Prostate cancer (PCa) is the most commonly diagnosed visceral cancer in men and is responsible for the second highest cancer-related male mortality rate in Western countries, with increasing rates being reported in Korea, Japan, and China. Considering the low sensitivity of prostate-specific antigen (PSA) testing, it is widely agreed that reliable, age-independent markers of the presence, nature, and progression of PCa are required to facilitate diagnosis and timely treatment. Metabolomics or metabonomics has recently emerged as a novel method of PCa detection owing to its ability to monitor changes in the metabolic signature, within biofluids or tissue, that reflect changes in phenotype and function. This review outlines the physiology of prostate tissue and prostatic fluid in health and in malignancy in relation to metabolomics as well as the principles underlying the methods of metabolomic quantification. Promising metabolites, metabolic profiles, and their correlation with the presence and stage of PCa are summarized. Application of metabolomics to biofluids and in vivo quantification as well as the direction of current research in supplementing and improving current methods of detection are discussed. The current debate in the urology literature on sarcosine as a potential biomarker for PCa is reviewed and discussed. Metabolomics promises to be a valuable tool in the early detection of PCa that may enable earlier treatment and improved clinical outcomes.
Biomarkers ; China ; Humans ; Japan ; Korea ; Male ; Metabolome ; Metabolomics ; Organothiophosphorus Compounds ; Passive Cutaneous Anaphylaxis ; Phenotype ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Sarcosine ; Urology

BACKGROUND/AIMS: It has been shown that the drug-eluting beads loaded with doxorubicin (DEBDOX) are effective for the treatment of hepatocellular carcinoma (HCC). However, the optimal safety and efficacy still remain to be established by using various bead sizes, doxorubicin doses, and the degree of stasis.The aim of this study was to determine the optimal safety and efficacy of DEBDOX in the treatment of HCC. METHODS: Analysis of a 503-patient prospective, multicenter, multinational Bead Registry Database from 2007 to 2010 identified 206 patients who had been treated for HCC with DEBDOX. Primary endpoints were to compare safety, tolerance, response rates, and overall survival based on bead size (100-300, 300-500, 500-700, and 700-900 microm), number of vials, doxorubicin dose, and degree of stasis. RESULTS: In total, 206 patients underwent 343 treatments. The use of all four bead sizes was similar based on Child-Pugh class and Okuda stage, with a significantly higher use (50%) of beads of size 100-300 microm in patients with portal vein thrombosis (P=0.05). Significant differences were seen for the number of median treatments, median doxorubicin dose, lobar infusion), and degree of complete stasis. The rate of adverse events was higher for larger beads than for smaller beads (28% vs. 16%; P=0.02). CONCLUSIONS: Bead size and dose may vary according to disease distribution. Smaller beads offer the opportunity for repeated treatments, a larger cumulative dose delivery, a lesser degree of complete stasis, and fewer adverse events.
Adult ; Aged ; Aged, 80 and over ; Antibiotics, Antineoplastic/*administration & dosage/adverse effects ; Carcinoma, Hepatocellular/*drug therapy/mortality ; Dose-Response Relationship, Drug ; Doxorubicin/*administration & dosage/adverse effects ; Drug Carriers/*chemistry ; Female ; Humans ; Liver Neoplasms/*drug therapy/mortality ; Male ; Middle Aged ; Particle Size ; Prospective Studies ; Severity of Illness Index

Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo.

Objective: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. Methods The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician’s clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible.Trial registration ClinicalTrials.gov Identifier NCT00880802

Objective: The present study investigated, whether computer-aided therapy in patients with Parkinson’s disease is equivalent/non-inferior to conventional Lee Silvermann Voice Treatment (LSVT)-BIGtherapy in respect to motor outcome as measured by the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS-III) and quality of life as measured by the Parkinson’s Disease Questionnaire (PDQ-39). Methods: In this controlled, rater-blinded study, 34 patients were included and 24 patients randomized to train seven standard exercises of the BIG-therapy either by a computer (BeBIG-group) or by a certified LSVT-BIG therapist (ThBIG-group) over four weeks. Equivalence was assessed by comparing the confidence interval of the BeBIG-group to the equivalence margin of the ThBIG-group. Results: There were no significant group differences in respect to age, disease duration, L-dopa equivalent daily dose or clinical stage of the disease. Both groups profited significantly from the therapy as demonstrated by an improvement in the MDS-UPDRS-III of 9.17 point in the BeBIG-group and of 8.92 points in the ThBIG-group. There was a non-significant decrease in the PDQ-39 of 9.23 points in the BeBIG-group and 4.23 points in the ThBIG-group. However, equivalence could not be demonstrated as the improvement of the BeBIG-group exceeded the confidence interval of the ThBIG-group. Conclusion: Physical training by a computer as well as by a therapist improves motor symptoms and quality of life in Parkinson’s disease. Both therapies are not equivalent, superiority of the computerized training can however not be concluded, as the study was only designed to test for non-inferiority. Therefore, computerized training can be considered as an add-on-therapy

Epigenetic changes are potentially important for the ontogeny and progression of tumors but are not usually studied because of the complexity of analyzing transcript regulation resulting from epigenetic alterations. Prostate cancer (PCa) is characterized by variable clinical manifestations and frequently unpredictable outcomes. We performed an expression quantitative trait loci (eQTL) analysis to identify the genomic regions that regulate gene expression in PCa and identified a relationship between DNA methylation and clinical information. Using multi-level information published in The Cancer Genome Atlas, we performed eQTL-based analyses on DNA methylation and gene expression. To better interpret these data, we correlated loci and clinical indexes to identify the important loci for both PCa development and progression. Our data demonstrated that although only a small proportion of genes are regulated via DNA methylation in PCa, these genes are enriched in important cancer-related groups. In addition, single nucleotide polymorphism analysis identified the locations of CpG sites and genes within at-risk loci, including the 19q13.2-q13.43 and 16q22.2-q23.1 loci. Further, an epigenetic association study of clinical indexes detected risk loci and pyrosequencing for site validation. Although DNA methylation-regulated genes across PCa samples are a small proportion, the associated genes play important roles in PCa carcinogenesis.

OBJECTIVE

To describe the treatment outcomes of patients who underwent tube pericardiostomy for all etiologies of non-traumatic massive pericardial effusion or tamponade during the COVID-19 pandemic and determine the association between patient profile and treatment outcomes.

Data were obtained from patients with massive pericardial effusion or cardiac tamponade who underwent surgical drainage from January 1, 2020, to September 1, 2022, in the University of the Philippines – Philippine General Hospital (UP-PGH). These patients’ demographic and clinical profiles, and treatment outcomes were evaluated using frequencies and percentages. Chi-squared and Fisher’s tests determined the differences between COVID (+) and (-) groups. Odds Ratio was used to assess the risk of complications and mortality.

The study population comprised 90 patients with a mean age of 45 years. 54.4% were females. Fifteen (16.67%) were COVID-19 (+) and 75 (83.33%) were COVID-19 (-). Most of the patients were of O+ blood type (34.4%), with no smoking history (67.8%) and no COVID-19 vaccination (76.7%). Common comorbidities were cancer (70%), tuberculosis infection (32.2%), and hypertension (25.6%). No significant difference was found between the two study groups. The presentation was subacute (one week to three months) (62.2%), with the most common symptoms of dyspnea (81.1%), orthopnea (61.1%), and cough (52.2%). Tachycardia (80%) and tachypnea (57.8%) were the most common presenting signs. Hypotension was found more frequently among COVID-19 (+) patients (46.7% vs. 12.0%, p = 0,003, 95% CI). Most patients had abnormal WBC, coagulopathy, elevated inflammatory markers, and cardiac biomarkers. Sinus tachycardia, regular sinus rhythm, ST-T wave changes, and low voltage QRS were common ECG findings. The most common chest X-ray results were pleural effusion (80%), pneumonia (71.1%), and enlarged cardiac border (42.2%). Majority of echocardiographic findings were large effusion (>2 cm) (97.8%), RV collapse (40%), and RA collapse (23.3%). An average of 628 ml of pericardial effusion was drained, predominantly serous and exudative. One specimen yielded a positive AFB culture. 6.7% showed carcinoma cells on fluid cytology. The pericardium was normal in 78.9%. 10.0% of the pericardial biopsy specimen had carcinoma, with metastatic cancer being the most common etiology. The most common cancers were lymphoma (22.7%), breast (25.8%), and lung (16.7%). Hospital length of stay was 18 days in COVID-19 (+) patients and 12 days in COVID (-). The complication and in-hospital mortality rate in the COVID-19 (+) compared to the (-) group (86.7% vs. 73.3% and 46.7% vs. 41.3%, respectively) were not statistically significant. The most common complications were respiratory failure (60%), shock (53.3%), and nosocomial pneumonia (40%). There was no association between clinical factors and the risk for complications. Any complication increased the risk for mortality (OR 15.0, 95% CI 3.2-19.7, p=0.002). The presence of hypertension (OR 0.08, 95% CI 0.02 to 0.4, p=0.001) and subacute duration (OR 0.3, 95% CI 0.09 -0.9, p=0.045) decreased the mortality risk.

Profiles were similar in both groups. There was no association between patient profile and complications. Having COVID-19 did not affect patient outcome. The presence of any complication increases the risk of mortality. In-hospital mortality was high at 42.2%.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.