Butterfield, Richard

Abstract BACKGROUND Leptomeningeal disease (LMD) carries poor prognosis with an average survival of 3-6 months after diagnosis. Ommaya reservoirs (OR) are an accessible alternative to serial lumbar punctures for delivery of intrathecal chemotherapy (IC) and disease monitoring but are not widely used. Intraventricular administration of chemotherapy may be associated with superior efficacy and improved patient comfort. The purpose of this study was to assess safety and efficacy of IC and disease monitoring via OR in routine clinical practice. METHODS Patients who received at least one administration of IC via OR for LMD between 2017 and 2022 were included. Demographics, treatment type, complications and outcomes were recorded. RESULTS We identified 22 patients (17 females, 5 males) with mean age 50.9 ± 14.8 years. The primary tumors were: breast (12), leukemia (3), ovarian carcinoma (3), CNS lymphoma (1), urothelial carcinoma (1), spinal melanocytoma (1), and high-grade glioma (1). A total of 208 OR injections were performed [median was 9 OR injections per patient, interquartile range (IQR) (5, 13)]. Five patients (23%) experienced mild adverse events of grade 2 or lower by Common Terminology Criteria for Adverse Events. Overall risk of adverse event from injection was 3.4% (7/208). Eight patients (36.3%) converted into negative CSF cytology (median 1 month following first injection). Eighteen patients (82%) had clinical or radiological progression of their LMD (median 2 months following first injection). Eleven patients (50%) died of their LMD during follow-up. Median OS and PFS from the first injection were 5.3 months [95% CI 4.8-NE (not estimable)] and 4.3 months [95% CI 1.8-16.0], respectively. CONCLUSION Use of OR in routine clinical practice is a safe and feasible option and should be strongly considered for treatment and monitoring of patients with LMD. The median OS in our cohort is comparable to prior published series.

Introduction Prehospital telestroke evaluations may improve stroke triage compared to paramedic-applied large vessel occlusion scales, but ambulance-based video National Institutes of Health Stroke Scale assessments are challenging. The accuracy of telestroke-administered large vessel occlusion scales has not been investigated, so we sought to evaluate this further. Methods This retrospective study included all in-hospital telestroke encounters in a large academic telestroke network from 2019 to 2020. We retrospectively calculated seven large vessel occlusion scales using the in-hospital telestroke National Institutes of Health Stroke Scale (Rapid Arterial oCclusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Field Assessment Stroke Triage for Emergency Destination, 3-Item Stroke Scale, Prehospital Acute Stroke Severity, Vision-Aphasia-Neglect, and Gaze-Face-Arm-Speech-Time). Diagnostic performance was assessed via sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio, negative likelihood ratio, and accuracy using established scale thresholds. These results were compared to the National Institutes of Health Stroke Scale at thresholds of 6, 8, and 10. The area under curve was calculated using c-statistics by treating scales as continuous variables. Results A total of 625 patients were included; 111 (17.8%) patients had an anterior large vessel occlusion, 118 (18.9%) patients had any large vessel occlusion, and 182 (29.1%) patients had stroke mimic diagnosis. The mean age (SD) was 67.9 (15.9), 48.3% were female, and 93.4% were white. The Mean National Institutes of Health Stroke Scale (SD) was 14.9 (8.4) for patients with anterior large vessel occlusion, 4.7 (5.0) for patients with non-large vessel occlusion ischemic stroke, and 4.4 (5.8) for stroke mimic ( p < 0.001). Compared to the National Institutes of Health Stroke Scale, Field Assessment Stroke Triage for Emergency Destination, and Rapid Arterial oCclusion Evaluation scales demonstrated higher accuracy and area under curve for large vessel occlusion detection. Discussion Both the Field Assessment Stroke Triage for Emergency Destination and Rapid Arterial oCclusion Evaluation scales outperformed the National Institutes of Health Stroke Scale for large vessel occlusion detection in patients evaluated by in-hospital telestroke. These scales may be valid alternatives to the National Institutes of Health Stroke Scale examination in this setting.

AbstractBackgroundPrevious literature on cutaneous squamous cell carcinoma (cSCC) suggests that the incidence, rate of metastasis, and tumour severity of cSCC are higher in immunosuppressed patients than in immunocompetent patients. However, current literature lacks an extensive comparison of cSCC clinical characteristics and outcomes in immunosuppressed patients.ObjectivesWe compared cSCC tumour characteristics and disease‐related outcomes to help guide the clinical management of immunosuppressed patients.MethodsWe conducted a retrospective review of histopathologic and clinical data from 935 cSCC cases (19.5% immunosuppressed) from the Mayo Clinic.ResultsImmunosuppression was associated with younger age (69.3 vs. 74.8 years old, p < 0.0001), male gender (78.6% vs. 67.2%, p = 0.003), and higher grade cSCC tumour characterized by moderate or poor differentiation (25.7% vs. 15.8%, p = 0.009; 9.2% vs. 7.2%, p = 0.009, respectively). No significant differences were found in other tumour characteristics, including clinical tumour dimension, Brigham and Women's Hospital tumour staging or cumulative risk of metastasis and recurrence. Immunosuppressed patients had an increased risk of disease‐specific death on univariate analysis (hazard ratio [HR] [95% confidence interval, CI] 2.05 [1.13–3.74], p = 0.0128). Overall survival in the immunosuppressed population was worse (adjusted HR [95% CI] 1.83 [1.42–2.35], p < 0.001) and, notably, solid organ transplant recipients had the lowest overall survival when stratifying immunosuppressed patients by immunosuppression type (HR [95% CI] 1.62 [1.17–2.24], p < 0.0001).ConclusionsIn our study, immunosuppression status was predictive of poor differentiation of tumours and a reduction in overall and cSCC‐specific survival. Current staging systems for cSCC do not include immunosuppression as a risk factor and incorporating immune status may be beneficial for accurate risk stratification.

AbstractBackgroundUrinary Tract Infections are the most common post‐transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy.MethodsThe study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant.ResultsThe mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3–2.7, diabetes mellitus (OR 2.479, 1.687–3.645), and deceased donation (OR 1.69, 1.098–2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06–3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36–6.02) and a trend toward higher rejection risk.ConclusionAsymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

AbstractBackgroundPrimary cutaneous B‐cell lymphoma (PCBCL) is a group of B‐cell lymphomas of the skin containing primary cutaneous follicle centre lymphoma (PCFCL) and marginal zone B‐cell lymphoma/lymphoproliferative disorder (PCMZL), which are indolent, and diffuse large B‐cell lymphoma, leg type (PCDLBCL‐LT), which is aggressive.ObjectivesTo evaluate treatment outcomes between PCBCL subtypes after treatment with rituximab and to compare the efficacy of intralesional against systemic rituximab in indolent subtypes.MethodsA search for patients diagnosed with PCBCL and treated with rituximab (systemic or intralesional) across all Mayo Clinic sites was performed, yielding 39 patients.ResultsEight patients had PCFCL (six treated intralesionally and two systemically), 11 had PCMZL (four intralesional, eight systemic with one dual‐treated) and 20 had PCDLBCL‐LT (all systemic). The average age at diagnosis was 62.1 years (SD = 15.1), with average follow‐up of 1852.6 days (SD = 1473.2). 69.2% of all patients treated with any form of rituximab experienced a complete response (100% PCFCL, 81.8% PCMZL and 50% PCDLBCL‐LT). When comparing all three subtypes, a significant difference was seen in overall treatment response (p = 0.022), and progressive disease rates (p = 0.015), but not in retreatment with rituximab (p = 0.440), time to retreatment (p = 0.757), recurrence (p = 0.907) or survival (p = 0.093). In the indolent subtypes, no difference in overall treatment response (p = 1.000), progressive disease rates (p = 1.000), recurrence (p = 0.650), rituximab retreatment (p = 0.650) or time to retreatment (p = 0.724) was observed.ConclusionsThis study suggests that rituximab, as systemic therapy and intralesional therapy, is effective in the management of PCBCL, and that intralesional therapy should be considered before more aggressive therapy in indolent disease.

Context.— The pathologic diagnosis of usual interstitial pneumonia (UIP) remains a challenging area, and application of histologic UIP guidelines has proved difficult. Objective.— To understand current practice approaches by pulmonary pathologists for the histologic diagnosis of UIP and other fibrotic interstitial lung diseases (ILDs). Design.— The Pulmonary Pathology Society (PPS) ILD Working Group developed and sent a 5-part survey on fibrotic ILD electronically to the PPS membership. Results.— One hundred sixty-one completed surveys were analyzed. Of the respondents, 89% reported using published histologic features in clinical guidelines for idiopathic pulmonary fibrosis (IPF) in their pathologic diagnosis; however, there was variability in reporting terminology, quantity and quality of histologic features, and the use of guideline categorization. Respondents were very likely to have access to pulmonary pathology colleagues (79%), pulmonologists (98%), and radiologists (94%) to discuss cases. Half of respondents reported they may alter their pathologic diagnosis based on additional clinical and radiologic history if it is pertinent. Airway-centered fibrosis, granulomas, and types of inflammatory infiltrates were considered important, but there was poor agreement on how these features are defined. Conclusions.— There is significant consensus among the PPS membership on the importance of histologic guidelines/features of UIP. There are unmet needs for (1) consensus and standardization of diagnostic terminology and incorporation of recommended histopathologic categories from the clinical IPF guidelines into pathology reports, (2) agreement on how to incorporate into the report relevant clinical and radiographic information, and (3) defining the quantity and quality of features needed to suggest alternative diagnoses.

Abstract Objective Our objectives were to examine cross‐sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. Background Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache‐related disability as measured by the Migraine Disability Assessment (MIDAS). Methods We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS‐25), Patient Health Questionnaire‐9 (PHQ‐9), Generalized Anxiety Disorder‐7 (GAD‐7), and WHO‐5 Well‐Being Index. Results The CDRS‐25 score was negatively correlated with the total MIDAS ( r = −0.21, p = 0.009), GAD‐7 ( r = −0.56, p < 0.001), and PHQ‐9 scores ( r = −0.34, p < 0.001). Well‐being inversely correlated with disability ( r = −0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS‐25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS‐25 score did not significantly moderate the association between headache days and disability. Conclusion Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Background: Radiation necrosis (RN) is a clinically relevant complication of stereotactic radiosurgery (SRS) for intracranial metastasis (ICM) treatments. Radiation necrosis development is variable following SRS. It remains unclear if risk factors for and clinical outcomes following RN may be different for melanoma patients. We reviewed patients with ICM from metastatic melanoma to understand the potential impact of RN in this patient population. Methods: Patients who received SRS for ICM from melanoma at Mayo Clinic Arizona between 2013 and 2018 were retrospectively reviewed. Data collected included demographics, tumor characteristics, radiation parameters, prior surgical and systemic treatments, and patient outcomes. Radiation necrosis was diagnosed by clinical evaluation including brain magnetic resonance imaging (MRI) and, in some cases, tissue evaluation. Results: Radiation necrosis was diagnosed in 7 (27%) of 26 patients at 1.6 to 38 months following initial SRS. Almost 92% of all patients received systemic therapy and 35% had surgical resection prior to SRS. Patients with RN trended toward having larger ICM and a prior history of surgical resection, although statistical significance was not reached. Among patients with resection, those who developed RN had a longer period between surgery and SRS start (mean 44 vs 33 days). Clinical improvement following treatment for RN was noted in 2 (29%) patients. Conclusions: Radiation necrosis is relatively common following SRS for treatment of ICM from metastatic melanoma and clinical outcomes are poor. Further studies aimed at mitigating RN development and identifying novel approaches for treatment are warranted.

Introduction: Prehospital telestroke is increasingly utilized in mobile stroke units and telemedicine-enabled ambulances for acute ischemic stroke (AIS). While the NIHSS remains the standard for telestroke assessment, simpler scales have been validated to help paramedics recognize large vessel occlusion (LVO) strokes but have not been evaluated in a traditional telestroke network. We aimed to determine the accuracy of common LVO scales in a large academic telestroke practice. Methods: This retrospective study included all telestroke consults performed in a large academic telestroke network from 2019 to 2020. Patients were excluded if no NIHSS or vessel imaging was performed. We recorded presenting NIHSS, site of vessel occlusion, and discharge diagnosis. LVO was defined as an acute occlusion of the internal carotid artery and/or M1 middle cerebral artery. The NIHSS was used to calculate 7 LVO scales (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy using the established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables. Results: A total of 625 patients were included, 373/625 (59.7%) of which were diagnosed with AIS at discharge. LVO was identified in 78/625 (12.5%) patients. VAN was the most sensitive prehospital stroke scale (83.3%), whereas 3I-SS ≥ 4 was the most specific (95.2%). Both the RACE and FAST-ED scales demonstrated superior accuracy and AUC compared to the NIHSS (Table 1). Conclusions: To our knowledge, this is the first study assessing LVO scale accuracy in a large telestroke network. As use of prehospital telestroke grows, this study highlights several scales that may allow for faster prehospital triage decisions without sacrificing accuracy.