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Despite the discovery of several bacteria capable of interacting with polymers, the activity of the natural bacterial isolates is limited. Furthermore, there is a lack of knowledge regarding the development of bioprocesses for polyethylene (PE) degradation. Here, we report a bioprocess using pseudo-resting cells for efficient degradation of PE. The bacterial strain Acinetobacter nosocomialis was isolated from PE-containing landfills and characterized using low-density PE (LDPE) surface oxidation when incubated with LDPE. We optimized culture conditions to generate catalytic pseudo-resting cells of A. nosocomialis that are capable of degrading LDPE films in a bioreactor. After 28 days of bioreactor operation using pseudo-resting cells of A. nosocomialis, we observed the formation of holes on the PE film (39 holes per 217 cm2, a maximum diameter of 1440 µm). This study highlights the potential of bacteria as biocatalysts for the development of PE degradation processes. KEY POINTS: ⢠New bioprocess has been proposed to degrade polyethylene (PE). ⢠Process with pseudo-resting cells results in the formation of holes in PE film. ⢠We demonstrated PE degradation using A. nosocomialis as a biocatalyst.
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Acinetobacter , Polietileno , Reactores Biológicos , CatálisisRESUMEN
OBJECTIVES: To evaluate a CT-based radiomics model for identifying malignant pancreatic intraductal papillary mucinous neoplasms (IPMNs) and compare its performance with the 2017 international consensus guidelines (ICGs). MATERIALS AND METHODS: We retrospectively included 194 consecutive patients who underwent surgical resection of pancreatic IPMNs between January 2008 and December 2020. Surgical histopathology was the reference standard for diagnosing malignancy. Using radiomics features from preoperative contrast-enhanced CT, a radiomics model was built with the least absolute shrinkage and selection operator by a five-fold cross-validation. CT and MR images were independently reviewed based on the 2017 ICGs by two abdominal radiologists, and the performances of the 2017 ICGs and radiomics model were compared. The areas under the curve (AUCs) were compared using the DeLong method. RESULTS: A total of 194 patients with pancreatic IPMNs (benign, 83 [43%]; malignant, 111 [57%]) were chronologically divided into training (n = 141; age, 65 ± 8.6 years; 88 males) and validation sets (n = 53; age, 66 ± 9.7 years; 31 males). There was no statistically significant difference in the diagnostic performance of the 2017 ICGs between CT and MRI (AUC, 0.71 vs. 0.71; p = 0.93) with excellent intermodality agreement (k = 0.86). In the validation set, the CT radiomics model had higher AUC (0.85 vs. 0.71; p = 0.038), specificity (84.6% vs. 61.5%; p = 0.041), and positive predictive value (84.0% vs. 66.7%; p = 0.044) than the 2017 ICGs. CONCLUSION: The CT radiomics model exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. CLINICAL RELEVANCE STATEMENT: Compared with the radiologists' evaluation based on the 2017 international consensus guidelines, the CT radiomics model exhibited better diagnostic performance in classifying malignant intraductal papillary mucinous neoplasms. KEY POINTS: ⢠There is a paucity of comparisons between the 2017 international consensus guidelines (ICGs) and radiomics models for malignant intraductal papillary mucinous neoplasms (IPMNs). ⢠The CT radiomics model developed in this study exhibited better diagnostic performance than the 2017 ICGs in classifying malignant IPMNs. ⢠The radiomics model may serve as a valuable complementary tool to the 2017 ICGs, potentially allowing a more quantitative assessment of IPMNs.
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Carcinoma Ductal Pancreático , Neoplasias Quísticas, Mucinosas y Serosas , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Humanos , Masculino , Persona de Mediana Edad , Anciano , Radiómica , Estudios Retrospectivos , Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnósticoRESUMEN
In this study, we developed a model to predict culture test results for pulmonary tuberculosis (PTB) with a customized multimodal approach and evaluated its performance in different clinical settings. Moreover, we investigated potential performance improvements by combining this approach with deep learning-based automated detection algorithms (DLADs). This retrospective observational study enrolled patients over 18 years of age who consecutively visited the level 1 emergency department and underwent chest radiograph and sputum testing. The primary endpoint was positive sputum culture for PTB. We compared the performance of the diagnostic models by replacing radiologists' interpretations of chest radiographs with screening scores calculated through DLAD. The optimal diagnostic model had an area under the receiver operating characteristic curve of 0.924 (95% CI 0.871-0.976) and an area under precision recall curve of 0.403 (95% CI 0.195-0.580) while maintaining a specificity of 81.4% when sensitivity was fixed at 90%. Multicomponent models showed improved performance for detecting PTB when chest radiography interpretation was replaced by DLAD. Multicomponent diagnostic models with DLAD customized for different clinical settings are more practical than traditional methods for detecting patients with PTB. This novel diagnostic approach may help prevent the spread of PTB and optimize healthcare resource utilization in resource-limited clinical settings.
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Aprendizaje Profundo , Tuberculosis Pulmonar , Adulto , Humanos , Algoritmos , Pulmón , Radiografía Torácica/métodos , Estudios Retrospectivos , Sensibilidad y Especificidad , Tuberculosis Pulmonar/diagnóstico por imagenRESUMEN
Analytical methods based on the mass balance approach were developed for the purity evaluation of tetracycline hydrochloride, a representative salt compound used in pure veterinary drug analysis. The purity assignment method was used to quantify individual classes of impurities via independent analytical techniques. The mass fraction of the free base or salt form contained in a high-purity organic compound with a hydrochloride salt can be determined. The chloride content by ion chromatography-conductivity detector (IC-CD) and general classes of impurities, including structurally related impurities by liquid chromatography-ultraviolet (LC-UV) detector, water by Karl Fischer (KF) coulometric titration, residual solvents by headspace sampler gas chromatography/mass spectrometry (HS-GC/MS), and non-volatiles by thermogravimetric analyzer (TGA), were considered to calculate the purity of the mass fraction. The chloride content of the salt compound can be considered the main impurity in the mass fraction of the free base in the salt compound. A purity assay using quantitative nuclear magnetic resonance (q-NMR) as a direct determination method was performed to confirm the results of the mass balance method. The assigned purities of the tetracycline free form and its salt form in mass fraction were (898.80 ± 1.60) mg/g and (972.65 ± 1.58) mg/g, respectively, which are traceable to the international system of units (SI). Thus, the procedure for evaluating the purity of the free base and salt forms in the salt compound is newly demonstrated in this study.
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Cloruros , Tetraciclina , Cromatografía Liquida/métodos , Cromatografía de Gases y Espectrometría de MasasRESUMEN
Phthalates are mainly used as plasticizers in polyvinyl chloride (PVC). However, prolonged exposure to phthalates poses considerable risks to human health. Consequently, the utilization of phthalates in consumer products is subject to regulations, with a defined threshold of 0.1 %. In this study, we developed an accurate and simultaneous method for determination of 11 representative phthalates and a non-phthalate plasticizer (di(2-ethylhexyl) terephthalate, DEHT) in PVC as a higher-order reference method. Homogeneously prepared PVC samples, each containing approximately 0.1 % of the target plasticizer compounds, were analyzed using gas chromatography-mass spectrometry (GC-MS) with deuterium-labeled phthalates and DEHT. The developed method could effectively separate and quantify all target plasticizers without interference with each other and potential overlap between the isomeric forms of phthalates, di-isodecyl phthalate, and di-isononyl phthalate. The developed method has high-order metrological quality, exhibiting exceptional selectivity, accuracy, repeatability (≤ 2.17 %), reproducibility (≤ 2.16 %), and relative expanded uncertainty (≤ 5.6 %). This analytical method is thus suitable for accurately assessing the target plasticizer levels in PVC products for ensuring compliance with the established 0.1 % threshold. This method was successfully applied to quantify twelve distinct plasticizers in PVC products obtained from the Korean market, validating its effectiveness and reliability in real-world scenarios.
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Dietilhexil Ftalato , Ácidos Ftálicos , Humanos , Plastificantes/análisis , Cloruro de Polivinilo/química , Reproducibilidad de los Resultados , Ácidos Ftálicos/análisis , Espectrometría de Masas , Cromatografía de Gases y Espectrometría de Masas/métodos , Isótopos , Dietilhexil Ftalato/análisisRESUMEN
Bone marrow-derived human mesenchymal stem cells (hMSCs) can differentiate into various lineages, such as chondrocytes, adipocytes, osteoblasts, and neuronal lineages. It has been shown that the high-efficiency DNA-repair capacity of hMSCs is decreased during their differentiation. However, the underlying its mechanism during adipogenesis and osteogenesis is unknown. Herein, we investigated how alkyl-damage repair is modulated during adipogenic and osteogenic differentiation, especially focusing on the base excision repair (BER) pathway. Response to an alkylation agent was assessed via quantification of the double-strand break (DSB) foci and activities of BER-related enzymes during differentiation in hMSCs. Adipocytes showed high resistance against methyl methanesulfonate (MMS)-induced alkyl damage, whereas osteoblasts were more sensitive than hMSCs. During the differentiation, activities, and protein levels of uracil-DNA glycosylase were found to be regulated. In addition, ligation-related proteins, such as X-ray repair cross-complementing protein 1 (XRCC1) and DNA polymerase ß, were upregulated in adipocytes, whereas their levels and recruitment declined during osteogenesis. These modulations of BER enzyme activity during differentiation influenced DNA repair efficiency and the accumulation of DSBs as repair intermediates in the nucleus. Taken together, we suggest that BER enzymatic activity is regulated in adipogenic and osteogenic differentiation and these alterations in the BER pathway led to different responses to alkyl damage from those in hMSCs.
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Adipogénesis , Células Madre Mesenquimatosas , Humanos , Adipogénesis/genética , Osteogénesis/fisiología , Médula Ósea/metabolismo , Células Cultivadas , Diferenciación Celular/fisiología , Reparación del ADN , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/metabolismoRESUMEN
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a CNS autoimmune disease affecting the brain, spinal cord, and optic nerve. The neutrophil-to-lymphocyte ratio (NLR) is related to autoimmune disease activity. However, the clinical implication of index ratios such as the NLR is unclear in patients with MOGAD. OBJECTIVES: We investigated the relationship between index ratios such as the NLR and disease activity and disability to discover the index that best correlates with an attack in MOGAD. METHODS: Using a CNS demyelinating disease cohort, we reviewed 39 patients with MOGAD (age 37.4 ± 12.0 years; F:M = 20:19) who had 390 blood samples available for cell count analysis. We calculated the NLR, eosinophil-to-lymphocyte-ratio (ELR), platelet-to-lymphocyte-ratio (PLR), monocyte-to-lymphocyte ratio (MLR), basophil-to-lymphocyte ratio (BLR), and neutrophil percentage (N%) [neutrophil count (/mm3) / WBC (/mm3) x 100 (%)]. We investigated the associations between each index ratio and disease activity and disability using the receiver operating characteristic (ROC) curve, machine learning program (kNN algorithm), and generalized estimating equations (GEE) analysis. RESULTS: In patients with MOGAD, the NLR, PLR, and N% were higher and ELR was lower during an attack than in remission (all p<0.001). The areas under the ROC curve for the NLR, ELR, PLR, and N% were 0.68, 0.69, 0.61, and 0.68, respectively, with the highest sensitivity of 76.0% in the ELR and the highest specificity of 76.3% in the N%. The classification accuracy scores of the kNN machine learning algorithm were 71% for the NLR, 62% for the ELR, 63% for the PLR, and 72% for the N%. In the GEE analysis of attack samples, both the NLR and treatment-naive had positive associations with the Expanded Disability Status Scale (EDSS) score (ß=0.137, p = 0.008 and ß=1.142, p = 0.003, respectively), and the PLR was negatively associated with the EDSS score (ß=-0.004, p = 0.022). DISCUSSION: Our study suggests that the novel index, neutrophil% is the simplest and the most useful marker to differentiate between attack and remission and shows comparable reliability with NLR in MOGAD. Moreover, the NLR and PLR could be used as supportive biomarkers for disease disability during an attack in patients with MOGAD.
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Enfermedades Autoinmunes , Neutrófilos , Humanos , Reproducibilidad de los Resultados , Recuento de Leucocitos , Linfocitos , Anticuerpos , Estudios Retrospectivos , PronósticoRESUMEN
A certified reference material (CRM), KRISS CRM 108-02-006, was developed for the accurate analysis of low levels of acrylamide in infant formula matrices. The CRM is an infant formula fortified with acrylamide at a similar level as that stipulated by the European Union regulation for baby food. Commercially available infant formulas were processed by freeze-drying, and the subsequent homogenization of the fortified material to produce 961 bottles of the CRM in one batch. The CRM bottles containing approximately 15 g of the material in each unit were stored in a storage room at - 70 â. High-purity acrylamide was used as the primary reference material, and its purity was assessed using an in-house mass-balance method to obtain results metrologically traceable to the International System of Units. The acrylamide content of the infant formula CRM was evaluated using isotope dilution-liquid chromatography/mass spectrometry as a reference method, which was established by our research group. An acrylamide content of 55.7 ± 2.1 µg/kg was assigned as the certified value of the CRM with the expanded uncertainty at a 95% confidence level. The homogeneity study showed good uniformity of the acrylamide content among units, providing a relative standard deviation of 1.2% of the mean value. A stability study was also performed by monitoring the CRM under different temperature conditions and periods. The stability results indicated that the acrylamide content in the CRM under the storage conditions of - 70 â remained stable for up to 10 months.
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Acrilamida , Fórmulas Infantiles , Lactante , Humanos , Estándares de Referencia , Cromatografía Liquida/métodos , Espectrometría de Masas/métodosRESUMEN
The exposure of cumulus cells to nuclear matured oocytes can be regulated through the forced delay of nuclear maturation or the alteration of in vitro maturation (IVM) time in cumulus-oocyte complexes (COCs). However, to date, no evidence has been presented for the enhancement of cytoplasmic maturation by them, indicating irrelevance of cumulus cells in cytoplasmic maturation. Therefore, in order to identify the requirement of cumulus cells in achieving the cytoplasmic maturation of immature oocytes, this study investigated the effects of cumulus cells on the in vitro cytoplasmic maturation of oocytes within COCs derived from porcine medium antral follicles (MAFs) post-the completion of nuclear maturation. For these, with IVM of COCs for 44 h (control), cumulus cell-free oocytes with completed nuclear maturation were in-vitro-matured additionally for 0, 6, or 12 h, and then a variety of factors representing the cytoplasmic maturation of oocytes were analyzed and compared. As the results, the IVM of COCs for 32 h showed complete nuclear maturation and incomplete cytoplasmic maturation. Moreover, after the removal of cumulus cells from COCs with the completion of nuclear maturation, IVM for an additional 6 or 12 h resulted in significant increases in the size of the perivitelline space, the proportion of oocytes with a normal intracellular mitochondrial distribution and a normal round first polar body, and the preimplantation development into the 2-cell and blastocyst stages after parthenogenetic activation. Simultaneously, they showed significant reduction in the level of intracellular reactive oxygen species and no significant differences in the total number of blastocysts. Furthermore, oocytes obtained by this approach did not significantly differ from control oocytes produced by IVM of COCs for 44 h. Our results demonstrate that the cumulus cells enclosing COCs derived from porcine MAFs are not essential for the completion of cytoplasmic maturation after complete nuclear maturation by COCs.
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Técnicas de Maduración In Vitro de los Oocitos , Oocitos , Femenino , Porcinos , Animales , Técnicas de Maduración In Vitro de los Oocitos/veterinaria , Técnicas de Maduración In Vitro de los Oocitos/métodos , Oocitos/fisiología , Folículo Ovárico , Citoplasma , Desarrollo Embrionario , Células del Cúmulo/fisiologíaRESUMEN
BACKGROUND. When coronary CTA is performed in the emergency department (ED), the use of a contemporary scanner with improved temporal resolution may eliminate the need to administer ß-blockers for heart rate (HR) control, thereby expediting workup. OBJECTIVE. The purpose of this study was to compare ED length of stay (LOS), image quality, frequency of nondiagnostic examinations, and other clinical outcomes between patients undergoing coronary CTA in the ED on a single-source CT (SSCT) scanner with HR control versus on a dual-source CT (DSCT) scanner without HR control. METHODS. This retrospective study included 509 patients (283 men, 226 women; mean age, 52.1 ± 15.1 [SD] years) at low to intermediate risk for acute coronary syndrome who underwent coronary CTA for acute chest pain during off-hours in a single ED from March 1, 2020, to April 25, 2022. A total of 205 patients initially underwent CTA using a 64-detector-row SSCT scanner with HR control (oral ß-blocker administration if HR was > 65 beats/min); after scanner replacement on April 26, 2021, 304 patients underwent CTA using a third-generation DSCT without HR control. Groups were compared in terms of ED LOS and CT completion time (defined as time from ordering CTA to completion of acquisition) using propensity score matching and additional endpoints including image quality and nondiagnostic examinations based on radiology reports. RESULTS. The DSCT group, compared with the SSCT group, showed no significant difference in median ED LOS (505 vs 457 minutes, respectively; p = .37) but showed shorter median CT completion time (95 vs 117 minutes, p < .001); on the basis of a mediation analysis, 89% of the reduction in CT completion time for DSCT was attributed to the absence of HR control. The DSCT group, compared with the SSCT group, showed higher frequency of examinations with good or excellent image quality (87.8% vs 60.0%, p < .001) and lower frequency of nondiagnostic examinations (1.6% vs 6.3%, p = .01) but showed no significant difference in frequencies of emergent cardiology consultation, invasive angiography, ED disposition, or coronary revascularization (all p > .05). No patient in either group experienced 30-day all-cause mortality or a major adverse cardiovascular event. CONCLUSION. The use of a DSCT scanner for coronary CTA can eliminate the need for ß-blocker administration for HR control while decreasing nondiagnostic examinations. CLINICAL IMPACT. A DSCT scanner can expedite clinical processes in the ED.
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Dolor en el Pecho , Corazón , Masculino , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Angiografía Coronaria/métodos , Estudios Retrospectivos , Dolor en el Pecho/diagnóstico por imagen , Servicio de Urgencia en Hospital , Dosis de RadiaciónRESUMEN
Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions. Conclusions: Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).
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Aminas , Gastritis , Humanos , Aminas/uso terapéutico , Gastritis/tratamiento farmacológico , Hemorragia , Edema , Método Doble Ciego , Resultado del TratamientoRESUMEN
A corn flour certified reference material (KRISS CRM 108-01-011) was developed to ensure accurate and reliable measurements of type B trichothecenes (deoxynivalenol, nivalenol, 3-acetyldeoxynivalenol, 15-acetyldeoxynivalenol), and deoxynivalenol-3-glucoside. The material was freeze-dried, ground, sieved, and well-mixed. The final produced CRM was packaged at 14 g per unit and stored at -70 °C. The certification was performed using isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS). For simultaneous characterization and homogeneity assessments, ten units were randomly selected and analyzed. The among-unit relative standard deviations were below 1 % for all mycotoxins, indicating excellent homogeneity of the CRM. The stability of the CRM was also assessed at various designated temperatures and test periods. The uncertainties of the certified values varied between 2.4 % and 6.2 %, thereby confirming their higher-order metrological quality to provide references for testing laboratories. In case of deoxynivalenol-3-glucoside, an information value was assigned due to the lack of its traceability to the SI units.
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Tricotecenos Tipo B , Zea mays , Cromatografía Liquida/métodos , Zea mays/química , Espectrometría de Masas en Tándem/métodos , Certificación , Estándares de ReferenciaRESUMEN
CONTEXT: Despite the absence of light within the body, the application of microscopy during stages of in vitro embryo production has led to the discovery of light irradiation effects on embryo preimplantation development. AIMS: To determine the optimal light irradiation wavelengths at various embryo stages for improving the preimplantation development of mouse embryos and the quality (total cell number) of blastocysts. METHOD: All in vitro procedures of zygote or 2-cell embryo manipulation, embryo monitoring, and culture medium exchange were conducted under visible (390-750nm), blue (445-500nm), green (500-575nm), yellow (575-585nm), or red (620-750nm) light irradiation wavelength. KEY RESULTS: We found that blue, green, and yellow light irradiation during in vitro blastocyst production from zygotes significantly improved blastocyst production and quality, compared to visible and red light irradiation. However, 2-cell embryos exposed to yellow light during in vitro blastocyst production produced significantly more high-quality blastocysts than did 2-cell embryos exposed to visible, blue, green, or red light. After exposure to blue and green - but not yellow - light during in vitro zygote manipulation, yellow light irradiation during embryo monitoring and culture medium exchange triggered significant retardation of preimplantation development. CONCLUSION: These results demonstrate that yellow light irradiation during in vitro blastocyst production, regardless of embryo stage, improves preimplantation development of mouse embryos. IMPLICATIONS: The present study will contribute to produce greater high-quality blastocysts and reduce experimental errors generated by light exposure during mouse embryo-related studies.
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Blastocisto , Embrión de Mamíferos , Desarrollo Embrionario , Luz , Animales , Blastocisto/efectos de la radiación , Medios de Cultivo , Embrión de Mamíferos/efectos de la radiación , Desarrollo Embrionario/efectos de la radiación , Luz/efectos adversos , Ratones , CigotoRESUMEN
BACKGROUND: Investigations for programmed cell death-1 (PD-1) blockade-induced hyperprogressive disease (HPD) have not been stringently conducted in patients with advanced gastric cancer (AGC). We explored the occurrence of HPD and its clinical implications in patients with AGC and treated with PD-1 inhibitors. METHODS: We enrolled 169 patients with AGC and treated with either the PD-1 blockade (nivolumab or pembrolizumab; N = 112) or irinotecan monotherapy (N = 57) as a single agent. Tumour growth dynamics based on tumour growth kinetics and tumour growth rate (TGR) and time to treatment failure were analysed to define HPD. The incidence, clinical consequences and predictive markers of HPD were investigated. RESULTS: The optimal criteria for HPD were 4-fold increases in both tumour growth kinetics and TGR ratios and a 40% increase in TGR based on the analysis for patients treated with irinotecan. In total, 10.7% (12/112) of patients experienced HPD after PD-1 inhibitor treatment. Patients with HPD had both shorter progression-free survival (hazard ratio: 2.318; 95% confidence interval: 1.205-4.460) and overall survival (hazard ratio: 2.542; 95% confidence interval: 1.314-4.918) than patients with progressive disease without HPD, losing opportunities for subsequent systemic treatments. Although other variables including PD-L1 expression were not associated with the occurrence of HPD, hypoalbuminemia (<3.25 mg/dL) at baseline was significantly associated with the occurrence of HPD (P < 0.001) and inferior survival outcomes. CONCLUSIONS: HPD occurs in a proportion of patients with AGC and treated with PD-1 inhibitors. PD-1 inhibitor-induced HPD is associated with worse outcome, loss of eligibility for subsequent treatment and hypoalbuminemia, warranting further investigation.
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Hipoalbuminemia , Neoplasias Gástricas , Progresión de la Enfermedad , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Irinotecán/efectos adversos , Receptor de Muerte Celular Programada 1 , Neoplasias Gástricas/tratamiento farmacológicoRESUMEN
Background Preoperative assessment of pathologic complete response (pCR) in locally advanced rectal cancer (LARC) after neoadjuvant chemoradiotherapy (nCRT) is increasingly needed for organ preservation, but large-scale validation of an MRI radiomics model remains lacking. Purpose To evaluate radiomics models based on T2-weighted imaging and diffusion-weighted MRI for predicting pCR after nCRT in LARC and compare their performance with visual assessment by radiologists. Materials and Methods This retrospective study included patients with LARC (clinical stage T3 or higher, positive nodal status, or both) who underwent post-nCRT MRI and elective resection between January 2009 and December 2018. Surgical histopathologic analysis was the reference standard for pCR. Radiomic features were extracted from the volume of interest on T2-weighted images and apparent diffusion coefficient (ADC) maps from post-nCRT MRI to generate three models: T2 weighted, ADC, and both T2 weighted and ADC (merged). Radiomics signatures were generated using the least absolute shrinkage and selection operator with tenfold cross-validation. Three experienced radiologists independently rated tumor regression grades at MRI and compared these with the radiomics models' diagnostic outcomes. Areas under the curve (AUCs) of the radiomics models and pooled readers were compared by using the DeLong method. Results Among 898 patients, 189 (21%) achieved pCR. The patients were chronologically divided into training (n = 592; mean age ± standard deviation, 59 years ± 12; 388 men) and test (n = 306; mean age, 59 years ± 12; 190 men) sets. The radiomics signatures of the T2-weighted, ADC, and merged models demonstrated AUCs of 0.82, 0.79, and 0.82, respectively, with no evidence of a difference found between the T2-weighted and merged models (P = .49), while the ADC model performed worse than the merged model (P = .02). The T2-weighted model had higher classification performance (AUC, 0.82 vs 0.74 [P = .009]) and sensitivity (80.0% vs 15.6% [P < .001]), but lower specificity (68.4% vs 98.6% [P < .001]) than the pooled performance of the three radiologists. Conclusion An MRI-based radiomics model showed better classification performance than experienced radiologists for diagnosing pathologic complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Taylor in this issue.
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Neoplasias del Recto , Quimioradioterapia , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante/métodos , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Malnutrition leads to adverse effects on the short- and long-term prognosis in patients with periampullary diseases who underwent surgery. Nutritional risk indicators based on albumin and body weight have been developed to evaluate nutritional status and nutritional therapy efficacy, but no standard objective measurement has been devised to evaluate nutritional status during the early period after pancreaticoduodenectomy (PD). Therefore, this study aimed to assess the efficacy of total parenteral nutrition (TPN) during the early postoperative period after PD. METHODS: We analyzed 28 patients with a periampullary disease-common bile duct cancer, ampulla of Vater cancer, pancreatic head cancer, neuroendocrine tumor, chronic pancreatitis-who have undergone PD from Jan. 1, 2012 to Dec. 31, 2016. For all the patients, TPN was administered from postoperative day (POD) 1 at 25 Kcal/kg ideal body weight. Various nutritional indicators were measured such as Body mass index, nutritional risk index, protein, albumin, prealbumin, C-reactive protein. The volume of skeletal muscle area, muscle density, visceral and subcutaneous fat areas were assessed two times, preoperatively and on POD 7 by CT scan at the 3rd lumbar spine (L3) level. RESULTS: Average age of the 28 study subjects (18 males and 10 females) was 63.5±9.7 years. Although there is no difference in BMI between preoperative result and POD 7, protein, albumin, and prealbumin levels were significantly lower POD 7 the preoperative (P<0.001), but CRP was higher (P<0.001), and prealbumin and CRP levels were negatively correlated (R=-0.682, P<0.01). Muscle mass increased postoperatively (P=0.02), but the amount of visceral fat decreased (P=0.00). Based on CRP, and muscle density results, muscle, visceral and subcutaneous fat masses did not change after PD. CONCLUSIONS: In order to evaluate the nutritional status accurately after the hepato-biliary radical surgery, we suggest the muscle and fat mass measurement that can adjust the degree of inflammation during the early postoperative period.
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BACKGROUND: Interpretation of chest radiographs (CRs) by emergency department (ED) physicians is inferior to that by radiologists. Recent studies have investigated the effect of deep learning-based assistive technology on CR interpretation (DLCR), although its relevance to ED physicians remains unclear. This study aimed to investigate whether DLCR supports CR interpretation and the clinical decision-making of ED physicians. METHODS: We conducted a prospective interventional study using a web-based performance assessment system. Study participants were recruited through the official notice targeting board for certified emergency physicians and residents working at the present ED. Of the eight ED physicians who volunteered to participate in the study, seven ED physicians were included, while one participant declared withdrawal during performance assessment. Seven physicians' CR interpretations and clinical decision-making were assessed based on the clinical data from 388 patients, including detecting the target lesion with DLCR. Participant performance was evaluated by area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and accuracy analyses; decision-making consistency was measured by kappa statistics. ED physicians with < 24 months of experience were defined as 'inexperienced'. RESULTS: Among the 388 simulated cases, 259 (66.8%) had CR abnormality. Their median value of abnormality score measured by DLCR was 59.3 (31.77, 76.25) compared to a score of 3.35 (1.57, 8.89) for cases of normal CR. There was a difference in performance between ED physicians working with and without DLCR (AUROC: 0.801, P < 0.001). The diagnostic sensitivity and accuracy of CR were higher for all ED physicians working with DLCR than for those working without it. The overall kappa value for decision-making consistency was 0.902 (95% confidence interval [CI] 0.884-0.920); concurrently, the kappa value for the experienced group was 0.956 (95% CI 0.934-0.979), and that for the inexperienced group was 0.862 (95% CI 0.835-0.889). CONCLUSIONS: This study presents preliminary evidence that ED physicians using DLCR in a clinical setting perform better at CR interpretation than their counterparts who do not use this technology. DLCR use influenced the clinical decision-making of inexperienced physicians more strongly than that of experienced physicians. These findings require prospective validation before DLCR can be recommended for use in routine clinical practice.
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Aprendizaje Profundo , Médicos , Dispositivos de Autoayuda , Servicio de Urgencia en Hospital , Humanos , Radiografía TorácicaRESUMEN
An analytical method was developed for the accurate determination of eight polycyclic aromatic hydrocarbons (PAHs) in extruded high-impact polystyrene (HIPS) as a higher-order reference method. Uncleaned HIPS matrix rendered the accurate quantitation impossible and hampered the repeatability of the gas chromatography/mass spectrometry (GC/MS) measurement. This led to a bias in the results and increased the measurement uncertainty. Extracts were sufficiently purified through a two-step process: (i) dissolution and precipitation and (ii) molecularly imprinted polymers-solid phase extraction for clean-up. Co-elution of indeno(1,2,3-cd)pyrene (IP), dibenz(a,h)anthracene (DBahA), and their 13C6-labeled isotopes resulted in a bias in the area ratios of IP/13C6-IP and DBahA/13C6-DBahA, thus increasing the measurement uncertainty. An optimized GC condition using an Rxi-PAH column improved the peak separation of IP and DBahA and their isotopes, thus improving the quality of the measurement. The optimized method was validated using PAH (0.36-0.45 mg/kg)-containing HIPS pellets. The optimized method had excellent repeatability (<2%) and reproducibility (<3%) for concentrations less than 0.5 mg/kg of the eight PAHs in HIPS. Using the optimized method, the relative expanded uncertainties for all the target PAHs were below 5% (with a 95% level of confidence).
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Hidrocarburos Policíclicos Aromáticos , Cromatografía de Gases y Espectrometría de Masas/métodos , Isótopos , Hidrocarburos Policíclicos Aromáticos/análisis , Poliestirenos/análisis , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND & AIMS: Despite the clinical and genetic significance of macrotrabecular-massive hepatocellular carcinoma (MTM-HCC), its characteristics on imaging have not been described. This study aimed to characterise MTM-HCC on gadoxetic acid-enhanced MRI and to evaluate the diagnostic accuracy and prognostic value of these imaging characteristics. METHODS: We enrolled 3 independent cohorts from 2 tertiary care centres. The 3 cohorts consisted of a total of 476 patients who underwent gadoxetic acid-enhanced MRI and surgical resection for treatment-naïve single HCCs. Independent review of histopathology and MRI by 2 reviewers was performed for each cohort, and inter-reader agreement was evaluated. Based on the result of MRI review in the training cohort (cohort 1), we developed 2 diagnostic criteria for MTM-HCC and evaluated their prognostic significance. The diagnostic performance and prognostic significance were validated in 2 validation cohorts (cohorts 2 and 3). RESULTS: We developed 2 diagnostic MRI criteria (MRIC) for MTM-HCC: MRIC-1, ≥20% arterial phase hypovascular component; MRIC-2, ≥50% hypovascular component and 2 or more ancillary findings (intratumoural artery, arterial phase peritumoural enhancement, and non-smooth tumour margin). MRIC-1 showed high sensitivity and negative predictive value (88% and 95% in the training cohort, and 88% and 97% in the pooled validation cohorts, respectively), whereas MRIC-2 demonstrated moderate sensitivity and high specificity (47% and 94% in the training cohort, and 46% and 96% in the pooled validation cohorts, respectively). MRIC-2 was an independent poor prognostic factor for overall survival in both training and pooled validation cohorts. CONCLUSIONS: Using gadoxetic acid-enhanced MRI findings, including an arterial phase hypovascular component, we could stratify the probability of MTM-HCC and non-invasively obtain prognostic information. LAY SUMMARY: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a histopathologic subtype of HCC characterised by aggressive biological behaviour and poor prognosis. We developed imaging criteria based on liver MRI that could be used for the non-invasive diagnosis of MTM-HCC. HCCs showing imaging findings of MTM-HCC were associated with poor outcomes after hepatic resection.