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SARS-CoV-2 viral load | REGRESSION | Overall, at baseline mean (SD) and median (min–max) logBox plot presenting mean (cross within the box), median (horizontal line within the box), interquartile range, minimum and maximum logFigure LogMean logAvailable at The results of the random effects analysis showed that on a logRandom effects analysis of mean log* Significant at 5% (Linear regression analysis at each time point was used to determine if the mean logRegression analysis used to determine if Groups (1–3) differ in their mean log*Significant at 5% (The reference category is Group 4 (control) for each group comparison. | PMC10403620 |
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Discussion | infection, critically ill, illness, respiratory and cardiovascular disease | VIRUS, CRITICALLY ILL, DISEASE, INFECTION, OF DISEASE TRANSMISSION, CORONAVIRUS, ORAL INFECTION | This pilot study provided important information on the impact of three different mouthwashes containing 0.2% Chlorhexidine digluconate (CHX), 1.5% Hydroxide peroxide (HTo the best of authors’ knowledge this is the first clinical study to investigate the efficacy of different mouthwashes in reducing viral load in the saliva of COVID-19 patients with delta variant. Among the participants included in the present investigation, delta SARS-CoV-2 strain was the most prevalent whilst in other clinical studies the type of SARS-CoV-2 strain investigated was not disclosed. Previous studies have found that lower concentrations of CPC (10–40 μg/mL) presented anti-SARS-CoV-2 effects in many strains (Wuhan, Alpha, Beta, and Gamma). Meister et al.In the present study, SARS-CoV-2 viral load was assessed by RT-qPCR and was normalized to two reference genes; one external rat gene and another a human actin gene to consider extraction variation in human material. In previous studiesThe variability in the viral load, also observed in the control group of the present investigation, may be explained by naturally occurring changes in the shedding of viruses from other body niches like the nasopharynx. This information can be supported by the fact that persistent viral genetic material has been identified in upper respiratory samples weeks after the COVID-19 symptoms have disappeared. SARS-CoV-2 replicates abundantly in upper respiratory epithelia, where ACE2 is expressedDespite the mouthwashes used in the current study did not contain ethanol on their formulation, other commercially available mouthwashes can also be formulated with ethanol which could have contributed for reducing viral load. However, the majority of evidence available on the efficacy of mouthwashes in reducing viral load did not provide detailed information on the formulation of the mouth rinses investigated. In a study by Biber et al.SARS-CoV-2 viral RNA was detected in the saliva samples from 85% (45/53) of our patients diagnosed with COVID-19. On average, the mean time from the onset of symptoms to the study visit and saliva sample collection was around 8 days (ranging from 3 -18 days). The median incubation period from infection with SARS-CoV-2 to onset of symptoms is approximately 5 days with viral load reduction with recovery. Despite that, hospitalised individuals presenting with more severe illness are more likely to exhibit longer shedding of potentially infectious virus. Although the number of days from onset of symptom could have influenced the salivary viral load of the patients initially consented in this study, viral RNA was still detected in most of the saliva samples. Similarly, to the present investigation, previous studies were able to identify SARS-CoV-2 in 83.6–91.7% of the saliva samples obtained from COVID-19 positive patientsThe results from the present study should be considered in the context of some limitations. This study included critically ill hospitalized COVID-19 patients. Although participants were instructed and refrained from eating, drinking, or performing oral hygiene for at least 30 min prior each saliva sample collection, it was challenging to control and restrict the intake of drinks and food during the whole period of the study visit. In addition, most patients were on oxygen via nasal cannula which may have contributed to the reduction of the salivary flow. The authors also acknowledge that the inclusion of an additional group, who would rinse their mouth with saline or distilled water, would have allowed for a better understanding of the mechanical effect of rinsing on the outcomes. However, including the comparison of mouthwash use to not rinsing the mouth at all was deemed important to gather information on the saliva viral load specifically for those patients who did not perform any oral hygiene procedures. Furthermore, although in the present study patients taking antivirals or drugs that could have influenced salivary viral load were not excluded, the number of subjects taking medications were evenly distributed among groups and were unlikely to influence main results.Despite the current findings, the direct potential benefit of reducing SARS-CoV-2 load in the saliva of COVID-19 positive patient, in terms of disease transmission and patient wellbeing, is still unknown and needs to be further investigated. In future studies, the use of different or novel antimicrobial oral solutions could be established as a possible approach to either reduce transmission of coronavirus in the early stages of infection, especially among health professional (i.e., dentists, surgeons, and anaesthetists) or reduce viral load to potentially restrict virus transmission preventing future disease outbreaks. Additionally, it is not known if the reduction of salivary viral load could contribute to alleviate patients’ symptoms. Irrespective of its effect on SARS-CoV-2 salivary load, it is important to note the significance of maintaining good oral hygiene and care for patients diagnosed or suspected to have COVID-19 during and after infection resolves. Previous studies have demonstrated the importance of oral hygiene in overall health, particularly in hospitalized patients, and its association with various systemic conditions including respiratory and cardiovascular disease. Good oral hygiene practices, such as regular brushing, interdental cleaning, and mouthwash use, can contribute to maintain oral health and prevent oral infections, which can impact individuals overall well-being. | PMC10403620 |
Conclusion | DISEASE TRANSMISSION | Taking into consideration the findings and limitations of the present pilot study, it may be concluded that:The mouthwashes containing 0.2% CHX, 1.5% HThe marginally significant reduction in the average viral load observed in all study groups both at 2 and 3 h compared to baseline, may suggest a mechanical effect/action attributed to rinsing or spitting.Further, evidence from well-designed randomised clinical trials is required to fully understand the impact of oral hygiene and oral care products on viral load, disease transmission and patient wellbeing. | PMC10403620 |
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Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-39308-x. | PMC10403620 |
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Acknowledgements | RECRUITMENT | We acknowledge the contribution of all patients and study team members at each recruitment site. Most particularly, the research nurses Lisa Groarke and Bessie Cipriano. We also extend our thanks to the team members of the Centre for Oral Clinical Research (COCR) and Joint Research Management Office (JRMO) for Barts Health NHS Trust and Queen Mary University of London, who provided clinical and administrative support to the project. Haleon (prior GSKCH) is thanked for unconditional financial support and advice (Dr Stephen Mason and Dr Charlie Parkinson). | PMC10403620 |
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Author contributions | RECRUITMENT | N.D. was responsible for the concept of the study. J.P., N.G., M.T., and N.D. designed the trial and study protocol. J.P. was responsible for the site work including the recruitment, study visits and data collection. S.T. facilitated recruitment. S.T. and M.C.M. provided relevant medical advice and information. M.T. performed the viral load analysis. J.P., N.G., M.T., S.T., A.P., and N.D. contributed to the data interpretation. A.P. did the main statistical analysis. J.P., N.G., A.P., M.T., S.T., and N.D. prepared the manuscript. All authors reviewed and accepted the paper before submission. | PMC10403620 |
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Funding | GSK Consumer Healthcare (GSKCH) provided funding for this study as part of the | PMC10403620 |
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Data availability | The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. | PMC10403620 |
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Competing interests | N.D. had an advisory role at GlaxoSmithKline (GSK) and was awarded a GSK Consumer Healthcare (GSKCH) research grant, which provided funding for this study. ND has also lectured for Oral-B. S.T. is a GSK Global Health Consultant. J.P., N.G., A.P., M.T. and M.C.M. do not report any competing interest. | PMC10403620 |
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References | PMC10403620 |
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1. Introduction | non-communicable chronic diseases, Diabetes, T2DM, diabetes | DYSLIPIDEMIA, INSULIN RESISTANCE, DIABETES, TYPE 2 DIABETES, TYPE 2 DIABETES MELLITUS, DIABETES | These authors contributed equally to this work.(1) Background: We investigated the effects of a 12-week exercise intervention with or without vitamin D supplementation on insulin resistance and the plasma lipidome of participants with type 2 diabetes. We further explored whether the effects of the intervention on glycemic parameters could be associated with the baseline lipidome. (2) Methods: Sixty-one participants were randomly allocated to control (Con), exercise (EX), vitamin D (VD), and EX + VD groups. Multiple glycemic and anthropometric parameters were evaluated before and after intervention. The homeostasis model assessment of insulin resistance (HOMA-IR) was the primary outcome. The plasma lipidome was analyzed before, after, and at an additional 12-week follow-up. Machine learning was applied to establish prediction models for responsiveness of glycemic control. (3) Results: Our interventions failed to improve the HOMA-IR index while fasting glucose was reduced in the EX + VD group (change%, −11.9%; effect size, 0.65; Due to rapid social and economic development during the past three decades, China is facing a growing threat from non-communicable chronic diseases (NCDs), with diabetes considered to be one of the most common NCDs in China and several other countries [Endurance exercise has been recommended as an effective intervention for the prevention and treatment of type 2 diabetes mellitus (T2DM) by several associations, such as the American College of Sports Medicine and the American Diabetes Association. Moreover [Dyslipidemia is a well-known risk factor for T2DM, which is clinically characterized by abnormal regulation of total cholesterol and triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) [The primary aim of the present study was to investigate the effects of a 12-week endurance exercise training program with or without vitamin D supplementation on glycemic control (i.e., HOMA-IR and HbA1c), and its related plasma lipid species in participants with T2DM using lipidomics. We also assessed the post-intervention effects on lipids after an additional 12-week follow-up. In addition, our investigation was extended to investigate whether the basal plasma lipidome could predict the individual’s response to interventions in terms of glycemic control improvement. We hypothesized that exercise combined with vitamin D intervention would have synergistic effects on glycemic control and specific lipids, and the changes in lipids would be associated with glycemic improvement. Furthermore, basal specific lipids would have greater predictive potential for changes in glycemic control than traditional clinical indices. | PMC10346630 |
2. Methods | PMC10346630 |
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2.1. Study Design and Population | fracture, T2DM, hypoglycemic | ACUTE INFECTION, OSTEOPOROSIS, RENAL INSUFFICIENCY | The study was a randomized controlled trial with a 12-week intervention and additional 12-week follow-up period assessing the impact of vitamin D and exercise intervention on glycemic improvement in participants diagnosed with T2DM without insulin treatment in Xi’an, China (34° N latitude). Participants were excluded if they had (a) past insulin therapy or a plan to change hypoglycemic drugs during the trial; (b) ≥400 IU/day vitamin D supplementation for a month or regular exercise training; (c) acute infection; stress; heart, liver, and renal insufficiency; osteoporosis; or fracture; (d) a history of sunbathing at the beach, at a swimming pool, or anywhere else in the last six months; or (e) use of metal implants or other factors that could influence dual-energy X-ray absorptiometry (DXA) testing. Participants were randomly allocated into four groups using a computer-generated random number sequence: exercise + vitamin D group (EX + VD: Based on our previous study examining the association of vitamin D intervention with HOMA-IR [All of the procedures were reviewed and approved by the Ethics Committee of Xi’an Jiaotong University Health Science Center. The study was conducted in accordance with the Declaration of Helsinki and registered in the Chinese Clinical Trial System (No. ChiCTR1800015383). | PMC10346630 |
2.2. Intervention | PMC10346630 |
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2.2.1. Vitamin D Intervention | Participants in the EX + VD and VD groups took a daily vitamin D | PMC10346630 |
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2.2.2. Exercise Intervention | Participants in the EX and EX + VD groups participated in a supervised 1-h progressively increasing endurance cycling exercise at 65–80% of maximal heart rate (HRmax), 2 to 3 times/week, for 12 weeks at a gym. HRmax was predicted using the following formula: HRmax = (220 − age) [Flow diagram of participants ( | PMC10346630 |
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2.3. Data Collection | PMC10346630 |
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2.3.1. Anthropometric Measurements and Questionnaires | Body mass index (BMI) was calculated as body mass in kilograms divided by height in meters squared (kg/mPhysical activity information was obtained using the long form of the International Physical Activity Questionnaire (IPAQ), except for when participants were attending the exercise program. Metabolic equivalent task (MET) values in minutes/week were calculated [ | PMC10346630 |
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2.3.2. Glycemic Control Indicators | AutoSep, Venous fasting blood samples, high-density lipoprotein cholesterol | Venous fasting blood samples were collected at baseline (t1), 12 weeks (t2), and the 12-week follow-up (t3) after a 12-h overnight fast in Venoject-II AutoSep tubes with serum or NaF for plasma. Tubes with EDTA were used to determine blood glycosylated hemoglobin (HbA1c). Serum and plasma samples were transferred to separate tubes and frozen immediately at −80 °C. Fasting samples were used to measure the levels of plasma glucose, serum insulin, serum triglyceride, serum total cholesterol (TC), serum low-density lipoprotein cholesterol (LDL-C), serum high-density lipoprotein cholesterol (HDL-C), serum apolipoprotein (Apo)A-1, serum ApoB, and serum liver and renal function indicators (e.g., uric acid, creatinine, and γ-GT) by KingMed Diagnostics Inc. (Xi’an, China). At t1 and t2, a standard 75 g oral glucose tolerance test (OGTT) was also performed between 08:30 and 11:00, and plasma glucose and serum insulin levels were determined at 0, 30, 60, 90, and 120 min. Serum samples obtained at 6 and 12 weeks during the interventions were subjected to 25(OH)D analysis using electrochemiluminescence immunoassays (Roche Diagnostics GmbH, Mannheim, Germany). The intra- and inter-assay variation coefficients for 25(OH)D were 1.96% and 3.78%, respectively. The HOMA-IR index was the primary endpoint and calculated as follows: HOMA-IR = G | PMC10346630 |
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2.3.3. Plasma Lipidomic Profiling | COLD | Venous plasma samples collected at three time points (t1–t3) were used for lipidomics analysis using ultra-high-performance liquid chromatography–mass spectrometry (UPLC-MS/MS). The order of the plasma samples was randomized prior to extraction and instrumental analyses to minimize the influence of signal fluctuations. Pooled samples were used as quality controls throughout the analysis to verify the reproducibility. Details of instrumental analysis and data processing procedures including lipid extraction, peak detection, and lipid annotation are presented in In brief, 100 μL of plasma sample was properly mixed with 800 μL cold methyl tert-butyl ether and then mixed with 240 μL methanol. The mixture was vortexed for 30 s, sonicated at 4 °C for 20 min, and then centrifuged at 14,000× | PMC10346630 |
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2.4. Statistical Analysis | All statistical analyses were conducted using R 4.0.4 or SPSS 24.0. Descriptive statistics were calculated using mean ± standard deviation for continuous variables, Comprehensive changes in lipid profiles in response to different interventions were captured using the fuzzy c-means clustering algorithm (R package “Mfuzz”), followed by a paired Student’s test to assess differences between t1 and t2 in each treatment group. Data were auto-scaled prior to analysis. Specific attention was paid to lipids that were not altered in the Con group but showed pronounced changes between t1 and t2 in the VD, EX, or EX + VD groups (To identify lipids with similar physiological and molecular characteristics that were altered by EX, VD, or EX + VD intervention, a co-expression network of the plasma lipids was constructed using weighted gene correlation network analysis (R package “WGCNA”). A signed hybrid network and power of 8 were used for the scale-free topology criterion (model fitting index RPlasma lipids and/or measured clinical indices at baseline were subjected to a random forest algorithm incorporated into a repeated double cross-validation framework with unbiased variable selection (R package “MUVR”) to identify optimal panels of markers that could discriminate responders (i.e., participants who benefitted from the interventions and showed within-individual differences in glycemic control indicators before and after intervention) from non-responders (i.e., participants who underwent interventions but did not exhibit improved glycemic control indicators). Prediction accuracy was determined by misclassification rate % and area under the receiver operating characteristic curve (AROC, 95% CI). | PMC10346630 |
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3. Results | PMC10346630 |
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3.1. Baseline Characteristics of Participants | One participant in the VD group and another in the EX + VD group withdrew from the study due to personal reasons during the intervention. Additionally, 11 participants were lost to follow-up at t3. See more details in | PMC10346630 |
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3.2. Effects of Exercise and Vitamin D on Serum 25(OH)D Concentrations and Glycemic Control Indicators | Serum 25(OH)D concentrations were significantly increased in the EX + VD and VD groups, but they were not altered in the EX and Con groups (During the OGTT, compared with basal values, the levels of fasting glucose were relatively lower at five time points after EX + VD, VD, and EX interventions for 12 weeks. Opposite effects were seen for insulin concentrations. Such changes were not observed in the Con group ( | PMC10346630 |
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3.3. Effects of Exercise and Vitamin D on Plasma Lipidome | INSULIN RESISTANCE | A total of 1774 lipid features were identified and quantified, among which 1315 were annotated, including TGs (Among the lipid features, levels of 21 were increased by both VD and EX + VD interventions, while those of 7 were decreased (Mean ± standard deviation (SD) of blood parameters from baseline (0-week) for each group.Δ, change from the endpoint to baseline; EX + VD, exercise training and vitamin D supplementation group; VD, vitamin D supplementation group; EX, exercise training group; Con, control group; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; HbA1c, glycated hemoglobin; HOMA-IR, homeostasis model assessment of insulin resistance; AUC, area under the curve during oral glucose tolerance test. The increments in the AUC of glucose and insulin during the complete 120-min period of the OGTT were calculated using the trapezoid rule to assess glucose tolerance and insulin secretion. t1, time 1 (0-week); t2, time 2 (12-week). We further clustered those lipid features into co-expression modules to identify those with similar physiological and molecular characteristics, and 90 out of 105 lipids were successfully clustered into 2 modules (Most interestingly, we observed the regulatory effects of EX + VD intervention on certain plasma lipids, which could last until the 12-week follow-up ( | PMC10346630 |
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3.4. Individual Responses to Interventions Improving Glycemic Control and Baseline Prediction | T2DM | There was high inter-individual variability in multiple glycemic parameters in response to the interventions, which might have contributed to the lack of benefit of the VD and EX interventions and their combination on glycemic control, i.e., HOMA-IR in participants with T2DM (We conducted comprehensive machine learning analyses to identify baseline lipids that were associated with responsiveness and verified the model performance (Plasma lipidome responding to interventions at three sampling time points. (Alterations in plasma lipidome with interventions at three sampling time points. (Responders and non-responders to interventions and baseline prediction for HOMA-IR. ( | PMC10346630 |
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4. Discussion | T2DM | ADVERSE EVENTS, HYPERGLYCEMIA, DISEASE, DIABETIC COMPLICATIONS | In this randomized placebo-controlled trial, the overall beneficial effects of a 12-week endurance exercise training program with and without VD intervention on fasting glucose in participants with T2DM were observed, accompanied by notable alterations in the plasma lipidome. Although VD intervention failed to provide additional benefits to the HOMA-IR index and other glycemic indicators beyond EX intervention, we observed a regulatory effect of EX + VD intervention on the plasma lipidome and noted that such effects lasted until the 12-week follow-up. Some specific lipid changes were associated with changes in obesity-related traits. Importantly, we found high inter-individual variability in glycemic control indicators, i.e., HOMA-IR, HbA1c level, and glucose tolerance, as a result of our interventions, which to a great extent may explain the lack of synergistic improvement in glycemic control upon intervention. We thereafter identified several lipid species alone or in combination with clinical indices that largely improved the prediction of changes in glycemic control, with an AROC value over 0.9.Recently, a systematic review reported that combined exercise training (endurance and resistance exercises) was the most effective exercise intervention for cardiometabolic outcomes in participants with overweight and obesity [Hyperglycemia is a key risk factor for the development of diabetic complications [Recent advances in lipidomics have greatly expanded the associations between lipid species and metabolic pathways with disease onset and progression, such as T2DM [Moreover, maintaining appropriate levels of exercise as an effective strategy for keeping healthy can produce vast changes in multiple lipid species [Glycerophospholipids, in particular PCs and LPCs, play important roles in regulating glucose homeostasis and chronic inflammatory status [Apart from the observed effects of EX and VD interventions on glycemic control and the plasma lipidome, we found that the individual responsiveness of glycemic control indicator changes varied greatly among those undergoing interventions. For participants allocated in each intervention group, only about half were responders for HOMA-IR, HbA1c level, and glucose tolerance (i.e., participants who had lower glycemic indicators after intervention compared with baseline). These results corroborate and expand existing evidence that there are inter-individual differences in responses to diet or exercise treatments [Our findings explore the use of metabolomics in the fields of exercise metabolism and sports nutrition, promoting personalized exercise and/or nutrition strategies to maximize exercise performance and provide additional exercise-related health benefits, such as glycemic control. Additionally, no intervention-related adverse events were reported. These results indicated progressive and individual tailored programming may be effective in controlling body weight in participants with T2DM in a gym setting. Notably, although the frequency of attendance at exercise sessions did not differ between the EX and EX + VD groups, lower levels of adherence of some participants to the exercise program in the present study may have underestimated the effect of exercise on glycemic indicators, resulting in the inability to achieve significant results for blood indicators. Further comprehensive interventions targeting lifestyle, using novel approaches such as mHealth, are warranted to address this issues.Our study had several limitations. First, the study duration was relatively short, although it has been demonstrated that body fat and blood metabolic profile changes can be detected within 12 weeks [ | PMC10346630 |
5. Conclusions | T2DM | Although vitamin D supplementation failed to provide an additive effect beyond exercise on glucose homeostasis, we observed a regulatory effect of exercise combined with vitamin D intervention on the plasma lipidome. Such effects lasted until the 12-week follow-up in the EX + VD group, but this was not the case for the EX and VD groups. Moreover, the consideration of several lipid species at baseline could largely improve the prediction of changes in glycemic control rather than traditional clinical indices. Collectively, our data provide practical evidence that can be applied to exercise- and nutrient-specific conditioning programs for T2DM prevention and control. | PMC10346630 |
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Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC10346630 |
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Author Contributions | Research concept and design was created by X.S., L.S. and Y.W. Data screening and analysis were conducted by T.Y., Z.L. and S.Z. The manuscript was drafted and revised by X.S., L.S. and T.Y., and was critically revised by W.P., W.C., J.X. and Z.-B.C. Y.W. secured administration and financial support for the study. All authors have read and agreed to the published version of the manuscript. | PMC10346630 |
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Institutional Review Board Statement | All of the procedures were reviewed and approved by the Ethics Committee of Xi’an Jiaotong University Health Science Center. The study was conducted in accordance with the Declaration of Helsinki and registered in the Chinese Clinical Trial System (No. ChiCTR1800015383). | PMC10346630 |
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Informed Consent Statement | Not applicable. | PMC10346630 |
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Data Availability Statement | The data used in this study are not publicly available due to ethical reasons; the corresponding author can provide further information on these data upon reasonable request. | PMC10346630 |
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Conflicts of Interest | The authors declare that they have no competing interests. | PMC10346630 |
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References | PMC10346630 |
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Background | PJIs | Edited by: Marie Hallin, Université libre de Bruxelles, BelgiumReviewed by: Youliang Ren, University of Rochester Medical Center, United StatesChaitanya Tellapragada, Karolinska Institutet (KI), Sweden†These authors have contributed equally to this workMetagenomic next-generation sequencing (mNGS) is a culture-independent massively parallel DNA sequencing technology and it has been widely used for rapid etiological diagnosis with significantly high positivity rate. Currently, clinical studies on evaluating the influence of previous antimicrobial therapy on positivity rate of mNGS in PJIs are rarely reported. The present study aimed to investigate whether the positivity rate of mNGS is susceptible to previous antimicrobial therapy. | PMC10808557 |
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Methods | PJI | JOINT INFECTION | We performed a prospective trial among patients who undergone hip or knee surgery due to periprosthetic joint infection (PJI) to compare the positivity rate of culture and mNGS between cases with and without previous antimicrobial therapy, and the positivity rates between cases with different antimicrobial-free intervals were also analysed. | PMC10808557 |
Results | PJIs | Among 131 included PJIs, 91 (69.5%) had positive cultures and 115 (87.8%) had positive mNGS results. There was no significant difference in the positivity rate of deep-tissue culture and synovial fluid mNGS between cases with and without previous antimicrobial therapy. The positivity rate of synovial fluid culture was higher in cases with previous antimicrobial therapy. The positivity rates of mNGS in synovial fluid decreased as the antimicrobial-free interval ranged from 4 to 14 days to 0 to 3 days. | PMC10808557 |
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Conclusion | PJIs | mNGS is more advantageous than culture with a higher pathogen detection rate. However, our data suggested that antimicrobial agents may need to be discontinued more than 3 days before sampling to further increase the positivity rate of mNGS for PJIs. | PMC10808557 |
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Introduction | Periprosthetic joint infection, PJI, TJA | COMPLICATIONS | Periprosthetic joint infection (PJI) is one of the most serious complications following total joint arthroplasty (TJA) (Metagenomic next-generation sequencing (mNGS) is a culture-independent, massively parallel DNA sequencing technology that has been widely used for rapid aetiological diagnosis with significantly high positivity rates ( | PMC10808557 |
Materials and methods | PMC10808557 |
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Study population | infection, PJI, Musculoskeletal Infection | INFECTION | The present study was a prospective, single-centre clinical trial conducted in accordance with the World Medical Association Declaration of Helsinki and approved by the Ethics Committee of Honghui Hospital Affiliated to Xi’an Jiao Tong University. Written informed consent was obtained from all subjects. Patients with suspected knee or hip PJI who underwent surgery at our institution between January 2020 and December 2022 were included. Patients were diagnosed with PJI based on the diagnostic criteria of the Musculoskeletal Infection Society (MSIS) (Flowchart detailing the procedure of this study.Diagnostic data including serum C-reactive protein (CRP), serum erythrocyte sedimentation rate (ESR), synovial fluid white blood cell (WBC) count and polymorphonuclear neutrophil (PMN) percentage, and microbiological results were collected. Other data including patient age and sex, prosthesis site (hip or knee), type of infection (acute or chronic), and previous antimicrobial therapy including antimicrobial-free interval were collected. The positivity rate of culture and mNGS was compared between cases with and without previous antimicrobial therapy, and the positivity rate between cases with different antimicrobial-free intervals was also analysed. | PMC10808557 |
Sampling | STERILE | Synovial fluid and deep tissue were obtained at the time of surgery. Synovial fluid was collected in a sterile manner using an 18-gauge needle prior to arthrotomy, and samples were immediately divided into aerobic and anaerobic blood culture bottles (BACTEC 9240 system; BD Diagnostic Systems) for microbiology, a sterile container free of nucleases or other amplification inhibitors for mNGS, and an ethylenediaminetetraacetic acid (EDTA) vial for white blood cell count and differential. At least three different deep tissue samples were taken from periprosthetic tissue with the most obvious inflammatory changes and from medullary canals. Deep tissue samples were immediately divided into separate sterile vials for culture and histological analysis (more than 5 neutrophils per high-power field in 5 high-power fields observed was positive). All samples for microbiological testing were processed within 4 hours. All cases with at least 1 positive culture were considered positive. | PMC10808557 |
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Culture | ADVERSE EFFECT, POSITIVE | Deep tissue samples were homogenised and routine cultures, including aerobic and anaerobic bacterial cultures, fungal cultures and acid-fast bacilli cultures, were performed simultaneously. For synovial fluid culture, blood culture bottles were incubated on the BD-BACTEC-9240 instrument (BD Diagnostic Systems) for a total of 3 weeks if negative. Positive blood culture bottles were Gram stained and subcultured. Bacterial identification and drug susceptibility were performed using a Vitek II system (Biomerieux, USA). Quantitative culture methods were used from the samples and appropriate negative controls were established to avoid the adverse effect of contamination. | PMC10808557 |
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mNGS detection | The workflow for mNGS in synovial fluid included sample preparation, nucleic acid extraction, DNA library construction, metagenomic sequencing and bioinformatic analysis. Full details are available in | PMC10808557 |
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Data and statistical analysis | infection, PJI | CHRONIC INFECTIONS, INFECTION, POSITIVE | Patients with PJI were divided into acute and chronic infections according to the duration of infection, as described by To assess the concordance of microbiological results between positive culture and positive mNGS, categorisation was determined as follows: (i) complete concordance: identical organism detected, (ii) partial concordance: additional organism detected by culture or additional organism detected by mNGS, and (iii) discordance: different organism detected.Statistical analysis was performed using SPSS software (version 24, IBM Inc., Armonk, New York). Demographic data were described as mean and standard deviation (SD). Categorical variables were expressed as percentages. Student’s t-test was used to calculate differences between groups for continuous variables. Positive rates were calculated for microbiological and non-microbiological diagnostic tests. Chi-squared test or Fisher’s exact test was used to measure positivity rates between groups, as appropriate. McNemar’s test was used to compare mNGS and culture of samples within groups. The rank sum test was used to compare the number of mNGS pathogen sequencing reads between groups. Statistical significance was defined as p<0.05 (for two-tailed test). | PMC10808557 |
Results | PMC10808557 |
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General characteristics | aseptic failure, PJIs, PJI, Periprosthetic joint infection | Of the 167 screened cases with suspected hip or knee PJI, 36 cases were excluded due to aseptic failure (n=14), no culture or mNGS testing of synovial fluid (n=10), cement spacers in place at the time of sampling (n=6), unknown antimicrobial-free interval (n=5), and contamination in the operating room (n=1). The remaining 131 cases (84 knees and 47 hips) were included, including 76 cases with previous antimicrobial therapy (Patient demographic and baseline data of 131 PJIs.*The values indicate mean and standard deviation. #The values indicate the number of cases. †The values are the number of cases, with the percentage in parentheses. PJI, Periprosthetic joint infection; MSIS+, MSIS positive; MSIS-, MSIS negative; CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; WBC, White blood cell; PMN, Polymorphonuclear neutrophil. | PMC10808557 |
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Diagnostic performance of non- and microbiologic tests | PJIs | The positivity rates of all non-microbiological and microbiological diagnostic tests are shown in Positivity rates of non- and microbiologic tests.The results are shown as numbers of cases (percentages). CRP, C-reactive protein; ESR, Erythrocyte sedimentation rate; PMN, Polymorphonuclear neutrophil. SF, Synovial fluid; DT, Deep tissue. mNGS, Metagenomic next-generation sequencing.Of the 131 cases, 66 (50.4%) had positive synovial fluid cultures, 59 (45.0%) had two or more positive deep tissue cultures, 81 (61.8%) had one or more positive deep tissue cultures, and 22 (16.8%) had a single positive deep tissue culture. In addition, of the 22 cases with single positive deep tissue cultures, 17 (77.3%) were found to have identical pathogens in synovial fluid culture and/or mNGS testing. In the remaining 5 cases, the pathogen detected in the single positive tissue culture did not correlate with the pathogen detected in the synovial fluid cultures or mNGS tests, suggesting the possibility of contamination. When combining positive synovial fluid cultures and positive deep tissue cultures, the overall positivity rate was 69.5% (91 of 131 cases), which was a significantly lower percentage compared to the positivity rate of mNGS (115 of 131 cases [87.8%], p < 0.001). When compared with all cultures from all sources (deep tissue and synovial fluid), mNGS was able to identify identical pathogens in 90.1% (82/91) of culture-positive PJIs, with additional potential pathogens detected in 15.4% (14/91). Potential pathogens were detected in 70.0% (28/40) of culture-negative PJIs. | PMC10808557 |
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Influence of previous antimicrobial therapy on microbial results | acute infection, PJIs, chronic infection (N=75).In, infection | ACUTE INFECTIONS, INFECTION, CHRONIC INFECTIONS, ACUTE INFECTION | In the group with prior antimicrobial therapy, the positivity rate of mNGS was 88.2% (67 of 76), which was significantly higher than that of all cultures in all courses (synovial fluid and deep tissue) (58 of 76 [76.3%], p=0.004). In the group without prior antimicrobial therapy, the positivity rate of mNGS was 87.3% (48 of 55), which was significantly higher than that of all cultures in all courses (synovial fluid and deep tissue) (33 of 55 [60.0%], p= 0.013).Almost all non-microbiological and microbiological tests showed a higher positivity rate (with or without statistical difference) in the group with prior antimicrobial therapy compared to the group without prior antimicrobial therapy (Positivity rate of (non-) microbiologic tests according to prior antimicrobial therapy: with antibiotics (N=76) and without antibiotics (N=55).The rate of previous antimicrobial therapy was significantly higher in acute PJIs (39 of 56 cases [69.6%]) than in chronic PJIs (37 of 75 cases [49.3%], p=0.020). Comparison of positivity rate of microbiologic tests between acute infections and chronic infections in separate group with or without previous antimicrobial therapy are shown in Positivity rate of microbiologic tests according to classification of infection: acute infection (N=56) and chronic infection (N=75).In relation to the sequencing read counts which was regarded as a semi-quantitative indicator of the detected pathogens abundance, the average number of reads for the top known pathogen identified in cases with previous antimicrobial therapy and without previous antimicrobial therapy was comparable (453.4 ± 1407.3 vs 428.3 ± 660.2, p=0.079), as was that for acute PJIs in both groups (643.8 ± 1797.5 with previous antimicrobial therapy vs 685.1 ± 1015.1 without previous antimicrobial therapy, p=0.289). While, the average number of reads for the top known pathogen identified in chronic PJIs was significantly higher in cases without previous antimicrobial therapy than cases with previous antimicrobial therapy (311.5 ± 380.1 vs 226.1 ± 669.4, p=0.033). | PMC10808557 |
Influence of different antimicrobial-free intervals on microbial results | Comparison of the positivity rate of deep tissue culture (≥1 positive culture), synovial fluid culture and mNGS during different antimicrobial-free intervals is shown in Positivity rate of microbiologic tests according to no. of days before surgery when antimicrobial therapy was discontinued. SF, Synovial fluid; DT, Deep tissue. | PMC10808557 |
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Concordance of microbial results | PJIs, PJI | JOINT INFECTION | The pathogens based on their frequency of isolation by culture and detection by mNGS are shown in Correspondence between culture growth and the pathogen detected by mNGS.*The values are given as the detected frequency of a corresponding pathogen in all specimens. mNGS, Metagenomic next-generation sequencing.Including Including Including Including Including Including Including Including Including Pathogens from partial concordant, discordant and negative-culture PJIs in the subset of patients with previous antibiotics therapy.PJI, Periprosthetic joint infection; mNGS, Metagenomic next-generation sequencing.Similarly, in cases without prior antimicrobial therapy, 16 cases (29.1%) tested positive for mNGS but negative for culture, 1 case (1.8%) tested negative for mNGS but positive for culture, 6 cases (10.9%) showed identical negative results, and 32 cases (58.2%) showed both positive culture and mNGS results. Of the 32 double-positive cases, there was complete concordance between culture and mNGS results in 24 cases (75.0%). Eight cases showed partial concordance (5 of 32 [15.6%]) or discordance (3 of 32 [9.4%]) of the microbial findings (Pathogens from partial concordant, discordant and negative-culture PJIs in the subset of patients without previous antibiotics therapy.PJI, Periprosthetic joint infection; mNGS, Metagenomic next-generation sequencing.The complete concordance of positive mNGS and positive culture results was similar in both groups (44 of 55 [80.0%] with previous antimicrobial therapy vs. 24 of 32 [75.0%] without previous antimicrobial therapy, p=0.586). The overall concordance analysis of all cultures from all sources and mNGS results is shown in Distribution of mNGS and culture results in all cases (N=131) and concordance analysis between positive mNGS and positive culture cases (double positive, N=87). | PMC10808557 |
Comparison of the cost and turnaround time between culture and mNGS | ± | From sampling to reporting, the average days required for mNGS were 1.2 ± 0.4 and the average cost was 3234.6 ± 9.8 CNY. Meanwhile, the average turnaround time for culture results was 5.1 ± 2.6 days and the average cost was 696.8 ± 87.3 CNY. The turnaround time for obtaining the results of mNGS was significantly shorter than that of culture (t=9.688, p<0.001), and the cost of mNGS was significantly higher than that of culture (t=-241.3, p<0.001). | PMC10808557 |
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Discussion | PJIs, PJI, infections | INFECTIONS, COMPLICATION | PJI is a catastrophic complication following knee or hip arthroplasty, and microbial culture is considered the gold standard for pathogen identification and diagnosis. However, due to preoperative antimicrobial therapy, the presence of biofilms and fastidious bacteria, the positivity rate has been low (A total of 131 PJIs were included in this study. There were 115 patients with positive mNGS results and 91 patients with positive cultures. The positivity rate of mNGS in synovial fluid (87.8%) is significantly higher than in synovial fluid (50.4%) or deep tissue (61.8%) or the combination of two sources (69.5%). Compared with all cultures from all sources (synovial fluid and deep tissue), synovial fluid mNGS identified identical pathogens in 90.1% (82/91) of culture-positive PJIs, with additional potential pathogens detected in 15.4% (14/91). Meanwhile, new potential pathogens were detected in 70.0% (28/40) of culture-negative PJIs, demonstrating its usefulness in difficult-to-diagnose infections. In our institution, antibiotics were not commonly used in patients with suspected PJI prior to aetiological testing, and vancomycin was used empirically only when PJI was confirmed and the pathogen was unclear. However, 9/26 potential pathogens detected by mNGS in the 40 culture-negative PJIs were not covered by vancomycin. This may be one of the main reasons for the failure of anti-infective therapy. mNGS may have the potential to be a new powerful tool for the diagnosis of PJI. Thoendel et al. used metagenomic shotgun sequencing to detect a wide range of PJI pathogens from 408 cerebrospinal fluid samples and suggested that this method has the potential to improve or change the identification of many difficult-to-detect pathogens (It is well known that the detection of pathogens by culture may be impaired in PJIs previously treated with antibiotics (In this study, no significant differences were found in the positivity rates of deep tissue culture and synovial fluid mNGS between cases with and without prior antimicrobial therapy. However, the positivity rate of synovial fluid culture was higher in cases with previous antimicrobial therapy than in cases without antibiotics (57.9% vs 40.0%, p=0.043). It appears that the administration of antimicrobial therapy had no effect on the diagnostic microbial yield. These findings contrasted with those of previous studies confirming the influence of prior antimicrobial therapy on the detection rate (In this study, the average number of days required for culture was 5.1 days and 1.2 days for mNGS. Although the cost of mNGS was higher than that of culture, considering the higher positivity rate and earlier resolution capability, mNGS was more beneficial for early targeted antibiotic therapy for PJI. According to a study by Another interesting finding in this study was that the trends in culture and mNGS positivity rates with different antimicrobial-free intervals. The positivity rates of deep tissue culture and synovial fluid culture all decreased with shortening of the antimicrobial-free interval (>14 days, 4 to 14 days, 0 to 3 days) in patients receiving antimicrobial therapy prior to sampling. For synovial fluid mNGS, although the positivity rate did not show a consistent downward trend, it did decrease as the antimicrobial-free interval increased from 4 to 14 days to 0 to 3 days. This may mean that antimicrobials should be discontinued more than 3 days before sampling to further increase the positivity rate of mNGS for PJI.There are several limitations to the present study, including the fact that no gold standard has yet been established for the diagnosis of pathogens in PJI. Contaminants would then be a potential interference for mNGS and culture, which could influence the analysis. The low incidence of PJI limited the sample size, which may reduce the accuracy of some statistical results in this study. The high cost of mNGS limited the use of mNGS in deep tissue samples to fully evaluate the influence of prior antimicrobial therapy on the detection rate. The type and duration of previous antimicrobials were not further analysed. In addition, this was a single-centre study, which may be subject to some bias. A multicentre study with a larger sample size should be carried out next. | PMC10808557 |
Conclusion | PJI | In conclusion, mNGS had a significantly higher positivity rate than culture in detecting PJI, suggesting that mNGS may be a promising tool for rapid aetiological diagnosis of PJI, especially in PJI patients with a negative culture result or history of antibiotic administration. However, our data suggest that antimicrobials should be discontinued more than 3 days prior to sampling to further increase the positivity rate of mNGS for PJI. | PMC10808557 |
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Data availability statement | The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: | PMC10808557 |
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Ethics statement | The studies involving humans were approved by the Ethics Committee of Honghui Hospital Affiliated to Xi’an Jiao Tong University. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. | PMC10808557 |
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Author contributions | HL | LH: Data curation, Funding acquisition, Project administration, Writing – original draft, Writing – review & editing. WB: Writing – review & editing. ZQ: Writing – review & editing. TM: Writing – review & editing. PX: Project administration, Supervision, Writing – review & editing. HL: Project administration, Supervision, Writing – review & editing. PW: Funding acquisition, Writing – review & editing. | PMC10808557 |
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Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10808557 |
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Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10808557 |
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Supplementary material | The Supplementary Material for this article can be found online at: Click here for additional data file.Click here for additional data file.Click here for additional data file. | PMC10808557 |
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References | PMC10808557 |
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Background | Academic Editor: Adam Kern This study explored the efficacy of the “ | PMC10049845 |
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Methods and Results | Of 99 patients with true bifurcation lesions, 38 patients underwent the “ | PMC10049845 |
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Conclusions | The “ | PMC10049845 |
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1. Introduction | Coronary bifurcation lesions | Coronary bifurcation lesions account for about 15%–20% of total PCI [ | PMC10049845 |
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2. Methods | PMC10049845 |
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2.1. Study Population | This study complied with the Helsinki Declaration and was approved by the institutional ethics committee of Fuwai Central China Cardiovascular Hospital, Zhengzhou University (Zhengzhou, China). All participants in the study provided written informed consent. This trial has been registered on the ClinicalTrials website (This study was a single-center study where 107 patients were enrolled from Fuwai Central China Cardiovascular Hospital. Of these, 99 patients were randomized after screening for inclusion and exclusion criteria over the period from October 2021 to January 2022. Randomization was performed using a computer-generated list and SPSS software (IBM SPSS 25.0; SPSS Inc., Armonk, NY). Eighty-two patients underwent a 6-month angiographic followup ( | PMC10049845 |
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2.2. PCI Procedure | stenosis | STENOSIS | A radial artery approach was used in all patients. All stents were second-generationdrug-eluting stents and all the DCBs were SeQuent® Please (B. Braun, Melsungen, Germany). The size of semicompliant balloon, noncompliant (NC) balloon, cutting balloon, DCB, and stent was determined by the operator. The DCB was inflated within 120 s of entry into the body and inflated for 30–60 s. According to the current requirements, before DCB release, the following needs to be met: residual stenosis not greater than 30%, and no flow-limiting dissection (the processing strategy pattern diagram for different groups is shown in | PMC10049845 |
2.3. Technical Details | In group In group In group After percutaneous coronary intervention (PCI), all patients received dual antiplatelet therapy (DAPT) for at least 6 months. Secondary prevention medications were prescribed according to current guidelines and patient tolerance. | PMC10049845 |
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2.4. Followup | Clinical followup was performed by office visit or telephone at 30 days and every 3 months after discharge. Patients were advised to return for coronary angiography at 6 months ± 14 days. | PMC10049845 |
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2.5. Study Outcomes | acute gain, restenosis, MLD | ACUTE MYOCARDIAL INFARCTION, CARDIAC DEATH, SECONDARY, MLD, CARDIAC EVENTS, RESTENOSIS | The primary outcome was late lumen loss (LLL) of the MV and SB. The secondary outcomes were minimum lumen diameter (MLD) and acute gain and restenosis. In this study, we divided the SB into two parts for separate analysis. These parts were the “ostium,” which is about 3–5 mm from the beginning of the SB and the “shaft,” which is about 3–5 mm away from the ostium part. In terms of in-hospital and long-term clinical outcomes; we focused on major adverse cardiac events (MACEs: acute myocardial infarction, cardiac death, target vessel revascularization). | PMC10049845 |
2.6. Quantitative Coronary Analysis (QCA) | restenosis, stenosis | RESTENOSIS, STENOSIS | QCA was analyzed using Cardiovascular Angiographic Analysis System (CAAS) II software version 5.0 (Pie Medical Imaging, Maastricht, the Netherlands). Analysis was performed by two cardiologists separately. At followup, restenosis was defined as a QCA diameter stenosis ≥50%. The analysis was performed independently by two physicians blinded to the group, and the results were averaged. | PMC10049845 |
2.7. Statistical Analysis | Baseline characteristics are reported as counts and percentages or mean ± standard deviation (SD). The chi-square test was used to compare categorical variables. Comparison of means between multiple groups was performed using analysis of variance (one-way ANOVA) followed by Bonferroni's posthoc tests. All statistical analyses were performed using SPSS software v25.0 (IBM, Armonk, NY, USA). | PMC10049845 |
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3. Results | PMC10049845 |
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3.1. Baseline and Procedural Characteristics | A total of 99 patients were recruited and randomized, resulting in 33 in group Procedural characteristics are shown in | PMC10049845 |
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3.2. Clinical Outcomes | Two patients in group | PMC10049845 |
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3.3. Angiography Followup | Followup angiography after 6 months was performed in 82.83% (82/99) of patients ( | PMC10049845 |
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4. Discussion | stenosis | STENOSIS, PLAQUE | This study evaluated the clinical and angiographic outcomes of a new strategy we proposed to deal with the true coronary bifurcation lesions. The major findings were: (1) the “Mainstream strategies have their pros and cons. The two-stent strategy can solve the stenosis of the SB ostium caused by plaque shift and carina shift followed by MV stent implantation, and the immediate effect is better than the single-stent strategy [Herrador et al. [The “The “ | PMC10049845 |
4.1. Study Limitations | This study was a single-center study with a small sample size, which reduces the generalizability of the results. The next step is to perform a multi-center randomized controlled study to provide more evidence of the feasibility of this technique. Intracoronary imaging (intravascular ultrasound or optical coherence tomography) was not performed in most patients due to the high cost, and therefore, data related to the lumen area could not be obtained. However, the benefits of the “ | PMC10049845 |
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5. Conclusion | The “ | PMC10049845 |
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Acknowledgments | The authors thanked Editage for language correction support. This work was supported by the Natural Science Foundation of Henan Province (Grant no. 202300410465), 23456 Talent Project of Henan Provincial People's Hospital (Grant no. ZC23456132), and Henan Province Medical Science and Technology Research, Provincial and Ministerial Joint Construction of Major Projects (Grant no. SBGJ202101006). The funding source did not influence any part of the submitted work, including the study design, collection, analysis, and interpretation of data, in the article's writing, and the decision to submit for publication. | PMC10049845 |
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Data Availability | The data used to support the findings of this study are available from the corresponding author upon request. | PMC10049845 |
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Ethical Approval | This study was approved by the institutional ethics committee of Fuwai Central China Cardiovascular Hospital, Zhengzhou University (Zhengzhou, China) (No. 2021 [08]). | PMC10049845 |
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Conflicts of Interest | The authors declare that they have no conflicts of interest. | PMC10049845 |
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Supplementary Materials | SD | AMI, ACUTE MYOCARDIAL INFARCTION | Supplementary Figure 1: step-by-step diagram of the “Click here for additional data file.Research flow chart diagram.Panel (a) is a pattern diagram of a true bifurcation lesion, with measurement points marked. Panel (b) represents the “Statistically significant compared to the “Clinical baseline characteristics of groups.Values are mean ± SD or Lesion and procedural characteristics at pre- and post-PCI.
Clinical outcomes.TVR: target vessel revascularization; AMI: acute myocardial infarction.Angiography follow-up outcomes.
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Abstract | PMC9939163 |
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Background | esophageal cancer | ESOPHAGEAL CANCER, OESOPHAGEAL CANCER | The treatment of most esophageal cancer patients includes chemo(radio)therapy and extensive surgery, causing physical decline with loss of muscles. This trial aimed to test the hypothesis that a tailored home‐based physical activity (PA) intervention improves muscle strength and mass in patients having undergone curative treatment for esophageal cancer. | PMC9939163 |
Methods | esophageal cancer, muscle mass | OESOPHAGEAL CANCER | Patients operated for esophageal cancer 1 year earlier were included in a nationwide randomized controlled trial in Sweden in 2016–2020. The intervention group was randomized to a 12‐week home‐based exercise program, while the control group was encouraged to maintain routine daily PA. The primary outcomes were changes in maximal/average hand grip strength measured with hand grip dynamometer and lower extremity strength measured using 30‐second chair stand test and muscle mass measured using a portable bio‐impedance analysis monitor. Intention‐to‐treat analysis was used, and results were presented as mean differences (MDs) with 95% confidence intervals (CIs). | PMC9939163 |
Results | Among 161 randomized patients, 134 completed the study, 64 in the intervention group and 70 in the control group. Compared with the control group (MD 2.73; 95% CI 1.75–3.71), patients in the intervention group (MD 4.48; 95% CI 3.18–5.80) had statistically significantly ( | PMC9939163 |
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Conclusion | esophageal cancer, lower extremity muscle, lower extremity muscle strength | OESOPHAGEAL CANCER | A home‐based PA intervention 1 year after surgery for esophageal cancer improves lower extremity muscle strength.Patients operated for esophageal cancer 12 months earlier benefited from a home‐based physical activity exercise program. The 12‐week, home‐based exercise program with resistance training showed an improvement in lower extremity muscle strength. Home‐based physical activity in long‐term esophageal cancer survivors may improve rehabilitation.
| PMC9939163 |
INTRODUCTION | Esophageal cancer | ESOPHAGEAL CANCER, DISEASE | Esophageal cancer is a debilitating disease with poor overall survival. | PMC9939163 |
METHODS | PMC9939163 |
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Study design and participants | Cancer | CANCER | The Physical Activity (PA) study was a Swedish nationwide, two‐armed, multi‐centre randomized controlled trial (RCT) with 1:1 allocation during the study period 2016–2020. Ethical approval was obtained from the Regional Ethical Review Board in Stockholm, Sweden (Dnrs:2015/2142–32; 2016/1696–32/1; 2018/1447–32) and the study was registered with The study participants were recruited from within the framework of a nationwide and prospective data collection in Sweden, The Oesophageal Surgery in Cancer patients: Adaptation and Recovery study (OSCAR), presented in detailed elsewhere.Participant CONSORT flow diagram of the progress through the phases of the Physical Activity study trial for the intervention and control groups regarding the primary outcomes | PMC9939163 |
Randomization | All patients were provided oral and written information about the study at a visit by a research nurse and those who agreed to participate provided consent. The randomization procedure (block randomization) was conducted by an external organization outside the research group (Karolinska Trial Alliance, KTA) to avoid selection bias by anonymising the patient ID. Due to the nature of the intervention, it was not possible to conceal the participants' group allocation to neither patients nor researchers involved. However, the participants' allocation to intervention or control groups was masked in the dataset available for researchers during data analysis. Half of the eligible patients were randomized to intervention with home‐based exercise and half to standard care (control group). | PMC9939163 |
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Intervention versus standard care | esophageal cancer | OESOPHAGEAL CANCER | The intervention consisted of a 12‐week, home‐based exercise training based on previous data.Tailored home‐based strength training for long‐term survivors of esophageal cancer who underwent surgical resection
| PMC9939163 |
Compliance | The intervention group were followed up weekly by telephone by the research dietician/nurse to encourage adherence to the intervention. They were asked to report if during the past week they had performed the exercises as per the instructions received from the research nurse with the alternatives: (1) Yes, completely (2) Yes, but not all exercises (3) Yes, but only once (4) No, not at all. Compliance was assessed as “yes” (alternative 1 and 2) and as “no” (alternatives 3/4). | PMC9939163 |
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Measurements | muscle mass, hand dynamometer | SECONDARY | All measures of muscle strength and muscle mass were assessed objectively by the research dietician/nurse during the home visit both before randomization (baseline) and approximately 12 weeks after randomization.Muscle strength was assessed using two separate tests, one for hand grip strength and another for lower extremity strength. (1) Hand grip strength was measured using a hydraulic hand dynamometer (Model SH5001 JAMAR, SAEHAN Corporation, Changwon, S. Korea).Muscle mass was measured using a portable bio‐impedance analysis monitor (TANITA SC240MA), which measures body composition by placing the patient's feet on electrodes that measured resistance to an electrical signal (impedance). The technique is based on the principle that lean tissues have a high water and electrolyte content, and thus provides a good electrical pathway. The resistance measurement relates directly to the volume of the conductor, which is used to determine total body water, muscle mass (fat‐free mass) and fat mass.Changes in muscle strength were measured as the difference in absolute change in both maximal and average hand grip strength (dynamometer) and functional lower extremity strength (30‐second chair stand test) between baseline and shortly (within 2 weeks) after the 12‐week intervention period. Changes in muscle mass were assessed as the difference in absolute change in muscle mass (portable bio‐impedance analysis monitor) between baseline and shortly (within 2 weeks) after the 12‐week intervention period.The secondary outcomes, that is, patient reported outcomes, PA levels, and food intake were not included in the present article. | PMC9939163 |
Clinical data | tumor | TUMOR | For all included patients, copies of relevant medical records were retrieved from the hospitals, that is, predominantly from the seven university hospitals to provide additional clinical details about the tumor and treatment. These records were assessed according to a detailed predefined study protocol to ensure uniformity in the data collection. | PMC9939163 |
Sample size | muscle mass | The sample size was determined by the power calculations for the muscle strength and mass. Using one‐sided test and alpha at 0.05, sampling ratio 1, superiority margin of 0.001, to test the superiority of the intervention, 160 patients (80 patients per group after adjusting for 5% drop‐outs) were required for 80% power for detecting increase in muscle strength or muscle mass in at least 25% patients in the intervention group and ≤10% patients in the control group. An increase of 3% in muscle mass represented a minimum expected change. | PMC9939163 |
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