Sural nerve grafts in subacute facial nerve injuries: a report of two cases.

Because facial nerve injuries affect the quality of life, leaving them untreated can have devastating effects. The number of patients with traumatic and iatrogenic facial nerve paralysis is considerably high. Early detection and prompt treatment during the acute injury phase are crucial, and immediate surgical treatment should be considered when complete facial nerve injury is suspected. Symptom underestimation by patients and clinical misdiagnosis may delay surgical intervention, which may negatively affect outcomes and in some cases, impair the recovery of the injured facial nerve. Here, we report two cases of facial nerve injury that were treated with nerve grafts during the subacute phase. In both cases, subacute facial nerve grafting achieved significant improvements. These cases highlight surgical intervention in the subacute phase using nerve grafts as an appropriate treatment for facial nerve injuries.

Identification and characterization of recent retrovirus in Rhinolophus ferrumequinum bats.

An investigation into retrovirus was conducted in six species of bats (Myotis aurascens, Myotis petax, Myotis macrodactylus, Miniopterus fuliginosus, Rhinolophus ferrumequinum, and Pipistrellus abramus) inhabiting South Korea. Exogenous retroviruses (XRVs) were detected in the tissue samples of R. ferrumequinum individuals by PCR assay. Proviruses were identified in all tissue samples through viral quantification using a digital PCR assay per organ (lung, intestine, heart, brain, wing, kidney, and liver), with viral loads varying greatly between each organ. In phylogenetic analysis based on the whole genome, the Korean bat retroviruses and the R. ferrumequinum retrovirus (RfRV) strain formed a new clade distinct from the Gammaretrovirus clade. The phylogenetic results determined these viruses to be RfRV-like viruses. In the Simplot comparison, Korean RfRV-like viruses exhibited relatively strong fluctuated patterns in the latter part of the envelope gene area compared to other gene areas. Several point mutations within this region (6,878-7,774 bp) of these viruses were observed compared to the RfRV sequence. One Korean RfRV-like virus (named Y4b strain) was successfully recovered in the Raw 264.7 cell line, and virus particles replicated in the cells were confirmed by transmission electron microscopy. RfRVs (or RfRV-like viruses) have been spreading since their first discovery in 2012, and the Korean RfRV-like viruses were assumed to be XRVs that evolved from RfRV.IMPORTANCER. ferrumequinum retrovirus (RfRV)-like viruses were identified in greater horseshoe bats in South Korea. These RfRV-like viruses were considered exogenous retroviruses (XRVs) that emerged from RfRV. Varying amounts of provirus detected in different organs suggest ongoing viral activity, replication, and de novo integration in certain organs. Additionally, the successful recovery of the virus in the Raw 264.7 cell line provides strong evidence supporting their status as XRVs. These viruses have now been identified in South Korea and, more recently, in Kenya since RfRV was discovered in China in 2012, indicating that RfRVs (or RfRV-like viruses) have spread worldwide.

Pott's puffy tumor of the upper eyelid misdiagnosed as simple abscess: a case report and literature review.

A 76-year-old woman, initially thought to have a simple abscess on her right upper eyelid, presented to our department of plastic and reconstructive surgery. Enhanced three-dimensional facial computed tomography (CT) revealed an abscess on the right upper lid, with a pyomucocele present in the right frontal sinus, accompanied by bone erosion in the superior wall of the right orbit. Based on the results of the CT scan, we diagnosed an atypical Pott's puffy tumor (PPT) with an abscess on the upper lid originating from the frontal sinusitis. First, surgical incision and drainage were performed in our department, and a percutaneous vacuum drain was placed. To provide a more definitive treatment, endoscopic sinus surgery (ESS) was subsequently performed by otorhinolaryngologists. The patient was discharged without any complications 5 days after ESS. At a 1-year follow-up, no recurrence or notable neurological symptoms were observed. In the case we observed, the patient presented with an upper eyelid abscess and cellulitis, indicating possible orbital involvement. For such patients, a CT scan is necessary. Given the possibility of PPT, it is critical to perform a comprehensive differential diagnosis rather than defaulting to a straightforward approach involving abscess treatment.

Intraosseous vascular malformation of the skull: a case report and literature review.

A 59-year-old woman presented to our clinic with a 3.5× 3-cm protruding mass on her forehead. A skull X-ray revealed a radiolucent osteolytic lesion on the left side of the frontal bone. Additionally, computed tomography showed a 3.1× 1.7× 3.6-cm mass exhibiting a "sunburst" pattern situated between the outer and inner tables of the skull, just superior and lateral to the left frontal sinus. This pattern suggested the presence of an intraosseous vascular malformation (IVM). The lesion was approached via a bicoronal incision. En-bloc resection was performed, removing the mass along with approximately 0.5 cm of the surrounding normal bone without injury to the exposed frontal sinus mucosa. The exposed mucosa was reinforced with a galeal flap, and cranioplasty with bone cement was performed to repair the resulting bony defect. Pathological examination confirmed a diagnosis of intraosseous cavernous-type malformation with mixed cavernous and capillary histological features. We report this case of IVM and review the existing literature, highlighting the satisfactory functional and aesthetic outcomes after surgery.

Genetic characterization and pathogenicity in a mouse model of newly isolated bat-originated mammalian orthoreovirus in South Korea.

Mammalian orthoreoviruses (MRVs) infect a wide range of hosts, including humans, livestock, and wildlife. In the present study, we isolated a novel Mammalian orthoreovirus from the intestine of a microbat (Myotis aurascens) and investigated its biological and pathological characteristics. Phylogenetic analysis indicated that the new isolate was serotype 2, sharing the segments with those from different hosts. Our results showed that it can infect a wide range of cell lines from different mammalian species, including human, swine, and non-human primate cell lines. Additionally, media containing trypsin, yeast extract, and tryptose phosphate broth promoted virus propagation in primate cell lines and most human cell lines, but not in A549 and porcine cell lines. Mice infected with this strain via the intranasal route, but not via the oral route, exhibited weight loss and respiratory distress. The virus is distributed in a broad range of organs and causes lung damage. In vitro and in vivo experiments also suggested that the new virus could be a neurotropic infectious strain that can infect a neuroblastoma cell line and replicate in the brains of infected mice. Additionally, it caused a delayed immune response, as indicated by the high expression levels of cytokines and chemokines only at 14 days post-infection (dpi). These data provide an important understanding of the genetics and pathogenicity of mammalian orthoreoviruses in bats at risk of spillover infections.IMPORTANCEMammalian orthoreoviruses (MRVs) have a broad range of hosts and can cause serious respiratory and gastroenteritis diseases in humans and livestock. Some strains infect the central nervous system, causing severe encephalitis. In this study, we identified BatMRV2/SNU1/Korea/2021, a reassortment of MRV serotype 2, isolated from bats with broad tissue tropism, including the neurological system. In addition, it has been shown to cause respiratory syndrome in mouse models. The given data will provide more evidence of the risk of mammalian orthoreovirus transmission from wildlife to various animal species and the sources of spillover infections.

High Performance Concretes with Highly Reactive Rice Husk Ash and Silica Fume.

The search for new sources of high-quality non-crystalline silica as a construction material for high-performance concrete has attracted the interest of researchers for several decades. Numerous investigations have shown that highly reactive silica can be produced from rice husk, an agricultural waste that is abundantly available in the world. Among others, the production of rice husk ash (RHA) by chemical washing with hydrochloric acid prior to the controlled combustion process has been reported to provide higher reactivity because such a process removes alkali metal impurities from RHA and provides an amorphous structure with higher surface area. This paper presents an experimental work in which a highly reactive rice husk ash (TRHA) is prepared and evaluated as a replacement for Portland cement in high-performance concretes. The performance of RHA and TRHA was compared with that of conventional silica fume (SF). Experimental results showed that the increase in compressive strength of concrete with TRHA was clearly observed at all ages, generally higher than 20% of the strength obtained with the control concrete. The increase in flexural strength was even more significant, showing that concrete with RHA, TRHA and SF increased by 20%, 46%, and 36%, respectively. Some synergistic effect was observed when polyethylene-polypropylene fiber was used for concrete with TRHA and SF. The chloride ion penetration results also indicated that the use of TRHA had similar performance compared to that of SF. Based on the results of statistical analysis, the performance of TRHA is found to be identical to that of SF. The use of TRHA should be further promoted considering the economic and environmental impact that will be achieved by utilizing agricultural waste.

Determination of the Predictors with the Greatest Influence on Walking in the Elderly.

Background and Objectives: Previous studies have revealed that independent variables (lower extremity strength, postural control ability, and body composition) influence gait performance and variability, but the difference in the relative influence between these variables is unclear. Hence, this study determines the variable that is the most influential predictor of gait performance and variability among potential independent variables in the elderly. Materials and Methods: Seventy-eight subjects aged ≥60 years participated. For each subject, the gait variables and lower extremity muscle strength were measured using an accelerometer worn on both feet during a 6-minute walk and a manual force sensor, respectively. The static balance ability was measured through two force plates, and the body composition was measured by applying bioelectrical impedance analysis. Linear regression analyses were performed stepwise to determine whether these variables affect gait performance and variability. Results: After adjusting for sex and gait performance, the ankle strength, body fat mass, mean velocity in the medial-lateral direction, ankle plantar flexion strength, and girth were predictors of gait speed dorsiflexion, gait performance, swing width of the gait performance, walking speed, and gait variability, respectively. Conclusions: Overall, gait performance in the elderly is related to muscle strength, postural control, and body composition in a complex manner, but gait variability appears to be more closely related to ankle muscle strength. This study provides further evidence that muscle strength is important in motor function and stability.

Self-directed learning quotient and common learning types of pre-medical students in Korea by the Multi-Dimensional Learning Strategy Test 2nd edition: a descriptive study.

This study aimed to find the self-directed learning quotient and common learning types of pre-medical students through the confirmation of 4 characteristics of learning strategies, including personality, motivation, emotion, and behavior. The response data were collected from 277 out of 294 target first-year pre-medical students from 2019 to 2021, using the Multi-Dimensional Learning Strategy Test 2nd edition. The most common learning type was a self-directed type (44.0%), stagnant type (33.9%), latent type (14.4%), and conscientiousness type (7.6%). The self-directed learning index was high (29.2%), moderate (24.6%), somewhat high (21.7%), somewhat low (14.4%), and low (10.1%). This study confirmed that many students lacked self-directed learning capabilities for learning strategies. In addition, it was found that the difficulties experienced by each student were different, and the variables resulting in difficulties were also diverse. It may provide insights into how to develop programs that can help students increase their self-directed learning capability.

The Effect of Changes in the Separation Process for the Performance of Recycled Cement Powder: A Comparison with a Previous Study for Radioactive Waste Immobilization.

Separation of hydrated cement paste from aggregate is a key technology to reduce the amount of radioactive concrete waste during the decommissioning process. If separated cement-paste portions can be recycled as a solidifying agent for other radioactive waste, the amount of radioactive concrete waste could be close to "zero". A study was conducted to achieve circular economy in the area of concrete decommissioning and found it to be successfully used as a solidifying agent for immobilization of liquid radioactive waste. However, previous work used a process that requires large amounts of energy (heat treatment was applied to most of the concrete fraction) because the objective was to completely remove hydrated cement powder from the aggregate. In this work, the separation system was modified to increase energy efficiency (heat treatment was applied to separated powder only), but such a change decreased the surface area of the recycled cement powder due to a higher inclusion of aggregate powder. A relatively lower solution to binder ratio could have been achieved for the preparation of wasteform specimens, and as a result, a 28 day compressive strength of wasteform could have become higher, but the final leachability indices were lower than the results observed from previous work. The results from 28 day compressive strength, thermal cycling and 90 day leaching experiments met the acceptance criteria for wasteform, indicating that this modified system can also be used for immobilization of liquid radioactive waste to meet the "zero" production of concrete waste during the decommissioning of a nuclear power plant. It should be noted that accurate monitoring of aggregate content in recycled cement powder during production is important to maintain proper reactivity of recycled cement powder.

First Isolation of Pseudogymnoascus destructans, the Fungal Causative Agent of White-Nose Syndrome, in Korean Bats (Myotis petax)

White-nose syndrome (WNS), caused by Pseudogymnoascus destructans (Pd), is a lethal fungal disease that affects hibernating bats in North America. Recently, the presence of Pd was reported in countries neighboring Korea. However, Pd has not been investigated in Korea. Therefore, this study aimed to identify the presence of Pd in Korean bats. Altogether, wings from 241 bats were collected from 13 cities and cultured. A total of 79 fungal colonies were isolated, and two isolates were identified as Pd using polymerase chain reaction. Of the nine bat species captured in 13 cities, Pd was isolated only from Myotis petax in Goryeong. Atypical, curved conidia were observed in two isolated fungal colonies. Although histological lesions were not observed by hematoxylin and eosin or periodic acid−Schiff staining, fungal invasion was observed in the tissue sections. Taken together, these results confirmed the presence of Pd in Korean bats and suggest the possibility of WNS outbreaks in Korean bats. This is the first report of the isolation and molecular analysis of Pd from Korean bats.

Efficacy and safety of equine cartilage for rhinoplasty: a multicenter double-blind non-inferiority randomized confirmatory clinical trial.

BACKGROUND: The efficacy and safety of equine cartilage as a competent xenograft material for rhinoplasty were evaluated and compared to the outcomes of rhinoplasty using silicone implants. METHODS: We performed a multicenter, double-blind, non-inferiority, and randomized confirmatory study. Fifty-six patients were randomized 1:1 to the study group (using MegaCartilage-E) and control group (using silicone implants). The Rhinoplasty Outcome Evaluation (ROE) score, photo documentation, Global Aesthetic Improvement Scale (GAIS), and adverse event data were obtained until 12 months after surgery. The primary efficacy, which is the change in ROE score 6 months after surgery, was assessed in the modified intention-to-treat set. The secondary efficacy was evaluated in the per-protocol set by assessing the change in ROE score 6 and 12 months after surgery and nasofrontal angle, the height of the nasion, and GAIS 1, 6, and 12 months after surgery. RESULTS: The change in ROE score of the study group was non-inferior to that of the control group; it increased by 24.26 ± 17.24 in the study group and 18.27 ± 17.60 in the control group (p = 0.213). In both groups, all secondary outcome measures increased, but there was no statistical difference. In the safety set, treatment-emergent adverse events occurred in 10 patients (35.71%) in the study group and six patients (21.43%) in the control group (p = 0.237). There were 13 adverse device events in the study group and six adverse device events in the control group (p = 0.515). CONCLUSION: Processed equine cartilage can be used effectively and safely as xenograft material for rhinoplasty.

A computed tomography-based analysis of the structure of the mandible according to age and sex.

BACKGROUND: The primary objectives of mandibular surgery are to achieve optimal occlusion, low sensory disturbance, and adequate fixation with early movement. In-depth knowledge of the mandibular structure is required to achieve these goals. This study used computed tomography (CT) to evaluate the mandibular cortical thickness and cancellous space according to age and sex. METHODS: We enrolled 230 consecutive patients, aged 20 to 50 years, who underwent CT scanning. The cortex and cancellous space centered around the inferior alveolar nerve (IAN) canal were measured at two specific locations: the lingula and second molar region. Statistical analysis of differences according to increasing age and sex was performed. RESULTS: The t-test revealed that the cancellous space and cortical thickness differed significantly with respect to the threshold of 35 years of age. Both cortical thickness and cancellous space in the molar region were negatively correlated with age. Meanwhile, both cortical thickness and cancellous space in the lingula region showed a positive correlation with age. With respect to sex, significant differences in the cancellous space at the molar region and the cortical thickness at the lingula were observed. However, no further statistically significant differences were observed in other variables with respect to sex. The sum of each measurement on the mandibular body reflected the safe distance from the surface of the outer cortex to the IAN canal. The safe distances also showed statistically significant differences between those above and below 35 years of age. CONCLUSION: Knowledge of the anatomical structure of the mandible and of changes in bone structure is crucial to ensure optimal surgical outcomes and avoid damage to the IAN. CT examination is useful to identify changes in the bone structure, and these should be taken into account in the planning of surgery for older patients.

Comparison of clinical characteristics and outcomes of hospitalized patients with seasonal coronavirus infection and COVID-19: a retrospective cohort study.

BACKGROUND: Unlike SARS-CoV and MERS-C0V, SARS-CoV-2 has the potential to become a recurrent seasonal infection; hence, it is essential to compare the clinical spectrum of COVID-19 to the existent endemic coronaviruses. We conducted a retrospective cohort study of hospitalized patients with seasonal coronavirus (sCoV) infection and COVID-19 to compare their clinical characteristics and outcomes. METHODS: A total of 190 patients hospitalized with any documented respiratory tract infection and a positive respiratory viral panel for sCoV from January 1, 2011, to March 31, 2020, were included. Those patients were compared with 190 hospitalized adult patients with molecularly confirmed symptomatic COVID-19 admitted from March 1, 2020, to May 25, 2020. RESULTS: Among 190 patients with sCoV infection, the Human Coronavirus-OC93 was the most common coronavirus with 47.4% of the cases. When comparing demographics and baseline characteristics, both groups were of similar age (sCoV: 74 years vs. COVID-19: 69 years) and presented similar proportions of two or more comorbidities (sCoV: 85.8% vs. COVID-19: 81.6%). More patients with COVID-19 presented with severe disease (78.4% vs. 67.9%), sepsis (36.3% vs. 20.5%), and developed ARDS (15.8% vs. 2.6%) compared to patients with sCoV infection. Patients with COVID-19 had an almost fourfold increased risk of in-hospital death than patients with sCoV infection (OR 3.86, CI 1.99-7.49; p < .001). CONCLUSION: Hospitalized patients with COVID-19 had similar demographics and baseline characteristics to hospitalized patients with sCoV infection; however, patients with COVID-19 presented with higher disease severity, had a higher case-fatality rate, and increased risk of death than patients with sCoV. Clinical findings alone may not help confirm or exclude the diagnosis of COVID-19 during high acute respiratory illness seasons. The respiratory multiplex panel by PCR that includes SARS-CoV-2 in conjunction with local epidemiological data may be a valuable tool to assist clinicians with management decisions.

Clinical characteristics and outcomes of the first two waves of the COVID-19 pandemic in a community hospital: a retrospective cohort study.

Objective: To describe the clinical characteristics and outcomes of two waves of the COVID-19 pandemic. Methods: A de-identified dataset of patients with COVID-19 admitted to our community hospital in Evanston, Illinois, from March 1, 2020 to February 28, 2021 was retrospectively reviewed. Patients from the first wave were identified as those admitted during the initial peak of admissions observed at our hospital between March 1, 2020 and September 3, 2020. The second wave was defined as those admitted during the second peak of admissions observed between October 1, 2020 and February 28, 2021. Results: In total, 671 patients were included. Of these, 399 (59.46%) were identified as patients from the first wave and 272 (40.54%) as patients from the second wave. Significantly more patients received steroids (86.4% vs 47.9%, p < 0.001), remdesivir (59.6% vs 9.5%, p < 0.001), humidified high-flow nasal cannula (18% vs 6.5%, p < 0.001), and noninvasive ventilation (11.8% vs 3.3%, p < 0.001) during the second wave. Patients from the first wave had a greater hazard for death compared with patients from the second wave (hazard ratio [HR] 1.62, 95% CI 1.08-2.43; p = 0.019). Conclusion: Among patients hospitalized with COVID-19 in our community hospital, there was a decrease in case-fatality rate in the second surge of the COVID-19 pandemic compared with the first wave.

Is partial hepatectomy a curable treatment option for hepatocellular carcinoma accompanied by cirrhosis? A meta-analysis and cure model analysis.

BACKGROUNDS/AIMS: It is challenging to assess the efficacy of partial hepatectomy (PH) as a treatment option for patients with hepatocellular carcinoma (HCC) accompanied by cirrhosis. This study aimed to determine the cure fraction of PH for HCC accompanied by cirrhosis compared to that for HCC without cirrhosis. METHODS: A systematic review was performed on outcomes of previous studies that compared recurrence-free survival (RFS) after PH in patients with HCC with or without cirrhosis. A meta-analysis was conducted to obtain the cumulative hazard ratio for two patient groups: cirrhosis and non-cirrhosis. Cure fractions after PH in both groups were determined using a cure model analysis. RESULTS: A total of 18 studies were eligible for meta-analysis and 13 studies were selected for the cure model analysis. The cumulative hazard ratio for RFS of the cirrhosis group compared to that of the non-cirrhosis group was 1.66 (95% confidence interval [CI], 1.43-1.93). Survival data of 3,512 patients in both groups were reconstructed from survival curves of original articles for cure model analysis. The probability of being statistically cured after PH for HCC was 14.1% (95% CI, 10.6%-18.1%) in the cirrhosis group lower than that (32.5%) in the non-cirrhosis group (95% CI, 28.6%-36.4%). CONCLUSIONS: The prognosis after PH for HCC accompanied by cirrhosis is inferior to that for HCC without cirrhosis. However, a cure can be expected for one-seventh of patients with HCC accompanied by cirrhosis after PH.

Genetic diversity of bat coronaviruses and comparative genetic analysis of MERS-related coronaviruses in South Korea.

Bats have been identified as a natural reservoir of several potentially zoonotic viruses, including Lyssavirus, Ebola virus, Marburg virus, Hendra virus, Nipah virus, as well as severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus (CoV). Here, we performed a molecular epidemiological investigation of South Korean bat viruses. Genetic comparative analysis was performed on the spike glycoprotein gene of the detected MERS-related CoVs. Among 1640 samples (348 oral swabs, 1199 faecal samples, 83 urine samples and 10 bat carcass) collected across 24 South Korean provinces during 2017-2019, CoV was detected in 82 samples (75 faeces and seven oral swab samples) from 11 provinces. Surveillance over the 3 years during which samples were collected revealed significantly higher CoV detection rates between spring and autumn, and a high detection rate in Vespertillionidae and Rhinolophidae bats. Our phylogenetic analysis shows that Korean bat CoVs are genetically diverse regardless of their spatiotemporal distribution and their host species, and that the discovered bat CoVs belong to various subgenera within the Alpha- and Betacoronavirus genera. Twenty detected MERS-related CoVs belonging to the genus Betacoronavirus were similar to the Ia io bat CoV NL140422 and NL13845 strains. A comprehensive genetic analysis of two Korean bat MERS-related CoV spike receptor binding domain (RBDs) (176 and 267 strains) showed that the 18 critical residues that are involved in interactions with the human DPP4 receptor are most similar to the NL13845 strain, which is known to not bind with hDPP4. A deeper analysis of the interfacing residues in the Korean bat MERS-related CoVs RBD-hDPP4 complexes showed that the Korean bat CoVs has fewer polar contacts than the NL13845 strain. Although further study will be needed, these results suggest that Korean bat MERS-related CoVs are unlikely to bind with hDPP4. Nevertheless, these findings highlight the need for continuous monitoring to identifying the origin of new infectious diseases, specifically mutant CoV.

Newly appointed medical faculty members' self-evaluation of their educational roles at the Catholic University of Korea College of Medicine in 2020 and 2021: a cross-sectional survey-based study.

This study aimed to investigate the degree to which newly appointed medical faculty members at the Catholic University of Korea are aware of Harden and Crosby's 12 educational roles and to identify their preferred educational roles. A 12-item survey questionnaire was distributed to 110 participants, and 100 responses were included in the analysis. The respondents gave the highest score to "clinical or practical teacher" and the lowest score to "curriculum planner" for their current personal competencies. For their preferred personal future competencies, they assigned the highest score to "on the job role model" and the lowest score to "student assessor." They gave almost equally high values to all 12 roles. However, individual faculty members had different preferences for educational roles. Accordingly, medical schools need to plan and implement customized faculty development programs, and efforts to provide appropriate educational roles according to individual faculty members' preferences are needed.

Genomic Characterization of a Novel Alphacoronavirus Isolated from Bats, Korea, 2020.

Coronavirus, an important zoonotic disease, raises concerns of future pandemics. The bat is considered a source of noticeable viruses resulting in human and livestock infections, especially the coronavirus. Therefore, surveillance and genetic analysis of coronaviruses in bats are essential in order to prevent the risk of future diseases. In this study, the genome of HCQD-2020, a novel alphacoronavirus detected in a bat (Eptesicus serotinus), was assembled and described using next-generation sequencing and bioinformatics analysis. The comparison of the whole-genome sequence and the conserved amino acid sequence of replicated proteins revealed that the new strain was distantly related with other known species in the Alphacoronavirus genus. Phylogenetic construction indicated that this strain formed a separated branch with other species, suggesting a new species of Alphacoronavirus. Additionally, in silico prediction also revealed the risk of cross-species infection of this strain, especially in the order Artiodactyla. In summary, this study provided the genetic characteristics of a possible new species belonging to Alphacoronavirus.

An Elaborate New Linker System Significantly Enhances the Efficacy of an HER2-Antibody-Drug Conjugate against Refractory HER2-Positive Cancers.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in breast and gastric cancers and this causes poor clinical outcomes. Although both T-DM1 and Enhertu are approved as an HER2-targeting antibody-drug conjugate (ADC), the effects of these drugs are still not satisfactory to eradicate diverse tumors expressing HER2. To address this shortfall in HER2-targeted therapeutics, an elaborate cleavable linker is created and a novel HER2-targeting ADC composed with trastuzumab and monomethyl auristatin F, which is being investigated in a phase 1 clinical trial and is referred to as LegoChem Bisciences-ADC (LCB-ADC). LCB-ADC displays a higher cytotoxic potency than T-DM1 and it also has a higher G2/M arrest ratio. In animal studies, LCB-ADC produces noticeable tumor growth inhibition compared with trastuzumab or T-DM1 in an HER2 high-expressing N87 xenograft tumor. Especially, LCB-ADC shows good efficacy in terms of suppressing tumor growth in a patient-derived xenograft (PDX) model of HER2-positive gastric cancer as well as in T-DM1-resistant models such as HER2 low-expressing HER2 low expressing JIMT-1 xenograft tumor and PDX. Collectively, the results demonstrate that LCB-ADC with the elaborate linker has a higher efficacy and greater biostability than its ADC counterparts and may successfully treat cancers that are nonresponsive to previous therapeutics.