Taenia solium porcine cysticercosis (PCC) and gastrointestinal (GI) parasites co-infection status in pigs. One hundred sixty-one households were selected randomly and visited between November and December 2019. A household questionnaire was administered, and faecal and blood samples were collected from at least one pig older than 3 months per household. A blood sample was obtained from a jugular venipuncture, and a rectal faecal sample was obtained. Taenia spp. circulating antigen levels in the sample sera were tested using a commercial enzyme-linked immunosorbent assay kit, apDia™ cysticercosis Ag ELISA. The modified McMaster technique was used to identify and quantify the GI parasites. The apparent animal-level seroprevalence for PCC was 4.8% (95% CI 2.7–7.1) and differed across the two districts (p = 0.018). At the pig herd level, the prevalence was 9.7% (95% CI 5.5–14.4). The prevalence of the different nematode eggs and coccidian oocysts in the two districts was as follows: strongyles 79.0% (95% CI 74.3–83.6), coccidia 73.3% (95% CI 68.3–78.6), Trichuris spp. 7.4% (95% CI 4.9–10.6), Strongyloides ransomi 2.1 (95% CI 0.7–3.5) and Ascaris spp. 4.9 (95% CI 2.8–7.4). Overall, across the two districts, the arithmetic mean for the oocysts per gram (OPG) for coccidia was 2042.2 ± 5776.1, and eggs per gram (EPG) were the highest in strongyles 616.1 ± 991. Overall, 57.4% of the porcine cysticercosis seropositive pigs were also positive for at least one of the gastrointestinal helminths which included strongyles, Strongyloides ransomi, Trichuris spp. and Ascaris spp. The co-infection status of pigs with both PCC and GI parasites demonstrated by this study can provide an incentive for integrating the control and management of both parasites with oxfendazole. Further studies are required to understand the feasibility of using oxfendazole including cost–benefit analysis and the acceptability by local stakeholders for the control of T. solium cysticercosis and gastrointestinal parasites in pigs.A study was carried out in Kamuli and Hoima districts in Eastern and Western regions of Uganda to determine the The online version contains supplementary material available at 10.1007/s00436-021-07380-9. In Uganda, the production and consumption of livestock and livestock products have been growing rapidly, with the greatest growth observed in the pig sector (Twine and Njehu Taenia (T.) solium cysticercosis, gastrointestinal parasites and African Swine fever (ASF) pose a significant risk to the growth of the sector and negatively impact on pig and human health , Trichuris spp. and coccidia  to estimate the prevalence of PCC, gastrointestinal parasites and the level of co-infection in pigs, (ii) to assess the risk factors associated with the infection with PCC (iii) and to provide the evidence base to support integrated control of pig gastrointestinal parasites as an integral aspect of T. solium cysticercosis control.The control of both 2 of the total area of 241,551 km2  led by Uganda Pig Genetics project (UPG), which formed the basis for entry to the study sites for the current study. The districts have also been a focus for ILRI’s research on smallholder pig value chain, and the initial selection has been described elsewhere  at a probability level of 0.05; P is the estimated prevalence of 25.7%; q is (1 − P) that is the probability of having no disease; and d is the desired precision level (5%). This formula gives a sample size of n = 293 pigs as the minimum. For gastrointestinal parasites, the same formula as above is used, and the expected prevalence of 61%  to the household head, spouse or the person familiar with the running of the pig enterprise. Data were collected on self-reported and observational variables: pig confinement (during the rainy and dry season and during the day and night); pig water source during the dry and wet season; self-reported pig health management practices including deworming; pork slaughter and consumption practices; household hygiene and deworming practices; knowledge on https://play.google.com/store/apps/details?id = ru.uxapps.random&hl = en&gl = US).Sensitization meetings were conducted at the village level a week prior to start of the survey. During the sensitization meeting, the project team introduced the project, and written informed consent was obtained from the farmers. During the household visits, pigs that were 3 months or older, not pregnant, not lactating and not manifesting overt clinical signs were sampled up to a maximum of 3 pigs per herd. If the farm had more than 3 eligible pigs, a serial number was allocated to the pigs, and 3 pigs were selected using random numbers generated by a random number generator app running on a mobile device  at Makerere University in Kampala for processing and analysis within 24 h after collection. Serum samples were stored temporarily in the field at − 20 °C and transported to CDL after 2 weeks for analysis.Taenia spp. circulating antigen in porcine sera was tested using a commercial enzyme-linked immunosorbent assay kit, apDia cysticercosis Ag ELISA . The filtrate was stirred with a Pasteur pipette, and a sub-sample was picked while stirring and transferred to the first chamber of the McMaster slide while ensuring no air bubbles were left on the slide. While still stirring, the other chamber of the slide was filled, and the McMaster slide was left to stand for 5–10 min to allow the eggs to float. The McMaster slide was examined using the compound microscope at 10 × 10 magnification, and the eggs within each grid were identified and counted. To get the total number of each type of worm eggs, the number obtained per species was multiplied by 50 to obtain the eggs per gram (EPG) and oocysts per gram (OPG) for coccidia. The results were recorded in Microsoft Excel version 2016. The method used has an estimated sensitivity of 66.67% and specificity of 81.06%  were constructed in Dagitty online platform  with village as a random effect. All tests for significance were performed at the α = 0.05 level, and odds ratios (OR) and 95% confidence intervals (CI) were determined. The models were built by first having a global model with all potential predictors identified through the univariable modelling. The final model was then selected automatically based on information theory using the dredge function in MuMIn package in R (Barto The association of predictor variables and PCC seropositivity (negative/positive) was tested at the household level using univariable logistic regression. The models were not built at the individual level because only two variables were measured at the animal level, age and weight and they were highly correlated. Predictors with  R Barto . This meDemographic characteristics of the study population, pig husbandry practices and household hygienic practices are summarized in Tables p < 0.05, Fisher’s test).The different levels of confinement level of the different pig age categories in the two districts are presented in Table Sweet potato vines were a commonly used pig feed in both Kamuli and Hoima districts Table . The comThe majority of the surveyed households reported consuming pork either at home (88.20%) or in pork joints  83.85%). Two thirds of people in both districts were aware of human tapeworm infestation, just a half of them had heard of pork cysts or pork measles, and only a handful (6.8%) knew that pigs could get the cysts by eating human faeces. Further, 6.8% and 14.3% of people reported that pigs could acquire cysts from drinking dirty water or from eating contaminated feed, respectively. Only 20% of people in Kamuli had dewormed compared to 45.5% in Hoima, however, only 6.1% of Hoima respondents could remember the date of these last deworming compared to 57.7% of Kamuli residents. However, a large proportion of children had been dewormed under the government mass drug administration (MDA) programs in schools, 58.8% in Kamuli and 92.7% in Hoima district. Among the surveyed households in Hoima and Kamuli district 10.3% and 25.8%, respectively, boiled drinking water. In Kamuli district, 96.2% got drinking water from a public shallow well as compared to 72.3% of the households in Hoima district . There was no significant difference in exposure to PCC between sex, age and breed of the animal . Household-level seroprevalence was 9.7% (95% CI 5.5–14.4) which significantly differed across the study districts 3.8% (1.2–8.2) for Kamuli and 16.6% (9.0–25.6) for Hoima .The prevalence of PCC was calculated at both individual and household levels. The apparent individual level seroprevalence was 4.8% (95% CI 2.7–7.1) .A total of 281 pig faecal samples were examined of which 91.8% (95% CI 88.9–94.9) were positive for GI parasite infections. The arithmetic mean for the oocysts per gram for coccidia was 2418 ± 1078 in Kamuli and 1647 ± 5540 in Hoima district, eggs per gram was highest in strongyles 684 ± 1078 and 544 ± 889 in Kamuli and Hoima districts, respectively, followed by Trichuris spp. 7.4% (95% CI 4.9–10.6), Strongyloides spp. 2.1% (95% CI 0.7–3.5) and Ascaris spp. 4.9% (95% CI 2.8–7.4) .The prevalence of the different parasite eggs was as follows: strongyles 79.0% 95% CI 74.3–83.6), coccidia 73.3% (95% CI 68.3–78.6), .3–83.6, Strongyloides spp., Trichuris spp. and Ascaris spp. excluding coccidia The co-infection proportion was highest for PCC + strongyles (57.1%). The prevalence of co-infection with any GI parasite and PCC was found to be 3.0% (95% CI 1.3–4.8). The co-infection of pigs with any GI parasite and PCC significantly differed across the two districts. Hoima district had more pigs infected by both PCC and gastrointestinal parasites . There was no difference in PCC/GI parasite co-infection by sex, breed and age of pig .Overall, 57.4% of the proportion of PCC positive pigs were also positive for any of the gastrointestinal parasites, including strongyles, p < 0.1 (Table p < 0.05) of household-level seroprevalence of PCC with district and the knowledge that pigs can get infected with PCC by consuming dirty feed at univariate level analysis (Table p = 0.005), OR 5.5 (95% CI 0.7–43.8)  Table .Table 5RSeveral other studies reporting prevalence and risk factors of PCC and GI parasites separately exist for different parts of Uganda. However, to the best of our knowledge, this is the first study to report the co-infection of pigs with GI parasites and PCC to guide integrated control of both parasites. The overall apparent prevalence of PCC across the two districts (Kamuli and Hoima) was found to be 4.8% (95% CI 2.7–7.1) at the individual level and 9.7% (95% CI 5.5–14.4) at the household level. The individual level prevalence is similar to that reported by Kungu et al.  for ruraT. hydatigena in the current study, recent studies have reported no co-infection of pigs with T. solium and T. hydatigena  has not been studied in Uganda. Therefore, the possibility of cross-reactivity cannot be completely ruled out.Although no carcass dissection was conducted as recommended by Lightowlers et al.  to rule n = 63) by HP10 Ag ELISA. The sensitivity of this method is 89.5% and specificity of 74% . The drivers for the fluctuation in the prevalence rates between the 2005 study and the current study is not yet known. However, we may hypothesize this marked reduction in prevalence between the two studies could be attributed to the ongoing improvements in the pig husbandry practices, increased latrine coverage across Kamuli or adoption of MDA programs targeting neglected tropical diseases (NTDs). This finding is supported by a report of Uganda’s Ministry of Health documenting that MDA programs are annually conducted in Kamuli and Hoima districts using praziquantel to control schistosomiasis (bilharzia)  MoH . PraziquIn 2005, Waiswa et al.  reportedAdditionally, there could be differential latrine coverage across different geographical locations within the districts especially along the water bodies like Lake Albert in Hoima district and along River Nile in Kamuli district. These places are prone to flooding, and toilet construction may be challenging. Nsadha et al.  noted arDistrict was a significant predictor of PCC seropositivity in the univariable analysis. The prevalence of open defecation may differ between districts, possibly because Hoima district has large areas covered with dense vegetation that may suggest ‘adequate privacy’ for open defecation. It is less so in Kamuli district. Similar observations have been made in Nigeria Abubakar  and TanzT. solium transmission would have a protective effect on seropositivity. Still, the variable appears to be a risk factor in our analysis. This relationship’s theoretical basis is unclear and may need further investigation, although we acknowledge that the association may be a statistical artefact. Other studies have found that knowledge of the transmission cycle was associated with reduced risk of the disease but not knowledge on the risk of feeding contaminated feeds  for the two districts. Kamuli district had 93.0 (95% CI 89.5–97.0) and Hoima district 90.5 (95% CI 86.1–95.0). The most prevalent infection was strongyles at 79.0% (74.3–83.6). Similar infection levels have been reported in different regions of Uganda  and Trichuris suis (264) than the current study. Similar intensities of parasite infections have also been reported by Lagu et al. . Nissen et al.  in a stuu et al.  and Waisu et al. . There w Ózsvári . AlthougT. solium cysticercosis. In the current study, 95% of farmers dewormed pigs mainly using albendazole, findings similar to results by Dione et al.  is of significance to report in the current study. It presents an opportunity to use integrated approaches to control both parasites. Farmers in Uganda recognize infection with worms as a major constraint to pig production .This study provides data on the current epidemiological status of PCC and pig GI parasites in Kamuli and Hoima districts, Uganda. Our findings demonstrate that Supplementary file1 (DOCX 16 KB)Below is the link to the electronic supplementary material.


Disease-specific mortality of acute lymphoblastic leukemia (ALL) increases with age. So far, only a few analyses have investigated disease characteristics of elderly patients (>55 years) with newly diagnosed ALL. The aim of our retrospective study was to evaluate the treatment results of 93 elderly patients who received intensive chemotherapy between May 2003 and October 2020. We identify poor performance status and older age at the time of diagnosis as risk factors for inferior outcomes, while ALL immunophenotype, BCR::ABL1 status, the complexity of karyotype, and intensity of treatment did not significantly affect overall survival (OS). With 17.3% of patients dying while in complete remission (CR), an event-free survival (EFS) and OS of 32.9% and 47.3% at 3 years, our data suggest that intensive treatment of elderly ALL patients is feasible but associated with significant toxicity. These results underline the need for novel, less toxic treatment approaches for this vulnerable cohort of patients.n = 88) or T-ALL (n = 5), who received age-adapted, pediatric-inspired chemotherapy regimens at our center between May 2003 and October 2020. The median age at diagnosis was 65.7 years, and surviving patients had a median follow-up of 3.7 years. CR after induction therapy was documented in 76.5%, while the rate of treatment-related death within 100 days was 6.4%. The OS of the entire cohort at 1 and 3 year(s) was 75.2% (95% CI: 66.4–84.0%) and 47.3% (95% CI: 36.8–57.7%), respectively, while the EFS at 1 and 3 years(s) was 59.0% (95% CI: 48.9–69.0%) and 32.9% (95% CI: 23.0–42.8%), respectively. At 3 years, the cumulative incidence (CI) of relapse was 48.3% (95% CI: 38.9–59.9%), and the CI rate of death in CR was 17.3% (95% CI: 10.9–27.5%). Older age and an ECOG > 2 represented risk factors for inferior OS, while BCR::ABL1 status, immunophenotype, and intensity of chemotherapy did not significantly affect OS. We conclude that intensive treatment is feasible in selected elderly ALL patients, but high rates of relapse and death in CR underline the need for novel therapeutic strategies.Prognosis of elderly ALL patients remains dismal. Here, we retrospectively analyzed the course of 93 patients > 55 years with B-precursor ( Although significant treatment advances in pediatric and young adult patients with acute lymphoblastic leukemia (ALL) have been achieved over the last decades, the outcome for elderly ALL patients (commonly defined as older than 55–60 years of age) remains dismal ,9,10,11.Elderly ALL patients represent a heterogeneous group regarding performance status, medical history, and comorbidities and thus largely differ in treatment tolerability . In manyCompared to younger patients, elderly ALL patients present with specific features of ALL biology, including higher proportions of B-ALL immunophenotype, positivity for the BCR::ABL1 transcript, complex karyotype, TP53 mutations, and therapy-related disease ,16,17,18Due to the high rate of substantial comorbidities, previous reports estimated that less than 50% of elderly ALL patients received intensive chemotherapy with curative intent . In GermHere we provide detailed data on disease characteristics, course of treatment, prevalence of risk factors, and outcome of a single-center cohort of 93 B-precursor or T-ALL patients > 55 years receiving age-adjusted intensive chemotherapy regimens.We retrospectively analyzed data by reviewing patient records from 106 consecutive patients (pts) treated for precursor ALL at the University Hospital Muenster, Germany, between May 2003 and October 2020. The Charlson Comorbidity Index (CCI)  and the The primary endpoints analyzed in this study were OS and EFS calculated from the day of the first diagnosis. EFS was defined as survival without relapse or progressive disease—the latter referring to patients with primary refractory ALL. For a subgroup analysis of patients receiving an allogeneic HSCT, the day of transplantation was defined as day 0 for calculation of OS and RFS after transplant. OS was defined as survival until death from any cause or time of final follow-up, as of 24 June 2021. RFS was defined as survival without relapse for patients who achieved a complete remission . Secondary endpoints were cumulative incidence of relapse (CIR) and non-relapse mortality (NRM). CIR was defined as time to leukemic recurrence after achieving complete remission. NRM was defined as death in continuous remission, i.e., death from any other cause than relapse or refractory disease and without the occurrence of a previous relapse. The term NRM, when used with a percentage, referred to the number of non-relapse deaths over the number of patients in the sample evaluated. OS, EFS, and RFS were analyzed using the Kaplan-Meier method. Cumulative incidence curves were used to estimate CIR and NRM. Patients with primary refractory disease were excluded from the calculation of cumulative incidences. Results are shown, including the 95% confidence interval.p < 0.2 in univariate analysis were included in multivariate analyses (metric variables utilized as continuous parameters), performed using the Cox proportional hazards model. Statistical analyses were performed with the IBM SPSS statistics version 27  and XLSTAT 2016 .Univariate analyses were performed using the log-rank-test for EFS and OS, Cox proportional hazards model for OS, and Gray’s test for cumulative incidences. For descriptive statistics, Pearson’s Chi-squared test for categorical and Wilcoxon’s rank sum test for continuous variables were utilized. Variables with a ALL patients treated within the INITIAL-1 study Among the remaining 93 intensively treated patients aged >55 years with precursor ALL, 88 patients were diagnosed with B-ALL and 5 patients with T-ALL . SeventyOut of the 93 patients, eighty-four (87.5%) were admitted to our center to receive first-line induction chemotherapy. Of these, eight patients (8.3%) were referred for salvage treatment and four patients (4.1%) for allogeneic HSCT. Patients were treated according to the respectively valid recommendations of the GMALL study group.The median patient age at diagnosis was 65.7 years (ranging from 55.2–85.1 years) . 45.8% oOf all patients, 10.7% presented with therapy-related ALL after cytotoxic treatment of a primary malignancy (4 pts with prior breast cancer). In addition, 3 patients had prior malignancy ALL (pm-ALL) treated with surgery only.26.7% of the patients had one or more risk factors such as hyperleukocytosis or pro-B-ALL phenotype . 14.1% op = 0.005)  . Apart fThe median follow-up of all patients was 2.2 years (range 24 days–16.9 years), and the median follow-up of surviving patients was 3.7 years (range 8.8 months–16.9 years), respectively.For intensive chemotherapy, age-adapted pediatric-inspired treatment regimens, according to the recommendations of the GMALL for younger  or elderly patients , were applied . PatientIn general, the treatment regimens consisted of two cycles of induction therapy followed by consolidation, reinduction, and consolidation therapy cycles in the 1st year and consecutive maintenance therapy in the 2nd year of treatment. The induction regimen and the reinduction cycle administered after the 2nd cycle of consolidation therapy included dexamethasone, cyclophosphamide, vincristine, idarubicin, and cytarabine combined with intrathecal (i.th.) CNS prophylaxis . Consolidation consisted of alternating cycles of high-dose methotrexate/asparaginase and high-dose cytarabine, as well as i.th. CNS prophylaxis. Additionally, rituximab was administered depending on the treatment regimen: to patients with BCR::ABL1 negative B-precursor ALL and >20% CD20+ blasts (if treated according to the recommendations for elderly patients) as well as to all BCR::ABL1 negative and those BCR::ABL1 positive patients with >20% CD20+ blasts. Nonetheless, these recommendations were not consistently followed throughout the study period, as rituximab was also frequently administered to patients with <20% CD20+ blasts.All 27 patients with a BCR::ABL1 transcript received first-line treatment with the tyrosine kinase inhibitor (TKI) imatinib, either in addition to conventional induction chemotherapy (according to the recommendations for younger ALL patients) or as monotherapy in induction therapy (according to the recommendations for elderly ALL patients) . RemissiOf all patients in our cohort, 89.7% received i.th. therapy, 24.4% underwent prophylactic cranial irradiation, and 4.4% received involved site irradiation .The CR rate after induction therapy was 76.5% among those patients receiving their initial induction therapy at our center . MRD staThe rate of early death after intensive therapy (within 100 days after the start of treatment) was 6.4%, and 24.7% of the patients died within one year after diagnosis . The 3 pIn both BCR::ABL1 positive and BCR::ABL1 negative patients, no significant differences in outcome could be detected for patients receiving more or less intensive chemotherapy , application of i.th. therapy, or irradiation .OS of the entire cohort at 1 and 3 year(s) was 75.2% (95% CI: 66.4–84.0%) and 47.3% (95% CI: 36.8–57.7%), respectively a. EFS atThe cumulative incidence of relapse at 1 and 3 year(s) was 26.0% (95% CI: 18.4–36.8%) and 48.3% (95% CI: 38.9–59.9%), respectively c, with aOf note, 14 of the 45 patients with relapsed B-precursor ALL received salvage treatment, including blinatumomab and/or inotuzumab ozogamicin. The most frequent salvage treatment applied other than blinatumomab and/or inotuzumab ozogamicin was fludarabine/cytarabine/idarubicine (12 pts), and 7 of the patients receiving blinatumomab and/or inotuzumab ozogamicin salvage therapy subsequently underwent allogeneic HSCT.p < 0.001), whereas patients aged 55–65 years and 66–75 years had comparable outcomes . Comparing an ECOG of 0–1 vs. 2 showed no significant differences regarding OS (p < 0.05). BCR::ABL1 status, ALL phenotype (T- or B-ALL), the intensity of conventional treatment applied , cytotoxic treatment for a previous malignancy or CCI (0 vs. 1 vs. 2–5) had no significant impact on OS and EFS. A comparison of OS among patients diagnosed with ALL during the first half of the study period  with those patients receiving their ALL diagnosis during the second half of the study period  showed no significant differences. For the entire patient cohort, age > 75 years (15 pts) was significantly associated with inferior OS (outcomes a. An ECOrding OS b. Refracp < 0.05)   . In a mu < 0.05) .A subgroup of 33 patients (34.4%) received an allogeneic HSCT as part of their ALL treatment . The medIn total, 23 patients (69.7%) were transplanted in 1st CR, 7 patients in 2nd CR (21.2%), and 3 patients (9.1%) were transplanted with active disease . A totalOS of the subgroup of patients receiving an allogeneic HSCT at 1 and 3 year(s) after allogeneic HSCT was 81.6% (95% CI: 68.3–94.9%) and 49.2% (95% CI: 31.7–66.8%), respectively a. RFS atThe cumulative incidence of relapse after allogeneic HSCT at 1 and 3 year(s) was 15.2% (95% CI: 6.8–33.9%) and 28.1% (95% CI: 16.2–48.9%), respectively c. The cuHere, we provide a detailed analysis of disease characteristics and outcomes for 93 elderly patients (>55 years) with B-precursor or T-ALL diagnosed between 2003 and 2020.We assume that the cohort treated in our center clearly overrepresents fit elderly patients considered suitable for intensive chemotherapy by external physicians, while unfit patients may not have been referred. Only 3.1% of all patients admitted to our center were considered unfit for intensive chemotherapy and hence primarily received the best supportive care.This assumption is supported by a recent population-based and thus unselected study cohort of ALL patients > 55 years from Sweden. A total of 80% of the patients in this cohort received intensive treatment and 20% followed a palliative approach , which iPatients with t-ALL seem to be slightly over-represented in our study as compared to the data available so far that report incidences of 2.5–9% ,27,28. TIn the group of intensively treated patients, poor performance status and older age at diagnosis were significantly associated with shorter OS in our analysis. They should be considered as risk factors for elderly ALL patients. These findings align with the Swedish study that reported age > 75 years at diagnosis as a risk factor for poorer outcomes . The MayInterestingly, BCR::ABL1 status had no impact on prognoses in our patient cohort, which is in line with previous studies showing that the introduction of TKIs eliminates the negative impact of BCR::ABL1 positivity on prognosis ,30. HistThe OS rates of 75.2% at 1 year and of 47.3% at 3 years, as well as the CR rate of 76.5% among intensively treated patients in our cohort, are in line with the results of the few previous prospective studies specifically designed for elderly ALL patients. These were completed between 2007 and 2017 and showed OS rates of 24–66% at 2 years and 23% at 5 years ) and theIn our analysis, the type of treatment regimen applied  did not significantly affect the outcome. Thus, it remains an open question whether less intensive treatments may be sufficient to treat patients > 55 years. Current recommendations of the GMALL propose the “elderly protocol” for all patients > 55 years—even if biologically judged younger. Interestingly, the Swedish population-based study, including patients diagnosed with ALL between 2005 and 2012, neither showed the clinical benefit of a newly introduced age-adapted protocol for older patients .Similar to the lack of consensus regarding the conventional therapeutic regimen, criteria for selecting patients suitable for allogeneic HSCT and the optimal conditioning therapy have not been defined . AssessmAs poor tolerance of intensive chemotherapy regimens due to toxicity is a common problem in elderly ALL patients ,4,11, loNovel agents like blinatumomab and inotuzumab ozogamicin are currently being tested in clinical trials and represent promising future therapeutic options, both as frontline and salvage therapy of B-cell precursor ALL patients . ImportaDue to small patient numbers in the respective subsets and heterogeneity of the treatment applied, no definite conclusions with regards to the impact of therapeutic options that became available during the study period—such as blinatumomab and inotuzumab ozogamicin as well as rituximab—on patients’ outcome can be drawn from our analysis. Regarding the entire patient cohort, outcomes seem to have improved only modestly between 2003 and 2020 since no significant changes in OS could be detected in those elderly ALL patients diagnosed in the first vs. the second half of the study period.Promising clinical phase II trials for patients > 55 years with B-precursor ALL such as the INITIAL-1 trial of the GMALL study group evaluating the clinical efficacy and safety of replacing conventional first-line induction chemotherapy by inotuzumab ozogamicin ,44 are cIn the subgroup of BCR::ABL1 positive elderly ALL patients (>55 years), the combination of dasatinib with blinatumomab as a “chemotherapy-free” induction and consolidation regimen has recently been evaluated in the GIMEMA LAL 2116 D-ALBA trial . The stuConsequently, the development of new treatment regimens for elderly ALL patients should focus on reducing chemotherapy intensity, especially during induction therapy, as treatment-related mortality is highest in this early treatment phase . In addiOur retrospective analysis of elderly ALL patients (>55 years) shows that intensive treatment with conventional chemotherapeutic agents is feasible in patients of this subgroup. Nonetheless, high relapse rates and impaired survival underline the need for novel therapeutic strategies. Targeted therapies such as TKIs, bispecific antibodies, and antibody-drug conjugates may represent promising treatment options, even for frail and elderly patients.


Diacronema viridis CCMP 620 was sequenced and characterized. The circular mitogenome is a total 29,282 bp in length with 39.2% GC content and contains 47 genes, including 20 protein-coding, three rRNA, and 24 tRNA genes. The gene synteny of D. viridis and D. lutheri has been highly conserved; however, the gene content (absence of introns and ORFs) and repeat regions (3.7 kbp) of D. viridis contributed to significant difference of mitogenomes within the Diacronema.The complete mitochondrial genome of the pavlovophycean microalga  Diacronema viridis  Bendif & Véron is a member of pavlovophycean microalga (Haptophytes) that is one of the important primary producer in coastal ecosystems. Recent ultrastructure, pigmentation, and molecular phylogeny supported the uniqueness and monophyly of the genus Diacronema. Six species of Diacronema shared by the unique structure of the posterior flagellum with a basal swelling and vestigial  by using a NucleoBond AXG 100 Kit . The identity of the strain was confirmed by using standard sequencing. Nuclear 18S rRNA sequence of the strain CCMP 620 was identical (100% identity) to that of Diacronema viridis KMMCC H-13 . The complete mtDNA was recovered with 876.5 average coverage . Annotation was done with program Geneious® ver. 11.1.5 (www.geneious.com) assisted by a Diacronema lutheri .Total genomic DNA was extracted from culture strain CCMP 620 denoted as unidentified D. viridis CCMP 620 (MW044629) is 29,282 bp in length, has a 39.2% GC content, encodes 47 genes  including 20 protein-coding sequences, three rRNAs and 24 tRNAs. The mtDNA (15 CDS combined data) phylogeny supported the monophyly of haptophytes (100% bootstrap support) and Diacronema   to 87.7% (atp9). The cox3 of D. viridis is only CDS comprising of two exons (764 bp and 61 bp) with an intron (839 bp) which has similar structure with that of D. lutheri, two exons with an intron (831 bp). All the other 19 CDS and three rRNAs of D. viridis have no introns, cf. the atp6, atp9, cox1 and rnl and rns rRNAs including introns in D. lutheri. Two ORFs of D. lutheri (orf105 and cox1-intronic orf636) are absent in D. viridis. Identities of the tRNAs ranged from 81.1% (tRNA-Arg) to 100% (tRNA-Gly), and those of rnl and rns rRNAs were 79.7% and 85.9%, respectively. Five repeat units  found between cox3 and rrl rRNA, i.e. two simple repeats , one tandem repeat (2 × 85 bp and 84 bp for repeat-3) and two inverted repeats . Complicated repeat regions between the genes are congruent to the mtDNAs of Diacronema such as 5.4 kbp for D. lutheri NIVA-4/92 and the longer than 2.7 kbp for D. lutheri CCMP 1325 . The new mtDNA data would contribute to the conservation and industrial application of Diacronema as marine genetic resources.New mtDNA of e; 100%) . We comp


Background: Minimally invasive mitral valve (MV) surgery has emerged as an alternative to conventional sternotomy aiming to decrease surgical trauma. The aim of the study was to describe our experience with minimally invasive MV surgery through partial upper sternotomy (PUS) regarding short- and long-term outcomes. Methods: From January 2004 through March 2014, 419 patients with a median age of 58.9 years  underwent isolated primary MV surgery using PUS. Myxomatous degenerative MV disease was the predominant pathology (77%). The patients’ mean EuroSCORE II risk profile was 3.9 ± 3.6%. Results: Mitral valve repair was performed in 384 patients (91.6%) and replacement in 35 patients (8.4%). Thirty-day mortality was 3.1%. In total, 29 (6.9%) deaths occurred during the follow-up. The overall estimated survival at 1, 5, and 10 years was 93.1 ± 1.3%, 87.1 ± 1.9%, and 81.1 ± 3.4%. Reoperation was necessary in 14 (3.3%) patients. The overall freedom from MV reoperation at 1, 5, and 10 years was 98.2 ± 0.7%, 96.1 ± 1.2%, and 86.7 ± 6.7% and the overall freedom from recurrent MV regurgitation > grade 2 in repaired valves at 1, 5, and 10 years was 98.8 ± 0.6%, 98.8 ± 0.6%, and 94.6 ± 3.3%. Conclusions: Minimally invasive MV surgery via PUS can be performed with particularly good early and late results. Thus, the PUS approach with the use of standard surgical instruments and cannulation techniques can be a valuable option for the MV surgery either in patients contraindicated or not suitable to minithoracotomy. Minimally invasive cardiac surgery continues to grow in popularity owing to improvements in surgical technique and technology, together with the acceptance of minimally invasive approaches for operations previously performed through a conventional median sternotomy ,2,3,4. AIn the late 1990s, we adopted a minimally invasive approach to valve surgery via partial upper sternotomy (PUS) which became a standard access in our institution for aortic, mitral, and multiple valve surgery, as well as for arch surgery over the years ,16,17.The aim of this study was to analyze the short- and long-term outcomes of isolated minimally invasive MV surgery through PUS with regard to survival, MV-related reoperation, and recurrent MV regurgitation.The study was approved by the local Ethical Committee of University Hospital Frankfurt, and an informed consent was obtained from each patient.Four-hundred-nineteen patients with the median age of 58.9 (interquartile range 18.7) years , who underwent minimally invasive MV surgery via PUS at the Department of Cardiovascular Surgery, University Hospital Frankfurt from January 2004 through March 2014, were included in the study. Children and adult patients with concomitant valve, coronary, or aortic surgery were excluded from the study .Before surgery, all patients were routinely examined by transthoracic echocardiography (TTE), coronary angiography, and/or cardiac computed tomography (CT). An intraoperative transoesophageal echocardiography (TEE) was performed in all patients to evaluate valve function pre- and post-cardiopulmonary bypass to facilitate the surgical procedure and to assess the immediate result of the MV surgery as well as the left ventricular function during weaning from the cardio-pulmonary bypass and adequacy of de-airing of the cardiac chambers. The echocardiographic classification of residual/recurrent MV regurgitation was as follows: grade 0—none/trace; grade 1—mild; grade 2—moderate; grade 3—moderately severe; and grade 4—severe.The postoperative anticoagulation regimen included initial subcutaneous low-molecular weight heparin for the first days and in parallel oral anticoagulation with vitamin K antagonist. Oral anticoagulation was continued for 6 weeks after an uncomplicated repair and adapted to the needs of atrial fibrillation or implanted prostheses thereafter. All patients received a TTE at discharge.All patients were followed-up prospectively and systematically by means of annually mailed questionnaires or phone interviews and/or by clinical assessment and TTE in our outpatient clinic. For patients not seen personally we retrieved the clinical assessment and echocardiography reports from the attending cardiologist.The completeness of follow-up was calculated as the portion of the actual observed patient years divided by the maximum of observable patient years as described by Akins et al. . The entThe operative technique has been previously described in detail ,16. Briep-value < 0.05 was considered to indicate statistical significance. A statistical analysis was performed using Stat view  and IBM SPSS .Valve-related outcomes were defined according to the published guidelines . ContinuMitral valve repair was performed in 384 patients (91.6%) and replacement in 35 patients (8.4%). Mainly used MV repair techniques were triangular or quadrangular resection followed by artificial chord implantation accomplished by ring annuloplasty. The majority of the patients (86%) received an open flexible ring (Cosgrove-Edwards ring). A more detailed description of repair techniques and other perioperative characteristics are provided in Thirty-day mortality occurred in 13 cases (3.1%). In eight of these patients (61%), a re-exploration due to postoperative bleeding was necessary. The cause of death was multiple organ failure in six, sepsis in three, low cardiac output syndrome in one, major stroke in one, and other causes in two patients, respectively. Other early postoperative data are shown in detail in p < 0.001), respectively.During the follow-up, 26 (6.2%) patients died. The overall estimated survival at 1, 5, and 10 years was 93.1 ± 1.3%, 87.1 ± 1.9%, and 81.1 ± 3.4% . The KapFourteen (3.3%) patients required reoperation after MV repair during the follow-up interval due to the following reasons: annulus re-dilatation and/or recurrent leaflet prolapse in 11 and endocarditis with leaflet perforation in three patients. In four patients, re-repair of the MV was successfully performed. All reoperations were performed through the full median sternotomy. The detailed data of all reoperated patients including the exact reason of reoperation are shown in p = 0.95) or regurgitation > 2 (p = 0.479) after dividing the overall cohort into repair versus replacement groups.The overall estimated freedom from recurrent MV regurgitation >grade 2 in repaired valves at 1, 5, and 10 years was 98.8 ± 0.6%, 98.8 ± 0.6%, and 94.6 ± 3.3% . The Kapp = 0.01) and decrease in MV orifice area .The TTE data at the latest follow-up of all living and non-reoperated patients are shown in Mitral valve surgery including repair or replacement, especially in complex pathologies, can be a challenging cardio-surgical procedure. Despite this fact, many surgeons worldwide perform MV surgery using a minimally invasive approach. This trend is supported by currently available evidence. Cheng and colleagues suggested minimally invasive MV surgery to be associated with decreased bleeding, blood transfusion, atrial fibrillation, sternal wound infections, ventilation time, intensive care unit stay, and length of hospital stay, and more expeditious return to the normal physical activity, whereas no differences in survival and valve re-intervention in the long-term were found .As a surgical technique, two different minimally invasive access modalities to the MV are currently available, accepted, and under widespread clinical use: 1. right lateral minithoracotomy  with usually peripheral cannulation; and 2. PUS with central cannulation and a trans-septal approach to the MV. For the surgeon who decides to use a minimally invasive approach for MV operation a decision has to be made mainly based on the type of incision and the way of cannulation. Whereas right lateral minithoracotomy MV surgery usually is performed together with retrograde femoral perfusion, the PUS technique can be applied together with standard antegrade aortic perfusion. Thus, it is a potentially valid therapeutic approach whenever retrograde femoral perfusion should be avoided , and is quite similar for patients where right lateral minithoracotomy should be avoided .In the past years, PUS has become an attractive and frequently used approach for minimally invasive aortic valve replacement . Moreovep < 0.001), which is probably due to the fact that these patients had a higher risk profile, rather than to the procedure itself. The 5-year survival of our patients receiving repair only of 89.3 ± 1.8% was even better compared to Seeburger’s series of 82.6% [The current study shows very good results of 419 minimally invasive MV procedures via PUS in an all-comers cohort with a 30-day mortality of 3.1%. Seeburger and colleagues reported outcomes in a series of 1.536 consecutive patients who underwent minimally invasive MV surgery for regurgitation through a right lateral minithoracotomy with a 30-day mortality of 2.4% . Due to of 82.6% .The freedom from MV-related reoperation and freedom from recurrent MV mitral insufficiency > grade 2 at 5 years: 96.1 ± 1.6% and 98.8 ± 0.6% and at 10 years: 86.7 ± 6.7% and 94.6 ± 3.3% respectively, were encouraging. The freedom from reoperation in Seeburger´s series was quite similar with 96.3% . In a mep = 0.01) over the follow-up period was observed. One of the reasons for the increase could be that the majority of the patients received an open flexible ring (Cosgrove-Edwards ring). Annular re-dilatation with this ring has been described and is possible, thus it could lead to recurrence of the MR. Additionally, in two of the reoperated patients an annular re-dilatation was observed and both patients were initially implanted with a Cosgrove-Edwards ring. Another finding was a slightly decreasing MV orifice area . Due to this fact, one can postulate that this is not the acute effect of annuloplasty with strong ring downsizing, but rather the effect of MV disease evolution and progression after MV repair with leaflet repair and annuloplasty sutures.The analysis comparing TTE data at discharge and at last follow-up  revealedDespite the stimulating results and some potential benefits of the PUS approach using transseptal access to the MV, there is definitely at least one major drawback. The increased rate of postoperative pacemaker implantation in nearly 5% of patients was slightly higher than in the literature of the minithoracotomy approach. However, it is comparable to other studies using the PUS access, as Oezpeker and colleagues reported a postoperative permanent pacemaker implantation rate of 4% in 103 patients . The repThis study provides short- and long-term results of minimally invasive MV surgery via PUS in a large all-comers cohort of patients. The results indicate that it can be performed safely with very good early and late results in both MV repair and replacement. In fact, the minimally invasive MV surgery via right antero-lateral minithoracotomy and peripheral cannulation is currently becoming more popular and has been adopted in the majority of centers, including our department. However, this approach demands a completely different setting, equipment, instruments, and especially thinking of the operating team. We therefore believe that the PUS approach with the use of standard surgical instruments and cannulation techniques can be a valuable alternative option for the MV surgery either in patients contraindicated or not suitable for minithoracotomy or in centers not willing or not able to establish the latter. In addition, the PUS access can even be easily extended to be used in patients requiring multiple valve surgery.


A single site, prospective, preliminary case series study included 39 patients with histologically proven liver-dominant NEN. PRRT in the form of 1.15GBq 90Y DOTATATE was given selectively into the liver via radiological catheterization of the hepatic artery, up to four times. The endpoint was radiological response (RECIST). Secondary endpoints assessed clinical well-being post-treatment, progression-free survival (PFS), overall survival (OS), and toxicity. Partial response (PR) was noted in 13% of subjects six weeks post-therapy, increasing to 24% at six months and dropping to 13% at 36 months. Disease progression (DP) was not seen at six weeks, was 5% at six months, and 47% at 36 months. Clinical response based on PS seen in 74% of patients at six weeks, 69% at six months, and 39% at 36 months had PFS and OS, respectively, of 22.7 months and 38.2 months. There was no difference in OS/PFS between those with RECIST PR and SD. One patient had significant toxicity (3%). Use of i.a. PRRT appears to be safe and effective in treating patients with liver-dominant NEN. In addition, the best OS (51 vs. 22 months) was seen when i.a. was used as an upfront treatment of bulky GEP-NEN liver metastases and not after i.v. 90Y DOTATATE. The use of i.a. 90Y DOTATATE PRRT appears to be safe and effective in treating patients with liver-dominant NEN.This study was performed to determine if intra-arterial (i.a.) administration of  Biochemical progression was defined as increase serum CgA as ULN over 10% from baseline levels. Patients were recruited if they had bulky liver metastases that had failed to respond to intravenous prior PRRT (16 patients) or had such bulky liver metastases that it was thought optimal for their first line of PRRT therapy .6/L, platelets < 100 × 106/L, creatinine level > 30 mg/L or GFR < 20 mL/min and poor performance status (PS), EOCG 3 or 4, and poorly differentiated NECG3 cancers. Contraindications also included pregnancy and known hypersensitivity to DOTATATE.Exclusion criteria for entry into the trial were as follows: Hb < 80 g/L, WBC < 2 × 1090Y DOTATATE PRRT in 16 patients (32%), and all but one patient had received long-acting somatostatin analog treatment, though this was suspended four weeks before the i.a. PRRT. Chemotherapy had previously been given to 12 (31%) patients, and local liver therapies such as selective trans-arterial embolization (TAE) and surgery had been performed on nine (23%) subjects  was administered i.v. 30 min, before the start of a 6 h i.v. infusion of 1 L of a lysine-containing amino acid solution such as Vamin 18 or Nephrotec, . The amino acid infusion used to reduce any renal accumulation of the 90Y-DOTATATE was administered as a slow bolus injection of 10 mL over 20 min via an appropriately placed catheter or micro-catheter radiologically placed into the left or right hepatic artery. In patients with bi-lobar disease, the catheter would be placed and two infusions would be administered in the right and left hepatic arteries. Selective cannulation and infusion were performed on any aberrant hepatic arteries such as the accessory segment 4 artery.The 90Y-DOTATATE with a mean activity of 1.15 GBq per session. The mean time between administrations of i.a.90Y-DOTATATE was 9.2 weeks (range 6–10 weeks); this primarily depended on the clinical condition of the patient and availability of angiography   .90Y-DOTATATE was determined using a “Bremsstrahlung” whole body scintigraphy and SPECT images using a dual-head gamma camera  equipped with medium energy collimation with a photopeak centered on 95 keV with a 50% window.Between 8 and 18 h post-therapy, the biodistribution of the An assessment of the patient’s general health and tumor-specific symptoms was performed by three observers  before treatment, then at six weeks, and then three months after their last therapy episode. At each visit, the patient’s general health was assessed using the standard ECOG performance status (PS) scale.The clinical symptoms of response on i.a. PRRT assessed in this study included appetite, malaise, weight change, the presence and intensity and frequency of abdominal pain, diarrhea, flushing, nausea, vomiting, fever, wheezing, and abdominal bloating. Analgesia and somatostatin analog requirements before and after treatment were recorded in clinical files.To assess any biochemical or endocrine toxicity, serial measurements  of plasma chromogranin-A (CgA) and if relevant 24-h urinary 5-hydroxyindole acetic acid (5-HIAA) and fasting gut hormones are performed for patients with biologically functioning pancreatic neuroendocrine tumors.Tumor response was determined by CT  and scored, according to RECIST 1.0, by two independent radiologists with a special interest in GEP-NEN tumors (AJS and JMP) who were required to reach consensus on the size change of the five largest liver metastases seen on the pre-treatment liver scans. Any new liver metastases were also noted . In addip < 0.05 was considered statistically significant.Statistical analysis was performed using Statistica v.13.1 . Differences in performance status (PS) in the ECOG scale in patients before therapy and after completed radionuclide therapy were performed using Wilcoxon’s matched pairs test. Differences between data sets of two independent samples were performed using a Mann–Wilcoxon U-test. The overall survival (OS) and progression-free survival (PFS) were estimated for the total cohort of patients using the Kaplan–Meier estimator. Overall survival (OS) was defined as the time from the first administration of i.a. therapy until death from any cause or last follow-up as censored data. PFS was calculated from the start of i.a. PRRT to recorded disease progression according to RECIST or death. Comparison of OS and PFS between different groups of patients was assessed using the Cox–Mantel test and log-rank test. The proportions of patients who had a clinical response (PS status) and CT responses were calculated separately. 90Y-DOTATATE post-therapy in almost all cases perfectly matched the pre-treatment diagnostic 99mTc-HYNICTOC imaging.Of the 39 treated GEP-NEN patients, 14 had tumors of pancreatic origin, 13 had tumors arising from the small bowel, four has tumors arising from the large bowel/rectum, and eight had metastatic NEN but with an unknown primary (CUP—cancer of unknown primary). There were 19 of these patients with secreting tumors, nine of whom had had previous i.v. PRRT. The most common histological stage was NETG2 occurring in 28 subjects (73%) compared to NETG1 in eight patients (22%) and NETG3 in two patients (5%). At the start of treatment, 29 patients (74%) had a PS of 1, eight patients (23%) had a PS of 2, and one patient had a PS of 0. Liver metastases of over 50% of total liver volume were seen in 13 patients (33%), liver metastases involving 25–50% of the liver was seen in 18 (46%), and a metastatic volume involving less than 25% of total liver volume was seen in eight subjects (21%) . All patp < 0.01 Wilcoxon matched pair test). The PS improved in 29/39 patients (74%) at six weeks after PRRT, but in two patients, the PS had deteriorated. Of the 29 patients who had an improved PS at six weeks, 27 (93%) had maintained their improved PS; by 36 months, this improvement in PS was maintained in seven patients. The PS of four patients remained unchanged throughout the follow-up periodThere was a significant clinical response as measured by the change in performance status (PS) after therapy  was 95%, and of the 37 patients imaged at 12 months post-PRRT, the DCR was 92%. There were 15 patients still alive and imaged at 36 months after PRRT with a DCR of 53%. In those patients who had received both i.v.and i.a. PRRT, the DCR was 60% compared to just 40% in those receiving i.a. PRRT only. There were five patients with a PR at six weeks, but this had increased to nine at six months without further PRRT. At six months, two patients recorded SD. No patient had a CR .p < 0.002 Mann–Whitney U test). This reflected the higher tumor bulk in patients with SD than those with a PR. Four patients in whom i.a. was given without prior i.v. treatment with initial tumor shrinkage showed an increase in tumor size by 24 months (90Y-DOTATATE (It was noted that 14 patients with PR during the follow-up had a mean tumor/liver ratio (T/L) of 0.28, compared to those patients who had only SD during follow-up with mean T/L = 0.48  and 38.2 months (CI 34.0–71.2) .90Y-DOTATATE as their initial treatment at 52.1 months (CI 44.3–104.8) compared to those who had received i.v. 90Y-DOTATATE with a median OS of 22.2 months (CI 16.3–52.3) (p = 0.02); there was a borderline difference noted in PFS 12.3 months (CI 8.7–30.5) for those who had i.a. 90Y-DOTATATE compared to 28.4 months (CI 21.4–37.6) for those who received iv. 90Y-DOTATATE first (p = 0.056) (There was a significantly different increase in median OS if patients were treated with i.a. = 0.056) .90Y DOTATATE was maintained. In those patients who had a DCR evaluated at six months, was 95%; at 12 months, it was 89%; and at 24 months in 30 alive patients, it was 73%. The median PFS (+/− 95% CI) at six, 12, and 24 months of DCR for all patients was, respectively, 23.9 months (18.0–32.9), 26.1 months (20.1–36.2), and 28.3 months (23.4–47.4)  .The most common adverse event seen was Grade 1 anemia seen at six weeks post-therapy at a rate of 39%; in addition, 32% suffered a mild Grade 1 leukopenia, also peaking at six weeks post-PRRT . There w90Y DOTATATE could be an interesting strategy in which patients with bulky GEP-NEN metastases to the liver could be treated. It would appear from our preliminary findings in this small patient group that the best overall survival is obtained by the use of at least two cycles of i.a.1.1GBq 90Y DOTATATE is given upfront for such bulky disease within the liver with no apparent increase in toxicity when compared to i.v. 90Y DOTATATE.The results of this study show that the use of i.a. 177Lu DOTATATE has become the radionuclide treatment of choice in patients with metastatic GEP-NEN [177Lu DOTATATE was 80%, and this was achieved without significant adverse events [90Y DOTATATE was 92%. However, these results are not directly comparable, as the patient groups were probably not identical, and this improved efficacy was achieved with a rate of about 4% in significant adverse events (AEs).Following the NETTER-1 trial,  GEP-NEN ,13,14,35e events . In the 90Y DOTATATE therapy was to give four cycles of 3.0-4.0 GBq, calculated to keep the renal dose below 23 Gy [90Y beta could result in more tumor destruction, but this appeared to be handicapped by the increased adverse events rate [The standard regime for systemic ow 23 Gy ,29,35. Tow 23 Gy . There ints rate ,35,36. Ints rate .90Y DOTATATE to the liver. There had been some attempts to use particulates such as 90Y resin and glass to treat liver metastases in neuroendocrine tumors, but this can lead to post-treatment embolic syndrome, and its use has tended to be limited to tumors that do not express somatostatin receptors [90Y labeled particulates or DOTATATE.Therefore, it was logical to use techniques allowing local delivery of the eceptors ,39. Comp90Y labeled somatostatin analogs via an intra-arterial catheter in the hepatic artery can improve the response rate in liver metastases. The first reports, however, either used a regime with 90Y DOTATATE but given both systemically and intra-arterially or used a different peptide such as 90Y Lanreotide [90Y Lanreotide, a 79% DCR was achieved with a median overall survival (OS) of 15 months. There was no significant toxicity in this group of patients, the majority of whom had metastases representing greater than 50% of their total liver volume [Early reports did suggest that giving the nreotide ,22. The r volume ,17,18.90Y DOTATATE in a similar group of patients from the same institutions as the patients treated in this study in which up to four cycles of 3.7 GBq each was administered showed an 87% DCR at six months post last therapy very similar to the 92% achieved in patients with liver metastases treated with at least two sessions of i.a. injection of 1.15 GBq each of 90Y DOTATATE in the current study. The mean cumulative activity administered in this study was only 3.13 GBq for all patients and was lower in those with previous i.v. PRRT vs. only i.a. 2.8 vs. 3.4 GBq, respectively. In our previous study, the mean administered activity in i.v. therapy was 11.2 GBq, which is almost four times greater than in subjects in the current trial who had initially (only) i.a. PRRT [Previously reported use of systemic 90Y DOTATATE, the median PFS was 17 months (CI 16.4-21.2) compared to 24.1 months (CI 16.7-30.9) with the current i.a. 90Y PRRT. The median OS for those treated with systemic 90Y DOTATATE was 22 months (CI 20.4-26.7) compared to 38.2 months (CI 34.0-71.2) for those receiving i.a. 90Y DOTATATE [With the systemic administration of Another potential explanation of our results in both groups of patients who had current i.a. therapy was the selection of more aggressive tumor cell lines surviving treatment by previous i.v. PRRT in those patients who then relapsed and were treated with further i.a. PRRT. This phenomenon probably related to the natural history of the development of GEP-NEN, with the survival of more aggressive clones of cancer cells after anticancer therapy, like PRRT, meaning those clones of cells that survive are less sensitive to second-time beta irradiation .177Lu DOTATATE, where both partial response (PR) and disease stability (SD) as assessed by radiological criteria were related to a good overall prognosis [90Y DOTATATE in our previous reports [90Y DOTATATE could be used safely after previous systemic PRRT, but that sequential treatment may not be the ideal scenario in this difficult group of subjects, and upfront i.a. 90Yttrium DOTATATE may be the best way forward in those patients with bulky liver metastases from GEP-NEN tumors.The lack of radiological PR has been noted before in GEP-NEN patients treated with radioisotopic therapy in many others reports ,15,17,18rognosis . In the  reports . The imp90Y DOTATATE, as the reported Grade 3 and four toxicity (AEs) rate for those receiving systemic 90Y DOTATATE was 10% compared to just 3% in those treated with i.a. 90Y DOTATATE. As the patients treated by these two studies may have a number of different characteristics, the primary one being the liver-dominant disease in the i.a. group, it can be noted that it is unlikely that the i.a. 90Y DOTATATE is less effective and more toxic than the use of systemic 90Y DOTATATE. It is useful to note the Grade 3 and 4 hematological toxicity was 9% in those treated with 177Lu DOTATATE on the NETTER1, which is higher than seen in our group of patients treated with i.a. 90Y DOTATATE [90Y DOTATATE is as effective and certainly no more toxic than the standard four cycles of 7.4GBq 177Lu DOTATATE. However, the small number of patients within our study group means that further work in this area in a bigger patient group would be needed to confirm these findings.In this trial, we noted a low rate of any AEs compared to the group of patients who were treated previously using i.v.DOTATATE ,19. Thou90Y DOTATATE six weeks apart may be as effective and safe as the recommended cumulative activity of 28 GBq of 177Lu DOTATATE or 14 GBq of 90Y DOTATATE given over i.v. at eight months in those patients with bulky liver GEP-NEN metastases, with some evidence of improvement in overall response rate, including disease control rate (DCR), clinical response (PS), and also PFS and OS when given as upfront i.a.90Y DOTATATE. A larger multi-center trial should now be considered to determine if such an approach should be considered as an alternative or adjunctive form of PRRT in those with liver-dominant unresectable GEP-NEN metastases in their liver.The conclusion of this preliminary study is that treatment with two cycles of 1.1 GBq i.a.


Dexamethasone increased mortality compared with usual care in patients not requiring oxygen supplementation, leading to a NNH value of 26.7 . NNT of dexamethasone vs. usual care was 17.3 (95%CI 14.9–20.6) in subjects <70 years, 27.0 (95%CI 18.5–49.8) in men, and 16.2 (95%CI 13.2–20.8) in patients in which the onset of symptoms was >7 days. Dexamethasone is effective in male subjects < 70 years that require invasive mechanical ventilation experiencing symptoms from >7 days and those patients receiving oxygen without invasive mechanical ventilation; it should be avoided in patients not requiring respiratory support.A clinical interpretation of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study was performed to provide a useful tool to understand whether, when, and to whom dexamethasone should be administered during hospitalization for COVID-19. A post hoc analysis of data published in the preliminary report of the RECOVERY study was performed to calculate the person-based number needed to treat (NNT) and number needed to harm (NNH) of 6 mg dexamethasone once daily for up to 10 days vs. usual care with respect to mortality. At day 28, the NNT of dexamethasone vs. usual care was 36.0 (95%CI 24.9–65.1,  The updated guidance of the American Thoracic Society (ATS) and European Respiratory Society (ERS) International Task Force for the management of coronavirus disease 2019 (COVID-19) has recently suggested to use dexamethasone in hospitalized patients who require supplemental oxygen or are mechanically ventilated , where Sa and Sc are the survival probabilities in the dexamethasone and usual care groups, respectively, na and nc are the number of patients still at risk  in the dexamethasone and usual care groups, respectively.NNT and NNH were calculated as follows: NNT = 1/ARR and NNH = 1/AAI, respectively; the 95%CI of NNT and NNH were calculated as follows: 95%CI of NNT = ARR ± 1.96 * SE(ARR) and NNH = ARR ± 1.96 * SE(ARI), where SE is the standard error ,9. ARR oSubset analyses were carried out on age, sex, and onset of symptoms to identify potentially confounding factors with respect to the NNT and NNH of dexamethasone vs. usual care.p < 0.05.ImageJ was used to extract data from the figures, when necessary  and GrapDetails regarding the raw data extracted at specific time-points from the RECOVERY study  accordinp < 0.05) and ranged between 28.0 and 37.4 (p < 0.05) and time-dependent trend for which the NNT values of dexamethasone vs. usual care started from 17.4 at 7 days since randomization and improved up to 8.5 after four weeks of treatment (p <0.05) superior to usual care, with NNT values ranging between 22.5 and 32.0 , our analysis shows an evident and statistically significant (p < 0.05) harm of dexamethasone vs. usual care after 14 days since randomization, with the worst NNH value of 26.7 at the end of the study (While the RECOVERY study  reportedhe study D. Detailp < 0.05) NNT values of dexamethasone vs. usual care in subjects younger than 70 years (17.3 95%CI 14.9–20.6), in men (27.0 95%CI 18.5–49.8), and in those patients in which the onset of symptoms was >7 days (16.2 95%CI 13.2–20.8). In subjects ≥70 years of age, women, and those patients in which the onset of symptoms was ≤7 days, no significant (p > 0.05) NNT values were detected .When considering potentially confounding factors according with the primary publication , we founThe results of this analysis provide the evidence that only ≈8 patients receiving invasive mechanical ventilation had to be treated with dexamethasone to prevent one death compared to usual care over 4 weeks, whereas in patients receiving oxygen only (with or without noninvasive ventilation), one death was prevented for every 35 patients. Thus, it seems that the benefits of dexamethasone are related with the severity of illness, at least in those patients receiving respiratory support. In fact, in less severe patients not requiring oxygen supplementation, dexamethasone not only provided no benefit but it even induced a significant harm, leading to one death every ≈27 patients when compared with usual care.Interestingly, our analysis supports the possibility that dexamethasone may induce harm in patients who did not require oxygen as resulting from the RECOVERY study . In thisTherefore, also in the light of the NNT values resulting from potentially confounding factors, the hospitalized COVID-19 patients that may receive the greatest benefit from the treatment with 6 mg dexamethasone once daily for up to 10 days are those male subjects younger than 70 years that require invasive mechanical ventilation and experiencing symptoms from more than 7 days, followed by those receiving oxygen without invasive mechanical ventilation. While in women and subjects elderly than 70 years dexamethasone seems to induce neither benefit nor harm, the findings provided by our analysis indicate that its use should be avoided in those patients not requiring respiratory support.The reasons why dexamethasone is more effective in patients receiving respiratory support and in those enrolled after the first week of disease have already been discussed in the preliminary report of RECOVERY study , whereasAlthough it has been suggested that the treatment beneficial effect on mortality is a general effect of class of corticosteroids and not specific to any particular agent , solid e


Entamoeba histolytica was the most predominant parasite  while Giardia lamblia was the least . Consumption of vended or borehole water and hygienic practices such as hand washing before eating, after using toilet, before cooking and trimming of finger nail and wearing proper working clothes and shoes were statistically significant with intestinal parasitic infection (P < 0.05). Generally, the prevalence of intestinal parasitic infection in this study was high and contributed by low socioeconomic status and poor environmental and personal hygiene. Measures including education on personal hygiene, environmental sanitation, drinking water supply, regular medical checkups, and treatment should be taken into account to reduce the prevalence of intestinal parasites.Intestinal parasites are responsible for one of the major health problems like food contamination with socioeconomic effects in the world with a prevalence rate of 30-60%, in developing countries that lie within tropical and subtropical areas. They pose a reasonable public health burden, particularly in low- and middle-income countries, including Ethiopia. Globally, due to intestinal parasitic infections, around 3.5 billion people are affected and more than 200,000 deaths are reported annually. Around 50000 deaths yearly are caused by intestinal parasites in Ethiopia. As such, intestinal parasites perceived global and local burdens to various countries. The risk of food contamination depends largely on the health status of the food handlers, their hygiene, knowledge, and practice of food hygiene. Food handlers with poor personal hygiene and sanitation conditions are the major potential sources of intestinal helminthes and protozoa worldwide. The proposed study was aimed at evaluating prevalence of intestinal parasitic infections and their associated factors among food handlers working in selected catering establishments. A cross-sectional study was conducted in Bule Hora Town from March to April 2020. A total of 136 catering establishments were selected using a systematic sampling technique. Data analysis was done using SPSS version 20. The prevalence of intestinal parasites in this study was 46.3%.  Infections caused by intestinal parasites are widespread causing significant problems in individuals and public health, particularly in developing countries, with a prevalence rate of 30-60.0% . In addiGlobally, due to intestinal parasitic infections, some 3.5 billion people are affected; 450 million are symptomatic, and yearly more than 200,000 deaths are reported [Reports indicate that food handlers working in hotels, hostel mess, and other catering services reported personal hygiene and sanitation conditions which are the major potential sources of intestinal helminthes and protozoa from many developed and developing countries all over the world –8. IntesTaenia saginata, Hymenolepis nana, Ascaris lumbricoides, Strongyloides stercoralis, Trichuris trichiura, and Enterobius vermicularis and hookworms predominantly Necator americanus and Ancylostoma duodenale as well as the protozoans mainly Giardia lamblia and Entamoeba histolytica are the major intestinal parasites leading to digestive disorders [Ascaris lumbricoides (roundworm). Entamoeba histolytica, which causes amoebiasis, is estimated to cause severe disease in 48 million people, killing 54,000 each year. Multiple infections with several parasites  are common, and their harmful effects are often aggravated by coexistent malnutrition or micronutrient deficiencies [The helminthes isorders . Accordiisorders  every yeciencies .In Africa, particularly sub-Saharan Africa, a study carried out over a ten-year period between 1999 and 2009 reported a 30.2%-55.6% prevalence of intestinal parasites among the vast majority of the people . With thThe spread of disease by food handlers is a common and persistent problem globally . Food haUnfortunately, data is lacking on the burden of intestinal parasites among those eating and drinking establishments from Bule Hora Town, Ethiopia. Therefore, the proposed work was a first attempt to determine the prevalence and risk factors associated with the food handlers among selected places from the studied area.Bule Hora Town is a town situated in the southern part of Ethiopia. It is located on the paved Addis Ababa-Moyale highway in the West Guji Zone of the Oromia region. It has a latitude and longitude of 5°35′N and 38°15′E, respectively, and an altitude of 1716 meters above sea level . The 201A descriptive cross-sectional study was conducted between March and April 2020, and both quantitative and qualitative approaches were preferred to gather desirable information. The data was gathered from a pool of participants with varied characteristics and demographics known as variables. It contains multiple variables at the time of the data snapshot.The study population includes all catering establishments like hotels, bar and restaurants, cafe and restaurants, dining rooms, cafes, food and groceries, cafeteria found in Bule Hora Town, and all persons employed and working as food handlers in the above selected catering establishments.The formula by Yamane  was usedN is the population size and e is the level of precision. Therefore, from a preliminary study, we have 408 catering establishments in Bule Hora Town. Hence, the size of our sample was calculated as follows:where 2) is equal to 3; therefore,Assuming 1 + 408 th, i.e., “408/3 = 136,” catering establishment was included in the sample where n ranges from 1 to 136. For food handlers from establishments, those who have greater than one food handler, at least one person who has a close contact with food (preparing foods) and food contact surfaces and equipment which was selected by a random sampling method and those who have only one food handler, he/she was directly involved in the research and keenly observed for the assessment of personal hygiene and hygienic practice and also interviewed to assess kitchen activity performance. Additionally, health status assessment and stool examination were also done [All catering establishments employed workers (whether on a temporary or permanent basis) who handle the food, which were constituted in the sampling frame. For catering establishments, the census was done first to get a list of each different type of catering establishments from a selected place, which was found to be 408 in total. Finally, 136 of the catering establishments were selected by a systematic sampling technique. Hence, every  of the respondent was labeled on the submission of the stool sample. A portion of the stool was preserved in 10% formalin for helminthes, and for protozoans, it was preserved in 5% formalin. The stool specimens were transported in an ice box immediately to the Bule Hora general hospital for laboratory analysis .Direct stool examination was carried out according to the techniques described previously . BrieflyThe concentration technique was carried out using 3 g of fresh stool sample emulsified in 7 mL of formal saline as mentioned previously [The chi-square test was used to test for the significance level. The association between intestinal parasitic infection and sociodemographics, knowledge, and practices was calculated using the Poisson regression at 95% of confidence level. All statistical analyses were performed using SPSS version 20 .A total of 136 participants working in 136 different catering establishments who met the inclusion criteria were recruited into this cross-sectional study.χ2 = 14.000; df = 5; P = 0.001) (From dining rooms (49 (36.0%)), hotels (39 (25.8%)), bars and restaurants (19 (14.0%)), cafe and restaurants (12 (8.8%)), groceries and dining rooms (11 (8.1%)), cafe (7 (5.1%)), and cafeteria (3 (2.2%)) participants were sampled . A signi= 0.001) .χ2 = 8.389; df = 1; P = 0.001)  males versus 90 (66.2%) females was studied. Consequently, there were significantly more females relative to male participants (= 0.001) .χ2 = 19.000; df = 3; P = 0.001) (The mean age of the participant was 24.73 (±3.226) years with a median of 25 years (range 20 to 37 years). The majority of the object ) participants were aged between 21 and 30 years while the least 8 (5.9%) were aged from 31 to 37. A significant difference was noted in the distribution of study participants with regard to age (= 0.001) .χ2 = 14.268; df = 3; P = 0.001).95 (69.9%) of the participants had a secondary level of education. The remaining 33 (24.3%) were having a tertiary level of education while the least ) attended primary or basic education . A signiχ2 = 4.067; df = 3; P = 0.001) (93 (69.8%) of the study participants were found to be single. 39 (28.7%) of them were married while 4 (2.9%) of them were currently divorced. There was a significant difference observed in the distribution of study participants with regard to marital status (= 0.001) .χ2 = 14.268; df = 2; P = 0.001) (The mean number of the participant's household population was 2.51 (±0.827) persons with a median of 2 (range 0 to 3 persons). The majority (41 (30.1%)) of the participants were from a household with 1 to 3 occupants while 2 (1.5%) have no children. A significant difference was found in the distribution of study participants with regard to the household population (= 0.001) .χ2 = 29.617; df = 4; P = 0.001) (About 3 (2.2%) of the participants earned 10-25 USD, 59 (43.4%) has an income of 25 to 40 USD, 43 (31.6%) generate 40 to 50 USD, 9 (6.6%) have 50 to 65 USD of monthly income, and 22 (16.2%) have 65 USD and above as their monthly income. A significant difference was associated with the monthly income of study participants (= 0.001) .χ2 = 58.148; df = 2; P = 0.001) ) of the participants resided in a rental house while 55 (40.4%) live with the owners of the establishments, 21 (15.4%) are living with family, and 2 (1.5%) have their own house. A significant difference was observed in the distribution of study participants with regard to housing type (= 0.001) .χ2 = 9.356; df = 3; P = 0.001) ) of the study participants used firewood as a cooking source while 12 (8.8%) preferred electric energy for cooking purpose. A significant difference was found in the distribution of study participants in terms of their energy for cooking (= 0.001) .χ2 = 76.101; df = 2; P = 0.001) (119 (87.5%) of the participants used electricity as their light energy source. Other ) used kerosene while 9 (6.6%) used solar energy as a source of lighting. A significant difference was recorded in the distribution of study participants with regard to the household lighting energy source (= 0.001) .χ2 = 13.101; df = 3; P = 0.001).A maximum number of participants ) were aware of intestinal parasites compared to 57 (41.9%) who had no knowledge about intestinal parasites . A signiχ2 = 8.322; df = 1; P = 0.001). 13 (9.6%) of the participants were aware of the frequency of these medical examinations yearly in comparison to 123 (90.4%) participants who were not aware. Of those who were aware of the frequency of medical examination, 5 (38.5%) responded that they usually performed medical checkup twice per year and 8 (61.5%) responded that they used to carry out medical checkup routinely three times annually (About 123 (90.4%) of the study participants were not aware about the purpose of medical examination when compared to the 13 (9.6%) remaining population. A significant difference was recorded for the distribution of study participants with regard to knowledge for medical examination  (Nearly 123 (90.4%) of the participants were not aware of the legal consequences for not taking the regular medical examinations to their counterpart who were aware and said they have no information towards the consequence 13 (9.6%). A significant difference was seen towards the distribution of study participants with regard to knowledge on the legal consequences for the lack of medical examination (= 0.003) .A significant difference was noted towards the study participants based on the knowledge of the types of intestinal parasites. From the survey, the researcher asked 79 (58.1%) participants who said they are aware of intestinal parasites along with signs and symptoms associated with intestinal parasite infection. The majority (40 (50.6%)) of respondents stated diarrhea followed by 17 (21.5%) who were aware of stomach ache. Others included 15 (19.0%) who said fever, and 7 (8.9%) stated the presence of blood in stool .χ2 = 62.067; df = 1; P = 0.001).As highlighted in χ2 = 7.732; df = 1; P = 0.005) ) of study participants worked in catering establishments that had specific people employed to clean work places and toilets compared to 70 (51.5%) who did not have such kind of employees and facilities. There was a significant difference observed in the frequency of study participants based on the presence of specific people employed to clean work place and toilets (= 0.005) .χ2 = 62.914; df = 1; P = 0.05). The majority ) of the participants acknowledged wearing of protective clothes during cooking in comparison to 49 (36.1%) who did not use such protection in kitchen. A significant difference was recorded in the frequency of study participants based on the practice of wearing protective clothes   respondents stated that they cut their nails regularly than those of 13 (9.5%) who were habituated of trimming the nails rarely. No significant difference was seen in the frequency of study participants based on how regularly they cut their nails (= 0.001) .χ2 = 30.550; df = 4; P = 0.001).61 (44.8%) of study participants said that they used to do for eating purpose. 31 (22.8%) stated two purposes of hand washing, i.e., for eating and cooking. 19 (14.0%) used to wash their hands after using the toilet, 18 (13.9%) of them mentioned that they clean their hands for cooking purpose, and 7 (5.1%) said that they used to wash their hands for cooking, eating, and after using of toilet . A signiP = 0.001).129 (94.9%) participants had formed stool, 5 (3.7%) had semiformed stool, and 2 (1.4%) had loose stool . A signiEntamoeba histolytica. Others included 14 (22.2%) carrying Ascaris lumbricoides, 12 (19.0%) participants had Taenia saginata, 9 (14.3%) respondents had hookworm, and 7 (11.1%) were associated with Giardia lamblia .63 (46.3%) were carriers of intestinal parasites while 73 53.7%) had no cysts, trophozoites, larva, or eggs detected in their stool sample. Among 63 participants that were found to be positive for intestinal parasites, the majority (21 (33.3%)) were carrier of 3.7% had Bivariate and multivariate analyses of demographic factors revealed that none of participant's demographic variables such as work place, age, education level, marital status, and household population size were found to be associated with intestinal parasite infections .Participants whose household consumed vended or borehole water were more likely to be infected with intestinal parasite compared to those who had town municipal tap water facility. Generally, poor socioeconomic status had contributed to high prevalence of intestinal parasitic infection .As shown in Food handlers have potential of carrying a wide range of enteropathogens and have been implicated in the transmission of many infections to the public in the community and to patients in hospitals. Reports globally have emphasized the significance of food handlers with poor personal hygiene as a risk of transmission of parasitic and bacterial diseases . There aThis study is among the first report on the prevalence and correlates of intestinal parasitic infection among food handlers within the Bule Hora Town clientele. The overall prevalence of intestinal parasite infections was 46.3%. The high prevalence of intestinal parasitic infections (46.3%) in this study among food handlers was in agreement with the findings of other studies conducted in Ethiopia like Addis Ababa 45.3%) , Yebu To.3% , YebE. histolytica followed by 14 (22.2%) with Ascaris lumbricoides, 12 (19.0%) with Taenia saginata, 9 (14.3%) with hookworm, and 7 (11.1%) with Giardia lamblia , Ascaris lumbricoides (26.4%), and G. lamblia (1.6%) was reported in Ethiopia from Nekemte Town [E. histolytica (56.6%), Ascaris lumbricoides (26.4%), and G. lamblia (1.6%)—Addis Ababa [G. lamblia as the leading parasite followed by other parasites such as those in Bahir Dar, Ethiopia [Giardia parasite as one of 6 common types of parasites among members of restaurant staff.In this study, the majority of parasitic infection (21 33.3%)) was  Figures  and 6. Smte Town  . Other Ethiopia , and in Ethiopia . Kamau e3.3%) wasThis study did not find any relationship between intestinal parasitic infection and participant's residency, age, education level, marital status, income, and household population size . HoweverConcerning the relation of the age group and parasitic infection, cumulatively although not significant, the study revealed relatively a higher infection rate in the age group younger than 30 years. No significant difference was found in the distribution of parasitic infection among all age groups which showed that there is equal exposure to the infection and suggests an effect of environmental conditions on the infection. This outcome is similar to various reports in India, Ethiopia, and other regions of the world –50. AnotResults of our study also revealed a significant overall relationship between food handler‘s sanitation and hygiene and intestinal parasitic infection. Food handlers hand washing reasons for the purposes of eating, after using the toilet, cooking or two of these reasons were less likely to get intestinal infections. On the other hand, food handlers who wore general protective headgears were more likely to get intestinal parasitic infections. Other studies have also reported several environmental and behavioral variables significantly contributing to intestinal parasite infection . Like inNotably, this study did not report any association towards the respondent's knowledge-related factors  to intestinal infection. Based on the participant's responses, it can be concluded that generally intestinal parasitic literacy level was higher in this population. A study in Southeast Asia showed that food handlers had relatively less knowledge about these infections; thus, there are more infections in those regions , while tE. histolytica while hookworm and G. lamblia were the least common. Low socioeconomic status indicators such as utilization of vended or bore hole water and general poor personal hygiene were the major risk factors for the high prevalence of intestinal parasitic infection among food handlers found in our report. Therefore, mitigating steps such as enforcement of systems that promote improvement of personal- and facility-level hygiene, more public training, and wider enforcement of medical certification policy are vital to possibly reduce the risk of parasite infections.The prevalence of intestinal parasitic infection was high (46.3%) among food handlers showing high prevalence and thus consistent to other previous studies in Ethiopia and elsewhere. Most of the food handlers just as in other regions were infected with


Dear Editors,p = 0.009), had lower eGFR (p = 0.021) and were more often treated with prednisolone (p = 0.042) as shown in Solid organ transplant patients are at high risk for severe or fatal COVID-19 . Recent p < 0.001). In the patients treated with belatacept, only one out of 12 (8.3%) vaccinated individuals had a seroconversion, whereas both naturally infected patients showed a response. In a multivariable logistic regression analysis infection compared to vaccination  and transplantation vintage  were associated with a significantly higher likelihood of seroconversion. On the other hand, older age  and belatacept treatment  significantly decreased the likelihood of seroconversion. All model coefficients and odds can be found in the The seroconversion rate in convalescent patients was 90.9 and 48.6% in vaccinated patients (Like our results in convalescent KTR, Magicova et al. recently found a preserved humoral response after SARS-CoV-2 infection comparable to immunocompetent persons in a large Czech cohort of 1,037 kidney transplant recipients with a seroprevalence of 6.8% during the second infection wave in fall 2020 . In line


We investigated the agreement and accuracy of preoperative magnetic resonance imaging (MRI) with postoperative pathological characteristics and stages of endometrial endometrioid carcinoma (EEC).We recruited 527 women with EEC who underwent staging surgery at a single medical institution. The preoperative MRI, stages, and clinical and pathological parameters, including myometrial invasion (MI), cervical invasion (CI), adnexal metastasis (AM), intra‐abdominal metastasis, and pelvic and/or para‐aortic nodal metastasis, were recorded and analyzed. The agreement and accuracy between the preoperative MRI findings and these parameters and stages were assessed.The rate of the preoperative MRI‐based clinical stage matching the postoperative surgical stage was 85.2% in International Federation of Gynecology and Obstetrics stage IA, 51.9% in stage IB, 35.5% in stage II, 5.3% in stage IIIA, 33.3% in stage IIIB, 28.6% in stage IIIC1, 64.3% in stage IIIC2, and 93.8% in stage IVB. The consistency between radiologists and pathologists was 80.5% for deep MI, 91.5% for cervical invasion, 92.2% for adnexal metastasis, 98.9% for intra‐abdominal metastasis, and 87.5% and 92.2% for pelvic and para‐aortic nodal metastases, respectively. The negative predictive value of intra‐abdominal metastasis was the highest with 99.8%.Preoperative MRI could be an excellent tool for routine preoperative assessment to predict pathological parameters and stages of EEC, especially in excluding intra‐abdominal metastatic disease. Preoperative magnetic resonance imaging (MRI) had good correlations with the pathologic parameters and stages of endometrial endometrioid adenocarcinoma. Preoperative MRI had high NPVs for disease extent, particularly the extra‐uterine spread. Preoperative MRI could provide an excellent tool for routine preoperative assessment of endometrial carcinoma patients. Approximately 86% of uterine cancers are carcinomas.Because staging depends on postoperative findings, the estimated stage and risk of extrauterine disease determines the extent of surgery. Extrauterine spread, the depth of myometrial invasion (MI), tumor grade and histological subtype, and lymph node metastases are the factors considered in endometrial cancer prognosis.The guidelines recommend MRI for estimating the preoperative stage because of the better resolution of soft tissue contrast for assessing the depth of myometrial or cervical invasion compared to CT.Several studies have reported the assessment of preoperative image reliability, but numbers of patients are limited and not all risk factors were discussed.22.1A total of 1020 patients with EC were identified from the National Taiwan University Hospital covering the period from January 1, 2013, to December 31, 2018. This study was approved by the Institutional Research Ethics Committee at the National Taiwan University Hospital. All of the patients’ data were fully anonymized before we accessed them and the Research Ethics Committee waived the requirement for informed consent. All patients were diagnosed by endometrial biopsy or curettage, with confirmation by hysterectomy. We excluded cases in which patients did not undergo hysterectomy because of personal reasons, were not available for preoperative MRI at our hospital, were not good candidates for surgery, had undergone surgery at another hospital, had incidental cancer such as ovarian cancer after the hysterectomy, or had undergone surveillance at the other hospitals after surgery. We also excluded 66 patients with other histological types, including serous and clear cell carcinoma, adenosarcoma, carcinosarcoma, leiomyosarcoma, and neuroendocrine carcinoma. Data of the remaining 527 patients were eligible for further analysis Figure .2.2b‐values, 0, and 800 s/mm2) for the whole pelvis. Examinations performed after 2018 also included a sagittal DW‐EPI of the uterus. Apparent diffusion coefficient (ADC) maps were derived from the diffusion‐weighted sequences, generated by the scanner software. The patients received intravenous gadolinium contrast medium  if there were no contraindications. Post‐contrast images include T1‐weighted three‐dimensional‐spoiled GRE sequence with FS in the sagittal, coronal, and axial views. Images of the upper abdomen were also obtained to detect possible metastases. The pulse sequences for upper abdomen include an axial T1‐weighted GRE sequence with FS, an axial T2‐weighted FSE sequence with FS, and post‐contrast T1‐weighted three‐dimensional‐spoiled GRE sequence with FS in the coronal and axial views. The details of these pulse sequences are summarized in Table All of the 527 patients underwent abdomino‐pelvic MRI to examine upper abdomen. The chest CT scan was only performed when suspected pulmonary metastasis by CxR or clinical symptoms such as cough. MRI examinations were performed using a 1.5‐T MRI unit . The pulse sequences for pelvic imaging included T2‐weighted fast spin echo (FSE) sequences in the sagittal, coronal oblique, and axial oblique views according to the axis of the uterine body, an axial T2‐weighted FSE sequence with fat saturation (FS) of the whole pelvis, an axial T1‐weighted gradient‐echo (GRE) sequence with FS, and an axial diffusion‐weighted echo‐planar imaging (DW‐EPI) sequence , negative likelihood ratio(LR−), and kappa of MRI for determining the clinicopathological parameters. LR+ is the probability that a parameter of interest that is present was detected on MRI (true positive) divided by the probability that a parameter that is not present was detected on MRI . The higher the LR+, the more useful the positive finding will be considered. Conversely, LR− is equivalent to the probability that a person with the parameter had a negative result for it on MRI  divided by the probability that a person without this parameter tested negative for it (true negative).33.1n = 338, 64.1%) were post‐menopausal. Overall, 409 (77.6%) patients presented with FIGO stage I, 31 (5.9%) with stage II, 71 (13.5%) with stage III, and 16 (3.0%) with stage IVB disease. A total of 517 (98.1%) and 10 (1.9%) patients had endometrioid histology and endometrioid with other histologic types, respectively. Histological grade 1 was most common , followed by grade 2  and grade 3 . Of the whole cohort, 55 patients (10.4%) had malignant cells and 38 (7.2%) had cells with atypia of undetermined significance in their washing cytology or ascites. Pelvic lymph node sampling or dissection was performed in 98.3% of patients and para‐aortic lymph node sampling or dissection was in 24.3% of patients (Table The characteristics of the 527 patients are provided in Table 3.2n = 153) had ≥50% MI, 11.8% (n = 62) had CI, 7.4% (n = 39) had AM, and 2.3% (n = 12) had intra‐abdominal metastasis. Pelvic lymph node metastases were identified in 54 patients (10.2%) and para‐aortic lymph node metastases in 16 patients (2.9%). Figure Regarding the preoperative MRI findings, we analyzed six parameters of interest, including MI, CI, AM, intra‐abdominal metastasis, and pelvic and/or para‐aortic nodal metastasis Table . Of the 3.3We also evaluated the agreement between MRI‐based clinical stages and surgical stages Table . The top3.4Table 3.5The sensitivity, specificity, PPV, and NPV of predicting CI were 53.2%, 96.6%, 67.4%, and 93.9%, respectively. The LR+ was 15.6 (53.2%/3.4%), suggesting that when preoperative MRI showed CI, the patients would be 15.6‐times more likely to have CI than the patients in whom imaging did not show CI. The LR− was 0.48 (46.8%/96.6%), indicating that a negative result had an approximately 50% chance of being adjudicated in a person with CI as in a person without it. The agreement for CI between radiologists and pathologists was 91.5%, and the degree of underestimating and overestimating CI on preoperative MRI was 5.5% and 3.0%, respectively.The sensitivity, specificity, PPV, and NPV of predicting AM were 25.6%, 97.5%, 45.5%, and 94.3%, respectively. The LR+ was 10.2 (25.6%/2.5%), indicating that when the preoperative MRI revealed AM, a patient would be 10.2‐times more likely to have AM than when imaging did not show it. The LR‐ was 0.76 (74.4%/97.5%); therefore, a negative result carried an 80% chance that someone with AM on MRI would have AM compared to a person without it. Radiologists and pathologists had 92.2% agreement on this parameter. The degree of underestimating and overestimating AM on preoperative MRI were 5.5% and 2.3%, respectively.The sensitivity, specificity, PPV, and NPV of predicting intra‐abdominal metastases were 91.7%, 99.0%, 68.8%, and 99.8%, respectively. The LR+ was 93.6 (91.7%/0.98%), indicating that when the preoperative MRI revealed intra‐abdominal metastasis, a patient would be 93.6‐times more likely to have intra‐abdominal metastasis than when imaging did not show it. The LR− was 0.084 (8.33%/99.02%). Radiologists and pathologists had an accuracy of 98.9% when identifying intra‐abdominal metastases. The degree of underestimating and overestimating intra‐abdominal metastases on preoperative MRI were 0.2% and 1%, respectively. There were four clinical stage IVB patients with the metastatic lesions in supraclavicular node, bone, and labia which were excluded in the statistical analysis due to the outfield of abdomino‐pelvic MRI examination. Omental metastasis was the most common intra‐abdominal lesion in all stage IVB patients  following by the intestine metastases . There were two patients with omental and intestinal metestases.The sensitivity, specificity, PPV, and NPV of predicting pelvic nodal metastasis in patients who underwent pelvic lymph node dissection were 46.3%, 92.2%, 41.0%, and 93.7%, respectively. The LR+ was 5.9 (46.3%/7.8%), and the LR− was 0.58 (53.7%/92.2%). The agreement between radiologists and pathologists in identifying pelvic nodal metastasis was 87.5%. The degree of underestimating and overestimating pelvic nodal metastasis on preoperative MRI were 5.6% and 7.0%, respectively.The sensitivity, specificity, PPV, and NPV for para‐aortic nodal metastasis in 128 patients who underwent para‐aortic lymph node dissection were 68.8%, 95.5%, 68.8%, and 95.5%, respectively. When the preoperative MRI revealed para‐aortic nodal metastasis, the patients were15.3‐times likely to have para‐aortic nodal metastasis compared with those without . The LR− was 0.33 (31.2%/95.5%). The accuracy of determining para‐aortic nodal metastasis was 92.2%, with good agreement between radiologists and pathologists, and the degree of underestimating and overestimating this parameter on preoperative MRI was 3.9% and 3.9%, respectively.3.6p = 0.0014, Z‐test). The accuracies of the other parameters were no different. Whereas, the accuracies of various parameters between 2013 and 2018 were no different  could contribute to the low decrease the accuracy rate of preoperative MRI. Furthermore, many of the stage II to stage IIIC1 diseases such as cervical stromal or vaginal invasion, and adnexal or pelvic lymph node metastasis were microscopic lesions which could be missed by MRI.A strength of our study is that a large number of patients were recruited. All images were interpreted by qualified and well‐experienced radiologists for the routine MRI examination of endometrial cancer. We applied several statistical methods to calculate inter‐rater reliability which was not performed in one previous study. The retrospective design of our study represents the major limitation and may introduce selection bias. We only recruited patients who underwent preoperative MRI at our hospital. It could be a limitation related to bias toward greater consistency in radiology reports. Another limitation was that not all patients underwent pelvic and para‐aortic lymph node dissection, which decreased the statistical power.In conclusion, our results indicated that preoperative MRI had good correlations with the pathologic parameters and stages of endometrial endometrioid carcinoma. Preoperative MRI had high NPVs for disease extent, particularly the extrauterine spread. Preoperative MRI could provide an excellent tool for routine preoperative assessment of EC patients and is helpful to optimize the surgical approach. Surgeons should be aware of the pitfalls in each parameter in preoperative MRI image to decrease the discrepancies in clinical and pathologic stages.This study was approved by the Institutional Research Ethics Committee at the National Taiwan University Hospital . All of the patients’ data were fully anonymized before we accessed them and the Research Ethics Committee waived the requirement for informed consent.No potential conflict of interest was disclosed.CY Wu and WF Cheng: Conception and design. CY Wu, IL Shih, and WF Cheng: Development of methodology; CY Wu, YC Chiang, YJ Tai, YL Chen, HC Hsu, CA Chen, and WF Cheng: Acquisition of data ; CY Wu and WF Cheng: Analysis and interpretation of data ; CY Wu and WF Cheng: Writing the manuscript. CY Wu, YC Chiang, IL Shih, YJ Tai, YL Chen, HC Hsu, CA Chen, and WF Cheng: Review and revision of the manuscript.Figure S1Click here for additional data file.Table S1Click here for additional data file.Table S2Click here for additional data file.