To investigate the impact of site-specific inter-professional small-group communication skills training (CST) that incorporates critical incident approaches to learning on patient satisfaction with communication.Rehabilitation clinic specialized for spinal cord injury/disorder (SCI/D).Retrospective observational cohort study design using patient and health-professional self-report data. Data for patient satisfaction with communication were collected in 2014 (existing records) and each year from 2015 to 2021  using the MECON survey.n = 161 participants), 16 refresher (n = 84), and five short (n = 17) CST seminars were conducted. Overall, 262 employees  participated; 92 participants (response rate 37.6%) responded to feedback surveys. They rated the seminars positive concerning the alternation between theory, discussion, and practical exercise in 91.3%, and rated the length of the training ideal in 80.2%. Post-program patient satisfaction overall increased from 83.1%  2.6%) to 90% . It was higher in specific communication-related topics: “receiving information” , “being able to bring in concerns”  and “being treated with respect” .Fifteen basic (Inter-professional CST is feasible and well accepted by professionals from various professional groups. During seven years of continuous training, independent patient ratings of satisfaction with professional communication have improved significantly. Participants attest to the training's high credibility and usefulness in everyday life. Communication in medical rehabilitation is widely accepted as a prerequisite for patient-centered care and collaboration among health care professionals (HCP). A core element of patient-centered care is HCP's genuine interest in patients' perspectives. Although there are different theoretical models of patient-centered communication (PCC), the core element of PCC shared by most authors is best described as: “PCC is a mixture of technical skills and health care providers' attitude that helps elicit the patients' perspective” –3. To inFor many years now, communication skills training (CST) has become a standard element of HCP student education –6. HowevDifferent approaches are used in implementing CST: a recent initiative in Denmark , 11 deliCommunication skills training in settings for patients with spinal cord injury/ disorder (SCI/D) was largely ineffective –15, but Effective communication is essential in acute and rehabilitation services for people with SCI/D. These people are in extremely challenging situations: their future prospects have changed fundamentally and they have to develop a completely new body image . They muTo address these topics effectively, HCP need a patient-centered approach to communication. In the primary care context, this has been described as “inviting the patient's perspective” . In the When setting up a CST in this clinical setting, the unique characteristics of a rehabilitation clinic should be considered. HCP and patients with SCI/D work together over a long period of time, often lasting more than half a year. During this time, they must come to terms with acute SCI/D-related complications, such as pressure injuries and problems with bladder and bowel management. This is in stark contrast to a more common hospital setting, where acute problems are treated within a few days. In such an environment, professionals do not need to build a lasting relationship with patients and relatives; rather, the achievement of long-term goals takes place outside the hospital and in an outpatient setting. In a rehabilitation setting, many professional groups cooperate to help patients adapt and improve their well-being and functioning; this requires extensive inter-professional communication, e.g., between nurses, occupational therapists, physiotherapists, psychologists, social workers, physicians from different specialties, peer patients, etc. . Thus, iThis study aimed to investigate the impact of site-specific inter-professional small-group CST on satisfaction with communication in people with SCI/D. It was also interesting to see if such training was equally well accepted by different professional groups; therefore, participant feedback was used as a secondary outcome.Retrospective observational study using regularly administered participant feedback and patient satisfaction surveys in a single rehabilitation clinic. The study was conducted as an institution-wide intervention and was part of a quality improvement project. The Ethics Committee Northwest and Central Switzerland (EKNZ) confirmed that the research project met the general and scientific standard for research involving human subjects (AO_2022-0017). The reporting of the study followed the STROBE criteria .This project took place in a comprehensive tertiary rehabilitation center  that specialized in the treatment of people with an acute or chronic SCI/D. The clinic had 160 beds for the acute care and rehabilitation of patients with SCI/D, including an intensive care unit with eight beds. In 2021, the clinic employed about 1,500 people, the staff of those who have regular patient contact consisted of about 70 physicians, 300 nurses, 49 physiotherapists, and 31 occupational therapists. Since the clinic's founding in 1990, it had implemented a “holistic” treatment approach that combined inter-professional teams, spinal cord injury research, post-graduate training, a sports facility, and technical support for the specific needs of people with SCI/D. Since 2006, the clinic had used the International Classification of Functioning Disability and Health (ICF) to define rehabilitation goals and barriers within a bio-psycho-social model. As part of the continuous education of HCP, the clinic offered mandatory advanced life support courses and various voluntary courses on non-violent communication, leadership, and how to create a living will. Apart from the required quality criteria for SW!SS REHA or ISO 9002 certification, there were no specific communication guidelines or concepts.The project started in 2014 when the hospital's administrative board decided to respond to unsatisfactory feedback from patients on various aspects of communication. To identify “hot spots” where changes in attitudes or structural deficits were likely to improve communication, the administrative board invited a well-known Swiss clinical communication expert (WL) to perform a situation analysis. Instead of standardized questionnaires or observation grids, he proposed “shadowing” members of different professional teams and observing their communication in different clinical situations. A report described his observations during ward rounds, inter-professional meetings with patients and relatives, and team meetings. This report included observations at the structural level, such as the professionals were not properly introduced during activity assessments, the role of a moderator was not defined, and the patient perspective was not systematically elicited. Similarly, during the ward-rounds patients were not systematically invited to contribute to the definition of short-term treatment goals, their emotions were sometimes ignored, etc. Information was not checked for correct understanding, and the technique of “teach back” was scarce. In general, observations revealed low patient and relative engagement in inter-professional rounds and an apparent lack of shared understanding of the patient's situation. This report substantiated the critical feedback from patients and relatives . It was discussed by the hospital's administrative board, which decided in 2015 to implement CST that would address these issues.At the institutional level, a steering committee was established that included representatives from all medical disciplines and professions. It met four to six times a year, supervised the progress of implementation and reported it to the head manager. The first step was to develop an institutional concept, which was discussed and approved by all different professional groups. Access to training, intensity and frequency of training, number of participants, etc. were defined, and training materials were adapted to the different training formats. The information of the staff about the intervention, the sending of invitation and reminder e-mails, and the collection of feedback data were taken over by the leader of the steering committee  and the human resources department.According to the institutional communication concept, all HCP who were senior members of inter-professional teams with direct patient contact were invited to participate. The recruitment process was mandatory for certain professional groups, mainly senior members of different professional groups. Team-specific workload and flexibility were considered to ensure continuous participation throughout the whole observation period. Overall, staff turnover rates had been comparably low with 9.4% in 2015, 8.1% in 2016, and 11.3% in 2021 (numbers provided by the human resources department). Attrition differed by participant status: while almost all senior team members retained their role during the observation period, junior doctors spent between 1 and 2 years as residents before moving to another training hospital.The annual surveys were part of routine quality assurance, and discharged patients could choose whether or not to complete these surveys as volunteers. Data for this study were extracted from standard MECON items. These surveys were financed by the hospital and sent by a neutral and official organization (MECON). These surveys included general questions about satisfaction with care, organization, and communication. No reference to this CST was mentioned.The CST is based on a well-established CST of the University Hospital Basel , 33–35 iAfter the AS-S attended a 2.5-day “train the trainer” seminar at another institution  led by WL, AS-S and WL held the seminars together. They lasted 8 h and included between 8 and 12 participants. A refresher course was offered about 2 years after the initial seminar; it lasted 4 h and focused on problems participants had encountered in applying newly acquired communication skills.The seminars started with explicit information about the agenda and time structure. Confidentiality issues were addressed at the beginning of each seminar, and the content of the seminar was covered by the rules of medical confidentiality that apply to all hospital employees and are part of their contract. Individuals mentioned in critical incident reports were not referred to by their real names and were described in as little detail as possible. Waiting, echoing, mirroring, and summarizing , 37 were“Critical Incident Protocols” (CIP) were used, linking participants' everyday experiences of difficult communication to the content of the seminar. After participants completed their CIP (which took approximately 10 min), the following three-step procedure was applied :Produce shortened verbatim protocols of participant CIPs on flip-chart.Identify teachable moments  that helApply communication techniques in role-play sessions between participants based on the respective CIP.Depending on the professional background, critical incidents referred to communication with patients or relatives or with other professionals. The seminars offered a combination of learner-centered elements (starting from problem cases of the participants) and trainer-centered inputs (information segments on communication techniques and facilitation during role-plays) that mimic encounters between patients and HCP. Exactly the same elements can be found in daily clinical management: listening to the patient's perspective, sharing information, and accompanying patients and relatives in the rehabilitation process.The format of the on-the-job feedback was not strictly defined: some participants requested feedback on a specific skill they wanted to use, and others were interested “in anything you find interesting to me.” AS-S and WL shared their observations and decided whether to bring the topics to the steering committee. When the results of the on-the-job feedback were discussed outside the trainer dyad, neither the names nor the working place of the participants was mentioned.Participation in the CST was voluntary in the first year (2015) to assess the feasibility and acceptance of the intervention. When feedback from participants was positive, the steering committee discussed whether participation should become mandatory and decided against this option. However, in two cases, the courses were mandatory: first, when a professional group (primarily senior consultants and senior physiotherapists) decided on its own initiative that all of its members should attend a seminar, this was accepted by the steering committee. Second, when participants developed communication standards within their professional group , these standards became mandatory after thorough discussions and acceptance by the steering committee and among the professional groups involved.Implementation data were collected using the institutional data provided to the steering committee, including the number of training, the number of participants, and the time invested.via e-mail a couple of days after the training.The CST sessions were evaluated by the HCP using a questionnaire developed by the human resources department for evaluating seminars . It was Patient satisfaction was assessed using a standard survey provided by an external company  were organized. One “train the trainer” course was conducted in 2019 with the goal of training steering committee members to become communication trainers. These eight participants, mainly members of the communication steering committee, were recruited at least 2 years after their participation in the actual CST.In 2015 and 2021, the clinic employed 1,142 and 1,445 HCP, respectively. A total of 262 employees participated in one of the training sessions: 161 participants in the basic training, 84 participants in the refresher training sessions, and 17 participants in the short training sessions . ParticiThe time investment between 2015 and 2020 can be calculated as the sum of participation time (161 full-day seminars of 8.5 hours each) plus 84 half-day seminars of 4 h each, plus steering committee meetings. A total of 250.4 days were spent by participants, 47 days by two trainers , and 12 days on on-the-job training . A totalOverall, 37.6% (92/262 participants) provided structured feedback, 38.5% (62/161 participants) in the basic training, and 35.7% (30/84 participants) in the refresher courses. The distribution between theory, discussion, and practical exercise was rated positively by 91.3 % of participants in both the basic training sessions (88.7%) and the refresher courses (96.7%). The duration of the trainings was rated as ideal by 80.2% . The professional competence was rated as absolutely competent and practical 90.1% . Approximately, 32.2% of participants responded that they achieved all learning goals  or the greater part of their learning goals, 52.2% . They rated the content extremely positive and were determined to apply it, 38.6% , or motivated to apply it, 44.3% . The participants responded that the quality of their work had noticeably improved, 44.7% , and that they could recommend the seminar to others, 98.8% . A few participants gave negative feedback concerning the duration being too short, 16.5%, or too long, 3.3%, not achieving the learning goals, 1.1%, the content, 1.1%, lack of motivation to apply the content, 1.1%, or the insecurity in applying the newly acquired tasks, 3.5%  .2 = 0.776; p = 0.004), for “receiving information” to 90.2% . Satisfaction with “being able to bring in concerns” had increased to 90.8%  and “being treated with respect and dignity” to 94.4%  (Standard surveys (MECON) yielded the following results : in 2014, patients rated “satisfaction in general”with 83.1% (CI 2.6%), “receiving information” with 81.1% (CI 3.1%), “being able to bring in concerns” with 83.0% (CI 3.1%), and “being treated with respect” with 89.4% (CI 2.6%)  . Annual = 0.004) .Based on the experts' feedback, different professional groups started refining their clinical practice: nurses and physicians developed a standard procedure for clinical ward-rounds, and inter-professional group of therapists, nurses, peer patients, and physicians developed a new standard for the assessment of patient activities . In applIn the course of the intervention, word spread that communication was an issue at the institution and that discussing communication issues with the expert had helped others. This encouraged other professionals to ask for support with their specific communication challenges. Usually, a representative of the respective group reached out to AS-S. Specific training sessions with a well-defined focus were developed for some of these employees who had not been invited to participate in the CST initially. For example, hotel service staff argued that they also had patient contact and would therefore benefit from specific training. Secretarial staff at the outpatient reception desk wanted support in dealing with demanding patients or relatives. Peer counselors wanted coaching on their self-awareness, culminating in a standard for presentation to in-house patients. Specialized seminars were also offered to the facility services team, the intensive care unit nursing team, and the psychology team, and the outpatient clinic administrative team requested additional meetings.Therapists, nurses, and physicians suggested producing educational videos on good communication practices to be shown to new team members or to use in in-house presentations or at professional meetings.We report 6 years of experience with an inter-professional small-group CST. It proved feasible and acceptable and had a positive impact on patients' evaluation of service experience in each year of implementation and HCP's evaluation of learning experiences. It required coordination by experts at multiple levels, structural coordination by a steering committee, and the use of institutional data already collected for workforce reporting, patient satisfaction and staff planning. The program was embedded in an institutional environment that supported in-house continuous professional development through release time, “train the trainer” opportunities, investment in specialist expertise, alignment with institutional quality system goals, and access to institutional data on staff and patients.Participant feedback showed that the intervention was useful in daily practice and provided a balance between learner-centered principles and tutor input and between practice and theory. Patient surveys showed a sustained positive effect on the perceived quality of communication.Since we did not compare different means of implementing the communication skills intervention, we rely on informal comments from participants and stakeholders. We believe that the following aspects were important for the success of the implementation process.The credibility of the intervention improved by the fact that it was initiated by data from an independent and trusted organization outside the institution.When this external source-reported deficits in patient satisfaction with communication the hospital's administrative board decided to commit to an institution-wide effort to invest in these critical domains. Besides in-house capacities [continuous professional development ], supporThe format of CST and feedback on-the-job was flexible, thus responsive to the emerging needs of clinic members during the course of the intervention.Although different training formats required a different balance of these elements, the explicit pedagogy remained the same: rapid-cycle deliberate feedback, participant-generated CIP, and a confidential small-group environment. We assume that the use of CIP helped to ensure practicality, participant problems were addressed rather than problems derived from the literature . The useOn-the-job feedback allowed tutors to see learners in action and gain insight into the feasibility of learning objectives in a clinical context.It takes a long breath to change the culture within an institution and to realize the benefits of such an institution-wide approach. Resistance was a common phenomenon, especially in the early stages. Mutual support among tutors and within the steering committee helped to keep on going, remain calm and keep a positive stance, and remain humble even in the face of reluctant or dismissive colleagues , that isSince this observational study targeted representatives of many professional groups and was open to new professional groups if they requested training themselves, a structured situational analysis of communication skills and inter-professional communication culture was not possible.Another critical point is the low response rate to the feedback questionnaire. This may have introduced bias in that more satisfied patients were more likely to take the time to indicate their satisfaction with various aspects of their hospital stay. However, even if that were the case, it would be a systematic error, which applies to all data points in the time series of observations. In general, data show that satisfaction surveys are sensitive to changes in the hospital environment, as suggested by Otani et al. , 49: theApparently, participants perceived tutors as trustworthy. This might limit the transfer from our intervention to other settings. We assume that the credibility of tutors was supported by their clinical and theoretical expertise . We are aware that working with CIPs requires an enormous flexibility from the tutors. They were never sure, which mix of problems would be presented during a seminar and had to adapt “on the fly” to the needs of the participants. This was the main reason why participants in the “train the trainer” course did not feel competent enough to conduct courses in a similar manner. Future developments should probably take these high demands into account and consider a slightly modified approach to conducting seminars.A fundamental criticism might relate to the lack of behavioral measures for improved communication competence. As we argued in an editorial on articles describing interventions in the field of “breaking bad news,”  there isIn contrast to recent intervention studies, we did not report changes only in the group of “extremely satisfied” patients . InsteadSmall-group, site-specific inter-professional CST in the acute care and rehabilitation context was feasible, and it made a difference for patients who attested to improved communication in patient satisfaction surveys. Integration in an institutional-wide change process, supported by the administrative board and participants' centered training sessions combined with feedback-on-the-job, seem to be factors for success.www.mecon.ch]; as company data they are not available. MECON agreed to have the dataset published. The critical incident protocols were deleted following data analysis in accord with the ethic approval.Participant training feedback data are stored with the corresponding author in institutional records in a clinical medium. Anonymized patient satisfaction surveys are stored at MECON [The studies involving human participants were reviewed and approved by Ethical Committee North West Switzerland (EKNZ AO_2022-00017). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.AS-S, WL, PL, and DS-N were responsible for the implementation of the intervention. AS-S, SE, MS, and WL performed data analysis. MS performed the statistical analyses of the patient survey data. LJ and DS-N supported the intervention as representatives of the management board and guaranteed institutional integrity. AS-S, SE, and WL wrote the first draft. All authors made substantial contributions to study conception, data collection, interpretation of results, gave critical feedback to several versions of the manuscript, read, and approved the final version.No funding was received externally. The MECON survey was financed through the quality management department of the clinic. The external specialist (WL) was financed through the human resource department of the clinic as part of the employees' continuous training program. The participation of all HCP was arranged and financed through their specific departments.Author MS was employed by MECON Measure and Consult GmbH.The remaining 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.The authors of the study were also engaged in the steering committee of the intervention. Even when the results (participants feedback and patients surveys) are independent of the authors the presentation of the study might be biased.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.


Multiagent chemotherapy offers an undoubted therapeutic benefit to cancer patients, but is also associated with chronic complications in survivors. Osteoporosis affects the quality of life of oncologic patients, especially at the paediatric age. However, very few studies have described the extent of loss of bone mineral density (BMD) in bone sarcoma patients. We analysed a retrospective series of children and adolescents with primary malignant bone tumours (52 osteosarcoma and 31 Ewing sarcoma) and retrieved their BMD at diagnosis and follow-up as Hounsfield units (HU). We studied their individual BMD trajectories before and after chemotherapy up to 5 years, using routine chest CT scan and attenuation thresholds on T12 vertebrae ROI. At one year, bone sarcoma patients showed significant bone loss compared to diagnosis: 17.6% and 17.1% less for OS and EW, respectively. Furthermore, a bone loss of more than 49.2 HU at one-year follow-up was predictive of the persistence of a reduced bone mass over the following 4 years, especially in patients with EW. At 4 years, only 26% and 12.5% of OS and EW, respectively, had recovered or improved their BMD with respect to the onset, suggesting a risk of developing morbidities related to a low BMD in those subjects. Standard chemotherapy offers an important therapeutic benefit in cancer patients, but at the same time can be responsible for late complications in survivors, requiring additional therapies or preventive strategies. Among the long-term medication-induced adverse effects, a reduction in bone mineral density (BMD), known as secondary osteoporosis, may be detected ,2. In prOsteosarcoma (OS) is the most frequent primary malignant bone tumour (8–11/million/year) with a peak incidence at 15–19 years of age . In bothAlthough there is solid evidence on the development of secondary osteoporosis in long-term survivors of bone sarcomas, this is still a neglected field of investigation ,17. In pIn 2018, the Children’s Oncology Group (COG) published guidelines for long-term follow-up of childhood, adolescent, and young cancer survivors, recommending BMD assessment by DXA at 2 ys after completion of therapy only for patients treated with methotrexate [In this study, we opportunistically analysed a retrospective cases series of primary bone tumours (OS and ES) for whom BMD data were retrieved at the clinical onset, during and after treatment up to 5 years after the end of therapy, thus analysing individual trajectories in a thorough manner in order to ascertain the effect of chemotherapy on bone health and to identify patients at higher risk of developing secondary osteoporosis.We retrospectively analysed a continuous series of 168 patients with OS and 88 with EW, treated at our Institution between May 2007 and December 2009. Patients here considered were not treated with the randomized EuroEWING2012  and OS2006  protocols in which zoledronate was evaluated for its presumptive anticancer activity. All patients underwent routine chest CT scan at diagnosis and during their follow-up for staging. Inclusion criteria: patients were examined with the same CT scanner  and the same acquisition protocol (120 kV scan and slice thickness of 3.75 mm) at diagnosis and during the subsequent 5 y follow-up. Exclusion criteria: age over 45 ys, presence of other conditions that could affect bone metabolism, diseases involving the spine or conditions that could cause significant CT image artefacts . Based on the exclusion and inclusion criteria, 52 patients with OS and 31 with EW were included from those initially considered. Six age-matched children and adolescents undergoing CT examination for spine trauma in our hospital were considered as control. The study was approved by the local Ethics Committee (CE-AVEC 434/2019/Oss/IOR). OS patients received standard treatment consisting of preoperative multiagent chemotherapy, surgical excision, and postoperative chemotherapy according to standard protocols. EW patients were treated with the combination of pre- and postoperative chemotherapy plus radiotherapy vs. surgery as local control. Fourteen high-risk EW patients received high-dose chemotherapy (HDCT) followed by autologous peripheral blood stem cell transplantation (ASCT) for disease relapse or progression. The patient characteristics are summarized in To retrospectively obtain a surrogate measure of trabecular BMD, we used a method based on the measurement of a region of interest (ROI) of the acquired CT scan. This method has been validated by the comparison with DXA T-score for the assessment of osteoporosis . We usedT0–T1) of the combined populations of OS and EW patients as a cut-off value. This value corresponded to −49.23 HU. An AUC above 0.8 provides convincing prognostic evidence (excellent when above 0.9), while those below 0.8 provide fair/bad prognostic evidence [p-values < 0.05 were considered statistically significant. Statistical analyses were performed with GraphPad Prism 7  for all but one test: for the ROC curve analysis, we used MedCalc Software . Due to the small number of observations, data were not considered as normally distributed and nonparametric tests were used. To test the difference between two groups we used the Mann–Whitney U test , and the Wilcoxon test . To test correlation, the Spearman rank test (two-tailed) was used. For the evaluation of the association between BMD ROI attenuation values at T0 and the risk of relapse, we considered only a subgroup of patients without the presence of clinically evident metastases at diagnosis . For the analysis of sensitivity and specificity in predicting the occurrence of long-term BMD decreased in bone sarcoma survivors and for plotting the receiver operating characteristic (ROC) curve, we used the 70th percentile of the differences between the CT attenuation value at T0 in respect to T1  for OS and 225.65 HU (min–max 158.13–321.31 HU) for EW. We found no significant difference in BMD between OS and EW groups, nor between cancer patients and controls A. p = 0.0433). In our series, 17% of OS and 23% of EW patients had clinically evident lung metastases already at the disease onset (p = 0.0219).Furthermore, we found no correlation between BMD and tumour localization (data not shown), or with gender in EW patients, whereas in OS females showed a higher BMD than males . In T1–T0) was detected between OS and EW patients.Already after around 1 year from the onset (T1), upon completion of the treatment protocol, both OS and EW patients showed a significant reduction in BMD, as assessed by the attenuation of CT ROI . Finally, the extent of BMD loss immediately after treatment was significantly and inversely correlated with patient age (p = 0.0105). This correlation became even more evident when we considered the percentage of bone loss over time with respect to the individual patient, comparing the BMD value at T1 with the respective value at T0 (p = 0.0021). Finally, we did not observe any correlation between the magnitude of BMD reduction and the gender . However, this difference completely flattened out when we considered the reduction in BMD according to the individual patient’s trajectory of HU value . Finally, in EW patients only, when we compared the BMD value of the patient group at a one-year follow-up, we found that the use of radiotherapy had a negative impact on bone health  to show that the results were almost the same, even when the intrapatient BMD decrease was considered. In contrast, in OS patients, BMD was almost completely restored  (p < 0.0001). Notably, regardless of the type of bone sarcoma, the patient’s age at tumour diagnosis was significantly and inversely correlated with the patient’s BMD recovery (p = 0.0183). Note that in our groups, EW patients are slightly older that OS patients  developed lung metastases during their follow-up, and 16 patients  underwent thoracic surgery. In addition, 13 patients had a local recurrence . Consequently, only 14 and 10 patients could be censored for OS and EW at the last follow-up, respectively . Howeverpatients . Since tpatients D.In order to study the risk of developing permanent bone loss based on specific clinical and personalized characteristics, it is crucial to consider the individual BMD trajectory. We thus assessed the ROI attenuation value of each individual over time and found that the most severe loss of BMD occurred shortly after one year, which is usually the time of completion of the treatment protocol at T1, A,B. T1–T0 below the cut-off value were highlighted in red. From the graph, it is clear that patients marked in red did not return to the original BMD level, even 5 years after diagnosis. Sensitivity and sensibility were analysed and confirmed using the likelihood ratio test (predictive performance)   and ROC In this study, we opportunistically collected chest CT scan data to determine the disease-associated or drug-induced BMD loss in a homogeneous series of OS and EW patients by considering individual BMD trajectory. We also investigated whether, at one year after tumour onset, the extent of BMD loss was related to the persistence of abnormal low BMD in the long term. To achieve this goal, we used the HU value, obtained from CT scans and CT attenuation thresholds, as a surrogate marker of BMD, as previously validated by the comparison with DXA measurements, with the specific aim of distinguishing osteoporosis from non-osteoporosis ,27. We dAt the onset, BMD values were not affected, as revealed by the comparison with a small group of non-oncologic subjects. Furthermore, in contrast to the data presented by Ruza et al. , we founAfter one year, BMD tended to be lower than in the control group, corroborating the evidence of previous studies on a larger cohort ,35, evenLoss of BMD at this stage of treatment could be due to several factors: first and foremost, the toxicity of polychemotherapy on bone, but also the reduced physical activity during treatment and frequent immobilization due to surgery, and the consequent decrease in muscle mass and vitamin D. In OS, two or more drugs are usually given together: the high-dose regimen of methotrexate, doxorubicin, and cisplatin (MAP regimen) is the most common first-line chemotherapy, although ifosfamide and etoposide are added in patients with poor response . The mosMeasuring BMD at clinical remission, Ruza et al. found that lumbar BMD in pubertal patients with OS and EW tended to be lower than that of patients who had completed pubertal development at the time of diagnosis . HoweverWe then considered the risk of failure to regain bone health even after several years (4–5 years after the onset) in survivors and its correlation with clinical characteristics. Again, our data were in contrast to previous findings showing that a high bone growth rate at prepubertal and pubertal age is a negative prognostic factor for long-term bone health outcome in patients with bone sarcoma undergoing chemotherapy . In factOur study has some limitations, including the small size of the OS and EW groups, the retrospective study design, and the lack of information on other markers/factors related to bone remodelling  that could reduce BMD. These, however, cannot be retrieved in a retrospective analysis. Furthermore, the number of cases was reduced to include only data from a single scanner and a single scanning protocol in order to limit the variability of HU measurements. For future studies, the bone density measurement protocol that relies on measuring data from a single CT slice, using an operator-chosen ROI , can be In this work, we confirmed an increased risk of bone loss in bone sarcoma survivors, especially in EW patients, and provided novel findings that highlight the importance of studying individual trajectories to verify treatment-induced bone loss in each individual patient, according to a personalized approach. Indeed, the growth rate of bone volume has a defined and common pattern during human development, with the peak of bone growth occurring during puberty, which is also the most frequent period of bone sarcoma development. However, the rates of bone growth and BMD value in the spine at a specific age are strongly influenced by numerous factors that vary considerably among individuals, including race, gender, genetic factors, physical activity, calcium and protein intakes, weight, age of menarche, poor nutritional status, and a delayed onset of puberty ,48.This individual perspective paves the way for the identification of patients at risk of developing morbidities related to abnormal early bone loss, such as osteoporosis and increased fracture risk. This type of analysis can be performed by comparing CT analysis at the onset and at one-year follow-up. The use of the chest CT scan is already standard in these patients, and therefore does not require additional time, cost, or radiation exposure. This method may significantly impact on the long-term quality of life of bone sarcoma survivors: it allows for early preventive intervention aimed at avoiding the development of secondary osteoporosis, with specific recommendations, as suggested by the COG . Regarding the use of bisphosphonates, OS2006 and EuroEwing2012 clinical trials included the use of zoledronate in combination with chemotherapy ,50. HoweIn conclusion, the use of CT analysis to assess the extent of bone loss and validate the cut-off value of BMD loss at one-year follow-up to predict the risk of irreversible bone loss in patients with bone sarcoma deserves further investigation, including through prospective longitudinal ad hoc studies.


Information technologies have become indispensable in the office environment with a considerable increase in the use of computers. Musculoskeletal complaints in computer workers have a multifactorial etiology; therefore, an ergonomic investigation should be based on both self-reporting of symptoms and quantifiable observational methods.This study aimed to evaluate ergonomic and biomechanical characteristics of computer workers to identify the presence of symptoms and to assess the existence of a correlation between experts’ observational assessment and workers’ self-perception.Participants were approached by an observer responsible for screening of symptoms and demographic characteristics. Volunteers were then evaluated simultaneously by two blinded observers.Seventy-one computer workers participated, and no significant differences were observed for duration of work on a computer between participants with and without pain. Interobserver reliability was good . No correlation was found between Maastricht Upper Extremity Questionnaire and Rapid Office Strain Assessment scores (p = 0.054/r = 0.230). There was no difference between participants with and without pain in the Rapid Office Strain Assessment (p = 0.931). In the Maastricht Upper Extremity Questionnaire assessment, there were differences in job demand (p = 0.004), complaints (p = 0.034), and total score (p = 0.044), with higher scores for asymptomatic participants.The results suggest that asymptomatic individuals are subject to higher job demands probably because they have not previously experienced significant pain. However, they have other complaints, such as stiffness, disability, weakness, edema, and paresthesia. Symptomatic individuals, in turn, have greater trouble in aspects such as reduced amount of time spent on work and performance of work requiring extra effort. This demonstrates that increased use of technologies at work has come at the cost of workers’ well-being.Increased use of computers stems from economic development in recent decades, which led to organizations using more computerization systems and devices to improve the productivity of their workers.6 There are also psychosocial factors related to work, such as time pressure, lack of social support, and poor job satisfaction, which may contribute to the development of work-related musculoskeletal disorders (WMSDs).6Workplace risk factors that may cause changes in the health of computer workers correspond to the physical demands imposed by performing their activities, including the postures adopted to perform job duties , the applied force, the duration of tasks, and the frequency and repetition of movements.7 neck and head,8 and spine.9 Musculoskeletal complaints among computer workers have a multifactorial etiology,10 and the main causes include poor postures, bad habits at work, workstation design, and psychosocial factors.5 Among these multiple factors, biomechanical 11 and lifestyle  characteristics are noteworthy.12The main musculoskeletal disorders associated with computer work affect the upper extremities,13 This technique is advantageous because different aspects are analyzed considering the individual’s self-perception. It is also economically feasible and quick to administer, which makes it a large-scale approach.14In the field of ergonomics, the most used method to investigate the influence of biomechanical, ergonomic, and psychosocial variables on musculoskeletal disorders is based on self-reporting of symptoms.15 Thus, an alternative way to provide more reliable data on working conditions is to combine self-report instruments with preferably quantifiable observational methods, such as checklists, which can be completed directly (in loco observation) or indirectly (image recordings).15The main disadvantages of using self-report instruments are possible inaccuracies and/or unreliability of reports as well as individual differences in the levels of education, understanding, and interpretation.16 is one of a few tools in the scientific literature to assess the workers’ self-perception of ergonomic and psychosocial aspects, being specific for computer workers. The Rapid Office Strain Assessment (ROSA), in turn, is a checklist used for assessing postures of computer workers in the office environment.17 Unlike the MUEQ tool, the ROSA checklist is intended to assess postures through experts’ observation. ROSA was designed to quantify musculoskeletal risks in different postures, with good levels of sensitivity (76%), specificity (68%), and interobserver reliability.18The Maastricht Upper Extremity Questionnaire (MUEQ)19 The generally affected health categories are physical, social, and emotional functions as well as self-perceived health and well-being,20 which can all be measured by the Medical Outcomes Short-Form Health Survey (SF-36).21Researchers have given increasing attention to issues related to workers’ health status and quality of life.22 The authors reported a lack of ergonomic studies and the need for an observational assessment of workstations, reinforcing that this should not be based on self-reporting only.22A systematic review of cohort studies found limited evidence that irregular body posture, poor computer skills, distance of keyboard from edge of the table less than 15 cm, high task difficulty, low job control, and perceived muscular tension are associated with the development of musculoskeletal pain.Thus, this study aimed to evaluate ergonomic and biomechanical characteristics of computer office workers at a private institution and to identify the presence of symptoms. It also investigated the degree of correlation between the ROSA observational assessment of biomechanical and ergonomic factors and the MUEQ self-perception assessment of workstations and body postures.16 and SF-3621 questionnaires. Volunteers who met the eligibility criteria were then visited by two new observers (O2 and O3), blinded to demographic characteristics and symptoms of the participants. These two observers performed an individual but simultaneous assessment of the workstations (ROSA checklist).17 Importantly, O2 was not aware of the assessment of O3, and vice versa. The study was approved by the Research Ethics Committee at Universidade de Araraquara (CAAE No. 60154916.6.0000.5383) in accordance with the standards established by the Brazilian National Health Council Resolution No. 466/12. All individuals who agreed to participate signed an informed consent form.The participants were initially approached by an observer (O1) who was responsible for conducting the screening process containing demographic questions and for distributing the MUEQ-Br18The study sample consisted of computer office workers at a private university. They were aged 18 to 50 years, had the same job for at least 12 months, and performed at least 4 hours of computer work per day.Those who were illiterate, those with a cognitive deficit, visual impairment (not corrected by glasses), hearing loss (not corrected by hearing aids), or diseases causing intellectual impairment, those with a history of fracture, dislocation, and/or surgery in the upper extremities, head, and spine, and those with systemic disorders  were excluded.23 was used to identify symptomatic participants and to determine pain severity. This is an 11-point scale ranging from 0 (“no pain”) to 10 (“pain as bad as could be”).For characterization of the participants, a pain numerical rating scale24 which is a generic quality-of-life instrument that is easy to understand and administer. It has eight components: physical functioning, limitations due to physical problems, pain, general health perception, vitality, social functioning, limitations due to emotional problems, and mental health. There are 36 items with a total score ranging from 0 to 100 points. This system was developed so that the highest score (100) indicates best health status and 0 corresponds to worst health status.In addition, self-perceived health status was assessed with the SF-36,17 and the MUEQ self-report tool16 were used to assess ergonomic and biomechanical aspects. These two approaches were compared and, to ensure that the observers’ assessment was reliable, the reproducibility of ROSA was carried out by two blinded observers.The ROSA checklist16 is a tool available for assessment of ergonomic and psychosocial aspects, being specific for computer workers. Also, the tool was developed to characterize in detail complaints of the arm, neck, and shoulder (CANS).10 The revised MUEQ-Br has 41 questions divided into six domains: workstation, body posture, job control, job demand, break time, and social support.16The MUEQ16The domains are scored as follows: workstation - six questions referring to aims and physical space, with a maximum score of 7 points; body posture - six questions referring to body position, with a maximum score of 18 points; job control - nine questions referring to self-management, with a maximum score of 27 points; job demand - seven questions referring to work pressure, with a maximum score of 21 points; break time - six questions referring to duration of breaks, with a maximum score of 18 points; social support - seven questions referring to work routine, with a maximum score of 21 points. It also includes complaint items to characterize the CANS.17ROSA is an ergonomic checklist designed to quantify exposure to musculoskeletal risk factors in different postures of computer workers in the office environment. ROSA is based on other checklists and aims to identify the degree of ergonomic risk using specific scores. The Brazilian Portuguese version was validated by Rodrigues et al.ROSA is based on a visual assessment of individuals at their workstations. Thus, the observer will select the observed postures as well as the time spent to perform that task while maintaining a specific posture. ROSA is divided into three sections  - A assesses posture in the chair, B assesses position of the monitor and telephone, and C assesses position of the keyboard and mouse. Finally, scoring charts are used to calculate a final score ranging from 0 to 10.18 demonstrated a correlation between higher levels of discomfort and increased ROSA scores. The final score is used to assign the observed posture to an action level, indicating the recommended intervention. The four action levels are: level 1 (scores 1 and 2) - posture is acceptable if not maintained and repeated over a long period; level 2 (scores 3 and 4) - further investigation is needed; level 3 (scores 5 and 6) - further investigation and changes are required soon; and level 4 (scores 7 or over) - investigation and changes are required immediately.Sonne et al.The results obtained were submitted to basic descriptive statistical procedures, and the variables were described with mean, standard deviation (SD), and 95% confidence interval (95%CI). The significance level was set at 0.05. Data distribution was assessed by the Shapiro-Wilk test, and equality of variances, by the Levene test. For data with a normal behavior, the Student t-test was used. For those with a non-normal behavior, the nonparametric Mann-Whitney test was used with a significance level of 0.05.25The correlation of MUEQ workstation domain, body posture domain, and total scores with ROSA total scores was assessed with Spearman rank correlation coefficient (rs). The correlation was rated as strong (rs = 0.70), moderate (rs = 0.40 or rs < 0.70), or weak (rs < 0.40), with a significance level of 0.05.26Intraclass correlation coefficient (ICC) and its respective 95%CI were used for statistical analysis of reproducibility. The ICC is interpreted as follows: less than 0.40 - poor reproducibility; between 0.40 and 0.70 - moderate reproducibility; greater than 0.75 - good reproducibility.Seventy-one computer workers participated in this study. No significant differences were observed for anthropometric data and duration of work on a computer between participants with and without pain . However26 The correlation analysis between ROSA total scores and MUEQ workstation and body posture domain scores was not significant ; when the sample was divided by presence or absence of pain, the ICC was 0.91 (95%CI 0.84-0.95) for symptomatic participants and 0.96 (95%CI 0.90-0.98) for asymptomatic participants, demonstrating good reliability.nificant .No difference in ROSA total scores was observed between symptomatic and asymptomatic participants; however, an analysis of MUEQ domain scores showed differences in job demand (p = 0.004), complaints (p = 0.034), and total score (p = 0.044), with higher scores for asymptomatic participants . It is wBased on the characteristics presented by the study sample, how individuals with pain interpreted their limitations due to physical and social aspects differed from that of those without pain. Symptomatic participants reported greater trouble in SF-36 items addressing topics such as cutting down the amount of time spent on work or other activities and having difficulty performing work or other activities and taking extra effort. In line with these findings, concerning the MUEQ job demand domain, which includes questions about working under extensive pressure, working extra hours to finish tasks, and speeding to finish tasks on time, asymptomatic participants were found to be subject to higher job demands.16There was no difference between the groups with and without pain regarding ROSA total scores and MUEQ domain scores, except for job demand and complaints; therefore, the physical aspects of the workstation were not associated with pain. It is assumed that participants without pain are subject to a higher job demand than those with pain, which may have influenced the higher score in the complaint items and, consequently, the MUEQ total score. Importantly, the MUEQ complaint items address not only presence of pain but also other complaints, such as weakness, stiffness, disability, edema, and paresthesia. Also, other authors suggest that these items should only be used to characterize the sample and symptoms, and should not be scored and used for analyses such as the one in the present study.2 Regarding mean scores in the observational assessment of the present study, the action level for workstation interventions was not achieved; however, the score is close to 5, and the CI suggests that the level has been reached, which means that further investigation and changes will be required soon.Contrary to our findings, a study showed that computer workers who reported a lower job demand had pain less frequently in all anatomical areas investigated, except in the lower back; the Rapid Upper Limb Assessment (RULA) score in the workstation observational assessment differed significantly between the groups with and without pain.16 However, a systematic review conducted by Paksaihol et al.22 did not confirm that psychosocial factors have a predictive value for upper-extremity complaints.Another hypothesis about a lower job demand in individuals with pain is that they tend to be more cautious because of previous experiences of musculoskeletal disorders, which generate feedback influencing the perception of mental stress and job organization.15 In this study, the participants, despite having an acceptable level of education, were not experts in the topic.The correlation analysis included ROSA total scores and MUEQ workstation and body posture domain scores, as they are equivalent constructs; however, they did not correlate, probably because workers and observers had different perceptions. As previously mentioned, self-report tools may be poorly reliable because they are influenced by interpretation.28 showed a relationship between musculoskeletal symptoms and poor upper-extremity postures. In contrast, Gawke et al.29 analyzed physical aspects of the work environment together with psychosocial factors and found no associations with neck and upper-extremity complaints.Also, although workers were asked to maintain the postures they usually adopted during the assessment, these may have been modified, as the analysis of symptomatic and asymptomatic participants showed no statistical difference. Previous studies30 there is insufficient data in the scientific literature to confirm that computer work is associated with neck and upper-extremity complaints. A study conducted by Turci et al.27 to evaluate computer workers at a private institution suggested that symptoms may not be linked to the occupational activity.Regarding self-reported pain, the data suggest that it is not caused by the workstation or by occupational factors. Therefore, this supports the idea that factors not controlled for in this study may have contributed to the onset of pain, such as level of physical activity, sleep quality, diet, and other activities, either paid or unpaid, that employees may have engaged in outside the study setting. According to Mattioli et al.,A limitation of this study was the sample size; thus, additional studies with larger samples and similar studies addressing other private sector categories for wider data coverage should be conducted. Furthermore, psychosocial aspects such as pain catastrophizing, anxiety and depression, beliefs, fear, and pain avoidance were not controlled for. A strength of this study was the correlation analysis between the MUEQ tool, which shows self-perceptions of computer workers, and the ROSA checklist, which captures ergonomic and biomechanical characteristics of computer workers by observers. The results demonstrated that those viewpoints may be divergent.Asymptomatic individuals are subject to higher job demands probably because they have not previously experienced significant pain, although they have other complaints, such as stiffness, disability, weakness, edema, and paresthesia. Thus, absence of pain does not mean absence of complaints that could compromise occupational health. Symptomatic individuals, in turn, have greater trouble in aspects such as reduced amount of time spent on work and performance of work requiring extra effort. Regarding the findings of the observational assessment, workstation interventions are not required; however, this should be analyzed cautiously, given that further investigations are required, such as anthropometric measurements.


Eidolon helvum  and Rhinolophus sp. , followed by Hipposideros sp. . Frugivorous bats were predominantly infected with beta coronaviruses from the Nobecovirus subgenus (93.8%), in which at least 6 species/genus-specific subclades were observed. In contrast, insectivorous bats were infected with beta-coronaviruses from different subgenera (Nobecovirus (8.5%), Hibecovirus (32.8%), Merbecovirus (0.5%) and Sarbecovirus (57.6%)) and with a high diversity of alpha-coronaviruses. Overall, our study shows a high prevalence and genetic diversity of coronaviruses in bats and illustrates that Rhinolophus bats in Africa are infected at high levels with the Sarbecovirus subgenus, to which SARS-CoV-2 belongs. It is important to characterize in more detail the different coronavirus lineages from bats for their potential to infect human cells, their evolution and to study frequency and modes of contact between humans and bats in Africa.Bats are at the origin of human coronaviruses, either directly or via an intermediate host. We tested swabs from 4597 bats (897 from the Democratic Republic of Congo (DRC), 2191 from Cameroon and 1509 from Guinea) with a broadly reactive PCR in the RdRp region. Coronaviruses were detected in 903 (19.6%) bats and in all species, with more than 25 individuals tested. The highest prevalence was observed in  Rhinolophus bats in Asia, and a recent study suggests at least two zoonotic events with one lineage that became predominant . Mo. MoRhinoEidolon helvum bats from Guinea, Cameroon and DRC were infected with the same Nobecovirus subclade, but a small minority (3/236 sequences) fell in the subclade dominated by Epomophorus and Micropteropus species. On the other hand, Rhinolophus bats were infected with a wide diversity of alpha- and beta-CoVs; i.e., at least 3 different subgenera of alpha-CoVs and 3 subgenera of beta-CoVs, including 3 Nobecovirus subclades . This was not homogenous among species; for example, equal proportions of positivity were seen for Epomophorus sp. and Rousettus aegyptiacus bats, and a higher prevalence was seen in male bats for Epomops sp. and Eidolon helvum  (p = 0.57), but the results differed according to species and genus, as shown in We compared whether age or sex could play a role in coronavirus positivity using PCR. Overall, among all bat samples tested, 18.0%  of female and 20.9%  of male bats were positive for coronaviral RNA . For fru 0.0197) . In insep < 0.0001) (p < 0.0001) and for the majority of species for which sufficient samples from both age categories were tested, i.e., Eidolon helvum , R. aegyptiacus  and Rhinolophus sp. , except for Epomophorus bats, but the number of juvenile bats tested for this species was low. For insectivorous bats, equal detection rates were observed for juvenile and adult bats, but overall, a low number of juvenile bats was tested. In Cameroon, age determination of bats differentiated between adults and subadults. Eidolon helvum, Rousettus aegyptiacus and Rhinolophus sp.Prevalence was higher in juvenile bats; i.e., 34% (29.3–38.7%) versus 18.7% (17.5–19.9%) in adult bats  . This trp = 0.09), but the detection rate of coronaviruses was lower in lactating females (11.8% (4.9–18.6%)) than in non-lactating bats (22.7% (18.6–26.7%))   .Epomophorus species in DRC or Hypsignatus monstrosus, Mops and Rhinolophus species in Cameroon [Eidolon helvum but also in Rhinolophus bats, for which high numbers have been tested. We also identified a wide diversity of coronaviruses, with representatives of almost all known subgenera of alpha- and beta-CoVs and identified a subset of strains that cannot be classified in the alpha-CoV genus. We detected bat CoVs (n = 199) that belong to 3 subgenera that also harbor HCoV strains known to be pathogenic for humans, i.e., Sarbecoviruses, Merbecoviruses and Duvinacoviruses. This is also the first study that shows that Sarbecoviruses are widely present in Rhinolophus bats in Africa, representing 114 of the 275 sequences (41.4%) retrieved from the 306 positive Rhinolophus bats that have been detected in this bat genus in our study.We conducted a large survey to study the prevalence and genetic diversity of coronaviruses in almost 4600 bats from West and West Central Africa and provide significant new information on coronaviruses in bats from Guinea, West Africa and on species that were under-sampled in previous surveys in Cameroon and DRC, such as Cameroon ,41. OverHypsignathus monstrosus are infected with Nobecoviruses, and mainly with the Eidolon helvum-specific clade, most likely because they roost in the same fruit trees, as is the case in Yaoundé, Cameroon, where the majority of them have been sampled and where a large colony of Eidolon helvum bats is present. Representatives of the Hibecovirus subgenus have been identified mainly in Hipposideros bats but also in a significant proportion of Rhinolophus bats in Cameroon, especially in those that share habitats in a cave located in the southwest, thus confirming host switching of coronaviruses among bat species that share habitats, as previously reported [As previously reported, we observed host specificity at the genus and/or species levels . Nobecovreported .Rhinolophus bats in Asia and Europe and phylogeographic clustering has been reported in Asian Rhinolophus bats, which have been largely studied because Chinese Rhinolophidae are the natural reservoir for Sarbecoviruses [Rhinolophus bats and pangolins from Asia fall into lineage 5 [Rhinolophus bats from Cameroon and Guinea fall into lineage 4 but form separate clusters with the other Sarbecoviruses identified in Rhinolophus bats from East Africa , thus illustrating phylogeographic clustering of African Sarbecoviruses. Nevertheless, Sarbecoviruses from Asian lineages 1 and 5 co-circulate in the same geographic area and are at the origin of SARS-CoV-1 and 2, respectively. This highlights that more sampling has to be done in Rhinolophidae in Asia, but also in Africa to examine further genetic diversity, geographic clustering and co-circulation of Sarbecovirus lineages. More studies are also needed to confirm whether all African strains are unable to utilize human ACE2 and are not able to infect human cells, as shown by in vitro studies [Rhinolophus bats infected at high rates (34%) with Sarbecoviruses has been identified in Cameroon in a cave that is frequently used by hunters as shelter for protection during bad weather conditions (rain) and where Rousettus aegyptiacus bats are hunted during the whole year for consumption , which implies thus that humans might be in contact with guano (bat feces) dropped on the cave’s floor or with air saturated with contaminated aerosols. Our exploratory study on knowledge, attitudes and practices in Southern Cameroon showed that surrounding villages did not exploit bat guano as fertilizer [Sarbecoviruses are widespread in oviruses ,43,44. Fineage 5 ,48,49,50 studies . Howeverrtilizer , in contrtilizer .Rhinolophus bats and Duvinacoviruses in Hipposideros bats. Nevertheless, Rhinolophus, Hipposideros and Rousettus aegyptiacus bats are infected with at least 3 to 6 different subgenera of alpha- and beta-CoVs, illustrating host switching most likely because they roost together in the same caves. Among the frugivorous bats, only R. aegyptiacus is infected to some extent with alphacoronaviruses, representing around 20% of the infections in this species. The majority belong to the Decacovirus subgenus, which includes the HKU10 strain identified in a Rousettus bat from China [Additionally, for alpha-CoVs, species-specific clades are seen; for example, Rhinacovirus and a separate clade of unclassified viruses were predominantly observed in om China .We also confirmed that juvenile and subadult bats are infected at higher rates than adult bats, as previously reported ,53. ThisEidolon helvum, which are one of the most common bats in Africa and roost in fruit trees in gardens of houses in cities and villages. For MERS-CoV, it is clear that multiple spill-over events occurred, but with limited subsequent spread in humans [It is clear that humans are exposed to a wide diversity of bat coronaviruses in Africa, either directly through hunting and consumption or indirectly via contact with feces, urine or saliva on fruit or via guano. It will be important to evaluate to what extent some of these viruses can cross the species barrier or already cross the species barrier and lead to mild or asymptomatic infections. Serological assays with antigens from the different subgenera of alpha- and beta-CoVs need to be developed to evaluate this. Pre-existing immunity to other coronaviruses can also be one of the explanations for the lower morbidity of SARS-CoV-2 infections in Africa. This could be the case for coronaviruses that circulate at high rates in n humans . Althougn humans ,58, moleRhinolophus colonies are highly infected with Sarbecoviruses and it can thus not completely be excluded that a spillover event could occur and lead to another SARS-CoV variant in humans. More cross-sectional and longitudinal studies are needed to document the extent of Sarbecovirus infections in Rhinolophus colonies in Africa to identify periods and environments in which spillover to humans is at higher risk. More studies on human behavior and diversity of interactions with bats are also needed in addition to viral characterization, as well as the development of specific antibody assays to evaluate past spillover events or to evaluate risk for future events. Finally, our study used only a small fragment in the RdRp region, which has been shown to be coherent with the classification of whole genome sequences for the large majority of strains, as shown by Wilkinson and colleagues [Overall, we documented the high prevalence and genetic diversity of coronaviruses in different bat species from West and West Central Africa, especially in juveniles and subadults. More studies are needed to identify the high-risk periods, i.e., presence of high proportions of juvenile and subadult bats, to evaluate risk for spillover events for the different bat species. Importantly, our study shows that certain lleagues . Neverthlleagues ,59. Ther


Acute ischemic stroke has a high incidence in the plateau of China. It has unique characteristics compared to the plains, and the specific relationship with altitude has not yet been appreciated. This study aimed to investigate the specificity of the plateau's anterior circulation acute ischemic stroke in China.To retrospectively collect clinical data of patients with first-episode acute ischemic stroke in the anterior circulation in Tianjin and Xining city. The differences in clinical presentation, laboratory, and imaging examinations were compared.P = 0.010) and had a history of dyslipidemia, higher levels of inflammatory markers, erythrocytosis, and alcohol abuse. The main manifestations were higher diastolic blood pressure , triglycerides , CRP , homocysteine levels ; larger infarct volume  and worse prognosis. Patients at high altitudes had higher atherosclerotic indexes in cIMT and plaque than those in plains.Patients at high altitudes showed a significant trend toward lower age (61.0 ± 10.2 vs. 64.8 ± 8.1, The natural habituation and genetic adaptation of people to the particular geo-climatic environment of the plateau have resulted in significant differences in disease characteristics. Patients with the anterior circulation acute ischemic stroke in the plateau show more unfavorable clinical manifestations and prognosis. This study provides a preliminary interpretation of the effects of altitude and suggests developing preventive and therapeutic protocol measures that are more appropriate for the plateau of China. Stroke has a high rate of death and disability and is the second leading cause of death worldwide after coronary heart disease . Stroke The epidemiological distribution of ischemic stroke in China is distinctly geographical, with a high incidence in the plateau areas of northwestern China, such as Tibet and Qinghai , 5. An aIn this study, we compared the clinical manifestations, imaging data, and prognosis of patients with anterior circulation acute ischemic stroke (AIS) in the highland and plain regions through a retrospective method to investigate the specificity and provide informative comments on the prevention and treatment of the disease.Patients with anterior circulation AIS are from Tianjin Huanhu Hospital and Xining Third People's Hospital. Both hospitals are provincial-level stroke treatment centers with similar pre-hospital transport, diagnosis, treatment, and care of patients.Tianjin city is located in the North China Plain in eastern China, with a geographical location of 117°10′E, 38°34′N. The average altitude is 3.5 m, the average annual atmospheric pressure is 100.4 kpa. Xining city is located on the Tibetan Plateau in northwestern China, with a geographical location of 101°77′E, 36°62′N. The average altitude is 2,275 m, the average annual atmospheric pressure is 77.3 kpa. The ethnic groups in both places are mainly Han Chinese.We retrospectively selected a total of 379 patients diagnosed with first-episode anterior circulation AIS with a pre-onset mRS score of 0–1, >18 years of age and permanent residents (>10 years of residence) from May 2020 to 2021 in both regions electronic medical record systems. The diagnosis of AIS is based on the WHO definition, meeting clinical symptoms and examination criteria, and confirmed by computed tomography or magnetic resonance imaging of the brain. Exclusion criteria included: non-first episode, non-local patients; not caused by vascular diseases such as a tumor, trauma, hematologic disorders; previous use of drugs such as aspirin and statins; previous history of old cerebral hemorrhage/ischemia; transient ischemic attack (TIA), time from onset to hospital admission more than 3 days, and patients who were lost followed up for 90 days after discharge . A total of 181 patients were finally included in the study after screening with detailed and complete basic information, imaging examinations, and relevant laboratory test data .Data collected included basic information on admission, vital signs , imaging examinations (MRI/CT/Carotid ultrasonography), routine blood and biochemical tests, coagulation, medical history , medication history , National Institute of Health stroke scale (NHISS score). All data were selected from patients' first examination results within 24 h of admission. The follow-up endpoint was defined as day 90 after hospital discharge, and the day 90 mRS score was recorded as a prognostic indicator (dead within 90 days of follow-up were recorded as 6 points).History of hypertension, coronary artery disease, and diabetes mellitus was based on previous and discharge diagnoses. Dyslipidemia was diagnosed based on past medical history and discharge diagnosis, with TC ≥ 6.2 mmol/L, TG ≥ 2.3 mmol/L, LDL-C ≥ 4.1 mmol/L, HDL-C ≤ 1.0 mmol/L meeting any of the diagnostic criteria , 10. Eryhttp://www.itksnap.org) (Head MRI images were processed using ITK-SNAP software (nap.org) . We usednap.org) .t-test, the categorical variables were analyzed by Chi-square test and Fisher exact test. Non-normally distributed and non-parametric data using the Mann-Whitney U test and rank sum test. P < 0.05 was considered indicative of a statistically significant difference.All participants were classified into two groups according to altitude levels. Continuous variables were presented as mean ± SD or median (interquartile range). Categorical variables are expressed as frequency (percentage). SPSS v25.0 statistical software (IBM Corp.) was used for the data analysis. The continuous variables were analyzed by Student's One hundred and eighty one patients with anterior circulation AIS were included in this study: 133 from Tianjin and 48 from Xining. The basic characteristics and vital signs of the patients as shown in P = 0.010).Patients in both regions were predominantly Han Chinese and male in terms of ethnicity and gender distribution. Patients at high altitudes had significantly higher respiratory rate and heart rate, while oxygen saturation was significantly lower, and there was no difference in body temperature between the two regions. In terms of age of onset, patients at high altitudes showed a significant trend toward a lower age  mmol/L vs. 1.3 (0.9) mmol/L, P < 0.001]. HB/RBC levels were significantly higher in routine blood tests, and PLT levels were lower than in the plain; prolonged APTT and PT were demonstrated in coagulation function. In the vascular inflammatory indexes, homocysteine  and the blood C reactive protein (CRP) levels  were significantly higher in patients at high altitudes. Moreover, in carotid ultrasonography, the CCA-IMT  and the maximum thickness of plaque  were significantly higher in patients from high-altitude areas .We used the mRS score of 0–2 as the evaluation index of good prognosis, and it was seen that the proportion of patients with good prognosis was significantly higher at low altitude than at high altitude  in the air also decreases. Oxygen is inhaled from the respiratory tract and passes through the alveoli, arterial blood, and cellular mitochondria. During the whole transportation process, the oxygen transfer volume decreases in a “waterfall” style due to the step-by-step decrease of PaO2, which eventually leads to oxygen availability in the intracellular mitochondria . Lee's study found that ten h of daily cold exposure at 19°C room temperature increased human insulin sensitivity, glucose uptake, and metabolic rate after 1 month . Genome-Long-term chronic hypoxia stimulates the enhancement of bone marrow hematopoiesis and promotes the production of red blood cells and Hb to increase the oxygen-carrying capacity of blood and tissue oxygen supply. Therefore, among the pathological components of the thrombus, red thrombi with a predominant proportion of RBC and HB may be more frequent, suggesting that anticoagulation may be more effective. Therefore, in the treatment of AIS, it is essential to address the issues in the selection of antithrombotic drugs and the need to adjust the therapeutic dose in highland areas.Carotid artery intima-media thickness (cIMT) and carotid plaque measures are commonly used to assess atherosclerosis , 13. We The hypoxic environment in the highlands induces high expression of the HIF pathway, and HIF-1α can promote the secretion of large amounts of inflammatory-related factors (such as IL-6/VEGF/IL-1β) from lipids, contributing to endothelial damage and aggravating the systemic and intravascular inflammatory response –38. ThusDue to the limitations of this article, most of the clinical information does not guarantee the accuracy of retrospective scoring, and we could not provide accurate TOAST sub-type retrospectively. We attempted to analyze further the pathogenesis based on the results of the article: The presence of larger infarcts usually excludes the small artery occlusion (SAO). Instead, it may suggest a cardioembolic stroke . The lowThe use of statins facilitates lipid depletion in atherosclerosis and reduces inflammatory cell adhesion and monocyte recruitment by endothelial cells . The posComparison of infarct volumes and NHISS scores for the anterior circulation AIS between the two regions revealed that the plateau region had larger infarct volumes and more severe symptoms of neurological impairment, highlighted by impaired consciousness. There was significant altitudinal variability in infarct volume and degree of neurological impairment, the same as the currently available studies . All patFurther grouping of NHISS scores revealed that plateau patients exhibiting mild, moderate, and moderate-severe AIS infarct volumes were significantly larger than those in the plains. In other words, the plateau population has improved the degree of tolerance of nerve cells and the body to hypoxia during the long-term habituation and genetic adaptation to the hypoxic environment. However, once AIS occurs, people in plateau areas need larger infarct volumes to get to the same clinical symptoms as plain patients, reflecting the decreased sensitivity of plateau people to AIS. The human body's sensitivity to the disease is a mechanism to avoid further damage, which is not conducive to the early detection and treatment of plateau AIS.Moreover, homocysteine, a sulfur-containing amino acid formed during methionine metabolism, is an independent and graded predictor of cardiovascular and cerebrovascular events . The main mechanisms by which increased homocysteine leads to vascular events include impairment of vascular endothelial function, increased oxidative stress, abnormalities in lipid metabolism, and induction of thrombosis . FurtherTreatment with folic acid, vitamin B6, and B12 effectively lowers plasma homocysteine levels, and there is an optimistic view that lowering homocysteine levels can improve the prognosis of AIS , 49, 50.The plateau is one of the most challenging environments for human beings due to its extreme geographic climate, most notably to face the problem of hypoxia. According to Darwin's evolutionary mechanism, under the pressure of environmental and natural selection, humans and other life forms have changed their characteristics over a period. A short period of compensatory adjustment of function and structure is called acclimatization. Genetic adaptation is profoundly modified and reconstructed through genetic mutation, then consolidated through reproduction to future generations , 52.2 was between 2.5 and 3.5 kPa, equivalent to a hypoxic environment at 7,500 m above sea level. Thus, the environment in which the human fetus develops was described by him as the “Everest in utero” , which induces acute high altitude pulmonary edema (HAPA) and pulmonary hypertension . Ahsan eAt present, in the field of plateau genomics, we have started to explore the long-standing problems in plateau and evolutionary biology. From the research content, the mechanism of plateau adaptation is altered by multiple molecular pathways to genetic factors. The specific gene regulation mechanisms of plateau adaptation are still unclear, and there is almost a gap in research related to plateau encephalopathy. Functional studies of genetic loci associated with genetic adaptation to the plateau are of great importance in the prevention and treatment of acute and chronic diseases of the plateau.In the anterior circulation AIS, patients in the highlands exhibited lower age, larger infarct volumes, more severe neurological symptoms, and poorer prognosis than the plains. The significant inflammatory response and atherosclerotic factors are essential for anti-inflammatory, lipid-lowering therapy in highland areas. We suggest that improving the dietary structure, reducing the high-fat diet, increasing the intake of folic acid and vitamins, limiting alcohol, strengthening the monitoring and management of blood pressure, blood lipids, and inflammatory indexes, and enhancing the awareness of health care have essential positive effects on the prevention of acute ischemic stroke in high altitude areas.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Tianjin University Huanhu Hospital. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.YY, and XZ: study concept and design. YY, JL, and WF: data acquisition. YY, XZ, and HR: statistical analysis. HR, XA, and YH: interpretation of data. YY: manuscript drafting. JL and YH: review and editing. YH: supervision. All authors contributed to the article and approved the submitted version.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.


Retinitis pigmentosa (RP) is the most common retinal hereditary dystrophy, which can lead to blindness if it progresses. Similarly, open-angle glaucoma (OAG) is a genetic disorder. The similarities in genetic variants and pathophysiology between RP and OAG have been reported. We sought to explore whether patients with RP have a significantly higher risk of OAG development.  We enrolled patients with RP into the RP group through Taiwan's National Health Insurance Research Database from 2001 to 2013; we included a comparison group of 1 : 4 age- and gender-matched individuals without RP. We performed a Cox regression analysis to estimate the crude and adjusted hazard ratios (HRs) for OAG. We adjusted the following confounders in the Cox regression model: age, gender, diabetes mellitus, hypertension, and chronic kidney disease. p < 0.0001). On univariate Cox regression analysis, the hazard of OAG development was significantly greater in the RP group than in the comparison group with an unadjusted HR of 2.86 . The increased risk persisted after adjusting for confounders .  We enrolled 6,223 subjects with RP and 24,892 subjects for comparison. The mean age of the cohort was 49.0 ± 18.1 years. The RP group had significantly higher percentages of diabetes mellitus, hypertension, and hyperlipidaemia. The cumulative incidence of OAG in patients with RP was 1.57%; this was significantly higher than that in the comparison group (0.58%,  This nationwide population-based cohort study showed that people with RP are at a significantly greater risk of developing OAG than individuals without it. Retinitis pigmentosa (RP) is a genetic disorder involving the breakdown and loss of photoreceptor cells . PatientGreenstein et al. reported that RP and OAG had similar pathways in cone vulnerability, including S and M cone losses . BesidesHowever, very few studies have investigated the relationship between RP and OAG , 12. A cThe National Health Insurance (NHI) program of Taiwan covers the healthcare services of 99.82% of residents . The NHIRD maintained by the National Health Research Institutes of Taiwan is released for research purposes and contains demographic data for all NHI enrollees and health care, medical prescription, and surgical management data for ambulatory and in-hospital patients in Taiwan. Diagnoses are registered according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. We used NHIRD data on health care claims for the entire population from 1996 to 2013 for this retrospective cohort study. To ensure confidentiality, the National Health Research Institutes (NHRI) encrypted the personal information of all patients in the database prior to releasing data for academic use. Written informed consent was waived according to the rules of the Institutional Review Board. This study was approved by the Ethical Committee of National Yang-Ming University Hospital. (no. 2015A018).We selected patients diagnosed of RP (ICD-9-CM code 362.74) from the NHIRD from January 1, 1996, to December 31, 2013. RP was confirmed by ophthalmologists through a well-acknowledged standard diagnostic protocol with retinal bone-spiculae pigments, arteriolar attenuation, and waxy pallor of the optic disk under indirect ophthalmoscopy . Visual Thereafter, we randomly selected individuals who had never been diagnosed of RP as a comparison group at a ratio of 1 : 4 and matched them with the RP group in terms of age, gender, and index year (year of enrolment). All eligible RP subjects and comparisons had never been diagnosed with OAG before the index date.We compared whether the two groups developed subsequent OAG (ICD-9-CM code 365.1) confirmed by ophthalmologists by following up to the end of 2013. Patients diagnosed with OAG should have a glaucomatous visual field defect or glaucomatous optic neuropathy with an open angle . AlthougWe identified comorbidities, which confound the association between RP and OAG  as covart-test for continuous variables and the chi-squared for categorical variables.After investigating the demographic/clinical characteristics of RP and the comparison cohorts, we computed the group difference using the two-sample We used the Cox proportional hazard model to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the occurrence of OAG according to each variable in the univariate and multivariate analyses. Covariates adjusted in the regression analysis were age, gender, diabetes mellitus (DM), hypertension (HTN), hyperlipidaemia, and chronic kidney disease. To avoid immortal time bias, we considered comorbidities as time-dependent variables.p value < 0.05 was considered statistically significant.All analyses were performed using SAS version 9.3 . A In this study, we enrolled 6,223 subjects in the RP group and 24,892 matched comparisons. p < 0.0001), HTN , and hyperlipidaemia . However, the prevalence of chronic kidney disease between the two groups was similar . During the study period, the cumulative incidence of OAG was 1.57%, which was significantly higher than that of the controls (0.58%) (p < 0.0001).Compared to the comparison group, the RP cohort had significantly higher percentages of patients with DM .RP was still significantly associated with an increased risk of developing OAG  after adjustment for covariates. In addition, age was a significant risk factor for RP on univariate and multivariate analyses. The adjusted HR for patients over 60 years was 2.45 relative to those younger than 40 years . However, after adjusting the covariates, neither gender nor comorbidities remained a significant risk factor for OAG.This 13-year population-based study from the Taiwan NHIRD showed a significantly higher cumulative incidence of OAG in the RP group compared to age- and gender-matched controls. After adjustment for age, gender, and comorbidities in a multivariate Cox regression analysis, RP still had a significantly greater risk of incident OAG.The worldwide prevalence of RP varies from 0.014% to 0.04% . RP is rConcerning the age of onset for RP, several studies have shown its variation with ethnicity and genes . AccordiAccording to a large cohort study in China, the prevalence of glaucoma in patients with RP was 1.6% . In our First, the S and M cone losses in patients with RP and OAG were similar, which could be due to hypoxia . HypoxiaSecond, both RP and OAG have similar gene mutations . HeterozOur study is the first to investigate the association between RP and OAG on a population-based scale. One of our strengths is that we had accurate information owing to the comprehensiveness and completeness of NHIRD, in which demographic data, diagnoses, examinations, and therapies are recorded and confirmed. The National Health Administration routinely checks medical charts to ensure that patients have correct diagnoses. Besides, we enrolled patients from the NHIRD from January 1, 2001, to December 31, 2013, which was the longest study period known. Furthermore, our study not only investigated the association between RP and OAG but also adjusted the impacts of the confounders. Therefore, the significant association between RP and OAG in our study was likely a real phenomenon.One limitation of our study is that the clinical diagnosis of some cases of RP, especially RP variants, may be missed. Fortunately, we have used a series of thorough examinations such as fundus ophthalmoscopy, visual field, electroretinogram, and optical coherence tomography to increase the accuracy of the diagnosis. Another limitation of our study is the lack of genetic sequencing or laboratory data. Further studies will be needed to combine the Taiwan Biobank with the NHIRD to elucidate whether specific genes or biochemical profiles may explain the relationship between RP and OAG.Our study concluded that people with RP have an increased risk of developing OAG. Therefore, ophthalmologists should be aware of the possible risk of developing OAG in patients with RP and pay more attention to the changes in the optic nerve during the regular follow-up.


Objective: Meta analysis was used to explore the efficacy and safety of Sintilimab in the treatment of cancer.Methods: The databases of CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, the Cochrane Library and EMBASE were searched by computer to collect the randomized controlled trials published as of March 2022. The retrieval work was completed by two researchers alone. They screened the literature and extracted the data according to the nanodischarge standard, using Revman 5.4 software. The included studies were statistically analyzed.Results: Six RCTs were included in this study, including 1,048 cases of Sintilimab and 711 cases of other anticancer drugs. Compared with the control group, the overall survival  and progression free survival  of cancer treated with Sintilimab were longer and more effective. Moreover, the risk ratio of any grade of adverse reactions  and above grade III adverse reactions  in the treatment of cancer with Sintilimab was lower and the safety was better.Conclusion: Compared with non-Sintilimab group, Sintilimab treatment can improve the clinical efficacy of tumor patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for cancer patients. Systematic Review Registration: (website), identifier (registration number).The global epidemiological survey shows that cancer has high incidence rate and mortality rate. Clinically, traditional dual drug chemotherapy including platinum, paclitaxel and adriamycin has always been the standard first-line therapy for cancer patients . In receWe searched CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, the Cochrane Library, EMBASE and other databases by computer. In addition, we also searched the references and meeting minutes included in the study to supplement and obtain relevant materials. Chinese key words: Sintilimab, cancer, randomized controlled trial English key words: Sintilimab, IBI308, IBI-308, cancer, randomized controlled trials, RCTs. The search time is up to March 2022.Inclusion criteria: ① the type of study is RCTs; ② The subjects were patients diagnosed with cancer by clinicopathological examination; ③ Intervention measures: patients in the experimental group were treated with Sintilimab, and patients in the control group were treated with non Sintilimab (the treatment without Sintilimab); ④ The primary outcome measures were overall survival (OS) and progression free survival (PFS). The secondary outcome measures were adverse reactions at any level and adverse reactions above grade 3.Exclusion criteria: ① repeatedly published literature; ② Documents that cannot obtain original data or contact the author to obtain the original text; ③ Abstract, review, meta-analysis, case report and animal experiment; ④ Non Chinese and English literature.The Newcastle Ottawa scale (NOS) was used to evaluate the quality of the included study , accordiTwo researchers independently screened the literature, extracted the data and cross checked. In case of any difference, it shall be settled through discussion or negotiation with a third party. During literature screening, first read the title. After excluding the obviously irrelevant literature, further read the abstract and full text to determine whether to be included. If necessary, contact the original study author by email or telephone to obtain information that is not determined but very important to this study. Data extraction contents include: ① basic information of the included study: first author, year of publication, sample size, outcome indicators and outcome measurement data.p < 0.05). I2 is used to evaluate the heterogeneity. If the heterogeneity test result I2 is less than 50%, it means that there is no statistical heterogeneity among the research results, and the fixed effect model is used; If the heterogeneity test result I2 > 50%, analyze the source of heterogeneity. If the heterogeneity still exists, select the random effect model to estimate the combined effect.Data were processed through Revman5.4 software. Relative risk ratios (RR) and 95% confidence interval (95% CI) were used as effect indexes for counting data, and the difference was statistically significant  and three conference papers by computer, and selected 17 according to the title and abstract. After full-text analysis and evaluation, we excluded 11 literatures with abnormal data, incomplete information or unavailable due to non comparative research, and finally included 6  literatu2 = 0%, p = 0.74. There is no statistical heterogeneity among the studies. The fixed effect model is used for analysis. The results showed that HR = 1.64 , suggesting that Sintilimab can significantly improve the OS of cancer patients, as shown in Comparison of OS: four studies can obtain the OS data of cancer patients treated with Sintilimab. For heterogeneity analysis, I2 = 0%, p = 0.90. There is no statistical heterogeneity among the studies. The fixed effect model is used for analysis. The results showed that HR = 1.89 , suggesting that Sintilimab can significantly prolong PFS in cancer patients, as shown in Comparison of PFS: the PFS data of cancer patients treated with Sintilimab can be obtained from four studies. For heterogeneity analysis, I2 = 77%, p < 0.00001. There is statistical heterogeneity among studies, which is analyzed by random effect model. The results showed that HR = 0.87 , suggesting that the incidence of any level of adverse reactions in patients with Sintilimab was low, but there was no significant difference in the results, as shown in Comparison of adverse reactions at any level: Six studies can obtain the data of any level of adverse reactions  of cancer patients treated with Sintilimab. For heterogeneity analysis, I2 = 18%, p = 0.26. There is no statistical heterogeneity among the studies. The fixed effect model is used for analysis. The results showed that HR = 0.84 , suggesting that the incidence of grade III and above adverse reactions in patients with Sintilimab was low, but there was no significant difference in the results, as shown in Comparison of adverse reactions above grade III: Six studies can obtain the data of more than grade III adverse reactions  of cancer patients treated with Sintilimab. The heterogeneity analysis is carried out, with IThe publication bias assessment of this study was performed only in OS and PFS. The funnel plot is symmetrical, indicating no significant publication bias . SensitiSintilimab is a monoclonal antibody against programmed cell death protein 1. It can block the interaction between PD-1 and its ligand and help T cells restore their anti-tumor effect. In 2018, Sintilimab has been approved by the State Administration of medicine of China for the treatment of patients with recurrent or refractory classical Hodgkin’s lymphoma. In recent years, a large number of studies have reported the anti-tumor effect of Sindilimab. In general, Sintilimab has similar anti-tumor effect and better safety compared with other ICIs (such as Nivolumab and Pembrolizumab) in Hodgkin’s lymphoma, natural killer T-cell lymphoma and advanced non-small cell lung cancer .p < 0.001) and PFS  compared with chemotherapy alone. Martin Reck et al. . The incidence of grade 3–5 treatment-related adverse events in the Sintilimab group was lower than that in the chemotherapy group .In phase three clinical trials, the combination of ICIs and chemotherapy is rapidly developing into a first-line treatment for many cancers. Paz-Ares et al.  showed tk et al.  found thk et al.  evaluateIn this meta-analysis, we evaluated the efficacy of Sintilimab in cancer patients and selected OS and PFS as the primary outcomes. The results showed that in terms of effectiveness, Sintilimab improved the HR of OS and PFS, indicating that patients receiving immunotherapy had better OS and PFS than patients receiving ordinary chemotherapy. In terms of safety, the risk ratio of adverse reactions at any level and above in the Sintilimab treatment group is lower than that in the control group. Although there is no significant difference in the results, it also suggests that the safety of Sintilimab treatment is higher than that of ordinary chemotherapy drugs, and it is not easy to produce more common typical adverse reactions . According to the above results suggest that in the process of clinical practice, especially for non-small cell lung cancer, liver cancer, non-hodgkin’s lymphoma, such as cancer patients during chemotherapy, Sintilimab can be used as the preferred drug resistance. It can not only bring a higher response rate, also can prolong the overall survival and disease progression, and caused most of the adverse reaction of one to two levels. With a long-lasting therapeutic response and tolerable toxicity, Sintilimab has shown promising efficacy overall.It has to be said that this study also has some limitations: ① after systematic retrieval and screening, only six limited literatures were included for systematic evaluation and meta-analysis, resulting in a small sample size; ② The heterogeneity of individual statistical results may affect the credibility of the research results; ③ Different cancer types in different studies may increase heterogeneity and affect the reliability of results. However, in the study, in order to better reduce the above bias, when implementing retrieval and data consolidation, this study should be scientifically and objectively reported according to the Newcastle Ottawa scale as much as possible.In conclusion, compared with non-Sintilimab group, Sintilimab can prolong the OS and PFS of patients in the treatment of cancer, with better clinical efficacy and high safety. Sintilimab may be a promising treatment for cancer patients.