Association of prior epidemiologic exposures with cytogenetic risk in adult acute myeloid leukemia (AML).

7047 Background: In addition to secondary AML (sAML), important lifestyle and environmental exposures associated with increased risk of AML development have been identified in recent case-control studies including obesity (BMI>30kg/m2), smoking, regular acetaminophen use, and rural/farm habitat. The association of these exposures with AML cytogenetic risk groups is unknown. We therefore evaluated relevant exposures in a cohort of 301 AML patients with confirmed central cytogenetics analysis diagnosed and treated at Mayo Clinic FL and AZ since 1995. Methods: Documented patient exposures were extracted from central electronic medical records, including: prior chemotherapy/radiation or hematologic malignancy, occupation, select medications, “toxins” (esp. benzene) and solid organ transplantation (SOT). Standard cytogenetic risk categories (including intermediate abnormal) were applied. The association of epidemiologic exposures with cytogenetic risk was evaluated on multivariable analysis using logistic regression models. Results: sAML was significantly associated with cytogenetic risk groups, as was prior SOT, healthcare occupation, farm habitat and toxin exposures [see Odds Ratios (OR), Table). In contrast, prior radiation for epithelial malignancies, smoking and BMI were not independently associated with specific cytogenetic risk categories. Conclusions: Specific epidemiologic exposures are significantly associated with AML cytogenetic risk categories suggesting a unique clinical phenotype. This supports a link to leukemogenesis and requires validation in a controlled prospective therapeutic study. [Table: see text]

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Solid Organ Transplantation (SOT) and Data Mining: Bloodstream Infections (BSI) Have a Significant Impact on One-Year Survival, and qSOFA ≥ 2 Predicts 30-Day Mortality

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx162.025 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S10-S10

Author(s):

Terrence Liu ◽

Donglu Xie ◽

Beverley Adams-Huet ◽

Jade Le ◽

Christina Yek ◽

...

Keyword(s):

Risk Factors ◽

Data Mining ◽

Cumulative Incidence ◽

Multivariable Analysis ◽

Solid Organ Transplantation ◽

Common Source ◽

Solid Organ ◽

Risk Of Death ◽

Increased Risk ◽

Mining Tools

Abstract Background We created a retrospective and prospective database of SOT recipients using innovative data mining tools. This study describing the epidemiology of BSI in SOT serves as a proof of concept of such techniques in clinical research. Methods The design of the study was a retrospective, single-center, cohort study. Data mining tools were used to extract information from the electronic medical record and merged it with data from the SRTR (Figure 1). First SOT from January 1, 2010 to December 31, 2015 were included. Charts of subjects with positive blood cultures were manually reviewed and adjudicated using CDC/NHSN and SCCM/ESICM criteria. The 1-year cumulative incidence was calculated using the Kaplan–Meier method. Cox proportional hazards models were used to identify risk factors for BSI and 1-year mortality. BSI was analyzed as a time-dependent covariate in the mortality model. Fisher’s exact test and chi-square were used to identify risk factors for 30-day mortality and MDRO. Results A total of 917 SOT recipients met inclusion criteria. Seventy-five patients experienced at least one BSI. The cumulative incidence was 8.4% (95% CI 6.8–10.4) (Figure 2). The onset of the first BSI episode was: 30 episodes (40%) <1 month, 33 (44%) 1–6 months, and 12 (16%) >6 months. The most common pathogens were Klebsiella sp. (16%), Vancomycin-resistant E. faecium (12%), E. coli (12%), CoNS (12%), and Candida sp. (9.3%). Nineteen isolates (25%) were identified as MDRO; the risk of MDRO was highest <1 month compared with 1–6 and >6 months (44.8 vs. 12.1 vs. 16.7; P = 0.01). The most common source of BSI was CLABSI (29%) (Figure 3). In multivariable analysis, the risk of BSI was associated with organ type (HR [95% CI] = Multiorgan 3.5 [1.1–11.6], liver 2.5 [1.1–5.4], heart 2.4 [1.1–5.1]) and acquisition of a BSI was associated with a higher 1-year mortality (HR = 8.7 [5.1–14.7]). In univariable analysis, a polymicrobial BSI (14.7 vs. 57.1%; P = 0.02), qSOFA ≥ 2 (0.0 vs. 25.5%; P = 0.02) and septic shock (3.9 vs. 52.2%; P < 0.001) were associated with an increased risk of death at 30 days. Conclusion A BSI significantly affects the 1-year survival of SOT recipients. A qSOFA ≥ 2 can be used to identify patients at risk for death. Additionally, this study illustrates the potential of data mining tools to study infectious complications. Disclosures All authors: No reported disclosures.

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Exploring the Epidemiology of Cancer after Solid Organ Transplantation (EpCOT): an observational cohort study

BMJ Open ◽

10.1136/bmjopen-2020-043731 ◽

2021 ◽

Vol 11 (4) ◽

pp. e043731

Author(s):

Adnan Sharif ◽

Javeria Peracha ◽

David Winter ◽

Raoul Reulen ◽

Mike Hawkins

Keyword(s):

Organ Transplantation ◽

Record Linkage ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Study Cohort ◽

Solid Organ ◽

Post Transplantation ◽

Increased Risk ◽

Risk Of Cancer

IntroductionSolid organ transplant patients are counselled regarding increased risk of cancer (principally due to their need for lifelong immunosuppression) and it ranks as one of their biggest self-reported worries. Post-transplantation cancer is common, associated with increased healthcare costs and emerging as a leading cause of post-transplant mortality. However, epidemiology of cancer post-transplantation remains poorly understood, with limitations including translating data from different countries and national data being siloed across different registries and/or data warehouses.Methods and analysisStudy methodology for Epidemiology of Cancer after Solid Organ Transplantation involves record linkage between the UK Transplant Registry (from NHS Blood and Transplant), Hospital Episode Statistics (for secondary care episodes from NHS Digital), National Cancer Registry (from cancer registration data hosted by Public Health England) and the National Death Registry (from NHS Digital). Deterministic record linkage will be conducted by NHS Digital, with a fully anonymised linked dataset available for analysis by the research team. The study cohort will consist of up to 85 410 solid organ transplant recipients,who underwent a solid organ transplant in England between 1 January 1985 and 31 December 2015, with up-to-date outcome data.Ethics and disseminationThis study has been approved by the Confidentiality Advisory Group (reference: 16/CAG/0121), Research Ethics Committee (reference: 15/YH/0320) and Institutional Review Board (reference: RRK5471). The results of this study will be presented at national and international conferences, and manuscripts with results will be submitted for publication in high-impact peer-reviewed journals. The information produced will also be used to develop national evidence-based clinical guidelines to inform risk stratification to enable risk-based clinical follow-up.Trial registration numberNCT02991105.

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Adiponectin Associates with Rheumatoid Arthritis Risk in Overweight and Obesity Independently of Other Adipokines

Journal of Clinical Medicine ◽

10.3390/jcm10132791 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2791

Author(s):

Yuan Zhang ◽

Linda Johansson ◽

Johanna Andersson-Assarsson ◽

Magdalena Taube ◽

Markku Peltonen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Multivariable Analysis ◽

Overweight And Obesity ◽

Northern Sweden ◽

Case Control Studies ◽

Rheumatoid Arthritis Risk ◽

Increased Risk ◽

Obese Subjects ◽

Nested Case Control

We recently reported that increased serum adiponectin was associated with rheumatoid arthritis (RA) risk in subjects with obesity. We hereby aim to determine if other adipokines associate with RA risk and if the association between adiponectin and RA is independent of other adipokines. Two nested-case control studies were performed in two different cohorts: 82 participants of the Swedish Obese Subjects (SOS) study who developed RA during follow-up matched with 410 controls, and 88 matched pairs from the Medical Biobank of Northern Sweden. Baseline levels of circulating adipokines were measured using ELISA. In a multivariable analysis in the SOS cohort, higher adiponectin was associated with an increased risk of RA independently of other adipokines (OR for RA risk: 1.06, 95% CI: 1.01–1.12, p = 0.02). No association between leptin, resistin, and visfatin levels and the risk of RA was detected. In the cohort from the Medical Biobank of Northern Sweden, higher adiponectin was associated with an increased risk of RA only in participants with overweight/obesity (OR: 1.17, 95% CI: 1.01−1.36, p = 0.03), independently of other adipokines. Our results show that in individuals with overweight/obesity, higher circulating levels of adiponectin, but not leptin, resistin, or visfatin, were associated with an increased RA risk.

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1171. Lower Mortality with Adjuvant Corticosteroid Therapy in non-HIV Infected Patients with pneumocystis jirovecii pneumonia: A Single US Cohort Study and a Proposed Novel Mechanism of Corticosteroids

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1357 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S610-S611

Author(s):

William Mundo ◽

Carlos Franco-Paredes ◽

Steven C Johnson ◽

Leland Shapiro ◽

Andres Henao-Martinez

Keyword(s):

Corticosteroid Therapy ◽

Multivariable Analysis ◽

Solid Organ Transplantation ◽

Pneumocystis Jirovecii ◽

Lower Mortality ◽

Pneumocystis Jirovecii Pneumonia ◽

Solid Organ ◽

Hiv Status ◽

Predictors Of Mortality ◽

Hiv Negative

Abstract Background Pneumocystis jirovecii pneumonia (PJP) remains a cause of mortality in HIV-negative patients. The clinical benefit of adjuvant corticosteroids given at the time of PJP antimicrobial therapy in these patients is uncertain. This study aimed to determine if corticosteroids reduced mortality in a cohort of HIV-negative PJP patients, and to propose a novel mechanism explaining corticosteroid benefit in patients regardless of HIV status. Methods We examined a retrospective case series of patients diagnosed with PJP at the University of Colorado Hospital between 1995-2019. Data were collected in 71 PJP-infected patients. Twenty-eight patients were HIV-negative, and 43 were infected with HIV. We performed bivariate and forward, stepwise multivariable logistic regressions to identify predictors of mortality. Results Underlying conditions in HIV-negative patients were hematologic malignancies (28.6%), autoimmune disorders (25.9%), or solid organ transplantation (10.7%). Compared to HIV-positive patients, HIV-negative patients had higher rates and duration of mechanical ventilation and ICU stay. Survival was significantly increased in HIV-negative patients receiving adjunct corticosteroids, with 100% mortality in patients not receiving corticosteroids vs 60% mortality in patients receiving corticosteroids (p=0.034). In an adjusted multivariable model, corticosteroids were associated with lower mortality (OR 13.5, 95% CI: 1.1-158.5, p= 0.039) regardless of HIV status. In a novel model of adjunct corticosteroid benefit, we propose corticosteroids reduce immune-mediated lysis of Pneumocystis organisms that curtails the surfactant-disabling effect of PJP internal contents. Table 1. Multivariable Analysis of Predictors of Mortality in patients with PJP Figure 1. Mortality differences by HIV status and use of steroids in PJP Conclusion We found substantial mortality among HIV-negative patients with PJP and adjunct corticosteroid use was associated with decreased mortality. Adjunct corticosteroid mortality-lowering effect is best explained by suppressing pneumocystis lysis. This reduces surfactant disruption resulting from pneumocystis internal substances. Figure 2. Proposed mechanism of action for benefits of adjunct exogenous corticosteroid therapy during PJP Disclosures All Authors: No reported disclosures

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Viral Enteritis in Solid-Organ Transplantation

Viruses ◽

10.3390/v13102019 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2019

Author(s):

Anum Abbas ◽

Andrea J. Zimmer ◽

Diana Florescu

Keyword(s):

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Post Transplantation ◽

Organ Transplant Recipients ◽

Increased Risk ◽

Viral Enteritis ◽

Solid Organ Transplant Recipients

Solid organ transplant recipients are at increased risk for infections due to chronic immunosuppression. Diarrhea is a commonly encountered problem post transplantation, with infectious causes of diarrhea being a frequent complication. Viral infections/enteritides in solid organ transplant recipients often result from frequently encountered pathogens in this population such as cytomegalovirus, adenovirus, and norovirus. However, several emerging viral pathogens are increasingly being recognized as more sensitive diagnostic techniques become available. Treatment is often limited to supportive care and reduction in immunosuppression, though antiviral therapies mayplay a role in the treatment in certain diseases. Viral enteritis is an important entity that contributes to morbidity and mortality in transplant recipients.

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Herpes Zoster in Solid Organ Transplantation: Incidence and Risk Factors

Frontiers in Immunology ◽

10.3389/fimmu.2021.645718 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marcia M. L. Kho ◽

Stefan Roest ◽

Dominique M. Bovée ◽

Herold J. Metselaar ◽

Rogier A. S. Hoek ◽

...

Keyword(s):

Risk Factors ◽

Herpes Zoster ◽

Multivariable Analysis ◽

Solid Organ Transplantation ◽

Organ Transplant ◽

Clinical Signs ◽

Significant Risk ◽

Solid Organ ◽

Disseminated Disease ◽

Cmv Prophylaxis

BackgroundStudies on herpes zoster (HZ) incidence in solid organ transplant (SOT) recipients report widely varying numbers. We investigated HZ incidence, severity, and risk factors in recipients of four different SOTs, with a follow-up time of 6–14 years.MethodsRecords of 1,033 transplant recipients after first heart (HTx: n = 211), lung (LuTx: n = 121), liver (LiTx: n = 258) and kidney (KTx: n = 443) transplantation between 2000 and 2014 were analyzed for VZV-PCR, clinical signs of HZ, and complications.ResultsHZ was diagnosed in 108 of 1,033 patients (10.5%): 36 HTx, 17 LuTx, 15 LiTx, and 40 KTx recipients. Overall HZ incidence rate after HTx (30.7 cases/1,000 person–years (PY)), LuTx (38.8 cases/1,000 PY), LiTx (22.7 cases/1,000 PY) and KTx (14.5 cases/1,000 PY) was significantly higher than in the general 50–70 year population. Multivariable analysis demonstrated age ≥50 years at transplantation (p = 0.038, RR 1.536), type of organ transplant (overall p = 0.002; LuTx p = 0.393; RR 1.314; LiTx p = 0.011, RR 0.444; KTx p = 0.034, RR 0.575), CMV prophylaxis (p = 0.043, RR 0.631) and type of anti-rejection therapy (overall p = 0.020; methylprednisolone p = 0.008, RR 0.475; r-ATG p = 0.64, RR1.194) as significant risk factors. Complications occurred in 33 of 108 (31%) patients (39% of HTx, 47% of LuTx, 20% of LiTx, 20% of KTx): post-herpetic neuralgia, disseminated disease, and cranial nerve involvement.ConclusionHZ incidence and severity in SOT recipients are most pronounced after heart and lung transplantation, in older patients, and when CMV prophylaxis is lacking.

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Factors Associated With Ventriculoperitoneal Shunt Placement in Patients With Cryptococcal Meningitis

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz241 ◽

2019 ◽

Vol 6 (6) ◽

Cited By ~ 2

Author(s):

John W Baddley ◽

George R Thompson ◽

Kristen O Riley ◽

Mary K Moore ◽

Stephen A Moser ◽

...

Keyword(s):

Cryptococcal Meningitis ◽

Multivariable Analysis ◽

Solid Organ Transplantation ◽

Categorical Variables ◽

Stepwise Logistic Regression ◽

Fisher Exact Test ◽

Solid Organ ◽

Vp Shunt ◽

Factors Associated ◽

Shunt Placement

Abstract Objective Increased intracranial pressure (ICP) is an important complication of cryptococcal meningitis (CM) and impacts morbidity and mortality. Factors associated with permanent ventriculoperitoneal (VP) shunt placement are poorly characterized. Method We conducted a retrospective cohort study of patients with CM at the University of Alabama at Birmingham from 1996 through 2015. Characteristics of patients at time of CM diagnosis who did and did not receive a VP shunt were compared with use of the 2-group chi-square test or Fisher exact test for categorical variables and the 2-group t test for continuous variables. Stepwise logistic regression analysis was used to determine predictors of shunt placement. Results Of 422 patients with cryptococcosis, 257 (60.9%) had CM. Mean age was 47.7 years, 71.6% were male, and 44.4% were African American. The most common underlying conditions were HIV (42.4%), solid organ transplantation (29.6%), and corticosteroid use (34.2%). Forty-four (17.1%) received a VP shunt a median of 17 days (range, 1–320 days) post-diagnosis. By multivariable analysis, baseline opening pressure >30 cm H2O (OR, 9.4; 95% CI, 3.0, 28.8; P < .0001), being a normal host (OR, 6.3; 95% CI, 1.5, 26.1; P = .011) and hydrocephalus (OR, 4.9, 95% CI, 1.3, 17.9); P = .017) were associated with increased odds of shunting (Table 2). In contrast, age (OR, 0.96; 95% CI, 0.92, 0.99; P = .037) and male gender (OR, 0.18; 95% CI, 0.06, 0.55; P = .023) were associated with decreased odds of shunting. Conclusions Identification of factors at time of CM diagnosis associated with need for permanent VP shunt placement may allow for earlier, more aggressive treatment and potentially improve outcomes associated with increased ICP from cryptococcal meningitis.

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A Prognostic Model for Predicting the Impact of Comorbidities on Survival of Patients with Myelodysplastic Syndromes.

Blood ◽

10.1182/blood.v110.11.2453.2453 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2453-2453 ◽

Cited By ~ 1

Author(s):

Matteo G. Della Porta ◽

Luca Malcovati ◽

Erica Travaglino ◽

Cristiana Pascutto ◽

Margherita Maffioli ◽

...

Keyword(s):

Heart Failure ◽

Iron Overload ◽

Myelodysplastic Syndromes ◽

Cardiac Death ◽

Multivariable Analysis ◽

Risk Groups ◽

Increased Risk ◽

Secondary Iron Overload ◽

Transfusion Dependency ◽

The Impact

Abstract Myelodysplastic syndromes (MDS) occur mainly in older persons, and these patients are likely to have comorbidities. We studied the impact of comorbidities on non-leukemic death (NLD) and overall survival (OS) in MDS patients with the aim of developing a specific prognostic index. Eight hundred forty consecutive patients receiving a diagnosis of MDS at Policlinico San Matteo, Pavia, Italy, between 1992 and 2006 were retrospectively evaluated. One or more comorbidities were present in 455/840 (54%) patients: the older the age, the higher their prevalence (P<0.001). Cardiac disease was observed in 25% of patients, liver disease in 16%, diabetes in 11%, prior solid tumor in 10%, nephropathy and pulmonary disease in 4%. Non-leukemic causes of death included cardiac failure (63%), infection (24%) and hemorrhage (7%). In a Cox analysis with age, sex, WHO category, cytogenetics and transfusion-dependency as time-dependent covariates, the presence of one or more comorbidities significantly affected both the risk of NLD (HR=1.91, P=0.001) and OS (HR=1.51, P=0.01), while it did not influence the risk of leukemic progression. The negative effect of comorbidities on OS was more evident in patients without excess of blasts (HR=1.8 P=0.007), while it retained a borderline significance in patients with more advanced disease (P=0.05). By including comorbidities as distinct entities in multivariable analysis, cardiac failure, liver or pulmonary disease, and solid tumors were found to independently affect the risk of NLD (HR=3.7, HR=2.08, HR=2.07 HR=2.23, respectively; P values from <0.001 to 0.033). Based on results of uni- and multivariable analysis, we developed a prognostic model for predicting the effect of comorbidities on NLD and OS. For each comorbidity, risk scores were estimated from the coefficients of the Cox regression. This MDS-specific comorbidity index (MDS-CI) allowed us to identify 3 groups of patients with different probability of NLD and OS (HR 2.78, P<0.001; HR 1.67 P=0.001), and provided a better stratification than the available non MDS-specific indices. Focusing on WPSS categories [J Clin Oncol2007; 25:3503–10], MDS-CI significantly stratified survival of patients with very-low, low and intermediate risk groups (P<0.001), while it had no effect in high and very-high risk groups. We then investigated the relationship between transfusion-dependency, secondary iron overload and comorbidities. Heart failure (28% vs. 18% P=0.001) and cardiac death (69% vs 55% P=0.03) were significantly more frequent in transfusion-dependent patients. In a Cox analysis with time-dependent covariates, transfusion-dependent patients showed an increased risk of NLD (HR=2.12 P=<0.001), heart failure (HR 1.34 P=0.03), and cardiac death (HR 2.99 P=0.01). The development of secondary iron overload significantly affected the risk of NLD and OS (HR=1.25 and 1.16 respectively, P<0.001), and this effect was maintained after adjusting for transfusion burden. Iron overload specifically increased the risk of developing heart failure (HR=1.17, P<0.001). In summary, the presence of non-hematological comorbidities significantly worsens the survival of MDS patients. Transfusion-dependency and secondary iron overload are associated with an increased risk of cardiac complications and cardiac death. The MDS-CI might be a useful tool for clinical decision making in patients with myelodysplastic syndromes.

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Assessing interactions between HLA-DRB1*15 and infectious mononucleosis on the risk of multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513477231 ◽

2013 ◽

Vol 19 (10) ◽

pp. 1355-1358 ◽

Cited By ~ 8

Author(s):

Giulio Disanto ◽

Carolina Hall ◽

Robyn Lucas ◽

Anne-Louise Ponsonby ◽

Antonio J Berlanga-Taylor ◽

...

Keyword(s):

Multiple Sclerosis ◽

Infectious Mononucleosis ◽

Additive Model ◽

Causal Process ◽

Case Control Studies ◽

Logistic Regression Models ◽

Gene Environment ◽

Increased Risk ◽

History Of ◽

Additive Scale

Gene–environment interactions may shed light on the mechanisms underlying multiple sclerosis (MS). We pooled data from two case-control studies on incident demyelination and used different methods to assess interaction between HLA-DRB1*15 (DRB1-15) and history of infectious mononucleosis (IM). Individuals exposed to both factors were at substantially increased risk of disease (OR=7.32, 95% CI=4.92–10.90). In logistic regression models, DRB1-15 and IM status were independent predictors of disease while their interaction term was not (DRB1-15*IM: OR=1.35, 95% CI=0.79–2.23). However, interaction on an additive scale was evident (Synergy index=2.09, 95% CI=1.59–2.59; excess risk due to interaction=3.30, 95%CI=0.47–6.12; attributable proportion due to interaction=45%, 95% CI=22–68%). This suggests, if the additive model is appropriate, the DRB1-15 and IM may be involved in the same causal process leading to MS and highlights the benefit of reporting gene–environment interactions on both a multiplicative and additive scale.

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Scedosporiosis in a Combined Kidney and Liver Transplant Recipient: A Case Report of Possible Transmission from a Near-Drowning Donor

Case Reports in Transplantation ◽

10.1155/2016/1879529 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Rachael Leek ◽

Erika Aldag ◽

Iram Nadeem ◽

Vikraman Gunabushanam ◽

Ajay Sahajpal ◽

...

Keyword(s):

Solid Organ Transplantation ◽

Organ Transplant ◽

Solid Organ ◽

Transplant Recipients ◽

Near Drowning ◽

Saprobic Fungi ◽

Increased Risk ◽

Serious Infections ◽

Solid Organ Transplant Recipients ◽

Immunocompromised Hosts

Scedosporium spp. are saprobic fungi that cause serious infections in immunocompromised hosts and in near-drowning victims. Solid organ transplant recipients are at increased risk of scedosporiosis as they require aggressive immunosuppression to prevent allograft rejection. We present a case of disseminated Scedosporium apiospermum infection occurring in the recipient of a combined kidney and liver transplantation whose organs were donated by a near-drowning victim and review the literature of scedosporiosis in solid organ transplantation.

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