doi:10.1016/S0140-6736(16)31321-6
- Rowin EJ, Maron BJ, Appelbaum E, et al. Significance of false negative electrocardiograms in preparticipation screening of athletes for hypertrophic cardiomyopathy. Am J Cardiol. 2012;110(7):1027-1032. doi:10.1016/j. amjcard.2012.05.035
- Losi MA, Nistri S, Galderisi M et al. Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment. Cardiovasc Ultrasound. 2010;8(7). doi:10.1186/1476-7120-8-7
- Tian Z, Li L, Li X, et al. Effect of mavacamten on chinese patients with symptomatic obstructive hypertrophic cardiomyopathy: the EXPLORER-CN randomized clinical trial. JAMA Cardiol. 2023;8(10):957-965. doi:10.1001/ jamacardio.2023.3030
- Fang J, Liu Y, Zhu Y, et al. First-in-human transapical beating-heart septal myectomy in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2023;82(7):575-586. doi:10.1016/j.jacc.2023.05.052
- Jain P, Patel PA, Fabbro M 2nd. Hypertrophic cardiomyopathy and left ventricular outflow tract obstruction: expecting the unexpected. J Cardiothorac Vasc Anesth. 2018;32(1):467-477. doi:10.1053/j.jvca.2017.04.054
- Poliac LC, Barron ME, Maron BJ. Hypertrophic cardiomyopathy. Anesthesiology. 2006;104(1):183-192. doi:10.1097/00000542-200601000-00025
Hypertrophic cardiomyopathy (HCM) is a relatively common inherited condition characterized by abnormal asymmetric left ventricular (LV) thickening. This can lead to LV outflow tract (LVOT) obstruction, which has important implications for anesthesia management. This article describes a case of previously undiagnosed HCM discovered during a preoperative physical examination prior to a routine surveillance colonoscopy.
CASE PRESENTATION
A 55-year-old Army veteran with a history of a sessile serrated colon adenoma presented to the preadmission testing clinic prior to planned surveillance colonoscopy under monitored anesthesia care. His medical history included untreated severe obstructive sleep apnea (53 apnea-hypopnea index score), diet-controlled hypertension, prediabetes (6.3% hemoglobin A1c), hypogonadism, and obesity (41 body mass index). Medications included semaglutide 1.7 mg injected subcutaneously weekly and testosterone 200 mg injected intramuscularly every 2 weeks, as well as lisinopril-hydrochlorothiazide 10 to 12.5 mg daily, which had recently been discontinued because his blood pressure had improved with a low-sodium diet.
A review of systems was unremarkable except for progressive weight gain. The patient had no family history of sudden cardiac death. On physical examination, the patient’s blood pressure was 119/81 mm Hg, pulse was 86 beats/min, and respiratory rate was 18 breaths/min. The patient was clinically euvolemic, with no jugular venous distention or peripheral edema, and his lungs were clear to auscultation. There was, however, a soft, nonradiating grade 2/6 systolic murmur that had not been previously documented. The murmur decreased substantially with the Valsalva maneuver, with no change in hand grip.
Laboratory studies revealed hemoglobin and renal function were within the reference range. A routine 12-lead electrocardiogram (ECG) was unremarkable. A transthoracic echocardiogram revealed moderate pulmonary hypertension (59 mm Hg right ventricular systolic pressure), asymmetric LV hypertrophy (2.1 cm septal thickness), and severe LVOT obstruction (131.8 mm Hg gradient). Severe systolic anterior motion of the mitral valve was also present. The LV ejection fraction was 60% to 65%, with normal cavity size and systolic function. These findings were consistent with severe hypertrophic obstructive cardiomyopathy (HOCM). Upon more detailed questioning, the patient reported that over the previous 5 years he had experienced gradually decreasing exercise tolerance and mild dyspnea on exertion, particularly in hot weather, which he attributed to weight gain. He also reported a presyncopal episode the previous month while working in his garage in hot weather for a prolonged period of time.
The patient’s elective colonoscopy was canceled, and he was referred to cardiology. While awaiting cardiac consultation, he was instructed to maintain good hydration and avoid any heavy physical activity beyond walking. He was told not to resume his use of lisinopril-hydrochlorothiazide. A screening 7-day Holter monitor showed no ventricular or supraventricular ectopy. After cardiology consultation, the patient was referred to a HCM specialty clinic, where a cardiac magnetic resonance imaging confirmed severe asymmetric hypertrophy with resting obstruction (Figures 1-4). Treatment options were discussed with the patient, and he underwent a trial with the Β—blocker metoprolol 50 mg daily, which he could not tolerate. Verapamil extended-release 180 mg orally once daily was then initiated; however, his dyspnea persisted. He was amenable to surgical therapy and underwent septal myectomy, with 12 g of septal myocardium removed. He did well postoperatively, with a follow-up echocardiogram showing normal LV systolic function and no LVOT gradient detectable at rest or with Valsalva maneuver. His fatigue and exertional dyspnea significantly improved. Once the patient underwent septal myectomy and was determined to have no detectable LVOT gradient, he was approved for colonoscopy which has been scheduled but not completed.




DISCUSSION
Once thought rare, HCM is now considered to be a relatively common inherited disorder, occurring in about 1 in 500 persons, with some suggesting that the actual prevalence is closer to 1 in 200 persons.1,2 Most often caused by mutations in ≥ 1 of 11 genes responsible for encoding cardiac sarcomere proteins, HCM is characterized by abnormal LV thickening without chamber enlargement in the absence of any identifiable cause, such as aortic valve stenosis or uncontrolled hypertension. The hypertrophy is often asymmetric, and in cases of asymmetric septal hypertrophy, dynamic LVOT obstruction can occur (known as HOCM). The condition is inherited in an autosomal dominant pattern with variable expression and is associated with myocardial fiber disarray, which can occur years before symptom onset.3 This myocardial disarray can lead to remodeling and an increased wall-to-lumen ratio of the coronary arteries, resulting in impaired coronary reserve.
Depending on the degree of LVOT obstruction, patients with HCM may be classified as nonobstructive, labile, or obstructive at rest. Patients without obstruction have an outflow gradient ≤ 30 mm Hg that is not provoked with Valsalva maneuver, administration of amyl nitrite, or exercise treadmill testing.3 Patients classified as labile do not have LVOT obstruction at rest, but obstruction may be induced by provocative measures. Finally, about one-third of patients with HCM will have LVOT gradients of > 30 mm Hg at rest. These patients are at increased risk for progression to symptomatic heart failure and may be candidates for surgical myectomy or catheter-based alcohol septal ablation.4 The patient in this case had a resting LVOT gradient of 131.8 mm Hg on echocardiography. The magnitude of this gradient placed the patient at a significantly higher risk of ventricular dysrhythmias and sudden cardiac death.5
Wall thickness also has prognostic implications. 6 Although any area of the myocardium can be affected, the septum is involved in about 90% cases. In their series of 48 patients followed over 6.5 years, Spirito et al found that the risk of sudden death in patients with HCM increased as wall thickness increased. For patients with a wall thickness of < 15 mm, the risk of death was 0 per 1000 person-years; however, this increased to 18.2 per 1000 person-years for patients with a wall thickness of > 30 mm.7
While many patients with HCM are asymptomatic, others may report dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, chest pain, palpitations, presyncope/ syncope, postural lightheadedness, fatigue, or edema. Symptomatology, however, is quite variable and does not necessarily correlate with the degree of outflow obstruction. Surprisingly, some patients with significant LVOT may have minimal symptoms, such as the patient in this case, while others with a lesser degree of LVOT obstruction may be very symptomatic.3,4
Physical examination of a patient with HCM may be normal or may reveal nonspecific findings such as a fourth heart sound or a systolic murmur. In general, physical examination abnormalities are related to LVOT obstruction. Those patients without significant outflow obstruction may have a normal cardiac examination. While patients with HCM may have a variety of systolic murmurs, the 2 most common are those related to outflow tract obstruction and mitral regurgitation caused by systolic anterior motion of the mitral valve.4 The systolic murmur associated with significant LVOT obstruction has been described as a harsh, crescendo-decrescendo type that begins just after S1 and is heard best at the apex and lower left sternal border.4 It may radiate to the axilla and base but not generally into the neck. The murmur usually increases with Valsalva maneuver and decreases with handgrip or going from a standing to a sitting/ squatting position. The initial examination of the patient in this case was not suggestive of HOCM, as confirmed by 2 practitioners (a cardiologist and an internist), each with > 30 years of clinical experience. This may have been related to the patient’s hydration status at the time, with Valsalva maneuver increasing obstruction to the point of reduced flow.
About 90% of patients with HCM will have abnormalities on ECG, most commonly LV hypertrophy with a strain pattern. Other ECG findings include: (1) prominent abnormal Q waves, particularly in the inferior (II, III, and aVF) and lateral leads (I, aVL, and V4-V6), reflecting depolarization of a hypertrophied septum; (2) left axis deviation; (3) deeply inverted T waves in leads V2 through V4; and (4) P wave abnormalities indicative of left atrial (LA) or biatrial enlargement. 8 It is notable that the patient in this case had a normal ECG, given that a minority of patients with HCM have been shown to have a normal ECG.9
Echocardiography plays an important role in diagnosing HCM. Diagnostic criteria include the presence of asymmetric hypertrophy (most commonly with anterior septal involvement), systolic anterior motion of the mitral valve, a nondilated LV cavity, septal immobility, and premature closure of the aortic valve. LV thickness is measured at both the septum and free wall; values ≥ 15 mm, with a septal-to-free wall thickness ratio of ≥ 1.3, are suggestive of HCM. Asymmetric LV hypertrophy can also be seen in other segments besides the septum, such as the apex.10
HCM/HOCM is the most common cause of sudden cardiac death in young people. The condition also contributes to significant functional morbidity due to heart failure and increases the risk of atrial fibrillation and subsequent stroke. Treatments tend to focus on symptom relief and slowing disease progression and include the use of medications such as Β—blockers, nondihydropyridine calcium channel blockers, and the myosin inhibitor mavacamten.11 Select patients, such as those with severe LVOT obstruction and symptoms despite treatment with Β—blockers or nondihydropyridine calcium channel blockers, may be offered septal myectomy or catheter-based alcohol septal ablation, coupled with insertion of an implantable cardiac defibrillator to prevent sudden cardiac death in patients at high arrhythmic risk.1,12
Patients with HCM, particularly those with LVOT obstruction, pose distinct challenges to the anesthesiologist because they are highly sensitive to decreases in preload and afterload. These patients frequently experience adverse perioperative events such as myocardial ischemia, systemic hypotension, and supraventricular or ventricular arrhythmias. Acute congestive heart failure may also occur, presumably due to concomitant diastolic dysfunction. Patients with previously unrecognized HCM are of particular concern, as they may manifest unexpected and sudden hypotension with the induction of anesthesia. There may then be a paradoxical response to vasoactive drugs and anesthetic agents, which accentuate LVOT obstruction. In these circumstances, undiagnosed HCM should be considered, and intraoperative rescue transesophageal echocardiography be performed.13 Once the diagnosis is confirmed, efforts should be made to reduce myocardial contractility and sympathetic discharge (eg, with Β—blockers), increase afterload (eg, with α1 agonists), and improve preload with adequate hydration. Proper resuscitation of hypotensive patients with HCM requires a thorough understanding of disease pathology, as effective interventions may seem to be counterintuitive. Inotropic agents such as epinephrine are contraindicated in HCM because increased inotropy and chronotropy worsen LVOT obstruction. Volume status is often tenuous; while adequate preload is important, overly aggressive fluid resuscitation may promote heart failure. It is important to keep in mind that even patients without resting LVOT obstruction may develop dynamic obstruction with anesthesia induction due to sudden reductions in preload and afterload. It is also important to note that the degree of LV hypertrophy is directly correlated with arrhythmic sudden death. Those patients with LV wall thickness ≥ 30 mm are at increased risk for potentially lethal tachyarrhythmias in the operating room.14
These considerations reinforce the need for proper preoperative identification of patients with HCM. Heightened awareness is key, given the fact that HCM is relatively common and tends to be underdiagnosed in the general population. These patients are generally young, otherwise healthy, and often undergo minor operative procedures in outpatient settings. It is incumbent upon the preoperative evaluator to take a thorough medical history and perform a careful physical examination. Clues to the diagnosis include exertional dyspnea, fatigue, angina, syncope/presyncope, or a family history of sudden cardiac death or HCM. A systolic ejection murmur, particularly one that increases with standing or Valsalva maneuver, and decreases with squatting or handgrip may also raise clinical suspicion. These patients should undergo a full cardiac evaluation, including echocardiography.
CONCLUSIONS
HCM is a common condition that is important to diagnose in the preoperative clinic. Failure to do so can lead to catastrophic complications during induction of anesthesia due to the sudden reduction in preload and afterload, which may cause a significant increase in LVOT obstruction. A high index of suspicion is essential, as clinical diagnosis can be challenging. The physical examination may be deceiving and symptoms are often subtle and nonspecific. It is imperative to alert the anesthesiologist before surgery so the complex hemodynamic management of patients with HOCM can be appropriately managed.
Hypertrophic cardiomyopathy (HCM) is a relatively common inherited condition characterized by abnormal asymmetric left ventricular (LV) thickening. This can lead to LV outflow tract (LVOT) obstruction, which has important implications for anesthesia management. This article describes a case of previously undiagnosed HCM discovered during a preoperative physical examination prior to a routine surveillance colonoscopy.
CASE PRESENTATION
A 55-year-old Army veteran with a history of a sessile serrated colon adenoma presented to the preadmission testing clinic prior to planned surveillance colonoscopy under monitored anesthesia care. His medical history included untreated severe obstructive sleep apnea (53 apnea-hypopnea index score), diet-controlled hypertension, prediabetes (6.3% hemoglobin A1c), hypogonadism, and obesity (41 body mass index). Medications included semaglutide 1.7 mg injected subcutaneously weekly and testosterone 200 mg injected intramuscularly every 2 weeks, as well as lisinopril-hydrochlorothiazide 10 to 12.5 mg daily, which had recently been discontinued because his blood pressure had improved with a low-sodium diet.
A review of systems was unremarkable except for progressive weight gain. The patient had no family history of sudden cardiac death. On physical examination, the patient’s blood pressure was 119/81 mm Hg, pulse was 86 beats/min, and respiratory rate was 18 breaths/min. The patient was clinically euvolemic, with no jugular venous distention or peripheral edema, and his lungs were clear to auscultation. There was, however, a soft, nonradiating grade 2/6 systolic murmur that had not been previously documented. The murmur decreased substantially with the Valsalva maneuver, with no change in hand grip.
Laboratory studies revealed hemoglobin and renal function were within the reference range. A routine 12-lead electrocardiogram (ECG) was unremarkable. A transthoracic echocardiogram revealed moderate pulmonary hypertension (59 mm Hg right ventricular systolic pressure), asymmetric LV hypertrophy (2.1 cm septal thickness), and severe LVOT obstruction (131.8 mm Hg gradient). Severe systolic anterior motion of the mitral valve was also present. The LV ejection fraction was 60% to 65%, with normal cavity size and systolic function. These findings were consistent with severe hypertrophic obstructive cardiomyopathy (HOCM). Upon more detailed questioning, the patient reported that over the previous 5 years he had experienced gradually decreasing exercise tolerance and mild dyspnea on exertion, particularly in hot weather, which he attributed to weight gain. He also reported a presyncopal episode the previous month while working in his garage in hot weather for a prolonged period of time.
The patient’s elective colonoscopy was canceled, and he was referred to cardiology. While awaiting cardiac consultation, he was instructed to maintain good hydration and avoid any heavy physical activity beyond walking. He was told not to resume his use of lisinopril-hydrochlorothiazide. A screening 7-day Holter monitor showed no ventricular or supraventricular ectopy. After cardiology consultation, the patient was referred to a HCM specialty clinic, where a cardiac magnetic resonance imaging confirmed severe asymmetric hypertrophy with resting obstruction (Figures 1-4). Treatment options were discussed with the patient, and he underwent a trial with the Β—blocker metoprolol 50 mg daily, which he could not tolerate. Verapamil extended-release 180 mg orally once daily was then initiated; however, his dyspnea persisted. He was amenable to surgical therapy and underwent septal myectomy, with 12 g of septal myocardium removed. He did well postoperatively, with a follow-up echocardiogram showing normal LV systolic function and no LVOT gradient detectable at rest or with Valsalva maneuver. His fatigue and exertional dyspnea significantly improved. Once the patient underwent septal myectomy and was determined to have no detectable LVOT gradient, he was approved for colonoscopy which has been scheduled but not completed.




DISCUSSION
Once thought rare, HCM is now considered to be a relatively common inherited disorder, occurring in about 1 in 500 persons, with some suggesting that the actual prevalence is closer to 1 in 200 persons.1,2 Most often caused by mutations in ≥ 1 of 11 genes responsible for encoding cardiac sarcomere proteins, HCM is characterized by abnormal LV thickening without chamber enlargement in the absence of any identifiable cause, such as aortic valve stenosis or uncontrolled hypertension. The hypertrophy is often asymmetric, and in cases of asymmetric septal hypertrophy, dynamic LVOT obstruction can occur (known as HOCM). The condition is inherited in an autosomal dominant pattern with variable expression and is associated with myocardial fiber disarray, which can occur years before symptom onset.3 This myocardial disarray can lead to remodeling and an increased wall-to-lumen ratio of the coronary arteries, resulting in impaired coronary reserve.
Depending on the degree of LVOT obstruction, patients with HCM may be classified as nonobstructive, labile, or obstructive at rest. Patients without obstruction have an outflow gradient ≤ 30 mm Hg that is not provoked with Valsalva maneuver, administration of amyl nitrite, or exercise treadmill testing.3 Patients classified as labile do not have LVOT obstruction at rest, but obstruction may be induced by provocative measures. Finally, about one-third of patients with HCM will have LVOT gradients of > 30 mm Hg at rest. These patients are at increased risk for progression to symptomatic heart failure and may be candidates for surgical myectomy or catheter-based alcohol septal ablation.4 The patient in this case had a resting LVOT gradient of 131.8 mm Hg on echocardiography. The magnitude of this gradient placed the patient at a significantly higher risk of ventricular dysrhythmias and sudden cardiac death.5
Wall thickness also has prognostic implications. 6 Although any area of the myocardium can be affected, the septum is involved in about 90% cases. In their series of 48 patients followed over 6.5 years, Spirito et al found that the risk of sudden death in patients with HCM increased as wall thickness increased. For patients with a wall thickness of < 15 mm, the risk of death was 0 per 1000 person-years; however, this increased to 18.2 per 1000 person-years for patients with a wall thickness of > 30 mm.7
While many patients with HCM are asymptomatic, others may report dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea, chest pain, palpitations, presyncope/ syncope, postural lightheadedness, fatigue, or edema. Symptomatology, however, is quite variable and does not necessarily correlate with the degree of outflow obstruction. Surprisingly, some patients with significant LVOT may have minimal symptoms, such as the patient in this case, while others with a lesser degree of LVOT obstruction may be very symptomatic.3,4
Physical examination of a patient with HCM may be normal or may reveal nonspecific findings such as a fourth heart sound or a systolic murmur. In general, physical examination abnormalities are related to LVOT obstruction. Those patients without significant outflow obstruction may have a normal cardiac examination. While patients with HCM may have a variety of systolic murmurs, the 2 most common are those related to outflow tract obstruction and mitral regurgitation caused by systolic anterior motion of the mitral valve.4 The systolic murmur associated with significant LVOT obstruction has been described as a harsh, crescendo-decrescendo type that begins just after S1 and is heard best at the apex and lower left sternal border.4 It may radiate to the axilla and base but not generally into the neck. The murmur usually increases with Valsalva maneuver and decreases with handgrip or going from a standing to a sitting/ squatting position. The initial examination of the patient in this case was not suggestive of HOCM, as confirmed by 2 practitioners (a cardiologist and an internist), each with > 30 years of clinical experience. This may have been related to the patient’s hydration status at the time, with Valsalva maneuver increasing obstruction to the point of reduced flow.
About 90% of patients with HCM will have abnormalities on ECG, most commonly LV hypertrophy with a strain pattern. Other ECG findings include: (1) prominent abnormal Q waves, particularly in the inferior (II, III, and aVF) and lateral leads (I, aVL, and V4-V6), reflecting depolarization of a hypertrophied septum; (2) left axis deviation; (3) deeply inverted T waves in leads V2 through V4; and (4) P wave abnormalities indicative of left atrial (LA) or biatrial enlargement. 8 It is notable that the patient in this case had a normal ECG, given that a minority of patients with HCM have been shown to have a normal ECG.9
Echocardiography plays an important role in diagnosing HCM. Diagnostic criteria include the presence of asymmetric hypertrophy (most commonly with anterior septal involvement), systolic anterior motion of the mitral valve, a nondilated LV cavity, septal immobility, and premature closure of the aortic valve. LV thickness is measured at both the septum and free wall; values ≥ 15 mm, with a septal-to-free wall thickness ratio of ≥ 1.3, are suggestive of HCM. Asymmetric LV hypertrophy can also be seen in other segments besides the septum, such as the apex.10
HCM/HOCM is the most common cause of sudden cardiac death in young people. The condition also contributes to significant functional morbidity due to heart failure and increases the risk of atrial fibrillation and subsequent stroke. Treatments tend to focus on symptom relief and slowing disease progression and include the use of medications such as Β—blockers, nondihydropyridine calcium channel blockers, and the myosin inhibitor mavacamten.11 Select patients, such as those with severe LVOT obstruction and symptoms despite treatment with Β—blockers or nondihydropyridine calcium channel blockers, may be offered septal myectomy or catheter-based alcohol septal ablation, coupled with insertion of an implantable cardiac defibrillator to prevent sudden cardiac death in patients at high arrhythmic risk.1,12
Patients with HCM, particularly those with LVOT obstruction, pose distinct challenges to the anesthesiologist because they are highly sensitive to decreases in preload and afterload. These patients frequently experience adverse perioperative events such as myocardial ischemia, systemic hypotension, and supraventricular or ventricular arrhythmias. Acute congestive heart failure may also occur, presumably due to concomitant diastolic dysfunction. Patients with previously unrecognized HCM are of particular concern, as they may manifest unexpected and sudden hypotension with the induction of anesthesia. There may then be a paradoxical response to vasoactive drugs and anesthetic agents, which accentuate LVOT obstruction. In these circumstances, undiagnosed HCM should be considered, and intraoperative rescue transesophageal echocardiography be performed.13 Once the diagnosis is confirmed, efforts should be made to reduce myocardial contractility and sympathetic discharge (eg, with Β—blockers), increase afterload (eg, with α1 agonists), and improve preload with adequate hydration. Proper resuscitation of hypotensive patients with HCM requires a thorough understanding of disease pathology, as effective interventions may seem to be counterintuitive. Inotropic agents such as epinephrine are contraindicated in HCM because increased inotropy and chronotropy worsen LVOT obstruction. Volume status is often tenuous; while adequate preload is important, overly aggressive fluid resuscitation may promote heart failure. It is important to keep in mind that even patients without resting LVOT obstruction may develop dynamic obstruction with anesthesia induction due to sudden reductions in preload and afterload. It is also important to note that the degree of LV hypertrophy is directly correlated with arrhythmic sudden death. Those patients with LV wall thickness ≥ 30 mm are at increased risk for potentially lethal tachyarrhythmias in the operating room.14
These considerations reinforce the need for proper preoperative identification of patients with HCM. Heightened awareness is key, given the fact that HCM is relatively common and tends to be underdiagnosed in the general population. These patients are generally young, otherwise healthy, and often undergo minor operative procedures in outpatient settings. It is incumbent upon the preoperative evaluator to take a thorough medical history and perform a careful physical examination. Clues to the diagnosis include exertional dyspnea, fatigue, angina, syncope/presyncope, or a family history of sudden cardiac death or HCM. A systolic ejection murmur, particularly one that increases with standing or Valsalva maneuver, and decreases with squatting or handgrip may also raise clinical suspicion. These patients should undergo a full cardiac evaluation, including echocardiography.
CONCLUSIONS
HCM is a common condition that is important to diagnose in the preoperative clinic. Failure to do so can lead to catastrophic complications during induction of anesthesia due to the sudden reduction in preload and afterload, which may cause a significant increase in LVOT obstruction. A high index of suspicion is essential, as clinical diagnosis can be challenging. The physical examination may be deceiving and symptoms are often subtle and nonspecific. It is imperative to alert the anesthesiologist before surgery so the complex hemodynamic management of patients with HOCM can be appropriately managed.
- Cheng Z, Fang T, Huang J, Guo Y, Alam M, Qian H. Hypertrophic cardiomyopathy: from phenotype and pathogenesis to treatment. Front Cardiovasc Med. 2021;8:722340. doi:10.3389/fcvm.2021.722340
- Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254. doi:10.1016/j.jacc.2015.01.019
- Hensley N, Dietrich J, Nyhan D, Mitter N, Yee MS, Brady M. Hypertrophic cardiomyopathy: a review. Anesth Analg. 2015;120(3):554-569. doi:10.1213/ ANE.0000000000000538
- Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2022;79(4):372–389. doi:10.1016/j.jacc.2021.12.002
- Jorda P, Garcia-Alvarez A. Hypertrophic cardiomyopathy: sudden cardiac death risk stratification in adults. Glob Cardiol Sci Pract. 2018;3(25). doi:10.21542/gcsp.2018.25
- Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis. 1985;28(1):1-83. doi:10.1016/0033-0620(85)90024-6
- Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342(24):1778–1785. doi:10.1056/ NEJM200006153422403
- Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy Lancet. 2017;389(10075):1253-1267. doi:10.1016/S0140-6736(16)31321-6
- Rowin EJ, Maron BJ, Appelbaum E, et al. Significance of false negative electrocardiograms in preparticipation screening of athletes for hypertrophic cardiomyopathy. Am J Cardiol. 2012;110(7):1027-1032. doi:10.1016/j. amjcard.2012.05.035
- Losi MA, Nistri S, Galderisi M et al. Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment. Cardiovasc Ultrasound. 2010;8(7). doi:10.1186/1476-7120-8-7
- Tian Z, Li L, Li X, et al. Effect of mavacamten on chinese patients with symptomatic obstructive hypertrophic cardiomyopathy: the EXPLORER-CN randomized clinical trial. JAMA Cardiol. 2023;8(10):957-965. doi:10.1001/ jamacardio.2023.3030
- Fang J, Liu Y, Zhu Y, et al. First-in-human transapical beating-heart septal myectomy in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2023;82(7):575-586. doi:10.1016/j.jacc.2023.05.052
- Jain P, Patel PA, Fabbro M 2nd. Hypertrophic cardiomyopathy and left ventricular outflow tract obstruction: expecting the unexpected. J Cardiothorac Vasc Anesth. 2018;32(1):467-477. doi:10.1053/j.jvca.2017.04.054
- Poliac LC, Barron ME, Maron BJ. Hypertrophic cardiomyopathy. Anesthesiology. 2006;104(1):183-192. doi:10.1097/00000542-200601000-00025
- Cheng Z, Fang T, Huang J, Guo Y, Alam M, Qian H. Hypertrophic cardiomyopathy: from phenotype and pathogenesis to treatment. Front Cardiovasc Med. 2021;8:722340. doi:10.3389/fcvm.2021.722340
- Semsarian C, Ingles J, Maron MS, Maron BJ. New perspectives on the prevalence of hypertrophic cardiomyopathy. J Am Coll Cardiol. 2015;65(12):1249-1254. doi:10.1016/j.jacc.2015.01.019
- Hensley N, Dietrich J, Nyhan D, Mitter N, Yee MS, Brady M. Hypertrophic cardiomyopathy: a review. Anesth Analg. 2015;120(3):554-569. doi:10.1213/ ANE.0000000000000538
- Maron BJ, Desai MY, Nishimura RA, et al. Diagnosis and evaluation of hypertrophic cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2022;79(4):372–389. doi:10.1016/j.jacc.2021.12.002
- Jorda P, Garcia-Alvarez A. Hypertrophic cardiomyopathy: sudden cardiac death risk stratification in adults. Glob Cardiol Sci Pract. 2018;3(25). doi:10.21542/gcsp.2018.25
- Wigle ED, Sasson Z, Henderson MA, et al. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Cardiovasc Dis. 1985;28(1):1-83. doi:10.1016/0033-0620(85)90024-6
- Spirito P, Bellone P, Harris KM, Bernabo P, Bruzzi P, Maron BJ. Magnitude of left ventricular hypertrophy and risk of sudden death in hypertrophic cardiomyopathy. N Engl J Med. 2000;342(24):1778–1785. doi:10.1056/ NEJM200006153422403
- Veselka J, Anavekar NS, Charron P. Hypertrophic obstructive cardiomyopathy Lancet. 2017;389(10075):1253-1267. doi:10.1016/S0140-6736(16)31321-6
- Rowin EJ, Maron BJ, Appelbaum E, et al. Significance of false negative electrocardiograms in preparticipation screening of athletes for hypertrophic cardiomyopathy. Am J Cardiol. 2012;110(7):1027-1032. doi:10.1016/j. amjcard.2012.05.035
- Losi MA, Nistri S, Galderisi M et al. Echocardiography in patients with hypertrophic cardiomyopathy: usefulness of old and new techniques in the diagnosis and pathophysiological assessment. Cardiovasc Ultrasound. 2010;8(7). doi:10.1186/1476-7120-8-7
- Tian Z, Li L, Li X, et al. Effect of mavacamten on chinese patients with symptomatic obstructive hypertrophic cardiomyopathy: the EXPLORER-CN randomized clinical trial. JAMA Cardiol. 2023;8(10):957-965. doi:10.1001/ jamacardio.2023.3030
- Fang J, Liu Y, Zhu Y, et al. First-in-human transapical beating-heart septal myectomy in patients with hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2023;82(7):575-586. doi:10.1016/j.jacc.2023.05.052
- Jain P, Patel PA, Fabbro M 2nd. Hypertrophic cardiomyopathy and left ventricular outflow tract obstruction: expecting the unexpected. J Cardiothorac Vasc Anesth. 2018;32(1):467-477. doi:10.1053/j.jvca.2017.04.054
- Poliac LC, Barron ME, Maron BJ. Hypertrophic cardiomyopathy. Anesthesiology. 2006;104(1):183-192. doi:10.1097/00000542-200601000-00025
Importance of Recognizing Hypertrophic Cardiomyopathy in the Preoperative Clinic
Importance of Recognizing Hypertrophic Cardiomyopathy in the Preoperative Clinic
Statin-Induced Necrotizing Autoimmune Myopathy in a Patient With Complex Diabetes Management
Statin-Induced Necrotizing Autoimmune Myopathy in a Patient With Complex Diabetes Management
Muscle-related complaints occur in 7% to 25% of patients taking statin medications.1 In most instances, these adverse effects are quickly resolved when the medication is discontinued, but in rare occurrences, the statin can trigger an autoimmune response that progresses even after stopping use. This uncommon condition is typically accompanied by symmetrical proximal muscle weakness and an elevated CPK leading to a necrotizing myopathy requiring treatment with immunosuppressive therapy. Although less common, some patients may also present with dysphagia, myalgia, weight loss, and/or skin rash.1
Statin medications have been the cornerstone of lipid-lowering therapy due to their mechanism of inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is the rate-limiting step within the cholesterol synthesis pathway to produce mevalonic acid. There is a proven genetic association with human leukocyte antigen (HLA)-DRB1*11:01 in adults and anti-HMGCR–associated myopathy.1 The incidence of statin-induced necrotizing autoimmune myopathy (SINAM) in relation to each specific statin agent remains unknown; however, a systematic review of case reports found higher correlations for atorvastatin and simvastatin.2
There are 2 ways to confirm a SINAM diagnosis. The first and simplest includes checking for the presence of antibodies against HMGCR. The anti-HMGCR antibody test is typically used as a definitive diagnosis because it has a high specificity for SINAM.3 The second and more invasive diagnosis method involves a muscle biopsy, which is identified as positive if the biopsy shows the presence of necrotic muscle fibers.1,3
The anti-HMGCR antibody test can serve as a marker for disease activity because the antibodies are strongly correlated with CPK levels.1 CPK levels indicate the severity of muscle injury and is often used in addition to either of the confirmatory tests because it is faster and less expensive. Anti-HMGCR titers may remain positive while CPK returns to baseline when SINAM is dormant. In addition, clinicians may use an electromyography (EMG) test to measure the muscle response in association to nerve stimulation. 1 This test can show potential features of myopathic lesions such as positive sharp waves, spontaneous fibrillations, or myotonic repetitive potentials.
Typical treatment includes glucocorticoids as first-line agents, but SINAM can be difficult to treat due to its complicated pathophysiology processes.3 Escalation of therapy is sometimes required beyond a single agent; in these complex scenarios, methotrexate and/or intravenous (IV) immunoglobulin (IVIG) therapy are frequently added to the steroid therapy. There have been concerns with steroid use in specific patient populations due to the undesired adverse effect (AE) profile, and as a result IVIG has been used as monotherapy at a dose of 2 g/kg per month.3 Studies looking at IVIG monotherapy showed a reduction in CPK levels and improvement in strength after just 2 to 3 rounds of monthly treatment.3 Some patients receiving IVIG monotherapy even achieved baseline strength and no longer reported muscle-related symptoms, although the total treatment duration varied. A systematic review of 39 articles where glucocorticoids, IVIG, methotrexate and/or a combination were used to treat SINAM found an average time to remission of 8.6 months. Additionally, this systematic review observed more patients returned to baseline or experienced improvement in symptoms when being treated with a combination of glucocorticoid plus IVIG plus methotrexate.2 Suggested dosing recommendations are available in Table 1.

Patients diagnosed with HMGCR antibody myopathy are contraindicated for future statin therapy.1 Rechallenge of statins in this patient population has led to worsening of disease and therefore these patients should have a severe statin allergy listed in their medical documentation record.
CASE PRESENTATION
A 59-year-old male patient with a medical history including atrial fibrillation, peripheral vascular disease, type 2 diabetes mellitus (T2DM), hypertension, and peripheral neuropathy was referred by his primary care clinical pharmacist practitioner for an outpatient neurology consult. The patient reported a 4-month history of fatigue, lower extremity paresthesia, and progressive proximal muscle weakness which began in his legs, mostly noticeable when walking upstairs but quickly developed into bilateral arm weakness. The patient reported significant impact on his quality of life: he could no longer lift his arms above his head and had difficulty with daily activities such as brushing his hair or getting up from a chair. He reported multiple falls at home, and began to use a cane for assistance with ambulation. He confirmed adherence to atorvastatin over the past year. Laboratory testing on the day of the visit revealed an elevated CPK level at 9729 mcg/L (reference range for men, 30-300 mcg/L).
The patient was urged to go to the emergency department where his CPK level had increased to 12,990 mcg/L (Figure 1). The workup began to find the source of rhabdomyolysis and elevated liver enzymes differentiating autoimmune vs medication-induced myopathy. Upon admission atorvastatin was discontinued, anti-HMGCR antibody level was ordered, and IV fluids were started.

After 8 days of hospital admission with minimal improvement, Rheumatology and Neurology services were consulted in the setting of persistent CPK elevation and the potential neuropathic component of muscle weakness. Both consulting services agreed to consider muscle biopsy and EMG if the patient did not begin to show signs of improvement. The patient’s CPK levels remained elevated with minimal change in muscle weakness. The next step was a right quadricep muscle biopsy performed on Day 14 of admission. Sixteen days after admission, the anti-HMGCR antibody test (originally obtained upon admission) was positive and elevated at 249 CU/mL (reference range, < 20 CU/mL negative; reference range, ≥ 60 CU/mL strong positive), which confirmed the SINAM diagnosis (Table 2).

On Day 17 of hospitalization, the Neurology service initiated IVIG monotherapy to avoid the undesired glycemic AEs associated with glucocorticoids. The patient had a history of T2DM that was difficult to manage and his hemoglobin A1c level was the best it had ever been (6.2%) relative to a peak A1c of 11.0% 9 months prior. The patient was treated with a total IVIG dose of 2 g/kg divided into 3 daily doses while still obtaining CPK levels with daily laboratory tests to assist with trending the extent of disease severity improvement (Figures 2-4). After a 20-day hospital stay, the patient was discharged home with rehabilitation services and a scheduled outpatient EMG the following week.



The patient continued to report generalized body weakness, pain, and deconditioning upon discharge and was unable to attend the EMG neurology appointment. The patient did eventually attend a follow-up appointment about 6 weeks after hospital discharge and reported continued weakness. The Neurology service prescribed a 2-day IVIG regimen (total dose = 2 g/kg) monthly for the next 2 months. The patient returned to the neurology clinic 8 weeks later following 2 rounds of IVIG posthospitalization and reported that his muscle strength was returning, and he was able to slowly reintroduce exercise into his daily routine. During a follow-up appointment about 11 months after the initial hospitalization, the patient’s primary care clinical pharmacist provided education of effective management of cholesterol without statins, including use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as recommended by the Neurology service. At this time, the patient’s calculated low-density lipoprotein (LDL) was 110 mg/dL (reference range, 0-99 mg/dL). The patient preferred to work on a healthy diet and positive lifestyle choices before trialing any lipid lowering therapies.
The patient appeared to tolerate this treatment regimen following 7 rounds of IVIG. He noted fatigue for about 24 hours after his infusion sessions but otherwise reported no additional AEs. He has continued to attend weekly physical therapy sessions and is able to walk without the assistance of a cane. He can now walk a mile before he begins to feel fatigued or experience bilateral lower leg pain. The pain appears neuropathic in nature, as the patient reports ongoing “pins and needles” sensation in his legs and feet. The patient has noticed a major improvement in his overall function, strength, and exercise tolerance since starting IVIG treatments and although he is not yet back to his baseline, he is motivated to continue his recovery. Neurology is considering ongoing treatment with IVIG monthly infusions given his continued clinical improvement.
DISCUSSION
There is limited evidence on the use of IVIG monotherapy for SINAM, although it may be a viable option for patients deemed poor candidates for glucocorticoid or methotrexate therapy. This particularly applies to patients with DM for which there may be concerns for managing blood glucose levels with steroid use. The Johns Hopkins Myositis Center evaluated 3 patients with SINAM who declined glucocorticoid therapy and had documented DM and weakness in the proximal arms and legs. Following 2 to 3 monthly rounds of IVIG 2 g/kg monotherapy, these patients had reduced CPK levels and had improvement in both arm and hip-flexion strength. Two patients reported no muscle-related symptoms after completing IVIG monotherapy treatment for 9 and 19 months.3
The optimal treatment duration for IVIG monotherapy for SINAM is still uncertain given the limited available data. The patient in this case report showed clinically significant muscle-related improvement following 7 monthly rounds of 2 g/kg IVIG treatments. The mechanism of action for IVIG in this setting is still unknown, although the medication may allow muscle regeneration to surpass muscle destruction, thus leading to resolution of the muscle-related symptoms.3
There are numerous concerns with IVIG use to consider prior to initiating treatment, including expense, AEs, patient response, and comorbidities. IVIG is considerably more expensive than glucocorticoid and methotrexate alternatives. Systemic reactions have been shown to occur in 5% to 15% of patients receiving IVIG infusion.4 The majority of these infusion reactions occur early during infusion or within a few hours after administration is complete.5 Early AEs to monitor for include injection site reactions, flu-like symptoms, dermatologic reactions, anaphylaxis, transfusion-related acute lung injury, and transfusion-associated circulatory overload. Additional AEs may be delayed, including thromboembolic events, acute kidney injury, aseptic meningitis, hemolysis, neutropenia, and blood-borne infection.6 IVIG has a boxed warning for thrombosis, renal dysfunction, and acute renal failure risk.7 There are multiple strategies documented to reduce the risk of IVIG reactions including slowing the infusion rate, ensuring adequate hydration, and/or giving analgesics, antihistamines, or steroids prior to infusion.6 The patient in this case had monthly IVIG infusions without the need of any pretreatment medications and only reported fatigue for about 24 hours following the infusion.
An essential question is how to provide safe cholesterol management for patients with SINAM. Some evidence has suggested that other lipid-lowering medications that avoid the mevalonate pathway, such as fenofibrate or ezetimibe, may be used cautiously initially at lower doses.1 Due to the severity of SINAM, it is crucial to closely monitor and ensure tolerability as new lipid-lowering agents are introduced. More evidence suggests that PCSK9 inhibitors are a safer option.8 PCSK9 inhibitors avoid the mevalonate pathway and block PCSK9 from binding to LDL receptors, allowing LDL to be removed from circulation.
Tiniakou et al followed 8 individuals for a mean 1.5 years who had anti-HMGCR immune-mediated myopathy at high cardiovascular risk. Muscle strength, CPK levels, and serum anti-HMGCR antibody titers were assessed at baseline and again after initiation of PCSK9 inhibitor. None of the patients experienced a decline in their muscle strength. CPK, anti-HMGCR antibody levels, and LDL trended down in all participants and 2 patients were able to reduce their immunosuppression treatment while still achieving clinical improvement. Tiniakou et al suggest that PCSK9 inhibitors are a safe and effective option to lower cholesterol in patients with SINAM.8
Alirocumab is the preferred PCSK9 inhibitor for patients at the US Department of Veterans Affairs (VA). The VA Pharmacy Benefits Management (PBM) Service guidance recommends alirocumab for patients with a history of atherosclerotic cardiovascular disease (ASCVD) or severe hypercholesterolemia.9 PBM guidance suggests alirocumab use for patients with a contraindication, intolerance, or insufficient LDL reduction with a maximally tolerated dose of statin and ezetimibe with a desire to reduce ASCVD risk by lowering LDL. Per the PBM Criteria for Use guidance, patients should follow the stepwise approach and trial ezetimibe prior to being considered for PCSK9 inhibitor therapy. Given the patient’s contraindication to future statin use and severity of myopathy, in this case the Neurology Service felt that the safest option to reach goal LDL reduction would be a PCSK9 inhibitor. Consideration can be made for alirocumab use when considering an alternative lipid lowering therapy.
CONCLUSIONS
This report demonstrates a case of SINAM caused by atorvastatin therapy. Patients presenting with proximal muscle weakness and elevated CPK even after statin discontinuation should be considered for a full workup to determine whether SINAM may be involved. This uncommon form of myopathy can be diagnosed based on the detection of anti-HMGCR antibodies and/or presence of necrosis on muscle biopsy. A combination of glucocorticoid, methotrexate, and IVIG is recommended for a patient’s best chance of muscle symptom improvement. IVIG monotherapy should be considered for patients with glycemic control concerns.
- Tiniakou E. Statin-associated autoimmune myopathy: current perspectives. Ther Clin Risk Manag. 2020;16:483-492. doi:10.2147/TCRM.S197941
- Somagutta MKR, Shama N, Pormento MKL, et al. Statin-induced necrotizing autoimmune myopathy: a systematic review. Reumatologia. 2022;60(1):63-69. doi:10.5114/reum.2022.114108
- Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med. 2015;373(17):1680-1682. doi:10.1056/NEJMc1506163
- Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171-178. doi:10.1016/j.tmrv.2013.05.004
- Ameratunga R, Sinclair J, Kolbe J. Increased risk of adverse events when changing intravenous immunoglobulin preparations. Clin Exp Immunol. 2004;136(1):111-113. doi:10.1111/j.1365-2249.2004.02412.x
- Abbas A, Rajabally YA. Complications of immunoglobulin therapy and implications for treatment of inflammatory neuropathy: a review. Curr Drug Saf. 2019;14(1):3-13. doi:10.2174/1574886313666181017121139
- Privigen. Prescribing information. CSL Behring LLC; 2022. Accessed March 17, 2025. https://labeling.cslbehring.com/PI/US/Privigen/EN/Privigen-Prescribing-Information.pdf
- Tiniakou E, Rivera E, Mammen AL, Christopher-Stine L. Use of proprotein convertase subtilisin/Kexin Type 9 inhibitors in statin-associated immune-mediated necrotizing myopathy: a case series. Arthritis Rheumatol. 2019;71(10):1723-1726. doi:10.1002/art.40919
- US Department of Veterans Affairs, Pharmacy Benefits Management (PBM) Services. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitor) (Alirocumabpreferred, Evolocumab-non-preferred) Criteria for Use. June 2024. Accessed March 25, 2025. https://www.va.gov/formularyadvisor/DOC/128
- Jayatilaka S, Desai K, Rijal S, Zimmerman D. Statin-induced autoimmune necrotizing myopathy. J Prim Care Community Health. 2021;12:21501327211028714. doi:10.1177/21501327211028714
Muscle-related complaints occur in 7% to 25% of patients taking statin medications.1 In most instances, these adverse effects are quickly resolved when the medication is discontinued, but in rare occurrences, the statin can trigger an autoimmune response that progresses even after stopping use. This uncommon condition is typically accompanied by symmetrical proximal muscle weakness and an elevated CPK leading to a necrotizing myopathy requiring treatment with immunosuppressive therapy. Although less common, some patients may also present with dysphagia, myalgia, weight loss, and/or skin rash.1
Statin medications have been the cornerstone of lipid-lowering therapy due to their mechanism of inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is the rate-limiting step within the cholesterol synthesis pathway to produce mevalonic acid. There is a proven genetic association with human leukocyte antigen (HLA)-DRB1*11:01 in adults and anti-HMGCR–associated myopathy.1 The incidence of statin-induced necrotizing autoimmune myopathy (SINAM) in relation to each specific statin agent remains unknown; however, a systematic review of case reports found higher correlations for atorvastatin and simvastatin.2
There are 2 ways to confirm a SINAM diagnosis. The first and simplest includes checking for the presence of antibodies against HMGCR. The anti-HMGCR antibody test is typically used as a definitive diagnosis because it has a high specificity for SINAM.3 The second and more invasive diagnosis method involves a muscle biopsy, which is identified as positive if the biopsy shows the presence of necrotic muscle fibers.1,3
The anti-HMGCR antibody test can serve as a marker for disease activity because the antibodies are strongly correlated with CPK levels.1 CPK levels indicate the severity of muscle injury and is often used in addition to either of the confirmatory tests because it is faster and less expensive. Anti-HMGCR titers may remain positive while CPK returns to baseline when SINAM is dormant. In addition, clinicians may use an electromyography (EMG) test to measure the muscle response in association to nerve stimulation. 1 This test can show potential features of myopathic lesions such as positive sharp waves, spontaneous fibrillations, or myotonic repetitive potentials.
Typical treatment includes glucocorticoids as first-line agents, but SINAM can be difficult to treat due to its complicated pathophysiology processes.3 Escalation of therapy is sometimes required beyond a single agent; in these complex scenarios, methotrexate and/or intravenous (IV) immunoglobulin (IVIG) therapy are frequently added to the steroid therapy. There have been concerns with steroid use in specific patient populations due to the undesired adverse effect (AE) profile, and as a result IVIG has been used as monotherapy at a dose of 2 g/kg per month.3 Studies looking at IVIG monotherapy showed a reduction in CPK levels and improvement in strength after just 2 to 3 rounds of monthly treatment.3 Some patients receiving IVIG monotherapy even achieved baseline strength and no longer reported muscle-related symptoms, although the total treatment duration varied. A systematic review of 39 articles where glucocorticoids, IVIG, methotrexate and/or a combination were used to treat SINAM found an average time to remission of 8.6 months. Additionally, this systematic review observed more patients returned to baseline or experienced improvement in symptoms when being treated with a combination of glucocorticoid plus IVIG plus methotrexate.2 Suggested dosing recommendations are available in Table 1.

Patients diagnosed with HMGCR antibody myopathy are contraindicated for future statin therapy.1 Rechallenge of statins in this patient population has led to worsening of disease and therefore these patients should have a severe statin allergy listed in their medical documentation record.
CASE PRESENTATION
A 59-year-old male patient with a medical history including atrial fibrillation, peripheral vascular disease, type 2 diabetes mellitus (T2DM), hypertension, and peripheral neuropathy was referred by his primary care clinical pharmacist practitioner for an outpatient neurology consult. The patient reported a 4-month history of fatigue, lower extremity paresthesia, and progressive proximal muscle weakness which began in his legs, mostly noticeable when walking upstairs but quickly developed into bilateral arm weakness. The patient reported significant impact on his quality of life: he could no longer lift his arms above his head and had difficulty with daily activities such as brushing his hair or getting up from a chair. He reported multiple falls at home, and began to use a cane for assistance with ambulation. He confirmed adherence to atorvastatin over the past year. Laboratory testing on the day of the visit revealed an elevated CPK level at 9729 mcg/L (reference range for men, 30-300 mcg/L).
The patient was urged to go to the emergency department where his CPK level had increased to 12,990 mcg/L (Figure 1). The workup began to find the source of rhabdomyolysis and elevated liver enzymes differentiating autoimmune vs medication-induced myopathy. Upon admission atorvastatin was discontinued, anti-HMGCR antibody level was ordered, and IV fluids were started.

After 8 days of hospital admission with minimal improvement, Rheumatology and Neurology services were consulted in the setting of persistent CPK elevation and the potential neuropathic component of muscle weakness. Both consulting services agreed to consider muscle biopsy and EMG if the patient did not begin to show signs of improvement. The patient’s CPK levels remained elevated with minimal change in muscle weakness. The next step was a right quadricep muscle biopsy performed on Day 14 of admission. Sixteen days after admission, the anti-HMGCR antibody test (originally obtained upon admission) was positive and elevated at 249 CU/mL (reference range, < 20 CU/mL negative; reference range, ≥ 60 CU/mL strong positive), which confirmed the SINAM diagnosis (Table 2).

On Day 17 of hospitalization, the Neurology service initiated IVIG monotherapy to avoid the undesired glycemic AEs associated with glucocorticoids. The patient had a history of T2DM that was difficult to manage and his hemoglobin A1c level was the best it had ever been (6.2%) relative to a peak A1c of 11.0% 9 months prior. The patient was treated with a total IVIG dose of 2 g/kg divided into 3 daily doses while still obtaining CPK levels with daily laboratory tests to assist with trending the extent of disease severity improvement (Figures 2-4). After a 20-day hospital stay, the patient was discharged home with rehabilitation services and a scheduled outpatient EMG the following week.



The patient continued to report generalized body weakness, pain, and deconditioning upon discharge and was unable to attend the EMG neurology appointment. The patient did eventually attend a follow-up appointment about 6 weeks after hospital discharge and reported continued weakness. The Neurology service prescribed a 2-day IVIG regimen (total dose = 2 g/kg) monthly for the next 2 months. The patient returned to the neurology clinic 8 weeks later following 2 rounds of IVIG posthospitalization and reported that his muscle strength was returning, and he was able to slowly reintroduce exercise into his daily routine. During a follow-up appointment about 11 months after the initial hospitalization, the patient’s primary care clinical pharmacist provided education of effective management of cholesterol without statins, including use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as recommended by the Neurology service. At this time, the patient’s calculated low-density lipoprotein (LDL) was 110 mg/dL (reference range, 0-99 mg/dL). The patient preferred to work on a healthy diet and positive lifestyle choices before trialing any lipid lowering therapies.
The patient appeared to tolerate this treatment regimen following 7 rounds of IVIG. He noted fatigue for about 24 hours after his infusion sessions but otherwise reported no additional AEs. He has continued to attend weekly physical therapy sessions and is able to walk without the assistance of a cane. He can now walk a mile before he begins to feel fatigued or experience bilateral lower leg pain. The pain appears neuropathic in nature, as the patient reports ongoing “pins and needles” sensation in his legs and feet. The patient has noticed a major improvement in his overall function, strength, and exercise tolerance since starting IVIG treatments and although he is not yet back to his baseline, he is motivated to continue his recovery. Neurology is considering ongoing treatment with IVIG monthly infusions given his continued clinical improvement.
DISCUSSION
There is limited evidence on the use of IVIG monotherapy for SINAM, although it may be a viable option for patients deemed poor candidates for glucocorticoid or methotrexate therapy. This particularly applies to patients with DM for which there may be concerns for managing blood glucose levels with steroid use. The Johns Hopkins Myositis Center evaluated 3 patients with SINAM who declined glucocorticoid therapy and had documented DM and weakness in the proximal arms and legs. Following 2 to 3 monthly rounds of IVIG 2 g/kg monotherapy, these patients had reduced CPK levels and had improvement in both arm and hip-flexion strength. Two patients reported no muscle-related symptoms after completing IVIG monotherapy treatment for 9 and 19 months.3
The optimal treatment duration for IVIG monotherapy for SINAM is still uncertain given the limited available data. The patient in this case report showed clinically significant muscle-related improvement following 7 monthly rounds of 2 g/kg IVIG treatments. The mechanism of action for IVIG in this setting is still unknown, although the medication may allow muscle regeneration to surpass muscle destruction, thus leading to resolution of the muscle-related symptoms.3
There are numerous concerns with IVIG use to consider prior to initiating treatment, including expense, AEs, patient response, and comorbidities. IVIG is considerably more expensive than glucocorticoid and methotrexate alternatives. Systemic reactions have been shown to occur in 5% to 15% of patients receiving IVIG infusion.4 The majority of these infusion reactions occur early during infusion or within a few hours after administration is complete.5 Early AEs to monitor for include injection site reactions, flu-like symptoms, dermatologic reactions, anaphylaxis, transfusion-related acute lung injury, and transfusion-associated circulatory overload. Additional AEs may be delayed, including thromboembolic events, acute kidney injury, aseptic meningitis, hemolysis, neutropenia, and blood-borne infection.6 IVIG has a boxed warning for thrombosis, renal dysfunction, and acute renal failure risk.7 There are multiple strategies documented to reduce the risk of IVIG reactions including slowing the infusion rate, ensuring adequate hydration, and/or giving analgesics, antihistamines, or steroids prior to infusion.6 The patient in this case had monthly IVIG infusions without the need of any pretreatment medications and only reported fatigue for about 24 hours following the infusion.
An essential question is how to provide safe cholesterol management for patients with SINAM. Some evidence has suggested that other lipid-lowering medications that avoid the mevalonate pathway, such as fenofibrate or ezetimibe, may be used cautiously initially at lower doses.1 Due to the severity of SINAM, it is crucial to closely monitor and ensure tolerability as new lipid-lowering agents are introduced. More evidence suggests that PCSK9 inhibitors are a safer option.8 PCSK9 inhibitors avoid the mevalonate pathway and block PCSK9 from binding to LDL receptors, allowing LDL to be removed from circulation.
Tiniakou et al followed 8 individuals for a mean 1.5 years who had anti-HMGCR immune-mediated myopathy at high cardiovascular risk. Muscle strength, CPK levels, and serum anti-HMGCR antibody titers were assessed at baseline and again after initiation of PCSK9 inhibitor. None of the patients experienced a decline in their muscle strength. CPK, anti-HMGCR antibody levels, and LDL trended down in all participants and 2 patients were able to reduce their immunosuppression treatment while still achieving clinical improvement. Tiniakou et al suggest that PCSK9 inhibitors are a safe and effective option to lower cholesterol in patients with SINAM.8
Alirocumab is the preferred PCSK9 inhibitor for patients at the US Department of Veterans Affairs (VA). The VA Pharmacy Benefits Management (PBM) Service guidance recommends alirocumab for patients with a history of atherosclerotic cardiovascular disease (ASCVD) or severe hypercholesterolemia.9 PBM guidance suggests alirocumab use for patients with a contraindication, intolerance, or insufficient LDL reduction with a maximally tolerated dose of statin and ezetimibe with a desire to reduce ASCVD risk by lowering LDL. Per the PBM Criteria for Use guidance, patients should follow the stepwise approach and trial ezetimibe prior to being considered for PCSK9 inhibitor therapy. Given the patient’s contraindication to future statin use and severity of myopathy, in this case the Neurology Service felt that the safest option to reach goal LDL reduction would be a PCSK9 inhibitor. Consideration can be made for alirocumab use when considering an alternative lipid lowering therapy.
CONCLUSIONS
This report demonstrates a case of SINAM caused by atorvastatin therapy. Patients presenting with proximal muscle weakness and elevated CPK even after statin discontinuation should be considered for a full workup to determine whether SINAM may be involved. This uncommon form of myopathy can be diagnosed based on the detection of anti-HMGCR antibodies and/or presence of necrosis on muscle biopsy. A combination of glucocorticoid, methotrexate, and IVIG is recommended for a patient’s best chance of muscle symptom improvement. IVIG monotherapy should be considered for patients with glycemic control concerns.
Muscle-related complaints occur in 7% to 25% of patients taking statin medications.1 In most instances, these adverse effects are quickly resolved when the medication is discontinued, but in rare occurrences, the statin can trigger an autoimmune response that progresses even after stopping use. This uncommon condition is typically accompanied by symmetrical proximal muscle weakness and an elevated CPK leading to a necrotizing myopathy requiring treatment with immunosuppressive therapy. Although less common, some patients may also present with dysphagia, myalgia, weight loss, and/or skin rash.1
Statin medications have been the cornerstone of lipid-lowering therapy due to their mechanism of inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), which is the rate-limiting step within the cholesterol synthesis pathway to produce mevalonic acid. There is a proven genetic association with human leukocyte antigen (HLA)-DRB1*11:01 in adults and anti-HMGCR–associated myopathy.1 The incidence of statin-induced necrotizing autoimmune myopathy (SINAM) in relation to each specific statin agent remains unknown; however, a systematic review of case reports found higher correlations for atorvastatin and simvastatin.2
There are 2 ways to confirm a SINAM diagnosis. The first and simplest includes checking for the presence of antibodies against HMGCR. The anti-HMGCR antibody test is typically used as a definitive diagnosis because it has a high specificity for SINAM.3 The second and more invasive diagnosis method involves a muscle biopsy, which is identified as positive if the biopsy shows the presence of necrotic muscle fibers.1,3
The anti-HMGCR antibody test can serve as a marker for disease activity because the antibodies are strongly correlated with CPK levels.1 CPK levels indicate the severity of muscle injury and is often used in addition to either of the confirmatory tests because it is faster and less expensive. Anti-HMGCR titers may remain positive while CPK returns to baseline when SINAM is dormant. In addition, clinicians may use an electromyography (EMG) test to measure the muscle response in association to nerve stimulation. 1 This test can show potential features of myopathic lesions such as positive sharp waves, spontaneous fibrillations, or myotonic repetitive potentials.
Typical treatment includes glucocorticoids as first-line agents, but SINAM can be difficult to treat due to its complicated pathophysiology processes.3 Escalation of therapy is sometimes required beyond a single agent; in these complex scenarios, methotrexate and/or intravenous (IV) immunoglobulin (IVIG) therapy are frequently added to the steroid therapy. There have been concerns with steroid use in specific patient populations due to the undesired adverse effect (AE) profile, and as a result IVIG has been used as monotherapy at a dose of 2 g/kg per month.3 Studies looking at IVIG monotherapy showed a reduction in CPK levels and improvement in strength after just 2 to 3 rounds of monthly treatment.3 Some patients receiving IVIG monotherapy even achieved baseline strength and no longer reported muscle-related symptoms, although the total treatment duration varied. A systematic review of 39 articles where glucocorticoids, IVIG, methotrexate and/or a combination were used to treat SINAM found an average time to remission of 8.6 months. Additionally, this systematic review observed more patients returned to baseline or experienced improvement in symptoms when being treated with a combination of glucocorticoid plus IVIG plus methotrexate.2 Suggested dosing recommendations are available in Table 1.

Patients diagnosed with HMGCR antibody myopathy are contraindicated for future statin therapy.1 Rechallenge of statins in this patient population has led to worsening of disease and therefore these patients should have a severe statin allergy listed in their medical documentation record.
CASE PRESENTATION
A 59-year-old male patient with a medical history including atrial fibrillation, peripheral vascular disease, type 2 diabetes mellitus (T2DM), hypertension, and peripheral neuropathy was referred by his primary care clinical pharmacist practitioner for an outpatient neurology consult. The patient reported a 4-month history of fatigue, lower extremity paresthesia, and progressive proximal muscle weakness which began in his legs, mostly noticeable when walking upstairs but quickly developed into bilateral arm weakness. The patient reported significant impact on his quality of life: he could no longer lift his arms above his head and had difficulty with daily activities such as brushing his hair or getting up from a chair. He reported multiple falls at home, and began to use a cane for assistance with ambulation. He confirmed adherence to atorvastatin over the past year. Laboratory testing on the day of the visit revealed an elevated CPK level at 9729 mcg/L (reference range for men, 30-300 mcg/L).
The patient was urged to go to the emergency department where his CPK level had increased to 12,990 mcg/L (Figure 1). The workup began to find the source of rhabdomyolysis and elevated liver enzymes differentiating autoimmune vs medication-induced myopathy. Upon admission atorvastatin was discontinued, anti-HMGCR antibody level was ordered, and IV fluids were started.

After 8 days of hospital admission with minimal improvement, Rheumatology and Neurology services were consulted in the setting of persistent CPK elevation and the potential neuropathic component of muscle weakness. Both consulting services agreed to consider muscle biopsy and EMG if the patient did not begin to show signs of improvement. The patient’s CPK levels remained elevated with minimal change in muscle weakness. The next step was a right quadricep muscle biopsy performed on Day 14 of admission. Sixteen days after admission, the anti-HMGCR antibody test (originally obtained upon admission) was positive and elevated at 249 CU/mL (reference range, < 20 CU/mL negative; reference range, ≥ 60 CU/mL strong positive), which confirmed the SINAM diagnosis (Table 2).

On Day 17 of hospitalization, the Neurology service initiated IVIG monotherapy to avoid the undesired glycemic AEs associated with glucocorticoids. The patient had a history of T2DM that was difficult to manage and his hemoglobin A1c level was the best it had ever been (6.2%) relative to a peak A1c of 11.0% 9 months prior. The patient was treated with a total IVIG dose of 2 g/kg divided into 3 daily doses while still obtaining CPK levels with daily laboratory tests to assist with trending the extent of disease severity improvement (Figures 2-4). After a 20-day hospital stay, the patient was discharged home with rehabilitation services and a scheduled outpatient EMG the following week.



The patient continued to report generalized body weakness, pain, and deconditioning upon discharge and was unable to attend the EMG neurology appointment. The patient did eventually attend a follow-up appointment about 6 weeks after hospital discharge and reported continued weakness. The Neurology service prescribed a 2-day IVIG regimen (total dose = 2 g/kg) monthly for the next 2 months. The patient returned to the neurology clinic 8 weeks later following 2 rounds of IVIG posthospitalization and reported that his muscle strength was returning, and he was able to slowly reintroduce exercise into his daily routine. During a follow-up appointment about 11 months after the initial hospitalization, the patient’s primary care clinical pharmacist provided education of effective management of cholesterol without statins, including use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors as recommended by the Neurology service. At this time, the patient’s calculated low-density lipoprotein (LDL) was 110 mg/dL (reference range, 0-99 mg/dL). The patient preferred to work on a healthy diet and positive lifestyle choices before trialing any lipid lowering therapies.
The patient appeared to tolerate this treatment regimen following 7 rounds of IVIG. He noted fatigue for about 24 hours after his infusion sessions but otherwise reported no additional AEs. He has continued to attend weekly physical therapy sessions and is able to walk without the assistance of a cane. He can now walk a mile before he begins to feel fatigued or experience bilateral lower leg pain. The pain appears neuropathic in nature, as the patient reports ongoing “pins and needles” sensation in his legs and feet. The patient has noticed a major improvement in his overall function, strength, and exercise tolerance since starting IVIG treatments and although he is not yet back to his baseline, he is motivated to continue his recovery. Neurology is considering ongoing treatment with IVIG monthly infusions given his continued clinical improvement.
DISCUSSION
There is limited evidence on the use of IVIG monotherapy for SINAM, although it may be a viable option for patients deemed poor candidates for glucocorticoid or methotrexate therapy. This particularly applies to patients with DM for which there may be concerns for managing blood glucose levels with steroid use. The Johns Hopkins Myositis Center evaluated 3 patients with SINAM who declined glucocorticoid therapy and had documented DM and weakness in the proximal arms and legs. Following 2 to 3 monthly rounds of IVIG 2 g/kg monotherapy, these patients had reduced CPK levels and had improvement in both arm and hip-flexion strength. Two patients reported no muscle-related symptoms after completing IVIG monotherapy treatment for 9 and 19 months.3
The optimal treatment duration for IVIG monotherapy for SINAM is still uncertain given the limited available data. The patient in this case report showed clinically significant muscle-related improvement following 7 monthly rounds of 2 g/kg IVIG treatments. The mechanism of action for IVIG in this setting is still unknown, although the medication may allow muscle regeneration to surpass muscle destruction, thus leading to resolution of the muscle-related symptoms.3
There are numerous concerns with IVIG use to consider prior to initiating treatment, including expense, AEs, patient response, and comorbidities. IVIG is considerably more expensive than glucocorticoid and methotrexate alternatives. Systemic reactions have been shown to occur in 5% to 15% of patients receiving IVIG infusion.4 The majority of these infusion reactions occur early during infusion or within a few hours after administration is complete.5 Early AEs to monitor for include injection site reactions, flu-like symptoms, dermatologic reactions, anaphylaxis, transfusion-related acute lung injury, and transfusion-associated circulatory overload. Additional AEs may be delayed, including thromboembolic events, acute kidney injury, aseptic meningitis, hemolysis, neutropenia, and blood-borne infection.6 IVIG has a boxed warning for thrombosis, renal dysfunction, and acute renal failure risk.7 There are multiple strategies documented to reduce the risk of IVIG reactions including slowing the infusion rate, ensuring adequate hydration, and/or giving analgesics, antihistamines, or steroids prior to infusion.6 The patient in this case had monthly IVIG infusions without the need of any pretreatment medications and only reported fatigue for about 24 hours following the infusion.
An essential question is how to provide safe cholesterol management for patients with SINAM. Some evidence has suggested that other lipid-lowering medications that avoid the mevalonate pathway, such as fenofibrate or ezetimibe, may be used cautiously initially at lower doses.1 Due to the severity of SINAM, it is crucial to closely monitor and ensure tolerability as new lipid-lowering agents are introduced. More evidence suggests that PCSK9 inhibitors are a safer option.8 PCSK9 inhibitors avoid the mevalonate pathway and block PCSK9 from binding to LDL receptors, allowing LDL to be removed from circulation.
Tiniakou et al followed 8 individuals for a mean 1.5 years who had anti-HMGCR immune-mediated myopathy at high cardiovascular risk. Muscle strength, CPK levels, and serum anti-HMGCR antibody titers were assessed at baseline and again after initiation of PCSK9 inhibitor. None of the patients experienced a decline in their muscle strength. CPK, anti-HMGCR antibody levels, and LDL trended down in all participants and 2 patients were able to reduce their immunosuppression treatment while still achieving clinical improvement. Tiniakou et al suggest that PCSK9 inhibitors are a safe and effective option to lower cholesterol in patients with SINAM.8
Alirocumab is the preferred PCSK9 inhibitor for patients at the US Department of Veterans Affairs (VA). The VA Pharmacy Benefits Management (PBM) Service guidance recommends alirocumab for patients with a history of atherosclerotic cardiovascular disease (ASCVD) or severe hypercholesterolemia.9 PBM guidance suggests alirocumab use for patients with a contraindication, intolerance, or insufficient LDL reduction with a maximally tolerated dose of statin and ezetimibe with a desire to reduce ASCVD risk by lowering LDL. Per the PBM Criteria for Use guidance, patients should follow the stepwise approach and trial ezetimibe prior to being considered for PCSK9 inhibitor therapy. Given the patient’s contraindication to future statin use and severity of myopathy, in this case the Neurology Service felt that the safest option to reach goal LDL reduction would be a PCSK9 inhibitor. Consideration can be made for alirocumab use when considering an alternative lipid lowering therapy.
CONCLUSIONS
This report demonstrates a case of SINAM caused by atorvastatin therapy. Patients presenting with proximal muscle weakness and elevated CPK even after statin discontinuation should be considered for a full workup to determine whether SINAM may be involved. This uncommon form of myopathy can be diagnosed based on the detection of anti-HMGCR antibodies and/or presence of necrosis on muscle biopsy. A combination of glucocorticoid, methotrexate, and IVIG is recommended for a patient’s best chance of muscle symptom improvement. IVIG monotherapy should be considered for patients with glycemic control concerns.
- Tiniakou E. Statin-associated autoimmune myopathy: current perspectives. Ther Clin Risk Manag. 2020;16:483-492. doi:10.2147/TCRM.S197941
- Somagutta MKR, Shama N, Pormento MKL, et al. Statin-induced necrotizing autoimmune myopathy: a systematic review. Reumatologia. 2022;60(1):63-69. doi:10.5114/reum.2022.114108
- Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med. 2015;373(17):1680-1682. doi:10.1056/NEJMc1506163
- Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171-178. doi:10.1016/j.tmrv.2013.05.004
- Ameratunga R, Sinclair J, Kolbe J. Increased risk of adverse events when changing intravenous immunoglobulin preparations. Clin Exp Immunol. 2004;136(1):111-113. doi:10.1111/j.1365-2249.2004.02412.x
- Abbas A, Rajabally YA. Complications of immunoglobulin therapy and implications for treatment of inflammatory neuropathy: a review. Curr Drug Saf. 2019;14(1):3-13. doi:10.2174/1574886313666181017121139
- Privigen. Prescribing information. CSL Behring LLC; 2022. Accessed March 17, 2025. https://labeling.cslbehring.com/PI/US/Privigen/EN/Privigen-Prescribing-Information.pdf
- Tiniakou E, Rivera E, Mammen AL, Christopher-Stine L. Use of proprotein convertase subtilisin/Kexin Type 9 inhibitors in statin-associated immune-mediated necrotizing myopathy: a case series. Arthritis Rheumatol. 2019;71(10):1723-1726. doi:10.1002/art.40919
- US Department of Veterans Affairs, Pharmacy Benefits Management (PBM) Services. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitor) (Alirocumabpreferred, Evolocumab-non-preferred) Criteria for Use. June 2024. Accessed March 25, 2025. https://www.va.gov/formularyadvisor/DOC/128
- Jayatilaka S, Desai K, Rijal S, Zimmerman D. Statin-induced autoimmune necrotizing myopathy. J Prim Care Community Health. 2021;12:21501327211028714. doi:10.1177/21501327211028714
- Tiniakou E. Statin-associated autoimmune myopathy: current perspectives. Ther Clin Risk Manag. 2020;16:483-492. doi:10.2147/TCRM.S197941
- Somagutta MKR, Shama N, Pormento MKL, et al. Statin-induced necrotizing autoimmune myopathy: a systematic review. Reumatologia. 2022;60(1):63-69. doi:10.5114/reum.2022.114108
- Mammen AL, Tiniakou E. Intravenous immune globulin for statin-triggered autoimmune myopathy. N Engl J Med. 2015;373(17):1680-1682. doi:10.1056/NEJMc1506163
- Stiehm ER. Adverse effects of human immunoglobulin therapy. Transfus Med Rev. 2013;27(3):171-178. doi:10.1016/j.tmrv.2013.05.004
- Ameratunga R, Sinclair J, Kolbe J. Increased risk of adverse events when changing intravenous immunoglobulin preparations. Clin Exp Immunol. 2004;136(1):111-113. doi:10.1111/j.1365-2249.2004.02412.x
- Abbas A, Rajabally YA. Complications of immunoglobulin therapy and implications for treatment of inflammatory neuropathy: a review. Curr Drug Saf. 2019;14(1):3-13. doi:10.2174/1574886313666181017121139
- Privigen. Prescribing information. CSL Behring LLC; 2022. Accessed March 17, 2025. https://labeling.cslbehring.com/PI/US/Privigen/EN/Privigen-Prescribing-Information.pdf
- Tiniakou E, Rivera E, Mammen AL, Christopher-Stine L. Use of proprotein convertase subtilisin/Kexin Type 9 inhibitors in statin-associated immune-mediated necrotizing myopathy: a case series. Arthritis Rheumatol. 2019;71(10):1723-1726. doi:10.1002/art.40919
- US Department of Veterans Affairs, Pharmacy Benefits Management (PBM) Services. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9 Inhibitor) (Alirocumabpreferred, Evolocumab-non-preferred) Criteria for Use. June 2024. Accessed March 25, 2025. https://www.va.gov/formularyadvisor/DOC/128
- Jayatilaka S, Desai K, Rijal S, Zimmerman D. Statin-induced autoimmune necrotizing myopathy. J Prim Care Community Health. 2021;12:21501327211028714. doi:10.1177/21501327211028714
Statin-Induced Necrotizing Autoimmune Myopathy in a Patient With Complex Diabetes Management
Statin-Induced Necrotizing Autoimmune Myopathy in a Patient With Complex Diabetes Management