Combined endoscopic mucosal resection and full-thickness resection for large colorectal polyps: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Combined endoscopic mucosal resection (EMR) with endoscopic Full thickness resection (EFTR) is an emerging technique that has been developed to target colorectal polyps larger than 2 cm. We performed a systematic review and meta-analysis to evaluate this technique for the resection of large colorectal lesions. METHODS: We conducted a comprehensive search of multiple electronic databases from inception through August 2023, to identify studies that reported on hybrid FTR. A random-effects model was employed to calculate the overall pooled technical success, macroscopic complete resection, free vertical margins resection rate, adverse events, and recurrence on follow up. RESULTS: A total of 8 Study arms with 244 patients (30% women) were included in the analysis. The pooled technical success rate was 97% (95% CI 88%-100%, I2 = 79.93%). The pooled rate of macroscopic complete resection was achieved in 95% (95% CI 90%-99%, I2 = 49.98) with a free vertical margins resection rate 88% (95% CI, 78%-96%, I2 = 63.32). The overall adverse events rate was 2% (95% CI 0%-5%, I2 = 11.64) and recurrence rate of 6% (95% CI 2%-12%, I2=20.32). CONCLUSION: Combined EMR with EFTR is effective and safe for resecting large, and complex colorectal adenomas, offering a good alternative for high surgical risk patients. Regional heterogeneity was observed, indicating that outcomes may be impacted by differences in operator expertise and industry training certification across regions. Comparative studies that directly compare combined EMR with EFTR against alternative methods such as ESD and surgical resection are needed.

Unlocking the genetic tapestry of autoimmune diseases: Unveiling common genes across multiple conditions.

OBJECTIVES: This study aimed to unravel the complexities of autoimmune diseases by conducting a comprehensive analysis of gene expression data across 10 conditions, including systemic lupus erythematosus (SLE), psoriasis, Sjögren's syndrome, sclerosis, immune-associated diseases, osteoarthritis, cystic fibrosis, inflammatory bowel disease (IBD), type 1 diabetes, and Guillain-Barré syndrome. METHODS: Gene expression profiles were rigorously examined to identify both upregulated and downregulated genes specific to each autoimmune disease. The study employed visual representation techniques such as heatmaps, volcano plots, and contour-MA plots to provide an intuitive understanding of the complex gene expression patterns in these conditions. RESULTS: Distinct gene expression profiles for each autoimmune condition were uncovered, with psoriasis and osteoarthritis standing out due to a multitude of both upregulated and downregulated genes, indicating intricate molecular interplays in these disorders. Notably, common upregulated and downregulated genes were identified across various autoimmune conditions, with genes like SELENBP1, MMP9, BNC1, and COL1A1 emerging as pivotal players. CONCLUSION: This research contributes valuable insights into the molecular signatures of autoimmune diseases, highlighting the unique gene expression patterns characterizing each condition. The identification of common genes shared among different autoimmune conditions, and their potential role in mitigating the risk of rare diseases in patients with more prevalent conditions, underscores the growing significance of genetics in healthcare and the promising future of personalized medicine.

Atrial arrhythmias following CAR-chimeric antigen receptor T-cell therapy: Incidence, risk factors and biomarker profile.

Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain.

Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential - A Review.

Fisetin is a bioactive compound found in numerous fruits and vegetables, including strawberries, apples, grapes, persimmon, cucumber, onion, etc. The compound is also wellknown for its neurotrophic, anti-inflammatory, anti-carcinogenic, anti-diabetic, and other healthpromoting properties. Although there is increasing agreement that it has therapeutic properties, its poor water solubility, high lipophilicity, and lower oral bioavailability make it difficult to use clinically. Extensive research has attempted to overcome these restrictions by developing novel, superior delivery systems. Considering the diverse potential, this review is the first to summarise the available data on Fisetin to collate the information related to analytical methods, pharmacological action, their mechanisms, regulatory aspects, and toxicity profile. It also covers the marketed products, their related clinical trials, and patent updates of the moiety. In addition, an endeavor has been attempted to discuss and assess the various drug delivery systems employed to increase the biological attributes of Fisetin. The presented manuscript is the first to present a compendium of up-to-date literature on all of the domains considered necessary for this type of natural molecule to carve down its path from being a mere dietary supplement to a promising therapeutic drug candidate. The manuscript will definitely benefit the researchers working on natural and bioactive compounds, industrial scientists, and the general population interested in Fesitin as a dietary supplement.

Hepatic Duct Adenoma Identified Using Direct Cholangioscopy.

Bile duct adenomas (BDAs) are rare benign tumors that can arise in the intra-hepatic or extra-hepatic biliary tree. We present a case of a 46-year-old female who presented with symptoms suggestive of choledocholithiasis. Direct cholangioscopy identified a 15 mm polypoid lesion in the common hepatic duct (CHD). Biopsy revealed a BDA. We present this case to highlight the role of direct cholangioscopy in the diagnosis and management of BDAs.

Recent Applications of Chitosan and Its Derivatives in Antibacterial, Anticancer, Wound Healing, and Tissue Engineering Fields.

Chitosan, a versatile biopolymer derived from chitin, has garnered significant attention in various biomedical applications due to its unique properties, such as biocompatibility, biodegradability, and mucoadhesiveness. This review provides an overview of the diverse applications of chitosan and its derivatives in the antibacterial, anticancer, wound healing, and tissue engineering fields. In antibacterial applications, chitosan exhibits potent antimicrobial properties by disrupting microbial membranes and DNA, making it a promising natural preservative and agent against bacterial infections. Its role in cancer therapy involves the development of chitosan-based nanocarriers for targeted drug delivery, enhancing therapeutic efficacy while minimising side effects. Chitosan also plays a crucial role in wound healing by promoting cell proliferation, angiogenesis, and regulating inflammatory responses. Additionally, chitosan serves as a multifunctional scaffold in tissue engineering, facilitating the regeneration of diverse tissues such as cartilage, bone, and neural tissue by promoting cell adhesion and proliferation. The extensive range of applications for chitosan in pharmaceutical and biomedical sciences is not only highlighted by the comprehensive scope of this review, but it also establishes it as a fundamental component for forthcoming research in biomedicine.

Trastuzumab-Induced Cardiotoxicity: When and How Much Should We Worry?

This review critically analyzes the incidence of trastuzumab-induced left ventricular systolic dysfunction and congestive heart failure (CHF), distinguishing between cases with and without prior anthracycline exposure. It highlights the fact that the elevated risk of trastuzumab-induced cardiotoxicity is closely associated with prior anthracycline exposure. In the absence of prior anthracycline exposure, the incidence rates of trastuzumab-induced cardiotoxicity, particularly CHF (ranging from 0% to 0.5%), are largely comparable with those reported in the general population, especially when reversibility is taken into account. Current cardiac surveillance recommendations during trastuzumab treatment have not yet adapted to the increasing adoption of nonanthracycline treatment strategies and the associated low risk of cardiotoxicity. We propose a refined monitoring protocol to reduce the frequency of cardiac evaluations for low-risk to moderate-risk patients, especially those receiving nonanthracycline treatments. By focusing on patients at high risk or those with prior anthracycline exposure, this strategy seeks to optimize the cost-effectiveness of cardiac care in oncology.

Cardiovascular toxicities associated with bispecific T-cell engager therapy.

BACKGROUND: Bispecific T-cell engagers (BTEs) are novel agents used to treat hematological malignancies. Early trials were underpowered to define cardiovascular adverse events (CVAE) and no large-scale studies systematically examined the CVAEs associated with BTEs. METHODS: Leveraging the US Food and Drug Administration's Adverse Event Reporting System-(FAERS), we identified the relative frequency of CVAEs after initiation of five BTE products approved by the Food and Drug Administration between 2014 and 2023 for the treatment of hematological malignancies. Adjusted reporting ORs (aROR) were used to identify disproportionate reporting of CVAEs with BTEs compared with background rates in the database. Fatality rates and risk ratios (RRs) for each adverse event (AE) were calculated. RESULTS: From 3668 BTE-related cases reported to FAERS, 747 (20.4%) involved CVAEs. BTEs as a class were associated with fatal CVAEs (aROR 1.29 (95% CI 1.12 to 1.50)), an association mainly driven by teclistamab (aROR 2.44 (95% CI 1.65 to 3.60)). Teclistamab was also associated with a disproportionate risk of myocarditis (aROR 25.70 (95% CI 9.54 to 69.23)) and shock (aROR 3.63 (95% CI 2.30 to 5.74)), whereas blinatumomab was associated with a disproportionate risk of disseminated intravascular coagulation (aROR 3.02 (95% CI 1.98 to 4.60)) and hypotension (aROR 1.59 (95% CI 1.25 to 2.03)). CVAEs were more fatal compared with non-CVAEs (31.1% vs 17.4%; RR 1.76 (95% CI 1.54 to 2.03)). Most CVAEs (83.3%) did not overlap with cytokine release syndrome. CONCLUSION: In the first postmarketing surveillance study of BTEs, CVAEs were involved in approximately one in five AE reports and carried a significant mortality risk.

Gender-Related Microaggressions in Orthopedic Surgery: A Comprehensive Survey of Women Orthopedists and Implications for Progress, Saudi Arabia.

Background: Microaggressions are subtle and often unintentional acts that can be verbal, nonverbal, or environmental, and they convey negative messages to individuals belonging to marginalized social groups. This study aims to determine the prevalence of microaggressions experienced by female Saudi orthopaedic surgeons. Methods: This cross-sectional study was conducted online and targeted female in orthopedic surgery across different regions of the Kingdom of Saudi Arabia. The survey was uploaded to Google Forms and distributed through social media platforms like Twitter, Instagram, and WhatsApp by well-trained data collectors. Results: In this survey we included 96 female Saudi orthopedics. Their mean age was 27.46 ± 12.20 years. Most respondents were either residents (52.63%), or specialists (23.16%). Most participants (92.63%) were still in training or early in their careers, with the vast majority (93.68%) had their residency in Saudi Arabia. Nearly three-fifths (61.05%) have reported experiencing microaggressions as victims, 76.84%, did not see themselves as perpetrators of microaggressions, 23.16% acknowledged having engaged in such behavior. Patients or their families were reported to be involved in microaggressions in 43.16% of cases, while male surgeons and male support staff were implicated at 51.58% and 23.16%, respectively. Additionally, other male medical doctors participate in microaggressions in 33.68% of instances. Female surgeons were identified as being involved in 22.11% of microaggressions, whereas 29.47% involve female support staff. Conclusion: The study's outcomes can help inform strategies to promote a supportive and inclusive environment within the field of orthopaedic surgery, encouraging positive interactions and equitable opportunities for all practitioners.

Totally endoscopic, robotic-assisted tricuspid valve repair and biatrial CryoMAZE.

We describe in detail our technique for totally endoscopic, robotic-assisted tricuspid valve repair for iatrogenic tricuspid regurgitation and biatrial cryoMAZE.

Engineered liposomes mediated approach for targeted colorectal cancer drug Delivery: A review.

Colorectal cancer (CRC) continues to be one of the most prevalent and deadliest forms of cancer worldwide, despite notable advancements in its management. The prognosis for metastatic CRC remains discouraging, with a relative 5-year survival rate for stage IV CRC patients. Conventional treatments for advanced malignancies such as chemotherapy, often face limitations in effectively targeting cancer cells resulting in off-target distribution and significant side effects. In the quest for better strategies, researchers have explored numerous alternatives. Among these, nanoparticles (NPs) specifically liposomes have emerged as one of the most promising candidates in developing targeted delivery systems for cancer therapeutics. This review discusses the current approaches employing functionalised liposomes to overcome major biological barriers in therapeutics delivery for CRC treatment. We have also shared our perspectives on the technological development of liposomes for future clinical use and highlighted a few useful insights on the material choices for future research work in CRC.

Microbubbles: Revolutionizing Biomedical Applications with Tailored Therapeutic Precision.

BACKGROUND: Over the past ten years, tremendous progress has been made in microbubble-based research for a variety of biological applications. Microbubbles emerged as a compelling and dynamic tool in modern drug delivery systems. They are employed to deliver drugs or genes to targeted regions of interest, and then ultrasound is used to burst the microbubbles, causing site-specific delivery of the bioactive materials. OBJECTIVE: The objective of this article is to review the microbubble compositions and physiochemical characteristics in relation to the development of innovative biomedical applications, with a focus on molecular imaging and targeted drug/gene delivery. METHODS: The microbubbles are prepared by using various methods, which include cross-linking polymerization, emulsion solvent evaporation, atomization, and reconstitution. In cross-linking polymerization, a fine foam of the polymer is formed, which serves as a bubble coating agent and colloidal stabilizer, resulting from the vigorous stirring of a polymeric solution. In the case of emulsion solvent evaporation, there are two solutions utilized in the production of microbubbles. In atomization and reconstitution, porous spheres are created by atomising a surfactant solution into a hot gas. They are encapsulated in primary modifier gas. After the addition of the second gas or gas osmotic agent, the package is placed into a vial and sealed after reconstituting with sterile saline solution. RESULTS: Microbubble-based drug delivery is an innovative approach in the field of drug delivery that utilizes microbubbles, which are tiny gas-filled bubbles, act as carriers for therapeutic agents. These microbubbles can be loaded with drugs, imaging agents, or genes and then guided to specific target sites. CONCLUSION: The potential utility of microbubbles in biomedical applications is continually growing as novel formulations and methods. The versatility of microbubbles allows for customization, tailoring the delivery system to various medical applications, including cancer therapy, cardiovascular treatments, and gene therapy.

Quercetin as a Therapeutic Product: Evaluation of Its Pharmacological Action and Clinical Applications-A Review.

Quercetin is the major polyphenolic flavonoid that belongs to the class called flavanols. It is found in many foods, such as green tea, cranberry, apple, onions, asparagus, radish leaves, buckwheat, blueberry, broccoli, and coriander. It occurs in many different forms, but the most abundant quercetin derivatives are glycosides and ethers, namely, Quercetin 3-O-glycoside, Quercetin 3-sulfate, Quercetin 3-glucuronide, and Quercetin 3'-metylether. Quercetin has antioxidant, anti-inflammatory, cardioprotective, antiviral, and antibacterial effects. It is found to be beneficial against cardiovascular diseases, cancer, diabetes, neuro-degenerative diseases, allergy asthma, peptic ulcers, osteoporosis, arthritis, and eye disorders. In pre-clinical and clinical investigations, its impacts on various signaling pathways and molecular targets have demonstrated favorable benefits for the activities mentioned above, and some global clinical trials have been conducted to validate its therapeutic profile. It is also utilized as a nutraceutical due to its pharmacological properties. Although quercetin has several pharmacological benefits, its clinical use is restricted due to its poor water solubility, substantial first-pass metabolism, and consequent low bioavailability. To circumvent this limited bioavailability, a quercetin-based nanoformulation has been considered in recent times as it manifests increased quercetin uptake by the epithelial system and enhances the delivery of quercetin to the target site. This review mainly focuses on pharmacological action, clinical trials, patents, marketed products, and approaches to improving the bioavailability of quercetin with the use of a nanoformulation.

Positive regulation of oxidative phosphorylation by nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice.

Metabolic reprogramming is one of the hallmarks of tumorigenesis. Here, we show that nuclear myosin 1 (NM1) serves as a key regulator of cellular metabolism. NM1 directly affects mitochondrial oxidative phosphorylation (OXPHOS) by regulating mitochondrial transcription factors TFAM and PGC1α, and its deletion leads to underdeveloped mitochondria inner cristae and mitochondrial redistribution within the cell. These changes are associated with reduced OXPHOS gene expression, decreased mitochondrial DNA copy number, and deregulated mitochondrial dynamics, which lead to metabolic reprogramming of NM1 KO cells from OXPHOS to aerobic glycolysis.This, in turn, is associated with a metabolomic profile typical for cancer cells, namely increased amino acid-, fatty acid-, and sugar metabolism, and increased glucose uptake, lactate production, and intracellular acidity. NM1 KO cells form solid tumors in a mouse model, suggesting that the metabolic switch towards aerobic glycolysis provides a sufficient carcinogenic signal. We suggest that NM1 plays a role as a tumor suppressor and that NM1 depletion may contribute to the Warburg effect at the onset of tumorigenesis.

Awareness of Chronic Obstructive Pulmonary Disease and Its Risk Factors Among the Adult Population of the Qassim Region, Saudi Arabia.

BACKGROUND: Epidemiological studies are crucial in appraising the occurrence of chronic obstructive pulmonary disease (COPD) in a specific region, establishing benchmarks, and devising effective preventive measures. It is against this background that the study aims to evaluate adult awareness of COPD and its risk factors among adults in the Qassim Region, Saudi Arabia. METHOD: This observational cross-sectional study was conducted in the Qassim Region and involved consenting adults who voluntarily participated. Between 20 May and 4 June 2023, a self-administered online survey was distributed through social media platforms, utilizing an anonymous, self-explanatory questionnaire to evaluate participants' awareness of COPD. RESULTS: In our study, a total of 1,306 participants were enrolled, of which 27.6% (n=360) reported having ever heard of COPD. Among all respondents, 21.3% (n=278) stated that they study or work in medical-related fields, and out of them, 60.4% (n=168) had prior awareness of COPD. Upon excluding participants associated with medical-related fields, the overall awareness level decreased to 18.7%. The majority of respondents fell within the age range of 18 to 29 years, of whom 34.5% had ever heard of COPD. Regarding smoking habits, the majority were cigarette smokers (38.4%), and of all cigarette smokers, 22.4% had heard of COPD. The second highest proportion of smokers (35.8%) were electronic smokers, and among them, 24.1% were aware of COPD. The lowest proportion of smokers (25.8%) were shisha smokers, with 25.6% of them having heard of COPD. Among the 1,306 respondents, only 27.5% (n=360) had ever heard of COPD. When asked about the organ affected by COPD, 81% (n=292) of those who were aware of the condition correctly responded that it affects the lungs. On the other hand, 8.9% (n=32) incorrectly selected "heart" as the affected organ, while 2.5% (n=9) chose "I don't know," and none selected "throat." CONCLUSION: The Qassim Region in Saudi Arabia exhibits a reduced level of COPD awareness among the general population. It is imperative to urgently address this situation and enhance awareness for improved COPD diagnosis and treatment. Considering the region's high prevalence of COPD and associated risk factors, it becomes vital to strengthen educational curricula and integrate COPD awareness into public forums and awareness campaigns. Moreover, conducting additional national research would be instrumental in assisting policymakers in developing effective preventive and therapeutic strategies.

Factors Related to Relapse of Congenital Talipes Equinovarus (CTEV) After the Ponseti Method.

BACKGROUND: Congenital talipes equinovarus (CTEV) is one of the common congenital disorders in pediatric orthopedic practice that affects a large group of children.It is a combination of four parts of deformity that affect either a single foot or both feet. Our aim in this study is to estimate the prevalence and incidence of CTEV and to evaluate the risk factors that lead to relapse in some children to avoid relapse in future and complex surgical interventions, as well as to improve the final outcome. MATERIALS AND METHODS: A retrospective cohort study for the cases of CTEV was conducted to estimate the prevalence of relapse in children with CTEV after management by the Ponseti method and to evaluate the risk factors that lead to recurrence. RESULT: The study includes 103 patients with CTEV, and only 22 patients had relapse. The prevalence rate of relapsed cases was 20.4%, and the incidence was 42 per thousand. The average number of casts applied was 4.05 ± 1.37. The average severity of the deformity that was measured by the Pirani score was 4.97 ± 1.21. The most common atypical presentation of CTEV was associated with developmental dysplasia of the hip (DDH), followed by myelomeningocele (MMC). CONCLUSION: The only significant factors in the study were the Pirani score and non-compliance of the brace with p < 0.05. There was not any significance in the correction of the deformity by Ponseti between idiopathic and non-idiopathic CTEV based on the number of casts and the Pirani score. The dynamic foot brace can be the solution for the high recurrence rate, yet more studies are needed in the future.

Atorvastatin for Anthracycline-Associated Cardiac Dysfunction: The STOP-CA Randomized Clinical Trial.

Importance: Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use. Objective: To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction. Design, Setting, and Participants: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022. Interventions: Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months. Results: Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups. Conclusions and Relevance: Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use. Trial Registration: ClinicalTrials.gov Identifier: NCT02943590.