High-temperature concomitant metal-insulator and spin-reorientation transitions in a compressed nodal-line ferrimagnet Mn3Si2Te6.

Symmetry-protected band degeneracy, coupled with a magnetic order, is the key to realizing novel magnetoelectric phenomena in topological magnets. While the spin-polarized nodal states have been identified to introduce extremely-sensitive electronic responses to the magnetic states, their possible role in determining magnetic ground states has remained elusive. Here, taking external pressure as a control knob, we show that a metal-insulator transition, a spin-reorientation transition, and a structural modification occur concomitantly when the nodal-line state crosses the Fermi level in a ferrimagnetic semiconductor Mn3Si2Te6. These unique pressure-driven magnetic and electronic transitions, associated with the dome-shaped Tc variation up to nearly room temperature, originate from the interplay between the spin-orbit coupling of the nodal-line state and magnetic frustration of localized spins. Our findings highlight that the nodal-line states, isolated from other trivial states, can facilitate strongly tunable magnetic properties in topological magnets.

Exploring Molecular Genetic Alterations and RAF Fusions in Melanoma: A Belvarafenib Expanded Access Program in Patients with RAS/RAF-Mutant Melanoma.

BACKGROUND: Melanoma incidence is on the rise in East Asia, yet studies of the molecular landscape are lacking in this population. We examined patients with melanoma who underwent next-generation sequencing (NGS) at a single tertiary center in South Korea, focusing on patients harboring NRAS or RAF alterations who received belvarafenib, a pan-RAF dimer inhibitor, through the Expanded Access Program (EAP). PATIENTS AND METHODS: Data were collected from 192 patients with melanoma who underwent NGS between November 2017 and May 2023. Variant call format data were obtained and annotated. Patients in the EAP received 450 mg twice daily doses of belvarafenib. RESULTS: Alterations in the RAS/RTK pathway were the most prevalent, with BRAF and NRAS alteration rates of 22.4% and 17.7%, respectively. NGS enabled additional detection of fusion mutations, including 6 BRAF and 1 RAF1 fusion. Sixteen patients with NRAS or RAF alterations received belvarafenib through the EAP, and disease control was observed in 50%, with 2 patients demonstrating remarkable responses. CONCLUSIONS: Our study highlights the value of NGS in detecting BRAF, NRAS mutations and RAF fusions, expanding possibilities for targeted therapies in malignant melanoma. Belvarafenib showed clinical benefit in patients harboring these alterations. Ongoing trials will provide further insights into the safety and efficacy of belvarafenib.

An Ab Initio Study of the Origin of Structural Stability in P2-NaMnO2 with Li Doping at High Voltage.

P2-type sodium cathode materials generally exhibit a P2-O2 phase transition upon deintercalation at high voltage, which is detrimental to their cycling performance. Herein, using first-principles calculations, we investigate the structural stability and phase transition of P2-Na0MnO2 upon substitution of Li for Mn as a model of a high-voltage phase. The phonon of P2-Na0MnO2 shows an imaginary phonon frequency, indicating instability, which is consistent with the experimental P2-O2 transformation. On the contrary, the phonon of P2-Na0Li0.25Mn0.75O2 shows dynamic stability. We demonstrate that the substitution of the Li ion induces the redistribution of charge from the out-of-plane to in-plane orbitals along with a reduced charge of oxygen. Furthermore, we consider the various Li doping compositions and suggest that the density of the next-nearest-neighbor Li-ion pairs also plays an important role in stabilizing the P2 phase. On the basis of our findings, we propose a minimum of ∼20% Li doping to stabilize P2-NaLixMn1-xO2 at high voltage.

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial.

PURPOSE: Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial. MATERIALS AND METHODS: The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)-based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis. RESULTS: Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable. CONCLUSION: Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Decreased SMP30 Expression Is Related With EMT in the Kidneys of Two Siberian Tigers With CKD.

BACKGROUND/AIM: Chronic kidney disease (CKD) is one of the most common causes of mortality in wild non-domestic felidae. The molecular mechanism regulating renal fibrosis in nephropathy is not fully understood especially in the felidae. This study aimed to elucidate senescence marker protein 30 (SMP30) expression patterns and its relationship with epithelial-mesenchymal transition (EMT) by immunostaining in two necropsied Siberian tigers (Panthera tigris altaica) with CKD. MATERIALS AND METHODS: Two kidney samples from male Siberian tigers were fixed and tissue sections were stained for histopathological assay. RESULTS: In CKD, renal tubular epithelial cells lost their tubular structures surrounded by severe interstitial fibrosis and were detached from the basement membrane. These damaged cells resembled the morphology of mesenchymal cells and showed much lower SMP30 expression compared with intact tubular epithelial cells. These cells also expressed vimentin, which is specifically expressed by mesenchymal cells, and through double staining, it was observed that vimentin was expressed in the tubular epithelial cells where SMP30 was not expressed. In addition, double-positive expression of pan-cytokeratin (pan-CK) and vimentin was found in damaged epithelial cells with mesenchymal features. CONCLUSION: We demonstrated possible evidence to understand the role of SMP30 as a new pivotal factor and the possibility of decreased SMP30 as a potential indicator of EMT at the end stage of CKD.

Evaluating the cost utility of estradiol plus dydrogesterone for the treatment of menopausal women in China.

AIM: Evaluate the cost utility of menopausal hormone therapy for women in China. MATERIALS AND METHODS: A bespoke Markov cost utility model was developed to evaluate a cohort of symptomatic perimenopausal women (>45 years) with intact uterus in China in accordance with China's Pharmacoeconomic guideline. Short (5-year) and long (10-year) treatment durations were evaluated over a lifetime model time horizon with 12-month cycle duration. Societal and healthcare payer perspectives were evaluated in the context of a primary care provider/prescriber, outpatient setting with inpatient care for patients with chronic conditions. Disease risk and mortality parameters were derived from focused literature searches, and China Diagnosis-related Group cost data was included. Comprehensive scenario, univariate and probabilistic sensitivity analysis were undertaken along with independent validation. This is the first model to include MHT-related disease risks. RESULTS: According to base case results, the total cost for MHT was 22,516$ (150,106¥) and total quality adjusted life years 12.32 versus total cost of no MHT 30,824$ (205,495¥) and total quality adjusted life years 11.16 resulting in a dominant incremental cost effectiveness ratio of -7,184$ (-47,898¥) per QALY. Results hold true over a range of univariate deterministic sensitivity and scenario analyses. Probabilistic analysis showed a 91% probability of being cost effective at a willingness to pay threshold of three times Gross Domestic Product per capita in China. CONCLUSION: Contingent on the structure and assumptions of the model, combination of estradiol plus dydrogesterone MHT is potentially cost saving in symptomatic women over the age of 45 years in China.

Menopausal hormone therapy is publicly funded in many countries to alleviate symptoms of menopause; however, uptake has been comparatively slow in China. This has implications for the estimated 168 million menopausal-aged women. This analysis is the first to evaluate the cost effectiveness of menopausal hormone therapy in China using best practice principles and incorporating longer term disease risks. Menopausal hormone therapy is potentially cost saving in the context of China.

Molecular Detection and Genotyping of Theileria spp. in Deer (Cervidae) in Korea.

Major clinical symptoms of Theileria infection include fever, anemia, anorexia, jaundice, and decreased milk production. Although several studies have been conducted on tick-borne pathogens, including Theileria in Korea, only a few have focused on Theileria infection in deer, including the Korean water deer. Blood samples from 160 deer were collected and subjected to DNA extraction and polymerase chain reaction (PCR). Next, PCR-positive samples were sequenced and analyzed by constructing a phylogenetic tree. The results showed that the overall infection rate of Theileria was 8.1% (13/160). Infection rates of 100% were observed in the northern and southern regions. However, the study's limitation was its small sample size, wherein five and one samples were analyzed from the northern and southern regions, respectively. The central region exhibited the lowest infection rate of 2.9% (4/140). Infection rates also differed based on seasons, with the highest (18.4%, 9/49) being observed in spring, followed by that in summer (8.9%, 4/45). However, no infection was observed during autumn and winter. A phylogenetic analysis indicated that the PCR-positive samples contained Theileria luwenshuni, which usually infects small ruminants, such as goats and sheep.

Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage: A Single-Institute Study in South Korea.

PURPOSE: Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide. National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC. MATERIALS AND METHODS: We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the "before COVID" period, and the years 2020 and 2021 as the "during COVID" period. RESULTS: Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it. Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years. CONCLUSIONS: During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.

A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13).

BACKGROUND: c-KIT mutations are found in approximately 15% of patients with malignant melanoma in the Asian population. Regorafenib, an oral multikinase inhibitor, acts against both wild-type and mutant KIT. OBJECTIVE: This multi-institutional, phase II, single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harbouring c-KIT mutations. METHODS: Patients with metastatic melanoma positive for c-KIT mutations, upon progression after at least one line of systemic treatment, were enroled. Patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was disease control rate (DCR), and secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 23 patients were enrolled. c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving complete response, 5 (21.7%) achieving partial response, and 10 (43.5%) showing stable disease. ORR was 30.4% (7/23). The median follow-up period was 15.7 months (95% confidence interval [CI], 9.6-21.3), and median OS and PFS were 21.5 months (95% CI, 15.1-27.9) and 7.1 months (95% CI, 5.0-9.2), respectively. Circulating tumour DNA analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumour mutational profiles. The most common adverse events (AEs) were skin reactions, including palmar-plantar erythrodysesthesia (52.2%), and grade 3 AEs were reported in 39.1% (9/23) of the patients. CONCLUSION: Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harbouring c-KIT mutations.

The anti-platelet activity of panaxadiol fraction and panaxatriol fraction of Korean Red Ginseng in vitro and ex vivo.

Background: The anti-platelet activity of the saponin fraction of Korean Red Ginseng has been widely studied. The saponin fraction consists of the panaxadiol fraction (PDF) and panaxatriol fraction (PTF); however, their anti-platelet activity is yet to be compared. Our study aimed to investigate the potency of anti-platelet activity of PDF and PTF and to elucidate how well they retain their anti-platelet activity via different administration routes. Methods: For ex vivo studies, Sprague-Dawley rats were orally administered 250 mg/kg PDF and PTF for 7 consecutive days before blood collection via cardiac puncture. Platelet aggregation was conducted after isolation of the washed platelets. For in vitro studies, washed platelets were obtained from Sprague-Dawley rats. Collagen and adenosine diphosphate (ADP) were used to induce platelet aggregation. Collagen was used as an agonist for assaying adenosine triphosphate release, thromboxane B2, serotonin, cyclic adenosine monophosphate, and cyclic guanosine monophosphate (cGMP) release. Results: When treated ex vivo, PDF not only inhibited ADP and collagen-induced platelet aggregation, but also upregulated cGMP levels and reduced platelet adhesion to fibronectin. Furthermore, it also inhibited Akt phosphorylation induced by collagen treatment. Panaxadiol fraction did not exert any anti-platelet activity in vitro, whereas PTF exhibited potent anti-platelet activity, inhibiting ADP, collagen, and thrombin-induced platelet aggregation, but significantly elevated levels of cGMP. Conclusion: Our study showed that in vitro and ex vivo PDF and PTF treatments exhibited different potency levels, indicating possible metabolic conversions of ginsenosides, which altered the content of ginsenosides capable of preventing platelet aggregation.

Application of 3D-printed prosthetic lower beak in an Oriental stork (Ciconia boyciana).

To our knowledge, ours is the first case of applying a 3D-printed prosthetic beak to an Oriental stork (Ciconia boyciana). A stork in captivity underwent several surgeries for beak fractures, but the lower-mandible fractures failed to be repaired. Therefore, we applied a patient-specific beak prosthesis of titanium alloy and nylon. Because the prosthetic beak could not be maintained due to mandible and soft-tissue inflammation, the stork was euthanized. Still, we confirmed typical behavior and feeding for ~3 months after surgery. This report highlights some of the challenges we encountered and identifies process improvements required for a more successful surgery.

Enhanced thermoelectric performance of SnSe by controlled vacancy population.

The thermoelectric performance of SnSe strongly depends on its low-energy electron band structure that provides high density of states in a narrow energy window due to the multi-valley valence band maximum (VBM). Angle-resolved photoemission spectroscopy measurements, in conjunction with first-principles calculations, reveal that the binding energy of the VBM of SnSe is tuned by the population of Sn vacancy, which is determined by the cooling rate during the sample growth. The VBM shift follows precisely the behavior of the thermoelectric power factor, while the effective mass is barely modified upon changing the population of Sn vacancies. These findings indicate that the low-energy electron band structure is closely correlated with the high thermoelectric performance of hole-doped SnSe, providing a viable route toward engineering the intrinsic defect-induced thermoelectric performance via the sample growth condition without an additional ex-situ process.

Molecular epidemiology of Toxoplasma gondii in cattle in Korea.

Toxoplasmosis is a major public health concern, with raw or undercooked meat being the primary source of human infection. Knowledge regarding the molecular epidemiology of Toxoplasma gondii in cattle destined for human consumption in Korea is lacking. The present study aimed to genetically characterize the infectious strains of T. gondii. Overall, 455 cattle blood samples from 84 farms in the Gyeongnam-do (Province) were randomly collected in 2017. Nested PCR analysis revealed that only 3 (0.7%) samples were infected with T. gondii. The B1 gene sequence of T. gondii was observed to be similar (97.3-99.6%) to that of other T. gondii isolates. This is the first study to perform the molecular detection of T. gondii in cattle in Korea. Although the prevalence of infection was low, our findings suggest that cattle present a potential public health issue. It may be crucial to recognize the importance of T. gondii infection in cattle meat.

Molecular analysis of Rickettsia spp. and related tick-borne pathogens detected in dogs in Korea.

Ticks are widespread in nature and serve as primary vectors for several tick-borne pathogens (TBPs). Ticks and TBPs cause considerable harm to humans and animals and have emerged as a major global public health concern. Domestic dogs are the major reservoirs of zoonotic agents owing to their constant interaction with humans. This study aimed to assess the prevalence and risk factors of canine TBPs, such as Rickettsiales, Coxiella burnetii, hepatozoa, and Borrelia spp., using molecular analyses. A total of 906 dogs were examined and 4 TBPs were identified: Anaplasma phagocytophilum (5; 0.6%), Hepatozoon canis (9; 1.0%), Candidatus Rickettsia longicornii (2; 0.2%), and Rickettsia tamurae (1; 0.1%). Ehrlichia spp., C. burnetii, and Borrelia spp. were not detected. To the best of our knowledge, this is the first study to perform a phylogenetic analysis of Candidatus R. longicornii and R. tamurae in dogs. These findings can help determine the potential public health risks by enhancing our understanding of the geographical and vector distributions of TBPs in Korea.

Tick Populations and Molecular Analysis of Anaplasma Species in Ticks from the Republic of Korea.

The present study was performed to survey the dominant tick populations and molecularly determine the pathogenic agents of anaplasmosis in ticks from Gyeongsang, Republic of Korea. A total of 3825 questing ticks were collected by the flagging method from 12 sites near animal farms in Gyeongsang from March to October 2021. A molecular genomic study was performed with ticks stored in 70% ethanol to detect Anaplasma genes by the previously described method. The monthly incidence of ticks varied by developmental stages, i.e., nymphs, adults, and larvae, and each of their populations peaked in May, March, and October, respectively. The predominant tick species were Haemaphysalis longicornis, Haemaphysalis sp., Haemaphysalis flava, Ixodes nipponensis, and Amblyomma testudinarium in order. To determine the Anaplasma infection rate, collected ticks were pooled into 395 groups. The minimum infection rate (MIR) of Anaplasma was 0.7% (27 pools). That of A. phagocytophilum was highest (23 pools, MIR 0.6%), followed by A. phagocytophilum-like Anaplasma spp. clade B (2 pools, MIR 0.1%), A. bovis (1 pool, MIR 0.1%), and A. capra (1 pool, MIR 0.1%), respectively. In this study, five species of ticks, including unidentified Haemaphysalis species, were collected in 12 survey sites in Gyeongsang, but their prevalence was somewhat different according to the tick species and survey sites. Further, the incidence rate (6.8%) of 4 Anaplasma spp. was not as high in tick pools. However, the results of this study may offer a basis for future epidemiological research and risk assessment of tick-borne diseases.

Sudden death caused by Aeromonas hydrophila in a Crab-eating Macaque (Macaca fascicularis) associated with captivity stress.

Aeromonas hydrophila is a facultative anaerobic gram-negative bacterium regarded as an opportunistic pathogen in animals. A 17-year-old female crab-eating macaque (Macaca fascicularis) died after experiencing anorexia and depression for several days. The carcass was severely emaciated, and the sternum was exposed under subcutaneous lesions in the thorax. Many abnormal pathological lesions were found, including tracheal inflammation, pulmonary inflammatory emphysema, yellowish discoloration of the liver, enlargement of the gall bladder, necrosis of the heart, congested bilateral kidneys, and enlargement of the adrenal glands. The stomach was empty, mucosal ulcerations were found, and the duodenum was congested. Giemsa staining revealed rod-shaped organisms in the whole blood smear and major organs, which were identified as A. hydrophila. The animal had experienced stress, and decreased immune system function possibly contributed to the infection.

A case of rickets in an artificially raised white-tailed eagle (Haliaeetus albicilla) chick at a zoo.

A two-week-old white-tailed eagle presented with an inability to stand and flex its limbs. Despite hatching naturally and owing to lack of parental attention, the bird was raised indoors by zookeepers with no access to sunlight. Palpation and radiographic examination of the bilateral tibiotarsus and femur bone revealed pronounced deformation and curvature, and bilateral decreased bone densities, respectively. The reduced calcium concentration in the blood was treated with calcium gluconate injections and calcium-supplemented feeds. Chopped mouse tails were fed directly, and whole pink-skinned nude mice were fed weekly. The zookeeper also gently massaged the bird and dressed it with a bandage. Sunlight exposure was provided daily. Saliva containing chicken feed was obtained from the mother. The bird could stand properly after four weeks of treatment, and the blood calcium concentration was restored to normal levels.

Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study.

PURPOSE: We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs). Materials and Methods: Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector-based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer. RESULTS: Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs. CONCLUSION: CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.

Successful repair of coracoid and femur fractures in a Eurasian eagle owl (Bubo bubo) and its post-release survival.

To our knowledge, this is the first case of concurrent diaphyseal left coracoid and left femoral fractures in a Eurasian eagle owl and its post-release survival in Korea. The femur was surgically repaired using an external skeletal fixator-intramedullary (IM) pin tie-in method, and the coracoid was repaired solely with an IM pin on day 6 after femur surgery. The eagle owl underwent a gradual rehabilitation process. The bird was successfully rehabilitated and released 101 d after initial presentation. The bird was monitored using a wildlife tracking device and was confirmed to have survived for over 5 mon in the wild.

First-line pembrolizumab versus dabrafenib/trametinib treatment for BRAF V600-mutant advanced melanoma.

BACKGROUND: Limited data are available to assist the selection between immune checkpoint inhibitors and BRAF/mitogen-activated protein kinase kinase inhibitors as first-line treatment for patients with BRAF-mutant advanced malignant melanoma. OBJECTIVE: To investigate the outcomes associated with first-line pembrolizumab or dabrafenib/trametinib treatment for advanced melanoma with activating BRAF V600 mutation. METHODS: Data of patients with BRAF V600-mutant melanoma who were treated with first-line pembrolizumab (n = 40) or dabrafenib/trametinib (n = 32) were analyzed. Tumor response, progression-free survival, and overall survival were evaluated. Immune evasion accompanied with emerging resistance to BRAF/mitogen-activated protein kinase kinase inhibitors was assessed. RESULTS: A longer overall survival was observed after first-line pembrolizumab treatment than after first-line dabrafenib/trametinib treatment (hazard ratio = 2.910, 95% CI: 1.552-5.459), although there were no significant differences in progression-free survival (P = .375) and response rate (P = .123). Emergence of resistance to dabrafenib/trametinib co-occurred with immune evasion, enabling melanoma cells to escape recognition and killing by Melan-A-specific CD8+ T cells. LIMITATIONS: Analysis was conducted in a retrospective manner. CONCLUSION: Pembrolizumab may be recommended over BRAF/mitogen-activated protein kinase kinase inhibitors as the first-line treatment in patients with advanced BRAF V600-mutant melanoma.