Search

Introduction. Increased mortality in patients with low serum concentrations of S-25(OH)D has been described, though no causal relationship has been shown. The aim of this cohort study was to investigate the possible association between S-25(OH)D status and all-cause mortality in 5,147 patients attending a university hospital in Denmark from 2003-2008. Methods. Serum was analyzed for ionized calcium (S-Ca2+), parathyroid hormone (S-PTH) and S-25(OH)D. Kaplan-Meier curves were used to analyze the association between S-25(OH)D quartiles, S-PTH-quartiles and all-cause mortality. Cox regression analyzed associations of age, gender, concentrations of ionized calcium, S-PTH and S-25(OH)D with all-cause mortality. Results. Log rank tests for both S-25(OH)D and S-PTH quartiles showed a significant difference across the quartiles. The Cox regression analysis showed a hazard ratio (HR) for death of 1.02 (95% CI: 1.01; 1.03) for S-PTH per pmol/L increase, 1.07 (95% CI: 1.05; 1.10) for S-25(OH)D per 10 nmol/L decrease and 0.54 (95% CI: 0.24; 1.20) for S-Ca2+ per mmol/L increase. Discussion. This study supports growing evidence, that low serum concentrations of 25(OH)D are associated with an increased all-cause mortality; however the nature of the study prevents the finding of a causal relationship. In the Cox regression analysis S-25(OH)D concentrations in the blood were inversely associated with all-cause mortality. Prospective controlled studies are needed to confirm a causal relationship between low S-25(OH)D concentrations and mortality. [ABSTRACT FROM AUTHOR]

Human studies have shown diurnal rhythms of cholesterol and bile acid synthesis, but a better understanding of the role of the circadian system in cholesterol homeostasis is needed for the development of targeted interventions to improve metabolic health. Therefore, we performed a systematic literature search on the diurnal rhythms of cholesterol synthesis and absorption markers and of bile acid synthesis markers. We also examined the diurnal rhythms of the cholesterol synthesis markers lathosterol and desmosterol, and of the cholesterol absorption markers cholestanol, campesterol, and sitosterol in serum samples from the Bispebjerg study. These samples were collected every three hours over a 24-h period in healthy males (n = 24) who consumed low-fat meals. The systematic search identified sixteen papers that had examined the diurnal rhythms of the cholesterol synthesis markers lathosterol (n = 3), mevalonate (n = 9), squalene (n = 2), or the bile acid synthesis marker 7α-hydroxy-4-cholesten-3-one (C4) (n = 4). Results showed that lathosterol, mevalonate, and squalene had a diurnal rhythm with nocturnal peaks, while C4 had a diurnal rhythm with daytime peaks. Furthermore, cosinor analyses of the serum samples showed a significant diurnal rhythm for lathosterol (cosinor p < 0.001), but not for desmosterol, campesterol, sitosterol, and cholestanol (cosinor p > 0.05). In conclusion, cholesterol synthesis and bile acid synthesis have a diurnal rhythm, though no evidence for a diurnal rhythm of cholesterol absorption was found under highly standardised conditions. More work is needed to further explore the influence of external factors on the diurnal rhythms regulating cholesterol homeostasis. [ABSTRACT FROM AUTHOR]

Introduction: In orthopaedics, anterior cruciate ligament (ACL) reconstructions are among the most common surgical interventions. Two methods are preferably used: autografts from the hamstring tendon (HT) or patella tendon (PT). The purpose of this meta-analysis was to compare these two methods when returning to sports., Methods: Eleven studies were included based on a literature search conducted in PubMed. The primary outcome was return to preinjury sport level in athletes. Post-operative results such as the Lysholm score, the International Knee Documentation Committee (IKDC) subjective score, the Tegner Activity Score and KT-1000 arthrometry and autograft re-rupture rates were analysed as secondary outcomes., Results: The analysis showed no significant difference in return to preinjury sports level at a two-year follow-up between patients operated with hamstring or patella autograft. Considering the secondary outcomes, no significant differences were recorded in Lysholm score, IKDC score or re-rupture rate. The Tegner Activity Scale demonstrated a significantly higher activity level in the PT group than in the HT group (OR 0.79, p = 0.003). At the two-year follow-up, the KT-1000 arthrometer analysis also showed a significant difference in laxity, which was higher for the HT autografts (OR -0.31, p = 0.02)., Conclusion: This study showed no significant differences between hamstring and patella autografts. Even so, the choice of method when operated for ACL rupture remains crucial for the individual and should be a weighted decision made jointly by the patient and the physician., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Introduction: The first case of coronavirus disease 2019 (COVID-19) disease caused by severe acute respiratory syndrome coronavirus-2 occurred in Denmark on 27 February 2020. On 10 March, the first case of COVID-19 pneumonia was admitted to Hvidovre Hospital., Methods: Retrospective case review of individuals 18 years or older who were admitted consecutively to Hvidovre Hospital from 10 March through 23 April 2020., Results: A total of 175 individuals were admitted with COVID-19 pneumonia. The median age was 71 years, 48.6% were male and 71% had at least one co-morbidity. The most commonly presenting symptoms were dyspnoea, dry cough, and fever. The majority of patients had lymphopenia, elevated liver function tests and C-reactive protein. Nearly two in three presented with multilobar infiltration by chest X-ray. Respiratory failure leading to invasive mechanical ventilation developed in 27 patients (15.4%). By 20 April, 23 of 175 (13.1%) patients remained hospitalised, 43 (24.6%) had died and 109 (62.3%) had been discharged., Conclusions: The manifestations of COVID-19 at presentation were similar to those seen in other reports. Our population was older, slightly overrepresented by women and had a high level of co-morbidity. COVID-19 admittance was associated with frequent need of intensive care and mechanical ventilation that was associated with a very high mortality., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Hemoglobin A 1c (HbA 1c ) is a long-term measure for glucose concentration in plasma. Since its introduction as a diabetes monitoring tool, and its more recent application as a diagnostic tool, the number of measurements of HbA 1c have risen dramatically. However, HbA 1c change is slow, so repeating measurements should not be done too often. We use a large, unfiltered dataset from 52,017 patients to determine the possible rate of change in HbA 1c concentration. In our laboratory, the critical difference between HbA 1c measurements is 8.5%. Our data show that a 1-unit HbA 1c rise takes 4 weeks to occur, hence, at a HbA 1c concentration around 50 mmol/mol Hgb, a critically increased HbA 1c concentration cannot be determined until after 16 weeks. Conversely a critically lower HbA1c can manifest itself after 2 weeks, but after 7 weeks the dropping tendency stops. The amount of measurements that can be cancelled because they were taken sooner than 16 weeks is 23 percent.

Introduction: The aim of this study was to compare short-term maternal outcomes in healthy primiparous women with uncomplicated pregnancies who delivered a singleton child at term by planned cesarean or planned vaginal delivery., Material and Methods: Nationwide population-based cohort study of 145 821 low-risk primiparous women with healthy singletons in cephalic position in Denmark, 2008-2016. Data from the Medical Birth Register and the Danish National Patient Registry were linked and compared according to planned mode of delivery. Main outcome measures were major morbidity including maternal death, cardiac arrest, hysterectomy and thromboembolic disease. Minor maternal morbidity includes wound infection, postpartum fever, wound rupture and reoperation, bladder lesions, spinal headache and Ogilvie syndrome. Additionally, anal sphincter injuries were registered., Results: The study included 141 782 planned vaginal deliveries and 4039 planned cesarean deliveries. Severe maternal complications occurred in fewer than 1/4000 in both categories. Women with planned cesarean had a slightly higher risk of wound infections (0.17% vs 0.07%; P = 0.04). There were no significant differences in the remaining minor and major outcomes. Women with planned vaginal delivery had a 4.97% risk of obstetric anal sphincter injuries., Conclusions: For healthy primiparous women, both planned vaginal delivery and planned cesarean delivery are highly safe procedures when the short-term maternal outcome is taken into account. Planned cesarean delivery is associated with a slightly increased risk of wound infection compared with planned vaginal delivery. Women with planned vaginal delivery had a 4.97% risk of obstetric anal sphincter injuries., (© 2019 Nordic Federation of Societies of Obstetrics and Gynecology.)

Like the behaviour and physiology of the organism, biochemical parameters are subjected to diurnal variations through the daily 24-h light and dark cycle. Since blood sampling is carried out at all hours of the day and night, repeated blood testing from a patient throughout the day can be biased by diurnal variations, especially in parameters with high-amplitude 24-h rhythms. Concentration changes in biochemical parameters have thus to be interpreted in view of the 24-h rhythm, as only few recommendations regarding the optimal time of venipunctures and time-specific reference intervals exist.

Early growth response transcription factor 1 (EGR1) is expressed in the suprachiasmatic nucleus (SCN) after light stimulation. We used EGR1-deficient mice to address the role of EGR1 in the clock function and light-induced resetting of the clock. The diurnal rhythms of expression of the clock genes BMAL1 and PER1 in the SCN were evaluated by semi-quantitative in situ hybridization. We found no difference in the expression of PER1 mRNA between wildtype and EGR1-deficient mice; however, the daily rhythm of BMAL1 mRNA was completely abolished in the EGR1-deficient mice. In addition, we evaluated the circadian running wheel activity, telemetric locomotor activity, and core body temperature of the mice. Loss of EGR1 neither altered light-induced phase shifts at subjective night nor affected negative masking. Overall, circadian light entrainment was found in EGR1-deficient mice but they displayed a reduced locomotor activity and an altered temperature regulation compared to wild type mice. When placed in running wheels, a subpopulation of EGR1-deficient mice displayed a more disrupted activity rhythm with no measurable endogenous period length (tau). In conclusion, the present study provides the first evidence that the circadian clock in the SCN is disturbed in mice deficient of EGR1.

The purpose of this study was to evaluate bone-to-implant contact (BIC) in two-dimensional (2D) histology compared to high-resolution three-dimensional (3D) synchrotron radiation micro computed tomography (SR micro-CT). High spatial resolution, excellent signal-to-noise ratio, and contrast establish SR micro-CT as the leading imaging modality for hard X-ray microtomography. Using SR micro-CT at voxel size 5 μm in an experimental goat mandible model, no statistically significant difference was found between the different treatment modalities nor between recipient and reconstructed bone. The histological evaluation showed a statistically significant difference between BIC in reconstructed and recipient bone (p < 0.0001). Further, no statistically significant difference was found between the different treatment modalities which we found was due to large variation and subsequently due to low power. Comparing histology and SR micro-CT evaluation a bias of 5.2% was found in reconstructed area, and 15.3% in recipient bone. We conclude that for evaluation of BIC with histology and SR micro-CT, SR micro-CT cannot be proven more precise than histology for evaluation of BIC, however, with this SR micro-CT method, one histologic bone section is comparable to the 3D evaluation. Further, the two methods complement each other with knowledge on BIC in 2D and 3D., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Abnormal plasma concentrations of potassium in the form of hyper- and hypokalemia are frequent among hospitalized patients and have been linked to poor outcomes. In this study, we examined the prevalence of hypo- and hyperkalemia in patients admitted with a fractured hip as well as the association with 30-day mortality in these patients. A total of 7293 hip fracture patients (aged 60 years or above) with admission plasma potassium measurements were included. Data on comorbidity, medication, and death was retrieved from national registries. The association between plasma potassium and mortality was examined using Cox proportional hazards models adjusted for age, sex, and comorbidities. The prevalence of hypo- and hyperkalemia on admission was 19.8% and 6.6%, respectively. The 30-day mortality rates were increased for patients with hyperkalemia (21.0%, p < 0.0001) compared to normokalemic patients (9.5%), whereas hypokalemia was not significantly associated with mortality. After adjustment for age, sex, and individual comorbidities, hyperkalemia was still associated with increased risk of death 30 days after admission (HR = 1.93 [1.55-2.40], p < 0.0001). After the same adjustments, hypokalemia remained non-associated with increased risk of 30-day mortality (HR = 1.06 [0.87-1.29], p = 0.6). Hyperkalemia, but not hypokalemia, at admission is associated with increased 30-day mortality after a hip fracture.

Purpose: We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar surgical extraction applying osteotomy., Materials and Methods: The Medline, Cochrane Library, and Embase databases were searched for RCTs until August 2015. The primary outcome measure was postoperative inflammatory reactions, with a subgroup analysis of surgical site infection (SSI) and alveolar osteitis. A risk-of-bias assessment of the included trials was done according to the Cochrane guidelines., Results: A total of 53 RCTs were identified; however, only 10 could be included in the present review. A meta-analysis of the 10 trials showed a statistically significant reduction in SSI and alveolar osteitis when antibiotics had been used (odds ratio [OR] = 0.30; 95% confidence interval [CI], 0.19 to 0.47; P ≤ .00001). A subgroup meta-analysis of 6 trials showed that preoperative administration of antibiotics perorally or intravenously significantly reduced the incidence of SSI (OR = 0.19; 95% CI, 0.08 to 0.45; P = .0002). A meta-analysis of 5 trials showed that 2 g of preoperative oral amoxicillin was able to reduce the incidence of SSI and the difference was statistically significant (OR = 0.22; 95% CI, 0.08 to 0.59; P = .002). Seven trials reported on alveolar osteitis, 6 studies on oral use, 2 studies on amoxicillin, 2 on metronidazole, 2 on penicillin V, and 1 on the intravenous use of penicillin. The pooled results showed that preoperative antibiotics significantly reduced the prevalence of alveolar osteitis (OR = 0.35; 95% CI, 0.13 to 0.96; P = .04). The subgroup analysis showed that penicillin V was effective in reducing the incidence of alveolar osteitis (OR = 0.1; 95% CI, 0.03 to 0.30; P ≤ .0001)., Conclusions: A single oral dose of 2 g of amoxicillin before lower third molar osteotomy surgical extraction significantly decreased the incidence of SSI. A single dose of 0.8 g of penicillin V before lower third molar osteotomy surgical extraction significantly decreased the incidence of alveolar osteitis., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Different factors related to winter are known to influence the fracture incidence, but little is known about the effect of road surface temperature. This study examines the association between road surface temperature and the daily number of fractures in an urban area during two winters., Material and Methods: Retrospective data collection was conducted on all patients treated at Bispebjerg Hospital, Denmark, for a humeral, ankle, distal radius or hip fracture during the periods October to April 2009/2010 and 2010/2011. Patients were grouped according to age into the following categories: < 15, 15-30, 30-45, 45-60 and > 60 years. Data on road surface temperature (Tp.) were obtained from The Danish Road Directorate and grouped into the following categories: Days with Tp. > 0 °C, Tp. < 0 °C, Tp. > -5 °C, Tp. < -5 °C and ice alert (IA)., Results: A total of 4,892 patients (4,938 fractures) were treated during the study periods. The daily number of distal radius, humeral and ankle fractures increased significantly with decreasing road surface temperature and the presence of IA. For hip fractures no significant association was found. Decreasing temperature was associated with a significant decrease in the daily number of fractures for patients < 15 years, whereas patients > 30 years experienced a significant increase., Conclusion: Decreasing road temperature results in increased numbers of all fractures except hip fractures. Low temperatures is a risk factor for patients > 30 years and a protective factor for patients < 15 years., Funding: not relevant., Trial Registration: not relevant.

Daily oscillations of clock genes have recently been demonstrated in the ovaries of several species. Clock gene knockout or mutant mice demonstrate a variety of reproductive defects. Accumulating evidence suggests that these rhythms act to synchronise the expression of specific ovarian genes to hypothalamo-pituitary signals and that they are regulated by one or both of the gonadotropins. The aim of this study has been to examine the spatio-temporal expression of the clock genes Per1 and Bmal1 during gonadotropin-independent and gonadotropin-dependent follicle development in the rat ovary. We have examined the ovaries of prepubertal rats, of prepubertal rats stimulated with equine chorionic gonadotropin (eCG)/human chorionic gonadotropin (hCG) and of hypophysectomised adult animals. Using quantitative reverse transcription with the polymerase chain reaction, in situ hybridisation histochemistry and immunohistochemistry, we have demonstrated that the expression of the two clock genes is low and arrhythmic in ovarian cells during early gonadotropin-independent follicle development in prepubertal animals and in hypophysectomised animals. We have also demonstrated that the expression of the clock genes becomes rhythmic following eCG stimulation in the theca interna cells and the secondary interstitial cells and that, following additional hCG stimulation, the expression of the clock genes also becomes rhythmic in the granulosa cells of preovulatory follicles. These findings link the initiation of clock gene rhythms in the rat ovary to the luteinising hormone receptor and suggest a functional link to androgen and progesterone production. In hypophysectomised animals, rhythmic clock gene expression is also observed in the corpora lutea and in secondary interstitial cells demonstrating that, in these compartments, entrainment of clock gene rhythms is gonadotropin-independent.

Objective: The aim of this study was to assess the evidence for the association between different biochemical markers at admission and mortality through a meta-analysis., Data Sources: PubMed-, Embase-, Cochran Library and the Web of Knowledge were searched for cohort studies., Study Selection: Eligible studies were observational studies with a study population larger than 150 subjects, a mean age above 60 years and a study duration below 730 days., Data Extraction: Characteristics of studies and outcomes of all-cause mortality were extracted from the retrieved articles. Data were pooled across studies for the individual biomarker using random- or fixed-effect analysis., Data Synthesis: 15 eligible studies of 5 different markers on mortality were studied. The following markers were found to be of prognostic value on mortality in hip fracture patients: low haemoglobin (odds ratio, 2.78; 95% confidence interval, 2.17-3.55; P<0.00001, 3148 subjects included), low total lymphocyte count, TLC (odds ratio, 2.60; 95% confidence interval, 1.61-4.20; P<0.00001, 1689 subjects included), low albumin (odds ratio, 1.83; 95% confidence interval, 1.31-2.56; P=0.0004, 1680 subjects included), low albumin/low TLC (odds ratio, 3.00; 95% confidence interval, 1.81-4.99; P<0.0001, 704 subjects included), low albumin/high TLC (odds ratio, 3.39; 95% confidence interval, 1.83-6.29; P=0.0001, 704 subjects included), high creatinine (odds ratio, 1.58; 95% confidence interval, 1.25-1.99; P=0.0001, 3761 subjects included), and high PTH (odds ratio, 15.43; 95% confidence interval, 3.60-66.14; P=0.0002, 525 subjects included)., Conclusion: Biochemical markers at admission are valid predictors of mortality in hip fracture patients., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: The objective of the study was to identify possible prognostic factors in patients with salicylic poisoning., Material and Methods: A chart review on 53 patients with salicylic poisoning was performed. Clinical and biochemical data were registered for all patients with a serum level of salicylic acid higher than or equal to 2 mmol/l in the 2004-2008 period. The patients were divided into groups according to the outcome of the poisoning. A complicated outcome was defined as: hospital stay > 48 hours, dialysis, persisting complications at discharge or death., Results: In the group with complicated outcome, chronic poisoning (43% versus 13%, p = 0.02) and medical diseases (24% versus 9%, p = 0.07) were more prevalent and the proportion of elderly (55 years versus 38 years, p = 0.003) and alcoholics (48% vs. 25%, p = 0.09) were higher. The mortality was low, with only one fatality among the acutely poisoned and none among the chronically poisoned. Neurological symptoms (somnolence and confusion) were the only symptoms which differed significantly between the two groups (67% versus 28%, p = 0.006), as well as being the only variable independently emerging as a risk factor in the multivariate logistic regression analysis with an odds ratio of 6.6 (95% confidence interval: 1.5-28.9) for a complicated outcome. A significantly lower level of bicarbonate was seen in the group with complicated outcome. Among the other biochemical data, only haemoglobin and certain liver enzymes differed between the two groups, probably due to pre-existing differences., Conclusion: Mortality after salicylic poisoning is low. Chronic poisonings, old age or concurrent medical diseases are associated with a complicated outcome. If neurological symptoms or low standard-HCO3- are present, the prognosis is poor.

Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) have important local functions within the myocardium, where they protect against accelerated fibrosis. As circadian expression of cardiac natriuretic peptides could be of importance in local cardiac protection against disease, we examined the diurnal changes of the mRNAs encoding ANP, BNP, and their common receptor NPR-A in atrial and ventricular myocardium. Forty eight mice were killed at the following ZT times: 4, 8, 12, 16, 20, and 24, where ZT designates Zeitgeber; ZT 0 corresponds to lights ON and ZT 12 corresponds to lights OFF. Eight animals (4 males and 4 females) were included at each time point. Another 48 animals were killed during the second cycle of dark/dark (designated Circadian Time or CT: CT 4, CT 8, CT 12, CT 16, CT 20, and CT 24). The cellular contents of the clock genes Per1 and Bmal1 as well as ANP, BNP, and their common receptor (NPR-A) were determined using RT-PCR. Per1 and Bmal1 mRNA contents oscillated in antiphase in both atrial and ventricular regions, where Bmal1 mRNA peaked 12h out of phase relative to Per1 mRNA. ANP and NPR-A atrial mRNA contents revealed borderline significant diurnal changes, whereas ventricular BNP mRNA contents exhibited pronounced oscillation during constant darkness with nadir at CT 12 (P<0.0001). In conclusion, we report a chamber-dependent circadian profile of cardiac BNP mRNA contents, which is not paralleled by the related ANP gene. Our findings suggest that the BNP mRNA pattern could be associated with increased cardiac susceptibility and response to disease., (Copyright 2009 Elsevier B.V. All rights reserved.)

Background: Quantitative bibliometric measurements of research activity are frequently used, e.g. for evaluating applicants for academic positions. The purpose of this investigation is to assess research activity within the medical speciality of Clinical Biochemistry by comparing it with a matched control group from other medical specialities in Denmark., Materials and Methods: A list of all physicians registered in Denmark (23,127 persons) was drawn from the database "Laeger.dk". Of these, 5,202 were generalists (not included) while 11,691 were from other specialities. Of the 126 specialists from Clinical Biochemistry, 57 fulfilled the inclusion criteria. Each of these 57 was matched according to medical title with two randomly chosen specialists from other specialities, totaling 114. Using Medline and the Web of Science, the number of publications and the number of citations were then ascertained., Results: 25% of the 11,691 specialists held a PhD degree or doctoral degree, DMSci, (Clinical Biochemistry: 61%). The 171 specialists included in the study had 9,823 papers in Medline and 10,140 papers in the Web of Science. The number of Medline papers per specialist was 71 for Clinical Biochemistry compared to 51 for the control group. The number of citations per specialist was 1,844 for Clinical Biochemistry compared to 816 for the control group. The top ten H-indices (of which 8 were in Clinical Biochemistry) ranged from 30 to 69., Conclusion: Both the number of papers and the number of citations were higher for Clinical Biochemistry than for the control group. The difference was most pronounced among professors.

Reduced physical activity or immobilisation have several negative effects on the skeleton. Significant reductions in bone mass have been observed after prolonged bed rest, in patients with injury to the spinal cord and hemiplegia, and after transitory immobilisation of the extremities, for instance after fractures. The aim of this literature review was to evaluate the effect of exercise on bone mass in elderly people and to determine whether exercise programmes could be appropriate in the prevention of fractures in this segment of the population. We identified four randomised and two non-randomised, prospective studies for the analysis of the effect of exercise on bone mass. Four studies reported a statistically significant difference in the intervention group, as compared to the control group, whereas two studies failed to find any significant differences in bone mass. We conclude that exercise has a beneficial and measurable effect on bone mass in the elderly, which may lead to a decline in the rate of fractures.