Level Of Immunosuppression Research Articles

The Role of Bronchoalveolar Lavage in Therapeutic Antimicrobial Choices for Hematologic Patients with Pulmonary Infiltrates

Background and Objectives: Lower respiratory tract infections are particularly frequent in hematological patients; their early diagnosis and the timely start of targeted therapy are essential. Bronchoalveolar lavage (BAL) can provide a microbiological sample from the lower airways in a minimally invasive way. This study aimed to determine the diagnostic yield of BAL in hematological patients for microbiological purposes and its influence on modifying the therapeutic strategy. Material and Methods: This multicenter, retrospective, observational study included data from 193 consecutive patients from two centers from January 2020 to October 2022. The patients underwent a bronchoscopy with BAL in cases of pulmonary infiltrates suspicious of pulmonary infection. The demographic data, presenting symptoms, level of immunosuppression, chest CT changes, BAL sampling results, and antimicrobiological drug administration were analyzed. Results: Of the 193 procedures, 143 (74.1%) were performed on hospitalized patients, while 50 were performed on outpatients. In 53.9% of the cases, the BAL isolated at least one germ; in particular, if the procedure was carried out within 72 h of presenting symptoms, the probability of isolating the germ increased significantly (74.3%, p = 0.04). Among the isolated germs, 59.4% were viruses, 28.6% were bacteria, and 12% were fungi. The patients with higher immunosuppression and the febrile ones underwent BAL earlier than the patients with mild immunosuppression (p = 0.01) and those with other presenting symptoms (p = 0.0001). BAL positivity led to a change in empirical antimicrobial therapy in 79 out of 104 cases (77% vs. 36.3%; p < 0.001); these data were also confirmed among the hospitalized patients (81% vs. 44%; p < 0.001). The isolation of a pathogen through BAL and the degree of patient immunosuppression negatively influenced patient survival (p < 0.05 and p < 0.01, respectively). Conclusions: BAL is confirmed as a valid approach for evaluating pulmonary infiltrates in hematological patients, given the excellent clinical impact and high diagnostic yield, mainly if performed early after symptom presentation. However, ongoing antimicrobial treatments at the time of BAL may have potentially affected the diagnostic yield of the procedure.

COVID-19 and HIV: Clinical Outcomes and Inflammatory Markers in a Cohort from a Reference Hospital in Rio de Janeiro, Brazil

Background: Severe COVID-19 presents a variety of clinical manifestations associated with inflammatory profiles. People living with HIV (PLWH) could face a higher risk of hospitalization and mortality from COVID-19, depending on their immunosuppression levels. This study describes inflammatory markers in COVID-19 clinical outcomes with and without HIV infection. Methods: We analyzed 112 inpatients of the Hospital Center for COVID-19 (INI/FIOCRUZ), including 22 cases of COVID-19 in PLWH (COVID/PLWH group). Plasma samples were tested for a panel of 15 cytokines by Luminex. Sociodemographic, clinical, and laboratory data were collected from patients’ clinical records. Results: COVID-19 individuals were stratified according to the WHO clinical severity profiles at hospitalization. Significant differences in clinical scores, symptoms (coughs), and the occurrence of HIV infection were found among the groups. Clinical blood parameters and plasma cytokines were analyzed among COVID-19 groups with distinct severity profiles. Critical COVID-19 cases showed higher levels of inflammatory markers (Bilirubin, D-dimer, PCR, and urea, as well as IL-8, IL-10, TNF-α, INF-α, IL-1β, IL-17A, IL-23, IL-6) than moderate and severe groups. The COVID/PLWH group had lower CD4 counts (64 cells/mm3) and cytokine levels than other COVID-19 patients. Conclusions: Overall, critically ill COVID-19 patients exhibited heightened inflammatory responses, while COVID/PLWH demonstrated unique immunological characteristics without increased mortality risk.

Serum BAFF levels are associated with the prognosis of idiopathic membranous nephropathy

Objective High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. Methods Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. Results Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6–72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405–0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202–0.648; p < 0.001). Conclusions A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.

Total Anti-oxidant Capacity and Immunosuppressive Drug Blood Levels after Kidney Transplantation: A Patent Perspective

Background: It is well known that acute or chronic kidney injury could be due to free radicals and pro-oxidants. This investigation aimed to monitor tacrolimus or cyclosporine blood trough levels and anti-oxidant capacity after kidney transplantation. Methods: There was no intervention in the routine management of transplant recipients. The sample size (n=70) included healthy individuals and kidney-transplanted recipients (n=25 on tacrolimus and n=10 on cyclosporine). The study population was matched for age. The attained information was examined by using the Statistical Package (SPSS Inc, Chicago, IL, USA). The significance level was considered as P ≤ 0.05. Results: In healthy individuals, the mean ± SD for the capacity of antioxidants was 91.9 ± 16.6 (u/ml), which was significantly higher when compared to the mean value of 28.5 ± 22.6 (u/ml) versus 24.7 ± 25.5 (u/ml), kidney recipients with tacrolimus versus cyclosporine (P ≤ 0.04) as immunosuppressive drugs. The mean value of tacrolimus levels was 14.6 ± 6.4 (ng/ml). The correlation between tacrolimus and cyclosporine trough levels and anti-oxidant capacity was 0.19 (P ≤ 0.14). There were no significant differences regarding age in cases and controls (P ≤ 42). Conclusion: This study showed that the capacity of anti-oxidants in kidney transplant recipients, those on tacrolimus or cyclosporine, might be lower than in healthy individuals. Subsequent investigations are recommended to delve into the therapeutic consequences of the influence of antioxidant therapies on the clinical outcomes of transplanted recipients. conclusion: Worldwide, our study is the first that showed that TAOC in kidney transplanted recipient was lower than controls

The Association Between Cytomegalovirus Infection and Kidney Damage in the Liver Transplant Setting.

The development of chronic kidney disease (CKD) is a common and significant complication, contributing to morbidity after liver transplantation (LT). Cytomegalovirus (CMV) infection is common in the overall population, and relevant reinfection after LT may occur. CMV-associated kidney damage has been discussed, but the clinical significance on CKD development after LT remains unclear. A total of 745 patients who underwent LT between 2006 and 2017 were included in this retrospective analysis. Clinical data, as well as laboratory parameters, were analyzed. Univariate and multivariate analysis were performed. The univariate analysis revealed significantly impaired estimated glomerular filtration rates (eGFRs) in patients with histories of CMV infection (81.4 (8-137) mL/min vs. 90.0 (5-147) mL/min; p = 0.004). This effect was confirmed in the multivariate analysis. Post-LT, eGFR was impaired in patients with CMV (re)infection at 6, 12, 36, and 60 months, 10 years, and 15 years after LT. Immunosuppressive levels were comparable between groups. Overall survival was negatively affected by CMV infection (p = 0.001). A clinically significant detrimental impact of CMV infection on renal function was observed, that could individualize clinical risk evaluation prior and after LT further. However, the pathophysiological mechanisms behind this observation are not yet understood.

Vaccination Against Androgen Receptor Splice Variants to Immunologically Target Prostate Cancer.

Background/Objectives: Androgen receptor (AR) expression and signaling are critical for the progression of prostate cancer and have been the therapeutic focus of prostate cancer for over 50 years. While a variety of agents have been developed to target this axis, many of these fail due to the emergent expression of AR RNA splice variants, such as AR-V7, that can signal independently of ligand binding. Other therapies, such as vaccination against prostate-specific antigens, have achieved FDA approvals but have fallen short of being incorporated as standard-of-care therapies for advanced prostate cancer. This may be due to the elevated level of immunosuppression observed in prostate cancer, which remains largely refractory to immune checkpoint blockade. Methods: We developed a vaccine targeting AR-V7, a common isoform associated with treatment resistance, and demonstrated its ability to elicit AR-V7-specific immunity and enable anti-tumor responses against AR-V7+ cancers in subcutaneous tumor models. Results: Our studies also revealed that AR-V7 expression conferred an immune suppressive phenotype that was significant in a non-AR-dependent prostate cancer model. Notably, in this model, we found that vaccination in combination with enzalutamide, an AR antagonist, suppressed these aggressive immune suppressive cancers and resulted in enhanced survival in comparison to control vaccinated and enzalutamide-treated mice. While anti-PD-1 immune checkpoint inhibition (ICI) alone slowed tumor growth, the majority of vaccinated mice that received anti-PD-1 therapy showed complete tumor elimination. Conclusions: Collectively, these results validate the importance of AR signaling in prostate cancer immune suppression and suggest the potential of AR-V7-specific vaccines as therapeutic strategies against prostate cancer, offering significant protective and therapeutic anti-tumor responses, even in the presence of androgen signaling inhibitors.

Investigation of immunosuppressive treatment compliance, dyspnea, anxiety, and depression levels in lung transplant recipients: online interview.

Following lung transplantation (LTx), it is important for recipients to comply with immunosuppressive treatment and cope with related problems. In the post-LTx period, the course of dyspnea and psychological problems it causes in case of progression are not known. Depression and anxiety may develop in recipients after LTx. However, the relationship between this situation and treatment compliance and dyspnea is uncertain. The aim of this study was to investigate dyspnea, anxiety, and depression levels of recipients following LTx and their immunosuppressive treatment compliance. The study was planned as a descriptive, correlational, and cross-sectional study. Data were collected on various social media platforms via an online interview, and 65 LTx recipients were included in the sample (n = 65). A Participant Information Form, the Modified Borg Scale, the Beck Anxiety Inventory, the Beck Depression Inventory, and the Immunosuppressive Drug Compliance Scale were employed to collect data. The collected data were analyzed using descriptive statistics, the Mann-Whitney U test, and the Kruskal-Wallis test. The mean age of the participants was found to be 52.60 ± 9.44 years, and 56.9% were male. Forty percent of the participants were dependent on oxygen support, and 32.2% had hypertension. Their dyspnea levels were mild, anxiety levels were moderate, depression levels were high, and immunosuppressive treatment compliance levels were slightly above-average. According to the correlation analysis results, dyspnea was associated with anxiety and depression (p < 0.05). As depression increased, immunosuppressive treatment compliance decreased, and the correlation between the two variables was statistically significant (p < 0.05). In this study, as the severity of dyspnea experienced by LTRs increased, the severity of their anxiety and depression also increased. Additionally, there was an inverse correlation between depression and immunosuppressive treatment compliance. LTRs demonstrated insufficient adherence to their immunosuppressive drug regimens, which is very significant in terms of graft survivability. These results suggest that LTRs should be closely monitored at home.

Impact of Immunosuppressants and Vaccination on COVID-19 Outcomes in Autoimmune Patients and Solid Organ Transplant Recipients: A Nationwide Propensity Score-Matched Study.

This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies.

Changes in Medication Adherence Across the Posttransplant Period in Pediatric Organ Transplant Recipients.

Limited research has explored immunosuppressant medication adherence over time in pediatric transplant patients, who often struggle with posttransplant regimen adherence, resulting in poor outcomes. This study investigated the longitudinal growth in immunosuppressive medication levels following transplantation. Medication level variability index (MLVI) scores from tacrolimus blood levels of pediatric organ transplant recipients at a major medical center were analyzed. Linear mixed effect models (LMEM) assessed individual MLVI change trajectories and predictors of growth, exploring both linear and curvilinear growth patterns posttransplant. A sample of 181 patients with at least 4 years of MLVI data were analyzed. Growth curve modeling identified the cubic model as the best fit for the quarterly MLVI values, which significantly decreased within the first 2 years posttransplant before stabilizing. Gender significantly predicted MLVI change, with females showing greater MLVI decreases, while age at transplant did not significantly predict changes. Significant variation in MLVI among individual patients was found in all models. The study demonstrated a significant decrease in MLVI values over time, indicating improved medication adherence in pediatric transplant patients, with females exhibiting more adherent growth patterns than males. Future research should aim to identify pediatric patients at high risk of nonadherence.

Review of Association Between Urinary Tract Infections and Immunosuppressive Drugs after Heart Transplantation.

Management of infections in heart transplant recipients is complex and crucial. In this population, there is a need for a better understanding of immunosuppressive trough levels (C0), infectious complications, and urinary tract infections (UTIs). The purpose of this review was to understand the association between immunosuppressive trough levels and UTIs after heart transplantation. A review of scientific literature (n= 100) was conducted based on the topic of interest by searching PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. The analysis of bacterial pulmonary infection required the occurrence of new or deteriorating pulmonary infiltrates and the development of organisms in cultures of sputum specimens. The diagnosis of UTIs was based on the result of related signs, pyuria, and a positive urine culture. The incidence of UTIs was reported as 0.07 episodes/1000 regarding heart transplantation days. An eightfold increase in the rate of rejection was noted in heart transplant recipients with higher variability in tacrolimus C0. There are associations between C0 of immunosuppressive drugs and clinical presentation of infection complications. Recipients with a low metabolism of immunosuppressive drugs are more susceptible to infectious complications. Attention to the biology of herpes viruses, Escherichia coli, Enterococcus spp., Pseudomonas aeruginosa, and Staphylococcus saprophyticus after heart transplantation are important, in which some of them are the most common pathogens responsible for UTIs. Pneumocystis and cytomegalovirus affect all transplant recipients. Pneumonia due to bacterial, viral, protozoa, and fungal infections, in addition to UTIs, are more specific reported types of infections in heart transplant recipients. Bacterial infections produced by extensively drug-resistant Enterobacteriaceae, vancomycin-resistant enterococci, and non-fermenting gramnegative bacteria were reported to increase after transplantation.

A novel assay to accurately measure TorqueTenovirus load for immunosuppression level monitoring in transplant recipients

A novel assay to accurately measure TorqueTenovirus load for immunosuppression level monitoring in transplant recipients

Outcomes of Pediatric Liver Transplantation in Glycogen Storage Disease Type 1b-A Single-Center Experience.

Liver transplantation (LT) normalizes fasting tolerance in glycogen storage disease type (GSD) 1b. However, reported outcomes post-LT with respect to correction of neutropenia, infection risk and growth are varied. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been recently shown to improve neutropenia in GSD1b patients. In this single-center retrospective study, we reviewed all children who underwent LT for GSD1b. Neutropenia, dose of granulocyte colony-stimulating factor (G-CSF), unplanned hospital attendance, anthropometrics, graft rejection, survival, and the effects of dapagliflozin were analyzed. Data from protocol biopsies obtained at 1, 5, and 10 years post-LT and immunosuppression levels were collected. Eight children (6 female), all on G-CSF pre-transplant, underwent cadaveric LT for GSD1b at median age 3.6 years (IQR 3.3-5.1) with mean follow-up time of 10.3 years (95% CI 7.5-13.1). Neutrophil count and G-CSF requirement did not improve post-LT. Although a reduction in unplanned hospital attendance due to infection (0.98 [95% CI 0.76-1.26] vs. 0.49 [95% CI 0.41 to 0.57] per person-year, p < 0.01) was observed, gastrointestinal complaints and graft dysfunction accounted for a similar hospitalization burden pre- versus post-LT. Body mass index (BMI) reduced post-LT (Z-score 1.47 [95%CI 0.39-2.23] vs. 0.56 [95% CI -0.74 to 1.45], p = 0.02), with no significant change in height. Although all children and grafts have survived, 75% of recipients developed rejection, despite adequate immunosuppression levels, with two children having been found to have developed significant fibrosis on their 5-year protocol biopsy. Although dapagliflozin allowed cessation of G-CSF, no improvement in neutrophil count was observed. Despite this, a reduction in gastrointestinal and infection-related morbidity was noted following dapagliflozin. Although LT normalizes fasting tolerance in GSD1b and reduces hospital attendance due to infection, morbidity from infection and gastrointestinal manifestations persist. Children in our cohort experienced high rates of rejection necessitating titration of immunosuppression to balance risk of infection against organ rejection. Future studies should investigate whether early introduction of SGLT2 inhibitors post-LT impact morbidity in this group.

Establishment of a prognostic model for pancreatic cancer based on mitochondrial metabolism related genes

AimPancreatic ductal adenocarcinoma (PAAD) is recognized as an exceptionally aggressive cancer that both highly lethal and unfavorable prognosis. The mitochondrial metabolism pathway is intimately involved in oncogenesis and tumor progression, however, much remains unknown in this area. In this study, the bioinformatic tools have been used to construct a prognostic model with mitochondrial metabolism-related genes (MMRGs) to evaluate the survival, immune status, mutation profile, and drug sensitivity of PAAD patients.MethodUnivariate Cox regression and LASSO regression were used to screen the differentially expressed genes (DEGs), and multivariate Cox regression was used to develop the risk model. Kaplan–Meier estimator was employed to identify MMRGs signatures associated with overall survival (OS). ROC curves were utilized to evaluate the model's performance. Maftools, immunedeconv and CIBERSORT R packages were applied to analyze the gene mutation profiles and immune status. The corresponding sensitivity to pharmaceutical agents was assessed using oncoPredict R packages.ResultsA prognostic model with five MMRGs was developed, which defined the patients as high-risk showed lower survival rates. There was good consistency among individuals categorized as high-risk, showing elevated rates of genetic alterations, particularly in the TP53 and KRAS genes. Furthermore, these patients exhibited increased levels of immunosuppression, characterized by an increased presence of macrophages, neutrophils, Th2 cells, and regulatory T cells. Additionally, high-risk patients showed increased sensitivity to Sabutoclax and Venetoclax.ConclusionBy utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients.

Impact of HLA Alleles on COVID-19 Severity in Kidney Transplant Recipients: A Single-Center Study.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has significantly impacted global health, particularly affecting vulnerable populations, such as organ transplant recipients. Human leukocyte antigens (HLAs) play a critical role in immune response regulation, and understanding their association with COVID-19 can provide insights into disease susceptibility and severity. This study aims to explore the association between HLA allele variability and COVID-19 susceptibility and severity among kidney transplant recipients. Methods In 2023, we conducted a study on 73 kidney transplant recipients who tested positive for COVID-19 via polymerase chain reaction. This study included assessments of clinical status, immunosuppressive drug levels, HLA allele frequencies, and donor-recipient tissue compatibility. Molecular analyses were performed using sequence-specific oligonucleotide typing, and statistical analysis was conducted using IBM SPSS Statistics, version 20.0 (IBM Corp., Armonk, NY). Results Among the participants, 31 were hospitalized and 42 were treated as outpatients. Significant differences were observed in HLA allele distributions, particularly the HLA-A*11 allele, which was more prevalent in outpatient-treated patients, suggesting a potential protective effect. No significant age differences were observed between hospitalized and outpatient groups. Serum tacrolimus levels were notably higher in outpatients. Statistical analyses revealed significant associations between certain HLA groups and the severity of COVID-19 infection. Conclusions This study highlights the importance of HLA allele compatibility in influencing the clinical outcomes of COVID-19 in kidney transplant recipients. The findings suggest that specific HLA alleles may reduce susceptibility or moderate the severity of COVID-19, indicating a need for broader genetic studies across diverse populations to validate these observations and improve management strategies for transplant recipients during pandemics.

Tomato Spotted Wilt Virus Suppresses the Antiviral Response of the Insect Vector, Frankliniella occidentalis, by Elevating an Immunosuppressive C18 Oxylipin Level Using Its Virulent Factor, NSs.

Orthotospovirus tomatomaculae (tomato spotted wilt virus, TSWV) is transmitted by the western flower thrips, Frankliniella occidentalis. Epoxyoctadecamonoenoic acids (EpOMEs) function as immune-suppressive factors, particularly in insects infected by viral pathogens. These oxylipins are produced by cytochrome P450 monooxygenases (CYPs) and are degraded by soluble epoxide hydrolase (sEH). In this study, we tested the hypothesis that TSWV modulates the EpOME level in the thrips to suppress antiviral responses and enhance its replication. TSWV infection significantly elevated both 9,10-EpOME and 12,13-EpOME levels. Following TSWV infection, the larvae displayed apoptosis in the midgut along with the upregulated expression of four caspase genes. However, the addition of EpOME to the viral treatment notably reduced apoptosis and downregulated caspase gene expressions, which led to a marked increase in TSWV titers. The CYP and sEH genes of F. occidentalis were identified, and their expression manipulation using RNA interference (RNAi) treatments led to significant alternations in the insect's immune responses and TSWV viral titers. To ascertain which viral factor influences the host EpOME levels, specialized RNAi treatments targeting genes encoded by TSWV were administered to larvae infected with TSWV. These treatments demonstrated that NSS expression is pivotal in manipulating the genes involved in EpOME metabolism. These results indicate that NSs of TSWV are crucially linked with the elevation of host insect EpOME levels and play a key role in suppressing the antiviral responses of F. occidentalis.

No increased risk of tuberculosis-related immune reconstitution inflammatory syndrome with integrase inhibitor-based antiretroviral therapy in people with HIVwith profound immunosuppression.

The issue of whether integrase inhibitors (INSTIs) may confer a higher risk of paradoxical tuberculosis-related immune reconstitution inflammatory syndrome (TB-IRIS) compared with other classes of antiretroviral in people with HIV with a profound level of immunosuppression remains insufficiently explored. We aimed to assess whether such a higher risk exists by examining a cohort of patients with TB-HIV initiating antiretroviral therapy (ART) in Hong Kong. This was a retrospective review of 133 patients registered in the TB-HIV Registry of the Department of Health during the period 2014-2021. Sixteen of 70 patients (22.9%; 95% confidence interval [CI] 13.0-32.7) and 14 of 63 patients (22.2%; 95% CI 12.0-32.5) from the INSTI and non-INSTI groups experienced TB-IRIS (p = 0.920). The median intervals between ART initiation and IRIS among patients from the two groups were similar (3 weeks [interquartile range IQR 2.0-7.8] vs. 4 weeks [IQR 2.0-5.1], p = 0.620). The proportion of patients requiring steroid therapy were similar, as were the hospitalization rates. There was no IRIS-related death in either group. The risk of TB-IRIS with INSTI versus non-INSTI was also similar in a stratified analysis in a subgroup of patients with a baseline CD4 count of <50 μL (10/33 [30.3%; 95% CI 14.6-46.0] vs. 10/22 [45.5%; 95% CI 24.7-66.3], p = 0.252) and another subgroup of patients with ART initiated within 4 weeks of anti-TB treatment (10/26 [38.5%; 95% CI 19.8-57.2] vs. 10/23 [43.5%; 95% CI 23.2-63.7], p = 0.721). Our cohort study did not offer support for an increased risk of TB-IRIS with INSTIs compared with non-INSTIs, even in severely immunocompromised people with HIV.

Porokeratoses: an update on pathogenesis and treatment.

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second-hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%-16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging.

Dried Blood Spot Sampling for Monitoring Children With Immune-Mediated Glomerulopathies and After Kidney Transplantation

BackgroundMonitoring kidney function and immunosuppressant levels in children post-kidney transplantation or those with glomerulopathies is challenging due to frequent venipunctures and clinic visits. Capillary dried blood spot sampling (DBS) offers a potential alternative. MethodsIn this prospective single-center study, 89 children (38 % female, 62 % male) requiring therapeutic drug monitoring (TDM) and kidney function assessment were enrolled. 79 % of the patients were kidney transplant recipients, and 21 % suffered from immune-mediated glomerulopathies. The mean age was 13.4 years (range 5.7-18.0). DBS and standard venous serum samples were collected simultaneously for tacrolimus (TAC), cyclosporine A (CsA), everolimus (EVR), and creatinine levels. Further, patient feedback on pain perception and feasibility was collected via questionnaire. ResultsNo significant differences in parameter values between DBS and standard methods were found (creatinine -1.7±14.5 μmol/l; EVR 0.1±1.2 μg/L; TAC 0.3±1.1μg/L; CsA 2.8±9.8 μg/L). DBS demonstrated sufficient accuracy compared to standard methods. Patients favored DBS and telehealth consultations, especially due to less travel and school absences. Patients preferred finger pricking over ear pricking. ConclusionsCapillary DBS proves reliable for TDM and kidney function assessment in pediatric kidney disease. It reduces patient and family burden compared to venous blood collection, while also enabling telehealth consultations.

Preparing the Heart for a New Baby: Management of Pregnancy in Heart Transplant Recipients.

Heart transplant (HT) recipients are more frequently reaching childbearing age given improvement in median survival and outcomes after HT. Although most pregnancies in HT recipients have favorable outcomes, poor fetal outcomes and maternal complications such as hypertensive disorders of pregnancy are more common in HT recipients than in the general population. In this review, we summarize the current evidence to guide the management of pregnancy in HT recipients. Preconception counseling, focused on risk stratification and optimal timing of conception, is the first important step to optimize pregnancy outcomes. During pregnancy and in the postpartum period, frequent monitoring of graft function and immunosuppressive levels is recommended. Calcineurin inhibitors and corticosteroids should be the mainstay of treatment for both prevention and treatment of graft rejection. Delivery planning should follow usual obstetric indications, preferably with vaginal delivery at term using regional anesthesia. A multidisciplinary care team should be involved in management through all stages of pregnancy to ensure success.

CD73 Is an Immunometabolic Biomarker of Poor Prognosis in Patients With Primary Cutaneous Squamous Cell Carcinoma and Hematologic Malignancy.

Impaired immunity may drive the increased incidence and aggression of cutaneous squamous cell carcinoma (cSCC) in patients with hematologic malignancy; however, precise mechanisms and prognostic biomarkers remain undefined. CD73 maintains elevated immunosuppressive adenosine levels and is associated with poor prognosis in several tumor microenvironments. Identify poor outcome biomarkers in patients with cSCC and hematologic malignancy. Differentially expressed genes in tumors from patients with hematologic malignancy experiencing good ( n = 8) versus poor ( n = 7) outcomes were identified by NanoString analysis. Results were validated at the protein level using CD73 immunohistochemistry in cSCC patients with ( n = 38) and without ( n = 29) hematologic malignancy. Forty-eight genes were differentially expressed in tumors from patients with hematologic malignancy experiencing good versus poor outcomes. CD73 gene expression was >2-fold higher in patients with poor versus good outcomes or normal skin. Significantly increased CD73 protein levels were observed in cSCC tumors with poor versus good outcomes from patients with hematologic malignancies ( p < .01), whereas no differences were noted in tumors with poor versus good outcomes from patients without hematologic malignancies ( p = .49). CD73 is highly expressed in poor prognosis cSCC from patients with hematologic malignancy and may represent a useful biomarker and potential therapeutic target.