Association Between Vegetation Size And Outcome In The POET Trial.

BACKGROUND: Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared to continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis (IE). We aimed to analyze whether step-down oral therapy compared to continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients undergoing surgery before step-down oral therapy. METHODS: We included patients without presence of aortic root abscess at diagnosis from the POET study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy and the primary endpoint (composite of all-cause mortality, unplanned cardiac surgery, embolic event or relapse of positive blood cultures during follow-up). RESULTS: A total of 368 patients (age 68±12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared to patients with small vegetations (n=244) (65% vs 20%, p<0.001). During a median 1406 days of follow-up, 146 patients reached the primary endpoint. Large vegetations were not associated with the primary endpoint (HR 0.74 [95% CI 0.47-1.18], p=0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. CONCLUSION: Step-down oral therapy safe in the presence of a large vegetation at diagnosis and among patients undergoing early cardiac surgery.

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension.

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.

Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis.

OBJECTIVE: To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality. METHODS: In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia. RESULTS: Out of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment. CONCLUSION: Moderate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence.

OBJECTIVE: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort of adolescents. METHODS: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercise step test that allowed fitness (VO2 max ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. RESULTS: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomic status (standardized ß: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). CONCLUSION: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realized with more favorable body composition.

The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).

BACKGROUND: Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. METHODS: The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). RESULTS: Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008). CONCLUSION: Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02748811.

Impact of U.S. Oil and Natural Gas Emission Increases on Surface Ozone Is Most Pronounced in the Central United States.

Observations of volatile organic compounds (VOCs) from a surface sampling network and simulation results from the EMAC (ECHAM5/MESSy for Atmospheric Chemistry) model were analyzed to assess the impact of increased emissions of VOCs and nitrogen oxides from U.S. oil and natural gas (O&NG) sources on air quality. In the first step, the VOC observations were used to optimize the magnitude and distribution of atmospheric ethane and higher-alkane VOC emissions in the model inventory for the base year 2009. Observation-based increases of the emissions of VOCs and NOx stemming from U.S. oil and natural gas (O&NG) sources during 2009-2014 were then added to the model, and a set of sensitivity runs was conducted for assessing the influence of the increased emissions on summer surface ozone levels. For the year 2014, the added O&NG emissions are predicted to affect surface ozone across a large geographical scale in the United States. These emissions are responsible for an increased number of days when the averaged 8-h ozone values exceed 70 ppb, with the highest sensitivity being in the central and midwestern United States, where most of the O&NG growth has occurred. These findings demonstrate that O&NG emissions significantly affect the air quality across most of the United States, can regionally offset reductions of ozone precursor emissions made in other sectors, and can have a determining influence on a region's ability to meet National Ambient Air Quality Standard (NAAQS) obligations for ozone.

Soluble urokinase plasminogen activator receptor (suPAR) is lower in disease-free patients but cannot rule out incident disease in patients with suspected cancer.

BACKGROUND: Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer. METHODS: Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis. RESULTS: Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83). CONCLUSIONS: suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.

Integration of absolute cardiovascular disease risk assessment into routine blood cholesterol testing at pathology services.

BACKGROUND: Absolute cardiovascular disease (CVD) risk assessment is recommended for primary prevention of CVD, yet uptake in general practice is limited. Cholesterol requests at pathology services provide an opportunity to improve uptake by integrating absolute CVD risk assessment with this service. OBJECTIVE: This study aimed to assess the feasibility of such an additional service. METHODS: Two-hundred and ninety-nine patients (45-74 years) referred to pathology services for blood cholesterol had measurement of all variables required to determine absolute CVD risk according to Framingham calculator (blood pressure, age, sex, smoking and diabetes status via self-report). Data were recorded via computer-based application. The absolute risk score was communicated via the report sent to the referring medical practitioner as per usual practice. Evaluation questionnaires were completed immediately post visit and at 1-, 3- and 6-month follow-up via telephone (n = 262). RESULTS: Absolute CVD risk reports were issued for 90% of patients. Most patients (95%) reported that the length of time for the pathology service assessment was acceptable, and 91% that the self-directed computer-based application was easy to use. Seventy-eight per cent reported a preference for pathology services to conduct absolute CVD risk assessment. Only 2% preferred a medical practitioner. Of follow-up patients, 202 (75%) had a consultation with a medical practitioner, during which, aspects of CVD risk prevention were discussed (cholesterol and blood pressure 74% and 69% of the time, respectively). CONCLUSIONS: Measurement of absolute CVD risk in pathology services is feasible, highly acceptable among middle-to-older adults and may increase uptake of guideline-directed care in general practice.

Review of the accuracy of multi-parametric MRI prostate in detecting prostate cancer within a local reporting service.

INTRODUCTION: Multi-parametric magnetic resonance imaging of the prostate is crucial in detecting prostate cancer (CaP) and staging local disease. The Prostate Imaging Reporting and Data System (PIRADS) scoring system is used to assess and classify lesions and enables communication between clinicians and radiologists. This study aimed to assess the accuracy of PIRADSv2 in detecting CaP using histopathology specimens within our local service. METHODS: This retrospective study included 192 patients between September 2016 and May 2019. All had mpMRI prostate examinations prior to biopsy or prostatectomy. Lesions on MRI were assigned a PIRADS score and comparison made with histopathology results. Gleason score ≥7 was considered as clinically significant prostate cancer (csCaP). We calculated accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting all CaP and csCaP. RESULTS: In the PIRADS 3 group, 32% were Gleason 6 and 32% were Gleason 7 lesions. In the PIRADS 4 group, 37% were Gleason 6 and 41% were Gleason ≥7. For PIRADS 5 lesions, 32% were Gleason 6 and 68% were Gleason ≥7. For all CaP, sensitivity was 84.7%, specificity 54.6%, PPV 82.3% and NPV 58.8%. For csCaP Gleason ≥7, PIRADS cut-off ≥3 had sensitivity, specificity, PPV and NPV of 95.7%, 39.3%, 47.5% and 94.1%, respectively, and cut-off ≥4 had sensitivity, specificity, PPV and NPV of 84.3%, 53.3%, 50.9% and 85.5%. CONCLUSIONS: This study confirms PIRADS has high accuracy, sensitivity and NPV for detecting all CaP and csCaP. A high NPV may obviate need for biopsy in low-risk patients.

Association of brachial-cuff excess pressure with carotid intima-media thickness in Australian adults: a cross-sectional study.

OBJECTIVE: Reservoir pressure parameters [e.g. reservoir pressure (RP) and excess pressure (XSP)] measured using tonometry predict cardiovascular events beyond conventional risk factors. However, the operator dependency of tonometry impedes widespread use. An operator-independent cuff-based device can reasonably estimate the intra-aortic RP and XSP from brachial volumetric waveforms, but whether these estimates are clinically relevant to preclinical phenotypes of cardiovascular risk has not been investigated. METHODS: The RP and XSP were derived from brachial volumetric waveforms measured using cuff oscillometry (SphygmoCor XCEL) in 1691 mid-life adults from the CheckPoint study (a population-based cross-sectional study nested in the Longitudinal Study of Australian Children). Carotid intima--media thickness (carotid IMT, n = 1447) and carotid--femoral pulse wave velocity (PWV, n = 1632) were measured as preclinical phenotypes of cardiovascular risk. Confounders were conventional risk factors that were correlated with both exposures and outcomes or considered as physiologically important. RESULTS: There was a modest association between XSP and carotid IMT (ß = 0.76 µm, 95% CI, 0.25-1.26 partial R = 0.8%) after adjusting for age, sex, BMI, heart rate, smoking, diabetes, high-density lipoprotein cholesterol and mean arterial pressure. Neither RP nor XSP were associated with PWV in the similarly adjusted models (ß = -0.47 cm/s, 95% CI, -1.15 to 0.20, partial R = 0.2% for RP, and ß = 0.04 cm/s, 95% CI, -0.59 to 0.67, partial R = 0.01% for XSP). CONCLUSION: Cuff-based XSP associates with carotid IMT independent of conventional risk factors, including traditional BP, but the association was weak, indicating that further investigation is warranted to understand the clinical significance of reservoir pressure parameters.

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis.

BACKGROUND: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Added Predictor to Existing Preoperative Risk Assessments.

BACKGROUND: Risk assessment strategies, such as using the American Society of Anesthesiologists (ASA) physical status classification, attempt to identify surgical high-risk patients. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker reflecting overall systemic inflammation and immune activation, and it could potentially improve the identification of high-risk surgical patients. METHODS: We included patients acutely admitted to the emergency department who subsequently underwent surgery within 90 days of admission. Patients were stratified into low-risk or high-risk groups, according to ASA classification (ASAlow: ASA I-II; ASAhigh: ASA III-VI) and suPAR level, measured at admission (suPARhigh above and suPARlow below 5.5 ng/ml), respectively. Pre-specified complications were identified in national registries and electronic medical records. The association between ASA classification, suPAR level, CRP and the rate of postoperative complications was analyzed with logistic regression and Cox regression analyses, estimating odds ratios and hazard ratios (HRs). RESULTS: During 90-day follow-up from surgery, 31 (7.0%) patients died and 158 (35.6%) patients had postoperative complications. After adjusting for age, sex, and ASA classification, the HR for 90-day postoperative mortality was 2.5 (95% CI 1.6-4.0) for every doubling of suPAR level. suPAR was significantly better than CRP at predicting mortality and all complications (P = 0.0036 and P = 0.0041, respectively). Combining ASA classification and suPAR level significantly improved prediction of mortality and the occurrence of a postoperative complication within 90 days after surgery (P < 0.0001). CONCLUSION: Measuring suPAR levels in acutely admitted patients may aid in identifying high-risk patients and improve prediction of postoperative complications.

suPAR is associated with risk of future acute surgery and post-operative mortality in acutely admitted medical patients.

BACKGROUND: Acutely admitted medical patients are often fragile and in risk of future surgery. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is a predictor of readmission and mortality in the acute care setting. We aimed to investigate if suPAR also predicts acute surgery, which is associated with higher mortality than elective surgery, and if it predicts post-operative mortality. METHODS: A retrospective registry-based cohort study of 17,312 patients admitted to an acute medical unit in Denmark, from 18 November 2013 until 30 September 2015. The first admission with available suPAR was defined as the index admission, and patients were followed via national registries until 1 January 2016. The risk of acute surgery during the entire follow-up period as well as the 90-day post-operative mortality risk was modeled by Cox regression analyses adjusted for sex, age, C-reactive protein, and Charlson Comorbidity Index (Charlson Score). RESULTS: Acute surgery was carried out on 2404 patients (13.9%) after a median of 45 days (interquartile range 5-186) following the index admission. Patients receiving acute surgery had higher baseline suPAR compared with patients receiving elective- or no surgery (p < 0.0001). The hazard ratio (HR) for acute surgery was 1.50 (95% confidence interval (CI): 1.42-1.59) for every doubling of the suPAR level in the adjusted Cox regression analysis. Death within 90 days occurred in 439 (18.3%) patients receiving acute surgery, and the adjusted HR for post-operative mortality was 1.73 (95% CI: 1.52-1.95). DISCUSSION: Elevated levels of suPAR in acutely admitted medical patients were independently associated with increased risk of future acute surgery as well as with 90-day post-operative mortality. TRIAL REGISTRATION: This retrospective registry-based cohort study was approved by the Danish Health and Medicines authority (reference no. 3-3013-1061/1). All processing of personal data followed national guidelines, and the project was approved by the Danish Data Protection Agency (reference no. HVH-2014-018, 02767).

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer.

In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were registered on admission, and plasma concentrations of biomarkers were measured. The primary outcome was incident cancer within 1 year. Out of 197 patients included, 39 patients (19.8%) were diagnosed with cancer. Patients with cancer were significantly older and had a higher burden of comorbidities and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs investigated nor self-reported weight loss was associated with cancer. In this study, previous cancer, CRP and suPAR were significantly associated with cancer diagnosis in patients with NSSC. Ficolin-1-3, MBL and pentraxin-3 were not associated with cancer.

Frailty and polypharmacy in elderly patients are associated with a high readmission risk.

INTRODUCTION: Many acutely ill elderly people are frail and suffer from polypharmacy. They often present with nonspecific symptoms at hospital admission and are therefore often under-triaged and insufficiently treated resulting in adverse health outcomes. This study aimed to investigate the prevalence of polypharmacy and frailty and to identify if frailty and polypharmacy may predict adverse health outcomes in elderly patients who are acutely admitted to hospital. METHODS: The study was a descriptive cohort study including patients ≥ 65 years acutely admitted to hospital during a 14-day period, n = 250. The included patients were assessed for frailty, and the total number of health problems requiring treatment, geriatric problems and medication were registered. RESULTS: Frail patients suffering from polypharmacy had significantly more health problems, 13-fold longer hospital stays, they were more often discharged to nursing homes and had a five times greater risk of readmission than patients without frailty and polypharmacy. Polypharmacy was present in 62% and hyper-polypharmacy in 20% of the patients, and frailty was present in 85% of the patients with polypharmacy and in 40% of those without polypharmacy. CONCLUSION: Compared with non-frail patients without polypharmacy, frail elderly patients with polypharmacy belong to a high-risk group and should receive an immediate geriatric assessment and treatment including long-term planning by the Mobile Geriatric Team. FUNDING: none. TRIAL REGISTRATION: The study was approved and registered with the Danish Data Protection Agency under the Capital Region of Denmark's joint notification of health research (j. no.: 2007-58-0015, AMH-2013-003, I-Suite no: 02495).

Aortic reservoir pressure corresponds to cyclic changes in aortic volume: physiological validation in humans.

OBJECTIVE: Aortic reservoir pressure indices independently predict cardiovascular events and mortality. Despite this, there has never been a study in humans to determine whether the theoretical principles of the mathematically derived aortic reservoir pressure (RP(derived)) and excess pressure (XP(derived)) model have a real physiological basis. This study aimed to directly measure the aortic reservoir (AR(direct); by cyclic change in aortic volume) and determine its relationship with RP(derived), XP(derived), and aortic blood pressure (BP). APPROACH AND RESULTS: Ascending aortic BP and Doppler flow velocity were recorded via intra-arterial wire in 10 men (aged 62 ± 12 years) during coronary artery bypass surgery. Simultaneous ascending aortic transesophageal echocardiography was used to measure AR(direct). Published mathematical formulae were used to determine RP(derived) and XP(derived). AR(direct) was strongly and linearly related to RP(derived) during systole (r=0.988; P<0.001) and diastole (r=0.985; P<0.001). Peak cross-correlation (r=0.98) occurred at a phase lag of 0.004 s into the cardiac cycle, suggesting close temporal agreement between waveforms. The relationship between aortic BP and AR(direct) was qualitatively similar to the cyclic relationship between aortic BP and RP(derived), with peak cross-correlations occurring at identical phase lags (AR(direct) versus aortic BP, r=0.96 at 0.06 s; RP(derived) versus aortic BP, r=0.98 at 0.06 s). CONCLUSIONS: RP(derived) is highly correlated with changes in proximal aortic volume, consistent with its physiological interpretation as corresponding to the instantaneous volume of blood stored in the aorta. Thus, aortic reservoir pressure should be considered in the interpretation of the central BP waveform.

Safe laparoscopic colorectal surgery performed by trainees.

OBJECTIVES: Laparoscopic surgery for colorectal cancer is safe, but there have been hesitations to implement the technique in all departments. One of the reasons for this may be suboptimal learning possibilities since supervised trainees have not been allowed to do the operations to an adequate extent for the technique to spread. We routinely plan all operations as laparoscopic procedures and most cases are done by supervised trainees. The present study therefore presents the results of operations performed by trainees compared with results obtained by experienced laparoscopic surgeons. DESIGN: Data for all patients who underwent elective colorectal cancer surgery in 2009 were recorded. Surgeries performed by laparoscopic inexperienced surgeons were compared with the outcome of surgery performed by laparoscopic experienced surgeons. These results were also compared with nationwide data extracted from the national database. SETTING: A university teaching department of surgery. PARTICIPANTS: A total of 131 patients underwent colorectal elective surgery in 2009 in the department. RESULTS: Of the 131 operations, 60% were performed by trainees supervised by experienced laparoscopic colorectal surgeons. The trainees performed a total of 70% of all colonic procedures and 43% of all rectal resections. There were no statistically significant differences between the inexperienced and experienced laparoscopic surgeons with regards to short-term outcome other than increased duration of surgery for colonic resections (198 vs 140 min, p = 0.005). Thus, we found no difference regarding length of stay, conversion to laparotomy, intraoperative bleeding or complications, postoperative complications, or 30-day mortality. CONCLUSIONS: Our data suggest that laparoscopic surgery for colorectal cancer can be performed safely by supervised trainees with good short term results. Therefore, a high volume of operations with an educational potential can easily be maintained when going from open to laparoscopic surgery as the standard operative technique for colorectal cancer in a university department of surgery.

Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study.

New treatments are required for rituximab-refractory follicular lymphoma (FL). In the present study, patients with rituximab-refractory FL received 8 weekly infusions of ofatumumab (CD20 mAb; dose 1, 300 mg and doses 2-8, 500 or 1000 mg; N = 116). The median age of these patients was 61 years, 47% had high-risk Follicular Lymphoma International Prognostic Index scores, 65% were chemotherapy-refractory, and the median number of prior therapies was 4. The overall response rate was 13% and 10% for the 500-mg and 1000-mg arms, respectively. Among 27 patients refractory to rituximab monotherapy, the overall response rate was 22%. The median progression-free survival was 5.8 months. Forty-six percent of patients demonstrated tumor reduction 3 months after therapy initiation, and the median progression-free survival for these patients was 9.1 months. The most common adverse events included infections, rash, urticaria, fatigue, and pruritus. Three patients experienced grade 3 infusion-related reactions, none of which were considered serious events. Grade 3-4 neutropenia, leukopenia, anemia, and thrombocytopenia occurred in a subset of patients. Ofatumumab was well tolerated and modestly active in this heavily pretreated, rituximab-refractory population and is therefore now being studied in less refractory FL and in combination with other agents in various B-cell neoplasms. The present study was registered at www.clinicaltrials.gov as NCT00394836.