The purpose of this study is to systematically map all the factors that influence the fit and adaptation of zirconia crowns and/or copings.The investigational strategy involved carrying out an electronic search between December 1, 2009 and September 1, 2019 through the Embase and Medline databases using Boolean operators to locate appropriate articles.A total of 637 articles were discovered after the removal of duplicates, and 46 of these were selected for evaluation. Further, a quality assessment was performed using GRADE evaluation criteria.Shoulder finish line preparations had slightly better marginal fit compared to chamfer finish lines. Crowns obtained from digital impressions had comparable to superior marginal adaptation compared to conventional impressions. Increasing cement space showed to improve zirconia crown adaptation. Cementation and veneering zirconia frameworks found to increase the marginal and internal gaps. Limited information is available on the effect of the alteration of sintering time/Temperature and/or sintering techniques on the adaptation of zirconia crowns. Most of the selected studies had a moderate quality assessment evaluation. Future studies could investigate the chair‐side, ultra‐fast sintering effect on the marginal gap of zirconia crowns. The purpose of this study is to systematically review zirconia crowns and/or coping studies related to marginal and internal fit; further, this study is aimed to map all the factors that influenced the fit of zirconia crowns and/or copings.22.1The focused question was determined according to the well‐established PICO strategy 2009. (1) Population: crown or coping prostheses fabricated in vitro. (2) Intervention: zirconium oxide material. (3) Comparison: N/A. (4) Outcome: marginal and internal adaptation. The focused question of the presented review was “Within the available in‐vitro studies on full coverage crown or coping prostheses, what are the factors affecting the marginal and internal adaptation of zirconium oxide crowns and/or copings?”Dental Materials, Journal of Oral Rehabilitation, Journal of Prosthetic Dentistry, Journal of Prosthodontics, International Journal of Prosthodontics, International Journal of Periodontics and Restorative Dentistry, and Quintessence International. In addition, the references of the selected articles were reviewed for possible inclusion.The search strategy involved carrying out an electronic search through Embase and Medline using Boolean operators to locate appropriate articles as described in Table 2.2The search inclusion criteria were: studies published between December 1, 2009 and September 1, 2019 and limited to in vitro studies published in peer‐reviewed journals, articles written in English, which contained all or part of the key words in their headings or abstract, articles assessing the marginal and/or internal adaptation on single crowns for tooth‐supported restorations. The search was restricted by excluding “implant‐supported prostheses” and review articles.2.3The titles and abstracts of all articles were reviewed by two independent reviewers (W.A. and A.G.). Disagreement between the two reviewers was resolved by discussion. Upon identification of an abstract for possible inclusion, the full text of the article was reviewed and cross‐matched against the predefined inclusion criteria. Figure 2.4The following data were extracted from each article: type of fabrication system, factors tested that influenced the fit, sample size, type of finish line/preparation design, cement thickness, measurement method, number of measurements per sample, and marginal and internal gap measurements. Any variable that could not be extracted was scored as not reported (“nr”).2.5The interobserver calibration was evaluated by Cohen's Kappa and the chosen cut‐off point was 80%. GRADE criteria were used to provide a framework for quality assessment of the selected studies , use of different zirconia materials (13);Comparisons between digital and conventional impression techniques (6);Effect of cementation (7);Effects of different finish line configurations (4), depth or curvature (2), width (1), cement space (1), and changing the occlusal preparation (1);Effect of veneering (5), using different veneering techniques (1);Influence of using different die materials with or without powder (1);Altering sintering protocols (2).The factors that showed influence on the fit of zirconia crowns were the following: (N = number of papers)3.2Sectioning after cementation (10);Replica technique (12), Digitalized replica technique (1);Triple‐scan optical protocol (2);Micro‐computed tomography (micro‐CT) (1);3D coordinate measuring system (CNC Rapid) (1);Weight technique (1).Direct view technique was the method used in most (20) of the papers reviewed. The other methods were as follows: (N = number of papers)Assessing measuring points varied between studies even within each measuring technique, as shown in the summary table of included articles Table . The sam3.3Table 4The purpose of this systematic review is to map all the factors influencing the fit of zirconia crowns and/or copings and to update the latest review published in 2011 by Abduo et al. . A cliniSixty percent of the reviewed studies scored “moderate” according to GRADE evaluation criteria. Evaluators were moderately confident in the effect estimate owing to the high variability of methodologies, absence of many important details, and/or quality of the peer‐reviewed journal. Seventy four percent of the studies were found to be missing the sintering protocol details, including the time/Temperature (t/T) ratio, as well as the technique used for sintering. Thirty percent of the studies investigated the effects of using different manufacturing systems , Ceramill and Neoshape , or Lava and Neoshape , respectively. The fact that the fabrication of the copings took place in three different laboratories according to the system used limits the validity of extrapolating the results to reflect the clinical conditions. The accuracy of data acquisition varied according to the system used and several optical impression technologies. In addition, the software used and the milling accuracy differed. However, the majority of crowns manufactured by the various ceramic systems satisfied the requirements for marginal adaptation.Lins et al.  comparedMarginal and internal adaptations of zirconia were staggered and varied among the conventional and digital CAD/CAM ceramic systems. Multiple studies demonstrated superior . In contrast to most studies, the study found that the chamfer finish line yielded a better marginal adaptation compared with the shoulder finish line. Vojdani et al.  or the replica technique. Assessment of internal fit using microscopes is a destructive method that requires sectioning of the specimen. One of our selected studies evaluated the marginal and internal fits of zirconia crowns using micro‐CT; meanwhile two studies used the triple scan technique, one used CNC‐Rapid profilometry, and one used the weight technique. Therefore, direct comparisons between studies were not possible, as studies varied in their methods of measurements as well as other factors previously mentioned.According to the previous studies, there was no consensus on how many measurements should be taken per specimen to obtain an accurate and clinically relevant conclusion on marginal and internal gaps. In addition, our findings highlighted the importance of obtaining individual measurements without combining the results, which complicates interpretation of the results in terms of their clinical relevancy. Groten, Axmann, Probster, and Weber  suggesteNone of the studies evaluated the effect of aging on the marginal and internal adaptation of zirconia restoration. Few studies have attempted to evaluate the effects of sintering parameters on the mechanical properties of zirconia or to compare conventional sintering techniques  (first‐ and second‐generation zirconia), whereas few studies investigated the fit of the third‐generation zirconia 4 and 5 mol% yttria partially stabilized zirconia. Meanwhile, many studies failed to specify the type of zirconia material used in their study, and none of the reviewed studies investigated the fit of nano‐structured zirconia materials.Veneering porcelain on zirconia copings increased the marginal gap compared with that without veneering. Layering technique showed higher marginal gaps compared with press and CAD‐on techniques.Regardless of the type of cement use, cementation increased the marginal gap of zirconia crowns. Further studies should focus on the effect of cement thickness and load applied during cementation on the marginal adaptation of zirconia crowns.Within the limitation of this systematic review, we can conclude the following:Precise marginal fit is an essential component for the clinical success of dental restorations. Misfit of the prosthesis margin generates a potential space between the restored and prepared tooth; this gap can accumulate bacterial plaque and consequently jeopardize the longevity of the treatment. Therefore, understanding the factors influencing the marginal and internal adaptability of zirconia prostheses will assist in the improved preparation, designing, and processing zirconia prostheses for achieving clinical success.The authors have no conflicts of interest to declare.


The results revealed 18 discriminative genera in the microbiomes of the two cohorts out of which 16 genera were enriched in VC and the remaining two in PFR group. These discriminative genera were inferred to have antimicrobial, anti-inflammatory, and probiotic function. Only two pathogenic bacteria were differentially abundant in 20% of the PFR samples. PCoA and heatmap analysis showed that the vitreous microbiomes of VC and PFR formed two distinct clusters indicating dysbiosis in the vitreous bacterial microbiomes. Functional assignments and network analysis also revealed that the vitreous bacterial microbiomes in the control group exhibited more evenness in the bacterial diversity and several bacteria had antimicrobial function compared to the PFR group.Ocular microbiome research has gained momentum in the recent past and has provided new insights into health and disease conditions. However, studies on sight threatening intraocular inflammatory diseases have remained untouched. In the present study, we attempted to identify the bacterial microbiome associated with post fever retinitis using a metagenomic sequencing approach. For this purpose, bacterial ocular microbiomes were generated from vitreous samples collected from control individuals (VC,  Mycobacterium tuberculosis (Tuberculosis), Salmonella typhi (Typhoid), Leptospira spp. (Leptospirosis), Rickettsia spp. ), protozoa (Toxoplasma gondii (Toxoplasmosis)), and viruses [Several ocular manifestations like conjunctival congestion, uveitis, episcleritis, neuroretinitis, dacryoadenitis, and retinitis  have bee viruses ,5,6,7,8. viruses ,2. DespiStreptococcus gordonii, S. oralis, S. sanguinis, S. anginosus, Coxiella burnetii, and Bartonella quintana) [Routine culture and PCR based methods have failed to identify microorganisms associated with the vitreous of PFR individuals . This fauintana) .In the present study NGS was employed to understand the microbial composition in the vitreous of healthy controls and individuals with postfever retinitis. This approach would be helpful in identifying specific microorganisms present, if any, in the vitreous of patients and would also be useful for understanding the changes in the microbiome due to the prevailing inflammatory conditions. The present study would mainly focus on the alterations in bacterial microbiomes in the vitreous of individuals with postfever retinitis (PFR) compared to the vitreous of the control group (VC).n = 9) (n = 19) served as controls (VC) since these individuals had no PFR and no other ocular or systemic indication   followindication . Sample Vitreous fluid (200 µL) was used to extract DNA using PureLink DNA extraction kit . Quality of the DNA was judged by gel electrophoresis on a 1.0% agarose gel and the concentration was quantified using a Qubit 3.0 fluorometer . The extracted DNA was used for subsequent metagenome analysis. For this purpose, the total nucleic acids were amplified with random hexamers using amplification kit . The DNA was then processed for library preparation and sequenced according to the NEBNext Ultra DNA Library Prep Kit for Illumina Nextseq 500 PE sequencing protocol. Sequencing was performed on the Illumina Nextseq 500 platform using paired-end sequencing with 2 × 150 bp chemistry. In addition, at every stage of sample preparation, during DNA extraction, PCR reactions and whole genome amplification, sterile water was used as negative control to ascertain the possibility of bacterial contamination from the environment. However, PCR was consistently negative for amplification of DNA from water and the amplification mix without DNA which served as the negative control compared to samples. No sequences could be generated from the negative controls.The raw sequence reads from all the samples were analysed for identification of microorganisms. FASTQ files of the raw reads were analysed for quality parameters like read length, Phred score, GC content, and ambiguous bases. Subsequently, adapters were trimmed using trim-galore program . Post-trimming, reads were subjected to QC using FastQC (version 0.11.3). More than 90% of the data passed Q25 quality score, which was further used for downstream analysis. Sequences were then aligned with human reference genome (GRCh38) to remove human genome sequences and then the unaligned reads were recovered. Background sequences due to run processing were also filtered from the recovered unaligned reads. The unaligned reads were then assembled (denovo) using metaSPAdes genome assembler (Version 3.12.0) into contigs which were subsequently analysed using RAPSearch. RAPSearch is a tool for protein similarity search for short reads against nonredundant protein database from National Center for Biotechnology Information (NCBI). Meta Genome Analyser (MEGAN v 5.11.3) was used to identify the diversity for taxonomy assignment and KEGG pathway analysis.http://vegan.r-forge.r-project.org/) was used to rarefy the 28 bacterial microbiomes and to quantify alpha  and beta diversity indices. Genera showing a mean abundance >0.002% were used for the analysis. Wilcoxon signed rank test (with p < 0.05 as significant) was carried out to identify significantly different taxa in both VC and PFR group bacterial microbiomes at phylum and genus (discriminative genera) level. In addition, linear discriminant analysis effect size (LEfSe) was applied to identify discriminant bacterial genera. For this, the genera of VC and PFR groups were subjected to a nonparametric factorial Kruskal–Wallis (KW) sum-rank test p <0.05, LDA > 2.0 . Further, the statistical significance of the differences of the discriminative genera for VC and PFR group was tested by one-way ANOVA followed by t- test (p < 0.05). In the vitreous differentially abundant KEGG, functional pathways between VC and PFR were also ascertained using Wilcoxon signed rank test (with p < 0.05 as significant). Principal Coordinate analysis (PCoA) plot was generated for the 28 bacterial microbiomes using ade4 package in R (v 3.2.5). Jensen–Shannon divergence was used as a distance metric (http://enterotyping.embl.de/enterotypes.html). VC and PFR clusters on the PCoA plot were identified by subjecting the data to K-means clustering (k = 2) [The vegan package in R ( (k = 2) .CoNet , a Cytosn = 19) and Postfever retinitis  individuals   A,B. Furt samples A,B.Clostridium, Enterobacter, Acinetobacter, Klebsiella, and Lachnoclostridium). It was also observed that out of the 301 genera, 18 genera were differentially abundant in PFR individuals compared to VC (p < 0.05)  . In addi < 0.05) . A heatm < 0.05) A. Princi < 0.05) B. It is Anaerotruncus, Acetonema, Bacillus, Bdellovibrio, Geobacillus, Janthinobacterium, Mesorhizobium, Paenibacillus, Pelosinus, Sediminibacterium, Shigella, Sporomusa, and Thermosinus. The network analysis also showed that two genera, namely Arthrobacter and Shimwellia, were present only in the VC group and absent in the PFR group. Similarly, two bacterial genera viz., Pimelobacter and Tannerella were exclusively present in PFR group but absent in VC group . Five other genera viz., Acetonema, Anaerotruncus, Sediminibacterium, Sporomusa, and Thermosinus showed positive interaction with all the other genera  was done using the discriminative genera between VC and PFR groups separately A,B. In banalysed . In contr genera . RemainiKEGG pathway analysis of VC and PFR groups determined enrichment of functions related to infectious diseases, immune system, and signal transduction. Willcoxon signed rank test of the enriched KEGG pathways identified statistically significant pathways in PFR compared to VC group which included viz., ErbB signaling pathway, MAPK signalling pathway-fly, VEGF signaling pathway, PPAR signaling pathway, flavone and flavonol biosynthesis pathways, steroid degradation pathway, and intestinal immune network for IgA production . It was Ocular microbiome studies that uncover microbial communities of the eye have revealed that the eye hosts a unique assemblage of microbes ,16. For Studies on gut microbiome associated with systemic human Ulcerative Colitis, systemic sclerosis ,23, and Firmicutes and Bacteroidetes were the predominant phyla irrespective of the disease condition [Firmicutes and Actinobacteria were present as the predominant phyla [Firmicutes and Proteobacteria as the major phyla in both control and PFR groups  , four antimicrobial genera , two proinflammatory genera (Propionibacterium and Shigella) and one anti-inflammatory genus (Sporomusa) were decreased in PFR compared to VC. One proinflammatory genera (Tannerella) was also increased in PFR. Decrease in genera with antimicrobial and anti-inflammatory properties and increase in proinflammatory would support PFR. What could not be explained is the increase in anti-inflammatory genera. Earlier studies had indicated that the genus Tannerella is associated with pathogenicity [Propionibacterium, an opportunistic pathogen with proinflammatory activity [Propionibacterium was associated with intraocular inflammatory diseases like Uveitis and Endophthalmitis [Propionibacterium in VC group was not anticipated. However, it is worthwhile considering the possibility that instead of Propionibacterium negatively influencing the 13 genera it is equally possible to consider that all these 13 genera in VC were together suppressing the negative effects of Propionibacterium. This indeed may be the case since these genera also possibly interacted with each other. Thus, based on the network analysis it appears that the bacterial microbiome in control group with multifaceted interactions could substantially minimise the activity of the proinflammatory bacteria and thus would maintain the bacterial microbiome homeostasis. While in the PFR group Propionibacterium had less negative interactions with other genera compared to control group. This may suggest that the bacterial diversity in PFR group has less protective function against proinflammatory bacteria compared to control group.Previous cultivation-based assessments as well as metagenomic sequencing based analysis indicated that vitreous body of the eye is sterile and contains only a few microbial cells in individuals without eye infection . Therefo < 0.05) . Further < 0.05) C. Functi < 0.05) . When thgenicity ,35. The genicity . Microbeactivity ,38, exhihalmitis . TherefoKEGG pathway analysis showed enrichment of 14 pathways with functions related to metabolic pathways and signal transduction in VC and PFR group. Amino acids serve as the metabolic mediators for the cross talk between host and the microbiome and thus the amino acid metabolic pathways would differ at the site of infection compared to the healthy state . In PFR The major limitation of the study was recruiting healthy individuals as controls for the study. Therefore, vitreous fluid collected from individuals undergoing ophthalmic surgery for macular hole or rhegmatogenous detachment were used in the study. The other limiting factor is that PFR is a very rare ocular disease and therefore recruitment of patients is very time consuming and requires ethical compliance for vitreous biopsy.The study confirms the presence of bacteria in the vitreous fluid.(i)Demonstrates that the bacterial microbiomes of vitreous fluid from VC and PFR individuals could be discriminated at the genera level.(ii)The vitreous fluid of VC individuals showed increase in abundance of anti-inflammatory and antimicrobial genera and decrease in proinflammatory genera.(iii)The vitreous fluid of PFR individuals showed decrease in abundance of anti-inflammatory and increase in proinflammatory genera.(iv)KEGG pathway analysis identified significant increase in signalling pathways in PFR group that are associated with inflammatory cytokines.


Health related quality of life (HRQoL) and flourishing are constructs that encompasses a holistic representation of physical, psychological, and social health. The underlying psychological factors that can affect HRQoL and flourishing in sports participants is poorly understood. The purpose of this study was to i) evaluate HRQoL  and flourishing in recreational and elite and current and former cricketers; ii) determine the effect of resilience, playing-standard, and playing status on HRQoL and flourishing in cricketers.n = 2598 current and former cricketers, aged ≥18 years) collected cross-sectional questionnaire data including the Flourishing Scale, Short Form-8  and mental (MCS) component scores), resilience , highest standard-of-play, and playing status. Multivariable linear regressions with fractional polynomials were utilised, adjusted for age, gender, total cricket-seasons, comorbidity, ≥ 4-week time-loss injury, and orthopaedic surgery.The Cricket Health and Wellbeing Study ) 51.7(14.7) years, 61% played recreationally, 37% former cricketers) were included in analyses. The median (IQR) PCS was 51.4(46.9–55.9), MCS was 54.3(50.0–58.6), and Flourishing Scale score was 48 [ (1–7)] .Greater resilience was associated with better PCS (effect (95% CI) 1.41(0.70–2.11)), MCS (4.78(4.09–5.48)), and flourishing (2.07(2.55–3.59)) compared to less resilience. Playing standard was not associated with HRQoL. Playing at an elite standard was associated with greater flourishing ), compared with playing recreationally. Current cricket participation was associated with better PCS (3.61(2.92–4.30)) and flourishing scores (0.53(0.02–1.04)), compared to former cricket participation.Cricketers reported high levels of mental-components of HRQoL and flourishing, and this was similar in recreational, elite, current and former cricketers. Current cricket participation and a higher standard-of-play was associated with greater flourishing. Current cricket participation was also associated with better PCS, however playing-status was not related to MCS. Further research is needed to understand if cricket participation may have psychological benefits that persist beyond cricket retirement. Over 30% of adults globally do not meet physical activity recommendations . This isHealth-related quality of life is a multidimensional concept, incorporating multiple interrelated themes including physical function, social function, general health, energy, and mental health . The mosPeople can participate in sport at all standards-of-play, ranging from recreational  standards to elite sport participation , 36. HowFlourishing encompasses a holistic representation of physical, psychological, and social health , 44. TheThe purpose of this study was to i) evaluate HRQoL  and flourishing in recreational and elite, and current and former cricketers; ii) determine the effect of resilience, playing-standard, and playing status on HRQoL and flourishing in cricketers. It is hypothesized that greater resilience, having played cricket at an elite standard , and current cricket participation (compared to former cricket participation) will be associated with greater HRQoL and flourishing.A cross-sectional questionnaire was employed for the Cricket Health and Wellbeing Study. This study was approved by the NHS Health Research Authority (NRES), London Stanmore Research Ethics Committee (REC 15/LO/1274).The England and Wales Cricket Board national database was used in March 2017 to recruit current and former cricketers from all standards-of-play. A total of 28,152 current and former cricketers were invited by email to participate. Two thousand five hundred ninety-eight cricketers deemed themselves to be eligible, responded and consented to participate. Eligibility criteria for this study consisted of having played ≥1 cricket season, age ≥ 18 years old, no history of memory impairment, and completed study outcomes (the SF-8 (HRQoL) and The Flourishing Scale).In collaboration with the England and Wales Cricket Board, the questionnaire was created and was then piloted on a group of current and former cricketers. The questionnaire was designed to evaluate five aspects of health and wellbeing: i. cricket-related injury; ii. joint pain and osteoarthritis; iii. General health and disease prevalence; iv. physical activity; v. resilience, quality of life and flourishing (the focus of this study). Participant data was inputted into an encrypted database. RedCap® software  was usedHRQoL was captured through the Short Form 8 (SF-8) . The SF-Flourishing was assessed using The Flourishing Scale . The floPlease tell me to what extent you agree or disagree with this statement: When things go wrong in my life, it generally takes me a long time to get back to normal.’ This item question is part of a larger survey designed to investigate people’s comprehensive psychological wellbeing. This questionnaire was developed over two waves (2006 and 2012) of the European Social Survey. Over the two waves, based on the psychometric factor analysis, items were replaced for overall model best fit. Resilience was maintained for both waves. Response options were on a Likert scale of 1 (Agree strongly), 2 (Agree), 3 (Neither agree or disagree), 4 (Disagree) and 5 (Disagree strongly)  on most days of the last month?’ A history of cricket-related joint injury was assessed with the following question, ‘Have you ever had any cricket related injuries leading to more than 4 weeks of reduced participation in exercise, training or sport?’ Participants were stratified into never sustained a joint injury (0), and sustained a joint injury (1). Number of orthopaedic surgeries were assessed by asking the following question, ‘Have you ever had orthopaedic surgery ?’ Participants were stratified into never had an orthopaedic surgery (0), and had an orthopaedic surgery (1).Covariates were identified following discussion, literature review, and clinical reasoning. Covariates included age, gender, number of cricket seasons played, presence of a comorbidity, history of orthopaedic surgery, history of a cricket-related joint injury resulting in ≥4 weeks of reduced participation in sport, training or exercise. For the purpose of this study, comorbidities was defined as a history of diabetes, stroke, skin cancer, or other cancer, due to their potential effect on HRQoL and flourishing , 52, 53.Data was not assumed to be linear; thus, they were modelled with fractional polynomials. Multivariable linear regressions with fractional polynomials were performed to assess the effect of resilience, standard-of-play and playing status on HRQoL and flourishing. Unadjusted and adjusted coefficients and 95% confidence intervals (95% CI) were calculated. Due to only 3% of all participants were female, sensitivity analyses were performed. HRQoL and flourishing scores were split for male and females, and then Mann-Whitney U tests were performed to assess for HRQoL and flourishing differences. Further, regression analyses were performed, consisting of only males, to evaluate the effect of resilience, standard-of-play and playing status on HRQoL and flourishing. All assumptions for fractional polynomial regression were evaluated and satisfied . Resiliehttp://www.R-project.org/), using the dplyr package [Prior to analyses, all data were assessed for missingness. Due to the low percentage of missing data  complete case analyses were performed. All analyses were performed in R version 3.5.1 (R Core Team (2013). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. URL  package  for clea package , and the package .n = 91); played < 1 year of cricket (n = 2); < 18 years old (n = 7); reported history of memory impairment (n = 23); did not complete the SF-8 or The Flourishing Scale (n = 195)).A total of 318 participants from the Cricketers Health and Wellbeing Study were not eligible to take part in this study  met the eligibility criteria and were included in the analyses  points greater PCS, 4.78 (95% CI 4.09 to 5.48) points greater MCS, and 3.07 (95% CI 2.55 to 3.59) points greater flourishing scores, compared to cricketers that were not resilient ) (Table Current cricket participation was associated with 3.61 (95% CI 2.92 to 4.30) points greater PCS and 0.53 (95% CI 0.02 to 1.04) points greater flourishing scores, compared with former cricket participation. Playing status was not related to MCS scores (Table p = 0.423), MCS , or flourishing scores . There were similar relationships between resilience, playing-standard, and playing status on HRQoL and flourishing in male cricketers as compared to all cricketers  years, median BMI 27.3 (IQR 24.6 to 29.9), and median cricket seasons played were 30 (IQR 19 to 41) seasons. The female cricket mean age was 43.8 (SD 13.9) years, median BMI 24.4 (IQR 21.4 to 27.4), and median cricket seasons played were 9 (IQR 4 to 14) seasons. The male median PCS score was 51.4 (IQR 46.7 to 55.9), the MCS score was 54.3 (IQR 50.0 to 58.6), and the median flourishing score was 48 (IQR 45 to 52). The female median PCS score was 51.0 (IQR 46.0 to 58.3), the MCS score was 52.4 (IQR 46.6 to 58.3), and the median flourishing score was 48 (IQR 44 to 52). There were no statistical differences between male and female PCS  and better flourishing scores in current cricketers compared with former cricketers.As described within the methods, the HRQoL normative scoring is calculated using a sample of the 1998 United States general population. This sample was composed of cricketers from the United Kingdom. While both countries speak English, and share similar cultures, there are cultural and time differences. Due to this, the potentiality for cultural measurement invariance exists when scoring and interpreting this data , 59. MeaElite, recreational, current, and former cricketers reported similar physical-components of HRQoL compared to the general population. These findings are in contrast to a recent systematic review, in which former athletes reported impaired physical-components of HRQoL compared to the general population . HoweverIn contrast, all cricketer subgroups reported clinically meaningful greater mental-components of HRQoL compared to the general population. This supports previous research in which athletes reported improved mental-components of HRQoL in comparison to the general population , 67. ,FuAll cricketer subgroups reported high flourishing scores, demonstrating that participants viewed themselves in positive terms in important areas of functioning . While tCricketers that were resilient reported greater physical and mental-components of HRQoL and flourishing compared to cricketers that were not resilient. The association between greater resilience and better PCS scores was greater than the minimum detectable difference of two points , and theOne possible explanation for these findings, is that resilient cricketers with persistent joint pain  may be more likely to continue to perform physical tasks, compared to non-resilient cricketers (corresponding to greater HRQoL scores). This is supported by a randomised control trial, that found resilient patients with knee osteoarthritis, reported greater physical functioning compared to non-resilient patients with knee osteoarthritis . ImpaireAlthough playing standard was not related to HRQoL, having played elite cricket was associated with an estimated one point greater flourishing score compared to having played recreationally. While there are no studies investigating minimum detectable or clinically important differences in the Flourishing Scale, a difference of one point may not be clinically meaningful. This was the first study to evaluate the relationship between different standards of sports participation, HRQoL and flourishing. Our results suggest that sport participants from higher and lower standards have similar HRQoL and flourishing. Long-term stressors and environment have been shown to build resilience in athletes , 70, 78.Current cricket participation was associated with greater physical-components of HRQoL compared with former cricket participation , and this is likely to be clinically meaningful . CurrentIn order to expand on these findings, further research is required. Cricketers were found to exhibit increased mental-components of HRQoL and flourishing, and these relationships were present in both recreational and elite cricketers. Further, these relationships were maintained after ceasing to play cricket. Cricket is a potential physical activity intervention, that can be played at all ages and standards of play. Due to these findings, research is required to understand the efficacy of cricket as a physical activity intervention. Specifically, the contribution of cricket to mental-components of HRQoL, flourishing, and psychological strengths requires further investigation. Other potential research avenues include investigating if resilience is inherent or learned during cricketer participation, the role of other sports and physical activities in relation to resilience, and how cricket and other sport participation can affect HRQoL and flourishing.This study provided detailed analyses of physical and mental-components of HRQoL, in cricketers from all standards and abilities. Resilience was captured through a single-item question derived from the European Social Survey. While this question was developed over two waves of the European Social Survey, this single-item measure has not been validated or assessed for reliability beyond this survey. Using a validated and reliable patient reported resilience outcome measure would allow for improved inferences. The cultural measurement invariance for the SF-8, and its iterations has not been investigated. This decreases the precision of the HRQoL scoring and interpretation. In this sample, cricketers could play other sports, and perform other physical activities, which could affect HRQoL, flourishing, and resilience. Although the authors controlled for gender, number of cricket seasons played, history of ≥ 4-week time loss joint injury, and history of orthopaedic surgery in the multivariable analyses, playing other sports may still have a confounding effect upon the results. Due to the study recruitment methodology, it is not possible to determine a true response rate, decreasing the capability of this study to understand selection bias. Only 3% of all participants were female. This decreases the generalisability of these findings to female cricketers. Due to this, sensitivity analyses were performed. There were no differences in HRQoL or flourishing between males and females, and the only male analyses resulted in similar findings compared to the full analyses. However, future research is still required to evaluate a larger sample of female cricketers. This study only used self-reported outcome measures, which may cause common method bias. Finally, participants were asked to recall events that may have occurred in the past, which could create recall bias.Mental-components of HRQoL  were better than the population average, in elite, recreational, current and former cricketers. Despite former cricketers reporting worse physical components of HRQoL  compared with current cricketers, mental components of HRQoL were comparably high in former and current cricketers. All cricketers reported high flourishing scores, although elite cricketers reported greater flourishing than recreational cricketers, this may not be clinically meaningful. Greater resilience was associated with better mental and physical components of HRQoL, and greater flourishing scores, in all cricketers. Further research is needed to understand if cricket participation at all playing standards, may be associated with positive mental impacts that persist beyond cricket participation. Additional research is required to determine whether these results are comparable in a larger sample of female cricket players, and if psychological benefits of sports participation can assist in reducing the personal burden of joint pain and osteoarthritis, which are common following prolonged sports participation.


Joint mechanical impedance, which describes the instantaneous relationship between kinematic perturbations and the resulting torque response, plays an important role in the way humans ambulate, interact with the environment, and respond to disturbances. Recent studies have quantified how the stiffness component of mechanical impedance varies during walking. However, the extent to which humans can voluntarily regulate leg joint stiffness is not yet known. Our study sought to quantify the accuracy and precision of the neuromotor system to voluntarily regulate ankle joint stiffness while seated, and compare these data to the well-known abilities to regulate ankle joint torque and position. We tested individuals’ ability to to regulate these quantities at three different magnitudes: 20%, 40%, and 60% of a maximum value. Our results showed that subjects were able to voluntarily regulate ankle joint stiffness, and that the normalized accuracy and precision of stiffness regulation were not different than those of position or torque for targets at magnitudes of 20% of a maximum value. However, the accuracy and precision of stiffness regulation were statistically different than those of position and torque for targets at magnitudes of 40% of the maximum values. At moderate targets, the similarity of the ability to regulate ankle joint stiffness when compared to the abilities to regulate joint torque and position highlights the importance of a comprehensive description of lower-limb biomechanics that includes consideration of joint mechanical impedance, in addition to the common descriptions of joint torque and position. These data have formed the core of locomotor biomechanics for over a century. In addition, this information has many important implications, including serving as a benchmark for diagnosis and treatment of neuromotor pathologies and providing a guide for the development of assistive technologies, among other uses. However, this fundamental biomechanical description of human locomotion is incomplete.Our fundamental understanding of how human locomotion is regulated by the neuromuscular system mainly stems from analyses of how the legs are moved during gait (joint angles), and how effort is provided throughout locomotion (joint torques)2 increases the mechanical stiffness of a joint, without necessarily affecting the angle or net torque4. Joint stiffness, along with inertial and viscous properties, comprise a representation of mechanical impedance, components of which that can be varied throughout movement7. Joint mechanical impedance regulates the instantaneous torque response that accompanies changes in joint position, governs the body’s response to unexpected disturbances, and regulates how energy is stored, exchanged, and dissipated by the joints of the leg8—concepts critical to human locomotion9. Thus, mechanical impedance is a fundamental biomechanical property that varies continuously and subconsciously during gait, alongside joint angles and torques.The human neuromuscular system permits regulation of joint stiffness properties independent of joint torque and angle. When contracted, muscles only provide force in tension—they cannot provide forces in compression. Consequently, bidirectional joint torques are achieved using agonist-antagonist muscle groups. The simultaneous co-activation of agonist-antagonist muscles (among other mechanisms)10, and is estimated using system identification analyses. During static tasks, the influence of many factors on joint impedance has been characterized21. Historically, these properties have been difficult to measure during dynamic tasks, such as locomotion. However, recently, several groups have pioneered the tools to quantify how ankle impedance varies during locomotion. Rouse et al. showed that the stiffness component of ankle impedance increases throughout the stance phase of walking23, and Shorter and Rouse demonstrated that ankle stiffness decreases during the terminal stance phase24; Lee and Hogan showed that stiffness remains low during swing phase of gait, increasing slightly before the onset of the subsequent stance phase25. Combined, the results of these studies have provided a more comprehensive understanding of gait biomechanics, complementing the traditional biomechanical gait representations of joint angle and torque variation.Much is known about leg joint mechanical impedance during static, postural tasks. Mathematically, impedance is typically represented as a second order system et al. and others showed that humans can achieve an ankle joint position accuracy of approximately 2 degrees, approximately 3% of the population average range of motion, with a standard deviation (i.e. precision) of 1 degree29; the high accuracy and precision of ankle position regulation highlights its importance in neuromotor control. In addition, researchers have quantified humans’ ability to regulate ankle torque, and have shown that people are able to reproduce both plantar flexion and dorsiflexion torques within an average of 1.7 N·m ± 1.2 N·m, approximately 5% of the population average maximum voluntary contraction in either direction29. Although this previous work has provided much insight into the capacity of the neuromotor to closely regulate ankle joint position and torque, it cannot be used to infer information about regulation of ankle stiffness. Researchers have recently investigated how humans perceive changes in joint stiffness. Azocar and Rouse have determined that humans are able to detect a 12% and 13% change in stiffness, when interacting with a virtual mechanical impedance at the ankle and knee, respectively30. Elucidating sensorimotor perception is one important step towards fully characterizing the proprioception and neuromotor regulation of joint impedance, but the accuracy and precision of the individual’s ability to voluntarily regulate joint stiffness remains unknown.Mechanical impedance has provided new insight into locomotor biomechanics, but little is known about how the nervous system regulates these quantities. Discovering how humans can voluntarily regulate their joint mechanical impedance is an important step in expanding our modern understanding of human locomotor control. Researchers have previously studied the accuracy and precision of the control of ankle joint position and torque, elucidating key properties that describe the human ability to regulate biomechanics. Deshpande 24. We focused on the ankle joint because of its importance to locomotion, adding the majority of mechanical energy used to propel the body forward1. The intent of this work is to provide insight into how individuals voluntarily regulate ankle joint stiffness, and to quantify previously-unknown fundamental information about human neuromotor control. We hypothesized that there would be significant differences in the accuracy and precision of an individual’s ability to match a specified target stiffness . We additionally hypothesized that there would be a difference in accuracy and precision of target matching when comparing ankle stiffness matching to ankle torque and position matching tasks. Our results demonstrated that the accuracy and precision of ankle stiffness control was not statistically different than the accuracy and precision of ankle torque or position control in matching tasks. Specifically, we found that performance across the three domains  was most similar at moderate intensity levels, with stiffness matching error increasing with higher muscle activation.The objective of this study was to quantify the accuracy and precision of the human ability to regulate ankle joint stiffness, and to compare these data to the more commonly-studied regulation of joint torque and position. We chose to study the stiffness component of mechanical impedance because it changes significantly during gait, and accounts for the vast majority of the torque responsekmax) determined in a pilot study. For each stiffness target, 14 subjects were permitted 12 sequential attempts to match the target value, with accuracy feedback provided at the end of each attempt. Analyses were performed on the final 10 trials of each task to mitigate the effect of discovering target location in the first two trials. Our results show that, following a short training protocol, subjects were able to modulate stiffness via voluntary isometric co-contraction of the muscles about the ankle. Mean absolute error ranged from approximately 6.1 N·m/rad to 11.3 N·m/rad, with a precision of approximately 2.8 N·m/rad to 8.5 N·m/rad. Averaging across all subjects and all target levels, the average error in stiffness target matching was 9.2 6.3 N·m/rad (mean s.d.). To compare target matching accuracy (mean of error) and precision (standard deviation of error) across target magnitudes, a statistical analysis of variance (ANOVA) was performed. Accuracy varied significantly between target magnitudes  and subjectsIn this study, subjects attempted to match their ankle joint stiffness to a desired target value. To modulate joint stiffness, subjects co-contracted agonist-antagonist muscles of the ankle, while maintaining minimal net torque. The target values were 20%, 40%, and 60% of a maximum stiffness value . Similarly, precision differed significantly between target magnitudes  and subjects   and the mean precision of the 20% target was significantly different than the mean precision of the 40% target (p = 0.01). and maximum reachable plantar flexion torque (Tmax), respectively. Analogous to the stiffness matching tasks, accuracy feedback was provided following each trial, and analyses were performed on the last 10 trials.We conducted an analogous experiment of matching joint position or torque to provide a comparison between regulation of joint stiffness, each described as a different F2,83 = 0.82; p = 0.45), nor was there a significant difference between subjects . However, accuracy did vary significantly between target magnitudes , and there was a significant interaction between domain and target magnitude . Differences in precision with respect to domain approached, but did not achieve, significance . Precision also did not differ significantly between subjects . However, differences in precision between target magnitudes were significant and the interaction between domain and target magnitude also approached significance .The inter-subject average percent error for all tasks was used to compare accuracy and precision between position, torque, and stiffness target matching abilities Fig. . An ANOVF1,27 = 0.34, p = 0.57; position: F1,27 = 2.17, p = 0.16). Finally, to facilitate direct comparison, statistical tests across domains were performed for targets that were achieved in all tests (20% and 40% of the domains’ maximum levels).Three targets were collected for each domain; however, the torque and position domain included one target in the dorsiflexion and two targets in plantar flexion direction. These targets were chosen because both positive and negative values have meaning in the position and torque domains. Stiffness, however, is only physically meaningful for positive values–the analogy between the domains does not hold for this concept. For position and torque, data were collected for one dorsiflexion target at the 20% of maximum level, and these data were compared to the 20% plantar flexion target. There was no statistical difference between plantar flexion and dorsiflexion, thus analyses focused on the plantar flexion direction only  was used to estimate model fit. VAF quantified what percentage of the variance of the measured torque data was explained by the estimated torque data, where estimated torque was obtained via the mechanical impedance model. High VAF values were obtained for all stiffness trials (mean VAF = 97.3 ± 2.4), demonstrating that the mechanical impedance model fit the data well.24. The stiffness component of mechanical impedance is an important property for locomotion, since it governs the body’s response to irregularities in terrain, as well as how mechanical energy is stored and transferred between the joints of the legs. However, despite the recent quantification of these properties during gait, a gap remains in our understanding of how the neuromotor system regulates leg joint impedance. The intent of this study was to provide insight into the human ability to voluntarily regulate ankle joint stiffness, specifically in terms of accuracy and precision. Co-activation of antagonist muscles has previously been shown to enable voluntarily modulation of joint stiffness during static postural conditions4, but, to the best of our knowledge, this strategy had not been quantitatively measured in healthy subjects, or examined in the context of the larger framework of motor control. Consequently, in this study we compared the ability to regulate ankle joint stiffness to the well-known and intuitive abilities to control joint position and torque. These data lay the foundation for understanding the importance and limitations of the neuromotor system’s ability to voluntarily regulate leg joint dynamics.Until recently, the mechanics of locomotion were described mainly by the regulation of joint position and torque; however, new studies have quantified the underlying mechanical impedance of the ankle, which also varies during gait24. However, the high stiffness during locomotion is likely the result of approaching the ankle joint’s range of motion limits, and thus is not due to muscle activation alone, and is compounded by the parallel stiffness of the physiological mechanical structures19. Future work is needed to ascertain how joint stiffness regulation is affected by covariation of net torque and joint angle outside of the neutral configuration.Subjects were able to voluntarily regulate ankle joint stiffness to match targets that spanned achievable joint stiffness magnitudes. Target matching accuracy and precision decreased with increasing target magnitude. The stiffness magnitudes chosen in this study were based on the maximum achievable ankle stiffness obtainable during isometric co-contraction, with near-zero net torque. However, ankle stiffness in this configuration is substantially less than what is observed at different ankle torques and joint angles, such as what has been shown during locomotion. For example, during gait, ankle stiffness is as high as approximately 420·N m/rad for a 70 kg individual, almost ten times greater than what was tested in this studyet al.29. The near constant error may be the result of the limits of physiological sensing mechanisms, such as Golgi Tendon Organs that sense muscle force, or muscle spindles and mechanoreceptors that assist in the sensation of joint angle31. In contrast, both the accuracy and precision of stiffness error  increased with increasing target magnitude. The opposing trends may result from the unfamiliar nature of stiffness regulation, when compared to the intuitive concepts of angle and torque regulation. All subjects were given time to become familiar with the task of co-contraction to increase joint stiffness and were able to achieve the targets. However, longer training periods may improve stiffness accuracy within the limited number of trials assessed in this work. Alternatively, the reduction in stiffness domain accuracy and precision may result from the lack of direct physiological sensation of stiffness, which instead must be indirectly sensed via fusion of joint torque and position sensations. It is also important to note that while both results are reported and discussed here, the accuracy results cannot be generalized to longer analysis windows, as accuracy effectively loses meaning as the number of trials tends towards infinity. Further studies are needed to determine how target-matching accuracy and precision may change with greater training and skill.Accuracy and precision compared across domains were not significantly different at the lower target magnitude, but differed significantly at higher magnitude. For the target at 20% of the domain’s maximum, accuracy and precision were comparable across all domains . It is likely that the ability to control stiffness, position and torque may depend on the configuration of the limb. Future experiments are needed to ascertain how stiffness can be regulated in dynamic tasks and at varying operating conditions.Our goal was to quantify the neuromotor ability to voluntarily regulate joint stiffness. As voluntary regulation of joint stiffness via muscular co-contraction is a novel task for most people, learning to co-activate muscles may have affected the results. We attempted to minimize the influence of motor learning on our results through several measures. First, the order of domains was randomized, as was the order of targets within a domain, for each subject. This randomization served to minimize the effects of any confounding factors that may co-vary with task order. Additionally, all subjects performed practice co-contraction trials preceding the stiffness protocol. These were included to confirm all subjects were proficient in maintaining equal co-contraction throughout perturbation trials, which was necessary to assure our measurements were representative of physiological stiffness. Subjects completed practice trials until they could complete three consecutive trials with net torque sufficiently close to zero, as indicated by the trials each having a Variance Accounted For (VAF) above 90%, which confirmed our mechanical impedance estimation model fit the data well. Trials with VAFs above 90% had low variability in estimated stiffness and were consistently achievable by subjects. Finally, only the last 10 of the 12 trials were included in our data analysis to eliminate the period at the beginning of each trial in which subjects were attempting to locate the target.48. Voluntary prediction and phase locking, which dominate reflex dynamics, were minimized by selecting stochastic low-frequency perturbations3. Despite these measures, it is possible that intrinsic reflex responses contributed to the measured stiffness values.Joint stiffness is known to depend on multiple factors, and while our objective was to isolate voluntary changes in joint stiffness, these other factors may have influenced our results. Stretch reflexes, passive tissue properties, and muscle activation all contribute to physiological joint stiffness, and our experiment was designed to mitigate the effects of reflexes and passive tissue properties. The stiffness from passive tissue properties was measured and subtracted from the estimated stiffness values. Reflex contributions can be minimized by carefully selecting the parameters of the mechanical perturbations applied to the ankle during stiffness measurements. Changes to joint position elicits monosynaptic reflex responses, which can impact joint dynamicsThe maximum values used to scale target locations were inconsistent across domains. Torque and position targets were scaled based on subject-specific ranges; however, a single value for maximum stiffness was used for all subjects, which was determined via a pilot study. Our decision to use a single value for maximum stiffness stemmed from the difficultly and highly fatiguing nature of determining subjects’ maximum voluntary stiffness. Furthermore, some subjects required many more trials to obtain usable maximum stiffness values, which created inconsistency in the training protocol. Using a constant value for maximum stiffness across subjects may have increased the variability in the accuracy and precision but would not have affected the mean values obtained.Fourteen able-bodied subjects  aged between 20 and 51 years  were recruited to participate in the study. Subjects had no prior history of neurological disease or injury to the ankle, and informed consent was obtained prior to beginning the experiment. The protocol was approved by the Institutional Review Board of Northwestern University (IRB protocol STU00202024), and all research was performed in accordance with relevant guidelines and regulations.Subjects were seated in an adjustable chair  coupled to the Neurobionics Rotary Dynamometer a custom frame-mounted motor  with a six-axis load cell   and the pseudoinverse auto-correlation matrix (φxx). This impedance impulse response function was subsequently integrated over time to yield an estimate of joint stiffness, the static component of the mechanical impedance transfer function. Stiffness was calculated from the middle eight seconds of the analysis window, with one second at the beginning and end of each trial removed to eliminate any artifacts arising from starting and stopping the trial. The stiffness value calculated from each trial was then used for analysis and display, and the protocol was repeated for each of the three stiffness targets.To measure accuracy and precision of joint stiffness regulation, subjects attempted to match their ankle stiffness to a target value via isometric co-contraction of the muscles of the ankle. Stiffness was measured by applying system identification techniques to torque and position data collected by the dynamometer. During each trial, Gaussian white noise perturbations with a mean amplitude of 2° were filtered using a 4th order Butterworth filter with a cutoff frequency of 5 Hz, and applied using the dynamometer. Prior to the experiment, three estimates of resting ankle joint stiffness were obtained where the subject did not co-contract. These data were used to measure the stiffness generated purely by passive musculotendon properties. Targets were subsequently calculated to be 20%, 40%, and 60% between the subject’s passive stiffness and a maximum stiffness value obtained in a pilot study prior to the experiment. This maximum stiffness value was calculated from the pilot study in which nine able-bodied subjects  were instructed to exert a maximum co-contraction of the muscles about their ankle during 10-second duration perturbation trials. The maximum stiffness for our experiment was chosen to be 85·N m/rad, which was the highest stiffness reachable by all subjects in the pilot study. The mean maximum stiffness across all subjects in the pilot study was 92.3·N m/rad with a standard deviation of 26.6·N m/rad. Full data from the pilot study is available in Supplementary Table For a comparison with the neuromotor ability to voluntarily regulate joint torque, we quantified accuracy and precision of ankle torque regulation. Accuracy and precision of ankle joint torque were directly measured by the dynamometer. Isometric maximum voluntary contractions (MVCs) were collected prior to the target-matching protocol in both the plantar flexion and dorsiflexion directions. Targets were calculated to be 20% of the subject’s plantar flexion MVC, 40% plantar flexion MVC, and 20% dorsiflexion MVC. Similarly to the stiffness protocol, the number of targets was chosen to prevent fatigue, while adequately spanning the range of joint torques. In each trial, the dynamometer held a fixed position of 0° while the subject attempted to match the torque target. Torque data were recorded throughout the trial, and the middle three seconds were used for analysis and display. One second at the beginning and end of each trial were removed to eliminate any effect of the subject starting and stopping the trial. The average change in torque during the analysis window was 4.6·N m/rad. The protocol was repeated for each of the three torque targets.i.e. θ = 0) for use in calculating percent error. Initially, the subject’s range of motion was quantified. Targets were chosen to be 20% of the maximum plantar flexion angle, 40% of the maximum plantar flexion angle, and 20% of the maximum dorsiflexion angle. In each trial, the subjects interacted with the dynamometer with admittance control, which rendered the dynamics of a virtual spring-damper system and allowed the subject to freely move his or her ankle. The stiffness component of the virtual spring mass damper was selected to be 0.1·N m/rad, the damping component 20·N m s/rad, and the inertia 1 kg·m2. The mechanics of the spring-mass-damper were chosen so that there would be no restoring torque acting on the subject during the analysis window. The average interaction torque during this period was 0.005·N m. Subjects were encouraged to explore the range of motion before proceeding to the target-matching tasks. Following each trial, the footplate was reset to the starting position to maintain consistency between trials. Similarly to the torque protocol, subjects had five seconds to maintain the position target, and the middle three seconds were used for analysis. The average change in position throughout the analysis window was 0.03°. Following the completion of each trial the mean value was displayed on the plot. As with stiffness and torque tasks, the protocol was repeated for each of the three position targets.For a comparison with the neuromotor ability to control joint position, we quantified accuracy and precision of ankle position regulation. In this task, subjects attempted to match their ankle joint position to various target positions, measured as excursions from the initial configuration detailed above. All positions reported herein are relative to this initial configuration. We measured the ability to match excursion angle, rather than an absolute position, to avoid inconsistencies that arise when defining a reference equilibrium angle  of 0.8. We chose to detect a change of 10% because it was approximately the average difference in target matching error between stiffness targets in our pilot study.Our goal was to compare the accuracy and precision of joint stiffness regulation to that of joint position and joint torque regulation. This was accomplished by comparing the inter-subject average percent error for all tasks. Percent error was chosen to normalize and compare accuracy and precision across different domains, which eliminated comparisons with different units. Statistical testing consisted of an analysis of variance (ANOVA) with target level 20%, 40%) and domain  treated as fixed factors, and subject treated as a random factor. Our model also included the interaction between domain and target magnitude. Post-hoc comparisons were performed using Bonferroni corrections, and the significance level of all tasks was set 0% and doSupplementary tables.


Split thickness skin graft is a widely accepted technique to cover large defects. Shearing, hematoma and infection have often been attributed as major causes for graft loss. Autologous platelet rich plasma (PRP) has been used in various treatment modalities in the field of plastic surgery for its healing, adhesive and hemostatic properties owing to the growth factors that are released. This Study primarily throws light on the usage of PRP over difficult Burn wound beds to augment graft uptake and attenuate complications.The patients were divided into two groups of those who were subjected to use of autologous PRP as a preparative burn surfacing and the control group who underwent standard method of treatment.Patients in PRP group significantly showed a higher graft adherence rate as compared to those with other method. It also reduced pain, and hematoma formation.Application of PRP is a safe, cost effective, easy method to increase graft adherence rate in patients with burns where graft loss is noticed and there is shortage of donor sites. Shearing, hematoma and infection have often been attributed as major causes for graft loss. Autologous platelet rich plasma (PRP) has been used in various treatment modalities,9,10 PRP functions as a fibrin tissue adhesive with hemostatic and tissue sealing properties, but it differs from fibrin glue and other platelet-poor tissue adhesives because its platelets provide a unique ability to promote wound healing.11 PRP provides an immediate surgical hemostatic agent that is biocompatible, safe, and effective. It accelerates endothelial, epithelial, and epidermal regeneration, stimulates angiogenesis, enhances collagen synthesis, promotes soft tissue healing, decreases dermal scarring, enhances the hemostatic response to injury, and the high leukocyte concentration of PRP has an added antimicrobial effect.12 The application of autologous PRP to STSG sites has been recently described for immediate skin graft anchorage as well as inosculation of the STSG with nutrient-rich blood media.13,14 This Study primarily throws light on the usage of PRP over difficult burn wound beds to augment graft uptake and attenuate complications. Platelet-rich plasma (PRP) is an autologous product that concentrates a large number of platelets in a small volume of plasma.The study was performed in Department of Plastic, Reconstructive and Burns Surgery, SMS Hospital, Jaipur, India between 2017 and 2019. Totally, 200 patients were enrolled with written and informed consent and were divided into two groups of 100 each as case and control on a randomized basis. The patients were initially admitted and were resuscitated. They underwent dressings until the bed was ready for grafting. The patients in the cases group were subjected to use of PRP just before application of skin grafts. The patients in the control group underwent grafting by the standard method.13 patients venous sample was taken, collected in 10 mL ACD vials, and spinned for 10 min at 3500 rpm. PRP was applied on the wound bed as a thin film just before applying the graft and 5 mL for 100 square cm was used. Additional sutures were taken to fix as necessary. Non adhesive paraffin gauze dressing was applied over the grafted area. Dressing was conducted on day 2nd and subsequently on alternate days. Graft adherence was investigated on day 2nd and day 6th. Any hematoma formation and the cost were evaluated.The inclusion criteria were all patients with burns and healing ulcers and a serum albumin above 2.5 g/dL. The exclusion criteria were an active infection, age >70 years, presence of pus and discharge, immune-compromised patients, exposed ligaments/bone/cartilage, underlying comorbidities, uncooperative patients and drug abuse. To prepare PRP based on various reported methods,nd was 89 and 76 on day 6th for case and control groups, respectively. These figures on day 2nd and 6th in case and control groups were 85 and 70, respectively. All 100 patients who received the intervention (88.86±34.5) demonstrated significantly better graft uptake rate on day 2nd [t(51)=2.1 p=0.04], when compared to the 100 patients in the control group (425±31). There were 59 and 48 cases and controls for males, respectively and these figures for females were 41 and 52, respectively. The mean age of patients was 45.1 years in case and 48.2 years in control group. Graft adherence on day 2p=0.097], even women (55±8) attained higher score than men (53±7.8). The overall cost of PRP was only 200-300 Rupees, while staples and sutures’ cost was 2000-3000 Rupees. Two patients in the case group showed hematoma formation; while in the control group, hematoma formation was noticed in 8 patients. About 50% graft loss was observed in the case group (both of them were in the region of neck and axilla), while in the control group, 6 patients developed signs of local infection with 70%, 40%, 50%, 50%, 50%, and 70% graft loss. Donor site healing was uneventful and had a good aesthetic outcome in both the groups.There was no significant difference for sex, [t(8)=1.7, 12,15 It helps early vascularization by delivering these growth factors and increasing collagen synthesis. There are other benefits like reduced hematoma, infection, and cost. It has three stages of anchorage, inosculation and maturation, while the success of the first two stages is critical to the overall success of serum imbibition; revascularization ; and maturation. PRP is a biological product defined as a portion of the plasma fraction of autologous blood with a platelet concentration above the baseline. It is obtained from the blood of patients and collected before centrifugation.16 Normally, the platelet concentration is described as low: 0.5x, intermediate: 0.5-3, and high: 3-5 million/µl.In STSGs, keratinocytes on the basal layer show high proliferation rates, which may ultimately stimulate growth factor excretion. Chronic wounds may lack growth factors due to decreased production and release, trapping, excess degradation, or a combination of these mechanisms; thus delaying wound healing, which is overcome by PRP. While fibrin is crucial for early cell migration in the wound bed, collagen deposition allows wound maturation.et al.’s study done on forty post burn patients, PRP was safe and effective for fixation of skin grafts due to its adhesive nature and outcomes were better than securing skin graft to wound margins or bed with sutures, staples or glue.17 Schade and Roukis found that addition of PRP to split-thickness skin graft recipient sites enhanced primary healing and reduced healing time, likely as a result of shearing force reduction and enhancement of the wound environment with growth factors.18 A study by Kakudo et al. revealed that PRP promoted epithelialization and angiogenesis of split-thickness skin graft donor sites.19 In a recent study, Wanden-Berghe et al. found clinically a clear improvement in chronic wounds with an accelerated healing on application of PRP activated by calcium chloride.20 Application of PRP was shown to be safe, cost effective, easy to increase graft adherence in patients with burns, where graft losses are often seen and where there is a shortage of donor sites.We have been able to achieve high concentration of platelets by our technique of preparation. Use of PRP has been studied by many researchers. According to Gibran The authors declare no conflict of interest.


Although, free fascia lata autografts can be used to reconstruct various anatomical structures, little information is available about the status of such autografts several years after the procedure, especially in a clinical setting. Here, we describe our experience with a patient who underwent relaparotomy two years after incisional hernia repair using a fascia lata graft. A 79-year-old man underwent open hepatectomy for hepatocellular carcinoma. One year later, abdominal computed tomography revealed a locally recurrent tumor 1.5 cm in diameter and a giant incisional hernia measuring approximately 15 × 6 cm on the supraumbilical midline. After repeat hepatectomy, the incisional hernia was repaired using a free fascia lata patch as an interpositional graft. Two years later, the patient was readmitted because of recurrent tumors in the liver, and repeat hepatectomy was performed. During surgery, the fascia lata graft had survived well and become incorporated into the native fascia. We incised this fascia lata graft in the same way as for a normal laparotomy. After hepatectomy, the fascia lata graft was closed in layers with interrupted sutures. The patient was discharged on postoperative day 11 with no wound-related morbidity. Reconstruction of the abdominal wall and incisional hernia repair have been performed using an autologous tissue graft as an alternative to prosthetic materials, especially in patients with a risk of surgical site infection –3. A freHere, we describe our experience with a patient who underwent relaparotomy two years after incisional hernia repair using a fascia lata graft. To our knowledge, no previous reports have described details of relaparotomy in patients with autologous tissue grafts.A 79-year-old man underwent open hepatectomy for a hepatocellular carcinoma 4.3 cm in diameter. One year later, abdominal computed tomography revealed a locally recurrent tumor 1.5 cm in diameter and a giant incisional hernia measuring approximately 15 × 6 cm on the supraumbilical midline. Consequently, the incisional hernia was repaired using a free fascia lata graft patch after repeat hepatectomy. During the surgery, the fascia lata was harvested from the left thigh. An incision approximately 12 cm long was made on the lateral side of the thigh to allow for the dissection of subcutaneous tissue and harvest a piece of fascia lata measuring 16 × 8 cm. After the hepatectomy, the skin and subcutaneous tissues were dissected down to the level of the anterior rectus sheath on both sides of the defect, exposing the native fascia along the edge of the defect. After suturing 2 cm of the top and bottom edges of the native fascia lata, the fascia lata graft was used to reconstruct the remaining defect, which measured 12 × 6 cm. For placement of the graft, the fascia lata was sutured superficial to the edge of the defect with minimal overlap   [4].Two years later, the patient was readmitted because of recurrent tumors measuring 3.0 and 1.0 cm in the S5 and S7 subsegments of the liver, respectively. Preoperative magnetic resonance imaging (MRI) revealed the implanted fascia lata graft above the sheath of the rectus abdominis as an interpositional graft . Repeat Although prosthetic materials are commonly used to repair abdominal fascial defects, autologous tissue is preferred in the presence of contamination due to the risk of mesh infection. In such a situation, autologous tissue grafts have better adaptability and a lower risk of infection in comparison with prosthetic materials , 5. The Regarding the viability of fascia autografts, Peacock reported that none of the 17 patients who underwent the onlay imbrication technique suffered recurrences over an observation period of 2-5 years and that there were no indications of graft disintegration . Other cWound and mesh infections can be a grave complication in patients undergoing repair with prosthetic materials . If meshIn conclusion, the present case suggests that the status of an implanted fascia graft is the same as that of native fascia in terms of healing and resistance to contamination. Further studies are required to evaluate the long-term status of implanted fascial grafts. In our limited experience, we suggest that relaparotomy is safe after repair with a free fascia lata graft.


Kidney Donor Profile Index (KDPI) has been incorporated in the United States to improve the kidney transplant allocation system.To evaluate deceased kidney donors’ profile using KDPI and compare to the previous United Network for Organ Sharing (UNOS) definition of expanded criteria donors (ECD) and assess the KDPI applicability to predict five-year graft survival and renal function in our sample.Retrospective cohort of 589 kidney transplants from deceased donors performed from January 2009 to May 2013 with follow-up until May 2018.In 589 kidney transplants, 36.6% of donors were classified as ECD and 28.8% had KDPI ≥ 85%. Mean KDPI was 63.1 (95%CI: 60.8-65.3). There was an overlap of standard and ECD in KDPI between 60 and 95 and a significantly lower death-censored graft survival in KDPI ≥ 85% (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006. The AUC-ROC was 0.577 . Renal function at 5 years was significantly lower according to the incremental KDPI (p < 0.002). KDPI , donor-specific antibodies , acute rejection episode  were independent and significant risk factors for death-censored graft loss at 5 years.In our study, 36.6% were classified as ECD and 28.8% had KDPI ≥ 85%. KDPI score showed a moderate power to predict graft survival at 5 years. Renal function was significantly lower in patients with higher KDPI. The eligible population was all sequentially deceased donor kidney transplant recipients transplanted from January 2009 to May 2013 with a follow up until May 2018. Inclusion criteria were adult kidney recipients with at least 3 months of follow-up. We excluded kidney transplants (KTs) combined with another organ and all the cases with missing data necessary to calculate the KDPI scores. Clinical data from our local transplant database and medical records including baseline demographic characteristics from donors and recipients, transplant characteristics and clinical follow-up, return to dialysis, and death were collected. This study was undertaken following the principles stated by the World Medical Association Declaration of Helsinki and was submitted and approved by the Institutional Ethics Review Board.Our kidney allocation system followed the human leukocyte antigen (HLA) compatibility score as a major weight variable. The crossmatch was performed for all transplants by cytotoxicity and flow cytometry. Our acceptance criteria of older donors followed the UNOS ECD definition associated with the pre-implant biopsy results. The biopsy criteria included the ECD donor, acute renal injury and macroscopy abnormalities.https://optn.transplant.hrsa.gov/resources/allocation-calculators/kdpi-calculator)For analyses purpose, the donors were classified by the previous UNOS criteriaOur sample did not involve any donor with cardiac death because Brazilian law does not allow it. The delayed graft function was defined as the necessity of at least one dialysis session within the first week after kidney transplantation. Donor specific antibodies (DSA) were considered for mean fluorescence intensity above 1000 in the pre-transplant sera screening in all recipients. Definition of acute rejection episode was biopsy-proved. The immunosuppressive regimen does not differ between SCD and ECD . Induction therapy with antithymocyte globulin was used in presence of DSA, panel reactive antibody above 50%, and cold ischemia time > 24 hours. The graft failure was defined as return to dialysis, preemptive re-transplantation, or death with functioning graft. The graft survival, death-censored graft survival, and glomerular filtration rate (GFR) after one, three, and five years post-transplantation were the evaluated outcomes. GFR was estimated by the chronic kidney disease epidemiology (CKD-EPI) formulat-test or ANOVA. Actuarial graft survivals were performed by the Kaplan-Meier and log-rank methods. The assessment of risk for graft loss was performed by the Cox uni and multivariate analyses and shown as hazard ratios (HRs) with 95%CI. In the multivariate analysis we included only the variables with a p value < 0.05 in the univariate analysis. We also performed the receiver operational characteristic (ROC) curves for assessing the predictive ability of KDPI to estimate the death-censored graft-failure. The value defined as cut-off was determined by the maximum of Youden index (J = sensitivity + specificity − 1). A p value < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS V 23.0Qualitative variables are presented as frequency and percentage. Quantitative variables with a normal distribution are reported as mean and standard deviation (SD) or 95% confidence interval (95%CI). The differences between mean scores were analyzed by the student During the study period, 744 deceased donor kidney transplants were performed of which 589 transplants fulfilled the inclusion criteria. Recipients aged less than 18 years (n = 126) and the kidney transplants combined with other solid organs (n = 29) were excluded. The demographic data are shown in Kidney transplants from ECDs by the previous UNOS criteria were 36.3%, and 28.8% had KDPI ≥ 85%. The mean KDPI was 63.1 (95%CI: 60.8-65.3). When comparing donors according to the KDPI and UNOS criteria, all KDPIs inferior to 60 were considered as standard criteria donor (SCDs) and all KDPI that equaled or exceeded 95% were regarded as ECDs. There was an overlap of SCDs and ECDs in KDPI between 60 and 95% .The mean recipient age (years) in the KDPI categories was 0-20: 44.79 (95%CI: 41.1-48.4); 21-59: 45.45 (95%CI: 43.6-47.2); 60-84: 49.96 (95%CI: 48.2-51.7) and ≥ 85: 55.2 (95%CI: 53.6-56.8). There was a significant difference in recipient age between KDPI ≥ 60 and ≥ 85 when compared to KDPI < 60 . There was no significant difference when comparing recipient age with KDPI between 0-20 and 21-59%.The global graft survival according to KDPI is presented in There was also a significantly lower 5-year death-censored graft survival in KDPI ≥ 85 (78.6%); KDPI 0-20: 89.8%, KDPI 21-59: 91.6%, and KDPI 60-84: 83.0%; p = 0.006 .The AUC-ROC for graft loss was 0.577 . KDPI of 71% presented the best sensitivity (55.7%) and specificity (55.7%). The KDPI of 85% showed 39% sensibility and 73% specificity for 5-year death-censored graft loss.Kidney function at 1 and 5 years of follow-up was significantly lower with higher KDPI (p < 0.002) .The univariate analysis for the risk of death-censored graft loss is presented in The multivariate analysis is also shown in The previous UNOS criteria were not included in the multivariate analysis because they are strongly correlated with KDPI; thus, the 4 variables in the UNOS criteria for EDC were included in KDPI.,,,In our cohort, 36.3% of kidney transplants were from ECDs matching the UNOS criteria and 28.8% had KDPI ≥85%. In comparison, an US study found 17.3% ECD and 9.7% KDPI > 85%,,-,-Our study demonstrated a considerable overlap in the KDPI distribution between SCD and ECD categories also noticed by Rao et al. and Woodside et al. This overlap was in KDPI range between 60 and 95%-In our study, each KDPI increment of 1% was independently associated to 1% graft loss risk at 5 years in univariate as well as multivariate analyses. Arias-Cabrales et al. found 3% increase in the graft loss risk for each KDPI incrementDespite the acceptable graft survival results, the discard rates have increased in US, especially for high KDPI kidneys. From 2012 to 2014, 18.3% of available kidneys for transplant were discarded. The discard rates increased 50.6% for KDPIs > 80% and 71.6% for KDPI > 95%2 for KDPI < 20, 21-34, 35-85, and > 85%, respectively). The reduction rate was similar in the different groups during the follow-up; however, they included a GFR of 0 mL/min/1.73 m2 for patients with graft lossLehner et al. observed a GFR reduction as KDPI increased , which is similar to the results in the literature (C Statistic = 0.60 in the US). Thus, it is not precise enough to estimate with high confidence the quality of donors with close KDPI scores. Furthermore, the KDPI does not include other donor risk factors related to outcomes as pre-implant biopsies and kidney anatomical alterations . The KDPI also does not include the probability of cancer and infection transmissions, except hepatitis C. In our sample there was no donor with cardiac death because in our country it is not allowed.In our study, 36.6% of kidney donors were classified as ECDs and 28.8% had KDPI ≥ 85%. There was an overlap of ECD/SCD with KDPI scores between 60 and 95%. All KDPI scores above 95% were considered as ECDs.The KDPI score showed a moderate accuracy to predict graft survival at 5 years. For each KDPI increment point there was an increased graft loss risk of 1%. Recipient immunological variables were more accurate to predict graft survival.The GFR was significantly lower for higher KDPI scores at one and five years after transplantation. The KDPI calculator is available for free online and does not cause any delay in kidney allocation. It seems to be a useful tool to help in organ allocation, even though it was developed based only on the North American population.Ideally, there should be an equation based on Brazilian donors to apply in our population.