[Fitness, body composition and quality of life following cancer treatment]. / Þrek, holdafar og heilsutengd lífsgæði eftir krabbameinsaðgerð

INTRODUCTION: Five-year survival of people diagnosed with cancer has increased in past decades. Knowledge of the long-term effects of cancer treatment on fitness, body composition and health related quality of life (HR-QoL) is important for cancer patients. The study aimed to evaluate body composition, HR-QoL and personality D of people post cancer treatment in the last 10 years; and to observe whether fitness was correlated with body composition and HR-QoL amongst them. MATERIAL AND METHODS: Eighty participants 25 - 77 y/o of both genders in remission from cancer answered questionnaires on HR-QoL (SF-36v2 and EQ-5D-3L), personality D (DS14), general health, lifestyle and cancer treatment. Participants had their blood pressure measured, conducted the 6-minute walk test (6MWT) and had their body composition meas-ured: body mass index, body fat percentage, waist and hip circumferences. SPSS was used for statistical analysis. RESULTS: Approximately 2/3 of the participants had body composition over recommended values. Over half were overweight or obese. 66.3% had waist circumference over recommended values and 45.0% had waist/hip ratio over recommended values. 6MWT average distance was 634 m +/- 83 m. Significant correlation (p<0.05) was found between 6MWT and body composition and most categories of HR-QoL. -Increased fitness correlated with better body composition and higher HR-QoL. Only 13.8% of participants showed personality D. CONCLUSION: Cancer survivor's body composition is generally not at its best. It is important that people diagnosed with cancer are informed on the importance of healthy body composition. Fitness is an indicator for HR-QoL and body composition of cancer survivors.

Treatment of idiopathic pulmonary fibrosis: a position paper from a Nordic expert group.

Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease occurring in adults. In the last decade, the results of a number of clinical trials based on the updated disease classification have been published. The registration of pirfenidone and nintedanib, the first two pharmacological treatment options approved for IPF, marks a new chapter in the management of patients with this disease. Other nonpharmacological treatments such as lung transplantation, rehabilitation and palliation have also been shown to be beneficial for these patients. In this review, past and present management is discussed based on a comprehensive literature search. A treatment algorithm is presented based on available evidence and our overall clinical experience. In addition, unmet needs with regard to treatment are highlighted and discussed. We describe the development of various treatment options for IPF from the first consensus to recent guidelines based on evidence from large-scale, multinational, randomized clinical trials, which have led to registration of the first drugs for IPF.

Increased warm water intrusions could cause mass loss in East Antarctica during the next 200 years.

The East Antarctic Ice Sheet (EAIS) is currently surrounded by relatively cool water, but climatic shifts have the potential to increase basal melting via intrusions of warm modified Circumpolar Deep Water (mCDW) onto the continental shelf. Here we use an ice sheet model to show that under the current ocean regime, with only limited intrusions of mCDW, the EAIS will likely gain mass over the next 200 years due to the increased precipitation from a warming atmosphere outweighing increased ice discharge due to ice-shelf melting. However, if the ocean regime were to become dominated by greater mCDW intrusions, the EAIS would have a negative mass balance, contributing up to 48 mm of SLE over this time period. Our modelling finds George V Land to be particularly at risk to increased ocean induced melting. With warmer oceans, we also find that a mid range RCP4.5 emissions scenario is likely to result in a more negative mass balance than a high RCP8.5 emissions scenario, as the relative difference between increased precipitation due to a warming atmosphere and increased ice discharge due to a warming ocean is more negative in the mid range RCP4.5 emission scenario.

Proteomic associations with forced expiratory volume - a Mendelian randomisation study.

A decline in forced expiratory volume (FEV1) is a hallmark of obstructive respiratory diseases, an important cause of morbidity among the elderly. While some data exist on biomarkers that are related to FEV1, we sought to do a systematic analysis of causal relations of biomarkers with FEV1. Data from the general population-based AGES-Reykjavik study were used. Proteomic measurements were done using 4,782 DNA aptamers (SOMAmers). Data from 1,648 participants with spirometric data were used to assess the association of SOMAmer measurements with FEV1 using linear regression. Bi-directional Mendelian randomisation (MR) analyses were done to assess causal relations of observationally associated SOMAmers with FEV1, using genotype and SOMAmer data from 5,368 AGES-Reykjavik participants and genetic associations with FEV1 from a publicly available GWAS (n = 400,102). In observational analyses, 473 SOMAmers were associated with FEV1 after multiple testing adjustment. The most significant were R-Spondin 4, Alkaline Phosphatase, Placental Like 2 and Retinoic Acid Receptor Responder 2. Of the 235 SOMAmers with genetic data, eight were associated with FEV1 in MR analyses. Three were directionally consistent with the observational estimate, Thrombospondin 2 (THBS2), Endoplasmic Reticulum Oxidoreductase 1 Beta and Apolipoprotein M. THBS2 was further supported by a colocalization analysis. Analyses in the reverse direction, testing whether changes in SOMAmer levels were caused by changes in FEV1, were performed but no significant associations were found after multiple testing adjustments. In summary, this large scale proteogenomic analyses of FEV1 reveals protein markers of FEV1, as well as several proteins with potential causality to lung function.

Fortnightly variations in the flow velocity of Rutford Ice Stream, West Antarctica.

Most of the ice lost from the Antarctic ice sheet passes through a few fast-flowing and highly dynamic ice streams. Quantifying temporal variations in flow in these ice streams, and understanding their causes, is a prerequisite for estimating the potential contribution of the Antarctic ice sheet to global sea-level change. Here I show that surface velocities on a major West Antarctic Ice Stream, Rutford Ice Stream, vary periodically by about 20 per cent every two weeks as a result of tidal forcing. Tidally induced motion on ice streams has previously been thought to be limited to diurnal or even shorter-term variations. The existence of strong fortnightly variations in flow demonstrates the potential pitfalls of using repeated velocity measurements over intervals of days to infer long-term change.

High spatial and temporal variability in Antarctic ice discharge linked to ice shelf buttressing and bed geometry.

Antarctica's contribution to global mean sea level rise has been driven by an increase in ice discharge into the oceans. The rate of change and the mechanisms that drive variability in ice discharge are therefore important to consider in the context of projected future warming. Here, we report observations of both decadal trends and inter-annual variability in ice discharge across the Antarctic Ice Sheet at a variety of spatial scales that range from large drainage basins to individual outlet glacier catchments. Overall, we find a 37 ± 11 Gt year-1 increase in discharge between 1999 and 2010, but a much smaller increase of 4 ± 8 Gt year-1 between 2010 and 2018. Furthermore, comparisons reveal that neighbouring outlet glaciers can behave synchronously, but others show opposing trends, despite their close proximity. We link this spatial and temporal variability to changes in ice shelf buttressing and the modulating effect of local glacier geometry.

Evaluating the Feasibility of a Digital Therapeutic Program for Patients With Cancer During Active Treatment: Pre-Post Interventional Study.

BACKGROUND: Increasing evidence shows that lifestyle interventions can improve the symptoms, quality of life (QoL), and even overall survival of patients with cancer. Digital therapeutics (DTx) can help implement behavioral modifications and empower patients through education, lifestyle support, and remote symptom monitoring. OBJECTIVE: We aimed to test the feasibility of a DTx program for patients with cancer, as measured by engagement, retention, and acceptability. In addition, we explored the effects of the program on cancer-related QoL. METHODS: We conducted a 4-week single-arm trial in Iceland, where DTx was delivered through a smartphone app. The intervention consisted of patient education about mindfulness, sleep, stress, and nutrition; lifestyle coaching; and the completion of daily missions for tracking physical activity and exercise, reporting patient-reported outcomes (PROs), practicing mindfulness, and logging healthy food intake. Information on program engagement and retention, step goal attainment, as well as PROs were collected throughout the study. QoL was measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 at baseline and follow-up. RESULTS: In total, 30 patients with cancer undergoing active therapy were enrolled, and 29 registered in the app (23 female, 18 with breast cancer; mean age 52.6, SD 11.5 years). Overall, 97% (28/29) of participants were active in 3 of the 4 weeks and completed the pre- and postprogram questionnaires. The weekly active days (median) were 6.8 (IQR 5.8-6.8), and 72% (21/29) of participants were active at least 5 days a week. Users interacted with the app on average 7.7 (SD 1.9) times per day. On week 1, all 29 participants used the step counter and logged an average of 20,306 steps; 21 (72%) participants reached their step goals of at least 3000 steps per day. On week 4, of the 28 active users, 27 (96%) were still logging their steps, with 19 (68%) reaching their step goals. Of the 28 participants who completed the satisfaction questionnaire, 25 (89%) were likely to recommend the program, 23 (82%) said the program helped them deal with the disease, and 24 (86%) said it helped them remember their medication. QoL assessment showed that the average global health status, functioning, and symptom burden remained stable from baseline to follow-up. In all, 50% (14/28) of participants reported less pain, and the average pain score decreased from 31 (SD 20.1) to 22.6 (SD 23.2; P=.16). There was no significant change in PROs on the quality of sleep, energy, and stress levels from the first to the last week. CONCLUSIONS: The high retention, engagement, and acceptability found in this study demonstrate that multidisciplinary DTx is feasible for patients with cancer. A longer, full-scale randomized controlled trial is currently being planned to evaluate the efficacy of the intervention.

Downregulation of bactericidal peptides in enteric infections: a novel immune escape mechanism with bacterial DNA as a potential regulator.

Antibacterial peptides are active defense components of innate immunity. Several studies confirm their importance at epithelial surfaces as immediate barrier effectors in preventing infection. Here we report that early in Shigella spp. infections, expression of the antibacterial peptides LL-37 and human beta-defensin-1 is reduced or turned off. The downregulation is detected in biopsies from patients with bacillary dysenteries and in Shigella- infected cell cultures of epithelial and monocyte origin. This downregulation of immediate defense effectors might promote bacterial adherence and invasion into host epithelium and could be an important virulence parameter. Analyses of bacterial molecules causing the downregulation indicate Shigella plasmid DNA as one mediator.

Migration along orthodromic sun compass routes by arctic birds.

Flight directions of birds migrating at high geographic and magnetic latitudes can be used to test bird orientation by celestial or geomagnetic compass systems under polar conditions. Migration patterns of arctic shorebirds, revealed by tracking radar studies during an icebreaker expedition along the Northwest Passage in 1999, support predicted sun compass trajectories but cannot be reconciled with orientation along either geographic or magnetic loxodromes (rhumb lines). Sun compass routes are similar to orthodromes (great circle routes) at high latitudes, showing changing geographic courses as the birds traverse longitudes and their internal clock gets out of phase with local time. These routes bring the shorebirds from high arctic Canada to the east coast of North America, from which they make transoceanic flights to South America. The observations are also consistent with a migration link between Siberia and the Beaufort Sea region by way of sun compass routes across the Arctic Ocean.

Comment on "Friction at the bed does not control fast glacier flow".

Stearns and van der Veen (Reports, 20 July 2018, p. 273) conclude that fast glacier sliding is independent of basal drag (friction), even where drag balances most of the driving stress. This conclusion raises fundamental physical issues, the most striking of which is that sliding velocity would be independent of stresses imparted through the ice column, including gravitational driving stress.

Interferon-gamma is necessary for the expression of hypersensitivity pneumonitis.

Farmers lung disease is a common form of hypersensitivity pneumonitis (HP) and is characterized by inflammation and granuloma formation in the lung. Interferon-gamma is important for the expression of granulomatous diseases caused by infectious agents; however, the role this mediator in regulating expression of the granulomatous response to inhaled antigen is not known. To evaluate this, we compared the response to inhaled antigen of mice that do not express the gene coding for interferon-gamma (GKO) with that of their normal littermates (WT). GKO and WT mice on a BALB/c background were exposed to 150 microg of the thermophilic bacteria Saccharopolyspora rectivirgula or saline alone, for three consecutive days a week, for 3 wk. After exposure to antigen, WT mice developed a marked granulomatous inflammation associated with an increase in lung weight and numbers of cells in bronchoalveolar lavage fluid (BAL). Although GKO mice also exhibited an increase in lung weight and numbers of cells in BAL fluid, they developed minimal inflammation and no granulomas after a similar exposure to antigen. To further evaluate if the lack of a response to antigen in GKO mice was due to lack of IFN-gamma, we replaced this mediator via intraperitoneal injections. When given replacement IFN-gamma, the GKO mice developed granulomatous inflammation in the lung. These studies show that IFN-gamma is essential for the expression of hypersensitivity pneumonitis.

Host antimicrobial defence peptides in human disease.

Antimicrobial peptides or host defence peptides are endogenous peptide antibiotics, which have been confirmed as an essential part of the immune system. Apart from direct killing of bacteria, a role for the peptides in antiviral and immunomodulatory functions has recently been claimed. In this chapter we have focused on the host contact with microbes, where these host defence peptides are key players. The interplay with commensals and pathogens in relation to antimicrobial peptide expression is discussed, with specific emphasis on the respiratory and the alimentary systems. A possible novel difference in epithelial interactions between commensals and pathogens is considered in relation to disease.

Clinical features in secondary and cryptogenic organising pneumonia.

SETTING: The clinical differences between cryptogenic organising pneumonia (COP) and secondary organising pneumonia (OP) have not been studied well. OBJECTIVE: To compare clinical features in COP and secondary OP. DESIGN: Causes, clinical features, treatment, radiographic studies and pathology were studied. RESULTS: After re-evaluation, 104 patients fulfilled the diagnostic criteria, 58 for COP and 46 for secondary OP. The mean age was 68 years. Most of the patients were smokers (79/104). Infections were the most common causes of secondary OP (21/46). Cough was the most common symptom and crackles the most common sign. Crackles were more common in patients with secondary OP (P = 0.02). Transbronchial biopsy was the diagnostic test in 81/104 cases. Most patients had lowered partial oxygen pressure (PO(2)) and mildly restrictive spirometry, with no differences between the two groups. Radiographic features were similar. Corticosteroids were the treatment in 70% of the patients, but 27% received no pharmacological treatment. The average initial dose of steroids was 42 mg prednisolone, and was similar for both groups. Relapses were seen in 20% of cases, with no difference between the two groups. CONCLUSION: There were no major differences in clinical features of COP and secondary OP, except that crackles were more common in secondary OP.

Potent Inducers of Endogenous Antimicrobial Peptides for Host Directed Therapy of Infections.

A new concept for treatment of infections is induction of our own antimicrobial peptides and the presented novel class of inducer, aroylated phenylenediamines (APDs), gives up to 20 to 30-fold induction of the human antimicrobial peptide LL-37, in vitro. In addition, oral administration of an APD in a rabbit model of Shigellosis resulted in recovery from the infection in a few days implying that APD's are promising candidates for treatment of infections.

Noninfectious constrictive pericarditis in a heart transplant recipient.

Acute rejection, infection, and allograft coronary artery disease have been recognized as the major causes of postoperative morbidity and mortality in cardiac transplant patients. More recently, pericardial and mediastinal complications have been recognized as a more common complication than previously believed. We describe a case of a heart transplant recipient admitted for apparent congestive heart failure exacerbation who was unresponsive to standard medical management of congestive heart failure and rejection. After further invasive evaluation, it was discovered the patient's condition was attributable to posttransplantation constrictive pericarditis. It is appropriate to consider this diagnosis in any postcardiac surgery (especially heart transplant recipients) in patients presenting with congestive heart failure exacerbations refractory to usual medical management.

Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus.

Cathelicidins are a family of peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides play a part in the protection of skin against wound infections, the anti-microbial activity of LL-37 and CRAMP was determined against the common wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of cathelicidins in human and murine skin after sterile incision, or in mouse following infection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide. Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that both LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins are well suited to provide defense against infections due to group A Streptococcus, and represent an important element of cutaneous innate immunity.

Interaction of mouse placental lactogens and androgens in regulating progesterone release in cultured mouse luteal cells.

Pituitary hormones are essential for the maintenance of the corpus luteum in the pregnant mouse during the first half of gestation. Thereafter, hormones from the placenta take over the luteotropic role of the pituitary hormones. Mouse placental lactogen-I (mPL-I) and mPL-II, two PRL-like hormones produced in the placenta, are probably necessary for the maintenance of the corpus luteum in the latter half of pregnancy. A culture system of luteal cells from pregnant mice was developed to investigate the role of hormones from the placenta that may be important for the function of the corpus luteum. Mice were killed on days 10, 14, and 18 of pregnancy, and the corpora lutea were excised from the ovaries and digested in 0.1% collagenase, 0.002% DNase for 1 h. The resulting luteal cell suspension was plated onto 96-well plates coated with fibronectin (1 x 10(5) cells/well) and cultured for 1-3 days. Medium was changed daily. The cells were treated with various concentrations and combinations of mPL-I, mPL-II, mouse PRL, androstenedione, dihydrotestosterone, 17beta-estradiol (E2), testosterone, hydroxyflutamide, cycloheximide, actinomycin D, and fadrozole to study the effects of these different treatments on progesterone (P4) production. The three lactogens (mPL-I, mPL-II, and mouse PRL) all stimulated the release of P4 from the luteal cells. The potency of the lactogens was similar and did not depend on the stage of pregnancy at which the luteal tissue was obtained. However, the responsiveness of the cells to all hormone-stimulated P4 release was gradually reduced the later in pregnancy the tissue was collected. Androgens also stimulated the release of P4 from the luteal cells, and when administered together, the lactogens and the androgens acted synergistically to stimulate P4 release. The androgens acted directly but not through conversion to E2, as determined by the findings that 1) the effects of the androgens could not be reproduced by E2 administration, 2) nonaromatizable androgen dihydrotestosterone was as effective as aromatizable androgens, and 3) aromatase inhibitor did not prevent the action of the androgens to stimulate the P4 release. The effect of the androgens on the P4 release was rapid, occurring within 15 min of hormone administration. It was not prevented by inhibitors of protein and RNA synthesis, and the intracellular androgen receptor antagonist hydroxyflutamide did not affect the androgen action. Therefore, the androgen effects were not mediated through the intracellular androgen receptor and de novo protein synthesis was not needed for androgen-stimulated P4 release.

Fertility in patients with epilepsy: a population-based study.

OBJECTIVE: Several studies have suggested that people with epilepsy have altered fertility, but comparison groups have been imperfect. METHOD: A retrospective cohort study of all live births to 209 incident patients with epilepsy in Iceland from 1960 to 1964 and live births to 418 age- (to the closest day of birth) and gender-matched residents without epilepsy. RESULTS: Incident patients with epilepsy had an average of 2.0 children; the controls also had an average of 2.0 children. When people with idiopathic/cryptogenic epilepsy were compared with controls, there was no difference in number of children or number of partners overall, nor were there differences when stratified by seizure type or age at diagnosis. There was a deficit in the number of children among patients with remote symptomatic epilepsy. This was attributed to a reduced number of offspring of patients with mental retardation (MR) or cerebral palsy (CP) when compared with their controls. CONCLUSION: There is no evidence of altered fertility among people with idiopathic/cryptogenic epilepsy or remote symptomatic epilepsy (other than MR or CP) within this population-based incidence cohort.

A population-based study of prognosis of ruptured cerebral aneurysm: mortality and recurrence of subarachnoid hemorrhage.

OBJECTIVE: To determine the risk of recurrent subarachnoid hemorrhage (SAH), mortality, and relative survivorship following SAH caused by ruptured cerebral aneurysm (RCA). DESIGN/METHODS: The 86 individuals with a first diagnosis of SAH caused by RCA in Iceland from 1958 through 1968 were followed a minimum of 24 years (range, 24 to 32.5 years) or until death to determine mortality and to identify those with recurrent SAH. RESULTS: Thirty-eight patients (44%) died within 30 days of the index event. Two additional (both comatose from onset of ictus) died in the following month. There were no deaths between 3 and 6 months after onset. Based upon the age/gender-specific person years of observation for the population of Iceland, the Standardized Mortality Ratio for the 44 surgically treated patients surviving 6 months was 1.3. Those neurologically normal or with only mild impairment at 6 months had no identified increase in mortality. Excess mortality that was limited to individuals with severe neurologic deficit at 6 months could be identified through the first 10 years after onset. Two 6-month survivors experienced recurrent SAH. CONCLUSIONS: Early mortality is high (47%) in patients with RCA. In patients operated on for RCA and surviving 6 months, recurrent SAH occurred in 5%. Survivorship among patients surgically treated and neurologically normal or with mild residual neurologic impairment at 6 months following presentation was similar to that expected in the general population. Survivorship among patients surgically treated who had severe residual neurologic impairment at 6 months was significantly reduced.