Coal mining results in reduced soil quality and makes environments less stable. Soil fungi are suitable indicators of soil quality for monitoring purposes. Here, the objective was therefore to investigate the effects of grazing and mining on the composition of the soil fungal community at the periphery of an opencast coal-mine dump in the Shengli mining area, Xilingol League, Inner Mongolia. A total of 2,110 fungal operational taxonomic units were identified and subdivided into 81 orders and nine categories, based on trophic modes. The sensitive factor to mining was soil pH, and that to grazing were soil nitrate-nitrogen and alkaline phosphatase activity. According to the Pearson correlation and Mantel test, we propose interactions between grazing and coal-mining exist a co-effect and could regulate edaphic variables to alter the behavior of soil fungal community. Moreover, compared with coal-mining, grazing has a greater impact on it. The results provide a basis to further clarify soil fungal ecological functions, and may also contribute to the practice of soil remediation and environmental management in coal-mining areas. Opencast coal mining still has an important role in both energy production and environmental pollution , causingSoil fungi are a key component of below-ground biological communities and play an important role in decomposition and nutrient recycling through a number of microbiological and ecological processes . Soil fuin situ reclamation of coal mining areas. However, there is a lack of such studies in other types of ecosystems such as grasslands.Previous studies on the effects of coal mining on soil ecosystems have mostly considered soil microorganisms , enzyme The grassland environment around a mining area is also affected by anthropogenic interference such as livestock grazing. Grazing affects plant performance directly through the consumption of the above-ground parts of plants, and indirectly via effects on soil microbial community composition, by altering soil properties . BardgetStipa krylovii is a perennial bunchgrass and is representative of typical zonal habitats. S. krylovii is native to the Inner Mongolian steppe and is considered to be a constructive species for the ecological restoration of typical degraded grassland. The presence of soil fungi in the microbial community of the steppe soil means that S. krylovii plays a key role in sustaining the stability of the grassland ecosystem and its productivity  to analyze how coal mining and grazing exert their effects and to what extent.Here, we tested the hypothesis that soil fungal community composition and function change within a periphery of the opencast coal-mine dump and grazing. In addition, we investigated interactions between edaphic properties and soil fungal community changes. The objectives of this study were: (1) to investigate the diversity and distribution of soil fungal communities in the rhizosphere of S. krylovii, Aneurolepidium chinense, and Achnatherum splendens.The soil studied in the present investigation was located at the periphery of the opencast coal-mine dump in the Shengli mining area, Xilingol League, Inner Mongolia . This area is typical semi-arid grassland an average annual temperature of 0–3°C and average annual precipitation of 294.9 mm, with considerable seasonal and diurnal temperature variation. The soil is a meadow chestnut soil : routes A (AR) and B (BR) are grazing areas (main herbivores are sheep and horses), whereas route E (ER) is a restricted grazing area. The distances between the dump and the three sample plots on each route were 100, 900, and 1,900 m  were collected from the study area. Fresh sub-samples (10 g) of each were transferred from the field to the laboratory on ice and then stored at −80°C prior to DNA extraction and high-throughput sequencing. The remaining portion of each sample was sieved (<2 mm), air-dried and stored at 4°C prior to analysis of soil physicochemical properties.We sampled four replicates areas  in each of the sample plots with similar slopes, gradients, and altitudes . After r2SO4 (4+–N) and nitrate nitrogen (NO3––N) were extracted from fresh samples with 1 mol L–1 KCl and determined using an auto analyzer  were determined using a glass electrode in a soil: water suspension [1:2.5 (w/w)] with a pH meter  and in a [1:5 (w/w)] suspension with a conductivity meter , respectively. Soil organic matter (SOM) content was obtained from the percentage organic carbon determined by the dichromate oxidation method in the presence of H2SO4 . AmmoniuPRJNA682369).Soil microbial DNA was extracted from 0.1 g of homogenized soil from each fresh sub-sample using a MoBio PowerSoil DNA Isolation Kit  according to manufacturer’s instructions. PCR amplification was conducted using the internal transcribed spacer (ITS) between the large and small subunit rDNA genes, and specific primers ITS1F (5′-CTTGGTCATTTAGAGGAAGTAA-3′) with barcode and ITS2R . The representative sequence for each OTU was screened for further annotation to obtain taxonomic information using Unite Database.3 The detailed analysis processes for bioinformatics were shown by The raw sequences were calculated by QIIME (v.1.7.04) via the “phyloseq” package (Number of observed species (Sobs), abundance-based coverage estimate (ACE), Shannon–Wiener index and phylogenetic diversity (PD) were calculated and displayed using R software  and non-metric multidimensional scaling (NMDS) were carried out using R software (v.3.5.2) via the “vegan” package , using tP < 0.05) using SPSS . Kaleida Graph 4.05 was used for graphical plotting and presentation.Edaphic variables and fungal diversity indices were assessed by two-way analysis of variance (ANOVA). Comparisons between pairs of means were made using the Tukey’s honestly significant difference tests , Hypocreales (16.15%), unclassified_p__Ascomycota (12.56%), Sordariales (10.78%), Agaricales (10.84%), unclassified_k__Fungi (6.59%), and Eurotiales (3.55%). With reference to the FUNGuild database, OTUs were classified into nine categories, according to trophic modes, with the predominant modes being Saprotroph (28.55%), Pathotroph-Saprotroph-Symbiotroph (21.31%), Pathotroph (9.02%), Pathotroph-Saprotroph (5.93%), Saprotroph-Symbiotroph (1.97%), Symbiotroph (1.47%), Pathotroph-Symbiotroph (0.34%), and Pathogen-Saprotroph-Symbiotroph (0.13%), in addition to Unassigned 31.30%; . The relBased on the Venn diagram, the common and unique OTU numbers in multiple samples were calculated , with thP < 0.05, –1 at 1,900 m of routes E (ER) and with a minimum of 23.2 mg g–1 at 100 m of routes A (AR). Soil NH4+–N concentrations at 900 and 1,900 m of AR were significantly higher than concentrations at other sampling sites, while the lowest concentration was recorded at 1,900 m of routes B . Soil NO3––N concentration at 900 m of AR was also significantly higher than at other sampling sites (P < 0.05). AP concentrations at 900 and 1,900 m of ER were significantly higher than those at the other sites, and the minimum concentration was 7.17 mg kg–1 at 100 m of BR and the maximum reached 10.4 mg kg–1 at 1,900 m of ER. Soil available potassium (AK) concentrations ranged from 219 to 292 mg kg–1 at different sampling sites, with values at 1,900 m of AR and 1,900 m of ER being significantly higher than those at other sampling sites (P < 0.05).Soil organic matter also differed significantly, depending on the sampling sites (–1 h–1 (P < 0.05). ALP activity ranged from 238 to 310 μg g–1 h–1, the maximum value being recorded at 100 m of ER which was significantly higher than that at other sampling sites (P < 0.05). U activity at 1,900 m of ER was significantly higher than at other sampling sites (P < 0.05), with the lowest value occurring at 900 m of BR.The ACP activities at 900 m of ER, and at 900 and 1,900 m of AR were significantly lower than at other sampling sites, while the greatest activity was recorded at 100 m of BR, with a maximum value of 306 μg gF = 4.455, P = 0.001) and distances . NMDS shows that the fungal community composition was significantly affected by different routes and distances (3––N concentration (P < 0.001), ALP activity , ACP activity , EC (P = 0.034) and pH (P = 0.012).The range of Sobs of BR, from 622 to 785, was higher than those of AR (580–683) and ER 455–609; . In the istances . Fungal P < 0.05). Route had significant effects on edaphic variables, ACE, and PD (P < 0.05), whereas edaphic variables had close relationships with the diversity and composition of fungal communities. Soil EC, NH4+–N, and NO3––N concentration and ACP and ALP significantly influenced fungal community composition (P < 0.05). Soil pH and ALP were significantly and negatively correlated with Sobs, ACE, and PD. Soil NO3––N was significantly and negatively correlated with ACE (P < 0.05).The Pearson correlation and Mantel test showed significant relationships among route, distance, diversity and composition of fungal communities, and edaphic variables . DistancP < 0.05). LDA scores of groups were confirmed by LEfSe (Crinipellis), Atheliales (from order to genus), Talaromyces and Knufia. At 900 m, three groups were significantly predominated (Marasmiellus), Montagnulaceae (from family to genus) and Aspergillus. At 1,900 m, five groups were significantly predominated . In AR, 11 groups were significantly predominated , Agaricales , Capnodiales (order). In ER, four groups were significantly predominated , correlated with the establishment of partner species in the stages. Symbiotic fungi affect ecosystem functions by influencing plant community assembly and increasing plant productivity , 2012. AThe fungal community composition and edaphic variables were significantly affected by the distance from the dump, whereas edaphic variables significantly influenced fungal diversity indices by correlation analysis. The effect of distance from the site of coal mining activity on fungal diversity may have occurred through changes in edaphic variables. This finding is similar to the observations of Soil pH was an important variable controlling fungal community structure . The avaGrazing was previously found to reduce soil microbial respiration and activity, an observation which was suggested to result in decreased decomposition rate . Here, tIn respect of NMDS, the composition of the fungal community was significantly affected by grazing. Grazing likely modulates the soil fungal community by altering the competitive interactions between dominant fungi and releasing/suppressing subordinate fungi , or by d3––N under different grazing regimes in soil of the Loess Plateau and to be correlated with soil pH in grazed grassland on the Tibetan Plateau  and ALP activity. Interactions between grazing and coal mining show a coupling effect in the behavior of soil fungal communities. Future studies investigating the ecological functions of soil fungi would increase our understanding of the role of soil fungal communities in grassland coal-mining areas.Here, we demonstrate the detailed soil fungal community and soil nutrients at the periphery of an opencast coal-mine area. The diversity of the fungal community had its maximum values at the sampling plots farthest from the coal mining dump, but without linear relationship between diversity and distance. The sensitive factor to mining was soil pH. The sensitive factors to grazing were soil nitrate-nitrogen (NOhttps://www.ncbi.nlm.nih.gov/bioproject/ (accession number PRJNA682369).The original contributions presented in the study are publicly available. This data can be found here: YB and LX conceived and designed the experiments. LX and XL performed the experiments. LX and KW analyzed the data and language editing with the help of PC. All authors contributed to the article and approved the submitted version.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.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.


Background: Although clinical studies have shown an increased prevalence of primary open-angle glaucoma (POAG) in patients with Alzheimer’s disease (AD), a population-based epidemiologic study from Denmark found no increased risk of Alzheimer’s disease in patients with glaucoma, and other studies have failed to demonstrate a link. However, a possible relationship between POAG and AD might manifest in their association with oral pathology. Dental caries, periodontal disease, stomatitis, and the related inflammatory burden increase AD risk, while oral pathology and the oral microbiome correlate with POAG vulnerability. To further examine the relationship, we analyzed POAG, AD, and oral disease in the UK Biobank (UKBB) cohort.Methods: Our analysis included all subjects with POAG and AD. POAG diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD-10), H40.11. AD diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD-10), G30. Oral cavity, ulceration, stomatitis, periodontitis, teeth, and dental problems were in UKBB data field 6149.Results: A “yes” answer to a question about bleeding gums is associated with a greater proportional POAG reduction (24.2%) than a “yes” answer to having none of the six listed problems (6.3%). Similarly, bleeding gums were associated with a greater proportional AD reduction (46.2% versus 16.9%). Logistic regression controlling for age and sex showed that bleeding gums (no/yes) were negatively associated with AD (odds ratio (OR) = 0.713, 95% confidence interval (CI) = 0.521-0.976, p = 0.035). Age-weighted least-squares linear regression showed that the lower corneal-compensated intraocular pressure (IOP) in the left eye was associated with bleeding gums , controlling for type 2 diabetes and past smoking.Conclusion: It is difficult to predict what component or components of periodontal inflammation might be ameliorating POAG and AD. Prostaglandin is a possibility. Identification of the component or components could lead to new treatments for POAG and AD. Further studies are warranted. Glaucoma is a collection of ocular neuropathies marked by the degeneration of retinal ganglion cells (RGCs) and their axons, which results in a distinctive optic nerve appearance and visual field abnormalities. The most prevalent type of glaucoma is primary open-angle glaucoma (POAG). Glaucoma can lead to vision impairment and eventually blindness if not treated. Currently, intraocular pressure (IOP) is the sole known therapeutic component.The most prevalent cause of dementia in the elderly is Alzheimer’s disease (AD), a neurodegenerative condition that develops over time and is defined clinically as growing cognitive and behavioral impairment. β-Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer’s disease. The epsilon 4 allele of apolipoprotein E (APOE), which has been linked to POAG , is a suStructural examinations of optic nerves from patients with AD have revealed degeneration and loss of retinal ganglion cells, such as POAG. Caspase activation and the aberrant processing of amyloid precursor protein (APP), both essential processes in Alzheimer’s disease, have been demonstrated in a rat model of chronic ocular hypertension. In the same type of experimental glaucoma, β-amyloid has been linked to retinal ganglion cell (RGC) apoptosis. Therefore, POAG and AD may be part of the same age-related neurodegenerative process .Although clinical studies have shown an increased prevalence of POAG in patients with Alzheimer’s disease , a populA possible relationship between POAG and AD might manifest in their association with oral pathology. Dental caries, periodontal disease, stomatitis, and the related inflammatory burden increase AD risk ,9, whileTo further examine the relationship, we analyzed POAG, AD, and oral disease in the UK Biobank (UKBB) cohort.The UK Biobank is a major men’s and women’s prospective observational study. Between 2006 and 2010, participants were recruited from 22 different centers across England, Wales, and Scotland, and they are still being followed for future health events . The UKBOur UK Biobank application was approved as UKB project 57245 (SL and PHR). Our analysis included all subjects with POAG and AD, including concomitant. POAG diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD-10), H40.11. AD diagnosis was ascertained using the 10th Revision of the International Classification of Diseases (ICD-10), G30. Oral and dental problems were in UKBB data field 6149. A touchscreen question was presented to all subjects: “Do you have any of the following? (You can select more than one answer).” The choices were mouth ulcers, painful gums, bleeding gums, loose teeth, toothache, dentures, or none of the above. A subject could enter up to six responses. Data were collected during a single session, and no follow-up or longitudinal data were collected.Data processing was performed on Minerva, a Linux mainframe with Centos 7.6, at the Icahn School of Medicine at Mount Sinai. We used the UK Biobank Data Parser (ukbb parser), a python-based package that allows easy interfacing with the large UK Biobank dataset . StatistThe mean age of 349,549 subjects was 56 ± 8 (mean ± SD), 54% were female and 46% were male, and 95% were White British. Additional demographics are in the following tables.Oral cavity problems in subjects versus POAG (no/yes) are in Table The cross-tabulation, bleeding gums versus POAG, is in Table The cross-tabulation, loose teeth versus POAG, showed that 0.6% of the subjects without loose teeth had POAG and that 0.8% of the subjects with loose teeth had POAG . The cross-tabulation, dentures versus POAG, also showed that 0.60% of the subjects without dentures had POAG and that 1% of the subjects with dentures had POAG . The effect of toothache on POAG was insignificant . The relationship of tooth problems to POAG has been reported previously .The corneal-compensated IOP of the left eye in 67,152 subjects without bleeding gums was 16.11 ± 4.28 and in 12,469 subjects with bleeding gums was 15.95 ± 4.41 . Age-weighted least-squares linear regression was performed. The corneal-compensated IOP of the left eye was the dependent variable, and bleeding gums (no/yes), past smoking (no/yes), and type 2 diabetes (no/yes) were the independent variables. Bleeding gums were significantly correlated with lower IOP  and independent of the effects of type 2 diabetes  and past smoking .Table The cross-tabulation, bleeding gums versus AD, is in Table Logistic regression and 95% confidence interval (CI) lower bound (LB) and upper bound (UB) of AD (no/yes) (dependent variable) and bleeding gums (no/yes), age, and sex (independent variables) are shown in Table There was no direct relationship between POAG and AD . Other studies have reported the same lack of relationship, as noted above -7.A “yes” answer to a question about bleeding gums is associated with a greater proportional POAG reduction (24.2%) than a “no” answer (6.3%). The corneal-compensated left eye IOP difference in subjects with versus without bleeding gums was statistically significant, but the effect size was quite small. While clinically insignificant, the small effect size may indicate that bleeding gums are elaborating only a small amount of the substance or substances favorably affecting POAG and AD. If these substances could be identified and larger amounts administered, the effect size could be clinically significant.Porphyromonas gingivalis, a keystone pathobiont in periodontitis, and Bacteroides forsythus and their bacterial components have been found in the brains of patients with AD and seem to provoke the inflammation that is a feature of AD [Porphyromonas gingivalis on the enhancement of amyloid production and possible tangling of Tau proteins in Alzheimer’s disease [The protective effect of bleeding gums against POAG and AD is probably not due to bacteria. The major periodontal pathogens re of AD . There i disease ,20.POAG pathophysiology is influenced by the oral microbiome. Experiments in animal models suggest that higher bacterial loads can cause neurodegeneration by activating microglia in the retina and optic nerve, mediated by toll-like receptor 4 (TLR4) signaling and complement overexpression .Cytokines, such as interleukin-1 and tumor necrosis factor, and chemokines are produced during periodontal inflammation . HoweverProstaglandins are a key component of periodontitis and stimulate bone destruction by activating matrix metalloproteinases . HoweverA limitation in our analysis includes having different variables in Table Having none of the listed mouth conditions is associated with a lower incidence of POAG; in other words, mouth conditions, in general, predispose to POAG. Mouth ulcers are associated with a lower incidence of POAG, suggesting that mouth ulcers may elaborate the same POAG/AD protective substance or substances as bleeding gums. Alternately, the lower incidence of POAG in subjects with bleeding gums may result from some of these individuals ingesting something such as aspirin, which is known to cause bleeding gums  and is sIt is difficult to predict what component or components of bleeding gums or periodontal inflammation might be ameliorating POAG and AD, although prostaglandins are prime candidates. Conclusive identification of the component or components could lead to new treatments for POAG and AD. Prostaglandins are already known to be beneficial for POAG, but their effect on AD is not well established. New treatments for AD are sorely needed, and prostaglandins might be one. Further studies are warranted.


There is increasing awareness of the importance of patient activation  among clinicians and policy makers, with emerging evidence showing higher levels of patient activation are associated with better health outcomes and experiences of health care. This study aimed to examine the association between patient activation and a wide range of specific types of healthcare service utilisation in England, including GP and non-GP primary care, elective and emergency hospital admissions, outpatient visits, and attendances at the Accident and Emergency department.Data were derived from linked electronic patient records collected by primary and secondary healthcare providers in North West London between January 2016 and November 2019. Our analyses focused on adults (18+) with a valid Patient Activation Measure (PAM). After excluding patients with missing data, we had an analytical sample of 15,877 patients. Data were analysed using negative binomial regression and logistic regression models depending on the outcome variable.Patients had a mean activation score of 55.1 and a standard deviation (SD) of 17.7 (range: 0–100). They had an average of 5.4 GP visits (SD = 8.0), 26.8 non-GP visits (SD = 23.4) and 6.0 outpatient attendances (SD = 7.9) within a one-year follow-up. About 24.7% patients had at least one elective admission, 24.2% had one or more emergency admissions, and 42.3% had one or more A&E attendance within the follow-up. After accounting for a number of demographic and health factors, we found a linear (or proximately linear) association between patient activation and the number of GP visits, emergency admissions and A&E attendance, but a non-linear relationship between patient activation and the number of non-GP visits, the number of outpatient attendance and elective inpatient admission.This study has provided strong empirical evidence from England linking patient activation with healthcare service utilisation. It suggests the value of supporting patient activation as a potential pathway to ease the burden of healthcare system.The online version contains supplementary material available at 10.1186/s12913-021-07115-7. Patient activation describes an individual’s knowledge, skills, and confidence for managing his/her health and health care . PatientIn addition, there is also some evidence suggesting that higher levels of patient activation are related to lower healthcare utilisation and costs , 6, 9–12To our knowledge, there is only one pervious study that examined the association between patient activation and healthcare utilisation using data from the UK. It found that patients with a higher level of activation had a lower healthcare utilisation in general and less wasteful use . HoweverN = 19,891 patients). We excluded patients with less than one-year follow-up since their assessments (5%) and patients with missing values in any core demographic and health covariates (16%). The excluded patients due to missing covariates had similar PAM as the analytical sample  reside. The dashboard provides real-time detailed information on how patients access and use health and social care services. We used data collected since January 2016 when PAM were introduced and patients were followed up until November 2019. Our analyses focused on adults (age 18+) who had undergone an assessment of their patient activation levels . Both were treated as count variables derived from logged administrative records. For admitted patient care, we made a distinction between emergency and elective admissions. These were coded as binary variables indicating if patients had any emergency or elective admission respectively during the one-year follow-up. For outpatient care, we examined the number of outpatient attendances as a count variable and non-attendance as a binary variable, indicating if patients had missed any appointment. Finally, A&E attendance was coded as a binary variable, indicating if patients used A&E service within the follow-up period.In the analyses, we controlled for a number of demographic and health covariates, including age , gender (women vs men), ethnicity , area deprivation (measured by the index of multiple deprivation quantiles) and existing long-term physical and mental health conditions .The count outcomes  were analysed using negative binomial regression models to account for over-dispersion. The binary outcomes  were analysed using binary logistic regression models. In both set of models, we tested quadratic terms of PAM to assess the possibility of non-linearity. All analyses were adjusted for covariates identified above and conducted using Stata V15.Patients included in our analysis had a mean PAM score of 55.1 and a standard deviation (SD) of 17.7. There were 27.8% patients at the lowest activation level (level 1), another 27.8% at level 2, 30.0% at level 3 and 14.3% at the highest activation level (level 4). Within the one-year follow-up, patients had an average of 5.4 GP visits (SD = 8.0) and 26.8 other non-GP primary care contacts (SD = 23.4). There were 24.7% patients having had at least one elective admission within the follow-up, and 24.2% having had one or more emergency admissions. On average, patients used outpatient services 6.0 times (SD = 7.9). About 34.3% patients had at least one outpatient appointment. Finally, 42.3% patients had one or more A&E attendance within the one-year follow-up period. For descriptive statistics of demographic and health covariates, please see Table SFigure As shown in Fig. The predicted probabilities of elective hospital admission with 95% CIs are presented in Fig. As shown in Fig. As shown in Fig. N = 20). The estimates of our main variable of interest, PAM, were largely the same  care, admitted patient care (elective and emergency admissions), outpatient and A&E attendance. However, the associations between patient activation and healthcare service utilisation varied depending on the specific service, suggesting a complex interplay between patient activation and both patient health needs and health behaviours.As expected, patients who were more active in managing their health conditions made less use of GP services, emergency admitted patient care and A&E services compared with their less active counterparts. This is consistent with previous studies conducted in other countries , 6, 10 aHowever, the relationship was non-linear for other healthcare services, namely non-GP consultation, elective inpatient admission and outpatient care. For these healthcare services, service utilisation decreased with patient activation within higher PAM levels, but increased as patient activation increased at lower levels. It is possible that for patients at lower activation levels, lower usage could be a result of denial or lack of recognition of symptoms that require early intervention. In contrast, an increased use in these services is a reflection of better health self-management, such as regular check-ups, preventive screening, adherence to treatments and so forth. These services are relatively less resource intensive and costly compared to other emergency healthcare services . TherefoThis study has the advantage of using large scale administrative records of both primary and secondary health care and examining a wide range of healthcare services. However, it is not without limitations. First of all, this is an observational study, which is not sufficient to establish causality. We have controlled for a number of demographic and health factors, but any confounding risks by unmeasured variables cannot be ruled out. Secondly, although we examined the relationship between patient activation and subsequent service utilisations after the PAM assessment, this is a cross-sectional research design in nature. Further longitudinal investigation is recommended to understand how change in patient activation is related to change in healthcare service utilisation. Finally, our data were from London only. It remains to be explored if similar results would be found in other regions or countries in the UK.Overall, this study has provided strong empirical evidence linking patient activation with the uptake of different types of healthcare services using data from England. It suggests the importance of measuring patient activation as a way of understanding behavioural patterns relating to healthcare service utilisation. It additionally supports the value of testing whether increasing patient activation could be a potential pathway to ease the burden of healthcare system through interventions such as health coaching, peer support, self-management education and so forth –18. FinaAdditional file 1: Table S1. Descriptive statistics comparing the analytical sample with excluded patients due to missing data. Table S2. Descriptive statistics . Table S3. Results from negative binomial regression models. Table S4. Results from logistic regression models. Table S5. Results from negative binomial regression models: multiple imputation. Table S6. Results from logistic regression models: multiple imputation.


Accurate prognostic markers are urgently needed to identify diffuse large B-Cell lymphoma (DLBCL) patients at high risk of progression or relapse. Our purpose was to investigate the potential added value of baseline radiomics features to the international prognostic index (IPI) in predicting outcome after first-line treatment.Three hundred seventeen newly diagnosed DLBCL patients were included. Lesions were delineated using a semi-automated segmentation method , and 490 radiomics features were extracted. We used logistic regression with backward feature selection to predict 2-year time to progression (TTP). The area under the curve (AUC) of the receiver operator characteristic curve was calculated to assess model performance. High-risk groups were defined based on prevalence of events; diagnostic performance was assessed using positive and negative predictive values.peak and the maximal distance between the largest lesion and any other lesion . Combining radiomics and clinical features showed that a combination of tumor-  and patient-related parameters (WHO performance status and age > 60 years) performed best (AUC 0.79). Adding radiomics features to clinical predictors increased PPV with 15%, with more accurate selection of high-risk patients compared to the IPI model .The IPI model yielded an AUC of 0.68. The optimal radiomics model comprised the natural logarithms of metabolic tumor volume (MTV) and of SUVPrediction models using baseline radiomics combined with currently used clinical predictors identify patients at risk of relapse at baseline and significantly improved model performance.EudraCT: 2006–005,174-42, 01–08-2008.The online version contains supplementary material available at 10.1007/s00259-021-05480-3. Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of aggressive non-Hodgkin lymphoma (NHL) in adults. Up to one third of these patients fail to achieve complete remission during first-line treatment or experience relapse, and salvage treatment regimens lead to modest cure rates , 2. Iden18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters, especially baseline metabolic tumor volume (MTV), have shown to be predictive of outcome in DLBCL [18F-FDG-avid tumor burden, but it does not comprise phenotypical aspects like spatial distribution, heterogeneity, and shape of lesions. Recently developed quantitative 18F-FDG PET image features, also referred to as radiomics, reveal biological characteristics of disease and could help to improve outcome prediction in DLBCL at baseline. Radiomics features capture detailed and quantitative information on, e.g., texture and shape of lesions. In several solid tumors, radiomics features provide prognostically relevant information [Quantitative in DLBCL –9. MTV rormation –13. Evidormation , 15. How18F-FDG PET/computed tomography  were included in this study. 18F-FDG PET/CT scans were included from 58 different hospitals. Main inclusion and exclusion criteria of the trial have been published elsewhere [Newly diagnosed DLBCL patients from the multicenter randomized phase 3 HOVON-84 trial  who underwent baseline lsewhere . As ther18F-FDG PET/CT scans were centrally collected from participating sites in DICOM format and de-identified. For quality control (QC), we used criteria described by EANM guidelines: mean standardized uptake value (SUVmean) of the liver should be between 1.3 and 3.0 and the plasma glucose lower than 11 mmol/L [mean was outside the acceptable ranges, and the total image activity (MBq) was not between 50 and 80% of the total injected FDG activity or (4) plasma glucose exceeded 11 mmol/L.Baseline 1 mmol/L . QC reje18F-FDG-avid structures defined by a SUV ≥ 4.0 and a volume threshold of ≥ 3 mL. Non-tumor regions were deleted, and lymphoma lesions < 3 mL were added with single mouse clicks. If tumor regions were adjacent to non-tumor 18F-FDG-avid regions , non-tumor regions were removed manually. Details on the delineation methods and workflow are described elsewhere [Quantitative PET/CT analysis was performed using the ACCURATE tool . Lesionslsewhere , 20. Allmax, SUVpeak, SUVmean, and total lesion glycolysis (Four hundred eighty features pertaining to morphology n = 22), intensity (n = 50), and texture (n = 408)  were extycolysis . All ima, intensipatient), the distance between the largest lesion and the lesion furthest from that bulk (Dmaxbulk), the sum of the distances from the largest lesion to all other lesions (spreadbulk), and the sum of the distances from all lesions to all the other lesions (spreadpatient). Distances were calculated based on the location of the SUVmax for each lesion.The patient level VOI included all segmented lesions and was generated by assigning all voxels within the individual lesions to one and all voxels outside any of the segmented individual lesions to zero. At patient level, 5 conventional PET features and 5 dissemination features were extracted: the number of lesions and 4 features as suggested by Cottereau et al. , the disFor the currently used clinical predictors, the IPI score , the indThe primary endpoint was 2-year time to progression (TTP), defined as time from baseline PET/CT to progression. Patients who died without progression were censored at date of death. Patients still alive were censored at date of last contact.Model 1. IPIModel 2. Clinical modelModel 3. MTV at patient levelModel 4. Limited radiomics model: conventional PET, dissemination, and sphericity features  at patient levelModel 5. All radiomics features for the largest and hottest lesions, respectivelyModel 6. Combination of the clinical predictors (model 2) and radiomics features (model 4) Table The predictive value of the following models was assessed:To evaluate model performance for 2-year TTP, the receiver operator characteristic curve was generated to calculate the area under the curve (AUC). A 95% confidence interval (CI) of the AUC and differences between model performances of prediction models, expressed as AUC, were assessed with the two-sided DeLong test . StratifFor all models except model 5, multivariate logistic regression with backward selection was used to predict outcome. For models 4 and 6, to reduce the radiomics feature space dimension, the previously reported features regarding intensity, volume, shape, and dissemination of the lesions were preselected . For modSurvival curves were obtained with Kaplan–Meier (KM) analyses for TTP and compared with log-rank tests for the IPI, best clinical, MTV, best radiomics, and best combined prediction models based on logistic regression. In our dataset, 16% of all patients had progression at 2-year TTP, so for each model, 16% of the patients with the highest risk were included in the high-risk group for all KM survival plots except for the IPI KM survival plot, for which we used the high-risk IPI group as high-risk group. Univariate Cox regression models were used to calculate hazard ratio’s (HR) and their corresponding 95% confidence intervals. The assumption of proportional hazards was assessed based on Schoenfeld residuals.p value of less than 0.05 was considered statistically significant.Statistical analysis was performed using R (version 4.0.0). A Three hundred seventy-three patients had a baseline PET/CT, of which 317 were included in this analysis. The main reason for ineligibility was missing essential DICOM information n = 21). Other reasons for exclusion were QC outside of range (n = 19), incomplete whole-body or total-body PET/CT scans (n = 13), no FDG-avid lesions (n = 2), and plasma glucose out of range (n = 1). Clinical characteristics of included patients are summarized in Table 1. Other patient, Dmaxbulk, Spreadpatient, Spreadbulk) were higher for patients with an event within 2 years .Per patient, 1–143 lesions were analyzed, with a median of 19 lesions per patient for patients who experienced relapse or progression within 2 years and a median of 8 lesions for patients without relapse. The median MTV was 652.2 mL for patients with an event within 2 years and 351.4 mL for patients without relapse. All dissemination features  was significantly associated with outcome (p < 0.001), yielding an AUC of 0.68  , WHO performance status ≥ 1 (p = 0.026), and EN involvement ≥ 1 (p = 0.039) were all significantly associated with 2-year TTP, and together yielded an AUC of 0.73 . This was not significantly higher than the discriminative power of IPI (model 1) (p = 0.267).75) Fig. , Table 4MTV (model 3) was significantly associated with outcome (p < 0.001), yielding an AUC of 0.66 . The natural logarithms of MTV (p < 0.001) and of SUVpeak (p < 0.001) and Dmaxbulk (p = 0.001) were all significantly associated with 2-year TTP, and together yielded an AUC of 0.76  for the limited radiomics model (model 4) using logistic regression with backward selection. When correcting Dmaxbulk for height, the radiomics model still yielded in an AUC of 0.76. This model showed a trend for better discriminative power compared to the IPI prediction model  but was significantly higher than the discriminative power of MTV only . LASSO regression with all radiomics features yielded a CV-AUC of 0.67 for the largest lesion and a CV-AUC of 0.54 for the hottest lesion (model 5). For both models, texture features have contributed most to the model  and of SUVpeak (p < 0.001), Dmaxbulk (p = 0.002), WHO performance status ≥ 1 (p = 0.044), and age > 60 (p = 0.045) were all significantly associated with 2-year TTP, and together yielded an AUC of 0.79  in a multivariate model. This combination showed better discriminative power compared to the IPI model  and the best clinical prediction model  and a trend for better discriminative power than the best radiomics prediction model . Model performances and feature selection using LASSO regression for model 1–4 and 6 are presented in the Supplemental data , the natural logarithms of MTV . For all prediction models, AUCs with 2-year PFS as outcome parameter were lower compared to AUCs with 2-year TTP as outcome parameter  had higher discriminative power compared to the IPI prediction model  of an event was 16%. By selecting high-risk patients with our combined prediction model, the posterior probability  of an event in this group increased to 44%. There are more high-risk patients included in the high-risk group identified using radiomics features combined with clinical parameters compared to the IPI model, as shown by higher progression rate at 2-year TTP . These survival rates are still rather high, meaning that even the best model poorly identifies real high-risk patients; this may be partly caused by our choice of outcome parameter. We chose TTP instead of the more commonly used PFS and overall survival (OS), because unlike TTP, both PFS and OS are affected by age [Radiomics features could increase the efficiency of the design of future clinical trials for new therapies. By only selecting the high-risk patients according to our proposed prediction model, fewer patients that will not experience an event will be included. Since about 44% of the patients will experience progression, depending on the expected effectivity of the proposed drug, the difference between standard and new therapies can be studied under optimal power conditions. This allows for smaller sample sizes and thus lower costs.MTV is one of the most studied radiomics features in DLBCL –9, 27. IRelatively few studies have investigated the predictive value of other radiomics features in DLBCL. Moreover, due to the different features that were extracted and different numbers of features extracted, it is hard to perform a direct comparison between studies. Generally speaking, our results confirm the findings of Parvez et al., who found that radiomics features of the hottest lesion have limited predictive value . Aide etpatient and Dmaxbulk were significantly associated with outcome and that Dmaxpatient was the only predictor of outcome in multivariate analysis. In our analysis, the predictive performance of Dmaxpatient and Dmaxbulk was similar, but the discriminative power for Dmaxbulk exceeded that of Dmaxpatient, so that Dmaxpatient was not included in our multivariate model with backward selection. We found that adding Dmaxbulk and SUVpeak to MTV significantly improved model performance (raising AUC from 0.66 to 0.76).Cottereau et al.  were the18F-FDG PET/CTs are already part of clinical practice; therefore, radiomics features can be calculated at no additional costs. With software becoming available that easily and reliably calculate radiomics features [Risk stratification significantly improved when combining radiomics features with clinical parameters , 31, 32.features , adding features , 35. HowThis study is the first to investigate the predictive value of radiomics features at patient level, for the largest lesion and the hottest lesion while combining it with currently used clinical predictors, making it the most comprehensive study so far. Even though this is the largest study that examined the predictive value of radiomics features, with 18% of the patients that were included in the prediction model having progression, this study had limited power to test more complex prediction models that included more features or to make a distinction between refractory patients and relapsed patients. Another limitation of this study is that we used a single method to segment the lymphoma lesions. Due to the large heterogeneity of tracer uptake in DLBCL lesions, choosing a single segmentation method for the whole cohort could have caused suboptimal segmentation of lesions for some patients. However, literature suggests that the fixed SUV4.0 segmentation method is successful in 78% of DLBCL patients without editing and is acceptable in 98% of patients after manual editing . Moreovehttps://petralymphoma.org). Moreover, the combination of radiomics and genomic features could be investigated, since both have promising results, and by combining these biomarkers, the identification of high-risk DLBCL patients could be further improved.To further investigate the predictive value of radiomics features in DLBCL, these results will be validated in a large cohort of DLBCL patients treated in different clinical trials Below is the link to the electronic supplementary material.


Cardiac rehabilitation (CR) can improve clinical indicators in patients with cardiovascular diseases. The literature reports a 20% reduction in all-cause mortality and a 27% reduction in heart-disease mortality following CR. Although its clinical efficacy has been established, there is uncertainty whether center-based (CBCR) is more effective than home-based (HBCR) programs in acute and subacute phases. We aimed to verify significant differences in their effectiveness for the improvement of cardiopulmonary function by analyzing cardiopulmonary exercise (CPX) with laboratory tests following both CR programs.A single-center cohort study of 37 patients, recently diagnosed with underlying cardiovascular diseases, underwent CBCR(18) and HBCR(19). CBCR group performed a supervised exercise regimen at the CR center, for 1 hour, 2 to 3 days a week, for a total of 12 to18 weeks. HBCR group completed a self-monitored exercise program at home under the same guidelines as CBCR. Participants were evaluated by CPX with laboratory tests at 1- and 6-month, following the respective programs.P < .05). CBCR approach showed greater improvement with significance in VO2/kg, metabolic equivalents, and EF on between groups analysis (P < .05).There was no statistical significance in clinical characteristics and laboratory findings. Pre–post treatment comparison showed significant improvement in VO2/kg, minute ventilation/carbon dioxide production slope, breathing reserve, tidal volume (VT), heart rate recovery, oxygen consumption per heart rate, low-density lipoprotein (LDL), LDL/HDL ratio, total cholesterol, ejection fraction (EF) (The time effect of CPX test and laboratory data showed improvement in cardiopulmonary function and serum indicators for both groups. VO2/kg, metabolic equivalents, and EF were among the variables that showed significant differences between groups. In the acute and subacute phases of 1 to 6 months, the CBCR group showed a greater cardiac output improvement than the HBCR group. The literature reports that patients with ischemic heart disease (IHD) receiving CR have a 20% and 27% reduction in all-cause and heart-disease-related mortalities, respectively.,4 A Cochrane review of 147 studies demonstrated that, for myocardial infarction and heart failure, cardiovascular mortality and readmission rates were reduced by 25% and by 20%, respectively.,6 A meta-analysis by Kabboul in 2018 compared the effects of core components of CR on morbidity and mortality, thereby showing a significant reduction in all-cause mortality.Cardiac rehabilitation (CR) is associated with many benefits, including improved quality of life, psychosocial well-being, and cardiorespiratory fitness. The reasons include the lack of programs across centers worldwide and low referral rates compounded by transportation and cost barriers.–12Despite current international guidelines promoted by the American Heart Association and the European Society of Cardiology, among others, CR is significantly at a global minimum with varying rates. with clinicians and medical centers’ collaborative efforts by appropriately promoting CR to patients at the bedside.However, these variables can be mitigated The incentive for pursuing the study stemmed from the need for CR among cardiac postsurgical patients who lived in remote rural areas, where center-based (CBCR) programs were nonexistent. Since then, studies throughout the literature have similarly reported that HBCR showed improvement of relevant symptoms and clinically meaningful indicators.Traditionally CR programs have been medical center-based and conducted in an outpatient setting under medically trained and licensed specialists. Home-based cardiac rehabilitation (HBCR) was first introduced in North America and Italy. One study—a nonrandomized controlled quasi-experimental investigation—based out of Italy  paved the path for standardizing underlying principles of a home-based approach to CR.However, few studies have analyzed clinically important cardiopulmonary function indices and other secondary preventive variables by comparing CBCR versus HBCR. There are no published data showing significant differences between outcome variables in CBCR and HBCR programs overall. Furthermore, no studies have compared cardiopulmonary exercise (CPX) and laboratory test results simultaneously. The knowledge gap herein is worthy of focused investigation. Our study aimed to verify significant differences in CPX and laboratory data's clinical measurements by comparing CBCR with HBCR, between 1- and 6-month following respective CR programs.22.1The study protocol was reviewed and approved by the Ethic's Committee of Myogji Hospital (IRB# MJH2020-05-010). A convenient sample of 121 IHD survivors , previously evaluated at our CR center, were recruited. All patients underwent indicated procedures—percutaneous coronary intervention or coronary artery bypass graft—during their inpatient course in cardiology. Our inclusion criteria were as follows: IHD survivors, participants of CR, all CR patients treated from November 2018 to April 2020. The exclusion criteria were: severe heart failure, unstable angina, uncontrolled arrhythmia, history of major psychiatric illness, other significant noncardiac-related comorbidity, precluding the ability to exercise on the treadmill, readmission for subsequent acute myocardial infarction with previous intervention received. These criteria are based on the CHARMS randomized trial by Dalal in 2007 of participants who underwent prescribed “home” or “center”-based CR following IHD.2.2The study aimed to compare clinical outcomes of CPX indices and laboratory data from the 2 interventional approaches, CBCR versus HBCR programs. The investigation is a retrospective, nonrandomized, nonblinded controlled study design by analyzing patients’ medical records at our institution upon referral for CR from other departments in our medical center. CR specialists—physicians and nurses—interviewed patients to determine their suitability for CR. Patients and their family members were educated on cardiac disease risk factors, emphasizing the importance of lifestyle modification to achieve beneficial results. The selection process is summarized in Figure The sample size was determined to yield a moderate effect size with a power of 0.80. Among the initial recruits having met eligibility criteria, 47 were eliminated following initial CPX evaluation performed at 1- and 6-month status post CR referral. Laboratories were drawn at 1- and 6-month after enrollment. Thereafter, 37 patients were further eliminated for various reasons based on eligibility criteria, including losses to follow-up. The final study population of 37 was selected for full participation in the study. Participants were allocated to either CBCR or HBCR groups. This was determined according to subjective preferences based on residential location and current lifestyle. The same guidelines (ACSM-2006) were applied to both groups to prescribe the exercise program.2.3 The CPX test was completed in our study following the American College of Cardiology/American Heart Association guidelines. The instrumentation for testing consisted of a Treadmill and Recumbent system (Appendix 1).The validity and reliability of CPX testing have been substantiated by Nieman et al in 2013 and are outlined in their work assessing energy metabolism during aerobic exercise in healthy subjects.2.4Labs were drawn by diagnostic laboratory and analyzed by an automated chemistry analyzer (Appendix 2); these included high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and creatine (Cr). The ejection fraction (EF) was measured by a cardiologist using portable ultrasound machines at our institution (Appendix 3). The resultant data were uploaded onto the EMR system.2.5The initial discharge planning incorporated an orientation program involving a health education session for all patients regarding their underlying conditions.Risk factor modifications and adherence to the prescribed program with their benefits were emphasized to enhance attendance and compliance rates. The applied intensity was based on a target heart rate range using the Karvonen formula. ACSM guidelines also recommend that during exercise, patients should: pay close attention to the difficulty level of the work rate, and this should subjectively reflect the total amount of exertion and fatigue, combining all sense of physical stress effort and fatigue. Guidelines suggest that light-to-moderate intensity (RPE of 11–14) is suitable for cardiac patients and that it is essential to use standardized instruction to minimize misinterpretation of RPE.The initial evaluation involved CPX and laboratory testing regardless of preferred group selection. The prescribed exercise intensity was calculated based on the heart rate reserve achieved during the preliminary graded exercise testing and the rating of perceived exertion (RPE) based on ACSM-2006 guidelines.2.6Participants in the CBCR group attended outpatient sessions once or twice weekly for 18 to 24 weeks. These sessions included providing feedback on their progress, condition, and education on ongoing lifestyle habits. The outpatient CBCR program's initial stage involved reviewing medical history, diagnosis, medications, lab results, pain symptoms, and pertinent risk factors. We used the cardiac rehab center's instrumentation system (Appendix 4); participants were reeducated on the exercise program's method, purpose, precautions, and other procedure-relevant details.2.7 Healthy lifestyle education with pertinent information on the prescribed home program is reiterated at discharge. Participants were advised to adhere to the specified home program for 12 weeks before returning for the follow-up. The intensity level was adapted to the speed at which the participant previously achieved on the treadmill during the inpatient training.The home program, primarily focused on brisk walking, is suggested as the preferred activity sufficient to increase aerobic capacity in healthy sedentary and cardiac patients.Participants were advised to contact the center for necessary guidance during home participation. Their exercise log was reviewed every 15 days. When any subjective concerns were reported, trained physiotherapists provided detailed instructions, particularly concerning signs and symptoms during the performance. When necessary, criteria for termination of activity were also explained as per ASCM Guidelines.2.8t test were used to compare participants’ baseline characteristics, and descriptive statistics included the means with standard deviations.Chi-square test and independent P < .05. Statistical Package for the Social Science, Windows v25.0, was used for all statistical analyses.A “Groups” (CBCR and HBCR) × “Times” (1- and 6-month) repeated measure by ANOVA was used to determine the statistical difference in CPX variables . Group × Time's significant interaction would indicate that the observed change between 1- and 6-month intervals is significantly different between CBCR and HBCR groups. Tukey post-hoc test was performed if the interaction and main effects were observed. Laboratory data  at both time-intervals for the groups were included in the comparative analysis, and statistical significance was set at 3t tests did not show significant differences in the baseline demographic and clinical characteristics between the 2 groups , METs (P < .001), VE/VCO2 slope (P = .023), BR (P = .003), tidal volume (VT) (P = .013), HRR (P = .001), VO2/HR (P = .031), LDL (P < .001), LDL/HDL ratio (P < .001), total cholesterol (P < .001), EF (P = .005) respectively. In addition, VO2/kg, METs, and EF improved in the CBCR group compared with the HBCR group on between groups analysis (P < .05)  . The increase in CBCR was marginally greater than HBCR (P = .047). Contrary to our observations, Park's study in 2019 found no significant differences in VO2max between groups. A systematic review by Blair et al in 2010 showed improvement in 6-minute walk test, physical daily activity index, functional capacity, and estimated VO2 in both groups with minimal and no difference between groups. These results can often be affected by patients’ motivation and subjective preferences of measurements conceptualized in the study design by trialists. HBCR participants in our study, who had poor motivation for participation, showed a significant difference in oxygen intake compared with the CBCR group.We observed a significant increase in VO2/kg for both groups compared at 1- and 6-month . CBCR participants have the advantage of being monitored during exercise performance; thus, they are more motivated to participate. HBCR participants require a scheduled visit or phone call to assess their interim progress. The different circumstances can easily be a source of discouragement, thereby minimizing willingness or motivation to participate, especially when performing independently at home.[METs] METs is an objective measure of the rate at which one expends the energy level relative to their weight while performing a specific activity. One MET is defined as the amount of oxygen consumed during rest and is equivalent to 3.5 mL/kg/min.P = .023, P = .922). In the CBCR group, 11 out of 18 participants had a 34 or greater slope at 1 month.[VE/VCO2] The VE/VCO2 slope is the minute ventilation/carbon dioxide production, indicating ventilatory efficiency. The slope decreased significantly between 1- and 6-month in both groups and without significant difference between groups , the VE/VCO2 slope's diagnostic odds ratio was reported to be 5.40 and that there was a stronger association with mortality than with peripheral venous blood gas and exercise duration. And thus, these variables were consequently identified as a robust prognostic predictor.If the VE/VCO2 slope is greater than 34, it indicates an abnormal response ventilatory inefficiency. Our study showed a significant decrease in BR for both groups (P = .003).[BR] Breathing reserve significantly increased from 1- to 6-month in both groups. BR (%) is defined as [(1−VEmax/VEmax predicted) × 100]. It is expressed as the difference between maximum exercise ventilation and maximal voluntary ventilation and a ventilatory response indicating the maximum breathing capacity during maximal exercise. In healthy men, BR is at least 10% to 40% of maximal voluntary ventilation. In the setting of lung disease, it is characterized by a low BR, whereas in cardiovascular disease, a high BR appears at a limited amount of exercise.P = .013). Molino-Lova et al in 2013 reported in their study the results of a 6-minute walk test before and after CR in the elderly. Patients who underwent median sternotomy showed to have an increase in VT with an increase in metabolic demand. In our study, the metabolic demand of the subjects increased due to the 6-month CR program. Since VT has been shown to increase following CR, inspiratory muscle training for enhancing ventilatory efficiency in IHD should be included in CR programs.[VT] The tidal volume (VT) increased significantly from 1- to 6-month in both groups (P = .001). HRR is defined as the heart rate, which decreases 1 minute after exercise. As indicated by Cole et al in 1999, a study of coronary heart disease (CHD) among a cohort of elderly patients reported being a strong predictor of mortality. They reported that change in HR after exercise was under the control of parasympathetic tone. In our study, both groups showed a significant increase in HRR (P = .001), indicating that parasympathetic regulatory function was improved after CR.[HRR and VO2/HR] Heart rate recovery showed a significant increase from 1- to 6-month in both groups (P = .031). VO2/HR (mL/min) is an oxygen pulse and follows the cardiac stroke volume during exercise. This coincides with the EF and shows a significant increase in cardiac output after CR in both groups. There was a significant difference between groups in EF (P = .028), but there was no significant difference between groups in VO2/HR (P = .199). This can be attributable to the difference in measurement methods between EF (ultrasound image) and VO2/HR .VO2/HR increased significantly between 1- and 6-month in both groups , and total cholesterol from 1- to 6-month (P < .0001). In a study by Natarajan et al in 2003, LDL/HDL ratio showed a better predictor of CHD risk reduction than HDL or LDL changes independently. Therefore, both CBCR and HBCR are sufficient to reduce the risk of CHD. These results collaboratively substantiate reports of decreased CHD and atherosclerosis risks in association with reduced LDL, LDL/HDL ratio, and total cholesterol levels.Lavie's study in 1994 showed improvement in HDL, LDL, LDL/HDL ratios, total cholesterol, triglycerides, body mass index, percent body fat, and METs following CR.P = .005). CBCR showed a greater increase with significance than HBCR (P = .028). In a study by Haddadzadeh in 2011, the changes in various indicators following a 12-week exercise program were assessed between CBCR, control group (nothing) (P = .003), and HBCR, control group (nothing) (P = .04). The resultant changes showed to be significant; however, there was no significant difference in the amount of EF change between CBCR and HBCR (P = 1.0). Haddadzadeh's study did not verify whether there was a difference in the EF from baseline. Although a significant difference from baseline EF was unobserved in our study, we confirmed the difference between CBCR and HBCR (P = .135). We observed a difference in VO2/kg between the CBCR and HBCR groups, and the change in EF supports this result.[EF] There was a time effect on EF with a significant increase for both groups . The results provide further evidence on CR's benefits toward efficient recovery of cardiac function among survivors of cardiovascular disease.The study confirmed that “time” effects of CPX improved cardiopulmonary function in both groups during the acute and subacute phases of recovery (1- and 6-month period) following CR. CBCR showed greater improvement than HBCR, in cardiac output with significance, in VO2/kg, METs, and EF on between groups analysis (The authors acknowledge Dr. Yong Gyun Kim for his valuable support, input, and guidance in this manuscript.Conceptualization: Jeong Jae Lee.Data curation: Jeong Jae Lee, Jun Young Ko.Investigation: Jeong Jae Lee.Methodology: Jun Young Ko.Project administration: Seungbok Lee.Resources: Jeong Jae Lee, Jun Young Ko.Software: Jeong Jae Lee.Supervision: Seungbok Lee.Validation: Seungbok Lee.Writing – original draft: Jeong Jae Lee.Writing – review & editing: Jun Young Ko, Seungbok Lee.


Plasmodium infection patterns in two low-endemic districts of Meghalaya was undertaken to better understand the epidemiology of malaria in northeast India.A detailed analysis of household and individual level Plasmodium falciparum and/or Plasmodium vivax infection using rapid diagnostic test, microscopy and PCR. Plasma samples from a subset of participants were analysed for antibodies against thirteen P. falciparum and four P. vivax antigens. Associations between household and individual level risk factors, and Plasmodium infections were evaluated using multilevel logistic regression models.Socio-demographic and behavioural information from residents (aged 1–69 years) of households were collected through pre-tested, questionnaire conducted in 2018 and 2019. Blood samples collected from participants were tested for P. falciparum in 2018 and none were positive for P. vivax. In 2019, no PCR-positive individuals were detected. All, but one, infections were asymptomatic; all 33 infections were sub-microscopic. Reported history of malaria in the past 12 months (OR = 8.84) and history of travel in the past 14 days (OR = 10.06) were significantly associated with Plasmodium infection. A significant trend of increased seropositivity with age was noted for all 17 antigens. Although adults (≥ 18 years) consistently had the highest seropositivity rates, a sizeable proportion of under-five children were also found to be seropositive. Almost all individuals (99.4%) reported sleeping under an insecticide-treated bed-net, and household indoor residual spray coverage in the 12 months preceding the survey was low (23%). Most participants correctly identified common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost all participants (94.3%) used government-provided services for treatment of malaria.A total of 2753 individuals from 827 households were enrolled in 2018, and 834 individuals from 222 households were enrolled in 2019. Of them, 33 (1.2%) were positive by PCR for Plasmodium transmission persists in this region. Implications of the study findings for malaria elimination efforts in low-transmission settings are discussed.This study explored the epidemiology of malaria in two communities in Meghalaya, India, in the context of declining transmission. The presence of widespread asymptomatic infections and seropositivity among under-five children suggest that low-level  Malaria continues to be a major public health problem globally with an estimated 229 million cases reported from 87 endemic countries . India hIn 2016, India launched the National Framework for Malaria Elimination with the ambitious goals of eliminating malaria from the country by 2030, maintaining malaria free status, and preventing reintroduction of infection in areas where transmission interruption has been achieved . To achiPlasmodium falciparum cases and 22% of the malaria deaths reported in 2019 [Even though the northeast region (NER) comprises about 4% of India’s population, it accounted for around 15% of the country's  in 2019 . This is in 2019 , 11. ThePlasmodium infection during 2018–2019 in 21 villages, summarised village-level risk factors for infection, and identified 13 Anopheles mosquito species as potential vectors in a subset of villages [Plasmodium infection patterns in the same two low-endemic communities in 2018–2019, evaluated social and behavioural risk factors for infection, and explored patterns of Plasmodium antigen-specific antibodies in the population.Information on malaria patterns in Meghalaya is limited to unpublished government reports and a recent cross-sectional survey in two districts . The latvillages . To furtThis study was conducted in two districts of Meghalaya: West Khasi Hills (KH) and West Jaintia Hills (JH). Meghalaya is a hilly and mountainous state in northeast India, located between Assam and Bangladesh Fig. , with a Plasmodium infections , representation across primary health centres (PHC) and health sub-centres in the study area and location. A random sample of households from each village (selected based on probability proportion to size technique) were consented and enrolled. A household survey was administered to one resident of each participating household, usually the ‘head of household’ that included questions on family size, source of water supply, building materials for roofs and walls, presence of electricity, toilets, animals and malaria prevention methods . In addition, the household members were administered individual surveys during which they were asked mostly close-ended questions in their local language  to obtain information on age, gender, education, occupation, knowledge of malaria, health history , travel history (past two weeks) and malaria prevention methods. Malaria risk behaviours and practices were also surveyed. Parents or caretakers responded on behalf of their children.Socio-demographic and behavioural information was collected from residents (aged 1–69 years) of households in the JH and KH from April to November 2018 and again from May to September 2019. Details of the sampling design and methods have been described elsewhere . BrieflyPlasmodium detection methods have been described elsewhere [P. falciparum and/or P. vivax infections was determined by a bivalent rapid diagnostic test  and an ultra-sensitive RDT (Abbott Alere). Blood smears were also collected, fixed in methanol and Giemsa-stained prior to qualitative and quantitative evaluation by light microscopy. From the small blood volume, blood components were separated by centrifugation into plasma and a red blood cell (RBC) pellet and stored at -80 °C until assayed.Details of the blood sample collection and lsewhere . BrieflyPlasmodium infections were detected by PCR amplification of concentrated DNA extracted from microvette RBC pellets using a single-step PCR targeting Pfr364  and Pvr47 (for P. vivax) genomes, respectively [Plasmodium infection was indicated based upon RDT results and/or PCR results; no infections were detected by microscopy.Species-specific ectively , as prevectively . A positP. falciparum and P. vivax proteins and/or peptides were coupled to unique Luminex Magplex magnetic microspheres and used in a multiplexed, bead-based assay to quantify host IgG antibodies as previously described [E. coli extract. All samples were assayed singularly with positive controls, naïve sample pools, and blanks run in duplicate or triplicate according to standardized procedures [Seventeen recombinant escribed . Plasma ocedures . Plates Plasmodium infection, along with the 95% confidence interval (CI), was calculated using the Taylor linearized method that accounts for the clustered data-structure [Plasmodium infections were evaluated using multilevel logistic regression models with exchangeable correlation matrix, considering village and household as grouping variables and reported as odds ratios (OR) with 95% CIs.Data were collected and managed using REDCap electronic data capture tools , 19 hosttructure . AssociaAg = raw MFIAg − background MFIAg) where background MFIAg is the mean MFI of a given antigen in the blank wells was calculated for each antigen in each sample assayed. The seropositive threshold for each antigen was defined as mean net MFInegative pool plus three standard deviations. The number and proportion of individuals seropositive for each antigen was tabulated for three age categories: children (1–7 years), adolescents (8–17 years), and adults (≥ 18 years). Differences in the proportion of seropositive individuals across the three age categories was determined by using the chi-square test for trend. The net MFIAg values from seropositive individuals were normalised with respect to the corresponding seropositive threshold value to generate a relative MFI value for comparison of response magnitudes . The median (IQR) relative MFI values were determined for each antigen across all age groups, and differences in the relative magnitude of response across age groups was tested using a nonparametric test for trend across ordered groups [Net mean fluorescence intensity (MFI) . Assent was obtained for participants aged 7–17 years, in addition to the parental consent.From 21 villages surveyed in JH (N = 9) and KH (N = 12) that represented 9306 residents from 1688 households, a total of 3017 (32.4%) individuals were approached for participation; 2753 individuals (29.6%) living in 820 households (48.6%) were enrolled in the study during 2018. In 2019, 222 households (13.2%) and 834 people (9%) from these villages were enrolled. The age and gender distribution of the total population of the two districts and that of the study participants is presented in Fig. P. falciparum; none of the participants tested positive for P. vivax. One (3%) of the 33 PCR-positive samples was also positive by RDT . The prevalence of P. falciparum infection was similar in JH  and KH . In 2019, none of 834 blood samples (0%) were positive for either Plasmodium species, including samples from 18 PCR-positive individuals from the 2018 survey. For this reason, analysis of risk factors for P. falciparum was undertaken solely for 2018.Blood from microvette samples during 2018 was available for testing from 1463 of the 1467 (99.7%) participants in JH, and 1234 of the 1286 (98.3%) KH participants. In 2018, 33 of 2697 study participants  were positive by PCR for The household level characteristics, aggregated by village, have been described elsewhere . BrieflyThe mean (SD) age of participants was 20.8 (17.2) years. Slightly more females (56.5%) than males participated in the study. Of the adult participants (≥ 18 years), a majority (47.6%) had less than primary education . Most participants were either students (35.8%) or engaged in agriculture-related activity (27.5%). Malaria diagnosis within the past 12 months was reported by only 3.6% of the participants; 2% of participants reported a history of travel outside of the village in the last 14 days. Around 5% of the participants reported staying in the field for one or more nights, with a mean (SD) of 6.9 (3.0) days. A large majority (86.2%) reported using ITNs while staying in the field. Most participants had knowledge of the common signs and symptoms of malaria, i.e., fever (96.4%), headache (71.2%), chills (83.2%) and body-ache (61.8%). Almost everyone (94.3%) preferred to seek treatment from government healthcare facility or community health worker , if diagnosed with malaria.The individual level socio-demographic characteristics of the study participants are presented in Table Plasmodium infections were assessed separately for JH and KH. A total of 2697 individuals from 819 households for whom a PCR-test result for Plasmodium infection was available were included in the analysis .The household and individual level risk factors for Plasmodium infection in individual household members  was significantly associated with Plasmodium infection in JH and history of travel in the past 14 days  was significantly associated with Plasmodium infection in KH. None of the other factors were significantly associated with risk of Plasmodium infection in either of the two study districts.The individual level risk factors for ed Table . A reporThe number and proportion of seropositive individuals in each age category are listed by antigen/antibody in Table P. falciparum antigens assayed: PfAMA1 (P < 0.001), PfEBA175 (P < 0.001), PfEBA181 (P = 0.001), PfEtramp5.Ag1 (P = 0.001), PfGlurp.R2 (P = 0.007), PfMSP119 (P < 0.001), PfRh2 2030 (P < 0.001), and PfRh5 (P = 0.011) (Table 19 (5.45), PfAMA1 (4.83), Rh2 2030 (4.74) and PfGlurp.R2 (4.72).The relative magnitude of antibody detected was significantly different across age groups for eight of the 13 1) Table . The relP. vivax antigens, PvAMA1 (P = 0.020) and PvMSP10 (P = 0.002). Independent of statistical significance, the relative magnitude of antibody was greatest in the adult age category for all four P. vivax targets with the highest relative MFI observed for PvAMA1 (5.04).The relative magnitude of antibody detected was significantly different across age groups for two of the four Questions about presence of mosquitoes and methods for reducing household level human exposure indicated widespread mosquito abundance and extensive efforts to decrease contact Table . MosquitIndividual level anti-mosquito protection was also widespread and appropriate Table . VirtualPlasmodium infection in the context of ongoing intensive malaria elimination effort in two districts of Meghalaya that only a few years ago had relatively high transmission [Plasmodium infection in the two communities in 2018 was determined, with malaria prevalence declining to essentially undetectable levels in 2019. Ninety-seven percent of the infected individuals had asymptomatic, sub-microscopic infection, which could only be detected through molecular (PCR-based) methods. A high prevalence of sub-microscopic infections was previously reported from malaria-endemic areas in India [Plasmodium infection [This community-based cross-sectional study investigated the prevalence, and household and individual level risk factors of malaria to better understand the epidemiology of smission . A low pin India –24 and ein India –27. As snfection , the usenfection .P. falciparum and four P. vivax antigens, chosen based upon prior classification as indicators of protection from clinical disease [Plasmodium transmission intensity [Plasmodium antigens in children under five years of age, however, can be considered as a marker of relatively recent exposure [Plasma samples from a subset of the study participants were analysed for presence of antibodies against thirteen  disease  or marke disease . The prontensity –35. The exposure  and provPlasmodium infection in this study. With increasing movement of people , imported malaria from cross-border and regional human movement represents a major obstacle to malaria elimination [A history of travel outside of the village within the past 14 days was associated with a higher risk of mination , 38, espmination  that shaP. falciparum infection in this study. Recurrent episodes of malaria occurring in a small percentage of individuals have earlier been reported from endemic areas [A reported history of malaria in the past 12 months was associated with a higher risk of ic areas –41. In aic areas . Mathemaic areas , 44. Theic areas –47 and eic areas , 48.P. falciparum and P. vivax malaria, respectively [Virtually every participant in the present study reported using ITNs. In a recent meta-analysis, ITN use was associated with 45% and 39% reduction in incidence of uncomplicated episodes of ectively . In anotectively . Also, nectively .Indoor residual spray coverage in the study districts was low, with only 23% of the households reported having been sprayed in the preceding 12 months, much less than the World Health Organization target of > 85% IRS coverage for preventing malaria transmission . Low levThe lack of understanding of what causes malaria, the use of ineffective prevention methods, the belief that malaria cannot be prevented, and general reliance on traditional remedies have been cited as major barriers to malaria prevention and treatment . In MeghPlasmodium-positive individuals resulted in reduced statistical power to evaluate the risk factors for infection in this population, which is a limitation of this study. Future studies in low-transmission settings may consider including serological markers of recent infection as a tool to estimate the burden and transmission patterns of malaria in low-intensity settings [Plasmodium infection prevalence may have been underestimated in this study. Finally, detailed exposure history could not be obtained for participants with serology results, which limited the ability to differentiate between recent and long-term exposure to Plasmodium infection.Despite enrolling more than 2500 participants, the low prevalence of settings . As withsettings , 65, thePlasmodium infections and the presence of anti-Plasmodium antibodies detected in children under five years of age suggests “hidden” transmission in the region, although the relative contribution of asymptomatic and sub-microscopic individuals to parasite transmission and/or clinical malaria in low-transmission settings need to be explored further. The higher infection risk observed among those with a travel history in a region with extensive international borders, heterogeneous distribution of Plasmodium infections, abundant vector populations, and favourable environmental conditions [This study provides important insights into the epidemiology of malaria in a low-transmission setting in India. The high proportion of asymptomatic nditions , 11 altonditions , 66. Con


Failed treatment of subtrochanteric fractures commonly leads to pain, limping, and poor limb function. Cementless total hip arthroplasty (THA) could serve as an efficient salvage procedure in such cases. This study aimed to evaluate the outcomes and complications of salvage THA in failed subtrochanteric fracture fixation cases.From January 2001 to December 2017, cementless THA for failed treatment of subtrochanteric fractures was performed in 18 hips of 11 men and 7 women . Patients were followed up for clinical and radiological assessments in terms of implant survival and complications after a minimum follow-up of 2 years. The Wagner femoral stems  were used in all 18 patients (100%), with the long-length stem (Wagner SL stem) and standard-length stem (Wagner cone stem) used in 11 and 7 patients, respectively.The mean follow-up period was 5.2 years (range: 2.2–10.8 years). The mean Harris hip score (HHS) was 38.2 (range: 24–56) preoperatively and 85.4 (range: 79–92) at the last follow-up. The mean postoperative limb length discrepancy was 6.4 mm (range: 4–9 mm). Only one patient underwent revision due to bone in-growth failure of the femoral stem. One patient had an episode of postoperative dislocation and was treated with closed reduction without reoccurrence. Delayed union of the fracture site occurred in one patient. Patients who were previously treated with an intramedullary nail had a significantly shorter surgical duration, lesser intraoperative blood loss, and fewer blood transfusions than those who were previously treated with plate and screws. Kaplan–Meier survival rate with an endpoint of revision was 94.4%  at 5 years.Our results indicate that cementless THA is a beneficial and effective procedure for salvaging the failed treatment of subtrochanteric fractures. The Wagner conical prosthesis has shown satisfactory function outcomes, stable fixation, and survival rate for these complex situations. However, attention should be paid to increased operation time, blood loss, and complications when performing THA for subtrochanteric fractures with failed fixation devices especially, plates and screws. Subtrochanteric fractures occur in the proximal femur between the inferior aspect of the lesser trochanter and a distance that extends approximately 5 cm distal to it. These types of fractures commonly occur in the younger population (severe comminuted and displaced fractures), caused by high energy impacts, as well as in the elderly population with osteoporosis, caused by low energy impacts . There are some successful treatments for subtrochanteric fractures that have been introduced in the past decades, including intramedullary fixation and extramedullary plates –3. HowevThe failure of subtrochanteric fracture treatment is frequently associated with unstable fracture patterns, poor bone quality, or suboptimal position of the fixation devices. Such complications following treatment failure may result in nonunion, leading to pain or malunion, severe bone defects, infection, articular cartilage damage, and even post-traumatic arthritis of the hip, which poses a significant challenge subsequent reoperation.Several salvage treatments can be performed for patients with failed treatment of subtrochanteric fracture, such as re-osteosynthesis  and prosHowever, to the best of our knowledge, few reports have described the results of cementless THA performed as a salvage therapy for failed subtrochanteric fracture fixation. Therefore, the purpose of this retrospective study was to evaluate the clinical outcomes, implant survival, rate of revision, and complications of salvage THA in failed subtrochanteric fracture fixation cases.The institutional review board of our hospital approved this retrospective study. Twenty-two hips of 22 patients with failed fixation of subtrochanteric fractures were treated at our institution between January 2001 and December 2017. One patient (one hip) was lost to follow-up, and three patients (three hips) died due to causes unrelated to THA before 2 years of follow-up; finally, 18 hips of 18 patients who were followed up for more than 2 years were included in this study. Before the operation, infection was preoperatively dismissed in all patients based on complete blood white cell count, total leukocyte count, erythrocyte sedimentation rate, and C-reactive protein levels. There were occurrences of fracture nonunion in all patients, which were related to metal failure in nine patients. In other patients, metal failures were related to metal breakage in eight patients and a cut-out screw in one patient. Prophylactic antibiotics were administered to all patients 30 min before the operation and continued postoperatively for 2 days. Patient demographic details are shown in Table All cases of fixation failures were treated using cementless THA by an experienced orthopedic surgeon. All THA procedures were performed using the posterolateral approach in lateral decubitus position. An additional skin incision was made or the original skin incision was extended to remove previously implanted fixation devices when necessary.After components reduction, the proximal fracture fragment was reattached to the proximal femur using a trochanter grip or a trochanter grip plate with cables , yielding good tension of the abductors and increasing the healing potential. In all cases, bone grafting was performed routinely for nonunion of the proximal femur using the femoral head. Postoperatively, a range of motion exercises and walking with limited weight-bearing was encouraged a day after surgery. Weight-bearing was gradually increased before obtaining radiological confirmation of bone union. Exercises for a range of hip motion and abductor strengthening were encouraged in all patients.Wagner straight conical femoral stems with rough blasting were designed for cementless fixation in severe bone deformity or dysplasia at the proximal femur. In our study, Wagner stems  were used in all 18 patients (100%), with the long-length stem (Wagner SL stem) and standard-length stem (Wagner cone stem) used in 11 and 7 patients, respectively. Details of acetabular cup and femoral components and additional devices are shown in Table After the operation, all cases were followed up after operation at 1, 3, 6, and 12 months for the first year and every 6 months after that. During the follow-up, ambulatory status and the Harris hip scores (HHS) were recorded. Postoperative radiographs were assessed routinely for prosthesis position and fixation. Limb length discrepancy was measured from radiographs at the last follow-up, using the method described by Woolson et al. . FemoralP < 0.5 was deemed significant. Survival of implants was analyzed using the Kaplan–Meier survival curve with 95% confidence intervals (CI). The starting point was the date of salvage THA and endpoint was the date of revision.Statistical analyses were performed using independent samples t-test or Mann-Whitney U test by the Statistical Package for Social Science (SPSS) software ; n = 8), a dynamic hip screw (n = 6), an angled blade plate (n = 2), a proximal femur locking plate (n = 1), or a dynamic compression plate (n = 1). All subtrochanteric femur fractures were classified based on the Orthopaedic Trauma Association (OTA) system and Russell–Taylor criteria. Among these 18 patients, 13 (72.2%), three (16.7%), and two (11.1%) had type A, B, and C fractures, respectively, based on the OTA classification system. According to the Russell–Taylor classification, subtrochanteric fractures were types 1A, 1B, 2A, and 2B in eight (44.4%), three (16.7%), four (22.2%), and three (16.7%) patients, respectively. The mean interval between primary fixation and salvage THA was 19.8 months (range: 4.7–53.8 months).The mean follow-up period was 5.2 years (range: 2.2–10.8 years). There were 11 men and 7 women, with an average age of 74 years (range: 57.0–89.0 years). At the time of previous internal fixation, the mean patient age was 72 years (range: 57.0–86.0 years). Several kinds of previous fracture fixations were used: a intramedullary nail . The mean total blood loss was 992.2 mL (range: 640–1260 mL), and the amount of blood transfused was 2.2 units (range: 1–4 units). The mean HHS was 38.2 (range: 24–56) preoperatively and 85.4 (range: 79–92) at the last follow-up. The mean postoperative HHS of patients with subsidence of stem was lower than that of patients without postoperative subsidence of stem, but it was not significantly different. The mean postoperative limb length discrepancy was 6.4 mm (range: 4–9 mm).Before the salvage operation, all cases (100%) had a walking disability; they had to use crutches because of hip pain. After the salvage THA, nine patients (50%) could walk without assistance, eight (44.4%) could walk using a cane, and one (5.6%) could walk using a single crutch. Subsidence of the stem occurred in nine patients (50.0%) 3 months after surgery. In this case series, the mean subsidence value was 3.4 mm in patients. One hip (5.6%) subsided more than 5 mm, which required stem revision; this case underwent previous intramedullary nailing refixation before conversion THA.In the group of patients previously treated with plate fixation, there were five cases with metal breakage of the device Fig. , whereasThe Kaplan–Meier survival analysis, with revision of the implant for any reason as the endpoint, revealed a survival rate of 94.4% (95% CI: 72.7–99.9) at 5 years Fig. . Only onComplications occurred in two of the 18 hips (11.1%). One patient had a postoperative dislocation and was treated by closed reduction with no reoccurrence. One patient showed delayed union of the proximal fracture site, which is defined as failure to reach bony union by 6 months after THA. No patients underwent reoperation even for the removal of trochanter grip or grip plate. For the cementless cups, no malposition or aseptic loosening was detected. There were two cases with class I heterotopic ossification and one patient with class II heterotopic ossification.Salvage treatment for failed subtrochanteric fracture fixation is challenging. Re-osteosynthesis with internal fixation or plates and conversion to hip replacement is accepted surgical salvage options. Elderly patients with metal failure of subtrochanteric fractures usually have poor bone quality in the proximal femur. In this situation, refixation will prolong their bed-rest period and prevent early ambulation, often necessitating replacement surgery . Some prSeveral authors have reported the results of THA in failed fixation of proximal femur fracture patients , 20, 21.In our series, we found that patients previously treated with an intramedullary nail had a significantly shorter surgical duration, lesser intraoperative blood loss, and fewer blood transfusions than those previously treated with plate and screws. We believe that intramedullary nails might be a better initial implant of choice for the treatment of subtrochanteric fractures, particularly as they can easily be converted to THA in cases of failure. When performing salvaged THA for subtrochanteric fracture with failed external plate fixation, we should pay special attention to increased operation duration, blood loss, and complications.Dislocation is another severe problem seen after the salvage procedure, often as a result of poor hip joint stability. Zhang et al.  reportedIn the present study, the Wagner femoral stems  were used in all patients. The Wagner conical stem is a tapered, fluted, grit-blasted cementless femoral prosthesis. This femoral stem was designed for treating complex primary THA or revision cases. Sandiford et al.  reportedSubsidence of the femoral stem could be a common complication in cementless stems and can lead to osseointegration failure, especially in complex THA. In this study, nine patients (50%) showed stem subsidence within 3 months of THA, but the amount of stem subsidence had no influence on clinical outcomes, such as thigh pain, HHS, or patient satisfaction. The subsidence rate observed in this cohort is comparable to previously reported rates of subsidence for femoral stems , 29. Of There are some limitations to this study. First, we did not set up a control group to compare the outcomes, and the study was retrospective. Second, there were a limited number of sample cases, and the follow-up duration was also relatively short. However, to the best of our knowledge, only two other studies have reported on more than 18 cases of failed THA for subtrochanteric fractures , 22 and Our results indicate that cementless THA is a beneficial and effective procedure for salvaging the failed treatment of subtrochanteric fractures. The Wagner conical prosthesis has shown satisfactory function outcomes, stable fixation, and survival rate for these complex situations. However, attention should be paid to increased operation time, blood loss, and complications when performing THA for subtrochanteric fractures with failed fixation devices especially, plates and screws. We believe that this report conveys valuable messages to surgeons who suffer technical difficulties following failed subtrochanteric femur fractures.