Faculty Bibliography

BACKGROUND/UNASSIGNED:Hallux varus is an uncommon pathology with no consensus regarding outcomes following the various surgical techniques available for its management. The purpose of this systematic review was to evaluate clinical outcomes, radiographic parameters, and complications following surgical management of hallux varus. METHODS/UNASSIGNED:During August 2025, the PubMed, Embase, and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following surgical management of hallux varus. RESULTS/UNASSIGNED:Eleven studies comprising 152 patients (159 feet) were included. Among patients treated with soft-tissue procedures, the weighted mean age was 53.5 ± 5.1 years with a weighted mean follow-up time of 35.3 ± 11.1 months. The weighted mean American Orthopedic Foot and Ankle Society (AOFAS) score improved 25.6 points, with corresponding improvements in hallux valgus angle (HVA) of 17.5°. The complication and failure rates were 18.9% and 11.3%, respectively. In the osteotomy cohort, the weighted mean age was 52.4 ± 6.0 years and the weighted mean follow-up time was 44.3 ± 15.6 months. The weighted mean AOFAS score improved 23.7 points, with improvements in of 24.5°. The complication and failure rates were 1.7% and 3.3%, respectively. In the arthrodesis cohort, the weighted mean age was 63.3 ± 0.7 years and the weighted mean follow-up time was 44.2 ± 30.1 months. The mean AOFAS improved 51 points, with improvements in HVA of 25.2°. The overall complication and failure rates were 10.7% and 3.6%, respectively. CONCLUSIONS/UNASSIGNED:Surgical management of hallux varus is associated with meaningful improvements in clinical outcomes and radiographic alignment across a range of operative techniques. No technique could be definitively identified as superior given the absence of comparative studies and variability in reported outcomes. Future studies should prioritize prospective, comparative designs with standardized outcome measures and long-term follow-up to better establish optimal management strategies for hallux varus. REGISTRATION/UNASSIGNED:CRD420261280842 (Prospero identifier). LEVEL OF EVIDENCE/UNASSIGNED:IV, systematic review.

Sports cardiology has emerged as a critical subspecialty within cardiovascular medicine, focusing on the prevention, diagnosis, and management of cardiovascular conditions in athletes and physically active individuals. As participation in both competitive and recreational sports continues to grow globally, physicians increasingly encounter physiologic adaptations to exercise that may mimic pathology. Cardiac magnetic resonance (CMR) has emerged as a cornerstone in the evaluation of athletes with suspected or diagnosed cardiovascular disease. Its ability to provide comprehensive tissue characterization, functional and morphologic assessment makes it uniquely suited for distinguishing physiologic cardiac remodeling from pathologic conditions.

UNLABELLED:LKB1 mutations in lung cancer promote an immunosuppressive tumor microenvironment, but the underlying mechanisms remain unknown. Using genetically engineered mouse models and human tumor samples, we demonstrate that LKB1 loss leads to high expression of the cytokine leukemia-inhibitory factor (LIF), which through a cancer cell-autonomous autocrine loop, orchestrates the infiltration of immunosuppressive SiglecFHi neutrophils and Arg1+ interstitial macrophages. Genetic deletion of Lifr, the receptor for LIF, on Lkb1-mutant lung tumors revealed that autocrine LIF signaling induces tumor plasticity and the emergence of a Sox17+ dedifferentiated inflammatory cell state. Antibody-mediated LIF neutralization selectively eliminates the Sox17+ tumor cell state, reduces immunosuppressive myeloid cells, and enhances antitumor T-cell responses. Our study uncovers a novel LKB1-LIF axis driving immune evasion and identifies LIF as a potential therapeutic target in LKB1-mutant lung cancer. This work highlights the interplay between tumor genetics, cellular plasticity, and immune regulation in lung cancer progression. SIGNIFICANCE/UNASSIGNED:LKB1-mutant lung cancers express LIF, which induces an immunosuppressive Sox17+ tumor state. Anti-LIF therapy eliminates this state and restores antitumor immunity, revealing a novel vulnerability in this aggressive cancer subtype lacking effective targeted therapies.

Breast cancer remains the second leading cause of cancer-related mortality among women, with triple-negative breast cancer (TNBC) exhibiting a particularly poor five-year prognosis. Here, we demonstrated that, among genetic and pharmacological perturbations targeting DNA replication, suppression of DNA polymerase epsilon (POLE) induced a potent, TNBC-specific gene expression signature enriched in inflammatory cytokines that are transcriptional targets of NF-κB. TNBC cells exhibited markedly higher levels of DNA damage and canonical NF-κB activation compared to luminal breast cancer cells. Notably, NF-κB activation in this context depended on the canonical component RELA but not the non-canonical component RELB. Mechanistically, ATM, STING, and RIG-I each contributed to NF-κB activation following POLE suppression. POLE suppression in an in vivo murine TNBC model led to cancer cell-intrinsic elimination of tumor burden and increased immune cell infiltration. Together, these findings support a model in which replication stress from POLE inhibition triggers robust NF-κB-mediated inflammation and immune microenvironment remodeling in TNBC and can independently trigger tumor eradication. These results suggest a potential therapeutic avenue for targeting POLE in TNBC.

Advances in targeted therapies, immunotherapy, and early detection have revolutionized lung cancer treatment and extended survival. Nonetheless, lung cancer remains highly fatal. Here, we identify knowledge gaps and propose critical areas of future research, aligning with the mission of the AACR Lung Cancer Task Force. We delineate research priorities, including advancing prevention initiatives, enhancing early detection strategies, developing novel treatments, and refining patient stratification. Addressing disparities and increasing efforts on relatively neglected lung cancer subtypes are also essential. Finally, international collaboration, centralized clinical trial databases, novel clinical trial designs, and artificial intelligence-driven analytics should accelerate precision medicine and aid in elucidating drug resistance mechanisms. Together, these efforts promise to improve patient outcomes.

BACKGROUND:Postoperative improvement in patient-reported outcomes is a key measure of total hip arthroplasty success. The Minimum Clinically Important Difference (MCID) represents the smallest improvement perceived as beneficial. Distribution-based MCIDs have been criticized for producing thresholds smaller than anchor-based values, questioning their clinical relevance. We hypothesized they may capture early biological recovery signals associated with subsequent patient-reported outcomes and aimed to determine whether failure to achieve an early distribution-based MCID (seven to 31 days) was associated with failure to achieve a late anchor-based MCID (90 to 365 days). METHODS:This retrospective cohort study included patients undergoing primary unilateral total hip arthroplasty for osteoarthritis from January 1, 2021, to January 1, 2025, comprising 844 patients. Patients were included if they completed 'Hip disability and Osteoarthritis Outcome Score, Joint Replacement' questionnaires preoperatively, at seven to 31 days, and at 90 to 365 days. Distribution-based MCID was defined as a ≥ 7.8-point improvement, and anchor-based MCID as ≥ 23 points. Multivariable regression assessed associations between early distribution-based and late anchor-based MCID failure, adjusting for demographics and clinical factors. RESULTS:In the early period (seven to 31 days), 565 patients (67.0%) achieved the distribution-based MCID, whereas 573 (67.9%) achieved the late anchor-based MCID (90 to 365 days). Among patients who failed to attain an early distribution-based MCID, 54.1% (151 of 279) also failed the late anchor-based MCID, compared with 21.2% (120 of 565) among early achievers (P < 0.001). Early distribution-based MCID failure was a strong independent predictor of late anchor-based MCID failure (odds ratio: 2.61; 95% confidence interval: 1.85 to 3.68; P < 0.001). Higher baseline Hip disability and Osteoarthritis Outcome Score, Joint Replacement scores and facility-based discharge were also independently associated with late failure (P < 0.05). CONCLUSIONS:Failure to achieve an early distribution-based MCID is strongly associated with poor patient-reported outcomes up to one year. Early distribution-based MCID attainment may represent an important prognostic marker, enabling timely clinical intervention.