Search Results (38)

Renal cell carcinoma (RCC) is the most common type of kidney cancer, accounting for a significant proportion of all cancer cases in Korea. This case report presents a unique instance of spontaneous dramatic tumor regression in a 42-year-old Korean male diagnosed with clear cell RCC. The patient initially presented with right lower back pain, weight loss, and a loss of appetite. Following systemic immunotherapy with nivolumab and ipilimumab, and right radical nephrectomy, the patient was diagnosed with metastatic clear cell RCC, with new metastatic lesions detected in the liver, and on the chest wall on follow-up imaging. Second-line systemic treatment with pazopanib was initiated. Shortly thereafter, the patient developed severe systemic inflammatory syndrome, resulting in a mental stupor and acute kidney failure. Intensive care, including continuous renal replacement therapy and high-dose immunosuppressants, was administered. The patient’s condition improved significantly with the intensive care regimen, leading to unintended tumor regression. These potentially fatal side effects occurred without infection, as confirmed by negative blood and urine cultures, and were attributed to the recent introduction of pazopanib. Follow-up imaging showed a significant reduction in hepatic metastatic lesions and the disappearance of chest wall nodules. This is the first reported case of RCC tumor regression following the side effects of pazopanib, underscoring the need for further studies into the immune mechanisms involved in RCC treatment and highlighting potential therapeutic strategies that leverage innate immune responses. Full article

Hepatocellular carcinoma (HCC) is a leading cause of cancer death globally, with the majority of cases detected at advanced stages when curative options are limited. Current systemic therapies, including immune checkpoint inhibitors, demonstrate limited efficacy with durable responses in only 15–20% of patients. This poor response is largely attributed to HCC’s immunosuppressive microenvironment, which blunts effective T-cell responses. By illustrating that innate immune cells can acquire memory-like characteristics through a process known as trained immunity, recent evidence has challenged the conventional belief that innate immunity is devoid of memory. This review investigates the potential of trained immunity, which is defined by the long-term functional reprogramming of innate immune cells through epigenetic, transcriptomic, and metabolic changes, to provide new therapeutic opportunities for HCC. We discuss mechanisms by which trained immunity can transform the HCC microenvironment, including enhanced inflammatory cytokine production, repolarization of tumor-associated macrophages toward anti-tumor phenotypes, increased immune cell infiltration, and improved bridging to adaptive immunity. We further evaluate emerging therapeutic strategies leveraging trained immunity principles, including BCG vaccination, β-glucan administration, cytokine-trained NK cell therapy, and innovative combination approaches. Finally, we address potential resistance mechanisms and future directions for clinical application. By integrating trained immunity into conventional immunotherapeutic regimens, we may significantly improve outcomes for HCC patients, potentially transforming advanced disease into a more manageable condition. Full article

There is still an unmet need for the treatment of high-risk hematological malignancies. To date, allogeneic stem cell transplantation remains the only chance of cure. Most patients suffering from high-risk hematological malignancies are of an older age and often present with comorbidities. Moreover, patients achieving remission often suffer from early relapse. Amongst the different treatment options, sequential conditioning has yet to prove its value against other conditioning regimens. Sequential conditioning relies on a short course of intensive chemotherapy that is quickly followed by immunosuppressive conditioning before allogeneic stem cell transplantation. Here, we will try to determine which patients can benefit from sequential conditioning. Amongst the different sequential regimens, we will also try to assess if one regimen is better than all the others. Despite the several studies conducted on sequential conditioning, very few are prospective work and head-to-head comparisons are almost inexistant. Sequential conditioning also relies on the use of prophylactic donor lymphocyte infusion post-transplantation. Hence, limiting non-relapse complications is of primary importance to the allow administration of post-transplant treatment. In the era of new targeting therapies, is there still a place for sequential conditioning? Can patients benefit from an association of new therapeutic agents and sequential conditioning? Full article

Vitiligo is a chronic autoimmune pigmentation disorder shaped by a complex interplay of genetic predispositions and environmental triggers. While conventional therapies—phototherapy, corticosteroids, and immunosuppressants—can be effective, their benefits are often partial and temporary, with recurrence common once treatment stops. As such, there is increasing interest in exploring complementary approaches that may offer a more sustainable impact. Emerging evidence suggests that macronutrient and micronutrient-level changes could be beneficial for managing progression and, in some cases, facilitating repigmentation. Antioxidant-rich foods, such as apples, green tea, Indian gooseberry, onions, and peppers, may help mitigate oxidative stress, while inflammatory foods, such as gluten and high-phenol nuts and berries, may exacerbate the condition. Certain supplements, including high-dose vitamin D, vitamin C, vitamin E, and selenium, may enhance phototherapy outcomes. Omega-3 and other unsaturated fatty acids, in addition to prebiotics and probiotics, are under active investigation for their roles in gut health and immune regulation. Notably, plant-derived compounds, i.e., Ginkgo biloba, have demonstrated promise in promoting repigmentation and managing disease progression. However, it must be emphasized that these nutritional interventions remain exploratory, and more research is needed to establish their efficacy, safety, and optimal usage before they can be recommended as part of a standard treatment regimen. Full article

Scabies is a worldwide parasitic dermatosis with a significant health burden on the young and the elderly. Statistics about the prevalence of scabies in Hong Kong are not available. This is a retrospective study of patients from a regional hospital cluster in Hong Kong with microscopy-documented Sarcoptes scabiei infestations from January 2018 to December 2022. The condition was categorised into classical scabies and crusted scabies upon clinical presentation. Demographic data, comorbid diseases, mobility and residential status, seasonal variability, secondary bacterial infection, treatment and outcomes were described. These were compared between classic and crusted scabies. In total, 604 patients were identified, representing 51.65 per 100,000 discharged patients during the study period. The median age was 84 years and 54.5% were male. The majority (506 or 83.8%) came from residential care homes for the elderly. The mean time from admission to diagnosis was 8.8 days for community-acquired infestation. There were 564 and 40 cases of classic and crusted scabies, respectively. The two groups of patients were comparable in terms of residence in elderly homes, co-existing chronic illnesses, mobility, and time from admission to diagnosis. Forty-five (7.5%) patients had positive blood cultures temporally associated with scabies. Patients with crusted scabies were at higher risk for bacteraemia (7/40 versus 38/564, p = 0.022). Permethrin and benzyl benzoate were the most popular treatment regimens, with treatment failure observed in 59/397 (14.4%) and 18/173 (10.4%), respectively. There were 172 (28.5%) mortalities within 30 days of scabies diagnosis. Thus, the burden of scabies infestation is significant in Hong Kong. Hospitalised patients diagnosed with scabies are mainly senior citizens living in residential care homes for the elderly, suggesting reservoirs of S. scabiei in the community. Of concern, bacteraemic illnesses are common and significant mortality is temporarily associated with infestation. With a rising elderly population, there is a pressing need to understand and control scabies in Hong Kong. Our study did not find that common medical illness, besides immunosuppressive therapy, predisposed patients to crusted scabies. The crusted form of scabies was associated with a higher risk of bacteraemia. The current study provides a better perspective of the disease load of scabies in Hong Kong. Full article

Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of glycemia in people with previously diagnosed diabetes. The risk of adverse event development depends on the prior therapy, the duration of the treatment, the form of the drug, and individual factors, i.e., BMI, genetics, and age. Unfortunately, SID and steroid-induced hyperglycemia (SIH) are often overlooked, because the fasting blood glucose level, which is the most commonly used diagnostic test, is insufficient for excluding both conditions. The appropriate control of post-steroid hyperglycemia remains a major challenge in everyday clinical practice. Recently, the most frequently used antidiabetic strategies have been insulin therapy with isophane insulin or multiple injections in the basal–bolus regimen. Alternatively, in patients with lower glycemia, sulphonylureas or glinides were used. Taking into account the pathogenesis of post-steroid-induced hyperglycemia, the initiation of therapy with glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors should be considered. In this article, we present a universal practical diagnostic algorithm of SID/SIH in patients requiring steroids, in both acute and chronic conditions, and we present a new pharmacotherapy algorithm taking into account the use of all currently available antidiabetic drugs. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group. Full article

Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost–benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be naïve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients. Full article

Allogeneic stem cell transplantation (Allo-SCT) implies that a donor and a recipient are not genetically identical. Allo-SCT is used to cure a variety of conditions, including hematologic malignancies using the graft versus tumor effect, nonmalignant hematologic, immune deficiencies, and, more recently, genetic disorders and inborn errors of metabolism. Given the immunosuppressive and myeloablative nature of some of the conditioning chemotherapy regimens used during the Allo-SCT, patients are often at high risk of infection, including viral infections affecting the gastrointestinal tract, following the transplant. Furthermore, other complications such as hepatic sinusoidal obstruction syndrome (SOS) or graft-versus-host disease may occur post-transplant and may require endoscopy to assist in the diagnosis. This review will provide newer insights into the importance of endoscopic techniques in the diagnosis of post-Allo-SCT complications with a focus on safety and timing. Full article

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. Full article

Hemophagocytic syndrome/macrophage activation syndrome (HPS/MAS) is a serious clinical condition that frequently leads to multiple organ failure, including acute kidney injury (AKI). Although the pathogenesis of AKI is not yet fully understood, it is believed to result from uncontrolled activation of the immune system involving macrophages and cytotoxic lymphocytes. Renal histology in HPS/MAS often presents with characteristic foamy glomerular lesions (glomerular lipidosis) with massive macrophage infiltration, known as histiocytic glomerulopathy. In this review, we introduce the recently proposed concept of renal-limited HPS/MAS as a novel etiology of histiocytic glomerular lipidosis. Patients with renal-limited HPS/MAS often develop AKI but do not fulfill the diagnostic criteria for HPS/MAS because their systemic manifestations are less severe. Therefore, the diagnosis largely depends on characteristic histological findings, that is, diffuse and global glomerular accumulation of foamy macrophages and cytotoxic lymphocytes accompanied by the interaction of these cells as well as the exclusion of various differential diseases. Although there are no established therapeutic regimens, these patients receive various types of therapies, including high-dose glucocorticoids, immunosuppressants, or anti-interleukin-1 drug, and generally achieve favorable outcomes. We summarized the concept, diagnostic challenges, and recent topics of this disease entity and discussed treatment options based on our own experiences. Full article

The presence of an immunosuppressive tumour microenvironment in oesophageal adenocarcinoma (OAC) is a major contributor to poor responses. Novel treatment strategies are required to supplement current regimens and improve patient survival. This study examined the immunomodulatory effects that radiation therapy and chemokine receptor antagonism impose on T cell phenotypes in OAC with a primary goal of identifying potential therapeutic targets to combine with radiation to improve anti-tumour responses. Compared with healthy controls, anti-tumour T cell function was impaired in OAC patients, demonstrated by lower IFN-γ production by CD4⁺ T helper cells and lower CD8⁺ T cell cytotoxic potential. Such diminished T cell effector functions were enhanced following treatment with clinically relevant doses of irradiation. Interestingly, CCR5⁺ T cells were significantly more abundant in OAC patient blood compared with healthy controls, and CCR5 surface expression by T cells was further enhanced by clinically relevant doses of irradiation. Moreover, irradiation enhanced T cell migration towards OAC patient-derived tumour-conditioned media (TCM). In vitro treatment with the CCR5 antagonist Maraviroc enhanced IFN-γ production by CD4⁺ T cells and increased the migration of irradiated CD8⁺ T cells towards irradiated TCM, suggesting its synergistic therapeutic potential in combination with irradiation. Overall, this study highlights the immunostimulatory properties of radiation in promoting anti-tumour T cell responses in OAC and increasing T cell migration towards chemotactic cues in the tumour. Importantly, the CCR5 antagonist Maraviroc holds promise to be repurposed in combination with radiotherapy to promote anti-tumour T cell responses in OAC. Full article

New-Onset Diabetes Mellitus after Transplantation (NODAT) emerges as a prevalent complication post-kidney transplantation, with its incidence influenced by variations in NODAT definitions and follow-up periods. The condition’s pathophysiology is marked by impaired insulin sensitivity and β-cell dysfunction. Significant risk factors encompass age, gender, obesity, and genetics, among others, with the use of post-transplant immunosuppressants intensifying the condition. NODAT’s significant impact on patient survival and graft durability underscores the need for its prevention, early detection, and treatment. This review addresses the complexities of managing NODAT, including the challenges posed by various immunosuppressive regimens crucial for transplant success yet harmful to glucose metabolism. It discusses management strategies involving adjustments in immunosuppressive protocols, lifestyle modifications, and pharmacological interventions to minimize diabetes risk while maintaining transplant longevity. The importance of early detection and proactive, personalized intervention strategies to modify NODAT’s trajectory is also emphasized, advocating for a shift towards more anticipatory post-transplant care. Full article

Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug–drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression. Full article

Eculizumab is a monoclonal antibody blocking the terminal complement protein C5. As demonstrated in the phase III randomized, placebo-controlled, REGAIN clinical trial, eculizumab is efficacious in acetylcholine receptor antibody (AChR-Ab)-positive refractory generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America—MGFA class II–IV). It has not been studied in severe myasthenic exacerbation or myasthenic crisis (MGFA V). A 73-year-old man diagnosed with myasthenia gravis AChR-Ab positivity came to our observation for symptoms of bulbar and ocular weakness and unresponsiveness or intolerability to conventional immunosuppressive therapies (prednisone and azathioprine). Due to the recurrent clinical worsening with intubation over a short-term period, the patient was treated with eculizumab. After 15 days of eculizumab treatment, we observed a significant recovery of clinical condition. We discharged the patient to an outpatient regimen, where he is continuing with maintenance doses of eculizumab and slowly tapering steroid intake. The use of eculizumab in myasthenic crises is still anecdotal. Our case aims to provide eculizumab benefit for refractory severe gMG in a practical, real-world setting beyond the criteria of the REGAIN study. Further studies are needed to evaluate the efficacy and safety of eculizumab in myasthenic crises. Full article