ABSTRACT
Schistosomiasis is a neglected tropical disease with a significant socioeconomic impact. It is caused by several species of blood trematodes from the genus Schistosoma, with S. mansoni being the most prevalent. Praziquantel (PZQ) is the only drug available for treatment, but it is vulnerable to drug resistance and ineffective in the juvenile stage. Therefore, identifying new treatments is crucial. SmHDAC8 is a promising therapeutic target, and a new allosteric site was discovered, providing the opportunity for the identification of a new class of inhibitors. In this study, molecular docking was used to screen 13,257 phytochemicals from 80 Saudi medicinal plants for inhibitory activity on the SmHDAC8 allosteric site. Nine compounds with better docking scores than the reference were identified, and four of them (LTS0233470, LTS0020703, LTS0033093, and LTS0028823) exhibited promising results in ADMET analysis and molecular dynamics simulation. These compounds should be further explored experimentally as potential allosteric inhibitors of SmHDAC8.
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Metastatic epidural spinal cord compression develops in 5-10% of patients with cancer and is becoming more common as advancement in cancer treatment prolongs survival in patients with cancer (1-3). It represents an oncological emergency as metastatic epidural compression in adjacent neural structures, including the spinal cord and cauda equina, and exiting nerve roots may result in irreversible neurological deficits, pain, and spinal instability. Although management of metastatic epidural spinal cord compression remains palliative, early diagnosis and intervention may improve outcomes by preserving neurological function, stabilizing the vertebral column, and achieving localized tumor and pain control. Imaging serves an essential role in early diagnosis of metastatic epidural spinal cord compression, evaluation of the degree of spinal cord compression and extent of tumor burden, and preoperative planning. This review focuses on imaging features and techniques for diagnosing metastatic epidural spinal cord compression, differential diagnosis, and management guidelines.
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This research was initiated to assess and manage water quality status of fourteen surface drinking water intakes in El-Beheira Governorate, Egypt. The study was conducted on four main branches of water resources in the governorate. Three water quality indices (WQIs) and two multivariate statistical techniques were applied, based on the Egyptian guidelines for the Nile River. Water quality records were collected for two successive years, 2014 and 2015, and were analyzed by descriptive statistics. The results revealed the critical water quality status of the four branches at the fourteen intakes. The multivariate statistical techniques returned the critical water quality conditions to the agricultural drainage and the domestic wastewater discharges. In addition, a new software application was developed to manage WQIs calculation. An urgent water quality monitoring and assessment system should be initiated for the drinking water resources all over Egypt, based on the developed water quality assessment techniques of this study. PRACTITIONER POINTS: Three different WQIs and two different statistics tools were applied. Critical water quality status for the investigated surface drinking water intakes was reported. Agricultural drainage then domestic effluents are the main pollution sources. A new software application was developed to calculate WQIs to support decision makers.
Subject(s)
Environmental Monitoring , Water Quality , Egypt , Rivers , WastewaterABSTRACT
BACKGROUND: Here, we investigated radiological responses following chemotherapy alone as compared to both radiation/chemotherapy (chemoRT) in patients with thymic epithelial tumors (TETs) who did not receive upfront surgery. METHODS: TETs treated at a tertiary academic cancer center between January 2007 and July 2018 were identified. Patients received chemotherapy or chemoRT as initial therapy and pre- and post-treatment scans were available. Student's t-test, Wilcoxon rank-sum tests, and Cox proportional hazards method were used to compare clinical details and survival between groups. The primary outcome was change in tumor size, which was compared between groups using linear mixed-effects regression models, adjusting for baseline tumor size, age, and histology. RESULTS: A total of 24 of 114 patients with TETs identified met the inclusion criteria. The majority of patients had 67% thymoma (67%, n = 16) and AJCC8 III-IVA disease (58%, n = 14). Median age was 58.5 years (range: 33-76), median initial tumor volume was 187.1 cc (range: 28.7-653.6) and diameter was 8.5 cm (range: 4.5-14.3). Half of the patients received upfront chemotherapy (n = 12: 83% cisplatin/adriamycin/cyclophosphamide) or chemoRT (n = 12: 58% carboplatin/paclitaxel; median RT dose: 63 Gy [range: 60-70 Gy]). At a median imaging follow-up of 15 months (range: 0-86): ChemoRT was associated with increased average radiological response compared to chemotherapy alone (volume: -47.0 cc more, P < 0.001; diameter: -0.8 cm more, P = 0.03). In eight patients who received chemotherapy, 33% saw further tumor shrinkage (median volume: -42.3%, P = 0.03; diameter: -3.0%, P = 0.049) with additional radiation/chemoradiation. Median survival increased for patients ultimately receiving surgery versus those who did not (46 month, range: 16-127 vs. 14 month, range: 6-82; P < 0.01). CONCLUSIONS: ChemoRT produced a greater radiologic response compared to chemotherapy alone in patients with TETs not suitable for upfront resection. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We found that chemoRT was associated with a greater radiologic response compared to patients who received chemotherapy alone. WHAT THIS STUDY ADDS: What this study adds: In patients with TET not amenable to upfront resection, chemoRT may be a feasible strategy for cytoreduction.
Subject(s)
Chemoradiotherapy/methods , Neoplasms, Glandular and Epithelial/radiotherapy , Thymus Neoplasms/radiotherapy , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasms, Glandular and Epithelial/pathology , Thymus Neoplasms/pathologyABSTRACT
OBJECTIVE: To investigate the natural history of fibrotic lung disease in recipients of a single lung transplant for scleroderma-associated interstitial lung disease (ILD). METHODS: Global ILD (including ground glass, nodular opacities and fibrosis) was categorized into severity quintiles on first and last post-transplant CT scans, and percent fibrosis by manual contouring was also determined, in nine single lung transplant recipients. Quantitative mean lung densities and volumes for the native and allograft lungs were also acquired. RESULTS: In the native lung, global ILD severity quintile worsened in two cases and percent fibrosis worsened in four cases (range 5-28%). In the lung allograft, one case each developed mild, moderate and severe ILD; of these, new fibrotic ILD (involving <10% of lung) occurred in two cases and acute cellular rejection occurred in one. The average change in native lung density over time was +2.2 Hounsfield Units per year and lung volume +1.4 ml per year, whereas the allograft lung density changed by -5.5 Hounsfield Units per year and total volume +27 ml per year (P = 0.011 and P = 0.039 for native vs allograft density and volume comparisons, respectively). CONCLUSIONS: While the course of ILD in the native and transplanted lungs varied in this series, these cases illustrate that disease progression is common in the native lung, suggesting that either the immune process continues to target autoantigens or ongoing fibrotic pathways are active in the native lung. Mild lung disease may occur in the allograft after several years due to either allograft rejection or recurrent mild ILD.
Subject(s)
Allografts/diagnostic imaging , Graft Rejection/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Lung Transplantation/methods , Lung/diagnostic imaging , Pulmonary Fibrosis/diagnostic imaging , Scleroderma, Systemic/diagnostic imaging , Adult , Bronchiolitis Obliterans/diagnostic imaging , Bronchiolitis Obliterans/epidemiology , Disease Progression , Female , Graft Rejection/epidemiology , Humans , Longitudinal Studies , Lung Diseases, Interstitial/etiology , Lung Diseases, Interstitial/surgery , Lung Volume Measurements , Male , Middle Aged , Pulmonary Fibrosis/etiology , Pulmonary Fibrosis/surgery , Recurrence , Scleroderma, Systemic/complications , Tomography, X-Ray ComputedABSTRACT
PURPOSE: To evaluate the relationship between CT findings of diffuse lung disease and post-transcatheter aortic valve replacement (TAVR) outcomes. MATERIALS AND METHODS: Retrospective review of pre-TAVR CT scans obtained during 2012-2017 was conducted. Emphysema, reticulation, and honeycombing were separately scored using a five-point scale and applied to 10 images per examination. The fibrosis score was the sum of reticulation and honeycombing scores. Lung diseases were also assessed as dichotomous variables (zero vs nonzero scores). The two outcomes evaluated were death and the composite of death and readmission. RESULTS: The study included 373 patients with median age of 84 years (age range, 51-98 years; interquartile range, 79-88 years) and median follow-up of 333 days. Fibrosis and emphysema were present in 66 (17.7%) and 95 (25.5%) patients, respectively. Fibrosis as a dichotomous variable was independently associated with the composite of death and readmission (hazard ratio [HR], 1.54; P = .030). In those without known chronic lung disease (CLD) (HR, 3.09; P = .024) and those without airway obstruction, defined by a ratio of forced expiratory volume in 1 second to the forced vital capacity greater than or equal to 70% (HR, 1.67, P = .039), CT evidence of fibrosis was a powerful predictor of adverse events. Neither emphysema score nor emphysema as a dichotomous variable was an independent predictor of outcome. CONCLUSION: The presence of fibrosis on baseline CT scans was an independent predictor of adverse events after TAVR. In particular, fibrosis had improved predictive value in both patients without known CLD and patients without airway obstruction.Supplemental material is available for this article.© RSNA, 2020.
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Fungal pneumonias are increasingly common in the population of immunosuppressed patients. The diagnosis of fungal pneumonias represents a challenge for clinicians, and the morbidity and mortality of these infections are high in immunocompromised patients. CT findings may be nonspecific; however, in the appropriate clinical setting, they may suggest and even help establish the specific diagnosis. This article provides an overview about the CT findings and possible differential diagnosis of the most common pulmonary fungal infections.
Subject(s)
Aspergillosis/diagnostic imaging , Lung Diseases, Fungal/diagnostic imaging , Lung Diseases, Fungal/microbiology , Pneumonia/diagnostic imaging , Pneumonia/microbiology , Tomography, X-Ray Computed , Diagnosis, Differential , Humans , Immunocompromised Host , PrognosisABSTRACT
Purpose To test whether computer-aided diagnosis (CAD) approaches can increase the positive predictive value (PPV) and reduce the false-positive rate in lung cancer screening for small nodules compared with human reading by thoracic radiologists. Materials and Methods A matched case-control sample of low-dose computed tomography (CT) studies in 186 participants with 4-20-mm noncalcified lung nodules who underwent biopsy in the National Lung Screening Trial (NLST) was selected. Variables used for matching were age, sex, smoking status, chronic obstructive pulmonary disease status, body mass index, study year of the positive screening test, and screening results. Studies before lung biopsy were randomly split into a training set (70 cancers plus 70 benign controls) and a validation set (20 cancers plus 26 benign controls). Image features from within and outside dominant nodules were extracted. A CAD algorithm developed from the training set and a random forest classifier were applied to the validation set to predict biopsy outcomes. Receiver operating characteristic analysis was used to compare the prediction accuracy of CAD with the NLST investigator's diagnosis and readings from three experienced and board-certified thoracic radiologists who used contemporary clinical practice guidelines. Results In the validation cohort, the area under the receiver operating characteristic curve for CAD was 0.9154. By default, the sensitivity, specificity, and PPV of the NLST investigators were 1.00, 0.00, and 0.43, respectively. The sensitivity, specificity, PPV, and negative predictive value of CAD and the three radiologists' combined reading were 0.95, 0.88, 0.86, and 0.96 and 0.70, 0.69, 0.64, and 0.75, respectively. Conclusion CAD could increase PPV and reduce the false-positive rate in the early diagnosis of lung cancer. © RSNA, 2017 Online supplemental material is available for this article.
Subject(s)
Early Detection of Cancer/methods , Image Interpretation, Computer-Assisted/methods , Lung Neoplasms/diagnostic imaging , Multiple Pulmonary Nodules/diagnostic imaging , Tomography, X-Ray Computed/methods , Aged , Algorithms , Case-Control Studies , Female , Humans , Male , Middle Aged , Reproducibility of ResultsABSTRACT
RATIONALE AND OBJECTIVES: Noninfectious pulmonary complications are common among HIV-infected individuals and may be detected early by quantitative computed tomography (CT) scanning. The association of HIV disease markers with CT lung density measurement remains poorly understood. MATERIALS AND METHODS: One hundred twenty-five participants free of spirometry-defined lung disease were recruited from a longitudinal cohort study of HIV-infected and HIV-uninfected individuals to undergo standardized CT scan of the chest. Parenchymal density for the entire lung volume was calculated using computerized software. Qualitative assessment of CT scans was conducted by two radiologists masked to HIV status. Linear regression models were developed to determine the independent association of markers of HIV infection on inspiratory scan mean lung density (MLD). RESULTS: HIV-infected participants had a significantly higher MLD (denser lung) compared to HIV-uninfected participants (-815 Hounsfield unit [HU] vs -837 HU; P = 0.002). After adjusting for relevant covariates, HIV infection was independently associated with 19.9 HU higher MLD (95% CI 6.04 to 33.7 HU; P = 0.005). In qualitative assessment, only ground glass attenuation and cysts were noted more commonly among HIV-infected individuals compared to HIV-uninfected individuals (34% vs 17% [P = 0.045] and 27% vs 10% [P = 0.03], respectively). No qualitative radiographic abnormalities attenuated the association between HIV infection and increased MLD. CONCLUSIONS: HIV infection is independently associated with increased lung density. Although qualitative CT abnormalities were common in this cohort, only ground glass attenuation and cysts were noted more frequently in HIV-infected participants, suggesting that the increased lung density observed among HIV-infected individuals may be associated with subclinical inflammatory lung changes.
Subject(s)
HIV Infections/pathology , Lung Diseases/diagnostic imaging , Chronic Disease , Cohort Studies , Female , Forced Expiratory Volume/physiology , Humans , Longitudinal Studies , Lung/diagnostic imaging , Lung/pathology , Lung Diseases/pathology , Lung Diseases/physiopathology , Male , Middle Aged , Spirometry/methods , Tidal Volume/physiology , Tomography, X-Ray Computed/methods , Vital Capacity/physiologyABSTRACT
BACKGROUND: Many older patients with aortic stenosis are excluded from surgical intervention due to multiple comorbidities. For these patients, transcatheter aortic valve implantation (TAVI) is a viable treatment alternative. Cardiothoracic computed tomography (CT) provides detailed anatomic assessment of the aortic root structures for patient selection, preprocedural planning, and intraoperative decision-making; however, nonaortic incidental findings are frequently detected. The prevalence and clinical significance of these findings have not been well described. MATERIALS AND METHODS: This retrospective study examined incidental findings in 209 consecutive patients (96 women and 113 men; mean age, 70 y) with aortic stenosis undergoing preoperative cardiothoracic CT evaluation for TAVI during a 3-year period. Incidental findings were recorded, and medical records were reviewed for follow-up diagnostic examinations. RESULTS: Incidental findings, both significant and nonsignificant, were observed in 85.6% of patients (179/209). Noncalcified pulmonary nodules were the most common incidental finding occurring in 59/209 (28.2%) patients, followed by pleural effusion and emphysema both of which occurred in 34/209 (16.3%) patients, respectively. CONCLUSIONS: Cardiothoracic CT obtained for evaluation before TAVI has a high frequency of incidental findings.