miRNA panel from HER2+ and CD24+ plasma extracellular vesicle subpopulations as biomarkers of early-stage breast cancer.

Background: Mammography screening has improved early breast cancer detection, leading to reduced mortality and lower rates of advanced breast cancer. However, mammography has a high false positive rate that results in over a million invasive breast biopsies of benign lesions in the US each year. Therefore, there is a need for noninvasive, blood-based diagnostics that can accurately assess risk of malignancy for women with indeterminate lesions identified by mammography, such as BI-RADS category 4 breast lesions.

Computational pathology assessments of cardiac stromal remodeling: Clinical correlates and prognostic implications in heart transplantation.

Background: The hostile immune environment created by allotransplantation can accelerate pathologic tissue remodeling. Both overt and indolent inflammatory insults propel this remodeling, but there is a paucity of tools for monitoring the speed and severity of remodeling over time.

Methods: This retrospective cohort consisted of  = 2,167 digitized heart transplant biopsy slides along with records of prior inflammatory events and future allograft outcomes (cardiac death or allograft vasculopathy).

Optimized Whole-Slide-Image H&E Stain Normalization: A Step Towards Big Data Integration in Digital Pathology.

In the medical diagnostics domain, pathology and histology are pivotal for the precise identification of diseases. Digital histopathology, enhanced by automation, facilitates the efficient analysis of massive amount of biopsy images produced on a daily basis, streamlining the evaluation process. This study focuses in Stain Color Normalization (SCN) within a Whole-Slide Image (WSI) cohort, aiming to reduce batch biases.

Editorial Commentary: Anterior Cruciate Ligament Primary Repair Has Limited Indications and Outcomes Inferior to Anterior Cruciate Ligament Reconstruction.

The anterior cruciate ligament (ACL) primary repair literature does not convincingly show noninferiority to the gold standard of ACL reconstruction using a graft. Primary repair has narrow indications, typically a Sherman type 1 tear pattern representing a femoral avulsion with good tissue quality. In addition, recent research has shown greater postoperative laxity in repairs deemed successful in comparison to laxity in patients undergoing reconstruction.

Editorial Commentary: Biceps Management During Rotator Cuff Tear: Confounding Variables Result in Unclear Indications.

Is "killing the biceps" during rotator cuff repair a capital crime or a lawful act? One of the most passionately debated topics in shoulder surgery is what to do with the biceps during rotator cuff repair: save it, tenotomize it, or perform tenodesis. Results of repair are not very successful, and given that repair of massive rotator cuff tears shows a 40% to 57% failure rate, there is renewed interest in sparing the biceps tendon as a humeral head depressor-or so that it may be used as a local graft for revision rotator cuff repair. The literature regarding tenodesis versus biceps sparing during rotator cuff repair is controversial.

Failing to Make the Grade: Conventional Cardiac Allograft Rejection Grading Criteria Are Inadequate for Predicting Rejection Severity.

Background: Cardiac allograft rejection is the leading cause of early graft failure and is a major focus of postheart transplant patient care. While histological grading of endomyocardial biopsy samples remains the diagnostic standard for acute rejection, this standard has limited diagnostic accuracy. Discordance between biopsy rejection grade and patient clinical trajectory frequently leads to both overtreatment of indolent processes and delayed treatment of aggressive ones, spurring the need to investigate the adequacy of the current histological criteria for assessing clinically important rejection outcomes.

Inferring super-resolution tissue architecture by integrating spatial transcriptomics with histology.

Spatial transcriptomics (ST) has demonstrated enormous potential for generating intricate molecular maps of cells within tissues. Here we present iStar, a method based on hierarchical image feature extraction that integrates ST data and high-resolution histology images to predict spatial gene expression with super-resolution. Our method enhances gene expression resolution to near-single-cell levels in ST and enables gene expression prediction in tissue sections where only histology images are available.

Orthopedic surgery residents reported increased shoulder procedure volumes during the COVID-19 pandemic.

Background: The purpose of this study is to evaluate the impact of the COVID-19 pandemic on shoulder procedure volumes reported to the Accreditation Council for Graduate Medical Education by orthopedic surgery residents.

Methods: We performed a retrospective review of Accreditation Council for Graduate Medical Education case logs reporting data from graduating orthopedic surgery residents during the academic years of 2006-2022. Data were queried for all patients for the following shoulder Current Procedural Terminology codes: incision, excision, intro or removal, repair/revision/reconstruction, fracture and/or dislocation, manipulation, arthroscopy, trauma, and total procedures performed.

Clinically Significant Outcome Scores in Orthopaedic Sports Medicine Shoulder and Knee Surgery Are Increasing in Prevalence but Often Reported Incorrectly.

Purpose: To study the prevalence and quality of application of minimal clinically important difference (MCID), substantial clinical benefit (SCB), patient-acceptable symptomatic state (PASS), and maximum outcome improvement (MOI), reported in the orthopaedic sports medicine knee and shoulder literature in recent years and to bring awareness of proper use of such metrics.

Methods: A literature review of all shoulder and knee articles published from the American Journal of Sports Medicine (AJSM), Journal of Shoulder and Elbow Surgery (JSES), and Arthroscopy from 2016 to 2020 was performed, specifically investigating whether MCID, SCB, PASS, or MOI were used or reported. Additionally, the way these metrics were reported and interpreted was recorded.

Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer.

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN-) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN- IBC.

Robust Image Population Based Stain Color Normalization: How Many Reference Slides Are Enough?

Histopathologic evaluation of Hematoxylin & Eosin (H&E) stained slides is essential for disease diagnosis, revealing tissue morphology, structure, and cellular composition. Variations in staining protocols and equipment result in images with color nonconformity. Although pathologists compensate for color variations, these disparities introduce inaccuracies in computational whole slide image (WSI) analysis, accentuating data domain shift and degrading generalization.

PROTEIN KINASE C ALPHA IS A CENTRAL NODE FOR TUMORIGENIC TRANSCRIPTIONAL NETWORKS IN HUMAN PROSTATE CANCER.

Aberrant expression of protein kinase C (PKC) isozymes is a hallmark of cancer. The different members of the PKC family control cellular events associated with cancer development and progression. Whereas the classical/conventional PKCα isozyme has been linked to tumor suppression in most cancer types, here we demonstrate that this kinase is required for the mitogenic activity of aggressive human prostate cancer cells displaying aberrantly high PKCα expression.

Ruxolitinib and exemestane for estrogen receptor positive, aromatase inhibitor resistant advanced breast cancer.

Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and aromatase inhibitor (AI) resistance in hormone-receptor positive (HR+) breast cancer. Here we report the results of a phase 2 single-arm Simon 2-stage trial combining Ruxolitinib, an oral selective inhibitor of JAK1/2, with exemestane, a steroidal AI, in patients with HR+ metastatic breast cancer (MBC) after progression on non-steroidal AI (NSAI). Safety and efficacy were primary objectives, and analysis of inflammatory markers as predictors of response was a key secondary objective.

Epithelial cell size dysregulation in human lung adenocarcinoma.

Human cells tightly control their dimensions, but in some cancers, normal cell size control is lost. In this study we measure cell volumes of epithelial cells from human lung adenocarcinoma progression in situ. By leveraging artificial intelligence (AI), we reconstruct tumor cell shapes in three dimensions (3D) and find airway type 2 cells display up to 10-fold increases in volume.

Editorial Commentary: Magnetic Resonance Imaging Is Helpful in Predicting High-Grade Knee Rotatory Instability: But When in Doubt, Always Examine the Patient.

Unrecognized rotatory instability as evidenced by a high-grade pivot shift is well known to compromise anterior cruciate ligament (ACL) reconstruction results. By measuring which patients have anterior tibial subluxation of the lateral compartment ≥ 6 mm on a preoperative MRI, surgeons may be better able to counsel patients on postoperative expectations, as well as prepare for additional procedures to treat high-grade rotatory instability. Additionally, as there is an increased incidence of lateral meniscus tears in high-grade rotatory ACL lesions, surgeons should be vigilant and prepared to repair lateral meniscus root and ramp lesions.

Editorial Commentary: Free Bone Block With Remplissage Provides Less Translation Than Free Bone Block Alone in Shoulder Instability Patients With Bipolar Bone Loss.

It would stand to reason that, in shoulder instability patients with bipolar bone loss, the combination of a bone block procedure and a remplissage procedure would provide better results than each one alone. Why would this be the case? When performing these procedures in the lateral decubitus position for patients with critical bipolar bone loss, the humeral head is anteriorly and inferiorly subluxed. This is most likely due to the incompetent restraints when in traction.

Editorial Commentary: Indications for Shoulder SLAP Lesion Repair Versus Biceps Tenodesis Depend on Patient Age, Tear Type and Location, and Quality of Tissue.

Whether to repair a shoulder SLAP lesion or perform a biceps tenodesis depends on a multitude of factors: patient age, activity or work level, type of SLAP tear, location of SLAP tear, and quality of labral tissue. Determining which procedure to perform does not have such a simple, one-size-fits-all solution. For patients younger than 40 years, repair of type 2 SLAP tears that do not directly affect the biceps anchor (i.

Spatial interplay patterns of cancer nuclei and tumor-infiltrating lymphocytes (TILs) predict clinical benefit for immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) show prominent clinical activity across multiple advanced tumors. However, less than half of patients respond even after molecule-based selection. Thus, improved biomarkers are required.

Computational Analysis of Routine Biopsies Improves Diagnosis and Prediction of Cardiac Allograft Vasculopathy.

Background: Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality for heart transplant recipients. Although clinical risk factors for CAV have been established, no personalized prognostic test exists to confidently identify patients at high versus low risk of developing aggressive CAV. This investigation aimed to leverage computational methods for analyzing digital pathology images from routine endomyocardial biopsies (EMBs) to develop a precision medicine tool for predicting CAV years before overt clinical presentation.

Editorial Commentary: Interposition Graft Bridging Reconstruction: Good Mid-Term Outcomes for Massive Irreparable Rotator Cuff Tears.

Massive irreparable rotator cuff tears without glenohumeral arthritis are a common cause of shoulder pain and disability. Many surgical treatment options have been proposed, including debridement, partial repair, tendon transfer, superior capsule reconstruction, balloon spacer placement, bursal acromial reconstruction, and reverse shoulder arthroplasty. Interposition graft bridging reconstruction, as evidenced by the mid-term results of the current study, may also be considered, at least for now.

Rehabilitation Using a Systematic and Holistic Approach for the Injured Athlete Returning to Sport.

The purpose of this article is to identify gold standards of care for return to sport following athletic injury, investigate overlooked aspects of return to sport rehabilitation, and provide expert opinion regarding current practices. The article was written by performing a literature review, then providing editorial expert opinion regarding current standards of return to sport. We concluded, through literature review and expert consensus, that a three-pronged approach to return to sport is recommended for therapists.

Rehabilitation Using Acute Dry Needling for Injured Athletes Returning to Sport and Improving Performance.

Dry needling is most commonly used in the subacute and chronic phases of an injury; therefore, it is imperative to understand the use of dry needling in the acute phases of an injury. There are four main reasons to use dry needling during the acute phase of injury: to relieve pain, decrease edema, increase range of motion and flexibility, and increase strength and power. Dry needling can be used pregame, postgame, during half time or an intermission, or following an injury.