Patients in the non-ASP units more frequently received unnecessary antibiotics  and, as surgical prophylaxis, the use of antibiotics not recommended by the guidelines . Multivariable analysis of the factors associated with prescriptive appropriateness identified ASP units (p = 0.02) and bloodstream or cardiovascular infections (p = 0.03) as independent predictors of better prescriptive appropriateness. The findings of the present study reinforce the importance of adopting an educational ASP to improve the quality of antimicrobial prescription in clinical practice.To evaluate the effect that an education-based Antimicrobial stewardship program (ASP) implemented in two hospitals in southern Italy had on the quality and appropriateness of antibiotic prescription. We conducted a multicenter observational study in two hospitals in the Campania region. Only some departments of both hospitals were already participating in the ASP. We collected data on all patients admitted on the day of evaluation in antibiotic therapy or prophylaxis through a case report form. The primary outcome was to investigate the difference in the appropriateness of the antibiotic prescriptive practice in the departments that had joined the ASP and in those that had not participated in the project (non-ASP). The total number of patients assessed was 486. Of these, 78 (16.05%) were in antibiotic prophylaxis and 130 (26.7%) in antibiotic therapy. The prescriptive appropriateness was better in the units that had joined ASP than in those that had not, with respectively 65.8% versus 22.7% ( Antimicrobial resistance is one of the greatest threats to global health today, leading to increased mortality, higher medical costs and prolonged hospital stays . The numAlthough antimicrobial agents used to treat infections are lifesaving, their overuse is one of the main drivers of antimicrobial resistance, resulting in the increased emergence and spread of multidrug-resistant bacteria. In hospitals the proportion of broad-spectrum antimicrobials used varied from 16% to 62% across Europe . These dTo improve antibiotic prescriptions in the hospital setting is of utmost importance to avoid heading into a post-antibiotic era, where common infections and minor injuries can once again kill . Thus, tThe objectives of the present study were to provide a snapshot analysis of antibiotic use and to investigate the impact of an educational antimicrobial stewardship program (ASP) on the appropriateness of antibiotic prescribing in two hospitals in southern Italy, in order to identify priority areas of intervention and implement measures aimed at optimizing antibiotic prescribing.This study was carried out in two hospitals in Naples and Caserta, in the Campania region of southern Italy. The 268-bed teaching hospital located in Naples serves adults and pediatrics in 30 units; the community hospital in Caserta has about 486 active beds in 23 units. Only the latter is equipped with an emergency department.A persuasive-educational ASP, based on audit and feedback conducted by a team of infectious disease consultants , was staThe present study was prospectively planned by the infectious disease consultants of the ASPs and by the healthcare administration of the two hospitals that approved and institutionalized the ASP. They prepared the study protocol in September 2019 and a pre-formed case report form. The team of infectious disease consultants at both hospitals received the same training and education on local and international infectious guidelines to follow. They also were trained with the same methodology in conducting the ASP.Thus, the snapshot analysis of antibiotic use and the evaluations of appropriateness of antibiotic prescribing were performed by audit in the two hospitals, respectively, in the week 10–14 of February 2020 in Naples, and 14–23 of November 2019 in Caserta. The audits in Naples were performed by infectious disease consultants operating in Caserta, and the audits in Caserta by those operating in Naples; the consultants were unaware if the units were participating in the ASP or not.The pre-formed case report form was filled-in on the days of evaluation by the infectious disease consultants to assess antibiotic prescriptive appropriateness, both in the units that had joined the ASP and in those that had not participated in the project.The data collected included the following: type of unit, number of patients admitted to the ward in empiric or targeted antibiotic therapy and/or antibiotic prophylaxis . For each antibiotic prescription the appropriateness in relation to the patient’s clinical state and guidelines was evaluated. We included all types of antimicrobials in the evaluation: antibacterials and antifungals for systemic use, antituberculosis, antiprotozoal and antimalarials and antivirals for systemic use. We did not include topical antibiotics.For each patient in antibiotic therapy additional data were collected. They included the type of acquisition of infection . Precisely, treatment was defined adequate if it was active towards the pathogen responsible for infection and if it was correct in dosage, duration and way of administration ,13. A thFor every antibiotic prescription deemed inappropriate, the reason for inappropriateness was recorded. Only one reason for inadequacy was enough to consider the treatment as inadequate, and it could be considered inadequate for several reasons at the same time. The antibiotic was considered unnecessary when the patient’s clinical state did not show evidence of infection. Antimicrobial therapy was considered inadequate when not indicated by the guidelines or when the antibiotic had no activity on the etiology involved .Antimicrobial therapy was considered not recommended when, in the targeted treatment, the antibiotic was active but had an excessively wide range of action for the expected etiologies or, in the case of empirical treatment, it was not recommended by the guidelines. The duration of antimicrobial therapy was considered excessive when it exceeded the recommended limits of the international guidelines.The primary outcome was to assess the appropriateness of antibiotic prescribing in the two hospitals; in particular, to assess whether there was a difference in the adequacy of prescriptive practice in the departments that had joined the ASP and in those that had not participated in the project.The secondary outcome was to identify the main reasons for prescriptive inappropriateness in order to identify priority areas of intervention and put in place measures to optimize antibiotic prescribing.All methods used in the study were in accordance with the international guidelines, with the standards on human experimentation of the Ethics Committee of the Azienda Ospedaliera Universitaria, University of Campania, and with the Helsinki Declaration of 1975, revised in 2013. Since the leadership of the University of Campania and AORN Caserta formally approved the study, and the data were collected in the aggregate manner during routine clinical activities, no approval was required by the local Ethics Committee.t-test; categorical variables were compared by the chi-square test, using exact procedures if needed.Continuous variables were summarized as mean and standard deviation, and categorical variables as absolute and relative frequencies. For continuous variables, the differences were evaluated by the Student p value < 0.1 were chosen for inclusion in an exploratory multivariable analysis, which was performed using logistic regression.Variables with a univariate A total of 53 units, between the two hospitals, were assessed; in particular, 19 medical, 25 surgical and 9 ICUs were evaluated. Of the total number of units evaluated 15 had joined the ASP and 38 had not. The total number of patients assessed was 486. Of these, 208 (42.8%) were being treated with antibiotics, specifically 78 (16.1%) were in antibiotic prophylaxis and 130 (26.7%) in antibiotic therapy.The global adequacy of antimicrobial prescription and a comparative analysis between the wards that had joined the ASP units and those that had not (non-ASP units) are summarized in p < 0.01). The inappropriateness was more frequently due to unnecessary (38.7%) or not recommended prescriptions (35.6%) or excessive duration (31%) in non-ASP units, while inadequate antibiotic prescription (21.4%) or dosing (28.6%) was more frequent in the ASP group, although the difference was not statistically significant. Patients in the non-ASP units were more frequently treated with third-generation cephalosporins  and quinolones  (p < 0.01)  . On the  < 0.01) . Only 10p < 0.01), especially in medical units  and ICUs .As shown in p < 0.01) due to the inappropriate prescription of antibiotic prophylaxis  (p < 0.01) and in the 5 patients with bacterial endocarditis (p < 0.01); instead, the 16 patients with abdominal infections were more frequently treated with inappropriate antimicrobial therapy (p < 0.01). Another factor associated with appropriate prescription was the collection of microbiology specimens (p < 0.01), while a factor associated with inappropriate prescription was the presence of nosocomial infections (p = 0.04)  . Moreove = 0.04) .p = 0.02), and bloodstream or cardiovascular (p = 0.03) as a source of infections, as independent predictors of better prescriptive appropriateness , and microbiological samples were more often collected before the start of therapy ; moreover, antimicrobial prescriptions were more frequently appropriate  (p = 0.03)  . Non-ASP = 0.03) .p < 0.01), whereas, in the non-ASP units the use of antibiotics not recommended by the guidelines was more frequently observed .Considering only the antibiotic prophylaxis, as reported in Antibiotic resistance is rising to dangerously high levels all over the world. Overuse and misuse of antibiotics contribute to the acquisition and spread of infections due to antibiotic-resistant bacteria. In the present study, we report the effects that an education-based ASP implemented in some units of two hospitals in the Campania region of southern Italy had on the appropriateness of antimicrobial prescription. Specifically, we observed a higher antimicrobial prescription appropriateness for both antibiotic therapy and prophylaxis in the units that joined the ASP; moreover, a significant decrease in the use of antibiotics with a high environmental impact, such as third-generation cephalosporins and quinolones, was observed in ASP units. Programs and interventions that aim at optimizing antimicrobial use, i.e., antimicrobial stewardship programs, have grown exponentially in recent years , provingASPs in hospitals have shown a positive impact, with reduced length of stay, shorter treatment duration without an increase in mortality and a reduction in colonization and infection with resistant bacteria ,16. In oWhen analyzing the reason for inappropriate prescriptions, we found a higher frequency of unnecessary (38.7%) or not recommended prescriptions (35.6%) in non-ASP units as compared to ASP units , while inadequate antibiotic prescriptions (21.4%) or dosing (28.6%) was more frequent in ASP groups, although none of these differences reached statistical significance. A commonly feared consequence of narrowing the spectrum of empirical therapy is the prescription of antibiotics that are ineffective against the clinical isolates. However, we should consider that in our study the definition of inadequate empirical therapy does not imply a lack of effectiveness against the isolated strain, but only against the totality of the potentially expected etiologies. Furthermore, we should point out that if we consider the total number of prescriptions, the rate of inadequacy is similar in non-ASP units  and in ASP units .Making accurate diagnoses is one of the main goals of the ASP. Overall, the results of the analysis of the antimicrobial therapy in ASP and non-ASP units reinforce the recommendations in pursuing the collection of culture samples before the start of therapy. In addition, we found that non-ASP units make greater use of empirical therapy at the same severity of the patient’s clinical state and more often resorted to the use of antibiotics when not necessary, i.e., the patient’s clinical state was not suggestive of infection. Indeed, we found a rate of about 50% of unnecessary antimicrobial prescription in non-ASP units.Similar data come from a study conducted in the United States in 2010–2011 that found at least 30% of antibiotics prescribed in doctors’ offices, emergency departments and hospital clinics were unnecessary .Staphylococcus aureus bacteremia [In the present study, another factor independently associated with appropriateness in antimicrobial prescription was the presence of bloodstream infections or bacterial endocarditis. These data may be associated with the infectious disease management of bacterial endocarditis and to the structured bacteremia program conducted by infectious disease specialists in ASP and non-ASP units of both hospitals. The infectious disease consultations that were provided to all patients with bloodstream infections have most probably increased the appropriateness of antibiotic prescriptions in this setting and improved the adequacy of patients’ management. In fact, some studies showed that advice from infectious disease specialists reduced inappropriate treatment and resulted in better clinical outcomes in the management of sepsis ,21 and Scteremia ,23,24.Finally, a better prescriptive appropriateness in ASP units was registered even in surgical prophylaxis. One of the strategies of ASP was to optimize surgical antibiotic prophylaxis, ensuring that timely and appropriate antibiotics are administered as recommended before surgery and limiting prolonged use of antibiotic prophylaxis once surgery is over . We founThis study has several limitations: even using a study setup that minimized bias inherent in subjective parameter estimation , the experts of infectious diseases may have had motivational biases that influenced their clinical judgment. Moreover, baseline data on the antimicrobial appropriates in wards before the beginning of ASP were not available, making it difficult to compare the outcomes before and after the intervention. Finally, the analysis on the relationship between appropriateness and experience of the physicians was not done. The strengths of our study include its multicenter design and the use of structured intervention that can easily be replicated and incorporated into clinical practice to evaluate the appropriateness of antimicrobial prescription.The findings of this study reinforce the importance of adopting an educational ASP in order to improve the quality of antimicrobial prescription in clinical practice and possibly to contribute to a reduction in the global phenomenon of antibiotic resistance. Structured and persuasive interventions aimed at improving prescriber knowledge and compliance, and at optimizing the management of complicated infections such as bacteremia, are of fundamental importance for the success of ASP programs. The efforts of future research should focus on identifying the best strategies to implement an effective stewardship program in hospital settings in order to reduce the misuse of antibiotics.


Immunoglobulin G4-related disease (IgG4-RD) is a systemic lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system. Involvement of the prostate is rare but has been reported in limited cases.A 28-year-old man of Asian descent with a history of sinusitis and priapism presented to hospital with rigors and voiding symptoms. He was diagnosed with IgG4-RD one month prior to presentation, following pathological analysis of a submandibular mass that demonstrated chronic sclerosing sialadenitis. On presentation, white blood cell count, C-reactive protein, and prostate serum antigen levels were all within normal limits. Examination was notable for a large, firm prostate, and a foley catheter was inserted. Contrast CT of the abdomen was unremarkable. Further workup revealed elevated serum IgG4 levels (9.22 g/L) and he was subsequently started on prednisone 35 mg daily. Imaging to screen for systemic IgG4-RD involvement demonstrated paravertebral soft tissue involvement and he was given rituximab 1000 mg IV × 2 doses. MRI revealed diffuse prostatitis. Five days after starting prednisone and one day after his first dose of rituximab, he successfully passed trial of void and was discharged home.IgG4-related prostatitis is a rare and underrecognized manifestation of IgG4-RD. Our case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals. Resolution of symptoms following treatment with steroids may be diagnostic of IgG4-related prostatitis, and may potentially avoid the need for invasive diagnostic procedures such as prostate biopsy. Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated lymphoproliferative disorder characterized by elevated serum IgG4 levels and tumefactive lesions that can involve nearly every organ system , 2. HistIn 2019, the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) proposed a three-step classification system for the diagnosis of IgG4-RD . A case Although IgG4-RD may affect nearly every organ system, genitourinary involvement is less commonly reported and typically manifests as retroperitoneal fibrosis . InvolveA previously healthy, 28-year-old man of Asian ethnicity presented to hospital with rigors and worsening voiding symptoms, including hesitancy, straining, and slow stream. One month prior to his presentation, he underwent surgical excision of a left-sided submandibular mass noted 1 year earlier. Initial biopsy of the left-sided submandibular mass revealed a 2.4 cm nodule with pathological features of reactive follicular lymphoid hyperplasia and no evidence of lymphoma. Resection of the mass was complicated by a postsurgical abscess two weeks later for which he required admission to hospital for drainage and antibiotic therapy with IV ceftriaxone and metronidazole. Pathological analysis of the nodule demonstrated chronic sclerosing sialadenitis with many areas showing greater than 100 IgG4-positive plasma cells per high-power field  scan of the abdomen demonstrated no stones or hydronephrosis, but a minimally enlarged prostate at 31 mm was noted. There was no evidence of retroperitoneal fibrosis. Subsequent tests for HIV, syphilis, gonorrhea, and chlamydia were negative, and prostate serum antigen (PSA) was normal at 0.77 µg/L. The patient was admitted to internal medicine for further workup of his urinary symptoms.During his admission, he was assessed by rheumatology and hematology. Additional investigations revealed an elevated serum IgG levels of 18.6 g/L (6.7–15.2 g/L) as well as elevated serum IgG4 level at 9.22 g/L (0.052–1.250 g/L). Other IgG subclasses were within normal limits. Serum protein electrophoresis (SPEP) demonstrated an uneven distribution of polyclonal immunoglobulins towards the fast gamma region, a finding consistent with elevated serum IgG4 levels. Autoantibody screen was negative and complement levels were normal. Given the pathology of his submandibular mass was positive for IgG4, he was started on treatment for IgG4-RD with prednisone 0.5 mg/kg/day (35 mg daily) on day 2 of admission.A CT chest was completed to evaluate for systemic IgG4 that demonstrated paraaortic and paravertebral soft tissue involvement at the levels of T8-12 , measuring 4.1 × 3.4 × 4.2 cm (30 cc), with evidence of diffuse prostatitis -positron emission tomography (PET) has also been used to support diagnosis of IgG4-related prostatitis as IgG4 lesions are FDG-avid [IgG4-related prostatitis is a rare manifestation of IgG4-RD first described by Yoshimura et al. in 2006 . The majFDG-avid , 20.Our case highlights the presence of polyclonal hypergammaglobulinemia as an early diagnostic indicator suggestive of IgG4-RD . Over onOur case has several novel features that may be used to facilitate diagnosis of IgG4-related prostatitis non-invasively. Our patient’s medical history was notable for a one-year history of sinusitis. Individuals with IgG4-RD often have preceding histories of allergies, commonly including rhinitis, nasal polyps, asthma, as well as eosinophilia in up to 40% , 23. FurWe report the youngest age of presentation with voiding symptoms attributable to IgG4-RD. Only one previous case by Vankadari et al. has reported a case of IgG4-related prostatitis in a 20-year-old male, however his presenting symptoms were recurring fever and abdominal pain, with no voiding symptoms . Our casOur case highlights the need to consider IgG4-related prostatitis as an etiology of urinary obstruction in young individuals and that resolution of symptoms after treatment with steroids may be diagnostic of IgG4-related prostatitis.


N-hydroxysuccinimide (NHS) as condensing agents. The obtained POSS polyamide was soluble in various highly polar solvents, and it could form a self-standing film. FT-IR, 1H NMR, and 29Si NMR analyses showed that POSS polyamide is a polymer in which POSS-A and POSS-C are linked almost linearly by amide bonds. Furthermore, the cast film obtained by heat-treating the polymer at 150 °C for 30 min exhibited excellent transparency and hard-coating (pencil scratch test: 5H) and antifogging properties .In this study, we prepared a polyhedral oligomeric silsesquioxane (POSS)-linking polyamide (POSS polyamide) by a polycondensation of ammonium-functionalized POSS (POSS-A) and carboxyl-functionalized POSS (POSS-C) in dehydrated dimethyl sulfoxide (DMSO) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and  Fogging occurs when water vapor condenses on a cold surface to form droplets large enough to scatter light. Fogging on transparent surfaces causes inconvenience in not only daily life, such as automobile windshields, eyeglasses/goggles, and bathroom mirrors but also advanced technology, such as solar cells and analytical/medical equipment. Therefore, there is a need for techniques to suppress fogging. Thus far, various antifogging materials have been developed ,2. Two sIn the first method, excellent water-repellent materials derived from the combination of nanoscale surface roughness and low surface free energy have been considered candidates for antifogging films ,4,5. How2), which exhibits a transition to superhydrophilicity after ultraviolet (UV) irradiation, is used as an antifogging film  (purity: 98%) were purchased from Tokyo Chemical Industry Co., Ltd. . HOTf (purity: 99%) was obtained from Kanto Chemical Co., Inc. . Sodium hydroxide (NaOH) (purity: 97%), NHS (purity: 95%), and potassium bromide (KBr) (purity: 99%) were purchased from Nacalai Tesque Inc. . Dimethyl sulfoxide (DMSO) (purity: 99%) and other solvents were obtained from FUJIFILM Wako Pure Chemical Co., Ltd. . The DMSO used in the preparation of POSS polyamide was simply dehydrated by adding molecular sieves 3A, which had been dried in an oven at 100 °C for over 1 day. Other reagents and solvents were used without further purification.APTMS (purity: 96%), 2-cyanoethyltriethoxysilane (CETES) (purity: 97%), EDC (purity: 98%), tetramethylsilane (TMS) (purity: 99%), and trischromium(III) , carboxyl component , and amide component   of this product was used for the determination. 1H NMR : δ 12.26–11.93 OH), δ 8.32–8.10 , δ 8.10–7.86 NH–), δ 3.06–2.92 –), δ 2.90–2.69 , δ 2.44–2.35 NH–), δ 2.32–2.13 OH),δ 1.82–1.56 , δ 1.56–1.32 –), δ 0.94–0.76 OH, –SiCH2CH2C(=O)NH–), δ 0.76–0.66 , δ 0.66–0.44 –). 29Si NMR : δ −65.27–−66.87 , δ −66.87–−69.50 , δ −69.50–−71.37 . FT-IR (KBr): 1724 cm−1 (–C(=O)OH), 1631 cm−1 (–C(=O)NH–), 1115 cm−1 (Si–O–Si).To a solution of POSS polyamide (0.025 g) in water (0.10 mL) was applied to a glass plate whose surface was polished using a cerium oxide powder. Then, the glass plate was heated on a hot plate (setting temperature: 80 °C) for 30 min to evaporate water, and then maintained in an oven at 150 °C for 30 min.An aqueous solution prepared by dissolving 1H and 29Si NMR spectra were recorded using an ECX-400 spectrometer . Thermogravimetric analyses (TGA) were performed using TGA-50 . To remove a small amount of solvent in the samples, they were first kept at 120 °C for 30 min under nitrogen flow (100 mL min−1). Then, after cooling to room temperature, they were heated to 1000 °C at a heating rate of 10 °C min−1 under nitrogen flow (100 mL min−1). The pencil hardness was measured using a pencil scratch tester  with the pencil at an angle of 45° under a 750 g loading. The pencil used was made by Mitsubishi Pencil Co., Ltd. . The lead of the pencils was ground perpendicularly to make an angle of 90° before measuring the pencil hardness each time. The water repellence of the cast films was evaluated using a water-drop contact-angle meter . The amount of water was 2.6 µL, and the water-drop contact angle taken with a CCD camera was measured using the half-angle method.The FT-IR spectra were recorded using an FT/IR-4200 spectrometer . The POSS polyamide was prepared by the polycondensation of POSS-A and POSS-C in the presence of EDC and NHS. A solution of POSS-A, POSS-C, EDC, and NHS in dehydrated DMSO was heated at ca. 80 °C for 12 h  groups was observed  suggest that an average of two amide bonds was formed in the POSS-A component, assuming that POSS-A is an octamer. Meanwhile, calculations based on the integral ratio of signals d’’ to f’’ (2.5:7.5) reveal that an average of two to three amide bonds was formed in the POSS-C component, assuming that POSS-C is a decamer. Furthermore, calculations based on the integral ratio of the signals e’’ to f’’ show that POSS-A and POSS-C components exist at a unit ratio of 47:53, which is almost the same as the feed molar ratio.In the  DMSO-d6 c, in add29Si NMR spectrum of POSS polyamide in DMSO-d6, some signals attributed to only T3 structure were observed  were dissolved in methanol, and the solutions were heated (ca. 50 °C) on trays to evaporate the methanol. Consequently, POSS-A was powdery  of POSS polyamide  and shape even after the above heat treatment  was applied on a glass plate and then heated at ca. 80 °C in an open system for 30 min to evaporate the water. The resulting cast film was further heated in an oven at 150 °C for 30 min. This cast film was highly transparent  and their mixture were investigated. Since the counterion of the POSS-A component in POSS polyamide is a chloride ion (derived from EDC), POSS-A, whose counterion is a chloride ion, was used here. The cast films of the starting materials were heat-treated at 150 °C for 30 min, the condition under which the POSS polyamide cast film exhibited both antifogging and hard-coating properties.The antifogging and hard-coating properties of the starting materials  and antifogging properties .In this study,


Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC.68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually.Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent max of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86–29.16)), followed by bone metastases (SUVmax 5.56 (0.97–15.85)), and lymph node metastases (SUVmax 3.90 (2.13–6.28)) and visceral metastases (SUVmax 3.82 (0.11–16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines.Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUV68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.Targeting c-MET expression,  Renal cell carcinoma (RCC) is the most common kidney cancer with more than 330,000 cases diagnosed and more than 140,000 deaths worldwide every year .The receptor tyrosine kinase c-MET regulates cell growth and differentiation as well as basic tumor pathobiology like tumor development, tumor angiogenesis, and tumor dissemination for a range of malignancies such as renal cell carcinoma –8. GibneCabozantinib is an oral small-molecule inhibitor of tyrosine kinases (TKI) including c-MET that leads to a significantly longer progression-free and overall survival in patients with metastatic RCC (mRCC) that have progressed after VEGFR-targeted therapies , 12, 13.18F-fluoro-2-deoxy-2-d-glucose (18F-FDG) for positron emission tomography (PET) and hybrid PET imaging is of limited diagnostic yield due to low 18F-FDG-avidity of RCC lesions. Therefore, 18F-FDG-PET is not recommended by practice guidelines for RCC imaging [Unlike in most other malignancies, the application of  imaging , 15. Pro imaging –21.68Ga-EMP-100 is a novel PET ligand based on a c-Met binding peptide (cMBP) already used in EMI-137, a clinical stage optical imaging agent. The affinity and specificity of the c-Met peptide as well as the conjugates was verified for human c-Met by fluorescence polarization .68Ga-EMP-100, EMI-137, has already been translated to clinic and comes with thoroughly documented pharmacokinetics [68Ga-EMP-100 which targets c-MET expression in penile squamous cell carcinoma patients [In addition, the cMBP was shown not competing with the native ligand and does not have a pharmacological effect on the HGF/c-Met signaling pathway either. The absence of pharmacological effect was confirmed by the absence of inhibition/activation of the receptor by the cMBP in HGF-induced proliferation assays; the absence of phosphorylation of c-Met tyrosine was observed at positions required for receptor activation, the absence of effect on tyrosine kinase activity and the phosphorylation of c-Met by HGF. Furthermore, the specificity of the peptide was demonstrated by the absence of significant affinity on a range of selective, central, and peripheral therapeutically relevant targets . The fluorescent analogue of kinetics , 23. Recpatients .18F-FDG-PET/CT for imaging in mRCC, and the clinical need to predict therapy success in patients on therapy with cabozantinib; in the sense of therapy individualization, mRCC seems particularly suitable for c-MET imaging.Hence, we hypothesized that a radioligand which directly targets c-MET could be used for the pretherapeutic estimation of c-MET expression prior to TKI therapies in mRCC, allowing for the assessment of the intra- and inter-individual heterogeneity of c-MET expression: due to the high c-MET expression in mRCC, the lack of suitability of 68Ga-EMP-100 PET targeting c-MET peptide in mRCC patients to assess the biodistribution and intra- and inter-individual 68Ga-EMP-100 uptake in metastatic lesions compared to physiological uptake.Here, we present the first in-human data of 68Ga-EMP-100 PET/CT. All patients gave written informed consent to undergo 68Ga-EMP-100 PET/CT according to the regulations of the German Pharmaceuticals Act §13(2b) and were referred for imaging by their treating urologist. There was no need for the patients to be fasting. This analysis was performed in compliance with the principles of the Declaration of Helsinki and its subsequent amendments [We evaluated 12 patients with mRCC who underwent endments , and ret68Ga3+ obtained from a 68Ge/68Ga generator system  was done by a simple manual synthesis under LAF conditions. Briefly, 100 μL of a stock solution of DOTA-c-MET peptide (peptide content in ultrapure water: 1 μg/μL = 0.27 nmol/μL) was mixed with 100 μL of a 3 M NaOAc). To this solution, in a 3-mL conical vial, 2 mL of 68Ga-eluate was added ; this labeling solution has a pH between 3.7 and 4.0. Then, the vial was heated in a heating block for 15 min at 95 °C. After 5 min of cooling, the reaction solution was taken up in a mixture of 1 mL ethanol, 1 mL phosphate buffer , and 5.8 mL water for injection  and sterile-filtered . If the labeling yield was too low, the labeling solution was then purified using a C18 cartridge . For this purpose, the reaction mixture was taken up after heating and applied to a C18 light cartridge; the vial was rinsed with 2 mL WFI and applied to the cartridge. After rinsing with 1 mL WFI, the labeled peptide was eluted with ethanol and water (1:1); after dilution with 7 mL WFI and 1 mL phosphate buffer, sterile filtration was performed. The labeling yields were between 82 and 98% , and the radiochemical purity was at least 96% for all products as confirmed by radio high-performance liquid chromatography.The radiolabeling of EMP100 with A mean activity of 202 ± 69 MBq was injected intravenously. Additionally, the patients were premedicated with furosemide (20 mg) for radiation protection and to reduce urinary activity in the renal pelvicalyceal system if no medical contraindication was given .PET was performed using a Biograph 64 PET/CT scanner . Approximately 60 min after tracer injection, the PET scan was initiated (2.5 min per bed position). The acquisition time was chosen based on pharmacokinetic data obtained in animal models (unpublished). For attenuation correction, a low-dose CT without contrast agent was acquired. Images were reconstructed iteratively using TrueX  with Gaussian post-reconstruction smoothing .68Ga-EMP-100 PET/CT for staging purposes as part of the clinical routine within a mean time of 11 ± 9 days prior to 68Ga-EMP-100 PET/CT imaging.All patients underwent a diagnostic, contrast-enhanced CT prior to max and SUVmean measurement.Image analysis was performed using a dedicated software package . Biodistribution and tumor uptake in patients were calculated by SUVOrgan uptake was evaluated by placing spherical volumes of interests (VOIs) inside the normal, not affected organ parenchyma using a 1-cm-diameter VOI for small organs  and a 2-cm-diameter VOI for the muscle, liver, spleen, kidney, fat tissue, aortic lumen (descending aorta), lung, bone (femur), urinary bladder content, uterus, prostate, pancreas body, small intestine, and colon.max was automatically generated around tumor lesions with focally increased tracer uptake whenever applicable. In case of close vicinity to areas with high physiological uptake or visually PET-negative lesions, a 1-cm or 2-cm spherical VOI was applied for quantification to exclude high physiological tracer excretion and to ensure reliable quantification of visually negative lesions.In a first step, a visual analysis was performed; tumor lesions/metastatic sites on CT were rated visually as being either PET-avid or PET-negative by two experienced nuclear medicine physicians and two experienced radiologists. For PET quantification of tumor sites, VOI with a 50% isocontour threshold of the SUVmax and the SUVmean of all tumor lesions by the respective SUVmean of the liver, the spleen, and the arterial blood pool.Then, tumor-to-liver ratio (TLR), tumor-to-spleen ratio (TSR) and tumor-to blood pool ratio (as derived from the aorta descendens) (TBR) were calculated by dividing the SUVTo ensure a reliable PET quantification, small lung metastases with a SAD ≤ 0.5 cm were not included in the PET quantification analysis but reported as CT findings. In the presence of disseminated hepatic or pulmonary tumor burden, a maximum of five sites in both the PET and CT components was chosen.mean, SUVmax, TLR, TSR, and TBR between different tumor localizations. A post hoc analysis from Kruskal–Wallis testing was applied to assess differences between tumor sites; here, a Bonferroni correction was applied to counteract multiple testing. A two-tailed p-value < 0.05 was considered statistically significant.Data analysis was performed using Microsoft Excel  and SPSS software v. 26 . Descriptive statistics are displayed as median (range) or mean ± standard deviation (SD). Kruskal–Wallis test for unpaired samples was used to determine differences of SUV68Ga-EMP-100 PET/CT at our department. One patient did not receive any local or systemic therapy prior to PET/CT, one patient underwent a single irradiation of an osteolytic metastasis in the right pelvis, while the other 10 patients underwent different systemic therapies and/or different kind of local therapies  years presented for 8.8–85.1 mean and SUVmax was performed in the static images 1 h after injection of the radiopharmaceutical. The highest SUVmax and SUVmean for 68Ga-EMP-100 PET were noted in the urinary bladder content, the kidneys, the liver, and the spleen. Lower SUVmax and SUVmean were exemplarily observed in the pancreas body, in the small intestine and colon, and in the parotid gland. An extended overview can be found in Table Calculation of SUV6/12 (50.0%) patients had the primary tumor in situ; of these, 2/6 (33.3%) patients additionally had tumor extension into the inferior vena cava. Lymph node metastases were observed in 7/12 (58.3%) patients, visceral metastases in 7/12 (58.3%) patients, and bone metastases in 7/12 patients (58.3%).max of 4.4 (0.1–29.2) and a median SUVmean of 2.5 (0.1–19.1). Reporting relative quantitative values, there was a median TLRmax of 1.0 (0.1–5.5) and a median TLRmean of 0.7 (0.1–3.6). In relation to the spleen and blood pool, there was a median TSRmax of 1.7 (0.2–14.0), a median TSRmean of 0.9 (0.0–6.3), a median TBRmax of 2.1 (0.3–14.4), and a median TBRmean of 1.2 (0.2–6.0).Overall, 87 tumor lesions in 12 patients were included; among these, 8/87 (9.2%) were local tumors at the primary site and/or an infiltration of the tumor in the vena cava inferior, 20/87 (23.0%) were lymph node metastases, 39/87 (44.8%) were visceral metastases, and 20/87 (23.0%) were bone metastases. 69/87 (79.3%) were rated visually as c-MET-positive. Overall, there was a median SUVmax of 9.1 (4.9–29.2), a SUVmean of 5.8 (2.2–19.1), a TLRmax of 3.9 (0.4–5.5), and a TLRmean of 2.2 (0.4–3.6). The median TSRmax was 5.0 (0.5–14.0), the TSRmean was 3.3 (0.5–6.3), the median TBRmax was 3.8 (1.4–14.4), and the median TBRmean was 2.5 (1.2–6.0). There was a heterogeneous tumoral PET-avidity in all the local tumor lesions  patients had a primary renal tumor in situ with a median SUVmax of 3.9 (2.1–6.3) and a SUVmean of 3.2 (0.7–5.0), a TLRmax of 1.0 (0.5–2.2), and a TLRmean of 0.7 (0.3–31.0). The median TSRmax was 1.0 (0.7–7.0), the TSRmean was 0.7 (0.6–2.8), the TBRmax was 2.5 (1.1–7.2), and the TBRmean was 1.8 (0.6–2.8)  patients, lymph nodes metastases were observed. In this group, lymph node metastases comprised a median SUV% patientmax of 3.8 (0.1–16.2) and median SUVmean of 2.0 (0.1–15.1), the median TLRmax was 0.9 (0.1–3.1), and the TLRmean was 0.5 (0.1–1.5). The median TSRmax was 1.3 (0.2–10.0), the median TSRmean was 0.7 (0.1–5.0), the median TBRmax was 1.6 (0.3–10.2), and the median TBRmean was 1.0. (0.2–5.1)  patients, visceral metastases were noted. Visceral metastases showed a median SUV% patientmax of 5.6 (1.0–15.9), a median SUVmean of 2.9 (0.8–7.5), TLRmax of 1.0 (0.1–3.0), and TLRmean of 0.7 (0.2–1.5). The median TSRmax was 2.1 (0.4–5.9), TSRmean was 1.1 (0.0–4.9), TBRmax was 2.1 (0.3–7.0), and TBRmean 1.1 (0.3–5.0)  patients comprised bone metastases. Among bone metastases, there was a median SUV% patientmax 9.1 vs. 5.6 vs. 3.9 vs. 3.8, p = 0.001). Evaluating all quantitative parameters , the significantly highest uptake characteristics were found in tumors at the primary site. For further specifications, see also Table The highest uptake intensity was seen in the primary tumor followed by bone metastases, lymph node metastases, and visceral metastases, e.g., median SUVPET-negative tumor lesions with a distinct CT-morphological correlate could be observed in 6/12 (50.0%) patients. From a total amount of 87 tumor lesions defined by CT criteria , 18/87  and compared the lesion uptake to the physiological uptake of liver, spleen, and blood pool. The highest physiological 68Ga-EMP-100 accumulation was detected inside the urinary bladder content. The high kidney uptake and the high liver uptake were most likely due to the unspecific accumulation of 68Ga-EMP-100. The spleen also had a moderately high 68Ga-EMP-100 uptake. Lower physiological uptake was seen in the small intestine, the colon, the pancreas, and the adrenal glands.We evaluated the physiological biodistribution of 68Ga-EMP-100 in tumoral lesions was distinctly elevated in most of the lesions; however, given the partial renal excretion of this radioligand, a certain contribution of physiological excretion to the uptake characteristics of the tumoral masses of the primary sites has to be discussed. However, visually and quantitatively, we observed higher inter- and intra-patient uptake heterogeneity when compared to other PET-ligands such as 18F-PSMA-1007 or 68Ga-DOTATOC/18F-SiTATE [68Ga-EMP-100 in both organs. Only tumor-to-blood pool (TBR) ratios appeared to be suitable for relative quantification of tumoral sites.Assessing the uptake characteristics of tumor sites, our results demonstrated a high rate of PET-positive lesions with the highest uptake intensity in tumors at the primary site. Overall, the uptake intensity of F-SiTATE , 29. The68Ga-EMP-100 compared to the surrounding tissue and the physiological uptake. The highest proportion of c-MET-negative lesions were liver and lung metastases: The high proportion of c-MET-negative lung metastases can at least be partly attributed to technical limitations  and is consistent with other tracers [We could demonstrate that the majority of tumor lesions showed a visually and quantitatively increased uptake while primary renal tumors and bone metastases showed the highest c-MET uptake. In this initial series 18/87 20.7%), lesions did not show any visually increased uptake of  tracers . On the 0.7%, lesc-MET expression in metastatic lesions was highly heterogeneous, both on an inter- and intra-individual level; however, no patient presented completely c-MET-negative since all included patients comprised at least one c-MET-avid lesion. This variety in c-MET expression could indicate the presence of clonal heterogeneity in a single patient, but also between different mRCC patients. The intra-individual heterogeneity could also possibly be a sign of (incipient) tumor dedifferentiation with a lower c-MET uptake in some RCC cells. However, we note that immunohistochemical validation after PET imaging is needed to substantiate this claim. Nonetheless, higher c-MET uptake may result in a higher rate of response to therapy with TKI which could subsequently have an impact on the clinical outcome during therapies targeting c-MET.68Ga-EMP-100 PET could be a promising approach for the evaluation of c-MET expression before choosing specific therapeutic agents, such as cabozantinib. Hence, PET imaging targeting c-MET expression using 68Ga-EMP-100 might allow a pretherapeutic estimation of treatment efficacy by non-invasive evaluation of all tumor lesions beyond the possibility of assessing the c-MET expression from a single tumor sample such as tumor resection or biopsy with the respective sampling errors in heterogeneous tumors [68Ga-EMP-100 might help identify patients who are most likely to respond to this combination therapy and might potentially serve as a predictive biomarker for patients with limited c-MET expression who should be treated otherwise. In the future, clinicopathological PET staging of c-MET expression using 68Ga-EMP-100 might also be used for monitoring changes in c-MET expression during c-MET inhibitory therapy (see Fig. Therefore, s tumors . Althougs tumors , 32, som68Ga-EMP-100 could be used in the future to assess therapeutic options with tyrosine kinase inhibitors by evaluating the extent or even existence of c-MET expression in tumor sites before anticipated systemic treatments. Moreover, this approach might be used for response assessment during systemic therapy, whereby a therapy with tyrosine kinase inhibitors is in the foreground, obviously.To sum up, 177Lu-DOTA-labeled ligands targeting c-MET which is currently being investigated. Beyond the scope of mRCC, 68Ga-EMP-100 PET could also be used in other tumor entities with known c-MET expression such as non-small cell lung cancer or differentiated thyroid cancer [Given the labeling of EMP-100 with a DOTA-chelator, a theragnostic approach might be feasible; therefore, another potential field might be the use of cMET-PET for assessment of uptake intensity before a potential therapy with d cancer .68Ga-EMP-100 uptake, has yet to be established. The potential as a new tool for risk stratification based on clinicopathological characterization with PET imaging to predict therapy response needs to be evaluated in a larger trial.A major limitation of this analysis is the retrospective design as well as the small number of patients. Further studies are needed to spatially correlate the c-MET expression with clinical follow-up as well as outcome parameters. Furthermore, in vivo and in vitro autoradiography binding studies with immunohistochemical correlation as well as preclinical studies are needed to exactly determine the c-MET expression in direct spatial correlation to the respective binding in mRCC specimens. The influence of histopathological subtypes of RCC, on the 68Ga-EMP-100 is feasible and allows for clinicopathological staging in mRCC. Our initial results warrant further studies investigating the clinical use of 68Ga-EMP-100 and its potential as a predictive biomarker of response to targeted therapies and outcome parameters.Visualization of c-MET expression with


Multi-objective optimization was performed and validated with less than 5% error between the predicted and experimental responses.Waste tire and fly ash (FA) are two waste materials whose disposal and rapid rate of accumulation are among the pressing sources of concern and threat to the environment. Although much research exists on the use of these materials in cementitious composites, very little literature is available on the effectiveness of combining them in high volumes for concrete production. This work aimed to utilize crumb rubber (CR) from waste tires as a partial replacement of fine aggregate at 15%, 22.25%, and 30% by volume, and high-volume fly ash (HVFA) replacement of cement at 50%, 60%, and 70%  to produce high-volume fly ash–crumb rubber concrete (HVFA–CRC). Using the central composite design (CCD) option of the response surface methodology (RSM), 13 mixes were produced with different combinations and levels of the CR and FA (the input factors) on which the responses of interest  were experimentally investigated. Furthermore, the composite influence of CR and HVFA on the workability of the concrete was assessed using the slump test. The results showed a decline in the mechanical properties with increasing replacement levels of the CR and HVFA. However, up to 22.25% and 60% of CR and HVFA replacements, respectively, produced a structural HVFA–CRC with a compressive strength of more than 20 MPa at 28 days. Response predictive models were developed and validated using ANOVA at a 95% confidence level. The models had high R To achieve the noble aim of environmental sustainability, governments and other relevant organizations are increasingly focused on finding more efficient ways of curtailing the depletion and degradation of natural resources. One such measure is controlling the amount of waste generation and disposal. Waste tire generation and disposal are among the most pressing environmental challenges that need to be addressed. The world is experiencing a rapid increase in automobile production to cope with the rising population and transportation needs . This le2 emissions and cost of concrete production due to excessive cement use [Another threat to the environment is fly ash (FA) generation. FA is a byproduct of coal combustion from power plants , which iment use ,17.Although the use of CR and FA in concrete has evolved for more than three decades, combining these two green materials in concrete has not been thoroughly investigated. This is evident from the scanty literature available on the topic. The earliest literature available on combined FA and CR in concrete was by Hilal . He inveAl-Fakih et al.  developeIt is obvious from the above that not much work has been done on the use of HVFA together with CR in concrete. More work in the area of engineered cementitious composite (ECC) and geopolymer concrete utilizing HVFA and CR are available than in structural concrete. This research aimed to assess the properties of a green HVFA–CRC that was produced using a high amount of waste materials (CR and FA) for environmental sustainability and cost reduction. The experiment involved the RSM tool to model and optimize the input factors (CR and FA) to yield a concrete of desirable quality in fresh and hardened states. This research will be the first to utilize HVFA and CR as replacements of cement and fine aggregate, respectively, and develop response predictive models of the mechanical properties of the composite using the RSM tool. The significance of this research lies in the potential solution to the environmental degradation caused by waste tires and FA generation and disposal, as well as the depletion of the natural raw materials.2/kg, a loss on ignition (LOI) of 1.85, and satisfying the specifications of ASTM C618 was used for cement replacement at 50, 60, and 70% by weight of total binder content. Type I ordinary Portland cement (OPC) satisfying the specifications of ASTM C150 and with a specific gravity of 3.16 was used. Low calcium FA having a specific gravity of 2.38, a specific surface area of 380 mUsing the RSM to achieve the aim of this research, the two independent variables (input factors) that were considered were the CR and FA at three replacement levels of 15, 22.25, and 30% of fine aggregate and 50, 60, and 70% of cement, respectively. Thirteen experimental runs were generated using the rotatable central composite design (CCD) option of RSM. As shown in In order to produce concrete with significant mechanical strength, the quantities of materials required for M50 concrete were adopted from Soutsos et al. . Hence, The samples were made from well-mixed HVFA–CRC that was prepared following the specifications of BS 1881: Part 125:1986. The fine aggregate, coarse aggregate, and CR were dry-mixed for 25 s in a concrete mixer. Half of the mixing water was then added and mixed for 1 min. This was followed by adding the cement and FA and mixing for 1 min. The remaining water was added and mixed until the fresh HVFA–CRC looked homogenous and consistent. To ensure the uniformity of the mix, further mixing was done manually using a hand trowel.The fresh concrete was cast into molds for the relevant test samples. Lightly oiled steel molds were used for casting the samples to allow for easy demolding. For the compressive strength test, 100 mm cube samples were cast. Beam prisms with dimensions 500 mm × 100 mm × 100 mm were cast for the flexural test and 300 mm height by 150 mm ø cylinder samples were made for the splitting tensile strength test. The samples were left for 24 h before demolding, labeled, and cured in water at 20 °C and 95% relative humidity for the required number of days.The test was performed following the requirements of BS EN 12350-2: 2009 using a slump cone with upper and lower opening diameters of 100 mm and 200 mm, respectively. The cone was filled with the concrete in three layers and compacted using a 16 mm diameter, 600 mm long tamping rod by tamping the concrete 25 times. The mold was removed and the height difference between the cone and the slumped concrete was recorded as the slump of the concrete, as shown in The compressive strength (CS) test was performed based on the specifications of BS EN 12390-3:2019 at 7, 14, and 28 days of curing. The samples were tested by subjecting them to a uniaxial compressive load by means of a 3000 kN universal testing machine (UTM), as shown in A three-point flexural test was conducted following the specifications of BS EN 12390-5:2019 using a 200 kN UTM, as shown in The splitting tensile test was performed using a 3000 KN UTM in accordance with the provisions of BS EN 12390-6:2019, as shown in The slump test result is shown in The enhanced workability with increasing FA replacement was due to the spherical morphology of the FA particles. The nature of the FA particles is shown in the FESEM image in On the other hand, the workability of the HVFA–CRC mixes reduced with increasing CR replacement. This was observed from the slump for mixes with the same FA content but different CR content. RUN3  had a 16.6% and 50% lower slump compared with RUN5  and RUN1 , respectively. This trend was observed across all mixes with the same FA content but different CR content. The negative influence of the CR on the workability of cement composites has been reported by previous researchers, such as Assaggaf et al.  and SiddThe slump for all the 13 mixes ranged from 20–45 mm, which were classified under the “very low” to “low” workability categories. The three mixes  in the “low workability” class had 70% FA, while the rest of the mixes fell into the “very low workability” class. The low slump was due to the low W/B (0.40) and the absence of a superplasticizer in the mix. As stated earlier, the low W/B was used to achieve a high concrete strength. The workability of the mixes can be greatly enhanced if a superplasticizer is used, as reported from previous research on CRC [2 produced from the cement hydration to form secondary C-S-H gel in addition to the one generated during the primary cement hydration. The reaction, although slow at the beginning, goes on for a long time, leading to increased strength at later stages of the composite. This behavior is consistent with the findings of previous research on FA replacement of cement in composites [The rate of development for the compressive strength of the HVFA–CRC is shown in mposites ,11,30,31On the other hand, because strength development is a chemical process, CR does not have any influence, as it participates at a physical level. It was observed that the compressive strength of the concrete decreased with an increase in the CR replacement. The main reason behind the decrease in compressive strength with increasing CR content is due to the lack of proper bonding between the CR and the hardened cement matrix at the interface, as reported by Najim and Hall  and as dThe lower flexural strength of the concrete with increasing CR and HVFA was attributed to the similar reason stated for compressive strength. However, the enhanced ductility was attributed to (1) the flexible nature and low elastic modulus of the CR particles, which can easily bend under load, and 2) the toughness reduction effect of the FA. At 28 days, most of the HVFA remained unreacted within the composite serving as a filler, thereby refining the pore structure of the composite and enhancing the density and increasing the deformation capacity. Similar findings regarding the effect of CR in concrete have been reported in previous research  the toug. SimilarThe HVFA–CRC splitting tensile strength test result is shown in The behavior of the HVFA–CRC due to the effect of the CR and FA replacement values is shown visually using the 2D contour and 3D response surface plots in y signifies the desired response, k and The response prediction models were developed using the RSM and their adequacy was verified using analysis of variance (ANOVA). A response model can take the form of a linear or quadratic polynomial, as shown in Equations (1) and (2), respectively ,35:(1)y=The model equations (in coded terms) developed for the three responses  are presented in Equations (3)–(5). All the responses were fitted with quadratic models, as shown:where CS is the compressive strength (MPa), the flexural strength is FS (MPa), TS is the tensile strength (MPa), A is the CR replacement (%), and B is the HVFA replacement (%).2. Furthermore, AB was a significant model term for TS. To ensure the fitness of the models to the data, the lack of fit values must be insignificant [The adequacy of the developed response models was checked using ANOVA, the summary of which is presented in nificant . The lac2). The R2 is a measure of how close the data is to the fitted model. Generally speaking, the higher the R2 value , the better the model fits the data. In this case, the R2 values were 97.7%, 95.3%, and 97.3% for CS, FS, and STS, respectively, as presented in Another measure for the strength of a model is the coefficient of determination  is a method that is used to determine the optimal amount (level) of the input variables to concurrently improve two or more responses. Most real-life optimization situations involve the need to strike a balance between more than one (often conflicting) objectives . The optIn this research, the optimization criteria and the result are shown in The optimization result was experimentally validated by producing HVFA–CRC samples using the RSM-generated CR and HVFA replacements. Samples that were used to determine the CS, FS, and STS were cast, cured for 28 days, and tested. The averages of the results are shown in 1.An increase in the slump by 80–200% was observed by mixes having 50–70% HVFA content at the same CR content.2.CR affected the workability of the concrete via a 16.6–50% reduction in the slump between mixes having 15–30% CR at a 70% HVFA replacement level.3.The mechanical strengths of the concrete were negatively affected by the increase in CR and HVFA replacements. Nevertheless, a 28-day strength of more than 20 MPa was attained by many of the mixes with CR and HVFA replacements of less than 22.25 and 60%, respectively. Conversely, with higher CR and HVFA replacements, the ductility was enhanced, leading to better deflection capacity, energy absorption, and change in the failure mode from brittle to ductile.4.2 of 97.74%, 95.26%, and 97.36 for the CS, FS, and STS, respectively. Multi-objective optimization performed yielded optimal values of 15% and 50% for CR and HVFA, respectively, to achieve 28.89 MPa, 4.75 MPa, and 2.79 MPa for the CS, FS, and STS, respectively, at a desirability value of 99%. Experimental validation showed a high level of agreement between the predicted and the experimental values with a percentage error of less than 5%.Response predictive models were developed and validated with a high R5.The optimization results showed that 25.7% CR replacement of fine aggregate and 58.6% HVFA replacement of cement were the optimal values of the input factors that will produce HVFA–CRC that is suitable for structural applications.The following conclusions were drawn at the end of the research:The utilization of high amounts of CR and HVFA together to make the structural concrete produced in this work is a positive result that can help in tackling the waste disposal and environmental degradation problems, which will lead to achieving environmental sustainability. However, the models were developed for a low calcium class F FA and CR that had the properties specified in this research work. Any deviation from the materials’ properties may lead to an inaccurate response prediction.


Polymer-modified concrete and fiber concrete are two excellent paving materials that improve the performance of some concrete, but the performance of single application material is still limited. In this paper, polymer-modified concrete with strong deformation and fiber concrete with obvious crack resistance and reinforcement effect were compounded by using the idea of composite material design so as to obtain a high-performance pavement material. The basic mechanical properties of high-content hybrid fiber–polymer-modified concrete, such as workability, compression, flexural resistance, and environmental durability (such as sulfate resistance) were studied by using the test regulations of cement concrete in China. The main results were as follows. (1) The hybrid fiber–polymer concrete displayed reliable working performance, high stiffness, and a modulus of elasticity as high as 35.93 GPa. (2) The hybrid fiber–polymer concrete had a compressive strength of 52.82 MPa, which was 31.2% higher than that of the plain C40 concrete (40.25 MPa); the strength of bending of the hybrid concrete was 11.51 MPa, 191.4% higher than that of the plain concrete (3.95 MPa). (3) The corrosion resistance value of the hybrid fiber–polymer concrete was 81.31%, indicating its adjustability to sulfate attack environments. (4) According to cross-sectional scanning electron microscope (SEM) images, the hybrid fiber–polymer concrete was seemingly more integrated with a dense layer of cementing substance on its surface along with fewer microholes and microcracks as when compared to the ordinary concrete. The research showed that hybrid fiber–polymer concrete had superior strength and environmental erosion resistance and was a pavement material with superior mechanical properties. Polymer-modified cement concrete is a composite material formed by the addition of water-soluble organic polymer to cement concrete. The polymer demulsifies within the concrete structure to form a film and fills in the concrete voids, forming a structural network with the hydration products of the cement, which in turn alters the internal concrete microstructure. When compared with ordinary cement concrete, the deformation performance, bending resistance, durability, and impermeability are improved ,2,3,4,5.Steel fiber-reinforced concrete can significantly improve the bending-tensile performance, crack resistance, durability, and fatigue performance of the component structures ,9,10,11 The use of fibers as mass reinforcement to delay cracking and to improve the strength and the postcracking performance of reinforced concrete (RC) beams has been well documented . Ultra-hCompared to ordinary concrete, polymer-modified cement concrete has shown better deformability, cohesion, durability, wear resistance, and impermeability and is widely used. However, it is burdened by high polymer price, relatively complex construction process, and slightly insufficient mechanical indexes in areas such as bending-tensile strength, impact resistance, and toughness when used for certain special pavements. Steel fiber-reinforced concrete, on the other hand, shows excellent toughness, bending-tensile resistance, impact resistance, fatigue resistance, and durability, but has inadequate adhesion between the steel fiber and the concrete . Therefore, steel fiber-reinforced concrete is not utilized to its full potential. In addition, its deformation performance and wear resistance remain insufficient for special paving ,22,23,24This study presents the author’s systematic results. A large number of experiments were carried out in the early stage. The aim of this research was to create high-content fiber concrete with uniform dispersion. The uniformity of fiber concrete directly affects the performance of materials. In order to achieve uniform distribution, polymer materials were introduced in this work. The addition of polymer materials actually enabled the uniform distribution of high content fibers. Based on previous exploration, this research found that the addition of some polymers can significantly change the workability of concrete so as to improve the maximum content of fiber. Therefore, in this study, hybrid fiber–polymer concrete with high fiber content was created. When polymer emulsion and steel fiber of a certain proportion were mixed into the concrete, the emulsion formed a network structure on the surface of the steel fiber and the aggregates of the mixing process, which reduced the concentration of stress and enhanced the adhesion between the steel fiber and the aggregate. Therefore, the properties of toughness, density, crack resistance, and fatigue resistance for the whole material were improved.The material studied in this paper had high mechanical properties and durability. It is expected to be used on special occasions with high performance requirements, such as steel bridge deck pavement, factory roads in harsh environments, etc.The characteristic parameters and sources of procurement of the raw materials were as follows.Cement: Ordinary 42.5 silicate type Huaxin Cement produced in Chongqing, as shown in Gravel: Locally produced cobblestones from Chongqing with a maximum nominal grain size of 10 mm and a grading of 5–10 mm, as shown in Fly ash: Grade I fly ash locally produced in Chongqing, as shown in Ordinary steel fiber: Sheared wavy steel fiber  with length of 35 mm and diameter of 0.87 mm, as shown in Ultrashort ultrafine steel fiber: Melted and drawn ultrashort ultrafine steel fiber manufactured by Liaoning Anshan Kebite Technology Co., Ltd. with length of 6 mm and diameter of 0.2 mm, as shown in Flexible fiber: Polypropylene flexible fiber with length of 12 mm , as shown in Polymer emulsion: Independently developed polymerized compound emulsion, as shown in After the preparation of the trials, the ratios of volume of the ordinary steel fiber, the ultrashort ultrafine steel fiber, and the flexible fiber (polypropylene fiber) were determined to be 1.92%, 4.00%, and 0.27%, respectively. The unit cubic mass mix proportion used in this study was as follows: cement (42.5 ordinary silicate cement)/fly ash/gravel (granite)/medium–coarse sand/ordinary steel fiber/ultrashort ultrafine steel fiber/polypropylene fiber/polymer emulsion = 580:250:600:600:150:312:3:320 kg.Slump is mainly used to characterize the plasticizing and pumpable performance of concrete, and the requirements for application to different structures are different. This paper aimed to investigate a material for application to some special pavement structures, such as steel bridge decks, to be used mainly by paving. Therefore, the smaller the slump, the better the paving effect and material performance were judged to be.The slump test detects the water retention, fluidity, and cohesion of the concrete matrix and also verifies the feasibility and workability of the designed mix proportion. According to the Standard for the Test Method of Performance on Ordinary Fresh Concrete (GB/T50080-2016) , the fol(1) The inside of the slump barrel was moistened with water to prevent the adhesion of the concrete mixture with the inner barrel wall, which could potentially cause bonding damage to the concrete during the falling off process. Next, the barrel was placed on a dry, horizontal plate made of steel or wood to avoid the influence of plate inclination and humidity on the test results. The slump barrel was fixed during the filling process, and both feet were stepped on the pedal for loading.(2) When the materials were loaded to 1/3 and 2/3 of the barrel height, the tamping rod was used for continuous and stable tamping around 20 to 30 times. The tamping rod penetrated the concrete composite matrix without causing an impact to avoid the dispersion of the composite. When the materials were loaded to the top of the slump barrel, then the excess mixture was scraped off with a trowel, and the top surface was smoothened with a scraper.(3) After the excess concrete materials around the bottom of the barrel were removed, the barrel was lifted within 5 to 10 s. During this period, the slump barrel was lifted vertically with a uniform speed without imposing transverse or twisting forces on the concrete. The whole process from the beginning of loading to the lifting of the slump barrel was completed within 150 s.(4) A flat plate, which came in contact with the concrete mixture but did not exert force, was gently placed on the top of the concrete mixture during the slump measurement process. The height h was measured from the plate to the bottom with a measuring scale, and then h was subtracted from the height H of the slump barrel. The result obtained was the measured slump, expressed in the unit of mm.In the slump test, four basic processes were generally included in the preparation of the concrete mixture: weighing, mixing, loading, and measuring. The measuring is shown in Standard for Test Method of Mechanical Properties on Ordinary Concrete (GB/T 50081-2002) [The test method for the elasticity modulus under static pressure was performed as specified in 81-2002) . The tesDuring the elasticity module test, the two dial gauges were installed on the fixed frame and symmetrically arranged on both sides of the sample, and the bottom of the dial gauge was close to the centerline on both sides of the test piece. The sample was placed on the central region of the platform, and the press machine was turned on to gradually lower the upper platform and ensure its balanced contact with the sample.F0. This stress was held for 60 s, and the readings of the dial gauges were recorded on both sides as 0 (left) and 0 (right). Next, the load was continuously and evenly applied with a loading rate of 0.6 MPa/s. When the load was 1/3 of the ultimate compressive strength, the load was recorded as nF and held for 60 s, and the readings of the dial gauges are recorded as n (left) and n (right). The differences between the two values and their average did not exceed 20%; if it did, the load was be applied again (the unloading and loading speeds were consistent) until the test requirement was met. It should be noted that, in practice, the same batches of specimens were selected for the compression test in advance. The compression strength of these specimens was measured to convert the load corresponding to 0.5 MPa to eliminate the support displacement. The strength formed by the corresponding load was not necessarily 0.5 MPa corresponding to the test specimen, including 1/3 ultimate compressive strength.The sample was pretested before the formal test. The loading principle was as follows. First, initial stress of 0.5 MPa was applied, which corresponded to the initial load F0 and was held for 60 s, and then the load was increased to Fn, held for another 60 s, and again unloaded to the reference load F0. This preloading cycle was repeated three times.Preloading started after the pretest was completed. Preloading started from the reference load F0, the readings of the two dial gauges were recorded as 0 (left) and 0 (right) were recorded after the load was held for 60 s. The load was increased to nF and held for 60 s, and n (left) and n (right) were recorded. Afterward, the dial gauges and fixing frames were removed, the sample was loaded at a rate of 0.6 MPa/s until its failure, and the load during failure was recorded as cpF. If the difference between this cpF and that measured in the first group was more than 20%, this was marked. The compressive elasticity modulus of the concrete was processed based on the following formula:nF is the final load imposed in the elasticity modulus test ; F0 is the initial load imposed in the elasticity modulus test ; L is the length of the measurement gauge (mm); A is the loaded area of the sample (mm2); nF and F0 at the final loading (mm), i.e., n(left)+n(right))/2−(0(left)+0(right))/2; 0 is the reading of the dial gauge when at a load of F0 (mm); and n is the reading of the dial gauge at a load of nF (mm).The formal test was conducted as follows. After the last preloading cycle, starting from the reference load This test was conducted for 3 days, 7 days, and 28 days; each duration was divided into early and late stages. The purpose of this test was to investigate the change in the compressive strength of the hybrid concrete during the starting and final stages when compared to ordinary concrete.There were 6 groups of samples, including 3 groups of hybrid fiber–polymer concretes and 3 groups of C40 plain concrete, which corresponded to the three durations. There were 3 samples in each group, and thus 18 compressive samples in total, of which all had a size of 100 mm × 100 mm × 100 mm.A fully automatic pressure testing machine in the laboratory that had a measuring range of 300 tons was used. The test was performed according to the Testing Methods of Cement and Concrete for Highway Engineering  and TestF is the ultimate load (N), and A is the loaded area (mm2). The accuracy of the calculation was 0.01 MPa.Here, The splitting tensile test and bending tensile test are indirect tensile tests. Like direct tensile tests, they can reflect the tensile properties of materials. A material’s structural design needs to consider the applicable scene and stress state of the material and the stress performance requirements of the structural pavement. This study used the bending tensile test to evaluate the tensile performance of the material under examination.In order to eliminate the effect of shear stress, four point bending is a common test method. Its advantage is that the bending moment is evenly distributed and that the test results are therefore more accurate. In the test, the three-stage method is used to determine the loading position; that is, the two loading points at the loading position can divide the distance between the supports equally so as to determine the shear and bending spans of the specifications.The bending test aimed at exploring whether the bending strength and crack resistance of the concrete were improved after the addition of the steel fiber, flexible fiber, and polymer emulsion, and if so, to what extent. The test was divided into ages of 3 days, 7 days, and 28 days to study the phase changes of strength and toughness for the hybrid concrete compared to that of ordinary concrete.Testing Methods of Cement and Concrete for Highway Engineering [Test Methods Used for Steel Fiber Reinforced Concrete [The test was performed according to the ineering  and TestConcrete  by usingAs in the compression test, there were 18 compressive samples in total, which included three groups of hybrid fiber–polymer concretes and 3 groups of C40 plain concretes, each containing 3 samples, though the sample size was 400 mm × 100 mm × 100 mm instead.F is the ultimate load (N), L is the spacing between the supports (mm), b is the sample width (mm), and h is the height of the sample (mm).When the cross-section was within the pure bending section, the bending strength was calculated from the following formula:Testing Methods of Cement and Concrete for Highway Engineering.Since the sample size (400 mm × 100 mm × 100 mm) was nonstandardized, the test result had to be multiplied by a factor of reduction of 0.85 according to the Under alternating high temperature and sulfate solution processing, shrinkage due to drying at high temperatures and expansion due to the erosion of sulfate solution cyclically occurred in the concrete. As the cycle repeated, the shrinkage and expansion of the concrete eventually led to extreme stress failure and internal cracks.This test simulated the resistance capacities of the hybrid fiber–polymer concrete and plain concrete to natural sulfate attack, in contrast to the actual background of the industrially polluted environment.Standard for Test Methods of Long-term Performance and Durability of Ordinary Concrete [This test was performed as per the Concrete . When thFor economical purposes, the sample size in this test was set to be 40 mm × 40 mm × 160 mm. A total of 12 samples were divided into two test groups and two control groups. The four-point loading mode was used in this case, though the supporting point was placed 20 mm away from the end of the sample, with a spacing of 40 mm between the loading points and a distance of 40 mm between the loading and the supporting point. The bending strength was calculated by using Equation (3), and the corrosion resistance was calculated by using:A scanning electron microscope (SEM) was used to determine the microstructural changes in ordinary concrete after the addition of polymer emulsion and steel fiber. The purpose of SEM was to explain the strength growth mechanism of the material and to explain how the fibers and concrete existed as a whole according to the observed microinterface between the fibers and concrete.Focused electron beams were used by the SEM to scan and image the sample surface point by point. During the test, the cross-section of the sample was cleaned to avoid hampering of the observation results by concrete debris. Samples generally consisted of bulk materials or powder particles, and the imaging signals included secondary electrons, backscattered electrons, or absorbed electrons. The cross spot was taken as the electron source, and a micro electron beam with a certain energy, beam intensity, and beam spot diameter was formed because of the shrinking of the secondary condenser and the objective lens. Grid scanning was performed on the surface of the sample in a certain temporal and spatial sequence, driven by the scanning coil. Physical signals such as the secondary electron emission and the backscattered electrons were produced during the interaction of the focused electron beam with the sample. The amount of secondary electron emission changed along with the surface morphology of the sample. The detector collected the secondary electron signal and converted it into an electrical signal, which was fed into the kinescope grid after video amplification. A secondary electron image reflecting the surface morphology of the sample was obtained by modulating the brightness of the kinescope that was scanned synchronously with the incident electron beam.The slump test was conducted thrice and was categorized as groups A, B, and C. Each group contained the the same mix proportion, but for more accurate data, the test was conducted three times, and the average value was taken. The measured data were collected immediately after the slump barrel was lifted and after intervals of 0.5 h, 1.0 h, 1.5 h, and 2.0 h. If hybrid fiber–polymer concrete were applied to pavement materials, to facilitate construction, it would be expected that it had good fluidity at the beginning and good plasticity after forming. Therefore, this paper tested the variation law of slump with time to examine the hybrid concrete’s working performance.Test result analysisThe three groups of test data showed very low discreteness . The conTest result0 = 11.25 kN, Fn = 332.1 kN. By feeding these data into Equation (1), the elasticity moduli A, B, and C were found to be 36.41 GPa, 32.63 GPa, and 38.75 GPa. Based on the results presented above, the elasticity modulus of the hybrid fiber–polymer concrete was found to be 35.93 GPa.In the elasticity modulus loading test, FTest result analysisFrom the test results, the elastic modulus of the hybrid fiber–polymer concrete was slightly higher than that of ordinary cement concrete, indicating that the hybrid material had high resistance to deformation. If it were applied to steel deck pavement, it would significantly increase the stiffness of the structure compared with the commonly used asphalt concrete.Test resultTest result analysisAs shown in According to the characteristics of failure displayed in Test resultTest result analysisComparative analysis of the bending test results displayed in According to the bending failure patterns revealed in In the process of preliminary exploration and research, it was found that greater numbers of steel fibers in the cross-section corresponded to a stronger bending capacity. When the total number of steel fibers was fixed, enhancing the uniform dispersion and reducing the agglomeration of the fibers effectively increased the number of steel fibers in the cross-section. As for the distribution, the bending capacity was the highest when the steel fiber in the cross-section was distributed vertically relative to the fractured surface. To a certain extent, improving the uniform dispersion of the steel fibers also facilitated optimal distribution. The force of bonding between the steel fiber and the concrete matrix depends on the cementation of the cement and the polymer emulsion colloids. The choice of cement and the types of polymer emulsion that best suit the steel fiber could further improve the bending capacity of the hybrid fiber–polymer concrete.Test resultThe load–displacement curves for the hybrid fiber–polymer concrete with and without sulfate attack were compared, as shown in Test result analysisThe bending test results of the two materials cured with and without sulfate attack  of the hybrid fiber–polymer concrete revealed favorable adaptability to sulfate environments.The SEM test demonstrated that the hybrid fiber–polymer concrete was more integrated than ordinary concrete, as it had fewer microholes and microcracks when compared with ordinary concrete. This characteristic could lead to its higher bending and compressive strengths when compared to those of ordinary concrete. SEM showed that the steel fiber and concrete were integrated by wrapping the steel fiber with a slurry, and that the slurry was a polymer–cement net formed by polymer latex and cement.


Timely recognition of warning signs from deteriorating patients and proper treatment are important in improving patient safety. In comparison to the traditional medical emergency team (MET) activation triggered by phone calls, automated activation of MET may minimize activation delays. However, limited data are available on the effects of automated activation systems on the time from derangement to MET activation and on clinical outcomes. The objective of this study was to determine the impact of an automated alert and activation system for MET on clinical outcomes in unselected hospitalized patients.This is an observational study using prospectively collected data from consecutive patients managed by the MET at a university-affiliated, tertiary hospital from March 2013 to December 2019. The automated alert system automatically calculates the Modified Early Warning Score (MEWS) and subsequently activates MET when the MEWS score is 7 or higher, which was implemented since August 2016. The outcome measures of interest including hospital mortality in patients with MEWS of 7 or higher were compared between pre-implementation and post-implementation groups of the automated alert and activation system in the primary analysis. The association between the implementation of the system and hospital mortality was evaluated with logistic regression analysis.P < 0.001). In addition, unplanned ICU admission rates  was reduced during the post-implementation period. Hospital mortality was decreased after implementation of the automated alert system . The implementation of the automated alert and activation system was associated with decreased risk of death in the multivariable analysis .Of the 7678 patients who were managed by MET during the study period, 639 patients during the pre-implementation period and 957 patients during the post-implementation period were included in the primary analysis. MET calls due to abnormal physiological variables were more common during the pre-implementation period, while MET calls due to medical staff’s worries or concern about the patient’s condition were more common during the post-implementation period. The median time from deterioration to MET activation was significantly shortened in the post-implementation period compared to the pre-implementation period (34 min vs. 60 min, After implementing an automated alert and activation system, the time from deterioration to MET activation was shortened and clinical outcomes were improved in hospitalized patients.The online version contains supplementary material available at 10.1186/s40560-021-00588-y. Hospital ward patients often show abnormal physiological signs hours before adverse events such as unexpected cardiac arrest . Timely Activation of the MET is initiated by identifying patients who are deteriorating or at risk of deterioration . The useAll consecutive patients who were managed by the MET were prospectively registered following the initiation of the MET program at Samsung Medical Center , which provides care for approximately 92,000 inpatients per year. To address the primary research question of whether implementation of an automated alert and activation system for MET is associated with clinical outcomes in hospitalized patients, we compared clinical data on patients managed by MET before and after implementing the automated alert and activation system in August 2016. The institutional review board of the Samsung Medical Center approved this study and waived the requirement for informed consent because of the observational nature of the research. Additionally, patient information was anonymized and de-identified prior to analysis.All consecutive adult patients who were managed by the MET on the general ward between March 1, 2013 and December 31, 2019 were included in the study. Some clinical data for patients enrolled between 2013 and 2018 were included in a previous study [To address the primary research objective of evaluating the effect of the automated alert and activation system with the Modified Early Warning Score (MEWS) , only paDetails of the hospital’s MET system have been described in previous publications , 15, 16.When activated, the MET is expected to arrive within 10 min, complete patient assessments within 30 min, and order diagnostic tests and therapeutic treatments relevant to the patient’s condition. After assessment and therapeutic interventions by the MET, patients who are considered to require treatment and monitoring that cannot be provided outside of the ICU are transferred to the ICU, while patients in a stable condition remain on the general ward.In August 2016, the MET initiated an active screening program for all ward patients using the automated alert and activation system based on a MEWS. The MEWS was automatically calculated using five physiological parameters  when nurses recorded the patient’s vital signs into the electronic medical record. If MEWS was 7 or higher, an automated alert was sent to MET members as a text message in real-time, 24 h a day, 7 days a week, and the MET was activated automatically. Information about the patient’s code status was recorded in the hospital electronic medical record and patients who consented to a do-not-resuscitate order were excluded from the active screening. Alerts were not displayed to physicians and nurses of the ward, but color-coded MEWS were displayed in the patient list in the electronic medical record interface. Thus, medical staff of the ward could recognize the patient’s MEWS status: green for MEWS 0–2, yellow for MEWS 3–4, orange for MEWS 5–6, and red for MEWS ≥ 7. Patient vital signs were recorded at the bedside immediately after measurement using a laptop or portable device whenever possible. The frequency of measuring vital signs was made according to the order of the attending physician without a prescribed hospital policy, but vital signs were usually measured at least four times a day and more frequently if the patient’s clinical condition changed. MEWS was automatically updated whenever a vital sign was newly recorded.Details of all MET activations triggered by call and automated alert were recorded in the specified format as soon as possible after the event by a MET member in a registry. The following information was collected and recorded: patient demographics, method that triggered MET , reasons for the MET activation based on calling criteria, time of the first documented physiological disorder, MEWS, time of the MET activation and deactivation, vital signs at the time of the MET activation and deactivation, interventions delivered by the MET, and the patient’s disposition after the clinical episode , 17. TheWhen the MET was activated by the automated alert and activation system, the physiologic derangements of the patient at the time of the MET activation were recorded as reasons for MET activation based on calling criteria with physiologic variables with specific cut-offs .Descriptive statistics were performed to compare the characteristics and clinical outcomes between the two periods before and after implementing the automated alert and activation system. Continuous variables were expressed as medians and interquartile ranges and were compared with a Mann–Whitney ff point . The impanalyses , as wellanalyses . The resDuring the study period, 7678 consecutive patients were managed by the MET. Among them, 176 patients outside of the general ward and 65 patients whose outcome data were not available were excluded. Finally, 7437 eligible patients were retrieved and 639 (18.5%) of 3457 patients during the pre-implementation period and 957 (24.1%) of 3980 patients during the post-implementation period with MEWS of 7 or higher were included in the primary analysis  and neurologic systems  were higher in the pre-implementation period, while MET calls due to concern about overall deterioration  were higher in the post-implementation period. Median MEWS scores of patients reviewed by MET during the pre-implementation and post-implementation period were 8 and 7, respectively (P = 0.001). The median time from derangement to MET activation was significantly shorter in the post-implementation period . In the post-implementation period, application of high-flow nasal cannula or non-invasive ventilation by the MET was more common. Only advice was given in more cases in the post-implementation period.The characteristics of all patients and MET activation in the pre-implementation and post-implementation periods are shown in Table P < 0.001)  and hospital length of stay  were reduced during the post-implementation period  patients in the pre-implementation period and 231 (27.2%) patients in the post-implementation period died during hospitalization (P = 0.018), fever at the time of activation , bolus fluid administration  and medication therapy during MET activation  were associated with decreased risk of death Additional file 3: Table S3. Patient clinical characteristics and MET activation in patients with MEWS < 7.