Pancreatic endocrine insufficiency is more likely to occur after acute pancreatitis (AP), but the risk factors affecting pancreatic endocrine function remain controversial. Therefore, exploring the incidence and risk factors of fasting hyperglycaemia following first-attack AP is important.Data were collected from 311 individuals with first-attack AP without previous diabetes mellitus (DM) or impaired fasting glucose (IFG) history treated in the Renmin Hospital of Wuhan University. Relevant statistical tests were performed. A two-sided p-value < 0.05 was considered statistically significant.2 = 6.27, P = 0.012), aetiology , serum total cholesterol (TC) , and serum triglyceride (TG)  were significantly different between the hyperglycaemia and non-hyperglycaemia groups (P < 0.05). The serum calcium concentration  was significantly different between the two groups (P < 0.05). Multiple logistic regression analysis showed that age- ≥60 years  and TG ≥ 5.65 mmol/L  were independent risk factors for fasting hyperglycaemia in individuals with first-attack AP (P < 0.05).The incidence of fasting hyperglycaemia in individuals with first-attack AP was 45.3%. Univariate analysis showed that age (χOld age, serum triglycerides, serum total cholesterol, hypocalcaemia, and aetiology are associated with fasting hyperglycaemia following first-attack AP. Age ≥ 60 years and TG ≥ 5.65 mmol/L are independent risk factors for fasting hyperglycaemia following first-attack AP.The online version contains supplementary material available at 10.1186/s12876-023-02775-7. Acute pancreatitis (AP) is among the most common clinical digestive system diseases. It is an inflammatory disease caused by the abnormal activation of pancreatic enzymes, leading to the digestion of pancreatic tissues. AP has a rapid onset and progression and can develop into moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP), which has many complications, dangerous conditions, and high mortality , 2.The pancreas, which is an important organ of internal and external secretion, plays an important role in digestion and blood glucose regulation. The main cell components of the endocrine pancreas include β-cells that secrete insulin. It has been reported that 37% of patients develop impaired glucose metabolism two years following the first acute alcoholic pancreatitis [Diabetes mellitus (DM) is a universal chronic endocrine disease characterised by elevated blood glucose levels and is anClinical data of 311 individuals with AP hospitalised in the Department of Pancreatic Surgery, Renmin Hospital of Wuhan University, from January 2018 to November 2019, were retrospectively collected. All procedures were conducted in accordance with the relevant guidelines and regulations. Patients who met the inclusion and exclusion criteria were included in the analysis. The time from onset to admission was no more than 7 days.This study was conducted in accordance with the principles of the Helsinki Declaration. Due to the retrospective characteristics of the study from January 2018 to November 2019, informed consent was waived and the study was approved by the ethics committee of the Renmin Hospital of Wuhan University (Registration Number: WDRY 2020-K177).Those who met any two of the following three criteria were considered to have been diagnosed with AP: (1) abdominal pain consistent with AP; (2) serum amylase or lipase activity three times higher than the normal upper limit; and abdominal imaging examination consistent with AP imaging changes. (3) IFG and DM diagnosed according to the World Health Organization (WHO) criteria  .The clinical data collected included the following: sex, age, cause of AP, grades of severity, hospital inspection results in 48 h , serum triglyceride (TG), serum albumin (ALB), white blood cell (WBC) count, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum levels of total bilirubin (TBIL), direct bilirubin (DBIL), urea, creatinine, and serum Ca9 /L was used as the boundary. (7) According to WHO diagnostic criteria for DM [(1) According to the Atlanta AP diagnostic criteria , individa for DM , individFPG was detected using glucose oxidase. 3.0 ml of elbow venous blood was collected from all individuals with AP 12 h after fasting. A Siemens ADVIA® XPT automatic biochemical analyser and supporting reagents were used for detection. The average FPG values of the last two measurements (the day of and the day before discharge) were statistically analysed.2 test). The distribution characteristics of the measurement data were tested using the Shapiro-Wilk method. The Mann–Whitney U test was used for skewness distribution data, which were represented by the median and interquartile range (IQR). Multiple imputations were performed by using 20 iterations to assure convergence for missing values (Supplementary Table 1). Statistically significant variables were included in the multivariate binary logistic regression analysis, and a stepwise regression method was used. All statistical tests were two-sided, and a p-value < 0.05 was considered statistically significant.SPSS 22.0 statistical software was used for analysis. The counting data were represented by the number of cases and percentage  and were compared using a single factor analysis  age of 52 years (IQR: 38–64 years). MAP, MSAP, and SAP accounted for 80.4, 6.4, and 13.2%, respectively. The proportion of biliary AP was significantly higher than that of hyperlipidaemic and other etiological groups. The cause of AP includes alcohol consumption, pregnancy, trauma, and endoscopic retrograde cholangiopancreatography. After the initial onset of AP, the proportion of individuals in the hyperglycaemia group was 45.3%, of which IFG accounted for 16% and DM 29.3% . The incidence of hyperglycaemia in the hyperlipidaemia group was significantly higher than that in the biliary and other etiological groups . The incidence of fasting hyperglycaemia was higher when TC was ≥ 6.21 mmol/L or serum TG was ≥ 5.65 mmol/L . That is, age, aetiology, TC, and TG levels were correlated with fasting hyperglycaemia in people after a first-attack AP (Table The results showed that fasting hyperglycaemia occurred more frequently in people aged ≥ 60 years (χ2+) were analysed using the Shapiro-Wilk test, and the above data were skewed distribution measurements. The results showed no significant differences between the discharged fasting hyperglycaemia and control groups (P > 0.05). Only the serum Ca2+ concentration showed a statistically significant difference between the two groups (P < 0.05)  Table . That isP < 0.05), compared with individuals with aged < 60 years, the possibility of fasting hyperglycaemia after first-attack AP was 2.631 times. TG ≥ 5.65 mmol/L  was an independent risk factor for fasting hyperglycaemia (FPG ≥ 6.1 mmol/ L) in first episode of AP individuals (P < 0.05), compared with individuals with TG < 5.65 mmol/L, the possibility of fasting hyperglycaemia was 3.964 times  was an independent risk factor for fasting hyperglycaemia (FPG ≥ 6.1 mmol/ L) . However, one-fifth of patients’ conditions will progress to severe disease, with a mortality rate of approximately 20% . HyperglPancreatic endocrine function injury after AP has gradually attracted attention. Petrov et al. found that islet cell damage and insulin resistance are important causes of hyperglycaemia in people with AP . PatientCurrent studies suggest that IFG or IGT after diabetes and AP is related to age . Some stSex is not a reported factor influencing IFG or DM after AP , 31, whiBiliary tract disease, hyperlipidaemia, and excessive alcohol consumption are three important factors associated with the occurrence of AP . AdditioThe severity of AP depends on the extent of the local injury in and around the pancreas, as well as systemic injury to remote organs. The proportion of patients with different severity of AP varies across different studies. Population-based studies have shown the proportion of SAP between 8% and 20% . MoreoveSome studies have reported that AP severity is not associated with emerging diabetes , 30, whe2+ promotes excessive activation of trypsinogen, leading to digestive injury of the pancreas [2+ influx occurs in the AP, and increased intracellular Ca2+ concentration leads to decreased blood Ca2+ concentration and intracellular ATP depletion [During AP, the abnormal accumulation of intracellular Capancreas . Ca2+ inepletion . After tepletion . Our resThe effect of renal function indices on fasting hyperglycaemia in individuals with first-attack AP has rarely been reported. Renal insufficiency and dysfunction are common in AP, especially in individuals with SAP. During SAP, a large amount of fluid flows into the third space, resulting in decreased renal blood perfusion. Renal tubules may be damaged due to blood hypercoagulability and infection, resulting in renal insufficiency or dysfunction . This stThis was a retrospective study; MAP accounted for a large proportion, and the number of individuals with MSAP and SAP was insufficient. Because of the limited number of cases, our descriptions of the AP aetiological and leukocyte classifications are insufficient; therefore, more cases are needed to refine related classifications and conduct in-depth research. It is too simple to classify the age groups based on clinical experience. Age-based differences in the incidence of hyperglycaemia should be carefully distinguished. Our results suggest age and triglyceride have important effects on AP after fasting blood glucose. More samples in multi-centre prospective clinical studies are required for a more detailed testing index and classification of variables for revealing the incipient AP fasting hyperglycaemia in individuals with mechanisms and identifying more influence factors to resolve.Fasting hyperglycaemia (FPG ≥ 6.1 mmol/L) occurred in 45.3% of the individuals with first-attack AP after treatment. Age ≥ 60 years and TG ≥ 5.65 mmol/L were independent risk factors for fasting hyperglycaemia in individuals with first episode of AP. In clinical practice, the occurrence of fasting hyperglycaemia after AP should be considered for people with first episode of AP with no history of IFG or DM, age ≥ 60 years, and TG ≥ 5.65 mmol/L. Clinicians should alert individuals with elevated blood glucose levels and strengthen blood glucose monitoring and management during hospitalisation and early intervention. Concurrently, blood glucose monitoring should be continued after discharge and interventions should be administered in advance for people with pre-DM through dietary regulation and oral hypoglycaemic drug treatment to prevent and cure IFG or DM after AP.Below is the link to the electronic supplementary material.Supplementary Material 1


An increasing number of robotic pancreatoduodenectomies (RPD) are reported, however, questions remain on the number of procedures needed for gaining technical proficiency in RPD. Therefore, we aimed to assess the influence of procedure volume on short-term RPD outcomes and assess the learning curve effect.A retrospective review of consecutive RPD cases was undertaken. Non-adjusted cumulative sum (CUSUM) analysis was performed to identify the procedure volume threshold, following which before-threshold and after-threshold outcomes were compared.p < 0.001). No significant difference was found between before- and after-threshold groups in major Clavien-Dindo complications .Since May 2017, 60 patients had undergone an RPD at our institution. The median operative time was 360 min (IQR 302.25–442 min). CUSUM analysis of operative time identified 21 cases as proficiency threshold, indicated by curve inflexion. Median operative time was significantly shorter after the threshold of 21 cases (470 vs 320 min, A decrease in operative time after 21 RPD cases suggests a threshold of technical proficiency potentially associated with an initial adjustment to new instrumentation, port placement and standardisation of operative step sequence. RPD can be safely performed by surgeons with prior laparoscopic surgery experience.The online version contains supplementary material available at 10.1007/s00464-023-09941-8. Pancreatoduodenectomy (PD) remains a mainstay curative approach for head and neck of pancreatic, periampullary and duodenal, and distal bile duct tumours . PancreaThese concerns revolve around the learning curve for new surgical techniques, as it was previously shown in LPD that as many as 104 cases might be needed before expert proficiency . As suchAs such, similar questions are being posed regarding RPD, particularly given the current higher cost of robotic surgery tools. However, robotic surgery may address some of the technical difficulties of LPD, providing 3D vision with increased depth perception, additional degrees of freedom due to ‘endo-wristed’ instruments, standard instruments for robotic operation and eliminating both instrument and camera tremor and variability . Indeed,The learning curve effect has implications not only for trials reporting on RPD but also for future training of hepatopancreatobiliary surgeons. As such, understanding the factors that contribute to the learning effect and identifying the proficiency threshold is paramount to safe and widespread adoption of RPD, as well as assessment of its outcomes. Therefore, we analysed consecutive cases of RPD performed to date at our institution and aimed to assess the influence of procedural volume on short-term RPD morbidity outcomes, and operative variables. Additionally, we aimed at identifying a threshold of proficiency for RPD, expressed as a number of cases needed to overcome the learning curve.A prospectively maintained database of patients who underwent RPD was retrospectively reviewed to include all the cases of RPD between May 2017 (first RPD case) and December 2021 performed at our institution, a hepatopancreatobiliary tertiary referral centre in the United Kingdom. Our institution consists of two pancreatic surgeons who perform sixty pancreatic resections annually . One surgeon performs RPD whenever a robotic theatre is available. Prior to starting RPD this surgeon had performed 100 laparoscopic PD after a 10 year experience with open PD. Consecutive patients undergoing RPD for both malignant and benign pathologies were included in this analysis. RPD was performed with the Da Vinci Si, X and Xi models  by a single senior surgeon (LJR). All patients selected for operative management following a multi-disciplinary discussion were considered for the robotic technique, but those with borderline resectable disease with the potential for venous invasion  or superior mesenteric vein (SMV)) identified on pre-operative imaging were excluded. At the time of this cohort (2017–2021) our institution did not give neoadjuvant chemotherapy (NAC) to patients with upfront resectable pancreatic ductal adenocarcinoma, while from 2020, those with borderline resectable disease were given NAC however these patients, likely to require vascular resection were scheduled for open PD rather than RPD. Cases which were abandoned intraoperatively were removed from the analysis. There was no cutoff with regards to BMI for consideration of robotic technique. The selection criteria for RPD did not change throughout the study period. This research followed the principles outlines in the Declaration of Helsinki, and written consent was sought for patients for inclusion in the database. This study was conducted according to STROBE guidelines .Our robotic technique is adapted from that originally published by Giulianotti et al. and was previously described by our group in detail , 18. In All cases were classified as either low-risk or high-risk based on classification proposed by Sanchez-Velazquez et al.  The risk2 test. The threshold of statistical significance was set at p < 0.05. Data were analysed and presented using R3.6.3 .Continuous data were summarised as median (interquartile range (IQR)) with non-parametric data identified following visual evaluation of the distribution and Shapiro–Wilk assessment for normality. To identify the learning effect and potential proficiency threshold, a cumulative sum (CUSUM) analysis was performed. Due to the single institution character and number of cases included, as well as no formal recording of long-term follow-up, we decided to focus on transition between competence and proficiency stages, whilst the transition from proficiency to mastery stages was outside of the scope of this study . CUSUM cn = 53, 88.3%), while seven (11.7%) were pylorus preserving RPDs.Sixty-five patients underwent a robotic pancreatoduodenectomy between May 2017 and December 2021 at our institution. One patient who has had an additional spleen-preserving total pancreatectomy was excluded from the analysis. Of the 64 cases remaining, four (4.7%) cases were abandoned due to metastatic spread of disease, resulting in 60 RPD cases completed, and included in the final analysis. The majority of were standard robotic pancreatoduodenectomy . The average BMI was 27.2 ± 5.7 kg/m2 (range 18.0–44.0). The median pre-operative ASA grade was 3 (IQR 2–3), and three patients (5.0%) had undergone previous abdominal surgery. None of this RPD cohort received NAC. 24 (40.0%) were classified as low-risk cases, while 36 (60.0%) were classified as high risk cases. According to ISGPS classification, pancreas texture and main pancreatic duct size intraoperative assessment 28.3% (n = 17) of cases were type A, 1.7% (n = 1) type B, 28.3% (n = 17) type C, and 36.7% type D (n = 22). Pancreatic texture data were not available for three cases (5.0%).The median age was 63.5 (range 19–86), and the majority of patients were male (The median operative time was 360 min (IQR 302.25–442 min), while the median robotic console time was 317.5 min (IQR 270–413 min). Two (3.3%) operations required conversion to open. One patient required perioperative transfusion related to intraoperative blood loss (1.7%), with an additional single patient (1.7%) having a clinically significant estimated blood loss of more than 500 ml.n = 15), while 34 patients had at least 1 complication (56.7%). The CR-POPF rate was 0%, with 6 (10.0%) patients developing biochemical leak. The re-operation rate was 6.7% (n = 4), in all cases due to post-operative bleeding, while endoscopic re-intervention occurred in one patient (1.7%) for bleeding gastric ulcer management. Two patients (3.3%) required interventional radiology embolisation for bleeding, while four patients (6.7%) required percutaneous drainage of collections. Delayed gastric emptying rate was 1.7% (n = 1). The overall 90-day mortality rate in the cohort was 1.7% (n = 1); this patient had a myocardial infarction on postoperative day seven.Full post-operative outcomes data are present in Table n = 46, 76.67), with pancreatic ductal adenocarcinoma being the most common tumour type, accounting for a third of all resected tumours . For malignant tumours, the R0 resection rate was 71.2% (n = 33). The median number of lymph nodes (n = 20) retrieved was higher than the 15, recommended by The European Society for Medical Oncology (ESMO) [Histopathological data are summarised in Table y (ESMO) .Table 2Hn = 6) had evidence of disease recurrence within the follow-up period.Long-term follow-up data were available, with a mean follow-up of 8.8 months. During the study period, seven patients have died, resulting in an 88.3% overall survival rate in the cohort and 83.7% overall survival in those with malignant disease. 13.0% of those with a malignant pathology , POPF rate, bile leak rate and re-operation rate, no clear threshold of procedures suggesting proficiency could not be identified Fig. . Multipln = 0) vs 7.7 . A full comparison of baseline characteristics between the subgroups is presented in Supplementary Table 1. The operative time was significantly longer in the competency phase, compared with the proficiency phase . There were no significant differences in morbidity between the two subgroups in terms of all morbidity, major morbidity, biochemical leak and re-operation rates. A full comparison of operative outcomes is presented in Table According to the proficiency threshold identified through operative time CUSUM analysis, the RPD outcomes were divided into the competency phase (cases 1–21) and proficiency phase (cases 22–60), following which the outcomes were compared in two subgroups. The subgroups were comparable in terms of age, sex, % of low-risk patients, % of PDAC patients, ASA grade and BMI, although of note, the competency phase subgroup had significantly no patients with previous abdominal surgery, although the difference was not significant 0% . While the indications for RPD did not change through study period, this being a non-comparative, non-randomised study, selection bias could have influenced the results, and differences between baseline characteristics of subgroups should be explored in more detail in the future to try to identify a subgroup of patients most likely to benefit from RPD.No consensus has been reached about the optimal metric of proficiency , 23. WhiThe decrease in operative time after 21 cases is multifactorial. During the learning phase, prior to a standardised order of steps and technique, frequent changes of instruments and operative steps could have contributed to lengthening the operation. For example, rather than dissecting, clipping or tying and dividing tissues and pedicles individually we have now standardized the procedure to perform all the relevant dissections first in one particular area followed by clipping/tying and division in order to reduce the frequency of instrument changes. Further, the economy of motion, using the camera and three instrument arms, rapidly improves with continued practice. We hypothesise that during the competency phase, lack of standardisation of operative step sequence, combined with adaptation to new instruments and tasks, leads to increased operative time. The prior extensive experience in both open and laparoscopic pancreatic surgery in our centre could also have shortened the learning curve, however, the extent to which proficiently in the same surgical procedure across multiple surgical approaches (open vs laparoscopic vs robotic) is transferable has yet to be studied in detail. It is worth noting, that there was no difference in morbidity and POPF rates, suggesting that despite the existence of a technical proficiency curve, there was no short-term outcome learning curve effect present for RPD in our series . When con = 4, 6.7%) rates were low across the cohort and comparatively lower than the rates reported in the existing literature [The benchmarking for operative variables attests to the robustness of outcomes in our case series. Of note, CR-POPF (0.0%) and re-operation , however, we have found little difference in terms of docking time between Si and X da Vinci with a head-on docking and Xi with side docking for PD, as there was no change in operative field required, hence no redocking intraoperatively which features in robotic colorectal resection. Finally, the senior surgeon (LRJ), who performed all of the RPD in this series, had previous experience in laparoscopic surgery and other robotic hepatopancreatobiliary procedures, including distal pancreatectomy, but had no procedural-specific robotic training or mentorship programme. Such mentorship programmes have been previously shown to the improve learning curve profiles and reduce the number of cases needed for proficiency, potentially allowing surgeons with no extensive prior PD experience to attain proficiency in a similar timeframe . As suchThe existence of the learning phase should have an impact on future clinical trials evaluating RPD against other surgical interventions. One of the early criticisms of minimally invasive PD is that it has higher complication rates and mortality compared with OPD, especially in low volume centres  . EstabliAs such, RPD should remain only confined to specialist centres with hepatopancreatobiliary experience and where a standardised robotic training program has been followed. In this way, RPD is safe to implement, as seen in the Netherlands and in Japan , 31. A tSupplementary file1 (DOCX 14 KB)Below is the link to the electronic supplementary material.


P = 0.002) and matched cohorts . The 5-year OS rate after LT could be improved to 61.7% in patients with local advanced ICC after neoadjuvant chemotherapy. In conclusion, our study demonstrated that the prognosis of patients with ICC after LT was better than patients with ICC after LR, but was still worse than patients with HCC after LT. LT with neoadjuvant chemotherapy should be considered as a treatment option for patients with locally advanced ICC, but more prospective multicenter clinical trials are needed to further confirm these results.Liver resection (LR) is the only recommended effective curative treatment for patients with intrahepatic cholangiocarcinoma (ICC), but the prognosis of patients with ICC is still poor even after curative resection. Recently, many researchers focused on the therapeutic value of LT for patients with ICC. This study aimed to identify the role of liver transplantation in patients with ICC by internally comparing with LR in ICC and externally comparing with LT in HCC. We obtained patient data from SEER database. Propensity score methods were applied to control confounders. Survival outcome was estimated using Kaplan–Meier survival curves and compared using the log-rank test. A total of 2538 patients with ICC after surgery and 5048 patients with HCC after LT between 2000 and 2019 were included in this study. The prognosis of patients with ICC after LT were better than patients with ICC after LR in both unmatched (HR 0.65,  ICC arises from the epithelial layer of the second-degree biliary tract and has a high degree of malignancy5. Liver resection (LR) is the only effective curative treatment option for ICC6. However, even after curative resection, the prognosis of ICC in patients remains poor, with a 5-year overall survival (OS) rate of only 20–35%7.Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer after hepatocellular carcinoma (HCC) with an increasing trend in both global incidence and mortality rate9. The 1-year and 5-year OS rates in patients with HCC after LT exceed 85% and 70%, respectively, in most centers10. Historically, LT has not been recommended for patients with ICC because of improper patient selection and lack of neoadjuvant therapy. However, at present, LT outcomes in patients with ICC have significantly improved due to proper patient selection and application of neoadjuvant therapies12.Liver transplantation (LT), a standard treatment for early-stage HCC, can be used to treat the tumor as well as resolve underlying liver diseases, and it has shown the highest therapeutic value among all treatments available for HCC14, to the best of our knowledge, a consensus for performing LT in patients with ICC has not yet been reached. However, two potential selection criteria have been identified: ①very early stage tumor  with cirrhosis; and ②locally advanced tumor with neoadjuvant chemotherapy15.Therefore, this study aimed to identify the role of LT in patients with ICC by an internal comparison with the role of LR in patients with ICC and an external comparison with the role of LT in patients with HCC.Although the Milan criteria have been used to select patients with HCC to undergo LT worldwideWe analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database, after signing a data agreement ; moreover, our study was exempted from ethical review. This article does not include data obtained from human participants by any of the authors.We obtained patient data from the SEER Research Plus Data, 17 Registries, Nov 2021 Sub (2000–2019) incidence database, using SEER*Stat version 8.4.0. A total of 2538 patients with ICC after curative surgery and 5048 patients with HCC after LT were included in this study. The following variables were used in the analysis: patient age, sex, race, marital status, American Joint Committee on Cancer (AJCC) stage, tumor size, tumor grade, surgical approach, radiotherapy(Y/N), chemotherapy (Y/N), fibrosis score, months of survival, and OS status.2 test performed for continuous and categorical variables, respectively. To control the possible effects of the measured confounders, propensity score methods were applied. The propensity score was calculated using a multivariate logistic regression model, that included patient age, sex, race, marital status, AJCC stage, tumor size, tumor grade, radiotherapy(Y/N), chemotherapy (Y/N) and fibrosis score. Balanced cohorts were created using the one-to-one nearest-neighbor propensity score matching (PSM) method16. Survival was estimated using Kaplan–Meier survival curves and compared using a log-rank test.The baseline characteristics of patients with ICC after LR and LT were compared using the Kruskal–Wallis test and χhttp://www.r-project.org/). Statistical significance was set at p < 0.05.All statistical analyses were performed using SPSS  and R software  and had a male predilection  as compared to those in the LR cohort. The tumor characteristics also differed between the patients in LR and LT cohorts. Patients with an early AJCC stage, small tumor size, well-differentiated tumor grade and cirrhosis were more likely to undergo LT (p < 0.01). After PSM, no significant differences were observed between the patients in LR and LT cohorts. The baseline characteristics of the unmatched and matched cohorts are shown in Table A total of 2538 patients with ICC who underwent curative surgery and 5048 patients with HCC who underwent LT were enrolled in this study. Among the 2538 patients with ICC, most (95.5%) underwent LR, and only 113 (4.5%) underwent LT. Patients with ICC in the LT cohort were younger ] ] : 0.65    + cirrhosis; and criteria 2 as: locally advanced tumor (AJCC stage I and II) + chemotherapy. After selection, 10 patients with ICC undergoing LT met the criteria 1 and 31 patients with ICC undergoing LT met the criteria 2. Survival analyses were performed for the different patient subgroups. The 5-year OS rate for patients undergoing LT who met selection criteria 1 and 2 were 43.8% and 61.7%, respectively (Table p < 0.001)]. The 5-year OS rates in patients with ICC and patients with HCC undergoing LT were 52.8% and 74.9%, respectively ] . The results of our study are encouraging because it is generally accepted in the transplant community that a 5-year OS rate of at least 50–60% is required for a transplant indication to be considered acceptable20.Currently, LR is the only widely accepted curative treatment for ICC. However, the 5-year OS rate in patients with ICC after LR has been reported to be 20–40%15. Our study analyzed the survival outcomes of the selected patients with ICC after LT based on these two criteria. We found that the 5-year OS rate after LT improved to 61.7% in patients with locally advanced ICC after neoadjuvant chemotherapy. However, a 5-year OS rate of 43.8% was observed in patients with very early stage ICC with cirrhosis. This unsatisfactory result could be owing to the relatively small sample size (only 10 patients with ICC had tumor size ≤ 2 cm and cirrhosis).In the recent years, the two potential selection criteria defined for patients with ICC undergoing LT are as follows: ①very early stage tumor  with cirrhosis; and ②locally advanced tumor with neoadjuvant chemotherapy21. Thus, only the survival superiority of LT over LR or a 5-year OS rate of 61.7% did not justify LT indication in patients with ICC. Our study further analyzed the survival outcomes in patients with ICC undergoing LT compared to those in patients with HCC. However, the prognosis of ICC in patients after LT was worse than that of HCC in patients .Regardless of the underlying disease, the goal of LT is to provide liver recipients with the maximum possible benefit from the limited donor liver source22. Lunsford et al. further reported that patients with locally advanced ICC who showed pre-transplant disease stability after neoadjuvant therapy benefited from LT. The 1-year, 3-year and 5-year OS rates were 100%, 83.3% and 83.3% respectively, although it should be noted that the sample size of this study was very small (6 patients with ICC after LT)23. These findings indicate the promising prospects of LT in selected patients with ICC.Notably, the OS in the selected patients with ICC who underwent LT has significantly improved in some centers. Sapisochin et al. reported that patients with cirrhosis and very early-stage ICC (single tumor ≤ 2 cm) had good survival outcomes after LT In conclusion, our study analyzed the survival outcomes in patients with ICC undergoing LT compared to those in patients with ICC after LR and in patients with HCC after LT. Our results demonstrated that patients with ICC after LT had a better prognosis than those after LR and the 5-year OS rate after LT was improved to 61.7% in patients with local advanced ICC after neoadjuvant chemotherapy. However, the prognosis of ICC in patients after LT was worse than that of HCC in patients after LT, which questioned the justification of performing LT in patients with ICC. LT with neoadjuvant chemotherapy should be considered as a treatment option for patients with locally advanced ICC; however, more prospective multicenter clinical trials are needed to confirm these results.Supplementary Table 1.


The purpose of this pilot study was to investigate associations between fibrinogen/fibrin degradation products (FDP) to high density lipoprotein-cholesterol (HDL-C) ratio (FHR) of mothers and the risk of delivering large/small for gestational age (LGA/SGA) infants and to evaluate the predictive power of FHR on LGA/SGA.This study retrospectively reviewed 11,657 consecutive women whose lipid profiles and FDP levels were investigated at the time of admission for delivery at a specialized hospital. The FHR was calculated, and perinatal outcomes, including clinical parameters, were analyzed.P < 0.01) and higher in women who delivered LGA infants  compared with those who delivered infants of normal size for their gestational age. Women in the top quartile for FHR (> 5.9 mg/mmol) had a 2.9-fold higher risk of delivering LGA infants  and a 47% lower risk of delivering SGA infants  than those in the bottom quartile (< 2.7 mg/mmol). In addition, adding FHR to the conventional models significantly improved the area under the curve for the prediction of delivering LGA  and SGA  infants.The prevalence of SGA was 9% (n = 1034), and that of LGA was 15% (n = 1806) in this cohort study. FHR was significantly lower in women who delivered SGA infants (4.0 ± 3.2 vs. 4.7 ± 3.3 mg/mmol, These findings suggest that the FHR calculated in late pregnancy is an innovative predictor of delivering LGA and SGA infants. Combining FHR with perinatal parameters could thus enhance the predictive ability for predicting the delivery of LGA/SGA infants.The online version contains supplementary material available at 10.1186/s12944-023-01986-x. Birth weight is often recognized as an index to evaluate foetal intrauterine growth. Abnormal foetal growth could affect the incidence of diseases in adulthood based on the theory that diseases that occur later on in life originate from when the foetus is in the womb . NewbornFor foetuses to grow properly, there are a variety of maternal biological and physiological changes that must occur during pregnancy. Studies on indices of these modifications are becoming more popular. Until now, a number of factors, such as maternal micronutrients from one-carbon metabolism and glucolipid metabolites and coagulation-related parameters, have been correlated with neonatal birth weight –9. HowevThe exploration of more efficient indicators appears to have important significance not only for foetal birthweight itself but also for the prediction of adverse LGA/SGA. It remains unclear whether a combination of FDP and HDL-C [FDP to HDL-C ratio (FHR)] can be a reliable indicator of LGA/SGA. The assumption of this pilot research was that FHR is more efficient in predicting the delivery of LGA/SGA infants than using either FDP or HDL-C alone. To bridge this knowledge gap, the objective of this pilot study was to comprehensively assess the associations of maternal FHR, FDP, and HDL-C with foetal birthweight and the delivery of LGA/SGA infants among the Chinese population, and to evaluate the power of FHR before delivery to predict the delivery of LGA/SGA infants.From April 2016 to March 2017, an observational study was performed in Changzhou city, eastern China. A total of 13,275 consecutive pregnant women who delivered at Maternal and Child Health Care Hospital of Changzhou were initially included in this retrospective study to explore the associations between antenatal measurements of relative biomarkers and adverse birth outcomes. The inclusion criteria were as follows: (1) pregnancy at 28–41 gestational weeks; (2) singleton pregnancy and live birth; and (3) clearly completed medical records. The exclusion criteria were as follows: (1) use of illicit drugs and alcohol and smoker; (2) major prepregnancy diseases ; (3) foetal congenital malformation; and (4) no results of FDP and HDL-C. A total of 1618 observational subjects were excluded from the present cohort for the following reasons: (1) 335 cases with multiple gestation; (2) 96 cases without live births; (3) 488 cases with pregestational diseases; and (4) 699 cases without FDP and HDL-C measurements . Anonymous data were analysed and written informed consent for observational subjects was waived in the present study.2), overweight (25–29 kg/m2) and normal weight (< 25 kg/m2) according to the World Health Organization classification of BMI [Maternal age was classified as advanced (≥ 35 years) or appropriate (< 35 years) . Pregnann of BMI . The dian of BMI . Accordierweight –29 kg/m2The distributions of continuous variables were investigated by using the Kolmogorov‒Smirnov test. The variables following skewed distributions were described as the median [inter-quartile range (IQR)], and those following normal distributions were expressed as the mean [standard deviation (SD)], and categorical variables were expressed as percentages. To compare the differences in anthropometric and laboratory parameters among the quartiles of maternal FHR, chi-square, Kruskale‒Wallis and ANOVA tests were performed for categorical variables, nonnormally distributed continuous variables and normally distributed continuous variables, respectively. Spearman’s test was applied to determine the correlation of FHR with other indices. The birth weight and length were first treated as continuous variables, and linear analysis models were applied to assess the impacts of different indices  on these variables. When birth weight (LGA and SGA) was defined as a categorical variable, logistic analysis models were applied to investigate associations of LGA/SGA with FHR, FDP, and HDL-C. Adjusted variables included age, BMI, BP, parity, gestational age, pregnancy complications, assisted reproduction, and foetal sex and the levels of total cholesterol, triglycerides, LDL-C and hsCRP. Similarly, odds ratios (ORs) [95% confidence interval (CI)] of FHR on LGA/SGA across each subgroup were calculated, and their interactions were determined. Receiver operating characteristic (ROC) curves were analysed to compare the area under the curve (AUC) calculated by FDP, HDL-C, FHR and models to predict the delivery of SGA and LGA infants. Youden’s index was used to determine the cut-off value to predict the delivery of SGA and LGA infants.P < 0.05 indicated statistical significance.Empower software  was used in all the statistical analyses. A two-tailed 2 and more than 60% of them were nulliparous. The median birth length and weight, and gestational week were 50 cm, 3337 g, and 39 weeks, respectively. Among the 11,657 newborns, 1806 (15%) were classified as LGA, and 1034 (9%) were classified as SGA. Table P < 0.01; Fig. The median age of the participants was 28 years old range 15–47). Approximately 75% of observational subjects had a prenatal BMI ≥ 25 kg/m5–47. Appr = 0.04, P < 0.01), gestational age , triglyceride level , FDP level , and birthweight  and adversely correlated with systolic BP , diastolic BP , hsCRP level , total cholesterol level , and HDL-C level .Table P for trend < 0.01). The risk of delivering a LGA infant showed an increasing trend in association with women with an FHR in the second, third and fourth quartile .The associations of FDP, HDL-C, and FHR with foetal growth, and the delivery of LGA and SGA infants are presented in Table P for the interactions > 0.05). Notably, the incidence of SGA infants delivered by obese pregnant women (BMI ≥ 30 kg/m2) with high FHRs (> 5.9 mg/mmol) was significantly lower than that of SGA infants delivered by normal weight women (BMI < 25 kg/m2) with low FHRs , indicating a 14.8% decrease in absolute risk and an 84% decrease in relative risk . Additionally, the incidence of LGA infants delivered by obese pregnant women with high FHRs was significantly elevated compared with that of LGA infants delivered by obese pregnant women with normal weights and low FHRs (37.0% vs. 5.1%), indicating a 31.9% increase in absolute risk and an 8.8-fold relative risk .In subgroup analyses, the effects of other covariates on the association between FHR (≤ 5.9 vs. >5.9 mg/mmol) and the delivery of LGA/SGA infants were further evaluated. As presented in Tables P < 0.01, Table P < 0.01) and the AUC of SGA from 0.717 to 0.727 (P < 0.01).To determine the cut-off points of FDP, HDL-C, FHR and related models for the prediction of delivering SGA and LGA infants, a ROC analysis was performed Fig. . The AUCIn this pilot study, the maternal FHR index before labour was positively associated with LGA delivery and negatively associated with SGA delivery. The associations between FHR and LGA/SGA risk were markedly enhanced by BMI. In addition, FHR had a significantly higher AUC in predicting the delivery of LGA/SGA infants than FDP and HDL-C. Notably, these findings demonstrated that adding FHR into the traditional models could significantly increase the power of predicting the delivery of SGA and LGA infants.P < 0.01; LGA: adjusted OR = 0.60, P < 0.01; SGA: adjusted OR = 1.15, P = 0.29). Additionally, this study determined the predictive value of HDL-C to the delivery of LGA infants and SGA infants by using ROC analysis and found that the AUC of the optimal cut-point of < 1.73 mmol/L for the delivery of LGA infants is higher than that of the cut-point of > 1.89 mmol/L for the delivery of SGA infants (0.576 vs. 0.544).Maternal TC, TG, and LDL-C levels increase gradually as the pregnancy progresses, reaching a peak in late pregnancy. In contrast, HDL-C concentration increases from early and middle pregnancy with a slight fall in late pregnancy , 27. MatP < 0.01). In addition, ROC analysis suggests that FDP levels have a similar AUC for predicting the delivery of LGA or SGA infants (0.573 vs. 0.577). However, the AUC of the best cut-off values for SGA and LGA infants was relatively poor, suggesting that it is unsatisfactory for predicting these outcomes based on FDP or HDL-C levels alone. Then, FHR was introduced to improve the predictive power. Although FHR had a significantly greater AUC for predicting the delivery of SGA/LGA infants than FDP and HDL-C, the AUC was still unsatisfactory . The feasible predictive models based on prenatal clinical parameters may provide an opportunity to identify women at risk of delivering LGA/SGA infants. This study revealed that FHR, by itself, showed poor power for predicting the delivery of LGA/SGA infants in late pregnancies; however, adding FHR to the models based on prenatal parameters in late pregnancy increased the ability to predict these outcomes . In addition, until s the exact mechanism contributing to the association between the FHR and birth weight remains unclear.It is generally believed that FDP level remains stable throughout pregnancy despite hypercoagulability during pregnancy . HoweverThe strengths of this pilot study included the observational design, larger mother-and-singleton-offspring birth cohort, measurements of various parameters by trained professionals in the same specialized laboratory and sets of covariates. This study provides a better understanding of the combination of FDP and HDL-C (FHR), which could improve the detection of foetal growth disorders and potentially provide an effective and inexpensive indicator to predict the risk of delivering LGA/SGA infants. To the best of the authors’ knowledge, this is the first and largest study to determine associations between maternal FHR index and birthweight and delivery of LGA/SGA infants and to reveal the predictive value of FHR for the delivery of LGA/SGA infants in Chinese pregnant women. However, several limitations in this study should be mentioned. First, due to a lack of follow-up data on the clinical outcomes of offspring, whether FHR changes will affect long-term health outcomes and the occurrence of metabolic disease needs further study. Second, although multivariable adjusted regression models were applied, some uncollected or unknown factors might have an impact on LGA/SGA deliveries, such as maternal socioeconomic status, gestational weight gain, and history of GDM and LGA/SGA infant deliveries. Therefore, the effects of residual confounding factors cannot be excluded completely. Third, this is a retrospective single-centre pilot study, and selective bias is unavoidable. All of the subjects observed in this study were Chinese women, so the findings need to be confirmed in other ethnic populations.In this study, the FHR was used as an innovative indicator of foetal birthweight to examine associations between the maternal FHR before labour and foetal growth outcomes. This study found that an elevated FHR is associated with increased birth length and weight of infants and risk of delivering LGA infants and associated with decreased risk of delivering SGA infants. Furthermore, the FHR combined with traditional risk factors for delivering SGA and LGA infants have shown to increase predictive power. These findings suggested that the maternal FHR in late pregnancy could be a reliable and alternative indicator for predicting the delivery of LGA/SGA infants, representing an index worth taking into account when studying foetal birthweight-related changes. Considering the FHR in combination with routine risk factors is a simple and practical way to detect pregnant women at risk for delivering SGA/LGA infants, which may be helpful in a clinical setting and in obstetric management.Below is the link to the electronic supplementary material.Supplementary Material 1Supplementary Material 2


Kisspeptin is a neuropeptide with a primary role on the onset of puberty and has beneficial effects on ischemia/reperfusion (I/R) injury. In this study, we aimed to investigate the effect of kisspeptin administration on striatal I/R injury in mice.Forty adult C57/BL6 mice were randomly divided into four groups: Sham, Kisspeptin, I/R, and I/R + Kisspeptin groups. The groups were administered with either physiological saline (Sham and I/R groups) or kisspeptin (Kisspeptin and I/R + Kisspeptin groups) intraperitoneally 40 min before the operation. A microdialysis probe was placed in the right striatum according to stereotaxic coordinates. During the experimental period, artificial cerebrospinal fluid was passed through the micropump. Then, transient cerebral ischemia was established by compressing both common carotid arteries with an aneurysm clip for 15 min and animals were reperfused for 2 h. Throughout the process of microdialysis , samples were collected to measure dopamine (DA), noradrenaline (NA), and 3,4-dihydroxyphenylglycine (DHPG) at intervals of 20 min continuously. At the end of the reperfusion period, the animals were decapitated, striatum was dissected, half of the animals were used for oxidative stress analyses , superoxide dismutase (SOD), malondialdehyde (MDA), and the other half were used for histopathology analyses.Number of glial cells was significantly increased in kisspeptin-administered groups. DA levels in ischemic animals were decreased by kisspeptin administration (p < 0.0001). NA levels were reduced in animals administered with kisspeptin without I/R injury (p < 0.05). DHPG levels reduced during the reperfusion period in ischemic animals (p < 0.05). Kisspeptin did not exhibit a significant antioxidant activity in the ischemic animals, while GST and SOD levels were reduced in the I/R + kisspeptin group compared to the kisspeptin group (p < 0.05).Our results suggest that kisspeptin may be regulating the neurotransmitter release and metabolism, as well as inflammatory response in brain upon I/R injury. Cerebral ischemia/reperfusion (I/R) injury is a known complication of returning blood flow to ischemic brain tissue, and secretion of proteases and free radicals to the wounded area is a result of the reintroduction of oxygen and white blood cells via blood flow . CerebraThe prefrontal cortex circuits travel along a portion of the basal ganglion-caudate nucleus, globus pallidus, and thalamus . One of Kisspeptin receptor (Kiss1r) is found in various regions in the brain including pons, midbrain, thalamus, hypothalamus, hippocampus, amygdala, cortex, frontal cortex, and striatum as well as in the peripheral organs such as liver and intestine . KisspepIt is known that the striatum is more vulnerable than the cortex in ischemia ,24, and Experiments were performed in accordance with National Health Institute of Health Guidelines for the Care and Use of Laboratory Animals and ARRIVE guidelines with local government approval. Ethical approval was obtained from Local Ethics Committee on Experimental Animal Research . Forty young adult male C57/BL6 mice weighing 20–25 g were used in this study. As the menstrual cycle of the female animals and hormonal changes may have significant impact on the brain chemistry, male animals were used in the study. Animals were housed under controlled temperatures (21 ± 1°C) and controlled lighting conditions (12-h light/dark cycle). Standard mouse chow and tap water were provided ad libitum.The mice were anaesthetized with isoflurane  and placed on the stereotaxic frame, the microdialysis probe was placed in the right striatum according to the coordinates determined by the Mouse Brain in Stereotaxic Coordinates  by Paxinos and Franklin.  25]. Ex. Ex25]. After collecting microdialysis fluid samples at nine time points, the samples were stored at −80 °C for dopamine (DA), noradrenaline (NA) and 3,4-dihydroxyphenylglycol (DHPG) analyses. After decapitation, the striatum was dissected from the brain tissue. Reduced glutathione (GSH), glutathione S-transferase (GST), malondialdehyde (MDA), and superoxide dismutase (SOD) levels were measured to determine oxidative stress in the striatum. In addition, the brain tissues of the other five animals were used for the determination of histological alteration in the striatum by cresyl violet staining.At the end of the experimental period, the mice were decapitated and the brain tissues were frozen on dry ice. Tissues were sectioned coronally at 20 μm thickness using a Leica CM1850 UV Cryostat and immersed in different alcohol concentrations  for 5 min. Samples were stained with cresyl violet  for 5 min. After the staining, the slides were treated with different concentrations of alcohol  for 5 min and xylene for 20 min. Afterwards, sections were observed under a microscope with a fixed digital camera  at 40× magnifications. The total number of cells was counted in different groups at 150× magnifications. Images of sections were examined, and cell counting was performed by Fiji ImageJ software 1.5.2i (USA). Large cells with pale nuclear staining are marked as neurons and smaller round or oval nuclei without stained cytoplasm are considered glia. Small, elongated nuclei are considered epithelial cells and not included in our counts . Glial fAnalytical high pressure liquid chromatography column  with an electrochemical detector  system was used for catecholamine analysis. The temperature of the column furnace was fixed at 40 °C. Flow rate at the HPLC was set at 1 mL/min during analyses. Injections of 20 μL were performed. The modified catecholamine mobile phase solution with 32 mM citric acid , 16 mM sodium citrate , 0.9 mM sodium 1-heptanesulfonic acid , 0.16 mM EDTA , 36 mM tetrahydrofuran (VNR), 0.02 mM glacial acetic acid , and 0.616 mM Methanol  at pH 4.9 [GSH, GST, MDA, and SOD measurements were made spectrophotometrically. Changes in the levels of MDA in the striatum were analysed as reported by Placer et al. . The GSH® Prism statistical analysis software . Number of glia and neuronal cells were analysed by using one-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test. Catecholamine levels were analysed by using two-way ANOVA followed by Tukey’s multiple comparison test. GSH, GST, MDA, and SOD levels were analysed by using one-way ANOVA followed by Tukey’s multiple comparison test. A p-value lower than 0.05 was accepted as statistically different.The data were expressed as mean ± standard deviation (SD). Statistical analyses were conducted by using GraphPadHistological assessments of the ischemic injury in the corpus striatum revealed that I/R increased gliosis, while small amount of pyknosis was also observed in the Sham group . Microgl(t = -20) < 0.05) likely due to the individual differences in the animals in both groups (#p(t = 55 and 135) < 0.0001). DA levels were found similar in kisspeptin administered I/R animals (I/R + Kisspeptin) with the DA levels in the Sham and Kisspeptin groups  < 0.05; With regards to NA levels, there were no significant differences between the groups during the preischemia period . The Kispp < 0.05; During the preischemic period at t = −20, the Ischemia group exhibited significantly higher DHPG levels than the Kisspeptin group (p < 0.01) and I/R + Kisspeptin group  and arcuate nucleus of hypothalamus (ARC) [Kiss1 cells [TH and Kiss1 in AVPV/PeN has been illustrated, the function of DA produced in these cells was not clearly identified, and it was suggested that it might not be essential for puberty or reproduction processes [As known, the neuropeptide kisspeptin encoded by us (ARC) . In mices1 cells . Althougrocesses . Howeverrocesses . Adminisrocesses . On the rocesses .Kisspeptin was previously indicated to have beneficial effects upon I/R in the uterus and ovary . AnotherVarious psychosocial and physical stresses activate peripheral sympatho-adrenomedular and central catecholaminergic systems to increase circulating epinephrine and norepinephrine secretion. These stress hormones, known as catecholamines, trigger a series of biological reactions such as increased energy metabolism to prepare the organism to cope with stressful events and adapt . ChangesIn our study, we observed decreased NA levels in Kisspeptin group but not in I/R + Kisspeptin group. Previously, an increase in the metabolism of NA into DHPG , 78 in t2 [As a subgroup of glial cell populations, astrocytes have important roles in ischemic injury  by regul2  and tran2  influenc2 . Several2 , while a2 ,92. Addi2 . That maIn conclusion, our results suggest that kisspeptin may play a role in I/R injury by regulating neurotransmitter release, metabolism, and inflammatory activity in the infarct area. However, one should be cautious in interpretation when describing the beneficial effects of Kisspeptin on I/R. In addition to mechanical studies, longer reperfusion times are needed to observe the long-term effects of Kisspeptin on I/R injury.


Conventional wet Ag/AgCl electrodes are widely used in electrocardiography, electromyography (EMG), and electroencephalography (EEG) and are considered the gold standard for biopotential measurements. However, these electrodes require substantial skin preparation, are single use, and cannot be used for continuous monitoring (>24 h). For these reasons, dry electrodes are preferable during surface electromyography (sEMG) due to their convenience, durability, and longevity. Dry conductive elastomers (CEs) combine conductivity, flexibility, and stretchability. In this study, CEs combining poly:polystyrenesulfonate (PEDOT:PSS) in polyurethane are explored as dry, skin contacting EMG electrodes. This study compares these CE electrodes to commercial wet Ag/AgCl electrodes in five subjects, classifying four movements: open hand, fist, wrist extension, and wrist flexion. Classification accuracy is tested using a backpropagation artificial neural network. The control Ag/AgCl electrodes have a 98.7% classification accuracy, while the dry conductive elastomer electrodes have a classification accuracy of 99.5%. As a conclusion, PEDOT based dry CEs were shown to successfully function as on-skin electrodes for EMG recording, matching the performance of Ag/AgCl electrodes, while addressing the need for minimal skin prep, no gel, and wearable technology. I.There is an increasing demand for long-term electroceutical devices in clinical therapeutics, wearable interfaces, and neuroprosthetics. The current gold standard for skin surface biopotential recording applications is wet Ag/AgCl electrodes.et al.As an alternative to wet metallic electrodes, dry electrodes are very promising. They do not use an electrolyte gel, and therefore, they are able to be used for longer-term recording.However, there is a wide range of conductive elastomers presented in the literature based on various polymer carrier materials and conductive components. Most dry CE electrodes consist of an elastomeric carrier and a conductive filler.et al.et al.et al.et al.PEDOT:PSS based electrodes are, thus, a promising alternative, and they have been adapted in several studies for electromyography (EMG). Nijima et al.−1 at 20 wt. % and a range of properties related to an implant environment. These, thus, differ from other high-functioning elastomeric electrodes in the literature as they use thermoplastic polyurethane as opposed to the waterborne polyurethane electrodes produced by Zhang et al.et al. are already well-characterized and have been reported on several times for implantation studies.It is apparent that the elastomeric carriers that these conductive fillers are in contributed to the overall electrode function. The PEDOT:PSS is typically placed on or in thermoplastic or waterborne polyurethanes (TPU or WPU), polydimethylsiloxane (PDMS), foams, silicone, or integrated into various textiles to produce recording devices.So, this study focused on adapting 25 wt. % PEDOT:PSS/thermoplastic PU CE electrodes developed for implant devices to an sEMG setting.To interrogate this hypothesis, the aim was to compare the properties of wet Ag/AgCl and dry CE electrodes as skin contacting electrodes. This was achieved via electrochemical testing, functional EMG testing on the forearms of four subjects, and classification testing of the acquired EMG signals. For this, six electrodes were placed on forearm muscles corresponding to pre-determined movements .49–51 A CE electrodes were made into 1 cm squares, matching the active electrode area of commercial wet Ag/AgCl sEMG electrodes and the maximum recommended area per SENIAM guidelines.From a group of such movements, many studies determine the classification accuracy to compare electrodes as it is a realistic anticipation of the future application of the electrodes.II.A.et al.2. This value is two magnitudes smaller than the Ag/AgCl electrodes at low frequencies. This is significant because the useful frequency ranges of most bioelectric signals are typically below this, i.e., EEG: 0–50 Hz, electrocardiography (ECG): 50–100 Hz, EMG: 50–150 Hz, although EMG signals can be measured up to 10 kHz.The CE electrode mechanical properties and surface morphologies have already been investigated by Cuttaz Furthermore, the phase spectra and CV of the materials are critical to understand the charge transfer behavior of the electrodes . The Ag/The CV measurements further show the difference between CE and Ag/AgCl electrochemical behavior. Ag/AgCl electrodes show two small points of inflection  indicatiFurther EIS was performed on a phantom skin model, showing similar behavior in the CE electrodes . DespiteB.Electrodes were placed circumferentially on forearm muscles to record pre-determined movements. Specifically, wrist extension predominantly recruits the carpi radialis longus, carpi radialis brevis, and carpi ulnaris extensor muscles. The electrodes on top of these muscles dominate the EMG signal during extension whereas the anterior forearm electrodes receive a reduced signal. In contrast, flexion primarily recruits the palmaris longus and carpi ulnaris and carpi radialis flexor muscles. Thus, these electrodes on top of these muscles dominate during flexion. These two movements are, therefore, easily visually distinguishable. The fist movement recruits flexor digitorum superficialis muscle, which activates one or two of the anterior forearm electrodes. This makes it like the flexion EMG signal but still distinguishable based on the activated electrodes. The open movement primarily recruits the extensor digitorum, which is a smaller muscle and will, thus, produce a smaller EMG signal compared to extension, making it distinguishable in the posterior forearm electrodes.The extracted signals  were quaThe same six CE electrodes were used for all movements, trials, and participants, whereas the six Ag/AgCl electrodes were replaced between every participant in approximately 30-min intervals to prevent gel drying and the associated drift and artifact. The overall signal-to-noise ratio (SNR) of commercial Ag/AgCl electrodes was 15.7 ± 0.3 dB and of CE electrodes was 18.2 ± 0.3 dB (p < 0.0001). Despite the inter-subject variability displayed in the SNR, CE electrodes consistently maintained a significantly higher SNR than Ag/AgCl electrodes in all subjects (p < 0.0001) . Both thAdditionally, the baseline noise of the CE electrodes remained similar to the baseline noise of the Ag/AgCl electrodes across all subjects  and, thuC.To perform classification, the neural network requires inputs. The features extracted from the signal used as inputs are root mean square (RMS), standard deviation (SD), variance (VAR), mean absolute value (MAV), and wavelength (WL) . These sThe extracted data were used to train a Ag/AgCl BPANN and a PEDOT:PSS/PU BPANN and optimized by tuning multiple hyperparameters . The Ag/The Ag/AgCl neural network achieves its highest testing accuracy of 98.47% with analysis of all extracted features. Its training and validation accuracies are 99.49% and 99.13%, respectively . The PEDPrevious studies using PEDOT:PSS tattoo electrodes achieved an average classification accuracy of at least 90% with a support vector machine (SVM) neural network.et al.et al.Current gesture recognition systems have several uses, including wheelchair control, robotic hand control, prosthesis control, rehabilitative stimulation, and computer interface control by placing electrodes on hands, arms, legs, the face, and inside prostheses. Classification accuracies of Ag/AgCl and CE electrodes in these devices are typically 80%–100%.A known problem of dry electrodes is that a minimum baseline adhesion pressure is required to extract a viable signal.Previous studies have attempted to address this issue in two major ways: patterning and adhesive substrates. Patterning of microfeatures on a PEDOT:PSS electrode surface has taken on several shapes over the years. Penetrating microneedles, micropillars, suction cups, gecko feet, and topographical patterning have all been used to attempt to improve adhesion and connection with the skin, particularly when it has significant hair growth.III.In this proof-of-concept study, solid reusable CE electrodes exhibit the ability to produce EMG data similar or superior to gold standard wet Ag/AgCl electrodes. The CE displayed a significantly higher SNR (18.2 ± 0.3 dB) than the wet Ag/AgCl electrodes (15.7 ± 0.3 dB) (p < 0.0001). Both electrodes portrayed a stable signal throughout the experiment, while CE electrodes maintained a consistently lower signal drift, showing the ability of CE electrodes to be reused. However, the limit of reusability was not determined. Furthermore, the CE electrodes achieved a high classification accuracy of 99.57% on a CE-trained BPANN and 94.30% on an Ag/AgCl-trained BPANN. This indicates that solid CE electrodes can be used and implemented in existing movement classification frameworks.IV.A.Five males volunteered for this study. Exclusion criteria included neurological conditions affecting muscle and nerve conduction. One subject was excluded due to a severed ulnar nerve. Thus, four healthy males (20 ± 2 yr) were included in this study.B.Conventional wet Ag/AgCl electrodes (Neuroline 720 surface electrodes) are purchased from Ambu. Unless stated otherwise, all reagents were purchased from Sigma Aldrich. Thermoplastic PU elastomer pellets  were purchased from Velox GmbH. All circuit components were purchased from RS components, and the ADC (USB-1208FS-plus) was purchased from Measurement Computing. The armband used to secure CE electrodes was a size B tubular support bandage from Boots Pharmaceuticals.C.4). PEDOT:PSS was dispersed in the PU solution (25 wt. %) by stirring for 3 days at 60 °C. PEDOT:PSS/PU solutions were cast onto glass plates in a vacuum oven (BINDER GmbH) at an initial isotherm of 60 °C for 30 h.PU films were solvent cast from dimethylacetamide (DMAC) solutions containing 5 wt. % (w/v) PU. PU was dissolved in DMAC at 60 °C for 24 h prior to the addition of 0.16 wt. % (w/v) of lithium perchlorate  and the corresponding software Nova.Electrochemical characterization of CE films and Ag/AgCl electrodes comprised electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). Wet EIS and CV were conducted under ambient atmospheric conditions employing a conventional three-electrode cell, equipped with a platinum (Pt) counter electrode and an isolated Ag/AgCl reference electrode. Phosphate buffered saline (PBS) was used as the electrolyte. EIS was investigated by the application of a 10 mV sinusoidal voltage between the working and reference electrodes across the frequency range of 0.1 Hz–10 kHz. EIS on the skin phantom and human skin was conducted using a Spes Medica 35 × 45 mmF.A circuit board was independently produced, placing electrodes in four channels via a bipolar configuration. This allows the signal common to both electrodes, such as noise, to be attenuated and differences to be amplified with a gain of 100.G.Before testing, each participant's dominant forearm  was shaved and cleaned with isopropyl alcohol.(1)6 s of rest to establish baseline activity,(2)30 cycles of a 3 s maximal voluntary contraction (MVC) followed by 3 s of rest,(3)this is repeated for four more trials to a total of five trials, resulting in an overall 150 contractions per movement and 600 contractions per participant, and(4)the first four trials are used to train the neural networks, while the last trial is used to test the neural networks.For each movement, participants performed the following protocol:H.The input csv file has a binary column renamed “movement,” which takes a value of 1 during a MVC and a value of 0 during a rest period. Due to the recording protocol of repeating periods of 3 s of MVC and 3 s of rest, the movement column is a repeating pattern of 0 s followed by 1 s until the end of the recording. Acquired signals are processed via wavelet transform.I.https://github.com/ariehlev/Group-Project-Code) parses the movement column and saves the indices when there is a change in this column (from both 0 to 1 or from 1 to 0). This makes it possible to extract features for each MVC and resting period. The features extracted are RMS (root mean square), mean absolute value (MAV), variance (VAR), standard deviation (SD), and waveform length (WL). The equations are as follows:Features are extracted for each MVC and rest period. A produced algorithm  in previous studies.


Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya.This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis.We enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition . Most TB diagnoses  were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity  was independently associated with a shorter time to TB diagnosis as well as fatigue , and existence of a household contact diagnosed with TB , whereas older age , night sweats  and acute malnutrition  were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31.These results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV.NCT03862261, first registration 05/03/2019.The online version contains supplementary material available at 10.1186/s12879-023-08216-w. Tuberculosis is one of the top ten causes of death in children worldwide . In 2020In children, the laboratory-based diagnosis of TB is particularly challenging due to the paucibacillary nature of the disease and the difficulty to obtain respiratory samples for bacteriological confirmation . The diaMycobacterium tuberculosis and provide information on rifampin resistance  or extrapulmonary TB [EPTB]), and type of TB diagnosis . Children with bacteriologically confirmed TB were those from whom a biological specimen (i.e. sputum (expectorated or induced), gastric aspirate, nasopharyngeal aspirate, lymph node aspirate, cerebrospinal fluid, urine) was positive by smear microscopy, culture or WHO approved rapid diagnostics such as Xpert or LF-LAM. Children with clinically diagnosed TB were those who, based on symptoms, history, and sometimes radiologic abnormalities, had been diagnosed with active TB by a medical practitioner and received a full course of TB treatment.The prevalence of HIV coinfection among children presumed and diagnosed with TB was estimated together with the associated 95% confidence interval (CI). Demographic and clinical characteristics of children diagnosed with TB at enrollment were summarized using means (standard deviations) or medians (interquartile range) for continuous variables depending on distribution, and proportions for categorical variables, stratified by HIV status. To compare the characteristics between CLHIV and children without HIV (either HIV-negative or unknown status), Chi Square or Fisher’s exact tests of independence were used for categorical variables, whereas a Wilcoxon-Mann-Whitney test was used for continuous variables. Univariable and multivariable logistic regression was performed to identify the demographics and clinical presentations associated with HIV status, and with a reduced time to TB diagnosis. This latter analysis was performed because we noticed that HIV infection was associated with a shorter time to TB diagnosis and we felt important to measure this association after adjustment for other co-variates. Time to TB diagnosis was defined as the time from the month of onset of TB signs and symptoms to the month of TB diagnosis and was dichotomized to equal or less than 3 months versus greater than 3 months. Variables which had a p-value less than 0.2 in univariable analysis were then included in the multivariable model. A backwards method allowed retention of variables in the models with a significance of 0.05, while country and age  were forced in the models. Relevant interaction terms were also tested. Analysis was performed using SAS , Version 9.4.We finally compared TB treatment outcomes among CLHIV and children without HIV, using the WHO standard definition of treatment outcome assessed two months after treatment completion .No a priori power or sample size estimates were performed for this exploratory sub-analysis. We used the sample that was available from the INPUT study.See Additional file 1), 53/790, 6.7% (95%CI [5.1-8.7%]) were CLHIV. After TB investigations, one fifth  of the overall cohort was diagnosed with TB, they are the focus of this sub-analysis. A total of 37/157 (24%) participants were from Cameroon and 120/157 (76%) participants were from Kenya, with most children living in urban communities  (Table Of the 790 children enrolled in the INPUT study with TB signs and symptoms who were investigated for TB ((Table 1). Overall 50% (n = 11) CLHIV were screened for TB in the HIV clinic while the main entry point for children without HIV was the outpatient department . The proportion of children enrolled from the inpatient department was 18% (n = 28) and was similar in both groups.Among children with TB, 89/157 (57%) were male and the mean age was 1.5 years with 61% (n = 96) under the age of 2 years. CLHIV were significantly older than those without HIV . Respiratory symptoms, which consisted of dyspnea, cough, rhinitis, or cold, were reported as the reason for coming to pediatric entry points in 129/157 (85%) children. Cough was the most common symptom in both groups of CLHIV and children without HIV, followed by fever, night sweats, and appetite loss or failure to thrive (Table (Table 1).Overall, 57/157 (37%) had someone coughing in their household, they were 8/22 (36%) among CLHIV and 49/135 (37%) among children without HIV; 27/153 (17%) of children had a household contact on TB treatment ), loss of appetite or failure to thrive , abnormal pulmonary auscultation , pallor , pruritus  and moderate or severe acute malnutrition  ).Malnutrition (adjusted odds ratio (AOR): 3.16 [1.14–8.71], p = 0.027) and older age  were independently associated with a positive HIV status  of children (n = 96). Gastric aspirate was the main specimen type collected Table . Xpert wMost TB cases  were diagnosed clinically, however there is weak evidence of more frequent bacteriologic confirmation of TB among CLHIV  compared to children without HIV , p = 0.067.PTB was the most frequent presentation of TB in both CLHIV and children without HIV, 19/22 (86%) and 104/135 (77%), respectively. Of the 34/157 (22%) EPTB, 31 had lymph node TB (two were CLHIV), 2 had disseminated TB (one was a CLHIV) and 1 had osteo-articular TB (a child living without HIV).(Table 3).Overall, 105/157 (69%) of TB cases were diagnosed within 3 months after the onset of TB symptoms, 19/22 (86%) in CLHIV and 86/135 (66%) in children living without HIV, p = 0.08 ). In the final multivariate model, HIV positivity (AOR: 6.10 [1.32–28.17]), fatigue (OR: 6.58 [2.28–18.96]), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58–19.83]) were independently associated with a shorter time while older age (AOR: 0.35 [0.15–0.85]), night sweats (OR: 0.24 [0.10–0.60]) and malnutrition (AOR: 0.36 [0.14–0.92]) were associated with a longer time to TB diagnosis; p < 0.05.In univariable analysis of the factors associated with a shorter time to TB diagnosis, together with HIV positivity, the presence of cough, night sweats, fatigue, abnormal pulmonary auscultation, acute malnutrition, and existence of a contact coughing or being diagnosed with TB in the household carried significance at a level of 0.2. Thus, these covariates were included in the first step of multivariable modelling along with age, country and HIV status Table . In the CLHIV had more frequent malnutrition, and because HIV status and malnutrition had reverse effects on diagnostic delay , we further tested the interaction between them. It was found to not be significant. In other words, the effect of malnutrition on delayed TB diagnosis was similar in CLHIV and children without HIV.Two months after TB treatment completion, 10 children were classified as cured and 126 as having completed treatment   or unknown (n = 2) mothers, making it less likely that they would have been HIV-positive.Because we did not collect the weight-for-age z-score or mid-upper arm circumference but only determined if moderate or severe acute malnutrition was present (as per indicated in facility records), we were not able to assess if the classification of children with moderate and severe malnutrition was accurate based on standardized definitions. This potential inaccuracy is the reason why we decided to group children with reported moderate and acute severe malnutrition together in our analyses.Despite these limitations, this study gives important insights into specific clinical presentations and pathways to diagnosis of TB in CLHIV.In this sub-analysis of the INPUT study comparing children under age five years with TB-HIV co-infection to those with TB living without HIV in Kenya and Cameroon, we identified a lower-than-expected proportion of TB-HIV co-infection. Children with TB and HIV presented with malnutrition more frequently compared to those living without HIV. The use of LF-LAM in CLHIV contributed to bacteriologic confirmation of TB in these children. HIV positivity was significantly associated with a shorter time to TB diagnosis; however, children with malnutrition were diagnosed less rapidly. This altogether advocates for the need for better integration of TB services (including screening efforts and contact investigation) into all pediatric care entry points with a special focus on nutrition services, and for the importance of non-sputum-based TB diagnostics, especially in children living with HIV, to aid in more rapid diagnosis of TB.Below is the link to the electronic supplementary material.Supplementary Material 1


Health-related quality of life (HRQoL) reflects an individual’s own perception of their symptom burden, functional limitations, prognosis, overall health and changes associated with treatment. The HeartQoL is a validated heart disease-specific questionnaire with a physical and an emotional subscale that is used internationally to assess HRQoL in patients with coronary heart disease (CHD). The aim of this study was to translate and evaluate the psychometric properties of the HeartQoL in patients with CHD in Iceland.Patients ≥ 18 years  admitted with CHD were recruited from two hospitals in Iceland and completed the Icelandic versions of the HeartQoL, Short-Form 12v2 Health Survey (SF-12v2), and Hospital Anxiety and Depression Scale (HADS). A subsample of 47 patients completed the HeartQoL 14 days later. Confirmatory factor analysis for ordinal data was used to evaluate the measurement model with a physical and an emotional subscale. Convergent and divergent validity, internal consistency, and test-retest reliability were evaluated.α = 0.96) and emotional (α = 0.90) subscale. According to intraclass correlations (ICC), acceptable test-retest reliability was demonstrated (ICC = 0.79–0.86).Overall, the hypothesized two-factor structure of the Icelandic version of the HeartQoL was supported. However, problems with cross-loadings and correlated error variances were identified. Convergent and divergent validity were supported in correlational analyses between HeartQoL, SF-12v2, and HADS. Internal consistency reliability, measured by ordinal alpha, was good for the physical (With the two-factor structure confirmed, the Icelandic HeartQoL demonstrated satisfactory psychometric properties in the sample of patients with CHD. Users of the instrument can use the original scoring.The online version contains supplementary material available at 10.1186/s12955-023-02161-7. Cardiovascular disease remains the most common cause of disease burden in Europe, with coronary heart disease (CHD) its most common manifestation . PatientTo identify patient needs and evaluate intervention and treatment effects, HRQoL instruments, which come in two major designs — generic and disease-specific — need to be reliable, valid, and responsive –6. As geCoronary heart disease-specific HRQoL instruments have been designed for patients with heart failure, arrhythmias, angina pectoris, and myocardial infarction  with morThe HeartQoL has been psychometrically evaluated in 11 peer-reviewed publications in patients speaking at least one of 27 European languages, Mandarin Chinese, Persian (Farsi) and Malay  , evaluatTranslations of HRQoL instruments is another critical aspect that can have serious validity and reliability consequences. A poor translation process leading to a questionnaire that is not equivalent to the original language questionnaire limits the comparability of responses across populations with different languages or cultures . TherefoPatients with CHD were recruited from two main hospitals in Iceland between October 2017 and May 2019 for this psychometric study. All patients ≥ 18 years who were admitted electively or acutely for CHD  were eligible for the study. Information on age, sex, diagnosis, and treatment was collected from medical records. Eligible patients were asked to complete a battery of questionnaires at discharge. Patients who did not speak or write Icelandic and those unable or unwilling to respond to the questionnaire were excluded from the study.SD = 8.8) years; 315 (79.6%) were males; most patients were cohabiting  and had at least upper secondary education . A subsample (n = 47), of these 396 patients also completed the HeartQoL after 14 days to evaluate test-retest reliability. Patients who completed the test-retest assessment were significantly more often men (p = 0.031) with no age, cohabitation, education, or admission diagnosis differences. Detailed information about the sample is presented in Table A total of 446 patients consented to participate in the study; 50 patients had complete missing HeartQoL data, and the final sample included 396 patients (88% response rate). The mean age was 64.4   to assesThe 14-item HeartQoL is divided into two subscales, a 10-item physical and a 4-item emotional subscale. All 14 items are scored on a 4-point Likert-type scale ranging between 0 (‘A lot’) and 3 (‘No’). The subscale scores are calculated as the mean rating across the items with higher scores indicating better HRQoL . The HeaThe SF 12v2 is a 12-item, generic HRQoL instrument designed to measure health status from the patient’s perspective and covers eight health dimensions: Physical functioning (PF), Role physical (RP), Bodily pain (BP), General health (GH), Vitality (VT), Social functioning (SF), Role emotional (RE), and Emotional health (EH). Based on a scoring algorithm, each dimension has a possible score range between 0 and 100 with higher scores indicating better HRQoL. In addition, two component summary scores can be calculated, one each for physical (PCS-12) and mental (MCS-12) health . The insThe 14-item HADS is designed to screen for anxiety and depression. Each item is scored on a response scale ranging between 0 and 3, with subscale scores between 0 and 21 with higher scores implying more problems , 18. TheDescriptive statistics were used to present the sample, mean and standard deviations for continuous normally distributed data, median and quartiles for ordinal data, and frequencies for nominal data. Unpaired t-test and chi-square test were used to compare patients who did and did not complete the test-retest assessment. To consider the ordinal nature of item and scale scores, all analyses, except for the evaluation of test-retest reliability, were based on non-parametric statistics.rpc). Higher item-total correlations imply a higher discriminating capacity and should therefore be at least > 0.2 [Item analysis was used to evaluate the basic measurement properties on an item level . The scost > 0.2  with higCI), Standardised Root Mean Square Residual (SRMR), Comparative Fit Index (CFI) and Tucker-Lewis Index (TLI). Satisfactory model fit was defined according to Hu and Bentler [The factor structure was evaluated using CFA for ordered category indicator variables, that is, the weighted least squares means and variance adjusted (WLSMV) method, and polychoric correlations . Two CFA Bentler  with RMSrs) were used to estimate associations between the HeartQoL physical and emotional subscales and the PCS-12 and MCS-12 subscales. To support convergent and divergent validity, the strongest correlations are expected between similar constructs measured by different methods , while the weakest correlations are expected between different constructs measured by different methods . Convergent and divergent validity were also evaluated by correlating the HeartQoL scales with the eight health dimensions of the SF-12v2 and HADS subscales of anxiety and depression. To support convergent and divergent validity, the HeartQoL physical subscale should correlate more strongly with the SF-12v2 physical dimensions  while the HeartQoL emotional scale should correlate more strongly with the SF-12v2 mental dimensions . Further, the HeartQoL emotional subscale should correlate more strongly with symptoms of anxiety and depression measured by the HADS compared to the HeartQoL physical subscale. All analyses of the convergent and divergent validity were based on the original measurement model of the HeartQoL.Convergent and divergent validity were examined simultaneously using the multitrait-multimethod (MTMM) approach . SpearmaAn ordinal version of Cronbach’s alpha for Likert-type scales was used to estimate the internal consistency reliability on the original measurement model of the HeartQoL . OrdinalICC) ; values between 0.50 and 0.75, 0.75 and 0.90 and > 0.90 indicate moderate, good and excellent reliabilities, respectively [Test-retest reliability of the scale scores, based on the original measurement model of the HeartQoL, was evaluated using intraclass correlations , including the following packages: irr 0.84.1, lavaan 0.6–13, psych 2.2.9, semTools 0.5–6, sjmisc 2.8.9, and summarytools 1.0.1.Statistical significance was set at The study was approved by the National Bioethics Committee for Medical Research Ethics (17–159) and permission to examine patient records was granted by hospital authorities. The study was conducted in accordance with the Helsinki Declaration .rpc) were between 0.74 and 0.88 for the physical subscale and 0.74–0.81 for the emotional subscale, indicating good discrimination. Missing data among the items was low (2–4%) with item 13 not answered by 11% of the patients  or a positive skewed distribution with ceiling effects . The observed inter-item correlations (p = 0.085) and the 90% CI covered both the 0.05 and 0.06 criteria  with the weakest correlation between dissimilar constructs measured with different scales (rs = 0.35 and 0.29)  than with the mental dimensions . Similarly, the HeartQoL emotional subscale correlated more strongly with the SF-12v2 mental health dimensions (rs = 0.49–0.65) than with the physical dimensions (rs = 0.28–0.39). Furthermore, the HeartQoL emotional subscale correlated more strongly with HADS symptoms of anxiety and depression than the HeartQoL physical subscale . Despite the expected correlation pattern, the differences between the two subscales were minor regarding the SF (rs = 0.47 vs. 0.50) and RE (rs = 0.42 vs. 0.49) in the SF-12v2 and HADS depression (rs = -0.55 vs. -0.59)  and emotional (0.90) subscales. The corresponding traditional Cronbach’s alpha values were 0.93 and 0.84, respectively. Composite reliability was 0.96 and 0.90 for the physical and emotional subscales in the baseline CFA model and 0.85 and 0.63 in the modified CFA model  and emotional  subscales.Test-retest reliability was good for the HeartQoL physical  = 2.62, p = 0.009).Limitations of our study include the fact that, as this is a sub-study from a larger empirical study, no priori sample size calculation was conducted. Further, because of the restricted sample size with each diagnosis, we analyzed the group of patients with CHD as a single cohort. However, the sample size of 396 patients was considered large enough with 10–20 observations for each free parameter in the model . HoweverThe Icelandic version of the HeartQoL has sound measurement properties in patients with CHD. Users of the Icelandic HeartQoL can use the original scoring but should be aware of problems with cross-loadings and correlated error variances which may increase measurement errors for the physical and emotional subscales.Below is the link to the electronic supplementary material.Supplementary Material 1