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Purpose Minimally invasive surgery (MIS) with integrated enhanced recovery pathways (ERPs) helps reduce length of stay and improve surgical outcomes. As these procedures have become more prevalent over time, pharmacists are in key positions to manage medications in the perioperative space to help optimize transitions of care and reduce safety events. Here we identify several clinical areas across phases of care for these procedures in which the knowledge and guidance of pharmacists, as members of the interprofessional team, are paramount. Summary Perioperative pharmacy expertise is often required for MIS procedures in the areas of acid suppression, antithrombotic management, blood glucose control, drug formulation, immunosuppressant optimization, pain mitigation, and postoperative nausea and vomiting prevention and treatment. For each MIS procedure, pharmacists should identify and consider diet and anatomical changes as well as patient- and surgery-specific risk factors. Pharmacists can then utilize their knowledge of the pharmacokinetics and pharmacodynamics of individual medications along with evidence-based medicine to recommend selection of appropriate agents. Conclusion Pharmacist contributions to perioperative medication management for MIS procedures can improve care as surgical patients navigate transitions through the perioperative setting. Pharmacists can further incorporate medication expertise through development and implementation of institutional MIS protocols within the context of ERPs. As such, any pharmacist should feel empowered to aid in the care of surgical patients. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract, and its etiology remains unclear. Presently, main drugs such as aminosalicylic acid, glucocorticoid, immunosuppressive and biological agents are employed to treat IBD. However, because of the long-term use of medication, it adversely affects other human organs. Therefore, natural bioactive compounds are applied as supplements or alternative drugs to alleviate IBD. As a kind of plant natural compounds with strong antioxidant and anti-inflammatory activities, carotenoids have exhibited potent effects in reducing intestinal inflammation. However, direct oral administration of carotenoids might cause the low specificity of inflammatory sites, which is attributed to its poor aqueous solubility and limited stability. The construction of nutrient delivery system has become an effective, efficient and dependable means. This review summarizes the delivery systems loaded with carotenoids, explores their mechanism and applications in alleviating IBD, and aims to provide corresponding theoretical references for developing novel delivery systems and their practical prospects in IBD. [ABSTRACT FROM AUTHOR]

Melanoma is the most aggressive type of skin cancer, with few therapeutic alternatives following metastasis development. In recent years, drug delivery-associated nanotechnology has shown promising targeted results with diminished adverse effects compared to conventional treatments. This study aimed to (1) examine the effects of plant-derived α-arbutin, a natural compound and (2) compare these findings with bioactively developed liposomes containing α-arbutin utilizing the B16-F10 murine melanoma cell line as a model. Liposomes were obtained through reversed-phase evaporation by applying a spray dryer to assess their stability. The following biologic assays were measured cytotoxicity/antiproliferative (MTT, Neutral Red, and dsDNA PicoGreen). In addition, the levels of melanin and purinergic enzymes were also measured. The production of reactive oxygen species (ROS) and nitric oxide (NO) was determined as a measure of oxidative state. Treatment with nano-liposome containing alpha-arbutin induced a significant 68.4% cytotoxicity, similar to the positive control, in the B16-F10 murine melanoma cell line at 72 hr. Further, arbutin and liposomes containing alpha-arbutin increased levels of ROS and nitrite formation at 72 hr at the highest concentration (100 and 300 µg/ml) of treatments. Arbutin and liposomes containing alpha-arbutin reduced melanin levels at all tested concentrations. In addition, arbutin and alpha-arbutin containing liposomes lowered nucleotides (AMP, ADP, and ATP) and nucleoside (adenosine) levels in melanoma cells. Evidence suggests that α-arbutin containing liposome can be considered as an alternative immunosuppressive agent stimulated in melanoma treatment. [ABSTRACT FROM AUTHOR]

Delayed pressure urticaria (DPU) is a subset of chronic inducible urticaria. It is characterized by the formation of wheals anytime between 30 minutes and 24 hours after stimulus exposure of localized pressure application. In this case report, we discuss a military flight crew member with no significant past medical history who developed DPU following rapid decompression in an altitude chamber. The chamber training included an uneventful ascent to 45,000 feet, higher than he had been previously, and a rapid decompression. About 16 hours later, he developed pruritic swelling of his hands and feet, along with diffuse deep nodular swelling, erythematous plaques, and erythematous nodules. His DPU was refractory to monotherapy treatment with antihistamines, and he continued to develop lesions in weight-bearing areas. Control of symptoms was achieved through combination treatment of a second-generation antihistamine, a leukotriene receptor antagonist, and an immunosuppressant (cyclosporine). His waiver to return to flight status was denied while on cyclosporine. He was transitioned to a monoclonal antibody that binds free immunoglobin E (omalizumab) with resolution of symptoms and was cleared to return to active duty. [ABSTRACT FROM AUTHOR]

Objectives: Transplantation is a form of treatment that requires long-term pharmacotherapy. After transplantation, patients may have difficulty adapting to medication use for various reasons, and this may result in rejection. The aim of this study is to determine participants' medication compliance and the factors affecting it. Methods: The research was conducted with a sequential explanatory mixed method. In the study, quantitative data were collected using the Turkish Immunosuppressive Medication Adherence Scale, and qualitative data were collected using the In-Depth Individual Interview Guide. Quantitative data were analyzed using statistical methods, and qualitative data were examined according to Braun and Clarke's thematic analysis framework. Results: In this study, 62.3% of the participants were male, 37.0% were 50 years old and over, 71.3% lived with their spouse, 54.0% had primary and secondary school education, and 42.0% could not work due to their current health condition. From a clinical perspective, it was determined that 78% of the transplants were kidney transplants, and 41.3% were more than 4 years after transplantation. 74.3% of the transplants were from living donors. The mean score of the immunosuppressive medication compliance scale was determined to be 40.91±4.09. In the qualitative data analysis of the study, factors affecting medication adherence were examined and the themes of "individual factors", "complexity of the regimen" and "social support resources" were obtained. The sub-themes of the individual factors theme are reluctance, hopelessness and addiction; Sub-themes of the complexity of the regimen theme are drug side effects and polypharmacy; The sub-themes of the social support resources theme are loneliness and family pressure. Conclusions: The factors influencing medication adherence among organ transplant recipients have been investigated, revealing that adherence levels vary significantly depending on various factors. These findings underscore the importance of tailored care strategies and individualized support approaches. [ABSTRACT FROM AUTHOR]

Background: There are both objective and subjective measures of success following ventral hernia repair (VHR). Using the Abdominal Core Health Quality Collaborative (ACHQC) database, we sought to determine if there is an association between 30-day wound events (objective) and changes in the hernia-related quality-of-life (HerQLes) scores, (subjective). We hypothesized that patients who do not experience a 30-day wound event have a greater improvement in their HerQLes score over the short-term. Methods: All adult patients who underwent VHR with 30-day follow-up data available between 2013 and 2022 were identified within the ACHQC database. The 30-day wound events included surgical site infection (SSI), surgical site occurrence (SSO), and SSO requiring procedural intervention (SSOPI). The association between 30-day wound events and changes in HerQLes scores was measured using propensity matched score analysis. Further, regression analysis was used to determine if an improvement in HerQLes score at 30-days postoperatively was associated with the likelihood of experiencing a 30-day wound event. Results: Following a 3:1 matched analysis, 17,796 patients were available for analysis; 4449 (25%) patients experienced a 30-day wound event. The most common SSI was a superficial SSI and the most common SSO was a seroma. A 10-point improvement in the HerQLes score was statistically associated with a 3% decrease in SSI and a 4% decrease in the odds of experiencing an SSO. While not statistically significant, a 10-point improvement in the HerQLes score was associated with a 2.4% decrease in the odds of experiencing an SSOPI. Conclusions: Subjective and objective measures of success following VHR seem to be correlated with one another over the short-term. Additional studies are needed to determine if this correlation exists with other subjective and objective measures of success and to determine if these correlations persist over the long-term. If present, these associations may help to guide patient counseling as experiencing a postoperative wound event following ventral hernia repair may not be detrimental to their quality-of-life over the long-term. [ABSTRACT FROM AUTHOR]

Key points: Novel topical therapeutics require extensive pre‐clinical testing to assess efficacy and safety.Antibiofilm or immunosuppressant agents can utilize ex vivo models to measure ciliotoxicity.Agents that are found to be effective and non‐toxic ex vivo warrant further investigation in vivo. [ABSTRACT FROM AUTHOR]

Kidney transplantation in children with end‐stage kidney disease significantly enhances survival and quality of life but poses unique challenges related to chronic immunosuppressive therapy. In fact, despite being essential for preventing organ rejection, immunosuppressive therapy can have significant side effects specific to pediatric patients, such as adverse impacts on physiological growth, puberty, and fertility. The resulting short stature and delayed or incomplete pubertal development can profoundly affect young patients' psychological and social well‐being, impacting self‐esteem and overall quality of life, and may significantly hamper compliance and therapeutic adherence. Most studies on immunosuppression in pediatric kidney transplant recipients focus on general side effects and outcomes like long‐term graft survival or acute complications. On the other side, there is limited evidence in the current literature on the specific issues of growth, puberty, and fertility in this patient population. In this pragmatic review, we aimed to summarize the most relevant information available on these critical aspects of post‐transplant management in pediatric patients, also providing some practical indications on management strategies for minimizing these often neglected but still important complications. [ABSTRACT FROM AUTHOR]

Acne fulminans (AF) is a severe form of inflammatory acne commonly associated with adolescents. It is characterized by an abrupt onset of painful nodules and plaques and can progress to suppurative, ulcerative, and hemorrhagic lesions. AF can be associated with systemic symptoms such as fever, arthralgia, and bone pain. The etiology of AF is unknown but it has been linked to the use of certain medications and has been rarely found in autoinflammatory syndromes. In previous years, there have been reports of <200 cases in the literature; however, AF may be more common in clinical practice than reported. The most common presentation of AF is seen in adolescents starting isotretinoin therapy. Diagnosis of AF is determined based on its clinical findings. The main purpose of this article is to provide clinicians with a practical approach to treating AF. Current evidence for its treatment is limited to case reports and case series. The mainstay treatment of AF is a combination of prednisone and isotretinoin. It is important to taper or discontinue any exacerbating or precipitating medications such as isotretinoin, antibiotics, or androgens when AF is identified. Along with treatment of AF, it is important to treat associated scarring. Early identification and treatment of AF in adolescents is crucial to minimize both acute symptoms and long-term scarring, and further research is needed to determine optimal management. [ABSTRACT FROM AUTHOR]

Twelve compounds, comprising of four new ones, 6β,7α-limondiol (1) and ethyl 19-hydroxyisoobacunoate diosphenol (2), N-benzoyl 3-prenyltyramine (9) and 9-O-methyl integrifoliodiol (12), were isolated from the twigs with leaves of Tetradium trichotomum. The structures were elucidated by analysis of MS, NMR, and single-crystal X-ray diffraction. Compounds 1, 6, 8, 9 and 12 exhibited immunosuppressive activities in vitro against the proliferation of ConA-induced T lymphocytes and LPS-induced B cells. [ABSTRACT FROM AUTHOR]

Objective: To identify the risk factors for relapse of idiopathic inflammatory myopathies (IIMs). Methods: Patients who were newly diagnosed with IIMs and underwent muscle biopsy between 2000 and 2017 at Asan Medical Center were retrospectively reviewed. The relapse of IIMs was defined as the recurrence of muscle or cutaneous manifestations with a ≥50% increase in glucocorticoid dosage after reaching the low-dose glucocorticoid phase with clinically significant improvement. The factors associated with the relapse of IIMs were investigated by Cox proportional hazards analysis. Results: Of 105 patients with IIMs, relapse was observed in 65 patients (62%). The titer of antinuclear antibody (ANA) was higher in the relapse group than in the non-relapse group (P = 0.033). Multivariable analysis showed that the relapse of IIMs was significantly associated with histopathologic features consistent with IIMs (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.01–2.83, P = 0.045) and the use of immunosuppressants before relapse (HR, 0.50; 95% CI, 0.29–0.86, P = 0.013). Doubling of ANA titer was also associated with relapse, albeit without statistical significance (HR, 1.13; 95% CI, 1.00–1.27, P = 0.052). Conclusion: In patients with IIMs, the use of immunosuppressants had a significant negative association with relapse. Administering immunosuppressants from the early period during the initial glucocorticoid tapering phase may be useful in reducing the risk of relapse in patients with IIMs. Key Points • Since idiopathic inflammatory myopathies (IIMs) have a low prevalence, it is poorly understood which factors are associated with the relapse of IIMs. • In this study, about two-thirds of 105 patients with IIMs experienced a relapse of IIMs. • The risk of relapse in patients with IIMs was negatively associated with the use of immunosuppressants during glucocorticoid tapering and low-dose glucocorticoid phase. • Even in less severe cases, the use of immunosuppressants might be a good option for the management of IIMs. [ABSTRACT FROM AUTHOR]

Anti‐phospholipid syndrome (APS) nephropathy is an autoimmune disease that is sometimes accompanied by systemic lupus erythematosus (SLE). Here, we report the use of rituximab to treat a case of APS nephropathy in a SLE patient with recurrent vascular thrombosis. A 52‐year‐old woman, who had been diagnosed with SLE 11 years earlier, was referred to a nephrology clinic for evaluation of azotaemia and proteinuria. She had experienced spontaneous abortion at 35 years of age. The patient had been diagnosed with right popliteal thrombosis at 39 years of age, and with left pulmonary artery thrombosis and SLE at 41 years of age. Before admission, she was undergoing anticoagulant and immunosuppressive therapies, with follow‐up in the rheumatology clinic. At her last outpatient clinic visit before admission, she exhibited mild bilateral lower‐limb pitting oedema, impaired renal function and proteinuria. Renal biopsy revealed arteriolar wall thickening, with thrombi in the capillary lumina and marked inflammatory cell infiltration in the interstitium. The patient was treated with warfarin and high‐dose corticosteroids. Intravenous rituximab (500 mg) was also administered twice at a 4‐week interval. Her renal function did not worsen any further, and her proteinuria decreased. Here we report the successful use of rituximab to treat APS nephropathy in a patient with SLE, who had progressive renal insufficiency. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the efficacy and safety of treatment escalation by initiating therapeutic agents in serologically active clinically quiescent (SACQ) patients with systemic lupus erythematosus (SLE). We retrospectively evaluated SACQ patients with SLE for ≥ 180 days, with the introduction of a therapeutic agent for SLE defined as exposure. The efficacy endpoints included the time to flare and time to remission, whereas the safety endpoint was the incidence of adverse events. The efficacy endpoints were assessed via Cox proportional hazards model with time-dependent covariates, which included exposure, serological activity, and prednisolone dose. Among 109 SACQ patients, 24 were initiated on the following therapeutic agents for SLE: hydroxychloroquine (10 patients), belimumab (6 patients), and immunosuppressive agents (8 patients). A total of 37 patients experienced a flare (8 and 29 patients during exposure and nonexposure periods, respectively). The time to flare was comparable between the exposure and control groups. Among 68 patients who were not in remission at the start of observation, 27 patients achieved remission (5 and 22 patients during exposure and nonexposure periods, respectively). Although both groups had a similar time to remission, the exposure group treated with belimumab had a significantly higher rate of remission than the control group. The adverse events were more frequent during the exposure period than during the nonexposure period. Thus, this study did not reveal a clear influence of treatment escalation on flare prevention and remission achievement. [ABSTRACT FROM AUTHOR]

Background: Recurrence of focal segmental glomerulosclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) after kidney transplant leads to significant morbidity and potentially earlier allograft loss. To date however, reported rates, risk factors and treatment outcomes have varied widely. Methods: We applied computational phenotypes to a multicenter aggregation of electronic health records data from 7 large pediatric health systems in the USA, to identify recurrence rates, risk factors, and treatment outcomes. We refined the data collection by chart review. Results: From > 7 million patients, we compared children with primary FSGS/SRNS who received a kidney transplant between 2009 and 2020 and who either developed recurrence (n = 67/165; 40.6%) or did not (n = 98/165). Serum albumin level at time of transplant was significantly lower and recipient HLA DR7 presence was significantly higher in the recurrence group. By 36 months post-transplant, complete remission occurred in 58.2% and partial remission in 17.9%. Through 6 years post-transplant, no remission after recurrence was associated with an increased risk of allograft loss over time (p < 0.0001), but any remission showed similar allograft survival and function decline to those with no recurrence. Since treatments were used in non-random fashion, using spline curves and multivariable non-linear analyses, complete + partial remission chance was significantly higher with greater plasmapheresis sessions, CTLA4-Ig doses or LDL-apheresis sessions. Only treatment with anti-CD20, CTLA4-Ig agents, or LDL-apheresis sessions were associated with complete remission. Excluding 25 patients with mutations did not significantly change our results. Conclusions: Our contemporary high-risk cohort had higher favorable response rates than most prior reports, from combinations of agents. [ABSTRACT FROM AUTHOR]

Background: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. Methods: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. Results: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients. Conclusions: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS. [ABSTRACT FROM AUTHOR]

Masticatory myositis (MM) is an inflammatory myopathy reported in dogs and is characterized by inflammation of the masticatory muscles (temporalis, masseter, and pterygoid muscles). Immunosuppressive therapy is the current recommended treatment for MM and may involve glucocorticoids, cyclosporine, azathioprine, mycophenolate mofetil, leflunomide, or a combination of these treatments that are slowly tapered to the lowest effective dose. However, side effects from multimodal medical therapy and complications associated with MM relapses have been reported. The purpose of this case series was to report oclacitinib as a treatment alternative to traditional medical management of MM. The intent of this alternative is to manage side effects from glucocorticoid use. Oclacitinib (1mg/kg per os q12h) was used solely for treatment of MM in three dogs. The dogs were followed up to >6 months after oclacitinib administration. An increase in oral range of motion, as determined by gape angle, was noted in all three dogs. However, a corresponding drop in antibody titers (2M fiber) did not occur. All dogs showed improvement in overall clinical management of MM, side effects from glucocorticoids, and clinical signs related to chronic prednisone use. Larger controlled trials with consistent measurements (interincisal distance, gape angle) and 2M fiber antibody titers are indicated to further assess validation of oclacitinib treatment of MM. The clinical outcome of all dogs was considered successful. [ABSTRACT FROM AUTHOR]

Monitoring the status of grafts and the occurrence of postoperative complications, such as rejection, is crucial for ensuring the success and long-term survival of organ transplants. Traditional histopathological examination, though effective, is an invasive procedure and poses risks of complications, making frequent use impractical. In recent years, graft-derived cell-free DNA (gd-cfDNA) has emerged as a promising non-invasive biomarker. It not only provides early warnings of rejection and other types of graft injury but also offers important information about the effectiveness of immunosuppressive therapy and prognosis. gd-cfDNA shows potential in the monitoring of organ transplants. The early, real-time information on graft injury provided by gd-cfDNA facilitates timely individualized treatment and improves patient outcomes. However, the progress of research on gd-cfDNA varies across different organs. Therefore, this article will comprehensively review the application and findings of gd-cfDNA in monitoring various solid organs, discussing the advantages, limitations, and some future research directions to aid in its clinical application. [ABSTRACT FROM AUTHOR]

Background Objectives Materials and methods Results Conclusions Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce.To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health.Data from the FDA adverse event reporting system (FAERS) were analyzed (2010–2022). Disproportionality analyses were used to identify signals of each drug‐adverse event pair associated with paternal drug exposure in a different hierarchical manner.Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam‐small for dates baby and finasteride‐cryptorchidism were particularly significant (reporting odds ratio, ROR > 800, N > 10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept‐skeletal dysplasia, and tacrolimus‐talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti‐tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin.This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases—abortion, diazepam—small for date baby, finasteride—cryptorchidism, etoposide and cisplatin‐13 trisomy. [ABSTRACT FROM AUTHOR]

Long-term tolerance in the absence of immunosuppressive drugs is a major goal in the transplantation field, not yet attained. Recent research on the role of commensal microbiota in the control of immunity has opened new avenues for the search of novel clinical interventions. Indeed, products of intestinal metabolism generated by both host cells and the microbiota have been identified as modulators of the immune response. Among these, tryptophan (Trp) and its derivatives are being investigated to understand their impact on alloimmunity and their potential usefulness as therapeutic targets to improve allograft survival. Here, we reviewed the latest findings on the contribution of Trp metabolic pathways to transplant outcomes. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. Methods: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. Results: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24–3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17–3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37–4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07–2.17; p = 0.026), diabetes (1.44, 95%CI 1.14–1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06–1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04–1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25–0.78; p < 0.001). Conclusion: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionTo evaluate differences in the incidence of ocular complications among pediatric and young adult patients with non-infectious uveitis receiving immunosuppressive therapy (IMT), according to the time from uveitis onset to IMT initiation in Japan.Patients aged < 20 years exhibiting uveitis treated with IMT (e.g. methotrexate, cyclosporine, infliximab, or adalimumab) were categorized into three groups according to the time from uveitis onset to IMT initiation: ≤6 months, early IMT group; 7 months to 2 years, intermediate IMT group; and ≥ 2 years, late IMT group. The percentage of ocular complications was compared among these groups. Laser flare values were recorded to evaluate disruption of the blood-aqueous barrier (BAB).Forty-three patients (84 eyes) who received IMT during the follow-up period were included. Among them, 28 patients (65.1%) experienced ≥ 1 ocular complication, with percentage of 56.0% in the early IMT group, 77.8% in the intermediate group, and 77.8% in the late group. Common complications were cataract (27.4%), posterior synechiae (17.9%), and macular edema (10.7%). The early IMT group did not require surgical intervention. The late IMT group experienced a high percentage of ocular complications despite IMT initiation. The mean laser flare value during follow-up was consistently higher in the late group (113.2 pc/ms) than in the early group (14.4 pc/ms) and intermediate group (28.7 pc/ms).In pediatric and young adult patients with chronic non-infectious uveitis, early IMT initiation may prevent permanent breakdown of the BAB, reduce the incidence of ocular complications, and decrease the need for surgical intervention. [ABSTRACT FROM AUTHOR]

Practical Application Systemic lupus erythematosus (SLE) is an autoimmune disease that affects various organs in the body. In SLE, inflammatory cytokines play a crucial role in initiating and sustaining the inflammatory process. Synbiotics may help modulate these inflammatory cytokines. This randomized, double‐blind, placebo‐controlled clinical trial aimed to assess the impact of synbiotics intervention on interleukin‐17A (IL‐17A) levels, disease activity, and inflammatory factors in patients with SLE. Fifty SLE patients were randomly assigned to receive either standard therapy plus synbiotics (consisting of Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus rhamnosus, Lactobacillus salivarius, Lactobacillus reuteri, Bifidobacterium lactis, Bifidobacterium longum, Bifidobacterium bifidum, and the prebiotic fructooligosaccharides) or standard therapy alone for 2 months. The results demonstrated a significant reduction in both protein and mRNA levels of IL‐17A, as well as in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, within the synbiotics group after the intervention compared to baseline. In contrast, the placebo group did not experience significant changes in IL‐17A levels or disease activity. Synbiotic supplementation shows potential as an adjunctive therapeutic approach for SLE management; however, further research is needed to elucidate its underlying mechanisms.This study explores the use of synbiotics as a supplementary treatment for systemic lupus erythematosus, which is typically managed with immunosuppressive therapies. [ABSTRACT FROM AUTHOR]

The article discusses the successful treatment of a patient with refractory immune-mediated thrombotic thrombocytopenic purpura (iTTP) using daratumumab after multiple failed treatments, including splenectomy. Daratumumab, a humanized anti-CD38 antibody, has shown promise in treating refractory iTTP patients by rapidly increasing ADAMTS13 activity. The treatment led to a complete immunological response in most patients, with minimal adverse effects reported. The article highlights the potential of daratumumab as a promising option for multirefractory iTTP patients, although long-term efficacy and safety require further investigation. [Extracted from the article]

Background: Immunosuppressive therapy plays a crucial role in treating membranous nephropathy, with previous studies highlighting its benefits for patients with primary membranous nephropathy (PMN). Guidelines suggest that the management of membranous nephropathy should be tailored to individual risk levels. However, there is a lack of real-world studies examining the effects of immunosuppressive therapy on renal outcomes in PMN patients. This study aimed to investigate the relationship between immunosuppressive therapy and renal prognosis in PMN patients. Methods: This was a real-world retrospective study including patients diagnosed with PMN in Shenzhen Second People's Hospital and Hechi People's Hospital. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were used. Results: After propensity score-matching, 464 PMN patients were included and they were assigned to conservative and immunosuppressive group in a 1:1 ratio. Immunosuppressive therapy was the protective factor of renal composite outcome (HR = 0.65, p < 0.01). Separately, the effect was significant in moderate- and high-risk but not in low-risk patients. Key influencing factors including age, blood pressure, albumin and total cholesterol levels, with slight differences among patients at different risk. Conclusions: This study demonstrates the efficacy of immunosuppressive therapy in non-low-risk PMN patients. The key factors affecting renal prognosis in patients with different risk levels are emphasized to help provide individualized treatment. [ABSTRACT FROM AUTHOR]

Background: The T cell-mediated delayed-type hypersensitivity (DTH) response is critical for elucidating cellular immune mechanisms, especially the role of memory T cells upon antigen re-exposure. This study aimed to investigate the specific effects of the immunosuppressive drugs Cyclophosphamide (CY) and Dexamethasone (DEX) on intestinal immunity and microbiota in a DTH mouse model, contributing to a more nuanced understanding of their immunomodulatory mechanisms. Methods: Female BALB/c mice were sensitized to 2,4-dinitrofluorobenzene (DNFB) and randomly allocated into control, CY, and DEX groups. The impact of CY and DEX on immune function was assessed through measurement of thymus and spleen indices, lymphocyte proliferation in mesenteric lymph nodes (MLNs) using MTT assay, and flow cytometric analysis of T cell subsets and TCR expression. Intestinal secretory IgA (sIgA) was quantified by ELISA, and gut microbiota diversity was evaluated using 16S rRNA gene sequencing. Results: CY and DEX significantly reduced the immune function in DNFB-induced sensitized mice, as indicated by decreased thymus and spleen indices, MLN enlargement, intestinal sIgA content, and ear swelling degree. Flow cytometry revealed that CY increased the proportion of total CD3+ T cells but reduced CD3+CD69+ activated T cells and CD3+TCRγ/δ+ T cells, while DEX increased CD3+CD4+ helper T cells. Both drugs induced distinct changes in gut microbiota diversity and structure, with CY enhancing α diversity and DEX reducing it. Conclusions: The study demonstrates that CY and DEX have distinct regulatory effects on the immune organ index, distribution of T cell subsets, and diversity and structure of gut microbiota on DTH-induced immune responses mice, suggesting their differential influence on intestinal mucosal immunity. These findings have implications for the development of targeted immunotherapies and understanding the interplay between immunosuppressive drugs and gut microbiota. [ABSTRACT FROM AUTHOR]

Infection of native tissues or implanted devices is common, but clinical diagnosis is frequently difficult and currently available noninvasive tests perform poorly. Immunocompromised individuals (for example transplant recipients, or those with cancer) are at increased risk. No imaging test in clinical use can specifically identify infection, or accurately differentiate bacterial from fungal infections. Commonly used [18F]fluorodeoxyglucose (18FDG) positron emission computed tomography (PET/CT) is sensitive for infection, but limited by poor specificity because increased glucose uptake may also indicate inflammation or malignancy. Furthermore, this tracer provides no indication of the type of infective agent (bacterial, fungal, or parasitic). Imaging tools that directly and specifically target microbial pathogens are highly desirable to improve noninvasive infection diagnosis and localization. A growing field of research is exploring the utility of radiometals and their chelators (siderophores), which are small molecules that bind radiometals and form a stable complex allowing sequestration by microbes. This radiometal-chelator complex can be directed to a specific microbial target in vivo, facilitating anatomical localization by PET or single photon emission computed tomography. Additionally, bifunctional chelators can further conjugate therapeutic molecules (e.g., peptides, antibiotics, antibodies) while still bound to desired radiometals, combining specific imaging with highly targeted antimicrobial therapy. These novel therapeutics may prove a useful complement to the armamentarium in the global fight against antimicrobial resistance. This review will highlight current state of infection imaging diagnostics and their limitations, strategies to develop infection-specific diagnostics, recent advances in radiometal-based chelators for microbial infection imaging, challenges, and future directions to improve targeted diagnostics and/or therapeutics. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic graft vs. host disease (cGVHD) is a major complication that appears after allogeneic hematopoietic cell transplantation. As result, this has a significant and detrimental impact on both the quality of life and survival of patients after transplantation. In recent years, three novel therapies have been approved by the FDA for the management of cGVHD. To date, previous studies have not analyzed the effect of these novel drugs on other health-associated conditions such as metabolic syndrome, bone health, return to employment, mental health, and other para-medical outcomes. In this study, during three different time periods, we aimed to assess and highlight the association between novel advanced treatments for cGVHD and their impact on the quality of life of patients after allogeneic transplantation. Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we retrospectively analyzed all patients > 18 years with cGVHD after their first hematopoietic cell transplantation (HCT) between 2012 and 2020 (n = 91), divided into three treatment periods: 2012–2014, 2015–2017, and 2018–2020 (groups 1, 2, and 3, respectively). Results—mean cumulative steroid dose and dose/total cGVHD-treatment days was lower in groups 2–3 compared to 1 (p = 0.008 and p = 0.042, respectively). The median IST-free survival was 79 (95%CI54–94) months, with more patients in group 3 (47% (95%CI 25–54%) discontinuing IST at 3 years, p = 0.1). Groups 2–3 compared to 1 had better glycemic control (p < 0.01), higher bone density (p = 0.06), and fewer cardiovascular events. The number of admissions/patient dropped from 0.7/year in group 1 to 0.24/year and 0.36/year in groups 2–3, respectively (p = 0.36). Employment reintegration was higher in groups 2–3 compared with 1 (p = 0.05) and so was earlier return to work (p = 0.01). There were no differences in survival outcomes. Conclusions—the incorporation of novel agents appears to be associated with reduced overall steroid burden, improved cGVHD control, and fewer long-term side effects. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed HBV screening on all Romanian adults hospitalized in four COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment, or baseline immunosuppressive conditions, and we conducted a virological follow-up on these patients at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed for 13 patients with positive hepatitis B surface antigen (HBsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with a de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) for all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish appropriate and cost-effective management for these patients. [ABSTRACT FROM AUTHOR]

Tacrolimus (TAC) is a commonly used immunosuppressive drug in solid organ transplantation. Pharmacogenetics has been demonstrated before to be decisive in TAC pharmacotherapy. The CYP3A5*3 variant has been reported to be the main determinant of TAC dose requirements; however, other polymorphisms have also proven to be influential, especially in CYP3A5 non-expressor patients. The aim of this study is to evaluate the influence of genetic polymorphisms in TAC therapy in a cohort of Spanish transplant recipients. Genetic analysis including ten polymorphic variants was performed, and demographic and clinical data and pharmacotherapy of 26 patients were analyzed. No significant differences were found in weight-adjusted dose between CYP3A5 expressors and non-expressors (0.047 mg/kg vs. 0.044 mg/kg), while they were found for carriers of the CYP3A4*1B allele (0.101 mg/kg; p < 0.05). The results showed that patients with at least one CYP3A4*1B allele had a higher TAC dose and lower blood concentration. Dose-adjusted TAC blood levels were also lower in CYP3A4*1B carriers compared to non-carriers (0.72 ng/mL/mg vs. 2.88 ng/mL/mg). These results support the independence of CYP3A5*3 and CYP3A4*1B variants as determinants of dose requirements despite the linkage disequilibrium present between the two. The variability in genotype frequency between ethnicities may be responsible for the discrepancy found between studies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) patients face different health challenges when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population, due to both their immunocompromised state and the immunosuppressive therapies they receive. This systematic literature review, which follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) paradigm, explores the interactions between RA and SARS-CoV-2 infection, focusing on immunologic issues, disease management, vaccination, and adverse outcomes. In order to obtain the most relevant information, we systematically reviewed the specific literature from 1 January 2021 to 31 December 2023, based on the PRISMA method, by which we eventually selected 35 eligible articles, to which we added other ISI-indexed studies to enrich our results further. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Firstly, the data collected revealed the impact of the pandemic on RA diagnoses and the fear of face-to-face medical consultations that delayed adequate treatment. Secondly, cardiovascular and metabolic comorbidities increase the risk of prolonged COVID-19 symptoms, hospitalization, and severe COVID-19 outcomes for RA patients. With respect to immunosuppressive treatment used to control RA, it was observed that glucocorticoids (especially high-dose usage) and Rituximab (RTX) predispose the patients to poor SARS-CoV-2 outcomes, as opposed to Baricitinib and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) inhibitors. COVID-19 vaccination has proven effective and generally safe for RA patients in some studies, although therapies with Methotrexate (MTX), Abatacept (ABA), and RTX have been associated with impaired vaccine immune response. This systematic literature review brings updated and thorough information with respect to the immunological, clinical, and management of a complex immune-mediated inflammatory disease (IMID) like RA in the setting of COVID-19 and underlines the challenges faced by this group of patients. The lessons learned can be extended beyond the pandemic in shaping a more informed and compassionate healthcare system and offering long-term medical care for patients with RA. [ABSTRACT FROM AUTHOR]

Urothelial carcinoma (UC), as a common malignant tumor of the urinary system, has an increasing inumber of patients. Some patients have developed into inoperable locally advanced or distant metastatic UC (la/mUC) at the initial treatment. At present, the standard treatment scheme is platinum-based chemotherapy, but the adverse reactions and therapeutic effects are not ideal. In recent years, antibody-drug conjugate combined with immune checkpoint inhibitors has gradually become a new focus of cancer precision medicine research, bringing new treatment options for these patients. Currently, there are many clinical trials in this field, and the purpose of this article was to provide a comprehensive review of the recent research progress. [ABSTRACT FROM AUTHOR]

Background Objective Design Participants Measurements Results Conclusion One of the most common problems encountered in transplant patients is nonadherence with immunosuppressive drugs, one of the most important reasons for graft rejection.The study aimed to assess the impact of text message reminders on medication adherence among kidney transplant recipients.A randomized controlled trial.The study was conducted from January to October 2021. This study included a total of 100 patients receiving a kidney transplant, 50 in the intervention group and 50 in the control group.Patients in the intervention group were sent text message reminders four times a day during the 6th–9th months after transplantation. Control patients received no such intervention. Tacrolimus concentrations in the bloodstream were monitored for all participants through measurements taken at Months 7, 8 and 9. Data collection tools included Sociodemographic Form and Immunosuppressive Medication Adherence Scale.Patients were homogeneously distributed among the groups. Sending daily text message reminders to transplant recipients caused an independent positive effect on medication adherence scale scores at the end of the study. Mean pretest medication adherence score of all patients was 45.18 ± 4.22 and posttest score was 47.4 ± 3.6. The intervention group exhibited a significantly higher mean posttest adherence score compared to controls, with values of 48.68 ± 2.58 and 45.62 ± 4.42, respectively (p < 0.001). Findings demonstrated a substantial improvement in the final medication adherence scores of transplant patients when they received daily Short Message Service reminders, acting as an independent factor (β = 0.356, p < 0.001).Sending text message reminders to kidney transplant recipients is a statistically and clinically effective intervention to improve immunosuppressive medication adherence. [ABSTRACT FROM AUTHOR]

Xenotransplantation of porcine hearts has become a promising alternative to human allotransplantation, where organ demand still greatly surpasses organ availability. Before entering the clinic, however, feasibility of cardiac xenotransplantation needs to be proven, ideally in the life supporting orthotopic pig-to-nonhuman primate xenotransplantation model. In this review, we shortly outline the last three decades of research and then discuss in detail its most recent advances. These include the genetic modifications of donor pigs to overcome hyperacute rejection and coagulation dysregulation, new organ preservation methods to prevent perioperative xenograft dysfunction, experimental immunosuppressive and immunomodulatory therapies to inhibit the adaptive immune system and systemic inflammation in the recipient, growth control concepts to avoid detrimental overgrowth of the porcine hearts in nonhuman primates, and lastly, the avoidance of porcine cytomegalovirus infections in donor pigs. With these strategies, consistent survival of 6–9 months was achieved in the orthotopic xenotransplantation model, thereby fulfilling the prerequisites for the initiation of a clinical trial. [ABSTRACT FROM AUTHOR]

AbstractFDA approved agents for the treatment of chronic GVHD including ruxolitinib and belumosudil are effective steroid-sparing agents, with overall response rates (ORR) of 76% and 65% respectively. Ruxolitinib and belumosudil are well tolerated with different primary targets. Little data is available on the use of combination ruxolitinib and belumosudil. This is a single center, retrospective analysis of 20 treatment-refractory patients with chronic GVHD treated with combination ruxolitinib and belumosudil. The ORR including complete response (CR) and partial response (PR) at any time was 55% (11/20). Among responding patients, other immunosuppressive agents were tapered or discontinued in all patients. None of the patients developed EBV or CMV reactivation requiring treatment. 4 patients (20%) developed pneumonia and 2 patients (10%) developed viral URI. Cytopenias were not exacerbated. No patients had graft failure or relapsed disease. The combination is tolerable, delays the need for alternative therapies, and facilitates tapering of corticosteroids. [ABSTRACT FROM AUTHOR]

Background: Cytomegalovirus (CMV) chronic retinal necrosis (CRN) is a rare viral retinal infection that occurs in mildly immunocompromised people. It shares some features with both acute retinal necrosis and CMV retinitis. It is typically treated with combination intravitreal and systemic ganciclovir. We discuss the management of a case of CMV CRN with ganciclovir resistance. Case presentation: An 80-year-old female presented with one month of blurry vision in the left eye. She was being treated with abatacept, methotrexate, and prednisone for rheumatoid arthritis. Examination revealed anterior chamber and vitreous cell along with peripheral retinal whitening. Fluorescein angiogram showed diffuse retinal non-perfusion. Aqueous fluid PCR testing returned positive for CMV. The retinitis was initially controlled with oral and intravitreal ganciclovir, but then recurred and progressed despite these therapies. Ganciclovir resistance was suspected and the patient was switched to intravitreal foscarnet injections, along with oral letermovir and leflunomide, which lead to resolution of the retinitis. The patient has now continued with letermovir and leflunomide for approximately 2.5 years without reactivation of the retinitis or need for further intravitreal anti-viral injections and with adequate control of her rheumatoid arthritis. Conclusion: The incidence of CMV CRN may increase in the future as the use of non-cytotoxic immunosuppressive therapies that result in relatively mild immunosuppression also increases. Treatment with ganciclovir is effective but frequently leads to resistance, as in our case. In this situation, combination therapy with letermovir and leflunomide, particularly in the setting of rheumatoid arthritis where leflunomide can also have an anti-inflammatory effect, can be considered. [ABSTRACT FROM AUTHOR]

Background: The reactivation of tuberculosis (TB) among kidney transplant (KT) recipients in an endemic area is of general concern. However, the epidemiology of latent TB infection (LTBI) status and its dynamic change responses have not been explored. Methods: Between September 2020 and August 2021, a prospective study was conducted to investigate the status of LTBI in KT recipients who received a 9-month isoniazid universal prophylaxis. This status was measured using the interferon-gamma release assay (IGRA) with T-SPOT.TB before transplant, as well as at one month and nine months post-transplant. Results: Ninety-one KT recipients had a mean (SD) age of 45 (11) years, and 41% were female. Sixty-eight (75%) patients received a deceased donor allograft, and eighty-six (91%) patients received induction immunosuppressive therapy. The IGRA results were positive, borderline, negative, and indeterminate in 14 (15.4%), 6 (6.6%), 64 (70.3%), and 7 (7.8%) patients, respectively. Among 84 evaluable patients, 20 (23.8%) KT recipients were defined as having LTBI. Older age was significantly associated with LTBI (OR 1.06 [95% CI 1.01–1.12], p = 0.03). Among the 77 KT recipients who completed monitoring, 55 had negative IGRA results. Three (5.4%) KT recipients had conversion post-transplant. One of them developed pulmonary TB at 1 week after the transplant. Among the 13 patients with positive results, 8 (61.5%) remained positive, 1 (7.7%) had an indeterminate result at 1-month post-transplant and subsequently tested positive at 9 months post-transplant, and 4 (30.8%) experienced reversion to negative results throughout the study. Conclusions: In a high TB-endemic area, one-quarter of KT recipients were reported to have LTBI, and the dynamic change of IGRA response in KT recipients is plausible post-transplant. [ABSTRACT FROM AUTHOR]

Hypersensitivity Pneumonia is a lung disease with two forms – fibrotic and non-fibrotic – which predominantly progress with lymphocytic infiltration and granulomatous inflammation as a result of both humoral and cellular response following the exposure of susceptible individuals to any antigen. In cases with the appropriate clinical features, high-resolution lung tomography can aid the diagnosis. Coarse reticulations with irregular linear opacities/lung distortions, traction bronchiectasis and honeycombing, centrilobular nodules, ground glass densities, mosaic perfusions and air imprisonment areas can be counted among the most significant radiological features. Treatment withdrawal is the basis for corticosteroids or immunosuppressive therapies, while antifibrotic agents hold promise as new treatment options in the future. In the present study, the diagnosis, imaging and treatment characteristics of three cases with Hypersensitivity Pneumonia diagnosed using different histopathological methods are reviewed in the light of current literature. [ABSTRACT FROM AUTHOR]

Introduction: Myasthenia gravis is an autoimmune disease that is charecterized by production of acetyl cholinesterase receptor auto antibodies. This is a retrospective study done in 45 patients who were offered trans-sternal thymectomy in such patients. Objectives: Adequate pre operative preparation with immunosuppressive agents and myasthenia gravis modifying drugs, plasmapheresis before surgery helps optimize out comes. Material and methods:Retrospectively data was collected from the years 2017-2020 in 45 patients who underwent trans-sternal thymectomy for myasthenia gravis and results analysed. Results: There has been no mortality noted in this study. 13 patients needed post operative management of myasthenic crisis. There was no reduction in the dosage of pyridostigmine. However, there has been a significant reduction in the dosage of steroids and azathriopine. Conclusion: Presence of thymoma, positive AChR Antibodies, moderate to severe airway disease are significant predictors of perioperative crisis. Prior adequate optimization before surgery is of utmost importance to prevent postoperative myasthenia crisis. Thymectomy is a very safe and effective procedure. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends extracorporeal membrane oxygenation (ECMO) as a therapeutic option for the most critical cases of severe coronavirus disease 2019 (COVID-19). However, data on universally agreed-upon risk factors that contribute to ECMO weaning failure and mortality in COVID-19 patients undergoing ECMO are limited. This lack of consensus leads to significant uncertainties in developing effective management strategies for these patients. We aimed to identify the factors associated with early outcomes after ECMO support in patients with COVID-19-induced acute respiratory distress syndrome, specifically the success rate of ECMO weaning and in-hospital mortality. Methods: We reviewed 25 patients with COVID-19 who received ECMO support at a single institution between January 2020 and July 2022. This retrospective data collection and review included clinical characteristics, adjunctive treatments, complications, and early patient outcomes. Results: A total of 72% of the patients were successfully weaned off ECMO, and 68% were discharged alive. Significant associations were observed between ECMO weaning success and in-hospital survival, particularly younger age and a history of rehabilitation therapy. Furthermore, the absence of a history of immunosuppressive therapy contributed significantly to successful ECMO weaning. Conclusions: Younger age and the implementation of rehabilitation therapy are associated with improved outcomes in patients with COVID-19 receiving ECMO support. [ABSTRACT FROM AUTHOR]

Simple Summary: Idiopathic granulomatous mastitis (IGM) is a rare breast disease that can be mistaken for inflammatory breast cancer. It requires a tissue biopsy for an accurate diagnosis. Even though it is not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. It is important to distinguish IGM from other breast inflammations caused by infections. IGM is mostly found in premenopausal women, often after pregnancy or breastfeeding. Smoking and contraceptive use might be risk factors, but the evidence is unclear. The treatment options include NSAIDs, steroids, immunosuppressants, surgery, prolactin suppressants, and antibiotics; many patients relapse, making treatment challenging. This review summarizes current information, which mostly comes from case reports and small studies, and presents GRAMAREG as a registry for IGM initiated by the EUBREAST Study Group, which aims to collect detailed data on IGM to improve the knowledge base for diagnosis and treatment. Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign inflammatory breast condition often mistaken for inflammatory breast cancer and, therefore, requires a biopsy for accurate diagnosis. Although not cancerous, IGM can cause emotional distress because of severe pain and ensuing breast deformity. Differentiating IGM from other breast inflammations caused by infections is essential. IGM mostly affects premenopausal women and is potentially associated with recent pregnancies and breastfeeding. The risk factors, including smoking and contraceptive use, have inconsistent associations. Steroid responses suggest an autoimmune component, though specific markers are lacking. Methods: We performed a narrative review on potential risk factors, diagnostics, and therapy of IGM. Results: Diagnostics and clinical management of IGM are challenging. The treatment options include NSAIDs, steroids, surgery, antibiotics, immunosuppressants, prolactin suppressants, and observation, each with varying effectiveness and side effects. Conclusions: Current IGM treatment evidence is limited, based on case reports and small series. There is no consensus on the optimal management strategy for this disease. The GRAMAREG study by the EUBREAST Study Group aims to collect comprehensive data on IGM to improve diagnostic and treatment guidelines. By enrolling patients with confirmed IGM, the study seeks to develop evidence-based recommendations, enhancing patient care and understanding of this condition. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous T cell lymphomas (CTCLs) are a group of rare lymphoproliferative malignancies manifesting in the skin. Cutaneous T cell lymphomas are an incurable, disfiguring, and life-threatening disease. Emerging studies have implicated the surrounding cells of malignant T cells (tumor microenvironment) in the disease evolution. This has revealed that targeting the tumor microenvironment has therapeutic potential in cutaneous T cell lymphomas. This review provides a detailed insight into the contribution of the tumor microenvironment in cutaneous T cell lymphomas and the targeting strategies. Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin lymphomas, with mycosis fungoides and Sézary syndrome being the two common subtypes. Despite the substantial improvement in early-stage diagnosis and treatments, some patients still progress to the advanced stage with an elusive underpinning mechanism. While this unsubstantiated disease mechanism coupled with diverse clinical outcomes poses challenges in disease management, emerging evidence has implicated the tumor microenvironment in the disease process, thus revealing a promising therapeutic potential of targeting the tumor microenvironment. Notably, malignant T cells can shape their microenvironment to dampen antitumor immunity, leading to Th2-dominated responses that promote tumor progression. This is largely orchestrated by alterations in cytokines expression patterns, genetic dysregulations, inhibitory effects of immune checkpoint molecules, and immunosuppressive cells. Herein, the recent insights into the determining factors in the CTCL tumor microenvironment that support their progression have been highlighted. Also, recent advances in strategies to target the CTCL tumor micromovement with the rationale of improving treatment efficacy have been discussed. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a frequent gastrointestinal malignancy with high rates of morbidity and mortality; 85% of these tumours are proficient mismatch repair (pMMR)‐microsatellite instability‐low (MSI‐L)/microsatellite stable (MSS) CRC known as 'cold' tumours that are resistant to immunosuppressive drugs. Monotherapy with programmed death 1 (PD‐1)/programmed death ligand 1 (PD‐L1) inhibitors is ineffective for treating MSS CRC, making immunotherapy for MSS CRC a bottleneck. Recent studies have found that the multi‐pathway regimens combined with PD‐1/PD‐L1 inhibitors can enhance the efficacy of anti‐PD‐1/PD‐L1 in MSS CRC by increasing the number of CD8+ T cells, upregulating PD‐L1 expression and improving the tumour microenvironment. This paper reviews the research progress of PD‐1/PD‐L1 inhibitors in combination with cytotoxic T‐lymphocyte–associated antigen 4 (CTLA‐4) inhibitors, oncolytic virus, intestinal flora, antiangiogenic agents, chemotherapy, radiotherapy and epigenetic drugs for the treatment of pMMR‐MSI‐L/MSS CRC. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: Immunocompromised children may have increased risk for severe respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI), potentially leading to prolonged hospitalization, intensive care, and death. The open-label phase II MUSIC trial evaluated the safety and pharmacokinetics of nirsevimab, an extended half-life monoclonal antibody against RSV, in immunocompromised children aged #24 months. METHODS: Participants received a single intramuscular injection of nirsevimab (first RSV season: 50 mg if <5 kg/100 mg if ≥5 kg; second season: 200 mg). Safety, antidrug antibodies, and pharmacokinetics were evaluated to day 361. RESULTS: Participants (n = 100) had ≥1 immunocompromising conditions: primary immunodeficiency (n = 33), previous transplantation (n = 16), HIV infection (n = 8) or treatment with high-dose systemic corticosteroids (n = 29), immunosuppressive chemotherapy (n = 20), or other immunosuppressive therapies (n = 15). Six children experienced eight treatment-related adverse events (none categorized as serious). Three deaths occurred, all were unrelated to treatment. Eleven children, developed antidrug antibodies, with minimal effects on pharmacokinetics and no apparent impact on safety. Nirsevimab serum concentrations at day 151 were similar to those effective in preventing medically attended RSV LRTI in healthy infants. Fourteen children had increased nirsevimab clearance. No protocol-defined medically attended RSV LRTIs occurred through day 151. CONCLUSIONS: Among immunocompromised children aged ≤24 months, nirsevimab was well tolerated with no safety concerns and serum concentrations were supportive of efficacy. A subset of children with increased nirsevimab clearance, had conditions potentially associated with protein loss; however, the impact on efficacy is unknown. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: The complexity of pediatric patients' outpatient medication regimens is increasing, and risk for medication errors is compounded in a busy emergency department (ED). As ED length of stay (LOS) increases, timely and accurate administration of essential outpatient medications has become increasingly challenging. Our objective was to increase the frequency of ordering of essential outpatient medications for patients with ED LOS >4 hours from 56%to 80% by June 2023. METHODS: We conducted a quality improvement (QI) initiative in a pediatric ED with ~60 000 annual visits comprising a total of 91 000 annual medication orders. We defined essential outpatient medications as antiepileptic drugs, cardiovascular medications, and immunosuppressants. Our QI interventions included a combination of electronic health record interventions, a triage notification system to identify patients with essential outpatient medications, and widespread educational interventions including trainee orientation and individualized nursing education. The primary outcome measure was percentage of essential outpatient medications ordered among patients with an ED LOS >4 hours,with a secondary measure of outpatientmedication safety events. RESULTS: Baseline monthly ordering rate of selected medications for patients with an ED LOS >4 hours was 54%, with an increase to 66% over the study period. Refining our population yielded a rate of 81%. Outpatient medication safety events remained unchanged, with an average of 952 ED encounters between events. CONCLUSIONS: A multidisciplinary QI initiative led to increased essential outpatient medication ordering for patients in a pediatric ED with no change in safety events. [ABSTRACT FROM AUTHOR]

Objectives The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptoms severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. Methods This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. Results The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06–6.41, P  = 0.04). Age at diagnosis and focal central events emerged as additional response predictors. Conclusion NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: We sought to determine the impact of hydroxychloroquine (HCQ) dose on the risk of hospitalizations for systemic lupus erythematosus (SLE). Methods: We conducted a case‐crossover study within an academic health system, including patients with SLE who used HCQ and had ≥1 hospitalization for active SLE between January 2011 and December 2021. Case periods ended in hospitalization for SLE, whereas control periods did not. The exposures were the average weight‐based HCQ dose, categorized as ≤5 or >5 mg/kg/day, and non–weight‐based HCQ dose, categorized as <400 or 400 mg/day, assessed during each six‐month case or control period. Odds ratios (ORs) were calculated using conditional logistic regression and adjusted for prior disease activity, kidney function, glucocorticoid use, and other immunosuppressant use. Results: Of 2,974 patients with SLE who used HCQ (mean age 36.5 years; 92% female), 584 had ≥1 hospitalization with primary discharge diagnosis of SLE. Of these, 122 had ≥1 hospitalization for active SLE while using HCQ and had ≥1 control period with HCQ use during the study period. Lower HCQ weight‐based dose (≤5 vs >5 mg/kg/day) and non–weight‐based dose (<400 vs 400 mg/day) were each associated with increased hospitalizations for active SLE (adjusted OR 4.20, 95% confidence interval [CI] 1.45–12.19, and adjusted OR 3.39, 95% CI 1.31–8.81). Conclusion: The use of lower doses of HCQ was associated with an increased risk of hospitalizations for active SLE. Although the long‐term risk of HCQ retinopathy must be acknowledged, this must be balanced with the short‐term and cumulative risks of increased SLE activity. [ABSTRACT FROM AUTHOR]