Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

Real-World Eligibility and Cost-Effectiveness Analysis of Empagliflozin for Heart Failure in Korea.

BACKGROUND: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. METHODS: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). RESULTS: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). CONCLUSION: There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01389843.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Synchronization of Intermittently Coupled Neural Networks With Coupling Delay.

In recent years, the synchronization of coupled neural networks (CNNs) has been extensively studied. However, existing results heavily rely on assuming continuous couplings, overlooking the prevalence of intermittent couplings in reality. In this article, we address for the first time the synchronization challenge posed by intermittently CNNs (ICNNs) with coupling delay. To overcome the difficulties arising from intermittent couplings, we put forward a general piecewise delay differential inequality to characterize the dynamics during both coupled intervals and decoupled intervals. Based on the proposed inequality, we establish delay-independent synchronization criteria (DISCs) for ICNNs, enabling them to tackle general coupling delay. Notably, unlike previous studies, the achievement of synchronization in our approach does not rely on external control. Furthermore, for ICNNs that synchronize only under small delays, we formulate non-linear matrix inequality (LMI)-based delay-dependent synchronization criteria (DDSCs) that are computationally efficient and do not require delay differentiability. Finally, we provide illustrative examples to demonstrate our theoretical results.

Improved switching condition for reachable set estimation of discrete-time switched delayed neural networks.

This research delves into the reachable set estimation (RSE) problem for general switched delayed neural networks (SDNNs) in the discrete-time context. Note that existing relevant research on SDNNs predominantly relies on either time-dependent or state-dependent switching approaches. The time-dependent versions necessitate the stability of each subnetwork beforehand, whereas the state-dependent switching strategies solely depend on the current state, thus disregarding the historical information of the neuron states. For fully harnessing the historical information pertaining to neuron states, a delicate combined switching strategy (CSS) is formulated with the explicit goal of furnishing a relaxed and less conservative design framework tailored for discrete-time SDNNs, where all subnetworks can also be unstable. By resorting to the established time-dependent multiple Lyapunov-Krasovskii functional (TDMLF) technique, the improved criteria are subsequently presented, ensuring that the reachable set encompassing all potential states of SDNNs is confined to an anticipated bounded set. Ultimately, the practicality and superiority of the presented RSE approach are thoroughly validated by two illustrative simulation examples.

Experiences of cancer survivors returning to work decision-making: a meta-synthesis of qualitative studies.

PURPOSE: Return to work for cancer survivors (CSs) may be challenging, and there is a research gap in integrating the relevant experiences of the return-to-work decision-making process for CSs. Our aim was to synthesize existing qualitative research that integrates the dynamic experiences of CSs in the return-to-work decision-making process and highlights the factors influencing the return-to-work decisions of CSs. METHODS: We retrieved qualitative studies on a relevant theme published in the PubMed, EBSCO, Scopus, Web of Science, Cochrane Library, and CINAHL databases since construction to December 2023. Literature screening, quality evaluation, and data analysis followed the PRISMA, Joanna Briggs Institute Critical Appraisal Tool (2016), and thematic analysis methods to ensure study reliability. The study was registered on PROSPERO (registration number: CRD42023429623). RESULTS: Ten articles were included, and six key outcomes were identified based on Social Cognitive Career Theory (SCCT) integration: points of concern for individuals, sense of self-efficacy, outcome expectations, work perception and belonging, medical advice and guidance, and effects of the external reactions. CONCLUSION: The decision-making process for CSs to return to work is affected by various personal and external factors. Effectively addressing personal appearance, financial, and emotional issues can enhance self-efficacy of CSs. Improving external perceptions of cancer patients and enhancing social support in the workplace and medical settings can help CSs make informed decisions regarding their return to work. IMPLICATIONS FOR CANCER SURVIVORS: The decision of CSs to return to work is a result of integrating personal, job, and medical care considerations. These findings contribute to the development of future interventions for CSs' return-to-work decisions that target an array of potential factors.

Clinical efficacy of endovascular revascularization combined with vacuum-assisted closure for the treatment of diabetic foot.

BACKGROUND: The diabetic foot is a common cause of disability and death, and comorbid foot infections usually lead to prolonged hospitalization, high healthcare costs, and a significant increase in amputation rates. And most diabetic foot trauma is complicated by lower extremity arteriopathy, which becomes an independent risk factor for major amputation in diabetic foot patients. AIM: To establish the efficacy and safety of endovascular revascularization (ER) combined with vacuum-assisted closure (VAC) for the treatment of diabetic foot. METHODS: Clinical data were collected from 40 patients with diabetic foot admitted to the Second Affiliated Hospital of Soochow University from April 2018 to April 2022. Diabetic foot lesions were graded according to Wagner's classification, and blood flow to the lower extremity was evaluated using the ankle-brachial index test and computerized tomography angiography of the lower extremity arteries. Continuous subcutaneous insulin infusion pumps were used to achieve glycemic control. Lower limb revascularization was facilitated by percutaneous tran-sluminal balloon angioplasty (BA) or stenting. Wounds were cleaned by nibbling debridement. Wound granulation tissue growth was induced by VAC, and wound repair was performed by skin grafting or skin flap transplantation. RESULTS: Of the 35 cases treated with lower limb revascularization, 34 were successful with a revascularization success rate of 97%. Of these, 6 cases underwent stenting after BA of the superficial femoral artery, and 1 received popliteal artery stent implantation. In the 25 cases treated with infrapopliteal artery revascularization, 39 arteries were reconstructed, 7 of which were treated by drug-coated BA and the remaining 32 with plain old BA. VAC was performed in 32 wounds. Twenty-four cases of skin grafting and 2 cases of skin flap transplantation were performed. Two patients underwent major amputations, whereas 17 had minor amputations, accounting for a success limb salvage rate of 95%. CONCLUSION: ER in combination with VAC is a safe and effective treatment for diabetic foot that can significantly improve limb salvage rates. The use of VAC after ER simplifies and facilitates wound repair.

Verapamil Enhances the Activity of Caspofungin against Cryptococcus neoformans Coincides with Inhibited Ca2+ /CN Pathway and Damage with Cell Wall Integrity.

Currently, the therapeutic effect on cryptococcal infection patients is hindered by toxicity and drug resistance, making it urgent to discover alternative antifungals. Calcium channel blockers, verapamil (VER), have shown effective antifungal effects in several fungi. Here, we found that VER has a significant antifungal effect on Cryptococcus neoformans (C. neoformans). Furthermore, VER has significant synergistic effects with multiple antifungals, even caspofungin (CAS). We confirmed that VER and CAS had a synergistic antifungal effect in the Galleria mellonella. We conducted in-depth research on the possible mechanism of the synergistic impact of VER and CAS. After treatment with VER, the chitosan content of C. neoformans ' cell wall decreased and in dopamine liquid culture medium, we observed the leakage of melanin. Through cell wall fluorescence staining and stress sensitivity analysis, we further demonstrated that VER impaired the integrity of the C. neoformans' cell wall. Another side, VER+CAS modification of C. neoformans membrane permeability, leading to intracellular ROS accumulation and mitochondrial membrane potential changes. VER eliminated the cytoplasmic calcium fluctuations caused by CAS stimulation and down-regulated the genes expression associated with the calcineurin pathway. In addition, we found that the enzyme activity of chitin deacetylase of C. neoformans is significantly influenced by the presence of Ca2+, suggesting that the use of VER may affect the activity. In summary, the synergistic antifungal effect of VER and CAS makes them effective and promising candidates for fungal treatment.

Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.

Alcohol consumption and the risk of all-cause and cause-specific mortality-a linear and nonlinear Mendelian randomization study.

BACKGROUND: Many observational studies support light-to-moderate alcohol intake as potentially protective against premature death. We used a genetic approach to evaluate the linear and nonlinear relationships between alcohol consumption and mortality from different underlying causes. METHODS: We used data from 278 093 white-British UK Biobank participants, aged 37-73 years at recruitment and with data on alcohol intake, genetic variants, and mortality. Habitual alcohol consumption was instrumented by 94 variants. Linear Mendelian randomization (MR) analyses were conducted using five complementary approaches, and nonlinear MR analyses by the doubly-ranked method. RESULTS: There were 20 834 deaths during the follow-up (median 12.6 years). In conventional analysis, the association between alcohol consumption and mortality outcomes was 'J-shaped'. In contrast, MR analyses supported a positive linear association with premature mortality, with no evidence for curvature (Pnonlinearity ≥ 0.21 for all outcomes). The odds ratio [OR] for each standard unit increase in alcohol intake was 1.27 (95% confidence interval [CI] 1.16-1.39) for all-cause mortality, 1.30 (95% CI 1.10-1.53) for cardiovascular disease, 1.20 (95% CI 1.08-1.33) for cancer, and 2.06 (95% CI 1.36-3.12) for digestive disease mortality. These results were consistent across pleiotropy-robust methods. There was no clear evidence for an association between alcohol consumption and mortality from respiratory diseases or COVID-19 (1.32, 95% CI 0.96-1.83 and 1.46, 95% CI 0.99-2.16, respectively; Pnonlinearity ≥ 0.21). CONCLUSION: Higher levels of genetically predicted alcohol consumption had a strong linear association with an increased risk of premature mortality with no evidence for any protective benefit at modest intake levels.

Genetic and brain similarity independently predict childhood anthropometrics and neighborhood socioeconomic conditions.

Linking the developing brain with individual differences in clinical and demographic traits is challenging due to the substantial interindividual heterogeneity of brain anatomy and organization. Here we employ an integrative approach that parses individual differences in both cortical thickness and common genetic variants, and assess their effects on a wide set of childhood traits. The approach uses a linear mixed model framework to obtain the unique effects of each type of similarity, as well as their covariance. We employ this approach in a sample of 7760 unrelated children in the ABCD cohort baseline sample (mean age 9.9, 46.8% female). In general, associations between cortical thickness similarity and traits were limited to anthropometrics such as height, weight, and birth weight, as well as a marker of neighborhood socioeconomic conditions. Common genetic variants explained significant proportions of variance across nearly all included outcomes, although estimates were somewhat lower than previous reports. No significant covariance of the effects of genetic and cortical thickness similarity was found. The present findings highlight the connection between anthropometrics as well as neighborhood socioeconomic conditions and the developing brain, which appear to be independent from individual differences in common genetic variants in this population-based sample.

Metformin treatment is associated with improved survival in diabetic patients hospitalized with acute heart failure: A prospective observational study using the Korean acute heart failure registry data.

AIMS: Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF. METHODS: The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m2 or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment. RESULTS: The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464-0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495-0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m2, P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40-49 %, or ≥50 %, P-for-interaction=0.224). CONCLUSIONS: Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Eligibility and Cost-Utility Analysis of Dapagliflozin in Patients with Heart Failure Across the Whole Spectrum of Ejection Fraction in South Korea.

BACKGROUND: The DAPA-HF and DELIVER trials demonstrated the clinical benefits of dapagliflozin in heart failure (HF) patients across the entire ejection fraction (EF) spectrum. However, further investigation is needed for the real-world application of dapagliflozin in HF patients. This study examines the proportion of real-world HF patients eligible for dapagliflozin and evaluates the cost-effectiveness of adding dapagliflozin to current HF therapy. METHODS: Data from the nationwide prospective registry, the Korean Acute Heart Failure (KorAHF) registry, were used to determine dapagliflozin eligibility based on the enrollment criteria of the DAPA-HF/DELIVER trials. A cost-utility analysis was conducted using a Markov model to assess the cost-effectiveness of dapagliflozin by comparing it to the standard of care. RESULTS: Out of 5178 KorAHF patients, 48.7% met the enrollment criteria of the DAPA-HF/DELIVER trials, while 89.5% met the label criteria (US Food and Drug Administration, European Medicines Agency, and Korean Ministry of Food and Drug Safety). Eligibility was highest among HF patients with preserved EF (55.3% vs. HF with mildly reduced EF and HF with reduced EF 46.4%). Dapagliflozin proved to be cost-effective, with an incremental cost-effectiveness ratio (ICER) of 4557 US dollar (US$) per quality-adjusted life year, which falls below the US$18,182 willingness-to-pay threshold. The cost-effectiveness benefit was more pronounced in patients with a left ventricular EF (LVEF) ≤ 40% (ICER US$3279 for LVEF ≤ 40% vs. US$8383 for LVEF > 40%). CONCLUSIONS: Discrepancies in dapagliflozin eligibility were observed between real-world data and clinical trial results. The addition of dapagliflozin to HF therapy proved to be highly cost-effective across the entire EF spectrum.

Risk of Nephritis and Recurrence in Kimura Disease: A Retrospective Study.

Background: Kimura disease (KD) presents a diagnostic challenge to clinicians because of its rarity and atypical symptoms in its early stages, and it is difficult to treat and prone to recurrence or involvement of other organs. Aims and Objectives: This study aims to investigate the possible relevance of renal involvement and recurrence by analysing the clinical presentations, laboratory results, histopathological features, therapeutic data and follow-up results of KD. Materials and Methods: A total of 27 patients diagnosed as KD in two hospitals from January 1999 to December 2021 were analysed retrospectively in this study based on the diagnosis of histopathology. Results: KD mainly affected male more than female (8:1) with the onset age ranging from 3 to 58 years (median 29.8 years). The common initial symptoms included subcutaneous soft tissue or lymph node enlargement, non-specific skin lesions and proteinuria. One patient presented cough and expectoration as the first symptoms. KD patients often had high levels of serum immunoglobulin E (IgE) and basophils, which exhibited a significantly positive correlation with renal involvement and recurrence (p < 0.05). Early mass resection could prevent the development of nephritis and decrease the risk of relapse (p < 0.05). Conclusion: KD should be noted in patients presenting with intractable and relapsing atopic skin lesions and (or) subcutaneous mass. Patients with high levels of serum IgE and blood basophils may be prone to developing KD-associated nephritis and predict a high risk of recurrence. Early surgical removal of the mass may result in a better prognosis.

Antifungal activity of the repurposed drug disulfiram against Cryptococcus neoformans.

Fungal infections have become clinically challenging owing to the emergence of drug resistance in invasive fungi and the rapid increase in the number of novel pathogens. The development of drug resistance further restricts the use of antifungal agents. Therefore, there is an urgent need to identify alternative treatments for Cryptococcus neoformans (C. neoformans). Disulfiram (DSF) has a good human safety profile and promising applications as an antiviral, antifungal, antiparasitic, and anticancer agent. However, the effect of DSF on Cryptococcus is yet to be thoroughly investigated. This study investigated the antifungal effects and the mechanism of action of DSF against C. neoformans to provide a new theoretical foundation for the treatment of Cryptococcal infections. In vitro studies demonstrated that DSF inhibited Cryptococcus growth at minimum inhibitory concentrations (MICs) ranging from 1.0 to 8.0 µg/mL. Combined antifungal effects have been observed for DSF with 5-fluorocytosine, amphotericin B, terbinafine, or ketoconazole. DSF exerts significant protective effects and synergistic effects combined with 5-FU for Galleria mellonella infected with C. neoformans. Mechanistic investigations showed that DSF dose-dependently inhibited melanin, urease, acetaldehyde dehydrogenase, capsule and biofilm viability of C. neoformans. Further studies indicated that DSF affected C. neoformans by interfering with multiple biological pathways, including replication, metabolism, membrane transport, and biological enzyme activity. Potentially essential targets of these pathways include acetaldehyde dehydrogenase, catalase, ATP-binding cassette transporter (ABC transporter), and iron-sulfur cluster transporter. These findings provide novel insights into the application of DSF and contribute to the understanding of its mechanisms of action in C. neoformans.

Development of the Telephone Triage Guidelines and Computerized Application for Symptom Management in Cancer Patients

Purpose@#This study aimed to develop standardized guidelines for telephone consultations and assess the impact of computerization on clinical utility. @*Methods@#Guidelines for patient classification were developed for 14 symptoms, validated by experts, and integrated into a real-time computer program. Patient classification involved categorizations of ‘observation,’ ‘outpatient,’ and ‘emergency’.Subsequent to computerization, a survey was conducted to evaluate its usefulness. @*Results@#Items with an Item-Content Validity Index (I-CVI) score of 0.75 or lower were removed or adjusted within the guidelines. Analysis of 200 consultation records indicated that lung cancer (87 cases) was the most common disease and the most prevalent symptom was pain (57 cases). Among 93 cases classified as ‘observation’, 6 patients visited the emergency room. Among 30 cases categorized as ‘outpatient’, 24 patients visited a clinic, and 6 patients visited the emergency room. Of the 19 cases classified as ‘emergency’, 18 patients actually visited the emergency room. User satisfaction from 12 nurses was very high, with an average score of 3.7/4. @*Conclusion@#Due to the standardized telephone triage and the concurrent implementation of a computerized program, healthcare professionals can conveniently and comprehensively analyze big data pertaining to patients’ symptoms. Ultimately, nurses were able to receive help with more specialized telenursing.

Phase 1/2a Study of Rivoceranib, a Selective VEGFR-2 Angiogenesis Inhibitor, in Patients with Advanced Solid Tumors / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to report the results from an early-phase study of rivoceranib, an oral tyrosine kinase inhibitor highly selective for vascular endothelial growth factor receptor 2, in patients with advanced solid tumors. @*Materials and Methods@#In this open-label, single-arm, dose-escalating, multicenter three-part phase 1/2a trial, patients had advanced solid tumors refractory to conventional therapy. Part 1 evaluated the safety and pharmacokinetics of five ascending once-daily doses of rivoceranib from 81 mg to 685 mg. Part 2 evaluated the safety and antitumor activity of once-daily rivoceranib 685 mg. Part 3 was conducted later, due to lack of maximum tolerated dose determination in part 1, to evaluate the safety and preliminary efficacy of once-daily rivoceranib 805 mg in patients with unresectable or advanced gastric cancer. @*Results@#A total of 61 patients were enrolled in parts 1 (n=25), 2 (n=30), and 3 (n=6). In parts 1 and 2, patients were white (45.5%) or Asian (54.5%), and 65.6% were male. The most common grade ≥ 3 adverse events were hypertension (32.7%), hyponatremia (10.9%), and hypophosphatemia (10.9%). The objective response rate (ORR) was 15.2%. In part 3, dose-limiting toxicities occurred in two out of six patients: grade 3 febrile neutropenia decreased appetite, and fatigue. The ORR was 33%. @*Conclusion@#The recommended phase 2 dose of rivoceranib was determined to be 685 mg once daily, which showed adequate efficacy with a manageable safety profile (NCT01497704 and NCT02711969).

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). @*Materials and Methods@#Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. @*Results@#RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). @*Conclusion@#GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.