Influenza is a global serious public health threat. Seasonal influenza among children in Chongqing has been a heavy health burden. To date, few studies have examined the spatial and temporal characteristics of influenza. This research sheds new light on correlating them with influenza outbreaks with data of over 5 years (2014–2018). All cluster outbreaks among preschool and school-age children reported in Chongqing were collected through the Public Health Emergency Management Information System. The demographical, epidemiological, and clinical data of the cases were analyzed. From 2014 to 2018, a total of 111 preschool- and school-based influenza-like illness outbreaks involving 3,549 cases were identified. Several clinical symptoms that were analyzed in this study showed significant contrast between influenza A and B. Spatial autocorrelation analysis over the 5-year data detected Xiushan district being the most likely cluster. The exploration of the spatial distribution and clinical characteristics of influenza cluster of children in Chongqing could help the effective implementation of health policies. Future studies should be conducted to monitor the outbreaks of influenza among children. Influenza is a globally prevalent disease. It is a leading cause of annual epidemics, especially in tropical and subtropical areas. Influenza viruses that can infect humans are divided into three types (A–C), while seasonal epidemics are generally caused by types A and B. Influenza A viruses have several subtypes on the account of antigenic shift, while influenza B viruses currently have only two genetically distinct lineages (B/Yamagata and B/Victoria) . Though Chongqing is the largest subtropical municipality located in Southeast China. Influenza poses a significant public health threat to Chongqing due to the humid subtropical monsoon climate and dense population. An annual average of 10,025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths . Few litVaccination is considered the best preventive measure against influenza –16, and Influenza is marked by sudden onset of fever, myalgia, headache, malaise, dry cough, sore throat, and nasal congestion –24. InflAn influenza-like case outbreak is defined as an unusually high number of influenza-like cases occurring within a short period of time in the same area or unit . In the 2. It has 26 districts, eight counties, and four autonomous counties  were developed by the Chinese National Ministry of Health to standardize the handling and management of influenza-like cases . The guiFor outbreaks of influenza-like cases that meet the reporting criteria, local agencies were required to collect samples of outbreak cases. Pharyngeal swabs, nasal swabs, and nasopharyngeal swabs of influenza-like cases within 3 days of onset were collected and placed into a sampling tube containing 3–4 mL sampling solution. The freshly collected specimens were transported to the influenza surveillance network laboratory within 48 h. After the samples of the outbreak were received, the influenza surveillance network laboratories were required to identify the influenza virus subtypes or lineages by means of nucleic acid test in 24 h. Real-time RT-PCR test was conducted for qualitative identification of influenza viruses in respiratory tract samples and virus-isolated cultures by using One-Step RT-PCR kit in accordance with the standardized protocols formulated by the National Technical Guidelines for Influenza Surveillance . The preThe number distribution of clustered cases is described by types and years to show the trend of influenza outbreaks in Chongqing. The demographic characteristics of patients with ILI were described, and the incidence was calculated by dividing the number of cases by the number of exposures. The number of exposures is defined as the number of a school or classroom depending on the specific condition of different schools. Pearson Chi-square test was conducted to test differences in independent association between categorical variables. Fisher's exact test was employed when sample sizes within cells were small (<5). The odds ratio (OR) and 95% confidence interval (CI) was also determined using the Pearson Chi-square test and used to evaluate the likelihood of contracting influenza in the regions.p-values (P < 0.05). The value of Moran's I is generally between −1 and 1. I > 0 indicates positive autocorrelation of the distribution, I = 0 indicates that the spatial distribution is random, and I < 0 means that the distribution has a global negative autocorrelation. The local indicators of spatial association (LISA) is composed of spatial autocorrelation present in the influenza incidence across an aerial dataset to each of the component areas. LISA map was used to cluster the significant spatial regions and display them in significant and clustering graphs . This study also utilized spatial autocorrelation analysis, with one district as a geographic unit. Global and local Moran's I were applied to identify the significant spatial autocorrelation regions of influenza in Chongqing . The glog graphs . When thg graphs , 32.From January 2014 to December 2018, a total of 111 preschool- and school-based ILI outbreaks were reported in Chongqing, China. A total of 3,549 cases of ILI were reported among preschool and school-aged children during the study period, with 3,403 laboratory confirmed cases, 145 virus-negative cases, and one fatal case. The general characteristics of all cases, including gender, incidence, region, and educational stage, are shown in A total of 1,846 male ILI cases included 1,776 laboratory-confirmed cases and 70 virus-negative cases, and 1,702 female ILI cases comprised 1,627 laboratory confirmed cases and 75 virus negative cases. The ratio of male to female was 1.09:1. Boys infected with influenza A (52.8%) and B (51.7%) were slightly more than girls, while the only death in 5 years was a female student in rural primary school.In terms of educational stage, students in special-needs school (15.82%) and those in kindergarten (9.57%) were the most affected groups. Regarding the subtypes and lineages of influenza virus, the incidence of B/Victoria (4.30%) and B/Yamagata (3.29%) was higher than that of other groups. Though 40.8% of children became infected in winter, the incidence rate of influenza in this season was the lowest (2.21%). The incidence rates of influenza A and influenza B were the highest in autumn (5.43%) and summer (5.81%), respectively. The incidence of influenza infection among children in rural areas (4.05%) was twice that in urban areas (1.90%).P < 0.0001) was determined to be a risk factor of influenza infection compared with living in urban areas.Living in rural areas  and dizziness (P = 0.002). Significant differences were found between the accompanying respiratory symptoms of influenza A and B, with cough (P < 0.001), nasal discharge (P < 0.001), and sore throat (P < 0.001) being more common in influenza B. Fisher's exact test showed that abdominal pain (P = 0.002) was significantly more frequent in patients with influenza B , the global spatial autocorrelation of influenza incidence in the 5 years was not significant. The results are shown in Influenza is one of the most prevalent diseases that poses a significant risk of severe or fatal outcomes, especially in preschool and school-aged children , 33–38. From 2014 to 2018, influenza A and influenza B alternately dominated the number of cluster outbreaks in schools in Chongqing. In 2017, when influenza B dominated, the number of cluster outbreaks reached its peak and declined in 2018. Similar to previous findings, influenza A viruses usually stay as the dominant viruses –43, whilIn this study, the general characteristics were compared, and the results showed that students in special needs school were at risk compared with kindergarten students. B/Victoria viruses and unidentified B lineage were found to be risk factors compared with H1N1, winter was a protective factor compared with spring, and living in rural areas was a risk factor of influenza infection.In line with prior results, younger children were more likely to become infected , 48, 49,B/Victoria virus also had a higher infection rate among preschool and school-aged students . In partHowever, several studies reported that the difference in influenza infection between rural and urban areas was not significant or even more cases in urban areas than in rural areas , 56. TheIn the analysis of clinical features of influenza A and B, the difference between the two groups were compared. Previous evidence supported that children with influenza B had greater adjusted odds of presenting with headache, sore throat, and abdominal pain. Cough, nasal discharge, and dizziness were also identified to be significantly more common in patients with influenza B , 57. TheThe seasonal distribution of influenza A and B showed a specific pattern of peaking in spring and winter according to the previous findings in Chongqing . Though The spatial distribution of influenza cases maps and spatial autocorrelation analysis confirmed the necessity of influenza intervention in Xiushan district. The complex geography, poor healthcare, and location in the southernmost part of Chongqing are responsible for the high incidence of epidemics in Xiushan. Moreover, Xiushan district, which is located in Southeast Chongqing, is an important channel connecting Chongqing to the southeast coastal economic circle. As a traffic stronghold, the population movement and increased contact made it easy to spread and invade Xiushan from Southeast China. Besides, schools in Xiushan are mostly boarding schools, and the closed environment may create conditions for the spread of influenza outbreaks. Thus far, the epidemic in Xiushan has not received sufficient attention, and no relevant studies have focused on the epidemic situation of influenza in this region. This study could enable the local government to pay increased attention to the influenza outbreaks among preschoolers and school-aged children in Xiushan. More proactive interventions, such as organizing vaccinations at the school level and school closures, should be taken in Xiushan.This study innovatively monitored influenza epidemic data in Chongqing City by spatiotemporal analysis and further explored the epidemic and spatial distribution characteristics of influenza, thus providing theoretical basis for the prevention and control of influenza in Chongqing. However, some areas of the study could still be improved, such as more data to provide a clearer trend analysis of the pattern of epidemic influenza. Besides, symptom data were collected within 3 days of diagnosis, and further data should be included given the effect of clinical treatments, such as drugs, and poor accuracy of reporting symptoms by young children. The data in this study were collected on cluster outbreak level, and the original data we collected were not case by case. Future research can consider collecting case by case data to allow for the application of more robust statistical methods. In addition, subsequent spatiotemporal analysis of preschool and school-aged children may consider including cases of sporadic influenza to improve the accuracy of the study. Finally, the reported findings are limited to Chongqing. Future studies should consider a national survey.In this study, the sociodemographic and clinical characteristics and temporal and spatial distribution of influenza A and B were explored, contributing to the differential diagnosis and school-based intervention of seasonal influenza A and B viruses. The results provide more information for health workers to control seasonal influenza epidemics among preschool and school-aged children in Chongqing.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.MY and XM: conceptualization. HZhu and XM: methodology and software. RO, MY, QZ, and HL: validation, visualization, and supervision. XM: formal analysis, writing–original draft preparation and writing–review and editing. HZha: investigation, resources, and data curation. MY: project administration and funding acquisition. All authors have read and agreed to the published version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


There is a gradual increase of female breast cancer under 35 years old, who was characterized as poor prognosis. Whether young patients could obtain greater survival benefits from breast-conserving surgery (BCS) than mastectomy remains controversial.Breast cancer patients (≤35 years old) were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into BCS and mastectomy group. Propensity score matching (PSM) was used to eliminate the distributional imbalance of variables among two groups. The influence of BCS on overall survival (OS) and breast cancer-specific survival (BCSS) was evaluated by Cox regression. Logistic regression was used to identify factors related to the benefit of BCS and to construct a nomogram. The nomogram was validated by the First Affiliated Hospital of Xi’an Jiaotong University cohort.P = 0.028) and BCSS (P = 0.042). A nomogram was established, and the AUC values both in the internal and external validation set were 0.780. The applicability of the model was verified in the PSM cohort and indicated that the survival advantage in the BCS-Benefit group was higher than that in the BCS-Nonbenefit and mastectomy group (P <0.001).Totally, 15,317 cases in the SEER database and 149 cases of external validation cohort were included. BCS was an independent protective factor for OS  that could identify appropriate candidates who benefit from BCS. The incidence of breast cancer in young women has been increasing since the mid-1990s and has become a leading cause of cancer death in them , while CThe option for local surgical treatment has a significant impact on the prognosis of breast cancer patients. The NSABP B-06 demonstrated that survival outcomes after breast-conserving surgery (BCS) combined with radiotherapy (BCT) were equivalent to those after mastectomy for those with early breast cancer . MoreoveThis study aimed to determine who benefits from BCS by extracting breast cancer patients under the age of 35 from the Surveillance, Epidemiology, and End Results (SEER) database for retrospective analysis. Logistic regression was used to screen out factors related to the benefit of BCS and constructed a nomogram. In addition, a cohort from the First Affiliated Hospital of Xi’an Jiaotong University was used for confirmation of the findings. Finally, suitable candidates for BCS were identified and referred for clinical treatment.We divided the samples into two groups according to the surgical approach: the BCS group and the mastectomy group. To adjust for unbalanced variable distributions between the two groups, we performed propensity score matching (PSM)  for age,P <0.05. A nomogram was then constructed based on the results to quantify the likelihood of a benefit from BCS in young patients and to screen possible candidates for receiving it. Next, we validated the predictive performance of the model on the validation set and external cohort. The discrimination and calibration of the model were evaluated by the time-dependent area under the receiver operating characteristic (ROC) curve (AUC) and calibration curve, respectively. Concurrently, we generated decision curve analysis (DCA) to assess the clinical utility of the model . A two-tailed We included 15,317 cases from the SEER database Table 1 P = 0.028) and BCSS . Moreover, other variables such as age, race, grade, T stage, N stage, and molecular subtype were also independent prognostic factors in young breast cancer patients. However, radiation and chemotherapy were not independent factors for OS and BCSS.The OS and BCSS before and after PSM of young breast cancer patients are shown in P = 0.002), marital status (P < 0.001), T stage (P < 0.001), N stage (P < 0.001), radiation (P < 0.001), and chemotherapy (P < 0.001) were screened out as independent influencing factors . Moreover, there was no significant difference in OS between the BCS-non-benefit group and mastectomy one (P =0.700). These results indicated that not all young breast cancer patients benefit from BCS, and some have an equal benefit to a mastectomy.Finally, we verified the use of the model in the PSM cohort. Based on the risk score in the nomogram, 1,259 patients were classified in the BCS-Benefit group, and 2,366 patients were classified in the BCS-Nonbenefit group. The KM survival curves were generated to observe the difference in survival benefits between groups Figure 8In recent years, the incidence of breast cancer in women under the age of 40 and even 30 has continued to increase, while the prognosis for them is poor. In addition, there are more challenges and demands in the treatment of young breast cancer patients, as well as more socioeconomic implications. There is a lack of reliable evidence for the treatment decisions due to the small proportion of young breast cancer patients in clinical trials , 24. TheSun et al. compared prognosis between BCT and mastectomy for early breast cancer in young patients under 40 years old, they found that there was no significant survival difference for 18-35 years old group . Quan etWe found that most young patients should receive BCS and benefit from it. This conclusion is consistent with the recommendations of many breast cancer conference guidelines. The St. Gallen Consensus Group in 2013 stated that young age is not an absolute contraindication to BCS . The EurOur analysis indicated that among patients under 35 years old, those who are older age, have lower T and N stage, radiation, as well as no chemotherapy, were associated with a benefit from BCS. Studies have shown that age is an independent risk factor for tumor recurrence after BCS . AccordiThe greater benefit of BCS without chemotherapy than with chemotherapy is seen in Logistic regression, and the following aspects should be considered. The cohort study in 127 hospitals in the UK (POSH) and the breast cancer study in young women in Europe (HOHO) showed that young breast cancer patients had a higher proportion of HR+ tumor compared with older women , 35. SimDespite our model having a promising predictive value in identifying appropriate candidates for BCS among young women with breast cancer, several limitations remain. First, some information is missing from the SEER database, such as BRCA1/2 mutation, Ki67, HER2 status before 2010, and tumor progression, which may affect the performance of the model. Second, the impact of systemic therapy on prognosis cannot be analyzed comprehensively, such as endocrine therapy, targeted therapy, and immune therapy. Third, PSM requires a large sample size to achieve high-quality matching, and may lose more data and cause the remaining samples to be unrepresentative. Finally, this is a retrospective study, which may have selection bias, and our findings need to be supplemented and validated with prospective studies.In conclusion, our findings suggest that BCS can bring better OS and BCSS than mastectomy for young breast cancer patients, but not all benefit from it. Herein we constructed a model for young breast cancer patients (≤35 years old) which could identify appropriate candidates who may benefit from BCS. For patients assigned to the BCS-Nonbenefit group, their OS did not differ from those who received a mastectomy. These findings could provide a reference for clinicians in therapy decisions.https://seer.cancer.gov/]. The original contributions presented in the study are included in the article/The dataset for this study can be found in the SEER database [SP: Conceptualization, Methodology, Validation. Writing - Original Draft. SS, HC: Formal analysis, Investigation. CZ, HZ: Software, Visualization. KW: Data Curation, Resources. JH: Writing- Reviewing and Editing, Supervision. JZ: Conceptualization, Writing - Review and Editing. All authors read and approved the final manuscript. All authors contributed to the article and approved the submitted version.www.aimieditor.com) for the English language editing and review services.The authors thank AiMi Academic Services (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.


To study the risk factors of social anxiety (SA) in essential tremor (ET) patients.Motor, cognition, and SA were evaluated using the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), Mini-Mental State Examination (MMSE), and Liebowitz Social Anxiety Scale (LSAS) for each subject. The potential risk factors of SA in ET were analyzed using univariate analysis.P < 0.001). Female , younger age , and head tremor  were risk factors of SA among ET patients.A total of 80 ET patients and 85 healthy controls completed the evaluation. The LSAS evaluation showed that the prevalence of SA in the ET group was 48.8%, higher than that in controls (12.9%, SA is prevalent in patients with ET. Risk factors, such as female sex, age, and head tremor, should be considered for the prevention and intervention of SA in ET patients. Essential tremor (ET) is the most common movement disorder clinically manifested by postural and kinetic tremors involving the hands, head, and other parts of the body . The preAccording to DSM-IV diagnostic criteria , a diagnMetzer  first obIdentifying patients with risk factors and then giving them adequate attention will facilitate earlier detection and intervention for social-psychological problems, including SA. So far, there were researches reported that age and female may be the risk factors of ET-SA, but the features of tremor  which are more relevant to the ET manifestation, are still not the warning flags to clinicians. In this study, we will try to reveal more risk factors, especially in features of tremor.A total of 88 ET patients were enrolled from the inpatient and outpatient departments of Qujing Second People’s Hospital (in the northeastern part of Yunnan) in about 1.5 year from July 2019 to January 2021. Patients who met the diagnostic criteria for ET according to the Chinese guidelines , were inThree scoring scales were used for evaluation: Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS), with a maximum of 100 points, was used to evaluate the tremor location, operation, and ability of daily living, with a total of 21 items; Mini-Mental State Examination (MMSE), with a maximum of 30 points, was used to evaluate cognitive function, with 11 items. The cognitive function decline standard was illiteracy <17, primary school <20, junior high school, and above <24 . Liebowis), in which the t/t′ test of two independent samples was adopted. The measurement data with non-normal distribution were represented by median and quartile [M (QR)], and the Mann–Whitney U test was used. Logistic regression analysis with the entry method was used to screen for independent variables. The step probability p entry and deletion criteria were 0.05 and 0.10, respectively. P < 0.05 was considered statistically significant.SPSS17.0 statistical software was used for data processing and analysis. The Chi-square test was used to test the composition ratio of the two groups of counting data. The measurement data of normal distribution were expressed as mean ± standard deviation . The prevalence of social anxiety in ET patients (48.8%) was significantly higher (P < 0.001) than that in the control group . The risk of SA in young and middle-aged ET patients was 4.172 times higher than in older adults (P < 0.05). The risk of SA in ET patients with head tremor was 4.707 times higher than in ET patients without head tremor , possibly because inpatients are exposed to more strangers, which increases their exposure to tremor, and therefore prefer to complete their consultations in the outpatient setting.The lifetime prevalence of SA has been reported in various studies, ranging between 3 and 13% , while wOR = 1.09 and 1.13).Not all ET patients experience SA. Our study showed that age, sex, and head tremor were the risk factors for ET-SA. Some studies have measured ET patients using the LSAS scale and found that the degree of ET tremor was positively related to the degree of SA, i.e., patients with higher tremor scores were at higher risk of developing SA , 22. HowOur study showed female ET patients are more likely to have SA. The mechanism may involve the effects of steroid hormones on neural excitability . CompareOur study also suggests that the risk of SA among young and middle-aged ET patients is higher than that in older ET patients. This probably because young ET patients pay more attention to external images . There wSome studies have measured ET patients using the LSAS scale and found that the degree of ET tremor was positively related to the degree of SA, i.e., patients with higher tremor scores were at higher risk of developing SAD , 13, 22.According to our results, physicians can focus on screening female, young and head tremor patients to early reduce the physical and psychological suffering of patients. Early intervention or ET-SA treatment, including active thinking cessation, systemic desensitization, recognition of non-ideal thinking, other cognitive behavioral therapies . TreatmeThis study has some limitations. The small sample size may cause missing possible risk factors in the study. The patient sample from our hospital may introduce some common biases, for example, the patients may be the ones with more pronounced tremor and more impaired quality of life, compared with those patients who didn’t come to hospital. This study is based on hospital patients and may have biases that affect the severity of social anxiety . We did not assess “quality of life” and “disability” in this study which may provide more complete image of impact of SA. Long-term follow-up is needed to reveal the nature course of ET-SA and confirm the effect of early intervention. This is a single-center cross-sectional study based on a local population in northeastern Yunnan Province, China. The need to combine the present results with those of other similar studies due to ethnic and cultural variability and the heterogeneous nature of ET.In conclusion, ET-SA may be not only a neurodegenerative process but also a conditioned emotional response, with connection between motor and non-motor symptoms. This study identified age, sex, and tremor distribution as risk factors of ET-SA. Head tremor is given insufficient attention. ET-SA can be early recognized by using risk factors.The original contributions presented in this study are included in this article/supplementary material, further inquiries can be directed to the corresponding author.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. The patients/participants provided their written informed consent to participate in this study.LH analyzed and interpreted the data and drafted the manuscript. Both authors designed the study, acquire the data, revised the manuscript for important intellectual content, read, and approved the final manuscript.


Conclusions: The low mortality of our series emphasizes the importance of an extensive and immediate surgical drainage of both the neck and the mediastinum. Mediastinal drainage from cervicotomy seems to be a risk factor for post-operative complications. Minimally invasive surgery on the chest cavity, such as with Uniportal-VATS, could be a good approach above all in elderly patients and all those cases where bilateral access is required.Background: Descending necrotizing mediastinitis (DNM) is a severe, life-threatening complication of oropharyngeal infections with cervical necrotizing fasciitis. In this study, we aimed to identify any possible factors that correlate with favorable outcomes. Methods: We retrospectively analyzed our series of 18 patients who underwent surgical treatment for DNM from a cervical abscess. Gender, age, symptoms, etiopathogenesis, comorbidities, time to surgery from diagnosis, degree of diffusion, identified microorganisms, surgical procedure, days in the intensive care unit, need for tracheostomy, complications, and surgical outcomes were reviewed. Results: The main type of surgery was thoracotomy + cervicotomy in eight cases (50.0%), followed by cervicotomy +VATS in four (22.2%). Seven patients (38.9%) had two or more surgeries; a bilateral operation was necessary for four patients. Evaluating the risk factors associated with post-operative complications, age ≥ 60 years ( Descending necrotizing mediastinitis (DNM) is a dangerous and life-threatening form of soft tissue infection with a high mortality rate, even in surgically treated patients. Mediastinitis can usually originate from endoscopic or foreign body perforation, as well as from surgical wounds, in particular post-cardiac surgery and cancer. In some cases, DNM can develop from an odontogenic, oropharyngeal, or cervical abscess; in these cases, it spreads from the soft tissue through the deep and superficial cervical fascial planes to the mediastinum and it disseminates, following gravity and negative pressure, into the chest cavity. Infections from the pharynx, the tonsils, or teeth can affect the retropharyngeal paratracheal, paraoesophageal, prevertebral, posterior mediastinum, and pleural spaces . Delay iAll the series published since 1970 ,5 confirWe retrospectively analyzed our series of 18 patients who were admitted to the emergency room (E.R.) for DNM from a cervical abscess and underwent prompt surgical treatment from January 2012 to February 2022. Patients with acute mediastinitis secondary to esophageal perforation, surgical wound infection, or anastomotic leak were excluded.Gender, age, symptoms, etiopathogenesis, comorbidities , time to surgery from diagnosis, degree of diffusion, identified microorganisms, surgical procedure, days in an intensive care unit (ICU), need for tracheostomy, complications, and surgical outcomes were reviewed.All patients underwent blood tests, electrocardiography, and neck and chest computed tomography (CT). Surgery was performed under general anesthesia and single lung ventilation in the case of thoracic access. Two patients were excluded from surgery for hemodynamic instability and died of septic shock after a few hours.In the suspicion of DNM, the patient promptly underwent a neck and chest CT scan with intravenous iodinated contrast media. In 4 cases, because of the suspicion of pharyngoesophageal perforation, a gastrographin swallow was also performed.Cervical access was an extended “J” shape access along the sternocleidomastoid muscle of the involved side. In the case of bilateral involvement of the cervical compartments, an extended Kocher cervicotomy was performed. At the end of the surgery, drainages were left in place in the cervical compartments of the neck and retrosternal region through the cervical incision. The skin and subcutaneous muscles were often not closed to allow for further daily medications of the neck.The anterior and posterior mediastinum and chest cavity were drained through a V intercostal access or by thoracotomy or Uniportal Video-Assisted Thoracic surgery (VATS). Two  or three (in thoracotomy) drainages were left in place in the mediastinum and pleural space.2 test and Fisher’s exact test were used to compare categorical variables, and Student’s t-test was used to compare continuous variables.Continuous variables were expressed as mean ± standard deviation, and categorical ones as percentage. Pearson’s χp < 0.2 were selected for the Cox proportional hazards regression model to assess prognostic independent factors. For all tests, a p-value < 0.05 was considered statistically significant. Statistical analysis was performed using IBM SPSS Statistics for Macintosh .All the clinical-pathological and surgical variables were tested in univariate analysis to assess prognostic factors. All covariates with Among the studied population, seven (38.9%) patients were males. The median age was 43 years for males (range 23–58 years) and 63 for females (range 41–91 years). Five patients (27.8%) were over 60 years old. Seven patients were referred to our hospital from another hospital with the suspicion of DNM. Etiopathogenesis was odontogenic, peritonsillar, and pharyngeal in nine, seven, and four cases, respectively. The main clinical-pathological characteristics, comorbidities, and symptoms of the patients are reported in Out of the 18 patients, 17 underwent surgery during the first 12 h from admission to the E.R. and one on the first day. One patient was operated after 6 days from the first admission in another hospital: she was a 48 years old woman who had a dental extraction ten days before and that noticed cervical swelling and odynophagia . After oSeven patients were referred to our hospital from another institution for further management and immediately underwent surgery. Usually, they experienced a failure of antibiotic therapy, and for worsening clinical conditions, they performed a CT scan showing a DNM, wherein the individual was immediately transferred to our Emergency Department.The main type of surgical approach as first operation was thoracotomy + cervicotomy in eight cases (50.0%), followed by cervicotomy + VATS in four cases (22.2%). The right side was the most affected side . Seven patients (38.9%) underwent two or more surgeries, for a mean number of re-operations of 2.5 ± 2.7 (1–11); a bilateral operation was necessary for four of the patients. None of the patients who underwent Uniportal-VATS required a second look on the homolateral hemithorax, but two patients required a Uniportal-VATS on the contralateral side.In three cases (16.7%), only a cervicotomy with the insertion of retrosternal drainage in the superior mediastinum was performed without opening the chest cavity.The first was a 36-year-old male who had a left third mandibular molar odontectomy 5 days before the evidence of cheek swelling and pain. He went to another hospital where he was discharged with a prescription for antibiotics and corticosteroids. The day after, he went to our Emergency Department with a voluminous left face swelling and subcutaneous crackling with fever and confusion . After nIn the other cases, the choice of performing mediastinal drainage through the cervical incision was due to the age (85 years old) of the patient in the second case and due to comorbidities (diabetes and autoimmune thrombocytopenia) in the third case. In these cases, DNM was caused by a tonsillar infection and a pharyngeal abscess spreading in the superior mediastinum and anterior mediastinum .All patients required ICU stay, and the time of intubation was 13.9 ± 11.4 (1–41) days. In three cases, a tracheostomy was performed .Eight patients (44.4%) developed post-operative complications  patients died. The first was a diabetic 63-year-old woman who had an arthrodesis for scoliosis 2 years before the DNM from pharyngeal abscess. Despite the cervicotomy and the posterior mediastinal incision in the left thoracotomy and the removal of the infected vertebral pedicle screw, she died of sepsis in the ICU 20 days after thoracic surgery.The second patient was a 91-year-old woman, referred to our hospital for dyspnea in submandibular, cervical, and mediastinal fluid collection from a dental abscess. She underwent cervicotomy and right thoracotomy, but she died of respiratory and renal failure 14 days after surgery.All patients received empiric broad-spectrum antimicrobial therapy including antifungal agents until the lab reports of the intraoperative microbiological examinations became available. Then, targeted therapy began, according to microbiologic results.The main isolated germs were as follows: Streptococci in five cases , Prevotella  in three cases, Lactobacillus casei and paracasei in two cases, and Candida albicans in two cases; other bacteria were Klebsiella pneumoniae, Escherichia coli, Enterococcus fecalis, and Acinetobacter baumanii. In four cases, polymicrobial infections resulted in the cultures. Two patients were negative in the microbiological tests.The total length of in-hospital stay was 31.2 ± 25.9 (9–101) days.Demographic, clinical features and surgical outcomes of patients are listened in No correlation was found between clinical and surgical variables  and total in-hospital stay.p = 0.031), only cervicotomy alone as a surgical approach (p = 0.040) and bilateral approach (p = 0.048) resulted in being significant at univariate analysis, and only age >=60 years (p = 0.04) and cervical approach (p = 0.05) confirmed their significance in terms of the multivariate analysis . The patients with type III were managed with unilateral or bilateral thoracic surgery, recording the highest mortality in the whole group (27.6% vs. 9.4%).In the literature, several papers suggested cervicotomy for limited DNM. In a German series of 45 DNM , formal Moreover, in a recent work including nine patients , a transIn 2010, Karkas et al.  publisheOn the contrary, in a recent work, De Palma et al.  recommenOur results confirmed that the strategy suggested by De Palma et al.  is effecIn the last 6 years, the VATS approach and, in particular, Uniportal-VATS has become the preferred technique for all major thoracic procedures in our department ; therefoAccording to more recent literature , we consCompared to mediastinal drainage from cervicotomy, VATS has the advantage of exploring the entire chest cavity and to place the drainages under visualization into the pleural collections with a very low traumatic impairment. At the same time, since the right chest cavity is usually firstly involved in the DNM, in the case of contralateral spread, a Uniportal-VATS approach is feasible with all the advantages of lower invasiveness.Three out of the four patients requiring contralateral lung surgery had post-operative complications . A bilateral approach was necessary for two patients with stage II according to Guan’s classification, one with stage I one with stage III. In no case did we perform a bilateral approach during the first operation. All the patients had a first operation on the right side and a second operation on the left side. This means that the CT scan performed after the operation showed a progression of the disease and an involvement of the controlateral hemithorax. In our results, a bilateral approach, even if only at univariate analysis, is a risk factor for post-operative complications, due to both the worsening of the mediastinal involvement and the impact of the functional respiratory impairment, which consequently entails a longer hospitalization in the ICU.In the last years, we switched from a more conservative surgical policy (only cervicostomy) to a more aggressive one, despite being performed through mini-invasive Uniportal thoracoscopic approaches; this approach could also be offered to elderly patients in a situation of intensive multiparametric management because these patients are at high risk of major complications or death.n = 8) or the clamshell (n = 8) approach, with a mortality rate of 12.5% . Although the authors did not correlate the cause of the exitus with the technical choice of surgery, we consider this approach at risk for osteomyelitis and dehiscence of the sternum; furthermore, it seems not so suitable for draining the infero-posterior mediastinum collections, even when performed in single-lung ventilation.However, some authors ,17 prefeIn this study, we attempted to identify clinical factors able to predict post-operative complications with the aim of suggesting to physicians which patients deserve more intensive care and multidisciplinary management (because of those more at risk for post-op complications). Older patients and patients treated by cervicostomy presented a significantly higher number of post-operative complications.Despite the main limitations of our work, related to small sample size and the retrospective nature of the study, which prevent the analysis to drive strong conclusions, we report the results of a quite large series compared to other studies ,13,16,17Our good results can be probably explained by a multidisciplinary, prompt, and aggressive management of the patient in the first hours by intensivists, thoracic surgeons, anesthesiologists, otolaryngologists, and dentists; another reason was the integrated treatments with our infectivologists in the post-operative period, which added the benefit of target antibiotic therapies to daily surgical medication of the neck through the cervicotomy kept open. All drainages were taken in place and washed with physiological solution until their tribute was clear without purulent material. This meticulous management added to the long recovery period of the illness itself, explaining the long hospitalizations of 31.2 ± 25.9 days (9–101).p = 0.032). Although in our study tracheotomy was not a significant risk factor for mortality, one of the three patients who died in ICU underwent a tracheotomy. As in Kim’s series, in our report, patients with early tracheotomy experienced a prolonged hospital stay due to contamination of the pretracheal space requiring a flap for tracheo-cutaneous fistula closure. For this reason, we believe that tracheotomy should be performed with great caution in patients with DNM.Another point of strength in our results is the low rate of tracheotomy (16.9%) compared to the reported 60% of other series . On thisOn the basis of multivariate analysis, we suggest avoiding mediastinal drainage from cervicotomy or reserving this approach for very limited antero-superior mediastinitis, since a non-invasive surgery could improve the survival in DNM patients, without impairing complications and long stay hospitalization.DNM is a life-threatening condition that requires timely multidisciplinary management, with prompt and aggressive surgical treatment.Standard treatment consists of cervicotomy to drain the source of infection, as well as an open approach to the thorax (either thoracotomy or sternotomy). Minimally invasive surgery on the chest cavity, such as in Uniportal-VATS in our experience, provides good exposure in order to clean the mediastinum and pleural cavity, with the advantages of reduced invasiveness, above all in elderly patients, and all those cases where bilateral access is required. This approach could also be offered to elderly patients in intensive multiparametric management because this group resulted a in having a high risk of major complications or death.Further multicenter and randomized studies must take place in the future to drive stronger conclusions, identifying potential risk factors in clinical characteristics of patients or surgical approaches that may help clinicians in providing the most appropriate treatment for this quite rare but severe condition.


Sleep disorders and reduced physical activity are common in patients with psychosis and can be related to health-related outcomes such as symptomatology and functioning. Mobile health technologies and wearable sensor methods enable continuous and simultaneous monitoring of physical activity, sleep, and symptoms in one’s day-to-day environment. Only a few studies have applied simultaneous assessment of these parameters. Therefore, we aimed to examine the feasibility of the simultaneous monitoring of physical activity, sleep, and symptoms and functioning in psychosis.Thirty three outpatients diagnosed with a schizophrenia or other psychotic disorder used an actigraphy watch and experience sampling method (ESM) smartphone app for 7 consecutive days to monitor physical activity, sleep, symptoms, and functioning. Participants wore the actigraphy watch during day and night and completed multiple short questionnaires  on their phone. Hereafter they completed evaluation questionnaires.Of the 33 patients , 32 (97.0%) used the ESM and actigraphy during the instructed timeframe. ESM response was good: 64.0% for the daily, 90.6% for morning, and 82.6% for evening questionnaire(s). Participants were positive about the use of actigraphy and ESM.The combination of wrist-worn actigraphy and smartphone-based ESM is feasible and acceptable in outpatients with psychosis. These novel methods can help both clinical practice and future research to gain more valid insight into physical activity and sleep as biobehavioral markers linked to psychopathological symptoms and functioning in psychosis. This can be used to investigate relationships between these outcomes and thereby improve individualized treatment and prediction. People with schizophrenia spectrum disorders lack physical activity, which is not only a major contributor to poor physical health and premature mortality , 2, but Considering these clinically relevant relationships, improved assessment of physical activity and sleep patterns as biobehavioral markers in psychosis is highly needed , 12. EspActigraphy is a non-invasive method, mostly worn as an actigraphy monitor on the wrist, that allows for continuous and precise assessment of sleep patterns  and physical activity  . SeveralActigraphy measurement of sleep and motor activity can be combined with the smartphone-based Experience Sampling Method (ESM) to allow the collection of ecologically valid daily-life self-report data. ESM is a validated, digital diary method that consists of multiple repeated measurements throughout the day, using short questionnaires that patients can complete using a smartphone application , 29. In Combining actigraphy with ESM facilitates the examination of the direct relationships between physical activity, sleep, and symptoms in daily life. Only a few studies used a combination of actigraphy and ESM for the assessment of physical activity or sleep in relation to symptomatology in schizophrenia populations. One study found that actigraphy-measured spontaneous motor activity was an objective readout of apathy in patients with schizophrenia . Two othConsidering these promising applications of ESM and actigraphy for psychiatry research, it is important to establish the clinical acceptability and feasibility of these methods for psychiatric patients before implementing them into research and clinical practice. This study aims to examine the feasibility of the combination of actigraphy and ESM to measure physical activity, sleep, and daily life symptoms in patients with schizophrenia spectrum disorders and seeks to provide guidance for feature actigraphy/ESM studies.2.2.1.Patients with a schizophrenia spectrum disorder diagnosis were included from June 2020 to October 2022 in the outpatient departments of the mental health care institution GGz Central, the Netherlands. Inclusion criteria were: (i) age 16–65 years; (ii) a diagnosis of schizophrenia-spectrum disorder, i.e., schizophrenia, schizoaffective, schizophreniform, or brief psychotic disorder according to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) ; (iii) g2.2.A comprehensive assessment of psychopathology, social functioning, quality of life, and neurological functioning was performed, which can be found in the 2.3.Participants were instructed to use an ESM smartphone application, Psymate™,2.4.Physical activity, sleep, and circadian rhythm were measured by actigraphy using the MotionWatch8 , a wrist-worn device that contains a tri-axial accelerometer that is validated for measuring physical activity and sleep in clinical and non-clinical populations , 43. Par2.5.In order to assess the feasibility and compliance of the combined assessments of actigraphy and ESM, descriptive analyses of actigraphy and ESM outcomes were conducted. For actigraphy, the wear time within the instructed timeframe was calculated. For ESM, response and completion rates of the ESM morning, evening and daily questionnaires were calculated. To evaluate the burden of each continuous questionnaire, the item “this beep disturbed me” was included in the daily questionnaire. We analyzed means, standard deviations and distributions for this ESM item and the answers on the evaluation questionnaire. All statistical analyses were performed with R version 4.2.0 .3.3.1.n = 25, 75.8%) and between 25 and 51 years old . Patients had relatively low psychiatric symptom severity, with mean BPRS total and positive symptoms scores of 48.4 (SD = 11.7), and 12.9 (SD = 4.5), respectively. The majority of patients were unemployed  and had serious impairments in social functioning . Demographic and clinical characteristics are presented in We included 33 participants, who were mainly male (3.2.Participants used the actigraphy watch for a mean duration of 7 days and 1 h (SD = 23 h), within the instructed timeframe of 7 days and 14 h . One of them did not use actigraphy simultaneously with the ESM app, but, after re-instructions, did wear the actigraphy watch for 3 days following the 7-day period of ESM assessments. Answers from the evaluation questionnaire (ranged 1–7) showed that the wrist actigraphy watch was mostly comfortable to wear during day  and night  and did not impair daily activities . In general, patients were not bothered by wearing the actigraphy watch visible to others . However, participants were moderately motivated to wear the actigraphy device for a longer period .3.3.The mean completion rates of the ESM were 64.0%  for the continuous questionnaires, 90.6%  for the morning questionnaires and 82.6%  for the evening questionnaires. The ESM item “this beep disturbed me” was rated with a mean of 2.3  on a scale from 1 to 7. Answers from the evaluation questionnaires showed that participants did not experience difficulties using the ESM application  or understanding the ESM questions . Overall, participants found the number  and duration  of beep questionnaires not too burdensome.4.This study demonstrates that the combination of wrist-worn actigraphy and smartphone-based ESM is a feasible and acceptable method for outpatients with schizophrenia or other psychotic disorder with moderate to serious impairments in social functioning. Participants used the actigraphy watch during the instructed timeframe and completed the majority of the ESM beep questionnaires on their smartphones. Also, they positively evaluated the burden and user-friendliness of ESM and actigraphy.The application of ESM and actigraphy in populations with psychosis may provide valuable clinical information and new insights for future research and treatment since sleep and physical activity patterns are important biobehavioral features related to psychopathological symptoms and functional outcomes in patients with psychotic and other psychiatric disorders , 8, 9. SThe combined approach of ESM and actigraphy, or other wearable sensors, offers several advantages over ESM alone. Wearable sensors offer the possibility for passive, non-intrusive (not requiring user action) and continuous data collection, contrary to interval-based ESM questionnaires that require the participant’s action and compliance. Although earlier ESM feasibility studies showed that ESM only minimally interfered with daily life routines and had no psychological adverse effects , 51, 52,Since mobile and wearable sensor technologies are relatively new in psychiatric research, only a few studies used the combination of ESM and actigraphy in patients with psychotic disorders for either examination of sleep , 34 or pn = 1,717 individuals with different mental health conditions) that used a paper-and-pencil diary in combination with a beep-producing digital watch (10 beeps per day during 4–6 days) showed that persons with psychosis  had response rates of 70%, and were therefore less compliant than healthy participants   . An ESM < 0.001) . Hospita< 0.001) , 40. The< 0.001) . Compare< 0.001) .n = 184) of long-stay inpatients , various studies have demonstrated its usability in populations with psychosis or other severe mental illness, for example, in a large sample n = 4 of longFrom a scientific perspective, long-term periods of monitoring with high sampling frequencies seem attractive for the collection of large amounts of data, but burden to the patient, user-experiences and clinical feasibility are often neglected. It is important to establish the optimum ESM and actigraphy intensity and/or duration for the implementation of these methods in psychiatric research and clinical practice. The current feasibility study is in line with ESM guidance papers, where a typical design of 6–7 days with a sampling frequency of 10 questionnaires per day is proposed , 31, 54.4.1.Some limitations should be noted. First, considering the small sample size of patients with a relatively stable psychiatric condition, the generalizability of the study should be interpreted with caution. However, for the inclusion of patients, no restrictions were made on the stage of the disease, symptom severity or substance abuse, to obtain a diverse sample of patients with schizophrenia spectrum disorders. Furthermore, the low psychotic symptom severity scores in the sample do not necessarily mean that the sample is not representative; understandably, patients who are relatively stable and treatment compliant want to participate in such a study. Therefore, the sample represents patients for whom these novel developments can be used in clinical practice. Furthermore, the stable condition of patients offers the possibility of a longer duration of sampling and intensive measurement of symptomatic, behavioral, and environmental factors. Second, we assessed the feasibility and acceptability of a specific sampling duration  and frequency , and therefore cannot extrapolate our results to longer durations of monitoring or more intensive sampling frequencies. Previous ESM studies have demonstrated that a sampling duration of up to 10 days with a sampling frequency of 8–10 questionnaires per day is acceptable for the collection of ecologically valid data in psychosis research , 29, 31.4.2.The application and interpretation of this “real-world” data for clinical research faces several challenges . First, 5.The combination of ESM and actigraphy is a feasible and acceptable method for patients with psychosis. It can be used for the collection of real-world, ecologically valid, (semi) continuous data on sleep patterns, physical activity, and daily life symptoms, can offer new and valuable insights into the relationships between sleep, activity, psychopathology, and functioning. As mobile technologies are ubiquitous, also in psychiatric populations, these novel methods can be easily implemented in clinical and research practice and pave the way for psychosis prediction, new (early) intervention targets, and personalized treatment.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 Medical Ethical Committee of Maastricht University. The patients/participants provided their written informed consent to participate in this study.LP, JD, PD, and PH: conceptualization and methodology. LP and SV: data curation, formal analysis, investigation, and visualization. LP, JD, and PH: project administration. PD and PH: resources. JD, PD, and PH: supervision. LP: writing—original draft. JD, PD, PH, and SV: writing—review and editing. 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.https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1107812/full#supplementary-materialThe Supplementary material for this article can be found online at: Click here for additional data file.


Post-stroke fatigue (PSF) is a common complication in the patients with acute ischemic stroke (AIS). This prospective study aimed to investigate the relationship between red blood cell distribution width (RDW) at admission and PSF in the acute phase.The AIS patients were enrolled in Nantong Third People's Hospital, consecutively. PSF in the acute phase was scored according to the Fatigue Severity Scale. Levels of RDW were measured at admission. The associations were analyzed using multivariate regression and restricted cubic splines (RCS).P = 0.006). The linear dose-response associations of RDW with PSF in the acute phase were found, based on the RCS model . These results remained significant in other models.From April 2021 to March 2022, a total of 206 AIS patients  were recruited. After the adjustment for potential confounding factors, RDW at admission remained the independent associated factor with PSF in the acute phase (OR [odds ratio], 1.635; 95% CI [confidence interval], 1.153–2.318; RDW at admission could serve as a novel biomarker of PSF in the acute phase of AIS. Stroke is one of the vital reasons for global disease burden –3. AcuteRed blood cell distribution width (RDW), which could be obtained from routine blood testing, is an easily accessible biomarker. According to previous studies, RDW is able to reflect the variability in volumes of peripheral red blood cells and associated with inflammation , 13. In Nevertheless, to our knowledge, there is no research about the relationship between the levels of RDW at admission and PSF in AIS patients. Hence, our prospective study was designed to assess the role of RDW on PSF in the acute phase.From April 2021 to March 2022, the AIS patients were enrolled in our study from the Nantong Third People's Hospital, consecutively and prospectively.The inclusion criteria were listed as follows:Onset within 7 days;Age≥18 years;With sufficient cognitive ability;With sufficient knowledge of the Mandarin Chinese language and Nantong local dialect.The exclusion criteria were listed as follows:Pre-stroke fatigue;Incomplete data;Refuse to participate in the research;Poor mental state.This study was registered with China clinical trial registration center (Registration number: ChiCTR2100044165), approved by the ethics committee of Nantong Third People's hospital (Ethics number: EK2021008), and performed according to the principles of the Declaration of Helsinki.via Hamilton Anxiety Scale (HAMA). The levels of RDW at admission were measured within 24 h after admission.The clinical assessments were completed in a separate conversation room. We collected general demographic questionnaires (age and sex), past medical history , clinical data  and laboratory parameters . Stroke severity was assessed by National Institute of Health stroke scale (NIHSS). Anxiety severity was assessed PSF was assessed by the Fatigue Severity Scale (FSS) within 2 weeks after onset of ischemic stroke. FSS consists of 9 items, each item according to the patient's evaluation of fatigue severity will gradually transition the result to 1–7 points. The higher the score, the more severe PSF. We took the total score of 36 as the dividing line (http://www.r-project.org) was used to conduct statistical analyses. Categorical variables are expressed as n (percentages). Normally distributed variables are expressed as the mean ± SD, and abnormally distributed continuous variables are expressed as medians (interquartile range [IQR]). The differences between PSF group and non-PSF group were identified with the Student's t-test, the Wilcoxon W-test, the chi-square test or Fisher's exact test as appropriate. The violin plot was utilized to present the distribution of RDW between the PSF group and the non-PSF group. We explored the relationship between RDW and PSF in different logistic regression models. Model 1 was unadjusted model. Model 2 was adjusted for age and sex. Model 3 was adjusted for age, sex, coronary heart disease and baseline NIHSS score. Model 4 was adjusted for age, sex, coronary heart disease, NIHSS score and HAMA score. What is more, we used restricted cubic splines (RCS) with three knots placed at the 10th, 50th, and 90th percentiles to evaluate the dose-response relationship of RDW with PSF in different models. P < 0.05 was considered statistically significant.R software ; Incomplete data (n = 7); Refuse to participate in the research (n = 8); Poor mental state (n = 4)  . Finallyn = 70) were more likely to have higher proportion of coronary heart disease (P = 0.026), elevated levels of NIHSS score (P = 0.036), HAMA score (P = 0.001) and RDW (P = 0.023). P = 0.023).P = 0.005). After the adjustment for age and sex (model 2), RDW might also be the related factor to PSF . After the adjustment for age, sex, coronary heart disease and baseline NIHSS score (model 3), the OR of PSF for RDW was 1.517 . What is more, in the model 4, which included age, sex, coronary heart disease, NIHSS score and HAMA score, RDW remained the independent associated factor with PSF .P for non-linearity = 0.312; P for linearity = 0.019; P for non-linearity = 0.351; P for linearity = 0.022; P for non-linearity = 0.372; P for linearity = 0.037; In this prospective observational study, we have found that RDW at admission could be one independent associated factor with PSF in the acute phase of AIS, according to the results of different logistic regression models. In addition, based on the RCS models, the linear dose-response associations of RDW with PSF in the acute phase were confirmed.The incidence of PSF in the acute phase is 34.0 % in our study, which is in line with previous studies –11. Thisvia interleukin-6  and tumor necrosis factor-α (TNF-α).In short, this prospective observational study is the first study centering on the relationship between RDW at admission and PSF in the acute phase of AIS, as far as we know. Linear dose-response associations of RDW with PSF in the acute phase of AIS have been found. Consequently, RDW at admission may be a novel biomarker of PSF in the acute phase, which is helpful for neurologists. Nevertheless, the study with large sample is required in the future, and these conclusions need to be verified in other stroke centers.The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by the Ethics Committee of Nantong Third People's hospital (Ethics number: EK2021008). The patients/participants provided their written informed consent to participate in this study.MP wrote the manuscript and performed the statistical analyses. YuC collected the data and assisted with writing the manuscript. YaC, KF, HS, HH, WZ, HZ, and JJ collected the data. All authors contributed to the article and approved the submitted version.This study was supported by Social and People's Livelihood Science and Technology Innovation Special Project in Nantong City (ms12021065).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.


Objective This study aimed to evaluate the diagnostic profile of breast cancer cases during the coronavirus disease 2019 (COVID-19) pandemic compared with the previous year.Methods It is a retrospective study of cases diagnosed by a reference service in the public health system of Campinas, SP, Brazil. Two periods were analyzed: March to October 2019 (preCOVID period) and March to October 2020 (COVID-period). All women diagnosed during the periods were included. The Chi-Squared or Fisher exact and Mann-Whitney tests were used.Results In the preCOVID and COVID periods, breast cancers were diagnosed, respectively, in 115 vs 59 women, and the mean ages at diagnosis were 55 and 57 years (p = 0.339). In the COVID period, the family history of breast cancer was more observed , cases were more frequently symptomatic  and had more frequently palpable masses . In symptomatic women, the mean number of days from symptom to mammography were 233.6 (458.3) in 2019 and 152.1 (151.5) in 2020 (p = 0.871). Among invasive tumors, the proportion of breast cancers in stages I and II was slightly higher in the COVID period, although not significantly . Also in the COVID period, the frequency of luminal A-like tumors was lower , of triple-negative tumors was twice as high , and of estrogen receptor-positive tumors was lower .Conclusion During the COVID-19 pandemic, breast cancer diagnoses were reduced. Cases detected were suggestive of a worse prognosis: symptomatic women with palpable masses and more aggressive subtypes. Indolent tumors were those more sensitive to the interruption in screening. The coronavirus disease 2019 (COVID-19) pandemic has had unprecedented effects on healthcare systems worldwide, and the impact on cancer care is being predicted from the outset.At the beginning of the pandemic, there were international recommendations to discuss the option of postponing surgical treatment until the pandemic was under better control, according to the risk/benefit ratio. In Brazil, the recommendation published by the Society of Clinical Oncology in May 2020 recommended for newly diagnosed breast cancer, initiation of systemic treatment with neoadjuvant endocrine therapy or neoadjuvant chemotherapy, with anti-HER2 blockade if the disease was HER2 positive. In postmenopausal patients and luminal A-like cancer cases, including clinical stages I and II, neoadjuvant endocrine therapy and surgery after 3 to 4 months, or when appropriate, if responsive, were options to be considered.In Brazil and other middle-income countries, there is inequity in access to screening tests, cancer detection and breast cancer treatment.There is a suspicion that the pandemic would impact deepening inequalities in cancer care.This study aimed to evaluate the diagnostic profile of breast cancer cases during the COVID-19 pandemic in users of the public health system in a populous urban city in Brazil, compared with the same period of the previous year. Clinical and pathological characteristics were analyzed. Diagnostic profiling studies can help to predict delays and better allocation of limited resources, targeting better effects on cancer outcomes, especially in public health systems.It is a retrospective descriptive study of breast cancer cases diagnosed by the leading reference service for diagnosing breast cancer in the public health system in Campinas, state of São Paulo, Brazil. Two periods were analyzed: March 1st to October 31st, 2019, preCOVID period, and March 1st to October 31st, 2020, when the COVID-19 worldwide pandemic was in full force. All women who were diagnosed at the service during the analyzed periods were included.About half of the city's women depend exclusively on the public health system, which performs free-of-charge screening, diagnosis and treatment, at different levels of complexity of the services.i-67% (positive when over 20%)Mammograms were performed using digital devices with complements. Biopsies were performed by core needle guided by ultrasound or stereotaxy. A central laboratory performs the histopathological and immunohistochemical analyses with direct links. The classification of tumor subtypes was based on hormone receptors (positive when above 1%), KThe study data were collected and managed through the service's information system, which uses electronic data capture via REDCap, hosted by the institution that maintains the unit. The compiled data form contains information about the patient's age (in complete years), presence or absence of symptoms, menopausal status and family history of breast cancer. Results of mammograms, biopsies, immunohistochemistry, HER2 and clinical staging were also registered.p < 0.05.To describe the sample profile according to the variables under study, frequency tables of categorical variables were drawn up, with absolute frequency (n) and percentage (%) values. Descriptive statistics of numerical variables were presented by mean and standard deviation (SD) values. To compare categorical variables between periods were used the Chi-squared or Fisher exact tests. To compare the numerical variables between periods, the Mann-Whitney test (2 groups) was used due to the absence of normal distribution of the variables. The significance level adopted for the statistical tests was 5%, that is,The ethics committee of the Universidade Estadual de Campinas, under the number CAAE 89399018.2.0000.5404 approved the study “Population-based assessment of breast cancer screening, diagnosis and death of women in the city of Campinas according to age”, ongoing since 2018. The Committee waived the need for consent due to the retrospective nature of the study.p = 0.339). The menopausal status of diagnosed women was not different between the periods (p = 0.260). However, a family history of breast cancer was more present in the COVID period  (p < 0.001), women had more palpable masses  and were diagnosed through diagnostic mammograms . For symptomatic women, the mean days from symptom onset to mammography was 233.6 days (SD 458.3) in 2019 and 152.1 days (151.5) in 2020 (p = 0.871) (p = 0.193). Among invasive tumors, the proportion of breast cancers in stages I and II was slightly higher in the COVID period but not significant   and 57 years in 2020 (SD = 12) ( 0.001) . Tumour 0.871) . The st 0.428) .p = 0.032). The cases diagnosed were more frequently symptomatic , women had palpable masses more frequently  and were diagnosed through diagnostic mammograms   .p = 0.018). The frequency of triple-negative tumors was twice as high in the pandemic than in the pre-pandemic period . The frequency of estrogen receptor-positive tumors in the pandemic was lower . The other morphological characteristics evaluated did not show significant variation in the period  and those with palpable masses . Most cases were diagnosed through diagnostic mammograms . This was probably due to the interruption of screening activities, with priority access to cases of clinical suspicion. It is interesting to note that patients with a family history of breast cancer were also prioritized in the diagnosis , indicating greater awareness in seeking out the health system.In the pandemic period, diagnosis was more frequent in symptomatic women .The 48.7% reduction in breast cancer diagnosis was mainly at the expense of reducing screening, maintaining access to symptomatic patients. The number of cases diagnosed in symptomatic patients dropped from 58 to 47, a 23% reduction, and cases diagnosed through diagnostic mammograms dropped from 54 to 48, a 13% reduction. In fact, the proportion of in situ tumors, which represents the cases diagnosed through mammography, decreased from 21.7 to 13.6% in the period . Although the difference was not significant, a possible time reduction may reflect easier access to symptomatic patients since the practice of regular screening was reduced. In Canada, a referenced care unit for breast cancer diagnosis changed its structure to rapid diagnostic unit during the pandemic and observed a significant reduction in the time between the mammogram and the final diagnosis.For symptomatic women, the mean days from symptom onset to mammography was 233.6 days (SD 458.3) in 2019 and 152.1 days (151.5) in 2020 (p = 0.428). The subanalysis of the 110 cases diagnosed in stages I and II revealed that the pandemic seems to have selected the same pattern of cases for diagnosis, regardless of stage: cases were observed in symptomatic women and in those with familial history of breast cancer. An analysis from Turkey with 148 patients demonstrated increased tumor size and axillary involvement in the COVID period.Among the invasive tumors, the stage profile was not different between the periods. The proportion of early breast cancers was slightly higher in the COVID period but not significant , as was the frequency of tumors with positive estrogen receptors . The frequency of triple-negative tumors was twice as high in the COVID period, although not significantly , probably due to the small number of cases analyzed.In the COVID period, the frequency of luminal A-like tumors was lower  or presence (B) of the human epidermal growth factor 2 (HER2) protein overexpression and high expression of the KThe reduction observed in luminal A-like tumors and the increase, albeit not significant, in triple-negative tumors indicate that the impact of the pandemic was more observed in the group of more indolent growth ones. This study showed that tumors with a more aggressive profile were the ones more frequently diagnosed. It supports the evidence that indolent tumors have greater sensitivity to screening.The strength of this study was the availability of data in a high-quality information database, an uncommon event in low- and middle-income regions. As the service audited is the largest reference service in a populous city in Brazil, it reflects the population living in similar regions. The main limitation is the reduced observation time, which makes more robust analyses difficult due to the number of cases. It was also not possible to assess the evolution of the cases.During the COVID-19 pandemic, a reduction in breast cancer diagnoses was observed. Cases detected were suggestive of a worse prognosis: symptomatic women with palpable masses and more aggressive subtypes. Indolent tumors were those more affected by the interruption in screening.


Chronic heart failure (CHF) is a major public health concern, as it is associated with poor prognosis and heavy financial burden. In recent years, there has been increasing interest in medications for CHF in China, but few studies pay attention to the effects of nutrition and infection.This was a retrospective study collected patients with CHF admitted to the Department of Cardiology of Qilu Hospital of Shandong University from January 2017 to May 2018. Patients were classified according to the prognosis and the financial burden. Through comparison and regression analysis, we found that the factor associated with worse prognosis were decreased heart rate, albumin and prealbumin; β-blockers and mineralocorticoid receptor antagonism (MRA) were the factor improved the prognosis of patients with CHF; the factor overburdening financial condition were infection, decreased prealbumin, high Alanine aminotransferase (ALT), usage of recombinant human brain natriuretic peptide (rhBNP) and Levosimendan; aspirin and Sacubitril/Valsartan were the factor releasing financial burden of patients with CHF. Then, we grouped by Controlling Nutritional Status (CONUT) score, which enabled evaluation of the patient's protein reserve and immune defenses. Patients in the malnutrition group had higher infection ratios, longer hospital stays, and greater hospital expenses than the normal group. The improvement ratios of therapeutic outcomes in the moderate or severe malnutrition group were lower than in the normal and mild malnutrition group.Malnutrition and infection caused poor prognosis and increased financial burden of patients with CHF. The high CONUT score indicated the CHF patient's unfavorable prognosis and heavy financial burden. Heart failure (HF) is a chronic, serious, spontaneously progressive cardiovascular disease which is the end stage of many heart diseases, including ischemic heart disease, hypertension, dilated cardiomyopathy, and heart valve disease. It was clear that HF had been growing public health problem in China as a result of aging of the population and improving survival of patients with coronary artery disease . From thPharmacotherapy is recommended as the first line therapy on CHF , 9. But Controlling Nutritional Status (CONUT) is a scoring system that is used to assess the host's nutrition and immune states . CONUT iA total of 500 cases with CHF which were admitted to the Department of Cardiology of Qilu Hospital of Shandong University from January 2017 to May 2018 were collected in our study. The selection criteria were established: (1) There were symptoms and signs of typical HF, such as dyspnea, fatigue, fluid retention, wet rales in the lungs, etc; (2) At least one auxiliary examination reflecting cardiac structure and/or function supported the diagnosis of HF, such as cardiac ultrasound or N-terminal-pro-B-type natriuretic peptide (NT-proBNP) ≥125 pg/mL; (3) Duration of disease ≥3 months. Exclusion criteria: (1) Age <18 years. (2) Automatic discharge or death within 24 h of admission.We determined the patient's therapeutic outcomes by comparing the patient's condition, cardiac ultrasound, and NT-proBNP levels on admission with on discharge. Death, transfer to ICU or against advise discharge due to deterioration of heart condition, cardiac ultrasonic ejection fraction decreases or NT-proBNP increase before discharge, the above conditions were divided into deterioration group. Contrary to the above conditions were divided into improvement group. According to CONUT score, patients are divided into normal group (0–1), mild malnutrition group (2–4), moderate or severe malnutrition group (>5) . The patt-test. If data were skewed, median and interquartile range (IQR) were used, and the comparison between the two groups used the rank sum test. Counting data were described as frequency and percentage, and chi-square test was used for comparison between the two groups. Risk factors were analyzed by non-conditional logistic regression analysis, and influencing factors of re-admission interval were analyzed by linear regression. All tests were two-sided, and the differences were statistically significant at p < 0.05.SPSS 20.0 statistical software was used for analysis. If data conforming to the normal distribution, mean and standard deviation (SD) were used, and comparison between the two groups was performed by independent sample A total of 500 hospitalized cases with CHF were included in our study. Patients' mean age was 64.8 ± 14.8 years. Among the etiologies of HF, ischemic heart disease accounted for the highest proportion, followed by hypertension. Among the inducements of HF, infection accounted for the highest proportion. Among the auxiliary examinations to assess the condition of patients with CHF, the use of ECG accounted for the highest proportion. During and after hospitalization, diuretics were used most frequently, followed by mineralocorticoid receptor antagonism (MRA), β-blockers, angiotensin converting enzyme inhibitor (ACEI), and angiotensin II receptor blocker (ARB) .The readmission interval represents the frequency of patient's deterioration in a period of time. Our study used therapeutic outcomes and readmission interval to assess the long term prognosis of patients with CHF.p < 0.05), and neutrophil and NT-proBNP were higher (p < 0.05). The usage ratios of ACEI/ARB, β-blockers, and levosimendan were lower in the worsening group (p < 0.05), and cedilanid was higher . The sensitivity was 0.690 and the specificity was 0.550, respectively .The median readmission interval for patients with CHF was 68.5 days. Linear regression analysis was performed with the readmissions interval as the dependent variable, and basic information, laboratory results, medicine as independent variables. The results showed that: heart rate, prealbumin, and usage of MRA were positively correlated with the hospital interval of patients with CHF .Patients with CHF needed professional caregiver or family member to take care of them. Hospital stays represent the cost of professional caregiver or family member. Therefore, in addition to hospital expenses, hospital stays were also used to assess the financial burden of patients with CHF.p < 0.05). The levels of Aspartate aminotransferase (AST), alkaline phosphatase (AKP), lactate dehydrogenase (LDH), neutrophil, NT-proBNP were higher (p < 0.05), and albumin, hemoglobin were lower (p < 0.05). In terms of medicine, the ratios of diuretics, recombinant human brain natriuretic peptide (rhBNP) were higher in the long hospital stays group than in the short hospital stays group (p < 0.05). The ratios of aspirin was lower in the long hospital stays group (p < 0.05)  .Logistic regression was performed using the hospital stays of patients with CHF as the dependent variable, and basic information, laboratory results, medicine as independent variables. The results suggested that infection, high ALT, and usage of rhBNP were risk factors for prolonging the hospital stays of patients with CHF. The usage of aspirin and Sacubitril/Valsartan were protective factors for shortening the hospital stays of patients with CHF .p < 0.05). The levels of AKP, creatinine(Cr), blood urea nitrogen(BUN), LDH, neutrophil, NT-proBNP were higher (p < 0.05), and Total cholesterol(TC), prealbumin, albumin, lymphocyte, red blood cell(RBC), and hemoglobin were lower (p < 0.05). In terms of medicine, the rates of diuretics, cedilanid, and rhBNP were higher in high hospital expenses group than in low hospital expenses group (p < 0.05)  .Logistic regression was performed using the hospital expenses of patients with CHF as the dependent variable, and basic information, laboratory results, medicine as independent variables. The results suggested that infection, usage of rhBNP and high LDH were risk factors that increased the hospital expenses for patients with CHF, while the use of Sacubitril/Valsartan and high prealbumin were protective factors for reducing hospital expenses of for patients with CHF .p < 0.05). Compared with the normal and mild malnutrition group, the usage ratio of ACEI/ARB, β-blocker in the moderate or malnutrition group were lower, the usage ratio of Cedilanid and rhBNP in the moderate or severe malnutrition group were higher. In terms of prognosis, the ratios of improvement in the moderate or severe malnutrition group was lower than in the normal and mild malnutrition group (p < 0.05). In terms of financial burden, the hospital stays and hospital expenses in the malnutrition group was higher than in the normal group (p < 0.05)  .Our study assessed the associations between nutrition, infection and prognosis, financial burden, and proved that COUNT was also applicable to evaluate the prognosis and financial burden of CHF inpatients in China.“Golden Triangle” medicines-ACEI/ARB, β-blockers and MRA was called the cornerstone of CHF treatment . Usage rIn the regression analysis, our research indicated that low albumin caused poor therapeutic outcomes, while low prealbumin increased hospital expenses and shortened the readmission interval, namely increased the frequency of hospitalizations within the same time. As a protein synthesized in the liver, albumin was an indispensable indicator for clinical evaluation of patients' nutritional status , 25. PreInfection is a common cause of hospitalization in patients with CHF, especially respiratory infection , 30. In We hope finding a score enabled evaluation of the patient's protein reserve and immune defenses. CONUT compounded this requirement. It was calculated on three parameters, the serum albumin and total cholesterol levels and the total lymphocyte count. CONUT is usually used to evaluate the prognosis of cancer patients, , 36. OurRhBNP had the risk of increasing the financial burden of CHF inpatients with moderate or severe malnutrition in our study. The reason may be related to its special mode of administration. Clinically, most drugs treated HF were administered orally, but CHF inpatients with moderate or severe malnutrition were prone to acute exacerbations. For these patients, rhBNP was usually administered intravenously for 3–5 days. Naturally, used rhBNP inpatient's hospital stays was longer and the hospital expenses was higher.Our study still had some limitations. First, there was no distinction between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), and there were differences in therapeutic method and prognosis between HFpEF and HFrEF. However, the majority of patients undergoing cardiac ultrasound in our study were HFrEF which accounted for 69.7%. The HFpEF accounted for only 21.6%, and another 8.7% of patients were heart failure with a moderately reduced ejection fraction (HFmrEF). Second, information was collected only during the hospitalization of patients with CHF, and there was a lack of follow-up data for out-of-hospital treatment. However, during hospitalization, the patients had the most standard therapeutic schedule and the best compliance owing to supervision of doctors and nurses. It was more conducive to the analysis of influencing factors outside of medication. Third, there may be selection bias in single-center study.In conclusion, nutrition and infection significantly affected prognosis and financial burden of patients with CHF. The CONUT score, as a screening tool for assessing the nutritional and immune status of CHF patients, predicted the CHF patient's prognosis and future financial burden.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.LH, Z-HW, WZ, and MZ contributed to conception and design of the study. XJ organized the database. X-lY and BL performed the statistical analysis. Y-yS wrote the first draft of the manuscript. L-fS and Y-lL wrote sections of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.This work was supported by the research grants from Taishan Scholars (No. tsqn202103146), Clinical Research Center of Shandong University (No. 2020SDUCRCC027), and the National Natural Science Foundation of China .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.


Virtual Reality (VR) therapy is popular in treating children with Cerebral Palsy (CP) as a new technology for rehabilitation. Nevertheless, no substantial evidence supporting VR therapy promotion has been developed to date. This study aimed to investigate the effects of VR therapy on balance in children with CP. We conducted a systematic search in PubMed and Web of Science . The systematic review and meta-analysis included all randomized controlled trials that included children with CP. A total of 18 RCT studies were eligible for inclusion in the systematic review, and meta-analysis was performed on 16 of them. Results showed that the VR intervention was beneficial for balance . We concluded that VR therapy interventions for children with CP have positive effects. However, cautious implementation is needed in clinical applications. Cerebral Palsy (CP) is a neurological disorder caused by non-progressive brain injury and developmental defects . The maiMotor skill training or rehabilitation is commonly associated with improvements in balance and walking ability of the lower limbs . In contVirtual Reality (VR) therapy is a recently popular assistive technology in the rehabilitation of children with CP . Its chaReview studies on VR therapy for children with CP showed that VRG therapy interventions could improve the development of gross motor skills, including strength, balance, coordination, and other physical qualities in children with CP , 37, 38.A systematic review and meta-analysis were conducted and implemented following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) . The onlThe following criteria were met for inclusion in the study. (1) Participants were diagnosed with CP and their age was no more than 18 years. CP was defined as permanent impairments in motor and postural development that were often accompanied by insensitivity, cognition, communication, perception, and behavior problems. Participants had limitations in daily activities. (2) VR was used as a therapeutic intervention. VR was defined as a concept that uses real-time interaction with the patient and feeds back their motor patterns or performance knowledge acquired through visual, auditory, proprioceptive, vestibular, or olfactory stimuli. Visual stimuli could be displayed on a monitor, flat-screen, projection screen, or head-mounted device. VR could potentially produce environments with realistic-looking objects, or it could be a game environment. (3) Randomized controlled intervention studies with pre- and post-experimental performance were assessed using a balanced outcome measure. (4) Effects on balance were measured by motor performance scales or test instruments used pre-and post- VR.The exclusion criteria were: (1) case reports, (2) non-peer-reviewed publications, (3) conference abstracts, (4) non-English language publications, (5) VR as an intervention supplement, (6) studies that included patients with comorbidities, and (7) studies that included other interventions that affected VR balance performance.Data and information were collected in the included studies, including age, gender, number of participants, inclusion and exclusion criteria. The following outcomes were recorded for the VR experimental group: type of VR intervention, blinding of the RCT design, and balanced outcome measures. Two authors independently extracted this information from the included articles .The Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of randomized controlled trials (RCTs) to assess the risk of bias , 46. TheOutcome measures on balance were extracted from the included studies and reported. Extracted data from the article included data related to mean change from baseline and Standard Deviation (SD) and sample size for the VR and control groups. The authors were contacted first if exact values cannot be extracted from the article. If contacting the authors was unsuccessful, alternatively, calculations based on the data provided in the article would be considered. When SD of change scores was not available in the study, the formula described in the Cochrane Handbook was used. For this formula, correlation coefficients were extracted from the available literature of the clinical trials used. All outcomes were included if a study used different outcome measures to determine balance. In these studies, the total number of participants was divided by the number of tests used (according to the Cochrane Handbook) to calculate heterogeneity. Random-effects models were used even when heterogeneity was low because of the different clinical trials used in the included articles: heterogeneity only claimed that the results included in the analysis were not statistically heterogeneous and did not consider differences in the use of different clinical trials . StandarA total of 493 articles were retrieved after searching PubMed and WOS databases to remove duplicate data, of which 57 full-text articles were checked for eligibility . The 18 A total of 474 patients were included in the 18 studies . The ageSixteen studies included in the meta-analysis identified PEDro scores to assess methodological quality. Of these studies, fourteen scored ≥6 on the PEDro scale, which denotes good quality. The other two studies scored 5  and 3 5, respectThe applied VR interventions could be categorized into two groups . One groOf the 18 studies that used balance as an outcome measure, five reported static balance . Ledebt For dynamic balance, there were various tests used in 15 articles. Cho et al. , Decavelx2 = 16.77, df = 34, p = 0.99, I2 = 0%). The SMD value was 0.47  supporting the VR intervention , PRT, DBT, and CoP. There were 235 participants in the VR group and 235 participants in the control group. The combined statistics was not heterogeneous .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.