Assessment of postoperative circulating tumour DNA to predict early recurrence in patients with stage I-III right-sided colon cancer: prospective observational study.

BACKGROUND: Right-sided colon cancer (RCC) differs in mutation profile and risk of recurrence compared to distal colon cancer. Circulating tumour DNA (ctDNA) present after surgery can identify patients with residual disease after curative surgery and predict risk of early recurrence. METHODS: This is a prospective observational biomarker trial with exploration of ctDNA in 50 non-metastatic RCC patients for which oncological right-sided colectomy was performed. Blood samples were collected preoperatively, within 1 month post surgery, 3 months (not mandatory), 6 months and every 6 months thereafter. Plasma cell free DNA and/or tumour was investigated for cancer-related mutations by the next-generation sequencing (NGS) panel AVENIO surveillance specifically designed for ctDNA analysis. Detected mutations were quantified using digital droplet PCR (ddPCR) for follow-up. Recurrence-free survival was explored. RESULTS: 50 patients were recruited. Somatic cancer-related mutations were detected in 47/50 patients. ddPCR validated results from NGS for 27/34 (plasma) and 72/72 samples (tumour). Preoperative ctDNA was detected in 31/47 of the stage I/III patients and the majority of ctDNA positive patients showed reduction of ctDNA after surgery (27/31). ctDNA-positive patients at first postoperative sample had high recurrence risk compared to patients without measurable ctDNA (adjusted hazard ratio: 172.91; 95% c.i.: 8.70 to 3437.24; P: 0.001). CONCLUSION: ctDNA was detectable in most patients with non-metastatic RCC before surgery. Positive postoperative ctDNA was strongly associated with early recurrence. Detectable postoperative ctDNA is a prognostic factor with high (100%) positive predictive value for recurrence in this cohort of non-metastatic RCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03776591.

Complications after open and laparoscopic right-sided colectomy with central lymphadenectomy for colon cancer: randomized controlled trial.

BACKGROUND: A central lymphadenectomy in right-sided colon cancer involves dissection along the superior mesenteric axis, but the extent is debated due to a lack of consensus and the fear of major complications. This randomized controlled trial compared the rate of postoperative morbidity in patients undergoing laparoscopic versus open right-sided colectomy with central lymphadenectomy. METHODS: This open, prospective, randomized controlled trial compared patients operated on with open and laparoscopic right-sided colectomy (cStages I-III) with a central lymphadenectomy at two Norwegian institutions between October 2016 and December 2021. Dissections were conducted along the superior mesenteric vein in the laparoscopic group, and along the left anterior border of the superior mesenteric artery in the open group, both according to complete mesocolic excision principles. Surgery was standardized and performed by three experienced surgeons for each study group. The primary outcome of interest was to measure postoperative 30-day complications (Clavien-Dindo ≥ grade II). RESULTS: Of 273 eligible patients, 135 were randomized and 128 analysed (63 operated on with open and 65 using laparoscopic procedures). Postoperative complications occurred in 42.8 per cent of the patients treated with open and 38.4 per cent of the patients treated using laparoscopic surgery, P = 0.372. The incidence of Clavien-Dindo grade IIIb complications was 7.9 per cent in the open versus 4.6 per cent in the laparoscopic group, P = 0.341. There were no grade IV or V complications, and no re-operations due to anastomotic leakages. There was no significant difference in the mean(s.e.m.) number of removed lymph nodes (open versus laparoscopic respectively: 31.9(1.8) versus 29.3(1.3); P = 0.235). CONCLUSION: There was no significant difference in complications between the two groups. Standardized oncologic right-sided colectomy with central lymphadenectomy along the mesenterial root was performed safely, both open and laparoscopic, with incidence of major complications ranging between 4.6 and 7.9 per cent and no re-operations for anastomotic leakage. Radicality in terms of lymphadenectomy was comparable between the two groups.Registration number: NCT03776591 (http://www.clinicaltrials.gov).

Prevalence of atherosclerosis and association with 5-year outcome: The Norwegian Stroke in the Young Study.

Objectives: We studied the prevalence of atherosclerosis among ischaemic stroke patients ≤60 years and controls at the time of the index stroke, and its association with occurrence of new cardiovascular events (CVEs) and mortality at a 5-year follow-up. Methods: Prevalent atherosclerosis was assessed for 385 patients and 260 controls in seven vascular areas by electrocardiogram (ECG), ankle-arm index (AAI) and measurement of right and left carotid and femoral intima-media thickness (cIMT and fIMT) and abdominal aorta plaques (AAP). Clinical end-points were any new CVE (stroke, angina, myocardial infarction or peripheral arterial disease) or death from any cause at 5-year follow-up. All results were sex- and age-adjusted; logistic regression and Cox proportional hazards models were applied. Results: Young patients ≤49 years had prevalent atherosclerosis in 1/2 of males and 1/3 of females. Compared with controls, young female patients showed significantly higher prevalent atherosclerosis, p = 0.024. Ischaemic ECG and mean cIMT were higher in young and middle-aged female patients (p = 0.044, p = 0.020, p = 0.023 and p <0.001, respectively). Mean fIMT was higher in middle-aged female patients (p <0.001). Cardiovascular events were associated with ischaemic ECG; AAI ≤0.9, fIMT ≥0.9 mm and increased number of areas with atherosclerosis (NAA) among patients, and with AAP, cIMT ≥0.9 mm, fIMT ≥0.9 mm and NAA among controls. Mortality was associated with higher age, ischaemic ECG and NAA among patients, and cIMT ≥0.9 mm among controls. Conclusion: Atherosclerosis is highly prevalent even in young stroke patients. Some areas and increasing NAA are associated with CVEs and death.

Can serum GAD65 antibody levels predict neurological disease or cancer?

The clinical relevance of antibodies that bind to glutamic acid decarboxylase 65 (GAD65) is controversial regarding diagnostic utility in screening for neurological disease or cancer. We did a retrospective study of 3152 GAD65 antibody-positive patients to examine whether analysis of the antibody levels could predict neurological disease or cancer. Serum GAD65 antibody levels were not associated with any of the following groups: neurological disease, neurological disease and diabetes, diabetes only, no neurological diagnosis and no diabetes mellitus, or cancer. Analysis of serum GAD65 antibody levels had no prognostic value in neurological disease or cancer. GAD65 antibodies should therefore be measured in selective cases of autoimmune neurological diseases.

Nonsupine Positioning after Macular Hole Surgery: A Prospective Multicenter Study.

PURPOSE: To evaluate the postoperative closure rate of full-thickness macular holes (MHs) after nonsupine positioning, which means that the patients avoid upward gaze and a supine sleeping position, and to investigate the correlation between postoperative positioning compliance and closure rate. DESIGN: Prospective, multicenter study (ClinicalTrials.gov identifier, NCT02295943). PARTICIPANTS: Patients undergoing primary surgery for primary MH. METHODS: Patients underwent pars plana vitrectomy with internal limiting membrane peeling and sulfur hexafluoride gas tamponade followed by 3 to 5 days of nonsupine positioning. A positioning measuring device that recorded the time spent in the supine position was attached to patients' forehead after surgery for 24 hours. MAIN OUTCOME MEASURES: Anatomic closure rate of MH at 2 weeks or more after surgery and the time spent in supine position during the first 24 hours after surgery. RESULTS: A total of 205 participants were included, of whom 2 were lost to follow-up. Two hundred two of 203 MHs closed after a single operation, giving a closure rate of 99.5% (95% confidence interval, 97.3%-99.9%). The median time of supine positioning during the first 24 hours was 28 seconds (range, 0:00:00-01:52:28). Because of the very high closure rate, a correlation between positioning compliance and closure rate could not be established. CONCLUSIONS: Pars plana vitrectomy with internal limiting membrane peeling followed by a short-term nonsupine positioning accomplished a very high MH closure rate. Thus, face-down positioning was not necessary to achieve excellent closure rates in this study.

Sense of Coherence, Disability, and Health-Related Quality of Life: A Cross-Sectional Study of Rehabilitation Patients in Norway.

OBJECTIVE: To study relations between sense of coherence (SOC), disability, and mental and physical components of health-related quality of life (HRQOL) among rehabilitation patients. DESIGN: Survey. SETTING: Rehabilitation centers in secondary care. PARTICIPANTS: Patients (N=975) from the Western Norway Health Region consented to participate and had valid data of the main outcome measures. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SOC was measured with the sense of coherence questionnaire (13-item SOC scale [SOC-13]), disability with the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0), and HRQOL with the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: Mean scores ± SD were 62.9±12.3 for SOC-13, 30.8±16.2 for WHODAS 2.0, 32.8±9.6 for SF-36 physical component score, and 43.6±11.8 for SF-36 mental component score. Linear regression analysis showed that increased SOC score was associated with reduced disability scores in the following domains with estimated regression coefficients (95% confidence interval) cognition -0.20 (-0.32 to -0.08), getting along -0.36 (-0.52 to -0.25), and participation -0.23 (-0.36 to -0.11). The fit of 2 structural models with the association from SOC to HRQOL and disability or with disability as a mediator was better for the mental versus the physical component of HRQOL. High SOC increased the mental component of HRQOL, consistent for all diagnostic groups. For both models, good fit was reported for circulatory and less good fit for musculoskeletal diseases. CONCLUSIONS: The results indicate that higher SOC decreases disability in mental domains. The effect of SOC on disability and HRQOL might vary between diagnostic groups. SOC could be a target in rehabilitation, especially among patients with circulatory diseases, but prospective studies are needed.

Multiple electrode aggregometry and thromboelastography in thrombocytopenic patients with haematological malignancies.

BACKGROUND: In thrombocytopenic patients better assessment of bleeding risk than that provided by platelet count alone is required. Multiplate® aggregometry and thromboelastography (TEG) could be used, but information on their role in such patients is limited. The primary aim of this study was to investigate the feasibility of Multiplate® analyses in patients with haematological malignancies. A secondary aim was to explore whether a multiple logistic regression model combining Multiplate®, TEG, clinical and laboratory variables was associated with risk of bleeding. MATERIALS AND METHODS: This was an exploratory, prospective observational study of thrombocytopenic patients with haematological malignancies. Total platelet count (TPC), white blood cell count, C-reactive protein (CRP) level, temperature and bleeding status were recorded daily. TEG and Multiplate® analyses with four agonists were performed on weekdays. RESULTS: Ten patients were enrolled into the study. The median number of days in a study period was 21. Bleeding was observed on 64 of 298 study days. TPC <20×109/L and <10×109/L occurred on 119 and 25 days, respectively. When TPC was <33×109/L, many samples showed no aggregation, regardless of bleeding status. Despite this, the odds of World Health Organization (WHO) grade 2 bleeding decreased significantly as aggregation increased and Multiplate® had a negative predictive value (NPV) of 96% and a positive predictive value (PPV) of 19% for significant bleeding. In the multiple logistic regression model collagen-activated Multiplate® aggregation, TEG angle, TEG reaction time and CRP significantly affected the odds of WHO grade 2 bleeding. The combined model had a NPV of 99% and a PPV of 19%. DISCUSSION: Our findings suggest that the markers of platelet function and haemostasis provided by Multiplate® aggregometry and TEG may add information to support prediction of bleeding, although platelet count still remains the most accessible analysis for routine testing.

Young ischaemic stroke incidence and demographic characteristics - The Norwegian stroke in the young study - A three-generation research program.

INTRODUCTION: Norwegian Stroke in the Young Study (NOR-SYS) is a three-generation research program of young ischaemic stroke. In this study, we assessed ischaemic stroke incidence, education and work status among young stroke patients. Furthermore, we evaluated the participation of family members for future validated information on hereditary cardiovascular events. PATIENTS AND METHODS: Patients aged 15-60 years with radiologically verified acute ischaemic stroke, admitted to Haukeland University Hospital in Bergen, Norway from 2010 to 2015, were included. Patients' partners, common offspring ≥ 18 years and biological parents of patients and partners were invited to participate. Ischaemic stroke incidence was analysed with respect to year, age and sex using multiple logistic regression. RESULTS: A total of 385 patients, 260 partners (80.0%) and 414 offspring (74.6%) were clinically examined. The mean annual ischaemic stroke incidence rate was 30.2 per 100,000. Incidence was higher in men, and the difference was accentuated with increasing age (p = 0.008). There was no sex difference in educational status (p = 0.104) in contrast to work status (p < 0.001) for patients. In all, 84.1% of men worked, and of these, 80.3% are fulltime. In all, 74.4% of women worked, and of these, 52.9% are fulltime. Parents participated by returning a questionnaire. For patients, 91 fathers (55.2%) and 142 mothers (57.3%) participated. For partners, 48 fathers (38.4%) and 68 mothers (40.2%) participated. CONCLUSION: The mean annual incidence rate of young stroke was 30.2 per 100,000, and the incidence rate was higher in men. Work status was high among both sexes. Active participation rates were high for patients, partners and offspring.

Change in pulmonary diffusion capacity in a general population sample over 9 years.

RATIONALE: Data on the change in diffusion capacity of the lung for carbon monoxide (DLCO) over time are limited. We aimed to examine change in DLCO (ΔDLCO) over a 9-year period and its predictors. METHODS: A Norwegian community sample comprising 1,152 subjects aged 18-73 years was examined in 1987 and 1988. Of the 1,109 subjects still alive, 830 (75%) were re-examined in 1996/97. DLCO was measured with the single breath-holding technique. Covariables recorded at baseline included sex, age, height, weight, smoking status, pack years, occupational exposure, educational level, and spirometry. Generalized estimating equations analyses were performed to examine relations between ΔDLCO and the covariables. RESULTS: At baseline, mean [standard deviation (SD)] DLCO was 10.8 (2.4) and 7.8 (1.6) mmol·min(-1)·kPa(-1) in men and women, respectively. Mean (SD) ΔDLCO was -0.24 (1.31) mmol·min(-1)·kPa(-1). ΔDLCO was negatively related to baseline age, DLCO, current smoking, and pack years, and positively related to forced expiratory volume in 1 second (FEV1) and weight. Sex, occupational exposure, and educational level were not related to ΔDLCO. CONCLUSIONS: In a community sample, more rapid decline in DLCO during 9 years of observation time was related to higher age, baseline current smoking, more pack years, larger weight, and lower FEV1.

What is the minimum number of patients for quality control of lung cancer management in Norway?

INTRODUCTION: There are few data available on the optimal number of lung cancer patients needed to generate and compare estimates of quality between units managing lung cancer. The number of lung cancer patients per management unit varies considerably in Norway, where there are 42 hospitals that treated between 1 and 454 lung cancer patients in 2011. AIMS: To estimate the differences in quality indicators that are of sufficient importance to change a pulmonary physician's lung cancer management program, and to estimate the size of the patient samples necessary to detect such differences. METHOD: Twenty-six physicians were asked about the relative differences from a national average of quality indicators that would change their own lung cancer management program. Sample sizes were calculated to give valid estimates of quality of a management unit based on prevalence of quality indicators and minimally important differences (MID). RESULTS: The average MID in quality indicators that would cause a change in management varied from 18% to 24% among 26 chest physicians, depending on the indicator. CONCLUSIONS: To generate precise estimates for quality control of lung cancer care in Norway, the number of management units must be reduced. Given the present willingness of chest physicians to change their procedures for management of lung cancer according to the results of quality control indicators, we recommend a maximum of 10 units with a minimum of 200 incident lung cancer patients per year for each management center.

Adult respiratory outcomes of extreme preterm birth. A regional cohort study.

RATIONALE: Lifetime respiratory function after extremely preterm birth (gestational age≤28 wk or birth weight≤1,000 g) is unknown. OBJECTIVES: To compare changes from 18-25 years of age in respiratory health, lung function, and airway responsiveness in young adults born extremely prematurely to that of term-born control subjects. METHODS: Comprehensive lung function investigations and interviews were conducted in a population-based sample of 25-year-old subjects born extremely prematurely in western Norway in 1982-1985, and in matched term-born control subjects. Comparison was made to similar data collected at 18 years of age. MEASUREMENTS AND MAIN RESULTS: At 25 years of age, 46/51 (90%) eligible subjects born extremely prematurely and 39/46 (85%) control subjects participated. z-Scores for FEV1, forced expiratory flow at 25-75% of vital capacity, and FEV1/FVC were significantly reduced in subjects born extremely prematurely by 1.02, 1.26, and 0.88, respectively, and airway resistance (kPa/L/s) was increased (0.23 versus 0.18). Residual volume to total lung capacity increased with severity of neonatal bronchopulmonary dysplasia. Responsiveness to methacholine (dose-response slope; 3.16 versus 0.85) and bronchial lability index (7.5 versus 4.8%) were increased in subjects born extremely prematurely. Lung function changes from 18 to 25 years and respiratory symptoms were similar in the prematurely born and term-born groups. CONCLUSIONS: Lung function in early adult life was in the normal range in the majority of subjects born extremely prematurely, but methacholine responsiveness was more pronounced than in term-born young adults, suggesting a need for ongoing pulmonary monitoring in this population.

Effect of the World Health Organization checklist on patient outcomes: a stepped wedge cluster randomized controlled trial.

OBJECTIVES: We hypothesized reduction of 30 days' in-hospital morbidity, mortality, and length of stay postimplementation of the World Health Organization's Surgical Safety Checklist (SSC). BACKGROUND: Reductions of morbidity and mortality have been reported after SSC implementation in pre-/postdesigned studies without controls. Here, we report a randomized controlled trial of the SSC. METHODS: A stepped wedge cluster randomized controlled trial was conducted in 2 hospitals. We examined effects on in-hospital complications registered by International Classification of Diseases, Tenth Revision codes, length of stay, and mortality. The SSC intervention was sequentially rolled out in a random order until all 5 clusters-cardiothoracic, neurosurgery, orthopedic, general, and urologic surgery had received the Checklist. Data were prospectively recorded in control and intervention stages during a 10-month period in 2009-2010. RESULTS: A total of 2212 control procedures were compared with 2263 SCC procedures. The complication rates decreased from 19.9% to 11.5% (P < 0.001), with absolute risk reduction 8.4 (95% confidence interval, 6.3-10.5) from the control to the SSC stages. Adjusted for possible confounding factors, the SSC effect on complications remained significant with odds ratio 1.95 (95% confidence interval, 1.59-2.40). Mean length of stay decreased by 0.8 days with SCC utilization (95% confidence interval, 0.11-1.43). In-hospital mortality decreased significantly from 1.9% to 0.2% in 1 of the 2 hospitals post-SSC implementation, but the overall reduction (1.6%-1.0%) across hospitals was not significant. CONCLUSIONS: Implementation of the WHO SSC was associated with robust reduction in morbidity and length of in-hospital stay and some reduction in mortality.

The effect of electroconvulsive therapy on neurocognitive function in treatment-resistant bipolar disorder depression.

OBJECTIVE: To compare the effects of right unilateral (RUL) electroconvulsive therapy (ECT) and algorithm-based pharmacologic treatment (APT) on neurocognitive function in treatment-resistant bipolar disorder depression. METHOD: Inpatients with DSM-IV-TR-diagnosed, treatment-resistant bipolar depression, who were acutely admitted to 1 of the 7 clinical study centers in Norway, were recruited from May 2008 to April 2011 into a prospective, randomized controlled, 6-week acute treatment trial. General neurocognitive function was assessed with the MATRICS Consensus Cognitive Battery (MCCB), and retrograde memory for autobiographical events was assessed with the Autobiographical Memory Interview-Short Form (AMI-SF) before and shortly after (mean = 23.5 days) a trial with either RUL brief-pulse ECT (mean dose = 233.3 mC) or APT. RESULTS: Seventy-three patients entered, and 39 (nECT = 19, nAPT = 20) completed. Both groups showed improvements in all MCCB domain scores, with no significant differences between the study groups (no interaction effect: F1,37 = 1.52, P = NS). Improvements in neurocognitive performance were significantly correlated with reductions in depression ratings posttreatment. The AMI-SF score was significantly lower (based on consistent answers from pre- to posttreatment) in the ECT group (72.9%) than in the APT group (80.8%, P = .025), indicating reduced consistency in autobiographical memory after ECT. CONCLUSIONS: General neurocognitive function was unaffected by RUL brief-pulse ECT treatment and positively related to improved mood in bipolar depression. Autobiographical memory consistency was reduced in patients treated with ECT. The results suggest that ECT can be used in treatment-resistant bipolar depression without compromising general neurocognitive function. The clinical relevance of reduced autobiographical memory consistency in the ECT group requires further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00664976.

Exercise capacity after extremely preterm birth. Development from adolescence to adulthood.

RATIONALE: Extremely preterm (EP) birth is associated with a series of adverse health outcomes, some of which may be alleviated by improved physical fitness. However, EP-born subjects are reportedly less physically active than term-born peers. Exercise capacity is poorly described in this group, and longitudinal data are needed. OBJECTIVES: To compare exercise capacity of adults born EP and at term, and to address developmental patterns from adolescence to adulthood. METHODS: An area-based cohort of adults, born in 1982-1985 at gestational age 28 weeks or earlier, or with birth weight of 1,000 g or less, originally examined at 18 years of age, were re-examined at 25 years of age together with individually matched term-born control subjects, using an identical maximal cardiopulmonary treadmill exercise test and validated questionnaires. MEASUREMENTS AND MAIN RESULTS: A total of 34 (76%) eligible preterm and 33 (85%) term control subjects successfully completed the exercise test at age 25 years. In the two groups, average (95% confidence interval) peak oxygen consumption was 40.7 (37.9-43.5) and 44.2 (41.0-47.4) ml ⋅ kg(-1)⋅min(-1), respectively, whereas the distance completed on the treadmill was 910 (827-993) m and 1,020 (927-1,113) m. Peak oxygen consumption was unrelated to neonatal factors and current FEV1, but was positively associated with leisure-time physical activity and negatively associated with age at examination. Values obtained at age 18 and 25 years were strongly correlated and within normal range at both examinations. CONCLUSIONS: Exercise capacity was modestly reduced in EP-born adults; however, values were within a normal range, positively associated with self-reported physical activity and unrelated to neonatal factors and current airway obstruction.

Ventricular dilatation in ex-prematures: only confined to the occipital region? MRI-based normative standards for 19-year-old ex-prematures without major handicaps.

BACKGROUND: Premature birth may be associated with white matter injury later developing with widening of the ventricles. However, population-based data on normal ventricular size by age are sparse, making the evaluation of possible ventricular dilatation difficult. PURPOSE: To present the linear measurements of the ventricular system, to compare these to subjectively assessed ventricular size, and to examine differences in ventricular size between ex-prematures and controls. MATERIAL AND METHODS: Eligible survivors (n = 113) from the initial birth cohort (n = 217, born in 1986-1988, birth weight <2000 g) underwent MRI during 2006-2007. One hundred and three were ex-premature and included in the study. The ventricular size was subjectively judged by a pediatric neuroradiologist, and scored as normal, mildly, moderately, or severely dilated. Objective measurements, including width and depth of the frontal and occipital horns, were performed in a blinded fashion, by a pediatric radiologist. RESULTS: The normative standards for different parts of the ventricular system in ex-premature young adults varied considerably. We found significant associations between the objective measurements and the subjectively classification of ventricular dilatation. Ex-prematures had smaller heads than those born term (control group). After adjustment for head circumference, there were no significant group differences regarding the frontal horns, but the occipital horns were proportionately wider among ex-prematures. CONCLUSION: Young adults born prematurely, with a birth weight <2000 g, do not have larger lateral ventricles than healthy controls born term, even after correcting for a smaller head size. However, they do have larger occipital horns, confirming previous studies and strengthening our belief of a specific vulnerability of the occipital region.

Patterns of local recurrence and dose fractionation of adjuvant radiation therapy in 462 patients with soft tissue sarcoma of extremity and trunk wall.

PURPOSE: To study the impact of dose fractionation of adjuvant radiation therapy (RT) on local recurrence (LR) and the relation of LR to radiation fields. METHODS AND MATERIALS: LR rates were analyzed in 462 adult patients with soft tissue sarcoma who underwent surgical excision and adjuvant RT at five Scandinavian sarcoma centers from 1998 to 2009. Medical records were reviewed for dose fractionation parameters and to determine the location of the LR relative to the radiation portals. RESULTS: Fifty-five of 462 patients developed a LR (11.9%). Negative prognostic factors included intralesional surgical margin (hazard ratio [HR]: 7.83, 95% confidence interval [CI]: 3.08-20.0), high malignancy grade (HR: 5.82, 95% CI: 1.31-25.8), age at diagnosis (HR per 10 years: 1.27, 95% CI: 1.03-1.56), and malignant peripheral nerve sheath tumor histological subtype (HR: 6.66, 95% CI: 2.56-17.3). RT dose was tailored to margin status. No correlation between RT dose and LR rate was found in multiple Cox regression analysis. The majority (65%) of LRs occurred within the primary RT volume. CONCLUSIONS: No significant dose-response effect of adjuvant RT was demonstrated. Interestingly, patients given 45-Gy accelerated RT (1.8 Gy twice daily/2.5 weeks) had the best local outcome. A total dose of 50 Gy in 25 fractions seemed adequate following wide margin surgery. The risk of LR was associated with histopathologic subtype, which should be included in the treatment algorithm of adjuvant RT in soft tissue sarcoma.

Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression.

BACKGROUND: The literature on the neuropsychological profiles in Bipolar disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning. METHODS: Acutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures. RESULTS: Neurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms. CONCLUSIONS: A high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant bipolar depression, particularly in BD I. TRIAL REGISTRATION: NCT00664976.

The effects of reducing the thermal index for bone from 1.0 to 0.5 and 0.1 on common obstetric pulsed wave Doppler measurements in the second half of pregnancy.

OBJECTIVE: To test the hypothesis that clinically relevant vessels can be visualized and interrogated with Doppler recording during the second half of pregnancy at an output energy below the currently advocated limits without loss of information. DESIGN: Observational cross-sectional study. SETTING: Tertiary fetal medicine center. SAMPLE: Based on a power calculation for equivalence studies, we recruited 65 pregnant women. METHODS: Ultrasound examination was performed at 18, 24 or 36 weeks of gestation. The umbilical artery, middle cerebral artery, ductus venosus, and both uterine arteries were identified using color Doppler, and the blood velocities were measured using pulsed wave Doppler at a thermal index for bone (TIB) of 1.0. This procedure was repeated at TIB values of 0.5 and 0.1. The depth of Doppler recording was noted. MAIN OUTCOME MEASURES: Visualization of the vessels by color Doppler at all power levels and any systematic changes or increased variance of the recorded parameters with decreasing power level. RESULTS: All vessels could be visualized by color Doppler and their flow velocities measured using pulsed wave Doppler in all participants and at all power levels. There were no systematic changes or increased parameter variance when reducing the power level, despite the insonation depth being significantly greater than in early pregnancy. CONCLUSIONS: Reducing the ultrasound power from TIB 1.0 to 0.1 does not alter color Doppler visualization or pulsed wave Doppler measurements in the second half of pregnancy. The lower power level can be recommended as a starting point for clinical examinations throughout pregnancy.

Chronic fatigue syndrome 5 years after giardiasis: differential diagnoses, characteristics and natural course.

BACKGROUND: A high prevalence of chronic fatigue has previously been reported following giardiasis after a large waterborne outbreak in Bergen, Norway in 2004. The aim of this study was to describe and evaluate differential diagnoses and natural course of fatigue five years after giardiasis among patients who reported chronic fatigue three years after the infection. METHODS: Patients who three years after Giardia infection met Chalder's criteria for chronic fatigue (n=347) in a questionnaire study among all patients who had laboratory confirmed giardiasis during the Bergen outbreak (n=1252) were invited to participate in this study five years after the infection (n=253). Structured interviews and clinical examination were performed by specialists in psychiatry, neurology and internal medicine/infectious diseases. Fukuda et al's 1994 criteria were used to diagnose chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF). Self-reported fatigue recorded with Chalder Fatigue Questionnaire three and five years after infection were compared. RESULTS: 53 patients were included. CFS was diagnosed in 41.5% (22/53) and ICF in 13.2% (7/53). Chronic fatigue caused by other aetiology was diagnosed in 24.5% (13/53); five of these patients had sleep apnoea/hypopnoea syndrome, six had depression and five anxiety disorder, and among these two had more than one diagnosis. Fatigue had resolved in 20.8% (11/53). Self-reported fatigue score in the cohort was significantly reduced at five years compared to three years (p<0.001). CONCLUSION: The study shows that Giardia duodenalis may induce CFS persisting as long as five years after the infection. Obstructive sleep apnoea/hypopnoea syndrome, depression and anxiety were important differential diagnoses, or possibly comorbidities, to post-infectious fatigue in this study. Improvement of chronic fatigue in the period from three to five years after giardiasis was found.