Exploring the molecular landscape of cancer of unknown primary: A comparative analysis with other metastatic cancers.

Cancer of unknown primary (CUP) tumors are biologically very heterogeneous, which complicates stratification of patients for treatment. Consequently, these patients face limited treatment options and a poor prognosis. With this study, we aim to expand on the current knowledge of CUP biology by analyzing two cohorts: a well-characterized cohort of 44 CUP patients, and 213 metastatic patients with known primary. These cohorts were treated at the same institution and characterized by identical molecular assessments. Through comparative analysis of genomic and transcriptomic data, we found that CUP tumors were characterized by high expression of immune-related genes and pathways compared to other metastatic tumors. Moreover, CUP tumors uniformly demonstrated high levels of tumor-infiltrating leukocytes and circulating T cells, indicating a strong immune response. Finally, the genetic landscape of CUP tumors resembled that of other metastatic cancers and demonstrated mutations in established cancer genes. In conclusion, CUP tumors possess a distinct immunophenotype that distinguishes them from other metastatic cancers. These results may suggest an immune response in CUP that facilitates metastatic tumor growth while limiting growth of the primary tumor.

Whole-genome Mutational Analysis for Tumor-informed Detection of Circulating Tumor DNA in Patients with Urothelial Carcinoma.

BACKGROUND AND OBJECTIVE: Circulating tumor DNA (ctDNA) can be used for sensitive detection of minimal residual disease (MRD). However, the probability of detecting ctDNA in settings of low tumor burden is limited by the number of mutations analyzed and the plasma volume available. We used a whole-genome sequencing (WGS) approach for ctDNA detection in patients with urothelial carcinoma. METHODS: We used a tumor-informed WGS approach for ctDNA-based detection of MRD and evaluation of treatment responses. We analyzed 916 longitudinally collected plasma samples from 112 patients with localized muscle-invasive bladder cancer who received neoadjuvant chemotherapy (NAC) before radical cystectomy. Recurrence-free survival (primary endpoint), overall survival, and ctDNA dynamics during NAC were assessed. KEY FINDINGS AND LIMITATIONS: We found that WGS-based ctDNA detection is prognostic for patient outcomes with a median lead time of 131 d over radiographic imaging. WGS-based ctDNA assessment after radical cystectomy identified recurrence with sensitivity of 91% and specificity of 92%. In addition, genomic characterization of post-treatment plasma samples with a high ctDNA level revealed acquisition of platinum therapy-associated mutational signatures and copy number variations not present in the primary tumors. The sequencing depth is a limitation for studying tumor evolution. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our results support the use of WGS for ultrasensitive ctDNA detection and highlight the possibility of plasma-based tracking of tumor evolution. WGS-based ctDNA detection represents a promising option for clinical use owing to the low volume of plasma needed and the ease of performing WGS, eliminating the need for personalized assay design. PATIENT SUMMARY: Detection of tumor DNA in blood samples from patients with cancer of the urinary tract is associated with poorer outcomes. Disease recurrence after surgery can be identified by the presence of tumor DNA in blood before it can be detected on radiography scans.

"Trend" Statement Use in the Orthopaedic Literature.

INTRODUCTION: For research to effectively guide clinical decision making, appropriate interpretation of data is paramount. The P-value is a useful tool for guiding the interpretation of data. However, despite its utility, the P-value is not without limitations. Of particular concern is the use of "trend statements" to describe non-statistically significant findings, a practice which introduces subjectivity and variability into data interpretation and can lead to the drawing of undue conclusions. METHODS: An audit of original research articles published from January 2022 to December 2022 in four high-impact orthopaedic journals was conducted. The selected journals were queried to identify instances in which a non-statistically significant result was labeled as a "trend." The use of trend statements and associated information was recorded and analyzed. RESULTS: One thousand two hundred sixty articles were included in the analysis. 81 articles (6.4%) included a trend statement to describe a non-statistically significant result. Only two articles (2.5%) formally defined what constituted a trend. In 28.8% of cases, the associated P-value was > 0.10. DISCUSSION: Trend statements are used to describe non-statistically significant findings with moderate frequency in the orthopaedic literature. Given the potentially misleading effects of trend statements, efforts should be made to mitigate their use. If trend statements are to be used, attention should be paid to defining what constitutes a "trend", explicitly acknowledging the lack of statistical significance of the finding to which the trend statement refers, and avoiding drawing undue conclusions from non-statistically significant data.

Exploring the tumor genomic landscape of aggressive prostate cancer by whole-genome sequencing of tissue or liquid biopsies.

Treatment resistance remains a major issue in aggressive prostate cancer (PC), and novel genomic biomarkers may guide better treatment selection. Circulating tumor DNA (ctDNA) can provide minimally invasive information about tumor genomes, but the genomic landscape of aggressive PC based on whole-genome sequencing (WGS) of ctDNA remains incompletely characterized. Thus, we here performed WGS of tumor tissue (n = 31) or plasma ctDNA (n = 10) from a total of 41 aggressive PC patients, including 11 hormone-naïve, 15 hormone-sensitive, and 15 castration-resistant patients. Across all variant types, we found progressively more altered tumor genomic profiles in later stages of aggressive PC. The potential driver genes most frequently affected by single-nucleotide variants or insertions/deletions included the known PC-related genes TP53, CDK12, and PTEN and the novel genes COL13A1, KCNH3, and SENP3. Etiologically, aggressive PC was associated with age-related and DNA repair-related mutational signatures. Copy number variants most frequently affected 14q11.2 and 8p21.2, where no well-recognized PC-related genes are located, and also frequently affected regions near the known PC-related genes MYC, AR, TP53, PTEN, and BRCA1. Structural variants most frequently involved not only the known PC-related genes TMPRSS2 and ERG but also the less extensively studied gene in this context, PTPRD. Finally, clinically actionable variants were detected throughout all stages of aggressive PC and in both plasma and tissue samples, emphasizing the potential clinical applicability of WGS of minimally invasive plasma samples. Overall, our study highlights the feasibility of using liquid biopsies for comprehensive genomic characterization as an alternative to tissue biopsies in advanced/aggressive PC.

Graft Resorption After Posterior Distal Tibial Allograft Augmentation for Posterior Shoulder Instability: A Case Report.

CASE: A 19-year-old man underwent arthroscopic posterior glenoid reconstruction with a distal tibia allograft (DTA) after failing 2 posterior, soft-tissue instability surgeries. Although he experienced near-complete resolution of symptoms and return to sport, graft resorption was noted 7 months postoperatively. The patient underwent revision surgery for screw removal. CONCLUSION: Graft resorption has not previously been reported in the setting of arthroscopic DTA use for posterior instability. It is believed that stress shielding contributed to resorption. In such situations, screw removal may be warranted. Consideration of alternative fixation techniques and additional investigation into the causes, clinical significance, and optimal management of posterior DTA resorption are warranted.

Field Cancerization Is Associated with Tumor Development, T-cell Exhaustion, and Clinical Outcomes in Bladder Cancer.

BACKGROUND: Field cancerization is characterized by areas of normal tissue affected by mutated clones. Bladder field cancerization may explain the development and recurrence of bladder cancer and may be associated with treatment outcomes. OBJECTIVE: To investigate the predictive and prognostic roles of field cancerization in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) treated with bacillus Calmette-Guérin (BCG). DESIGN, SETTING, AND PARTICIPANTS: We conducted comprehensive genomic and proteomic analyses for 751 bladder biopsies and 234 urine samples from 136 patients with NMIBC. The samples were collected at multiple time points during the disease course. Field cancerization in normal-appearing bladder biopsies was measured using deep-targeted sequencing and error correction models. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Endpoints included the rates of recurrence and progression. Cox regression and Wilcoxon rank-sum and Fisher's exact tests were used. RESULTS AND LIMITATIONS: A high level of field cancerization was associated with high tumor mutational burden (p = 0.007), high tumor neoantigen load (p = 0.029), and high tumor-associated CD8 T-cell exhaustion (p = 0.017). In addition, high field cancerization was associated with worse short-term outcomes (p = 0.029). Nonsynonymous mutations in bladder cancer-associated genes such as KDM6A, ARID1A, and TP53 were identified as early disease drivers already found in normal-appearing bladder biopsies. Urinary tumor DNA (utDNA) levels reflected the bladder tumor burden and originated from tumors and field cancerization. High levels of utDNA after BCG were associated with worse clinical outcomes (p = 0.027) and with disease progression (p = 0.003). High field cancerization resulted in high urinary levels of proteins associated with angiogenesis and proliferation. Limitations include variation in the number of biopsies and time points analyzed. CONCLUSIONS: Field cancerization levels are associated with tumor development, immune responses, and clinical outcomes. utDNA measurements can be used to monitor disease status and treatment response. PATIENT SUMMARY: Molecular changes in the tissue lining the bladder result in tumor recurrence. Urinary measurements may be used to monitor bladder cancer status and treatment responses.

Post-operative Baseplate Radiographic Evaluation Using Routine pre-Operative CT.

Background: There is limited data evaluating post-operative component position and fixation in reverse shoulder arthroplasty (RSA). Therefore, the purpose of this study was to evaluate baseplate position and fixation using routine pre-operative CT and post-operative radiographs. Methods: A retrospective analysis of a series consecutive patient who underwent primary RSA was performed. Pre-operative and post-operative glenoid retroversion and inclination were measured using radiographs aligned with projection silhouettes of 3D scapula models in Mimics software. Baseplate retroversion and inclination were measured followed by evaluating for the presence of radiolucent lines (RLLs). Results: Twenty-four patients met inclusion criteria. The average age was 73.4 ± 10.7 years (range, 45-89 years). Radiographic follow-up was 3.4 ± 1.3 years. Post-operative glenoid baseplate retroversion was 2 ± 10 degrees (range, 30 to -9). Post-operative glenoid baseplate inclination was 3.8 ± 9.1 (range, -13 to 19). Five (21%) RSAs had baseplate retroversion >10 degrees. Follow-up radiographs revealed no RLLs around the baseplate, central post, or peripheral screws in any patient. Conclusions: Pre-operative CT imaging enabled evaluation of baseplate component placement and fixation on post-operative radiographs. Baseplate version was within 10 degrees of neutral in 79% (19/24) of patients. No RLLs or loss of fixation were found in any cases. Level of Evidence: Level IV: Diagnostic Study.

Meniscal Injuries Are Decreasing but Are Increasingly Being Treated Surgically With Excellent Return to Play Rates in Professional Baseball Players.

Purpose: The purposes of this study were to determine the incidence and key characteristics of meniscus injuries in professional baseball players, assess current treatment strategies, determine the return to play rates at any level (RTP) and at the same level (RSL), and identify prognostic factors that predict injury severity. Methods: After approval from the Major League Baseball (MLB) Research Committee and our institutional review board, the MLB Health and Injury Tracking System was used to identify meniscus injuries occurring across MLB and Minor League Baseball (MiLB) from 2011 to 2017. Analyzed injuries occurred during normal baseball activity in a player who was active on an MLB or MiLB roster and resulted in at least 1 day missed. Results: A total of 293 professional baseball players sustained 314 meniscus injuries from 2011 to 2017 (7 years) for a mean of 44.9 injuries/y. Pitchers were the most injured position (31.8%), followed by infielders (26.4%). Catchers and infielders missed the most median number of days (50 days). When comparing injuries to landing leg vs push-off leg in pitchers, injury to the push-off leg resulted in significantly more days missed per injury compared to the lead leg (59.6 vs 39.9 days, P = .048). Overall, RTP was 93.0%, while RSL was 84.4%. Conclusions: Over 7 professional baseball seasons, 314 meniscus injuries occurred in 293 players. Pitchers and catchers were most injured, and overall, the number of meniscal injuries per year declined while the percentage of injuries that required surgery increased over time. High rates of RTP were observed. Level of Evidence: Level IV, therapeutic case series.

Circular stable intronic RNAs possess distinct biological features and are deregulated in bladder cancer.

Until recently, intronic lariats were regarded as short-lasting splicing byproducts with no apparent function; however, increasing evidence of stable derivatives suggests regulatory roles. Yet little is known about their characteristics, functions, distribution, and expression in healthy and tumor tissue. Here, we profiled and characterized circular stable intronic sequence RNAs (sisRNAs) using total RNA-Seq data from bladder cancer (BC; n = 457, UROMOL cohort), healthy tissue (n = 46), and fractionated cell lines (n = 5). We found that the recently-discovered full-length intronic circles and the stable lariats formed distinct subclasses, with a surprisingly high intronic circle fraction in BC (∼45%) compared to healthy tissues (0-20%). The stable lariats and their host introns were characterized by small transcript sizes, highly conserved BP regions, enriched BP motifs, and localization in multiple cell fractions. Additionally, circular sisRNAs showed tissue-specific expression patterns. We found nine circular sisRNAs as differentially expressed across early-stage BC patients with different prognoses, and sisHNRNPK expression correlated with progression-free survival. In conclusion, we identify distinguishing biological features of circular sisRNAs and point to specific candidates (incl. sisHNRNPK, sisWDR13 and sisMBNL1) that were highly expressed, had evolutionary conserved sequences, or had clinical correlations, which may facilitate future studies and further insights into their functional roles.

Sub-hourly measurement datasets from 6 real buildings: Energy use and indoor climate.

The data presented here were collected independently for 6 real buildings by researchers of different institutions and gathered in the context of the IEA EBC Annex 81 Data-driven Smart Buildings, as a joint effort to compile a diverse range of datasets suitable for advanced control applications of indoor climate and energy use in buildings. The data were acquired by energy meters, both consumption and PV generation, and sensors of technical installation and indoor climate variables, such as temperature, flow rate, relative humidity, CO2 level, illuminance. Weather variables were either acquired by local sensors or obtained from a close by meteorological station. The data were collected either during normal operation of the building, with observation periods between 2 weeks and 2 months, or during experiments designed to excite the thermal mass of the building, with observation periods of approximately one week. The data have a time resolution varying between 1 min and 15 min; in some case the highest resolution data are also averaged at larger intervals, up to 30 min.

Single-nucleus and Spatially Resolved Intratumor Subtype Heterogeneity in Bladder Cancer.

Background: Current bulk transcriptomic classification systems for bladder cancer do not consider the level of intratumor subtype heterogeneity. Objective: To investigate the extent and possible clinical impact of intratumor subtype heterogeneity across early and more advanced stages of bladder cancer. Design setting and participants: We performed single-nucleus RNA sequencing (RNA-seq) of 48 bladder tumors and additional spatial transcriptomics for four of these tumors. Total bulk RNA-seq and spatial proteomics data were available from the same tumors for comparison, along with detailed clinical follow-up of the patients. Outcome measurements and statistical analysis: The primary outcome was progression-free survival for non-muscle-invasive bladder cancer. Cox regression analysis, log-rank tests, Wilcoxon rank-sum tests, Spearman correlation, and Pearson correlation were used for statistical analysis. Results and limitations: We found that the tumors exhibited varying levels of intratumor subtype heterogeneity and that the level of subtype heterogeneity can be estimated from both single-nucleus and bulk RNA-seq data, with high concordance between the two. We found that a higher class 2a weight estimated from bulk RNA-seq data is associated with worse outcome for patients with molecular high-risk class 2a tumors. The sparsity of the data generated using the DroNc-seq sequencing protocol is a limitation. Conclusions: Our results indicate that discrete subtype assignments from bulk RNA-seq data may lack biological granularity and that continuous class scores may improve clinical risk stratification of patients with bladder cancer. Patient summary: We found that several molecular subtypes can exist within a single bladder tumor and that continuous subtype scores can be used to identify a subgroup of patients with poor outcomes. Use of these subtype scores may improve risk stratification for patients with bladder cancer, which can help in making decisions on treatment.

Improved protocol for single-nucleus RNA-sequencing of frozen human bladder tumor biopsies.

This paper provides a laboratory workflow for single-nucleus RNA-sequencing (snRNA-seq) including a protocol for gentle nuclei isolation from fresh frozen tumor biopsies, making it possible to analyze biobanked material. To develop this protocol, we used non-frozen and frozen human bladder tumors and cell lines. We tested different lysis buffers (IgePal and Nuclei EZ) and incubation times in combination with different approaches for tissue and cell dissection: sectioning, semi-automated dissociation, manual dissociation with pestles, and semi-automated dissociation combined with manual dissociation with pestles. Our results showed that a combination of IgePal lysis buffer, tissue dissection by sectioning, and short incubation time was the best conditions for gentle nuclei isolation applicable for snRNA-seq, and we found limited confounding transcriptomic changes based on the isolation procedure. This protocol makes it possible to analyze biobanked material from patients with well-described clinical and histopathological information and known clinical outcomes with snRNA-seq.

Cell-Free Urine and Plasma DNA Mutational Analysis Predicts Neoadjuvant Chemotherapy Response and Outcome in Patients with Muscle-Invasive Bladder Cancer.

PURPOSE: To investigate the use of plasma and urine DNA mutation analysis for predicting neoadjuvant chemotherapy (NAC) response and oncological outcome in patients with muscle-invasive bladder cancer. EXPERIMENTAL DESIGN: Whole-exome sequencing of tumor and germline DNA was performed for 92 patients treated with NAC followed by radical cystectomy (RC). A custom NGS-panel capturing approximately 50 mutations per patient was designed and used to track mutated tumor DNA in plasma and urine. A total of 447 plasma samples, 281 urine supernatants, and 123 urine pellets collected before, during, and after treatment were analyzed. Patients were enrolled from 2013 to 2019, with a median follow-up time of 41.3 months after RC. RESULTS: We identified tumor DNA before NAC in 89% of urine supernatants, 85% of urine pellets, and 43% of plasma samples. Tumor DNA levels were higher in urine supernatants and urine pellets compared with plasma samples (P < 0.001). In plasma, detection of circulating tumor DNA (ctDNA) before NAC was associated with a lower NAC response rate (P < 0.001). Detection of tumor DNA after NAC was associated with lower response rates in plasma, urine supernatant, and urine pellet (P < 0.001, P = 0.03, P = 0.002). Tumor DNA dynamics during NAC was predictive of NAC response and outcome in urine supernatant and plasma (P = 0.006 and P = 0.002). A combined measure from plasma and urine supernatant tumor DNA dynamics stratified patients by outcome (P = 0.003). CONCLUSIONS: Analysis of tumor DNA in plasma and urine samples both separately and combined has a potential to predict treatment response and outcome.

Noninvasive prenatal screening for cystic fibrosis using circulating trophoblasts: Detection of the 50 most common disease-causing variants.

OBJECTIVES: Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders. Prenatal or preconception CF screening is offered in some countries. A maternal blood sample in early pregnancy can provide circulating trophoblasts and offers a DNA source for genetic analysis of both the mother and the fetus. This study aimed to develop a cell-based noninvasive prenatal test (NIPT) to screen for the 50 most common CF variants. METHODS: Blood samples were collected from 30 pregnancies undergoing invasive diagnostics and circulating trophoblasts were harvested in 27. Cystic fibrosis testing was conducted using two different methods: by fragment length analysis and by our newly developed NGS-based CF analysis. RESULTS: In all 27 cases, cell-based NIPT provided a result using both methods in agreement with the invasive test result. CONCLUSION: This study shows that cell-based NIPT for CF screening provides a reliable result without the need for partner- and proband samples.

Rare Case of a Turner Syndrome Patient with Metastatic Dysgerminoma and No Y-Chromosomal Material with Pathogenic Variants Found in KIT and MTOR.

INTRODUCTION: The presence of Y-chromosomal material in females with Turner syndrome (TS) is a well-established risk factor for developing gonadoblastoma and malignant transformations thereof. However, these events are rarely seen in TS patients with no Y-chromosomal material. Thus, it is the current understanding that parts of the Y-chromosome are essential for the malignant transformation of gonadoblastoma in the dysgenetic gonad. METHODS: We report a case of a TS female with an apparent 46,X,idic(Xq) karyotype, who was diagnosed with a metastatic dysgerminoma. Whole exome sequencing of the tumor and blood, along with RNA sequencing of the tumor, was performed to comprehensively search for cryptic Y-chromosomal material and pathogenic variants. RESULTS: No Y-chromosomal material was detected in either tumor or blood. Whole exome-sequencing of DNA and RNA revealed a pathogenic somatic gain-of-function mutation in KIT and a pathogenic missense mutation in MTOR. The patient underwent total hysterectomy with bilateral salpingo-oophorectomy, followed by adjuvant chemotherapy. Unfortunately, she died due to chemotherapy-induced pneumonitis 7 months after the initial diagnosis. CONCLUSION: Females with TS can develop metastatic dysgerminoma even in the absence of Y-chromosomal material. This questions the current understanding of Y-chromosomal material being essential for the malignant transformation of a gonadoblastoma in the dysgenetic gonad.

Shoulder Injuries in Professional Baseball Batters: Analysis of 3,414 Injuries Over an 8-Year Period.

Purpose: To characterize the shoulder injuries experienced by baseball batters and position players (nonpitchers); to quantify the outcomes of these injuries with respect to time out of play, recurrence, and surgery rates; and to identify any injury patterns that are associated with worse outcomes. Methods: Between 2011 and 2017, all Major League Baseball (MLB) and Minor League Baseball (MiLB) players who sustained shoulder injuries were identified using the MLB Health and Injury Tracking System (HITS). Injuries were included if they were sustained during baseball activity, resulted in at least 1 day missed (DM), and occurred in position players (nonpitchers). Results: Over the study period, a total of 3,414 shoulder injuries occurred in batters, resulting in a sum of 68,808 DM and a mean of 22 DM per injury. Most injuries were a result of acute trauma (n = 2125; 62.2%) with throwing as the predominant activity (n = 1292; 38%). Rotator cuff strain/tears was the most common diagnosis (n = 790; 23.1%), and SLAP tears had the highest season-ending rate (35.3%) and need for surgery (45.1%). There was a lower frequency of surgery (6.2% vs 9.2%; P = .002) and reinjury (2.03% vs 3.62%; P = .007) in the throwing shoulder vs the nonthrowing shoulder. There was an increased frequency of surgery for the front versus the back batting shoulder (8.2% vs 6.2%; P = .031) with similar DM (20.7 vs 22.2; P = .333) and return to play rates (94.0% vs 92.2%; P = .135). Conclusions: During the 7-season study period, there were a total of 3,414 shoulder injuries that resulted in nearly 70,000 days of out of play in professional baseball position players/batters (nonpitchers). Although pitchers were intentionally excluded from the analysis, throwing was still the most common mechanism of injury, and rotator cuff injuries were the most common injury. Labral tears were the most likely injury to be season ending and require surgery. Clinical Relevance: This study is meant to help determine characteristics of shoulder injuries that occur in non-pitchers by focusing on professional baseball batters and position players. This information could be helpful to sports medicine practitioners and shoulder specialists to better prognosticate injury recovery.

Early career opportunities and practice characteristics of recent graduates of shoulder and elbow fellowship programs.

BACKGROUND: There exists anecdotal evidence that influential faculty members actively dissuade orthopedic surgery residents from pursuing a fellowship in shoulder and elbow due to a perceived lack of availability of jobs following graduation. The aims of the present study are to evaluate whether this perception is true by characterizing the early career opportunities and practice characteristics of recent graduates of shoulder and elbow fellowship programs through a survey of graduates of the past 5 years. METHODS: An anonymous 39-question survey was designed and approved by the leadership of the American Shoulder and Elbow Surgeons (ASES). The survey was distributed via electronic mail to the fellowship directors and coordinators of the 31 ASES-recognized shoulder and elbow fellowship programs. The fellowship directors and coordinators then sent the survey to the shoulder and elbow fellowship graduates of the last 5 years (2016-2020). Following a total of 4 emails, the survey closed after 8 weeks, and descriptive statistical analysis was performed. RESULTS: Seventy-six of 171 (44.4%) fellows responded. In total, 89.5% were very or somewhat satisfied with their fellowship experience, and 90.8% would pursue a shoulder and elbow fellowship again. Notably, 100% of shoulder and elbow fellowship graduates surveyed in the past 5 years have secured employment. The average number of total orthopedic and shoulder and elbow cases performed annually was 296.7 (SD 141.3) and 173.9 (SD 120.2), respectively. In addition, 62.7% and 89% of respondents were very or somewhat satisfied with the volume and surgical complexity of shoulder and elbow cases, respectively. For the fellows that believed their case experience to be inadequate, the most common reasons were competition from other practices (66.0%) and inadequate patient volume (59.6%). CONCLUSION: Recent graduates of the ASES-recognized shoulder and elbow fellowship programs demonstrate a high level of satisfaction with the fellowship and their subspeciality selection. The majority of fellows believed that completing a shoulder and elbow fellowship enhanced their job opportunities. Altogether, there are ample job opportunities and high satisfaction with the volume and complexity of cases as an early career shoulder and elbow surgeon.

Circulating tumor DNA for prognosis assessment and postoperative management after curative-intent resection of colorectal liver metastases.

The recurrence rate of colorectal liver metastases (CRLM) patients treated with curative intent is above 50%. Standard of care surveillance includes intensive computed tomographic (CT) imaging as well as carcinoembryonic antigen (CEA) measurements. Nonetheless, relapse detection often happens too late to resume curative treatment. This longitudinal cohort study enrolled 115 patients with plasma samples (N = 439) prospectively collected before surgery, postoperatively at day 30 and every third month for up to 3 years. Droplet digital PCR (ddPCR) was used to monitor serial plasma samples for somatic mutations. Assessment of ctDNA status either immediately after surgery, or serially during surveillance, stratified the patients into groups of high and low recurrence risk (hazard ratio [HR], 7.6; 95% CI, 3.0-19.7; P < .0001; and HR, 4.3; 95% CI, 2.3-8.1; P < .0001, respectively). The positive predictive value (PPV) of ctDNA was 100% in all postoperative analyses. In multivariable analyses, postoperative ctDNA status was the only consistently significant risk marker associated with relapse (P < .0001). Indeterminate CT findings were observed for 30.8% (21/68) of patients. All patients (9/21) that were ctDNA positive at the time of the indeterminate CT scan later relapsed, contrasting 42.6% (5/12) of those ctDNA negative (P = .0046). Recurrence diagnoses in patients with indeterminate CT findings were delayed (median 2.8 months, P < .0001). ctDNA status is strongly associated with detection of minimal residual disease and early detection of relapse. Furthermore, ctDNA status can potentially contribute to clinical decision-making in case of indeterminate CT findings, reducing time-to-intervention.

Endosteal plating in proximal humerus fractures: a novel technique and alternative to fibular strut allograft for medial column support.

Hypothesis: The purpose of this retrospective study is to investigate the clinical and radiographic outcomes associated with the use of a standard metal plate as an endosteal implant in combination with a lateral locking plate to treat 4 patients with displaced proximal humerus fractures. Methods: A retrospective case series study design was utilized, and the medical records of 4 patients with displaced, 3-part proximal humerus fractures treated using this technique between January 2019 and July 2021 were reviewed for this study. The mean age was 52 years (range, 44-57 years). The radiographic outcome of interest was humeral neck-shaft angle preoperatively, intraoperatively, and at the latest follow-up. The average follow-up duration was 62 weeks (range, 12-161 weeks). Results: All fractures healed without loss of reduction or neurovascular deficits. Avascular necrosis was not observed in the 2 patients with sufficient follow-up time to make such an evaluation. The average neck-shaft angles preoperatively, intraoperatively, and at the latest follow-up were 104.8°, 139.8°, and 137°, respectively. Conclusion: Locking plate technology augmented with an endosteal plate provided stable reduction and restoration of physiologic alignment in a small number of patients with displaced proximal humerus fractures. This construct creates a second column of fixation, providing medial column support, and could be removed in the event of a future revision to a reverse shoulder arthroplasty.