Clinical Commander

Back to dossier
ent.acute-sinusitis.core.v1PRODUCTION
ent.acute-sinusitis.core.v1

Acute rhinosinusitis (viral vs ABRS; complications)

general_internal_medicineacutesubacuteadultpediatric
Hard-required inputs
0 / 11
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame as ACUTE rhinosinusitis (<4 wk) and set the two decisive questions: (1) viral ARS vs ABRS by symptom duration/trajectory (>90-98% of ARS is viral; ~0.5-2% of viral URI becomes ABRS — Payne AAO-HNS 2025; Chow IDSA 2012); (2) uncomplicated vs complicated (orbital/intracranial emergency). Chronic rhinosinusitis (≥12 wk) and headache/dental mimics are differentiated, not re-managed; complications are recognised then routed OUT by engine_id.

Inputs
0
Actions
0
Advance rule
Set
Advance when

ARS scope confirmed; CRS and complication/mimic pathways routed by engine_id, not re-authored

Patient inputs (15)

Purulent (vs clear/watery) discharge is a cardinal ARS symptom and one limb of the severe-onset criterion; purulence resolves faster on antibiotics (Lemiengre Cochrane 2018 PMID 30198548; Chow IDSA 2012)

Unilateral maxillary/facial pain with tenderness and worse-on-bending favours ABRS over viral ARS; midfacial location also pivots vs migraine/dental causes (EPOS 2020 PMID 32077450; Chow IDSA 2012)

High fever (≥39 °C) with purulence for ≥3-4 d defines severe-onset ABRS; persistent high fever also flags possible complication (Chow IDSA 2012 PMID 22438350; Wald AAP 2013 PMID 23796742)

Pediatric ABRS uses a distinct triad and the observe-3-days option for persistent illness (Wald AAP 2013); age also weights resistance risk and dosing (Wald AAP 2013 PMID 23796742; Chow IDSA 2012)

Duration is the single strongest viral-vs-ABRS discriminator: <10 d improving = viral; ≥10 d without improvement = persistent ABRS pattern (Chow IDSA 2012; Payne AAO-HNS 2025; Young Lancet 2008)

Trajectory shape (steadily improving vs persistent-no-improvement vs double-sickening vs severe-onset) defines which of the three ABRS clinical patterns applies (Chow IDSA 2012 PMID 22438350; EPOS 2020 PMID 32226949)

Periorbital oedema vs proptosis / ophthalmoplegia / diplopia / reduced acuity / RAPD distinguishes preseptal from orbital cellulitis/abscess — vision-threatening; route OUT to ophtho.orbital-cellulitis.core.v1 (Payne AAO-HNS 2025; Chow IDSA 2012)

Severe/worsening frontal headache, meningism, photophobia, vomiting, seizure, altered mentation, focal deficit, or forehead swelling (Pott's puffy tumour) → route OUT to neuro.bacterial-meningitis.core.v1 (Chow IDSA 2012 PMID 22438350)

Neutropenia, transplant, haematologic malignancy, poorly controlled diabetes (DKA) → acute invasive fungal rhinosinusitis (mucormycosis/Aspergillus) — a rapidly fatal emergency with a completely different pathway (EPOS 2020 PMID 32077450; Chow IDSA 2012)

Penicillin allergy gates first-line amoxicillin ± clavulanate → doxycycline or a respiratory fluoroquinolone substitute (Payne AAO-HNS 2025 PMID 40742114; Chow IDSA 2012)

Antibiotic use within 4-6 weeks, age <2 or >65, prior hospitalisation, immunocompromise, severe illness → high-dose amoxicillin-clavulanate (resistance-risk pathway) (Chow IDSA 2012 PMID 22438350)

NOT for routine ARS diagnosis (Payne AAO-HNS 2025 — strong recommendation against imaging in uncomplicated ARS); contrast CT only when an orbital/intracranial complication or alternative diagnosis is suspected (Payne AAO-HNS 2025 PMID 40742114; Wald AAP 2013)

Strictly unilateral pain, photophobia/phonophobia/aura (migraine), maxillary dental pain/percussion-tender tooth (odontogenic), or unilateral foul discharge + epistaxis + cheek numbness (invasive fungal/neoplasm) pivots the ARS look-alike differential (EPOS 2020 PMID 32077450)

Pregnancy/lactation gates antibiotic and adjunct safety: avoid doxycycline and fluoroquinolones; amoxicillin ± clavulanate preferred (Payne AAO-HNS 2025 PMID 40742114)

Renal function for amoxicillin-clavulanate / levofloxacin dose adjustment (race-free eGFR) (Chow IDSA 2012; Inker NEJM 2021)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningorbital_cellulitis_or_abscess_route_out
    Proptosis, painful or restricted eye movement, diplopia, reduced visual acuity/colour vision, RAPD, or marked periorbital oedema with systemic features — orbital cellulitis or subperiosteal/orbital abscess (Payne AAO-HNS 2025 PMID 40742114; Chow IDSA 2012 PMID 22438350)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningintracranial_extension_route_out
    Severe/worsening frontal headache, meningism, photophobia, vomiting, seizure, altered mentation, or focal neurologic deficit with a sinus source — meningitis, epidural/subdural empyema, brain abscess, or venous sinus thrombosis (Chow IDSA 2012 PMID 22438350)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningpotts_puffy_tumor
    Doughy, tender forehead/scalp swelling over the frontal bone with frontal sinusitis — Pott's puffy tumour (frontal bone osteomyelitis with subperiosteal abscess), high risk of concurrent intracranial extension (Chow IDSA 2012 PMID 22438350)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningcavernous_sinus_thrombosis
    Bilateral/progressive periorbital oedema, ophthalmoplegia (CN III/IV/VI), proptosis, ptosis, V1/V2 sensory loss, with severe headache and toxicity following sphenoid/ethmoid sinusitis — septic cavernous sinus thrombosis (Chow IDSA 2012 PMID 22438350)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningacute_invasive_fungal_rhinosinusitis
    Immunocompromised (neutropenia, transplant, haematologic malignancy) or poorly controlled diabetes/DKA with facial pain, nasal eschar, anaesthetic or necrotic mucosa, rapidly progressive orbital/CNS findings — acute invasive fungal rhinosinusitis (mucormycosis / Aspergillus) (EPOS 2020 PMID 32077450; Chow IDSA 2012 PMID 22438350)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresystemic_toxicity_route_to_sepsis
    qSOFA ≥2, hypotension on adequate fluids, or NEWS2 high-score systemic toxicity with a complicated-sinusitis source (SSC 2021; RCP NEWS2 2017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateabrs_treatment_failure_reassessment
    No improvement by 7 days from diagnosis (adults; 72 h pediatric) or worsening at any point on the chosen management (watchful waiting or first-line antibiotic) (Payne AAO-HNS 2025 PMID 40742114; Wald AAP 2013 PMID 23796742)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RED_FLAGSrequiredDrives screening
Loading…

Recommended regimen

Acute rhinosinusitis — watchful-waiting-first ladder (viral ARS → uncomplicated ABRS → penicillin-allergy → complicated/IV)
axis: abrs_watchful_waiting_firststep 1 - Step 1 — Viral ARS / shared-decision watchful waiting (NO antibiotic) + symptomatic adjuncts
Selected step "Step 1 — Viral ARS / shared-decision watchful waiting (NO antibiotic) + symptomatic adjuncts" — ARS without an ABRS pattern (improving, <10 d, no double-sickening, no severe onset) OR uncomplicated ABRS where watchful waiting is chosen via shared decision-making (2025 AAO-HNS extends watchful waiting to ALL uncomplicated ABRS regardless of severity)
  • watchful_waiting_no_antibiotic_with_7day_safety_net
    first line
    decision_gate
    triggers: viral_ars_pattern, uncomplicated_abrs_shared_decision
    Payne AAO-HNS 2025 (PMID 40742114) — watchful waiting (symptomatic care + safety-net follow-up if not improving by 7 d or worsening) for ALL uncomplicated ABRS; Lemiengre Cochrane 2018 (PMID 30198548) — ~46% cured at 1 wk / ~64% at 14 d without antibiotics; antibiotic NNTB ~19 (clinical dx), NNH ~8
  • intranasal_corticosteroid_eg_fluticasone_or_mometasone
    add on
    intranasal_corticosteroid
    triggers: symptom_relief_any_ars
    Payne AAO-HNS 2025 / EPOS 2020 (PMID 32077450) — intranasal corticosteroid is an option for symptom relief in viral ARS and ABRS (modest benefit, faster symptom resolution); RxCUI deferred — multiple branded INS products, no single confident MIN
  • isotonic_saline_nasal_irrigation
    add on
    nasal_saline
    triggers: symptom_relief_any_ars
    Payne AAO-HNS 2025 / EPOS 2020 — saline irrigation/spray is a low-harm symptomatic option for ARS
  • acetaminophen
    add on
    analgesic_antipyretic
    650-1000 mg • PO • q6h PRN (max: max 3-4 g/day)
    triggers: pain, fever
    Payne AAO-HNS 2025 — analgesics/antipyretics for pain and fever in viral ARS and ABRS (NSAID alternative if no contraindication)
    rxcui 161

outpatient playbook — drug actions (4)

  1. 1. watchful waiting + symptomatic adjuncts (no antibiotic)
    INS + saline + analgesia • intranasal/PO • as directed
    trigger: Viral ARS or uncomplicated ABRS with watchful waiting chosen (shared decision) (Payne AAO-HNS 2025)
    Most ARS is viral; antibiotic benefit marginal (NNTB ~19, NNH ~8 — Lemiengre Cochrane 2018)
  2. 2. amoxicillin-clavulanate (first-line if treating)
    rxcui 19711
    875/125 mg • PO • BID × 5-10 d
    trigger: ABRS + antibiotic chosen or watchful-waiting failure at 7 d (Payne AAO-HNS 2025; Chow IDSA 2012)
    First-line amoxicillin ± clavulanate; high-dose if resistance risk
  3. 3. doxycycline (penicillin allergy)
    rxcui 3640
    100 mg • PO • BID × 5-7 d
    trigger: ABRS requiring antibiotic + penicillin allergy, not pregnant, age ≥8 (Chow IDSA 2012)
    Preferred penicillin-allergy alternative
  4. 4. levofloxacin (penicillin allergy, doxycycline unsuitable)
    rxcui 82122
    500-750 mg • PO • once daily × 5-10 d
    trigger: Penicillin allergy where doxycycline unsuitable (Chow IDSA 2012)
    Reserve respiratory fluoroquinolone — tendon/QT/CNS risk

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Nasal obstruction/congestion + anterior or posterior purulent discharge + facial pain/pressure/fullness (cardinal ARS symptom cluster; ≥2 of these = rhinosinusitis) (Payne AAO-HNS 2025 PMID 40742114; EPOS 2020 PMID 32077450); URI-type symptoms persisting ≥10 days WITHOUT improvement — the persistent-illness ABRS pattern (Chow IDSA 2012 PMID 22438350; Wald AAP 2013 PMID 23796742); "Double-sickening" — new fever / worsening discharge / worsening facial pain after an initially improving URI (Chow IDSA 2012 PMID 22438350; EPOS 2020 PMID 32226949).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Acute rhinosinusitis (viral vs ABRS; complications)** (ent.acute-sinusitis.core.v1).
Phenotype framing: Terminal ARS differential with explicit pivots: viral ARS (<10 d, improving, no double-sickening — pivot: trajectory) vs ABRS (≥10 d no improvement OR double-sickening OR severe onset — pivot: duration/trajectory + purulence + fever) vs migraine ("sinus headache" — pivot: unilateral throbbing + photophobia/phonophobia + aura + no purulence; route to neuro.migraine.core.v1) vs tension-type headache (bilateral band, no nasal signs) vs odontogenic/dental sinusitis (maxillary, percussion-tender tooth, unilateral foul discharge — pivot: dental source) vs acute invasive fungal rhinosinusitis (immunocompromised/DKA + necrotic eschar/anaesthetic mucosa + orbital/CNS findings — pivot: host + necrosis) vs CRS (≥12 wk — pivot: duration) vs neoplasm (unilateral, epistaxis, cheek numbness, refractory).
Scope: Frame as ACUTE rhinosinusitis (<4 wk) and set the two decisive questions: (1) viral ARS vs ABRS by symptom duration/trajectory (>90-98% of ARS is viral; ~0.5-2% of viral URI becomes ABRS — Payne AAO-HNS 2025; Chow IDSA 2012); (2) uncomplicated vs complicated (orbital/intracranial emergency). Chronic rhinosinusitis (≥12 wk) and headache/dental mimics are differentiated, not re-managed; complications are recognised then routed OUT by engine_id.

No severity triggers fired against current inputs.

Plan

Regimen axis: **Acute rhinosinusitis — watchful-waiting-first ladder (viral ARS → uncomplicated ABRS → penicillin-allergy → complicated/IV)** — step "Step 1 — Viral ARS / shared-decision watchful waiting (NO antibiotic) + symptomatic adjuncts".
1. watchful_waiting_no_antibiotic_with_7day_safety_net (decision_gate, first line) — Payne AAO-HNS 2025 (PMID 40742114) — watchful waiting (symptomatic care + safety-net follow-up if not improving by 7 d or worsening) for ALL uncomplicated ABRS; Lemiengre Cochrane 2018 (PMID 30198548) — ~46% cured at 1 wk / ~64% at 14 d without antibiotics; antibiotic NNTB ~19 (clinical dx), NNH ~8
2. intranasal_corticosteroid_eg_fluticasone_or_mometasone (intranasal_corticosteroid, add on) — Payne AAO-HNS 2025 / EPOS 2020 (PMID 32077450) — intranasal corticosteroid is an option for symptom relief in viral ARS and ABRS (modest benefit, faster symptom resolution); RxCUI deferred — multiple branded INS products, no single confident MIN
3. isotonic_saline_nasal_irrigation (nasal_saline, add on) — Payne AAO-HNS 2025 / EPOS 2020 — saline irrigation/spray is a low-harm symptomatic option for ARS
4. acetaminophen 650-1000 mg PO q6h PRN (analgesic_antipyretic, add on) — Payne AAO-HNS 2025 — analgesics/antipyretics for pain and fever in viral ARS and ABRS (NSAID alternative if no contraindication)

Setting playbook (outpatient) — Discriminate viral ARS from ABRS by duration/trajectory, exclude orbital/intracranial complications, apply shared-decision watchful waiting vs antibiotic, start symptomatic adjuncts, and book a 7-day safety-net (Payne AAO-HNS 2025 PMID 40742114; Chow IDSA 2012 PMID 22438350)
5. watchful waiting + symptomatic adjuncts (no antibiotic) INS + saline + analgesia intranasal/PO as directed — Viral ARS or uncomplicated ABRS with watchful waiting chosen (shared decision) (Payne AAO-HNS 2025) (Most ARS is viral; antibiotic benefit marginal (NNTB ~19, NNH ~8 — Lemiengre Cochrane 2018))
6. amoxicillin-clavulanate (first-line if treating) 875/125 mg PO BID × 5-10 d — ABRS + antibiotic chosen or watchful-waiting failure at 7 d (Payne AAO-HNS 2025; Chow IDSA 2012) (First-line amoxicillin ± clavulanate; high-dose if resistance risk)
7. doxycycline (penicillin allergy) 100 mg PO BID × 5-7 d — ABRS requiring antibiotic + penicillin allergy, not pregnant, age ≥8 (Chow IDSA 2012) (Preferred penicillin-allergy alternative)
8. levofloxacin (penicillin allergy, doxycycline unsuitable) 500-750 mg PO once daily × 5-10 d — Penicillin allergy where doxycycline unsuitable (Chow IDSA 2012) (Reserve respiratory fluoroquinolone — tendon/QT/CNS risk)

Non-pharmacologic actions:
- Saline nasal irrigation/spray + intranasal corticosteroid for symptom relief (Payne AAO-HNS 2025)
- Counsel viral ARS natural history (~10-14 d) and antibiotic stewardship (Lemiengre Cochrane 2018)
- Safety-net: return if not improving by 7 d, worsening at any time, or any orbital/neurologic sign (Payne AAO-HNS 2025)
- Delayed-prescription option as a stewardship tool (EPOS 2020)

AVOID / contraindication checks:
- No antibiotic for viral ars or uncomplicated ars when watchful waiting chosen (Payne AAO HNS 2025 PMID 40742114; Lemiengre Cochrane 2018 PMID 30198548 — marginal benefit, NNH ~8)
- Doxycycline avoid pregnancy lactation and children under 8 (Chow IDSA 2012 PMID 22438350)
- Fluoroquinolone reserve tendon QT CNS aortic avoid pregnancy children (FDA boxed warnings; Payne AAO HNS 2025 judicious use)
- Penicillin allergy blocks amoxicillin and amox clav use doxycycline or fluoroquinolone (Chow IDSA 2012)
- Amoxicillin clavulanate and levofloxacin renal dose adjust by eGFR (Chow IDSA 2012; Inker NEJM 2021)
- Complicated abrs and invasive fungal route out not managed here (Chow IDSA 2012 — orbital/intracranial/fungal emergencies routed by engine_id)

Monitoring

Regimen monitoring:
- reassess at 7 days from diagnosis or sooner if worsening (Payne AAO-HNS 2025 PMID 40742114; Wald AAP 2013 PMID 23796742 — 72 h pediatric)
- confirm abrs exclude complication and alternative at reassessment (Payne AAO-HNS 2025)
- expected natural history viral ars resolves 10 to 14 days counsel before escalation (Lemiengre Cochrane 2018 PMID 30198548)
- orbital or neurologic change at any time triggers immediate contrast CT and route out (Chow IDSA 2012 PMID 22438350)

Setting (outpatient) monitoring:
- Reassess at 7 days from diagnosis or sooner if worsening (Payne AAO-HNS 2025)
- Pediatric: reassess within 72 h of initial management (Wald AAP 2013)
- Return precautions: orbital swelling, vision change, severe/worsening headache, neck stiffness, altered mentation (Chow IDSA 2012)

Follow-up plan: Educate on natural history (viral ARS self-limited; antibiotic NNT ~11-15, NNH ~8 for adverse effects — Lemiengre Cochrane 2018; Young Lancet 2008) and antibiotic stewardship. Define recurrence (≥4 ABRS episodes/yr with symptom-free intervals) and the CRS boundary (symptoms ≥12 wk with objective sinonasal inflammation → CRS pathway / ENT referral). Return precautions: orbital swelling, visual change, severe/worsening headache, neck stiffness, altered mentation → emergency re-presentation. ENT referral for recurrent ARS, complications, anatomic factors, immunodeficiency, or chronic transition.
- Close-out criterion: natural-history + stewardship counselling done; recurrence/CRS boundary defined; ENT referral made if criteria met

Monitoring phase: Reassess at 7 days from diagnosis (Payne AAO-HNS 2025) — or sooner / within 72 h if worsening (Wald AAP 2013): confirm ABRS, exclude an evolving complication or alternative diagnosis, and detect treatment failure. Counsel that most viral ARS resolves within ~10-14 days and ~46% of ARS is cured by 1 wk / ~64% by 14 d WITHOUT antibiotics (Lemiengre Cochrane 2018). Worsening orbital/neurologic signs at any time → immediate contrast CT + route OUT.

Disposition

Current setting: outpatient — Discriminate viral ARS from ABRS by duration/trajectory, exclude orbital/intracranial complications, apply shared-decision watchful waiting vs antibiotic, start symptomatic adjuncts, and book a 7-day safety-net (Payne AAO-HNS 2025 PMID 40742114; Chow IDSA 2012 PMID 22438350)

Disposition criteria:
- Discharge with symptomatic care ± prescription + 7-day safety-net if uncomplicated (Payne AAO-HNS 2025)
- Admit + route OUT if complicated, toxic, or invasive fungal suspected (Chow IDSA 2012)

Escalation triggers (move to higher acuity):
- Orbital signs (proptosis/ophthalmoplegia/acuity loss) → ED + contrast CT + route to ophtho.orbital-cellulitis.core.v1 (Payne AAO-HNS 2025)
- Intracranial signs (meningism/altered mentation/Pott's puffy) → ED + contrast CT + route to neuro.bacterial-meningitis.core.v1 (Chow IDSA 2012)
- Systemic toxicity / qSOFA ≥2 → route to id.sepsis.core.v1 (SSC 2021)
- Immunocompromised/DKA + facial pain/eschar → emergent ENT for invasive fungal rhinosinusitis (EPOS 2020)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Proptosis, painful or restricted eye movement, diplopia, reduced visual acuity/colour vision, RAPD, or marked periorbital oedema with systemic features — orbital cellulitis or subperiosteal/orbital abscess (Payne AAO-HNS 2025 PMID 40742114; Chow IDSA 2012 PMID 22438350)
- [LIFE_THREATENING] Severe/worsening frontal headache, meningism, photophobia, vomiting, seizure, altered mentation, or focal neurologic deficit with a sinus source — meningitis, epidural/subdural empyema, brain abscess, or venous sinus thrombosis (Chow IDSA 2012 PMID 22438350)
- [LIFE_THREATENING] Doughy, tender forehead/scalp swelling over the frontal bone with frontal sinusitis — Pott's puffy tumour (frontal bone osteomyelitis with subperiosteal abscess), high risk of concurrent intracranial extension (Chow IDSA 2012 PMID 22438350)

Citations

- AAO-HNS Clinical Practice Guideline: Adult Sinusitis Update 2025 (Payne et al, Otolaryngol Head Neck Surg, PMID 40742114; executive summary 40741969 — CURRENT US authority, REPLACES Rosenfeld 2015 PMID 25832968) + IDSA 2012 Acute Bacterial Rhinosinusitis (Chow et al, CID, PMID 22438350) + EPOS 2020 European Position Paper on Rhinosinusitis (Fokkens et al, Rhinology, PMID 32077450; exec 32226949) + AAP Pediatric Acute Bacterial Sinusitis 2013 (Wald et al, Pediatrics, PMID 23796742) + Cochrane antibiotics for acute rhinosinusitis (Lemiengre 2018, PMID 30198548) + Young IPD meta-analysis (Lancet 2008, PMID 18342685) [PMID:40742114](https://pubmed.ncbi.nlm.nih.gov/40742114/)
- Cited evidence (PMID 40741969) [PMID:40741969](https://pubmed.ncbi.nlm.nih.gov/40741969/)
- Cited evidence (PMID 22438350) [PMID:22438350](https://pubmed.ncbi.nlm.nih.gov/22438350/)
- Cited evidence (PMID 25832968) [PMID:25832968](https://pubmed.ncbi.nlm.nih.gov/25832968/)
- Cited evidence (PMID 32077450) [PMID:32077450](https://pubmed.ncbi.nlm.nih.gov/32077450/)

Last reconciled with current guidelines: 2026-05-17.
References
  • AAO-HNS Clinical Practice Guideline: Adult Sinusitis Update 2025 (Payne et al, Otolaryngol Head Neck Surg, PMID 40742114; executive summary 40741969 — CURRENT US authority, REPLACES Rosenfeld 2015 PMID 25832968) + IDSA 2012 Acute Bacterial Rhinosinusitis (Chow et al, CID, PMID 22438350) + EPOS 2020 European Position Paper on Rhinosinusitis (Fokkens et al, Rhinology, PMID 32077450; exec 32226949) + AAP Pediatric Acute Bacterial Sinusitis 2013 (Wald et al, Pediatrics, PMID 23796742) + Cochrane antibiotics for acute rhinosinusitis (Lemiengre 2018, PMID 30198548) + Young IPD meta-analysis (Lancet 2008, PMID 18342685) — PMID:40742114
  • Cited evidence (PMID 40741969) — PMID:40741969
  • Cited evidence (PMID 22438350) — PMID:22438350
  • Cited evidence (PMID 25832968) — PMID:25832968
  • Cited evidence (PMID 32077450) — PMID:32077450