Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma

Background: To clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci. Methods: The present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated. Results: A total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm3 tumors increased according to the upgrade of Likert scores (score 1 or 2: 33 %; score 3: 68.8 %; score 4 or 5: 90.9 %, χ2 test, p 7 also increased from scale 2 to scale 5 (scale 2: 0 %; scale 3: 56.3 %; scale 4: 72.7 %; 5: 90.9 %, χ2 test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm3 (<0.2 cm3: 10.3 %; 0.2-0.5 cm3: 25 %; 0.5-1.0 cm3: 66.7 %; 1.0 < cm3: 92.1 %). Conclusions: Each Likert scale favobably reflected the corresponding tumor’s volume and Gleason score. Our observations show that “score 3 or higher” could be a useful threshold to predict clinically significant carcinoma when considering treatment options

Total aortic arch replacement under intermittent pressure-augmented retrograde cerebral perfusion

Kitahori, Kawata, Takamoto et al. described the effectiveness of a novel protocol for retrograde cerebral perfusion that included intermittent pressure augmentation for brain protection in a canine model. Based on their report, we applied this novel technique clinically. Although the duration of circulatory arrest with retrograde cerebral perfusion was long, the patient recovered consciousness soon after the operation and had no neurological deficit. Near-infrared oximetry showed recovery of intracranial blood oxygen saturation every time the pressure was augmented

Detection of tissue T-cell in patients with chronic active hepatitis using fragmented sheep red blood cell (SRBC) membrane.

Fragmented sheep red blood cell (SRBC) membrane was used for detection of T-cells in liver biopsy specimens from patients with chronic active hepatitis. SRBC was separated with Lymphoprep, sonicated, then filtered through a 3 mu Millipore-membrane as a fragmented SRBC reagent. Tissue T-cells were stained by an indirect immunofluorescent technique using SRBC reagent and fluorescein isothiocyanate (FITC)-labelled rabbit anti-SRBC. Positively staining lymphocytes were present in portal tracts and in areas of piecemeal necrosis. There also seemed to be a positive correlation between the number of positively staining lymphocytes and the activity of chronic hepatitis; numerous lymphocytes being stained in areas of severe piecemeal necrosis. Our findings suggest that the fragmented SRBC technique for detection of T-cells is reliable and reproducible, that it could be used as a clinical routine method, and that it is useful for further elucidating the nature of host immune reactions on tissue levels.

Tissue immune complexes demonstrated in the liver of patients with chronic aggressive hepatitis using FITC-labelled human Clq.

Immune complexes in liver specimens from 10 patients with chronic liver diseases [2 with chronic persistent hepatitis (CPH), 3 with chronic aggressive hepatitis (CAH) of moderate activity, 3 with CAH of severe activity, and 2 with liver cirrhosis] were examined by a technique of direct immunofluorescence using FITC-labelled human purified Clq (FITC-Clq). FITC-Clq bound to the nuclei of all cells in liver tissue. After DNase treatment, positive nuclei were absent, but positive staining with FITC-Clq remained in amorphous deposits and hepatic cell membranes in the areas of piecemeal necrosis of four CAH patients. Since FITC-Clq could not be demonstrated in the liver tissue of CPH and liver cirrhosis which contained no piecemeal necrosis, positive fluorescence in the liver of CAH patients was thought to indicate immune complexes bound to FITC-Clq. The fact that these positive substances, however, were few in number, may be the result of physiological mechanisms of immune clearance which rapidly eliminate immune complexes from the body.</p

Existence of serum HBe antigen and expression of liver HB surface and core antigens in hepatitis type B patients.

A study of 52 liver biopsies (47 hepatitis type B and 5 asymptomatic carriers) was performed to clarify the roles of HBe antigen (HBeAg), HB surface antigen (HBsAg) and HB core antigen (HBcAg). In this study, the Gudat classification was modified so as to classify the patterns of HB antigens into six reaction types including: type O (negative for both liver HBsAg and liver HBcAg), type III-A (characterized by a spotty HBsAg pattern) and type III-B (characterized from a sub-lobular to lobular HBsAg localization pattern). This classification enabled accurate prediction of the prognosis of hepatitis. Patients with positive serum HBeAg had either minimal hepatitis with mild clinical features or chronic aggressive hepatitis with severe clinical features. Ten patients negative for both HBeAg and HBeAb were all positive for liver HBcAg. In all 3 patients on corticosteroid administrations liver tissue was markedly positive for HBcAg and serum was usually positive for HBeAb.</p

Development of a Multi-Step Leukemogenesis Model of MLL-Rearranged Leukemia Using Humanized Mice

Mixed-lineage-leukemia (MLL) fusion oncogenes are intimately involved in acute leukemia and secondary therapy-related acute leukemia. To understand MLL-rearranged leukemia, several murine models for this disease have been established. However, the mouse leukemia derived from mouse hematopoietic stem cells (HSCs) may not be fully comparable with human leukemia. Here we developed a humanized mouse model for human leukemia by transplanting human cord blood-derived HSCs transduced with an MLL-AF10 oncogene into a supra-immunodeficient mouse strain, NOD/Shi-scid, IL-2Rγ−/− (NOG) mice. Injection of the MLL-AF10-transduced HSCs into the liver of NOG mice enhanced multilineage hematopoiesis, but did not induce leukemia. Because active mutations in ras genes are often found in MLL-related leukemia, we next transduced the gene for a constitutively active form of K-ras along with the MLL-AF10 oncogene. Eight weeks after transplantation, all the recipient mice had developed acute monoblastic leukemia (the M5 phenotype in French-American-British classification). We thus successfully established a human MLL-rearranged leukemia that was derived in vivo from human HSCs. In addition, since the enforced expression of the mutant K-ras alone was insufficient to induce leukemia, the present model may also be a useful experimental platform for the multi-step leukemogenesis model of human leukemia

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362