Browse publications by year: 2023

  1. Teh LA
    Cureus, 2023 Jul;15(7):e41250.
    PMID: 37529802 DOI: 10.7759/cureus.41250
    Extrusion of root filling material had been shown to reduce the success of endodontic treatment. This case report describes the management of a patient who reported prolonged, persistent, and increasing pain on an upper root filled central incisor with extruded root filling material. A 28-year-old female patient came with the chief complaint of pain and tenderness on the upper left central incisor. The pain was mostly triggered by mastication. Upon examination and investigation, the tooth of concern was tooth 21 which was a root treated many years ago. It appeared to have tenderness on percussion and palpation. Non-surgical root canal retreatment was completed on tooth 21. However, the patient complained of the same pain while biting even after six months post-obturation. Therefore, endodontic microsurgery was performed to remove the root filling material that was extruded and to enucleate the granulomatous lesion around the periapical region of tooth 21. After enucleation, apical root end resection was performed. Postoperatively, the patient reported comfort and no pain and was able to resume her daily activities. At six months of review, the radiograph showed evidence of complete healing. This case report captured the importance of endodontic microsurgery as a viable treatment option where nonsurgical root canal retreatment failed to relieve the patient's symptoms.
  2. Zainuddin MZ, Mohamad NS, Su Keng T, Mohd Yusof MYP
    J Forensic Sci, 2023 Nov;68(6):2048-2056.
    PMID: 37529884 DOI: 10.1111/1556-4029.15352
    Conventional dental age estimation relies on destructive methods such as sectioning and staining, which are unpreferable when the tooth is required for evidential or archeological preservation. MicroCT is a non-destructive, high-resolution imaging technique that allows for accurate morphometrical measurement. Although microCT technology has been applied in a variety of dental studies, studies focusing on dental age-related change and dental age estimation based on microCT imaging remain lacking. Based on the question: "How has microCT technology been applied in studying human age-related tooth morphological change and dental age estimation studies?", the authors conducted a scoping review in accordance with the Arksey and O'Malley (2005) and the PRISMA-ScR guidelines. A literature search using five major scientific databases identified 452 articles, with 11 full-text articles being eligible to be included in the scoping review. Furthermore, 6 out of the 11 studies performed dental age estimation modeling. An overview of the parameters used in the selected articles revealed a variety of tooth characteristics, such as pulp cavity to whole tooth volume ratio, secondary dentin, as well as the diameter of root canal orifice. The findings of this scoping review highlight the extent microCT is used in studying dental age-related changes, as well as the effectiveness of microCT in dental age estimation studies. This review serves as a guide for future forensic odontology age estimation studies.
    MeSH terms: Humans; Research; X-Ray Microtomography/methods
  3. Kabir MZ, Tayyab H, Erkmen C, Mohamad SB, Uslu B
    J Biomol Struct Dyn, 2023 Aug 02.
    PMID: 37529911 DOI: 10.1080/07391102.2023.2239931
    Biomolecular association of an anticancer drug, leflunomide (LEF) with human serum albumin (HSA), the leading ligands carrier in human circulation was characterized using biophysical (i.e., fluorescence, absorption and voltammetric) methods and computational (i.e., molecular docking and molecular dynamics simulation) techniques. Evaluations of fluorescence, absorption and voltammetric findings endorsed the complex formation between LEF and HSA. An inverse relationship of Stern-Volmer constant-temperature and hyperchromic shift of the protein's absorption signal with addition of LEF confirmed the LEF quenched the HSA fluorescence through static process. Moderate nature of binding strength (binding constant = 2.76-4.77 × 104 M-1) was detected towards the LEF-HSA complexation, while the association process was naturally driven via hydrophobic interactions, van der Waals interactions and hydrogen bonds, as evident from changes in entropy (ΔS= + 19.91 J mol-1 K-1) and enthalpy (ΔH = - 20.09 kJ mol-1), and molecular docking assessments. Spectral analyses of synchronous and three-dimensional fluorescence validated microenvironmental fluctuations near Trp and Tyr residues upon LEF binding to the protein. LEF association with HSA significantly defended temperature-induced destabilization of the protein. Although LEF was found to attach to HSA at Sudlow's sites I and II, but exhibited greater preference toward its site I, as detected by the investigations of competitive site-marker displacement. Molecular dynamics simulation assessment revealed that the complex attained equilibrium throughout simulations, showing the LEF-HSA complex constancy.Communicated by Ramaswamy H. Sarma.
  4. Ahmad Alwi NA, Lim SM, Mani V, Ramasamy K
    J Diet Suppl, 2023;20(5):717-734.
    PMID: 35876040 DOI: 10.1080/19390211.2022.2103608
    This study explored mechanisms underpinning enhanced memory in amyloid precursor protein (APP) transgenic mice (male; 10-12 months; n = 6/group) supplemented with Lactobacillus plantarum LAB12 (LAB12)/Lactobacillus casei Shirota (LcS). Morris Water Maze test was performed before brains were harvested for gene expression and biochemical studies. LAB-supplemented mice exhibited reduced escape latency and distance but significant increased time spent in platform zone. This was associated with downregulated beta-site APP cleaving enzyme-1 (BACE1) mRNA and significant reduced nitric oxide in brains. LAB12 also significantly increased glutathione. The LAB-enhanced memory is strain-dependent and could be mediated, in part, through amyloidogenic pathway and anti-oxidant/oxidative stress interplay.
    MeSH terms: Alzheimer Disease*; Animals; Antioxidants/metabolism; Disease Models, Animal; Lactobacillus; Male; Mice, Transgenic; Amyloid beta-Peptides; Aspartic Acid Endopeptidases/genetics; Aspartic Acid Endopeptidases/metabolism; Oxidative Stress; Mice; Amyloid Precursor Protein Secretases/genetics; Amyloid Precursor Protein Secretases/metabolism
  5. Rosli AA, Azlan A, Rajasegaran Y, Mot YY, Heidenreich O, Yusoff NM, et al.
    Clin Exp Med, 2023 Aug;23(4):1137-1159.
    PMID: 36229751 DOI: 10.1007/s10238-022-00913-1
    Chromosomal abnormalities in acute myeloid leukemia (AML) have significantly contributed to scientific understanding of its molecular pathogenesis, which has aided in the development of therapeutic strategies and enhanced management of AML patients. The diagnosis, prognosis and treatment of AML have also rapidly transformed in recent years, improving initial response to treatment, remission rates, risk stratification and overall survival. Hundreds of rare chromosomal abnormalities in AML have been discovered thus far using chromosomal analysis and next-generation sequencing. As a result, the World Health Organization (WHO) has categorized AML into subgroups based on genetic, genomic and molecular characteristics, to complement the existing French-American classification which is solely based on morphology. In this review, we aim to highlight the most clinically relevant chromosomal aberrations in AML together with the technologies employed to detect these aberrations in laboratory settings.
    MeSH terms: Chromosome Aberrations; Genetic Testing; Humans; Prognosis; Cytogenetic Analysis
  6. Rizwi FA, Abubakar M, Puppala ER, Goyal A, Bhadrawamy CV, Naidu VGM, et al.
    PMID: 37522565 DOI: 10.1615/JEnvironPatholToxicolOncol.2023045403
    According to the World Health Organization (WHO), cancer is the second-highest cause of mortality worldwide, killing nearly 9.6 million people annually. Despite the advances in diagnosis and treatment during the last couple of decades, it remains a serious concern due to the limitations of currently available cancer management strategies. Therefore, alternative strategies are highly required to overcome these glitches. In addition, many etiological factors such as environmental and genetic factors initiate the activation of the Janus kinase (JAK)-signal transducer and activator of the transcription (STAT) pathway. This aberrant activation of the JAK-STAT pathway has been reported in various disease states, including inflammatory conditions, hematologic malignancies, and cancer. For instance, many patients with myeloproliferative neoplasms carry the acquired gain-of-function JAK2 V617F somatic mutation. This knowledge has dramatically improved our understanding of pathogenesis and has facilitated the development of therapeutics capable of suppressing the constitutive activation of the JAK-STAT pathway. Our aim is not to be expansive but to highlight emerging ideas towards preventive therapy in a modern view of JAK-STAT inhibitors. A series of agents with different specificities against different members of the JAK family of proteins is currently undergoing evaluation in clinical trials. Here we give a summary of how JAK-STAT inhibitors function and a detailed review of current clinical drugs for managing cancer as a new therapeutic approach.
    MeSH terms: Humans; Signal Transduction; STAT Transcription Factors/genetics; STAT Transcription Factors/metabolism; Janus Kinases/genetics; Janus Kinases/metabolism
  7. Jimi N, Shinji J, Hookabe N, Okanishi M, Woo SP, Nakano T
    Zoolog Sci, 2023 Aug;40(4):308-313.
    PMID: 37522602 DOI: 10.2108/zs220057
    A new fish leech, Branchellion brevicaudatae sp. n., is described based on specimens parasitizing the gills of the short-tail stingray, Bathytoshia brevicaudata (Hutton, 1875), collected from Japanese waters. The new species can be distinguished from other congeners by having: i) pulsating vesicles emerging from posterior base of branchiae, one pair per somite; ii) dorsal white spots, not arranged in longitudinal row; and iii) blackish body. A phylogenetic tree based on partial sequences of the mitochondrial cytochrome c oxidase subunit I gene from the new species and other piscicolid worms showed that the new species is sister to Branchellion torpedinis Savigny, 1822. This is the first record of Branchellion Savigny, 1822 from Japanese waters.
    MeSH terms: Animals; Gills; Leeches*; Phylogeny; Skates (Fish)*; Tail
  8. Khoo LS, Lai PS, Siew SF, Ibrahim MA
    PMID: 37523136 DOI: 10.1007/s12024-023-00683-6
    Managing mass fatality incidents or disasters involving multiple deaths are not uncommon among forensic practitioners. In fact, management of unidentified or unknown bodies is also a vital component of the day-to-day mortuary work practice. The unidentified and subsequently unclaimed bodies have always been a "silent mass disaster," a problem that needs to be tackled within the forensic community and raises the global issue of ethics, law, and human rights. Unidentified bodies' in Malaysia make up an average of 4.02% of all death cases where a total postmortem examination was performed which is comparable with other developing countries within 4-10% which can go up to 25%. Moreover, unstandardized procedures in all mortuaries in different states and districts in Malaysia have worsened the scenario even with guidelines in place. This study aims to address the issues surrounding unidentified and unclaimed bodies including body disposal from a social and legal perspective using case study methodology by comparing four different countries in the Asia Pacific Region through document analysis and interview methods. One of the major findings is evident in 3 out of the 4 models, whereby there is a considerable gap in consolidating the missing person report and information to match with the unidentified bodies received in forensic institutions in an attempt to enhance the identification process which ultimately intends as a closure for the family members. It is also timely to think out of the box beyond dental records and DNA profiling to improve the identification rate for skeletonized remains through means of anthropology biometrics comparison. With the limited literature published surrounding this domain, it is hoped that the suggestions and recommendations to standardize the management of unidentified and unclaimed bodies can benefit many forensic institutions and public mortuaries in this region.
  9. Phu DH, Maneerattanasak S, Shohaimi S, Trang LTT, Nam TT, Kuning M, et al.
    PLoS One, 2023;18(7):e0289382.
    PMID: 37523396 DOI: 10.1371/journal.pone.0289382
    Mental health disorders have become a growing public health concern among individuals recovering from COVID-19. Long COVID, a condition where symptoms persist for an extended period, can predict psychological problems among COVID-19 patients. This study aimed to investigate the prevalence of long COVID and mental health status among Thai adults who had recovered from COVID-19, identify the association between the mental health status and long COVID symptoms, and investigate the risk factors associated with the correlation between long COVID and mental health outcomes. A cross-sectional study was conducted among 939 randomly selected participants in Nakhon Si Thammarat province, southern Thailand. The Depression, Anxiety, and Stress Scale-21 was used to investigate mental health symptoms, and a checklist comprised of thirteen common symptoms was used to identify the long COVID among participants. Logistic regression models were used to investigate the risk factors associated with mental health status and long COVID symptoms among participants. Among the 939 participants, 104 (11.1%) had depression, 179 (19.1%) had anxiety, and 42 (4.8%) were stressed. A total of 745 participants (79.3%) reported experiencing at least one symptom of long COVID, with fatigue (72.9%, SE±0.02), cough (66.0%, SE±0.02), and muscle pain (54.1%, SE±0.02) being the most frequently reported symptoms. All long COVID symptoms were significantly associated with mental health status. Shortness of breath, fatigue, and chest tightness were the highest risk factors for mental health status among COVID-19 patients. The final multivariable model indicated that female patients (OR = 1.89), medical history (OR = 1.92), and monthly income lower than 5,000 Thai baht (OR = 2.09) were associated with developing long COVID symptoms and mental health status (all p<0.01). This study provides valuable insights into the potential long-term effects of COVID-19 on mental health and enhances understanding of the mechanisms underlying the condition for predicting the occurrence of mental health issues in Thai COVID-19 patients.
    MeSH terms: Adult; Anxiety/etiology; Anxiety/epidemiology; Cross-Sectional Studies; Depression/etiology; Depression/epidemiology; Female; Health Status; Humans; Thailand/epidemiology; Prevalence
  10. Aljrees T, Cheng X, Ahmed MM, Umer M, Majeed R, Alnowaiser K, et al.
    PLoS One, 2023;18(7):e0287298.
    PMID: 37523404 DOI: 10.1371/journal.pone.0287298
    The proliferation of fake news has severe effects on society and individuals on multiple fronts. With fast-paced online content generation, has come the challenging problem of fake news content. Consequently, automated systems to make a timely judgment of fake news have become the need of the hour. The performance of such systems heavily relies on feature engineering and requires an appropriate feature set to increase performance and robustness. In this context, this study employs two methods for reducing the number of feature dimensions including Chi-square and principal component analysis (PCA). These methods are employed with a hybrid neural network architecture of convolutional neural network (CNN) and long short-term memory (LSTM) model called FakeNET. The use of PCA and Chi-square aims at utilizing appropriate feature vectors for better performance and lower computational complexity. A multi-class dataset is used comprising 'agree', 'disagree', 'discuss', and 'unrelated' classes obtained from the Fake News Challenges (FNC) website. Further contextual features for identifying bogus news are obtained through PCA and Chi-Square, which are given nonlinear characteristics. The purpose of this study is to locate the article's perspective concerning the headline. The proposed approach yields gains of 0.04 in accuracy and 0.20 in the F1 score, respectively. As per the experimental results, PCA achieves a higher accuracy of 0.978 than both Chi-square and state-of-the-art approaches.
    MeSH terms: Engineering*; Humans; Judgment; Neural Networks (Computer)
  11. Nosratabadi S, Ashtary-Larky D, Hosseini F, Namkhah Z, Mohammadi S, Salamat S, et al.
    Diabetes Metab Syndr, 2023 Aug;17(8):102824.
    PMID: 37523928 DOI: 10.1016/j.dsx.2023.102824
    BACKGROUND AND AIM: It has been suggested that taking vitamin C supplements may improve glycemic control in patients with type 2 diabetes mellitus (T2DM). However, there has not been a thorough evaluation of the actual impact or certainty of the findings. This systematic review and meta-analysis was conducted to determine the effect of vitamin C supplementation on glycemic profile in T2DM patients.

    METHODS: A systematic search was performed across online databases including Scopus, Web of Science, and PubMed/Medline to identify relevant randomized controlled trials (RCTs) published until July 2022. A random-effects model was applied for the meta-analysis.

    RESULTS: The present meta-analysis included a total of 22 RCTs with 1447 patients diagnosed with T2DM.A pooled analysis revealed a significant decrease in levels of serum hemoglobin A1c (HbA1c), fasting insulin, and fasting blood glucose (FBG) in vitamin C-treated T2DM patients compared with their untreated counterparts. The dose-response evaluation displayed a substantial linear association between the intervention duration and changes in serum HbA1c levels. However, the analysis did not demonstrate any significant effect of vitamin C on serum values of homeostasis model assessment of insulin resistance(HOMA-IR) in diabetic patients. Subgroup analyses indicated that high-dose vitamin C administration (≥1000 mg/d) considerably decreased serum HOMA-IR levels.

    CONCLUSION: These findings suggest that long-term (≥12 weeks) and high-dose vitamin C supplementation (≥1000 mg/d) may ameliorate glycemic profile in T2DM patients. However, additional high-quality RCTs are necessary to validate these results.

    MeSH terms: Ascorbic Acid/therapeutic use; Hemoglobin A, Glycosylated; Humans; Vitamin D; Vitamins/therapeutic use; Dietary Supplements
  12. Chen JW, Liew FF, Tan HW, Misran M, Chung I
    Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):346-360.
    PMID: 37524112 DOI: 10.1080/21691401.2023.2237534
    Extracellular vesicles (EVs) are small vesicles that are naturally released by cells and play a crucial role in cell-to-cell communication, tissue repair and regeneration. As naturally secreted EVs are limited, liposomes with different physicochemical properties, such as 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and linoleic acid (LA) with modifications have been formulated to improve EVs secretion for in vitro wound healing. Various analyses, including dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to monitor the successful preparation of different types of liposomes. The results showed that cholesterol-LA liposomes significantly improved the secretion of EVs from immortalized adipose-derived mesenchymal stem cells (AD-MSCs) by 1.5-fold. Based on the cell migration effects obtained from scratch assay, both LA liposomal-induced EVs and cholesterol-LA liposomal-induced EVs significantly enhanced the migration of human keratinocytes (HaCaT) cell line. These findings suggested that LA and cholesterol-LA liposomes that enhance EVs secretion are potentially useful and can be extended for various tissue regeneration applications.
    MeSH terms: Cell Movement; Cholesterol; Humans; Liposomes/metabolism; Linoleic Acid/analysis; Linoleic Acid/metabolism
  13. Jagaba AH, Lawal IM, Ghfar AA, Usman AK, Yaro NSA, Noor A, et al.
    Chemosphere, 2023 Oct;339:139620.
    PMID: 37524265 DOI: 10.1016/j.chemosphere.2023.139620
    Agro-industrial biorefinery effluent (AIBW) is considered a highly polluting source responsible for environmental contamination. It contains high loads of chemical oxygen demand (COD), and phenol, with several other organic and inorganic constituents. Thus, an economic treatment approach is required for the sustainable discharge of the effluent. The long-term process performance, contaminant removal and microbial response of AIBW to rice straw-based biochar (RSB) and biochar-based geopolymer nanocomposite (BGC) as biosorbents in an activated sludge process were investigated. The adsorbents operated in an extended aeration system with a varied hydraulic retention time of between 0.5 and 1.5 d and an AIBW concentration of 40-100% for COD and phenol removal under standard conditions. Response surface methodology was utilised to optimize the process variables of the bioreactor system. Process results indicated a significant reduction of COD (79.51%, 98.01%) and phenol (61.94%, 74.44%) for BEAS and GEAS bioreactors respectively, at 1 d HRT and AIBW of 70%. Kinetic model analysis indicated that the Stover-Kincannon model best describes the system functionality, while the Grau model was better in predicting substrate removal rate and both with a precision of between R2 (0.9008-0.9988). Microbial communities examined indicated the abundance of genera, following the biosorbent addition, while RSB and BGC had no negative effect on the bioreactor's performance and bacterial community structure of biomass. Proteobacteria and Bacteroidetes were abundant in BEAS. While the GEAS achieved higher COD and phenol removal due to high Nitrosomonas, Nitrospira, Comamonas, Methanomethylovorans and Acinetobacter abundance in the activated sludge. Thus, this study demonstrated that the combination of biosorption and activated sludge processes could be promising, highly efficient, and most economical for AIBW treatment, without jeopardising the elimination of pollutants or the development of microbial communities.
    MeSH terms: Sewage/chemistry; Waste Disposal, Fluid/methods; Bioreactors/microbiology; Phenol; Biological Oxygen Demand Analysis; Waste Water*; Microbiota*
  14. Ing SK, Lee GWC, Leong TS, Lee YH, Lau GYL, Yusof NN, et al.
    Clin Med (Lond), 2023 Jul;23(4):414-416.
    PMID: 37524430 DOI: 10.7861/clinmed.2023-0171
    Tuberculosis-associated hemophagocytic lymphohistiocytosis (TB-HLH) is a rare and life-threatening complication of tuberculosis infection. Early recognition and treatment of TB-HLH is crucial for improving outcomes. Treatment typically involves a combination of antituberculosis therapy and immunosuppressive therapy to control the immune system's overreaction. In this report, we present the case of a 53-year-old ambulance driver who was diagnosed with TB-HLH. His CT scan revealed splenic abscesses, hepatomegaly and bilateral lung consolidation. He subsequently developed multiorgan failure, including acute respiratory distress syndrome (ARDS), transaminitis and bone marrow dysfunction. The clinical course and simultaneous increase in serum ferritin raised the suspicion of HLH. His Hscore was 254, indicating a high probability of hemophagocytic syndrome. TB diagnosis was confirmed by positive endotracheal TB GeneXpert and bone marrow aspiration (BMA) which detected acid-fast bacilli organisms. The patient was promptly started on anti-TB, dexamethasone and IVIG. The patient responded well to treatment and made a full recovery without any lasting complications. This case highlights the importance of promptly recognising HLH and identifying the underlying cause. In critically ill patients, it is crucial not to delay HLH-specific treatment while working up for differential diagnosis.
    MeSH terms: Bone Marrow; Humans; Male; Middle Aged; Mycobacterium tuberculosis*
  15. Pervez MN, Yeo WS, Lin L, Xiong X, Naddeo V, Cai Y
    Sci Rep, 2023 Jul 31;13(1):12363.
    PMID: 37524835 DOI: 10.1038/s41598-023-39528-1
    The typical textile dyeing process calls for a wide range of operational parameters, and it has always been difficult to pinpoint which of these qualities is the most important in dyeing performance. Consequently, this research used a combined design of experiments and machine learning prediction models' method to offer a sustainable and beneficial reactive cotton fabric dyeing process. To be more precise, we built a least square support vector regression (LSSVR) model based on Taguchi's statistical orthogonal design (L27) to predict exhaustion percentage (E%), fixation rate (F%), and total fixation efficiency (T%) and color strength (K/S) in the reactive cotton dyeing process. The model's prediction accuracy was assessed using many measures, including root mean square error (RMSE), mean absolute error (MAE), and the coefficient of determination (R2). Principal component regression (PCR), partial least square regression (PLSR), and fuzzy modelling were some of the other types of regression models used to compare results. Our findings reveal that the LSSVR model greatly outperformed competing models in predicting the E%, F%, T%, and K/S. This is shown by the LSSVR model's much smaller RMSE and MAE values. Overall, it provided the highest possible R2 values, which reached 0.9819.
  16. Bhatt P, Sethi A, Tasgaonkar V, Shroff J, Pendharkar I, Desai A, et al.
    Brain Inform, 2023 Jul 31;10(1):18.
    PMID: 37524933 DOI: 10.1186/s40708-023-00196-6
    Human behaviour reflects cognitive abilities. Human cognition is fundamentally linked to the different experiences or characteristics of consciousness/emotions, such as joy, grief, anger, etc., which assists in effective communication with others. Detection and differentiation between thoughts, feelings, and behaviours are paramount in learning to control our emotions and respond more effectively in stressful circumstances. The ability to perceive, analyse, process, interpret, remember, and retrieve information while making judgments to respond correctly is referred to as Cognitive Behavior. After making a significant mark in emotion analysis, deception detection is one of the key areas to connect human behaviour, mainly in the forensic domain. Detection of lies, deception, malicious intent, abnormal behaviour, emotions, stress, etc., have significant roles in advanced stages of behavioral science. Artificial Intelligence and Machine learning (AI/ML) has helped a great deal in pattern recognition, data extraction and analysis, and interpretations. The goal of using AI and ML in behavioral sciences is to infer human behaviour, mainly for mental health or forensic investigations. The presented work provides an extensive review of the research on cognitive behaviour analysis. A parametric study is presented based on different physical characteristics, emotional behaviours, data collection sensing mechanisms, unimodal and multimodal datasets, modelling AI/ML methods, challenges, and future research directions.
  17. Shah MA, Shitara K, Ajani JA, Bang YJ, Enzinger P, Ilson D, et al.
    Nat Med, 2023 Aug;29(8):2133-2141.
    PMID: 37524953 DOI: 10.1038/s41591-023-02465-7
    There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .
    MeSH terms: Capecitabine/therapeutic use; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; Esophagogastric Junction/pathology; Humans; Claudins/therapeutic use; Antibodies, Monoclonal, Humanized/therapeutic use
  18. Tantavisut S, Ho KY, Arandia EF, Cheng SC, Eiamtanasate S, Jarayabhand R, et al.
    Cureus, 2023 Jun;15(6):e41156.
    PMID: 37525772 DOI: 10.7759/cureus.41156
    INTRODUCTION: Multimodal analgesia is key in the effective management of acute pain. Previous clinical trials have demonstrated good results with the use of a fixed-dose combination (FDC) of tramadol 75 mg and dexketoprofen 25 mg (TRAM/DKP) in acute pain management. However, there is a dearth of real-world evidence on the efficacy and safety of this combination in the management of acute non-surgical pain, especially among Asian patients. The case series reported herein investigates the real-world experiences of physicians and Asian patients with the use of TRAM/DKP FDC in the management of acute non-surgical pain.

    METHODS: Data were collected retrospectively on 11 Asian patients across multiple hospitals who had received a short course of TRAM/DKP FDC for acute non-surgical orthopaedic and non-orthopaedic pain. Data on baseline characteristics, medical history, treatment regimen, clinical outcomes, and patient satisfaction were compiled and shared at a peer-to-peer expert meeting in October 2022.

    RESULTS: All patients experienced a reduction in pain intensity and were very satisfied with pain management, with a mean satisfaction score of 4.3/5. Five patients (range: 63-74 years) experienced mild adverse events, including nausea, vomiting, and dizziness, which resolved with no need for additional treatment in the majority of cases. No serious adverse events were recorded.

    CONCLUSION: Asian patients with acute non-surgical orthopaedic and non-orthopaedic pain achieved good pain control with TRAM/DKP FDC. The regimen was well tolerated, and patients reported high levels of satisfaction with the outcomes, indicating that TRAM/DKP FDC is an effective choice for the control of acute non-surgical pain in Asian patients.

  19. Seluarize G, Khairudin MN, Ismail F
    Cureus, 2023 Jun;15(6):e41169.
    PMID: 37525815 DOI: 10.7759/cureus.41169
    Age-related macular degeneration (ARMD) is a group of age-related changes in the macula that can be potentially vision-threatening. In the current era, there are options for treatment modalities that aim to preserve a patient's vision. Poor vision not only serves as a significant factor in halting the elderly population from their daily activities, but it may also result in frequent falls, depression, and impairment of the ability to carry out activities of daily living. We would like to highlight in this clinical presentation simple tools for assessing the severity of disease and the importance of early detection of these patients.
  20. Alruwaili M, Jarrar B, Jarrar Q, Alruwaili M, Goh KW, Moshawih S, et al.
    Front Biosci (Landmark Ed), 2023 Jul 13;28(7):137.
    PMID: 37525906 DOI: 10.31083/j.fbl2807137
    BACKGROUND: Hydroxychloroquine (HCQ) toxicity can adversely affect vital organs, cause pathologic ocular damage, and can have direct cardiovascular effects. This study aims to identify the biochemical, hematological, and histological alterations of the vital organs associated with the effects of HCQ.

    METHODS: Male albino rats were exposed to the equivalent of HCQ therapeutic doses given to human patients being affected by malaria, lupus erythematosus, and COVID-19. The animal blood samples were subjected to hematological analysis, biochemical analysis, liver function tests, kidney function tests, and cardiac biomarkers. Liver, kidney, heart, spleen, and testis biopsies were subjected to histological examination.

    RESULTS: HCQ significantly lowered the values of erythrocytes, hemoglobin, hematocrit, platelets, leucocytes, and lymphocytes but significantly increased the values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, alkaline phosphatase, lactate dehydrogenase, cholesterol, and chlorine ions. The renal tissues of HCQ-treated animals demonstrated glomerular fragmentation, partial atrophy degeneration, renal tubules hydropic degeneration, hyaline cast formation, and interstitial edema formation. Additionally, the heart exhibited myofiber necrosis, myolysis, wavy appearance, disorganization, and disarray. The testicular tissues also demonstrated spermatocyte degeneration, spermatogenic cell sloughing, testicular interstitial edema, and occasional spermatogenic arrest. Additionally, the spleen showed a decrease in the number and size of the white pulp follicles, a decrease in the number of apoptotic activity, and a decline in the number of T-rich cells. However, the red pulp demonstrated a diffuse decline in B rich-lymphocytes and macrophages. The liver was also the least affected but showed Kupffer cell hyperplasia and occasional hepatocyte dysplasia.

    CONCLUSIONS: The results indicate that chronic exposure to HCQ could alter the structures and functions of the vital organs.

    MeSH terms: Animals; Humans; Liver/pathology; Male; Necrosis/pathology; Rats
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