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BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.
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OBJECTIVE: To investigate the incidence, characteristics, and outcomes of COVID-19 vaccine-related pericarditis (VRP) without myocarditis, we analyzed nationwide Korean data. PATIENTS AND METHODS: This is a retrospective nationwide report including all vaccinated Koreans with COVID-19 vaccine of any platform (BNT162b2, mRNA-1273, ChAdOx1, or Ad26.COV2.S) from February 26 to December 31, 2021. We analyzed the confirmed cases of COVID-19 VRP by the Expert Adjudication Committee. The incidence, clinical characteristics, and outcomes of COVID-19 VRP were analyzed. RESULTS: Among 44,322,068 Koreans with least one dose of COVID-19 vaccination, COVID-19 VRP was confirmed in 179 cases, with 1.73 per million shots (95% CI, 1.48 to 2.00 per million shots). The incidence of VRP was significantly higher in males than females (2.01 per 1 million doses vs 1.45 per 1 million doses, respectively; P=.029), in mRNA vaccines than in other vaccines (2.09 per 1 million doses vs 0.36 per 1 million doses, respectively; P<.001), and in those younger than 40 years of age than those older than 40 years of age (3.52 per 1 million doses vs 0.89 per 1 million doses, respectively; P<.001). The incidence of VRP was highest in males between the ages of 12 and 17 years (7.38 per 1 million doses; 95% CI, 2.01 to 16.07). Although there was no case of mortality, hemodynamically significant pericardial effusion requiring pericardial drainage was noted in 10 cases (5.6%). CONCLUSION: COVID-19 VRP was very rare and developed mainly in association with mRNA vaccines, especially in males younger than 40 years of age. The clinical course of VRP was excellent, and there were no cases of mortality. However, the development of hemodynamically significant pericardial effusion should be carefully monitored.
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The current memory system is facing obstacles to improvement, and ReRAM is considered a powerful alternative. All-inorganic α-CsPbI3 perovskite-based ReRAM working by electrochemical mechanism is reported, but the electrochemically active electrode raised difficulty in long-term stable operation, and bulk α-CsPbI3 device can not show resistive switching behavior with an inert metal top electrode. Herein, by making the α-CsPbI3 into QDs and applying it to the device with inert Au as the top electrode, the devices working by valence change mechanism are successfully fabricated. The large surface-to-volume ratio made an abundant amount of iodine vacancies and facile migration of vacancies allowed the device to work by valence change mechanism. The devices show reliable electrical characteristics, 800 cycles endurance and retention for over 4 × 104 s, and air stability for 1 month. This work demonstrates that applying the QDs can improve the stability and enable a new type of working mechanism in ReRAM.
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BACKGROUND: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies. METHOD: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring. RESULTS: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group (P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions (P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects. CONCLUSION: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).
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Afatinib , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Calidad de Vida , Humanos , Afatinib/uso terapéutico , Afatinib/efectos adversos , Afatinib/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Femenino , Persona de Mediana Edad , Receptores ErbB/genética , Anciano , Adulto , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologíaRESUMEN
Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología , Humanos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ratones Endogámicos C57BL , Femenino , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Línea Celular Tumoral , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Inmunoterapia/métodosRESUMEN
Intestinal microbiota and selected strains of commensal bacteria influence regulatory T (Treg) cell functionality in the colon. Nevertheless, whether and how microbiota changes the transcriptome profile and TCR specificities of colonic Tregs remain to be precisely defined. In this study, we have employed single-cell RNA sequencing and comparatively analyzed colonic Tregs from specific pathogen-free and germ-free (GF) mice. We found that microbiota shifts the activation trajectory of colonic Tregs toward a distinct phenotypic subset enriched in specific pathogen-free but not in GF mice. Moreover, microbiota induced the expansion of specific Treg clonotypes with shared transcriptional specificities. The microbiota-induced subset of colonic Tregs, identified as PD-1- CXCR3+ Tregs, displayed enhanced suppressive capabilities compared with colonic Tregs derived from GF mice, enhanced production of IL-10, and were the primary regulators of enteric inflammation in dextran sodium sulfate-induced colitis. These findings identify a hitherto unknown gut microbiota and immune cell interaction module that could contribute to the development of a therapeutic modality for intestinal inflammatory diseases.
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Maca (Lepidium meyenii Walp) is renowned for its phytochemicals, including amino acids, saponins, and macamides, confer nutritional and medicinal benefits. This study analyzed the bioactive constituents of maca via solid-state fermentation with Rhizopus oligosporus for 0-15 days. After fermentation, the l-carnitine content reached 157.3 µg/g. A 93% increase in macamide B was recorded after 7-day fermentation. Total flavonoid and saponin contents increased by 88.2% and 110.3%, respectively. The fermentation process significantly enhanced the physicochemical attributes of maca; in particular, its water retention and cholesterol-binding capacities increased by 1.73- and 4.30-fold, respectively, compared with the non-fermented maca. Moreover, fermented maca exhibited stronger antioxidant and α-glucosidase-inhibiting effects than non-fermented maca. Finally, the neuroprotective effect of maca on HT-22 cells increased by 23% after 5-day fermentation. These findings demonstrate the potential of fermented maca as a novel ingredient for foods, beverages, and pharmaceuticals. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01508-6.
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Micro-light-emitting diodes (µLEDs) have gained significant interest as an activation source for gas sensors owing to their advantages, including room temperature operation and low power consumption. However, despite these benefits, challenges still exist such as a limited range of detectable gases and slow response. In this study, we present a blue µLED-integrated light-activated gas sensor array based on SnO2 nanoparticles (NPs) that exhibit excellent sensitivity, tunable selectivity, and rapid detection with micro-watt level power consumption. The optimal power for µLED is observed at the highest gas response, supported by finite-difference time-domain simulation. Additionally, we first report the visible light-activated selective detection of reducing gases using noble metal-decorated SnO2 NPs. The noble metals induce catalytic interaction with reducing gases, clearly distinguishing NH3, H2, and C2H5OH. Real-time gas monitoring based on a fully hardware-implemented light-activated sensing array was demonstrated, opening up new avenues for advancements in light-activated electronic nose technologies.
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In this study, the corrosion behavior and degradation mechanism of Ti-Pt-coated stainless steel bipolar plates were investigated through electrochemical tests and surface analysis in a polymer electrolyte membrane water electrolysis (PEMWE) operating environment. The coated bipolar plate has a corrosion current density of only 1.68 × 10-8 A/cm2, which is an order of magnitude lower than that of the bare SS316L substrate (1.94 × 10-7 A/cm2), indicating that its corrosion resistance is superior to that of bare SS316L substrate. However, in the PEMWE operating environment, the protection efficiency of the coating and the corrosion resistance of the coated bipolar plate decreased. The degradation of the coated bipolar plate can be attributed to electrolyte penetration into the blistering areas of the coating layer with micro voids. Defects in the coating layer occur because of the pressure of oxygen gas generated within the coating layer under high-potential conditions, thereby exposing the substrate to the electrolyte and corrosion.
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This study investigates the molecular characteristics and therapeutic implications of the BRCA1 L1780P mutation, a rare variant prevalent among Korean hereditary breast cancer patients. Using patient-derived xenograft (PDX) models and cell lines (PDX-derived cell line) from carriers, sequencing analyses revealed loss of heterozygosity (LOH) at the BRCA1 locus, with one patient losing the wild-type allele and the other mutated allele. This reversion mutation may cf. resistance to homologous recombination deficiency (HRD)-targeting drugs such as PARP inhibitors (PARPi) and ATM inhibitors (ATMi). Although HRDetect and CHORD analyses confirmed a strong association between the L1780P mutation and HRD, effective initially, drug resistance developed in cases with reversion mutations. These findings underscore the complexity of using HRD prediction in personalized treatment strategies for breast cancer patients with BRCA1/2 mutations, as resistance may arise in reversion cases despite high HRD scores.
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Components of normal tissue architecture serve as barriers to tumor progression. Inflammatory and wound-healing programs are requisite features of solid tumorigenesis, wherein alterations to immune and non-immune stromal elements enable loss of homeostasis during tumor evolution. The precise mechanisms by which normal stromal cell states limit tissue plasticity and tumorigenesis, and which are lost during tumor progression, remain largely unknown. Here we show that healthy pancreatic mesenchyme expresses the paracrine signaling molecule KITL, also known as stem cell factor, and identify loss of stromal KITL during tumorigenesis as tumor-promoting. Genetic inhibition of mesenchymal KITL in the contexts of homeostasis, injury, and cancer together indicate a role for KITL signaling in maintenance of pancreas tissue architecture, such that loss of the stromal KITL pool increased tumor growth and reduced survival of tumor-bearing mice. Together, these findings implicate loss of mesenchymal KITL as a mechanism for establishing a tumor-permissive microenvironment.
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INTRODUCTION: Men with African ancestry have the highest incidence and mortality rates of prostate cancer (PCa) worldwide. METHODS: This study aimed to identify differentially methylated genes between tumor vs. adjacent normal and aggressive vs. indolent PCa in 121 African American patients. Epigenome-wide DNA methylation patterns in tumor DNA were assessed using the human Illumina Methylation EPIC V1 array. RESULTS: Around 5,139 differentially methylated CpG-sites (q < 0.01, lΔßl > 0.2) were identified when comparing normal vs. tumor, with an overall trend of hypermethylation in prostate tumors. Multiple representative differentially methylated regions (DMRs), including immune-related genes, such as CD40, Galectin3, OX40L, and STING, were detected in prostate tumors when compared to adjacent normal tissues. Based on an epigenetic clock model, we observed that tumors' total number of stem cell divisions and the stem cell division rate were significantly higher than adjacent normal tissues. Regarding PCa aggressiveness, 2,061 differentially methylated CpG-sites (q < 0.05, lΔßl > .05) were identified when the grade group (GG)1 was compared with GG4/5. Among these 2,061 CpG sites, 155 probes were consistently significant in more than one comparison. Among these genes, several immune system genes, such as COL18A1, S100A2, ITGA4, HLA-C, and ADCYAP1, have previously been linked to tumor progression in PCa. CONCLUSION: Several differentially methylated genes involved in immune-oncologic pathways associated with disease risk or aggressiveness were identified. In addition, 261 African American-specific differentially methylated genes related to the risk of PCa were identified. These results can shedlight on potential mechanisms contributing to PCa disparities in the African American Population.
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Negro o Afroamericano , Metilación de ADN , Estudio de Asociación del Genoma Completo , Neoplasias de la Próstata , Humanos , Masculino , Negro o Afroamericano/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/etnología , Persona de Mediana Edad , Anciano , Epigenoma , Islas de CpG , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genéticaRESUMEN
Numerous studies on neuromorphic computing systems and their associated synaptic devices have been reported for the efficient processing of complex data. Among them, organic electrochemical transistors (OECTs) have attracted considerable attention owing to their advantages such as low cost, high scalability, and facile electrical modulation. However, the requirement of supplementary processing for ionic transport control to actualize or enhance synaptic attributes necessitates a compromise between their inherent benefits. Here, we developed a simple method, photoinduced crosslinking, which can control the structure of conjugated polymers in OECTs to improve ionic transport control. Crosslinked polymers increase the ion doping efficiency and allow sequential anion movements, which leads to high linearity in OECTs. The fabricated device also exhibited enhanced synaptic properties such as a long retention time, wide dynamic range, and high recognition accuracy. This innovative approach opens up new possibilities for the construction of next-generation artificial synapses.
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PURPOSE: To explore the predictive potential of serial computed tomography (CT) radiology reports for pancreatic cancer survival using natural language processing (NLP). METHODS: Deep-transfer-learning-based NLP models were retrospectively trained and tested with serial, free-text CT reports, and survival information of consecutive patients diagnosed with pancreatic cancer in a Korean tertiary hospital was extracted. Randomly selected patients with pancreatic cancer and their serial CT reports from an independent tertiary hospital in the United States were included in the external testing data set. The concordance index (c-index) of predicted survival and actual survival, and area under the receiver operating characteristic curve (AUROC) for predicting 1-year survival were calculated. RESULTS: Between January 2004 and June 2021, 2,677 patients with 12,255 CT reports and 670 patients with 3,058 CT reports were allocated to training and internal testing data sets, respectively. ClinicalBERT (Bidirectional Encoder Representations from Transformers) model trained on the single, first CT reports showed a c-index of 0.653 and AUROC of 0.722 in predicting the overall survival of patients with pancreatic cancer. ClinicalBERT trained on up to 15 consecutive reports from the initial report showed an improved c-index of 0.811 and AUROC of 0.911. On the external testing set with 273 patients with 1,947 CT reports, the AUROC was 0.888, indicating the generalizability of our model. Further analyses showed our model's contextual interpretation beyond specific phrases. CONCLUSION: Deep-transfer-learning-based NLP model of serial CT reports can predict the survival of patients with pancreatic cancer. Clinical decisions can be supported by the developed model, with survival information extracted solely from serial radiology reports.
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Aprendizaje Profundo , Procesamiento de Lenguaje Natural , Neoplasias Pancreáticas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Pronóstico , Curva ROCRESUMEN
OBJECTIVE: The objective of this study was to investigate the longitudinal changes in cranial growth following fronto-orbital advancement (FOA) surgery in patients with unilateral and bilateral coronal craniosynostosis. METHODS: This retrospective review analyzed head circumference (HC) and CT data during preoperative (T0), immediate postoperative (T1), and final follow-up (T2) visits in 40 patients (23 female, 17 male) who underwent FOA using either the open approach or distraction osteogenesis (DO) between 1987 and 2018. The mean follow-up period was 90.62 months. The z-scores of HC, CT-based intracranial volume, anteroposterior diameter (APD), biparietal diameter (BPD), and cranial height (CH) were calculated using sex- and age-specific standards. Logistic regression analysis was performed. RESULTS: While the z-scores of HC, intracranial volume, and BPD remained within the normal range, the z-scores of APD fluctuated between -2 and -1, and the z-scores of CH were > 2, indicating a substantial elevation compared with norms from T0 to T2. Age at surgery significantly influenced the z-scores of HC, BPD, and CH at T2 (all p < 0.05). Delayed surgical timing was correlated with increased BPD and CH z-scores from T1 to T2 (p = 0.007 and 0.019, respectively). The DO for FOA resulted in elevated HC z-scores at T2 and increased APD from T0 to T1, followed by a significant APD relapse from T1 to T2. CONCLUSIONS: These findings suggest that delayed surgical timing may support better cranial growth, as indicated by increased HC at long-term follow-up. However, delayed timing is also associated with worsening abnormally elevated CH. Despite the immediate APD expansion and long-term HC increase with DO, potential relapse warrants caution. While intentional overcorrection of APD is recommended, careful consideration of surgical timing and planning is essential.
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Background: In v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant colorectal cancer (CRC), encorafenib-cetuximab has been established as standard second-line therapy, but not all patients respond and the duration of response is relatively short. Overcoming intrinsic or acquired resistance to BRAF/EGFR inhibitors is crucial for enhancing treatment outcomes in metastatic BRAF-mutated CRC. The aim of the study is to investigate the resistance mechanisms in BRAF-mutant CRC patient refractory to BRAF/EGFR targeted therapy. Methods: We established patient-derived cells (PDCs) from a patient with BRAF/PTEN-mutant metastatic colon cancer who progressed rapidly on encorafenib plus cetuximab. To explore potential treatment options for inherent resistance caused by simultaneous PTEN mutation in BRAF-mutated CRC, we conducted cell viability assays using PDCs treated with encorafenib-cetuximab in combination with a cyclin-dependent kinase-4 and 6 (CDK4/6) inhibitor. Results: The patient's tumor had concurrent PTEN loss-of-function alteration at diagnosis and PDCs were generated from ascites after resistance to the BRAF/EGFR inhibitor. The PDCs were resistant to the encorafenib-cetuximab combination even at a high concentration of cetuximab (up to 500 µg/mL). Adding the CDK4/6 inhibitor, ribociclib, to encorafenib-cetuximab showed a synergistic effect in a proliferation assay. Ribociclib plus encorafenib-cetuximab represented a significantly lower expression of Ki-67 compared to the dual combination alone. An MTS assay showed that triplet therapy with ribociclib, encorafenib, and cetuximab suppressed cell viability more efficiently than the two-drug combinations. Investigating the combined effect of triplet therapy using the calculated combination index (CI) showed that ribociclib had a synergistic effect with encorafenib-cetuximab when applied to PDCs with a concurrent BRAF/PTEN mutation. Conclusions: Our results suggest that combining the CDK4/6 inhibitor with the BRAF/EGFR inhibitor might be a novel treatment strategy for concomitant BRAF and PTEN-mutant CRC.
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BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5â¯%) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2â¯% (27/1350) of patients with colorectal cancer, followed by 3.48â¯% (32/920) of patients with gastric cancer and 3.88â¯% (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3â¯% (27/99) had a concomitant KRAS mutation. More than 50â¯% of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1â¯% (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9â¯%, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5â¯%) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.
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Amplificación de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Proteínas Proto-Oncogénicas p21(ras)/genética , Femenino , Masculino , Persona de Mediana Edad , Anciano , Neoplasias/genética , Neoplasias/patología , Adulto , Prevalencia , Biomarcadores de Tumor/genética , Metástasis de la Neoplasia/genéticaRESUMEN
Background: Anterior combined latissimus dorsi and teres major (aLDTM) tendon transfer has shown promise as a treatment for anterior superior irreparable rotator cuff tears (ASIRCTs). Our study aimed to compare aLDTM clinical outcomes for ASIRCTs between young and elderly patients. Methods: This retrospective study reviewed data from patients who underwent aLDTM tendon transfer for ASIRCTs. Exclusion criteria were unavailability for assessment, <2-year follow-up, or loss to follow-up. Clinical evaluations included visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), active range of motion (aROM), strength, and complications. Radiologic assessments included acromiohumeral distance, Hamada classification, and integrity of transferred tendon. Patients were divided into group total (all ages), group old (≥70 years), and group young (≤60 years). Results: A total of 123 patients were enrolled with 39 in group young (mean age, 56.6±4.9 years) and 27 in group old (mean age, 73.6±2.3 years). Postoperatively, both groups showed significant improvements in VAS, ASES, and SANE scores and improved aROM for forward elevation, abduction, and internal rotation. No significant differences were noted between the groups. Strength increment was not significantly different between the groups. In comparison to the total cohort, both group young and group old demonstrated comparable results in VAS, ASES, and SANE scores and in aROM and radiological assessments. Furthermore, similar rates of complications, including re-tears and postoperative infections, were observed across all three groups. Conclusions: Our study highlights the effectiveness of aLDTM transfer for ASIRCTs with minimal glenohumeral arthritis, demonstrating similar outcomes in both Group Young and group old patients. Moreover, patients in these distinct age groups showed comparable clinical results when compared to Group Total. Level of evidence: III.