Automated prothrombin-time test with use of a chromogenic peptide substrate and a centrifugal analyzer

We modified a test for prothrombin time, to automate its performance by centrifugal analysis. The sample is activated with calcium-thromboplastin in the presence of a thrombin-specific chromogenic peptide substrate, Tos-Gly-Pro-Arg-p-nitroaniline (Chromozym TH). The endpoint of the reaction is set as the time after onset until a defined amount of substrate has been cleaved, as reflected in a fixed change in absorbance. The assay is as sensitive as clotting-type methods are to the clotting factors of the extrinsic pathway--except for fibrinogen, which can be estimated from the maximum absorbance difference. Substrate concentration has little effect on the result, and varying it does not significantly change the sensitivity to factor X, which indicates little interference with the enzymes of the coagulation cascade. The method was applied to the Cobas Bio centrifugal analyzer. An external calculator must be used to convert absorbance readings into reaction times, which can be expressed as percent-of-normal values or as "ratios" by use of reagent-specific factors. CVs were less than 2% within run, less than 6% day to day. Overall correlation with the clotting test (r = 0.95) was good. Using the Cobas Bio, we achieved a throughput rate of 200 samples per hour.     

Trends in management and outcomes of pulmonary embolism with a multidisciplinary response team

Journal of Thrombosis and Thrombolysis - Multidisciplinary pulmonary embolism (PE) response teams have garnered widespread adoption given the complexities of managing acute PE and provide a...     

Metastases of Cutaneous Squamous Cell Carcinoma Seem to be the Most Frequent Malignancies in the Parotid Gland: A Hospital-Based Study From a Salivary Gland Center

Malignant parotid tumors account for approximately 20% of all parotid lesions. In addition to the various primary parotid lesions there are secondary parotid malignancies, such as metastases or lymphomas. Data on histopathological distribution of all malignancies—including secondary parotid lesions—is limited. Recent evidence indicated a rising surgical incidence of secondary parotid malignancies. This study aims to review the distribution of malignancies in parotid resections from a salivary gland center. A retrospective review of prospectively collected data for all patients who had received parotidectomy between 2014 and 2019 was performed. Histopathological distribution was displayed separately for all parotid malignancies and for primary parotid malignancies. Further, patients` characteristics were compared between benign and malignant parotid lesions and between the two most common malignant parotid lesions. Out of 777 patients, 614 (78.9%) patients had a benign and 164 (21.1%) patients had a malignant parotid lesion. The most common parotid malignancy was metastatic cutaneous squamous cell carcinoma (cSCC) accounting for 35.4% of all parotid malignancies. 71.5% of all malignant lesions were secondary malignancies. Patients with metastatic cSCC were significantly older (p < 0.001) and significantly more likely to be male (p < 0.001) than patients with primary parotid malignancies. No significant difference was found when the lesion size of metastatic cSCC was compared to primary parotid malignancies (p = 0.216). The present study shows the high prevalence of secondary parotid malignancies in patients who had received parotidectomy. Furthermore, it confirms a rising surgical incidence of metastatic cSCC to the parotid gland in a series from a salivary gland center. At this time, parotid surgery for malignant lesions is more likely to be performed for metastases than for primary parotid malignancies.     

Can Ultrasound in Combination with Virtual Touch Imaging Quantification Predict the Dignity of a Parotid Tumor?

Pre-operative evaluation of a parotid gland tumor is crucial in guiding treatment. This study evaluates the diagnostic performance of B-mode ultrasound in combination with Virtual Touch imaging quantification (VTIQ) in the assessment of parotid lesions. A prospective study of 268 patients with parotid lesions was conducted. Pre-operative ultrasound findings and VTIQ data were compared against histologic results. Ill-defined margins on ultrasound were associated with a significantly higher risk of malignancy (odds ratio [OR] = 1224.0, 95 % confidence interval [CI]: 151.8–9872.7). Faster mean shear waves on VTIQ (OR = 1.81, 95% CI: 1.47–2.23, per 1 m/s increase) and an area with shear wave velocity >6.0 m/s involving >70 % of the lesion (OR = 19.80, 95 % CI: 6.22–63.07) were associated with higher risk of malignancy. Addition of VTIQ to routine pre-operative B-mode ultrasound can provide supplemental information on the dignity of a parotid tumor, allowing for peri-operative procedural optimization.     

The importance of proteolysis as the initial step of insulin degradation in rat liver homogenates.

It was previously proposed (Varandani, P. T., Proc Natl Acad Sci 69:1681, 1972) that insulin is first degraded by rat liver homogenates in an enzyme-catalyzed reductive process by microsomal glutathione-insulin transhydrogenase before being proteolytically cleaved by the cytosolic enzyme activity designated insulin protease. This study was, however, carried out with concentrations of the hormone 10,000 times the maximal concentration seen in peripheral blood. In the present study, physiological levels of insulin (approximately 0.1 nM) and concentrations of reduced and oxidized glutathione approximating the reductive potentials of normal liver were used. Rates of degradation by separable particulate and soluble components of the homogenate were determined by following enzymatic conversion of [125I]-iodoinsulin to the trichloroacetic acid-solube form. Assessment of the mode of degradation was determined by gel filtration on Sephadex G-50 in the presence of 1 M acetic acid-6M urea. From these studies it was seen that 1) insulin is reduced at a very significant rate nonenzymatically; 2) during short periods of incubation (30 sec) where no significant hormone is reduced nonenzymatically, the rate of cleavage by the insulin protease present in the cytosol is extremely high and the microsomal GIT activity is negligible; and 3) insulin destruction noted in isolated liver cells and perfused liver is most probably due to the insulin protease activity of the cytosol.     

Impact of comorbidities on health status measured using the Kansas City Cardiomyopathy Questionnaire in patients with heart failure with reduced and preserved ejection fraction

Aim

Patients with heart failure (HF) often suffer from a range of comorbidities, which may affect their health status. The aim of this study was to assess the impact of different comorbidities on health status in patients with HF and reduced (HFrEF) and preserved ejection fraction (HFpEF).

Methods and results

Using individual patient data from HFrEF (ATMOSPHERE, PARADIGM-HF, DAPA-HF) and HFpEF (TOPCAT, PARAGON-HF) trials, we examined the Kansas City Cardiomyopathy Questionnaire (KCCQ) domain scores and overall summary score (KCCQ-OSS) across a range of cardiorespiratory (angina, atrial fibrillation [AF], stroke, chronic obstructive pulmonary disease [COPD]) and other comorbidities (obesity, diabetes, chronic kidney disease [CKD], anaemia). Of patients with HFrEF (n = 20 159), 36.2% had AF, 33.9% CKD, 33.9% diabetes, 31.4% obesity, 25.5% angina, 12.2% COPD, 8.4% stroke, and 4.4% anaemia; the corresponding proportions in HFpEF (n = 6563) were: 54.0% AF, 48.7% CKD, 43.4% diabetes, 53.3% obesity, 28.6% angina, 14.7% COPD, 10.2% stroke, and 6.5% anaemia. HFpEF patients had lower KCCQ domain scores and KCCQ-OSS (67.8 vs. 71.3) than HFrEF patients. Physical limitations, social limitations and quality of life domains were reduced more than symptom frequency and symptom burden domains. In both HFrEF and HFpEF, COPD, angina, anaemia, and obesity were associated with the lowest scores. An increasing number of comorbidities was associated with decreasing scores (e.g. KCCQ-OSS 0 vs. ≥4 comorbidities: HFrEF 76.8 vs. 66.4; HFpEF 73.7 vs. 65.2).

Conclusions

Cardiac and non-cardiac comorbidities are common in both HFrEF and HFpEF patients and most are associated with reductions in health status although the impact varied among comorbidities, by the number of comorbidities, and by HF phenotype. Treating/correcting comorbidity is a therapeutic approach that may improve the health status of patients with HF.     

Knowledge about self-efficacy and outcomes in patients with heart failure and reduced ejection fraction

Aim

Although education in self-management is thought to be an important aspect of the care of patients with heart failure, little is known about whether self-rated knowledge of self-management is associated with outcomes. The aim of this study was to assess the relationship between patient-reported knowledge of self-management and clinical outcomes in patients with heart failure and reduced ejection fraction (HFrEF).

Methods and results

Using individual patient data from three recent clinical trials enrolling participants with HFrEF, we examined patient characteristics and clinical outcomes according to responses to the ‘self-efficacy’ questions of the Kansas City Cardiomyopathy Questionnaire. One question quantifies patients' understanding of how to prevent heart failure exacerbations (‘prevention’ question) and the other how to manage complications when they arise (‘response’ question). Self-reported answers from patients were pragmatically divided into: poor (do not understand at all, do not understand very well, somewhat understand), fair (mostly understand), and good (completely understand). Cox-proportional hazard models were used to evaluate time-to-first occurrence of each endpoint, and negative binomial regression analysis was performed to compare the composite of total (first and repeat) heart failure hospitalizations and cardiovascular death across the above-defined groups. Of patients (n = 17 629) completing the ‘prevention’ question, 4197 (23.8%), 6897 (39.1%), and 6535 (37.1%) patients had poor, fair, and good self-rated knowledge, respectively. Of those completing the ‘response’ question (n = 17 637), 4033 (22.9%), 5463 (31.0%), and 8141 (46.2%) patients had poor, fair, and good self-rated knowledge, respectively. For both questions, patients with ‘poor’ knowledge were older, more often female, and had a worse heart failure profile but similar treatment. The rates (95% confidence interval) per 100 person-years for the primary composite outcome for ‘poor’, ‘moderate’ and ‘good’ self-rated knowledge in answer to the ‘prevention’ question were 12.83 (12.11–13.60), 12.08 (11.53–12.65) and 11.55 (11.00–12.12), respectively, and for the ‘response’ question were 12.88 (12.13–13.67), 12.22 (11.60–12.86) and 11.56 (11.07–12.07), respectively. The lower event rates in patients with ‘good’ self-rate knowledge were accounted for by lower rates of cardiovascular (and all-cause) death and not hospitalization for worsening heart failure.

Conclusions

Poor patient-reported ‘self-efficacy’ may be associated with higher rates of mortality. Evaluation of knowledge of ‘self-efficacy’ may provide prognostic information and a guide to which patients may benefit from further education about self-management.