Immunocompromised State Research Articles

Evaluating in vivo effectiveness of sotrovimab for the treatment of Omicron subvariant BA.2 versus BA.1: a multicentre, retrospective cohort study

BackgroundIn vitro data suggested reduced neutralizing capacity of sotrovimab, a monoclonal antibody, against Omicron BA.2 subvariant. However, limited in vivo data exist regarding clinical effectiveness of sotrovimab for coronavirus disease 2019 (COVID-19) due to Omicron BA.2.MethodsA multicentre, retrospective cohort study was conducted at three Canadian academic tertiary centres. Electronic medical records were reviewed for patients ≥ 18 years with mild COVID-19 (sequencing-confirmed Omicron BA.1 or BA.2) treated with sotrovimab between February 1 to April 1, 2022. Thirty-day co-primary outcomes included hospitalization due to moderate or severe COVID-19; all-cause intensive care unit (ICU) admission, and all-cause mortality. Risk differences (BA.2 minus BA.1 group) for co-primary outcomes were adjusted with propensity score matching (e.g., age, sex, vaccination, immunocompromised status).ResultsEighty-five patients were included (15 BA.2, 70 BA.1) with similar baseline characteristics between groups. Adjusted risk differences were non-statistically significant between groups for 30-day hospitalization (− 14.3%; 95% confidence interval (CI): − 32.6 to 4.0%), ICU admission (− 7.1%; 95%CI: − 20.6 to 6.3%), and mortality (− 7.1%; 95%CI: − 20.6 to 6.3%).ConclusionsNo differences were demonstrated in hospitalization, ICU admission, or mortality rates within 30 days between sotrovimab-treated patients with BA.1 versus BA.2 infection. More real-world data may be helpful to properly assess sotrovimab’s effectiveness against infections due to specific emerging COVID-19 variants.

P1155 Impact of COVID19 pandemic and vaccination among IBD patients: a multinational cross sectional survey

Abstract Background The aim of current study is to evaluate impact of COVID19 pandemic and vaccination against it on the course and symptoms of IBD. Methods During a six months’ period, all of the IBD cases who attend in outpatient clinics of nine referral centers in 6 countries include and request to fill a questionnaire about their demographic characters and pattern of IBD, any history of involvement with COVID19 and their vaccination history. Results overall 812 cases from 16 countries included (52.4% male) with average age of 36.8 y (range 7 – 76). 68.5% of participants diagnosed as UC and 29.5% as CD. 80% of participants have vaccinated against COVID19 (average 2.3 times, range 1 – 5). Among those who vaccinated (group A) 31.6% experienced side effects and complication without any mortality. The most common complications of vaccination include fever (24%), fatigue (20.1%) and anorexia 8.6%. The most common reasons for vaccination refusal (group B) were fear of vaccine complication (55.5%), no believe in vaccine protection (29.6%) and fear of immunocompromised condition (17.9%). In group A overall 61% of participants involved with COVID 19 (36.2% after vaccination) in comparison with 48.1% in group B (P = 0.0052). Most of the involvements in both groups were not sever and just a minority of patients admitted to hospital (10% in group A and 6.4% in group B). Following COVID involvement, 45.1% of cases suffered with GI symptoms (mostly diarrhea (72.5%) and abdominal pain (64.5%)). In group A, 37.3% of involvements have happened before vaccination. Conclusion Vaccination against COVID19 is safe and effective among IBD patients and following vaccination, most of complications are minor and negligible. In case of COVID involvement, it would not be serious and there is no need to hold the medications. Among IBD patients, the most common reason for vaccination refusal is fear of vaccine side effect.

Clinical courses and outcomes of COVID-19 associated pulmonary aspergillosis in 168 patients with the SARS-CoV-2 omicron variant

PurposeWe aimed to analyze the clinical features of COVID-19-associated pulmonary aspergillosis (CAPA) during the SARS-CoV-2 Omicron variant pandemic and to reveal the risk factors for CAPA and death.MethodsA retrospective cohort study was conducted on 168 CAPA patients from December 8, 2022 to January 31, 2023. 168 COVID-19 patients without secondary fungal infection during this period were matched 1:1 using propensity score matching as controls.ResultsThe incidence of CAPA was 3.8% (168/4421). Compared with patients without fungal infection, CAPA patients had a higher mortality (43.5% vs. 10.1%, P < 0.001). Patients in the death group (n = 73) were more likely to be admitted to ICU (91.8% vs. 26.3%, p < 0.001), had a shorter ICU length of hospitalization (10 (IQR, 6 ~ 16.5) days vs. 14 (IQR, 8 ~ 37) days, p = 0.012). Immunocompromised status (p = 0.023), NLR ≥ 5.7 (p = 0.004), CRP ≥ 50 mg/L (p = 0.043), and the number of antibiotics ≥ 3 (p < 0.001) were all risk factors for CAPA; NLR ≥ 5.7 (p = 0.009) and the number of antibiotics ≥ 3 (p = 0.018) were all independent risk factors for death.ConclusionsDuring the Omicron variant pandemic, CAPA increased death and ICU length of hospitalization. The risk factors of CAPA and death obtained from the study can help us further understand the disease characteristics of CAPA and better guide our clinical decision-making.

A maintenance hemodialysis patient complicated with hypogammaglobulinemia presenting typical COVID-19 pneumonia CT findings: a case report

BackgroundWith the widespread use of the vaccine and the predominance of the Omicron strain, the number of patients presenting with typical coronavirus-infection disease 2019 (COVID-19) pneumonia on computed tomography (CT) has decreased dramatically. This has also been true for hemodialysis patients.Case reportA 72-year-old female maintenance hemodialysis patient with hypogammaglobulinemia was diagnosed with COVID-19 based on a nasopharyngeal swab severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) polymerase chain reaction (PCR) test. She had previously received five doses of COVID-19 BNT162b2 vaccine. Initially, the patient had only a slight fever, mild sore throat and sputum, and molnupiravir 1600 mg/day was administered for 5 days. No high fever was observed during that period. On day 11 after diagnosis, bloody sputum was observed, and by day 13 the cough had worsened and her CRP level had increased to 13.10 mg/dL. Chest CT performed on the same day showed multiple subpleural ground-glass-like shadows typical of COVID-19 pneumonia predominantly in the right lung. She was immediately admitted to the hospital, where her temperature rose to 38.4 °C. Intravenous remdesivir 100 mg/day was administered for 5 days. This resolved her fever and the bloody sputum disappeared. She was discharged from the hospital without sequelae on the 21st day after diagnosis.ConclusionWe experienced a case of typical COVID-19 pneumonia in a patient on maintenance hemodialysis who had received five doses of COVID-19 BNT162b2 vaccine. There was a flare-up of symptoms after administration of molnupiravir, suggesting that a hypogammaglobulinemia complication was involved. This highlights the need for attention to its potential transition to severe disease when patients with hypogammaglobulinemia or other highly immunocompromised conditions are affected by COVID-19.

Thamnostylum piriforme, a novel etiological agent of superficial mycosis

Fungi are opportunistic eukaryotic entities often taking advantage of susceptibilities offered by a host due to its immunocompromised status, changed microbiome, or ruptured physical barriers and eventually cause infections. They either invade the skin superficially or are deep-seated. Superficial mycosis affects the skin, hair, and nails inhabiting the outermost layer, stratum corneum. In the present study, we report a case of superficial mycosis (onychomycosis in particular) in a 45-year-old immunocompetent man who was an ex-defense personnel and presently serving as a security guard at the University of Jammu, District Jammu, Jammu and Kashmir, India. The infection evolved 17 years ago and negatively affected the quality of life of the patient. For the identification of the causal agent, direct microscopy, cultural, micro-morphological, molecular characterization (ITS sequencing), and phylogenetic analysis were taken into account. A mucoralean fungal species, Thamnostylum piriforme, was isolated from the fingernails (left hand) of the investigated patient, which represents a new global report as the causal agent of superficial mycosis. In vitro antifungal susceptibility testing showed T. piriforme sensitivity to itraconazole, amphotericin B and ketoconazole while resistance to fluconazole. Careful selection of optimal therapy for fungal infection based primarily on correct identification and antifungal susceptibility testing could provide effective results during treatment against these opportunistic human fungal pathogens.

Cycle threshold dynamics of non-severe acute respiratory coronavirus virus 2 (SARS-CoV-2) respiratory viruses.

Many providers use severe acute respiratory coronavirus virus 2 (SARS-CoV-2) cycle thresholds (Ct values) as approximate measures of viral burden in association with other clinical data to inform decisions about treatment and isolation. We characterized temporal changes in Ct values for non-SARS-CoV-2 respiratory viruses as a first step to determine whether cycle thresholds could play a similar role in the management of non-SARS-CoV-2 respiratory viruses. Retrospective cohort study. Brigham and Women's Hospital, Boston. We retrospectively identified all adult patients with positive nasopharyngeal PCRs for influenza, respiratory syncytial virus (RSV), parainfluenza, human metapneumovirus (HMPV), rhinovirus, or adenovirus between January 2022 and March 2023. We plotted Ct distributions relative to days since symptom onset, and we assessed whether distributions varied by immunosuppression and other comorbidities. We analyzed 1,863 positive samples: 506 influenza, 502 rhinovirus, 430 RSV, 219 HMPV, 180 parainfluenza, 26 adenovirus. Ct values were generally 25-30 on the day of symptom onset, lower over the ensuing 1-3 days, and progressively higher thereafter with Ct values ≥30 after 1 week for most viruses. Ct values were generally higher and more stable over time for rhinovirus. There was no association between immunocompromised status and median intervals from symptom onset until Ct values were ≥30. Ct values relative to symptom onset for influenza, RSV, and other non-SARS-CoV-2 respiratory viruses generally mirror patterns seen with SARS-CoV-2. Further data on associations between Ct values and viral viability, transmissibility, host characteristics, and response to treatment for non-SARS-CoV-2 respiratory viruses are needed to determine how clinicians and infection preventionists might integrate Ct values into treatment and isolation decisions.

Glycylglycine promotes the solubility and antigenic utility of recombinant HCV structural proteins in a point-of-care immunoassay for detection of active viremia

BackgroundAlthough E. coli is generally a well-opted platform for the overproduction of recombinant antigens as heterologous proteins, the optimization of expression conditions to maximize the yield of functional proteins remains empirical. Herein, we developed an optimized E. coli (BL21)-based system for the overproduction of soluble immunoreactive HCV core/envelope proteins that were utilized to establish a novel immunoassay for discrimination of active HCV infection.MethodsThe core/E1-E2 genes were amplified and expressed in E. coli BL21 (DE3) in the absence/presence of glycylglycine. The antigenic performance of soluble proteins was assessed against 63 HCV-seronegative (Ab−) sera that included normal and interferent sera (HBV and/or chronic renal failure), and 383 HCV-seropositive (Ab+) samples that included viremic (chronic/relapsers) and recovered patients’ sera. The color intensity (OD450) and S/Co values were estimated.ResultsThe integration of 0.1–0.4M glycylglycine in the growth media significantly enhanced the solubility/yield of recombinant core and envelope proteins by ~ 225 and 242 fold, respectively. This was reflected in their immunoreactivity and antigenic performance in the developed immunoassay, where the soluble core/E1/E2 antigen mixture showed 100% accuracy in identifying HCV viremic sera with a viral RNA load as low as 3800 IU/mL, without cross-reactivity against normal/interferent HCV-Ab−sera. The ideal S/Co threshold predicting active viremia (> 2.75) showed an AUC value of 0.9362 (95% CI: 0.9132 to 0.9593), with 87.64, 91.23% sensitivity and specificity, and 94.14, 82.11% positive and negative predictive values, respectively. The different panels of samples assayed with our EIA showed a good concordance with the viral loads and also significant correlations with the golden standards of HCV diagnosis in viremic patients. The performance of the EIA was not affected by the immunocompromised conditions or HBV co-infection.ConclusionThe applicability of the proposed platform would extend beyond the reported approach, where glycylglycine, low inducer concentration and post-induction temperature, combined with the moderately-strong constitutive promoter enables the stable production of soluble/active proteins, even those with reported toxicity. Also, the newly developed immunoassay provides a cost-effective point-of-care diagnostic tool for active HCV viremia that could be useful in resource-limited settings.

Evaluating Kaposi Sarcoma in Kidney Transplant Patients: A Systematic Review and Meta-Analysis.

Kaposi's sarcoma (KS) is a malignancy that commonly appears as lesions on the skin or mucosal surfaces but can also develop in other organs. This cancer is usually caused by the human herpesvirus 8 (HHV-8), recently known as Kaposi's sarcoma-associated herpesvirus (KSHV). KS is rare in the general population but can develop in kidney transplant recipients with varying incidence due to immunocompromised status from immunosuppression. The main aim of the present systematic review was to identify the prevalence and treatment of KS in kidney transplant patients. PubMed, Cochrane Library, and Google Scholar databases were searched for studies until October 2023. Full-text studies with similar research objectives were included, while non-English articles, reviews, case reports, ongoing clinical trials, and studies evaluating KS in HIV patients or after other solid organ transplants were excluded. All studies were observational; therefore, methodological quality was assessed using the Newcastle-Ottawa Scale. The statistical analyses were performed with the Comprehensive Meta-Analysis (CMA) software (Biostat, Inc.Englewood, NJ). The pooled analysis from the 15 studies includedshowed that KS develops in 1.5% of kidney transplant recipients and is more prevalent in African (1.7%) and Middle Eastern (1.7%) recipients than in Western recipients (0.07%). KS was also significantly more prevalent among male recipients than female recipients (OR: 2.36; p < 0.0001). Additionally, cyclosporine-based immunosuppression accounts for most KS incidences (79.6%) compared to azathioprine-based immunosuppression (28.2%). Furthermore, reduction or withdrawal of immunosuppression alone resulted in 47.8% KS complete remissions. Post-kidney transplantation KS is more frequent among males and patients of Middle Eastern and African origin. However, the gender difference may be attributed to most patients undergoing kidney transplants being male. Therefore, if gender balance is considered in future studies, then the difference might be insignificant. Based on our results, we can concur that the mainstay treatment for post-transplant KS is reduction or withdrawal of immunosuppression. However, the patients should be closely monitored to avoid KS recurrence and kidney rejection. Furthermore, there is an increased risk for KS with the use of cyclosporine-based immunosuppression. However, this does not mean that the withdrawal of this immunosuppression agent might result in improved KS outcomes because the withdrawal of azathioprine with or without cyclosporine reduction has also led to improved outcomes.

Interventions Performed in Children With Immunocompromised Conditions in the Pediatric Intensive Care Unit Within 48 Hours of Death.

Background: Understanding interventions preceding death in children with immunocompromised conditions is important to ensure a peaceful and dignified perideath experience. The aim of this study was to describe the number of interventions performed in the pediatric intensive care unit (PICU) within the 48 hours before death in this population. Methods: This was a single-center, retrospective cohort study of all children with an underlying oncologic, hematologic, or immunologic diagnosis admitted to the PICU for at least 72 hours between 2014 and 2021. Medical records were reviewed for interventions within 48 hours preceding death and for palliative care involvement. Interventions were defined as new or escalations in respiratory support, cardiopulmonary resuscitation (CPR), vascular access, drains, and radiographic studies. Associations were evaluated using simple logistic regression. Results: A total of 55 patients were included in this study. The predominant PICU admission diagnoses were respiratory (51%), followed by shock (25%), and neurologic diagnoses (9%). These predominant diagnoses were similar perideath. At PICU admission, only 1 patient had a do-not-resuscitate (DNR) order. Forty-six percent had a DNR order 48 hours preceding death, and 91% had DNR orders in place at time of death. During the 48-hour period preceding death, 80% of children received at least one intervention. Radiographic studies were the most common, used in 78% of children, followed by respiratory (20%), vascular (16%), CPR (13%), and drain placement (7%). Palliative care was involved in 38% of cases and was associated with a decrease in the number of radiologic interventions (p = 0.028) and CPR (p = 0.026). Conclusions: Children in the PICU with underlying immunocompromised conditions frequently receive interventions within the 48-hour period preceding death. Palliative care involvement was associated with fewer radiographic studies and fewer occurrences of CPR. The impact of interventions on the dying experience warrants further investigation.

Clinical and microbiological characteristics of Chryseobacterium indologenes bacteremia: A case report and review of literature

Chryseobacterium indologenes is an uncommon human pathogen that is aerobic, non-fermentative, and oxidase and indole positive. Its clinical relevance has yet to be fully determined. An increase in deadly infectious cases has been recorded in recent years, mostly in patients of older age group and immunocompromised states as a result of C. indologenes infection of medical equipment involving fluids and implanted devices. Because C. indologenes is resistant to the majority of antibiotics, therapy is challenging and this bacterium is thought to be an emerging cause of high mortality in critically ill patients. In our study, we describe a case of C. indologenes producing bacteremia in an elderly female patient with a history of ovarian cancer and hepatitis B infection who had underwent a right hemicolectomy with end ileostomy and a distal mucus fistula and was effectively treated with levofloxacin.

SPCS, a Novel Classifier System Based on Senescence Axis Regulators Reveals Tumor Microenvironment Heterogeneity and Guides Frontline Therapy for Clear Cell Renal Carcinoma

RationaleThe emerging evidence suggested that senescence regulator genes were involved in multi cancers, which may be utilized as new targets for cancers. However, the dysregulation and clinical impact of senescence regulator genes in clear cell renal cell cancer (ccRCC) were still in foggy. MethodsUsing multiomics data from TCGA-KIRC and other datasets, we comprehensively investigated the function of senescence regulator genes in ccRCC. ccRCC patients could be remodeled into 2 significant different groups basing on senescence regulators expression: senescence-pattern cancer subtype1 (SPCS1) and subtype2 (SPCS2). We further explored clinical characteristics, functional analysis, tumor immune microenvironment, immunotherapy response, genomic mutation and drug sensitivity between the 2 subtypes. Besides, senescence-pattern related risk model was established to determine the patient's prognosis of ccRCC. Finally, the overview of MECP2 function was investigated in multi cancers. ResultsccRCC patients could be divided into SPCS1 (normal aging group) and SPCS2 (Aging disorder group). The 2 subtypes showed significant different clinical characteristics and biological process in ccRCC. SPCS2, an aggressive subtype, comprised higher clinical stage and worse prognosis of ccRCC patients. SPCS2 subtype indicated activated oncogenic signaling pathway and metabolic signatures to prompt cancer expansion. SPCS2 subgroup owned immunocompromised status, which induced immune dysfunction and low ICI therapy response. The genome-copy numbers of SPCS2, including arm-gain and arm-loss was significantly more frequent than SPCS1. In addition, the 2 subtypes argue contrasting drug sensitivity profiles in clinical specimens and matched cell lines. Finally, we constructed a prognostic risk model consisted of each subtype's leading biomarkers, which exerted a satisfied performance for ccRCC patients. ConclusionSenescence regulator-related signature could modify functional pathways and tumor immune microenvironment by genome mutation and pathway interaction. Senescence regulator-related molecular subtype strengthen the understanding of ccRCC’ characterization and guide clinical treatment. Targeting senescence regulators may be regard as a proper way in ccRCC.

The IFSD Score-A Practical Prognostic Model for Invasive Fungal Spondylodiscitis.

Objectives: Invasive fungal spondylodiscitis (IFSD) is rare and could be lethal in certain circumstances. The previous literature revealed limited data concerning its outcomes. This study aimed to establish a risk-scoring system to predict the one-year mortality rate of this disease. Methods: A total of 53 patients from a multi-centered database in Taiwan were included in this study. All the clinicopathological and laboratory data were retrospectively analyzed. Variables strongly related to one-year mortality were identified using a multivariate Cox proportional hazards model. A receiver operating characteristic (ROC) curve was used to express the performance of our IFSD scoring model. Results: Five strong predictors were included in the IFSD score: predisposing immunocompromised state, the initial presentation of either radiculopathy or myelopathy, initial laboratory findings of WBC > 12.0 or <0.4 103/µL, hemoglobin < 8 g/dL, and evidence of candidemia. One-year mortality rates for patients with IFSD scores of 0, 1, 2, 3, and 4 were 0%, 16.7%, 56.3%, 72.7%, and 100%, respectively. The area under the curve of the ROC curve was 0.823. Conclusions: We developed a practical scoring model with easily obtained demographic, clinical, and laboratory parameters to predict the probability of one-year mortality in patients with IFSD. However, more large-scale and international validations would be necessary before this scoring model is commonly used.

Granulomatous myocarditis arising from intravesical Bacillus Calmette–Guérin therapy leading to death diagnosed by postmortem examination: a case report

BackgroundIntravesical Bacillus Calmette–Guérin (BCG) is used as a standard adjuvant therapy for non-muscle invasive urothelial cancer. Most patients tolerate the treatment well, with mild side effects. Systemic complications are extremely rare, occur due to BCG dissemination and are associated with immunocompromised state and urothelial breach.Case presentationWe present a case of a 78-year-old male, a former smoker, with history of non-muscle invasive urothelial carcinoma status post partial resection followed by intravesical BCG therapy. An autopsy was performed due to the sudden nature of his death. Autopsy showed multiple necrotizing granulomas in the brain, atrium, ventricles, lungs, kidneys, and urinary bladder. Stains for acid-fast bacilli and fungi were negative. In addition, bilateral lungs showed evidence of bronchopneumonia secondary to cytomegalovirus.ConclusionGranulomatous myocarditis arising from BCG therapy is extremely rare. Our patient with urothelial cancer treated with BCG developed multiorgan granulomas, most likely due to a hypersensitivity reaction to intravesical BCG. Arrhythmia induced by granulomatous myocarditis was the cause of his death. Although there have been few cases of systemic BCG-osis causing fatal sepsis leading to death, a cardiac cause of death is unique.

Deep neck space infections in end-stage renal disease patients: Prevalence and mortality.

Deep neck space infections (DNSI) are severe infections within the layers of neck fascia that are known to be associated with underlying immunocompromised states. Although uremia associated with kidney disease is known to cause immune system dysfunction, DNSI in patients with kidney disease has been poorly studied. This study investigated the prevalence of DNSI and the associated risk of mortality within the United States end-stage renal disease (ESRD) population, using a retrospective cohort study design and the United States Renal Data System database of patients (ages 18-100) who initiated dialysis therapy between 2005 and 2019. International Classification of Disease-9 and -10 codes were used to identify the diagnosis of DNSI and comorbid conditions. Of the 705,891 included patients, 2.2% had a diagnosis of DNSI. Variables associated with increased risk of DNSI were female sex, black compared to white race, catheter, or graft compared to arteriovenous fistula (AVF) access, autoimmune disease, chronic tonsillitis, diagnoses in the Charlson Comorbidity Index (CCI), tobacco use, and alcohol dependence. DNSI diagnosis was an independent risk factor for mortality, which was also associated with other comorbidity factors such as older age, catheter or graft compared to AVF access, comorbidities in the CCI, tobacco use, and alcohol dependence. Because of the increased mortality risk of DSNI in the ESRD population, health professionals should encourage good oral hygiene practices and smoking cessation, and they should closely monitor these patients to reduce poor outcomes.

Vaccinations in patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is characterized by immune dysfunction resulting in heightened susceptibility to infections and elevated rates of morbidity and mortality. A key strategy to mitigate infection-related complications has been immunization against common pathogens. However, the immunocompromised status of CLL patients poses challenges in eliciting an adequate humoral and cellular immune response to vaccination. Most CLL-directed therapy disproportionately impairs humoral immunity. Vaccine responsiveness also depends on the phase and type of immune response triggered by immunization. In this review, we discuss the immune dysfunction, vaccine responsiveness, and considerations for optimizing vaccine response in patients with CLL.

Holistic Care of the Immunocompromised Rheumatologic Patient – Case Analysis

Patients with rheumatologic conditions, such as eosinophilic granulomatosis with polyangiitis (EGPA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), often face being immunocompromised due to their disease state, or the immunosuppressive effect of their treatments. Managing immunocompromised rheumatologic patients can be challenging and complex. This article reviews a GSK-sponsored Innovation Theatre session that took place during the American College of Rheumatology (ACR) Convergence 2023 Annual Meeting in San Diego, California, USA, on 14th November 2023. Kevin Winthrop, Professor of Infectious Diseases at the School of Medicine at Oregon Health and Science University (OHSU); and Professor of Public Health at OHSU-Portland State University (PSU) School of Public Health, Portland, Oregon, USA, provided insights into the immunocompromised patient within rheumatology. He considered the challenges of associated comorbidities, diagnosis, and implementing preventative measures. Leonard Calabrese, Professor of Medicine at the Cleveland Clinic Lerner College of Medicine, Case Western Reserve University; Director of Clinical Immunology of the R.J. Fasenmyer Center; and Vice Chairman at the Department of Rheumatic &amp; Immunologic Disease, Cleveland Clinic, Ohio, USA, presented an interactive patient case overview of EGPA. He identified the need for practitioners to take ownership of patients with serious and opportunistic infections. The session provided awareness of the origins of immunocompromised states, including disease pathophysiology and treatments. It also explained the increased risks of opportunistic infections among patients with rheumatological conditions, due to their disease and treatment. Additionally, it identified the need for holistic approaches in the management of those patients living with immunocompromising conditions.

Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008–2020

BackgroundTransplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population.MethodsThis retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010–2012) and lower-disease burden (2016–2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation.ResultsOf 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7–0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7–4.2) and was the highest in children aged 0–19 years, at 9.0 (95% CI 5.7–13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis.ConclusionsTransplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.Graphical

P14 Study of Prescribing patterns and Effectiveness of Ceftolozane/Tazobactam Real-world Analysis (SPECTRA): results from a multinational, multicentre observational study

Abstract Background Ceftolozane/tazobactam (C/T) has demonstrated efficacy to treat complicated intra-abdominal infections (cIAI), complicated urinary tract infections (cUTI) and hospital acquired bacterial and ventilator-associated bacterial pneumonia. However, physicians, providers, and other stakeholders including payers want broader real-world evidence to inform clinical decisions and optimize healthcare resource use. Methods SPECTRA is a multinational, multicentre, retrospective, inpatient, observational study of patients treated with C/T in Australia, Austria, Germany, Italy, Mexico, Spain and the UK. Adult inpatients treated with ≥48 h of C/T were included. Demographics, clinical characteristics, treatment management patterns, and outcomes were analysed. Results There were 687 patients from 38 participating hospitals in 7 countries. The average age was 57.6 years (SD ±17.3), and most were male (456, 66.4%). The majority had at least one comorbidity (563, 82.0%), with the most common being heart disease (208, 30.3%), immunocompromised state (207, 30.1%) and chronic pulmonary disease (195, 28.4%). The most common indications were pneumonia (204, 29.7%), sepsis (147, 21.4%) and cIAI (106, 15.4%); 162 (23.6%) had multiple sites of infection and 245 (35.7%) were polymicrobial infections. Median C/T treatment was 12.0 days (IQR 11.0). Half of the patients were admitted to the ICU (343, 49.9%), 43.4% of which was related to the infection. Clinical success was 66.1%. All-cause in-hospital mortality was 22.0% with 8.7% being infection related. The 30 day all-cause readmission was 9.8% and 4.7% were infection related. Conclusions C/T was used to treat infections among critically ill patients and for multi-source, polymicrobial infections. Despite the complexity of the patients in this real-world analysis, most C/T patients had beneficial outcomes that are similar to results of controlled clinical trials.

Effects of plant-based heat killed lactic acid bacteria and its lithium chloride-extracted cellular protein on high-fat-induced obesity

The anti-obesity action of postbiotics derived from plant-based probiotics remains unclear. The effects of heat killed lactic acid bacteria (Lactobacillus plantarum, LPHK and Lactobacillus curvatus, LCHK) along with bioactive their cell envelop components known as surface layer proteins (SLPs, LPSLP, and LCSLP) on obesity were investigated. LPHK, LCHK, LPSLP, and LCSLP significantly reduced lipid accumulation in 3T3-L1 adipocytes, concurrently regulating the expression of adipogenic genes. Notably, LPHK demonstrated significant improvements in high-fat (HF)-induced body weight gain, adipose tissue weight gain, liver weight gain, and reduced plasma concentrations of triglyceride, total-cholesterol, and LDL-cholesterol in C57BL/6J mice. Additionally, LPHK significantly regulated the expression of genes related to adipogenesis and anti-apoptosis. Moreover, while LPSLP significantly reduced liver weight, plasma triglyceride and LDL-cholesterol concentrations, and upregulated genes associated with hepatic fatty acid oxidation, it did not affect the body weight and adipose tissue weight gain. These results suggest that additional components other than SLP are necessary for the anti-obesity action of LPHK. In conclusion, non-viable plant-based LPHK can be used as a naturally occurring product for preventing obesity, especially in individuals with immunocompromised conditions.

Rates of Lower Respiratory Tract Illness in US Adults by Age and Comorbidity Profile.

While it is widely recognized that older adults, adults with chronic medical conditions (CMC), and adults with immunocompromising conditions (IC) are at increased risk of lower respiratory tract illness (LRTI), evidence of the magnitude of increased risk is limited. This study was thus undertaken to characterize rates of hospitalized and ambulatory LRTI among United States (US) adults by age and comorbidity profile. A retrospective cohort design and US healthcare claims database (2016-2019) were employed. Study population included adults aged≥18years and was stratified by age and comorbidity profile (CMC-, CMC+, IC). LRTI was ascertained overall and by pathogen pathogen (e.g., respiratory syncytial virus [RSV]), and was classified by care setting (hospital, emergency department [ED], physician office/hospital outpatient [PO/HO]). Relative rates (RR) of LRTI generally increased with older age across care settings (vs. 18-49years), with the most marked increase for hospitalizations: for LRTI-hospitalized, RRs ranged from 3.3 for 50-64years to 46.6 for≥85years; for LRTI-ED and LRTI-PO/HO, RRs ranged from 1.0 to 2.7 and from 1.3 to 1.5, respectively. Within age groups, LRTI rates were also consistently higher among CMC+and IC adults (vs. CMC- adults). Age-specific RRs of LRTI patients hospitalized due to RSV were largely comparable to overall LRTI; age-specific RRs for other care settings, and RRs for CMC+and IC adults (vs. CMC- adults), were generally higher for LRTI due to RSV. Incidence of LRTI, including that due to RSV, especially for events requiring acute inpatient care, is markedly higher among older adults and adults of all ages with CMC or IC.