Daniel Zeitouni

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest cancers with a dismal 7% 5-year survival rate and is projected to become the second leading cause of cancer-related deaths by 2020. KRAS is mutated in 95% of PDACs and is a well-validated driver of PDAC growth and maintenance. However, despite comprehensive efforts, an effective anti-RAS drug has yet to reach the clinic. Different paths to inhibiting RAS signaling are currently under investigation in the hope of finding a successful treatment. Recently, direct RAS binding molecules have been discovered, challenging the perception that RAS is an "undruggable" protein. Other strategies currently being pursued take an indirect approach, targeting proteins that facilitate RAS membrane association or downstream effector signaling. Unbiased genetic screens have identified synthetic lethal interactors of mutant RAS. Most recently, metabolic targets in pathways related to glycolytic signaling, glutamine utilization, autophagy, and macropinocytosis are also being explored. Harnessing the patient's immune system to fight their cancer is an additional exciting route that is being considered. The "best" path to inhibiting KRAS has yet to be determined, with each having promise as well as potential pitfalls. We will summarize the state-of-the-art for each direction, focusing on efforts directed toward the development of therapeutics for pancreatic cancer patients with mutated KRAS.

OBJECTIVE: With the expanding indications for and increasing popularity of minimally invasive surgery (MIS) for lumbar spinal fusion, large-scale outcomes analysis to compare MIS approaches with open procedures is warranted. METHODS: The authors queried the Quality Outcomes Database for patients who underwent elective lumbar fusion for degenerative spine disease. They performed optimal matching, at a 1:2 ratio between patients who underwent MIS and those who underwent open lumbar fusion, to create two highly homogeneous groups in terms of 33 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, indications, and operative details). The outcomes of interest were overall satisfaction, decrease in Oswestry Disability Index (ODI), and back and leg pain, as well as hospital length of stay (LOS), operative time, reoperations, and incidental durotomy rate. Satisfaction was defined as a score of 1 or 2 on the North American Spine Society scale. Minimal clinically important difference (MCID) in ODI was defined as ≥ 30% decrease from baseline. Outcomes were assessed at the 3- and 12-month follow-up evaluations. RESULTS: After the groups were matched, the MIS and open groups consisted of 1483 and 2966 patients, respectively. Patients who underwent MIS fusion had higher odds of satisfaction at 3 months (OR 1.4, p = 0.004); no difference was demonstrated at 12 months (OR 1.04, p = 0.67). Lumbar stenosis, single-level fusion, higher American Society of Anesthesiologists Physical Status Classification System grade, and absence of spondylolisthesis were most prominently associated with higher odds of satisfaction with MIS compared with open surgery. Patients in the MIS group had slightly lower ODI scores at 3 months (mean difference 1.61, p = 0.006; MCID OR 1.14, p = 0.0495) and 12 months (mean difference 2.35, p < 0.001; MCID OR 1.29, p < 0.001). MIS was also associated with a greater decrease in leg and back pain at both follow-up time points. The two groups did not differ in operative time and incidental durotomy rate; however, LOS was shorter for the MIS group. Revision surgery at 12 months was less likely for patients who underwent MIS (4.1% vs 5.6%, p = 0.032). CONCLUSIONS: In patients who underwent lumbar fusion for degenerative spinal disease, MIS was associated with higher odds of satisfaction at 3 months postoperatively. No difference was demonstrated at the 12-month follow-up. MIS maintained a small, yet consistent, superiority in decreasing ODI and back and leg pain, and MIS was associated with a lower reoperation rate.

OBJECTIVE: The Quality Outcomes Database (QOD) was established in 2012 by the NeuroPoint Alliance, a nonprofit organization supported by the American Association of Neurological Surgeons. Currently, the QOD has launched six different modules to cover a broad spectrum of neurosurgical practice-namely lumbar spine surgery, cervical spine surgery, brain tumor, stereotactic radiosurgery (SRS), functional neurosurgery for Parkinson's disease, and cerebrovascular surgery. This investigation aims to summarize research efforts and evidence yielded through QOD research endeavors. METHODS: The authors identified all publications from January 1, 2012, to February 18, 2023, that were produced by using data collected prospectively in a QOD module without a prespecified research purpose in the context of quality surveillance and improvement. Citations were compiled and presented along with comprehensive documentation of the main study objective and take-home message. RESULTS: A total of 94 studies have been produced through QOD efforts during the past decade. QOD-derived literature has been predominantly dedicated to spinal surgical outcomes, with 59 and 22 studies focusing on lumbar and cervical spine surgery, respectively, and 6 studies focusing on both. More specifically, the QOD Study Group-a research collaborative between 16 high-enrolling sites-has yielded 24 studies on lumbar grade 1 spondylolisthesis and 13 studies on cervical spondylotic myelopathy, using two focused data sets with high data accuracy and long-term follow-up. The more recent neuro-oncological QOD efforts, i.e., the Tumor QOD and the SRS Quality Registry, have contributed 5 studies, providing insights into the real-world neuro-oncological practice and the role of patient-reported outcomes. CONCLUSIONS: Prospective quality registries are an important resource for observational research, yielding clinical evidence to guide decision-making across neurosurgical subspecialties. Future directions of the QOD efforts include the development of research efforts within the neuro-oncological registries and the American Spine Registry-which has now replaced the inactive spinal modules of the QOD-and the focused research on high-grade lumbar spondylolisthesis and cervical radiculopathy.