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Several disease related factors of pulmonary hypertension (PH) can negatively impact the nutritional status, leading to an increased risk of malnutrition. However, there are no studies on the best method for nutritional screening in PH patients. Therefore, the aim of this study was to determine the diagnostic accuracy of two screening tools: the Malnutrition Universal Screening Tool (MUST) and the Mini Nutritional Assessment Short‐Form (MNA‐SF). This cross‐sectional single center study included PH outpatients. Cut‐off values MUST ≥ 1 and MNA‐SF ≤ 11 were used for state of (risk of) malnutrition. The diagnostic criteria of the Global Leadership Initiative on Malnutrition (GLIM) were used as reference for diagnosing malnutrition. Diagnostic accuracy was determined by sensitivity, specificity, predictive positive value, negative predictive value, Cohen's Kappa‐ value (K) and area under the curve. Out of the 103 PH patients (age 67 years (SD 11.5), 66% female), 27% were malnourished according to the GLIM criteria. Both MUST and MNA‐SF had an insufficient sensitivity (60.7% [CI: 41%–97%] vs. 64.3% [CI: 44%–81%]). The MUST had a specificity of 100% [CI: 95%–100%], PPV 100% [CI:94%–100%] and NPV 87.2% [CI:79%–93%]. The specificity of the MNA‐SF was 81.3% [CI:70%–89%], PPV 56.3% [CI: 39%–73%] and NPV 85.9% [CI: 77%–93%]. The MUST had a higher K‐value 0.692 and AUC (0.804) compared to the K‐value 0.437 and AUC (0.728) of the MNA‐SF. This study indicated that both MUST and MNA‐SF are inaccurate to detect (risk of) malnutrition in PH outpatients. Future studies are needed to strive for a more sensitive screening tool.

BackgroundInsight into the causes of colorectal cancer (CRC) in adolescent and young adult (AYA) patients is limited. Without definitive information, patients often shape their own beliefs on the cause of their illness, developing causal attributions. This study aims to examine the causal attributions of CRC in AYA patients, compare these with middle-aged and older adults CRC patient groups and explore the association between causal attributions and psychological distress.MethodsTwo cross-sectional questionnaire studies were conducted among CRC survivors diagnosed between 1998 and 2007 using the population-based PROFILES registry. Three groups were defined by age at diagnosis: AYA (18–39 years; n = 67), middle-aged (40–70 years; n = 1993) and older adult survivors (70+ years; n = 1922). Causal attributions were assessed in a single free-text item from the Brief Illness Perception Questionnaire and psychological distress measured by the Hospital Anxiety and Depression Scale.ResultsAYA survivors most often attributed their CRC to heredity (36.4%), lifestyle (14.5%) and chance (10.9%). AYA survivors attributed their CRC to these causes more frequently than middle-aged and older adult CRC survivors. AYA survivors who attributed their CRC to causes out of their control (chance, heredity) showed significantly lower mean scores on anxiety (4.3 vs. 5.6; p < 0.01) compared to AYAs who reported causes within their control (lifestyle, stress). No significant difference was found for depression.ConclusionAYA patients with CRC may benefit from in-depth discussion about the lack of known (biological) causes and how this does not directly imply a lifestyle or stress cause.

Background Left atrial appendage occlusion (LAAO) may be a viable option for stroke prevention in patients with non-valvular atrial fibrillation and a contraindication for oral anticoagulation. No evidence evaluating the safety of this procedure in patients with a cardiac implantable electronic device (CIED) exists. The aim of this study was to evaluate whether CIED function is affected by LAAO and to explore LAAO procedural characteristics and complications in patients with a CIED. Methods This single-center cohort study included consecutive patients scheduled for percutaneous LAAO. Patients with a CIED prior to LAAO were selected and compared to the patients without CIED, concerning procedural characteristics and peri-procedural complications. In the group of patients with CIEDs, essential pacemaker integrity parameters were compared before and after the procedure to detect possible micro and macro lead displacements. Results Thirty-one patients with CIED were scheduled for LAAO (age 73.7 ± 5.4 years, 65% males, CHA 2 DS 2 -VASc 4.3 ± 1.5, and HAS-BLED 3.3 ± 1.0). The 245 patients without CIED were younger, and HAS-BLED-score was slightly lower (69.4 ± 8.2 years, p  < 0.001; 2.8 ± 1.0, p  = 0.022). Patients without CIED more frequently underwent LAAO combined with catheter ablation ( p  = 0.002). All other procedural characteristics were comparable between both groups. No visible lead displacement was observed on chest X-ray after LAAO. Additionally, no differences in impedance, threshold, or intracardiac sensing in various CIED lead locations were found prior versus post LAAO. Conclusion This study supports the feasibility and safety of LAAO in patients with a CIED.

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who undergo balloon pulmonary angioplasty (BPA), pretreatment with PH‐targeted medical therapy may be beneficial to improve clinical parameters and pulmonary hemodynamics. This study aims to describe clinical results of PH‐targeted therapy prior to BPA. All consecutive patients with CTEPH who underwent BPA treatment were selected from our CTEPH database. Medical treatment strategy, clinical parameters, and pulmonary hemodynamics at time of diagnosis and at the first BPA were analyzed. In total 92 CTEPH patients who started BPA treatment (64.1% women; 60.4 ± 14.1 years of age; 62.0% NYHA FC III/IV) were included. Most patients received dual oral PH‐targeted medical therapy (68.5%) prior to BPA. Between diagnosis and first BPA (median time 13.9 [7.5–30.7] months) significant improvements were observed in patients treated with PH‐targeted medical therapy for both clinical (6MWD: +28.2 m [5.1–51.3], log NTproBNP: −0.4 pg/ml [−0.8 to −0.1]) as well as pulmonary hemodynamic parameters (mPAP: −6.5 mmHg [−8.5 to −4.5], CO: +0.6 L/min [0.2–1.0] and PVR: −2.8 WU [−3.5 to −2.1]). The overall complication rate per BPA (out of a total of 441 procedures) was 15.0% for patients on monotherapy and 14.9% for those on dual/triple PH‐targeted medical therapy. No severe complications occurred. In conclusion, pretreatment with PH‐targeted medical therapy prior to BPA results in an improvement in clinical‐ and pulmonary hemodynamic parameters.

Patients with advanced Parkinson's disease often have rapid swings between mobility and immobility, and many respond unsatisfactorily to adjustments in pharmacological treatment. We assessed whether globus pallidus pars interna (GPi) deep brain stimulation (DBS) gives greater functional improvement than does subthalamic nucleus (STN) DBS. We recruited patients from five centres in the Netherlands who were aged 18 years or older, had idiopathic Parkinson's disease, and had, despite optimum pharmacological treatment, at least one of the following symptoms: severe response fluctuations, dyskinesias, painful dystonias, or bradykinesia. By use of a computer-generated randomisation sequence, we randomly assigned patients to receive either GPi DBS or STN DBS (1:1), applying a minimisation procedure according to drug use (levodopa equivalent dose <1000 mg vs ≥1000 mg) and treatment centre. Patients and study assessors (but not those who assessed adverse events) were masked to treatment allocation. We had two primary outcomes: functional health as measured by the weighted Academic Medical Center Linear Disability Scale (ALDS; weighted by time spent in the off phase and on phase) and a composite score for cognitive, mood, and behavioural effects up to 1 year after surgery. Secondary outcomes were symptom scales, activities of daily living scales, a quality-of-life questionnaire, the occurrence of adverse events, and drug use. We used the intention-to-treat principle for all analyses. This trial is registered with www.controlled-trials.com, number ISRCTN85542074. Between Feb 1, 2007, and March 29, 2011, we enrolled 128 patients, assigning 65 to GPi DBS and 63 to STN DBS. We found no statistically significant difference in either of our primary outcomes: mean change in weighted ALDS (3·0 [SD 14·5] in the GPi group vs 7·7 [23·2] in the STN group; p=0·28) and the number of patients with cognitive, mood, and behavioural side-effects (36 [58%] of 62 patients in the GPi group vs 35 [56%] of 63 patients in the STN group; p=0·94). Secondary outcomes showed larger improvements in off-drug phase in the STN group compared with the GPi group in the mean change in unified Parkinson's disease rating scale motor examination scores (20·3 [16·3] vs 11·4 [16·1]; p=0·03), the mean change in ALDS scores (20·3 [27·1] vs 11·8 [18·9]; p=0·04), and medication (mean levodopa equivalent drug reduction: 546 [SD 561] vs 208 [521]; p=0·01). We recorded no difference in the occurrence of adverse events between the two groups. Other secondary endpoints showed no difference between the groups. Although there was no difference in our primary outcomes, our findings suggest that STN could be the preferred target for DBS in patients with advanced Parkinson's disease. Stichting Internationaal Parkinson Fonds, Prinses Beatrix Fonds, and Parkinson Vereniging.

Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.

Objectives Independent internal and external validation of three previously published CT-based radiomics models to predict local tumor progression (LTP) after thermal ablation of colorectal liver metastases (CRLM). Materials and methods Patients with CRLM treated with thermal ablation were collected from two institutions to collect a new independent internal and external validation cohort. Ablation zones (AZ) were delineated on portal venous phase CT 2–8 weeks post-ablation. Radiomics features were extracted from the AZ and a 10 mm peri-ablational rim (PAR) of liver parenchyma around the AZ. Three previously published prediction models (clinical, radiomics, combined) were tested without retraining. LTP was defined as new tumor foci appearing next to the AZ up to 24 months post-ablation. Results The internal cohort included 39 patients with 68 CRLM and the external cohort 52 patients with 78 CRLM. 34/146 CRLM developed LTP after a median follow-up of 24 months (range 5–139). The median time to LTP was 8 months (range 2–22). The combined clinical-radiomics model yielded a c-statistic of 0.47 (95%CI 0.30–0.64) in the internal cohort and 0.50 (95%CI 0.38–0.62) in the external cohort, compared to 0.78 (95%CI 0.65–0.87) in the previously published original cohort. The radiomics model yielded c-statistics of 0.46 (95%CI 0.29–0.63) and 0.39 (95%CI 0.28–0.52), and the clinical model 0.51 (95%CI 0.34–0.68) and 0.51 (95%CI 0.39–0.63) in the internal and external cohort, respectively. Conclusion The previously published results for prediction of LTP after thermal ablation of CRLM using clinical and radiomics models were not reproducible in independent internal and external validation. Clinical relevance statement Local tumour progression after thermal ablation of CRLM cannot yet be predicted with the use of CT radiomics of the ablation zone and peri-ablational rim. These results underline the importance of validation of radiomics results to test for reproducibility in independent cohorts. Key Points • Previous research suggests CT radiomics models have the potential to predict local tumour progression after thermal ablation in colorectal liver metastases, but independent validation is lacking. • In internal and external validation, the previously published models were not able to predict local tumour progression after ablation. • Radiomics prediction models should be investigated in independent validation cohorts to check for reproducibility. Graphical Abstract

BackgroundLow back pain is one of the leading causes of disability worldwide. Exercise therapy is widely recommended to treat persistent non-specific low back pain. While evidence suggests exercise is, on average, moderately effective, there remains uncertainty about which individuals might benefit the most from exercise.MethodsIn parallel with a Cochrane review update, we requested individual participant data (IPD) from high-quality randomised clinical trials of adults with our two primary outcomes of interest, pain and functional limitations, and calculated global recovery. We compiled a master data set including baseline participant characteristics, exercise and comparison characteristics, and outcomes at short-term, moderate-term and long-term follow-up. We conducted descriptive analyses and one-stage IPD meta-analysis using multilevel mixed-effects regression of the overall treatment effect and prespecified potential treatment effect modifiers.ResultsWe received IPD for 27 trials (3514 participants). For studies included in this analysis, compared with no treatment/usual care, exercise therapy on average reduced pain (mean effect/100 (95% CI) −10.7 (−14.1 to –7.4)), a result compatible with a clinically important 20% smallest worthwhile effect. Exercise therapy reduced functional limitations with a clinically important 23% improvement (mean effect/100 (95% CI) −10.2 (−13.2 to –7.3)) at short-term follow-up. Not having heavy physical demands at work and medication use for low back pain were potential treatment effect modifiers—these were associated with superior exercise outcomes relative to non-exercise comparisons. Lower body mass index was also associated with better outcomes in exercise compared with no treatment/usual care. This study was limited by inconsistent availability and measurement of participant characteristics.ConclusionsThis study provides potentially useful information to help treat patients and design future studies of exercise interventions that are better matched to specific subgroups.Protocol publication https://doi.org/10.1186/2046-4053-1-64

Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.

The goal of this report is to summarize the current situation and discuss possible search strategies for charged scalars, in non-supersymmetric extensions of the Standard Model at the LHC. Such scalars appear in Multi-Higgs-Doublet models, in particular in the popular Two-Higgs-Doublet model, allowing for charged and additional neutral Higgs bosons. These models have the attractive property that electroweak precision observables are automatically in agreement with the Standard Model at the tree level. For the most popular version of this framework, Model II, a discovery of a charged Higgs boson remains challenging, since the parameter space is becoming very constrained, and the QCD background is very high. We also briefly comment on models with dark matter which constrain the corresponding charged scalars that occur in these models. The stakes of a possible discovery of an extended scalar sector are very high, and these searches should be pursued in all conceivable channels, at the LHC and at future colliders.