Research Patient Data Registry Research Articles

IgG testing, immunoglobulin replacement therapy, and infection outcomes in patients with CLL or NHL: real-world evidence

AbstractPatients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) can develop hypogammaglobulinemia, a form of secondary immune deficiency (SID), from the disease and treatments. Patients with hypogammaglobulinemia with recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). This study evaluated patterns of immunoglobulin G (IgG) testing and the effectiveness of IgRT in real-world patients with CLL or NHL. A retrospective, longitudinal study was conducted among adult patients diagnosed with CLL or NHL. Clinical data from the Massachusetts General Brigham Research Patient Data Registry were used. IgG testing, infections, and antimicrobial use were compared before vs 3, 6, and 12 months after IgRT initiation. Generalized estimating equation logistic regression models were used to estimate odds ratios, 95% confidence intervals, and P values. The study population included 17 192 patients (CLL: n = 3960; median age, 68 years; NHL: n = 13 232; median age, 64 years). In the CLL and NHL cohorts, 67% and 51.2% had IgG testing, and 6.5% and 4.7% received IgRT, respectively. After IgRT initiation, the proportion of patients with hypogammaglobulinemia, the odds of infections or severe infections, and associated antimicrobial use, decreased significantly. Increased frequency of IgG testing was associated with a significantly lower likelihood of severe infection. In conclusion, in real-world patients with CLL or NHL, IgRT was associated with significant reductions in hypogammaglobulinemia, infections, severe infections, and associated antimicrobials. Optimizing IgG testing and IgRT are warranted for the comprehensive management of SID in patients with CLL or NHL.

Infection Outcomes and Hypogammaglobulinemia in Patients with Non-Hodgkin Lymphoma Treated with Immunoglobulin Replacement Therapy

CONCLUSIONS Patients diagnosed with non-Hodgkin lymphoma (NHL) histologies often develop hypogammaglobulinemia (HGG), a secondary immunodeficiency (SID) that is associated with exposure to NHL-related treatments. Those with HGG frequently experience infections, which represent the leading cause of death in NHL (33% of cases). Patients with HGG who experience recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). We aimed to assess real-world IgRT utilization and associated infection outcomes in patients with NHL. This retrospective, longitudinal, observational study evaluated HGG (immunoglobulin G [IgG] < 500 mg/dL) status and infection outcomes among adult patients diagnosed with NHL after 2010 who had ≥ 12 months of clinical data and ≥ 3 visits/year after NHL diagnosis and received immune globulin infusion (human), 10% (IG10% [ie, Gammagard Liquid]). De-identified clinical data from the Massachusetts General Brigham Research Patient Data Registry was used. IgG testing, infection outcomes, and antimicrobial use were compared 3 months before versus 3 months after initiation of IG10%. Generalized estimating-equation logistic regression models were used to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P values. A total of 13,232 patients with NHL were identified. Among patients with NHL, 623 (4.7%) received ≥ 1 IgRT during the follow-up period, of whom, 563 (90.4%) received IG10%. The majority of patients with NHL treated with IG10% were male (61.3%), White (90.1%), with a median (interquartile range [IQR]) age of 62 (53-69) years, and median (IQR) follow-up of 4.8 (2.3-7.7) years. Median (IQR) administrations of IG10% across recipients were 2 (1-4) and over half of patients (55.6%) received ≥ 2 IG10% administrations. Median (IQR) time from initiation of IG10% to end of follow-up was 25.6 (6.8-55.2) months. Most patients had ≥ 1 IgG test in the follow-up period (n = 532 [94.5%]), median (IQR) number of IgG tests was 10 (4-27), and 84.2% of patients had ≥1 IgG test result available before initiation of IG10%. Of the patients treated with IG10% who had IgG test results available (n = 532), 81.6% were identified with HGG (< 500 mg/dL). Few patients had IgG testing at the time of first NHL diagnosis (13.3%), and median (IQR) time from diagnosis to first IgG test was 4.9 (0.8-17.4) months. Of the patients with ≥ 2 IG10% administrations (n = 313), median (IQR) time from the first administration of IG10% to subsequent IgG testing was 1.0 (0.3-2.8) month. Most patients (91.3%) who received ≥ 2 IG10% administrations and ≥ 1 IgG testing had an IgG test between first and second administrations of IG10%. Median (IQR) serum IgG levels were higher in the 3 months following initiation of IG10% versus 3 months before initiation of IG10% (520.0 mg/dL [413.0-670.0] vs 339.0 mg/dL [228.0-405.0]), and significantly fewer patients had HGG (34.7% vs 83.0%, P < 0.0001). In addition, significantly lower odds of infection (OR 0.60, 95% CI 0.47-0.75), severe infection (OR 0.40, 95% CI 0.32-0.50), and associated antimicrobial use were observed 3 months after IG10% initiation (Figures 1 and 2). In this real-world study of patients with NHL, treatment with IG10% was shown to be associated with significantly lower rates of HGG as well as lower odds of infection, severe infection, and antimicrobial use 3 months after IG10% initiation. Guidelines and consensus-based recommendations are needed to optimize the use of IgG testing, initiation of IgRT, and SID management in patients with NHL.

1895. Omadacycline for the Treatment of Non-Pulmonary Mycobacterial Infections: a Single-Center Retrospective Review

Abstract Background Infections due to rapidly growing mycobacteria (RGM) such as M. abscessus, M. chelonae and M. fortuitum typically require long and toxic regimens, with complex resistance patterns and limited oral options further producing suboptimal efficacy. Since its approval in 2018, however, the tetracycline derivative omadacycline has established new options in antibiotic management. We report here clinical experience with the use of omadacycline for non-pulmonary RGM infections within the Mass General Brigham (MGB) system. Methods The study was approved by the MGB Institutional Review Board (2022P001578). Electronic ambulatory notes in the MGB Research Patient Data Registry (RPDR) from 2012-present were filtered by the term “omadacycline,” and manual chart review was conducted for individuals treated for non-pulmonary RGM infections. Flow diagram of chart review procedure for identification of non-pulmonary RGM patients Results Chart review revealed 25 patients with omadacycline-treated non-pulmonary RGM infections. The median age was 50, 52% female and 48% male. In total, 16 were infected with M. abscessus (64%), 8 with M. chelonae (32%), and 1 with M. immunogenum. 18 cases were skin and soft tissue infections (72%), 4 cases were bone and joint infections (16%), and 3 cases were disseminated infections (12%). Most patients (88%) received omadacycline as part of a step-down or a salvage regimen; 3 (12%) received omadacycline in initial treatment. 17 patients (68%) had completed regimens as of April 2023. Among these cases, the median duration of omadacycline use was 5 months (range=0.25-16). Patients within this cohort generally experienced clinical improvement. Adverse effects–most commonly nausea–were noted in 6 (24%) cases. No patients were discontinued due to the severity of these effects, though one regimen was temporarily paused due to hyperlipasemia. Non-pulmonary RGM patient cohort demographics, Mycobacterial species, and site of infection. Conclusion Omadacycline is an increasingly common component of the treatment of RGM infections, with use in multidrug regimens appearing generally effective and well-tolerated. Limitations of this study include its retrospective nature and evaluation within a single health system. To our knowledge, however, this is the largest series on omadacycline in RGM infections reported to-date. This analysis provides support for the further evaluation of omadacycline outcomes among patients with RGM infections. Disclosures All Authors: No reported disclosures

Abstract 18454: Temporal Trends in Assessment and Management of Iron Status in Patients With Heart Failure: A Multi-Institutional Study

Background: Over the last decade there has been extensive investigation of iron deficiency in heart failure (HF). HFrEF patients are often refractory to oral iron supplementation whereas intravenous (IV) iron repletion has been shown to improve functional capacity, prompting a Class II guideline recommendation to assess iron stores and replete iron intravenously. The purpose of this study is to understand temporal patterns in assessment of iron status as well as utilization of oral and IV iron preparations in patients with HF. Methods: The Mass General Brigham (MGB) Research Patient Data Registry (RPDR) was used to conduct a retrospective analysis of patients with both HFrEF and HFpEF across 3 1-year intervals in 2012, 2017, and 2022. Circulating levels of iron, ferritin, and transferrin saturation (TSAT) were assessed. Patients were further classified according to the HF guideline-based definition of iron deficiency (ferritin <100 ng/mL or 100-299 ng/mL with a TSAT < 20%). Iron deficient (ID) HF patients were assessed for use and frequency of IV iron or oral iron for repletion. Results: Electronic health records within the MGB Healthcare System identified 23,687 total HF patients in 2012, 25,271 in 2017, and 36,059 in 2022. Among these patients, the percentage with iron studies measured within the calendar year were 48%, 62%, and 90% respectively. Of those with HF 5,557 (23%), 8,460 (33%), and 19,955 (55%) met guideline-based diagnostic criteria for iron deficiency. Oral iron supplements were used in 68%, 44%, and 19% of all ID HF patients. IV iron was given to only 4%, 11%, and 14% of ID patients ( Figure ). Conclusion: The temporal trends of iron assessment and repletion demonstrate a significant increase in assessment of iron stores by health care providers but persistent utilization of oral formulations in excess of IV formulations to treat ID. These data suggest a significant gap in implementation of a therapy associated with functional improvement in HF.

Infection Outcomes and Hypogammaglobulinemia in Patients with Chronic Lymphocytic Leukemia Treated with Immunoglobulin Replacement Therapy

CONCLUSIONS Hypogammaglobulinemia (HGG), a secondary immunodeficiency (SID), can manifest in patients with chronic lymphocytic leukemia (CLL) due to the disease and its treatments. Up to half of all deaths from CLL are attributed to infection; however, use of immunoglobulin replacement therapy (IgRT) for the prevention of infections in selected patients varies. We aimed to assess real-world IgRT utilization and infection outcomes in patients with CLL. A retrospective, longitudinal study evaluating real-world IgRT use in adult patients with CLL diagnosed after 2010, with ≥ 3 visits/year and ≥ 12 months of clinical data, was conducted. De-identified clinical data came from the Massachusetts General Brigham Research Patient Data Registry. Immunoglobulin G (IgG) testing, infection outcomes, and antimicrobial use were compared before versus after IgRT initiation. Generalized estimating equation logistic regression models calculated odds ratios (ORs), 95% CIs, and P-values. Of 3960 patients with CLL assessed, 2652 (67.0%) patients had IgG testing (29.0% tested at CLL diagnosis); 917 (34.6%) had HGG (IgG level < 500mg/dL). Median (interquartile range [IQR]) age was 68.0 (60.0, 76.0) years, 61.2% were men, 67.8% were treatment-naïve, and median (IQR) follow-up duration was 4.8 (2.4, 7.4) years. Among recipients of IgRT (n = 259), 56.8% received ≥ 2 administrations and the median (IQR) number of IgRT administrations was 2.0 (1.0, 4.0). Median (IQR) time from CLL diagnosis to IgRT initiation was 38.0 (11.4, 64.7) months. Significantly fewer patients had HGG 3 months after IgRT versus 3 months before (33.8% vs 72.8%; P < 0.0001). Significantly lower odds of infections and antimicrobial use were observed after IgRT initiation in 3- and 6-month time periods for: all infections, sinopulmonary and skin or soft tissue infections, infections requiring antimicrobials, all severe infections, severe sinopulmonary and skin or soft tissue infections, and severe infections requiring antimicrobials ( Table). In this real-world study of patients with CLL, IgRT was associated with significant reductions in HGG, infection rates, and infections requiring antimicrobials. Guidelines are needed to optimize IgG testing, IgRT initiation, and SID management for patients with CLL.

THU266 Lowered HbA1c In Individuals With Long-term Type 1 Diabetes Undergoing BCG Bladder Cancer Therapy

Abstract Disclosure: H. Dias: None. W. Kühtreiber: None. D.L. Faustman: None. Originally developed for the prevention of tuberculosis, the bacillus Calmette-Guérin (BCG) vaccine has shown benefit in diverse human diseases, including infection resistance, allergies, multiple sclerosis and autoimmune diabetes. BCG has also been approved in the United States and Europe since 1972 for early-stage bladder cancer, where it is administered commonly as 6 doses via intravesical therapy for 6 weeks (“high-dose intravesical BCG”). We analyzed three large databases-the Management Science Associates database (with Quest Diagnostics data) (N=263 million adults), the Research Patient Data Registry (RPDR) from the Massachusetts General Brigham (MGB) system (N=6.5 million), and data from Optum Labs (OL)(N=45 million) -for a correlation between high-dose intravesical BCG and HbA1c levels in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D). We identified subjects with documented T1D (N=19) or T2D (N=106) undergoing BCG therapy for bladder cancer, and then retrospectively assessed BCG’s subsequent year-by-year impact on blood sugar trends. T1D records were identified by searching for T1D diagnosis and insulin usage; records showing any history of oral hypoglycemic agents (e.g., metformin) were excluded. T2D records were searched for using T2D diagnosis and exclusion of any T1D diagnosis. No patients had a history of BCG treatment/vaccination other than for bladder cancer. Patients with T1D in the datasets showed downward trends in HbA1c values after high-dose intravesical BCG, but not patients with T2D. The data suggests that high-dose intravesical BCG therapy may contribute towards a drop in HbA1c values in T1D, but not T2D. This is consistent with earlier interventional trials of the BCG vaccine in longstanding T1D. Presentation: Thursday, June 15, 2023

Clinical outcomes associated with type II myocardial infarction caused by bleeding

T2MI is caused by a mismatch between myocardial oxygen supply and demand. One subset of individuals is T2MI caused by acute hemorrhage. Traditional MI treatments including antiplatelets, anticoagulants, and revascularization can worsen bleeding. In this study, we aim to describe and report clinical outcomes of clinically-adjudicated T2MI patients due to bleeding, stratified by treatment approach. The Mass General Brigham Research Patient Data Registry followed by manual physician adjudication was used to identify individuals with T2MI caused by bleeding between 2009 and 2022. We defined 3 treatment groups: (1) an invasively managed group, (2) a pharmacologic group who received antiplatelet and anticoagulant therapy but no procedures, and (3) a conservatively managed group who received no procedures or anticoagulant/antiplatelet therapy. Baseline characteristics, diagnostic testing, treatment regimens, and clinical outcomes for 30-day, mortality, re-bleeding, and readmission were abstracted and outcomes were compared between treatment groups with chi-squared tests. We identified 5712 individuals coded as having acute bleeding, of which 1017 (17.8%) were coded as having T2MI during their admission. After manual physician adjudication, 73 individuals (7.2%) met the criteria for T2MI caused by bleeding. Among the individuals with T2MI caused by bleeding, 18 were managed invasively, 39 received pharmacologic therapy alone, and 16 were managed conservatively. The invasively managed group experienced lower mortality rates (5.6% vs 37.5%, p = 0.021) yet higher readmission rates (22.2% vs 0%, p = 0.045) than the conservatively managed group. The pharmacologic group experienced lower mortality rates (10.3% vs 37.5%, p= 0.017) yet higher readmission rates (35.9% vs 0%, p = 0.005) than the conservatively managed group. Finally, there were no differences in terms of re-bleeding episodes between the 3 different groups. Individuals with T2MI associated with acute hemorrhage are a high-risk population. Those patients treated with standard procedures experienced higher readmission but lower mortality rates than patients with conservative management. Although these results are not risk-adjusted and likely reflect treatment-selection bias, they at least raise the possibility of testing ischemia-reduction approaches for such high-risk populations. Future clinical trials are required to validate any treatment strategies for T2MI caused by bleeding.

Patterns of IgG Testing and Rates of Hypogammaglobulinemia in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

BackgroundInfections cause substantial morbidity and up to 50% of deaths in patients with chronic lymphocytic leukemia (CLL). Hypogammaglobulinemia (HGG), a reversible risk factor for severe infections, is associated with CLL and its therapies. We evaluated patterns of immunoglobulin G (IgG) testing and immunoglobulin replacement therapy (IgRT) initiation in patients with CLL. MethodsThis retrospective, longitudinal study evaluated the real-world use of IgG testing in adults with CLL diagnosed after 2010 using deidentified clinical data from the Massachusetts General Brigham Research Patient Data Registry. Eligible patients had ≥12 months of clinical information post-CLL diagnosis and ≥3 visits/year. Timing of IgG testing, IgRT initiation, and serum IgG levels before and after IgRT initiation were examined. Results were reported with descriptive statistics including medians and interquartile range (IQR); P-values were calculated using McNemar’s test. ResultsThe cohort included 2842 patients; median (IQR) age was 69 (60, 76) years, 61.3% were men, 92.9% were White, 75.2% were treatment-naïve, and median (IQR) follow-up was 4.2 (2.2, 6.8) years. Of 1352 (47.6%) patients with IgG testing during the follow-up period, median (IQR) number of IgG tests was 0.5 (0.2,1.2) per patient/year; 34.1% had HGG (IgG < 500 mg/dL). Median (IQR) time from CLL diagnosis to first IgG test was 6.9 (0.9, 22.6) months. Number of IgG tests, IgRT administrations, timing of IgRT initiation from diagnosis and IgG testing, and serum IgG levels before and after IgRT initiation are described in the Table. Among patients with ≥1 IgRT administration, median (IQR) IgG serum levels improved and the proportion of patients with HGG decreased ≥12 months following IgRT initiation (Table). ConclusionsAs CLL treatment evolves, it is important to identify which patients are at greatest risk of infections and to standardize HGG screening. This study demonstrates that IgG levels are not assessed frequently post-CLL diagnosis, nor uniformly reassessed following initiation of IgRT. Among patients with CLL receiving IgRT, IgG levels improved after IgRT initiation. Thus, increased awareness and IgG screening might reduce severe or recurrent infections in the CLL patient population.Takeda Pharmaceuticals USA, Inc. funded the study and writing support.

Predictors of Conversion from Positive to Negative Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Status (P9-3.011)

<h3>Objective:</h3> The goal of this study is to characterize the clinical course of patients with Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD) who seroconvert from a positive to negative MOG antibody status, and to determine predictors of seroconversion. <h3>Background:</h3> MOGAD is a neuroinflammatory disorder characterized by demyelination of the optic nerve, brain, or spinal cord, and can be either relapsing or monophasic. Persistent MOG antibody positivity has been identified as a potential predictor of disease-related relapses, however there has been limited research regarding what determines whether patients remain seropositive or convert to a negative MOG antibody status. <h3>Design/Methods:</h3> The Massachusetts General Hospital Neuroimmunology Clinic maintains a list of patients with MOGAD based on queries of the Massachusetts General Brigham Research Patient Data Registry database and updated with clinic visits. Patients evaluated through July 2022 were included in a chart review focused on MOG serostatus, titer levels, and potential predictors of MOG serostatus. Data analysis was conducted in Stata/SE 17.0. <h3>Results:</h3> We identified 66 patients who had at least 2 MOG antibody tests 6 months apart (60.6% females and 39.4% males). Of these, 47 had persistently positive MOG titers, and 18 had positive titers that became negative. 5 individuals had negative titers that later converted to positive. Of the 18 patients that developed negative titers, only 1 had a subsequent documented relapse, which was associated with discontinued immunotherapy and titers which became positive again at the time of relapse. Predictors of conversion to negative IgG on multivariate logistic regression included low initial MOG titers (defined as titers &lt;1:100), male sex, and childhood onset of disease. <h3>Conclusions:</h3> Low initial MOG titers, male sex, and childhood onset of disease can help predict future conversion to negative MOG serostatus. Further analysis of this cohort will focus on the effect of various immunotherapies and their timing on MOG antibody status. <b>Disclosure:</b> Ms. Hayman has nothing to disclose. The institution of Dr. Vishnevetsky has received research support from National MS Society. The institution of Dr. Vishnevetsky has received research support from NIH (NeuroNext). Ms. Romanow has received research support from Freeman Pain Award @ Harvard Medical School. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mitsubishi Pharma. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB Pharma. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Levy has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Levy has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Levy has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Various law firms. The institution of Dr. Levy has received research support from National Institutes Health.

MP72-19 DECREASED UTILIZATION OF LOW-VALUE HEALTH CARE SERVICES DURING THE COVID-19 PANDEMIC

You have accessJournal of UrologyCME1 Apr 2023MP72-19 DECREASED UTILIZATION OF LOW-VALUE HEALTH CARE SERVICES DURING THE COVID-19 PANDEMIC Tracy X. Han, Nguyen David-Dan, Zhiyu (Jason) Qian, Benjamin V. Stone, Peter Herzog, Stuart R. Lipsitz, Alexander P. Cole, Toni K. Choueiri, and Quoc-Dien Trinh Tracy X. HanTracy X. Han More articles by this author , Nguyen David-DanNguyen David-Dan More articles by this author , Zhiyu (Jason) QianZhiyu (Jason) Qian More articles by this author , Benjamin V. StoneBenjamin V. Stone More articles by this author , Peter HerzogPeter Herzog More articles by this author , Stuart R. LipsitzStuart R. Lipsitz More articles by this author , Alexander P. ColeAlexander P. Cole More articles by this author , Toni K. ChoueiriToni K. Choueiri More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003340.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low value health care is defined as care in which the potential to cause harm is greater than benefit. We hypothesize that rationing of health care services during the pandemic decreased the delivery of low value services. METHODS: Data was retrieved from the Mass General Brigham Research Patient Data Registry. High value care services were defined by U.S. Preventive Services Task Force guidelines, while low value care services were adapted for claims as described in the literature. Twenty-one services (4 high value and 17 low value) had adequate volume for analysis. Three month periods were considered, consisting of the pandemic period (Q4: 3/2/20 to 6/1/20) and control periods preceding the pandemic (Q1: 12/1/18 to 3/1/19; Q2: 3/2/19 to 6/1/19; and Q3: 12/1/19 to 3/1/20). Ratio measures of services per period were used to account for seasonality and differences in frequency.The 2019 high value (H) care ratio (Y0H = NHQ2/NHQ1) illustrates relative service counts during a typical year and the 2020 ratio (Y1H = NHQ4/NHQ3) represents the change due to the pandemic. Difference in ratios YH=Y1H-Y0H less than zero reflects a reduction in high value services during the pandemic. The same calculation was made for low value (L) procedures; YL=Y1L-Y0L. The difference between YL and YH is the difference in differences (DID) estimator and illustrates the differential decline in services. YH- YL greater than zero suggests that low value care declined to a greater degree than high value care. Subdivision DID in ratio analyses were performed for cancer and non-cancer care. RESULTS: Included in this analysis were 3,271,957 patients. Mean age was 51.4 years, 59.1% of patients were female, and 71.7% were non-Hispanic. Of 21 identified services, 18 had a reduction in volume during the pandemic. The YL for PSA testing in men older than 75 was -0.81. The DID in ratios of all care was 0.08 (p<0.01), suggesting a modest decline in low-value care (Figure 1). The reduction was more pronounced for cancer care with a DID in ratios of 3.39 (p<0.01). CONCLUSIONS: We observed a reduction in both low and high value care with a greater reduction in low value services, especially for cancer care. Limitations include use of data from a single health system, limited number of services, and short time periods given the rapid onset of the pandemic. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1032 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tracy X. Han More articles by this author Nguyen David-Dan More articles by this author Zhiyu (Jason) Qian More articles by this author Benjamin V. Stone More articles by this author Peter Herzog More articles by this author Stuart R. Lipsitz More articles by this author Alexander P. Cole More articles by this author Toni K. Choueiri More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement PDF downloadLoading ...

Assessment of complete pathologic response after neoadjuvant immunotherapy for MSI-H gastrointestinal cancers.

43 Background: Immunotherapy (IO) has shown remarkable efficacy in gastrointestinal (GI) cancers with high microsatellite instability (MSI-H). We evaluated real world outcomes of patients treated with neoadjuvant IO for MSI-H colorectal (CRC) and gastroesophageal (GE) cancers. Methods: We queried diagnoses, pathology reports, and clinic notes of patients receiving IO at Massachusetts General Hospital from October 2014 to March 2022 using the Research Patient Data Registry and MATLAB. 1140 patients were identified with esophageal, gastric, colon, or rectal primaries. Of these, 56 were MSI-H and seven received neoadjuvant IO with curative intent. Results: Of the seven patients who received neoadjuvant IO for MSI-H CRC or GE cancers, three patients achieved complete pathologic response (pCR). Three patients had partial responses; one had a single residual lymph node tumor cell, one had residual T1b tumor and negative nodes, and one had residual T3 tumor and positive nodes. All patients with pCR had non-metastatic disease. Three of four patients with partial responses or progression had metastatic disease. Five patients had no recurrence by median follow-up of 10 months post-resection. One patient's cancer recurred 15 months post-resection, and one patient had progressive disease on neoadjuvant IO so did not undergo primary resection. Conclusions: Neoadjuvant IO shows promise for MSI-H GI cancers. Three of seven patients (43%) had pCR and three others (43%) had notable partial responses. There is a need to understand IO-refractory primary tumors and the differing effects of IO in local versus metastatic disease. While our data is limited by sample size, larger clinical trials can establish the safety and utility of neoadjuvant IO, potentially sparing many patients from surgery. We will collaborate with other centers for a larger scale analysis on neoadjuvant IO in MSI-H GI cancers. [Table: see text]

Patient-Reported and Clinical Outcomes Among Patients With Calciphylaxis

ObjectiveTo describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes. Patients and MethodsPatients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models. ResultsOur analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, −0.71; P=.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; P=.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; P=.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; P<.05) but did not predict lesion improvement or survival. ConclusionPain control remains a challenge among hospitalized patients with calciphylaxis. Surgical debridement and hyperbaric oxygen therapy may improve pain intensity. Pain improvement predicted a lower risk of future amputation.

Differential Effects of COVID-19 Hospitalization on the Trajectory of Liver Disease Progression.

Patients with chronic liver disease (CLD) were significantly affected by COVID-19. Despite evidence of acute hepatic injury and increased mortality, the long-term effects of COVID-19 hospitalization on the natural history of CLD patients are unknown. The Massachusetts General Hospital COVID-19 registry was used to obtain a cohort of CLD patients hospitalized between March 8 and June 3, 2020. The Partners Research Patient Data Registry was used to develop a matched CLD patient control list without COVID-19. Fibrosis-4 index (FIB-4), nonalcoholic fatty liver disease fibrosis score (NFS), and model for end-stage liver disease/Na (MELD-Na) scores were calculated pre-, day of, and 1-year post-discharge from admission. Unpaired t-test was used to compare continuous variables. Fifty-two COVID-19 patients and 92 control patients with CLD were included. Patients with non-cirrhotic CLD who were hospitalized for COVID-19 had an acute rise in FIB-4 on admission with subsequent improvement on one-year follow-up demonstrating no difference in progression of liver disease compared to the controls (P= .87, confidence interval [CI]-0.088 to 0.048). Similar trends were observed in nonalcoholic fatty liver disease patients using NFS (P= .48, CI-0.016 to 0.023). In contrast, patients with cirrhosis experienced rise in MELD-Na postadmission compared to the control cirrhosis group (0.35 vs-0.076/month; P= .04, CI-0.827 to-0.025), suggesting a potential for long-term consequences of COVID-19. Non-cirrhotic CLD patients who survive COVID-19 hospitalization do not appear to have change in FIB-4, NFS scores at one year. However, patients with cirrhosis exhibit increasing MELD-Na one-year post-COVID suggesting a differential effect of acute COVID-19 on the trajectory of established cirrhosis.

Validation of claims-based algorithms to identify non-live birth outcomes.

Perinatal epidemiology studies using healthcare utilization databases are often restricted to live births, largely due to the lack of established algorithms to identify non-live births. The study objective was to develop and validate claims-based algorithms for the ascertainment of non-live births. Using the Mass General Brigham Research Patient Data Registry 2000-2014, we assembled a cohort of women enrolled in Medicaid with a non-live birth. Based on ≥1 inpatient or ≥2 outpatient diagnosis/procedure codes, we identified and randomly sampled 100 potential stillbirth, spontaneous abortion, and termination cases each. For the secondary definitions, we excluded cases with codes for other pregnancy outcomes within ±5 days of the outcome of interest and relaxed the definitions for spontaneous abortion and termination by allowing cases with one outpatient diagnosis only. Cases were adjudicated based on medical chart review. We estimated the positive predictive value (PPV) for each outcome. The PPV was 71.0% (95% CI, 61.1-79.6) for stillbirth; 79.0% (69.7-86.5) for spontaneous abortion, and 93.0% (86.1-97.1) for termination. When excluding cases with adjacent codes for other pregnancy outcomes and further relaxing the definition, the PPV increased to 80.6% (69.5-88.9) for stillbirth, 86.6% (80.5-91.3) for spontaneous abortion and 94.9% (91.1-97.4) for termination. The PPV for the composite outcome using the relaxed definition was 94.4% (92.3-96.1). Our findings suggest non-live birth outcomes can be identified in a valid manner in epidemiological studies based on healthcare utilization databases.

RF28 | PSUN185 The effects of diabetes and glycemic control on cancer outcomes in individuals with metastatic breast cancer

Abstract Background While a well-established relationship between diabetes and breast cancer exists, it remains unclear how diabetes impacts breast cancer outcomes. This study aims to determine the impact/association of diabetes and hyperglycemia on cancer progression and mortality in individuals with metastatic breast cancer. Methods Patients with metastatic breast cancer between 2010-2021 were identified using the metastatic breast cancer database at a single academic center. The Research Patient Data Registry, a data warehouse of all patients receiving care in the hospital network was then used to determine the diabetes status of each participant. A participant was categorized as having diabetes if they fulfilled pre-specified criteria (international classification of diseases (ICD) 9 or 10 code for diabetes, or a hemaglobin A1c ≥6.5%, or a random blood glucose (RBG) ≥200 mg/dL and documented use of glucose-lowering agents), while controls were defined as individuals who did not fulfill the previous criteria. We evaluated the effects of diabetes on 1) overall survival (OS) and 2) the interval from initiation of first-line metastatic therapy to initiation of a second-line regimen due to documented progression of disease (a surrogate measure of progression-free survival). The impact of glycemic control on OS and duration of first-line therapy was also assessed. Results We compared 244 patients with diabetes (median age 57.6 years) to 244 patients without diabetes, who were matched for age, gender, ethnicity and hormone-receptor (HR) status. OS at 5 years (diabetes: 54%, CI; 47-62% vs. controls: 56%, CI; 49-63%, p=0.65) and freedom from initiating a second-line regimen at 2 years (diabetes: 43%, CI; 36-50% vs. controls: 44%, CI; 36-51%, p=0.33) were not statistically different between groups. However, in an 8-year landmark subgroup analysis, OS was better amongst controls than those with diabetes (diabetes [n=27]: 67%, CI; 48-86% vs. Controls [n=28]: 87%, CI; 73-100%, p=0.047at 10 years). Poor glycemic control (median RBG &amp;gt;180 mg/dL or median HbA1c &amp;gt;7%) was not associated with increased mortality at 5 years but was associated with a trend towards worse freedom from initiating a second-line regimen at 2 years when compared to good glycemic control. In a sub-group analysis based on HR status, there were no differences in OS at 5 years, or freedom from initiating a second-line regimen at 2 years between the two glycemic groups (≤180 mg/dL vs &amp;gt;180 mg/dL on two or more occasions in a month) for any of the HR subgroups. Conclusions These data provide some reassurance that hyperglycemia may not be a major contributor to overall mortality in the first 5 years, in most individuals with metastatic breast cancer. However, amongst longer-term survivors, diabetes was associated with worse survival, suggesting that individualized diabetes and glycemic goals should, therefore, be considered in patients with metastatic breast cancer. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.

PMON153 Changes in size of pituitary microadenomas, a retrospective cohort study

Abstract Background The estimated prevalence of pituitary lesions is 22.5% in radiologic studies. The solid and/or cystic lesions are usually described as incidentaloma. Most pituitary incidentalomas are microadenomas (lesion size &amp;lt;1 cm). In 2011, The Endocrine Society published guideline on following incidental pituitary lesion. However, few studies evaluated the dynamic changes in pituitary incidentaloma. Method: In this retrospective cohort study, patients with pituitary microadenomas were identified from our institution database by the Research Patient Data Registry from 11/2003 to 3/2021. We performed chart review to collect data relevant to demographic and pituitary imaging findings. The study was approved by our institution IRB.The patients with the diagnosis of pituitary microadenoma (tumor size &amp;lt; 10 millimeter (mm)) were included in this study. To eliminate the medication effects on the tumor size, we excluded the patients with diagnosis of prolactinoma and patients on dopamine agonists or somatostatins. We performed linear regression test. We performed Kaplan-Meier survival curve analysis. Results Over 15 years, among total 177 subjects, 78 (44%) had unchanged size of the microadenoma, 49 (27%) had increase size, 34 (19%) had decrease in size, and 16 (9%) had both increased and decreased size. Ten (6%) subjects had transsphenoidal pituitary tumor resection. Among 128 female subjects, 53 (41%) had unchanged size, 35 (27%) had increased size, 28 (22%) had decreased size, and 12 (9%) had both increased and decreased size. Seven subjects (5%) had transsphenoidal pituitary tumor resection. Among 49 male subjects, 25 (51%) had unchanged size, 14 (27%) had increased size, 6 (12%) had decreased size, and 4 (8%) had both increased and decreased size. Three patients (6%) had tumor resection. Over the 15 years, the changes in the size of microadenomas are between -6 mm to 6 mm. There were 6 (3%) subjects with tumor size increase into macroadenoma category. The slope by linear analysis was 0.85 (95% CI: -0.28 to 1.99) in percentage change. The slope was 0.02 (95% CI: -0.012 to 0.054) in tumor size change in mm. The slope was not significantly deviated from zero by percentage change (p = 0.14) or size change in mm (p = 0.21). The median time of microadenomas remained unchanged were 6.5, 7.7, and 6.5 years in total, male and female respectively. There was no significant difference in size change among total, male and female (p = 0.947). Conclusion Our study has shown that majority of pituitary microadenomas remain unchanged or decreased in the size over 15 years. The maximal size increase was 6 mm. There were no significant changes in tumor size over the study period. Our study suggests that less frequent surveillance pituitary MRI in incidental pituitary microadenomas is safe. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

144 Clinical epidemiology of Masson tumor

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson tumor–a rare, benign vascular lesion typically presenting in the skin as a subcutaneous nodule – may be clinically mistaken for other neoplasms such as hemangiomas and lipomas. IPEH is classically categorized into three types:1) pure type arising in dilated endovascular spaces; 2) mixed type developing from preexisting vascular abnormalities; 3) extravascular type. While the prognosis of IPEH is excellent, it must be differentiated from malignant tumors such as angiosarcomas, which may require intensive treatments. Because the literature on IPEH is limited, we sought to characterize clinical and pathological features of IPEH. Subjects were identified using the Mass General Brigham (MGB) Research Patient Data Registry and included individuals with pathologically proven diagnosis of IPEH from 1/1980 to 8/2021 at Massachusetts General Hospital, Brigham and Women’s Hospital (BWH), and the BWH Faulkner Hospital. Demographic information, clinical documentation, and pathology reports were reviewed for data extraction. 261 individuals were diagnosed with IPEH, with the majority being women (60%) and white (74%). The average age at diagnosis was 53 years old [4-98 years old]. The most frequently involved anatomic sites were the upper (29%) and lower (24%) extremities. Common initial clinical diagnoses of lesions were cysts, hemangiomas, and lipomas. The pure subtype of IPEH was the most common (50%), followed by the mixed (46%) and extravascular subtypes (4%). Extravascular IPEH occurred more frequently in women (5%) compared to men (1%). We found that most clinicians’ initial impressions prior to biopsy did not include the final diagnosis of IPEH -- often using vague terms such as “soft tissue mass” -- indicating a potential need for greater awareness of this condition. Given the differential diagnosis of IPEH often includes conditions such as melanoma or angiosarcoma, clinicopathologic correlation is of utmost importance for this uncommon vascular lesion.

220 Clinical epidemiology of ecthyma gangrenosum

Ecthyma gangrenosum (EG) is an uncommon infectious cutaneous eruption. It typically presents with painless macules, transitions to hemorrhagic vesicles, and eventually evolves into necrotic ulcers. EG should be recognized early and treated aggressively as it is associated with significant morbidity. Because the literature on this disease is limited, we sought to characterize clinical and pathologic features of EG in a large, multi-institution academic center. Patients were identified using the Mass General Brigham Research Patient Data Registry and included individuals with a diagnosis of EG from 1/1980 to 9/2021 seen at Massachusetts General Hospital, Brigham and Women’s Hospital (BWH), and the BWH Faulkner Hospital.

Positive Predictive Value of MOG-IgG for Clinically Defined MOG-AD Within a Real-World Cohort.

Myelin oligodendrocyte glycoprotein antibody associated disease (MOG-AD) is a CNS demyelinating disease, typically presenting with optic neuritis, transverse myelitis, and/or ADEM-like syndromes. The positive predictive value (PPV) of MOG-IgG testing by live cell-based assay was reported to be 72% in a study performed at the Mayo Clinic using a cut-off of 1:20. PPV may vary depending upon the tested population, thus supporting further investigation of MOG-IgG testing at other centers. In this real-world institutional cohort study, we determined the PPV of serum MOG-IgG for clinically defined MOG-AD in our patient population. The Massachusetts General Brigham Research Patient Data Registry database was queried for patients with positive serum MOG-IgG detection, at least once, between January 1, 2017 and March 25, 2021. All were tested via the MOG-IgG1 fluorescence-activated cell sorting assay (Mayo Laboratories, Rochester, MN). MOG-IgG positive cases were reviewed for fulfillment of typical MOG-AD clinical features, determined by treating neurologists and study authors. Of 1,877 patients tested, 78 (4.2%) patients tested positive for MOG-IgG with titer ≥1:20, and of these, 67 had validated MOG-AD yielding a PPV of 85.9%. Using a ≥1:40 titer cutoff, 65 (3.5%) tested positive and PPV was 93.8%. Three MOG positive cases had a prototypical multiple sclerosis diagnosis (RRMS n = 2, titers 1:20 and 1:40; PPMS n = 1; 1:100). The treating diagnosis for one RRMS patient with a 1:40 titer was subsequently modified to MOG-AD by treating neurologists. Validated diagnoses of the remaining positive patients without MOG-AD included: migraine (n = 2, titers 1:20, 1:100), inclusion body myositis (n = 1, titer 1:100), autoimmune encephalitis (n = 2, titers 1:20, 1:20), hypoxic ischemic brain injury (n = 1, titer 1:20), IgG4-related disease (n = 1, titer 1:20), and idiopathic hypertrophic pachymeningitis (n = 1, titer 1:20). In our cohort, the PPV for MOG-IgG improved utilizing a titer cut-off of ≥1:40. The presence of positive cases with and without demyelinating features, emphasizes a need for testing in the appropriate clinical context, analysis of titer value and clinical interpretation.

Impact of anticoagulation/antiplatelet therapy on femoropopliteal bypass graft outcomes

BackgroundAnticoagulant and antiplatelet (AC/AP) medications have been reported to improve bypass graft patency, however, the optimal AC/AP strategy remains unclear in the heterogenous peripheral artery disease population. MethodsA multi-institutional retrospective review utilizing the Research Patient Data Registry database from 1995 to 2020 was performed for all patients who underwent femoropopliteal bypass procedures. Electronic medical records were used to obtain demographic information, comorbidities, smoking status, operative details (bypass target), postoperative AC/AP medications, postoperative complications, and long-term outcomes and were reviewed for the cohort. Cox proportional hazards model was used to determine independent risk factors for major adverse limb events (MALE) after bypass. MALE was defined as reintervention for patency or major amputation of index limb (above- or below-knee amputation). ResultsA total of 1421 patients underwent femoropopliteal bypass between 1995 and 2020 throughout five institutions included in this study. Complete data were available for 1292 of the 1421 patients (90.9%). The indications for bypass included intermittent claudication (21.4%), rest pain (30.3%), tissue loss (33.5%), and nonatherosclerotic disease (14.8%). Distal bypass targets comprised above-knee (38.6%) and below-knee (61.4%) popliteal arteries. Patients were divided into six groups based on postoperative AC/AP use including none (n = 57 [4.4%]), monoantiplatelet therapy (n = 587 [45.4%]), dual AP therapy (n = 214 [16.6%]), AC alone (n = 73 [5.7%]), AC + monoantiplatelet therapy (n = 319 [24.7%]), and AC + dual AP therapy (n = 42 [3.3%]). Postoperative bleeding complications were low for both hematoma (3.7%) and pseudoaneurysm (0.7%). There was no difference in bleeding complications across AC/AP groups (hematoma, P = .61; pseudoaneurysm, P = .31). After adjusting for patient factors, below-knee bypass target (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.52; P = .019) and bypass for tissue loss (HR, 1.40; 95% CI, 1.04-1.88; P = .028) were independent predictors for MALE. Great saphenous vein conduit trended toward protection for MALE, compared with prosthetic grafts (HR, 0.84; 95% CI, 0.70-1.01; P = .06). No AC/AP regimen was associated with of MALE, even stratifying by above-knee and below-knee bypass cohorts. The median follow-up period was 2 years. ConclusionsAmong patients undergoing femoropopliteal bypass grafting, no combination of AC or AP medications was associated with improved graft patency; however, a below-knee target and tissue loss were associated with adverse limb events. AC and AP regimen may be individualized after bypass with regard to other concomitant medical comorbidities.