Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs).This was a retrospective observational study. This study included 67 patients  with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU.Upon admission, the median age was 70  years, and RA duration was 10  years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission.Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU. Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disorder that promotes the production of inflammatory cytokines, which leads to the destruction of joints and systematic complications . ImmunosA previous study reported that the reasons for the ICU admission of RA patients included CVD and serious infection and showed that RA patients have increased one-year mortality compared with the general population . The proRA patients require hospitalization for surgery and various systemic medications owing to joint destruction, flare, or complications and have a high incidence of ICU admission. Thus, this study investigated the prognostic factors for short-term mortality in RA patients after ICU admission.This single-center retrospective study reviewed the medical records of all consecutive patients with RA admitted to the ICU of Kyushu University Hospital for ≥48 h between January 1, 2008, and December 31, 2017. Kyushu University Hospital is a 1275-bed national university teaching hospital located at Fukuoka in the south of Japan. This hospital has a critical and emergency care center for patients with severe disorders and/or multiple traumas, as well as an organ transplant center. Our ICU has 10 beds for critical and emergency care and 10 beds for postsurgical and nosocomial severe patients. To identify patients who require intensive care, we excluded patients who were admitted overnight for postoperative observation and analyzed patients who were admitted for ≥48 h. No RA patients died within 48 h after ICU admission in our study. RA diagnosis was established according to the classification criteria of the American College of Rheumatology , and patThe primary outcomes were the 30-day, 90-day, and 1-year survival rates of all patients included in the study. Information on patient survival was obtained from medical records at our hospital and/or changing hospital after 30 days, 90 days, and 1 year. A total of 67 patients were followed up at 30 and 90 days, but 5 patients were lost to follow-up 1 year after ICU admission because the patients changed hospital or did not return to the hospital.U test. The survival of patients with RA after ICU admission was analyzed according to the Kaplan–Meier method with computation of 95% confidence intervals (CIs). To identify the independent predictors of mortality in patients with RA admitted to ICU, the Cox proportional hazards model was used. The variables for multivariable analysis were selected from the statistically significant variables identified by univariable analysis using the Lasso approach. Statistical difference was defined as P < 0.05 for all comparisons. All data were presented as mean ± standard deviation .Statistical analysis was performed using JMP pro 13.0.0 . Categorical variables in 30-day mortality were compared using Pearson’s chi-squared test, and continuous variables were analyzed by the Mann–Whitney n = 67) who were admitted to the ICU at Kyushu University Hospital between January 1, 2008, and December 31, 2017 (Table P = 0.1680) or csDMARDs (P = 0.4493) immediately prior to ICU admission showed no statistical difference, whereas the use of glucocorticoids (P = 0.0239) was associated with poorer prognosis in nonsurvivors in the 30-day mortality group in a glucocorticoid (conversion of prednisone) dose-dependent manner (P = 0.0095). After ICU admission, patients who were able take csDMARDs and/or glucocorticoid continued with this medication, whereas those who were unable to take anything by mouth were administered a corresponding amount of glucocorticoid without csDMARDs via injection until they could take oral medicine. Treatment with bDMARDs was temporally discontinued during the ICU stay. Most patients, who had been recovered from critical condition and could take orally, has begun taking same amount of DMARDs again. bDMARD contained infliximab, etanercept, and tocilizumab, and csDMARDs were methotrexate, tacrolimus, salazosulfapyridine, bucillamine, mizoribine, iguratimod, and cyclosporine. No patient had been treated with tsDMARDs.This study included 67 consecutive patients with RA (P = 0.0001), including the liver disease (P = 0.0004) and renal disease scores (P = 0.0009), was significantly increased in nonsurvivors compared with survivors.The comorbidities of the RA patients were calculated using updated CCI, which predicts hospital mortality by classifying or weighting comorbidities , 20 (TabP = 0.0029). The duration of ICU stay showed no difference between nonsurvivors and survivors groups, whereas hospitalization was statistically shorter in the 30-day mortality group owing to death within 30 days. The main reason for ICU admission was infection   (Table P = 0.0005) , elevated updated CCI , high APACHE II score , and extended PT-INR  were associated with an increased risk of mortality after ICU admission.Table This study retrospectively analyzed the prognosis of 67 RA patients after ICU admission and identified the predictive factors of mortality. We elucidated that the prognostic factors of mortality for RA patients admitted to ICU included the use of csDMARDs, elevated updated CCI, high APACHE II score, and prolonged PT-INR at ICU admission.Previous studies have examined the risk factors and mortality of RA patients after ICU treatment , 27, 28.RA patients often have several comorbidities, and previous studies have reported the risk factors for ICU admission and mortality, such as pulmonary disorder, renal dysfunction, and hypertension , 13, 15.et. al demonstrated that the DIC and APACHE II scores were independently correlated with survival time [R = − 0.1363, P = 0.2714), suggesting that prolonged PT-INR in combination with the APACHE II score might predict mortality in patients with RA admitted to the ICU.Some studies have reported that the prognostic factors of ICU mortality in patients with RD included high APACHE II and SOFA scores, serious infection, mechanical ventilation, vasopressor, renal replacement therapy, and glucocorticoid dose , 17, 28.val time . AdditioThis study has several limitations. First, clinical data were retrospectively analyzed. Second, this study used a small cohort from a single institution and did not include a control group. However, the characteristics of the patients treated at the ICU vary between different institutions. Our study was able to analyze an RA population with more critical comorbidities and complications because our institution treated patients with more severe disorders, such as organ transplantation, compared with other institutions around this area. Third, we did not analyze the disease activity of all RA patients, and this approach may have affected the interventions and outcomes of the patients. However, it was difficult to identify disease activity because our study included patients with impaired consciousness and/or are immobile.In summary, our study showed that RA patients admitted to the ICU have high 30-day (21%), 90-day (27%), and 1-year (37%) mortality. Comorbidities, such as liver disease and renal failure, increased the risk of mortality, and most patients requiring renal replacement therapy had a fatal outcome. Infectious complications were the highest in the nonsurvivors of the 30-day mortality group. The multivariate analysis revealed that the risk factors for mortality in patients with RA admitted to the ICU are nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and prolonged PT-INR.


We assessed the image quality of endometrial cancer lesions by readout segmentation of long variable echo-trains (RESOLVE) diffusion-weighted imaging (DWI) compared with that by single-shot echo-planar imaging (SS-EPI) DWI, aimed to explore the value of RESOLVE DWI for determining myometrial invasion and clinical stage in endometrial cancer.From April 2017 to March 2018, a total of 30 endometrial cancer patients (mean age 52.8 ± 9.0 years), who had undergone RESOLVE DWI and SS-EPI DWI, were included in the study. The image quality of endometrial carcinoma by two kinds of DWI scanning methods was compared qualitatively and quantitatively. The Spearman rank correlation test was used to assess the correlation of qualitative image quality scores between two readers. The accuracy of two DWI methods in detecting myometrial invasion and staging of endometrial carcinoma was calculated according to postoperative pathological results. The indexes were analyzed including sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV).P < 0.001). Interobserver agreement of depiction was good or excellent in two DWI sequences. Signal to noise ratio and contrast to noise ratio values in RESOLVE DWI group were both higher than those in SS-EPI DWI group (P<0.001). No statistical difference of apparent diffusion coefficient value was observed between two DWI groups (P = 0.261). The specificity, accuracy, PPV, and NPV of estimating myometrial invasion by RESOLVE DWI in three cases  were all higher than those by SS-EPI DWI for endometrial carcinoma. Especially RESOLVE DWI was valuable in judging <50% superficial invasion . No significant difference in accuracy staging was between the two DWI groups (P = 0.125).The qualitative score of RESOLVE DWI group was superior to SS-EPI DWI group in every aspect of five aspects (all RESOLVE DWI can provide higher quality images of endometrial carcinoma than SS-EPI DWI. The high-quality images are helpful for precise assessment of myometrial invasion in endometrial cancer. Endometrial cancer is one of the most common malignant tumor threatening to female health . The incMagnetic resonance imaging (MRI) has been widely accepted for the evaluation of myometrial invasion and extrauterine tumor spread owing to its superior contrast resolution and excellent soft tissue differentiation . HoweverDWI has been used as an adjunct to conventional MRI in the evaluation of endometrial cancer lesions by providing quantitative information about water molecular diffusion, but its disadvantage is leading degradation of image quality . TherefoTherefore, this study aimed to apply RESOLVE DWI to endometrial cancer. The study had two purposes. The primary was to compare the image quality of endometrial cancer lesions with RESOLVE DWI and SS-EPI DWI. The secondary was to evaluate the value of RESOLVE DWI in determining myometrial invasion and clinical stage of endometrial cancer.n = 2); (2) receiving antineoplastic therapy before operation after pelvic MRI examination (n = 2). 30 patients  were finally included in our study  contraindications of MRI examination with claustrophobia and metal objects in the body such as metal stents, cardiac pacemakers, and intrauterine devices . The coil specifications were standard 16-channel phased-array body coil and 32-channel phased-array spinal coil. The scan ranges from the upper margin of the ilium to the symphysis pubis. All patients received MRI examinations in the non-menstrual period. Each patient had a fasting for 6 h before examination and kept the bladder adequately filled.2 and 1000 s/mm2 was completed. The protocol parameters were shown in Table Scan sequences contained turbo spin-echo (TSE) T1WI, TSE T2WI, contrast-enhanced TSE T1WI, RESOLVE DWI, and SS-EPI DWI. TSE T1WI was acquired in axial planes. Fat suppressed TSE T2WI were acquired in three orthogonal planes . Immediately after bolus injection of Gadopentetate Dimeglumine (Gd-DTPA) with a dose of 0.1 mmol/kg , fat-suppressed TSE T1WI were obtained in the axial, sagittal, and coronal planes. All patients underwent SS-EPI and RS-EPI DWI scanning of pelvic cross-section, respectively. Meanwhile, images reconstruction of diffusion sensitive gradient b value 0 s/mmAll the measurements and evaluations were conducted by Siemens 3.0 T Skyra MR work station (version syngo MR D13). The MRI images were reviewed independently by two senior radiologists respectively with 10 years and 12 years of working experience and were blinded to the histopathology reports. Any discrepancies were resolved by consensus. The analytic content was as follows: qualitative and quantitative assessments of image quality, the depth of myometrial invasion, and the preoperative stage.2). These four aspects were geometric distortion, image blurring, ghosting artifacts, and lesion conspicuity [Based on the related literature, the study firstly analyzed the quality of MRI images from four aspects (b 1000 s/mmspicuity . The scospicuity . The sco2). Each index was measured three times for each case, and the average was taken as its final value. SNR was defined by the following formula: SNR = SI (lesion)/SD (background) [2 was obtained on the axial sections. All ROIs were put on the same slice on which the maximum area of the endometrial carcinoma shown. The selected ROIs of SI (lesion) were consistent with that of ADC value measurement in the same patient. CNR was defined by the following relationships: CNR = (SI (lesion) –SI (myometrium))/ SD (background) [0/SI1)/(b1-b0). b1 = 1000s/mm2, b0 = 0 s/mm2. SI1 and SI0 represented the SI of the lesion at a b value of 1000s/mm2 and 0 s/mm2, respectively [The quantitative analysis included the measurement of signal to noise ratio (SNR), contrast to noise ratio (CNR) and ADC. The measurement method on RESOLVE DWI is shown in Fig. kground) . SI (leskground) . SI , presence of cervical stromal invasion, and presence of metastasis within the sampled lymph nodes were confirmed microscopically. The staging standard of endometrial cancer patients was the International Federation of Obstetrics and Gynecology (FIGO) 2009 criteria.P < 0.05. The SNR, CNR, ADC value and qualitative scores of image quality were compared between the RESOLVE DWI and SS-EPI DWI group respectively. The Paired t-test was used for continuous variables (SNR and CNR). The Wilcoxon’s signed-rank method for non-normal Distribution Variables .All statistics were performed using SPSS 25.0. Differences among the data were considered statistically significant at a) was obtained to compare the degree of correlation as follows: little or no relationship if 0 ≤ ra < 0.2, fair if 0.2 ≤ ra < 0.4, moderate if 0.4 ≤ ra < 0.6, good if 0.6 ≤ ra < 0.8, and excellent if 0.8 ≤ ra. The accuracy of myometrial invasion and preoperative staging of endometrial cancer by RESOLVE DWI and SS-EPI DWI was calculated according to pathological results. The difference between the RESOLVE DWI and SS-EPI DWI group was tested by Fisher’s exact probability method. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of judgment myometrial invasion by RESOLVE DWI and SS-EPI DWI were also calculated based on pathological results.The Spearman rank correlation test was used to assess the correlation of qualitative image quality scores between two readers. The correlation coefficient rho . All patients underwent operation within 2 weeks after the MRI examination. The types of operations were summarized in (Supplementary Table P < 0.001). Interobserver agreement of the depiction of geometric distortion, image blurring, ghosting artifacts, lesion conspicuity and overall image quality were good or excellent in two DWI sequences  × 10− 3 mm2/s, respectively. No statistical difference in ADC value was observed between SS-EPI DWI and RESOLVE DWI (P = 0.261).The average values of SNR for SS-EPI DWI and RESOLVE DWI were 51.37 ± 18.37 and 279.46 ± 109.48, respectively. The SNR values of the RESOLVE DWI were higher than those of SS-EPI DWI . 4 cases were wrongly staged by RESOLVE DWI and 10 cases were by SS-EPI DWI. The details were as follows: IA misdiagnosed as IB , IB misdiagnosed as IA , II misdiagnosed as IA (SS-EPI:1), IIIA misdiagnosed as IB , and IIIB case misdiagnosed as II  (Supplementary Table The accuracy of preoperative staging by RESOLVE DWI and SS-EPI DWI were 86.67% (26/30) and 66.67% (20/30) in endometrial cancer, respectively Table . The resAccurate preoperative evaluation of endometrial cancer lesions is very important for conservative treatment . This alThe increased cellularity of endometrial cancer causes restricted diffusion, which leads to increased signal on the DW image and a reduced ADC value . CompareQuantitative evaluation of DWI image quality includes SNR, CNR and ADC. The SNR is an important quantity used to describe the performance of an MRI system. The most commonly used technique is to determine the signal intensity in the tissue of interest and to measure the noise intensity in the image background. Gassert FT et al.  and GourThe results of the quantitative and qualitative analysis indicate that the image quality of RESOLVE DWI is better than that of SS-EPI DWI. The technique of RESOLVE DWI has proven to provide better detection and image quality in rectal, prostate, kidney, neck, and breast compared with SS-EPI DWI , 35, 36.The RESOLVE DWI typically is used to get higher resolution images. Our study found RESOLVE DWI images were more helpful to judge myometrium invasion in endometrial cancer. Although only the data in 95% confidence interval of sensitivity show that RESOLVE DWI is valuable in judging <50% superficial invasion. The values of specificity, PPV, NPV, and positive likelihood ratio in the RESOLVE DWI group were all higher than those in the SS-EPI DWI group. This may be related to our small sample study. The depth of myometrial invasion represents a prognostic factors in endometrial cancer, correlating with lymph node metastases and overall patient survival , 38. TheErrors in the assessment of myometrial invasion can occur in larger polypoid tumors, leiomyomas, congenital anomalies and very small atrophic uterus . CompareThere were several limitations in the study. First, the image quality of RESOLVE DWI and SS-EPI DWI was evaluated only in the axial plane. The combination of the sagittal and coronal images will make the results more accurate. Secondly, we found that the MRI imaging of endometrial carcinoma lesions could not be completely avoided some affecting factors. These factors include the size of endometrial cancer lesions, secretion of endometrial mucus, and the peristalsis of the intestinal canal. We need to expand the sample size, spend more time studying sequence conditions, and prepare patients for the intestinal tract to reduce the impact of these factors. Finally, the echo times of the two DWI sequences are significantly different (reflected in Table RESOLVE DWI can provide high quality images of endometrial carcinoma, which is helpful for the accurate assessment of myometrial invasion in endometrial carcinoma. The precise estimate will be helpful to select the suitable endometrioid adenocarcinoma patients for conservative treatment and monitoring the effects. It is also helpful to select the appropriate operative type and reduce the occurrence of surgical complications for the endometrial cancer patients .Additional file 1: Supplementary Table 1. FIGO Staging with Corresponding MR imaging.Additional file 2: Supplementary Table 2. MRI criteria for the assessment of myometrial invasion.Additional file 3: Supplementary Table 3. The operation methods in 30 patients.Additional file 4: Supplementary Table 4. Correlation analysis of qualitative scores between two observers.Additional file 5: Supplementary Table 5. Comparison of SS-EPI DWI and RESOLVE DWI in diagnosis of myometrial invasion and pathological results of endometrial carcinoma.


Numerous studies have reported on ovulation and pregnancy rates in patients with polycystic ovary syndrome (PCOS). However, relevant data on endometrial receptivity are limited. This study was conducted to compare endometrial receptivity during implantation windows among letrozole (LE), clomiphene citrate (CC), and natural cycle, and to assess the predictive value for pregnancy of observed indicators.This randomized controlled trial study enrolled 270 patients with PCOS. Patients were given LE (n=90) at a dose of 2.5mg/day or CC (n=90) at a dose of 50 mg/day on cycle days 5–9 for ovulation induction. Patients in the natural cycle group (n=90) did not receive any drug for ovulation induction. Endometrial ultrasonic parameters, integrin αvβ3, and vascular endothelial growth factor (VEGF) concentrations in uterine secretion were detected during the implantation window. The endometrial receptivity, ovulation rate, pregnancy rates, and predictive value of observed indicators for pregnancy were analyzed.P>0.05). Endometrial ultrasonic parameters , integrin αvβ3, and VEGF concentrations in uterine fluid were significantly higher in the LE group compared with the CC group and natural cycle group (P<0.05). The clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than in the CC group (P<0.05). Endometrial ultrasonic parameters , integrin αvβ3, and VEGF concentrations in uterine fluid of all pregnancy groups were significantly higher compared with the no pregnancy group (P<0.05), and the above parameters in ongoing pregnancy were significantly higher than in biochemical pregnancy (P<0.05). The endometrial FI during the implantation window had the highest predictive value for pregnancy (AUC=0.889). The integrin αvβ3 in uterine fluid had better predictive value (AUC=0.876) than VEGF.The successful ovulation rate did not differ between the LE group and CC group (Endometrial receptivity during the implantation window of LE is superior to CC in PCOS women, which may be related to higher clinical pregnancy and ongoing pregnancy rates. Endometrial FI examined by 3-D power Doppler, and integrin αvβ3 in uterine secretion during the implantation window, could be preferable non-invasive predictor markers for pregnancy.www.chictr.org.cn, ChiCTR1900023423. Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder in women of reproductive age, and its prevalence rate is from 9% (NIH criteria) to 18% (Rotterdam criteria) , 3. AbouEndometrial receptivity is critical for embryo implantation, and its impairment has been proven to be an important factor for infertility . In receNumerous studies have reported on ovulation and pregnancy rates between LE and CC in PCOS women. However, relevant data on endometrial receptivity during an implantation window are limited, especially the non-invasive methods of assessment. Because LE and CC have different mechanisms for ovulation induction, we presumed that their endometrial receptivity during implantation windows is different, which affect subsequent pregnancy. The aim of this study was designed to compare the endometrial receptivity among an LE group, CC group, and natural cycle group, and to assess the predictive value for pregnancy of observed indicators.www.chictr.org.cn (ChiCTR1900023423).We conducted a randomized controlled trial (RCT) study on PCOS patients with infertility in the outpatient clinic of obstetrics and gynecology and women’s health care. All participants gave written informed consent on the basis of procedures granted by the Ethics Committee of The First Affiliated Hospital of Medical College of Xi’an Jiaotong University (XJTU1AF2019LSK-120). This study has been registered on China’s clinical trials registration: 2 , combined with either hyperandrogenism or polycystic ovarian morphology . Hyperan2 . Hirsuti2 . Laborat2 . PatientPatients were pretreated with lifestyle interventions, improved hyperandrogenism, hyperinsulinemia, and insulin resistance. Then 270 patients were randomly divided into three groups according to computer-generated random numbers, with 90 patients in each group. Patients in the LE group received LE for ovulation induction (2.5mg/day on cycle days 5–9 of menses for 1 cycle), and patients in the CC group received CC for ovulation induction (50 mg/day on cycle days 5–9 of menses for 1 cycle). Patients in the natural cycle group did not receive any drug for ovulation induction.The follicle and endometrial thickness (ET) were detected using transvaginal ultrasound. Human chorionic gonadotropin (hCG) at a dose of 5000–10000 IU was used to trigger ovulation when a dominant follicle appeared (the average diameter ≥18 mm). The indicators of endometrial receptivity of patients with successful ovulation in the three groups were tested 7 to 9 days after ovulation (defined as embryo implantation window period). Color Doppler was used to test resistance index (RI) and pulsatility index (PI) of the uterine artery. Additionally, 3-D power Doppler ultrasonography was used to calculate endometrial volume (EV), flow index (FI), vascularization index (VI), and vascularization flow index (VFI) . MeanwhiThe diagnostic criteria for pregnancy were as follows: (a) serum hCG level exceed 10 mIU/mL tested at 2 weeks after ovulation was considered to be biochemical pregnancy; (b) appearance of pregnant bursa or embryo in the uterine cavity was considered to be clinical pregnancy; and (c) appearance of a fetus with a heartbeat at 12 weeks of pregnancy was considered to be ongoing pregnancy .The primary outcomes were endometrial receptivity and predictive value for pregnancy of observed parameters. The secondary outcomes were follicular development, ovulation, and pregnancy rates.t-test. The enumeration variables were presented as number and percentage (%), which were analyzed using chi-square test or Fisher’s exact test. Endometrial receptivity of observed parameters was evaluated using receiver operating characteristic (ROC) curves. P< 0.05 was considered statistically significant.Statistical analyses were performed using SPSS version 20.0. Normally distributed continuous data were given as mean ± standard deviation, which were analyzed by the analysis of variance or Student’s Two hundred and seventy-three PCOS patients were enrolled in this study, of which three patients were excluded. Hence, 270 patients were randomly assigned into three groups. There were 57, 55, and 11 patients with successful ovulation in the LE group, CC group, and natural cycle group, respectively. Endometrial ultrasonic parameters, integrin αvβ3, and VEGF in uterine fluid during the implantation window were tested Figure 1P>0.05).P<0.05), but the above indicators did not differ between the LE group and CC group (P>0.05). Moreover, no statistically significant differences were observed in diameter of dominant follicle, dosage of hCG, and LUFS rate among the three groups (P>0.05).P<0.05), but no statistically significant differences were observed in the above parameters between the CC group and natural cycle group (P>0.05). In addition, the data show that no statistically significant differences were observed in uterine PI and RI among the three groups (P>0.05).Among patients with successful ovulation in the three groups , the parameters of endometrial receptivity during embryo implantation were tested. The data in P<0.05). In addition, clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than that of the CC group  (P<0.05).The data from P<0.05). Moreover, the above parameters in ongoing pregnancy were significantly higher than that of the biochemical pregnancy group (P<0.05). However, no statistically significant differences were observed in uterine PI and RI, ET, and EV among the four groups (P>0.05).The patients with successful ovulation in this study were divided into four groups according to whether they were pregnant; 72 patients were in the no pregnancy group, 51 patients were in the biochemical pregnancy group, 39 patients were in the clinical pregnancy group, and 34 patients were in the ongoing pregnancy group. The data from Ovulation induction is regarded as an important therapeutic method for PCOS women with infertility. Previous studies reported that the ovulation rate of CC in PCOS women was 70%–80%. Nevertheless, the pregnancy rate was relatively low 25%–60%) . Scholars proved that this technology has better predictive value for endometrial receptivity than 2-D ultrasound, which has been used for in vitro fertilization-embryo transfer (IVF-ET)  . Yaman e(IVF-ET) . Our fin(IVF-ET) , which w(IVF-ET) . Similar(IVF-ET) . AdditioUterine fluid includes a variety of cytokines, which provide a suitable microenvironment for embryo implantation . PreviouAccording to the results of this study, clinical pregnancy and ongoing pregnancy rates of the LE group were significantly higher than in the CC group, which was consistent with previous studies. Wang et al. pointed out that LE improves clinical pregnancy and live birth rate compared to CC in women with PCOS . In anotThe present study still has some limitations. First, the RCT study was done in a single center. Additionally, the evaluative parameters were limited to one ovulation cycle, and live birth rate was not followed up. Second, endometrial receptivity is associated with many factors, including insulin resistance, hyperinsulinemia, thyroid hormone levels, abnormal immune-related indicators, haematologic parameters, and other cytokines. Therefore, multi-center studies with large sample sizes should be designed to verify the results of this research in the future.Endometrial receptivity during the implantation window of LE for ovulation induction is superior to CC in PCOS women, which may be associated with higher clinical pregnancy and ongoing pregnancy rates. Endometrial FI and integrin αvβ3 in uterine secretion during the implantation window could be preferable non-invasive predictor markers for pregnancy.All datasets generated for this study are included in the article/ supplementary material.The studies involving human participants were reviewed and approved by First Affiliated Hospital of Xi’an Jiaotong University Institutional Review Board. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.LW and XY contributed to the conception and design of the study. SL provided participants. FL and EB participated in data collection and patients’ follow-up. All authors contributed to the article and approved the submitted version.This study was supported by the Natural Science Basic Research Program of Shaanxi (Program No.2019JM-569) and by the Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University (Program No.2019ZYTS-03).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This prospective study aims to investigate the value of biologically relevant imaging biomarkers for predicting treatment response and survival outcomes in patients with locally advanced esophageal squamous cell cancer (LA ESCC).Perfusion CT can offer functional information about tumor angiogenesis, and 18F-FDG PET/CT using separate imaging systems before receiving definitive chemoradiotherapy (dCRT). The perfusion parameters included blood flow (BF), blood volume (BV), and time to peak (TTP), and the metabolic parameters included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The flow-metabolism ratio (FMR) was defined as BF divided by SUVmax. Statistical methods used included Spearman’s rank correlation, Mann–Whitney U test or two-sample t test, receiver operating characteristic (ROC) curve analysis, the Kaplan–Meier method, and Cox proportional hazards models.Twenty-seven patients with pathologically proven ESCC were included. All patients had undergone perfusion CT and r = 0.886, p < 0.001) and negatively correlated with SUVmax  and TTP  in the tumors. However, there was no significant correlation between perfusion and PET parameters. After dCRT, 14 patients (51.9%) were identified as responders, and another 13 were nonresponders. The BF and FMR of the responders were significantly higher than those of the nonresponders . The ROC curves indicated that the FMR [area under the curve (AUC) = 0.846] was a better biomarker for predicting treatment response than BF (AUC = 0.802). Univariable Cox analysis revealed that of all imaging parameters, only the FMR was significantly correlated with overall survival (OS) (p = 0.015) and progression-free survival (PFS) (p = 0.017). Specifically, patients with a lower FMR had poorer survival. Multivariable analysis showed that after adjusting for age, clinical staging, and treatment response, the FMR remained an independent predictor of OS (p = 0.026) and PFS (p = 0.014).The median overall survival (OS) and progression-free survival (PFS) were 18 and 11.6 months, respectively. FMR was significantly positively correlated with BF (The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and prognosis in ESCC. Esophageal squamous cell carcinoma (ESCC) is the most common pathological subtype of esophageal cancer (EC) in Asian countries, including China, accounting for approximately 90% of cases . DefinitUncontrolled, disordered, and sustained angiogenesis is a hallmark of cancer . Dynamic18F-fluoroglucose glucose positron emission tomography (18F-FDG PET/CT) is another molecular imaging technology that can reflect the glucose metabolism rate of tumors by quantifying FDG uptake. To date, it has been widely applied in ESCC patients for diagnosis, staging, response evaluation, and survival prediction  and metabolism parameters . This prospective study was approved by the Ethical Committee of Shandong Cancer Hospital and Institute. Informed consent was obtained from all participants prior to their inclusion in the study.Between January 2015 and September 2017, thirty-one patients newly diagnosed with ESCC and planning to undergo dCRT in Shandong cancer hospital and institute  were enrolled, and all met the following inclusion criteria: 18–75 years old; pathologically proven diagnosis of ESCC; no prior treatment; Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2; clinical stage IIb to III based on the 7th edition of the AJCC TNM classification; adequate hematological, liver and kidney function; and no history of other malignancies. The main exclusion criteria were pregnancy and a known allergy to intravenous contrast agents. All 31 patients underwent integrated perfusion CT/The perfusion imaging was performed on a 16-slice Philip Brilliance big bore CT scanner . The CT protocol includes two procedures. The first is unenhanced scanning of the neck/chest/upper abdomen to determine the tumor location; eight adjacent sections containing the maximum diameter of the lesion center were selected for cine imaging. The parameters used were as follows: slice thickness, 3 mm; speed, 30 mm/sec; pitch, 0.94; 120 kV; 120 mA; scan field of view, 30 cm; and matrix, 512 mm × 512 mm. The second step is a dynamic enhanced perfusion scan. In this step, the patients were first intravenously injected with 50 mL of a non-ionized iodinated contrast agent (300 mg/mL) at a rate of 5 mL/s through an 18-gauge cannula in the median cubital vein. After a 6-second delay, a dynamic scan  of the predetermined levels of interest  was started and lasted for 40 s .2. Finally, the average values of BF (in mL/100 g/min), BV (in mL/100 g), and TTP (in sec) were recorded as perfusion parameters for further analysis.All CT images obtained were transferred to a workstation  and were analyzed using commercially available software  based on the maximum slope method. We selected the descending aorta as the inflow artery and defined the arterial input as that through circular regions of interest (ROIs). Then, time-density curve (TDC) and functional perfusion maps were automatically generated . All patients were required to fast, rest quietly for more than 6 h before the scan, and ensure that their blood glucose concentrations were less than 6 mmol/L. Then, they were injected with 5.50–7.40 MBq/kg of 18F-FDG intravenously. After 60 min, whole-body PET and CT scans were performed from the top of the skull to the proximal thigh using the following scanning parameters: 140 kV, 80 mA, 6:1 pitch, 4.25-mm section thickness, 50-cm field of view, and 512 × 512 matrix. Patients were advised to relax and maintain normal shallow breathing during image acquisition. After CT-derived attenuation correction, the PET images were reconstructed by the ordered subset expectation maximization algorithm. The PET, CT, and fused images were transmitted to a Xeleris workstation  for transverse, coronal, and sagittal display.All images were independently assessed by two experienced nuclear medicine radiologists, and if there were inconsistencies, they were discussed until a consensus was reached. The values of SUV, MTV, and TLG were obtained through a vendor-provided automated contouring program. SUVmax was selected as the parameter to quantify FDG uptake, defined as the maximum voxel value of the SUV within the ROI. MTV represents the volume of tumor tissue with higher metabolic activity than the surrounding normal tissue, which is measured by fixed threshold method  in this study. TLG is the product of MTV and SUVmean, representing the combined volumetric and metabolic tumor burden. The flow-metabolism ratio (FMR) is defined as BF divided by SUVmax.18F-FDG uptake on PET images (SUV ≥ 2.5). The clinical target volume (CTV) included the primary tumor plus a 3-cm craniocaudal margin and a 1.0-cm margin in other directions as well as the metastatic lymph nodes plus a 1.0-cm margin. Planning target volume (PTV) was generated by 5-mm outward expansion of CTV in all directions. Considering that the radiation dose of 50.4 Gy may not sufficient for local control, all patients in our study received a total dose of 60–64 Gy with 30–32 fractions, which is a popular radiation dose in China. Chemotherapy started on day 1 of the initial radiation. The regimens consisted of cisplatin (75 mg/m2 on day 1) plus 5-fluorouracil (750 mg/m2 on days 1-3) or cisplatin (25 mg/m2 on days 1–3) plus docetaxel (60 mg/m2 on day 1), which were repeated every 21 days. Patients underwent 2 cycles of chemotherapy during radiation. After radiation, they received another 2 to 4 cycles of additional chemotherapy.All patients were treated with dCRT in a concurrent pattern. The radiotherapeutic technique used by all patients was the three-dimensional conformal radiation therapy or intensity-modulated radiation therapy by high-energy linear accelerators (6 MV). The gross tumor volume (GTV) included the primary tumor (GTVp) and metastatic lymph nodes (GTVnd), as shown by CT, PET/CT, esophagography, endoscopy, or endoscopic ultrasonography. The criteria for metastatic lymph nodes are those with a short diameter exceeding 1.0 cm or a long diameter exceeding 1.5 cm or those with a high Four weeks after treatment completion, based on comparison of the chest enhanced CT, esophagography before and after treatment, combined with the changes in patients’ clinical symptoms (such as dysphagia), the tumor response to dCRT was evaluated. According to the Revised Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria, the responses were divided into 4 categories: complete response , partial response , progressive disease , and stable disease ; patients who achieved CR and PR were considered responders, while those who were classified as PD and SD were identified as nonresponders. If the above examinations cannot determine the patient’s treatment response, the patient will be further scheduled for a second PET scan or biopsy to confirm. For example, using PET to determine the nature of newly emerging lesions during treatment (inflammatory or metastatic?), and use endoscope and biopsy to further determine the CR identified in imaging examination.Follow-up was performed every 3 months in the first year after treatment, every 6 months in the second year, and then every year thereafter until death or the last follow-up date. During the follow-up, arrange the necessary examinations for the patient according to their condition, including tumor markers, barium meal, contrast-enhanced CT, PET/CT, endoscope, and biopsy. Overall survival (OS) was defined as the time interval between the start date of dCRT and the date of death of any cause or the date of the last follow-up. Progression-free survival (PFS) was defined as the time interval between the start date of dCRT and the date of diagnosis of cancer progression  or the date of death for any reason. Follow-up methods include appointments for outpatient visits and telephone consultations. The last follow-up date was September 18, 2019.p < 0.05 was considered statistically significant. Quantitative parameters are expressed as the means ± standard deviations. Spearman’s rank correlation coefficient was used to assess the correlation between perfusion and metabolism parameters. The Mann–Whitney U test or two-sample t tests was used to compare these parameters between the responders and nonresponders. Receiver operating characteristic (ROC) curves were conducted to compare the ability of different factors to identify the responders. The Kaplan–Meier method was used to construct survival curves, and log–rank tests were used to compare the differences. Variables with p values less than 0.1 in univariable analysis were included in multivariable Cox proportional hazards model analysis.All statistical analyses were performed using SPSS version 22.0 and MedCalc 18.2.1. All tests were 2-sided, and 18F-FDG PET with a median interval of 7 days (range 3–10 days). The patient’s baseline characteristics are listed in Table One patient was diagnosed with a second primary lung cancer during treatment, and three patients discontinued dCRT and switched to surgery. So, they were excluded from analysis. Ultimately, the data from 27 patients  were included in the analysis. All patients were in clinical TNM stage IIb to III (T3-4N0-2M0). All patients underwent baseline perfusion CT and r = 0.886, p < 0.001) and negatively correlated with SUVmax  and TTP  in the tumors. However, there was no significant correlation between the perfusion parameters  and the PET-derived parameters    patients were classified as responders, including 4 CR and 10 PR, and the other half were identified as nonresponders . The baseline perfusion and metabolic parameters are listed in Table p = 0.002) was higher than that for BF , suggesting that the FMR was better for predicting response. However, the differences between AUC of BF and FMR were not statistically significant . This may be due to the small sample size that does not allow for sufficient statistical power.ROC curves were constructed to assess the diagnostic accuracy of BF and FMR in identifying the responders. As shown in Fig. p = 0.012). Similarly, there were also significant differences in the ORR between the high-FMR group and the low-FMR group .ROC analysis revealed that the optimal thresholds of the FMR and BF for predicting treatment response were 2.38  and 27.8 mL/100 g/min , respectively. The objective response rate (ORR) was significantly higher in patients with high BF than in those with low BF  with a minimum of 24 months for living patients. The median OS was 18 months , and the median PFS was 11.6 months . The patients were dichotomized into 2 groups according to the median values of each parameter. The Kaplan–Meier curves showed that the patients with a high FMR exhibited a longer OS (p = 0.026) and PFS . Unfortunately, treatment response had no independent predictive value for OS and PFS in the multivariate analysis, possibly due to the small sample size of our cohort or the interplay between FMR and treatment response.Table 18F-FDG PET/CT imaging provides a novel biomarker that better reflects the biological behavior of tumors than the individual imaging modalities, allowing us to better stratify patients with different clinical outcomes.In the present study, we measured tumor perfusion and metabolism in parallel in patients with LA ESCC who were going to undergo dCRT. Our preliminary results showed that the FMR can serve not only as a predictor of tumor response to therapy but also as an independent prognostic indicator for PFS and OS. The integration of perfusion CT and 18F-FDG PET/CT is a well-known imaging technology that can detect abnormalities in tumor glucose metabolism before changes in anatomical images can be observed, and it has been widely used in the clinical practice of EC [18F-FDG PET/CT clinically, there are a range of feasible techniques that can be used to measure tumor perfusion, such as perfusion CT, 15O-water PET, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) [Current advances in molecular and functional imaging have provided a range of noninvasive and accurate tools for mapping core hallmarks at the tumor level, including deregulated angiogenesis and metabolism. ce of EC . Howeverce of EC –15. ThisDCE-MRI) . In the DCE-MRI) , 24, 25.DCE-MRI)  and MakaDCE-MRI)  also appDCE-MRI) , 11. OurMany studies have explored the correlation between tumor blood perfusion and metabolic characteristics, and most have concluded that in many tumor types, including NSCLCs –27, headpeak ratio was not only able to predict OS but also outperformed other parameters. Although different from Komar’s study, Chen used PET-derived TLG and MRI-derived peaks instead of SUV and BF to quantify tumor metabolism and angiogenesis, and the conclusions were consistent, confirming that the flow-metabolism mismatch was correlated with poorer survival [The adaptive response of the tumor to hypoxia may indicate that the tumor has an aggressive biological phenotype and greater therapeutic resistance. Indeed, a number of studies have demonstrated that the flow-metabolism mismatch is closely related to poorer therapy response and long-term prognosis –19, 22. survival  concludesurvival . Our consurvival  or Mankosurvival . To the survival , 31. Gohsurvival  observedsurvival . TherefoAlthough the combined use of functional imaging is currently not very common, it is definitely a trend that can help us provide multifaceted and unique information about tumor characteristics and aggressiveness, thereby aiding in the development of individualized treatment plans. The results of our pilot study fully prove this point. For patients with a low FMR, it may be necessary to increase the intensity of chemotherapeutic drugs and the dose of radiation therapy or combine them with other therapies to control tumors and thus improve survival. In addition, multiparameter functional imaging may also provide valuable indicators for screening patients who may benefit from antiangiogenic therapy or immunotherapy, which will be the focus of future research.However, we must admit that the current research has some limitations. First, this is a small sample study with patients from a single center. Second, although we have used endoscopic ultrasonography, enhanced CT, and PET/CT to determine the clinical TNM stage, it may still not be as accurate as the pathological TNM stage, especially the N stage, because some metastatic lymph nodes are relatively small, and PET cannot recognize them. Third, we only focused on the impact of baseline perfusion and metabolic parameters on the therapy response and long-term survival of patients. In future research, we will dynamically monitor the changes in related parameters during chemoradiation and may find more valuable biomarkers. Finally, the threshold values of the FMR for predicting chemoradiotherapy sensitivity and survival were not determined, and further research is needed to clarify these values.The flow-metabolism mismatch demonstrated by a low FMR shows good potential in predicting chemoradiotherapy sensitivity and survival in ESCC. Therefore, as a promising biomarker, FMR may be helpful in the selection of personalized treatment, thus changing the management and improve the prognosis for ESCC patients.


Chronic lymphocytic leukemia (CLL) is an adult leukemia presented with clonal accumulation of lymphocytes. Immunophenotypic changes can be effective in predicting clinical course, the survival of patients, and determining first-line treatment. This is a study of the association between immunophenotypic markers with complete blood cell count (CBC) values and clinical parameters.Peripheral blood samples were collected from 35 newly diagnosed CLL patients. The expression of immunophenotypic markers and CBC were evaluated. Platelet counts and hemoglobin concentration had a significant, inverse association with Rai staging, modified Rai staging, Binet staging systems , and splenomegaly . The platelet/lymphocyte ratio (PLR) had a significant, inverse association with Rai staging (p = 0.014), modified Rai staging (p = 0.024), Binet staging systems (p = 0.027), and splenomegaly (p = 0.033). However, CD38, CD25, and double-positive CD56/CD117 expression, group 3 of innate lymphocyte cells (ILC3s), had no significant association with clinical parameters. In regression analysis, that ILC3s has an inverse correlation with neutrophil/lymphocyte ratio . Given that there is an inverse association between PLR and advanced clinical stages, it seems that PLR may have prognostic value in CLL. The platelet/lymphocyte ratio could be a prognostic marker which has correlation with an advanced clinical course in CLL.Lower platelet counts and Hb concentration association with advanced clinical course in CLL.There is an inverse correlation between innate lymphocyte cells and neutrophil/lymphocyte ratio in CLL.Chronic lymphocytic leukemia (CLL) is one of the most common types of adult leukemia. It presents with the abnormal clonal accumulation of B lymphocytes in peripheral blood (PB), bone marrow (BM), or tissues –3.CLL is categorized into prognostic groups based on the Rai and Binet clinical staging systems. In the Rai staging system, patients are classified into one of the five stages, stage 0 to IV, based on the presence or absence of lymphadenopathy, organomegaly, anemia, and thrombocytopenia , 5. In tCytogenetic and molecular characteristics of CLL cells can be helpful in predicting clinical course, the survival of patients and determining the first-line treatment , 7. ApprCLL cells are characterized by high expression of CD5, CD19, and CD23  and high− cKit (CD117)+ CD56+/− and divided into natural cytotoxicity receptor (NCR)+ (NKp44 and NKp46) ILC3s and NCR− ILC3s [Innate lymphoid cells (ILCs), that comprise of three groups , a family member of mononuclear hematopoietic cells, could play a key role in CLL pathogenesis by regulating adaptive immunity. ILC3s are characterized by CRTH22 (CD294)R− ILC3s , 13.Given the prognostic role of immunophenotypic markers in CLL patients, the aim of study was to assess the association between expression of CD38, CD25, and double-positive CD56 and CD117 (ILC3s) markers with peripheral complete blood cell count (CBC) values in CLL patients, and staging as defined by different schemes and clinical parameters.9/L, cell morphology according to French American British (FAB) criteria, clinical features, and atypical immunophenotype with CD19+, CD20+, CD5+, CD23+, Ig light chain (kappa and lambda) as revealed by flow cytometry. Patient staging was done considering Binet or Rai clinical staging systems was based on physical examination and the size of liver and spleen.We conducted a cross-sectional study confirmed from November 22, 2018 to September 21, 2019. The PB samples of 35 new CLL patients were collected. Patients were diagnosed according to the International CLL Workshop Criteria  and stagThree mL of PB from each participant was collected in ethylenediamine tetra-acetic acid tubes and these samples were processed within 6–24 h of collection. CBC was performed by the automated hematology analyzer. Having an important role in CLL diagnosis and progress, several parameters of CBC were selected, including white blood cell (WBC), platelet count, hemoglobin (Hb), absolute lymphocyte counts (ALC) and, absolute neutrophil counts (ANC).Patients’ PB samples were analyzed using three-color flow cytometry. The expressions of immunophenotypic markers in patients shown in Additional file All statistical analyses were performed using SPSS version 22, and data were expressed as median or interquartile range (IQR) for variables deviating from the normal distribution. Also, qualitative data were expressed as frequency and percentage. Normality was assessed by Kolmogorov–Smirnov test. We used the Mann–Whitney-U and Kruskal–Wallis tests to investigate the comparison of immunophenotypic markers or CBC results with clinical parameters. Spearman’s rho was used to study the correlation between nonparametric data. The level of significance was set at p < 0.05.Thirty-five CLL patients including 24 males and 11 females, with a ratio of 2.1:1  and the mean age of 64.34 years participated in this study. Results showed that (60.0%) of patients were at high-risk group, (17.1%) were at intermediate-risk group, and (22.9%) were at low-risk group. Almost half of the enrolled patients presented with splenomegaly (54.3%) and lymphadenopathy (31.4%). Regarding CBC results, (57.1%) of patients had anemia and (31.4%) thrombocytopenia. Clinical parameters, CBC and immunophenotypic markers of patients are summarized in Table The expression of immunophenotypic markers and CBC parameters were compared with clinical parameters Table . It was The results of the regression analysis showed that double-positive CD56/CD117 expression had a significant, inverse correlation with NLR  . This finding is consistent with that of Abdelgader et al. and Kamel et al. studies, which reported no significant association between CD38 expression and clinical parameters , 17. In Another finding was that CD25 expression had no significant association with clinical parameters. These results differ from Shvidel et al. and Grywalska et al. studies, it was reported that CD25 expression had a significant association with splenomegaly and Rai stage III , 22. UnlOur results did not show any significant association between ILC3s and clinical parameters , although we found an inverse correlation between these cells and NLR. Weerdt et al. in a similar study showed that ILCs count significantly increased in CLL patients and had a direct correlation with ALC and an inverse correlation with time to first treatment . It seemHere, it was shown that platelet count, Hb concentration, and PLR are significantly associated with Rai staging, modified Rai staging, Binet staging systems, and splenomegaly. So that, the platelet count, Hb concentration, and PLR were lower in patients in Rai stage IV, Binet stage C, high risk group or with splenomegaly. Similarly, Basabaeen et al. showed that thrombocytopenia was significantly correlated with splenomegaly . HoweverThe aim of study was to determine the prognostic role of immunophenotypic markers of CLL patients and their relevance to clinical parameters and hematological parameters. PLR had an inverse association with patients’ outcome, suggesting that it may have a prognostic value in CLL patients which requires further investigation. Moreover, we found that ILC3s had an inverse correlation with NLR, but it was difficult to arrive at any conclusion with regard to the prognostic role of these cells. Thus, further studies are required to determine the prognostic role of these cells in CLL patients.Patients were not followed up for the progression of CLL, survival rates and response to treatment.The prognostic role of cytogenetic findings of patients was not evaluated.The cytokine production as a marker for ILCs functionality was not evaluated.Additional file 1: Fig. S1. Representative flow cytometry profiles of immunophenotypic markers expression in patients with CLL. a) Sample of CD38 and CD25 expression.Additional file 2: Fig. S1. Representative flow cytometry profiles of immunophenotypic markers expression in patients with CLL. b) Sample of double-positive CD56/CD117 expression.Additional file 3: Fig. S2. A significant, inverse correlation between double-positive CD56/CD117 expression with neutrophil/lymphocyte ration (NLR)  in CLL patients.Additional file 4: Fig. S3. A non-significant, inverse correlation between double-positive CD56/CD117 expression with platelet/lymphocyte ration (PLR)  in CLL patients.


The prevalence of impaired cognitive functioning in older patients with end stage kidney disease (ESKD) is high. We aim to describe patterns of memory, executive function or psychomotor speed and to identify nephrologic, geriatric and neuroradiologic characteristics associated with cognitive impairment in older patients approaching ESKD who have not yet started with renal replacement therapy (RRT).2) prior to starting with RRT. In addition to routinely collected clinical parameters related to ESKD, such as vascular disease burden and parameters of metabolic disturbance, patients received a full geriatric assessment, including extensive neuropsychological testing. In a subgroup of patients (n = 93) a brain MRI was performed.The COPE-study (Cognitive Decline in Older Patients with ESRD) is a prospective cohort study including 157 participants aged 65 years and older approaching ESKD . A history of vascular disease (p = 0.007) and more white matter hyperintensities on brain MRI (p = 0.013) were associated with a lower psychomotor speed.The median age was 75.3 years. Compared to the normative data of neuropsychological testing participants memory performance was in the 24th percentile, executive function in the 18th percentile and psychomotor speed in the 20th percentile. Independent associated characteristics of impairment in memory, executive and psychomotor speed were high age, low educational level and low functional status (all Older patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD. Older patients approaching end stage kidney disease (ESKD) have, compared to younger patients, an increased risk for adverse health outcomes in general  and for , .., [8]. B, . If vasc, . Accumul, . Only a , . This tiIn the COPE study  we aimed2), and attending the pre-dialysis outpatient between April 2014 and December 2017. As part of routine pre-dialysis nephro-geriatric work-up, a comprehensive geriatric assessment (CGA), physical examination, laboratory investigation, neuropsychological testing and a brain MRI scan (in case there was no contra-indication) were performed. The study protocol was approved by the medical ethics committee (METC) of all participating centres.The full design of the COPE study, methods and rationale have been published previously . In brieAs part of routine pre-dialysis nephrogeriatric work-up, the following clinical parameters were measured: kidney function, metabolic state  and parameters on vascular status . eGFR was estimated glomerular filtration rate using the Modified of Diet in Renal Disease (MDRD)  or ChronAs part of the nephro-geriatric work-up, all patients underwent a comprehensive geriatric assessment (CGA). For a more detailed description of the tests used in the COPE study, see the previously published study protocol . Briefly, [Trained geriatric or dialysis nurses administered a standardized neuropsychological test battery. It was designed to assess different domains of cognitive functioning such as global cognition, visuoconstruction, memory, executive function and psychomotor speed. The test battery has been successfully used in several study cohorts over the past 20 years –23 and i, . To dist, .To compare the cognitive test results of the current study with a general population, Dutch normative data for neuropsychological tests corrected for age, gender and educational level were used this to interpret the cognitive status independent of age, gender and level of education . These n3), fluid-attenuated inversion recovery (FLAIR) images  = 1650 ms; voxel size 1.11 × 1.11 × 1.11mm3) and susceptibility-weighted imaging . The brain MRI scans were scored for markers of small vessel disease (white matter hyperintensities) and lacunes of presumed vascular origin and microbleeds) according to the STRIVE criteria [As part of routine nephro-geriatric work-up a brain MRI was performed in all patients without a contra-indication for MRI. Contraindications for not performing a MRI were: having a pacemaker, having a metallic foreign body  in their eye, being claustrophobic, or not being able to have access to the MRI table due to backpain or impaired mobility. Brain MRI scans were acquired on a Philips Ingenia 3 T scanners at the LUMC  according to a standardized scanning protocol. The scanning protocol included T1-weighted images (repetition time (TR) = 8.2 ms; echo time (TE) = 4.5 ms; flip angle 8°, voxel size 1x1x1mmcriteria . White mcriteria .normative data neuropsychological testing (see above). To assess associated characteristics of cognitive functioning in different domains, different cognitive tests are stratified in tertiles and mean scores of the different associated characteristics are calculated over the tertiles of cognitive functioning, presented as mean (standard error (SE)). Crude and adjusted p-values were calculated with univariable and multivariable linear regression models, respectively, with the continuous score of cognitive performance as dependent variable. In multivariable models we adjusted for age, gender and educational level, to ensure a balanced comparison between the tertiles. The MRI abnormalities were also assessed as determinant of cognitive function. The p-values are presented crude and adjusted . All analyses were carried out using SPSS .Baseline characteristics are presented as mean with standard deviation (SD) in case of normal distribution, median with interquartile range (IQR) in case of skewed distribution or as number (n) with percentages (%). Mean functioning on the different cognitive domains  are presented as percentiles (mean with IQR), according to the 2 (standard deviation (SD) 4.4) and over the past 3 years the mean decline in eGFR was 9.1 ml/min/1.73m2 (SD 8.0). In 99 (63%) patients a vascular cause, mainly hypertension or diabetes mellitus, was the cause of their primary kidney disease. Almost half of the participants  had a history of vascular disease. According to the Fried Frailty Index (FFI) 37 (25%) patients were frail. Functional dependence, as measured by the Instrumental Activities of Daily Living (IADL) with a score of ≥11, was found in 8 (5%) of the patients.Table Performance on the global cognitive function and different cognitive domains are reported in the Supplemental Table p-values ≤0.007). For example, the patients who performed in the worst tertile in memory function, compared to the best tertile, were on average 5 years older (p < 0.001) and more often received a lower educational level .In Tables p = 0.003). Patients who performed in the worst tertile of memory function were more functionally dependent compared to the patients who performed in the best tertile (mean IADL-score of 4.6 (SE 0.6) versus a mean IADL-score 2.0 (SE 0.4); p < 0.003). Having a history of vascular disease was associated with a more impaired memory function, although the association lost statistical significance after adjustment for age, gender and educational level. Parameters of metabolic disturbance were not associated with an impaired memory function.Table p < 0.001), the presence of frailty (p = 0.001) and a lower handgrip strength (p = 0.020) were significantly associated with a more impaired executive functioning. For example, in the tertile with the worst executive function, the presence of frailty was higher compared to the best tertile (mean Fried Frailty Index of 2.1 (SE 0.2) versus a mean Fried Frailty Index 1.0 (SE 0.2); p = 0.001). Having a history of vascular disease associated with an impaired executive function, although the association lost statistical significance after adjustment for age, gender and educational level. Parameters of metabolic disturbance were not associated with an impaired executive function.Table p = 0.001), a higher level of functional dependence (p < 0.001) and a lower handgrip strength (p = 0.026) were significantly associated with impaired performance on psychomotor speed. For example, the patients who performed in the worst tertile of psychomotor speed had a lower handgrip strength compared to the patients who performed in the best tertile (mean handgrip strength of 24.9 (SE 1.3) versus a mean handgrip strength 26.8 (SE 1.4); p = 0.026). After adjusting for age, gender and educational level, having a history of vascular disease was associated with an impaired performance on psychomotor speed (p = 0.007). Again, parameters of metabolic disturbance were not associated with an impaired performance psychomotor speed.Supplemental Table n = 93) are presented in Supplemental Table p = 0.013). A trend was observed for the association between a higher burden of white matter hyperintensities and lower executive function scores (p = 0.054).The cerebrovascular MRI features in a subpopulation n = 9 are presThe main findings of the present study were twofold. Firstly, impaired cognitive function, in the domains of memory, executive function and psychomotor speed was highly prevalent in patients approaching ESKD not yet started with RRT. Secondly, associated characteristics of a worse cognitive function in the domains memory, executive and psychomotor speed were older age, lower level education, lower functional status, frailty, higher burden of white matter hyperintensities on MRI and a history of vascular disease. Surprisingly, cognitive function was not influenced by parameters of metabolic disturbance.N = 385 median creatinine clearance of 19 ml/min) reported deficits in all cognitive domains, with the largest deficiencies found in recall, attention and executive function. We observed that associated characteristics of a worse cognitive function in the domains memory, executive and psychomotor speed were older age, lower education, lower functional status, frailty, higher burden of white matter hyperintensities on MRI and a history of vascular disease. In other populations with CKD, age, history of falls, functional status and a history of vascular disease were previously described as determinants associated with impaired cognition [In the present study, older patients approaching ESKD performed worse on all cognitive domains tested in comparison to the general population. This is consistent with findings in a study of younger patients attending a pre-dialysis clinic in where impairments in psychomotor efficiency and processing speed were more evident than impairments in the domains of learning efficiency or attention and working memory . Similarognition , 37. A nognition . The assognition –42. In oognition , 43. In There are several possible pathophysiological mechanisms that could explain the patterns and associated characteristics of cognitive impairment and the neuroradiological findings in older patients with ESKD described in our study. Firstly, it is possible that ESKD and cerebral vascular damage, are endpoints of the same pathophysiological pathway. Both the brain and kidney share similar vascular anatomy, as low resistance end organs exposed to high volume blood flow into their small vessels, and both have an auto-regulatory system. Because of this unique system, small vessels in kidney and brain, both afferent arterioles and deep perforating arterioles, are particularly prone to be injured by systemic hypertension and other vascular disease  as well Our results could have some clinical implications. When patients approach ESKD several treatment options, such as RRT including dialysis or transplantation or conservative treatment, are considered. When making treatment decisions, it is important to have insight into the cognitive function of the patient for several reasons. Firstly, cognitive impairment is independently associated with increased mortality, including in patients on RRT , 46. Sec2 and were not on RRT a study population that has previously only received limited scientific attention. Furthermore, this study focused exclusively on older patients (included median age of 75.3 (IQR 70.8–80.8)), a group whom very often do not participate in clinical trials due to exclusion criteria [There were several limitations to the current study. The study is integrated into routine clinical care and possibly has some patient selection bias. For example, the MRI brain is only performed in 60% of the participants, possibly causing some bias. Since the patients not having a MRI where older, more frail, more functional dependent and had a higher history of vascular disease the results described in our manuscript are probably underestimated. It could also be that the patients in worse condition were less likely to participate, which could result in an underestimation of the observed prevalence of cognitive impairment. The study has a relatively small group, which could cause a lack of power. The present analysis reported the cross-sectional association between several associated characteristics and cognition as a consequence that a causal association could not be established. Because of the fact there was not one primary analyses, and this was a post-hoc analysis, we did not perform a formal power calculation. We were however confident that our study provides sensible power to detect clinically relevant findings, because we did find all the known associated characteristics of cognitive function to be statistically significantly associated with cognition in all domains: higher age, higher education level, and higher disabilities in instrumental activities of daily living. Despite these limitations to our knowledge this was the first study in which cognitive function is described so extensively in combination with brain MRI’s in an older population approaching ESKD. The patients included in this study all had an eGFR < 20 ml/min/1.73mcriteria , 49. WitOlder patients approaching ESKD have a high prevalence of impaired memory, executive function and psychomotor speed. The patterns of cognitive impairment and brain changes on MRI are suggestive of vascular cognitive impairment. These findings could be of potentially added value in the decision-making process concerning patients with ESKD.Additional file 1: Supplemental Table S1. Performance on the different cognitive domains.Additional file 2: Supplemental Table S2. Associated characteristics of psychomotor speed.Additional file 3: Supplemental Table S3. Cerebrovascular MRI features in the study population.


Posterior reversible encephalopathy syndrome (PRES) is usually a benign, yet underdiagnosed clinical condition associated with subacute to acute neurological manifestations primarily affecting white matter. PRES is reversible when recognized promptly and treated early by removal of the insulting factor; however, can lead to irreversible and life-threatening complications such as cerebral hemorrhage, cerebellar herniation, and refractory status epilepticus.We utilized the National Inpatient Sample database provided by the Healthcare Cost and Utilization Project (HCUP-NIS) 2017 to investigate the demographic variables  for patients with PRES, concomitant comorbidities and conditions, inpatient complications, inpatient mortality, length of stay (LOS), and disposition.n = 455) and white as the most prevalent race. Half the patients in our study presented with seizures , sixty-three patients (9.9%) presented with vision loss, and sixty-four patients (10.1%) had speech difficulty. In addition, 45.5% of patients had hypertensive crisis (n = 289). 2.2% of hospitalizations had death as the outcome (n = 14). The mean LOS was 8.2 (±0.3) days, and the mean total charges were $92,503 (±$5758). Inpatient mortality differed between males and females (1.7% vs. 2.4%) and by race (3.6% in black vs. 1.8% in white) but was ultimately determined to be not statistically significant. Most patients who present with vision disturbance have a high risk of intracranial hemorrhage. Furthermore, end-stage renal disease, atrial fibrillation, and malignancy seemed to be linked with a very high risk of mortality.A total of 635 admissions for patients aged 18 years or older with PRES were identified. The mean age was 57.2 ± 0.6 years old with most encounters for female patients (71.7%, PRES, formerly known as reversible posterior leukoencephalopathy, is a neurological disorder with variable presenting symptoms. Although it is generally a reversible condition, some patients suffer significant morbidity and even mortality. To the best of our knowledge, this is the largest retrospective cohort of PRES admissions that raises clinician awareness of clinical characteristics and outcomes of this syndrome. Posterior reversible encephalopathy syndrome (PRES) is a clinical, radiographic syndrome ranging from subacute to acute neurological manifestations primarily affecting the white matter , 2. PRESPRES is still an underdiagnosed neurological syndrome with a constellation of symptoms that share characteristic neuroimaging findings , 3. DemoPRES is reversible when recognized early and treated promptly by removal of the insulting factor; nonetheless, it can lead to irreversible and life-threatening complications which include cerebral hemorrhage, cerebellar herniation, and refractory status epilepticus . In thisWe utilized the National Inpatient Sample database provided by the Healthcare Cost and Utilization Project (HCUP-NIS) 2017. This database is a weighted 20% sample of all-payer hospitalizations in the United States. The selection of these hospitalizations was made systematically by the Agency for Healthcare Resources and Quality (AHRQ) to represent all the hospitalizations in the United States in 2017. The data collected includes demographic variables, admission diagnoses, procedures, type of insurance, geographical location, length of stay, inpatient mortality, and disposition, among others. These encounters represent hospitalizations, not patients, so multiple potential hospitalizations for the same patient are considered as multiple encounters.We included all hospitalizations for patients primarily admitted for PRES. Encounters for patients aged < 18 years old were excluded from this study.We aimed to investigate the demographic variables  for these patients, concomitant comorbidities and conditions, inpatient complications, inpatient mortality, length of stay (LOS), and disposition.PRES and concomitant comorbidities and complications were identified through their international classification of diseases, 10th revision (ICD-10 codes) recorded in the discharge record for each hospitalization.http://privacyruleandresearch.nih.gov). The study was conducted in agreement with the principles of the Declaration of Helsinki.The NIS databases are considered “limited data sets” by the HIPAA privacy regulations; thus, do not require revision by an institutional review board (IRB) (t-test was used to compare continuous variables. Multivariate logistic regression models (Enter method) were used to predict outcomes, and Hosmer and Lemeshow (HL) test were used to assess goodness of fit. Variables that predicted outcomes in univariate analyses (p < 0.1) were included in the multivariate models. Correlation matrices were created and evaluated to rule out any potential multicollinearities. All analyses were done using IBM SPSS statistics version 26.0 . An alpha value (p) of 0.05 was used to ascertain statistical significance.Continuous and categorical variables were described as mean with standard deviation and frequencies, as appropriate. Chi-square was used to compare categorical variables, and an independent sample A total of 635 admissions for PRES were identified. Missing data were only 26 values in race variable and three values in primary expected payer. All analyses were done using pairwise deletion for missing data, as missingness of less than 5% of data is unlikely to introduce bias .n = 455). White was the most prevalent race. Medicare, followed by Medicaid, were the most common primary payers , sixty-three patients (9.9%) presented with vision loss, and sixty-four patients (10.1%) had speech difficulty. In addition, 45.5% of patients had hypertensive crisis (n = 289).Half the patients presented with seizures . Mean LOS was 8.2 (±0.3) days, and the mean total charges were $92,503 (±$5758). Inpatient mortality differed between males and females (1.7% vs. 2.4%); however, the difference was not statistically significant (p = 0.561). Mortality also differed by race (3.6% in black vs. 1.8% in white), but none of the differences were statistically significant (p = 0.786). Similarly, there was no statistical difference in length of stay between males and females. Ninety-one patients (14.3%) were documented to have cerebral edema. Twenty-nine patients developed intracranial hemorrhage (4.6%), while 32 patients developed cerebral infarction (5%). Regarding disposition out of the hospital, 67.4% (n = 428) were discharged home, while 18.22% (n = 115) were transferred to other facilities such as skilled nursing facility, intermediate care facility, inpatient rehabilitation, long term care hospital, among others, not including patients transferred to the hospital from other facilities.2.2% of hospitalizations had death as the outcome (p < 0.1) in univariate analyses. In a multivariate regression model only malignancy, atrial fibrillation, and ESRD predicted mortality (Table p = 0.88). Vision loss and hypertension predicted intracranial hemorrhage in univariate analyses (p < 0.1). However, only vision loss predicted intracranial hemorrhage , with HL showing a good fit (p = 0.97). ESRD and dehydration predicted cerebral infarction in univariate analyses (p < 0.1) although none of them predicted it in a multivariate logistic regression model.The predictability of different variables for unfavorable outcomes  was evaluated using univariate analyses Table . The prety Table  and the At present, the exact pathophysiology of PRES unknown; however, multiple theories have centered around the disruption of the blood-brain barrier (BBB) by an insulting factor leading to extravasation of intravascular fluid and cerebral edema . Rapid ePRES can present at any age and can range widely. Our average age of presentation for our patients was 57 years old; however, cases have been reported as old as 90 years old . PRES isPresenting symptoms of our patients were consistent with those observed in prior studies. The main symptoms included seizures and hypertension , 3, 6. Op = 0.003). The pathogenesis of parenchymal or sulcal subarachnoid hemorrhage in PRES could be due to either post-ischemic reperfusion damage or impaired autoregulation ) in patients with PRES, with the likelihood of dying about seven times higher than those without ESRD . Many studies revealed a heterogeneous association of renal diseases with PRES, ranging from no association in one series to approximately 30% in other large series [In our study, ESRD was a high predictor of mortality , which was consistent with prior studies [Our study found malignancy to be a strong predictor of mortality in PRES . A prior study by Hinduja et al. examining patients with PRES and predictability of intensive care unit admissions showed that all patients with atrial fibrillation required ICU admission [Atrial fibrillation was documented in approximately 10% of our patients with a odds ratio suggesting a four time higher risk of mortality . Severe infection or sepsis association with PRES was previously reported in the literature; however, was not well established as other comorbidities  [In our study, 198 patients 31.2%) had an associated severe infection or sepsis. These patients had a high odds ratio or mortality; however, this did not reach statistical significance  . Many thdisease) . Powerfu.2% had adisease) . FurtherPosterior reversible encephalopathy syndrome (PRES), formerly known as reversible posterior leukoencephalopathy, is a neurological disorder with variable presenting symptoms. Although it is generally a reversible condition, some patients suffer significant morbidity and even mortality. Upon reviewing the literature to date, this is the most extensive retrospective study of PRES admissions. Most patients who present with vision disturbance have a high risk of intracranial hemorrhage. Furthermore, ESRD, atrial fibrillation, and malignancy seemed to be linked with a very high risk of mortality. Ours is the largest study that raises awareness of PRES among the internists, neurologists, nephrologists, and hemato-oncologist and calls for a collaborative approach to mitigate the devastating consequences of this syndrome. Based upon the findings, we suggest prompt and meticulous fluid/electrolyte balance, blood pressure control, and avoidance of rapid changes from baseline, and chemotherapeutic agents in the management and reversal of this condition. Since kidney injury can be an important determinant of outcomes, further studies are needed to determine the impact and degree of renal insufficiency on PRES.


We found a strong positive association for infections among females, individuals not born in Australia or reporting heterosexual transmission being of non-B origin. Further, we found an overall increase in non-B infections among men who have sex with men from 50 to 79% in the last 10 years. However, we also found differences between non-B subtypes; heterosexual transmission was positively associated with subtype C only. In addition, the majority of subtype B infections were associated with clusters, while the majority of non-B infections were singletons. However, we found seven non-B clusters (≥5 sequences) indicative of local ongoing transmission. In conclusion, we present how the HIV-1 epidemic has changed over time in NSW, becoming more heterogeneous with distinct subtype-specific demographic associations. Changes over time in HIV-1 subtype diversity within a population reflect changes in factors influencing the development of local epidemics. Here we report on the genetic diversity of 2364 reverse transcriptase sequences from people living with HIV-1 in New South Wales (NSW) notified between 2004 and 2018. These data represent >70% of all new HIV-1 notifications in the state over this period. Phylogenetic analysis was performed to identify subtype-specific transmission clusters. Subtype B and non-B infections differed across all demographics analysed ( One of these, the circulating recombinant form 01_AE (CRF01_AE), is the most prevalent subtype in Southeast Asia . T. Tn = 23subtypes B. Most np < 0.001). Non-B subtypes were positively associated with infections among individuals that were female, not born in Australia, <30 years of age, living in postcodes with a gay male population of <5%, reporting heterosexual transmission, or being diagnosed during the advanced stage of infection (p < 0.001).The subtypes differed significantly in their associated demographics . First, p < 0.001, p < 0.001). In addition, significant differences were also found for age (p < 0.05), postcode according to gay male population (p < 0.001), transmission risk factor (p < 0.001), and stage of infection (p < 0.01)  . Subtypep < 0.05), but an increase from 27% to 46% among those not born in Australia (p < 0.01). We also observed a decrease in infections among individuals aged 20–29 years (p < 0.001) and in parallel a decrease among those aged 40–49 years (p < 0.01). No changes were found for transmission risk factor and stage of infection. For CRF01_AE we found significant changes over time for transmission risk, and stage of infection. We found an increase in infections among individuals reporting MSM transmission combined with a decrease in infections among individuals reporting PWID or other as a transmission risk factor (p < 0.05). Further, we observed an increase in infections among individuals diagnosed during the early stage (p < 0.05) combined with a decrease in infections among individuals diagnosed during the advanced stage (p < 0.01). We also found an increase in infections among MSM for subtype C and other subtypes and CRFs (p < 0.001) and this was combined with a decrease in infections among heterosexuals for subtype C (p < 0.05). No other demographics showed significant changes over time for subtype C and other subtypes and CRFs.We investigated changes over time between subtypes and different demographics for the time period 2009–2018 as it contained sufficient data for all subtypes analysed. Between 2009 and 2018, the changes in subtype-specific demographics over time differed for subtype B and non-B infections. This was most notable for region of birth and transmission risk factors . For subp < 0.01). However, we found an increase from 45% to 57% in the proportion of infections individuals living in postcodes with a gay male population of <5% (p < 0.01). We also found an increase from 15% to 30% for CRF01_AE infections among individuals living in postcodes with a gay male population of 5–19.9% (p < 0.05).A study by Callander et al. showed the vast discrepancy in the proportion of gay men and lesbian women living in different residential areas in NSW . They shPatterns of HIV-1 transmission were assessed by investigating sequence clusters for all subtypes. Overall, 232 sequence clusters and 165 sequence pairs were identified. For subtype B, 67% of all infections were associated with a cluster (>3 sequences) and 10% were associated with a sequence pair A. In conp < 0.001), as well as among heterosexuals, for being singletons (p < 0.01). Further, infections from notifications during the advanced stage were more likely to be singletons (p < 0.05). In addition, we found here that subtype B infections among individuals 50 years and older were also more likely to be singletons (p < 0.05).Finally, we compared demographics for infections in clusters and pairs and those that were singletons We report here on the growing diversity of HIV-1 in NSW. We show how non-B subtypes have increased over time, particularly among individuals reporting MSM as a transmission risk factor. We also show how subtype-specific demographics differ in general between subtype B and non-B subtypes, which also changed over time. In addition, we showed the importance of sequence data for epidemiological analysis as notification data alone do not represent the changes in genetic variability within an epidemic.p < 0.001). A large proportion of non-B subtypes infections among females has also been reported in the adjoining state, Victoria. In their study, Chibo et al. identified 85% of infections among female individuals reported in 2010 being of non-B origin [p < 0.01) but found no changes over time for any other subtype. The decline in advanced diagnosed for CRF01_AE infections was combined with an increase in diagnoses during the early stage of infection, which indicates an increase in early testing for individuals harboring CRF01_AE.Overall, we found significant differences between subtype B and non-B subtypes for all demographics analysed. Subtype B was strongly associated with male individuals and those born in Australia, while non-B subtypes were associated with female individuals and those not born in Australia. The strongest positive association was found for subtype C being among female individuals , for CRF01_AE 23% to 74%), and for other subtypes and CRFs (0% to 79%). This means that the observed decline in HIV-1 infections in NSW [% to 74%,Notably, we found changes for infections in individuals living in postcodes with a high or low proportion of gay male population. For subtype B, we found an increase in infections among individuals living in postcodes with a gay male population of <5% and a parallel decrease for infections among individuals living in postcodes with a gay male population ≥20%, indicating a shift from ‘gayborhoods’ to suburbs with low proportion of gay men. Our findings are consistent with the study by Grulich et al. that reported a 52% decline in HIV-1 notifications within postcodes in Sydney, NSW, where >10% of resident men identified as gay compared to 7% in other residential areas . Their sn = 7 infections, n = 5, n = 5), one CRF02_AG cluster (n = 7), one subtype A cluster (n = 6), and one CRF60_BC cluster (n = 5). However, only two of these clusters contained infections sampled in 2017 or 2018 that are indicative of recent local transmission. In addition, we found that while subtype B contained overall a majority of infections associated with clusters (67%), non-B subtypes contained a majority of infections that were either singletons or pairs. This means that non-B subtypes rarely lead to ongoing transmission in NSW.Finally, we quantified transmission clusters and found some clusters containing <5 sequences which are indicative of ongoing local transmission. Such subtype B and CRF01_AE clusters have been extensively described elsewhere (, acceptereverse transcriptase gene for phylogenetic analysis which might limit the depth of genetic clustering found here. However, we are using global data as background and thus clusters are defined by being more closely related to each other than to sequence data from other regions [This study had a number of limitations. Most notably, molecular data only include sequences from NSW, thus, we lack data from other states in Australia and might miss inter-state transmission. Further, we were only able to use the  regions . We alsoIn conclusion, we found significant differences in the demographic characteristics for newly diagnosed patients with different HIV subtypes. People with non-B subtypes were mostly foreign born, people with subtype C were mostly heterosexual, and people with other subtypes and CRFs were mostly 20–29 years old. Lastly, though limited, ongoing local transmission for non-B subtypes was observed in NSW. These data may assist with targeted prevention interventions and suggests that ongoing surveillance of HIV-1 molecular data is needed to continue to inform strategies aimed at virtual elimination of HIV in NSW.