Recent Advances in RNA Interference-Based Therapy for Hepatocellular Carcinoma: Emphasis on siRNA.

Even though RNA treatments were first proposed as a way to change aberrant signaling in cancer, research in this field is currently ongoing. The term "RNAi" refers to the use of several RNAi technologies, including ribozymes, riboswitches, Aptamers, small interfering RNA (siRNA), antisense oligonucleotides (ASOs), and CRISPR/Cas9 technology. The siRNA therapy has already achieved a remarkable feat by revolutionizing the treatment arena of cancers. Unlike small molecules and antibodies, which need administration every three months or even every two years, RNAi may be given every quarter to attain therapeutic results. In order to overcome complex challenges, delivering siRNAs to the targeted tissues and cells effectively and safely and improving the effectiveness of siRNAs in terms of their action, stability, specificity, and potential adverse consequences are required. In this context, the three primary techniques of siRNA therapies for hepatocellular carcinoma (HCC) are accomplished for inhibiting angiogenesis, decreasing cell proliferation, and promoting apoptosis, are discussed in this review. We also deliberate targeting issues, immunogenic reactions to siRNA therapy, and the difficulties with their intrinsic chemistry and transportation.

Implementing a School-Entry Mandate for the Human Papillomavirus Vaccine: Benefits and Challenges.

Human papillomavirus (HPV), a common sexually transmitted infection, has prompted the development of vaccines to mitigate associated cancer risks, particularly cervical cancer. Regions that have achieved a high rate of vaccination coverage are witnessing a transformative impact on public health, with a notable reduction of up to 30% in the incidence of cervical cancer cases. Emphasizing the broader impact of vaccination on public health, this review investigates the role of a school-entry mandate for the HPV vaccine, aiming to inform decisions about its potential benefits and challenges. With a focus on understanding the significance of vaccination, the review delves into its potential to reduce the physical, emotional, and financial burdens associated with HPV-associated cancers. Implementing school-entry mandates for the HPV vaccine offers benefits such as increased vaccination rates, protection against HPV-related diseases, and long-term health advantages. However, challenges include ethical concerns, parental opposition, and logistical issues. Successful implementation requires clear communication, collaboration, and education, with legal and ethical considerations addressing constitutional rights, liability concerns, autonomy, and equitable access. In summary, the implementation of school-entry mandates for the HPV vaccine offers the potential for increased vaccination rates and the reduction of health disparities. However, this approach is challenged by factors such as opposition, associated costs, and legal and ethical considerations. The decision to mandate the HPV vaccine requires a delicate balance between public health priorities and individual rights, necessitating clear communication, education, and collaborative efforts to address the complexities involved.

Seroprevalence of transfusion-transmitted infections among blood donors in Makkah, Saudi Arabia.

INTRODUCTION: Blood donation is vital for healthcare; however, transfusion-transmitted infections (TTIs) pose a serious risk. This study investigated the seroprevalence of TTIs among Saudi blood donors. METHODOLOGY: This retrospective study included male blood donors aged ≥ 18 years who donated blood at Al-Noor Specialist Hospital in Makkah from January 2017 to December 2022. The blood units were screened for hepatitis B surface antigen (HBsAg) and core antibodies (HBc-IgG), hepatitis C antibodies (HCV-Abs), syphilis, HIV-1 antigen/antibody (HIV-1 Ag/Ab), human T-lymphotropic virus 1, 2 (HTLV-1/2), and malaria. RESULTS: There were 40,287 donors with an average age of 44.33 ± 18.12 years, and 62.3% (n = 25103) were Saudis. The overall rate of TTIs seropositivity was 7.4% (n = 2953); HBc-IgG (6.1%; n = 2473) was the most common, followed by HCV-Abs (0.4%; n = 177), and syphilis (0.34%; n = 136). All cases were negative for malaria, whilst HIV and HTLV positive donors were 0.06% (n = 24) and 0.13% (n = 52), respectively. Syphilis was more prevalent among non-Saudis (0.24%; n = 83) than among Saudis (0.1%; n = 53), whereas anti-HBc antibodies seropositivity was significantly higher among Saudi (3.4%; n = 1373) than non-Saudi donors (2.7%; n = 1100). CONCLUSIONS: Hepatitis B virus was the most frequently detected bloodborne pathogen, followed by hepatitis C virus and syphilis. Hepatitis B virus was also more prevalent among Saudi donors, whilst expatriates had higher rates of syphilis. Additional prospective multicenter studies are needed to accurately determine the prevalence of TTIs in Saudi Arabia.

Serial Post-Operative Radiographs in Surgically Managed Pediatric Supracondylar Humeral Fractures: Are They Always Required?

Objective:  Supracondylar humeral fractures are among the most common pediatric fractures that require surgical intervention when displaced. Recent attention has been directed towards the utilization of serial radiographs in the post-operative period and their effect on decision-making. This study aimed to determine the usefulness of postoperative radiographs early post-operatively, with the goal of determining the optimal frequency for these radiographs. Methods: Pediatric patients who sustained a supracondylar humeral fracture and underwent operative intervention over a 15-year period were included in this study. Data were collected, including the baseline characteristics of the patients, fractures, and operative interventions. In addition, the time until healing, the total number of X-rays before K-wire removal, and postoperative function were evaluated. Results: A total of 122 pediatric patients were included, with a mean age of 5.33 ± 2.93 years. Most fractures were Gartland Type III (74.6%). Most fractures healed at 4 (36.1%) and 3 weeks (35.2%) after surgery. Of the cohort, 94.3% underwent four different x-rays before wire removal, with 4.9% requiring revision surgery. All revision cases were Gartland type 3, and for all cases, the decision to revise was made within three weeks of surgery. Conclusion: Routine post-fixation radiography should not be performed for surgically treated supracondylar humeral fractures before healing. An exception is the Gartland type 3 fracture, for which earlier imaging may be indicated.

Circulating tumor DNA (ctDNA) application in investigation of cancer: Bench to bedside.

Now, genomics forms the core of the precision medicine concept. Comprehensive investigations of tumor genomes have made it possible to characterize tumors at the molecular level and, specifically, to identify the fundamental processes that cause condition. A variety of kinds of tumors have seen better outcomes for patients as a result of the development of novel medicines to tackle these genetic-driving processes. Since therapy may exert selective pressure on cancers, non-invasive methods such as liquid biopsies can provide the opportunity for rich reservoirs of crucial and real-time genetic data. Liquid biopsies depend on the identification of circulating cells from tumors, circulating tumor DNA (ctDNA), RNA, proteins, lipids, and metabolites found in patient biofluids, as well as cell-free DNA (cfDNA), which exists in those with cancer. Although it is theoretically possible to examine biological fluids other than plasma, such as pleural fluid, urine, saliva, stool, cerebrospinal fluid, and ascites, we will limit our discussion to blood and solely cfDNA here for the sake of conciseness. Yet, the pace of wider clinical acceptance has been gradual, partly due to the increased difficulty of choosing the best analysis for the given clinical issue, interpreting the findings, and delaying proof of value from clinical trials. Our goal in this review is to discuss the current clinical value of ctDNA in cancers and how clinical oncology systems might incorporate procedures for ctDNA testing.

The utility of serum glucose potassium ratio as a predictive factor for haemorrhagic transformation, stroke recurrence, and mortality among ischemic stroke patients.

Background and Objective: Glucose-Potassium Ratio (GPR) has emerged as a biomarker in several pathophysiological conditions. However, the association between GPR and long-term outcomes in stroke patients has not been investigated. Our study evaluated the applicability of baseline GPR as a predictive prognostic tool for clinical outcomes in ischemic stroke patients. Methods: The multicenter retrospective cohort study included acute-subacute adult ischemic stroke patients who had their baseline serum GPR levels measured. Eligible patients were categorized into two sub-cohorts based on the baseline GPR levels (<1.67 vs. ≥ 1.67). The primary outcome was the incidence of 30-day hemorrhagic transformation, while stroke recurrence, and all-cause mortality within twelve months, were considered secondary. Results: Among 4083 patients screened, 1047 were included in the current study. In comparison with GPR < 1.67 group, patients with ≥ 1.67 GPR had a significantly higher ratio of all-cause mortality within twelve months (aHR 2.07 [95 % CI 1.21-3.75] p = 0.01), and higher ratio of 30-day hemorrhagic transformation but failed to reach the statistical significance (aHR 1.60 [95 % CI 0.95-2.79], p = 0.08). Conclusion: Overall, baseline GPR serum is an independent predictor of all-cause mortality within twelve months in patients with acute and subacute ischemic stroke. Further clinical studies are necessary to validate these findings.

Hemp Seed Oil Inhibits the Adipogenicity of the Differentiation-Induced Human Mesenchymal Stem Cells through Suppressing the Cannabinoid Type 1 (CB1).

Central and peripheral mechanisms of the endocannabinoid system (ECS) favor energy intake and storage. The ECS, especially cannabidiol (CBD) receptors, controls adipocyte differentiation (hyperplasia) and lipid accumulation (hypertrophy) in adipose tissue. In white adipose tissue, cannabidiol receptor 1 (CB1) stimulation increases lipogenesis and inhibits lipolysis; in brown adipose tissue, it decreases mitochondrial thermogenesis and biogenesis. This study compared the availability of phytocannabinoids [CBD and Δ9-tetrahydrocannabinol (THC)] and polyunsaturated fatty acids [omega 3 (ω3) and omega 6 (ω6)] in different hemp seed oils (HSO). The study also examined the effect of HSO on adipocyte lipid accumulation by suppressing cannabinoid receptors in adipogenesis-stimulated human mesenchymal stem cells (hMSCs). Most importantly, Oil-Red-O' and Nile red tests showed that HSO induced adipogenic hMSC differentiation without differentiation agents. Additionally, HSO-treated cells showed increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to controls (hMSC). HSO reduced PPARγ mRNA expression after differentiation media (DM) treatment. After treatment with HSO, DM-hMSCs had significantly lower CB1 mRNA and protein expressions than normal hMSCs. HSO treatment also decreased transient receptor potential vanilloid 1 (TRPV1), fatty acid amide hydrolase (FAAH), and monoacylglycerol lipase (MGL) mRNAs in hMSC and DM-hMSCs. HSO treatment significantly decreased CB1, CB2, TRPV1, and G-protein-coupled receptor 55 (GPCR55) protein levels in DM-hMSC compared to hMSC in western blot analysis. In this study, HSO initiated adipogenic differentiation in hMSC without DM, but it suppressed CB1 gene and protein expression, potentially decreasing adipocyte lipid accumulation and lipogenic enzymes.

Respiratory Syncytial Virus (RSV) Burden in Infants in the Kingdom of Saudi Arabia and the Impact of All-Infant RSV Protection: A Modeling Study.

INTRODUCTION: Respiratory syncytial virus (RSV) represents a considerable burden on the healthcare system and hospital resources. This study explored the impact of universal immunoprophylaxis with long-acting monoclonal antibody (nirsevimab) during infants' first RSV season on RSV-induced health events and related costs in the Kingdom of Saudi Arabia (KSA). METHODS: The burden of RSV-induced health events and related costs under the current standard of practice (SoP) and the impact of universal immunoprophylaxis with nirsevimab was estimated using a static decision-analytic model in a cohort of infants experiencing their first RSV season in the KSA. The model estimated hospital admissions (including pediatric intensive care unit [PICU] admissions and mechanical ventilation [MV]), emergency room (ER) visits, primary care (PC) visits, long-term sequelae, and RSV mortality. RESULTS: The model estimated that under the current SoP, RSV results in 17,179-19,607 hospitalizations (including 2932-3625 PICU and 172-525 MV admissions), 57,654-191,115 ER visits, 219,053-219,970 PC visits, 14 deaths, 12,884-14,705 cases of recurrent wheezing, and a total cost of SAR 480-619 million. Universal nirsevimab immunoprophylaxis was estimated to avert 58% of hospitalizations (58% PICU admissions, 58% MV episodes), 53% of ER visits, 53% of PC visits, 58% of episodes of recurrent wheezing, 8 deaths, and result in savings of SAR 274-343 million in total healthcare cost. CONCLUSION: Compared with current SoP, an nirsevimab immunoprophylaxis strategy in the KSA for all infants during their first RSV season was estimated to dramatically decrease healthcare resource use, and economic burden associated with RSV.

Cam-type hip morphology in asymptomatic patients.

BACKGROUND: The alpha angle has been widely used in the assessment of cam-type of impingement, but recent studies have shown that this angle may also be high in asymptomatic patients. The aim of this study is to report the prevalence of cam-type morphology in asymptomatic volunteers and explore its correlation with hip clinical and radiological parameters. METHODS: This single-centre prospective study included 48 asymptomatic male volunteers (96 hips). All candidates fulfilled the inclusion and exclusion criteria. Physical examination and 1.5 -T MRI imaging were done for bilateral hips on the same day. Alpha angle measurements were obtained from 4 different positions and cam-type morphology was considered positive using 2 different cut points >55° and >60°. Descriptive statistics were analysed and correlations were performed where appropriate and p-value < 0.05 was considered to be significant. RESULTS: The prevalence of cam-type morphology using alpha angle >55° was 68.8%, 87.5%, 50% and 34.4% in the 12, 1, 2 and 3 o'clock positions respectively. While it was 38.5%, 69.8%, 26% and 12.5% in the 12, 1, 2 and 3 o'clock positions of the studied hips respectively using alpha angle >60°. The maximum alpha angle was more frequently prevalent at the 1 o'clock position in 71 (74%). Labral tear was detected in 26 (27.1%) hips and impingement test was positive in 12 (12.5%) hips. There was no correlation between the presence of cam-type morphology and range of motion of the hip, presence of positive impingement test nor labral tears. CONCLUSIONS: Cam-type morphology prevalence is high among asymptomatic males, and mostly pronounced at the 1 o'clock position. A correlation between high alpha angle and positive impingement test or labral tear was not found in our cohort. Future studies are required to determine the natural history of asymptomatic cam-type morphology and risk of hip derangement.

Time of surgery and surgeon level in supracondylar humerus fractures in pediatric patients: A retrospective study.

BACKGROUND: Supracondylar humerus fractures account for more than 60% of all elbow fractures and about 1/5 of all pediatric fractures. Unfortunately, these fractures can be associated with risk of complications including neurovascular injuries, malunions and limb deformities. Controversy exists regarding the effect of time of surgical intervention and/or level of surgeon performing the surgery on outcome of these fractures. AIM: To determine whether time of surgical intervention and/or surgeon level influence the outcomes of surgically managed pediatric supracondylar humerus fractures. METHODS: We retrospectively studied 155 pediatric patients presenting with a supracondylar humerus fracture in a level 1 trauma center from January 2006 to December 2019. The data extracted included demographic data, fracture characteristics, surgical data, and follow-up outcomes. The collected data was analyzed and P values of < 0.05 were considered statistically significant. RESULTS: Of the cohort, 11% of patients had documented post-operative complications, of which the majority occurred in surgeries performed after day time working hours and in fractures requiring open reduction. While the lowest complication rate was found in surgeries performed by pediatric orthopaedic surgeons, this did not reach statistical significance. CONCLUSION: In pediatric patients undergoing surgery for supracondylar fractures, we found a higher complication rate when surgeries were not performed during working hours. Surgeon level and training had no significant effect on the risk of post-operative complications.

The Impact of Non-pharmacological Interventions on Blood Pressure Control in Patients With Hypertension: A Systematic Review.

Hypertension treatment should involve non-pharmacological interventions such as dietary salt restriction, weight loss, exercise, limiting alcohol intake, and dietary approaches to stop hypertension diet. Significant impacts of these interventions have been suggested for a long time. This systematic review aims to assess the influence of non-pharmacological therapies on hypertension patients' ability to control their blood pressure. The review will concentrate on randomized controlled trials examining how non-pharmacological therapies affect blood pressure regulation in hypertension patients. A systematic review was conducted to investigate the impact of non-pharmacological interventions on blood pressure control in patients with hypertension. A comprehensive search for relevant studies was conducted. The following electronic databases were searched: EMBASE, OVID-MEDLINE, and PubMed. The search covered the period between January 2000 and August 2023. The search strategy included a combination of keywords related to hypertension, non-pharmacological interventions, and blood pressure control. A thorough literature evaluation of papers from the EMBASE, OVID-MEDLINE, and PubMed databases was part of the procedure for choosing the studies. Combinations of the keywords telemedicine, primary care, and effectiveness were used for the search. Only studies published in English between January 2000 and August 2023 were included in the search. Through database searching, 862 entries were found, of which 321 were from EMBASE, 112 from OVID-MEDLINE, and 429 from PubMed. After duplicate records were eliminated, 117 records were checked for eligibility. Of these, 100 were disregarded for a variety of reasons, including not relevant to the objectives of the study (n = 63), abstracts or reviews (n = 8), and studies that failed to present interesting research findings (n = 36). The eligibility of the remaining 10 full-text publications was evaluated. Ten articles passed the inclusion tests and were added to the research after a thorough evaluation. Lifestyle modifications are important and have a significant impact on controlling hypertension and a positive impact on reducing blood pressure. Combination therapy is more effective; however, adherence to the modifications is the most important factor affecting the outcomes.

Late brachial plexopathy after a mid-shaft clavicle fracture: A case report.

BACKGROUND: Clavicle fractures can rarely be associated with brachial plexus injury. These are commonly caused by tractional injury at the time of trauma, but unfrequently can be caused by compression of the brachial plexus from excessive callus or granulation tissue formation. CASE SUMMARY: We report a rare case of an adult male who sustained a mid-shaft clavicle fracture and had a late presentation of brachial plexus palsy due to compression from excessive callus formation. CONCLUSION: We reported a case of a rare occurrence of delayed brachial plexus palsy due to compression from excessive callus formation in a midshaft clavicle fracture. Early diagnosis and surgical decompression of the brachial plexus is critical, as when managed efficiently, a full recovery of the brachial plexus palsy can be expected in these patients.

Dual plate fixation of proximal humerus fractures: Retrospective review and surgical technique.

Introduction: Recent interest has been directed towards dual plate fixation for comminuted proximal humerus fractures, with an aim to improve construct stability and thus improve patient outcomes while decreasing the risk of fracture-associated complications. We present our experience with this technique in a case series of patients with proximal humerus fractures and describe our surgical technique. Methodology: This was a single-center retrospective case series of patients presenting with an acute (<6 weeks) proximal humerus fracture who underwent ORIF with dual plating fixation. Patient, fracture, and surgical data were collected. All patient outcomes were evaluated using Constant-Murley shoulder score and Single Assessment Numeric Evaluation. Results: Our series included nine patients with a mean age of 46.2 years (range: 27-70 years old). All fractures healed within 4 months and no complications were encountered. At 1 year follow-up, the mean SANE score was 69.4% and the mean Constant Murley shoulder score was 78.9 (range: 70-96). Conclusion: Our current series shows that applying the dual plating technique in severely comminuted proximal humerus fractures provides adequate fixation and thus good patient outcomes. Further research is required before this technique can be strongly recommended for management of these complex fractures. Level of Evidence: Level 5.

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study.

Introduction: Several studies have shown increased incidence, recurrence, and severity of Clostridium difficile infection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. Methods: This was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. Result: There was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. Conclusion: Biologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.

Optimal entry point for antegrade and retrograde femoral intramedullary nails.

Surgical management of femoral shaft fractures with intramedullary nails has become the standard of care, with multiple options for entry point described, including piriformis entry, trochanter entry and retrograde femoral nails. Our present review describes the surgical anatomy of the proximal and distal femur and its relation to different entry points for intramedullary femoral nails. In addition, we reviewed relative indications for each technique, difficulties associated and possible complications.

New Succinimide-Thiazolidinedione Hybrids as Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies.

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue's resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide-thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (10a-e). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound 10d was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound 10d was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound 10d was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

Knowledge of and Testing Rate for Hepatitis C Infection among the General Public of Saudi Arabia: A Cross-Sectional Study.

INTRODUCTION: The Ministry of Health in Saudi Arabia has announced a plan to eradicate hepatitis C virus (HCV) infection. This study sought to evaluate the knowledge levels and testing rate among the general population of Saudi Arabia. METHODS: A cross-sectional study was conducted using data collected from an online, self-administered survey. Multivariable analysis was conducted using multiple binary logistic regression models to identify factors associated with low knowledge levels as well as predictors of HCV testing. RESULTS: A total of 689 participants completed the survey. While most participants (88%) have heard of HCV infection, less than half (47.3%) understood that HCV is curable with medications. More than half of the participants (53.7%) have low knowledge about HCV infection. Testing for HCV was reported by 123 respondents (17.8%), and the odds of testing for HCV were significantly lower among residents of the Makkah region (OR = 0.59 [95% CI: 0.36-0.97]) and those with low knowledge level (OR = 0.47 [95% CI: 0.29-0.74]). HCV diagnosis was reported by nine respondents (1.3%), of whom only four reported receiving treatment (44%). CONCLUSIONS: Our study indicates inadequate knowledge levels and relatively low testing rate. These findings underscore the need for national awareness campaigns and more effective strategies for HCV screening.

Incidence and Risk Factors for Retinal Detachment Following Cataract Surgery at a Tertiary Center in Jeddah, Saudi Arabia.

Introduction The incidence of retinal detachment in the general population is 0.08%, it has been reported to reach 0.7% or higher following cataract surgery. One of the most important risk factors for retinal detachment is posterior capsular rupture during cataract surgery. Additional risk factors include high myopia, history of ocular trauma, young age, male sex, and diabetes. In this study, we aimed to investigate the incidence and risk factors of retinal detachment following cataract surgery in patients treated at our hospital. Materials and methods This retrospective cohort study was conducted at King Abdulaziz University Hospital (KAUH), a tertiary center in Jeddah, Saudi Arabia. The medical records of 365 patients (365 eyes) who underwent cataract surgery from 2017 to 2021 were reviewed. Results The average age of the 365 patients was 63 years, and 47.7% (n=174) of patients were male. The incidence of retinal detachment was 3.3% (n=12). The risk of RD was 2.8 times higher for the right eye than for the left eye. The incidence of RD was significantly more in eyes with intraoperative posterior capsular rupture, zonular dehiscence, corneal trauma, and surgery combined with anterior vitrectomy than in other eyes. The most common complication of cataract surgery is corneal edema, which was observed in 22.7% of the eyes; our analysis revealed a significant relationship between corneal edema and the duration of surgery. Conclusion In our study, we highlighted the higher incidence of retinal detachment compared to those in other studies; most cases occurred one month postoperatively.

Satisfactory outcomes of post-operative subtalar extra-articular arthroereisis in juvenile flexible flat foot.

OBJECTIVES: To analyze the surgical outcomes of subtalar extra-articular arthroereisis and the patient/parent satisfaction regarding the foot's shape, foot pain, ability to walk, ability to jump, and shoe wear. METHODS: Our retrospective cross-sectional study was carried out through an online-based questionnaire to assess patient satisfaction postoperatively at 3 hospitals (King Khalid University Hospital, Sultan bin Abdulaziz Humanitarian City, and Dallah Hospital, Riyadh, Saudi Arabia) between the years 2014-2021. RESULTS: A total of 65 patients participated in our study. Approximately 86.1% of them had the operation bilaterally. The most important aspects where patients noticed the most improvement were the foot's shape (90.8%), pain (81.5%), and ability to walk (76.9%). CONCLUSION: Several studies have been carried out highlighting the surgical technique and complications of the procedure. However, a limited number of studies have been carried out to assess patient satisfaction with the procedure, especially in Saudi Arabia, as the procedure is considered relatively new in the region with insufficient data regarding it. Therefore, this study is considered one of the few articles regarding subtalar extra-articular arthroereisis in the region.

Drug Inhibition of Redox Factor-1 Restores Hypoxia-Driven Changes in Tuberous Sclerosis Complex 2 Deficient Cells.

Therapies with the mechanistic target of rapamycin complex 1 (mTORC1) inhibitors are not fully curative for tuberous sclerosis complex (TSC) patients. Here, we propose that some mTORC1-independent disease facets of TSC involve signaling through redox factor-1 (Ref-1). Ref-1 possesses a redox signaling activity that stimulates the transcriptional activity of STAT3, NF-kB, and HIF-1α, which are involved in inflammation, proliferation, angiogenesis, and hypoxia, respectively. Here, we demonstrate that redox signaling through Ref-1 contributes to metabolic transformation and tumor growth in TSC cell model systems. In TSC2-deficient cells, the clinically viable Ref-1 inhibitor APX3330 was effective at blocking the hyperactivity of STAT3, NF-kB, and HIF-1α. While Ref-1 inhibitors do not inhibit mTORC1, they potently block cell invasion and vasculature mimicry. Of interest, we show that cell invasion and vasculature mimicry linked to Ref-1 redox signaling are not blocked by mTORC1 inhibitors. Metabolic profiling revealed that Ref-1 inhibitors alter metabolites associated with the glutathione antioxidant pathway as well as metabolites that are heavily dysregulated in TSC2-deficient cells involved in redox homeostasis. Therefore, this work presents Ref-1 and associated redox-regulated transcription factors such as STAT3, NF-kB, and HIF-1α as potential therapeutic targets to treat TSC, where targeting these components would likely have additional benefits compared to using mTORC1 inhibitors alone.