Current management of succinate dehydrogenase-deficient gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are increasingly recognized as having diverse biology. With the development of tyrosine kinase inhibitors molecularly matched to oncogenic KIT and PDGFRA mutations, GISTs have become a quintessential model for precision oncology. However, about 5-10% of GIST lack these driver mutations and are deficient in succinate dehydrogenase (SDH), an enzyme that converts succinate to fumarate. SDH deficiency leads to accumulation of succinate, an oncometabolite that promotes tumorigenesis. SDH-deficient GISTs are clinically unique in that they generally affect younger patients and are associated with GIST-paraganglioma hereditary syndrome, also known as Carney-Stratakis Syndrome. SDH-deficient GISTs are generally resistant to tyrosine-kinase inhibitors, the standard treatment for advanced or metastatic GIST. Thus, surgical resection is the mainstay of treatment for localized disease, but recurrence is common. Clinical trials are currently underway investigating systemic agents for treatment of advanced SDH-deficient GIST. However, further studies are warranted to improve our understanding of SDH-deficient GIST disease biology, natural history, surgical approaches, and novel therapeutics.

The effect of hospital safety-net burden on outcomes, cost, and reportable quality metrics after emergent clipping and coiling of ruptured cerebral aneurysms.

OBJECTIVE: Safety-net hospitals deliver care to a substantial share of vulnerable patient populations and are disproportionately impacted by hospital payment reform policies. Complex elective procedures performed at safety-net facilities are associated with worse outcomes and higher costs. The effects of hospital safety-net burden on highly specialized, emergent, and resource-intensive conditions are poorly understood. The authors examined the effects of hospital safety-net burden on outcomes and costs after emergent neurosurgical intervention for ruptured cerebral aneurysms. METHODS: The authors conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) from 2002 to 2011. Patients ≥ 18 years old who underwent emergent surgical clipping and endovascular coiling for aneurysmal subarachnoid hemorrhage (SAH) were included. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital included in the NIS database. Hospitals that performed clipping and coiling were stratified as low-burden (LBH), medium-burden (MBH), and high-burden (HBH) hospitals. RESULTS: A total of 34,647 patients with ruptured cerebral aneurysms underwent clipping and 23,687 underwent coiling. Compared to LBHs, HBHs were more likely to treat black, Hispanic, Medicaid, and uninsured patients (p < 0.001). HBHs were also more likely to be associated with teaching hospitals (p < 0.001). No significant differences were observed among the burden groups in the severity of subarachnoid hemorrhage. After adjusting for patient demographics and hospital characteristics, treatment at an HBH did not predict in-hospital mortality, poor outcome, length of stay, costs, or likelihood of a hospital-acquired condition. CONCLUSIONS: Despite their financial burden, safety-net hospitals provide equitable care after surgical clipping and endovascular coiling for ruptured cerebral aneurysms and do not incur higher hospital costs. Safety-net hospitals may have the capacity to provide equitable surgical care for highly specialized emergent neurosurgical conditions.

Improving Door to Groin Puncture Time for Mechanical Thrombectomy via Iterative Quality Protocol Interventions.

INTRODUCTION: Delays in door to groin puncture time (DGPT) for patients with ischemic stroke caused by acute large vessel occlusions (LVO) are associated with worse clinical outcomes. We present the results of a quality improvement protocol for endovascular stroke treatment at the University of California, San Diego (UCSD) that aimed to minimize DGPT. MATERIALS AND METHODS: Our stroke team implemented a series of quality improvement measures to decrease DGPT, with a target of 90 minutes or less. Sixty-three patients treated at our center were retrospectively divided into three groups based on the date of their intervention as a proxy for the implementation of process improvement protocols: 23 patients treated from July to December 2015, 24 patients treated from January to July 2016, and 16 patients treated from July 2016 to December 2016. Multivariate log-linear and logistic regression analyses were used to assess the predictors of prolonged DGPT and compliance with target DGPT (<90 min), respectively. RESULTS: Date of intervention-a proxy for the implementation of process improvement protocols-was predictive of compliance with target DGPT. Patients treated from July 2016 to December 2016-after the full implementation of process improvements-were 3.2 times more likely to meet or exceed the target DGPT compared to patients treated from July 2015 to December 2015 (p=0.011). When adjusting for potential confounders in a multivariate analysis, patients in the final cohort were associated with shorter DGPT (Exp(B)=0.61, p=0.013) and remained significantly more likely to achieve the DGPT goal (OR=14.2, p=0.007). CONCLUSION: An iterative quality improvement process can significantly improve DGPT. This analysis demonstrates the utility of a formal quality improvement system at an academic comprehensive stroke center.

Corneal stromal elasticity and viscoelasticity assessed by atomic force microscopy after different cross linking protocols.

The purpose of this study was to evaluate elasticity and viscoelasticity in the anterior and deeper stromal regions of the cornea after cross linking with three different protocols using atomic force microscopy (AFM) through indentation. A total of 40 porcine corneas were used in this study and were divided into 4 groups (10 corneas per group): control (no treatment), Dresden (corneal epithelial debridement, riboflavin pretreatment for 30 min and a 3mw/cm(2) for 30 min UVA irradiation), accelerated (corneal epithelial debridement, riboflavin pretreatment for 30 min and a 30mw/cm(2) for 3 min UVA irradiation), and genipin (corneal epithelial debridement and submersion of anterior surface in a 1% genipin solution for 4 h). Elasticity and viscoelasticity were quantified using AFM through indentation for all corneas, for the anterior stroma and at a depth of 200 µm. For the control, Dresden, accelerated, and genipin groups, respectively, the average Young's modulus for the anterior stromal region was 0.60 ± 0.58 MPa, 1.58 ± 1.04 MPa, 0.86 ± 0.46 MPa, and 1.71 ± 0.51 MPa; the average for the 200 µm stromal depth was 0.08 ± 0.06 MPa, 0.08 ± 0.04 MPa, 0.08 ± 0.04 MPa, and 0.06 ± 0.01 MPa. Corneas crosslinked with the Dresden protocol and genipin were significantly stiffer than controls (p < 0.05) in the anterior region only. For the control, Dresden, Accelerated, and genipin groups, respectively, the average calculated apparent viscosity for the anterior stroma was 88.2 ± 43.7 kPa-s, 8.3 ± 7.1 kPa-s, 8.1 ± 2.3 kPa-s, and 9.5 ± 3.8 kPa-s; the average for the 200 µm stromal depth was 35.0 ± 3.7 kPa-s, 49.6 ± 35.1 kPa-s, 42.4 ± 17.6 kPa-s, and 41.8 ± 37.6 kPa-s. All crosslinking protocols resulted in a decrease in viscosity in the anterior region only (p < 0.05). The effects of cross-linking seem to be limited to the anterior corneal stroma and do not extend to the deeper stromal region. Additionally, the Dresden and genipin protocols seem to produce a stiffer anterior corneal stroma when compared to the accelerated protocol.