Acute gastroenteritis is a global public health concern. This study aimed to analyze the trend and characteristics of acute viral gastroenteritis through a national surveillance network. Enteric viruses were detected in 9510 of 31,750 (30.1%) cases assessed from 2013 to 2019 by EnterNet. The most prevalent pathogens were norovirus (15.2%) and group A rotavirus (9.7%); most infections were reported in 2017 (34.0%). Norovirus and rotavirus coinfections were the most common. Norovirus infections were prevalent among 1‐year‐old children (1835 out of 9510 cases) during winter, and group A rotavirus infections were common during spring. Seasonality was not observed among enteric adenovirus, astrovirus, and sapovirus. The prevalent viral genotypes detected included norovirus GII.4, enteric adenovirus F41, astrovirus genotype 1, and sapovirus GI.1. However, changes in enteric virus trends were noted during the study period. Norovirus prevalence extended into spring, and new genotypes of enteric adenovirus, astrovirus, and sapovirus were identified. These surveillance data elucidate enteric virus epidemiological characteristics. It is known to occur due to complex factors such as public health and climate.Viral gastroenteritis is prevalent in winter with the cooler temperature and tends to decrease with an increase in temperature. The seasonality may vary depending on the region.In Korea, the nationwide acute diarrhea surveillance system (EnterNet‐Korea) has been operational since 2007. In total, 17 institutes of health and environmental research and 70 hospitals have collaborated to monitor the pathogens causing acute intestinal infections. The surveillance system curates and analyzes data online and shares information in real time. This study aimed to analyze the trends and characteristics of viral intestinal infections in Korea from surveillance data obtained from 2013 to 2019.22.1Fecal samples were obtained from patients with symptoms of acute intestinal infection included in the nationwide surveillance system. Acute gastroenteritis was defined as primary symptoms including diarrhea, vomiting, abdominal pain, and nausea.The survey was conducted for 7 years from 2013 to 2019, and fecal samples were collected from 70 hospitals nationwide from patients meeting the defined criteria for acute enteritis every week. Samples were transported to 17 institutes of health and environmental research immediately on collection or within a week and maintained at 4°C. Viral detection was carried out using the standardized surveillance protocols, and the results were submitted to the EnterNet system along with information regarding the sample.2.2One gram of fecal sample was placed in 9 ml of sterile phosphate‐buffered saline  and sufficiently vortexed to prepare a 10% fecal suspension, which was then centrifuged at 4°C and 3000 rpm for 15 min to extract the supernatant containing the viruses. In the antigen detection test, the pretreated fecal supernatant was used immediately. For genetic analysis, nucleic acids were extracted from the pretreated solution using the commercially available nucleic acid extraction kit, that is, NucleoMag 96 virus kit (Macherey‐Nagel), in accordance with the manufacturer's instructions, using 200 µl of the pretreatment solution. The final nucleic acid extract was 50 µl and was stored at −70°C until subsequent use.2.3For virus detection, antigen detection and gene detection were performed. RVA and HAdV antigens were detected using an enzymatic immunoassay. Pretreated 10% fecal supernatants were assessed using a RIDASCREEN EIA kit (R‐Biopharm). Gene detection was performed for NoV, HAstV, and SaV. Norovirus genotypes GI and GII were simultaneously detected using a commercially available real‐time reverse transcription PCR (RT‐PCR) assay, that is, AccuPower® Norovirus Real‐Time RT‐PCR Kit (Bioneer) and PowerCheck™ Norovirus GI/GII Multiplex Real‐time PCR Kit (Kogenebiotech). HAstV and SaV were detected through RT‐PCR analysis using specially generated primers  cases. NoV was the most frequently detected pathogen, found in 4802 (15.2%) cases, followed by RVA in 3056 (9.7%) cases. HAdV and HAstV were detected in 800 (2.5%) and 595 (1.9%) cases, respectively. SaV was detected in 257 (0.8%) cases. An annual average of 4510 samples was submitted. However, the system was reorganized after 2016 to secure 3000 samples per year. Owing to the reduction in the number of samples, only nationwide data, and not regional data, were analyzed  and 2018 , the detection rate was similar. The average detection rate of NoV was 15.2% (±2.4); however, the rate varied from year to year. Except in 2013, NoV was the most frequent pathogen, and the pathogen detection rate was the lowest at 11.8% (414/3520 cases) in 2018. RVA continued to decrease until 2016  from a high detection rate of 13.9% (1118/8018) in 2013. The detection rate increased temporarily in 2017 , but decreased again, being significantly lower in 2019 . Similar to NoV, the detection rate of HAdV periodically increased and decreased. In 2014, 2016, and 2018, the HAdV detection rate increased to 3.1% (186/5915), 4.2% (142/3360), and 3.8% (134/3520), respectively. HAstV displayed a detection rate of less than 2% until 2015, but a detection rate of more than or equal to 2% from 2016. SaV displayed an average detection rate of less than 1% until 2016 where it was detected at 1.3% (45/3360) in 2016, 1.0% (37/3757) in 2017, and 1.7% (49/2827) in 2019  at 1 year, followed by a high detection rate of 27.9% (2649/9510) at 0 years. The prevalence of NoV infections was the highest at 1 year of age at 19.3% (1835/9510); RVA, 0 years at 10.5% (994/9510). HAdV and SaV detection rates were as high as 3.1% (292/9510) and 1.0% (93/9510), respectively, at 1 year of age; HAstV, 1.8% (169/9510) at 0 years of age, similar to RVA  cases, and mixed infections were detected in 717 cases (8.2%). Among cases of single infections, NoV presented a high rate of 51.5% (4531/8793 cases); RVA, 32.1% (2823/8793 cases). Mixed infections were confirmed in 355 fecal samples, mostly involving two pathogens . NoV and RVA  were the most frequent, followed by NoV and HAstV . Furthermore, three viruses were detected simultaneously in seven fecal samples  and February , corresponding to winter in Korea. In summer, the lowest detection rate was recorded in July . NoV, RVA, and HAdV displayed clear seasonality with relatively high detection rates. However, seasonality and periodicity were not observed for HAstV and SaV owing to the low detection rates of these viruses  and January (31.6% ± 5.3). However, in 2018, the detection rate increased from end‐November 2018 until early June 2019. RVA displayed a high detection rate between March and May during spring and then decreased during early summer. In particular, the RVA detection rate peaked in March (23.9% ± 6.2). HAdV displayed a relatively high detection rate during summer and autumn; from January to July, its average detection rate was less than 2.0%, but it was high in August (3.4% ± 1.7) and October (4.0% ± 3.0).3.6Genotypes were confirmed in 5508 samples of four viruses except for RVA Table . NoV genHAdV genotypes were analyzed in 618 of 801 (77.2%) positive cases, revealing that F41  was the most prevalent genotype, followed by A31  and F40 . In 55 (8.9%) cases, B1.3, B1.7, C1, C2, C5, C6, and E4 were also identified to cause respiratory symptoms. In particular, in the past 3 years (2017–2019), in addition to the HAdV F41 genotype, fecal samples have revealed numerous genotypes of HAdV‐B and C types corresponding to the respiratory adenovirus.HAstV genotypes were analyzed in 522 of 595 (87.7%) positive cases, revealing that Type 1 was the most prevalent genotype among 72.2% (377/522) cases, followed by Type 5  and Type 4 . Various genotypes were detected in the past 3 years. In 2014, 27 (34.2%) cases of Type 5 infections were detected, and the detection rates for this genotype were high in 2018 (8.8%) and 2019 (27.3%). Type 4 genotypes were detected in 2017 (21.6%) and persisted in 2018 (11.0%) and 2019 (5.5%) as well.SaV genotypes were analyzed in 220 of 257 (85.6%) positive cases, revealing the GI group in 79.5% (175/220) cases, GII group in 10.9% (24/220) cases, and the GV group in 3.2% (7/220) cases. In the GI group, the GI.1 genotype revealed the highest detection rate of 60.0% (132/220 cases).4Viral acute gastroenteritis is a prominent disease in children.Rotavirus vaccine has been introduced in Korea and infants and toddlers are becoming exposed to it. Since this surveillance project is not a prospective cohort study on vaccination, the direct effect of vaccines cannot be determined, but it was confirmed that the rate of pathogen detection had continuously decreased. As the detection period of norovirus has recently extended until summer, it was expected that the detection rate of rotavirus would also be delayed, but the correlation between the two pathogens was not confirmed. However, the yearly decrease in the detection rate of rotavirus may be due to vaccination, but it seems to be related to the report that the outbreak of rotavirus is delayed and moving.Around this time, enteric HAdV, HAstV, and SaV tend to have newer genotypes relative to the previous ones. The detection rate of HAdV B and C genotypes was increased in addition to that of the F genotype, which was the predominant genotype, along with the detection rate of HAstV Type 4 and Type 5. Furthermore, the emergence of new genotypes is associated with the prevalence of new pathogens.The present surveillance data potentially broaden the current understanding of the epidemiological characteristics of enteritis‐causing viruses. However, the surveillance data could not account for changes in the prevalence of NoV and new genotypes. The present data would help understand this epidemic by further analyzing the environmental factors associated with this disease, such as its correlation with weather‐related factors and the genotype epidemic period, along with continuous monitoring of the pathogen detection rate.Writing‐original drafting: Seung‐Rye Cho. Formal analysis and methodology: Su‐Jin Chae and Sunyoung Jung. Writing‐review and editing: Wooyoung Choi and Myung‐Guk Han. Obtained funding: Cheon‐Kwon Yoo. Conceptualization and supervision: Deog‐Yong


This retrospective cohort study evaluated the pathological response after CRT in relation to treatment factors and patient and disease factors in order to find useful indicators to further improve the efficacy of CRT and create tailored therapeutic approaches. To date, the optimal timing for surgery after CRT has not been established. In literature, there are controversial results regarding the risk of higher surgical morbidity and perioperative complications due to delayed surgery. In our study carried out on 269 consecutive LARC patients, among the items analyzed, an interval time from CRT to surgery of >8 weeks was the only independent significant factor for pCR and downstaging.Neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision is currently the standard of care for locally advanced rectal cancer (LARC)p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging . Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender ( Colorectal cancer is currently the fourth most common malignancy and the second cause of cancer mortality worldwide . For recNeoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision (TME) is the current standard of care for locally advanced rectal cancers (LARC) and for distal tumors close to the sphincter structure in order to achieve organ preservation ,4.p < 0.0001) with a median follow-up of 48 months [After preoperative CRT, 15 to 20 percent of pathological complete response (pCR) rates have been reported ,7,8. A p8 months . These f8 months .Moreover, the possibility of a complete response to the neoadjuvant therapy has led to investigation of the hypothesis of the non-operative management (NOM) approach for patients with clinical complete response (cCR) after CRT. Prospective series and a large systematic review revealed that a “wait-and-see” policy and organ-sparing options such as local excision of the tumor may be possible alternatives for patients who achieve cCR after neoadjuvant CRT ,12.In the last few years, various strategies have been tested to improve the efficacy of the neoadjuvant CRT and to personalize therapies, such as chemotherapy intensification and prolonged time interval to surgery.Chemotherapy intensification was investigated during CRT, before and after surgery. Several studies have evaluated the addition of platinum-based chemotherapy to fluoropyrimidine in combination with radiotherapy. In the CAO/ARO/AIO-04 trial, an increased compliance and higher rates of pCR rates were reached by adding oxaliplatin to CRT . Insteadp < 0.001) and 3-year DFS was significantly increased in the second group: 68.5 percent vs. 75.7 percent . A relevant increase in G4 neutropenia was recorded during CRT in the experimental arm (2.8% vs. 0% p = 0.02) [More recently, neoadjuvant therapy with mFOLFIRINOX before CRT was investigated in the PRODIGE 23 phase III trial. Patients were randomly assigned to receive preoperative CRT plus surgery, followed by adjuvant chemotherapy for 6 months or 6 cycles of mFOLFIRINOX, followed by the same preoperative CRT scheme plus surgery and adjuvant chemotherapy for 3 months. The ypT0N0 rate was 11.7 percent vs. 27.5 percent respectively ( = 0.02) .Another open issue in rectal cancer management is the optimal timing between the end of CRT and surgery. Many retrospective studies have suggested that the tumor response is time-dependent, proposing that lengthening the interval between the end of CRT and surgery may increase the rate of pCR ,20,21. IThe aim of this study is to define the potential benefit of the pathological response after neoadjuvant CRT in LARC patients in relation to treatment factors, such as chemotherapy intensification and time interval to surgery, and to patient and disease factors, in order to find useful indicators to further improve efficacy of CRT and create tailored therapeutic approaches.We performed a retrospective cohort study on LARC patients treated at Campus Bio-Medico University of Rome. Patient data were collected from clinical records. Patients signed informed consent to the use of their clinical data for scientific purposes. Inclusion criteria was: age > 18 years, clinical stage II  or III  invasive rectal adenocarcinoma with distal tumor border within 12 cm from the anal verge by proctoscopy. In all patients, staging was performed with a multilayer computed tomography scan (CT) of the chest, abdomen and pelvis with intravenous contrast, and pelvic magnetic resonance imaging (MRI) with intravenous contrast.Patients were treated using 3D conformal radiotherapy or intensity-modulated radiotherapy (IMRT). The total radiation dose was 50.4 Gy with conventional fractionation of 1.8 Gy daily, for five days a week, concurrent to chemotherapy. The occurrence and nature of any adverse events were recorded in accordance with the National Cancer Institute Common Toxicity Criteria scale . When multiple treatment-related adverse events of the same type occurred in the same patient, only the most severe ones were reported.After the completion of CRT, restaging was performed. Tumor response was defined in accordance with the World Health Organization (WHO) by MRI and CT scan. Surgery was performed according to the principles of TME. Evaluation of the pathological specimens included ypTpN staging, resection margin involvement (positive if ≤1 mm distance from tumor to margin), and tumor regression grade (TRG) according to the Mandard tumor regression grade scoring system .After resection, patients were evaluated according to the standard surveillance protocol of follow-up.The primary endpoint of the study was to evaluate the pCR rate  and the downstaging rate .Secondary endpoints were the overall survival (OS), the disease-free survival (DFS) and local control (LC).Patients were divided into two groups according to chemotherapy regimens concurrent to radiation therapy (“1-drug” group: continuous intravenous fluorouracil (5-FU) or oral capecitabine (CAPE); “2-drug” group: 5-FU or CAPE with intravenous platinum-based chemotherapy). Patients were also stratified into two different time intervals according to the time between the end of neoadjuvant CRT and surgery . Patients were also divided according to relationship to relevant pretreatment factors as gender, age (≤70 years vs. >70 years), pre-treatment clinical stage (II vs. III) and distance of tumor from anal verge (≤5 cm vs. >5 cm).All study sample characteristics were summarized with descriptive statistics.χ2 test. The level of heterogeneity indicated the variability among the groups.Evaluation of differences was performed with log-rank test. Heterogeneity among study groups were evaluated by Pearson’s p value of 0.05 was considered significant.Given that pCR and pathologic downstaging are known to be robust factors for early efficacy and long-term survival in LARC patients, in this study, the efficacy was measured through these two endpoints in order to assess both tumor and nodal clearance. Univariate and multivariate logistic regression analyses were used to model the pCR and the pathological downstaging probability using clinically relevant variables. Variables considered in multivariate analysis were selected by significance during univariate analysis. A two-sided Overall survival (OS) was determined from the day of the histological diagnosis. DFS was measured from the day of surgery to the observation of progression/recurrence, or to the last follow-up if no event was observed. OS and DFS curves were calculated with the Kaplan-Meier method.The statistical analysis was performed with the Statistical Package for Social Sciences, version 25 .The study protocol was approved by the independent ethics committee of Campus Bio-Medico University of Rome .From July 2007 to July 2018, 564 patients diagnosed with rectal cancer were treated with radiation therapy at Campus Bio-Medico University of Rome. Of these, 362 patients underwent neoadjuvant CRT. Seventy-three patients were excluded from the final analysis for lack of data related to pathological specimens and clinical follow-up. Twenty patients did not undergo surgery after CRT and were excluded from the evaluation. Consequently, 269 patients were analyzed. The demographic and clinical characteristics of these patients are listed in During CRT, the all-grade toxicities were hematological  and gastrointestinal (diarrhea 50%). Grade 2 and grade 3 leukopenia and neutropenia occurred in 6% and 3.7% of patients, respectively. Grade 2 and grade 3 anemia and thrombocytopenia occurred in 9.6% and 7.7% of patients, respectively. Grade 2 diarrhea occurred in 25.2% of patients and grade 3 in 4.4%. No grade 4 toxicity was reported .Three patients did not complete neoadjuvant CRT, one patient due to perianal abscess and two due to genitourinary disease not related to treatment (infective cystitis and urinary retention).In 32 patients with grade 2 and 3 gastrointestinal toxicity, the treatment was interrupted .As reported in Materials and Methods, patients were stratified into two different groups according to concurrent chemotherapy schedule (1-drug vs. 2-drug). Grade 2 and grade 3 acute hematological toxicity occurred in 19 patients (13.1%) who received 1-drug chemotherapy during radiotherapy and in 54 patients (43.2%) who received 2-drug chemotherapy. Grade 2 and grade 3 gastrointestinal toxicity rate was 20.1% in the first group and 40.8% in the second one (29 and 51 patients respectively).In the 1-drug group, radiotherapy interruptions related to adverse events occurred in 18 patients (12.5%) with a median time of interruptions of 4.6 days (range 1–14 days). Of 125 patients treated with 2-drug CRT, radiotherapy interruptions occurred in 14 patients (11.2%) with a median time of interruptions of 3.2 days (range 1–5 days). A total of 236 patients (87.7%) were operated by low anterior resection and 33 (12.3%) by abdominal perineal resection. All patients underwent TME. R0 resection was obtained for 261 patients (97%). One hundred and seventeen patients (43.5%) had acute postoperative complications (within 30 days after surgery). For the entire population, median time from the end of CRT to surgery was 9.3 weeks .As reported in Materials and Methods, patients were stratified according to interval time to surgery.In total, 100 patients (37.2%) underwent surgery with an interval time of ≤8 weeks and 169 patients (62.8%) with an interval time of >8 weeks. The acute postoperative complications rate was 46% (46 patients) for patients with interval time to surgery of ≤8 weeks and 42% (71 patients) for patients with interval time to surgery of >8 weeks. The most frequent causes of postoperative complications were fever  and anastomotic leakages .Among all patients of the study, 70 (26%) underwent postoperative chemotherapy.n = 70 patients). For patients who did not achieve pCR, TRG were as follows: TRG2 17.1%, TRG3 33.4%, TRG4 21.6%, TRG5 1.9%.Overall, pCR rate was 26% , pre-treatment clinical stage (II vs. III), distance of tumor from anal verge (≤5 cm vs. >5), time to surgery (≤8 weeks vs. >8 weeks) and concurrent chemotherapy schedule (1-drug vs. 2-drug) was detected by Pearson’s χ2 test .p = 0.012) and time to surgery (p = 0.029).There were no significant differences between the pCR and no-pCR groups in terms of clinical stage, distance of tumor from anal verge and concurrent chemotherapy schedule. Specifically, the pCR rate was 26.5% (38 patients) in the 1-drug group (5-FU or CAPE) and 25.6% (32 patients) in the 2-drug group (5-FU or CAPE with intravenous platinum-based chemotherapy). Of patients with TRG2, 24 were in the 1-drug group, 22 in the 2-drug group. A significant difference was found for gender (p = 0.015) and time to surgery  were significantly correlated to pCR. Logistic regression showed that other variables such as age and concomitant chemotherapy schedule were not significantly associated with pCR.The pCR rate was 19% (19 patients) for patients who underwent surgery with an interval time of ≤8 weeks group and 30.1% (51 patients) for patients who underwent surgery with an interval time of >8 weeks, as shown in p = 0.01) and interval time to surgery of >8 weeks  were confirmed at multivariate analysis, and were the only remaining correlated factors with pCR . The downstaging rate according to chemotherapy schedule was 76.3% and 74.4% in 1-drug group and 2-drugs group, respectively.The downstaging rate in relation to time intervals to surgery resulted in 65% in the group with time ≤8 weeks and 81.6% in the group with time >8 weeks.p = 0.05) and interval time to surgery of >8 weeks  were significantly correlated with downstaging and, of these factors, a resting time of >8 weeks was confirmed at multivariate analysis   .n = 22; 46.8%) and liver . A total of 42 patients (15.6%) died; 13 deaths were tumor related, and 29 were due to intercurrent diseases. Of the remaining 227 patients, 204 (75.8%) are alive without evidence of disease.The median follow-up of the entire population was 51.1 months . At time of analysis, only 16 patients (6%) had a follow-up period of less than 1 year, while 119 patients (44%) had a follow-up period of longer than 5 years. A total 56 (20.8%) had a progression of disease. Patterns of failure included the following: 9 (3.4%) local recurrence, 47 (17.4%) distant metastases, 6 (2.2%) both local failure and distant metastases. The most common sites of distant metastases were lung  and local control (LC) was analyzed.p = 0.05).The 5-year and 10-year OS were significantly higher for patients who obtained a pCR compared with patients who do not achieve it .The 5-year and 10-year DFS were both 94% for patients who obtained pCR, and 69.4% and 68.1% for patients with partial response (p < 0.001).The 5-year and 10-year MFS were both 94% for patients who obtained pCR, 74.5% and 73% for patients with partial response (p = 0.02).No local recurrence was registered for patients who obtained a pCR. The 5-year and 10-year LC in patients who did not achieve pCR was 90.6% and 89% respectively (p = 0.07). In patients who underwent surgery with an interval time of ≤8 weeks, 5-year and 10-year OS was 80.7% and 69.8%, respectively, compared with 84.5% and 78% in patients with an interval time of >8 weeks (p = 0.05). The 5-year and 10-year DFS were 72% and 69% in the ≤8 weeks group and both 77% in the >8 weeks group (p = 0.2).Survival outcomes were analyzed for each study group. According to the concurrent chemotherapy schedule, the 5-year and 10-year OS was 77% and 65% for the 1-drug group, and 86% and 77.2% for the 2-drug group . The increased interval may potentially increase the tumor downstaging as the radiation-induced necrosis appears to be a time-dependent effect.Usually, surgical resection is performed after 6–8 weeks from the end of preoperative CRT based on the findings of the Lyons R90-01 trial . In our p = 0.001) without increasing postoperative complication rates [These results agree with the findings of several other retrospective series that showed how a higher rate of pCR and better oncological outcomes with fewer postoperative complications are associated to a longer time interval between CRT and surgery ,26,27,28on rates .p = 0.05) and interval time to surgery (p = 0.002) were significant, and the resting time of >8 weeks was confirmed at multivariate analysis (p = 0.003).Moreover, in our study, a correlation between an increased resting time and the pathological response to CRT was also observed. The downstaging rate was 81.6% in the group with the interval time to surgery of >8 weeks and 65% in the group with time to surgery ≤8 weeks. At univariate analysis for downstaging, only age , there was no difference between the two groups: 14.4% (18/125 patients vs. 14.8% (19/128 patients) in the 7-week and 11-week groups, respectively, and the only two patients with grade V toxicity were in the 7-week group . In addition, anastomotic leakage was more frequent in the 7-week group compared with the 11-week group: 15.9% vs. 14%. The pCR rate for the delayed surgery group was 17.4% compared with 15% of the 7-week group—a difference not statistically significant .In our experience, the delayed surgical approach did not increase the risk of surgical complications. Overall, acute postoperative complications rates were similar for patients with an interval time to surgery of ≤8 weeks and patients with an interval time to surgery of >8 weeks: 46% and 42% respectively.Similarly, Garcia-Aguilar et al. in a phase II study on 259 patients, extended considerably the resting time between CRT and surgery by administering two, four or six cycles of chemotherapy after CRT. They did not observe increased complications or technical difficulties, reporting higher pCR rates with an increased waiting time after CRT: 18% in the control group, 25% after 2 cycles of chemotherapy, 30% after 4 cycles and 38% after 6 cycles .p = 0.05). The 5-year and 10-year DFS were 72% and 69% in the ≤8 weeks group, and 77% in the >8 weeks group (p = 0.2).In our study, in patients who underwent surgery with an interval time of ≤8 weeks, 5-year and 10-year OS were 80.7% and 69.8%, compared with 84.5% and 78% in patients with an interval time of >8 weeks . Grade 2 and grade 3 acute hematological toxicity occurred in 19 patients (13.1%) who received 1-drug chemotherapy during radiotherapy and in 54 patients (43.2%) who received 2-drug chemotherapy. Grade 2 and grade 3 gastrointestinal toxicity rate was 20.1% in the first group and 40.8% in the second group. In our study, the addition of oxaliplatin during preoperative radiotherapy resulted in a higher toxicity rate in the absence of clinical benefits.In this study, chemotherapy was administered concurrently with radiotherapy in all patients and consisted of 5-FU or CAPE in 144 patients (53.5%), and 5-FU or CAPE plus oxaliplatin in 125 patients (46.5%). The pCR rate was similar in both groups (26.5% vs. 25.6% p = 0.904). Grade 3–4 adverse events during CRT were higher in the 2-drug group  [Similar results have been reported in several randomized trials. Among these, in the STAR-01 phase III trial, 747 patients with LARC were randomly assigned to receive pelvic radiation and concomitant 5-FU alone or in association with oxaliplatin. The rate of pCR was 16% in both arms (= 0.001) .p < 0.0001) [Allegra et al. randomized 1608 patients affected by LARC to receive 5-FU or CAPE during CRT with or without oxaliplatin. No statistically significant differences were found in terms of DFS, LC and OS between the groups. Moreover, the addition of oxaliplatin did not reduce local recurrence even in the highest-risk patient population, whereas grade 3–4 diarrhea was statistically significantly higher in patients who received oxaliplatin ( 0.0001) .p = 0.09), nor did the rate of complete and near complete response (p = 0.008) [In the ACCORD 12 trial, 598 patients were randomly assigned to receive capecitabine or capecitabine plus oxaliplatin concurrently with preoperative radiotherapy. The rate of pCR did not differ significantly (= 0.008) .The addition of oxaliplatin during radiotherapy is currently being investigated in several ongoing clinical trials ,36. DataThe main limitation of this study is the retrospective design, while the strengths of the study are the homogeneity of the population in terms of staging and treatments and the long period of follow-up.In conclusion, in our cohort, an interval time from CRT to surgery of >8 weeks is the only significant factor for pCR and downstaging.The findings of this study may be useful for data collection and for encouraging the development of future trials that could help to better clarify how radiotherapy can further improve clinical outcomes in LARC patients.


Background and objectiveThe term asymptomatic bacteriuria (ASB) refers to the isolation of bacteria in a urine specimen of individuals without any symptoms of urinary tract infection (UTI). Diabetes mellitus (DM) is a disease involving multiple organ systems, characterized by its chronicity and hence endless complications including ASB. This study aimed to determine the characteristics of ASB and antibiotic susceptibility patterns among patients with diabetes.Materials and methodsThis was a retrospective observational study conducted in a tertiary care hospital. The study included patients with a diagnosis of diabetes with no signs and symptoms of UTI but who still showed the growth of an organism in urine culture. A total of 222 urine cultures were analyzed retrospectively, ensuring that they met the inclusion criteria through non-probability consecutive sampling.ResultsThe mean age of the study participants was 62.89 ± 13.77 years; 76% of them were females, and 61% had a family history of diabetes. The most frequent organisms isolated were Escherichia coli (E. coli), Enterococcus, Klebsiella pneumonia, Pseudomonas aeruginosa, and Enterobacter species. A total of 20 subjects had dual bacterial growth in their cultures, with Enterococcus species (n=17) being the most common organism. Gender, family history of diabetes, levels of hemoglobin A1c (HbA1c), and advanced age were all found significantly associated with ASB.ConclusionOur study is the first of its kind to analyze and examine the risk factors associated with ASB in DM patients, and to identify the pathogens involved, along with assessing their antibiotic resistance profiles. Diabetes mellitus (DM) is a disease involving multiple organ systems. Its hallmark is its chronicity, and hence it is associated with endless complications that occur due to a defect in the production or utilization of insulin, a hormone that helps to regulate blood sugar levels by transporting glucose to different tissues for uptake when the glucose levels in the blood reach above a standard level of concentration -3. AccorASB is defined as the existence of bacteria in the urine of a patient who has not shown any symptoms or signs of a UTI . It is dDiabetic patients with ASB often tend to experience pyelonephritis and albuminuria . PreviouOnce diagnosed with DM, patients require lifelong insulin therapy or adjunctive therapy with this hormone to control glycemic levels . Adequathttp://www.raosoft.com/samplesize.html), from a total population size of 500, response distribution (anticipated frequency of outcome factor in the population) of 50%, confidence interval of 95%, and margin of error of 0.05. ASB is diagnosed either based on the presence of 100,000 colony-forming units (CFU)/ml in a midstream clean catch urine sample or on the presence of 100 CFU/ml in the urine sample obtained from a catheterized patient [This was a retrospective observational study conducted at the internal medicine department of a tertiary care hospital. The medical records of all patients were accessed after obtaining ethical approval from the institutional review board. A sample size of 218 was calculated by using the Raosoft sample size calculator , age (in years), gender, family history of DM, and comorbidities including hypertension, chronic kidney disease (CKD), and others, while the second section was further divided into two sub-sections. The first sub-section included the space to document signs and symptoms of UTI (any patient with features of UTI was not included in the study). The second sub-section included the level of hemoglobin A1c (HbA1c), gram staining, and a list of organisms causing UTIs and antibiotics that are usually used to treat it. The documented urine cultures of the study population having positive bacterial growth were included. All those patients who were diagnosed with DM and were not having any signs and symptoms of UTI at the time of admission but had a positive urinary culture were included in our study. All those patients who did not have DM, those who had signs and symptoms of UTI, or those having negative urinary culture were excluded from the study. The study also excluded all symptomatic UTI patients, pregnant females, and all those who used antimicrobial medications in the last two weeks prior to the study.After the data was collected through the non-probability consecutive sampling method. It was analyzed on IBM SPSS Statistics version 25.0  and results were obtained. The statistical difference was calculated via independent sample t-test, chi-square test, and Fisher’s exact test. A p-value of <0.05 was considered statistically significant.Out of the 222 included subjects, there were three times as many women as men, and they had a slightly younger mean age of 61.54 ± 13.86 years as compared to men (p=0.007). Two-thirds of the study subjects with a positive urinary culture were in the age group of 50-75 years. Around 58% of males had a family history of DM, in contrast with 62% of females; 28.37% of females had a known history of CKD in contrast with 9% among males; 36% of females had hypertension while only 14.28% among males had it. Ischemic heart disease was found in 4.95% of females and 4.50% of males. Almost 40% of the subjects had HbA1c in the range of 6.5-9.0%, 22% had it in the range of 5.7-6.5%, and the remaining percentage segments of the subjects had it equally distributed in the ranges of <5.7%, 9-11.5%, 11.6-14.0%, and >14.0% respectively . Patients diagnosed with other organisms did not have a family history of diabetes. Out of the 20 subjects who had a dual growth in their cultures, 13 had a positive family history of DM  was found most sensitive to amikacin (84.49%) followed by fosfomycin (80.62%) and gentamicin (66.67%). It was found resistant to ampicillin (86.04%) followed by cefixime (82.94%) and cefuroxime (82.17%). Among the 27 positive cultures of Klebsiella pneumonia, the most sensitive antibiotic was fosfomycin (70.37%) followed by amikacin 55.56%) and piperacillin/tazobactam (44.44%); they were found to be resistant to ceftriaxone (77.78%), cefixime (77.78%), and cefuroxime (74.07%) respectively. Pseudomonas was positive in 10 cultures; it was most sensitive to ciprofloxacin (70%) followed by ceftazidime (60%) and amikacin (60%), while being most resistant to ceftazidime (40%), as shown in Table 5.56% andAmong the patients with CKD (n=83), Enterococcus was the most likely organism to be positive in urine culture, with 57.8% being infected (n=26), while the rest  infecting non-CKD patients (p=0.002). While E. coli was positive in only 35 CKD patients (27.1%), the rest of 94 cultures (62.9%) were found in non-CKD patients (p=0.0002). Enterobacter was exclusively present in the cultures of patients with CKD, with all the nine growths (100%), as opposed to no growth in non-CKD patients (p=0.0001). With respect to patients presenting with no other comorbidities except for DM (n=96), E. coli was the most likely associated organism (n=52) with a p-value of 0.001, while Enterococcus was more likely to occur in patients with multiple comorbidities (p=0.010). With respect to patients with benign prostatic hyperplasia (BPH) (n=22), E. coli was found infecting 50% of their cultures (n=11), among others (p=0.561).Many studies have investigated the risk factors associated with ASB in DM patients; however, few such studies have been conducted in Pakistan. It is important to identify the risk factors associated with ASB in diabetic patients, considering how the prevalence of DM is increasing in the Pakistani population and how ASB in patients with their associated comorbidities can lead to adverse outcomes. This study aimed to outline the associated risk factors of ASB in DM, the pathogens involved, and their antibiotic sensitivity profiles. The risk factors for ASB include proteinuria/albuminuria, raised creatinine levels, female gender, elevated HbA1c, longer duration of diabetes, prior UTI history, overuse of antibiotics, and use of sodium-glucose cotransporter-2 (SGLT2) inhibitors.Various studies have shown demographic factors  to be associated with ASB in DM patients. Our study validates those findings with results showing that the mean age of our patients was high (62.89 ± 13.77 years), which was similar to the mean ages reported by Turan et al. (60.8 ± 9.5 years), Geerlings et al. (63.0 ± 10 years), and Odetoyin et al. (65.52 ± 9.4 years) ,15-16. TAnother significant demographic factor that should be considered is the female gender; 76.1% of our study population were women. Various studies have confirmed the role of the female sex as a risk factor for ASB in diabetics, and our results fell along these lines. These results are strikingly similar to those reported by Turan et al., where 77.2% of females were positive for ASB  . StudiesThe role of glycemic control (HbA1c) as a risk factor for diabetic patients to develop ASB has been controversial. Studies in the literature are both for and against its role as a risk factor. Our results show a significant association between the HbA1c levels and the risk of diabetic patients developing ASB. Around 89 (40.1%) of our subjects had an HbA1c between 6.5-9.0%. The overall mean HbA1c of the subjects was 8.46 ± 2.64%. Turan et al. have confirmed in their study that poor glycemic control is a risk factor for ASB . The meaThe most common comorbidity  in our study was CKD, which was present in 37.38% of our population. Zhanel et al. reported that 5.9% of their patients had kidney disease, which is much lower than our findings . The higOur study found three organisms to be the most common among patients with ASB, namely E. coli (53.3%), Enterococcus (18.6%), and Klebsiella pneumonia (11.15%). Multiple studies have reported a variety of pathogens in their results. A study that is very much in line with our findings was conducted in Sudan, which also found E. coli (56.4%), Klebsiella pneumonia (23.0%), and Enterococcus faecalis (12.8%) to be the most common organisms . A studyWe found that E. coli was mainly susceptible to aminoglycosides and fosfomycin, with resistance shown predominantly to ampicillin and third-generation cephalosporins. Nigussie et al. found that E. coli was sensitive to nitrofurantoin (100%), norfloxacin (90.9%), ciprofloxacin (81.8%), but resistant to ampicillin (100%) and trimethoprim-sulfamethoxazole (81.8%) . This stKlebsiella pneumonia was susceptible to fosfomycin (70.37%) followed by amikacin (55.56%) and piperacillin/tazobactam (44.44%) while showing resistance mostly to cephalosporins and lower resistance to amoxicillin. A study in China showed that Klebsiella pneumonia was resistant to amoxicillin (100%), cephalothin (50%), and cefuroxime (41.7%) . AlebiosThe most sensitive antibiotics for Enterococcus were fosfomycin (71.1%), amoxicillin (46.67%), and vancomycin (40%). Enterococcus showed resistance mainly to levofloxacin (57.78%) and ampicillin (44.44%). He et al. showed that Enterococcus in their studies was resistant to levofloxacin as well (33.3%), but the resistance to the antibiotic seen in our study was greater . Hamdan This study has a few limitations. The study was conducted at a single tertiary care hospital in an urban location. Moreover, the aspects of sexual hygiene, socioeconomic status, urinary catheterization, other risk factors for ASB, and the duration of diabetes were not taken into account in our analysis.Despite many studies present in the literature about ASB in DM patients, with diverse protocols and study populations, data regarding the risk factors of ASB in DM patients in Pakistan is scarce. In this regard, our study is the first of its kind to analyze and study the risk factors associated with ASB in DM patients, and to identify the pathogens involved, along with assessing their antibiotic resistance profiles. Based on our results, we recommend that more similar studies be conducted in the region, to improve and develop guidelines and protocols on managing patients with ASB and DM. Based on the limited data that we obtained from our study, we would recommend that doctors or nephrologists plan to start antibiotics prophylactically with caution because of a high prevalence of resistance to antibiotics. Hence, we recommend that antibiotics be used prophylactically only if the patient has two or more comorbidities, in order to prevent the complications that can be caused by ASB, such as pyelonephritis, perinephric abscess, and renal scarring.


Coinfections with other respiratory viruses were detected in 51% of the hBoV-positive patients. Significant differences in the prevalence of hBoVs were found during the different study periods and in patients of different age groups. The detection rate of hBoV was the highest in patients aged 0–4 years (6.9%). In this age group, hBoV was the only identified virus in 9.7%, 5.8%, and 1.1% of the children diagnosed with laryngotracheitis, bronchiolitis, and pneumonia, respectively. Among patients aged ≥5 years, hBoV was detected as a single agent in 2.2% of cases of pneumonia. Phylogenetic analysis showed that all Bulgarian hBoV strains belonged to the hBoV1 genotype. A few amino acid substitutions were identified compared to the St1 prototype strain. This first study amongst an all-age population in Bulgaria showed a significant rate of hBoV detection in some serious respiratory illnesses in early childhood, year-to-year changes in the hBoV prevalence, and low genetic variability in the circulating strains.Нuman bocaviruses (hBoVs) are often associated with acute respiratory infections (ARIs). Information on the distribution and molecular epidemiology of hBoVs in Bulgaria is currently limited. The objectives of this study were to investigate the prevalence and genetic characteristics of hBoVs detected in patients with ARIs in Bulgaria. From October 2016 to September 2019, nasopharyngeal/oropharyngeal swabs were prospectively collected from 1842 patients of all ages and tested for 12 common respiratory viruses using a real-time RT-PCR. Phylogenetic and amino acid analyses of the hBoV VP1/VP2 gene/protein were performed. HBoV was identified in 98 (5.3%) patients and was the 6 Bocaparvovirus . T. T17]. TPartial VP1/VP2 gene nucleotide sequences of hBoV strains analyzed in this study were deposited in GenBank under the accession numbers MW759050-MW759067.https://blast.ncbi.nlm.nih.gov/Blast.cgi). The sequences obtained in the present study were aligned with the published sequences using the MUSCLE program embedded in Molecular Evolutionary Genetics Analysis software . The best fit nucleotide substitution model, Tamura-3 parameter (T-92 + G), was determined using MEGA 6.06. A phylogenetic tree based on the VP1/VP2 gene was constructed using the maximum likelihood method within MEGA 6.06 software. The reliability of the tree topology was evaluated by bootstrapping with 1000 replications. The study strains were genotyped based on clustering with sequences representing known genotypes.The VP1/VP2 gene nucleotide sequences of representative strains of all known hBoV genotypes as well as sequences of human and animal parvoviruses were downloaded from GenBank using the Basic Local Alignment Search Tool (BLAST)  to identify the sequence motif N-X-S/T (sequon), where X can be any amino acid except proline. Only the sites with scores higher than 0.5 were accepted as glycosylated.Putative N-glycosylation sites were predicted using the NetNGlyc 1.0 web server . Chi-square and Fisher's exact tests were used for analyzing the following categorical variables: patients' age, sex, clinical features of illness, and incidence of each virus. A p value of <0.05 was considered to be statistically significant.Statistical analyses were performed using GraphPad Prism This study was conducted from October 2016 to September 2019 and included three influenza seasons, each starting with week 40 of one year and ending with week 20 of the following year. A total of 1842 patients exhibiting symptoms of ARI were enrolled in the study: 498 in the first season, 500 in the second season, 743 in the third season, and 101 between seasons. Twelve percent (225/1842) of these patients attended outpatient healthcare centres, and 87.8% (1617/1842) were hospitalized. The patients' ages ranged from 10 days to 91 years (median age 4.2 years). In the target population, 1332 (72.3%) were 0–4 years old, 170 (9.2%) were 5–17 years old, 75 (4.1%) were 18–64 years old, and 265 (14.4%) were ≥65 years old. A total of 1007 (54.7%) of the patients were males, and 835 (45.3%) were females.th most frequent virus among the respiratory viruses tested, following RSV (20.4%), influenza A(H1N1)pdm09 (11.1%), influenza A(H3N2) (10.5%), RV (9.9%), and AdV (6.7%)  (130 outpatients and 1099 inpatients) of them were positive for at least one of these pathogens. Monoinfections were detected in 1042 (56.6%) patients; 172 (9.3%) patients were coinfected with two viruses; and 15 (0.8%) were coinfected with 3 viruses. HBoV was identified in 98 (5.3%) of the examined patients and was the 6V (6.7%) .p=0.24) , 9.6% (48/500), and 3.8% (28/743), respectively, and in the periods between seasons, it was an average of 8.9% (9/101). The incidence rates of hBoV infection among the outpatients and inpatients were 4% (9/225) and 5.5% (89/1617), respectively, with no statistically significant difference (p=0.24) .n = 17), followed by RSV (n = 11), AdV (n = 5), influenza A(H1N1)pdm09 (n = 4) and A(H3N2) (n = 3), PIV1 (n = 2), PIV3 (n = 2), and HMPV (n = 1). There were no cases of coinfections with PIV-2 and influenza type B. Codetection of two or three different viruses in the same clinical sample was found in 45 (45.9%) and 5 (5.1%) hBoV-positive patients, respectively. Among the respiratory viruses studied, AdVs, hBoVs, and RVs were characterized by the highest proportion of coinfections: 58.1%, 51%, and 41.2%, respectively  of the hBoV-positive patients were coinfected with one or two additional respiratory viruses. The most frequently identified copathogens were RVs . HBoV was detected in few or no specimens in the summer months, but the number of samples tested during this period was relatively small. The highest number of hBoVs was identified in specimens obtained in November 2017  and December 2018  . The perp < 0.05). In the age group of 5–17 years, three of the hBoV-positive patients were 5 years old and two were 6 years old. Among the patients ≥65 years of age, the only hBoV-positive patient was an 82-year-old man with serious breathing difficulties (emphysema). Coinfections of hBoV were detected only in children aged 0–4 years. Of the 98 hBoV-positive patients, 60 (61.2%) were males and 38 (38.8%) were females without a statistically significant difference (p = 0.21).Viral respiratory infections were detected in 73.9% of patients aged 0–4 years, 57.2% of patients aged 5–17 years, 29.3% of patients aged 18–64 years, and 46.4% of patients aged ≥65 years. HBoV detection varied in patients aged between 3 months and 82 years. The incidence of hBoV infection was the highest among the youngest age group (0–4 years) (6.9%) and the lowest among the ≥65 years age group (0.4%). No hBoVs were detected in patients aged 18–64 years . ChildreThe contribution of hBoV and other tested respiratory viruses to the development of certain clinical syndromes, laryngotracheitis, bronchiolitis, pneumonia, and central nervous system (CNS) involvement , was analyzed. A total of 113, 346, 186, and 43 cases of laryngotracheitis, bronchiolitis, pneumonia, and CNS complications were diagnosed among the children aged 0–4 years, respectively. The hBoV was the second most commonly detected virus in patients with the diagnosis of laryngotracheitis , third in patients with the diagnosis of bronchiolitis , and sixth in patients with the diagnosis of pneumonia . The incidence of the hBoV as a single agent in children diagnosed with laryngotracheitis, bronchiolitis, and pneumonia was 9.7%, 5.8%, and 1.1%, respectively. Among the patients aged ≥5 years, hBoV alone was identified in 2.2% (2/91) of the cases of pneumonia . No hBoVFor phylogenetic analysis, a fragment of the VP1/VP2 gene from 18 hBoV-positive clinical specimens was sequenced. The remaining positive samples had poor or failed PCR amplification or sequencing, probably due to the greater sensitivity of real-time PCR compared to conventional PCR for genotyping or due to low viral load in some samples. The hBoV sequences were obtained from hospitalized children aged 3 months–6 years with lower respiratory tract infections and from different regions of the country. Phylogenetic analysis showed that all hBoV strains isolated in this study belonged to the hBoV1 genotype and hBoV2–4 were not detected. The Bulgarian strains were grouped with the original strain St1 (GenBank access number DQ000495), identified by Allander et al. in 2005 . The hBoThe deduced amino acid sequences of 18 Bulgarian hBoVs were aligned and compared with the sequence of the prototype strain St1 . In the p < 0.05). Annual variations in the incidence of hBoV have also been observed in other countries [This study presents the prevalence and genetic characteristics of hBoVs amongst an all-age population in Bulgaria over three consecutive seasons, as well as the epidemiological and clinical features of hBoV respiratory tract infections. HBoV showed a moderate detection rate and was the 6th most prevalent virus among the tested 12 respiratory viruses. The general positive rate of hBoV was 5.3%, with a significant difference between seasons: 2.4%; 9.6%; and 3.8%  were also screened. A high rate of hBoV coinfections has been also found in studies in other countries: 75% (Spain) ; 78.1% . The other three genotypes hBoV2–4 were not found, although some authors reported a low frequency of detection of these genotypes in respiratory samples , 40. HBoThis first study amongst an all-age population in Bulgaria showed a significant frequency of hBoV detection in some serious respiratory illnesses in early childhood, year-to-year changes in the hBoV prevalence, and low genetic variability in the circulating strains. Our results could suggest a pathogenic role of this virus in cases of ARI, but additional methods  should be included to confirm the causality. Viremia, detection of HBoV1 IgM, and seroconversion of IgG antibodies have been considered by some researchers as diagnostic markers for acute hBoV1-induced respiratory illness . Prolong


Objective: Appropriate use of oral anticoagulants (OACs) reduces the risk of stroke in patients with atrial fibrillation (AF). The study characterized the prescribing of OACs in people with AF in the Australian primary care setting over 10 years.Design: Retrospective population study.Setting and Participants: We performed 10 sequential cross-sectional analyses of patients with a recorded diagnosis of AF between 2009 and 2018 using national general practice data. The proportion of patients with AF who were prescribed an OAC based on their stroke risk was examined.Primary and secondary outcomes: The primary outcome was the proportion of high stroke risk patients who were prescribed an OAC over a decade. The secondary outcome was variation in OAC prescribing among general practices.Results: The sample size of patients with AF ranged from 9,874 in 2009 to 41,751 in 2018. The proportion who were prescribed an OAC increased from 39.5% (95% CI 38.6–40.5%) in 2009 to 52.0% (95% CI 51.5–52.4%) in 2018 (p for trend < 0.001). During this time, the proportion of patients with AF and high stroke risk who were prescribed an OAC rose from 41.7% (95% CI 40.7–42.8%) to 55.2%  with the direct-acting oral anticoagulants accounting for over three-quarters of usage by 2018. There was substantial variation in OAC prescribing between general practices. In 2018, the proportion of moderate to high stroke risk patients who were prescribed an OAC was 38.6% (95% CI 37.2–40.1%) in the lowest practice site quintiles and 65.6% (95% CI 64.5–66.7%) in the highest practice site quintiles.Conclusions: Over the 10 years, OAC prescribing in high stroke risk patients with AF increased by one-third. There was considerable variation in OAC prescribing between general practices. Appropriate utilization of oral anticoagulants reduces stroke risk in patients with atrial fibrillation . The vitRecent studies on the utilization of OAC have highlighted both underuse and overuse in patients with AF in Australia . The TasThe primary objective of this study was to investigate the proportion of Australian primary care patients with AF prescribed an OAC according to their stroke risk, and temporal trends in prescribing patterns over a 10 year period. The secondary objective was to examine variation in OAC prescribing between general practices.Data for this study was obtained from NPS MedicineWise’s dataset, MedicineInsight. This is the largest and the most representative  general practice dataset available to researchers in Australia . A totalMedicineInsight uses a third-party tool that extracts, de-identifies and securely transmits patient data each week to its secure data repository. The extraction tool allows developing a longitudinal database of patients in general practices. The data that MedicineInsight collects from general practices include patient demographics, diagnoses, pathology test results, prescribed medications, and reasons for encounter. However, specific patient identifiers, such as patient name, address, and date of birth, are not included in this dataset .We performed 10 sequential cross-sectional analyses of data on 1 September every year (census date) from September 01, 2009 to September 01, 2018. Patients with a recorded diagnosis of non-valvular AF were included in each analysis if 1) they were aged 18 years or older and not deceased on or before the census date, 2) they had had three or more recorded general practice visits in the previous two years and at least one of these visits was in the last six months, and 2) they had been registered in the general practice’s electronic records at least one year before the census date. We excluded patient who had a recorded OAC prescription before the diagnosis of AF. We defined patients with AF as being prescribed an OAC  or antiplatelet agent  when they had at least one recorded prescription, dated within 365 days before the census date. The prescriptions recorded in this dataset were only those prescribed by general practitioners (GPs). Aspirin is available without a prescription, but we could only capture prescribed data.2DS2-VASc score (congestive heart failure (1 point), hypertension (1 point), age ≥75 years (2 points), diabetes mellitus (1 point), stroke/transient ischaemic attack (TIA) (2 points), vascular disease (1 point), age 65–74 years (1 point) and sex female (1 point)) for assessing stroke risk and treatment eligibility in patients with AF  or low stroke risk  who were prescribed an OAC was calculated each year for each practice site. Potentially appropriate prescribing was defined as prescribing of an OAC to patients with a medium to high stroke risk. Potentially inappropriate prescribing was defined as prescribing an OAC to patients with low stroke risk. All practice sites that contributed data at least for a year were included. Prescribing rates were ranked into quintiles and used as an indicator of general practice sites’ prescribing performance. The variation between the highest- and lowest-prescribing practice quintiles each year was calculated as a prescribing gap. We calculated linear-weighted kappa coefficients for ordered categories to determine whether practice performance remained constant over the study period  quintile is an index developed by the Australian Bureau of Statistics (ABS) and ranks areas in Australia from 1 (most disadvantaged area) to 5 (most advantaged area) . The ABSEthics approval was obtained from the Tasmanian Health and Medical Human Research Ethics Committee (H0017648). We also obtained approval to conduct this study from MedicineInsight’s independent Data Governance Committee (2018–033). Patients were not identifiable, and individual patient consent was waived for our ethics application.No patient involved.p for trend < 0.001). The proportion of male patients increased from 51.4% (95% CI 50.4–52.4%) in 2009 to 54.5% (95% CI 54.0–55.0%) in 2018  of patients with AF increased slightly from 75.1 (11.6) years in 2009 to 76.0 (11.6) years in 2018  in 2009 to 35.1% (95% CI 34.5–35.8%) in 2011 and then increased to 52.0% (95% CI 51.5–52.4%) by 2018 (2DS2-VASc≥2), the proportion with an OAC prescription recorded increased from 41.7% (95% CI 40.7–42.8%) in 2009 to 55.2% (95% CI 54.7–55.8%) in 2018 (p < 0.001). In moderate stroke risk patients , the proportion who were receiving an OAC increased from 30.9% (95% CI 27.2–34.7%) in 2009 to 42.0% (95% CI 40.2–43.8%) in 2018 (p < 0.001). In low stroke risk patients with AF , the proportion who were prescribed an OAC decreased from 14.6% (95% CI 11.8–17.8%) in 2009 to 11.0% (95% CI 9.6–12.6%) in 2013 and then increased to 16.7% (95% CI 15.3–18.2%) in 2018  with AF and an OAC prescription recorded among the lowest prescribing practice quintile was 24.7% (95% CI 22.3–27.4%), compared with 54.7% (95% CI 52.6–56.9%) in the highest quintile. By 2018, prescribing had increased to 38.6% (95% CI 37.2–40.1%) and 65.6% (95% CI 64.5–66.7%) in the lowest and highest practice quintiles, respectively. The gap between the highest- and lowest-prescribing practice quintiles in OAC prescribing for patients with moderate to high stroke risk remained wide, falling slightly from 30.0% in 2009 to 25.9% in 2018  had provided data since 2009, of which 64 (37.9%) of practice sites’ OAC prescribing quintile did not change, and 120 (71.0%) practice sites continued in the same or closest prescribing quintile. There was reasonable agreement in practices sites’ prescribing quintile between 2009 and 2018, weighted kappa = 0.34 (95% CI 0.24–0.45) .2DS2-VASc = 0 and male or CHA2DS2-VASc = 1 and female) in the lowest- and highest-prescribing quintiles were 5.7% (95% CI 3.7–8.4%) and 39.3% (95% CI 31.3–47.8%), respectively. At the end of the study period, the proportion of potentially inappropriate prescribing in the lowest- and highest-prescribing quintiles had increased to 6.7% (95% CI 5.5–8.0%) and 47.1% (95% CI 41.9–52.4%), respectively  in 2011 to 76.3% (95% CI 75.7–76.8%) in 2018, while the proportion of those prescribed warfarin correspondingly decreased from 97.3% (95% CI 96.8%97.7%) to 23.8% (95% CI 23.2–24.3%) .2DS2-VASc score ≥1) instead of antiplatelet therapy  . In 2010 therapy . This wa therapy . These c therapy . Similar therapy .In 2018, just over half of the high-risk patients were prescribed an OAC. This rate is low compared with the rates reported from previous studies. The Tasmanian AF study found 63% of high-risk patients were prescribed an OAC. However, that study involved hospitalized patients who might have been more comorbid than general practice patients and it excluded patients with known OAC contraindications. A study in the United Kingdom using general practice data found that over three-quarters of high-risk patients with AF were prescribed an OAC . Another2DS2-VASc scores. A study by Yoon et al.  and potentially inappropriate (for low stroke risk) prescribing. One possible reason for the observed gaps in the appropriate use of an OAC might be the absence of regular reassessment of CHAn et al.  found thThis was the first AF study conducted using MedicineInsight dataset, which provided a large and national study population and thus enabled a comprehensive description of GP prescribing of OACs in Australia . FurtherThe study has several limitations. The MedicineInsight dataset contains only records of medications prescribed by GPs. However, GPs in Australia typically continue those medications prescribed by cardiologists and so the trends described in this study may still be considered accurate and useful with regard to overall OAC prescribing. We did not account for medication contraindications and adverse drug reactions, that may have prevented GPs from prescribing an OAC.In this study, we used the guidelines retrospectively. For instance, before 2012, OAC treatment was recommended for patients at moderate to high stroke risk, and aspirin was widely used for patients at low stroke risk . HoweverOver the 10 years, overall OAC prescribing increased by one-third. By 2018, 55.2% of the patients with a high stroke risk had an OAC prescription recorded, with the proportion varying substantially between practices. There remains scope to improve OAC prescribing for AF in the primary care setting, and the reasons for withholding OAC therapy in eligible patients need to be investigated.


Viburnum genus is of particular interest to horticulturalists, phylogeneticists, and biogeographers. Despite its popularity, there are few existing molecular markers to investigate genetic diversity in this large genus, which includes over 160 species. There are also few polymorphic molecular tools that can delineate closely related species within the genus. Viburnum farreri, a member of the Solenotinus subclade and one of the centers of diversity for Viburnum, was selected for DNA sequencing and development of genomic simple sequence repeats (gSSRs). In this study, 15 polymorphic gSSRs were developed and characterized for a collection of 19 V. farreri samples. Number of alleles per locus ranged from two- to- eight and nine loci had four or more alleles. Observed heterozygosity ranged from 0 to 0.84 and expected heterozygosity ranged from 0.10 to 0.80 for the 15 loci. Shannon diversity index values across these loci ranged from 0.21 to 1.62. The markers developed in this study add to the existing molecular toolkit for the genus and will be used in future studies investigating cross-transferability, genetic variation, and species and cultivar delimitation in the Viburnum genus and closely allied genera in the Adoxaceae and Caprifoliaceae.The  Viburnum L.  includeoliaceae  that areoliaceae ,4. Majoroliaceae ,6,7,8. Stivation . In 2017tivation . In addivolution ,12,13,14volution ,17,18,19Viburnum .Viburnum farreri Stearn, fragrant viburnum, is classified within the clade Crenotinus and the subclade Solenotinus n as the most common di-nucleotide repeat and [GC]n being the least common n wt common ,46. Primo = 0.23) varied greatly from the expected heterozygosity (He = 0.60), and this result may be explained by the cultivated origin of most of the samples. The Shannon Diversity Index was very low (1.10) and indicated low allele species richness/evenness, which could be caused by the limited number of samples used in this dataset. These initial values of basic diversity measures are included as an illustration and possible point of reference for future in-depth studies of this (or related) species.Sixty-seven alleles were detected with the 15 gSSRs and loci yielded two- to- eight alleles per locus with an average of 4.47 alleles per locus . SelecteV. farreri genome because most pairs of loci did not have a high Linkage disequilibrium among loci was investigated using the standardized index of association  . The miSeq raw reads are available at NCBI Bioproject PRJNA706016. Read quality was assessed with FastQC version 0.11.7  before aV. farreri gDNA samples. The reaction volume was 10 µL and included 5 µL of 2× AccuStart II PCR SuperMix , 3 µL autoclaved water, 1 µL of mixture of 5 µM forward and reverse primers, and 1 µL of 2 ng/µL of gDNA. The PCR thermal profile included 3 min of initial denaturation at 94 °C, 10 touchdown [Viburnum samples and two primer pairs were eliminated from the study because of low and/or inconsistent amplification. The allele sizes were determined using QIAxcel ScreenGel version 1.6.0.10. Raw allele sizes were then statistically binned into allelic classes with FlexiBin (an Excel macro) [Twenty di-, 15 tri-, and 15 tetra-nucleotide primer pairs  were selected randomly from outputs of the Perl script for screening Primers were synthesized by Integrated DNA Technologies . PCR was conducted with all 50 primer pairs on three randomly selected ouchdown  cycles (l macro) .poppr version 2.8.6 [poppr and hierfstat version 0.5–7 [poppr was also used in calculations to test if pairs of loci were in linkage disequilibrium. Calculations were performed with the standardized index of association (A) [All data analyses were performed in R version 4.0.3 . The binon 2.8.6 . The twoon 0.5–7 . The pacion (IA) .V. farreri in this study are likely distributed throughout the genome, are polymorphic, and thus informative, and useful for estimating genetic diversity. The polymorphic loci will be beneficial in more advanced studies of V. farreri and informative in cross-transfer studies involving many Viburnum species across all clades as well as closely related genera.The 15 gSSR markers developed from


The effect of PM2.5 or PM10 on asthma hospitalizations were 4.67%  and 4.04% , respectively (p < 0.05). The 65+ years age group had a higher risk associated with PM2.5 and PM10 exposure and hospital admissions for all respiratory diseases on the same day . Compared to the lower ambient air pollution period, higher increased hospital admissions were observed among those aged above 65 years, males, and COPD and pneumonia hospital admissions during the high ambient air pollution period. Active efforts are crucial to improve ambient air quality in this region to reduce the health effects.Evidence of associations between exposure to ambient air pollution and health outcomes are sparse in the South Asian region due to limited air pollution exposure and quality health data. This study investigated the potential impacts of ambient particulate matter (PM) on respiratory disease hospitalization in Kandy, Sri Lanka for the year 2019. The Generalized Additive Model (GAM) was applied to estimate the short-term effect of ambient PM on respiratory disease hospitalization. As the second analysis, respiratory disease hospitalizations during two distinct air pollution periods were analyzed. Each 10 μg/m Respiratory diseases are among the major causes of death and disability globally. Approximately 65 million people suffer from chronic obstructive pulmonary disease (COPD), of whom 3 million die each year, making COPD the third leading cause of death worldwide . Asthma The association between ambient air pollution exposure and respiratory outcomes has been examined in many previous studies in terms of daily mortality, emergency department visits, and hospital admissions ,6. Among10) at twenty sites in the Kandy region, it was found that the mean 24-h PM10 concentration was 129 µg/m3 (range: 55–221 µg/m3), which is well above the World Health Organization (WHO) air quality guideline [2.5 and PM10 concentrations in Kandy are high and exceed WHO guidelines [Ambient air pollution is a growing problem in Sri Lanka and the neighboring countries, mainly due to the exponential growth in motor vehicles. In many developing countries, ambient air pollution is a neglected public health issue. It has been identified that the air quality in Kandy, the second largest city in Sri Lanka, is high compared to the capital Colombo . This maidelines .2.5 and PM10 on the risk of daily hospital admissions for respiratory diseases in Kandy area using the hospital admission data from the two major hospitals in 2019.The lack of evidence on the associations between exposure to ambient air pollution and health outcomes in the Kandy area is a significant knowledge gap that limits effective public health interventions. Therefore, in this study, we aimed to estimate the short-term effects of PM2, with a total population of approximately 1.5 million. The City of Kandy is the capital of the province and it is situated in a low valley surrounded by mountain ranges. It has a resident population of approximately 120,000 [The Kandy District in the Central Province of Sri Lanka has a land area of 1917 km 120,000 . The two2.5 and PM10) were obtained from a validated small sensor unit established in a central location of Kandy city, Knowing Our Ambient Local Air-quality (KOALA). These KOALA monitors were developed by the International Laboratory for Air Quality and Health (ILAQH) at the Queensland University of Technology (QUT), Brisbane, Australia. This sensor continuously measured PM2.5 and PM10 using light scattering technology. Detailed information on sensor performance and validation has been published elsewhere [2.5 and PM10 measurements and meteorological measurements of temperature (°C) and relative humidity were obtained for the period 1 January 2019 to 31 December 2019.Ambient air quality data  were obtained from 1 January 2019 to 31 December 2019. The data included date of admission, age, gender and the principal disease diagnosis coded according to the International Classification of Diseases, 10th revision (ICD-10). Hospitalization for respiratory diseases (ICD-10: J00–J99): pneumonia (ICD-10: J18), asthma ((ICD-10: 45) and chronic obstructive pulmonary disease  were included in the study. Further, we conducted an age- (≤64 years and 65+ years) and gender-stratified analysis for the association between PM exposure and respiratory disease hospital admissions.2.5, PM10) and respiratory diseases hospitalization [A Generalized Additive Model (GAM) was applied to estimate the association between ambient air pollution .E(Yt) represents the expected number of respiratory disease hospitalizations on day t; α denotes the intercept; S is the spline smoothing function for the variables of time, temperature and humidity; df is the degrees of freedom; β denotes the coefficient for air pollutants; and Zt denotes the concentration of air pollutant on day t. To investigate the delayed effects of air pollutants on respiratory diseases hospitalization, we used day lags of PM2.5. The high air pollution period was defined as when the daily average PM2.5 levels were greater than the WHO guideline (25 µg/m3). In contrast, the low air pollution period was defined as the period where the low levels of average PM2.5 were below the WHO guideline. We modeled the associations between respiratory disease hospitalization in the high pollution period by selecting three representative months for both high (1 March 2019 to 31 May 2019) and low ambient air pollution (1 August 2019 to 31 October 2019) and compared the periods using the low pollution period as the reference. Assuming that the change in the baseline population within six months is negligible, we used rate ratios (RRs), defined as the ratio of the number of hospitalizations in the high ambient air pollution period and the reference period. Then, 95% confidence intervals were obtained using the following formula, where a and b are the number of hospitalizations in the high and low periods [We also identified two distinct seasons of ambient air pollution in 2019, based on the measured average PM periods :(1)exp. Associations of a 10 µg/m3 increment in PM2.5 and percent changes of all respiratory disease hospitalizations were found at lag0 with 1.95% , PM10 at lag0 with 1.63% . In this analysis, we have investigated lag effects for more than a month for both pollutants. However, significant associations were found at lag0 and lag1. Therefore, we have presented the results only up to lag5.Results of the PM3 increase in pollutants are reported in 2.5 and PM10 in males. At lag0, a 10 µg/m3 increase in PM2.5 exposure was associated with increased respiratory disease hospitalization in both males and females . The 65+ years age group had a higher risk associated with both PM2.5 and PM10 exposure and hospital admissions for all respiratory diseases . Estimated effects of PM2.5 and PM10 exposure on ≤65 years group were not significant at lag0. However, both pollutants’ 10 µg/m3 increase showed associations at lag1, with increased respiratory diseases of 2.23% and 1.93%. For both pollutants, the largest percent increase values occurred at the current day 10 µg/m3 increase in PM2.5 or PM10 on asthma hospitalizations  (p < 0.05). The association between increased concentration of PM2.5 and PM10 and hospitalization for pneumonia and COPD was not statistically significant at any of the lags  and PM10  were approximately two times higher compared to the low air pollution period. For our analysis, we selected three representative months of high air pollution (1 March 2019 to 31 May 2019) and three representative months of low air pollution (1 August 2019 to 31 October 2019) as the reference period. The number of respiratory disease cases referred to the two hospitals were 2427 and 2946 during low and high air pollution periods, respectively. The gender distribution of hospitalizations for the period was 23.49% and 30.30% for males during low and high air pollution periods, respectively, and 21.68% and 24.53% for females during low and high air pollution periods, respectively. Notably, 9.77% and 13.16% of respiratory disease hospitalization were due to COPD during the low and high air pollution periods, respectively (As shown in ectively .p < 0.0001), male respiratory diseases , female respiratory diseases , both age groups  and COPD   .Compared to the low air pollution reference period, increased hospital admissions were observed for all respiratory diseases during the high air pollution period ). During the high air pollution period, increased respiratory disease hospital admissions were observed among elders (65+ years) ) compared to ≤ 65 year olds ), compared with the low air pollution period. Similar associations were observed for COPD ) and pneumonia ) during the high air pollution period compared with the low air pollution period . In addi2.5 and PM10 levels and increased risk of respiratory disease hospital admissions. A 10 µg/m3 increase in PM2.5 and PM10 were associated with an increased risk of respiratory disease hospitalization by up to 1.95 % and 1.63%, respectively, on the same day. Moreover, those aged above 65 were more vulnerable to PM2.5 and PM10 exposure. Furthermore, our analysis reported significant effects of short term PM2.5 and/or PM10 exposure on asthma hospitalizations. In our analysis comparing respiratory disease hospital admissions in high and low air pollution periods, we identified a statistically significant increase in hospital admissions for all respiratory diseases, in males, and for COPD and pneumonia during the high air pollution period.The present study showed significant associations between PM3 increment in PM2.5 on the current day was associated with a 2.0% increase in overall respiratory disease hospitalization, which is in line with most previous studies. A study in Eastern China found that an increase of 10 µg/m3 in PM2.5 corresponded to a 1.4%  increase in respiratory emergency room visits in urban areas, and a 1.5%  rise for the suburban population. In the same study, short term PM10 exposure was linked with an increase of 1.63% at lag0 for all respiratory disease hospital admissions per 10μg/m3 increase in PM10 concentration [3 increase of PM10 was associated with a 2.20% rise in hospital admissions for respiratory diseases [Our findings showed that a 10 µg/mntration . A studydiseases .2.5 on hospital admission at lag0 were observed in both females and males (2.35% (95% CI: 0.08–4.68 %) and 2.24% (95% CI: 0.08–4.44%), respectively). Older people had higher respiratory disease hospital admissions, with percent changes of 2.74% and 2.28% in those aged above 65 years at lag0 due to a 10 μg/m3 rise of PM2.5 and PM10, respectively. Many of the previous studies have identified older adults as a high-risk group for air pollution exposure [3 increment in PM2.5 and PM10 on the previous day, respiratory disease hospitalization in those aged less than 65 years also showed statistically significant increases of 2.23% and 1.93%, respectively, while for the current-day exposure, results were statistically insignificant. In line with previous studies, we observed a strong significant association between short-term PM2.5 and/or PM10 exposure and asthma hospitalization [2.5 exposure and COPD hospitalization found that a 10-µg/m3 increase in PM2.5 at lag 0–7 days could lead to a 3.1% (1.6–4.6%) increase in COPD hospitalization [In our gender-stratified analysis, significant effects of PMexposure . For a 1lization ,28. Perclization . Howeverlization .During the high air pollution period a high-rate ratio was observed for male respiratory disease hospitalization compared to female respiratory disease hospitalization. We can speculate the reason for this finding might be males spending more time outside during the high air pollution period  because of their employment and social factors . Our ageThe two distinct air pollution periods observed in Kandy were demarcated by patterns of rainfall, with high rainfall generally starting after April . Regiona2.5 and PM10 data and meteorological factors in this study were obtained from one fixed air quality monitoring sensor unit in Kandy, which may not represent the population’s total exposure. Therefore, our study might underestimate the effects of PM2.5 and PM10 on respiratory disease hospitalization. However, we analyzed air pollution data from the network of four units of KOALA, covering a large part of Kandy, that was taken from February to March in 2020. According to the average value of the daily mean level of PM2.5 and PM10 and their lower standard deviations of each of these four KOALA units, the pollution was generally uniformly distributed around the city. Therefore, we are confident that this result may be applied to the actual period of monitoring and that we can safely use the results from our monitoring to represent the average concentrations in the Kandy region.  exceeded the Sri Lankan standards. More significantly, the measurements from Kandy are often found to be higher than the corresponding values of Colombo [In 2018, the majority of hourly average PM Colombo . This hi2.5 and PM10 on respiratory disease hospitalization identified significant positive associations between PM2.5 and PM10 concentration at different lag days and hospitalization for respiratory diseases. Higher hospital admissions for respiratory diseases were observed during the high ambient air pollution period compared with the low ambient air pollution period. Our analysis suggests that males and older people are more vulnerable to respiratory disease hospitalization during high ambient air pollution period. To our knowledge, this is the first study to estimate PM and respiratory hospital admissions using continuous air pollution measurements in Sri Lanka. Overall, in the region, air pollution monitoring and quality hospital admission data are limited. Therefore, this study provides evidence that applications of low-cost air pollution measurements to investigate health risks associated with PM air pollution can be adopted by such low-resource settings. Furthermore, our findings highlight the importance of regular widespread air pollution monitoring and identify the need for immediate actions and regulatory measures to reduce PM air pollution levels, which will in turn lead to reduced respiratory disease hospital admissions.Our investigations of the short-term effects of PM


The Will Rogers phenomenon [WRP] describes an apparent improvement in outcome for patients’ group due to tumor grade reclassification. Staging of cancers is important to select appropriate treatment and to estimate prognosis. The WRP has been described as one of the most important biases limiting the use of historical cohorts when comparing survival or treatment. The main purpose of this study is to assess whether the WRP exists with the move from the AJCC 7th to AJCC 8th edition in breast cancer [BC] staging, and if racial differences are manifested in the expression of the WRP.This is a retrospective analysis of 300 BC women (2007–2017) at an academic medical center. Overall survival [OS] and disease-free survival [DFS] was estimated by Kaplan-Meier analysis. Bi and multi-variate Cox regression analyses was used to identify racial factors associated with outcomes.p = 0.043). In prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011).Our patient cohort included 30.3% Caucasians [Whites] and 69.7% African-Americans [Blacks]. Stages I, II, III, and IV were 46.2, 26.3, 23.1, and 4.4% of Whites; 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in anatomic staging  Blacks, upstaged. Whites (16.49% vs. 14.35%) Blacks, downstaged. The remaining, 38.46 and 37.79% patients had their stages unchanged.p = 0.000). Among the Whites, those who were stage IIIA in the 7th but became stage IB in the 8th had a better prognosis than stages IIA and IIB in the 8th (p = 0.000). The 8th showed complex results (p = 0.176) compared to DFS estimated using the 7th edition (p = 0.004).With a median follow-up of 54 months, the Black patients showed better stage-by-stage 5-year OS rates using 8th edition compared to the 7th edition (The WRP exists with significant variability in the move from the AJCC 7th to the 8th edition in BC staging (both White and Black patients). We suggest that caution needs to be exercised when results are compared across staging systems to account for the WRP in the interpretation of the data. Breast cancer is the most frequently diagnosed cancer in the world and the second leading cause of death in females . AfricanBreast cancer has been staged using AJCC TNM staging based on anatomic factors like the extent of the primary tumor (T), the status of adjacent nodes (N), and the presence of distant metastasis (M) . HoweverThe Will Rogers phenomenon is an epidemiological paradox named after the remark made by the humorist Will Rogers about migration during the American economic depression of the 1930’s. Later in 1935, Alvan Feinstein proposed the name “Will Rogers phenomenon” to describe the effect of the “stage migration” in cancer patients where the stage-specific survival improved compared to an earlier cohort, even though the outcome of individual patients has not changed . In oncoOver the past decades, the scientific developments led to a better understanding of breast cancer according to the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation marker Ki-67)  or African Americans [Blacks]) and ductal carcinoma in situ were excluded from the study. A total of 300 breast cancer women were included in this analysis , tumor grade, receptors  status and survival months. Patients were then restaged using the 8th AJCC prognostic staging system to estimate the effect of stage migration  on the stage specific survival compared to the earlier cohort. All data was collected, checked, analyzed, and interpreted by the postdoc research fellow (MN).The Will Rogers phenomenon refers to the “improved” survival of patients with cancer or other diseases by either reclassifying them into different prognostic groups, recognizing subtle disease manifestations, or by using diagnostic modalities that allow the disease to be diagnosed at an earlier stage. Disease-free survival (DFS) is defined as the number that predicts the chances of staying free of disease or cancer after a particular treatment. Overall survival (OS) is defined by the number of days from the date of initial diagnosis until the date of death/ the last contact. The censored cases defined as the patients without death at the time of the last follow up.p-values were recorded. Kaplan-Meier method was used to estimate the OS rates and the univariate significance of differences among survival curves calculated by the Mantel-Cox log-rank test. The five-year OS rates by AJCC stage group and race were estimated from the cumulative proportion surviving at the particular time . P values ≤0.05 were considered significant. To indicate Will Rogers phenomenon, the improved survival by stage in AJCC 8th edition vs. AJCC 7th edition is recorded. The co-variables associated with the OS and DFS were determined by the bi and multivariate Cox regression model. The Black race is considered the referent group for the analyses. Hazards ratio (HR) was used to estimate time to event outcome with associated 95% confidence intervals (CIs) and P values ≤0.05 were considered statistically significant. Data was analyzed using SPSS 24.0 software .The Pearson’s chi-square test was used to discover the relationship between the two categorical variables as well as the stage migration changes between the two races. The respective p = 0.025). Black breast cancer women presented were with higher BMI levels compared to Whites .A total of 300 primary breast cancer patients treated at UMMC between 2007 and 2017 were identified. Out of 300 patients, 91 (30.3%) were Whites and 209 (69.7%) Blacks. The baseline characteristics of these patients (Table p = 0.336). The Blacks were significantly less likely to have positive tumor receptors of ER (65.6% vs. 74.7%) and PR (48.3% vs. 64.8%) compared to White women. Stages I, II, III, and IV accounted for 46.2, 26.3, 23.1, and 4.4% of Whites and 28.7, 43.1, 24.4, and 3.8% of Blacks respectively, in 7th AJCC anatomic staging (p = 0.043). In 8th AJCC prognostic staging, 52.8, 18.7, 23, and 5.5% were Whites while 35, 17.2, 43.5, and 4.3% were Blacks, respectively (p = 0.011). Black women were significantly more likely to be diagnosed at a later stage, notably at stage IIB and higher in 7th AJCC anatomic staging and notably at stage IIIA and higher in 8th AJCC prognostic staging.When the receptor characteristics of this study population were measured, the most common subtype was ER+/PR+/HER2-, accounting 33.3% of Whites and 66.7% of Blacks, respectively (P = 0.859)  upstaged compared to 100 Black (47.9%) patients. Fifteen White patients (16.5%) and 30 Black patients (14.4%) were downstaged. Of the remainder, 35 White (38.5%) and 79 Black (37.8%) patients had their stages unchanged (9) Table . The grep = 0.000). Univariate analysis by Kaplan-Meier demonstrated that White patients with stage IIIA had a worse prognosis than those with stage IIIB within the 7th AJCC anatomic staging system  at a median follow-up of 58 months (range 4 to 235 months) . For Black patients, stage IIIA, IIIB, IIIC, and IV  all demonstrated better prognoses in the 8th edition when compared to the 7th edition (p = 0.000).The five-year OS rates by stage Table  indicatep = 0.176) compared to DFS estimated using the 7th’s anatomic staging system (p = 0.004)  Table . For Whi4) Table  Table 3p = 0.176p = 0.046) compared to White patients.The hazard ratios [HR] comparing racial differences (Blacks vs. Whites) about the risk of death was calculated by bivariate Cox regression Table . The Blap = 0.002), IIB , and IIIA . Followed by increased risk of death for stages IIIB , IIIC , and three times significantly higher risk of death for stage IV , compared to the White breast cancer patients.The risk estimates for 7th AJCC staging indicate that Black breast cancer patients showed significant decreased risk for stage IIA , IIA ; decreased risk for stage IIB  and stage IIIB . Showed increased risk of death for stages IIIA , stage IIIC , and twice significantly higher risk of death for stage IV , compared to the White breast cancer patients.The risk estimates for 8th AJCC staging indicate that Black breast cancer patients showed significant decreased risk for stage IB , IIIA , and three times significantly higher risk of death for stage IV , compared to the White breast cancer patients , and IIIB  showed significantly decreased risk.All the stages in the 8th AJCC staging group showed decreased risk for Black patients compared to Whites. Stage IB , IIA , demonstrating that upstaging reports more accurate disease outcomes and suggested to re-evaluate the nodal involvement impact upon new staging system . It is vp < 0.001) over the past two decades improving the clinical outcomes  reflecting the Will Rogers phenomenon . Many factors contribute to race-related disparities in breast cancer outcomes , 18; tumThe poorer prognosis for obese Black patients has been reported in a previous study ; our stuBlack women were less likely to have positive hormone receptors (ER/PR/HER2), more likely to have negative hormone receptors, and significant racial differences were noted in histologic categories , our stuIn our study, 5-year OS rates by stage indicate that for White breast cancer patients, IIIC was still inferior to stage IV in the 7th AJCC staging system but this inconsistency was reproduced at IIIB and IV in the 8th AJCC prognostic staging system. Among the Black breast cancer patients, IIA was inferior to stage IIB in the 7th AJCC staging system with no inconsistency (IIA & IIB) but inconsistent (IIB & IIIA) in the 8th AJCC prognostic system. Stage IIIA among White patients in the 7th AJCC migrated to IB and have a worse prognosis than IIA or IIB in the 8th AJCC prognostic system. In contrast, IIIA patients among Black patients had better survival than IIA or IIB in the 8th AJCC prognostic system. A similar inconsistency was observed in the 5-year DFS between both races when restaged from 7th AJCC to 8th AJCC.Our analyses suggest that the Will Rogers phenomenon exists in the move from the AJCC 7th to the 8th edition in breast cancer staging in both White and Black patients. However, there were significant variabilities between the races in the extent of their manifestation. We suggest that caution needs to be exercised when results are compared across staging systems in view of the Will Rogers Phenomenon in the interpretation of the data for both Caucasians and African Americans.