Microsecond Electrical Breakdown in Water: Advances Using Emission Analysis and Cavitation Bubble Theory.

Electrical discharges in water are a subject of major interest because of both the wide range of potential applications and the complexity of the processes. This paper aimed to provide significant insights to better understand processes involved during a microsecond electrical discharge in water, especially during the propagation and the breakdown phases. Two different approaches were considered. The first analysis focused on the emission produced by the discharge during the propagation using fast imaging measurements and spatially resolved optical emission spectroscopy. The excited species H, O, and OH were monitored in the whole interelectrode gap. The second analysis concerned the thermodynamic conditions induced by the breakdown of the discharge. The time evolution of the bubble radius was simulated and estimation of the initial pressure of the cavitation bubble was performed using the Rayleigh-Plesset model. Values of about 1.7 × 107 Pa and 1.2 × 108 Pa were reported for the cathode and anode regimes, respectively. This multidisciplinary approach constitutes a new step to obtain an accurate physical and chemical description of pin-to-pin electrical discharges in water.

Post K-Pg diversification of the mammalian order Eulipotyphla as suggested by phylogenomic analyses of ultra-conserved elements.

The origin of the mammalian order Eulipotyphla has been debated intensively with arguments around whether they began diversifying before or after the Cretaceous-Palaeogene (K-Pg) boundary at 66 Ma. Here, we used an in-solution nucleotide capture method and next generation DNA sequencing to determine the sequence of hundreds of ultra-conserved elements (UCEs), and conducted phylogenomic and molecular dating analyses for the four extant eulipotyphlan lineages-Erinaceidae, Solenodontidae, Soricidae, and Talpidae. Concatenated maximum-likelihood analyses with single or partitioned models and a coalescent species-tree analysis showed that divergences among the four major eulipotyphlan lineages occurred within a short period of evolutionary time, but did not resolve the interrelationships among them. Alternative suboptimal phylogenetic hypotheses received consistently the same amount of support from different UCE loci, and were not significantly different from the maximum likelihood tree topology, suggesting the prevalence of stochastic lineage sorting. Molecular dating analyses that incorporated among-lineage evolutionary rate differences supported a scenario where the four eulipotyphlan families diversified between 57.8 and 63.2 Ma. Given short branch lengths with low support values, traces of rampant genome-wide stochastic lineage sorting, and post K-Pg diversification, we concluded that the crown eulipotyphlan lineages arose through a rapid diversification after the K-Pg boundary when novel niches were created by the mass extinction of species.

High Conductivity and Surface Area of Mesoporous Ti0.7W0.3O2 Materials as Promising Catalyst Support for Pt in Proton-Exchange Membrane Fuel Cells.

In this work, mesoporous Ti0.7W0.3O2 materials with high conductivity and surface area as promising catalyst support for Pt in Proton-Exchange Membrane Fuel Cells (PEMFCs) were synthesized via a single-step solvothermal process at low-temperature without using any surfactants or stabilizers. The characterizations of material are measured via XRD, TEM, SEM-EDS, and BET as well as electronic conductivity measurement. As a result, Ti0.7W0.3O2 formed a homogenous solid solution with mesoporous anatase-TiO2 structure and uniformly spherical nanoparticles morphology of about ~10 nm diameter, together with a high electrical conductivity of 0.022 S/cm compared to that of undoped-TiO2 (1.37×10-7 S/cm), which implied that tungsten (VI) ions was successfully doped into anatase-TiO2 lattices. The N2 adsorption/desorption isotherms indicated that Ti0.7W0.3O2 is being mesoporous structure with high surface area up to ~202 m²/g, which is nearly similar to that of the commercial Vulcan XC72 (~232 m²/g). The Pt nanoparticles was easily anchored onto Ti0.7W0.3O2 surface by the chemical reduction process using NaBH4 as a reducing agent. The spherical Pt nanoparticles of ~9 nm in diameter were deposited uniformly on the mesoporous support. These results suggested that mesoporous Ti0.7W0.3O2 materials synthesized are promising catalyst supports to replace carbon-based supports for Proton-exchange membrane fuel cells.

Clinical outcomes after discontinuing anticoagulant therapy in patients with first unprovoked venous thromboembolism.

BACKGROUND: The duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) should balance the likelihood of VTE recurrence against the risk of major bleeding. OBJECTIVES: Analyze rates and case-fatality rates (CFRs) of recurrent VTE and major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE after at least 3 months of anticoagulation. METHODS: We compared the rates and CFRs in patients of the Registro Informatizado Enfermedad Trombo Embólica (RIETE) and Contemporary management and outcomes in patients with venous thromboembolism registries. We used logistic regression models to identify predictors for recurrent pulmonary embolism (PE) and major bleeding. RESULTS: Of 8261 patients with unprovoked VTE in RIETE registry, 4012 (48.6%) had isolated deep vein thrombosis (DVT) and 4250 had PE. Follow-up (median, 318 days) showed 543 recurrent DVTs, 540 recurrent PEs, 71 major bleeding episodes, and 447 deaths. The Contemporary management and outcomes in patients with venous thromboembolism registry yielded similar results. Corresponding CFRs of recurrent DVT, PE, and major bleeding were 0.4%, 4.6%, and 24%, respectively. On multivariable analyses, initial PE presentation (hazard ratio [HR], 3.03; 95% CI, 2.49-3.69), dementia (HR, 1.47; 95% CI, 1.01-2.13), and anemia (HR, 0.72; 95% CI, 0.57-0.91) predicted recurrent PE, whereas older age (HR, 2.11; 95% CI, 1.15-3.87), inflammatory bowel disease (HR, 4.39; 95% CI, 1.00-19.3), and anemia (HR, 2.24; 95% CI, 1.35-3.73) predicted major bleeding. Prognostic scores were formulated, with C statistics of 0.63 for recurrent PE and 0.69 for major bleeding. CONCLUSION: Recurrent DVT and PE were frequent but had low CFRs (0.4% and 4.6%, respectively) after discontinuing anticoagulation. On the contrary, major bleeding was rare but had high CFR (24%). A few clinical factors may predict these outcomes.

Results of acute cerebral infarction treatment with hyperbaric oxygen therapy, 2020-2022.

BACKGROUND: Cerebral stroke is the third leading cause of death after cardiovascular disease, cancer and the leading cause of disability for patients. Hyperbaric oxygen is a non-drug treatment that has the potential to improve brain function for patients with ischaemic stroke. The objective of this study was to evaluate the results of treatment of acute cerebral infarction with hyperbaric oxygen therapy (HBOT). MATERIALS AND METHODS: This was a case-control study. One hundred ninety-five patients diagnosed with cerebral infarction, with signs of onset within 24 hours, were treated at the Centre for Underwater Medicine and Hyperbaric Oxygen of Vietnam National Institute of Maritime Medicine during the period from January 2020 to December 2022. Study group included 100 patients with acute cerebral infarction treated with a combination of HBOT and medication and reference group included 95 patients treated by medication only (antiplatelets drugs, statins, control of associated risks factors) RESULTS: After 7 days of treatment with hyperbaric oxygen (HBO), symptoms such as headache, dizziness, nausea, sensory disturbances, and Glasgow score of the study group improved better than that of the reference group (p < 0.01). Movement recovery in the study group was better than the reference group: the percentage of patients with mild and moderate paralysis in the study group increased higher than that of the reference group (86.0% and 68.4%), the degree of complete paralysis of the study group decreased more than that of the reference group (14.0% and 31.6%). The degree of independence in daily activities in the study group was better than the reference group. In the study group, the percentage of patients with complete independence in daily life increased from 27.0% to 84.0%. In the reference group, the rate of patients who were independent in their daily activities increased from 37.9% to 51.6%. The average number of treatment days of the study group was 10.32 ± 2.41 days and it the reference group 14.51 ± 3.24 days. CONCLUSIONS: Hyperbaric oxygen therapy is a non-drug treatment with many good effects in the treatment of cerebral infarction, especially acute cerebral infarction. HBOT reduces and improves functional symptoms, improves mobility, and reduces treatment time for patients.

The Diagnostic Power of Circulating miR-1246 in Screening Cancer: An Updated Meta-analysis.

Background: MicroRNA-1246 (miR-1246), an oncomiR that regulates the expression of multiple cancer-related genes, has been attracted and studied as a promising indicator of various tumors. However, diverse conclusions on diagnostic accuracy have been shown due to the small sample size and limited studies included. This meta-analysis is aimed at systematically assessing the performance of extracellular circulating miR-1246 in screening common cancers. Methods: We searched the PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases for relevant studies until November 28, 2022. Then, the summary receiver operating characteristic (SROC) curves were drawn and calculated area under the curve (AUC), diagnostic odds ratio (DOR), sensitivity, and specificity values of circulating miR-1246 in the cancer surveillance. Results: After selection and quality assessment, 29 eligible studies with 5914 samples (3232 cases and 2682 controls) enrolled in the final analysis. The pooled AUC, DOR, sensitivity, and specificity of circulating miR-1246 in screening cancers were 0.885 (95% confidence interval (CI): 0.827-0.892), 27.7 (95% CI: 17.1-45.0), 84.2% (95% CI: 79.4-88.1), and 85.3% (95% CI: 80.5-89.2), respectively. Among cancer types, superior performance was noted for breast cancer (AUC = 0.950, DOR = 98.5) compared to colorectal cancer (AUC = 0.905, DOR = 47.6), esophageal squamous cell carcinoma (AUC = 0.757, DOR = 8.0), hepatocellular carcinoma (AUC = 0.872, DOR = 18.6), pancreatic cancer (AUC = 0.767, DOR = 12.3), and others (AUC = 0.887, DOR = 27.5, P = 0.007). No significant publication bias in DOR was observed in the meta-analysis (funnel plot asymmetry test with P = 0.652; skewness value = 0.672, P = 0.071). Conclusion: Extracellular circulating miR-1246 may serve as a reliable biomarker with good sensitivity and specificity in screening cancers, especially breast cancer.

A retrospective study of endogenous endophthalmitis-related pyogenic liver abscess: An increasing complication in North Vietnam.

Introduction: Endogenous endophthalmitis-related Klebsiella pyogenic liver abscess is a rare complication of metastatic infection. In most cases, visual acuity results are often impaired, even blind, and even with aggressive treatment with topical antibiotics, the final results are unsatisfactory. The objective of this study is to retrospectively based on medical records to describe clinical features, risk factors, and visual outcomes of patients with endogenous endophthalmitis-related pyogenic liver abscesses. Methods: We reported a case series of 12 endogenous endophthalmitis-related pyogenic liver abscess patients from March 2021 to 2023. All cases of endogenous endophthalmitis were diagnosed at admission or during the hospital stay. Results: From the medical records of 588 pyogenic liver abscess patients, we found 12 cases of endogenous endophthalmitis with 2.0%. The result showed a mean age of 61.5 ± 12.0 (41-78), diabetes mellitus (7 of 12), right lobe (7 of 12), single abscess (9 of 12), and the mean largest abscess diameter of 5.8 ± 1.7 cm (3.3-9). All patients had ocular symptoms such as eye pain (9 of 12), pus discharge (3 of 12), hypopyon (1 of 12), swollen eyelids (2 of 12), and corneal edema (2 of 12), pyogenic liver abscess before endogenous endophthalmitis (10 of 12), the median interval between endogenous endophthalmitis and pyogenic liver abscess 6.1 ± 1.9 days, ocular symptoms before diagnosis endogenous endophthalmitis 4.4 ± 2.3 days. All affected eyes were injected intravitreously with ceftazidime, amikacin, and vancomycin. Two patients underwent evisceration. Conclusions: Endogenous endophthalmitis has permanent morbidity, reducing visual acuity, poor quality of life, and lacks the warning signs, so it is essential for early detection of symptoms and referral to ophthalmologists.

The diagnostic performance of AFP and PIVKA-II models for non-B non-C hepatocellular carcinoma.

OBJECTIVE: This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC). RESULTS: A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.

Insights into the effects of synthesis techniques and crosslinking agents on the characteristics of cellulosic aerogels from Water Hyacinth.

Aerogel cellulose materials were synthesised from Water hyacinth and different crosslinkers, such as kymene and a mixture of polyvinyl alcohol (PVA) and glutaraldehyde (GA). The effects of using a magnetic stirrer and ultrasonic methods were investigated. The results show that materials prepared using ultrasonic methods have higher porosity and lower density. The thermal conductivity of the synthesised aerogel cellulose could be as low as 0.0281 W m K-1, showing the good heat insulation performance of this material. Absorption capacity was tested using diesel oil (DO), and the highest capacities of 58.82 and 52.03 g g-1 of DO were found with kymene and PVA + GA as crosslinkers, respectively. The reusability of the materials was tested. After 10 cycles, the DO absorption capacity was 62.8% of the value of the first cycle for the aerogel cellulose sample with kymene as the crosslinker and 72.7% for the sample with PVA + GA as the crosslinking agent.

Valorization of agriculture waste biomass as biochar: As first-rate biosorbent for remediation of contaminated soil.

Each year, Asia produces an estimated 350 million tonnes of agricultural residues. According to Ministry of Power projections, numerous tonnes of such waste are discarded each year, in addition to being used as green manure. The methodology used to convert agricultural waste into the most valuable biochar, as well as its critical physical and chemical properties, were described in this review. This review also investigates the beneficial effects of bio and phytoremediation on metal(lloid)-contaminated soil. Agriculture biomass-based biochar is an intriguing organic residue material with the potential to be used as a responsible solution for metal(lloid) polluted soil remediation and soil improvement. Plants with faster growth and higher biomass can meet massive remediation demands. Recent research shows significant progress in agricultural biomass-based biomass conversion as biochar, as well as understanding the frameworks of metal(lloid) accumulation and mobility in plants used for metal(lloid) polluted soil remediation. Biochar made from various agricultural biomass can promote native plant growth and improve phytoremediation efficiency in polluted soil with metal(lloid)s. This carbon-enriched biochar promotes native microbial activity by neutralising pH and providing adequate nutrition. Thus, this review critically examines the feasibility of converting agricultural waste biomass into biochar, as well as the impact on plant and microbe remediation potential in metal(lloid)s polluted soil.

EGFR-plasma mutations in prognosis for non-small cell lung cancer treated with EGFR TKIs: A meta-analysis.

BACKGROUND: The plasma-based epidermal growth factor receptor (EGFR) mutation testing is approved recently to use in clinical practice. However, it has not been used as a prognostic marker yet because of contradictory results. AIM: This meta-analysis aims to clarify the role of the EGFR-plasma test in prognosis for non-small cell lung cancer (NSCLC) who have mutant tumors and receive EGFR tyrosine kinase inhibitors (TKIs). METHODS AND RESULTS: The PubMed/MEDLINE, Web of Science, Cochrane Library, and Google Scholar databases were searched for relevant studies by April 10, 2021. The hazard ratio (HR) from reports was extracted and used to assess the correlation of EGFR-plasma status with progression-free survival (PFS) and overall survival (OS). A total of 35 eligible studies with 4106 patients were enrolled in the final analysis. Patients with concurrent EGFR mutations in pretreatment plasma have shorter PFS (HR = 2.00, 95% confidence interval [CI]: 1.73-2.31, p < .001) and OS time (HR = 2.31, 95% CI: 1.89-2.83, p < .001) compared to the tumor-only mutation cases. Besides, the persistence of EGFR-activating mutations in post-treatment plasma is associated with worse PFS (HR = 3.84, 95% CI: 2.96-4.99, p < .001) and OS outcome (HR = 3.22, 95% CI: 2.35-4.42, p < .001) compared to others. Notably, the prognostic value of the EGFR-plasma test is also validated in treatment with third-generation EGFR TKI and significance regardless of different detection methods. CONCLUSION: The presence of EGFR-plasma mutations at pretreatment and after EGFR TKI initiation is the worse prognostic factor for PFS and OS in NSCLC.

Synthesis, Characteristics, Oil Adsorption, and Thermal Insulation Performance of Cellulosic Aerogel Derived from Water Hyacinth.

Cellulosic aerogel from water hyacinth (WH) was synthesized to address the dual environmental issues of water hyacinth pollution and the production of a green material. Raw WH was treated with sodium hydroxide (NaOH) with microwave assistance and in combination with hydrogen peroxide (H2O2). The results from X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM) showed that lignin and hemicellulose were markedly decreased after treatment, reducing from 24.02% hemicellulose and 5.67% lignin in raw WH to 8.32 and 1.92%, respectively. Cellulose aerogel from the pretreated WH had a high porosity of 98.8% with a density of 0.0162 g·cm-3 and a low thermal conductivity of 0.030 W·m-1·K-1. After modification with methyl trimethoxysilane (MTMS) to produce a highly hydrophobic material, WH aerogel exhibited high stability for oil absorption at a capacity of 43.3, 43.15, 40.40, and 41.88 (g·g-1) with diesel oil (DO), motor oil (MO), and their mixture with water (DO + W and MO + W), respectively. The adsorption remained stable after 10 cycles.

The diagnostic power of CD117, CD13, CD56, CD64, and MPO in rapid screening acute promyelocytic leukemia.

OBJECTIVE: The same immuno-phenotype between HLA-DR-negative acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) causes APL rapid screening to become difficult. This study aimed to identify the associated antigens for APL and the best model in clinical uses. RESULTS: A total of 36 APL (PML-RARA+) and 29 HLA-DR-negative non-APL patients enrolled in this study. When a cut-off point of 20% events was applied to define positive or negative status, APL and non-APL patients share a similar immuno-phenotype of CD117, CD34, CD11b, CD13, CD33, and MPO (P > 0.05). However, expression intensity of CD117 (P = 0.002), CD13 (P < 0.001), CD35 (P < 0.001), CD64 (P < 0.001), and MPO (P < 0.001) in APL are significantly higher while CD56 (P = 0.049) is lower than in non-APL subjects. The Bayesian Model Averaging (BMA) analysis identified CD117 (≥ 49% events), CD13 (≥ 88% events), CD56 (≤ 25% events), CD64 (≥ 42% events), and MPO (≥ 97% events) antigens as an optimal model for APL diagnosis. A combination of these factors resulted in an area under curve (AUC) value of 0.98 together with 91.7% sensitivity and 93.1% specificity, which is better than individual markers (AUC were 0.76, 0.84, 0.65, 0.82, and 0.85, respectively) (P = 0.001).

Smoking habit and chemo-radiotherapy and/or surgery affect the sensitivity of EGFR plasma test in non-small cell lung cancer.

OBJECTIVE: This study aimed to identify the influential factors for the sensitivity of epidermal growth factor receptor (EGFR) plasma test in non-small cell lung cancer (NSCLC). The mutations were detected in tumor tissue and matched plasma samples from 125 newly diagnosed adenocarcinoma, clinical-stage IIIB-IV patients, and compared the diagnostic values of EGFR plasma test between groups of clinical characteristics. The influential factors for the sensitivity were identified and assessed by logistic regression. RESULTS: EGFR mutations were detected in 65 (52.0%) tumor tissue and 50 (40.0%) matched plasma samples (P = 0.028). Compared to the tissue method, the concordance rate, sensitivity, and specificity of the EGFR plasma test were 86.4%, 75.4%, and 98.3%, respectively. Notably, we found that sensitivity of the test is higher in non-smokers (84.1%) compared to smokers (57.1%, P = 0.018), and in treatment naïve subjects (85.7%) compared to whom undergone chemo-radiotherapy with/without surgery before testing (56.5%, P = 0.009). Furthermore, the highest sensitivity was attained in patients without these two factors (90.3%), whilst the lowest value was noted in those with both factors (40.0%, P = 0.004). The multivariable analysis confirmed that smoking habit and treatment history have independently negative impacts on sensitivity (OR = 0.24, P = 0.019, and OR = 0.36, P = 0.047, respectively).

Cellulose-based aerogels from sugarcane bagasse for oil spill-cleaning and heat insulation applications.

A promising and economic material for various applications, such as thermal insulation in construction building and oil clean-up in marine ecosystems, is successfully developed from the by-product of the sugarcane industry. Biodegradable sugarcane bagasse aerogels are produced using polyvinyl alcohol (PVA) binder, followed by a freeze-drying method. This environmental-friendly recycled aerogel has an ultra-low density ([0.016-0.112] g/cm3), a high porosity ([91.9-98.9]%), and a very low thermal conductivity ([0.031-0.042] W/mK). Its superhydrophobicity properties and its maximum oil absorption capacity (up to 25 g/g) are measured after coating aerogel samples with methyltrimethoxysilane (MTMS). The biodegradable aerogel has a Young's modulus of 88 K Pa and can be bent without breaking, demonstrating its high flexibility.

Three-dimensional CT observation of position and movability of the scapula in the horse using carcasses of Falabella.

The three-dimensionally real position and movement of the scapula in the lateral side of the ribcage could not be clarified in the horse, since the body size of the horse is too large to apply the CT scanning and image analysis methods. In this study, therefore, we examined the position and the movability of scapula using a carcass of the Falabella which is one of the smallest breeds of the horse. The whole skeletal system in thoracic part of the Falabella could be three-dimensionally observed by CT scanning method. The three-dimensional images show that the scapula cranially slides and the ventral part of the scapula dorso-cranially rotates, when the shoulder joint moves to the most cranial position as simulation. The three-dimensional rotation angle was approximately 10 degrees. As a result of comparative osteology of the scapula between Falabella and the large draft horse, the infraspinous fossa was caudally enlarged in the larger draft horse, whereas the Falabella had narrower infraspinous fossa. We suggest that it may be due to the adaptational morphological change in the scapula bearing various body weights among breeds. The three-dimensional CT image analysis and the simulation in carcass contribute to the analysis of the bone movements of the horse during walking and running locomotion as well as the motion analysis from external functional-morphological data.

Emergence role of nucleated red blood cells in molecular response evaluation for chronic myeloid leukemia.

PURPOSE: To investigate and evaluate the role of nucleated red blood cells (NRBCs) and other markers in predicting remission failure in chronic myeloid leukemia (CML) patients treated with imatinib. METHODS: Seventy-one CML patients with BCR-ABL(+) in bone marrow cells were selected for this study. Molecular response evaluations were done every three months according to the recommendations of European LeukemiaNet (ELN). Patients were defined as remission failure if BCR-ABL transcripts >10% after 6 months (T6), >1% after 12 months (T12), and >0.1% after 18 (T18) months of treatment. The logistic regression was used to determine the optimal cut-off point of each marker and test the association of marker level with remission failure. RESULTS: The median NRBC, white blood cells, blast cells, basophils, and platelets were declined parallel with the decreases of BCR-ABL transcripts in bone marrow cells after 6 months of treatment (P<0.001). In addition, NRBC was almost not found in the blood of patients who archived good response at T6, T12, and T18 time-points. Interestingly, patients with a high level of NRBC (cut-off: 0.003×109/L) have higher BCR-ABL transcripts compared to others. The elevated NRBC at T6 (OR=6.49, P=0.042), T12 (OR=6.73, P=0.007), and T18 (OR=5.96, P=0.009) time-points was identified as an independent factor for the remission failure. CONCLUSION: The results of this study showed that a high number of NRBC in peripheral blood of CML patients is associated with higher BCR-ABL transcripts in bone marrow cells. The elevated NRBC might serve as an independent marker for molecular remission failure in CML.

EGFR plasma mutation in prediction models for resistance with EGFR TKI and survival of non-small cell lung cancer.

BACKGROUND: This study aims to clarify the prognostic role of epidermal growth factor receptor (EGFR) mutations in plasma of non-small cell lung cancer (NSCLC) for resistance to tyrosine kinase inhibitor (TKI), in correlation with clinical characteristics. A total of 94 Adenocarcinoma, clinical stage IV NSCLC patients with either E19del or L858R mutation were admitted to the prospective study from Jan-2016 to Jul-2018. EGFR mutations in plasma were detected by scorpions ARMS method. The Kaplan-Meier and Cox regression methods were used to estimate and test the difference of progression-free survival (PFS) and overall survival (OS) between groups. The prognostic power of each factor was appraised by the Bayesian Model Averaging (BMA) method. RESULTS: Among 94 patients, 28 cases still are good responses according to the RECIST criteria and negative for EGFR mutations in plasma. Of 66 resistant patients, EGFR mutations were positive in plasma of 57 cases (86.4%) which was higher than the value of pre-treatment (48.5%). Of which, 17 patients (25.8%) have the occurrence of EGFR mutations in plasma earlier than progression 2.1 (0.6-7.9) months. The secondary T790M mutation was found in the plasma of 32 cases (48.5%). Median PFS and OS for the study subjects were 12.9 (11.0-14.2) and 29.5 (25.2-41.3) months, respectively. The post-treatment EGFR plasma test with brain and new metastasis were detected as independent prognostic factors for worse PFS (P = 0.008, 0.016 and 0.028, respectively). While EGFR plasma (P = 0.044) with bone metastasis at baseline (P = 0.012), new metastasis (P = 0.003), and high cfDNA concentration (P = 0.004) serve as the worse survival factors, surgery treatment helps to prolong OS in NSCLC treated with EGFR TKI (P = 0.012). BMA analysis identified EGFR plasma test as the strongest prognostic factor for both PFS and OS (possibility of 100% and 99.7%, respectively). CONCLUSIONS: EGFR plasma test is the powerfully prognostic factor for early resistance with EGFR TKI and worse survival in NSCLC regardless of clinical characteristics.

The prognostic impact of neutrophil to lymphocyte ratio in advanced non-small cell lung cancer patients treated with EGFR TKI.

PURPOSE: To identify and clarify the roles of inflammatory markers in prognosis for advanced non-small cell lung cancer (NSCLC) patients treated with EGFR tyrosine kinase inhibitor (TKI). PATIENTS AND METHODS: One hundred and twelve adenocarcinoma, clinical stage IV, NSCLC patients with either EGFR exon 19 deletion (E19del) or EGFR exon 21 L858R substitution mutation (L858R) were selected for this study. The blood cell count at different stages of treatment was used to calculate the inflammatory markers. The Kaplan-Meier statistics and Cox regression model were used to test the differences of progression-free survival (PFS) between groups by the optimal cutoff point of biomarkers. RESULTS: The median values of white blood cell (WBC), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR) and platelet to lymphocyte ratio (PLR) in NSCLC patients tended to be reduced after 3 months treated with EGFR TKI and increased conversely when the disease develops progression (P<0.001). With an optimal cutoff point of 2.96, NLR is the best prognostic marker in prediction of clinical response among the investigated markers (area under the curve [AUC]=0.873, 95% CI: 0.821-0.926, P<0.001), and it is an independent predictive marker (OR=3.52, 95% CI: 1.42-8.71, P<0.001). With optimal cutoff point of 0.38, MLR is also a predictive marker in response evaluation (AUC=0.762, 95% CI: 0.691-0.832). Univariate analyses have shown that the larger tumor size (>3cm) and the high level of pretreatment NLR were associated with the shortening of PFS (HR=2.24, 95% CI: 1.04-4.83, P=0.039 and HR=2.67, 95% CI: 1.41-5.03, P=0.006, respectively). Multivariate analysis has shown that the elevated NLR is an independent prognostic marker for worse PFS of NSCLC patients treated with EGFR TKI (HR=2.15, 95% CI: 1.15-3.99, P=0.016). CONCLUSION: NLR and MLR are valuable markers in response evaluation for NSCLC patients treated with EGFR TKI. The elevated NLR is also an independent prognostic factor for worse survival.