real life triplet fir fox chemotherapy in first line metastatic pancreatic ductal adenocarcinoma recommended schedule for expected activity and safety and phase ii study

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Biparametric (bp) and multiparametric (mp) magnetic resonance imaging (MRI) approach to prostate cancer disease: a narrative review of current debate on dynamic contrast enhancement

Prostate cancer is the most common malignancy in male population. Over the last few years, magnetic resonance imaging (MRI) has proved to be a robust clinical tool for identification and staging of clinically significant prostate cancer. Though suggestions by the European Society of Urogenital Radiology to use complete multiparametric (mp) T2-weighted/diffusion weighted imaging (DWI)/dynamic contrast enhancement (DCE) acquisition for all prostate MRI examinations, the real advantage of functional DCE remains a matter of debate. Recent studies demonstrate that biparametric (bp) and mp approaches have similar accuracy, but controversial evidences remain, and the specific potential benefits of contrast medium administration are still poorly discussed in literature. The bp approach is in fact sufficient in most cases to adequately identify a negative test, or to accurately define the degree of aggressiveness of a lesion, especially if larger or with major characteristics of malignancy. This feature would give the DCE a secondary role, probably limited to a second evaluation of the lesion location, for detecting small cancer or in case of controversy. However, DCE has proved to increase the sensitivity of prostate MRI, though a less specificity. Therefore, an appropriate decision algorithm is needed to standardize the MRI approach. Aim of this review study was to provide a schematic description of bpMRI and mpMRI approaches in the study of prostatic anatomy, focusing on comparative validity and current DCE application. Additional theoretical considerations on prostate MRI are provided

Evaluation of Brix Refractometry to Estimate Immunoglobulin G Content in Buffalo Colostrum and Neonatal Calf Serum

Brix refractometry has been widely demonstrated to be a useful tool for monitoring colostrum management program and passive immunity transfer (PIT) in Bovines, but its suitability has never been verified in Buffalo. Therefore, the objective of this study was to evaluate the utility of a simple and rapid tool such as a digital Brix refractometer to estimate colostrum quality and for evaluating the success of passive transfer of immunoglobulin G (IgG) in Buffalo calves. The optimal cut points levels for Brix Refractometry for distinguishing good- and poor-quality colostrum and for assessing the adequacy of passive immunity transfer in calves were determined. For this aim, 26 first-milking maternal colostrum (MC) were collected from first-calf heifers. Blood samples were obtained from their calves at birth (T0) and 72 hours after (T3). Colostrum and Serum IgG content were determined by indirect enzyme-linked immunosorbent assay (ELISA), whereas total protein (TP, g/dL) and percentage Brix (%Brix) by means of a digital Brix refractometer. The mean colostrum IgG was 64.9 ± 29.3 mg/mL. The mean serum %Brix at T3 was 9.6 ± 0.9%. The mean serum IgG content at T3 was 11.1 ± 2.0 mg/mL. Pearson’s correlation coefficient (rp) was determined between Brix and ELISA measurements: colostrum %Brix showed a significant correlation with serum %Brix (rp = 0.82, p < 0.001); serum %Brix was highly correlated with serum TP (STP, g/dL) (rp = 0.98, p < 0.001) and serum IgG (mg/mL) (rp = 0.85, p < 0.001). A cut point of 18% Brix to estimate samples of MC ≥ 50 mg/mL from first-calf heifers was more appropriate for the buffalo. A cut point of 8.4% Brix resulted in the greatest percentage of calf serum samples being correctly classified. Based on our findings, a digital Brix refractometer could be a useful tool to monitor colostrum quality and to estimate PIT in Buffalo calves

A model for determining cardiac mitochondrial substrate utilisation using stable 13 C-labelled metabolites

Abstract: Introduction: Relative oxidation of different metabolic substrates in the heart varies both physiologically and pathologically, in order to meet metabolic demands under different circumstances. 13C labelled substrates have become a key tool for studying substrate use—yet an accurate model is required to analyse the complex data produced as these substrates become incorporated into the Krebs cycle. Objectives: We aimed to generate a network model for the quantitative analysis of Krebs cycle intermediate isotopologue distributions measured by mass spectrometry, to determine the 13C labelled proportion of acetyl-CoA entering the Krebs cycle. Methods: A model was generated, and validated ex vivo using isotopic distributions measured from isolated hearts perfused with buffer containing 11 mM glucose in total, with varying fractions of universally labelled with 13C. The model was then employed to determine the relative oxidation of glucose and triacylglycerol by hearts perfused with 11 mM glucose and 0.4 mM equivalent Intralipid (a triacylglycerol mixture). Results: The contribution of glucose to Krebs cycle oxidation was measured to be 79.1 ± 0.9%, independent of the fraction of buffer glucose which was U-13C labelled, or of which Krebs cycle intermediate was assessed. In the presence of Intralipid, glucose and triglyceride were determined to contribute 58 ± 3.6% and 35.6 ± 0.8% of acetyl-CoA entering the Krebs cycle, respectively. Conclusion: These results demonstrate the accuracy of a functional model of Krebs cycle metabolism, which can allow quantitative determination of the effects of therapeutics and pathology on cardiac substrate metabolism

Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis

Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data represent procedures performed at 3 tertiary care facilities within a large health system operating in the New York City metropolitan area. The overall 30-day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable findings for hemodynamically unstable patients were 12.5% and 13.4 days, respectively. Acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise; however, caution is warranted. Our outcomes might be dependent upon institutional capability, experience, surgical ability, and careful patient selection

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London