Mayo Clinic Rochester Research Articles

The Component Structure of the Dizziness Handicap Inventory (DHI): A Reappraisal.

The Dizziness Handicap Inventory (DHI) is a 25-item self-report questionnaire developed to measure the disabling and handicapping impact of dizziness. The present investigation was conducted in an effort to re-assess the factor structure of the DHI. Retrospective study. Tertiary care center. Subjects were 1,991 patients who were evaluated in the Mayo Clinic-Rochester Vestibular and Balance Laboratory. Exploratory factor analysis: an exploratory bifactor analysis (EFA) with bifactor rotation was used to analyze a random sample of 999 patients. Analyses were used to determine the dominance of the general factor (i.e., total score) relative to the group factor (i.e., subscales). Confirmatory factor analysis: a confirmatory bifactor graded response model was fit with appropriate item-to-group relationships that was discovered by our exploratory analyses. To validate the bifactor model that was identified with the exploratory analyses, a bifactor model with three grouping factors (i.e., Physical manifestations, Catastrophic impact of dizziness, and the Emotional impact of dizziness) were fit to a different random sample of 992 patients using the new item-to-group factor specifications. In the confirmatory analyses, all items had a positive factor loading on the general factor. There were 14 items that loaded on the general factor only. The rest of the items (n = 11) loaded on both the general factor and one of three group factors. Conclusions of the study revealed several findings: 1) reporting the result as a total score (i.e., a single general factor) is warranted, and, 2) there is statistical support for the existence of three subscales representing: the Physical manifestations, Catastrophic impact, and Emotional impact of dizziness and vertigo.

Experience With a Research and Innovation Office to Support Laboratory Medicine and Pathology Research

Abstract Objectives Translational research in laboratory medicine and pathology is transforming health care based on recent quantum advances in omics technologies, computational science, and precision medicine. However, high-volume clinical settings where this research may be most effective often have significant constraints on faculty time that challenge productivity. The objective of this study was to assess our experience with a new resource designed to address this challenge. Methods In September 2016, we established the Research and Innovation Office (RIO) in the Department of Laboratory Medicine and Pathology, Mayo Clinic–Rochester. The goal was to provide infrastructure to unburden faculty from performing administrative, organizational, and operational tasks related to research. Over 30 months, we solicited faculty input into desired services, conducted surveys on utility and ease of use, and tracked metrics, including faculty participation, numbers of projects, and publications. Results Faculty members were highly satisfied with the range of services, ease of use, and service-oriented approach of RIO. Initial services included project organization, institutional process support (eg, IRB protocol management), biospecimen requests and handling, and data management. Based on early feedback, patient consenting, budget support, and manuscript assistance were added as additional services. Total RIO staff increased from 6 to 10 during in the first 30 months. Over this time, 97 of 160 faculty members (60%) utilized RIO services in over 1,000 discrete project requests. Annual departmental publications increased by 50% during this time. Conclusion Faculty time is a critical element for translational research productivity in laboratory medicine and pathology departments. Numerous tasks previously performed by faculty could be managed effectively by a team of research facilitators that unburdened constraints on research time and led to high levels of faculty engagement, satisfaction, and productivity. This model may promote advances in transformative laboratory medicine and pathology research in high-volume clinical settings.

Tumor-Infiltrating Lymphocytes and Programmed Death-Ligand 1 Expression in Salivary Duct Carcinoma

Abstract Objectives Salivary duct carcinoma is a rare high-grade salivary gland tumor, sharing common features with invasive ductal carcinoma of the breast—particularly apocrine type. Increased density of tumor-infiltrating lymphocytes (TILs) is a favorable prognostic factor in many solid tumors and has been correlated with elevated expression of programmed death-ligand 1 (PD-L1), a targetable molecule. We investigated the prognostic role of TILs and PD-L1 expression in salivary duct carcinoma. Methods Clinical records and archived surgical pathology material were evaluated from 28 patients with a diagnosis of salivary duct carcinoma at Mayo Clinic Rochester (between 1961 and 2007). TILs were evaluated on hematoxylin and eosin–stained slides and reported as continuous variables. Immunohistochemistry for PD-L1 (clone 22C3) was performed on unstained slides and evaluated using the Combined Positive Score (CPS). Fisher’s exact test was used to assess frequency distribution differences. Log-rank test and Cox proportional hazards model were used to assess the impact of the variables on survival. Results Twenty-eight patients had salivary duct carcinoma (age range 35-87, mean 61), and follow-up averaged 60 months (range 6-252 months). At the end of the follow-up period, 22 patients (79%) had died of salivary duct carcinoma, while remaining patients were alive (4.14%) or had died of other causes (2.7%). For the entire follow-up period, levels of TILs of 40% or more were associated with favorable overall survival (log-rank test, P = .01) and were predictors of better survival in univariate analysis (hazard ratio: 0.18, P = .02). PD-L1 expression was not significantly different between the high and low TIL groups (Fisher’s exact test, P = .67). Survival analysis regarding PD-L1 expression did not yield statistically significant results (log-rank test, P = .74; hazard ratio: 0.87, P = .74). Conclusion High TIL levels, but not PD-L1 expression as determined using the CPS, predict better survival in patients with salivary duct carcinoma.

Improving Patient Value Through Cross-Country Collaboration

Abstract Introduction Lymph2Cx lymphoma cell-of-origin assay (LM2CX) was developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) to better categorize diffuse large B-cell lymphoma (DLBCL). NanoString has licensed the assay and is currently pursuing FDA approval. In the meantime, the test is offered exclusively as a lab-developed test (LDT) by the Mayo Clinic Molecular Diagnostics–Arizona Lab (MDAZL) to Mayo Clinic Enterprise patients. In order to comply with these restrictions, the normal workflow for Mayo Clinic Rochester has been modified as cases are sent to Arizona. Rochester consultants order LM2CX using their local laboratory information system (LIS). Slides are prepared by Rochester histology and then shipped to Arizona, where they are entered into the Arizona LIS and processed. In July 2018, we discovered numerous cases that were ordered but not shipped. Because this step took place at the LIS transition between Arizona and Rochester, it was not detected immediately. Methods Allied Health Staff (AHS) colleagues in Rochester and Arizona had the unique opportunity to collaborate. After Arizona AHS identified the problem, they reached out to the Rochester pathology reporting specialists (PRSs) and began a joint improvement project. Together, we were able to measure the impact of the problem, with Arizona auditing digitally, while Rochester audited physical cases. We found 29% of the cases were handled improperly over a 6-month time period. In order to eliminate the gap, Rochester implemented several improvements, including training, tagging all LM2CX cases, and huddle discussions, while Arizona AHS monitored the process digitally. Results Since implementation of improvements, we have had zero defects. Modifications to AHS/consultant training in Rochester will ensure continued success. Conclusions This intervention illustrates the importance of strong collaborations in order to quickly respond to testing issues and provide the greatest value to patients.

Hemodynamic profiles following digoxin use in patients with sepsis in the ICU

PurposeTo explore the impact of digoxin on hemodynamic parameters in patients with sepsis and tachycardia admitted to the intensive care unit. Materials and methodsRetrospective review of adult patients admitted to the medical and mixed ICU at Mayo Clinic Rochester, Minnesota from March 2008 to February 2018, initiated on digoxin within 24 h of ICU stay. Hemodynamic parameters were reviewed before digoxin administration and at 6, 12 and 24 h after. Adverse events including new onset conduction abnormalities or arrhythmias during the first 48 h after digoxin administration were reviewed by a critical care cardiologist. ResultsStudy included 180 patients. We observed significant decrease in heart rate from 124 (115–138) beats/min 1 h before digoxin to 101 (87–117) 6 h after digoxin and 94 (84–112) 12 h after (p < .01). Median systolic blood pressure increased from 100 (91–112) mm Hg 1 h before to 110 (100−122) (p < .01) and 111 (103–124) at 6 and 12 h respectively after digoxin. ConclusionsEarly digoxin administration in patients with sepsis and tachycardia is uncommon but associated with improvements of hemodynamic parameters. These preliminary results will help formulate future hypotheses for focused trials on utility, efficacy and safety of digoxin in sepsis.

Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis.

Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.

The Practice of Overlapping Colorectal Operations in a Tertiary Care Center Is Safe

Determine the safety of overlapping surgery in a tertiary care colorectal surgery practice. Although overlapping surgery is common in academic centers, reports on outcomes of this practice are limited. The primary aim of this study was to investigate the safety of overlapping surgery in a dedicated tertiary care academic colorectal practice by comparing groups of patients who did or did not have their surgery performed in an overlapping fashion. Retrospective review of 1270 colorectal patients undergoing inpatient colorectal surgery at our institution. Eligible participants were all patients undergoing elective inpatient colorectal surgery by one of the colorectal surgeons at the Mayo Clinic Rochester between January 1, 2012 and December 31, 2015. Patients under the age of 18 or who underwent an emergent procedure were excluded. Data were abstracted using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP) database. Additionally, each subject's chart was reviewed and further abstracted. The safety of overlapping surgery on outcomes was assessed using multiple multivariable models. One thousand two hundred seventy patients were included in the study cohort of whom 50.7% were female and the average age was 55.4 years. Overlapping surgery occurred in 576 patients (45%). There were no significant differences in demographic, surgical indications, procedures, or operative complexity between patients undergoing overlapping surgery and those who did not. Overall adverse events were significantly less likely in patients undergoing overlapping surgery compared with those who did not (18.4% vs 23.6%, P = 0.02). We found that overlapping surgery was associated with significantly less adverse events compared with patients not undergoing overlapping surgery using a model that controlled for the effect of the individual surgeon (OR 0.7, 95% CI 0.6 - 0.96; P = .02) and a multivariable propensity score (OR 0.7, 95% CI 0.5- 0.9; P = 01). Overlapping surgery in a tertiary care colorectal practice is safe and not associated with adverse patient outcomes.

FDG PET Positive Cardiac Amyloidosis

Background Cardiac positron emission tomography (PET) is routinely utilized to diagnose cardiac sarcoidosis, but may be positive in other cardiac conditions that result in myocardial inflammation. ATTR cardiac amyloidosis, an infiltrative disease that causes atrial arrhythmias and heart failure, is not typically thought to present with an inflammatory process. However, we observed four cases in which 18F-flurodeoxyglycose (FDG) PET scan findings were suspicious for cardiac sarcoidosis, but right ventricular endomyocardial biopsy (RV EMB) pathology specimens revealed ATTR wild-type (ATTRwt) cardiac amyloidosis. Methods Retrospective chart review was performed on patients with a positive cardiac FDG PET scan who also had a concomitant diagnosis of ATTR cardiac amyloidosis at Mayo Clinic Rochester between January 1, 2000 and March 24, 2019. Results Four patients with clinical presentation suggestive of cardiac sarcoidosis had positive FDG PET scans but were found to have biopsy-proven ATTRwt cardiac amyloidosis. All four patients were male with an average age of 71 years (62, 75). Two patients presented with ventricular arrhythmias and had transthoracic echocardiograms that were not suggestive of cardiac amyloidosis. FDG PET scans of these two patients revealed myocardial FDG uptake, similar to what can be seen in cardiac sarcoidosis. Both patients underwent RV EMB, with pathology specimens and mass spectrometry revealing ATTRwt cardiac amyloidosis. One of these two patients had a positive nuclear 99mTechnetium-pyrophosphate (PYP) scan (H/Cl ratio 1.9) and the other had a negative PYP scan (H/CL 1.2). The third patient, with a history of biopsy proven pulmonary sarcoidosis, presented with atrial fibrillation and conduction abnormalities. FDG PET scan revealed myocardial perfusion defects and patchy FDG uptake, but RV EMB revealed ATTRwt cardiac amyloidosis. Nuclear PYP was positive (H/Cl ratio of 1.8). The fourth patient presented with intermittent high grade AV block and underwent pacemaker implantation. He later developed frequent monomorphic premature ventricular contractions. Cardiac FDG PET scan illustrated FDG uptake, but the concurrent CT trunk did not illustrate any FDG uptake suspicious for extra-cardiac sarcoidosis. RV EMB was consistent with ATTRwt cardiac amyloidosis, but PYP was negative. Discussion These findings suggest that inflammation could play a role in ATTR cardiac amyloidosis. We have previously seen inflammatory changes of lymphohistiocytic infiltration around areas of amyloid protein deposition on biopsy specimens in ATTR cardiac amyloidosis. The role of therapy targeted at stabilizing transthyretin versus immunosuppressive agents in this subgroup remains unclear.

Comparison of eVisit Management of Urinary Symptoms and Urinary Tract Infections with Standard Care.

Background: Urinary symptoms and urinary tract infections (UTIs) are common complaints for which women seek health care. Evolving modalities of care delivery have shifted management of these complaints from in-person face-to-face (F2F) visits, to nurse phone protocol management, and recently to online assessment via eVisit. While research has vetted the use of nurse phone protocol management, eVisit management outcomes have not been thoroughly studied. Purpose: To compare antibiotic prescribing, follow-up rates, and clinical outcomes between F2F visits at a retail clinic, nurse phone protocol encounters, and eVisits for the assessment and management of urinary symptoms and UTIs. Methods: A retrospective chart review of primary care empaneled patients at Mayo Clinic Rochester was conducted of females, 18 to 65 years old, who sought care for urinary symptoms via phone, eVisit, or F2F visit from August 1, 2016, through May 1, 2017. A total of 450 encounters, 150 from each of the 3 encounter types, were manually reviewed and compared for antibiotic prescribing rates, clinical outcomes, and 30-day follow-up rates. Results: Antibiotic prescribing rates for all three encounter types were similar. Referral for follow-up at initial encounter was more likely to be recommended from phone and eVisit encounters than F2F. No significant differences in follow-up rates or clinical outcomes were noted between the three encounter types. Conclusions: eVisits for urinary symptoms and UTI offer patients a convenient option for care without an increased use of antimicrobials, follow-up, or adverse clinical outcomes when compared with F2F visits or nurse-administered phone protocols.

Liver Transplantation Trends and Outcomes for Hereditary Hemorrhagic Telangiectasia in the United States.

Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States. Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT. Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure. Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.

P037 Medication therapy management is an effective tool to reduce office staff burden and optimize patient outcomes: A randomized pilot study

BACKGROUND: Medication Therapy Management (MTM) is a strategy for developing a variety of non-dispensing clinical pharmacy services to patients which aim to optimize therapeutic outcomes by identifying and resolving drug therapy problems. We conducted a pilot study to see if MTM could serve as a measurable value-add as demonstrated by improved outcomes for IBD injectable biologic patients and reduced disease management burden for clinicians and office staff. METHODS: Adult patients with either UC or CD prescribed new self-injectable biologic agents (adalimumab [ADA], certolizumab pegol [CTZ], golimumab [GOL], or ustekinumab [USTE]) were recruited from outpatient clinics at Mayo Clinic Rochester, Arizona, Florida or Health System. Exclusion criteria included prescriptions that were refills, patients with need for urgent hospitalization, pregnant patients, those without a reliable and confirmed shipping address or reliable telephone access, or patients residing outside of the United States. Patients were randomized to receive standard care or be enrolled in a collaborative, high-touch MTM program administered by Curant Health PharmD's. Patients randomized to MTM were further stratified to either having medications filled by Curant Health or specialty pharmacy as dictated by insurance plan. Patients receiving standard care were managed as per discretion of the treating physician. Patients receiving MTM arms were contacted per a defined protocol with calls at specified time points. The primary outcome of interest was number of unsolicited calls/messages from patients to practice sites during the study time period along with total time spent on the managing of those messages either electronically or via telephone. Secondary outcomes of interest included medication adherence as defined by percent of patients with a score of &gt;6 at week 24 (MMAS-8) and disease activity as measured by relevant disease indices. RESULTS: 20 patients were randomized to MTM and 19 to standard care. There was no difference in median age or sex distribution among groups. The majority of patients were started on ADA, 1 CTZ and 1 USTE. One patient was enrolled twice with different medications to the standard group. Nine MTM patients required additional support to optimize therapy with 1 patient requiring 6 additional calls. The majority of calls involved injection administration, how to treat injection site reaction, pain and misfiring. The number of unsolicited calls overall in the MTM arm were significantly higher than standard care: 3 vs 1 (P &lt; 0.05). The overall adherence to medication at week 24 was significantly higher with MTM; scores ranged from 7.5–8 vs 5.5–6 in the standard care group (P &lt; 0.05). The median disease score of the MTM group also improved significantly for both diseases by &gt;50% at week 24 for 13/20 patients compared with 10/19 for standard group. CONCLUSION(S): Patients in the high-touch, collaborative MTM arm received additional engagement as evidenced by the significant increase in unsolicited patient calls. MTM patients also showed improved adherence and improved disease outcomes to injectable therapy. This suggests that MTM services are an effective mechanism to relieve burden of office staff while improving patient care.

Utilization Review of Paraneoplastic Neurological Syndrome Antibody Screening Panels: Experience at a Tertiary Academic Health Center

Pathology departments play a pivotal role in managing laboratory test utilization in healthcare, and inappropriate resource deployment can contribute to unnecessary healthcare costs. Here we share our experience reviewing a send-out test and implementing a utilization strategy. Antibody testing is often considered in the workup for patients with unexplained paraneoplastic syndrome-like neurological presentations. It has been unclear how helpful these antibody tests are. The goal of study is to evaluate diagnostic utility of antibody screening panel results in patients suspicious for paraneoplastic neurological syndrome and possibly underlying occult malignancy. We retrospectively reviewed the paraneoplastic neurological syndrome antibody test results. The positive predictive value and negative predictive value were calculated. The proportion of the antibody screening results were compared between groups with and without tumor with 2-sided χ2 test statistics. In total 348 panels were sent to 2 reference laboratories. From ARUP (Associated Regional and University Pathologists; Salt Lake City, Utah), 2 out of 232 screening panels yielded positive results (0.86%) and from the Mayo Clinic (Rochester, Minnesota), 26 out of 116 screening panels yielded positive results (22.4%). The overall positive predictive value was 3.57% (1/28) and the overall negative predictive value was 91.2% (292/320). There were no statistically significant differences between the antibody screening test results between the 2 groups with and without tumor. We found the diagnostic utility and yield for the paraneoplastic antibody panel to be low. Following a multidisciplinary team review of the study results, the pathology department has implemented several new utilization strategies.

An Approach to Addressing Trainee Burnout: Revising Fellow Shift Scheduling in the Intensive Care Unit

Introduction: Rotating shift patterns and night shifts are associated with fatigue and sleep deprivation, which in turn contribute to burnout. The aim of this quality improvement initiative at Mayo Clinic Rochester critical care fellowship programs was to implement a new critical care fellow shift schedule in the medical intensive care unit while evaluating the impact on self-reported burnout scores. Materials and Methods: Focus groups of fellows weighed pros and cons of the existing schedule and selected a revision of the schedule in which night shifts were grouped into blocks with limited frequency and incorporated a recovery period. Baseline self-reported burnout amongst critical care fellows was assessed using an abbreviated Maslach burnout inventory (MBI) screening questionnaire and re-evaluated at the end of the implementation period. Results: At baseline, 33 of 45 (73%) fellows responded to a survey with the abbreviated Maslach Burnout Index questionnaire. Median (IQR) scores for each of the domains were 10 (6-12) emotional exhaustion, 3 (1-9) depersonalization, and 15 (13-17) personal accomplishment. For the post-intervention survey, 17 out of 24 (71%) responded. The median (IQR) score for critical care internal medicine and pulmonary and critical care fellows was 7 (4-11), P=.06 and 9 (7-11), P=0.5 for emotional exhaustion; 3 (0-6), P=.07 and 5 (0-11), P=1.0 for depersonalization score; and 16 (11-17), P=.31 and 15 (12-17), P=.75 for personal accomplishment score. Discussion: Reducing the number of day-night rotations, incorporating a scheduled recovery period, and limiting the number of recurrent consecutive nights resulted in a trend towards improvement of self-reported burnout amongst critical care fellows.

Mechanism and Risk Factors for Death in Adults With Tetralogy of Fallot

One of the goals of lifelong care in adults with tetralogy of Fallot (TOF) is early identification and treatment of patients at high risk for adverse events. Clinical risk stratification tools are critical for achieving this goal. We reviewed the Mayo Adult Congenital Heart Disease database and identified 465 TOF patients (age 37 ± 14 years, men 223 [48%]) seen at Mayo Clinic Rochester between 1990 and 2017. The aim was to determine the risk factors for death and/or heart transplant through a comprehensive analysis of 8 groups of variables (demographics, co-morbidities, medications, heart rhythm, echocardiography, cardiac magnetic resonance imaging, cardiac catheterization, and cardiopulmonary exercise test data) using univariable and multivariable Cox proportional hazard models. The end point of death and/or transplant occurred in 57 (12%) patients during a follow-up of 13.6 ± 8.2 years, yielding an event rate of 0.9% per year. Independent risk factors were age >42 years, atrial fibrillation, ≥moderate QRS fragmentation, left ventricular ejection fraction <50%, right ventricular end-diastolic pressure >16 mm Hg, and left ventricle end-diastolic pressure >16 mm Hg. There is nearly a twofold increase in the risk of death and/or transplant per unit increase in number of risk factors (hazard ratio 1.92, 95% confidence interval 1.62 to 2.27, p <0.001). In conclusion, the current study provides risk stratification indices based on a comprehensive risk model of all clinical variables in an unselected TOF population. Further studies are required to determine whether interventions targeted at modifying these risk factors will alter the annual event rate.

PF484 MARKERS ASSOCIATED WITH SHORT SURVIVAL IN PATIENTS WITH WALDENSTRÖM MACROGLOBULINEMIA

Background:Waldenström Macroglobulinemia (WM) is a rare, indolent B‐cell lymphoplasmacytic malignancy. Patient outcomes are highly heterogeneous, with a proportion of patients surviving less than 5 years (short survivors) and another proportion that survive longer than 10 years. The laboratory parameters in the currently used International Prognostic Scoring System for WM (IPSSWM) include hemoglobin, serum IgM, platelet count, and serum β2‐microglobulin.Aims:We aim to identify unique patient characteristics and prognostic features associated with short survival in WM.Methods:The medical records of patients with active WM that were diagnosed at Mayo Clinic Rochester, Arizona, and Florida between January 1st, 1996 and December 31st, 2013 were reviewed. The patients with smoldering WM were excluded. Cohorts of patients who either survived ≤ 5 years (Short Survival Group) or those with an overall survival (OS) ≥ 10 years (Long Survival Group) from the diagnosis of active disease were compared. Survivors with a follow‐up of ≤ 5 years were not included in the analyses. Two‐sided Wilcoxon rank sum test and Chi square/Fisher's exact test were used to compare the continuous and categorical variables, respectively. The variables that were statistically significant on univariate analysis (P &lt; 0.05) were included in a multivariate logisitic regression analysis.Results:Of 893 consecutively seen WM patients (median follow‐up of 9 years [95% CI 8.4–9.7]), we identified 387 patients who could be categorized into either the Short Survival Group (n = 171 patients, 44%) or the Long Survival Group (n = 216, 56%). The Short Survival Group had a median OS of 2.4 years (2.1–2.8) and median age at diagnosis of 73 years (42–93), while the Long Survival Group (n = 216, 56%) had a median OS of 18.9 years (16‐NR) and median age at diagnosis of 62 years (31–85). The baseline characteristics and significant findings between the two groups are listed in the Table. Parameters significant on univariate analysis included age &gt;65 years, albumin &lt; 3.5 g/dL, β2‐microglobulin &gt;3 μg/ml, and LDH &gt; upper limit of normal (ULN). On multivariate analysis, albumin &lt;3.5 g/dL and LDH &gt; ULN were independently associated with short survival. Among the Long Survivors, 60 (28%) patients survived 15 years or more.Summary/Conclusion:Lactate dehydrogenase above the ULN and serum albumin &lt;3.5 g/dL are independent biomarkers of short survival in WM. The MYD88 L265P status and the size of serum IgM are not prognostic in WM. Our data suggest the need for simplification of the current staging system with the use of widely available markers: serum albumin and lactate dehydrogenase.image

Long-Term Outcomes in Patients With Turner Syndrome: A 68-Year Follow-Up.

BackgroundTurner syndrome (TS) is the most common sex chromosome abnormality in women and is associated with increased morbidity and mortality. We describe long‐term outcomes in a large cohort of patients with TS.Methods and ResultsRetrospective review of patients with TS followed at Mayo Clinic Rochester from 1950 to 2017 was performed. Clinical, imaging, surgical, and genetic data were analyzed. Survival analysis was performed with the Kaplan–Meier method using age‐ and sex‐matched Olmsted County residents as the reference group. The study cohort comprised 317 patients with TS. Average age at diagnosis was 9 (range, 2–12) years, genetic testing was performed in 202 (64%), and pure monosomy X was present in 75 (37%). Congenital heart disease occurred in 131 (41%), with the most frequent lesions being bicuspid aortic valve (n=102, 32%) and coarctation of the aorta (n=43, 14%). Ascending aortic dilation was common, with mean aortic root size index 2 cm/m2, and aortic dissection occurred in 6 (2%) patients. The average follow‐up was 11 (range, 2–26) years, yielding 3898 patient‐years, and during this period 46 (14%) patients died; mean age at the time of death was 53±17 years. Patients with TS had reduced survival compared with the control group (82% versus 94% at 30 years; P<0.001), and the leading causes of death were cardiovascular disease, liver disease, and malignancy.ConclusionsPatients with TS have reduced survival compared with age‐matched controls, and cardiovascular disease is the major cause of death. Further studies are required to determine if targeted cardiovascular risk factor modification will result in improved survival in this population.

Combined effect of volumetric breast density and body mass index on breast cancer risk.

Breast density and body mass index (BMI) are used for breast cancer risk stratification. We evaluate whether the positive association between volumetric breast density and breast cancer risk is strengthened with increasing BMI. The San Francisco Mammography Registry and Mayo Clinic Rochester identified 781 premenopausal and 1850 postmenopausal women with breast cancer diagnosed between 2007 and 2015 that had a screening digital mammogram at least 6months prior to diagnosis. Up to three controls (N = 3535) were matched per case on age, race, date, mammography machine, and state. Volumetric percent density (VPD) and dense volume (DV) were measured with Volpara™. Breast cancer risk was assessed with logistic regression stratified by menopause status. Multiplicative interaction tests assessed whether the association of density measures was differential by BMI categories. The increased risk of breast cancer associated with VPD was strengthened with higher BMI for both premenopausal (pinteraction = 0.01) and postmenopausal (pinteraction = 0.0003) women. For BMI < 25, 25-30, and ≥ 30kg/m2, ORs for breast cancer for a 1SD increase in VPD were 1.24, 1.65, and 1.97 for premenopausal, and 1.20, 1.55, and 2.25 for postmenopausal women, respectively. ORs for breast cancer for a 1SD increase in DV were 1.39, 1.33, and 1.51 for premenopausal (pinteraction = 0.58), and 1.31, 1.34, and 1.65 (pinteraction = 0.03) for postmenopausal women for BMI < 25, 25-30 and ≥ 30kg/m2, respectively. The effect of volumetric percent density on breast cancer risk is strongest in overweight and obese women. These associations have clinical relevance for informing prevention strategies.

Outcomes of laparoscopic and open CAPD catheter placement: A single-center experience

BackgroundContinuous Ambulatory Peritoneal Dialysis (CAPD) catheter placement is typically a straightforward surgical procedure performed on chronically ill patients with end-stage renal disease (ESRD). Post-operative outcomes and reoperative rates vary greatly in the medical literature. We report our experience using both minimally invasive and open techniques in placing CAPD catheters and offer our surgical outcomes. MethodsThis study is an IRB-approved, retrospective review (2005–2018) of all patients undergoing CAPD catheter placement at Mayo Clinic-Rochester. Analysis focused on specific patient outcomes, including early (<30 days) versus late (≥30 days) complication and reoperation rates. ResultsA total of 173 patients with ESRD (mean ASA score = 3.1) underwent laparoscopic (n = 22) and open (n = 151) CAPD catheter placement (mean follow-up = 309 days; range: 1–3497 days). The total index operation complication rate was 41%. The total index reoperation rate was 37% and was similar in open and laparoscopic approaches. CAPD catheters malfunctioned in 19 patients (11% of total) and each underwent reoperation. CAPD catheter infections occurred in 30 patients (17% of total), and 24 required reoperation; 6 patients were treated successfully with antibiotics. CAPD catheter migrations occurred in 21 patients (12% of total) and all underwent reoperation. ConclusionAlthough CAPD catheter placements in patients with ESRD are technically easy to accomplish, the long term outcomes suggest as many as one in three patients will struggle with catheter function or infection. This study has led to changes in our technical CAPD catheter placement procedures, as well as the post-operative patient care algorithm.

Metaplastic breast cancer has a poor response to neoadjuvant systemic therapy.

Metaplastic breast cancer (MetaBC) is a rare breast cancer subtype poorly responsive to systemic therapy in the metastatic setting with high recurrence rates in the adjuvant setting. However, limited data exist regarding response to neoadjuvant chemotherapy (NAC). We performed a single institutional study to assess the clinical and pathological complete response rates (pCR) of MetaBC to NAC. Mayo Clinic Rochester patients with MetaBC treated with NAC were identified using the institutional medical index. Patient demographics, tumor characteristics, chemotherapy treatment, clinical and pathological response, and long-term outcomes were reviewed. Pathologic response was assessed by direct pathology review (n = 14) or review of outside surgical and pathology reports (n = 4). Women with MetaBC (n = 18) received NAC from January 1991 to June 2014. The mean age was 50years (range 33-79) with a mean tumor size of 5.1cm (range 2.3-11cm) and 6/18 had pathologically confirmed lymph nodes prior to surgery. The majority (13/18; 72%) were estrogen receptor (ER), progesterone receptor (PR) and HER-2 negative (TNBC), and 1/18 (5.5%) was HER-2 positive. Five had BRCA testing and 2/5 were BRCA-2 positive. The chemotherapy regimens included anthracycline/cyclophosphamide (AC) (n = 1), AC/taxane (n = 3), AC/taxane/platinum (n = 8), taxane/platinum-based regimens (n = 4), taxane/cyclophosphamide (n = 1) and taxane/trastuzumab (n = 1). Five of 18 (28%) progressed on initial treatment including two who developed metastatic disease during NAC. The overall pCR rate was 2/18 (11%). MetaBC is poorly responsive to NAC, with a pCR rate (11%), that is lower than expected in a predominantly TNBC cohort. MetaBC patients should be considered for clinical trials testing new NAC regimens and in the absence of clinical trial enrollment, MetaBC patients with resectable disease should proceed directly to definitive operative management.

Sex Differences in Tolerability to Anti-Programmed Cell Death Protein 1 Therapy in Patients with Metastatic Melanoma and Non-Small Cell Lung Cancer: Are We All Equal?

Immune-related adverse events (irAEs) have emerged as a serious clinical issue in the use of immune checkpoint inhibitors (ICIs). Risk factors for irAEs remain controversial. Therefore, we studied sex differences in irAEs in patients treated with anti-programmed cell death protein 1 (PD-1) therapy. All patients with metastatic melanoma and non-small cell lung cancer (NSCLC) treated with anti-PD-1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Kaplan-Meier method and log-rank test was used for time-to-event analysis. In 245 patients with metastatic melanoma, premenopausal women were more likely to experience irAEs (all grades) compared with postmenopausal women and men (67% vs. 60% vs. 46%), primarily because of an increase in endocrinopathies (33% vs. 12% vs. 10%, respectively). In patients with NSCLC (231 patients), women (all ages) were also more likely to develop irAEs of all grades (48% vs. 31%). Women with NSCLC were more likely to develop pneumonitis (11% vs. 4%) and endocrinopathies (14% vs. 5%). No differences in grade ≥3 toxicities were seen across sexes in both cohorts, but women were more likely to receive systemic steroids for the treatment of irAEs compared with men. Better progression-free-survival was observed in women with NSCLC and irAEs (10 months vs. 3.3 months) compared with women without irAEs. Women with metastatic melanoma and NSCLC are more likely to experience irAEs compared with men. We also observed differences between sexes in the frequency of certain irAEs. Larger studies are needed to investigate the mechanisms underlying these associations. The results of this study suggest that women may be at a higher risk for immune-related adverse events (irAEs) compared with men when treated with anti-programmed cell death protein 1 therapy. In addition, women were more likely to develop certain irAEs, including endocrinopathies and pneumonitis. Close follow-up of women undergoing treatment with immune checkpoint inhibitors will allow clinicians to diagnose these treatment-related complications early, potentially reducing their associated morbidity and mortality. In addition, a possible association between irAEs and response to therapy was observed.