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Given the previous SARS-CoV-2 pandemic and the inherent unpredictability of viral antigenic drift and shift, preemptive development of diverse neutralizing antibodies targeting a broad spectrum of epitopes is essential to ensure immediate therapeutic and prophylactic interventions during emerging outbreaks. In this study, we present a monoclonal antibody engineered for cross-reactivity to both wild-type and Delta RBDs, which, surprisingly, demonstrates enhanced neutralizing activity against the Omicron variant despite a significant number of mutations. Using an Escherichia coli inner membrane display of a human naïve antibody library, we identified antibodies specific to the wild-type SARS-CoV-2 receptor binding domain (RBD). Subsequent directed evolution via yeast surface display yielded JS18.1, an antibody with high binding affinity for both the Delta and Kappa RBDs, as well as enhanced binding to other RBDs (wild-type, Alpha, Beta, Gamma, Kappa, and Mu). Notably, JS18.1 (engineered for wild-type and Delta RBDs) exhibits enhanced neutralizing capability against the Omicron variant and binds to RBDs noncompetitively with ACE2, distinguishing it from other previously reported antibodies. This underscores the potential of pre-existing antibodies to neutralize emerging SARS-CoV-2 strains and offers insights into strategies to combat emerging viruses.
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Anticuerpos Monoclonales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/virología , Anticuerpos Monoclonales/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/química , Pruebas de Neutralización , Epítopos/inmunología , Mutación , Reacciones Cruzadas/inmunología , Dominios Proteicos/inmunologíaRESUMEN
Despite promising advancements in deep learning in medical domains, challenges still remain owing to data scarcity, compounded by privacy concerns and data ownership disputes. Recent explorations of distributed-learning paradigms, particularly federated learning, have aimed to mitigate these challenges. However, these approaches are often encumbered by substantial communication and computational overhead, and potential vulnerabilities in privacy safeguards. Therefore, we propose a self-supervised masked sampling distillation technique called MS-DINO, tailored to the vision transformer architecture. This approach removes the need for incessant communication and strengthens privacy using a modified encryption mechanism inherent to the vision transformer while minimizing the computational burden on client-side devices. Rigorous evaluations across various tasks confirmed that our method outperforms existing self-supervised distributed learning strategies and fine-tuned baselines.
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Purpose: This study aimed to provide an objective means of predicting treatment responses in patients with schizophrenia using quantitative electroencephalography (qEEG) as an electrophysiological indicator. We obtained qEEG recordings from patients with schizophrenia and explored them for patterns indicative of treatment responsiveness. Patients and Methods: The study included 68 patients had been diagnosed with schizophrenia spectrum disorder. After retrospectively gathering demographic information, clinical data such as qEEG, Positive and Negative Syndrome Scale (PANSS), a multiple regression analysis was performed. This analysis employed baseline qEEG findings as independent variables and PANSS score changes as dependent variables to discern causal relationships. Results: The mean age of the participants was 38.4 years(SD =13.73). The mean PANSS score on admission was 92.97, decreasing to 67.41 at discharge. Multiple regression analysis revealed that delta waves in T4 (ß=0.346, t=3.165, p=0.002), and high-beta waves in Fp2 (ß=0.231, t=2.361, p=0.021) were associated with PANSS changes in absolute power. In addition, the delta waves of O2 (ß=0.250, t=3.288, p=0.002); beta waves of T3 (ß=-1.463, t=-5.423, p<0.001) and O2 (ß=0.551, t=3.366, p=0.001); high beta waves of Fp1 (ß=0.307, t=4.026, p<0.001), T3 (ß=0.855, t=4.414, p<0.001) and T6 (ß=-0.838, t=-4.559, p<0.001) of absolute power using the Z-score were also related to PANSS changes. Pearson's correlation analysis showed that only delta waves at Cz (r= 0.246, p=0.043) in absolute power correlated with changes in the PANSS. Conclusion: We found that certain qEEG wave patterns in patients with schizophrenia prior to antipsychotic treatment were linked to PANSS changes before and after treatment. Delta waves and beta waves, primarily in the frontal and temporal regions, were found to be significantly associated with changes in PANSS scores. In the future, the qEEG indicators identified in this study could serve as electrophysiological markers for predicting antipsychotic treatment responses in patients with schizophrenia.
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PURPOSE: We aimed to develop and investigate positional reproducibility using a fixation device (Unity Brain tumor Immobilization Device [UBID]) in patients with brain tumor undergoing magnetic resonance (MR)-guided radiation therapy (RT) with a 1.5 Tesla (T) MR-linear accelerator (MR-LINAC) to evaluate its feasibility in clinical practice and report representative cases of patients with central nervous system (CNS) tumor. MATERIALS AND METHODS: Quantitative analysis was performed by comparing images obtained by placing only the MR phantom on the couch with those obtained by placing UBID next to the MR phantom. Twenty patients who underwent RT for CNS tumors using 1.5T MR-LINAC between June and October 2022 were retrospectively analyzed. Among them, 5 did not use UBID, whereas 15 used UBID. The positional reproducibility of UBID was evaluated using the median interfractional and intrafractional errors in the first 10 fractions. RESULTS: Each MR quality factor of the MR phantom with UBID satisfied the criteria presented by Elekta. Median values of median shifts in the mediolateral, anteroposterior, and craniocaudal axes for interfractional errors were 2.98, 2.35, and 1.40 mm, respectively. For intrafractional errors, the median values were 0.05, 0.03, and 0.06 mm, respectively. The median values of the median rotations in pitch, roll, and yaw for both interfractional and intrafractional rotations were 0.00°. One patient diagnosed with an optic nerve sheath meningioma received RT with motion monitoring during irradiation. In 2 patients, changes in the tumor cavity and residual lesions were observed in the MRI obtained using 1.5T MR-LINAC on the day of the first treatment and immediately before the 21st fraction, respectively; therefore, offline/online adaptation was performed. CONCLUSIONS: The reproducible and immobile UBID is clinically feasible in patients with CNS tumors receiving RT with 1.5T MR-LINAC. Based on our initial experience, we developed a workflow for 1.5T MR-LINAC treatment of CNS tumors.
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Inmovilización , Imagen por Resonancia Magnética , Radioterapia Guiada por Imagen , Humanos , Masculino , Femenino , Radioterapia Guiada por Imagen/métodos , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Adulto , Estudios Retrospectivos , Anciano , Inmovilización/instrumentación , Inmovilización/métodos , Neoplasias del Sistema Nervioso Central/radioterapia , Neoplasias del Sistema Nervioso Central/diagnóstico por imagen , Planificación de la Radioterapia Asistida por Computador/métodos , Fantasmas de ImagenRESUMEN
Objective: The purpose of this study was to evaluate the positive impact of mobile neurofeedback (MNF) in neurotypical children compared to sham mobile neurofeedback. Methods: Neurotypical children aged 10-15 participated in the study. All subjects were assessed using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version Korean Version (K-SADS-PL-K) and confirmed to have no psychiatric symptoms. The participants were randomly assigned to the MNF active (N=31) or sham control (N=30) groups. The MNF program was administered using a mobile app for 30 min/day, 3 days/week, for 3 months. All participants and their parents completed self-report scales and participants complete neurocognitive function assessments including the continuous performance test, Stroop, children's color trails test-1 and 2, and intelligence test at baseline and after the 3-month MNF program. Results: This study involved 61 participants (mean [SD] age, 11.24 [1.84] years; 30 male participants [49.2%]). To verify the difference between the MNF group and the sham group, 2(MNF-Sham) X 2(Pre-Post) repeated measures ANOVA was performed. The main effect of the K-scale (Korea Internet addiction scale) between-group factor (MNF vs Sham) was not significant, but the main effect of the within-group factor (Pre vs Post) was significant (F=7.595, p=0.008). The interaction effect of between-group factors and within-group factors was also significant (F=5.979, p=0.017). In other self-reported scales of children and parents and neurocognitive function assessments, there was no significant difference between the two groups. Conclusion: Active mobile neurofeedback significantly improved children's K-scale score compared to the sham group. Therefore, mobile neurofeedback could be an easy-to-access therapeutic option for children at risk of Internet addiction. On the other hand, there was no significant difference in other scales and neurocognitive function. A 3-month intervention may not have been long enough to cause change, so longer interventions are needed for confirmation.
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PURPOSE: This study aimed to assess the feasibility and safety of administering intraoperative radiotherapy (IORT) as a boost during breast-conserving surgery (BCS) following neoadjuvant chemotherapy for patients at high risk of breast cancer recurrence. MATERIALS AND METHODS: Patients who underwent neoadjuvant chemotherapy received a single 20-Gy dose of IORT during BCS, followed by external beam radiotherapy 4-6 weeks after surgery. RESULTS: The median follow-up duration was 31.0 months (range, 18.0-59.0 months). Initial tumor sizes had a median of 2.6 cm (range: 0.8-5.3 cm), reducing to 0.3 cm (range: 0-4.0 cm) after neoadjuvant chemotherapy. The most common neoadjuvant chemotherapy regimen was doxorubicin and cyclophosphamide, followed by paclitaxel (n=42, 73.7%). Among 57 patients who received neoadjuvant chemotherapy before BCS and IORT, 2 patients (3.5%) required secondary surgery to achieve negative resection margins due to initially positive margins. Regional lymph node irradiation was performed in 37 (64.9%) patients. There was no grade 3 or higher adverse events, with 4 patients (7.0%) experiencing grade 2 acute radiation dermatitis and 3 (5.3%) having less than grade 2 breast edema. Binary correlation analysis did not reveal statistically significant associations between applicator size or radiation therapy modality and the risk of treatment-related toxicity. Furthermore, chi-square analysis showed that the grade of treatment-related toxicity was not associated with the fractionated regimen (p=0.375). CONCLUSION: Most patients successfully received IORT as a tumor bed boost after neoadjuvant chemotherapy. Thus, IORT may be a safe and feasible option for patients with advanced-stage breast cancer receiving neoadjuvant chemotherapy.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Terapia Neoadyuvante , Estudios de Factibilidad , Terapia Combinada , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Mastectomía Segmentaria , Dosificación RadioterapéuticaRESUMEN
The purpose of this study is to evaluate RadCalc, an independent dose verification software, for patient-specific quality assurance (PSQA) in online adaptive planning with a magnetic resonance linear accelerator (MR-linac) of a 1.5 T. Version 7.1.4 of RadCalc to introduce the capability to establish a beam model that incorporates MR field characteristics. A total of six models were established, with one using manufacturer-provided data and the others differing in percentage depth dose (PDD) data sources. Overall, two models utilized PDD data from the treatment planning system (TPS), and three used commissioned PDD data from gantry angles of 0° and 270°. Simple tests on a virtual water phantom assessed dose-calculation accuracy, revealing percentage differences ranging from -0.5% to -20.6%. Excluding models with significant differences, clinical tests on 575 adaptive plans (prostate, liver, and breast) showed percentage differences of -0.51%, 1.12%, and 4.10%, respectively. The doses calculated using RadCalc demonstrated similar trends to those of the PSQA-based measurements. The newly released version of RadCalc enables beam modeling that considers the characteristics of the 1.5 T magnetic field. The accuracy of the software in calculating doses at 1.5 T magnetic fields has been verified, thereby making it a reliable and effective tool for PSQA in adaptive plans.
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PURPOSE: The locally advanced unresectable intrahepatic cholangiocarcinoma (ICC) has detrimental oncological outcomes. In this study, we aimed to investigate the efficacy of radiotherapy in patients with locally advanced unresectable ICC. MATERIALS AND METHODS: Between 2001 and 2021, 116 patients were identified through medical record who underwent radiotherapy for locally advanced unresectable ICC. The resectability of ICC is determined by the multidisciplinary team at each institution. Overall survival (OS) were analyzed using the Kaplan-Meier method, and prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: The median equivalent radiotherapy dose in 2 Gy fractions (EQD2) was 52 Gy (range, 30 to 110 Gy). Forty-seven patients (40.5%) received sequential gemcitabine-cisplatin based chemotherapy (GEM-CIS CTx). Multivariate analysis identified two risk factors, EQD2 of ≥ 60 Gy and application of sequential GEM-CIS CTx for OS. Patients were grouped by these two risk factors: group 1, EQD2 ≥ 60 Gy with sequential GEM-CIS CTx (n=25); group 2, EQD2 < 60 Gy with sequential GEM-CIS CTx or fluoropyrimidine-based concurrent chemoradiotherapy (n=70); and group 3, radiotherapy alone (n=21). Curative resection was more frequently undergone in group 1 than in groups 2 or 3 (28% vs. 8.6% vs. 0%, respectively). Consequently, OS was significantly better in group 1 than in groups 2 and 3 (p < 0.05). CONCLUSION: Combined high-dose radiotherapy with sequential GEM-CIS CTx improved oncologic outcomes in patients with locally advanced unresectable ICC. Further prospective studies are required to validate these findings.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Quimioradioterapia , Colangiocarcinoma , Cisplatino , Desoxicitidina , Gemcitabina , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/mortalidad , Colangiocarcinoma/patología , Colangiocarcinoma/tratamiento farmacológico , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/patología , Adulto , Quimioradioterapia/métodos , Resultado del Tratamiento , Pronóstico , Anciano de 80 o más Años , Estudios Retrospectivos , Dosificación Radioterapéutica , Estimación de Kaplan-Meier , Estadificación de NeoplasiasRESUMEN
OBJECTIVE: We aim to explore the effects of transcranial direct current stimulation (tDCS) on food craving improvement and changes in brain function associated with craving by conducting a total of 10 sessions of tDCS over a period of 2 weeks on overweight and obese subjects. METHODS: A total of 15 patients who were overweight or obese (body mass index [BMI] ≥23 kg/m2) were included. Weight, BMI, neuropsychological variables, and food craving-related variables were assessed. We measured absolute and relative power in 19 channels and analyzed quantitative electroencephalography (qEEG) according to the following frequency ranges: delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-25 Hz), high beta (25-30 Hz), and gamma (30-80 Hz). RESULTS: After the application of tDCS, there was no significant reduction observed in weight and BMI. However, all measures related to food and eating showed a decrease in the intensity of cravings, and there was also a significant reduction in depression, anxiety, and perceived stress. In qEEG analysis, an increase in theta waves was observed in the left frontal area (F7 and F3), an increase in alpha waves in the right parietal area (P4), and a decrease in beta waves in the frontal area (FP2) and occipital area (O1). CONCLUSION: This study confirmed the beneficial effects of tDCS on food craving regulation in overweight or obese individuals and observed improved scores in psychological factors such as depression and anxiety. Furthermore, neurophysiological changes related to food craving were observed using qEEG.
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Immunocompromised patients with coronavirus disease 2019 were prospectively enrolled from March to November 2022 to understand the association between antibody responses and severe acute respiratory syndrome coronavirus 2 shedding. A total of 62 patients were analyzed, and the results indicated a faster decline in genomic and subgenomic viral RNA in patients with higher neutralizing and S1-specific immunoglobulin G (IgG) antibodies (both P < .001). Notably, high neutralizing antibody levels were associated with a significantly faster decrease in viable virus cultures (P = .04). Our observations suggest the role of neutralizing antibodies in prolonged virus shedding in immunocompromised patients, highlighting the potential benefits of enhancing their humoral immune response through vaccination or monoclonal antibody treatments.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19 , Huésped Inmunocomprometido , Inmunoglobulina G , SARS-CoV-2 , Esparcimiento de Virus , Humanos , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Estudios Prospectivos , Femenino , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Anciano , ARN Viral , Adulto , Formación de Anticuerpos/inmunologíaRESUMEN
Despite a high vaccination rate, the COVID-19 pandemic continues with immune-evading Omicron variants. The success of additional antigenic stimulation through breakthrough infection (BI) and updated vaccination in overcoming antigenic imprinting needs to be determined. Participants in a long-term follow-up cohort of healthcare worker (HCW) vaccinee were categorized according to their infection/vaccination status. Anti-SARS-CoV-2 spike/nucleocapsid protein antibodies were measured, and plaque reduction neutralization tests (PRNTs) against wild-type (WT), BA.5, BN.1, and XBB.1.5 were conducted. The neutralization activity of intravenous immunoglobulin (IVIG) products was evaluated to assess the immune status of the general population. Ninety-five HCWs were evaluated and categorized into seven groups. The WT PRNT ND50 value was highest regardless of infection/vaccination status, and groups with recent antigenic stimulation showed high PRNT titers overall. Groups with double Omicron stimulation, either by BI plus BA.4/5 bivalent vaccination or repeated BI, exhibited significantly higher BA.5 and BN.1 PRNT to WT PRNT ratios than those with single Omicron stimulation. Overall group immunity was estimated to be boosted in January 2023, reflecting the effect of the BA.4/5 bivalent booster and additional BIs, but slightly declined in June 2023. A substantial increase in the antibody concentrations of IVIG products was noticed in 2022, and recently produced IVIG products exhibited a substantial level of cross-reactive neutralizing activity against emerging variants. Neutralizing activity against emerging variants could be enhanced by repeated antigenic stimulation via BI and/or updated vaccination. Overall group immunity was elevated accordingly, and IVIG products showed substantial activity against circulating strains.
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Anticuerpos Neutralizantes , COVID-19 , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Infección Irruptiva , Pandemias , COVID-19/prevención & control , SARS-CoV-2 , Anticuerpos Antivirales , VacunaciónRESUMEN
There are limited data supporting current Centers for Disease Control and Prevention guidelines for the isolation period in moderate to severely immunocompromised patients with coronavirus disease 2019 (COVID-19). Adult COVID-19 patients who underwent solid organ transplantation (SOT) or received active chemotherapy against hematologic malignancy were enrolled and weekly respiratory samples were collected. Samples with positive genomic real-time polymerase chain reaction results underwent virus culture and rapid antigen testing (RAT). A total of 65 patients (40 with hematologic malignancy and 25 SOT) were enrolled. The median duration of viable virus shedding was 4 weeks (interquartile range: 3-7). Multivariable analysis revealed that B-cell depletion (hazard ratio [HR]: 4.76) was associated with prolonged viral shedding, and COVID-19 vaccination (≥3 doses) was negatively associated with prolonged viral shedding (HR: 0.22). The sensitivity, specificity, positive predictive value, and negative predictive value of RAT for viable virus shedding were 79%, 76%, 74%, and 81%, respectively. The negative predictive value of RAT was only 48% (95% confidence interval [CI]: 33-65) in the samples from those with symptom onset ≤20 days, but it was as high as 92% (95% CI: 85-96) in the samples from those with symptom onset >20 days. About half of immunocompromised COVID-19 patients shed viable virus for ≥4 weeks from the diagnosis, and virus shedding was prolonged especially in unvaccinated patients with B-cell-depleting therapy treatment. RAT beyond 20 days in immunocompromised patients had a relatively high negative predictive value for viable virus shedding.
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COVID-19 , Neoplasias Hematológicas , Adulto , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estudios Prospectivos , Vacunas contra la COVID-19 , Neoplasias Hematológicas/complicaciones , Esparcimiento de Virus , ARN Viral/análisisRESUMEN
Purpose: Intraoperative radiotherapy (IORT) can be used as a boost in combination with external whole breast irradiation. This study reports the clinical and dosimetric factors associated with IORT-related adverse events (AE). Methods and materials: Between 2014 and 2021, 654 patients underwent IORT. A single fraction of 20 Gy was prescribed to the surface of the tumour cavity using the mobile 50-kV X-ray source. For skin dose measurement, at least four optically stimulated luminescent dosimeter (OSLD) chips were annealed and attached to the skin edge in the superior, inferior, medial, and lateral locations during IORT. Logistic regression analyses were conducted to identify factors associated with IORT-related AE. Results: With a median follow-up period of 42 months, 7 patients experienced local recurrence, resulting in a 4-year local failure-free survival rate of 97.9%. The median skin dose measured by OSLD was 3.85 Gy (range, 0.67-10.89 Gy), and a skin dose of > 6 Gy was observed in 38 patients (2%). The most common AE was seroma (90 patients, 13.8%). We also found that 25 patients (3.9%) experienced fat necrosis during follow-up, and among them, 8 patients underwent biopsy or excision to exclude local recurrence. IORT-related late skin injury occurred in 14 patients, and a skin dose > 6 Gy was significantly associated with IORT-induced skin injury (odds ratio 4.942, 95% confidence interval 1.294-18.871, p = 0.019). Conclusions: IORT was safely administered as a boost to various populations of patients with breast cancer. However, several patients may experience severe skin injuries, and for older patients with diabetes, IORT should be performed with caution.
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Ongoing emergence of SARS-CoV-2 Omicron subvariants and their rapid worldwide spread pose a threat to public health. From November 2022 to February 2023, newly emerged Omicron subvariants, including BQ.1.1, BF.7, BA.5.2, XBB.1, XBB.1.5, and BN.1.9, became prevalent global strains (>5% global prevalence). These Omicron subvariants are resistant to several therapeutic antibodies. Thus, the antiviral activity of current drugs such as remdesivir, molnupiravir, and nirmatrelvir, which target highly conserved regions of SARS-CoV-2, against newly emerged Omicron subvariants need to be evaluated. We assessed the antiviral efficacy of the drugs using the half-maximal inhibitory concentration (IC50) against human isolates of 23 Omicron subvariants and four former SARS-CoV-2 variants of concern (VOCs) and compared it with the antiviral efficacy of these drugs against the SARS-CoV-2 reference strain (hCoV/Korea/KCDC03/2020). Maximal IC50-fold changes of remdesivir, molnupiravir, and nirmatrelvir were 1.9 (BA.2.75.2), 1.2 (B.1.627.2), and 1.4 (BA.2.3), respectively, compared to median IC50 values of the reference strain. Moreover, median IC50-fold changes of remdesivir, molnupiravir, and nirmatrelvir against the Omicron variants were 0.96, 0.4, and 0.62, respectively, similar to the 1.02, 0.88, and 0.67, respectively, median IC50-fold changes for previous VOCs. Although K90R and P132H in Nsp 5, and P323L, A529V, G671S, V405F, and ins823D in Nsp 12 mutations were identified, these amino acid substitutions did not affect drug antiviral activity. These results indicate that current antivirals retain antiviral efficacy against newly emerged Omicron subvariants. It is important to continue active surveillance and testing of new variants for drug resistance to enable early identification of drug-resistant strains.
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COVID-19 , Humanos , SARS-CoV-2 , Antivirales/farmacología , Lactamas , Leucina , NitrilosRESUMEN
PURPOSE: We used a new web application for rapid review of radiation therapy (RT) target volumes to evaluate the relationship between target delineation compliance with the international guidelines and outcomes of definitive RT for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The data set consisted of computed tomography simulation scans, RT structures, and clinical data of 354 patients with pathology-confirmed NPC treated with intensity modulated RT between 2005 and 2017. Target volumes were peer-reviewed in RT quality assurance rounds, and target contours were revised, if recommended, before treatment. We imported the contours of intermediate-risk clinical target volumes of the primary tumor (CTVp) of 332 patients into the application. Inclusion of anatomic sites within intermediate-risk CTVp was determined in accordance with 2018 international guidelines for CTV delineation for NPC and correlated with time to local failure (TTLF) using Cox regression. RESULTS: In the peer-review quality assurance analysis, local and distant control and overall survival rates were similar between peer-reviewed and nonreviewed cases and between cases with and without target contour changes. In the CTV compliance analysis, with a median follow-up of 5.6 years, 5-year TTLF and overall survival rates were 93.1% and 85.9%, respectively. The most frequently non-guideline-compliant anatomic sites were sphenoid sinus (n = 69, 20.8%), followed by cavernous sinus (n = 38, 19.3%), left and right petrous apices (n = 37 and 32, 11.1% and 9.6%), and clivus (n = 14, 4.2%). Among 23 patients with a local failure (6.9%), the number of noncompliant cases was 8 for sphenoid sinus, 7 cavernous sinus, 4 left and 3 right petrous apices, and 2 clivus. Cavernous sinus-conforming cases showed higher TTLF in comparison with nonconforming cases (93.6% vs 89.1%, P = .013). Multivariable analysis confirmed that cavernous sinus noncompliance was prognostic for TTLF. CONCLUSIONS: Our application allowed rapid quantitative review of CTVp in a large NPC cohort. Although compliance with the international guidelines was high, undercoverage of the cavernous sinus was correlated with TTLF.
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Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Humanos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , InternetRESUMEN
This study aimed to investigate the effectiveness of a quantitative electroencephalography (qEEG) biomarker in predicting the response to pharmacological treatment in patients with anxiety disorder. A total of 86 patients were diagnosed with anxiety disorder according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition, and subsequently treated with antidepressants. After 8-12 weeks, the participants were divided into treatment-resistant (TRS) and treatment-response (TRP) groups based on their Clinical Global Impressions-Severity (CGI-S) scores. We obtained the absolute-EEG measurements for 19-channels and analyzed qEEG findings according to the frequency range: delta, theta, alpha, and beta. The beta-wave was subdivided into low-beta, beta, and high-beta waves. The theta-beta ratio (TBR) was calculated, and an analysis of covariance was performed. Of the 86 patients with anxiety disorder, 56 patients (65%) were classified in the TRS group. The TRS and TRP groups did not differ in terms of age, sex, or medication-dosage. However, the baseline CGI-S was higher in the TRP group. After calibration by covariates, the TRP group showed higher beta-waves in T3 and T4, and a lower TBR, especially in T3 and T4, than the TRS group. These results indicate that patients with a lower TBR and higher beta and high-beta waves in T3 and T4 are more likely to respond to medication.
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Trastornos de Ansiedad , Gastrópodos , Humanos , Animales , Estudios Retrospectivos , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/tratamiento farmacológico , Electroencefalografía , Biomarcadores , CalibraciónRESUMEN
OBJECTIVE: Incontrovertible disease markers are absent in delirium. This study investigated the usefulness of quantitative electroencephalography (qEEG) in diagnosing delirium. METHODS: This retrospective case-control study reviewed medical records and qEEG data of 69 age/sex-matched patients (delirium group, n=30; control group, n=39). The first minute of artifact-free EEG data with eyes closed was selected. Nineteen electrodes' sensitivity, specificity, and correlation with delirium rating scale-revised-98 were analyzed. RESULTS: On comparing the means of absolute power by frontal, central, and posterior regions, the delta and theta powers showed significant differences (p<0.001) in all regions, and the magnitude of the absolute power was higher in the delirium group than in the control group; only the posterior region showed a significant (p<0.001) difference in beta power. The spectral power of theta at the frontal region (area under the curve [AUC]=0.84) and theta at the central and posterior regions (AUC=0.83) showed 90% sensitivity and 79% specificity, respectively, in differentiating delirious patients and controls. The beta power of the central region showed a significant negative correlation with delirium severity (R=-0.457, p=0.011). CONCLUSION: Power spectrum analysis of qEEG showed high accuracy in screening delirium among patients. The study suggests qEEG as a potential aid in diagnosing delirium.
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COVID-19 , Humanos , Estudios Prospectivos , Esparcimiento de Virus , Factores de Riesgo , Huésped Inmunocomprometido , ARN ViralRESUMEN
Introduction: We analyzed daily pre-treatment- (PRE) and real-time motion monitoring- (MM) MRI scans of patients receiving definitive prostate radiotherapy (RT) with 1.5 T MRI guidance to assess interfractional and intrafractional variability of the prostate and suggest optimal planning target volume (PTV) margin. Materials and methods: Rigid registration between PRE-MRI and planning CT images based on the pelvic bone and prostate anatomy were performed. Interfractional setup margin (SM) and interobserver variability (IO) were assessed by comparing the centroid values of prostate contours delineated on PRE-MRIs. MM-MRIs were used for internal margin (IM) assessment, and PTV margin was calculated using the van Herk formula. Results: We delineated 400 prostate contours on PRE-MRI images. SM was 0.57 ± 0.42, 2.45 ± 1.98, and 2.28 ± 2.08 mm in the left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively, after bone localization and 0.76 ± 0.57, 1.89 ± 1.60, and 2.02 ± 1.79 mm in the LR, AP, and SI directions, respectively, after prostate localization. IO was 1.06 ± 0.58, 2.32 ± 1.08, and 3.30 ± 1.85 mm in the LR, AP, and SI directions, respectively, after bone localization and 1.11 ± 0.55, 2.13 ± 1.07, and 3.53 ± 1.65 mm in the LR, AP, and SI directions, respectively, after prostate localization. Average IM was 2.12 ± 0.86, 2.24 ± 1.07, and 2.84 ± 0.88 mm in the LR, AP, and SI directions, respectively. Calculated PTV margin was 2.21, 5.16, and 5.40 mm in the LR, AP, and SI directions, respectively. Conclusions: Movements in the SI direction were the largest source of variability in definitive prostate RT, and interobserver variability was a non-negligible source of margin. The optimal PTV margin should also consider the internal margin.