Hypertension is a common toxicity induced by bevacizumab and other antiangiogenic drugs. There are no biomarkers to predict the risk of bevacizumab-induced hypertension. This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for hypertension were estimated. Five proteins showed no difference in levels between clinical trials and were used for analyses. Lower levels of angiopoietin-2 (p?=?0.0013, OR 3.41, 95% CI 1.67–7.55), VEGF-A (p?=?0.0008, OR 4.25, 95% CI 1.93–10.72), and VCAM-1 (p?=?0.0067, OR 2.68, 95% CI 1.34–5.63) were associated with an increased risk of grade 3 hypertension. The multivariable model suggests independent effects of angiopoietin-2 (p?=?0.0111, OR 2.71, 95% CI 1.29–6.10), VEGF-A (p?=?0.0051, OR 3.66, 95% CI 1.54–9.73), and VCAM-1 (p?=?0.0308, OR 2.27, 95% CI 1.10–4.92). The presence of low levels of 2–3 proteins had an OR of 10.06 (95% CI 3.92–34.18, p?=?1.80?×?10–5) for the risk of hypertension, with sensitivity of 89.7%, specificity of 53.5%, PPV of 17.3%, and NPV of 97.9%. This is the first study providing evidence of plasma proteins with potential value to predict patients at risk of developing bevacizumab-induced hypertension.
Aim: To study hepatitis C virus (HCV) selection and hypervariable region-1 (HVR1) evolution in a chimpanzee chronically infected with HCV-1 over 12 years after inoculation with a human factor VIII concentrate contaminated with HCV. Methods: From the inoculum, the earliest chimpanzee plasma and 12 annual plasma samples, HCV fragments including HVR1 were amplified followed by cloning and sequencing. Results: Five HCV subtypes - 1a, 1b, 2a, 2b, 3a - and multiple 1a strains were identified in the inoculum. Two 1a strains were found in the earliest chimpanzee sample, while a single HCV-1 strain was detected in the 12 annual samples. None of the chimpanzee sequences were identical to those found in the inoculum. Over 12 years, HVR1 patterns changed irregularly, but a few patterns showed identical nucleotide or amino acid sequences. In the last three years, the variety of HVR1 patterns decreased, while the proportion of major patterns increased. These corresponded to a higher virus load and a lower number of amino acid substitutions. Simultaneously, the HVR1 sequences became more similar to the consensus sequence of the 1a subtype. Conclusion: HCV selection was observed from the inoculum to the inoculated chimpanzee and from the early acute hepatitis to the persistent chronic infection. The selection occurred at three levels: among subtypes after transmission, among isolates during acute hepatitis and among quasispecies in chronic infection. 相似文献
Emergency Radiology - The COVID-19 pandemic has affected healthcare systems and patients alike across the USA. We seek to elucidate changes in abdominal imaging ordered from the emergency... 相似文献
Begomoviruses are emerging as serious threat to many crops throughout the world particularly in tropical and sub-tropical regions. A leaf curl disease with symptoms typical of infection by many begomoviruses was observed in French bean (Phaseolus vulgaris) at Kanpur, India, during 2010–2012. The disease caused downward leaf curling and made the plants unproductive. The disease was transmitted from infected to healthy plants through whitefly (Bemisia tabaci). The products of five samples digested with EcoRI yielded DNA fragments of about 2.7 kb. The complete sequence of the Fb1 sample comprised 2,741 nucleotides with genome organization typical of begomoviruses having two ORFs in virion-sense and five ORFs in complementary-sense separated by an intergenic region with begomovirus conserved nonanucleotide sequence, TAATATTAC. The complete DNA-A sequence homology was most closely related to Cotton leaf curl Bangalore virus with 80 % nucleotide sequence identity. Based on the demarcation criteria for identifying a begomovirus species, Fb1 is considered as a distinct begomovirus species, named French bean leaf curl virus and designated as FbLCV-[IN:Knp:12]. The complete sequence of associated satellite DNA-β comprises 1,379 nucleotides with single ORF and has 80 % identity with Papaya leaf curl beta satellite. There was no evidence of recombination in DNA-A of FbLCV and associated beta satellite DNA molecule. 相似文献
Clinical and Experimental Medicine - The development of new therapies based on tumor biology is one of the main topics in cancer treatment. In this regard, investigating the... 相似文献
N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19. 相似文献
A number of different methods exist to assess clinical stability, a key component of pneumonia management. We compared the prognostic value of different stability criteria through a secondary analysis of the Edinburgh pneumonia study database. We studied four clinical stability criteria (Halm's criteria, the ATS criteria, CURB and 50% or more decrease in C-reactive protein from baseline). Outcomes included 30-day mortality, need for mechanical ventilation or vasopressor support (MV/VS), development of a complicated pneumonia, and a combined outcome of the above. A total of 1079 patients (49.8% male), with a median age of 68 years (IQR 53–80), were included. Ninety-three patients (8.6%) died by day 30, 91 patients (8.4%) required MV/VS and 99 patients (9.2%) developed a complicated pneumonia. Patients with increasing severity of pneumonia on admission, assessed by both CURB-65 and PSI, took a progressively longer time to achieve clinical stability assessed by any method (p < 0.001 for all criteria). Halm's criteria had the highest area under the curve (AUC) for prediction of 30-day mortality (AUC 0.95 (0.94–0.96)), need for MV/VS (AUC 0.96 (0.95–0.97)) and combined adverse outcome (AUC 0.96 (0.95–0.97)). C-reactive protein had the highest area under the curve for complicated pneumonia (AUC 0.96 (0.95–0.97)). Adding C-reactive protein to Halm's criteria increased the area under the curve, but the difference was only statistically significant for complicated pneumonia. All of the criteria performed well in predicting adverse outcomes in patients with pneumonia. Halm's criteria performed best when identifying patients at low risk of complications. 相似文献
OBJECTIVE: To assess health care practitioners' ability to correctly measure the QT interval, and to identify factors and medications that may increase the risk of QT-interval prolongation and torsades de pointes. DESIGN: A cross-sectional analysis of a survey administered between April 2002 and March 2003. PARTICIPANTS AND SETTING: Health care practitioners attending Grand Rounds Conferences at 6 academic institutions in the United States in internal medicine and psychiatry and at 6 community hospitals in the same geographical areas as the academic institutions. INTERVENTION: Anonymous, self-administered questionnaire that included 20 questions on the QT interval. MEASUREMENTS AND MAIN RESULTS: Of approximately 826 attendees, 517 (63%) completed the survey. Of about 608 attendees of internal medicine conferences, 371 (61%) responded, and of about 208 attendees of psychiatry conferences, 146 (67%) responded. Of a total number of 20 questions, the median number of correct answers for the whole group was 10 (interquartile range 7-13). The median number of correct answers for internists was 12 (interquartile range 9-13), for psychiatrists 10 (interquartile range 7-13), and for other specialists 10 (interquartile range 5-13). Respondents who graduated between 1990 and 1999 and academicians performed significantly better overall than other respondents. Of the 517 respondents, 224 (43%) measured the QT interval correctly. Physicians in training and academicians were more likely to measure the QT interval correctly. CONCLUSION: The majority of health care practitioners cannot correctly measure the QT interval and cannot correctly identify factors and medications that can prolong the QT interval. Our findings suggest that greater attention to the QT interval is warranted to ensure safer use of QT prolonging medications. 相似文献