Evaluation of Post-Operative Outcomes of Femoral Neck Fracture Interventions: A Systematic Review.

Introduction: Femoral neck fractures (FNF) represent a significant challenge in orthopedic practice, demanding prompt intervention to restore function and mobility in affected individuals. Numerous surgical interventions have been developed to address these fractures, including internal fixation with devices such as the Femoral Neck System (FNS, DePuy Synthes, Inc., West Chester, PA, USA).

SOS1 Inhibition Enhances the Efficacy of KRASG12C Inhibitors and Delays Resistance in Lung Adenocarcinoma.

The clinical effectiveness of KRASG12C inhibitors (G12Ci) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. Here, we identified targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 as a strategy to improve responses to G12Ci treatment. SOS1i enhanced the efficacy of G12Ci and limited rebound RTK/ERK signaling to overcome intrinsic/adaptive resistance, but this effect was modulated by SOS2 protein levels.

Comparison of Balloon Guide Catheters and Standard Guide Catheters for Acute Ischemic Stroke: An Updated Systematic Review and Meta-analysis.

Objective: The objective of this study was to update our 2021 systematic review and meta-analysis which reported that balloon guide catheters (BGC) are associated with superior clinical and angiographic outcomes compared to standard guide catheters for treatment of acute ischemic stroke.

Methods: We conducted a systematic review of 7 electronic databases to identify literature published between January 2010 and September 2023 reporting BGC versus non-BGC approaches. Primary outcomes were final modified thrombolysis in cerebral infarction (mTICI) ≥2b, first-pass effect (mTICI ≥2c on first pass), and modified Rankin scale 0-2 at 90 days.

SOS1 inhibition enhances the efficacy of and delays resistance to G12C inhibitors in lung adenocarcinoma.

Clinical effectiveness of KRAS G12C inhibitors (G12Cis) is limited both by intrinsic and acquired resistance, necessitating the development of combination approaches. We found that targeting proximal receptor tyrosine kinase (RTK) signaling using the SOS1 inhibitor (SOS1i) BI-3406 both enhanced the potency of and delayed resistance to G12Ci treatment, but the extent of SOS1i effectiveness was modulated by both SOS2 expression and the specific mutational landscape. SOS1i enhanced the efficacy of G12Ci and limited rebound RTK/ERK signaling to overcome intrinsic/adaptive resistance, but this effect was modulated by SOS2 protein levels.

The efficacy of prophylactic vertebroplasty for preventing proximal junctional complications after spinal fusion: a systematic review.

Background Context: Prophylactic vertebroplasty (VP) is performed at the upper level of instrumentation during spinal fusion to reduce the risk of proximal junctional kyphosis (PJK), proximal junctional fracture (PJFx), and proximal junctional failure (PJF). This study investigated the effect of VP on patient outcomes after spinal fusion.

Purpose: The aim of this systematic review was to evaluate the effect of prophylactic VP on the incidence of PJK in patients with spinal fusion.

Patient outcomes after treatment of brain aneurysm in small diameter vessels with the silk vista baby flow diverter: A systematic review.

Background: The Silk Vista Baby (SVB, BALT) is a first-in-class flow-diverter device delivered using a 0.017" microcatheter, designed for the treatment of intracranial aneurysms, including those in small diameter vessels. This study reports a systematic literature review (SLR) to evaluate the safety and efficacy of using SVB to treat intracranial aneurysms in vessels less than 3.

The effect of instrumentation staging on patient outcomes in pyogenic vertebral osteomyelitis: A systematic review.

Background: Pyogenic vertebral osteomyelitis is a bacterial infection of the vertebral body that is often treatable with antibiotics, but some cases require additional surgical debridement of the infected tissue. Instrumentation is often utilized for stabilization of the spine as part of the surgical treatment, but controversy remains over the relative risks and benefits of acute instrumentation performed simultaneously with debridement versus delayed instrumentation performed days or weeks after debridement. The purpose of this review was to investigate the relative effects of acute and delayed instrumentation in treatment for pyogenic vertebral osteomyelitis on patient outcomes.

Efficacy of antiviral therapies for COVID-19: a systematic review of randomized controlled trials.

Background: Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment.

Methods: A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment.

Peripheral Nerve Blocks Outperform General Anesthesia for Pain Control in Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-analysis.

Purpose: The purpose of this review is to compare the effectiveness of different peripheral nerve blocks and general anesthesia (GA) in controlling postoperative pain after arthroscopic rotator cuff repair (ARCR).

Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted for the period of January 1, 2005, to February 16, 2021, by searching the following databases: PubMed, Cochrane, Embase, and Arthroscopyjournal.org.

Breaking Oncogene Addiction: Getting RTK/RAS-Mutated Cancers off the SOS.

In RTK/RAS-mutated cancers, therapeutic resistance is driven by rebound activation of multiple RTKs; broad inhibition of RTK signaling can potentially delay therapeutic resistance for a majority of patients. A new SOS1 inhibitor, BI-3406, broadly inhibits proximal RTK signaling will greatly expand the efficacy of therapies used to treat RTK/RAS-mutated cancers.

The Role of Wild-Type RAS in Oncogenic RAS Transformation.

The family of oncogenes (, , and ) are among the most frequently mutated protein families in cancers. -mutated tumors were originally thought to proliferate independently of upstream signaling inputs, but we now know that non-mutated wild-type (WT) RAS proteins play an important role in modulating downstream effector signaling and driving therapeutic resistance in -mutated cancers. This modulation is complex as different WT RAS family members have opposing functions.

Marked synergy by vertical inhibition of EGFR signaling in NSCLC spheroids shows SOS1 is a therapeutic target in EGFR-mutated cancer.

Drug treatment of 3D cancer spheroids more accurately reflects in vivo therapeutic responses compared to adherent culture studies. In EGFR-mutated lung adenocarcinoma, EGFR-TKIs show enhanced efficacy in spheroid cultures. Simultaneous inhibition of multiple parallel RTKs further enhances EGFR-TKI effectiveness.

Distinct Binding Preferences between Ras and Raf Family Members and the Impact on Oncogenic Ras Signaling.

The Ras GTPases are frequently mutated in human cancer, and, although the Raf kinases are essential effectors of Ras signaling, the tumorigenic properties of specific Ras-Raf complexes are not well characterized. Here, we examine the ability of individual Ras and Raf proteins to interact in live cells using bioluminescence resonance energy transfer (BRET) technology. We find that C-Raf binds all mutant Ras proteins with high affinity, whereas B-Raf exhibits a striking preference for mutant K-Ras.

Anchorage-independent growth conditions reveal a differential SOS2 dependence for transformation and survival in -mutant cancer cells.

The RAS family of genes (, and ) is mutated in around 30% of human tumours. Wild-type RAS isoforms play an important role in mutant RAS-driven oncogenesis, indicating that RasGEFs may play a significant role in mutant RAS-driven transformation. We recently reported a hierarchical requirement for SOS2 in mutant RAS-driven transformation in mouse embryonic fibroblasts, with KRAS>NRAS>HRAS (Sheffels et al.

Oncogenic RAS isoforms show a hierarchical requirement for the guanine nucleotide exchange factor SOS2 to mediate cell transformation.

About a third of tumors have activating mutations in , , or , genes encoding guanosine triphosphatases (GTPases) of the RAS family. In these tumors, wild-type RAS cooperates with mutant RAS to promote downstream effector activation and cell proliferation and transformation, suggesting that upstream activators of wild-type RAS are important modulators of mutant RAS-driven oncogenesis. The guanine nucleotide exchange factor (GEF) SOS1 mediates KRAS-driven proliferation, but little is understood about the role of SOS2.