Risk Of Opportunistic Infections Research Articles

The role of trimethoprim/sulfamethoxazole in preventing opportunistic infections in systemic lupus erythematosus patients receiving low-level immunosuppressive treatment: an open-label, randomized, controlled trial

Objective: Systemic lupus erythematosus (SLE) patients receiving immunosuppressive therapy are at risk for opportunistic infections (OIs), particularly Pneumocystis pneumonia (PCP). This study aimed to evaluate the effectiveness of trimethoprim/sulfamethoxazole (TMP/SMX) as primary prophylaxis against OIs and its adverse effects in SLE patients receiving low-level immunosuppressive treatment in a real-world setting. Methods: This open-label randomized controlled trial enrolled SLE patients receiving low-level immunosuppressive treatment at Ramathibodi Hospital between May 2021 and December 2022. Patient demographics and relevant clinical data were collected. Participants were randomized 1:1 to receive TMP/SMX or no prophylaxis, with dose adjustments according to renal function. The incidences of TMP/SMX-sensitive OIs and adverse events were monitored for 12 months post-enrollment. Results: The trial was terminated early due to a high rate of adverse drug reactions (ADRs) associated with TMP/SMX. In total, 138 SLE patients receiving low-level immunosuppressive treatment were enrolled. Most patients (98.4%) were in disease remission. No TMP/SMX-sensitive OIs were observed in either group during the 12-month follow-up period. Among individuals receiving TMP/SMX, 10/70 (14.3%) developed ADRs. Of these 10 patients, eight experienced grade 1 ADRs, and two had grade 3 ADRs; all declined to resume prophylaxis. There were no deaths in the study. Conclusions: During the 12-month follow-up period, no TMP/SMX-sensitive OIs occurred in SLE patients receiving low-level immunosuppressive therapy, suggesting that primary prophylaxis with TMP/SMX may not significantly benefit this population. The high rate of ADRs observed underscores the need for clinicians to carefully consider the risks and benefits of TMP/SMX prophylaxis in these patients.

Executive Summary: State-of-the-Art Review: Unintended Consequences: Risk of Opportunistic Infections Associated with Long-term Glucocorticoid Therapies in Adults.

Glucocorticoid-induced immunosuppression is linked to the dose, duration, and intensity, but the dose-dependent model may inaccurately predict the risk of opportunistic infections. We discuss details of glucocorticoid treatments to determine their effect on immune function and risk of opportunistic infections.

Antimicrobial Prophylaxis in Lymphoma by Chemotherapy Regimen

Treatment of lymphomas involves a wide variety of chemotherapy, immunotherapy, and targeted-agents tailored to disease biology and patient characteristics. Each of these regimens carry their own risk of opportunistic infections in an immunocompromised population. In addition to the treatment associated immunosuppression, lymphoma itself is immunosuppressive. Lymphoma associated immunosuppression is secondary to increased production of abnormal lymphocytes resulting in decreased production of normally functioning lymphocytes. Additionally, lymphoma cells induce both humoral and cellular immunosuppression through effects on numerous cytokines, T-cells, myeloid-derived suppressor cells, and macrophages. Clinical trials, patient co-morbidities, and institutional preferences all play a role in determining the preferred antimicrobial prophylaxis. While there is a paucity of data on systematic reviews and guidelines for standardized chemotherapy regimens in lymphoma patients, the efficacy and recommendations for antimicrobial prophylaxis in specific chemotherapy regimens for lymphoma has not been fully reviewed. According to the National Comprehensive Cancer Network, lymphoma is generally regarded as an ‘intermediate risk’ cancer with regards to overall infection risk. This results in discordance between research data and clinical practice. This is reiterated in the SIGNIFICANT trial which reported that while guidelines previously advised against fluoroquinolone prophylaxis in lymphoma and solid cancers, a survey of 3,600 physicians revealed that 45% routinely used fluoroquinolone prophylaxis despite these recommendations. This review article analyzes numerous research studies with summarization of findings and antimicrobial prophylaxis recommendations based on specific lymphoma chemotherapy regimens. With regards to each specific chemotherapy regimen assessed, indications for antibacterial, anti-viral, anti-fungal, and Pneumocystis jiroveci pneumonia (PJP) prophylaxis were determined for each regimen. The degree of immunosuppression and the necessary prophylaxis varies across different regimens and lymphoma subgroups; and thus, an individualized approach is necessary to optimize the supportive care during lymphoma treatment.

Advancements in the Management of Moderate-to-Severe Ulcerative Colitis: A Revised 2023 Korean Treatment Guidelines

Biologics such as anti-tumor necrosis factor agents have been the cornerstone for the treatment of inflammatory bowel disease but face limitations, including loss of response and risk of opportunistic infections and malignancies. Newer biologics and small molecules like vedolizumab, ustekinumab, and tofacitinib offer favorable safety profiles and demonstrate efficacy in moderate-to-severe ulcerative colitis. The landscape of the pipeline of biologics and small molecules is rapidly evolving. Upcoming drugs such as upadacitinib, filgotinib, and ozanimod show promise in recently concluded clinical trials, expanding the therapeutic options for ulcerative colitis. This review aims to discuss the medical treatment options available for the management of moderate-to-severe ulcerative colitis, with a focus on biologics and small molecules recommended in revised 2023 Korean guidelines.

Comparative risk of infections between JAK inhibitors versus TNF inhibitors among patients with rheumatoid arthritis: a cohort study

BackgroundTo compare infectious risk between JAK inhibitors (JAKis) versus TNF inhibitors (TNFis) among rheumatoid arthritis (RA) patients in Korea.MethodsUsing 2009–2019 Korea National Health Insurance Service database, we conducted a cohort study on RA patients initiating a JAKi or TNFi. The primary outcomes were herpes zoster (HZ), serious bacterial (SBI), and opportunistic infections (OI). Propensity-score fine-stratification (PSS) and weighting were applied to adjust for > 70 baseline covariates. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models comparing JAKi versus TNFi users.ResultsWe included 2963 JAKi initiators PSS-weighted on 5169 TNFi initiators. During a follow-up of 1.16 years, the most frequent type of infections was HZ with incidence rate (IR) per 100 person-years of 11.54 and 4.88 in JAKi and TNFi users, respectively. The IR of SBI was 1.39 and 1.32, respectively. The OI was rare with a majority being tuberculosis and showed an IR of 0.11 and 0.49 in JAKi and TNFi users, respectively. The PSS-weighted HR (95% CI) for individual types of infections was 2.37 (2.00–2.80) for HZ, 1.04 (0.71–1.52) for SBI, and 0.25 (0.09–0.73) for OI.ConclusionsThis population-based cohort study on RA patients treated with JAKi or TNFi in Korea showed an exceptionally high IR of HZ in both treatment groups compared to that from Western countries, with an approximately doubled risk associated with JAKi versus TNFi use. The risk of SBI was comparable, but the risk of OI, particularly tuberculosis, was less among JAKi than TNFi initiators.

Ikaros expression is associated with an increased risk of chronic graft-versus-host disease

Immune reconstitution after hematopoietic stem cell transplantation (HSCT) is a complex and extremely variable process. The Ikaros transcription factor plays an important role in hematopoiesis in several cell lines, especially in the lymphoid lineage. We hypothesized that Ikaros might influence immune reconstitution, and consequently, the risk of opportunistic infections, relapse, and graft versus host disease (GVHD). Samples were collected from the graft and from the peripheral blood (PB) of the recipients 3 weeks after neutrophil recovery. Real-time polymerase chain reaction (RT-PCR) was performed to analyze the absolute and relative Ikaros expression. Patients were divided into two groups, according to Ikaros expression in the graft and in the recipients’ PB based on the ROC curves for moderate/severe cGVHD. A cutoff of 1.48 was used for Ikaros expression in the graft, and a cutoff of 0.79 was used for Ikaros expression in the recipients’ PB. Sixty-six patients were included in this study. Median age of patients was 52 years (range 16–80 years), 55% of them were male, and 58% of them had acute leukemia. Median follow-up period was 18 months (range 10–43 months). There was no association between Ikaros expression and the risk of acute GVHD, relapse, or mortality. However, a significant association was observed with the risk of chronic GVHD. Higher Ikaros expression in the graft was associated with a significantly higher cumulative incidence (CI) of moderate/severe chronic GVHD according to the National Institute of Health (NIH) classification at two years (54% vs. 15% for patients with lower expression, P = 0.03). A higher Ikaros expression in the recipients’ PB 3 weeks after engraftment was also associated with a significantly higher risk of moderate/severe chronic GVHD (65% vs. 11%, respectively, P = 0.005). In conclusion, Ikaros expression in the graft and in the recipients’ PB after transplantation was associated with a higher risk of moderate/severe chronic GVHD. Ikaros expression should be evaluated in larger prospective trials as a potential biomarker for chronic GVHD.

Evaluation of possibility of cultivation of acid resistant bacteria on solid egg-based and agar cultural media.

The increase in the number of patients at risk for opportunistic infections caused by rare bacteria, which include individual representatives of acid-resistant bacteria (ARB), is a serious problem in modern health care. Significant difficulties in the etiological diagnosis of mycobacteriosis, nocardiosis, and actinomycosis are associated not only with the problem of identifying the main pathogens but also with certain difficulties in isolating pathogens from biological material. The research provides data on 402 strains of ARB, which were isolated from various biological materials obtained from patients during examination for tuberculosis. All samples of biological material were negative on the Mycobacterium tuberculosis complex. The isolates were identified on the MALDI-ToF mass spectrometer. The cultural characteristics of ARB were evaluated on the solid Löwenstein-Jensen egg-based culture media, universal chromogenic media, and 5% blood agar with lamb blood. The studies carried out indicate the possibility of culturing ARB representatives on agar media. At the same time, based on the comparison of the growth properties of ARB, it was found that the universal chromogenic media provides more acceptable conditions for the isolation of nontuberculous mycobacteria (NTM) compared to blood agar. The comparison of the growth rate of bacteria did not reveal significant differences for fastly growing NTM. For slowly growing species, the growth rate on blood agar was lower than on chromogenic media and on the Löwenstein-Jensen media. Thus, the use of a universal chromogenic media during incubation makes it possible to isolate and preidentify representatives of the ARB under the conditions of standard operating procedures of the microbiological laboratory.

Characteristics of Staphylococcus aureus Isolated from Patients in Busia County Referral Hospital, Kenya.

Staphylococcus aureus is an important pathogen associated with hospital, community, and livestock-acquired infections, with the ability to develop resistance to antibiotics. Nasal carriage by hospital inpatients is a risk for opportunistic infections. Antibiotic susceptibility patterns, virulence genes and genetic population structure of S. aureus nasal isolates, from inpatients at Busia County Referral Hospital (BCRH) were analyzed. A total of 263 inpatients were randomly sampled, from May to July 2015. The majority of inpatients (85.9%) were treated empirically with antimicrobials, including ceftriaxone (65.8%) and metronidazole (49.8%). Thirty S. aureus isolates were cultured from 29 inpatients with a prevalence of 11% (10.3% methicillin-susceptible S. aureus (MSSA), 0.8% methicillin resistant S. aureus (MRSA)). Phenotypic and genotypic resistance was highest to penicillin-G (96.8%), trimethoprim (73.3%), and tetracycline (13.3%) with 20% of isolates classified as multidrug resistant. Virulence genes, Panton-Valentine leukocidin (pvl), toxic shock syndrome toxin-1 (tsst-1), and sasX gene were detected in 16.7%, 23.3% and 3.3% of isolates. Phylogenetic analysis showed 4 predominant clonal complexes CC152, CC8, CC80, and CC508. This study has identified that inpatients of BCRH were carriers of S. aureus harbouring virulence genes and resistance to a range of antibiotics. This may indicate a public health risk to other patients and the community.

Coexistence of Competing Opportunistic Pathogens in Critically ill Patients with Advanced AIDS: A Case Report and Literature Review

Introduction: Opportunistic infections (OIs) are the leading causes of morbidity and mortality among HIV-infected individuals. The incidence of OIs is greater in antiretroviral treatment (ART) naive patients. As of 30 June 2021, 28.2 (73%) people with HIV/AIDS (PLWHA) were accessing antiretroviral therapy (ART) globally, leaving the remaining 27% PLWHA without ART at risk for OIs. Multiple opportunistic infections are caused due to the coexistence of competing opportunistic pathogens that confound clinical manifestations, investigative procedures, and management protocols. Case Presentation: In this report, we describe the case of a critically ill HIV female patient admitted to the ICU. The patient was diagnosed with multiple opportunistic infections and subsequently died after her illness progressed. Due to the paucity of information on the subject, we conducted a retrospective study of 1440 case records of HIV/AIDS critically ill patients to determine the incidence and spectrum of multiple opportunistic infections. We performed a review of the available medical literature relevant to the subject. Conclusion: Knowledge of such events would guide and enhance the physician's diagnostic and management strategies, especially in resource limited regions.

Takayasu's disease: an underdiagnosed entity in Sub-Saharan Africa. Report of five Gabonese cases

RésuméLa maladie de Takayasu est une vascularite affectant de façon préférentielle l'aorte et ses principales branches. Mycobacterium tuberculosis peut notamment être un facteur déclenchant du développement de la maladie de Takayasu par une réaction d'hypersensibilité. Le Maghreb et l'Afrique du Sud cumulent le plus grand nombre d'observations africaines, alors qu'entre les deux, en Afrique subsaharienne, les données parcellaires de la maladie font penser que la prévalence de la maladie est probablement sous-estimée/sous-diagnostiquée. Nous en rapportons 5 observations gabonaises.

POS-087 SEVERE SEPSIS AND DEATH DUE TO MYCOBACTERIUM FORTUITUM IN A PATIENT WITH CHRONIC KIDNEY DISEASE ON MAINTENANCE HEMODIALYSIS

Patients with chronic kidney disease (CKD) or end-stage renal disorder (ESRD) have impaired cell mediated immunity. Despite adequate care and caution, the risk of opportunistic infections is higher in this patient population. Apart from the Mycobacterium tuberculosis certain nontuberous mycobacterium are reported causing mild to severe disseminated infection.

Long-Term Effects of Radiation on Lymphocytes and Risk of Opportunistic Infections.

ObjectivesLymphocytes are very sensitive to ionizing radiation. The long-term effects and the risk of permanent immune compromise are not well defined in spite of more than a century of therapeutic radiation. The contemporary analysis is made more difficult in that most patients also receive immunosuppressive chemotherapy.MethodsCohort-all patients that underwent a prostate biopsy from 2002 to 2007. Those (n=1118) with at least two blood counts, with one at a minimum of 10 years after biopsy, were included. We identified three groups: those that received no treatment (due to benign biopsy findings or active surveillance), those undergoing prostate cancer surgery, and those undergoing radiation therapy. Blood counts were collected and analyzed for differences with a median follow-up of 178 months. Also evaluated was the risk of opportunistic infections.ResultsThe median granulocyte count gradually increased with time, with no difference between the groups. Overall, the median lymphocyte count decreased from baseline over time (with a slight rise at 20 years). For the no treatment and surgery groups, the lymphocyte counts declined, but due to the initial decline after radiation therapy, that group saw a slow improvement. By 20 years, there was no difference between the groups. Most patients’ counts remained in the normal range throughout. The risk of defined opportunistic infections was low (12%) with no difference between the groups.ConclusionPelvic radiation has minimal lasting effects on lymphocyte and granulocyte counts. In addition, patients receiving radiation do not appear to be significantly immunocompromised.

Laryngeal Histoplasmosis in an Immunocompromised Host

Laryngeal histoplasmosis is a rare manifestation of histoplasmosis infection and presents as a diagnostic challenge. It has been documented to occur in immunocompromised and immunocompetent hosts. This is a case of laryngeal histoplasmosis in a patient with idiopathic CD4 lymphocytopenia, an immunocompromising condition that presents similarly to HIV. There is no known cause or standardized treatment of idiopathic CD4 lymphocytopenia, which leaves patients at risk for opportunistic infections and malignancy.

The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids.

Immune-related adverse events (irAEs) often require treatment with high-dose systemic steroids (SS) and other immunosuppressive agents (ISAs). NCCN Guidelines recommend prophylactic antibiotics for Pneumocystis jirovecii pneumonia (PJP) for patients receiving prolonged SS/ISAs. However, there is a paucity of evidence regarding the incidence of opportunistic infections (OIs) and non-OIs and the role of prophylactic antibiotics in patients on SS/ISAs for irAEs. A retrospective analysis was conducted of patients treated using immune checkpoint inhibitor (ICI) therapy at 5 MedStar Health hospitals from January 2011 to April 2018. OIs were defined per the Infectious Diseases Society of America guidelines for the prevention and treatment of OIs in patients with HIV. The study cohort included patients who received ≥20 mg daily of a prednisone equivalent for ≥4 weeks to manage irAEs. The study cohort identified 112 (15%) of 758 total patients treated using ICIs. Baseline characteristics included the following: median age was 64 years, 74% (n=82) of patients were White, 89% (n=100) had an ECOG performance status ≤1, 61% (n=68) had melanoma, 19% (n=21) had non-small cell lung cancer, 45% (n=50) were treated using an anti-PD-(L)1 ICI, and 33% (n=37) were treated using an anti-PD-1/anti-CTLA-4 combination. The median starting SS dose was 100 mg of a prednisone equivalent, and 25% of patients required additional ISAs, with infliximab (n=15) and mycophenolate mofetil (n=9) being the most common. We found that 20% (n=22) of patients developed any infection, including 7% (n=8) with OIs (oral candidiasis [n=4], nondisseminated varicella zoster infection [n=2], PJP [n=1], and Listeria monocytogenes endophthalmitis [n=1]) and 13% (n=14) with non-OIs (most common: Clostridium difficile and pneumonia [n=5 each]). PJP prophylaxis with sulfamethoxazole/trimethoprim was given to 13% (n=14) patients, of whom 43% (n=6) developed OIs/non-OIs. Our study highlights the fundamental issues for patients on ICI therapy who require SS/ISAs for irAEs: the degree of immunosuppression and the relative risk of OI. We noted a low incidence of OIs overall and breakthrough infections despite PJP prophylaxis. We question whether PJP prophylaxis is efficacious or necessary. Prospective trials are required to answer these questions.

The Risk of Opportunistic Infections in Patients with Inflammatory Bowel Disease

Objective: Immunity-related issues are the main concerns of patients undergoing in-flammatory bowel disease (IBD) treatment. The treatment of IBD during the last decade has evolved due to the ever-increasing utilization of immunomodulators, which has caused the poten-tial of contracting opportunistic infections to become the main immunity concern for patients affected by IBD. Methods: Studies on opportunistic infections in patients with IBD identified in databases such as Google Scholar, PubMed, and Scopus were reviewed and included. Results: IBD patients are a high-risk population for opportunistic infections, with age being a significant factor. The primary therapy for IBD patients includes the suppression of the immunity system, together with immunodeficiency and biological treatments, which, first of all, must be standardized. Since treatment with suppressive medicine, which is the original method for curing IBD, causes viral infections and the growth of various bacteria, factors suppressing the body's immunity system must be temporarily suspended, or the consumption dosage of sensitive antibi-otics should be reduced. Biological treatment and anti-integrin antibodies will lead to the danger of being affected by opportunistic infections in patients with IBD. Conclusion: Worldwide research society must conduct further research into a therapeutic strategy for IBD patients to reduce susceptibility and the risk of opportunistic infection. Information about how these individuals and the medicines they were given reacted to different infections and more detailed clinical observations are required.

Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms.

The capecitabine/temozolomide (CAPTEM) regimen has significant activity in advanced neuroendocrine tumors (NETs). Questions exist regarding activity in pancreatic versus nonpancreatic NETs, risk of opportunistic infections, long-term myelotoxicity, and safety of prolonged treatment duration. Analysis of large patient cohorts is needed for the evaluation of rare toxicities and assessment of risk factors. We conducted a retrospective study of all patients with advanced NETs seen at Moffitt Cancer Center between January 2008 and June 2019 who received treatment with CAPTEM. A total of 462 patients were eligible. The objective radiographic response rate was 46%, and the disease control rate was 81%. Median progression-free survival (PFS) was 18 months (95% CI, 14.0-21.9 months) and median overall survival was 51 months (95% CI, 42.8-59.2 months): 62 months in well-differentiated NETs versus 14 months in poorly differentiated neuroendocrine carcinomas (P<.0001). Patients with primary pancreatic tumors had the highest partial response rates and longest median PFS. Incidences of grade 4 thrombocytopenia and neutropenia were 7% and 3%, respectively, and substantially higher in women than men (P=.02 and P=.004, respectively). Only 1 case (0.2%) of suspected Pneumocystis pneumonia (PCP) was observed in a patient receiving corticosteroids. Three patients developed myelodysplastic disease, all of whom had received prior peptide receptor radiotherapy (PRRT). There were no acute treatment-related deaths; 1 patient died 2 months after a thrombocytopenic bleed. The CAPTEM regimen is exceptionally safe. Efficacy is particularly robust in well-differentiated pancreatic NETs. Severe myelotoxicity is rare; the risk of grade 4 cytopenias is significantly increased in women, and therefore sex-based dosing should be considered. There were no cases of myelodysplastic syndromes, except among patients who had received PRRT, a known risk factor. The risk of PCP is negligible.

Tuberculosis is a Common Cause of Post-Liver Transplant Ascites: An Observational Study

Background Ascites is expected to resolve within 2 to 4 weeks following orthotopic liver transplantation. New-onset ascites after transplant is associated increased morbidity and affects quality of life. The risk of opportunistic infections is high in transplant recipients due to immunosuppressive drugs. Objective The objective was to assess the incidence of new-onset ascites in the transplant recipients and describe the cause and course of the same. Methods We retrospectively collected data of all the patients who underwent liver transplantation at our center from April 1, 2020 to April 1, 2021. The details of patients developing ascites post-liver transplantation were retrieved. The patients were followed up for 1 year after transplant. Results A total of 95 patients underwent living donor liver transplantation at our center. The incidence of new-onset ascites was 8.42% (8/95). Six out eight patients were diagnosed with tubercular ascites of whom one had disseminated tuberculosis. None of the patients had concomitant pulmonary tuberculosis. Ascites secondary to hypoalbuminemia was reported in two patients. Immunoglobulin A nephropathy and tacrolimus therapy were the underlying causes of proteinuria. Conclusion Tuberculosis was the leading cause of ascites in post-transplant period in our study. Tuberculosis should be considered as a differential diagnosis while evaluating these patients especially in the Asia-Pacific region. Being a potentially curable cause, timely diagnosis and treatment significantly improves graft survival.

Human Immunodeficiency Virus (HIV) infection with Multiple Comorbidities in COVID-19 Pandemic Era: A Case Report

Coronavirus disease-19 (COVID-19) and Human Immunodeficiency Virus (HIV) were pandemic diseases that affected the healthcare system worldwide. Decline immune system in HIV and accompanying opportunistic infection may worsen the outcome and prognosis of COVID-19 infection. Comprehensive diagnosis and treatment were crucial with HIV patients with a very low immune response. This is our first case report of 50 years old man recently known with HIV and confirmed COVID-19 from PCR swab at once. We found several comorbidities through a comprehensive examination of clinical and laboratory, such as bicytopenia (anemia and thrombocytopenia), acute renal failure, increased liver transaminase, and coagulation disorder (increased PT/APTT) D-dimer), hypoalbuminemia and extremely low CD4. Oral candidiasis, chronic B hepatitis, and lung tuberculosis also present as opportunistic infections in this patient. One dose of antiviral oseltamivir was given each day interval (considering the patient's renal function) accompanied with immediate resuscitation, multivitamins, fluconazole, and cotrimoxazole given. After resolving an acute condition, oral tuberculosis treatment was given, continued with antiretroviral therapy, and advised the patient to routine control in the outpatient department. Future research should address the significance of CD4 lymphocyte count or viral load to measure patients with HIV's immune system and clinical status, risk of opportunistic infection, and prognostic in this pandemic COVID-19 era.

Abstract 11844: Viral Gene Signatures in Patients With Cardiomyopathy After Chemotherapy

Introduction: Chemotherapy for hematologic malignancies can cause severe cardiomyopathy. Chemotherapeutic agents also induce immune suppression increasing the risk of opportunistic infections. Hypothesis: We have hypothesized that immunosuppression after chemotherapy increases opportunistic viral infections, myocarditis and cardiomyopathy. Methods: Viral gene sequences were identified using an unbiased high-throughput sequencing approach of patient blood samples following chemotherapy treatment for hematological malignancies (N = 28). Detected viral sequences were correlated with cardiac ejection fraction (LVEF) measured before and after treatment. Results: In a blinded analysis undertaken by two investigators viral sequences were identified in blood samples from patients after chemotherapy. Low levels of Influenza A, orthomyxovirus and Avian Paramyxovirus sequences were detected but identified individual virus sequences did not have a significant correlation to reduced LVEF post chemotherapy (r = 0.177-0.293). Detected sequences for all RNA viruses combined did indicate some correlation with LVEF, r = 0.621, suggesting potential for nonspecific RNA virus detection ( p &lt; 0.0078). In a secondary broad screen, data mining was performed including all detectable viral sequences without the filtering of human related sequences. In this broad analysis a significant correlation was detected for Paramyxovirus with reduced cardiac LVEF (r = 0.592 post, compared to r = 0.464 prior to chemotherapy; P &lt; .0096). For detected Orthomyxovirus sequences correlations were similar for LVEF pre- and post- chemotherapy (R = 0.483, P &lt; 0.0451). Retroviruses reads were increased but suspect due to human genome retrovirus sequences (R= 0.512; P &lt; 0.0351). No correlation was seen for Anellovirus, a DNA virus. Reduced LVEF did not correlate with chemotherapy (p = NS). Conclusions: This is the first report of screening for RNA viruses in the circulating blood of patients post chemotherapy using a high-throughput sequencing approach. Influenza Orthomyxovirus and Avian Paramyxovirus sequences were detectable in patients with reduced LVEF after chemotherapy. Further analysis for RNA virus infections in cardiomyopathy after chemotherapy is warranted.

Safety and efficacy of combining biologics or small molecules for inflammatory bowel disease or immune-mediated inflammatory diseases: A European retrospective observational study.

Background and aimsFew data are available regarding the combination of biologics or small molecules in inflammatory bowel disease (IBD) patients. We report safety and efficacy of such combinations through a retrospective multicentre series.MethodsCombination therapy was defined as the concomitant use of two biologics or one biologic with a small molecule. Patient demographics, disease characteristics and types of combinations were recorded. Safety was evaluated according to the occurrence of serious infection, opportunistic infection, hospitalisation, life‐threatening event, worsening of IBD or immune‐mediated inflammatory diseases (IMID), cancer and death. Efficacy was evaluated as the physician global assessment of the combination and comparison of clinical/endoscopic scores of IBD/IMID activity prior and during combination.ResultsA total of 104 combinations were collected in 98 patients. Concomitant IMID were present in 41 patients. Reasons for starting combination therapy were active IBD (67%), active IMID or extra‐intestinal manifestations (EIM) (22%), both (10%) and unclassified in 1. Median duration of combination was 8 months (interquartile range 5–16). During 122 patient‐years of follow‐up, 42 significant adverse events were observed, mostly related to uncontrolled IBD. There were 10 significant infections, 1 skin cancer and no death. IBD disease activity was clinically improved in 70% and IMID/EIM activity in 81% of the patients. Overall, combination was continued in 55% of the patients.ConclusionsCombination of biologics and small molecules in patients with IBD and IMID/EIM seems to be a promising therapeutic strategy but is also associated with a risk of opportunistic infections or infections leading to hospitalisation in 10%.