All-Onlay Anterolateral Ligament Reconstruction Technique of the Knee.

The anterolateral ligament has gained attention as a secondary stabilizer of anterolateral rotatory stability of the knee. This has had implications among sports medicine specialists as an adjunct procedure with anterior cruciate ligament reconstruction to improve stability. As indications have evolved for its use as an anterior cruciate ligament reconstruction augment, so have the techniques for reconstruction. As such, we present a simple, efficient, and reproducible technique for all-onlay reconstruction with low-profile instrumentation that mitigates concerns for tunnel convergence.

Proceedings of the 1st biannual bridging the gaps in lung cancer conference.

Lung cancer is the leading cause of cancer death in the US and globally. The mortality from lung cancer has been declining, due to a reduction in incidence and advances in treatment. Although recent success in developing targeted and immunotherapies for lung cancer has benefitted patients, it has also expanded the complexity of potential treatment options for health care providers. To aid in reducing such complexity, experts in oncology convened a conference (Bridging the Gaps in Lung Cancer) to identify current knowledge gaps and controversies in the diagnosis, treatment, and outcomes of various lung cancer scenarios, as described here. Such scenarios relate to biomarkers and testing in lung cancer, small cell lung cancer, EGFR mutations and targeted therapy in non-small cell lung cancer (NSCLC), early-stage NSCLC, KRAS/BRAF/MET and other genomic alterations in NSCLC, and immunotherapy in advanced NSCLC.

A Finite Element Analysis Model for Magnetomotive Ultrasound Elastometry Magnet Design with Experimental Validation.

Objective: Magnetomotive ultrasound (MMUS) using magnetic nanoparticle contrast agents has shown promise for thrombosis imaging and quantitative elastometry via magnetomotive resonant acoustic spectroscopy (MRAS). Young's modulus measurements of smaller, stiffer thrombi require an MRAS system capable of generating forces at higher temporal frequencies. Solenoids with fewer turns, and thus less inductance, could improve high frequency performance, but the reduced force may compromise results. In this work, a computational model capable of predicting improved MRAS magnet configurations optimized for elastometry is presented and validated. Approach: Finite element analysis (FEA) was used to model the force and inductance of MRAS systems. The simulations incorporated both solenoid electromagnets and permanent magnets in three-dimensional steady-state, frequency domain, and time domain studies. Main results: The model successfully predicted a configuration in which permanent magnets could be used to increase the force supplied by an existing MRAS system. Accordingly, the displacement measured in a magnetically labeled validation phantom increased by a factor of 2.2 ± 0.3 when the force was predicted to increase by a factor of 2.2 ± 0.2. The model additionally identified a new solenoid configuration consisting of four smaller coils capable of providing sufficient force at higher driving frequencies. Significance: These results indicate two methods by which MRAS systems could be designed to deliver higher frequency magnetic forces without the need for experimental trial and error. Either the number of turns within each solenoid could be reduced while permanent magnets are added at precise locations, or a larger number of smaller solenoids could be used. These findings overcome a key challenge toward the goal of thrombosis elastometry via MMUS.

First-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations.

Introduction: Up to 20% of EGFR-mutated NSCLC cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. Methods: Patients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). Results: Thirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10-15), 22 months (95% CI: 17-32) and 36 months (95% CI, 29-48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10-15), median TTD was 19 months (95% CI: 17-38), and median OS was 48 months (95% CI: 25-not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5-22), median TTD of 26 months (95% CI: 5-36), and median OS of 36 months (95% CI: 20-46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression. Conclusions: Osimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient.

Antibody-drug conjugates in advanced lung cancer: Is this a new frontier?

Over the past decade, the lung cancer landscape has been dominated by targeted and immunotherapeutic approaches that have drastically shifted treatment paradigms for patients with advanced non-small cell lung cancer (NSCLC). Despite these scientific and clinical advances, there are still many unmet needs underscoring the importance of novel strategies. Antibody-drug conjugates (ADCs) represent one such strategy that is beginning to alter the therapeutic strategies for patients with advanced NSCLC. The rationale of ADCs is simple: selectively deliver cytotoxic payloads through an antibody-mediated process to target antigens expressed by cancer cells, sparing normal tissue and inflicting damage to tumors. Although this concept has been the leading view, preclinical and clinical observations are demonstrating that only a nascent mechanistic understanding of these agents exists. In this review, we discuss the underlying biology of ADCs and their structure and potential mechanisms of action, examine approved and promising ADC targets in lung cancer, and review emerging ADC targets and combinatorial strategies. Importantly, we address the unanswered questions surrounding ADCs in lung cancer, including biomarker selection, treatment sequencing, and mechanisms of resistance, as well as management of unique ADC-associated toxicities.

Perioperative Immunotherapy for Non-Small Cell Lung Cancer: Practical Application of Emerging Data and New Challenges.

Immune checkpoint inhibition, with or without chemotherapy, is an established standard of care for metastatic non-small cell lung cancer (NSCLC). For locally advanced NSCLC treated with chemoradiotherapy, consolidation immunotherapy has dramatically improved outcomes. Recently, immunotherapy has also been established as a valuable component of treatment for resectable NSCLC with pembrolizumab, atezolizumab, and nivolumab all approved for use in this setting. As more results read out from ongoing perioperative clinical trials, navigating treatment options will likely become increasingly complex for the practicing oncologist. In this paper, we distill key outcomes from major perioperative trials and highlight current knowledge gaps. In addition, we provide practical considerations for incorporating perioperative immunotherapy into the clinical management of operable NSCLC.

Psoralen: a narrative review of current and future therapeutic uses.

Psoralen is a family of naturally occurring photoactive compounds found in plants that acquire potential cytotoxicity when activated by specific frequencies of electromagnetic waves. Psoralens penetrate the phospholipid cellular membranes and insert themselves between the pyrimidines of deoxyribonucleic acid (DNA). Psoralens are initially biologically inert and acquire photoreactivity when exposed to certain classes of electromagnetic radiation, such as ultraviolet light. Once activated, psoralens form mono- and di-adducts with DNA, leading to marked cell apoptosis. This apoptotic effect is more pronounced in tumor cells due to their high rate of cell division. Moreover, photoactivated psoralen can inhibit tyrosine kinase signaling and influence the immunogenic properties of cells. Thus, the cytotoxicity of photoactivated psoralen holds promising clinical applications from its immunogenic properties to potential anti-cancer treatments. This narrative review aims to provide an overview of the current understanding and research on psoralen and to explore its potential future pharmacotherapeutic benefits in specific diseases.

Impact of Tumor-intrinsic Molecular Features on Survival and Acquired Tyrosine Kinase Inhibitor Resistance in ALK-positive NSCLC.

While tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in anaplastic lymphoma kinase (ALK) fusion-positive advanced non-small cell lung cancer (NSCLC), clinical outcomes vary and acquired resistance remains a significant challenge. We conducted a retrospective study of patients with ALK-positive NSCLC who had clinico-genomic data independently collected from two academic institutions (n = 309). This was paired with a large-scale genomic cohort of patients with ALK-positive NSCLC who underwent liquid biopsies (n = 1,118). Somatic co-mutations in TP53 and loss-of-function alterations in CDKN2A/B were most commonly identified (24.1% and 22.5%, respectively in the clinical cohort), each of which was independently associated with inferior overall survival (HR: 2.58; 95% confidence interval, CI: 1.62-4.09 and HR: 1.93; 95% CI: 1.17-3.17, respectively). Tumors harboring EML4-ALK variant 3 (v3) were not associated with specific co-alterations but were more likely to develop ALK resistance mutations, particularly G1202R and I1171N (OR: 4.11; P < 0.001 and OR: 2.94; P = 0.026, respectively), and had inferior progression-free survival on first-line TKI (HR: 1.52; 95% CI: 1.03-2.25). Non-v3 tumors were associated with L1196M resistance mutation (OR: 4.63; P < 0.001). EML4-ALK v3 and somatic co-alterations in TP53 and CDKN2A/B are associated with inferior clinical outcomes. v3 status is also associated with specific patterns of clinically important ALK resistance mutations. These tumor-intrinsic features may inform rational selection and optimization of first-line and consolidative therapy. SIGNIFICANCE: In a large-scale, contemporary cohort of patients with advanced ALK-positive NSCLC, we evaluated molecular characteristics and their impact on acquired resistance mutations and clinical outcomes. Our findings that certain ALK variants and co-mutations are associated with differential survival and specific TKI-relevant resistance patterns highlight potential molecular underpinnings of the heterogenous response to ALK TKIs and nominate biomarkers that may inform patient selection for first-line and consolidative therapies.

Examining the Relationship Between Value and Patient Satisfaction With Treatment in Total Joint Arthroplasty.

Background: A shift toward performance, cost, outcomes, and patient satisfaction has occurred with healthcare reform promoting value-based programs. The purpose of this study was to evaluate the relationship between patient satisfaction and value with treatment in a cohort of patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). Methods: Value was determined by the relationship of treatment outcome with episodic cost. Measurements included both clinical outcomes and patient-reported outcomes. Participating surgeons took part in the modified Delphi method resulting in an algorithm measuring patient value. Treatment outcome, cost, and resultant value (outcome/cost) of both TKA and THA were evaluated using binomial logistic regression by adjusting for age, gender, body mass index, Charlson comorbidity index, tobacco, education, and income with patient-reported satisfaction as the outcome. Results: This study had a total of 909 patients (TKA n = 438; THA n = 471), with an average age of 67 (TKA) and 65 (THA) years. Patient satisfaction shared a significant positive relationship with treatment outcome for TKA (odds ratio [OR] = 1.53, confidence interval [CI] = 1.35-1.73, P < .001) and THA (OR = 1.93, CI = 1.62-2.29, P < .001). Higher value was associated with a significantly higher odds of patient satisfaction for both TKA (OR = 1.39, CI = 1.25-1.54, P < .001) and THA (OR = 1.70, CI = 1.47-1.97, P < .001). Conclusions: This study showed a positive relationship between treatment outcome but not cost with subsequent value and patient satisfaction. This method provides a promising approach to comprehensively evaluate outcomes, cost, and value of total joint arthroplasty procedures. This approach can help predict the probability of value-driven patient satisfaction.

Characterizing the Native Microbiome Using Next-Generation Sequencing of Bilateral 'Aseptic' Knees.

BACKGROUND: Next generation sequencing (NGS) has proven ability to identify organisms beyond those identified through traditional culture-based techniques in cases of suspected prosthetic joint infection. However, there is concern that some microorganisms identified may represent the natural joint microbiome rather than pathogenic agents. This work sought to evaluate the presence of microorganisms identified with NGS in bilateral native, presumed "aseptic" knees with osteoarthritis. METHODS: There were 40 patients undergoing primary unilateral (30) or bilateral (10) total knee arthroplasty enrolled prospectively. During surgery, samples of fluid and tissue were obtained from operative knees, and joint fluid was obtained from nonoperative knees. Samples were sent for NGS analysis and processed according to manufacturer protocols. Patient age, body mass index, comorbidities, prior history of injections, and grade of arthritis were evaluated for association with positive NGS results. RESULTS: There were 3 of 80 samples (3.8%) that demonstrated positive NGS. There were two of these that had multiple microorganisms identified (1 knee with 4 microorganisms; 1 knee with 2 microorganisms). An additional 2 samples had positive NGS results below the manufacturer's threshold for reporting. The most common organism identified was Cutibacterium acnes, present in 2 of the 3 positive samples. No patient baseline characteristics were associated with positive NGS results. CONCLUSIONS: Some native knee joints with osteoarthritis have positive microorganisms identified with NGS. The presence of microorganisms in the native knee has important implications for better understanding the native joint microbiome as well as utilization of NGS in cases of suspected prosthetic joint infection.

Elucidating the Heterogeneity of Immunotherapy Response and Immune-Related Toxicities by Longitudinal ctDNA and Immune Cell Compartment Tracking in Lung Cancer.

PURPOSE: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect-especially in the setting of stable disease-calls for the development of molecularly informed real-time minimally invasive approaches. In addition to capturing tumor regression, liquid biopsies may be informative in capturing immune-related adverse events (irAE). EXPERIMENTAL DESIGN: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. RESULTS: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank P = 0.0003) and overall survival (log-rank P = 0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, on-treatment peripheral blood T-cell repertoire reshaping, assessed by significant T-cell receptor (TCR) clonotypic expansions and regressions, was identified on average 5 months prior to clinical diagnosis of an irAE. CONCLUSIONS: Molecular responses assist with the interpretation of heterogeneous clinical responses, especially for patients with stable disease. Our complementary assessment of the peripheral tumor and immune compartments provides an approach for monitoring of clinical benefits and irAEs during immunotherapy.

Clinical and Genomic Characterization of Long-Term Responders Receiving Immune Checkpoint Blockade for Metastatic Non-Small-Cell Lung Cancer.

OBJECTIVES: Understand from a real-world cohort the unique clinical and genomic determinants of a durable response to immune checkpoint inhibitors (ICIs). MATERIALS AND METHODS: This is a retrospective study of patients with NSCLC who received any ICI-based regimen as first or second line therapy. Long-term responders (LTR) achieved an overall survival (OS) ≥ 3 years from time of treatment start, while nonresponders (NR) were patients who had an OS of 6 to 12 months from time of treatment start. Clinical and demographic covariables were collected from electronic medical records. Fisher's exact test and Mann-Whitney test were used to analyze the association of a long-term response to ICI in relation to clinical and genomic variables. All P-values were considered significant at P-value < .05. RESULTS: A total of 72 patients were included in this study (LTR n = 37, NR n = 35). There were no significant differences in age, sex, race, and BMI between groups. The presence of liver metastases at the time of ICI initiation and PD-L1 status were not associated with LTR to ICIs. Patients in the LTR were more likely to experience irAEs at 3-,6- and 12-months. KRAS mutant tumors were numerically more common in the LTR group (n = 13 vs. 8). CONCLUSION: We observe no strong clinical and biomarkers of a prolonged response to ICIs. Additional large prospective cohort studies are needed to investigate the genomic footprint of long-term responders.

Improved lung cancer clinical outcomes in patients with autoimmune rheumatic diseases.

PURPOSE: Concomitant autoimmune rheumatic diseases (ARD) can add morbidity and complicate treatment decisions for patients with lung cancer. We evaluated the tumour characteristics at diagnosis and clinical outcomes in lung cancer patients with or without ARD. METHODS: This retrospective cohort study included 10 963 patients with lung cancer, treated at Johns Hopkins. Clinical data including tumour characteristics and outcomes were extracted from the cancer registry. Data on patients' history of 20 ARD were extracted from the electronic medical record. Logistic regression was used to compare tumour characteristics between those with and without ARD; Kaplan-Meier curves and Cox proportional hazards models were performed to compare survival outcomes. RESULTS: ARD was present in 3.6% of patients (n=454). The mean age at diagnosis was 69 (SD 10) and 68 (SD 12) in patients with and without ARD (p=0.02). Female sex and smoking history were significantly associated with a history of ARD (OR: 1.75, OR: 1.46, p<0.05). Patients with ARD were more likely to be diagnosed with stage 1 lung cancer (36.8% vs 26.9%, p<0.001) and with smaller tumour size (OR: 0.76, p=0.01), controlling for sex, race and histology. Notably, lung cancer patients with ARD had a significantly prolonged median overall survival (OS) (7.11 years vs 1.7 years, p<0.001), independent of stage. CONCLUSION: Patients with ARD and lung cancer had better OS compared with their counterparts, independent of cancer stage and treatments and were less likely to have advanced stage lung cancer at diagnosis. Additional studies are needed to investigate the differential immunological anti-tumour immune activity and genomic variations in patients with and without ARD.

ctDNA response after pembrolizumab in non-small cell lung cancer: phase 2 adaptive trial results.

Circulating tumor DNA (ctDNA) has shown promise in capturing primary resistance to immunotherapy. BR.36 is a multi-center, randomized, ctDNA-directed, phase 2 trial of molecular response-adaptive immuno-chemotherapy for patients with lung cancer. In the first of two independent stages, 50 patients with advanced non-small cell lung cancer received pembrolizumab as standard of care. The primary objectives of stage 1 were to ascertain ctDNA response and determine optimal timing and concordance with radiologic Response Evaluation Criteria in Solid Tumors (RECIST) response. Secondary endpoints included the evaluation of time to ctDNA response and correlation with progression-free and overall survival. Maximal mutant allele fraction clearance at the third cycle of pembrolizumab signified molecular response (mR). The trial met its primary endpoint, with a sensitivity of ctDNA response for RECIST response of 82% (90% confidence interval (CI): 52-97%) and a specificity of 75% (90% CI: 56.5-88.5%). Median time to ctDNA response was 2.1 months (90% CI: 1.5-2.6), and patients with mR attained longer progression-free survival (5.03 months versus 2.6 months) and overall survival (not reached versus 7.23 months). These findings are incorporated into the ctDNA-driven interventional molecular response-adaptive second stage of the BR.36 trial in which patients at risk of progression are randomized to treatment intensification or continuation of therapy. ClinicalTrials.gov ID: NCT04093167 .

Classification of Distal Clavicle Fractures and Indications for Conservative Treatment.

Management of distal clavicle fractures depends on a clear understanding of the injury's proximity to the ligamentous attachments joining the clavicle and scapula. Various classification systems have been proposed to guide treatment. Despite this, controversy between operative and nonoperative management remains for certain fracture patterns. Patient-specific factors, concomitant injuries, fracture characteristics (displacement, shortening, and rotation) should all be considered when deciding on treatment. When nonoperative management is indicated, patients should be immobilized in a sling for 2 weeks, followed by gradual range of motion, and strengthening exercises.

Phase II Randomized Trial of Carboplatin, Pemetrexed, and Bevacizumab With and Without Atezolizumab in Stage IV Nonsquamous Non-Small-Cell Lung Cancer Patients Who Harbor a Sensitizing EGFR Mutation or Have Never Smoked.

INTRODUCTION: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab. METHODS: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response. CONCLUSION: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024.

Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer.

Purpose: Although immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect -especially in the setting of stable disease-call for the development of molecularly-informed real-time minimally invasive predictive biomarkers. In addition to capturing tumor regression, liquid biopsies may be informative in evaluating immune-related adverse events (irAEs). Experimental design: We investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response for each patient. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. Results: Molecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank p=0.0003) and overall survival (log-rank p=0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, peripheral blood T-cell repertoire reshaping, assessed by significant TCR clonotypic expansions and regressions were noted on-treatment. Conclusions: Molecular responses assist with interpretation of heterogeneous clinical responses especially for patients with stable disease. Our complementary assessment of the tumor and immune compartments by liquid biopsies provides an approach for monitoring of clinical benefit and immune-related toxicities for patients with NSCLC receiving immunotherapy. Statement of translational relevance: Longitudinal dynamic changes in cell-free tumor load and reshaping of the peripheral T-cell repertoire capture clinical outcomes and immune-related toxicities during immunotherapy for patients with non-small cell lung cancer.

Stiffness and Instability After MPFL Reconstruction Using a Fluoroscopic Versus Open Technique to Localize the Femoral Attachment Site: A Systematic Review and Meta-analysis.

Background: Open and fluoroscopic techniques have been described for localization of the femoral attachment site in medial patellofemoral ligament (MPFL) reconstruction. No study to date has evaluated if one technique is superior to another in terms of complications. Purpose: To review the literature comparing clinical outcomes of MPFL reconstruction using the fluoroscopic versus open technique to localize the site of femoral graft placement. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic literature review was performed via PubMed, Embase, and CINAHL to identify articles published between the inception of these databases and March 1, 2022, in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. This search yielded 4183 publications for initial review. Studies with at least a 2-year follow-up and complete reporting of patient-reported outcomes, range of motion, recurrent instability, and/or complications (ie, stiffness, infection, persistent pain) were included. We excluded studies of patients with collagen disorders; revision surgeries; surgeries with concomitant procedures; synthetic MPFL reconstruction; MPFL repairs; combined open and radiographic technique; and case series that included <10 patients. A proportional meta-analysis was performed by calculating the pooled estimate of incidence with 95% CIs using a fixed-effects model with double arcsine transformation (Freeman-Tukey) for each type of surgical technique (fluoroscopic or open). Results: A total of 29 studies met our inclusion criteria, of which 15 studies (566 patients) used the open technique and 14 studies (620 patients) used fluoroscopy. There were no significant differences between the open and fluoroscopic techniques in the incidence of postoperative apprehension (P = .4826), postoperative subjective instability (P = .1095), postoperative objective instability (P = .5583), reoperations (P = .7981), recurrent dislocation (P = .6690), or arthrofibrosis (P = .8118). Conclusion: Both open and radiographic localization of the femoral graft position in MPFL reconstruction offer similar outcomes and rates of complications.

Antibody-Drug Conjugates for Lung Cancer: Payloads and Progress.

Antibody Drug Conjugates (ADCs) are a novel class of therapeutic that structurally comprise an antibody directed at a tumor epitope connected via a linker to a cytotoxic payload that have shown significant antitumor activity across a range of malignancies including lung cancer. In this article we review the pharmacology of ADCs, describe results of trials with ADCs directed at targets in lung cancer including Trophoblast cell-surface antigen 2(TROP2), HER3, MET, Carcinoembryonic antigen-related cell adhesion molecular 5(CECAM-5) and HER2. Trastuzumab Deruxtecan (also known as DS-8201a or T-DXd) an ADC directed at HER2 recently became the first ADC to receive FDA approval in lung cancer, on the basis of its activity in tumors with HER2 mutations, demonstrated in the Destiny-Lung01 and Lung02 trials.