The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review.

BACKGROUND: Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival. METHODS: The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched. RESULTS: Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%). CONCLUSIONS: For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.

Surgical Management of Hook of Hamate Fractures: A Systematic Review of Outcomes.

Purpose: This review aimed to compare the postoperative outcomes of open reduction internal fixation (ORIF) versus excision in the surgical treatment of hook of hamate fractures. Methods: A systematic review of PubMed and EMBASE databases from 1954 to 2023 was performed using the search term "hook of hamate fracture" to identify all publications regarding the use of ORIF or excision in the treatment of hook of hamate fractures. Outcomes included a return to sport, pain, ulnar nerve dysfunction, flexor tendon dysfunction, union rate, wrist range of motion (ROM; % of contralateral hand), grip strength (% of contralateral hand), and quick disabilities of arm, shoulder, and hand scores. Results: Twenty-seven of the 705 total screened articles were included. Excision of the hook of hamate (n = 779) resulted in a shorter return to sport time (6 vs 7.8 weeks), lower rates of postoperative pain (6.1% vs 33.3%), higher rates of ulnar nerve sensory dysfunction (4.2% vs 0%), and higher rates of ulnar nerve motor dysfunction (1.5% vs 0%) relative to ORIF (n = 51). Chronic fractures had a longer return to sport time (7.2 vs 5.7 weeks) relative to nonchronic injuries. Conclusions: Both surgical procedures appear to yield acceptable outcomes in the treatment of hook of hamate fractures. However, based on the sparsity of available data, we are unable to determine a consistent difference between hook of hamate excision and ORIF. Clinical relevance: To our knowledge, no current consensus on the optimal surgical treatment for hook of hamate fractures exists. Our findings emphasize the need for a large prospective cohort study using standardized outcomes to provide strong evidence as to whether surgical excision or ORIF yields greater outcomes in the treatment of hook of hamate fractures.

Implementation of a New Surgeon Onboarding Program in an Academic-affiliated Community Hospital.

Best practices in onboarding are well-established, but surgeons frequently receive suboptimal introductions to new practice settings. At the same time, increasing regionalization of surgical programs and strategic alignments between academic and community hospitals have increased the demand for surgeons to practice at multiple sites with variable resources and institutional cultures. In response to this growing problem, we developed and implemented a surgeon onboarding program in an academic-affiliated community hospital. This pilot demonstrated excellent process adherence, user satisfaction, and significant improvements in preparedness to practice. We therefore conclude that robust onboarding is feasible and can be readily implemented by a local team to promote safe transitions in practice settings for surgeons.

Effectors Enabling Adaptation to Mitochondrial Complex I Loss in Hürthle Cell Carcinoma.

Oncocytic (Hürthle cell) carcinoma of the thyroid (HCC) is genetically characterized by complex I mitochondrial DNA mutations and widespread chromosomal losses. Here, we utilize RNA sequencing and metabolomics to identify candidate molecular effectors activated by these genetic drivers. We find glutathione biosynthesis, amino acid metabolism, mitochondrial unfolded protein response, and lipid peroxide scavenging to be increased in HCC. A CRISPR-Cas9 knockout screen in a new HCC model reveals which pathways are key for fitness, and highlights loss of GPX4, a defense against lipid peroxides and ferroptosis, as a strong liability. Rescuing complex I redox activity with the yeast NADH dehydrogenase (NDI1) in HCC cells diminishes ferroptosis sensitivity, while inhibiting complex I in normal thyroid cells augments ferroptosis induction. Our work demonstrates unmitigated lipid peroxide stress to be an HCC vulnerability that is mechanistically coupled to the genetic loss of mitochondrial complex I activity. SIGNIFICANCE: HCC harbors abundant mitochondria, mitochondrial DNA mutations, and chromosomal losses. Using a CRISPR-Cas9 screen inspired by transcriptomic and metabolomic profiling, we identify molecular effectors essential for cell fitness. We uncover lipid peroxide stress as a vulnerability coupled to mitochondrial complex I loss in HCC. See related article by Frank et al., p. 1884. This article is highlighted in the In This Issue feature, p. 1749.