By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.
Current clinical problems in colorectal cancer (CRC) diagnostics and therapeutics include the disease complexity, tumor heterogeneity, and resistance to targeted therapeutics. In the present study, we examined 171 CRC adenocarcinomas from Greek patients undergoing surgery for CRC to determine the frequency of KRAS, BRAF, and PIK3CA point mutations from different areas of tumors in heterogeneous specimens. Ninety two out of 171 (53.8%) patients were found to bear a KRAS mutation in codons 12/13. Of the 126 mutations found, 57.9% (73/126) were c.38G>A mutations (p.G13D) and 22.2% (28/126) were c.35G>T (p.G12V). Remarkably, RAS mutations in both codons 12 and 13 were recorded in the same tumor by pyrosequencing. Moreover, differences in KRAS mutations between tumor center and periphery revealed tumor heterogeneity in 50.7% of the specimens. BRAF c.1799T>A (V600E) mutations were moderately detected in 4/171 (2.3%) specimens, whereas most PIK3CA mutations were revealed by pyrosequencing 6/171 (3.5%). Remarkable tumor heterogeneity is revealed, where double mutations of KRAS in the same tumor and different KRAS mutation status between tumor core and margin are detected with high frequency. It is expected that these findings will have a major impact in cancer diagnosis and personalized therapies.
SummaryObjectiveThere is limited knowledge about the natural history of normocalcaemic, vitamin D‐sufficient hyperparathyroidism (nHPT). The aim was to study the prevalence of nHPT and its relation to morbidity.DesignCross‐sectional and retrospective study at the Sahlgrenska University Hospital, Gothenburg, Sweden.SubjectsA random population of 608 men and women, age 25–64 years, was studied in 1995 as part of the WHO MONICA study and reinvestigated in 2008 (n = 410, of whom 277 were vitamin D sufficient).MeasurementsA serum intact parathyroid hormone (S‐PTH) ≥60 ng/l was considered as HPT, S‐calcium 2·15–2·49 mmol/l as normocalcaemia and S‐25(OH)D ≥ 50 nmol/l as vitamin D sufficiency. Data on fractures, stroke and myocardial infarction were retrieved until 2013, that is a 17‐year follow‐up.ResultsThe prevalence of nHPT was 2·0% in 1995 (age 25–64) and 11·0% in 2008 (age 38–79). S‐PTH was positively correlated with age and BMI. After adjustment for these variables, a high S‐PTH level (≥60 ng/l) at follow‐up was associated with previously low S‐25(OH)D, high osteocalcin, S‐PTH and both past and presently treated hypertension. No relation was seen with creatinine, cystatin C, malabsorption markers, thyroid function, glucose, insulin, lipids, calcaneal quantitative ultrasound, fractures, myocardial infarction, stroke or death at follow‐up.ConclusionsThis small random population study showed that nHPT was common, 11% at follow‐up. Only one individual developed mild hypercalcaemia in 13 years. Previous S‐PTH was predictive of nHPT and hypertension was prevalent, but no increase in hard end‐points was seen over a 17‐year period.
Compared to previous studies, we noticed a low incidence of "true" incidental prostatic carcinoma but a high ratio of poorly differentiated tumors (all stage T1b). Compared to the group as a whole, patients with incidental prostate cancer were older and had smaller prostate and transition zone volumes. Further research is needed to identify parameters that may aid in the earlier identification of incidental prostate cancer, as patients may benefit from curative treatment.
Hyperparathyroidism (HPT), including normocalcaemic, vitamin D sufficient (Serum (S)-25(OH)D ! 50 nmol/L) hyperparathyroidism (nHPT), has increasingly been diagnosed in the last few decades due to the more common use of the serum parathyroid hormone (S-PTH) assay. We investigated if men with HPT had higher morbidity and mortality than men without HPT during 21 years' follow-up. A random population sample of 750 men, all 50 years of age, was examined in 1993. Endpoints were retrieved 21 years later at 71 years of age. Albumin-corrected serum (S) calcium, S-25-hydroxyvitamin D and S-PTH were assessed along with data on cardiovascular risk factors and medication. Outcome data on fractures, stroke, myocardial infarction, cancer and death were retrieved in 2014; 21 years after primary assessment. The prevalence of HPT at 50 years of age was 9.3%; nHPT 2.8%, primary HPT 0.4%, secondary HPT 0.4%, and HPT with vitamin D insufficiency 6%. Fracture rate, myocardial infarction, stroke, cancer and death occurred similarly in men with or without HPT, as well as in men with nHPT as compared with men without calcium/PTH aberrations during 21 years' follow-up. S-PTH was evenly distributed in the univariable analyses for each outcome. Cox regression analyses showed no increase in serious morbidity or in mortality in men with HPT, irrespective of cause, compared with men with normal S-PTH over a 21-year period. None had HPT at a S-25(OH)D level of 100 nmol/L.
This work marks a thorough analysis of a confidential real‐time dataset consisting of the Eurosystem/ECB staff macroeconomic projections since their existence. By applying techniques widely employed in the literature of forecast evaluation, we examine their statistical properties with a special emphasis on optimality and rationality. Long‐term GDP projections are biased (tendency to overpredict), do not fully account for available information, and are outperformed by private sector expectations. Inflation projections are optimal and rational on a full‐sample analysis; however, subsample analysis reveals two distinct periods with a persistent and significant bias. Before the financial crisis inflation was persistently underpredicted, while in post‐2013, the bias reverses into overprediction.
Objective: Hypoparathyroidism (HypoPT) is a rare endocrine disorder in which insufficient levels of parathyroid hormone (PTH) lead to low serum calcium levels and muscular cramps. The aim was to study the Health-Related Quality of Life (HRQoL) and comorbidities in patients with HypoPT compared with the general population and estimate the need of treatment with PTH-analogue. Design: Patients with HypoPT were identified and compared with a population sample. Short Form-36 (SF-36) and EuroQol-5 Dimensions Visual Analogue Scale (EQ5D-VAS) questionnaires were used. All patients were followed-up at the Sahlgrenska University Hospital outpatient clinic. Methods: From the medical records between 2007 and 2020, 203 patients with HypoPT were identified and compared with a population sample (n=414), from the WHO MONICA project, Gothenburg, Sweden. Of the 203 patients who met the diagnostic criteria, 164 were alive and 65% answered the HRQoL questionnaires. Results: Patients with HypoPT, 80% postsurgical, and controls had similar age (60 years) and sex distribution (80% women). Patients had lower SF-36 summary component scores for physical [40.0(IQR:21) versus 51.2(IQR:14.6); p<0.001] and mental [43.1(IQR:17.4) versus 56.1(IQR:13.3); p<0.001] well-being, irrespective of etiology or calcium levels. Individuals with HypoPT had more medications and lower renal function, but not higher mortality, than controls. Low HRQoL together with low calcium were present in 23% of individuals with HypoPT. Conclusion: HRQoL was markedly lower in patients with HypoPT than in controls and independent of serum calcium levels. Treatment with PTH-analogue could be considered at least among patients with both low HRQoL and low calcium levels.
Background Teriparatide was the first anabolic agent recommended for the treatment of osteoporosis. Long-term real-world, controlled studies are not available. The purpose was to evaluate the long-term effects of treatment with teriparatide on fractures and Health Related Quality of Life in subjects with established osteoporosis in comparison with placebo treated patients with osteoporosis and the general population. Methods A 10-year follow-up was performed after a prospective, open-labelled study with teriparatide 20 μg given subcutaneously daily for a mean of 18 months (range 14–24 months) in 40 women, mean age 69 years, with osteoporosis and vertebral compression. Placebo treated women, n = 25, mean age 60 years, from a randomized, double-blind, placebo-controlled growth hormone trial with daily subcutaneous injections for 18 months, with osteoporosis were used as controls. Dual energy x-ray absorptiometry and questionnaires were performed at start, after 18 months, after 36 months and after 10 years. Women, n = 233, of similar age from a random population sample, also served as controls and were followed in parallel. All fractures were X-ray verified. Results Fractures decreased from 100 to 35% in the teriparatide treated patients (p < 0.0001) to similar levels as in the population sample, 25 to 28% at start and after 10 years, respectively. Bone mineral density increased on teriparatide but returned to levels at treatment start after 10 years. Health Related Quality of Life was lower in the teriparatide group than in the population (p < 0.001) before and, after treatment and at 10 years. Conclusions Anabolic hormonal treatment with teriparatide reduced fracture prevalence to similar levels as in the general population at 10 years’ follow-up. Health Related Quality of Life was low in osteoporosis and unaffected by bone specific treatment.
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