Therapeutic Options Research Articles

Therapeutic challenges and unmet needs in the management of myasthenia gravis: an Italian expert opinion.

Myasthenia gravis (MG) is a rare, autoimmune, neurological disorder. Most MG patients have autoantibodies against acetylcholine receptors (AChRs). Some have autoantibodies against muscle-specific tyrosine kinase (MuSK) or lipoprotein-receptor-related protein 4 (LRP4), and some are seronegative. Standard of care, which includes anti-cholinesterase drugs, thymectomy, corticosteroids (CS), and off-label use of non-steroidal immunosuppressive drugs (NSISTs), is bounded by potential side effects and limited efficacy in refractory generalized MG (gMG) patients. This highlights the need for new therapeutic approaches for MG. Eculizumab, a monoclonal antibody that inhibits the complement system, has been recently approved in Italy for refractory gMG. A panel of 11 experts met to discuss unmet therapeutic needs in the acute and chronic phases of the disease, as well as the standard of care for refractory patients. Survival was emphasized as an acute phase outcome. In the chronic phase, persistent remission and early recognition of exacerbations to prevent myasthenic crisis and respiratory failure were considered crucial. Refractory patients require treatments with fast onset of action, improved tolerability, and the ability to slow disease progression and increase life expectancy. The Panel agreed that eculizumab would presumably meet the therapeutic needs of many refractory gMG patients. The panel concluded that the unmet needs of current standard of care treatments for gMG are significant. Evaluating new therapeutic options accurately is essential to find the best balance between efficacy and tolerability for each patient. Collecting real-world data on novel molecules in routine clinical practice is necessary to address unmet needs.

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model

The ligands of chemokine receptors 2 and 5 (CCR2 and CCR5, respectively) are associated with the pathomechanism of neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, the aim of our study was to examine the function of these factors in the hypersensitivity accompanying diabetes. Additionally, we analyzed the analgesic effect of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, and its influence on the effectiveness of morphine. An increasing number of experimental studies have shown that targeting more than one molecular target is advantageous compared with the coadministration of individual pharmacophores in terms of their analgesic effect. The advantage of using bifunctional compounds is that they gain simultaneous access to two receptors at the same dose, positively affecting their pharmacokinetics and pharmacodynamics and consequently leading to improved analgesia. Experiments were performed on male and female Swiss albino mice with a streptozotocin (STZ, 200 mg/kg, i.p.) model of diabetic neuropathy. We found that the blood glucose level increased, and the mechanical and thermal hypersensitivity developed on the 7th day after STZ administration. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7, while in female mice, we observed additional increases in Ccl8 and Ccl12 levels. We have demonstrated for the first time that a single administration of cenicriviroc relieves pain to a similar extent in male and female mice. Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients.

Primary Presacral Neuroendocrine Tumors Presented by Lumbosacral Pain: a Case Report

Primary presacral neuroendocrine tumors (NETs) are exceedingly rare and often present with extensive metastases, posing significant challenges for clinical management. We report a case of a presacral neuroendocrine tumor in a 68-year-old male who presented with lumbosacral pain. Enhanced MRI revealed a soft tissue mass at the sacrococcygeal region, while whole-body enhanced 18F-PET/CT identified small intratumoral vessels and involvement of the adjacent rectal posterior wall, mesorectal fascia, presacral fascia, and sacrococcygeal bones, accompanied by multiple lymph node metastases and widespread metastases to the lungs, liver, and bones. A CT-guided biopsy confirmed the diagnosis of a grade 2 (G2) neuroendocrine tumor. Given the tumor's extensive metastasis and aggressive nature, surgical intervention was deemed unsuitable, and the patient was treated with sulfatinib. Sulfatinib shows significant potential in managing advanced neuroendocrine tumors, providing an effective therapeutic option for patients with such complex and high-risk conditions.

A New Application for Cenicriviroc, a Dual CCR2/CCR5 Antagonist, in the Treatment of Painful Diabetic Neuropathy in a Mouse Model.

The ligands of chemokine receptors 2 and 5 (CCR2 and CCR5, respectively) are associated with the pathomechanism of neuropathic pain development, but their role in painful diabetic neuropathy remains unclear. Therefore, the aim of our study was to examine the function of these factors in the hypersensitivity accompanying diabetes. Additionally, we analyzed the analgesic effect of cenicriviroc (CVC), a dual CCR2/CCR5 antagonist, and its influence on the effectiveness of morphine. An increasing number of experimental studies have shown that targeting more than one molecular target is advantageous compared with the coadministration of individual pharmacophores in terms of their analgesic effect. The advantage of using bifunctional compounds is that they gain simultaneous access to two receptors at the same dose, positively affecting their pharmacokinetics and pharmacodynamics and consequently leading to improved analgesia. Experiments were performed on male and female Swiss albino mice with a streptozotocin (STZ, 200 mg/kg, i.p.) model of diabetic neuropathy. We found that the blood glucose level increased, and the mechanical and thermal hypersensitivity developed on the 7th day after STZ administration. In male mice, we observed increased mRNA levels of Ccl2, Ccl5, and Ccl7, while in female mice, we observed additional increases in Ccl8 and Ccl12 levels. We have demonstrated for the first time that a single administration of cenicriviroc relieves pain to a similar extent in male and female mice. Moreover, repeated coadministration of cenicriviroc with morphine delays the development of opioid tolerance, while the best and longest-lasting analgesic effect is achieved by repeated administration of cenicriviroc alone, which reduces pain hypersensitivity in STZ-exposed mice, and unlike morphine, no tolerance to the analgesic effects of CVC is observed until Day 15 of treatment. Based on these results, we suggest that targeting CCR2 and CCR5 with CVC is a potent therapeutic option for novel pain treatments in diabetic neuropathy patients.

Novel Antibiotics for Gram-Negative Nosocomial Pneumonia

Nosocomial pneumonia, including hospital-acquired pneumonia and ventilator-associated pneumonia, is the leading cause of death related to hospital-acquired infections among critically ill patients. A growing proportion of these cases are attributed to multi-drug-resistant (MDR-) Gram-negative bacteria (GNB). MDR-GNB pneumonia often leads to delayed appropriate treatment, prolonged hospital stays, and increased morbidity and mortality. This issue is compounded by the increased toxicity profiles of the conventional antibiotics required to treat MDR-GNB infections. In recent years, several novel antibiotics have been licensed for the treatment of GNB nosocomial pneumonia. These novel antibiotics are promising therapeutic options for treatment of nosocomial pneumonia by MDR pathogens with certain mechanisms of resistance. Still, antibiotic resistance remains an evolving global crisis, and resistance to novel antibiotics has started emerging, making their judicious use crucial to prolong their shelf-life. This article presents an up-to-date review of these novel antibiotics and their current role in the antimicrobial armamentarium. We critically present data for the pharmacokinetics/pharmacodynamics, the in vitro spectrum of antimicrobial activity and resistance, and in vivo data for their clinical and microbiological efficacy in trials. Where possible, available data are summarized specifically in patients with nosocomial pneumonia, as this cohort may exhibit ‘critical illness’ physiology that affects drug efficacy.

Discrete Choice Experiments to Elicit Patient Preferences for the Treatment of Major Depressive Disorder: A Systematic Review.

Individual preferences for treatment options for major depressive disorder can impact therapeutic decision making, adherence, and ultimately outcomes. This systematic review of discrete choice experiments (DCEs) on patient preferences for major depressive disorder treatment assessed the range of DCE applications in major depressive disorder to document patient stakeholder involvement in DCE development and to identify the relative importance of treatment attributes. We searched MEDLINE via Ovid (1946-present), EMBASE (Elsevier interface), Cochrane Central Register of Controlled Trials (Wiley interface), and PsycINFO (EBSCO interface) databases on 29 May, 2024. Covidence software facilitated the review, which four members completed independently. The review was conducted in two phases: title and abstract and then a full-text review. We used an established quality reporting tool to evaluate selected articles. The Covidence extraction tool was adapted for this study. A total of 19 articles were included in this review. Most studies elicited preferences for depression treatment (63.2%) and care delivery (10.5%). Two assessed willingness to pay. Individuals prefer a combination of medicine and counseling over each treatment alone. Treatment efficacy, relapse prevention, and symptom relief were among the most important attributes. Individuals were willing to accept larger risks to achieve symptom improvement. Few studies examined preference heterogeneity with latent subgroups. Discrete choice experiments for major depressive disorder treatment preferences enable an assessment of trade-offs for first-line therapeutic options. Patient stakeholders are infrequently involved as collaborators in the DCE development. Few examined preference heterogeneity among subgroups.

Toward a cure - Advancing HIV/AIDs treatment modalities beyond antiretroviral therapy: A Review.

Antiretroviral therapy, also known as antiretroviral therapy (ART), has been at the forefront of the ongoing battle against human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDs). ART is effective, but it has drawbacks such as side effects, medication resistance, and difficulty getting access to treatment, which highlights the urgent need for novel treatment approaches. This review explores the complex field of HIV/AIDS treatment, covering both established alternative treatment modalities and orthodox antiretroviral therapy. Numerous reliable databases were reviewed, including PubMed, Web of Science, Scopus, and Google Scholar. The results of a thorough literature search revealed numerous therapeutic options, including stem cell transplantation, immunotherapy, gene therapy, latency reversal agents, and pharmaceutical vaccinations. While gene therapy has promise for altering cellular resistance to infection and targeting HIV-positive cells, immunotherapy treatments seek to strengthen the immune system's ability to combat HIV. Latency reversal agents offer a promising method of breaking the viral latency and making infected cells vulnerable to immune system destruction or antiretroviral drugs. Furthermore, there is potential for improving immune responses against HIV using medical vaccinations. This review stresses the vital significance of ongoing research and innovation in the hunt for a successful HIV/AIDS treatment through a thorough examination of recent developments and lingering challenges. The assessment notes that even though there has been tremendous progress in treating the illness, there is still more work to be done in addressing current barriers and investigating various treatment options in order to achieve the ultimate objective of putting an end to the HIV/AIDS pandemic.

Developing Interventions for Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is an incurable, progressive respiratory disease that may have a significant negative impact on the morbidity and mortality of affected patients. A substantial portion of the world's population is affected by COPD, and despite optimal medical management with medications, supplemental oxygen, and pulmonary rehabilitation, many patients are left debilitated because of this disease. Bronchoscopic treatment modalities offer a less-invasive method for the treatment of refractory COPD compared to surgical interventions and have expanded the potential therapeutic options for these patients. Bronchoscopic lung volume reduction is aimed at decreasing the hyperinflation and air trapping that occur in emphysema, and the most studied and successful intervention is endobronchial valve placement. Endobronchial coils, polymeric sealants, and thermal ablation are other researched alternatives. Additional interventional procedures are being investigated for the treatment of the mucus hypersecretion and cough that are associated with the chronic bronchitis phenotype of COPD and include targeted lung denervation, metered dose spray cryotherapy, deobstruction balloon, and bronchial rheoplasty. This review summarizes the most recent evidence pertaining to available therapies for the management of COPD, including chronic bronchitis, with a particular focus on bronchoscopic interventions.

Light Therapy in Post-Traumatic Stress Disorder: A Systematic Review of Interventional Studies.

Background: Due to limitations in treatment strategies for post-traumatic stress disorders (PTSD), therapeutic options such as light therapy (LT) have garnered some interest in recent years. We aimed to review the effectiveness of LT in patients with PTSD. Methods: Using PubMed, PsycINFO, Web of Science, the Cochrane database, ClinicalTrials.gov, and PTSDpubs, we systematically searched for papers assessing the effect of LT in PTSD. We evaluated the risk of bias of included studies using the Cochrane handbook, and synthesized our findings following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (PRISMA 2020). Results: From 140 initial papers, we included four randomized controlled trials (RCTs) and one single-arm study. The study sample size ranged between 15 and 82, the mean age (standard deviation) varied between 31.4 (8.8) and 44.9 (11.8) years, and LT was applied for four or six weeks. The risk of bias was low in three studies, and of some concern in the two other trials. Most studies reported no significant differences between LT and placebo regarding effects on subjective (sleep quality and insomnia severity) and objective sleep parameters. LT was associated with a significant improvement in PTSD symptom severity in the single-arm study and two RCTs, as well as a greater retention of extinction learning. Results on depression and anxiety were discrepant. Conclusions: This review revealed that relevant studies are scarce, with promising findings concerning PTSD symptoms, but inconsistencies for the other parameters. Further research projects are needed to better explore this topic.

Arnicolide D Inhibits Proliferation and Induces Apoptosis of Osteosarcoma Cells through PI3K/Akt/mTOR Pathway.

Osteosarcoma is considered as the most prevalent form of primary malignant bone cancer, prompting a pressing need for novel therapeutic options. Arnicolide D, a sesquiterpene lactone derived from the traditional Chinese herbal medicine Centipeda minima (known as E Bu Shi Cao in Chinese), showed anticancer efficacy against several kinds of cancers. However, its effect on osteosarcoma remains unclear. This study aimed to investigate the anticancer activity of arnicolide D and the underlying molecular mechanism of its action in osteosarcoma cells, MG63 and U2OS. Cell viability and proliferation were evaluated through MTT assay and colony formation assay following 24 h and 48 h treatment with different concentrations of arnicolide D. Flow cytometry was employed to examine cell cycle progression and apoptosis after 24 h treatment of arnicolide D. Western blotting was performed to determine the expression of the PI3k, Akt and m-TOR and their phosphorylated forms. Our findings revealed that arnicolide D treatment resulted in a significant reduction in cell viability, the inhibition of proliferation, and the induction of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, arnicolide D could inhibit the activation of PI3K/Akt/mTOR pathway in osteosarcoma cells. Based on our results, arnicolide D demonstrated significant anti-osteosarcoma activity and held the potential to be considered as a therapeutic candidate for osteosarcoma in the future.

Repurposing of dibucaine and niflumic acid as antimicrobial agents in combination with antibiotics against Staphylococcus aureus.

The versatile human commensal bacteria and pathogen Staphylococcus aureus cause several community and hospital-acquired illnesses associated with significant morbidity and death. Antibiotic therapy for S. aureus infections has grown increasingly difficult as the organism has developed a wide spectrum of antibiotic resistance mechanisms. This situation emphasizes the significance of developing and advocating new antimicrobials for preventative and therapeutic measures. Our study aimed to identify and evaluate new therapeutic options against S. aureus. We investigated the efficacy of two drugs, dibucaine, and niflumic acid, as potential adjuvant for anti-staphylococcal therapeutics. Dibucaine and niflumic acid found to have bactericidal activity against S. aureus. These drugs acted synergistically with antibiotics reducing the required dose of antibiotics up to 4 times. In combination with antibiotics, they were effectively and synergistically inhibited the formation of biofilms of S. aureus. The best synergistic partner of dibucaine was with kanamycin and tetracycline, whereas niflumic acid was with streptomycin and ampicillin. Both the drugs showed significant efflux inhibition in the bacteria. Moreover, the drugs are found to be safe at synergistic doses. Our findings suggest that dibucaine and niflumic acid could be potential adjuvant with antibiotics for the treatment of S. aureus infections. Their ability to significantly enhance the efficacy of antibiotics highlights their potential clinical significance as adjunct therapies.

[Translated article] Total hip arthroplasty with second generation dual mobility system as a treatment for primary coxarthrosis, medium-term results

IntroductionOsteoarthritis is a disabling pathology characterised by joint pain and stiffness. A prevalence of coxarthrosis of 7.4% is reported in our country. Total hip joint replacement is indicated in advanced stages, a procedure that is not free of complications, the most frequent being prosthetic dislocation, which can be prevented with dual mobility systems. The following study aims to determine the rate of complications and clinical outcomes in dual mobility systems in primary coxarthrosis. Materials and methodsA retrospective study included 120 cases in 114 patients diagnosed with grade III coxarthrosis, mean age was 62.43 years, with a mean follow-up of 4.5 years. Joint replacement was performed by Hardinge approach. All cases were assessed clinically using the Harris Hip Score (HHS) and radiologically to demonstrate mid-term results. ResultsThe preoperative value on the HHS scale had a mean of 56.45, postoperative at one month 74.23; 6 months 85.40; 1 year 94.01 and at 5 years 94.84 points, representing a functional improvement of 17.78 postoperative month; 28.95 at 6 months postoperative; 37.56 at one year postoperative and 38.39 points at 5 years postoperative. A complication rate of 3.44%; 0.86% of complications were associated with the prosthetic components. ConclusionThe dual mobility system should be considered as a therapeutic option in primary hip joint replacement due to excellent functional results and low complication rates. Evidence levelIV. Retrospective observational case series study.

Targeted delivery of CEBPA-saRNA for the treatment of pancreatic ductal adenocarcinoma by transferrin receptor aptamer decorated tetrahedral framework nucleic acid

Pancreatic cancer, predominantly pancreatic ductal adenocarcinoma (PDAC), remains a highly lethal malignancy with limited therapeutic options and a dismal prognosis. By targeting the underlying molecular abnormalities responsible for PDAC development and progression, gene therapy offers a promising strategy to overcome the challenges posed by conventional radiotherapy and chemotherapy. This study sought to explore the therapeutic potential of small activating RNAs (saRNAs) specifically targeting the CCAAT/enhancer-binding protein alpha (CEBPA) gene in PDAC. To overcome the challenges associated with saRNA delivery, tetrahedral framework nucleic acids (tFNAs) were rationally engineered as nanocarriers. These tFNAs were further functionalized with a truncated transferrin receptor aptamer (tTR14) to enhance targeting specificity for PDAC cells. The constructed tFNA-based saRNA formulation demonstrated exceptional stability, efficient saRNA release ability, substantial cellular uptake, biocompatibility, and nontoxicity. In vitro experiments revealed successful intracellular delivery of CEBPA-saRNA utilizing tTR14-decorated tFNA nanocarriers, resulting in significant activation of tumor suppressor genes, namely, CEBPA and its downstream effector P21, leading to notable inhibition of PDAC cell proliferation. Moreover, in a mouse model of PDAC, the tTR14-decorated tFNA-mediated delivery of CEBPA-saRNA effectively upregulated the expression of the CEBPA and P21 genes, consequently suppressing tumor growth. These compelling findings highlight the potential utility of saRNA delivered via a designed tFNA nanocarrier to induce the activation of tumor suppressor genes as an innovative therapeutic approach for PDAC.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to liveconditionandlifesafety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum it all up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.&#xD.

Anal Fissure and Its Treatments: A Historical Review.

Anal fissure is one of the most common proctological pathologies. It consists of the formation of a longitudinal tear in the anoderm, causing pain and bleeding during and after defecation. When chronic, it can significantly negatively impact the quality of life of the affected patient. Currently, multiple therapeutic options are available, both medical and surgical. The objective of this article is to highlight the historical evolution in the physiopathological understanding and treatment of this disease, underlining the key moments in this history. This is the first article to summarize the milestones in the treatment of anal fissure from ancient to current times.

Treatment modification patterns of glucose-lowering agents in Saudi Arabia: A retrospective real-world data analysis

AimThe growing number of antidiabetics has broadened therapeutic options, leading to heterogeneity in prescribing patterns. Studies identifying antidiabetics modification patterns are lacking in Saudi Arabia. Therefore, the aim of this study is to describe modification patterns in Saudi patients. MethodsPatients ≥ 18 years old with at least one antidiabetic between 2016 and 2022 were included. Follow-up started from the earliest to the last prescription.Two modification types were evaluated: “add-on,” prescribing new antidiabetics within a treatment episode, and “switching”, starting a new treatment episode after the preceding ends. Descriptive statistics were used to characterize patients and estimate events proportions. ResultsOf 122,291 patients, 47.2 % had treatment interruption or modification, totaling 303,781 events. Interruptions accounted for 54 %, add-on for 11 %, and switching for 35 %. The median time to first event was 159 days. The most add-on included dipeptidyl peptidase-4 inhibitor (DPP-4) inhibitors to biguanide and sulfonylurea (8 %), and sulfonylurea to biguanide (8 %). Among 106,405 switching events, 23 % shifted from dual to monotherapy and 17 % from monotherapy to dual therapy. ConclusionNearly half of patients experienced modifications or interruptions, with notable shifts between monotherapies and dual therapies. These findings highlight the evolving landscape of treatment patterns in Saudi Arabia and guide future research and decision-making.

Unique immune characteristics and differential anti-PD-1-mediated reinvigoration potential of CD8+ TILs based on BRCA1/2 mutation status in epithelial ovarian cancers

BackgroundWe aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations status and differential PD-1 expression levels.MethodsTumor-infiltrating lymphocytes (TILs)...

DAMP-ing IBD: Extinguish the Fire and Prevent Smoldering.

In inflammatory bowel diseases (IBD), the most promising therapies targeting cytokines or immune cell trafficking demonstrate around 40% efficacy. As IBD is a multifactorial inflammation of the intestinal tract, a single-target approach is unlikely to solve this problem, necessitating an alternative strategy that addresses its variability. One approach often overlooked by the pharmaceutically driven therapeutic options is toaddress the impact of environmental factors. This is somewhat surprising considering that IBD is increasingly viewed as a condition heavily influenced by such factors, including diet, stress, and environmental pollution-often referred to as the "Western lifestyle". In IBD, intestinal responses result from a complex interplay among the genetic background of the patient, molecules, cells, and the local inflammatory microenvironment where danger- and microbe-associated molecular patterns (D/MAMPs) provide an adjuvant-rich environment. Through activating DAMP receptors, this array of pro-inflammatory factors can stimulate, for example, the NLRP3 inflammasome-a major amplifier of the inflammatory response in IBD, and various immune cells via non-specific bystander activation of myeloid cells (e.g., macrophages) and lymphocytes (e.g., tissue-resident memory T cells). Current single-target biological treatment approaches can dampen the immune response, but without reducing exposure to environmental factors of IBD, e.g., by changing diet (reducing ultra-processed foods), the adjuvant-rich landscape is never resolved and continues to drive intestinal mucosal dysregulation. Thus, such treatment approaches are not enough to put out the inflammatory fire. The resultant smoldering, low-grade inflammation diminishes physiological resilience of the intestinal (micro)environment, perpetuating the state of chronic disease. Therefore, our hypothesis posits that successful interventions for IBD must address the complexity of the disease by simultaneously targeting all modifiable aspects: innate immunity cytokines and microbiota, adaptive immunity cells and cytokines, and factors that relate to the (micro)environment. Thus the disease can be comprehensively treated across the nano-, meso-, and microscales, rather than with a focus on single targets. A broader perspective on IBD treatment that also includes options to adapt the DAMPing (micro)environment is warranted.

Demystifying the potential of lipid-based nanocarriers in targeting brain malignancies.

Drug targeting for brain malignancies is restricted due to the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which act as barriers between the blood and brain parenchyma. Certainly, the limited therapeutic options for brain malignancies have made notable progress with enhanced biological understanding and innovative approaches, such as targeted therapies and immunotherapies. These advancements significantly contribute to improving patient prognoses and represent a promising shift in the landscape of brain malignancy treatments. A more comprehensive understanding of the histology and pathogenesis of brain malignancies is urgently needed. Continued research focused on unraveling the intricacies of brain malignancy biology holds the key to developing innovative and tailored therapies that can improve patient outcomes. Lipid nanocarriers are highly effective drug delivery systems that significantly improve their solubility, bioavailability, and stability while also minimizing unwanted side effects. Surface-modified lipid nanocarriers (liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, lipid nanocapsules, lipid-polymer hybrid nanocarriers, lipoproteins, and lipoplexes) are employed to improve BBB penetration and uptake through various mechanisms. This systematic review illuminates and covers various topics related to brain malignancies. It explores the different methods of drug delivery used in treating brain malignancies and delves into the benefits, limitations, and types of brain-targeted lipid-based nanocarriers. Additionally, this review discusses ongoing clinical trials and patents related to brain malignancy therapies and provides a glance into future perspectives for treating this condition.

Cardiac magnetic resonance findings in cardiac amyloidosis.

The purpose of this review is to highlight the increasing importance of cardiac magnetic resonance (CMR) imaging in diagnosing and managing cardiac amyloidosis, especially given the recent advancements in treatment options. This review emphasizes the crucial role of late gadolinium enhancement (LGE) with phase-sensitive inversion recovery (PSIR) techniques in both diagnosing and predicting patient outcomes in cardiac amyloidosis. The review also explores promising new techniques for diagnosing early-stage disease, such as native T1 mapping and ECV quantification. Additionally, it delves into experimental techniques like diffusion tensor imaging, MR elastography, and spectroscopy. This review underscores CMR as a powerful tool for diagnosing cardiac amyloidosis, assessing risk factors, and monitoring treatment response. While LGE imaging remains the current best practice for diagnosis, emerging techniques such as T1 mapping and ECV quantification offer promise for improved detection, particularly in early stages of the disease. This has significant implications for patient management as newer therapeutic options become available for cardiac amyloidosis.