The aim was to explore whether the incidence of tonsillar squamous cell carcinomas (TSCCs) increased in Eastern Denmark, 2000–2010, and whether human papillomavirus (HPV) could explain the increase, ...and to assess the association of HPV prevalence with gender, age, and origin (i.e., the certainty of tonsillar tumor origin). We applied HPV DNA PCR and p16 immunohistochemistry to all TSCCs registered in the Danish Head and Neck Cancer Group (DAHANCA) and in the Danish Pathology Data Bank (n = 632). Pathologists reviewed and subdivided the tumors into two groups: specified and nonspecified TSCCs. Approximately 10% of HPV‐positive tumors was genotyped by amplicon next‐generation sequencing. The overall crude incidence of TSCCs increased significantly (2.7% per year) and was explained by an increasing incidence of HPV‐positive TSCCs (4.9% per year). The overall HPV prevalence was 58%, with HPV16 being the predominant HPV type. In multivariate analysis, the HPV prevalence was associated with age (<55 vs. >60 years) (OR, 1.72; 95% CI 1.13–2.63) and origin (nonspecified vs. specified TSCCs) (OR, 0.15; 95% CI 0.11–0.22). The association of HPV prevalence with origin increased over time in specified TSCCs (OR per year, 1.10; 95% CI 1.01–1.19), whereas no change over time was observed among nonspecified TSCCs (OR per year, 0.99; 95% CI 0.90–1.08). In conclusion, the observed increase in the number of HPV‐positive TSCCs can explain the increasing number of TSCCs in Eastern Denmark, 2000–2010. HPV prevalence was associated with younger age (<55 years) and a high certainty of tonsillar tumor origin.
What's new?
Are throat cancers on the rise in Denmark, as in other Western populations? These authors analyzed samples from the Danish Head and Neck Cancer Group, making this the largest non‐selected cohort of tonsillar cancer cases studied to date. They found that during the years 2000–2010, the rate of tonsillar cancer increased, and that HPV could be to blame. The incidence of HPV‐positive cancers rose over the study period, with most of the HPV‐positive cancers harboring HPV‐16. When they classified the tumors by whether they originated in the tonsillar tissue, they found that tumor origin was the strongest predictor of HPV status; specified tonsillar tumors contained HPV more often than those appearing to have originated elsewhere.
Cardiac troponins (cTns) are the cornerstone of diagnosing acute myocardial infarction. There is limited knowledge on the duration of ischemia necessary to induce a measurable release of cTns or the ...very-early-release kinetics of cTns after an ischemic event. Copeptin may have a supplementary role in ruling out myocardial infarction early. We investigated the release of cTns and copeptin in the first hours after experimental balloon-induced ischemia in humans.
Thirty-four patients (median age, 60 years interquartile range, 51-64; 15 men, 43%) with angiographically normal coronary arteries were randomly assigned into 4 groups with different durations of induced myocardial ischemia (0, 30, 60, 90 s). Ischemia was induced by inflating a balloon in the left anterior descending artery between the first and second diagonal branch. Blood was collected before balloon inflation (baseline) every 15 minutes for the first 3 hours, and every 30 minutes for the next 3 hours. The cTns were analyzed by 3 high-sensitivity (hs) cTn assays: hs-cTnT (Roche), hs-cTnI (Siemens), and hs-cTnI (Abbott). Copeptin was analyzed by a sandwich immunoluminometric assay.
None of the patients had any complications. Increased cTn concentrations were detected by all 3 assays, and the magnitude of the increase was associated with the duration of ischemia. Increased hs-cTnI (Siemens) concentrations were first detectable 15 minutes after 90-s ischemia (median 43.7% increase) and increased more steeply and had a higher peak than the other assays. Copeptin levels did not significantly change. Using the cTnT, hs-cTnI (Siemens), and hs-cTnI (Abbott) concentrations at 0 and 180 minutes, 1 (11%), 0, and 0 patients from the 60-s ischemia group and 5 (63%), 2 (25%), and 1 (11%) from the 90-s ischemia group, respectively, fulfilled criteria for a biochemical myocardial infarction.
This study is the first to report the early-release kinetics of cTn concentrations after different durations of experimental coronary balloon occlusion in humans. All assays detected a cTn increase after only 30 s of ischemia. hs-cTnI (Siemens) rose faster and reached a higher peak. Copeptin levels did not change significantly. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03203057.
Summary Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition characterised clinically by skin fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cancer. The condition ...is caused by germline mutations in the FLCN gene, which encodes folliculin; the function of this protein is largely unknown, although FLCN has been linked to the mTOR pathway. The availability of DNA-based diagnosis has allowed insight into the great variation in expression of FLCN , both within and between families. Patients can present with skin signs and also with pneumothorax or renal cancer. Preventive measures are aimed mainly at early diagnosis and treatment of renal cancer. This Review gives an overview of current diagnosis and management of BHD.
The present study describes diagnostic and prognostic abilities of Cerebrospinal fluid (CSF) Pentraxin 3 (PTX3) in central nervous system (CNS) infections. CSF PTX3 was measured retrospectively from ...174 patients admitted under suspicion of CNS infection. Medians, ROC curves and Youdens index was calculated. CSF PTX3 was significantly higher among all CNS infections and undetectable in most of the patients in the control group, and significantly higher in bacterial infections compared to viral and Lyme infections. No association was found between CSF PTX3 and Glasgow Outcome Score. PTX3 in the CSF can distinguish bacterial infection from viral and Lyme infections and non-CNS infections. Highest levels were found in bacterial meningitis. No prognostic abilities were found.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori ...infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.
Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.
In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Hematological patients, receiving intensive chemotherapy (predominantly acute leukemia patients), have repeated postchemotherapy periods with severe bone marrow suppression. As a result, ...these patients require regular monitoring of the complete blood counts (CBC) for optimal patient care. To reduce the strain on the patient, there is a need for a point‐of‐care (POC) hematology device that provides rapid and reliable results both in general and in cytopenic samples and is suitable for outpatient clinics. We evaluated the HemoScreen device for the most used CBC parameter both overall and at the lower range.
Methods
The HemoScreen was compared with the Sysmex XN‐9000 in 206 routine venous samples and 79 capillary bedside samples focusing on white blood cells (WBC), absolute neutrophil count (ANC), red blood cells (RBC), PLT and HGB.
Results
The HemoScreen was less precise compared to the acceptance criteria set for larger and more advanced hematology instrument with a CV% 3.0‐3.7 for WBCs, 3.6‐8.4 for ANCs, 1.1‐1.5 for RBCs, 2.5‐4.4 for PLTs, and 1.7‐2.3 for HGB. Correlation coefficient for all five parameters for the entire range was r >.95 and r >.90 at lower range for venous and capillary samples. Bias limits were within the CTCAE acceptance limits.
Conclusions
The HemoScreen provides rapid and accurate test results, for evaluation of WBC, PLT, and HGB, as well as at low concentrations for guiding transfusions and postchemotherapy treatment. The device is easy to operate and can measure both venous and capillary samples. Therefore, the HemoScreen is well suited for smaller outpatient clinics and potentially home use.
Background Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, ...pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes. Methods In a prospective early pregnancy (PEP) cohort (2016-2017), 203 pregnant women were recruited from 4 to 8 weeks' gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6-8, 8-10, 10-12 and >12 weeks' gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5-97.5th percentiles) and compared with the conventional RIs for non-pregnant women. Results Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks' gestation. Conclusions We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.
Objective
Patients in anticancer treatment with a known side effect of neutropenia are monitored closely with laboratory measurements of white blood cell count (WBC) and differentiation. This study ...sought to evaluate measurement properties and feasibility of patients' self‐testing using a point‐of‐care testing (POCT) device.
Methods
A prospective feasibility and measurement study comparing the standard measurement of cancer patients' WBC and neutrophil count with POCT measurements. The study included 60 outpatients and 22 inpatients from a department of oncology at a university hospital.
Results
Patients successfully conducted 106 measurements using the POCT device. 46% of the patients were >70 years. Weighted Deming regression analysis showed minimal yet significant proportional bias between methods, with POCT increasingly underestimating both total WBC and neutrophils compared with the standard method the higher the count. Over 90% of patients reported they were willing and considered themselves able to use the POCT device at home.
Conclusions
The instrument can be used for self‐testing of post‐anticancer leukopenia and has sufficient measurement precision for patient risk stratification. Patients are able and willing to conduct measurements including when in a situation of acute illness. Further studies are needed to confirm safety and value within patients’ own home.
Concentrations of maternal glucose and lipid during pregnancy affect both fetal growth and the risk of pregnancy complications. The aim of this study was to investigate the effect of two different ...exercise interventions on maternal blood HbA1c and lipid concentrations. Healthy pregnant women (n=219) were enrolled in the study at gestational age ≤15+0 weeks and randomized 2:2:1 to supervised exercise sessions three times per week, to a motivational group having seven counselling sessions on physical activity, or to standard care. Venous blood samples were drawn at 6+4 to 15+0 weeks, at 28+0-6 weeks, at 34+0-6 weeks and at delivery. HbA1c, total cholesterol, LDL-C and triglyceride concentrations were measured by standard biochemical methods and compared within and between groups using constrained linear mixed models. No differences in HbA1c or lipid concentrations between the groups were detected (Figure 1). Overall, HbA1c decreased from ≤15+0 to 28+0-6 weeks (p<0.001) and increased from ≤15+0 to 34+0-6 weeks (p=0.032). Overall, total cholesterol, LDL-C and triglyceride concentrations increased throughout pregnancy (all p<0.001 for ≤15+0 weeks vs. 28+0-6 weeks, 34+0-6 weeks and delivery). Exercise interventions did not affect maternal HbA1c or lipid concentrations during pregnancy. The overall pattern of changes during pregnancy resembled findings from previous studies.
Disclosure
I.K.B.Jensen: None. B.Stallknecht: None. T.D.Clausen: None. E.Løkkegaard: None. C.B.Roland: None. S.P.Knudsen: None. A.D.Jessen: None. S.A.Alomairah: None. O.H.Mortensen: None. L.J.Friis-hansen: None. J.M.Bendix: None. S.Molsted: None.
Background
Colorectal cancer (CRC) screening programs using fecal immunochemical test (FIT) have to choose a cut‐off value to decide which citizens to recall for colonoscopy. The evidence on the ...optimal cut‐off value is sparse and based on studies with a low number of cancer cases.
Methods
This observational study used data from the Danish Colorectal Cancer Screening Database. Sensitivity and specificity were estimated for various cut‐off values based on a large number of cancers. Traditionally optimal cut‐off values are found by weighting sensitivity and specificity equally. As this might result in too many unnecessary colonoscopies we also provide optimal cut‐off values for different weighting of sensitivity and specificity/number of needed colonoscopies to detect one cancer.
Results
Weighting sensitivity and specificity equally gives an optimal cut‐off value of 45 ng Hb/ml. This, however, means making 24 colonoscopies to detect one cancer. Weighting sensitivity lower and for example, aiming at making about 16 colonoscopies to detect one cancer, gives an optimal cut‐off value of 125 ng Hb/ml.
Conclusions
The optimal cut‐off value in an FIT population‐based screening program is 45 ng Hb/ml, when as traditionally sensitivity and specificity are weighted equally. If, however, 24 colonoscopies needed to detect one cancer is too huge a burden on the health care system and the participants, 80, 125, 175, and 350 ng Hb/ml are optimal cut‐off values when only 19/16/14/10 colonoscopies are accepted to find one cancer.
If 24 colonoscopies needed to detect one cancer is acceptable for the health care system and the participants, the optimal cut‐off value in fecal immunochemical test screening is 45 ng Hb/ml. When only 19/16/14/10 colonoscopies are accepted to find one cancer, then, the optimal cut‐off value is 80/125/175/350 ng Hb/ml.
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