P = 0.0015). After adjustment for other markers in the stepwise Cox regression model, MGUS was still related to the increasing risk of MACE incident . Then, we constructed the nomogram based on the Cox regression model, and the concordance index (C-index) was 0.667. Hence, MGUS might be added into the risk model of CAD.We performed a retrospective cohort study to analyze all 87 CAD patients with MGUS and 178 CAD patients without MGUS admitted in Zhongshan Hospital Fudan University from 2015 to 2017. Patients were followed up via regular patient visits or telephone, and the median follow-up period was 2.9 years. The end point of follow-up was the occurrence of major adverse cardiac events (MACE). CAD patients with MGUS had a higher risk of MACE than those without MGUS (log-rank The online version of this article (10.1007/s12265-019-09950-w) contains supplementary material, which is available to authorized users. Plasma cell disorders, also called monoclonal gammopathy, are verified to be premalignant and malignant disorders characterized by monoclonal proteins secreted by clonal plasma cells and immunological homogeneity on electrophoresis. Plasma cell disorders consist of many pathological conditions, including monoclonal gammopathy of undetermined significance (MGUS), solitary plasmacytoma, multiple myeloma (MM), amyloidosis, Waldenström macroglobulinemia (WM), and POEMS syndrome. Among them, MGUS is the most common disease. According to the research from Mayo Clinic in 2012 , 4.In our hospital, serum protein electrophoresis (SPEP), the monoclonal-protein screening test, is routinely incorporated into liver biochemical and function tests. Hence, all patients having liver function examinations are indeed screened for monoclonal proteins simultaneously in our institute. With routine SPEP screening, we have the unique opportunity to observe the prevalence of monoclonal gammopathy in the large-scale hospital population and to identify patients with MGUS. If the abnormal band is found via SPEP, physicians should perform the serum immunofixation electrophoresis (IFE) to confirm the existence, the concentration, and the type of monoclonal proteins . To accoAs a geriatric disease, the diagnosis of MGUS might be simultaneously established with coronary artery disease (CAD). In our daily clinical work, we found a surprising phenomenon that these patients seemed to experience worse outcomes than CAD patients without MGUS. The hypothesis was supported by the abnormal ratio of serum free light chain (FLC) in MGUS patients . High FLn = 6757) with positive SPEP from January 1, 2015 to December 31, 2017 at Fudan University affiliated to Zhongshan Hospital. The serum IFE was performed to confirm the presence of monoclonal gammopathy in these patients. Among these patients (n = 2046) with positive IFE, the diagnosis of MGUS was determined according to the diagnostic criteria. Only patients with unexplained anemia  or renal insufficiency (serum creatinine was more than 177 μmol/L) [n = 952), some (n = 87) also suffered from CAD confirmed by the coronary angiogram.We enrolled all inpatients and outpatients ( μmol/L) . The comn = 178) without MGUS were enrolled during this period at Zhongshan Hospital. The exclusion criteria were the absence of coronary angiogram, non-obstructive CAD patients, and coronary angiography showing less than 50% stenosis without a history of coronary revascularization.A random number function were used to select half a month  from 3 years (2015–2017), and all CAD patients .Clinical and biochemical information of these patients were collected, including age, gender, diagnosis, smoking status, history of CAD, stent numbers, ejection fraction, the type, and concentration of monoclonal protein; values of serum glucose, Hb1Ac, estimated glomerular filtration rate (eGFR), cardiac troponin T (cTNT), low-density lipoprotein (LDL), C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and coagulation function containing activated partial thromboplastin time (APTT), prothrombin time (PT), and fibrinogen. Among them, numbers of stent were to evaluate the severity of CAD. Informed consent was obtained from all patients in Zhongshan Hospital. Fudan University affiliated Zhongshan Hospital Ethics Committee approved this study, and our research was conformed to the principles outlined in the Declaration of Helsinki.The consecutive variables were analyzed by Mann-Whitney U test or t-test. Categorical outcomes were compared through chi-square test. The multiple linear regression models were performed to investigate the impact of MGUS on NT-proBNP and cTNT, which were demonstrated as the most important markers in prognosis of CAD patients –20. The P < 0.05 was regarded as statistical significance.All statistical tests were two-sided, and the analysis was made by SPSS 21 software  and R software, Version 3.6.0 . All 952 MGUS patients at Zhongshan Hospital from January 1, 2015 to December 31, 2017 were enrolled. The participants included 649 males and 303 females, and the median age was 66 . Among them, 19 (2.0%) of the patients had light chain MGUS, 629 (66.1%) had IgG MGUS, 92 (9.7%) had IgM MGUS, 178 (18.7%) had IgA MGUS, and 34 (3.6%) had biclonal gammopathy or triclonal gammopathy. About 769 patients with MGUS had concomitant diseases, including 384 cardiovascular diseases , 193 gastrointestinal and hepatobiliary diseases , 145 urinary diseases (54 chronic kidney disease), 131 respiratory diseases , and so on.P = 0.032) and age (P = 0.003) were demonstrated to be statistically significant, and there existed no difference of stent numbers between MGUS group and non-MGUS group, illustrating that the CAD severity of MGUS patients was similar with that of non-MGUS patients. Besides, 99 underwent coronary angiography among 952 MGUS patients, and 12 were confirmed without 50% stenosis and 87 with at least 50% stenosis. When it comes to 199 non-MGUS patients experiencing coronary angiography, 21 were confirmed without 50% stenosis and 178 with at least 50% stenosis. There existed no difference in the frequency of patients who underwent angiography but did not have significant stenosis between MGUS group and non-MGUS group (P = 0.165), also demonstrating that MGUS patients and non-MGUS patients had similar CAD severity.Table P = 0.0015)  after eliminating the influence of other high-risk factors in CAD patients.In our research, all 265 CAD patients (87 with MGUS and 178 without MGUS) were followed up with the median period of 2.9 years, and 60 MACE incidents were observed, including 4 cases of myocardial infarction, 42 cases of coronary revascularization, 12 cases of deaths, and 2 cases of stroke. The results indicated that the CAD patients with MGUS experienced a higher risk of MACE than those without MGUS , stent numbers (P = 0.045), eGFR (P = 0.023), and fibrinogen (P = 0.049) were independently related to the outcomes of CAD patients. CAD patients with MGUS had significant higher probability of experiencing MACE  compared with those without MGUS even after eliminating the influence of other risk factors, including gender and age.To quantify the effects of risk factors on the incidence of MACE and to clarify the independent influence of MGUS, the multivariate stepwise Cox regression model with the minimum AIC Table  was perfThen, the nomogram Fig.  was geneP = 0.022), which was confirmed to be one of the most important risk factors in the coronary artery disease [To our knowledge, this is the first research to illustrate the role of MGUS in the prognosis of CAD patients. The first important finding was that CAD patients with MGUS had worse prognosis than those without MGUS. The second significant finding was that MGUS had an independent influence on the value of NT-proBNP P = 0.0, which w disease . FurtherP = 0.165). It was more accurate to predict non-MACE probability of 2- and 3-year using model 2, and the predictive accuracy was similar in 1-year prediction . Perhaps, we will be able to figure out whether there is correlation between FLC and worse prognosis of CAD patients when we get enough data in the future.It was assumed that abnormal free light chain and high blood viscosity might be two reasons why CAD patients with MGUS experienced worse prognosis. The serum free light chain (FLC) referred to the light chains (κ and λ) which were unbound to heavy chains in the serum , and theFurthermore, there was an increase in the blood viscosity in patients with MGUS compared with healthy population . This phFinally, MGUS becomes popular in China with the growth of aging population and improvement of detection methods. The prevalence in individuals older than 50 year old has increased to more than 4% –35. In tFig S1(PNG 1319 kb).High Resolution Image (TIFF 3750 kb).Fig S2(PNG 3392 kb).High Resolution Image (TIF 348 kb).Fig S3(PNG 1378 kb).High Resolution Image (TIF 302 kb).Table S1(DOCX 14 kb).Table S2(DOCX 14 kb).Table S3(DOCX 12 kb).


We aimed to identify which part of the patients with metastatic renal cell carcinoma (mRCC) is not suitable for cytoreductive nephrectomy (CN).The data of mRCC patients was acquired from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate cox regression analysis and nomogram were performed for selecting factors independently associated with survival. Propensity score matching (PSM) was applied to reduce potential bias when comparing survival of mRCC patients treated by CN or non-surgery (NS). The survival analysis of subgroups was estimated by the Kaplan–Meier method and compared by log-rank testing. The summary of subgroup analysis was showed by forest plots.The records of 21,411 patients with mRCC were obtained from the SEER database. After screening, a total of 6532 patients were included for further analysis, of which 6043 underwent CN and 489 underwent NS. Age, T stage, N stage and tumor size were involved in subgroup analysis by PSM according to the result of multivariate cox regression analysis and clinical experience. Survival benefit was not found in T4 stage patients. Further analysis showed that T4&N1 and T4&age ≥ 76 yr subgroups could not obtain survival benefit from CN.CN should not be performed in T4 stage mRCC patients who were in status of N1 stage or older than 76 years, because surgery cannot take significant survival benefit for them. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and 90–95% of kidney neoplasms, 25–30% of patients present with metastatic disease at time of diagnosis. Metastatic RCC (mRCC) is one of the most treatment-resistant malignancies and its prognosis is generally poor and median survival after diagnosis is very short . CytoredA research demonstrated that large benefit exists in both overall survival (OS) and progression- free survival (PFS) in patients receiving a CN compared with those without, even after adjusting for imbalances . The latThe SEER database is a cancer-based registry sponsored by the NCI  which incorporates high quality data derived from 18 cancer registries and covers approximately 27.8% of the U.S. population (based on the 2010 census) . We idenVariables were obtained using the SEER registries. These variables included sex, race, age at diagnosis, derived AJCC T, 6th ed. (2004–2015), derived AJCC N, 6th ed. (2004–2015), derived AJCC M, 6th ed. (2004–2015), RX Summ–Surg Prim Site (1998+), CS tumor size (2004+), SEER cause-specific death classification, Survival months, vital status recode (study cutoff used), Reason no cancer-directed surgery.P values and the maximum chi-square of log-rank tests by using X-Tile 3.6.1 software  [The main process of PSM was divided into three steps. At first, continuous variables such as age at diagnosis and tumor size were transformed into categorical variables to identify the best cut-off point based on the lowest versity) . Secondlp-value < 0.05 was considered significant.We compared the cancer specific survival (CSS) among subgroups of mRCC patients treated by CN or NS, using PSM. Then we verified the results by comparing overall survival (OS) between patients treated by CN or NS. Continuous variables were compared with the Student’s t-test. Unordered categorical variables were compared by chi-square tests. Ordered categorical variables were compared by Goodman and Kruskal’s gamma. If the expected frequency was less than five, Fisher’s exact tests were used. The Mann-Whitney U test was applied to compare variables that did have an unnormal distribution. Cumulative survival was estimated by the Kaplan-Meier method and compared by log-rank tests. Statistical analysis was achieved by packages of R software (3.5.3), including MatchIt, tableone and survival. All tests were two sided; We identified 21,411 mRCC patients with ICD-0-3 primary site code C64.9 and M1 stage. Among them, 8478 patients were recommended for surgery. Only 7515 patients meted the code of RX Summ--Surg Prim Site 0 (NS), 40 (CN) or 50 (CN). Then 449 pitients with TX and 428 patients with NX were excluded. After that, 106 cases with unknown, abnormal or inaccurate tumor size were excluded . Finally, a total of 6532 cases which met our inclusion criteria were retrieved, including 6043 that underwent CN and 489 cases that received NS. Table P < 0.0001) and 82 mm , respectively. According to the latest guideline and for the convenience of analysis, we unified N2 and N1 in derived AJCC T, 6th ed. (2004–2015) as N1. Nomogram plot in Fig. P = 0.01), age (P = 0), race (P = 0.02), T stage (P = 0), N stage (P = 0) and tumor size (p = 0) were independent risk factors for CSS of total mRCC patients. Therefore, in the next subgroup analysis, the PSM was performed for balancing sex, race, age, tumor size, T stage, and N stage in CN- or NS-treated mRCC patients.Through X-Tile, we figured out the best cut-off points for age at diagnosis and tumor size as 76-years-old .First, we compared the CSS of mRCC patients treated by CN or NS for subgrouping under each variable . Other variables were balanced by PSM to reduce potential confounding effects and treatment selection bias when comparing subgroup of one variable. Survival benefits were found in patients treated by CN in almost all subgroups except T4 subgroup. Although there were 8 months benefit of median CSS time in T4 subgroup patients, the HR (95% CI) was 0.801 to 1.816, crossing 1 Fig. . This waIn order to further explore which factors may prevent patients of T4 subgroup from benefiting from CN, we matched T4 stage with age, N stage and tumor size respectively to group them in more detail Fig. . Table 2Various treatments have been proposed for mRCC. The use of CN in the immunotherapy era was based on two randomized trials conducted by the European Organization for Research and Treatment of Cancer and by the Southwest Oncology Group , 9. In tIn the present study, we compared cancer-specific survival among different subgroups of mRCC patients treated with CN or NS, after balancing other variables impacting survival. A special and important inclusion criterion is that all patients must be recommended for surgery by doctors. We found that the CSS of CN patients was better than that of NS patients in almost all subgroups under each variable, which confirmed the value of CN in clinical treatment. Only the patients of T4 subgroup cannot obtain cancer specific survival benefit from CN. Further analysis suggested that age and N stage were two risk factors under T4 stage. T4 stage Patients who were in status of N1 stage or older than 76 years of age cannot benefit from CN. In terms of overall survival, patients in these subgroups were still unable to benefit from CN. Therefore, CN is not suitable for this part of patients. When faced with these patients, we should carefully consider how to choose the most appropriate treatment.To help oncologists and surgeons assure the best indication for CN and avoid unnecessary surgery, the method of preoperative identification is urgently needed. Previous study has shown that patients with high or intermediate scores can acquire survival benefit from CN under the MSKCC criteria. In addition, according to the ECOG score standard, only patients with a score of 0 or 1 can benefit from CN . Culp etThe current study exists several limitations. First, SEER data may be limited by unrecorded variables, underreported and incomplete data, variations in data coding and reporting, and migration of patients in and out of the SEER registry area. Second, there was no available detailed information of systemic therapy such as targeted therapy, chemotherapy, and immunotherapy for the cohort of mRCC patients. We did not know whether systemic therapies between the CN and NS groups were balanced. Third, there was no unified criteria for patients who were recommended CN. This may lead to the instability of the included data and affect the final analysis results. Fourth, the selection bias between CN and NS groups could not be completely eliminated by PSM because there was a wide gap in the sample amount between the two groups and the clinical information included in PSM was limited. Fifth, the AJCC TNM stage of our data is 6th edition while several modifications in T and N stages have been made in the 8th edition. When applying the results of this study, the differences between different versions should be taken into account. Sixth, the small sample size of some subgroup after PSM may lead to inaccuracy and randomness of the results.CN should be performed in all patients who under T1, T2 or T3 stage because they can obtain survival benefit from surgery. In T4 stage, N1 and age ≥ 76 yr are two high risk factors. Patients who are in T4&N1 subgroup or T4&age ≥ 76 yr subgroup cannot benefit in CSS from CN significantly. In the face of T4 stage mRCC patients, we should choose the treatment therapy carefully and CN is not recommended as the first-line strategy.


Preterm infants are at risk for structural disruption of brain connectivity due to perinatal complications encountered during the fetal and neonatal periods. This study aimed to investigate the development of connectivity using diffusion tensor imaging at near-term age and the effect of grade 1 intraventricular hemorrhage on it.A total of 86 infants  without apparent brain injury underwent diffusion magnetic resonance imaging (MRI) between 36 and 41 weeks post-menstrual age. The diffusion-MRI based connectomics were constructed from 64-segmented regions by using the Johns Hopkins University neonate atlas and were weighted with fractional anisotropy. The connectomes were quantified in the structural networks and investigated using network metrics, such as the clustering coefficient, local efficiency, characteristic path length, global efficiency, and small-worldness. We compared the differences in the brain networks of preterm infants with or without grade 1 intraventricular hemorrhage in binary and fractional anisotropy-weighted (wFA) connectomes.p = 0.027) and local efficiency , implying the potential for segregation. However, the preterm infants with intraventricular hemorrhage revealed a longer path length  and lower global efficiency , indicating a decreased integration in the wFA connectivity matrix than those without germinal matrix hemorrhage, after correcting for gestational age, sex, bronchopulmonary dysplasia, and age at scan.The 55 preterm infants had a mean gestational age at birth of 29.3 ± 4.1 weeks and the 24 term-born infants, 38.1 ± 1.1 weeks. A total of 13 of the 55 preterm infants (23.6%) were diagnosed with grade 1 intraventricular hemorrhage. The development of connectivity of the brain network in preterm infants without intraventricular hemorrhage was comparable at near-term age to that in term infants. The preterm infants with germinal matrix hemorrhage exhibited higher clustering (0.093 ± 0.015 vs. 0.088 ± 0.007, Grade 1 intraventricular hemorrhage in preterm infants may enhance the capacity for local information transfer and the relative reinforcement of the segregation of networks at the expense of global integration capacity. Advances in neonatal intensive care have markedly enhanced the survival rate and decreased the rates of intraventricular hemorrhage (IVH) in preterm infants , 2. AlthPreterm infants are at risk for structural disruption of brain connectivity due to the perinatal complications encountered during the fetal and neonatal period. Research has been conducted on the value of structural brain networks ascertained with diffusion MRI to predict the functional impairments and neurodevelopmental outcomes in very preterm children , 8. RelaIVH is an important cause of neurological and cognitive complications and can significantly impair brain development . SeveralThis study is part of a prospective observational cohort involving the postnatal follow-up of preterm infants at Hanyang Inclusive Clinic for Developmental Disorders in Hanyang University College of Medicine between December 2016 and June 2018. The institutional review board at Hanyang University Hospital approved the study protocol and scanning procedures, and informed consent was obtained from the parents of all children included in this study. The inclusion criteria for preterm infants consisted of the following: birth at < 35 weeks of gestation without major congenital malformations, no evidence of intraventricular or intracranial hemorrhage greater than grade I, no evidence of intrauterine growth retardation, and availability of MRI at near term age between 36 and 41 weeks postmenstrual age (PMA). Neonates with grade 1 IVH were included in our study. All cranial ultrasound scans and subsequent MRIs were evaluated for brain injury by a single pediatric radiologist. Early cranial ultrasound scans were performed within 3 days of birth and at 1 and 3 weeks later. Subsequent MRI scans conducted at near-term age were assessed for brain injury in preterm infants, including IVH, overt white matter injury, and cystic periventricular leukomalacia (PVL). We excluded 14 infants with evidence of intraventricular or intracranial hemorrhage greater than grade I, 1 infant with cerebellar hemorrhage, 2 infants with punctate white matter lesions, and 11 infants with poor image quality due to motion artifacts.We performed MRI imaging in healthy, term infants (between 37 and 42 weeks gestation) with uneventful deliveries from the same hospital, after informing the parents in writing and obtaining their consent. The 24 healthy, full-term infants with normal MRI and neurologic examination results were included as controls. The following exclusion criteria for full-term infants were used: prolonged intensive care (> 7 days), neonatal asphyxia, congenital infection, and congenital heart disease. Controls and preterm infants were imaged during natural sleep without sedation. Prenatal and neonatal data were prospectively recorded, including maternal details, gestational age (GA), birth weight, delivery type, sex, head circumference at scan, germinal matrix hemorrhage, culture-proven sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia (BPD). IVH was determined using the grading system established by Papile et al. . and was2; number of diffusion gradient directions, 15; TR/TE, 5243/76 ms; 40–50 axial slices; 2.0-mm thickness; field-of-view, 150 mm; matrix size, 1.97 × 1.97; total acquisition time, 6.5 min.T1- and T2-weighted imaging and DTI scans were acquired with a 3.0 T MRI scanner  and a 16-channel SENSE head coil. The MRI data were obtained at the age of 36–41 weeks PMA in preterm infants and at 37–40 weeks PMA in full-term infants. The T1- and T2-weighted images were obtained with sagittal T1 Turbo field-echo sequences (repetition time [TR]/echo time [TE] 8.2/3.8 ms) and Turbo spin-echo (TR/TE 4800/90 ms) sequences, respectively. The DTI sequence parameters consisted of the following: SENSE factor, 2; b value, 800 s/mmhttp://www.fmrib.ox.ac.uk/fsl). The eddy current distortion and head motion for individuals were corrected using FMRIB’s Linear Registration Tool (FLRIT) [dsi-studio.labsolver.org) [Diffusion-weighted imaging (DWI) data were preprocessed using the Diffusion Toolbox (FDT) from the FMRIB’s Software Library ( (FLRIT) , 21. The (FLRIT) . The dif (FLRIT) . The scaver.org) . The FA ver.org) . We usedver.org) , 27. Finver.org)  while thver.org) .Fig. 1Tp) and global efficiency (Eglob). The shorter path length and increased global efficiency in structural networks suggest the potential integration for effective connections. In contrast to network integration, network segregation refers to the degree to which the network is organized as clusters of sub-networks. Segregation indicates the relative strength of within-network connections compared to integration, and the most popular measures of segregation are clustering coefficient and local efficiency. Finally, small-worldness reflects both integrated and segregated information processing. The descriptions and definitions of these network metrics for a given graph G with N nodes are provided in Table http://www.brain-connectivity-toolbox.net).At a global level, connectomes were quantified in the structural networks and investigated using various network metrics, including integration measures, segregation measures, and small-worldness. Topological organizations of neonatal structural networks were characterized using the Brain Connectivity Toolbox in MATLAB  . The netSPSS 21.0  software was used for statistical calculations. We used the Mann-Whitney U-test and Fisher’s exact test to compare the clinical variables between groups. The preterm infants were sub-categorized into three groups as extremely preterm (< 28 weeks), very preterm (28 to 32 weeks), and moderate to late preterm (33 to 36 weeks). Mean network parameters in the preterm sub-groups were compared using the analysis of variance and general linear models with sex, BPD, and age at scan as covariates. Analysis of covariance was performed to confirm the differences in networks between preterm and full-term infants. Additional statistical analysis between preterm infants with and without grade 1 IVH was performed using general linear models with GA, sex, BPD, and age at scan as covariates to compare the structural network metrics, including clustering, local efficiency, path length, global efficiency, and small-worldness.p < 0.001) and featured a lower proportion of males .The total population consisted of 55 preterm infants 26 males) with a mean GA at birth of 29.3 ± 4.1 (range 23–35) weeks and a mean age at scan of 37.2 ± 1.4 (range 36–41) weeks, and 24 term-born infants  with a mean GA at birth of 38.1 ± 1.0 (range 37–40) weeks and a mean age at scan of 39.8 ± 0.9 (range 37–41) weeks. Table 6 males wp = 0.002) and birth weight . However, the age at the MRI scan and head circumference at age of MRI scan were not significantly different between preterm infants with and without grade 1 IVH. During the neonatal period, preterm infants with grade 1 IVH differed in that they exhibited a high rate of BPD  and a longer duration of total parenteral nutrition days . This is associated with chronic intubation and poor nutritional support for proper brain growth; however, these differences were insignificant.Relative to the preterm infants without grade 1 IVH, preterm infants with grade 1 IVH exhibited a low mean GA , very preterm , and moderate to late preterm . These exhibited no significant differences among preterm sub-groups in the statistical analyses, controlling for sex, BPD, and age at MRI scan as covariates in preterm infants. Table p < 0.001) and featured a lower proportion of male infants . The preterm neonates without grade 1 IVH exhibited slightly lower wFA clustering coefficients , and wFA local efficiency  than full-term infants. However, the clustering, local efficiency, path length, global efficiency, and small-worldness in preterm infants without grade 1 IVH were comparable to those in full-term infants after adjusting for GA, sex, BPD, and age at scan. Remarkably, the preterm infants with grade 1 IVH exhibited higher clustering  and local efficiency , implying the potential for segregation. However, they exhibited longer path length  and lower global efficiency , indicating a decreased integration in the wFA connectivity matrix among preterm infants with grade 1 IVH than those without grade 1 IVH, after correcting for GA, sex, BPD, and age at scan. In contrast, we observed no significant differences in the binary network parameters with and without grade 1 IVH.Table Developmental connectomics obtained from advanced neuroimaging techniques have emerged as an important tool for the characterization of the structural and functional brain connectivity during the early period of life in neonates. We explored potential alterations in structural network properties related to grade 1 IVH in preterm infants. The measures of structural segregation, such as modularity and local efficiency, were observed to increase, while global efficiency decreased in preterm infants with grade 1 IVH compared with those without grade 1 IVH, indicating a specialized reinforcement of network segregation at near-term age.Previous studies have reported the effects of grade 1 IVH on the developmental white matter microstructure in preterm infants. Morita et al.  observedThe beginning of the development of the microstructure of white matter connections and the emergence and establishment of small worldness reportedly occurs throughout 30 PMA , 10, 26.We explored the significance of the weighted networks and the differences between binary and FA-weighted networks. Discrepancies between unweighted or weighted connectome pipelines might be attributed to the differences in the speed at which networks change during dynamic developmental phases along with the abundant formation of new connections. To a lesser extent, differences in edge weights may account for the discrepancies. Compared to the binary approach, the FA-weighted approach could be more sensitive to the network organization of atypical early neural development in preterm infants than to the early development of the full-term brain . Our obsBall et al.  demonstrDespite these limitations, knowledge of the neonatal human connectome may provide insight into preterm development and the influence of grade 1 IVH on brain development at near-term age. Further follow-up studies based on structural brain networks should examine whether long-term neurodevelopment in preterm infants with grade 1 IVH is mitigated by delayed or altered integration and segregation compared to that in full-term infants.


Prostate cancer patients are known to suffer from poor sexual and urinary long-term side-effects following treatment, potentially impacting quality of life. The purpose of our study was to compare health-related quality of life at 3 years between prostate cancer patients and healthy controls according to key life-style characteristics. Secondary objectives were to compare urological dysfunction, sexual function, anxiety and depression.Multicentric, case-control, observational prospective, open, follow-up study including 819 prostate cancer patients < 75 years old from the EPICAP cohort, newly diagnosed from 1 December 2011 to 31 March 2014 and 879 healthy controls. Participants were excluded if they experienced a relapse. Controls from the same geographical region were age-matched and were excluded if they were diagnosed with prostate cancer. Patients received one of the following treatments: active surveillance (AS), radical prostatectomy (RP), external beam radiotherapy (EBRT), High-intensity Focused Ultrasound (HIFU), chemotherapy (CT), or androgen deprivation therapy (ADT) as appropriate. The primary outcome was the quality of life as evaluated by the QLQ-C30 questionnaire. Scores were analyzed by multivariate analysis to adjust for predefined socio-demographic confounding effects.p = 0.71). Multivariate analysis showed poorer social functioning in patients , more dyspnea , and yet less current pain .In total, 564 participants were included (mean age 67.9 years): 376 patients and 188 controls. Treatment breakdown was: 258 underwent RP, 90 received EBRT, 52 brachytherapy or HIFU, 15 CT, 26 ADT and 61 AS. There was no difference in median global quality of life between patients and controls (94.87 vs 94.15, Global health status score at 3 years after diagnosis was similar between patients and controls, though patients showed a significantly worse social functioning. Prostate cancer diagnosis per se does not seem to impact the quality of life of patients < 75 years at diagnosis. However, the therapeutic option that will be chosen following diagnosis should be carefully discussed with the medical staff in terms of benefit-risk ratios as it could have a long-term impact on urinary or erectile dysfunction.NCT02854982. Registered 4 August 2016, retrospectively registered.clinicaltrials.gov,  Prostate cancer (PCa) diagnosis and treatment are known to impact patient short-term quality of life (QoL) and functional symptoms . HoweverA recent review showed that QoL of newly diagnosed PCa patients was independent of the type of treatment, but that surgery had a negative impact on urinary continence and sexual function, and external beam radiotherapy (EBRT) on bowel function; active surveillance (AS) had the lowest impact on disease-specific QoL . These sOur study investigated QoL following PCa in the EPICAP cohort  to evaluStudy design and setting: EPICAP-QALY is an ancillary study of the EPICAP survey . EPICAP Participants: All participants from the EPICAP cohort completed a screening questionnaire to determine eligibility. Patients who had received hormone therapy within the previous year or who experienced a relapse in the intervening years were excluded, except patients on salvage radiotherapy following prostatectomy for more than 6 months with a PSA level < 1 ng/ml. Age-matched ±1 year healthy controls were included in a 1:2 ratio. Individuals diagnosed with PCa following inclusion or with a PSA > 10 ng/ml were excluded. Men with PSA > 10 ng/ml at the time of completing the questionnaire were not selected to exclude potential relapse for cases or cancer occurrence for controls.Outcomes: The primary outcome was QoL 3 years after PCa treatment compared to controls, as evaluated by the QLQ-C30 questionnaire . SecondaThese questionnaires were used to compare QoL and symptoms according to active surveillance (AS), radical prostatectomy (RP), EBRT, brachytherapy or High-intensity Focused Ultrasound (HIFU), androgen deprivation therapy (ADT) or combined care (CC). A life situation questionnaire complemented with specific questions concerning sexuality was used to test for some potential confounders .Data collection: Age, BMI, PSA level, educational level, housing, living alone, marital status, monthly income, chronic disease and regular medication were collected. Treatment at diagnosis, last treatment received, hormone therapy within previous 12 months, and employment status were also recorded. For controls, urologic consultation for urinary troubles, prostate treatment and PSA testing in the 3 previous year were recorded.Sample size: By predicting a lower participation rate in cases than controls and a recurrence rate of cases of 10%, we originally planned a cohort of 600 patients and 300 controls paired with a ratio 2:1 on age to highlight a standardized difference in score on the QLQ-C30 of 0.25  with a Statistics: The comparability of age was assessed with a Student test. Descriptive statistics are reported as counts and percentages for categorical variables and means and standard deviations for continuous variables with normal distribution and median and quartiles for others. Comparisons of baseline characteristics and putative risk factors between cases and controls were performed with Mann–Whitney, Kruskal–Wallis, χ2, Student, or Fisher exact test as appropriate.For each questionnaire, the distribution of scores was analyzed. When extreme values (0 or 100) were over-represented, scores were recoded into classes and described qualitatively with effectives and percentages.The univariate analysis was performed with a mixed linear model for quantitative scores . For recoded QLQ-C30 scores, analyses were conducted with a mixed logit model. To account for pairing, a random effect on 2: 1 trinoma was considered.For recoded QLQ-C30 scores, distribution and links with social potential confounders was assessed. When the symptom or trouble was present in less than 20% of cases or when no apparent link was possible, multivariate analysis was not performed. For other QLQ-C30 scores and for the summary quantitative score, the effects of putative confounders were evaluated. Socio-professional integration items were selected for testing based on their reliability, their clinical pertinence of potential confounding factors and their similarity with items of the QALIPRO study . PutativP-value lower than 0.20 were considered as potential covariates and adjusted mixed linear general models or logistic models were computed with a random effect on 2:1 trinoma.All variables with a P-values < 0.05 were interpreted as statistically significant for 2-sided tests. Since multiple comparisons increase the risk of introducing a Type-I error, we applied the sequentially rejective Bonferroni correction (Holm’s correction) to control for this type of error in Tables p-value must be divided by the number of tests run in parallel, resulting in an adjusted level of statistical significance. The corrected p-values for Holm’s correction are reported. For multivariate analysis, Holm’s correction is also applied on p-values of interest obtained by the models.All analyses were performed using SAS software  version 9.3. n = 188). The average patient age was 67.9 years old. Baseline characteristics at inclusion were similar between groups, except for PSA level, which was much lower in the patient group as anticipated due to treatment  and 364/832 eligible controls (43.8%) Fig. . The conp = 1 . For global health status/QOL, emotional functioning, cognitive functioning, fatigue and insomnia, multivariate analysis confirmed the absence of difference shown in univariate analysis with a reduced level of statistical significance using Holm’s correction, with respectively p = 1, p = 1, p = 0.91, p = 1, p = 1, p = 0.29, p = 0.23 for global health status/QOL, emotional functioning, cognitive functioning, fatigue and insomnia, social functioning and pain.Estimation of confounding factors in the multivariate regression model could only be performed for QLQ-C30 summary score, global health status/QOL, emotional functioning, cognitive functioning, social functioning, fatigue, pain and insomnia, for which enough data were collected. Multivariate analysis of QLQ-C30 summary score was conducted on 540 participants using the following variables: age, group (patient vs. control), type of lodging, and presence of a chronic illness. No significant difference of QLQ-C30 summary score was observed between groups  (Table p = 1).Responses to the IPSS questionnaire showed no significant difference between patients and controls for urinary symptoms: the median score was 4 2–8] for patients vs 3 [1–7] for controls, with the majority of subjects in each group classified as suffering from mild urinary symptoms , but a significantly higher incontinence score (IS) in patients . Age adjustment confirmed these results. Frequency of diurnal and nocturnal urination did not differ between groups (p = 1 for both). The majority of subjects in both groups reported frequency of urination between 1 and 6 times per day (58.4% for patients vs. 66.3% controls), with only 12.3% patients and 10.7% controls reporting a frequency ≥ 9 times per day. Similarly, for night frequency, patients and controls mostly reported 1 voiding per night (51.9% vs. 50.5% respectively). Only 4 questions about bladder weakness  showed differences between patients and controls in terms of level of bother experienced.The ICIQ-MLUTS questionnaire showed no difference in voiding score (VS) between patients and controls  in erectile dysfunction between groups with 65.5% of patients having severe erectile dysfunction compared to 32% of controls. Only 11.3% patients were free of dysfunction versus 34.3% of controls. Adjustment for age did not affect the significance of the results.In contrast, the IIEF-6 questionnaire revealed a significant difference (p = 1).The HADS questionnaire showed no difference in the number of participants with probable anxiety and/or depression between groups. Median HADS total score was 8  for patients versus 9  for controls, thus 80.8% patients and 85.6% controls showed absence of anxio-depressive symptoms (n = 39) in AS, 50.5% (n = 187) with a RP alone, 14.6% (n = 54) with EBRT, brachytherapy, HIFU or ADT and 24.3% (n = 90) with CC.QLQC30, IPSS, IIEF-6, HADS and ICIQ-MLUTS scores were analyzed in 370 out of 376 patients  according to the different treatments: 10.5%  between treatments and no potential confounder was highlighted. The Bonferonni-post-hoc-analysis (threshold p <  0.0083) showed significant differences between RP and EBRT or brachytherapy or HIFU or ADT for VS score (p = 0.0009) and IS score (p ≤ 0.0001), whereby VS and IS scores were lowest for patients treated with RP and RT, respectively. IS score was significantly different between AS and RP (p = 0.0013).No significant difference was highlighted for QLQC30 scores . Multivariate analysis was not performed due to insufficient patients with no dysfunction.Erectile dysfunction differed between groups, with severe erectile dysfunction for 33.3, 80.8, 64.8 and 72.2% respectively for AS, RP, EBRT or brachytherapy or HIFU or ADT and CC. The analysis with the 5 classes of erectile dysfunction could not be tested, but when grouping into 3 classes , the Bonferroni-Holm corrected Three clinical trials, have shown equivalent OS between EBRT, RP and AS in low-risk prostate cancer subjects –18. The Our study was particularly adapted to assess the impact of natural aging, diagnosis and treatment on QoL at 3 years after diagnosis. For 376 patients and 188 age-matched controls adjusted for socio-demographic confounding variables, QoL was similar between patients and controls, with a very high QoL and few reported symptoms. Most QoL items were equivalent between groups, except worse social functioning in patients compared to controls, probably linked to side-effects. However, anxiety and depression were not different between patients and controls.Because QoL is affected by various socio-demographic factors , its evaPrevious studies using the QLQ-C30 questionnaire for PCa reported a score of approximately 70 (out of 100) for global QoL in a Finnish and a German population  and 80 iThere was heterogeneity in patients’ characteristics as our study was not randomized. Patients undergoing radiotherapy are usually older, have more co-morbidities and a more aggressive disease . When deIncontinence, bowel dysfunction and erectile dysfunction were the main consequences of treatment. Treatment-related incontinence and erectile dysfunctions appear in the first years of treatment and persist over time with a severity that varies according to treatment . In our In a previous study, long-term change in urinary incontinence was worse for patients treated with RP compared to brachytherapy, while long-term change in urinary irritation/obstruction was worse for patients treated with EBRT or brachytherapy . Two othOur study has several limitations. It is not a prospective study, so urinary and erectile dysfunction and QoL data at baseline are missing. Since assessment was performed 3 years after diagnosis, it could be possible that QoL may have been much reduced within the first 2 years. The social-professional questionnaire was developed for testis patients usually younger and in employment, but provided necessary information for use in the statistical models as well as insights into the implication of diagnosis on working prospects . BecauseOur study comparing health-related quality of life at 3 years after diagnosis suggests that, for PCa patients below 75 years old, the diagnosis of prostate cancer has only a marginal impact on the quality of life and on symptoms, which is an additional argument in favor of PCa screening. Conversely, our data support the hypothesis that the choice of the therapeutic option could affect social functioning due to the potential occurrence of long-term side effects.Additional file 1: Table S1. Profile of subjects from the EPICAP cohort contacted and included in this study.


In Japan, 55.5% of breast cancer survivors (BCSs) are of working age, so various perspectives regarding return to work (RTW) after cancer diagnosis need to be considered. Therefore, this study aimed to clarify the risk factors for resignation and taking sick leave (SL) among BCSs in continued employment at the time of diagnosis.A web-based retrospective cross-sectional survey was conducted on BCSs using data from a 2018 Japanese national research project (Endo-Han) commissioned by the Ministry of Health, Labour and Welfare of Japan. The subjects were women aged 18–69 years who had been diagnosed with breast cancer for the first time at least 1 year previously. The risk factors for resignation and taking SL after breast cancer diagnosis, including age at diagnosis, education level, cancer stage, surgery, chemotherapy, radiotherapy, employment status, and occupational type, were then analyzed using a logistic regression model.In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of the multivariable analysis indicated that lower education level , taking SL , and younger age at diagnosis  were predictors of resignation. Of 229 patients who continued working, SL was taken by 72 (31.4%). In addition, undergoing surgery was found to be a predictor of taking SL .In total, 40 (14.9%) of 269 BCSs quit their jobs at least 1 year after being diagnosed with breast cancer. The results of this study indicated that younger age, lower education level, and taking SL were predictors of resignation after breast cancer diagnosis.The online version contains supplementary material available at 10.1186/s12889-021-10168-2. The number of breast cancer survivors (BCSs), along with their 5-year survival rates, continue to rise steadily in Japan because of early detection and advances in treatment . As breaMaintaining employment after breast cancer diagnosis remains an important issue for not only BCSs and their families, but also employers and society . PreviouMoreover, predictors of work resignation (quitting work) among BCSs include contract or part-time work, with these types of workers demonstrating higher odds of resignation compared with regular and full-time workers . HoweverGiven this background, the objective of this study was to clarify the predictors of resignation and SL among BCSs in continued employment. Clarifying these predictors could be expected to aid health care providers in supporting CSs who continue to work, and to provide evidence that assists physicians, health care staff, and employers in establishing and improving work support systems for BCSs .www.macromill.com/global/index.html). The reward for answering was in the form of points according to the number of questions answered; these points could then be redeemed as cash or exchanged for items.A web-based retrospective cross-sectional survey was conducted on BCSs using data from a 2018 Japanese national research project (Endo-Han) commissioned by the Ministry of Health, Labour and Welfare (MHLW) of Japan. The project developed a questionnaire asking for information about the following factors: age at time of diagnosis; education level; cancer stage; treatment, including surgery, cancer chemotherapy, and radiotherapy; employment status and type (permanent vs. non-permanent work); occupational type (office worker vs. non-office worker); and history of SL use and resignation. Women aged 18–69 years who had been diagnosed with breast cancer for the first time at least 1 year previously were eligible for participation. On January 17–18, 2018, an online questionnaire (in Japanese) was sent via e-mail to 4968 BCSs (age range: 18–69 years) who had registered with the commercial cancer panel Macromill (n = 138), were not working at the time of breast cancer diagnosis (n = 45), had missing data (n = 2), had a history of cancer other than breast cancer (n = 28), or provided unclear answers regarding SL (n = 33) were excluded  , educational attainment ; cancer stage ; surgery (yes/no); cancer chemotherapy (yes/no); radiotherapy (yes/no); employment status ; occupation type (office work vs. non-office work); and SL (yes/no). The dependent variable was continued employment vs. resignation. Multiple logistic regression analysis including all variables was performed to analyze the risk factors for resignation.p < 0.05. The need for informed consent was waived in line with ethical guidelines in medical and health research involving human subjects in Japan ); age: ≥47 years (n = 126 [46.8%]). Mean duration from breast cancer diagnosis to the date of the survey was 55.9 months (approximately 4.5 years). In addition, 73 BCSs (27.1%) had a higher education level, and 163 (60.6%) had early-stage cancer. Regarding treatment methods, 250 (92.9%), 199 (74.0%), and 174 (64.7%) BCSs had experienced surgery, cancer chemotherapy, and radiotherapy, respectively. Regarding occupation type, 117 (43.5%) and 160 (59.5%) BCSs were permanent and desk workers, respectively, and 95 (35.3%) had taken SL.Of the 269 BCSs analyzed, 40 14.9%) resigned from their jobs after being diagnosed with cancer (Table 4.9% resip = 0.020), taking SL , and age ≥ 47 years .As shown in Table p = 0.049), as shown in Table Of 229 BCSs who had not resigned (at 1 year after diagnosis), 72 31.3%) took SL because of cancer treatment (Table 1.3% tookn = 105) that investigated work-related as opposed to clinical factors , this is the first study to investigate predictors of job resignation and SL among BCSs in Japan. We found that 14.9% of the BCSs in this study quit their jobs at least 1 year after being diagnosed with breast cancer. In addition, the post-cancer diagnosis resignation rate differed significantly according to education level, cancer stage, and occupational type. A systematic review reported that CSs were more likely to be unemployed than were healthy controls  , 23. In Second, patients with lower compared with higher educational attainment were found to be at higher risk for resignation. This finding is consistent with previous studies of non-Asian populations , 25–28. Third, our results indicated that the risk of resignation was substantially higher among BCSs who took SL after breast cancer diagnosis than among those who did not. These findings are consistent with previous studies that showed a correlation between length of SL and RTW, with longer SL making RTW and continued employment more difficult , 40. ConRegarding predictors of taking SL, our findings indicated that BCSs who had undergone surgery took SL more frequently than those who had undergone nonsurgical interventions. The distinction between BCSs who undergo surgery and those who do not suggests a relation to cancer stage (early or advanced) because almost all BCSs undergo surgery, except for those with stage IV cancer, in which distant metastasis is apparent. Previous studies have reported that breast cancer surgery is associated with SL lasting 1 month or longer , 43, andThis study did have some limitations. First, recall bias is possible given the nature of the self-report questionnaire design. In particular, as cognitive function may be adversely affected by some forms of treatment, some of the respondents may have been unable to remember when they had been diagnosed with breast cancer or to report how their work had changed after diagnosis. Second, this study was affected by survivorship bias, a form of selection bias, as BCSs who died before completing the questionnaire were excluded. Because BCSs who had been diagnosed with breast cancer within 1 year prior to participation in this study were excluded, we speculate that the resignation rate among BCSs was underestimated because of the death of patients who had left their jobs soon after diagnosis, especially in cases of advanced-stage disease. In addition, younger patients may have felt more comfortable than older patients given the online delivery and design of the survey. Third, SL systems depend on their company rules, so it might be difficult to discuss the risk factors of resignation more strictly. However, as the number of days of annual paid leave is stipulated by the Labor Standards Act , and theAs a future task, while we provided little clinical implications based on the findings of this research, a prospective cohort study (such as an RTW intervention study) involving working BCSs in Japan is needed to clarify the association between clinical factors (symptoms) and work-related factors among BCSs.This study investigated the risk factors for resignation and taking SL after breast cancer diagnosis in Japan. The results indicated that 14.9% of the women diagnosed with BC from the January 17–18, 2018 registry and who were employed at the time of diagnosis quit their job at least 1 year after diagnosis. Younger age at breast cancer diagnosis, a lower education level, and taking SL were identified as predictors of resignation after breast cancer diagnosis, while surgery was associated with the highest risk of taking SL.Additional file 1. A working condition questionnaire for breast cancer survivors


Giant cell arteritis (GCA) is frequently associated with aortic involvement that is likely to cause life-threatening structural complications . Few studies have investigated the occurrence of these complications, and no predictive factor has been identified so far. The aim of this study was to investigate factors associated with the risk of aortic complications in a cohort of GCA aortitis.Data of all patients managed with aortitis (CT or 18 FDG PET) at the diagnosis of GCA in five hospitals from May 1998 and April 2019 were retrospectively collected. Clinical features were compared according to the presence of aortitis symptoms. The predictive factors of occurrence or aggravation of aortic structural abnormalities were investigated.p = 0.0003). In multivariate analysis the presence of aortitis symptoms at diagnosis  and GCA relapse  were factors associated with the occurrence of aortic complications.One hundred and seventy-one patients with GCA aortitis were included; 55 patients (32%) had symptoms of aortitis  at diagnosis. The median follow-up was 38 months. Aortic complications occurred after a median time of 32 months. There were 19 new aortic aneurysms or complications of aneurysm and 5 dissections. Survival without aortic complication was significantly different between the symptomatic and non-symptomatic groups (Log rank, In this study, the presence of aortitis symptoms at the diagnosis of GCA aortitis and GCA relapse were independent predictive factors of occurrence of aortic complications during follow-up. Giant cell arteritis (GCA) is the most frequent systemic vasculitis, in which aortitis is present at diagnosis in 40 to 65% of cases , 2. The There are few data on the prognostic value of aortic involvement in GCA. Overall mortality does not appear to be increased , 11. In To date, there are no clear data on the link between clinical presentation of aortitis, at the time of diagnosis of GCA, and the prognosis of the disease. The aim of this study was to evaluate clinical presentation and outcome of GCA-related aortitis.This study included patients diagnosed with GCA between May 1998 and April 2019 from 5 hospitals in western France. Data were collected from medical records. Each patient had to meet at least three American College of Rheumatology criteria for the diagnosis of GCA ; or be oSymptomatic aortitis was defined by the presence 1 month before or at GCA diagnosis of one or more of the following signs: recent, less 2 months, occurrence of chest, dorsal, lumbar, or abdominal pain; or unknown aortic insufficiency with recent dyspnea highlighted at aortitis diagnosis. This signs were unexplained by any other cause than aortitis .This study have received ethics board approval by GNEDS (Groupe Nantais d’Ethique et de Soins) the local ethics committee of the University Hospital of Nantes (20200219). Each patient included in this study received written information, and no patient objected to this study.Aortic complication was defined by the occurrence, at least 1 month after initial imaging of the aorta, of a new aortic structural abnormality , or the need for aortic surgery in response to a threatening structural abnormality .Peripheral vascular event was defined by the occurrence, at least 1 month after initial imaging, of one of the following complication: limb ischemia, mesenteric or renal ischemia, myocardial ischemia, or ischemic stroke.GCA relapse was defined by the concomitant reappearance of GCA-related clinical manifestations and a biological inflammatory syndrome (CRP ≥ 15 mg/l), or the reappearance of a biological inflammatory syndrome with inflammatory arterial parietal changes on CT, MRI or PET –20.Patients with non-symptomatic aortitis (noS-Ao) at diagnosis were compared to patients with symptomatic aortitis at diagnosis (S-Ao).Only radiographically monitored patients were included in the multivariate study and survival analysis.t test. Frequency comparisons were made by a chi-squared test or the Fisher test according to the statistical headcount. Prognostic factors associated with aortic complication were evaluated with Cox models. Hazard ratios (HR) with their 95%CI has been estimated as association measures. Variables with p < 0.05 in univariate model and all the variables already known to be confounding factors were candidate variables for multivariate model. Survival curves were estimated with their 95% confidence interval (95%CI) using Kaplan-Maier estimators, and Log rank tests were performed to compare aortic complication free survival between groups.Qualitative values were expressed in terms of numbers and percentages. The mean comparisons were made using p = 0.009), 6 (10.9%) in S-Ao, and 4 (3.4%) in noS-Ao (p = 0.08).This study included 171 cases of GCA with aortitis at diagnosis, whose characteristics are described in Table Aortitis was symptomatic in 55 cases (32%), including 51% chest pain, 31% abdominal pain, 16% back pain, and 35% had previously unknown aortic insufficiency with recent dyspnea.Ten patients (5.8%) had undergone aortic surgery for an inaugural complication: 5 Stanford-A aortic dissections (1 patient died), and 5 ascending thoracic aorta aneurysms .n = 31) of cases (12.7% in S-Ao and 20.7% in noS-Ao (p = 0.20)): methotrexate in 23 cases, tocilizumab in 3 cases, azathioprine in 3 cases, and cyclophosphamide in 2 cases.Immunosuppressive treatment was introduced in 18.1% (p = 0.77).At least one control imaging  was performed for 98 patients: 44 (80%) of S-Ao patients and 54 (52%) of noS-Ao patients. For patients who had a control imaging during follow-up, mean duration between initial and last imaging was 35.6 months (± 34.7), mean follow-up time was 34.4 months (± 30.8) for S-Ao patients and 36.5 months (± 37.9) for noS-Ao patients (p < 0.01); these complications do not include aortic aneurysms, dissections or surgeries that occurred at diagnosis or in the month following the diagnosis of GCA. There were 15 new aortic aneurysms, 4 critical increase size of a pre-existing aneurysm requiring surgery, and 4 aortic dissections: 3 (5.5%) in S-Ao and 1 (0.9%) in noS-Ao (p = 0.06).Twenty-three aortic complications occurred during follow-up (23.5% of patients with control imaging): 15 in S-Ao patients (34.1% with control imaging) and 8 in noS-Ao patients (14.8% with control imaging)  and GCA relapse  were independent factors of aortic complication.Multivariate cox model Table  showed tp = 0.0003)  Fig. .Fig. 1Sp = 0.18); 8 (15%) S-Ao and 21 (18%) noS-Ao patients developed subsequent peripheral vascular event (p = 0.72). Eighteen patients died during follow-up . Causes of death recorded were 1 dissection of the thoracic aorta, 1 rupture of an abdominal aortic aneurysm, 5 cardiovascular causes, 3 infections, 1 cancer, and 1 severe hemorrhage.Nineteen (35%) S-Ao and 53 (46%) noS-Ao patients had a GCA relapse  than asymptomatic patients, suggesting a potential additional effect leading to severe aortic involvement. In accordance to the literature, the aorta was mostly affected in its thoracic segment, especially the ascending thoracic aorta , 2. AortIn our experience, patients with non-symptomatic aortitis received more frequently Methylprednisolone pulses. This is in part due to a higher frequency of ocular involvement in these patients. The use of immunosuppressive treatment during follow-up remained infrequent  and mainly used for severe or resistant forms.In case of aortitis, control imaging should be used to assess evolution and detect structural complications. The lack of systematic monitoring probably leads to an underestimation of the actual number of aortic complications. In the presence of aortitis, imaging at 1 and 2 years from the diagnosis may be considered to assess wall inflammation and screen for aortic aneurysms; later imaging can be discussed in case of multiple relapses or corticosteroid dependence.During GCA, possible predictive factors of aortic complication  have already been suggested: coronary artery disease and hypercholesterolemia , 12, artIn this study, 23.5% of patients (14.8% of noS-Ao patients and 34.1% of S-Ao patients) developed an aortic complication after a median delay of 27 months, which is quite similar to the 2.5 years found in the historical study by Evans et al. [This study presents an original concept with the search for clinical signs of aortitis at GCA diagnosis. If these results are confirmed, imaging could help identify patients with more aggressive aortitis.Our study has several limitations: with the potential data capture errors and missing data that are inherently an issue with all retrospective data collection and short median follow-up. Although the initial dose of corticosteroid therapy was the same in both groups, tapering schedules were not standardized, and the use of immunosuppressive therapy was not standardized. Moreover, for most patients, control modalities and blood pressure objectives were not clearly indicated. Only 18.1% of the cohort were treated with additional immunosuppression despite recent EULAR recommendations  since thIn addition, clinical signs associated with symptomatic aortitis are non-specific: pain or dyspnea is very frequent in elderly population; however in this study, symptomatic aortitis was retained after exclusion of musculoskeletal degenerative disease and atherosclerotic or other aortic disease that could explain these symptoms.Several aortic CT scans performed were not synchronized to the heart rate  and some had no late arterial phase to evaluate aortic parietal contrast; follow-up imaging was not systematic and was performed at widely varying times.If these data are confirmed in prospective studies, a more intensive initial treatment for symptomatic aortitis at diagnosis—with initial corticosteroid therapy combined with immunosuppressive therapy—could be evaluated.The management of cardiovascular risk factors is also fundamental, including blood pressure monitoring with self-measures, a strict goal for LDL cholesterol level, smoking cessation, and regular physical activity.Aortitis in GCA may lead to severe complications like aneurysm or dissection. Patients who have symptomatic aortitis, mainly chest and abdominal pain, at the time of diagnosis of GCA, could represent a distinct sub-group of aortitis with more aortic aneurysm or dissection during follow-up than patients with non-symptomatic aortitis. Prospective studies are needed to confirm our results. In order to take better care of these patients, recommendations on the frequency and modalities of aortic imaging remain to be defined.


Percutaneous endoscopic decompression (PED) is considered a minimally invasive and safe procedure in lumbar degenerative disease. Few authors report the success of PED for thoracic spinal stenosis (TSS) with thoracic myelopathy. The objective of this study was to compare the outcome of PED versus posterior decompressive laminectomy (PDL) for TSS.n = 16) and PDL(n = 14) group. Preoperative demographic characteristics and perioperative outcomes were reviewed. Pre- and postoperative neurological status was evaluated using the modified Japanese Orthopaedic Association (mJOA) score and the recovery rate (RR).We retrospectively reviewed 30 consecutive patients who underwent surgery for single-level TSS from January 1, 2015 to May 1, 2019.These patients were divided into PED (P > 0.05), while the PED brought advantages in operative time(m) , blood loss (mL) ,drainage volume(mL) , and hospital stay (d) .The patients’ mean age was 57.3 years (27–76) in PED group and 58.8 years (34–77) in PDL group. No statistical difference was found between two groups with regards to neurological status at pre-operative and final follow-up. The RR in PED group achieved the same improvement as PDL group (87.5% vs 85.7%, Both PED and PDL showed favorable outcome in the treatment of TSS. Besides, PED had advantages in reducing traumatization. In terms of perioperative quality of life, PED could be an efficient supplement to traditional posterior decompressive laminectomy in patients with TSS. Thoracic spinal stenosis (TSS) with thoracic myelopathy. Usually caused by thoracic ossification of the posterior longitudinal ligament or ligamentum flavum, and intervertebral disc herniation, is a reduction of the spinal canal with associated compression of the thoracic spinal cord . DiagnosThe major studies show that conservative therapy is not effective in TSS with myelopathy to prevent the sequelae of spinal cord compression. Traditional open spinal decompression, involving spinous process and paraspinal muscle dissection, en bloc resection of lamina and removal of the intervertebral disc herniation and hyperplastic ligament, is the prevailing therapy , 4. AlthThis study was approved by the Ethics Committee of our hospital, written informed consent was obtained. From January 1, 2015 and May 1, 2019, 30 consecutive patients underwent surgery for single-level TSS, including 16 patients who underwent PED and 14 patients who underwent PDL. Inclusion criteria: patients with single-segment TSS confirmed by MRI and CT. Exclusion criteria: Combined with lumbar or cervical degenerative disease. Preoperative demographic characteristics, perioperative outcomes and neurological status were recorded. The full percutaneous endoscopic spine system, bipolar radiofrequency system, and endoscopic instruments  were used in PED.For PED group, the surgical procedure was performed below (Based on T10–11 Segment of OLF):After positioning in the prone position, local anesthesia was used to allow for communication between the surgeon and patient during the procedure. The entry point was 3–5 cm from the midline. After anesthesia the skin, a spinal needle was introduced Fig. . The neeFor PDL group, the surgical procedure was performed as described below (en bloc decompression):The surgical method and steps were consistent with that reported in the literature . To reduPreoperative demographic characteristics and perioperative outcomes were compared. Neurological status were evaluated using the mJOA score. Neurological recovery was assessed based on the RR. The RR = (postoperative - preoperative mJOA score)/(11-preoperative mJOA score) × 100. A score of 0–24% was poor; 25–49%, fair; 50–74%, good; and 75–100%, excellent [P < 0.05 was considered significant.Statistical assessments were analyzed using the SPSS 21 program . The independent samples t-test and chi-squared test were used to evaluate preoperative demographic characteristics and perioperative outcomes, and repeated-measures analysis of variance was used to evaluate mJOA between the two groups. p < 0.05), blood loss (mL) ,drainage volume (mL) , hospital stay (days) .We kept in contact with all of the 30 patients (16 in PED group and 14 in PDL group) throughout the follow-up. Preoperative demographic characteristics were similar in the two groups as shown in Table P < 0.05). In the preoperative stage, the mean mJOA scores were similar between the 2 groups . The mean mJOA scores of the PED group improved to 9.5 ± 1.3 at the last follow-up (P < 0.05). The mJOA scores also improved significantly in the PDL group to 9.1 ± 1.0 at the last follow-up (P < 0.05). Moreover, there were no intergroup differences at any follow-up time point between groups (P > 0.05). Good-to-excellent rate was no differences at the final follow-up.Statistically improvements in clinical outcomes before surgery to 3, 6, and 12 months after surgery were estimated by the mJOA score and RR  treating TSS also has been reported by Baba . AlthougThe postoperative outcomes showed that preoperative symptoms were relieved and the decompression was completed without severe complications Figs.  and 5. TNeurological deterioration is a serious complication for TSS . Some auOne of the most common complications of the traditional open spinal decompression is CSF leakage . AlthougWe do not recommend that beginners perform PED independently for the flat learning curve. However, with proper diagnosis, precise indication, and good training, experienced skilled surgeons can use the PED to treat TSS. The primary limitations of the retrospective study are the relatively small number of patients and following time.Both PED and PDL showed favorable outcomes for the treatment of single-level TSS. In terms of perioperative quality of life, PED under local anesthesia can be considered as the effective alternatives to traditional open spinal decompression. However, prospective, randomized, controlled trials with a larger sample size and longer follow-up are required in the future.


To explore the relationship between elevated serum C-reactive protein (CRP) level and postoperative delirium (POD).  206 patients scheduled to receive cervical or lumbar vertebra surgery under general anesthesia for more than 2 hours in a single medical center were observed and analyzed. Patients' serum CRP, delirious status (using the confusion assessment method (CAM)), and delirious score ) were examined before surgery and 1-2 days after surgery. The association of a serum CRP elevation value from before to after surgery (D-CRP) with delirium occurrence within 2 days after surgery was assessed with a binary logistic regression model, while the association of D-CRP with the postoperative delirious score was assessed with a linear regression model. The effect of D-CRP on predicting delirium occurrence was evaluated with the area under the receiver operating characteristic (ROC) curve (AUC). β = 0.014, 95%CI = 0.006, 0.023). AUC of ROC was 0.711 (P = 0.014), suggesting that D-CRP had moderate efficacy on predicting postoperative delirium occurrence (P < 0.05).  D-CRP was significantly positively associated with postoperative delirium occurrence , and D-CRP was also significantly linearly associated with the postoperative delirious score ( Elevated serum CRP after surgery may be a risk factor for and a predictor of postoperative delirium. Postoperative delirium (POD) is a common complication of the central nerve system after surgical operations in elderly patients, usually characterized by a fluctuating course of altered consciousness, disordered thinking, and inattention . The incIt is well established that surgeries, especially major surgeries, are associated with significant system inflammation. The response of the brain to inflammation, including activation of microglia and neuronal apoptosis, may lead to synaptic and neurochemical disturbances . It has Elevated serum C-reactive protein (CRP) level is widely used to indicate acute systemic inflammation in clinical practices –9. IncreThis study was a prospective observational investigation conducted from June to October in 2014 in Zhongda Hospital of Southeast University, Nanjing, China. Zhongda Hospital is a large general hospital with the top rank in China and admits approximately 18000 patients for surgeries every year. The eligible participants were adult cervical and/or lumbar inpatients if they (1) were scheduled to receive open surgeries , such as transforaminal lumbar interbody fusion (TLIF), spinal canal enlargement and decompression, anterior or posterior cervical decompression, or posterior approach of scoliosis with internal fixation and fusion; (2) had American Society of Anesthesiologists (ASA) classification not more than III; (3) had no history of neuropsychiatric disease or dementia and had no recent central neurological damage or psychiatric medication within 3 months; (4) had no cognitive impairment, which was assessed in this study using the Chinese Mini-Mental State Examination (MMSE), which includes 19 independent items with a score of 30 in total   were monitored. Midazolam 0.03-0.05 mg/kg , sufentanil 0.2-0.3 μg/kg, propofol 1-1.2 mg/kg, and rocuronium bromide 0.6-0.8 mg/kg were injected intravenously in a sequential manner for general anesthesia induction. Endotracheal intubation was performed after adequate muscle relaxation, followed by mechanical ventilation . Anesthesia was maintained with 1% sevoflurane inhalation and intravenous infusion of propofol 1.5-2.0 mg/kg/h and remifentanil 1-5 μg/kg/h to keep circulation stability. For those who received dexmedetomidine infusion during anesthesia induction, dexmedetomidine infusions were continued at the rate of 0.1-0.2 μg/kg/h during anesthesia maintenance. Bolus cisatracurium 10 mg was applied intermittently when necessary to keep muscle relaxation. In case of hypotension over 20% of the patient's baseline blood pressure, a bolus dose of dopamine 2-3 mg, or bolus atropine 0.25 mg for bradycardia under 50 bpm, was applied for rescue. Infusion speed and infusion type were adjusted referring to CVP and arterial blood gas to maintain the patients' CVP similar to their preoperative baseline values and hemoglobin (HB) above 90 g/L.All patients received no preoperative medication. After entering the operation room, peripheral and central venous access was established and the invasive blood pressure (IBP), electrocardiograph (ECG), central venous pressure (CVP), and pulse oxygen saturation , an instrument for qualitatively measuring the status of delirium , and theCAM comprises four domains: (a) acute onset and fluctuating course, (b) inattention, (c) disorganized thinking, and (d) change of consciousness level . A patient would be regarded as having delirium at the time point, if he/she responded positive to (a), (b), and (c)(/d) at each time of assessment. Otherwise, the patient was regarded as having no delirium at the time point. Subsequently, for analysis, a participant was classified as “yes” to POD if he/she was assessed having POD at any of the 2 postoperative time points. Otherwise, he/she was recorded as “no” to POD in analysis.MDAS consists of 10 questions about the patients' consciousness level, disorientation, short-term memory impairment, digital span test, disability to maintain attention, disorganized thinking, perception disturbance, delusion, psychomotor activity change, and sleep-wake cycle disturbance. The research member interviewed each patient to assess the potential delirium status and recorded their status as normal (score = 0), mild (score = 1), moderate (score = 2), or severe (score = 3) based on the patient's response to each question. Thus, the potential score sum of MDAS was maximally 30 for a patient at each time point. For analysis, the mean value of scores assessed at two postoperative time points was used for each participant in this study.The independent variable of this study was the difference in values of serum CRP between before and after surgery (D-CRP), which was used as the continuous variable. Preoperative and postoperative blood samples of all patients were obtained 1 or 2 days before surgery and 1 day after surgery, respectively. The blood samples were centrifugated for serum and stored in a -80°C refrigerator for further measurement. Serum CRP levels were measured by velocity ratio turbidity .Some classical potential confounders have been identified for POD . Therefot-test was used to compare the differences between continuous measures (expressed as mean ± SD). The binary logistic regression model was applied to examine the relationship between D-CRP and postoperative delirium occurrence. The linear regression model was introduced to investigate the relationship between D-CRP and postoperative delirium score. In these two models, the potential confounding factors  were adjusted. The area under the ROC curve (AUC) was used to evaluate the predictive effect of D-CRP on POD. P < 0.05 was regarded as statistically significant. The software SPSS 22.0  and Prism 7  were applied to analyze all the data in this study.Chi-square analysis was used to compare the differences between categorical variables, and Students' P = 0.02). The mean value of the MDAS score was 6.20 ± 3.16 and 0.08 ± 0.39, respectively (P < 0.001). There was a significant difference in age, ASA classification, surgery types, mean MDAS score, and postoperative CRP value between those patients having and not having postoperative delirium. However, no difference was observed in gender, BMI, blood transfusion, anesthesia time, extubation time, and postoperative HB between the two groups of participants.Based on ROC curve analysis, the AUC was 0.71  for D-CRP to predict POD occurrence among these study patients, suggesting that D-CRP had a moderate predictive effect on postoperative delirium occurrence among adult cervical/lumbar inpatients .POD is one of the key manifestations of perioperative neurocognitive disorders (PND) . It is aCRP is a positive acute-phase protein of inflammation and an objective and reliable indicator of inflammatory response and tissue damage . It is pThere are few reports on the relationship between CRP and postoperative delirium in China. The only published research found online on this issue in the Chinese population reported the predictive effect of high preoperative CRP level on POD . WorldwiCAM is an internationally recognized method for judging a delirium state, with a sensitivity of 94%-100% and a specificity of 90%-95% . MDAS isThe purpose of this study was to explore the relationship between the perioperative increase in CRP and delirium occurrence after operation. In order to reduce the heterogeneity of research objects from a clinical context, a single type of anesthesia and operation was applied in the study. Further, to reduce the influence of possible confounding factors, multivariate analysis models were applied to adjust the factors, such as age, gender, BMI, blood transfusion, and ASA grade. Both logistic and linear regression analyses showed that the increase in CRP after surgery was significantly related to the occurrence of delirium. Moreover, ROC curve analysis showed that the increment amplitude of CRP had a moderate predictive effect on the occurrence of postoperative delirium, which suggested that the increase in CRP after anesthesia and surgery was a risk factor for postoperative delirium occurrence.The incidence of postoperative delirium (5.8%) among participants in this study was lower than that reported from previous studies, whereas POD incidence ranged from 35% to 65% for cardiac surgery or total hip replacement and 9%-15% for elective orthopedic surgeries . This miThere are some limitations in this study. First, POD was assessed once daily within day 1 and day 2 after surgery in our study, so such a short observation time might imply that potential POD cases might not be identified if they occurred at different time points in days 1-2 or occurred in days 3-7 after surgery, although evidence has suggested that most POD occurs within the first two postoperative days and POD assessment once daily was acceptable –22. ThisIn conclusion, our study suggests that elevated serum level of CRP alone is a risk factor for and predicts postoperative delirium in patients receiving cervical-lumbar surgeries.


Serum neutrophil gelatinase-associated lipocalin (NGAL) could be used as a predictive marker of acute kidney injury (AKI) in patients with return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) who are managed with targeted temperature management (TTM). However, the NGAL measurement timepoints vary from immediately after ROSC to several days later. The primary objective of this study was to determine an association between AKI and NGAL, both immediately (ROSC-NGAL) and 3 h after ROSC (3 h-NGAL), in OHCA patients with TTM. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge.This prospective observational study was conducted between January 2016 and December 2018 and enrolled adult OHCA patients (≥18 years) with TTM after ROSC. The serum NGAL level was measured both immediately and 3 h after ROSC. Univariate and multivariate analyses were performed to identify the associations between AKI, poor neurologic outcome, and NGAL.p = 0.001). The area under the receiver operating characteristic curve of 3 h-NGAL for AKI was 0.910 (95% CI 0.830–0.960), and a cut-off value of 178 ng/mL was identified. Both ROSC-NGAL and 3 h-NGAL were not significantly associated with poor neurologic outcome on multivariate logistic regression analysis .Among 861 OHCA patients, 89 patients were enrolled. AKI occurred in 48 (55.1%) patients. On multivariate logistic regression analysis, 3 h-NGAL was significantly associated with AKI (odds ratio [OR] 1.022; 95% confidence interval [CI] 1.009–1.035; The serum NGAL concentration measured 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Future research is needed to identify the optimal measurement timepoint to establish NGAL as a predictor of neurologic outcome and to validate the findings of this research. The post-cardiac arrest syndrome (PCAS) develops in cardiac arrest patients after the return of spontaneous circulation (ROSC) and comprises anoxic brain injury, post-cardiac arrest myocardial dysfunction, systemic ischemia–reperfusion response, and persistent precipitating pathology . The iscSeveral reports of the positive association between AKI and NGAL in post-cardiac arrest patients indicate that NGAL could be used as a predictive marker of AKI; however, in those studies, the timepoint of NGAL measurement varied from immediately after ROSC to several days later –15. If tThis study aimed to evaluate the correlation between NGAL and AKI to evaluate the use of NGAL as a predictive marker for AKI in patients with PCAS. The primary objective of this study was to determine an association between AKI and NGAL, both immediately and 3 h after ROSC, in out-of-hospital cardiac arrest (OHCA) patients who underwent targeted temperature management (TTM) after ROSC. The secondary objective was to ascertain the association between NGAL levels in the early post-ROSC phase and the neurologic outcomes at discharge.This prospective observational study was conducted at single tertiary hospital in Seoul, South Korea between January 2016 and December 2018. The target study population comprised all adult OHCA patients (age ≥ 18 years) who underwent TTM after ROSC. Patients with active intracranial bleeding, a do-not-resuscitate order, underlying disease with life expectancy < 6 months, pre-arrest cerebral performance category of 3 or 4, body temperature < 30°  score that comprises five categories: good recovery (CPC 1), moderated disability (CPC 2), severe disability (CPC 3), vegetative state (CPC 4), and brain death or death (CPC 5)  min vs 16.5 [10.5–29.5] min). The epinephrine dose used in CPR was significantly higher in the PNO group. However, there were no significant differences in bystander CPR, time from EMS activation to EMS arrival, and time from EMS activation to first defibrillation.The clinical characteristics were compared according to AKI occurrence and neurological outcome Table . The ROSIntergroup comparison of the ROSC-NGAL and 3 h-NGAL levels in the groups stratified by the neurologic outcome at discharge showed significantly higher levels of NGAL in the PNO group. The percentage of patients who needed continuous renal replacement therapy was significantly higher in the PNO group (23.1% vs 3.6%), whereas a significantly higher percentage of patients in the GNO group underwent coronary angiography  and AKI (−) groups. The results of multivariate logistic regression analysis showed that unwitnessed cardiac arrest  and 3 h-NGAL  were significantly associated with AKI  and the higher dose of epinephrine used during CPR  were significantly associated with poor neurologic outcome , whereas the cut-off value was 178 ng/mL. Therefore, the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for AKI were 83.67 (95% CI 70.3–92.7), 90.00 (95% CI 76.3–97.2), 8.37 (95% CI 3.3–21.4), and 0.18 (95% CI 0.10–0.3), respectively. The AUROC of ROSC-NGAL was 0.698 (95% CI 0.591–0.791), which was significantly lower than that of 3 h-NGAL . In a 2015 study by Geri et al. [p = 0.03). A similar tendency was identified in this study, wherein a comparison of survival at discharge, CPC at discharge, and the 1- and 6-month survival in the AKI (+) and AKI (−) groups showed a significantly higher frequency of poor outcome in the AKI (+) group.AKI is associated with poor clinical outcome in PCAS patients, and the incidence of AKI in PCAS patients ranges from 12 to 80% –7. In a i et al. , Stage 3The appropriate management of AKI, which has an effect on poor prognosis in PCAS patients, requires the prediction and early management of AKI. In the results reported from a study by Choi et al.  in 2020,Human NGAL was originally identified as a novel protein that was isolated from the secondary granules of human neutrophils . Preclinp = 0.02). In a 2017 study, Kaneko et al. [p = 0.084, 3 h-NGAL: OR 0.997; 95% CI 0.992–1.001; p = 0.113). The neuroprognostic value of NGAL measured within 24 h is remains controversial [Research has been actively undertaken on NGAL and clinical outcomes in OHCA patients. In a 2019 study by Lee et al. , the plao et al.  analysedoversial ; therefoThis study had several limitations. First, in patients with missing data for the serum creatinine level, we used the creatinine level on the first day of hospitalisation as the baseline value. Second, the study did not consider the potential effect of the history of concurrent medications and the radiocontrast procedure on renal function, volume status after admission, and the onset of complications. Third, the single-centre study design is another limitation of this study. Forth, number of study patients was low. The frequency of OHCA is extremely low, and this limitation is difficult to avoid due to the nature of the disease. However, this drawback may be circumvented by multicentre research studies. Fourth, a recent study reported the hepatic production of NGAL via the IL-6 level. Therefore, the results of this study should be interpreted with due consideration to conditions that may increase IL-6 as well as the risk of AKI.The serum NGAL concentration measured at 3 h after ROSC is an excellent early predictive marker for AKI in OHCA patients treated with TTM. Further research is needed to identify the optimal timepoint of measurement to establish NGAL as a predictor of the neurologic outcome and to validate the findings of this research.Additional file 1. General and clinical characteristics of study patients according to AKI stages