Use of sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus and multiple cardiovascular risk factors: An Asian perspective and expert recommendations.

Diabetes mellitus in Asia accounts for more than half of the global prevalence. There is a high prevalence of cardiovascular disease (CVD) in the region among people with type 2 diabetes mellitus (T2DM) and it is often associated with multiple risk factors including hypertension, renal disease and obesity. The early onset of T2DM and the eventual long disease duration portends an increasing proportion of the population to premature CVD. In addition to lowering blood glucose, sodium-glucose co-transporter-2 (SGLT-2) inhibitors exert favourable effects on multiple risk factors (including blood pressure, body weight and renal function) and provide an opportunity to reduce the risk of CVD in patients with T2DM. In this article, we consolidated the existing literature on SGLT-2 inhibitor use in Asian patients with T2DM and established contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, published data from clinical trials in the Asian population (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin, luseogliflozin and tofogliflozin), CVD outcomes trials (EMPAREG-OUTCOME, CANVAS and DECLARE-TIMI 58) and real-world evidence studies (CVD-REAL, EASEL, CVD-REAL 2 and OBSERVE-4D). A series of clinical recommendations on the use of SGLT-2 inhibitors in Asian patients with T2DM was deliberated among experts with multiple rounds of review and voting. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for the primary prevention of heart failure hospitalization and secondary prevention of CVD in patients with T2DM, and should be considered early on in the treatment algorithm for patients with multiple risk factors, or those with established CVD.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

Engineering the Structural and Electronic Phases of MoTe2 through W Substitution.

MoTe2 is an exfoliable transition metal dichalcogenide (TMD) that crystallizes in three symmetries: the semiconducting trigonal-prismatic 2H- or α-phase, the semimetallic and monoclinic 1T'- or ß-phase, and the semimetallic orthorhombic γ-structure. The 2H-phase displays a band gap of ∼1 eV making it appealing for flexible and transparent optoelectronics. The γ-phase is predicted to possess unique topological properties that might lead to topologically protected nondissipative transport channels. Recently, it was argued that it is possible to locally induce phase-transformations in TMDs, through chemical doping, local heating, or electric-field to achieve ohmic contacts or to induce useful functionalities such as electronic phase-change memory elements. The combination of semiconducting and topological elements based upon the same compound might produce a new generation of high performance, low dissipation optoelectronic elements. Here, we show that it is possible to engineer the phases of MoTe2 through W substitution by unveiling the phase-diagram of the Mo1-xWxTe2 solid solution, which displays a semiconducting to semimetallic transition as a function of x. We find that a small critical W concentration xc ∼ 8% stabilizes the γ-phase at room temperature. This suggests that crystals with x close to xc might be particularly susceptible to phase transformations induced by an external perturbation, for example, an electric field. Photoemission spectroscopy, indicates that the γ-phase possesses a Fermi surface akin to that of WTe2.

Highly Efficient Rh(I) Homo- and Heterogeneous Catalysts for C-N Couplings via Hydrogen Borrowing.

Rhodium(I) complexes were explored as catalysts for the hydrogen borrowing reactions of amines and alcohols. Bidentate carbene-triazole ligands were readily synthesized via "click" reactions which allowed a diversity of ligand backbones to be accessed. The catalytic transformations are highly efficient, able to reach completion in under 6 h, and promote C-N bond formation across a range of primary alcohol and amine substrates. Moreover, site-selective catalysis can be achieved using substrates with more than one reactive site. A rhodium(I) complex covalently attached to a carbon black surface was also deployed in the hydrogen borrowing coupling reaction of aniline with benzyl alcohol. This represents the first report of a heterogeneous rhodium catalyst used for hydrogen borrowing.

Advanced cancer patients' attitudes towards, and experiences with, screening for somatic mutations in tumours: a qualitative study.

Somatic mutations in key oncogenes in non-small cell lung cancer (NSCLC) and melanoma are important determinants of tumour sensitivity to targeted therapies. Molecular screening for these predictive biomarkers is routinely used to inform treatment decisions; however, little is known about how best to communicate testing and results to patients. This qualitative study aimed to explore advanced cancer patients' attitudes and experiences regarding somatic tumour screening to identify their information and support needs. Sixteen NSCLC and eight melanoma patients who had undergone screening participated in a semi-structured face-to-face or telephone interview exploring their understanding, views, preferences and needs regarding screening. Interviews were audiotaped, transcribed and analysed for thematic patterns. Participants expressed positive views and unequivocal acceptance of screening, and understood its role in guiding treatment selection. They preferred to receive information verbally through simple, non-technical language from their oncologist with additional take-home materials. Patients were interested in learning about their test results, but wanted discussion to be focused on practical matters relevant to treatment. While receiving their screening results was not considered burdensome, information overload and cancer-related distress were identified as barriers to test comprehension. Patients may benefit from information and decision-related tools to better understand genomic information and adequately support psychosocial outcomes.

Evaluation of the biological differences of canine and human factor VIII in gene delivery: implications in human hemophilia treatment.

The canine is the most important large animal model for testing novel hemophilia A (HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, different biological properties between cFVIII and human FVIII (hFVIII) indicated that the development of novel HA treatment may require careful characterization of non-human FVIII. To investigate whether the data obtained using cFVIII can translate to HA treatment in human, we analyzed the differential biological properties of canine heavy chain (cHC) and light chain (cLC) by comparing with human heavy chain (hHC) and light chain (hLC). The secretion of cHC was 5-30-fold higher than hHC, with or without light chains (LCs). cHC+hLC group exhibited ~18-fold increase in coagulation activity compared with hHC+hLC delivery by recombinant adeno-associated viral vectors. Unlike hHC, the secretion of cHC was independent of LCs. cLC improves the specific activity of FVIII by two- to threefold compared with hLC. Moreover, the cLC, but not cHC, contributes to the higher stability of cFVIII. Our results suggested that the cFVIII expression results in the canine model should be interpreted with caution as the cHC secreted more efficiently than hHC and cLC exhibited a more active and stable phenotype than hLC.

Targeted ultraviolet B phototherapy: definition, clinical indications and limitations.

Targeted ultraviolet B (UVB) phototherapy is defined as UVB radiation applied only to clinically diseased skin, with sparing of adjacent normal skin, unlike conventional phototherapy, which involves irradiation of both diseased and normal skin. Targeted UVB radiation is a relatively new concept, which is now widely available because of advances in technology. Devices developed for targeted UVB phototherapy of the skin include the monochromatic excimer laser and lamp, both of which are now used by dermatologists in developed and developing countries. The aim of this review is to collate data from research studies on targeted phototherapy and to provide a concise description of currently available devices, their clinical indications and therapeutic efficacy. Additionally, potential adverse effects are summarized, and the limitations of these novel devices are highlighted.

Global Registry of Acute Coronary Events (GRACE) Risk Score as a Predictor of In-hospital Mortality for Acute Coronary Syndrome in Trinidad and Tobago.

OBJECTIVE: To determine whether risk stratification using the Global Registry of Acute Coronary Events (GRACE) risk score is a predictor of in-hospital mortality for patients with acute coronary syndrome (ACS) in a multi-ethnic Caribbean population. METHOD: During a six-month period, all patients meeting the GRACE diagnostic criteria for one of the acute coronary syndromes were entered into a prospective single-centre study at one of the major public hospitals in Trinidad and Tobago. Clinical data, the GRACE risk score and in-hospital morbidity and mortality were recorded. Patients were placed into three GRACE risk categories: low, intermediate or high risk. RESULTS: There were 372 patients (mean age 63 years; males 56% and females 44%; hypertension 69%, diabetes mellitus 58%, positive smoking history 43%, previous myocardial infarction 34%), of which 25% were ST-segment elevation myocardial infarction, 56% non-ST-segment myocardial infarction and 19% unstable angina pectoris. In-hospital mortality was 8.3%. There were 35%, 33% and 32% of patients in the high, intermediate and low GRACE risk categories, respectively. The GRACE risk score demonstrated good discrimination (C statistic 0.82, 95% CI 0.755, 0879; p < 0.001) and good calibration (Hosmer-Lemeshow; p = 0.096) for in-hospital mortality in this ACS cohort. CONCLUSION: The GRACE risk score was found to be a reliable predictor of in-hospital mortality in this ACS population and therefore can be used to identify those high-risk patients who may benefit from aggressive management strategies, thereby allowing for more effective use of limited resources.

External validation of the Boston Acute Stroke Imaging Scale and M1-BASIS in thrombolyzed patients.

BACKGROUND AND PURPOSE: Radiological findings play an essential role in therapeutic decision making and prognostication in acute ischemic stroke (AIS). The Boston Acute Stroke Imaging Scale (BASIS) and Middle Cerebral Artery-BASIS (M1-BASIS) methodologies are rapid purely radiological instruments and easily applicable for patients with AIS. We validated these methods in patients with AIS treated with intravenous tissue-type plasminogen activator. METHODS: For BASIS, patients were labeled as having major stroke if there was occlusion of distal internal carotid artery, proximal (both M1 and M2 segments) of middle cerebral artery or the basilar artery, or an Alberta Stroke Program Early CT Score≤7. M1-BASIS differs from BASIS by classifying AIS patients with M2 occlusion as a minor stroke. We evaluated these classification systems for predicting functional outcomes (modified Rankin Scale score 0-1) at 3 months. RESULTS: Two hundred sixty-five consecutive AIS patients treated with intravenous tissue-type plasminogen activator were included. On multivariate analysis, younger age (odds ratio, 1.039, 95% confidence interval, 1.009-1.070; P=0.011), lower National Institutes of Health Stroke Scale score (odds ratio, 1.140; 95% confidence interval, 1.073-1.210; P<0.001), and minor stroke by M1-BASIS (odds ratio, 2.376; 95% confidence interval, 1.047-5.393; P=0.039) were independent predictors of good functional outcome. When compared with National Institutes of Health Stroke Scale, the receiver operating characteristic curves for both BASIS (area under the curve, 0.721) and M1-BASIS (area under the curve, 0.795) correlated well with clinical severity scores. M1-BASIS has an additive effect with the National Institutes of Health Stroke Scale score to predict good outcomes. CONCLUSIONS: The purely radiological M1-BASIS correlates well with the clinical severity of stroke and can be a reliable prognostication tool in thrombolyzed AIS patients. This system might find an important place in the current era of telestroke.

Pilot robotic mastectomy in Singapore (PRoMiSing I) study: first safety and feasibility prospective cohort trial in South East Asia.

BACKGROUND: Robotic mastectomy has been performed worldwide since 2015. The advantages of the robotic approach in nipple-sparing mastectomy have been proven with better visualization and preservation of blood supply to the nipple-areolar complex, with a lower incidence of necrosis. It also allows smaller incisions for both mastectomy and immediate breast reconstruction. To date, no centers in Singapore and Southeast Asia offer robotic mastectomy. We believe that robotic mastectomy is a feasible and safe technique that our population can utilize. OBJECTIVES: This study aimed to ascertain the surgical outcomes and perform a learning curve analysis in patients undergoing robotic mastectomy in a multi-ethnic South East Asian population. METHODS: A single-arm prospective pilot study of eligible patients aged 21-70 years old with early breast cancer or high-risk patients indicated for risk-reducing mastectomy who were eligible and consented to robotic mastectomy were enrolled in this trial from December 22, 2022 to December 15, 2023. RESULTS: A total of 29 consecutive robotic mastectomies were performed. The mean total operative time was 95±10.2 min. The average blood loss was 5.7±1.9 ml, and the average length of stay was 1.05 days. The mean mastectomy specimen weight was 251 g, and there was no conversion to conventional mastectomy in any case. Furthermore, there were no 30-day morbidity or complications in terms of wound infection requiring intervention, flap, and nipple-areolar complex necrosis, and postoperative hematoma/bleeding requiring intervention. CONCLUSION: This study contributes to the current evidence that robotic mastectomy is a safe and feasible option and could prove to be a great alternative to conventional mastectomy. Further prospective trials examining the long-term oncological outcomes of robotic mastectomy will be performed to establish the oncologic safety of this technique in breast cancer treatment.

Urine microbes and predictive metagenomic profiles associate with abnormalities in sperm parameters: implications for male subfertility.

OBJECTIVE: To explore the taxonomic and predicted functional relationship between the urine microbiome and alterations of semen analysis (SA) parameters. DESIGN: Cross-sectional study. SETTING: Academic medical center. PATIENT(S): Men presenting for fertility evaluation or men presenting for vasectomy consultation with proven biological paternity were recruited and stratified on the basis of alterations, or lack thereof, in SA parameters. MAIN OUTCOME MEASURE: Changes in the functional and taxonomic urine microbiome profiles of participants with or without alterations in SA parameters. RESULTS: Seventy-three participants were included in our study. Men with abnormal sperm motility (N = 27) showed a nearly 50-fold higher abundance of Dialister micraerophilus compared with those with normal sperm motility (N = 46). This relationship persisted on canonical correlational analysis (r = 0.439). Men with abnormal sperm concentration (N = 20) showed a lower abundance of Enterococcus faecalis and Staphylococcus aureus, compared with those with normal sperm concentration (N = 53). The urine of participants with impaired sperm motility demonstrated dramatic differences in predictive functional profiles in pathways involved in oxidation-reduction balance and cell longevity. CONCLUSIONS: Our findings underscore differences in the urinary microbiome and abnormalities in semen parameters, especially sperm motility. By incorporating predictive functional profiling, we also highlight possible mechanisms that may drive the observed differences in sperm parameters.

Semen microbiota are dramatically altered in men with abnormal sperm parameters.

There has recently been an explosion of studies implicating the human microbiome in playing a critical role in many disease and wellness states. The etiology of abnormal semen analysis (SA) parameters is not identified in 30% of cases; investigations involving the semen microbiome may bridge this gap. Here, we explore the relationship between the semen microbiome and alterations of sperm parameters. We recruited men presenting for fertility evaluation or vasectomy consultation with proven biological paternity. SA and next generation sequencing was performed. Differential abundance testing using Analysis of composition of Microbiota with Bias Correction (ANCOM-BC) was performed along with canonical correlational analysis for microbial community profiling. Men with abnormal (N = 27) sperm motility showed a higher abundance of Lactobacillus iners compared to those with normal (N = 46) sperm motility (mean proportion 9.4% versus 2.6%, p = 0.046). This relationship persisted on canonical correlational analysis (r = 0.392, p = 0.011). Men with abnormal sperm concentration (N = 20) showed a higher abundance of Pseudomonas stutzeri (2.1% versus 1.0%, p = 0.024) and Pseudomonas fluorescens (0.9% versus 0.7%, p = 0.010), but a lower abundance of Pseudomonas putida (0.5% versus 0.8%, p = 0.020), compared to those with normal sperm concentration (N = 53). Major limitations are related to study design (cross-sectional, observational). Our results suggest that a small group of microorganisms may play a critical role in observed perturbations of SA parameters. Some of these microbes, most notably Lactobacillus iners, have been described extensively within other, fertility-related, contexts, whereas for others, this is the first report where they have potentially been implicated. Advances in our understanding of the semen microbiome may contribute to potentially new therapeutic avenues for correcting impairments in sperm parameters and improving male fertility.

Neutron capture cross section of unstable 63Ni: implications for stellar nucleosynthesis.

The 63Ni(n,γ) cross section has been measured for the first time at the neutron time-of-flight facility n_TOF at CERN from thermal neutron energies up to 200 keV. In total, capture kernels of 12 (new) resonances were determined. Maxwellian averaged cross sections were calculated for thermal energies from kT=5-100 keV with uncertainties around 20%. Stellar model calculations for a 25M⊙ star show that the new data have a significant effect on the s-process production of 63Cu, 64Ni, and 64Zn in massive stars, allowing stronger constraints on the Cu yields from explosive nucleosynthesis in the subsequent supernova.

A two-decade population-based study on the effect of hypertension in the general population with obesity in the United States.

OBJECTIVE: With rising prevalence of hypertension and obesity, the effect of hypertension in obesity remains an important global issue. The prognosis of the US general population with obesity based on hypertension control was examined. METHODS: This study examined participants from the National Health and Nutrition Examination Survey between 1999 and 2018. Individuals with obesity were stratified into no hypertension, controlled hypertension, and uncontrolled hypertension. The study outcome was all-cause mortality. Cox regression of all-cause mortality was adjusted for age, sex, ethnicity, diabetes, and previous myocardial infarction. RESULTS: Of 16,386 individuals with obesity, 53.1% had no hypertension, 24.7% had controlled hypertension, and 22.2% had uncontrolled hypertension. All-cause mortality was significantly higher in uncontrolled hypertension (17.1%), followed by controlled hypertension (14.8%) and no hypertension (4.0%). Uncontrolled hypertension had the highest mortality risk (hazard ratio [HR] 1.34, 95% CI: 1.13-1.59, p = 0.001), followed by controlled hypertension (HR 1.21, 95% CI: 1.10-1.34, p < 0.001), compared with no hypertension after adjustment. The excess mortality trend was more pronounced in females, those with diabetes, and those older than age 65 years. CONCLUSIONS: The incremental mortality risk in controlled and uncontrolled hypertension, compared with the normotensive counterparts, irrespective of sex, age, and diabetes status, urges health care providers to optimize hypertension control and advocate weight loss to achieve better outcomes in obesity.

Global computer-assisted appraisal of osteoporosis risk in Asian women: an innovative study.

AIMS AND OBJECTIVE: To develop a computer-assisted appraisal system of osteoporosis that can predict osteoporosis health risk in community-dwelling women and to use it in an empirical analysis of the risk in Asian women. BACKGROUND: As the literature indicates, health risk assessment tools are generally applied in clinical practice for patient diagnosis. However, few studies have explored how to assist community-dwelling women to understand the risk of osteoporosis without invasive data. DESIGN: A longitudinal, evidence-based study. METHOD: The first stage of this study is to establish a system that combines expertise in nursing, medicine and information technology. This part includes information from random samples (n = 700), including data on bone mineral density, osteoporosis risk factors, knowledge, beliefs and behaviour, which are used as the health risk appraisal system database. The second stage is to apply an empirical study. The relative risks of osteoporosis of the participants (n = 300) were determined with the system. The participants that were classified as at-risk were randomly grouped into experimental and control groups. Each group was treated using different nursing intervention methods. RESULTS: The sensitivity and specificity of the analytical tools was 75%. In empirical study, analysis results indicate that the prevalence of osteoporosis was 14.0%. Data indicate that strategic application of multiple nursing interventions can promote osteoporosis prevention knowledge in high-risk women and enhance the effectiveness of preventive action. CONCLUSIONS: The system can also provide people in remote areas or with insufficient medical resources a simple and effective means of managing health risk and implement the idea of self-evaluation and self-caring among community-dwelling women at home to achieve the final goal of early detection and early treatment of osteoporosis. RELEVANCE TO CLINICAL PRACTICE: This study developed a useful approach for providing Asia women with a reliable, valid, convenient and economical self-health management model. Health care professionals can explore the use of advanced information systems and nursing interventions to increase the effectiveness of osteoporosis prevention programmes for women.

One size does not fit all: variations by ethnicity in demographic characteristics of men seeking fertility treatment across North America.

OBJECTIVE: To compare racial differences in male fertility history and treatment. DESIGN: Retrospective review of prospectively collected data. SETTING: North American reproductive urology centers. PATIENT(S): Males undergoing urologist fertility evaluation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Demographic and reproductive Andrology Research Consortium data. RESULT(S): The racial breakdown of 6,462 men was: 51% White, 20% Asian/Indo-Canadian/Indo-American, 6% Black, 1% Indian/Native, <1% Native Hawaiian/Other Pacific Islander, and 21% "Other". White males sought evaluation sooner (3.5 ± 4.7 vs. 3.8 ± 4.2 years), had older partners (33.3 ± 4.9 vs. 32.9 ± 5.2 years), and more had undergone vasectomy (8.4% vs. 2.9%) vs. all other races. Black males were older (38.0 ± 8.1 vs. 36.5 ± 7.4 years), sought fertility evaluation later (4.8 ± 5.1 vs. 3.6 ± 4.4 years), fewer had undergone vasectomy (3.3% vs. 5.9%), and fewer had partners who underwent intrauterine insemination (8.2% vs. 12.6%) compared with all other races. Asian/Indo-Canadian/Indo-American patients were younger (36.1 ± 7.2 vs. 36.7 ± 7.6 years), fewer had undergone vasectomy (1.2% vs. 6.9%), and more had partners who underwent intrauterine insemination (14.2% vs. 11.9%). Indian/Native males sought evaluation later (5.1 ± 6.8 vs. 3.6 ± 4.4 years) and more had undergone vasectomy (13.4% vs. 5.7%). CONCLUSION(S): Racial differences exist for males undergoing fertility evaluation by a reproductive urologist. Better understanding of these differences in history in conjunction with societal and biologic factors can guide personalized care, as well as help to better understand and address disparities in access to fertility evaluation and treatment.

Treatment outcomes of laryngectomy compared to non-surgical management of T3 laryngeal carcinomas: a 10-year multicentre audit of 179 patients in the northeast of England.

OBJECTIVE: Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England. METHODS: The outcomes of T3 laryngeal carcinoma treatment at three centres (2007-2016) were retrospectively analysed using descriptive statistics and survival curves. RESULTS: Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy. CONCLUSION: Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.