We related composition of cerebral thrombi to stroke subtype and attenuation on non-contrast CT (NCCT) to gain more insight in etiopathogenesis and to validate thrombus attenuation as a new imaging ...biomarker for acute stroke.
We histopathologically investigated 22 thrombi retrieved after mechanical thrombectomy in acute stroke patients. First, thrombi were classified as fresh, lytic or organized. Second, percentages of red blood cells (RBCs), platelets and fibrin and number of red, white (respectively RBCs or platelets outnumbering other components with ≥ 15%) or mixed thrombi were compared between large artery atherosclerosis (LAA), cardioembolism, dissection and unknown subtype. Third, correlation between attenuation and RBCs, platelets and fibrin was calculated using Pearson's correlation coefficients (r).
Thrombi were fresh in 73% (n = 16), lytic in 18% (n = 4) and organized in 9% (n = 2). The stroke cause was LAA in eight (36%), cardioembolism in six (27%), dissection in three (14%), and unknown in five (23%) patients. LAA thrombi showed the highest percentage RBCs (median 50 (range 35-90)), followed by dissection (35 (20-40), p = 0.05), cardioembolism (35 (5-45), p = 0.013) and unknown subtype (25 (2-40), p = 0.006). No differences in platelets (p = 0.16) and fibrin (p = 0.52) between subtypes were found. LAA thrombi were classified as red or mixed (both n = 4), cardioembolisms as mixed (n = 5) or white (n = 1) and dissection as mixed (n = 3). There was a moderate positive correlation between attenuation and RBCs (r = 0.401, p = 0.049), and weak negative correlations with platelets (r = -0.368, p = 0.09) and fibrin (r = -0.073, p = 0.75).
The majority of cerebral thrombi is fresh. There are no differences in age of thrombi between subtypes. LAA thrombi have highest percentages RBCs, cardioembolism and unknown subtype lowest. No relationship exists between subtype and platelets or fibrin percentages. We found a correlation between the RBC-component and thrombus attenuation, which improves validation of thrombus attenuation on NCCT as an imaging biomarker for stroke management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Guidelines advise multiparametric magnetic resonance imaging (mpMRI) before repeat biopsy in patients with negative systematic biopsy (SB) and a suspicion of prostate cancer (PCa), enabling MRI ...targeted biopsy (TB). No consensus exists regarding which of the three available techniques of TB should be preferred.
To compare detection rates of overall PCa and clinically significant PCa (csPCa) for the three MRI-based TB techniques.
Multicenter randomised controlled trial, including 665 men with prior negative SB and a persistent suspicion of PCa, conducted between 2014 and 2017 in two nonacademic teaching hospitals and an academic hospital.
All patients underwent 3-T mpMRI evaluated with Prostate Imaging Reporting and Data System (PIRADS) version 2. If imaging demonstrated PIRADS ≥3 lesions, patients were randomised 1:1:1 for one TB technique: MRI-transrectal ultrasound (TRUS) fusion TB (FUS-TB), cognitive registration TRUS TB (COG-TB), or in-bore MRI TB (MRI-TB).
Primary (overall PCa detection) and secondary (csPCa detection Gleason score ≥3+4) outcomes were compared using Pearson chi-square test.
On mpMRI, 234/665 (35%) patients had PIRADS ≥3 lesions and underwent TB. There were no significant differences in the detection rates of overall PCa (FUS-TB 49%, COG-TB 44%, MRI-TB 55%, p=0.4). PCa detection rate differences were −5% between FUS-TB and MRI-TB (p=0.5, 95% confidence interval CI −21% to 11%), 6% between FUS-TB and COG-TB (p=0.5, 95% CI −10% to 21%), and −11% between COG-TB and MRI-TB (p=0.17, 95% CI −26% to 5%). There were no significant differences in the detection rates of csPCa (FUS-TB 34%, COG-TB 33%, MRI-TB 33%, p>0.9). Differences in csPCa detection rates were 2% between FUS-TB and MRI-TB (p=0.8, 95% CI −13% to 16%), 1% between FUS-TB and COG-TB (p>0.9, 95% CI −14% to 16%), and 1% between COG-TB and MRI-TB (p>0.9, 95% CI −14% to 16%). The main study limitation was a low rate of PIRADS ≥3 lesions on mpMRI, causing underpowering for primary outcome.
We found no significant differences in the detection rates of (cs)PCa among the three MRI-based TB techniques.
In this study, we compared the detection rates of (aggressive) prostate cancer among men with prior negative biopsies and a persistent suspicion of cancer using three different techniques of targeted biopsy based on magnetic resonance imaging. We found no significant differences in the detection rates of (aggressive) prostate cancer among the three techniques.
In a repeat biopsy setting, multiparametric magnetic resonance imaging (mpMRI)-based targeted biopsy has a high detection rate of (clinically significant) prostate cancer. There were no significant differences in the detection rates of (clinically significant) prostate cancer among three techniques of mpMRI-based targeted biopsy.
•New rare earth carboxylate corrosion inhibitor complexes evaluated.•Reduced corrosion on mild steel in 0.01 M NaCl.•Performance dependent on rare earth type, with yttrium proving most ...effective.•Surface analysis shows the presence of a film containing inhibitor components.
Four recently synthesized rare earth 3-(4-methylbenzoyl)propanoate (mbp) compounds (RE = La, Ce, Nd and Y) were evaluated as corrosion inhibitors for mild steel in 0.01 M NaCl. At a concentration of 0.25 mM all the compounds showed some level of inhibition after 30 min immersion, with the Y(mbp)3 complex giving the largest reduction in corrosion current density, from 1.92 μA/cm2 for the control sample to 0.25 μA/cm2 for the Y based inhibitor. All the RE(mbp)3 inhibitors acted predominantly as anodic inhibitors, showing little effect on the cathodic reaction after 30 min. Surface analysis after 6 h immersion using FTIR and EDS detected the presence of a thin film containing inhibitor components on all surfaces, thus accounting for the reduced corrosion rate, with the Y(mbp)3 compound having the most significant effect on corrosion and showing the most uniform surface coverage.
Prospective validation of
Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the ...diagnostic accuracy of
Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer.
Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection
Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported.
A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%).
In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement
Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.
Identification of patients at risk for primary and secondary manifestations of atherosclerotic disease progression is based mainly on established risk factors. The atherosclerotic plaque composition ...is thought to be an important determinant of acute cardiovascular events, but no prospective studies have been performed. The objective of the present study was to investigate whether atherosclerotic plaque composition is associated with the occurrence of future vascular events.
Atherosclerotic carotid lesions were collected from patients who underwent carotid endarterectomy and were subjected to histological examination. Patients underwent clinical follow-up yearly, up to 3 years after carotid endarterectomy. The primary outcome was defined as the composite of a vascular event (vascular death, nonfatal stroke, nonfatal myocardial infarction) and vascular intervention. The cumulative event rate at 1-, 2-, and 3-year follow-up was expressed by Kaplan-Meier estimates, and Cox proportional hazards regression analyses were performed to assess the independence of histological characteristics from general cardiovascular risk factors. During a mean follow-up of 2.3 years, 196 of 818 patients (24%) reached the primary outcome. Patients whose excised carotid plaque revealed plaque hemorrhage or marked intraplaque vessel formation demonstrated an increased risk of primary outcome (risk difference=30.6% versus 17.2%; hazard ratio HR with 95% confidence interval=1.7 1.2 to 2.5; and risk difference=30.0% versus 23.8%; HR=1.4 1.1 to 1.9, respectively). Macrophage infiltration (HR=1.1 0.8 to 1.5), large lipid core (HR=1.1 0.7 to 1.6), calcifications (HR=1.1 0.8 to 1.5), collagen (HR=0.9 0.7 to 1.3), and smooth muscle cell infiltration (HR=1.3 0.9 to 1.8) were not associated with clinical outcome. Local plaque hemorrhage and increased intraplaque vessel formation were independently related to clinical outcome and were independent of clinical risk factors and medication use.
The local atherosclerotic plaque composition in patients undergoing carotid endarterectomy is an independent predictor of future cardiovascular events.
Interleukin 17-antagonist secukinumab demonstrated high efficacy for treatment of psoriasis in randomized controlled trials. However, performance in daily practice may differ from trials. Drug ...survival is a comprehensive outcome covering effectiveness and safety, suitable for analyses of daily practice. The aim of this study was to evaluate drug survival of secukinumab in a daily practice psoriasis cohort. Data were collected from 13 hospitals. Drug survival was analysed using Kaplan-Meier survival curves, split for reason of discontinuation. In total, 196 patients were included (83% biologic experienced). Overall, 12 and 18 months drug survival of secukinumab was 76% and 67%, respectively, and was mostly determined by ineffectiveness. There was a trend towards shorter drug survival in women and in biologic experienced patients. Thirteen percent of patients experienced at least one episode of fungal infection. This is one of the first studies of drug survival of secukinumab in patients with psoriasis treated in daily practice.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objectives
To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow‐up in patients with negative systematic biopsy (SB) followed by non‐suspicious ...multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population.
Patients and Methods
A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate‐specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging‐Reporting and Data System (PI‐RADS) ≤2 on mpMRI entered biochemical follow‐up. Follow‐up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow‐up compared to the expected number in the general population (standardized incidence ratio SIR).
Results
In total, 431 patients had non‐suspicious mpMRI and entered biochemical follow‐up. After a median (interquartile range) follow‐up of 41 (23–57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3–7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI‐RADS ≥3) were significant predictive factors for csPCa.
Conclusion
After negative prior biopsy and non‐suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image‐guided risk‐adapted diagnostic surveillance strategies is warranted.
Molecular subtyping of breast cancer by gene expression has proven its significance in females. Immunohistochemical surrogates have been used for this classification, because gene expression ...profiling is not yet routinely feasible. Male breast cancer is rare and large series are lacking. In this study, we used immunohistochemistry for molecular subtyping of male breast cancer. A total of 134 cases of male breast cancer were immunohistochemically stained on tissue microarrays for estrogen receptor (ER), progesterone receptor (PR), HER2 and epidermal growth factor receptor (EGFR), as well as for CK5/6, CK14, and Ki67. HER2 was also assessed by chromogen in situ hybridization. Cases were classified as luminal A (ER+ and/or PR+, and HER2- and Ki67 low), luminal B (ER+ and/or PR+, and HER2+ or Ki67 high), HER2 driven (ER-, PR-, HER2+), basal-like (ER-, PR-, HER2-, CK5/6+ and/or CK14+ and/or EGFR+), or unclassifiable triple-negative (negative for all six markers). Luminal type A was by far the most encountered type of male breast cancers, representing 75% of the cases. Luminal type B was seen in 21% and the remaining 4% of cases were classified as basal-like (n=4) and unclassifiable triple-negative (n=1). No HER2 driven cases were identified. Patients with basal-like cancer were significantly younger (P=0.034). Luminal B type cancers showed significantly higher histological grade (P<0.001), mitotic index (P<0.001), and PR negativity (P=0.005) compared with luminal type A cancers. In conclusion, most male breast cancers are luminal A and luminal B types, whereas basal-like, unclassifiable triple-negative, and HER2 driven male breast cancers are rare. Luminal type B seem to represent a subtype with an aggressive phenotype. This distribution of molecular subtypes in male breast cancer is clearly different compared with female breast cancers, pointing to possible important differences in carcinogenesis.
Molecular pathology is becoming more and more important in present day pathology. A major challenge for any molecular test is its ability to reliably detect mutations in samples consisting of ...mixtures of tumor cells and normal cells, especially when the tumor content is low. The minimum percentage of tumor cells required to detect genetic abnormalities is a major variable. Information on tumor cell percentage is essential for a correct interpretation of the result. In daily practice, the percentage of tumor cells is estimated by pathologists on hematoxylin and eosin (H&E)-stained slides, the reliability of which has been questioned. This study aimed to determine the reliability of estimated tumor cell percentages in tissue samples by pathologists. On 47 H&E-stained slides of lung tumors a tumor area was marked. The percentage of tumor cells within this area was estimated independently by nine pathologists, using categories of 0–5%, 6–10%, 11–20%, 21–30%, and so on, until 91–100%. As gold standard, the percentage of tumor cells was counted manually. On average, the range between the lowest and the highest estimate per sample was 6.3 categories. In 33% of estimates, the deviation from the gold standard was at least three categories. The mean absolute deviation was 2.0 categories (range between observers 1.5–3.1 categories). There was a significant difference between the observers (P<0.001). If 20% of tumor cells were considered the lower limit to detect a mutation, samples with an insufficient tumor cell percentage (<20%) would have been estimated to contain enough tumor cells in 27/72 (38%) observations, possibly causing false negative results. In conclusion, estimates of tumor cell percentages on H&E-stained slides are not accurate, which could result in misinterpretation of test results. Reliability could possibly be improved by using a training set with feedback.
Polyploidization is observed in all mammalian species and is a characteristic feature of hepatocytes, but its molecular mechanism and biological significance are unknown. Hepatocyte polyploidization ...in rodents occurs through incomplete cytokinesis, starts after weaning and increases with age. Here, we show in mice that atypical E2F8 is induced after weaning and required for hepatocyte binucleation and polyploidization. A deficiency in E2f8 led to an increase in the expression level of E2F target genes promoting cytokinesis and thereby preventing polyploidization. In contrast, loss of E2f1 enhanced polyploidization and suppressed the polyploidization defect of hepatocytes deficient for atypical E2Fs. In addition, E2F8 and E2F1 were found on the same subset of target promoters. Contrary to the long-standing hypothesis that polyploidization indicates terminal differentiation and senescence, we show that prevention of polyploidization through inactivation of atypical E2Fs has, surprisingly, no impact on liver differentiation, zonation, metabolism and regeneration. Together, these results identify E2F8 as a repressor and E2F1 as an activator of a transcriptional network controlling polyploidization in mammalian cells.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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