Furthermore, BS significantly increased Pgc-1α and Ucp1 mRNA expression levels in epididymal adipose tissue, indicating thermogenesis is the key mechanism of BS. Taken together, our findings suggest that both soybeans prevent high-fat diet-induced obesity in mice by regulating lipid metabolism, and BS, in particular, has a greater antiobesity potential than YS.To evaluate the antiobesity effects of yellow and black soybean, C57BL/6 mice were provided with a normal diet, high-fat diet, HFD-containing yellow soybean powder (YS), and black soybean powder (BS) for six weeks. Compared with the HFD group, both YS and BS decreased body weight by 30.1% and 37.2% and fat in tissue by 33.3% and 55.8%, respectively. Simultaneously, both soybeans significantly reduced the serum triglyceride and total cholesterol levels and regulated the lipogenic mRNA expressions of Ppar Obesity, defined as a state of excessive fat accumulation, is a major public health issue with over 2.2 billion people worldwide being overweight or obese . ObesityCurrently, various medicines, such as orlistat, lorcaserin, and sibutramine, have been used to treat obesity by controlling appetite, lipid absorption, hormone action, and lipid metabolism . NeverthSoybean (Glycine max) has been widely consumed in Asian countries. Soybeans contain a high amount of protein, carbohydrates, dietary fiber, vitamins and minerals, and phytochemicals, including isoflavones , saponins, phenolic acids, and anthocyanin . Due to n = 10): normal diet (ND), high-fat diet (HFD), HFD mixed with yellow soybean powder (YS), and HFD mixed with black soybean powder (BS). Yellow soybean  and black soybean  were obtained from the National Institute of Crop Science . The ND group was fed with a normal diet . Other groups were fed with a high-fat diet   and its modification. For YS and BS groups, a high-fat diet was formulated with 50% (w/w) of each soybean powder and adjusted using the proximate composition of yellow and black soybean powder with protein (39.4% and 40.7%), carbohydrates (25.5% and 25.2%), and fat contents (18.9% and 17.8%), respectively. The mixture percentage of soybean was determined by the previous studies [Four-week-old male C57BL/6 mice were purchased from Koatech . The mice were housed in a controlled condition . The mice were given free access to food and water. The animals were acclimatized for one week and divided into four groups  was calculated as the ratio of body weight gain to the total food intake (FER = body weight gain (g)/food intake (g) × 100).At the end of the experimental period, the mice were fasted for 12 h and anesthetized with a mixture of 10 mg/kg bw of xylazine  and 100 mg/kg bw of ketamine . The fat in tissue (%) and lean mass (%) were measured using dual-energy X-ray absorptiometry . The lean mass (%) was calculated as the ratio of lean mass to body weight. The liver and epididymal adipose tissue were immediately isolated, weighed, and stored at −80°C for further analysis.Blood was collected from the retro-orbital plexus and immediately centrifuged at 3,000 × g for 15 min to obtain a serum. In addition, the liver function indicators such as aspartate transaminase (AST) and alanine transaminase (ALT) in the serum were measured using a commercial kit  following the manufacturer's instructions. The serum triglyceride (TG) and total cholesterol (TC) were analyzed by the automatic blood biochemical analyzer .μL of the sample mixed with cDNA, primers, and SYBR green using the CFX96TM RT-PCR detection system . Each value was normalized to 36b4, and the differences in mRNA expression levels of the genes were calculated using the delta-delta threshold cycle method compared with the HFD group. The sequences of the primer used in this study are presented in The total RNA from the liver and epididymal adipose tissue was obtained using Trizol . The cDNA was synthesized with purified RNA using a Prime Script ™ RT reagent kit . The PCR amplification was performed with 2 p < 0.05 was considered to be statistically significant.All data are presented as the mean ± standard deviation. The statistical comparisons among the groups were performed one-way ANOVA with Tukey's post-hoc tests using the Prism 9 program . p < 0.05). Both soybean seeds dramatically decreased body weight, weight gain, and food efficiency ratio compared with the HFD group without alteration of food and energy intake (p < 0.05). Interestingly, the BS group showed lower body weight, weight gain, and feed efficiency ratio than those in the YS group (p < 0.05). Thus, the BS intake effectively prevented weight gain induced by a high-fat diet compared to YS.The growth performance of mice is presented in p < 0.05). Besides, lean mass (%) was significantly (p < 0.05) increased by 23.6% and 36.2% in YS and BS groups compared with the HFD group, respectively. The BS group, in particular, had significantly lower fat in tissue and higher lean mass than the YS group (p < 0.05).The DEXA analysis was performed to assess whether weight loss in soybean-fed groups was owing to fat loss . The YS p < 0.05). The liver and epididymal adipose tissue weights of the YS  and BS (970.2 mg and 543.1 mg) groups were remarkably lower compared with those of the HFD group (p < 0.05). Furthermore, the BS group showed significantly lower epididymal adipose tissue weight than the YS group, similar to the ND group (p < 0.05).The morphology and weights of liver and epididymal adipose tissue are shown in p < 0.05). The AST level was significantly reduced in the BS group and the ALT level decreased in both soybean groups compared with the HFD group (p < 0.05). Also, the triglyceride (TG) and total cholesterol (TC) levels in the HFD group were higher than those in the ND group (p < 0.05). Both YS and BS groups showed a significant decrement in TG and TC levels compared with the HFD group (p < 0.05). Overall, there were no significant differences in the blood biomarker profiles between the YS and BS groups.The hepatotoxicity index and lipid profiles in the serum are shown in γ, Srebp-1c, Acc, and Fas, which are transcription factors and enzymes involved in de novo lipogenesis. Compared with the ND group, the HFD group significantly upregulated Pparγ, Acc, and Fas (p < 0.05). The YS and BS groups showed remarkably decreased expression levels of Pparγ, Acc, and Fas compared with the HFD group (p < 0.05). Otherwise, Srebp-1c expression levels were not significantly different among all groups. Overall, there were no differences in mRNA expression levels of lipogenic genes between the YS and BS groups. Interestingly, Pgc-1α and Ucp1 mRNA expression levels related to thermogenesis were significantly (p < 0.05) increased in the BS group compared with those of the HFD group; however, Pgc-1α and Ucp1 mRNA expression levels were not significantly altered in the YS group.To explore the mechanism underlying the antiobesity effects of YS and BS, the mRNA expression level of hepatic lipogenesis associated genes in the liver  and therIn this study, the authors assessed the effects of YS and BS on adiposity, biochemical parameters, and the regulation of hepatic and adipose tissue gene expressions in mice. The current study demonstrated that the YS and BS groups had reduced adiposity and improved blood biochemical parameters related to hepatotoxicity and lipid profiles. In total, these data demonstrated that both soybeans' consumption can prevent HFD-induced obesity in mice.Interestingly, the BS group was more effective in preventing HFD-induced obesity than the YS group. BS significantly decreased body weight gain, FER, fat in tissue (%), and epididymal adipose tissue, and it increased lean mass (%) compared with YS. BS has been reported to have various health-promoting effects due to its high contents of polyphenols such as anthocyanin, soyasaponin, and isoflavones. According to previous studies, black soybean seed coat contains high contents of anthocyanin  compared with yellow soybean , 21. In γ and Srebp-1c [γ induces the expression of genes such as Fabp4, which controls fatty acid uptake and TG synthesis in the liver. Srebp-1c also regulates the genes such as Acc and Fas that control fatty acid and TG synthesis. The current study shows that supplementation with both soybeans significantly decreased the liver weight and serum ALT, TG, and TC levels. Moreover, both soybeans suppressed the mRNA expression levels of Pparγ, Acc, and Fas, supporting reduced body adiposity. These results are associated with a previous study reporting that dietary soy protein is effective in reducing the activities of hepatic lipogenic enzymes and inhibiting the hepatic fatty acid synthesis in rats [β-conglycinin attenuates fatty liver and hyperlipidemia caused by a high-fat or high-cholesterol diet in mice and rats [β-conglycinin also lowered liver weight and serum TG through a decrease of fatty acid synthase activity and an augment of fecal TG excretion in KKAy mice [Obesity is associated with lipid metabolism abnormality since fatty acids from high-fat intake enter the liver to synthesize TG, which can lead to fatty liver and hyperlipidemia. Consumption of large quantities of HFD results in fat accumulation in the liver, thereby damaging it and potentially exposing it to nonalcoholic fatty liver disease , 27. HepSrebp-1c , 29. Ppa in rats . In partand rats –33. Soy KAy mice . HoweverKAy mice –37. Takeα, a coactivator of Pparγ, has been identified that stimulates mitochondrial biogenesis and cellular respiration by elevating the expression of Ucp1 [α and Ucp1 mRNA expression in adipose tissue, resulting in decreased energy expenditure and increased diet-induced obesity. Notably, we found that BS significantly up-regulated Pgc-1α and Ucp1 mRNA expression level, indicating thermogenesis is one of the key anti-obesity mechanism of BS. These findings were consistent with the previous reports that black soybean seed coats up-regulated Pgc-1α and Ucp1 in adipose tissue [Recently, the browning of the white adipose tissue has been suggested to be promising strategy for preventing or treating obesity in that it increases energy expenditure by heat production . Ucp1 is of Ucp1 . The HFDe tissue , 43. Adde tissue . Taken tIn conclusion, our study demonstrated that both soybeans prevented HFD-induced obesity and improved its related parameters in mice, but overall antiobesity effects of BS were stronger than YS. Mechanism studies have shown that both soybeans decreased lipogenic mRNA expression, supporting reduced body adiposity. In addition, BS promoted the mRNA expressions related to thermogenesis in epididymal adipose tissue, indicating that thermogenesis is the one of the key mechanism of BS. Taken together, these results suggest that both soybeans prevent HFD-induced obesity and BS exerts powerful antiobesity effects compared with YS. Furthermore, this study could be important to greatly expand our understanding of the nutraceutical potential of soybean.


Different types of grafts can be used for anterior cruciate ligament reconstruction (ACLR). There is little published data regarding skeletally immature patients. The purpose of this systematic review was to assess the clinical outcomes and complications for different autograft types used in all-epiphyseal, transphyseal and partial epiphyseal/hybrid ACLR in skeletally immature children and adolescents.PubMed, Embase and Cochrane databases were systematically searched for literature regarding ACLR using hamstrings, quadriceps or bone-patellar-tendon-bone (BPTB) autografts in skeletally immature patients. Studies were included if they examined at least one of the following outcomes: graft failure, return to sport(s), growth disturbance, arthrofibrosis or patient reported outcomes and had a minimum follow-up of 1 year. Case reports, conference abstracts and studies examining allografts and extra-articular or over-the-top ACL reconstruction techniques were excluded. Graft failure rates were pooled for each graft type using the quality effects model of MetaXL. A qualitative synthesis of secondary outcomes was performed.The database search identified 242 studies. In total 31 studies were included in this review, comprising of 1358 patients. Most patients (81%) were treated using hamstring autograft. The most common used surgical technique was transphyseal. The weighted, pooled failure rate for each graft type was 12% for hamstring tendon autografts, 8% for quadriceps tendon autografts and 6% for BPTB autografts. Confidence intervals were overlapping. The variability in time to graft failure was high. The qualitative analysis of the secondary outcomes showed similar results with good clinical outcomes and low complication rates across all graft types.Based on this review it is not possible to determine a superior graft type for ACLR in skeletally immature. Of the included studies, the most common graft type used was the hamstring tendon. Overall, graft failure rates are low, and most studies show good clinical outcomes with high return to sports rates.The online version contains supplementary material available at 10.1186/s12891-023-06749-4. The incidence of anterior cruciate ligament (ACL) ruptures in children is increasing, as well as the number of ACL reconstructions (ACLR) and graft failures in this age group , 67, 69.The most commonly used autograft types are hamstring, quadriceps and patellar tendon grafts , 70. PreThere is little published data on clinical outcomes of different graft types in children and adolescents with open physes . Common The aim of this systematic review is to assess the clinical outcomes and complications for different autograft types used in all-epiphyseal, transphyseal and partial epiphyseal/hybrid anterior cruciate ligament reconstructions in skeletally immature children and adolescents, in order to provide the surgeon with sufficient information when choosing a graft type and to stimulate personalized medicine. In line with findings in the adult population , 53, 54,This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines  and regiPubmed, Embase and Cochrane were searched from inception to December 20, 2021. The specific search strategy was created by a consultant with expertise in systematic review searching. A literature search using medical subject headings (MeSH) and text words related to ACL graft reconstruction in children/adolescents with open physes was used. Key search terms included skeletally immature children/adolescents, open growth plates, open physes, anterior cruciate ligament reconstruction, transphyseal, all-epiphyseal, partial epiphyseal/hybrid, physeal sparing technique, quadriceps, patellar tendon, bone patellar bone, graft type, autograft, hamstring, re-ruptures, graft failure, return to sport(s), growth disturbances, arthrofibrosis. The full search is described in Appendix All studies were screened by title and abstract and in a second phase using full text by two independent reviewers using the Rayyan software program . DisagreData extraction was performed by two independent reviewers and recorded into a spreadsheet. After comparison and discussion of both spreadsheets, a database containing the final extracted data was formed. Study characteristics recorded included authors, publication year, design, inclusion and exclusion criteria, bone age analysis or tanner staging, outcome measurements, number of study subjects, graft type, ACLR technique and rehabilitation program. Specific patient characteristics concerning mean age of study subjects, sex, body mass index (BMI) and timing of surgery were also recorded.Risk of bias was assessed with the Methodological Index for Non-Randomized Studies (MINORS) score . Each meThe primary outcome was graft failure, determined by Magnetic Resonance Imaging (MRI), arthroscopy and/or clinical diagnosis. Secondary outcomes were clinical outcomes and growth disturbances. The following clinical outcome measurements were included in the review: Knee stability, arthrofibrosis, growth disturbances, patient reported outcome measures (PROMs) and return to sports (RTS). The definition of arthrofibrosis varied per study and was usually measured through physical examination . PreviouGraft failure rates (primary outcome) were pooled for each graft type using the quality effects model of MetaXL . This moThe database search identified 242 studies. After the removal of duplicates, screening of abstracts and full texts, 31 studies were included in this review  investigated ACLR using hamstring tendon autograft . BPTB and quadriceps tendon autografts were used in respectively, 5 and 5 studies covering 141 and 103 patients. Although not specified in all studies, across all three graft types most studies used a transphyseal surgical technique. To a lesser extent a partial epiphyseal/hybrid or all-epiphyseal technique was applied  mm side to side difference. In the BPTB group, two studies reported KT-1000 scores of 2.1 ± 1.2 mm and 3.3 ± 1.6 mm. McCarroll et al. (1994) reported a < 3.5 mm side to side difference in 51 patients, whereas 6 patients had a 4–5 mm difference  in the hamstring group, 7 studies reported no ROM deficit. Anderson et al. 2003) reported a flexion deficit with a mean of 3° in 5 patients (42%), but no greater than 8°. Koch et al. (2014) reported a slightly reduced flexion of 5°–10° in 4 patients (33%). In the quadriceps group, only Gebhard et al. (2006) reported a loss in ROM in 2 patients (5%)  reported 3 cases (5% of the study population) of arthrofibrosis 11 to 16 weeks postoperative. Nelson et al. (2016) reported 4 cases (1%) and Redler et al. (2012) confirmed there were no cases of arthrofibrosis. The definition of arthrofibrosis in all three studies was unclear. Additionally, in the BPTB group, McCarroll et al. (1994) reported 2 cases of arthrofibrosis (3%) and defined arthrofibrosis as > 5° extension loss compared with the non-operated knee.In total 20 studies in the hamstring group, 4 in the quadriceps group and 2 in the BPTB group identified growth disturbances as an outcome measurement using radiographs. Two studies  were exIn the hamstrings group, 8 studies reported no occurrence of length discrepancy, 13 studies no valgus, and 16 no varus or recurvatum deformity. Length discrepancy occurred in 10 studies ranging from a 1.2 to 22 mm difference compared to the other leg in 124 patients in total. Valgus deformity was reported by 6 studies, ranging from 0.46° to 4.5° in 64 patients in total. Varus deformity was reported by only 2 studies. Koch et al. (2014) reported one patient with a 1.5° varus deformity and Faunø et al. (2016) reported 23 patients with a varus deformity ≥ 2° on the operated knee, which was statistically significant compared to the non-operated knee (p = < 0.01). None of the studies reported the occurrence of a recurvatum deformity  reported one patient with valgus deformity, Gebhard et al. (2006) reported no length discrepancies and Pennock et al. (2019) reported no length discrepancies as well as no angular deformities. Kohl et al. 2014) reported a mean length discrepancy of − 2.9 ± 8.6 mm (99.7 ± 0.9%) over all 15 patients compared to the other side with 2 patients > 10 mm and one patient with valgus deformity. Both Memeo et al. (2012) and Shelbourne et al. (2004) reported no growth disturbances in the BPTB group IKDC was reported by 16 studies, average scores ranged from 85.6 to 96.5. The Lysholm score was reported by 14 studies, ranging from 58.8 to 97.9. Nine studies used the Tegner score, showing results ranging from 4.9 to 8.6. Faunø et al. (2016) and Razi et al. (2019) reported a mean KOOS of 76.8 ± 15.1 and 75 ± 7.4, respectively. Cordasco et al. (2016) and Graziano et al. (2017) both reported the Marx Activity Rating Scale with mean values of 13.4 ± 3.6 and 23.2 ± 8.3, respectively , Kohl et al. (2014) and Pennock et al. (2019) reported a mean Lysholm score of 94.3 range 53–100), 94.0 (range 68–100) and 96 ± 8, respectively. Gebhard et al. (2006) and Pennock et al. (2019) also reported a mean Tegner score of 5.9 and 6.6, respectively  also compared the Lysholm and Tegner scores of the quadriceps group directly to the hamstring group, showing no statistically significant differences .In the BPTB group, only Shelbourne et al. (2004) reported a mean IKDC score of 95.4 ± 6.9  as an outcome measurement. Most studies recorded the percentage of patients who returned to the same level or higher level of sports or activity as before the operation ranged. These percentages ranged from 63 to 100% in the hamstrings group (n = 15) and 92–100% in the BPTB group. No studies in the quadriceps group identified RTS as an outcome measurement. Five studies in the hamstring group reported the time to RTS, with means ranging from 7 to 13.5 months. In the BPTB group, only McCarroll et al. (1994) reported a time to RTS ranging from 1 to 9 seasons of competition , quadriceps tendon 8% (95%-CI: 2-18%) and BPTB 6% (95%-CI: 1-13%). There were no statistically significant differences in graft failure rates between the three graft types based on comparison of the 95%-confidence intervals. The variability in time to graft failure was high. According to the available literature in this systematic review, no graft seems therefore to be evidently superior in graft failure rates in transphyseal, all-epiphyseal or hybrid ACL reconstruction techniques. Overall, there are no large differences in graft failure rates, however there is a tendency towards higher failure rates in hamstring tendon autografts. This tendency is supported by the only study in this review that directly compared hamstring autografts to quadriceps autografts, showing a statistically significant lower graft failure rate when using a quadriceps tendon autograft . A systeCompared to previous systematic reviews on outcomes after ACLR in skeletally immatures, graft failure rates were somewhat higher in the current study , 38, 70.One of the secondary outcomes of interest were growth disturbances. After ACL reconstruction, growth disturbances can occur in about 2.6–24% of the cases , 38. In Another secondary outcome of interest was return to sports. The RTS percentages were high in most studies, with only two studies scoring lower than 80% , 45. IntThe other secondary outcomes of interest could also not be quantitatively compared between different graft types, due to limited number of studies evaluating a specific outcome or due to the use of different outcome measures. In all graft groups, clinical evaluation showed limited residual loss of range of motion and instability in the KT-1000 arthrometer or during Lachman or Pivot shift test. Different knee-specific and physical activity PROMs were analyzed in the included studies, which showed similar outcomes in the graft groups. Mostly adult versions of PROMS were used, while these are often not appropriate for a pediatric population .A limitation of this systematic review is that it focused only on clinical outcomes of graft types in ACL reconstruction techniques in skeletally immature patients. Other outcomes, such as incorporation, ligamentalization and mechanical properties of the different graft types were not included. These processes are relevant in relation to the structural properties of a graft . As suchAnother limitation is the methodological quality of the included studies. Since almost all studies are cohort studies or case series, the level of evidence is low. The MINORS tool used to determine the quality of the studies also showed moderate quality. The most common factors which increased the risk of bias were an unbiased (blinded) assessment of the study endpoints and failing to prospectively calculate a sample size. The different graft types could not be compared directly due to variations in outcomes and surgical techniques and due to the small sample sizes of the quadriceps and BPTB groups. The strength of this systematic review is however that it provides a current overview of the outcomes of different graft types used in skeletally immature patients. The investigated groups in the individual studies were grossly comparable regarding surgical indications, study designs and follow-up duration.Future research should focus on the clinical outcomes and complications of using a quadriceps or BPTB autograft directly compared to a hamstring autograft. Another field of interest might be extra-articular surgical techniques such as the ‘’over-the-top ACL reconstruction or additional lateral extra-articular tenodesis (LET). ACLR in immature patients following these techniques also showed promising functional results in terms of return to sports and graft survival rate . The use of a registry such as the ESSKA Paediatric Anterior Cruciate Ligament Initiative (PAMI) registry might provide an opportunity to investigate a large number of patients . AdditioBased on this review it is not possible to determine a superior graft type for ACLR in skeletally immature. Of the included studies, the most common graft type used was the hamstring tendon. Overall, graft failure rates are low, and most studies show good clinical outcomes with high return to sports rates.Below is the link to the electronic supplementary material.Appendix 1: Draft Pubmed search. Appendix 2. Study quality and study bias scoring of the 30 included studies using the MINORS score for nonrandomized studies


Na), urine specific gravity (USG), fractional excretion of sodium (FENa), fractional excretion of urea (FEUrea), urine osmolality (UOsm), urine to plasma creatinine ratio (UCr/PCr) and renal failure index (RFI). Overall, 431 patients were included. UNa, UOsm, USG and RFI showed high specificity > 85% for prerenal AKI, UNa and RFI provided good specificity for ATN. Loop diuretics, ACE inhibitors/AT1 blockers or pre-existing chronic kidney disease had no impact. In patients with AKI, UNa, USG and RFI: (1) proved to be very specific for prerenal AKI and showed high sensitivity for ATN; (2) can be easily determined using serum and spot urine; and (3) are not confounded by medication or comorbidities. These parameters/indices are helpful to identify the aetiology of AKI and to guide therapy, thereby improving patients’ safety and outcome.Acute kidney injury (AKI) is very common in hospitalized patients, affecting patient’s mortality and morbidity. Major causes are prerenal AKI and acute tubular necrosis (ATN). Even though a variety of parameters/indices exist, their reliability and practicability are controversial: in fact, there is a need for a simple diagnostic approach for AKI in in-patients with parameters easily obtained in any hospital. The objective of the study was: (1) to assess reliability of simple laboratory parameters/indices to differentiate pre-/intrarenal AKI; (2) to evaluate the most reliable and feasible parameters/indices; and (3) to identify the possible impact of confounding factors. Retrospectively, in-patients with AKI hospitalized in 2020 in a university nephrology department were included. Spot urine and 24-h collection urine was analyzed with urine sodium (UThe online version contains supplementary material available at 10.1007/s11739-023-03365-x. Acute kidney injury (AKI) is one of the most common diagnoses in hospitalized patients and has relevant impact on morbidity and mortality . AKI is In recent years, new laboratory parameters and biomarkers have been proposed to foster establishing an accurate diagnosis in the case of impaired kidney function, and attempts have been made for using them to predict kidney recovery –9. In hoThe objective of the present study was: (1) to assess reliability of simple laboratory parameters and indices to differentiate pre- and intrarenal causes; (2) to evaluate the most reliable and feasible parameters and indices; and (3) to identify the possible impact of confounding factors on the diagnostic workup, such as comorbidities, pre-existing chronic kidney disease and medication. Overall, the study should help to guide therapy in patients with AKI until a nephrological co-assessment can be provided, thereby improving patient safety and outcome.In this retrospective cross-sectional, descriptive study at nephrology ward at the University Hospital in Marburg, Germany, in-patients with an established diagnosis of AKI as indicated in the discharge letter between January 1st, 2020, and December 31st, 2020, were identified. Exclusion criteria were age < 18 years and patients with a functional renal transplant. AKI was defined according to AKIN criteria, using serum creatinine and urine output. At time of presentation, the cause of AKI was suggested by the nephrologist in charge. Patients with obstructive nephropathy as determined by ultrasound were transferred to urological services and excluded. Medical history, clinical signs and symptoms, imaging as well as laboratory parameters were regularly used to assess volume status and to identify the most likely reason for AKI based on routine nephrology care and clinical experience. The complex diagnostical approach included differentiated proteinuria analysis, measurement of urinary concentration of electrolytes, creatinine, and osmolality in spot urine or/and 24 h collection urine, and serum parameters to differentiate acute and chronic components of kidney injury. A final diagnosis of prerenal or intrarenal AKI was established to the nephrologists’ discretion by considering the development of diuresis, laboratory values and the clinical course.Schrier et al. (Na), fractional excretion of urea (FEUrea), urine osmolality (UOsm), urine to plasma creatinine ratio (UCr/PCr) and renal failure index as potential markers and indices to differentiate between pre- and intrarenal causes of AKI .Data were analyzed using SPSS statistics (version 28) and Excel (version 16.0). Linear and Phi correlation was performed between urine parameters and the underlying cause of kidney injury, and sensitivity, specificity, positive and negative predictive values (PPV and NPV) as well as positive likelihood ratio were calculated for prerenal AKI and ATN. Data are presented as mean ± standard deviation, unless otherwise stated; where applicable, the confidence interval (CI) is shown. A n = 210, 48.7%). Prerenal causes were the most common reasons for renal failure , while ATN was the predominant reason for loss of kidney function in intrarenal AKI . In 41 cases (9.5%), a combination of multiple reasons was present, mainly a combination of ATN with a pre- or postrenal component. At date of admission, 40.2% of patients had pre-existing CKD, predominantly in advanced stages.A total of 431 patients were included in the study. Of those, 118 patients were transferred from other departments in the hospital 27.4%), about a quarter of patients included in the study were treated on the ICU at some point. Mean age was 71.6 ± 14.6 years at time of admission with a male predominance (63.3%). Baseline characteristics of all patients are shown in Table 7.4%, abon = 74; intermittent RRT, n = 33; peritoneal dialysis, n = 2); more than half of those (62 patients = 56.8%) required permanent RRT at time of discharge . Seventy-eight patients (18%) deceased, while six patients (1.4%) were discharged to a palliative setting. At discharge, 191 patients (44.3%) still had impaired renal function with elevated creatinine levels, meeting criteria of acute kidney disease (AKD), which is defined as a persistent reduction of kidney function between 7 and 90 days following AKI  was performed in 109 patients  received an extended blood and urine diagnostic workup, including collective urine over 24 h and cystatin-C as an alternative marker for glomerular filtration with advantages in the creatinine-blind range. In 87 patients, diagnostic workup was delayed; in 13 patients, collection of 24-h urine wasn’t feasible due to incontinence and refusal of a Foley catheter. In those cases, measurement of electrolytes and determination of proteinuria was performed using spot urine. In the remaining patients, the diagnostic workup was delayed, mainly due to clinical focus on non-renal diseases.r = 0.661, p < 0.001). At time of admission, 114 patients (34.4%) showed a FENa below 1%, matching the nephrologists’ diagnosis of prerenal AKI in 83.3% cases (n = 95). In fact, there was a significant correlation of FENa < 1% and prerenal AKI . Reliability of FENa was assessed by logistic regression analysis, revealing a sensitivity of 91.4% and specificity of 36.1% for FENa to predict prerenal AKI. Assessment of urinary sodium concentration was used to help in differentiating between pre- and intrarenal causes, showing a significant correlation of UNa < 30 mmol/l with prerenal AKI  but not with intrarenal AKI , when UNa ≥ 30 mmol/l was used. Of note, FENa > 1% was not correlated with intrarenal AKI ; similarly, fractional excretion of urea (FEUrea) < 35% was not helpful to suggest pre- or intrarenal cause of AKI. In fact, FEUrea showed the lowest sensitivity and specificity of all parameters. Of note, specificity of the renal failure index (RFI) < 1 was surprisingly high (85.7%) for prerenal AKI, while an RFI > 1 was very sensitive for an intrarenal cause . While specific gravity in spot urine was helpful to identify intrarenal disease, this parameter showed no correlation with urine osmolality in 24-h urine . Regarding the extended proteinuria diagnostic in 24-h urine, an increased concentration of α1-microglobuline in 24-h urine was indicative for ATN with remarkable sensitivity (92%).Screening for proteinuria via spot urine was positive in 252 cases (58.5%), half of these patients presented with pre-existing glomerular damage and CKD  and urine osmolality are also often promoted as helpful means  data collection was performed in a nephrology department with a potential higher prevalence of patients with pre-existing renal diseases, thereby not reflecting in-patients of other departments. On the other hand, in the present setting, a comprehensive serological and urine diagnostic was guaranteed, allowing ideal conditions for evaluating renal indices and parameters and their reliability under different circumstances; (2) the retrospective study design per se has limitations, since data are incomplete, e.g., due to missing follow-up; and (3) although the cause of AKI was established according to the nephrologists’ judgment, there was no second evaluation.Na, USG and RFI have the highest specificity to identify prerenal AKI and the best sensitivity for intrarenal AKI; (2) loop diuretics, ACE-inhibitors and AT1- blockers seem to have no significant impact on these parameters/indices; and (3) UNa, USG and RFI can be measured easily, quick and cost saving using spot urine and serum. These simple tools provide a practicable and quick diagnostic approach for non-nephrologists to differentiate pre- and intrarenal AKI, thereby allowing an early specific therapy and subsequently improving patients’ safety and outcome. However, further prospective studies are needed to evaluate the reliability of this recommendations in clinical practice as a proof of concept.In conclusion, we showed that in hospital-acquired AKI: (1) many indices to differentiate are available, but USupplementary file1 (DOCX 43 KB)Below is the link to the electronic supplementary material.


Plasmodium falciparum. Candidates were validated in plasma samples from a cohort of pediatric patients with malaria from Mozambique, resulting in the identification of several markers with capacity to distinguish uncomplicated from severe malaria, the most potent being the metallopeptidase ADAMTS18. Two other biomarkers, Angiopoietin-like-4 and Inhibin-βE were able to differentiate children with cerebral malaria within the severe malaria group, showing increased sensitivity after combination in a biomarker signature. The validation of the predicted candidate biomarkers in plasma of children with severe and cerebral malaria underscores the power of this transcriptomic approach and indicates that a specific endothelial response to P. falciparum–infected erythrocytes is linked to the pathophysiology of severe malaria. Malaria can quickly progress from an uncomplicated infection into a life-threatening severe disease. However, the unspecificity of early symptoms often makes it difficult to identify patients at high risk of developing severe disease. Additionally, one of the most feared malaria complications — cerebral malaria — is challenging to diagnose, often resulting in treatment delays that can lead to adverse outcomes. To identify candidate biomarkers for the prognosis and/or diagnosis of severe and cerebral malaria, we have analyzed the transcriptomic response of human brain microvascular endothelial cells to erythrocytes infected with   Plasmodium falciparum, uncomplicated malaria (UM) may rapidly progress into severe malaria (SM), which is associated with different complications, including cerebral malaria (CM). This is one of its most feared complications, with a high risk of death (18%–30%), and is also associated with long-term cognitive and neurological deficits in up to 30%–50% of survivors , the protein commonly used in RDTs, have evidenced high percentages of false-negative P. falciparum diagnoses in some endemic areas  , resulted in the identification of 3 potentially novel candidate biomarkers for pediatric SM: ADAM metallopeptidase with thrombospondin type 1 motif 18 (ADAMTS18), Angiopoietin-like-4 (ANGPTL4), and Inhibin-βE (INHBE). Furthermore, 2 of them, ANGPTL4 and INHBE, are also able to significantly differentiate between pediatric CM and noncerebral SM.Here we have used this transcriptomic (RNA-Seq) analysis of human brain microvascular endothelial cells (HBMEC)  incubates (iRBC) , a systeP. falciparum, but not by inflammatory stimuli, that encode putative secretory proteins. After confirmation that the candidate proteins are secreted in response to P. falciparum in vitro, they were validated in a pediatric cohort of malaria patients with different degrees of severity , compared with control RBCL  (https://doi.org/10.1172/jci.insight.172845DS1).We have analyzed the transcriptome of HBMEC incubated with rol RBCL  to identrol RBCL , 25 and  < 0.05)   by iRBCL compared with TNF, a potent inflammatory stimulus that is highly induced during SM and was also included in the transcriptomic analysis  Supplem. Finally2 fold change = 0.48) (2 fold change = –0.49). We therefore investigated the secretory profile of Angiopoietin-2 in HBMEC to determine whether this marker is secreted in response to inflammatory stimuli, as previously described  , but it  = 0.48) , since iescribed , and/or um–iRBCL , and thiP. falciparum–iRBCL. For this purpose, we determined the levels of each candidate protein in the culture media between 1 and 24 hours after incubation of HBMEC with P. falciparum–iRBCL, using uninfected RBCL as a negative control. Out of the 14 candidates, 7 proteins were confirmed to be secreted by HBMEC in response to P. falciparum–iRBCL at the protein level (We next tested whether the proteins encoded by the selected candidate biomarker genes  are indein level . Seven cin level .n = 136) or diagnosed with UM and treated as outpatients (n = 128). Patients with SM include children with different complications (frequently more than 1 complication in a single patient): CM (n = 23), prostration (n = 96), multiple seizures (n = 60), severe anemia (n = 35), hypoglycemia (n = 10), or acidosis (n = 53). When children with CM presented more than 1 complication, they were classified in the CM group  of age admitted to Manhiça District Hospital in southern Mozambique with SM  for ADAMTS18; 0.68 (P < 0.0001) for ANGPTL4; and 0.63 (P = 0.0004) for INHBE. Moreover, we observed a significant correlation between ADAMTS18 and ANGPTL4 levels across the cohort . To a lesser extent, INHBE levels were also correlated with these biomarkers . As expected because of the correlation between them, the combination of these candidates into a single biomarker signature did not improve AUC.The levels of these candidate biomarkers were then tested in the entire cohort to compare the groups with UM versus SM. We observed significant differences in the levels of ADAMTS18, ANGPTL4, and INHBE between UM and SM , with anP. falciparum biomass, measured as levels of HRP-2, since malaria severity is strongly associated with this parameter , while ADAMTS18 had a weaker correlation , while INHBE was not significantly correlated. No correlation was found between any of the candidate biomarkers and circulating parasitemia determined by quantitative PCR (qPCR).We also determined the relation of the candidate biomarkers to arameter . We obseum–iRBCL , correlaWe also analyzed the relation of the candidate biomarkers with other malaria complications, finding a significant association of the 3 candidate biomarkers with neurological complications such as CM and prostration. ADAMTS18 and ANGPTL4 were also correlated with acidosis and severe anemia. Jaundice was only associated with ANGPTL4, and multiple seizures was associated with ADAMTS18 and INHBE .P < 0.005) and 0.70 (P < 0.002), respectively (P = 0.0574). Analysis of the correlation between the levels of ANGPTL4 and INHBE showed that these 2 candidate biomarkers were not significantly correlated among SM cases ; combining both biomarkers in a logistic regression model  resulted in a good model fit ; and using a LLR test showed that the ANGPTL4 + INHBE model was significantly better than the individual models . Collectively, these observations indicate that INHBE and ANGPTL4 are uncorrelated biomarkers and could serve as independent predictors, increasing the power when combined in a biomarker signature. A combined analysis of these 2 biomarkers selecting the highest relative value of each one (P < 0.0001).We next determined whether the candidate biomarkers could differentiate between children with CM within the group with SM. Further analysis of the 2 candidate biomarkers that were significantly associated with CM, ANGPTL4 and INHBE, showed an AUC of 0.68 , since the rupture and release of densely packed iRBC contents in close contact with endothelial cells is sufficient to cause loss of barrier integrity  transcription was upregulated in HBMEC by ignaling , 35.The previously characterized biomarkers for SM reach similar levels of sensitivity and specificity as the ones reported here, with Angiopoietin-2  at 5% hematocrit in RPMI 1640 (Corning) supplemented with 25 mM HEPES (Thermo Fisher Scientific), 25 mM sodium bicarbonate (MilliporeSigma), 0.5 mM hypoxanthine (MilliporeSigma), 0.5% Albumax II (Thermo Fisher Scientific), and 10 mg/mL gentamicin (Thermo Fisher Scientific) at 37°C in a gas mixture of 5% O2, 5% CO2, and 90% N2. Parasite cultures were synchronized using 5% sorbitol (MilliporeSigma). P. falciparum–iRBCs at the schizont stage were isolated from highly synchronous cultures using magnetic columns . Uninfected RBC lysates (RBCLs) or iRBCLs were generated by 10 freeze-thaw cycles using liquid nitrogen and a 37°C water bath.6 to 8 × 106 iRBCs/cm2, where 8 × 106 iRBCs/cm2 was estimated to be equivalent to 2 layers of iRBCs over the HBMEC monolayer .n = 120) and 2014 (n = 148). Samples were collected from children < 10 years of age diagnosed with clinical malaria , either outpatient diagnosed with UM (no further complications) or admitted to Manhiça District Hospital for SM. Cases of SM were defined as patients with a clinical diagnosis of malaria and an asexual P. falciparum parasitemia > 0 parasites/μL by microscopic examination of Giemsa-stained blood smears, and fulfilling at least 1 of the following criteria: CM (Blantyre Coma Score ≤ 2), severe anemia (packed cell volume < 15% or hemoglobin < 5 g/dL), acute respiratory distress (chest indrawing and/or deep breathing), acidosis , jaundice (bilirubin > 60 μmol/L), prostration (inability to sit or breastfeed in children old enough to do so), hypoglycemia (blood glucose < 2.2 mM), and multiple seizures (≥ 2 convulsions in the preceding 24 hours). Children with positive bacteremia were excluded. Children with SM were treated according to Mozambican national guidelines with parenteral quinine in 2006 or parenteral artesunate  in 2014, and those with UM were treated with a combination of oral amodiaquine and sulfadoxine-pyrimethamine  in 2006 or with artemether-lumefantrine  in 2014. Quantification of parasitemia was also performed by qPCR targeting the P. falciparum 18S rRNA gene  was compared between both studies, showing differences < 7% of the maximum value between both studies.Heparinized blood (10 mL) from study participants was collected and processed within 2 hours. After centrifugation at 200Power transformation on the values was performed. Based on this, the maximum value for each biomarker was selected for each patient and was used to calculate the signature. Analysis using Support Vector Classifiers, Logistic regression, and TabPFN classifier  methods P < 0.05 was considered significant. Differences in continuous variables were analyzed using the Mann-Whitney U test with Bonferonni correction to adjust for multiple testing. Differences in categorical variables were assessed using Fisher’s exact test or Pearson’s χ2 test, as appropriate.Statistical analyses were performed on Prism 9 (GraphPad Software). The Shapiro-Wilk test was used to test whether the data followed normal distribution. The specific statistical tests used are detailed in the figure legends. The exact statistical tests used are detailed in the figure legends, and Written informed consent was obtained from parents or guardians of study participants prior to participation. Ethical approval was granted by The National Mozambican Ethical Review Committee (Mozambique) and Hospital Clínic .The RNA-Seq data used in this manuscript were described before  and are CG, AR, MDF, and RV designed research studies; CG conducted experiments; AS, RB, and SM collected patient samples; RV, QB, and AM designed patient studies; CG, MDF, and AR analyzed data; and AR, CG, RV, MDF, and QB wrote the manuscript.


Heart failure (HF) is the only cardiovascular disease with an ever-increasing incidence.The aim of this study was to assess the predictors of adverse clinical events (CE) and the creation and evaluation of the prognostic value of a novel personalized scoring system in patients with HF.2/HR); and C, high sensitivity C-reactive protein (hs-CRP)) was created. The Kaplan–Meier method and log-rank test were used to compare the CE.The study included 113 HF patients (median age 64 years (IQR 58–69); 57.52% male). The new novel prognostic score named GLVC ; L, left ventricular diastolic diameter (LVDD); V, oxygen pulse (VO p = 0.002), high LVDD , low oxygen pulse , and high hs-CRP  were independent prognostic factors for adverse CE in HF population. All the patients were stratified into a low-risk or high-risk group according to a novel “GLVC” scoring system. The Kaplan–Meier analyses demonstrated that patients in the high-risk group were more predisposed to having higher adverse clinical events compared to patients in the low-risk group.Results from final analyses showed that low GLPS (< 13.9%, OR = 2.66, 95% CI = 1.01–4.30,A novel and comprehensive personalized “GLVC” scoring system is an easily available and effective tool for predicting the adverse outcomes in HF. Heart failure (HF) is a common health problem, affecting about 1–2% of adults in developed countries, while in people > 70 years of age, this proportion is > 10% . HF is oThere are many variables that inform about prognosis. The research carried out as part of this study will identify independent variables associated with poor prognosis of patients hospitalized for HF.The aim of the study was to identify independent variables associated with an unfavorable prognosis of patients hospitalized for heart failure based on an available in literature-specific predictive models and create a new prognostic personalized scoring system for the better predictive value for patients with HF.This is a preliminary study based on a small group. The study included 113 HF patients (median age 64 years (IQR 58–69); 57.52% male).According to the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure , HF withHFrEF patients with LVEF <  = 40% HFmrEF patients if LVEF 41–49% HFpEF patients if LVEF ≥ 50% Patients were divided into 3 subgroups:The study’s inclusion and exclusion criteria are defined in Table Every patient underwent a clinical assessment on admission. The following data were included in this analysis: baseline demographics, medical history, medication data, assessment of the severity of HF symptoms according to the NYHA classification , and phyIn all patients, the following diagnostic procedures were also performed during hospitalization: selected laboratory tests and concentration of selected biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, bioelectrical impedance body mass analysis, Doppler echocardiography, electrocardiogram (ECG), cardiopulmonary exercise test (CPET), and 6-min walk test (6MWT).One year after discharge, a telephone interview was conducted for the following events: death, cardiovascular adverse events , and hospitalization for HF. The quality of life according to the KCCQ questionnaire was also re-assessed during the telephone interview.Another hospitalization for HFHospitalization for cardiovascular reasons Death from any causeFor the clinical and diagnostic stratification, a 2D echocardiogram was performed in all of the 113 patients using a Vivid E95 system  with a 1.4–5.2 MHz matrix transducer and tissue Doppler imaging software. Body surface area (BSA) was obtained using DuBois and Dubois’ formula . The echStandard 12-lead electrocardiograms were recorded using MAC 5500 machines . Every ECG was recorded on admission. With the initial visual inspection, recordings with inadequate quality were excluded. The MAC 5500 machines measured the QRS duration from the beginning of the Q wave to the end of the S wave in all 12 leads. The MAC 5500 machines measured the QT interval from the onset of the QRS complex to the end of the T wave in all 12 leads. The averaged QT interval was then corrected for heart rate using the Bazett formula (QTc = QT/√RR).Bioelectrical impedance analysis (BIA) was performed with the body composition analyzer MC-780MA S , which performs 15 impedance measurements per patient, by measuring the conductance of electrical current across five body segments  at three frequencies each  . The folSymptom-limited CPET was performed on an electromagnetically braked upright cycle ergometer Bike M  with a metabolic gas analyzer METALYZER 3B  using The MetaSoft Studio application software of CORTEX systems. The system was calibrated with a standard gas mixture of known concentrations before each test. The breath gas analyzer was internally calibrated directly prior to each measurement. The volume of gases and the flow sensor were also calibrated directly prior to the test, validating the calibration twice a year.Maximum heart rate (HR) of 220 beats per minute minus years of age.Drop in HR during exercise.Drop in systolic blood pressure (SBP) of > 10 mmHg from baseline blood pressure despite an increase in workload.Signs of poor perfusion .ST segment depression (> 1.0 mm) or elevation (> 1.0 mm).Lack of ventilatory reserve.Respiratory exchange rate (RER) higher than 1.15.Plateau in consumption of oxygen, with an increase of less than 150 ml/min in about 30 s.Personal discomfort .Severe cardiac arrhythmia .After 5 min of rest on the cycle ergometer, exercise commenced at 50 W; then, the work rate was increased by 25 W every 3 min. During CPET, blood pressure was measured by a conventional sphygmomanometer Exacta  every 3 min. HR and standard 12-lead electrocardiogram (ECG) were monitored using an exercise electrocardiogram Meta control 3000  which connects the CORTEX METALYZER 3B. The criteria for discontinuation of CPET were as follows:Expired gases were continuously measured in all subjects on a breath-by-breath basis. Uptake of oxygen was measured in a breath-by-breath fashion, recording mean values over 30 s.Before, during, and after the test, we recorded continuously HR, breathing frequency, minute volume, uptake of oxygen, and elimination of carbon dioxide. Blood gas analyses were recorded at rest , at anaerobic threshold (AT), at the exercise peak (Peak), and at 90 s after the end of the effort.2) and oxygen production (VO2). A peak RER of > 1.10 was considered an indication of excellent subject effort during CPET.The RER was defined as the ratio between carbon dioxide production (VCO2 (VO2 max) was defined as the mean of values measured within the last 20 s of exercise and expressed as both ml/min and ml/kg/min (VO2 max/kg) and as the percentage of predicted peak oxygen consumption (VO2%Norm).Peak VO2).AT was determined by gas-exchange criteria as the point of nonlinear increase in ventilation equivalents for oxygen (ventilation starts to increase at a faster rate than VO2 slope), the slope of the increase in ventilation to the increase in CO2 output, was calculated during incremental exercise using least squares linear regression by the computer system METALYZER 3B.The minute ventilation/carbon dioxide production relation slope (VE/VCO2 pulse (VO2/HR) was defined by dividing VO2 by HR.O2%Norm at AT and Peak were calculated according to published age and sex-normalized values [VOd values .The walking tests were conducted according to the standardized protocol . PatientThe Kansas City Cardiomyopathy Questionnaire was used to assess the quality of life of the patients. It is a validated instrument to assess health status and quality of life among persons with HF. The self-administered questionnaire includes 23 items which quantify the importance of dyspnea, fatigue, and edema for physical, social, and emotional functions. Patients answer the questions as they related to the previous 2 weeks. An overall summary score can be derived from the physical function, symptom (frequency and severity), social function, and quality of life domains. For each domain, the validity, reproducibility, responsiveness, and interpretability have been independently established. Scores are transformed into a range of 0–100, in which higher scores reflect better health status .Approximately 10 ml of blood from a peripheral vein was collected into a tube containing potassium ethylenediamine tetra-acetic acid (1 mg/ml) for the determination of selected biomarkers. The samples were centrifuged at 4 °C for 20 min. The plasma was separated and subsequently frozen at − 70 °C until further analysis without undergoing any additional freeze–thaw cycles. Concentrations of biomarkers were measured by dedicated ELISA immunoassays.Statistical analysis was conducted using statistical packages STATISTICA PL 13.1.N) and the corresponding percentage (%).The Shapiro–Wilk test was used to check the normality of the statistical distribution. All variables with normal distribution were expressed as mean and standard deviation (SD). All variables with no normal distribution were expressed as median and interquartile range . Categorical variables were expressed as the number of observations  and 95% confidence interval (95% CI) were reported for each factor in multivariate analysis. Some factors identified as potentially significant by univariate analyses, based on literature data and own clinical experience, were entered into a multivariate analysis to determine the significant independent prognostic factors.The factors identified by the multivariate analysis were further used to establish a novel prognostic score. The optimal cut-off levels of continuous variables were expressed as median for the whole population.The quality of individual models and the usefulness of subsequent markers was assessed using ROC curves analysis . The area under the curve (AUC) of receiver operating characteristic (ROC) was used to identify the predictive accuracy of the new prognostic scoring system and its constituent parameters.Survival curves were calculated using the Kaplan–Meier method.p < 0.05.All statistical tests were 2-sided. Results were considered statistically significant when The tables present only variables which differ or are selected in the context of the article.2/HR (V), and hs-CRP (C) to create a novel “GLVC” prognostic score. The usefulness of subsequent markers was assessed using ROC curve analysis .According to the results of the univariate analysis, available literature data, and own clinical experience, we selected some significant variables for multivariate analysis. The significant factors identified by the subgroup step-back multivariate analysis, including hs-CRP, NTproBNP in the group of laboratory parameters; LVDD, GLPS, LVEF in the echocardiographic group; HR on admission, width of the QRS complex in the electrocardiographic group and oxygen pulse in the group of CPET parameters. After them, we selected four parameters based on literature data and our own clinical experience, including GLPS (G), LVDD (L), VOThis study was conducted in the Heart Failure Unit, Department of Cardiology and Congenital Heart Diseases of Adults in Polish Mother’s Memorial Hospital Research Institute, in a tertiary hospital in the city of Lodz, Poland.The ClinicalTrials.gov database is provided herein (No 36 NCT04753814).N = 113), the mean LVEF was 44% (IQR 39.0–50.0). Of those patients, 26% (N = 30) had HFpEF, 47% (N = 53) had HFmrEF, and 26% (N = 30) had HFrEF. Ischemic etiology of HF was present in 43.36% of all patients (N = 49). Of all patients with baseline rhythm data, 23 (20.35%) had AF, and 90 (79.65%) had SR in ECG on admission. The studied population was burdened with the most common comorbidities including arterial hypertension, coronary artery disease, diabetes mellitus, valve diseases, and hyperlipidemia. Detailed characteristics of the study population are presented in Table The median age of all patients was 64 years , and 57% (65) of these patients were male. Based on the available echocardiography results N = 11, the meap-value below 0.05) affecting composite adverse outcome occurrence in HF patients. According to the results of the univariate analysis, available literature data, and own clinical experience, we selected some significant variables for multivariate analysis. The selected multivariable analyses for each of the following areas, i.e., biochemical test, electrocardiographic, and cardio-pulmonary exercise results, were conducted. These three multivariable analyses selected the candidate markers including NTproBNP, hs-CRP, LVDD, GLPS, LVEF, and oxygen pulse for the total multivariable analysis. The results of the final multivariate analysis was presented in Table To determine the prognostic value of collected parameters of HF, clinical characteristics of the patients, ECG results, bioelectrical impedance body mass analysis results, echocardiography results, key CPET parameters, 6MWT results, and laboratory data, including NTproBNP, hs-cTnT, hemoglobin, sodium, potassium, creatinine, uric acid, and biomarkers including neprilysin, galectin-3, and hs-CRP, ST-2 were subjected to analyses. The univariate regression analysis Table  revealed2/HR (V), and hs-CRP (C), were used to create the personalized scoring system (GLVC). All of these selected parameters  have a significant influence on the adverse outcome, i.e., re-hospitalization or sudden death.Based on literature data and our own clinical experience, the four following markers, i.e., GLPS (G), LVDD (L), VOThe Kaplan–Meier curves for the estimated composite adverse outcomes are presented based on hs-CRP, LVDD, GLPS, and oxygen pulse in Fig. N = 57, 50.4%) and scores of 2, 3, and 4 as the high-risk group  , we evaluated the diagnostic performance of the GLPS, LVDD, VOThe area under the curve, sensitivity, and specificity of GLVC and its constituent parameters are shown in Table p < 0.001, Fig. The Kaplan–Meier analyses and log-rank tests were performed to determine the prognostic value of GLVC in predicting adverse outcomes in patients with HF. The data demonstrated that adverse outcomes in the high-risk group were significantly higher than those of the low-risk group  in HF patients.Over the years, many predictors for HF exacerbation and mortality have been identified, including clinical, laboratory, and echocardiographic parameters. Several HF risk scores are currently used in clinical practice, for example, the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score  in HFrEFThe role of GLPS as a marker of cardiovascular events in HF population has been studied in some important publications over the years. In the Cho et al. study, GLPS was a predictor of the composite endpoint  in acute HF patients . Nahum eAlthough the role of EF in heart failure has been studied over the years, the LV diastolic diameter obtained routinely along with LVEF has not been considered for potential use in risk stratification yet. Left ventricle diastolic size could be a more stable measure in clinical practice. A potential limitation of EF is significant subjectivity. Publications have suggested that such variability in EF could be in the range of 10% or greater . Moreove2/HR) is a measurement of peak VO2 corrected for heart rate. It is a noninvasive indicator of stroke volume and arterio-venous oxygen difference. This parameter could be more dependent on cardiac pump function reserve because traditional measures of peak VO2 ignore heart rate response during exercise. This correlation was observed and explored earlier in some other studies. Cohen-Solal et al. study [p = 0.1). In another study [p = 0.05), with a strong trend toward lower values in those who died (mean 9.8 ml/beat). Also, Lavie et al. [Oxygen pulse ; for CV mortality HR 2.26 , and for non-CV mortality HR 2.96 ) [Hs-CRP cut-off value of 2.38 ng/l separated those HF patients with clinical events from event-free subjects evaluated in the present study conforms to values  presented by other authors. Moliner et al. revealed that more than half of hospitalized HF patients had a hs-CRP ≥ 2 ng/l , about 7 0.001)) . Also, a 0.001)) .By including all four biomarkers in the GLVC scoring system, we covered impaired LV diastolic and systolic function, impaired metabolic efficiency of the heart muscle, and other aspects such as inflammation in HF population.The big advantage of our model is being a comprehensive evaluation system that represents a patient’s condition from multidimensional HF aspects. However, all data in this study were collected from one relatively small sample of patients hospitalized due to HF. Therefore, large, multicenter studies are needed in the future.The current study has some limitations. The first and critical limitation is that there are no different datasets for a derivation and a validation. This is a preliminary study based on the small study sample from a single center. Second, the patient population was limited to those hospitalized due to HF in our Department, which could evoke referral bias because patients referred for hospitalization are not representative of the general HF population. The latest European Society of Cardiology guideline for HF  categori2/HR), in HF patients, is an easily available and effective tool and could be taken into account in the assessment prognosis of HF patients in the future. A personalized diagnostic process using the ECHO, CPET, and inflammatory biomarkers to assess the hemodynamic and clinical condition of individual patients may help identify those with a poorer prognosis.The novel personalized scoring system, based on biomarker of inflammation, i.e., high-sensitivity–reactive protein (hs-CRP), impaired left ventricular (LV) relaxation assessed as higher left ventricular diastolic diameter (LVDD), early predictor of LV systolic dysfunction, i.e., global longitudinal peak strain (GLPS) and a measure of the metabolic efficiency of the heart muscle, i.e., oxygen pulse (VO


Dietary data were evaluated through a validated form of a food frequency questionnaire. Exploratory factor analysis was used to extract major dietary patterns,. To assess the QoL, Euro-QoL five- dimension questionnaire was used. Latent class analysis was used to classify participants based on QoL. Multivariable logistic regression was employed to evaluate the association between dietary patterns and QoL.Three dietary patterns, i.e. western, healthy and traditional, and two classes, i.e. high and low quality of life. were identified from study participants. Lower adherence to the healthy dietary pattern increased the risk of being in low QoL class in which subjects in the lowest tertile of healthy dietary intake had higher odds of being in low QoL class (adjusted OR (AOR): 1.51, 95% CI: 1.19–1.91). However, subjects in the lowest tertile of traditional diet, low adherence, had 30% lower risk of belonging to the low QoL class . Higher adherence to western dietary pattern increased the risk of low quality of life, but it was not statistically significant.Higher adherence to a healthy diet and lower adherence to traditional dietary pattern were associated with better QoL in manufacturing employees.The online version contains supplementary material available at 10.1186/s12889-023-16898-9. According to the World Health Organization (WHO), quality of life (QoL) is defined as “An individual’s perception of their position in life in the context of the culture and value systems in which their lives in relation to their goals, expectations, standards and concerns” . QoL canQuality of work or productivity, which is reflected in absenteeism, presenteeism, productivity, and work performance, can be affected by the QoL , 5. The Recently, an interest in the impact of diet on QoL in health and diseases has increased. For instance, the association of single nutrients, food groups, and dietary interventions with QoL for several diseases, such as cancers, diabetes, irritable bowel syndrome, cardiovascular diseases, and obesity, has been explored –17. HoweAlthough investigating the effects of single nutrients and foods on health and diseases has enhanced our knowledge of the fundamental biological pathways involved in how diet influences body, considering the impact of diet, as a whole (dietary patterns), can provide more information regarding the appropriate dietary guidelines to decrease health problems, improve QoL of industrial workers, and reduce economic burden on their families, especially in developing nations .Dietary patterns can be defined by two approaches: a priori and a posteriori. In the priori approach, the scores of compliance to predefined diets are calculated , while in the a posteriori method, patterns can be driven using principal component analysis (PCA) or cluster analysis .To the best of our knowledge, only a few studies have been conducted to investigate an association between dietary patterns and QoL among industrial workers.. Considering that dietary patterns can provide important information about lifestyle of individuals as well as QoL and its effects on productivity and other aspects of QoL; therefore, we aimed to identify major dietary patterns and to evaluate their association with QoL among industrial employees.n = 437 employees) were excluded from the study. Considering that the number of female employees in each department was low, only 260 women, who were willing to participate in the study, all were included using the convenience sampling. Finally 3063 people with complete data have been subjected to data analysis. Prior to thier participation in the study, all subjects provided the written informed consent. More details about study structure and content have been presented previously [This cross-sectional study was conducted in 2015 on 3500 formal and contractual employees working in Isfahan Steel Company, Isfahan, Iran. The required sample size was determined to be 3500, considering the prevalence of the mental health problems as 0.1, type one error rate as 0.05, and a sampling error rate of 0.01 , 23. Oureviously . We follUsual dietary intake of the participants was assessed via a validated self-administered food frequency questionnaire (FFQ-short form) . If partIn this study, one of the most widely used generic instruments for assessing QoL, i.e., Euro QoL-five- dimension questionnaire EQ-5D-3L), was utilized . This isD-3L, wasNecessary information about the socio-demographic variables , job-related variables , and lifestyle variables  were collected by the validated structured and self-administered questionnaires. Physical activity was evaluated using the short form of the International Physical Activity Questionnaire (IPAQ), which is a valid tool to assess physical activity in the Iranian population . In thisTo extract the major dietary pattern, Exploratory Factor Analysis (EFA), based on Principal Component Analysis (PCA) extraction method, was performed on 38 food items and food groups. The orthogonal Varimax rotation procedure was used to find the interpretable factors. The number of factors to retain was guided by scree plot inspection and eigenvalues > 1. Post-rotated factor loadings showed that three interpretable dietary patterns were labeled based on food groups with the highest loading in each factor. For each dietary pattern, factor score was calculated by summing the intake of food items weighted by their factor loadings, and also a score for each identified pattern was allocated to each person. The participants were categorized based on tertiles of dietary pattern scores. This enabled us to evaluate the association of different levels of intakes from each dietary pattern with QoL in our study participants.Latent class analysis (LCA) was used to determine latent classes of employees based on their response to 5 domains of the EQ-5D. The modeling process was fitted as follows: in the first step, to classify the subjects according to their response to five items of QoL, LCA was used and LCA with different classes was fitted to define the optimal number of latent classes, and also the number of classes was increased from 1 to 5, successively. To attain the best fitting model, Bayesian information criterion (BIC) and the Lo–Mendell–Rubin likelihood ratio test were used , 29. DurBinary logistic regression was used to evaluate the association of dietary patterns as the independent variables in the crude model, and adjusted by age and sex (model 1), and age, sex, shifting work, smoking status, BMI, and sleep duration (model 2), with the extracted classes of QoL as the response variable. The last tertile of dietary pattern scores was considered as the reference category in the analysis. We also evaluated the association of each dietary pattern with the score of QoL assessed by VAS by using Pearson correlation and linear regression. Additionally, we compared mean score of each dietary pattern between people suffering and not suffering from each five problems evaluated by EQ-5D questionnaire by independent samples t-test and analysis of covariance after the adjustment for potential confounders.P < 0.05 was considered atasitically significant.Continuous and categorical variables were expressed as mean ± SD and number (percentage), respectively. Independent samples t-test for normally distributed variables and Mann–Whitney U test for non-normal quantitative variables, respectively, were used and also chi-square test was used to compare continuous and categorical variables in the study groups. One-way analysis of variance (ANOVA) and the chi-square test were applied to compare means of continuous and categorical variables across tertiles of dietary pattern scores, respectively. All statistical analyses were performed using SPSS version 16, and also A total of 3,063 participants who completed the questionnaires were included in the current study Fig. .Fig. 1FlTable P < 0.05).Table Table p < 0.05) and higher mean BMI (26.28 ± 3.78 vs. 24.76 ± 3.64) as compared with those in lower tertiles (p < 0.001). The participants in the upper tertile of healthy dietary pattern were predominantly male (31.1% vs. 30%), older (37.18 ± 7.17 vs. 36.32 ± 7.47), with rotational shift works (19.8% vs.16.2%), and without a second job, and also had a higher educational attainment (6–12 years) (21.8% vs.19.5%) (p < 0.05). Also, according to our results, subjects in the upper tertile of the traditional dietary pattern were significantly smoker (10.6% vs.9.6%), and rotational shift worker (19.4% vs. 16.9%), and also higher mean BMI (34.91 ± 3.68 vs. 26.14 ± 3.69), higher sleep duration (7.20 ± 1.17 vs. 7.02 ± 1.16)and different distribution of income level (p < 0.05).Table Table Also, we observed a significant association between traditional dietary patterns and QoL in which lower adherence to this type of dietary pattern decreased the odds of having low QoL. Subjects in the lowest tertile of traditional dietary pattern had lower risk of belonging to the low QoL class in both crude and adjusted models .Our results showed that the higher intake of western dietary pattern increased risk of low QoL, butthe association was not statistically significant.r = -0.093, P < 0.001) or positive  correlation between healthy and traditional dietary patterns and QoL, respectively. No significant correlation was observed between western dietary pattern and QoL . Linear regression analysis in unadjusted model showed a nonsignificant association between western dietary pattern and VAS score of QoL (regression coefficient (standard error (SE)) B = 0.0240(0.019), P = 0.21); However, after the adjustment for protentional confounder a significant positive association was detected (adjusted regression coefficient B(SE) = 0.049(0.02), P = 0.015).A significant negative regression coefficient was observed between healthy dietary pattern and VAS score of QoL (B(SE) = -0.104 (0.02); P < 0.001). After the adjustment for confounders, it was remained significant (B(SE) = -0.102(0.02), P < 0.001). The evaluation of the association between traditional dietary pattern and VAS score of QoL by linear regression in unadjusted model showed a significant positive relationship (B(SE) = 0.064 (0.021), P = 0.002) in adjusted model (B(SE) = 0.096(0.021), P < 0.001).We also evaluated the correlation between score of each dietary pattern and VAS score of QoL. Our results showed a significant negative (P < 0.001). People with mobility problem had significant lower mean score of healthy dietary pattern , those with pain/discomfort problem had significant higher mean score of traditional dietary pattern and lower mean score of healthy dietary pattern  and people with depression/anxiety problem had significant higher and lower, respectively, mean scores of traditional and healthy dietary patterns  as compared with those without the aforementioned problems .The mean score of each dietary pattern was compared between two extracted classes of QoL as well as between two categories (no problem and some or severe problems) of 5 dimensions of EQ-5D. The results are presented in Supplementary Fig. 1 and Supplementary Fig. 2 (panels A-E). The mean score of healthy and traditional dietary patterns is significantly lower and higher, respectively, in people in low QoL class compared with people in high QoL class  concentrations and deteriorate mental health, which can affect QoL . These fAlthough the association of western dietary pattern with QoL was not statistically significant in our study, previous studies showed that the western dietary pattern might be associated with lower QoL in all domains , 42. SevIndustrial employees are especially prone to low QoL, due to the long hours of work, fatigue, irregular sleep hours, and low income level in many of them. Healthy dietary patterns and healthy food choices corresponding to their situation and income level can be a helpful approach to improve their QoL by reducing the risk of chronic diseases and improving their mental status (37). Among variables confounding the association betwen dietary pattern and QoL, BMI and education level of people could be particularly important. Increased BMI could affect mobility, leading to osteoarthritis. Furthermore, higher BMI is associated with increased risk of chronic diseases, which can have a detrimental impact on QoL. , 45. TheHowever, this study has some limitations that should be addressed. First, we could not derive any cause-effect relationship from the findings of this study due to the cross-sectional design. Second, some subjective decisions were taken in factor analysis and latent class analysis regarding the extraction of dietary patterns and class of QoL, respectively, such as the number of factors and classes to be extracted and labeling of factors/ classes and interpreting the results. Third, self-report questionnaires were used to gather data in this study, which could lead to misclassification of participants and recall bias. Finally, the effect of ‘healthy worker’ could have occurred in this study. Despite the aforementioned limitations, this study has some strengths that should be highlighted. To our knowledge, this is the first study with alarge sample size that evaluated the association between dietary patterns and QoL among industrial employees using a comprehensive and advanced statistical method. Moreover, the impact of a wide variety of potential confounders on results has been adjusted in this study.The results of this study showed that adhering to a healthy diet was associated with better QoLin manufacturing employees. Also, lower adherence to the traditional dietary pattern of Iranian society was related to higher QoL. Health policy makers could use these findings to develop policies in order to improve dietary quality of employees, such as through education programs and considering accommodations for healthy dietary products. Furthermore, intervention studies are needed to investigate the effects sof different healthy dietary patterns, such as DASH and Mediterranean diet, on quality of life in manufacturing employees.Additional file 1. Mean score (95%CI for mean) of each dietary pattern in two classes of QoL.Additional file 2. Mean score (95%CI for mean) of each dietary pattern in two categories of mobility problem (A), self-care problem (B), daily activity problem (C), pain/discomfort problem (D) and depression/anxiety problem (E) as items of QoL.


The European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLQ-C30) is a validated and widely-used Patient-Reported Outcome Measure for measuring the health-related quality of life (HRQoL) of cancer patients. To facilitate interpretation of results obtained in studies using the EORTC QLQ-C30, we generated normative data for the Dutch general population, stratified by age and sex.Dutch participants were selected from a larger cross-sectional online panel research study collecting EORTC QLQ-C30 general population normative data across 15 countries. EORTC QLQ-C30 raw scores based on a 4-point response scale were transformed to linear scores ranging from 0 to 100. Transformed scores were weighted based on the United Nations population distribution statistics and presented by age and sex/age. Differences in scale scores of ≥ 10 points in HRQoL were applied to indicate clinical relevance.One thousand respondents completed the online survey. Stratified by age, clinically meaningful differences were observed, with worse physical functioning scores and better emotional functioning scores with increased age. Symptom scores remained stable across age groups, except for small age differences observed for fatigue, nausea/vomiting, diarrhoea, and financial difficulties. Stratified by sex/age, men generally scored better for both functioning and symptoms. However, these differences were not clinically meaningful.These updated normative EORTC QLQ-C30 for the Dutch general population can be used to better interpret HRQoL data obtained from Dutch cancer patients. Being part of a larger international study, these data can further be used for inter-country comparisons in multi-national studies. Patient-Reported Outcome Measures (PROMs) are questionnaires completed by patients to measure their quality of life. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire, the QLQ-C30, is a questionnaire widely used for cancer patients. To help interpret the scores that result from this questionnaire, scores can be compared with the scores from the general population, so-called normative scores. This study generated updated EORTC QLQ-C30 data for the Dutch general population that had been collected as part of a large European Norm Data project. This is important, because national normative data allows for more meaningful interpretation of scores within a specific country. Scores are presented separately for men and women, and for different age groups. We found that with increasing age, worse physical but better emotional functioning was reported. Men generally reported better functioning and fewer symptoms compared to women. The normative EORTC QLQ-C30 data for the Dutch general population can be used to better interpret data obtained from Dutch cancer patients. Patient-Reported Outcome Measures (PROMs), designed to quantify patients’ experiences with disease and treatment, have been increasingly applied in oncology trials and observational studies over the past decades . The EurAn important strategy to aid in the interpretation of cancer patients’ HRQoL is to compare these with general population scores, so-called normative data . In 2017Van de Poll-Franse et al.  publishen = 100/stratum). Participants were voluntary online panel members who gave consent to participate in panel-based studies. Data were collected by the panel research company GfK SE (https://www.gfk.com/). For a given country, panels are representative for the general population with internet access based on criteria including age, sex, education, household size, city size, and geographical location. Response rates to panel studies conducted by GfK are generally between 75 and 90% [Dutch general population data were retrieved from an international online cross-sectional study undertaken in March/April 2017, in which participants completed a survey about HRQoL; for further details on the data collection methods, please see Nolte et al.  and Lieg and 90% .The EORTC QLQ-C30 : 30 itemSociodemographic items, including sex, age, educational level, employment status, relationship status, and prevalence of health conditions.Participants were asked to complete a questionnaire that, among other data  containd) to better understand the size of detected differences. First, sociodemographic data and EORTC QLQ-C30 mean scale scores and standard deviations (SD) were described. The EORTC QLQ-C30 summary score, available since 2016, was the mean of all EORTC QLQ-C30 scale scores ; the Summary score ranges from 0 to 100, with higher scores indicating better HRQoL [The purpose of collecting norm data from the general population is to guide interpretation of HRQoL data obtained from cancer patients . Therefoer HRQoL . It has er HRQoL .Second, to achieve norm scores to be representative for the Dutch general population, mean scale scores were weighted by the sex and age distribution of the adult Dutch population , using tN = 1000). Their mean age was 54.0 years (SD: 15.3 years), 42% completed university or a post-graduate degree, and 73% were married or in a stable relationship. Thirty percent were employed full-time, 19% part-time and 31% were retired. Half of them reported having at least one health condition. The most frequently reported health conditions were chronic pain (15%), arthritis (10%), diabetes (8%), and heart disease (6%); 2.3% reported a diagnosis of cancer.Unweighted and weighted sample population characteristics are presented in Table Weighting the population altered the age distribution slightly with more respondents in younger age categories, because the 18–39 years age group had a larger range compared to the 10-year range for the other age groups.Weighted and unweighted EORTC QLQ-C30 scores are presented in Table Weighted mean and SD for global health were 77.4 ± 19.8. Functioning scores ranged between 82.3 ± 21.2 for emotional functioning and 91.9 ± 19.0 for social functioning. Symptom scores ranged between 3.5 ± 11.8 for nausea/vomiting and 23.7 ± 23.0 for fatigue. For several symptom subscales , floor effects were observed, as > 80% selected the best score. The weighted mean EORTC QLQ-C30 summary score was 88.6 ± 12.1.d: = 0.65), although not clinically meaningful, while emotional functioning was better  with increasing age . Differences in other functioning scale scores were not clinically meaningful and relatively stable across age groups (Table d = 0.56).Weighted EORTC QLQ-C30 scores stratified by age are presented in Table d = 0.49), while the mean EORTC QLQ-C30 summary score was relatively stable across age categories .Mean Global HRQoL was better with increasing age , role , social , and emotional  functioning, and global health  were 3–4 points higher in men. Men reported more favourable symptom scores than women for insomnia , pain , fatigue , and dyspnoea . The mean EORTC QLQ-C30 summary score was again slightly more favourable for men . None of these were clinically meaningful.Scores stratified by age and sex are presented in Table The age patterns described above were found for both men and women. For physical functioning, scores were worse with increasing age , for emotional functioning, scores were better with increasing age . Varying patterns were found for the association between age and symptom experience.This study describes Dutch EORTC QLQ-C30 normative data stratified by age and sex. Mean functioning ranged between 82 and 92 points (with 100 points indicating perfect functioning), while symptom scores ranged between 4 and 24 points (with 0 indicating no symptom burden). Clinically meaningful trends were found for emotional functioning (where scores were better with increasing age), similar to other recent publications in this area –18. MostDutch general population data for the EORTC QLQ-C30 have been published previously by van de Poll-Franse et al. based on a 2009 survey of 1700 individuals . SimilarContrasting to van de Poll-Franse et al.  and MolsComparing our data to Statistics Netherlands 2017 suggests that the study data are representative in terms of most basic individual characteristics  . Since 92 ≤ 0.015).The mean functioning scores we report (between 82 and 92) are, together with scores from Austria (between 78 and 92 ), among In the current study, we observed floor effects for several symptoms, suggesting that a large proportion of the general population are not affected by these symptoms; hence, specific items of a cancer-specific questionnaire may not be applicable to them. However, the main aim of the current study was to provide a reference for users of the QLQ-C30 to enable them to put their cancer patients’ scores into context. Therefore, knowing that the prevalence of certain symptoms is very low in the general population is an important finding, too. Further, we are presenting mean scores in keeping with the other norm data publications –18; howeIn clinical practice, both reference data from other cancer patients and general population normative data can aid in the interpretation of HRQoL data obtained from cancer patients. The importance of stratified comparison is underlined by the differences in functioning and symptoms we found between men and women, and between different age categories. Comparison with normative data is particularly interesting for determining the effect of cancer and cancer treatment on long-term survivorship: 60% of Dutch cancer patients will live at least five years after a cancer diagnosis . The upd