Higher Risk Of Serious Infections Research Articles

Design and development of advanced glucose biosensors via tuned interactions between marine polysaccharides and diagnostic elements – A survey

Extensive scientific analysis on the susceptibility of different populations to COVID-19 highlights that compared to populations with no co-morbidities, people with co-morbidities such as diabetes mellitus (DM) are at a significantly higher risk of serious infection, hospitalization, or even death. This underscores the importance of controlling DM through self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) using biosensors. These biosensors, which can be either enzymatic or non-enzymatic, have undergone several rounds of development in terms of the materials used for device construction. In terms of the immobilization agent needed to anchor enzymatic or non-enzymatic detection elements to the electrode surface, marine polysaccharides, such as chitosan and alginate, hold a distinct advantage. This, in turn, can be ascribed to their biocompatibility, chemical stability, film-forming ability, functionality bind with enzymes/diagnostic elements, and easy availability. In this review, we focus extensively on the use of cationic chitosan and anionic alginate in the past decade for designing advanced glucose biosensors. Their role in enhancing sensor response via physical/chemical interactions with the conducting and diagnostic elements is analyzed in detail from a structural point of view. In addition, the possibility of using these polysaccharides in non-invasive CGM sensors is discussed and several potential future research avenues are presented.

Limited Utility of SIRS Criteria for Identifying Serious Infections in Febrile Young Infants.

(1) Background: Young infants have a high risk of serious infection. The Systematic Inflammatory Response Syndrome (SIRS) criteria can be useful to identify both serious bacterial and viral infections. The aims of this study were to evaluate the diagnostic performance of the SIRS criteria for identifying serious infections in febrile young infants and to identify potential clinical predictors of such infections. (2) Methods: We conducted this prospective cohort study including febrile young infants (aged < 90 days) seen at the emergency department with a body temperature of 38.0 °C or higher. We calculated the diagnostic performance parameters and conducted the logistic regression analysis to identify the predictors of serious infection. (3) Results: Of 311 enrolled patients, 36.7% (n = 114) met the SIRS criteria and 28.6% (n = 89) had a serious infection. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of the SIRS criteria for serious infection was 45.9%, 69.4%, 43.5%, 71.4%, 1.5, and 0.8, respectively. Logistic regression showed that male gender, body temperature ≥ 38.5 °C, heart rate ≥ 178 bpm, and age ≤ 50 days were significant predictors. (4) Conclusions: The performance of the SIRS criteria for predicting serious infections among febrile young infants was poor.

Abstract 719: The emergence of the COVID-19 pandemic and its impact on a novel cancer care delivery model at Federally Qualified Health Centers

Abstract Background: The emergence of COVID-19 has particularly disrupted the lives of vulnerable patients needing comprehensive care, including cancer survivors. Moreover, patients receiving immunosuppressive treatment for cancer are at heightened infection risk and when infected, cancer survivors are at higher risk of serious infection. Further complicating matters, surgeries with curative intent have been significantly limited and systemic therapies for patients with cancer have been delayed to minimize patient and staff exposure to SARS-CoV-2. Preexisting gaps in cancer screening, treatment, and follow up as well as in the monitoring of primary care needs for patients at Federally Qualified Health Centers (FQHCs) have become more apparent due to the COVID-19 pandemic. The 4R model (Right information and Right Care for the Right Patient at the Right Time) is a novel approach our team developed to facilitate cancer planning, as a vehicle for patient enablement and team-based care delivery across the oncology and primary care continuum. The innovative cancer care delivery model has been successfully implemented and used in a pre-COVID setting. The COVID-19 pandemic provides an urgent need to study the ways in which preexisting cancer care delivery models have been disrupted and to adapt processes in order to provide quality care. Methods: Semi-structured interviews are being conducted with clinical care team members (N=10), patients (N=25), family/caregivers (N=10), and community organizations (N=5) in order to identify areas in which care for patients with cancer in a primary care setting have changed and how clinics are adapting to their patients' needs in the setting of the COVID-19 pandemic. A Rapid analysis process, which is a qualitative analysis method recommended for circumstances in which a quick analysis is required to adopt changes to an ongoing process, will be utilized. Results: Preliminary results from stakeholder feedback and clinical care team interviews have revealed changes in the FQHC's approach to cancer care coordination during the COVID-19 pandemic. In the spring/early summer of 2020, clinical team members were overburdened with clinical operation changes and the need to swiftly re-allocate resources towards COVID-19 testing. Non-emergent appointments transitioned to telehealth and care coordinators, the keystone of the 4R model, were working remotely and were met with significant obstacles in referring cancer survivors to specialty care and community resources. Conducting additional interviews will help elucidate the receptivity of the recently implemented 4R cancer care delivery model and inform how telehealth can be harnessed during this time to meet the complex needs and coordinating care for patients with cancer. Citation Format: Nicolas Francone, Will Dunne, Jonathan Alhalel, Sankirtana Danner, Nihmotallahi Adebayo, T Madorsky, Cassandra Osei, Juan Rivera, J Trossman, Christine Weldon, Elizabeth Adetoro, Melissa Simon. The emergence of the COVID-19 pandemic and its impact on a novel cancer care delivery model at Federally Qualified Health Centers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 719.

Giant cell arteritis treatment patterns and rates of serious infections.

Giant cell arteritis (GCA) afflicts older adults who may have age- and comorbidity-related risks for infection and is treated with immunosuppressants that increase risk of infection. We examined GCA treatment patterns and rates of serious infections in two real-world cohorts in the U.S. We identified two GCA cohorts using two U.S. health insurance databases, Medicare (public, 2007-2017) and MarketScan (commercial, 2015-2019), by applying a validated claims-based algorithm with positive predictive value 79.0% for GCA. We required age ≥50 years and assessed baseline comorbidities, dispensing of immunosuppressants and prophylactic antibiotics, and vaccine administration. We calculated incidence rates (IR) of serious infections, defined as bacterial or viral infections requiring hospitalisation based on primary inpatient diagnosis code. Multivariable Cox proportional hazards models estimated hazard ratios for risk of serious infection for prespecified covariates. The Medicare cohort included 734 patients, 28% male, mean age 77.1; the MarketScan cohort included 1022 patients, 30% male, mean age 68.4. More than 85% used prednisone ≥60mg daily at index date and <10% used tocilizumab. Serious infections developed in 27.9% of Medicare and 7.2% of MarketScan patients: IR per 100 person-years = 10.7 (95% CI 9.3, 12.2) in Medicare and 6.3 (95% CI 5.0, 7.9) in MarketScan. Older age and higher frailty score were significantly associated with increased risk for serious infection. In these two U.S. GCA cohorts, high-dose glucocorticoids were the most common initial treatment, and over 25% of Medicare and 7% of MarketScan patients developed serious infection during follow-up. Older age and higher frailty score were associated with higher risk of serious infections, though maximum daily prednisone dose was not. Pneumocystis jiroveci pneumonia was rare in two GCA cohorts despite infrequent use of prophylactic antibiotics.

Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients

Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population. This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children. This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab. The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P= .009), hypo-IgA (11.1%-20.4%; P= .02), and hypo-IgM (20.0%-62.0%; P< .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P= .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias. Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.

Morbidity and mortality in adult-onset IgA vasculitis: a long-term population-based cohort study.

With sparse data available, we investigated mortality and risk factors in adults with IgA vasculitis (IgAV). This was an observational population-based cohort study using state-wide linked longitudinal health data for hospitalized adults with IgAV (n = 267) and matched comparators (n = 1080) between 1980 and 2015. Charlson comorbidity index (CCI) and serious infections (SIs) were recorded over an extensive lookback period prior to diagnosis. Date and causes of death were extracted from the Western Australia Death Registry. Mortality rate (deaths/1000 person-years) ratios (MRRs) and hazard ratio (HR) for survival were assessed. During 9.9 (9.8) years lookback patients with IgAV accrued higher CCI scores (2.60 vs 1.50, P < 0.001) and had higher risk of SI (OR = 8.4, P < 0.001), not fully explained by CCI scores. During 19 years' follow-up, the rate of death in patients with IgAV (n = 137) was higher than in comparators (n = 397) (MRR = 2.06, 95% CI: 1.70-2.50; P < 0.01) and the general population (standardized mortality rate ratio = 5.64, 95% CI: 4.25, 7.53; P < 0.001). Survival in IgAV was reduced at 5 (72.7 vs 89.7%) and 20 years (45.2% vs 65.6%) (both P < 0.05). CCI (HR = 1.88, 95% CI: 1.25, 2.73; P = 0.001), renal failure (HR = 1.48, 95% CI: 1.04, 2.22; P = 0.03) and prior SI (HR = 1.48, 95% CI: 1.01, 2.16; P = 0.04) were independent risk factors. Death from infections (5.8 vs 1.8%, P = 0.02) was significantly more frequent in patients with IgAV. Premorbid comorbidity accrual appears increased in hospitalized patients with IgAV and predicts premature death. As comorbidity does not fully explain the increased risk of premorbid infections or the increased mortality due to infections in IgAV, prospective studies are needed.

Frailty and Risk of Serious Infections in Biologic-treated Patients With Inflammatory Bowel Diseases.

Identifying biologic-treated patients with inflammatory bowel diseases (IBDs) at higher risk of serious infections is a priority. We conducted a retrospective cohort study evaluating frailty and risk of serious infections in biologic-treated patients with IBD. Using an administrative claims database, we identified biologic-treated patients with IBD between 2014 and 2018 with follow-up 1 year before and after treatment initiation. Using a validated claims-based hospital frailty risk scoring system, patients were classified as frail and nonfrail. We compared the risk of serious infections (infections requiring hospitalization) between frail and nonfrail patients using Cox proportional hazard analysis adjusting for age, comorbidities, disease characteristics, health care utilization, use of corticosteroids, immunomodulators, and opiates. We included 5987 biologic-treated patients with IBD (4881 on TNFα antagonists, 1106 on vedolizumab), of whom 2350 (39.3%) were classified as frail; over 7115 person-years of follow-up was included, and 520 patients developed serious infection. Frailty was not associated with increased risk of serious infection (adjusted hazard ratio [aHR], 1.12; 95% CI, 0.93-1.36), whereas advanced age (older than 60 years), high comorbidity burden, corticosteroid use, opiate use, and prior serious infection were associated with increased risk of serious infection. On stratified analysis, frailty was associated with increased risk of serious infections in vedolizumab-treated patients (aHR, 1.69; 95% CI, 1.03-2.79) but not in TNFα antagonist-treated patients (aHR, 1.03; 95% CI, 0.83-1.27). In biologic-treated patients with IBD, frailty assessed using a claims-based frailty index was not independently associated with increased risk of serious infections. Future studies evaluating objective and biological measures of frailty are warranted to risk-stratify older patients with IBD.

S0861 Comparative Risk of Serious Infections With Tumor Necrosis Factor-α Antagonists vs Vedolizumab in Patients With Inflammatory Bowel Diseases

INTRODUCTION: Comparative safety of therapies is an important attribute in choosing optimal therapy in patients with inflammatory bowel diseases (IBD). We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-α (TNFα) antagonists and those treated with vedolizumab. METHODS: Using an administrative claims database (OptumLabs Data Warehouse) we identified patients with IBD who were new-users of either TNFα antagonists or vedolizumab between 2014 and 2019 and had insurance coverage for at least 1y before and 1y after treatment initiation. We compared the risk of serious infections between patients treated with TNFα antagonists and those treated with vedolizumab using marginal structural Cox proportional hazard models adjusted for ulcerative colitis (UC) versus Crohn’s disease (CD), baseline demographics, healthcare utilization, comorbidities and time-varying use of IBD-related medications including corticosteroids and immunomodulators. RESULTS: We included 4896 patients treated with TNFα antagonists (age, 41 ± 15 y, 51% male, 60% with CD) of whom 434 developed serious infections over a 6009 person-year [py] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16 y, 49% male, 39% with CD) of whom 86 developed serious infections over a 1077 py follow-up. On adjusted analysis, TNFα antagonists were associated with 2.4-fold higher risk of serious infections (hazard ratio [HR], 2.38 [95% CI, 1.38–4.13]) when compared with vedolizumab in all patients with IBD, and in subgroup analyses of patients with CD (HR, 2.28 [1.13–4.62]) and UC (HR, 1.62 [1.03–2.5]). This was primarily driven by increased risk of extra-intestinal serious infections (HR, 3.13 [1.48–6.63]), without any increase in risk of serious gastrointestinal infections (HR, 0.60 [0.33–1.08]). CONCLUSION: In a large claims-based study, TNFα antagonists were associated with increased risk of serious infections as compared with vedolizumab, in patients with CD and UC, particularly risk of extra-intestinal infections.

Intravenous Iron or Red Blood Cell Supplementation and Risk of Serious Infection in Left Ventricular Assist Device Patients

Introduction Patients with durable left ventricular assist devices (LVADs) are at high risk for serious infection and associated mortality. Furthermore, these patients also have a high prevalence of iron deficiency due to ongoing hemolysis, increased propensity for gastrointestinal bleeding, and dysregulated iron metabolism that accompanies mechanical circulatory support and heart failure. Intravenous (IV) iron-related supplementation [IVIRS, including IV iron infusion or red blood cell transfusion (RBC)] has been hypothesized to increase risk of infection. Hypothesis IVIRS (IV iron infusion or RBC transfusion) is associated with an increased risk of serious infection in LVAD patients. Methods This is a single center, retrospective, observational cohort study of 211 consecutive adult patients [median age 57.2 years (25th-75th percentile: 48.7-65.7 years), 19% female] who were discharged and followed after de-novo LVAD implantation between May 2008 and December 2019. Patients were followed until either end of the study period, or occurrence of death, heart transplantation, or LVAD removal/replacement, whichever came first. All administration of IVIRS and diagnosis of serious infection after discharge from index hospitalization was abstracted from the electronic medical record. Serious infection was defined as the first incident infection requiring hospitalization, divided into LVAD-associated infections (pump/cannula, pocket or driveline infection) and non-LVAD infections. Multivariate logistic regression was used to examine the association between IVIRS and serious infections. Results Over a median follow-up of 15.2 months (25th-75th percentile: 6.9-29.4 months), 69 (33%) LVAD patients received IVIRS, of whom 47 (68%) received IV iron and 44 (64%) received RBC transfusion. During follow-up, 87 (41%) patients suffered a serious infection, of which 48 (55%) were LVAD-associated infections and 39 (45%) were non-LVAD infections. After adjustment for age, sex, diabetes, chronic kidney disease, prior cardiac surgery, destination therapy and pre-IVIRS serious infection, LVAD patients who received IVIRS had 2.85 times higher odds of any first serious infection compared to those who did not receive IVIRS during the study period (95% CI 1.49-5.46, p=0.002). Patients who received IVIRS had a significant 3.03 times greater odds of non-LVAD infection (95% CI 1.37-6.70, p=0.006) and a non-significant 1.54 times greater odds of LVAD infection (95% CI 0.75-3.18, p=0.24), compared to LVAD patients who did not receive IVIRS. Conclusion IVIRS use is associated with a higher risk of serious infection in LVAD patients, primarily due to serious non-LVAD infections. These findings merit further study in larger cohorts and randomized trials to determine best practices surrounding IVIRS in LVAD patients.

Anti-tumor necrosis factor therapy in patients with inflammatory bowel disease; comorbidity, not patient age, is a predictor of severe adverse events

PurposeTo assess safety and effectiveness of anti-tumor necrosis factor (anti-TNF) therapy in IBD patients ≥ 60 years.MethodsNinety IBD patients ≥ 60 years at initiation of anti-TNF therapy, 145 IBD patients ≥ 60 years without anti-TNF therapy and 257 IBD patients < 60 years at initiation of anti-TNF therapy were retrospectively included in this multicentre study. Primary outcome was the occurrence of severe adverse events (SAEs), serious infections and malignancies. Secondary outcome was effectiveness of therapy. Cox regression analyses were used to assess differences in safety and effectiveness. In safety analyses, first older patients with and without anti-TNF therapy and then older and younger patients with anti-TNF therapy were assessed.ResultsIn older IBD patients, the use of anti-TNF therapy was associated with serious infections (aHR 3.920, 95% CI 1.185–12.973, p = .025). In anti-TNF-exposed patients, cardiovascular disease associated with serious infections (aHR 3.279, 95% CI 1.098–9.790, p = .033) and the presence of multiple comorbidities (aHR 9.138 (1.248–66.935), p = .029) with malignancies, while patient age did not associate with safety outcomes. Effectiveness of therapy was not affected by age or comorbidity.ConclusionOlder patients receiving anti-TNF therapy have a higher risk of serious infections compared with older IBD patients without anti-TNF therapy, but not compared with younger patients receiving anti-TNF therapy. However, in anti-TNF-exposed patients, comorbidity was found to be an indicator with regards to SAEs. Effectiveness was comparable between older and younger patients.

Exercise, nutrition, and medication considerations in the light of the COVID pandemic, with specific focus on geriatric population: A literature review.

The pandemic of severe acute respiratory syndrome coronavirus 2 has spread across the world, causing causalities and inflicting chronic complications in those who survive the infection. Disruptions in the immune system and lowered physical levels caused by quarantine protocols are the major causes of chronic dysfunction and impaired life independency, especially in elderly patients. Multiple exercise suggestions and novel program delivery methods, including telerehabilitation/tele-exercise programs, home-gym strategies, and exergames, have emerged. Patients with underlying obesity, diabetes mellitus, malnutrition, or binge-eating problems are at a high risk of serious infection and sequela. Adequate education and coping strategies can lessen the potential infection complications and improve the quality of life. Acknowledging the possible benefits and risks of nonsteroidal anti-inflammatory drug usage in chronic pain patients, and the supplementation of vitamin D may also aid in treating post-infected patients.

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy

BackgroundTocilizumab, a humanized monoclonal antibody, targets IL-6 receptors blocking downstream pro-inflammatory effects of IL-6. In preliminary reports it was suggested to be beneficial in patients with severe COVID-19. MethodsIn this open-label prospective study we describe clinical characteristics and outcome of 51 patients hospitalized with confirmed and severe COVID-19 pneumonia treated with tocilizumab intravenously. All patients had elevated IL-6 plasma level (>40 pg/mL) and oxygen saturation <93% in ambient air. Clinical outcomes, oxygen support, laboratory data and adverse events were collected over a follow-up of 30 days. ResultsForty-five patients (88%) were on high-flow oxygen supplementation, six of whom with invasive ventilation. From baseline to day 7 after tocilizumab we observed a dramatic drop of body temperature and CRP value with a significant increase in lymphocyte count (p<0.001). Over a median follow-up time of 34 days from tocilizumab, 34 patients (67%) showed an improvement in their clinical severity class; 31 were discharged; 17 (33%) showed a worsening of their clinical status, of these 14 died (27%). The mortality rate was significantly associated with mechanical ventilation at baseline (83.3% vs 20% of patients on non-invasive oxygen support; p=0.0001). The most frequent side effects were an increase of hepatic enzymes (29%), thrombocytopenia (14%), and serious bacterial and fungal infections (27%). ConclusionTocilizumab exerts a rapidly beneficial effect on fever and inflammatory markers, although no significant impact on the clinical outcome can be inferred by our results. Critically ill patients seem to have a high risk of serious infections with this drug.

Antibody Dependent Enhancement of Infections after High Dose Chemotherapy

Background: High dose chemotherapy (HDT) burdens patients with a high risk of serious infections while neutropenic. The role of host antibodies as risk factors for infections is unclear. Our aim was to investigate if pre-HDT levels of IgG antibodies against terminal Galα3Gal (anti-αGal) predict infections. Anti-αGal is reported to be the most abundant antibody in human plasma and is able to recognize most sepsis-causing Gram-negative bacteria. The antibody exerts poor complement activation, which promotes pathogen survival by blocking access of more effective complement activators. This may be particularly problematic in neutropenic patients. Thus, we hypothesized that patients with high anti-αGal serum concentrations are particularly prone to suffer infections following HDT. Methods: We conducted a clinical cohort study on patients ≥16 years receiving HDT with autologous stem cell transplantation for myelomatosis (MM) or non-Hodgkin lymphoma (NHL) at Department of Hematology, Aarhus University Hospital, Denmark from 25 November 2009 through 26 June 2015. Of eligible patients (N=308), we excluded previous transplanted (N=14), those without a pre-HDT serum sample available for anti-αGal quantification (N=115), and recipients of plasma transfusion/IgG substitutions within 90 days before the pre-HDT serum sample and until end of follow-up (N=9). All included received prophylactic antimicrobial therapy (levofloxacin and fluconazol) and filgrastim. Serum anti-αGal was quantified using an in-house Time-resolved Immuno-Fluoremetric Assay. We ascertained infectious episodes within 30 days following the date of autologous stem cell re-infusion through review of all medical charts and data retrieval from the laboratory information systems, blinded for anti-αGal concentrations. Infectious episodes were defined as fever (≥38.5°C) or hypothermia (&lt;36°C) prompting antibiotic treatment and CRP &gt; 21 mg/L preceded by at least 24 hours without any of these. We used a Cox proportional hazards model to investigate the association between anti-αGal concentrations and risk of infection, with adjustment for total plasma IgG concentrations, ABO blood group, comorbidity, and underlying disease (MM or NHL) in the adjusted hazard ratios (HR). Optimum cutoff for dichotomizing was determined from ROC analysis applying Youden´s J statistic and groups were compared by Kaplan-Meier method. Results: We included 170 patients (MM, 55%; males, 58%; median age 62 years). Severe neutropenia was transient in all, with blood neutrophils increasing to above 500/µL on median day 11 (range 8-18). We identified one infectious episode in 103 patients (61%) and two episodes in six (3.5%) patients. The infectious episodes began during severe neutropenia in 92% of the patients. The infection types were fever of unknown origin (FUO) (72%), pneumonia (19%), catheter related (4.3%), typhlitis (1.7%), C. difficile colitis (1.7%), and hypothermia of unknown origin (0.87%). None died from infections. Pre-HDT serum was collected on median day -31 (range -142- -16). Anti-αGal was detectable in all but one sample, averaging 0.51 mg/dL (range: 0.016-12). Overall, anti-αGal concentrations predicted infectious episodes (all types), crude HR 1.2 (95% confidence interval (CI) 1.1-1.4), adjusted HR 1.1 (95% CI: 1.0-1.3). Using anti-αGal at 1.3 mg/dL as cut-off, we identified that patients with higher concentrations (N=41) experienced considerably increased risk of infectious episodes (crude estimates): all types, HR 1.7 (95% CI: 1.3-3.2); FUO, HR 2.0 (95%CI: 1.5-4.5); and pneumonia HR 2.1 (95%CI: 0.83-8.7). Discussion: We found that high anti-αGal serum concentrations predict an increased risk of infection after HDT. These findings support that anti-αGal may critically enhance pathogen-survival in the neutropenic host. Studies of other cohorts and mechanistic studies are required. Our findings may pave the way for future optimized risk stratification and therapeutic measures. Disclosures No relevant conflicts of interest to declare.

Risk of Infections and Cancer in Patients With Rheumatologic Diseases Receiving Interleukin Inhibitors

The safety profile of interleukin (IL) inhibitors is not well established. To assess the risk of serious infections, opportunistic infections, and cancer in patients with rheumatologic diseases treated with IL inhibitors. Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations; Ovid MEDLINE Daily; Ovid Embase; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus were searched (inception to November 30, 2018). Randomized, placebo-controlled trials that evaluated IL inhibitor therapies in rheumatic diseases and reported safety data were included in the analyses. This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Two investigators independently extracted study data and assessed risk of bias and certainty in the evidence. Fixed-effects meta-analysis was conducted to pool odds ratios (ORs) for serious infections, opportunistic infections, and cancers for IL inhibitors vs placebo. The outcomes of interest were the number of serious infections, opportunistic infections, and cancers in individuals receiving IL inhibitor therapies compared with placebo. In this meta-analysis, 74 studies comprising 29 214 patients (24 236 patients for serious infections, 9998 for opportunistic infections, and 21 065 for cancer [number of patients overlaps for each outcome]) were included. Patients receiving IL inhibitors had a higher risk of serious infections (OR, 1.97; 95% CI, 1.58-2.44; P < .001, I2 = 0%; high certainty), opportunistic infections (OR, 2.35; 95% CI, 1.09-5.05; P = .03, I2 = 0%; moderate certainty), and cancer (OR, 1.52; 95% CI, 1.05-2.19; P = .03, I2 = 11%; moderate certainty). The risk of serious infections, opportunistic infections, and cancer appears to be increased in patients with rheumatologic diseases who are treated with IL inhibitors compared with placebo.

688 Probability of Vedolizumab Response as Defined by Clinical Decision Support Tool Is Associated With Lower Risk of Serious Infection in Patients With Inflammatory Bowel Disease

INTRODUCTION: Disease activity is an independent predictor of infection in patients receiving biologics; non-response to a therapy might therefore present a higher risk of serious infection due to persistence of disease activity. We hypothesized that a clinical decision support tool (CDST) predicting lower treatment response may be predictive of a higher risk of infection. METHODS: Two validated CDSTs predicting vedolizumab (VDZ) response in ulcerative colitis (UC) and Crohn's disease (CD) were used on GEMINI phase 3 clinical trial data. After stratification by baseline variables into low, intermediate, or high probability of response to VDZ, time-to-event with Cox proportional hazard models was used to compare the risk of infection across groups and to identify independent predictors of infections among subgroups. RESULTS: 618 UC and 1023 CD patients were included. Those categorized as having low-intermediate probability of response (n = 479 UC, n = 814 CD) to VDZ were more likely to develop infectious complications while on therapy than those categorized as having high probability (n = 139 UC, n = 209 CD) response to VDZ (UC: hazard ratio [HR] 1.383, 95% confidence interval [CI] 1.024−1.868; CD: HR 1.458, 95% CI 1.124−1.893). Serious infections were observed in 1% of UC and 3% of CD patients in the high probability of response groups vs 2% of UC and 5% of CD patients in the low-intermediate groups. Among the low-intermediate probability of response UC group, independent predictors of developing infection were: baseline extraintestinal manifestations (no vs yes; HR 0.755, 95% CI 0.569−1.001); previous tumor necrosis factor antagonist exposure (no vs yes; HR 0.671, 95% CI 0.497−0.906); and baseline fecal calprotectin (log transformed; HR 1.135, 95% CI 1.016−1.268). Among the low-intermediate probability of response CD group, an independent predictor of developing infection was exposure to opioids during treatment (yes vs no; HR 1.829, 95% CI 1.469−2.277). CONCLUSION: This analysis confirms a pattern of inverse correlation between CDST-predicted efficacy and risk of infection. Data are consistent with the VDZ safety profile and suggest that infectious events seen were related to persistence of disease activity as opposed to drug-related mechanisms.

Predicting serious bacterial infection in febrile young infants utilizing body temperature.

Febrile young infants have a high risk of serious infection. Although measuring vital sign parameters can serve as a rapid and effective assessment in these patients, their predictive value for serious bacterial infection (SBI) has not been fully investigated. This retrospective observational study enrolled febrile (>38.0°C) infants aged <90days at the time of presentation. Data from the emergency room triage database at Tokyo Metropolitan Children's Medical Center for the period 1 November 2011-30 November 2013, were reviewed. Variables included patient age, gender, and vital sign data, including body temperature, pulse rate, oxygen saturation, definitive diagnosis, and disposition. Two hundred and sixty-nine patients were included, with a mean age of 55days, and 158 (58.7%) were male. Of the total, 43 patients had an SBI. On logistic regression, body temperature ≥38.5°C (OR, 2.80; 95%CI: 1.37-5.74) was a significant predictor of SBI. High-grade fever was found to be a significant predictor of SBI in febrile young infants.

Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

Evaluation of Romyelocel-L Myeloid Progenitor Cells to Decrease Infections in De Novo AML Patients Receiving High-Dose Ara-C-Based Induction Therapy

Incidence of Infectious Adverse Events in Patients With Rheumatoid Arthritis and Spondyloarthritis on Biologic Drugs-Data From the Brazilian Registry for Biologics Monitoring.

BackgroundThe safety profile of biologic drugs might present substantial regional differences. Since 2009, the Brazilian Society of Rheumatology has maintained BIOBADABRASIL (Brazilian Registry for Biologic Drugs), a registry for monitoring of biologic therapies in rheumatic diseases.ObjectivesThe aim of this study was to verify the incidence rate (IR) of serious infections in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients on biologic drugs.MethodsBIOBADABRASIL prospectively included patients with rheumatic diseases who started the first biologic drug or a synthetic disease-modifying antirheumatic drug as a parallel control group. This study focuses on serious infectious adverse events (SIAEs) in RA and SpA patients on biologic drugs compared with controls, from January 2009 to June 2015. Time of exposure was set from initiation of the drug to the date of last administration or censorship. Serious infectious adverse events IR was calculated per 1000 patient/years with 95% confidence interval (CI).ResultsA total of 1698 patients (RA, 1121; SpA, 577) were included, 7119 patient/years. Serious infectious adverse events were more common among patients on tumor necrosis factor inhibitors (TNFi's) than controls (adjusted IR ratio, 2.96 [95% CI, 2.01–4.36]; p < 0.001). Subsequent TNFi was associated with a higher SIAEs incidence when compared with first TNFI (adjusted IR ratio, 1.55 [95% CI, 1.15–2.08]; p = 0.004). Serious infectious adverse events were associated with age and corticosteroids intake. Serious infectious adverse events were more frequent in the respiratory tract in all subgroups.ConclusionsIn BIOBADABRASIL, biologic drugs, especially the subsequent TNFi, were associated with a higher risk of serious infections compared with synthetic DMARDs. Corticosteroid intake and age represented risk factors for SIAEs. Constant monitoring is required to follow the safety profile of drugs in the clinical setting of rheumatic conditions in Brazil.

Occurrence and Antibiotic Resistance of Enterobacteriaceae in Acute Leukemia Patients.

Acute leukemia (AL) is a heterogeneous group of malignant hematopoietic diseases and is divided into two basic types: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Patients with these diseases are highly immunosuppressed and therefore at a high risk of serious infections. This study aimed to perform active surveillance of enterobacteria, which cause these infections, and to determine their antibiotic resistance in patients with AL who were hospitalized at the Hemato-Oncology Center of University Hospital Olomouc. This study involved 49 patients with AL, of whom 37 had AML (16 women and 21 men) and 12 had ALL (6 women and 6 men). The mean age of the patients was 50.5 years. Samples of clinical material were obtained over 12 months (September 2015 to August 2016) and subjected to standard microbiological examinations. Bacterial strains were identified by MALDI-TOF MS, and their antibiotic susceptibility was established by microdilution method. A total of 292 samples were obtained from patients with AL. Some of these samples were excluded from analysis to prevent the inclusion of identical strains from the same patient. Consequently, 146 clinical samples obtained from the following nine types of clinical materials were analyzed - throat swabs (n = 47), stools (n = 40), urine (n = 33), hemocultures (n = 11), buccal swabs (n = 5), perianal swabs (n = 4), wound swabs (n = 3), sputum (n = 2), and puncture fluid (n = 1). The most prevalent enterobacteria was Escherichia coli (n = 42), followed by Klebsiella spp. (n = 46), specifically Klebsiella pneumoniae (n = 34) and Klebsiella oxytoca (n = 12), and Enterobacter cloacae (n = 19). The most of enterobacteria were highly resistant to many tested antibiotics. Antibiotic-resistant enterobacteria colonize patients with hemato-oncological diseases and can cause serious infections. These antibiotic-resistant microorganisms are a serious and frequent problem. These findings together with the high level of immunosuppression mean that patients with hemato-oncological diseases are at a high risk of developing serious infections and consequently active surveillance is crucial.

Covering the Cover

Covering the Cover