However, these cancers do eventually continue to grow after targeted therapy. In this paper, we aimed to summarize the current research identifying changes in the mesenchymal-epithelial transition (MET) gene that occur after EGFR-targeted therapy, allowing the cancer to become resistant. We summarized current medications that target MET, and early findings from trials that used medications targeting both EGFR and MET together. Targeting both mechanisms at the same time could be a promising new treatment strategy, and larger trials studying these treatments in combination are currently ongoing to understand the potential benefit to patients.In non-small cell lung cancer that has spread to other locations in the body, identifying genetic abnormalities in a patient’s cancer has allowed for the development of targeted treatments. For cancers that have genetic changes in epidermal growth factor (EGFR)-mutated cancers, EGFR inhibitors, including the third-generation tyrosine kinase inhibitor (TKI) osimertinib, significantly prolong progression-free survival and overall survival, and are the current standard of care. However, progression after EGFR inhibition invariably occurs, and further study has helped elucidate mechanisms of resistance. Abnormalities in the mesenchymal-epithelial transition (MET) oncogenic pathway have been implicated as common alterations after progression, with MET amplification as one of the most frequent mechanisms. Multiple drugs with inhibitory activity against MET, including TKIs, antibodies, and antibody–drug conjugates, have been developed and studied in advanced NSCLC. Combining MET and EGFR is a promising treatment strategy for patients found to have a MET-driven resistance mechanism. Combination TKI therapy and EGFR-MET bispecific antibodies have shown promising anti-tumor activity in early clinical trials. Future study including ongoing large-scale trials of combination EGFR-MET inhibition will help clarify if targeting this mechanism behind EGFR resistance will have meaningful clinical benefit for patients with advanced EGFR-mutated NSCLC. Utilizing targeted therapy against activating mutations has opened a new era of treatment paradigms for patients with advanced non-small cell lung cancer (NSCLC). For patients with  In patients with advanced or metastatic NSCLC, molecular testing is recommended by the National Comprehensive Cancer Network (NCCN) guidelines for established molecular biomarkers . An epided NSCLC . Exon 19e tumors . For pat of care . EGFR mutation [EGFR-positive NSCLC [First- and second-generation EGFR TKIs including erlotinib, afatinib, geftinib, and dacomitinib have inhibitory effects on EGFR. However, a common pattern seen when utilizing targeted therapy is the development of resistance to the targeted agent through additional mutations or alterations. This was seen after treatment with first- and second-generation EGFR inhibitors; resistance commonly developed through the T790M mutation . The thive NSCLC ,6. mesenchymal-epithelial transition (MET) oncogene alterations as the most common mechanism. In analyses of patients in the FLAURA trial, in EGFR-positive NSCLC treated with first-line osimertinib who progress, MET amplification can be seen in 15% of patients [MET amplification as the most frequent genetic mechanism of resistance found, identified in 16% [EGFR mutant tumors; MET amplification is also being identified in as a driver to resistance to ALK, RET, and ROS-1 fusion TKI treatment [However, despite the shifting treatment paradigm to first-line osimertinib, resistance inevitably develops. Next-line therapy for those who progress after osimertinib has typically consisted of platinum-based chemotherapy. The study of resistance mechanisms to osimertinib has revealed additional molecular targets for therapy, with patients . In an ad in 16% . Identifd in 16% . This isreatment .MET encodes for a receptor tyrosine kinase which is activated by hepatocyte growth factor (HGF), and is found primarily in epithelial cells [MET signaling activates RAS-MAPK, PI3K, and STAT3 pathways, leading to cell migration, invasion, proliferation, and cell survival [MET signaling has been seen in many types of cancers, including NSCLC, including gastric cancers, colorectal cancer, and papillary renal carcinomas [MET abnormalities occur through MET exon skipping and amplification [MET in resistance to EGFR TKIs and the development of MET targeted therapies, this has become a promising area of clinical development in the treatment of advanced NSCLC [al cells . Downstrsurvival ,12. Incrrcinomas . MET abnfication ,15. Withed NSCLC .MET, RET, BRAF, KRAS, and PI3K, as well as histologic transformation. Patients may have more than one coexisting molecular mechanism contributing to resistance [MET alterations, particularly MET amplification, have been seen as the most frequent mechanism.Further study of the genomic changes of patients who’ve progressed after treatment with osimertinib have elucidated a diverse range of mechanisms of resistance. This includes EGFR-dependent mechanisms, alterations in sistance . While tMET dysregulation most commonly occurs through amplification or exon 14 skipping mutations. Exon 14 skipping mutations are caused by a point mutation or deletion that leads to loss of exon 14. Without exon 14 appropriately transcribed, the MET protein is more stable and less prone to degradation, thereby increasing MET signaling [MET exon 14 skipping mutations are found in about 3% of patients with NSCLC [ignaling . In a trth NSCLC . MET amplification results in an increase in the number of copies of MET, either through focal amplification or chromosome 7 polysomy. While focal MET amplification has been associated with oncogenicity, amplification through chromosome 7 polysomy is typically not. Focal MET amplification is found in 1–6% of treatment-naïve NSCLC [MET amplification is seen more frequently after first-line treatment with osimertinib than in a treatment-naïve population and is the most common mechanism of resistance to osimertinib identified [ve NSCLC , and hasve NSCLC . MET ampMET testing at either time of diagnosis or at time of progression on targeted therapy. MET alterations can be tested for using a variety of methods, including both tumor tissue testing and liquid biopsy testing. MET amplification is traditionally diagnosed through fluorescence-in-situ-hybridization (FISH) of tissue obtained by biopsy. MET amplification by FISH is defined using two main strategies. The first determines gene copy number (GCN), with multiple cutoffs used, commonly a GCN of five or more, but also six or fifteen have been used as cutoffs. An alternative method is to control for chromosome 7 by using a ratio of MET per cell to chromosome 7 centromere (MET/CEP7). With this method, a MET to CEP7 ratio of greater than 2 is the typical definition of MET amplification [Currently, there is not a uniform practice for how to perform fication .MET amplification. As with FISH, there is not a consensus of copy number to define amplification. Unlike FISH, NGS does not control for chromosome 7 copy number [MET amplification diagnosed with FISH compared to NGS, so a higher GCN cutoff of at least 10 is often used. With a higher cutoff, concordance with FISH is improved, but low to moderate MET amplification is less likely to be detected. At these levels, FISH has improved detection compared to NGS [NGS can also be used for the detection of y number . There hd to NGS . MET exon 14 skipping mutations, NGS is overall the preferred strategy [MET exon 14 skipping as a single gene testing could also be a reasonable approach [However, for detecting strategy . There istrategy . Qt-PCR approach . MET alterations. Different IHC cutoffs for determining high MET expression have been used in clinical trials and vary in both the minimum percent of tumor cells expressing MET and in level of IHC positivity (2+ vs. 3+). IHC appears to be less sensitive in detecting both exon 14 skipping mutations and MET amplification [MET amplification. IHC has also been studied for diagnosis of fication . Thus, FMET, though interpretation of MET amplification can be difficult using this platform [MET exon 14 skipping mutations, cfDNA was obtained baseline and on treatment. A total of 67% of patients had a molecular response, which had a high concordance with clinical response [The use of cell-free DNA (cfDNA) testing in non-small cell lung cancer has increased dramatically over the past five years. Liquid biopsy can provide either a complementary or an alternative method of genomic profiling in addition to or in place of tissue moleculars. cfDNA NGS can also be used to diagnose alterations of platform . An addiplatform . Cell-frresponse . MET alterations, clinical trials use multiple of these methods to determine what is considered MET-altered NSCLC, and future study could benefit from a standardized approach. However, given the implication of MET in resistance mechanisms, rebiopsy or liquid biopsy for genomic profiling of resistance is warranted in patients who progress after EGFR inhibition and may reveal MET alterations for targeted treatment.Without a consensus in method of detecting ALK or ROS1 rearrangements in NSCLC [MET exon 14 alterations who received crizotinib, the objective response rate (ORR) was 32% (95% CI 21–45%) with a median progression free survival (PFS) of 7.3 months (95% CI 5.4–9.1 months). The most common adverse events seen with crizotinib included edema (51%), vision disorder (45%), diarrhea (39%) and vomiting (29%). Most common grade 3 or greater adverse events were transaminitis (4%) and dyspnea (4%) [TKIs with activity against MET are defined by how they bind MET as well as whether they are selective or non-selective for MET. Type 1 MET TKIs compete with ATP and are divided into Type 1a and Type 1b based on where they bind to MET. Type 1a binds the solvent front residue, which is not specific to MET, and are therefore non-selective MET inhibitors. Type 1b selectively binds MET. Type 2 MET TKIs differ in binding inactive MET and are also non-selective. Non-selective MET inhibitors include both crizotinib and cabozantinib. Crizotinib is a type 1a or non-selective MET TKI in that it inhibits MET in addition to ALK, ROS, and RON. It was initially approved for in NSCLC ,29. In tnea (4%) . EGFR wildtype, but not mutant, patients. In a phase II trial, 42 patients with EGFR wildtype advanced non-squamous NSCLC who had received one or two previous treatments were randomized to receive erlotinib, cabozantinib, or combination erlotinib and cabozantinib. MET alterations were not specifically tested for. PFS was longer with cabozantinib alone  and with combination erlotinib and cabozantinib  than with erlotinib monotherapy . Adverse events with cabozantinib were most commonly fatigue (55%), diarrhea (50%), and nausea (45%). Of grade 3 or greater adverse events, hypertension (25%), fatigue (15%), and oral mucositis (10%) were most common [Cabozantinib is a type II non-selective MET TKI. In addition to MET activity, it also targets VEGFR, RET, TIE2, FLT-3, and KIT. Cabozantinib is currently approved for renal cell carcinoma, medullary thyroid carcinoma, and hepatocellular carcinoma. Studies of cabozantinib in NSCLC are more limited. In advanced NSCLC, cabozantinib has been studied in t common .Type 1b MET inhibitors are selective in their inhibition of MET. This class of drugs has had recent FDA approvals after demonstrating success in multiple recent clinical trials, based on an improvement in both efficacy as well as decreased toxicity given there is less off-target activity. This class includes tepotinib, capmatinib, and savolitinib. MET exon 14 skipping alterations. The phase II VISION trial studied tepotinib in cohorts of both MET amplified and MET exon 14 skipping as a mix of first-, second-, and third-line therapy. MET exon 14 skipping was determined by liquid biopsy or RNA NGS of tissue. In 152 patients treated with tepotinib, the ORR was 46% (95% CI 36–61%) and was similar when stratified by prior therapy, and a median PFS of 8.5 months (95% CI 6.7–11.0) was seen. Grade 3 or greater adverse events occurred in 28% of patients, most commonly peripheral edema (7%), increased lipase (3%) and amylase (2%) [Tepotinib is a selective MET inhibitor that is FDA approved in patients with NSCLC with ase (2%) . MET amplification consisted of 24 patients with amplification determined by liquid biopsy. Median PFS was 4.2 months (95% CI 1.4-NE) in this cohort. The overall ORR was 42% (95% CI 22–63), with a 71% (95% CI 29–96) response rate seen in treatment-naïve patients, 30% (95% CI 7–65) as second-line therapy, and 29% (95% CI 4–71) as third-line therapy. A total of 67% of patients had treatment-related adverse events, most commonly peripheral edema (38%), generalized edema (17%), and constipation (17%). Grade 3 or greater adverse events were experienced by 29% of patients, most commonly peripheral edema (8%) and generalized edema (8%) [The VISION cohort of ema (8%) . MET exon 14 skipping mutations. In the GEOMETRY mono-1 phase II clinical trial, patients with MET dysregulated advanced NSCLC were treated with capmatinib. In those with MET exon 14 skipping mutations, the ORR was 41% (95% CI 29–53) with a median PFS of 5.4 months (95% CI 4.2–7.0). In patients who had not received prior treatment, the ORR was higher at 68% (95% CI 48–84) with a higher median PFS as well at 12.4 months (95% CI 8.2-NE). However, in patients with MET amplification, efficacy was limited to those with high gene copy numbers, with an ORR of 29% (95% CI 19–41) and a median PFS of 4.1 months (95% CI 2.9–4.8) in those with a gene copy number of greater than 10. Peripheral edema (51% of patients) and nausea (45%) were the most common adverse events. Grade 3 or higher adverse events were seen in 67% of patients; most commonly peripheral edema (9%) and dyspnea (7%) [Capmatinib is a selective MET inhibitor that is FDA approved for NSCLC with nea (7%) . MET exon 14 skipping mutations. Savolitinib was studied in a phase II trial in China in advanced or metastatic NSCLC with an exon 14 skipping mutation and that has progressed or had toxicity to a prior treatment. The ORR was 49.2% (95% CI 31.1–55.3) with a PFS of 6.9 months (95% CI 4.6–8.3). All patients had a treatment-related adverse event, most commonly peripheral edema (54%), nausea (46%), and transaminitis (37–39%). Grade 3 or greater treatment-related adverse events were seen in 46% of patients, most commonly transaminitis (10–13%) and peripheral edema (9%) [Savolitinib is a selective MET TKI that is approved in China for NSCLC with ema (9%) .MET expression was performed, defined as IHC with MET expression level of 3+ in at least 90% of tumor cells, which 24 patients met. With this definition of high MET expression, progression free survival with emibetuzumab plus erlotinib was 20.7 months vs. 5.4 months with erlotinib alone . Toxicity was higher in the combination arm, with peripheral edema (11.3% vs. 0%) and mucositis (15.5% vs. 8.6%) occurring more frequently than in those who received erlotinib alone [MET antibody-directed therapy is another area of active development and clinical investigation. One of the first promising signals of efficacy was emibetuzumab, a humanized immunoglobulin G4 monoclonal bivalent MET specific monoclonal antibody. Emibetuzumab has both ligand dependent and independent effects, both blocking HGF from binding MET and leading to MET being internalized and degraded. In a phase II trial, patients with stage IV EGFR mutated NSCLC were randomized after 8 weeks of erlotinib to continuing erlotinib monotherapy or to erlotinib plus emibetuzumab 750 mg infusion every 2 weeks. There was no difference in progression free survival between the overall groups (9.3 months with combination therapy and 9.5 months with erlotinib monotherapy). A post-hoc analysis of those with high ib alone . MET. Onartuzumab blocks interaction with HGF by binding to extracellular MET. Phase II and III trials have studied onartuzumab in combination with erlotinib and chemotherapy without demonstrating a benefit in PFS or overall survival (OS) [MET Lung trial studied onartuzumab with erlotinib or placebo infusion plus erlotinib. 499 patients with locally advanced or metastatic NSCLC with MET positive status defined as IHC 2+ or greater in at least 50% of cells who had progressed after platinum-based chemotherapy were enrolled. Shorter OS was seen in in the onartuzumab arm at 6.8 months vs. 9.1 months with placebo . Peripheral edema (21.8% vs. 7.8%) and hypoalbuminemia (17.3% vs. 3.7%) were more common in the onartuzumab arm than erlotinib monotherapy [Onartuzumab is a recombinant, humanized monoclonal antibody against val (OS) ,36,37. Totherapy . Grade 4MET amplification or exon 14 skipping mutation received Teliso-V monotherapy. 40 c-MET+ patients were enrolled, and the ORR was 23% (95% CI 10.8–38.5) with median PFS of 5.2 months. A total of 65% of patients had grade 3 or greater adverse events, most commonly anemia (10%), fatigue (8%), and peripheral neuropathy (6%) [Teliso-V is an antibody-drug conjugate of the telisotuzumab humanized monoclonal antibody which targets c-MET conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE). In a phase I/Ib study, patients with NSCLC and a c-MET H-score of at least 150 or local lab reported thy (6%) . AnotherEGFR-mutated advanced NSCLC and the prevalence of MET dysregulation in resistance to third generation EGFR inhibitors, inhibition of EGFR and MET in combination has been a preferred strategy in clinical investigation in patients previously treated and progressed after initial EGFR inhibitor therapy. With uncertainty in how to treat patients with MET-amplification-mediated resistance to EGFR-TKI, real-world data does support the approach of combination EGFR and MET inhibition. 70 patients received either EGFR-TKI and crizotinib (n = 38), crizotinib monotherapy (n = 10), or chemotherapy (n = 22). PFS was longer in combination inhibition than with crizotinib monotherapy or chemotherapy  [Considering the demonstrated benefit of EGFR inhibition in ctively) . More reWith multiple EGFR and MET inhibitors available, trials have studied different combinations of these inhibitors to identify a dual-inhibition strategy with significant anti-tumor activity as well as an acceptable risk profile. Results of trials utilizing and EGFR TKI and a MET TKI are summarized in EGFR positive and MET over-expressed advanced NSCLC, EGFR TKI monotherapy (n = 48), EGFR TKI plus crizotinib (n = 9), EGFR TKI plus chemotherapy (n = 12), and chemotherapy alone (n = 35) were compared. MET overexpression was defined by IHC with above-median H-score and 2+ or 3+ staining in 50% or greater of tumor cells. Notably, EGFR TKIs varied and included geftinib, erlotinib, afatinib, and osimertinib. This study showed that those treated with an EGFR-TKI (monotherapy and combination with crizotinib) had a longer PFS than chemotherapy . EGFR TKI monotherapy or with crizotinib had comparable PFS . Grade 3 or greater rashes were more common in patients who received EGFR-TKI plus crizotinib (0% vs. 33.3%) [In a study of 104 treatment-naïve patients with de novo . 33.3%) .EGFR-positive, MET-amplified NSCLC who had progressed on prior EGFR TKI treatment received capmatinib in combination with gefitinib. MET amplification was defined as GCN of at least 5 and/or a MET/centromere ratio of 2 or greater or MET overexpression with at least 50% of tumor cells with moderate or strong IHC staining. The ORR across the phase Ib/II study was 27%. In patients with high MET amplification defined as gene copy number of at least 6 , a higher ORR of 47% was seen. The most common adverse events were nausea (28%), peripheral edema (22%), decreased appetite (21%), and rash (20%). Grade 3 or greater adverse events were seen in 33% of patients, most commonly increased amylase or lipase (both in 6%) [In a phase 1b/II trial, patients with h in 6%) . MET-amplified, EGFR-mutated NSCLC who had progressed on EGFR TKIs. Osimertinib was studied in combination with multiple other targeted therapies: selumetinib (MEK1/2 inhibitor), durvalumab , and savolitinib. MET amplification was defined as FISH with GCN of 5 of greater or MET-CEP7 ratio 2 or greater, IHC with 3+ expression in 50% of cells, or NGS with 5 or greater copies in 20% of tumor cells. Cohorts were stratified based on exposure to prior third generation EGFR TKI, and in those without prior third generation TKI, whether EGFR T790M was present [TATTON was a phase 1b study of locally advanced or metastatic  present .In patients previously treated with a third generation EGFR TKI, the ORR of savolitinib plus osimertinib was 33% (95% CI 22–46). However, in those who had not been previously treated with a third generation EGFR TKI, ORR was even higher, ranging from 62–67% and regardless of T790M status . Nausea EGFR mutant NSCLC previously treated with first-line osimertinib with MET alterations in the ORCHARD study. MET amplification and exon 14 skipping mutations were included and identified by NGS of tumor biopsy. In 20 patients, an ORR of 41% was seen. A total of 30% had a grade 3 or greater adverse event, most commonly pneumonia and decreased neutrophil count (10% each) [The combination of osimertinib and savolitinib was also studied in 0% each) . MET overexpression or amplification [MET-amplified or overexpressed and EGFR-positive locally advanced or metastatic NSCLC [The phase II SAVANNAH trial is currently investigating savolitinib plus osimertinib as second-line therapy in patients with acquired resistance to osimertinib fication . The phaic NSCLC .EGFR-mutant MET-amplified advanced NSCLC in China after progression following prior EGFR TKI therapy. MET amplification was determined by FISH with a GCN or 5 or greater or MET-CEP7 of 2:1 or greater. ORR overall was 31%, with higher ORR seen in EGFR T790M negative (52%) and lower seen in EGFR T790M positive (9%). Most common adverse events were vomiting (46%), nausea (40%), and increased aspartate aminotransferase (39%). Most common grade 3 or greater adverse events included transaminitis (AST and ALT 7% each), and increased gamma-glutamyltransferase (5%) [In a phase 1b trial, combination savolitinib and gefitinib were studied in patients with vomiting %, nauseaMET-positive NSCLC. This included a cohort of patients with EGFR mutations designated Cohort A with 12 patients. ORR in this cohort was 50%. Most common adverse events were rash (63%), fatigue (51%), and nausea (45.7%). Grade 3 or greater adverse events were seen in 34% of patients, most commonly decreased lymphocytes (9%), limb edema (6%), anorexia (6%), and increased lipase (6%) [In a phase I/II dose escalation trial, combination capmatinib and erlotinib were studied in ase (6%) .EGFR-mutated NSCLC that were T790M negative and MET overexpression (IHC 2+ or 3+) or MET amplified by FISH (GCN 5 or greater or MET/CEP 2 or greater). In the phase 2 trial, patients were randomly assigned to tepotinib plus gefitinib at the phase 1b determined dose of 500 mg or standard platinum doublet chemotherapy. Final analyses of phase 2 with 55 patients are now published, and in the group at large, median PFS was similar at 4.9 months with tepotinib and gefitinib vs. 4.4 months with chemotherapy. In the 19 patients with MET amplification, tepotinib plus geftinib had longer PFS  and OS  than chemotherapy. ORR was 66.7% with combination TKI therapy compared to 42.9% with chemotherapy [The INSIGHT-1 phase 1b/2 trial studied tepotinib plus gefitinib in patients with otherapy . Rates ootherapy . EGFR-mutant NSCLC with acquired resistance to first-line osimertinib and with MET amplification determined by FISH with GCN of 5 or greater or MET/CEP7 of 2 or greater [INSIGHT 2 is an ongoing phase II trial of tepotinib plus osimertinib in advanced  greater . Initial greater .Results of combination EGFR- and MET-inhibition-utilizing antibodies and antibody drug conjugates are summarized in MET expression were randomized 3:1 to either emibetuzumab with erlotinib or emibetuzumab monotherapy. Increased MET expression was defined IHC with as at least 10% of cells expressing MET at 2+. ORRs were low: 3% for emibetuzumab plus erlotinib (95% CI 0.4–10.5) and 4.3% for emibetuzumab monotherapy (95% CI 0.1–21.9). With combination therapy, fatigue (29%), diarrhea (25%), and nausea (23%) were the most common adverse events overall. Grade 3 or greater adverse events were seen in 24.1% of patients on combination therapy, most commonly dermatitis acneiform (6%) and hypoalbuminemia (3.6%) [In a randomized phase II trial, patients with stage IV NSCLC with acquired resistance to erlotinib with increased a (3.6%) .EGFR positive NSCLC who had progressed on a prior EGFR TKI. Patients were c-MET positive determined by histology H score of at least 150. Median PFS was 5.9 months (95% CI 2.8 to not reached). ORR was 30.6% (95% CI 16.3–48.1), and in those who were c-MET high defined as H score 225 or greater, ORR was 52%. The most common adverse events were neuropathies (57%) and dermatitis acneiform (38%), with grade 3 treatment-related AEs in 31% of patients, most frequently hypophosphatemia (7%) and peripheral sensory neuropathy (7%) [Teliso-V was studied in a phase 1b trial in combination with erlotinib in 42 patients with opathies % and derEGFR and MET status [EGFR mutations. Results have been presented at ASCO and ESMO. In patients who had progressed on osimertinib, an ORR of 36% was seen in those treated with combination amivantamab and lazertinib, with median PFS of 4.9 months. This is compared to ORR 19% and median PFS 4.2 months with amivantamab monotherapy [EGFR mutant advanced NSCLC who had progressed after osimertinib and platinum-based chemotherapy. In this population, an ORR of 33% was seen [Amivantamab is a bispecific antibody for both EGFR and MET. Amivantamab was studied in patients with advanced NSCLC in cohorts based on T status . In the otherapy ,60. CHRYwas seen . EGFR exon 20 insertion mutations were also enrolled. In patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who had progressed on or after platinum-based chemotherapy, an ORR of 40% (95% CI 29–51) was seen. Amivantamab received accelerated FDA approval in this setting based on these results [In the CHRYSALIS trial, a cohort of patients with  results .EGFR+ NSCLC are ongoing. In safety analyses of amivantamab, the most common adverse events were rash (86%), infusion-related reactions (66%), and paronychia (45%). Grade 3 or greater adverse events occurred in 35%, most commonly hypokalemia (5%), rash, pulmonary embolism, diarrhea, and neutropenia  . The MARMET amplification as a resistance mechanism to EGFR TKIs. Establishing a universal definition of MET amplification or overexpression with a focus on FISH and NGS as more sensitive diagnostic methods will be important in standardizing reporting establishing clinical trial eligibility. While tissue and cfDNA NGS have had significant uptake in recent years, it is unclear to what degree MET FISH is being performed for NSCLC off protocol and as standard of care. The optimal method for targeting MET amplification or overexpression has yet to be determined. As detailed above, MET is being targeted by TKIs, antibodies, and antibody drug conjugates. It is unclear if one particular drug or modality will have a clear advantage as far as efficacy or toxicity, or if these decisions will need to be made on an individual patient basis. Additionally, as clinical trials are now being designed to move MET-directed therapy to frontline treatment for EGFR-mutated NSCLC patients, it is yet unknown if this will yield benefit for all patients, or if additional biomarker studies are needed to understand exactly which patients benefit from a combination approach.There are several areas of clinical study that can help to move the field forward for MET dysregulation, particularly MET amplification, has been identified as a common mechanism of resistance. However, identifying a standardized definition of MET amplification for trial eligibility is needed. Identifying driver mutations and targeted therapies has developed a new standard of care for many patients with NSCLC. By identifying the genetic drivers of EGFR inhibitor resistance in a similar way of identifying initial driver mutations, the same principle of targeting these genetic drivers could be a strategy to delay progression and potentially delay the need for chemotherapy. In studies of genetic alterations after progression on osimertinib, EGFR positive NSCLC. Multiple drugs that inhibit MET have been studied in advanced NSCLC, including tyrosine kinase inhibitors, antibodies, and antibody-drug conjugates. Combining EGFR inhibition and MET-directed therapy has been a promising area of clinical study. In early clinical trials, both combination TKI therapy, and combination TKI and antibody, antibody-drug-conjuate, and bi-specific EGFR-MET antibody have shown anti-tumor activity. Large-scale clinical trials of combination EGFR-MET inhibition are needed to understand the clinical benefit of this treatment strategy, as well as to consider this strategy as potential first-line therapy in advanced


Antibiotic resistance has been a challenge to the medical fraternity and has had a massive impact on disease management. The overuse of antibiotics and careless prescription by doctors have been one of the primary reasons for the development of antibiotic resistance among the masses. This article draws attention to the significant reasons causing antibiotic resistance, such as overuse, antibiotic resistance genes, and extensive use of antibiotics in agriculture. It also brings forward the challenges posed by antibiotic resistance in the management of various diseases like tuberculosis, COVID-19, and vancomycin-resistant enterococci infections. The article includes a case study that depicts the threat posed by antibiotic resistance in tuberculosis treatment. This article also shows the effects of antibiotic resistance on COVID-19 patient care and treatment.It further includes methods that can be implemented on international levels as well as individual ground levels to curb antibiotic resistance. One of the methods has a recent finding in which proteins produced in the body are being modified and used in treatments to reduce the use of antibiotics, which ultimately serves the goal of curbing antibiotic resistance by reducing overuse. Antibiotics are one of the wonder discoveries of the twentieth century . AntibioMethodologyTo search the Central database and MEDLINE, we used Cochrane Library and PubMed. For each database, the following search approach was created: ((Antibiotic resistance) AND ("Tuberculosis drugs") AND ("Antibiotic Resistance Genes")) :  AND  that destroyed the drug [Many human gene transfer (HGT) methods free genes from typical vertical inheritance. By concentrating antibiotic-resistant genes (ARGs) in a single cell, HGT promotes the emergence of incurable "superbugs." One of the most known examples is the drug . A genetInappropriate Use and Prescription of AntibioticsS. aureus has increasingly developed a higher level of drug resistance as a result of bacterial evolution and antibiotic misuse. Methicillin-resistant Staphylococcus aureus (MRSA) infection rates have increased globally, and its clinical anti-infective therapy has been increasingly challenging. Research has shown that the resistance mechanisms of S. aureus are exceedingly intricate, particularly for MRSA, which is resistant to a wide range of antibiotics [According to estimates, 30% of the annual millions of prescriptions supplied are unnecessary. Over the past few decades, ibiotics . Investiibiotics . Since tibiotics . The intThe Extensive Use of Antibiotics in AgriculturePrescriptions for antibiotics are part of the therapeutic regimens used to eradicate infections in humans. Antibiotic use is not only restricted to clinical settings ,13. The Consequences of antibiotic resistanceVarious diseases and their hindered management because of antibiotic resistance are discussed below.Antibiotic Resistance in TuberculosisMycobacterium tuberculosis populations that may momentarily withstand antibiotic pressure in the absence of changes that give drug resistance can limit effective tuberculosis treatment [Mycobacterium tuberculosis resistant to rifampicin was found [reatment . In a streatment . Drug rereatment . In severeatment . A case reatment . On assaas found . He did as found .Antibiotic Resistance in COVID-19More than 29,400 people died in the first year of the epidemic from illnesses that are frequently linked to healthcare . The COVOther Life-Threatening Bacterial Infections That Have Antibiotic ResistanceH. pylori has alarmingly increased everywhere. This has significantly impacted how well this bacterial ailment is treated [Pseudomonas aeruginosa is the main cause of illness and mortality in cystic fibrosis sufferers and other immunocompromised individuals. Its remarkable capacity to resist antibiotics has made its eradication extremely difficult [E. coli antibiotic resistance [The female vaginal system and the human digestive tract are frequently colonized by enterococci bacteria. Hospitals and healthcare facilities are major hubs for vancomycin-resistant enterococci infections. Patients with underlying health conditions are more vulnerable to infection by these bacteria. Antibiotic resistance in  treated . An aggrifficult . Since Eifficult . Becauseifficult . Physicisistance . Common sistance . Gram-nesistance . For exasistance . There wsistance . The WHOsistance .Methods to Curb Antibiotic ResistanceThe goal of One Health is to achieve the highest possible level of health for everyone, including domesticated animals, wildlife, plants, and the environment . This enAntibiotics have given the health sciences extraordinary benefits, and the rapid increase in antibiotic resistance is threatening it. This is a global crisis that reflects the worldwide overuse of antibiotics, and pharmaceutical companies are lacking to develop new antibiotics to address the challenge. Antibiotic resistance is putting the achievements of modern medicine at risk. Antibiotic-resistant infections place a substantial economic burden on the healthcare system worldwide. The world is in urgent need of coordinated efforts to curb this crisis; the international health governing bodies, along with the personal level in the community, the society, can overcome antibiotic resistance.


The research focuses on effectively utilizing industrial by-products, namely fly ash (FA) and ground granulated blast furnace slag (GGBS), to develop sustainable construction materials that can help reduce carbon emissions in the construction industry. Geopolymer mix design using these by-products is identified as a potential solution. The study investigates the impact of different water to binder ratios (W/B) ranging from 0.4 to 0.6 on the residual properties, including compressive strength (CS), of geopolymer concrete (GPC), in accordance with Indian Standard for Alkali activated concrete. Lower W/B ratios were found to result in a more compact and less porous microstructure in the GPC. Additionally, the research explores the post-fire performance of GPC with varying grades  and different W/B ratios, following the ISO 834 standard fire curve. It was observed that concrete samples exposed to elevated temperatures displayed a more porous microstructure. The mass loss of GPC with 0.4 W/B was found to be 2.3–5.9% and for 0.6 W/B ratio, the loss was found to be 3–6.5%, after exposing to 30-, 60-, 90-, and 120-min of heating. In the case of strength loss, for 0.4 W/B ratio, the loss was 36.81–77.09%, and for 0.6 W/B ratio the loss was 38.3–100%, after exposing to 30-, 60-, 90-, and 120-min of heating. Overall, the findings suggest that optimizing the W/B ratio in geopolymer concrete can enhance its compressive strength, as well as residual properties, and contribute to its suitability as a sustainable construction material. However, the response to elevated temperatures should also be considered to ensure its performance in fire scenarios. Due to its adaptability, durability, and performance, concrete is the most frequently employed construction materials worldwide. Nonetheless, the production of cement, which serves as concrete’s principal component, and it is responsible for a notable proportion of carbon emissions. The cement industry is a primary cause for 7% of global carbon dioxide emissions . AdditioAnother drawback of cement concrete is its poor resistance to chemical attack. When exposed to acidic or alkaline environments, the concrete can deteriorate, leading to a reduction in strength and durability . This caGeopolymers are an innovative class of materials that serve as an alternative to traditional cement-based materials like concrete . They ar2 Emissions [Geopolymers require a curing period to develop their strength and durability. This curing process can occur at room temperature or under controlled heat conditions . Advantamissions : Geopolymissions . While gmissions . AdditioThe production process of GPC involves the synthesis of a geopolymer binder that acts as a replacement for cement. The geopolymer binder is formed by activating the industrial by-products with an alkaline solution, typically a mixture of sodium hydroxide and sodium silicate . The synThe process of making GPC involves several steps, including mix design optimization, mixing of ingredients, casting, and curing . Mix desHowever, despite of its many advantages, GPC also has several drawbacks that need to be addressed. One of the major drawbacks is the relatively higher cost of production compared to traditional cement concrete . The cosFurthermore, the long-term durability of GPC is still not fully understood, particularly in harsh environments such as seawater exposure and freeze-thaw cycles. Seawater exposure: GPC generally displays favorable characteristics when exposed to seawater due to its resistance to chemical attack, reduced permeability, and potential resistance to alkali-silica reaction. However, while it holds promise for marine applications, ongoing research and testing are necessary to refine mix designs to understand its behavior over time when subjected to the unique challenges posed by seawater environments . Freeze-Most of the past studies deal with the concrete subjecting to random temperature exposure. This means that in previous studies, researchers subjected concrete samples to varying and unspecified temperature conditions, possibly simulating fire or heat exposure, but without adhering to a specific standardized guideline. The temperature conditions might have been randomly chosen or not based on a recognized industry standard. Whereas, the present study focuses on the use of ISO 834 standard guidelines for heating the concrete samples. In contrast to the past studies, the current study is designed to follow the ISO 834 standard guidelines. ISO 834 is an internationally recognized standard that provides guidelines for simulating fire exposure on building elements, including concrete, in a controlled and consistent manner. This standard specifies a heating curve that represents the time-temperature relationship of a real building fire.In this case, the concrete specimens were exposed to real-time fire exposure as set by ISO 834. The temperature conditions applied to the concrete specimens in the study closely mimic the heat that would be experienced by real building elements during a fire, following a specific time-temperature profile.Utilization of Indian Standard for Alkali activated concrete: This research paper marks a pioneering effort by utilizing the guidelines specified in this Standard; it is the comprehensive code providing guidelines for development of the alkali-activated concrete.Optimized Geopolymer Formulation: The study focuses on optimizing the geopolymer concrete mix design as per Indian Standard, considering locally available materials and environmental influencing factors. This contributes to the practicality and sustainability of geopolymer concrete application in various regions.Thermal Resistance Assessment: Geopolymer concrete’s performance under extreme temperature conditions is a critical factor for its widespread application. The paper rigorously evaluates the concrete’s behavior when subjected to elevated temperatures following the ISO 834 standard guidelines. This evaluation provides valuable insights into its fire resistance and suitability for applications in fire-prone areas.Enhanced Infrastructure Resilience: The research outcomes have the potential to significantly enhance the resilience of critical infrastructure, such as bridges, tunnels, and high-rise buildings, by offering a sustainable and fire-resistant alternative to traditional concrete.2/kg and 510 m2/kg.Low calcium Fly ash (FA) obtained from coal fired thermal power plant, Mettur, India. Ground granulated blast furnace slag (GGBS) obtained from JSW steel plant, Salem, India. FA and GGBS was employed as the binder material for the production of concrete. 3 and 1821 kg/m3.Due to scarcity of river sand, the manufactured sand (M-sand) was employed as the fine aggregate in the construction industry. The crushed granite stones were employed as the coarse aggregate for the production of concrete. The M-sand of size 4.75 mm and below were employed, whereas coarse aggregate of size 12.5 and 10 mm, in the ratio of 60:40 was employed for the concrete production. Particle size distribution of fine and coarse aggregate was depicted in 2SiO3)  conforming to IS 381 [2SiO3 employed in the present investigation is 1.29 and 1.55. Sodium hydroxide (NaOH) conforming to IS 252 , and Sodo IS 381  were empInitially, the binder and the filler materials are mixed in dry state, then followed by the addition of activator solution. The mixing was continued until the uniform consistency was achieved. After achieving the uniform consistency, the freshly prepared mix was checked to assess its physical properties. After which the mix was poured into the mold of required size to assess its mechanical properties. The mix cast was allowed to set for a period of 24 h, beyond which the concrete samples were demolded and allowed in ambient or in oven conditions until the corresponding day of testing.The choice of curing method for GPC largely depends on the raw materials and mix composition used. Various methods, such as thermal curing, water curing, and curing with compounds, can be employed to achieve the desired concrete properties. However, it is important to note that the optimal curing method may vary depending on the specific system being used. For instance, thermal curing may be more appropriate for low-calcium systems, while air or water curing may be more suitable for high-calcium systems. Additionally, it is crucial to take measures to prevent the leaching of alkali activators during the curing process.As per IS 516 , CS of tI denote the absorption, mt is the change in mass in grams, a is the area of the specimen, and d is the density of water.The sorptivity of a GPC mix, which refers to the process of water molecules moving upwards from the base to the top of the concrete specimens through capillary action within a specific time, was determined according to the ASTM C 1585  standardThe purpose of the experiment was to evaluate the residual strength of the GPC that had been developed. To achieve this, the concrete samples were subjected to varying levels of heat using an electric furnace with a maximum temperature capacity of 1200 °C. The heating procedure adhered to the ISO 834  standardAfter heating the concrete specimens in the computerized electric furnace at the target temperature, the specimens were cooled under room temperature. After which the thermal cracks developed on the surface of the concrete specimen were measured using “Elcometer”. Elcometer provides a low-cost microscope for determining the width of a crack in concrete or other building materials.The Scanning Electron Microscope (SEM) was performed using a high range of Phenom ProX desktop SEM. The resolution of the SEM was not less than 8 nm with an increased depth field and an accelerating voltage of 15 kV. The samples are procured from 28-d aged CS tested specimens to examine the polymerization rate and sufficiency of geopolymer gel in the matrix.The W/B ratio is a critical factor that can affect the CS of GPC . In geneBased on the experimental investigation, it is found that an increase in W/B ratio decreases the CS of the concrete. The mix with 0.6 W/B ratio, possess the lowest strength of 20.6 MPa, and the mix with low W/B ratio of 0.4 attained a CS of 42.5 MPa in accordance with IS 516 . The strIt is worth noting that the CS of the geopolymer mix is highly influenced by various factors. Hence, to achieve the desired strength and performance, it is crucial to carefully select the mix design and optimize the various parameters involved in the geopolymer mix.Further, the CS of the GPC was influenced by several factors, including:Chemical composition : The cheCuring conditions : The curAggregate type and size : The typW/B ratio : The W/BAge : The CS Testing methods : The CS The sorptivity test is a common method for evaluating the permeability and durability of concrete . It measThe sorptivity of GPC can be further reduced by optimizing the curing conditions, such as temperature and humidity, to enhance the development of the geopolymer matrix . The sorIn addition, lower W/B ratio GPC mixes tend to have a denser microstructure due to the reduction in porosity, which makes it more difficult for water to penetrate into the concrete matrix. However, the higher number of voids or pores present in lower W/B ratio mixes can offset this effect and lead to a higher rate of absorption. It is worth noting that the rate of absorption of GPC is also influenced by other factors such as the type and amount of activators, curing conditions, and the nature of the aggregate used . TherefoThe mass loss (ML) of all the concrete specimens was evaluated after they were exposed to varying temperatures, and the results are shown in These results indicate that as the grade of the concrete increases (from M10 to M40), the amount of moisture loss also tends to increase. Moreover, the longer duration the specimens are exposed to elevated temperatures, the greater the mass loss becomes. These findings suggest that the M10 mix exhibits relatively lower moisture loss compared to the higher-grade concretes  under the same temperature exposure conditions. The experimental study revealed that concrete with a lower water-to-binder (W/B) ratio exhibited superior performance compared to concrete with a higher W/B ratio when subjected to elevated temperatures. This observation can be attributed to the generation of high internal pressure within the concrete having a high W/B ratio during temperature exposure. The high W/B ratio in concrete means that there is a greater amount of water present relative to the amount of cementitious binder. When this type of concrete is exposed to elevated temperatures, the water within it undergoes vaporization and turns into steam. The conversion of water into steam generates significant internal pressure within the concrete mass.The accumulation of high internal pressure within the concrete with a high W/B ratio leads to several detrimental effects . One majThe examination of crack intensity at the concrete surface is a widely utilized method to assess the deterioration of concrete after exposure to elevated temperatures . This prBy utilizing the elcometer to measure crack widths up to 1.8 mm, researchers can gather precise data, enabling quantitative analysis of crack patterns and intensities. This quantitative assessment offers insights into the damage mechanisms, helps to identify critical areas of deterioration, and informs decisions regarding potential repair strategies or modifications to enhance the concrete’s resistance to thermal stresses. The observed cracks in the concrete specimens were a direct consequence of the thermal expansion and contraction experienced during the heating and cooling cycles. As the temperature increased, the concrete expanded, and when cooled, it contracted. These thermal movements generated internal stresses that exceeded the tensile strength of the concrete, causing to the development of crack. The increased cracking intensity witnessed at the higher temperature and longer exposure duration highlights the vulnerability of concrete to thermal stresses . It undeThe experimental investigation focused on evaluating the residual strength of GPC samples when exposed to varying temperatures. The experimental investigation specifically analyzed the impact of temperature exposure on the CS of GPC, with a focus on the M40 and M10 concrete grades. The results, as shown in the study, provide valuable insights into the extent of strength loss experienced by these concrete grades under different exposure durations. For the M40 grade concrete, it was observed that after 30 min of temperature exposure, there was a substantial decrease in CS of about 37%. However, the strength loss significantly escalated to 77% after an extended exposure duration of 120 min. These findings demonstrate a substantial and progressive weakening of the concrete’s CS, as the temperature exposure duration increased. Similarly, the M10 grade concrete also exhibited a notable decrease in CS. After 30 min of temperature exposure, the strength loss was measured at 38%. However, the situation worsened when subjected to 120 min of exposure, resulting in a complete loss of CS (100%).These findings highlight the significant negative impact of temperature exposure on the CS of GPC. The results indicate that both the M40 and M10 concrete grades experienced substantial strength reductions, which can be attributed to various factors such as thermal expansion, chemical reactions, and the breakdown of the material’s internal structure. Through the conducted trials and experiments, it was observed that concrete with a lower water-to-binder (W/B) ratio exhibited better performance compared to concrete with a higher W/B ratio. The W/B ratio is a crucial parameter in concrete mix design, representing the ratio of water content to the binder materials (such as cement) used in the mixture. A lower W/B ratio signifies a lower amount of water relative to the amount of binder, resulting in a denser and more compact concrete matrix. The findings from the trials indicated that concrete with a lower W/B ratio demonstrated improved performance in several aspects. One of the key advantages was enhanced strength and durability. The lower water content resulted in a higher concentration of binder materials, promoting better interfacial bonding and overall strength of the concrete . AdditioFurthermore, concrete with a lower W/B ratio exhibited improved resistance to various types of deterioration mechanisms, including cracking, shrinkage, and chemical attack. The reduced water content helped to mitigate the potential for excessive shrinkage and cracking, as well as limiting the availability of water for chemical reactions that could degrade the concrete. In contrast, concrete with a higher W/B ratio demonstrated comparatively inferior performance. The increased water content in these mixtures resulted in a higher porosity and weaker interfacial bond strength . This poThese findings highlight the vulnerability of GPC to thermal stresses. When exposed to high temperatures, GPC undergoes various physical and chemical changes that negatively impact its structural integrity and strength . The theScanning Electron Microscopy (SEM) can be used to investigate the microstructure of GPC with varying water-to-binder (W/B) ratios. SEM images can provide detailed information on the morphology, and distribution of the phases present in the concrete matrix. When the W/B ratio is decreased in GPC, the microstructure becomes more compact and less porous. This is due to the formation of a denser geopolymer matrix, which reduces the amount of water that can penetrate into the concrete. SEM images of GPC with lower W/B ratios typically show a smoother and more homogenous surface, with fewer voids and pores compared to concrete mixes with higher W/B ratios as shown in In Upon subjecting the concrete specimens to temperatures of 925 °C and 1029 °C, it was observed that all concrete grades exhibited a similar behavior. This implies that the temperature-induced changes in the concrete were consistent across different grades of concrete. The cracks became more prominent and extensive, indicating a further degradation of the material. Additionally, the concrete exhibited an increased porosity, implying a higher number of interconnected voids or pores within its structure. This increased porosity further compromised the integrity and strength of the concrete. A number of researchers have done similar experimental studies to the work presented herein and the most relevant of these are summarized in The comparison between the performance of binary blended mix is based on a specific mix proportion of materials used for blending, and the results may vary for other combinations.The decline in CS of concrete after temperature exposure is found for all samples tested, but there may be variations due to factors such as mix composition, curing conditions, and testing methods.The results are based on a limited proportion of samples, and the influence of various parameters on the performance of concrete needs further investigation.Conducting more extensive experiments with a larger number of samples to establish a more reliable database to improve the statistical significance of the results through software simulation and modelling.Investigation on the influence of various parameters, such as precursor type, alkaline activator, activator concentration, reinforcement ratio, intensity and duration of heating, on the performance of concrete.Exploring the potential usage of other Supplementary cementitious materials, such as rice husk ash, bagasse ash and silica fume, into the mix to study their effect on the strength and durability of concrete.Investigation on the long-term behavior of concrete under different environmental conditions, such as freeze-thaw cycles and chloride ingress.Conducting a comparative life cycle assessment (LCA) of concrete with other sustainable construction materials to gain a better understanding of their environmental impact to identify potential areas for improvement.Investigating the potential of using recycled materials in the production of concrete to enhance their sustainability credentials.In this study, a straightforward and effective mix design method is proposed for the development of geopolymer concrete (GPC) using fly ash and ground granulated blast furnace slag (GGBS) as key components. Unlike traditional concrete mix design, which focuses on factors like fine and coarse aggregate quantities, alkaline activator solution, and binder proportions, the proposed approach incorporates the influence of specific gravity of raw materials in the mix design.By adopting this innovative methodology, consistent outcomes are attainable despite variations in the physical attributes of raw materials. Notably, the research reveals that the fundamental principle of strength relative to W/B ratio, as outlined in the Indian standard, is equally relevant to GPC production.Furthermore, proposed study establishes that GPC can achieve compressive strengths (CS) ranging from 10 MPa to 40 MPa after 28 days, even under ambient temperature conditions. Importantly, the results underscore that GPC exhibits superior CS when compared to conventional concrete with identical liquid content.In terms of durability, concrete specimens featuring a W/B ratio of 0.6 exhibit mass losses within the range of 3% to 6.5%. In contrast, specimens with a lower W/B ratio of 0.4 experience slightly lower mass losses, ranging from 2.3% to 5.9%.Analyzing strength degradation, it becomes evident that concrete with a W/B ratio of 0.4 demonstrates a reduction in strength from 36.81% to 77.09%. Conversely, concrete formulated with a W/B ratio of 0.6 displays a somewhat higher strength loss, ranging from 38.30% to 100%.


Antibiotic overuse in children is a significant public health concern, as it can lead to the emergence and spread of antibiotic-resistant bacteria. Although respiratory infections account for most antibiotic prescriptions in children, many of these infections are viral and do not require antibiotics. In this study, we aimed to investigate the use of antibiotics in children with respiratory infections in a primary care setting and to explore the possible role of fever on antibiotic prescription.We conducted a prospective observational study that evaluated preschool children aged 0–5 years who were assessed by their primary care pediatricians for respiratory infectious diseases between October 2019 and March 2021. The study involved 69 public primary care pediatricians and a total of 678 pediatric episodes for respiratory infections.Amoxicillin/clavulanate was the most frequently prescribed drug. Bronchitis accounted for most of inappropriate antibiotic prescriptions (73%). Furthermore, the presence of fever was associated with a ~ 300% increase in the likelihood of prescribing antibiotics for respiratory infections that do not typically require antibiotics.Our findings emphasize the need for adherence to international guidelines and recommendations in the primary care of children to reduce unnecessary antibiotic use and prevent the development of antibiotic resistance. This study also underscores the potential relevance of new studies to evaluate antibiotic prescription attitudes in other clinical settings and geographical areas. Respiratory infections are one of the most common diseases affecting children, and primary-care pediatricians typically manage the majority of cases in outpatient settings . The mosFever is a well-established sign of illness, yet it can trigger fear and anxiety in both parents and healthcare providers , 14. SucThis prospective observational study was performed between October 2019 and March 2021. A total of 69 primary care pediatricians, members of Italian Primary Care Paediatrics Society (SICuPP) in Lombardy Region , were involved. The description of their involvement has been recently reported in detail elsewhere . EligiblFor the descriptive statistics, data are presented as frequency and percentages or median and interquartile range. Missing data were managed with pairwise deletion. Prescriptions of antibiotics for rhinitis, laryngitis, non-streptococcal pharyngitis, bronchitis and bronchiolitis were classified as inappropriate. Chi-Square and Fisher exact tests were used to compare categorical variables. To investigate the association between inappropriate antibiotic prescription and the occurrence of fever, a multiple logistic model was employed. Age and sex were considered for adjustment. A p-value < 0.05 was considered as significant. All analyses were conducted using R-program (2019).The study was conducted in accordance with the Declaration of Helsinki and was approved in September 2019 by the Ethics Committee of the IRCCS Ca’ Granda Ospedale Maggiore Policlinico Foundation, Milan, Italy.Data from 678 pediatric clinical examination conducted for respiratory infections were collected, and 246 antibiotics were prescribed overall (in the 36% of cases). Mean age of the patients was 2.0 ± 1.6 years, 369 of them were male .The primary reason for antibiotic prescriptions was bronchitis, accounting for 38% of cases, followed by otitis media at 30%. Among these diseases, 56% of bronchitis and 73% of otitis were treated with antibiotics Table . Other iThe population was then further analyzed separately considering patients aged 0–2 years  and patients aged 3–5 years (n = 245). No significant difference emerged in the presence of fever or antibiotic prescription between the two populations . As expected, no case of bronchiolitis was diagnosed in the 3–5 years age group. Furthermore, among children with pharyngitis, the percentage of Group A streptococcal pharyngitis was higher in 3–5 years-old children compared to the 0–2 years group . Fever (p = 0.035) and antibiotic prescription (p < 0.01) were significantly more frequent in the 0–2 as compared to 3–5 years age group. Fever occurred in 45% in 0–2 and in 39.2% in 3–5 years age group, whereas antibiotics were prescribed in 36.3% in 0–2 and in 38.8% in 3–5 years age group. No further difference was observed between the two age group patients. Out of 246 antibiotic prescriptions, 185 (75%) were available. Main reason for antibiotic prescription was represented by bronchitis , followed by otitis media . These prescriptions, along with their corresponding percentages of the total, are presented in Table Regarding the total number of antibiotic prescriptions, the majority  were for oral administration of amoxicillin: in 48% of cases it was prescribed alone and in 52% in combination with clavulanic acid. Cephalosporins accounted for 11.4% of all antibiotic prescriptions, while macrolides represented 9% of prescriptions.Among the 678 diagnoses reported, 41.3% of patients presented with fever (n = 280). Out of these patients, up to the 51% of them were prescribed antibiotics, whereas only 26% of non-febrile patients received an antibiotic prescription. In the logistic regression model, the presence of fever was associated with an almost 300% increase in the likelihood of prescribing antibiotics in conditions where it would not generally be recommended (Table Our study aimed to describe the leading causes of antibiotic prescription in a pediatric outpatient population in Italy before and during the COVID-19 pandemic and to evaluate the possible role of fever in the primary-care pediatrician’s choice. This study may represent an overview of the pediatric primary care clinical setting during the first phase of the COVID-19 pandemic in Italy, during which a sudden reduction in pediatric antibiotic prescription has been reported , 19. IndOur results found that bronchitis was the main respiratory reason for antibiotic prescription, followed by otitis media. Indeed, this study points out that healthcare providers should allocate specific attention to the topic of inappropriate prescription of antibiotics for respiratory infections, especially acute bronchitis, which generally only requires supportive treatment . Even ifIn our population fever was a prevalent symptom, and its presence was significantly associated with an almost 300% increase in antibiotic prescription. As fever is a common symptom in childhood and is often linked with viral infections , it cannAmoxicillin/clavulanate has been identified as the most commonly prescribed pediatric antibiotic in primary care settings, consistent with findings from similar studies . DespiteThe main strength of the present study lies in its large sample size, evaluated prospectively immediately before and during most of the pandemic period. However, some limitations should be acknowledged: we did not collect information on the length of the fever before antibiotic prescriptions, the investigation was limited to respiratory diseases and data on the type of antibiotic prescribed were not available in all cases. Furthermore, we did not collect data on the occurrence of chronic diseases. Finally, reasons leading primary care pediatricians to prescribe antibiotics were not investigated in detail.Our study provides insights into the prescription patterns of antibiotics in a pediatric outpatient population and on the possible role of fever in increasing such attitude. The excessive prescription of antibiotics for some respiratory infections, particularly bronchitis, emphasizes the importance of adhering to international guidelines and promoting antibiotic stewardship in the primary care setting. An inappropriate use of antibiotics may affect future treatment options for patients and pose a threat to public health, due to the increasing issue of antibiotic resistance. The overall reduction in the number of antibiotics prescribed during the pandemic provides an opportunity to reflect on prescribing practices and to promote more appropriate antibiotic use.


Background: Shear damage of beams is typically brittle damage that is significantly more detrimental than flexural damage. Purpose: Based on the super-high toughness and good crack control ability of engineered cementitious composites (ECC), the shear performance of concrete–ECC beams was investigated by replacing a portion of the concrete in the tensile zone of reinforced concrete beams with ECC and employing high-strength reinforcing bars to design concrete–ECC beams. The purpose of this investigation is to elucidate and clarify the shear performance of concrete–ECC beams. Methodology/approach: Experimental and FE analyses were conducted on the shear performance of 36 webless reinforced concrete–ECC composite beams with varied concrete strengths, shear-to-span ratios, ECC thicknesses, and interfacial treatments between the layers. Results: The results indicate that the effect of the shear-to-span ratio is greater, the effect of the form of interface treatment is smaller, the effect is weakened after the ECC thickness is greater than 70 mm , the shear resistance is reduced when the hoop rate is greater, and the best shear resistance is obtained when the ECC 70 mm thickness and the hoop rate of 0.29% are used together. Conclusions: This study can serve as a technical reference for enhancing the problems of low durability and inadequate fracture control performance of RC beams in shear and as a guide for structural design research. Reinforced concrete materials are the most widely used construction materials due to their advantages in mechanical properties and engineering costs . HoweverShear resistance design has been a standard topic in structural design, and although the ductility characteristics of concrete can be increased by setting hoop reinforcements, the effect of transmitting the shear force by the hoop and longitudinal reinforcement alone is less than ideal . HippolaRegarding ECC’s unique properties, Li et al.  designedIn recent years, Hou et al.  designedIn contrast, the values calculated with the code method were small, and the differences in the test values were more than half. Deng et al.  investigIn order to study the shear performance of ECC in composite beams and to solve the cracking problem of composite beams, in this paper, based on the existing research on ECC performance, the shear performance of concrete–ECC composite beams is investigated using the design of PVA fibers. The effects of concrete strength, shear-to-span ratio, ECC thickness, and interface treatment on the shear performance of concrete–ECC composite beams are analyzed, and a FE model is established for verification based on experiments. The results can be used as a reference for the design of concrete–ECC composite beams.In this test, 36 specimens of supported beams without web reinforcement were designed, and the geometry and construction of the specimens are shown in (1)“B” means beam without web;(2)“J0” denotes RC (reinforced concrete) control beam;(3)“J1” indicates the test beam with wire mesh at the concrete–ECC interlayer interface;(4)“J2” indicates the test beam with a hemispherical concave surface at the concrete–ECC interlayer interface. (5)“C” indicates concrete; the number after the character “C” indicates the standard compressive strength of concrete;(6)The number after “E” indicates the thickness of the ECC layer.In order to better describe the experimental procedure, The materials used to make the components are mainly ordinary concrete, steel reinforcement, ECC, and fine wire mesh. Among them, the materials for concrete are cement, sand, stone, water, and water reducer; the materials for making ECC are mainly fly ash, cement, silica fume, quartz sand, PVA fiber, water, and water reducer. Some of the tested raw materials are shown in The cement used for the preparation of the concrete and ECC materials in this test was P.O42.5 ordinary silicate cement produced by Yangzhou Green Yang Cement Company , and the main physical properties of this cement are shown in The fly ash used in this paper is the Ⅰ grade ash of Nanjing Thermal Power Plant , whose performance is shown in The quartz sand used for the ECC in this paper comes from the Anhui Fengyang Shengli Sand Factory. The particle size of the quartz sand is in the range of 100~200 mesh. Quartz sand is sand with high purity, high acid and alkali resistance, high refractoriness, and a wide range of uses. This test uses the short-cut 12-type PVA fiber produced by Fujian Baohua Company , and The water used in this test is Yangzhou municipal tap water. The water-reducing agent used is the standard polycarboxylic acid water-reducing agent produced by Suzhou Sika Company , with a water reduction rate of 20%~40%; the quality is in accordance with the requirements of Concrete Admixtures GB8076-2008 [Considering the size of the components and the spacing of the reinforcement skeleton, the fine aggregate used in the production of concrete is the natural river sand in Yangzhou, intermediate; the coarse aggregate is the crushed stone with a better set of grain sizes of 5~20 mm. The materials are produced by a local sand and gravel plant in Yangzhou, and the main technical parameters are shown in Two groups (three per group) of C30 concrete, C50 concrete, and ECC cubic specimens were cast, respectively, with concrete specimen sizes of 150 mm × 150 mm × 150 mm and an ECC specimen size of 70.7 mm × 77.7 mm × 77.7 mm. Cubic compressive strength tests were conducted, which were synchronized with the beam tests, and the C30 concrete, C50 concrete, and the measured cubic compressive strengths of the ECC were 35.33, 54.45, and 52.85 MPa, respectively. The mix ratios of the ECC and concrete are shown in The test was loaded symmetrically at four points, as shown in Load, strain, displacement, and crack width were measured in the test. The load was displayed and collected in real time by a strain gauge connected to the sensor; the displacement was measured and collected by three percentage meters. Based on the properties of shear damage, it is necessary to establish the placement location of the concrete strain gage paste. Specifically, the strain gages should be arranged equidistantly along the line connecting the loading point and the support point, two strain gages should be positioned at the mid-span of the beam. The loading point is represented by arrows, while the strain gages are denoted by numbers 1 to 8, as illustrated in When the shear span is relatively small, both the RC beam and the concrete–ECC combination beam are damaged by diagonal compression. However, the brittle damage of the RC beam is obvious, such as in beam B1. During the loading process, the surface of the shear span area appears with concrete broken off, and finally, the member is fractured and has obvious dislocation. In beam B15, fewer cracks were produced during the process. Only a major diagonal crack was produced in the area, and there was no warning when the damage occurred. While the concrete at the loading point of the combined beam was damaged, the phenomenon was not obvious, as in beam B15 the phenomenon of surface material shedding did not occur in the shear span area, and it still maintained good integrity. The number of cracks in the shear compression area was much more than in the RC beam, and there are many relatively small diagonal cracks near the location of the main diagonal crack in the limit state that can be seen in the ECC area between the cracks, with fiber bonded to the fractured part. The damage patterns of beams B1 and B15 are shown in When the shear-to-span ratio is moderate, shear damage occurs in the test beam. As in the case of RC beam B18, vertical cracks first appear at the lower edge of the concrete in the tension zone, and the cracks can be seen to extend and widen rapidly once the concrete in the tension zone is cracked. Eventually, the cracks in the diagonal direction run through the cross-section of the RC beam, the concrete in the compression zone between the two loading points is severely broken locally, the crack width in the tension zone is large, and the longitudinal reinforcement is subjected to large yielding or near yielding. While the vertical cracks of the concrete–ECC combination beam do not expand rapidly to the support point after appearing, the number of cracks increases continuously, which limits the expansion of the main cracks well. When the load reaches a certain level, the secondary diagonal cracks in the concrete part grow to form the main diagonal cracks. The diagonal cracks do not penetrate the whole cross-section like the RC beam, but occur in the ECC part to spread into multiple diagonal cracks with smaller widths. The concrete near the loading point is crushed under the action of shear pressure, in which the crack control performance of the ECC with the 100 mm thickness is slightly better than that of the 70 mm thickness, such as beams B7 and B24. The damage patterns of beams B18, B7, and B24 are shown in When the shear span is relatively large, the beam suffers diagonal tensile damage. In the case of RC beam B21, the diagonal crack appears rapidly at the loading point, the concrete surface near the loading point crumbles, the width is visible to the naked eye, and the number of bending zones is small, but the cracks are long. A typical diagonal tensile crack through the whole interface is formed in the direction of the line connecting the loading point and the support point, causing the beam to be pulled off and damaged along the diagonal direction. In contrast, the main diagonal crack of the combined beam is not along the diagonal line. However, bulges above the diagonal line, similar to an arch, and the lower end of the main crack do not extend to the bottom of the beam but are roughly evenly dispersed to disappear at the height of the ECC layer stack, and the damage is accompanied by an obvious “bared” fiber tearing sound, as in the case of beam B14. The damage patterns of beams B21 and B14 are shown in The effect of concrete strength in the compression zone on the shear strength of the concrete–ECC beams is shown in It should be noted that For instance, the compressive strength of the concrete significantly affects the shear strength of the beam during inclined compression damage. Conversely, the tensile properties of the material in the tension zone play a crucial role in the occurrence of inclined tensile damage in the beam. In the context of diagonal compression damage in beams, the influence of concrete compressive strength on beam shear strength is observed to be more pronounced. Conversely, in the case of diagonal tension damage in beams, the tensile properties of the material within the tensile zone exhibit an augmented role, leading to a corresponding decrease in the impact of the concrete compressive strength ,25.When comparing ECC material to concrete, it is seen that ECC material does not exhibit significant advantages in terms of compressive performance. However, it does possess better tensile qualities, making it appropriate for implementation in the tensile zone of beams. This application serves to enhance the shear brittleness of the beam .c, which denotes the compressive stress in the shear-compression zone and is analogous to the compressive properties of the ECC and concrete observed in RC beams; Vaf, indicating the bridging force supplied by fibers at the diagonal cracks; Tsf, representing the combined force of the tensile reinforcement pulling force after fiber reinforcement; and Vdf, signifying the pinning force exerted by the tensile reinforcement and ECC.To examine the shear behavior of concrete–ECC beams, V/(fcbh0); the equation of the relationship between V/(fcbh0) and the shear-to-span ratio isTaking the concrete–ECC beam without web reinforcement as an example, its shear capacity and shear-to-span ratio can be obtained as the dimensionless parameter k1(λ) is shown in Equation (2). The contrast between the equation represented by Equation (2) and the experimental data is seen in Vc was deducted from the shear capacity V to find the shear contribution Vf of ECC; this was performed using the test data obtained from the webless reinforced beams. The resulting connection between Vf and the shear-to-span ratio is represented by Equation (3). The formula for calculating the shear capacity of a webless reinforced concrete–ECC combination beam may be expressed as Equation (4), or more precisely, Equation (5).The test data of the webless beams in this work were evaluated using the program Origin to fit the lower envelope of the data. The resulting relationship of In this study, the impact coefficient of the fiber reinforcing material is denoted as terature  pertainiThe effect of the shear-to-span ratio on the shear-bearing capacity of concrete–ECC beams is shown in The effect of the ECC layer thickness on the shear-bearing capacity of the combined beam is shown in The results of the present study show that, in comparison with RC beams subjected to the same conditions, the average increase in shear capacity for beams with a combination of web reinforcement within the designed shear-to-span ratio is 6%. Additionally, the corresponding increase in the cracking load is 26%. It is worth noting that beams with a hoop ratio of 0.29% exhibit a larger increase with the thickness of the ECC layer. Specifically, when the ECC layer thickness is 100 mm, the mean increase is 9%, whereas, for a thickness of 70 mm, the mean increase is 6%. Conversely, beams with a hoop ratio of 0.42% experience only a 2% increase when the ECC layer thickness is 70 mm, resulting in a 6% increase. The experimental results indicate that the increase in the measured value is 6% for an ECC thickness of 70 mm, while the mean increase in the measured value is only 2% for an ECC thickness of 100 mm. These findings indicate that the augmentation of shear in beams with web reinforcement is more pronounced when the thickness of ECC is increased, particularly at lower hoop rates. However, as the hoop rate increases, the impact of increasing ECC thickness on enhancing the shear capacity diminishes, and in some cases, the shear capacity of certain beams slightly decreases. In terms of cracking load, the outcomes for beams with and without web reinforcement exhibit similar trends.The combined beams with the same other factors but different interface treatments between the ECC and concrete were divided into groups, and the cracking load and ultimate load of 13 groups of beams were compared, as shown in The available FE analysis software ABAQUS was used to build the FE analysis model of the combined ECC–concrete beam. Concrete, ECC material, and mat are selected as C3D8 units. The test beams are supported beams, and the FE model is set up with the same boundary conditions as the test, with the left end support point set as a hinge support and the right end support point set as a sliding support, as shown in In order to simplify the analysis, the principal reinforcement model is an ideal elastoplastic model with the modulus of elasticity and Poisson’s ratio of 200 GPa and 0.3, respectively. The principal model of concrete recommended in the Code for the Design of Concrete Structures, GB 50010-2010 , is usedThe expression of the compressive stress-strain relationship curve is as follows:010-2010 ; ftr, fcThe ECC tensile principal structure model of Han  is used 0, a1, a2, a3, and b0 are fixed constants with fitted values of 0.003, 0.8, 0.66, −0.395, and 43.404, respectively.The ECC compressive principal structure model proposed by Maalej et al.  is used,The load-span displacement curves of each beam obtained from the FE calculations were taken and compared with the experimental results, as shown in (1)From the damage characteristics, the damage type of the combined beam is similar to RC in the same shear-to-span ratio range, but its shear toughness, ability to maintain the integrity of the member, and shear-bearing capacity are improved. The shear-to-span ratio is an important factor affecting the shear-bearing capacity of the member, and with the increase in the shear-to-span ratio, the decrease in the shear force of the combined beam slows down after λ is greater than 2.(2)In the moderate range, ECC thickness can improve the shear performance; the interface treatment of wire mesh and groove has no significant effect on the cracking load and ultimate load size but does increase the experimental complexity and the actual construction difficulty.(3)From the load-deflection curve, the Abaqus simulation results are slightly stiffer than the test results. However, considering the errors brought by external factors in the test conditions and the idealization of the FE simulation by ignoring the bond-slip between materials and the FE software simulation, the error is within a reasonable range; thus, the FE analysis results predicting the ultimate load capacity and deflection are more reasonable.In this paper, the interface treatment, shear-to-span ratio, concrete strength, and ECC thickness are used as parameters to design 36 experimental studies on the shear resistance of ECC–concrete combination beams without web reinforcement, and the following basic conclusions are obtained through comparative studies with Abaqus FE simulation software:


This article presents woven carbon-fiber-reinforced polymer (CFRP) tubular mesh used as a reinforcement on the inner surface of hollow beams made of high-performance concrete (HPC). The tubular mesh was designed to serve as both the tensile and shear reinforcement of hollow beams intended for the construction of small self-supporting structures that could be assembled without mechanization. The reinforcement was prepared with a tri-axial weaving machine from carbon filament yarn and was homogenized using epoxy resin. The interaction of the composite reinforcement with the cementitious matrix was investigated, and the surface of the reinforcement was modified using silica sand and polyvinyl alcohol (PVA) fibers to improve cohesion. The sand coating enhanced bond strength, resulting in the significantly higher flexural strength of the hollow beam of 128%. The PVA fibers had a lower positive effect of 64% on the flexural strength but improved the ductility of the beam. Individual beams were connected by gluing steel parts directly inside the hollow core of the HPC beam. This procedure provides good interaction between the CFRP reinforcement and the glued steel insert and allows for the fast and simple assembly of structures. The weaving of additional layers of the CFRP reinforcement around HPC beams was also explored. A small structure made of the hollow HPC beams with inner composite reinforcement was constructed to demonstrate the possibilities of the presented technology. High-performance concrete (HPC) is widely used not only for its good mechanical properties but also for its aesthetic qualities. Combined with composite reinforcement, HPC can be used in a wide range of applications while being significantly more weight efficient compared to traditional materials, e.g., reinforced concrete. This study focuses on long one-dimensional prefabricated elements, which can be used for the construction of small self-supporting structures. During the development, emphasis was placed on the low weight of the elements and the simple way of joining them so that construction was possible without the use of mechanization. For long one-dimensional elements, which will be mainly subjected to loads induced by their own weight and environment-based loads such as from wind and snow, the prevalent type of load will be in the form of bending, while compressive loads will be minor. Hollow elements are a suitable solution for such conditions, having higher effective depth and elastic section modulus than solid elements of the same weight, and are used as transmission poles ,2 and inThe flexural strength of hollow, traditionally reinforced concrete elements can be equal to the flexural strength of solid elements while having significantly lower weight ,7,8,9. TThis study proposes hollow HPC beams with woven tri-axial carbon fiber composite reinforcement on the inner surface. The composite reinforcement made of carbon fibers is non-corrosive and does not require a concrete cover layer like traditional steel reinforcement ,17. The Regarding the cohesion between reinforcement and concrete, the solution proposed by this study bears a stronger similarity to FRP composite bars. Despite its hollow core and the deviation of the fibers from the longitudinal axis of the composite reinforcement, the outer surface is still the contact zone between concrete and reinforcement and has to be adapted to provide proper interaction. The FRP bars are most commonly wounded, ribbed, or sand-coated to provide the required bond strength ,28,29. FThe main objective of this study was to evaluate the flexural performance of the novel woven CFRP tubular mesh positioned on the inner surface of the hollow HPC beams and the effect of the reinforcement surface modifications on its bond strength with the concrete matrix and on the ductility of the hollow beams. The study also investigated the utilization of the hollow core for the gluing of steel inserts as an option for connecting the elements. Lastly, the process of additive weaving of multiple layers of the composite reinforcement and its effect on the flexural strength of the elements was evaluated. The possible application of the lightweight and durable hollow HPC beams, which can be assembled without mechanization, was demonstrated via the construction of a small structure designed based on all the acquired data.3 according to EN 12390-5:2019 [3 was equal to 49.1 ± 0.3 GPa. All tests were performed using the Controls MCC-Multitest testing machine .The hollow concrete beams take advantage of the fact that the composite reinforcement requires only a minimal concrete cover layer. The concrete cover layer with a thickness of only a few millimeters requires the use of a high-performance fine-grained concrete mixture. The closed structure of the HPC matrix without capillary pores also provides excellent protection against the effects of chlorides, alkalis, and de-icing salts ,34, whic0-5:2019  by three0-5:2019  on prism®-E STS40 F13 24K  with a titer of 1600 tex. The basic parameters of the carbon roving were a tensile strength of 4300 MPa and a modulus of elasticity of 240 GPa, according to the technical data sheet [®  with a tensile strength in bending of 15 MPa and a modulus of elasticity of 2 GPa [The composite reinforcement was prepared by the company Technofiber  using the weaving machine OS 144/1 . The reinforcement was made of carbon rovings Tenaxta sheet . The rovof 2 GPa . The mecAll specimens consisted of an HPC shell, woven tri-axial composite reinforcement, and a hollow core. The woven reinforcement had carbon rovings orientated in two directions with a deviation of ±45° from the longitudinal axis. These rovings were woven on a template with the designed shape and dimensions, usually made of steel. The steel templates had rounded edges to prevent damage to the carbon fibers during weaving. Since the core fibrils of the carbon rovings would not be in direct contact with the concrete matrix, it would not be possible to achieve an effective engagement of all the fibrils, and the tensile strength of the reinforcement would be significantly lower without yarn homogenization . Epoxy r2 content of 99.2% [The surface of the composite reinforcement was modified with different materials to improve the interaction of the composite reinforcement with the concrete matrix. Fine-grained silica sand ST 01/06  with grain sizes from 0.1 mm to 0.6 mm and high SiOof 99.2%  was usedThe manufacturing procedure of the hollow HPC beams is described in The second approach presented at the bottom half of The possibility of utilizing multiple layers of woven composite reinforcement was also explored. In this case, previously prepared hollow concrete beams were used in place of the steel template for weaving a second layer of the composite reinforcement. No separation layer was used to ensure cohesion of the second layer of reinforcement with the inner concrete shell. Epoxy resin impregnation and surface modification using fine-grained silica sand, PVA fibers, or both were applied similarly to the production of the composite reinforcement on the steel template, as illustrated in the second step in It was assumed that the hollow beams would be subjected to stresses mainly induced by bending resulting from their own weight or from other minor loads. Bending stress is one of the best-described behaviors of reinforced and textile-reinforced concrete in real conditions. The testing can be divided into three parts, a four-point bending test to evaluate the effect of different surface modifications of the composite reinforcement, the testing of the developed glued joints of the hollow concrete beams, and a three-point bending test to evaluate the effect of multiple layers of the composite reinforcement. The three-point and four-point bending tests were carried out according to the technical standard EN 12390-5:2019 . All tes2 cross-section, a length of 360 mm, and composite reinforcement woven from 24 carbon rovings. Specimens with composite reinforcement with an unmodified surface and composite reinforcement with a surface modified with ~50 g/m− and ~100 g/m− of fine-grained silica sand had a hollow core with a cross-section of 28 × 28 mm2. Specimens with composite reinforcement surface modified with ~5 g/m− of PVA fibers and a combination of ~5 g/m− of PVA fibers and ~50 g/m− of fine-grained silica sand had a hollow core with a cross-section of 30 × 30 mm2. The difference in the hollow core dimensions was a result of different approaches during specimen preparation.The influence of the surface modifications on the interaction of the inner composite reinforcement with the concrete shell was evaluated using a four-point bending test. The distance between support pins was 300 mm and 100 mm between loading pins, and the testing was performed with a constant increment of displacement of 5 mm/min. Five sets of hollow beam specimens were prepared with a 40 × 40 mm3 with a hollow core of 30 × 30 mm2 and were reinforced with a composite reinforcement with a surface modified with ~5 g/m− of PVA fibers.A solution for connecting the hollow beams was designed via gluing steel parts into the hollow core: either gluing end elements designed for articulated connection to steel structures or gluing elements designed for rigid connection of the hollow beams to each other, for example, in the corners of the structure. A testing setup shown in 2 and a length of 100 mm were designed to fit the specimen hollow cores. Three steel inserts with varying degrees of stiffness were designed to better investigate the behavior of the glued joint and the development of cracks around the end of the steel insert. The inserts with a cross-section of 25 × 25 mm2 cross-section and a length of 160 mm. In this case, the hollow core had a cross-section of only 26 × 26 mm2. The composite reinforcement was woven in variants with 24 and 36 carbon rovings in both the inner and outer layers. Both sets were complemented with reference to only the inner layer of the composite reinforcement with a corresponding number of carbon rovings.A three-point bending test was used to investigate the basic load-bearing characteristics of the hollow beams with multi-layer composite reinforcement. The distance between support pins was 120 mm, and the testing was performed with a constant increment of displacement of 2 mm/min. Four sets of hollow beam specimens were prepared with a 50 × 50 mm− of fine-grained silica sand. There was a significant increase in the transmitted force after the development of the first crack before the reinforcement gradually delaminated from the concrete shell. − of silica sand. Those specimens achieved the highest ultimate flexural strength and had very brittle behavior.The first set of specimens was tested to determine the impact of fine-grained silica sand and structural PVA fibers on the cohesion of the composite reinforcement and the concrete matrix. The surface modifications generally led to a weakening of the thin concrete shell, signified by earlier crack development. The fine-grained silica sand applied on the composite reinforcement surface improved cohesion with the concrete shell. A higher amount of used silica sand correlated with higher flexural strength and more brittle behavior. The composite reinforcement modified with a lower amount of silica sand lost cohesion with the concrete shell more gradually, while the composite reinforcement with a higher amount of silica sand collapsed suddenly without any prior warning. In all cases, the failure of the specimen was caused by the delamination of the composite reinforcement.The results of specimens with PVA fibers used to modify the surface of the composite reinforcement are presented in Due to the variance in the dimensions of the specimens, there are differences in their elastic section moduli and effective depth of cross-section. To complement the force/displacement diagrams, the elastic section moduli, first-cracking and ultimate loads, and calculated first-cracking stress are summarized in The testing of specimens with a glued steel insert with constant stiffness is presented in The testing of all variants yielded very similar results, as given in The last experiment focused on the mechanical performance of the hollow HPC beams with multi-layer composite reinforcement. The results in After the viability of the developed technology was assessed, a small structure made of the hollow HPC beams with inner composite reinforcement was constructed to illustrate the possibilities of the developed technology. The structure shown in 2. The hollow core had a cross-section of 44 × 104 mm2, leaving the HPC concrete shell with a thickness of approximately 8 mm. The composite reinforcement was woven from 24 carbon rovings (1600 tex). Its surface was modified with a combination of PVA fibers and fine-grained silica sand, which achieved both high flexural strength and ductility during testing. The length of both horizontal and vertical elements was 2340 mm.The structure was designed as a combination of load-bearing steel construction, steel glued joints, and hollow HPC elements. The structure was designed from hollow beams and columns of a rectangular cross-section with dimensions of 60 × 120 mmDue to the lightweight elements, the pergola could be assembled without the use of heavy handling equipment. The stability of the pergola was ensured via wind bracing using a stainless-steel wire with a diameter of 5 mm in the vertical plane. The pergola was also equipped with LED lights embedded directly in two of the horizontal hollow beams to provide illumination. The power supply to the LED light was designed to pass through the hollow core of both horizontal and vertical elements.The proposed surface modifications of the inner woven composite reinforcement proved to have a significant effect on the bending behavior of the hollow beams. The composite reinforcement, without any surface modification, proved unsuitable for any application as the unmodified reinforcement delaminated from the HPC shell after crack development. Coating the surface with either fine-grained silica sand or PVA fibers improved bond strength with the cementitious matrix. The sand coating led to higher flexural strength and more brittle behavior, while the elements with the PVA fibers had lower flexural strength and were more ductile. The use of both surface treatments together resulted in an optimal combination of flexural strength and ductility suitable for the proposed long one-dimensional prefabricated elements.Experimental loading showed that the glued joints of the hollow HPC beams using a chemical anchor provided a viable solution for connecting them and equipping them with end elements. The glued connection was reliable, and all specimens failed due to the delamination of the composite reinforcement from the inner surface of the hollow HPC beam. The stiffness of the glued steel insert affected the crack development initiation. The lower stiffness of the insert led to higher flexural strength at first crack development.The hollow HPC elements reinforced with the multi-layer woven composite reinforcement proved not to be viable with the proposed technology. The additive production technology of weaving carbon rovings directly around previously cast HPC elements, and especially the subsequent impregnation of the rovings using epoxy resin, led to the insufficient interaction of the inner and outer concrete shells, which led to the delamination and early failure of the tested specimens.The construction of the small self-supporting structure designed based on the findings of this study demonstrated the feasibility of assembling the hollow concrete elements without the use of mechanization. The use of a chemical anchor for gluing steel joints was proven fast and reliable. The hollow core was also used for the concealed wiring of the LED lights built into the surface of the concrete beams.This study examined and discussed the mechanical performance of the hollow HPC beams with composite reinforcement on their inner surface. The effect of surface modifications of the composite reinforcement was assessed, alongside testing of the connections of the hollow elements and the use of multiple layers of the woven composite reinforcement. The main conclusions of this study are summarized as follows:The presented woven composite reinforcement on the inner surface of the hollow HPC elements had rovings orientated only in two directions, orientated at ±45° from the longitudinal axis. It would also be possible to apply additional rovings in the longitudinal direction. The bending stiffness of such elements would increase significantly. However, no longitudinally oriented rovings were needed for elements designed for the self-supporting structure presented in this study. Further research will focus on the development of 1D elements (columns and beams) with the woven composite reinforcement in combination with longitudinal reinforcement and their use as load-bearing structures.Patent “Lightweight concrete element with textile reinforcement and a method of its production” licensed to CTU in Prague and TECHNOFIBER, s. r. o.