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Purpose [68 Ga]Ga-PSMA-11 is a promising radiopharmaceutical for detecting tumour lesions in prostate cancer, but knowledge of the pharmacokinetics is limited. Dynamic PET-CT was performed to investigate the tumour detection and differences in temporal distribution, as well as in kinetic modelling of [68 Ga]Ga-PSMA-11 by tissue type. Methods Dynamic PET-CT over the lower abdomen and static whole-body PET-CT 80–90 min p.i. from 142 patients with biochemical recurrence were retrospectively analysed. Detection rates were compared to PSA levels. Average time-activity curves were calculated from tumour lesions and normal tissue. A three-compartment model and non-compartment model were used to calculate tumour kinetics. Results Overall detection rate was 70.42%, and in patients with PSA > 0.4 ng/mL 76.67%. All tumour lesions presented the steepest standardised uptake value (SUV) incline in the first 7–8 min before decreasing to different degrees. Normal tissue presented with a low uptake, except for the bladder, which accumulated activity the steepest 15–16 min. p.i.. While all tumour lesions continuously increased, bone metastases showed the steepest decline, resulting in a significantly lower SUV than lymph node metastases (60 and 80–90 min). Transport rate from the blood and tracer binding and internalisation rate were lower in bone metastases. Heterogeneity (fractal dimension) and vascular density were significantly lower in bone metastases. Conclusion Even at low PSA between 0.51 and 0.99 ng/mL, detection rate was 57%. Dynamic imaging showed a time window in the first 10 min where tumour uptake is high, but no bladder activity is measured, aiding accuracy in distinction of local recurrence. Kinetic modelling provided additional information for tumour characterisation by tissue type.

In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as the causative agent for coronavirus disease 2019 (COVID-19), a clinical syndrome with high incidence of acute respiratory distress syndrome (ARDS). Part of the pathophysiology of COVID-19-induced ARDS is explained by increased dead space ventilation from pulmonary microthrombi; this is supported by the existence of alveolar capillary microthrombi found on autopsies [1, 2]. This has prompted the use of therapeutic anticoagulation and thrombolytics [3–5]. Thus far, no clinical trials have been completed to evaluate the use of recombinant tissue-type plasminogen activator (rt-PA) to treat COVID-19. The objective of this study was to determine whether rt-PA administration decreases dead space ventilation in patients with COVID-19., COVID19-induced ARDS is partly explained by the presence of microthrombi, motivating the use of thrombolytics. This study shows that thrombolytics decrease dead space ventilation in COVID-19 ARDS patients. https://bit.ly/2GdM44a

This research aimed to expand the nanomaterial-based drug loading method for the recombinant tissue plasminogen activator (rtPA) treatment of acute phase thrombolysis in ischemic stroke. In this research, the coprecipitation method was used to prepare Fe3O4 magnetic nanomaterials. Polyacrylic acid (PAA) was coated on the surface of the nanomaterials. The nanomaterials were subjected to hydroxyl activation treatment so that it could be connected to rtPA. By EDC/NHSS method, rtPA was covalently attached to the surface of nanomaterials to form a composite nanomaterial that was modified by rtPA, which was FPA-rtPA. Firstly, the material was characterized, then the pharmacokinetics of the material was evaluated. Finally, the thrombus targeting and thrombolytic properties of the material were analyzed. In the experiment, Fe3O4, FPA, PAA, and FPA-PAA were monitored by FT-IR, the peak value of PAA at 1834 cm–1 meant C=O group, and PAA-FPA had a similar peak, each milligram of nanomaterial can be combined with 80.6 μg ± 1.4 μg of rtPA. In the pharmacokinetic test, the half-life of FPA-rtPA was 90 min, which was much higher than the half-life of rtPA in the free state (P < 0.001), so it was suitable as a targeted thrombolytic preparation; the fluorescence intensity of the FPA-rtPA group combined with the fibrin blood clot was significantly stronger than the FPA group, and rtPA-FPA can target fibrin thrombosis in the cerebral thrombosis model. After comparing the postoperative cerebral infarction area, the rtPA-FPA-based group of rats had a significant decrease in cerebral infarction area (P < 0.001), thus the nanomaterials had better thrombolytic properties.

Background and Purpose: In large artery occlusion stroke, both intravenous (IV) tPA (tissue-type plasminogen activator) and endovascular stroke treatment (EST) are standard-of-care. It is unknown how often tPA causes distal embolization, in which a procedurally accessible large artery occlusion is converted to a more distal and potentially inaccessible occlusion. Methods: We analyzed data from a decentralized stroke telemedicine program in an integrated healthcare delivery system covering 21 hospitals, with 2 high-volume EST centers. We captured all cases sent for EST and examined the relationship between IV tPA administration and the rate of distal embolization, the rate of target recanalization (modified Treatment in Cerebral Infarction scale 2b/3), clinical improvement before EST, and short-term and long-term clinical outcomes. Results: Distal embolization before EST was quite common (63/314 [20.1%]) and occurred more often after IV tPA before EST (57/229 [24.9%]) than among those not receiving IV tPA (6/85 [7.1%]; P P Conclusions: IV tPA administration before EST for large artery occlusion is associated with distal embolization, which in turn may reduce the chance that EST can be attempted and recanalization achieved. At the same time, some IV tPA-treated patients show symptomatic improvement and complete recanalization. Because IV tPA is associated with both distal embolization and improved long-term clinical outcome, there is a need for prospective clinical trials testing the net benefit or harm of IV tPA before EST.

To investigate the expression level and clinical significance of fucosidase (AFU), glutamyltranspeptidase (GGT), and thymidine kinase 1 (TK1) in the serum of patients with primary liver cancer (PHC). A total of 135 PHC patients in Baoji Central Hospital from September 2014 to February 2018 were selected as a research group (RG), while 127 healthy subjects were collected as a control group (CG). Enzyme-linked immunosorbent assay (ELISA) was used to detect the AFU, GGT, and TK1 concentrations in serum of the two groups, and the diagnostic value of combined detection of the three for PHC was analyzed. AFU, GGT, and TK1 concentrations in serum of the RG were dramatically higher than those of the CG (P< 0.050). ROC curve analysis showed that the sensitivity of AFU, GGT, and TK1 in the single diagnosis of PHC was 88.00, 94.00, and 66.00% respectively, and the specificity was 68.00, 54.00, and 66.00% respectively. The sensitivity and specificity of the combined diagnosis of PHC were 76.00 and 90.00%, respectively. AFU, GGT, and TK1 concentrations were different in the presence or absence of liver cirrhosis, TNM stage, and tissue type (P< 0.050). AFU, GGT, and TK1 concentrations in PHC patients were dramatically higher than those in healthy people. Combined detection of the three has good diagnostic value for PHC.

Aortic thrombosis during neonatal period is a rare event especially when it is not related to umbilical arterial catheters. A case of a premature infant with a gestational age of 25 weeks who suddenly developed, at the age of 44 days, poor arterial saturation (SaO2 60%) and legs pale and painful, is reported. In this patient, arterial and venous eco-color Doppler showed a complete aortic thrombosis distal to the renal arteries of unknown etiology. Thrombolytic therapy with tissue-type plasminogen activator (t-PA) was immediately started with a bolus dose of 0.5 mg/kg/h followed by a continuous infusion of 0.2 mg/kg/h. Fresh frozen plasma was also infused in order to increase the concentration of plasminogen. We tried with success to avoid bleeding complications maintaining fibrinogen concentration over 500 mg/L and platelets over 100,000x109/L. Heparinisation with enoxaparin was started after 5 days of t-PA treatment and continued for 85 days. The premature infant recovered but physiotherapy and splints were needed for talipes equinovarus resulted as a consequence of distal thrombosis. Conclusion: The strategy for treating an acute arterial thrombosis in a neonate may include thrombolytic therapy with t-PA, taking into account that the rate of plasmin generation in newborns and overall activity is decreased compared to adults. The impaired response of newborns may be enhanced not by increasing the dose of t-PA but increasing plasminogen through fresh frozen plasma infusion.

Controversy persists regarding the safety and efficacy of an accelerated low-dose recombinant tissue-type plasminogen activator (rt-PA) regimen for reperfusion therapy in acute pulmonary embolism. This study describes the outcomes of an accelerated low-dose rt-PA regimen for the treatment of acute pulmonary embolism in Vietnamese patients. This was a case series from October 2014 to October 2020 from 9 hospitals across Vietnam. Patients presenting with acute pulmonary embolism with high to intermediate mortality risk were administered alteplase 0.6 mg per kilogram (maximum of 50 mg) over 15 min. The main outcomes were the proportion who survived to hospital discharge and at 3 months as well as in-hospital hemorrhage (major and minor according to International Society of Thrombosis and Hemhorrage definitions). A total of 80 patients were enrolled: 48 (60%) with high risk for mortality and 32 patients (40%) with intermediate risk for mortality. A total of 7 (8.8%) died in hospital. All deaths occurred in the high-risk mortality group. The 73 patients who were discharged alive remained alive at 3 months follow up. During hospitalization, 1 patient (1.3%) suffered major bleeding, and 7 (8.8%) had minor bleeding. An accelerated thrombolytic regimen with alteplase 0.6 mg/kg (maximum of 50 mg) over 15 min for acute pulmonary embolism appeared be effective and safe in a case series of Vietnamese patients.

Background: It is a debatable topic about the benefit of intravenous (IV) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) for atrial fibrillation (AF) patients with acute ischemic stroke (AIS). This study aimed to identify whether IV rt-PA could improve the short-term outcome of patients with AF-AIS.Methods: Medical data of patients with AIS onset within 72hs admitted in the department of neurologic of our hospital between January 1st, 2015 and December 31, 2020 were extracted. The AF-AIS patients were selected and divided into IV rt-PA group (group A) and non-rt-PA group (group B). The baseline characteristics, imaging changes and modified Rankin Scale (mRS) score (≤ 2 as good prognosis, > 2 as poor, = 6 as death) at discharge were obtained to compare the differences between the two groups. Logistic regression was used to analyze the factors influencing on the outcome. Results: Among a total of 1663 AIS patients, there were 280 had AF, of them 227 AF-AIS cases were conformed to the inclusion criteria, including 45 in group A and 182 in group B. All of AF-AIS patients, 48.0% had larger size of infarction and 62.1% had National Institute of Health stroke scale (NIHSS)score more than 10, the differences in the size and NIHSS between the two groups were not significant. A total of 51 cases (22.5%) died during hospitalization, the difference between group A and group B was not obvious (20.0% vs. 23.1%, P=0.658). The cumulative poor outcome (including deaths) at discharge was 75.3%, the difference between the two groups was also not significant (77.8% vs. 74.7%, P=0.671). The incidence of hemorrhagic transformation (HT) in group A was higher than that of in group B (40.0% vs. 21.4, P=0.010), the same was true for parenchymal hematoma (PH) in group A than group B (22.2% vs. 5.5%, P = 0.001). On univariate analysis, poor outcome was significantly associated with infarct size, NIHSS and PH, but not thrombolysis. The proportion of PH in patients with poor outcome between the two groups was also not remarkable. On adjusted multiple logistic regression analysis, both baseline infarction size [(P=0.013, odds ratio (OR) =4.558, 95% 95% confidence interval (CI): 1.373- 15.133] and NIHSS (PConclusion: Patients with AF-AIS had larger infarction size, higher NIHSS score, higher rate of mortality and worse outcome, for them, the IV rt-PA increased the incidence of PH except significantly improved their short-term prognosis.

Background/aim Pulmonary pleomorphic carcinoma (PPC) is rare, and few studies have reported its features. We assessed the clinicopathological features, surgical outcomes, oncogenic status and programmed death-ligand 1 (PD-L1) expression of PPC. Patients and methods We retrospectively reviewed data from 22 consecutive patients who underwent resection of PPC between 2007 and 2017. Results The predominant tissue type of the epithelial component was adenocarcinoma in 15 patients (68%) and the others in 7 patients (32%), and the 3-year disease-free survival rate tended to be better in patients with an adenocarcinoma component compared to patients with another component (40.0% vs. 17.1%, p=0.059). PD-L1 expression was observed in all eight tumors whose PD-L1 status could be examined and high PD-L1 expression (≥50%) was frequent (5/8, 63%). Conclusion A predominant adenocarcinoma epithelial component in PPC might be associated with better survival outcomes and high PD-L1 expression might be frequent in PPC.

Objective The durability of bioprosthetic heart valve (BHV) devices, commonly made of bovine (BP) and porcine (PP) pericardium tissue, is partly limited by device calcification and tissue degeneration, which has been associated with pathological levels of mechanical stress. This study investigated the impacts of BP and PP tissues with different thicknesses and tissue mechanical properties in BHV applications. Methods Second Harmonic Generation (SHG) imaging was employed to visualize the collagen fibers on each side of the pericardium. Structural constitutive modeling that incorporates collagen fiber distribution obtained from multiphoton microscopy for each tissue type were derived to characterize the corresponding biaxial mechanical testing data collected in a previous study. The models were verified through finite element (FE) simulations of the biaxial test and implemented in valve closing simulations. Results Smooth side collagen fibers were found to correlate with the mechanical response. BHVs with adult (ABP) and calf (CBP) BP tissues had lower maximum principal stresses than those with PP and fetal (FBP) BP tissues. Collagen fiber orientation along the circumferential axis resulted in lower maximum principal stresses and more uniform and symmetric stress distributions throughout the valve. Conclusions The use of PP and FBP tissue resulted in higher peak stresses than ABP and CBP tissues in the given valve design. Additionally, ensuring collagen fiber orientation along the circumferential axis led to lower maximum stresses felt by the valve leaflets, which could also improve BHV durability.

The development of precision testing for disease diagnosis has advanced medicine by specifically matching patients with drugs to treat specific diseases. High-quality diagnostics start with high-quality tissue specimens. The development and optimization of tissue handling and processing have lagged behind bioassay development. Ultrasound time-of-flight (TOF) technology has been successfully used to monitor the critical processing step of tissue fixation with formalin. In this study, we expand the use of this technology to monitor tissue dehydration and clearing by analyzing TOF signals from 270 different specimens, representing 13 different tissue types obtained through surgical resections. We determined the time constant τ90 for each tissue type for the following tissue processing solvents: 70% ethanol, 90% ethanol, 100% ethanol, and xylene. The TOF signals were correlated with tissue morphology to ensure that high-quality tissue was produced. Tissues can be grouped into those exhibiting fast and slow reagent diffusion. We monitored incomplete dehydration of tissue by skipping a key processing step, dehydration in absolute ethanol, and then correlated the τ90 with poor histomorphology, demonstrating that the technique can detect significant processing errors. Ultrasound TOF technology can therefore be used to monitor all phases of tissue processing cycle and yields an important preanalytical quality metric.

Background and Purpose— Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods— Using data from the Get With The Guidelines–Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results— Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5–15] versus 7 [4–13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P =0.31) and 6.2% versus 5.5% ( P =0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51–1.21]; P =0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52–1.14]; P =0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0–2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P ≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59–0.99]; P =0.04). Conclusions— Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

We report a case of ischemic stroke in an apparently healthy 35-year-old gravida 2 para 1 who was treated with tissue-type plasminogen activator (tPA) 9 hours after vaginal delivery that resulted in severe hemorrhage. Limited data suggest use of thrombolytics in pregnancy is safe, but there is a paucity of evidence assessing their use immediately postpartum. We describe successful combination of tPA with endovascular mechanical thrombectomy (EMT) for treatment of postpartum stroke, which was followed by extensive uterine bleeding.

Tissue plasminogen activator can effectively treat clinical thrombosis in premature infants 11 hours after birth.

Objectives: In Japan, invasive ductal carcinomas, which account for 75% of breast cancer cases, are sub-classified as solid, tubule-forming, scirrhous, and other types based on the histopathological findings. Although time-intensity curve (TIC) analysis of magnetic resonance (MR) images has shown diagnostic ability in differentiating benign and malignant tumors, its ability to diagnose different tumor tissue types has not yet been achieved. In this study, we report a histological classification of invasive ductal carcinoma using the TIC analysis of dynamic MR images of the mammary gland. Material and Methods: A total of 312 invasive ductal carcinomas were analyzed, and each tissue type that indicated malignancy in the washout parts of the tumors was classified and characterized using the TIC. Results: The tissue was classified, and the results were then compared to the pathohistological diagnosis. Using this method, the accuracy of tissue classification by quantitative analysis of TIC-MR images was 86.9% (271/312), which was higher than that obtained by ultrasonography 68.9% (215/312). Conclusion: This method is effective for classifying tissue types in invasive ductal carcinoma.

Objectives: To study the expression and significance of cell cycle proteins CyclinD2, mPGES-1, Bcl2 in diffuse large B-cell lymphoma. Methods: Choose lymphoma and sexually hyperplastic lymphoid tissues as control. Immunohistochemical methods were used to detect the expression of CyclinD2, mPGES-1, and Bcl2, and to compare the positive expression rates of CyclinD2, MPGES-1 and Bcl2 in diffuse large B-cell lymphoma and reactive proliferative lymphoid tissues to compare their diffusion formation. B-cell lymphoma was analyzed for its clinicopathological features. Results: The positive expression rate of CyclinD2, mPGES-1 and Bcl2 in diffuse large B-cell lymphoma is higher than that in reactive proliferative lymphoid tissue, and the difference between the two is statistically significant. There was no statistical difference in CyclinD2, mPGES-1 and Bcl2 in diffuse large B-cell lymphoma between patients according to the age, sex, location, tissue type and degree of differentiation. Conclusion: CyclinD2, mPGES-1 and Bcl2 are highly expressed in patients with diffuse large B-cell lymphoma, and can be used as reference indicators for evaluating the malignant degree and efficacy of dysplasia.

HOXB13, the most posterior HOX B gene, is primarily expressed in the prostate. Using immunohistochemical staining, we evaluated the expression of HOXB13 in prostatic tissues. We found that HOXB13 was expressed in both benign prostatic tissues and prostate adenocarcinoma (AdPCa) but its expression was reduced or lost in neuroendocrine prostate cancer (NEPCa). Additionally, using RNAseq data of HOXs in cell lines derived from various tissue origins, we established HOX codes for these tissue types. We applied the HOX codes to PCa samples and found that the majority of AdPCa samples sustained the prostate-specific HOX code but the majority of NEPCa samples lost it. Our analysis also showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue type. This indicates that NEPCa tumors lose prostate identity but do not gain a clear-cut new tissue identity. Finally, we treated PCa cells with all trans retinoic acid and found that the reduced/lost HOXB13 expression can be reverted, as can AR and AR targets. Taken together, our data indicate that HOXB13 expression is reduced or lost in NEPCa and a loss of prostate-specific HOX code in NEPCa represents a loss of prostatic identity.

Early detection of a tumor makes it more probable that the patient will, finally, beat cancer and recover. The main goal of broadly defined cancer diagnostics is to determine whether a patient has a tumor, where it is located, and its histological type and severity. The major characteristic of the cancer affected tissue is the presence of the glioma cells in the sample. The current approach in diagnosis focuses mainly on microbiological, immunological, and pathological aspects rather than on the “metamaterial geometry” of the diseases. The determination of the effective properties of the biological tissue samples and treating them as disordered metamaterial media has become possible with the development of effective medium approximation techniques. Their advantage lies in their capability to treat the biological tissue samples as metamaterial structures, possessing the well-studied properties. Here, we present, for the first time to our knowledge, the studies on metamaterial properties of biological tissues to identify healthy and cancerous areas in the brain tissue. The results show that the metamaterial properties strongly differ depending on the tissue type, if it is healthy or unhealthy. The obtained effective permittivity values were dependent on various factors, like the amount of different cell types in the sample and their distribution. Based on these findings, the identification of the cancer affected areas based on their effective medium properties was performed. These results prove the metamaterial model capability in recognition of the cancer affected areas. The presented approach can have a significant impact on the development of methodological approaches toward precise identification of pathological tissues and would allow for more effective detection of cancer-related changes.

Background and Purpose— Frequencies of treatment with r-tPA (recombinant tissue-type plasminogen activator) are increasing over the past 15 years. However, published data on the influence of various demographic and clinical factors on r-tPA treatment as well as estimates of future trajectories are limited. We evaluated time trends and future trajectories of r-tPA treatment in patients with acute stroke and the influence of various factors on r-tPA treatment by analyzing data of 103 970 patients enrolled in the Austrian Stroke Unit Registry from 2006 to 2018, of which 18 953 were treated with r-tPA. Methods— Time trends of r-tPA-treatment were investigated in predefined subgroups (minor/major stroke, age, anterior/posterior circulation stroke); limited exponential time series models were calculated to estimate future trends of r-tPA-treatment. Logistic regression models were calculated to estimate the influence of clinical variables on r-tPA-treatment. Results— Overall, r-tPA treatment frequencies increased from 9.9% in 2006 to 21.8% in 2018. We observed a particular increase in patients >80 years, patients presenting with a National Institutes of Health Stroke Scale Score of 2 to 3, patients with posterior circulation stroke, patients with wake-up stroke, and patients without atrial fibrillation. Forecast of overall r-tPA frequencies predicted a further but flattened increase up to 24% by 2025. Logistic regression of time-dependent associations of clinical variables with r-tPA-treatment revealed increasing odds of r-tPA-treatment in patients with a posterior circulation stroke and decreasing odds of r-tPA-treatment in patients with atrial fibrillation. Conclusions— We observed a positive development of r-tPA-treatment frequencies mirroring increasing confidence with intravenous thrombolysis in clinical practice; however, decreasing odds of r-tPA-treatment over time in patients with atrial fibrillation deserve particular attention.

Microscopic examination of tissues or histopathology is one of the diagnostic procedures for detecting colorectal cancer. The pathologist involved in such an examination usually identifies tissue type based on texture analysis, especially focusing on tumour-stroma ratio. In this work, we automate the task of tissue classification within colorectal cancer histology samples using deep transfer learning. We use discriminative fine-tuning with one-cycle-policy and apply structure-preserving colour normalization to boost our results. We also provide visual explanations of the deep neural network’s decision on texture classification. With achieving state-of-the-art test accuracy of 96.2% we also embark on using a deployment friendly architecture called SqueezeNet for memory-limited hardware.

Objective The aim of this study was to perform a detailed analysis of submandibular duct stenoses and propose a classification for them. Study Design This retrospective study covering the period 2001–2019 included 314 patients with 370 submandibular duct stenoses, assessed sialendoscopically for number, grade of narrowing, length, tissue type, and underlying main cause/associated diseases. Results In the included patients, 58.9% of the stenoses were at the papilla, 89.2% were short, and 61.6% were of high grade. Predominantly inflammatory stenoses (type 1) differed from fibrotic stenoses (type 2). Detailed analysis identified stenosis-like lesions caused by anatomic duct narrowing and/or duct variations (type 3), differing significantly from type 2 stenoses in location, length, and bilaterality (each P = .0001) and from type 1 stenoses in location (P = .0001). Compared with type 2, type 1 stenoses were bilateral significantly more often and shorter (each P = .0001). Frequencies of the main causes of stenosis—anatomic narrowness/duct variation and chronic sialadenitis—differed significantly in the different locations (P = .0001). There were no significant differences in frequencies of associated diseases/conditions for the different stenosis types. Conclusions Three types of stenosis/stenosis-like lesions were distinguished. In view of these results and the findings from a review of the literature, the location and type of stenoses were found to be more important parameters, whereas number, grade, and length were less important. The underlying cause may be useful for assessing the prognosis.

Background and Purpose— Data regarding the safety and efficacy of intravenous tPA (tissue-type plasminogen activator) in childhood acute arterial ischemic stroke are inadequate. The TIPS trial (Thrombolysis in Pediatric Stroke; National Institutes of Health grant R01NS065848)—a prospective safety and dose-finding trial of intravenous tPA in acute childhood stroke—was closed for lack of accrual. TIPS sites have subsequently treated children with acute stroke in accordance with established institutional protocols supporting data collection on outcomes. Methods— Data on children treated with intravenous tPA for neuroimaging-confirmed arterial ischemic stroke were collected retrospectively from 16 former TIPS sites to establish preliminary safety data. Participating sites were required to report all children who were treated with intravenous tPA to minimize reporting bias. Symptomatic intracranial hemorrhage (SICH) was defined as ECASS (European Cooperative Acute Stroke Study) II parenchymal hematoma type 2 or any intracranial hemorrhage associated with neurological deterioration within 36 following tPA administration. A Bayesian beta-binomial model for risk of SICH following intravenous tPA was fit using a prior distribution based on the risk level in young adults (1.7%); to test for robustness, the model was also fit with uninformative and conservative priors. Results— Twenty-six children (age range, 1.1–17 years; median, 14 years; 12 boys) with stroke and a median pediatric National Institutes of Health Stroke Scale score of 14 were treated with intravenous tPA within 2 to 4.5 hours (median, 3.0 hours) after stroke onset. No patient had SICH. Two children developed epistaxis. Conclusions— The estimated risk of SICH after tPA in children is 2.1% (95% highest posterior density interval, 0.0%–6.7%; mode, 0.9%). Regardless of prior assumption, there is at least a 98% chance that the risk is

The effects of preanalytical variables in tissue processing and storage periods on RNA quality of tissues have been well documented in each type of cancer. However, few studies have been performed on a comparative assessment of the impacts across different cancer tissues, even though it is well known that RNase activity is highly variable in various tissue types and RNase-rich tissues have been found to yield low-quality RNA.We investigated the impacts of cold ischemia times and long-term storage on RNA integrity in various types of cancer tissue, which had been fresh-frozen and collected at the Samsung Medical Center Biobank. RNA quality was also evaluated with regard to histopathological variables. We analyzed RNA integrity number (RIN) data, which had been obtained from our quality control (QC) processes over the last 7 years. Approximately 2% of samples were randomly selected and processed to measure RIN quarterly and after 6 years of storage for QC purposes.Fresh-frozen tumor tissues yielded high-quality RNA regardless of tumor type and histopathological features. Up to 1-hour cold ischemia times and up to 6-year storage times did not adversely influence RNA integrity. Only 3 samples showed RIN of7 out of a total of 396 analyzed tumor tissues.Tissue quality was not adversely affected by long-term storage or limited variations of cold ischemia times. The low-quality samples could be correlated with the structural composition or intratumoral heterogeneity of tissues. The strict application of standardized protocols for tissue collection is the key for high-quality biobanking.

Cell division is important in human aging and cancer. The estimation of the number of cell divisions (mitotic age) of a given tissue type in individuals is of great interest as it allows not only the study of biological aging (using a new molecular aging target) but also the stratification of prospective cancer risk. Here, we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions. With the MiAge model, the MiAge Calculator was built using the training data of DNA methylation measures of 4,020 tumor and adjacent normal tissue samples from eight TCGA cancer types and was tested using the testing data of DNA methylation measures of 2,221 tumor and adjacent normal tissue samples of five other TCGA cancer types. We showed that within each of the thirteen cancer types studied, the estimated mitotic age is universally accelerated in tumor tissues compared to adjacent normal tissues. Across the thirteen cancer types, we showed that worse cancer survivals are associated with more accelerated mitotic age in tumor tissues. Importantly, we demonstrated the utility of mitotic age by showing that the integration of mitotic age and clinical information leads to improved survival prediction in six out of the thirteen cancer types studied. The MiAge Calculator is available at http://www.columbia.edu/∼sw2206/softwares.htm .

In this paper, we characterize and discriminate between normal and cancer cells from three different tissue types, liver, lung, and breast, using capacitance-voltage-based extracted set of parameters. Cells from each type of cancer cell line were suspended in a liquid media either individually or as mixtures with their normal counterparts. Empirically, normal cells were observed to exhibit higher dielectric constants when compared to cancer cells from the same tissue. Moreover, adding cancer cells to normal cells was observed to increase the capacitance of normal cells, and the extent of this increase varied with the type of tissue tested with the lung cells causing the greatest change. This shows that the cancer cells of different cell origin possess their own signature electrical parameters, especially when compared with their normal counterparts, and that cancer cell seems to affect normal cells in a different manner, depending upon the tissue type. It was also noticed that the cells (both cancer and normal) exhibited a higher dielectric value as per the following order (from least to most): breast, lung, and liver. The changes in electrical parameters from normal to cancer state were explained not only by the modification of its physiological and biochemical properties but also by the morphological changes. This approach paves the way for exploring unique electrical signatures of normal and their corresponding cancer cells to enable their detection and discrimination.

Background and Purpose— Quantitative imaging for the noninvasive assessment of thrombolysis is needed to advance basic and clinical thrombosis-related research and tailor tissue-type plasminogen activator (tPA) treatment for stroke patients. We quantified the evolution of cerebral thromboemboli using fibrin-targeted glycol chitosan–coated gold nanoparticles and microcomputed tomography, with/without tPA therapy. Methods— We injected thrombi into the distal internal carotid artery in mice (n=50). Fifty-five minutes later, we injected fibrin-targeted glycol chitosan–coated gold nanoparticles, and 5 minutes after that, we treated animals with tPA or not (25 mg/kg). We acquired serial microcomputed tomography images for 24 hours posttreatment. Results— Thrombus burden at baseline was 784×10 3 ±59×10 3 μm 2 for the tPA group (n=42) and 655×10 3 ±103×10 3 μm 2 for the saline group (n=8; P =0.37). Thrombus shrinkage began at 0.5 to 1 hour after tPA therapy, with a maximum initial rate of change at 4603±957 μm 2 /min. The rate of change lowered to ≈61% level of the initial in hours 1 to 2, followed by ≈29% and ≈1% in hours 2 to 3 and 3 to 24, respectively. Thus, 85% of total thrombolysis over 24 hours (≈500 μm 2 , equivalent to 64% of the baseline thrombus burden) occurred within the first 3 hours of treatment. Thrombus burden at 24 hours could be predicted at around 1.5 to 2 hours. Saline treatment was not associated with significant changes in the thrombus burden. Infarct size was smaller in the tPA group versus saline group (18.1±2.3 versus 45.8±3.3 mm 2 ; P r =0.71; P Conclusions— Thromboembolic burden and the efficacy of tPA therapy can be assessed serially, noninvasively, and quantitatively using high-resolution microcomputed tomography and a fibrin-binding nanoparticle imaging agent.

Objective. To examine the effect of different tissue type of neurotransplantation on the locomotor function restoration after experimental spinal cord injury. Materials and methods. Animals: inbred albino male rats ( 5.5 months, 300 g ); experimental groups: 1 — spinal cord injury + immediate homotopical transplantation of olfactory bulb tissue (TOBT, n=34), 2 — spinal cord injury + analogous transplantation of fetal (E18) cerebellum tissue (TFСT, n=15), 3 — spinal cord injury + analogous transplantation of fetal (E18) kidney tissue (TFKT, n=8 ), 4 — spinal cord injury only in similar (control–1, n=16) and different (control–2, n=40) experimental seasons. Model of injury — left-side spinal cord hemisection at Т XI level; monitoring the ipsilateral hindlimb function indicator (IHL FI) — the Вasso–Вeattie–Вresnahan scale (BBB). Results. The predominance (p> 0.05) of the IHL FI after approved types of neurotransplantation has been noted when comparing with the control group–1 — at the 1 st –5 th week (ТОBT), 1 st –2 nd and 6 th –7 th week (TFСT), and at the end of the 8 th week (TFKT); when comparing with the control group–2 — at the 1 st –3 rd (ТОBT) and 1 st (TFСT) week of the experiment. The maximum value of the IHL FI has been observed at the 2 nd (ТОBT, 3,7±0,5 points ВВВ), 1 st , 6 th –7 th (TFСT, 3,6±0,8 points ВВВ), 12 th and 20 th (TFKT, 3,6±1,2 points ВВВ) weeks, minimum value of the IHL FI — at the 24 th (ТОBT, 2,4±0,6 points ВВВ), 3 rd (TFСT, 3,0±0,9 points ВВВ) and 1 st (TFKT, 1,9±1,1 points ВВВ) week of the experiment. Average IHL FI values of the three experimental groups at the 24 th week of the experiment have been amounted to 2,4–3,3 points BBB and comprised in a range of control groups final mean values (1,6–3,4 балла ВВВ). Significant differences between the IHL FI values of the groups ТОBT, TFСT and TFKT have not been observed during the experiment. In the case of TOBT significant changes of IHL FI have been noted during the 2 nd (increase), 6 th –7 th and 16 th –24 th week (reduced to a level below the 1 st week); in the case of TFKT — at the 1 st –3 rd week (increase); in the case of TFСT no significant changes have been identified. A common feature of the dynamics of the three experimental groups is prevalence of IHL FI values over the control during the first few weeks and lack of progression during further period of observation, that can be interpreted in a view of angiogenic, neurotropic, proinflammatory and mediator effects of the grafts. Conclusion. Approved types of neurotransplantation provide a temporary effect, continuing during the first month of the traumatic process; the study of the pathophysiological mechanisms of this effect can significantly improve understanding of tissue processes after multicomponent neuroengineering interventions.

Background and Purpose— We investigated whether administration of edaravone, a free radical scavenger, before or during tissue-type plasminogen activator (tPA) can enhance early recanalization in a major arterial occlusion. Methods— The YAMATO study (Tissue-Type Plasminogen Activator and Edaravone Combination Therapy) is an investigator-initiated, multicenter (17 hospitals in Japan), prospective, randomized, and open-label study. Patients with stroke secondary to occlusion of the M1 or M2 portion of the middle cerebral artery and within 4.5 hours of the onset were studied. The subjects were randomly allocated to the early group (intravenous edaravone [30 mg] was started before or during tPA) and the late group (edaravone was started after tPA and the assessment of early recanalization). Results— One-hundred sixty-five patients (96 men; median age [interquartile range], of 78 [69–85] years) were randomized 1:1 to either the early group (82 patients) or the late group (83 patients). Primary outcome, defined as an early recanalization 1.5 hour after tPA, was observed in 53% of the early group and in 53% of the late group ( P =1.000). About secondary outcomes, the rate of significant recanalization of ≥50% was not different between the 2 groups (28% versus 34%; P =0.393). The symptomatic intracerebral hemorrhage has occurred in 4 patients (5%) in the early group and in 2 patients (2%) in the late group ( P =0.443). The favorable outcome (modified Rankin Scale score of 0–2) at 3 months was also similar between the groups (53% versus 57%; P =0.738). Conclusions— The timing of edaravone infusion does not affect the rate of early recanalization, symptomatic intracerebral hemorrhage, or favorable outcome after tPA therapy. Clinical Trial Registration— URL: http://www.umin.ac.jp/ctr/index-j.htm . Unique identifier: UMIN000006330.

Background and Purpose— There is uncertainty among many emergency medicine physicians about the decision to give intravenous tPA (tissue-type plasminogen activator), which limits its use. A checklist approach has been suggested as a solution. We compared agreement on tPA treatment in suspected acute ischemic stroke patients between emergency medicine residents (EMRs) using a checklist and vascular neurology fellows (VNFs). Methods— Every suspected acute stroke patient brought to our comprehensive stroke center emergency room within 4.5 hours from symptom onset was prospectively evaluated simultaneously and independently by VNFs and EMRs. The latter used a tPA screening checklist, which included guideline exclusion criteria to help with their treatment decision. Agreement was determined using kappa (k) statistics. Results— Over 6 months, 60 patients were enrolled; 10% large vessel atherosclerosis, 18% cardioembolism, 12% small vessel, 12% cryptogenic, and 47% mimic. Forty-two percent were deemed tPA eligible by the EMR, 30% by the VNF, and 37% by the vascular neurology faculty. There were no complications in any tPA-treated patients. Agreement was substantial between EMR and VNF (κ=0.68 [95% CI, 0.49–0.87]) and between EMR and vascular neurology faculty (κ=0.69 [95% CI, 0.50–0.87]). Stroke mimics were the main cause of disagreement between EMR and VNF (κ=0.24 [95% CI, −0.15 to 0.63]) and between EMR and vascular neurology faculty (κ=0.35 [95% CI, −0.08 to 0.78]). Conclusions— Our data suggest that with the aid of a checklist, EMRs can accurately treat stroke patients with tPA. Areas for improvement include recognition of stroke mimics. Further studies are warranted to evaluate checklist-enhanced tPA treatment to allay emergency medicine physician uncertainty and expand the use of tPA.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial due to safety concerns. However, there are few data on use of intravenous tissue plasminogen activator (tPA) and symptomatic intracranial hemorrhage (sICH) or outcomes in this population. METHODS: Using data from the Get With The Guidelines-Stroke Registry (GWTG-Stroke) between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among AIS patients treated with tPA within the 3–4.5 hour window who had a history of prior stroke and DM (HxS+DM, n=2129) versus those without either history (n=16,690). RESULTS: Compared with patients without either history, those with both prior stroke and DM treated with tPA after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of prior stroke, diabetes, and more severe stroke (NIHSS median 8 [IQR 5–15] vs. 7 [4–13]). The unadjusted rates of sICH and in-hospital mortality were 4.3% (HxS+DM) vs 3.8% (without either history) (p=0.31) and 6.2% vs 5.5% (p=0.20), respectively. These differences were not statistically significant after risk adjustment (sICH, adjusted odds ratio [OR] 0.79[95% CI, 0.51–1.21], p=0.28; in-hospital mortality OR 0.77 [95% CI, 0.52–1.14], p=0.19). Unadjusted rate of functional independence (Modified Rankin Scale score [mRS] 0–2) at discharge was lower in those with history of prior stroke and DM (30.9% HxS+DM vs 44.8% without either history, p=

Breast cancer is a heterogeneous disease with different prognoses and responses to systemic treatment depending on its molecular characteristics, which makes it imperative to develop new biomarkers for an individualized diagnosis and personalized oncological treatment. Ex vivo high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H MRS) is the most common technique for metabolic quantification in human surgical and biopsy tissue specimens. To perform a review of the current available literature on the clinical applications of HRMAS 1H MRS metabolic analysis in tissue samples of breast cancer patients. This systematic scoping review included original research papers published in the English language in peer-reviewed journals. Study selection was performed independently by two reviewers and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were followed. The literature search returned 159 studies and 26 papers were included as part of this systematic review. There was considerable variation regarding tissue type, aims, and statistical analysis methods across the different studies. To facilitate the interpretation of the results, the included studies were grouped according to their aims or main outcomes into: feasibility and tumor diagnosis (n = 6); tumor heterogeneity (n = 2); correlation with proteomics/transcriptomics (n = 3); correlation with prognostic factors (n = 11); and response evaluation to NAC (n = 4). There is a lot of potential in including metabolic information of breast cancer tissue obtained with HRMAS 1H MRS. To date, studies show that metabolic concentrations quantified by this technique can be related to the diagnosis, prognosis, and treatment response in breast cancer patients.

Optical Coherence Tomography (OCT) is nowadays being widely employed as a diagnostic tool for skin cancer. It can produce feedback on tissue morphology alterations produced by different pathologies. OCT images are mainly produced by differences in refractive index and attenuation coefficient, providing in-depth information. Intensity OCT images display the effect of tissue alterations on backscattered light, but it does not represent real physical magnitude. In a number of occasions, morphology alteration events within the same tissue type, produce intensity variations in OCT images that can be misclassified as different tissue component. The estimation of depth-resolved attenuation coefficient improves tissue contrast, helping to identify tissue identity and isolating the effect of disordered structures of the same tissue. The proposed methodology shows that melanoma and Basal Cell Carcinoma (BCC) pathologies exhibit different optical parameters in depth. This enhances the identification of subsurface skin features. This research was funded FIS2010-19860 (DA2TOI), TEC2016-76021-C2-2-R (SENSA), DTS17-00055 (FUSIODERM), INNVAL 16/02 (DICUTEN), INNVAL 18/23 (DAPATOO) and co-funded with FEDER funds. This work has been developed thanks to the collaboration of the members of Dermatology Service at Marqués de Valdecilla University Hospital.

A major approach to cancer research in the late twentieth century was to search for genes that, when altered, initiated the development of a cell into a cancerous state (oncogenes) or failed to stop this development (tumor suppressor genes). But as researchers acquired the capacity to sequence tumors and incorporated the resulting data into databases, it became apparent that for many tumors no genes were frequently altered and that the genes altered in different tumors in the same tissue type were often distinct. To address this heterogeneity problem, many researchers looked to a higher level of organization-to mechanisms in which gene products (proteins) participated. They proposed to reduce heterogeneity by recognizing that multiple gene alterations affect the same mechanism and that it is the altered mechanism that is responsible for the cell developing one or more hallmarks of cancer. I examine how mechanisms figure in this research and focus on two heuristics researchers use to integrate proteins into mechanisms, one focusing on pathways and one focusing on clusters in networks.

Chrysomya megacephala Fabricius is one of the most common myiasis-causing and carrion-feeding fly species in the tropics. This species has a worldwide distribution due to globalization and therefore is of critical importance to the public health sector and forensic investigations. Development studies carried worldwide show that Ch. megacephala reared at similar temperatures may require different amounts of time to complete their cycle of growth. The present study determined for the first time the life-history information of this species in Sri Lanka. Chrysomya megacephala colonies were reared on three different food sources (bovine muscle, swine muscle, and swine liver) considering the most common forensic entomology rearing mediums and the capability of Ch. megacephala to cause myiasis in cattle. Furthermore, colonies were reared at four temperature regimes representing several specific development conditions of this blowfly: 1) 20°C representing the estimation of the lower developmental threshold for this species in Sri Lanka; 2) 25 and 27°C representing typical room/environmental temperatures in Sri Lanka; and 3) 38°C as this is the typical living animal temperature, representing myiasis conditions. Results show that temperature significantly affected larval length and width over time; however, tissue type was not a significant factor. The fastest development was recorded at 38°C for immature feeding on bovine muscle (162.15 h), followed by those fed swine liver (184.15 h) and swine muscle (208.00 h). The calculated minimum temperature threshold for Ch. megacephala was 13°C. Data generated will be crucial for future forensic investigations involving living or deceased individuals colonized by this species.

Purpose Subepithelial connective tissue grafts (SCTGs) are commonly performed for the treatment of gingival recession due to their high predictability. This study evaluated and histologically compared connective tissue grafts in terms of the presence of epithelial remnants and composition of the tissue types that were present (epithelium, lamina propria, and submucosa). Methods Ten patients underwent epithelium removal using 2 different techniques: the use of a blade (group B) and through abrasion (group A). Twenty samples were collected and each tissue type was analyzed histologically in terms of its area, thickness, and proportion of the total area of the graft. Results In 4 samples (40%) from group B (n=10) and 2 samples (20%) from group A (n=10), the presence of an epithelial remnant was observed, but the difference between the groups was not statistically significant (P>0.05). Likewise, no statistically significant differences were observed between the groups regarding the area, mean thickness, or proportion of the total area for any of the tissue types (P>0.05). Conclusions Histologically, SCTGs did not show statistically significant differences in terms of their tissue composition depending on whether they were separated from the epithelial tissue by abrasion or by using a blade., Graphical Abstract

Plasmin(ogen) acquisition is critical for invasive disease initiation by Streptococcus pyogenes (GAS). Host urokinase plasminogen activator (uPA) plays a role in mediating plasminogen activation for GAS dissemination, however the contribution of tissue-type plasminogen activator (tPA) to GAS virulence is unknown. Using novel tPA-deficient ALBPLG1 mice, our study revealed no difference in mouse survival, bacterial dissemination or the pathology of GAS infection in the absence of tPA in AlbPLG1/tPA(−/−) mice compared to AlbPLG1 mice. This study suggests that tPA has a limited role in this humanized model of GAS infection, further highlighting the importance of its counterpart uPA in GAS disease.

Ruptured hepatic tumors are a rare but potentially fatal clinical presentation. The most commonly ruptured benign and malignant hepatic tumors are hepatic adenoma and hepatocellular carcinoma, respectively. Acute management focuses on control of bleeding usually through transcatheter embolization. Definitive management is based on the patient’s clinical condition and tissue type.

Tauopathies is a class of neurodegenerative disorders which involves the transformation of physiological tau into pathogenic tau. One of the prime causes reported to drive this conversion is tau hyperphosphorylation and the subsequent propagation of pathogenic protein aggregates across the nervous system. Although past attempts have been made to deduce the details of tau propagation, yet not much is known about its mechanism. A better understanding of this aspect of disease pathology can prove to be beneficial for the development of diagnostic and therapeutic approaches. In our work, we utilize the plethora of advantages procured byDrosophilato introduce a novelin-vivotauopathy propagation model. For the first time, we demonstrate that the human tau (h-tau) possesses an intrinsic property to spread trans-cellularly in the fly nervous system irrespective of the tau allele or the neuronal tissue type. Aggregate migration restricted by targeted down-regulation of a specific kinase, elucidates the role of hyper-phosphorylation in its movement. On the contrary to the previous models, the present system enables a rapid, convenient and robustin-vivostudy of tau migration pathology. Henceforth, the developed model would not only be immensely helpful in uncovering the mechanistic in-depths of tau propagation pathology but also aid in modifier and/or drug screening for amelioration of tauopathies.

Brain bioenergetic abnormalities have been observed frequently in adults with major depressive disorder (MDD); however, results have been inconsistent regarding whether decreased or increased metabolism was observed. Phosphorus-31 magnetic resonance spectroscopy (31P MRS) allows for the quantification of bioenergetic molecules, containing high-energy phosphates, over the whole brain as well as measuring the differences between gray matter and white matter. We recruited 50 subjects with a current diagnosis of MDD, not currently treated with psychotropic medication, between ages of 18 and 65 (mean±SD age: 43.4±13.6; 46% female) and 30 healthy volunteers, matched for age and gender (39.0±12.5 years of age; 36.6% female). All subjects received a T1 MP-FLASH scan for tissue segmentation followed by 31P MRS, chemical shift imaging scan with 84 voxels of data collected over the entire brain utilizing a dual-tuned, proton-phosphorus coil to minimize subject movement. Phosphocreatine and inorganic phosphate (Pi) varied in opposite directions across gray matter and white matter when MDD subjects were compared with controls. This finding suggests alterations in high-energy phosphate metabolism and regulation of oxidative phosphorylation in MDD patients. In addition, within the MDD group, gray matter Pi, a regulator of oxidative phosphorylation, correlated positively with severity of depression. These data support a model that includes changes in brain bioenergetic function in subjects with major depression.

We experienced the giant seminoma with 18×10×10cm sized and about 2.6kg weight of 25year old patient. We intensively examined the histological tissue type distributions in this giant seminoma. Most of the tumor consisted of seminoma components. In addition, the tumor included the very small fragments of yolk sac tumor and embryonal carcinoma component at the root part of the seminoma mass. This shows that intensive histological examination may contribute to the finding of other embryonic component of the large seminoma. This may show that leaving the seminoma growing may generate the other embryonic tumor component, not always big enough to find out in a routine procedure, during the growth, in the different way from the original mixed cell germ tumor.

Objective: A randomised controlled trial to compare negative pressure wound therapy (NPWT) using our innovative negative pressure device (NPD) and the standard pressure ulcer (PU) wound dressing of in traumatic paraplegia patients. Method: This study was conducted in the Department of Orthopaedic Surgery at King George's Medical University, Lucknow, India. Traumatic paraplegia patients with sacral pressure ulcers of stage 3 and 4 were randomised into two groups, receiving either standard wound dressings or NPWT with NPD. The outcomes monitored were length, width (surface area), depth of PU, exudates, discharge, tissue type (necrotic, slough and red granulating tissue), and cost-effectiveness during 0 to 9 weeks follow-up. Results: Length and width were significantly (pConclusion: Our NPD is better than standard wound care procedures and cost-effective for management of PU.

espanolLa monitorizacion no invasiva es uno de los elementos claves para analizar la activacion del fotosensibilizador durante el proceso fotoquimico subyacente a la Terapia Fotodinamica (TFD) mediante su fluorescencia. Esta ultima se puede emplear tambien para discriminar el tejido patologico del sano. En este trabajo se analizan los patrones de fluorescencia superficial en tres tipos diferentes de cancer de piel no melanoma, asi como su respuesta al tratamiento fotodinamico, mediante un modelo dosimetrico para TFD con MAL-PpIX. Los resultados obtenidos muestran diferencias incluso mayores del 50% en los patrones de fluorescencia a medida que progresa el tratamiento dependiendo del tipo de tejido maligno. Lo que demuestra la gran relevancia del medio biologico como factor dosimetrico adicional en el contexto fotodinamico. Estos resultados contribuyen al futuro de desarrollo de una terapia personalizada asistida mediante herramientas dosimetricas para interpretar las imagenes de fluorescencia obtenidas durante la monitorizacion del tratamiento y el fotodiagnostico diferencial. EnglishNon-invasive treatment monitoring is one of the key elements to assess the photosensitizer activation during the photochemical process underlying Photodynamic Therapy (TFD) by its fluorescence. Furthermore the photosensitizer fluorescence can be employed to discriminate the pathological tissue from the healthy one. In this work the superficial fluorescence patterns in three different types of nonmelanoma skin cancer tumors and their photodynamic treatment response are analysed by a fluorescence based dosimetric model for PDT with topical MAL-PpIX. Results show differences of even more than 50% in the fluorescence patterns as the treatment progresses depending on the malignant tissue type. They demonstrate the great relevance of the biological media as an additional dosimetric factor within the photodynamic context. These results contribute to the development of a future customized therapy with the assistance of dosimetric tools to interpret the fluorescence images obtained during the treatment monitoring as well as in differential photodiagnosis.

Purpose: As we have published expertise in breast cancer xenograft models and clonal dynamics, our aim was to explore rates of engraftment based on type of tissue for attempted xenografting (primary vs relapsed/metastatic disease) and clinical breast biomarker subtype. Methods: Tissue from patients (pts) enrolled in a locally advanced/metastatic study and a breast tumour tissue repository (ie. resectable primaries) between Sept. 2008 and July 2015 underwent xenografting using NodScid/IL2rgKO (NSG) mice. Xenografts were passaged when tumour volume reached 1 cm3. Mice with no engraftment after 12 months (mos) were sacrificed. Pt charts were reviewed to determine biomarker status (hormone receptor [HR], HER2), date and type of tissue collection for xenografting. Prediction of successful engraftment based on tissue type and biomarker status was performed using nominal logistic regression. Results: A total of 70 tissue samples with known engraftment status were included in the analysis: 51 from primary breast tumour, 10 from relapsed disease (dz) with ≤ 1 line of therapy in the advanced setting and 9 from relapsed dz with > 1 line of therapy in the advanced setting. Tumours from pts treated with > 1 line of therapy were more likely to engraft compared to primary or recurrent dz with ≤ 1 line of therapy (89%, 35%, and 40% respectively; p=.008). HR- primary tumours were more likely to engraft compared to HR+ primary tumours: 71% of HR-/HER2- (triple negative) and 67% of HR-/HER2+ tumours versus 4% of HR+/HER2- and 38% of HR+/HER2+ tumours; p Conclusion: This preliminary study highlights potential differences in successful xenoengraftment based on biomarker status at diagnosis and type of tissue, primary vs relapsed tumour, the latter suggesting that the underlying biology of primary or first relapsed recurrent disease is distinct from more refractory disease, and warrants further exploration. This work is ongoing. (Funded by CBCRA, BCCF) Engraftment of primary tumour vs relapsed disease Primary tumour (N=52) N, (%)Recurrent disease and ≤ 1 line of Rx in advanced setting (N=10) N, (%)Recurrent disease and > 1 line of Rx in advanced setting (N=9) N, (%)Engraftment Yes18 (35)4 (40)8 (89)HR-/HER2-10 (55)1 (25)2 (25)HR-/HER2+4 (22)1 (25)1 (13)HR+/HER2+3 (17)00HR+/HER2-1 (6)2 (50)5 (62)Engraftment No33 (65)6 (60)1 (11)HR-/HER2-4 (12)00HR-/HER2+2 (6)1 (17)0HR+/HER2+5 (15)00HR+/HER2-22 (67)5 (83)1 (100) Citation Format: den Brok W-l, Chia S, Kalloger S, Bates C, Aparicio S, Mar C, Gelmon K, Eirew P. Rates of successful engraftment in breast cancer xenograft models based on tissue type: Primary vs relapsed disease [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-06-10.

Background and Purpose— The aim of this study is to determine agreement among vascular neurology fellows and faculty in treating patients with acute ischemic stroke with intravenous tissue-type plasminogen activator and intra-arterial thrombectomy (IAT). Methods— Patients were evaluated simultaneously by at least 2 vascular neurology. Agreement was determined using kappa (κ) and intraclass correlation coefficients. Results— In 60 patients, agreement was substantial for tissue-type plasminogen activator (κ=0.75 [95% confidence interval, 0.57–0.92]) and IAT (κ=0.63 [95% confidence interval, 0.30–0.96]), with no difference between fellow–fellow versus fellow–faculty. Intraclass correlation coefficient for National Institutes of Health Stroke Scale was 0.94 (95% confidence interval, 0.90–0.97) and κ for Alberta Stroke Program Early CT Score was 0.53 (95% confidence interval, 0.20–0.78). Rapidly improving or mild deficits caused disagreement for both tissue-type plasminogen activator and IAT, whereas interpretation of computed tomographic perfusion led to disagreement for IAT. Conclusions— We found substantial agreement between vascular neurology fellows and faculty in treating with tissue-type plasminogen activator or IAT. Areas for improvement include recognition of stroke mimics, consensus on treating less severe strokes, and use/interpretation of imaging.