Schistosoma mansoni detection in humans, for the detection of intestinal livestock schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. POC-CCA, together with the circulating anodic antigen (CAA) test, miracidial hatching technique (MHT), Kato-Katz (KK) and organ and mesentery inspection , were applied to samples collected from 195 animals  from abattoirs and living populations) from Senegal. POC-CCA sensitivity was greater in the S. curassoni-dominated Barkedji livestock, both for cattle : 55%-98%) and small ruminants , than in the S. bovis-dominated Richard Toll ruminants . Overall, sensitivity was greater in cattle than in small ruminants. Small ruminants POC-CCA specificity was similar in both locations , whilst cattle POC-CCA specificity could not be assessed owing to the low number of uninfected cattle surveyed. Our results indicate that, whilst the current POC-CCA does represent a potential diagnostic tool for cattle and possibly for predominantly S. curassoni-infected livestock, future work is needed to develop parasite- and/or livestock-specific affordable and field-applicable diagnostic tests to enable determination of the true extent of livestock schistosomiasis.Schistosomiasis is a major neglected tropical disease (NTD) affecting both humans and animals. The morbidity and mortality inflicted upon livestock in the Afrotropical region has been largely overlooked, in part due to a lack of validated sensitive and specific tests, which do not require specialist training or equipment to deliver and interpret. As stressed within the recent WHO NTD 2021–2030 Roadmap and Revised Guideline for schistosomiasis, inexpensive, non-invasive, and sensitive diagnostic tests for livestock-use would also facilitate both prevalence mapping and appropriate intervention programmes. The aim of this study was to assess the sensitivity and specificity of the currently available point-of-care circulating cathodic antigen test (POC-CCA), designed for  Schistosoma mansoni in humans, we hypothesised that POC-CCA could be used to detect livestock intestinal schistosomiasis caused by Schistosoma bovis and Schistosoma curassoni. The aim of this study was to evaluate the sensitivity and specificity of POC-CCA for the detection of intestinal livestock schistosomiasis in Senegal. POC-CCA sensitivity varied by ruminant group and by parasite species/location, while POC-CCA specificity in small ruminants, at least, did not vary across populations. We conclude that, whilst the currently-available POC-CCA does represent a potential diagnostic tool for schistosomiasis in cattle, the factors determining test performance warrant further investigation and further livestock-specific assays would be ideal.Schistosomiasis is a neglected tropical and zoonotic disease, infecting over 230 million people and millions of animals worldwide. The potential contribution of livestock schistosomiasis to disease transmission in human populations has implications for the design of effective disease management and elimination programmes. However, our understanding of the true prevalence and impact of animal schistosomiasis is severely limited, in part due to a lack of accessible and accurate diagnostic tools. This need for sensitive and specific tools for animal schistosomiasis diagnosis has been recognised in the most recent WHO Guideline and NTD roadmap. As a point-of-care circulating cathodic antigen (POC-CCA) diagnostic test is now available to assess intestinal schistosomiasis caused by  The development and application of sensitive and specific diagnostic techniques for detection of infectious diseases is vital for the monitoring and evaluation of all treatment programs in endemic areas, especially whenever considering elimination and/or drug-resistance pharmacovigilance. Within this, point-of-care diagnostic testing is particularly needed wherever there is a necessity for a fast diagnostic outcome that is independent from sophisticated, time-consuming, labour-intense and/or expensive laboratory procedures . This neSchistosoma spp. blood-flukes. Approximately 90% of the 230 million people infected worldwide live in the Afrotropical region [Schistosoma species found amongst livestock in Africa are the intestinal Schistosoma bovis and Schistosoma curassoni in West Africa and Schistosoma mattheei in East Africa. These species are phylogenetically close to the human urogenital parasite Schistosoma haematobium and have been found to regularly form viable hybrids within humans, both across Africa [Schistosomiasis is one of the major debilitating NTDs/NZDs, caused by snail-borne dioecious l region –8. The ms Africa , and eves Africa , 15. Outs Africa , 17. Furs Africa .The recently launched WHO NTD 2021–2030 Roadmap and Guideline for the control and elimination of human schistosomiasis therefore poses the question of anti-schistosomiasis treatment of livestock across Africa in order to achieve the new targets of Elimination as a Public Health Problem (EPHP) in all 78 currently-endemic counties and Interruption of Transmission (IoT) in selected African regions by 2030 , 20. ThiT3: Test, Treat, Track design for livestock schistosomiasis in the Afrotropical region, which anchors the key recent WHO policy recommendations on diagnostic testing, treatment and surveillance in general.To promote sustainable livestock schistosomiasis prevention and treatment in the Afrotropical region, there is therefore a need to both easily and inexpensively diagnose animal schistosomiasis, and subsequently effectively treat only infected individuals and/or herds, such as through a targeted test-and-treat (TnT) or Schistosoma mansoni and Schistosoma japonicum infections) has recommended the formalin-ethyl acetate sedimentation-digestion with quantitative polymerase chain reaction, as the most promising field-applicable techniques in non-human animal hosts [There are, however, currently limited diagnostic techniques that can detect schistosomiasis in livestock with sufficient levels of sensitivity and specificity, as well as logistical ease, that can fully inform disease management decisions . Of thosal hosts , althougal hosts .Schistosoma spp. infections amongst humans [S. mansoni prevalence in endemic areas [S. haematobium infections with POC-CCA is less efficient i.e. to find the lower trematode burden infections [Tests for antigens, rather than antibodies, are preferred in endemic areas due to the lag in clearance of parasite-specific antibodies after infection subsides  and thert humans . Whilst t humans , 26, rapt humans , 28. Givic areas , 30. Thefections –34.S. mansoni infection in one non-human-primate study [S. bovis and S. curassoni (as well as S. mattheei) are intestinal schistosomes of livestock, and taking into account our recent social surveys which showed a demand amongst livestock owners within Western Africa [S. bovis, S. curassoni and their hybrids in Senegal, by host species, in relation to traditional and novel alternative parasitological and immunological diagnostic methods currently available, employing Bayesian latent class models.The POC-CCA has been used to assess te study ). Given n Africa , we predFor all primary data collection activities, the researchers first explained to the livestock owners and, for live-sampling collections, village leaders what the study was about, how the data collection would work and the rights of the participants. Following that, written consent was obtained from each participant. Ethical approval was sought and granted by: i) the Clinical Research and Ethical Review Board at the Royal Veterinary College; approval number URN 2019 1899–3; and (ii) the Comité National d’Ethique pour la Recherche en Santé  approval number SEN15/68 and SEN 19/68. Urine samples were imported from Senegal to the RVC in the UK with the import licence ITIMP19.0161 and from the UK to LUMC in the Netherlands with the import licence VGM_IN17-1416-GvW.Schistosoma snail intermediate host and human-livestock water contact points throughout the year, supporting the co-occurrence and interspecific interactions between S. haematobium, S. mansoni, and other Schistosoma spp. of veterinary importance [S. bovis and cattle is the most affected host species. The Barkedji area presents temporary water sources that disappear during the dry season, leading to important seasonal migration of livestock-keeping communities, and annual interruption in schistosomiasis transmission. Small ruminants are the most important livestock host species, infected by S. curassoni. However, both schistosome species and hybrids are present in the two areas and all livestock species can be found infected to a lesser extent. Full details on the infection prevalence amongst definitive and intermediate hosts, together with the habitat of two areas, can be found in [The study was conducted in Senegal, West Africa. Cross-sectional livestock parasitological surveys were conducted from May to August 2016 and from October 2017 to January 2018 in two areas located in the north of the country; the town of Richard Toll, in the Senegal River Basin, and villages around the Lac de Guiers (area hereafter referred to as Richard Toll), and the town of Linguere and villages around Barkedji along the Vallée du Ferlo (area hereafter referred to as Barkedji). Following the construction of the Diama Dam in 1986, situated on the Senegal River over 100 km downstream from Richard Toll, the environment surrounding this location has undergone important permanent alterations. Desalination, creation of irrigation canals and of permanent freshwater bodies have facilitated the expansion of portance –38. The Schistosoma spp. adults  and those found were stored in RNA-later for molecular analysis (see Sections 1 and 2 in Schistosoma spp. eggs via two Kato-Katz (KK) slides and MHT  that was based on three additional diagnostic methods, namely MHT, KK and UCAA. CRS is based on a combination of tests with moderate sensitivity and high specificity . CRS resWe then developed a Bayesian latent class model (BLCM) to assess the sensitivity and specificity of POC-CCA for the detection of active schistosomiasis in both large (cattle) and small (sheep and goats) ruminants –43 that Latent class models (LCM), as proposed by Hui and Walter , involveConditional independence of POC-CCA and CRS in the two-test model was assessed in two ways. Firstly, the Deviance Information Criterion (DIC)  of modelThe beta prior distributions  by means of the JAGS “step” function , 52. WheDirect diagnostic of schistosomiasis in abattoir animals enabled us to determine whether animals were infected with adult trematodes and miracidia. Two-test independence models were applied to these data and POC-CCA results. This enabled us to estimate POC-CCA sensitivity in abattoir animals and to assess whether CRS-derived and direct diagnostic-derived sensitivities differed. Sensitivity and specificity for direct diagnostic were considered to be 99%.Statistical analyses were carried out in R  version S. curassoni, whilst animals from Richard Toll shed mainly S. bovis eggs  nor in small ruminants . Consequently, in all subsequent analyses, no distinction was made between blood-positive or negative samples.The cross-tabulated results for CRS and POC-CCA are shown in BLCM results from the two-test dependence and two-test independence models, by site and ruminant group , indicatPOC-CCA sensitivity in Barkedji was 81% (95% CrI: 55% to 98%) and in Richard Toll it was 62% (95% CrI: 41% to 84%). As the probability that the sensitivity in Barkedji was greater than in Richard Toll was high  and in Richard Toll it was 12% (95% CrI: 1% to 37%) see . The proPOC-CCA specificity in Barkedji was 91% (95% CrI: 73% to 99%) and in Richard Toll it was 88% (95% CrI: 65% to 99%). The probability that the specificity in Barkedji was greater than in Richard Toll was 0.60. The overall specificity was 91% (95% CrI: 77% to 99%).S. curassoni was the main parasite species, and better than KK but worse than MHT in Richard Toll cattle, where S. bovis was the main parasite. POC-CCA sensitivity performed worse than MHT and KK in Richard Toll small ruminants.Visual comparisons  of the aThe results of the prior sensitivity analyses indicate that the baseline prior models adopted were robust and that the priors were not exerting an unduly effect on the POC-CCA accuracy estimates , their pregnancy status, and whether or not they have haematuria or a urogenital infection , 59.POC-CCA accuracy has been found to vary depending on production batch, raising questions regarding production quality control and calls for the optimisation and standardisation of production –62. ThisS. curassoni and S. bovis detection, respectively. However, this need to be further investigated. The observed high probabilities of sensitivity differences point to novel evidence of variation between host and parasite species that can inform the design and analyses of future diagnostic evaluations.Due to the absence of a gold-standard diagnostic test for livestock schistosomiasis, this study derived a composite reference standard (CRS) that was based on KK, MHT and UCAA results. The sensitivities of KK and MHT are relatively low, partly due to the technical difficulties associated with the management of large volumes of faecal material. These methods are highly specific, although misclassification of eggs and miracidia can occur. On the other hand, UCAA assays had been labelled as ultrasensitive for human schistosomiasis detection , 63, butOverall, our results indicate that the current POC-CCA developed for human use does represent a potential diagnostic tool for schistosomiasis in livestock populations. However, the observed variation in test performance across host species, parasite species and sites does have implications for the broader applicability of this diagnostic method, as it may hinder our ability to establish universally valid thresholds for disease prevalence that inform control programmes. Hence, the factors that determine test performance need to be investigated further so that region-specific guidelines could be derived if needed. Likewise, manufacturers quality control must be a foremost priority if POC-CCA diagnostic tests are implemented for the assessment of schistosomiasis, both in humans and animals. In order to move towards the interruption of transmission, the elimination of this zoonotic transmitted disease , 3 and tS1 Appendix1. Description of diagnostic tests. Table A. Summary of diagnostic tests and definitions of positive results. 2. Molecular analyses for Schistosoma species determination. 3. Statistical analysis. Table B. Diagnostic tests and covariance setting included in the models studied. Table C. Baseline priors used in multivariate modelling. 4. Observed prevalence. Table D. Summary statistics by diagnostic method: number of infected animals/number of animals examined , by site (S), ruminant group (R) and animal population (P). 5. Distribution of Schistosoma species. Table E. Number of animals genotyped and number of animals in each combination of Schistosoma species. 6. BLCM sensitivity. Table F. Priors adopted in the sensitivity analysis, modifying CRS priors (A) and prevalence priors (B). Table G. BLCM results from 2-tests independence analyses showing parameter median (95% CrI) and models’ deviance information criterium (DIC), for POC-CCA sensitivity  and specificity , comparing baseline priors, CRS modified priors and prevalence modified priors. 7. Comparison of sensitivity and specificity in live and abattoir populations. 8. Models JAGS code. 9. References. 10. Data.(DOCX)Click here for additional data file.


Mental health problems among adolescents have been on the rise particularly among adolescents in sub-Saharan Africa (SSA) due to impoverished living conditions and a high burden of chronic diseases including HIV/AIDs. COVID-19 pandemic has further exacerbated the risk and placed additional stress on adolescents’ mental health. While the burden might be high, there are fewer mental health services in the region.To evaluate the psychological and mental well-being of adolescents living in and co co-design with civil society organizations (CSOs) interventions aimed at enhancing mental health and psychosocial well-being.Firstly, we conducted a formative phase to assess the burden of various mental health problems in Kenya. We conducted a cross-sectional survey in which we assessed the mental health status of 1541 adolescents using standardized tools. The participants comprised in and out of school adolescents, adolescents with disability, and those living with HIV/AIDS. Furthermore, we undertook a qualitative study through FGDs and KIIs to identify the factors contributing to mental health problems.Secondly, we aim to adapt interventions that seek to promote mental health. Finally, we aim to implement effective mental health interventions targeting over 2000 adolescents living in Kenya’ informal settlements.We found the prevalence of depression to be higher among out-of-school adolescents at 36.0% compared to school-going adolescents at 20.6%. Furthermore, out-of-school adolescents had statistically significantly higher anxiety scores as well at 27.7 % when compared to their school-going counterparts at 19.1%. In-school adolescents had a better quality of life scores, lower pandemic anxiety scores, and lower emotional scores compared to their out-of-school counterparts. Results from regression models indicated that being out of school, having a COVID-19 infection, having poor relationships with parents and peers, loneliness, and living in an unsafe neighborhood were factors associated with poor mental health outcomes. During the qualitative interviews, participants noted that COVID- 19 brought about financial stress, joblessness, led to early pregnancies, involvement in commercial sex work by adolescents, school dropouts, lead to stress, and depression among other issues.Image 3:Adolescents, especially those out of school are at a high risk of poor mental health outcomes due to exposure to a host of psychosocial risk factors. We have identified two interventions that we are keen to implement: the Shamiri Wellness Intervention (https://www.shamiri.institute/the-shamiri-intervention) and the Mental Health Literacy Programme . We hope that by working with CSOs, the study will support the development of their capacity to offer mental health services that are sustainable, and contextually appropriate.None Declared


Preoperative renal dysfunction is associated with mortality in patients with acute type A aortic dissection (ATAAD) repair. However, the long-term outcome of chronic kidney dysfunction (CKD) in ATAAD is unclear. The study aimed to evaluate the long-term outcome of CKD in patients with ATAAD repair. We retrospectively studied patients with ATAAD repair using data from the Taiwan’s National Health Insurance Research Database between July 1, 2004, and December 31, 2013. The outcomes of interest included all-cause mortality, readmission due to any cause, redo aortic surgery, major adverse cardiac and cerebrovascular events, and liver and renal outcomes. There were 3328 patients who received ATAAD repair. These patients were divided into CKD and non-CKD groups. In-hospital mortality in the CKD group was significantly higher than that in the non-CKD group . During long-term follow-up, patients with CKD had higher risks of all-cause mortality including in-hospital death , mortality after discharge , and readmission rates . However, no significant difference was observed between the dialysis and non-dialysis groups. On the basis of our results, patients with CKD carry a poor long-term outcome after ATAAD repair. Cardiac surgeons should be aware of this condition when dealing with ATAAD repair. CKD patients are prone to major cardiovascular comorbidities, including coronary artery disease, valvular disease, and arrhythmia, and may require cardiovascular surgery, which is classified as a high-risk procedure.,3 Therefore, the impact of CKD on cardiovascular surgical outcomes is worthy of attention.Chronic kidney disease (CKD) is progressively increasing in Taiwan, including end-stage renal disease (ESRD) requiring renal replacement therapy. Additionally, in data from the Japan Adult Cardiovascular Surgery Database, CKD patients were susceptible to high mortality and morbidity after coronary artery bypass grafting, which were dramatically increased in patients on dialysis. In particular, acute type A aortic dissection (ATAAD), a cardiovascular emergency in need of surgical approaches with different complexities, carries critically high mortality and morbidity despite advancing medical management and surgical techniques. Akiyoshi et al conducted a 2-center retrospective cohort of 960 patients undergoing emergent repair of ATAAD and identified increased 30-day mortality and in-hospital death in dialysis patients compared with the non-dialysis group. However, no literature has reported on the long-term outcomes of CKD in the surgical treatment of ATAAD. Therefore, we conducted a nationwide population cohort study to analyze the long-term outcomes of surgical treatment of ATAAD in CKD patients.Data from United States Renal Data System database revealed poor long-term postoperative outcomes of thoracic aortic interventions for patients with ESRD, regardless of whether an open surgical or endovascular modality is adapted.This national population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD). The NHIRD is a national population administrative database that contains health insurance claims data from a single-payer National Health Insurance (NHI) program operated by the government, with a coverage rate of > 99%. The Bureau of NHI began issuing all electronic claims data to the public under the NHIRD program in 1999. Disease diagnoses are based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). This study was evaluated and approved by the Chang Gung Memorial Hospital Ethics Review Committee (IRB: 104-7990B), and the informed consent was waived because this was a retrospective study.From the NHIRD, we obtained the medical claims data sets of inpatients admitted to NHI-contracted hospitals for treatment of ATAAD between July 1, 2004, and December 31, 2013. Patients with a principal diagnosis of aortic dissection (ICD-9-CM: 441.0) were included. Patients who previously had aortic dissection, were treated for type B aortic dissection, received medical therapy instead of surgical intervention and were <20 years old were excluded. In total, 3328 patients who received surgical treatment for ATAAD with ascending aorta replacement, aortic arch replacement, aortic root replacement, or elephant trunk were eligible for analysis. Next, according to the diagnosis of CKD (ICD-9-CM codes: 585.1–585.6), these patients were separated into CKD and non-CKD groups , comorbidities, hospital level, hospital volume of type A surgery, and surgical year. We utilized the ICD-9-CM diagnostic or procedure codes and the Taiwan NHI reimbursement codes to obtain baseline characteristics and surgical details of the patients based on inpatient claims data. Comorbidities and Charlson Comorbidity Index (CCI) scores were detected using previous inpatient diagnoses, which can be tracked to the year 1997. The disease codes are provided in Table S1, Supplemental Digital Content, http://links.lww.com/MD/I975. Late outcomes were all-cause mortality, readmission due to any cause, redo aortic surgery and major adverse cardiac and cerebrovascular events. Major adverse cardiac and cerebrovascular events were composed of myocardial infarction, heart failure or stroke. Mortality was defined by a withdrawal from the NHI program. Redo aortic surgery was extracted by Taiwan NHI reimbursement codes. The occurrence of acute myocardial infarction, heart failure admission or stroke was defined as the principal diagnosis of admission, where the diagnostic codes have been validated in previous NHIRD studies. Each patient was followed until death or December 31, 2013, whichever came first.The study outcomes included in-hospital outcomes and late outcomes, which were detected by the ICD-9-CM diagnostic or Taiwan NHI reimbursement codes. Details of the ICD-9-CM diagnostic codes can be found in Table S1, Supplemental Digital Content, A propensity score matching (PSM) method was employed in this study to reduce selection bias between the CKD and non-CKD groups. The propensity score was the predicted probability to be in the CKD group given values of covariates using the logistic regression. The variables selected to calculate propensity score are listed in Table t test or the chi-square test) were performed and further introduced those variables with a P value < 0.2 in the univariable analyses into the multivariable Cox analysis with backward selection. A 2-sided P value < .05 was considered to be statistically significant, and no adjustment of multiple testing (multiplicity) was made in this study. All statistical analyses were performed using SAS version 9.4 , including the procedures of “psmatch” for propensity score matching and “phreg” for survival analysis.In-hospital categorical outcomes between groups were compared by conditional logistic regression analysis, in which the matching pairs were stratified to account for the outcome dependency within the same matching pair. In-hospital continuous outcomes between groups were compared by the linear mixed model, where the 2 patients within the same matching pair were considered to be correlated. Regarding time to event outcomes, the mortality rates between groups were compared by a Cox proportional hazard model. The incidences of nonfatal outcomes between groups were compared by the Fine and Gray subdistribution hazard model, which considered death as a competing risk. The correlation among patients within the same matching pair was accommodated by using the robust standard error  in the survival analyses. Study group (CKD vs non-CKD) was the only explanatory variable. In a further subgroup analysis of comparing groups of renal function  on all-cause mortality, we performed a Cox model with multivariable adjustments for age, sex, extension of aortic surgeries and concomitant surgeries. To investigate the risk factors of all-cause mortality, univariable analyses . After matching, there were no substantial differences in the baseline characteristics between the groups , except for mild differences in atrial fibrillation, elephant trunk and concomitant coronary artery bypass graft  . Preoperative CKD was also associated with higher risks of respiratory failure and de novo dialysis. Patients with CKD had higher transfusion rates, longer ICU stays, longer hospital stays and greater in-hospital costs , mortality after discharge , and readmission rates  ,,13 This observation has been confirmed in other study and has established preoperative renal dysfunction as an independent risk factor for late outcome after cardiac surgery. However, the impact of preoperative chronic renal dysfunction on the late outcome of aortic dissection treatment has not been investigated thoroughly. In a study in patients with CKD, it was observed that open thoracoabdominal aortic aneurysm repair carried a worse late outcome than in those without CKD. Our study has added to that work by demonstrating a higher risk of all-cause mortality in CKD patients after ATAAD surgery. In addition, old age, impaired renal function, stroke, liver cirrhosis, coagulopathy, aortic root replacement, and concomitant coronary artery bypass graft were potential risk factors for all-cause mortality after surgical treatment of ATAAD. Multiple focal or diffuse aortic wall calcifications and accelerated atherosclerosis in CKD patients had a chance of aortic dissection and had a trend of higher risk for redo aortic surgery. Moreover, CKD was associated with immune dysregulation and infection, including graft infection. These conditions were associated with higher all-cause mortality and readmission to the hospital after ATAAD repair.Most of the literature demonstrated that preoperative chronic renal dysfunction reduced long-term survival after cardiac surgery. In their study, a small number of dialysis patients were compared with non-dialysis patients including those with normal GFR and chronic renal insufficiency without dialysis. In our study, we compared the all-cause mortality in patients without CKD, non-dialysis CKD and dialysis CKD in the follow-up period. The 2 CKD groups had higher mortality rates than the non-CKD group; however, no significant difference was observed between the dialysis and non-dialysis groups. Further large-scale prospective studies are needed to assess the long-term results of ATAAD surgery between dialysis and non-dialysis patients.The long-term surgical outcomes of ATAAD in patients with ESRD have not been well investigated. A previous study found that the 6-year survival rate was lower in the dialysis group than in the non-dialysis group in patients who underwent ATAAD repair.This study has several limitations, primarily due to the use of the NHIRD database from Taiwan. First, the NHIRD does not contain disease-specific information including aneurysm-specific data such as size, extent, or morphology. In addition, the diagnosis of CKD was according to the ICD-9 code, instead of measuring the estimated glomerular filtration rate. Different stages of the CKD were unable to classify using ICD-9 code. Because of higher rate of end-stage renal disease in our CKD cohort, and different stages of the CKD were unable to classify using ICD-9 code, we couldn’t explore whether preoperative lower stage CKD will lead to a higher rate of complications and worse long-term outcome after surgery for ATAAD.Future study was warranted to evaluate the effect CKD stage on outcomes in this population. Second, it is unlikely to assess the reasons for readmission. Nevertheless, because of the link between outpatient clinic and hospital admissions and the NHIRD database, we can overcome the lack of specific accurate data by investigating the exact reasons for readmissions. Third, our study covered a long time period during which surgical techniques and intensive care medicine facilities have improved. And the question of whether high or low volume centers regarding outcomes still remains. To address these questions, we employed a propensity score matching to reduced selection bias between the CKD and non-CKD groups. Furthermore, we could not identify the newly-onset preoperative renal dysfunction complicated by the aortic dissection, or the irreversible deterioration of renal function due to the aortic disease or treatment/surgery, apartment from the CKD which already existed before the onset of aortic dissection. and we believe that the strengths of our study still provide a significant contribution to the analysis of outcomes of ATAAD surgery in CKD patients. However, a prospective randomized trial is still required to assess the long-term results of ATAAD repair in CKD patients.Finally, although PSM minimized measured confounders in this retrospective study, unmeasured and unknown confounders still exist; therefore, we can only indicate association instead of causation. Despite these limitations, the prevalence and incidence of CKD in Taiwan are relatively high compared with those in other countries,In conclusion, patients with CKD carry considerable risks for poor short- and long-term outcomes compared to patients without CKD after ATAAD repair. Patients with CKD face a substantial risk for perioperative complications including in-hospital mortality and adverse events. During long-term follow-up, CKD patients had a higher risk of all-cause mortality and readmission due to any cause, as well as a trend of higher redo aortic surgery. Preoperative counseling, optimizing kidney protection during surgery, and close surveillance of renal function after surgery play an important role in improving the short- and long-term outcomes of ATAAD repair for these patients.The authors thank Alfred Hsing-Fen Lin and Zoe Ya-Jhu Syu for their assistance in statistical analysis.Conceptualization: An-Hsun Chou.Data curation: An-Hsun Chou, Meng-Ling Hsieh, Yu-Sheng Lin, Dong-Yi Chen, Pao-Hsien Chu.Formal analysis: An-Hsun Chou, Meng-Ling Hsieh, Yu-Sheng Lin, Dong-Yi Chen, Pao-Hsien Chu.Writing – original draft: An-Hsun Chou.Writing – review & editing: Shao-Wei Chen.


No other investigated factors were significantly associated with VQoL. The final quantile regression model included functional vision scores and the presence of additional health condition. Variation in self-reported VQoL in CYP-VI can be partly accounted for by factors relating to the clinical status of the affected child and, more importantly, by non-health-related factors. This needs to be considered in clinical practice when assessing vision-specific outcomes and providing support to CYP-VI, as well as in the development of future interventions.Childhood visual impairment can have a significant impact on an individual’s development. To improve clinical care and develop appropriate psychosocial interventions of these patients, it is necessary to understand the contributing and modifiable factors that both identify individuals in greater need and could be targeted in interventions. Here we investigate the broader individual, family, and environmental factors associated with vision-related quality of life (VQoL) of children and young people with visual impairment (CYP-VI). Data for this cross-sectional study were collected from September 2014 to May 2017 to develop and validate two vision-specific patient-reported outcome measures (PROMs) for CYP-VI. Patients were recruited from 22 hospitals in the United Kingdom and were aged 7–18 years with visual impairment as per WHO criteria. Participants self-completed the two PROMs, VQoL and Functional Vision Questionnaires. Clinical characteristics were extracted from medical records. Their carers provided information on family sociodemographic backgrounds. Associations between the VQoL scores and other factors were examined using Spearman’s correlation, Kruskal-Wallis, Wilcoxon rank-sum tests, and quantile regression models. The sample consisted of 152 CYP-VI . Better VQoL was significantly associated with better functional vision overall ( VI) in childhood, while uncommon [CYP-VI) may be at risk of impaired quality of life (QoL) [Vision has a vital role in early human development –3. Thus,uncommon , presentuncommon , 6. Howeuncommon . Some chfe (QoL) , 8, poorfe (QoL) , low selfe (QoL) , and poofe (QoL) –17. CYP-fe (QoL) , 18–21.The paediatric literature on other chronic health conditions indicates that individuals with severe disabilities or conditions can report good psychosocial QoL regardless of their impairments –27. It aPROMs) are increasingly used to evaluate holistically the impact of a health condition on the patient’s life from their own perspective [VQoL) [FV) [Patient-Reported Outcome Measures (spective –44. Two e [VQoL) , 40 and oL) [FV) , 42. TheWe used data collected from a representative sample of CYP-VI who completed these age-specific vision PROMs , 42 duriData were collected between September 2014 and May 2017 as part of a larger programme of research developing and validating age- and stage-appropriate vision-specific PROMs for CYP-VI aged 8 to 18 years, specifically for the final phase of validation through a large-scale cross-sectional postal survey , 42.The study was approved by the National Health Service Research Ethics Committee for Essex and East of England, United Kingdom (REC 12/EE/0455) and followed the tenets of the Declaration of Helsinki. The analysis presented here was part of the original ethics approval. All participants gave informed written consent if ≥16 years or informed written assent if <16 years alongside informed written parental consent. Participation in this study was voluntary.LogMAR) or worse (worse than 6/18 Snellen), or additional visual defects causing VI as a result of any visual disorder. Those with other significant impairment that would prevent them from self-reporting and, therefore, self-completing the PROMs were not eligible. The achieved sample of 152 CYP-VI was representative of the overall target group in the United Kingdom (UK) with respect to sociodemographic and clinical characteristics [Patient identification and recruitment for this study have been reported in detail previously , 42. Pareristics . All werVQoL_CYP [FVQ_CYP) [CYP-VI self-completed the two age-appropriate PROMs  . The VQoBoth PROMs have been validated and calibrated using Rasch measurement theory  with theParticipants’ age, gender, and clinical characteristics were retrieved from the hospital electronic records and used with their  consent. The child’s parent or main carer reported on the family and other sociodemographic characteristics using a structured family background questionnaire developed for this study. Detailed information on how these data were coded for the analysis can be found in A study pack with invitation letters, the age-appropriate child/young person and parent information sheets, consent and assent forms, and the age-appropriate instruments version in large print were sent to the participants by post. Completed consent/assent forms and the questionnaires were returned to the research group using a postage-paid envelope also provided within the study pack.Analysis was performed in R (version 4.1.2 GUI 1.77)  on RstudClinical factors considered in the analysis were severity of VI, timing of onset of vision loss, rate of deterioration of vision, and presence of additional chronic conditions or impairments affecting the child’s development.Sex, age, and ethnicity of the child were considered alongside family structure, carer’s age, ethnicity, education, employment status and occupational level, number of siblings, birth order of the participating child, carers’ and siblings’ VI and health status. School type was considered as a broader environmental factor.IMD) based on the UK postal code [Socio-economic status was analysed using housing tenure, number of cars owned, and the index of multiple deprivation .z-scores for skewness and kurtosis was used to assess the distribution of VQoL_CYP and FV_CYP scores. D’Agostino’s K2 test showed both VQoL_C  and FV_CYP  scores were not normally distributed.Normality test using The self-reported VQoL scores stratified by participants’ demographic, familial and clinical characteristics are shown in rSpearman = –0.52, p < .001), showing CYP-VI who reported better VQoL also often reported less FV difficulties. CYP-VI with severe VI or blindness reported significantly more FV difficulty  but not significantly worse VQoL  than CYP with moderate VI  [VQoL and FV scores were significantly negatively associated (n study) , 42.p = .02, dCohen = 0.41) and VQoL scores , indicating CYP-VI who had one or more additional diagnoses (n = 26) reported worse VQoL and more FV problems than those without an additional diagnosis (n = 110).The presence of additional diagnoses affecting a child’s development was associated with both FV scores  and carer’s education level , demonstrating CYP-VI with less educated carers and living in areas with lower IMD quintile rank usually reported worse VQoL. Carer’s education level was also significantly associated with FV scores , indicating CYP-VI with less educated parents also reported more functional vision difficulties.Furthermore, VQoL scores significantly correlated with the IMD quintile rank (n = 125) reported significantly better VQoL  and FV  compared to CYP-VI enrolled in other types of school (n = 9).CYP-VI attending mainstream school  and prioritising potential targets for interventions to improve VQoL outcomes of these patients, thereby improving personalised care. The value of PROMs lies in their ability to capture the broader impact of living with a visual disability from the perspective of CYP-VI and in identifying the impact of age- and condition-specific challenges they experience.Limitations of this study relate to its use of data previously collected within a broader research programme, which means there was limited power for statistical analysis of some variables of interest, such as subsamples of CYP-VI with additional diagnosis or those not attending mainstream schools. As the data were collected via a postal survey, there is no knowing if carers influenced self-reporting by CYP-VI. Finally, the cross-sectional design means we cannot infer causality, which could be addressed in future longitudinal studies. The strengths of this study are the assessment of a large number of pre-specified potential associated variables with VQoL, including individual, family, and broader environmental factors and the use of robust validated PROMs to capture a secure measure of the impact of VI in childhood.CYP-VI with better self-assessed VQoL also reported better self-perceived functional vision . HoweverIn accordance with previous findings , we founSimilar to prior reports , 38, ourThe finding that CYP-VI in mainstream schools  experienced better VQoL than CYP-VI who were home-schooled or enrolled in a specialist and other types of school is interesting and concords with previous research showing that CYP-VI in specialist schools had worse daily living skills, social skills , and lowEven though it may not be possible to directly target factors such as, for example, living in more deprived areas or multi-morbidity, it is important to be mindful of these potential risks when designing interventions and allocating resources. Our findings show that interventions aimed at improving quality of life of CYP-VI should consider targeting resources at families of CYP-VI with more complex healthcare and clinical needs and those from lower socioeconomic groups. In the light of the recent COVID-19 pandemic, the cost-of-living crisis, and the higher incidence of VI in families living in the most deprived areas , furtherFrom a clinical perspective, ensuring multidisciplinary support and providing a personalised approach to the specific healthcare needs of patients at higher risk may modify or eliminate the potential negative impact of the risk factors . This requires further research to examine if such interventions and considerations would be helpful. Nevertheless, our findings demonstrate markers that clinicians can use to identify those amongst their patients who are likely to be at greatest risk of lower quality of life and, therefore, potentially in greatest need so that they are able to direct these patients to existing resources and services.Overall, as the impact of childhood VI may vary significantly across CYP-VI, there is a need for a more personalised approach to their care. The VQoL_CYP and FVQ_CYP are validated tools that can be easily utilised in routine clinical practice to monitor these patients’ outcomes  by assesIn conclusion, our study identifies that certain CYP-VI are at greater risk of experiencing poor vision-related quality of life. Socio-economic factors are at least as important as the clinical factors that healthcare professionals usually consider when thinking about which patients may need additional attention or support. Multidisciplinary teams have an important role in meeting the needs of affected children and their families to help them achieve better VQoL, especially in providing personalised care. School presents an important context for CYP-VI, and further research examining the impact of school setting on VQoL is warranted. Research to improve VQoL should consider clinical  as well as broader family and socio-economic determinants as potential targets for intervention.S1 FileThis supplemental material has been provided to give readers detailed information about the coding of the answers that parents/carers provided in the family background questionnaire.(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.


This cross-sectional study examines cost-sharing for ICU and non-ICU hospitalizations among adults with employer-sponsored insurance. Given that ICU care is expensive and US patients face increasingly large deductibles that generally reset each calendar year, out-of-pocket costs for ICU care may be large at the beginning of the year.STROBE reporting guidelines.We examined 2010 to 2019 adult hospitalization data from MarketScan commercial database, which contains a large, nationwide convenience sample of commercially insured individuals. The Harvard Medical School Institutional Review Board approved this cross-sectional study. We followed the We identified ICU admissions using revenue codes that indicated delivery of ICU services  and other plan types .Two-sided We identified 303 792 ICU and 2 043 619 non-ICU hospitalizations of commercially insured adults in December and January from 2010 to 2019. Among aggregate ICU hospitalizations, total cost-sharing averaged $1079 in December and $1871 in January, a 73.4% increase. Among non-ICU hospitalizations, total cost-sharing averaged $1043 in December and $1683 in January, a 61.3% increase . These iWhile resetting of the deductible was a factor in the December-to-January cost-sharing increase among HDHPs, higher coinsurance explained the cost-sharing increase among other plan types. The Hospitalizations, especially ICU admissions, are often unpredictable. We found large cost-sharing increases annually from December to January 2010 to 2019 for both ICU and non-ICU hospitalizations, within the same DRGs, and adjusted for observable patient factors (as patients were newly exposed to higher out-of-pocket costs at the beginning of the year). These increases were larger for ICU vs non-ICU hospitalizations and for patients with HDHPs vs other plans. Over the course of 1 year, cost-sharing for hospitalizations decreased by more than 50%, depending on plan type and whether admission included an ICU stay.4 Thus, these results resonate with recent reports of the benefits of resetting out-of-pocket costs or deductibles at shorter intervals throughout the year.6 Additionally, as the value of care commands greater attention from payers and policy makers, these findings underscore that inappropriate or low-value hospitalizations at the beginning of the year, particularly those involving ICU services, place a large financial burden on patients. A study limitation was the focus on hospitalizations of patients with employer-sponsored insurance; thus, the findings may not be generalizable to other populations.These findings highlight a shortcoming of deductibles that are scheduled to reset at the beginning of the calendar year, which likely has unequal consequences for different patients. Patients with lower incomes and HDHPs, for example, are more likely to use acute care and least able to handle unexpected emergency expenses.


Human histology provides critical information on the biological potential of various regenerative protocols and biomaterials, which is vital to advancing the field of periodontal regeneration, both in research and clinical practice. Outcomes of histologic studies are particularly valuable when interpreted considering additional evidence available from pre-clinical and clinical studies. One of the best-documented growth factors areproven to have positive effects on a myriad of oral regenerative procedures is recombinant human platelet-derived growth factor—BB (rhPDGF-BB). While a systematic review of clinical studies evaluating rhPDGF in oral regenerative procedures has been recently completed, a review article that focuses on the histologic outcomes is needed. Hence, this communication discusses the histologic effects of rhPDGF-BB on oral and periodontal regenerative procedures, including root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration. Studies from 1989 to 2022 have been included in this review. Periodontal tissue engineering requires three basic elements: cells, scaffolds/matrices, and signaling molecules (growth factors) . Cells sGrowth factors are molecules secreted by cells and are capable of stimulating a variety of cellular activities, including cell proliferation, migration, differentiation, and multicellular morphogenesis during both embryonic development and tissue healing and repair. Identified in the 1970s as a serum growth factor for multiple types of cells ,4,5, plaAt injury sites, platelets in the blood clot release α-granules containing PDGFs, which in turn attract and induce chemotaxis and the proliferation of a multitude of cells important in healing and bone regeneration, including periodontal ligament cells, mesenchymal stem cells (MSCs), and osteoprogenitor cells, as well as neutrophils and macrophages . The latWithin the context of this manuscript, the effects of PDGF-BB on periodontal regenerative procedures, namely root coverage and soft tissue augmentation, intrabony defects, furcation defects, peri-implant bone augmentation, and guided bone regeneration, are summarized from studies that evaluated the histologic evidence in humans and animal models . StudiesLynch et al. were the first to evaluate the effects of PDGF on periodontal and peri-implant regeneration. In a series of studies, they compared the histologic outcomes of open flap debridement to PDGF alone or in combination with insulin-like growth factors in terms of the regeneration of the soft and hard tissues of the periodontium in beagle dogs with naturally occurring periodontal disease ,34. TheiFurthermore, the influence of PDGF-BB on the initial periodontal cellular response was investigated by Wang et al. on a mongrel dog model over 1, 3, and 7 days . A closeSculean and coworkers studied the effect of PDGF on the regenerative potential of the connective tissue fibers of the periodontium . The stup < 0.05) regeneration of NA (69.6 + 12.0%) at 12 weeks. Treatment with PDGF-BB/IGF-I resulted in 21.6 +/− 5.1% and 42.5 +/− 8.3% ODF at 4 and 12 weeks, respectively, and 64.1 +/− 7.7% and 74.6 +/− 7.4% NA at 4 and 12 weeks, respectively . The results from this study demonstrated that: (1) OFD does not result in new attachment or periodontal regeneration in non-human primates; (2) IGF-I alone also did not significantly alter periodontal wound healing; (3) PDGF-BB alone did significantly stimulate NA, with strong trends for promoting bone fill; and (4) the PDGF-BB/IGF-I combination resulted in significant increases in NA and bone defect fill above OFD at both 4 and 12 weeks. This study led to the focus of further research on the use of rhPDGF-BB (without IGF-I) with various bone graft materials.Giannobile  and co-wFollowing those observations on animal models, Nevins and co-workers tested the effectiveness of three different concentrations of recombinant PDGF (rhPDGF-BB)  on individuals with periodontal disease for the first time . Teeth sHuman histological studies were subsequently performed to provide further evidence for periodontal regeneration in intrabony defects by testing different concentrations of PDGF. A study evaluated the histological outcomes of the combination rhPDGF-BB + b-TCP in the treatment of intrabony defects in eight periodontally-diseased patients . Two difIn 2010, Shirakata et al. evaluated basic fibroblast growth factor (bFGF), enamel matrix derivative (EMD), rhPDGF-BB + b-TCP, and control of open flap debridement (OFD) in the treatment of two-wall intrabony defects in beagle dogs, where each defect was treated with one of the treatments in each dog for 8 weeks . The resHistological evaluation of rhPDGF-BB in molar class II furcation defects was performed by Nevins and co-workers in the study that was discussed earlier in this review . HistoloA clinical study on humans by Camelo et al. evaluated the histological outcomes of rhPDGF-BB combined with DFDBA for the treatment of class II furcation defects . Two conHuman histological studies were subsequently performed to provide further evidence for the periodontal regeneration of class III furcation defects using rhPDGF-BB/b-TCP . Four paA split-mouth, randomized clinical trial by McGuire et al. compared coronally advanced flap with rhPDGF-BB + β-TCP  + bioabsorbable collagen wound dressing and coronally advanced flap with connective tissue graft . They teSimion et al. then tested the effect of using a rhPDGF + collagen matrix (CM) on soft tissue augmentation around dental implants in the esthetic region . FollowiAn evaluation of rhPDGF in ridge augmentation around dental implants was performed in a proof-of-concept study conducted by Simion et al. in a canine model . In thisThe question of whether a membrane is needed, beneficial, or inhibitory to rhPDGF-mediated regeneration was further evaluated by Al-Hazmi and co-workers . The aimStudies histologically evaluating the use of rhPDGF-BB for the augmentation of extraction sockets for implant placement started with a case series by Nevins et al. . In thisThe effect of PDGF on guided bone regeneration procedures has been tested in numerous studies on humans and animals. Simion et al. treated vertical alveolar ridge defects in two patients; one of them received deproteinized bovine bone block infused with rhPDGF-BB, and the other one was treated with deproteinized bovine bone graft embedded in a rhPDGF-BB-socked collagen matrix . Five moNevins et al. used blocks of equine eHAC alone (control) or in combination with rhPDGF-BB (test) for the treatment of bilateral, surgically-created, vertical bone defects in monkeys . Four moHistologic evidence testing the regenerative potential of rhPDGF in sinus augmentation was performed in only one study by Nevins et al. . The stuNo abnormal or unfavorable effects, such as increased inflammation, ankylosis, or tissue overgrowth, have been reported following the use of rhPDGF-BB, even at the tissue and cellular levels under careful microscopic evaluation following nearly 30 years of histologic evaluation in animal models and many different human clinical indications.The osteopromotive effects of rhPDGF are present histologically as early as two weeks following treatment in animal models.The use of rhPDGF has been most thoroughly evaluated in humans histologically in periodontal infrabony and furcation defects. These studies have consistently found that true periodontal regeneration of cementum, PDL, and bone can be achieved using rhPDGF with allograft, xenograft, and, to a lesser extent, beta-TCP. In contrast, open-flap surgical debridement results in a long junctional epithelium.The histologic effects of rhPDGF have also been evaluated in numerous other clinical indications including peri-implant defects, GBR, extraction sockets, and, to a lesser extent, sinus grafts. In all cases, there was either a statistical improvement in bone regeneration (mostly) or a strong trend towards more bone in rhPDGF-treated sites. Such consistency of observations, despite the differences that might be expected across investigators, indications, models, and surgical techniques, etc., is striking.The use of collagen membranes is contra-indicated when using rhPDGF in intrabony defects and other sites where graft containment and stabilization can be achieved without the use of membranes. If a membrane is indicated for graft containment or stabilization, one should consider a membrane that is not cell occlusive (such as perforated PTFE) when using rhPDGF.Histologic evaluation of biopsies remains one of the most sensitive techniques with which to assess tissue and cellular responses to treatment. Simply stated, histologic evaluation can evaluate responses to therapies, especially growth factors, and either positive or negative reactions that cannot be determined using radiographic or clinical assessments. Therefore, the authors sought to systematically review the histologic response to rhPDGF-BB to determine whether any adverse reactions to its use had been noted on a microscopic level, and whether it appeared to improve tissue regeneration as evaluated histologically in many different clinical indications. Several conclusions can be drawn from this review of histologic studies on rhPDGF-BB:


Endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy (EST) has been proven efficacious in the removal of CBD stones. Even after endoscopic stone removal, recurring cholangitis due to a residual common bile duct (CBD) stone is prevalent in clinical practice with a residual recurrence rate of 4-24% after successful stone retrieval. This comprehensive study and meta-analysis aimed to determine if preventive saline irrigation of the bile duct (PSIB) reduces the amount of residual CBD stones. Through a comprehensive search of PubMed, EMBASE, Cochrane Library, and Web of Science until November 20, 2022, we identified 164 articles comparing the efficacy of PSIB and non-PSIB post-endoscopic CBD stone removal. After stringent selection, three studies were included for meta-analysis using ReviewManager . Using a random effect (RE) model, we derived a pooled odds ratio (OR) with confidence interval (CI) (95%CI). A total of three studies have been included in the analysis. Out of which, two are randomized controlled trials (RCTs) and one is a non-randomized study. Out of 323 patients, 157 underwent PSIB after an endoscopic stone removal of CBD stones to reduce the residual of CBD stones, whereas 166 did not undergo saline irrigation (non-PSIB). In our analysis, PSIB significantly reduced the risk of residual stones . However, there was no notable link between PSIB and post-irrigation cholangitis . Although not statistically significant, PSIB showed a trend toward lowered risks of post-procedural pancreatitis (OR: 0.65), bleeding (OR: 0.68), and other complications (OR: 0.64). PSIB effectively reduces residual CBD stones after endoscopy, offering a cost-effective alternative to invasive procedures such as intraductal ultrasound (IDUS). However, larger RCTs are needed to validate its definitive role. One of the most common gastrointestinal illnesses is cholelithiasis. According to a national survey conducted in Japan, 25.6% of cholelithiasis patients had common bile duct (CBD) stones, which frequently result in serious side effects, such as acute cholangitis, obstructive jaundice, and acute pancreatitis -3. ResidPreventive saline irrigation of the bile duct (PSIB) is a procedure that involves the use of saline solution to flush out the bile duct and remove any remaining stones. It can be performed either percutaneously or endoscopically, depending on the location and size of the stones . This siPreventive saline irrigation usually involves flushing approximately 100 mL of normal saline and aspirated until a clear effluent is seen. Overall, PSIB appears to be a promising approach for reducing the rate of RCBDS and improving patient outcomes following cholecystectomy . EndoscoMethodsWe performed this trial-level meta-analysis according to the Cochrane Collaboration guidelines and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) ,13 .The pre-specified inclusion criteria were as follows: 1) randomized controlled trials (RCTs) and non-randomized studies (NRSs) comparing the outcomes of preventive saline irrigation in the development of bile duct stones after ERCP and (2) studies that report the outcomes of interest. We excluded case reports, case series, animal studies, systematic reviews, meta-analyses, and articles in foreign languages. Duplicates were eliminated, and the remaining articles underwent screening first at the title and abstract levels and subsequently at the full-text level . The process included abstracting information related to trial and participant characteristics, such as age, gender, comorbidities, follow-up duration, inclusion/exclusion criteria, and the definition of primary endpoints. Additionally, the reviewers extracted data on the number of events and sample sizes. Any disagreements or inconsistencies were addressed through discussions or by referring to the original publications.RoB-2 and ROBINS-I were employed for the risk of bias assessment of included studies Figures . We evalOutcomes of interestWe primarily focused on residual CBD stones after endoscopic extraction of stones and post-procedural complications, such as post-procedure cholangitis, post-procedure pancreatitis, post-procedural bleeding, or any other complications.Statistical analysis2 statistic to detect the presence of heterogeneity and quantify it, respectively. The I2 values were interpreted according to the Cochrane Handbook for Systematic Reviews of Interventions, and p < 0.10 was considered statistically significant for the chi-square test. For the primary outcome, we also conducted a sensitivity analysis by excluding NRSs with some concerns of bias due to the non-randomization process. A subgroup analysis based on the study design for the primary outcome was also performed.Meta-analysis was performed via ReviewManager . A Mantel-Haenszel random effect (RE) model was used to calculate the odds ratio (OR) with 95% confidence intervals (CIs). Funnel plots and Egger’s test were used to evaluate for publication bias. Additionally, we performed the chi-square test and IResults2=0%) . However, the pooled analysis of post-irrigation cholangitis demonstrated no significant association with either PSIB or non-PSIB   Figure . The sub) Figure . Though ) Figure  with PSIDiscussionThis meta-analysis of two RCTs and one NRS consisting of 323 patients found that there is a decreased risk of the presence of residual bile stones in patients who went through PSIB after endoscopic stone removal of CBD as compared to the non-PSIB group. However, post-procedural complications, such as pancreatitis, bleeding, and any other complications, were not significantly associated with either group. Additionally, neither the PSIB group nor the non-PSIB group was found to be associated with post-irrigation cholangitis and post-procedural bleeding. There was an individualized decision regarding post-procedural cholangitis, which was specific to certain institutions’ policies.Residual bile duct stones after ERCP have been reported to cause complications such as acute cholangitis . AdditioThe technique of using preventive saline for irrigation varied from one trial to another. For example, 100 mL of saline solution was injected through the catheter from the CBD and aspirated. When the retained stones or sludge were seen at this time, PSIB was performed again until a clear effluent was seen. A side-viewing duodenoscope  was used. Stones were extracted using a basket and/or retrieval balloon, and mechanical lithotripsy was employed if necessary. In another study, a standard duodenoscope  by Olympus was used. Biliary cannulation was attempted, and if difficult, alternative techniques such as precut sphincterotomy were used. Endoscopic sphincterotomy (EST) was performed, usually major EST, but limited EST was used in certain cases. Post-sphincterotomy balloon irrigation is done with 100 mL of sterile saline solution ,14.The proposed mechanism behind CDB stone recurrence involves the fragments of residual stones serving as a nidus for further CBD stone growth ,18. The In this review, PSIB has been associated with a statistically significant reduced incidence of residual bile duct stones without IDUS. This is consistent with findings from a similar study employing saline irrigation but using IDUS to detect residual stones . PublishAmong the included studies, in Jang et al. , endoscoTo the best of our knowledge, this is the first meta-analysis to evaluate the role of PSIB in reducing the rate of residual bile stones after ERCP. The broad inclusion criteria enabled us to include NRSs in addition to RTCs and a better investigation of heterogeneity. The inclusion of studies from diverse settings, populations, and countries also adds to the strengths of this study.One of the limitations of this meta-analysis is that two of the included studies used a follow-up of “six months” to define the presence of “residual stones” as it was difficult to confirm the presence of residual stones without IDUS ,13, and,PSIB was associated with reduced residual CBD stones after endoscopic removal of stones. Additionally, there was no significant association with the risk of post-procedural complications, such as pancreatitis, bleeding, and other complications. The use of PSIB or non-PSIB did not influence the development of post-procedural cholangitis. Current methods for addressing this issue involve additional invasive procedures, such as the placement of naso-biliary catheters or IDUS, which can be uncomfortable for patients and costly. The findings of this review suggest that PSIB, without the need for IDUS, can serve as a feasible and effective alternative for reducing the occurrence of residual stone fragments and, consequently, preventing cholangitis recurrence. Future research, ideally in the form of multi-center RCTs with a larger sample size, is needed to further validate the role of PSIB in reducing the risk of residual CBD stones conclusively.


Pancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods.Based on datasets from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), platelet-related genes were screened out, and the TCGA cohort (n = 171) was identified into two subtypes by unsupervised clustering. The platelet-related risk score model (PLRScore) was constructed by univariate Cox and LASSO regression, and the predictive ability was evaluated by Kaplan-Meier test and time-dependent receiver operating characteristic (ROC) curves. The results were validated in two other external validation sets, ICGC-CA (n = 140) and GSE62452 (n = 66). Furthermore, predictive nomogram containing clinical characteristics and PLRScore was established. In addition, we determined the possible correlation between PLRScore and immune infiltration and response of immunotherapy. Finally, we analyzed the heterogeneity of our signature in various types of cells using single-cell analysis.p < 0.05) were identified. PLRScore model based on four-gene signature  was constructed to predict patient prognosis. The AUCs of training cohort were 0.697, 0.687 and 0.675 for 1-, 3-and 5-year, respectively. Further evaluation of the validation cohorts yielded similar results. In addition, PLRScore was associated with immune cell infiltration and immune checkpoint expression, and had promising ability to predict response to immunotherapy of PDAC.Platelet-related subtypes that have significant difference of overall survival and immune states (In this study, the platelet-related subtypes were identified and the four-gene signature was constructed and validated. It may provide new insights into the therapeutic decision-making and molecular targets of PDAC. Pancreatic adenocarcinoma (PDAC) is one of the malignant tumors with high morbidity and mortality . ExtensiThe experimental evidences showed that platelets not only inhibit blood loss and promote wound healing, but also play an active role in tumor growth, tumor cell extravasation and tumor metastasis . PlateleIn conclusion, platelets are closely related to the growth and progression of cancer. In this study, platelet-related genes were collected and characterized by multi-omics analysis. Then we identified the platelet-related subtypes in PDAC and analyzed the biological characteristics of the subtypes. Then we screened the prognostic factors to construct a prognostic risk model that could differentiate the prognosis of PDAC. Furthermore, the correlation between risk score and clinical features or immune infiltration of PDAC was analyzed.A schematic presentation of the research procedure is shown in Fig. https://gtexportal.org/) and Gene Expression Omnibus  dataset GSE160252 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE160252). The RNA-seq raw read count, fragments per kilobase million (FPKM) and the related clinical information from patients with PDAC were extracted from The Cancer Genome Atlas  database which were used for the construction of our signature. Only samples with survival information were screened for follow-up analysis . For validation of the prognostic model, the clinical follow-up and gene expression were obtained from GSE62452  and International Cancer Genome Consortium . In addition, the Expression profiling and therapeutic information of GSE78220 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE78220) was downloaded for use in immunotherapy-related analysis.To identify the platelet related genes, the gene expression data were downloaded from The Genotype-Tissue Expression  according to the GSE160252, and 1459 genes were obtained. Then, based on the differential expression genes between PDAC and normal pancreatic tissue, 573 differential platelet-related genes (PRGs) were selected from 1,459 genes using DEseq2 package ). The PRGs in the study were performed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway [The differentially expressed platelet-associated genes were selected ( pathway  enrichmeUsing the ‘Non-negative matrix factorization (NMF)’ R package (rank = 2: 6), patients were consensus clustered into two subtypes based on PRGs, and the Kaplan-Meier (K-M) method with log-rank test was performed to compare overall survival (OS) differences between the subgroups. In order to study the differences between two subtypes in platelet-related pathways, gene set variation analysis (GSVA) algorithm was used to analyze the angiogenesis and epithelial to mesenchymal transition (EMT)-related pathway scores. To analyze the differences of immune infiltration status between the two subtypes, CIBERSORT and ESTIMATE algorithms were carried out using R. Then, immune profile differences between subtypes were estimated by Wilcoxon test.p < 0.05 in the univariate Cox analysis, a least absolute shrinkage and selection operator (LASSO) regression model was constructed by “glmnet” package. Finally, the hazard ratios (HR) and regression coefficients for each gene used in the construction of the final prognostic signature. The risk score was calculated using the following formula:Firstly, the PRGs were tested using the univariate Cox analysis to determine the prognostic value. Subsequently, based on the candidate genes with k is the expression of the kth selected gene, and coefk is its regression coefficient. The survival analysis was implemented to compare the OS of the two subgroups. The time-dependent receiver operating characteristic (ROC) analysis at 1, 3, and 5 years of prognostic value was used to assess discrimination of the model in predicting OS of PDAC using the R package ‘survivalROC’. External validation was conducted in ICGA-CA and GSE62452 cohorts, respectively.where e refers to the natural constant, expressionTo assess whether the risk score was able to combined with clinical factors as an independent prognostic factor, uni- and multi-Cox regressions were used to verify the prognostic role of them. Then, a nomogram was established using R package ‘rms’ based on risk score and clinical factors. The predictive effect of the nomogram was validated by ROC and calibration curve.CIBERSORT algorithm and single sample gene set enrichment analysis (ssGSEA) was applied in analyzing the differences of immune infiltration status between high- and low-risk groups. The boxplot was also used to show the difference in the expression of immune checkpoint between high- and low-risk groups.https://ngdc.cncb.ac.cn/gsa/browse/CRA001160) database. To demonstrate the heterogeneity of our signature in the single-cell dimension, the expression of platelet-related signature in each cell was calculated and compared among different cell types. ‘Seurat’ R package was used to generate t-distributed Stochastic Neighbor Embedding (t-SNE) plot for cell type visualization. Comparisons among all cell types were conducted through Kruskal-Wallis test.Expression matrix for single cell transcriptome analysis and clinical characteristics of PDAC were obtained from CRA001160 in the Genome Sequence Archive . A difference of 1459 platelet-associated factors were obtained from the GSE160252 dataset, and 573 PRGs were selected by differential analysis between PDAC and normal tissues. The results were visualized by volcano plot .In order to reveal the heterogeneity of platelet-related genes in PDAC, 171 patients were divided into two subtypes according to the expression profile of PRGs Fig. A. And thPlatelet-related subtypes could distinguish patients with different prognosis, but the number of genes is too large for clinical application. To build a simple scoring model, univariate Cox regression showed that 112 PRGs were potential prognostic factors, and the results were partly shown by forest plot Fig. A. And thp < 0.05). The AUCs of the PLRScore at 1, 3 and 5 years in the GEO cohort were 0.649, 0.762 and 0.775  and PLRScore-low (n = 86). The increased PLRScore was accompanied by gradually decreasing survival time and increased mortality , iDCs, pDSs, Tfh and Th1 cells  was considered essential for cell cycle processes, and there were increasing evidences that up-regulation of CEP55 was involved in the development and progression of various malignancies, including liver cancer , bladderImmune checkpoint inhibitors, targeting CTLA-4 and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in malignant tumors . CTLA4 hOur study had the following limitations: First of all, although we combined bulk and single-cell sequencing data to establish and validate our model, further in vivo and in vitro mechanism exploration may still provide additional information and validation of platelet-related markers for improved treatment strategy in PDAC. Second, the sample size of the external independent immunotherapy cohort we applied was too small, and further clinical trials are also entailed. Finally, we merely discussed the role of platelet in a transcriptomic aspect, the epigenetic process of platelets which is essential in cardiovascular research , and theThis study identified a new platelet-related classification of PDAC, and constructed a risk score model, PLRScore. Our platelet-related subtypes provided insights into the mechanisms associated with immunosuppression and poor prognosis in PDAC. This study described heterogeneity in PLRScore at bulk and single-cell transcriptomic levels. Our four-gene signature, particularly those that have not been studied in PDAC, may provide new insights into the development of more effective biomarkers to predict prognosis and immunotherapy response in patients with PDAC.


We evaluated a decision algorithm for percutaneous coronary interventions (PCI) based on a no-stent strategy, corresponding to a combination of scoring balloon angioplasty (SCBA) and drug-coated balloon (DCB), as a first line approach. Stents were used only in unstable patients, or in case of mandatory bailout stenting (BO-stent).From April 2019 to March 2020, 984 consecutive patients, including 1922 lesions, underwent PCI. The 12-month primary end-point was a composite of major adverse cardiac events (MACE) defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke, and target lesion revascularization. Patients were classified into conventional or no-stent strategy groups according to the PCI strategy. In the no-stent strategy group, they were further classified into BO-stent or DCB-only groups. Their metal index was calculated by stent length divided by the total lesion length.The no-stent strategy was applied in 85% of the patients, and it was successful for 65% of them. MACE occurred in 7.1% of the study population, including 4.2% of all-cause death. Target lesion revascularization was required in 1.4%, 3.6%, and 1.5% of patients in the conventional DES, BO-stent, and DCB-only groups, respectively. MACE occurred more often in the elderly and in those treated with at least one stent .The no-stent strategy, i.e., revascularization of coronary lesions by SCBA followed by DCB and with DES bailout stenting, was effective and safe at 1 year. This PCI approach was applicable on a daily practice in our cath lab.This study was registered with clinicaltrials.gov .Feasibility, safety and efficacy of percutaneous coronary interventions following a decision tree proposing a no-stent strategy in stable patients with coronary artery disease. DES: drug eluting stent; SCBA: scoring balloon angioplasty; BO-stent: at least one stent; DCB: drug coated balloon; BMS: bare metal stent; Bailout (dash lines); MACE: major adverse cardiac event In 1977, Grüntzig started the non-surgical treatment of coronary artery disease, with balloon angioplasty [To overcome these complications, coronary angioplasty and stent insertion began in the 1990s with bare-metal stents (BMS). To reduce in-stent restenosis, first-generation and second-generation drug-eluting stents (DES) have been used since the 2000s. Stenting is currently the first-line treatment for all types of lesions in patients. The disadvantage of DES is that it causes stent thrombosis, which increases the ischemic risk in patients [Drug-coated balloon (DCB) technology led to a 2014 ESC 1A recommendation for the treatment of in-stent restenosis . Since DWe have implemented a decision algorithm for percutaneous coronary intervention (PCI) leading to conventional DES or a no-stent strategy with stenting as a safeguard in case of mandatory bailout (BO). In this single-centre prospective study, we aimed at evaluating the safety and efficacy of this decision algorithm using a 1-year composite clinical endpoint of major adverse cardiac events (MACE), consisting of all-cause death, non-fatal myocardial infarction, non-fatal stroke and target vessel revascularization.Prospective, single-centre study of safety and efficacy of percutaneous coronary intervention.The interventional cardiology unit of a public hospital was staffed with five interventional cardiologists of different levels of experience  in coronary angioplasty and stenting.All consecutive patients in whom coronary angioplasty was performed, i.e., acute coronary syndrome non-ST myocardial infarction (NSTEMI) or ST myocardial infarction (STEMI), chronic coronary syndrome including angina, silent ischemia, ischemic heart disease, were eligible to be included in this study. The exclusion criteria were patients < 18 years of age, pregnancy, legally protected patients or deprived of liberty, and refusal to participate.If the patient was hemodynamically or rhythmically unstable, conventional DES (C-DES) angioplasty was performed. Unstable patients were those in shock, with ventricular hyperexcitability , or at risk of instability if the no-stent strategy were used with prolonged inflation of DCB . The available DES were the Xience , Synergy , and Onyx .In patients eligible for a no-stent strategy, lesion preparation was done with scoring balloons  angioplasty (SCBA). In situations of persistent residual stenosis ≥ 30%, or the occurrence of a dissection at high risk of acute occlusion  could be performed before SCBA.- In case of bifurcation lesion of Medina type 011 or 111, the scoring was done first in the main branch and then in the side branch. After lesion preparation, DCB were first used in the side branch and then in the main branch. In the other types of Medina, bifurcation lesions were treated in the same way as de novo lesions.- In acute thrombotic occlusion (STEMI) with a high thrombus burden, a Minimalist Immediate Mechanical Intervention (MIMI) attitude was advocated before the no-stent strategy, because inflation of the scoring balloon would present a risk of distal thrombus embolization, and a high thrombus burden would significantly reduce DCB drug delivery.The primary end-point was a composite of MACE within 12 months of the procedure. MACE were defined as all-cause death, nonfatal myocardial infarction, nonfatal stroke, and target lesion revascularization.Clinical and procedural data were retrieved from CardioReport™ software (MediReport). Follow-up data were obtained by phone, consultation, or hospital admission. Angiographic variables were calculated as follows. The total length of lesions treated (TLL) is the total length of DES and DCB used per patient. The mean diameter is the sum of the diameter of each material multiplied by its length, and the whole divided by the TLL. The metal index is the total length treated with a DES (or in very scarce cases with a BMS in first line) divided by the TLL. The data underlying this article are available in Zenodo .T test or Kruskal–Wallis or Mann–Whitney tests were used to compare continuous data of independent samples where appropriate. Chi-square or Fisher test of homogeneity was used for categorical variables. An alpha level of 0.05 was used for all statistical tests. Risk factors for MACE were first analysed by bivariate analysis, then a selection of predictors were added in a logistic regression model.Means ± standard deviations or median and interquartile range, counts and percentages were used to describe continuous and categorical variables, respectively. Normal distributions were verified and From April 2019 to March 2020, 984 consecutive patients, totalizing 1922 lesions, underwent interventional revascularization performed during 1136 PCI. One patient declined to participate.Fifteen percent of patients where unstable and required conventional DES, while 85% of the study population was eligible for a no-stent strategy Fig. . RevascuThree-quarters of the patients were male, and the mean age was 69 ± 12 years. Clinical characteristics and cardiology history were similar in patients in the conventional DES, BO-stent, or DCB-only groups, with the exception of family history of coronary artery disease, tobacco use, and clinical presentation , these lesions were successfully revascularised with a no-stent strategy.DCB-only strategy had similar procedure times and contrast volumes as conventional DES strategy Table . BO-stenOf the 1916 lesions, 33% were treated with DES and 67% with DCB  was initiated with a prescription for at least 1 month. Ongoing treatment data were available for 868 patients (88%) at 1 year Table . The majDuring the 1-year follow-up, MACE occurred in 7.1% of the study population Table . Death fThis study reports the 1-year clinical outcomes at a high-volume interventional cardiology centre following the intention to treat PCI patients without permanent implants. The 1-year MACE rate was 7.1%, mainly related to all-cause death (4.2%), with the target lesion revascularization rate remaining low at 2.1%, and the rate of non-fatal stroke and infarction being rare .Our decision tree mostly follows the recommendations of the third report of the international DCB consensus group . The onl. for patient treated with DES [Among patients discharged alive, the 1-year mortality rates in the conventional DES, BO-stent and DCB-only groups were 4.3%, 3.2%, and 1.5%, respectively. This is higher than the 1.5% all-cause deaths reported by Maupas et alwith DES  but conswith DES , 13. In with DES . Schellewith DES , and thewith DES , 13, 15.with DES .Ideally, we would have preferred to study lesion by lesion rather than create a BO-stent group but the clinical analyses would have been impossible. The BO-stent group is typically excluded from studies and may represent one-third of the patients . It inclIn the no-stent strategy group, the procedures included a first step of lesion preparation with balloon scoring. As shown in the PASSWORD study, the systematic use of a scoring balloon seems to guarantee the success of the intervention, whose good outcome is maintained over time . Type A ., [With the exception of unstable patients or those at risk of being unstable, the no-stent strategy was applied to all lesions, including complex lesions . Classical treatments of bifurcation lesions are based on the use of one or two stent with several revascularization techniques . In our ., , which s., , but in ., .. showed an association between total stent length and increased risk of annual MACE [The metal index used in this study allowed classification of patients treated only with DES , those treated with DCB-only , and patients treated with both BO-DES and DCB (BO-stent) who are characterized by an intermediate metal index. From our results, the metal index could be used as a predictor of two events, each with a different time horizon. The first event was early, causal, and patient-related. In-hospital mortality was higher in patients with the highest metal index, as the most severe patients were treated with DES. The second event was later, consecutive, and concerns the ischemic consequences of a potential stent thrombosis. Moving towards the idea of a metal index and its long-term effect, Ejiri et alual MACE .For equivalent procedure duration and total length of lesions treated, the dose-area product was low in the no-stent strategy group. Compared with procedures with DES, the radiation dose required during full stenting optimization, including the complex procedures used to treat bifurcations, such as POT, rePOT, kissing, DK crush, and stent boost, was not necessary once DCB angioplasty was done.At 1 year, the majority of patients treated for chronic coronary syndrome with DCB-only were on SAPT without excess risk of MACE. The no-stent strategy may become a preferential method of angioplasty depending on the patient’s clinical situation and lesion type. It would primarily benefit high-risk ischemic patients, such as young patients by avoiding the cumulative annual risk of very late stent thrombosis, and high-risk bleeding patients, such as elderly or patients on oral anticoagulant for easier management of bleeding risk using a short DAPT or a SAPT.MACE at 1 year does not take into consideration the ischemic risk related to very late stent thrombosis, whose cumulative rate is 0.2–1% per year , 25. TheWe believe that improving the efficacy and safety of the no-stent strategy could be achieved in two key steps. (1) The observed BO-DES rate of around 24% could be improved. For example, intravascular lithotripsy (shock wave) may help in the treatment of severely calcified lesions in coronary vessels and limit the rate of dissection . (2) AltFor stable patients, the no-stent strategy, i.e., revascularization of coronary lesions by scoring balloons followed by DCB, with DES stenting in bailout, is an effective strategy with a low 1-year MACE rate. It has been applicable to the majority of patients’ lesions, including complex lesions such as bifurcations and heavily calcified lesions. This strategy is not time-consuming and is associated with a low radiation dose.