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Objective To determine the frequency and accuracy of diffusion restriction (DR) of the retina and/or optic nerve (ON) detection on standard brain magnetic resonance diffusion-weighted imaging (DWI-MRI) in patients presenting with acute non-arteritic central retinal artery occlusion (CRAO). Methods This is a retrospective case-control study that includes all consecutive patients presenting to our tertiary academic center from 2013-2021 with acute non-arteritic CRAO (cases) or acute ischemic stroke syndrome (controls, age and gender-matched) that had brain MRI performed within 14 days from symptom onset. Two neurology residents (junior and senior), a vascular neurologist, and two neuroradiologists, blinded to the site of CRAO, independently reviewed the brain MRIs to assess for the presence of retina and ON DR. The consensus agreement between the two neuroradiologists was used to perform sensitivity and specificity analyses and calculate inter-rater reliability (prevalence-adjusted bias-adjusted kappa coefficient). Results A total of 128 patients with acute non-arteritic CRAO (mean (SD) age 69 (14) years; 50% female; median time from CRAO to DW-MRI 2 days (IQR 1-5)) and 128 age and gender-matched controls with acute cerebral ischemia were included. After the neuroradiologist consensus, DR was correctly identified in the retina or ON in 51/128 (39.8%) CRAO cases, retina alone 27.3%, ON alone 24.2%, and both retina and ON 11.7%, with almost perfect neuroradiologists’ inter-rater reliability for retina (K = 0.91) and ON (K = 0.83). Among controls, the retina DR was identified in 1/128 (0.8%) and ON DR in 5/128 (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value were 28.1%, 99.2%, 97.3%, and 58.0% for retina DR, and 27.3%, 96.1%, 87.5%, and 56.9% for ON DR. Conclusions Though experienced neuroradiologists identified retina and ON DR with excellent inter-rater reliability, these are infrequent findings in real world CRAO practice, with excellent specificity but limited sensitivity. Prospective studies with larger cohort of patients, optimization of standardized orbit DWI-MRI protocols are needed to facilitate a more accurate and reliable identification of retina and ON DR in acute CRAO.

ABSTRACTBackgroundAdenovirus (ADV) infection can lead to significant morbidity and mortality in immunocompromised patients, particularly in those with hematopoietic stem cells or solid organ transplants. The incidence of ADV infection in kidney transplant (KT) is not well‐defined as ADV is often asymptomatic and not routinely checked.MethodsThis retrospective case‐series study included KT and simultaneous pancreas‐KT (SPKT) recipients from January 1, 2008, to January 31, 2024, across three Mayo Clinic sites (Arizona, Florida, and Minnesota) with symptomatic adenovirus polymerase chain reaction cases. The primary outcomes were allograft function at various intervals post‐ADV infection, allograft, and patient survival.ResultsWe report one of the largest multi‐site case series regarding outcomes of ADV in KT with 17 patients. The median time to ADV infection was 30 weeks (5–74). Five patients (29%) developed disseminated infection. Nine patients (53%) of the entire cohort experienced graft loss within a median of 35 (4–168) weeks, with four (44%) of graft loss attributed to ADV. Nine patients (53%) developed rejections post‐ADV infection with a median of 4 (2–8) weeks after resolution. One patient died from acute hypoxic respiratory failure from ADV infection.ConclusionADV should be considered in KT/SPKT patients with renal dysfunction, hematuria, and with or without fever. Despite the low mortality rate, there is a significant risk of graft loss and rejection after ADV infection. It is crucial to screen for ADV and develop intervention strategies for treatment. Further multicenter studies are needed to better define, stage, and manage ADV infection. image

BACKGROUND Cutaneous lichen planus (LP) is a recalcitrant, difficult-to-treat, inflammatory skin disease characterized by pruritic, flat-topped, violaceous papules on the skin. Baricitinib is an oral Janus kinase (JAK) 1/2 inhibitor that interrupts the signaling pathway of IFN-γ, a cytokine implicated in the pathogenesis of LP. METHODS In this phase II trial, 12 patients with cutaneous LP received 2 mg daily baricitinib for 16 weeks, accompanied by in-depth spatial, single-cell, and bulk transcriptomic profiling of pre- and posttreatment samples. RESULTS An early and sustained clinical response was seen, with 83.3% of patients responsive at week 16. Our molecular data identified a unique, oligoclonal IFN-γ, CD8 + , and CXCL13 + cytotoxic T cell population in LP skin and demonstrated a rapid decrease in IFN signature within 2 weeks of treatment, most prominently in the basal layer of the epidermis. CONCLUSION This study demonstrates the efficacy and molecular mechanisms of JAK inhibition in LP. TRIAL REGISTRATION NCT05188521 FUNDING Eli Lilly, Appignani Benefactor Funds, 5P30AR075043, Mayo Clinic Clinical Trials Stimulus Funds.

The hierarchical organization of the connective tissue, more specifically, the musculoskeletal soft tissue, has been extensively studied. With advancements in experimental methodology, investigation of the structure–function relationship has provided more insight into how the mechanical integrity of the tissue is created. Such information is essential in the linking the macroscopic loading environment of the tissue to the microscopic level of the tissue to be experienced by the cell. The flexibility and elastic modulus of gross connective tissue, the fascicle, the fiber and then the collagen molecule are compared based on the data available in the literature.

Neuropathic pain is a debilitating chronic condition that lacks effective treatment. The role of cytokine- and chemokine-mediated neuroinflammation in its pathogenesis has been well documented. Follistatin (FST) is a secreted protein known to antagonize the biological activity of cytokines in the transforming growth factor–β (TGF-β) superfamily. The involvement of FST in neuropathic pain and the underlying mechanism remain largely unknown. Here, we report that FST was up-regulated in A-fiber sensory neurons after spinal nerve ligation (SNL) in mice. Inhibition or deletion of FST alleviated neuropathic pain and reduced the nociceptive neuron hyperexcitability induced by SNL. Conversely, intrathecal or intraplantar injection of recombinant FST, or overexpression of FST in the dorsal root ganglion (DRG) neurons, induced pain hypersensitivity. Furthermore, exogenous FST increased neuronal excitability in nociceptive neurons. The biolayer interferometry (BLI) assay and coimmunoprecipitation (co-IP) demonstrated direct binding of FST to the insulin-like growth factor–1 receptor (IGF1R), and IGF1R inhibition reduced FST-induced activation of extracellular signal–regulated kinase (ERK) and protein kinase B (AKT), as well as neuronal hyperexcitability. Further co-IP analysis revealed that the N-terminal domain of FST exhibits the highest affinity for IGF1R, and blocking this interaction with a peptide derived from FST attenuated Nav1.7-mediated neuronal hyperexcitability and neuropathic pain after SNL. In addition, FST enhanced neuronal excitability in human DRG neurons through IGF1R. Collectively, our findings suggest that FST, released from A-fiber neurons, enhances Nav1.7-mediated hyperexcitability of nociceptive neurons by binding to IGF1R, making it a potential target for neuropathic pain treatment.

Introduction Telestroke enables timely and remote evaluation of patients with acute stroke syndromes. However, stroke mimics represent more than 30% of this population. Given the resources required for the management of suspected acute ischemic stroke, several scales have been developed to help identify stroke mimics. Our objective was to externally validate four mimic scales (Khan Score (KS), TeleStroke Mimic Score (TS), simplified FABS (sFABS), and FABS) in a large, academic telestroke network. Methods This is a retrospective, Institutional Review Board-exempt study of all patients who presented with suspected acute stroke syndromes and underwent video evaluation between 2019 and 2020 at a large academic telestroke network. Detailed chart review was conducted to extract both the variables needed to apply the mimic scales, the final diagnosis confirmed by final imaging, and discharge diagnosis (cerebral ischemic vs stroke mimic). Overall score performance was assessed by calculating the area under curve (AUC). Youden cutpoint was established for each scale and used to calculate sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy. Results A total of 1043 patients were included in the final analysis. Final diagnosis of cerebral ischemia was made in 63.5% of all patients, and stroke mimic was diagnosed in 381 patients (36.5%). To predict stroke mimic, TS had the highest AUC (68.3), sensitivity (99.2%), and NPV (77.3%); KS had the highest accuracy (67.5%); FABS had the highest specificity (55.1%), and PPV (72.5%). Conclusions While each scale offers unique strengths, none was able to identify stroke mimics effectively enough to confidently apply in clinical practice. There remains a need for significant clinical judgment to determine the likelihood of stroke mimic at presentation.

Background Endovascular treatment with the woven endobridge (WEB) device has been widely utilized for managing intracranial aneurysms. However, predicting the probability of achieving adequate occlusion (Raymond–Roy classification 1 or 2) remains challenging. Objective Our study sought to develop and validate a predictive calculator for adequate occlusion using the WEB device via data from a large multi-institutional retrospective cohort. Methods We used data from the WorldWide WEB Consortium, encompassing 356 patients from 30 centers across North America, South America, and Europe. Bivariate and multivariate regression analyses were performed on a variety of demographic and clinical factors, from which predictive factors were selected. Calibration and validation were conducted, with variance inflation factor (VIF) parameters checked for collinearity. Results A total of 356 patients were included: 124 (34.8%) were male, 108 (30.3%) were elderly (≥65 years), and 118 (33.1%) were current smokers. Mean maximum aneurysm diameter was 7.09 mm (SD 2.71), with 112 (31.5%) having a daughter sac. In the multivariate regression, increasing aneurysm neck size (OR 0.706 [95% CI: 0.535–0.929], p = 0.13) and partial aneurysm thrombosis (OR 0.135 [95% CI: 0.024–0.681], p = 0.016) were found to be the only statistically significant variables associated with poorer likelihood of achieving occlusion. The predictive calculator shows a c-statistic of 0.744. Hosmer–Lemeshow goodness-of-fit test indicated a satisfactory model fit with a p-value of 0.431. The calculator is available at: https://neurodx.shinyapps.io/WEBDEVICE/ . Conclusion The predictive calculator offers a substantial contribution to the clinical toolkit for estimating the likelihood of adequate intracranial aneurysm occlusion by WEB device embolization.

Background: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. Methods: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. Results: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5–6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. Conclusions: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget’s disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org .