Risk Factors For Severe Infection Research Articles

When Chinese patients with plasma cell disorders encountered the nationwide Omicron outbreak (December 2022): a real-world multicenter and multiregional study.

This study aims to assess the impact of the nationwide Omicron outbreak in December 2022 on Chinese patients with plasma cell disorders (PCD), focusing on the clinical characteristics of PCD patients with COVID-19 and the risk factors contributing to adverse clinical courses (severity and hospitalization) and outcomes. A multicenter retrospective study was performed from December 1, 2022, to January 19, 2023. The study population includes 404 PCD patients, divided into a COVID-19 group (n = 342) and an uninfected group (n = 62). The frequency of COVID-19 infection was 84.7% (342/404), and 16.4% (56/342) were severe COVID-19. Among the 277 patients with complete follow-up, 2 deaths (0.7%) were reported, while 231 (83.4%) recovered from COVID-19. Age > 65 (P = 0.02) and prior anti-CD38 monoclonal antibody (mAb) treatment within six months (P = 0.03) were independent risk factors for severe infection. Additionally, previous chimeric antigen receptor T-cell (CAR-T) therapy within six months was correlated with a higher risk of hospitalization (P = 0.04) and prolonged recovery time (P = 0.03). No significant protective effect of vaccination on infection or severe infection was observed (P > 0.05). The latest Omicron outbreak results in higher rates of severe infection and mortality in PCD patients compared with the general population in China, highlighting the need to protect this vulnerable population during the pandemic. Recent use of anti-CD38 mAb and CAR-T therapy are associated with poorer clinical courses and outcomes of PCD patients with COVID-19.

Tumor Necrosis Factor Receptors and C-C Chemokine Receptor-2 Positive Cells Play an Important Role in the Intraerythrocytic Death and Clearance of Babesia microti.

Babesia microti is an Apicomplexan parasite that infects erythrocytes and causes the tick-transmitted infection, babesiosis. B. microti can cause a wide variety of clinical manifestations ranging from asymptomatic to severe infection and death. Some risk factors for severe disease are well-defined, an immune compromised state, age greater than 50, and asplenia. However, increasing cases of severe disease and hospitalization in otherwise healthy individuals suggests that there are unknown risk factors. The immunopathology of babesiosis is poorly described. CD4+ T cells and the spleen both play a critical role in parasite clearance, but few other factors have been found that significantly impact the course of disease. Here, we evaluated the role of several immune mediators in B. microti infection. Mice lacking TNF receptors 1 and 2, the receptors for TNFα and LTα, had a higher peak parasitemia, reduced parasite killing in infected red blood cells (iRBCs), and delayed parasite clearance compared to control mice. Mice lacking CCR2, a chemokine receptor involved in the recruitment of inflammatory monocytes, and mice lacking NADPH oxidase, which generates superoxide radicals, demonstrated reduced parasite killing but had little effect on the course of parasitemia. These results suggest that TNFR-mediated responses play an important role in limiting parasite growth, the death of parasites in iRBCs, and the clearance of iRBCs, and that the parasite killing in iRBCs is being primarily mediated by ROS and inflammatory monocytes/macrophages. By identifying factors involved in parasite killing and clearance, we can begin to identify additional risk factors for severe infection and newer therapeutic interventions.

The effects of age and frailty on the risks of end-stage renal disease, death, and severe infection in older adults with antineutrophil cytoplasmic antibody-associated vasculitis: a retrospective cohort study

Frailty, a measure of biological age, might predict poor outcomes in older adults better than chronological age. We aimed to compare the effect of age and frailty on end-stage renal disease, death, and severe infection within 2 years of diagnosis in older adults with incident antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. This retrospective cohort study included individuals aged 65 years or older from the Mass General Brigham ANCA-associated vasculitis cohort in the USA who were treated between Jan 1, 2002, and Dec 31, 2019. Individuals with a diagnosis of eosinophilic granulomatosis with polyangiitis were excluded from the analysis. Baseline frailty was measured with a claims-based frailty index using data collected in the year before the date of treatment initiation in individuals with at least one health-care encounter before baseline; individuals who did not have an encounter within the 12 months before baseline were classified as pre-frail. Incidence rates of end-stage renal disease or death and severe infections (ie, infections leading to hospital admission or death) at 2 years were estimated, and multivariable analyses were performed to compare the association of age and frailty with these outcomes. Cumulative incidence rates and an additive interaction analysis were used to assess the interaction of age and frailty groupings. Of the 234 individuals included, 136 (58%) were women, 98 (42%) were men, 198 (85%) were White, and 198 (85%) were positive for myeloperoxidase-specific ANCA. Frailty was present in 25 (22%) of 116 individuals aged 65-74 years and 44 (37%) of 118 aged 75 years or older. In the multivariable analysis, an age of 75 years or older was associated with an increased risk of end-stage renal disease or death (hazard ratio [HR] 4·50 [95% CI 1·83-11·09]), however, frailty was not (1·08 [0·50-2·36]). Both an age of 75 years or older (HR 2·52 [95% CI 1·26-5·04]) and frailty (8·46 [3·95-18·14]) were independent risk factors for severe infections. The effect of frailty on the incidence of end-stage renal disease or death was greater in individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 7·5 cases vs 2·0 cases per 100 person-years) than in those aged 75 years or older (13·5 cases vs 16·0 cases per 100 person-years). The effect of frailty on the incidence of serious infections varied by age, with large differences observed among both individuals aged 65-74 years (frail vs non-frail or pre-frail incidence rate 38·9 cases vs 0·8 cases per 100 person-years) and individuals aged 75 years or older (61·9 cases vs 12·3 cases per 100 person-years). Despite the observed differences between the age groups, the additive interaction terms were not statistically significant for either frailty and end-stage renal disease or death (p for interaction=0·276) or frailty and serious infections (p for interaction=0·650). Adults with ANCA-associated vasculitis aged 75 years or older had a higher incidence of end-stage renal disease, death, and severe infections within 2 years of diagnosis than adults aged 65-74 years. Frailty, an approximation of biological age, was a risk factor for severe infection. Assessment beyond chronological age could better inform management decisions in older adults with ANCA-associated vasculitis. National Institutes of Health and National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Changes in the epidemiological patterns of respiratory syncytial virus and human metapneumovirus infection among pediatric patients and their correlation with severe cases: a long-term retrospective study.

We aim to investigate the prevalence of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) among pediatric patients with acute respiratory tract illness (ARTI) in southern China both pre- and post-COVID-19 pandemic, as well as identify associated risk factors for severe infections. The study conducted a real-time PCR analysis on hospitalized children with ARTI from 2012 to 2023, specifically targeting RSV, hMPV, and other respiratory pathogens. Additionally, demographic data was collected during this analysis. The prevalence of RSV occurs triennially, and likewise, the temporal pattern of hMPV outbreaks mirrors that of RSV. The peak infection rates of RSV and hMPV occurred during and following the implementation of COVID-19 epidemic prevention and control measures. The incidence of RSV infection exhibited bimodal peaks in 2022, while hMPV demonstrated seasonal peaks during the spring, fall, and winter periods post-COVID-19 pandemic. After the COVID-19 outbreak, there has been an upward trend in the proportion of female patients and patients aged one year and older presenting with ARTI, RSV infections, and hMPV infections. Infant (OR = 4.767, 95%CI: [3.888-5.846], p < 0.0001), presence of co-infection (OR = 0.540, 95%CI: [0.404-0.722], p < 0.0001), and existence of comorbidities (OR = 1.582, 95%CI: [1.285-1.949], p < 0.0001) was the risk ratio for the severity of RSV infection. Children infected with hMPV under the age of 1 year (OR = 0.322, 95%CI: [0.180 - 0.575], p < 0.0001), as well as those with comorbidities (OR = 8.809, 95%CI: [4.493 - 17.272], p < 0.0001), have a higher risk of developing severe illness. The changing epidemiological patterns have the potential to lead to widespread severe outbreaks among children, particularly those with underlying medical conditions who may experience more severe symptoms. Conducting surveillance for pneumoviridae viruses in children is an imperative measure to establish a robust foundation for future epidemic prevention and treatment strategies.

Febrile young infants and the association with enterovirus infection

BackgroundEnterovirus is a common pediatric infectious disease, but the epidemiological data in young infants were lacking. This study aims to evaluate the role of enterovirus in febrile young infants and identify risk factors for severe infections. MethodsWe enrolled febrile infants younger than 90 days admitted to National Taiwan University Hospital from January 2010 to June 2021. Enterovirus infection was confirmed via viral isolation or pan-enterovirus PCR. Central nervous system involvement was defined by positive culture or PCR in cerebrospinal fluid. Severe complications included sepsis, hepatic failure, myocarditis, shock, encephalitis, acute kidney injury, respiratory failure, and multiorgan failure. ResultsOut of 840 febrile infants, 17.4% (n = 146) had enterovirus infection. Among these, 46% (n = 67) presented with meningitis and/or encephalitis. Early-onset enterovirus infection within the first two weeks of life was significantly linked to increased risks of anemia (hemoglobin <9 g/dL), ICU admission, central nervous system involvement, shock, hepatic failure, and mortality. Multivariable logistic regression identified high-risk serotypes (aOR 17.4, [95% CI 1.58, 191.5], p = 0.019) and hemoglobin <9 g/dL (aOR 44.9, [95% CI 5.6, 357.6], p < 0.001) as significant risk factors for severe complications. ConclusionsEnterovirus accounted for 17.4% of the etiology in febrile young infants and the case-fatality rate was 2%. Febrile young infants who had risk factors of enterovirus infection should consider viral culture or PCR examination for confirmation.

Investigation of infections status in pediatric patients with acute myeloid leukemia during the induction period-a retrospective study in two medical centers.

This study aims to investigate the clinical characteristics of infections following induction chemotherapy for acute myeloid leukemia (AML) in children and identify risk factors associated with severe infections. Newly diagnosed children with AML treated at the Hematology Oncology Center of Beijing Children's Hospital affiliated to Capital Medical University (referred to as the "Beijing ward") and Baoding Hospital of Beijing Children's Hospital (referred to as the "Baoding ward") between November 2019 and August 2022 were enrolled. The diagnosis and treatment of the patients were carried out in accordance with the CCLG-AML 2019 protocol. Their essential information and infection-related indicators were collected. The various indicators between the two centers were compared. The incidence of infection in children with AML was 100%, with a severe infection rate of 15.3% and an infection-related mortality rate of 2.4%. Respiratory infections accounted for 39.7% of all infections events, and unspecified site infection for 32.2%. Bacterial infections were predominant at 51.2%. The bed unit area (BUA) varied significantly with 4.1 m2 in the Beijing ward and 10 m2 in the Baoding ward. Significant differences were observed in gastrointestinal infections (P < 0.001) and severe infections (P = 0.014) between the two wards. Several factors were identified as risk factors for severe infections, including BUA difference (OR = 4.353, 95% CI: 1.078-17.578), time of entering neutropenia phase after chemotherapy (OR = 6.369, 95% CI: 1.713-23.675) and bloodstream infection (OR = 7.466, 95% CI: 1.889-29.507). Respiratory tract infections and infections of unspecified site are most common during induction phase for pediatric AML. Bacteria, especially G- bacteria, are the leading pathogens. Risk factors for severe infections include a small BUA, entering neutropenia phase ≤ 5.5days after chemotherapy, and bloodstream infection. Recognizing these risk factors can aid in the early identification and intervention of severe infections.

More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Beijing remain elusive. SARS-CoV-2-positive children admitted to the intensive care unit (ICU) with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis-based multiplex PCR from December 12, 2022, to January 24, 2023. The SARS-CoV-2 sub-variants were identified using next-generation sequencing. Plasma was positive for two (positive; P), one (suspicious; S), or no (negative; N) SARS-CoV-2 genes were classified as plasmatic RNA-positive (RNAemia; P + S) or without RNAemia (N). Clinical and laboratory data of the enrolled cases were then collected and analyzed. The 34 enrolled children included 26 males and 24 younger than three years. All were negative for other respiratory pathogens. BF.7.14 (18/29) was the predominant subvariant. Viral loads in respiratory specimens, hours from symptom onset to the first respiratory specimen collection (time-variable), with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs. N and RNAemia vs. without RNAemia group. Among most cases, the T lymphocyte ratios decreased, while the cytokine level and the B lymphocyte ratio increased. The time variables were 2.22 ± 2.05 and 4.00 ± 2.49 days in BF.7.14 and BA.5.2 infections, respectively. In conclusion, SARS-CoV-2 was more likely to cause severe infections among males aged ≤ 3 years old with comorbidities during the SARS-CoV-2 outbreak in Beijing, while RNAemia is more common in children at the early stage of severe BF.7.14 infections, and most had high cytokine levels and B-cell activation.

Molecular characterisation of Staphylococcus aureus in school-age children in Guangzhou: associations among agr types, virulence genes, sequence types, and antibiotic resistant phenotypes

BackgroundStaphylococcus aureus, one of the most prevalent opportunistic pathogens, mainly colonizes the nasal cavity and is a risk factor for severe infections. Virulence factors and accessory gene regulator (agr) are key to the severity and diversity of staphylococcal infection. In this study, we aimed to characterise S. aureus agr-types and virulence genes and correlated them with genetic background and antibiotic-resistant phenotypes.ResultsAgr types were identified in 704 isolates (98.5%), with only 11 isolates were negative for agr type. Most of our isolates were classified as agr type I, followed by types III, II and IV. The enterotoxin c gene (sec) was detected in 48.6% of isolates, showing the highest prevalence among the five enterotoxin genes detected. The positivity rates for the lukS/F-PV and tsst genes were 4% and 2.2%, respectively, while neither sed nor SasX were detected. ST45, ST59, ST338, ST188, ST6, ST7, ST22, ST25, ST398, and ST944 belonged to agr I group, while ST5 and ST15 belonged to agr II group. ST30 and ST1 were classified into agr III group, and ST121 was assigned into agr IV group. The tsst gene was found exclusively within agr I and III types belonging to ST7 and ST30 isolates, while the lukS/F-PV was predominantly carried by agr I type isolates primarily within CC59 and CC22 clones. Among the methicillin-resistant S. aureus (MRSA) isolates, 89.7% belonged to agr I group, and 97.8% of rifampicin-resistant or intermediate isolates were assigned to agr I group. MRSA isolates harboured more tested virulence genes compared to methicillin-susceptible S. aureus isolates.ConclusionsWe characterized the distributions of agr types and eight major virulence genes of 715 S. aureus isolates, and our findings revealed clear associations between agr types and STs, as well as virulence genes, and drug resistant phenotypes.

Risk Factors for Severe Infection and Unfavorable Outcomes in Hematologic Malignancy Patients with COVID-19 Inflection during the Omicron Era: A Chinese Single-Center Retrospective Study

Purpose: The objective of this study was to evaluate the potential risk factors associated with severe infection and unfavorable outcomes among individuals with hematologic malignancies who contracted the coronavirus infectious disease (COVID-19) during the Omicron era. Methods: This retrospective analysis included adult patients with hematologic malignancies who were diagnosed with COVID-19 during the period from November 2022 to February 2023. A comparison was made between the clinical characteristics of patients who experienced persistent COVID-19 infection or succumbed to death within 30 days and those of the remaining patients. Results: A total of 134 patients were included in the analysis, with 23.9% (n=32) presenting as asymptomatic/mild and 29.1% (n=39) classified as severe cases. Among the patients, 54.4% (n=73) had received at least two doses of vaccines. In the subgroup of asymptomatic/mild patients, 50% had received at least three doses of vaccines, while among the severe patients, 56.4% remained unvaccinated. The multivariate analysis examining risk factors for severe infection in COVID-19 and hematologic malignancy patients identified the number of vaccine doses as an independent prognostic factor. Less than two doses of vaccines were found to be associated with severe COVID-19 infection (odds ratio [OR]: 4.213, 95% confidence interval [CI] 1.433-12.392; p=0.009). In this study, patients with persistent COVID-19 infection or succumbed to death within 30 days were categorized as the unfavorable group (n=57), while the remaining patients were classified as the favorable group (n=77). A significant difference was observed between the two groups in terms of median age (p=0.015), malignancy status (p=0.001), number of vaccine doses received (p=0.001), neutrophil count (p=0.011), immunoglobulin G levels (p=0.038), and interleukin-6 levels (p=0.025). In the multivariable analysis of risk factors for unfavorable outcomes in patients with both COVID-19 and hematologic malignancies, it was found that the number of vaccine doses and the level of immunoglobulin G were independent prognostic factors. Specifically, receiving less than two doses of vaccines (OR: 233, 95%CI 0.068-0.798; p=0.020) and having an immunoglobulin G level below 1000 (OR: 220, 95%CI 0.066-0.753; p=0.014) were associated with unfavorable outcomes. Conclusions: Receiving multiple doses of vaccines and having higher levels of immunoglobulin G were found to improve the clinical outcome of COVID-19 in patients with hematologic malignancies.

Cough and sputum in long COVID are associated with severe acute COVID-19: a Japanese cohort study

BackgroundMultiple prolonged symptoms are observed in patients who recover from acute coronavirus disease 2019 (COVID-19), defined as long COVID. Cough and sputum are presented by patients with long COVID during the acute and post-acute phases. This study aimed to identify specific risk factors for cough and sputum in patients with long COVID.MethodsHospitalized patients with COVID-19 aged 18 years were enrolled in a multicenter cohort study at 26 medical institutions. Clinical data during hospitalization and patient-reported outcomes after discharge were collected from medical records, paper-based questionnaires, and smartphone apps.ResultsAt the 3-, 6-, and 12-month follow-ups, there were no differences in the incidence rates of wet and dry coughs. In contrast, the proportion of patients presenting sputum without coughing increased over time compared to those with sputum and coughing. Univariate analyses of cough and sputum at all follow-up visits identified intermittent mandatory ventilation (IMV), smoking, and older age as risk factors for prolonged symptoms. At the 12-month follow-up, persistent cough and sputum were associated with the characteristics of severe COVID-19 based on imaging findings, renal and liver dysfunction, pulmonary thromboembolism, and higher serum levels of LDH, KL-6, and HbA1C. The Kaplan–Meier curves showed that the severity of acute COVID-19 infection was correlated with prolonged cough and sputum production. Multivariable logistic regression analysis showed that IMV ventilator management were independent risk factors for prolonged cough and sputum at 12 months.ConclusionsIn a Japanese population with long COVID, prolonged cough and sputum production were closely associated with severe COVID-19. These findings emphasize that a preventive approach including appropriate vaccination and contact precaution and further development of therapeutic drugs for COVID-19 are highly recommended for patients with risk factors for severe infection to avoid persistent respiratory symptoms.

Clinical characteristics and risk factors of acute lymphoblastic leukemia in children with severe infection during maintenance treatment.

Infection is the most common adverse event of acute lymphoblastic leukemia (ALL) treatment and is also one of the main causes of death. To investigate the clinical characteristics and risk factors of severe infections during the maintenance phase of ALL treatment, we conducted a retrospective study. A total of 181 children were eligible and 46 patients (25.4%) suffered from 51 events of severe infection, most of which occurred in the first half year of the maintenance phase (52.9%). The most common infection was pulmonary infection (86.3%) followed by bloodstream infection (19.6%). The main symptoms of ALL patients with pulmonary infection were fever, cough, and shortness of breath. The main manifestations of computer tomography (CT) were ground glass shadow (56.8%), consolidation shadow (27.3%), and streak shadow (25%). Multivariate binary logistic regression analysis showed that agranulocytosis, agranulocytosis ≥7 days, anemia, and low globulin level were independent risk factors for severe infection during the maintenance phase (all p < 0.05). Taken together, blood routine examinations and protein levels should be monitored regularly for ALL patients in the maintenance phase, especially in the first 6 months. For ALL patients with risk factors, preventive anti-infective or supportive therapies can be given as appropriate to reduce the occurrence of severe infections.

Lymphopenia is a risk factor for severe infections in older patients with microscopic polyangiitis: a retrospective cohort study in Japan.

Previous studies have identified the predictors of severe infections in ANCA-associated vasculitis. However, lymphopenia has not been fully evaluated as a predictor of subsequent severe infections in patients with microscopic polyangiitis (MPA). The aim of this study was to assess the association between lymphopenia and severe infections requiring hospitalization after receiving immunosuppressive therapy for MPA. This single-centre retrospective cohort study included 130 consecutive patients with newly diagnosed MPA from Aichi Medical University Hospital, Japan, who received immunosuppressive therapy between March 2004 and December 2020. The relationship between lymphopenia and subsequent severe infections was assessed using time-dependent multivariate Cox proportional hazard models adjusted for clinically relevant factors. During the follow-up period (median: 38 months; interquartile range: 15-63 months), 56 severe infectious episodes occurred in 51 patients (39.2%). Time-dependent multivariate Cox proportional hazard analyses identified older age [adjusted hazard ratio (HR) = 1.74 per 10 years, 95% CI: 1.13, 2.67], methylprednisolone pulse therapy (adjusted HR = 2.04, 95% CI: 1.03, 4.02), moderate lymphopenia (vs normal, adjusted HR = 7.17, 95% CI: 3.10, 16.6) and severe lymphopenia (vs normal, adjusted HR = 36.1, 95% CI: 11.8, 110.9) as significant predictors of severe infection. Lymphopenia is a predictor of subsequent severe infections in patients with MPA who receive immunosuppressive therapy. These results suggest the importance of sustained infection surveillance, particularly in older patients who develop lymphopenia during strong immunosuppressive therapy.

Incidence of and risk factors for suspected COVID-19 reinfection in Kyoto City: a population-based epidemiological study.

To determine the clinical characteristics of and risk factors for suspected reinfection with coronavirus 2019 (COVID-19). This was a retrospective cohort study using population-based notification records of residents in Kyoto City (1.4 M) with laboratory-confirmed COVID-19 infection between 1 March 2020 and 15 April 2022. Reinfection was defined by two or more positive COVID-19 test results ≧ 90 days apart. Demographic characteristics, the route and timing of infection and history of vaccination were analysed to identify risk factors for reinfection. Among the cohort of 107,475 patients, reinfection was identified in 0.66% (n = 709). The age group with the highest reinfection rate was 18-39 years (1.06%), followed by 40-59 years (0.58%). Compared to the medical and nursing professionals, individuals who worked in the construction and manufacturing industry (odds ratio [OR]: 2.86; 95% confidence interval [CI]: 1.66-4.92) and hospitality industry (OR: 2.05; 95% CI: 1.28-.31) were more likely to be reinfected. Symptomatic cases at initial infection, receiving more than 2 doses of vaccination and risk factors for severe infection at initial infection were protective factors against reinfection. Of the reinfected individuals, the reinfection route was unknown in 65%. Reinfection with COVID-19 is uncommon, with suspected reinfections more likely in adults, those with high exposure and unvaccinated individuals; the reinfection route was unknown in the majority of cases. This study confirmed the need to continue with self-protection efforts and to implement vaccination programs in high-risk populations.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Infections lead to mortality in up to 50% of patients (pts) with chronic lymphocytic leukemia (CLL). Immunoglobulin G (IgG) testing detects hypogammaglobulinemia (HGG; <500 mg/dL), a secondary immunodeficiency and risk factor for severe infections (SI) in pts with CLL. We hypothesized that increased IgG testing is associated with improved identification of HGG and reduced risk of SI in CLL. Methods: This retrospective study used de-identified patient data (structured data only) from the Mass General Brigham Research Registry. Eligible adults with CLL (diagnosed post-2010) had ≥12 months of clinical data and ≥3 visits/year. IgG levels and rates of HGG and SI pre- and post-immunoglobulin replacement therapy (IgRT) were compared. A multivariable logistic regression model examined the association of SI with IgG testing, controlling for IgRT, HGG, treatment, age, and sex. Results: Of 2842 pts with CLL and median (IQR) follow-up of 4.2 (2.2, 6.8) years, 1352 (47.6%) underwent IgG testing; 464 (34.3%) had HGG; 179 (6.3%) received IgRT; and 75.2% were treatment-naive. IgRT use (median [IQR] administrations of 2.0 [1.0, 4.0]) increased IgG levels (502.0 mg/dL [397.0, 615.0] vs. 367.0 mg/dL [245.0, 454.0]) and reduced rates of HGG (38.0% vs. 80.3%, p < 0.0001) and SI (33.7% vs. 51.0%, P=0.003) in the 12 months post-IgRT. IgG testing and IgRT use were independently associated with a significantly lower SI risk (Table). Pts with ≥3 versus 1-2 IgG tests were more likely to be identified with HGG (51.5% [321/623] vs. 19.6% [143/729], p < 0.0001), and pts with HGG who had ≥3 IgG tests were more likely to receive IgRT (32.7% [105/321] vs. 13.3% [19/143], p < 0.0001). Conclusions: Increased IgG testing was independently associated with lower risk of SI. Greater HGG risk awareness and more standardized IgG testing might reduce SI in pts with CLL. Study/writing support funder: Takeda Pharmaceuticals USA, Inc. Keywords: chronic lymphocytic leukemia (CLL), immunotherapy, late effects in lymphoma survivors The research was funded by: Analysis Group, Inc. conducted this study in collaboration with Takeda Pharmaceuticals USA, Inc. Under the direction of the authors, medical writing services were provided by Oxford PharmaGenesis Inc., and were funded by Takeda Pharmaceuticals USA, Inc. Conflict of interest: J. D. Soumerai Consultant or advisory role: Abbvie, AstraZeneca, Beigene, Bristol Myers Squibb, Roche, Seattle Genetics, TG Therapeutics, and Verastem Research funding: Adaptive Biotechnologies, Beigene, BostonGene, Genentech/Roche, GlaxoSmithKline, Moderna, Takeda, and TG Therapeutics Z. Yousif Employment or leadership position: Takeda Pharmaceuticals USA, Inc. and the University of California, San Diego. T. Gift Employment or leadership position: Takeda Pharmaceuticals USA, Inc. Stock ownership: Takeda R. Desai Employment or leadership position: Analysis Group, Inc. Analysis Group, Inc. Research funding: Takeda Pharmaceuticals L. Huynh Employment or leadership position: Analysis Group, Inc Research funding: Takeda Pharmaceuticals M. S. Duh Employment or leadership position: Analysis Group, Inc Research funding: Takeda Pharmaceuticals M. E. Sanchirico Employment or leadership position: Takeda Pharmaceuticals USA, Inc. Stock ownership: Takeda

Consensus document on the management of febrile neutropenia in paediatric haematology and oncology patients of the Spanish Society of Pediatric Infectious Diseases (SEIP) and the Spanish Society of Pediatric Hematology and Oncology (SEHOP)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient’s characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance.The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

Documento de consenso de manejo de neutropenia febril en el paciente pediátrico oncohematológico de la Sociedad Española de Infectología Pediátrica (SEIP) y la Sociedad Española de Hematología y Oncología Pediátrica (SEHOP)

Febrile neutropenia is one of the main infectious complications experienced by paediatric patients with blood or solid tumours, which, despite the advances in diagnosis and treatment, are still associated with a significant morbidity and mortality. These patients have several risk factors for infection, chief of which are chemotherapy-induced neutropenia, the disruption of cutaneous and mucosal barriers and the use of intravascular devices. Early diagnosis and treatment of febrile neutropenia episodes based on the patient's characteristics is essential in patients with blood and solid tumours to improve their outcomes. Therefore, it is important to develop protocols in order to optimise and standardise its management. In addition, the rational use of antibiotics, with careful adjustment of the duration of treatment and antimicrobial spectrum, is crucial to address the increase in antimicrobial drug resistance.The aim of this document, developed jointly by the Spanish Society of Pediatric Infectious Diseases and the Spanish Society of Pediatric Hematology and Oncology, is to provide consensus recommendations for the management of febrile neutropenia in paediatric oncology and haematology patients, including the initial evaluation, the stepwise approach to its treatment, supportive care and invasive fungal infection, which each facility then needs to adapt to the characteristics of its patients and local epidemiological trends.

Patterns of IgG Testing and Rates of Hypogammaglobulinemia in Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

BackgroundInfections cause substantial morbidity and up to 50% of deaths in patients with chronic lymphocytic leukemia (CLL). Hypogammaglobulinemia (HGG), a reversible risk factor for severe infections, is associated with CLL and its therapies. We evaluated patterns of immunoglobulin G (IgG) testing and immunoglobulin replacement therapy (IgRT) initiation in patients with CLL. MethodsThis retrospective, longitudinal study evaluated the real-world use of IgG testing in adults with CLL diagnosed after 2010 using deidentified clinical data from the Massachusetts General Brigham Research Patient Data Registry. Eligible patients had ≥12 months of clinical information post-CLL diagnosis and ≥3 visits/year. Timing of IgG testing, IgRT initiation, and serum IgG levels before and after IgRT initiation were examined. Results were reported with descriptive statistics including medians and interquartile range (IQR); P-values were calculated using McNemar’s test. ResultsThe cohort included 2842 patients; median (IQR) age was 69 (60, 76) years, 61.3% were men, 92.9% were White, 75.2% were treatment-naïve, and median (IQR) follow-up was 4.2 (2.2, 6.8) years. Of 1352 (47.6%) patients with IgG testing during the follow-up period, median (IQR) number of IgG tests was 0.5 (0.2,1.2) per patient/year; 34.1% had HGG (IgG < 500 mg/dL). Median (IQR) time from CLL diagnosis to first IgG test was 6.9 (0.9, 22.6) months. Number of IgG tests, IgRT administrations, timing of IgRT initiation from diagnosis and IgG testing, and serum IgG levels before and after IgRT initiation are described in the Table. Among patients with ≥1 IgRT administration, median (IQR) IgG serum levels improved and the proportion of patients with HGG decreased ≥12 months following IgRT initiation (Table). ConclusionsAs CLL treatment evolves, it is important to identify which patients are at greatest risk of infections and to standardize HGG screening. This study demonstrates that IgG levels are not assessed frequently post-CLL diagnosis, nor uniformly reassessed following initiation of IgRT. Among patients with CLL receiving IgRT, IgG levels improved after IgRT initiation. Thus, increased awareness and IgG screening might reduce severe or recurrent infections in the CLL patient population.Takeda Pharmaceuticals USA, Inc. funded the study and writing support.

Severe infections in patients with systemic lupus erythematosus from Tunisia: Prevalence and risk factors.

Since the improvement in management and the reduction of mortality caused by the disease activity, infections have represented the main cause of morbidity and mortality in systemic lupus erythematosus patients. We aimed to determine the prevalence and identify risk factors of severe infections in systemic lupus erythematosus patients. We conducted a retrospective study on 93 Tunisian lupus patients followed between 2010 and 2019. The mean age of the disease was 33.63 ± 13.76years. Fifty-two patients had 118 infections and 16% of the infections were serious. The bivariate analysis revealed a positive correlation between the total cumulative doses of corticosteroids and the number of serious infections (p = 0.009). The multivariate study has shown that the number of flares (p = 0.03), pulmonary manifestations (p = 0.01), pleuritis (p = 0.001), and the total cumulative dose of corticosteroids (p = 0.04) were independent risk factors of severe infections (p < 0.001). The use of antimalarials exerted a protective effect from severe infection [OR = 0.19 (95% CI 0.03-0.9)] p < 0.03.

Severe Infections in Patients Treated with Tocilizumab for Systemic Diseases Other Than Rheumatoid Arthritis: A Retrospective Multicenter Observational Study.

This study aimed to describe severe infections in patients treated with tocilizumab for systemic diseases other than rheumatoid arthritis. Data from patients receiving at least 2 doses of tocilizumab for systemic diseases other than rheumatoid arthritis between January 1, 2012, and July 1, 2020, in the region Poitou-Charentes (France) were retrospectively collected from medical records. Psoriatic arthritis and systemic juvenile idiopathic arthritis were also excluded as usually treated with similar modalities to rheumatoid arthritis. Of 37 patients, mainly suffering from giant cell arteritis, 25 patients (68%) had at least 1 infectious event and 15 severe infections occurred in 6 patients (3.2/100 patient-years), mainly bacterial. Lower respiratory tract and skin were the main sites. Severe bacterial infections were associated with a marked biological inflammatory syndrome, even under a cycle of administration of tocilizumab. Two severe zonas and 1 severe diverticulitis occurred. No tuberculosis or viral hepatitis reactivation was observed. The incidence rate of severe infections was 3.2/100 patient-years and seems lower than that reported in rheumatoid arthritis. C-reactive protein dosage could be helpful for the diagnosis of bacterial infectious adverse events in patients on tocilizumab. Further larger studies are needed to confirm these results to assess potential risk factors for severe infections.

The syndromic triad of COVID-19, type 2 diabetes, and malnutrition.

The coronavirus disease 2019 (COVID-19) pandemic challenges our collective understanding of transmission, prevention, complications, and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Risk factors for severe infection, morbidity, and mortality are associated with age, environment, socioeconomic status, comorbidities, and interventional timing. Clinical investigations report an intriguing association of COVID-19 with diabetes mellitus and malnutrition but incompletely describe the triphasic relationship, its mechanistic pathways, and potential therapeutic approaches to address each malady and their underlying metabolic disorders. This narrative review highlights common chronic disease states that interact epidemiologically and mechanistically with the COVID-19 to create a syndromic phenotype-the COVID-Related Cardiometabolic Syndrome-linking cardiometabolic-based chronic disease drivers with pre-, acute, and chronic/post-COVID-19 disease stages. Since the association of nutritional disorders with COVID-19 and cardiometabolic risk factors is well established, a syndromic triad of COVID-19, type 2 diabetes, and malnutrition is hypothesized that can direct, inform, and optimize care. In this review, each of the three edges of this network is uniquely summarized, nutritional therapies discussed, and a structure for early preventive care proposed. Concerted efforts to identify malnutrition in patients with COVID-19 and elevated metabolic risks are needed and can be followed by improved dietary management while simultaneously addressing dysglycemia-based chronic disease and malnutrition-based chronic disease.