Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Pengambilan logam berat oleh pokok daun kari (Murraya koeniggi) dalam tanih ultrabes dari Felda Rokan Barat, Kuala Pilah, Negeri Sembilan, Malaysia

Kajian ini telah dijalankan di kawasan tanih ultrabes di Felda Rokan Barat, Kuala Pilah, Negeri Sembilan. Sebanyak lima belas sampel tumbuhan dan substratnya telah diambil dari kawasan kajian dengan kaedah berkelompok. Tujuan kajian ini adalah untuk menentukan kandungan logam berat Fe, Ni, Cr, Mn, Co, Zn, Cu, Cd dan Pb di dalam tanih dan bahagian akar, batang dan daun tumbuhan. Koefisien penyerapan biologi (BAC) ditentukan secara perkiraan. Kandungan logam berat di dalam tumbuhan diekstrak secara penghadaman basah manakala kandungan di dalam tanih diekstrak dengan kaedah pengekstrakan berjujukan. Kandungan logam berat di dalam larutan ekstrak tanih dan tumbuhan ditentukan menggunakan spektrofotometer penyerapan atom kaedah nyalaan (FAAS). Hasil kajian menunjukkan kepekatan logam berat paling tinggi dalam substrat pokok daun kari Murraya koenigi adalah Fe, diikuti oleh Mn, Cr, Co, Ni, Zn, Cu, Cd dan Pb dengan purata kepekatan masing-masing sebanyak 1699.64 mg/kg, 532.59 mg/kg, 212.43 mg/kg, 195.02 mg/kg, 174.97 mg/kg, 48.11 mg/kg, 43.86 mg/kg, 3.65 mg/kg dan 0.48 mg/kg. Kepekatan logam berat tersedia bagi Mn dan Pb adalah lebih tinggi berbanding logam berat tersedia yang lain berdasarkan peratus. Kandungan Fe dan Mn adalah tinggi di dalam semua bahagian tumbuhan. Walau bagaimanapun, berdasarkan nilai purata kumulatif BAC, hanya logam Pb menunjukkan nilai penimbunan yang agak tinggi dalam tumbuhan. Kajian ini menunjukkan pokok daun kari (Murraya koenigi) bukan tumbuhan penumpuk logam berat berdasarkan kepada nilai BACnya yang rendah

Evaluation of antioxidant, antibacterial and anticancer activities of ganoderma lucidum extracts

G. lucidum is an oriental fungus loaded with antioxidant, antimicrobial and anticancer properties. G. lucidum extracts obtained by using soxhlet and Ultrasonic-Assisted Extraction (UAE). The antioxidant activity determined by DPPH assay resulting in IC50 value of extract for soxhlet water 372.21μg/mL followed by soxhlet ethanol 431.00μg/mL, UAE ethanol 541μg/mL and UAE water 560.90μg/mL shown weak antioxidant properties. Well plate diffusion used for antimicrobial activity test against E. coli and S. aureus. The UAE water extract shown highest antibacterial activity against S. aureus (20-23) mm followed by soxhlet water extract (6-13) mm. The ethanol extract for both soxhlet and UAE are (5-13) mm and (4-14) mm respectively. G. lucidum extract exhibited zero inhibition zone against E. coli due to presence of barrier membrane. CCK-8 used to test anticancer activity against MCF-7 cells. The IC50 values of soxhlet ethanolic extract is 4.797 μg/mL followed by UAE ethanolic extract 5.291 μg/mL, soxhlet water extract 7.196 μg/mL and UAE water extracts 9.455 μg/mL. The lower IC50 value indicated that the extracts inhibited cell viability of MCF-7

Influence of amang (Tin Tailing) on geotechnical properties of clay soil (Pengaruh amang timah terhadap sifat geoteknik tanih lempung)

Amang or tin tailing is commonly found in the vicinity of disused mining area and responsible in downgrading the water quality, landscape and mechanical behaviour of soils. It was generated from extraction process of separating valuable metal from particular ore. This paper presents the geotechnical characteristics of amang-contaminated clay soil. The geotechnical properties of uncontaminated soils were studied in order to compare to that of amangcontaminated soils. The base soil used in this study represents completely weathered horizon of metasedimentary rock. Meanwhile, tin tailing sample was taken from the disused mine at Sungai Lembing, Pahang. The geotechnical characterisations of base soil and contaminated soils were determined based on consistency index, compaction behaviour, hydraulic conductivity and undrained shear strength (UU tests). Contaminated soil samples were prepared by adding 5, 10 and 20% of tailing, based on dry weigh of the studied base soil. The results from the particle size distribution analysis showed that residual soil from metasedimentary rock comprised 42.6% clay, 32.2% silt and 25.2% sand whilst tailing was dominated by 98% of sand fraction. XRD analysis indicated the presence of quartz, kaolinite and muscovite minerals in the studied soil. The specific gravity of soil used is 2.67 and the pH is 3.88. Tailing found to have higher specific gravity of 3.37. The consistency index of contaminated soils showed that liquid limit, wL and plastic limit, wP decreased with the increase in the percentage of tailing added to the soil samples. The value of maximum dry density, ρ dry max increased while optimum moisture content decreased due to the increase in tailing content in soil sample. The permeability of contaminated soil also increased with the increase in tailing contents ranged from 19.8 cm/hr to 23.8 cm/hr. The undrained shear strength, Cu, of contaminated soil decreased from 646 kPa (5% of tailing) to 312 kPa (20% of tailing) suggesting that the presence of tailing has influenced the geotechnical properties on the studied soil

Impact of Mg rich synthetic gypsum application on the environment and palm oil quality

A study was conducted in an oil palm plantation in Peninsular Malaysia to elucidate the effects of applying Magnesium Rich Synthetic Gypsum (MRSG), a by-product of chemical plant, on the chemical properties of soil, the uptake of heavy metals by the palm trees, the oil quality and its impact on the surrounding environment. The results showed that MRSG application onto soil cropped to oil palm could bring positive impact in terms of soil chemical properties and oil palm production. The quality of the oil was not significantly affected by the continuous MRSG application as shown by the low heavy metals and trace elements of concern content (Cu: 0.062 mg/kg; Fe: 2.10 mg/kg; Mn: 1.93 mg/kg; Pb: 0.006 mg/kg; Zn: 0.103 mg/kg; Cr: 0.354 mg/kg; Ni: 0.037 mg/kg). From the I-geochem index, the soil was found to have values ranging from -3.81 to -1.03 which is considered as uncontaminated. Further, its application did not result in negative impact on the surrounding environment; hence, the quality of the soil and surface water in the plantation and/or the surrounding area remained intact. Phytotoxic elements in the oil palm tissue (As: 0.12 mg/kg; Se: 0.05 mg/kg; Zn: 1.48 mg/kg; Ce: 0.47 mg/kg; La: 0.26 mg/kg; Sr: 3.03 mg/kg) and cytotoxic elements in the oil were below the acceptable limit. Based on the results of the Environmental Monitoring out during the period of the study, it was concluded that application of the by-product of the chemical plant as a source of Mg to enhance soil fertility in the oil palm plantation was considered safe and sustainable. The effects of applying MRSG and Chinese kieserite was almost similar. So, MRSG can be used as a possible source of Mg to replace Chinese kieserite for oil palm production on the Ultisols in Peninsular Malaysia

Rivaroxaban with or without aspirin in stable cardiovascular disease

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58\ub75%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31\ub72%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10\ub72%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12\ub73%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9\ub74%] of 7339 patients), middle (549 [14\ub70%] of 3918 patients), and low (298 [23\ub72%] of 1282) HDI (p&lt;0\ub7001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17\ub78%] of 574 patients in high-HDI countries; 74 [31\ub74%] of 236 patients in middle-HDI countries; 72 [39\ub78%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1\ub760, 95% credible interval 1\ub705\u20132\ub737; p=0\ub7030). 132 (21\ub76%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16\ub76%) of 295 patients in high-HDI countries, in 37 (19\ub78%) of 187 patients in middle-HDI countries, and in 46 (35\ub79%) of 128 patients in low-HDI countries (p&lt;0\ub7001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication. Funding: DFID-MRC-Wellcome Trust Joint Global Health Trial Development Grant, National Institute of Health Research Global Health Research Unit Grant