Prevalence and Association of Sarcopenia with Mortality in Patients with Head and Neck Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: The objective of this meta-analysis was to assess the association of sarcopenia defined on computed tomography (CT) head and neck with survival in head and neck cancer patients. METHODS: Following a PROSPERO-registered protocol, two blinded reviewers extracted data and evaluated the quality of the included studies using the Quality In Prognostic Studies (QUIPS) tool, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. A meta-analysis was conducted using maximally adjusted hazard ratios (HRs) with the random-effects model. Heterogeneity was measured using the I2 statistic and was investigated using meta-regression and subgroup analyses where appropriate. RESULTS: From 37 studies (11,181 participants), sarcopenia was associated with poorer overall survival (HR 2.11, 95% confidence interval [CI] 1.81-2.45; p < 0.01), disease-free survival (HR 1.76, 95% CI 1.38-2.24; p < 0.01), disease-specific survival (HR 2.65, 95% CI 1.80-3.90; p < 0.01), progression-free survival (HR 2.24, 95% CI 1.21-4.13; p < 0.01) and increased chemotherapy or radiotherapy toxicity (risk ratio 2.28, 95% CI 1.31-3.95; p < 0.01). The observed association between sarcopenia and overall survival remained significant across different locations of cancer, treatment modality, tumor stages and geographical region, and did not differ between univariate and multivariate HRs. Statistically significant correlations were observed between the C3 and L3 cross-sectional area, skeletal muscle mass, and skeletal muscle index. CONCLUSIONS: Among patients with head and neck cancers, CT-defined sarcopenia was consistently associated with poorer survival and greater toxicity.

A Prospective Study of Bladder Function Following Endometriosis Surgery With Up to Eight years Follow-up.

STUDY OBJECTIVE: To assess long-term urinary function for women having laparoscopic surgery for endometriosis. DESIGN: Institutional Review Board-approved nested cohort study within a larger randomized controlled trial assessing urinary function following any benign laparoscopy for gynecological presentations. SETTING: Two tertiary-level university-affiliated hospitals. PATIENTS: Women with histologically confirmed endometriosis within the randomized controlled trial between April 2012 and November 2019, where baseline urinary function was determined. INTERVENTIONS: Women with histologically confirmed endometriosis were contacted between February and October 2020, and urinary function was re-assessed. MEASUREMENTS AND MAIN RESULTS: Urinary function was assessed using validated questionnaires across the domains of filling, voiding, incontinence, and quality of life determined distant from surgery. Higher scores correlated with a greater severity of symptoms. From 518/711 (72.9%) women with histologically confirmed endometriosis, 289/518 (55.8%) consented to the nested study. At a mean of 50 months (range 12-103 months) post-operatively, 35 participants (12.1%) had sought treatment for bladder symptoms, and 81 participants (28.0%) reported at least one urinary tract infection since their index surgery. There was a significant worsening of symptoms for filling, voiding, incontinence, and quality of life pre-operative to post-operatively (2.27 vs 3.32, 0.93 vs 2.02, 1.06 vs 2.32, 0.83 vs 2.13 respectively, p <.001). There was no statistically significant difference in urinary questionnaire scores in participants with and without uterovesical endometriosis. There was no statistically significant difference in any parameter when comparing any revised American Society of Reproductive Medicine (rASM) stage of endometriosis. Participants who had post-operative urinary retention reported a higher mean voiding score than those who did not (3.24 vs 1.94, p = .017), while participants with post-operative urinary tract infection reported a higher mean frequency score than those who did not (5.17 vs 3.24, p = .016). CONCLUSION: This study suggests a decline in urinary function over time following laparoscopic surgery for endometriosis that is not dependent on the severity or location of the disease.

Immediate versus delayed urinary catheter removal following non-hysterectomy benign gynaecological laparoscopy: a randomised trial.

OBJECTIVE: To compare rates of urinary retention and postoperative urinary tract infection between women with immediate versus women with delayed removal of indwelling catheter following benign non-hysterectomy gynaecological laparoscopic surgery. DESIGN: This randomised clinical trial was conducted between February 2012 and December 2019, with follow-up to 6 weeks. SETTING: Two university-affiliated teaching hospitals in Sydney, Australia. POPULATION: Study participants were 693 women aged 18 years or over, undergoing non-hysterectomy laparoscopy for benign gynaecological conditions, excluding pelvic floor or concomitant bowel surgery. METHODS: Three hundred and fifty-five participants were randomised to immediate removal of urinary catheter and 338 participants were randomised to delayed removal of urinary catheter. MAIN OUTCOME MEASURES: The co-primary outcomes were urinary retention and urinary tract infection. Secondary outcomes included hospital readmission, analgesia requirements, duration of hospitalisation and validated bladder function questionnaires. RESULTS: Urinary retention was higher after immediate compared with delayed removal of the urinary catheter (8.2% vs 4.2%, RR 1.8, 95% CI 1.0-3.0, p = 0.04). Although urinary tract infection was 7.2% following delayed removal of the urinary catheter and 4.7% following immediate removal of the urinary catheter, the difference was not statistically significant (RR 0.7, 95% CI 0.3-1.2, p = 0.2). CONCLUSIONS: There is an increased risk of urinary retention with the immediate compared with the delayed removal of the urinary catheter following benign non-hysterectomy gynaecological laparoscopic surgery. The difference in urinary tract infection was not significant. There is 1/12 risk of re-catheterisation after immediate urinary catheter removal. It is important to ensure that patients report normal voiding and emptying prior to discharge, to reduce the need for readmission for the management of urinary retention.

A Double-blinded, Randomized, Placebo-controlled Trial of Antibiotic Prophylaxis in Elective Non-hysterectomy Laparoscopic Surgery for Benign Gynecologic Conditions: A Pilot Study.

STUDY OBJECTIVE: To determine the feasibility of a double-blinded randomized, placebo-controlled study in determining the efficacy of antibiotic prophylaxis in preventing postoperative infections (POIs) in elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions. DESIGN: Double-blinded, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary referral hospital in Sydney, Australia. PATIENTS: Women older than 18 years undergoing elective nonhysterectomy laparoscopic procedures for benign gynecologic conditions were eligible for the study and approached. INTERVENTIONS: Before surgery, participants were randomized to receive either 2-g cephazolin or placebo (10-mL normal saline) administered by the anesthetist. Participants and other research staff were blinded to group allocation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was study feasibility measured by recruitment rates, compliance rates of drug administration, compliance rates of delivery, maintenance of double blinding, and follow-up rates. Secondary outcomes included rate of POIs, length of hospitalization, readmission to hospital, unscheduled presentations to healthcare facilities, and antibiotic-related reactions. Between February 2019 and March 2021, 170 patients were approached with 117 participants (68.8%) recruited and randomized. The study had a high compliance rate of trial drug delivery (95.7%) and a high follow-up rate (99.1%). CONCLUSION: This pilot study has demonstrated feasibility of a large-scale study with a recruitment rate of 68% of patients approached and excellent trial drug delivery and follow-up rates. As anticipated, it is underpowered for identifying clinically significant findings for POI rates. A large-scale study is appropriate and essential to determine the health-related risks of antibiotic prophylaxis with an emphasis on antimicrobial stewardship. The sample size for a large-scale study is 1678 participants based on infection rates in this pilot study.

A review of gynaecological surgical practices for trainees and certified specialists in Australia by volume using MBS and AIHW databases.

BACKGROUND: There is a finite volume of surgery performed annually by trainees and certified specialists alike. The detailed assessment of this surgical substrate is important, since it guides true exposure in gynaecological surgical training and practice after fellowship. AIMS: This study quantifies the volume and profile of major gynaecological surgical procedures performed in Australia within a specified five-year period and discusses the implications for training and practice. MATERIALS AND METHODS: Australian Institute of Health and Welfare data were examined to quantify the total number of major gynaecological procedures performed between 2013 and 2018. Medicare data were analysed to quantify the number of billed procedures. These data were compared with published Australian RANZCOG trainees and operative gynaecologists, to estimate the potential annual average exposure for each procedure. RESULTS: Major open, laparoscopic and vaginal surgeries constitute less than 27% of the 600 000 gynaecological procedures performed annually in Australia. Most major gynaecological surgeries are performed at rates lower than 12 cases per year for both trainees and specialists. Over the study period, laparotomies, vaginal hysterectomies and continence procedures decreased, and operative laparoscopies and laparoscopic hysterectomies increased. CONCLUSIONS: The volume of available major gynaecological procedures in Australia may not allow sufficient exposure for optimal training and practice for all trainees and specialists in operative gynaecology. This shortfall may compromise the ability to obtain and maintain proficiency in some core gynaecological operative procedures.

Computer-assisted EEG diagnostic review for idiopathic generalized epilepsy.

Epilepsy diagnosis can be costly, time-consuming, and not uncommonly inaccurate. The reference standard diagnostic monitoring is continuous video-electroencephalography (EEG) monitoring, ideally capturing all events or concordant interictal discharges. Automating EEG data review would save time and resources, thus enabling more people to receive reference standard monitoring and also potentially heralding a more quantitative approach to therapeutic outcomes. There is substantial research into the automated detection of seizures and epileptic activity from EEG. However, automated detection software is not widely used in the clinic, and despite numerous published algorithms, few methods have regulatory approval for detecting epileptic activity from EEG. This study reports on a deep learning algorithm for computer-assisted EEG review. Deep convolutional neural networks were trained to detect epileptic discharges using a preexisting dataset of over 6000 labelled events in a cohort of 103 patients with idiopathic generalized epilepsy (IGE). Patients underwent 24-hour ambulatory outpatient EEG, and all data were curated and confirmed independently by two epilepsy specialists (Seneviratne et al., 2016). The resulting automated detection algorithm was then used to review diagnostic scalp EEG for seven patients (four with IGE and three with events mimicking seizures) to validate performance in a clinical setting. The automated detection algorithm showed state-of-the-art performance for detecting epileptic activity from clinical EEG, with mean sensitivity of >95% and corresponding mean false positive rate of 1 detection per minute. Importantly, diagnostic case studies showed that the automated detection algorithm reduced human review time by 80%-99%, without compromising event detection or diagnostic accuracy. The presented results demonstrate that computer-assisted review can increase the speed and accuracy of EEG assessment and has the potential to greatly improve therapeutic outcomes. This article is part of the Special Issue "NEWroscience 2018".

Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial.

Importance: Postmenopausal vaginal symptoms are common and frequently detrimental to a woman's quality of life. Fractional carbon dioxide vaginal laser is increasingly offered as a treatment, but the efficacy remains unproven. Objective: To determine the efficacy of fractional carbon dioxide laser for treatment of vaginal symptoms associated with menopause. Design, Setting, and Participants: A double-blind, randomized, sham-controlled trial with 12-month follow-up was undertaken at a single tertiary referral hospital in Sydney, Australia. Enrollment commenced on September 19, 2016, with final follow-up on June 30, 2020. Participants were postmenopausal women with vaginal symptoms substantive enough to seek medical treatment. Of 232 participants approached, 85 were randomized. Interventions: Three treatments using a fractional microablative carbon dioxide laser system performed 4 to 8 weeks apart, with 43 women randomized to the laser group and 42 to the sham group. Main Outcomes and Measures: The co-primary outcomes were symptom severity assessed using a visual analog scale (VAS; range, 0-100; 0 indicates no symptoms and 100 indicates the most severe symptoms) and the Vulvovaginal Symptom Questionnaire (VSQ; range, 0-20; 0 indicates no symptoms and 20 indicates the most severe symptoms) at 12 months. The minimal clinically important difference was specified as a 50% decrease in both VAS and VSQ severity scores. There were 5 prespecified secondary outcomes, including quality of life (range, 0-100; higher scores indicate better quality of life), the Vaginal Health Index Score (range, 5-25; higher scores indicate better health), and vaginal histology (premenopausal or postmenopausal status). Results: Of 85 randomized participants (mean [SD] age, 57 [8] years), 78 (91.7%) completed the 12-month follow-up. From baseline to 12 months, there was no significant difference between the carbon dioxide laser group and the sham group in change in symptom severity (VAS score for overall vaginal symptoms: -17.2 vs -26.6; difference, 9.4 [95% CI, -28.6 to 47.5]; VAS score for the most severe symptom: -24.5 vs -20.4; difference -4.1 [95% CI, -32.5 to 24.3]; VSQ score: -3.1 vs -1.6; difference, -1.5 [95% CI, -5.9 to 3.0]). There were no significant differences between the laser and sham group in the mean quality of life score (6.3 vs 1.4; difference, 4.8 [95% CI, -3.9 to 13.5]) and Vaginal Health Index Score (0.9 vs 1.3; difference, -0.4 [95% CI, -4.3 to 3.6]) or in histological comparisons between laser and sham treatment groups. There were 16 adverse events in the laser group and 17 in the sham group, including vaginal pain/discomfort (44% vs 68%), spotting, discharge, and lower urinary tract symptoms. No severe adverse events were reported in either group. Conclusions and Relevance: Among women with postmenopausal vaginal symptoms, treatment with fractional carbon dioxide laser vs sham treatment did not significantly improve vaginal symptoms after 12 months. Trial Registration: Australian and New Zealand Clinical Trials Registry: ACTRN12616001403426.

Identification of Phytoconstituents in Leea indica (Burm. F.) Merr. Leaves by High Performance Liquid Chromatography Micro Time-of-Flight Mass Spectrometry.

Leea indica (Vitaceae) is a Southeast Asian medicinal plant. In this study, an ethyl acetate fraction of L. indica leaves was studied for its phytoconstituents using high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-microTOF-Q-MS/MS) analysis. A total of 31 compounds of different classes, including benzoic acid derivatives, phenolics, flavonoids, catechins, dihydrochalcones, coumarins, megastigmanes, and oxylipins were identified using LC-MS/MS. Among them, six compounds including gallic acid, methyl gallate, (-)-epigallocatechin-3-O-gallate, myricetin-3-O-rhamnoside, quercetin-3-O-rhamnoside, and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-ß-d-glucopyranoside were isolated and identified by NMR analysis. The LC-MS/MS analysis led to the tentative identification of three novel dihydrochalcones namely 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-rutinoside, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-glucosylpentoside and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-(3″-O-galloyl)-ß-d-glucopyranoside. The structural identification of novel dihydrochalcones was based on the basic skeleton of the isolated dihydrochalcone, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-ß-d-glucopyranoside and characteristic LC-MS/MS fragmentation patterns. This is the first comprehensive analysis for the identification of compounds from L. indica using LC-MS. A total 24 compounds including three new dihydrochalcones were identified for the first time from the genus Leea.

Ethnic Differences in the Safety and Efficacy of Tenecteplase Versus Alteplase for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Tenecteplase is a thrombolytic agent with pharmacological advantages over alteplase and has been shown to be noninferior to alteplase for acute ischemic stroke in randomized trials. However, evidence pertaining to the safety and efficacy of tenecteplase in patients from different ethnic groups is lacking. The aim of this systematic review and metaanalysis was to investigate ethnicity-specific differences in the safety and efficacy of tenecteplase versus alteplase in patients with acute ischemic stroke. METHODS: Following an International Prospective Register of Systematic Reviews (PROSPERO)- registered protocol (CRD42023475038), three authors conducted a systematic review of the PubMed/MEDLINE, Embase, Cochrane Library, and CINAHL databases for articles comparing the use of tenecteplase with any thrombolytic agent in patients with acute ischemic stroke up to November 20, 2023. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Two independent authors extracted data onto a standardized data collection sheet. A pairwise meta-analysis was conducted in risk ratios (RR). RESULTS: From 34 studies (59,601 participants), the rate of complete recanalization was significantly higher (P<0.01) in Asian (RR: 1.91, 95% confidence interval [CI]: 1.30 to 2.80) versus Caucasian patients (RR: 0.99, 95% CI: 0.87 to 1.14). However, Asian patients (RR: 1.18, 95% CI: 0.87 to 1.62) had significantly higher (P=0.01) rates of mortality compared with Caucasian patients (RR: 1.10, 95% CI: 1.00 to 1.22). Caucasian patients were also more likely to attain a modified Rankin Scale (mRS) score of 0 to 2 at follow-up (RR: 1.14, 95% CI, 1.10 to 1.19) compared with Asian (RR: 1.00, 95% CI, 0.95 to 1.05) patients. There was no significant difference in the rate of symptomatic intracranial hemorrhage (P=0.20) and any intracranial hemorrhage (P=0.83) between Asian and Caucasian patients. CONCLUSION: Tenecteplase was associated with significantly higher rates of complete recanalization in Asian patients compared with Caucasian patients. However, tenecteplase was associated with higher rates of mortality and lower rates of mRS 0 to 2 in Asian patients compared with Caucasian patients. It may be beneficial to study the variations in response to tenecteplase among patients of different ethnic groups in large prospective cohort studies.

Association of head and neck CT-derived sarcopenia with mortality and adverse outcomes: A systematic review.

BACKGROUND: There is growing interest in the association of CT-assessed sarcopenia with adverse outcomes in non-oncological settings. PURPOSE: The aim of this systematic review is to summarize existing literature on the prognostic implications of CT-assessed sarcopenia in non-oncological patients. MATERIALS AND METHODS: Three independent authors searched Medline/PubMed, Embase and Cochrane Library up to 30 December 2023 for observational studies that reported the presence of sarcopenia defined on CT head and neck in association with mortality estimates and other adverse outcomes, in non-oncological patients. The quality of included studies were assessed using the Quality of Prognostic Studies tool. RESULTS: Overall, 15 studies (3829 participants) were included. Nine studies were at low risk of bias, and six were at moderate risk of bias. Patient populations included those admitted for trauma or treatment of intracranial aneurysms, ischemic stroke, transient ischemic attack, and intracranial stenosis. Sarcopenia was associated with increased 30-day to 2-year mortality in inpatients and patients undergoing carotid endarterectomy or mechanical thrombectomy for acute ischemic stroke. Sarcopenia was also associated with poorer neurological and functional outcomes, increased likelihood of admission to long-term care facilities, and longer duration of hospital stays. The observed associations of sarcopenia with adverse outcomes remained similar across different imaging modalities and methods for quantifying sarcopenia. CONCLUSION: CT-assessed sarcopenia was associated with increased mortality and poorer outcomes across diverse patient populations. Measurement and early identification of sarcopenia in vulnerable patients allows for enhanced prognostication, and focused allocation of resources to mitigate adverse outcomes.

Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury.

Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI. Methods: We have applied a three-dose paradigm of 10µg/40µl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging. Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment. Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.

Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury.

Background: Links between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI. Methods: We have applied a three-dose paradigm of 10µg/40µl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging. Results: Three doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment. Conclusions: Overall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.

Effects of Leea indica leaf extracts and its phytoconstituents on natural killer cell-mediated cytotoxicity in human ovarian cancer.

BACKGROUND: The rich biodiversity of medicinal plants and their importance as sources of novel therapeutics and lead compounds warrant further research. Despite advances in debulking surgery and chemotherapy, the risks of recurrence of ovarian cancer and resistance to therapy are significant and the clinical outcomes of ovarian cancer remain poor or even incurable. OBJECTIVE: This study aims to investigate the effects of leaf extracts from a medicinal plant Leea indica and its selected phytoconstituents on human ovarian cancer cells and in combination with oxaliplatin and natural killer (NK) cells. METHODS: Fresh, healthy leaves of L. indica were harvested and extracted in 70% methanol by maceration. The crude extract was partitioned with n-hexane, dichloromethane and ethyl acetate. Selected extracts and compounds were analyzed for their effects on cell viability of human ovarian cancer cells, NK cell cytotoxicity, and stress ligands expression for NK cell receptors. They were also evaluated for their effects on TNF-α and IL-1ß production by enzyme-linked immunosorbent assay in lipopolysaccharide-stimulated human U937 macrophages. RESULTS: Leaf extracts of L. indica increased the susceptibility of human ovarian tumor cells to NK cell-mediated cytotoxicity. Treatment of cancer cells with methyl gallate but not gallic acid upregulated the expression of stress ligands. Tumor cells pretreated with combination of methyl gallate and low concentration of oxaliplatin displayed increased levels of stress ligands expression and concomitantly enhanced susceptibility to NK cell-mediated cytolysis. Further, NK cells completely abrogated the growth of methyl gallate-pretreated ovarian cancer cells. The leaf extracts suppressed TNF-α and IL-1ß production in human U937 macrophages. Methyl gallate was more potent than gallic acid in down-regulating these cytokine levels. CONCLUSIONS: We demonstrated for the first time that leaf extracts of L. indica and its phytoconstituent methyl gallate enhanced the susceptibility of ovarian tumor cells to NK cell cytolysis. These results suggest that the combined effect of methyl gallate, oxaliplatin and NK cells in ovarian cancer cells warrants further investigation, for example for refractory ovarian cancer. Our work is a step towards better scientific understanding of the traditional anticancer use of L. indica.

Predictors of Mortality in Home Health Care Service: Data from Saudi Arabia.

Objective: This study aimed to 1) report the prevalence of chronic conditions among Saudi people receiving long-term home health care (HHC) services, 2) identify the predictors of mortality among individuals receiving long-term HHC services, and 3) study the association between frailty and poor health outcomes among HHC users. Design: Retrospective cross-sectional descriptive study. Setting and Participants: A total of 555 participants were recruited from HHC services at King Saud University Medical City (KSUMC), Riyadh, Saudi Arabia. We collected the data from electronic health records (EHR), patient charts, and caregiver interviews for 555 participants included in HHC program from the year 2019 to 2022. Methods: Only individuals fulfilling the HHC program's eligibility criteria were included to the study. A total of 555 participants were included in the analysis. We assessed the functional performance by the Katz activity of daily living and Bristol Activity of Daily Living Scale (BADLS). A trained health care provider assessed frailty using the Clinical Frailty Scale (CFS). We calculated the means and frequency to describe the prevalence of chronic conditions and variables of interest. A Chi-square test or independent-samples t-test was run to determine if there were differences between the alive and deceased individuals. A binary logistic regression model was performed to predict mortality of HHC service recipients. Results: The mean age for deceased individuals in HHC was 78.3 years. Over twenty percent of individuals receiving HHC services were readmitted to the hospital. We found that the strongest predictors for mortality were pressure ulcers with an odds ratio of 3.75 and p-value of <0.0001, and the Clinical Frailty Scale, which had an odds ratio of 1.69 and p-value of 0.002, using multivariate regression analysis. Conclusions and Implications: In conclusion, our study found that pressure ulcers and frailty are the strongest predictors of mortality for individuals receiving home health care services.

Compensation of retinal nerve fibre layer thickness as assessed using optical coherence tomography based on anatomical confounders.

BACKGROUND/AIMS: To compensate the retinal nerve fibre layer (RNFL) thickness assessed by spectral-domain optical coherence tomography (SD-OCT) for anatomical confounders. METHODS: The Singapore Epidemiology of Eye Diseases is a population-based study, where 2698 eyes (1076 Chinese, 704 Malays and 918 Indians) with high-quality SD-OCT images from individuals without eye diseases were identified. Optic disc and macular cube scans were registered to determine the distance between fovea and optic disc centres (fovea distance) and their respective angle (fovea angle). Retinal vessels were segmented in the projection images and used to calculate the circumpapillary retinal vessel density profile. Compensated RNFL thickness was generated based on optic disc (ratio, orientation and area), fovea (distance and angle), retinal vessel density, refractive error and age. Linear regression models were used to investigate the effects of clinical factors on RNFL thickness. RESULTS: Retinal vessel density reduced significantly with increasing age (1487±214 µm in 40-49, 1458±208 µm in 50-59, 1429±223 µm in 60-69 and 1415±233 µm in ≥70). Compensation reduced the variability of RNFL thickness, where the effect was greatest for Chinese (10.9%; p<0.001), followed by Malays (6.6%; p=0.075) and then Indians (4.3%; p=0.192). Compensation reduced the age-related RNFL decline by 55% in all participants (ß=-3.32 µm vs ß=-1.50 µm/10 years; p<0.001). Nearly 62% of the individuals who were initially classified as having abnormally thin RNFL (outside the 99% normal limits) were later reclassified as having normal RNFL. CONCLUSIONS: RNFL thickness compensated for anatomical parameters reduced the variability of measurements and may improve glaucoma detection, which needs to be confirmed in future studies.

Evaluation of anti-proliferative activity of medicinal plants used in Asian Traditional Medicine to treat cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: The extensive biodiversity of plants in Southeast Asia and inadequate research hitherto warrant a continued investigation into medicinal plants. On the basis of a careful review of fresh medicinal plant usage to treat cancer from previous ethnobotanical interviews in Singapore and from the traditional uses of the indigenous plants, fresh leaves of seven locally grown medicinal plant species were evaluated for anti-proliferative activity. AIM OF THE STUDY: To evaluate the anti-proliferative activity of local medicinal plant species Clausena lansium Skeels, Clinacanthus nutans (Burm. f.) Lindau, Leea indica (Burm. f.) Merr., Pereskia bleo (Kunth) DC., Strobilanthes crispus (L.) Blume, Vernonia amygdalina Delile and Vitex trifolia L. MATERIALS AND METHOD: Fresh, healthy and mature leaves of the seven medicinal plants were harvested from various locations in Singapore and Malaysia for Soxhlet, ultrasonication and maceration extractions in three different solvents (water, ethanol and methanol). Cell proliferation assay using water soluble tetrazolium salt (WST-1) assay was performed on twelve human cancer cell lines derived from breast (MDA-MB-231, T47D), cervical (C33A), colon (HCT116), leukemia (U937), liver (HepG2, SNU-182, SNU-449), ovarian (OVCAR-5, PA-1, SK-OV-3) and uterine (MES-SA/DX5) cancer. RESULTS: A total of 37 fresh leaf extracts from seven medicinal plants were evaluated for their anti-tumour activities in twelve human cancer cell lines. Of these, the extracts of C. lansium, L. indica, P. bleo, S. crispus, V. amygdalina and V. trifolia exhibited promising anti-proliferative activity against multiple cancer cell lines. Further investigation of selected promising leaf extracts indicated that maceration methanolic extract of L. indica was most effective overall against majority of the cancer cell lines, with best IC50 values of 31.5 ±â€¯11.4 µg/mL, 37.5 ±â€¯0.7 µg/mL and 43.0 ±â€¯6.2 µg/mL in cervical C33A, liver SNU-449, and ovarian PA-1 cancer cell lines, respectively. CONCLUSION: The results of this study provide new scientific evidence for the traditional use of local medicinal plant species C. lansium, L . indica, P. bleo, S. crispus, V. amygdalina and V. trifolia in cancer treatment. These results highlight the importance of the upkeep of these indigenous plants in modern society and their relevance as resources for drug discovery.

Diabetic Retinopathy in the Asia-Pacific.

Diabetic retinopathy (DR), the most common complication of diabetes mellitus, is the leading cause of new cases of blindness in middle-aged and elderly in the Asia-Pacific. It has been estimated that 51% of all those with blindness due to DR globally (n = 424,400) and 56% of those with visual impairment due to DR (2.1 million) come from the Asia-Pacific. Prevalence of DR among those with diabetes ranged from 10% in India to 43% in Indonesia within the Asia-Pacific. Awareness of DR among persons with diabetes ranged from 28% to 84%. Most common modifiable risk factors for DR in the Asia-Pacific were hyperglycemia, blood pressure, dyslipidemia, and obesity. Implementation of systematic screening programs for DR and advancement in telemedicine screening methods have increased patient coverage and cost-effectiveness, though there are still numerous factors impeding screening uptake in the low-middle income regions of the Asia-Pacific. Management and treatment of DR in the Asia-Pacific is mainly limited to traditional laser retinopexy, but it is suboptimal despite new clinical approaches such as use of intravitreal anti.vascular endothelial growth factor and steroids due to limited resources. Further research and data are required to structure a more cost-effective public healthcare program and more awareness-building initiatives to increase the effectiveness of DR screening programs.