Endoscopic Endonasal Transsphenoidal Surgery for the Resection of Pituitary Adenomas: A Prime Candidate for a Shortened Length of Stay Enhanced Recovery after Surgery Protocol? A Systematic Review.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a perioperative model of care aimed at optimizing postoperative rehabilitation and reducing hospital length of stay (LOS). Decreasing LOS avoids hospital-acquired complications, reduces cost of care, and improves patient satisfaction. Given the lack of ERAS protocols for endoscopic endonasal transsphenoidal surgery (EETS) resection of pituitary adenomas, a systematic review of EETS was performed to compile patient outcomes and analyze factors that may lead to increased LOS, reoperation, and readmission rates with the intention to contribute to the development of a successful ERAS protocol for EETS. METHODS: The authors performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines-based systematic review of the literature. Information was extracted regarding patient LOS, surgery complications, and readmission/reoperation rates. Pearson's correlations to LOS and reoperation/readmission rates were performed with variables normalized to the number of participants. Statistical significance was set at P value <0.05. RESULTS: Fourteen studies were included, consisting of 2083 patients. The most common complications were cerebrospinal fluid leaks (37%) and postoperative diabetes insipidus (DI) (9%). Transient DI was significantly correlated with shorter LOS. Functional pituitary adenomas were significantly correlated with lower readmission rates while nonfunctional pituitary adenomas were correlated with higher readmission rates. No other factor was found to be significantly correlated with a change in LOS or reoperation rate. CONCLUSIONS: EETS may be an ideal candidate for the development of ERAS cranial protocols. While our data largely supports the safe implementation of shortened LOS protocols in EETS, our findings highlight the importance of transient DI and nonfunctional pituitary adenomas management when formulating ERAS protocols.

Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome.

Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by a deficiency in sphingosine-1-phosphate lyase (SPL), the final enzyme in the sphingolipid degradative pathway. Inactivating mutations of SGPL1-the gene encoding SPL-lead to a deficiency of its downstream products, and buildup of sphingolipid intermediates, including its bioactive substrate, sphingosine-1-phosphate (S1P), the latter causing lymphopenia, a hallmark of the disease. Other manifestations of SPLIS include nephrotic syndrome, neuronal defects, and adrenal insufficiency, but their pathogenesis remains unknown. In this report, we describe the correlation between SGPL1 genotypes, age at diagnosis, and patient outcome. Vitamin B6 serves as a cofactor for SPL. B6 supplementation may aid some SPLIS patients by overcoming poor binding kinetics and promoting proper folding and stability of mutant SPL proteins. However, this approach remains limited to patients with a susceptible allele. Gene therapy represents a potential targeted therapy for SPLIS patients harboring B6-unresponsive missense mutations, truncations, deletions, and splice-site mutations. When Sgpl1 knockout (SPLKO) mice that model SPLIS were treated with adeno-associated virus (AAV)-mediated SGPL1 gene therapy, they showed profound improvement in survival and kidney and neurological function compared to untreated SPLKO mice. Thus, gene therapy appears promising as a universal, potentially curative treatment for SPLIS.