Immunosuppressive Medications Research Articles

Comparison of clinical outcomes of pulmonary nocardiosis between AIDS and non-AIDS patients

BackgroundNocardia species can affect both immunocompetent and immunocompromised people.MethodThis retrospective study, from 2009 to 2022, aims to compare the survival analyses of pulmonary nocardiosis in AIDS and non-AIDS patients in northeastern Thailand.ResultsA total of 215 culture-confirmed cases of pulmonary nocardiosis: 97 with AIDS and 118 without AIDS. The median CD4 count of AIDS patients was 11 cells/µL (range: 1–198), and 33% had concurrent opportunistic infections. 63.6% of 118 non-AIDS patients received immunosuppressive medications, 28.8% had comorbidities, and 7.6% had no coexisting conditions. Disseminated nocardiosis and pleural effusion were more prevalent among AIDS patients, whereas non-AIDS patients revealed more shock and respiratory failure. One hundred-fifty patients underwent brain imaging; 15 (10%) had brain abscesses. Patients with pulmonary nocardiosis have overall 30-day and 1-year mortality rates of 38.5% (95% CI: 32.3%, 45.4%) and 52.1% (95% CI: 45.6%, 58.9%), respectively. The Cox survival analysis showed that AIDS patients with disseminated nocardiosis had a 7.93-fold (95% CI: 2.61–24.02, p < 0.001) increased risk of death within 30 days compared to non-AIDS patients when considering variables such as age, Charlson comorbidity index, concurrent opportunistic infections, duration of illness, shock, respiratory failure, multi-lobar pneumonia, lung abscesses, and combination antibiotic therapy. While AIDS and pulmonary nocardiosis had a tendency to die within 30 days (2.09 (95% CI, 0.74–5.87, p = 0.162)).ConclusionAIDS with pulmonary nocardiosis, particularly disseminated disease, is a serious opportunistic infection. Early diagnosis and empiric treatment with a multidrug regimen may be the most appropriate approach in a resource-limited setting.

MIS-C Treatment: Is glucocorticoid monotherapy enough for mild cases?

BackgroundThe effectiveness of using only glucocorticoids (GCs) in mild multisystem inflammatory syndrome (MIS-C) cases was compared with combined treatment [GCs + Intravenous immune globulin (IVIG)]. MethodsThis retrospective cohort study was conducted between June 1, 2020, and June 1, 2022, in a tertiary care center in Istanbul, Turkey. Clinical and investigational data of the MIS-C patients were analyzed. The patients were divided into two groups: those who received only GCs and those who received the GCs + IVIG combination. The primary outcome focused on assessing the deterioration of the patient's clinical condition, the occurrence of shock, admission to the pediatric intensive care unit (PICU), and the need for additional immunosuppressive medication. Secondary outcomes included evaluating the course of cardiovascular and infection-related complications observed at the one-year follow-up. ResultsNinety-seven MIS-C patients with a median age of 41 (3‐ 214) months were enrolled. Fifty-six (57.7%) patients were male. All the patients had fever at admission with a temperature of 39 °C (37.5 °C–40.1 °C). Thirty-two patients (33%) had cardiac findings on echocardiography [left ventricular dysfunction (n= 13, 13.5%), coronary artery involvement (n= 11, 11.3%), and dilation of cardiac cavities and/or increased cardiac muscle thickness (n= 8, 8.2%)]. Thirteen patients (13.5%) required intensive care. All patients received GCs [only GCs (group I; n= 65, 67%)], and 32 patients (33%) with severe manifestations and/or cardiac involvement received GCs + IVIG (group II). No mortality was observed. None of the patients had any complaints at the one-year follow-up, and all echocardiography findings were normal. ConclusionThis study provides preliminary evidence that GC monotherapy is a safe treatment alternative for mild MIS-C cases without cardiac involvement.

Pharmacotherapy of autoimmune rheumatic diseases – from monoclonal antibodies to CAR T cells: 20 years later

Autoimmunity is a pathological process associated with a violation of immunological tolerance to normal structural components of the body (autoantigens), associated with the predominance of active (adaptive) immunity and manifested by hyperproduction of autoantibodies. Systemic autoimmune rheumatic diseases (SARDs) are among the most common and severe nosological forms of this pathology associated with autoimmunity. Problems of pharmacotherapy of SARDs are the subject of intensive research. At the beginning of the 21st century, more than 20 biologic agents were developed for the treatment of rheumatoid arthritis – monoclonal antibodies (mAbs) and recombinant proteins that control inflammation associated with the overproduction of “pro-inflammatory” cytokines, the use of which has dramatically improved the results of pharmacotherapy. However, much less research has been devoted to studying the possibilities of pharmacotherapy aimed at selective suppression of the “autoimmune” component of the pathogenesis of SADRs associated with uncontrolled activation of B cells and restoration of immunological tolerance to autoantigens. In the spectrum of drugs whose mechanism of action is associated with the suppression of pathological activation of B cells, the leading place is occupied by rituximab (RTM). It is noteworthy that 20 years ago (2004), a group of researchers led by prof. J.C. Edwards first demonstrated the effectiveness of RTM in patients with RA, which was soon successfully repositioned to treat a wide range of SARDs. A major achievement in the pharmacotherapy of SARDs is associated with the use of CAR (сhimeric antigen receptor) T cell therapy, developed for the treatment of refractory hematological tumors. The main component of CART-cells is a genetically engineered T-cell receptor that recognizes the target antigen without the participation of the major histocompatibility complex. Although limited, extremely impressive data regarding high remission rates have been obtained by adapting CD19 CART-cell therapy to treat patients with severe systemic lupus erythematosus (SLE) and other SARDs refractory to standard immunosuppressive medications. The article discusses the results of the use of CART-cell therapy in SLE and other SARDs and prospects for further research.

Long-term graft survival in a kidney transplant recipient with glioblastoma: Case report

Long-term immunosuppression after transplantation can increase the risk of cancer development in recipient patients. This case report describes the treatment approach for glioblastoma in a kidney transplant recipient after transplantation. The patient, a 61-year-old woman, received a living donor kidney transplant 24 years ago due to congenital nephrotic syndrome. The patient was on various immunosuppressive medications, including cyclosporine, prednisolone, and mycophenolate mofetil.After 16 years of follow-up, the patient presented with symptoms of brain tumor, leading to further tests. Subsequent examination revealed the presence of a tumor that had spread to frontal region within the brain.A surgical procedure was subsequently conducted to extract the tumor cells and alleviate the resulting pressure within the brain. Based on pathology results, it was determined that the patient had glioblastoma.Methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was detected, indicating the potential response to chemotherapy. Chemotherapy was initiated, along with radiation therapy.After the diagnosis and surgery, the patient's medications for the kidney transplant were modified. Rapamycin replaced the previous medications, and the dose of mycophenolate mofetil and prednisolone was decreased. After 7 years, the patient's kidney is functioning well, with a creatinine level of 1.5, and brain imaging showed no abnormalities. After kidney transplantation, there is an increased risk of various cancers.Overall, this case report demonstrates a successful treatment approach for glioblastoma after kidney transplantation, emphasizing the need for close monitoring and individualized management in transplant recipients at risk for cancer development.Considering the current stability of the patient's condition after a change in medication regimen, patients who have been using the drug Cyclosporine for a long time should be included in future evaluations due to its carcinogenic properties.

Study protocol for the development and validation of a questionnaire evaluating predisposition to immunosuppressant medication non-adherence of kidney pre-transplant patients. The KATITA project.

Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.

Updates in the Management of Giant Cell Arteritis.

To briefly review the latest updates in management in giant cell arteritis, an autoimmune vasculitis affecting the medium to large vessels. Here, we review the known and newer trends in management of giant cell arteritis. While high dose glucocorticoids remain the mainstay of therapy, immunosuppressive medications are increasingly utilized to reduce the burden and risk of long-term glucocorticoid use. Published guidelines by the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) suggest early use of steroid-sparing immunosuppressive medications in patients with recently diagnosed or relapsing giant cell arteritis. Immunosuppressive medications include oral small molecules such as methotrexate and leflunomide and biologics, including the recently Federal Drug Administration (FDA) approved tocilizumab. Glucocorticoids remain the cornerstone of management for newly diagnosed disease but with the increasing use of medications such as IL-6 inhibitors, patients are decreasing steroid use within weeks, thereby limiting risks associated with long-term steroid use.

Effect of antimetabolite regimen on cellular and humoral immune response to SARS-COV-2 vaccination in solid organ transplant recipients

ObjectiveNovel mRNA-based vaccines have been proven to be powerful tools in combating the global pandemic caused by SARS-CoV-2 protecting individuals, especially the immunocompromised, from COVID-19. Still, it remains largely unknown how solid organ transplant and different immunosuppressive medications affect development of vaccine-induced immunity. MethodsIn this work, we monitored humoral and cellular memory responses after mRNA SARS-CoV-2 two-doses and booster doses vaccination in cystic fibrosis lung transplanted patients (CFT) and compared them with both cystic fibrosis patients without lung transplant (CF) and with kidney transplant recipients (KT). In particular, we investigated the effects of immunosuppressive regimens on immune memory to SARS-CoV-2 after mRNA SARS-CoV-2 vaccine in transplanted patients. ResultsOur results showed that immunocompromised transplanted patients displayed a weak cellular and humoral memory to SARS-CoV-2 mRNA vaccination. In addition, obtained data clearly demonstrate that immunosuppressive therapy regimen including antimetabolites, further reduces patients’ ability to respond to vaccination at both humoral and cell-mediated level. Notably, patient treated with antimetabolites showed a lower humoral and cellular response also after a booster dose vaccination. ConclusionThese results, even if obtained on a small patient's cohort, question whether immunocompromised patients need interventions to improve vaccine SARS-CoV-2 mRNA vaccine response such as additional jab or modulation of immunosuppressive therapy.

Treatment of oral graft-versus-host disease with intraoral nbUVB phototherapy.

There are limited treatment options available for hematopoietic stem-cell transplant patients (HSCT) with oral graft-versus-host disease (GVHD). Intraoral phototherapy is a novel, yet promising therapeutic regimen. To assess the safety and effectiveness of intraoral narrowband UVB (nbUVB) phototherapy in the treatment of oral GVHD. This case series evaluated 10 patients with refractory oral GVHD, who were treated at Northwestern Memorial Hospital with nbUVB between July 2019 and October 2023. Primary outcomes were to evaluate the safety and efficacy of phototherapy. Efficacy was measured by objective improvement in symptom scores and subjective improvement in patient reported symptoms. Safety was determined by the withdrawal due to adverse events. Total nbUVB exposure, number of treatments, and change in systemic immunosuppressive medications were also examined. The study cohort comprised 10 patients who developed oral GVHD at a median of 9.5months after HSCT. The total median dose of nbUVB was 36J/cm2, and the median number of sessions was 55. All 10 patients demonstrated some degree of improvement in symptoms. Notably, there was a reduction in the number of patients who reported symptoms of oral pain (83%), bleeding (67%), xerostomia (50%), and oral sensitivity (78%) after initiating phototherapy. There was also a statistically significant decrease in the levels of pain, erythema, and edema (p ≤ 0.001, < 0.001, 0.01, respectively). Most patients tolerated phototherapy well, but 1 patient withdrew from treatment due to adverse effects. Seventy-five percent of patients who were on immunosuppressive medications were able to decrease or stop these medications. This case series suggests that nbUVB phototherapy is well tolerated and efficacious in patients with oral GVHD.

Interactions of TTV with BKV, CMV, EBV, and HHV-6A and their impact on post-transplant graft function in kidney transplant recipients.

Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. TTV had the highest prevalence and viral loads at 100% and a mean of 5.72 copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0 cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6 months after transplant. We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.

Recurrence of autoimmune liver diseases after liver transplantation: Review and expert opinion statement.

Autoimmune liver diseases (AILDs) constitute the fourth most common indication for liver transplantation (LT) across the world. In general, the outcomes after LT are acceptable; however, disease recurrence after LT is common for all AILD, which can negatively affect graft and overall survival. Several questions persist, including the risk factors associated with recurrent disease, optimal antirejection medications, strategies to reduce the risk of recurrence, and how to best incorporate these strategies into clinical practice. For that reason, we assembled an international group of experts to review evidence to address these outstanding questions regarding LT for AILD. Survival rates after LT are ~90% and 70% at 1 and 5 years, and recurrent disease occurs in 10%-50% of patients with AILD. In patients with disease recurrence, graft survival decreased by 18% and 28% and overall survival by 8% and 12% at 5 and 10 years after LT, respectively. Recurrent autoimmune hepatitis is associated with high aminotransferases and immunoglobulin G (IgG) before LT, lymphoplasmacytic infiltrates in the explants, and may be associated with the absence of steroids after LT. However, the efficiency and safety of triple immunosuppressive maintenance therapy is still debatable. Younger age at diagnosis with primary biliary cholangitis or LT is associated with primary biliary cholangitis recurrence. Preventive use of ursodeoxycholic acid reduces the risk of recurrence and has a benefit in graft and patient survival. Episodes of systemic inflammation, including T-cell-mediated rejection, active ulcerative colitis, and episodes of cholangitis, are associated with recurrent PSC. Recurrent disease for AILD is associated with worse graft and patient survival. Patients with autoimmune hepatitis could be considered for long-term low-dose predniso(lo)ne, whereas patients with primary biliary cholangitis should be placed on preventive ursodeoxycholic acid after LT. There are no specific treatments for PSC recurrence; however, adequate control of inflammatory bowel disease and optimal immunosuppression to avoid T-cell-mediated rejection should be encouraged.

The American Association of Tissue Banks tissue donor screening for Mycobacterium tuberculosis—Recommended criteria and literature review

AbstractAfter two multistate outbreaks of allograft tissue‐transmitted tuberculosis (TB) due to viable bone, evidence‐based donor screening criteria were developed to decrease the risk of transmission to recipients. Exclusionary criteria, commentary, and references supporting the criteria are provided, based on literature search and expert opinion. Both exposure and reactivation risk factors were considered, either for absolute exclusion or for exclusion in combination with multiple risk factors. A criteria subset was devised for tissues containing viable cells. Risk factors for consideration included exposure (e.g., geographic birth and residence, travel, homelessness, incarceration, healthcare, and workplace) and reactivation (e.g., kidney disease, liver disease, history of transplantation, immunosuppressive medications, and age). Additional donor considerations include the possibility of sepsis and chronic illness. Donor screening criteria represent minimal criteria for exclusion and do not completely exclude all possible donor TB risks. Additional measures to reduce transmission risk, such as donor and product testing, are discussed but not included in the recommendations. Careful donor evaluation is critical to tissue safety.

Physical exercise, the immune system and infection risk: implications for prehabilitation and rehabilitation for solid organ transplantation candidates and recipients.

Solid organ transplantation recipients have an increased risk of infection, exacerbated by immunosuppressant medications that need to finely balance suppression of the immune system to prevent allograft rejection while avoiding over-suppression leading to infections and malignancy. Exercise modulates immune functions, with moderate-intensity activities particularly associated with enhanced antiviral immunity and reduced infection incidence. However, investigations of the effects of exercise and physical activity on immune function and infection risk posttransplantation are scarce. This review highlights areas where the relationship between exercise, immune function and infection risk has greatest potential for benefit for solid organ transplantation and therefore greatest need for investigation. Moderate and higher intensity exercise do not appear to cause adverse immunological effects in kidney transplantation recipients, although evidence from other organ transplantation is lacking. Evidence from healthy younger and older adults suggests that regular exercise can reduce risk of respiratory infections and latent herpesvirus reactivation and improves antibody responses to vaccination, which is of great importance for organ transplantation recipients. There is a strong need for research to investigate the role of exercise on immune function and infection risk in solid organ transplantation to improve both allograft survival and long-term health of the recipient.

Exploring Acute Pancreatitis in Kidney Transplant Recipients: A Multicentre Retrospective Cohort Analysis of Incidence, Causes, and Clinical Outcomes.

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

Multimodal Prehabilitation for Patients with Crohn's Disease Scheduled for Major Surgery: A Narrative Review.

Approximately 15-50% of patients with Crohn's disease (CD) will require surgery within ten years following the diagnosis. The management of modifiable risk factors before surgery is essential to reduce postoperative complications and to promote a better postoperative recovery. Preoperative malnutrition reduced functional capacity, sarcopenia, immunosuppressive medications, anemia, and psychological distress are frequently present in CD patients. Multimodal prehabilitation consists of nutritional, functional, medical, and psychological interventions implemented before surgery, aiming at optimizing preoperative status and improve postoperative recovery. Currently, studies evaluating the effect of multimodal prehabilitation on postoperative outcomes specifically in CD are lacking. Some studies have investigated the effect of a single prehabilitation intervention, of which nutritional optimization is the most investigated. The aim of this narrative review is to present the physiologic rationale supporting multimodal surgical prehabilitation in CD patients waiting for surgery, and to describe its main components to facilitate their adoption in the preoperative standard of care.

The Gut Microbiome and Symptom Burden After Kidney Transplantation: An Overview and Research Opportunities.

Many kidney transplant recipients continue to experience high symptom burden despite restoration of kidney function. High symptom burden is a significant driver of quality of life. In the post-transplant setting, high symptom burden has been linked to negative outcomes including medication non-adherence, allograft rejection, graft loss, and even mortality. Symbiotic bacteria (microbiota) in the human gastrointestinal tract critically interact with the immune, endocrine, and neurological systems to maintain homeostasis of the host. The gut microbiome has been proposed as an underlying mechanism mediating symptoms in several chronic medical conditions including irritable bowel syndrome, chronic fatigue syndrome, fibromyalgia, and psychoneurological disorders via the gut-brain-microbiota axis, a bidirectional signaling pathway between the enteric and central nervous system. Post-transplant exposure to antibiotics, antivirals, and immunosuppressant medications results in significant alterations in gut microbiota community composition and function, which in turn alter these commensal microorganisms' protective effects. This overview will discuss the current state of the science on the effects of the gut microbiome on symptom burden in kidney transplantation and future directions to guide this field of study.

Screening for ocular toxicities of immunotherapy in a real-world population.

e24125 Background: Nivolumab, Pembrolizumab, and Ipilimumab have revolutionized the treatment of melanoma. However, patients receiving these treatments risk immunotherapy-related adverse events (IRAEs). IRAEs can occur in any organ system, are treated with steroids or immunosuppressive medications, and may require treatment delay or discontinuation. Ocular IRAEs, which are caused by off-target reactions with ocular immune mechanisms, are often identified after significant damage to the eye. Ocular IRAEs are rare in the literature with an approximate prevalence of 3.3%. After observing intraocular inflammation (uveitis) with uveal depigmentation (pigment release) in some patients receiving immunotherapy, we hypothesized that the rate of such events in a real-world population may be higher than previously reported. We predict ophthalmic screening and early intervention may prevent severe and potentially permanent ocular IRAEs. Methods: Patients starting immunotherapy for melanoma were referred to an ocular screening clinic at the Cancer Centre of Southeastern Ontario (Queen’s University, Kingston, Canada) for baseline ocular assessments. Repeat assessments occurred every three months (single agent) or at every cycle (dual immunotherapy). Intake visits included examination by an attending ophthalmologist, including examination for uveitis and anterior chamber free pigment under high-powered field. Intraocular inflammation (IOI) was defined as the presence of endothelial deposits and/or anterior chamber cell and/or pigment that was not present at baseline. Ocular findings were monitored alongside other IRAEs during treatment. Results: 28 patients (17 male, 11 female) receiving adjuvant (46.4%) or palliative (53.6%) immunotherapy for melanoma were evaluated. 9 of these patients received dual immunotherapy (Ipilimumab/Nivolumab) and 19 received single agent immunotherapy. IOI was identified in 11 patients (39.2%), while only 4 presented with symptoms. None of the patients had overt signs of anterior segment inflammation such as erythema, conjunctival injection, and chemosis. IOI developed in 54.5% of dual immunotherapy-treated patients. Patients with ocular IRAEs were treated with topical/systemic steroids or other immunosuppressive medications. None required discontinuation of immunotherapy. The development of IOI was more common in metastatic patients whose cancer was responding to immunotherapy, and many of these patients sustained IRAEs in other organ systems. Conclusions: Our findings suggest IOI related to ocular IRAEs are quite common and develop in a third of patients receiving immunotherapy for melanoma. Ocular screening for IOI identified early, often asymptomatic toxicities that could progress to permanent visual disability. Further evaluation of dedicated ocular screening is indicated in patients receiving immunotherapy.

P160 Evaluating the process of initiating elexacaftor/tezacaftor/ivacaftor in lung transplant recipients and its effects on immunosuppression medication

P160 Evaluating the process of initiating elexacaftor/tezacaftor/ivacaftor in lung transplant recipients and its effects on immunosuppression medication

The timing of checkpoint inhibition in relation to stem cell transplantation increases the risk of inflammatory adverse events.

e14706 Background: Stem cell transplantation (SCT) and immune checkpoint inhibitors (ICIs) are both used to treat hematological malignancies. There may sometimes be an overlap in the patient’s exposure to both treatments. Theoretically, ICIs potentiate the graft-versus-tumor effect following SCT but may increase the risk of inflammatory adverse events (AEs). Conversely, immunosuppression following SCT may decrease the risk of immune-mediated AEs. We aim to explore the effect of immunotherapy on the risk and severity of inflammatory AEs following SCT. Methods: We performed a single-center, retrospective chart review including all patients with a hematological malignancy who were treated with immunotherapy and received SCT. Patients who did not receive immunosuppressive regimens after their transplant (e.g., autologous transplants) were excluded. Patients were divided into 2 groups based on the timing of ICI: pre-SCT ICI (group 1) and post-SCT ICI (group 2). We gathered clinical data including patient demographics, post-SCT immunosuppressive regimens, and pre- and post-SCT inflammatory AEs. Results: 63 patients were included. Around 82% of patients in group 1 experienced a post-transplant AE compared to 50% in group 2 ( p = 0.014). These AEs occurred earlier in group 1 patients (median 57 days in group 1 vs. 195 in group 2; p = 0.007). Roughly 80% of the inflammatory conditions involved the gastrointestinal system. Severity and complication rates did not differ between groups, but gastrointestinal inflammation in group 1 was more likely to require immunosuppressive medication (75.7% and 37.8% requiring corticosteroids and selective immunosuppressive therapy, respectively, in group 1 patients vs. 33.3% and 0% in group 2 patients; p &lt; 0.05). Conclusions: To our knowledge, our study is one of few exploring the impact of ICI timing in relation to SCT on the risk of post-SCT inflammatory AEs. Administration of immunotherapy prior to SCT may predispose patients to inflammatory AEs after SCT, which may occur earlier and last longer than if ICIs are started after SCT. Future studies are needed to further explore this phenomenon. [Table: see text]

Two-step versus three-step proctocolectomy for ulcerative colitis: a comparative study on nutritional status, immunosuppressive therapy, and long-term outcome.

Despite novel medical therapies, rates of surgery in ulcerative colitis remain relevant. While various surgical approaches for multistep proctocolectomy are available, overall evidence is low and robust recommendations are lacking for individual procedures especially in case of refractory inflammation and signs of malnutrition. All patients who received multistep proctocolectomy between 2010 and 2021 for ulcerative colitis were evaluated and divided into two groups (two-step/2-IPAA [ileal pouch-anal anastomosis] versus three-step/3-IPAA proctocolectomy). Patient characteristics as well as short- and long-outcomes were individually analyzed. Surgical techniques were explained in detail. Fifty patients were included in the study with 27 patients receiving 2-IPAA and 23 patients 3-IPAA. Rates of postoperative complications were comparable for both groups. While patients receiving 2-IPAA were more often suffering from malignancy, 3-IPAA resulted in a significant increase of hemoglobin and albumin levels as well as a reduction of immunosuppressive medication. Rates of stoma reversal trended to be reduced for 3-IPAA compared to 2-IPAA (52.2% vs. 77.8%, p = 0.06). Three-step proctocolectomy with creation of sigmoidostomy is a safe procedure and reasonable surgical approach in patients with preoperatively high dosages of immunosuppressive medication or risk factors such as persistent active inflammation and anemia.

Tinea Incognito: Challenges in Diagnosis and Management.

Tinea incognito is a dermatophyte infection with atypical features, due to the use of topical or systemic steroids or other immunosuppressive medications. Delayed diagnosis, spread of the infection to critical body surfaces, resistance to antifungal drugs, and increased costs due to prolonged hospitalization and multiple treatment regimens often complicate tinea incognito. It can affect individuals of all ages and genders, but it is more common in children. Atypical clinical appearance often necessitates differentiation from other diseases such as eczema, seborrheic dermatitis, lupus erythematosus, psoriasis, or other non-fungal skin conditions. The treatment of tinea incognito usually involves discontinuation of topical steroids or other immunosuppressive medications. Preventive measures and management of the underlying fungal infection are necessary and can be achieved with antifungal drugs. Patients should wear loose cotton clothes, use boiling water for laundry, and iron their clothing before wearing them. Additionally, they should avoid sharing bed linens, towels, clothes, and shoes. This review aims to raise awareness of tinea incognito among health practitioners, provide tips for detecting the disorder, include it in the differentials, and evaluate the available diagnostic procedures.