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PURPOSE: This article aims to analyze pediatric meningioma's imaging characteristics, especially those in unusual locations. METHODS: Pediatric patients with pathologically confirmed meningiomas at our hospital from January 2010 to January 2024 were enrolled. Meningiomas located in the cerebral convexity, parasagittal falcine region, anterior skull base, middle skull base, sphenoid ridge, cerebellopontine angle (CPA), olfactory groove, or juxtasella were considered in usual locations. Meningiomas found in other areas were considered in unusual locations. Clinical information, pathology results, and imaging features of pediatric meningiomas in usual and usual locations were analyzed and compared. RESULTS: A total of 18 patients (19 meningiomas) were enrolled, including 14 males and 4 females, with an average age of 14 years (ranging from 6 to 18 years). A total of 12 (63.2%) meningiomas were in the unusual location, including four (33.3%) were intraparenchymal, four (33.3%) were intraventricular, two (16.7%) were intraosseous, one (8.3%) case was in the paranasal sinus, and one (8.3%) was intraspinal. The meningiomas in unusual locations usually lacked the meningeal tail sign, and the misdiagnosis rate on preoperative imaging was significantly higher than that of meningiomas in usual locations. CONCLUSION: Pediatric meningiomas are prone to occur in unusual locations. When they occur in usual locations, they often lack typical radiographic features of meningiomas, leading to potential misdiagnosis before surgery. Recognition of the imaging characteristics of meningiomas in unusual locations in children may facilitate accurate preoperative imaging diagnosis.
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Hydrogen-tuned 185 nm vacuum ultraviolet (VUV/H2) photolysis is an emerging technology to destroy per- and polyfluoroalkyl substance (PFAS) in brine. This study discovered the promotive effects of two major brine anions, i.e., chloride and sulfate in VUV/H2 photolysis on the hydrated electron (eaq-) generation and perfluorocarboxylates (PFCAs) destruction and established a kinetics model to elucidate the promotive effects on the steady-state concentration of eaq- ([eaq-]ss). Results showed that VUV/H2 achieved near-complete defluorination of perfluorooctanoic acid (PFOA) in the presence of up to 1000 mM chloride or sulfate at pH 12. The defluorination rate constant (kdeF) of PFOA peaked with a chloride concentration at 100 mM and with a sulfate concentration at 500 mM. The promotive effects of chloride and sulfate were attributed to an enhanced generation of eaq- via their direct VUV photolysis and conversion of additionally generated hydroxyl radical to eaq- by H2, which was supported by a linear correlation between the predicted [eaq-]ss and experimentally observed kdeF. The kdeF value increased from pH 9 to 12, which was attributed to the speciation of the H·/eaq- pair. Furthermore, the VUV system achieved >95% defluorination and ≥99% parent compound degradation of a concentrated PFCAs mixture in a synthetic brine, without generating any toxic perchlorate or chlorate.
Subject(s)
Chlorides , Fluorocarbons , Hydrogen , Photolysis , Sulfates , Ultraviolet Rays , Kinetics , Fluorocarbons/chemistry , Sulfates/chemistry , Hydrogen/chemistry , Chlorides/chemistry , Salts/chemistry , Water Pollutants, Chemical/chemistry , CaprylatesABSTRACT
BACKGROUND: Data on the pathological responses and survival outcomes after neoadjuvant chemotherapy (NACT) in human epidermal growth factor receptor-2 (HER2)-low breast cancer (BC) are lacking. This study aims to investigate this topic in the real world. METHODS: Clinicopathological data from 819 HER2-negative BC patients who underwent NACT between 2010 and 2020 were retrospectively retrieved from the Shanghai Jiaotong University Breast Cancer Database. These patients were categorized into HER2-low and HER2-0 groups. Logistic analyses were conducted to identify predictors of complete pathological response (pCR) and breast pCR. Cox regression analyses were conducted to assess the factors associated with disease-free survival (DFS) and overall survival (OS). Kaplan-Meier (K-M) curves were generated to compare DFS and OS between HER2-low BC and HER2-0 BC. RESULTS: Of the 819 BC patients, 669 (81.7%) had HER2-low tumors, and 150 (18.3%) had HER2-0 tumors. HER2-low BC had a significantly higher ratio of ER ≥ 10%, PR ≥ 20%, and Ki67 ≥ 15% than HER2-0 BC. A significantly higher breast pCR rate was observed in HER2-low BC than in HER2-0 BC (13.6% and 7.3%, respectively, P = .036). Age, HER2 status (low or 0), Ki67, and surgery options were associated with breast pCR in HER2-negative BC. In HER2-low BC, the pCR rate of ER ≥ 10% BC was significantly lower than that of ER < 10% BC, but the DFS and OS of ER 10% BC were significantly higher. The K-M curve showed no significant differences in DFS or OS between HER2-low and HER2-0 BC. Cox regression revealed that ER expression and histological grade (III vs. Iâ¼II) were significantly associated with survival in HER2-low BC. CONCLUSIONS: In this real-world data (RWD) study, a significantly higher breast pCR rate was found in HER2-low BC than in HER2-0 BC, although there was no significant difference in survival. Moreover, ER expression had a significant prognostic impact on HER2-low BC.
Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Receptor, ErbB-2 , Humans , Female , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/mortality , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Neoadjuvant Therapy/methods , Middle Aged , Retrospective Studies , Adult , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/methods , Aged , Prognosis , Receptors, Estrogen/metabolism , China/epidemiologyABSTRACT
BACKGROUND: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs. METHODS: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678. FINDINGS: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29). INTERPRETATION: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective. FUNDING: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.
Subject(s)
Obesity , Overweight , Adult , Humans , Overweight/drug therapy , Network Meta-Analysis , Topiramate/therapeutic use , Obesity/drug therapy , Weight Loss , Phentermine/adverse effects , Randomized Controlled Trials as TopicABSTRACT
The use of treated wastewater (TWW) for agricultural irrigation is a critical measure in advancing sustainable water management and agricultural production. However, TWW irrigation in agriculture serves as a conduit to introduce many contaminants of emerging concern (CECs) into the soil-plant-food continuum, posing potential environmental and human health risks. Currently, there are few practical options to mitigate the potential risk while promoting the safe reuse of TWW. In this greenhouse study, the accumulation of 11 commonly occurring CECs was evaluated in three vegetables (radish, lettuce, and tomato) subjected to two different irrigation schemes: whole-season irrigation with CEC-spiked water (FULL), and half-season irrigation with CEC-spiked water, followed by irrigation with clean water for the remaining season (HALF). Significant decreases (57.0-99.8 %, p < 0.05) in the accumulation of meprobamate, carbamazepine, PFBS, PFBA, and PFHxA in edible tissues were found for the HALF treatment with the alternating irrigation scheme. The CEC accumulation reduction was attributed to reduced chemical input, soil degradation, plant metabolism, and plant growth dilution. The structural equation modeling showed that this mitigation strategy was particularly effective for CECs with a high bioaccumulation potential and short half-life in soil, while less effective for those that are more persistent. The study findings demonstrate the effectiveness of this simple and on-farm applicable management strategy that can be used to minimize the potential contamination of food crops from the use of TWW and other marginal water sources in agriculture, while promoting safe reuse and contributing to environmental sustainability.
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OBJECTIVE: To develop a novel Laryngopharyngeal Reflux Disease (LPRD) model in Bama pigs through endoscopic cricopharyngeal myotomy. METHODS: A total of eight 8-month-old Bama pigs were randomly assigned to either the control or surgery group. Prior to intervention, upper esophageal sphincter (UES) manometry and laryngopharyngeal Dx-pH monitoring were conducted to establish baseline physiological parameters for each pig. Subsequently, the surgery group underwent endoscopic cricopharyngeal myotomy, while the control group did not. Two weeks postintervention, these procedures were repeated to evaluate changes in UES contractility and the occurrence of reflux events. At week eight postsurgery, mucosal tissues from both groups were harvested for histological analysis. Hematoxylin and eosin (H&E) staining was used to assess inflammation, while transmission electron microscopy (TEM) examined alterations in intercellular spaces and desmosomes. RESULTS: The mean UES pressures in the control and surgery groups were 59 ± 9 mmHg and 68 ± 12 mmHg, respectively. In the surgery group, there was a significant decrease in UES pressure 2weeks after the operation compared to preoperative values (P = 0.005), whereas no significant change was observed in the control group (P = 0.488). Laryngopharyngeal reflux (LPR) was successfully induced in the surgery group as evidenced by reflux events with pH <5.0, which were not detected in the control group. HE staining revealed marked inflammatory cell infiltration and submucosal gland expansion in throat tissues of the surgery group Bama pigs. TEM further showed enlarged intercellular spaces and reduced desmosome numbers in the laryngopharyngeal epithelium compared to controls. CONCLUSION: Given analogous throat epithelial structures to humans, Bama pigs are an appropriate species for an LPRD animal model. Endoscopic cricopharyngeal myotomy effectively induces LPR and observable pathological changes in Bama pigs, providing a valuable platform for further research into LPRD pathophysiology.
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AIMS: To assess the time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drugs. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, and Cochrane Library up to 18 November 2021, for randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing all anti-diabetic drugs with standard treatment or with each other on fracture in adults with type 2 diabetes. The study performed a one-stage network meta-analysis using discrete-time hazard regression with reconstructed individual time-to-event data. RESULTS: This network meta-analysis involved seven RCTs (65,051 adults with type 2 diabetes) with a median follow-up of 36 months and three propensity-score-based NRSs (17,954 participants) with a median follow-up of 27.3 months. Among anti-diabetic drugs, thiazolidinediones increased the overall hazard of fracture by 42% (95% credible interval [CrI], 3%-97%) and almost tripled the risk after 4 years (hazard ratio [HR], 2.74; 95% CrI, 1.53-4.80). Credible subgroup analysis suggested that thiazolidinediones increased the hazard of fracture only in females (HR, 2.19; 95% CrI, 1.26-3.74) but not among males (HR, 0.81; 95% CrI, 0.45-1.40). Moderate certainty evidence established that thiazolidinediones increase 92 fractures in five years per 1000 female patients. We did not find the risk of fractures with other anti-diabetic drugs including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. CONCLUSIONS: Long-term use of thiazolidinediones elevates the risk of fracture among females with type 2 diabetes. There is no evidence eliciting fracture risk associated with other anti-diabetic drugs.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Fractures, Bone , Thiazolidinediones , Male , Adult , Female , Humans , Hypoglycemic Agents/adverse effects , Network Meta-Analysis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/chemically induced , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Fractures, Bone/prevention & control , Thiazolidinediones/adverse effectsABSTRACT
Many contaminants of emerging concern (CECs) have reactive functional groups and may readily undergo biotransformations, such as methylation and demethylation. These transformations have been reported to occur during human metabolism and wastewater treatment, leading to the propagation of CECs. When treated wastewater and biosolids are used in agriculture, CECs and their transformation products (TPs) are introduced into soil-plant systems. However, little is known about whether transformation cycles, such as methylation and demethylation, take place in higher plants and hence affect the fate of CECs in terrestrial ecosystems. In this study, we explored the interconversion between four common CECs (acetaminophen, diazepam, methylparaben, and naproxen) and their methylated or demethylated TPs in Arabidopsis thaliana cells and whole wheat seedlings. The methylation-demethylation cycle occurred in both plant models with demethylation generally taking place at a greater degree than methylation. The transformation rate of demethylation or methylation was dependent on the bond strength of R-CH3, with demethylation of methylparaben or methylation of acetaminophen being more pronounced. Although not explored in this study, these interconversions may exert influences on the behavior and biological activity of CECs, particularly in terrestrial ecosystems. The study findings demonstrated the prevalence of transformation cycles between CECs and their methylated or demethylated TPs in higher plants, contributing to a more complete understanding of risks of CECs in the human-wastewater-soil-plant continuum.
Subject(s)
Parabens , Wastewater , Water Pollutants, Chemical , Humans , Water Pollutants, Chemical/analysis , Acetaminophen , Ecosystem , Soil , Methylation , Demethylation , Environmental MonitoringABSTRACT
AIMS: To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. MATERIALS AND METHODS: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. RESULTS: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). CONCLUSIONS: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass.
Subject(s)
Diabetes Mellitus, Type 2 , Adult , Male , Humans , Female , Diabetes Mellitus, Type 2/epidemiology , Cohort Studies , Retrospective Studies , Muscle, Skeletal , China/epidemiology , Risk Factors , IncidenceABSTRACT
Surface water runoff can transport contaminants offsite to downstream aquatic ecosystems. The prevalence of impervious surfaces in urban areas enhances surface runoff and contributes to contamination of urban surface streams. Urban areas have complex drainage systems for the conveyance of drainage water, however, there is a dearth of information on the distribution of contaminants within storm drain system structures. Pyrethroid insecticides are among the most used insecticides in urban areas, and trace levels of pyrethroids are known to exert toxicity to aquatic invertebrates. To investigate pyrethroid occurrence and distribution throughout an urban drainage system, samples of water, sediment, algae, and biofilm were collected from catch basins, open channels, and outfalls in Los Angeles County, California, during the dry season. From 3 catch basins, 7 open channels, and 7 outfalls, a total of 28 water samples, 4 sediment samples, 8 algae samples, and 4 biofilm samples were collected and analyzed. Pyrethroid concentrations above the reporting limit were detected in 89% of water samples and all sediment, algae, and biofilm samples, with bifenthrin and cyfluthrin being the most frequently detected compounds. The median total pyrethroid concentrations in water, sediments, algae, and biofilms were 27 ng/L, 88 ng/g, 356 ng/g, and 3556 ng/g, respectively. Bifenthrin concentrations in catch basins were found to be significantly higher than those in open channels or outfalls. Significant correlations were found for various metrics, including between pyrethroid partitioning in water samples and total suspended solids. These findings highlight the role of underground catch basins as a sink as well as a secondary source for contaminants such as pyrethroid insecticides. Prevention of the input of these urban originated contaminants to catch basins is crucial for protecting the water quality of urban surface waters.
Subject(s)
Insecticides , Pyrethrins , Water Pollutants, Chemical , Animals , Insecticides/toxicity , Ecosystem , Water Pollutants, Chemical/analysis , Pyrethrins/toxicity , Geologic Sediments/chemistryABSTRACT
To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19.
Subject(s)
Antiviral Agents , COVID-19 Drug Treatment , COVID-19 , Ritonavir , Adult , Humans , Antiviral Agents/therapeutic use , Retrospective Studies , Ritonavir/therapeutic useABSTRACT
Immunotherapy is garnering increasing attention as a therapeutic strategy for breast cancer (BC); however, the application of precise immunotherapy in BC has not been fully studied. Further studies on BC immunotherapy have a growing demand for preclinical models that reliably recapitulate the composition and function of the tumor microenvironment (TME) of BC. However, the classic two-dimensional in vitro and animal in vivo models inadequately recapitulate the intricate TME of the original tumor. Organoid models which allow the regular culture of primitive human tumor tissue are increasingly reported that they can incorporate immune components. Therefore, organoid platforms can be used to replicate the BC-TME to achieve the immunotherapeutic reaction modeling and facilitate relevant preclinical trial. In this study, we have investigated different organoid culture methods for BC-TME modeling and their applications for precision immunotherapy in BC.
Subject(s)
Breast Neoplasms , Neoplasms , Animals , Humans , Female , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Neoplasms/pathology , Immunotherapy/methods , Organoids/pathology , Tumor MicroenvironmentABSTRACT
Contaminants of emerging concern (CECs) in the environment undergo various transformations, leading to the formation of transformation products (TPs) with a modified ecological risk potential. Although the environmental significance of TPs is increasingly recognized, there has been relatively little research to understand the influences of such transformations on subsequent ecotoxicological safety. In this study, we used four pairs of CECs and their methylated or demethylated derivatives as examples to characterize changes in bioaccumulation and acute toxicity in Daphnia magna, as a result of methylation or demethylation. The experimental results were further compared to quantitative structure-activity relationship (QSAR) predictions. The methylated counterpart in each pair generally showed greater acute toxicity in D. magna, which was attributed to their increased hydrophobicity. For example, the LC50 values of methylparaben (34.4 ± 4.3 mg L-1) and its demethylated product (225.6 ± 17.3 mg L-1) differed about eightfold in D. magna. The methylated derivative generally exhibited greater bioaccumulation than the demethylated counterpart. For instance, the bioaccumulation of methylated acetaminophen was about 33-fold greater than that of acetaminophen. In silico predictions via QSARs aligned well with the experimental results and suggested an increased persistence of the methylated forms. The study findings underline the consequences of simple changes in chemical structures induced by transformations such as methylation and demethylation and highlight the need to consider TPs to achieve a more holistic understanding of the environmental fate and risks of CECs.
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Mucocele is a benign, expansile, and oppressive lesion, more common in the frontal and ethmoid sinus and less in the maxillary sinus. Sinus mucocele mainly causes cheek swelling pain and nasal obstruction. In some cases, the paranasal mucocele grows large enough to compress periorbital structures and lead to impaired vision. Generally, mucocele is full of simple mucus, but pathogens can be found if co-infected, which means a poor prognosis. Functional endoscopic sinus surgery is an effective treatment for this disease. Here, the authors report a case that a mucocele occurred in the maxillary sinus, and a fungal ball was also found during the operation, which is a result of Paecilomyces farinosus co-infection.
Subject(s)
Mucocele , Paranasal Sinus Diseases , Humans , Mucocele/diagnostic imaging , Mucocele/surgery , Maxillary Sinus/diagnostic imaging , Maxillary Sinus/surgery , Maxillary Sinus/pathology , Treatment Outcome , Paranasal Sinus Diseases/diagnostic imaging , Paranasal Sinus Diseases/surgery , PainABSTRACT
OBJECTIVE: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. RESULTS: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). CONCLUSIONS: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022325948.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Kidney Failure, Chronic , Sodium-Glucose Transporter 2 Inhibitors , Adult , Humans , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Mineralocorticoid Receptor Antagonists/adverse effects , Network Meta-Analysis , Glucagon-Like Peptide-1 Receptor/therapeutic use , Quality of Life , Heart Failure/drug therapy , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia. METHODS: Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence. RESULTS: Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s). CONCLUSIONS: In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures.
Subject(s)
Sarcopenia , Female , Humans , Aged , Network Meta-Analysis , Sarcopenia/therapy , Exercise/physiology , Exercise Therapy , Muscle Strength/physiologyABSTRACT
BACKGROUND: A cyst with mural nodule(s) (CMN) is a rare imaging finding of cerebellar metastasis (CMET). It is a great challenge to differentiate it from cerebellar hemangioblastoma (CHB). In the present study, we explore the differences in the magnetic resonance imaging (MRI) characteristics of the 2 tumors. METHODS: Patients with pathologically confirmed CMET or CHB at our hospital from July 2009 to September 2021 were enrolled in the present study. All the patients underwent conventional head MRI (before and after contrast administration) before surgery and had ≥1 lesion in the cerebellum that presented as CMN on MRI. The clinical and MRI features were compared between the 2 groups. RESULTS: A total of 33 patients (10 with CMET and 23 with CHB) met the study criteria. The CMET patients were significantly older than were the CHB patients (median age, 59.5 years vs. 37 years; P = 0.002). Compared with the CHB group, the CMET group showed significantly higher occurrence rates of multiple mural nodules (72.7% vs. 8.7%), lack of vascular flow voids (100% vs. 65.2%), isointense or hypointense mural nodules on fluid-attenuated inversion recovery imaging (100.0% vs. 22.7%), restricted diffusion of mural nodules (22.2% vs. 0.0%), mildly enhanced mural nodules (90.9% vs. 4.3%), and a ring-enhanced pattern of the cyst wall (100% vs. 8.7%; P < 0.05 for all). CONCLUSIONS: When CMN is detected in the cerebellum on MRI, older age, multiple mural nodules, absence of vascular flow voids, isointense or hypointense mural nodule on fluid-attenuated inversion recovery sequence, restricted diffusion of the mural nodule, mildly enhanced mural nodules, and a ring-enhanced pattern of the cyst wall are the clinical and imaging features that strongly indicate the likelihood of metastasis, rather than CHB.