Therapeutic efficacy and safety of JAK inhibitors in treating polymyositis/dermatomyositis: a single-arm systemic meta-analysis.

Introduction: We performed a single-arm meta-analysis to evaluate the efficacy and safety of JAK inhibitors in the treatment of dermatomyositis (DM)/ polymyositis (PM). Methods: Relevant studies from four databases were systematically searched until April 25, 2023. The primary endpoint was Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) and other outcomes were Manual Muscle Testing (MMT) and Creatine Kinase (CK). According to the type of JAK and medication regimen, we conducted subgroup analyses. The registration number in PROSPERO was CRD42023416493. Results: According to the selection criteria, we identified 7 publications with a total of 91 patients. Regarding skin lesions, the CDASI decreased by 17.67 (95% CI: -20.94 ~ -14.41). The CK increased by 8.64 U (95% CI: -28.25 ~ 45.53). About muscle lesions, MMT increased by 10.31 (95% CI: -2.83 ~ 23.46). Subgroup analysis revealed that different types of JAK inhibitors had various degrees of reduction. CDASI in patients treated with RUX had the lowest one [-20.00 (95% CI: -34.9 ~ -5.1)], followed by TOF [-18.29 (95% CI: -21.8 ~ -14.78)] and BAR [-11.2 (95% CI: -21.51 ~ -0.89)]. Additionally, the mean reduction in CDASI in patients treated with TOF alone was 16.16 (95% CI: -21.21 ~ -11.11), in combination with other immunosuppressants was 18.59 (95% CI: -22.74 ~ -14.45). For safety evaluation, one patient developed Orolabial HSV, and two patients developed thromboembolism events. Discussion: In summary, this meta-analysis demonstrated that JAK inhibitors can potentially treat DM/PM without severe adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42023416493, identifier CRD42023416493.

Long-term outcomes of two-dose alemtuzumab induction in pediatric kidney transplantation.

BACKGROUND: Alemtuzumab is a lymphocyte depleting agent used for induction in kidney transplant, but long-term information on its use in pediatric recipients remains sparse. METHODS: We performed a single-center retrospective cohort study of 57 pediatric kidney transplant recipients receiving alemtuzumab 20 mg/m2/dose ×2 doses for induction immunosuppression. All patients underwent surveillance biopsies, and 91.3% underwent steroid withdrawal by day 4 post-transplant. Outcomes of interest included graft survival, development of donor specific antibodies (DSA), incidence of viremia and PTLD, and duration of lymphopenia. RESULTS: Median follow-up time was 7.9 years (IQR 5-13.6 years). Median graft survival was 16.5 years (95% CI 11.6-unknown). DSA developed in 36.5% at a median of 944 days (IQR 252-2113 days). Incidences of BK polyomavirus DNAemia (BKPyV-DNAemia), CMV DNAemia, and EBV DNAemia were 38.6%, 22.8%, and 14%, respectively; one patient developed PTLD at 13.3 years post-transplant. Median duration of lymphopenia was 365 days (IQR 168-713 days); 19.3% of patients remained lymphopenic at 3 years post-transplant. There was no association between duration of lymphopenia and graft survival, rejection, DSA detection, or viremia. CONCLUSIONS: A two-dose alemtuzumab induction protocol can have excellent outcomes with a steroid-free maintenance immunosuppression regimen. More comprehensive, multicenter, comparative studies of pediatric kidney transplant are needed to improve long-term outcomes.

SLESIS-R: an improved score for prediction of serious infection in patients with systemic lupus erythematosus based on the RELESSER prospective cohort.

OBJECTIVE: To develop an improved score for prediction of severe infection in patients with systemic lupus erythematosus (SLE), namely, the SLE Severe Infection Score-Revised (SLESIS-R) and to validate it in a large multicentre lupus cohort. METHODS: We used data from the prospective phase of RELESSER (RELESSER-PROS), the SLE register of the Spanish Society of Rheumatology. A multivariable logistic model was constructed taking into account the variables already forming the SLESIS score, plus all other potential predictors identified in a literature review. Performance was analysed using the C-statistic and the area under the receiver operating characteristic curve (AUROC). Internal validation was carried out using a 100-sample bootstrapping procedure. ORs were transformed into score items, and the AUROC was used to determine performance. RESULTS: A total of 1459 patients who had completed 1 year of follow-up were included in the development cohort (mean age, 49±13 years; 90% women). Twenty-five (1.7%) had experienced ≥1 severe infection. According to the adjusted multivariate model, severe infection could be predicted from four variables: age (years) ≥60, previous SLE-related hospitalisation, previous serious infection and glucocorticoid dose. A score was built from the best model, taking values from 0 to 17. The AUROC was 0.861 (0.777-0.946). The cut-off chosen was ≥6, which exhibited an accuracy of 85.9% and a positive likelihood ratio of 5.48. CONCLUSIONS: SLESIS-R is an accurate and feasible instrument for predicting infections in patients with SLE. SLESIS-R could help to make informed decisions on the use of immunosuppressants and the implementation of preventive measures.

COVID-19 and renal allograft rejection: insight from controlled and non-controlled studies.

AIM: Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). METHODS: This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: 'COVID', 'Renal', 'Kidney', 'Transplant', and 'Rejection'. The results from controlled and uncontrolled studies were separately collated and analyzed. RESULTS: A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. CONCLUSION: In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival.

Pancreatic cancer is an aggressive disease with a 5 year survival rate of 13%. This poor survival is attributed, in part, to limited and ineffective treatments for patients with metastatic disease, highlighting a need to identify molecular drivers of pancreatic cancer to target for more effective treatment. CD200 is a glycoprotein that interacts with the receptor CD200R and elicits an immunosuppressive response. Overexpression of CD200 has been associated with differential outcomes, depending on the tumor type. In the context of pancreatic cancer, we have previously reported that CD200 is expressed in the pancreatic tumor microenvironment (TME), and that targeting CD200 in murine tumor models reduces tumor burden. We hypothesized that CD200 is overexpressed on tumor and stromal populations in the pancreatic TME and that circulating levels of soluble CD200 (sCD200) have prognostic value for overall survival. We discovered that CD200 was overexpressed on immune, stromal, and tumor populations in the pancreatic TME. Particularly, single-cell RNA-sequencing indicated that CD200 was upregulated on inflammatory cancer-associated fibroblasts. Cytometry by time of flight analysis of PBMCs indicated that CD200 was overexpressed on innate immune populations, including monocytes, dendritic cells, and monocytic myeloid-derived suppressor cells. High sCD200 levels in plasma correlated with significantly worse overall and progression-free survival. Additionally, sCD200 correlated with the ratio of circulating matrix metalloproteinase (MMP) 3: tissue inhibitor of metalloproteinase (TIMP) 3 and MMP11/TIMP3. This study highlights the importance of CD200 expression in pancreatic cancer and provides the rationale for designing novel therapeutic strategies that target this protein.

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies.

Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation's delicate balance, spanning innate and adaptive immunity. Viral factors' disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation's impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.

Adaptative Strategy of Immunosuppressive Drugs Dosage Adjustments When Combined With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients With COVID-19.

Nirmatrelvir/ritonavir is a promising option for preventing severe COVID-19 in solid organ transplant recipients with SARS-CoV-2 infection. However, concerns have arisen regarding potential drug interactions with calcineurin inhibitors (CNI). This two-phase multicentre retrospective study, involving 113 patients on tacrolimus and 13 on cyclosporine A, aimed to assess the feasibility and outcomes of recommendations issued by The French societies of transplantation (SFT) and pharmacology (SFPT) for CNI management in this context. The study first evaluated adherence to recommendations, CNI exposure, and clinical outcomes. Notably, 96.5% of patients on tacrolimus adhered to the recommendations, maintaining stable tacrolimus trough concentrations (C0) during nirmatrelvir/ritonavir treatment. After reintroduction, most patients experienced increased C0, with 42.9% surpassing 15 ng/mL, including three patients exceeding 40 ng/mL. Similar trends were observed in cyclosporine A patients, with no COVID-19-related hospitalizations. Moreover, data from 22 patients were used to refine the reintroduction strategy. Modelling analyses suggested reintroducing tacrolimus at 50% of the initial dose on day 8, and then at 100% from day 9 as the optimal approach. In conclusion, the current strategy effectively maintains consistent tacrolimus exposure during nirmatrelvir/ritonavir treatment, and a stepwise reintroduction of tacrolimus may be better suited to the low CYP3A recovery.

Clinicopathological features and outcome of secondary steroid resistant nephrotic syndrome: A retrospective analysis.

Objective: To determine the clinico-pathological features and long-term outcome of secondary steroid-resistant nephrotic syndrome treated with steroids and calcineurin inhibitors. METHODS: The retrospective cohort study was conducted at the Sindh Institute of Urology and Transplant, Karachi, in June and July 2023, and comprised data from January 1, 2008, to December 31, 2020, of children aged 1-18 years who developed steroid resistance after initial sensitivity to steroids with at least 1-year of follow-up. Demographics as well as time taken to secondary steroid response were documented. Renal biopsy of all patients with secondary steroid resistance had been performed. Eventual outcomes after treatment with calcineurin inhibitors based on the degree of proteinuria and serum albumin levels were used to categorise complete remission, partial remission and no response. Kidney function, as determined by estimated glomerular filtration rate, was recorded. Data was analysed using SPSS 22. RESULTS: Of the 1,000 patients who underwent renal biopsy for steroid resistance, 48(4.8%) had idiopathic steroid-resistant nephrotic syndrome; 32(66.7%) males, 16(33.3%) females and median age of 5 years (interquartile range: 4-7.3 years). Median age at diagnosis of nephrotic syndrome was 5 years (interquartile range: 3.6-7.3 years). The median time from nephrotic syndrome to secondary steroid-resistant nephrotic syndrome was 23 months (interquartile range: 8.75-44.5 months). Biopsy results at diagnosis showed that 27(56.3%) had minimal change disease. The mean follow-up time was 6.1±3.2 years. Of the 43(89.5%) patients who received cyclosporin for 1 year, 29(67%) obtained complete remission, 5(12%) attained partial remission and no response was seen in 9(21%) patients. Conclusion: Majority of the children had minimal change disease at the time of diagnosis of secondary steroid-resistant nephrotic syndrome. The long-term response with calcineurin inhibitors was favourable at 1 year.

Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

Efficacy and safety of immunosuppressive therapy combined with eltrombopag for severe aplastic anemia: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA. METHODS: We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis. RESULTS: A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics. CONCLUSION: EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.

Clinicopathological correlation of patients with lupus nephritis: Data from a tertiary center in Saudi Arabia.

Systemic lupus erythematosus mainly affects young women, and approximately half of systemic lupus erythematosus patients develop lupus nephritis (LN). However, data on the types and remission rates of LN in Saudi Arabia are limited. Therefore, we aimed to highlight the LN remission rates in our population. A retrospective record review was conducted between January 2007 and December 2020 in a tertiary center in the western region of Saudi Arabia to determine the remission rates among patients with biopsy-proven LN who met the EULAR\ACR 2019 classification criteria. We identified 59 patients with biopsy-proven LN, mostly in young women. The common histopathological pattern was Class IV LN in 26 patients (44%). Three induction protocols were identified, along with systemic steroids: the high-dose cyclophosphamide protocol in 21 patients (35.6%), low-dose protocol in 4 patients (6.8%), and mycophenolate mofetil (MMF) in 41 patients (69.5%). Partial response, defined as the reduction of the 24-hour proteinuria by 25% at 3 months and 50% at 6 months, was achieved in 18 patients (33.3%) at 3 months and decreased to 13 patients (24.1%) at 6 months. Complete clinical response, defined as 24-hour urinary protein between 500 and 700 mg at 12 months, was achieved in 44 patients (81.5%). Complete remission was higher among patients with Class IV LN (64.4%). The achievement of partial clinical response at 3 months was significantly lower among patients with hypertension (P = .041). This study presented the LN remission rates in a single center in Saudi Arabia. Similar to previous studies, Class IV LN were the most common histopathological finding in this study. Complete remission at 12 months was achieved in 44 (81%) patients. Delayed remission is associated with hypertension at the time of LN diagnosis.

Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.

OBJECTIVES: Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. METHODS: Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. RESULTS: A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. CONCLUSION: Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Effect of education on sun-safe behaviour in kidney transplant recipients.

BACKGROUND: Organ transplant recipients (OTR) are more likely to develop skin cancer than the general population. One of the main components of the exposome that triggers the development of skin tumours is solar ultraviolet (UV) radiation. To reduce the incidence of harmful consequences of sun exposure, sun protection education is needed for patients taking long-term immunosuppressive drugs. METHODS: In a previous study, we assessed the sun-safe behaviour of 221 OTR using a questionnaire before and after transplantation and personally educated the patients about proper sun protection. After the education, there were no further reminder presentations. Presently, the sun protection and sun seeking habits of the available 176 of these patients were questioned to assess the long-term effect of the previous sun protection education. RESULTS: Two-four years after the education, more patients wore hats and protected their skin with long-sleeved clothing than before the education. In terms of sun seeking habits, both occupational and recreational sun exposure decreased significantly. Significantly fewer people went on holiday after transplantation, but those who went on holiday spent significantly less time in the sun. CONCLUSION: The long-term positive effects of education can be seen both in the patients' sun protection and in their sun seeking habits. However, the long-term goal is to maintain these results and thereby reduce the likelihood of skin tumours and consequently the associated tumour death.

A new definition and treatment options of allergic alveolitis.

In this review, we discuss a new definition and treatment options of allergic alveolitis (AA). AA is an immune-mediated interstitial lung disease triggered by inhaled antigens, it is defined as non-fibrotic (inflammatory) and/or fibrotic, and diagnosis relies on a multidisciplinary approach using clinical, radiological and sometimes histological assessments. Treatment involves early antigen elimination and may include corticosteroids or other immunosuppressants. Prognosis varies from reversible inflammation to irreversible fibrosis. Early detection is crucial for better outcomes.

Analysis of belimumab prescription and outcomes in a 10-year monocentric cohort: is there an advantage with early use?

OBJECTIVE: The objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus (SLE). METHODS: This is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit. RESULTS: From 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years. CONCLUSIONS: Our data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.