For breast cancer (BC) with sentinel lymph node micrometastases (SLNMs), there are limited data to guide the selection of postoperative adjuvant therapy. This study aimed to identify target populations who might benefit most from adjuvant therapy and examine prognostic factors among patients with T1-2N1miM0 BC with one or two SLNMs who underwent sentinel lymph node biopsy (SLNB) alone.χ2 test. Univariable and multivariable Cox analyses were used to analyze characteristics predictive of Breast-cancer-specific survival and overall survival (OS). Kaplan–Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments.There were 7,423 patients diagnosed with T1-2N1miM0 BC between 2010 and 2015, and patients with one or two SLNMs were extracted from the Surveillance, Epidemiology, and End Results database. All the patients underwent SLNB alone without further axillary lymph node dissection, and they were stratified according to adjuvant therapy. The statistical significance of categorical variables was analyzed using the Adjuvant chemotherapy and radiotherapy improved 5-year OS rates. Multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and absence of radiotherapy were poor prognostic factors for OS. Patients who received breast-conserving surgery (BCS), and those with invasive ductal carcinoma (IDC), luminal A, luminal B, or basal-like subtype, and T1c or T2 stage benefited from adjuvant radiotherapy. Patients who received BCS, and those with IDC, luminal A subtype, and T1b, T1c, or T2 stage benefited from adjuvant chemotherapy.Our findings provide a clinical evaluation of treatment choice after surgery, which may help clinicians make individualized clinical decisions. A growing number of sentinel lymph node micrometastases (SLNMs) have been detected by the widespread application of SLN biopsy (SLNB) and advances in immunohistochemical detection for pathological diagnosis . For patThe ACOSOG Z0011  trial shTo help fill this lack of evidence, we investigated the role of adjuvant therapy in women with different molecular types of BC with one or two SLNMs who underwent SLNB alone. We also analyzed clinicopathological parameters, such as pathological grade, race, and T stage, which are known to contribute individually to prognosis. We searched the Surveillance, Epidemiology, and End Results (SEER) database for the indications for chemotherapy or radiotherapy and found high-risk factors that affected prognosis.There were 7,423 patients diagnosed with BC based on the International Classification of Disease for Oncology. The data for this study were acquired from the April 2019 release of the SEER database and were analyzed using SEER*stat version 8.3.6 software. We selected patients who were pathologically diagnosed with BC between 2010 and 2015 from 18 SEER registries, representing 33% of the USA population. Women with pT1-2 N1micM0 BC  were inThe exclusion criteria were as follows: male patients; >5 regional nodes examined; >2 positive nodes obtained; patients with secondary tumors or incomplete data; and patients who did not accept mastectomy or BCS.The following variables were retrieved for analysis: age; marital status; race; tumor grade, laterality, and histological type; surgery (mastectomy or BCS); adjuvant chemotherapy (yes or no); tumor molecular subtype and T stage; radiotherapy (yes or no); and molecular typing (estrogen receptor (ER), progesterone receptor (PR) and HER2 hormone receptor status). Grade III BC included poorly differentiated and undifferentiated histological grades. The SEER database did not categorize the axillary procedures performed. Therefore, surrogates were used to classify patients as having undergone SLNB or ALND. We defined SLNB if 1–5 LNs were removed and as ALND if >5 LNs were excised . The molχ2 test was used to test categorical variables. Univariate and multivariate Cox regression was carried out for OS and BCSS to identify independent risk factors. Variables with P < 0.1 in the univariate model were included in the multivariate model. Kaplan–Meier methods with the log-rank test was analyzed to compare survival difference between the different treatments. Subgroup analyses were also carried out to determine whether adjuvant therapy could benefit different groups.Breast cancer-specific survival (BCSS) and OS were the primary endpoints. OS referred to the survival time from diagnosis to death from any cause, and BCSS referred to the survival time from diagnosis to death related to the tumor. The P < 0.05 was defined as statistically significant. All statistical analyses were calculated using SPSS version 20.0 . The R programming language (version 3.3.1) was used to make forest plots. We used GraphPad Prism (version 7.0) software to generate Kaplan–Meier survival graphs.We analyzed 7,423 women with a diagnosis of pT1-2N1mic BC with one or two SLNMs between 2010 and 2015. We divided the treatments into the following four categories: no adjuvant therapy, adjuvant chemotherapy, adjuvant radiotherapy, and both adjuvant therapies . AdjuvanP < 0.1 in the univariate analysis included age, marital status, tumor grade, histology, surgery, tumor subtype, T stage, and chemotherapy or radiotherapy (P = 0.031); poorly differentiated and undifferentiated histology ; stage T2 ; triple-negative subtype ; single marital status ; or divorced . IDLC  predicted better OS. Nonreceipt of radiotherapy was correlated with decreased OS , but nonreceipt of chemotherapy was not associated with decreased OS .Variables with otherapy . All theP < 0.1 in our univariate analysis included age, marital status, race, tumor grade, histology, surgery, tumor subtype, T stage, and receipt of chemotherapy (P = 0.000) had poorer BCSS. Compared with patients with well-differentiated histology, patients with poorly differentiated and undifferentiated histology had decreased BCSS . Conversely, Luminal B subtype predicted better BCSS . Multivariate analyses also revealed that BCSS was not affected by: the type of surgery ; chemotherapy , T stage ; pathological type ; and age .Variables with otherapy . All of P = 0.128)  .To explore the specific subgroups that may benefit from chemotherapy or radiotherapy after surgery, subgroup analyses were carried out in the matched cohort , 2.P = 0.546). However, OS was significantly improved in patients who accepted radiotherapy and in those aged >50 years . The following factors contributed to significantly increased OS in patients who received radiotherapy: IDC ; grade I–IV ; tumor located left or right (both P < 0.05); undergoing BCS ; luminal A subtype ; luminal B subtype ; basal-like subtype ; T1c stage ; T2 stage ; and one or two SLNMs (both P < 0.05).We identified which specific subgroups may benefit from radiotherapy . We founP = 0.040) (P = 0.005); grade I–IV ; tumor located left or right (both P < 0.05); undergoing BCS ; luminal A subtype ; T1b stage ; T1c stage ; T2 stage ; and one positive SLNM .As for chemotherapy, stratified survival analysis showed that OS of nonreceipt of chemotherapy was elevated in patients aged 35–50 years who did not receive chemotherapy (= 0.040) . The folP = 0.000), compared with other pathological types, such as ILC (P = 0.187), IDLC (P = 0.208), and IDC mixed with other types of carcinoma (P = 0.326)  .P = 0.000, 0.014, and 0.012, respectively), but not patients with HER2 subtype (P = 0.355)  .P = 0.174), the survival rate of patients treated with BCS (P = 0.000) was increased by adjuvant therapy (Compared with patients receiving mastectomy ( therapy .P = 0.822). However, patients with T1b, T1c, or T2 stage tumors treated with adjuvant radiotherapy, chemotherapy, or both did show a significantly elevated OS, compared with the untreated group   .P = 0.000) (P = 0.011)  . For BCS= 0.011) .In the era of precision medicine, the treatment of BC is in transition toward a precise, minimally invasive, and individualized approach . The curOur multivariate analysis revealed that age ≥70 years, high grade, T2 stage, triple-negative subtype, and no adjuvant radiotherapy were poor prognostic factors for OS. Marital status was also a predictor of OS, single or divorced marital status predicted poor survival, which agrees with the study of Lan, who found that divorced or widowed marital status showed the highest mortality risk among BC patients with IDC .Pepels and Lupe reported , 11 poorThese high-risk factors need to be paid attention to. Our study found that old age predicted poor prognosis, while previous studies suggested that young age predicted poor prognosis, the different findings about age need further exploration.The current surgical consensus  states tP = 0.053) with only a follow-up of 23.3 months in the study by Wu et al. (Patients were stratified according to surgical procedures to identify target individuals who might benefit most from postoperative adjuvant therapy. The primary surgical procedures for BC include BCS and mastectomy, and the surgical method is associated with prognosis . In our u et al. . Similaru et al.  consideru et al.  showed tu et al.  proposedWe sought to establish whether age affected the selection of adjuvant therapy. We found a significant improvement in OS when patients aged >50 years received radiotherapy. It is generally believed that diagnosis of BC before 50 years of age is a high-risk prognostic factor ; therefoPatients with different molecular subtyping had different biological characteristics. Some researchers  believe St Gallen 2013 Consensus Guidelines Panel announced that the validity of chemotherapy did not rely on the number of positive nodes, but rather on the underlying tumor biology. We concluded that one rather than two positive nodes benefited from chemotherapy. The relationship between chemotherapy and the number of SLNs needs to be further explored.Conversely, the effectiveness of radiotherapy did not depend on the number of positive SLNMs. Houvenaeghel et al.  believedPrior studies have illustrated the relationship between different pathological types of BC and outcomes. Yang et al.  reportedGuiding treatment selection among patients with BC and SLNMs according to pathological T stage has been rarely studied. We showed that pT1c and pT2 stages were beneficial for adjuvant radiotherapy, while the pT1b, pT1c, and pT2 stages were beneficial for adjuvant chemotherapy. The pT1a stage did not benefit from both therapies. Our results require further verification. Moreover, the relationship between T staging and radiotherapy based on surgical methods or LN status  needs fuThe present study had several limitations. First, the study was restricted by its retrospective nature, and it was vulnerable to selection bias, in contrast to randomized controlled clinical trials. Second, its clinical and therapeutic features were limited to the USA. Third, details regarding radiotherapy such as dose, treatment volume, and radiation field were not available. Fourth, BC with SLNMs follows indolent behavior and persists for a long time , 30. ConHowever, this study also had the following strengths. Although the incidence of SLNMs was low, we had a high number of patients who met the enrollment criteria compared with other studies, and we predicted which breast patients may benefit from adjuvant therapy.Systematic and comprehensive individualized treatment regimens are needed after surgery in patients with BC and SLNMs. Tumor size, molecular subtyping, histopathological type, and type of surgery may affect the choice of adjuvant therapy. Our findings provide a basis for stratifying patients for radiotherapy and chemotherapy, to direct more personalized and refined therapy decisions. In the future, we need a more prospective, larger sample study with longer follow-ups to validate our results.


In pancreaticoduodenectomy, the pancreas-visceral fat CT value ratio and serrated pancreatic contour on preoperative CT have been revealed as risk factors for postoperative pancreatic fistulas. We aimed to evaluate whether they could also serve as risk factors for postoperative pancreatic fistulas after distal pancreatectomy.A total of 251 patients that underwent distal pancreatectomy at our department from 2006 to 2020 were enrolled for the study. We retrospectively analyzed risk factors for postoperative pancreatic fistulas after distal pancreatectomy using various pre and intraoperative factors, including preoperative CT findings, such as pancreas-visceral fat CT value ratio and serrated pancreatic contour.2), including 64 patients with diabetes mellitus (25.5%). Preoperative CT evaluation showed a serrated pancreatic contour in 80 patients (31.9%), a pancreatic thickness of 9.3 mm (4.0–22.0 mm), pancreatic parenchymal CT value of 41.8 HU (4.3–22.0 HU), and pancreas-visceral fat CT value ratio of − 0.41 (− 4.88 to − 0.04). Postoperative pancreatic fistulas were developed in 34.2% of the patients. Univariate analysis of risk factors for postoperative pancreatic fistulas showed that younger age (P = 0.005), high body mass index (P = 0.001), absence of diabetes mellitus (P = 0.002), high preoperative C-reactive protein level (P = 0.024), pancreatic thickness (P < 0.001), and high pancreatic parenchymal CT value (P = 0.018) were significant risk factors; however, pancreas-visceral fat CT value ratio (P = 0.337) and a serrated pancreatic contour (P = 0.122) did not serve as risk factors. Multivariate analysis showed that high body mass index (P = 0.032), absence of diabetes mellitus (P = 0.001), and pancreatic thickness (P < 0.001) were independent risk factors.The study population included 147 male and 104 female participants (median age, 68 years; median body mass index, 21.4 kg/mThe pancreas-visceral fat CT value ratio and serrated pancreatic contour evaluated using preoperative CT were not risk factors for postoperative pancreatic fistulas after distal pancreatectomy. High body mass index, absence of diabetes mellitus, and pancreatic thickness were independent risk factors, and a close-to-normal pancreas with minimal fat deposition or atrophy is thought to indicate a higher risk of postoperative pancreatic fistulas after distal pancreatectomy.The online version contains supplementary material available at 10.1186/s12893-022-01650-8. The postoperative pancreatic fistula (POPF) is the most clinically problematic complication of pancreatectomy. The incidence of POPF depends on the type of pancreatectomy. Distal pancreatectomy (DP), pancreatoduodenectomy (PD) with pancreaticojejunal anastomosis, and PD with pancreatic duct occlusion have reported POFP incidences of 16.0–28.2% , 10.3–18Thus, the aim of this study was to elucidate the risk factors for POPF after DP and to verify whether PVFR and serrated pancreatic contour could also serve as risk factors for POPF after DP, as they did for POPF after PD.Of the 259 patients who underwent DP at the Department of Hepatobiliary Pancreatic and Transplant Surgery of Mie University Hospital with a high volume of pancreatic resection during the 15-year period from January 2006 to December 2020, we excluded three patients whose preoperative CT images could not be referenced and five patients whose pancreatic parenchyma evaluations were difficult . The remaining 251 patients were identified as the study population , and the study conformed to the provisions of the Declaration of Helsinki. Informed consents were obtained from all the participants through an opt-out form. Participants were explained that they could opt out of participation by filling out an opt-out form. The study received ethical approval for the anonymization of patient data, the absence of risks to the patient, and the potential benefit for the adequate management of POPF based on unbiased information. All data were fully anonymized before we accessed them.Perioperative information and CT images were retrospectively extracted from medical records; univariate and multivariate analyses of risk factors for POPF after DP were performed. Preoperative factors that were evaluated in this study included age, sex, body mass index (BMI), history of preoperative diabetes mellitus (DM), diagnosis, history of preoperative chemoradiotherapy, and the hematologic examinations. Additionally, the preoperative nutritional scores evaluated included the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-neutrophil ratio (PNR).Intraoperative factors that were evaluated included operation time, intraoperative blood loss, surgical procedure (laparotomy or laparoscopy), combined splenectomy, combined portal vein resection, combined celiac axis resection, and simultaneous resection of the alimentary tract. Pancreatic texture could not be confirmed by laparoscopic surgery, and the description of pancreatic texture was omitted in the surgical records in some open surgery cases; therefore, this factor was not evaluated in the present study.POPF was defined and graded according to the International Study Group on Pancreatic Surgery (ISGPS) in 2016 , with GrCT examinations were performed using a multidetector CT scanner; Aquilion ONE  or LightSpeed 16VCT  between 2006 and 2011, Aquilion ONE or Discovery 750 HD  between 2012 and 2014, Discovery 750 HD or SOMATOM Force  between 2015 and 2018, and SOMATOM Force or Revolution EVO  between 2019 and 2020. After the non-contrast CT scan, a triple-phase contrast-enhanced CT scan was performed with a 1.25-mm slice thickness, including an arterial phase, a portal venous phase, and an equilibrium phase. Contrast material was administered intravenously by a power injector. The arterial phase was obtained using a bolus-tracking technique. The scanning delays of the portal phase were approximately 60–70 s, and those of the equilibrium phase were 130–180 s after the start of the contrast material injection.2 at sites where the vessels did not overlap while comparing the non-contrast CT with the contrast-enhanced CT; the mean CT values of the four measurements was calculated and adopted. The PVFR was calculated as the mean pancreatic parenchymal CT value / mean visceral fat CT value.To represent pancreatic fat deposition, the PVFR was determined from preoperative CT by using the method described in our previous report . The CT Pancreatic morphology was categorized as normal with a smooth margin (smooth type) or an irregular serrated pancreatic contour with protrusions of 3 mm or more (serrated type) Fig. . The panA total of 34 surgeons performed DP during the study period. Pancreatic stump closure for open surgery was performed using hand-sewn or stapled closure technique. In the case of hand-sewn occlusion of the pancreatic cut end, the pancreatic parenchyma was transected using an ultrasonic coagulation cutting device  followed by either main pancreatic duct ligation and suture ligation using the fish-mouth method. Regarding the staple closure technique, pancreatic parenchyma was divided with a bare or mesh-reinforced triple-row stapler  using a purple (3 mm) or black (4 mm) cartridge, selected by the surgeon according to the thickness of the transection line. In laparoscopic surgery, pancreatic stump was closed using a linear stapler or endoscopic hand-sewn technique as well as open surgery. None of the cases involved gastrointestinal anastomosis with the remnant pancreas or pancreatic duct occlusion . A closeThe basic postoperative and POPF management used in this study has been described in our previous report . Prophyl2 test. The significance level was set to P < 0.05; multivariate analysis was conducted using multiple logistic analysis, with variables showing significant differences in univariate analysis set as independent variables. The optimal cut-off value was determined using the Youden index from the receiver operating characteristic (ROC) curve. All statistical analyses were conducted using SPSS .The normality of data distribution was investigated using the Shapiro–Wilk test; parametric continuous variables were analyzed using Student’s t-test, and the non-parametric continuous variables were analyzed using a Mann–Whitney U test. Categorical variables were analyzed using a χWe retrospectively collected data from 259 patients who underwent DP at the Department of Hepatobiliary Pancreatic and Transplant Surgery of Mie University Hospital from January 2006 to December 2020. The institution is known to have a high volume of pancreatic resections. Three patients were excluded because their preoperative CT images could not be referenced. Another five were excluded due to difficulty in the evaluation of pancreatic parenchyma, and the remaining 251 patients were included in the present study.2 (13.6–34.7 kg/m2), and 64 patients had preoperative DM (25.5%); the most common diagnosis was pancreatic ductal adenocarcinoma . Preoperative therapy was performed in 67 patients (26.7%): chemoradiotherapy (CRT) was performed in 54 patients and chemotherapy in 13 patients. Thirteen PDAC patients received gemcitabine-based CRT between January 2006 and October 2011. Forty-one patients received S-1 + GEM (GS)-based CRT between November 2011 and December 2020, and the remaining 13 patients received GS chemotherapy. Our preoperative treatment strategies for pancreatic ductal adenocarcinoma have been described in a previous report [Table ative DM .5%; the Preoperative CT evaluation revealed a serrated type pancreas in 80 patients (31.9%) Table . The medCR-POPF developed in 86 patients 34.3%), including Grade B in 83 patients (33.1%) and Grade C in three patients (1.2%) , high BMI (P = 0.001), absence of DM (P = 0.002), high preoperative CRP value P = 0.024), pancreatic thickness (P < 0.001), and high pancreatic parenchymal CT value (P = 0.018) as risk factors  for BMI and 12.4 mm  for pancreatic thickness , absence of DM , and pancreatic thickness  were independent risk factors for CR-POPF Table . The optThe present study is the first to show that PVFR and serrated pancreatic contour, which are risk factors for POPF after PD, do not increase the risk of POPF after DP. However, high BMI, absence of DM, and pancreatic thickness were shown to be independent risk factors of POPF after DP.The incidence of POPF after DP differs between reports, but the results of a large-scale, multi-center, joint study in Japan in 2015  reportedThe previously reported representative risk factors for POPF after DP include obesity, younger age, malnutrition, and soft pancreas –13, but Several reports have performed risk factor analysis of POPF after pancreatic resection by using preoperative CT values, as we have focused on in the present study. In particular, a frequently used value is the pancreas/spleen CT value ratio (P/S ratio), obtained by dividing the pancreatic parenchymal CT value by the spleen CT value; it is based on the liver/spleen CT value ratio commonly used for evaluating fatty liver . The P/SThe following aspects can be considered as limitations of the present study: (i) this was a retrospective study with a small sample size from a single facility; (ii) the study period was long, potentially introducing various biases related to changes in postoperative management policies, surgical techniques, and pancreatic stump closure method; (iii) the evaluation of pancreatic morphology and CT value measurement method lacked objectivity; although criteria have been set for evaluation of pancreatic morphology, the influence of the evaluator’s subjectivity cannot be excluded; (iv) furthermore, CT value measurements were conducted so as not to overlap with the blood vessels and ducts in comparison with contrast-enhanced CT, but this process was not conducted mechanically, and there were problems with its accuracy. The conclusions drawn from the results of the present study should be interpreted in the light of these limitations and evaluated further in future studies.PVFR and serrated pancreatic contour evaluated with preoperative CT did not constitute risk factors of POPF after DP, unlike the findings for PD. High BMI, absence of DM, and pancreatic thickness have been shown to be independent risk factors, and the risk of POPF after DP is thought to be higher among those with a closer-to-normal pancreas with minimal fat deposition or atrophy.Additional file 1: Fig. S1. The number of enrolled cases each year in present study.


Type I short bowel syndrome (SBS) occurs after a critical reduction in the functional gut mass and resection of intestinal continuity after ileostomy or jejunostomy for necrotizing enterocolitis (NEC), intestinal atresia or other causes. SBS is often accompanied with intestinal failure-associated liver disease (IFALD) who requires long-term parenteral nutrition (PN). Our study aimed to observe the effect of intestinal continuity on the hepatic function of pediatric intestinal failure (IF) patients with type I SBS.The pre-and post-anastomosis medical records of 35 pediatric patients with type I SBS from April 2013 to April 2019 were reviewed retrospectively. The average growth (cm/month) in the proximal and distal small bowel lengths was calculated as the growth in intestinal length (cm)/the duration (month) from enterostomy to anastomosis. The changes in hepatic function from enterostomy to anastomosis were evaluated by assessment of hepatic function before anastomosis for 6 weeks and after anastomosis for 4 weeks.p < 0.05).The average growth in proximal intestinal length was 9.3 cm/month (±7.2) in neonates and 2.8 cm/month  in infants and children, and in distal intestinal length was 1.5 cm/month  in neonates and 0.4 cm/month  in infants and children. The incidence of IFALD was 28.6% 1 month before anastomosis and 20.0% 1 month after anastomosis (In pediatric type I SBS with IFALD, restoration of intestinal continuity may alleviate liver injury. There was an intestinal compensatory effect on the growth in the intestinal length after resection, and better results were seen in neonates in terms of intestinal length growth. Intestinal failure (IF) is caused by a constellation of conditions including a reduced absorptive surface area due to surgical or congenital loss of intestinal length, disorders of gastrointestinal motility, and congenital enterocyte defects , 2. The A total of 35 patients with type I SBS were admitted to the Division of Pediatric Gastroenterology and Nutrition and Department of Pediatric Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University from April 2013 to April 2019. In our study, the diagnosis of SBS was considered when a residual bowel length below a critical value for adequate nutritional supply and required PN for more than 42 days , 17. TheThe proximal length of the small intestine was measured as the residual intestinal length (cm) from the ligament of Treitz to the stoma, and the distal intestinal length was measured as the residual intestinal length (cm) from the stoma to the ileocecal valve. The length of the small intestine was measured separately at enterostomy and anastomosis, and the growth in the length of the small intestine (cm) was expressed as the difference in the lengths of the small intestine at anastomosis and enterostomy. The average growth (cm/month) in the proximal and distal intestinal lengths was calculated as growth in the length of the small intestine/the duration (month) from enterostomy to anastomosis.Hepatic function was assessed by the automated colorimetric method . The indicators of hepatic function included total bile acids (TBA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bilirubin (Tbi), and direct bilirubin (Dbi). The reference ranges were as follows: TBA, 0–10 µmol/L; ALT, 0–75 U/L; AST, 8–38 U/L; ALP, 42–121 U/L; GGT, 16–73 U/L; Tbi, 3–22 µmol/L; and Dbi, 0–5 µmol/L. The hepatic function was assessed before anastomosis for 6 weeks and after anastomosis for 4 weeks to evaluate the changes in hepatic function. The incidence of IFALD was recorded 1 month before and after anastomosis. IFALD was indicated when the serum levels of any three of the seven hepatic function indicators were two times higher than normal without other causes of liver injury including cytomegalovirus infection, viral hepatitis, biliary atresia, choledochal cysts, congenital infections, or metabolic diseases .Nutrition support included enteral nutrition (EN) and parenteral nutrition (PN). Total parenteral nutrition (TPN) was provided during the first few days after ileostomy, jejunostomy, or anastomosis. The “all-in-one” solution contained lipids , amino acids , a glucose solution, minerals, trace elements , water-soluble vitamins , and fat-soluble vitamins  and was infused continuously via peripherally inserted central catheters (PICCs) or central venous catheters (CVCs) by infusion pumps . We replaced the medium chain triglyceride/long chain triglyceride (MCT/LCT)-based lipids with fish oil-based lipids  when the levels of any three of the seven liver indicators were two times higher than normal. Enteral nutrition  was introduced by pumping for 1–3 h through a nasal tube every 3 h, and advanced gradually based on intestinal tolerance. PN was decreased and weaned off when EN increased sufficiently to sustain adequate growth.p value <.05 was considered to indicate statistical significance. The growth in the lengths of the proximal and distant intestine and duration from enterostomy to anastomosis were described separately in the population of neonates and infants and children. A paired t-test was performed for normally distributed data, and the Wilcoxon nonparametric test was used for non-normally distributed data. The incidence of IFALD was analyzed using Pearson’s chi-square test.The results are presented as n (%) for categorical data, mean ± standard deviation for normally distributed data, and median (interquartile range) for other types of data. SPSS 23.0 software for Windows  was used for statistical analysis. A n = 17, 48.6%), intestinal atresia , Hirschsprung’s disease (HD) , volvulus , and miscellaneous . Thirteen patients (37.1%) changed to fish oil-based lipids for 18 days  had undergone surgery as neonates. The etiologies were distributed across NEC , ALP (p = 0.006), and Dbi (p = 0.015) 2 weeks before anastomosis were significantly higher than those at 2 weeks after anastomosis, and Tbi (p = 0.015) was markedly lower at 4 weeks after anastomosis than before anastomosis. Regarding the hepatic function before anastomosis, Tbi (p = 0.000) was significantly higher at 2 weeks than at 4 weeks. As for the hepatic function after anastomosis, Dbi (p = 0.046) was significantly higher at 2 weeks than at 4 weeks. The incidence of IFALD 1 month before anastomosis (28.6%) was significantly higher than that at 1 month after anastomosis (20.0%) according to Pearson’s chi-square test (p < 0.05).Regarding changes in the hepatic function from enterostomy to anastomosis , there wOne of the most important management strategies in pediatric IF cases is providing sufficient fluids, electrolytes, and nutrients to maintain normal growth –3. ExcepIFALD is considered to be multifactorial and is the most frequent, even life-threatening, complication of pediatric IF resulting from long-term PN . IFALD cHowever, our study has some limitations. The retrospective data collection did not allow us to introduce accurate variables related to the initial clinical status, and the baseline characteristics of patients are difficult to standardize. The second limitation is that this was a single-center study with a small sample size which may weaken the statistical power and the validity of our conclusions. Although most IFALD cases are preventable and reversible, IFALD is still a potential cause of end-stage liver disease and remains one of the major indications for intestinal or combined liver and small bowel transplantation . TherefoIn pediatric type I SBS with IFALD, the restoration of intestinal continuity may alleviate liver injury. Additionally, there was an intestinal compensatory effect on the growth in intestinal length after resection, and the better results were observed in neonates with respect to the growth in intestinal length among the pediatric type I SBS population.


Atrial fibrillation (AF) is the most common and persistent form of arrhythmia. Recently, increasing evidence has shown a link between immune responses and atrial fibrillation. However, whether the immune response is a cause or consequence of AF remains unknown. We aimed to determine whether genetically predicted peripheral immunity might have a causal effect on AF.First, we performed Mendelian randomization (MR) analyses using genetic variants strongly associated with neutrophil, eosinophil, basophil, lymphocyte, and monocyte cell counts as instrumental variables (IVs). Lymphocyte counts were then subjected to further subgroup analysis. The effect of immune cell counts on AF risk was measured using summary statistics from genome-wide association studies (GWAS).P = 0.0070; OR, 1.10; 95% CI, 1.04–1.17; P = 0.0015; OR, 0.96; 95% CI, 0.93–0.99; P = 0.0359]. In addition, in our further analysis, genetically predicted increases in CD4 + T-cell counts were also associated with an increased risk of AF .Two-sample MR analysis revealed that a higher neutrophil count, basophil count and lymphocyte count had a causal effect on AF [Odds ratio (OR), 1.06, 95% confidence interval (CI), 1.01–1.10, Our MR analysis provided evidence of a genetically predicted causal relationship between higher peripheral immune cell counts and AF. Subgroup analysis revealed the key role of peripheral lymphocytes in AF, especially the causal relationship between CD4 + T cell count and AF. These findings are beneficial for future exploration of the mechanism of AF. Atrial fibrillation (AF) is the most common and persistent form of arrhythmia and one of the most important factors leading to increased mortality. Approximately 46.3 million people suffer from AF globally . In addiElectrical remodeling, structural remodeling, and autonomic nerve remodeling are the pathological basis of AF; the immune system is known to play an important role in this process , 4. InflAlthough these previous clinical studies have revealed an association between peripheral immunity and AF, granulocyte counts in peripheral blood, particularly neutrophils, have been associated with an increased incidence of other cardiovascular diseases, such as hypertension, coronary heart disease and diabetes –11. HoweTherefore, in this study, we selected single nucleotide polymorphism (SNP) data from large genome-wide association studies (GWAS) of hematologic traits as instrumental variables of exposure to assess the causal relationship between WBC counts and AF through a MR approach.Peripheral blood cell counts and AF candidate genetic instruments (SNPs) were selected from previous genome-wide association studies (GWAS). To prevent pleiotropic bias in cross-lineage cases , all indThree key assumptions needed to be met in the study design: (1) IVs were significantly correlated with interest exposure; (2) IVs were not associated with any confounders of the exposure-outcome association; and (3) IVs impact outcomes only through exposure .P-value of 5 × 10–8 for genome-wide significance, a linkage disequilibrium clustering algorithm with an R2 threshold = 0.001 over the 10 Kb region to ensure the independence of IVs exposure and allowing a minor allele frequency of 0.3 for SNPs in the palindromic region. Statistics relating to the association between these genetic variants and AF were then extracted as an outcome with a more relaxed aggregation threshold (R2 < 0.01). Following identification, Phenoscanner . Instrument strength was then assessed by the F-statistic which reflects the exposure variance explained by the instrument variables (via [PVE × (n – 1 – k)]/[(1 – PVE) × k], where n represented the effective sample size in the exposure GWAS, and k representsed the number of variants included in the IV model. To determine the power of MR outcomes, we use an online calculator1 to perform power estimation through a given type I error rate of alpha 0.05 and the OR from IVW estimates. A summary of information for the IVs used for MR analyses after clumping and data harmonization can be found in The proportion of variance explained (PVE) by each IV was used to explain the strength of the selected SNPs and was calculated as PVE = 2 × EAF × (1-EAF) × βariables . CalculaThe MR study was performed in R version 4.0.2  using the TwoSampleMR (TSMR) R package version 0.5.5. TSMR analysis was used to determine the causal relationship between peripheral immunity and HF in which the inverse variance-weighted (IVW) method was used to estimate the causal relationship between exposure and results . HighestThe datasets processed in this study were derived from GWAS –19. GWASP = 0.0070]. In addition, basophil counts were also observed to be associated with an increased susceptibility to AF in other leukocyte subtypes . However, lymphocyte count was inversely associated with disease risk , thus, suggesting the protective role of lymphocytes in AF. Sensitivity analyses showed no genetic polymorphism bias in any of the genetically predicted immune cell count analyses. LOO analysis further showed that the significance of the results was not driven by any single SNP. No obvious horizontal polytropism was found by visual inspection of funnel plots and analysis of MR-Egger regression intercepts. The results of the heterogeneity test, the polytropy test and the F-statistic are summarized in The analysis after evaluation and removal of SNPs associated with confounding is shown in + T cells, CD8+T cells, B cells, and unswitched memory B cells. If there were less than two IV variables available, Wald ratio results are shown instead of IVW and when there were fewer than three IVs, only IVW and CML-BIC are shown (P = 0.0493). An increase of NK cell count was associated with a protective effect on AF  and the NKT cell count was also negatively correlated with AF , although the results were not significant. However, we also observed that genetically predicted increases in CD4 + T-cell counts were associated with a higher risk of AF . In addition, due to the sample size, we did not observe a causal effect of other cell subtypes on AF risk and all results were supported by other MR methods.Next, we extended our analysis by further measuring causal estimates of the risk of AF by natural killer (NK), T and B cells in lymphocytes. Due to the small sample size of GWAS, we only evaluated eight lymphocyte subsets by MR, including NK cells, NKT cells, resting Tregs, secreting Tregs, CD4re shown . Our anaRecent studies have shown that considerable changes in the immune system occur during AF, including the recruitment and activation of immune cells and the secretion of their immune molecules induced by various factors; this is a process called immune remodeling . Immune Neutrophils are an important component of peripheral immunity and can increase AF susceptibility by releasing cytokines, such as IL-6, TNF-α, and IL-1β . In addi+ T can be activated by Toll-like receptor 2 (TLR2) and TLR4 to participate in the activation of AF (+ T cells can differentiate into different subsets of helper T (Th) cells. TH1 cells promote macrophage efficacy and mediate inflammation in AF by secreting interferon-γ (+ CD25 + regulatory T cells (Tregs) have been recognized to play an important role in maintaining peripheral tolerance and limiting inflammatory disease; furthermore, the depletion of Tregs can aggravate myocardial fibrosis (+ T in AF are rarely reported (+T cell counts and AF. However, our results do not indicate a causal relationship between genetically predicted other lymphocyte subtypes and AF, which means that more data from randomized clinical trials are still needed to explore their relationship.Lymphocytes play different roles in AF and the combination of different roles of different lymphocytes in AF constitutes the protective effect of total lymphocyte count in AF. NK cells could alter the local cytokine environment by preventing the maturation and trafficking of inflammatory cells. In the myocardium, NK cells can prevent the development of cardiac fibrosis by limiting collagen formation in cardiac fibroblasts and by inhibiting the accumulation of specific inflammatory populations and profibrotic cells in the heart ; this ison of AF . In resprferon-γ . In contrferon-γ . Th17 cerferon-γ . CD4 + Cfibrosis . Studiesreported . B lymphreported . The abnreported . To expl+ T cells. Our research enhances current understanding of the role of the peripheral immune system in AF. Further studies are now necessary to understand the relationship between different peripheral immune cells and AF and the underlying mechanisms.In conclusion, we demonstrate a causal effect of peripheral immunity on AF based on MR results obtained from large-scale aggregated GWAS data. In addition, the protective effect of total lymphocyte cell count in AF may be synthesized by the protective and promotive effects in NK cells and CD4There are some limitations to our study that need to be considered. First, the results of other MR methods are not entirely consistent with IVW methods in univariate MR analysis. We cannot completely exclude the possibility of pleiotropy in peripheral immunity and AF. Second, our study mainly included participants of European descent, which cannot be generalized to other ethnic groups , 52. MorThe original contributions presented in this study are included in the article/YF designed the manuscript. HT and XL revised the manuscript. All authors contributed to the article and approved the submitted version.


A balanced nutrition is important for children’s physical and cognitive development; yet, remains a challenge in many parts of low- and middle-income countries (LMICs). Early detection of nutritional deficiency and metabolic syndrome in school-aged children is necessary to prevent non-communicable diseases (NCDs) in later life. This study aimed at obtaining baseline data on health, nutritional status, and metabolic markers of NCDs among primary schoolchildren in Côte d’Ivoire.A cross-sectional survey was conducted among 620 children from 8 public primary schools located in the south-central part of Côte d’Ivoire. Underweight and overweight were defined as a body mass index  < 5th and 85th up to 95th percentile for sex and age, respectively. Dietary diversity of children was calculated based on a 24-hour recall conducted with the primary caretaker according to the guideline of Food and Agriculture Organization. Anaemia, malaria, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and blood glucose levels (HbA1c) were assessed, using capillary blood samples. Logistic models were performed to identify risk factors associated with overweight, HDL-C, LDL-C, and HbA1c.age 8.0 (± 1.7) years), 530 children attended school in a semi-urban and 90 in a rural area. Around 60% of children had a medium dietary diversity score (DDS). Children in peri-urban areas consumed more cereals . Most children were normal weight (n = 496), whereas 3.9% of children classified as prediabetic, 5% were underweight, and 15% overweight. LDL-C and HDL-C levels of children were associated with age, high DDS, and moderate anaemia. A significant association was found between prediabetes and malaria infection, as well as medium and high DDS. Overweight was associated with malaria infection and moderate anaemia.Among the 620 children (330 girls, 290 boys; MOverweight, prediabetes, low HDL-C, malaria, and anaemia are the main concerns of children’s health in Taabo. Our findings highlight interactions between infectious diseases, particularly malaria, and NCD risk factors. Monitoring NCD risk and infectious disease comorbidity in LMIC paediatric populations simultaneously is essential to better understand the dual diseases burden and apply early prevention measures.The online version contains supplementary material available at 10.1186/s12887-022-03684-6. Throughout the world, school-aged children suffer from various infectious and preventable non-communicable diseases (NCDs) . CurrentAn adequate nutritional diet is important in providing nutrients such as proteins, fats, vitamins, and minerals that are essential to the development, health, and wellbeing of individuals . OptimumPlasmodium falciparum for infants, inflammation for school-aged children, and iron deficiency for both school-aged children and women ) than high DDS. Compared to children with severe anaemia, those with moderate anaemia had 3.33 times increased odds of having abnormal HDL-C (OR = 3.33 [95% CI: 2.97–3.73]). Compared to children without malaria, those with malaria had 3.15 times increased odds of having abnormal HDL-C (OR = 3.15 [95% CI: 1.94–5.11])  and 2.64 [95% CI: 1.22–5.70] times (p = 0.014) higher in children with medium and high DDS, respectively, if compared to children with low DDS . Compared to children without malaria, those with malaria had 0.75 times decreased odds of being overweight (OR = 0.75 [95% CI: 0.68–0.83])  in our study was also consumed by the majority of the children in a study done in 2019 by Ayogu  in childConcerning the DDS of children, which is defined as the number of food groups consumed over a period of 24 h , around Similar to our study, a prior investigation in rural Nigerian schoolchildren reported that most children (78%) had medium DDS  and the P. falciparum infection were associated with younger age and being stunted.A key finding related to health status of schoolchildren was that in the present population, 5% of children were underweight and 15% were overweight. Our results are in line with those obtained in a study carried out in Togo (urban areas of Lomé) , where tBased on reference standards proposed by the Expert Panel of National Heart, Lung, and Blood Institute on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents , 43, morIn our sample of schoolchildren, approximately 4% were classified as prediabetic. These children are at increased risk of developing diabetes in later life . The preDiabetes should be considered a major health issue in Côte d’Ivoire. According to the integrated strategic plan for the prevention and management of NCDs in Côte d’Ivoire from 2015 to 2019, age-standardized prevalence of diabetes in individuals aged 18 years and above was 10.7% in 2014 . In 2017Our study has several limitations that are offered for consideration. First, we used parents/guardians’ recall of the child’s food intake in the previous 24 h. Using a single 24-hour recall period does not provide an indication of an individual’s habitual dietary behavior as there might be differences depending on the day of a week and according to seasons. Nevertheless, the recall period of 24 h is easier and less subject to recall error and it provides a valuable assessment of the diet at the population level and can be useful to monitor progress or target interventions . Second,Despite these shortcomings, our study sheds new light on the health status of children living in a low-income country and the risk for developing NCDs. The knowledge of children’s health status and the understanding of risk factor associated to their health status are important to follow them more closely for the planned implementation of a multi-country cluster randomized trial. As recommended by an expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents, attention should be paid to the cholesterol levels of children, because they are characterized by a considerable temporal stability and because they serve as a predictor of future CVDs in adulthood. Attention should also be paid to prediabetic children because children susceptible to abnormal carbohydrate metabolism have a markedly increased risk to getting diabetes-related CVDs later in life.We present one of the first studies to determine risk factors for NCDs among primary schoolchildren in a low-income country. Overweight, prediabetes, low HDL-C, malaria, and anaemia are the main concerns of children’s health in Taabo. Our findings highlight interactions between infectious diseases (ID) and NCD risk factors. Monitoring NCD risk and ID comorbidity in LMIC paediatric populations simultaneously is essential to better understand the dual diseases burden and apply early prevention measures.Below is the link to the electronic supplementary material.Supplementary Material 1


Several autografts are available to reconstruct the posterior cruciate ligament (PCL).Current scientific literature published in PubMed, Google scholar, Embase and Scopus.Hamstring, bone-patellar tendon-bone (BPTB), quadriceps and peroneus longus (PLT) are the most common tendon autografts used for primary isolated PCL reconstruction.The optimal tendon source for PCL reconstruction remains nevertheless debated. Identifying the most suitable tendon autograft could assist the surgeon during primary PCL reconstruction.The present study compared the outcome of PCL reconstruction using hamstring, BPTB, quadriceps and PLT autografts. The focus was on patient-reported outcome measures (PROMs), joint laxity, range of motion and complications.All autografts are viable options for PCL reconstruction, with BTB and hamstring autografts demonstrating superior PROMs. However, further clinical investigations are required to determine the ideal autograft construct. The following databases were accessed: PubMed, Google Scholar, Embase and Scopus. The following keywords were used for the search: ‘posterior cruciate ligament, autograft, graft, tendon, quadriceps, bone-patellar tendon-bone, hamstring, reconstruction, peroneus longus, BPTB, PCL, ligament, Lysholm, PROM, patient reported outcome measures, laxity, stability, instability, range of motion, anterior knee pain, reoperation, revision, pain’. Titles and abstracts were screened by the same authors in a separate fashion. If the abstract matched the topic of interest, the full text of the article was accessed. The bibliographies were screened to identify additional articles. Disagreements were resolved by a third author  reconstruction or other procedures were excluded. Studies that enhanced PCL reconstruction with cell therapies or experimental physiotherapy regimens were not suitable. Only articles which reported quantitative data under the outcomes of interests were considered for inclusion.Data extraction was performed by one author (A.P.). The following data at baseline were collected: author, year, journal, length of the follow-up, number of procedures, mean age of the patient age, percentage of women and type of autograft used. For each autograft, the following data were retrieved at last follow-up: Lysholm Knee Scoring Scale, International Knee Document Committee (IKDC), ROM, joint laxity measured by KT-1000 arthrometer, rate of revision and anterior knee pain.For the methodological quality assessment, the Coleman Methodology Score (CMS) was used.post hoc test was also performed. The confidence interval (CI) was set at 95% in all the comparisons. Values of P < 0.05 were considered to be statistically significant.The statistical analyses were performed by the main author (F.M.) using the STATA Software/MP . For descriptive statistics, mean and standard deviation was used. For dichotomic data, the frequency was estimated. Continuous data were analysed using the analysis of variance. The Tukey Honestly Significant Difference N = 203), comments, reviews, letters, notes, protocols, editorials, guidelines or registries (N = 301), biomechanical and/or cadaveric studies (N = 50), multiligaments reconstruction (N = 46), short duration of the follow-up (N = 13) and enhancing PCL reconstruction with other procedures (N = 37). A further 29 articles did not report quantitative data under the endpoints of interest. Thus, a total of 31 articles were eligible for this systematic review , followed by hamstring (88.5 ± 4.3), quadriceps (86.9 ± 4.6) and the peroneus longus tendon cohorts (81.7 ± 2.1) .The BPTB group reported the lower mean instrumental laxity (2.8 ± 0.9), followed by the hamstring (3.2 ± 0.9) and quadriceps tendon groups (3.0 ± 1.0) .Patients undergoing PCL reconstruction using hamstrings exhibited the higher IKDC (82.8 ± 2.7), followed by the PTL (79.7 ± 2.2), BPTB (75.3 ± 1.6) and quadriceps (74.5 ± 3.1) tendon groups .P = 0.8) autografts group , and the hamstring showed 0.8% (6 of 755). No revision was experienced by any patients of the PLT and BPTB cohorts. Anterior knee pain was observed in 9.1% (6 of 66) of patients in the BPTB group, and this was observed in 7.0% (3 of 43) in the PTL group and in 1.0% (7 of 735) in the hamstring group. No anterior knee pain was experienced by patients in the quadriceps group. The complications related to each graft are shown in detail in PCL reconstruction using an autologous ipsilateral BPTB graft and hamstring likely represents the most suitable graft for primary isolated PCL reconstruction. BPTB demonstrated the greater Lysholm score and the lower joint laxity at arthrometer. Hamstring produced the higher IKDC score. BPTB and hamstring evidenced similar ROM. BPTB and PLT are associated with the highest rate of anterior knee pain.,,,,,Hamstring is the most common autograft employed for cruciate ligament reconstruction.,PCL reconstruction with BPTB allows fast return to sport and enables bone-to-bone healing in ~4–6 weeks.,Quadriceps tendon autograft is a viable alternative for PCL reconstruction. Patients treated with a quadriceps tendon autograft reported satisfactory clinical outcomes, with optimal knee stability and quick return to preinjury level of activity.,PLT autografts are recommended for athletes who require dominant hamstring strengths to reduce the low incidence of anterior knee pain and kneeling pain.,,,,,,,,,,Several studies have compared the clinical outcomes of PCL reconstruction with autograft versus allograft and have demonstrated no significant differences in outcomes.The present study has several limitations. The design of the studies included for analysis was mostly prospective and retrospective, and only one randomized controlled trial was included. The limited study size along with the heterogeneous inclusion eligibility criteria were other important sources’ bias of the present study. The analyses were conducted irrespective of the type of the technique used for reconstruction (double or single bundle). The limited number of samples included for analysis may have jeopardized the reliability of these results. Thus, given these limitations, data must be interpreted with caution. Strengths of the present work were the comprehensive nature of the literature search along with the strict eligibility criteria and the adequate baseline comparability. The timing of the evaluation of the results was clearly indicated by most of studies. Most studies used outcome criteria with good reliability. The selection criteria were often reported and unbiased. Future high-quality studies involving a larger number of patients and longer follow-up are required to detect less common complications.The BPTB may represent the most suitable tendon for primary isolated PCL reconstruction. Further clinical investigations are required to infer solid conclusions.The authors have no potential conflicts of interest.This article does not contain any studies with human participants or animals performed by any of the authors.For this type of study, informed consent is not required.The data underlying this article are available in the article and in its online supplementary material.


This study is aimed at comparing the clinical outcomes of unprotected left main coronary artery disease (ULMCAD) treatment with contemporary percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in a “real-world” population. p=0.585). The primary end point was also comparable in a two propensity score matched cohorts. Ischemia-driven revascularization was more frequently needed in PCI than in CABG . By multivariate analysis, diabetes mellitus  and EuroSCORE  were the only independent predictors associated with long-term outcome.  Overall, 558 consecutive patients with ULMCAD  undergoing PCI or CABG were compared. The primary endpoint was the composite of death, nonfatal myocardial infarction, or stroke. Diabetes was present in 29% and acute coronary syndrome in 56%; mean EuroSCORE was 11 ± 8. High coronary complexity (SYNTAX score >32) was present in 50% of patients. The primary composite endpoint was similar after PCI and CABG up to 4 years (15.5 ± 3.1% vs. 17.1 ± 2.6%;  In a “real-world” population with ULMCAD, a contemporary revascularization strategy by PCI or CABG showed similar long-term clinical outcome regardless of the coronary complexity. Unprotected left main coronary artery disease (ULMCAD) is associated with increased risk of serious adverse events due to the large amount of myocardium at risk. Historically, coronary artery bypass grafting (CABG) was recommended as the revascularization strategy of choice for ULMCAD , 2. NeveLarge registries , 6 and rThis study aims to compare the clinical outcomes of ULMCAD patients treated with either PCI or CABG accomplished by contemporary technical and global clinical strategies, in a “real-world” population managed in a high-volume referral center.This study includes all consecutive patients who underwent revascularization for ULMCAD between 2013 and 2016 in our high-volume (PCI procedures >1500 per year and CABG interventions >500 per year) referral center. ULMCAD was defined as a de novo ≥50% stenosis of left main coronary artery at selective angiography. Patients with stable coronary artery disease, as well those with acute coronary syndromes, were included irrespectively of their coronary anatomy. All angiograms were scored according to the SYNTAX algorithm [nd generation DES. For distal left main disease, a single-stent technique was preferred in patients with a normal or diminutive appearing side branch, whereas a double-stent technique was considered in patients with disease of both ostia and proximal segments of left anterior descending and circumflex arteries. Regardless of the stenting technique used, routine final kissing balloon inflation and proximal optimization technique with noncompliant balloons was performed. Intravascular ultrasound guidance was strongly recommended.The clinical decision making process and the revascularization strategy choice were endorsed/shared by interventional cardiologist, cardiac surgeon, and referral cardiologist following the model of a “minimalist” Heart Team , 18 in pMultivessel disease was defined as stenosis >70% of >1 major coronary artery at baseline angiography. Anatomical-based definition of complete coronary revascularization was performed on post-PCI angiography evaluation as a TIMI flow grade 3 with residual stenosis <30% on visual assessment in the three main coronary arteries and their branches >2 mm of diameter achieved either during the index hospitalization or at any time within 30 days after ULMCAD PCI.Chronic antithrombotic treatment included aspirin  and ticagrelor 90 mg BID or prasugrel (5 or 10 mg daily as appropriate), or clopidogrel 75 mg daily for at least 6 months. Long-term DAPT >12 months) was strongly recommended . Patient months wμmol ADP ≥70% [According to our institutional protocol, all patients treated with clopidogrel, platelet reactivity was assessed by a light transmission aggregometry laboratory (LTA) test ; high on-treatment platelet reactivity on treatment (HTPR) was defined as residual platelet aggregation by 10 ADP ≥70% –23. All ADP ≥70% . UnschedCABG was performed using standard techniques to achieve a complete anatomical-based revascularization as defined for the PCI group. The use of off-pump technique and bilateral internal mammary arteries (BIMA) grafts were strongly recommended whenever possible. Intraoperative, transesophageal echocardiography was recommended to assess the ascending aorta and the ventricular and valvular function. In all patients aspirin was administered during the perioperative period. In patients undergoing CABG, antithrombotic therapy was administered according to current guidelines .The study was approved by the institutional ethics committee and complies with the Declaration of Helsinki. Informed consent has been obtained from all subjects or their caregivers.∗ plus ECG changes indicative of new ischemia, or development of pathological Q waves, or angiographically documented graft or native coronary artery occlusion or new severe stenosis with thrombosis and/or diminished epicardial flow, or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality [The primary study endpoint was a composite of all-cause death, nonfatal MI, or stroke at 4 years. All other endpoints  were considered as explorative. Cardiac death included death resulting from MI, heart failure, sudden cardiac death, and death due to cardiac procedures. Spontaneous MI was defined as the occurrence >72 hours after any PCI or CABG of the rise and/or fall of cardiac biomarkers >1x URLormality . Stroke All patients had scheduled follow-up visits at 1, 6, and 12 months and annually thereafter. All patients were contacted by telephone interviews to obtain 4-year follow-up. All other possible information gathered from hospital readmission charts or by referring physicians, relatives, or municipality vital registries, were entered into the prospective database.χ test was used to compare categorical variables, and the unpaired two-tailed Student's t-test or Mann–Whitney rank-sum test to analyze differences between continuous variables. Cumulative incidence curves were generated following the Kaplan–Meier method, assessing between groups differences with the log-rank test. Multivariable regression analysis to evaluate the independent contribution of clinical, angiographic, procedural variables to the primary endpoint was performed by Cox proportional hazards model. The variables entered into the model were revascularization strategy (PCI or CABG), SYNTAX score >32, diabetes mellitus, complete revascularization and EuroSCORE ≥13. The risk of overfitting was controlled by using a ratio of at least 1 : 100 for the number of variables and sample size. The proportional hazard assumption was assessed and satisfied graphically by plotting log (−log) survival curves against log survival time for each predictor category and verifying whether curves were parallel. We performed sensitivity analysis in order to test how robust the model was relative to the included population by assessing the effect of excluding STEMI patients.Categorical data are expressed as frequencies and continuous data as mean ± SD or median and interquartile range for normal and non-normal distributions, respectively. The A Cox proportional hazards model was also used to test interactions. In order to minimize the bias due to the nonrandomized nature of the study and the possibility of overfitting, a propensity score analysis was performed with a logistic regression model from which the probabilities for the type of revascularization (PCI or CABG) was calculated for each patient. The variables entered into the model were age, male gender, diabetes mellitus, ACS, left ventricular ejection fraction (LVEF) <40%, three-vessel disease, right coronary artery chronic total occlusion, SYNTAX score >32, and EuroSCORE. Model discrimination was assessed with the C statistic and goodness of fit with the Hosmer–Lemeshow test. A Cox multivariable analysis was then performed using the propensity score as a continuous covariate.p value <0.05 was considered significant. Analyses were performed with SPSS statistical package, version 21 .Matched analysis was also performed because of expected differences between PCI and CABG revascularization groups. An optimal data matching technique (1 : 1) was performed with a random order using the greedy-matching algorithm for propensity score difference and forcing the imbalanced characteristics . Bias reduction was assessed by comparing the standardized difference before and after matching between the 2 groups . After matching, the standardized difference changed from 67% to 9%. Four-year outcomes for the primary endpoint were assessed after matching by Kaplan–Meier analysis. Hazards ratio (HR) and their 95% confidence intervals (CI) were calculated. All tests were two-tailed. A p < 0.001, respectively, in PCI and CABG groups) and left ventricular dysfunction  were higher in the PCI group. Female patients were 107 (19%). Of them, 60 (20%) were treated with PCI, while 47 (17%) underwent CABG. Most of patients (84%) in PCI group were on DAPT with ticagrelor or prasugrel, while 34 (12%) were treated with clopidogrel; of them, 13 patients resulted HTPR and were escalated to a more potent P2Y12 inhibitor.Overall, 558 consecutive patients who underwent revascularization for ULMCAD  were included in the present analysis. Main baseline characteristics are summarized in Main angiographic and procedural characteristics are summarized in p=0.086). Conversely, the PCI group had a much shorter mean hospital stay .In the overall population, high-quality procedural standards were guaranteed by adherence to contemporary, guidelines-based strategies: all PCI patients received everolimus-eluting stents 2nd generation DES for left main stenting; rate of IVUS-guided stenting was 74%. Off-pump procedure and BIMA graft were adopted, respectively, in 81% and 58% of the CABG cohort. A complete revascularization was accomplished in 83% of the overall population and in 86% vs. 81% of the CABG and PCI group, respectively . Other explorative endpoints are reported in p=0.010). As depicted in p=0.736); equally, the revascularization strategy by PCI or CABG did not influence the outcome either in male or in female patients (The median follow-up length was 3 years (IQR 2–4 years). The cumulative incidence of the primary composite endpoint was similar in PCI and CABG groups up to 4 years: 15.5 ± 3.1% vs. 17.1 ± 2.6%, respectively, p=0.585 . Similarpatients .p=0.003) and HR 3.71; 95% CI 2.35 to 5.85; (p < 0.001), respectively ). Furthermore, the interactions between revascularization strategy vs. EuroSCORE >13 (p=0.605) and revascularization strategy vs. SYNTAX score >32 (p=0.112) did not resulted significant.At multivariable analysis, revascularization strategy by PCI or CABG was not independently associated with the composite primary endpoint, which was associated with diabetes mellitus and EuroSCORE  even aftp=0.599)).Also, in sensitivity analysis with exclusion of STEMI patients, revascularization strategy by PCI or CABG was not independently associated with the composite primary endpoint  and all-cause death  were similar in PCI and CABG groups, respectively. Similar results between PCI and CABG groups were found also in patients with high coronary complexity (left main and three-vessel disease): 17.2 ± 4.0% vs. 16.1 ± 3.9% p=0.634, in PCI and CABG groups, respectively.After propensity score matching (1 : 1), we identified 404 patients with balanced baseline characteristics that are summarized in The main findings of this “real world” registry, involving patients with ULMCAD treated with PCI or CABG, are as follows: (1) long-term primary composite endpoint of death, nonfatal MI, or stroke are comparable in PCI and CABG groups; (2) EUROScore and diabetes were the only variables independently associated with the composite clinical outcome; (3) the primary endpoint was independent of coronary complexity evaluated by SYNTAX score and revascularization strategy; and (4) female gender did not impact the clinical outcome, regardless of revascularization strategies by PCI or CABG.In the last decades, several studies and meta-analyses enrolling patients with ULMCAD showed comparable long-term outcomes, irrespective of revascularization strategy; nonetheless, patients undergoing PCI have an increased risk of target vessel revascularization , 26–30.The results of our study support that contemporary revascularization strategy by PCI or CABG in a “real-world” population are comparable in patients with ULMCAD, regardless of the presence of three-vessel disease and/or high complexity coronary anatomy.Our findings expand the results of recent RCTs to a “real-world,” unselected population characterized by a great burden of comorbidities, a high anatomic coronary complexity, and on average, a more critical clinical presentation compared to the selected population enrolled in trials. Indeed, patients enrolled in EXCEL and NOBLE trials were younger (median age: 66 years) and had a lower rate of ACS  and less comorbidities (mean EuroSCORE was 2%) than our study population. Remarkably, in our study population, the rate of patients with high coronary complexity (SYNTAX score >32) was 50%, whereas in the NOBLE trial was 8% and in EXCEL trial such patients were excluded by study protocol  .The favorable clinical outcomes in our study can be explained by the strict adoption of contemporary revascularization strategies for both PCI and CABG, including an updated antithrombotic therapy, the most complete revascularization possible, use of second-generation DES, high rate of intracoronary imaging in the PCI group and off-pump technique, and arterial grafts and BIMA in the CABG group. Conversely, some characteristics of the abovementioned RCTs , 11 mighOther large registries , 30 haveConversely, the results of a single-center study of Zheng et al. , conductWith the increasing numbers of RCTs comparing CABG and PCI, meta-analyses including more than 11,000 patients detected differences in clinical hard endpoints –37. In 4A further meta-analysis by Ahn et al. showed that a complete coronary revascularization by PCI or CABG provided similar survival rates both in patients with ULMCAD and in those with high anatomical coronary complexity (SYNTAX score >32) ; these fFindings of our registry support that when contemporary revascularization strategies are adopted in the clinical management of patients with ULMCAD, the only variables independently associated with the composite endpoint are EuroSCORE and diabetes. This concept is further strengthened by the fact that we did not find any interaction between revascularization strategy by PCI or CABG and EuroSCORE or complex coronary anatomy graded by the SYNTAX score. The high predictive and independent value of EuroSCORE in ULMCAD has been already reported in a previous work . In addiIn our registry, female gender, regardless of revascularization strategy, did not influence the clinical outcome at 4 years, confirming the results of the EXCEL trial posthoc analysis , in whicOur study must be evaluated in the light of several limitations. First, the observational, retrospective design precludes causal inferences. Despite the use of multivariable analysis, it remains unknown whether residual confounders may have affected our outcome. The high number of predictors screened might have resulted in overfitting. The propensity score-adjusted analyses should have reduced it; nevertheless, given the nature of the study, residual confounders cannot be excluded. Focusing our analysis on contemporary PCI or CABG strategies has precluded the exploration of much wider patient cohorts, which could have allowed a much longer follow-up. However, we are convinced that, despite the shortcomings that are inherent to all registries, the present study provides original and clinically valuable insights into the outcomes of interventional or surgical revascularization for LMCAD in a real-world perspective.In conclusion, the use of contemporary strategies aimed to obtain a state-of-the-art myocardial revascularization by PCI or CABG achieve similar outcomes, even in high-risk patients or complex coronary anatomy with ULMCAD. The clinical decision making process to choose the best management strategy for each individual patient, should take into account all the clinical characteristics, including functional and performance status, anatomic and procedural complexity, and not a merely high SYNTAX score as the main driver.


A novel electrochemical sensor designed to recognize and detect tartrazine (TZ) was constructed based on a molecularly imprinted polydopamine (MIPDA)-coated nanocomposite of platinum cobalt (PtCo) nanoalloy-functionalized graphene oxide (GO). The nanocomposites were characterized and the TZ electrochemical detection performance of the sensor and various reference electrodes was investigated. Interestingly, the synergistic effect of the strong electrocatalytic activity of the PtCo nanoalloy-decorated GO and the high TZ recognition ability of the imprinted cavities of the MIPDA coating resulted in a large and specific response to TZ. Under the optimized conditions, the sensor displayed linear response ranges of 0.003–0.180 and 0.180–3.950 µM, and its detection limit was 1.1 nM (S/N = 3). The electrochemical sensor displayed high anti-interference ability, good stability, and adequate reproducibility, and was successfully used to detect TZ in spiked food samples. Comparison of important indexes of this sensor with those of previous electrochemical sensors for TZ revealed that this sensor showed improved performance. This surface-imprinted sensor provides an ultrasensitive, highly specific, effective, and low-cost method for TZ determination in foodstuffs. Tartrazine TZ,  is an arSensitivity and specificity are two important factors governing the performance of electrochemical sensors . TZ contMIPs are also called “artificial antibodies” and have been used in solid-phase extraction, molecular recognition, chromatographic separation, drug delivery, biological engineering, and biomimetic sensing. For MIP-based electrochemical sensors, the electrocatalytic activity and microenvironment of the imprinted cavities are the most important factors influencing sensor performance ,8. ThereA simple, rapid, and cost-effective method for quantitative analysis of TZ with high sensitivity and selectivity still needs to be developed. Herein, a novel MIP nanocomposite sensor for TZ is prepared by grafting an ultrathin membrane of molecularly imprinted polydopamine (MIPDA) onto the matrix surface of platinum cobalt nanoalloy-functionalized graphene oxide (GO–PtCo). The sensitivity and selectivity of the developed electrochemical sensor in TZ detection are investigated.2PtCl6·6H2O), cobalt chloride hexahydrate (CoCl2·6H2O), sodium borohydride (NaBH4), Allura Red, sunset yellow, amaranth, brilliant blue, indigo carmine, sodium salicylate, vitamin C, glucose, sucrose, citric acid, benzoic acid, phenol, and sodium acetate were purchased from the Aladdin Chemistry Co., Ltd. . Other chemicals were purchased from the Shanghai Chemical Reagent Co. . All chemicals were of analytical grade and used without further purification. The drink and food samples were purchased from local markets. Double-distilled deionized water was used throughout this work.Tartrazine (TZ) and dopamine hydrochloride (DA) were purchased from Sigma-Aldrich . Graphite, hexachloroplatinatic acid hexahydrate  with a conventional three-electrode system, including a modified GCE (diameter: 3 mm) as a working electrode, a Pt wire supporting electrode, and a saturated calomel reference electrode. Surface morphological images were recorded using a scanning electron microscope  and a transmission electron microscope . All experiments were carried out at room temperature unless otherwise noted.Graphene oxide (GO) was prepared from graphite powder using a typical method with some modifications . Typical2PtCl6·6H2O (3.424 mg) and CoCl2·6H2O (0.523 mg) were added and the mixture was stirred for 24 h. Fresh NaBH4 (24 mg in 10 mL of water) was added quickly into the mixture, which was then stirred for 2 h. The products were collected by centrifugation, washed with deionized water to remove unreacted reagents and impurities, and then dispersed in water (20 mL). Other nanoalloy particles were prepared by adjusting the amounts of materials added to the precursor solution. GO–Pt and GO–Co were prepared by the same procedure in the absence of CoCl2·6H2O or H2PtCl6·6H2O, respectively.PtCo nanoalloy-decorated GO (GO–PtCo) was synthesized by consulting the reported method ,14,15. IVethanol:Vconcentrated ammonia:Vwater = 7:2:1) to extract the TZ template molecules. Washing was repeated until no template molecules were detected in the extraction solution, and then the product was rinsed thoroughly with distilled water. Other imprinted nanocomposites were synthesized via a similar process by changing the concentration of TZ template molecules or DA. For comparison, non-imprinted PDA-coated GO–PtCo was prepared by the same procedure in the absence of the TZ template molecules; the product was denoted as GO–PtCo@NIPDA. The template extraction process was also performed on the control GO–PtCo@NIPDA composite.In a typical synthesis of MIPDA-coated GO–PtCo (denoted GO–PtCo@MIPDA), DA (15 mg) and TZ (15 mg) (molar ratio of ~7.4:2.6) were dissolved in water (30 mL) under ultrasonication for 1 h in ice water. The mixture was added to the above GO–PtCo dispersion. The pH of the mixture was adjusted to 8.5 with Tris–HCl buffer solution. The mixture was strongly stirred for 24 h at room temperature. After the reaction, the product was centrifugally washed with water to remove any unreacted monomers, and then immersed in a basic mixture (Q = V(c0−cS)/m, where V represents the solution volume, c0 and cS are the TZ concentrations before and after adsorption, respectively, and m is the mass of material.The GO@MIPDA, GO–Pt@MIPDA, GO@NIPDA, and GO–Pt@NIPDA nanocomposites were synthesized via a similar procedure to GO–PtCo@MIPDA and GO–PtCo@NIPDA using GO or GO–Pt as the matrix. Adsorption experiments were conducted as follows. Each material (3 mg) was added to TZ solution  for 12 min to recover the functional surface of GCE/GO–PtCo@MIPDA before the next measurement. Other modified electrodes, including GCE/GO, GCE/GO–Pt, GCE/GO–PtCo, GCE/GO@NIPDA, GCE/GO–Pt@NIPDA, GCE/GO–PtCo@NIPDA, GCE/GO@MIPDA, and GCE/GO–Pt@MIPDA, were prepared in a similar manner to GCE/GO–PtCo@MIPDA.A bare GCE was polished with slurry alumina (0.3 μm and then 0.05 μm) and then washed with water with the aid of ultrasonication. GO–PtCo@MIPDA suspension  was carefully dropped onto the surface of the GCE. A GO–PtCo@MIPDA film-coated GCE (denoted GCE/GO–PtCo@MIPDA) was obtained through self-assembly during solvent evaporation in air. For repeated detection using one electrode, the electrode was dipped in agitated eluent solution (Each three-electrode system was assembled in a cell with 0.2 M acetate–sodium acetate (Hac–NaAc) buffer solution containing a certain concentration of TZ. After the sensor was immersed in solution for 10 min under mild magnetic stirring to reach adsorption equilibrium, a CV or DPV was recorded unless otherwise noted. For the detection of TZ in drink and food samples, corresponding 1.0 g/L solutions were used as detection samples. Before TZ detection in these samples, the pH of the prepared water samples was adjusted to 6.0, and the DPV peak corresponding to TZ in the real samples was recorded to reveal the amount of TZ in each sample.Graphene oxide (GO) is known as an ideal matrix for in situ nucleation, growth, and anchoring of naked metal nanoparticles because of its functional groups and lattice defects, ultrahigh mechanical strength, and large planar structure. A one-step method that involved reducing a metal precursor in GO solution was used to form the GO–PtCo composite in situ ,14,15. SCyclic voltammetry (CV) was employed to investigate the electrochemical performance of the materials . GO exhiSurface-imprinted polymers are increasingly being used as specific recognition elements. Considering the attractive properties of PDA, including abundant functional groups, a cross-linked structure, and robust adhesiveness ,17,18,19According to the above investigation, it is clear that GCE/GO–PtCo@MIPDA had a high sensing ability for TZ. To achieve better sensing performance, the experimental conditions should be optimized, including the nanoalloy composition, the molar ratio of DA to template molecules, the amount of DA monomer, incubation time, elution time, pH, and adsorption kinetics.2-bonded carbon atoms arranged in a two-dimensional honeycomb lattice that is one atom thick and has numerous oxygen-containing groups on the basal plane and edges [The GO skeleton is composed of spnd edges . It is wnd edges . To inveMIPDA was prepared via DA self-polymerization. The content of imprinted cavities in the MIP was directly affected by the ratio of template molecules to functional monomers, which further affects the rebinding and recognition abilities of the prepared sensor. Therefore, the currents of imprinted nanocomposites produced using a series of DA:TZ molar ratios of 9:1, 8.5:1.5, 8:2, 7.4:2.6, 7:3, 6.5:3.5, and 6:4 in MIPDA synthesis were recorded ; the totThe peak currents obtained when the quantity of DA was altered while keeping the DA:TZ ratio at 7.4:2.6 during the self-polymerization process for 24 h are shown in It is known that the thickness of a PDA film can be controlled by modulating the polymerization time, which also affects the depth of the imprinted cavities. Therefore, the synthesis period of the MIP nanocomposite was studied. As shown in The GCE/GO–PtCo@MIPDA sensor was incubated in TZ solution for different times at room temperature and then the response current was measured. As shown in Vethanol:Vconcentrated ammonia:Vwater = 7:2:1) was used as the eluent to remove TZ; good results were achieved. To reuse GCE/GO–PtCo@MIPDA, the adsorbed TZ needed to be removed to recover its molecular recognition ability. In this experiment, a basic mixture (ipa) increased with pH from 5.0 to 6.0 and reached a maximum at pH = 6.0. Then, ipa decreased as the pH increased from 6.0 to 7.5  from GCE/GO–PtCo@MIPDA exhibited linear relationships with TZ concentration (C) in the ranges of 0.003–0.180 and 0.180–3.950 µM, with regression equations of ip (μA) = −113.3156 × C (μM) − 0.03219 (R2 = 0.9983) and ip (μA) = −22.0380 × C (μM) − 16.4604 (R2 = 0.9989), respectively. The detection limit was 1.1 nM (S/N = 3). When C was above 3.950 μM, the calibration curve gradually deviated from the straight line, indicating that saturated adsorption was gradually reached. A linear range of 0.040–9.650 μM and detection limit of 16.5 nM were obtained for GCE/GO–PtCo  gives better peak shape and higher sensitivity than CV. As shown in /GO–PtCo . The detThe binding selectivity of GCE/GO–PtCo@MIPDA for TZ and other structural analogs, which are possible coexisting additives that may be present with higher concentrations, was evaluated by competitive experiments. As shown in The reproducibility of the response of GCE/GO–PtCo@MIPDA was estimated by detecting a 0.15 µM TZ solution with six different electrodes prepared under the same conditions. The current response showed a relative standard deviation (RSD) of 3.25% for six independent measurements. A RSD of 4.17% was obtained after 20 cycles of washing and measurement, and the signal strength decreased to 95.00% of the initial strength after 75 cycles, indicating the good reproducibility and excellent recyclability of the sensor. Moreover, the stability of the sensor was evaluated by storing six independently fabricated electrodes for six weeks at room temperature. The peak current did not change markedly over the first two weeks. After six weeks, the average signal was 96.04% of the initial response. These measurements indicate that GCE/GO–PtCo@MIPDA possesses suitable reproducibility and stability for successful use as a sensor.The practical application of the electrochemical sensor was assessed by detecting the TZ levels of different samples . The recOver the past decade, TZ has been detected using numerous electrochemical methods. The analytical performance of the MIPDA sensor for TZ was compared with that of previous TZ assays using well-known technical indicators for analytical methods, including linear interval, detection limit, recognition component, anti-interference ability, and recovery from real samples . The MIPThe surface of the GO-modified electrode exhibited a small anodic peak response to TZ, which was not displayed by the bare electrode surface, indicating that there are electrochemically active sites on GO for configuration-suitable molecules within the diffusion layer a. LargerUnder alkaline conditions (pH > 7.5), DA is first oxidized by oxygen to DA quinone, followed by 1,4-Michael-type intramolecular cyclization to yield leucodopaminechrome. Leucodopaminechrome undergoes further oxidization and intramolecular rearrangement to form 5,6-dihydroxyindole and its isomer, which subsequently polymerize to give PDA, a melanin-like polymer with a cross-linked structure. PDA obtained by self-polymerization of DA tends to coat diverse substrates as a thin film, especially GO and metallic surfaces. It is generally accepted that the catechol group plays the central role in the mussel-mimicking behavior of PDA ,17. The Usually, surface MIP composites are prepared by polymerizing cross-linkers, functional monomers, and template molecules through covalent or non-covalent interactions via various routes, including free-radical polymerization, reversible addition–fragmentation chain transfer polymerization, atom transfer radical polymerization, and the sol–gel method. An imprinted hybrid material with recognition ability is obtained after removal of the embedded template molecules . Here, tTo construct imprinted composites with effective electron transfer surfaces, good interfacial bonding and interactions between the matrix and MIPs are very important. TZ was first mixed with DA in water to induce molecular self-assembly via intermolecular forces, such as hydrogen-bonding and π–π and electrostatic interactions. During DA self-polymerization, template TZ molecules were embedded in the PDA through intermolecular forces. The embedded TZ molecules were closely anchored to the GO–PtCo surface with a configuration suitable to allow effective electron transfer. Due to the small dimensions and the extremely high surface-to-volume ratio of the imprinted molecules, most were situated at or close to the matrix or metal surface to form a stable state. After the removal of embedded template molecules, three-dimensional imprinted cavities complementary to the template molecules in terms of shape, size, and functional groups were formed; these cavities could rebind template molecules with high specificity. This laid the foundation for the manifested high selectivity of the electrochemical sensor, combined with the electrocatalytically inert MIPDA surface, which helped to prevent interference from other materials. Therefore, GO–PtCo@MIPDA displayed an obvious preconcentration effect by binding to TZ in a suitable configuration, increasing the local amount of TZ compared with that in the diffusion layer near GO–PtCo. The electrochemical behavior of GO–PtCo@MIPDA towards TZ indicated that the layer of MIPDA must be ultrathin and that the PtCo surface in the cavities might be nearly bare, which increased the electrocatalytic activity for TZ. Therefore, the strongest electrical sensing signal was effectively transferred to the electrode via the highly specific GO–PtCo@MIPDA interface. These interesting phenomena could be ascribed to the combined effects of the highly electroactive surface of PtCo and the specificity of the imprinted cavities for TZ ,25,26.Overall, GO–PtCo@MIPDA combined the synergistic effects of the conductive matrix of GO, high electroactivity of PtCo, specific recognition cavities in MIPDA, and the blocking effect of MIPDA to interfering molecules. These combined features led to the achieved excellent electrochemical response and selectivity of GO–PtCo@MIPDA, making it attractive for sensing applications.PtCo nanoalloy particles were synthesized on the surface of GO in situ and the obtained nanocomposite exhibited facile electrocatalysis of TZ. After the surface of GO–PtCo was coated with MIPDA, an electrochemical sensor for TZ with ultra-high sensitivity, high selectivity, good reproducibility, and long-term stability was obtained. The ultra-high sensitivity was ascribed to the facile electron transfer between the TZ-enriched cavities with a suitable configuration and the highly electrocatalytically active surface of GO–PtCo. The highly selective electrochemical surface for TZ was achieved through the MIPDA cavities that specifically matched TZ and the rest of the PDA coating behaving as an electronic barrier to other molecules. The good reproducibility and stability obtained were also related to the synergistic effect between the GO matrix and the imprinted polymer. This sensor showed potential for use in TZ determination and represents a strategy that may be adopted for other molecules. In the future, it will be important to research further heterogeneous composites of nanoalloys and graphene, the imprinting applications of polydopamine, signal transduction, and synergistic sensors.


Monthly phytoplankton biomass at each station in July-September 2017 was aggregated by class . Zooplankton biomass in September 2017 was aggregated by major taxa ). Environmental variables monthly monitored in January-October 2017 included salinity, concentrations of dissolved organic carbon, humic substances, total nitrogen and total phosphorus. These variables were measured from 0 to 10 m depth below water surface, and the depth-integrated averages were used for data analyses. Seston and zooplankton  FA compositions were analyzed using gas chromatography and mass spectroscopy (GC–MS). Our dataset could provide new insights into how taxonomic composition and biochemical quality of the planktonic food chains change with the environmental conditions in subarctic marine ecosystems.We analyzed the taxonomic and fatty-acid (FA) compositions of phytoplankton and zooplankton, and the environmental conditions at three coastal and offshore stations of the northern Baltic Sea. Plankton samples for FA analyses were collected under the framework of sampling campaigns of the Swedish National Marine Monitoring program in September 2017. Monitoring data of phytoplankton and zooplankton biomass, and environmental variables at each station were extracted from the Swedish Meteorological and Hydrological Institute database ( These FA ratios in zooplankton are potential indicators of marine environmental changes.The data on the ratios between essential polyunsaturated FA and non-essential monounsaturated FA in zooplankton  collected from the sampling stations in July-September 2017. Chrysophytes, cryptophytes, dinophytes, and euglenophytes are rich in docosahexaenoic acid (DHA), while diatoms are rich in eicosapentaenoic acid (EPA) according to −2) and relative zooplankton biomass at the sampling stations in September 2017.The raw data of FA compositions of seston and zooplankton are available at 22.1In August-September 2017, three stations  in the northern Baltic Sea were sampled to understand the impact of increased terrestrial organic matter on the nutritional quality in planktonic food chains. Station A5  is located in the Bothnian Bay, while station B3  and C14  are in the Bothnian Sea .Fig 1SamWe collected seston and zooplankton samples for FA analysis following the HELCOM guidelines during the sampling campaigns of the Swedish National Marine Monitoring program Eurytemora affinis  (Copepoda: Temoridae) Acartia sp. (Copepoda: Acartiidae) and cladocerans  (Phyllopoda: Bosminidae)), because of their wide distribution in the Baltic Sea and their differences in essential FA requirement Zooplankton were collected by using four vertical net hauls of the whole water column with a WP2 plankton net of 90 µm mesh size. Sampling was conducted in August-September 2017 (summer) which is the major growth season of zooplankton. Collected zooplankton were starved for at least 16 h in filtered (0.2 µm) natural seawater at 4°C in dark to empty their gut content. Subsequently, mesozooplankton was sorted according to taxa. We particularly selected three zooplankton taxa, i.e., 2.229-pentadecanoic acid  was used as the internal standard. Methylation of the samples was done by using 1:17:83 (v:v:v) trimethylsilyldiazomethane:isopropanol:dichloromethane.The FA composition of seston and zooplankton was analyzed following a modified method as described in We quantified the concentrations of FA methyl esters in the samples by using a gas chromatography-mass spectrometry  installed with a DB-5 capillary column . Splitless injection of 1 μl was used for each sample. Detailed inlet and oven temperature programs are reported in 2.3The environmental conditions as well as phytoplankton and zooplankton community compositions and biomass were monthly measured at the sampling sites following the HELCOM guidelines from January to October 2017 Measurements were averaged over depth, i.e. from 0 m to 10 m below water surface. DOC and humic substances concentrations were used to indicate the browning level of seawater, as DOC is a measure of colored and non-colored dissolved organic carbon, whereas humic substances are a measure of the colored fraction of dissolved and particulate organic matter.Depth-integrated water samples for phytoplankton analyses were collected from 0 to 10 m depth below the water surface using a vertical hose, and preserved in acidic Lugol solution (2%). Samples were settled for 24–48 h and counted using the inverted microscope method Zooplankton for community composition and biomass measurements were sampled from the whole water column with vertical net hauls from 5 m above the bottom with a WP2 plankton net of 90 µm mesh size. The samples were preserved in 4% formaldehyde solution and sub-sampled with Stempel-pipette before identification using a stereomicroscope. The wet weight for the different taxonomic groups and developmental stages were calculated according to https://sharkweb.smhi.se/.All of these data are available at the Swedish National Marine Monitoring program database at -3) of phytoplankton were aggregated at the class level. The phytoplankton classes included chrysophytes, cryptophytes, dinoflagellates, diatoms, euglenophytes, and cyanobacteria. Similarly, the biomass data of individual zooplankton species were collected in September 2017 and aggregated into the following taxa: Acartia sp., Eurytemora affinis, cladocerans, Limnocalanus macrurus, and other copepods.Zooplankton accumulate fatty acids in their active growth season, i.e. summer. Therefore, we used phytoplankton data of our study stations from July-September 2017. At each station, the monthly biomass data (µg C mThere is no ethical issue for this study as no animals or patients were involved in data acquisition.Tharindu Bandara: Data curation, Visualization, Investigation, Writing – original draft. Sonia Brugel: Data curation, Methodology, Investigation, Writing – review & editing. Agneta Andersson: Conceptualization, Methodology, Writing – review & editing, Supervision. Danny Chun Pong Lau: Conceptualization, Methodology, Investigation, Writing – review & editing, Supervision.The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.