Mayo Clinic Rochester Research Articles

Individualized prediction of critical illness in older adults: Validation of an elders risk assessment model.

The electronic health record (EHR) presents new opportunities for the timely identification of patients at high risk of critical illness and the implementation of preventive strategies. This study aims to externally validate an EHR-based Elders Risk Assessment (ERA) score to identify older patients at high risk of future critical illness during a primary care visit. This historical cohort study included patients aged ≥65 years who had primary care visits at Mayo Clinic Rochester, MN, between July 2019 and December 2021. The ERA score at the time of the primary care visit was used to predict critical illness, defined as death or ICU admission within 1 year of the visit. A total of 12,885 patients were included in the analysis. The median age at the time of the primary care visit was 75 years, with 44.6% being male. 93.7% of participants were White, and 64.2% were married. The median (25th, 75th percentile) ERA score was 4 (0, 9). 11.3% of study participants were admitted to the ICU or died within 1 year of the visit. The ERA score predicted critical illness within 1 year of a primary care visit with an area under the receiver operating characteristic curve of 0.84 (95% CI 0.83-0.85), which indicates good discrimination. An ERA score of 9 was identified as optimal for implementing and testing potential preventive strategies, with the odds ratio of having the primary outcome in patients with ERA score ≥9 being 11.33 (95%CI 9.98-12.87). This simple EHR-based risk assessment model can predict critical illness within 1 year of primary care visits in older patients. The findings of this study can serve as a basis for testing and implementation of preventive strategies to promote the well-being of older adults at risk of critical illness and its consequences.

Telemedicine in Oculoplastic Surgery During the COVID-19 Pandemic: A Single Center Experience.

Purpose: To investigate patterns in oculoplastic surgery telemedicine visits at our institution during the pandemic period. Methods: Retrospective chart review of all patients who had a virtual consultation with the oculoplastic surgery service at Mayo Clinic Rochester between March 1, 2020, and March 1, 2021. Results: There were a total of 148 patients. Mean age was 65 years (95% confidence interval [CI]: 62-68). The mean driving distance to the medical center was 468 kilometers (95% CI: 352-586) and 15 (10%) patients came from states with no practicing American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) members. Out of the 205 virtual visits, 35 (17%) were new, 45 (22%) were return, and 125 (61%) were postoperative. Conversion rate to surgery was 60%. A comparison between type of virtual visits (new vs. return vs. postoperative) revealed that a diagnosis of eyelid malposition was most frequent in postoperative visits (p = < 0.001), skin malignancy was most frequent in new visits (p = 0.009), and orbital tumors (p = 0.018) and thyroid eye disease (p = < 0.001) were most frequent in return visits. Most virtual encounters had supportive media attached including external photographs in 127 (62%) visits and other imaging or testing in 18 (9%) visits. The average virtual visit lasted 18 min (95% CI: 14-22) with technical difficulties noted in 9 (4%) visits. Unanticipated conversion to in-person visits was noted in three (1%) cases. Conclusions: A wide range of oculoplastic surgery conditions was managed virtually during the COVID-19 pandemic. Utilization of initial virtual visit versus follow-up care varied by diagnosis. Virtual visits may improve access to oculoplastic subspecialty care for patients from underserved areas.

Clinical outcomes of atezolizumab versus standard-of-care docetaxel with and without ramucirumab in patients with advanced non-small-cell lung cancer who received prior immunotherapy.

Atezolizumab is superior to docetaxel for patients with advanced non-small-cell lung cancer (NSCLC) who are pretreated with platinum-based chemotherapy based on the POPLAR and OAK trials. However, patients who received prior immunotherapy were excluded from these trials. The standard of care second-line therapy for these patients remains to be docetaxel with or without ramucirumab. The efficacy and safety of atezolizumab as a subsequent therapy in immunotherapy-pretreated patients are unknown. We conducted a retrospective study of all patients with locally advanced or metastatic NSCLC who were pretreated with immunotherapy at Mayo Clinic Jacksonville and Rochester from 2016 to 2022. Patients who received subsequent therapy of atezolizumab alone (Atezo), docetaxel (Doce), or docetaxel + ramucirumab (Doce+Ram) were included. In this cohort of 165 patients, 12.7% (n=21), 49.1% (n=81), and 38.2% (n=63) patients received subsequent Atezo, Doce, and Doce+Ram, respectively. 1-year landmark progression-free survival (PFS) were 23.8%, 6.2%, and 3.2% (p=0.006), and 2-year landmark PFS were 14.3%, 0%, and 0% (p<0.0001), in the Atezo, Doce, and Doce+Ram groups, respectively. About 20% patients with positive PD-L1 had durable response to atezolizumab. The Atezo group showed significantly greater overall survival (OS) improvement over Doce group (median OS 17.7 vs. 7.7 months, HR 0.47, 95% CI 0.29 - 0.76, p=0.008), and over Doce+Ram group (median OS 17.7 vs. 8.9 months, HR 0.55, 95% CI 0.32 - 0.95, p=0.047). 4 of 21 (19%) patients in the Atezo group developed immune-related adverse events (irAE). We observed statistically significant and clinically meaningful overall survival benefits of atezolizumab monotherapy compared with docetaxel +/- ramucirumab in patients with advanced NSCLC who were pretreated with immunotherapy. The survival benefit seems to be mainly from PD-L1 positive patients. Subsequent immunotherapy with Atezolizumab did not increase irAE rate.

Diagnostic Performance of a Fecal Calprotectin Assay as a Biomarker for Mayo Endoscopic Subscore in Ulcerative Colitis: Result From a Tertiary Referral Center.

Fecal calprotectin (FC) is a promising biomarker for assessing ulcerative colitis (UC) endoscopic activity. However, the optimal FC cutoff to identify each Mayo endoscopic subscore (MES) remains inconclusive. The electronic medical records of 177 adult UC patients evaluated at Mayo Clinic Rochester from January 2017 to March 2023 were retrospectively reviewed, obtaining clinical data and US-based Werfen Diagnostics FC levels collected within 30 days before colonoscopy or flexible sigmoidoscopy. Three independent inflammatory bowel disease specialist endoscopists blindly reviewed the most severe endoscopic images for grading MES. The median interval between FC collection and endoscopy was 2 days. Fecal calprotectin showed strong positive correlations with MES (Spearman's r = 0.709; P < .01) and other clinical parameters. Fecal calprotectin cutoff of 60 mcg/g effectively distinguished MES 0 from MES 1-3 (sensitivity, 0.78; specificity, 0.97; area under the receiver operating characteristic curve [AUC], 0.901) and predicted clinical remission (Total Mayo Score ≤2 and no subscore >1; sensitivity, 0.83; specificity, 0.98; AUC, 0.921). Fecal calprotectin cutoff of 110 mcg/g effectively differentiated MES 0-1 from MES 2-3 (sensitivity, 0.86; specificity, 0.87; AUC, 0.915), while a cutoff of 310 mcg/g distinguished MES 0-2 from MES 3 (sensitivity, 0.80; specificity, 0.76; AUC, 0.820). This study supports the reliability and applicability of FC as a valuable marker of endoscopic inflammation, particularly in distinguishing MES 0 from MES 1-3 using the FC cutoff of 60 mcg/g. Sensitivity analysis demonstrated robust results.

Outcomes for patients with mCRPC and liver metastasis receiving 177-Lu-PSMA-617 treatment.

175 Background: It is well-known that patients with liver metastases from metastatic castration resistant prostate cancer (mCRPC) have poorer or transient responses to many forms of systemic therapy. Data on outcomes following treatment with Lutetium-177–PSMA-617 is scarce. The VISION trial reports hazard ratios for overall survival in the subgroup of patients with liver metastases without disclosing the absolute duration of survival. Using real-world clinical data, we examine this important subgroup of patients, describing their PSA response rates and survival. Methods: A single institution database was assembled to include all patients receiving 177-Lu-PSMA-617 at Mayo Clinic Rochester, MN, and starting treatment in the interval of March 2022 to March 2023. Baseline clinicopathologic and imaging characteristics were abstracted. Patients were categorized based on the presence or absence of measurable liver metastases on their baseline PSMA PET scan. Best PSA response while on treatment was annotated and reported as percent decline from baseline. Survival was calculated from date of first cycle of 177-Lu-PSMA-617. PSA50 response and overall survival (OS) outcomes for the two groups (liver metastases versus no liver metastases) were compared using Chi square test and Kaplan-Meier method, respectively. Those with available pre-treatment circulating tumor DNA (ctDNA) genomic profiling, performed by Guardant (83 gene panel), were assessed for the presence of pathogenic and likely pathogenic alterations. Findings are summarized using descriptive statistics. Results: The overall cohort consisted of 212 patients, including 29 (14%) with liver metastases on pre-treatment PSMA PET/CT. The median number of cycles received was 4 (range, 1-6) for patients with liver metastases and 6 (range, 1-6) for those without hepatic involvement. The observed PSA50 response trended lower for those with liver metastases (34.5% [10/29] versus 51% [94/183], p= 0.091). At median (IQR) follow-up of 10 (8-12) months, there was a numerical but not statistically significant difference in median OS (11.28 months versus NR, p=0.066). In the exploratory analysis of baseline ctDNA, BRCA2 copy number loss was relatively enriched among patients with liver metastases (4 of 19, 21%) versus patients without liver disease (5.7%, 9/158). Conclusions: Our data suggest that the presence of liver metastases predict poorer outcomes in patients receiving Lutetium-177–PSMA-617 treatment, which is similar to data reported with other forms of systemic therapy for mCRPC. To maximize the anti-tumor activity of radioligand therapy in the liver, combination approaches should be explored.

Characteristics, clinical outcomes, and prognostic factors of colorectal cancer in patients with Crohn's disease: American versus Korean tertiary referral center perspectives.

Crohn's disease (CD) exhibits variability in colorectal cancer (CRC) incidence and prognostic factors due to diverse clinical and behavioral characteristics, presenting inconsistencies between Western and Eastern patients. This study compared clinical characteristics between CD patients with CRC from the US and Korean tertiary referral centers and defined the prognostic factors related to mortality. Retrospective study. We reviewed the electronic medical records of 236 adult CD patients with colorectal adenocarcinoma evaluated at Mayo Clinic Rochester, Florida, or Arizona (N = 200) and Asan Medical Center in Korea (N = 36) between January 1989 and August 2022. Asan patients had a younger age, shorter CD duration, more colonic involvement (L2 plus L3), penetrating behavior, perianal fistula, and shorter biological treatment duration before CRC diagnosis than Mayo patients. Furthermore, despite significant differences in body mass index, smoking status, primary sclerosing cholangitis, immunomodulators, CRC diagnosis period, clinical presentation, CRC location, surgery, and some histopathological details between the two groups, overall survival was not statistically different (p value, 0.29, log-rank test). Advanced age (adjusted hazard ratio (aHR), 1.03 per year; 95% confidence interval (CI), 1.01-1.04; p value, <0.01), unresectable CRC (aHR, 5.02; 95% CI, 2.49-10.12; p value, <0.01), and advanced CRC stage (aHR, 1.45 per stage; 95% CI, 1.07-1.97; p value, 0.02) were significantly associated with increased risk of death. CD remission at CRC diagnosis (aHR, 0.26; 95% CI, 0.08-0.91; p value, 0.04), CRC diagnosis period of 2011-2022 (aHR relative to 1989-2000, 0.46; 95% CI, 0.25-0.87; p value, 0.02), and CRC diagnosis by surveillance (aHR, 0.56; 95% CI, 0.32-0.98; p value, 0.04) were significantly associated with decreased risk of death. Notably, some clinical features of CD with CRC differed between Asan and Mayo patients; however, overall survival was not different. CD remission, CRC surveillance, and more recent diagnosis of CRC were associated with a reduced risk of death.

PRELIMINARY FEASIBILITY, UTILITY, AND ACCEPTABILITY OF THE TBI-AD/ADRD CAREGIVER SUPPORT INTERVENTION (TACSI)

Abstract Research has established that dementia care partners may encounter socio-emotional and physical health concerns as a consequence of providing dementia care. Similarly, care partners for people living with Traumatic Brain Injury (TBI) often experience a range of stressors and negative mental health outcomes due to their care demands. This study aims to support the unique subset of family care partners facing the challenge of caring for relatives who have both diseases, Alzheimer’s Disease/Alzheimer’s Disease related dementia (AD/ADRD) and a history of TBI. Phase I of this study focused on the design and subsequent refinement of the TBI-AD/ADRD Caregiver Support Intervention (TACSI). TACSI is a six-session telehealth intervention providing tailored psychosocial and psychoeducational coaching. Session topics include education on TBI and dementia, stress management, lifestyle planning, and communication skills. In partnership with the Minneapolis VA and the Mayo Clinic-Rochester, we enrolled 15 care partners for Phase I. Mixed methods data from 3-month follow-up surveys and qualitative data from post-intervention interviews established the feasibility, utility, and acceptance of TACSI. Care partners found the program valuable and would recommend it to others. They reported that TACSI helped with their stress management. Some participants shared that TACSI would provide greater benefit to newer caregivers needing more education on the diseases and/or caregiving. Phase I feedback will be applied to improve TACSI content and delivery for the Phase II randomized controlled trial evaluation. TACSI Phase I utility, acceptance, and feasibility outcomes will be highlighted as well as next steps for evaluation.

P127 Characteristics and outcomes of geriatric patients with depression who received pharmacogenomic testing for antidepressant medication selection

Objective:Pharmacogenomic testing for antidepressant medication selection is widely available, and patients with treatment-resistant depression regularly inquire about it. Psychiatrists and primary care providers have little guidance on when to obtain pharmacogenomic testing. We reviewed the characteristics and outcomes of a sample of geriatric patients who received this testing.Methods:Retrospective review of patients ages 65 and older with ICD-10 diagnoses of depressive disorders (F32.0-F33.9), followed at Mayo Clinic Rochester, who received pharmacogenomic testing between 1/1/2018 and 12/31/2022 to guide antidepressant medication selection. Patients were included if there were Patient Health Questionnaire 9-item (PHQ-9) depression rating scores up to 3 months before and 3 months after pharmacogenomic testing. Demographic information, cytochrome P-450 CYP2D6 and CYP2C19 phenotypes, PHQ-9 scores, ordering provider (psychiatrist or primary care provider), and resulting medication changes were collected. Paired t-tests compared differences between before and after PHQ-9, with statistical significance p&lt;0.05.Results:Approximately 1% of patients with a depressive disorder received pharmacogenomic testing. After limiting to patients with PHQ-9 before and after testing, 287 patients met inclusion criteria. 66% were female, mean age 72.3 yrs (±SD 5.7, range 65.0-90.7), and 95% were Caucasian. CYP2D6 phenotypes were 9% poor, 48% intermediate, 39% extensive (normal), 3% rapid metabolizer. CYP2C19 phenotypes were 3% poor, 25% intermediate, 39% extensive, 33% rapid metabolizer. Mean PHQ-9 before testing was 10.8 (±SD 6.4), and after testing was 9.8 (±SD 6.5) (p=0.0041). Data collection regarding ordering provider and medication changes were still pending.Conclusion:The clinical utilization of pharmacogenomic testing appeared to be low. CYP2D6 and CYP2C19 phenotypes were as expected (except for more 2C19 rapid metabolizers), suggesting treatment resistance was less likely related to these genetic factors. There was a statistically significant decrease of 1 point in the mean PHQ-9, which would not be clinically significant. However, many other factors still need to be explored, such as details about medications and gene-medication interactions, ordering provider’s knowledge about pharmacogenomic testing, whether medication changes were made, aging factors influencing pharmacokinetics, medical and psychosocial burdens, and other concurrent treatments. Further research will hopefully allow more practical guidance on whether and when to obtain pharmacogenomic testing.

Physical Inactivity and Social Determinants of Health Among Older Adults with Mild Cognitive Impairment and Dementia

AbstractBackgroundPhysical activity can improve the physical health of people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is important. We examined the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia.MethodWe included people with a diagnosis of MCI or dementia, age 55 years and older, who were empaneled to Community Internal Medicine at Mayo Clinic (Rochester, Minnesota), had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity and transportation needs. Self‐reported activity levels were categorized as inactive (0 minutes of exercise per week), insufficiently active (10‐140 minutes per week) or sufficiently active (≥150 minutes per week). SDOH domains were compared according to physical activity level using χ2 tests and multinomial logistic regression.ResultA total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, depression risk and increased social isolation (all p&lt;0.001).ConclusionPhysical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many modifiable factors, highlighting potential areas for intervention in this population.

Exploring social determinants of health and physical activity levels in older adults living with mild cognitive impairment and dementia in the Upper Midwest of the United States

BackgroundPhysical activity can improve physical health for people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is needed. We sought to examine the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia. MethodsThis descriptive study included people with a diagnosis of MCI or dementia followed by Community Internal Medicine at Mayo Clinic (Rochester, Minnesota, United States), aged over 55 years, who had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity, and transportation needs. Data were analyzed based on physical activity level (inactive, insufficiently active, sufficiently active). SDOH domains were compared according to physical activity level using the χ2 test and multinomial logistic regression. ResultsA total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, screening positive for depression and increased social isolation (p < 0.001). ConclusionsPhysical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many factors, highlighting potential areas for intervention.

NCOG-37. BELZUTIFAN IN ADULTS WITH VHL-ASSOCIATED CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMA: A SINGLE-CENTER EXPERIENCE

Abstract INTRODUCTION Belzutifan is a selective inhibitor of hypoxia-inducible factor 2-alpha that has been FDA approved for Von Hippel–Lindau (VHL) syndrome-associated tumors. There is limited real-world evidence in CNS hemangioblastoma. Our objective was to report on our clinical experience with belzutifan. METHODS We retrospectively reviewed our institutional (Mayo Clinic Rochester) experience of belzutifan in adults (18 years or older) with VHL and craniospinal hemangioblastomas not amenable to surgery. The study period was October 2021 to March 2023. RESULTS 4 patients (all female) with a median age of 36 years at time of belzutifan initiation were included. Median duration of therapy at last follow-up was 11 months (6-17 months). All patients had radiographic response to therapy after a median of 3 months (2-5 months), with maximal response to therapy after a median of 8 months (3-17 months). Therapy was well tolerated. The most common adverse effect was anemia. No patients had treatment pauses or dose adjustments due to toxicity. No patients experienced hypoxia. DISCUSSION We showed that belzutifan is safe and well-tolerated with strong disease response for CNS hemangioblastoma in adults with VHL, supporting continued use of belzutifan in this patient population. Future studies should assess duration of treatment, effects of cessation after long-term use, and markers of therapeutic response.

Echocardiography-Based Deep Learning Model to Differentiate Constrictive Pericarditis and Restrictive Cardiomyopathy

BackgroundConstrictive pericarditis (CP) is an uncommon but reversible cause of diastolic heart failure if appropriately identified and treated. However, its diagnosis remains a challenge for clinicians. Artificial intelligence may enhance the identification of CP. ObjectivesThe authors proposed a deep learning approach based on transthoracic echocardiography to differentiate CP from restrictive cardiomyopathy. MethodsPatients with a confirmed diagnosis of CP and cardiac amyloidosis (CA) (as the representative disease of restrictive cardiomyopathy) at Mayo Clinic Rochester from January 2003 to December 2021 were identified to extract baseline demographics. The apical 4-chamber view from transthoracic echocardiography studies was used as input data. The patients were split into a 60:20:20 ratio for training, validation, and held-out test sets of the ResNet50 deep learning model. The model performance (differentiating CP and CA) was evaluated in the test set with the area under the curve. GradCAM was used for model interpretation. ResultsA total of 381 patients were identified, including 184 (48.3%) CP, and 197 (51.7%) CA cases. The mean age was 68.7 ± 11.4 years, and 72.8% were male. ResNet50 had a performance with an area under the curve of 0.97 to differentiate the 2-class classification task (CP vs CA). The GradCAM heatmap showed activation around the ventricular septal area. ConclusionsWith a standard apical 4-chamber view, our artificial intelligence model provides a platform to facilitate the detection of CP, allowing for improved workflow efficiency and prompt referral for more advanced evaluation and intervention of CP.

Femoral neuropathy: A clinical and electrodiagnostic review.

Femoral neuropathies can cause severe, prolonged debility, yet there have been few clinical and electrodiagnostic (EDx) studies addressing this condition. The aim of this study was to better understand the etiologies, EDx features, and clinical course of femoral neuropathy. We identified patients evaluated at Mayo Clinic Rochester between January 1, 1999 and July 31, 2019, with possible new femoral neuropathy ascertained via International Classification of Diseases-versions 9 and 10 diagnosis codes presenting within 6 months of symptom onset. A retrospective review of 1084 records was performed and we ultimately identified 159 patients with isolated femoral neuropathy for inclusion. The most common femoral neuropathy etiologies were compressive (40%), perioperative stretch (35%), and inflammatory (6%). Presenting symptoms included weakness (96%), sensory loss (73%), and pain (53%). Presenting motor physical exam findings demonstrated moderate weakness (34%) or no activation (25%) of knee extension and mild (32%) or moderate (35%) weakness of hip flexion. Seventy-two percent of patients underwent EDx testing, including 22 with femoral motor nerve conduction studies. Treatment often involved physical therapy (89%) and was otherwise etiology-specific. In patients with follow-up data available (n = 154), 83% had subjective clinical improvement at follow-up with a mean time to initial improvement of 3.3 months and mean time to recovery at final follow-up of 14.8 months. Only 48% of patients had nearly complete or complete recovery. In our cohort, the most common etiologies of femoral neuropathy were compression or perioperative stretch with high initial morbidity. Although motor recovery is common, improvement is often prolonged and incomplete.

Modified Staging System for Waldenström Macroglobulinemia (MSS-WM): A Multi-Institutional Externally Validated Prognostic Model for Active/Symptomatic Waldenström Macroglobulinemia

Background: Waldenström Macroglobulinemia (WM) is an indolent lymphoma with heterogeneous outcomes. The recently developed, Revised International Prognostic Scoring System for WM (rIPSS-WM) did not examine the prognostic impact of MYD88L265P, a somatic alteration present in most patients with WM. Moreover, rIPSS-WM could only be partially validated in an external cohort. Here, we report the performance of rIPSS-WM and propose a refined prognostic model with external validation. Methods: We reviewed medical records of treatment-naïve patients with active WM consecutively seen at Mayo Clinic, Rochester (MCR) between 01/01/1996 and 12/31/2017. We applied the rIPSS-WM model in patients with data available for all required parameters, including age, serum beta-2 microglobulin (β2M), serum lactate dehydrogenase (LDH) and serum albumin at diagnosis to assess the prognostic utility of this model. We then identified the dichotomized clinical and laboratory parameters prognostic for overall survival (OS) by univariate analyses (UVA) in our cohort. The significant parameters were analyzed to independently predict OS in a multivariable analysis (MVA) and to create a prognostic model, which was subsequently validated in an independent multi-institutional cohort. Results: We identified 889 patients with active WM at MCR, with a median follow-up of 8.2 [95% confidence interval (CI): 7.5-9] years. The estimated median OS for this cohort was 10.6 (95%CI: 9.7-11.4) years. Patients with available data in this cohort for the validation of rIPSS-WM (n=241) were risk stratified into very low (n=46), low (n=64), intermediate (n=58), high (n=46) and very-high risk groups (n=27) per rIPSS-WM, with the respective 5-year OS rates of 96%, 76%, 72%, 77% and 32%, demonstrating overlapping survival curves for the low, intermediate and the high-risk groups. Because rIPSS-WM could not be validated, we used the data from the MCR cohort and identified age at diagnosis of active WM, LDH &amp;gt;upper limit of normal (ULN), β2M &amp;gt;3µg/mL and albumin &amp;lt;3.5g/dL as statistically significant prognostic markers for OS on UVA. Notably, the presence of MYD88 L265P did not impact OS [median 11.4 years (95%CI: 10.1-not reached (NR) for MYD88 L265P genotype (n=231) versus 10 years (95% CI: 8.1-NR) for MYD88 WT genotype (n=65); p=0.33]. On MVA, LDH &amp;gt;ULN (HR 2.34), serum albumin &amp;lt;3.5 g/dL (HR 1.5) and age groups 65-75 years (HR 1.4) and &amp;gt;75 years (HR 2.6) were independently prognostic. Based on comparable HRs, we assigned a score of 1 point each to serum albumin &amp;lt;3.5 g/dL and age group 66-75 years and similarly, 2 points each for age &amp;gt;75 years and serum LDH &amp;gt;ULN per their impact on OS. Patients with the composite scores of 0, 1 and 2 were categorized as low risk, low- intermediate risk and intermediate risk, respectively. Due to similar OS for the scores of 3 to 5, these were combined to form the high-risk group of our proposed model: Modified Staging System for WM (MSS-WM). The median OS was 14.6 years [95%CI: 9.1 years-NR] for low-risk (score 0, n=71, 21%), 11.2 years (95% CI: 9.1-15.2 years) for low-intermediate risk (score 1, n=110, 32%), 8.1 years (95% CI: 6.4-12.2) for intermediate risk (score 2, n=81, 24%) and 5.5 years (95 % CI: 3.9-11 years) for the high-risk group (score ≥3, n=79, 23%); p&amp;lt;0.0001. In this derivation cohort, the 5-year OS rate was 93%, 82%, 69% and 55% and 10-year OS rate was 60%, 53%, 45% and 30% for the low, low-intermediate, intermediate, and high-risk cohort, respectively ( Figure 1A). We also validated MSS-WM using competing risk analysis (p=0.001) and in the cohort of rituximab treated patients (p&amp;lt;0.0001). We then used data from an independent series of 335 treatment-naïve symptomatic patients from academic institutions (n=5) across the US and Europe for external validation of the MSS-WM model. The median follow-up for the validation cohort was 6.3 years (95% CI: 5.5-7.2 years). The 5-year OS was 93%, 90%, 75% and 57% and the estimated 10-year OS was 91%, 80%, 64% and 35% for the low risk (n= 86, 26%), low-intermediate (n=107, 32%), intermediate (n=86, 26%) and high-risk (n=59, 18%) cohorts, respectively (p&amp;lt;0.0001, Figure 1B). Conclusions: Our proposed model, MSS-WM, is a simple, clinically useful, externally validated model that reliably risk stratifies previously untreated patients with active WM into four groups that have distinct outcomes based on the composite scores derived from the patients' age, serum albumin and serum LDH at diagnosis.

Healthcare Utilization Outcomes of Outpatient CAR-T Cell Therapy with Remote Patient Monitoring Program

Introduction While chimeric antigen receptor (CAR)-T cell therapy has transformed the management of hematologic malignancies, it requires frequent monitoring for acute toxicities, almost universally achieved through mandatory hospitalizations, therefore utilizing a significant amount of healthcare resources. At Mayo Clinic in Rochester, MN, our standard practice is administering CAR-T cell therapy in the outpatient setting through a multi-disciplinary hospital-based outpatient (HBO) unit and remote patient monitoring (RPM) program. Our CAR-T RPM program consists of in-home, electronic health record-integrated technology to monitor vital signs and neurologic symptoms for 30 days post CAR-T infusion. Here we report the healthcare utilization outcomes of CAR-T patients managed in the outpatient setting enrolled in the RPM program. Methods Patients undergoing FDA-approved CAR-T cell treatment in the outpatient setting and participating in the CAR-T RPM program at Mayo Clinic Rochester were included in this IRB-approved study. Patient characteristics, healthcare utilization metrics, inpatient interventions, and patient satisfaction data regarding the RPM program were reviewed. Length of stay (LOS) includes any hospitalizations for which the admission date falls within the RPM monitoring period (CAR-T cell infusion to day +30), even if the hospitalization continued past day +30. Results A total of 123 patients participated in the CAR-T RPM program and underwent treatment in the outpatient setting. Median age at CAR-T infusion was 63 years (range 22 - 83), and most patients were male (n=78, 63%). Non-Hodgkin lymphoma was the most common diagnosis (n=74, 60%), followed by multiple myeloma (n=47, 38%), ALL (n=1, 1%) and other (n=1, 1%). During the PRM monitoring period, 19 (16%) patients were managed entirely in the outpatient setting. The remaining 104 (84%) patients required at least one hospitalization, with most patients (n=70, 57%) hospitalized only once [26 (21%) patients were hospitalized twice, and 7 (6%) patients were hospitalized 3 times, and 1 (1%) patient hospitalized 4 times during the monitoring period]. When considering the first hospitalization post CAR-T infusion, the median LOS was 6 days (range 2 - 47). When considering all hospitalizations post CAR-T, the median LOS was 8 days (range 2 - 47). Only 7 (6%) patients required an ICU stay, with a mean ICU stay of 0.2 days (standard deviation 0.9). Cytokine release syndrome (CRS) was noted in 92 (75%) of patients at a median of 3 days (range 0 - 18) post CAR-T infusion. All patients with CRS received tocilizumab, at a median of 4 days post CAR-T infusion. Steroids for CRS were administered in 63 (68%) of these patients. Neurotoxicity was reported in 45 (37%) patients at a median of 7 days (range 1 - 19) post CAR-T infusion. During the RPM monitoring period, patients were seen in our HBO unit with a median of 18 outpatient visits (range 4 - 30). Patient survey data, obtained at the end of the RPM monitoring period, were available from 37 patients. The majority of patients felt that the RPM program helped them feel comfortable managing their health at home, were able to reach a team member, and receive an appropriate response promptly. The majority of patients felt comfortable using the RPM equipment and interacting with providers virtually. Overall, 83% of patients were satisfied with the RPM program and 6% were neither satisfied nor dissatisfied. When asked about the reason for disappointment, technical difficulties/issues with the devices were the themes mentioned by the few patients (11%) who were unsatisfied with the RPM program. Conclusion: Despite the complexities and frequent monitoring associated with CAR-T cell therapy, outpatient CAR-T cell treatment is a feasible model of care. As the standard practice at our institution, the CAR-T RPM program was part of the management of nearly all patients undergoing an FDA-approved CAR-T product in the outpatient setting. RPM in the acute setting post CAR-T infusion is a well-received practice initiative by the majority of patients, including a high level of comfort utilizing the RPM equipment and virtual interaction with the RPM providers.

STAG2 and PHF6: Comparison of 2 X-Linked Gene Mutations in Myeloid Neoplasms

INTRODUCTION: The Stromal Antigen 2 ( STAG2), on Xq25, is the most common cohesin complex gene mutated in myeloid neoplasms (MN) (5-10%). STAG2 mutations ( STAG2m) were incorporated in the ELN2022 as AML-MDS defining genetic mutations inferring poor prognosis and is a genetic marker in IPSS-M risk stratification. The PHD-finger protein 6 ( PHF6) gene, on Xq26.3, is a tumor suppressor gene, mutated in 3% of MN, and is more common in T-ALL. PHF6m is believed to be a late event in MN with little data on its prognostic implications in MN. Both STAG2m and PHF6m are more prevalent in males, but their implications on the clinical presentation of MN have not been compared prior. METHOD: Our study is a multicenter study at Mayo Clinic (Rochester, Florida, Arizona). After IRB approval, we retrospectively analyzed charts of 7935 patients who had NGS between 2016-2022. STAG2m was found in 96 patients, and PHF6m in 116 (including 3 with concurrent STAG2m and PHF6m). We excluded 4 PHF6m patients who had T-ALL. Data was captured at time of NGS. MDS risk stratification was by IPSS-M and AML by ELN2022. Overall survival (OS) was calculated from date of NGS to date of last follow-up. BlueSky Software was used for statistical analysis. RESULTS: Characteristics: We compared 96 STAG2m vs 112 PHF6m MN patients. Of STAG2m cases, 78% were male vs 76% in PHF6m MN. Median age was 72 vs 73 years, respectively. Diagnoses included AML (29% of STAG2m vs 34% of PHF6m MN), MDS (54% vs 28%), MDS/MPN (10% vs 21%) and MPN (3% vs 9%). MDS was more common among STAG2m MN (p&amp;lt;.001) while MDS/MPN was more common among PHF6m MN (=.05). MDS-IB was the most common subtype in both (69% vs 52% in STAG2m vs PHF6m MDS). MDS-LB and 5q subtypes were only found in PHF6m MDS, and there was more PHF6m MDS-RS (13% vs 2%). Median IPSS-M score was 0.9 vs 0.8 in STAG2m vs PHF6m MDS (both high-risk). Majority of STAG2m AML were adverse risk (96%) while PHF6m AML were intermediate (79%) (p&amp;lt;.001). AML cases included 43% vs 30% secondary AML (sAML) in STAG2m vs PHF6m AML. Among STAG2m and PHF6m MN, 17% of each were tMN. Cytogenetic abnormalities were more common in PHF6m MN (50% vs 31%, p=.005). The median bone marrow (BM) blasts count among STAG2m MN was 7% vs 4% in PHF6m MN (p=.03). Genetic characteristics: STAG2m were nonsense, frameshift and splice site (54%, 36% and 11%). PHF6m were nonsense, frameshift, splice site, missense and start loss variant mutations (44%, 33%, 12%, 10% and 1%). The median variant allele frequency (VAF) of STAG2m MN was 50% compared to 32% in PHF6m MN (p=.008). Co-mutations: The median number of co-mutations was 3 in STAG2m and 4 in PHF6m MN (p=.04). The most common were TET2m (37% in STAG2m MN vs 45% in PHF6m MN), RUNX1m (31% in both), SRSF2m (39% vs 20%), ASXL1m (66% vs 38%), BCORm (19% vs 6%), U2AF1m (13% vs 14%) and IDH2m (18% vs 7%). ASXL1m, SRSF2m, BCORm, IDH2m and SF3B1m were more common among STAG2m MN (p=&amp;lt;.001, .003, .006, .02, .09). JAK2m, IDH1m are more common among PHF6m MN (p=.02, .06). Survival: Of STAG2m and PHF6m MN, 70% and 72% of patients received treatment. HSCT was performed in 23 (24%) and 23 (21%) of STAG2m and PHF6m patients, including AML (n=9, n=10), MDS (n=12, n=8), MDS/MPN (n=2, n=2). OS among STAG2m and PHF6m MN was 20.5 and 22.1 months, respectively. OS among AML cases was 13.5 vs 21 months (p=.6) in STAG2m vs PHF6m, was NR vs 22 months (p=.4) in MDS, 11.7 vs 17.6 months in MDS/MPN (p=.4), and 10.4 vs 27.4 months (p=.5) in MPN. There was no difference between males and females in either STAG2m or PHF6m MN. HSCT led to longer OS among both STAG2m (NR vs 19.9 months, p=.01) and PHF6m MN patients (NR vs 17.6 months, p=.07). Among AML patients, HSCT did not significantly impact OS (18 vs 9.6 months, p=.3 and 25.1 vs 21 months, p=.2, in STAG2m and PHF6m). HSCT improved OS in STAG2m MDS (NR vs 20.5 months, p=.03). In PHF6m MDS, OS was 22.1 vs 13.1 months in HSCT vs non-HSCT (p=.3). CONCLUSION: STAG2m and PHF6m are 2 X-linked mutations that occur in MN. Both commonly occur in elderly males. MDS was the most common diagnosis in STAG2m MN. STAG2m co-occurred particularly with SRSF2m ASXL1m and BCORm, which are associated with poor prognosis. In our cohort, STAG2m AML carried a poorer prognosis than PHF6m AML. Our study confirms the ELN2022 AML risk stratification. MDS risk classification and OS did not differ between STAG2m and PHF6m in our cohort. A larger cohort is required to confirm our findings and may provide stronger validation.

What Factors Predict the Development of Neurologic Deficits Following Resection of Intramedullary Spinal Cord Tumors: A Multi-Center Study

Intramedullary spinal cord tumors are challenging to resect, and their postoperative neurological outcomes are often difficult to predict, with few studies assessing this outcome. We reviewed the medical records of all patients surgically treated for Intramedullary spinal cord tumors at our multisite tertiary care institution (Mayo Clinic Arizona, Mayo Clinic Florida, Mayo Clinic Rochester) between June 2002 and May 2020. Variables that were significant in the univariate analyses were included in a multivariate logistic regression. "MissForest" operating on the Random Forest algorithm, was used for data imputation, and K-prototype was used for data clustering. Heatmaps were added to show correlations between postoperative neurological deficit and all other included variables. Shapley Additive exPlanations were implemented to understand each feature's importance. Our query resulted in 315 patients, with 160 meeting the inclusion criteria. There were 53 patients with astrocytoma, 66 with ependymoma, and 41 with hemangioblastoma. The mean age (standard deviation) was 42.3 (17.5), and 48.1% of patients were women (n= 77/160). Multivariate analysis revealed that pathologic grade >3 (OR=1.55; CI=[0.67, 3.58], P= 0.046 predicted a new neurological deficit. Random Forest algorithm (supervised machine learning) found age, use of neuromonitoring, histology of the tumor, performing a midline myelotomy, and tumor location to be the most important predictors of new postoperative neurological deficits. Tumor grade/histology, age, use of neuromonitoring, and myelotomy type appeared to be most predictive of postoperative neurological deficits. These results can be used to better inform patients of perioperative risk.

Utilization of the medical oncology pager and call center: Characterizing forgotten pillars of telemedicine in the digital era.

518 Background: Oncology has entered the digital era, accompanied by changes in patient interactions and expectations involving telemedicine. While much emphasis is appropriately placed on digital interactions with patients, little is known about modern non-digital interactions with patients in oncology practices. Methods: We analyzed Medical Oncology Pager (MOP) data from 7/1/18 – 4/14/23, during which patients had access to the electronic health record and messaging capabilities. The MOP for Mayo Clinic (Rochester) is covered by the medical oncology fellows, including after hours (6PM – 7AM). It covers consults and direct patient calls after hours and during weekends, in addition to critical results back up and inpatient oncology matters at all times. We also analyzed Medical Oncology Call Center (MOCC) data since 6/1/22, which takes inbound patient calls during working hours (7AM – 6PM) and is staffed by appointment office employees. Results: The MOP received a total of 17,679 pages during the analyzed period for a mean of 10.1 pages per day. Of these, 6,319 pages occurred after hours. The most after-hours pages were received on Fridays (n=1,091) and the least on Sundays (n=701); of those years with fully available data, 2022 had the highest volume (n=1,405) (Table 1). When comparing the MOP activity pre-pandemic (7/1/18 – 3/10/20) and intra-pandemic (3/11/20 – 4/14/23), the mean number of after-hours pages per day was relatively stable with 3.47 pre-pandemic and 3.69 intra-pandemic. Since 6/1/22, the MOCC has averaged 6,464 inbound calls per month during working hours, each of which had an average talk time of approximately five minutes. The majority of inbound calls occur on Monday mornings between 9 – 11AM, with over 6,500 recorded throughout the previous year. Conclusions: Telemedicine is multi-faceted, comprised of both digital and non-digital patient interactions. We show that many oncology patients utilize telephone communication with the healthcare system despite increased availability of digital capabilities. These data have implications for addressing the digital divide for those with limited digital access, serving older patient populations unfamiliar with digital technologies, healthcare navigation, trainee responsibilities, and resource allocation. Further work and standardization in non-digital telemedicine is necessary as it remains a pillar of modern healthcare delivery and oncology practices.[Table: see text]

Tumor Characteristics of Bilateral Breast Cancer Compared with Unilateral Breast Cancer.

Bilateral breast cancer (BC) has an incidence of 1 to 3 %. This study aimed to describe the clinicopathologic characteristics and management of bilateral BC, estimate disease-free survival (DFS), and compare DFS with unilateral BC. A retrospective analysis was performed for patients who hadbilateral invasive BC or unilateral invasive BC and contralateral ductal carcinoma in situ (DCIS) treated at Mayo Clinic Rochester from 2008 to 2022. A 4:1 matched cohort of patients with unilateral invasive BC was used for comparison. The groups were compared using Wilcoxon rank-sum or chi-square tests. Disease-free survival was analyzed using the Kaplan-Meier method and log-rank test, with Cox proportional hazards regression used for multivariable analysis. The study identified 278 cases of bilateral breast cancer (177 cases of bilateral invasive cancer and 101 cases of unilateral invasive cancer with contralateral DCIS), representing 4.1 % of invasive BCs. Biologic subtype was concordant between sides in 79.8 % of the patients. Initial surgery was bilateral mastectomy for 76.6 %, bilateral lumpectomy for 20.5 %, and unilateral mastectomy with unilateral lumpectomy for 2.9 % of the patients. Pathogenic variants in breast cancer predisposition genes were present in 21.7 % of those tested. The patients who had bilateral BC presented with a higher cT category than the patients who had unilateral BC (p = 0.02), and a higher proportion presented with ILC (17.3 % vs 10.9 %; p = 0.004), estrogen receptor-positive (ER+) disease (89.2 % vs 84.2 %; p = 0.04), multicentric/multifocal disease (37.1 % vs 24.3 %; p < 0.001), breast cancer pathogenic variant (21.7 % vs 12.4 %; p = 0.02), and palpable presentation (48.2 % vs 40.8 %; p = 0.03). The patients with bilateral BC showed DFS similar to that for the unilateral BC cohort (p = 0.71). Bilateral BCs most commonly are biologically concordant between sides. Bilateral BC presented more commonly with larger tumors, lobular histology, ER+ status, multicentricity or multifocality, pathogenic variant, and palpable disease. Bilateral BC is not associated with worse DFS than unilateral BC.

Conceptualization of Remote Patient Monitoring Program for Patients with Complex Medical Illness on Hospital Dismissal

ObjectiveTo describe the creation of a scalable framework for a Remote Patient Monitoring (RPM) program tied to a large medical practice. Patients and MethodsIn July 2020, at Mayo Clinic Rochester, we initiated the process to combine human-centered design, health systems engineering, and clinical expertise to develop and refine RPM programs and explore new medical conditions where RPM could be beneficial. We report on the creation of the overarching RPM program, the development of a hybrid nursing model, the technology used for each population, and the lessons learned throughout the process. ResultsFour pilot programs for hospitalized patients with cirrhosis, acute kidney injury (AKI), post-pancreatectomy, and post-gastroenterology (GI) procedures were launched. The 4 programs enrolled a range from 0 patients (post-GI procedures) to 91 patients over 5 months (AKI) for RPM programs ranging from 30 days to 96.5 days in average duration. Three of the programs continue enrollment (cirrhosis, AKI, and post-pancreatectomy), and one program was discontinued. ConclusionRPM can uniquely facilitate the transition from hospital to home, decrease hospital length of stay, and optimize hospital capacity and staffing resources in select scenarios. To achieve positive results at the health care system level, RPM interventions require a change in the model of care. However, not all care models or medical conditions lend themselves to RPM, which should be explored in pilot testing.