Search Results (2,342)

Multiple myeloma (MM) is predominantly a disease of the elderly. In recent years, a surge of highly effective plasma cell therapies has revolutionized the care of elderly multiple myeloma (MM) patients, for whom frailty and age-related competing causes of mortality determine management. Traditionally, the treatment of newly diagnosed elderly patients has centered on doublet or triplet combinations composed of immunomodulators (IMIDs), proteasome inhibitors (PIs), anti-CD38 monoclonal antibodies (mAbs), and corticosteroids producing median progression-free survival (PFS) rates between 34 and 62 months. However, recently, a series of large phase III clinical trials examining quadruplet regimens of PIs, IMIDs, corticosteroids, and anti-CD38 mAbs have shown exceptional outcomes, with median PFS exceeding 60 months, albeit with higher rates of peripheral neuropathy (≥Grade 2: 27% vs. 10%) when PIs and IMIDs are combined, and infections (≥Grade 3: 40% vs. 29–41%) with the addition of anti-CD38mAbs. The development of T-cell redirecting therapies including T-cell engagers (TCEs) and CAR-T cells has further expanded the therapeutic arsenal. TCEs have shown exceptional activity in relapsed disease and are being explored in the newly diagnosed setting with promising early results. However, concerns remain regarding the logistical challenges of step-up dosing, which often necessitates inpatient admission, the infectious risks, and the financial burden associated with TCEs in elderly patients. CAR-T, the most potent commercially available therapy for MM, offers the potential of a ‘one and done’ approach. However, its application to elderly patients has been tempered by significant concerns of cytokine release syndrome, early and delayed neurological toxicity, and its overall tolerability in frail patients. Robust data in frail patients are still needed. How CAR-T and TCEs will be sequenced among the growing therapeutic armamentarium for elderly MM patients remains to be determined. This review explores the safety, efficacy, cost, and logistical barriers associated with the above treatments in elderly MM patients. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Background/Objectives: Lysophosphatidylcholine (LPC) is composed of various lipid species, some of which exert pro-inflammatory and others anti-inflammatory activities. However, most of the LPC species analyzed to date are reduced in the serum of patients with inflammatory bowel disease (IBD) compared to healthy controls. To our knowledge, the correlation between serum LPC species levels and measures of inflammation, as well as their potential as markers for monitoring IBD activity, has not yet been investigated. Methods: Thirteen LPC species, varying in acyl chain length and number of double bonds, were measured in the serum of 16 controls and the serum of 57 patients with IBD. Associations with C-reactive protein (CRP) and fecal calprotectin levels as markers of IBD severity were assessed. Results: Serum levels of LPC species did not differ between the healthy controls and the entire patient cohort. In patients with IBD, serum levels of LPC 16:1, 18:0, 18:3, 20:3, and 20:5, as well as total LPC concentrations, showed inverse correlations with both CRP and fecal calprotectin levels, indicating an association with inflammatory activity. Nine LPC species were significantly reduced in patients with high fecal calprotectin compared to those with low values. LPC species with 22 carbon atoms and 4 to 6 double bonds were not related to disease activity. Stool consistency and gastrointestinal symptoms did not influence serum LPC profiles. Corticosteroid treatment was associated with lower serum LPC 20:3 and 22:5 levels, while mesalazine, anti-TNF, and anti-IL-12/23 therapies had no significant impact on LPC concentrations. There was a strong positive correlation between LPC species containing 15 to 18 carbon atoms and serum cholesterol, triglycerides, and phosphatidylcholine levels. However, there was no correlation with markers of liver disease. Conclusions: Shorter-chain LPC species are reduced in patients with active IBD and reflect underlying hypolipidemia. While these lipid alterations provide insight into IBD-associated metabolic changes, they appear unsuitable as diagnostic or disease monitoring biomarkers. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Background/Objectives: Pituitary tumors account for over 90% of all sellar region masses. However, a spectrum of rare neoplastic, inflammatory, infectious, and vascular lesions—benign and malignant—can arise in the intra- and parasellar compartments and clinically and radiologically mimic PitNETs. We report a cohort of 47 such rare and cystic midline intracranial lesions, emphasizing their distinctive morphological, clinical, and imaging features and the personalized treatment strategies applied. Methods: In this retrospective single-center study, we reviewed all patients treated for suspected PitNETs via transsphenoidal approach between 2015 and 2024. Of 529 surgical cases, we excluded confirmed PitNETs, meningiomas, and classical intradural craniopharyngiomas. Collected data encompassed patient demographics, tumor characteristics, presenting symptoms, extent of resection or medical therapy, endocrine outcomes, and follow-up information. Results: Among all 529 patients who underwent surgical treatment for sellar lesions from 2015 to 2024, 47 cases (8.9%) were identified as rare or cystic masses. Forty-six underwent transsphenoidal resection; one patient with hypophysitis received corticosteroid therapy alone. Presenting symptoms included headache (n = 16), dizziness (n = 5), oculomotor disturbances (n = 2), and visual impairment (n = 17). Endocrine dysfunction was found in 30 patients, 27 of whom required hydrocortisone replacement. Histopathological diagnoses were led by colloid cysts (n = 14) and Rathke’s cleft cysts (n = 11). The remaining 22 cases comprised plasmacytoma, germinoma, lymphoma, pituicytoma, inverted papilloma, metastatic carcinoma, chordoma, nasopharyngeal carcinoma, chloroma, and other rare entities. Preoperative imaging diagnosis proved incorrect in 38% (18/47) of cases, with several lesions initially misidentified as PitNETs. Conclusions: Nearly 9% of presumed PitNETs were rare, often benign or inflammatory lesions requiring distinct management. Most could be safely resected and demonstrated excellent long-term outcomes. Yet, despite advanced imaging techniques, accurate preoperative differentiation remains challenging, with over one-third misdiagnosed. Clinical red flags—such as early hormone deficits, rapid progression or atypical imaging findings—should prompt early interdisciplinary evaluation and, when indicated, image-guided biopsy to avoid unnecessary surgery and ensure tailored therapy. Full article

Eosinophilic Granulomatosis with Polyangiitis (EGPA) is a rare systemic vasculitis with eosinophilic inflammation and variable clinical presentations. Although skin manifestations are frequent, current classification criteria do not include them, which may underestimate their diagnostic value. This prospective observational study aimed to assess systemic and skin involvement as well as eosinophilia, anti-neutrophil cytoplasmic antibody (ANCA), and Anti-nuclear antibodies (ANA) serum levels in 20 EGPA patients followed for one year at the University Hospital of Messina, Italy, before starting Mepolizumab, 300 mg. Eosinophilia, ANCA status, systemic and skin involvement were also evaluated at 6 and 12 months; a literature review on these data supplements our findings. Skin involvement was present in 55% of patients, including purpura, urticarial vasculitis, angioedema, maculopapular rash, and nodules, mostly in ANCA-negative patients, though purpura was more frequent in ANCA-positive cases but without any statistically significant correlation. ANAs were present in 50% of patients, together with ANCA in two subjects and without in eight. Mepolizumab significantly reduced eosinophil levels, BVASs, and corticosteroid dependence, with notable improvement in skin symptoms. In conclusion, skin manifestations are common in EGPA and may represent useful indicators of disease activity. Their integration with ANCA status, eosinophil counts, and positivity to other autoantibodies could enhance diagnostic and monitoring strategies identifying different clusters of EGPA patients even if the small sample size limits the generalizability of the findings. Full article

Background: Treatment compliant with the Global Initiative for Asthma (GINA) can promote more effective disease control. Single-inhaler triple therapy (SITT) is one method that is used to optimize therapy in this context, but TRIPLE therapy is still employed by physicians to a limited extent. Objective: This study aimed to describe the factors influencing challenges in optimizing asthma therapy. Methods: A 19-question survey, created via the CATI system, was distributed among pulmonologists, allergologists, general practitioners, and internal medicine specialists in Poland, Greece, Sweden, Slovenia, and Austria. Results: Statistically significant percentage differences in the use of TRIPLE therapy in the context of asthma management were observed among countries as well as between pulmonologists, allergists, and other specialists. Overuse of oral corticosteroids (OCSs) to treat nonsevere and severe asthma in the absence of an approach that focuses on optimizing inhalation therapy among asthma patients receiving TRIPLE therapy was observed in different countries as well as among physicians with different specialties. Twenty elements associated with the challenges involved in diagnosing and managing difficult-to-treat and severe asthma were identified. Six clinical categories for the optimization of asthma therapy via SITT were highlighted. The degree of therapeutic underestimation observed among severe asthma patients was assessed by comparing actual treatment with the recommendations of the GINA 2023 guidelines. Conclusions: Physicians of various specialties in Europe are subject to therapeutic inertia in terms of their compliance with the GINA 2023 guidelines. Full article

Antibody-mediated autoimmune diseases are common, can involve any organ system, and pose a large burden for patients and healthcare systems. Most antibody-mediated diseases are mediated by IgG antibodies. Selective targeting of pathogenic antibodies is an attractive treatment option which has already proven to be effective in antibody-positive generalized myasthenia gravis, maternal-fetal alloimmune cytopenias, and immune thrombocytopenic purpura. Warm autoimmune hemolytic anemia (wAIHA) is an autoimmune disorder mediated by pathogenic antibodies mainly of the IgG class with no approved therapy. Current treatment includes non-specific immunosuppression with corticosteroids, rituximab, and other immunosuppressive agents. With most therapies, time to response can be delayed and transfusions may be needed. Neonatal Fc receptor (FcRN) therapies provide rapid and sustained reduction of pathogenic IgG levels providing potential for fast, effective therapy in antibody-mediated autoimmune diseases including warm autoimmune hemolytic anemia. This review focuses on the emerging role of FcRn inhibition in autoimmune hematologic diseases, and their therapeutic potential in wAIHA. Full article

Background and Clinical Significance: Infective endocarditis (IE) is a serious condition with rising incidence, frequently caused by Staphylococcus aureus. However, cases involving rare congenital anomalies such as Gerbode’s defect are uncommon. Case Presentation: This report presents the first documented case of IE in a patient with a congenital Gerbode defect complicated by DRESS syndrome—a severe, drug-induced hypersensitivity reaction typically triggered by antibiotics like oxacillin. A 65-year-old woman developed infective endocarditis involving vegetations on the cardiac device lead, the tricuspid valve, and adjacent to a Gerbode defect. The diagnosis was confirmed by positive blood cultures and echocardiographic findings. She received treatment with oxacillin. Subsequently, she exhibited clinical features consistent with DRESS syndrome, including rash, eosinophilia, and multi-organ involvement. Rapid recognition and management, including corticosteroid therapy and antibiotic modification, led to clinical improvement. Conclusions: This case highlights the importance of vigilance for DRESS syndrome in prolonged antibiotic therapy for IE, especially in the context of rare congenital cardiac anomalies. In addition, guidelines are needed to optimize the diagnosis and treatment of this potentially lethal complication. Full article

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Background: Oral lichen planus is a chronic, potentially malignant disorder affecting the mucous membrane. As the etiology remains not fully understood, the treatment of this condition is mainly symptomatic, involving corticosteroids and other immunosuppressive agents, e.g., calcineurin inhibitors. One of the alternative therapeutic approaches includes platelet concentrates, which are autologous bioactive materials. The aim of this review was to evaluate the effects of platelet concentrates in the treatment of oral lichen planus and to compare them to other therapeutic strategies. Methods: The electronic databases PubMed/Medline, Web of Science, and Cochrane Library were searched for articles published up to 30 March 2025, describing clinical studies focused on oral lichen planus and treatment with platelet concentrates. Results: Fourteen studies describing the effects of oral lichen planus therapy with three types of platelet concentrates (injectable platelet-rich plasma, injectable platelet-rich fibrin, and platelet-rich plasma gel) were included in this review. Comparative strategies included steroids and immunosuppressive agents. The treatment duration ranged from 3 weeks to 2 months. The follow-up period varied from 4 weeks to 6 months. In most of the studies, comparable efficacy was achieved for platelet derivatives and alternative treatments. Two of the studies demonstrated more beneficial effects for platelet concentrates compared to controls, while in one of the studies, more severe adverse reactions were revealed in the platelet group compared to the controls. Conclusions: Autologous platelet concentrates showed comparable efficacy in achieving clinical improvement in patients with oral lichen planus to steroids and immunosuppressive drugs. Platelet derivatives could be considered as an alternative treatment to topical immunosuppressives, especially in steroid-refractory cases. Full article

Crohn’s disease is a chronic inflammation affecting the gastrointestinal tract. To date, patients are commonly treated with corticosteroids or more aggressive biologics for high-risk subjects. Stem Cell Educator therapy has been successfully utilized to treat patients with type 1 diabetes and other autoimmune conditions. A 78-year-old patient with long-standing Crohn’s disease received one treatment with the Stem Cell Educator therapy, followed by clinical, radiographic, pathological examinations and immune marker testing by flow cytometry. After the treatment with Stem Cell Educator therapy, the patient’s clinical symptoms were quickly improved with normal bowel movements, without abdominal pain or rectal bleeding. Flow cytometry analysis revealed a marked decline in inflammatory markers, such as the percentage of monocyte/macrophage-associated cytokine interleukin-1 beta (IL-1β)⁺ cells, which reduced from 94.98% at the baseline to 18.21%, and down-regulation of the percentage of chemokine CXCL16⁺ cells from 91.92% at baseline to 42.58% at 2-month follow-up. Pathologic examination of the biopsy specimens from colonoscopy five weeks and six months post-treatment showed ileal mucosa with no specific abnormality and no significant inflammation or villous atrophy; no granulomas were identified. A follow-up CT scan four and one-half months post-treatment showed no evidence of the previously seen stenosis of the ilio-colonic anastomosis with proximal dilatation. Stem Cell Educator therapy markedly reduced inflammation in the subject with Crohn’s disease, leading to durable clinical, immunological, radiographic, and pathological improvements. Full article

Acne vulgaris is a multifactorial inflammatory skin disorder that significantly impairs quality of life and may signal underlying systemic dysfunction, particularly in adult women with treatment-resistant or atypical presentations. This case series presents three clinically and etiologically distinct examples of persistent acne in female patients, each associated with different contributing factors: long-term topical corticosteroid misuse, polycystic ovary syndrome (PCOS), and metabolic syndrome with autoimmune thyroiditis. All cases underwent comprehensive dermatologic evaluation, endocrine/metabolic assessments, and personalized therapeutic interventions, ranging from corticosteroid withdrawal and barrier repair to hormonal modulation and insulin-sensitizing therapy. Clinical progression was monitored for up to six months, revealing favorable responses in all cases, with substantial lesion clearance and improved skin quality. These real-world cases highlight the importance of an integrative, interdisciplinary diagnostic approach in refractory acne and support the need for individualized, long-term management strategies tailored to underlying systemic contributors. Full article

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and individual patient data meta-analysis of published cases of dengue-associated HLH. Eligible studies were identified through a search of PubMed and Scopus databases up to 5 March 2025. Clinical, laboratory, microbiological, treatment, and outcome data were extracted and analyzed. Results: A total of 133 patients from 71 studies were included. The median patient age was 18 years, and 56.8% were male. Common clinical features included fever (96.9%), cytopenias, organomegaly, and liver dysfunction. ALT elevation, jaundice, and hypofibrinogenemia were associated with mortality. DENV-1 was the most common serotype (57.4%) and was negatively associated with death. Overall, 19.3% of patients died. Multivariate analysis did not identify independent mortality predictors. Conclusions: Dengue-associated HLH predominantly affects young individuals and carries significant mortality. Key indicators of poor prognosis include hepatic dysfunction and the presence of shock or organ failure. Early recognition and prompt immunomodulatory treatment, particularly corticosteroids, may improve outcomes. Full article

Aspergillus can cause a spectrum of diseases depending on the immune status and predisposing conditions. Invasive pulmonary aspergillosis (IPA) is classically seen in patients with severe immunocompromise, such as patients with hematologic malignancies, transplant recipients, and chronic corticosteroid use at high doses. Recently, IPA cases in patients without these classic risk factors, including those associated with severe respiratory viral infections, chronic obstructive pulmonary disease, liver failure, and critical illness, are being increasingly recognized. Delayed recognition and missed diagnoses contribute to increased mortality in these patient populations. Maintaining a high index of suspicion and implementation of systematic screening protocols in high-risk patients may help reduce missed or delayed diagnoses and improve patient outcomes. This review describes the pathophysiology, incidence, risk factors, outcomes, and diagnostic and treatment considerations in IPA in patients with emerging risk factors. Full article