Incidence Of Severe Infections Research Articles

Incidence of severe infection in patients with rheumatoid arthritis taking biologic agents: a systematic review.

The objective of this review was to estimate the population-based incidence and determine the types of severe infection and deaths experienced by patients with rheumatoid arthritis taking biologic agents. Since the late 1990s, various biologic and synthetic drugs have been developed to treat rheumatoid arthritis. In recent years, the incidence of severe infection in patients with rheumatoid arthritis in Western nations has been determined by observational studies; however, no systematic review has been conducted on this topic. The following inclusion criteria were considered: i) observational studies on patients with rheumatoid arthritis treated with biologic agents; ii) studies reporting the number of severe infections requiring hospitalization for treatment; iii) studies reporting person-years of observation data; and iv) studies based on rheumatoid arthritis registries, medical records from rheumatology centers, or insurance claim databases. PubMed, CINAHL, Embase, and Web of Science were searched to identify published studies. The reference lists of all studies selected for critical appraisal were screened for additional studies. Unpublished studies were searched on MedNar and OpenGrey databases. All the searches were updated on December 6, 2021. After removing the duplicates, 2 independent reviewers screened titles and abstracts against the inclusion criteria and then assessed full texts against the criteria. Two reviewers independently appraised the study and outcome levels for methodological quality using the critical appraisal instrument for cohort studies from JBI. Two reviewers extracted the relevant information related to severe infection and drugs. Fifty-two studies from 21 countries reported severe infection rates associated with using 8 biologic agents, plus nonbiologic disease-modifying antirheumatic drugs. In total, 18,428 infections with 395,065 person-years of biologic drug exposure were included in the analysis. Thirty-five studies included infections in outpatients receiving intravenous antibiotic therapy. Fifteen studies reported the first episode of infection, and the remaining studies did not specify either the first or all of the episodes of infection. Inclusion of viral infection and/or opportunistic infection varied among studies. Fifteen studies reported the site of infection; respiratory, skin/soft tissue, urinary tract, and sepsis/bacteremia were commonly reported. Ten studies reported the case fatality rates, ranging from 2.5% to 22.2%. Meta-analysis was conducted for 8 biologic agents and conventional disease-modifying antirheumatic drugs. The infection rate varied from 0.9 to 18.1/100 person-years. The meta-analysis revealed an infection rate of 5.0/100 person-years (95% CI 3.8-6.7) among patients receiving tumor necrosis factor inhibitors (heterogeneity 98.2%). The meta-analysis for the other 3 biologic agents revealed a point estimate of 5.5 to 8.7/100 person-years with high heterogeneity. Sensitivity analysis indicated that registry-based studies were less likely to have very low or very high infection rates compared with other data sources. The definition of infection, the patient composition of the cohorts, and the type of databases appeared to be the primary sources of clinical and methodological heterogeneity. Due to high statistical heterogeneity, the meta-analysis was not suited to estimating a summary measure of the infection rate. Developing standardized data collection is necessary to compare infection rates across studies. PROSPERO CRD42020175137.

Abstracts for a wider audience: promoting linguistic diversity in JBI Evidence Synthesis.

Abstracts for a wider audience: promoting linguistic diversity in JBI Evidence Synthesis.

Association between hypogammaglobulinaemia and severe infections during induction therapy in ANCA-associated vasculitis: from J-CANVAS study.

To investigate the association between decreased serum IgG levels caused by remission-induction immunosuppressive therapy of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the development of severe infections. We conducted a retrospective cohort study of patients with new-onset or severe relapsing AAV enrolled in the J-CANVAS registry, which was established at 24 referral sites in Japan. The minimum serum IgG levels up to 24 weeks and the incidence of severe infection up to 48 weeks after treatment initiation were evaluated. After multiple imputations for all explanatory variables, we performed the multivariate analysis using a Fine-Gray model to assess the association between low IgG (the minimum IgG levels <500 mg/dl) and severe infections. In addition, the association was expressed as a restricted cubic spline (RCS) and analysed by treatment subgroups. Of 657 included patients (microscopic polyangiitis, 392; granulomatosis with polyangiitis, 139; eosinophilic granulomatosis with polyangiitis, 126), 111 (16.9%) developed severe infections. The minimum serum IgG levels were measured in 510 patients, of whom 77 (15.1%) had low IgG. After multiple imputations, the confounder-adjusted hazard ratio of low IgG for the incidence of severe infections was 1.75 (95% confidence interval: 1.03-3.00). The RCS revealed a U-shaped association between serum IgG levels and the incidence of severe infection with serum IgG 946 mg/dl as the lowest point. Subgroup analysis showed no obvious heterogeneity between treatment regimens. Regardless of treatment regimens, low IgG after remission-induction treatment was associated with the development of severe infections up to 48 weeks after treatment initiation.

Compounded sulfamethoxazole improved the prognosis of dermatomyositis patients positive with anti-melanoma differentiation-associated gene 5.

Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups-coSMZ and non-coSMZ-based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Compared with the non-coSMZ group (n = 93), the coSMZ group (n = 121) had lower mortality (18.8% vs 51.1%; P < 0.001) and a lower incidence of PJP (6.8% vs 15.2%; P = 0.040) and fatal infection (16.1% vs 3.3%; P = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102-0.878), P = 0.028]. Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP.

Quality indicators in burn care: An international burn care professionals survey to define them

IntroductionQuality indicators (QIs) are tools for improving and maintaining the standard of care. Although burn injuries are a major global health threat, requiring standardized management, there is a lack of worldwide accepted quality indicators for burn care. This study aims to identify the best burn care-specific QIs as perceived by worldwide burn practitioners. MethodsThe ISBI Burn Care Committee developed a survey to analyze which burn care- specific QIs were relevant to international burn care professionals. The questionnaire was based on the three dimensions of the Donabedian model (i.e., Structure, Process, and Outcome) to evaluate the quality of care. The study was conducted from April to September 2021 and analyzed and reported following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). ResultsAccording to the 124 worldwide respondents, the most relevant QIs were: access to intensive care, burn surgeons, and dedicated burn care nurses (Structure category), 24-hours access to burn services, local protocols based on documented guidelines (Process category), and in-hospital mortality and incidence of severe infections (Outcome category). ConclusionsSpecific QIs related to structures, clinical processes, and outcomes are needed to monitor the treatment of burn patients globally, assess the efficiency of the provided treatment, and harmonize the worldwide standard of burn care.

A comparison of C+SCAV and SEAM conditioning regimens in efficacy and safety in autologous hematopoietic stem cell transplantation for non-Hodgkin's lymphoma patients

Objective: This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin's lymphoma (NHL) . Methods: A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively. Results: ① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups (P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group (P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM (P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group (P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) (P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) (P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) (P=0.389) , respectively. Conclusion: C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.

MO874: Incidence of Severe Infections in Home Haemodialysis and Peritoneal Dialysis Patients

Abstract BACKGROUND Dialysis patients have a more than ten-fold risk of dying from infections compared with general population. In earlier studies, the risk of infections was similar in peritoneal dialysis (PD) and haemodialysis (HD), but comparison to home HD has not been performed. Our aim was to study the incidence of severe infections after start of home HD as compared with continuous ambulatory PD (CAPD) and automated PD (APD). METHODS We included all 536 adult patients, who were on home dialysis at day 90 from start of kidney replacement therapy (KRT) between 2004 and 2017 in Helsinki healthcare district. Severe infections were identified from patients’ laboratory data as a plasma C-reactive protein over 100 mg/L and confirmed from the patient data system. The cumulative incidence of the first severe infection was estimated considering death as a competing risk event. Hazard ratios of first severe infection were assessed using Cox regression with propensity score adjustment. Incidence rate (IR) and ratios (IRR) of all severe infection episodes were calculated. RESULTS The probability of getting a severe infection during the first year of dialysis was 35% for CAPD, 25% for APD and 11% for home HD patients. During a 5-year follow-up, the hazard ratio of severe infection was 2.8 [95% confidence interval (95% CI) 1.6–4.8] for CAPD and 2.2 (95% CI 1.4–3.5) for APD in comparison to home HD with adjustment for propensity scores. IR of infections/100 patient-years was 54 for CAPD, 37 for APD and 20 for home HD patients. The IR of peritonitis was 37 for CAPD and 25 for APD patients. When infection episodes caused by peritonitis were excluded, the IR of severe infections was not higher among PD than home HD patients. CONCLUSION The risk of severe infection was considerably lower among home HD than PD patients. This difference was mainly explained by the peritonitis episodes among the PD patients.

Extracorporeal Photopheresis With Low-Dose Immunosuppression in High-Risk Heart Transplant Patients-A Pilot Study.

In severely ill patients undergoing urgent heart transplant (HTX), immunosuppression carries high risks of infection, malignancy, and death. Low-dose immunosuppressive protocols have higher rejection rates. We combined extracorporeal photopheresis (ECP), an established therapy for acute rejection, with reduced-intensity immunosuppression. Twenty-eight high-risk patients (13 with high risk of infection due to infection at the time of transplant, 7 bridging to transplant via extracorporeal membrane oxygenation, 8 with high risk of malignancy) were treated, without induction therapy. Prophylactic ECP for 6 months (24 procedures) was initiated immediately postoperatively. Immunosuppression consisted of low-dose tacrolimus (8–10 ng/ml, months 1–6; 5–8 ng/ml, >6 months) with delayed start; mycophenolate mofetil (MMF); and low maintenance steroid with delayed start (POD 7) and tapering in the first year. One-year survival was 88.5%. Three patients died from infection (POD 12, 51, 351), and one from recurrence of cancer (POD 400). Incidence of severe infection was 17.9% (n = 5, respiratory tract). Within the first year, antibody-mediated rejection was detected in one patient (3.6%) and acute cellular rejection in four (14.3%). ECP with reduced-intensity immunosuppression is safe and effective in avoiding allograft rejection in HTX recipients with risk of severe infection or cancer recurrence.

Standard-Intensity Induction and Intermediate/High-Dose Cytarabine Consolidation Can Improve Survival for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia: A Retrospective Cohort Study.

BackgroundThere is great uncertainty in the treatment of elderly patients with acute myeloid leukemia (AML), which leads to great challenges in treatment decision. The aim of this study is to find more suitable induction therapy and consolidation therapy for elderly AML patients.MethodsA total of 149 consecutive newly diagnosed elderly AML patients (aged ≥60 years) who received induction chemotherapy in our medical center from January 2015 to December 2019 were retrospectively analyzed.ResultsAfter the first induction treatment, the complete remission/or complete remission with incomplete hematologic recovery (CR/CRi) rates in the standard-intensity chemotherapy group was significantly higher than that in the low-intensity chemotherapy group (58.2% vs 32.9%, p = 0.003). Compared with the low-intensity chemotherapy, the incidence of severe infection in the standard-intensity chemotherapy was significantly increased (p < 0.001), but the early mortality was comparable. One hundred and seven patients received minimal residual disease (MRD) examination after the first induction treatment; and MRD was negative accounting for 51.9% in the standard-intensity chemotherapy group, while only 32.7% in the low-intensity group (p = 0.05). The 2-year-overall survival (OS) of patients in standard-intensity induction chemotherapy group (37.2%) was slightly higher than that in low-intensity induction chemotherapy group (23.4%) (p = 0.075). Eighty-one CR/CRi patients received intermediate or high dose cytarabine (n = 35) or sequential chemotherapy regimens (n = 46) as consolidation treatment. The 2-year OS and event-free survival (EFS) of patients in the intermediate or high-dose cytarabine group were significantly higher than those in the sequential chemotherapy regimens group (73.0% vs 38.5%, p = 0.002; 54.8% vs 35.0%, p = 0.035).ConclusionOur results showed that standard-intensity induction chemotherapy can significantly improve the CR rate for elderly AML patients, and does not increase the early mortality; consolidation therapy with intermediate or high-dose cytarabine can significantly improve EFS and OS for elderly AML patients achieved CR.

Corticosteroids Use and Incidence of Severe Infections in People Living with HIV Compared to a Matched Population

Background:People living with HIV (PLWH) have been shown to have an increased risk of autoimmune diseases. Corticosteroids are the cornerstone of autoimmune diseases treatment, but their use is associated with an increased risk of infections. It is unclear how HIV status affects the risk of infection associated with corticosteroids use.Methods:We conducted a retrospective cohort study from 1991 to 2011, using a medico-administrative database from Quebec. Medical billing codes were used to identify PLWH, and we matched them on age, sex, and index date with up to 4 HIV-negative controls. The exposure of interest was the use of corticosteroids, defined as a systemic corticosteroid dispensation lasting at least 20 days. The outcome of interest was hospitalization for severe infection. Crude and adjusted incidence rates ratios of infection were obtained using a random effect Poisson model, and results were stratified by HIV status.Results:In total, 4798 PLWH were matched to 17 644 HIV-negative controls, among which 1083 (22.6%) PLWH and 1854 (10.5%) HIV-negative controls received at least one course of corticosteroid. The mean duration of corticosteroids use was 4 ± 4.4 months in PLWH and 1.6 ± 5.5 months in HIV-negative controls. The incidence rate ratio (IRR) for infections associated with corticosteroids use was 2.49[1.71–3.60] in PLWH and 1.32[0.71–2.47] in HIV-negative controls (P value for interaction 0.18). The most frequent infections were pulmonary infections (50.4%), followed by urinary tract infections (26%) and opportunistic infections (10.5%).Conclusion:Although our interaction term did not reach significance, the increased risk of infection associated with corticosteroids use was more pronounced in PLWH. However, further research with contemporary data is warranted to confirm if the risk associated with corticosteroids use remains high in PLWH with well-controlled HIV infection.

Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004-12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introducedafter 28days of SOC in the event of failure (G1a, n=19) or PP withdrawal (G1b, n=12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p=.08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.

Clinical Characteristics and Outcome of Coronavirus Disease 2019 Infection in Patients with Solid Organ Transplants: A Systematic Review and Meta-Analysis

Importance: Although many studies have reported cases of COVID-19 infection in transplant recipients, most of them only involve a small number of patients and narrow geographic areas.Objective: This study aims to investigate the clinical characteristics, morbidity, severity, and mortality of COVID-19 infection among solid organ transplant (SOT) recipients by meta-analysis.Data Sources: We performed a literature search using the databases PubMed, Web of Science, and Google Scholar as of November 26, 2020.Study Selection Pooled incidence proportion (i.e., cumulative incidence) and 95% confidence intervals (CI) were determined to estimate morbidity, severity, and mortality of COVID-19 in SOT recipients as well as clinical symptoms.Data Extraction and Synthesis: Cochrane chi-square test statistic, Q statistic, and Higgin’s I2 statistic were used to evaluate heterogeneity among the studies. Publication bias and sensitivity of the included studies were also tested.Results: Forty-eight studies were included in the meta-analysis. The morbidity rate of COVID-19 in SOT recipients was 2·10% (95% confidence intervals [CI] 1·35-3·01), incidence of severe infection was 22·46% (95% CI 15·74-29·90), and mortality rate was 17·38% (95% CI, 13·72-21·34). In the transplanted organ analysis, the proportion of patients with severe infection was highest in the recipients of two or more transplants (48·85% [95% CI 11·88-86·38]). Further, the mortality rate was highest in lung transplant recipients (25·12% [95% CI 16·94-34·00]). The most common symptoms of COVID-19 in SOT recipients were fever, cough, and respiratory symptoms, which were reported in 73·39%, 58·90%, and 45·77% of patients, respectively. Conclusion and relevance: The SOT was a significant risk factor for worse COVID-19 outcomes, although the morbidity of COVID-19 in SOT recipients was not markedly higher than that in the general population.Funding Statement: The authors received no financial support for the research, authorship, and/or publication of this article.Declaration of Interests: The authors have no conflicts of interest to declare.

A prospective cohort study of rituximab in the treatment of refractory nephrotic syndrome

ObjectiveTo explore the efficacy and safety of rituximab (RTX) in the treatment of autoimmune nephropathy manifested as refractory nephrotic syndrome (RNS).MethodsA single-center prospective cohort study was conducted on RNS patients treated with RTX between March 2017 and December 2019. The subjects were divided into the primary nephropathy (PN) group and the secondary nephropathy (SN) group. Based on the estimated glomerular filtration rate (eGFR) before RTX treatment, the SN group was then divided into the SN-1 group (eGFR ≥ 30 ml/min) and the SN-2 group (eGFR < 30 ml/min). Biochemical parameters and clinical data were recorded during follow-up.ResultsFifty-four patients were followed up for at least 6 months. The overall remission rates were 65%, 66.7%, 27.3% in the PN, SN-1, and SN-2 groups, respectively (P = 0.022). Kaplan–Meier analysis showed a significant difference of the renal survival among the three subgroups (P < 0.001). Multivariate Cox regression analysis showed that eGFR value before treatment was an independent predictor (HR 0.919, 95%CI 0.863–0.979) for renal survival. In terms of adverse events, infection accounted for 56.6%. The incidence of severe infection was 10%, 25% and 50% in PN group, SN-1 group and SN-2 group, respectively.ConclusionsRTX may be a promising option in RNS patients with eGFR ≥ 30 ml/min/1.73m2. However, it has little effect on prognosis in patients with secondary RNS with eGFR < 30 ml/min/1.73m2, but with a high risk of severe infection.

P203 Incidence, characteristics and determinants of severe infections in patients with anti-neutrophil cytoplasm antibody-associated vasculitis receiving rituximab therapy: a single centre study

Abstract Background/Aims The efficacy of rituximab in managing anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is well-established; however its associated complications, including risk of developing serious infections, are less well characterised. Identifying infection risk factors may help to improve care of patients with AAV receiving rituximab. We characterised severe infections in a cohort of patients over a three-year period and identified factors affecting their risk of developing severe infections. Methods Electronic patient records were interrogated over a retrospective period (August 2016-August 2019) to compile baseline data and episodes of severe infection. Differences between groups were determined using appropriate parametric or non-parametric methods. Risk factors for severe infections were identified through multivariate binomial logistic regression analysis. Variables with an event count of ≥ 5 and a p-value ≤0.1 at univariate level were entered into the final multivariate analysis, where p ≤ 0.05 was taken as significant. Results Fifty patients were included. 24 (48%) were male, and 26 (52%) female. Average age was 60 years (range 25-90). 36 (72%) had GPA, 2 (4%) MPA, 1 (2%) EGPA, and 11 (22%) had overlap or undefined AAV. 14 (28%) patients developed at least one severe infection (≥grade 3, CTCAE criteria), giving an incidence of 15.4 severe infections per 100 person-years. The 18 severe infection events included 10 (56%) respiratory tract, 5 (28%) sepsis/neutropenic sepsis, 1 (6%) cellulitis, 1 (6%) complicated UTI and 1 (6%) recurrent wound infection. Patients who developed severe infections had lower immunoglobulin levels (IgG&amp;lt;6g/L, 36% vs 6%, p = 0.009), concomitant COPD (21% vs 3%, p = 0.029), and lower rates of concomitant co-trimoxazole use (7% vs 44%, p = 0.012) compared to patients not developing severe infections. Regression analysis of demographic, baseline blood markers and concomitant therapy data was performed to identify risk factors for developing severe infections (Table.1). Hypogammaglobulinaemia increased risk of infection (OR = 8.782, 95%CI=1.194-64.605, p = 0.033), while co-trimoxazole decreased risk of infection (OR = 0.096, 95%CI=0.009-0.996, p = 0.050). P203 Table 1:Univariate analysisMultivariate analysisVariablesOR95% CIP valueOR95% CIP valueAge (years)1.0320.994-1.0720.105Sex (male)0.3200.084-1.2130.0940.2860.057-1.4350.128Creatinine1.0050.987-1.0240.577eGFR0.9750.945-1.0060.109CRP1.0010.989-1.0120.899ESR1.0030.960-1.0460.908Neutrophils0.9730.789-1.2010.802WBC0.9590.780-1.1800.694Lymphocytes0.8700.420-1.8050.709CD190.4780.000-2000.9670.862CD19%0.9870.906-1.0750.767CD30.3140.055-1.7750.190CD3%0.9960.941-1.0550.902CD40.3920.034-4.4870.451CD4%1.0110.959-1.0660.675CD80.0530.001-4.7440.200CD8%0.9850.914-1.0610.689IgG0.8900.749-1.0570.185Hypogammaglobulinemic?8.6111.423-52.0910.0198.7821.194-64.6050.033IgM0.8360.350-1.9970.686IgA1.0890.787-1.5070.607BMI0.9460.858-1.0430.262COPD*9.5450.899-101.3380.061DM0.8330.147-4.7230.837Hypertension0.4330.082-2.2910.325CV disease0.000-0.999AKI0.4580.088-2.3780.353Latent TB0.3710.022-6.3830.495DI2.6920.157-46.2640.495Hypothyroidism0.000-1.000RA5.8330.484-70.2440.165OP2.6920.157-46.2640.495OA0.000-1.000SLE0.000-1.000AIH0.000-1.000CKD0.000-1.000Co-trimoxazole use0.0960.011-0.8150.0320.0960.009-0.9960.050Cumulative dose of RTX0.6690.392-1.1410.140Did patient have prior RTX before Aug 2016?0.6940.194-2.4870.575Yearly influenza vaccine between 2016-2019 (patients for whom vaccine records exist on EPR)1.3850.188-16.2770.796Average length of follow-up (days)1.0010.999-1.0030.360Prednisolone cumulative dose1.0001.000-1.0000.843Prednisolone average dose0.9920.991-1.0800.852MTX cumulative dose1.0000.999-1.0010.701MTX average dose1.0200.696-1.4960.918HCQ cumulative dose1.0001.000-1.0000.331HCQ average dose0.9850.964-1.0060.162LFN cumulative dose1.0001.000-1.0000.855LFN average dose0.8510.605-1.1990.357MMF cumulative dose1.0010.999-1.0020.263MMF average dose3.9960.402-39.7260.237AZT cumulative dose1.0001.000-1.0000.372AZT average dose0.9440.878-1.0140.116*too few events for progression to multivariate analysis. Conclusion The incidence of severe infections in patients with AAV receiving rituximab is significant. Our results support the monitoring of IgG levels to identify patients who may be more susceptible to infection, as well as the prescription of prophylactic co-trimoxazole to reduce overall severe infection risk. Disclosure F. Dernie: None. N. Ahmad: None. R. Luqmani: None. J. David: None.

Severe infection risk in patients treated with biologics for rheumatoid arthritis: a systematic review protocol.

The objective of this review is to estimate the population-based incidence and to determine the types of severe infection experienced by patients with rheumatoid arthritis who are taking biological agents. Since the late 1990s, a variety of biological and synthetic drugs have been developed to treat rheumatoid arthritis. In recent years, the incidence of severe infection in patients with rheumatoid arthritis in Western nations has been reported by observational studies; however, no systematic review has been conducted on this topic. The following criteria will be considered for inclusion: i) observational studies on patients with rheumatoid arthritis who are taking biological agents; ii) studies reporting the number of severe infections requiring hospitalization for treatment; and iii) studies with person-years of observational data. MEDLINE, CINAHL, Embase, and Web of Science will be searched to identify published studies. The reference lists of all studies that are selected for critical appraisal will be screened for additional studies. The search for unpublished studies will include MedNar and OpenGrey. Only studies published in English from 1999 to the present will be included. Screening of studies, assessment of methodological quality, and data extraction will be performed by two independent reviewers. If possible, studies will be pooled in statistical meta-analysis. PROSPERO CRD42020175137.

Association between body mass index and severe infection in older adults with microscopic polyangiitis: a retrospective cohort in Japan

BackgroundAlthough previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV.MethodsThis single-center retrospective cohort study included 93 consecutive older adults with microscopic polyangiitis (MPA) treated at the Aichi Medical University Hospital in Japan between 2004 and 2018. The relationships between BMI at diagnosis and subsequent first severe infection were assessed using multivariate Cox proportional hazards models. The cumulative probability of the development of the first severe infection was calculated using the Kaplan-Meier method and the log-rank test. The level of statistical significance was set at P < 0.05.ResultsDuring the median follow-up period of 19 (6–53) months, 29 (31.2%) patients developed at least one severe infection. Older age (adjusted hazard ratio [HR] = 2.02, 95% confidence interval [CI]: 1.14–3.52, per 10 years; P = 0.016), low BMI (< 18.5 kg/m2 compared with normal BMI [18.5–23.0 kg/m2], adjusted HR = 2.63, 95% CI: 1.11–6.19; P = 0.027), and use of methylprednisolone pulse therapy (adjusted HR = 2.48, 95% CI: 1.07–5.76; P = 0.034) were found to be significant predictors of severe infection.ConclusionsLow BMI was associated with a higher risk of severe infection in older adults with MPA, suggesting that careful management may be required to prevent this complication in this vulnerable group. Further studies are needed to elucidate the optimal treatment strategy for these patients.

Long‐term efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 5‐year extension of a phase 3 study (reSURFACE 1)

The three part, double‐blind, randomized, controlled reSURFACE 1 trial and extension study (NCT01722331) evaluated efficacy and safety of tildrakizumab in adults with moderate to severe plaque psoriasis. Patients with ≥50% improvement from baseline in Psoriasis Area and Severity Index (PASI 50) following treatment with tildrakizumab 100 mg (TIL100) or 200 mg (TIL200) could enter the optional long‐term extension study and continue treatment at the same dose for an additional 192 weeks. This subgroup analysis assessed the long‐term efficacy and safety of tildrakizumab treatment for Japanese patients enrolled in reSURFACE 1 for up to 5 years of treatment. The primary efficacy outcomes were the proportions of patients who maintained PASI 75 and Physician Global Assessment (PGA) clear or minimal with ≥2‐grade reduction from baseline (PGA 0/1) from base study week 64 to extension week 192. Secondary outcomes were the proportion of patients who maintained PASI 90/100 from base study week 64 to extension week 192. Adverse events (AEs) were monitored throughout the study and for up to 20 weeks after the last study visit. Of the 120 Japanese patients who entered the reSURFACE 1 extension study, 43 (79.6%) patients receiving tildrakizumab 100 mg and 58 (87.9%) patients receiving tildrakizumab 200 mg completed the extension study. Of all Japanese patients with PASI 75/90/100 and PGA 0/1 at week 64, 85%/88% receiving TIL100/TIL200 maintained PASI 75, 70%/96% maintained PASI 90, 63%/67% maintained PASI 100, and 68%/72% maintained PGA 0/1 at extension week 192. AEs led to discontinuation in 1.7 patients per 100 patient‐years (P100PY) receiving tildrakizumab 100 mg and 0.8 P100PY receiving tildrakizumab 200 mg. Incidences of severe infections, malignancies, confirmed major adverse cardiac events, and hypersensitivity reactions were low in both treatment groups. Through 5 years of treatment, tildrakizumab maintained efficacy and was well tolerated with low rates of AEs of special interest.

Multisystem Inflammatory Syndrome in Children (MIS-C)

The coronavirus disease 2019 pandemic has been continuously spreading throughout the world. As of July 15, 2021, there have been more than 188 million confirmed cases and more than 4.06 million deaths. Although the incidence of severe infections is relatively low in children and adolescents compared to adults, a complication called multisystem inflammatory syndrome in children (MIS-C) may occur in some cases at approximately 2–6 weeks after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MIS-C can be seen in patients of various ages, from young infants to adolescents, and may present with diverse clinical manifestations. While fever present in a great majority of patients, symptoms suggesting the involvement of the digestive or nervous system and the skin and mucous membranes (Kawasaki disease-like symptoms) also appear in many cases. Cardiac involvement may also be observed, including left ventricular dysfunction, myocarditis, coronary artery dilatation, and coronary aneurysm. In some cases, hypotension or shock can occur, and mechanical ventilation or treatment in the intensive care unit may be necessary. Fortunately, recovery is generally reported after appropriate treatment. MIS-C is a rare but important complication of SARS-CoV-2 infection in children and adolescents. As such, it is important to recognize the clinical symptoms and provide appropriate treatment at an early stage. In this review, the epidemiology, clinical symptoms, suggested pathophysiology, diagnostic approach, and treatment of MIS-C will be discussed. © 2021 The Korean Society of Pediatric Infectious Diseases.

Impact of Preexisting Inflammatory Bowel Disease on the Outcome of Liver Transplantation for Primary Sclerosing Cholangitis.

Approximately 80% of patients with primary sclerosing cholangitis (PSC) also have inflammatory bowel disease (IBD), and its effect on the outcomes of liver transplantation (LT) for PSC is unclear. We retrospectively collected data from adults who underwent LT for PSC from 1989 to January 2018 in 4 French LT centers. We compared the rates of patient and graft survivals and of complications after LT. Among 87 patients, 52 (60%) had preexisting IBD. Excluding those who died within the first 3months, the 10-year patient survival and graft survival rates were 92.6% (95% confidence interval [CI], 84.3%-100%) and 77.1% (53.8%-85.3%), respectively, in the PSC with IBD (PSC-IBD) group and 97.1% (91.4%-100%; P=0.44) and 83.2% (69.6%-96.9%; P=0.43) in the isolated PSC group, respectively. Exposure to azathioprine after LT was significantly associated with mortality (odds ratio [OR], 15.55; 1.31-184.0; P=0.03), whereas exposure to mycophenolate mofetil was associated with improved survival (OR, 0.17; 95% CI, 0.04-0.82; P=0.03), possibly an era effect. The rate of recurrent PSC was 21% in the PSC-IBD group and 11% in the isolated PSC group (P=0.24). Severe infections occurred in 125 per 1000 person-years in both groups. Exposure to mycophenolate mofetil was associated with a lower risk of infection (OR, 0.26; 95% CI, 0.08-0.85; P=0.03). The presence of IBD was associated with cytomegalovirus (CMV) infection (OR, 3.24; 95% CI, 1.05-9.98; P=0.04). IBD prior to LT for PSC may not affect patient or transplant survival but may increase the risk of CMV infection.

Severe infections in patients with anti-neutrophil cytoplasmic antibody-associated vasculitides receiving rituximab: A meta-analysis.

The efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known. The purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX. PubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I2>50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression. The included studies encompassed 1434 patients with a median age of 51.9years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I2=90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I2=76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I2=58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I2=0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I2=27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100mg, p<.0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p=.03). Prevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.