Mayo Clinic Rochester Research Articles

Abstract A120: Sex differences in tolerability and response to immune checkpoint inhibitors in non-small cell lung cancer patients

Abstract Background: Sex differences in non-small cell lung cancer (NSCLC) outcomes have been described. Immune-related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors (ICI). Risk factors for IRAEs and their association with response to therapy remain controversial. Sex differences in innate and adaptive immune responses have been observed but the association of these differences with IRAEs remains unclear. Therefore, we studied sex differences in IRAEs and their association with response to therapy. Methods: All patients with metastatic NSCLC treated with anti-PD1 and anti-PDL1 therapy at Mayo Clinic Rochester and Florida from 2015 to 2018 were reviewed. Patients receiving treatment at an outside facility with history autoimmune disorders or radiation-induced pneumonitis were excluded. Chi-square test was used to estimate differences in categorical data. Kaplan-Meier method was used for time-to-event analysis. Results: A total of 231 patients were identified; 120 (52%) were women and 111 (48%) were men. Baseline characteristics and ICI distribution were similar among groups. Women were more likely to experience IRAEs compared to men (48% vs. 31%, p<0.008). Among patients with IRAEs, women were more likely to be prescribed systemic steroids (63% vs. 41%, p<0.02). On the other hand, no significant differences were observed in the administration of intravenous steroids. Women were more likely to develop pneumonitis (23% vs. 12%, p<0.03) and arthralgias (17% vs. 3%, p<0.04). However, dermatologic toxicities (35% vs. 9%, p<0.002) were more commonly seen in men. In 17% of women the ICI was discontinued due to toxicity (men 7%). Besides sex, no other clinical characteristic was associated with increased IRAEs. Women with IRAEs were more likely to have a radiographic response compared with women without IRAEs (78% vs. 23%, p<0.0001), although this was not observed in men (37% vs. 26%, p>0.22). Better PFS was observed in women with IRAEs (10 months vs. 3.3 months, p<0.0006) compared to women without IRAEs. Conclusions: Women with metastatic NSCLC are more likely to experience IRAEs compared to men. We also observed sex differences in the frequency of certain IRAEs. In addition, an association between IRAEs and response to therapy was observed in women. Larger studies are needed to investigate the mechanisms underlying these associations. Citation Format: Narjust Duma, Abdel-Ghani Azzouqa, Siddhartha Yadav, Kahterine Hoversten, Clay Reed, Andrea Sitek, Elizabeth Enninga, Jonas Paludo, Lisa Kottschade, Aaron Mansfield, Rami Manochakian, Roxana Dronca, Alex Adjei. Sex differences in tolerability and response to immune checkpoint inhibitors in non-small cell lung cancer patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr A120.

0738 Advance Taper of Antidepressants Prior to Multiple Sleep Latency Testing Increases the Number of Sleep-Onset Rapid Eye Movement Periods and Reduces Mean Sleep Latency

Abstract Introduction Patients presenting with excessive sleepiness are frequently on antidepressant medication(s). While practice parameters recommend discontinuation of antidepressants prior to multiple sleep latency testing (MSLT), data examining the impact of tapering these medications on MSLT results are limited. Methods Adult patients who underwent MSLT at Mayo Clinic Rochester, Minnesota, between 2014-2018 were included. Clinical and demographic characteristics, medications, including use of rapid eye movement suppressing antidepressants (REMS-AD) at assessment and during testing, actigraphy and polysomnography data were manually abstracted. The difference in number of sleep-onset rapid eye movement periods (SOREMS), proportion with ≥2 SOREMS and mean sleep latency (MSL) in patients who were on REMS-AD and discontinued prior to testing versus those who remained on REMS-AD were examined. At our center, all antidepressants are discontinued 2 weeks prior to MSLT wherever feasible; fluoxetine is stopped 4 weeks prior. Regression analyses accounting for demographic, clinical and other medication-related confounders were performed. Results A total of 502 patients (age=38.18±15.90 years; 67% female) underwent MSLT; 178 (35%) were on REMS-AD at the time of assessment. REMS-AD were discontinued prior to testing in 121/178 (70%) patients. Patients tapered off REMS-AD were more likely to have ≥2 SOREMS (OR-12.20; 95%CI=1.60-92.94) compared to patients who remained on REMS-AD at the time of the MSLT. They also had shorter MSL (8.77±0.46 vs 10.21±0.28; p>0.009) and higher odds of having ≥2 SOREMS (OR=2.22; 95%CI=1.23-3.98) compared to patients not on REMS-AD at initial assessment. These differences persisted after regression analyses accounting for confounders. Conclusion Patients who taper off REMS-AD prior to MSLT are more likely to demonstrate ≥2SOREMs and have a shorter MSL. Pending further prospective investigations, clinicians should preferably withdraw REMs-AD before an MSLT. If this is not done, the test interpretation should include a statement regarding the potential effect of the drugs on the results. Support None

Effect of antibiotic use prior to or concurrent with immune checkpoint inhibitors on outcomes in patients with Hodgkin lymphoma.

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

Comparing outcomes and costs among warfarin-sensitive patients versus warfarin-insensitive patients using The Right Drug, Right Dose, Right Time: Using genomic data to individualize treatment (RIGHT) 10K warfarin cohort.

Oral anticoagulant (OAC) therapy has been the main treatment approach for stroke prevention for decades. Warfarin is the most widely prescribed OAC in the United States, but is difficult to manage due to variability in dose requirements across individuals. Pharmacogenomics may mitigate risk concerns related to warfarin use by fostering the opportunity to facilitate individualized medicine approaches to warfarin treatment (e.g., genome-guided dosing). While various economic evaluations exist examining the cost-effectiveness of pharmacogenomics testing for warfarin, few observational studies exist to support these studies, with even fewer using genotype as the main exposure of interest. We examined a cohort of individuals initiating warfarin therapy between 2004 and 2017 and examined bleeding and cost outcomes for the year following initiation using Mayo Clinic’s billing and administrative data, as well the Mayo Clinic Rochester Cost Data Warehouse. Analyses included descriptive summaries, comparison of characteristics across exposure groups, reporting of crude outcomes, and multivariate analyses. We included N = 1,143 patients for analyses. Just over a third of our study population (34.9%) carried a warfarin-sensitive phenotype. Sensitive individuals differed in their baseline characteristics by being of older age and having a higher number of comorbid conditions; myocardial infarction, diabetes, and cancer in particular. The occurrence of bleeding events was not significantly different across exposure groups. No significant differences across exposure groups existed in either the likelihood of incurring all-cause healthcare costs or in the magnitude of those costs. Warfarin-sensitive individuals were no more likely to utilize cardiovascular-related healthcare services; however, they had lower total and inpatient cardiovascular-related costs compared to warfarin-insensitive patients. No significant differences existed in any other categories of costs. We found limited evidence that warfarin-sensitive individuals have different healthcare spending than warfarin-insensitive individuals. Additional real-world studies are needed to support the traditional economic evaluations currently existing in the literature.

Pulmonary Complications Secondary to Immune Checkpoint Inhibitors.

Background Immune checkpoint inhibitors (ICI) have changed the landscape in the treatment of a number of cancers. Immune-related adverse events (irAEs) have emerged as a serious clinical problem with the use of ICI. Methods All oncology patients diagnosed with pulmonary complications secondary to ICI at Mayo Clinic Rochester from January 1, 2012 to December 31, 2018 were reviewed. Demographics, comorbidities, smoking, and oncologic history were analyzed. Results A total of 10 patients developed pulmonary complications secondary to ICI. Seven patients were men (70%), and the median age at diagnosis was 61.5 (IQR 55.8-69.3) years. All patients had stage IV disease. Melanoma was the most common malignancy. Seven (70%) patients had a positive smoking history, and 6 (60%) were obese (BMI > 30). Most cases were grade 2 pneumonitis (70%). One patient with grade 4 pneumonitis required endotracheal intubation and a prolonged course of systemic corticosteroids (>30 days). Eight (80%) patients received prior radiation therapy. The median time from initiation of ICI to pneumonitis diagnosis was 3.5 months. Conclusion Melanoma was the most common malignancy, the majority of patients had grade 2 pneumonitis and required treatment with steroids, and all patients affected by ICI-related pneumonitis had stage IV malignancy. Potential risk factors included smoking history, prior radiotherapy, obesity, and advance stage at the time of ICI initiation. Extrapulmonary irAEs are common in patients with pneumonitis.

Perioperative and long-term outcomes of utilizing donation after circulatory death liver grafts with macrosteatosis: A multicenter analysis.

Given the potentially additive risk from using donor livers that are both steatotic and from a donation after circulatory death (DCD) donor, there is a paucity of data on the outcome of DCD liver transplantation (LT) utilizing livers with macrosteatosis. All DCD LT performed at Mayo Clinic-Florida, Mayo Clinic-Arizona, and Mayo Clinic-Rochester from 1999 to 2019 were included (N=714). Recipients of DCD LT were divided into 3 groups: those with moderate macrosteatosis (30%-60%), mild macrosteatosis (5%-30%), and no steatosis (<5%). Patients with moderate macrosteatosis had a higher rate of postreperfusion syndrome (PRS; 53.9% vs 26.2%; P=.002), postreperfusion cardiac arrest (7.7% vs 0.3%; P<.001), primary nonfunction (PNF; 7.7% vs 1.0%; P=.003), early allograft dysfunction (EAD; 70.8% vs 45.6% and 8.3%; P=.02), and acute kidney injury (AKI; 39.1% vs 19.4%; P=.02) than patients with no steatosis. No difference in any of the perioperative complications was seen between the mild macrosteatosis and the no steatosis groups except for the rate of EAD (56.8% vs 45.6%; P=.04). No difference in ischemic cholangiopathy (IC), vascular thrombosis/stenosis or graft, and patient survival was seen between the 3 groups. DCD donors with mild macrosteatosis<30% can be utilized with no increase in perioperative complications and similar patient and graft survival compared to DCD donors with no steatosis. When utilizing DCD donors with moderate macrosteatosis higher rates of PRS, PNF, postreperfusion cardiac arrest, EAD, and AKI should be anticipated.

Effect of initial infusion rates of fluid resuscitation on outcomes in patients with septic shock: a historical cohort study

BackgroundFluid resuscitation has become the cornerstone of early septic shock management, but the optimal fluid rate is still not well studied. The goal of this investigation is to examine the relationship between fluid resuscitation rate and septic shock resolution.MethodWe retrospectively studied adult (≥ 18 years) patients with septic shock, defined based on sepsis III definition, from January 1, 2006, through May 31, 2018, in the medical intensive care unit (MICU) of Mayo Clinic Rochester. The fluid resuscitation time was defined as the time required to infuse the initial fluid bolus of 30 ml/kg, based on the recommendations of the 2016 surviving sepsis campaign. The cohort was divided into four groups based on the average fluid rate (group 1 ≥ 0.5, group 2 0.25–0.49, group 3 0.17–0.24, and group 4 < 0.17 ml/kg/min). The primary outcome was the time to shock reversal. Multivariable regression analyses were conducted to account for potential confounders.ResultA total of 1052 patients met eligibility criteria and were included in the analysis. The time-to-shock reversal was significantly different among the groups (P < .001). Patients in group 1 who received fluid resuscitation at a faster rate had a shorter time to shock reversal (HR = 0.78; 95% CI 0.66–0.91; P = .01) when compared with group 4 with a median (IQR) time-to-shock reversal of 1.7 (1.5, 2.0) vs. 2.8 (2.6, 3.3) days, respectively. Using 0.25 ml/kg/min as cutoff, the higher fluid infusion rate was associated with a shorter time to shock reversal (HR = 1.22; 95% CI 1.06–1.41; P = .004) and with decreased odds of 28-day mortality (HR = 0.71; 95% CI 0.60–0.85; P < .001).ConclusionIn septic shock patients, initial fluid resuscitation rate of 0.25–0.50 ml/kg/min (i.e., completion of the initial 30 ml/kg IV fluid resuscitation within the first 2 h), may be associated with early shock reversal and lower 28-day mortality compared with slower rates of infusion.

Cardiovascular surgery in Turner syndrome - early outcome and long-term follow-up.

Cardiovascular disease is the leading cause of death in patients with Turner syndrome (TS), and cardiovascular surgery is frequently required for management of these patients. TS is associated with medical comorbidities than can complicate the care of this patient population. To describe the cardiovascular surgical outcomes of patients with TS. A retrospective case series was compiled of 51 consecutive TS patients who had at least one cardiovascular surgery at Mayo Clinic Rochester from 1977-2017. The baseline clinical data of these patients were reviewed including demographics, medical comorbidities, congenital heart disease history, and medications. Echocardiographic reports were analyzed in detail. Operative reports and surgical hospital courses were reviewed. Long-term mortality was determined using medical records and the Social Security Death Index. Survival analysis was performed with the Kaplan Meier method. The cohort comprised 51 TS patients, average age at the time of surgery at Mayo Clinic was 28 (8-41) years, and 23 (45%) patients were under the age of 18. At the time of first Mayo Clinic surgery, 18 (35%) patients had previously undergone cardiac surgery at another institution. The most common procedures were repair of aortic coarctation in 14 (28%) patients, aortic valve replacement in 6 (12%) patients, and composite aortic root/ascending aorta replacement in 7 (14%) patients, with 7 patients undergoing repair of more than one lesion. Aortic dissection required operative intervention in 5 patients. After initial Mayo Clinic surgery, subsequent operations were required in 6 (13%) patients. Average hospital length of stay was 6 ± 2 d. There were 4 (8%) early surgical deaths. Freedom from death was 97% and 89% at 10 and 20 years, and the freedom from reoperation was 93% and 81% at 10 and 20 years. Cardiovascular surgery is associated with 8% early mortality given the medical complexity of TS patients. Those who survive to dismissal have good survival. Later cardiovascular reoperations are not rare.

Temporal patterns of hospital readmissions according to disease category for patients after elective colorectal surgery.

The aim of this study was to identify temporal readmission patterns according to baseline disease categories to provide opportunities for targeted interventions. Retrospective analysis of consecutive adult (≥18 years) patients who underwent elective colorectal resections (2011-2017) at Mayo Clinic Rochester, MN. A prospective administrative database including patient demographics, procedure characteristics, discharge information and specifics on 30-day readmissions (to index facility) including timing and reasons was utilized. The ICD-9 codes were regrouped into the main pathologies Cancer, Crohn's disease (CD)/chronic ulcerative colitis (CUC), and diverticular disease. In total, 521 (7.2%) out of 7245 patients undergoing inpatient colorectal surgery were readmitted. In all increments of time from discharge (0-2 days: 31.3% of all readmissions, 3-7 days: 32.4% of all readmissions, 8-14 days: 18% of all readmissions, and 15-30 days: 18.3% of all readmissions), reasons for readmission differed significantly (all P < 0.001). Across all disease categories, early readmissions (within 2 days of discharge) were most likely due to ileus/obstruction (53.4% of early readmissions), whereas with 42.5%, infection was the most common cause for late readmissions (>7 days). Patients with home discharge were more likely to be readmitted earlier within the 30-day observation period (P = 0.099), whereas patients with a longer length of index hospital stay (>7 days) were readmitted later (P = 0.080). Reasons for readmission appear to be universal across different disease categories. Targeted educational and collaborative measures may help to mitigate the burden of hospital readmissions to index facilities.

Retrospective 15-Year Review of Anal Cytology Screening in Women at Mayo Clinic Rochester, Minnesota.

Anal cytology is a modality for anal cancer screening in high-risk women. In this retrospective study, we review risk factors associated with abnormal anal cytology and unsatisfactory anal cytology rates, and correlate findings of cytology with histological results. A retrospective cohort study of anal cytology screening in women at Mayo Clinic in Rochester, Minnesota from 2002 to 2018 was conducted. Three hundred fifty-seven women had a total of 592 anal cytologies performed. Three hundred seventeen women had screening anal cytology, whereas 40 women had anal cytology for surveillance given a history of anal intraepithelial neoplasia (AIN) or anal cancer. An unsatisfactory anal cytology result was found in 14.7%. Risk factors, type of follow-up, and correlation with histologic specimens were also reviewed. Histologic finding of AIN 2/3 correlated with abnormal anal cytology 84% of the time in this cohort. High-risk women should be screened on a periodic basis for anal cancer. Anal cytology is one possible modality that can be used. Further insight into AIN progression, regression, recurrence, and outcome after treatment will help direct future screening recommendations.

Clostridioides difficile Whole-genome Sequencing Differentiates Relapse With the Same Strain From Reinfection With a New Strain.

Current approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined. We recruited 468 subjects with CDI at Mayo Clinic Rochester between May and December 2016 and performed whole-genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of a recurrence of infection. The sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and the predicted ribotype. There were no correlations between C. difficile isolates based either on cgMLST or ribotype groupings and CDI outcome. An epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with ≤2 allelic differences, based on standard infection prevention and control assessment, revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting a relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having a reinfection based on the timing of recurrence, 3 had isolates with ≤2 allelic differences between them, suggesting a relapse, and 2 had isolates differing by >50 allelic differences, suggesting reinfection. Our findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on the timing of recurrence.

Abstract PD3-03: Impact of the breast cancer polygenic risk score on preventive endocrine therapy adherence and endocrine therapy usage on quality of life - The Genetic Risk Estimate (GENRE) trial

Abstract Background: Studies demonstrate breast cancer risk reduction of 50-65% with the use of endocrine therapy (ET) and yet drug uptake and adherence in this setting is suboptimal even among high risk women. A Polygenic Risk Score (PRS) comprised of 77 BC genetic susceptibility loci (Single Nucleotide Polymorphisms (SNP)) can provide a personalized risk assessment and potentially influence ET adherence. We assessed ET adherence at 1 year comparing women whose risk estimate increased due to PRS versus women whose risk estimate decreased due to PRS. The effect of ET use on quality of life (hot flashes, night sweats, vaginal dryness, weight gain, joint pain) was evaluated. Methods: Eligible women required either a 5 year Gail Model risk of ≥3% or 10 year IBIS ( International Breast Intervention Study or Tyrer-Cuzick model) of ≥5%. Women with a history of breast cancer (BC) or hereditary BC syndrome were excluded. High risk women were counseled at baseline using their Gail and IBIS risk scores and ET options were discussed including benefits and risks. Participants completed a self-reported questionnaire at baseline to assess their understanding of breast cancer risk and decision to take preventive ET. Blood samples were obtained and genotyped for 77 SNPs, and the odds ratio from the SNPs were used to modify the IBIS and Gail risk estimates. The BC -PRS risk estimate information was shared with study participants that reflected the IBIS and Gail risk estimates for 5 year, 10 year, &amp; lifetime BC risk with and without the PRS. Follow up questionnaires at year 1 were administered to assess drug adherence and ET usage on quality of life. Results: 151 women were enrolled at Mayo Clinic Rochester and CancerCare Manitoba from 2016 to 2017. The median age was 56.1 (range 36-76.4), 35.6% were premenopausal, 98.7% were Caucasian and 64.7% had&amp;gt;1 family member with BC. Median 5yr, 10yr, &amp; lifetime IBIS- PRS risk estimates were 3.8% (2.0-11.5), 7.9% (5.0-23.1), and 25.3% (5.5 to 92.2). At year 1 (n=112 women) 46 % of those with an increase in risk when considering the BC-PRS score and 16 % with a decrease in risk were taking ET ( p&amp;lt; 0.001). Types of ET taken: tamoxifen-18, raloxifene- 3, exemestane -14 and missing-1. Women taking ET reported weight gain ( 19.4% vs 6.7%, p=0.04) and more joint pain ( 27.8 % vs 12%, p=0.04) when compared to women not taking ET. Conclusion: In high risk women, BC-PRS risk estimates in addition to standard BC risk calculators had a significant impact on preventive ET adherence. ET use was associated with weight gain and joint pain. Citation Format: Sandhya Pruthi, Julian O Kim, Daniel Schaid, Andrew Cooke, Christina Kim, Benjamin Goldenberg, Jason Sinnwell, Debjani Grenier, Fergus Couch, Celine Vachon. Impact of the breast cancer polygenic risk score on preventive endocrine therapy adherence and endocrine therapy usage on quality of life - The Genetic Risk Estimate (GENRE) trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD3-03.

Pulmonary nodular and cystic light chain deposition disease: A retrospective review of 10 cases.

Light chain deposition disease (LCDD) rarely involves the lungs. We report clinical and radiologic findings of pulmonary LCDD. We retrospectively identified patients with biopsy-proven pulmonary LCDD seen at Mayo Clinic (Rochester, Minnesota) from January 1997 through December 2018. Demographic, clinical, and imaging features were analyzed. We identified 10 patients with pulmonary LCDD (median age at diagnosis, 55 years; range, 39-77 years). Eight patients were women and 7 were never-smokers. Dyspnea (n=3) and chest pain (n=3) were the most common respiratory symptoms. Associated conditions included Sjögren syndrome (n=6), sarcoidosis (n=1), and limited scleroderma (n=1). Eight patients had mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 9 patients with chest computed tomography (CT) images, 8 (89%) had cysts. Cysts were predominantly distributed in the lower lung and were round or oval. All patients had multiple cysts (5 patients had 1-5 cysts, 3 had >20 cysts). The median diameter of the largest cyst was 18mm (range, 5-68mm). All 9 patients had solid nodules (3 had >10 nodules). Five patients had subsolid nodules. The median diameter of the largest solid nodules was 13mm (range, 6-26mm). Positron emission tomography-CT images were available for 8 patients. The median maximum standardized uptake value of the most avid pulmonary nodule was 2.2 (range, 1.9-6.0). Two patients died during a median follow-up of 2.3 years (range, 0.5-9.9 years). Pulmonary LCDD is characterized by cysts and nodules. The disease is associated with MALT lymphoma, especially in the setting of Sjögren syndrome.

Onset, duration, and clinical impact of immune-related adverse events in Hodgkin lymphoma.

95 Background: The incidence of immune-related adverse events (irAEs) in patients (pts) with Hodgkin lymphoma (HL) treated with PD-1 antibodies (ICI) is reported at 28 - 36%. However, clinically relevant information on irAE onset, duration, or impact on ability to continue therapy in HL is lacking. Additionally, these incidence rates reflect CTCAE definition and grading, and not ASCO Clinical Practice Guidelines irAE-specific criteria (Brahmer et al, JCO 2018). The objectives of this study were to evaluate the rate and severity of irAEs in HL pts using ASCO criteria, to characterize irAE time profile and to assess their impact on continued therapy. Methods: HL pts who received a PD-1 inhibitor for the treatment of HL at Mayo Clinic Rochester between January 1, 2011 and March 1, 2018 were identified. We conducted a detailed, longitudinal retrospective chart review with definition and grading of irAEs in accordance with ASCO guidelines. Results: Fifty-one pts were identified (35% women, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 30 months (range: 1-70). Thirty-one pts (61%) had any irAE. Most common irAEs were inflammatory/bullous dermatoses (23.5%/5.9% any grade/grade3-4; median onset/duration of 81/57 days[d]), followed by thyroiditis (22%/0%; 86/84 d), colitis (14%/8%; 82/106 d), pneumonitis (14%/10%; 241/182 d), and hepatitis (14%/4%; 71/35 d). Fifteen pts (29%) required treatment with steroids. Among the total cohort, ICI was held for an irAE 28 times (50% of 56 total irAEs). Median treatment cycles held was 2.5 and ICI was permanently discontinued due to irAE in 18%. The most common irAE leading to treatment discontinuation was pneumonitis, followed by neuritis (5.9%/3.9%; 179/374 d), colitis, and rash. Conclusions: The rate of irAEs of 61% in this cohort as defined by ASCO consensus criteria was higher than reported in trials. Most irAEs were characterized by delayed onset of several months and prolonged duration, particularly pneumonitis and neuritis. Treatment discontinuation due to irAEs was infrequent overall. Further studies are needed to determine whether the development or duration of irAEs is predictive of treatment outcomes in HL.

Multimodality management of brain metastasis from colorectal cancer.

204 Background: More than 50% of colorectal cancer (CRC) patients will develop metastatic disease. Brain metastasis (BM) from colorectal cancer is uncommon (0.6-1.36%). This study aims to investigate the patient characteristics, treatment modalities and prognostic factors in this rare population. Methods: 104 patients with brain metastasis disease from CRC were identified from over 30,000 colorectal cancer patients at the Mayo Clinic Rochester between 1/1994 and 6/2019. A retrospective review was conducted by using data from electronic medical records (EMR). Statistical analysis utilized the Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: Among the 104 patients, 62 were male (59.6%) and 42 were female (40.4%). Median age at CRC diagnosis was 58.4 and at BM diagnosis was 61. Thirty-three patients had right-sided colon cancers, 27 patients had left-sided colon cancers and 39 patients had rectal cancer. Median time from CRC diagnosis to BM was 30.7 months. The majority of patients (58.7%) presented with a solitary brain lesion. Eighty-six patients (82.7%) had extracranial metastatic disease at BM diagnosis. Median survival was 7.0 months (95% CI 2.6-16.9) from BM diagnosis. Age &lt;70, solitary BM, surgery, radiation, and chemotherapy were associated with statistically significant improved survival on univariate and multivariate analysis. Multi-modality treatment including surgical brain lesion resection, postoperative stereotactic radiation (SRS) with/without whole brain radiation (WBRT), and chemotherapy significantly improved median overall survival (Table). Conclusions: Although BM from CRC carries poor prognosis, multi-modality treatment (surgery, radiation and systemic chemotherapy) for patients with limited BM improves clinical outcome. [Table: see text]

History and evolution of regional anesthesiology and acute pain medicine fellowship training

IntroductionIn 2016, individual training programs in regional anesthesiology and acute pain medicine (RA/APM) became eligible for accreditation by the Accreditation Council for Graduate Medical Education (ACGME), thereby culminating a process...

Spotlight in Plastic Surgery: April 2020

Spotlight in Plastic Surgery: April 2020

Increased Plasma Cells and Decreased B-cells in Tumor Infiltrating Lymphocytes are Associated with Worse Survival in Lung Adenocarcinomas.

Clinical significance of tumor-infiltrating plasma cells and B-cells in lung adenocarcinoma is not well known. CD3, CD20 and MUM1 immunostains were performed on representative tumor blocks selected from 120 consecutive lung adenocarcinoma cases treated by surgical resection at Mayo Clinic Rochester. CD3+ T-cells, CD20+ B-cells, and MUM1+ plasma cells were enumerated separately in the intraepithelial (IE) compartment and the stroma (ST) by digital image analyses using whole sections. Measured tumor-infiltrating plasma cells and B-cells were correlated with patient's overall survival (OS) using Cox proportional hazards analysis. Median age of patients was 69 years (range, 46-91 years) and 52 were male. Median numbers (interquartile range) of CD20+ B-cells per 1mm2 of tumor area (IE plus ST) and IE compartment within tumor area were 590 (224-1276) and 101 (38-109), respectively; the corresponding numbers of MUM1+ plasma cells were 298 (180-605), and 67 (22-145), respectively. The proportion of MUM1+ plasma cell among all TILs (MUM1+ cells/[CD3+ cells +CD20+ cells+MUM1+ cells] × 100) ranged 1%-59% (median13%) in the tumor area and showed a significant association with OS by univariate Cox analysis (negative correlation with hazard ratio (HR)=12.50 [95% confidence interval (CI), 1.75-89.27]). There was a significant association between IE CD20+ B-cells and the patient's OS in univariate analysis (positive correlation with HR=0.81 [95% CI, 0.68-0.96]). Both parameters remained significant by multivariate analysis. High plasma cell % among TILs in the tumor area and low IE B-cell count were associated with worse prognosis in lung adenocarcinoma patients.

Predicting Quality of Clinical Performance From Cardiology Fellowship Applications.

Variables in cardiology fellowship applications have not been objectively analyzed against applicants' subsequent clinical performance. We investigated possible correlations in a retrospective cohort study of 65 cardiology fellows at the Mayo Clinic (Rochester, Minn) who began 2 years of clinical training from July 2007 through July 2013. Application variables included the strength of comparative statements in recommendation letters and the authors' academic ranks, membership status in the Alpha Omega Alpha Honor Medical Society, awards earned, volunteer activities, United States Medical Licensing Examination (USMLE) scores, advanced degrees, publications, and completion of a residency program ranked in the top 6 in the United States. The outcome was clinical performance as measured by a mean of faculty evaluation scores during clinical training. The overall mean evaluation score was 4.07 ± 0.18 (scale, 1-5). After multivariable analysis, evaluation scores were associated with Alpha Omega Alpha designation (β=0.13; 95% CI, 0.01-0.25; P=0.03), residency program reputation (β=0.13; 95% CI, 0.05-0.21; P=0.004), and strength of comparative statements in recommendation letters (β=0.08; 95% CI, 0.01-0.15; P=0.02), particularly in letters from residency program directors (β=0.05; 95% CI, 0.01-0.08; P=0.009). Objective factors to consider in the cardiology fellowship application include Alpha Omega Alpha membership, residency program reputation, and comparative statements from residency program directors.

Erosive Esophagitis Portends a Benign Clinical Course in the Majority of Patients

Indefinite proton pump inhibitor (PPI) therapy and endoscopic evaluation for Barrett's esophagus is recommended for erosive esophagitis (EE). However, the clinical course of EE remains undefined. Adults with EE on esophagogastroduodenoscopy (EGD) were identified at Mayo Clinic Rochester between January 2003 and September 2005. Patients with repeat EGD performed after index endoscopy were included. Patients with a history of upper gastrointestinal surgery, esophageal cancer, achalasia, or Barrett's on initial EGD were excluded. Of 219 patients identified, 98 had LA grade A, 72 LA grade B, and 49 LA grade C esophagitis. Persistent EE was found in 27% on repeat endoscopy. No patients progressed to more severe grades of esophagitis. While discontinuation of PPI was associated with persistent esophagitis, long-term healing of esophagitis occurred in the majority of patients despite discontinuation of PPI. Grade A or B esophagitis and the absence of hiatal hernia were also independent predictors of esophagitis healing on multivariate analysis. The rate of Barrett's esophagus was similar among patients with LA grade A/B and C esophagitis on initial EGD (5% vs. 14%, p = 0.6). The majority of patients with EE demonstrated healing at follow-up endoscopy regardless of continued PPI use. A small proportion developed Barrett's esophagus, including those with LA grade A and B esophagitis, highlighting a potential role for repeat endoscopy in all grades of EE. A more conservative long-term PPI strategy may be reasonable in patients with LA grade A or B esophagitis in the absence of hiatal hernia.