Higher Rate Of Serious Infections Research Articles

Outcomes after kidney transplant alone in patients with cirrhosis-A case-control study.

Guidelines recommend kidney transplant alone (KTA) in compensated cirrhosis based on a few small studies, but this is not widely performed despite its potential benefit to patients and the organ supply. Our aim was to determine the outcomes of KTA in patients with compensated cirrhosis. From 1/2012 to 12/2021, outcomes in KTA recipients with compensated cirrhosis were retrospectively compared to patients with chronic liver disease (CLD) but no cirrhosis. Patients with compensated cirrhosis were also compared to a matched cohort (based on age, time on hemodialysis, sex, and ethnicity) of KTA recipients without CLD. The outcomes included patient survival, allograft failure, allograft rejection, serious infection, liver decompensation, and length of stay (LOS). Over 9 years, 1562 KTAs were performed, with 150 (9.6%) patients having CLD mostly due to chronic hepatitis C, and a median follow-up of 3.5 years. 32/150 (21%) had compensated cirrhosis at the time of KTA with a mean MELD-Na of 22 (1.5). Matched controls (n=189) were identified. We found no differences in patient survival (p=.07), allograft failure (p=.6), allograft rejection (p=.43), rates of serious infection (p=.31), as well as LOS (p=.61) among patients with compensated cirrhosis compared to patients with CLD but no cirrhosis, but with higher rates of liver decompensation (p=.004). Similarly, compared to patients without CLD, patients with cirrhosis had similar rates of patient survival (p=.20), allograft failure (p=.27), allograft rejection (p=.62) and LOS (p=.19) but with higher rates of serious infections (p=.001). Our study supports the safety and efficacy of KTA in patients with compensated cirrhosis.

Serious infections in patients with relapsing and progressive forms of multiple sclerosis: A German claims data study

BackgroundPeople with multiple sclerosis (pwMS) have a higher risk of serious infection (i.e., infection-related hospitalizations) than people without MS. Few studies have explored the risk of serious infections by MS phenotype in a real-world setting. This retrospective study compared the incidence of serious infections among people with relapse remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). MethodsAdult pwMS were selected from a German claims database, based on one inpatient or two outpatient diagnoses of MS (ICD-10 G35) by a neurologist from 01/01/2016 to 12/31/2018. Three cohorts (RRMS, PPMS, SPMS) were identified based on codes for MS subtypes included in the German Modification of the ICD-10 system. A fourth cohort of unspecified MS patients combined those with conflicting MS subtype diagnoses and multiple unspecified codes for MS. Serious infections were defined as hospitalizations for which infections were selected as the primary inpatient diagnosis. Infections were identified from a basket of ICD-10 codes distributed across 11 main categories, according to possible pathogen (e.g., other bacterial diseases [A30-A49]) or anatomical location (e.g., urinary tract infection [N39.0]). Multiple infections were counted if an interval of at least 60 days was recorded between episodes. Serious infections were counted from index (i.e., first recorded MS code) until the end of the study period or death. Incidence rates (IRs) were reported per 100 patient years (PY). ResultsA total of 4,250 pwMS (RRMS: 2,307, PPMS: 282, SPMS: 558, unspecified MS: 1,135) were included; 32 patients progressed from RRMS to SPMS during the follow-up period. Mean (SD) age at baseline was 46.6 (13.6), 61.9 (12.4), and 62.5 (11.8) years in patients with RRMS, PPMS, and SPMS, respectively. Most pwMS were female (RRMS 74.8%, PPMS 62.1%, SPMS 67.4%). Progressive pwMS were more likely to have at least 1 comorbidity (PPMS 87.2%, SPMS 87.5%) compared to those with relapsing MS (61.9%). Most RRMS patients received disease-modifying therapy during follow-up (82.1%), while less than half of progressive MS patients did (PPMS 23.8%, SPMS 31.4%). Over a mean (SD) follow-up period of 3.5 (0.8) years, the IR of serious infections per 100 PY was higher in progressive MS cohorts (PPMS 13.5 [11.3–16.1], SPMS 13.6 [12.0–15.3]) than in the RRMS group (3.4 [3.0–3.7]). Yearly IRs remained stable over time in each cohort. Where anatomical location was specified, respiratory (2.0 per 100 PY) and genitourinary (1.9 per 100 PY) infections were most common. Across all subtypes, higher rates of serious infections were observed in men and older patients. ConclusionProgressive MS, older age and male sex are associated with an increased risk of serious infections. Overall, respiratory and genitourinary infections were the most commonly reported serious infections.

Pelvic Actinomycosis. Autposy Finding

Background: Actinomycosis is a suppurative and granulomatous chronic infectious disease due to a gram positive, non-spore-forming, anaerobic bacteria, non-acid-alcohol resistant bacteria The organisms are indigenous in the oral cavity, pharynx, gastrointestinal tract, and genital tracts. There are at least 6 species that can affect the human, Actinomyces israelii is the most frequent. Methods & Materials: Autopsy is performed for alleged medical non-compliance to a 41-year-old woman with Paranoid Schizophrenia postpartum in treatment at the admission to the hospital she had normal vital parameters and standard physical examination, indirect anamnesis to parents reporting a different behavior in the last days. At necropsy, enlarged lungs are seen, with a yellowish, thick secretion. Abdomen hepatomegaly. Pelvic: left psoas with multiple abscesses. Is evidenced hypogastric plastron, involving uterus, small intestine, large intestine and bladder. To cut thick purulent brown material. Fallopian tubes and ovaries were not identified. Intrauterine contraceptive device is present. Pathologic diagnosis was: abscessed endometritis secondary to Actinomyces israelii with extension to cervix, appendages and pelvic organs with adherent plastron. Psoas abscesses with venous thrombosis. Pericarditis and lymphoplasmacytic myocarditis. Bronchopneumonia. Steatohepatitis with hemophagocytes. Disseminated intravascular coagulation. Cause of Death Organic Dysfunction Multiple-Shock Septic- abdominal-pelvic infection Endometritis by Actinomyces israelii. Results: Pelvic actinomycosis is an uncommon, opportunistic infection with a non-specific clinical course. It must be considered as a differential diagnosis in infiltrative processes suggestive of pelvic neoplasms. It presents a good evolution in the early diagnosis, with a response to beta-lactams. Schizophrenic patients show higher rates of serious infections than in the general population, since they are not aware of pain, which has an impact on morbidity and mortality, so it is suggested to perform interdisciplinary work and include in the medical controls the areas of hygiene, diet, activities, treatment of comorbid diseases and vaccines. Conclusion: The psychiatric pathology of the patient, caused that the evolution of the pathology is torpid in the absence of a clinical setting that guides tutors and doctors to the diagnosis.

THU0176 Golimumab 5-Year Safety: an Analysis of Pooled Data from the Long Term Extensions of Randomized, Double-Blind, Placebo-Controlled Studies in Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis

ObjectivesTo present analysis of pooled data through approx 5yrs of follow-up from 5 completed golimumab (GLM) Ph3 SC trials across rheumatological indications.MethodsSC placebo (PBO) or GLM (50mg or100mg) was administered...

Análise sistemática da influência do antifator de necrose tumoral [anti-TNF] sobre as taxas de infecção em pacientes com artrite reumatoide

ObjectiveThe present article aims to provide a systematic review of the influence of anti- tumor necrosis factor (TNF) on infection rates in patients with rheumatoid arthritis (RA). MethodMedline was searched to obtain quality control information on infection rates in RA patients treated with anti-TNF. ResultsA high proportion of RA patients are now established users of anti-TNF agents. Data from national registries in European countries of patients with RA treated with anti-TNF suggest that biological therapies are closely linked to sepsis. Although previous studies reported a higher risk of infections, there are now emerging data with longer duration of follow-up that suggested an adjusted hazard risk of 1.2. Elderly patients and those with longstanding disease may have a higher rate of serious infections compared to their coun- terparts who were younger with early disease. There are now emerging data to suggest that anti-TNF therapy is associated with the development of neutropenia shortly after the commencement of treatment. The biologic registries found that RA patients treated with monoclonal antibodies are at increased risk of tuberculosis (TB) compared to those on TNF receptor blockers. This risk of infection needs to be weighed against the established ben- efits of TNF blockers. ConclusionCurrent evidence suggests that anti-TNF treatment in RA is closely linked to infection. Patients need to be aware of the risk of infection together with the established benefits of TNF blockers in order to give informed consent for treatment.

A systematic review of the influence of anti-TNF on infection rates in patients with rheumatoid arthritis

ObjectiveThe present article aims to provide a systematic review of the influence of anti-tumor necrosis factor (TNF) on infection rates in patients with rheumatoid arthri- tis (RA). MethodMedline was searched to obtain quality control information on infection rates in RA patients treated with anti-TNF. ResultsA high proportion of RA patients are now established users of anti-TNF agents. Data from national registries in European countries of patients with RA treated with an- ti-TNF suggest that biological therapies are closely linked to sepsis. Although previous studies reported a higher risk of infections, there are now emerging data with longer duration of follow-up that suggested an adjusted hazard risk of 1.2. Elderly patients and those with longstanding disease may have a higher rate of serious infections compared to their counterparts who were younger with early disease. There are now emerging data to suggest that anti-TNF therapy is associated with the development of neutrope- nia shortly after the commencement of treatment. The biologic registries found that RA patients treated with monoclonal antibodies are at increased risk of tuberculosis (TB) compared to those on TNF receptor blockers. This risk of infection needs to be weighed against the established benefits of TNF blockers. ConclusionCurrent evidence suggests that anti-TNF treatment in RA is closely linked to infection. Patients need to be aware of the risk of infection together with the estab- lished benefits of TNF blockers in order to give informed consent for treatment.

Efficacy and Safety of Ocrelizumab in Active Proliferative Lupus Nephritis: Results From a Randomized, Double‐Blind, Phase III Study

To investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis (LN). Patients were randomized 1:1:1 to receive placebo, 400 mg ocrelizumab, or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15, followed by a single infusion at week 16 and every 16 weeks thereafter, accompanied by background glucocorticoids plus either mycophenolate mofetil (MMF) or the Euro-Lupus Nephritis Trial (ELNT) regimen (cyclophosphamide followed by azathioprine). The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebo-treated patients. We report week 48 efficacy data for patients receiving ≥32 weeks of treatment (n = 223) and safety results for all treated patients (n = 378). The overall renal response rate was 54.7%, 66.7%, 67.1%, and 66.9% in the placebo-treated, 400 mg ocrelizumab-treated, 1,000 mg ocrelizumab-treated, and combined ocrelizumab-treated groups, respectively. The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7% (95% confidence interval [95% CI] -0.8, 26.1) (P = 0.065), with similar differences observed for both ocrelizumab-treated groups. Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen, but not in those receiving background MMF. A numerically greater proportion of ocrelizumab-treated patients had a ≥50% reduction in the urinary protein:urinary creatinine ratio at 48 weeks compared with placebo-treated patients (placebo-treated patients, 58.7%; 400 mg ocrelizumab-treated patients, 70.7%; 1,000 mg ocrelizumab-treated patients, 68.5%). Serious adverse events occurred in 27.2% of placebo-treated patients, 35.7% of 400 mg ocrelizumab-treated patients, and 22.0% of 1,000 mg ocrelizumab-treated patients. Corresponding serious infection rates (events/100 patient-years) were 18.7 (95% CI 12.2, 28.7), 28.8 (95% CI 20.6, 40.3), and 25.1 (95% CI 17.4, 36.1), respectively. The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen. In patients with active LN, overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo. Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF.

SAT0133 Golimumab 3-year safety update: An analysis of pooled data from the long term extensions of randomized, double-blind, placebo-controlled studies in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis

ObjectivesTo present analysis of pooled data through approx 3yrs of follow-up from 5 ongoing golimumab (GLM) Ph3 SC trials across rheumatological indications and through 1yr in a completed Ph2 RA...

FRI0131 Mannose binding lectin (MBL) deficiency is a major risk factor for multiple serious infections (SI) in rheumatoid arthritis

BackgroundInfection is the leading cause of death in RA. Increasing age and use of corticosteroids (CS) are known risk factors (RF) for serious infection (SI). To what extent defects in...

Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a forty‐eight–week randomized, double‐blind, placebo‐controlled, parallel‐group phase III trial

To evaluate the efficacy and safety of treatment with ocrelizumab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and an inadequate response to MTX. STAGE was a phase III randomized, double-blind, parallel-group international study to evaluate the safety and efficacy of ocrelizumab compared with placebo in patients with active RA continuing MTX treatment. Patients receiving stable doses of MTX were randomized to receive 2 infusions of placebo (n = 320), ocrelizumab 200 mg (n = 343), or ocrelizumab 500 mg (n = 343) on days 1 and 15 as well as weeks 24 and 26. Coprimary end points were the proportion of patients with an American College of Rheumatology 20% improvement criteria (ACR20) response at weeks 24 and 48. Secondary end points included the change from baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70 responses. The ACR20 response rates were 35.7% in the placebo group, 56.9% in the ocrelizumab 200 mg group, and 54.5% in the ocrelizumab 500 mg group at 24 weeks, and 27.6%, 58.3%, and 62.1%, respectively, at 48 weeks (P < 0.0001 versus placebo for each dose at both time points). At week 48, both of the ocrelizumab doses improved the ACR50 and ACR70 response rates 3-fold as compared with placebo and showed a statistically significant (P < 0.0001) reduction in joint damage progression relative to placebo (mean change in SHS reduced by 85% and 100% for the 200-mg and 500-mg doses, respectively). Rates of serious infection were comparable in the placebo (3.48 per 100 patient-years) and ocrelizumab 200 mg (3.54 per 100 patient-years) groups but were elevated in the ocrelizumab 500 mg group (8.66 per 100 patient-years). With both ocrelizumab doses, the primary end point was met, and the signs and symptoms of RA were significantly improved at weeks 24 and 48. Ocrelizumab also significantly inhibited the progression of joint damage. A higher rate of serious infections was observed with 500 mg of ocrelizumab as compared with ocrelizumab 200 mg or placebo.

Monoclonal gammopathy after liver transplantation: a risk factor for long-term medical complications other than malignancies

The aims of the study were to evaluate (i) the prevalence of MGUS in patients after liver transplantation (LT), (ii) the role of MGUS as a risk factor for malignancy and other medical complications after LT. One hundred and fifty consecutive patients were included in the study and followed prospectively after LT for more than 18 months. Eighteen patients had MGUS before LT, whereas 49 patients developed MGUS after LT ('de novo' MGUS). Thirty-six of these patients showed a MGUS along all the follow up after LT ('permanent' MGUS). In 31 patients, MGUS disappeared after LT ('transient' MGUS). No patient with MGUS developed B-malignant lymphoproliferative disorder and only one patient developed a myeloma after LT. Comparing patients with 'permanent' MGUS to patients with 'transient' MGUS or without MGUS after LT, the former group showed a higher rate of serious infections (30% versus 13%, P = 0.01), chronic kidney disease (CKD) (75% versus 44%, P = 0.001) and mortality (33% versus 17%, P = 0.04). Permanent MGUS was confirmed as an independent risk factor for serious infections and CKD by multivariate analysis. Permanent MGUS after LT does not entail a significant risk of malignancy, but it is associated with a higher risk of serious infections and CKD.