Automatic detection of actionable findings and communication mentions in radiology reports using natural language processing

__Objectives:__ To develop and validate classifiers for automatic detection of actionable findings and documentation of nonroutine communication in routinely delivered radiology reports. __Me

Assessment of actionable findings in radiology reports

Purpose: The American College of Radiology (ACR) Actionable Reporting Work Group defined three categories of imaging findings that require additional, nonroutine communication wit

Unresectable Intermediate-Size (3–5 cm) Colorectal Liver Metastases:Stereotactic Ablative Body Radiotherapy Versus Microwave Ablation (COLLISION-XL): Protocol of a Phase II/III Multicentre Randomized Controlled Trial

Background: Although microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3–5 cm) CRLM. Methods: In this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1–3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life. Discussion: Current guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3–5 cm. Level of Evidence : Level 1, phase II/ III Randomized controlled trial. Trial Registration: NCT04081168, September 9th 2019. Graphical Abstract: [Figure not available: see fulltext.]</p

Unresectable Intermediate-Size (3–5 cm) Colorectal Liver Metastases:Stereotactic Ablative Body Radiotherapy Versus Microwave Ablation (COLLISION-XL): Protocol of a Phase II/III Multicentre Randomized Controlled Trial

Background: Although microwave ablation (MWA) has a low complication rate and good efficacy for small-size (≤ 3 cm) colorectal liver metastases (CRLM), local control decreases with increasing size. Stereotactic body radiotherapy (SBRT) is gaining interest as a potential means to treat intermediate-size CRLM and might be less susceptible to increasing volume. The objective of this study is to compare the efficacy of MWA to SBRT in patients with unresectable, intermediate-size (3–5 cm) CRLM. Methods: In this two-arm, multicentre phase II/ III randomized controlled trial, 68 patients with 1–3 unresectable, intermediate-size CRLM suitable for both MWA and SBRT, will be included. Patients will be treated with MWA or SBRT as randomised. The Primary endpoint is local tumour progression-free survival (LTPFS) at 1 year (intention-to-treat analysis). Main secondary endpoints are overall survival, overall and distant progression-free survival (DPFS), local control (LC) and procedural morbidity and mortality and assessment of pain and quality of life. Discussion: Current guidelines lack clear recommendations for the local treatment of liver only intermediate-size, unresectable CRLM and studies comparing curative intent SBRT and thermal ablation are scarce. Although safety and feasibility to eradicate tumours ≤ 5 cm have been established, both techniques suffer from lower LTPFS and LC rates for larger-size tumours. For the treatment of unresectable intermediate-size CRLM clinical equipoise has been reached. We have designed a two-armed phase II/ III randomized controlled trial directly comparing SBRT to MWA for unresectable CRLM 3–5 cm. Level of Evidence : Level 1, phase II/ III Randomized controlled trial. Trial Registration: NCT04081168, September 9th 2019. Graphical Abstract: [Figure not available: see fulltext.]</p

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: An open-label single-center study

Abstract. Background: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. Methods. Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (-1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness.Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (man

Molecular assessment of bacterial vaginosis by Lactobacillus abundance and species diversity

__Background:__ To date, women are most often diagnosed with bacterial vaginosis (BV) using microscopy based Nugent scoring or Amsel criteria. However, the accuracy is less than optimal. The aim of the present study was to confirm the identity of known BV-associated composition profiles and evaluate indicators for BV using three molecular methods. __Methods:__ Evaluation of indicators for BV was carried out by 16S rRNA amplicon sequencing of the V5-V7 region, a tailor-made 16S rRNA oligonucleotide-based microarray, and a PCR-based profiling technique termed IS-profiling, which is based on fragment variability of the 16S-23S rRNA intergenic spacer region. An inventory of vaginal bacterial species was obtained from 40 females attending a Dutch sexually transmitted infection outpatient clinic, of which 20 diagnosed with BV (Nugent score 7-10), and 20 BV negative (Nugent score 0-3). __Results:__ Analysis of the bacterial communities by 16S rRNA amplicon sequencing revealed two clusters in the BV negative women, dominated by either Lactobacillus iners or Lactobacillus crispatus and three distinct clusters in the BV positive women. In the former, there was a virtually complete, negative correlation between L. crispatus and L. iners. BV positive subjects showed cluster profiles that were relatively high in bacterial species diversity and dominated by anaerobic species, including Gardnerella vaginalis, an

Lipid-mediated Wnt protein stabilization enables serum-free culture of human organ stem cells

Wnt signalling proteins are essential for culture of human organ stem cells in organoids, but most Wnt protein formulations are poorly active in serum-free media. Here we show that purified Wnt3a protein is ineffective because it rapidly loses activity in culture media due to its hydrophobic nature, and its solubilization requires a detergent, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propanesulfonate), that interferes with stem cell self-renewal. By stabilizing the Wnt3a protein using phospholipids and cholesterol as carriers, we address both problems: Wnt activity remains stable in serum-free media, while non-toxic carriers allow the use of high Wnt concentrations. Stabilized Wnt3a supports strongly increased self-renewal of organ and embryonic stem cells and the serum-free establishment of human organoids from healthy and diseased intestine and liver. Moreover, the lipophilicity of Wnt3a protein greatly facilitates its purification. Our findings remove a major obstacle impeding clinical applications of adult stem cells and offer advantages for all cell culture uses of Wnt3a protein

Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas. Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME. Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas ( < 3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas. Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas

Five-year outcomes of chronic total occlusion treatment with a biolimus A9-eluting biodegradable polymer stent versus a sirolimus-eluting permanent polymer stent in the LEADERS all-comers trial

Background: Few data are available on long-term follow-up of drug-eluting stents in the treatment of chronic total occlusion (CTO). The LEADERS CTO sub-study compared the long-term results in CTO and non-CTO lesions of a Biolimus A9™-eluting stent (BES) with a sirolimus-eluting stent (SES). Methods: Among 1,707 patients enrolled in the prospective, multi-center, all-comers LEADERS trial, 81 with CTOs were treated with either a BES (n = 45) or a SES (n = 36). The primary endpoint was the occurrence of major adverse cardiac events (MACE): cardiac death, myocardial infarction (MI) and clinically-indicated target vessel revascularization (TVR). Results: At 5 years, the rate of MACE was numerically higher in the CTO group than in the non-CTO group (29.6% vs. 23.3%; p = 0.173), with a significant increase in the incidence of target lesion revascularization (TLR) (21.0 vs. 12.6; p = 0.033), but no difference in stent thrombosis (ST). Patients with CTO receiving a BES demonstrated a lower incidence of MACE (22.2% vs. 38.9%; p = 0.147) with a significant reduction in TLR compared to patients receiving a SES (11.1% vs. 33.3%, p = 0.0214) with an incidence similar to that observed in the non-CTO group treated with BES (11.6%). Definite ST at 5 years nearly halved in the BES group (4.4% vs. 8.3%, p = 0.478) with no ST in the BES group after the first year (0% vs. 8.3%, p for interaction = 0.009). Conclusions: The use of a BES showed a reduction in MACE, TVR, TLR, and ST over time in the CTO subset with similar outcome as for non-CTO lesions

Clinical features and predictors for disease natural progression in adults with Pompe disease: A nationwide prospective observational study

Background: Due partly to physicians' unawareness, many adults with Pompe disease are diagnosed with great delay. Besides, it is not well known which factors influence the rate of disease progression, and thus disease outcome. We delineated the specific clinical features of Pompe disease in adults, and mapped out the distribution and severity of muscle weakness, and the sequence of involvement of the individual muscle groups. Furthermore, we defined the natural disease course and identified prognostic factors for disease progression. Methods. We conducted a single-center, prospective, observational study. Muscle strength (manual muscle testing, and hand-held dynamometry), muscle function (quick motor function test), and pulmonary function (forced vital capacity in sitting and supine positions) were assessed every 3-6 months and analyzed using repeated-measures ANOVA. Results: Between October 2004 and August 2009, 94 patients aged between 25 and 75 years were includ