Faculty Bibliography

The rate of recurrent instability following primary medial patellofemoral ligament (MPFL) reconstruction has been reported to be as high as 6.7%. However, limited studies have reported on clinical outcomes and complications following revision MPFL reconstruction. Furthermore, the role of previously identified risk factors for primary failure (e.g., patella alta and trochlear dysplasia) warrants further study in this patient population. Therefore, the goal of this study was 2-fold. First, to evaluate the prevalence of anatomic risk factors and technical errors among patients presenting for revision patellofemoral surgery. Second, to report early clinical outcomes following revision MPFL reconstruction. A single-surgeon registry was queried for patients who underwent revision MPFL reconstruction (including prior MPFL imbrication, MPFL reconstruction, tibial tubercle osteotomy [TTO]) from November 2015 to June 2022. Preoperative imaging was evaluated for risk factors including (1) misplacement of the femoral tunnel, (2) Caton-Deschamps index, (3) tibial tubercle-trochlear groove distance (TT-TG), (4) patellar tilt, and (5) trochlear dysplasia. Patient-reported outcomes and complications were obtained at final follow-up (minimum 1 year). The study included 32 patients (72% female, age: 23.9 ± 6.6 years). Mean time from index surgery to revision MPFL reconstruction was 4.8 ± 4.7 years (range 0.6 to 17.9 years). The most prevalent anatomic risk factors were patella alta (72%), TT-TG >15 mm (53%), trochlear dysplasia (Dejour type B, C, or D) (50%), and excessive patellar tilt (41%). The median number of risk factors was 3 (range 0-6), and 17 patients (53%) had three or more risk factors. At final follow-up (24.1 ± 14.5 months), no patients experienced recurrent patellofemoral instability or graft failure. Postoperative IKDC (p < 0.001) and SF-12 PCS (p < 0.001) scores improved significantly compared with preoperatively. In conclusion, the majority of patients presenting for revision MPFL reconstruction had three or more risk factors for recurrent dislocation.IV, Case Series.

PURPOSE/UNASSIGNED:To determine clinical outcome changes and wear compliance rates associated with the use of a custom-fit anterior knee unloader brace in a prospective cohort of patients with clinical symptoms derived from patellofemoral osteoarthritis (PFOA). METHODS/UNASSIGNED:Adults ≥ 18 years with PFOA or multicompartment OA with patellofemoral involvement were enrolled in this study. Participants received a custom-fit Icarus Ascender OA Brace with instructions to wear it during daily activity for 4 weeks. Patient-reported outcomes (PROs) were collected at the pre- and postbracing intervals. PROs were compared from pre- to postbracing time points. Improvement from moderate or severe symptoms prebracing to mild or no symptoms postbracing was analyzed. RESULTS/UNASSIGNED: < .001). 66.42% of knees exceeded minimum clinically important difference (MCID) for KOOS JR. MCID achievement was higher in patients reporting "moderate or worse" stiffness (75.24%), pain (77.66%), and functional limitation (78.72%) baseline KOOS JR subscores compared with those reporting "mild or no" stiffness (39.39%), pain (40.00%), and functional limitation (37.50%). Sixty-two of 71 (87.32%) patients reported "moderate or worse" symptoms for stiffness, pain, and ADL subscores. CONCLUSIONS/UNASSIGNED:Prescription of an anterior knee unloader brace in patients with PFOA or multicompartmental knee OA with patellofemoral involvement results in moderate compliance and improvement in pain and clinical function in the majority of patients at short-term follow-up. LEVEL OF EVIDENCE/UNASSIGNED:Level IV, therapeutic retrospective case series.

RTEL1 R1264H is a founder variant with a carrier frequency of 0.3%-1.0% in the Ashkenazi Jewish population. While biallelic RTEL1 R1264H causes a severe form of telomere biology disorder (TBD) presenting in childhood, the clinical significance of monoallelic carrier status has remained uncertain, limiting effective counseling and management. Here, we describe the clinical features, telomere lengths, and tumor somatic profiles of cancer patients found to be heterozygous for RTEL1 R1264H to evaluate for evidence of subclinical TBD in this population. Among 39,337 individuals who underwent RTEL1 germline analysis via MSK-IMPACT, 32 (0.08%) were incidentally found to be heterozygous for RTEL1 R1264H. Three individuals (9%) met diagnostic criteria for TBD based on compatible clinical features and telomere shortening, and two additional individuals (6%) had histories suspicious for TBD but did not have telomere length data available. Notably, 7 individuals (22%) experienced severe or fatal therapy-related toxicities, despite many lacking other clinical features of a TBD. These findings support that RTEL1 R1264H can act in an autosomal dominant fashion and confer TBD disease risk, albeit with low penetrance, and may increase susceptibility to treatment-related complications.

In contrast to living organisms, viruses were long thought to lack protein synthesis machinery and instead depend on host factors to translate viral transcripts. Here, we discover that giant DNA viruses encode a distinct and functional IF4F translation-initiation complex to drive protein synthesis, thereby blurring the line between cellular and acellular biology. During infection, eukaryotic IF4F on host ribosomes is replaced by an essential viral IF4F that regulates viral translation, virion formation, and replication plasticity during altered host states. Structural dissection of viral IF4F reveals that the mRNA cap-binding subunit mediates exclusive interactions with viral mRNAs, constituting a molecular switch from translating host to viral proteins. Thus, our study establishes that viruses express a eukaryotic translation-initiation complex for protein synthesis, illuminating a series of evolutionary innovations in a core process of life.

Tumor-infiltrating T cells have been the primary focus of cancer immunotherapy; however, accumulating evidence points to a critical role for B cells and plasma cells in shaping responses to immune checkpoint blockade. In this study, we investigated the humoral immune response in 38 patients with hepatocellular carcinoma treated with neoadjuvant anti-programmed cell death protein 1 (PD-1) therapy. In responders, defined by more than 50% tumor necrosis, we observed on-treatment enrichment of clonally expanded IgG1⁺ plasma cells within the tumor. Clonal tracking revealed that anti-PD-1 treatment expanded preexisting B cell clones associated with favorable clinical outcomes. Moreover, serum from responders contained IgG1 antibodies specific to cancer/testis antigens, including NY-ESO-1, and these humoral responses were linked to tumor-reactive T cell activity. We independently validated these findings across seven additional cohorts, encompassing single-cell and bulk sequencing data from 500 patients, spatial transcriptomics from seven patients and survival analyses from 1,582 patients. Our findings apply to recently approved treatments, such as PD-1 and vascular endothelial growth factor A (VEGF-A) blockade, but not to chemotherapy alone, suggesting broad relevance to individuals treated with immunotherapy. Collectively, our results demonstrate that PD-1 blockade induces tumor-specific IgG1⁺ plasma cell responses that complement cellular immunity and contribute to clinical benefit, underscoring a coordinated humoral-cellular axis in effective antitumor immunity.

BACKGROUND:Curative-intent pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) carries high rates of morbidity and recurrence. Patients with operable PDAC face a complex decision of whether to pursue resection. Factors impacting the decision-making process and decisional regret (DR) are relatively unexplored. PATIENTS AND METHODS/METHODS:Patients with PDAC who underwent curative-intent pancreatectomy at least 6 months prior to study recruitment completed validated surveys assessing DR, health literacy, shared decision-making, and quality of life. RESULTS:Overall, 60 patients (48% female) completed all surveys. Postoperative DR (DRS > 1) was reported in 21 (35%) patients. The median time from surgery to survey completion was 55 months in the DR Present group and 33 months in the DR Absent group (P = 0.895). Receipt of systemic therapy, operative characteristics, and postoperative course were similar between groups. The DR Present group had lower rates of obtaining advanced educational degrees (48% versus 76%, P = 0.031), lower health literacy (BRIEF score 14.8 ± 4.2 versus 17.0 ± 2.5, P = 0.014), and greater discordance between preferred and actual roles in the decision making process (Cohen's kappa 0.672 [95% CI 0.530-0.814] versus 0.912 [95% CI 0.852-0.972], P < 0.001). The DR Present group reported worse physical ability (EORTC score 77.8 ± 21.8 versus 91.3 ± 11.8, P = 0.014), functional role (EORTC score 63.5 ± 33.2 versus 85.5 ± 27.6, P = 0.008), and social activity (EORTC score 65.9 ± 35.9 versus 85.9 ± 21.4, P = 0.026) scores. CONCLUSIONS:Lower health literacy and discordance in preferred and actual decision-making roles negatively impacts post-pancreatectomy DR. Adequate preoperative counseling on potential quality of life changes is critical for informed decision-making.