Tendencies of problematic smartphone use (PSU) have risen during the past decade. As PSU is consistently linked to mental health issues, measures to prevent its appearance and to promote mental health are urgently required.Mage = 29.19, SDage = 10.51, range: 18–79) participated in the study. Over 14 days, the three experimental groups (a) reduced their daily smartphone use time by 60 minutes, (b) increased their daily level of physical activity by 30 minutes, and (c) combined both measures. The control group continued its behavior as usual. Outcomes were assessed via online surveys at five measurement time points .The present study investigated the impact of three interventions on health behavior, PSU, positive mental health (PMH), and depression and anxiety symptoms. Overall, 503 persons from Germany (All interventions resulted in a significant increase in weekly physical activity and in reduced symptoms of PSU, depression, and anxiety. Furthermore, the smartphone reduction and the combination of both measures contributed to a significant reduction of participants’ daily smartphone use and higher levels of PMH. The effects of the reduction of smartphone use time and its combination with increased physical activity were more stable in the longer term than the increase in physical activity only.Combined with an increase in physical activity, the reduction of smartphone use time could serve as an efficient and cost-effective measure for the prevention of PSU and the promotion of mental health. Smartphones are ubiquitous nowadays. Apart from the continuing growth in worldwide smartphone ownership O'Dea , the timNotably, not everyone who frequently engages in smartphone use develops addictive use tendencies. Recent research provides a theoretical framework for the explanation of this phenomenon. The Interaction of Person-Affect-Cognition-Execution (I-PACE) model  has been suggested as a possibility for reducing the negative impact of smartphone use on different health-related outcomes  reduction in smartphone use time, (b) increase in physical activity, and (c) a combination of both measures on longer term smartphone use and physical activity as well as on PSU and mental health. Previous research suggested past behavior to predict current behavior  and a control group (CG). The experimental manipulation lasted for 14 days. While participants of EG1 reduced their daily smartphone use, participants of EG2 increased their daily level of physical activity during this period. In EG3, participants reduced their daily smartphone use and increased their daily level of physical activity. The CG continued its smartphone use and physical activity as usual.According to Brailovskaia et al. , particiData for all groups were collected at five measurement time points via online surveys. Participants received the online links to the German-language surveys by email. Measurements took place 1 day before the 14-day experimental manipulation started , in the middle  and at the end  of the manipulation period, and 1  and 3 months  after the post-intervention measure. The intermediate and post-intervention measurement (T2 and T3) served for the investigation of short-term effects and the follow-up measurements (T4 and T5) for the investigation of the longer term effects of the experimental manipulation.Mage = 29.19, SDage = 10.51, range: 18–79) participated in the study. Participants were recruited through flyers that were distributed via mailing lists of different German universities and on social media platforms such as Facebook and Twitter. Calls for participation were also made via television, radio broadcasting, and on respective websites. Implementation of the present study was approved by the responsible ethics committee. Participation requirements included age of 18 years, ownership of a smartphone with a minimum of 1 hour of daily use, the ability to engage in physical activity for at least 30 minutes per day, and a maximum of 1 hour of daily physical activity under common circumstances . Participation was voluntary and compensated by course credits for students.Data collection took place from April 2021 to May 2022. Overall, 503 persons . At the beginning of the baseline survey, participants were properly informed about the study and provided informed consent to participate online. The 14-day intervention period started on the day after the baseline survey. After the 2-week period, participants of the experimental groups sent their compliance diaries back to the principal investigators. Compliance to the intervention was recognized when participants fulfilled their task for at least 9 of the 14 days of the intervention  who completed all surveys. All participants were Caucasian. Most of them were university students (57.8%) or employees (38.3%). The remaining participants were trainees (1.6%), freelancers (0.8%), or unemployed (1.6%); 46.9% were in a relationship but not married, 34.4% were single, 14.9% were married, and 3.9% were divorced. Analyses of the compliance diaries revealed a compliance rate of 85.2% (n = 109).Overall, 141 persons were assigned to the smartphone reduction condition. During the investigation period, 13 persons (9.2%) dropped out. Thus, EG1 comprised 128 participants , who were all Caucasian; 54.2% of them were university students, 40.8% were employees, 4.2% were freelancers, and one person (0.8%) was a trainee. Most of the participants were in a relationship but not married (52.5%), 30.0% were single, 15.8% were married, and two participants (1.6%) were divorced. Analyses of the compliance diaries revealed a compliance rate of 92.5% (n = 111).Overall, 145 persons were assigned to the physical activity increase condition. Since 25 persons (17.2%) dropped out, EG2 comprised 120 participants , so that 132 persons  were part of EG3. Half of the participants  were university students (50.8%), 42.4% were employees, 3.8% were freelancers, and 1.5% each were trainees or unemployed; 52.3% were in a relationship but not married, 27.3% were single, 19.0% were married, and two persons (1.5%) were divorced. Analyses of the compliance diaries revealed a compliance rate of 82.6% (n = 109).Overall, 146 persons were assigned to the combined condition where participants reduced their smartphone use and increased their level of physical activity. The dropout rate was 9.6% , who were all Caucasian; 51.2% of them were university students, 43.9% were employees, 3.3% were freelancers, and one participant each (0.8%) was a trainee or unemployed. In addition, 48.0% were in a relationship but not married, 27.6% were single, 22.0% were married, and 2.4% were divorced.Overall, 140 persons were assigned to the CG, who only answered the surveys. During the investigation period, 17 persons (12.1%) dropped out. Thus, the CG consisted of 123 participants  was required for valid results  showed that the participants did not differ regarding demographic variables. This applied for the comparison between the four groups as well as for the comparison of participants who dropped out and those who participated in all surveys. A priori power analyses using the G*Power program  accounted for rmtrr = 0.60 (EG1), rmtrr = 0.59 (EG2), rmtrr = 0.69 (EG3), and rmtrr = 0.58 (CG).Participants were asked to indicate their mean daily smartphone use in minutes. The current mean test–retest reliability calculated over all five measurement time points (rmtrr accounted for rmtrr = 0.44 (EG1), rmtrr = 0.38 (EG2), rmtrr = 0.28 (EG3), and rmtrr = 0.43 (CG).The weekly amount of physical activity was measured following the German Physical Activity, Exercise, and Sport Questionnaire  to very often (5). Brailovskaia et al. . In previous research, the scale reliability of the PMH-scale was α = 0.93  to 3 (applies to me very much or most of the time). Nilges and Essau  could have influenced the interventions.2p) served as the effect-size measure of main effects  and of interaction effects .Statistical analyses were conducted using SPSS 27 software. Datasets of the participants who answered all five surveys during the investigation period were complete. Thus, there were no missing data. After descriptive analyses, repeated-measures analyses of variance  were conducted to investigate short- and longer term effects of the different interventions as well as for the comparison of the four groups. Because of a significant Mauchly’s test, the Greenhouse–Geisser adjustment  = 25.591, p < 0.001, η2p = 0.049), a nonsignificant main effect for group condition  = 1.464, p = 0.224, η2p = 0.009), and a significant interaction effect  = 4.301, p < 0.001, η2p = 0.025). Pairwise comparisons within groups indicated a significantly lower smartphone use at T3, T4, and T5 compared with baseline (T1) in EG1 and EG3. These effects were stronger in EG1 than in EG3. Further, there was a significant decrease from T4 to T5 in EG1 . Pairwise comparisons between groups revealed a significantly lower smartphone use at T5 between EG1 and all the other groups (EG1 < EG3 < EG2 < CG). While the effects of the differences between EG1 and the two other experimental groups were small, the effect of the difference between EG1 and CG was moderate.Results of the ANOVA for daily smartphone use time revealed a significant main effect for measurement time point  = 26.674, p < 0.001, η2p = 0.051), a significant main effect for group condition  = 2.651, p = 0.048, η2p = 0.016), and a significant interaction effect  = 5.127, p < 0.001, η2p = 0.030). In all three experimental groups, there was a significant increase in physical activity from baseline to post-intervention measurement (T3), with a small effect in EG1 and large effects in EG2 and EG3. After the initial increase, there were significant decreases from T3 to the follow-up measurements T4 and T5 in EG2 and EG3, with small (EG2) and moderate (EG3) effects. However, the level of physical activity was higher at all measurement time points in comparison with baseline in EG2 and higher at post-intervention and follow-up 2 than at baseline in EG3. Pairwise comparisons between groups indicated higher physical activity levels at post-intervention measurement in EG2 and EG3 in comparison with EG1  and CG (medium effect sizes).For weekly physical activity, the ANOVA displayed a significant main effect for measurement time point  = 14.195, p < 0.001, η2p = 0.028), a nonsignificant main effect for group condition  = 0.990, p = 0.397, η2p = 0.006), and a significant interaction effect  = 6.788, p < 0.001, η2p = 0.039). While the level of PSU in EG1 did not change significantly from T1 to T3, there were significant decreases from T3 to T4 and T4 to T5 . The effect size of the differences between PSU at follow-up 1 in comparison with its levels at baseline and intermediate measurement (T2) was small, that of the comparisons with follow-up 2 was medium. In EG2, the level of PSU was lower at post-intervention than at baseline . In EG3, it was lower at all measurement time points in comparison with baseline . According to pairwise comparisons, the level of PSU at T2 and T3 was higher in EG1 than in EG2 . However, it was lower in comparison with CG at follow-up 2 .Concerning PSU, results of the ANOVA displayed a significant main effect for measurement time point  = 4.520, p = 0.002, η2p = 0.009), a nonsignificant main effect for group condition  = 1.472, p = 0.221, η2p = 0.009), and a significant interaction effect  = 2.295, p = 0.010, η2p = 0.014). A similar result pattern was found in EG1 and EG3: while the level of PMH did not differ between baseline and T2 and T3, respectively, it was higher at follow-up 1 and 2 in comparison with baseline . The only difference between the groups was found at follow-up 2, with higher PMH values in the EG1 than in the CG .Considering PMH, the ANOVA revealed a significant main effect for measurement time point  = 7.662, p < 0.001, η2p = 0.015), a nonsignificant main effect for group condition  = 1.010, p = 0.388, η2p = 0.006), and a significant interaction effect  = 1.927, p = 0.032, η2p = 0.011). While the only difference between measurement time points was between T1 and T5 in EG1 (with a lower level at T5), the level of depressive symptoms was lower at post-intervention in comparison with baseline in EG2. Both effect sizes were small. In EG3, depressive symptoms were lower at all measurement time points compared with baseline . Considering group differences, again, there was only a difference between EG1 and CG at follow-up 2, with a lower level of depressive symptoms in EG1 .Regarding depressive symptoms, the ANOVA pointed to a significant main effect for measurement time point  = 11.865, p < 0.001, η2p = 0.023), a nonsignificant main effect for group condition  = 2.095, p = 0.100, η2p = 0.012), and a significant interaction effect  = 2.696, p = 0.002, η2p = 0.016). In EG1, the level of anxiety symptoms was significantly lower at follow-up 1 and 2 compared with baseline . In EG 2 and EG3, it was significantly lower at T2, T3, and T4 in comparison with baseline, with small to medium effect sizes. After this decrease, there was a slight increase  from post-intervention to follow-up 2 in EG3. Pairwise comparisons between groups indicated a significantly lower level of anxiety symptoms in EG1 than in CG at T5 .Results of the ANOVA for anxiety symptoms revealed a significant main effect for measurement time point . Thus, the participants could use the newly available time to engage in physical activity. This is in line with the displacement hypothesis, which posits that time spent on digital devices takes time away from other activities and health behaviors like physical activity or supportive social interactions . The engagement in physical activity can fulfill different psychological needs . This might be explained by the negative symptoms within the craving stage . Apart from its influence on the physical activity level, the reduction in daily smartphone use time by 60 minutes was more effective than the increase in daily physical activity by 30 minutes considering the smartphone-related constructs of daily use time and PSU, PMH, and symptoms of depression and anxiety (see Research Question 2). Furthermore, the combination of both measures was of great benefit. It yielded positive effects similar to the reduction in smartphone use time alone. However, these positive effects partly occurred earlier than the effects of the reduction alone (see Research Question 2). Thus, experiencing the positive effects earlier in time might motivate persons to further engage in a healthier lifestyle. However, the effects of the reduction in smartphone use time alone were often more stable (see Research Question 2). Therefore, it could be beneficial to modify the increase in physical activity : instead of asking individuals to increase their daily physical activity level by 30 minutes for 2 weeks, it seems desirable to offer structured, group-based programs for several months (e.g., Eime et al. To summarize, all three interventions had a positive effect on the investigated variables. However, they differed in their effectiveness (see Despite the practical significance of the current results, some limitations of the present study are noteworthy. First, most of the effect sizes were small to medium. As non-compliers were kept in the sample for the analyses, the results can be considered as conservative estimates of the true treatment effects which might be larger in size Tromholt . HoweverIn summary, over the past decade, significant increases have been noted in smartphone screen time (Harvey et al.


To explore the feasibility of 3D printing-assisted pedicle screw correction surgery for degenerative scoliosis.  From January 1, 2015 to January 31, 2020, patients with degenerative scoliosis who received corrective surgery in our hospital were retrospectively analyzed. Patients were grouped based on the fixation methods. Patients in the control group received traditional pedicle screw internal fixation, while those in the study group received 3D printing-assisted pedicle screw fixation. The therapeutic effects were compared.  There were 78 cases in the control group and 82 cases in the study group. There were no significant differences in scoliotic Cobb's angle, pelvic incidence-lumbar lordosis (PI-LL), VAS score, JOA score, social function, physical function, role function, or cognitive function between the study group and the control group before the surgery, but there were differences in the above parameters between the two groups after surgery. The incidence of postoperative complications in the study group was also significantly lower in the study group.  3D printing-assisted pedicle screw correction surgery provides a strong 3D correction force with reliable effect and fewer complications, and is a good treatment choice for degenerative scoliosis. In degenerative scoliosis, the deformity of the spine is three-dimensional (3D) and rotational due to the progression of the lesions in the vertebrates. The Cobb angle is characteristically over 10°. The lesions initiate as asymmetric degeneration in the disc and joints, producing asymmetric loading and subsequent deformity. The symptoms include pain with neurological deficits. Nonsurgical treatment includes medication and physical therapy. Alternatively, epidural injections for selective nerve root blockade may be used . In patiThis study included patients who received degenerative scoliosis and correction surgery at our hospital from January 1, 2015, to January 31, 2020. The ethics committee of our hospital approved this study. All included patients and their families were informed of the study and actively signed informed consent. The inclusion criteria were: (1) Clinically confirmed degenerative scoliosis; (2) corrective surgery required; and (3) normal cardiopulmonary function. The exclusion criteria were: malignant disease, mental illness, drug allergy, any previous treatment of degenerative scoliosis with surgeries or medications, chronic diseases that need long-term medication such as hypertension, diabetes, etc., or lost-to-follow-up.All patients received frontal and lateral X-ray photography of the whole spine before surgery for determination of the patient's scoliosis and rotation; left and right refractive photography and suspension traction photography were used to determine the patient's spine elasticity as well as the largest orthopedic angle of the patient during the operation. MRI scans and CT scans of the spine were performed before the operation to determine whether there were lesions with or without neural structures such as spinal cord cavities and cauda equina and to determine the actual rotation angle of the pedicle of the rotational deformity. The minimum diameter of the pedicle lays the foundation for the determination of intraoperative positioning and screw insertion angle. At the same time, pulmonary function tests, somatosensory evoked potentials, and action evoked potentials were performed to determine whether there was damage to other organs. Before the operation, conventional spinal traction therapy was used to relax the small joints of the cervical spine, and the adaptability of the nerves in each group to stretching was observed. Patients in the control group received traditional pedicle screw internal fixation. Patients in the study group were treated with 3D printing-assisted pedicle screws for 3D fixation [The visual analog scale (VAS) score, Japanese Orthopaedic Association Evaluation Treatment (JOA) score, quality of life score, scoliosis Cobb's angle, pelvic incidence-lumbar lordosis PI-LL, , and posn, %) were analyzed by χ2 test, and the measurement data (‾x ± SD) were analyzed by t-test. P < 0.05 (two-sided) represents statistical significance.The data in this experiment were analyzed by SPSS21.0 , in which the count data . The clinical characteristics of the patients were shown in A total of 160 eligible patients  were retrieved. The average age of patients in the control group was (56.96 ± 5.02) years old, and that in the study group was (56.51 ± 6.36) years old. There were no differences in gender, age, and past medical history between the two groups . After surgery, Cobb's angle of scoliosis (5.10 ± 0.32) and PI-LL (13.92 ± 0.37) in the study group were lower than those before surgery  or PI-LL (35.51 ± 0.56 vs 35.23 ± 0.49) between the study group and the control group before surgery  before surgery. After surgery, there were significant differences in the VAS score (3.10 ± 0.18 vs 4.41 ± 0.56) and JOA score (23.42 ± 0.36 vs 19.50 ± 0.51) between the study group and the control group  or JOA score (12.57 ± 0.38 vs 12.26 ± 0.50) between the study group and the control group . After surgery, there were significant differences in the social function (82.84 ± 1.15 vs 79.13 ± 3.20), physical function (84.50 ± 3.80 vs 75.44 ± 4.26), role function (83.30 ± 5.38 vs 76.82 ± 6.34), and cognitive function (80.61 ± 4.85 vs 74.35 ± 3.52) between the study group and the control group , physical function (64.23 ± 5.51 vs 64.35 ± 5.08), role function (67.00 ± 6.02 vs 66.53 ± 6.25), or cognitive function (62.97 ± 4.28 vs 64.33 ± 3.14) between thestudy group and the control group (P=0.001, There was a significant difference in the total incidence of postoperative complications between the study group and the control group P=0.001, .Degenerative scoliosis occurs through degenerative changes without pre-existing spinal deformity, and it is generally more common in older age groups. It is presented with asymmetric disc space collapse and facet degeneration followed by lateral and/or rotational sliding . This coAbout 90% of those patients mainly present with pain, muscle fatigue, and spasticity of scoliosis causing diffuse and axial low back pain in most patients. Judging from the fluoroscopy-guided articular surface injection, all of these people have low back pain due to articular surface degeneration , 13. ThePedicle screw fixation is aided by 3D printing . The thrTo sum up, 3D printing-assisted pedicle screw 3D correction surgery provides a powerful 3D correction force with reliable effect and few complications, and is effective in dealing with degenerative scoliosis.


Neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR), and systemic immune‐inflammation index (SII), easily accessible systemic inflammation response parameters, were reported to associate with poor lung cancer prognosis. However, research on the effects of these markers on the risk of positive nodules (PNs) and lung cancer is limited.Participants in this retrospective study were those who had their first computed tomography (CT) screening at Jiangsu Province Hospital's Health Promotion Center between January 1, 2017 and December 31, 2020. We identified PNs (≥6 mm in diameter) from free text of CT reports and lung cancer from medical records. Multivariate logistic analysis was used to assess the association between NLR, PLR, or SII and PNs or lung cancer.pnon‐linear > 0.05). Compared with low quintile, participants with top quintiles of NLR, PLR or SII had an increased risk of PNs, with the adjusted ORs of 1.19 (1.11–1.28), 1.11 (1.04–1.19) or 1.11 (1.03–1.18), respectively. Meanwhile, NLR showed the U‐shaped relationship with lung cancer, with adjusted ORs of 1.40 (1.08–1.81) comparing highest NLR quintile to the third quintile. The high PLR and SII showed significantly associated with lung cancer with adjusted ORs of 1.29 (0.99–1.68) and 1.35 (1.04–1.74) comparing to the lowest quintile.The detected rate of PNs was 9.60% among the 96,476 participants. Age, smoking and body mass index were possible influencing factors for PNs. We observed linear dose‐effect relationship between NLR, PLR, or SII and PNs  was 9.60%. We also found that elevated Neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and systemic immune‐inflammation index (SII) were associated with increased risk of positive nodules identification. Then, high levels of these three markers showed significantly associated with lung cancer. Firstly, we evaluated the initial detection rate of positive nodules in populations with different characteristics. Then, we evaluated whether NLR, PLR or SII was associated with identification of positive nodules. Furthermore, we also examined whether or not there were links between these markers and lung cancer risk.22.1In China, employees are required to undergo annual or biennial health examination. Health Promotion Center of Jiangsu Province Hospital mainly provide comprehensive care for examinees in Nanjing, where about 75% were employees of various companies or local governmental agencies. This center implemented an electronic medical record system in 2014, which stores data on sociodemographic, diagnoses, laboratory tests, comorbidities, medical history, and radiology and so on. Structured data and free‐text radiology reports were retrieved from this electronic medical system and used in this study.The approval was obtained from ethics committees at Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University. Analyses were conducted using anonymized and de‐identified data, and thus informed consent was not required.2.2N = 112,629). In this retrospective analysis, we extracted data from the participants’ first chest CT as baseline data, even if the participants underwent more than once chest CT during this period. Subsequently, we used a structured processing methodThis was a retrospective study of adults over the age of 18 who voluntarily underwent a comprehensive health examination and chest CT imaging at Health Promotion Center of Jiangsu Province Hospital between Jan 1, 2017 and Dec 31, 2020 (N = 440); (2) a history of other malignancy (N = 4175); (3) missing data on smoking status, body mass index (BMI), platelets, neutrophil, lymphocyte, and monocyte ; (4) lung mass (>3 cm in diameter) (N = 43). In total, there were 96,476 participants who were eligible to take part in this study  a history of lung cancer or lung surgery  were self‐reported by participants. For this study, participants were categorized into never‐smokers and ever‐smokers. Participants were classified as never‐smokers if they had never smoked or if they had smoked <100 cigarettes in their lifetime.2 (square meter). Blood pressure (BP) was recorded by trained nurses with an electronic sphygmomanometer after at least 5 min of seated rest. Hypertension was defined as a self‐reported history of hypertension, or BP ≥140/90 mm Hg.1c) ≥6.5%, or fasting blood glucose (FBG) ≥7.0 mmol/L.For each participant, BMI was calculated as weight (kilogram)/height9/L) and platelet count  by the lymphocyte count , respectively. The SII was defined as follows: SII = P×N/L.Blood samples were taken from participants after at least a 10‐h fast. White blood cell count, neutrophils, lymphocytes, platelet, eosinophil, and basophil count were measured using the same automatic hematology analyzer. NLR and PLR were calculated by dividing the absolute neutrophil , Q2 (1.28‐ < 1.57), Q3 (1.57‐ < 1.88), Q4 (1.88‐ < 2.33) and Q5 (≥2.33); PLR was categorized into quintiles as follows: Q1 (<87.11), Q2 (87.11– < 104.92), Q3 (104.92– < 122.77), Q4 (122.77– < 147.40) and Q5 (≥147.40). SII was categorized into quintiles as follows: Q1(<262.06), Q2 (262.06– < 336.92), Q3 (336.92– < 418.21), Q4 (418.21– < 540.65), Q5 (≥540.65). As appropriate, data are presented as mean  or as number (percentage). T‐tests for continuous variables and Chi‐squared tests for categorical variables were used to analyze baseline characteristics.The endpoints were the occurrence of positive pulmonary nodules and incident lung cancer. Data of their first screen (baseline data) were used to evaluate the associations between three markers and positive nodule or lung cancer. We computed the odds ratios (ORs) and 95% confidence intervals (CIs) for positive nodule or incident lung cancer using logistic regression models to compare each category of markers among overall populations. Further adjustments were made to the multivariable model for age (continuous variables), gender , smoking status , BMI (continuous variables), diagnosed hypertension , diagnosed diabetes , and diagnosed lung diseases . To assess the concentration‐response relationship between markers and positive nodules identification, we modeled NLR, PLR, or SII as restricted cubic splines with knots at the quartiles of the sample distribution.To investigate the potential source of heterogeneity, subgroup analyses were performed by age, gender, smoking status, BMI. Using likelihood ratio tests, we compared models with and without multiplicative interaction terms to see if there were any interactions between NLR, PLR, or SII categories and subgroup characteristics.p‐values were two‐sided and p < 0.05 was considered statistically significant. Analyses in this study were performed using STATA software version 16 (STATA Corp) and R software version 3.6.1 .All 33.1p < 0.001). Male participants account for about 60.62% of the total populations, and the gender distribution was similar between groups. The proportion of ever‐smokers with positive nodules was larger than the other group . Compared with participants without positive nodules, those with positive nodules more likely to have underlying diseases . The mean values of platelets, neutrophil, lymphocyte, monocyte counts were differed significantly between groups. The mean values of NLR, PLR and SII in participants with positive nodules were higher than the other group . Baseline characteristics are shown by NLR quintiles, PLR quintiles and SII quintiles  with incidental positive pulmonary nodules. The baseline characteristic of participants was listed in Table s Tables  and S3.3.2p < 0.001). Ever‐smokers have higher detection rates of positive nodule than never‐smokers . The rates were 9.52% and 9.66% for adult women and men, respectively (p = 0.486). Participants with normal BMI (18.5–22.9 kg/m2) have slightly low detection rate (9.07%). When a multivariable model was used to further evaluate the associations, age, BMI and smoking were found to be possible influencing factors for positive pulmonary nodules , PLR (pnon‐linear = 0.4151) or SII (pnon‐linear = 0.1877) and positive nodules identification with the restricted cubic spline analysis. Then, we grouped the overall participants into five levels according to quintiles. After adjusting for age, gender, BMI, smoking status, diagnosed hypertension, diagnosed diabetes and diagnosed lung diseases, the adjusted OR (95% CI) for positive nodules identification in quintiles 2, 3, 4 and 5 of NLR when compared to the lowest quintile were 1.04 (0.96–1.11), 1.07 (1.00–1.15), 1.08 (1.01–1.16) and 1.19 (1.11–1.28), respectively . As shown in Table p for quadratic term = 0.0145). Higher PLR and SII quintiles showed significant association with lung cancer risk when compared to the lowest PLR quintile group (OR = 1.29 (0.99–1.68) and 1.35 (1.04–1.74) for the highest PLR and SII quintile, Table p for interaction >0.05, Tables Up to date of December 1, 2021, 569 of all participants were diagnosed as lung cancer cases. Table 4In this large retrospective analysis of Chinese population participating in health‐screening exams, elevated NLR, PLR or SII were associated with increased risk of positive nodules identification. Furthermore, U‐shaped association was observed between NLR and lung cancer. However, the high NLR, PLR, and SII showed significantly associated with incident lung cancer. These findings may suggest that systemic inflammation may associated with the occurrence of positive nodules and lung cancer risk.Recently, with the increased emphasis on routine health examinations and popularity of chest CT scans, numerous subjects with incidental pulmonary nodules has gradually increased.NLR, PLR, and SII are markers of systemic inflammation response. There has been no prior research that explored the relationship between these three markers and the identification of positive nodules. Fortunately, this study with large sample size firstly examined the association between these markers and positive nodules identification in overall populations. Our study demonstrated that the high NLR or PLR may associate with high risk of positive nodules. More than 95% of detected nodules are benign and the most common cause is a previous infection.To the best of our knowledge, inflammation microenvironment plays a crucial role in carcinogenesis.Several limitations should be noted in this current study. Firstly, although we used structured processing method and manual review for nodule identification, some ambiguous or nonspecific terminology in CT reports may have resulted in missed incidental nodules since no images were reviewed. This should be considered when interpreting our estimates. Secondly, smoking status was self‐reported and was therefore subject to reporting biases. Due to the lack of standard questionnaire, participants did not report the detailed information of smoking exposure such as duration of cessation, cigarette consumptions. These problems should be improved in the further study. Thirdly, despite the large‐scale populations, the included participants were restricted in the single center. The lung cancer cases should be followed up for a longer time. Finally, this study was a population‐based cross‐sectional analysis. To better explore the causal effect, further robust epidemiological evidence, like cohort study, is urgently needed.In conclusion, in this large retrospective study of healthy populations, high NLR, PLR, and SII, easily accessible systemic inflammation response parameters, were associated with positive nodules and incident lung cancer. These results may indicate that systemic immune response may be an important pre‐clinical feature for the early identification of disease.None.Dr Qun Zhang and Dr Hongbing Shen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Ting Tian, Jing Lu; Acquisition, analysis, or interpretation of data: Wei Zhao, Zhongming Wang, Hai Xu, Yuqing Ding, Wen Guo; Pei Qin; Wenfang Zhu; Ci Song; Drafting of the manuscript: Ting Tian, Jing Lu; Critical revision of the manuscript for important intellectual content: Hongbing Shen, Qun Zhang, Hongxia Ma, Ci Song; Statistical analysis: Ting Tian; Obtained funding: Hongbing Shen, Qun Zhang, Ci Song, Ting Tian; Administrative, technical, or material support: All authors;The approval of this study was obtained from ethics committees at Jiangsu Province Hospital and the First Affiliated Hospital of Nanjing Medical University.Analyses were conducted using anonymized and de‐identified data, and thus informed consent was not required.Appendix S1Click here for additional data file.Figure S1Click here for additional data file.Figure S2Click here for additional data file.


N––1H–pyrazole–4–carboxamide  and further N–glycosylated to 3–(difluoromethyl)–1–(ß–D–glucopyranosyl)–N––1H–pyrzaole–4–carboxamide .The risk quotients of the total fluxapyroxad for the urban groups were significantly higher than those for the rural groups, and were both negatively correlated with the age of the groups, although both acute  and chronic  risks are acceptable for the human population. The high-potential health risks of fluxapyroxad should be continuously emphasized for susceptible toddlers (1–3 years), especially those residing in urban areas.Elaborating on the residual fate of fluxapyroxad and its metabolites based on their nationwide application was vital to protect the human population from their hazardous effects. In this study, a rapid and sensitive analytical method was developed to trace fluxapyroxad and two of its metabolites in peanut matrices using an ultrahigh chromatography method coupled with mass spectrometry (UHPLC–MS/MS) within 3.5 min. The occurrence, pharmacokinetic degradation and terminal magnitudes of fluxapyroxad were reflected in the original deposition of 8.41–38.15 mg/kg, half–lives of 2.5–8.6 d and final concentrations of 0.004–37.38 mg/kg in peanut straw. The total concentrations of fluxapyroxad in peanut straw (0.04–39.28 mg/kg) were significantly higher than those in peanut kernels (<0.001–0.005 mg/kg) and an obvious concentration effect was observed in fresh (0.01–11.56 mg/kg) compared dried peanut straw (0.04–38.97 mg/kg). Fluxapyroxad was demethylated to 3–(difluoromethyl)– N– pyrazole–4–carboxamide, is a novel succinate dehydrogenase inhibitor (SDHI) fungicide, with a high octanol–water partition coefficient (Kow) of 1.35 × 10−3 and a low saturated vapour pressure of 2.7 × 10−6 mPa at 20 °C [Sclerotium rolfsii Sacc. It has been registered in more than 70 crops in China, the European Union (EU), the United States, Japan and Korea, etc. [The peanut is among the most widely commercial oil crops in the world with import values of 92 thousand dollars and export values of 15 thousand dollars in 2021 . However50) of 0.29–0.546 mg a.s./L and to liver tumours developing in rats at 11–82 mg/kg bw/day [N––1H–pyrazole–4–carboxamide (M700F008) and 3–(difluoromethyl)–1–(ß–D–glucopyranosyl)–N––1H–pyrzaole–4–carboxamide (M700F048) [50 of 183–1000 d and 420–731 d [Notably, fluxapyroxad was classified as a Ⅲ grade of toxicological concern with unexpected negative effects on the survival of non-targeted organisms and human health . Fluxapy700F048) , both of700F048) . Evidenc700F048) ,13,14. F20–731 d . The pha20–731 d , which d0), half-life (T1/2) and the concentration variation in large-scale trials across China, for which impossible influencing factors were further discussed. Furthermore, the terminal levels of fluxapyroxad were investigated both in fresh and dried peanut crops in large-scale fields across China. A systematic analysis was conducted between highest residue (HR) of fluxapyroxad and maximum residue limits (MRLs) established internationally providing early warning suggestions for the import and export trade of peanut crops. Finally, the dietary risks for population groups in terms of age, region and gender were evaluated to provide the basic data for scientific use and an effective supervision of fluxapyroxad in peanut crops, providing references for protecting the health of the consumer population from agrochemical exposures.The present study aimed to develop a rapid and effective analytical method to trace fluxapyroxad and its metabolites in peanut kernels and straws; highlighting the fate tendency and dietary risks of the total fluxapyroxad based on its nationwide applications in peanut ecosystems. An analytical method was developed for the simultaneous determination of fluxapyroxad, M700F008 and M700F048 in peanut kernels and straw matrices. Moreover, the occurrence, degradation and the metabolism of fluxapyroxad were elucidated upon with regard to the original deposition (C2) of 0.9967–0.9999 in peanut kernel and 0.9996–0.9999 in peanut straw. The straw samples with high concentrations of the target compounds were diluted uniformly within the linearity range. Significant differences were observed for MEs of fluxapyroxad and metabolites ranging from −30.3% to 10.6% in peanut kernels and ranging from –48.3% to –41.3% in peanut straw, which might be positively related to the organic compounds contained in both the peanut kernels and straw [−7–0.0059 mg/kg, 3.8604 × 10−8–0.0194 mg/kg and 2.0358 × 10−7–0.0005 mg/kg, respectively, which were determined at a signal-to-noise (peak to peak) ratio of three under the above conditions. The LOQ was estimated to be 0.001 mg/kg in the associated matrixes, which was taken as the lowest concentration level with a satisfactory recovery (70–120%) and relative standard deviations (RSDs) of less than 20% , limit of detection (LOD), limit of quantitation (LOQ), repeatability, reproducibility and stability were positively validated based on the analytical quality control criteria of SANTE/11312/2021 . The spend straw , and thend straw ,19. Signthan 20% , providithan 20% . The staYvhua 22 peanut straw , which was 4.5 times over than that of Guihua 17 peanut , demonstrating that peanut cultivar can affect the deposition of fluxapyroxad. The former showed higher straw of 43 cm and full kernel of 81.6 g than the latter cultivar [N–glycosylated to M700F048.The initial concentrations of fluxapyroxad in peanut straw ranged from 8.41 to 38.15 mg/kg, and those were almost undetected in the peanut kernel (<0.001–0.005 mg/kg) after foliage application. The higher concentration of fluxapyroxad was observed in cultivar . The ini1/2 of fluxapyroxad was 2.5–8.6 d in the peanut straw, which was shorter than that of the apple with 9.4–12.6 d [1/2 of fluxapyroxad was observed in Trial #10 , and the longest one was observed in Trial #9 . Therefore, the high temperature and rainfall promoted the pharmacokinetic degradation of fluxapyroxad in peanut crops. The concentration of M700F048 in peanut straw was 0.02–8.62 mg/kg during peanut cultivation, which was up to 14.4 times more than that of M700F008 (0.01–4.12 mg/kg), demonstrating that N–glycosylation was the main metabolized process of fluxapyroxad in the peanut straw. The maximal concentration of M700F048 was found in Trial #9 , whereas that of M700F008 was observed in Trial #5 . The concentration variations of the metabolites were consistent with those of the parent.Moreover, the pharmacokinetic degradation of fluxapyroxad conformed to pseudo–first–order kinetics well with the determination coefficient (r) of 0.7819–0.9936. The T4–12.6 d . The shoN–glycosylation was the main metabolized process in the peanut straw. Typical UHPLC–MS/MS (MRM) chromatograms of fluxapyroxad, M700F008 and M700F048 are shown in The terminal concentrations of fluxapyroxad were 0.004–37.38 mg/kg in the peanut straw, accounting for 0.2–64.4% of the original concentration. The relatively low levels were observed in the peanut kernel with <0.001–0.002 mg/kg. The study for fluxapyroxad in wheat cultivation systems further confirmed the result, where the concentration of fluxapyroxad in wheat straw (0.31 mg/kg) was significantly higher than that in wheat grain (<0.01 mg/kg) . The conLuhua 14 peanut of 3.64–39.28 mg/kg, whereas the minimum was in Guihua 17 peanut with 0.04–0.35 mg/kg, and the terminal concentrations of fluxapyroxad in Baisha 1016 peanut were significantly different in Trial #9 (10.22–18.01 mg/kg) and Trial #8 (1.26–1.85 mg/kg). The specific mechanism and possible factors synergistically influencing the residual fate of fluxapyroxad require further investigation in follow–up studies.The total concentrations of fluxapyroxad, M700F008 and M700F048 were further investigated by factors of 0.72–1.039, ranging from <0.001 to 0.005 mg/kg in the peanut kernel and between 0.04–39.28 mg/kg in the peanut straw . The STMThe MRL values of fluxapyroxad was 0.01 mg/kg in the peanut kernels in China, which were consistent with the values of Codex Alimentarius Commission (CAC) , AmericaTo assess acute dietary exposure of the total fluxapyroxad through peanut kernel consumption, the ARfD% of the total fluxapyroxad was estimated for different populations, including children (1–11 years old), general population (>11 years old) and childbearing women (14–45 years old) A. The ac−3 mg/kg bw [p < 0.01 at a 95% probability, which was consistent with the exposure of ethirimol in peanuts [The chronic dietary risk quotient of fluxapyroxad was also calculated in registered crops with 0.415–1.350%. The minimal ADI% of the total fluxapyroxad was observed in peanut kernels with 0.007–0.023% for the association population B, accounmg/kg bw , with tomg/kg bw ,29. More4) were purchased from Beijing Chemical Company . Ultrapure water was prepared from a Milli–Q system . Octadecylsilane  and graphitized carbon black  were provided by Agela Technologies . Fluxapyroxad standard (purity 99.99%), M700F008 standard (purity 99.5%), and M700F048 standard (purity 94%) were purchased from Dr. Ehrenstorfer . The formulation product 167 g/L of the fluxapyroxad suspension concentrate (SC) was provided by J&K Scientific . Formic acid (FA) of chromatographic grade and acetonitrile  were obtained from Sigma–Aldrich . Analytical grade MeCN (99.8% purity), acetic acid (AcOH), sodium chloride (NaCl) and anhydrous magnesium sulfate  for the peanut crops. The application frequency and interval of pesticides were 2 and 7 d, respectively, according to the good agricultural practices (GAPs) recommendations. The pharmacokinetic dissipation study was conducted in Trial #2, Trial #5, Trial #9 and Trial #10, which have typical peanut varieties and distinct climate conditions across China. The geographic information, hydrological characteristics, climate factors, soil characteristic and radish cultivars are summarized in Ten cultivation origins of peanut crops were selected from the main producing provinces or municipalities of China spanning five climate zones, which had no history of fluxapyroxad in the past three years. Based on the Organization for Economic Co-operation and Development Guidelines (OECD) for the Testing of chemicals No. 509 Crop Field Trial , three tRepresentative peanut samples were obtained from each plot, excluding the edges and ends of the plots, preferably with intact rinds and disease-free. Both the peanut kernel and straw samples were collected at increasing intervals on 2 h, 7 d, 14 d, 21 d and 28 d after application for the dissipation investigation. For the terminal level study of fluxapyroxad, the samples of mature peanut grains and straws were collected at preharvest intervals (PHIs) of 14 and 21 d after the last application in accordance with FAO/WHO recommendations. Each of the kernel and straw samples were not less than 1 kg and were shipped to the laboratory within 8 h. Exterior impurities were removed, chopped into quarters within 1 cm, divided into 150 g subsamples and kept frozen at −20 °C.−1. Subsequently, 3 g of NaCl were added and the mixture was repeatedly vortexed for 5 min, followed by centrifugation for 5 min with a Frontier FC5706 centrifuge  at 1107× g relative centrifugal force (RCF). Additionally, 1.5 mL of the supernatant was transferred into a single-use centrifuge tube, which contained 50 mg C18 and 150 mg anhydrous MgSO4 for the peanut kernel and 50 mg C18, 10mg GCB and 150 mg anhydrous MgSO4 for the peanut straw. The vortex step was repeated for 30 s and centrifuged for 1 min with a Heraeus Pico 17 Centrifuge  at 2188× g relative centrifugal force. The resulting supernatant was withdrawn, reconstituted by the initial mobile phase, and filtered through a 0.22 μm nylon syringe filter into an autosampler vial for UHPLC–MS/MS injection.Representative homogenized samples (5 ± 0.01g) of peanut kernel and straw were weighed into 50 mL polytetrafluoroethylene centrifuge tubes. Five mL of 1.2% AcOH–MeCN and equivalent volumes of ultrapure water were added to the peanut kernel and additional 5 mL solutions were required for the peanut straw. Then the mixture was shaken for 5 min using a CK–2000 high-throughput grinder  at an oscillation frequency of 1350 min2, and the collision gas was Ar with 2 × 10−3 mbar in the T-wave cell. Cone and desolvation flows of 50 and 650 L/h were applied, respectively. The multiple reactions monitoring (MRM) transitions m/z 381.3→131.1 and m/z 381.3→248.1 were used for the quantification and confirmation of fluxapyroxad with the collision energy of 26 and 22 eV, whereas they were m/z 366.0→306.0 (20 eV) and 366.0→326.0 (16 eV); and m/z 528.1→326.1 (28 eV) and m/z 528.1→346.0 (20 eV) for M700F008 and M700F048, respectively. The cone voltage of the fluxapyroxad, M700F008 and M700F048 was set at 50, 30 and 56 V, respectively, and the dwell times were 0.034 s. An Ultra–performance Liquid Chromatography–Triple Quadrupole Tandem Mass Spectrometry (Waters ACQUITY UPLC H–Class/Xevo TQD) equipped with a Waters ACQUITY HSS T3 column  was employed to separate the fluxapyroxad and main metabolites simultaneously. Gradient elution was initialized by 10/90 volume of MeCN (solvent A) and 0.05% FA in water (solvent B) for 0.5 min, and then increased from 10% to 90% A over 2.0 min, held at 90% A for 0.1 min, and then equilibrated by 10% A for 0.9 min, providing a total analysis time of 3.5 min. The flow rate, column temperature and the injection volume were set at 0.45 mL/min, 40 °C, and 5 µL, respectively. A high sensitivity for fluxapyroxad was optimized under a negative mode with a 1.5 kV capillary voltage, 150 °C source temperature and 350 °C desolvation temperature. The nebulizer gas was NmS and sS are the slopes of the calibration curves obtained in the matrix and in the solvent, respectively. ME ≤ −10% (MeCN as the reference) indicates a significant matrix suppression effect, whereas ME ≥ 10% indicates a significant matrix enhancement effect. ME is not significant with −10% < ME < 10% and does not exist at a value of zero [1/2) can be calculated . The possible first-order kinetic model is as follows [0 and Ct represent the initial sample concentration (mg/kg) and residue concentration (mg/kg) at time t (d). The T1/2 was calculated using Hoskins’ Formula (3):The matrix effect (ME) refers to the variation in ionization efficiency of the target compounds with the presence of co-effluents, which were evaluated using Equation (1): of zero . The dis follows : (2)Ct=CThe starting point of the regressive function is the maximum value of the concentrations and decreases in the following days. The deterministic model is a popular approach for a dietary risk assessment. It is used widely because it requires minimal resources and data to calculate, and it is fairly easy to understand. Additionally, the deterministic model of acute dietary risk is based on the Food and Agriculture Organization of the United Nations (FAO) classification guidelines, there were four different models for the calculation of the national estimated short–term intake of pesticides (NESTI) , Formulat-test and the one-way Analysis of Variance (ANOVA) with Duncan’s post-hoc test using SPSS 22.0 . The different tests for nonnormally distributed datasets were accessed by the Kruskal–Wallis one–way ANOVA test. Differences at p < 0.05 were considered statistically significant for both Tukey’s HSD test and Student’s t-test in this study.The differences in data sets that were normally distributed were assessed by the N–glycosylated M700F048. The higher concentrations of the total fluxapyroxad were observed in the peanut straw as opposed to the kernel, especially in dried straw with concentrations of up to 38.97 mg/kg. The acute risks of the total fluxapyroxad were of 0.006–0.012%, whereas the chronic risks were from 0.415% to 1.289% for human population. Despite the acceptable exposure risks, the potential health hazards of fluxapyroxad should be continuously emphasized, given its increasing applications.A rapid and sensitive tracing methodology was developed for fluxapyroxad, M700F008 and M700F048 in peanut matrices by UHPLC–MS/MS, with an LOQ of 0.001 mg/kg and retention times of 2.11–2.55 min. The occurrence, dissipation and concentration variations of fluxapyroxad were further elucidated in peanut crops, as reflected by the original deposition, half-lives and terminal levels. Fluxapyroxad was metabolized to M700F008 in peanut crops, which can be the precursor of


This study characterised the decoupling of internal-to-external workload in marathon running and investigated whether decoupling magnitude and onset could improve predictions of marathon performance.The decoupling of internal-to-external workload was calculated in 82,303 marathon runners . Internal workload was determined as a percentage of maximum heart rate, and external workload as speed relative to estimated critical speed (CS). Decoupling magnitude  was classified as low (< 1.1), moderate (≥ 1.1 but < 1.2) or high (≥ 1.2). Decoupling onset was calculated when decoupling exceeded 1.025.p < 0.01). Compared to females, males’ decoupling magnitude was greater  and occurred earlier . Marathon performance was associated with the magnitude and onset of decoupling, and when included in marathon performance models utilising CS and the curvature constant, prediction error was reduced from 6.45 to 5.16%.The overall internal-to-external workload decoupling experienced was 1.16 ± 0.22, first detected 25.2 ± 9.9 km into marathon running. The low decoupling group (34.5% of runners) completed the marathon at a faster relative speed (88 ± 6% CS), had better marathon performance (217.3 ± 33.1 min), and first experienced decoupling later in the marathon (33.4 ± 9.0 km) compared to those in the moderate , and high decoupling groups (32.8% runners, 82 ± 7% CS, 238.5 ± 30.7 min, and 19.1 ± 6.8 km; all Durability characteristics, assessed as internal-to-external workload ratio, show considerable inter-individual variability, and both its magnitude and onset are associated with marathon performance. Marathon running has been the subject of considerable interest in recent years, and it is generally accepted that multiple factors can affect its performance –4. For eentclass1pt{minimamarathon , 6. Combmarathon –10. It imarathon . Indeed,marathon , 12. Sinmarathon , 13, 14,marathon , 16.An interesting finding from studies investigating the ability of CS to predict marathon performance , 16 was The aims of this study, therefore, were to (i) characterise the decoupling of internal-to-external workload during a marathon in a large cohort of recreational runners; and (ii) investigate whether the magnitude and time of onset of the decoupling could predict marathon performance, and whether taking into consideration the decoupling improved predictions derived from CS alone. Furthermore, given recent reports highlighting the differences in fatigability between males and females , which m®  under limited research license. The dataset contained anonymised data and, therefore, the ethics boards of all institutions  deemed the study exempt from ethical approval. Athletes uploaded the data from training sessions, collected through smartphones or other devices , into the running platform. The dataset consisted of time, location, distance, and elevation data sampled at 100 m intervals. In addition, heart rate (HR) was available from all training sessions. HR data was processed in a similar way to running data, and thus averaged at 100 m intervals. The characteristics of the dataset used in the current study are provided in Table A large dataset of recreational runners was made available to the authors by the running platform StravaD′, the curvature constant of the speed-duration relationship that represents running capacity above CS, were estimated from raw training data, as previously described [D′ [Critical speed and escribed . In brieescribed , 22. Theescribed . For eacibed [D′ .max). The HRmax for the cohort was given as 178 ± 18 beats per min (bpm) and 187 ± 8 bpm using an age-predicted calculation [max was defined as the highest HR recorded in any training session for each runner. The external workload was determined as the speed, relative to CS, during the recorded marathon. The first (0–5 km) and last (40–42.2 km) segments of the race were excluded to avoid possible artefacts caused by sudden changes in pace in the first and last few kms of the race, respectively. The decoupling observed in the last 5 km segment of the race (35–40 km) was used to determine the overall magnitude of the decoupling experienced by each athlete, and expressed relative to the 5–10 km segment. Thus, a decoupling of 1.15 indicates that internal-to-external ratio (ratio between %HRmax and %CS) was 15% greater in the 35–40 km segment compared to that observed in the 5–10 km segment of the race. To estimate the onset of decoupling, the race segment from which decoupling remained consistently  above 1.025 was calculated for each athlete, focusing on the race segments from 10 to 40 km. We converted this race segment into an estimated distance by calculating the mid-point of the segment. Thus, if a decoupling > 1.025 was first detected in the 20–25 km segment of the marathon and sustained to the 35–40 km segment, then the onset was assumed to be at 22.5 km. The distance at which decoupling was first observed was converted to time of onset using average running speed. If a decoupling > 1.025 was not detected at all for a runner, the onset was assumed to be their either 42.2 km or their finish-time, as appropriate, to represent a runner completing the marathon without decoupling.Each marathon was divided into eight 5-km segments plus the final 2 km of the race, and the decoupling of internal-to-external workload ratio was calculated for each segment. The internal workload was determined as a percentage of maximum HR  were compared with a Welch's t-test , and significance was accepted at p < 0.01. Cohen’s d was used as a measure of effect-size, and interpreted as very small (0.01), small (0.20), medium (0.50), large (0.80), very large (1.20) and huge (2.00) [Athletes experiencing a decoupling < 1.1 in the last segment of the race were classified as low decoupling, a decoupling ≥ 1.1 but < 1.2 was considered as moderate, and if the decoupling was ≥ 1.2 it was deemed as high decoupling . In ordee (2.00) . Results−1, and thus marathon time was ~ 3 h and 47 min ± 33 min. The CS and D′, estimated from raw training data corresponded to 3.72 ± 0.48 m·s−1 and 196 ± 90 m, respectively, and therefore the average marathon speed corresponded to 85 ± 7% of CS. Male runners had ~ 10% superior marathon performance and CS compared to female runners (both p < 0.01), but females were able to complete the marathon at speeds closer to their CS .The overall marathon performance and decoupling characteristics of the athletes within the dataset are presented in Table The average decoupling experienced in the 35–40 km segment was 1.16 ± 0.22. However, there was considerable inter-individual variation. Out of 82,303 runners, 34.5%  exhibited low decoupling (decoupling < 1.1 in the 35–40 km segment), 32.7%  moderate decoupling (≥ 1.1 but < 1.2), and 32.8%  were classified as high decoupling (≥ 1.2). The time-course of decoupling for the low, moderate, and high decoupling groups over the course of a marathon is shown in Fig. p < 0.01, d = 0.22). Male runners were relatively evenly distributed in the low, moderate and high decoupling groups , whereas their female counterparts were more frequently classified as low and moderate decoupling compared to high decoupling .The overall magnitude of decoupling was greater for males compared to female runners . This held true for all decoupling groups  and faster marathon time , and had faster marathon times  and absolute marathon performance (marathon finish time) exhibited a strong association with the magnitude of the decoupling. Athletes exhibiting lower decoupling magnitude completed the marathon at a higher percentage of CS , prediction error falls to 5.16%, which represents an overall improvement of 20.00% compared to the model using CS and D′ only. Overall, the prediction error was lower for female athletes (p < 0.01), irrespective of the model used  reduced the prediction error by 20%. Female runners exhibited a better durability profile, as the decoupling exhibited lower magnitude and later onset than that observed in male runners. These findings suggest that durability characteristics, such as its magnitude and onset, should be taking into consideration in marathon running because both parameters were associated with marathon performance. Moreover, the results from this study indicate that female runners experience less decoupling than their male counterparts.The primary aim of the present study was to explore the durability characteristics of a large, heterogenous group of recreational runners by calculating the decoupling of internal-to-external workload ratio during marathon running. In addition, we investigated whether the overall magnitude and onset of decoupling experienced by runners contributed to marathon performance, and whether these results were different in male and female runners. The main findings were that athletes experienced a ~ 1.16 (~ 16%) decoupling between HR and speed in marathon running, which started after 25.2 ± 9.9 km. However, there was large inter-individual variability, and runners could be classified into low, moderate and high decoupling groups. We found that runners in the low decoupling group completed the race at a higher percentage of their CS, with a faster overall time, and had a later onset of decoupling. Moreover, whilst CS and The large sample of recreational marathon runners analysed in the current study experienced internal-to-external workload decoupling of ~ 1.16, which indicates that the ratio between internal workload (HR) and external workload  increased by ~ 16% throughout a marathon. However, there was considerable inter-individual variability in the magnitude of decoupling. Athletes were classified, based on the magnitude of the decoupling observed in the last 5 km segment of the marathon, as low, moderate and high decoupling, as previously suggested . DespiteD′ and the attainment of D′, but the intensity of exercise must remain below CS [Prolonged exercise, such as marathon running, necessitates a physiological steady state, and thus is typically performed at intensities close to, but below, CS , 16. Exeterwards , 28. Altbelow CS . Previoubelow CS , CS [17,below CS  and endubelow CS  decreasePrevious studies have shown that CS is a strong predictor of marathon performance, with elite marathon runners’ best performances completed at 96% CS , and fasThe onset of decoupling was estimated to occur when a decoupling of at least 1.025 was first detected. This is, again, an arbitrary threshold representing a 2.5% increase in internal-to-external workload ratio. However, we found that this approach of detecting the onset of decoupling was also associated with marathon performance Fig. . AthleteD′. The addition of durability traits to this model, namely its magnitude and onset, reduced the prediction error to 5.16%, a 20% improvement in accuracy. Therefore, the data presented in the current study support that models aiming to predict marathon performance, and more generally models of endurance performance, should take into consideration the durability of physiological traits.Critical speed denotes the highest sustainable oxidative metabolic rate, and thus is strongly associated with endurance performance. Indeed, previous studies have shown that marathon performance can be predicted with ~ 7% error using models derived from CS . SimilarThere are several factors that can explain the decoupling of internal-to-external workload decoupling. The mechanisms explaining the inter-individual variability in durability characteristics may be related to skeletal muscle fibre type characteristics given type I fibres are more resilient to exercise-induced loss of mechanical efficiency . Therefo2 cost of running has been shown to increase concomitantly over increased distances [Further to purely physiological mechanisms, it could be postulated that runners with greater durability are able to preserve a more economical pattern of running throughout the marathon. The greatest sustainable running speed is strongly mediated by running economy . Howistances . Elevateistances . Consequistances , kineticistances , as wellistances , 40. Res runners . FurtherDecoupling was quantified as the internal-to-external ratio , and theent}V˙O2  or HR [4ent}V˙O2  during pent}V˙O2  for a reThe results of the present study demonstrate that females displayed a lower magnitude and later onset of decoupling than males Fig. , Table 1 females . The dat females , 47, hav females , and may females , and pro females , 47. ComFor this study, we relied on a large dataset of recreational runners. Using such a large dataset allowed the exploration of decoupling characteristics during the marathon, and offers an insight as to whether the internal-to-external workload experienced during prolonged exercise contributes to explain marathon performance. However, when utilising this approach to use raw training data to calculate CS, it was not possible to verify if participants have performed a maximal effort, for example, checking whether e trials . Nonethee trials . Data wae trials . Future e trials , 12. Howe trials , and is e trials , 13. FurTo quantify internal workload, we used HR data, and it should be acknowledged that HR is likely to exhibit somewhat different kinetics to that of exercise , 51. Mor}V˙O2max ). Enviro}V˙O2max . A questD′. Females had, overall, a better durability profile, as they exhibited lower decoupling in internal-to-external ratio. The data presented herein, therefore, suggest that appreciation of inter-individual differences in athlete durability may help improve understanding of an individual athlete’s performance capabilities in marathon running.The internal-to-external ratio during a marathon was ~ 1.16, which represents a 16% increase in internal-to-external ratio over the course of the marathon, and was first detected ~ 25 km into the marathon. However, there was a large inter-individual variation in both the absolute magnitude of the decoupling and its onset. Importantly, both decoupling magnitude and onset were associated with performance, and the inclusion of these durability traits increased the precision of models of marathon performance by ~ 20% compared to those relying exclusively on CS and


Fabry disease (FD) is an X-linked inherited disease where renal complications are associated with a poor prognosis. However, little is known about the prevalence of Fabry nephropathy (FN) in patients with chronic kidney disease (CKD). We extracted FN data from the Japan Renal Biopsy Registry, analyzed the prevalence of FN, and examined the correlation between clinical characteristics and renal involvement according to sex differences and hemi- and heterozygosity in patients with FD.A total of 38,351 participants who underwent renal biopsy were retrospectively enrolled, and FN was determined. The clinical characteristics of FD patients were examined based on sex differences.2, respectively. Mean systolic blood pressure (SBP) was 126.4 ± 17.1 mmHg and diastolic blood pressure was 76.1 ± 12.6 mmHg. An inverse correlation between eGFR and logarithm UP levels was observed , SBP was positively associated with logarithm UP  overall and inversely associated with eGFR  regardless of sex, and SBP was an independent determinant of proteinuria (p = 0.004) and eGFR (p = 0.007).Twenty-nine patients (0.076%)  were diagnosed with FN. Median estimated urinary protein (UP) and mean eGFR levels were 0.9 [interquartile range (IQR) [0.7–1.6] g/gCr and 67.1 ± 36.8 mL/min/1.73 mThe prevalence of biopsy-proven FN was 0.076%. Since SBP is associated with eGFR regardless of zygosity, strict SBP control might be necessary to prevent progression to end-stage kidney disease in both male and female patients with FN.The online version contains supplementary material available at 10.1007/s10157-022-02287-w. Fabry disease (FD) is an inborn metabolic error caused by a deficiency of alpha-galactosidase A (GLA), a lysosomal hydrolytic enzyme that is inherited in an X-linked manner , 2. The The prevalence of FD in Europe and the United States was initially reported to be approximately 1/40,000, but a screening test of newborn infants showed that the number of boys with low GLA activity was approximately 1/3100 in Italy . In JapaTo date, FD screening for evaluating the prevalence of Fabry nephropathy (FN) in male patients with CKD is measured by GLA activity; however, due to the lack of a precise diagnosis of FN, other kidney diseases might coexist in FD patients with renal involvement. Furthermore, female patients are not suitable for screening due to residual GLA activity. Therefore, renal biopsy is necessary to examine the precise prevalence of FN in male and female patients with CKD. In this study, we investigated the prevalence of renal biopsy-proven FN in patients with CKD registered in the Japan Renal Biopsy Registry (J-RBR), organized by the Japanese Society of Nephrology. Further, we evaluated the clinical characteristics of FN according to sex differences (hemizygous and heterozygous).Of a total of 38,351 registered patients who underwent renal biopsy between July 2007 and January 2018 in the J-RBR, 172 patients with undescribed clinical diagnoses were excluded, and the remaining 38,179 patients were included in this study : Sex male = 2, female = 1 , 14.For Ht = height (m), sCr = serum creatinine .t test. All statistical analyses were performed using the JMP Pro ver. 15 software . Statistical significance was set at P < 0.05.Results are presented as the median or mean ± standard deviation. To perform linear regression analysis, UP was log-transformed after adding 0.1. Univariate regression analysis was performed to determine the correlations between eGFR and proteinuria, proteinuria and SBP, and eGFR and SBP. Multiple regression analysis was performed to assess independent determinants of eGFR and proteinuria. Differences between the groups were assessed using the chi-squared test or unpaired Of the 38,179 enrolled patients with CKD, 32 (0.084%) were classified as patients with FD who were not treated with enzyme replacement therapy (ERT). Three participants with FD were excluded because they had undergone renal transplantation or hemodialysis. Finally, 29 cases were analyzed, and the prevalence of FN was 0.076%, equivalent to 7.6 patients per 10,000 kidney biopsies  in all patients. Mean eGFR was 67.1 ± 36.8 mL/min/1.73 m2, and median estimated proteinuria was 0.9 [IQR 0.7–1.6] g/gCr. A total of 56% of patients (14 out of 25) and 13.6% of patients (three out of 22) were prescribed antihypertensive drugs and had a history of diabetes, respectively , G2: n = 3 (16%), G3a: n = 1 (5%), G3b: n = 5 (26%), G4: n = 2 (11%), G5: n = 1 (5%), and unclassifiable: n = 3 (16%) in men and G1: n = 1 (10%), G2: n = 7 (70%), G3a: n = 0 (0%), G3b: n = 0 (0%), G4: n = 1 (10%), and unclassifiable: n = 1 (10%) in women  and 0.7 [IQR 0.7–0.8] g/gCr for females (n = 9), with no significant difference (p = 0.89)  and 67.6 ± 20.7 mL/min/1.73 m2 for females (n = 10), with no significant difference (p = 0.95) (Table p = 0.67) , and mean DBP was significantly higher in males compared with that in females   Table a. Mean en = 23, r2 = 0.23, p = 0.02); however, no correlation by gender   and male  FN patients, however, not in females , males , and females  was observed  (Table p = 0.016) and eGFR was lower  in antihypertensive drugs users than those in nonusers   Fig. a. SystolNephropathy is a major complication in patients with FD, which exacerbates the quality of life and life expectancy. Therefore, screening for FN in patients with CKD is valuable not only for evaluating the prevalence of this disease but also for implementing early exposure to ERT or chaperone therapy to inhibit progression to ESKD. In this retrospective study, we report, for the first time, that the prevalence of biopsy-proven FN in patients with CKD is 0.076%. To date, the prevalence of FD in male patients with CKD has been reported to be 0.48% , which i2 were outliers with respect to eGFR, which may affect the mean eGFR for males. Furthermore, it is speculated that different mutation types, such as classical and late-onset gene mutations, might affect these results. Classical mutations in FD accelerate the development of multiple organ damage in young patients, whereas FN with late-onset gene mutations becomes prevalent in elderly patients with both hemi-and heterozygous mutations. In our study, four male patients diagnosed with FN were over 60 years of age, suggesting that they might have the late-onset FD gene mutation. Since there was no information regarding the gene mutation in J-RBR, further verification is needed to clarify this issue. In addition, some patients were positive for hematuria, and the rate of hematuria was higher in FN patients with heterozygous gene mutations than in those with hemizygote mutations. Hematuria is not a specific characteristic feature of FN; therefore, some comorbidities, such as urinary tract infection, menstruation, or both, might result in hematuria. Furthermore, three FN patients were negative for proteinuria (UP/UCrea < 0.15 g/gCr) with normal renal function (eGFR > 60 mL/min/1.73 m2) at the time of renal biopsy. A family history of FD, existence of other organ damage, or both, such as cardiac myopathy related to FD, may have been the reason for renal biopsy. Since it has been reported that albuminuria is found only in 55% of male and 35% of female FN patients with an eGFR of 60 mL/min/1.73 m2 or higher [The sex difference, in other words, hemizygous and heterozygous mutations, might affect the development of FN. However, in this study, there was no sex-related difference in age, proteinuria, or eGFR levels at the time of renal biopsy. Small sample size with a non-normal distribution of these factors might affect the results. Indeed, the median age was 36 years for males and 44 years for females. Further, 58% 11/19) of the males and 30% (3/10) of the females were under 40 years of age. Thus, it is possible that males are younger than females in this study population; two males over 120 mL/min/1.73 m of the mAccumulation of Gb3 in enlarged podocytes is a feature of FN, which impairs podocyte function and accelerates proteinuria, followed by detachment from the glomerular basement membrane, leading to ESKD . Ortiz eThe present study had some limitations: First, the small sample size was insufficient for analysis and rendered it difficult to draw definite conclusions from this study. Second, data on genetic information, symptoms, information on urinary mulberry body, and family history are not available in J-RBR. Third, drug-induced lysosomal disorders cannot be ruled out. Therefore, large numbers of FN patients diagnosed with renal biopsy and genetic analysis with detailed information are needed to clarify which clinical and pathological characteristics are correlated with progression of FN in future.In conclusion, the prevalence of biopsy-proven FN is 0.076% in Japan. Since SBP is associated with eGFR and proteinuria regardless of sex, strict SBP control might be necessary to prevent the progression to ESKD in both male and female patients with FN.Supplementary file1 (DOCX 37 KB)Below is the link to the electronic supplementary material.


To report the efficacy and safety of brolucizumab in the treatment of refractory serous pigment epithelial detachment (PED) secondary to polypoidal choroidal vasculopathy (PCV).Twenty-six eyes of 26 patients were included. Intravitreal brolucizumab 6.0 mg was administered, followed by pro re nata (PRN) retreatment at monthly follow-ups. All patients underwent spectralis domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography before the first brolucizumab injection. SD-OCT was repeated at follow-up visits. The height and width of the serous PEDs, measured using SD-OCT, were analyzed.p < 0.05). However, the visual outcome did not improve significantly (p > 0.05). A good response was achieved in 69.2% of eyes at 1 month and at the last visit. Relapse and complete resolution were observed in 27.8 and 23.1% of patients, respectively. The number of brolucizumab injections was 2.00 ± 0.85. Intraocular inflammation, vascular obstruction, and retinal pigment epithelial tears were not observed.The number of previous anti-VEGF injections was 12.3 ± 15.0. During brolucizumab treatment, anatomical improvement was achieved and maintained in the height and width of the PEDs (Intravitreal brolucizumab may be an effective and safe treatment option for refractory serous PEDs in patients with PCV. Polypoidal choroidal vasculopathy (PCV) is a subtype of neovascular age-related macular degeneration (AMD) . It is cRetinal PEDs are important predictors of vision loss in patients with AMD . RetinalThe responsiveness of retinal PEDs in n-AMD to anti-VEGF treatment has been reported in previous studies –17. RespThe recently developed anti-VEGF agent, brolucizumab , is a new humanized single-chain variable fragment that shows better tissue penetration and longer durability than previous anti-VEGF agents . Its potThe purpose of this study was to investigate the efficacy and safety of brolucizumab for serous PEDs refractory to bevacizumab, ranibizumab, and/or aflibercept in patients with PCV.This study was approved by the Institutional Review Board (IRB) of Samsung Medical Center and adhered to the tenets of the Declaration of Helsinki. Given the retrospective design of this study and the use of anonymized data, requirements for informed consent were waived by the IRB of Samsung Medical Center.We performed a retrospective medical record review of consecutive patients diagnosed with PCV aged over 50 between April 2021 and April 2022 at the Hangil Eye Hospital and Samsung Medical Center. Patients were included if they had serous PEDs secondary to PCV, showed unresponsiveness to other intravitreal anti-VEGF drugs , underwent brolucizumab injections and underwent more than 3 months of follow-up after the first brolucizumab injection. If the height of serous PED did not decrease to less than 200 μm in previous anti-VEGF treatments, it was defined as unresponsiveness.The exclusion criteria were uveitis, severe diabetic retinopathy, severe hypertensive retinopathy, severe epiretinal membrane, retinal detachment, glaucoma, refractive error exceeding ± 6 diopters, history of retinal laser photocoagulation, severe ocular media opacity, and insufficient ocular examinations. Demographic information including age, sex, previous anti-VEGF injections, and comorbidities was obtained for each patient.PCV was diagnosed according to the CONAN (Consensus on Neovascular Age-related macular degeneration Nomenclature) study group . OCT, flIntravitreal brolucizumab 6.0 mg was administered, followed by pro re nata (PRN) retreatment at monthly follow-ups. The first follow-up was performed 1 month after the first treatment. PRN retreatment decision was made by the presence of IRF and SRF or increased size of serous PED in OCT images at each follow-up visit. All enrolled patients underwent a comprehensive ophthalmologic evaluation before the first brolucizumab injection. These included measurements of the BCVA, spectral domain optical coherence tomography , FA, and ICGA. The BCVA and SD-OCT were repeated to assess responses.The OCT images were obtained using Spectralis HRA + OCT , which combines the advantages of confocal scanning laser ophthalmoscopy (cSLO) and SD-OCT to facilitate point-to-point registration analysis. The protocol of SD-OCT consisted of two B-scans centered on the fovea  and raster scans . Automatic real-time (ART) mode using an eye-tracker system was activated. During the OCT examination, the patients were continuously encouraged to fixate on the internal fixation target. FA and ICGA were performed with simultaneous OCT scans with a maximum density (11 μm distance between the adjacent B-scans) and averaging (100 frames for one B-scan image). Central macular thickness (CMT) was measured at the circular area 1 mm centered to the fovea, acquired from 3D scan protocol, given by the automated software of SD-OCT.Serous PED was identified by a homogeneous hyporeflective subRPE space in the SD-OCT image. If there were more than one serous PED, the highest PED was analyzed. The location of serous PED was classified into subfoveal and extrafoveal lesion. The fovea was defined as the maximum depression and its surrounding area, the diameter of 500 μm.The height and width of the PEDs were manually measured in a horizontal raster scan image of the highest PED using a caliper tool available on SD-OCT devices. The PED response after treatment was defined as following: “Good response” defined as a decrease in PED height ≥ 50% from baseline; “Partial response” defined as a decrease in PED height < 50% from baseline, and “Poor response” defined as an increase in PED height more than baseline. “Relapse” was defined as a more than two times increase in PED height at any time since showing good response at 1 month. “Complete resolution” was defined as a completely flattened PED without empty space between the RPE and Bruch’s membrane at any time.All measurements were assessed by two independent retinal specialists (S.W.N. and M.K.). Inter- and intragrader agreement on each measurement was regularly assessed, and consensus training was initiated when κ values were below 0.6. All uncertain diagnoses were adjudicated by a senior interpreter (D-I.H.).p-value of < 0.05. All statistical analyses were performed using SPSS software .Quantitative variables are presented as mean ± standard deviation. Frequencies were compared between groups using the chi-square or Fisher’s exact test. Analyses of continuous variable changes were performed using independent t-tests. Statistical significance was defined as a Twenty-six eyes of 26 patients with refractory serous PEDs in PCV were enrolled in this study. The mean age of the population was 69.0 ± 7.6 years. The mean baseline BCVA was 0.31 ± 0.28 logMAR, mean PED height at baseline was 485.6 ± 179.2 μm, and mean PED width at baseline was 2672.8 ± 1129.6 μm. All eyes had previously received anti-VEGF injections. One eye was treated with photodynamic therapy. Table p = 0.000), and 172.4 ± 183.7 μm (p = 0.000) at the last visit. The PED width decreased significantly during the study period. The mean PED width decreased from 2672.8 ± 1129.6 μm at baseline to 1907.4 ± 1480.9 μm at 1 month (p = 0.041), and 1821.0 ± 1497.8 μm at the last visit (p = 0.025). Whereas the BCVA (logMAR) showed a continuous reduction during the follow-up period, it did not improve significantly (p > 0.05). The BCVA (logMAR) was changed from 0.31 ± 0.28 logMAR at baseline to 0.24 ± 0.27 logMAR at 1 month (p = 0.320) and 0.19 ± 0.16 logMAR at the last visit (p = 0.061)  at 1 month and at the last visit. The percentage of partial PED response was 23.1% (6 eyes) at 1 month and at the last visit. The percentage of patients with a poor PED response was 7.7% (2 eyes) at 1 month and at the last visit. The patients who showed a good response at 1 month mostly presented with a good response at the last visit (83.3% (15/18)). The patients who showed a partial response at 1 month presented with a 50.0% (3/6) of good responses at the last visit. All patients with a poor response at 1 month presented with a poor response at the last visit (100.0% (2/2)).p = 0.107).Relapse was observed in 27.8% (5/18) of the patients who showed a good response at 1 month. Among them, 60.0% (3/5) showed a good response at the last visit, and 40.0% (2/5) showed a partial response at the last visit. Complete resolution was achieved in 23.1% (6/26) of the patients. The mean time and number of brolucizumab injections to achieve complete resolution were 1.50 ± 0.84 [1.00–3.00] months and 1.17 ± 0.41 [1.00–2.00] injections, respectively. The BCVA change between complete resolution and baseline was − 0.18 ± 0.19 logMAR. Visual improvement was observed in all patients in a complete response group without statistical significance (p = 0.000).The development of RPE tears, intraocular inflammation (IOI), retinal vasculitis, and vascular obstruction was not observed. CMT decreased from 515.5 ± 235.7 μm at baseline to 285.9 ± 103.1 μm at the last visit , subretinal fluid (SRF), and/or PED . PED canp < 0.05) and were maintained at the last visit (p < 0.05). However, the BCVA did not improve significantly at 1 month (p > 0.05) or at the last visit (p > 0.05). Although the BCVA improvement was not statistically significant, visual improvement was observed in this study. This seems to be due to the lack of visual improvement in general, although some patients showed improved vision. Longer follow-up durations and large-scale studies are necessary to reveal the relationship between functional outcomes  and brolucizumab treatment.PED treatment should be considered in cases with increasing PED size and associated vision loss . In thisIn this study, brolucizumab showed significant response rates to the PED height. The response at 1 month after brolucizumab treatment is important to predict the prognosis. A previous study of exudative AMD reported that the PED height was significantly reduced within 1 month after the first brolucizumab injection . It is sRelapse was observed in 27.8% (5/18) of patients in this study. Among them, 60.0% (3/5) showed a good response at the last visit, and 40.0% (2/5) showed a partial response at the last visit. These results indicate that PED relapse can be properly managed with repeated brolucizumab injections. Moreover, patients with refractory PED secondary to PCV should be followed-up with thorough examination after brolucizumab injections because of the possibility of relapse.p > 0.05). Cho et al. also reported that complete resolution of PED with anti-VEGF treatment was related to visual improvement [Complete resolution was observed in 23.1% (6/26) of patients in this study. These results are slightly higher than those of a previous study with aflibercept and ranibizumab (19.3%) . It is drovement .RPE tear is an important issue during anti-VEGF treatment owing to its association with poor visual prognosis . RPE teaIntraocular inflammation and retinal vasculitis with or without occlusion are the major adverse events in brolucizumab treatment . HAWK anTo our knowledge, this study is the first to investigate brolucizumab treatment of serous PEDs in PCV; however, it had several limitations. First, as it was an observational study, not all patients received the same treatment or had the same follow-up schedule. The PED responses may differ depending on the number and interval of brolucizumab injections. Second, we could not measure choroidal thickness on SD-OCT, which may be related to the responsiveness of serous PED in PCV due to the shadow effect of large serous PED. Third, owing to the small sample size, the statistical power was insufficient to reveal the baseline characteristics of the poor response group to brolucizumab treatment. Fourth, the follow-up period was short (4.27 ± 2.42 months).In conclusion, serous PEDs secondary to PCV showed significant anatomical improvements after brolucizumab injections. Functional improvement was not clear, but was observed in cases with complete resolution of PED. Response at 1 month after brolucizumab treatment is important to predict future prognosis, and relapse can be treated with additional brolucizumab treatment. RPE tears, IOI, and retinal vasculitis/obstructions were not observed. Further studies are necessary to better understand the mechanisms and responses of serous PED secondary to PCV to brolucizumab treatment.