A Retrospective Study of 291 Patients With Head and Neck Sarcomas: Treatment, Outcomes, and Prognostic Factors.

AIMS: Sarcomas constitute a group of rare malignant neoplasms, commonly subcategorized into soft tissue sarcomas (STS) and bone sarcomas. This study aims to describe the treatment modalities and outcome of head and neck sarcoma (HNS) patients in western Denmark and to identify prognostic factors for overall survival and recurrence in HNS patients. MATERIALS AND METHODS: The Aarhus sarcoma registry, The National Danish Sarcoma Database, and the Danish National Pathology Registry were used to identify HNS adult patients diagnosed between 1979 and 2022. RESULTS: Altogether, 291 patients were included in this study. The prevalent histological subtypes were undifferentiated pleomorphic sarcoma (16%; 48/291) and leiomyosarcoma (15%; 44/291) for STS patients (n = 230) and chondrosarcoma (10%; 28/291) and osteosarcoma (7%; 19/291) for bone sarcoma patients (n = 61). Surgery with curative intent was performed in 71% (164/230) and 70% (43/61) of STS and bone sarcoma patients, respectively. Clear resection was achieved in 59% (97/164) of STS patients and 44% (19/43) of bone sarcoma patients. Eighty-nine patients relapsed (STS n = 66, bone sarcoma n = 23) after a median time of 2.7/5.5 years for STS/bone sarcoma patients. The five-year overall survival rates were 45% for STS patients and 66% for bone sarcoma patients. The following factors were significantly, negatively associated with overall survival in STS patients: Age (hazard ratio (HR)) = 1.02, p < 0.001), tumour size ≥5 cm (HR = 1.75, p = 0.003), metastatic disease (HR = 3.17, p < 0.001), high grade tumour (HR = 2.24, p = 0.004), previous cancer (HR = 2.84, p < 0.001), and high Aarhus composite biomarker score (ACBS) (HR = 4.56, p = 0.001). For relapse in STS patients, higher tumour grade (HR = 3.19, p = 0.014), intralesional margins (HR = 2.84, p < 0.001), ≥2 previous cancers (HR = 3.00, p = 0.004), and high ACBS (HR = 3.29, p = 0.047), were negatively associated. For bone sarcomas only higher age (HR = 1.02, p = 0.049) and intralesional margins (HR = 2.91, p = 0.042) were significant negative factors for overall survival. CONCLUSION: Multiple prognostic factors for overall survival and relapse were identified, especially for STS patients.

Four-Way Wada: SEEG-based mapping with electrical stimulation, high frequency activity, and phase amplitude coupling to complement traditional Wada and functional MRI prior to epilepsy surgery.

Presurgical evaluation of refractory epilepsy involves functional investigations to minimize postoperative deficit. Assessing language and memory is conventionally undertaken using Wada and fMRI, and occasionally supplemented by data from invasive intracranial electroencephalography, such as electrical stimulation, corticortical evoked potentials, mapping of high frequency activity and phase amplitude coupling. We describe the comparative and complementary role of these methods to inform surgical decision-making and functional prognostication. We used Wada paradigm to standardize testing across all modalities. Postoperative neuropsychological testing confirmed deficit predicted based on these methods.

Pre-eclampsia screening in Denmark (PRESIDE): national validation study.

OBJECTIVES: To investigate the predictive performance of the Fetal Medicine Foundation (FMF) first-trimester screening algorithm for pre-eclampsia in a Danish population and compare screening performance with that of the current Danish strategy, which is based on maternal risk factors. METHODS: This was a prospective study of women with a singleton pregnancy attending for their first-trimester ultrasound scan and screening for aneuploidies at six Danish university hospitals between May 2019 and December 2020. Prenatal data on maternal characteristics and medical history were recorded, and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum pregnancy-associated plasma protein-A (PAPP-A) and serum placental growth factor (PlGF) were collected without performing a risk assessment for pre-eclampsia. Information on acetylsalicylic acid use was recorded. After delivery, pregnancy outcome, including gestational age at delivery and pre-eclampsia diagnosis, was recorded. Pre-eclampsia risk assessment for each woman was calculated blinded to outcome using the FMF screening algorithm following adjustment to the Danish population. Detection rates (DRs) of the FMF algorithm were calculated for a fixed screen-positive rate (SPR) of 10% and for the SPR achieved in the current Danish screening. RESULTS: A total of 8783 pregnant women were included, with a median age of 30.8 (interquartile range (IQR), 28.1-33.9) years. The majority were white (95%), naturally conceiving (90%), non-smokers (97%) and had no family history of pre-eclampsia (96%). The median body mass index was 23.4 (IQR, 21.2-26.6) kg/m2 . A complete risk assessment including maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A was available for 8156 women (92.9%). In these women, UtA-PI was measured bilaterally with a median value of 1.58 (IQR, 1.27-1.94) and the median resting MAP of 80.5 (IQR, 76.1-85.4) mmHg in two consecutive measurements. Among these, 303 (3.7%) developed pre-eclampsia, including 55 (0.7%) cases of pre-eclampsia with delivery < 37 weeks of gestation and 16 (0.2%) cases of pre-eclampsia with delivery < 34 weeks. At a SPR of 10%, combined screening using the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A had a DR of 77.4% (95% CI, 57.6-97.2%) for pre-eclampsia with delivery < 34 weeks, 66.8% (95% CI, 54.4-79.1%) for pre-eclampsia with delivery < 37 weeks and 44.1% (95% CI, 38.5-49.7%) for pre-eclampsia with delivery at any gestational age. The current Danish screening strategy using maternal risk factors detected 25.0% of women with pre-eclampsia with delivery < 34 weeks and 19.6% of women with pre-eclampsia with delivery < 37 weeks at a SPR of 3.4%. When applying the FMF algorithm including maternal characteristics, MAP, UtA-PI and PlGF at the fixed SPR of 3.4%, the DRs were 60.5% (95% CI, 36.9-84.1%) for PE with delivery < 34 weeks and 45.2% (95% CI, 32.0-58.5%) for PE with delivery < 37 weeks. CONCLUSION: In this large Danish multicenter study, the FMF algorithm based on maternal characteristics, MAP, UtA-PI, PlGF and PAPP-A predicted 77.4% of cases with pre-eclampsia with delivery < 34 weeks and 66.8% of cases with pre-eclampsia with delivery < 37 weeks of gestation at a SPR of 10%, suggesting that the performance of the algorithm in a Danish cohort matches that in other populations. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Scandcleft randomized trials of primary surgery for unilateral cleft lip and palate: Speech proficiency at 10 years of age.

BACKGROUND & AIM: To assess consonant proficiency and velopharyngeal function in 10-year-old children born with unilateral cleft lip and palate (UCLP) within the Scandcleft project. METHODS & PROCEDURES: Three parallel group, randomized, clinical trials were undertaken as an international multicentre study by nine cleft teams in five countries. Three different surgical protocols for primary palate repair (Arm B-Lip and soft palate closure at 3-4 months, hard palate closure at 36 months, Arm C-Lip closure at 3-4 months, hard and soft palate closure at 12 months, and Arm D-Lip closure at 3-4 months combined with a single-layer closure of the hard palate using a vomer flap, soft palate closure at 12 months) were tested against a common procedure (Arm A-Lip and soft palate closure at 3-4 months followed by hard palate closure at 12 months) in the total cohort of 431 children born with a non-syndromic UCLP. Speech audio and video recordings of 399 children were available and perceptually analysed. Percentage of consonants correct (PCC) from a naming test, an overall rating of velopharyngeal competence (VPC) (VPC-Rate), and a composite measure (VPC-Sum) were reported. OUTCOMES & RESULTS: The mean levels of consonant proficiency (PCC score) in the trial arms were 86-92% and between 58% and 83% of the children had VPC (VPC-Sum). Only 50-73% of the participants had a consonant proficiency level with their peers. Girls performed better throughout. Long delay of the hard palate repair (Arm B) indicated lower PCC and simultaneous hard and soft palate closure higher (Arm C). However, the proportion of participants with primary VPC (not including velopharyngeal surgeries) was highest in Arm B (68%) and lowest in Arm C (47%). CONCLUSIONS & IMPLICATIONS: The speech outcome in terms of PCC and VPC was low across the trials. The different protocols had their pros and cons and there is no obvious evidence to recommend any of the protocols as superior. Aspects other than primary surgical method, such as time after velopharyngeal surgery, surgical experience, hearing level, language difficulties and speech therapy, need to be thoroughly reviewed for a better understanding of what has affected speech outcome at 10 years. WHAT THIS PAPER ADDS: What is already known on the subject Speech outcomes at 10 years of age in children treated for UCLP are sparse and contradictory. Previous studies have examined speech outcomes and the relationship with surgical intervention in 5-year-olds. What this study adds to the existing knowledge Speech outcomes based on standardized assessment in a large group of 10-year-old children born with UCLP and surgically treated according to different protocols are presented. While speech therapy had been provided, a large proportion of the children across treatment protocols still needed further speech therapy. What are the potential or actual clinical implications of this work? Aspects other than surgery and speech function might add to the understanding of what affects speech outcome. Effective speech therapy should be available for children in addition to primary surgical repair of the cleft and secondary surgeries if needed.

Scoring sleep using respiration and movement-based features.

Rules derived from standard Rechtschaffen and Kales criteria were developed to accurately score rodent sleep into wake, rapid eye movement (REM) sleep, and non-REM sleep using movements detected by non-contact electric field (EF) sensors. • Using this method, rodent sleep can be scored using only respiratory and gross body movements as a validated, non-invasive alternative to electrode techniques. • The methodology and rules established for EF sensor-based sleep scoring were easily learned and implemented. • Examples of expert-scored files are included here to help novice scorers self-train to score sleep. Though validated in mice, sleep scoring using respiratory movements has the potential for application in other species and through other movement-based technologies beyond EF sensors.

Severity and 1-month outcome of SARS-CoV-2 infection in patients with solid cancers: a Danish nationwide cohort study.

BACKGROUND: Cancer patients are vulnerable to infections, are older and often have comorbidities in comparison to the general population, which increases the risk for severe outcomes related to COVID-19 diagnosis. METHODS: This study is a prospective, nationwide study in patients with solid cancer and SARS-CoV-2 infection included between 10 March to 15 June 2020. Patient's baseline characteristics were collected. The study's primary outcome was overall survival within 30 days of verified SARS-CoV-2 infection. Secondary outcomes were hospital admission, admission to an ICU, and need for supplemental oxygen. RESULTS: A total of 112 patients with a cancer diagnosis and verified SARS-CoV-2 infection were identified. After one month of follow up, hospitalization was required for 54% (n = 61) and 21% of the patients had died and 14 of the 23 deceased cancer patients were ≥70 years. Most patients were classified with mild COVID-19 symptoms (66%, n = 74); however, 48% (n = 23) of the ≥70-year-olds patients were classified with severe or critical COVID-19 symptoms. Among the total study population, 61% (n = 68) had comorbidities and comorbidity were more frequently observed among the deceased (91%, n = 21) and older cancer patients (≥70 years, 81%, n = 39). CONCLUSIONS: Acknowledging the low sample size in this study, our work shows that age and comorbidities, but not recent cytotoxic therapy, are associated with adverse outcomes of SARS-CoV-2 infection for patients with solid cancer. Particularly, patients with progressive disease seem to be at greater risk of a fatal outcome from COVID-19.HighlightsAge, performance status, and comorbidities are strong predictors of adverse outcome in cancer patients with SARS-CoV-2 infection.Patients with progressive cancer disease seem to be at greater risk of a fatal outcome from COVID-19.Recent cytotoxic therapy, however, did not seem to be associated with increased risk for adverse outcomes of SARS-CoV-2 infection for patients with solid cancer.

Radiation-Induced Sarcoma: A Retrospective Population-Based Study Over 34 Years in a Single Institution.

AIMS: About a half of all cancer patients receive radiotherapy as part of their oncological treatment. Because of the carcinogenic effect of ionising radiation, there is a rare, but definite, risk of developing secondary malignancies, including sarcomas. The aim of this retrospective study was to describe the prevalence, patient and tumour characteristics, as well as prognosis and outcome, of patients with radiation-induced sarcomas (RIS) in a cohort of patients treated in the Sarcoma Centre at Aarhus University Hospital over a period of 34 years. MATERIALS AND METHODS: All patients who fulfilled the criteria for RIS and were treated for RIS in the period 1979-2013 were included. Patient data were retrieved from the Aarhus Sarcoma Registry and the National Danish Sarcoma Database, crosschecked with the National Register of Pathology and validated using the patients' medical records. The primary end point was the effect of surgery and treatment intent on overall survival. Overall survival is reported using the Kaplan-Meier estimates and compared using the Log-rank test. Descriptive statistics are presented for patients, tumours and treatment characteristics. RESULTS: Of 2845 patients diagnosed with sarcoma between 1979 and 2013, 64 (2%) were diagnosed with RIS. The median interval from the original malignancy was 11 years. The most common histological type was undifferentiated pleomorphic sarcoma (33%). Curative treatment was intended for 45 patients. Fifty patients underwent surgery, of whom 80% had microscopically radical resection (R0). The 5-year overall survival for the whole cohort was 32%. Patients who underwent surgery had a significantly better overall survival compared with patients who were not treated with surgery. In the univariate Cox proportional hazard analyses, no metastases at diagnosis, surgery and R0 resection were favourable prognostics factors of survival. CONCLUSION: This study showed that RIS patients are unique in their epidemiology and tumour characteristics. They have a poor prognosis and need special research investigating new intensive treatment strategies to improve the outcome.

Management of Pregnant Inflammatory Bowel Disease Patients During the COVID-19 Pandemic.

The rapid emergence of the novel coronavirus [SARS-CoV2] and the coronavirus disease 2019 [COVID-19] has caused significant global morbidity and mortality. This is particularly concerning for vulnerable groups such as pregnant women with inflammatory bowel disease [IBD]. Care for pregnant IBD patients in itself is a complex issue because of the delicate balance between controlling maternal IBD as well as promoting the health of the unborn child. This often requires continued immunosuppressive maintenance medication or the introduction of new IBD medication during pregnancy. The current global COVID-19 pandemic creates an additional challenge in the management of pregnant IBD patients. In this paper we aimed to answer relevant questions that can be encountered in daily clinical practice when caring for pregnant women with IBD during the current COVID-19 pandemic. PODCAST: This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast.

Noninvasive three-state sleep-wake staging in mice using electric field sensors.

STUDY OBJECTIVE: Validate a novel method for sleep-wake staging in mice using noninvasive electric field (EF) sensors. METHODS: Mice were implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes and housed individually. Noninvasive EF sensors were attached to the exterior of each chamber to record respiration and other movement simultaneously with EEG, EMG, and video. A sleep-wake scoring method based on EF sensor data was developed with reference to EEG/EMG and then validated by three expert scorers. Additionally, novice scorers without sleep-wake scoring experience were self-trained to score sleep using only the EF sensor data, and results were compared to those from expert scorers. Lastly, ability to capture three-state sleep-wake staging with EF sensors attached to traditional mouse home-cages was tested. RESULTS: EF sensors quantified wake, rapid eye movement (REM) sleep, and non-REM sleep with high agreement (>93%) and comparable inter- and intra-scorer error as EEG/EMG. Novice scorers successfully learned sleep-wake scoring using only EF sensor data and scoring criteria, and achieved high agreement with expert scorers (>91%). When applied to traditional home-cages, EF sensors enabled classification of three-state (wake, NREM and REM) sleep-wake independent of EEG/EMG. CONCLUSIONS: EF sensors score three-state sleep-wake architecture with high agreement to conventional EEG/EMG sleep-wake scoring 1) without invasive surgery, 2) from outside the home-cage, and 3) and without requiring specialized training or equipment. EF sensors provide an alternative method to assess rodent sleep for animal models and research laboratories in which EEG/EMG is not possible or where noninvasive approaches are preferred.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

BACKGROUND AND PURPOSE: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥35 years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. RESULTS: Amongst the study population (N = 4 670 423), 34 868 (0.75%) had a history of CDI. A total of 165 and 47 035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2 years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. CONCLUSIONS: Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Joint impact of common risk factors on incident dementia: A cohort study of the Swedish Twin Registry.

BACKGROUND: As common risk factors of dementia, nine factors (low education, hearing loss, obesity, hypertension, smoking, depression, physical inactivity, diabetes and social isolation) were proposed. However, the joint impact of these factors on incident dementia is still uncertain; hence, we aimed to examine this impact. METHODS: We conducted a cohort study of 9017 cognitively intact individuals aged ≥ 65 years in the Swedish Twin Registry. The main exposure was the total number of reported risk factors (ranging from 0 to 9). Data on dementia diagnoses were based on clinical workup and national health registers. After estimating the adjusted hazard ratios of incident dementia, the population attributable fraction (PAF) was calculated. We then conducted additional analyses, including APOE ε4 status in a genotyped subsample (n = 2810) to check the relative impact of the main exposure and discordant twin pair (n = 1158) analysis to consider confounding by familial effects (shared genetic or familial environmental factors). RESULTS: The number of dementia cases was 1950 (21.6%). A dose-response relationship between the number of risk factors and incident dementia was observed; hazard ratio (95% confidence interval) per one-unit increment in number of risk factors was 1.07 (1.03 to 1.11). The PAF for the combination of the nine risk factors was 10.4%. The PAF of all nine risk factors was smaller than that of APOE ε4 genotype (20.8%) in the subsample. Discordant pair analysis suggested that the observed association was not likely explained by familial effects. CONCLUSION: The nine risk factors may have considerable impact as modifiable factors on incident dementia.

Clinical osteoarthritis of the hip and knee and fall risk: The role of low physical functioning and pain medication.

OBJECTIVE: Several studies have found an increased fall risk in persons with osteoarthritis (OA). However, most prospective studies did not use a clinical definition of OA. In addition, it is not clear which factors explain this risk. Our objectives were: (1) to confirm the prospective association between clinical OA of the hip and knee and falls; (2) to examine the modifying effect of sex; and (3) to examine whether low physical performance, low physical activity and use of pain medication are mediating these relationships. METHODS: Baseline and 1-year follow-up data from the European Project on OSteoArthritis (EPOSA) were used involving pre-harmonized data from five European population-based cohort studies (ages 65-85, n = 2535). Clinical OA was defined according to American College of Rheumatology (ACR) criteria. Falls were assessed using self-report. RESULTS: Over the follow-up period, 27.7% of the participants fell once or more (defined as faller), and 9.8% fell twice or more (recurrent faller). After adjustment for confounding, clinical knee OA was associated with the risk of becoming a recurrent faller (relative risk=1.55; 95% confidence interval: 1.10-2.18), but not with the risk of becoming a faller. No associations between clinical hip OA and (recurrent) falls were observed after adjustment for confounding. Use of opioids and analgesics mediated the associations between clinical OA and (recurrent) falls, while physical performance and physical activity did not. CONCLUSION: Individuals with clinical knee OA were at increased risk for recurrent falls. This relationship was mediated by pain medication, particularly opioids. The fall risk needs to be considered when discussing the risk benefit ratio of prescribing these medications.

Myocardial injury and mortality in patients with excessive oxygen administration before cardiac arrest.

INTRODUCTION: Hyperoxia after cardiac arrest may be associated with higher mortality, and trials have found that excess oxygen administration in patients with myocardial infarction is associated with increased infarct size. The effect of hyperoxia before cardiac arrest is sparsely investigated. Our aim was to assess the association between excessive oxygen administration before cardiac arrest and the extent of subsequent myocardial injury. METHODS: We performed a retrospective study including patients who had in-hospital cardiac arrest during 2014 in the Capital Region of Denmark. We excluded patients without peripheral oxygen saturation measurements within 48 hours before cardiac arrest. Patients were divided in three groups of pre-arrest oxygen exposure, based on average peripheral oxygen saturation and supplemental oxygen. Primary outcome was peak troponin concentration within 30 days. Secondary outcomes included 30-day mortality. Data were analyzed using multiple logistic regression and Wilcoxon rank sum test. RESULTS: Of 163 patients with cardiac arrest, 28 had excessive oxygen administration (17%), 105 had normal oxygen administration (64%) and 30 had insufficient oxygen administration (18%) before cardiac arrest. Peak troponin was median 224 ng/L in the excessive oxygen administration group vs 365 ng/L in the normal oxygen administration group (P = .54); 20 of 28 (71%) in the excessive oxygen administration group died within 30 days compared to 54 of 105 (51%) in the normal oxygen administration group. (OR 1.87, 95% CI 0.56-6.19) CONCLUSIONS: Excessive oxygen administration within 48 hours before in-hospital cardiac arrest was not statistically associated with significantly higher peak troponin or mortality.

Serum Biomarkers as Prognostic Factors for Metastatic Sarcoma.

AIMS: To investigate the prognostic value of combining inflammatory biomarkers in a prognostic index (Aarhus composite biomarker score: ACBS), adjusted for known confounders, including comorbidity, in patients with metastatic sarcoma. MATERIALS AND METHODS: All patients diagnosed with metastatic sarcoma from 1993 until 2008 were extracted from the Aarhus sarcoma database. The levels of serum albumin, C-reactive protein, serum sodium, haemoglobin, neutrophils and lymphocytes were collected. ACBS as well as the neutrophil to lymphocyte ratio (NLR), Glasgow prognostic score (GPS) and a combined score of GPS and NLR known as CNG were calculated. The prognostic importance of the biomarkers on disease-specific mortality was analysed. Adjustments were made for age, comorbidity, histological type and site of metastasis using the Cox proportional hazard model. Harrell's concordance index (C-index) was used to evaluate whether the ACBS adds prognostic information to already known prognostic factors. The data were validated using the bootstrapping method. RESULTS: In total, 265 patients with metastatic sarcoma were included. The 2-year disease-specific mortality was 74% (95% confidence interval 68-80) and 79% (95% confidence interval 68-88) for soft-tissue sarcoma and bone sarcoma, respectively. Comorbidity was present in 21% of soft-tissue sarcoma patients and 13% of the bone sarcoma patients. All six biomarkers were independent prognostic factors. The various scoring systems (NLR, GPS, CNG and ACBS) combining more than one biomarker were also prognostic for disease-specific mortality. CONCLUSION: The biomarker scoring systems are independent prognostic factors for adult patients with metastatic sarcoma. However, a modified ACBS was superior to all the other scoring systems in predicting outcome.

Solitary Fibrous Tumour: A Single Institution Retrospective Study and Further Validation of a Prognostic Risk Assessment System.

AIMS: Solitary fibrous tumour (SFT) is a rare mesenchymal-derived neoplasm that can arise in any anatomical location in the body. SFT rarely metastasises, but aggressive behaviour is seen in a minority of cases, and relapses can occur several years after treatment. It would be a clinical advantage if high-risk patients could be identified before treatment. MATERIALS AND METHODS: We retrospectively analysed a population-based cohort of SFT to describe treatment, outcome, prognostic factors and to further validate a previously published risk assessment tool (D-score) based on age, tumour size and mitotic index. Seventy-two patients diagnosed with SFT in the Central, North and Southern Denmark regions between 1979 and 2013 were included in the study. RESULTS: For patients with localised disease at the time of diagnosis (n = 64) the 5 and 10 year overall survival was 86% (95% confidence interval 74-92) and 65% (95% confidence interval 50-78), respectively. Seventeen of 62 patients (27%) who were in remission after radical treatment developed recurrence with either local or distant disease. The 5 year recurrence-free survival was 83% (95% confidence interval 70-90) and the 10 year was 69% (95% confidence interval 53-81). The 5 year local recurrence-free survival was 96% (95% confidence interval 86-99) and the 10 year was 92% (95% confidence interval 76-96). The median time to both overall recurrence and local recurrence was 4.3 years. Metastatic or inoperable SFT had a poor prognosis with a median overall survival of 8.4 months (range 3.6-26.4) and a 5 year overall survival of 11% (95% confidence interval 2-30). A further validation of a risk assessment tool (D-score) confirmed that patients classified as high-risk had a significantly decreased overall survival, with a hazard ratio of 3.7 (95% confidence interval 1.1-12.3). CONCLUSIONS: This study showed that our management and outcome were comparable with other published studies describing SFT and confirmed the value of the D-score as a risk assessment tool. Because of late recurrences, long-term (e.g. 10 years) follow-up for moderate- and high-risk patients is recommended.

Specific Ion Effects on the Interaction of Hydrophobic and Hydrophilic Self-Assembled Monolayers.

Interactions between mineral surfaces and organic molecules are fundamental to life processes. The presence of cations in natural environments can change the behavior of organic compounds and thus alter the mineral-organic interfaces. We investigated the influence of Na+, Mg2+, Ca2+, Sr2+, and Ba2+ on the interaction between two models, self-assembled monolayers, that were tailored to have hydrophobic -CH3 or hydrophilic -COO(H) terminations. Atomic force microscopy in chemical force mapping mode, where the tips were functionalized with the same terminations, was used to measure adhesion forces between the tip and substrate surfaces, to gather fundamental information about the role of these cations in the behavior of organic compounds and the surfaces where they adsorb. Adhesion force between hydrophobic surfaces in 0.5 M NaCl solutions that contained 0.012 M divalent cations did not change, regardless of the ionic potential, that is, the charge per unit radius, of the cation. For systems where one or the other surface was functionalized with carboxylate, -COO(H), mostly in its deprotonated form, -COO-, a reproducible change in the adhesion force was observed for each of the ions. The trend of increasing adhesion force followed the pattern: Na+ ≈ Mg2+ < Sr2+ < Ca2+ < Ba2+, suggesting that ionic potential, thus hydrated radius, controls the interaction. The presence of a -CH3 surface in the asymmetric system leads to lower adhesion forces than in the hydrophilic system, whereas the ionic trend remains the same. Although specific ion effects are felt in both systems, the lower adhesion force in the asymmetric system, compared with the hydrophilic system, implies that the -CH3 surface plays an important role.

The association between pre-operative sepsis and 30-day mortality in hip fracture patients-A cohort study.

BACKGROUND: Post-operative sepsis considerably increases mortality, but the extent of pre-operative sepsis in hip fracture patients and its consequences are sparsely elucidated. The aim of this study was to assess the association between pre-operative sepsis and 30-day mortality after hip fracture surgery. METHODS: We conducted a retrospective analysis of data collected among 1894 patients who underwent hip fracture surgery in the Capital Region of Denmark in 2014 (NCT03201679). Data on vital signs, cultures and laboratory data were obtained. Sepsis was defined as a positive culture of any kind and presence of systemic inflammatory response syndrome within 24 hours and was assessed within 72 hours before surgery and 30 days post-operatively. Primary outcome was 30-day mortality. Secondary outcomes included length of hospital stay and admission to intensive care unit. RESULTS: A total of 144 (7.6%) of the hip fracture patients met the criteria for pre-operative sepsis. The 30-day mortality was 13.9% in patients with pre-operative sepsis as compared to 9.0% in those without (OR 1.69, 95% CI [1.00; 2.85], P = .08). Patients with pre-operative sepsis had longer hospital stays (median 10 days vs 9 days, mean difference 2.1 [SD 9.4] days, P = .03), and higher frequency of ICU admission (11.1% vs 2.7%, OR 4.15, 95% CI [2.19; 7.87], P < .0001). CONCLUSION: Pre-operative sepsis in hip fracture patients was associated with an increased length of hospital stay and tended to increase mortality. Pre-operative sepsis in hip fracture patients merits more intensive surveillance and increased attention to timely treatment.

The nucleoside analog GS-441524 strongly inhibits feline infectious peritonitis (FIP) virus in tissue culture and experimental cat infection studies.

Feline infectious peritonitis (FIP) is a common and highly lethal coronavirus disease of domestic cats. Recent studies of diseases caused by several RNA viruses in people and other species indicate that antiviral therapy may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor to a pharmacologically active nucleoside triphosphate molecule. These analogs act as an alternative substrate and RNA-chain terminator of viral RNA dependent RNA polymerase. We determined that GS-441524 was non-toxic in feline cells at concentrations as high as 100 uM and effectively inhibited FIPV replication in cultured CRFK cells and in naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats in vivo and established a dosage that would sustain effective blood levels for 24 h. In an experimental FIPV infection of cats, GS-441524 treatment caused a rapid reversal of disease signs and return to normality with as little as two weeks of treatment in 10/10 cats and with no apparent toxicity.

Modifications of the National Early Warning Score for patients with chronic respiratory disease.

BACKGROUND: The National Early Warning Score (NEWS) uses physiological variables to detect deterioration in hospitalized patients. However, patients with chronic respiratory disease may have abnormal variables not requiring interventions. We studied how the Capital Region of Denmark NEWS Override System (CROS), the Chronic Respiratory Early Warning Score (CREWS) and the Salford NEWS (S-NEWS) affected NEWS total scores and NEWS performance. METHODS: In an observational study, we included patients with chronic respiratory disease. The frequency of use of CROS and the NEWS total score changes caused by CROS, CREWS and S-NEWS were described. NEWS, CROS, CREWS and S-NEWS were compared using 48-h mortality and intensive care unit (ICU) admission within 48 h as outcomes. RESULTS: We studied 11,266 patients during 25,978 admissions; the use of CROS lowered NEWS total scores in 40% of included patients. CROS, CREWS and S-NEWS had lower sensitivities than NEWS for 48-h mortality and ICU admission. Specificities and PPV were higher. CROS, CREWS and S-NEWS downgraded, respectively, 51.5%, 44.9% and 32.8% of the NEWS total scores from the 'mandatory doctor presence' and 'immediate doctor presence and specialist consultation' total score intervals to lower intervals. CONCLUSION: Capital Region of Denmark NEWS Override System was frequently used in patients with chronic respiratory disease. CROS, CREWS and S-NEWS reduced sensitivity for 48-h mortality and ICU admission. Using the methodology prevalent in the NEWS literature, we cannot conclude on the safety of these systems. Future prospective studies should investigate the balance between detection rate and alarm fatigue of different systems, or use controlled designs and patient-centred outcomes.

Genetically determined high activity of IL-12 and IL-18 in ulcerative colitis and TLR5 in Crohns disease were associated with non-response to anti-TNF therapy.

Anti-tumour necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. A recent study indicated that genetically determined high activity of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6 and interferon gamma (IFN-γ), are associated with non-response to anti-TNF therapy. Using a candidate gene approach, 21 functional single-nucleotide polymorphisms (SNPs) in 14 genes in the Toll-like receptors, the inflammasome and the IFNG pathways were assessed in 482 and 256 prior anti-TNF naïve Danish patients with CD and UC, respectively. The results were analysed using logistic regression (adjusted for age and gender). Eight functional SNPs were associated with anti-TNF response either among patients with CD (TLR5 (rs5744174) and IFNGR2 (rs8126756)), UC (IL12B (rs3212217), IL18 (rs1946518), IFNGR1 (rs2234711), TBX21 (rs17250932) and JAK2 (rs12343867)) or in the combined cohort of patient with CD and UC (IBD) (NLRP3 (rs10754558), IL12B (rs3212217) and IFNGR1 (rs2234711)) (P<0.05). Only the association with heterozygous genotype of IL12B (rs3212217) (OR: 0.24, 95% CI: 0.11-0.53, P=0.008) among patients with UC withstood Bonferroni correction for multiple testing. In conclusion, Our results suggest that SNPs associated with genetically determined high activity of TLR5 among patients with CD and genetically determined high IL-12 and IL-18 levels among patients with UC were associated with non-response. Further studies will evaluate whether these genes may help stratifying patients according to the expected response to anti-TNF treatment.