Neuroinvasive West Nile Virus Infection in Immunosuppressed and Immunocompetent Adults.

Importance: West Nile virus (WNV) is the leading cause of human arboviral disease in the US, peaking during summer. The incidence of WNV, including its neuroinvasive form (NWNV), is increasing, largely due to the expanding distribution of its vector, the Culex mosquito, and climatic changes causing heavy monsoon rains. However, the distinct characteristics and outcomes of NWNV in individuals who are immunosuppressed (IS) and individuals who are not IS remain underexplored. Objective: To describe and compare clinical and radiographic features, treatment responses, and outcomes of NWNV infection in individuals who are IS and those who are not IS. Design, Setting, and Participants: This retrospective cohort study used data from the Mayo Clinic Hospital system collected from July 2006 to December 2021. Participants were adult patients (age ≥18 years) with established diagnosis of NWNV infection. Data were analyzed from May 12, 2020, to July 20, 2023. Exposure: Immunosuppresion. Main Outcomes and Measures: Outcomes of interest were clinical and radiographic features and 90-day mortality among patients with and without IS. Results: Of 115 participants with NWNV infection (mean [SD] age, 64 [16] years; 75 [66%] male) enrolled, 72 (63%) were not IS and 43 (37%) were IS. Neurologic manifestations were meningoencephalitis (98 patients [85%]), encephalitis (10 patients [9%]), and myeloradiculitis (7 patients [6%]). Patients without IS, compared with those with IS, more frequently reported headache (45 patients [63%] vs 18 patients [42%]) and myalgias (32 patients [44%] vs 9 patients [21%]). In contrast, patients with IS, compared with those without, had higher rates of altered mental status (33 patients [77%] vs 41 patients [57%]) and myoclonus (8 patients [19%] vs 8 patients [4%]). Magnetic resonance imaging revealed more frequent thalamic T2 fluid-attenuated inversion recovery hyperintensities in individuals with IS than those without (4 patients [11%] vs 0 patients). Individuals with IS had more severe disease requiring higher rates of intensive care unit admission (26 patients [61%] vs 24 patients [33%]) and mechanical ventilation (24 patients [56%] vs 22 patients [31%]). The 90-day all-cause mortality rate was higher in the patients with IS compared with patients without IS (12 patients [28%] vs 5 patients [7%]), and this difference in mortality persisted after adjusting for Glasgow Coma Scale score (adjusted hazard ratio, 2.22; 95% CI, 1.07-4.27; P = .03). Individuals with IS were more likely to receive intravenous immunoglobulin than individuals without IS (12 individuals [17%] vs 24 individuals [56%]), but its use was not associated with survival (hazard ratio, 1.24; 95% CI, 0.50-3.09; P = .64). Conclusions and Relevance: In this cohort study of individuals with NWNV infection, individuals with IS had a higher risk of disease complications and poor outcomes than individuals without IS, highlighting the need for innovative and effective therapies to improve outcomes in this high-risk population.

Topical Ruxolitinib in the Treatment of Necrobiosis Lipoidica: A Prospective, Open-Label Study.

Necrobiosis lipoidica (NL) is a rare granulomatous disease. There are few effective treatments for NL. We sought to investigate the efficacy and safety of the Jak1/2 inhibitor, ruxolitnib, in the treatment of NL and identify the biomarkers associated with the disease and treatment response. We conducted an open-label, phase 2 study of ruxolitinib in 12 patients with NL. We performed transcriptomic analysis of tissue samples before and after treatment. At week 12, the mean NL lesion score decreased by 58.2% (SD = 28.7%, P = .003). Transcriptomic analysis demonstrated enrichment of type I and type II IFN pathways in baseline disease. Weighted gene coexpression network analysis demonstrated post-treatment changes in IFN pathways with key hub genes IFNG and signal transducer and activator of transcription 1 gene STAT1. Limitations include small sample size and a study group limited to patients with <10% body surface area. In conclusion, ruxolitinib is an effective treatment for NL and targets the key pathogenic mediators of the disease.

Pulmonary Pathology Society Survey on Practice Approaches in the Histologic Diagnosis of Fibrotic Interstitial Lung Disease: Consensus and Opportunities.

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.

Prehospital stroke scales outperform National Institutes of Health Stroke Scale in predicting large vessel occlusion in a large academic telestroke network.

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.

Association of Primary Care Risk Mitigation Visits and Nonelective Emergency Department Visits in Patients Using Long-term Opioid Therapy.

Objective: To determine risk factors for nonelective emergency department visits (NEDVs) and whether primary care visits incorporating risk mitigation tools prevented NEDVs among patients using long-term opioid therapy (LOT). Patients and Methods: We retrospectively searched the electronic health records at Mayo Clinic primary care outpatient practices in Arizona and Florida in all of 2018 and 2019 for the records of individual adult patients using LOT. Patient and clinician demographic characteristics and patient risk factors were compared between patients with and without risk mitigation visits. Univariate and multivariable logistic regression was used to determine risk factors for NEDVs. Results: Among 457 patients using LOT identified during the study period, most were women (n=266, 58.2%), and the median age was 69 years. Long-term opioid therapy risk mitigation visits were performed equally by family medicine and internal medicine clinicians and by a significantly higher proportion of Florida clinicians than Arizona clinicians (87.0% vs 70.5%; P<.001). Older age, falls, and mental health care utilization all increased the risk of NEDVs. Risk mitigation visits were protective against NEDVs (odds ratio, 0.56; 95% CI, 0.35-0.89; P=.01) after adjustment for older age, falls, and mental health care utilization. Conclusion: Risk mitigation visits are effective in preventing NEDVs, and all patients using LOT should have such visits when possible.

Outcomes of asymptomatic histologic pyelonephritis of kidney transplant.

BACKGROUND: Urinary 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. METHODS: The 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. RESULTS: The 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. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.

Semi-supervised exercise training program more effective for individuals with postural orthostatic tachycardia syndrome in randomized controlled trial.

PURPOSE: Exercise like any medication requires the correct dose; to be effective the appropriate frequency, duration, and intensity are necessary. This study aimed to assess if a semi-supervised exercise training (ET) program would be more effective at improving aerobic fitness (VO2PEAK), exercise tolerance, and symptoms in individuals with postural orthostatic tachycardia syndrome (POTS) compared to the standard of care (SOC). METHODS: Subjects were randomized to either the ET or SOC groups (n 26 vs. 23; age 33 ± 11 vs. 37 ± 10 years; VO2PEAK 66 ± 15 vs. 62 ± 15% predicted, ET vs. SOC respectively, p > 0.05). Composite Autonomic Symptom Score (COMPASS 31), 10 min stand test, and cardiopulmonary exercise test were performed at baseline and following 12 weeks. The ET group received an exercise consultation and eight semi-supervised in-person or virtual exercise sessions. RESULTS: The ET group demonstrated a greater improvement in VO2PEAK, higher or longer tolerance for baseline peak workload, and more often had a delayed symptom onset with exercise than the SOC group (ΔVO2PEAK 3.4 vs. - 0.2 mL/min/kg, p < 0.0001, ΔWorkload 19 ± 17 vs. 0 ± 10 W; Workload time 63 ± 29 vs. 22 ± 30 s; onset-delay 80% vs. 30%, p < 0.05). Individuals in the ET group reported a significant improvement in orthostatic intolerance domain score (p = 0.02), but there was not a significant difference in the improvement in total COMPASS score (- 11.38 vs. - 6.49, p = 0.09). CONCLUSION: Exercise training was more effective with greater improvements in aerobic fitness, orthostatic symptoms, and exercise tolerance for individuals with POTS when intensity and progression were personalized and delivered with minimal supervision compared to the SOC.

Characterization of Blood-borne Pathogen Exposures During Dermatologic Procedures: The Mayo Clinic Experience.

Dermatologists are at risk for blood-borne pathogen (BBP) exposures. We conducted a retrospective review of incidence reports to identify the incidence of BBP exposures in dermatologic procedures. Secondary aims included identification of the type of exposure, type of procedure associated with each exposure, anatomic locations of exposures, and instruments involved in each exposure. Data were obtained at 3 Mayo Clinic sites in Scottsdale, Arizona; Jacksonville Florida; and Rochester, Minnesota, from 2010 to 2021. Two hundred twenty-two exposures were identified over an 11-year period. Results indicated that quality improvement measures should focus on training all dermatologic staff to reduce BBP exposures.

The impact of resilience on headache disability as measured by the Migraine Disability Assessment (MIDAS).

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.

Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients.

Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS-MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10-6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD had poor agreement, with high rates of PET-CT negativity in MRD-positive patients. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the ability to measure deeper and sustainable responses distinguishes patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.

Clinical Outcomes of Stereotactic Radiosurgery-Related Radiation Necrosis in Patients with Intracranial Metastasis from Melanoma.

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.

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

BACKGROUND: Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients. METHODS: Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors. RESULTS: There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated. CONCLUSION: eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

Is Continued Perioperative Antithrombotic Therapy Safe When Performing Open Tracheostomy?

OBJECTIVES: To date, there are no specific guidelines on antithrombotic therapy (ATT) management, which includes both anticoagulation and antiplatelet medications, for open tracheostomy. The objective of this study was to evaluate whether the use of perioperative antithrombotic medication during open tracheostomy influences the incidence of perioperative or postoperative complications. METHODS: A retrospective review was conducted of all patients who underwent open tracheostomies at a tertiary care medical center from January 2015 to December 2019. Charts were reviewed for demographics, comorbidities, indication for tracheostomy, ATT use, operative details, and complications. RESULTS: A total of 217 tracheostomies were evaluated for this study, of which 148 (68.2%) were not on ATT and 69 (31.8%) were on ATT during surgery. No significant difference was observed based on ATT status in perioperative bleeding (P = .983), postoperative bleeding (P = .24), or median days to decannulation (P = .5986). ATT patients were 2.67 times more likely to experience 30-day mortality than those non-ATT patients (P = .035). There was only one death due to hemorrhage in the ATT group. This was unrelated to the tracheostomy. This compares to 2 hemorrhage-related deaths in those not on ATT. CONCLUSION: There was no significant difference in perioperative or postoperative bleeding based on ATT use. Patients on ATT were significantly more likely to experience 30-day mortality, however only one death was due to hemorrhage in the ATT group and was unrelated to tracheostomy. Therefore, continued perioperative ATT use appears to be safe when performing open tracheostomy. LEVEL OF EVIDENCE: 4.

Evaluation of a Novel Wellness Curriculum on Medical Student Wellbeing and Engagement Demonstrates a Need for Student-Driven Wellness Programming.

PROBLEM: Medical training is stressful and has well-established implications for student wellbeing. Despite widespread efforts to reduce student burnout through wellness programming in medical schools, there is a paucity of literature examining students' perception of wellness and engagement with these programs. As such, we sought to evaluate: 1) medical students' level of engagement with a multifaceted wellness curriculum, 2) factors students perceived as important to wellbeing, and 3) associations with longitudinal measures of wellbeing and perceived stress. Intervention: A multipronged wellness curriculum was instituted at Mayo Clinic Alix School of Medicine-AZ (MCASOM-AZ) in 2017. This includes mental health services, curriculum-embedded seminars, wellness committee (composed of students, faculty, and administration) driven programming, and student proposed wellness activities that are reviewed and funded by the committee. The authors invited students at our institution to complete questionnaires at three timepoints during the 2018-2019 academic year. Questionnaires asked participants to rank eight factors from least to most important to their overall wellbeing. Participants self-reported their participation in each prong of the wellness curriculum and ranked the impact of each on their overall wellbeing. Their wellbeing and perceived stress were measured at each timepoint using validated psychological instruments. Context: As MCASOM-AZ opened in 2017, the student body at the time of study consisted of first- and second-year medical students. All students had the opportunity to engage with all aspects of the wellness curriculum and participate in this study, however participation was elective and all responses were anonymous. Of the MCASOM-AZ student body comprised of 100 students, 58 consented to participate in the study, 41.4% of which were Year 1 and 58.6% of which were Year 2 students. Participant age and gender were collected and were representative of the larger student body. Impact: Students engaged most with student-initiated wellness. They perceived unscheduled time as most impactful to their overall wellbeing with student-initiated activities as second-most impactful. Students with higher perceived stress were more likely than others to use mental health resources, which otherwise ranked lower in importance. Ranking academic performance as important to wellbeing was associated with higher wellbeing. There was no difference in wellbeing between students who participated in the wellness curriculum and those who did not. However, overall student wellbeing increased over the course of the year while perceived stress decreased. Lessons Learned: Medical school programs may benefit from allowing students to direct or contribute to the design of their own wellness curriculum. Additionally, medical education should work toward creating a more supportive learning environment with improved flexibility in order to better meet students' individual needs without compromising their education. Despite having low utilization rates overall, mental health resources remain an important aspect of student support services as they are used by students under greater amounts of perceived stress than their peers.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2021.2004415 .