Trapped temporal horn (TTH) is a localized hydrocephalus that can be treated with cerebrospinal fluid diversion. Refined temporal-to-frontal horn shunt (RTFHS) through the parieto-occipital approach is rarely reported in the literature and its effectiveness remains unclear. The aim of the present study is to investigate the efficacy and outcome of RTFHS for treatment of TTH.We consecutively enrolled 10 patients who underwent RTFHS for TTH after surgical resection of peri- or intraventricular tumors from February 2018 to March 2021. Clinical, radiological, and follow-up data were collected and analyzed. The most common underlying pathology was meningioma (n=4), followed by central neurocytoma (n=3), thalamic glioblastoma (n=2), and anaplastic ependymoma (n=1).3 (range 31.7-118.6cm3), respectively. All patients  presented with periventricular brain edema (PVBE), while midline shift was observed in 9 patients . RTFHSs were implanted using valveless shunting catheters. No patients developed acute intracranial hemorrhage or new neurological deficit postoperatively. During the follow-up of 17.2 ± 13.7 months (range 3-39 months), all patients showed clinical and radiological improvement. The mean KPS score at the last follow-up was significantly increased to 88.0 ± 10.3 . RTFHS resulted in significant complete remission in PVBE and midline shift in 8  and 9  patients, respectively. As the postoperative follow-up duration prolonged, the mean TTH volume decreased in a consistent, linear trend (p<0.0001). At last follow-up, the mean TTH volume was significantly reduced to 15.4 ± 11.5 cm3 , resulting in a mean relative reduction of 77.2 ± 13.1% compared with the volume of TTH at onset. Over drainage was not observed during the follow-up. No patient suffered from proximal or distal shunt obstruction or shunt related infection, and the revision rate was 0%.The mean Karnofsky performance scale (KPS) score and TTH volume at onset were 54.0 ± 15.1 (range 40-80) and 71.3 ± 33.2cmRTFHS seems to be safe and effective for the treatment of TTH with favorable outcomes. Advantages of this technique could be technically less complex and invasive, cost-effective, avoidance of various intraperitoneal complications, and maintaining a near-physiological CSF pathway. Trapped temporal horn (TTH) can be a complication after surgery of lesion within or adjacent to the lateral ventricular trigone –3. The oAs a localized hydrocephalus, TTH can be managed with CSF shunting to extracranial compartments, most commonly the peritoneal cavity . HoweverThe freehand technique for frontal catheter insertion is based on fixed anatomical landmarks and does not take individual variation, such as midline shift and distorted ventricle, into consideration. Neuro-navigation has been applied and improved the accuracy of catheter insertion. However, this technique requires more time and resources . A patieThe aim of the present study is to describe the technique of refined temporal-to-frontal horn shunt (RTFHS) through the parieto-occipital approach with assistance of Sina application and report the preliminary experiences on the efficacy and outcome of RTFHS for the treatment of TTH.We retrospectively analyzed the clinical records of 10 consecutive patients who underwent RTFHS for TTH after surgery of peri- or intraventricular tumors between February 2018 and March 2021 at our institution. Medical records and radiological findings were reviewed. The underlying pathology included meningioma in 4 cases, central neurocytoma in 3 cases, thalamic glioblastoma in 2 cases, and anaplastic ependymoma in 1 case. The neurological status was evaluated with Karnofsky performance scale (KPS). CT and/or MRI were employed for diagnosis of TTH preoperatively and to monitor TTH evolution in the following days. The TTH volume index was calculated according to the formula for the volume of a spheroid: 4/3 × π × (length/2) × (width/2) × (height/2). Reduction of the TTH volume, and periventricular brain edema (PVBE) were defined and calculated as reported in the previous study . This stSchematic diagram of RTFHS technique is illustrated in In some cases, the TTH may presents as giant mass . BrieflyP<0.05.The demographics and clinical characteristics were described in terms of means ( ± SD) and frequencies. Fisher’s exact test and Wilcoxon matched-pairs signed ranks test was used to assess the differences of clinical and radiological data between TTH at onset and at last follow-up. The statistical software SPSS 13.0  was used. Probability values were reported as 2 sided, with statistical significance defined as 3 (range 31.7-118.6cm3). The clinical data are summarized in There were 4 male and 6 female with a mean age of 40.0 ± 22.1 years. The mean time interval from tumor resection to TTH onset was 5.2 ± 6.6 months (range 8 days-19 months). Symptoms of intracranial hypertension was the most common presentation (60.0%). The mean KPS score at onset was 54.0 ± 15.1 (range 40-80). Eight TTHs (80.0%) were located in the left hemisphere and 2 (20.0%) in the right. Moderate and severe PVBE were presented in 3 (30.0%) and 7 (70.0%) patients, respectively. Midline shift was observed in 9 cases (90.0%), and the mean distance of midline shift was 6.2 ± 4.1 mm (range 0-11mm). The mean TTH volume at onset was 71.3 ± 33.2cm3 (range 3.3-73.2 cm3), 19.8 ± 14.8cm3 (range 5.6-53.0 cm3), and 15.4 ± 11.5 cm3 (range 5.6-44.1 cm3), respectively , all patients showed clinical and radiological improvement. The mean KPS score at the last follow-up was 88.0 ± 10.3 (range 70-100). All patients demonstrated immediate and further radiographic resolution after RTFHS . Radiologically, RTFHS resulted in a significant complete remission in PVBE (p=0.0007) and midline shift (p=0.0001). In addition, the mean TTH volume at last follow-up was significantly reduced . As the postoperative follow-up duration prolonged, the mean TTH volume decreased in a consistent, linear trend , 4 of which demonstrated a severe degree. Nevertheless, successful penetration of the frontal horn was achieved in all cases and the postoperative imaging confirmed the distal end in position.Another critical stage of RTFHS procedure is the insertion of the distal catheter. In our series, the mean TTH volume at onset was 71.3 ± 33.2cmThe present study included a much larger number of cases treated with TFHS than prior studies. Clinical improvement was achieved immediately after shunt insertion. TTH volume, PVBE, and midline shift were substantially improved at the last follow-up. No patients suffered from proximal or distal shunt obstruction or shunt related infection during the follow-up. Our experience demonstrates that the refined and modified technique can be a safe, effective, and durable CSF diversionary procedure. Further prospective multicenter study with more cases and extended follow-up will be necessary to validate this technical approach.The RTFHS has several advantages over the conventional VPS. First, the shunt system in RTFHS is shorter in length and confined to the skull, which makes the operation technically less complex and invasive and minimizes the risk of mechanical failure and infection. Second, siphoning phenomenon and overdrainage always occur in patients with VPS and have not been eliminated despite with the use of antisiphoning devices –9. RTFHSEl-Shafei et al.  pioneereThis was a retrospective review of a rare series of TTH cases that was treated by RTFHS. Although the morphometric changes including TTH volume, PVBE, and midline shift were evaluated, there were some important CSF hydrodynamic parameters that were not investigated due to the retrospective nature of the study. These hydrodynamic parameters can help to gain more insight into the pathophysiology of non-communicating hydrocephalus patients. In recent studies, 3D fluid-structure interaction modeling was utilized to examine the correlation between CSF hydrodynamic changes and non-communicating hydrocephalus patients’ clinical symptoms before and after shunting , 25. TheRTFHS seems to be safe and effective for the treatment of TTH with favorable outcomes. RTFHS might be a potential alternative to traditional VPS for patient with TTH. Advantages of this technique could be technically less complex and invasive, cost-effective, avoidance of various intraperitoneal complications, and maintaining a natural and near-physiological CSF pathway. Multicenter prospective study with a great number of patients is necessary to validate the potential benefits of this technique so that it can be widely recommended.The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.The studies involving human participants were reviewed and approved by Ethics Committee of Beijing Tiantan Hospital. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.XR, SL, and ZL contributed to conception and design of the study. XR organized the database. XR and ZL performed the statistical analysis. XR and ZL drafted the manuscript. XR and ZL wrote sections of the manuscript. All authors contributed to manuscript revision, read, 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.


To investigate the prevalence and time trends of refractive error (RE) among Chinese children under 18 years old.PubMed, Embase, Web of Science were searched for articles that estimated prevalence of RE in Chinese children. Data of identified eligible studies was extracted by two investigators independently. Pooled prevalence of RE and its 95% confidence interval (95% CI) and the time trends of RE were investigated using Meta-analysis methods.Of the 41 studies covering 1 051 784 subjects, the pooled prevalence of myopia, high myopia, hyperopia and astigmatism in Chinese children was 38.0%  = 35.1%-41.1%), 2.8% (95% CI = 2.3%-3.4%), 5.2% (95% CI = 3.1%-8.6%) and 16.5% (95% CI = 12.3%-21.8%), respectively. Subgroup analysis show that children living in urban were at higher risk of RE. Prevalence of myopia and hyperopia were higher in Northern China compared with Southern China and high myopia and astigmatism were higher in Hong Kong, Macau and Taiwan than in mainland China. Regression analysis showed an upward trend in myopia and hyperopia and a downward trend in high myopia and astigmatism with years.The prevalence of RE is higher in urban areas than in rural for Chinese children. The much higher prevalence of myopia and astigmatism in China compared with foreign countries indicates the important role played by environment and genetic factors. Considering the large magnitude of refractive errors, much more attention should still be paid to RE prevention and treatment strategy development in China. Refractive error (RE) has been one of the most common eye disorders among children and adolescents and one of the major public health concerns in the world. It has been reported that 42% of visual impairments are caused by RE globally . RE haveIn East Asia, the high prevalence of RE has been a major public health concern. For urban areas of these countries, about 80% of the adolescents in high school are myopic, while 10%-20% of them suffer from high myopia . Also, iConsidering the impact of RE and its high prevalence, it is undeniable that there is great value in further understanding the epidemiology of RE for the purposes of policy making. Particularly, policy of myopia prevention and control has been a hotspot in the field of public health since the rapid rise of prevalence of myopia in China. Although numerous population-based or school-based studies and meta-analysis have been performed to evaluate the prevalence of RE in China, most of them focus on myopia and high myopia -13, whicConsidering an overall estimate of the magnitude and its time trends of RE is important for RE prevent and control, we performed this meta-analysis and comprehensive systematic review to evaluate the prevalence of refractive errors, time trends, and its sub-classifications among children in China, which might provide useful information for appropriate preventive strategies to reduce the disease burden caused by SE in China and beyond.The protocol of the meta-analysis was registered in PROSPERO website  with a registration number of CRD42020197708. In order to extract articles providing prevalence data of refractive errors in Chinese children, bibliographic databases including PubMed, EMBASE, and Web of Science were searched with different combinations of words includingPopulation: “China”, “Chinese”, “Taiwan”, “Macau”, “Macao”, “Hong Kong”Outcome: “refractive errors”, “myopia”, “astigmatism”, “hyperopia”Study design: “Prevalence”, “Epidemiology”, “epidemiology”, “prevalence”, “incidence”The search was conducted by two investigators  independently with the final search date of July 28, 2019.After the search, 4240 articles were identified. 1641 duplicate articles were removed. The selection was conducted by two investigators independently with the following criteria:The inclusion criteria were as follows: 1) school-based studies or population-based studies with clearly defined sampling strategies; 2) studies reporting the prevalence of refractive errors in Chinese children younger than 18 years old; 3) studies with a clear definition of refractive errors; 4) sample size of at least 1000 subjects. Studies with sample size less than 1000 were excluded because it’s age-defined subgroups would be too small for a reliable assessment of the prevalence of refractive errors.The exclusion criteria were as follows: 1) hospital-based or clinical-based surveys; 2) conducted only in a single school; 3) using visual acuity as the measurement for refractive errors; 4) missing or incomplete data; 5) obvious limitations in their statistical analysis or design; 6) different studies based on the same population without providing additional information.The searches were limited to English language literature only. After the selection procedure, 41 articles that met the inclusion criteria were carefully reviewed by two investigators . The extracted data of these articles are listed as follows:Characteristics of the study: author, study year, design of study, refraction with or without mydriatics.Characteristics of the studied population: sample size, age range, district and region  of the sample, percentage of female subjects.Prevalence data: definition and prevalence of refractive errors.P < 0.05 (2-tailed). Funnel plots were also performed for publication bias when more than 10 studies were involved in the meta-analysis. Sensitivity analysis of studies included in myopia, high myopia, hyperopia, astigmatism were conducted. Time trends of refractive errors were also investigated by meta regression. This meta-analysis was performed with the Comprehensive Meta-Analysis Software V.2 .Pooled prevalence of refractive error and its 95% confidence interval (95% CI) was estimated. Subgroup analyses were conducted for potential difference in region and study year. The I-square test was performed to estimate the heterogeneity of the included studies . When the I-square test suggested a high degree of heterogeneity, a random effect model was used, otherwise a fixed effect model was used. To acces, Panel A, the pooled prevalence of myopia was 38.0% (95% CI = 35.1%-41.1%). Urban children had a significantly higher prevalence of myopia than rural children: 51.2% (95% CI = 50.8%-51.5%) vs 27.1% (95% CI = 26.7%-27.5%); P < 0.001. Additionally, pooled prevalence in HMT and Northern China were similar: 53.0% (95% CI = 52.6-53.4%) vs 55.1% (95% CI = 54.9%-55.3%), while Southern China hadhas the lowest prevalence: 31.4% (95% CI = 31.0%-31.7%), P < 0.001. The subgroup analysis of study year shows that there was a higher prevalence before the year 2000: 49.3% (95% CI = 37.9%-60.7%). However, as the regression analysis shows .As is shown in , Panel B. The pooled prevalence of high myopia was 2.8% (95% CI = 2.3%-3.4%). There was a higher prevalence of high myopia in urban areas vs rural areas: 3.0% (95% CI = 2.3%-3.8%) vs 0.9% (95% CI = 0.3%-2.9%); P < 0.001. For populations in different districts, HMT and Northern China had similar pooled prevalence: 4.9% (95% CI = 3.5%-6.9%) vs 4.6% (95% CI = 3.6%-5.7%), and Southern China still had the highest pooled prevalence: 0.5% (95% CI = 0.3%-0.8%), P < 0.001. Meta regression .Result of the meta-analysis of high myopia is presented in , Panel C, pooled prevalence of hyperopia was 5.2% (95% CI = 3.1%-8.6%). Prevalence of hyperopia was higher in urban children than in rural children: 4.0% (95% CI = 1.3%-11.4%) vs 5.4% (95% CI = 3.4%-8.4%); P < 0.001. However, prevalence of hyperopia in HMT was lowest, while Northern China had the highest prevalence: 5.3% (95% CI = 4.9%-5.8%) vs 27.8% (95% CI = 27.1%-28.6%); P < 0.001. As for the subgroup analysis of study year, prevalence of hyperopia after the year 2010 was highest while prior to the year 2000 was lowest: 5.9% (95% CI = 3.4%-9.9%) vs 3.2% (95% CI = 2.1%-4.9%); P < 0.001. Result of the meta regression .As shown in and P < 0.001. Prevalence of astigmatism in HMT  was highest, while prevalence in Southern China was lowest ; P < 0.001. Before the year 2000 the prevalence of astigmatism was highest and prevalence was lowest in the years 2000-2010  vs 47.6% (95% CI = 5.2%-16.7%); P < 0.001. A decreasing trend was detected in the meta regression analysis, which is shown in Figure S4 in the P < 0.01).P > 0.05). We have also conducted the sensitivity analysis and the pooled prevalence RE did not change significantly compared with the initial results after removing each study sequentially, suggesting good homogeneity of the included studies.According to the result of the Begg’s and Egger’s test, there was no publication bias detected for the prevalence of myopia, hyperopia and astigmatism  and predicted that the estimated prevalence of myopia in 2050 was 84% . This miComparing the prevalence of myopia in different countries, we found that prevalence of myopia and high myopia in Chinese children is significantly higher than in many other countries. For example, the prevalence of myopia ranges from 6.1% in Morocco , 4.0% inIn terms of hyperopia, as the first meta-analysis reporting prevalence of hyperopia in Chinese Children, our results show a higher prevalence was detected in urban compared to rural areas which is inconsistent with the study performed in India which showed children in rural areas were more likely to develop hyperopia than those in urban areas . In our When comparing the prevalence of hyperopia with other countries and regions, prevalence of hyperopia is relatively low in China which is similar to other east Asian countries. For example, the prevalence of hyperopia is 1.5% in Singapore and 6.2% in Korea ,67. In cThe prevalence of astigmatism in Chinese children is 16.5% and highest prevalence was seen in HMT (35.7%), which is higher than many countries. For example, prevalence was only 5.4% in India, 6.7% in Australia and 9% in Laos ,62,71. AThis study has several limitations. First, few studies were prior to the 2000 or in remote provinces which will affect the precision of the results to a certain extent. Second, not all the studies used the same definition of RE which might influence the result in some extent. Third, out of 40 studies, 9 of them did not perform cycloplegia for refractometry which might also influence the result. Nevertheless, to the best of our knowledge, this is the first meta-analysis to report the overall prevalence and time trend analysis of refractive errors and its sub-classifications in Chinese children. Additionally, this article includes numerous studies throughout China, covering a large population with a wide geographical distribution.The pooled prevalence of myopia, high myopia, hyperopia, astigmatism in Chinese children are 38.0%, 2.8%, 5.2%, 16.5%, respectively. Urban children are more vulnerable to RE  than rural children. Children living in HMT have a higher prevalence of myopia, high myopia and astigmatism than children in mainland China. There is an increasing trend for prevalence of myopia and hyperopia while there is a decreasing trend for prevalence of high myopia and astigmatism in Chinese children. Considering the large magnitude of refractive errors, more attention should be paid to RE prevention and treatment strategy development in China.


Primary hyperparathyroidism (PHPT) is a disease that is diagnosed more frequently and generally in the asymptomatic period, with widely available biochemical tests. Evidence suggesting an association between PHPT and malignancy risk is increasing. Clarification of this association will be useful in PHPT for malignancy screening and management of patients with PHPT. In this study, we aimed to investigate the frequency of cancer in PHPT patients.A total of 775 PHPT patients were included in the retrospective study. Demographic, clinical and laboratory data of the patients were evaluated retrospectively.Malignancy was detected in 128 (16.50%) of 775 PHPT patients . The mean age at diagnosis of PHPT was 57.99 ± 10.86 years, and the mean age at diagnosis of malignancy was 57.46 ± 11.17 years. Of the 128 patients with malignancy, 53 (41.40%) were diagnosed in the same year as PHPT. In terms of malignancy types, 51 (6.50%) of 775 PHPT patients had thyroid cancer. Thyroid cancer was followed by breast cancer (2.30%) and stomach cancer (1%) in order of frequency.We think that PHPT patients should be examined more carefully in terms of cancer risk, especially thyroid cancer. More comprehensive studies are needed to clarify the relationship between PHPT and cancer. Primary hyperparathyroidism (PHPT) is a disease characterized by hypercalcaemia and elevated or inappropriately normal serum level of parathyroid hormone (PTH) due to parathyroid adenoma, hyperplasia or rarely cancer. As biochemical tests are widely available, PHPT has become a disease that is diagnosed more frequently and generally in the asymptomatic period today. PHPT is a relatively common endocrine disease with an incidence of up to 1 in 1000 patients. PHPT can be seen at all ages, but it is most common in the sixth decade of life; women are affected three times more often than men [1–2]. Half of all patients with PHPT are postmenopausal women [3]. Its treatment requires surgical resection of the related parathyroid gland or glands.Increasing incidence of PHPT and good prognosis have raised concerns about many different types of cancer that occur during the follow-up of these patients. In addition, PHPT can occur in patients who are followed for any cancer. There are studies reporting that many types of cancer such as breast, kidney, colon, skin, pancreas, lung, hematopoietic , pituitary, thymus, adrenal and thyroid are more common in patients with PHPT than in the general population [4–7]. In terms of the frequency of individual cancer types in PHPT patients, it is seen that there are more studies showing that the frequency of thyroid cancer has increased in those patients [8–10].Evidence suggesting an association between PHPT and malignancy risk is increasing. The clarification of this association will provide useful information for malignancy screening in patients with PHPT and long-term management of those patients. In this study, we aimed to investigate the frequency of cancer in PHPT patients.A total of 775 patients who were followed-up with the diagnosis of PHPT between 2006 and 2019 were included in this retrospective study. Necmettin Erbakan University Meram Medical School Ethics Committee approved the study. PHPT complications such as osteoporosis and nephrolithiasis, the demographic, clinical, laboratory, radiological and pathological data of the patients were documented from the hospital’s electronic registry. The presence of an accompanying malignancy, ages at the time of diagnosis of PHPT and malignancy were questioned.Statistical analyses were performed using the SPSS 22.0  program. Continuous variables were given as mean ± standard deviation if the distribution was normal and as median (minimum-maximum) if the distribution was not normal. In the comparison of independent group differences, the significance test of the difference between the two means (independent samples t test) was used when the parametric test assumptions are provided. The Mann–Whitney U test was used to compare the independent group differences when the parametric test assumptions were not provided. For differences, p < 0.05 value was considered statistically significant.The data of 775 patients with PHPT were analyzed in this study. 625 (80.6%) of the 775 patients were female, and 150 (19.4%) patients were male. 128 (16.5%) of 775 PHPT patients were found to have a diagnosis of malignancy. The mean age of the study population was 57.99 ± 10.86 years at the time of the diagnosis of the PHPT and 57.46 ± 11.17 years at the time of the diagnosis of the accompanying malignancy. The median follow-up was 5 (1–13) years for PHPT and 5 (1–14) years for accompanying malignancy.parathyroid adenomas were located on the right inferior in 46.1% of patients, left inferior in 41.0% of patients, right superior in 5.0% of patients, left superior in 4.8% of patients and medistinal in 1.5% of patients. Laboratory evaluation showed that the median level of serum calcium (Ca) was 11.20 (10.00–15.80) mg/dL, albumin-corrected Ca was 11.13 (9.36–16.80) mg/dL, PTH was 173 (68 –1604) pg/mL, albumin was 4.3 (2.5–5.5) g/dL, phosphorus (P) was 2.7 (0.9–6.2) mg/dL. The median 24-h urinary Ca excretion was 310 (100–1568) mg/day. In females, serum Ca was 11.00 (10.00–15.80) mg/dL, albumin-corrected Ca was 11.05 (10.00–16.80) mg/dL, P was 2.72 (1.10V 5.60) mg/dL, albumin was 4.3 (3.2–5.2) g/dL and 24-h urinary Ca excretion was 331 (100–1568) mg/day (reference range < 250 mg/day), while, in males, serum Ca was 11.61 (10.00–15.40) mg/dL, albumin-corrected Ca was 11.44 (10.00–15.77) mg/dL, P was 2.50 (0.90–6.20) mg/dL, albumin was 4.2 (2.5–5.5) g/dL and 24-hour urinary Ca excretion was 409 (101–956) mg/day (reference range < 300 mg/day). According to the dual-energy X-ray absorptiometry (DEXA) and urinary ultrasonography results, 32.9% of patients had osteoporosis and 17.1% had nephrolithiasis (Table 1). Frequency of nephrolithiasis was significantly higher in men than in women . There was no difference between men and women in terms of the frequency of osteoporosis .Parathyroid adenoma could be localized in 74.5% (577/775) of patients and based on ultrasonography, the A total of 128 (16.5%) of 775 PHPT patients were found to have a diagnosis of malignancy. The frequency of malignancy in PHPT patients was 29/150 (19.3%) in men and 99/625 (15.8%) in women, but this difference did not reach statistical significance (p = 0.327). Of the 128 patients with malignancy, 53 (41.4%) were diagnosed in the same year as PHPT, 33 (25.7%) were diagnosed before PHPT, and 42 (32.8%) after PHPT. In terms of malignancy types, 51 (6.5%) of 775 PHPT patients had thyroid cancer , and 27 of these 51 thyroid cancer patients had the diagnosis of thyroid cancer and PHPT simultaneously .Of the 775 PHPT patients, 273 had thyroid nodules. The mean number of nodules was 1.96 ± 0.95, and 242 of them were solid and 31 of them were cystic nodules. Of the nodules, 31 were anechoic, 96 were hypoechoic, 127 were isoechoic, and 19 were hyperechoic. Mean nodule size was found as 12.44 ± 8.15 mm.Thyroid surgery was performed in 90 patients concurrently with PHPT surgery, 7 of these 90 patients were subjected to thyroid surgery due to preoperative malignant fine-needle aspiration biopsy results, and 83 due to multinodular goiter. Postoperative final thyroidectomy pathology results were benign in 65 patients and malignant in 25 patients.There was no significant difference between those with and without malignancy in PHPT patients in terms of age, sex, follow-up time and biochemical parameters such as Ca, P, PTH, vitamin D, creatinine and urinary Ca level. The age at the time of diagnosis of parathyroid adenoma was higher in those with malignancy than those without malignancy (p = 0.019) (Table 3).According to the results of our study, 128 (16.5%) of 775 PHPT patients were found to have an accompanying malignancy. The most common accompanying malignancies were determined as thyroid cancer, breast cancer and stomach cancer (51 (6.5%), 18 (2.3%) and 8 (1.0%) of patients, respectively).Several studies have shown that PHPT patients have an increased risk of malignancy that persists after surgery. The increased risk may be associated with hypercalcemia itself. High calcium levels may increase the risk of cancer by inducing mitotic activity. There are also some experimental studies suggesting that PTH has a tumor-promoting effect and an apoptosis-inhibiting effect. However, the long-term persistence of the postoperative cancer risk has reduced the likelihood of biochemical irregularities that contribute to the risk of cancer and focused on other likely mechanisms. Vitamin D inhibits angiogenesis and invasiveness, induces apoptosis, cell cycle arrest and differentiation, thus, exhibiting an anti-tumor effect, and vitamin D receptors are present in many different cells. Defects in the vitamin D receptor alleles cause a genetic predisposition. This genetic predisposition may cause impairment in the regulation of the functions of the parathyroid glands, as well as impaired apoptosis and an increase in preneoplastic lesions .According to the GLOBOCAN 2018 data, in both sexes combined, lung cancer is the most commonly diagnosed cancer , closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) [12]. In 2018, the incidence of all cancers in our country was determined as 225.1 per 100.000 persons and lung cancer (16.5%), breast cancer (10.6%), colorectal cancer (9.5%), prostate cancer (8.2%), thyroid cancer (6.2%) and stomach cancer (5.0%) constitute the first 6 types of cancer in order of frequency [12]. In our study, the rate of malignancy in PHPT patients was found to be 16.5%, and it was found to be at a higher frequency than the general population. In addition, unlike the general population, thyroid cancer was found to be the most common accompanying malignancy in PHPT patients.A study including 9782 operated patients from Sweden showed an increased risk of cancer in both sexes, with risk persisting for more than 15 years after surgical correction of PHPT. The authors reported that breast cancer accounts for a quarter of all cancer cases in women, with an increased risk of colon, kidney, and squamous cell cancer in both sexes. An interesting result found in that study is that the risk of endocrine and pancreatic cancer is increased in the small subgroup operated before the age of 40 [5]. In our study, breast cancer was seen in 2.3% of PHPT patients and ranked second after thyroid cancer among cancers cases seen in PHPT patients.In a study involving 3039 PHPT patients, Ghosh et al. found an increased incidence of cancer cases in patients who were conservatively managed or surgically treated, and reported that the most common types of cancer were colon, breast, lung and skin (non-melanoma) cancers. The authors also reported that surgery delays the occurrence of cancer but does not reduce it [7]. In our study, both surgically and conservatively managed patients were included, and separate evaluation has not been made for those who underwent surgical treatment and were followed up conservatively. However, in our study, unlike Ghosh et al., the most common cancers were those of thyroid, breast and stomach.papillary thyroid cancer) [13]. In a similar study, Preda et al. reported the incidence of thyroid cancer as 13.6% in PHPT patients who underwent surgery [21]. In our study, the frequency of thyroid cancer in PHPT patients was found to be 6.5%, but, unlike those studies, we did not separately evaluate PHPT patients who underwent surgical treatment.In the literature, the prevalence of thyroid carcinoma with concomitant PHPT ranges from 1% to 36 [13–20]. In their study investigating the prevalence of thyroid disease and thyroid malignancy in patients who underwent surgical treatment for PHPT, Çuhaci et al. found the thyroid malignancy prevalence as 20.8% (all patients with malignant disease had Previous studies have investigated several predisposing factors for papillary thyroid cancer in PHPT patients, such as the tumor promoting effect of PTH [22], the goitrogenic effect and increased mitotic activity induced by hypercalcemia  and neck irradiation . A presumed role for PTH excess in triggering the onset of papillary thyroid cancer remains controversial [26]. In the study of Preda et al., although PTH levels were much higher in patients with secondary hyperparathyroidism, the similar incidence of papillary thyroid cancer in patients with secondary hyperparathyroidism and PHPT is contrary to the opinion that high PTH level may trigger papillary thyroid cancer [21]. Pickard et al. found that cancer risk in patients with secondary hyperparathyroidism was insignificant, and, in the light of this data, they suggested that PTH itself is not the cause of malignancies [27].The limitations of our study are its small sample size, single center and retrospective design.Our study confirms the earlier findings of a connection between PHPT and increased risk of malignancy. It is not clear whether this increased risk is due to genetic predisposition to tumor development or whether it is a physiological associative effect, intrinsic or environmental. For all these reasons, PHPT patients should be examined and monitored more carefully for all cancers, especially thyroid cancer. More comprehensive studies are needed to clarify the relationship between PHPT and cancer.Informed consent was obtained from all participants. Ethics committee approval was obtained from Necmettin Erbakan University Meram Medical Faculty Ethics Committee for the study.


Background: Precisely predicting coronary artery aneurysms (CAAs) remains a clinical challenge. We aimed to investigate whether coronary dimensions adjusted for body surface area (Z scores) on baseline echocardiography and clinical variables before primary treatment could predict the presence of late CAAs.Methods: We conducted a retrospective study including children hospitalized for Kawasaki disease and received intravenous immunoglobulin within 10 days of illness. We defined late CAAs as a maximum Z score (Zmax) ≥2.5 of the left main, right, or left anterior descending coronary artery at 11–60 days of illness. Associations between late CAAs and clinical parameters and baseline maximum Z scores were analyzed.Results: Among the 314 included children, 31 (9.9%) had late CAAs. Male, higher C-reactive protein, and higher baseline Zmax were risk factors of late CAAs. Late CAAs were significantly associated with baseline Zmax ≥2.0 vs. <2.0 . The odds ratio for late CAAs among the patients with baseline Zmax ≥2.0 vs. <2.0 was 18.5 . The sensitivity, specificity, positive predictive value, and negative predictive value of baseline Zmax ≥2.0 for the presence of later CAAs were 80.6, 81.6, 32.5, and 97.5%, respectively.Conclusions: Findings from this study suggest that Zmax ≥2.0 of coronary arteries on baseline echocardiography may be used to predict children at a high risk of late CAAs and allow for targeted early intensification therapy. Kawasaki disease (KD) is an acute vasculitis that mainly affects infants and young children, with Taiwan having the third-highest incidence  worldwide –7. EarlyRisk factors for CAAs include male sex , IVIG trWe retrospectively reviewed charts of all children (aged 0–18 years) diagnosed with KD and administered IVIG (2 g/kg as a single infusion) at MacKay Children's Hospital from January 1, 2012, through December 31, 2018. The exclusion criteria were: (1) not the first episode of KD (recurrent KD); (2) no or unknown IVIG treatment; (3) delayed IVIG treatment (>10 days after fever onset); (4) no baseline echocardiography data (either before or within 2 days of first IVIG administration); (5) no available follow-up echocardiography data during 11–60 days after illness onset; (6) coexisting congenital heart disease ; (7) first laboratory studies obtained ≥1 day after IVIG administration; (8) insufficient laboratory data to calculate established risk scores. This study was approved by the MacKay Memorial Hospital Institutional Review Board (18MMHIS183e).Data on demographic characteristics, presenting symptoms, physical examination findings, laboratory values, echocardiographic data, and treatment were recorded. Patients were classified as complete KD if they had fever plus the presence of ≥4 of the 5 principal clinical features; those who had fever plus <4 clinical criteria with compatible laboratory or echocardiographic findings were classified as incomplete  KD as per the American Heart Association (AHA) definition . The day2 or Fisher's exact test for categorical variables and Student t or Mann-Whitney test for continuous variables. Crude odds ratios for late CAAs among children with clinical and laboratory variables were estimated using univariate analysis. Risk factors identified by univariate analysis were applied for multivariate analysis, the logistic regression with a stepwise regression procedure. A receiver operating characteristic (ROC) curve was generated to identify the predictive validity of each parameter that was found to be significant by multivariate analysis. Youden J statistics were used to determine the most discriminating cutoff value. Sensitivity, specificity, and predictive values of the targeted parameter for late CAAs were calculated. Proportions of children with late CAAs were further categorized into five groups according to baseline Zmax as follows: <1.5, ≥1.5 to <2.0, ≥2.0 to <2.5, ≥2.5 to <3.0, and ≥3.0. A quadratic model was used to estimate the rate of late CAAs in each category based on the baseline Z scores. All P values were based on 2-sided tests and were considered statistically significant at <0.05. All statistical analyses were conducted using SPSS version 21.0 .Descriptive statistics were used for demographic, clinical, and echocardiographic data. Continuous variables were described as mean (standard deviation) and categorical variables as numbers and percentages. Data were compared using χP < 0.001). The median time between the onset of fever and IVIG administration was 6 days (IQR: 5–7 days). Twenty-one patients (6.7%) did not respond to the first dose of IVIG. Among the patients with IVIG resistance, 15 (4.8%) received the second dose of IVIG, 2 (0.6%) received corticosteroids as the second-line treatment, and 3 (1%) received a combination of a second dose of IVIG and corticosteroids.A total of 314 patients with KD were enrolled, of whom 178 (56.7%) were male. Overall, 109 (34.7%) patients received a diagnosis before 1 year of age, 197 (62.7%) between 1 and 5 years of age, and 8 (2.5%) at 5 years of age or older. Thirty-nine (12.4%) patients were classified as having incomplete  KD. Thirty (9.5%) of incomplete  KD patients had three clinical criteria, and night (2.9%) had less than two clinical criteria for KD. Patients with incomplete  KD were younger than those with complete KD  and doses (mg/kg/day) of acetylsalicylic acid administration , proportions of combination primary therapy , and days of baseline echocardiograms (median [IQR]: 6 (P = 0.74). The median time from the initial treatment to second/third echocardiography was 15 (IQR: 11–22) days/50 (IQR: 42–80) days.Overall, 31 patients (9.9%) had the presence of CAAs at 11–60 days of illness. Patients with or without the presence of late CAAs had no differences in days from illness onset to IVIG treatment (median [IQR]: 6 –8 vs. 6 P = 0.04). The Zmax of IVIG non-response patients ranged from 2.9 to 6.1 at 11–60 days after illness onset. All the five IVIG-resistant cases with late CAAs received a second dose of IVIG, and the two received additional corticosteroids as the rescue therapy had Zmax < 3.0. We did not put IVIG resistance into multivariate analysis because it cannot be recognized before primary treatment.The clinical variables identified by univariate analysis to be significant predictors of late CAAs were as follows: male gender, CRP, maximum Z score on baseline echocardiography, and IVIG resistance . PatientP = 0.14) for male gender, OR = 1.04  for CRP, and OR = 4.54  for baseline maximum Z score. Baseline maximum Z score was identified as the sole significant variable at the time of diagnosis that distinguished those who would have the presence of late CAAs from those who would not have at 11–60 days of illness. ROC curve was performed to determine the baseline Zmax that may predict the presence of late CAAs. The cutoff value of baseline Zmax assessed by Youden J statistics was 1.96. We selected a baseline Z score of ≥2.0 as the cutoff value to predict late CAAs. Baseline Zmax ≥2.0 was significantly associated with late CAAs compared with baseline Zmax <2.0 .The other three variables were included in the multivariate logistic regression analysis with the following results: odds ratio (OR) = 2.33 .P = 0.03) at 11–60 days after illness onset. Amongst the 77 patients with baseline Zmax ≥2.0, 34 were <1 year and 43 were between 1–5 years. For patients with baseline Zmax ≥2.0, there was no statistical difference between the two age groups for rates of late CAAs .In baseline echocardiography, 170 (54.1%), 67 (21.3%), 28 (8.9%), 22 (7.0%) and 27 (8.6%) patients had a baseline Zmax of <1.5, 1.5 to <2.0, 2.0 to <2.5, 2.5 to <3.0, and ≥3.0, respectively. The rates of late CAAs in each group, based on maximum baseline Z scores, were revealed in P = 0.99). All cases with baseline Zmax <2.0 who later had CAAs developed small aneurysms at 11–60 days after illness onset. In the group with baseline Zmax ≥2.0, two cases developed medium aneurysms, and one had a giant aneurysm with a dimension of 10.1 mm in the RCA.Comparisons of late CAAs between the patients with baseline Zmax <2.0 and ≥2.0 are summarized in P = 0.39).Among the 31 patients with late CAAs at 11–60 days of illness onset, 27 had their coronary arteries regress to normal Z scores 2–12 months after illness onset, and two regressed in the 1–2 years follow-up period. Two patients (0.6%) had aneurysms that persisted until the last follow-up . For the patients who recovered from late CAAs, those with baseline Zmax ≥2.0 took a longer average time to return to a normal coronary artery dimension on echocardiography than those with baseline Zmax <2.0 (3.4 ± 2.3 vs. 2.4 ± 1.5 months; In this analysis of echocardiography using body surface area-adjusted coronary artery dimensions in children with KD, the rate of late CAAs increased with each higher category of baseline maximum Z score. The agreement between baseline Zmax ≥2.0 on baseline echocardiography and the presence of late CAAs at 11–60 days of illness was strong, as Zmax ≥2.0 on baseline echocardiography increased the risk of CAAs at 11–60 days of illness by a factor of 18.5. More than four-fifths of the children who had CAAs at 11–60 days of illness were identified in baseline echocardiography, suggesting that these children at risk of developing CAAs may have been identified early and received tailored primary treatment using this approach.As reported in previous studies, the patients who developed coronary aneurysms had higher maximum Z scores from the initial assessment. Liu et al. reported that a maximal Z score ≥2.5 during the acute KD phase predicted persistent or progressive coronary aneurysms at one month after KD onset in more than two-thirds of their patients . In addiOne-third of our patients with baseline Zmax ≥2.0 of the LMCA, RCA, or LAD developed CAAs during 11–60 days of illness. A recent study in a North American center showed that baseline Zmax ≥2.0 of the RCA or LAD was associated with later CAAs at 4–8 weeks after illness onset . On the Z scores of the LMCA need to be interpreted with caution due to the more common anatomic variations in this artery . It can Sensitivity and specificity of baseline Zmax were good for the prediction of the later development of CAAs in our patients. However, it had a low positive predictive value, which may be due to the regression of coronary arteries from a higher to normal Z score after IVIG treatment. Conversely, the negative predictive value was 97 %, as patients with baseline Zmax <2.0 were less likely to develop CAAs at 11–60 days after illness onset.Most children with KD have good clinical outcomes after treatment with a single dose of IVIG in the first 10 days of illness; however, around 10% of children with KD still had CAAs in the first 60 days of illness in our study. The children with a baseline Zmax ≥ 2.0 developed larger CAAs in the subacute and convalescent stages. Their affected coronary arteries took more time to return to normal dimensions compared to the children with a baseline Zmax < 2.0, although the difference was not statistically significant. Although most CAAs may remodel to a normal lumen diameter over time, the appearance of aneurysm regression on echocardiography can be a result of myofibroblast cell proliferation or layered thrombus that may be followed by persistent abnormal vascular wall morphology and vascular dysfunction at the site of the regressed coronary aneurysm , 33. MorThis study has several limitations. First, the study is limited by its retrospective design. Considering that late CAAs may spontaneously regress over time, a prospective study with more frequently repeated echocardiograms may better detect the occurrence of late CAAs. We may have missed some less severe cases because follow-up echocardiography for patients without baseline CAAs tends to be postponed, and only patients with outcome data from echocardiograms during the study period were included. In addition, most of the patients with IVIG resistance received additional therapy, which would have biased our study towards less positive results by improving coronary artery outcomes at 11–60 days of illness. Moreover, the relatively small number of patients with late CAAs restricted our ability to reach some comparative conclusions between those with baseline Zmax < 2.0 and ≥2.0.Our findings demonstrate that the maximum Z score of coronary arteries on baseline echocardiography may be a predictor of the presence of CAAs at 11–60 days of illness. Z score of coronary arteries may therefore be an imaging biomarker to promptly identify patients at risk of developing CAAs to allow for tailored primary therapy to prevent the development and progression of CAAs. Further studies are needed to validate our findings in other populations.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.C-YH and HC conceptualized and design the study. C-YH wrote the first draft of the manuscript. N-CC, F-YH, and Y-CC collected and organized the database. All authors critically reviewed, revised the manuscript, and agreed to the published version of the manuscript. 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.


The validation of inferior vena cava (IVC) respiratory variation for predicting volume responsiveness is still under debate, especially in spontaneously breathing patients. The present study aims to verify the effectiveness and accuracy of IVC variability for volume assessment in the patients after abdominal surgery under artificially or spontaneously breathing.A total of fifty-six patients after abdominal surgeries in the anesthesia intensive care unit ward were included. All patients received ultrasonographic examination before and after the fluid challenge of 5 ml/kg crystalloid within 15 min. The same measurements were performed when the patients were extubated. The IVC diameter, blood flow velocity–time integral of the left ventricular outflow tract, and cardiac output (CO) were recorded. Responders were defined as an increment in CO of 15% or more from baseline.There were 33 (58.9%) mechanically ventilated patients and 22 (39.3%) spontaneously breathing patients responding to fluid resuscitation, respectively. The area under the curve was 0.80 (95% CI: 0.68–0.90) for the IVC dimeter variation (cIVC1) in mechanically ventilated patients, 0.87 (95% CI: 0.75–0.94) for the collapsibility of IVC (cIVC2), and 0.85 (95% CI: 0.73–0.93) for the minimum IVC diameter (IVCmin) in spontaneously breathing patients. The optimal cutoff value was 15.32% for cIVC1, 30.25% for cIVC2, and 1.14 cm for IVCmin. Furthermore, the gray zone for cIVC2 was 30.72 to 38.32% and included 23.2% of spontaneously breathing patients, while 17.01 to 25.93% for cIVC1 comprising 44.6% of mechanically ventilated patients. Multivariable logistic regression analysis indicated that cIVC was an independent predictor of volume assessment for patients after surgery irrespective of breathing modes.IVC respiratory variation is validated in predicting patients' volume responsiveness after abdominal surgery irrespective of the respiratory modes. However, cIVC or IVCmin in spontaneously breathing patients was superior to cIVC in mechanically ventilated patients in terms of clinical utility, with few subjects in the gray zone for the volume responsiveness appraisal.ChiCTR-INR-17013093. Initial registration date was 24/10/2017.The online version contains supplementary material available at 10.1186/s12871-022-01598-5. The purpose of fluid therapy is to attain the maximal increase in cardiac output (CO) after fluid replenishment . HoweverCurrently, conventional static indicators comprising central venous pressure (CVP), urine output, et al., are poorly associated with volume status and cannot accurately predict patients' volume responsiveness . In addiTherefore, the present study aimed to evaluate the validity and accuracy of respiratory variation in IVC diameter to predict the volume responsiveness in patients after surgery under artificial or spontaneous breathing mode and provided a new train of thought for fluid management.This study was approved by the ethics committee of Nanjing Drum Tower Hospital with approval number [No.2017–122-02]. The patient provided written consent. All methods were carried out in accordance with Declaration of Helsinki.2. The patients with an irregular rhythm, cardiopulmonary dysfunction, liver, kidney function failure, incomplete clinical data, difficulty in delineating the anatomic structure due to obscure images of IVC and heart by transthoracic ultrasound examination were excluded.From May 2018 to December 2018, a total of 60 consecutive patients scheduled for elective major abdominal operation in the anesthesia ICU (AICU) were recruited in this study. The inclusion criteria comprise the patients aged between 20 to 70-year-old, with American Society of Anesthesiologists (ASA) physical status classification I to III, body mass index (BMI) with the range of 20–26 kg/m2O before IVC ultrasound assessment. The phased-array ultrasound probe (8–10 Hz) was placed at the intersection between the right mid-axillary line and the fifth to seventh intercostal space of patients at a supine position with the probe marker towards cephalad. The maximum IVC diameter (IVCmax) on inspiration and IVCmin on expiration were measured under M-mode modality respectively. The diameter variation of IVC (cIVC1) was calculated using the equation: cIVC1 = (IVCmax-IVCmin)/IVCmax × 100%. Thereafter, the left ventricular outflow tract (LVOT) acquisition in a parasternal long-axis view and its bloodstream via pulse-doppler from five-chamber apical view yields LVOT velocity time integral (VTI) and CO , mean arterial pressure (MAP), CVP, cIVC1 or cIVC2, the difference of the maximum and minimum IVC diameter (ΔIVC), VTI, cardiac index (CI) and CO of patients were collected at the following time-points: 5 min stabilization after patient entering AICU under mechanical ventilation (T1), following the first fluid challenge test (T2), 5 min stabilization after extubation under spontaneously breathing (T3) and following the second fluid challenge test (T4). The overall perioperative loss and supplementary volume in patients were recorded.The results of our pilot study of 20 patients showed that the AUC of cIVC1 predicted volume responsiveness under mechanical ventilation was 0.74, and the AUC of cIVC2 under spontaneous breathing was 0.8. Therefore, we choose a rather low value of 0.74 to calculate the sample size. The result showed that at least 54 patients were required to detect the difference of 0.24 between the AUC of cIVC1 (0.74) and the null hypothesis (0.5), with a power of 0.9 and a two-tailed type I error of 0.05, assuming the volume responsiveness incidence of 50% in patients after abdominal surgery. To allow for a possible 10% dropout rate, a sample size of 60 was used.According to the Shapiro–Wilk test results, continuous data were presented as mean ± standard deviation or median (25 to 75% interquartile range) to test the normality of data distribution. Baseline hemodynamic parameters between the two groups were assessed using an independent Student’s t-test or Man-Whitney U test. The paired Student’s t-test or nonparametric Wilcoxon test was used to comparing the hemodynamic and echocardiographic indicators before and after the fluid challenge. Categorical data were compared using the χ2 test. According to the normality of two variables, the Pearson or Spearman correlation coefficient was used to assess the relationships between the percentage change in CO and IVC related parameters. Receiver operating characteristic (ROC) curve analysis was performed to test the predictive value of IVC related parameters, and the areas under the curve with 95% confidence interval (CI) were calculated. The best cut-off value was determined by the maximum of the Youden index (sensitivity + specificity-1). Comparison of AUCs between two indicators was performed using the methodology proposed by Delong and his colleagues . The areP > 0.05).A total of sixty patients were recruited in this study, and four patients were excluded due to low quality of ultrasound images. Thus, fifty-six patients completed the present clinical study. Thirty-three mechanically ventilated patients (58.9%) and twenty-two spontaneously breathing patients after the tracheal extubation (39.3%) responded to fluid challenge Fig. . DemograP < 0.05). Meanwhile, the fluid challenge significantly escalated IVCmax and IVCmin in group R and HR in group NR  and 0.80 , respectively, which was not statistically different (P > 0.05), and were higher than that of CVP . The optimal cut-off value of cIVC1 to predict volume responsiveness was 15.32% with the sensitivity of 100% and specificity of 65%, respectively. The ΔIVC had the same specificity compared with cIVC1 when the cut-off value was 0.29 cm but a lower sensitivity of 85% .Baseline cIVC2 and IVCmin correlated significantly with the percentage change in CO after fluid challenge (P = 0.037). It is worth noting that there is no statistical difference in the AUCs between static indicator IVCmin and cIVC2, presenting similar diagnostic accuracy. The optimal cut-off value of IVCmin was 1.14 cm, with 86% sensitivity and specificity of 71%. The AUCs of both cIVC2 and IVCmin were statistically higher than CVP  which was higher than 0.76 (95% CI: 0.62–0.86) of ΔIVC , which was lower than 29 (51.8%) for ΔIVC, indicating that IVCmin had a better test utility  and 1.16 (95% CI: 1.05–1.28), respectively  via thermal dilution method. However, it is unrealistic to take a high risk of placing PAC in patients undergoing abdominal surgery. We performed triple measurements for every single parameter, and the average of these values was adopted in the end to ensure the accuracy of CO measurement.The IVC respiratory variability index was moderately predictive of postoperative volume responsiveness of patients undergoing abdominal surgery under artificially or spontaneously breathing. The cIVC and IVCmin seemed to be more clinically useful in predicting the volume responsiveness in the spontaneously breathing patient as opposed to the predictor of cIVC in mechanically ventilated patients.Additional file 1. Additional file 2.


There is lack of large data from South-Asian region on atrial fibrillation and it is imperative that clinical presentation, prognostic factors, management pursued, and outcomes are known for this part of the world. Once collective evidence for the region is known, region-specific guidelines can be laid forward.To evaluate clinical characteristics and prognostic factors of atrial fibrillation at a tertiary care center of Pakistan.This was a retrospective study conducted at a tertiary care center of Pakistan. Period of study ranged from July–December 2018. All hospitalized patients who were admitted with atrial fibrillation as a primary or associated diagnosis were enrolled.2DS2VASc and HASBLED scores were 4 and 2 respectively. More than one-third of patients had sepsis as a primary diagnosis (36.8%). The in-hospital mortality of patients with atrial fibrillation was 6.7%. Patients with new-onset AF had higher mortality. Sepsis and stroke were independently associated with a higher mortality. There was no significant difference in median CHA2DS2VASc and HASBLED scores for patients with new-onset and previously known AF. On discharge, 83% of the eligible patients received oral anticoagulation.A total of 636 patients were enrolled. The mean age was 68.5 ± 12 years and 49.5% (315) were male. 90.6% of the patients were admitted via emergency room. Majority (59.9%) had previously known AF and 40% developed new-onset AF during the hospital stay. Hypertension was the most common co-morbid condition (85.4%) followed by Diabetes Mellitus (40.1%). At least 9% had rheumatic heart disease. The median CHA2DS2VASC Score. Sepsis and stroke were independently associated with higher in-hospital mortality.There was higher prevalence of chronic co-morbid conditions in the studied population leading to a higher CHA •Sepsis and stroke are independently associated with higher in-hospital mortality in patients with atrial fibrillation.•There is higher prevalence of chronic co-morbid conditions in the studied population.•Hypertension is the most common co-morbid condition associated with atrial fibrillation. It has AF is the most frequent sustained arrhythmia identified in clinical practice . PatientWith increase in life expectancy, more people now live with chronic co-morbid conditions. Hence, the prevalence of AF is estimated to rise by at least 2.5-fold by 2050 . AlthougClinical research providing framework for guidelines over the last 2 decades are largely based on data from regions other than South-Asia . There i2Study Population: It was a retrospective observational study conducted at a tertiary care teaching hospital of the country. The study was approved by the ethical review committee of the hospital (ERC No. 019-1008-2905). Both male and females, age ≥18, who were found to have atrial fibrillation as a primary or associated diagnosis were included. Diagnosis of AF was confirmed on a 12-lead ECG. Hospital record for 651 patients meeting the inclusion criteria was retrieved from the electronic medical record system for a study period from July 1, 2018 to December 31, 2018. Fifteen patients were excluded who did not have electrocardiographic evidence of atrial fibrillation  dimension, LA volume index and left ventricular (LV) systolic function.Patients were labeled as diabetic if they had HbA1c > 6.5 gm/dl or were already on treatment for DM. Hypertension was defined as an average of two readings of systolic blood pressure ≥140 mmHg, a diastolic blood pressure ≥90 mmHg or if patient was already taking antihypertensive medications. Coronary artery disease was defined as ≥50% stenosis in at least one of the epicardial coronary arteries. Cardiomyopathy was defined as LV ejection fraction of ≤50%. Chronic obstructive pulmonary disease was defined as a forced expiratory volume in 1st second to forced vital capacity ratio of <70% of the predicted value. Patients were labeled hyperthyroid if they had low serum TSH and high serum concentration of free T4 or T3 as per the laboratory reference range.In hospital Monitoring: All patients were followed from the time of inclusion to the time of discharge or till inpatient death. Hemodynamic parameters including heart rate and blood pressure were recorded at the time of inclusion for patients with known atrial fibrillation and at the time of onset of arrhythmia for those with new onset atrial fibrillation. Patients’ treatment records were retrieved. Complications related to atrial fibrillation, or its treatment were also recorded.Statistical Analysis: After creating a database, the data was encoded. All statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) version 23. Continuous variables were expressed as mean value ± standard deviation and categorical variables were expressed as frequencies and percentage. Multivariate logistic regression was done to analyze the risk factors and predictors of in-hospital mortality and p value of <0.05 was considered significant.clinicaltrial.gov (UIN number: NCT05082558).Ethical approval was obtained from the ethical review committee of the hospital. The work has been reported in line with the STROCSS criteria . This st3Baseline characteristics: From July–December 2018, a total of 36,925 patients were admitted to the hospital. Atrial fibrillation was present in 1.72% (636) of the patients (patients . Out of Diabetes mellitus was found in 372 (58.5%) patients, hypertension in 543 (85.4%) patients, coronary artery disease in 201 (31.6%) patients and chronic kidney disease was found in 66 (10.4%) patients. A total of 117 (18.4%) had prior CVA, 39 (6.1%) patients had thyroid disorder and 57 (9%) had prior rheumatic heart disease.Of 636 patients, 381 (59.9%) patients had previously diagnosed persistent or paroxysmal atrial fibrillation and 255 (40.1%) developed new onset atrial fibrillation during the hospital stay. Baseline characteristics of both the groups  were as shown in Treatment: Out of 636 patients, 489 (76.9%) patients had well controlled ventricular rate (<110beats/min) and rest of them (147) had uncontrolled ventricular rate. During the hospital stay, beta blockers were given in 465 (73.1%) patients, (relative contraindication to beta blockers was present in 162 (25.5%) patients), non-dihydropyridine calcium channel blockers in 63 (9.9%) patients. None of the patients received digoxin and none required emergency electrical cardioversion.2DS2VASc score in our study population was 4 with an interquartile range (IQR) of 7and median HASBLED score was 2 with an IQR of 4. Out of 321 female patients, 303 (94.4%) had a CHA2DS2VASc score of ≥2 and oral anticoagulation was prescribed to 222 (73.2%) on discharge. Among male participants, 306 (97.1%) had a CHA2DS2VASc score of ≥1 and 207 (68%) of them received anticoagulation.Median CHAIntravenous amiodarone was given in 255 (40.1%) patients, 246 of them were those with new onset AF. Mean ventricular rate of these patients was 152 ± 17 bpm and mean systolic blood pressure was 103 ± 6.4 mmHg at the time when amiodarone was started. Around 82% of the patients received intravenous amiodarone bolus (150 mg) before starting on infusion at 1 mg/min for 6 h followed by 0.5 mg/min for next 18 h. Out of 246 patients with new onset AF who received intravenous amiodarone, 60 (24.3%) reverted to sinus rhythm within 6 h of infusion and 182 (74%) were found in sinus rhythm at the end of 24 h of infusion. After intravenous infusion, oral amiodarone was continued in 142 (58.9%) of the patients during the hospital stay.Of all the study population, 429 (67.5%) patients got oral anticoagulation on discharge and 93 (14.6%) patients did not get anticoagulation due to contraindications. Contraindications included hematuria, gastrointestinal bleed, coagulopathy, and previous intracranial hemorrhage. Novel oral anticoagulants were prescribed to 336 (52.8%) patients and 93 (14.6%) patients received vitamin K antagonist on discharge. More women received anticoagulation on discharge as compared to men .Table 2CComplications: Hematuria was the most common complication observed in a total of 32 (6.6%) patients during the hospital stay, requiring transient discontinuation of anticoagulation. 5 (1.04%) of the patients developed gastrointestinal bleed requiring blood transfusion. None of the patients developed intracranial or retroperitoneal bleeding. No significant drug related side effects were found in our study population and none of the participants developed CVA during the hospital stay  patients had in-hospital death and sepsis/septic shock was the major cause of in-hospital mortality. Sepsis was more common in patients with new-onset AF, resulting in higher in-hospital mortality in the group as compared to those with previously known AF.Predictors of In-hospital Mortality: On multivariate logistic regression analysis, sepsis and previous cerebrovascular accident were found to be independently associated with in-hospital mortality, with odds ratio of 3.953 (95% CI 1.993–7.880) and 2.225 (95% CI 1.022–4.841) respectively. There was no association between in-hospital mortality and other co-morbid conditions such as hypertension, coronary artery disease, chronic kidney disease, gender, and thyroid disorders  received anticoagulation on discharge. Haq et al. reported that only 48% of the study population was discharged on oral anticoagulation [2DS2VASc risk score was calculated for each patient. NOACs  were the most used anticoagulant in 336 (78%) of patients.In our study population, 83% of the eligible patients (CHAgulation . Moreovegulation . This hi2DS2VASc score with a median score of 4 (No difference was observed between new onset and previously known AF patients). Tischer et al. from Germany reported a mean CHA2DS2VASc of 3.04 ± 1.42 in 150,408 AF patients admitted to a tertiary care hospital [2DS2VASc score can be explained by the higher prevalence of co-morbid conditions such as hypertension (85%), DM (58.5%) and prior CVA (18.4%). The relatively higher prevalence of prior stroke in the study population points towards late diagnosis once complication of AF had already happened. Considering higher prevalence of risk factors associated with AF in the region, it is imperative that an effort for early recognition of AF is made at a community level.Our study population had a higher CHAhospital . With thOur study highlighted a higher conversion-to-sinus rate (74%) with use of amiodarone along with a relatively lower rate of recurrence during the same hospital stay (7.4%). In a study by Mitric et al., 95% of the patients with new onset AF cardioverted to sinus rhythm with amiodarone, however AF recurred in 51.4% patients . In a stIn our study population, moderate to severe mitral stenosis was seen only in 5.2% of patients and only 9% has a diagnosis of rheumatic heart disease (RHD). These findings are quite different from the Haq et al. study which showed 27% of patient with rheumatic heart disease . This maIn our study population, majority of patients with new onset atrial fibrillation had underlying sepsis. The in-hospital mortality was more than 6% in our population which is higher than the comparative studies. In a population-based study from Korea, patients with AF had four times higher mortality as compared to general population and cerebrovascular accident (CVA) was the most common cause of death in patients with AF . In a syTo our knowledge, this is one of the largest hospital-based study on AF from Pakistan. This study identifies important information regarding the clinical characteristics and management of AF patients in Pakistan.5This is a single centered retrospective observational study and may not represent the entire population of the country. There was no control group in the study, and it was not possible to establish the causation of atrial fibrillation with mortality. Long-term follow-up was not available to assess the complications of AF and drug compliance.62DS2VASc score and multiple comorbid conditions. Non-valvular atrial fibrillation was much more common than the valvular atrial fibrillation. Sepsis and prior cerebrovascular accidents were independently associated with in-hospital mortality in our study population. One-fifth of hospitalized patients with AF had history of CVA. However, the anticoagulation rate on discharge among eligible patient was around 83%. There is a need to recognize patients at risk of developing atrial fibrillation and its associated complications. A population-based study is required to confirm above findings. This shall lead to the foundation of local guidelines for the management of AF.The studied population had a higher CHAEthical review committee of the Aga Khan University Hospital.No funding acquired for this study.ERC Number: 019-1008-2905.IA: Study conceptualization, data management and analysis and manuscript writing.AN, PS, MH, FS collected the data and contributed to the data analysis and literature search.HS, GA, AF contributed to the manuscript review and literature search.AH: critical appraisal and manuscript review.YS: Supervised from conceptualization to final execution and manuscript writing.Consent not applicable as no direct intervention or interaction with human subjects.NOT APPLICABLE.clinicaltrial.gov.1. Name of the registry: 2. Unique Identifying number or registration ID: NCT05082558.https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BBXV&selectaction=Edit&uid=U0005QOF&ts=2&cx=-3zumv5.3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Dr. Yawer Saeed.None of the authors has any conflict of interest to reveal.


Salmonella have been linked with a variety of pork products. This study evaluated the effects of a Salmonella-specific lytic bacteriophage and lactic acid (LA) on Salmonella Enteritidis, Salmonella Montevideo, and Salmonella Heidelberg growth on raw pork loins. Pork loins were cut into approximately 4 cm thick slices. Pork slices were randomly assigned to five treatment groups  with six slices per group per replication. Pork loins were inoculated with 106 CFU/mL of Salmonella spp. and stored at 4 °C for 30 min. After 1 h of treatment application and marination, phage 5% significantly (p < 0.05) reduced the surface bacterial population by 2.30 logs when compared with the control group. Moreover, the combined treatment of LA 2.5% + phage 5% significantly (p < 0.05) reduced the surface bacterial population by more than 2.36 logs after 1 h of marination. In the post-tenderization surface samples, the combination of both phage and LA showed a significant reduction (p < 0.05) when compared with the control group. However, the treatments had no effect (p > 0.05) when analyzing the translocation of pathogens on pork loins.Bacterial food poisoning cases due to  Pork is the most widely eaten meat globally, and recent data show that consumption has more than doubled in developing countries ,2. FurthSalmonella continues to be a leading cause of domestically acquired foodborne illness resulting in hospitalization, which indicates that more research needs to be conducted [Salmonella spp. continues to be one of the most common bacterial food contaminants over time [Salmonella enterica serovar Enteritidis accounts for almost half of all human Salmonella infections worldwide [Salmonella-related outbreaks that infected over 1100 people from 49 states and caused two deaths. [Salmonella is often linked to outbreaks detected in meat and meat products [Salmonella and 4% of Salmonella Enteritidis outbreaks [onducted . Likewisver time . Among torldwide . In 2019 deaths. . While tproducts . LikewisSalmonella infection causes salmonellosis and manifests into several disease syndromes, including gastroenteritis, septicemia, and typhoid fever [Salmonella serotypes is a global public health concern and poses a severe threat to humans through the food industry [id fever . Most caid fever . The devid fever . Most peid fever . Howeverindustry .Salmonella has evolved to develop new genes to help it to withstand challenging environments, settle into a new environmental niche, and establish antimicrobial resistance [S. Typhimurium was identified as being likely associated with pork consumption [sistance . In a resumption . The devSalmonella spp. could help to increase the food safety of meat products.Meanwhile, the United States Food and Drug Administration (US-FDA) has approved several phage preparations for meat and poultry products as a food processing aid . NumerouSalmonella and other Salmonella enterica subspecies that can cause illnesses or hospitalization [Salmonella Enteritidis, Salmonella Montevideo, and Salmonella Heidelberg in marinated and tenderized raw pork loins.Lytic bacteriophages and lactic acid on poultry products have proven effective in multiple studies ,22. Howelization . Therefon = 6 per treatment; 30 total per replication) and randomly allocated to different treatment groups. Then, randomly assigned slices were prepared for inoculation and further processing.Raw pork loins were procured from a nearby grocery store and were transported under ice (<4 °C) to the food safety lab at Warren J. Baker Center for Science and Mathematics, Cal Poly. Upon arrival, the loins (pH 5.6–5.8) were portioned into ~4 cm thick slices ranging from 200 to 300 g per piece  in a final product at a targeted 10% uptake level. Based on the meat weight, a batch of the marinade was made on the same day and equally divided for five different treatments. Marinade pH was measured prior to (7.2) and after one hour of marination (6.8).A standard marination solution was prepared to deliver 0.35% sodium chloride  and 0.45% sodium tripolyphosphate , Salmonella Montevideo (S. Montevideo), and Salmonella Heidelberg (S. Heidelberg) were obtained from the Department of Food Science and Nutrition, California Polytechnic State University , San Luis Obispo, California. Throughout the experiment, strains were individually maintained on Tryptic Soy Broth .Three is study . Pure cu8 CFU/mL. Later, the cocktail was prepared in buffered peptone water  by mixing the three strains. Throughout the experiment, a final concentration of 1.0 × 106 CFU/mL of Salmonella cocktail was maintained in the BPW broth.To prepare a cocktail for meat inoculation, individual strains were grown separately in 10 mL of tryptic soy broth (TSB) and passaged three times at 37 °C for 18 to 24 h to reach a final concentration of 1.0 × 106 CFU/mL) of S. Enteritidis, S. Montevideo, and S. Heidelberg for two minutes following the dip inoculation method. After inoculation, slices were left for 30 min attachment at 4 °C. Later, pork slices were placed in a plastic container containing 0.35% sodium chloride and 0.45% sodium triphosphate to be marinated for 1 h. Plastic templates (5 cm × 10 cm) were used, along with microbial sponge sticks , to swab the pork slice surface (Pork slices from loins (pork samples) were experimentally inoculated in the cocktail (10 surface .n = 6) per replication. Before the treatment application, pork slices were first kept in the marinade. The solutions of 5% (1 × 108 PFU (plaque-forming unit)/mL on meat surface) lytic bacteriophages  and 2.5% LA  were prepared based upon the manufacturer’s recommendation of 10 μL/cm2 surface application. Lactic acid and bacteriophage applications were performed by pipetting the required volume of each treatment onto the pork slices. Treated pork slices were kept at refrigeration temperature with marinade for 1 h before sampling.Raw pork slices were randomly assigned to one of the five treatments  water, 2.5% LA (lactic acid), 5% phage, 2.5% LA + 5% phage; Salmonella spp. Three loin slices were then randomly selected within each treatment group after 1 h to be removed and sampled for post-treatment surface attachment. Before swabbing the meat surface for Salmonella, the sponge was squeezed inside the bag to remove the excess BPW; the swab was then taken from inside a template (50 cm2) of the raw pork slice. The sponge stick was returned to the collection bag and placed in the Stomacher®  at 230 rpm for two minutes. Serial dilutions were then plated onto XLD  agar plates in duplicate, incubated at 37 °C, and typical Salmonella colonies were enumerated (CFU/cm2).After the application of treatments, slices were stored at 4 °C for 1 h prior to sampling. Microbial sponge sticks were used for a swab collection from each raw pork portion . One por2) was used to swab the entire surface, and the sponge was placed in the stomacher at 230 rpm for 2 min. After swabbing the surface, a sterile subsection from the centermost portion of the slice was obtained using flame-sterilized knives  for the bacterial translocation study. For the entirety of the experiment, one manual tenderizer was used and sterilized between treatments. Tenderized samples were then swabbed over the entire surface using a sponge stick moistened with 10 mL BPW. A template  and triple sugar iron  for purification and biochemical confirmation. Before the statistical analysis, 10 CFU/cm2 for surface and log10 CFU/g for cores. Data were analyzed using the PROC MIXED procedure of SAS . The least-square means were generated using the LSMEANS statement, separated using the PDIFF function and considered significant at an α of 0.05.The experiment was replicated three times and designed as a randomized complete block design. The repeated replication served as different blocks. Treatments were assigned at random within the blocks. Storage length and marination length served as independent variables. Response variables of interest included bacterial surface attachment , meat pH, and internal pathogen concentration (1 h post-tenderization cores). Before statistical analysis, bacterial cell counts were converted to logSalmonella spp. on randomly assigned loin slices to the different treatments prior to application ranged from 3.30 to 4.55 log10 CFU/cm2 (p < 0.05) the surface microbial population in the marinated pork loins by 2.3 logs in one hour compared with the control group. However, it should be noted that the control group also experienced a decrease in CFU from the initial surface attachment of 4.55 logs to 3.90 logs after 1 h. In addition, the combination of both lactic acid (2.5%) and lytic bacteriophage (5%) on the pork loins also resulted in a significant reduction (p < 0.05) in Salmonella spp. from the surface by 2.35 logs after 1 h of marination  in Salmonella spp. on surface attachment post-tenderization was observed when 5% phage and the combination of 2.5% LA + 5% phage was used on the pork loins (p > 0.05) in the Salmonella spp. population on the post-tenderized loin surface  reductions in surface-attached Salmonella spp. after 1 h of pork marination compared with the control. After 1 h, the 5% phage and combination of 2.5% LA + 5% phage were able to reduce the surface-attached pathogen by 1.72 and 1.77 logs, respectively  on the translocation of Salmonella spp. measured in log10 CFU/g in the internal cores  [Salmonella counts in fresh, chilled pork. A consistent 1 log reduction in Salmonella load has been reported in four meat types  when applying bacteriophages on trim and thighs prior to grinding [Due to the unique ability to infect and lyse specific bacterial cells, bacteriophage applications have become a suitable food safety invention for the food industry . Many st. (2017)  reportedgrinding , which iSalmonella spp. when studying the translocation of the pathogen post-tenderization. Possibly, higher dosages of lytic bacteriophage and lactic acid would substantially decrease microbial translocation on pork loins. More research is needed to evaluate the correct dosage of lytic bacteriophage combined with lactic acid to considerably reduce the translocated Salmonella spp. in pork meat. In theory, manual tenderization with the help of a tabletop tenderizer and increased marination length would enhance pathogen internalization on meat products. Previous studies have shown that microbial internalization is possible on various processing technologies [Salmonella [Salmonella populations increased 2.0 log CFU/g in tenderized rib eyes cooked to 37.8 °C when held at 60.0 °C for 8 h. Therefore, mechanical tenderization, shelf life, and temperature are all factors that may pose a food safety risk to consumers in terms of inadequate lethality and/or subsequent outgrowth of Salmonella.In this study, the antimicrobial treatments did not significantly reduce nologies ,34,35. Llmonella ,37. Perhlmonella  demonstrSalmonella on the surface of pork loin. This research has found that the combination of 5% lytic bacteriophage and 2.5% lactic acid significantly reduced the Salmonella cocktail (p < 0.05) on raw pork loin meat surfaces by 1.75 logs but failed to significantly reduce Salmonella spp. in the internal cores of pork loin after manual tenderization. According to the data, lactic acid is not a suitable treatment for pork loins but could be an option if combined with lytic bacteriophages. While not formally assessed, minimal negative impacts were caused by the usage of lactic acid and lytic bacteriophages on pork loins regarding product color. The results from this study have a significant influence on the reduction in Salmonella prevalence in pork and can be applied to the U.S. pork industry, extending to domestic and export markets. The reduction in Salmonella spp. on raw pork loins will enhance food safety and reduce the number of foodborne infections.Lytic bacteriophages and lactic acid as antimicrobial interventions effectively reduce


To synthesise EQ5D health state utility values in Chinese women with breast cancer for parameterising a cost utility model.2 statistic and sensitivity analysis and meta-regression were conducted.Eligible studies had to report health state utility values measured by EQ-5D in Chinese women diagnosed with breast cancer. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS). Data from single arm studies was pooled using meta-analysis of single proportions to provide overall point estimates and 95% confidence intervals for fixed and random effects models using the inverse variance and Der Simonian-Laird methods respectively. Heterogeneity was evaluated using the I2 =95%); for 37 to 60 months 0.89 ; for more than 60 months 0.86 . Mean utility for chemotherapy was 0.86 ; for radiotherapy 0.83 ; surgery 0.80 ; concurrent chemo-radiation 0.70  and endocrine therapy 0.90 . Conclusion: This study synthesises the evidence for health state utility values for Chinese women with breast cancer which is useful to inform cost utility models.Five papers were included, when all studies were combined  the mean utility  for random effects model was 0.83 ; for TNM 0-1 0.85 ; for TNM II 0.85 ; for TNM III 0.83  and for TNM IV 0.73 .The utility of patients in State P (first year after primary breast cancer) 0.84 ; in State R (first year after recurrence) 0.73 , in State S (second and following years after primary breast cancer or recurrence) 0.88 ; and in State M (metastatic disease) 0.78 . Mean utility for duration since diagnosis 13 to 36 months was 0.88 (0.80, 0.96, IThe online version contains supplementary material available at 10.1186/s12885-021-09140-5. Breast cancer has now overtaken lung cancer to become the most commonly diagnosed cancer in women in China , 2. The This is particularly relevant now, as pharmacoeconomics is playing an increasingly important role in China, evidenced by the recent 2020 guideline that recommends cost-utility analysis and quality adjusted life years for pharmacoeconomic analysis , 5. It aCost utility analyses require health state utility values. There are few studies that measure health state utility values of Chinese women with breast cancer and these few studies, when taken together may provide an estimate of effect which can be useful to inform decisions making. To parameterise a cost utility model when multiple primary studies are available, performing an evidence synthesis with a single arm pooling , can provide an acceptable estimate and is in keeping with best practice recommendations for modelling . In the Literature search strategy: Pubmed  was searched (28.05.2020) from January 2002 to May 2020. The Cochrane and Centre for Reviews and Dissemination databases were searched , Cochrane Central Register of Clinical Trials, Health Technology Assessment (HTA), Economic Evaluation (NHS EED) was searched on 20.11.2020). The literature search strategy was replicated on 20.08.2021 for the preceding year, no new results were identified. Citation snowballing was used to identify additional papers. The search terms in Table 1.2020. TEligibility criteria: pre-specified selection criteria were applied. Included studies had to be conducted in China (or Asian countries with >80% Chinese participants), had to use the EQ5D instrument to measure Quality of Life and had to report health state utility values of women with breast cancer. Included studies needed to report essential summary measures required for meta-analysis (mean utility and variance).Study selection: Titles and abstracts were screened by two trained, independent reviewers . Titles/abstracts of unclear eligibility were included at this stage. Full texts were retrieved and reviewed by two independent reviewers . Discrepancies were resolved via an independent third reviewer (MD).Data extraction and quality assessment: Data was extracted and verified independently by two reviewers . Data fields extracted included study location and design, population demographics, the description of the related health state, sample size, mean utility and variance. Risk of bias was assessed using the Newcastle Ottawa Scale (NOS) which is applicable for assessing the level of bias in single-arm non-randomized studies . The NOS2 statistic and where possible meta-regression of covariates was conducted in OpenMeta [Meta-analysis: The meta-analysis was considered feasible if two or more studies reported utility for breast cancer and was conducted according to international recommendations . Data frOpenMeta . Meta-anStudy selection: A total of 58 papers were identified and 53 of which were excluded during title/abstract screening and full text assessment. In total, nine papers were excluded because they focused on incorrect population (conducted outside China/did not include more than 80% of Chinese respondents/focus on other cancers). Nineteen studies did not report quality of life data or derived it according to other disease-specific or generic instruments. Sixteen studies did not report sufficient measures of effect and variance and had no usable data. Eight studies were the incorrect study design, six of which were economic evaluations/cost effectiveness studies and two of which were pilot studies. One duplicate study was identified which reports the same patient sample  and values, the most recent paper has been included in the analysis , 20. FivStudy overview: Four of the five studies were full published papers , 23, 24 Quality assessment: With respect to sampling bias: Ou is considered to be at high risk of being non-representative of the general population because it includes patients referred to a specialist clinic with hormone receptor positive and human epidermal growth factor receptor 2 negative subtypes of breast cancer only. Furthermore, although the study includes 100% Chinese patients, it is conducted in Taiwan. Cheung is considered to be at moderate risk of bias because it includes 81% of Chinese patients from Singapore , 24..Four of the studies were judged to be at low risk of attrition bias: Wang did not report the number of participants that utility values were elicited from and Ou  neglecteFour of the studies were considered at low risk of bias with respect to timing of administering the EQ5D. Li and Yang had similar distribution of patients according to time since diagnosis. Approximately a third were less than 12 months since diagnosis (31% vs. 31%); a third were 13-36 months since diagnosis (32% vs 33%); remainder of patients were distributed evenly across 37 to 60 months (19% vs 17%) and more than 61 months since diagnosis (18% vs 20%) for Li and Yang respectively. Ou study was considered to be at moderate risk of bias because more patients were longer since diagnosis compared to Li and Yang: 34% of patients were within 36 months of diagnosis, 39% were 37-60 months, 14% were 84-108 months and 13% were more than 108 months since diagnosis. According to Wang, 9% of respondents were pre-treatment, 64% were having treatment, 21% were after treatment and 6 % were during follow-up. Cheung did not explicitly state duration, however 48% were undergoing treatment, 33% were having palliative treatment and 19% were having follow-up or no treatment. Both studies were considered to be low risk of bias. No issues of selective reporting were raised, except for Yang due to the failure to report details on attrition. The risk of bias assessed by NOS is shown in Table Study characteristics: The average age of study participants ranged between 48 and 55 years, with the majority of participants being married (range 71% to 92%). Participants from Taiwan  and SingHealth state utility values: Utility values from the five included studies are shown in Table 2 = 99%) for random and fixed effects models respectively shown in Table Meta-analysis: When mean utility from all patients in the five studies are combined  the mean utility  is 0.83  and 0.82 ; for TNM II  0.85  and 0.81 ; for TNM III (n=811) 0.83  and 0.80  and TNM IV (n=297) 0.73  and 0.71  for random and fixed effects models respectively shown in Table When studies were combined according to TNM stage, for TNM 0-1 and 1 (n=721) mean utility was 0.85  and 0.85 0.84, 0.86, I, I2 =98%2 =71%); for state S (n=503) 0.88  and 0.88 ; for state R (n=85) 0.73  and 0.73 ; for state M (n=184) 0.78  and 0.78  for random and fixed effects models respectively shown in Table Li and Yang reported data by cancer state, mean utility for state P (n=282) was 0.84  and 0.85 0.82, 0.87, I, I2 =71%2 =95%); for 37 to 60 months (n=186) 0.89  and 0.90 ; for more than 60 months (n=161) 0.86  and 0.84  for random and fixed effects models respectively shown in Table Li and Yang reported data according to time since diagnosis. Mean utility for duration 13 to 36 months (n=263) was 0.88  and 0.89 ; for radiotherapy (n=332) 0.83  and 0.90  and for surgery (n=891) 0.80  and 0.77 . Li and Wang reported concurrent chemo-radiation therapy (n=73) 0.70  and 0.70 . Li and Ou reported results for endocrine therapy (n=180) 0.90  and 0.92  for random and fixed effects models respectively shown in Table Li, Ou and Wang reported data according to treatment regimen. Mean utility for chemotherapy (n=850) was 0.86 0.79, 0.92) and 0.85  see supplement). Chemotherapy for example has been identified as associated with poor quality of life (Ou). The study with the lowest proportion of patients having chemotherapy  was Wang (up to 30%); Yang (up to 31%); Li (47%); Cheung (50%) and Ou (70%), . Other studies have noted that chemotherapy is associated with poorer quality of life (Ou). Not only are different treatment combinations provided, but the treatment setting also varies, for example in the Li study, 100% were inpatients compared to 29% in Cheung and 16% in Yang. Inpatient/outpatient mix is not reported for Ou and Wang. We can hypothesise that inpatients are “sicker” than outpatients and hence have lower utility. Another source of variability that it is not possible to explore in our analysis is the breast cancer subtypes. Ou included 100% patients with breast cancer subtypes HR-positive/ HER2-negative; (see . ChemothIt is important to emphasise that in spite of the heterogeneity, the mean values do not vary greatly. A further limitation of our study is that the individual studies report mean and standard deviation, assuming normal distribution for their own analyses and the same assumption has been made for our analysis, however the ceiling effect of utility is well documented. The reader should be aware that utility measured with instruments other than EQ5D will likely give different results .To the best of our knowledge there is no other meta-analysis of EQ-5D utility values specific to Chinese patients with breast cancer. Peasgood et al performed a meta-analysis of health-related quality of life in breast cancer patients more broadly, including all countries and all empirical health-related quality of life measuring instruments . They idThis study provides a meta-analysis of health state utility values measured by EQ5D by patients identifying as Chinese with breast cancer which may be used to inform cost utility models.Additional file 1.