To analyze the relationship between tumor volume in Endometrial Cancer (EC) on Magnetic Resonance Imaging (MRI) and lymph node metastasis to establish which patients benefit from omitting the lymphadenectomy.A retrospective observational study with 194 patients with EC identified between 2016 and 2021 at the Juan Ramón Jiménez University Hospital, Huelva (Spain) was carried out. Preoperative MRI of 127 patients was assessed. The tumor volume was analyzed on MRI by the ellipsoid formula and another alternative method with a manual ROI in different sections. Risk factors for node metastases were analyzed to understand its relationship and to identify an optimum criterion for the tailored surgery.p = 0.001), tumor with a volume greater than >25 cm3 (p < 0.001), lymphovascular space invaded (p = 0.007), and preoperative Ca 125 serum >28 (p < 0.001). Multivariate analysis indicated that tumor volume index >25 cm3 was an independent risk factor for lymph node metastases. The patients without significant proposed risk factors  did not present lymph node metastases, independent of myometrial invasion.Univariate analysis showed risk factors for lymph node metastases were histological grade , and tumor volume on MRI greater than 25 cm The therapeutic effects of pelvic and para‐aortic lymph node removal is a matter of great debate.The pelvic magnetic resonance imaging (MRI) is the method of choice for preoperative staging.It is already known that tumor size is an important prognostic factor in EC, existing a strong correlation between tumor size higher than 2 cm and the risk of nodal disease and worse overall survival, even in patients in an early stage and low‐grade EC.The main objective of this research was to explore the relationship between the tumor volume in the EC in the MRI and the lymph node metastasis.22.1An observational retrospective study of a prospective database was conducted. 194 women diagnosed with EC between January 2016 and December 2021 at the Juan Ramón Jiménez Hospital in Huelva (Spain) were included.127 patients were studied preoperatively using magnetic resonance imaging. All patients were treated according to current guidelines. For the analytical study, only these 127 patients were included, diagnosed with low‐intermediate‐high‐risk endometrioid carcinoma with preoperative MRI and staging surgery performed. The study was approved by the Huelva Regional Research Ethics Committee (2534‐N‐21). Patients who were not assessed through preoperative MRI were excluded from the study.Patients' medical histories were studied in order to detect risk factors for lymph node metastasis. The variables used were: (1) histological type, (2) tumor grade, (3) myometrial invasion, (4) Ca125 level, (5) MRI volume index, and (6) lymphovascular space invasion (LVSI).Every variable was stratified using a binary classification. (1) Histological type was classified into endometroid/nonendometroid, (2) tumor grade into G1/G2 versus G3. (3) Myoinvasion was classified according to the revised FIGO system 50% versus ≥50%. (4–5) Volume index and Ca125 level serum were classified into two categories using the measurement obtained by the Receiver Operating Characteristics (ROC) curve for lymph node metastasis based on sensitivity and specificity. LVSI determination was reported preoperatively and confirmed on the final histology in all included patients.2.22 and corresponding apparent diffusion coefficient (ADC) maps. Additional sequences (weighted on T1 or T2 with fat saturation) as well as the use of T1 sequences with fat saturation after administration of gadolinium were used at the discretion of the supervising radiologist of the study. MRIs were analyzed by a radiologist with more than 10 years of experience in gynecological cancer imaging.Preoperative pelvic MRI was performed using equipment with a 1.5 T magnetic field . High‐resolution T2‐weighted turbo spin‐echo sequences were performed (3 mm slice thickness) in the three orthogonal or oblique planes appropriate for the major and minor axes of the body of the uterus, as well as diffusion‐weighted planar echo sequence (DWI) with a maximum b value >600 s/mmπ/3]). The neoplasm/uterus volume ratio (N/U) was calculated. Subsequently, a manual calculation of the volume was carried out by contouring the lesions or region of interest (ROI) in which the neoplasm showed the largest size in T2W, using the standard software .The estimated volumes of the neoplasm and uterus have been calculated using an ellipsoid formula , κ = 0.21–0.40 (fair), κ = 0.41–0.60 (moderate), κ = 0.61–0.80 , and κ ≥ 0.81 . To study the predictive factors that determine lymph node metastases as independent risk factors, a logistic regression analysis was performed. Initially, a univariate analysis was performed and those factors with a significance below p = 0.1 were the variables included in the multivariate logistic regression analysis as independent, thus establishing the regression model. Odds Ratio (OR) and Confidence Intervals (CI) were calculated and reported. In all cases, a statistical significance of 5% (p < 0.05) was required. Statistical analyses were performed using the SPSS statistical program, version 24.0.Continuous variables are reported as mean ± standard deviation (SD) or median with interquartile range (IQR), and all categorical variables are reported as number and percentage. Normality was evaluated using the Kolmogorov–Smirnov test. Comparisons between categorical variables were analyzed using the Chi‐squared test. For continuous variables, comparisons were made using the Mann–Whitney 3A total of 194 patients with endometrial cancer were identified over the period of study with a mean follow‐up period of 66 months.Surgical and baseline characteristics were as follows: the median age was of 63.73 years (range 28–91) and 82.56% were postmenopausal. The predominant histological subtype was endometrioid with a rate of 84.5%. Of the 194 patients in the cohort, 179 underwent complete surgical staging and ninety‐seven patients (54.18%) had pelvic lymph node sampling, while 43 (24.02%) had accompanying para‐aortic lymph node sampling. The mean number of nodes dissected was 13 (range 4–24) in the pelvic lymphadenectomy and 20 (range 5–30) in the para‐aortic lymphadenectomy. Regarding the stage of the patients, 80 were IA FIGO stage (41%), while 50 were FIGO stage IB (25.3%); 1 (0.5%) had cervical stromal invasion (FIGO stage II); 43 were stage III (22.1%); and 7 were stage IV (3.6%). 20 patients (12.2%) presented lymph node metastases. Adjuvant treatment was given to 117 (60.30%) patients; 46 (23.71%) were submitted to chemotherapy; external radiation therapy was applied in 10 patients (5.1%); brachytherapy was administered in 98 (50.51%) of the patients; and 6 (3%) patients were treated with hormonal treatment (Table 3 tumor volume was identified as a predictor of lymph node metastases with a sensitivity and specificity of S72% and E84% and area under the curve (AUC) of 0.82. A cut‐off value of 28 of CA 125 classified node lymph metastasis into two groups of high and low risk, through ROC curves with an AUC of 0.81 and sensitivity and specificity of S78% and E80% , volume index >25 (p < 0.001), LVSI (p = 0.002), and Ca 125 (>28) (p < 0.001). There was no significant difference in MRI between patients of age > 60 (p = 0.85) and myometrial invasion ≥50% (p = 0.20). Multivariate analysis confirmed that volume index >25 , Ca 125 > 28 , and high histological grade  were independent prognostic factors to lymph node metastasis. LVSI (p = 0.4) was not a significant independent risk factor for lymph node metastases, therefore, it was not included in the multivariate study   and the presence of lymph node metastasis. The algorithm stratified patients according to the presence of risk factors. Patients with no significant risk factors did not present lymph node metastases. In cases with one risk factor (Ca125 > 28), the rate was 1.3%, which rose to 20%, 40%, and 80% in cases with two, three, and more than three risk factors, respectively.N = 65), 22 patients presented deep myometrial invasion, all of them with no node metastases associated. In the group with only one risk factor (Ca 125), the presence of myometrial invasion was found in only 22 patients, and the presence of lymph node metastases disappeared. In cases with two risk factors, the adjusted rate of lymph node metastases was 20%, which rose to 30% and 50% in the group with three or more than three, respectively , and extensive LVSI involvement, are poor prognostic criteria that suggest the use of postsurgical adjuvant therapy.Lymph node involvement is an independent prognostic factor,In fact, several studies have previously proposed the criterion for assessing the risk of EC. MarianiThe discrepancy between the pre‐ and postsurgery findings generated the search for new preoperative tools that allowed a correct tailored surgery. Preoperative tumor volume cannot be routinely correlated with definitive histology, but it is a radiological parameter independent of myometrial infiltration. The introduction of ROI as a method of volume measurement is especially useful with tumors given their irregular contour, which does not allow for other traditional calculations such as the ellipse formula. Some authors have recently introduced tumor size in the algorithm through PET imaging,Limitations of the study include omitting molecular parameters, recently introduced in the algorithm for the management of EC, as well as omitting the sentinel lymph node since it was not studied in the entire study population and is a source of bias. Also, the inability to correlate the preoperative radiologic tumor volume with the volume of the surgical specimen is considered a limitation.3) associated with a null rate of lymph node metastases. Myometrial invasion on MRI was not a significant risk factor for node metastasis in the performed analysis, so it was omitted as a risk factor in the strategy. Based on the findings, high‐grade tumor, Ca 125 elevated (>28), and Tumor volume on MRI greater than 25 cm3 were considered high‐risk factors for node metastasis.Based on all the above described, the volume index as a new MRI risk factor was introduced in the present study, finding an optimal cut‐off point , Ca 125 > 28 , and high histological grade  were independent prognostic factors for lymph node metastasis.To sum up, the proposed algorithm score may provide useful information for stratification of the risk of node metastasis, and the present findings suggest that lymphadenectomy can be omitted in cases with no risk factors, according to this node metastasis score.Elga López‐González: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; resources ; software ; supervision ; validation ; visualization ; writing – original draft ; writing – review and editing . Alberto Rodríguez‐Jiménez: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; resources ; software ; validation ; visualization ; writing – original draft ; writing – review and editing . José Antonio Rojas‐Luna: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; resources ; supervision ; validation ; visualization ; writing – original draft ; writing – review and editing . Cinta Daza‐Manzano: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; resources ; software ; validation ; visualization ; writing – original draft ; writing – review and editing . Juan Gómez‐Salgado: Conceptualization ; data curation ; formal analysis ; investigation ; methodology ; project administration ; resources ; software ; supervision ; validation ; visualization ; writing – original draft ; writing – review and editing .There were no sources of funding.The authors declare that they have no competing interests.


The aetiology of cryptoglandular anal fistula (AF) is poorly understood. Evidence suggests that persistence and/or recurrence of the disease is more related to inflammatory than infectious factors. The aim of this study was to investigate the immune profile of cryptoglandular AF and to perform a histopathological characterization.Fistulectomy was performed in all patients; healthy ischioanal fat from the same patients was used as a control. Samples were evaluated by the Luminex xMAP system for the detection of 27 analytes. AF tissues were analysed using immunofluorescence. Staining was performed using primary antibodies to identify M1 inflammatory and M2 anti‐inflammatory macrophages. Selective staining of total T lymphocytes and different T lymphocyte subsets was performed.Twenty patients with AF underwent a fistulectomy. Specific cytokine pathways differentiated AF from healthy tissue: pro‐inflammatory cytokines interleukin (IL)‐1β, IL‐4, IL‐8 and IL‐17 and the anti‐inflammatory cytokine IL‐10 were overexpressed in AF compared with controls. Chemokines involved in macrophage recruitment  were higher in AF than in healthy fatty tissue. Moreover, we showed that Tc17 cells characterize AF patients, thus confirming the enzyme‐linked immunosorbent assay data. Furthermore, elevated infiltration of CD68+ myeloid cells and a reduction of the M1/M2 ratio characterize AF patients.A combination of inflammatory cytokines, chemokines and growth factors reside in the wound microenvironment of AF patients. For the first time an important prevalence of Tc17 cells and a reduction in the M1/M2 ratio was observed, thus suggesting new insights into the immunological characterization of AF patients. The aetiology of cryptoglandular anal fistula is still poorly understood. This study provides a complete analysis of the immunological microenvironment related to the disease; moreover, for the first time, a specific cell population potentially related to this condition has been described.Surgical treatment of anal fistula (AF) is still a debated issue in proctology . Each thAcute, self‐limiting and resolving inflammation is critically important in the repair process of injured tissues. In contrast, chronic inflammation can lead to excessive tissue damage and deregulated tissue healing. Evidence suggests that epithelialization of the perianal fistula tract and persistence of chronic inflammation may play a decisive role in disease persistence and recurrence , 6, whilThis was a prospective observational study conducted at the Proctology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy between May 2020 and April 2021. The local ethics committee approved the study (Prot. ID 2354). All patients signed a written informed consent.A consecutive series of patients referred to our unit and affected by cryptoglandular AF were evaluated by clinical and physical examination . Moreover, all patients were preoperatively assessed by three‐dimensional endoanal ultrasound . A screening endoscopic colorectal evaluation was prescribed according to common guidelines . InclusiThis study did not alter the scheduled treatment for the patients, so they were therefore treated according to the usual procedures of our unit.Two enemas were given before the procedure as bowel preparation, and no antibiotic prophylaxis was prescribed. All patients were treated in the lithotomy position, under general or locoregional anaesthesia; all operations were performed by the senior colorectal surgeon (CR).The fistula tract and its internal anal opening were explored using a probe and by hydrogen peroxide injection. A complete fistulectomy was performed from the external to the internal fistula opening; then an endorectal flap, closure of the internal opening, sphincter reconstruction or placement of a seton were performed. A macroscopically healthy sample of perianal fat located near the excised fistula was taken from each patient and used as a control.Immediately after the surgery the collected specimens were quickly frozen in liquid nitrogen and stored at −80°C for subsequent molecular analysis. Part of the excised tissue was also placed in formalin, paraffin embedded and collected for immunohistochemical analysis.g for 4 min; supernatants were then collected and stored at −80°C before cytokine analysis. The protein concentration was analysed by Bradford Assay (Bio‐Rad). The multiplex cytokine assay was performed using 500 μg/ml of lysate protein. Multiplex analysis (Bio‐Plex Multiplex Immunoassay System) was performed according to the manufacturer's instructions. IL‐1β, IL‐1RA, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐9, IL‐10, IL‐12, IL‐13, IL‐15, IL‐17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony‐stimulating factor (CSF), granulocyte monocyte (GM)‐CSF, interferon (IFN)‐γ, IFN‐γ‐induced protein 10, monocyte chemoattractant protein‐1, macrophage inflammatory protein (MIP)‐1α, platelet‐derived growth factor‐BB, MIP‐1β, regulated upon activation, normal T cell expressed and presumably secreted (RANTES), tumour necrosis factor (TNF)α and vascular endothelial growth factor were analysed. Results were analysed using dedicated Bio‐Plex Manager software and are expressed in picograms or nanograms per millilitre as appropriate.Tissue samples were thawed, and the washed tissue was cut into small pieces (3 mm × 3 mm) with a knife and homogenized with a mechanical shear homogenizer . The tissue was homogenized in ice and stroked 20 times, pausing for 10–15 s between each homogenization in cell lysis buffer  containing protease inhibitor cocktail  and 3 μl of a stock solution containing 500 mM phenylmethylsulfonyl fluoride (#P‐7626) in dimethyl sulphoxide . The ground tissue was transferred to a clean microcentrifuge tube and frozen at −80°C for 24 h. The next day the samples were thawed, sonicated on ice and centrifuged at 4500Immunofluorescence studies were performed on sections of mucosal tissue and control samples represented by marginal ischioanal tissues, a region with limited immune cell infiltration and representative of the normal immunological distribution .Paraffin‐embedded sections were dewaxed. Antigen retrieval was performed with HIER Buffer L  at 98°C for 20 min. Nonspecific antigen binding was blocked with 10% normal goat serum (Thermo Fisher Scientific).Immunofluorescence staining was performed to characterize immune cell infiltrates. T lymphocytes were stained with anti‐human CD3 , anti‐IL‐17A  and anti‐CD8a , both purchased from Abcam. For macrophage subset characterization, samples were stained with pan anti‐human CD68 , anti‐human iNOS/NOS II, NT  and anti‐human CD163  specific antibodies. All incubations with primary antibodies were performed overnight at 4°C.https://imagej.nih.gov/ij) and semi‐quantifications of positive signals from at least three random high‐power fields were analysed, counted and expressed as percentage of total CD3 (for T lymphocytes) or total CD68 (for macrophages). Importantly, T lymphocytes were distinguished by positivity for pan CD3 marker and positive co‐expression of IL‐17A (for CD4+ Th17) or CD8a (for CD8+ T lymphocytes). The resulting cells positive for both IL‐17A and CD8+ were classified as CD8+ Tc17 cells as previously reported [Secondary staining was performed with secondary antibodies and control isotype: anti‐mouse in horse 594 (DI‐2594), anti‐rabbit in goat 594 (DI‐1594), anti‐mouse in horse 488 (DI‐2488), anti‐rabbit in goat 488 (DI 1488), anti‐mouse in horse CY5 (CY‐2500) and anti‐rabbit in goat CY5 (CY‐1500) all from Vector Laboratories . All secondary antibodies were used at a final concentration of 10 μg/ml and were all purchased from Vector Labs. Images were acquired using a Nikon Eclipse Ni‐U microscope at 20× and 40× magnification. Images were processed with ImageJ software  and compared using the Mann–Whitney test. Categorical data are presented as frequencies and percentages and compared using the chi‐square test. Evaluation of the cytokine pattern was performed through measurements of the expressions of the considered cytokines .t‐test using Prism 8 (GraphPad Software). Values of p < 0.05 were considered significant. Analyses were performed using SPSS® version 21.0 for Windows® software (SPSS).The data representative of the histopathological characterization are shown as violin truncated plots with Tukey variations from at least 20 patients and five controls, from at least three independent experiments. Differences between experimental and control group were analysed by a two‐tailed unpaired Student's Twenty patients  fulfilled the inclusion criteria and were enrolled in the study. Nine out of 20 patients (45%) were affected by recurrent AF, with the internal fistula opening located anteriorly in eight cases , closure of the internal fistula opening in five cases (25%) and endorectal advancement flap and primary sphincter reconstruction in two patients (10%). The mean duration of the surgical procedure was 28.4 min (range 19–46 min), with a mean duration of hospital stay of 0.8 day (range 0–1 day). No complications or worsening of continence were registered, so the CCFIS did not change when assessed at the 6‐month follow‐up visit.p = 0.014, 0.004, 0.001 and 0.002, respectively) when compared with control tissue, while TNFα levels were no different  expression Figure .In order to investigate the phenotype of macrophages involved in the process of wound healing, and also in light of previously published data indicating an increased expression of IL‐1β in AF patients, we analysed the distribution of M1 and M2 macrophages in AF tissue samples compared with control samples Figure .We found a strong, statistically significant infiltration of CD68+ myeloid cells Figure . The disSurgical treatment of AF is still a debated topic as many aspects are not yet fully known . Most stIn this study, we report for the first time the prevalence of peculiar CD8 lymphocytes in AF tissues characterized by the expression of the inflammatory cytokine IL‐17, also known as Tc17 . We founNormally, Th17 as well as other T lymphocyte subsets are present in the intestinal mucosa to maintain immunity against pathogens and at the same time guarantee a state of tolerance towards commensal bacteria representing the microbiota . In AF pAs mentioned earlier, Th17 T lymphocytes play a pivotal role in the rectal mucosa. In fact, these cells play a protective role by promoting the maintenance of the integrity of the mucosal epithelial barrier , 25. Th1CD8 cells have been reported as cells capable of cytotoxic activity by producing IFN‐γ and performing clearance of virus‐infected cells . RecentlA general increase in the frequency of Tc17 has been described in many diseases where the inflammatory response is altered, such as systemic lupus erythematosus and psoriasis , 31, as Moreover, we observed an increased recruitment of cells positive for the expression of the pan macrophage marker CD68 in AF sections compared with control tissue. This is also reflected in an increased polarization of macrophages towards the M1 inflammatory subset, as highlighted by the increased amount of IL‐1β emerging from the Luminex analysis and confirming our previously published observations . We did The increased number of M1 macrophages was balanced by an increase in M2 macrophages, thus resulting in a reduction of the M1/M2 ratio. This was previously reported in other pathologies such as rheumatoid arthritis . The redIndeed, macrophage polarization is a finely regulated process related to resolution of the inflammatory state. In fact, this process occurs even in nonresolving inflammation, since macrophage polarization functions try to restore tissue homeostasis , 43.Limitations of this study are the relatively small sample size, which prevented any subgroup analysis on the clinical outcome, and the absence of an adequate control tissue, which has also been reported by others . As a maA complete analysis of the cytokine pattern characterizing AF patients has been reported. Moreover, our study has identified, for the first time, an important prevalence of CD8 T lymphocytes secreting IL‐17 (Tc17): this finding could shed new light on the identification of potential treatments that could restore the homeostasis of the tissue microenvironment by targeting the CD8 compartment or trying to re‐educate the altered immune system of these patients.Therefore, further studies will be necessary to explore the mechanisms that regulate the inflammatory response in AF patients, and to establish a causal relationship of the immunological mechanism responsible for the polarization of CD8 T lymphocytes to become Tc17.No funding was available for this study.The authors declare no conflict of interest.Study conception: FL, DL, APap, OP, AS, CR. Acquisition of data: SF, APar, CRT, PC, ARS, MCG; Data analysis and interpretation: FL, DL, APap, ARS, MCG, OP, AS, CR; Manuscript drafting: FL, DL, AP; Manuscript revision: SF, APar, CRT, PC, ARS, MCG. Critical revision/supervision: OP, AS; CR; Final approval: FL, DL, APap, SF, APar, CRT, PC, ARS, MCG, OP, AS, CR.The study was approved by the local Ethics Committee (Prot. ID 2354).Patients signed a written informed consent.


Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all‐cause mortality.We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid‐femoral (cfPWV) and femoral‐ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic‐femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log‐transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis.R = 0.078, −0.193, −0.155, −0.153, −0.116, and −0.137, respectively) and cfPWV . Compared with the lowest tertile of afSG, the risk of all‐cause mortality was lower in the highest tertile .Among 1079 diabetic patients, biomarkers including high‐density lipoprotein cholesterol, glycated hemoglobin, high‐sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG  among diabetic patients.This study investigates the relationships of serum laboratory tests with PWV and explored the associations between PWV and all‐cause mortality among diabetic patients.Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV among diabetic patients.Our research was the first to demonstrate that higher aortic‐femoral arterial stiffness gradient was associated with lower all‐cause mortality in diabetic patients, independent of a wide range of covariates. In particular, the carotid‐femoral pulse wave velocity (cfPWV) test is the recommended gold standard for measuring arterial stiffness in clinical practice.Traditional diabetic risk factors, including hypertension,22.1n = 1147), nondiabetic populations (n = 2554), those with coronary heart diseases (n = 902), and with missing biomarkers (n = 116) or covariates (n = 52), resulting in a final sample of 1079  Study is a population‐based, longitudinal study of 15 792 men and women aged 45–64 years enrolled between 1987 and 1989 from four US communities . Participants underwent follow‐up clinical examinations every 3 years denoted as Wave 2 (1990–1992), Wave 3 (1993–1995), and Wave 4 (1996–1998) visits. Fifteen years later, 5850 participants were invited back for the following three visits: Wave 5 (2011–2013), Wave 6 (2016–2017), and Wave 7 (2018–2019). Details of the ARIC study have been described previously.9 Figure . We furt2.22.2.1After participants stayed in the supine position for 5–10 min, technicians measured their cfPWV and femoral‐ankle PWV (faPWV) following a standardized protocol and using the automated cardiovascular screening device VP‐1000 Plus .2.2.2https://sites.cscc.unc.edu/aric/sites/default/files/public/manuals/Manual%208%20Laboratory%20Determinations%20revised%2009242012.pdf). Rigorous quality control and correction were performed for technical outliers by referencing the National Committee for Clinical Laboratory Standards .Each blood biochemistry test in the Wave 5 was categorized as either “lipid metabolism” , “blood glucose monitoring” , “complete blood counts” , “myocardial injury” , “inflammation” , “renal” , or “thyroid index” , triiodothyronine, thyroid stimulating hormone, and thyroid peroxidase antibody). The Atherosclerosis Laboratory  performed assays related to lipid metabolism, blood glucose monitoring, complete blood counts, myocardial injury, and inflammatory indicators. The Clinical Chemistry Laboratory  examined the renal and thyroid indexes. The details of specific equipment and materials used to measure each biomarker were obtained from ARIC  telephone calls and linkage to local hospital and state health department records. The follow‐up period was calculated from the date of participation in Wave 5 until death or the end of the follow‐up, whichever occurred first.2.42), physical activity (yes or no), self‐reported disease history , and use of medications including antihypertensive drugs, hypoglycemic drugs, lipid‐lowering drugs, anticoagulants, and statins. Medication information was obtained from diagnosis by a physician or the 2004 Med Code.The following covariates were demonstrated in previous studies to be associated with carotid atherosclerosis risks among diabetic patients2.5n) and percentages (%). One‐way analysis of variance (ANOVA) and χ2tests were used to test the significance of differences among more than two groups for continuous and categorical variables, respectively. The Kruskal–Wallis H test was used as a nonparametric alternative for ANOVA. Correlations of biomarker levels with afSG, cfPWV, and faPWV were calculated by Spearman rank correlations. To further evaluate potentially linear relationships, the biomarkers and PWV were then both log‐transformed and correlated using Pearson correlations.To assess the normality of continuous data, we utilized the Kolmogorov–Smirnov test. Normally distributed data were reported as mean (SD). If normality was not observed, then we reported the data as median (interquartile range). Categorical data were reported as frequencies (p > .05) were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all‐cause mortality according to tertiles of the cfPWV, faPWV, and afSG levels. Associations of PWV measurements with all‐cause mortality among diabetic patients were calculated for the unadjusted model, by adjusting for age and sex (Model 1), and adjusting for variables included in Model 1 plus race, smoking status, drinking status, BMI, physical activity, antihypertensive drugs, hypoglycemic drugs, lipid‐lowering drugs, anticoagulants, statins, stroke, myocardial infarction, heart failure, and cancer (Model 2). A sensitivity analyses was undertaken, and we analyzed the association between afSG and all‐cause mortality by excluding participants who developed CVDs or cancer in the follow‐up. We also performed subgroup analyses stratified by sex , age (<75 years or ≥75 years), race , drinking status (current drinker or not), smoking status (current smoker or not), history of CVD (yes/no), use of antihypertensive drugs (yes/no), and hypoglycemic drugs (yes/no). The product items of the aforementioned layered factors and afSG were incorporated into multivariate Cox regression models (based on Model 2) as interaction terms to test whether an interaction occurs and evaluate the robustness of our main results.To explore the association of PWV measurements with the risk of all‐cause mortality, multivariable‐adjusted Cox proportional hazards models  with PWV measurements were recruited in Wave 5. Table 3.2p < 0.05), whereas HDL‐C levels increased (p = 0.04). The correlations between biomarker levels and PWV measurements were assessed using Spearman rank correlation analysis (Table R = 0.175), albuminuria (R = 0.202), hs‐TnT (R = 0.128), and cfPWV, and between fasting glucose (R = 0.102), creatinine (R = −0.116), CysC (R = −0.193), platelet count (R = 0.164), HCT (R = 0.149), RDW (R = −0.163), CRP (R = −0.133), and faPWV. Slight correlations were found for HbA1c, creatinine, CysC, albuminuria, RDW, hs‐TnT, and afSG . Biomarker levels and PWV measurements  were both log‐transformed and subjected to Pearson correlation analysis, for which similar results were obtained.The median (interquartile range) levels of biomarkers according to afSG tertiles are described in Table is Table . Moderat3.3p = .018). Compared with the lowest tertile of afSG, the HR (95% CI) of mortality in the highest tertile was 0.543 (0.328–0.900) (p for trend = .012). These differences were also presented visibly based on the adjusted Kaplan–Meier survival curves deaths occurred. Table 0.543 0.38–0.900 . To confirm whether the correlation between afSG (categories) and all‐cause mortality is robust in different subgroups, subgroup analyses were also performed (Table p for interaction = .002). No significant interaction was found in the subgroups of age, race, current smoking, current drinking, history of CVDs, antihypertensive agents, and hypoglycemic drugs. The special results related to cfPWV and faPWV (categories) can be found in Table We conducted a sensitivity analysis to assess whether patients with CVDs or cancer had a confounding effect on the association of afSG and the risk of all‐cause mortality. As shown in Table ed Table . The ass4In this population‐based study, certain biomarkers including HDL‐C, HbA1c, hs‐TnT, CysC, albuminuria, and creatinine significantly correlated with PWV in diabetic patients. Further, afSG was associated with decreased risk of all‐cause mortality, suggesting it might be an independent predictor of mortality among diabetic individuals.To our knowledge, few studies have investigated the association of large‐scale biomarkers and PWV among diabetic patients. Previous studies have shown that an increased HDL‐C level is considered an important protective factor against cardiovascular disease.Moreover, we established that certain biomarkers related to renal function  were positively correlated with cfPWV and negatively correlated with afSG in diabetic patients. For renal biomarkers, our results were consistent with previous studies that demonstrated that CysC was associated with increased arterial stiffnessArterial stiffness has been related to all‐cause and cardiovascular mortality.The strengths of this research include a comparatively large sample among diabetic patients, a prospective study design, and the investigation of the involvement of other potential confounding factors. In addition, we conducted a comprehensive analysis of the relationship between a panel of biomarkers and PWV and further explored the connection between arterial stiffness with mortality, thereby providing additional reliable evidence for the prevention of carotid atherosclerosis in the diabetic population. Our study inevitably has certain limitations. First, this work is an observational cohort study of the association between biomarkers and PWV, as such, causality in the findings could not be determined. Second, only one‐time measurement was used for each parameter, the relationship between changes in biomarkers over time and PWV require further explorations. Third, we have not taken into account the potential effects of dietary habits. Finally, as this cohort enrolled mainly elder diabetic patients, our results might also not be generalized to younger individuals with diabetes.5Certain biomarkers related to lipid metabolism, blood glucose monitoring, myocardial injury, and renal function are significantly correlated with PWV in diabetic patients. Furthermore, afSG may be an independent predictor of mortality in the diabetic population. Early monitoring of these biomarkers could serve for atherosclerosis prevention, thus reducing the risk of cardiovascular events or death among diabetic individuals. Further prospective studies are warranted to investigate the association between these biomarkers and artery stiffness in the setting of diabetic events.Yong‐Qi Liang and Rui Zhou made substantial contributions to conception and design equally and thus are considered co‐first authors. Yong‐Qi Liang conducted statistical analyses, and wrote the manuscript. Rui Zhou provided substantial contributions to the design, analysis, and interpretation of data. Hao‐Wen Chen, Bi‐Fei Cao, Wei‐Dong Fan, Kuan Liu, Qi Zhong, and Yi‐Ning Huang made critical revisions to the manuscript for important intellectual content. Xian‐Bo Wu revised the conception and design of the study, provided guidance for the statistical analysis. Meng‐Chen Zou assisted in the conception and design of the study and provided final approval of the manuscript version for publication. Xian‐Bo Wu is the guarantor of this work and, as such, had full access to all the data in the study and is responsible for data integrity and data analysis accuracy.This study was supported by the National Natural Science Foundation of China (Grant No. 82173607), the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2021A1515011684), the Open Project of the Guangdong Provincial Key Laboratory of Tropical Disease Research (Grant No. 2020B1212060042), and the Guangzhou Science and Technology Project (Grant No. 202102080597).There are no conflicts of interest to declare.Data S1. Supporting information.Click here for additional data file.


SS) for dairy cows; however, starch digestibility varies greatly depending on source, grain processing, and potentially interactions between these factors. The objective was to study the effects of the interactions between SS, and particle sizes (PS) on ruminal fermentation, nutrient flow, starch digestibility, and lactation performance of dairy cows. Four ruminally cannulated multiparous Holstein cows were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments. Two SS (corn or sorghum) used in this study were either finely or coarsely ground (using a 1- or 4-mm screen sieve). Digesta flow was quantified using the reticular sampling technique, applying the triple-marker method. Data were analyzed using the GLIMMIX procedure of SAS version 9.3 . For ruminal pH, data were analysed with time as repeated measure. There were no interactions between SS and PS on production or intake, flow, and digestibility of nutrients. Dry matter intake was greater for the corn diet compared to the sorghum diet (25.15 vs. 21.98 kg/d), which consequently affected nutrient intake, however, PS did not affect intake. Milk yield was not affected by SS; however, it was greater for cows fed fine grains than cows fed coarser grains (25.32 vs. 23.16 kg/d). Milk fat and milk protein were not affected by SS or PS. Interactions (SS × PS) were observed for ruminal pH, reticular pH, and volatile fatty acids (VFA) concentrations but not for ruminal NH3–N concentration. Ruminal and reticular pH were greater for sorghum when coarsely ground and the total VFA concentration was decreased, compared to coarse corn and fine sorghum; however, coarsely grinding corn did not affect ruminal or reticular pH nor VFA concentration. Acetate concentration was lower for corn when finely ground; however, finely grinding sorghum did not affect acetate. Decreasing PS increased ruminal digestibility of starch (87.18% vs. 83.43%), reduced the flow of starch to the reticulum (0.79 vs. 0.96 kg/d) but decreased neutral detergent fiber digestibility in the rumen (30.23% vs. 34.88%). Although SS were differently affected by processing, the effects of PS on production, intake, flow, and digestibility of nutrients were observed regardless of the SS. Furthermore, the effects of decreasing PS on pH and VFA concentrations were more pronounced in sorghum compared to corn.Cereal grains are the predominant starch source  for lactation dairy cows. SS) result in different particle sizes (PS) distributions and geometric mean particle sizes  in a meta-analysis, consistent with other studies  and grain processing (1 vs. 4 mm) may interact in various animal responses.The experiment was conducted at the Welgevallen Experimental Farm of Stellenbosch University and carried out in accordance with the South African National Standard for the care and use of Animals for Scientific Purpose (SANS 10386: 2008). Animal care and all experimental procedures were approved by the Stellenbosch University’s Research Ethics Committee: Animal Care and Use (REC: ACU) (protocol number: SU-ACUD15-00064).Four multiparous lactating Holstein-Friesian dairy cows  fitted with ruminal cannulas  were used in a 4 × 4 Latin square design experiment with a 2 × 2 factorial arrangement of treatments; two SS (corn or sorghum) either finely or coarsely ground (using a 1- or 4-mm screen sieve). The duration of each experimental period was 16 d, with the first 10 d for adaptation and the last 6 d used for data collection. Because of the small differences between treatments, adaptation periods were shorter than what usually has been recommended . Grant aGMPS) of milled corn and sorghum grains was determined by sieving. The GMPS is the most common method used to compare PS distribution of cereal grains (NGMPS) was calculated, which is based on the smallest dimension of square openings in sieves. Besides particle size distribution, in vitro fermentation conditions were achieved following the procedure of 2 bubbling) including blanks. Rates of starch degradation were computed using the 7 h formula  and geometric distribution of particle sizes  formulated to meet the dietary requirement of lactating dairy cows according to National Research Council  were inserted into the reticulum through the rumen while holding the steel tip of the pump, which was perforated to prevent rumen digesta from flowing into the pump. While in the reticulum the tip of the pump was released, flushed about 3 to 4 times before collecting 1.0-L of reticular digesta. The reticular digesta pH was measured immediately after sampling using a portable pH meter . The 1.0-L of reticular sample of digesta was divided into subsamples as follows: 400 mL reticular digesta for digesta flow analysis and 150 mL for spare, the remaining fluids were discarded. Samples were placed on ice immediately after collection. The 400-mL reticular subsamples from every time point were pooled and held at −20 °C as they were collected to yield a 4.8-L reticular composite samples from each cow in each period. The reticular digesta samples were not filtered/sieved to discard large particles.Rumen content samples were collected from the ventral area of the rumen before the reticular sampling and rumen pH was measured immediately. The rumen content samples were placed in crushed ice immediately after sampling and stored at −20 °C. Fecal samples were collected (approximately 250 g) on the same 3 d as the reticular and rumen sampling per cow, applying the same sampling time schedule. Fecal samples were collected from the rectum or off ground on a concrete floor immediately after defecation, and not mixed with urine. Samples were stored at −20 °C pending further processing. Fecal samples were used to determine the total tract digestibility using uNDF as internal marker and for marker recoveries.MUN) by means of infrared analysis . Body weight (BW) was recorded daily during milking throughout the experiment using the AfiWeigh system . However, only weight recorded from three consecutive days at the beginning and the end of each period was used to calculate the mean BW of cows for each experimental period. To determine the feed intake, feed offered, and orts were recorded daily per cow before morning feeding for the entire experiment. However, only data from days 11 to 16 were used for data analysis. Samples of TMR and orts were collected daily from days 11 to 16, stored at −20 °C until further analysis.Milk yield was automatically recorded at each milking using the AfiMilk dairy farming system  throughout the experiment. Milk samples were collected during morning and afternoon milking for four consecutive days starting from day 13 to 16 of each period. Daily milk sample (40 mL) composites were obtained by pooling morning and afternoon milk samples based on the proportion of milk yield per cow at each milking. Composite milk samples were preserved with broad spectrum microtabs, stored at room temperature, and delivered to a South African National Accreditation System (SANAS) accredited testing laboratory, MilkoLab  for fat, true protein, lactose, somatic cell counts and milk urea nitrogen (LP), reticular small particle (SP), and reticular fluid (liquid) phase (FP) as described by g  for 5 min at 4 °C using a Beckman coulter centrifuge . The supernatant was poured off and defined as the fluid phase and the pellet was defined as the small particle phase. The separated phases were stored at −20 °C until lyophilized. The large particle phase was ground to pass through a 1-mm sieve using a Wiley mill , and the small particle and liquid phase was ground using a coffee grinder. The concentration of Co, Yb, and uNDF determined in the LP and SP and of Co and Yb determined in the FP was used to mix DM from freeze-dried FP, SP, and LP in the correct proportions to reconstitute the reticular true digesta (RTD) flowing out of the rumen based on the triple-marker method of CP), NDF, acid detergent fiber, and uNDF. Pooled rumen contents from each period were thawed at room temperature and subsamples were taken for ruminal volatile fatty acid (VFA) and ammonia (NH3) analyses. Feed, orts, and fecal samples were also thawed at room temperature, pooled per cow over each sampling period, thoroughly mixed by hands and subsampled. Subsamples were dried in a forced air oven at 60 °C for 72 h to determine DM content and ground to pass through a 1-mm sieve using a Wiley mill  pending analysis.Reticular digesta samples, which were pooled by period for each cow, were thawed at room temperature and separated into three different phases: reticular large particle  were added to predigest samples for about 15 min before adding deionized water (2.5 mL). Samples were digested using CEM MARS microwave digester at 210 °C and 800 PSI. Vessels were cooled, and samples were diluted (10-fold) to reduce the acid concentration prior to analysis for Co and Yb. Ruminal VFA concentrations were determined using a gas chromatograph-mass spectrometry , with clean-up procedure of rumen content samples , and a dilution factor of 20.The concentration of uNDF in all TMR samples, digesta fractions  was calculated as 100 − % ash; nonfiber carbohydrates was calculated as 100 −  (% CP + % aNDFom + % EE + % ash) according to the The DM and ash content were determined according to the Nutrient intake was calculated using the amounts and compositions of feed offered and refused. Nutrient flow was calculated using the reconstitution system based on the three markers  using the procedures described by Total-tract nutrient digestibilities were calculated from uNDF as an internal marker and nutrient concentration in the refusals-adjusted diet and feces as described by P ≤ 0.05 and 0.05 < P ≤ 0.10, respectively. Results are reported as least square means and respective standard errors. Post hoc comparisons were performed using Tukey’s test.Production data, nutrient flow, ammonia, and volatile fatty acids and digestibility were analysed using the GLIMMIX procedure of SAS  according to a 4 × 4 Latin square design with 2 × 2 factorial arrangements of treatments, with PS and SS, and their interaction, treated as main fixed effects. The random effect of period and cow were also included in the model. For ruminal pH, data were analysed using the GLIMMIX procedure of SAS  with time as a repeated measure, various covariance structures were tested, and the compound symmetry covariance matrix structure was selected because it resulted in the smallest Bayesian and Akaike information criteria. Statistical significance and trends were considered at −1 (fine corn), 63.5% and 16.8 h−1 (coarse corn), 68.3% and 14.4 h−1 (fine sorghum), 60.1% and 13.1 h−1 (coarse sorghum).Although the statistical analysis of PS distributions and NGMPS of SS was not performed because corn and sorghum came from the same source, the distribution of particles among the different sieves was described, but not compared . At 1-mmP = 0.51) by SS; however, it was greater (P = 0.05) for cows fed fine grains than cows fed coarser grains . Milk fat and milk protein were not affected (P > 0.05) by SS nor by PS. Content of milk lactose was greater (P = 0.05) in cows fed corn than sorghum diets, but the yield of lactose did not differ between SS. However, lactose yield was lower (P = 0.04) in cows fed coarsely than finely ground grains. The MUN was lower for cows fed corn compared to sorghum diets. The ECM was not affected by SS or PS (P = 0.43), but feed efficiency was affected by SS, with greater efficiency for cows fed sorghum diets than corn diets (P = 0.01).The effects of dietary SS and PS on milk yield and composition are presented in P = 0.04), PS (P = 0.04), interaction between SS × PS (P < 0.01), and interaction between PS × time (P = 0.05) were significantly affected by the treatments. No effects were observed for the interactions between SS × time (P = 0.98) and the interaction among SS × PS × time (P = 0.92). For the interaction between SS × PS coarse sorghum had higher pH , PS × time (P = 0.14), and SS × PS × time (P = 0.78). However, a significant effect was observed for SS (P = 0.02), PS (P = 0.01), and the interaction SS × PS  was lower for cows fed corn compared with cows fed sorghum diets (P = 0.05). There was an interaction between SS and PS on acetate, butyrate and isovalerate (P < 0.01) but not on propionate, acetate:propionate, and isobutyrate. Acetate concentration was lower for corn when finely ground, whereas, finely grinding sorghum did not affect acetate. The concentration of ruminal propionate was affected by SS and PS, with greater propionate observed in corn diets (P < 0.01) and finely ground diets (P < 0.01). However, butyrate and isovalerate were greater for finely ground sorghum than corn, as finely griding corn did not increase the levels of butyrate and isovalerate. Acetate to propionate ratios decreased for diets with corn and lower PS (P < 0.01). Lower ruminal concentrations of Isobutyrate was affected by SS, with lower content in the corn diet compared with sorghum diets (P < 0.01).No effect was observed for PS or interaction between SS and SP on the ruminal NHP > 0.05). Compared to sorghum as a SS, cows had greater DM, OM, starch, and NDF intake when fed corn diets (P < 0.05). Intake of nutrients was affected by SS, with greater intake in cows fed corn diets compared with cows fed sorghum diets. The PS had no effect on intake of nutrients (P > 0.05).Treatment effects on intake, flow and digestibility of DM, OM, starch, and NDF are presented in P = 0.04), with greater digestibility in cows fed corn diets compared to cows fed sorghum-based diets. The NDF ruminal digestibility tended to be greater in cows fed sorghum diet (P = 0.07). There was no effect of SS on OM and starch ruminal digestibility. Decreasing PS increased apparent digestibility of starch in the rumen (P = 0.02) but decreased NDF digestibility in the rumen (P = 0.03). The digestibility of DM and OM in the rumen tended (P = 0.09) to be greater for cows fed coarsely ground diet. The flow of DM, OM, and starch was not affected by SS but that of NDF was greater in corn than sorghum-based diets (P = 0.05). Decreasing PS reduced the flow of starch to the reticulum (P = 0.02), increased the DM flow (P = 0.05) and tended to increase OM flow (P = 0.06) but PS had no effect on the flow of NDF to the reticulum.Apparent ruminal digestion of DM was affected by SS (P = 0.02), but it was not affected by SS. Conversely, apparent total-tract NDF digestibility (TTNDFD) was affected by SS (P = 0.04) but not by PS (P > 0.05). Cows fed corn diet had a lower TTNDFD than cows fed sorghum-based diet. The apparent total-tract digestibility of DM and OM were unaffected by SS or by PS (P > 0.10).The apparent total tract digestibility of starch was greater for finely ground diets than coarsely ground diets  this is particularly important for milk production and composition; therefore, readers should interpret the data sensibly; however, the main goal of this study was to evaluate the effects of starch source, particle size, and their interaction on metabolism; milk production and composition were an extra set of information that help us tie together the metabolism data, future studies with greater animal numbers are warranted. Milk yield was affected by PS.It is important to note that this study had a small number of observations  dietary CP content of corn diets compared to the sorghum diets, or it could potentially indicate an improvement in ruminal nitrogen utilization in the corn diets. A greater feed efficiency for cows fed sorghum diets than corn diets could relate to lower DMI.3–N concentration on corn diets could be attributed to increased ruminal starch digestibility thereby reducing the deamination process or improving the microbial capture of released AA or released NH3–N in the rumen. Starch fermentability affects VFA concentration, therefore, the greater concentration of propionate in cows fed fine and corn diets could be because of increased rumen fermentation or possibly a lower absorption as compared to coarse and sorghum diet. Starch in sorghum has a lower digestibility because of a strong starch-protein matrix  but not on the ruminal NH


Transfusion‐related acute lung injury (TRALI) is a serious complication of blood transfusion and can also develop severe hypoxemia. In TRALI cases with difficult blood oxygenation on mechanical ventilation support, temporary veno‐venous extracorporeal membrane oxygenation support appears to maintain oxygen levels. On chest X‐ray, the cardiothoracic ratio (CTR) was 58% with normal lung fields . He was scheduled to receive intraoperative platelet transfusion.A 79‐year‐old man  was scheduled for total cystectomy and ileal conduit diversion for bladder cancer. The patient had a history of acute myeloid leukemia and achieved remission by chemotherapy 9 years earlier. He was diagnosed with a thoracic aortic aneurysm and myocardial infarction, and underwent total arch replacement and coronary artery bypass grafting 3 years earlier. His blood pressure, heart rate, and peripheral blood oxygen saturation  of 0.5, and a large amount of foamy sputum was suctioned from the endotracheal tube. The patient became hypotensive, and noradrenaline administration was initiated. The patient was transfused with packed red blood cells (560 mL), platelets (400 mL), and 5% albumin (1000 mL). The total amount of fluid infusion was 5100 mL; total blood loss was 1552 mL, and total urine volume was 100 mL. Total operation time was 3 h 59 min, and total anesthesia time was 5 h 18 min. The postoperative chest X‐ray showed bilateral pulmonary edema  of 70.1 and was transferred to the intensive care unit (ICU) under sedation and mechanical ventilation. After transfer to the ICU, bleeding from the drainage tube continued, and anemia progressed. Therefore, he was scheduled for emergency hemostasis in the operating room 1 h after admission to the ICU.For anesthesia induction, he received intravenous midazolam 7 mg and remifentanil 0.2 μg/kg/min, and endotracheal intubation was carried out with rocuronium 50 mg as a muscle relaxant. Anesthesia status was maintained using 4% desflurane and remifentanil 0.1–0.2 μg/kg/min. When his blood pressure dropped, ephedrine and/or phenylephrine was administered as needed. Standard intraoperative monitoring and invasive blood pressure measurement were carried out. Platelet transfusion was initiated at the beginning of the surgery, and the blood oxygenation level of the patient gradually decreased 40 min after the transfusion, with SpOa Figure . The pat2 1.0 showed pH 7.06, PaCO2 96.1 mmHg, PaO2 67.9 mmHg, and HCO3–26.1 mmol/L, indicating severe hypoxemia and hypercapnia. VV‐ECMO support was then started.Anesthesia was maintained using desflurane and remifentanil, and continuous administration of sivelestat was added. Steroid was also administered to correct increased vascular permeability. During the operation, foamy secretions were continuously produced from the endotracheal tube and removed using a bronchofiberscope and a suction tube. A recruitment maneuver was also manually carried out whenever necessary. TRALI was suspected from the clinical course. After surgical hemostasis, blood gas analysis at FiO2O, PEEP at 10 cmH2O, and FiO2 at 0.4 was provided. His lung condition improved gradually, and foamy secretions decreased from postoperative day (POD) 2. The chest X‐ray image improved markedly. His further clinical course was good, and he was weaned off VV‐ECMO on POD 6 and mechanical ventilation on POD 7. He was then discharged from the ICU. Antibody testing of donor serum was performed for TRALI diagnosis, and the anti‐HLA Class II antibody was positive, and a positive cross reaction to the patient's white blood cells was confirmed.His chest X‐ray at the beginning of VV‐ECMO support showed infiltration in the entire lung field Figure . He rece32 1.0 was performed during surgery to ensure oxygenation. The present case of TRALI had a good clinical course with systemic organ support by VV‐ECMO in the ICU.The present patient showed reduced blood oxygenation levels after platelet transfusion and foamy endotracheal secretions. Therefore, TRALI was strongly suspected during the surgery. TRALI is characterized by hypoxemia within 6 h after blood transfusion and bilateral lung infiltrations on chest X‐ray.Two underlying mechanisms of TRALI are considered, immunological and non‐immunological mechanisms.There are no established effective medications and/or specific treatments for TRALI, and only supportive and symptomatic therapies are currently given. Although there is a report that steroid was used for TRALI treatment,The present case of TRALI was triggered by intraoperative platelet transfusion and required VV‐ECMO support. Further studies are necessary to elucidate the underlying mechanisms of TRALI, and technical progress in antibody detection methods is needed to prevent TRALI and develop new treatments. Results from large‐scale clinical studies of the intraoperative management of TRALI are needed to improve the clinical outcome of this pathological condition.Yusuke Ishida: Conceptualization; writing – original draft. Koichi Nakazawa: Conceptualization; writing – review and editing. Toshio Itabashi: Conceptualization; writing – original draft. Mikiko Tomino: Conceptualization; writing – review and editing.None.The authors declare that they have no competing interests associated with this manuscript.Not applicable.Written, informed consent was obtained from the patient for publication of this case report and the accompanying images.


To identify the potential diagnostic biomarkers of rheumatoid arthritis (RA) and assess the relation between visuospatial dysfunction and disease activity in RA patients using mental rotation task (MRT)-based functional magnetic resonance imaging (fMRI).A total of 27 RA patients  and 27 well-matched controls were enrolled. The visuospatial function of the subjects was measured by MRT. Brain activity data were collected using blood oxygen level dependent fMRI technique under MRT. Disease activity score 28 (DAS28) was used to evaluate the disease severity of RA patients. An analysis of the correlations between abnormal visuospatial-related brain regions, MRT performance, and DAS28 was conducted.r = −0.621, p = 0.01) and positively correlated with DAS28 , and MRT accuracy was negatively correlated with DAS28 in RA patients .RA patients performed worse on MRT than controls. Compared to the control group, RA patients showed enhanced activation in the left precuneus, left superior frontal gyrus and right cingulate gyrus during the rotation task, with left hemisphere dominance. RA patients in active showed enhanced activation in the left precuneus, left middle frontal gyrus and right cingulate gyrus compared to the patients in remission. The left precuneus activation was negatively correlated with MRT accuracy (Enhanced activation of the left precuneus in RA patients affects visuospatial function and is closely related to disease activity. These changes may provide a valuable diagnostic neuroimaging biomarker of RA. Rheumatoid arthritis (RA) is a chronic multi-system inflammatory disease, and its typical clinical symptoms are symmetric multiple arthritis, mainly involving small joints . The gloBartolini et al. found that visuospatial tasks were impaired and highly correlated with disease activity in 71% of RA patients . Shin etWe hypothesized that there existed brain functional changes associated with disease activity and that could serve as neuroimaging biomarker of cognitive impairment in RA patients. Herein we used mental rotation task-based fMRI combined with psychological scales to investigate visuospatial cognitive function in RA patients and further explore whether the changes in brain functional characteristics are associated with disease activity of RA.In this cross-sectional study, 29 female patients with RA were recruited from the Department of Rheumatology, the First Affiliated Hospital of Shantou University Medical College, during the period of December 2019 to April 2021. Among the RA patients, 2 were excluded due to excessive head motion. Inclusion criteria for the RA group were as follows: meeting the 2010 American College of Rheumatology and European Alliance Against Rheumatology (ACR/EULAR) classification criteria for rheumatoid arthritis , ages beThis study was approved by the Ethics Committee of the First Affiliated Hospital of Shantou University Medical College (B-2021-237). All participants gave written informed consent.Cognitive functions were assessed by the Montreal Cognitive Assessment (MoCA), which includes visuospatial/executive, naming, attention, language, abstraction, delayed recall and orientation subtests. People are considered to have normal cognitive function if the score is ≥ 26, mild cognitive impairment if < 26, and dementia if ≤ 19 . The HosThe block-designed MRT was programmed and presented using E-Prime 3.0 software . The 3D graphics, designed by Shepard and Metzler , were prThere were four epochs in an fMRI scan. Each epoch consisted of a fixation block (a screen with a fixation cross lasting 30 s), a comparison block and a rotation block. Each task block included 12 trials, each of which contained a baseline condition (a screen with a center fixation presented for 0.5 s), and a task-related stimulus (presented for 6.5 s). So, the total experimental duration was 13 min and 12 s. The experimental procedure is shown in Fig. All participants were given instructions and training session before the fMRI scan. The E-Prime and stimulus presentation goggles system  were used to present the stimulus. MRT was performed synchronously during the MRI scan, and the accuracy and response time were recorded by E-prime.2, 244 slices, slice thickness = 1.3 mm, and no gap.Imaging data were acquired using a 1.5 T MR scanner  and a standard GE head coil in the Department of Radiology, the First Affiliated Hospital of Shantou University Medical College. Headphones and earplugs were provided to shield background noise. BOLD-fMRI acquisition used an echo-planar imaging sequence with the following parameters: repetition time (TR) = 3000 ms, echo time (TE) = 45 ms, flip angle (FA) = 90°, imaging matrix = 64 × 64, 20 slices, field of view (FOV) = 250 mm × 200 mm, slice thickness = 6.0 mm, no gap. Slices were acquired in an interleaved method in order to avoid crosstalk between adjacent slices. Anatomical T1-weighted fast spoiled gradient recalled (FSPGR) image parameters: TR = 1.6 ms, TE = 5.1 ms, FA = 20°, matrix = 256 × 256, FOV = 256 × 256 mmhttp://afni.nimh.nih.gov/afni/). The first 2 time-points of the fMRI images were removed. Preprocessing steps included slice timing correction, head motion correction, spatial smoothing (FWHM = 6 mm) and spatial normalization to standard coordinates of the Talairach and Tournoux atlas. Participants who had obvious head movements (motion > 2 mm or rotation > 2°) during scanning were excluded. A general linear model (GLM), with covariates of six motion, was used to model task-related effects in first-level individual analysis. We treated the fixation conditions as baseline and deconvolved two task-related regressors with the canonical hemodynamic response function (HRF).We analyzed fMRI data using the Analysis of Functional NeuroImages (AFNI), which can preprocess, analyze, and display fMRI data . A cluster size correction (20 voxels) was applied calculated from the 3dClustSim of AFNI on data initial threshold, voxel size of the analysis space was 3 × 3 × 3 mm3.A 2 × 2 factorial design analysis of variance (ANOVA) was designed for fMRI analyses, with the group (RA and HC group) and task (rotation and comparison) as factors. The differences of activation were analyzed for the main effect and simple effect of the group, task and the interaction effects of group by task. Statistical threshold was set as p < 0.05 (two tailed). Continuous variables were expressed as mean ± standard deviation. Statistical analysis was performed with Statistical Package for the Social Sciences (SPSS) version26 for Windows .The independent-samples t test was used to compare age, duration of education, and performance of neuropsychological tests between two groups. For accuracy and response time in the mental rotation task, a 2 × 2 factorial design ANOVA was used to investigate the main effect and interaction effect; an independent-samples t test was used between groups, and a paired t test was used within a group. Pearson correlation analysis was used to investigate the relationship among the ROIs of the activated brain region in a rotation task , clinical and MRT data. Differences were considered statistically significant if p < 0.001). The scores of visuospatial/executive, naming, attention, language, abstraction and delayed recall in the RA group were lower than those of HCs . Both scores of anxiety and depression in the RA group were higher than that of HCs , while RA patients did not meet the positive criteria of clinical anxiety/depression.Demographic, clinical and neuropsychological data of all participants are shown in Table F = 0.243, p = 0.623) for response time, while the main effect of task  = 66.012, p < 0.001) and main effect of group  = 8.234, p < 0.001) were observed, with the rotation response time longer than the comparison response time. The interaction effect of group by task for accuracy  = 33.58, p < 0.001) was detected, as well as the main effect of group  = 194.29, p < 0.001) and task  = 49.388, p < 0.001) for accuracy. Furthermore, the accuracy of RA patients was lower than that of HCs both in the comparison task  and the rotation task . As for RA patients, the rotation accuracy was lower than comparison accuracy , but no difference was found in the control group .MRT accuracy and response time of RA and HC groups are summarized in Table There was significant interaction effect of group by task in the right inferior parietal gyrus, bilateral precuneus and right middle frontal gyrus Fig. a. For thr = −0.621, p = 0.01) and positively correlated with the DAS28-CRP score  and DAS28-ESR score . Accuracy of MRT was negatively correlated with the DAS28-CRP score  and DAS28-ESR score  .We chose the left precuneus (L-PCUN), left superior frontal gyrus and right cingulate gyrus as regions of interest (ROIs). L-PCUN activation during the rotation task was negatively correlated with MRT accuracy  . As an iUnder the MRT, both groups showed bilateral activations in the occipital–parietal–frontal network, which is consistent with previous research , and theCompared to HCs, RA patients showed enhanced activation in the posterior parietal cortex , superior frontal gyrus and cingulate gyrus. These activated brain regions are involved in visuospatial cognitive processing, especially the posterior parietal cortex and superior parietal lobule, which have been shown proved to be the main brain regions involved in visuospatial cognition , 25. WitRA patients performed poorly in behavioral visuospatial tasks, but in the mental rotation task, the bilateral posterior parietal cortex and dorsolateral prefrontal cortex were not only activated, but left hemisphere dominance was shown, contradicting the right hemisphere dominance in visuospatial cognition . We hypoMoreover, the left precuneus showed enhanced activation in patients with active RA, compared to those in remission. Studies have shown that disease activity is associated with cognitive impairment in RA patients, and it is considered necessary to timely adjust the treatment plan of RA patients through DAS28 monitoring , 33. OurThe results of this study should also be considered in light of some limitations. First, the sample size of this study is relatively limited. By increasing the sample size, future studies could be examined the other potential confounding factors such as HB levels, high depression and anxiety scores. Furthermore, steroids and disease modifying anti-rheumatoid drugs in medications of RA are major influence factors in cognition function. Therefore, future studies should take these factors into account to reveal the effects of medication on cognitive dysfunction in patients with RA, which could provide meaningful guidance for clinical treatment. In this way, the mechanism of cognitive impairment in patients with RA will be clearer, which can also provide more precise guidance for the prevention and treatment of cognitive impairment in RA.In conclusion, the left precuneus is a neuroimaging biomarker of visuospatial dysfunction in RA patients. Enhanced activation of the left precuneus is strongly associated with disease activity of RA patients, which suggests the left precuneus may be an objective radiographic indicator for assessing disease severity in patients with RA. The brain functional MRI provides a valuable imaging evaluation index that can be used to evaluate the progression and potential pathogenesis of RA.


Displaced abomasum (DA) is one of the most important metabolic disorders of dairy cattle. In DA, ischaemic damage may occur as a result of impaired perfusion due to abomasal displacement, which may result in gastrointestinal mucosal damage.Investigation of gastrointestinal tissue damage in cattle with right displacement of the abomasum (RDA) and left displacement of the abomasum (LDA) using intestinal‐related biomarkers.Forty‐eight DA  and 15 healthy Holstein dairy cows were enrolled between March 2021 and July 2022. Serum biomarkers including gamma‐enteric smooth muscle actin (ACTG‐2), liver‐fatty acid binding proteins (L‐FABP), platelet activating factor (PAF), trefoil factor‐3 (TFF‐3), leptin, claudin‐3 and interleukin‐8 (IL‐8) concentrations were measured from venous blood samples.L‐FABP concentrations in the LDA group and TFF‐3 concentrations in the RDA group were lower than in the control group. The leptin concentration of the RDA group was higher than that of the other groups. There was a negative correlation between lactate, leptin and IL‐8 concentrations. There was a negative correlation between lactate and TFF‐3, whereas leptin and lactate were positively correlated. Leptin was the more reliable biomarker for discriminating between RDA and LDA cases.Changes in serum L‐FABP, TFF‐3 and leptin concentrations in cattle with DA may reflect acute intestinal injury and the subsequent repair phase. However, these biomarkers had poor diagnostic performance in discriminating between healthy and cattle with DA, while leptin emerged as the most useful marker in differentiating LDA from RDA cases. In this study, intestinal injury‐related biomarkers were evaluated in serum samples from dairy cows with displaced abomasum (DA). Serum fatty acid binding proteins, trefoil factor‐3 and leptin concentrations in cattle with DA indicate that intestinal damage develops in DA cases and the repair phase is activated against this damage. All cows with DA were within 2–4 weeks of postpartum, and 80% of the animals were in their third and fourth lactations.Both general condition and initial clinical signs of RDA cows were similar to those of LDA cows. The history of cows with DA included loss of appetite, decreased rumen motility and rumination and inadequate defecation with a sudden decrease in milk yield. No signs of pain were observed in cows with DA except for two cows with RDA. Rectal examination results were unremarkable. The duration of the symptoms ranged from 2 to 5 days . Although these farms have different feed management practices, they do not use a post‐fresh diet  formulation that contains less than 21% neutral detergent fibre (NDF) from the feed.2.1.2Cows with DA underwent a complete physical examination (conducted by MI and AE with the same protocol). The diagnosis of DA was based on the presence of a characteristic ping sound on simultaneous auscultation and percussion from both sides of the abdomen and a splashing sound on the abdominal ballotoment. Ultrasonography was performed to confirm the diagnosis of DA and the location of the abomasum (LDA or RDA) using a Mindray DC‐6 Vet, China. In case of suspicion, a Liptak test was performed by inserting a needle into the viscera to remove fluid and measuring the pH of the fluid to confirm its acidic (pH < 4) character  other than DA were not included in the study. Animals in all experimental groups were evaluated by vaginal discharge and uterine palpation to exclude metritis and retention. To exclude ketosis, blood concentrations of betahydroxybutyrate (BHB) ≥ 1.2 mmol/L were considered Oetzel, . In addi2.2The control group consisted of 15 healthy Holstein cows, similar to the DA group, at the same postpartum (2–4 weeks) and lactation (3rd or 4th) period, selected from our faculty farm. Healthy cows were defined as not treated for disease by the farm veterinarian. Control cows underwent a complete physical examination and haematological analysis to ensure that they were healthy prior to inclusion in the study. No abnormalities were found during the physical examination and haematological analysis.2.33EDTA and non‐anticoagulant tubes were used for blood gas, complete blood count (CBC) and serum collection, respectively. Blood gas and CBC were performed within 5–10 min. Blood gas and electrolyte analysis included power of hydrogen (pH), partial pressure of carbon dioxide (pCO2), partial pressure of oxygen (pO2), potassium (K), sodium (Na), calcium (Ca), chlorine (Cl), glucose (Glu), lactate (Lac), base excess (BE), and bicarbonate (HCO3) were measured using an automated blood gas/electrolyte analyser . Complete blood count parameters including total leukocytes (WBC), lymphocytes (Lym), monocytes (Mon), granulocytes (Gra), erythrocytes (RBC), haematocrit (Hct), haemoglobin (Hb) and platelets (PLT) were measured using an automated cell counter . Blood samples for biomarker analysis were kept at room temperature for 15 min, centrifuged at 2000 × g for 10 min, serum extracted and stored at −80°C until the day of analysis.Blood samples of 10 mL were collected from all cattle by jugular venipuncture at the time of admission. Plastic syringes containing sodium heparin, tubes containing K2.4Serum concentrations of ACTG‐2, L‐FABP, PAF, TFF‐3, leptin, claudin‐3 and IL‐8 were measured using commercially available bovine‐specific ELISA kits  according to the manufacturer's instructions. The intra‐assay coefficient, inter‐assay coefficient and minimum detection concentration were ≤ 5.5–6.4%, ≤ 6.7–7.9% and 0.1 μg/mL for ACTG‐2; ≤ 15%, ≤ 15% and 0. 05 ng/mL for L‐FABP; ≤ 8%, ≤ 12% and 12 pg/mL for PAF; ≤ 5.9%, ≤ 7.1% and <0.26 ng/mL for TFF‐3; ≤ 8%, ≤ 8% and 0.188 ng/mL for LP; ≤ 8%, ≤ 8% and < 0.188 ng/mL for claudin‐3; ≤ 8%, ≤ 12% and 5 pg/mL for IL‐8.2.5p value (< 0.05), sensitivity, specificity (>70%) and observed power . Thresholds for selected ROC parameters were determined in accordance with previous reports to suggest the ability of the test to discriminate between patients with and without disease or condition. For this purpose, it was accepted that an AUC of 0.500 suggests no discrimination, 0.600 to 0.700 suggests poor discrimination, 0.700 to 0.800 is considered acceptable, 0.800 to 0.900 is considered excellent, and more than 0.900 is considered excellent  was used to evaluate the data. The Kolmogorov–Smirnov test was used to determine the normality of the variables and the homogeneity of the variances. Parametric data were expressed as mean ± SD and evaluated by one‐way analysis of variance (ANOVA) followed by post hoc Tukey's test. Non‐parametric data  were expressed as median (minimum/maximum) and evaluated using the Kruskal–Wallis test. The Spearman's rank test was used to investigate possible correlations between parameters. Receiver operating characteristic curve (ROC) analysis was used to determine the optimal diagnostic cut‐off values to assess the presence of gastrointestinal damage and to investigate the importance of these biomarkers in differentiating the extent of damage in cases of LDA, RDA and DA. The observed power (Op or post hoc power) was obtained by performing univariate general linear model analysis using the same statistical software. The diagnostic performance of the biomarkers was evaluated using parameters including area under the curve , 33.1p < 0.05). In the CBC analyses, WBC, Lym, Htc and Hb levels were higher in the LDA and RDA groups, while PLT levels were lower than in the control group (p < 0.05).The results of blood gas and CBC analyses are presented in Table 3.2p < 0.05). The serum TFF‐3 concentration of the RDA group was lower than that of the control group, while the leptin concentration was found to be higher (p < 0.05). In addition, the serum leptin concentration of the RDA group was higher than that of the LDA group (p < 0.05).The results of the biomarker analyses are shown in Table 3.3The results of the correlation analysis are shown in Table 3.4p < 0.001), with 100% sensitivity and 66.7% specificity was the best biomarker for discriminating between cattle with LDA and RDA (Table p < 0.001), with 80% sensitivity and 50% specificity and TFF‐3 concentration at the cut‐off point of 8. 02 ng/mL, area under the curve (AUC) 0.672  0.521–0.822; p < 0.001), with 80% sensitivity and 54.2% specificity, have a poor diagnostic discrimination performance for differentiating between healthy cattle and cattle with DA  0.864  0.758–0.970; DA Table . FurtherDA Table .4In this study, intestinal injury‐related biomarkers such as ACTG‐2, L‐FABP, PAF, TFF‐3, leptin, claudin‐3 and IL‐8 were evaluated in serum samples from dairy cows with DA. It was found that serum concentrations of leptin, L‐FABP and TFF‐3 could provide useful information in the evaluation of clinical‐pathological changes in DA.Because there are limited studies evaluating intestinal injury in veterinary medicine, the results of this study are discussed in the context of studies conducted in both human and veterinary medicine. Biomarkers related to gastrointestinal injury play a role in the presence of damage, protection and/or repair processes of the gastrointestinal tract  alterations occur in the functions of membranous ion transport system (Ng et al., Although we attempted to match control and ill animals for factors such as age, diet, parity and duration of illness, these animals were admitted to our hospital from different farms, which may have affected biomarker concentrations. A small study population resulted from this standardisation effort. In addition, the lack of histopathological confirmation of intestinal damage with biomarkers is one of the limitations of this study. All these issues deserve to be addressed in further studies.5In conclusion, alterations in serum liver‐fatty acid binding proteins, trefoil factor‐3 and leptin concentrations in cattle with DA indicate that intestinal damage develops in DA cases and the repair phase is activated against this damage. However, these biomarkers had poor diagnostic performance in discriminating between healthy and cattle with DA, while leptin emerged as the most useful marker in differentiating LDA from RDA cases.Conceptualisation: Ider M, Ok M, Yildiz R. Data curation: Alkan F, Erturk A, Durgut MK, Sulu K. Formal analysis: Ider M, Naseri A, Erturk A, Durgut MK, Yildiz R. Funding acquisition: Ider M, Erturk A, Durgut MK. Investigation: Ider M, Ok M, Erturk A, Yildiz R, Gülersoy E. Methodology: Ider M, Erturk A, Durgut MK. Project administration: Ider M, Erturk A, Durgut MK. Resources: Ider M, Ok M, Yildiz R. Software: Ider M, Naseri A, Ok M, Erturk A, Gülersoy E. Supervision: Ider M, Ok M, Yildiz R. Validation: Alkan F, Erturk A, Durgut MK, Sulu K. Visualisation: Erturk A, Durgut MK. Writing – original draft: Ider M, Naseri A, Erturk A, Durgut MK. Writing – review & editing: Ider M, Naseri A, Ok M, Erturk A, Gülersoy E.The authors declare no conflicts of interest.None.The study was conducted with the approval of the Selcuk University Veterinary Faculty Experimental Animal Production and Research Center Ethics Committee with decision number 2021/97.


To examine the associations between self‐efficacy, resilience and healthy ageing among older people who have an acute hospital admission.A cross‐sectional study.Survey and medical record data were collected from older people on discharge from hospital. The survey measured self‐efficacy with the 6‐item General Self‐Efficacy scale (GSE‐6), resilience with the Brief Resilience Scale (BRS), and healthy ageing with the Selfie Ageing Index (SAI). Medical record data included potential confounders: co‐morbidities, frailty items, previous falls and previous admission in the last 28 days. Multi‐linear regression and Spearman's rank correlation coefficient were used to examine the independent associations between self‐efficacy, resilience and healthy ageing.ß = ‐0.08, p = 0.001) remained negatively associated with healthy ageing, while self‐efficacy  and resilience  remained positively associated with healthy ageing (R2 = 0.243). Positive correlations were found between self‐efficacy , resilience  and healthy ageing. Positive correlations were also found between self‐efficacy and resilience . Those with lower self‐efficacy and resilience were more likely to report reduced activities of daily living, mobility, physical activity and mood.Responses were received from 143 older people (mean age 79). After adjusting for potential confounders, co‐morbidities (Findings indicate that while the number of co‐morbidities have negative consequences for healthy ageing among older people who are hospitalised, the promotion of self‐efficacy and resilience can potentially contribute to healthy ageing within the physical and psychological domains.Nurses can promote self‐efficacy, which can potentially increase resilience and help to improve self‐management of chronic conditions, functional ability in daily activities, mobility and physical activity and reduce both anxiety and depressive symptoms.Participant feedback throughout the data collection process assisted in the evaluation of study methods and data interpretation. This included processes such as assessing selected tools and clarifying the meanings of healthy ageing factors. A subsequent qualitative phase collected disparate data and so was reported separately (Authors Own).3.2Participants were recruited from the acute wards of three public hospitals in Sydney, Australia. The hospitals span two metropolitan and one rural local government area that fall within one local health district. The two metropolitan government areas serve communities with high migrant populations and areas of socioeconomic disadvantage, while the rural government area has 24.7% of the community aged over 65 years .Power was calculated using the average acute admission rates over a 3‐month period in the previous year, of people aged 65 or greater across the included hospitals. It determined a minimum of 100 participants were needed to give a power of at least 0.83 to detect a moderate correlation between healthy ageing, self‐efficacy and resilience  Registered Nurses with specialist aged care qualifications. People were excluded if they were discharged to a residential aged care facility, supported accommodation or were considered terminally ill.3.5Data were collected between February and May 2021. Potential participants were identified in consultation with nurse managers and invited to participate on either the day of or the day before their discharge. Time of discharge was selected to accurately measure participant's levels of self‐efficacy and resilience when being discharged home, and after experiencing hospitalisation. While ideally data were to be collected on the day of discharge, this was not always practical. Therefore, where this could not be achieved data were collected the day before a known discharge. Participants were asked to complete the survey either independently using a tablet device provided by the researcher or by verbally responding to questions with the researcher entering their responses.3.63.6.1The survey was developed using tools that had been previously validated and widely used in research with older people and based on relevant literature   to measure resilience, that is the ability to recover from a stressor   data included coded medical record data from current and previous admissions. Data collected from the survey were linked to data collected from the HIE database using participants' medical record numbers and hospital sites, which were recorded at the beginning of the survey. Extracted data included age, gender, number of co‐morbidities, previously recorded falls, number of frailty deficit items, hospital length of stay and hospital admissions within the previous 28 days.3.7All included tools were chosen for their high internal consistency. The validity of the SAI was demonstrated through its predictive value of the probability of having a doctor's visit, having depression, the number of doctor visits and the number of chronic conditions  of the multi‐linear regression models is presented to estimate the variability of SAI explained by the variables included in the models. As the rate of missing data was <0.001%, no data imputation was undertaken. The chi‐square test for trend in proportions was used to assess significant trends between self‐efficacy and resilience score quartiles and dichotomised SAI items. This method was adopted to identify potentially modifiable factors of healthy ageing that may be improved through the promotion of self‐efficacy and resilience.All data management and analysis were undertaken using R, version 1.4.1 . Participants were provided with an information sheet outlining the study details, including participant rights to decline, withdraw or participate without impacting on the care received. Consent was obtained from all participants before data collection.44.1n = 85) were female, and the mean age was 79 years (SD 8.4) (Table n = 74) of participants self‐rated their health as fair, while 30.1% (n = 43) rated their health as good/very good/excellent. Overall, 52% (n = 74) of participants had one or more co‐morbidities. There were 26 participants (18.2%) with a previous fall recorded. The average length of stay in the current admission was 5 days (IQR 3–10), and 19.6% of participants (n = 28) had another admission within the previous 28 days. The overall mean scores were SAI 0.59 , GSE‐6 19.3 , and BRS 3.71 . There were no statistically significant differences between scores among the different age groups.Of the 143 participants, 59.4% , and between resilience and healthy ageing . A positive correlation was also found between general self‐efficacy and resilience .The Spearman's rank correlation showed a positive correlation between self‐efficacy and healthy ageing (4.3p = 0.03), undertaking moderate physical activity once or less than once a week (p = 0.01), feeling depressed (p = 0.01), feeling nervous (p = 0.01) and lacking energy (p = 0.1). Similarly, those with lower resilience were significantly more likely to report deficits in ADLs (p = 0.07), mobility difficulties indoors (p = 0.01), undertaking moderate physical activity once or less than once a week (p = 0.03), feeling depressed (p < 0.001), feeling nervous (p < 0.001) and lacking energy (p = 0.02).Tables 4.4ß = ‐0.08; CI 95% ‐0.12, −0.03, p = 0.001), followed by resilience  and self‐efficacy  (Table R2) for this final model was 0.243.After adjusting for age, sex, previously recorded falls, frailty items, number of co‐morbidities and having an admission in the last 28 days, the most significant contributor to healthy ageing was the number of co‐morbidities (5) Table . The coe5This study investigated the associations between self‐efficacy, resilience and healthy ageing among older people who have had an acute hospital admission. The results confirm that co‐morbidities negatively contribute to healthy ageing among older people who have an acute admission, while greater self‐efficacy and resilience positively contribute to healthy ageing. Self‐efficacy was also positively associated with resilience, supporting previous literature identifying self‐efficacy as a key determinant of resilience  declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.Research Ethics Committee approval was obtained from the South Western Sydney Local Health District Human Research Ethics Committee .The authors have ensured that our submission conforms as applicable to the Journal's statistical guidelines. Author Steven Frost has extensive experience in statistical analysis and has consulted with author Sarah Remm in all statistical analyses and reporting of data within this manuscript. The authors affirm that the methods used in the data analyses, which include multi‐linear regression and Spearman's rank correlation, are suitably applied to the study's data within the study design and context, and that statistical findings have been implemented and interpreted correctly.