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Importance Use of modern neoadjuvant chemotherapy (NAC) regimens has markedly increased rates of pathologic complete response (pCR) in breast cancer, raising the question of whether surgical removal of the primary tumor is required for patients with pCR. For surgery to be omitted, one must be able to accurately predict pCR before surgery. Objective To investigate if adding post-NAC core needle biopsy of the tumor bed to trimodality imaging in patients who have clinical complete response (cCR) will predict pCR (resolution of both invasive disease and ductal carcinoma in situ) in 90% or more cases. Design, Setting, and Participants This was a phase 2, prospective, nonrandomized clinical trial. Patients were enrolled from August 2017 to June 2019. This is the final analysis, which was completed in December 2023. The setting included academic and community hospital center members of NRG (ie, the National Surgical Adjuvant Breast and Bowel Project, the Radiation Therapy Oncology Group, and the Gynecologic Oncology Group) in the US and Canada. Patients with operable (T1-T3, stage I-III) invasive ductal carcinoma who completed NAC and achieved cCR and radiological complete response (rCR) or near rCR by mammography (mass ≤1 cm and no malignant microcalcifications), ultrasound (mass ≤2 cm), and magnetic resonance imaging (no mass with rapid rise or washout kinetics). Interventions Patients underwent marker-directed stereotactic multiple-core needle biopsy of the tumor bed with marker placement before breast-conservation surgery. Main Outcomes and Measures End points were negative predictive value (NPV) and sensitivity of the biopsy. Results A total of 105 patients were enrolled with 101 evaluable (mean [SD] age, 52.8 [10.5] years); 77 patients (76.2%) were younger than 60 years, and all breast cancer subtypes were represented with 32 (31.7%) triple-negative breast cancer, 21 (20.8%) hormone receptor–positive/epidermal growth factor receptor 2 ( ERBB2 ; formerly HER2 )–negative ( ERBB2 −) breast cancer, and 46 (45.5%) ERBB2 -positive ( ERBB2 +) breast cancer. In 101 evaluable patients, 36 had residual disease at surgery (pCR = 64%). With imaging criteria, NPV of the biopsy was 78.3% (95% CI, 67.9%-86.6%), and the sensitivity of the biopsy was 50% (95% CI, 32.9%-67.1%). In an exploratory subset analysis, the NPV in patients with ERBB2 + breast cancer was 90% (95% CI, 76.3%-97.2%). On retrospective central review, 62 of 101 enrolled patients met imaging eligibility criteria. In this exploratory post hoc analysis, NPV in these patients was 86.8% (95% CI, 74.7%-94.5%). Conclusions and Relevance These findings do not support breast conservation treatment without surgery based on the study criteria for cCR and rCR/near rCR by trimodality imaging and negative tumor-bed biopsy. Strict adherence to imaging criteria may be required to achieve acceptable predictive values. TRIAL Registration ClinicalTrials.gov Identifier: NCT03188393

Introduction: Bone health optimization is a key component of the preoperative management of spine surgery patients, as poor bone quality increases the odds of mechanical complications. The present study aimed to achieve the following: (1) compare the relative efficacy of current osteoporosis medications in improving bone quality; (2) identify factors influencing treatment response in preoperative spine surgery patients. Methods: Patients treated at a single, multisite institution who received osteoporosis treatment were identified. Data were gathered on pre- and post-treatment lumbar spine Hounsfield Unit (HU) measurements, patient demographics, frailty scores (modified Frailty Index/mFI, risk analysis index/RAI), and pharmacologic treatment details. The primary outcome was a ≥7 point improvement in lumbar HU, and baseline and logistic regression models were utilized to identify factors associated with this improvement. Medications were grouped as anabolic (teriparatide, romosozumab) and antiresorptive (denosumab, alendronate) therapies. Results: A total of 267 patients were included (median age: 74 years; IQR [66–81]; 67.3% female), with 127 (47.6%) improving by ≥7 HU. The treatment agents used were alendronate (95), denosumab (113), romosozumab (31), and teriparatide (28). Univariable comparisons revealed significant differences across medication groups in age (p < 0.001), sex (p < 0.001), mFI (p < 0.001), RAI (p = 0.004), BMI (p < 0.001), pre-treatment HU (p = 0.022), and treatment duration (p < 0.001). The highest HU improvement rates (ΔHU ≥ 7) were observed in patients receiving the anabolic medications romosozumab (67.7%) and teriparatide (60.7%). Univariable logistic regression identified male sex (OR 0.54, p = 0.019), higher pre-treatment HU (OR 0.99, p = 0.006), and longer treatment duration (OR 0.97, p = 0.003) as factors associated with lower odds of HU improvement. Only romosozumab was associated with significantly higher odds of HU improvement relative to alendronate (OR 3.02, p = 0.012). In our multivariable analysis, male sex (OR 0.53, p = 0.028) and higher pre-treatment HU (OR 0.99, p = 0.002) remained significant predictors of HU improvement. However, medication type was not significant in the multivariable analysis. Conclusions: Our study highlights that male sex and higher pre-treatment HU were independently associated with lower odds of HU improvement, while medication type was not a significant predictor. Additionally, anabolic agents offered superior improvement relative to antiresorptive therapies.

ObjectiveThe objective is to provide evidence‐based and expert guidance for the screening, treatment, and management of lupus nephritis.MethodsThe Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation.ResultsWe present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus‐based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3–5 years for those achieving complete renal response.ConclusionThis guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

AbstractPurposeWhile several artificial intelligence (AI)‐assisted medical imaging applications are reported in the recent orthopaedic literature, comparison of the clinical efficacy and utility of these applications is currently lacking. The aim of this systematic review is to evaluate the effectiveness and reliability of AI applications in orthopaedic imaging, focusing on their impact on diagnostic accuracy, image segmentation and operational efficiency across various imaging modalities.MethodsBased on the PRISMA guidelines, a comprehensive literature search of PubMed, Cochrane and Scopus databases was performed, using combinations of keywords and MeSH descriptors ('AI', 'ML', 'deep learning', 'orthopaedic surgery' and 'imaging') from inception to March 2024. Included were studies published between September 2018 and February 2024, which evaluated machine learning (ML) model effectiveness in improving orthopaedic imaging. Studies with insufficient data regarding the output variable used to assess the reliability of the ML model, those applying deterministic algorithms, unrelated topics, protocol studies, and other systematic reviews were excluded from the final synthesis. The Joanna Briggs Institute (JBI) Critical Appraisal tool and the Risk Of Bias In Non‐randomised Studies‐of Interventions (ROBINS‐I) tool were applied for the assessment of bias among the included studies.ResultsThe 53 included studies reported the use of 11.990.643 images from several diagnostic instruments. A total of 39 studies reported details in terms of the Dice Similarity Coefficient (DSC), while both accuracy and sensitivity were documented across 15 studies. Precision was reported by 14, specificity by nine, and the F1 score by four of the included studies. Three studies applied the area under the curve (AUC) method to evaluate ML model performance. Among the studies included in the final synthesis, Convolutional Neural Networks (CNN) emerged as the most frequently applied category of ML models, present in 17 studies (32%).ConclusionThe systematic review highlights the diverse application of AI in orthopaedic imaging, demonstrating the capability of various machine learning models in accurately segmenting and analysing orthopaedic images. The results indicate that AI models achieve high performance metrics across different imaging modalities. However, the current body of literature lacks comprehensive statistical analysis and randomized controlled trials, underscoring the need for further research to validate these findings in clinical settings.Level of evidenceSystematic Review; Level of evidence IV.

EndMT has been reported to contribute to the pathogenesis of PAH. In this study, we aimed to determine the role of Ca 2+ signaling in the development of EndMT in human lung vascular endothelial cells. Our data suggest that TGF-β 1 requires store-operated Ca 2+ entry through STIM1/Orai channels to induce SNAI-mediated EndMT. For the first time, we demonstrated that TGF-β 1 -induced EndMT is a Ca 2+ -dependent event, whereas inhibition of STIM1/Orai interaction attenuated EndMT in response to TGF-β 1 .

Introduction: Online self-triage/symptom checkers are a relatively new e-Health modality. We aimed to evaluate the degree to which patient’s chosen symptom during the use of an online self-triage tool was congruent with that chosen by a nurse performing phone triage. Methods: Patient encounters from September 1, 2022, to September 30, 2023, were reviewed for patients who completed both online self-triage and a subsequent nursing phone triage within 24 hours. The symptoms chosen by the patient for their self-triage encounter and the symptoms chosen by the nurse during the subsequent nurse triage were reviewed. The symptoms chosen in these two triage encounters were then compared for congruency. A subset of our database was evaluated for congruency between the self-triage and the nurse phone triage endpoint recommendations. Results: There were 5,443 encounters meeting inclusion criteria to study for congruency between self-triage and nurse triage symptom choice. The range of time between self-triage and nurse triage ranged from 0 min to 1,439 min (23.9 hours) with a median of 23 minutes between self and nurse triage encounters. Symptom congruency between the two methods found 74.2% (4,038) to be completely congruent while 989 (18.2%) were somewhat congruent. Only 7.6% (416) had no apparent congruency. Out of 1,705 self and nurse triage dyads eligible for study for agreement between endpoint recommendations, 244 (14.3%) were under-triaged, 1,110 (65.1%) were triaged to the same level of care and 351 (20.6%) were over-triaged. Conclusion: Congruency between symptoms chosen by the patient for triage and nurse triage were highly congruent with only 7.6% of the sample showing no apparent congruency between the self-triage symptom and the nurse triage symptom. When compared to nurse triage, most self-triage endpoint recommendations were either triaged to the same level of care or were over-triaged to a higher level of care.

ABSTRACTThe incidence of ischemic cholangiopathy (IC) is expected to remain significant due to rising rates of transplants performed with livers donated after circulatory death (DCD), despite the use of machine perfusion. Absent established pharmacologic interventions against this progressive etiology of allograft dysfunction and failure, we describe the use of fenofibrate—a cheap and widely‐accessible peroxisome proliferator‐activated receptor agonist that downregulates bile acid production—to impede IC progression in 15 DCD liver recipients who were not responding to reactive, standard‐of‐care management. All patients were undergoing serial endoscopic retrograde cholangiopathy (ERC) to maintain biliary patency but demonstrated progressive cholestasis, with serum alkaline phosphatase (ALP) rising 70.3% over the 90 days preceding fenofibrate. Cholestasis improved in all patients after fenofibrate initiation, with a 63.9% reduction in mean ALP at 90 days, maintained at 270 days (p = 0.02) and 360 days (p = 0.06). ALP improvement was associated with reduced ERC frequency during and after fenofibrate treatment, and this improvement was independent of concurrent ERC or ursodeoxycholic acid use during fenofibrate treatment. In patients who stopped treatment, ALP increased. No fenofibrate‐associated adverse events were seen. These preliminary data support the further study of agents that downregulate bile acid production as a means of impeding IC in DCD livers.

Quantitative susceptibility mapping of iron deposition in sporadic cerebral cavernous malformation-related epilepsy Zhang S, Liu Y, Ma L, Yuan J, Wu C, Wang S. Epilepsia . 2025 Jan 13. doi: 10.1111/epi.18263 . Epub ahead of print. PMID: 39804066. Objective: To evaluate iron deposition patterns in patients with cerebral cavernous malformation-related epilepsy (CRE) using quantitative susceptibility mapping (QSM) for detailed analysis of iron distribution associated with a history of epilepsy and severity. Methods: This study is part of the Quantitative Susceptibility Biomarker and Brain Structural Property for Cerebral Cavernous Malformation-Related Epilepsy (CRESS) cohort, a prospective multicenter study. QSM was used to quantify iron deposition in patients with sporadic cerebral cavernous malformation (CCMs). Lesions were segmented into intralesional, perilesional, and extralesional areas, with mean susceptibility values calculated for each subregion and analyzed in relation to epilepsy severity and duration. Results: Among the 46 patients studied, those with a history of epilepsy had significantly higher iron deposition values in the perilesional ( P = .012) and extralesional areas ( P = .01), as well as a greater extent of iron deposition ( P < .001) compared to those without epilepsy. The extent of iron deposition effectively distinguished patients with and without epilepsy, with an area under the curve (AUC) of 0.901 (95% confidence interval [CI]: 0.816-0.985). Among patients with epilepsy, iron deposition in the extralesional area was positively correlated with the severity of epilepsy (r2 = 0.181, P = .043), and the extent of iron deposition was positively correlated with the duration of epilepsy (r2 = .214, P = .026). Significance: This study highlights QSM as a noninvasive tool for assessing iron deposition in CRE, identifying distinct subregional iron deposition patterns linked to epilepsy status and severity.