Statistically significant differences in the functional and symptom scale scores were also observed within each group at different stages of cancer treatment. As shown by our study, the quality of life of patients treated for colorectal cancer is determined not only by the operating technique but also by sociodemographic and clinical factors. The use of minimally invasive surgical techniques enables patients to return to their social roles more quickly and improves their self-assessment of body image.This study constitutes a prospective, three-stage evaluation of quality of life among patients receiving surgical treatment for colorectal cancer depending on the type of surgery performed . The study included 82 patients treated at the Surgical Oncology Outpatient Department of the Oncology Center in Bydgoszcz from June 2019 to August 2021. The study tools consisted of diagnostic surveys and analyses of medical records. The standardized study tools were the surveys EORTC QLQ-C30 and QLQ-CR29. In addition, a proprietary questionnaire was developed to collect demographic data. Quality of life was measured at three time-points: the day before the surgery and 6 and 12 months post-surgery. Statistically significant differences ( A diagnosis of cancer is associated with stress, increased emotional tension, and uncertainty about distant outcomes. All these factors are frequently related to a reduction in the quality of life related to biopsychosocial functioning. Patients face new adaptational challenges, which frequently involve a change in the perception of their own body, a deterioration in physical fitness, and impairments in functioning in social roles . One of Colorectal cancer is the second most common cause of death from cancer in both genders in Poland and worldwide ,3. It isThe symptoms most commonly reported by patients include abdominal pain, changes in bowel movement patterns, changes in stool consistency, rectal bleeding, unjustified weight loss, depressed mood, and overall fatigue ,10. NotaThe goal of the cohort study was to prospectively evaluate the quality of life in patients treated for rectal cancer depending on the type of surgery performed.This prospective, three-stage, cohort observational study with a pretest–posttest design included 82 consecutive patients admitted to the Surgical Oncology Outpatient Department of the Oncology Center in Bydgoszcz for surgical treatment of colorectal cancer. The patients were divided into four study groups according to the type of surgery they underwent: 21 patients were qualified for abdominoperineal resection (APR), 13 were qualified for Hartmann’s procedure (HART), 27 for anterior resection (AR), and 21 for laparoscopic anterior resection (LAR). The type of surgery depended on the location of the lesion. In most distal lesions, APR was performed, while in cases of possible sphincter preservation with no option of sigmoid-rectal anastomosis, Hartmann’s procedure was introduced. For most proximal lesions, either laparoscopic or classic anterior resection was carried out by random selection. Every procedure was attended by a high-volume surgeon . The team performing the procedures included 10 surgeons. Anal sphincter function was not assessed before the procedure.Patients with a higher locoregional tumor stage and a higher risk of recurrence received neoadjuvant therapy consisting of radiation therapy with or without chemotherapy. All surgical procedures were performed at least 12 weeks after the initiation of radiotherapy and at least 4 weeks after the completion of chemotherapy, and they concerned only patients with residual tumor. In cases of complete response, resection was not performed. Adjuvant treatment was provided on the basis of pathomorphological diagnosis and consisted of chemotherapy or radiation therapy. Adjuvant treatment was provided to patients with a higher locoregional stage for up to 6 months after the treatment.The assessments were performed at 3 time-points: the first survey was administered on the day prior to the surgical procedure, while the second and third measurements were performed 6 and 12 months after the procedure, respectively. The study was approved by the Bioethics Committee at the Nicolaus Copernicus University in Toruń (No. 283/2019). Participation in the study was voluntary. Each participant was familiarized with the study design and gave their written consent to participate in the research project. They received in-depth information about the objective of the study, the study conditions, and their right to withdraw at any time without stating the cause and without any consequences.To ensure the uniformity of the sample and to exclude uncontrolled variables that could impact the study outcomes, inclusion and exclusion criteria were specified for the study.Inclusion criteria:−voluntary written consent to participate in the study−good overall health status when recruited (Eastern Cooperative Oncology Group (ECOG) score of 0–1)−hospitalization at the Clinical Department of Oncological Surgery of the Franciszek Łukaszczyk Oncology Centre in Bydgoszcz at the time of recruitment−elective surgery−no concomitant distant metastases−rectal cancer qualified to radical resection: abdominoperineal resection, anterior rectal resection (open or laparoscopic), or Hartmann’s procedure−clinical stage I–III (pTNM/ypTNM)−age over 18 years−good overall condition (ASA I–III)Exclusion criteria:−intraoperative conversion of surgical procedure−uncontrolled psychiatric disorders−other severe conditions that increase the risk of perioperative complications (ASA IV)−continuity of the digestive tract being restored in the course of follow-up−stoma formed during the first stage of the study procedure−distant metastases−stoma before surgery−other surgical procedures in the post-surgical follow-up period−survival of less than 12 monthsThe study was conducted using the diagnostic survey method. This method refers to the statistical collection of facts and information about structural and functional phenomena and their dynamics. The collected and grouped information on a given phenomenon allows us to determine its range, scope, level, and intensity. This in turn allows for an assessment of its causes and sequelae. Questionnaires are usually used in this method. The research tools included standardized questionnaires developed by the European Organization for the Research and Treatment of Cancer—the Quality of Life Questionnaire for Cancer Patients Version 3.0 (QLQ-C30) and the QLQ-CR29—the latter being a module dedicated to evaluating the quality of life of patients diagnosed with colorectal cancer. In addition, in order to evaluate the sociodemographic data of the study group, a proprietary questionnaire was constructed containing questions on age, gender, educational background, area of residence, employment status, number of children, marital status, and socioeconomic status.The EORTC QLQ-C30 is a validated tool for the self-assessment of quality of life in patients diagnosed with cancer, regardless of its location or stage of development. The questionnaire consists of five functional scales , three symptomatic scales , and the core scale for overall self-assessment of quality of life and health. The scale also contains six questions relating to symptoms such as loss of appetite, diarrhea, constipation, financial difficulties resulting from illness, dyspnea, and sleeplessness.The QLQ-CR29 is dedicated to assessing symptoms in patients diagnosed with colorectal cancer. The module contains 29 questions about the health problems experienced by patients treated for colorectal cancer. Better scores in the functional scales of the QLQ-C30 and QLQ-CR29 mean better performance in a particular aspect; with regard to the symptom scales, the higher the score, the higher the severity of the problem and the lower the quality of life .The patients’ medical records were analyzed to obtain relevant clinical data. The type of surgery, BMI, type of neoadjuvant treatment, type of adjuvant treatment, duration of hospital stay (between the day of surgery and the day of discharge), and TNM grade of the disease were collected for statistical analysis purposes.At the first stage of the study (June 2019–August 2020), the qualification criteria were evaluated for a total of 107 anterior resections, 88 laparoscopic anterior resections, 33 Hartmann’s procedures, and 56 abdominoperineal resections performed within that period at the Clinical Department of Oncological Surgery of the Oncology Centre in Bydgoszcz, Poland.Due to the restrictions connected with COVID-19 in Poland, the first phase of study recruitment lasted from June 2019 to March 2020 and was followed by a two-month break until recruitment could continue in July and August 2020. A total of 127 patients meeting the inclusion criteria were included in the study. There were 45 patients excluded from the study due to gastrointestinal tract continuity being restored during the course of the follow-up, patients being lost to follow-up, or patients providing incomplete answers to survey questions. The final analysis was therefore carried out among the 82 patients who had met the inclusion criteria and completed all stages of the study. The details are presented in Statistical analysis was carried out using the software program IBM SPSS Statistics ver. 27.0 . Inter-group comparisons of demographic variables and medical data were carried out using Fisher’s exact test for nominal variables and a univariate ANOVA for quantitative variables. Inter-group comparisons of the quality of life at each of the three time-points were carried out using multivariate mixed-model ANOVA with the type of procedure and triple measurements corresponding to the inter- and intra-group variances, respectively. The homogeneity of variance in the groups was verified using Levene’s test. The sphericity of the covariance matrix was estimated using Mauchly’s test. If the sphericity assumption was violated, the Greenhouse–Geisser correction was applied. For multiple comparisons, the Bonferroni test was used with a correction for the significance level.p < 0.05 was used as the significance level and p < 0.01 was used as the level for highly significant differences.Demographic and medical data that significantly correlated with the overall health status were identified by means of multiple linear regression analysis using the enter method. The collinearity of predictors was controlled using the variance inflation factor (VIF). Heteroscedasticity was estimated using the Breusch–Pagan test. Autocorrelation in the residuals was estimated by the Durbin–Watson test and by the visual plot-based method. The normality of the distribution of the residuals was estimated from a histogram. Model predictors were selected on the basis of correlation analysis, with only those variables that were significantly related to the quality of life being included in the model. A probability value of p = 0.257), age (p = 0.511), educational background (p = 0.417), area of residence (p = 0.930), employment status (p = 0.577), number of children (p = 0.737), marital status (p = 0.088), and socioeconomic status (p = 0.872). The analysis of anthropometric data—body weight (p = 0.966), height (p = 0.879), and BMI (p = 0.690)—also revealed no statistically significant differences between groups.The study groups, as distinguished by the type of surgery , were characterized using demographic variables and clinical data. The groups did not differ in terms of demographic data: gender (p = 0.491), duration of hospital stay (p = 0.204), and the TNM  grading of the disease (p = 0.204). No statistically significant differences were observed between the groups for these variables. As is shown by the analysis, the only significant difference between the groups was related to the type of neoadjuvant treatment (p = 0.021); however, the post hoc analysis failed to confirm such differences, which proved to be negligible (p > 0.05) in pairwise comparisons. It can therefore be assumed that the groups were similar in both demographic and medical terms. Male patients, urban residents, individuals in relationships, and those with two children prevailed in each of the groups. The average age of patients was about 62–67 years and the average BMI was about 25–27. The socioeconomic status of the respondents was reported as average or good in most cases. The mean length of hospital stay ranged between 7 and 13 days. The details are presented in The clinical characteristics of the study groups included the variables of adjuvant treatment (p > 0.05). At the third time-point, a statistically significant difference was observed in the role functioning scores (p = 0.030). A detailed post hoc analysis revealed that one year after the surgery, the quality of life related to role functioning was higher in patients who had undergone laparoscopic anterior resection as compared to those who had undergone open anterior resection of the rectum (p = 0.043). The differences between the other groups were not statistically significant (p > 0.05). For the remaining functional scales, no statistically significant differences were observed between the groups (p > 0.05).Statistical analyses were carried out to compare the four patient groups, which were distinguished by the type of surgery, using the EORTC QLQ-C30 functional and symptom scale scores at three time-points. The functional scales taken into account in the analysis included overall quality of life (QL), physical functioning (PF), role functioning (RF), emotional functioning (EF), cognitive functioning (CF) and social functioning (SF). The higher the score, the higher the subject’s quality of life. At the first and second time-points, no significant differences were observed in any of the functional scale scores between the study groups (p > 0.05).The dimensions of the symptom scales that were taken into account were fatigue (FA), nausea and vomiting (NV), pain (PA), dyspnea (DA), sleeplessness (SL), loss of appetite (AP), constipation (CO), diarrhea (DI), and financial difficulties (FI). The higher the score, the greater the severity. The statistical analysis revealed no statistically significant differences between the groups (p = 0.003), diarrhea (p = 0.024), and financial difficulties (p = 0.013). At time-point III, the emotional functioning level was much higher than at time-point I. The most severe symptoms on the diarrhea scale were observed prior to the surgery and they were completely resolved by time-points II and III. Financial difficulties were reported to be most aggravated 6 months after the procedure.The next step consisted ofexamining the changes in quality of life within each group, as assessed using the EORTC QLQ-C30 functional and symptom scales at different time-points. In the group of patients classified for abdominoperineal resection, statistically significant differences were found in the scores corresponding to emotional functioning (p = 0.004) and financial difficulties (p = 0.030). At time-point I, the quality of life in the social functioning domain was significantly higher than at time-points II (p = 0.014) and III (p = 0.006). No differences were observed between time-points II and III. Financial difficulties were also observed to be aggravated over time in this study group.Among the patients classified for anterior resection of the rectum, statistically significant differences were found in the scores corresponding to social functioning (p = 0.006), which means that a significant improvement had occurred within this domain.In the group of patients who qualified for LAR, significant differences were observed between the measurements within the emotional functioning domain. The reported level of social functioning at time-point II was significantly higher than at time-point I (p = 0.004). Significantly more severe complaints were observed at time-point II as compared to time-points I (baseline) and III (one year after the procedure). Detailed results are shown in Among the patients who qualified for Hartmann’s procedure, significant differences were observed with regard to the sleeplessness scale (The QLQ-CR29 questionnaire included questions related to self-assessed body image (BI), anxiety regarding prospects in life (ANX), weight problems (WEI), sexual function in women (SEXW), and sexual function in men (SEXM). In addition, disease symptoms were assessed: urination frequency (UF), blood and mucus in stool (BMS), stool frequency (SF), urinary incontinence (UI), dysuria (DA), abdominal pain (AP), buttocks/anal area/rectum pain (BP), bloatedness (BF), dry mouth (DM), hair loss (HL), taste anomalies (TA), flatulence (FL), fecal incontinence (FI), skin sensitivity (SS), and embarrassment (EMB). The higher the score, the more severe the symptoms and the lower the functioning.p > 0.05). At time-point II, statistically significant differences between the groups were reported with regard to body image (p < 0.001), sexual functioning (p = 0.033), and embarrassment (p = 0.022). The levels of embarrassment and difficulties accepting one’s own body image were significantly lower in patients who underwent laparoscopic anterior resection as compared to those who underwent abdominoperineal resection. The patients who underwent Hartmann’s procedure and abdominoperineal resection declared higher satisfaction with sexual functioning than those who underwent open or laparoscopic anterior resection. At time-point III, statistically significant differences between the groups were reported with regard to the scales of body image (p < 0.001), buttocks/anal area/rectum pain (p = 0.031), and embarrassment (p = 0.010). In the abdominoperineal resection patients, the difficulties accepting their body image were higher than in those who underwent laparoscopic anterior resection. Significant differences between the groups were also observed at time-point III on the scales of buttocks/anal area/rectum pain and embarrassment; however, the inter-group differences proved to be statistically insignificant after the significance level was corrected for multiple comparisons. The results of the analysis are summarized in At the first time-point, no significant differences were observed in any of the functional or symptom scale scores between the study groups (p = 0.001), urination frequency (p = 0.020), blood and mucus in feces (p = 0.025), abdominal pain (p = 0.006), buttocks/anal area/rectum pain (p = 0.049), bloatedness (p = 0.016), and embarrassment (p < 0.001). A highly significant deterioration in body image was observed at the second and third time-points as compared to the baseline. The severity of abdominal pain at time-point II was higher than that at time-points I and III. A simple effects test revealed that buttocks/anal area/rectum pain was more severe 6 months after the procedure than 12 months afterward. The incidence of bloatednesswas significantly lower at time-point III as compared to time-point II. The level of embarrassment at time-point I was significantly lower than at the other two time-points. The severity of urination frequency and blood and mucus in the stool at time-point I was significantly higher than at the two successive measurements, while the incidence of these symptoms at time-points II and III was at a similar level.The next step consisted of analyzing the changes in quality of life within individual groups at successive time-points. In the patients who underwent abdominoperineal resection, statistically significant changes in quality of life were observed in the domains of body image (p = 0.005), urination frequency (p < 0.001), blood and mucus in the stool (p < 0.001), hair loss (p = 0.028), and taste anomalies (p = 0.042). Significant deterioration was observed 6 and 12 months after the procedure in the domains of body image, hair loss, and taste anomalies as compared to the baseline measurements. The frequency of urination and the presence of blood and mucus in the stool were significantly higher at time-point I than the two successive measurements, though these symptoms were similar at time-points II and III.In patients having undergone AR, statistically significant changes in quality of life were observed in the domains of body image (p = 0.002), frequency of urination (p = 0.001), blood and mucus in the stool (p < 0.001), dry mouth (p = 0.008), and skin sensitivity (p = 0.038). With regard to anxiety, the highest scores were recorded 6 months after the procedure, with the results reported after 12 months being close to the baseline. The frequency of urination, the incidence of dry mouth, and the presence of blood and mucus in the stool were significantly higher at time-point I as compared to the two successive time-points, while these symptoms were similar at time-points II and III. With regard to skin sensitivity, the differences between the measurements were statistically significant; however, the significance disappeared after the results were adjusted for multiple comparisons.LAR was associated with changes in quality of life as regards anxiety regarding prospects in life (p = 0.003), buttocks/anal area/rectum pain (p = 0.013), and embarrassment (p = 0.018). The lower scores in body image and the higher scores in embarrassment observed at time-points II and III were statistically significant. Buttocks/anal area/rectum pain was significantly lower 12 months after the procedure as compared to time-points I and II. The details are summarized in In patients qualified for Hartmann’s procedure, statistically significant changes in the quality of life at successive time-points were observed in the domains of body image  and diarrhea . Prior to surgery, the patients who qualified for treatment with preservation of gastrointestinal continuity were more likely to report constipation than patients who qualified for treatment with intestinal stoma formation. Similarly, one year after operation, the problem was reported more frequently by patients without a stoma. At time-points II and III, higher scores suggestive of higher symptom severity were reported for the diarrhea domain in the patients without an intestinal stoma.The following section compares two groups of patients, those with and those without a stoma, using the functional and symptom scales of the QLQ-C30 questionnaire. The analysis revealed significant differences between these groups in the domains of constipation (time-point I: p = 0.031), emotional functioning (p < 0.001), social functioning (p = 0.041), sleeplessness (p = 0.013), diarrhea (p = 0.003), and financial difficulties (p = 0.005). In the group of patients with preservation of gastrointestinal continuity, significant differences in the scores reported at successive study time-points were reported for emotional functioning (p = 0.009), social functioning (p = 0.006), and financial difficulties (p = 0.014).Changes in quality of life, as reported at successive time-points, were observed between the stoma and no stoma groups. Statistically significant differences were found among the patients with intestinal stomas in role functioning , sexual functioning (time-point II: p = 0.013), blood and mucus in the stool (time-point I: p = 0.029), urinary incontinence (time-point I: p = 0.012), buttocks/anal area/rectum pain (time-point III: p = 0.003), bloatedness (time-point III: p = 0.009), hair loss , and embarrassment . Statistically significant differences were also observed at subsequent time-points. Among the patients with a stoma, these pertained to the domains of body image (p < 0.001), urination frequency (p = 0.002), abdominal pain (p = 0.001), buttocks/anal area/rectum pain (p = 0.001), bloatedness (p = 0.012), skin sensitivity (p = 0.049), and embarrassment (p < 0.001). For patients without a stoma, there were statistically significant differences in the domains of body image (p = 0.049), urination frequency (p < 0.001), blood and mucus in the stool (p < 0.001), stool frequency (p = 0.023), urinary incontinence (p = 0.023), and dry mouth (p = 0.007).The same analysis was performed with regard to the scales on the QLQ-CR29 questionnaire. It revealed significant intergroup differences within the domains of body image , which depend on the distance between the anastomosis and the anus, among other factors; these are referred to as anterior resection syndrome (LARS). This syndrome is defined as bowel dysfunction leading to decreased quality of life . DiffereNumerous studies have confirmed the impact that patients’ perception of symptoms have on the distant outcomes of surgical treatment for colorectal cancer, including the quality of life component ,2,16. OuAnother objective of our research was to assess the changes in quality of life within each group in the months following the procedure. Better emotional functioning over baseline levels was observed in all study groups, the improvement being most evident in the patients who underwent laparoscopic anterior resection or abdominoperineal resection of the rectum. Other researchers have observed that after 12 months of surgery for colorectal cancer, emotional functioning was better than before surgery and even better than in the healthy population , while mIn addition, our study demonstrated that the degree of sleeplessness assessed 6 months after surgery was higher among patients who underwent HART as compared to the baseline and the 12-month measurements. Similar complaints were described by other authors inpatients undergoing conventional open surgeries . In our In our study, the levels of embarrassment and difficulty accepting the changes to one’s body 6 and 12 months after the procedure were significantly lower in the laparoscopic anterior resection patients than in the abdominoperineal resection patients, which may be due to the extent of the latter procedure and its aftermath, including bodily mutilation. Moreover, body image was observed to deteriorate at successive time-points in all study groups, except for the patients who underwent laparoscopic anterior resection. In addition, in relation to the patients with stomas and those in whom gastrointestinal continuity had been preserved, difficulties accepting the new physical appearance after surgery were observed in both groups, being significantly worse among the former. Other authors also showed that the presence of a stoma negatively influences many QLQ domains ,23,26,27p = 0.0189) are significantly higher in patients who undergo anterior resection of the rectum [At the third time-point, statistically significant differences between groups were also found within the domains of buttocks/anal area/rectum pain; patients who underwent open or laparoscopic anterior resection reported more severe pain in these areas. Bloatedness, frequent urination, and the presence of blood and mucus within the feces were reduced after surgery regardless of the group. In the patients who underwent abdominoperineal resection, buttocks/anal area/rectum pain was found to be most severe 6 months after the procedure. Hartmann’s procedure was associated with a significant reduction in buttocks/anal area/rectum pain 12 months after the procedure. The results of studies by other authors show that the levels of pain (e rectum ,29. In oe rectum . Other re rectum ,32. In oThe pre-treatment results obtained in our study suggest that the quality of life was higher in individuals with higher socioeconomic status and in those running their own businesses instead of working on an employment contract. Induction radiotherapy was associated with a lower self-assessed quality of life. Six months after surgery, a higher quality of life was reported by male patients, better-off patients, and singles. At the third time-point, a higher quality of life was measured in those patients who had not received induction radiotherapy; again, quality of life was higher in those with higher socioeconomic status. The relationship between demographic and clinical data quality of life was also confirmed in other studies ,36,37,38In summary, these studies show that the quality of life of patients treated for colorectal cancer varies depending on the operating technique used, as well as sociodemographic and clinical factors. Despite its high scientific value, this study is burdened by several limitations. Firstly, the study groups were not randomized, and the patients’ eligibility was based on inclusion criteria alone. Secondly, the first measurement of quality of life was carried out the day before the procedure, which might have distorted the results in the emotional domains. The study groups were not identical in terms of perioperative treatment, and the patients in the LAR group were the least likely to have undergone preoperative treatment. No analysis of the potential correlations between quality of life and the distance between the tumor and the anal line was carried out within the groups of patients subjected to different operating techniques. It should also be noted that in most patients, the treatment started with induction radiotherapy, which, when used in the treatment regimen applied in the study patients, led to tumor downstaging, which could not have had no effect on their symptoms and QoL. Additionally, no analysis was carried out with regard to the adverse effects of neoadjuvant and adjuvant radiotherapy or chemotherapy. Moreover, it should be pointed out that no sphincter function was assessed before preoperative treatment or surgery. However, we believe that the symptoms of abnormal sphincter function were strictly dependent on the tumor stage and location, which determined the preoperative treatment and the type of surgery and thus naturally standardized the data. Moreover, no problems with stoma after APR or HART were observed. However, it should be pointed out that in both cases this is the same type of stoma, i.e., permanent end-sigmoid colostomy, which is connected with similar complications and sequelae.It should also be underscored that it is impossible to directly compare all groups. However, the quality of life is in a direct correlation with factors determining the type of surgical treatment, e.g., tumor location. Only the LAR and AR groups may be compared to some extent. We did not refer to LARS directly in the analysis . The synOn the other hand, we believe that because this was a single-center study from a center with a high patient volume, the risks associated with the lack of standardized surgical procedures was reduced, which has a fundamental impact on the potential complications and outcomes of resection procedures.This research is based on prospective studies, which reduces the risk of incorrect patient selection. This is a great advantage. However, the single-center character of the study determines another limitation, which is a small sample size.Patients who underwent abdominoperineal resection or Hartmann’s procedure reported worse body image and greater embarrassment due to their condition than patients who underwent open or laparoscopic anterior resection of the rectum. However, sexual activity was improved; buttocks/anal area/rectum pain, bloatedness, and constipation were less severe; and hair loss was less common among these patients.With regard to sociodemographic factors, the higher the economic status of patients, the higher their self-assessed quality of life. In addition, induction radiotherapy reduced the self-assessed quality of life. Significant deterioration in the economic status of subjects was observed, irrespective of the study group; this was least noticeable, however, among the patients who underwent laparoscopic anterior resection of the rectum.As compared to open anterior resection of the rectum, laparoscopic anterior resection contributed to better role functioning one year after the procedure.Anterior resection of the rectum was associated with a highly significant deterioration in the social functioning domain, which might have been due to anterior resection syndrome.


ASEAN (Association of Southeast Asian Nations) is composed of ten Southeast Asian countries bound by socio-cultural ties that promote regional peace and stability. South Asia, located in the southern subregion of Asia, includes nine countries sharing similarities in geographical and ethno-cultural factors. Chikungunya is one of the most significant problems in Southeast and South Asian countries. Much of the current chikungunya epidemic in Southeast Asia is caused by the emergence of a virus strain that originated in Africa and spread to Southeast Asia. Meanwhile, in South Asia, three confirmed lineages are in circulation. Given the positive correlation between research activity and the improvement of the clinical framework of biomedical research, this article aimed to examine the growth of chikungunya virus-related research in ASEAN and South Asian countries.The Scopus database was used for this bibliometric analysis. The retrieved publications were subjected to a number of analyses, including those for the most prolific countries, journals, authors, institutions, and articles. Co-occurrence mapping of terms and keywords was used to determine the current state, emerging topics, and future prospects of chikungunya virus-related research. Bibliometrix and VOSviewer were used to analyze the data and visualize the collaboration network mapping.The Scopus search engine identified 1280 chikungunya-related documents published by ASEAN and South Asian countries between 1967 and 2022. According to our findings, India was the most productive country in South Asia, and Thailand was the most productive country in Southeast Asia. In the early stages of the study, researchers investigated the vectors and outbreaks of the chikungunya virus. In recent years, the development of antivirus agents has emerged as a prominent topic.Our study is the first to present the growth of chikungunya virus-related research in ASEAN and South Asian countries from 1967 to 2022. In this study, the evaluation of the comprehensive profile of research on chikungunya can serve as a guide for future studies. In addition, a bibliometric analysis may serve as a resource for healthcare policymakers. Chikungunya virus, which was first isolated in Tanzania in 1953 , has beeAedes species and non-human primate species, such as monkeys, baboons, and mandrills [Culex and Anopheles have also been recognized as vectors of the chikungunya virus [Aedes albopictus and Aedes aegypti, which are reported as the primary vectors of chikungunya virus in Asia, Oceania, Europe, the Americas, and Africa [A. aegypti also transmits other types of viruses, including dengue virus and zika virus, as supported by several studies reporting the occurrence of dengue/chikungunya/zika virus or dengue/chikungunya virus simultaneous infections [The transmission routes of the chikungunya virus mostly occur via urban and sylvatic cycles . The sylandrills –30. In rya virus . Transmid Africa –36. Notafections –39. At pfections , 41. Recfections –48.The primary goals of ASEAN, also known as the Association of Southeast Asian Nations, are to foster regional stability and economic progress among its members . ASEAN cAmong South Asian countries, India is estimated to contain the highest number of chikungunya virus infection cases , 61–63. Bibliometric methodology has been established as a primary tool to evaluate research performance in various fields, including health , 73, sciDocuments associated with the chikungunya virus from ASEAN and South Asian countries indexed in Scopus from 1967 to 2022, excluding erratum and retracted articles, were extracted for our bibliometric study. To avoid including duplicate or invalid documents in the analysis, erratum and retracted articles were excluded. In this study, the Scopus database served as our sole data source because it covered a large range of journals and a high number of articles relative to other libraries such as Web of Science or PubMed , 94. Scon = 4107). Our search results, focusing on ASEAN and South Asian countries, included 1011 (78.98%) articles, 103 (8.04%) letters, 92 (7.18%) reviews, 20 (1.56%) notes, 17 (1.32%) conference papers, and 39 (3.04%) other types of documents, including book chapters, editorials, notes, and short surveys. Among the published documents, English is the most common language, accounting for 1279 (99.92%) of the total documents.From 1967 to 2022, the Scopus algorithm identified 1280 documents published by ASEAN and South Asian countries in the chikungunya-related field, accounting for 31.11% of the global productivity (n = 12) builds collaborative studies with more countries compared to the Maldives (n = 2).The chikungunya virus publishing trend in ASEAN and South Asian countries exhibited a gradual increase from 1967 to 2022 , followed by PLoS ONE , and the Indian Journal of Medical Research . Also, the characteristics of papers published by ASEAN and South Asian countries with the highest number of citations in the last five decades were summarized (Table The productivity among ASEAN and South Asian countries in research documents related to the chikungunya virus was also ranked, with India having the highest percentage Table . The topAedes”, “disease outbreaks,” and “alphavirus infection” in 2013; “epidemic,” “reverse transcriptase polymerase,” and “antibodies” in 2014; “isolation and purification,” “arthralgia,” and “dengue” in 2015. In 2016, research on “virology,” “animal cells,” “mice,” and “immunology” gained a significant attention in the field of chikungunya studies. Importantly, from 2017 onwards, the published articles mainly reported on “virus replication,” “metabolism,” “physiology,” “antivirus agent,” and “genetics” chikungunya virus, indicating that these terms are emerging and gaining significant attention in the last few years. The institutions from ASEAN and South Asian countries with the highest productivity in the field of chikungunya from 1967 to 2022 were also listed, highlighting the prominent contributions of India, Singapore, and Thailand (Table A network visualization of terms used by authors from ASEAN and South Asian countries in the 55-year period of chikungunya virus-related research was constructed Fig. a. The exOur research provided new perspectives on the scientific contribution of ASEAN and South Asian countries to chikungunya virus-related research. In general, ASEAN and South Asian countries contribute 31.11% of the global production of chikungunya virus-related studies. In 2006, the number of articles published by ASEAN and South Asian countries increased dramatically, from 2 documents in 2005 to 19 documents in 2006. After 2006, a gradual increase in chikungunya-related documents produced by ASEAN countries was observed, indicating that chikungunya virus-related topics are gaining prominence as a human health concern. A closer examination of the documents published in 2006 reveals that India, with 15 documents, contributed the most articles. Articles published in 2006 mostly discussed the re-emergence of the chikungunya virus in India and Malaysia , 110. MeIn bibliometric analysis, directly evaluating the weight or effect of publications is difficult. However, a number of studies argued that important insights could be obtained by analyzing the relationship between article relevancy and journal significance , 122. InAfter 2017, the topics of antiviral activity and neutralizing antibodies are emerging as the new focus on chikungunya-related studies in ASEAN and South Asian countries. Effective antiviral strategies are required to combat the rising prevalence of chikungunya virus infection and reduce mortality. Because there are no effective vaccines, significant research has been conducted to discover potent antivirals against the chikungunya virus Table . In paraA. aegypti and A. albopictus [The majority of global efforts have been devoted to concentrating on treating symptoms and preventive measures, because there are no commercially available vaccines or medications to cure chikungunya infections . The mitbopictus , 162. Efbopictus , 164. AdThis study uses a bibliometric technique to assess the current state and trajectory of chikungunya virus-related research published by ASEAN and South Asian countries. However, a few limitations, which also appear in other bibliometric analyses, were identified. First, our study registered the key term “chikungunya” only for title searches. Our analysis may have overlooked any publications that utilized the keyword “chikungunya” in the abstract or within the publication. Second, this study focused on publications indexed in the Scopus library. Although Scopus is the most widely used and trusted database, a few outlier papers may have been left out. Despite these limitations, our bibliometric study is the first to provide a concise overview of the chikungunya virus-related research profile by ASEAN and South Asian countries. Our research also demonstrates how bibliometric analysis may be used to estimate research productivity in the field of chikungunya.Our study is the first to present the contribution of ASEAN and South Asian countries to chikungunya virus-related research. By integrating literature review and bibliometric analysis, the current study aimed to provide an outline of the progress, current trend, and emerging topics in the field of chikungunya in ASEAN and South Asian countries. Over the past two decades, the research productivity on chikungunya virus-related topics in ASEAN and South Asian countries has increased remarkably, with a total of 1280 articles published in prominent journals. Previously, researchers prioritized studies related to the vector, infection, and nucleotide sequence of the chikungunya virus. However, in recent years, the research topics have shifted to the development of antiviral drugs and the genetics of chikungunya virus. Out of ten ASEAN countries, Thailand contributes the highest number of articles related to chikungunya, followed by Singapore. Meanwhile, India ranks first among South Asian countries in terms of productivity. The findings of this study can serve as a reference for ongoing chikungunya virus-related research and policymakers working in the field of healthcare, particularly in ASEAN and South Asian countries.


Adult-onset Still Disease (AoSD) is a rare disorder without standardized diagnostic criteria. People are paying more and more attention to its research. At present, no published studies have assessed the AoSD field using bibliometric tools. This study aimed to analyze research hotspots and frontiers through bibliometrics to provide a scientific and accurate reference for new and existing researchers.Data were obtained from the Web of Science core database and analyzed by CiteSpace, VOSviewer, and Microsoft Excel.Involving 86 countries and regions, a total of 11,121 authors published 2,199 articles in 676 journals. These studies were published from 1976 to 2020. The United States published the most related articles (397). The United States, France, Italy, and Germany were the top four countries with a high H-index. Authors and institutions with high number of published articles and high citations are mainly located in France and Italy. High-frequency keywords include classification, criteria, diagnosis, and therapy method. Keyword clustering covers the connection between AoSD and rheumatoid arthritis, disease diagnosis, classification, and risk factors.The research on AoSD focuses on the diagnosis and differential diagnosis of the disease. Targeted therapy will become a research hotspot in the future, and relevant clinical research needs to appropriately expand the sample size and improve the credibility of the conclusions. The data reported in this study can serve as a useful resource for researchers studying AoSD. Adult-onset Still Disease (AoSD) is a systemic autoinflammatory disease. In 1971, Bywaters analyzed the clinical and laboratory characteristics of 14 adult patients. He found that these characteristics were very similar to systemic-onset juvenile idiopathic arthritis (SoJIA), a condition also known as Still disease. From these observations, he named the disease AoSD  genotype is closely related to the pathogenesis of several diseases. Furthermore, HLA-Bw35, HLA-B17, HLA-B18, HLA-B35, HLA-DR4, HLA-DRw6, etc., are thought to be closely related to the onset of several diseases –12. GiveBoth the innate and adaptive arms of the host immune response are involved in the pathogenesis of AoSD, of which macrophages, neutrophils, and serum cytokines play a key role. Inflammasome activation, like NLRP3 inflammasome , by pathogen-associated molecular patterns and damage-associated molecular patterns , 16 incrBibliometrics is a comprehensive knowledge system that integrates mathematics, statistics, and linguistics. It is widely used to explore development trends and research frontiers in various fields . HoweverThis study was included literatures on AoSD as the research topic. Article types were limited to “article” and “review.” Conference abstracts, letters, expert views, editorial materials, corrections, retractions, and proceedings paper were excluded.All publications included in this study were collected from the Science Citation Index Expanded (SCI-E) through the Web of Science Core Collection (WoSCC) database on October 24, 2021. The search formula was set to TS = (Adult-onset Still Disease), and the period of published studies assessed was from 1976 to 2020, the language restriction was English. Two researchers (BH Bao and BW Xu) cross-checked the included article, and when there were disparities, the third researcher (XY Meng) made a final decision. The process of study screening is shown in VOSviewer version 1.6.17, Citespace 5.8.R3 and Microsoft Excel 2020 are used for data analysis and visualization of AoSD article studies. VOSviewer and Citespace are bibliometric analysis softwares. These softwares were used for co-word analysis, co-citation analysis, and article coupling analysis. They can visualize the research results and has unique advantages in clustering technology and map display . MicrosoBy using search strategy, a total of 2,864 published studies and reviews were retrieved. After the removal of duplicate documents, 2,199 articles remained. Changes in the number of publications and citations can reflect the development status of a field and predict future research trends. The total citations and average citations were 63,073 and 28.68, respectively. The H-index was 106. Searching within the WoSCC database, the first available article on AoSD was published in American Family Physician in 1976. In the past 10 years, the number of publications and citations of AoSD article has steadily increased year over year. In 2020, the number of publications and citations of related articles reached peaked at 231 and 11,731. As shown in From 1976 to 2020, scholars from 86 countries and regions have published AoSD research. Among them, scientists from the United States published the most . The Top 10 countries with more than 200 publications included Italy , France , Japan , and Germany  . From thRegarding specific research institutions, we found that 2,588 research institutions have conducted AoSD research. The main institutions by number of publications include Assistance Publique Hopitaux Paris (105 publications), Institut National De La Sante Et De La Recherche Medicale (68 publications) and Sorbonne Universite (53 publications). These data indicate that these three institutions are specialized in the field of AoSD research. Further, it is evident that France occupies a dominant position in the field .Academic exchanges and cooperation between different countries/regions, institutions, and authors play an important role in expanding the depth and horizons of research. When parameters of academic cooperation and exchange in AoSD research were assessed, it is evident that collaboration, training, and information exchange occur at multiple levels .VOSviewer software was used to visualize the collaboration between countries, institutions, and authors . Each noThe node connection length reflects the closeness of cooperation between two different institutions. Our analysis revealed that a total of 216 research institutions have published at least five research documents. Circles/nodes in different colors represent a cooperative group. Twelve cooperative groups with the closest cooperation were identified. The University of Padua, the University of L'Aquila, and Harvard University have carried out the most academic cooperation with other research institutions. As shown in Co-author analysis revealed a total of 11,121 co-authors in the AoSD field. Giacomelli R (27 articles) has published the most articles, followed by Ruscitti P (26 articles) and Kim Ha (25 articles) . Our datThe Top three most-cited authors were Fautrel B , followed by Piette JC (901 citations), and Giacomelli R (753 citations). The majority of institutions where the Top 10 authors, by publications and citations, were affiliated were located in France and Italy . YamagucClinical Rheumatology (IF 2.98), the Journal of Rheumatology (IF 4.666), Rheumatology International (IF 2.631), and Medicine (IF 1.889). The Top four journals cited are the Journal of Rheumatology (IF 4.666), Medicine (IF1.889), the Annals of the Rheumatic Diseases (IF 19.103), and Clinical Rheumatology (IF 2.98); all of which have been cited more than 1,500 times , the Annals of the Rheumatic Diseases (IF 19.103), and Arthritis & Rheumatology (IF 10.995)  and journal quartile were obtained from Journal Citation Reports 2020. The Top four most productive journals are 00 times . The Top 10.995) . The maj 10.995) . These dThe Top thee co-cited references as follows: “Preliminary criteria for classification of adult stills disease” by Yamaguchi et al.  653 cit. The secCo-cited references clustering can reflect the frontier direction of research field or unresolved scientific topics to a certain extent, which contains the emerging trend of research. The main clusters of co-cited references on AoSD focus on the treatment , clinical manifestations and accompanying symptoms , differentiation from other rheumatic immune diseases , and autoimmune reactions (#7). As shown in The Top three articles with the most citations included Yamaguchi et al.  1,081 c1 c8 482 435 cit has beenKeywords can also reflect frontiers and hotspots in a particular field. The Top 10 keywords with the highest occurrence frequencies in the article assessed in this study were “classification” (184), “criteria” (177), “rheumatoid-arthritis” (161), “juvenile idiopathic arthritis” (144), “manifestations” (139), “diagnosis” (137), “children” (129), “macrophage activation syndrome” (98), “adults” (94), and “efficiency” (83).By clustering keywords with a frequency >5, a total of 446 eligible keywords were clustered into seven groups. Nodes with the same color represent the same cluster . The cluThis study uses a variety of bibliometric software and tools to analyze the published research article on AoSD based on the WoSCC database. Studies have shown that the earliest retrospective article was published in 1976 .By 2020, the annual number of publications and citations of AoSD-related research showed an overall upward trend, thus highlighting the rapid development of AoSD studies and sustained interest in its research. However, as an orphan disease, AoSD has a low incidence in the population with the prevalence rate estimated to be one case per million people in Europe and 10 cases per million people in Japan . This loThrough the comprehensive and systematic summary of the research topics, trends, and global research on the impact of AoSD, scholars can quickly and preliminarily understand the current state of AoSD research. The H-index reflects the academic achievements of countries, institutions, or individuals in a certain field. The higher the H-index, the greater the academic influence. From the perspective of regional distribution, the United States is the global leader in terms of both the number of published article and H-index in AoSD-related research. Specifically, AoSD research originating in the United States has significantly contributed to the field. However, in the current study, further analysis of research institutions and individuals revealed that France and Italy may have superior contributing roles to global AoSD research. This is especially valid when assessing the Top 10 authors by the number of publications and citations. Further, these data indicated that no American scholars were found in the Top 10, and French and Italian scholars occupy the majority.Keyword cluster analysis can highlight current research hotspots. In agreement with the research direction of highly cited articles and co-cited references, our data indicate that the research hotspots of AoSD are mainly related to the identification and diagnosis of the disease. These hotspots may be attributed to the fact that as an orphan disease, the pathogenesis of AoSD is not clear, and multiple factors including heredity, infection, and immune dysfunction may contribute to AoSD development. As an immune-related disease, AoSD is difficult to distinguish from juvenile rheumatoid arthritis and rheumatoid arthritis (RA) in the initial clinical diagnosis.3, polymorphonuclear count ≥80%, and glycosylated ferritin ≤20%. Of these criteria, maculopapular rash and leukocyte count ≥10,000/mm3 are considered to be secondary, and the remaining six signs are considered to be the primary criteria. Using these parameters, a positive AoSD diagnosis would be defined as a patient presenting with four primary criteria, or three primary criteria +2 secondary criteria. Studies have shown that these diagnostic criteria have a higher sensitivity relative to traditional diagnostic strategies , just concluded the update in June 2021, and no relevant literature has been published. In addition, systematic reviews are indicating that the use of IL-1β inhibitors in AoSD has led us to a new era of targeted therapy for AoSD (We found that research on targeted therapy for AoSD has been on the rise. As early as 2007, Efthimiou suggested that recent advances in basic immunology have improved our ability to hinder the pathogenic mechanisms associated with AoSD, and discussed the impact of targeted anti-inflammatory cytokine-based targeted therapies on AoSD , 38, 39.for AoSD . Whilst for AoSD . TherefoDue to the rarity of AoSD, many clinical studies are limited by small sample sizes and are thus underpowered. Furthermore, because of the varying clinical designs among different studies an accurate consensus is difficult to conclude. These are significant obstacles that need to be overcome to improve the credibility of published AoSD studies in the future.Analysis of AoSD article by Citespace and Vosviewer has some limitations. The first is the deadline for article retrieval by 2020, but as WoSCC continues to update, the number of articles retrieved in this study may be slightly different from the actual number of relevant articles. The Second, due to the possible time lag, the importance of some studies, especially some newly published article, may not be given sufficient attention at present. Finally, the use of single database WOSCC is also a limitation. However, its use can be further substantiated, as it provides more accurate document type labeling than other databases such as Scopus . And thiThis study analyzed AoSD research published from 1976 to 2020. Furthermore, we summarized the regional distribution, journal category, article citation, main cooperative groups, and keyword clustering related to AoSD research. As an understudied, orphan disease, the mechanisms and pathogenesis of AoSD still need to be elucidated. The development of targeted AoSD therapy is a relatively effective and safe. However, existing clinical research samples sizes are small and prone to Type I or Type II errors. It is necessary to further expand the clinical sample size and clarify the safety and effectiveness of biological agents. This study provides key insights into current AoSD research and can be used as a useful resource for researchers in the field to identify hotspots and trends.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.BX and BB conceived the study. BX, JW, and XM collected the data. BB re-examined the data. BB and XM analyzed the data. BX wrote the manuscript. JW, BB, and XM reviewed and revised the manuscript. All authors have read and agreed to the published version of the manuscript.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The purpose of our study was to investigate the effect of objective sleep characteristics on the incidence of depression.The participants of our study  were selected from the Sleep Heart Health Study (SHHS) datasets. Depression was defined as the first occurrence between SHHS visit 1 and visit 2. Objective sleep characteristics, including sleep efficiency (SE), wake after sleep onset (WASO), sleep fragmentation index (SFI) and arousal index (ArI), were monitored by polysomnography. Multivariable logistic regression was used to explore the relationship between sleep characteristics and depression.P = 0.016) and WASO  were associated with the incidence of depression. Moreover, the relationship between SE and depression was more pronounced in men  than in women  in subgroup analysis (Pinteraction < 0.05).A total of 248 patients with depression (7.3%) were observed between SHHS visits 1 and 2. After adjusting for covariates, SE (odds ratio [OR], 0.891; 95% confidence interval [CI] 0.811–0.978; SE and WASO may be markers for the incidence of depression. The association between SE and depression was intensified in men. Depression, characterized by feelings of sadness, slowed thinking, and loss of interest, is one of the main causes of disability and the overall disease burden around the world . The numPrevious observational studies have demonstrated a bidirectional relationship between sleep disorders and depression , 6. InsoPolysomnography (PSG) is usually employed to monitor sleep characteristics such as SE, WASO, sleep fragmentation index (SFI), and arousal index (ArI) in total sleep, REM sleep and non-REM (NREM) sleep. The aim of our study was to investigate the effect of objective sleep characteristics on the incident of depression based on PSG records.ClinicalTrials.gov Identifier: NCT00005275) was a dataset consisting of nine existing “parent” cohort studies including the Framingham Offspring Cohort, the Hagerstown and Minneapolis/St. Paul sites of the Atherosclerosis Risk in Communities study, the Hagerstown, Sacramento, and Pittsburgh sites of the Cardiovascular Health Study, the Strong Heart Study sites in South Dakota, Oklahoma, and Arizona; and studies of respiratory disease in Tucson and of hypertension in New York. There was a clear data quality assurance and control system for the SHHS. All participants provided written informed consent, and the study was approved by the ethical review board at each site (https://doi.org/10.25822/ghy8-ks59). Between 1995 and 1998, SHHS visit 1 collected information about in-home PSG records, demographics, sleep habit questionnaires, and medical histories. SHHS visit 2 was performed between 2001 and 2003. In this study, individuals were excluded if they had (1) missing data at follow-up (n = 777), (2) previous depression (n = 420), (3) missing depression status (n = 433), and (4) not followed at SHHS visit 2 (n = 799). Finally, 3,375 participants were included in the study.Data on the participants in the present study was obtained from the Sleep Heart Health Study (SHHS). The SHHS . The PSG was set up by a team that included a sleep technician and an assistant. PSG records were obtained in an unattended environment. The next morning, a technician returned to the participant's home at a Pre-arranged time to collect the sleep monitors. If the record is insufficient, a repeat PSG monitor request is initiated. The entire monitoring process tried to keep the participants consistent with their usual sleep. SFI refers to the number of awakenings plus sleep-stage shifts divided by total sleep time. SE is calculated as the total sleep time divided by the time in bed. WASO is defined as the period of wakefulness that start from first falling asleep to being fully awake and no attempt to go back to sleep. The ArI is calculated by dividing the number of arousals by the total sleep time . Apnea-hDepression status was based on the diagnosis and medication history of the “parent” cohort study. All depression medications were recorded during the interview. Medication information was later categorized by a physician review. Depression was defined as the first occurrence between SHHS visit 1 and 2 in this study.Information about age, sex, race, education, marital status, smoking status, alcohol use, benzodiazepine use, sleep duration, history of common disease , and history of major cardiovascular disease  were obtained at baseline.t-tests were employed to detect the difference between the depression and control groups. Multivariable logistic regression was used to examine the effect of each individual sleep parameter  on the incident of depression. The results were reported with odds ratios (ORs) and 95% confidence intervals (CIs). Each individual sleep parameter was adjusted for age, sex, race, education, marital status, smoking status, alcohol use, benzodiazepine use, sleep duration, history of common disease, and history of major cardiovascular disease in multivariable logistic regression analysis. Based on multivariable logistic regression analysis, subgroup analysis was performed to further explore the association between objective sleep characteristics and depression stratified by sex (men vs. women). All statistical analyses were conducted using SPSS . A two-sided P value of < 0.05 was considered significant.Baseline characteristics are presented as mean (SD) for continuous variables and number (percentage) for categorical variables. Chi-square tests and independent sample A total of 248 patients with depression were observed between SHHS visit 1 and 2. Depressive patients had more women and benzodiazepine use than the controls. Individuals with depression also had relatively low levels of education. In addition, patients with depression were prone to have decreased SE and increased WASO. The baseline characteristics of the patients with and without depression are shown in P = 0.016) and WASO  were significantly associated with the incidence of depression . The incidence of depression among the participants with SE ≥ 90%, SE 85.0–89.9% and SE < 85.0% were 3.7, 4.3, and 8.1% (P = 0.003) in men and 7.6, 7.9, and 9.4% (P = 0.478) in women, respectively (P = 0.007), but the association was not found in women . Furthermore, no significant interaction was found when subgroup analysis was stratified by sex in the relationship between other sleep parameters and depression.We further conducted a subgroup analysis stratified by sex to investigate the effect of sleep characteristics on depression risk . A signiectively . After mIn the present study, we observed an association between sleep characteristics and the incident of depression. Our findings were based on SHHS, which is a large community-based population of middle-aged and elderly individuals. We provided evidence that decreased SE and long WASO were associated with an increased risk of depression. The association between SE and depression was more pronounced in men than in women in the subgroup analysis.Several common factor, including restless leg syndrome, alcohol consumption, caffeine intake, poor sleep environment and chronic diseases such as bronchitis and angina pectoris, could cause sleep problem , 16. PSGPinteraction < 0.05). SE was found to be closely related to depression in men but not in women. Moreover, the relationship between WASO and depression was more pronounced in men than in women. Our findings indicate that more attention should be paid to individuals with poor SE in order to reduce the risk of depression, especially in men.SE and WASO could reflect the general estimation of the overall quality of sleep . Our resThe mechanisms underlying the effects of SE and WASO on depression are not fully understood. SE and WASO were commonly used to measure objective sleep quality, while low SE is often accompanied by long WASO . PreviouThis study had several strengths and limitations. We investigated the role of sleep characteristics in the incident of depression based on a relatively large community-based population. In addition, all sleep parameters were objectively monitored using in-home PSG. Depression was defined as the first occurrence between SHHS 1 and 2 visits. However, there was no information about the specific follow-up time of depression diagnosis; therefore, we used logistic regression analysis to explore the association between objective sleep characteristics and the incidence of depression. Moreover, the participants in the SHHS datasets were middle-aged and elder people; therefore, the findings may not be generalizable to younger individuals.We provided evidence that poor SE and long WASO may increase the risk of depression. The associations between poor SE and depression were more pronounced in men than in women. Improving sleep may help reduce the risk of depression.https://doi.org/10.25822/ghy8-ks59.The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: The studies involving human participants were reviewed and approved by Boston University Case Western Reserve University Johns Hopkins University Missouri Breaks Research, Inc. New York University Medical Center University of Arizona University of California at Davis University of Minnesota – Clinical and Translational Science Institute University of Washington. The patients/participants provided their written informed consent to participate in this study.BY and XM raised the idea for the study. BY, BZ, XJ, WX, LY, and JY contributed to the study design, writing, and review of the report. BY and XM acquired the data in SHHS and BY participated in further data analysis. XM handled supervision in our study. All authors approved the final version of the report.This study was supported by the Natural Science Basic Research Program of Shaanxi (No. 2021JQ-395).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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The mean gestational age in the groups of IVC and SVC was 31.43 weeks and 32.16 weeks, respectively. The mean birth weight in the groups of IVC and SVC was 1642.18 g and 1792.00 g, respectively. Placement of an S12-4 ultrasound sector transducer to obtain clear parasternal views of the aorta allows visualization of PCVC tips in the SVC and near the cavoatrial junction. PCVC repositioning rates were not significantly different between the two groups (p = 0.092). Sonography examinations in the SVC had a longer duration than those in the IVC (p < 0.001). Sonography provides an accurate method for determining PCVC tip location in the SVC. Malposition of percutaneous central venous catheters (PCVCs) in the superior vena cava (SVC) is common. We previously showed that real-time sonography was safer and faster than radiography in identifying PCVC tip location in the inferior vena cava (IVC). However, in preterm infants, determining PCVC tip location in the SVC is complicated by endotracheal or nasogastric tubes in situ and emphysematous lung conditions. We aimed to find an appropriate sonographic view by which to assess PCVC tip location in the SVC compared to the sonographic examination of PCVC in the IVC. Neonates ( Percutaneous central venous catheter (PCVC) insertion is a common procedure performed for critically ill patients, especially on very preterm neonates in the neonatal intensive care unit (NICU), to prepare for fluid infusion, prolonged medication administration, and parenteral nutrition. PCVCs are inserted into peripheral veins on the arms or legs, and finally end up within the superior vena cava (SVC) and near the cavoatrial junction, or the inferior vena cava (IVC) near the right atrium. Among central lines in neonates, PCVCs are associated with more indwelling complications than other central lines  . The malThis prospective cohort study was conducted in a level III, thirty-three-bed NICU from January 2021 to December 2021. Fifty neonates (SVC group) who had PCVCs in the SVC were enrolled to assess the location of the tip by ultrasonography. Because the assessment of tip location of PCVCs in IVC in the NICU had already been routinely performed by ultrasonography in our previous study, the medical records data of fifty neonates who had PCVCs in the IVC (IVC group) were retrospectively reviewed as the comparative data. Patients’ gestational age (GA), birth weight (BW), gender, age, and body weight at the moment of intervention were matched between the SVC and IVC groups. All tip positions of PCVCs were finally confirmed by radiography after ultrasonography. The repositioning rate, duration of intervention, duration of tip assessment by sonography, and the duration of tip assessment by radiography, the complication of PCVCs, such as catheter-related bloodstream infection (CRBSI), occlusion, and unexpected removal, were compared between SVC and IVC groups. The SVC group was further divided into invasive ventilation and non-invasive ventilation subgroups for analyzing the influence of ventilation on finding PCVC tips located in SVC. Invasive ventilation is defined as positive pressure delivered to a patient’s lung via an endotracheal tube, whereas non-invasive ventilation is via a nasal device. The repositioning rate means the rate of repositioned PCVCs after final radiography. The duration of the intervention is defined as the time from inserting the needle through the skin to advancing to the estimated length. The duration of tip assessment by sonography is defined as the time from putting the probe on the chest wall until visualization of the proper tip location, including normal saline fluid flushing, tip location adjustment, and a four-chamber view exam. The duration of tip assessment by radiography is defined as the time from ordering and taking the radiography until the confirmation by the neonatologist. CRBSI is defined according to the Nosocomial Infections Surveillance System from Taiwan Centers for Disease control in 2018. An eligible bloodstream infection (BSI) organism is identified and an eligible central line is present on the date of laboratory-confirmed BSI or the day before. An eligible central line means that the central catheter has been already in place for more than two calendar days. The unit of CRBSI is per 1000 central-venous-catheter days. An unexpected removal was defined as removal that resulted from an unresolvable complication.All PCVCs were inserted under sterile maneuvers and performed by the same nurse practitioner and neonatology fellow. The PCVCs used in the SVC group were 2.0 French single-lumen catheters, with internal stiffening stylet Bard Per-Q-Cath . The ideal distance for insertion was estimated by the equations which were reported in our previous study . The inst-test and Fisher’s exact test were used to analyzing continuous and categorical data, respectively. All tests were two-tailed and statistical significance was established as p < 0.05.To compare both groups, SVC and IVC, the data for gestational age, birth weight, gender, age, and body weight on the intervention date were examined. The duration of tip assessment by both ultrasonography and radiography, the procedure length of intervention, the repositioning rate, and the complication of PCVCs, such as CRBSI, occlusion, and unexpected removal were also analyzed for the comparison. Student’s p = 0.09). Furthermore, in the SVC group, patients with/without invasive ventilation also did not have significant differences in all variables which were presented in p < 0.001). Although the invasive ventilation group had a little longer duration than the non-invasive ventilation group, it was not significantly different. Besides, the complications of PCVCs, such as CRBSI, occlusion, and unexpected removal, were also insignificantly different between the two groups, as presented in Fifty PCVCs were placed in each SVC or IVC group during the study period. The mean gestational age in the groups of IVC and SVC was 31.43 ± 5.11 weeks (range: 26.28–36.18 weeks) and 32.16 ± 4.21 weeks (range: 29.43–35.11 weeks), respectively. The mean birth weight in the groups of IVC and SVC was 1642.18 ± 984.97 g (range: 820.00–2592.50 g) and 1792.00 ± 844.63 g (range: 1147.50–2387.50 g), respectively. The mean body weight at the moment of intervention in the groups of IVC and SVC was 2035.60 ± 1036.72 (range: 915.00–2430.00 g) and 1819.40 ± 1210.06 (range: 1243.75–2685.00 g). No significant differences were noted between the SVC and IVC groups in GA, BW, gender, age, and body weight at the moment of intervention, duration of intervention, and duration of radiography. The repositioning rate in the IVC group was 4% and in the SVC group was 16%, indicating no significant between-group difference (Results of the present study have demonstrated that the tip location of PCVCs inserted into the SVC can be detected accurately by ultrasonography. The rate of repositioning in the SVC was higher than that in the IVC group, but not significantly different. Thus, it becomes more critical to evaluate PCVC tips in the SVC by ultrasonography than those in the IVC. However, the mean time of the ultrasonography exam for PCVCs in the SVC was 12.5 min, which was significantly longer compared to locating PCVC tips in the IVC. However, ultrasonography was faster than radiography evaluation for PCVCs in either the SVC or IVC, which allows immediate administration of medications or nutritional supplementation with no delays. Although the repositioning rate of PCVC in SVC was higher than IVC group, it was not significantly different. The PCVC migration commonly happened within the first day . Others The mean time for waiting for an X-ray examination was 150–160 min in this study which was a long time for an ICU order. The portable radiography in our hospital could be ordered urgently or not, but checking the location of PCVC is not urgent. Thus, it cannot be ordered at a definite time and must wait. However, there was no difference in time taken X-rays in and out of hours in our hospital because the number of portable radiography devices during the working hour was similar to during off-hours, which did not prolong the waiting time. Certain difficulties must be overcome during ultrasound assessment of PCVCs in the SVC. First, PCVC tips were hard to visualize in a collapsed SVC, which may occur as a result of positive pressure ventilation. Because increasing positive pressure of mechanical ventilation will decrease intrathoracic great venous return and reduce right ventricle preload, further blood flow is prevented . HoweverThe present study has a few limitations, including that the two groups of different patients were enrolled at different times. Although all PCVCs were assessed by the same neonatology fellow, ultrasonography skills are expected to increase over time. The ultrasonography of PCVC in IVC had been performed for more than one year, which was longer than PCVC in SVC; besides, the IVC group data were reviewed retrospectively, and SVC group data were reviewed prospectively, which may cause certain biases. However, the repositioned PCVCs were not significantly increased in the SVC group in this study. Thus, the influence of the ultrasonography technique in this study was minimal. According to our experience, better ultrasonography skills may be needed in evaluating the SVC group than the IVC group, as so many obstacles must be overcome. Therefore, specialized training in the ultrasonography examination should be taken. Before the beginning of this study, the neonatologist fellow who performed the ultrasonography of PCVC in SVC had taken 30 cases as a training course to minimize the bias. In conclusion, ultrasonography provides an accurate and convenient method by which to assess PCVC tip location in the SVC and to help prevent serious complications that may result from malposition of PCVCs.


Parabacteroides, Alistipes, and Ruminiclostridium_5 and decreased that of Tyzzerella, Oscillibacter, Desulfovibrio, and Anaerotruncus compared with the RF and HF groups. The relative abundance of Lachnospiraceae_UCG-006 in the HFOSS group was lower than that in the HF group but higher than that in the RF group. In conclusion, OS starch prevents fat accumulation in high-fat diet-fed mice and might provide potential health benefits due to its fermentability in the gut and its ability to regulate gut microbial community structure.Effects of octenylsuccinate (OS) starch on body composition and intestinal environment in high-fat diet-fed mice were investigated. C57BL/6J mice were treated with a regular-fat (RF) diet, a high-fat (HF) diet, or a high-fat diet supplemented with OS starch (HFOSS). Fecal short-chain fatty acids (SCFAs) were quantified using gas chromatography, and the fecal microbiota profile was analyzed by 16S rDNA sequencing. One-way ANOVA and metastats analysis were performed for statistical analysis. After 22 weeks of feeding, mice in the HFOSS group had significantly lower body weight, body fat, liver weight, and cumulative food intake than those in the HF group but higher than that of the RF group. Fecal total SCFA, acetic, propionic, and butyric acid concentrations were significantly higher in the HFOSS group than that in the HF and RF groups. OS starch intervention increased the relative abundance of  Octenylsuccinate (OS) starch generally is prepared by esterification of octenylsuccinicanhydride (OSA) and starch under mild alkaline conditions ,2. OS stIn recent years, beneficial nutritional properties were reported for OS starch. Wolf et al.  found thA diet rich in saturated fatty acids is one of the major causes of obesity and related metabolic disorders ,12,13. RIt has been suggested that the digestibility of starch is reduced after OSA modification. Studies showed that OSA-modified potato, corn, cassava, waxy maize, and banana starches significantly increased the content of slowly digestible starch (SDS) and RS ,39,40,41In this study, mice were fed three different diets. For the regular-fat (RF) diet, 10% of energy was provided from fat. The HF diet had components similar to those of the RF diet but with higher energy density. The HF diet supplemented with OS starch (HFOSS) was designed to have a similar energy density as the HF diet. The energy provided by fat, protein, and carbohydrate was adjusted to be the same for the HF and HFOSS diets. Dietary fiber was derived from OS starch in the HFOSS diet and accounted for 10% (wt.%) of the total weight of the diet. In comparison, cellulose was the dietary fiber source for the RF and HF diets and accounted for 5% (wt.%) of the diet weight. The body composition of the mice was measured during the experiment. The composition of SCFAs in mouse feces was determined by gas chromatography (GC). The fecal microbiota structure was analyzed using 16S rDNA high-throughput sequencing. This study evaluated the health benefits of OS starch and revealed the impact of OS starch on fecal microbiota structure and SCFA composition in mice under the stress of a high-fat diet.v/v) was from Wuhan Servicebio Technology Co., Ltd. . All chemicals were of analytical grade, except for those mentioned specifically. Eight-week-old male C57BL/6J mice, an obesity-prone breed, were provided by Soochow University Laboratory Animal Center . A normal chow diet was provided by the Double Lion Experimental Animal Feed Technology Co., Ltd. . Experimental diets were obtained from Medicience Ltd. .Sweet potato starch was isolated by settling pureed sweet potato  in water after fiber removal. The 2-Octen-1-ylsuccinic anhydride, porcine pancreatin, and D-glucose were purchased from Sigma–Aldrich Chemical Co. . GC standards of acetic, propionic, butyric, isobutyric, valeric, and isovaleric acid were purchased from Macklin Biochemical Co., Ltd. . The 2-ethylbutyric acid was obtained from Aladdin Biochemical Technology Co., Ltd. . Insulin  was purchased from Lilly, France . The neutral formalin solution , the weight percentage of the OS group in OS starches (%OS), and reaction efficiency (RE) were determined using NMR spectrometry, as previously reported . DS, %OSMice were raised in a lab with a 12 h light/dark cycle at 24 °C and humidity of 60%. All procedures followed the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals. The experiment was approved by the Soochow University Animal Ethics Committee with an approval number of 201705A127.All mice were provided ad libitum access to a normal chow diet and water for 12 days for acclimatization. The mice were then randomly divided into three groups  and fed an RF diet (D12450J), HF diet, and HFOSS diet, respectively. From weeks 1 to 9, the HF and HFOSS diets were based on a high-fat diet of D12451 . Details of the diet are described in Every mouse was weighed weekly. The food and energy intake of mice were recorded weekly. After 22 weeks, all mice were sacrificed. The body weight, length of the mice, and the weight of liver and epididymal and perirenal adipose tissues were recorded. The Lee index, fat ratio, and liver ratio were calculated using Equations (7)–(9), respectively:W is the body weight of the mice (g), and L is the length of the mouse body from the nose to the anus (cm).e is the epididymal adipose weight (g), Wp is the perirenal adipose weight (g) of mice, and W is the body weight of mice (g).Wl is the liver weight (g), and W is the body weight of mice (g).Wg for 20 min at 4 °C . Plasma was removed and stored at −80 °C before analysis. GLP-1was measured using a GLP-1 ELISA kit .After the mice were sacrificed, blood samples were collected with an anticoagulant of heparin. Immediately after collection, blood samples were centrifuged at 3000× v/v) at 2 g/kg body weight was intraperitoneally injected into overnight-fasted mice. Before injection and 30, 60, and 120 min after injection, the blood glucose levels of mice were measured from the tail using a glucometer . The area under the curve (AUC) for glucose was estimated using the trapezoid method _fissicatena_group, and Defluviitaleaceae_UCG-011 were found in RF and HF groups but did not exist in the HFOSS group. It is also worth mentioning that cellulose was replaced by OS starch in the HFOSS group, which may affect the gut microbial diversity. Whether the metabolites of cellulose and OS starch have an across-feeding effect on bacteria is less investigated, which can be a subject for investigation in the future.ACE and Chao 1 indices were used to assess the total number of species, while Shannon and Simpson’s indices reflect the diversity of microbials. It is interesting to notice that the HFOSS group has fewer species than RF and HF groups. Supplementing resistant starch to an HF diet is not always correlated with more species in the gut ; this maPrincipal component analysis (PCA) showed that samples from the same group clustered together but were further away from samples in the other groups . A similProteobacteria and Deferribacteres in the HFOSS group were lower than those in the HF group. At the genus level, OS starch increased the relative abundance of probiotics such as Parabacteroides and Alistipes and decreased the relative abundance of pathogenic bacteria including Tyzzerella, Oscillibacter, Desulfovibrio, Anaerotruncus, and Lachnospiraceae_UCG-006 in the feces of mice fed an HF diet. OS starch intervention decreased community richness but did not change the microbial diversity indices of the fecal microbiota of HF diet-fed mice. In summary, OS starch appears to have some nutritional functions. Its health benefits may be due to its fermentability in the gut and its ability to regulate the structure of the gut microbial community.OS starch was found to prevent body fat accumulation and improve glucose and insulin tolerance in mice fed an HF diet. The body composition of the HFOSS group was similar to the RF group. OS starch suppressed the appetite of the HF diet-fed mice and increased their fecal fat secretion, which may be beneficial for body weight control. The OS starch contains a significant fraction of resistant starch, which can enter the large intestine and be fermented by gut microbes. OS starch increases fecal SCFA concentrations, especially acetic, propionic, and butyric acid, which may play a critical role in maintaining metabolic health in subjects. OS starch intervention significantly altered the fecal microbiota structure of mice fed an HF diet. The F/B ratio of mice fed an HF diet was significantly decreased by OS starch intervention, which was at a similar level as the RF group. The relative abundances of