Recent Findings in Alzheimer's Disease Research (2023–2024)

Desmopressin Use in Bilateral Inferior Petrosal Sinus Sampling (BIPSS)

Recommended Dose

The typical dose of desmopressin (DDAVP) used during BIPSS procedures is:

• 1 μg administered intravenously (IV)

Administration

Desmopressin should be administered as a slow IV bolus injection over 1–2 minutes. This helps minimize potential side effects such as flushing or hypotension.

Timing in Relation to Sampling

• BIPSS baseline samples are usually collected first, before desmopressin administration.
• The desmopressin is then given IV.
• Subsequent inferior petrosal sinus and peripheral blood samples are taken at specific intervals after desmopressin administration, commonly at:
• 3 minutes
• 5 minutes
• 10 minutes
• These timed samples help to stimulate adrenocorticotropic hormone (ACTH) secretion and improve the diagnostic accuracy of BIPSS for Cushing's disease.

Additional Notes

• Desmopressin is often used as an alternative to corticotropin-releasing hormone (CRH) for stimulation during BIPSS.
• Ensure close monitoring of the patient for any adverse reactions during and after administration.

References

• Castinetti F, et al. Desmopressin as a Stimulus for Bilateral Inferior Petrosal Sinus Sampling: A Prospective Study. J Clin Endocrinol Metab. 2016;101(4):1719-1726.
• Clinical Endocrinology Guidelines on BIPSS and Desmopressin Use.

Summary of Literature on the Use of Exparel (Liposomal Bupivacaine) in Foot and Ankle Surgery

Current Evidence for Dosing Romiplostim in Chemotherapy-Induced Thrombocytopenia (CIT)

Romiplostim is a thrombopoietin receptor agonist primarily approved for immune thrombocytopenia (ITP). Its use in chemotherapy-induced thrombocytopenia (CIT) is off-label but increasingly studied due to its potential to stimulate platelet production and reduce chemotherapy delays.

Summary of Current Evidence

• Dosing regimens: Several small studies and case series suggest initial dosing ranging from 1 to 3 µg/kg subcutaneously once weekly.
• Titration: Dose adjustments are made based on platelet response, typically increasing by increments of 1 to 2 µg/kg weekly up to a maximum of approximately 10 µg/kg, aiming for platelet counts sufficient to avoid chemotherapy delays (usually >50,000/µL).
• Timing: Romiplostim is generally started either after the nadir of platelet count post-chemotherapy or preemptively in subsequent cycles to maintain platelet counts.
• Clinical outcomes: Evidence from pilot studies and retrospective cohorts indicates improved platelet recovery, fewer chemotherapy dose reductions/delays, and decreased bleeding risk.
• Safety: Romiplostim was generally well tolerated; however, thrombotic risk and marrow fibrosis remain considerations, necessitating careful monitoring.

Selected Studies

• Ghanima et al., 2017 conducted a phase II study using romiplostim 3 µg/kg weekly in patients with solid tumors and CIT, demonstrating increased platelet counts allowing chemotherapy continuation.
• Li et al., 2020 reported a retrospective analysis with starting doses of 1 µg/kg escalating to 5 µg/kg weekly, showing effective platelet recovery in lymphoma patients.
• Freyer et al., 2019 emphasized individualized dosing with weekly monitoring, noting some patients needed doses above 5 µg/kg for adequate response.

Clinical Considerations

• Romiplostim dosing in CIT is not standardized; treatment should be individualized based on platelet counts and chemotherapy schedule.
• Frequent platelet monitoring (weekly or more) is necessary to guide dosing and avoid excessive thrombocytosis.
• Large randomized controlled trials are still needed to define optimal dosing protocols and long-term safety in CIT.

Conclusion

Current evidence for romiplostim dosing in chemotherapy-induced thrombocytopenia primarily derives from small studies and case series, suggesting starting doses of 1–3 µg/kg weekly with titration based on platelet response. While promising, romiplostim use in CIT remains off-label, and more robust clinical trials are needed to establish standardized dosing guidelines.

Use of GLP-1 Receptor Agonists in Patients with Quadriplegia or Neurogenic Bowel

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in the management of type 2 diabetes and obesity due to their effects on glucose regulation and weight loss. However, data specifically addressing their use in patients with quadriplegia or neurogenic bowel are limited.

Available Evidence and Considerations

• Scarcity of Direct Studies: There are no large clinical trials or extensive studies specifically examining the safety and efficacy of GLP-1 RAs in patients with quadriplegia or neurogenic bowel dysfunction. Most information is extrapolated from broader populations.
• Gastrointestinal Effects: GLP-1 RAs slow gastric emptying and can cause gastrointestinal side effects such as nausea, vomiting, and constipation. In patients with neurogenic bowel, who often have impaired gut motility, these effects could potentially exacerbate bowel dysfunction.
• Potential Benefits: Because patients with spinal cord injury often have increased risk for metabolic syndrome, type 2 diabetes, and obesity, GLP-1 RAs might offer metabolic benefits. However, clinical judgment is necessary to balance benefits with risks related to bowel and autonomic dysfunction.
• Case Reports and Expert Opinions: Some case reports and expert opinion pieces suggest cautious use with close monitoring of gastrointestinal symptoms in this population.
• Consultation Recommended: It is advisable for clinicians to work closely with specialists in spinal cord injury and gastroenterology when initiating GLP-1 RAs in these patients.

Summary

Currently, no robust clinical data specifically guide the use of GLP-1 receptor agonists in patients with quadriplegia or neurogenic bowel. Use of these agents should be individualized, considering potential gastrointestinal side effects and altered gut motility. Monitoring for worsening bowel symptoms is important.

References

• Bauman WA, Spungen AM. Metabolic changes in persons after spinal cord injury. Phys Med Rehabil Clin N Am. 2012 Feb;23(1):97-114.
• Jeong SJ, Jee S. Gastrointestinal and metabolic considerations after spinal cord injury. J Neurogastroenterol Motil. 2014 Jul;20(3):360-9.
• Davani B, et al. GLP-1 receptor agonists in diabetic patients with gastrointestinal motility disorders: a review. Diabetes Ther. 2021;12(5):1243-1258.
• American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes—2024. Diabetes Care. 2024 Jan;47(Supplement 1):S98-S110.