To assess and characterize neovascularization of the optic disc (NVD) using optical coherence tomography angiography (OCTA) and different OCTA-based methods.This retrospective, observational study included patients who were suspected of having early PDR with no presence of clinically apparent neovascularization (NV) bur were clinically diagnosed with proliferative diabetic retinopathy (PDR), or severe NPDR. Patients underwent standard clinical examinations and OCTA imaging using a 6 × 6 montage scan. Two trained graders identified NVD using different imaging systems (ultra-widefield-colour fundus photography (UWF-CFP), OCT, OCTA and fluorescein angiography (FA)). Moreover, morphological classification of NVD was performed. The detection and morphological classification of NVD by different OCTA-based methods  were compared.P < 0.05). According to its characteristics on OCTA, NVD was divided into four types . For type I, B-scan OCTA exhibited a higher diagnostic sensitivity than other methods (P < 0.05). For types II and IV, there were no statistically significant differences in the sensitivity of various methods between the two groups (P > 0.05).A total of 169 eyes (126 eyes with PDR and 43 eyes with severe NPDR) of 123 participants were included in this study. The detection rate of NVD was 34.91% by UWF-CFP compared with 59.76% by OCT, 59.76% by OCTA, and 62.72% by FA. After excluding 2 cases with epiretinal membranes, the NVD diagnosis detected by OCT was used as the standard. Among 99 eyes diagnosed with NVD by OCT, B-scan OCTA detected NVD with a sensitivity of 97.98%, which was higher than that by en face OCTA (80.81%), VRI Angio (65.66%), and VRI Structure (61.62%) (all OCTA and different OCTA-based methods are significant to the diagnosis of NVD, and the diagnostic accuracy of different detection methods may be related to different types of NVD. Neovascularization of the optic disc (NVD) refers to the formation of new blood vessels in the optic disc, which frequently occurs among patients with proliferative diabetic retinopathy (PDR). It is one of the main causes of severe vision loss. According to previously reported findings, patients with PDR and NVD are at a significant risk of vision loss. NVD accounts for 85% of PDR haemorrhages. Half of PDR patients with untreated NVD become blind within 3 years after the initial diagnosis . As a reDiagnosing PDR is sometimes a major challenge. To our knowledge, slit-lamp fundus biomicroscopy has a low sensitivity for differentiating neovascularization (NV) from intraretinal microvascular abnormalities (IRMAs) . SmallerColour fundus photography (CFP) and fluorescein angiography (FA) were previously used to assess patients at different stages of diabetic retinopathy (DR) and to further plan patient treatment. Ultra-widefield (UWF)-CFP is associated with some deficiencies, such as the inability to differentiate pseudo-colours, peripheral distortion, and reduced resolution. Additionally, CFP cannot distinguish nonperfusion areas (NPAs) from NV areas, and differentiating IRMAs from NV is challenging –8. FA isOptical coherence tomography angiography (OCTA) has facilitated non-invasive imaging of retinal and choroidal microvasculature abnormalities associated with DR, including MAs , NPAs 1, IRMAs , NV 14]14] and cSeveral recent studies have proven the effectiveness of identifying NV via SS-OCTA vitreoretinal interface (VRI) slab images, which capture extraretinal lesions extending into the vitreous , 17. Lu To date, numerous studies have concentrated on the categorization of NVD based on OCTA. Khalid H et al.  classifiThis prospective, observational study was conducted in the Department of Ophthalmology at Shanghai Sixth People’s Hospital from January 2010 to June 2021. Patients who were suspected of having early PDR with no presence of clinically apparent NV but were clinically diagnosed with PDR (either naïve or previously treated) or severe NPDR. Exclusion criteria included eyes with concomitant chorioretinal diseases, glaucoma and severe media opacities, which interfered with image acquisition; poor image quality that prevented the device from automatically creating montage images; or image quality that was otherwise determined to be insufficient for clinical assessment .The study was approved by the Institutional Review Board of Shanghai Sixth People’s Hospital. All protocols were in accordance with the principles of the Helsinki Declaration, and written informed consent was obtained from the patients prior to their participation in the study.All included participants underwent ophthalmic examinations, which included obtaining a medical history  determining visual acuity, slit lamp biomicroscopy of the anterior segment, ophthalmoscopy of the posterior segment, and wide-field colour fundus imaging using the Optos camera , FA system , and OCT/OCTA system (Heidelberg Engineering GmbH). UWF-CFP, FA, and OCT/OCTA were performed on the same day or within 1 week.OCTA scans were conducted out using the OCT/OCTA system (Heidelberg Engineering GmbH). A laser with a central wavelength of approximately 870 nm was used in the OCT/OCTA system (Heidelberg Engineering GmbH) at a scan rate of 85,000 A-scans/s.Regarding the scanning protocol in our clinic, for each patient, a high-definition 6-mm line scan and a 6*6-mm volume scan that were centred on the optic nerve head were acquired (FOV of 20*20°). Each 6*6 mm volume had 512 A-scans per B-scan (with a space of 24 mm between adjacent A-scans) and 512 B-scan positions per volume scan (with a space of 11 mm between adjacent B-scans); OCTA images were acquired using two replicated B-scans at each B-scan spot. It took at least 12 s to obtain a single 6*6 mm volume. Professional ophthalmic photographers performed all OCTA scans, and in necessary cases, they replicated the acquired images several times to ensure that high-quality photographs of high-intensity OCT signals and minimum motion artefacts were captured. The quality scores of scans were expressed as a signal-to-noise ratio (SNR) in decibels (dB) on a scale of 1  to 40 , and the included scans had a score > 20 dB, which was considered good quality. The FA photographs were acquired using the Heidelberg Spectralis HRA + OCT system (Heidelberg Engineering GmbH).NVD was detected using the following methods: (1) biomicroscopy or CFP showed the presence of clearly formed NVD; (2) structural OCT displayed the presence of PRHM; and (3) with the presence of PRHM on structural OCT, an OCTA scan was conducted in that location. A diagnosis of NV was made if a flow signal was evident on the B-scan OCTA or a clear NVE could be observed on the en face OCTA; (4) the presence of leakage on FA was recorded.Two qualified ophthalmologists (CX and LTT) independently examined the OCT, OCTA, and FA images for the presence of NVD, as shown on each imaging mode. Thorough examination of individual OCT B-scans within the volume for the OCT posterior pole revealed the existence of any PRHM. The built-in software of OCTA was employed to distinguish each B-scan mode in the 6*6 mm scanning area. First, a B-scan with PRHM detected an internal blood flow signal, or a clear NVE could be observed on en face OCTA. Then, the en face OCTA images of the superficial retinal slab and vitreoretinal slab were examined for obvious delineation of the retinal neovascular network. The VRI slab was defined with an inner boundary of 100 µm above the ILM and an outer boundary at the ILM. Then, the VRI Structure and VRI Angio were utilized to indicate whether any new blood vessels could be generated . Normally distributed continuous variables are presented as the means ± SD. Differences in NVD detection rates among different groups were compared using the McNemar’s test or the exact McNemar’s test. For all tests, a A total of 123 patients with 169 eyes  were included. It was estimated that each participant had diabetes for an average of 19.2 ± 8.5 years. The median age of the participants was 54.36 ± 17.68 years old. In addition, 82% of patients had type 2 diabetes mellitus. At the time of imaging, 105 eyes (62.13%) were untreated. Twelve eyes with PDR and 17 eyes with severe NPDR were treated with PRP, 13 eyes with PDR and 7 eyes with severe NPDR were treated with PRP and intravitreal injection, and 15 eyes with PDR were treated with vitrectomy.The detection rate of NVD was 34.91% by UWF-CFP compared with 59.76% by OCT, 59.76% by OCTA, and 62.72% by FA. Moreover, 5 NVE lesions were detected on UWF-FA. These lesions were not observed to perforate the ILM by B-scan and were diagnosed as leaky IRMAs.P < 0.05, Table P < 0.05), and the difference was not statistically significant .Two epiretinal membranes were excised from 101 eyes with PRHM, which were identified via structural OCT. Among the remaining 99 eyes, 97 eyes were detected with a flow signal on the B-scan OCTA and a clear NVD on en face OCTA was found in 80 eyes. Additionally, 65 NVD eyes were identified through VRI Angio, and 61 NVD eyes were identified through VRI Structure. The diagnosis of NVD by structural OCT was used as the standard. Among the 99 eyes, B-scan OCTA detected NV with a sensitivity of 97.98%, which was higher than the detection rate by en face OCTA (80.81%), VRI Angio (65.66%), and VRI Structure (61.62%) (P > 0.05) (Table P < 0.05), and the difference between B-scan OCTA and en face OCTA was not statistically significant . For type IV NVD, there was no significant difference in the sensitivity between methods  . For type II NVD, there was no statistically significant difference in the sensitivity between the different methods  is attached or detached. It has been proven that structural OCT and B-scan OCTA provides the highest detection rate for NV. More recently, OCTA has been shown to identify the vascular structure of NVD by the presence of blood flow signals in en-face OCT angiograms –24.NVD imaging requires segmentation of the retina. To identify NVD, optimized vitreoretinal segmentation procedures may cause OCTA to become an even more successful and non-invasive imaging technique . VolumetDifferent anatomical subtypes of NVD observed by OCT can explain the decreased detection rate by various methods. Type I NVD encompasses the physiological cup, and it is thus not raised above the disc surface, making it difficult to identify clinically. Similarly, type II NVD, appearing on the B-scan as tiny buds, may be misdiagnosed clinically as dots of haemorrhage. These two types are difficult to detect by en face OCTA Fig. . To our The present study had a number of shortcomings. First, this was a retrospective study, in which OCTA was compared with clinical examinations. Each patient was examined by an experienced ophthalmologist who confirmed the diagnosis. In addition, although two graders assessed imaging findings, only one senior clinician made the clinical diagnosis for each case. Another shortcoming was that we used the 6*6 scan area. Although the scan range was not wide-angle and was restricted, this study mainly diagnosed NVDs, and the detection of NVE lesions was not performed in other surrounding areas.Finally, the signals on the VRI slabs were evaluated subjectively, which may have missed more detailed morphological aspects of NV. We also did not distinguish between active and inactive NV. Regardless of activity, however, NV shape and the presence or lack of segmentation faults are more likely to be important for VRI identification.In conclusion, OCTA and different OCTA-based methods are important for the diagnosis of NVD, and the effectiveness of different detection methods may be related to different types of NVD.


Research on risk factors associated with bulimia nervosa symptoms (BN) in ethnic minorities has been limited. This study adds to the existing literature by providing the ethnicity- and gender-specific prevalence of BN in US inner-city youth and by exploring the longitudinal associations between a clinical level of BN and early risk factors assessed one year previously.The study was conducted on a representative sample of predominantly ethnic minority youth  = 12.77(1.29)); 60.0% African-American, 26.1% Hispanic American, 13.9% White). Self-reported information was obtained on BN and early risk factors . Multivariate analysis of covariance was used to examine the longitudinal associations.The 3-month BN prevalence was higher in girls (5.1%) than in boys (2.3%) (ratio 2.22:1). Significant differences in BN rates were found between White and African American students (higher in Whites), whereas Hispanic-Americans did not differ significantly from either group. Individuals with BN had significantly higher levels of early risk factors one year prior.Timely recognition of BN and associated early risk factors is important for early prevention and intervention strategies.The online version contains supplementary material available at 10.1186/s40337-021-00479-5. This longitudinal study evaluated the prevalence of bulimia nervosa (BN) symptoms in US inner-city predominantly ethnic minority youth and explored the associations between early risk factors and probable BN one year later. The study was conducted on a large group of inner city youth  = 12.77(1.29)); 60.0% African-American, 26.1% Hispanic American, 13.9% White). Self-reports were used to assess probable BN and early risk factors . The 3-month BN prevalence was higher in girls (5.1%) than in boys (2.3%). Significant differences in BN rates were found between White and African American students (higher in Whites), whereas Hispanic-Americans did not differ significantly from either group. Both boys and girls with BN had significantly higher levels of early risk factors as assessed one year previously. Timely recognition of BN symptoms and associated early risk factors is important for early prevention and intervention strategies.The online version contains supplementary material available at 10.1186/s40337-021-00479-5. Bulimia nervosa (BN) is a common eating disorder characterized by recurrent episodes of binge eating and compensatory behaviors such as self-induced vomiting to prevent weight gain , 81. ItsBN symptoms tend to peak in late adolescence , but in Although BN symptoms have been extensively explored in adolescents , 71, 77,Indeed, even though higher socio-economic status or White race are no longer considered as major risk factors for disordered eating e.g. , 40), as, as40]),Problems with mental health have long been considered among risk factors associated with BN, from both cross-sectional and longitudinal perspectives. Indeed, psychiatric comorbidity in eating disorders in adolescents is frequent (e.g. ), being Hence, there is a need to further investigate the prevalence of eating problems in large ethnically diverse adolescent populations, especially using a gender perspective, while also assessing potential risk factors, which could help to facilitate prevention efforts.The aims of this study therefore were to: (1) determine the gender- and ethnicity-specific prevalence of BN symptoms in a representative sample of inner-city ethnic minority youth, (2) explore whether adolescents with probable BN are more likely to have reported risk factors  a year earlier and whether these effects are moderated by gender and ethnicity. We will examine a range of mental health risk factors that have been theorized to increase the risk for BN in several previous studies. Considering that these problems are often comorbid and overlap, it is important to investigate how the multitude of these problems may be associated with BN symptoms over time in the same analysis, to explore whether individuals with possible BN differ from others in terms of early comorbid problems and whether these patterns may be to some extent gender- and ethnicity-specific.Based on previous research findings, we hypothesized that girls would report higher rates of BN symptoms than boys, but the gender ratio of BN may be lower than that reported in earlier studies. We did not make any specific hypothesis regarding BN rates in different ethnicities, given the substantial diversity of the results in previous reports. We further hypothesize that adolescents with BN will report higher levels of risk factors one year earlier and that these effects may be gender- and ethnicity-specific.p < .001) and more likely to be male (428 (59.9%) vs. 1310 (46.0%), χ2 = 4.09, p < .05). These drop-out students reported higher levels of depression (M (SD) = 5.22 (4.60) vs. 4.67 (4.19), t = 3.16, d = .150, p < .01) and posttraumatic stress (M (SD) = 22.96 (13.94) vs. 21.76 (13.07), t = 2.27, d = .089, p < .05). These findings suggest that attrition was selective across several key variables.The survey was administered to all eligible students in the New Haven (CT) public school system, including students in alternative programs and bilingual classes (17 public middle and high schools). In the spring of year 1, 3562 11–16 year old students completed the survey. This sample was followed until the next survey administration one year later. Eighty percent of the original sample (n = 2847) completed the survey in year 2. High attrition rates in longitudinal studies of urban ethnic minority adolescents are common , relateTo examine ethnicity as a variable in analyses, the sample was restricted to participants with an African-American, Hispanic-American, and White ethnic background, which resulted in the exclusion of 53 (1.9%) subjects from other ethnic groups .Finally, 168 adolescents had missing data. In relation to this, multiple imputation was undertaken  using the Markov Chain Monte Carlo (MCMC) method with a Predictive mean matching (PMM) model for continuous variables. No categorical background variables lacked data, as information on these variables was obtained from the school registry.The final sample  = 12.77(1.29))  was predominantly comprised of minority ethnicities , an accurate reflection of the local public school population . A majorParents were informed of the survey at the time of school registration, received a letter about the survey two weeks prior to its administration, and were offered the opportunity to decline participation. The passive informed consent procedure was approved by the university’s institutional review board and considered as an appropriate ethical procedure by the state legislature. Prior to survey administration, students were read a detailed assent form outlining their participation with the assurance of confidentiality, and were asked to sign it to indicate assent . Students completed the survey in a classroom setting during one class period during a regular school day. Trained administrators read all the questions aloud while students followed along with their copies of the survey, reading questions to themselves and circling responses in the booklet. A second administrator was available, providing help to individual students if requested. Surveys were administered in English and Spanish. All students in the respective grades attending school on the day of the survey’s administration were eligible to participate. Make-up administrations were performed at each school within one month of the initial administration for those who had been absent.This study is part of an ongoing project  that aims to assess risk and protective factors for adolescent adjustment, which has been administered annually in collaboration with the public school system in New Haven (CT) for nearly two decades. The survey has been extensively used in previous research and includes both scales available from the literature that have been used with similar populations and a few new scales developed specifically for this study, which have been subsequently validated against the existing scales in this particular study group .Depressive symptoms were assessed with an adaptation of the Center for Epidemiologic Studies-Depression Scale . Studie  and its  have exAnxiety symptoms were measured with a 12-item scale ).Similar to previous research with adolescents from the general population, ethnic minority economically disadvantaged youth from the present study reported a substantial number of BN symptoms. Adolescents with BN may already differ from others on a range of risk factors at a relatively early, preclinical stage, regardless of gender or ethnicity. Timely recognition of BN symptoms and associated early risk factors is important for early prevention and intervention strategies, which should be implemented regardless of background, ethnicity and gender. Future longitudinal research on large adolescent general population samples is needed in order to get a better understanding of the rates of BN and their dynamics over time by gender and in different ethnic groups.Additional file 1. Table S-1. Statistics for ANCOVA tests, conducted separately for each dependent variable (early risk factors) , η2, p).Additional file 2. Figures 1–5. Comparisons of the early risk factors scores by ethnicity and gender.


The differentiation between systemic inflammatory response syndrome and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy.We aimed to investigate the diagnostic value of Procalcitonin, Monocyte Chemoattractant Protein-1, soluble Mannose Receptor, Presepsin as early biomarkers of pediatric sepsis in comparison to systemic inflammatory response syndrome in severely ill children.This study included 58 children diagnosed as sepsis (group 1), 24 children with systemic inflammatory response syndrome without infection (group 2), and 50 healthy children as controls (group 3). All the plasma levels of the studied biomarkers were measured and ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS.The area under the curve for Monocyte Chemoattractant Protein-1 was 0.926 (0.846-0.927) with sensitivity 100% and specificity 62.5%. The soluble Mannose Receptor had the highest sensitivity (100%), with AUC equals 1(.0.956-1.0) and specificity of 100%. The cut-off values for Procalcitonin, Presepsin, soluble Mannose Receptor, and Monocyte Chemoattractant Protein-1 and were: 0.62 ng/ml, 100 pg/ml, 13 ng/ml and 90 pg/ml, respectively. In septic cases, both soluble Mannose Receptor and Procalcitonin have positive correlations with the severity of sepsis, low Glasgow Coma Scale, ventilatory support, use of inotropic drugs and mortality rate  for soluble Mannose Receptor and  for Procalcitonin.Soluble Mannose Receptor, Presepsin, and Monocyte Chemoattractant Protein-1 can be used to differentiate between sepsis and SIRS in critically ill children. Procalcitonin, Monocyte Chemoattractant Protein-1 (MCP-1), soluble Mannose Receptor (sMR) and Presepsin are known to be useful biomarkers in the diagnosis of sepsis.We used these markers to investigate their diagnostic significance in severely ill children admitted with signs of acute and severe inflammation and correlate these markers to the severity of sepsis.We also assess whether these biomarkers are useful to discriminate sepsis from SIRS in critically ill children with suspected infection.The recent Sepsis-3 consensus definition emphasized that sepsis is differentiated from uncomplicated infection by the presence of life-threatening organ dysfunction as a result of a dysregulated host response to infection .Systemic inflammatory response syndrome (SIRS) is defined as an inflammatory condition involving the entire body. That is the reaction of the body to an insult that is either contagious or non-contagious such as burns, autoimmune disorders, pancreatitis, trauma, and other conditions .Sepsis is difficult to be distinguished from other non-infectious situations in critically ill patients presented with clinical signs of severe inflammation. This topic has a vital importance as the management differs greatly in these two different conditions. Thus, there is an unfulfilled requirement for clinical or laboratory diagnostic tools to distinguish between SIRS and various forms of sepsis .Differentiation between SIRS and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy .As SIRS is diagnosed clinically while sepsis is further diagnosed by the presence or suspected infection, it is essential to develop useful biomarkers to confirm or eliminate the suspected infection, stage of sepsis, make a therapeutic decision, as well as monitor response to treatment .Procalcitonin (PCT), a precursor for calcitonin, is produced by all body tissues . It has Monocyte Chemoattractant Protein-1 (MCP-1) is a strong chemoattractant of mononuclear cells and a regulatory mediator in sepsis. MCP-1 has an essential immunomodulatory function to maintain the balance between pro-inflammatory and anti-inflammatory cytokines in sepsis. Elevated concentrations of MCP-1 were reported in adult patients with sepsis and septic shock .The soluble Mannose Receptor (sMR) is expressed primarily by subsets of macrophages, dendritic and endothelial cells. The sMR is shed from the cell surface due to inflammation, and the receptor can be detected in the blood . It is aPresepsin, (sCD14-subtypes) was found to have a value in the diagnosis of sepsis. CD14 can generate a strong and exaggerated systemic inflammatory reaction and activate the fibrinolytic and coagulation systems, leading to SIRS, disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome (MODS), and septic shock .CD14 can also turn on a sequence of inflammatory and signal transduction pathways that result in the systemic inflammatory response [The aim of our study is to investigate the diagnostic significance of PCT, MCP-1, sMR, and Presepsin in severely ill children admitted with signs of acute and severe inflammation and correlate these markers to the severity of sepsis. We also assess whether these biomarkers are useful to discriminate sepsis from SIRS in critically ill newly hospital admitted children with suspected infection.This is a hospital-based prospective case control comparative study conducted at the Pediatric Intensive Care Unit (PICU) at Minia University Children Hospital during the period from April 2019 to November 2019. Our study included eighty-two children admitted to our PICU with signs of acute and severe inflammation (group 1 and 2) and fifty apparently healthy children as controls. According to the the 2005 Consensus definition for paediatric sepsis , we clasGroup (1) included 58 children diagnosed as sepsis or septic shock.Group (2) included 24 children diagnosed as SIRS without infection.Group (3) included 50 healthy children served as controls.Core temperature of > 38.5 °C or < 36 °C.Tachycardia, defined as a mean heart rate > 2 SD above normal for age in the absence of external stimulus, chronic drugs, or painful stimuli; or otherwise unexplained persistent elevation over a 0.5- to 4-h time period OR for children < 1 yr old: bradycardia, defined as a mean heart rate < 10th percentile for age in the absence of external vagal stimulus, β-blocker drugs, or congenital heart disease; or otherwise unexplained persistent depression over a 0.5-h time period.Mean respiratory rate > 2 SD above normal for age or mechanical ventilation for an acute process not related to underlying neuromuscular disease or the receipt of general anesthesia.Leukocyte count elevated or depressed for age (not secondary to chemotherapy-induced leukopenia) or > 10% immature neutrophils.The presence of at least two of the following four criteria, one of which must be abnormal temperature or leukocyte count:A suspected or proven  infection caused by any pathogen OR a clinical syndrome associated with a high probability of infection. Evidence of infection includes positive findings on clinical exam, imaging, or laboratory tests .SIRS in the presence of or as a result of suspected or proven infection.Sepsis plus one of the following: cardiovascular organ dysfunction OR acute respiratory distress syndrome OR two or more other organ dysfunctions.Sepsis and cardiovascular organ dysfunction .Immediately after PICU admission, all patients with suspected sepsis were included in our study. We excluded cases whose parents refused to participate, Patients who died within the first eight hours after admission, discharge within the first 24 h after admission. Children with underlying malignancies, chronic disease or immunosuppression state were also excluded from our study.Studied children were subjected to thorough history taking; gender, age and cause of admission stressing on the focus of infection. General examination and vital signs monitoring  were done for all patients .A standard Pediatric Risk of Mortality score (PRISM III-24) was done during the first 24 h after admission for each septic patient to determine the severity of sepsis .Both primary outcome measures  and secondary outcome measures  were also recorded.Within 12 h after admission, under complete aseptic conditions, three ml blood samples were drawn from all cases for Complete Blood Count (CBC), C- reactive protein (CRP), renal, liver functions and the studied biomarkers. Plasma was collected by centrifugation at 4 °C, aliquoted, and stored at − 70 °C till assay.Cell Dyne 3500 automated cell counter was used for complete blood count of blood collected in EDTA-containing tubes. Renal and hepatic functions; including creatinine level, direct and total bilirubin, and alanine aminotransferase (ALT) were assessed in all patients by BM Hitachi 911 Chemistry Analyzer. PCT and MCP-1 were detected in serum by bioMérieux SA kit  and BioSource immunoassay kit , respectively. Measurement of plasma concentrations of Presepsin was performed by PATHFAST immunoassay analytical system . The sMR was detected by enzyme linked immunosorbent assay .Reference ranges: sMR = 1-256 ng/mL, Procalcitonin = 0.15 ng/mLPresepsin = 320 pg/ml, MCP-1 = 1-800 pg/ml.Before initiation of antibiotics and within the first 12 h after admission, two ml of blood collected by sterile venipuncture for blood cultures. Blood cultures were done by the Bact/Alert FA .Bacteremia was identified when blood culture had microbial growth. Positive samples were then subcultured on blood agar, MacConkey agar, and chocolate agar media. Isolated organisms were differentiated by colony morphology and Gram-staining. Identification of Gram-positive and Gram-negative bacteria was performed by the conventional biochemical reactions.Positive blood cultures confirmed the diagnosis of bacterial sepsis. Other investigations as chest X-ray, urine cultures or deep tissue swabs were performed when needed.The collected data were coded, tabulated, and statistically analyzed using SPSS program  software version 25.Descriptive statistics were done for parametric  quantitative data by mean, Standard deviation (SD) and minimum and maximum of range and for non-parametric quantitative data by median and interquartile range (IQR), while for qualitative data by frequency and percentage.Distribution of the data was done by Kolmogorov Smirnov test and Shapiro Wilk test.Analyses were done between the three groups for parametric quantitative data using One way ANOVA test between the three groups followed by post hoc Tukey’s analysis between each two groups and for non-parametric quantitative data using Kruskal Wallis test between the three groups followed by Mann Whitney test between each two groups.Analyses were done between the two groups for Qualitative data using Chi square test.Correlation was done using Pearson’s correlation coefficients.ROC curve analysis was used to determine AUC, Sensitivity, Specificity, PPV, NPV and accuracy of variables predicting sepsis.P value ≤0.05).The level of significance was taken at : 58 children diagnosed as having sepsis or septic shock.Group (2): 24 children diagnosed as having SIRS without infection.Group (3): 50 apparently healthy children as controls.One hundred thirty-two children were included in our study. Children were classified into three groups:Demographic and clinical data are presented in Table p < 0.05)  Table .Table 2LSepsis secondary to pneumonia was detected in 21 cases (36.2%). 25 children (43.1%) presented with gastroenteritis. Central Nervous System (CNS) infection was detected in 12 cases (20.7%), while cases with SIRS were secondary to either trauma or hemorrhage.Klebsiella pneumoniae, 14 cases (24.1%) had Staphylococcus aureus: 12 cases (20.68%) had Escherichia coli, 10 cases (17.24%) had Coagulase negative staphylococcus (CONS) and 6 cases (10.3%) were Candida albicans. Blood cultures were negative for all SIRS cases.Positive blood cultures were obtained in all sepsis cases. The following bacteria were isolated from the blood cultures: 16 cases (27.58%) had p < 0.001)  Fig. .Fig. 1a:ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS. Area under the ROC curve (AUC) of MCP-1 was 0.926 0.846-0.972) with sensitivity 100% and specificity 62.5% The AUC for PCT was 0.966 (0.9-0.993) with 100% sensitivity and 83.33% specificity. As regards Pesepsin; the AUC was 0.751 (0.643-0.840) with a sensitivity of 67.24% %, a specificity of 83.33%. The sMR had the highest sensitivity (100%), with AUC equals 1(0.956-1) and specificity of 100%  and between MCP-1 and sMR   Table .Table 5Cp = 0.019) , low GCS, ventilatory support, use of inotropic drugs and mortality rate  for sMR and  for PCT. While MCP-1 was only positively correlated with PRISM  with high sensitivity and fair specificity at a cut-off point of 0.62 ng/ml. Many researchers have studied the diagnostic and prognostic exactness of PCT measurement .Recent studies have shown that PCT is not as a good predictor of sepsis as newly examined biomarkers in adult and pediatric sepsis and septic shock , 27.Presepsin was recognized as a novel biomarker for sepsis in many studies, most of them were performed on neonates with sepsis , 29. ShoYoon et al. stated that Presepsin has higher both sensitivity and diagnostic accuracy, but lower specificity than PCT or CRP in detecting sepsis in children (AUC of presepsin was 0.925 with sensitivity 0.94 and specificity 0.71) .Bellos et al. concluded that the use of Presepsin in the early neonatal period in high-risk populations as its diagnostic accuracy seems to be high in detecting neonatal sepsis (AUC of presepsin was 0.9751 with sensitivity 0.91 and specificity 0.91) .Other studies have found that the plasma levels of Presepsin in infected patients were higher than that in non-infected patients .In our study, Presepsin was higher in children with sepsis. This coincides with Contenti et al. who studied the concentration of Presepsin in emergency patients on admission .This study has many limitations and strengths. First, strengths include blind investigation of cases by clinicians without awareness of the level of the biomarkers. Also, contrary to other studies , 35. OnlWhile limitations include that our patients’ number was not very high. Another limitation is that our findings may not be applicable to patients with mild illness or localized infections that do not require ICU admission as in these cases, the levels of the biomarkers may be below the submitted cutoff values.Although our study included a relatively small number of patients, it suggests a potential role for sMR, Presepsin, and MCP-1 as biomarkers in differentiating between sepsis and SIRS in critically ill children, so more studies should be done on a larger number of children. Furthermore, our results confirmed the former reports that PCT is one of the most useful sepsis biomarkers in critically ill children. These findings could direct clinicians in their practical decision-making and complex management of severely ill children who need much interference in short time.Biomarkers as sMR, Presepsin, and MCP-1 can be used to differentiate between sepsis and SIRS in critically ill children. That may help in taking urgent treatment decisions.


Fusobacterium necrophorum. LS is usually suspected in fit young adults with prolonged or prior pharyngeal infection. Atypical Lemierre's syndrome is commonly defined as Fusobacterium-associated thrombophlebitis outside the head-neck veins and usually occurs in older patients than typical Lemierre's syndrome. Here we present a case of atypical LS in a septuagenarian healthy Caucasian male with no prior history of pharyngitis and in whom both computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated partial portal vein thrombosis associated with Fusobacterium nucleatum. This case report confirms previous reports of Fusobacterium nucleatum-associated LS variants presenting with abdominal vein thrombosis and illustrates clinical recovery after a combination of anticoagulation and antibiotic therapy.Lemierre's syndrome (LS) is characterized by thrombophlebitis of the internal jugular vein caused primarily by  B. fragilis, E. coli, and Streptococcus spp., among others [Septic thrombophlebitis is the occurrence of venous thrombosis associated with bacteremia , which cg others , 6.Fusobacterium sepsis, more commonly associated with thrombophlebitis of the internal jugular vein, also known as Lemierre's syndrome, is a rare cause of pylephlebitis or other forms of thrombophlebitis outside of the head-neck syndrome, especially in the gastrointestinal system. These conditions are sometimes referred to as atypical Lemierre's syndrome [Fusobacterium-associated thrombophlebitis of the portal vein in an otherwise healthy Caucasian male.syndrome , 8. In tA 73-year-old Caucasian man with a past medical history of hypertension, hyperlipidemia, and melanoma presented to the Emergency Department (ED) with several weeks of fever. He had visited Arizona with his family prior to the onset of symptoms. On his return, he had developed a non-productive cough, fever, cold sweats, and weight loss which prompted him to visit his primary care physician. He was treated with supportive care and had an outpatient chest/abdomen/pelvis non-contrast CT scan done which showed a hazy density in the mesentery and an increase in the number of small lymph nodes. The CT scan also showed prominent small bowel folds involving the jejunum and an 8 mm ground glass nodule in the right lung. He was seen in the ED the next day and was discharged with ciprofloxacin for pyuria. Coccidioidomycosis antibodies were found negative during this visit. He was referred to an Infectious Disease (ID) specialist and was prescribed fluconazole for empiric treatment of Valley Fever (coccidioidomycosis).2 was 98% on room air. He was alert and oriented to person, place, time, and situation with all cranial nerves intact. Physical exam showed no lymphadenopathy and was otherwise unremarkable.Due to persistent fever and failure to respond to empiric therapy of Valley Fever, the patient presented to the ED 12 days later where he was admitted to the hospital. His blood pressure (BP) was 125/61 mmHg, pulse was 108 bpm, oral temperature was 101.5°F (38.6°C), RR was 20 bpm, and SpO∗ 109 cells/L), elevated neutrophils (85.1%), low red blood cell count (3.71 million cells/mm3), hemoglobin (10.4 g/dL), low hematocrit (31.4%), and low lymphocytes (5.5%). Basic metabolic panel showed hyponatremia (130 mEq/L), hypokalemia (3.2 mEq/L), hypocalcemia (7.6 mg/dL), and low chloride (91 mEq/L). Liver function tests showed abnormal proteins (2+), low albumin (2.3 g/dL), and elevated alkaline phosphatase (163 U/L). Other blood work showed elevated lactate (2.3 mmol/L), erythrocyte sedimentation rate (92 mm/hr), and C-reactive protein (>300.0 mg/L). All other parameters for blood were unremarkable. Urinalysis was significant for protein (1+), bacteria (2+), white blood cells (6–10), and red blood cells (5–10). All other parameters were within normal limits. Urine bacterial culture and Legionella antigen were both negative.A review of complete blood count (CBC) on admission showed significant elevated white blood cell count  with possible thrombosis in the SMV as well. New diffuse moderate abdominal ascites was also noted. Abdominal ultrasound was significant for multiple echogenic liver lesions that warranted further evaluation via MRI. MRI with contrast of the abdomen confirmed portal vein thrombosis and intraperitoneal fluid. It also confirmed the presence of multiple hepatic lesions suggestive of possible hepatic abscesses given the patient's fever and leukocytosis. Blood smear was negative for plasmodium. A purified protein derivative (PPD) skin test for tuberculosis was negative. Stool cultures were negative for While admitted to the hospital, the patient was started on anticoagulation with Lovenox (enoxaparin) 1 mg/kg every 12 hours as well as the antibiotics Zosyn (piperacillin/tazobactam), 3.375 g q6 hrs totaling 13.5 g (12 g piperacillin/tazobactam) and Flagyl (metronidazole). Metronidazole was later switched to doxycycline. Once stool cultures results returned negative, doxycycline was stopped. On discharge from the hospital, he was prescribed a daily dose of warfarin 5 mg anticoagulation and bridging with enoxaparin. Enoxaparin was discontinued when the INR reached therapeutic doses. He was also treated with ertapenem 1 g daily for 6 weeks at the infusion center. He was told to stop his other medications: lovastatin 40 mg and Dyazide (triamterene-hydrochlorothiazide (HCTZ)) 37.5–25 mg.In the weeks following discharge, the patient developed massive ascites and bilateral pitting edema of the legs. He was immediately referred to a hepatologist and was treated with diuretic therapy. The patient completed treatment and eventually made a full recovery in the subsequent months.Fusobacterium necrophorum, a Gram-negative bacillus. Pathogens colonize the area and then drain into the lateral pharyngeal space, where they approach the internal jugular vein [F. necrophorum's ability to aggregate platelets contributes to the formation of a thrombus within the tonsillar veins [A typical case of Lemierre's syndrome is initiated by a pharyngeal infection caused by lar vein  The firsar veins . This abar veins .Fusobacterial superinfection. In addition to a suggestive past medical history, patients at increased risk of developing Lemierre's syndrome are adolescents or young adults who were previously fit. Lemierre's syndrome is a specific form of septic thrombophlebitis, which includes venous thrombosis associated with local bacterial infection occurring at several anatomic locations [Fusobacterium involved in the portal vein thrombosis differs from that of a typical case of Lemierre's syndrome. Typically, Fusobacterium necrophorum is involved, but in the atypical cases, the responsible pathogen points to Fusobacterium nucleatum [Fusobacterium necrophorum infection [Fusobacterium spp. infection.A mucosa already damaged by an infection may create an environment conducive for a ocations . Currentocations , 12. Thenfection , atypicaWhether Lemierre's syndrome presents typically or atypically, all reported cases had fever and leukocytosis . In an aFusobacterium infection, i.e., F. nucleatum remains the main cause of infection and thrombosis in portal veins of elderly population. Evidence from a case report dating back to 2014 mentioned two cases involving portal vein thrombosis in context of Fusobacterium infections. The report mentioned that while Fusobacterium is known to induce platelet aggregation, thrombotic events outside of the head and neck are rare [This case report strengthens the existing literature related to variants of Lemierre's syndrome. It contributes to the main differences seen in cases of portal vein thrombosis secondary to are rare , 14. Wheare rare , 14.F. nucleatum bacteremia [F. nucleatum-induced pylephlebitis. Further investigations should emphasize on cases about Fusobacterial infections of the portal vein in previously fit individuals of an older age.In our case, the patient was an older male outside the typically younger age range of Lemierre's syndrome, and he had no prior infection of the head-neck area. To our knowledge, there are only six other reports of pylephlebitis associated with cteremia , of whiccteremia . No infoFusobacteria species: Fusobacterium nucleatum. Pre-existing conditions or environmental factors are inconclusive in determining the reasons why a patient would develop an atypical case of Lemierre's syndrome, and further indications from current literature are insufficient to show evidence that supports a solid reasoning, as there are so few cases of F. nucleatum-induced pylephlebitis. However, regardless of its presentation, Lemierre's syndrome leads to widespread thrombosis and sepsis affecting many organ systems, and, to prevent these complications from developing, it needs to be identified rapidly and treated accordingly.In summary, it is important for current literature to consider a variant of Lemierre's syndrome which causes pylephlebitis in its initial stages of infection, resulting from the colonization of the portal vein by a bacterium, that also belongs to the


Except for oxygen pulse, these significant changes could also be observed at the anaerobic threshold. Maximal heart rate and pulmonary function parameters remained essentially unchanged. Conclusion: Regular recreational skiing improves cardio-pulmonary fitness along with breathing economy and thus can contribute to a heart-healthy lifestyle for the elderly.Objectives: To investigate whether recreational alpine skiing in the elderly can improve cardio-pulmonary fitness. Design: Randomized controlled study with pre–post repeated measurements. Methods: A total of 48 elderly participants (60–76 years) were randomly assigned to either participate in a 12-week guided recreational skiing program  or to continue a sedentary ski-free lifestyle . Cardio-pulmonary exercise testing (CPET) and pulmonary function testing were performed in both groups before (PRE) and after (POST) the intervention/control period to compare parameters PRE vs. POST CPET. Results: At baseline, IG and CG did not differ significantly with respect to CPET and pulmonary function parameters. At POST, several measures of maximal exercise capacity and breathing economy were significantly improved in IG as compared to CG: maximal oxygen capacity (IG: 33.8 ± 7.9; CG: 28.7 ± 5.9 mL/min/kg;  Cardio-pulmonary exercise testing (CPET) is used in medicine in general and in sports medicine as well as sports and exercise science in particular to assess and monitor cardio-pulmonary fitness and training in healthy subjects as well as in patients ,2.2max) is a frequently measured variable in clinical practice to quantify cardio-pulmonary exercise capacity and is often used as the primary outcome parameter in CPET and/or exercise training studies [2max as a single parameter used in the assessment of the cardiovascular risk/benefit profile of the participants in the SASES-study [Maximal oxygen capacity  and forced expiratory volume per second (FEV1) with subsequent calculation of the Tiffeneau index (ratio of FEV1 to FVC) and peak expiratory flow (PEF). A meta-analysis in young participants and athletes undergoing specific respiratory muscle training showed a significant effect on physical performance independent from pulmonary function parameters, where no changes were found, indicating a predominance of adaptative mechanisms in the gas exchange system . DeterioThe aim of this study was to collect data from CPET and pulmonary function testing before and after a guided alpine skiing program in order to assess whether, and if so, through which mechanisms, cardio-pulmonary changes could be achieved at rest and during maximal exercise.n = 29; age: 66.6 ± 2.1 years, 45% female) or a control group . The IG performed guided skiing for 12 weeks—a common time frame for a winter season in the alpine region—averaging 28.5 ± 2.6 total days and 3.5 h of skiing per day. A detailed analysis of the composition of an average skiing day in rest, lifting time, and actual skiing is provided elsewhere [https://clinicaltrials.gov/show/NCT01248910).The design of this study has been previously reported elsewhere . Brieflylsewhere . The CG lsewhere . The stuBefore (PRE) and after (POST) the intervention/control period, we performed CPET and pulmonary function testing in both groups. First, we performed pulmonary function testing in resting condition. Data were collected using the EasyOne Spirometer . We determined FVC, FEV1, and PEF, and thereby calculated FEV1/FVC. Data collection in pulmonary function testing met the standard criteria for spirometry execution according to scientific standards to detect pathological patterns .Thereafter, we measured common CPET parameters during an incremental ramp-protocol starting at 50 Watt (W), increasing 10 W every minute until individual physical exertion was reached. Averaged results at (a) rest, (b) the estimated anaerobic threshold , and (cT). By using gas-exchange monitoring, oxygen consumption and produced carbon dioxide (VO2 and VCO2) were assessed; thus, oxygen pulse  [2/VO2 [CPET variables comprised power in W, heart rate (HR), respiratory rate (RR), total ventilated air (VE), and tidal volume (Ve volume ) as wellectively ) were caumption) ) and res) [2/VO2 ).max , plateau in VO2max despite increasing work load, or RER reaching/exceeding 1.1. A pathological CPET was defined as VO2 at AT < 11 mL/min/kg or maximal VE/VCO2-slope > 34, being a risk factor for early cardiovascular death, as defined by Gitt et al. [Exertion criteria were defined as previously suggested by Balady et al. : reachint et al. .p < 0.05. The Shapiro–Wilk test was used to check for normal distribution in small sample groups. If data were normally distributed, intra-group comparisons were made using paired t-tests, whereas inter-group comparisons were performed by unpaired t-tests. If data were not normally distributed, we employed the Mann–Whitney U or Wilcoxon signed-rank tests. We used GraphPad InStat  and SPSS .Descriptive statistics are presented as means ± standard deviations. Statistical significance was set at n = 39; IG = 22, CG = 17) are reported in p = 0.008). All participants had a normal age-related cardio-pulmonary fitness and pulmonary function. No pathological patterns in CPET were found. In IG, two out of the 29 participants did not undergo CPET testing due to claustrophobia while wearing the mask. A total of eight participants (IG: 5 CG: 3) had to be excluded from the study because maximal exertion criteria were not reached, resulting in a total number of 22 participants with complete measurements in IG and 17 in CG. Baseline characteristics of the study population . Maximal heart rate did not change ; also, heart rate at AT was not significantly different between the two groups .An overview of CPET measurements is provided in 2max was found to be significantly higher in the IG (2588 ± 651 mL/min) as compared to CG (2093 ± 585 mL/min) corresponding to a difference of 19.0% (p = 0.021). In addition, relative VO2max adjusted to body weight differed significantly at POST  and at AT . Consequently, MET also increased . Absolute VCO2max at POST was higher in IG as compared to CG , also after adjustment for body weight . This effect was also seen at AT .At POST, absolute VO2 pulse at rest (IG vs. CG: p = 0.341). However, IG participants showed significantly higher O2 pulses at maximal exertion  and AT .At POST, we report no difference between groups in Op = 0.025). This increase was mainly driven by a more economic ventilation with a significant increase in maximal VT in IG , whereas RR did not change in IG (p = 0.805). No changes of VE, VT, and RR at resting state were observed.We observed a significant difference in VE at maximal exertion at POST . For EqCO2, no changes could be observed at maximal exertion (p = 0.616) or AT (p = 0.631) but was found higher by trend at resting .EqOEssentially no changes were observed in pulmonary function measurements throughout the study, as shown in In this study, we demonstrate that guided alpine skiing two to three times per week over the course of 12 weeks in otherwise sedentary elderly participants induced significant changes in the cardio-pulmonary system as assessed by CPET but not in pulmonary function. Most importantly, changes in aerobic capacity, oxygen pulse, and maximal minute ventilation resulting in a better performance during exercise were observed.2max to be the most predictive parameter for exercise capacity [2max, as we report here, is a well-established finding in exercise training studies. We herewith conclude that alpine skiing can induce a clinical and statistically significant increase in exercise capacity.Similar results from more traditional exercise training studies with elderly participants have been previously observed; most of them reported VOcapacity ,19. Acco2max increased in IG from PRE to POST (+12%), and there was also a significant difference compared to CG (Δ 15%). Seals et al. and Hagberg et al. [2max after a comparable amount of exercise training . Badenhop et al. showed that there were no significant differences between low- and high-intensity training groups after 9 weeks of treadmill training of >60-year-old participants [2max, 20–30 min of moderate-intensity walking at least three times per week) and 6 months with high-intensity supervised training . This intervention group was compared to a sedentary control group. Seals et al. showed that low-intensity unsupervised training resulted in a significant improvement of VO2max; however, supervised high-intensity training resulted in an additional and even greater increase in VO2max [2max with previous literature on low-, moderate-, and high-intensity exercise training on elderly participants, alpine skiing induced changes best compared to moderate to high-intensity rather than low-intensity exercise training.Both relative and absolute VOg et al. ,21 descr2max shows a natural decline while aging [2max (+38% in elderly vs. 29% in young) but also a maximal estimated cardiac output (+30% vs. +14%) and stroke volume (+21% vs. +9%) compared to baseline. Since a higher VO2max along with a raised O2 pulse  in eldeividuals , we conc2 in IG was not only significantly higher at maximal exertion but also at AT, which implies relevant metabolic adaptation already at an earlier stage of exertion. This is in keeping with our previous findings of muscle biopsies in IG, where significant alterations in both structure and metabolism of the musculature [2 and VCO2 at maximal exertion and AT. VCO2 at AT and at maximal exertion were higher in IG compared to CG, respectively. We interpret this finding as an adaption toward a more efficient metabolism, indicating a similar capability of the body to dispose acidotic equivalents.As a consequence of the alpine skiing training regimen, VOculature ,25 were max is limited by age, gender, and genetics with only low interference of fitness effects [2-mediated increase in oxygen content inside every ejected stroke, surrogated by the O2 pulse, which was 22% higher in IG than CG.The increased oxygen demand in the musculature during exercise is predominantly supplied by an increase in cardiac output. As HR effects , neithermax and at AT is connected to a significantly greater VT, as seen in IG from PRE to POST. Given the similar baseline parameters in IG and CG, a larger tidal volume, triggered by a higher exercise demand, suggests a better ventilatory efficiency and has greater effect on gas exchange than an increased respiratory rate [2-driven cellular oxygen supply.Increased VEory rate . It is a2 (VE/VCO2) has been observed to be a strong predictor for cardiovascular death [2, VO2, and VE, but since these changes were positively correlating with each other, no changes in EqCO2 or EqO2 could be observed.Furthermore, especially, the identification of the lowest EqCOar death . We repoGood fitness levels correspond to a general health benefit preventing cardiovascular  and manyData on pre–post exercise training on pulmonary function parameters are scarce ,13. In aIntermittent hypoxia is a natural effect of alpine skiing using skiing lifts as the uphill transportation mode. The subjects take, e.g., a cable car to be transported uphill and then ride downhill in a repetitive fashion. As the participants of our study were tracked using GPS sensors, the average altitude covered per skiing day could be calculated. Müller et al. report an average of 4885 ± 816 vertical downhill meters per skiing day that comprised of 9.3 ± 3.0 downhill runs per skiing day . As the n = 8) or due to claustrophobia while wearing the CPET mask (n = 2). However, these are aspects that are known as real-world problems in CPET. Finally, our study did not account for the long-term sustainability of our findings. Furthermore, our study is limited due to a relatively small sample size. However, due to the huge effort to facilitate a guided skiing intervention for 12 weeks for 2 to 3 days per week and the significant changes we herewith report, we think that our sample size is reasonable to draw meaningful and clinically relevant conclusions and that a larger sample size would result in similar results. Up until now, to the best of our knowledge, this is the only randomized controlled study on supervised recreational alpine skiing in the elderly; however, we certainly look forward to further research on this topic with more included subjects to further deepen our understanding of the beneficial effects of alpine skiing in the elderly.To the best of our knowledge, this is the first randomized study to comprehensively investigate CPET and pulmonary function data in a pre–post repeated measurement design in recreational skiers of advanced age. Rossi et al. have previously discussed all studies on recreational alpine skiing, including SASES . HoweverIn conclusion, we demonstrate that a season, i.e., 12 weeks, with two to three recreational days of skiing per week performed by elderly skiers has a positive impact on the cardio-pulmonary fitness, in part due to improved breathing economy, and can thereby contribute to a heart-healthy lifestyle.In the elderly, regular recreational alpine skiing has similar effects on physical fitness as has been previously reported in moderate-to-high endurance training programs.While breathing economy, oxygen pulse, and oxygen consumption during exercise were significantly improved after alpine skiing, pulmonary function remained essentially unchanged.Downhill skiing is a potent and attractive exercise modality to improve cardio-pulmonary fitness in the elderly in alpine regions.Practical implications follow:


Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) are commonly used drug-delivering devices for patients with chronic airway diseases. Appropriate peak inhalation flow rate (PIFR) and inhaler technique is essential for effective therapy. We aimed at optimizing inhalation therapy through the analysis of PIFRs in patients with chronic obstructive pulmonary disease (COPD) or asthma as well as the effect of technique training using In-Check DIAL® to help patients to achieve their optimal inspiratory flow rates.The study continuously enrolled patients who were diagnosed as COPD or asthma from respiratory clinics. PIFRs were described and analyzed between the newly-diagnosed and follow-up patients, and the stable and acute exacerbation patients, respectively. Every participant was trained inhaler technique using In-Check DIAL®. PIFRs before and after training was compared by self-control analysis.p < 0.001) for most patients, but no significant variation was found in patients with acute exacerbation (p = 0.822).Among a total of 209 patients, the average age was 56.9 years. For DPIs users, 10.8% patients had a PIFR < 30 L/min and 44.1% patients had a PIFR ≥ 60 L/min before technique training. After technique training, scarcely patient (1.5%) had a PIFR < 30 L/min, and 60.5% patients had a PIFR ≥ 60 L/min. The patient’s average PIFR increased by 5.6L/min after training. The increase in PIFR before and after training was significant  and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142). Chronic respiratory diseases, especially Chronic obstructive pulmonary disease (COPD) and asthma, are common diseases worldwide with leading mortality and morbidity. In China, the prevalence of COPD in patients over 40 years old was 8.2–13.7% , 6.Inhalation therapies, including inhaled corticosteroid (ICS), long-acting β2 agonists (LABA) and long-acting muscarinic antagonists (LAMA), play an important role for the treatment and management of both COPD and asthma . InhalerRecently, PIFR has been believed as a measure to assess patients' capacity to use DPIs . DPIs apAppropriate technique for the usage of inhalers is quite important for the efficacy of inhalation therapy that improper technique is significantly associated with uncontrolled symptoms and increased exacerbation rate . For patIn the current study, we aimed to investigate the PIFRs of patients with COPD or asthma, factors that affect PIFRs and the effect of inhaler technique training on optimizing patients’ PIFRs before inhalation therapy. Through this study, the optimized inhalation therapy based on PIFR should be guided both in selection of the most acceptable inhaler for patients and in training to improve inhaler technique.We conducted a prospective, self-control, single-center study at Respiratory Clinic in Zhongshan Hospital of Fudan University, Shanghai, China. All participants have signed an informed consent before being recruited. The study has registered in chictr.org.cn (ChiCTR1900024707) and been approved by the Ethics Committee of Zhongshan Hospital of Fudan University (B2019-142).Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease(GOLD) 2019 Report ) and symptoms . Although training has improved the patients’ inhaler technique of pMDI to some extent, but it was not statistically significant . It is worth noting that there were still 7.5% subjects using pMDIs with a PIFR greater than 90L/min after training.In our study, 13(16.3%) of the patients who used pMDIs (N = 80) had a PIFR greater than 90 L/min before training, among them 7 (46.2%) were COPD patients and 6 (53.8%) were asthmatic patients. Most of them 12 (92.3%) had stable diseases. Compared with subjects with PIFR less than 90L/min, they had similar lung function , FEV1%, FEV1/FVC, RV/TLC and CAT score, but was weakly relative to FEV1, PEF, IC, and mMRC score. Among them, PIFR0 was positively correlated with FEV1, PEF, and IC . On the contrary, PIFR0 showed a negative correlation with mMRC score .As shown in Table 1% < 30%) is relatively small  since the patients we enrolled were all outpatients. Though after training, 39.5% of patients were not yet able to achieve the optimal PIFR (60L/min), which showed that there were still quite a few patients with a suboptimal inspiratory flow rate even in patients with mild, moderate or severe COPD (GOLD I–III).Different inhalers have different requirements for the patient's inspiratory flow rate and technique . AlthougIn this study, in addition to routine instructional video and oral guidance by physicians, we additionally emphasized the application of In-Check DIAL® in technique training. Our study has shown that 10.8% of patients using DPI could not achieve the minimum PIFR (30L/min) and 55.9% of patients could not achieve the optimal PIFR (60L/min) before technical training. After training, almost no patients had a PIFR less than 30L/min, and the number of patients who did not reach the optimal flow rate was significantly reduced, which revealed that technique training helped to significantly increased both the value of PIFR and the proportion of patients that reached the minimum and optimal flow rate. Our attempt to train patients with In-Check DIAL® truly contributed to improving PIFR of patients with COPD or asthma. Moreover, the improvement of PIFR in COPD patients before and after training was more significant than that of asthmatic patients. Therefore, we considered that COPD patients need more training, probably because asthma patients were younger and stronger in learning ability than COPD patients.0, PIFRAT and PIFRBT) in new-diagnosed (indicating no effective treatment had ever be used) vs. follow-up patients and patients in exacerbation vs. stable stage, we found that PIFR of ND/FU group or AE/Stable group showed a significant difference. It meant that compared with follow-up patients, newly-diagnosed patients who were given inhalation therapy for the first time benefited more from inhaler technique training in improving the ability of using DPIs; and compared with AE patients, patients in the stable phase benefited more in improving PIFR.We have investigated the distribution of PIFRs in patients with different clinical conditions in this study. By comparing PIFR  and the smallest proportion of PIFRBT greater than or equal to 60 L/min (26.4%), but FU group had the largest proportion of PIFRBT greater than or equal to 60 L/min (54.5%). These data suggest that newly diagnosed patients should strengthen knowledge education and inhaler technique training, and pMDIs may be prescribed for some patients with suboptimal PIFR (DPIs can be prescribed after improvement).From the distribution of PIFRAT greater than or equal to 60 L/min (41.2%), which is significantly lower than that of the stable group (68.3%). In the AE group, the improvement in PIFR before and after training (P > 0.050) did not reach statistical significance, indicating that many AE patients had poor inhalation ability and the benefits of training for AE patients were limited. It can be found that when the influence of technical factors on PIFR is excluded, AE patients had a higher suboptimal rate and a worse ability to use DPIs than stable patients, but physicians kept giving DPIs to them (AE patients used 1.00 DPIs per capita). Previous researches have shown similar conclusions that acute exacerbations were associated with decrease in PIFR [Among all the groups after teaching, AE group had the least proportion of PIFR in PIFR , 29. For in PIFR . All the1, total lung capacity (TLC), inspiratory capacity (IC) and a significant greater RV/TLC in the suboptimal PIFR group compared to the optimal PIFR group [1 or FEV1% predicted or FVC or CAT score [1, PEF and IC , and a weak negative correlation with mMRC score (r = -0.200). However, our attempt to construct a qualified prediction model for PIFR based on these factors was a failure. At this stage, it is still necessary to measure PIFR by In-Check DIAL® to guide inhaler choice.According to the study by Duarte et al., lung function measurements demonstrated a significant lower FEVFR group . By contAT score , 32. In In addition, a slow and deep inhalation is required when using pMDIs, and a PIFR greater than 90L/min is considered too fast. Some studies have proven the necessity to educate patients regarding correct pMDI technique , 34. Our1, PEF, IC and mMRC, but the correlation was not strong enough to indicate optimal PIFR to use specific DPIs. Besides, patients with AECOPD or asthma attack generally had suboptimal PIFRs and should be prescribed DPIs with caution.In general, a considerable number of outpatients with COPD or asthma were not able to achieve the optimal PIFRs for using DPIs. Inhaler education including training using In-Check DIAL® played an important role in improving patients’ PIFRs and we recommend that all patients who are prescribed inhalers should have their abilities evaluated and techniques trained. PIFR was associated with patients’ FEV


The diagnosis and health care of patients with rare diseases present a tremendous challenge worldwide. This study described the health care service utilization through participants’ perspective and estimated the cost of illness (COI), and patients with Gaucher disease (GD)’s/caregivers’ health-related quality of life in China.An online retrospective survey of patients with GD and their caregivers was conducted during May–June 2018. Socio-demographic, health service utilization, disease-related expenses, social support, sleep quality , and the Short Form Health Survey (SF-36) were investigated. Using self-reported information, we estimated the annual COI, including direct healthcare, direct non-healthcare, and indirect costs.Forty patients and their 49 caregivers were surveyed. The patients’ onset age of GD was 9.3 ± 10.9; their disease course was 3.5 ± 3.1 years. 21 (42.9%) patients had ≥ 2 caregivers, but 35 (71.4%) caregivers reported have no experience as a caregiver. 79.6% caregivers have stopped working, and 87.8% changed weekly working schedule. Before final diagnosis, patients visited 3.9 ± 3.1 (max = 20) hospitals and took 1.2 ± 1.7 (max = 6.6) years for confirmed diagnosis. On average, 5.0 ± 9.6 misdiagnoses occurred, and the per-patient diagnoses cost was USD ($) 7576. After GD confirmation, 8 (16.3%) patients received no treatment, 40 (81.6%) received pharmacotherapy, 10 (20.4%) received surgery, 38 (77.6%) received outpatient service , and 37 (77.5%) received inpatient service . Annual per-patient COI was USD ($) 49,925 . Average direct healthcare cost was $41,816, including pharmaceutical , inpatient , and outpatient . Productivity loss per-caregiver was $1,980, and their Zarit Burden Inventory score was moderate-severe (48.6 ± 19.6). Both patients/caregivers reported lower social support , two times higher PSQI , and half lower SF-36  than those reported for healthy Chinese individuals.The high misdiagnosis rate, together with delayed diagnosis, substantial costs, and deteriorated health-related quality of life of GD patients as well as their heavy care burden, calls for extreme attention from policymakers in China. Further efforts of government and society are urgently demanded, including pharmaceutical reimbursement, screening newborns, developing precise diagnostic tools, and training doctors.The online version contains supplementary material available at 10.1186/s13023-021-01963-6. Gaucher disease (GD), an ultra-rare multi-organ involvement, inherited recessive enzyme deficiency , 2, is sCurrently, the effective therapy for GD patients, such as enzyme replacement therapy and substrate reduction therapy, which must be administered continually, are extremely costly for patients and caregivers , 9. FurtThe World Health Organization has emphasized the need for urgent action to diagnose and treat people with rare diseases . HoweverThis study aimed to describe the health care service utilization through participants’ perspective, estimated the cost of illness, health-related quality of life of patients with GD, and the quality of life of their caregivers.An online retrospective survey of patients with GD and their caregivers was conducted for data collection. The inclusion criteria for patients were as follows: (i) a diagnosis of GD by a physician before the study; (ii) with a caregiver who was familiar with the whole treatment process of them; (iii) if the patient was under 15, with a voluntary caregiver to help answer all the real information of them. The inclusion criteria for the caregivers included that he/she was: (i) the primary caregiver ; (ii) was thoroughly familiar with the patient's disease; (iii) accompany patients every visit to the treatment; and (vi) was able to understand the content of the questionnaire.The China Gaucher disease family exchange group (C-GDFEG) is currently the largest GD information exchange platform in China. The questionnaire, including the patient part and the caregiver part, was distributed simultaneously to eligible patients with GD and their caregivers. In the case of patients < 15 years or patients who are dependent partly or on full-time care, the patient part asked whether the patient can answer independently, and questions were set up in two ways . The patient part was answered by themselves or with their caregivers’ help if they can understand questions; if not, patients’ information will be answered only by their caregivers.From the literature review, we identified key areas that were both important for the patients and families, and essential for the health authorities and service provision planning. The online self- administered questionnaire for the patients with GD, their caregivers, and their households comprised the following sections: (i) socio-demographic characteristics; (i) health service utilization ; (ii) cost of illness; (iii) social support; (iv) sleep quality; (v) care burden; and (vi) self-reported health (using SF-36).The patients’ socio-demographic characteristics included age, sex, current residence, mean age at onset, disease duration, type of GD, family history of GD, and caregivers’ number. Socio-demographic characteristics of the caregivers included the daily care time, experience of being a caregiver, stopped working because of patients’ GD, change of weekly working scheme because of patient’s GD, and members with chronic disease > 60/ < 5 years of age. Besides, whether living on minimum subsistence allowance or relatives' relief or not was also reported.The health service utilization data were collected in this study to assess patients’ diagnosis and treatment status. Health service utilization covering the 12 months health service utilization of patients with GD surveyed by self-designed questions, including the following: (i) the original reason to see the doctors; (ii) symptom; (iii) types of medical institutions frequently visited; (iv) the number of hospitals visited for GD diagnosis; (v) total cost of GD diagnosis; (vi) length before the final GD diagnosis was confirmed; (vii) misdiagnoses ; (viii) the number of misdiagnoses ; (ix) therapy after GD diagnosis; (x) outpatient/inpatient visit for GD; (xi) traffic time; and (xii) surgery/pharmacologic therapy after GD diagnosis.Additionally, caregivers’ perceptions, “the availability and affordability of therapeutic drugs,” “difficulties during GD treatment,” “knowledge of GD,” and “difficulties to get diagnosis information” were also investigated.Direct healthcare costs: (i) daily outpatient/inpatient treatment cost; (ii) laboratory and diagnostic costs; (iii) imported/domestic drugs’ costs; (iv) formal care cost; (v) other direct outpatient/inpatient medical costs; Direct non-healthcare costs: (vi) outpatient/inpatient costs for accommodation/transportation/meals; (vii) artificial nutrition costs; (viii) other direct non-healthcare costs; and Indirect costs: (ix) daily lost wages of caregivers.We retrospectively evaluated the total cost of GD, comprising direct healthcare, direct non-healthcare, and indirect costs for patients and their families. Costs comprised the following components: https://data.oecd.org/conversion/purchasing-power-parities -ppp.htm#indicator-chart.]Respondents were also asked to recall the use of resources: (i) outpatient/inpatient visit frequencies (consultations ) annually ; (ii) the average days for each outpatient/inpatient visit; and (iii) total days of lost wages annually. The resources used were multiplied by the corresponding unit cost to estimate the annual cost per patient, and the monetary values of the unit prices were reported in USD [$, Purchasing Power Parities in the study years of OECD National Accounts Statistics (2018): The subjective burden of the caregivers was measured by ZBI (22-item version), with item scores ranging from 0 (never) to 4 . The total score ranges from 0 to 88, and scores < 21 correspond to little or no burden while scores > 61 correspond to severe burden [SSRS comprises 10 items and includes three subscales: subjective support (4 items), objective support (3 items), and utilization of support (3 items). The total SSRS score ranges from 12 to 66 points, and higher scores indicate a higher level of social support .Sleep quality of individuals in 1 month was measured using the PSQI (comprises 19 items and 7 dimensions), which includes subjective sleep quality, sleep onset latency, total sleep duration, sleep efficiency, sleep disturbances, use of sleep medication, and daytime dysfunction. The sub-total of the scores of each dimension ranges from 0 to 3, and the maximum score is 21. The cut-off score for PSQI-defined cases of poor sleep quality is ≥ 6. A Chinese PSQI version has been validated with adequate reliability .Quality of life was measured by the SF-36 comprising 36 items, including the physical and mental component scores . SubscalDescriptive analysis was conducted to evaluate the social demographic characteristics, the status of health service utilization, cost of illness, and health-related quality of life. Continuous variables were presented as means ± SDs, and categorical variables were presented as absolute and relative frequencies. The 2.5 and 97.5% quantiles of the bootstrap distribution were used as the limits of the 95% CI. Subgroup comparisons of health-related quality of life and COI were conducted using student t-tests for two groups and one-way ANOVA tests for three or more groups. Correlation analysis were used to continuous variables. All statisitical analyses were conducted using SAS software, version 9.4 .From May to June 2018, we contacted a total of 98 families of patients with GD in C-GDFEG before conducting this survey. A total of eligible 51 (52.04%) patients enrolled in this study. Both the patient part and the caregiver part completely answered was considered as a valid questionnaire. Of them, 49  patients with GD and their caregivers (n = 49) completed the questionnaire were included in this study. The contact details of the researchers were also sent to the participants for information and further communication.Characteristics of enrolled patients with GD, families, and caregivers are shown in Table Among patients’ families  years for the diagnosis to be confirmed. The total cost for GD diagnosis was USD ($) 7575.8 (median); 59.2% of patients experienced ≥ 1 misdiagnosis, with a mean of 5.0 . Before the correct diagnosis, most patients were misdiagnosed with unexplained splenomegaly (65.5%), hypersplenism (44.8%), and hemophilia (10.2%). Eight (16.3%) patients received no health service following GD diagnosis. Ten patients underwent surgery . The remaining 40 (81.6%) received pharmacotherapy, among whom 14 (35.0%) had not used medications as prescribed, 27 (67.5%) reported using imported drugs, 9 took imiglucerase (the medicine used treatment of GD), and 5 were still using imiglucerase from the onset of GD diagnosis; all 49 (100%) agreed that the high price of medicine led to the failure of compliance with the doctor's prescription. Furthermore, 36 (90.0%) reported purchasing their medications at medical institutions or pharmacies, while 31 (71.5%) purchase from overseas.Additional file The cost of illness of patients with GD is shown in Table The average annual direct non-healthcare costs added up to $4,974.4 . With both direct healthcare and non-healthcare costs, the annual direct cost was estimated at $46,790.6. The indirect costs for GD primarily originated from the productivity loss to the caregivers while caring for patients with GD .(SSRS), Pittsburgh Sleep Quality Index (PSQI), and Short Form Health Survey (SF-36) scores for patients with GD, their caregivers, and norms of healthy Chinese people are shown in Table The total Social Support Rating Scale urvey SF-6 scores Besides, the health-related quality of life of the patients with GD and caregivers was assessed. Patients (39.4 ± 22.4) and caregivers (47.6 ± 23.0) reported a half lower Physical Component Summary than the normal values for healthy Chinese people . Further, Mental Component Summary in both patients (43.2 ± 16.1) and caregivers (45.4 ± 20.4) was significantly half lower than the normal values in healthy Chinese people .F = 4.634, P = 0.017), and GD patients taking medication as prescribed is significantly different with GD patients without . Duration of GD final confirmed diagnosis  and the difficulty to get diagnose  are positively relative to the COI of GD patients . The health condition of GD patients  is positive relative to the quality of life of GD patients . Patients with nervous system involvement symptoms are significantly different with non . Economic pressure  and difficulty in caring for GD patients  are negatively correlated with caregivers’ health-related quality of life. Health condition of GD patients  and the objective support received by GD caregivers  are positively related to the quality of life of GD caregivers  . The addHowever, both the availability and affordability of orphan drugs  for the Furthermore, to recoup research and development costs and for profit, orphan drug manufacturers often adopt a strategy of charging high prices . MiglustDue to the delayed diagnosis, unavailability, and unaffordability of costly drugs, 79.6% of 49 patients with GD felt poorly confident about future treatment. Moreover, the total social support, sleep quality, and quality of life scores for patients with GD/caregivers were significantly lower than those for normal healthy Chinese people. In this study, the health-related quality of life of GD patients with bone pain or other bone symptoms (31.58 ± 5.54) is significantly lower than patients who have non-bone pain symptoms (52.95 ± 22.72). Caregivers of type 1 GD patients have the highest health-related quality of life (51.29 ± 20.31), followed by caregivers of type 3 GD patients (40.01 ± 16.65) and caregivers of type 2 GD patients have the worst quality of life (23.38 ± 11.62). The health-related quality of life of caregivers of GD patients with nervous system involvement symptom (29.29 ± 11.52) is significantly lower than caregivers of non-neural system involvement GD patients (50.95 ± 18.49). Clinicians should pay more attention to GD patients accompanied by skeletal symptoms and nervous system involvement. Meanwhile, the more objective support caregivers received, the higher the health-related quality of life of GD caregivers. Due to the nervous system involvement of type 2 GD ; cliniciFirst, this study is limited primarily by the small sample size. Due to the rarity of GD, data collection was challenging. Second, families who voluntarily participate in the GD patient registry may represent a more compliant and motivated patient cohort in general. Thus, the findings may not be generalized to all. Thirdly, this study relied on responders’ recall of health service utilization and the unit costs to capture a more inclusive set of cost components usually not included in billing data, such as traffic costs, formal care costs, and productivity loss to caregivers. To enhance the accuracy of the estimates reported, patients with GD and caregivers were asked to complete questions regarding the average consumption amount and costs per resource in the past year. However, recall bias may have led to errors. Fourthly, utilization and corresponding costs from pharmaceutical use of prescription were not included in the survey. For pharmaceutical costs, we asked for the “annual purchase of imported/domestic medicines,” which could have resulted in an underestimation of this study’s GD’s financial burden. Hence, appraisal costs using data from health insurance is needed. Lastly, it was no possible to estimate informal care costs due to the form of the question we design to request this information, but we assessed the productivity losses of informal caregivers.Patients with GD often encountered the frustrating experience of high misdiagnosis rate, long-delayed diagnosis, substantial costs, and deteriorated health-related quality of life in China. For patients with GD, a rapid, precise diagnostic tool for earlier and timely definitive diagnosis of GD is urgently needed. Measures targeting improving the availability and affordability of orphan drug needs to be developed holistically in China. Furthermore, newborn screening for disorders that meet the criteria for population screening with reliable diagnostic tools should be explored. Besides, enhancing doctors’ ability in GD diagnosis and differential diagnosis, raising awareness of the early signs/symptoms or less severe manifestation to achieve earlier diagnosis and timely therapy of rare diseases, relieve caregivers’ burden, and provide much needed social support are essential. This research can facilitate greater societal awareness of rare diseases, help policymakers develop appropriate intervention programs, and inform healthcare-focused support schemes and policies for patients and their families.Additional file 1. Description/comparison of the characteristics, utilization of health service, perception of treatment, cost of illness, and scores of health-related quality of Gaucher disease (GD) families/caregivers/patients.


The purpose of this study was to identify the epidemiologic factors of panfacial fractures (PFs), and to evaluate the significance of anatomic PF categories and the Facial Injury Severity Scale (FISS) in classifying and standardizing panfacial injuries.A retrospective review of all patients treated with PFs at our institution between June 2010 and April 2021 was performed. PF was defined as a concurrent fracture in at least 3 of 4 facial subunits . Data regarding patient demographics, causes of injury, location of fractures, major concomitant injuries, and postinjury complications were collected, and the FISS score was collected from each patient. Statistical analysis was performed using IBM SPSS Statistics version 22.0.p = 0.018), the number of concomitant injuries (p = 0.014), and early surgical airway management (p = 0.003). Different PF patterns were significantly correlated with different types of concomitant injuries and complications. The FISS score showed a significant difference with PF patterns (p = 0.000) and sex (p = 0.007), and a FISS value of 11 or more is the appropriate cutoff for the prediction of multiple concomitant injuries and complications.A total of 227 patients were enrolled. The most commonly fractured bones were the maxillary sinus wall (92.1%), mandible (82.8%), and zygomatic arch (75.3%), and the most common fracture sites in PFs were graphically presented. Four PF patterns were defined: FULM (n = 60), FUL (n = 39), ULM (n = 127), and FUM (n = 1). There was a significant association between PF patterns and sex (Both the anatomic PF categories and FISS were significantly correlated with various concomitant injuries and complications. The combination of PF categories and FISS provided a better positive and negative prediction of concomitant injuries and complications for PF patients. Patients with FULM and FISS > 11 had an obviously higher proportion of the need for multiprofessional treatment.The online version contains supplementary material available at 10.1186/s12903-021-01900-w. Panfacial fractures (PFs) are often the result of high-energy injuries and present remarkable challenges to both surgeons and patients. These fractures are generally defined as fractures that simultaneously involve at least three out of four subunits of the facial skeleton, that is, the frontal area, upper and lower part of midfacial area, and mandibular area , 2. The The purpose of treating a PF patient is not only to save life but also to recover the structure, function, and aesthetics of the maxillofacial area while managing concomitant injuries effectively. The complex management of patients with multidistribution trauma requires a standardized classification for describing PF in a way that is comprehensive, measurable, validated and reproducible. Classifying PFs should be the first step toward a systemic approach for treating concomitant injuries and reducing complications , 7. TradThe use of a quantitative scale for facial fracture can be potentially beneficial, facilitating the proper treatment of concomitant injuries and complications and preventing irreversible damage. In addition, as a prognostic and predictive classification tool, it could simplify the communication among clinicians and patients about the extent of the injury , 11. AltAssessing and classifying PFs regarding concomitant injuries and complications will facilitate comprehensive treatment planning and multidisciplinary cooperation. However, such a well-developed clinical classification has yet to be reached. The purpose of the present retrospective study was to investigate the epidemiologic factors, concomitant injuries, complications, and FISS scores of PFs, and to verify the significance of anatomic PF categories and the FISS in classifying PF patients based on concomitant injuries and complications.A retrospective study was carried out from the data collected in hospital charts of facial trauma patients treated in the Department of Oral and Cranio-maxillofacial Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine between June 2010 and April 2021. The protocol of this study was reviewed and approved by the institutional review board of Shanghai Ninth People’s Hospital.The facial skeleton was divided into 4 subunits: frontal area, upper midface area, lower midface area, and mandible area Fig. . PatientAge/sex.Etiology of trauma: It was assigned as 6 categories: fall, interpersonal violence, automobile accident, bicycle/E-Bike accident, striking an object, and work accident.Fracture sites: The original computed tomography (CT) scan of each PF patient was reviewed to identify the exact fracture sites.Major concomitant injuries were classified into 5 categories: upper/lower limb injury, cervical spine injury, thorax injury, craniocerebral injury, and abdomen injury.Postinjury complications: Postinjury complications were analyzed for each patient.Facial Injury Severity Scale (FISS): The individual modified FISS score was calculated according to Erdmann et al. . The poiFor each PF patient, the emergency department chart, all clinic notes, all relevant radiology scans and reports were reviewed. The following data were collected for each patient:p < 0.05 was considered significantly different.Statistical analysis was performed using IBM SPSS Statistics version 22.0 . The chi-square test was used to determine the significant differences between fracture patterns, FISS scores and sex, cause of injury, number of concomitant injuries, complications, and early surgical airway management. Student’s t test was used to determine the significant difference between concomitant injuries, complications and FISS score values. The cutoff value of the FISS was determined by ROC curve analysis. A total of 227 PF patients were analyzed for the inclusion criteria and enrolled in this study. Of these patients, 198 were male (87.2%), 29 were female (12.8%), and the M/F ratio = 6.8/1. The average age of the patients was 36.2 ± 14.3 years, ranging from 4 to 75 years of age, and the most affected age group was 19–29 years (28.2%) , followed by the mandible (82.8%), zygomatic arch 75.3%), lateral orbital wall 74.9%), and nasal bone (69.6%). Additionally, the most common sites of mandibular fractures in PF were the symphysis/parasymphysis (52.9%), body (22.0%), and condyle (20.7%). The total number of each fracture site for each mechanism of injury is presented in Table %, latera.9%, and p = 0.339).Regarding the anatomic PF categories, four fracture types were defined, including FULM (n = 60), FUL (n = 39), ULM (n = 127), and FUM (n = 1). As shown in Table p = 0.014, Table p = 0.003, Table p = 0.024 and p = 0.000, respectively), while upper/lower limb injuries were positively correlated with the ULM type and negatively correlated with the FUL type of fractures .A total of 174 of the 227 patients had major concomitant injuries in other body parts. Traumatic craniocerebral injury was the most common concomitant injury, accounting for 46.3% of the patients in our cohort, followed by upper/lower limb injury 35.2%), thorax injury (34.8%), abdomen injury (9.7%), and cervical spine injury (8.8%). The FULM type had a high incidence of two or more categories of concomitant injuries, while the FUL type showed a higher correlation with no concomitant injuries , cerebral hematoma (p = 0.000), CSF leakage (p = 0.010), hypoacusis (p = 0.010), hypopsia/blindness (p = 0.024), and ocular movement limit (p = 0.010); FUL type showed a significantly positive correlation with diplopia (p = 0.001) and hypopsia/blindness (p = 0.004) and a negative correlation with traumatic facial palsy (p = 0.033) and malocclusion (p = 0.007), while ULM types showed a significantly positive correlation only with malocclusion (p = 0.015) and a negative correlation with other complications, such as ptosis (p = 0.015) and anosmia (p = 0.020).Of all the patients, 97.8% complained of postinjury complications. The most common complication was malocclusion (83.7%), followed by limited mouth opening (67.4%), infraorbital nerve palsy 45.8%), and hypopsia/blindness 31.7%) , craniocerebral injuries (p = 0.027), and abdomen injuries (p = 0.031), and complications, such as hypoacusis (p = 0.004), cerebral hematoma (p = 0.024), anosmia (p = 0.002), and early surgical airway management (p = 0.000). Moreover, we performed ROC curve analysis to determine the value of the FISS score for the prediction of major concomitant injuries in patients with panfacial trauma, and the optimal cutoff value for the FISS score was 10.5 . In terms of the PF patterns, the FULM type was significantly more dominant in males than the FUL and ULM types. The most common etiology for all types of fractures was automobile traffic accidents, which was consistent with other studies. Work accidents were the second most common cause of FULM and ULM types, and bicycle/E-bike accidents were the second most common cause of FUL types. In addition, falls were another frequent cause, especially for the ULM type. Road traffic accidents such as automobile accidents and bicycle/E-Bike accidents are both correlated with injuries at high velocity and impact; accordingly, efforts should be made to increase traffic safety to reduce the incidence of these injuries.According to the multicenter study conducted by Brucoli et al., the most frequent cause of maxillofacial injury was fall, while zygomatic fractures were the most frequently encountered injuries. Falls from a height were associated with a low FISS value with no associated concomitant injuries, while concomitant injuries were seen in 27.3% of patients. The study emphasized the frequency of involvement of females, and the high frequency of zygomatic fractures –24. An aPFs are frequently associated with various life-threatening concomitant injuries and complications, the causes of which are usually large external forces –5. HwangAnother finding in the present study was that the FISS can be applied to evaluate the risk of concomitant injuries and complications of panfacial injuries. At present, a number of facial injury severity systems have been proposed, such as the Craniofacial Disruption Score (CDS) , MaxilloIn the present study, we revealed that both the anatomic PF categories and FISS were significantly correlated with several concomitant injuries and complications. The combined assessment of these two variables was then performed in an attempt to further propose a better prediction of concomitant injuries and complications for panfacial injury patients. As expected, our modified model provided a more accurate correlation between panfacial fractures and concomitant injuries or complications. Additionally, the heat map presented a good positive and negative predictive visualization of concomitant injuries and complications. Canzi et al. , 32 deveIn the present study, we investigated various factors associated with PFs, including patient demographics, causes of injury, location of fractures, major concomitant injuries, and postinjury complications. The most common fractured bones of PFs were the maxillary sinus wall, mandible, zygomatic arch, lateral orbital wall, and nasal bone. Traumatic craniocerebral injury, limb injury, and thorax injury were the most common concomitant injuries. There was a significant association between PF patterns and sex, concomitant injuries, early surgical airway management, and complications. Different PF patterns were significantly correlated with different types of concomitant injuries and complications. The FISS score also showed a significant difference with PF patterns, sex, concomitant injuries and complications. A FISS value of 11 or more is the appropriate cutoff for the prediction. We further proposed that the combination of PF categories and FISS can provide a better positive and negative prediction of concomitant injuries and complications for PF patients. It is suggested that this combined model could be a potential tool for the classification of PFs and therefore for the integration of multidisciplinary teams. Classifying PFs should be the first step toward systemic treatment.Additional file 1. Supplementary statistical analysis.