January’s Medical Student Grand Rounds at DHMC, featured four Geisel School of Medicine students who shared a systematic review to determine whether hyperosmolar therapy targeting a specific serum sodium level improves neurological outcomes, examined whether elevated FGF23 is associated with changes in bone structure and function following kidney injury, and tested parameters of nanoscale architecture leading to the development of antifibrotic glaucoma drainage implants to reduce post operative fibrosis.
Here are summaries of their presentations:
How High is Too High? Hypernatremia During Hyperosmolar Therapy for Traumatic Brain Injury
Vishva Natarajan, MS, MED’28 and Angus Mauser MED’28 (not pictured)
Hyperosmolar therapy using hypertonic saline or mannitol is a cornerstone of intracranial pressure management in patients with severe traumatic brain injury (TBI), functioning by increasing serum sodium to create an osmotic gradient that reduces cerebral edema. Despite widespread use and more than 200,000 TBIs annually in the United States, optimal serum sodium targets remain poorly defined, with substantial institutional variability and limited consensus regarding safe upper thresholds.
“Under the guidance of Dr. Perry A. Ball, Section Chief of Neurocritical Care at Dartmouth-Hitchcock Medical Center and professor of surgery and anesthesiology at Geisel, we conducted a systematic review to determine whether hyperosmolar therapy targeting a specific serum sodium level improves neurological outcomes or exposes patients to avoidable harm. After screening 294 articles across four databases, 23 high-quality studies met inclusion criteria for qualitative synthesis.
“Two clinically and biologically distinct patterns emerged. Intentional hypernatremia resulting from clinician-directed hyperosmolar therapy was typically maintained below 150 mmol/L and was associated with lower reported mortality. In contrast, incidental hypernatremia arising from physiologic derangements such as diabetes insipidus, dehydration, or renal dysfunction frequently exceeded 150 mmol/L and was consistently associated with higher mortality and complication rates. Serum sodium levels above 150 mmol/L may therefore represent a clinically meaningful threshold beyond which the risks of hypernatremia outweigh potential intracranial pressure benefits.
“By distinguishing therapeutic sodium targets from pathologic hypernatremia, these findings represent a step forward toward a clinically actionable framework to reduce iatrogenic harm and guide more precise use of hyperosmolar therapy in severe TBI.”
FGF23 as an Endocrine Driver of Bone Loss in Chronic Kidney Disease
Anthony Tsai MED’28
Patients with chronic kidney disease (CKD) have a significantly higher risk of bone fractures compared to the general population, even in early stages of disease. While this skeletal fragility has traditionally been attributed to abnormalities in parathyroid hormone (PTH), calcium, and phosphate balance, these factors do not fully explain the degree of bone loss observed in CKD. This has led researchers to investigate additional mechanisms that may contribute to CKD-related bone disease.
“Fibroblast growth factor 23 (FGF23) is a hormone produced by bone cells that plays a central role in regulating phosphate and vitamin D metabolism through its actions on the kidney. Importantly, FGF23 levels rise very early in CKD—before changes in PTH or serum phosphate are detected—and increase dramatically as kidney function declines. This early and sustained elevation suggests that FGF23 may be more than a compensatory marker of mineral imbalance and may directly contribute to skeletal pathology.
“Our work examined whether elevated FGF23 is associated with changes in bone structure and function following kidney injury. Using a mouse model of kidney disease, we measured kidney function, circulating levels of FGF23 and other mineral metabolism markers, and performed detailed analysis of bone microarchitecture and bone formation activity. We found that bone loss, impaired mineralization, and reduced osteoblast activity occurred early in disease progression and closely paralleled elevations in FGF23, even when PTH and phosphate levels were not markedly abnormal.
“These findings support the idea that FGF23 may act as an endocrine driver of bone loss in CKD. Understanding how FGF23 directly affects bone may help explain fracture risk in CKD and identify new therapeutic targets beyond traditional treatments focused on PTH and mineral balance.”
Developing antifibrotic glaucoma drainage implants using nanoscale surface architecture
Parker Scott MED’27
Glaucoma is the world’s leading cause of blindness. This chronic progressive damage to the optic nerve is painless and often goes unnoticed until more moderate or severe stages. People often refer to glaucoma as the “Silent Thief of Sight” because of this.
“While we have effective treatments in early and mild cases of glaucoma, the surgical interventions we use for moderate or severe glaucoma have incredibly high (30-50%) failure rates often requiring additional surgeries and implants. For some patients, we may even run out of surgical options as the real estate for surgical implants and interventions in the eye is small forcing us to manage eyes on a form of eye hospice as any remaining vision in that eye is lost. The major cause of failure in these surgical interventions is postoperative fibrosis.
“One common surgical intervention is the implant of a small smooth inert glaucoma drainage tube that increases the drainage of fluid in the eye lowering the intraocular pressure (the goal of all treatments of glaucoma). The goal of my research is to develop a tube that reduces post operative fibrosis by incorporating a nanoscale surface architecture that mimics that surrounding collagen extracellular matrix resulting in a reduced fibrotic foreign body response. In my project, I tested various parameters of this nanoscale architecture including varying nanofiber diameters, porosity, material etc. We found that nanofibers of all sizes reduce aSMA expression (a measure of fibrosis) when compared to smooth control materials. We also found that certain porosity increases integration of cells and have thinner fibrous capsules compared to other nanomaterials. More research is ongoing to determine the optimal parameters of the nanofiber material that we will incorporate into a glaucoma drainage tube to test in vivo.”
This project is under the guidance of Ian Pitha MED’07, PhD’04 at the Moran Eye Center at the University of Utah.
