Therapeutic Options Research Articles

Patient Blood Management Program Implementation: Comprehensive Recommendations and Practical Strategies.

Blood transfusion is one of the most common medical practices worldwide. However, current scientific literature has shown that the immunomodulatory effects of blood transfusion are associated with an increased likelihood of infection, prolonged hospitalization, and morbimortality. Also, it means high costs for healthcare systems. In this context, acknowledging that blood transfusions are essentially heterologous cell transplantations, the use of therapeutic options has gained strength and is collectively known as the patient blood management (PBM) program. PBM is an approach based on three main pillars: (1) treating anemias and coagulopathies in an optimized manner, especially in the preoperative period; (2) optimizing perioperative hemostasis and the use of blood recovery systems to avoid the loss of the patient's blood; (3) anemia tolerance, with improved oxygen delivery and reduced oxygen demand, particularly in the postoperative period. Current scientific evidence supports the effectiveness of PBM by reducing the need for blood transfusions, decreasing associated complications, and promoting more efficient and safer blood management. Thus, PBM not only improves clinical outcomes for patients but also contributes to the economic sustainability of healthcare systems. The aim of this review was to summarize PBM strategies in a comprehensive, evidence-based approach through a systematic and structured model for PBM implementation in tertiary hospitals. The recommendations proposed herein are from researchers and experts of a high-complexity university hospital in the network of the Sistema Único de Saúde, presenting itself as a strategy that can be followed as a guideline for PBM implementation in other settings.

Efficacy and Safety of Pemafibrate, a Novel Selective PPARα Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial.

Pemafibrate substantially lowers serum triglyceride (TG) levels and increases high-density lipoprotein cholesterol (HDL-C) levels primarily in Japan, but it has not been evaluated in China. We aimed to confirm the efficacy and safety of pemafibrate in Chinese patients with hypertriglyceridemia and low HDL-C levels by comparing placebo and fenofibrate. A multicenter, double-masked trial was conducted in China involving 344 patients with high TG and low HDL-C levels randomly assigned to one of four groups: pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, or placebo for 12 weeks. The primary endpoint was the percentage change in fasting TG levels. The percentage change in TG levels from baseline was -34.1%, -44.0%, -30.5%, and 6.5% in the pemafibrate 0.2 mg/d, pemafibrate 0.4 mg/d, fenofibrate 200 mg/d, and placebo groups, respectively. Pemafibrate 0.4 mg/d significantly reduced TG levels compared with that in both placebo (p＜0.0001) and fenofibrate groups (p=0.0083). Significant improvements in HDL-C, remnant cholesterol, and apolipoprotein A1 levels were also observed with both doses of pemafibrate than with the placebo. Pemafibrate showed significantly smaller changes in alanine aminotransferase, aspartate aminotransferase, and serum creatinine levels than those with fenofibrate. In Chinese patients, pemafibrate exhibited superior efficacy in improving TG levels and enhanced hepatic and renal safety compared to fenofibrate. Thus, pemafibrate may represent a promising therapeutic option for dyslipidemia in Chinese patients.

Metabolic Associated Fatty Liver Disease in Children and Adolescents: Mechanisms of a Silent Epidemic and Therapeutic Options.

Non-alcoholic fatty liver disease (NAFLD) is now identified as a hepatic sign of metabolic syndrome and is the most frequent cause of chronic liver disease in all ages. It is assumed that a genetic predisposition associated with epigenetic factors participates in the evolution of this condition. Visceral obesity and insulin resistance (IR) have always been considered the most important causative factors of Metabolic Syndrome (MetS) and NAFLD, but currently, the interaction between genetic heritage and environmental factors is increasingly considered fundamental in the genesis of metabolic disorders associated with NAFLD. In fact, in patients with NAFLD, insulin resistance, arterial hypertension, abdominal obesity, dyslipidemia and reduced intestinal permeability have often been found, as well as a higher prevalence of coronary artery disease, obstructive sleep apnea, polycystic ovary syndrome and osteopenia, which define a MetS framework. Early diagnosis is needed to prevent disease progression through primarily lifestyle interventions. Unfortunately, at present, there are no molecules recommended for pediatric patients. However, several new drugs are in clinical trials. For this reason, targeted studies on the interaction between genetics and environmental factors involved in the development of NAFLD and MetS and on the pathogenetic mechanisms that determine the evolution in non-alcoholic steatohepatitis (NASH), should be implemented. Therefore, it is desirable that future studies may be useful in identifying patients at risk of developing NAFLD and MetS early.

Resveratrol: Targeting Cancer Stem Cells and ncRNAs to Overcome Cancer Drug Resistance.

A major challenge in treating cancer is the development of drug resistance, which can result in treatment failure and tumor recurrence. Targeting cancer stem cells (CSCs) and non-coding RNAs (ncRNAs) with a polyphenolic substance called resveratrol has the ability to combat this problem by lowering cancer resistance to drugs and opening up new therapeutic options. Resveratrol alters the expression of genes related to self-renewal, modulating important signaling pathways involved in cancer initiation and CSC control. Additionally, resveratrol affects non-coding RNAs (ncRNAs), including Micro-RNAs (miRNAs) and long non-coding RNAs (lncRNAs which are essential for stemness, drug resistance, and other cancer-related activities. Numerous studies have shown that resveratrol has the potential to be an effective anticancer drug when used in combination therapy, but issues with absorption and pharmacokinetics still need to be resolved before it can be used in clinical applications. Reducing chemotherapy resistance by better understanding the intricate mechanisms by which resveratrol affects cancer cells and CSCs, as well as its impact on ncRNA expression, could eventually contribute to more effective cancer treatments. To completely understand these pathways and optimize the utilization of resveratrol in combination treatments, additional study is necessary.

Hereditary angioedema: current therapeutic management and future approaches.

The aim of this review is to provide an account of the focus of therapeutic strategies for hereditary angioedema (HAE), give a brief overview of those used in the past and set aside and toughly discuss those currently available as first line. Further research is ongoing and the future therapeutic approaches that are still in different phases of study will be reviewed as well. In the last two decades, major research advancements on HAE pathophysiology and management were made and numerous novel therapeutic options are now available. Compared to the past, drugs available nowadays are more effective, well tolerated, and possibly have a more convenient administration route. Moreover, numerous other drugs with innovative mechanisms of action are under development. HAE is a rare genetic disease that if not promptly treated, it can lead to death from asphyxiation. Furthermore, due to its disfiguring and painful manifestations, HAE implies an important burden on the quality of life. Recently, following great research progresses on HAE therapy, evidence-based guidelines on HAE management were released. The therapeutic landscape of HAE is still under florid development, and it is possible novel treatments will remarkably revolutionize HAE management in the future.

Pre-clinical Aspects and Contemporary Treatments of Parkinson's Disease.

After Alzheimer's disease, the second slot for the most common neurodegenerative disease, is occupied by Parkinson's disease. The symptoms of Parkinson's are classified as motor symptoms and non-motor symptoms. Motor symptoms involve rigidity, tremors, bradykinesia, and postural instability. Non-motor symptoms consist of cognitive dysfunction, salivation, lacrimation, etc. Objectives: The objectives of this study are to find out the most recent treatment options for Parkinson's disease. Research and review papers are collected from different databases like Google Scholar, PubMed, Mendeley, Scopus, Science Open, and the Directory of Open Access Journals using different keywords such as "Parkinson's disease, biomarkers, animal models". Currently, various novel therapeutics have been emerging for PD. These may include treatments that may control the symptoms without causing any other severe side effects with already available treatments. Better therapies such as gene therapies, cell-based treatments, and regenerative therapies, which may evolve over time, can be a better therapeutic option. There is a need for the development of novel and potential therapeutic strategies that offer fewer side effects to patients. Several clinical, biochemical, and imaging markers that are noteworthy in Parkinson's disease examination have been discussed here. Current work in the field of Parkinson's disease has developed a variety of significant small animal models, such as viral vector models and seeding models, including the insertion of preformed fibrils of alpha-synuclein. The brief concepts regarding risk factors, pathogenesis, clinical diagnosis, and emerging treatments of PD are discussed in this review article.

Conversion Therapy for Gastric Cancer with Peritoneal Metastasis

Peritoneal metastasis in gastric cancer has a poor prognosis and is increasing in prevalence. Neoadjuvant chemotherapy is used for advanced tumors; however, surgery is generally not considered for metastatic and unresectable diseases. Recently, conversion surgery, a treatment which aims for an R0 resection following chemotherapy, has become a novel therapeutic option with better survival rates. In addition to surgery, hyperthermic intraperitoneal chemotherapy (HIPEC) leads to significant tumor reduction, but it is limited by its morbidity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) delivers high concentrations of chemotherapy, but does not remove the tumor, making it useful mostly in palliative settings. Intraperitoneal (IP) therapy, known for its minimally invasive nature and repeatability, shows promise but requires further research. Ultimately, an integrated approach involving systemic chemotherapy, radical gastrectomy, HIPEC, PIPAC and IP chemotherapy can be used to optimize treatment outcomes of gastric cancer patients with peritoneal metastasis.

GWAS Identifies DPP6 as Risk Gene of Cognitive Decline in Parkinson's Disease.

Cognitive decline is among the most common non-motor symptoms in Parkinson's disease (PD), while its physiological mechanisms remain poorly understood. Genetic factors constituted a fundamental determinant in the heterogeneity of cognitive decline among PD patients. However, the underlying genetic background was still less studied. To explore the genetic determinants contributing to cognitive decline in PD, we performed genome-wide survival analysis using a Cox proportional hazards model in a longitudinal cohort of 450 Chinese patients with PD, and further explored the functional effect of the target variant. Additionally, we built a clinical-genetic model by incorporating clinical characteristics and polygenic risk score (PRS) to predict cognitive decline in PD. The cohort was followed up for an average of 5.25 (SE = 2.46) years, with 95 incidents of cognitive impairment. We identified significant association between locus rs75819919 (DPP6) and accelerated cognitive decline (p = 8.63E-09, beta = 1.74, SE = 0.30). Dual-luciferase reporter assay suggested this locus might be involved in the regulation of DPP6 expression. Using data set from the UK Biobank, we identified rs75819919 was associated with cognitive performance in the general population. Incorporation of PRS increased the model's predictability, achieving an average AUC of 75.6% through fivefold cross-validation in 1000 iterations. These findings improve the current understanding of the genetic etiology of cognitive impairment in PD, and provide a novel target DPP6 to explore therapeutic options. Our results also demonstrate the potential to develop clinical-genetic model to identify patients susceptible to cognitive impairment and thus provide personalized clinical guidance.

Hepatitis C: From diagnosis to global virus elimination

Chronic infection with hepatitis C virus (HCV) is a common cause of complications such as liver cirrhosis and hepatocellular carcinoma (HCC). It is one of the most significant infectious diseases worldwide, posing a substantial health burden. Since the introduction of direct-acting antiviral agents (DAAs), the treatment landscape has undergone a revolution. HCV infection is curable, and the treatment is safe and well tolerated. Due to the availability of this effective therapeutic option, the World Health Organization (WHO) set an ambitious goal in 2015 to eliminate Hepatitis C by 2030, a goal that the German government also embraced in 2016. The key tasks involve identifying previously undiagnosed cases and ensuring they receive antiviral treatment. Addressing at-risk populations through specific measures, including micro-elimination projects and population-wide campaigns, is essential to achieving the WHO's target both in Germany and globally.

Radiofrequency ablation via catheter and transpapillary access in patients with cholangiocarcinoma (ACTICCA-2 trial) – a multicenter, randomized, controlled, open-label investigator-initiated trial

BackgroundDespite the recent advances in cancer treatment, the therapeutic options for patients with biliary tract cancer are still very limited and the prognosis very poor. More than 50% of newly diagnosed patients with biliary tract cancer are not amenable to curative surgical treatment and thus treated with palliative systemic treatment. Malignant bile duct obstructions in patients with perihilar and/or ductal cholangiocarcinoma (CCA) represents one of the most important challenges in the management of these patients, owning to the risk represented by developing life-threatening cholangitis which, in turn, limits the use of systemic treatment. For this reason, endoscopic stenting and/or bile duct decompression is the mainstay of treatment of these patients. Data on efficacy and safety of adding radiofrequency ablation (RFA) to biliary stenting is not conclusive. The aim of this multicenter, randomized trial is to evaluate the effect of intraductal RFA prior to bile duct stenting in patients with unresectable perihilar or ductal CCA undergoing palliative systemic therapy.Methods/DesignACTICCA-2 is a multicenter, randomized, controlled, open-label, investigator-initiated trial. 120 patients with perihilar or ductal CCA with indication for biliary stenting and systemic therapy will be randomized 1:1 to receive either RFA plus bile duct stenting (interventional arm) or bile duct stenting alone (control arm). Patients will be stratified by trial site and tumor location (perihilar vs. ductal). Both arms receive palliative systemic treatment according to the local standard of care determined by a multidisciplinary tumorboard. The primary endpoint is time to first biliary event, which is determined by an increase of bilirubin to > 5 mg/dl and/or the occurrence of cholangitis leading to premature stent replacement and/or disruption of chemotherapy. Secondary endpoints include overall survival, safety according to NCI CTCAE v5, quality of life assessed by questionnaires (EORTC QLQ-C30 and QLQ-BIL21), clinical event rate at 6 months after RFA and total days of over-night stays in hospital. Follow-up for the primary endpoint will be 6 months, while survival assessment will be continued until end of study (maximum follow-up 30 month). All patients who are randomized and who underwent endoscopic stenting will be used for the primary endpoint analysis which will be conducted using a cause-specific Cox proportional hazards model with a frailty for trial site and fixed effects for the treatment group, tumor location, and stent material.DiscussionACTICCA-2 is a multicenter, randomized, controlled trial to assess efficacy and safety of adding biliary RFA to bile duct stenting in patients with CCA receiving palliative systemic treatment.Trial registrationThe study is registered with ClinicalTrials.gov (NCT06175845) and approved by the local ethics committee in Hamburg, Germany (2024-101232-BO-ff). This manuscript reflects protocol version 1 as of January 9th, 2024.Graphical

Efficacy and Safety of BoozLiv™ as an add on therapy in patients with alcoholic liver disease: An open-label, randomized controlled trial

BackgroundAlcoholic Liver Disease (ALD) poses a significant global health threat, contributing to millions of deaths each year. Despite the well-established link between chronic alcohol consumption and liver damage, treatment options remain limited, emphasizing the need for innovative approaches. MethodsAn open-label, randomized controlled trial was conducted in India, involving 68 adult ALD patients over a 12-week period. The patients were randomized into two groups: one receiving standard therapy and the other receiving standard therapy along with BoozLiv™ syrup. Liver function tests, Model for End-Stage Liver Disease (MELD) scores, and safety parameters were assessed at various intervals. ResultsThe study demonstrated that BoozLiv™ syrup, as an add-on therapy, significantly reduced total bilirubin, direct bilirubin, SGOT, SGPT, ALP, and GGT levels compared to standard therapy alone (p<0.05). The MELD score, indicative of liver function, showed a substantial improvement in the BoozLiv™ group (p<0.01). Safety analysis revealed that BoozLiv™ was well-tolerated, with only minor adverse effects such as nausea and vomiting reported. ConclusionBoozLiv™ syrup, used in conjunction with standard therapy, showed promising results in improving liver function and reducing liver damage markers in ALD patients. The safety profile was favorable and no patient has withdrawn their consent due to adverse events. Further long-term studies in larger populations are warranted to validate these findings and establish BoozLiv™ as a potential therapeutic option for ALD.

Onasemnogene abeparvovec gene therapy for spinal muscular atrophy: A cohort study from the United Arab Emirates.

Spinal muscular atrophy (SMA) manifests with progressive motor neuron degeneration, leading to muscle weakness. Onasemnogene abeparvovec is a US Food and Drug Administration-approved gene replacement therapy for SMA. This study aimed to present short-term data of children in the United Arab Emirates (UAE) treated with onasemnogene abeparvovec, particularly in the context of children requiring invasive ventilatory support via tracheostomy. A retrospective analysis was performed on 60 children who received onasemnogene abeparvovec. All these children received corticosteroids. They were followed up for up to 3 months. Motor function assessments were performed before and after the gene therapy. Comprehensive clinical evaluations, including pulmonary functions, were performed at baseline and the 3-month mark. Forty-three percent were male, and the mean age at the time of infusion was 29.6 months (SD ± 17.2). The mean weight was 10.1 kg (SD 2.6). All children demonstrated marked improvements in motor function within 3 months of gene therapy administration. No adverse effects attributable to corticosteroid therapy were observed. Positive clinical outcomes, including increased ventilator-free intervals, reduced antibiotic dependency, and fewer hospital admissions, were reported among children with invasive ventilation via tracheostomy. This study demonstrates the favorable tolerability and promising responses to onasemnogene abeparvovec in invasively ventilated pediatric patients. Early improvements in motor function, as observed within 3 months post-treatment, suggest its potential as a viable therapeutic option for this vulnerable patient population.

Anti-inflammatory effects and related mechanisms of naringenin in human periodontal ligament stem cells under lipopolysaccharide stimulation based on RNA sequencing.

RNA sequencing (RNA-seq) and bioinformatic analysis were combined and used to explore the anti-inflammatory effects and mechanisms of naringenin (Nar) in lipopolysaccharide (LPS)-stimulated human periodontal ligament stem cells (hPDLSCs). Cell counting kit-8, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA) were adopted to detect the effects of Nar on the proliferation and expression of inflammatory factors in LPS-stimulated hPDLSCs, screening for the optimal anti-inflammatory concentration of Nar. Differentially expressed genes (DEGs) were screened using |log2FC|≥1 and P≤0.05 as criteria. Volcano plot analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the String database, and the MCODE module of Cytoscape were utilized to select core genes and enriched pathways. The effects on the nuclear factor κB (NF-κB) signaling pathway were verified using ELISA, qRT-PCR, and Western blot. Appropriate concentrations of Nar could alleviate the expression of inflammatory factors and promote the proliferation of hPDLSCs stimulated by LPS. The best anti-inflammatory effect was achieved with 20 μmol/L Nar. RNA-seq showed significant enrichment of inflammation-related signaling pathways. The anti-inflammatory effect of Nar was mediated by inhibiting the NF-κB signaling pathway, similar to the effect of the NF-κB inhibitor BAY 11-7802. Nar could exert its anti-inflammatory effects by inhibiting the NF-κB signaling pathway, making it a potential therapeutic option for the adjuvant treatment of periodontitis.

TSHR-IGF-IR complex drives orbital fibroblast misbehavior in thyroid eye disease.

Evolving understanding of thyroid eye disease (TED) has led to rapidly advancing therapeutic options. Most new treatments under development or recently available to patients are predicated on insights into disease mechanism. TED, a disfiguring process, involves inflammation and remodeling of the connective tissues around the eye. TED most frequently presents as a component of Graves' disease. Advances in our understanding of cells involved in TED and their molecular interactions have led to novel therapeutic targets. Among these cell types are orbital fibroblasts and a subset comprising monocyte progenitor cells, known as CD34+CXCR4+ fibrocytes. Among the attributes of fibrocytes is their expression of several autoantigens associated with Graves' disease, including TSHR, thyroglobulin and thyroperoxidase. Fibrocytes also express high levels of the insulin-like growth factor-I (IGF-I) receptor, thought to mediate fibroblast activation. Therapeutically targeting the TSHR/IGF-IR receptor complex using an IGF-I receptor antagonist, teprotumumab, has resulted in substantial clinical benefit for patients with TED. The neural axon repellent, Slit2, and its cognate receptor, ROBO1, appear to modulate the inflammatory phenotype of these orbit-infiltrating fibrocytes. More detailed understanding of orbital fibroblasts and the distinctions between cell subsets comprising them should lead to more effective therapies with fewer side effects.

Therapeutic potential of oral alginate nanoparticles against experimental toxoplasmosis

Side effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.

Cucurbitacin I exerts its anticancer effects by inducing cell cycle arrest via the KAT2A-UBE2C/E2F1 pathway and inhibiting HepG2-induced macrophage M2 polarization

Hepatocellular carcinoma (HCC) is one of the most common malignancies globally, particularly prevalent in China, where it accounts for nearly half of the world's new cases and deaths each year, but has limited therapeutic options. This study systematically investigated the impact of cucurbitacin I on HCC cell lines including SK-Hep-1, Huh-7, and HepG2. The results revealed that cucurbitacin I not only inhibited cell proliferation, cell migration and colony formation, but also induced apoptosis in HCC cells. The apoptotic induction was accompanied by a decrease in the expression of the anti-apoptotic factor B-cell lymphoma 2 (Bcl2), and an elevation in the expression levels of pro-apoptotic factors, including tumor protein p53 (P53), bcl2 associated X-apoptosis regulator (Bax), and caspase3 (Cas3). Additionally, cucurbitacin I caused cell cycle arrest by modulating the lysine acetyltransferase 2A (KAT2A)-E2F transcription factor 1 (E2F1)/Ubiquitin-conjugating enzyme E2 C (UBE2C) signaling axis. In terms of regulation on tumor microenvironment, cucurbitacin I was demonstrated the ability to inhibit HCC cell-induced M2 polarization of macrophages. This comprehensive study unveils the multifaceted anti-cancer mechanisms of cucurbitacin I, providing robust support for its potential application in the treatment of HCC, offering new avenues for the future development of HCC treatment strategies.

Comprehensive molecular characterization of TFE3-rearranged renal cell carcinoma.

TFE3-rearranged renal cell cancer (tRCC) is a rare form of RCC that involves chromosomal translocation of the Xp11.2 TFE3 gene. Despite its early onset and poor prognosis, the molecular mechanisms of the pathogenesis of tRCC remain elusive. This study aimed to identify novel therapeutic targets for patients with primary and recurrent tRCC. We collected 19 TFE3-positive RCC tissues that were diagnosed by immunohistochemistry and subjected them to genetic characterization to examine their genomic and transcriptomic features. Tumor-specific signatures were extracted using whole exome sequencing (WES) and RNA sequencing (RNA-seq) data, and the functional consequences were analyzed in a cell line with TFE3 translocation. Both a low burden of somatic single nucleotide variants (SNVs) and a positive correlation between the number of somatic variants and age of onset were observed. Transcriptome analysis revealed that four samples (21.1%) lacked the expected fusion event and clustered with the genomic profiles of clear cell RCC (ccRCC) tissues. The fusion event also demonstrated an enrichment of upregulated genes associated with mitochondrial respiration compared with ccRCC expression profiles. Comparison of the RNA expression profile with the TFE3 ChIP-seq pattern data indicated that PPARGC1A is a metabolic regulator of the oncogenic process. Cell proliferation was reduced when PPARGC1A and its related metabolic pathways were repressed by its inhibitor SR-18292. In conclusion, we demonstrate that PPARGC1A-mediated mitochondrial respiration can be considered a potential therapeutic target in tRCC. This study identifies an uncharacterized genetic profile of an RCC subtype with unique clinical features and provides therapeutic options specific to tRCC.

Real-life Effectiveness and Safety of Guselkumab in Moderate-to-Severe Plaque Psoriasis: A 104-Week Retrospective Single-Center Study.

Guselkumab is a monoclonal antibody approved for treating moderate-to-severe plaque psoriasis. Long-term data on the effectiveness and safety of guselkumab in a real-world setting are still limited. We conducted a 104-week monocentric retrospective study on 102 psoriasis patients, all treated with guselkumab for at least 16 weeks. At each visit, we used the Psoriasis Area and Severity Index (PASI): effectiveness endpoints were the percentages of patients achieving 75%/90%/100% (PASI 75/90/100) improvement in PASI compared with baseline. The Kaplan-Meier curve was used to assess the drug survival. At week 16, PASI 90 and PASI 100 were achieved by 49.02% and 32.35% of patients. At week 52, PASI 90 and PASI 100 were achieved by 71.58% and 55.79% of patients. After 2 years, PASI 90 and PASI 100 were achieved by 79.63% and 61.11% of patients. Obese and overweight patients had comparable PASI 90 and PASI 100 responses throughout the study. At week 104, no significant differences were observed between bio-na&iuml;ve and bio-experienced patients regarding all effectiveness endpoints. No significant safety signals were reported in our study. After 24 months, 91.57% of our cohort was still on treatment with guselkumab. Our findings, although limited by the study's retrospective nature, confirm that guselkumab is a safe and effective therapeutic option for a "real-life" cohort of patients with psoriasis. J Drugs Dermatol. 2024;23(8):632-639.&nbsp; doi:10.36849/JDD.7486R1.

Potential kidney protective effects of glucagon-like peptide-1 receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes (T2DM) with chronic kidney disease (CKD). This class of medication has demonstrated promising results in reducing albuminuria, preserving estimated glomerular filtration rate (eGFR), and mitigating cardiovascular (CV) risk, making them potential therapeutic options for individuals with CKD. The kidney protective effects of GLP-1RAs extend beyond glycaemic control, and are thought to be attributed to their anti-inflammatory, antioxidant, and natriuretic properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure, or reduce CV and kidney related death in people with T2DM and CKD. The Research Study to See How Semaglutide (a once weekly subcutaneous administered GLP-1RA) Works Compared to Placebo in People with Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) was recently stopped because of efficacy. The primary end point for the FLOW trial consists of a composite endpoint of (i) onset of chronic kidney failure; (ii) death from kidney failure; (iii) cardiovascular death; and (iv) onset of a persistent ≥50% reduction in eGFR from baseline. It has also been reported by the sponsors of the trial that the primary end point of the trial was reduced by 24% with both CKD and CV outcomes contributing to risk reduction. In anticipation of the results of the FLOW trial being published, we review the current evidence surrounding kidney outcomes and proposed kidney protective pathways associated with GLP-1RA use.

Review of Current Clinical Options for the Management of Behavioral and Psychological Symptoms of Dementia.

Dementia is a disease most prevalent in the older adult population. The cognitive symptoms of dementia include impairments in problem-solving, memory, and language. Some patients experience noncognitive symptoms in addition to the cognitive symptoms of dementia. These noncognitive symptoms are called behavioral and psychological symptoms of dementia or BPSD. The primary objective of our study was to examine the therapeutic options, guidelines, and clinical considerations for the management of BPSD. The existing literature about BPSD was reviewed with searches in PubMed, MEDLINE, and online search platforms. Dysregulation of neurotransmission involving acetylcholine, dopamine, and serotonin has been shown to cause behavioral and psychological symptoms of Alzheimer's disease. BPSD can include hallucinations, agitation, delusions, anxiety, apathy, abnormal body movements, irritability, depression, disinhibition, and sleep or appetite changes. Pharmacologic therapies used in the treatment of BPSD include antidepressants, antipsychotics, anxiolytics, and anticonvulsants. Treatment can be tailored to the specific noncognitive symptoms that are experienced. The use of these agents may be limited based on recommendations from the Beers Criteria®, STOPP criteria, treatment guidelines, and FDA warnings.