Trial Readiness of Cavernous Malformations With Symptomatic Hemorrhage, Part I: Event Rates and Clinical Outcome.

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.

Implementation Costs of Technology-Enhanced Transitional Palliative Care for Rural Caregivers.

OBJECTIVES: Compared to urban family caregivers (FCG), rural FCG experience greater burdens accessing coordinated care for their loved ones during and after hospitalization. The impact of technology-enhanced transitional palliative care (TPC) on caregiver outcomes is currently being evaluated in a randomized control trial. This study evaluates resource use and health system costs of this FCG-focused TPC intervention and potential Medicare reimbursement mechanisms. METHODS: Rural caregivers of hospitalized patients were randomized into an 8-week intervention consisting of video visits conducted by a registered nurse certified in palliative care, supplemented with phone calls and texts (n = 215), or attentional control. Labor costs were estimated for a registered nurse and compared to scenario analyses using a nurse practitioner or social worker wages. Medicare reimbursement scenarios included Transitional Care Management (TCM) and Chronic Care Management (CCM) CPT codes. RESULTS: In the base case, TPC cost was $395 per FCG facilitated by a registered nurse, compared to $337 and $585 if facilitated by a social worker or nurse practitioner, respectively. Mean Medicare reimbursement in the TCM-only scenario was $322 and $260 for high or moderate complexity patients, respectively. Reimbursement in the CCM only scenario was $348 and $274 for complex and non-complex patients, respectively. Reimbursement in the TCM+CCM scenario was $496 and $397, for high/complex and moderate/non-complex patients, respectively. CONCLUSION: TPC is a feasible, low cost and sustainable strategy to enhance FCG support in rural areas. Potential reimbursement mechanisms are available to offset the costs to the health system for providing transitional palliative care to caregivers of patients recently hospitalized.

Sural nerve biopsy utility by masked assessment of individual histologic preparations.

BACKGROUND AND AIMS: Comprehensive study of sural nerve biopsy utility based on individual histopathologic preparations is lacking. We aimed to quantify the value of different histologic preparations in diagnosis. METHODS: One hundred consecutive sural nerves were studied by standard histological preparations plus graded teased nerve fibers (GTNF), immunohistochemistry, and epoxy-semithin morphometry. Three examiners scored the individual preparations separately by a questionnaire of neuropathic and interstitial abnormalities, masked to the biopsy number, versus a gold-standard of all preparations. Multivariate modeling was utilized to determine best approach versus the gold-standard. RESULTS: Highest confidence (range 8-9 of 10) and inter-rater reliability (99%) for fiber abnormalities came from GTNF, and interstitial abnormalities from paraffin stains (range 7-8, 99%). Vasculitic neuropathy associated with GTNF axonal degeneration (moderate to severe 79%) with OR 3.8, 95% CI (1.001-14.7), p = .04, but not significantly with the other preparations. Clinicopathologic diagnoses associated with teased fiber abnormalities in chronic inflammatory demyelinating polyradiculoneuropathy, 80% (8/10); amyloidosis, 50% (1/2); adult-onset polyglucosan disease 100% (1/1). GTNF and paraffin stains significantly correlated with fiber density determined by morphometric analysis (GTNF: OR 9.9, p < .0001, paraffin: OR 3.8, p = .03). GTNF combined with paraffin sections had highest accuracy for clinicopathologic diagnoses and fiber density with 0.86 C-stat prediction versus morphometric analysis. Pathological results lead to initiation or changes of immunotherapy in 70% (35/50; initiation n = 22, reduction n = 9, escalation n = 4) with the remaining having alternative intervention or no change. INTERPRETATION: Nerve biopsy paraffin stains combined with GTNF have highest diagnostic utility, confidence, inter-rater reliability, improving accuracy for a pathologic diagnosis aiding treatment recommendations. Immunostains and epoxy preparations are also demonstrated useful supporting consensus guidelines. This study provides class II evidence for individual nerve preparation utility.

A 92 protein inflammation panel performed on sonicate fluid differentiates periprosthetic joint infection from non-infectious causes of arthroplasty failure.

Periprosthetic joint infection (PJI) is a major complication of total joint arthroplasty, typically necessitating surgical intervention and prolonged antimicrobial therapy. Currently, there is no perfect assay for PJI diagnosis. Proteomic profiling of sonicate fluid has the potential to differentiate PJI from non-infectious arthroplasty failure (NIAF) and possibly clinical subsets of PJI and/or NIAF. In this study, 200 sonicate fluid samples, including 90 from subjects with NIAF (23 aseptic loosening, 35 instability, 10 stiffness, five osteolysis, and 17 other) and 110 from subjects with PJI (40 Staphylococcus aureus, 40 Staphylococcus epidermidis, 10 Staphylococcus lugdunensis, 10 Streptococcus agalactiae, and 10 Enterococcus faecalis) were analyzed by proximity extension assay using the 92 protein Inflammation Panel from Olink Proteomics. Thirty-seven of the 92 proteins examined, including CCL20, OSM, EN-RAGE, IL8, and IL6, were differentially expressed in PJI versus NIAF sonicate fluid samples, with none of the 92 proteins differentially expressed between staphylococcal versus non-staphylococcal PJI, nor between the different types of NIAF studied. IL-17A and CCL11 were differentially expressed between PJI caused by different bacterial species, with IL-17A detected at higher levels in S. aureus compared to S. epidermidis and S. lugdunensis PJI, and CCL11 detected at higher levels in S. epidermidis compared to S. aureus and S. agalactiae PJI. Receiver operative characteristic curve analysis identified individual proteins and combinations of proteins that could differentiate PJI from NIAF. Overall, proteomic profiling using this small protein panel was able to differentiate between PJI and NIAF sonicate samples and provide a better understanding of the immune response during arthroplasty failure.

Utility of Carpal Tunnel Release and Ulnar Decompression in CMT1A and HNPP.

INTRODUCTION/AIMS: Carpal and cubital tunnel syndrome (CTS, CuTS) are common among patients with hereditary neuropathy with liability to pressure-palsies (HNPP) and Charcot-Marie-Tooth type 1A (CMT1A) and may impact quality of life. We aimed to evaluate the utility of nerve decompression surgeries in these patients. METHODS: Medical records were reviewed for patients with PMP22 mutations confirmed in Mayo Clinic laboratories from January 1999 to December 2020, who had CTS and CuTS and underwent surgical decompression. RESULTS: CTS occurred in 53.3% of HNPP and 11.5% of CMT1A, while CuTS was present in 43.3% of HNPP and 5.8% of CMT1A patients. CTS decompression occurred in 10-HNPP and 5-CMT1A patients, and CuTS decompression with/without transposition was performed in 5-HNPP and 1-CMT1A patients. In HNPP, electrodiagnostic studies identified median neuropathy at the wrist in 9/10 patients and ultrasound showed focal enlargements at the carpal and cubital tunnels. In CMT1A, median and ulnar sensory responses were all absent, and the nerves were diffusely enlarged. After CTS surgery, pain, sensory loss, and strength improved in 4/5 CMT1A, and 6/10 HNPP patients. Of clinical, electrophysiologic and ultrasound findings, only activity-provoked features significantly correlated with CTS surgical benefit in HNPP patients (odds ratio = 117.0:95% confidence interval, 1.94 > 999.99, p = 0.01). One CMT1A and one HNPP patient improved with CuTS surgery while 2 HNPP patients worsened. DISCUSSION: CTS symptom improvement post-surgery can be seen in CMT1A and (less frequent) in HNPP patients. CuTS surgery commonly worsened course in HNPP. Activity-provoked symptoms in HNPP best informed benefits from CTS surgery.

Does BMI Matter? A 10-Year Single Institutional Experience on 571 Bariatric Surgery Patients With BMI >50 kg/m 2.

INTRODUCTION: Patients undergoing bariatric surgery with body mass index (BMI) >50 kg/m 2 are at a higher risk of surgical morbidity when compared with less obese patients, however, there is limited data correlating surgical risk and efficacy with increasing BMI in patients with severe obesity. We hypothesize that regardless of the degree above 50 kg/m 2 their BMI, patients with severe obesity respond similarly to bariatric surgery. MATERIALS AND METHODS: We performed a retrospective analysis of patients with BMI >50 kg/m 2 who underwent biliopancreatic diversion with duodenal switch, Roux-en-Y gastric bypass, or sleeve gastrectomy at a single institution. Outcomes were compared in patients with a BMI between 50 and 60 kg/m 2 to patients with a BMI >60 kg/m 2 and included percent total weight loss as well as early and late complications. Statistical analyses were performed using logistic regression, univariate, and multivariate models. RESULTS: There were 571 patients with BMI >50 kg/m 2 who underwent bariatric surgery at our center, 170 (29.8%) had a BMI >60 kg/m 2 . Percent total weight loss was statistically significant between the BMI 50 and 60 kg/m 2 and BMI >60 kg/m 2 groups at 24 months ( P =0.047) but not at 60 months ( P =0.54). No significant difference was found in the incidence of early complications in a univariate ( P =0.46) or a multivariate ( P =0.06) analysis. The BMI >60 subgroup was associated with a higher rate of late complications in univariate analysis (heart rate=2.37; 1.03-5.47, P =0.04), but not in multivariate analysis ( P =0.78). CONCLUSIONS: Efficacy and complication rates of bariatric surgeries are similar in patients with BMI 50 to 60 kg/m 2 and >60 kg/m 2 , providing evidence supporting similar management of patients despite specific subgroups.

Cancer and immune-mediated necrotizing myopathy: a longitudinal referral case-controlled outcomes evaluation.

OBJECTIVES: To investigate immune-mediated necrotizing myopathy (IMNM) association with cancer and its clinical implications. METHODS: IMNM cases were identified 1 January 2000 to 31 December 2020 matching sex and age controls (4:1). RESULTS: A total of 152 patients with IMNM were identified and among serologically tested, 60% (83/140) were HMGCR-IgG+, 14% (20/140) were SRP-IgG+ and 26% (37/140) were seronegative. Cancer rates were not significantly different between serological subgroups; 18.1% (15/83) HMGCR-IgG+, 25% (5/20) SRP-IgG+ and 30% (11/37) seronegative (P = 0.34). Cancer screening was performed within 12 months from IMNM diagnosis in 88% (134/152) (whole-body CT plus FDG-PET CT in 53, CT alone in 72 and FDG-PET alone in 9). FDG-PET/CT was positive in 73% (25/34) of cancers. Increasing age was the only risk associated with cancer (P = 0.02). The odds of developing cancer at ±3 or ±5 years from IMNM diagnosis was not higher than controls (OR = 0.49; CI: 0.325-0.76). Lifetime IMNM diagnosis of cancer was less compared with controls (OR = 0.5 CI: 0.33-0.78, P = 0.002). Most patients responded to treatment (137/147, P < 0.001). Death and treatment response did not significantly differ between cancer [23% (8/34); 88% (29/33)] and non-cancer patients [19% (23/118); 92% (108/118)]. In total, 13% (20/152) of patients died during follow-up compared with 14% (41/290) of medicine and 16% (46/290) of neurology controls (P = 0.8). Seropositives had greater life expectancy than seronegatives (P = 0.01). CONCLUSIONS: Greater cancer risk is not observed in IMNM vs controls. Cancer screening in IMNM should be individualized based on age-personal and family history, including consideration of FDG-PET/CT. Immune-treatment response did not differ with cancer.

Human transcriptomic response to periprosthetic joint infection.

Periprosthetic joint infection (PJI), a devastating complication of total joint replacement, is of incompletely understood pathogenesis and may sometimes be challenging to clinically distinguish from other causes of arthroplasty failure. We characterized human gene expression in 93 specimens derived from surfaces of resected arthroplasties, comparing transcriptomes of subjects with infection- versus non-infection-associated arthroplasty failure. Differential gene expression analysis confirmed 28 previously reported potential biomarkers of PJI, including bactericidal/permeability increasing protein (BPI), cathelicidin antimicrobial peptide (CAMP), C-C-motif chemokine ligand 3 (CCL3), 4(CCL4) and C-X-C-motif chemokine ligand 2 (CXCL2), colony stimulating factor 2 receptor beta (CSF2RB), colony stimulating factor 3 (CSF3), alpha-defensin (DEFA4), Fc fragment of IgG receptor 1B (CD64B), intercellular adhesion molecule 1 (ICAM1), interferon gamma (IFNG), interleukin 13 receptor subunit alpha 2 (IL13RA2), interleukin 17D (IL17D), interleukin 1 (IL1A, IL1B, IL1RN), interleukin 2 receptors (IL2RA, IL2RG), interleukin 5 receptor (IL5RA), interleukin 6 (IL6), interleukin 8 (IL8), lipopolysaccharide binding protein (LBP), lipocalin (LCN2), lactate dehydrogenase C (LDHC), lactotransferrin (LTF), matrix metallopeptidase 3 (MMP3), peptidase inhibitor 3 (PI3), and vascular endothelial growth factor A (VEGFA), and identified three novel molecules of potential diagnostic use for detection of PJI, namely C-C-motif chemokine ligand CCL20, coagulation factor VII (F7), and B cell receptor FCRL4. Comparative analysis of infections caused by staphylococci versus bacteria other than staphylococci and Staphylococcus aureus versus Staphylococcus epidermidis showed elevated expression of interleukin 13 (IL13), IL17D, and MMP3 in staphylococcal infections, and of IL1B, IL8, and platelet factor PF4V1 in S. aureus compared to S. epidermidis infections. Pathway analysis of over-represented genes suggested activation of host immune response and cellular maintenance and repair functions in response to invasion of infectious agents. The data presented provides new potential targets for diagnosis of PJI and for differentiation of PJI caused by different infectious agents.

Outcomes of a Stress Management and Resiliency Training (SMART) Program for Family Caregivers of Individuals With Advanced Head and Neck Cancer.

OBJECTIVES: To conduct a single-arm prospective pilot study examining the feasibility, acceptability, and preliminary effectiveness of a Stress Management and Resiliency Training (SMART) intervention among family caregivers (FCGs) of individuals with head and neck cancer (HNC). SAMPLE & SETTING: This study was conducted with 26 FCGs of individuals with HNC receiving chemotherapy in the medical oncology clinic at the Mayo Clinic Comprehensive Cancer Center. METHODS & VARIABLES: The SMART intervention consisted of in-person and online components. Measurements included feasibility, acceptability, self-compassion, resilience, perceived stress, anxiety, and mindfulness. RESULTS: Results support acceptability of the SMART program and provide recommendations to improve feasibility. Data indicate significant improvements in self-compassion (p = 0.03) and anxiety (p = 0.02), with positive trends for resilience, stress, and mindfulness. IMPLICATIONS FOR NURSING: This study warrants further research with larger, more diverse samples testing the efficacy of the program, its mechanism of action, and potential synergistic effects among individuals receiving oncology care, FCGs, and nurses.

Inclusion body myositis: correlation of clinical outcomes with histopathology, electromyography and laboratory findings.

OBJECTIVE: To determine whether histopathological, electromyographic and laboratory markers correlate with clinical measures in inclusion body myositis (IBM). METHODS: We reviewed our electronic medical records to identify patients with IBM according to European Neuromuscular Center (ENMC) 2011 criteria, seen between 2015 and 2020. We only included patients who had a muscle biopsy and needle electromyography (EMG) performed on the same muscle (opposite or same side). We used a detailed grading system [0 (normal) to 4 (severe)] to score histopathological and EMG findings. Clinical severity was assessed by the modified Rankin scale (mRS), muscle strength sum score (SSS), quadriceps strength and severity of dysphagia on swallow evaluation. Serum markers of interest were creatine kinase level and cN-1A antibodies. RESULTS: We included 50 IBM patients, with a median age of 69 years; 64% were males. Median disease duration at diagnosis was 51 months. On muscle biopsy, endomysial inflammation mainly correlated with dysphagia, and inversely correlated with mRS. Vacuoles and congophilic inclusions did not correlate with any of the clinical measures. On EMG, the shortness of motor un it potential (MUP) duration correlated with all clinical measures. Myotonic discharges, and not fibrillation potentials, correlated with the severity of inflammation. Serum markers did not have a statistically significant correlation with any of the clinical measures. CONCLUSIONS: Dysphagia was the main clinical feature of IBM correlating with endomysial inflammation. Otherwise, inclusion body myositis clinical measures had limited correlation with histopathological features in this study. The shortness of MUP duration correlated with all clinical measures.

Survival and associated comorbidities in inclusion body myositis.

OBJECTIVE: To evaluate survival and associated comorbidities in inclusion body myositis (IBM) in a population-based, case-control study. METHODS: We utilized the expanded Rochester Epidemiology Project medical records-linkage system, including 27 counties in Minnesota and Wisconsin, to identify patients with IBM, other inflammatory myopathies (IIM), and age/sex-matched population-controls. We compared the frequency of various comorbidities and survival among groups. RESULTS: We identified 50 IBM patients, 65 IIM controls and 294 population controls. Dysphagia was most common in IBM (64%) patients. The frequency of neurodegenerative disorders (dementia/parkinsonism) and solid cancers was not different between groups. Rheumatoid arthritis was the most common rheumatic disease in all groups. A total of 36% of IBM patients had a peripheral neuropathy, 6% had Sjögren's syndrome and 10% had a haematologic malignancy. T-cell large granular lymphocytic leukaemia was only observed in the IBM group. None of the IBM patients had hepatitis B or C, or HIV. IBM patients were 2.7 times more likely to have peripheral neuropathy, 6.2 times more likely to have Sjögren's syndrome and 3.9 times more likely to have a haematologic malignancy than population controls. IBM was associated with increased mortality, with a 10-year survival of 36% from index, compared with 67% in IIM and 59% in population controls. Respiratory failure or pneumonia (44%) was the most common cause of death. CONCLUSIONS: IBM is associated with lower survival, and higher frequency of peripheral neuropathy, Sjögren's syndrome and haematologic malignancies than the general population. Close monitoring of IBM-related complications is warranted.

Objective sleep profile in LGI1/CASPR2 autoimmunity.

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) and other sleep disturbances are frequent in leucine-rich, glioma inactivated protein 1-IgG (LGI1) and contactin-associated protein 2-IgG (CASPR2) autoimmunity, yet polysomnographic analyses of these disorders remain limited. We aimed to characterize clinical presentations and analyze polysomnographic manifestations, especially quantitative REM sleep without atonia (RSWA) in LGI1/CASPR2-IgG seropositive (LGI/CASPR2+) patients. METHODS: We retrospectively analyzed clinical and polysomnographic features and quantitative RSWA between LGI1+/CASPR2+ patients and age-sex matched controls. Groups were compared with Wilcoxon rank-sum and chi-square tests. Combined submentalis and anterior tibialis (SM + AT) RSWA was the primary outcome. RESULTS: Among 11 (LGI1+, n = 9; CASPR2+, n = 2) patients, Morvan syndrome sleep features were present in seven (63.6%) LGI1+/CASPR2+ patients, with simultaneous insomnia and dream enactment behavior (DEB) in three (27.3%), and the most common presenting sleep disturbances were DEB (n = 5), insomnia (n = 5), and sleep apnea (n = 8; median apnea-hypopnea index = 15/hour). Median Epworth Sleepiness Scale was nine (range 3-24; n = 10), with hypersomnia in four (36.4%). LGI1+/CASPR2+ patients had increased N1 sleep (p = .02), decreased REM sleep (p = .001), and higher levels of SM + AT any RSWA (p < .001). Eight of nine (89%) LGI1+ exceeded RBD RSWA thresholds (DEB, n = 5; isolated RSWA, n = 3). RSWA was greater in AT than SM. All 10 LGI1+/CASPR2+ patients treated with immunotherapy benefitted, and 5/10 had improved sleep disturbances. CONCLUSIONS: LGI1/CASPR2-IgG autoimmunity is associated with prominent dream enactment, insomnia, RSWA, sleep apnea, and shallower sleep. Polysomnography provides objective disease markers in LGI1+/CASPR2+ autoimmunity and immunotherapy may benefit associated sleep disturbances.

Association of Common Medications and the Risk of Early-Onset Gastric Cancer: A Population-Based Matched Study.

BACKGROUND: Early-onset gastric cancer (EOGC, age ≤ 60 years at diagnosis) now comprises >30% of new gastric cancers in the United States. It is hypothesized that chronic acid suppression with proton-pump inhibitors (PPIs) may promote tumorigenesis, while other medications including statins, nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, and cyclooxygenase-2 (COX-2) inhibitors have been proposed as protective. We aimed to assess for an association between use of the aforementioned commonly prescribed medications and EOGC development. METHODS: We used a population-based medical record linkage system, to identify cases of EOGC in Olmsted County, Minnesota, between January 1, 1995, and December 31, 2020. Patients were matched 1 : 1 with controls based on age at diagnosis, sex, smoking status, and body mass index (BMI). Conditional logistic regression was used to examine associations with the odds of EOGC development. RESULTS: Ninety-six cases of EOGC were identified during the study period. On both univariate and multivariate regression analysis, there was no significant association between use of PPIs, statins, NSAIDs, or metformin and EOGC development. In a final multivariable model, there was a significant reduction in odds of EOGC with COX-2 inhibitor use for six months or more prior to cancer diagnosis (OR = 0.39, 95% CI 0.16-0.94). CONCLUSION: In this retrospective, population-based study of individuals in Olmsted County, MN, we found significantly reduced odds of EOGC development associated with COX-2 inhibitor use for six months or more prior to diagnosis, but no association between EOGC development and use of PPIs and other commonly prescribed medications.

Utility of MRI Enhancement Pattern in Myelopathies With Longitudinally Extensive T2 Lesions.

OBJECTIVE: To determine whether MRI gadolinium enhancement patterns in myelopathies with longitudinally extensive T2 lesions can be reliably distinguished and assist in diagnosis. METHODS: We retrospectively identified 74 Mayo Clinic patients (January 1, 1996-December 31, 2019) fulfilling the following criteria: (1) clinical myelopathy; (2) MRI spine available; (3) longitudinally extensive T2 hyperintensity (≥3 vertebral segments); and (4) characteristic gadolinium enhancement pattern associated with a specific myelopathy etiology. Thirty-nine cases with alternative myelopathy etiologies, without previously described enhancement patterns, were included as controls. Two independent readers, educated on enhancement patterns, reviewed T2-weighted and postgadolinium T1-weighted images and selected the diagnosis based on this knowledge. These were compared with the true diagnoses, and agreement was measured with Kappa coefficient. RESULTS: Among all cases and controls (n = 113), there was excellent agreement for diagnosis using postgadolinium images (kappa, 0.76) but poor agreement with T2-weighted characteristics alone (kappa, 0.25). A correct diagnosis was more likely when assessing postgadolinium image characteristics than with T2-weighted images alone (rater 1: 100/113 [88%] vs 61/113 [54%] correct, p < 0.0001; rater 2: 95/113 [84%] vs 68/113 [60%] correct, p < 0.0001). Of the 74 with characteristic enhancement patterns, 55 (74%) were assigned an alternative incorrect or nonspecific diagnosis when originally evaluated in clinical practice, 12 (16%) received immunotherapy for noninflammatory myelopathies, and 2 (3%) underwent unnecessary spinal cord biopsy. CONCLUSIONS: Misdiagnosis of myelopathies is common. The gadolinium enhancement patterns characteristic of specific diagnoses can be identified with excellent agreement between raters educated on this topic. This study highlights the potential diagnostic utility of enhancement patterns in myelopathies with longitudinally extensive T2 lesions.

Clinical Utility of Striational Antibodies in Paraneoplastic and Myasthenia Gravis Paraneoplastic Panels.

OBJECTIVE: To critically assess the clinical utility of striational antibodies (StrAbs) within paraneoplastic and myasthenia gravis serological evaluations. METHODS: All Mayo Clinic patients tested for StrAbs from January 1st 2012-December 31st 2018 utilizing Mayo's Unified Data Platform (UDP) were reviewed for neurological diagnosis and cancer. RESULTS: 38,502 unique paraneoplastic and 1,899 MG patients were tested. In paraneoplastic evaluations, the StrAbs positivity rate was higher in cancer vs without cancer (5% [321/6775] vs 4% [1154/31727]; p<0.0001; OR 1.35; CI=1.19-1.53) but ROC analysis indicated no diagnostic accuracy in cancer (AUC=0.505). No neurological phenotype was significantly associated with StrAbs in the paraneoplastic group. Positivity was more common in all MG cancers compared to paraneoplastic cancers (p<0.0001). In MG evaluations, the StrAbs positivity rate was higher in those with cancer vs without (46% [217/474] vs 26% [372/1425]; p<0.0001; OR 2.39, CI 1.9-2.96) with ROC analysis indicating poor diagnostic accuracy for thymic cancer (AUC 0.634, recommended cutoff=1:60, sensitivity=56%, specificity=71%), with worse accuracy for extrathymic cancers (AUC 0.543). In paraneoplastic or MG evaluations, the value of antibody positivity did not improve cancer predictions. Paraneoplastic evaluated patients were more likely with positive StrAbs to obtain computed tomography (CT) (p=0.0001) with 3% (12/468) cancer found. CONCLUSION: Despite a statistically significant association with cancer, an expansive review of performance in clinical service demonstrates that StrAbs are neither specific nor sensitive in predicting malignancy or neurological phenotypes. CT imaging is over utilized with positive StrAbs results. Removal of StrAbs from paraneoplastic or MG evaluations will improve the diagnostic characteristics of the current MG test. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the presence of StrAbs do not accurately identify patients with malignancy or neurological phenotypes.

Epidemiology and Natural History of Inclusion Body Myositis: A 40-Year Population-Based Study.

OBJECTIVES: To determine the prevalence and natural history of sporadic inclusion body myositis (sIBM) and to test the hypothesis that patients with sIBM have higher cancer or mortality rates than the general population. METHODS: We sought patients with sIBM defined by the 2011 European Neuromuscular Centre (ENMC) diagnostic criteria among Olmsted County, Minnesota, residents in 40-year time period. RESULTS: We identified 20 patients (10 clinicopathologically defined, 9 clinically defined, and 1 probable) according to the ENMC criteria and 1 patient with all features of clinicopathologically defined sIBM except for symptom onset at <45 years of age. The prevalence of sIBM in 2010 was 18.20 per 100,000 people ≥50 years old. Ten patients developed cancers. The incidence of cancers in sIBM did not differ from that observed in the general population (odds ratio 1.89, 95% confidence interval [CI] 0.639-5.613, p = 0.24). Two-thirds of patients developed dysphagia, and half required a feeding tube. Nine patients required a wheelchair. The median time from symptom onset to wheelchair dependence was 10.5 (range 1-29) years. Overall life expectancy was shorter in the sIBM group compared to the general population (84.1 [95% CI 78-88.4] vs 87.5 [95% CI 85.2-89.5] years, p = 0.03). Thirteen patients died; 9 deaths were sIBM related (7 respiratory and 2 unspecified sIBM complications). Female sex (p = 0.03) and dysphagia (p = 0.05) were independent predictors of death. CONCLUSION: Olmsted County has the highest prevalence of sIBM reported to date. Patients with sIBM have similar risk of cancer, but slightly shorter life expectancy compared to matched patients without sIBM. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patients with sIBM have similar risks of cancers and slightly shorter life expectancy compared to controls.

Surgical Resection for Crohn's and Cancer: A Comparison of Disease-Specific Risk Factors and Outcomes.

BACKGROUND AND OBJECTIVES: The goal of this study was to compare disease-specific risk factors and 30-day outcomes between patients with Crohn's disease (CD) and colon cancer (CC) undergoing right-sided surgical resection. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP®) was interrogated to extract all patients ≥18 years undergoing elective right-sided resection for CD versus CC. Independent risk factors for surgical complications were identified through multivariable logistic regression for both groups. In a second step, surgical and medical 30-day morbidity was compared after risk adjustment. RESULTS: The cohort consisted of 17,516 patients, of which 2,899 (16.6%) underwent surgery for CD versus 14,617 (83.4%) for CC. Independent risk factors for surgical complications in patients with CD were male gender, African American race, ASA score (III or IV), active smoking, prolonged surgery, and preoperative anemia. Independent risk factors for surgical complications in the cancer group were age ≥70 years, male gender, ASA score (III or IV), respiratory and cardiovascular comorbidities, and preoperative hypoalbuminemia (<3.5 g/dL). After risk adjustment, surgical complications (OR 1.25, p = 0.002), sepsis (OR 1.64, p = 0.012), and unplanned readmissions (OR 1.39, p = 0.004) were more common in patients with CD. Thirty-day mortality was higher in cancer patients (1.1 vs. 0.1%, p < 0.0001). CONCLUSIONS: Patients with Crohn's disease were more prone to surgical complications and postoperative sepsis compared to the cancer group undergoing the same procedure. Careful evaluation and correction of disease-specific modifiable risk factors of patients with CD and CC, respectively, are important.

Bias Against Complex Lung Cancer Surgery.

BACKGROUND: Lung cancer remains a major public health problem. There remain differences in mortality among socioeconomic and racial groups. Using The Society of Thoracic Surgeons General Thoracic Surgery database, we attempted to determine whether there were differences in treatment choices by thoracic surgeons based on patients' race or insurance. METHODS: Using data from 2012 to 2017, we analyzed data from 75,774 patients with a diagnosis of lung cancer for whom complete information on race, insurance, or both was available, and who had undergone a pulmonary resection. We categorized 66,614 operations (87.9%) into standard (lobectomy, bilobectomy, or wedge excision) and 9160 (12.1%) into complex (pneumonectomy, sleeve or bronchoplastic resection, segmentectomy, or Pancoast resection) operations. Univariate and multiple variable logistic regression models were used to assess associations with receipt of a complex operation. RESULTS: Patients with private insurance had a higher incidence of complex operations (14.4%) compared with patients with government insurance (11.6%) (P < .0001). We also found a higher incidence of complex operations in White patients (12.2%) compared with Nonwhite patients (11.3%; P = .0054). On multivariate analysis, patients with private insurance were significantly more likely to have a complex operation (odds ratio = 1.08; P < .03) and Nonwhite patients were less likely to have a complex operation (odds ratio = 0.93; P = .04) respectively. CONCLUSIONS: In this cohort of patients from The Society of Thoracic Surgeons General Thoracic Surgery database, White patients and those with private insurance had a higher incidence of complex operations. Many factors affect the decision to proceed with a complex thoracic surgical operation; type of medical insurance and race may represent 2 of them.

Anti-cN1A antibodies do not correlate with specific clinical, electromyographic, or pathological findings in sporadic inclusion body myositis.

BACKGROUND: Anti-cytosolic 5'-nucleotidase 1A (cN1A) antibodies are commonly detected in patients with sporadic inclusion body myositis (sIBM). However, their pathogenic role has not been established. Moreover, efforts toward identifying sIBM distinct clinicopathologic characteristics associated with these antibodies have yielded conflicting results. METHODS: We first searched for patients, seen in our clinics, tested for anti-cN1A antibodies between December 2015 and December 2019. We identified 92 patients who were diagnosed with sIBM, according to the 2011 ENMC or Griggs et al criteria. Thereafter, we reviewed and compared the clinical and investigational findings of these patients in relation to their antibody status. RESULTS: Anti-cN1A antibodies were present in 47/92 (51%) patients with sIBM. Comparison of seropositive and seronegative cohorts yielded no significant difference in clinical features, including facial weakness, oropharyngeal and respiratory involvement, or disease severity. The antibody titer did not correlate with the clinical phenotype, CK value, or presence of myotonic discharges on EMG. Anti-cN1A antibody positive patients appeared to have more frequent auto-aggressive inflammation on muscle biopsy but not as an isolated myopathological feature. CONCLUSIONS: Our study showed that anti-cN1A antibody positive and negative sIBM patients have similar clinical features and disease severity. Anti-cN1A antibodies in our sIBM cohort did not correlate with any studied clinical or laboratory parameter and, therefore, were of limited value in the patient's assessment.

Burden and causes of readmissions following initial discharge after aortic syndromes.

BACKGROUND: Aortic syndromes, including aortic dissection (AD), intramural hematoma (IMH), and penetrating aortic ulcer (PAU), carry significant morbidity and mortality; few data exist regarding burden and causes of related rehospitalizations following initial discharge. METHODS: The study was conducted using the Rochester Epidemiology Project. All adult residents (age ≥18 years) with an incident diagnosis of AD, IMH, and PAU (1995-2015) were identified from the Rochester Epidemiology Project using the International Classification of Diseases, Ninth Revision and Tenth Revision codes and Hospital Adaptation of the International Classification of Diseases, second edition, codes. Assessment of any-cause (aortic and cardiovascular), aorta-related, or cardiovascular-related readmissions was determined following date of hospital discharge or diagnosis date (ie, the index event). RESULTS: A total of 117 patients of 130 cases of AD, IMH, and PAU included in the initial study population survived the index event and were evaluated. The median age of diagnosis was 74 years, and 70 (60%) were male. A total of 79 patients (68%) experienced at least one readmission. The median time to first any-cause, cardiovascular, and aortic readmission was 143, 861, and 171 days, respectively. The cumulative incidence of any-cause readmissions at 2, 4, and 10 years was 45%, 55%, and 69%, respectively. The cumulative incidence of cardiovascular readmissions at 2, 4, and 10 years was 15%, 20%, and 28%, respectively. The cumulative incidence of aortic readmissions at 2, 4, and 10 years was 38%, 46%, and 59%, respectively. Overall survival for the entire cohort at 2, 4, and 10 years was 84%, 75%, and 50%, respectively. CONCLUSIONS: Readmissions following initial discharge after diagnosis of aortic syndrome are common and not different across specific disease types. Whereas aorta-related rehospitalizations occur in more than half of patients but tend to be earlier, cardiovascular-related rehospitalizations tend to happen later in about one-third of patients. This may suggest the need for early follow-up focused on aortic complications, whereas later follow-up should address cardiovascular events.