Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and bone marrow aplasia of variable degrees. Thrombosis is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic measure for TEs in those individuals. Anticoagulants, such as warfarin and low-molecular-weight heparin, and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.

Invasive fungal diseases (IFDs) have been documented among the causes of post-chimeric antigen receptor-T (CAR-T) cell immunotherapy complications, with the incidence of IFDs in CAR-T cell therapy recipients being measured between 0% and 10%, globally. IFDs are notorious for their potentially life-threatening nature and challenging diagnosis and treatment. In this review, we searched the recent literature aiming to examine the risk factors and epidemiology of IFDs post-CAR-T infusion. Moreover, the role of antifungal prophylaxis is investigated. CAR-T cell therapy recipients are especially vulnerable to IFDs due to several risk factors that contribute to the patient’s immunosuppression. Those include the underlying hematological malignancies, the lymphodepleting chemotherapy administered before the treatment, existing leukopenia and hypogammaglobinemia, and the use of high-dose corticosteroids and interleukin-6 blockers as countermeasures for immune effector cell-associated neurotoxicity syndrome and cytokine release syndrome, respectively. IFDs mostly occur within the first 60 days following the infusion of the T cells, but cases even a year after the infusion have been described. Aspergillus spp., Candida spp., and Pneumocystis jirovecii are the main cause of these infections following CAR-T cell therapy. More real-world data regarding the epidemiology of IFDs and the role of antifungal prophylaxis in this population are essential.

Immune thrombocytopenia (ITP) in pediatric patients is a common cause of isolated thrombocytopenia. Various pathophysiological mechanisms are implicated in ITP pathogenesis, including the production of autoantibodies against components of platelets (PLTs) by B-cells, the activation of the complement system, phagocytosis by macrophages mediated by Fcγ receptors, the dysregulation of T cells, and reduced bone marrow megakaryopoiesis. ITP is commonly manifested with skin and mucosal bleeding, and it is a diagnosis of exclusion. In some ITP cases, the disease is self-limiting, and treatment is not required, but chronic-persistent disease can also be developed. In these cases, anti-CD20 monoclonal antibodies, such as rituximab and thrombopoietin (TPO) receptor agonists, can be used. TPO agonists have become standard of care today. It has been reported in the published literature that the efficacy of TPO-RAs can be up to 80% in the achievement of several end goals, such as PLT counts. In the current literature review, the data regarding the impact of TPO agonists in the pathogenesis of ITP and treatment outcomes of the patients are examined. In the era of precision medicine, targeted and individualized therapies are crucial to achieving better outcomes for pediatric patients with ITP, especially when chronic refractory disease is developed.

Low back pain (LBP) is a highly prevalent musculoskeletal problem and a leading cause of disability worldwide. From a pathophysiological perspective, the contribution of inflammation to LBP is being increasingly recognized. In this literature review, we aim to provide an overview of the role of inflammation as a mediator of LBP while summarizing clinical studies investigating the potential role of anti-inflammatory treatments in the management of LBP. Although often controversial, the available evidence suggests an important role of inflammation in the pathogenesis of LBP, which can be further translated into novel therapeutic targets. Both anti-tumor necrosis factor (anti-TNF) and anti-nerve growth factor (anti-NGF) agents hold the potential of blocking inflammation and pain pathways in patients with chronic LBP. TNF inhibitors have been tested mostly in small trials with mixed results, and their long-term efficacy remains to be proven. Anti-NGF agents have demonstrated stronger and consistent efficacy in randomized controlled trials, but safety concerns compromise their widespread use. The potential role of other anti-inflammatory molecules is currently under investigation. Presently, the routine use of TNF or NGF inhibitors is not supported in radiculopathy or chronic LBP. However, novel anti-inflammatory therapies introduced in the rheumatology field appear to be promising for specific subsets of patients suffering from chronic, refractory LBP, with a complementary role as therapeutic tools, after the unsuccessful outcome of the conservative approach.

This study evaluates the health-related quality of life (HRQoL) among patients with hemophilia A currently undergoing prophylactic treatment at the Hemophilia Center of Northern Greece. Using the Haem-A-QoL questionnaire, we assessed various HRQoL dimensions in a cohort of 29 adult male patients, analyzing the impact of age, disease severity, and treatment regimens. The results revealed that younger patients (18–30 years old) exhibited significantly better overall HRQoL scores (total score of 25.36) compared to older age groups (37.81 for the 31–45 group and 43.71 in the 45+ group), particularly in the physical health (29.16 vs. 48.43 vs. 58.57) and mental well-being domains (25 vs. 37.11 vs. 41.07). Interestingly, moderate hemophilia patients reported lower HRQoL (42.31) than those with severe form (34.85), suggesting unique challenges in managing their condition. The ’Sports/Free Time’ domain had the highest scores (65.81), indicating significant limitations in physical activities in the everyday lives of affected individuals. However, better outcomes were observed in the mental dimension (36.09), work/study (34.88), family planning (10.68), and relationships aspects (16.67), where our cohort reported very low scores compared to similar studies, indicating a significantly better quality of life in these domains. These findings highlight the importance of personalized psychosocial support and targeted interventions to address the specific needs of hemophilia patients, particularly in enhancing physical activity opportunities and managing the psychological burden of moderate hemophilia. The study contributes valuable insights into the HRQoL of hemophilia patients and underscores the necessity for tailored approaches to improve patient outcomes across all dimensions of life.

Rheumatoid arthritis (RA) is characterized by immune-mediated inflammation resulting in excess cardiovascular disease (CVD) risk. Increased sodium, decreased potassium intake and their ratio have been acknowledged as CVD risk modifiers, while pathophysiological studies suggest a role in autoimmunity and inflammation. We aimed to review in a systematic manner the literature regarding the effects of dietary sodium, potassium intake and their ratio, on cardiovascular and disease-related outcomes in patients with RA. We performed a systematic literature search in Medline and Cochrane. Our research concluded to 1,283 patients (8 studies). Although not all studies coincide, most agree that increased dietary sodium and reduced dietary potassium intake are adversely associated with disease related (rheumatic and immunologic) outcomes. The ratio between sodium and potassium emerges a potential indicator of autoimmunity state that needs to be further balanced. Only 4 studies reported associations with cardiovascular outcomes in RA, particularly hypertension, although not consistently and none with hard CVD endpoints. These findings support that interventions promoting a poor in sodium and rich in potassium diet in RA may have beneficial effects in terms of autoimmunity regulation, suppression of inflammation and improvement in cardiovascular health.