Higher Risk Of Serious Infections Research Articles

Rates of severe neutropenia and infection risk in patients treated with deferiprone: 28 years of data

AbstractPatients treated with deferiprone for transfusional iron overload may experience idiosyncratic drug–induced neutropenia (IDIN) that may increase risk of infection. This analysis examined the rates of severe IDIN and risk of serious infections at different absolute neutrophil count (ANC) levels during deferiprone treatment. Events of severe IDIN (ANC <0.5 × 109/L) and associated serious infections from clinical trials and postmarketing setting were analyzed by discrete ANC levels: group 1, 0.2 × 109/L to 0.5 × 109/L; group 2, 0.1 × 109/L to 0.199 × 109/L; group 3, <0.1 × 109/L. In clinical trials, 22 events of severe IDIN occurred (group 1, n = 9; group 2, n = 3; group 3, n = 10), and rates of severe IDIN per 100 patient-years were 0.45 in group 1; 0.15 in group 2; and 0.50 in group 3 (1990.26 patient-years deferiprone exposure). All serious infections were in group 3 (3/10 [30.0%]). In the postmarketing setting, 176 events of severe IDIN were reported (group 1, n = 65; group 2, n = 20; group 3, n = 91) and rates of severe IDIN per 100 patient-years were 0.06 in group 1; 0.02 in group 2; and 0.08 in group 3 (111 570.24 patient-years deferiprone exposure). Rates of serious infection were 7.7% (5/65) in group 1; 10% (2/20) in group 2; and 13.2% (12/91) in group 3. Our findings suggest a high risk of serious infections with ANC <0.2 × 109/L during deferiprone treatment, a level consistent with the recent neutropenia guidelines.

Preterm Birth and in Utero Exposure to Corticosteroids Are Associated With Increased Infection Risk in Children of Mothers With IBD.

Corticosteroids, thiopurines, and biologics may come into play during pregnancy in women with inflammatory bowel disease and potentially impact the developing fetal immune system. We aimed to assess the risk of serious infections in children stratified by in utero exposure to biologics and immunomodulators or concomitant treatment with corticosteroids. All singleton IBD pregnancies between 2008 and 2022 at a tertiary IBD center in Denmark were included. Maternal and offspring demographics, maternal disease activity, antenatal medical treatment, and infant infections resulting in hospital admission were recorded after review of medical records. In 602 live births (99.0%), we registered exposure to antenatal treatment as follows: biological monotherapy (n = 61, 10.2%), thiopurines (n = 110, 17.9%), biologics and concomitant thiopurines (n = 63, 10.3%), and controls (ie, no treatment with biological and/or thiopurines; n = 369, 60.6%). Preterm delivery (<37 gestational weeks) and systemic steroid administration during the third trimester were associated with an increased risk of serious infection in the offspring immediately after birth (relative risk = 17.5; 95% confidence interval, 7.8-39.8; P < .001, and relative risk = 4.8; 95% confidence interval, 1.5-12.7; P = 0.003, respectively).Intra-uterine exposure to biologics or combination treatment were not associated with a statistically significant higher risk of serious infections compared with controls; however, combination treatment showed an inclination towards an increased risk across analyses. Preterm birth and systemic corticosteroid administration late in pregnancy are significant risk factors for serious infections in the offspring of IBD mothers.

Comparisons of infection events associated with tumor necrosis factor inhibitors in patients with inflammatory arthritis: A systematic review and network meta-analysis.

Objective: To compare the risk of infection in inflammatory arthritis patients treated with tumor necrosis factor (TNF) inhibitors. Methods: PubMed, Embase, and the Cochrane Library were systematically searched from inception to 28 December 2023 for randomized controlled trials (RCTs) assessing TNF inhibitors and reporting infections. Subsequently, pairwise and network meta-analyses were conducted to determine odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Results: A total of 61 RCTs involving 20,458 patients were included. Pairwise meta-analysis revealed that certolizumab pegol was significantly associated with an increased risk of serious infection compared to placebo (OR:2.28, 95% CI: 1.13-4.62). Both adalimumab and certolizumab pegol were also significantly associated with an increased risk of any infection compared to placebo (OR:1.18, 95% CI: 1.06 to 1.30 and OR:1.40, 95% CI: 1.11 to 1.76, respectively). Moreover, a network meta-analysis indicated that certolizumab pegol and infliximab were associated with a higher risk of serious infection compared to other TNF inhibitors. In the cumulative ranking of any infection risk, certolizumab pegol had the highest risk compared with others. TNF inhibitors increased the risk of tuberculosis but not that of herpes zoster. Conclusion: Available evidence indicates etanercept and golimumab are likely associated with a lower risk of infection compared to other TNF inhibitors in inflammatory arthritis. For patients at a heightened risk of infection, prioritizing the use of etanercept and golimumab may be advisable to minimize patient risk. Systematic Review Registration: identifier CRD42022316577.

What benefit–risk trade-offs are acceptable to rheumatoid arthritis patients during treatment selection? Evidence from a multicountry choice experiment

ObjectiveUnderstanding preferences of patients with rheumatoid arthritis (RA) can facilitate tailored patient-centric care. This study elicited trade-offs that patients with RA were willing to make during treatment selection.MethodsPatients with RA...

Presence of MDSC associates with impaired antigen-specific T cell reactivity following COVID-19 vaccination in cirrhotic patients.

Cirrhosis entails high risk of serious infections and abated efficiency of vaccination, but the underlying mechanisms are only partially understood. This study aimed at characterizing innate and adaptive immune functions, including antigen-specific T cell responses to COVID-19 vaccination, in patients with compensated and decompensated cirrhosis. Immune phenotype and function in peripheral blood from 42 cirrhotic patients and 44 age-matched healthy controls were analysed after two doses of the mRNA-based COVID-19 vaccines [BNT162b2 (Pfizer BioNTech) or mRNA-1273 (Moderna)]. Cirrhotic patients showed significantly reduced blood counts of antigen-presenting dendritic cells (DC) and high counts of monocytic myeloid-derived suppressor cells (M-MDSC) as compared to healthy controls. In addition, monocytic cells recovered from cirrhotic patients showed impaired expression of the antigen-presenting molecule HLA-DR and the co-stimulatory molecule CD86 upon Toll-like receptor (TLR) stimulation. These features were more prominent in patients with decompensated cirrhosis (Child-Pugh classes B & C). Interestingly, while patients with compensated cirrhosis (Child-Pugh class A) showed an inflammatory profile with myeloid cells producing the proinflammatory cytokines IL-6 and TNF, decompensated patients produced reduced levels of these cytokines. Cirrhotic patients, in particular those with more advanced end-stage liver disease, mounted reduced antigen-specific T cell reactivity to COVID-19 vaccination. Vaccine efficiency inversely correlated with levels of M-MDSC. These results implicate MDSC as mediators of immunosuppression, with ensuing deficiency of vaccine-specific T cell responses, in cirrhosis.

Patient Preference Trade-offs for Next-Generation Kidney Replacement Therapies.

Next-generation implantable and wearable KRTs may revolutionize the lives of patients undergoing dialysis by providing more frequent and/or prolonged therapy along with greater mobility compared with in-center hemodialysis. Medical device innovators would benefit from patient input to inform product design and development. Our objective was to determine key risk/benefit considerations for patients with kidney failure and test how these trade-offs could drive patient treatment choices. We developed a choice-based conjoint discrete choice instrument and surveyed 498 patients with kidney failure. The choice-based conjoint instrument consisted of nine attributes of risk and benefit pertinent across KRT modalities. Attributes were derived from literature reviews, patient/clinician interviews, and pilot testing. The risk attributes were serious infection, death within 5 years, permanent device failure, surgical requirements, and follow-up requirements. The benefit attributes were fewer diet restrictions, improved mobility, pill burden, and fatigue. We created a random, full-profile, balanced overlap design with 14 choice pairs plus five fixed tasks to test validity. We used a mixed-effects regression model with attribute levels as independent predictor variables and choice decisions as dependent variables. All variables were significantly important to patient choice preferences, except follow-up requirements. For each 1% higher risk of death within 5 years, preference utility was lower by 2.22 ( β =-2.22; 95% confidence interval [CI], -2.52 to -1.91), while for each 1% higher risk of serious infection, utility was lower by 1.38 ( β =-1.46; 95% CI, -1.77 to -1.00) according to comparisons of the β coefficients. Patients were willing to trade a 1% infection risk and 0.5% risk of death to gain complete mobility and freedom from in-center hemodialysis ( β =1.46; 95% CI, 1.27 to 1.64). Despite an aversion to even a 1% higher risk of death within 5 years, serious infection, and permanent device rejection, patients with kidney failure suggested that they would trade these risks for the benefit of complete mobility.

Fluoroquinolone prophylaxis in patients with neutropenia at high risk of serious infections: Exploring pros and cons.

The use of fluoroquinolones to prevent infections in neutropenic patients with cancer or undergoing hematopoietic stem cell transplantation (HSCT) is a controversial issue, with international guidelines providing conflicting recommendations. Although potential benefits are clear, concerns revolve around efficacy, potential harms, and antimicrobial resistance (AMR) implications. Fluoroquinolone prophylaxis reduces neutropenic fever (NF) bloodstream infections and other serious bacterial infections, based on evidence from systematic reviews, randomized controlled trials, and observational studies in adults and children. Fluoroquinolone prophylaxis may also reduce infection-related morbidity and healthcare costs; however, evidence is conflicting. Adverse effects of fluoroquinolones are well recognized in the general population; however, studies in the cancer cohort where it is used for a defined period of neutropenia have not reflected this. The largest concern for routine use of fluoroquinolone prophylaxis remains AMR, as many, but not all, observational studies have found that fluoroquinolone prophylaxis might increase the risk of AMR, and some studies have suggested negative impacts on patient outcomes as a result. The debate surrounding fluoroquinolone prophylaxis calls for individualized risk assessment based on patient characteristics and local AMR patterns, and prophylaxis should be restricted to patients at the highest risk of serious infection during the highest risk periods to ensure that the risk-benefit analysis is in favor of individual and community benefit. More research is needed to address important unanswered questions about fluoroquinolone prophylaxis in neutropenic patients with cancer or receiving HSCT.

Sustained post-rituximab B-cell depletion is common in ANCA-associated vasculitis and is affected by sex and renal function.

Despite the increasing use of rituximab in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), it remains unclear what the optimal dosing is, especially for maintenance of remission. A deeper understanding of post-rituximab B-cell repopulation patterns may aid better-tailored treatment. This is a monocentric, retrospective study including ANCA-positive AAV patients receiving a single course of rituximab induction. CD19+ B cells were longitudinally monitored with flow cytometry. B-cell repopulation was defined as CD19+ >10 cells/μL. Seventy-one patients were included, the majority with microscopic polyangiitis (75%), myeloperoxidase-ANCA positivity (75%) and with renal involvement (79%). During a median follow-up of 54months since the first rituximab infusion, 44 patients (62%) repopulated B cells, with a median time to repopulation of 39months (range 7-102). Patients experiencing B-cell depletion lasting longer than the overall median time to repopulation (39months) exhibited a lower risk of flare and higher risk of serious infection. In multivariate Cox regression, higher estimated glomerular filtration rate (eGFR) [hazard ratio (HR) 1.84, 95% confidence interval (CI) 1.13-2.98 per 30mL/min/1.73 m2 eGFR] and female sex (HR 2.70, 95% CI 1.37-5.31) were independent predictors of increased rate of B-cell repopulation. A subset of AAV patients develop sustained post-rituximab B-cell depletion, which associates with reduced risk of flare and increased risk of serious infection in the long term. Preserved renal function and female sex are associated with faster B-cell repopulation. These observations further highlight the need to personalize immunosuppression to improve clinical outcomes.

Risk of serious infection and infection mortality in patients with psoriasis: A nationwide cohort study using the Taiwan National Health Insurance claims database.

The risks of serious infections that lead to hospitalization and mortality in patients with psoriasis in Asia have not been comprehensively studied. We examined the incidence of serious infection and infection mortality in patients with psoriasis. This population-based retrospective cohort study used the Taiwan National Health Insurance claims database from 2000 to 2017. Adult patients with psoriasis were identified by a relevant International Classification of Diseases (ICD) code and matched to six comparators without psoriasis on age and sex. Psoriasis patients were categorized as having moderate-to-severe disease once exposed to systemic therapies, phototherapy or biologic therapies. The incidence of serious infection and infection mortality were identified by ICD codes from inpatient hospitalization and death registration. Cox proportional hazard models were used to compare the risk, and the results were adjusted for covariates and presented as adjusted hazard ratios (aHR) and 95% confidence interval (95% CI). Overall, 185,434 psoriasis patients and 1,112,581 comparators were included. A higher rate of serious infection (aHR: 1.21, 95% CI: 1.19-1.22) was found in patients with psoriasis compared to matched comparators without psoriasis, and the risk was enhanced when patients had moderate-to-severe psoriasis (aHR: 1.30, 95% CI: 1.27-1.34). Specifically, there was an increased risk of serious infection due to respiratory infections (aHR: 1.11, 95% CI: 1.09-1.13), skin/soft-tissue infections (aHR: 1.57, 95% CI: 1.52-1.62), sepsis (aHR: 1.23, 95% CI: 1.19-1.27), urinary tract infections (aHR: 1.11, 95% CI: 1.08-1.14), hepatitis B (aHR: 1.18, 95% CI: 1.06-1.30) and hepatitis C (aHR: 1.49, 95% CI: 1.32-1.69). Furthermore, psoriasis patients were associated with a higher risk of infection-related mortality (aHR: 1.15, 95% CI: 1.11-1.18) compared to matched comparators. Patients with psoriasis had a higher risk of serious infection and infection mortality, which was enhanced by moderate-to-severe psoriasis. Practitioners should be aware of the increased risk in patients with psoriasis, but it should not be a barrier to offering effective treatment.

Comparative short-term risks of infection and serious infection in patients receiving biologic and small-molecule therapies for psoriasis and psoriatic arthritis: a systemic review and network meta-analysis of randomized controlled trials.

Infection events are a major concern for patients and physicians when making psoriasis treatment decisions. To estimate the relative short-term risks of infection and serious infection for biologic and small molecule therapies in the treatment of moderate-to-severe plaque psoriasis (PsO) and psoriatic arthritis (PsA). A systematic literature search of the PubMed, EMBASE, and Web of Science databases was conducted on 17 June 2022. We included phase II, III, or IV randomized controlled trials (RCTs) of biologic and small-molecule therapies that are licensed or likely to gain approval soon for PsO and PsA, as well as infection data reports. Two investigators independently extracted the data based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis (NMA) was performed to estimate the pooled relative risks (RRs) and corresponding 95% confidence intervals of total infections and serious infections for treatments during placebo-controlled phases of RCTs. The surface under the cumulative ranking area (SUCRA) was calculated to rank the infection risk for each treatment. A total of 94 RCTs with a total of 19 treatment arms involving 54,369 participants were analyzed. For patients with PsO, bimekizumab, secukizumab, risankizumab, ustekinumab, apremilast, guselkumab, and adalimumab were associated with significantly higher risks of infection than placebo; SUCRA ranked infliximab, deucravacitinib, and bimekizumab with the highest risks of infection. For patients with PsA, bimekizumab, apremilast, and upadacitinib (30 mg daily) were associated with higher risks of infection; SUCRA ranked bimekizumab with the highest risk of infection. No treatments, except for upadacitinib (30 mg daily), were associated with a higher risk of serious infection than placebo in PsA. This NMA provides a comprehensive assessment of the comparative short-term risks of infection, which could help physicians and patients to select individualized treatments for psoriasis. CRD42022359873.

Accuracy of Tissue Oxygen Saturation Measurements of a Textile-Based NIRS Sensor.

Pressure injuries (PI) are dangerous tissue lesions that heal very slowly and pose a high risk of serious infections. They are caused by pressure applied to the tissue, which stops blood circulation and therefore induces hypoxia, i.e., low tissue oxygen saturation (StO2). PI cause severe suffering and are expensive to treat. Hence it is essential to prevent them with a device that detects a dangerous situation, e.g., by measuring StO2 using near-infrared spectroscopy (NIRS). For such a device to be wearable without causing PI, it must not introduce pressure points itself. This can be achieved by integrating optical fibers into a textile to transport light to and from the tissue.The aim of this paper is to investigate the accuracy of StO2 measurements using a NIRS device based only on textile-integrated optical fibers.Bundles of fibers were stitched into a textile in such a way that loops of <1 mm diameters were formed at the stitching locations. Detection points (DPs) on the fabric consisted of 8 fibers with 3 loops each. Emission points (EPs) were made from 4 fibers with 3 loops each. All fiber ends of a DP were connected to an avalanche photodiode. One end of each fiber belonging to an EP was connected to an LED (740nm, 810nm, or 880nm; 290, 560, or 610mW).To verify the accuracy of this textile-based sensor, we placed it on a subject's forearm and compared the derived StO2 during arterial occlusion to the values of a gold-standard NIRS device (ISS Imagent), which was placed on the forearm too.We found that our textile-based sensor repeatedly measured StO2 values over a range of 40% with a deviation of <10% from the reference device.By showing the ability to measure StO2 using textile-integrated optical fibers accurately, we have reached a significant milestone on our way to building a wearable device to monitor tissue health and prevent PI.

Vaccine Schedule Disparities Exist for Pediatric Patients with Sickle Cell Disease

Background: Sickle cell centers and pediatricians often work together to ensure appropriate vaccination of patients with sickle cell disease (SCD). Patients with SCD are at high risk for serious infections with encapsulated bacteria, such as Neisseria menigitidis and Streptococcus pneumoniae; thus, vaccine recommendations for pediatric patients with SCD differ from those for the general population. The University of Alabama at Birmingham Lifespan Comprehensive Sickle Cell Center (UAB) encompasses four care locations: the academic center in Birmingham and three satellite clinics (Montgomery, Opelika, Tuscaloosa). Unlike the academic center where providers are reliant on pediatricians to ensure adherence to recommended vaccines (with the exception of PPSV23), patients seen in the satellite clinics are provided with a prescription for PPSV23 and instructed to obtain it through their pediatrician. Data from prior studies suggest that pediatric patients with SCD may have lower vaccination rates than the general population. Thus, the purpose of this study was to determine adherence to recommended SCD-specific vaccination schedules among pediatric patients cared for at UAB , by: 1) determining the mean age at initiation of the HPV, MenACWY, Men B, and PPSV23 vaccines among UAB pediatric patients, compared with SCD-specific recommendations for initiation of each of these vaccines; and 2) comparing vaccination rates for HPV, MenACWY, and Men B among UAB pediatric patients age 13-17 years vs. general population peers. Methods: We performed a retrospective chart review of clinic notes and the Alabama state vaccine registry (Immunization Patient Registry with Integrated Technology [ImmPRINT]) for records of UAB patients, to determine the age at vaccine initiation and number of doses received for HPV, MenACWY, Men B, and PPSV23 vaccines for all 870 UAB patients aged 3-22 years. We calculated the mean age at which the UAB patients initiated each vaccine, the proportion of patients completing each vaccine series, and (for PPSV23) whether patients were vaccinated at UAB or at another location. We used CDC published vaccination rates for HPV, MenACWY, and MenB from 13-17-year-olds in the general population (Pingali et al., MMWR Morb Wkly Rep 2021) to compare with rates from UAB patient peers. Results: The 870 UAB patients were an average age of 12.1 ± 5.4 years; 51.5% were male and 33.9% received most of their care at satellite clinics. HPV vaccination: Mean ±SD age at HPV vaccine initiation was 11.3±1.2 years (recommended age at first dose=11 years, there are no SCD-specific guidelines for HPV vaccination); coverage for HPV vaccine series initiation and completion among 13-17-year-old UAB patients vs. general population peers was 77.8% vs. 75.1% and 58.2% vs. 58.6%, respectively (Table). Meningococcal [MenACWY] vaccination: Mean±SD age at MenACWY initiation was 11.2±1.8 years (recommended age for patients with SCD is 2 months (MenACWY Menveo) or 24 months (MenACWY Menactra); recommended age for general population is 11 years). We found that patients with SCD were 32 (95% confidence interval [CI]: 22-47) times more likely to receive MenACWY after age 11 years. Meningococcal B [MenB] vaccination: Mean age at MenB initiation was 13.5±2.3 years (recommended age for SCD patients is 10 years; vaccine is optional for general population); coverage for ≥1 MenB dose among 13-17-year-old UAB patients vs. general population peers was 17.5% vs. 28.4%, respectively. PPSV23 vaccination: Overall PPSV23 coverage for UAB patients was 70.6%; patients seen at the academic medical center were 1.5 (95%CI, 1.1-2.0) times more likely to receive PPSV23 than patients seen at a satellite clinic (75.2% vs. 59.6%, respectively). Conclusion: Adherence to SCD-specific vaccination age recommendations is poor. We found that patients with SCD were more likely to receive vaccines according to the general population vaccine schedule rather than the SCD-specific vaccine schedule. In addition, reliance on pediatricians to provide PPSV23 for satellite clinic patients resulted in lower PPSV23 vaccination rates among these patients. These data suggest a disparity in adherence to SCD-specific vaccination schedules and suggest the need to develop and test a healthcare provider-focused intervention aimed at improving adherence to the SCD-specific vaccination schedule for children with SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

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

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

COVID-19 and diabetes-Two giants colliding: From pathophysiology to management.

Since December 2019, a new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread around the world, causing the coronavirus 2019 (COVID-19) pandemic. From the beginning, SARS-CoV-2 has put a strain on the health system. In fact, many patients have had severe forms of the disease with the need for hospitalization due to respiratory failure. To contain the pandemic, the most widely used approach has been lockdowns. Social restrictions have been reduced thanks to the development of vaccines and targeted therapies. However, fatal events still occur among people at high risk of serious infection, such as patients with concomitant diabetes. Different mechanisms have been proposed to explain the poor prognosis of patients with diabetes and COVID-19, but the specific cause is unclear. It is now known that insulin resistance, inflammation, and cytokine storm are involved. Moreover, SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptors to enter cells. This receptor is expressed on pancreatic beta cells and, during infection, it appears that receptor involvement may induce hyperglycemia in patients with or without diabetes. In this study, we discuss the mechanisms underlying the poor prognosis in people with COVID-19 and diabetes and what may improve the outcome in these patients.

Effectiveness and Safety of Biologic Therapy in Hispanic Vs Non-Hispanic Patients With Inflammatory Bowel Diseases: A CA-IBD Cohort Study

There are limited data on outcomes of biologic therapy in Hispanic patients with inflammatory bowel diseases (IBDs). We compared risk of hospitalization, surgery, and serious infections in Hispanic vs non-Hispanic patients with IBD in a multicenter, electronic health record-based cohort of biologic-treated patients. We identified adult patients with IBD who were new users of biologic agents (tumor necrosis factor α [TNF-α] antagonists, ustekinumab, vedolizumab) from 5 academic institutions in California between 2010 and 2017. We compared the risk of all-cause hospitalization, IBD-related surgery, and serious infections in Hispanic vs non-Hispanic patients using 1:4 propensity score matching and survival analysis. We compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% TNF-α antagonist-treated; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% TNF-α antagonist-treated; 27% with prior biologic exposure). After propensity score matching, Hispanic patients were younger (37 ± 15 vs 40 ± 16 y; P= .02) and had a higher burden of comorbidities (Elixhauser index, >0; 37% vs 26%; P < .01), without any differences in patterns of medication use, burden of inflammation, and hospitalizations. Within 1 year of biologic initiation, Hispanic patients had higher rates of hospitalizations (31% vs 23%; adjusted hazard ratio [aHR], 1.32; 95% CI, 1.01-1.74) and IBD-related surgery (7.1% vs 4.6%; aHR, 2.00; 95% CI, 1.07-3.72), with a trend toward higher risk of serious infections (8.8% vs 4.9%; aHR, 1.74; 95% CI, 0.99-3.05). In a multicenter, propensity score-matched cohort of biologic-treated patients with IBD, Hispanic patients experienced higher rates of hospitalization, surgery, and serious infections. Future studies are needed to investigate the biological, social, and environmental drivers of these differences.

Safety of sequential biological therapy in inflammatory bowel disease: results from a tertiary referral centre.

Biologicals represent the cornerstone of treatment for moderate-to-severe inflammatory bowel diseases (IBD). Many patients cycle between biologicals when encountering loss of response or adverse events. To assess the occurrence of serious infections and malignancies with exposure to several (classes of) biologicals. We performed a retrospective cohort study in a tertiary referral centre including consecutive IBD patients exposed to adalimumab, infliximab, ustekinumab or vedolizumab between 1996 and 2019. All serious infections and malignancies, as well as potential confounders, were accounted for. In total, 1575 patients were included with a median (interquartile range) follow-up of 10 (6-16) years and a duration of biological therapy of 71 (39-112) months. Incidence rates of serious infections were 3.4 per 100 patients' years (PY) in the post-biological setting. Serious infections after biological exposure were associated with systemic steroids in monotherapy (hazard ratio 2.96 [95% confidence interval 1.78-4.93], p< 0.0001), combination therapy of systemic steroids and a biological (2.44 [1.37-4.34], p= 0.002), female gender (1.25 [1.04-1.51], p= 0.02), and prior serious infections in the pre-biological setting (1.42 [1.03-1.96], p= 0.03). Malignancy rates were 1.06 per 100PY in the post-biological setting and increased with older age at biological initiation (1.04 [1.02-1.05], p< 0.0001). The risk for serious infections or malignancies was independent of type and number of biologicals to which the patient was exposed. This study shows that the sequential use of biological therapy in IBD does not seem to convey an overall higher risk of serious infections or malignancies, but that underlying more refractory disease seems to increase this risk.

High Rates of Serious Infections in Childhood IBD

High Rates of Serious Infections in Childhood IBD

Clinical Features of Infection in Newly Diagnosed Patients with Myelodysplastic Syndrome and Its Correlation with Curative Effect

To explore the characteristics of infection in patients with myelodysplastic syndromes (MDS), risk factors of serious infection, and their correlation with curative effect. The clinical data of 92 newly diagnosed MDS patients with nosocomial infection from January 2016 to June 2020 in our hospital were retrospectively analyzed. A total of 306 courses of treatment were completed in 92 newly diagnosed MDS patients. The infection rate was the highest in the first course of treatment (84.8%, 78/92), and then decreased gradually. The top three infection sites were lung, upper respiratory tract, and gastrointestinal tract. A total of 90 strains of pathogenic bacteria were detected, of which 33.4% (30/90) were gram-negative bacilli, 23.3% (21/90) were gram-positive cocci, 23.3% (21/90) were fungi, and 20.0% (18/90) were viruses. The serious infection rate among 92 patients with MDS was 22.8% (21/92). Multivariate analysis showed that neutrophil deficiency>7 days (OR=10.875, 95%CI: 2.747-43.051, P=0.001) was an independent risk factor for serious infection in MDS patients. Compared with non-severe infection group, the total effective rate of severe infection group was lower (90.9% vs 63.6%, χ2=4.393, P<0.05). The infection rate of MDS patients is high in the first course of treatment, and the most common infection site is the lung. Gram-negative bacteria is the most common pathogen. MDS patients with neutrophil deficiency>7 days have a high risk of serious infection and poor efficacy.

A retrospective cohort study of infection risk in hospitalized patients evaluated for Sweet syndrome.

Sweet syndrome (SS) is divided into malignancy-associated, classical, and drug-induced subtypes. Features associated with SS, such as fevers, neutropenia, and cancer, are also high risk for serious infection. We aimed to describe hospitalized patients with a documented concern for SS on initial dermatologic evaluation, their risk of infection, and the impact of SS subtype on treatment and outcomes. We descriptively analyzed hospitalizations at The Ohio State University evaluated for SS by dermatology and performed a retrospective cohort analysis of malignancy-associated and non-malignancy-associated SS patients. Eighty-seven patient hospitalizations were evaluated for SS from 2012 to 2019. Thirty-one hospitalizations were complicated by neutropenia. Lesions in 12.9% (n = 4/31) of neutropenic hospitalizations were infected with Fusarium species (n = 2) or methicillin-resistant staphylococcus aureus (n = 2). One patient with fungal disease died within 30days of hospitalization. Thirty-three patients were confirmed to have a final diagnosis of SS. In the confirmed SS cohort, malignancy was associated with greater overall dapsone use (p = .021), less initial (p = .046) and overall (p = .013) corticosteroid use, and fewer SS-related readmissions within one year (p = .020) and overall (p = .004). Corticosteroid treatment delay should be considered for a short period in neutropenic patients while excluding infection. Malignancy-associated SS patients were more frequently treated with dapsone and favorable outcomes were seen in cancer patients.

Design and development of advanced glucose biosensors via tuned interactions between marine polysaccharides and diagnostic elements – A survey

Extensive scientific analysis on the susceptibility of different populations to COVID-19 highlights that compared to populations with no co-morbidities, people with co-morbidities such as diabetes mellitus (DM) are at a significantly higher risk of serious infection, hospitalization, or even death. This underscores the importance of controlling DM through self-monitoring of blood glucose (SMBG) or continuous glucose monitoring (CGM) using biosensors. These biosensors, which can be either enzymatic or non-enzymatic, have undergone several rounds of development in terms of the materials used for device construction. In terms of the immobilization agent needed to anchor enzymatic or non-enzymatic detection elements to the electrode surface, marine polysaccharides, such as chitosan and alginate, hold a distinct advantage. This, in turn, can be ascribed to their biocompatibility, chemical stability, film-forming ability, functionality bind with enzymes/diagnostic elements, and easy availability. In this review, we focus extensively on the use of cationic chitosan and anionic alginate in the past decade for designing advanced glucose biosensors. Their role in enhancing sensor response via physical/chemical interactions with the conducting and diagnostic elements is analyzed in detail from a structural point of view. In addition, the possibility of using these polysaccharides in non-invasive CGM sensors is discussed and several potential future research avenues are presented.