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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

IntroductionThe magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower response rates and decreased survival after ICI monotherapy. The mechanisms underlying this sex dimorphism in ICI response are unknown, and may be related to sex-driven differences in the immunogenomic landscape of tumors that shape anti-tumor immune responses in the context of therapy.MethodsTo investigate the association of immunogenic mutations with HLA haplotypes, we leveraged whole exome sequence data and HLA genotypes from 482 non-small cell lung cancer (NSCLC) tumors from The Cancer Genome Atlas (TCGA). To explore sex-specific genomic features linked with ICI response, we analyzed whole exome sequence data from patients with NSCLC treated with ICI. Tumor mutational burden (TMB), HLA class I and II restricted immunogenic missense mutation (IMM) load, and mutational smoking signature were defined for each tumor. IMM load was combined with HLA class I and II haplotypes and correlated with therapeutic response and survival following ICI treatment. We examined rates of durable clinical benefit (DCB) for at least six months from ICI treatment initiation. Findings were validated utilizing whole exome sequence data from an independent cohort of ICI treated NSCLC.ResultsAnalysis of whole exome sequence data from NSCLC tumors of females and males revealed that germline HLA class II diversity (≥9 unique HLA alleles) was associated with higher tumor class II IMM load in females (p=0.01) and not in males (p=0.64). Similarly, in tumors of female patients, somatic HLA class II loss of heterozygosity was associated with increased IMM load (p=0.01) while this association was not observed in tumors in males (p=0.20). In females, TMB (p=0.005), class I IMM load (p=0.005), class II IMM load (p=0.004), and mutational smoking signature (p

Anterior shoulder dislocations commonly occur in the young, athletic population. The mechanism of dislocation occurs when the shoulder is placed in an abducted, externally rotated position while a forceful anterior moment is applied to the humerus. This position, combined with the force applied, results in an anterior and inferiorly directed dislocation of the humeral head away from the glenoid. Due to the limited stretching capacity of the glenohumeral capsule and associated glenohumeral ligaments, the force of the traumatic dislocation overcomes the tensile strength of these ligaments, resulting in a tear. Although the injury more commonly results in an avulsion of the anteroinferior capsulolabral complex from the glenoid, called a Bankart lesion, other injuries have been described. The anterior inferior glenohumeral ligaments (aIGHLs), may be torn from their humeral attachment, which is referred to as a humeral avulsion of the glenohumeral ligament (HAGL). Although other structures may be injured, the topic of this surgical technique focuses on a mini-open approach for repair of the HAGL lesion.

Surgical treatment of patellofemoral instability and associated cartilaginous lesions can be technically challenging. Visualization of patellar tracking and underlying osteochondral lesions is paramount to operative success. To treat these conditions effectively, a comprehensive arthroscopic assessment of the patellofemoral joint as well as dynamic visualization of patella tracking must be achieved. Visualization of the patellofemoral joint—in particular, the articular cartilage of the patella and trochlea morphology—can be difficult when using traditional anteromedial or anterolateral portals and a 30° arthroscope lens. The technique described here uses an accessory superolateral portal and a 70° arthroscope to achieve significantly improved visualization of the patellofemoral articulation, in particular the chondral surfaces. This vantage point aids the surgeon in effectively evaluating patellar tracking, trochlea morphology, and importantly, osteochondral lesion location to help guide treatment algorithms in the patellofemoral joint.

Purpose: To evaluate the time required for colonies to develop from concentrated bone marrow aspirate (cBMA) and subacromial bursal tissue samples. Methods: Samples of cBMA and subacromial bursa tissue were harvested from patients undergoing rotator cuff repair surgery between November 2014 and December 2019. Samples were analyzed for time to form colonies and number of colonies formed. The impact of age, sex, and cellularity (cBMA only) was analyzed. Samples were cultured and evaluated daily for colony formation in accordance with the guidelines of the International Society for Cellular Therapy. Demographic factors were analyzed for impact on time to form colonies and number of colonies formed. Results: Samples of cBMA were obtained from 92 patients. Subacromial bursa tissue was obtained from 54 patients. For cBMA, older age was associated with more days to form colonies (P = .003), but sex (P = .955) and cellularity (P = .623) were not. For bursa, increased age was associated with longer time to form colonies (P = .002) but not sex (P = .804). Conclusions: Increased age (in cBMA and subacromial bursa tissue) and lower initial cellularity (in cBMA) are associated with longer time to form colonies in culture. Clinical Relevance: Although connective tissue progenitor cells are widely used in orthopaedic practice, there are few metrics to determine their efficacy. Time to form colonies may serve as an important measurement for determining connective tissue progenitor cell viability for augmentation of rotator cuff repair. Subacromial bursa tissue may represent a viable alternative to cBMA for augmentation of rotator cuff repair, capable of forming colonies expediently in vivo.

The posterolateral corner (PLC) is an important stabilizer of the knee. This complex of ligaments and tendons functions as the primary restraint to varus and posterolateral rotation of the knee. Injury to the PLC can result in chronic instability, a varus-thrust gait, and early arthrosis of the medial compartment of the knee if left untreated. Several techniques have been designed to address injuries of the PLC. Over the last 30 years, our understanding of the posterolateral corner as well as its operative reconstruction evolved. This evolution has attempted to refine what is an “anatomic” reconstruction. With more improved techniques and new, innovative fixation devices, we hope to make a more favorable repair for recreating the native stability of the posterolateral corner.

Patellar instability remains a ubiquitous and troublesome problem in orthopaedics and represents a challenge in the pediatric population. Reconstruction of the medial patellofemoral ligament (MPFL) has become a mainstay of patellar instability management in recent years. As with any procedure at or around the physes, there is concern among surgeons regarding safe placement of hardware and drilled tunnels. The authors describe a technique for anatomic MPFL reconstruction with the aid of fluoroscopic guidance to maintain a “safe zone” without violating the distal femoral physis. This technique allows for reliable MPFL reconstruction in the skeletally immature population with concomitant lateral lengthening, while requiring only minor deviations from the procedure in a skeletally mature patient.

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.

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.

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.

Introduction: Chondromalacia patellae (CP) is common among patients with anterior knee pain (AKP), characterized by softening and deterioration of the patellar cartilage. Although the exact etiology is unknown, risk factors include lower extremity muscle weakness, obesity, and female sex. Further, patellar maltracking may play a role in developing CP. Treatment algorithms for CP remain vague and inconsistent as the significance of the diagnosis remains in question. Initial treatment is typically nonoperative with various adjunct modalities. However, surgery may have a role for recalcitrant cases. Objectives: Although CP is a common diagnosis, there is still much to be learned about the significance of this diagnosis and subsequent treatment strategies. Knowledge of this will help to guide providers moving forward. Methods: The authors completed a thorough literature search of available published work through December 31, 2021, discussing CP and its relationship with AKP, and distilled this information into current concepts regarding history, diagnosis, treatment, and future directions. Results: Although much is still unknown about the significance and best treatment strategy for patients with AKP pain and CP, it is likely that in many cases chondromalacia is a finding in the presence of AKP, rather than the cause of the AKP. Conclusions: More work must be done to fully elucidate the underlying causes of CP. However, some of these cases are likely related to subtle maltracking and perhaps can be surgically corrected. In most cases, extensive nonoperative measures and searching for other causes of AKP is most prudent.

Purpose: The purposes of this study were to 1) calculate the minimal clinically important difference (MCID) in a population of patients undergoing arthroscopic partial meniscectomy (APM) based on Knee Injury and Osteoarthritis Outcomes Scores (KOOS), 2) quantify the difference between the proportion of patients reaching MCID based on KOOS versus the proportion who considered surgery to be successful based on a “yes” answer to a patient acceptable symptom state (PASS) question, and 3) calculate the percentage of patients experiencing treatment failure (TF). Methods: A large, single-institution clinical database was queried for patients undergoing isolated APM (>40 years of age). Data were collected at regular time intervals, including KOOS and PASS outcome measures. Calculation of MCID using a distribution-based model was performed using preoperative KOOS scores as baseline. Comparison of the proportion of patients surpassing MCID was made to the proportion of patients answering “yes” to a tiered PASS question at 6 months after APM. Proportion of patients experiencing TF was calculated using patients who responded “no” to a PASS question and “yes” to a TF question. Results: Three-hundred and fourteen of 969 patients met inclusion criteria. At 6 months following APM, the percentage of patients meeting or exceeding the MCID for each respective KOOS subscore ranged from 64 to 72% compared to 48% who achieved a PASS (P < .0001 for each subscore). Fourteen percent of patients experienced TF. Conclusions: Six months after APM, approximately one half of the patients achieved a PASS and 15% experienced TF. The difference between achieving MCID based on each of the KOOS subscores and achieving success via PASS ranged from 16% to 24%. Thirty-eight percent of patients undergoing APM did not fit neatly into overt success or failure categorization. Level of Evidence: Level III, retrospective cohort study.

Circulating cell-free tumor DNA (ctDNA) can serve as a real-time biomarker of tumor burden and provide unique insights into the evolving molecular landscape of cancers under the selective pressure of immunotherapy. Tracking the landscape of genomic alterations detected in ctDNA may reveal the clonal architecture of the metastatic cascade and thus improve our understanding of the molecular wiring of therapeutic responses. While liquid biopsies may provide a rapid and accurate evaluation of tumor burden dynamics during immunotherapy, the complexity of antitumor immune responses is not fully captured through single-feature ctDNA analyses. This underscores a need for integrative studies modeling the tumor and the immune compartment to understand the kinetics of tumor clearance in association with the quality of antitumor immune responses. Clinical applications of ctDNA testing in patients treated with immune checkpoint inhibitors have shown both predictive and prognostic value through the detection of genomic biomarkers, such as tumor mutational burden and microsatellite instability, as well as allowing for real-time monitoring of circulating tumor burden and the assessment of early on-therapy responses. These efforts highlight the emerging role of liquid biopsies in selecting patients for cancer immunotherapy, monitoring therapeutic efficacy, determining the optimal duration of treatment and ultimately guiding treatment selection and sequencing. The clinical translation of liquid biopsies is propelled by the increasing number of ctDNA-directed interventional clinical trials in the immuno-oncology space, signifying a critical step towards implementation of liquid biopsies in precision immuno-oncology.