Infectious Complications In Patients Research Articles

Association of using enteral nutrition containing probiotics and dietary inflammatory index with inflammatory factors serum levels and gastrointestinal complications in infected patients with COVID-19

Purpose This paper aims to examine the association between the dietary inflammatory index, the consumption of Enteral Nutrition Supplemented with probiotics with certain serum inflammation markers and gastrointestinal complications among individuals diagnosed with COVID-19. Design/methodology/approach This cross-sectional investigation involved 100 COVID-19 patients who were admitted to intensive care units in hospitals. These patients were administered two different types of Enteral Nutrition, so the dietary inflammatory index (DII), gastrointestinal complications and some serum inflammation markers have been compared between two groups. Findings The mean DII scores in all patients were significantly pro-inflammatory (probiotic formula 2.81 ± 0.01 vs usual formula group 2.93 ± 0.14 p = 0.19). The probiotic formula consumption had an inverse association with High-sensitivity C-reactive Protein concentration (coef = −3.19, 95% CI −1.25, −5.14 p = 0.001) and lead to a reduction of 2.14 mm/h in the serum level of Erythrocyte sedimentation rate compared to normal formula. The incidence of diarrhea, abdominal pain and vomiting in probiotic formula patients was respectively 94%, 14% and 86% less than in usual formula patients (p = 0.05). Originality/value In this cross-sectional study for the first time, the authors found that probiotic formula consumption was inversely associated with serum inflammation markers and gastrointestinal complications incidence. The high DII leads to more gastrointestinal complications incidence and inflammation markers. More studies are needed to prove this relationship.

The association between renal pelvis urine density and the risk of severe infectious complications in patient with symptom-free hydronephrosis after shock wave lithotripsy: a multi-center prospective study.

Finding reliable and easy-to-obtain predictors of severe infectious complications after shock wave lithotripsy (SWL) is a major clinical need, particular in symptom-free hydronephrosis. Therefore, we aim to prospectively investigate the predictive value of Hounsfield units (HU) in renal pelvis urine for the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL. This multi-center prospective study was conducted from June 2020 to December 2023. The HU of renal pelvis urine was measured by non-enhanced computed tomography. The severe infectious complications included systemic inflammatory response syndrome, sepsis, and septic shock. Binary logistic regression models assessed the odds ratios (ORs) and 95% confidence intervals (CIs). Finally, 1,436 patients with ureteral stones were enrolled in this study. 8.9% (128/1,436) of patients experienced severe infectious complications after SWL treatment. After adjusting confounding variables, compared with the patients in the lowest renal pelvis urine density quartile, the OR (95% CI) for the highest quartile was 32.36 (13.32, 78.60). There was a positive linear association between the HU value of renal pelvis urine and the risk of severe infectious complications after SWL (P for trend < 0.001). Furthermore, this association was also observed stratified by age, gender, BMI, stone size, stone location and hydronephrosis grade (all P for interaction > 0.05). Additionally, the nonlinear association employed by restricted cubic splines is not statistically significant (nonlinear P = 0.256). The AUROC and 95%CI of renal pelvis urine density were 0.895 (0.862 to 0.927, P value < 0.001). The cut-off value was 12.0 HU with 78.59% sensitivity and 85.94% specificity. This multi-center prospective study demonstrated a positive linear association between HU in renal pelvis urine and the risk of severe infectious complications in patients with ureteral stones and symptom-free hydronephrosis after SWL, regardless of age, gender, BMI, stone size, stone location, and hydronephrosis grade. These findings might be helpful in the SWL treatment decision-making process.

Ten Tips on Immunosuppression in Primary Membranous Nephropathy

Abstract Membranous nephropathy (MN) management poses challenges, particularly in selecting appropriate immunosuppressive treatments (IST) and monitoring disease progression and complications. This manuscript highlights ten key tips for the management of primary MN based on current evidence and clinical experience. First, we advise against prescribing immunosuppressive treatment (IST) to patients without nephrotic syndrome, emphasizing the need for close monitoring of disease progression. Second, we recommend initiating IST in patients with persistent nephrotic syndrome or declining kidney function. Third, we suggest prescribing rituximab or rituximab combined with calcineurin inhibitors (CNI) in medium-risk patients. Fourth, we propose cyclophosphamide-based immunosuppression for high-risk patients. Fifth, we discourage the use of glucocorticoid monotherapy or mycophenolate mofetil as initial treatments. Sixth, we underscore the importance of preventing infectious complications in patients receiving IST. Seventh, we emphasize the need for personalized monitoring of IST by closely measuring kidney function, proteinuria, serum albumin, and anti-PLA2R levels. Eighth, we recommend a stepwise approach in the treatment of resistant disease. Ninth, we advise adjusting treatment for relapses based on individual risk profiles. Finally, we caution about the potential recurrence of MN after kidney transplantation and suggests appropriate monitoring and treatment strategies for post-transplantation MN. These tips provide comprehensive guidance for clinicians managing MN, aiming to optimize patient outcomes and minimize complications.

Frequency of infections during rituximab treatment of autoimmune blistering diseases.

This study investigates the frequency of infections in autoimmune blistering disease (AIBD) patients treated with rituximab and evaluates the difference in infectious complications in patients on concomitant antibiotic and/or antiviral prophylaxis. The study retrospectively reviewed 43 AIBD patients who received rituximab over a five-year interval. The patients were categorized based on prophylaxis type (antibiotic, antiviral, or both) and concomitant immunosuppression status, which we defined as treatment with an immunosuppressive medication during the time frame they were given Rituximab. Our findings suggest that concomitant immunosuppression alongside rituximab did not significantly increase the risk of developing infectious complications compared to rituximab monotherapy. Results revealed that 34.4% of patients with concomitant immunosuppression had a secondary bacterial infection, defined as bacterial complications requiring hospitalization, consistent with prior studies. Moreover, antibiotic prophylaxis did not significantly reduce infection risk in patients on rituximab, with 45.1% of these patients experiencing bacterial complications. There was an absence of pneumocystis pneumonia in the study population. Despite the small sample size and limited timeline, this study suggests that antibiotic prophylaxis may not significantly mitigate the risk of infections in AIBD patients receiving rituximab, and the risk of infection with concomitant immunosuppression with rituximab requires additional investigation for definitive causal risk.

Infectious complications in pediatric patients after liver transplantation in the first 3 months at the Fundación Valle del Lili, a Latin American transplant center

IntroductionIn pediatric patients undergoing liver transplantation, infections are one of the primary complications. The etiology varies depending on the time elapsed post-transplant, with early presentations of bacterial and fungal infections, followed by viral and parasitic infections. There is limited literature describing the prevalence of infectious complications in this group of patients in Colombia. ObjectiveTo describe infectious complications in patients undergoing liver transplantation within the first 3 months post-procedure at the Fundación Valle del Lili, Cali, Colombia. MethodsA case series of 165 pediatric liver transplant patients during the period 2011–2017. A descriptive analysis of all entered data was conducted. Survival analysis using the Kaplan-Meier method was performed, with an exploratory analysis comparing patient survival based on the presence of infection, censored for death related to postoperative complications. ResultsThe primary diagnosis at the time of transplantation was biliary atresia in 65% of cases. A total of 215 infectious episodes were recorded in 92 pediatric liver transplants. The most frequent microorganisms were Klebsiella pneumoniae (21%), Cytomegalovirus (CMV) (7%), Pseudomonas aeruginosa (7%), Escherichia coli (6%), and Epstein Barr Virus (EBV) (6%). Three-month patient survival was 92% for infection-related mortality. DiscussionInfectious complications within the first three months post-pediatric liver transplantation were predominantly bacterial in origin. Bacterial and fungal infections manifested earlier, while viral infections appeared later. Infectious complications did not impact the three-month patient survival in this group.

Exploring the Antiviral Potential of Esters of Cinnamic Acids with Quercetin.

Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) has infected more than 762 million people to date and has caused approximately 7 million deaths all around the world, involving more than 187 countries. Although currently available vaccines show high efficacy in preventing severe respiratory complications in infected patients, the high number of mutations in the S proteins of the current variants is responsible for the high level of immune evasion and transmissibility of the virus and the reduced effectiveness of acquired immunity. In this scenario, the development of safe and effective drugs of synthetic or natural origin to suppress viral replication and treat acute forms of COVID-19 remains a valid therapeutic challenge. Given the successful history of flavonoids-based drug discovery, we developed esters of substituted cinnamic acids with quercetin to evaluate their in vitro activity against a broad spectrum of Coronaviruses. Interestingly, two derivatives, the 3,4-methylenedioxy 6 and the ester of acid 7, have proved to be effective in reducing OC43-induced cytopathogenicity, showing interesting EC50s profiles. The ester of synaptic acid 7 in particular, which is not endowed with relevant cytotoxicity under any of the tested conditions, turned out to be active against OC43 and SARS-CoV-2, showing a promising EC50. Therefore, said compound was selected as the lead object of further analysis. When tested in a yield reduction, assay 7 produced a significant dose-dependent reduction in viral titer. However, the compound was not virucidal, as exposure to high concentrations of it did not affect viral infectivity, nor did it affect hCoV-OC43 penetration into pre-treated host cells. Additional studies on the action mechanism have suggested that our derivative may inhibit viral endocytosis by reducing viral attachment to host cells.

The impact of COVID-19 on cardiovasuar system

Background. Recent scientific reports have shown that there is a correlation between Covid 19 infection and cardiovascular function. This virus can exacerbate existing cardiovascular diseases and also cause the onset of new cardiovascular diseases. The purpose of this review is to present the effects of SARS-COV-2 virus infection on the cardiovascular system. Review methods. The literature review was conducted using the PubMed search engine. Brief description of the state of knowledge. Individuals with cardiovascular disease who have contracted the virus are at higher risk for serious clinical complications such as myocarditis, heart failure and pulmonary embolism, leading to higher mortality rates in this group of patients. The pathophysiological mechanisms underlying the effects of COVID-19 on the cardiovascular system are still poorly understood. However, the results of this review suggest that it may cause direct myocardial damage, as well as contribute to the development of cytokine storm effect and right ventricular burden due to pulmonary embolism. Conclusions. COVID 19 pandemic and cardiovascular disease are currently a great challenge for modern medicine. The fact that the two disease entities interact makes it crucial to further explore the relationship between these diseases. This review underscores the need for continued research into the effects of COVID-19 on the cardiovascular system, as well as the importance of early detection and treatment of cardiovascular complications in infected patients.

The impact of COVID-19 on cardiovasuar system

Background. Recent scientific reports have shown that there is a correlation between Covid 19 infection and cardiovascular function. This virus can exacerbate existing cardiovascular diseases and also cause the onset of new cardiovascular diseases. The purpose of this review is to present the effects of SARS-COV-2 virus infection on the cardiovascular system. Review methods. The literature review was conducted using the PubMed search engine. Brief description of the state of knowledge. Individuals with cardiovascular disease who have contracted the virus are at higher risk for serious clinical complications such as myocarditis, heart failure and pulmonary embolism, leading to higher mortality rates in this group of patients. The pathophysiological mechanisms underlying the effects of COVID-19 on the cardiovascular system are still poorly understood. However, the results of this review suggest that it may cause direct myocardial damage, as well as contribute to the development of cytokine storm effect and right ventricular burden due to pulmonary embolism. Conclusions. COVID 19 pandemic and cardiovascular disease are currently a great challenge for modern medicine. The fact that the two disease entities interact makes it crucial to further explore the relationship between these diseases. This review underscores the need for continued research into the effects of COVID-19 on the cardiovascular system, as well as the importance of early detection and treatment of cardiovascular complications in infected patients.

Endoscopic stone surgery in patients having asymptomatic bacteriuria

Introduction. Endoscopic surgery for the treatment of urolithiasis is highly effective but is associated with the risk of infectious complications. Nevertheless, endoscopy is also associated with the risk of postoperative infectious complications, the primary risk factor being positive urine culture. Considering the possibility of detecting persistent asymptomatic bacteriuria (ASB) in this patients amid the shortfall of clear algorithms and schemes of ASB management before endoscopy, a comparative analysis of infectious complications in patients with sterile urine and persistent ASB undergoing endoscopic surgery for renal and ureteral stones is an urgent task.Оbjective. Analysis of the risk of infectious complications in patients undergoing endoscopic treatment of urinary stones, including those with preoperative evidence of asymptomatic bacteriuria.Materials &amp; methods. We conducted a cohort, retrospective study of data from eligible patients who underwent endoscopic removal of renal and ureteral stones between January 2023 and July 2023. From the 449 patient records selected, 211 patients fulfilling the established inclusion and non-inclusion criteria were enrolled in further analyses. Antibacterial prophylaxis was administered a few hours before surgery for initial sterile urine culture, three days before surgery for clinically insignificant ASB, and seven days before surgery for clinically significant ASB, followed by repeat control urine culture and determination of antibacterial prophylaxis according to the proposed methodology.Results. A preoperative sterile urine culture was diagnosed in 152 patients (72.0%), while 59 patients 28% [22%; 34.5%] were found to have bacteriuria, of which 28 patients 13.3% [9%; 18.6%] had clinically significant bacteriuria at a titer of ≥ 105 CFU/mL. After antibiotic therapy, ASB persisted in six patients (22.0%). Accordingly, 37 patients 17.5% [12.79%; 23.4%] with clinically significant and insignificant ASB underwent endoscopic surgery. In the postoperative period, 54 patients (25.6%) had leukocytosis, 17 patients (8.1%) had hyperthermia, and 11 patients (5.2%) had fever accompanied by leukocytosis One patient (0.5%) had an elevated procalcitonin level, which may indicate a systemic inflammatory response. Logistic regression analysis revealed statistically significant associations between the probability of hyperthermia and bacteriuria. A positive urine culture increased the odds of hyperthermia 4.75-fold (OR = 4,75, 95% CI [1.222; 18.803], p = 0.023). Maximum stone size (p = 0.013), stone volume, and ureteral stent drainage (p = 0.006) were the factors influencing the development of leukocytosis. Moreover, the volume of the stone increases the odds of leukocytosis by 1.54 times (OR = 1.543, 95% CI [1.128; 2.158], p = 0.008) for a 1.0 cc enlargement.Conclusion. Our study shows that a positive urine culture is a significant risk factor for infectious complications after endoscopic surgery. Prolonged courses of antibiotic prophylaxis lasting seven and three days in patients having clinically significant and clinically insignificant ASB, respectively, seem adequate to minimize the risk of postoperative infectious complications.

Risk of Infection in Patients With Inflammatory Bowel Disease Treated With Interleukin-Targeting Agents: A Systematic Review and Meta-Analysis.

Patients with inflammatory bowel disease (IBD) are at increased risk of infection. The aim of this study was to assess the cumulative incidence and risk of infection in patients with IBD treated with interleukin (IL)-targeting agents. We searched PubMed, EMBASE, and Web of Science for randomized controlled trials including patients with IBD receiving IL-targeting agents compared with patients receiving placebo or treatment that only differed from the intervention arm in the absence of an IL-targeting agent. The primary outcome of interest was the relative risk (RR) of any-grade and severe infection during the induction phase. There was no difference in risk of any-grade (RR, 0.98; 95% confidence interval [CI], 0.89-1.09) or severe (RR, 0.64; 95% CI, 0.38-1.10) infection in patients receiving any IL-targeting agent compared with the control group. During the maintenance period, the cumulative incidence of any-grade infection in patients receiving IL-12/23p40-targeting agents (mean follow-up 29 weeks) was 34.82% (95% CI, 26.78%-43.32%), while the cumulative incidence of severe infection was 3.07% (95% CI, 0.93%-6.21%). The cumulative incidence of any-grade infection in patients receiving IL-23p19-targeting agents (mean follow-up 40.9 weeks) was 32.16% (95% CI, 20.63%-44.88%), while the cumulative incidence of severe infection was 1.75% (95% CI, 0.60%-3.36%). During the maintenance phase of the included studies, the incidence of infection was 30.66% (95% CI, 22.12%-39.90%) for any-grade and 1.59% (95% CI, 0.76%-2.63%) for severe infection in patients in the control group. There was no difference in risk of infection between patients with IBD who received IL-targeting agents compared with the control group. Case registries and randomized controlled trials reporting the safety of IL inhibitors should provide detailed information about the risk of specific infectious complications in patients with IBD receiving IL-targeting agents.

Comparison of Infectious Complications in Patients Receiving High-Dose Cyclophosphamide as GvHD Prophylaxis After Transplantation From A 9/10 HLA-Matched Unrelated Donor with Standard GvHD Prophylaxis After Transplant From A Fully Matched Related Donor.

The aim of this study was to evaluate whether cyclophosphamide administered after allogeneic stem cell transplantation (ASCT) from 9/10 HLA-Matched Unrelated Donors (MMUD) increases the rates of bacterial, fungal, viral infections, complications (hemorrhagic cystitis (HC)), and infection-related mortality compared to allogeneic stem cell transplantation from matched related donors (MRD). This is a retrospective multicenter study. 45 MMUD ASCT patients who received posttransplant cyclophosphamide+methotrexate+calcineurin inhibitor compared with 45 MRD ASCT patients who received methotrexate+calcineurin inhibitor. Although there was a statistically significant prolongation of neutrophil engraftment time in the PTCy arm, there was no statistically significant difference in bacterial infection frequencies between the groups (PTCy; 9 (20%), control; 8 (17.8%), p=0.778). The distribution of CMV infection in the first 100 days was similar (p=0.827), but the distribution of CMV infection rate between the 100th and 365th days was observed more frequently in the control group (p=0.005). HC rates and their grades were similar in both groups (PTCy; 4 (8.8%), control; 6 (13.3%) p=0.502). The rates of VZV infection and invasive aspergillosis were similar in the PTCy and control groups (13.3% in the PTCy and 17.8% in the control group p=0.561). There is also no statistically significant difference in survival analysis (OS, LFS, GRFS, RI, IRM, NRM) between groups. However, the incidence of cGVHD was significantly higher in the control group (P=0.035). The addition of PTCy to standard GvHD prophylaxis in MMUD ASCT does not lead to an increase in CMV reactivation, bacterial infections, invasive fungal infection, viral hemorrhagic cystitis, or mortality.

Challenges with medical tourism.

With the return of international travels to almost prepandemic levels, the number of patients who travel abroad to seek healthcare services is once again growing rapidly. Nevertheless, the expected benefits of medical tourism may be challenged by serious infectious complications. This review summarizes the evolving published evidence on infectious complications related with medical tourism of the last eighteen months. There has been an increase of reported infectious complications in patients who had received healthcare abroad. Such complications were frequently associated with serious and prolonged morbidity, repeated treatments and hospitalizations, high healthcare costs, and occasionally fatalities. A devastating outbreak of fungal meningitis occurred among US residents who underwent epidural anesthesia for cosmetic surgery in two clinics in Mexico. Overall, as of July 5, 2023 there were 31 cases with severe cerebrovascular complications and eight deaths. Infections caused by nontuberculum mycobacteria and Candida sp have been also reported the last years. Considering the expected expansion of medical tourism in the forthcoming years, public health authorities and scientific societies should raise awareness of such infections among physicians and other healthcare professionals and issue recommendations for their management. A system to report complications in patients receiving healthcare abroad is needed.

Infectious Complications in Patients with Myelodysplastic Syndromes: A Report from the Düsseldorf MDS Registry.

Despite notable advancements in infection prevention and treatment, individuals with hematologic malignancies still face the persistent threat of frequent and life-threatening complications. Those undergoing chemotherapy or other disease-modifying therapies are particularly vulnerable to developing infectious complications, increasing the risk of mortality. Myelodysplastic syndromes (MDS) predominantly affect the elderly, with the incidence rising with age and peaking at around 70 years. Patients with MDS commonly present with unexplained low blood-cell counts, primarily anemia, and often experience varying degrees of neutropenia as the disease progresses. In our subsequent retrospective study involving 1593 patients from the Düsseldorf MDS Registry, we aimed at outlining the incidence of infections in MDS patients and identifying factors contributing to heightened susceptibility to infectious complications in this population.

Association between fibrosis around the tumor and postoperative infectious complication in patients with esophageal cancer who underwent preoperative therapy.

Multidisciplinary treatment combining chemotherapy, chemo radiation therapy (CRT), and surgery has been utilized for advanced esophageal cancer. However, preoperative treatment could cause postoperative inflammation and complications. We hypothesized that fibrosis surrounding tumor tissue caused by preoperative treatment could inducepostoperative systemic inflammation and influence postoperative complications. Surgical specimens from patients with thoracic esophageal cancer who underwent preoperative CRT (38 cases) or chemotherapy (77 cases) and those who received no preoperative treatment (49 cases) were evaluated to measure the fibrotic area adjacent to the tumor (10mm from the tumor edge) by applying Azan staining. Pleural effusion and peripheral blood serum interleukin-6 levels were analyzed to evaluate local and systemic postoperative inflammation in 37 patients. The fibrotic areas around the tumors were significantly larger in patients who underwent preoperative CRT than in patients who underwent chemotherapy (p<0.001) or who had received no preoperative therapy (p<0.001). Infectious complications were higher in patients who underwent preoperative CRT than chemotherapy (p=0.047) or surgery alone (p<0.001). The patients with larger fibrotic areas had more infectious complications (p=0.028). Multivariate analysis showed that both a large fibrotic area and preoperative CRT were correlated with infectious complications, but not significantly. Pleural effusion interleukin-6 was significantly higher in patients who underwent preoperative CRT than in patients who received no preoperative therapy (p=0.013). A large fibrotic peritumoral esophageal tissue area after preoperative treatment could cause postoperative inflammatory response and infectious complications.

Infectious Complications in Patients with Hematologic Malignancies Receiving CD19 Vs. BCMA Targeted CAR-T Therapy

Infectious Complications in Patients with Hematologic Malignancies Receiving CD19 Vs. BCMA Targeted CAR-T Therapy

Agranulocytosis and secondary infection related to JAK inhibitors and IL-6 receptor blockers: a disproportionality analysis using the US Food and drug administration adverse event reporting system.

Background: Given that the fight against coronavirus disease 2019 (COVID-19) is not over, we aimed to explore the occurrence of agranulocytosis and infectious complications in patients with and without COVID-19 following immunoregulatory therapy based on real-world data. Methods: This was a retrospective disproportionality analysis based on the US Food and Drug Administration Adverse Event Reporting System (FAERS). All cases reported between the first quarter of 2004 and the fourth quarter of 2022 about Janus kinase inhibitors (baricitinib, tofacitinib, ruxolitinib) and interleukin-6 receptor blockers (tocilizumab, sarilumab) were collected. Disproportionality analyses were conducted by reporting odds ratio (ROR) and information component (IC). Results: A total of 211,363 cases were recognized from the FDA Adverse Event Reporting System database. Data analysis showed that tocilizumab (reporting odds ratio: 3.18, 95% CI: 3.18-3.29; information component: 1.37, 95% CI: 1.31-1.42), sarilumab (ROR: 1.64, 95% CI: 1.55-1.73; IC: 0.61, 95% CI: 0.43-0.79), baricitinib (ROR: 3.42, 95% CI: 3.19-3.67; IC: 1.43, 95% CI: 1.21-1.65), tofacitinib (ROR: 2.53, 95% CI: 2.49-2.57; IC: 1.11, 95% CI: 1.05-1.16), and ruxolitinib (ROR: 1.87, 95% CI: 1.83-1.91; IC: 0.77, 95% CI: 0.70-0.84) were all associated with secondary infection. The association in the combination group was higher than that in the monotherapy group (ROR: 4.69, 95% CI: 4.53-4.86; IC: 1.73, 95% CI: 1.62-1.84). As for agranulocytosis, tocilizumab (ROR: 1.61, 95% CI: 1.53-1.69; IC: 0.67, 95% CI: 0.50-0.84) and ruxolitinib (ROR: 2.32, 95% CI: 2.21-2.43; IC: 1.18, 95% CI: 1.02-1.33) showed the significant signals. The association was higher in the combination group than in the monotherapy group (ROR: 2.36, 95% CI: 2.15-2.58; IC: 1.20, 95% CI: 0.90-1.51). Secondary infection after treatment with tofacitinib (ROR: 1.37, 95% CI: 1.02-1.84), tocilizumab (ROR: 1.46, 95% CI: 1.01-2.09), and sarilumab (ROR: 2.46, 95% CI: 1.10-5.50) was reported more frequently in COVID-19 than in non-COVID-19 patients. Conclusion: Both Janus kinase inhibitors and interleukin-6 receptor blockers are significantly associated with secondary infection and agranulocytosis, and the combined treatment further increases the association. The correlation with secondary infection in patients treated with tofacitinib, tocilizumab, and sarilumab is higher in COVID-19 than in non-COVID-19 patients.

Circulating myeloid populations have prognostic utility in alcohol-related liver disease.

Alcohol-related liver disease (ARLD) accounts for over one third of all deaths from liver conditions, and mortality from alcohol-related liver disease has increased nearly five-fold over the last 30 years. Severe alcohol-related hepatitis almost always occurs in patients with a background of chronic liver disease with extensive fibrosis or cirrhosis, can precipitate 'acute on chronic' liver failure and has a high short-term mortality. Patients with alcohol-related liverdisease have impaired immune responses, and increased susceptibility to infections, thus prompt diagnosis of infection and careful patient management is required. The identification of early and non-invasive diagnostic and prognostic biomarkers in ARLD remains an unresolved challenge. Easily calculated predictors of infection and mortality are required for use in patients who often exhibit variable symptoms and disease severity and may not always present in a specialized gastroenterology unit. We have used a simple haematological analyser to rapidly measure circulating myeloid cell parameters across the ARLD spectrum. We demonstrate for the first time that immature granulocyte (IG) counts correlate with markers of disease severity, and our data suggests that elevated counts are associated with increased short-term mortality and risk of infection. Other myeloid populations such as eosinophils and basophils also show promise. Thus IG count has the potential to serve alongside established markers such as neutrophil: lymphocyte ratio as a simply calculated predictor of mortality and risk of infectious complications in patients with alcohol-related hepatitis. This would allow identification of patients who may require more intensive management.

Novel Hematological Parameters in the Assessment of the Extent of Cardiac Implantable Electronic Device-Related Infections

Background: Patients with infectious complications related to the presence of cardiac implantable electronic devices (CIED) constitute a heterogeneous group, ranging from local pocket infection (PI) to lead-related infectious endocarditis (LRIE) infection spreading along the leads to the endocardium. The detection of isolated LRIE and the assessment of the spread of infection in a patient with PI is often difficult and requires complex imaging and microbiological tests. The aim of the current study is to evaluate the usefulness of new simple hematological parameters in detecting infectious complications in patients with CIED, differentiating vegetation and vegetation-like masses, and assessing the extent of infections in patients with PI. Methods: A retrospective analysis of clinical data of 2909 patients (36.37% with CIED-related infections), undergoing transvenous lead extraction (TLE) procedures in three high-volume centres in the years 2006–2020, was conducted. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-platelet ratio (NPR), and lymphocyte-to-platelet ratio (LPR) in the diagnosis of CIED infections, evaluate the spread of the infectious process in patients with PI and differentiate additional structures related to the presence of lead. Results: The values of NLR and NPR were significantly higher in infectious patients than non-infectious controls (3.07 vs. 2.59; p &lt; 0.001, and 0.02 vs. 0.01; p = 0.008) and the area under the ROC curve (AUC) was 0.59; p &lt; 0.001 and 0.56; p &lt; 0.001, respectively. The high specificity of the new markers in detecting the infectious process was demonstrated: 72.82% for NLR (optimal cut-off value: 3.06) and 79.47% for NPR (optimal cut off value: 0.02). The values of NLR and NPR were significantly higher in patients with vegetations than in non-infectious patients with the presence of additional lead-related masses (3.37 vs. 2.61; p &lt; 0.001 and 0.03 vs. 0.02; p = 0.008). The AUC of NLR and NPR for the prediction of vegetations was 0.65; p &lt; 0.001 and 0.60; p &lt; 0.001 with the highest specificity of NPR (82.78%) and an optimal cut-off value of 0.03. NLR and NPR were higher in patients with LRIE compared to isolated PI (4.11 vs. 2.56; p &lt; 0.001 and 0.03 vs. 0.02; p &lt; 0.001) and the ROC curve analysis for coexistence LRIE with PI showed the AUC for NLR: 0.57; p &lt; 0.001 and AUC for NPR: 0.55; p = 0.001. High specificity in the detection of coexistence between PI and LRIE was demonstrated for NLR (87.33%), with an optimal cut-off value of 3.13. Conclusions: Novel hematological markers (NLR and NPR) are characterized by high specificity in the initial diagnosis of CIED infections, with optimal cut-off values of 3.06 and 0.02. NLR is also useful in the assessment of the spread of infection in patients with PI, with a calculated optimal cut-off value of 3.13. NPR may be helpful in the differentiation of vegetation and vegetation-like masses with an optimal cut-off value of 0.03.

Chronic Obstructive Pulmonary Disease and Previous Infections Have Impact on Infectious Complications in Patients with Chronic Lymphocytic Leukemia Treated with Venetoclax: A Multicentre Seifem Study

Introduction. Infections are a major source of morbidity and mortality in patients with Chronic Lymphocytic Leukemia (CLL). The development of targeted agents decreased the rate of these complications in comparison to standard chemoimmunotherapy regimens. However, these patients often elderly, with other comorbidities, heavily treated, experienced serious infections. The aim of our study was to evaluate the incidence of clinically or microbiologically documented bacterial, fungal and viral infectious complications in CLL patients treated with venetoclax. Methods. The retrospective multicenter study included CLL patients treated since 2017 with venetoclax single agent until progression or toxicity or venetoclax plus anti-CD20 antibody (mainly rituximab as part of VR protocol for 24 months or obinutuzumab as part of VO protocol for 12 months). Results. A total of 287 patients with CLL received venetoclax during the study period from 16 different institutions: 151 patients (52.6%) as monotherapy and 136 (47.4%) associated to anti-CD20 antibody. Basal characteristics of the whole population and of the two groups are summarized in Table 1. Patients of the first group were older, more frequently had del17/TP53mut, renal impairment and lower basal levels of IgG. They also showed more previous infections in the 12 months before the beginning of the treatment with venetoclax. We registered 284 infections of any grade. When comparing time of first infection between the patients treated with venetoclax and those treated with venetoclax plus anti-CD20 antibody, we registered a trend toward a higher rate of infection in the latter group after the first year (p=0.066). This difference was not confirmed when we focused on infections of grade 3-4 (p=0.521). One-hundred eighty-one infections of grade 1-2 developed in 114 patients (39.7%) during the study. Most of the infections involved the respiratory tract (106 events, 58.6%), followed by genitourinary tract (23, 12.7%) and gastrointestinal one (16, 8.8%). Pathogens implicated in the infections were isolated only in 57 (31.5%) cases: 36 viral, 18 bacterial and 3 fungal. We recorded 103 episodes of infections of grade 3-4, occurred in 73 patients (25.4%). The most common site of infection involved the respiratory tract (71 events, 68.9%), then we registered sepsis (13, 12.6%) and gastrointestinal tract infections (7 events, 6.8%). Of 103 severe infections, 64 (62.1%) were microbiologically proven, of whom 40 were viral, 21 bacterial and 3 fungal. When comparing patients with and without infection, COPD (p&amp;lt;0.001, OR 3.75), previous infections in the last 12 months (p&amp;lt;0.001, OR 3.15), renal impairment CrCl&amp;lt;70 (p = 0.049, OR 1.62), previous treatments (p=0.023; OR 1.196) and stage A (p=0.001; OR 0.2) were more frequently associated with infection in univariate analysis. In multivariate analysis COPD (p &amp;lt;0.001, OR 5.39) and previous infections (p=0.001, OR 2.57) resulted significant. Stratifying patients according to COPD and previous infections in the last 12 months we obtained 3 groups significantly different in terms of infective risk (p &amp;lt;0.001; figure 1). When considering only grade 3-4 infections, risk factors significant in the univariate analysis were COPD (p &amp;lt;0.001, OR 3.23), smoke (p=0.033, OR 1.98) and previous infections (p=0.020, OR 1.91). COPD was the unique significant variable in multivariate analysis (p=0.008, OR 2.62). Treatment was withdrawn for infections in 80 patients (27.9%): in 58 (20.2%) treatment was temporarily discontinued, while in 22 (7.7%) discontinuation was permanent. The infections that caused definitive withdrawals were mainly pneumonia (12 cases, 6 of whom from SarS-CoV2 infection) and sepsis (8 cases, 5 of whom after a SarS-CoV2 infection). A total of 83 patients (28.9%) died and the median OS was 55 months. The main causes of death were CLL progression in 36 cases and infection in 22 cases. Conclusions. This is a real-life study on 287 patients affected by LLC treated with venetoclax with the aim to describe the infectious complications in such population in routine clinical practice. The analysis found a significant rate of infections, most of grade 1-2: 39.7% of the patients experienced a grade 1-2 infection; 25.4% a grade 3-4 infection. The identification of additional infectious risk factors found a role of comorbidities such as COPD and previous infections; COPD resulted a risk factor also for infections of grade 3-4.

BCMA-Directed CAR-T Cell Therapy Is Associated with a Higher Risk of Infections: A Systematic Review and Meta-Analysis

Background: Chimeric antigen receptor (CAR) T-cell therapy is a rapidly evolving immunotherapy for hematological malignancies. With increasing access to this modality, there is an urgent need for a comprehensive understanding of infectious complications to optimize prophylaxis and improve clinical outcomes. We conducted a systematic review and meta-analysis to assess the incidence and characteristics of infectious complications in adult patients receiving CAR T-cell therapy. Methods: The study was registered on PROSPERO and we searched 5 electronic databases from inception to 2022. Each author independently screened titles, reviewed full texts to identify eligible studies and extracted data from included studies using Covidence, a data extraction tool for conduction of standard systematic reviews. A random effects model was used, and proportions were used as a measure of outcome. We assessed heterogeneity using I^2 statistic. Risk of bias assessments were conducted using the RoB 2.0 for RCTs and ROBINS I tool for non-RCTs. Results: Our search identified 12,441 studies of which 363 underwent full-text review (Figure 1). 33 studies were eligible for inclusion in the analysis and enrolled a total of 2866 patients. The pooled incidence of an infectious event in adult patients after CAR T-cell therapy was 38% (95%CI 0.31, 0.46; p&amp;lt;0.01; I2 = 98%]. No significant difference was noted in the incidence among studies with a longer follow up duration compared to studies with follow up of £ 30 days [40% (95% CI 0.30-0.50) vs 32% (95% CI 0.24-0.40), p=0.20 respectively]. BCMA-directed CAR T-cell therapies used for management of multiple myeloma had a significantly higher incidence of infectious complications compared to CD19 targeted agents, 64% (95% CI 0.53-0.74, I2 = 65%) versus 39% (95% CI 0.30-0.49; I2 = 98%; p &amp;lt;0.01) respectively, Figure 2. Clostridium difficile and Escherichia coli were the most common pathogens causing bacterial infections, while cytomegalovirus was the most commonly identified viral pathogen affecting these patients. Conclusion: In this study, BCMA-directed CAR T-cell therapies were associated with a significantly higher risk of infectious complications. The results of this study can guide the development of strategies to prevent and manage infectious complications in this patient population.