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Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by antigen-specific T cells and antiplatelet autoantibodies that inhibit platelet production in the bone marrow or destroy platelets in the spleen. ITP is a form of autoimmunity and is closely associated with inflammation. Corticosteroids are the first-line therapy for ITP, with a total response rate of 53-80%. However, corticosteroid therapy is associated with significant side effects and is often ineffective in patients with corticosteroid-resistant or -intolerant disease. Eltrombopag has been validated as a second-line option in ITP therapy. Despite several studies demonstrating the efficacy and safety of Eltrombopag in immune thrombocytopenia patients, the prevalence of Eltrombopag-induced acute kidney injury has been observed. This case report describes a patient who experienced acute kidney injury during Eltrombopag therapy. A sudden increase in serum creatinine to 6.7 mg/dL and metabolic acidosis occurred after eight weeks of Eltrombopag. The patient's renal failure had worsened, proteinuria was detected, and emergency hemodialysis was initiated. With vigilant kidney function screening and prompt treatment, the patient's renal function improved remarkably following cessation of Eltrombopag and initiation of hemodialysis. This case highlights the importance of comprehensive medication history-taking and vigilant kidney function screening in patients receiving Eltrombopag.
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BACKGROUND: Primary immune thrombocytopenia (ITP) is an inflammatory autoimmune disease that can be managed with several treatment options. However, there is a lack of comparative data on the efficacy of these options in different phases of the disease. AIM OF THE STUDY: This study aimed to evaluate the efficacy of high-dose Dexamethasone (HD-DXM), Prednisolone + Azathioprine, Rituximab, Eltrombopag, and Romiplostim schedules in persistent, chronic refractory or relapsed Egyptian ITP patients with a platelet count ≤30 × 109/L. The primary outcome measure was a sustained increase in platelet counts over 50 × 109/L for an additional 12 months without additional ITP regimens. The study also aimed to identify a suitable treatment regimen with a long remission duration for each phase of ITP. RESULTS: Prednisolone + Azathioprine was significantly more effective in achieving an overall response in persistent patients than Romiplostim, high-dose Dexamethasone, and Rituximab. (90.9% vs. 66.6, [Odds ratio, OR: 5; confidence interval, CI 95% (0.866-28.86)], 45%, [OR: 0.082, CI 95% (0.015-0.448)] and, 25%, [OR: 30, CI 95% (4.24-211.8)], respectively, p-value < 0.01). Eltrombopag was significantly more effective in achieving a durable response in refractory ITP than HD-DXM, Rituximab, and Prednisolone; (80% compared to 32.2% [OR: 0.119, CI 95% (0.035-0.410)], 22.2% [OR:0.071, CI 95% (0.011-0.455)], and 18.1% [OR: 0.056, CI 95% (0.009-0.342)], respectively, p-value < 0.01). CONCLUSIONS: Finally, Eltrombopag following HD-DXM showed the highest percentage of patients with complete treatment-free survival times of at least 330 days. These findings could help clinicians choose the most appropriate treatment for their patients with ITP based on the phase of the disease. This trial is registered in clinicaltrials.gov with registration number NCT05861297.
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Adolescents increasingly find it difficult to picture their lives without social media. Practitioners need to be able to assess risk, and social media may be a new component to consider. Although there is limited empirical evidence to support the claim, the perception of the link between social media and mental health is heavily influenced by teenage and professional perspectives. Privacy concerns, cyberbullying, and bad effects on schooling and mental health are all risks associated with this population's usage of social media. However, ethical social media use can expand opportunities for connection and conversation, as well as boost self-esteem, promote health, and gain access to critical medical information. Despite mounting evidence of social media's negative effects on adolescent mental health, there is still a scarcity of empirical research on how teens comprehend social media, particularly as a body of wisdom, or how they might employ wider modern media discourses to express themselves. Youth use cell phones and other forms of media in large numbers, resulting in chronic sleep loss, which has a negative influence on cognitive ability, school performance, and socio-emotional functioning. According to data from several cross-sectional, longitudinal, and empirical research, smartphone and social media use among teenagers relates to an increase in mental distress, self-harming behaviors, and suicidality. Clinicians can work with young people and their families to reduce the hazards of social media and smartphone usage by using open, nonjudgmental, and developmentally appropriate tactics, including education and practical problem-solving.
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Immune thrombocytopenia (ITP) treatment has evolved recently. However, none of the treatments have only benefits without drawbacks. This study aimed to compare the clinical outcomes and adverse drug patterns of Eltrombopag, Romiplostim, Prednisolone + Azathioprine, High Dose-dexamethasone (HD-DXM) (control group), and Rituximab in primary ITP Egyptian patients. All patients were initiated with corticosteroids, HD-DXM, as a first-line treatment for the first month immediately following diagnosis. Four hundred sixty-seven ITP patients were randomly assigned to five groups. The outcome measures were judged at baseline, at the end of treatment (6 months), and after an additional 6-month free treatment period. The follow-up period for which relapse is noted was 6 months after the end of treatment. Eltrombopag and Romiplostim resulted in a significantly higher incidence of sustained response than Rituximab, HD-DXM, and Prednisolone + Azathioprine (55.2% and 50.6% vs. 29.2%, 29.1%, and 18%, respectively; p-value < 0.001). More patients on immunomodulators (Prednisolone+ Azathioprine, HD-DXM, and Rituximab) relapsed than those on Romiplostim and Eltrombopag (81.9%, 70.8%, and 70.7% vs. 49.3%, and 44.7%, respectively; p-value < 0.01). We also describe 23 reports of pulmonary hypertension with Prednisolone+ Azathioprine and 13 reports with HD-DXM. The thrombotic events occurred in 16.6% and 13% of patients who received Eltrombopag and Romiplostim treatment, respectively. Most patients had at least one or two risk factors (92.8% of cases). Corticosteroids are effective first-line therapy in primary ITP patients. However, relapse is frequent. Eltrombopag and Romiplostim are safer and more effective than Prednisolone, HD-DXM, and Rituximab. They might be reasonable beneficial options after a one-month HD-DXM regimen.
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Introduction Hypertension (HTN) is one of the most important cardiovascular risk factors. It is associated with significant complications, such as coronary artery disease, stroke, and chronic kidney disease. Awareness among hypertensive patients regarding their blood pressure (BP) is low in the Kingdom of Saudi Arabia. Aim This study aimed to evaluate the awareness of patients regarding their BP readings and to identify which aspects of HTN they needed to be informed about. Patients and methods A descriptive cross-sectional study was conducted among hypertensive patients attending outpatient clinics at King Fahad Medical City, Riyadh, Saudi Arabia. An electronic questionnaire was used by a trained physician to collect data from patients during telephone interviews. The information included socio-demographic data (i.e., age, gender, and education), family history, compliance with medications, and BP measurements. Patients were asked to answer questions to assess their awareness of their BP readings. Results Of the 475 hypertensive patients included in this study, 32.7% were aged between 56 and 65 years and 60.4% were female. The proportion of patients who had knowledge of their target BP (systolic: 120-129 mmHg; diastolic: 80-84 mmHg) was 74.4%. The significant independent predictors of increased knowledge about BP were a high level of education, regular measurement of BP, and having received education about a healthy lifestyle. The significant independent predictor of decreased knowledge about BP was having an acceptable or poor understanding of chronic BP. Conclusion Hypertensive patients visiting the outpatient clinic at King Fahad Hospital had a good understanding of their target BP readings. Educated patients who regularly measured their BP and who received education about a healthy lifestyle tended to exhibit a higher motivation to achieve their BP targets. More research is needed to gain more insights into the knowledge of hypertensive patients and into how they manage their BP to determine the factors that influence their knowledge.
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Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic/adverse effects , Chemoembolization, Therapeutic/methods , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Treatment OutcomeABSTRACT
BACKGROUND: Routine computed tomography (CT) scans are thought to have poor performance for detection of gastrointestinal (GI) neuroendocrine neoplasms (NENs), which leads to delayed workup. Detection of even 1 bowel tumor can guide diagnostic workup and management. The purposes of this study were to assess the accuracy of multidetector computed tomography (MDCT) and to compare negative versus positive enteric contrast in detecting at least 1 GI tumor per patient with suspected or confirmed diagnosis of a NEN. METHODS: This retrospective study included 107 patients with intravenous and oral contrast (65 positive, 40 negative, and 2 no oral contrast) abdominopelvic MDCT. Two abdominal radiologists independently analyzed the CTs for detection and localization of bowel NENs. Surgical pathology was considered the reference standard. Analyses included κ and summary statistics, McNemar test, Pearson χ2 test, and Fisher exact test. RESULTS: Among the 107 CT scans, there were 30 pathology negative studies and 77 studies with positive pathology for GI NEN. Interreader agreement for CT evaluation was substantial (κ = 0.61). At least 1 GI NEN per patient was detected with 51% to 53% sensitivity, 87% to 93% specificity, 91% to 95% positive predictive value (PPV), 42% negative predictive value, and 63% accuracy for each reader, and 57% accuracy when only the concordant (ie, matching) results of the 2 readers were considered. Computed tomography scans with negative enteric contrast had significantly higher sensitivity for concordant results than CTs with positive enteric contrast (58% vs 30%, P = 0.01). Specificity (100% vs 95%, P = 0.5), PPV (100% vs 93%, P = 0.49), negative predictive value (39% vs 39%, P = 0.99), and accuracy (67% vs 51%, P = 0.10) were not significantly different for negative versus positive enteric contrast for the concordant results. There was no significant difference in GI NEN localization between the readers. CONCLUSIONS: Routine MDCT with either positive or negative enteric contrast can detect at least 1 GI tumor per patient with more than 90% PPV and more than 50% accuracy in patients suspected of GI NEN. Using negative enteric contrast improves sensitivity for GI NEN versus positive enteric contrast. In addition, there is high accuracy in localizing the bowel tumor with positive or negative enteric contrast, which may guide surgery. Radiologists should have heightened awareness that evaluating such scans closely may lead to detection of primary bowel NENs at a higher rate than previously reported.
Subject(s)
Multidetector Computed Tomography , Neuroendocrine Tumors , Contrast Media , Humans , Intestine, Small/pathology , Multidetector Computed Tomography/methods , Neuroendocrine Tumors/diagnostic imaging , Neuroendocrine Tumors/pathology , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Brucella infection in animals is considered a great problem in most countries of the world. Our study designed to determine the prevalence of brucella in field animal's milk in Dhamar governorate, Yemen. Total of 808 raw milk samples from non-aborted field animals, 120 milk samples from aborted animals, and 30 pasteurized milk samples were teste by Milk-Ring Test (MRT), milk-ELISA test, isolation and identification of brucella species, and antibiotic susceptibility. The prevalence of brucella in milk samples from field animals was 0.8%, 2.6%, and 2% in cows, sheep, and goat milk samples respectively with MRT, and 0.8%, 1.3% and 1.6% in cows, sheep and goat milk samples respectively with the milk- ELISA test. The prevalence rate in milk samples from aborted animals was 33%, 64% and 41.2% with the MRT and 39%, 49%, and 41.2% in cows, sheep and goats respectively with the milk-ELISA test. All pasteurized milk samples were negative for the milk-ELISA test. The result of isolation showed 0.1% of Brucella in milk samples from field animals while 9.2% from aborted animals. All isolates of Brucella species were sensitivities to rifampicin, doxycycline, kanamycin, gentamicin, streptomycin, tetracycline, and ciprofloxacin, while resistant to ampicillin, erythromycin, and novobiocin. In conclusion, the high prevalence of milk brucella especially in aborted animals needs focusing and build controlling strategies plans to decrease the losses to the economy and avoid transferred to humans with unpasteurized milk consumption.
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AIMS: To estimate if chronic anticoagulant (CAC) treatment is associated with morbidity and mortality outcomes of patients hospitalized for SARS-CoV-2 infection. METHODS: In this European multicentric cohort study, we included 1186 patients of whom 144 were on CAC (12.1%) with positive coronavirus disease 2019 testing between 1 February and 30 July 2020. The average treatment effect (ATE) analysis with a propensity score-matching (PSM) algorithm was used to estimate the impact of CAC on the primary outcomes defined as in-hospital death, major and minor bleeding events, cardiovascular complications (CCI), and acute kidney injury (AKI). We also investigated if different dosages of in-hospital heparin were associated with in-hospital survival. RESULTS: In unadjusted populations, primary outcomes were significantly higher among CAC patients compared with non-CAC patients: all-cause death (35% vs. 18% Pâ<â0.001), major and minor bleeding (14% vs. 8% Pâ=â0.026; 25% vs. 17% Pâ=â0.014), CCI (27% vs. 14% Pâ<â0.001), and AKI (42% vs. 19% Pâ<â0.001). In ATE analysis with PSM, there was no significant association between CAC and primary outcomes except for an increased incidence of AKI (ATE +10.2%, 95% confidence interval 0.3-20.1%, Pâ=â0.044). Conversely, in-hospital heparin, regardless of dose, was associated with a significantly higher survival compared with no anticoagulation. CONCLUSIONS: The use of CAC was not associated with the primary outcomes except for the increase in AKI. However, in the adjusted survival analysis, any dose of in-hospital anticoagulation was associated with significantly higher survival compared with no anticoagulation.
Subject(s)
Acute Kidney Injury , COVID-19 , Acute Kidney Injury/chemically induced , Acute Kidney Injury/epidemiology , Anticoagulants/adverse effects , COVID-19/complications , COVID-19 Testing , Cohort Studies , Hospital Mortality , Hospitals , Humans , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
BACKGROUND. Multiple commercial and open-source software applications are available for texture analysis. Nonstandard techniques can cause undesirable variability that impedes result reproducibility and limits clinical utility. OBJECTIVE. The purpose of this study is to measure agreement of texture metrics extracted by six software packages. METHODS. This retrospective study included 40 renal cell carcinomas with contrast-enhanced CT from The Cancer Genome Atlas and Imaging Archive. Images were analyzed by seven readers at six sites. Each reader used one of six software packages to extract commonly studied texture features. Inter- and intrareader agreement for segmentation was assessed with intraclass correlation coefficients (ICCs). First-order (available in six packages) and second-order (available in three packages) texture features were compared between software pairs using Pearson correlation. RESULTS. Inter- and intrareader agreement was excellent (ICC, 0.93-1). First-order feature correlations were strong (r ≥ 0.8, p < .001) between 75% (21/28) of software pairs for mean intensity and SD, 48% (10/21) for entropy, 29% (8/28) for skewness, and 25% (7/28) for kurtosis. Of 15 second-order features, only cooccurrence matrix correlation, gray-level nonuniformity, and run-length nonuniformity showed strong correlation between software packages (r = 0.90-1, p < .001). CONCLUSION. Variability in first- and second-order texture features was common across software configurations and produced inconsistent results. Standardized algorithms and reporting methods are needed before texture data can be reliably used for clinical applications. CLINICAL IMPACT. It is important to be aware of variability related to texture software processing and configuration when reporting and comparing outputs.
Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Image Processing, Computer-Assisted/methods , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Software , Tomography, X-Ray Computed , Aged , Female , Humans , Image Processing, Computer-Assisted/standards , Male , Middle Aged , Observer Variation , Reproducibility of Results , Software/standardsABSTRACT
OBJECTIVE: The repurposing of nitazoxanide, doxycycline and azithromycin may be effective to improve the symptoms in mild and moderate COVID-19 subjects. This study aimed to detect and explain the efficacy of reusing of these drugs in treating COVID-19. METHODS: The study was divided into two parts: clinical and computational parts. In the clinical part, 80 (30 females) subjects with reverse transcription-polymerase chain reaction-confirmed COVID-19 with mild and moderate symptoms were enrolled in the study. Subjects were treated with azithromycin or doxycycline, and nitazoxanide was added to the treatment if the subject had diarrhoea. Subjects were divided into four groups: Group 1: subjects treated with azithromycin (20 subjects); Group 2: subjects treated with doxycycline (20 subjects); Group 3: subjects treated with a combination of nitazoxanide and doxycycline (20 subjects); and Group 4: subjects treated with a combination of nitazoxanide and azithromycin (20 subjects). In the computational part, we docked the three drugs against all currently available COVID-19-related protein targets (viral and non-viral). Subsequently, top hits were subjected to molecular dynamic simulations (MDSs) (50 ns) and binding free energy calculations to further validate the docking experiments and to investigate the binding modes of the potential inhibitors. RESULTS: The symptomatic improvement of mild to moderate subjects was seen on the fifth day after starting treatment in Group 3 and Group 4 and on the seventh day in Group 2. However, for Group 1, the symptomatic improvement of mild to moderate subjects was not seen on the fifth day and required replacement by doxycycline to get the symptomatic improvement. None of the subjects needed intensive care admission and no deaths were reported. In silico, results were in good accordance with the clinical outcomes, where both nitazoxanide and doxycycline achieved the best docking scores against the viral ADP-ribose phosphatase (ADPRP) and the human Adaptor-Associated Kinase 1 (AAK1). MDSs revealed that both drugs were stable in their bindings indicating that they can be considered as lead molecules for targeting ADPRP and AAK1. CONCLUSION: The clinical and computational studies applied on three FDA-approved antimicrobials together with their recent clinical findings revealed that both nitazoxanide and doxycycline have great therapeutic potential against COVID-19. The future in vitro mechanistic investigation may confirm our primary computational outcomes, and in turn, these classes of compounds provide a promising starting point for further anti-COVID-19 therapeutics.
Subject(s)
COVID-19 Drug Treatment , Drug Repositioning , Pharmaceutical Preparations , Adolescent , Computer Simulation , Female , Humans , Lactation , Male , SARS-CoV-2ABSTRACT
Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy and the leading cause of death in patients with cirrhosis. Various treatments for HCC are available, including transarterial chemoembolization (TACE), which is the commonest intervention performed in HCC. Radiologic tumor response following TACE is an important prognostic factor for patients with HCC. We hypothesized that, for large HCC tumors, assessment of treatment response made with automated volumetric response evaluation criteria in solid tumors (RECIST) might correlate with the assessment made with the more time- and labor-intensive unidimensional modified RECIST (mRECIST) and manual volumetric RECIST (M-vRECIST) criteria. Accordingly, we undertook this retrospective study to compare automated volumetric RECIST (A-vRECIST) with M-vRECIST and mRESIST for the assessment of large HCC tumors' responses to TACE. Methods:We selected 42 pairs of contrast-enhanced computed tomography (CT) images of large HCCs. Images were taken before and after TACE, and in each of the images, the HCC was segmented using both a manual contouring tool and a convolutional neural network. Three experienced radiologists assessed tumor response to TACE using mRECIST criteria. The intra-class correlation coefficient was used to assess inter-reader reliability in the mRECIST measurements, while the Pearson correlation coefficient was used to assess correlation between the volumetric and mRECIST measurements. Results:Volumetric tumor assessment using automated and manual segmentation tools showed good correlation with mRECIST measurements. For A-vRECIST and M-vRECIST, respectively, r = 0.597 vs. 0.622 in the baseline studies; 0.648 vs. 0.748 in the follow-up studies; and 0.774 vs. 0.766 in the response assessment (P < 0.001 for all). The A-vRECIST evaluation showed high correlation with the M-vRECIST evaluation (r = 0.967, 0.937, and 0.826 in baseline studies, follow-up studies, and response assessment, respectively, P < 0.001 for all). Conclusion:Volumetric RECIST measurements are likely to provide an early marker for TACE monitoring, and automated measurements made with a convolutional neural network may be good substitutes for manual volumetric measurements.
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PURPOSE: The aims of the study were to assess the typical and atypical radiologic features of pathologically proven adrenal adenomas and to determine the relationship between the radiologic and histopathologic classification. METHODS: We retrospectively studied 156 pathologically proven adrenal adenomas in 154 patients from our institutional databases who have computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations before intervention. We determined the histopathologic diagnosis (typical or atypical) using Weiss scoring and classified the adenomas radiologically into typical, atypical, or indeterminate based on lesion size, precontrast CT attenuation, absolute percentage washout, calcification, and necrosis. The κ statistic was used to assess the agreement between radiologists. The Fisher exact test was used to compare the radiologic and pathological classifications. RESULTS: In consensus, there were 83 typical, 42 atypical, and 31 indeterminate adrenal lesions. Logistic regression model showed that radiologically atypical adenoma was significantly associated with larger size, lobulated shape, higher unenhanced CT attenuation, heterogeneous appearance, nonfunctioning status, absolute percentage washout of less than 60%, and a signal intensity index of less than 16.5%.Pathologically, 147 adenomas were pathologically typical (Weiss 0), and 9 adenomas were pathologically atypical (Weiss 1-2). Radiologically, there was substantial agreement between both readers, with Cohen κ at 0.71. Approximately 98% of radiologically typical adenomas were pathologically typical. Only 17% of radiologically atypical adenomas were pathologically atypical. All radiologically indeterminate adenomas were pathologically typical. However, some of the radiologically indeterminate and typical adenomas still had an atypical component on pathologic analysis, such as necrosis, nuclear atypia, or oncocytic features. CONCLUSIONS: Radiologically atypical lesion was significantly associated with larger size and higher unenhanced CT attenuation. Approximately 27% of the cases demonstrated atypical features on imaging. Most radiologically atypical adrenal adenomas are pathologically typical.
Subject(s)
Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/pathology , Preoperative Care/methods , Tomography, X-Ray Computed/methods , Adenoma/diagnostic imaging , Adenoma/pathology , Adolescent , Adrenal Gland Neoplasms/surgery , Adrenal Glands/diagnostic imaging , Adrenal Glands/pathology , Adrenal Glands/surgery , Adult , Aged , Aged, 80 and over , Child , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Retrospective Studies , Young AdultABSTRACT
PURPOSE: Some patients with hepatocellular carcinoma (HCC) are more likely to experience disease progression despite transcatheter arterial chemoembolization (TACE) treatment, and thus would benefit from early switching to other therapeutic regimens. We sought to evaluate a fully automated machine learning algorithm that uses pre-therapeutic quantitative computed tomography (CT) image features and clinical factors to predict HCC response to TACE. MATERIALS AND METHODS: Outcome information from 105 patients receiving first-line treatment with TACE was evaluated retrospectively. The primary clinical endpoint was time to progression (TTP) based on follow-up CT radiological criteria (mRECIST). A 14-week cutoff was used to classify patients as TACE-susceptible (TTP ≥14 weeks) or TACE-refractory (TTP <14 weeks). Response to TACE was predicted using a random forest classifier with the Barcelona Clinic Liver Cancer (BCLC) stage and quantitative image features as input as well as the BCLC stage alone as a control. RESULTS: The model's response prediction accuracy rate was 74.2% (95% CI=64%-82%) using a combination of the BCLC stage plus quantitative image features versus 62.9% (95% CI= 52%-72%) using the BCLC stage alone. Shape image features of the tumor and background liver were the dominant features correlated to the TTP as selected by the Boruta method and were used to predict the outcome. CONCLUSION: This preliminary study demonstrates that quantitative image features obtained prior to therapy can improve the accuracy of predicting response of HCC to TACE. This approach is likely to provide useful information for aiding HCC patient selection for TACE.
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Hepatocellular carcinoma (HCC) is one of the most common primary hepatic malignancies and one of the fastest-growing causes of cancer-related mortality in the United States. The molecular basis of HCC carcinogenesis has not been clearly identified. Among the molecular signaling pathways implicated in the pathogenesis of HCC, the Wnt/ß-catenin signaling pathway is one of the most frequently activated. A great effort is under way to clearly understand the role of this pathway in the pathogenesis of HCC and its role in the transition from chronic liver diseases, including viral hepatitis, to hepatocellular adenomas (HCAs) and HCCs and its targetability in novel therapies. In this article, we review the role of the ß-catenin pathway in hepatocarcinogenesis and progression from chronic inflammation to HCC, the novel potential treatments targeting the pathway and its prognostic role in HCC patients, as well as the imaging features of HCC and their association with aberrant activation of the pathway.
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OBJECTIVES: To determine whether the qualitative sonographic appearance of slow deep venous flow in the lower extremities correlates with quantitative slow flow and an increased risk of deep venous thrombosis (DVT) in oncology patients. METHODS: In this Institutional Review Board-approved retrospective study, we reviewed lower extremity venous Doppler sonographic examinations of 975 consecutive patients: 482 with slow flow and 493 with normal flow. The subjective slow venous flow and absence of initial DVT were confirmed by 2 radiologists. Peak velocities were recorded at 3 levels. Each patient was followed for DVT development. The associations between DVT and the presence of slow venous flow were examined by the Fisher exact test; a 2-sample t test was used for peak velocity and DVT group comparisons. The optimal cutoff peak velocity for correlation with the radiologists' perceived slow flow was determined by the Youden index. RESULTS: Deep venous thrombosis development in the slow-flow group (21 of 482 [4.36%]) was almost doubled compared with patients who had normal flow (11 of 493 [2.23%]; P = .0456). Measured peak venous velocities were lower in the slow-venous flow group (P < .001). Patients with subsequent DVT did not have a significant difference in venous velocities compared with their respective patient groups. The sum of 3 venous level velocities resulted in the best cutoff for dichotomizing groups into normal versus slow venous flow. CONCLUSIONS: Qualitative slow venous flow in the lower extremities on Doppler sonography accurately correlates with quantitatively slower flow, and this preliminary evaluation suggests an associated mildly increased rate of subsequent DVT development in oncology patients.
Subject(s)
Lower Extremity/blood supply , Tertiary Care Centers , Ultrasonography, Doppler/methods , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/physiopathology , Blood Flow Velocity/physiology , Evaluation Studies as Topic , Female , Humans , Lower Extremity/physiopathology , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Tertiary Healthcare/methodsABSTRACT
BACKGROUND Toxoplasmosis is an uncommon but potentially fatal complication following allogeneic hematopoietic stem cell transplantation (HCT). Post-transplant toxoplasmosis is often a reactivation of prior infection and typically occurs within the first 6 months of transplant. Herein, we report that cerebral toxoplasmosis may occur 22 months after allogeneic hematopoietic stem cell transplantation. CASE REPORT We describe a case of cerebral toxoplasmosis that occurred 22 months after an allogeneic HCT while the patient was on aerosolized pentamidine for Pneumocystis jiroveci pneumonia (PCP) prophylaxis. The disease was only diagnosed after brain biopsy because of atypical MRI appearance of the cerebral lesion and negative Toxoplasma gondii IgG antibody test result in the cerebrospinal fluid (CSF). The patient received pyrimethamine and sulfadiazine treatment, with dramatic improvement after several months. The patient is alive 2 years after infection diagnosis, with no evidence of disease and is off Toxoplasma prophylaxis. CONCLUSIONS Cerebral toxoplasmosis can occur late after allogeneic HCT while patients are on immunosuppression therapy, with atypical features on imaging studies and negative Toxoplasma gondii IgG antibody test result in the CSF. Pre-transplant serologic screening for T. gondii antibodies in allogeneic transplant candidates is warranted. Brain biopsy can be a helpful diagnostic tool for cerebral lesions.