Citations

Objective Long COVID (LC) refers to the long-term symptoms occurring after SARS-CoV-2 infection and resolution of the initial disease prodrome. While LC is increasingly recognized, knowledge about its biomarkers is still limited. This study examines imaging findings in 18 F-FDG PET-CT scans in 40 patients with LC from an academic LC Clinic, for potential imaging biomarkers. Methods This study included patients aged 18 and older with confirmed positive SARS-CoV-2 PCR test and at least 28 days post-symptom onset. 18 F-FDG PET-CT scans were performed, and brain metabolic activity was compared to a control database to generate Z-scores. Participants were grouped based on their clinical phenotype and Z-scores of different brain regions were analyzed using t-tests. Results The study group was mainly female (70%), with a median age of 53 years, and predominantly non-Hispanic White (90%). Most had pre-existing conditions such as gastrointestinal, cardiovascular, endocrine, and psychiatric disorders. The findings showed significant cerebral hypometabolism in 29 patients with fatigue and post-exertional malaise (PEM), particularly in the left sensorimotor cortex (p=0.0253) and bilateral primary visual cortex (right: p=0.0096, left: p=0.0016), which persisted up to two years after infection. Conclusions In summary, this study identified persistent cerebral hypometabolism in LC patients, especially those with fatigue with PEM, up to two years post-infection. These results suggest that 18 F-FDG PET-CT could be a valuable tool for diagnosing and managing LC. Further research is essential to confirm these findings and improve treatment strategies for patients with LC.

ABSTRACT The enteric nervous system (ENS) is a complex peripheral neural network that coordinates gastrointestinal motility through highly organized synaptic communication. Although tissue-resident muscularis macrophages (MMs) closely associate with enteric neurons, whether they regulate enteric synaptic organization remains unknown. In the central nervous system (CNS), microglia sculpt neural circuits through complement-dependent synaptic remodeling, raising the possibility that analogous neuroimmune mechanisms operate in the gut. Here, we identify a previously unrecognized role for C1qa□ MMs in regulating enteric synaptic homeostasis and gastrointestinal motility. Using macrophage-specific constitutive and inducible C1qa deletion models, single-cell RNA sequencing, enteric synaptosome proteomics, physiology, and advanced imaging, we demonstrate that loss of MMs-derived C1qa increases enteric synaptic density without altering neuronal numbers. C1qa deficiency induced broad transcriptional changes in enteric neurons and macrophages, including altered synapse-associated, lysosomal, and endocytic programs. Proteomic analysis revealed that enteric synapses share a conserved molecular architecture with brain synapses while exhibiting distinct gastrointestinal-specific complement-associated synaptic networks enriched for structural and receptor-localization pathways. Functionally, macrophage-specific C1qa deletion altered excitatory and inhibitory enteric neurotransmission, enhanced cholinergic signaling, reduced nitrergic responses, and accelerated gastrointestinal transit, while smooth muscle responsiveness remained preserved. C1qa□ MMs displayed transcriptional and functional features consistent with a phagocytic synapse-remodeling phenotype, including enrichment of complement, lysosomal, and engulfment pathways. Loss of C1qa impaired macrophage phagocytic activity both in vitro and in vivo and was associated with synapse accumulation and altered macrophage morphology. Importantly, inducible deletion of C1qa in adulthood recapitulated the synaptic and motility phenotypes, demonstrating that C1qa□ MMs continuously regulate enteric synaptic organization beyond development. Together, these findings identify a complement-dependent neuroimmune mechanism that regulates enteric circuit organization and gut motility, establishing MMs as active modulators of adult ENS synaptic homeostasis. Abstract Figure

Neuroplastic changes in phrenic motor neurons that underlie recovery from spinal cord injury may be mediated by perineuronal nets. We show that changes in perineuronal nets around phrenic motor neurons occur within 7 days after cervical spinal cord injury, and that the increase in perineuronal nets around larger phrenic motor neurons was more pronounced. These changes are consistent with substantial reorganization of the neural network onto intact phrenic motor neurons following cervical spinal cord injury.

Background: Overlap between diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) is associated with significantly higher mortality than either condition alone. While hypertonic (trans locational) hyponatremia is common in hyperglycemic crises, clinically significant hypernatremia in mixed DKA/HHS presents with certain treatment challenges due to rapid osmotic shifts during insulin therapy. Case presentations: A 40-year-old woman with non-significant past medical history presented with vomiting, polyuria, polydipsia, and confusion for two days. Laboratory evaluation revealed serum glucose 1280 mg/dL, arterial pH 7.214, bicarbonate 13.1 mmol/L, anion gap 24, β-hydroxybutyrate 6.0 mmol/L, corrected sodium 152 mmol/L (measured sodium 133 mmol/L), and calculated effective osmolality 337 mOsm/kg. Initial treatment with isotonic saline and intravenous insulin led to improvement in hyperglycemia but worsening corrected hypernatremia to 160 mmol/L after 3 liters of normal saline. Free water deficit was calculated at 6.3 L. Fluid therapy was transitioned to hypotonic solutions with titration to limit sodium correction to ≤10 mmol/L per 24 hours. Sodium levels gradually normalized with resolution of ketoacidosis, and improvement in mental status without significant neurologic complications. Conclusion: In mixed DKA/HHS, early assessment of corrected sodium and effective osmolality is critical. Insulin-mediated intracellular water shifts may unmask or worsen hypernatremia. Prompt reassessment of corrected sodium and individualized fluid management is needed to avoid treatment-related exacerbation of hypertonicity.

Background Acute otitis externa (AOE) is a common condition encountered in primary care. Evidence-based guidelines recommend topical antimicrobial therapy as first-line treatment for uncomplicated disease regardless of diabetes status. However, clinicians may escalate treatment in patients with diabetes because of concern for necrotizing otitis externa (NOE), a rare but potentially life-threatening complication. This study aimed to evaluate whether diabetes status influences systemic antibiotic use in uncomplicated acute otitis externa and to assess factors associated with treatment decisions. Methods A cross-sectional survey was distributed to primary care clinicians participating in a multi-state primary care practice-based research collaborative, comprising physicians, nurse practitioners, and physician associates within the specialties of family medicine, general pediatrics, and general internal medicine. The survey instrument asked clinicians what they would select as first-line treatment for uncomplicated AOE in patients with and without diabetes mellitus (DM). It also assessed factors influencing management decisions as well as confidence in identifying NOE. The primary outcome was whether the clinician reported they would use systemic antibiotics for treatment of AOE, comparing treatment decisions using relative risk (RR) with 95% confidence intervals (CI) for antibiotic exposure given the presence of DM. Results Out of 257 invitations, 58 respondents completed the survey (22.6%). Systemic antibiotics were selected more frequently when DM was present (19.0%) compared with when DM was absent (5.2%), resulting in a significantly increased likelihood of reported systemic antibiotic use (RR = 3.67; 95% CI, 1.08–12.47; p = 0.043). Clinician confidence in identifying NOE varied, with most respondents reporting only slight or moderate confidence. Conclusions Primary care clinicians reported substantially higher use of systemic antibiotics when managing uncomplicated AOE in patients with DM, representing nearly a fourfold increase in antibiotic exposure despite guideline recommendations favoring topical therapy alone. These findings highlight practice variation which may be driven by concern for necrotizing otitis externa, underscoring opportunities to improve antibiotic stewardship and clinician confidence in risk stratification.