Bilirubin isomers during LED phototherapy of hyperbilirubinemic neonates, blue-green (~478 nm) vs blue.

BACKGROUND: The clinical part of this randomized controlled trial concerning phototherapy of neonates with hyperbilirubinemia showed that the recommended blue-green LED light (≈478 nm) was 31% more efficient than standard blue LED light (≈459 nm) measured by the decline in total serum bilirubin. Lumirubin has biologic effects. The aim was to compare the serum bilirubin isomers, efficacy, and biologic effects between the two phototherapy groups. METHODS: Inclusion criteria: neonates healthy except for hyperbilirubinemia, gestational age ≥33 weeks, birth weight ≥1800 g, and postnatal age >24 h. Forty-two neonates were randomized to receive overhead blue-green light and 44 blue light. Treatment 24 h. The light irradiance was equal. RESULTS: The percentage decrease of combined bilirubin isomers was 47.8% for blue-green light vs 33.4% for blue light, the ratio being 1.43. Corresponding values for Z,Z-bilirubin were 55.6% vs 44.2%, the ratio being 1.26. The increase in the absolute serum concentrations of the photoisomer Z,E-bilirubin and thereby combined photoisomers were greater using blue light. CONCLUSION: Blue-green light was essentially more efficient determined by the decline of combined bilirubin isomers and Z,Z-bilirubin itself. Regarding biological effects neonates receiving blue-green light might be more affected than neonates receiving blue light. IMPACT: Phototherapy of hyperbilirubinemic neonates using blue-green LED light with a peak emission of 478 nm was 43% more efficient than standard blue LED light with a peak emission of 459 nm was measured by the decline of serum combined bilirubin isomers, and the decline of toxic Z,Z-bilirubin was 26% greater. Apparently, there was a discrepancy between the huge drop in total serum bilirubin and the low serum concentrations of E,Z-bilirubin and E,Z-lumirubin. This was caused by the rapid excretion of E,Z-lumirubin. Lumirubin has biologic effects. Due to greater lumirubin production neonates exposed to blue-green light might be more affected than those exposed to blue light.

Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study.

BACKGROUND: Colorectal cancer (CRC) is often diagnosed in advanced stages. Circulating tumour DNA (ctDNA) has been proposed as an early diagnostic biomarker. However, as a screening tool, ctDNA has mainly been studied in selected populations at the time of clinical diagnosis. The aim of this study was to detect CRC by known ctDNA markers up to 2 years prior to clinical diagnosis. METHODS: In this case-control study, methylated ctDNA markers were detected in plasma samples from 106 healthy controls and 106 individuals diagnosed with CRC within 24 months following participation in The Trøndelag Health Study. RESULTS: The most specific single markers were BMP3, FLI1, IKZF1, SFRP1, SFRP2, NPTX2, SLC8A1 and VIM (specificity >70%). When combining these into a panel, the CRC sensitivity was 43% (95% CI 42.7-43.4) and the CRC specificity was 86% (95% CI 85.7-86.2). The findings were reproduced in an independent validation set of samples. CONCLUSIONS: Detection of known methylated ctDNA markers of CRC is possible up to 2 years prior to the clinical diagnosis in an unselected population resembling the screening setting. This study supports the hypothesis that some patients could be diagnosed earlier, if ctDNA detection was part of the CRC screening programme.

Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with stage III or IV pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma remains one of the major causes of cancer-related mortality globally. Unfortunately, current prognostic biomarkers are limited, and no predictive biomarkers exist. This study examined promoter hypermethylation of secreted frizzled-related protein 1 (phSFRP1) in cfDNA as a prognostic biomarker and predictor of treatment effect in patients with metastatic FOLFIRINOX-treated PDAC and locally advanced PDAC. METHODS: We performed methylation-specific PCR of the SFRP1 genes' promoter region, based on bisulfite treatment. Survival was assessed as time-to-event data using the pseudo-observation method and analyzed with Kaplan-Meier curves and generalized linear regressions. RESULTS: The study included 52 patients with FOLFIRINOX-treated metastatic PDAC. Patients with unmethylated (um) SFRP1 (n = 29) had a longer median overall survival (15.7 months) than those with phSFRP1 (6.8 months). In crude regression, phSFRP1 was associated with an increased risk of death of 36.9% (95% CI 12.0%-61.7%) and 19.8% (95% CI 1.9-37.6) at 12 and 24-months, respectively. In supplementary regression analysis, interaction terms between SFRP1 methylation status and treatment were significant, indicating reduced benefit of chemotherapy. Forty-four patients with locally advanced PDAC were included. phSFRP1 was associated with an increased risk of death at 24-months CONCLUSIONS: This indicates that phSFRP1 is a clinically useful prognostic biomarker in metastatic PDAC and possibly in locally advanced PDAC. Together with existing literature, results could indicate the value of cfDNA-measured phSFRP1 as a predictive biomarker of standard palliative chemotherapy in patients with metastatic PDAC. This could facilitate personalized treatment of patients with metastatic PDAC.

A simplified HPLC-based method for measuring unconjugated bilirubin, bilirubin-monoglucuronide, bilirubin-diglucuronide, and delta-bilirubin in plasma with increased conjugated bilirubin.

Prolonged icterus is an important and common problem in neonatology and accurate determination of the different bilirubin species, including differentiation between delta-bilirubin and mono- and di-conjugated bilirubin, is useful for diagnostic purposes. However, most bilirubin measurements routinely performed in the clinical laboratory are hampered by the lack of separation of the four bilirubin fractions (unconjugated bilirubin, mono-conjugated bilirubin, di-conjugated bilirubin, and delta-bilirubin). Herein, we propose a high-performance liquid chromatography-based method, independent of commercially available standards or reliable molar absorption coefficients, for the determination of bilirubin fractions in blood samples from icteric patients. The method is a robust and reliable candidate for a semi-automatized setup for measuring the various bilirubin fractions in a specialized laboratory handling samples from clinics with expertise in biliary disease.

Early Laboratory Diagnosis of COVID-19 by Antigen Detection in Blood Samples of the SARS-CoV-2 Nucleocapsid Protein.

The purpose of this study was to characterize the diagnostic performance of a newly developed enzyme-linked immunosorbent assay (ELISA) for detection of SARS-CoV-2 nucleocapsid protein (NP) in blood. Blood samples were collected during hospitalization of 165 inpatients with PCR-confirmed SARS-CoV-2 infection and from 505 outpatients predominantly with relevant symptoms of COVID-19 simultaneously with PCR testing. For the 143 inpatients who had their first blood sample collected within 2 weeks after PCR-confirmed infection, the diagnostic sensitivity of the ELISA was 91.6%. The mean NP concentration of the 131 ELISA-positive blood samples was 1,734 pg/ml (range, 10 to 3,840 pg/ml). An exponential decline in NP concentration was observed for 368 blood samples collected over the first 4 weeks after PCR-confirmed SARS-CoV-2 infection, and all blood samples taken later had an NP concentration below the 10-pg/ml diagnostic cutoff. The diagnostic sensitivity of the ELISA was 81.4% for the 43 blood samples collected from outpatients with a simultaneous positive PCR test, and the mean NP concentration of the 35 ELISA-positive samples was 157 pg/ml (range, 10 to 1,377 pg/ml). For the 462 outpatients with a simultaneous negative PCR test, the diagnostic specificity of the ELISA was 99.8%. In conclusion, the SARS-CoV-2 NP ELISA is a suitable laboratory diagnostic test for COVID-19, particularly for hospitals, where blood samples are readily available and screening of serum or plasma by ELISA can facilitate prevention of nosocomial infections and reduce the requirement for laborious swab sampling and subsequent PCR analysis to confirmatory tests only.

Cell-free DNA promoter hypermethylation as a diagnostic marker for pancreatic ductal adenocarcinoma - An external validation study.

BACKGROUND: We recently identified a diagnostic prediction model based on promoter hypermethylation of eight selected genes in plasma cell-free (cf) DNA, which showed promising results as a diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to validate this biomarker profile in an external patient cohort and examine any additional effect of serum CA 19-9. METHODS: Patients with PDAC (n = 346, stage I-IV) and chronic pancreatitis (n = 25) were included. Methylation-specific PCR of a 28-gene panel was performed on serum cfDNA samples. The previously developed diagnostic prediction model (age>65 years, BMP3, RASSF1A, BNC1, MESTv2, TFPI2, APC, SFRP1 and SFRP2) was validated alone and in combination with serum CA 19-9 in this external patient cohort. RESULTS: Patients with PDAC had a higher number of hypermethylated genes (mean 8.11, 95% CI 7.70-8.52) than patients with chronic pancreatitis (mean 5.60, 95% CI 4.42-6.78, p = 0.011). Validation of the diagnostic prediction model yielded an AUC of 0.77 (95% CI 0.69-0.84). The combination of serum CA 19-9 and our test had an AUC of 0.93 (95% CI 0.89-0.96) in the primary study and 0.85 (95% CI 0.79-0.91) in the validation study. CONCLUSION: In this validation study, PDAC was associated with a higher number of hypermethylated genes in serum cfDNA than chronic pancreatitis. Our diagnostic test was superior to the predictive value of serum CA 19-9 alone in both the primary and the validation study. The combination of our test with CA 19-9 may serve as a clinically useful diagnostic biomarker for PDAC.

Concurrent musculoskeletal complaints in elbows, shoulders, and necks after common hand and forearm injuries or conditions: A cross-sectional study among 600 patients.

STUDY DESIGN: This is a cross-sectional study among 600 patients. INTRODUCTION: Isolated hand and forearm injuries or conditions are common in the emergency and orthopedic departments. So far, little is known about whether these patients suffer from concurrent musculoskeletal complaints (MSCs) besides their hand and forearm complaints. Neglecting concurrent MSCs in the upper limbs and necks could hamper rehabilitation and prolong the time taken to return to daily and work-related activities. PURPOSE OF THE STUDY: The purpose of this study was to investigate the prevalence of concurrent MSCs in the elbow, shoulder, and neck after common hand and/or forearm injuries or conditions. METHODS: This study included 600 patients with any type of diagnosis referred to rehabilitation after hand and/or forearm injuries or conditions. Basic characteristics, diagnoses, and location of patients' symptoms were collected and analyzed. RESULTS: The overall prevalence of concurrent MSCs was 40%. Twenty-eight percent of the whole sample developed concurrent MSCs after the hand and forearm injury or condition. The gender distribution was 68% women and 32% men. The most common location for complaints was the shoulder (62%), followed by the elbow (49%), and the neck (32%). DISCUSSION: The present results suggest that MSCs from the elbows, shoulders, or necks are very common in patients with hand and/or forearm injuries or conditions. CONCLUSION: Clinicians treating patients with isolated hand and forearm injuries or conditions should be aware of the high prevalence of concurrent MSCs. Future research should investigate if specific rehabilitation, focusing on concurrent MSCs, may influence the outcome in this population.

Promoter hypermethylation in plasma-derived cell-free DNA as a prognostic marker for pancreatic adenocarcinoma staging.

Correct staging of pancreatic cancer is paramount, as treatment is stage specific. However, minimally invasive tools to facilitate staging are lacking. DNA promoter hypermethylation is a hallmark of cancer. The aim of this study is to evaluate promoter hypermethylation in cell-free DNA as a prognostic marker for stage classification of pancreatic adenocarcinoma. Consecutive patients with pancreatic adenocarcinoma were prospectively included. Plasma samples were obtained before diagnostic work-up and treatment. Patients were staged according to the TNM classification. Methylation-specific PCR of 28 genes was performed. Prognostic prediction models for staging of pancreatic adenocarcinoma were developed by multivariable logistic regression analysis using stepwise backwards elimination. Ninety-five patients with pancreatic adenocarcinoma were included. The mean number of hypermethylated genes was identical for stage I, II and III disease (7.09 (95% CI; 5.51-8.66), 7.00 (95% CI; 5.93-8.07) and 6.77 (95% CI; 5.08-8.46)), respectively, and highly significantly different from stage IV disease (10.24 (95% CI; 8.88-11.60)). The prediction model (SEPT9v2, SST, ALX4, CDKN2B, HIC1, MLH1, NEUROG1, and BNC1) enabled the differentiation of stage IV from stage I-III disease (AUC of 0.87 (cut point 0.55; sensitivity 74%, specificity 87%)). Model (MLH1, SEPT9v2, BNC1, ALX4, CDKN2B, NEUROG1, WNT5A, and TFPI2) enabled the differentiation of stage I-II from stage III-IV disease (AUC of 0.82 (cut point 0.66; sensitivity 73%, specificity 80%)). Cell-free DNA promoter hypermethylation has the potential to be blood-based prognostic markers for pancreatic adenocarcinoma, as panels of hypermethylated genes enables the differentiation according to cancer stage. However, further validation is required.

Symptomatology, Clinical Presentation and Basic Work up in Patients with Suspected Pulmonary Embolism.

Basic knowledge of pulmonary embolism is relevant to most practicing physicians. Many medical specialties care for patients with increased risk of pulmonary embolism, why recognition of relevant symptoms, a thorough medical history, assessment of the clinical condition of the patient and possibly referral to a relevant facility should be a part of the skills of all clinicians. Sudden onset dyspnea, chest pain, syncope and hemoptysis are essential symptoms of pulmonary embolism, and in most of these patients basic investigations like arterial blood gas analysis, electrocardiogram, chest x-ray and biochemical analyses are appropriate. In addition, lung ultrasound and echocardiography are indicated in many of these patients. The information available from the medical history, clinical assessment and basic investigation form the basis on which the decision about further diagnostic imaging and intensity of treatment and monitoring can be made. These decisions can be guided by clinical scoring systems like the Wells score, revised Geneva score and the PESI.

Radionuclide Diagnosis of Pulmonary Embolism.

Diagnostic imaging plays an integral role in the diagnostic workup of suspected pulmonary embolism, and several modalities have been employed over the years. In recent years, the choice has been narrowed to either computer tomographic or radionuclide based methods, i.e. computer tomographic angiography (CTA) and ventilation-perfusion scintigraphy (V/Q-scan). Both methods display advantages and shortcomings, and while we provide some insights into CTA and alternative methods, the paper's main focus is a review of the V/Q-scan. We discuss basic considerations, interpretation criteria, clinical value, and controversies of conventional planar lung scintigraphy as well as the more contemporary 3-dimensional imaging technique of single photon emission tomography (SPECT) with or without CT.

State-of-the-Art Imaging in Pulmonary Embolism: Ventilation/Perfusion Single-Photon Emission Computed Tomography versus Computed Tomography Angiography - Controversies, Results, and Recommendations from a Systematic Review.

Pulmonary embolism (PE) is a common, ubiquitous, and potentially lethal disease. As symptoms and clinical findings are notoriously nonspecific, diagnostic imaging is essential to avoid undertreatment as well as overtreatment. Controversies remain regarding first-line imaging in suspected PE. The two main contemporary contenders are ventilation/perfusion scintigraphy with single-photon emission computed tomography (V/Q SPECT) with or without additional low-dose CT (SPECT/CT) and CT angiography (CTA). We present our results from a systematic review and meta-analysis of the diagnostic performances of these modalities: V/Q SPECT, V/Q SPECT/CT, and CTA are all viable options, but we consider V/Q SPECT/CT to be superior in most clinical settings with better overall diagnostic performance, that is, pooled sensitivities (97.6 vs. 82.0%), specificities (95.9 vs. 94.9%), positive predictive values (93.0 vs. 93.8%), negative predictive values (98.6 vs. 84.7%), and accuracies (96.5 vs. 88.6%). We further address some of the ongoing controversies regarding the various modalities, that is, radiation exposure, the issues of subsegmental PE, nondiagnostic studies, and various challenges in specific patient populations.

Clinical utility of F-18 FDG PET-CT in the initial evaluation of lung cancer.

PURPOSE: Positron emission tomography-computed tomography (PET-CT) is a resource-demanding imaging modality with increasing popularity in the workup of patients with suspected or proven lung cancer. METHODS: To review the clinical usefulness of this imaging modality in the diagnosis, staging, and pre-operative evaluation, we conducted a systematic literature search, review, and quality assessment using the rapid evidence assessment toolkit and the Oxford Centre for Evidence-Based Medicine methodology. The literature search resulted in 4,208 records including 918 reviews, of which 139 met the predefined criteria and were read in full to identify relevant original articles on F-18 FDG PET-CT (1) in the evaluation of solitary pulmonary nodules (n = 14), (2) in curative-intent treatment trials (n = 9), and (3) in planning of invasive procedures (n = 18). RESULTS: We found the following important results from the literature review: 1) PET-CT can rule out malignancy in most solitary pulmonary nodules due to high sensitivity (recommendation level A). 2) PET-CT reduces the number of futile treatment trials (recommendation level A). 3) The sensitivity of PET-CT in general is insufficient to rule out mediastinal lymph node metastasis (recommendation level A). CONCLUSIONS: ᅟ 1) With few exceptions, solitary pulmonary nodules can safely be considered benign if the PET-CT scan is negative. Exceptions consist of small (<1 cm) and non-solid, solitary pulmonary nodules. These abnormalities should be followed up by CT in a structured programme. 2) No curative-intent treatment should be commenced until a PET-CT scan has excluded occult distant metastases. 3) In general, lymph node metastasis in the mediastinum cannot be ruled out on the basis of a negative PET-CT, and confirmative invasive staging should be performed in most patients before mediastinal metastasis is confirmed or ruled out.

FDG PET/CT in cancer: comparison of actual use with literature-based recommendations.

PURPOSE: The Region of Southern Denmark (RSD), covering 1.2 of Denmark's 5.6 million inhabitants, established a task force to (1) retrieve literature evidence for the clinical use of positron emission tomography (PET)/CT and provide consequent recommendations and further to (2) compare the actual use of PET/CT in the RSD with these recommendations. This article summarizes the results. METHODS: A Work Group appointed a professional Subgroup which made Clinician Groups conduct literature reviews on six selected cancers responsible for 5,768 (62.6 %) of 9,213 PET/CT scans in the RSD in 2012. Rapid Evidence Assessment was applied, using the methodology of systematic reviews with predefined limitations to search PubMed, Embase and the Cochrane Library for articles published in English/Danish/Swedish/Norwegian since 2002. PICO questions were defined, data recorded and quality appraised and rated with regard to strength and evidence level. Consequent recommendations for applications of PET/CT were established. The actual use of PET/CT was compared with these, where grades A and B indicated "established" and "useful" and grades C and D "potentially useful" and "non-recommendable" indications, respectively. RESULTS: Of 11,729 citations, 1,729 were considered for review, and 204 were included. The evidence suggested usefulness of PET/CT in lung, lymphoma, melanoma, head and neck, and colorectal cancers, whereas evidence was sparse in gynaecological cancers. The agreement between actual use of PET/CT and literature-based recommendations was high in the first five mentioned cancers in that 96.2 % of scans were made for grade A or B indications versus only 22.2 % in gynaecological cancers. CONCLUSION: Evidence-based usefulness was reported in five of six selected cancers; evidence was sparse in the sixth, gynaecological cancers. Actual use of PET/CT agreed well with recommendations.

Effect of phototherapy with turquoise vs. blue LED light of equal irradiance in jaundiced neonates.

BACKGROUND: Blue light with peak emission around 460 nm is the preferred treatment of neonatal hyperbilirubinemia. However, studies using fluorescent light tubes have suggested that turquoise light with peak emission at 490 nm may be more efficient. At present, the predominant light source for phototherapy is light emitting diodes (LEDs). Hence, the aim of this study was to compare the bilirubin-reducing effect in jaundiced neonates treated either with turquoise or with blue LED light with peak emission at 497 or 459 nm, respectively, with equal irradiance on the infants. METHODS: Infants with gestational age ≥33 wk and uncomplicated hyperbilirubinemia were randomized to either turquoise or blue LED light and were treated for 24 h. The mean irradiance footprint at skin level was 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. RESULTS: Forty-six infants received turquoise light and 45 received blue light. The median (95% confidence interval) decrease of total serum bilirubin was 35.3% (32.5; 37.3) and 33.1% (27.1; 36.8) for infants treated with turquoise and blue lights, respectively. The difference was nonsignificant (P = 0.53). The decrease was positively correlated to postnatal age and negatively to birth weight. CONCLUSION: Using LED light of equal irradiance, turquoise and blue lights had equal bilirubin-reducing effect on hyperbilirubinemia of neonates.

Bilirubin isomer distribution in jaundiced neonates during phototherapy with LED light centered at 497 nm (turquoise) vs. 459 nm (blue).

BACKGROUND: Phototherapy using blue light is the treatment of choice worldwide for neonatal hyperbilirubinemia. However, treatment with turquoise light may be a desirable alternative. Therefore, the aim of this randomized, controlled study was to compare the bilirubin isomer distribution in serum of jaundiced neonates after 24 h of therapy with narrow-band (LED) light centered at 497 nm (turquoise) vs. 459 nm (blue), of essentially equal irradiance. MATERIALS: Eighty-three neonates (≥33 wk gestational age) with uncomplicated hyperbilirubinemia were included in the study. Forty neonates were exposed to light centered at 497 nm and 43 infants with light centered at 459 nm. Irradiances were 5.2 × 10(15) and 5.1 × 10(15) photons/cm(2)/s, respectively. RESULTS: After 24 h of treatment no significant differences in serum concentrations of total bilirubin isomers and Z,Z-bilirubin were observed between the 2 groups. Interestingly, concentrations of Z,E-bilirubin, and thus also total bilirubin isomers formed during therapy, were highest for infants receiving light centered at 459 nm, while the concentration of E,Z-bilirubin was highest for those receiving light centered at 497 nm. No significant difference was found between concentrations of E,Z-lumirubin. CONCLUSION: Therapy with LED light centered at 497 nm vs. 459 nm, applied with equal irradiance on the infants, resulted in a different distribution of bilirubin isomers in serum.

Early formation of bilirubin isomers during phototherapy for neonatal jaundice: effects of single vs. double fluorescent lamps vs. photodiodes.

BACKGROUND: In neonatal jaundice, phototherapy converts bilirubin to more polar photoisomers which can be excreted without conjugation. We measured changes in the concentration of bilirubin Z,E-photoisomer during the first 4 h of intensive phototherapy using single fluorescent lights as a reference, compared to double fluorescent lights, and a single unit of photodiodes. METHODS: Neonates (N = 42; birth weight: 1,200-4,690 g; gestational age: 28-42 wk) were studied during phototherapy. Infants were randomized to: (i) single, or (ii) double fluorescent phototherapy; or (iii) single unit photodiodes. Irradiance was measured. Serum bilirubin (by cooximetry) and Z,E bilirubin (by high-pressure liquid chromatography) were measured at 0,15, 30, 60, 120, and 240 min after the start of phototherapy. Data were analyzed with a linear mixed model. RESULTS: There was a highly significant increase of Z,E-bilirubin over time (P < 0.0001), starting at 15 min. Photoisomers reached ~25% of total bilirubin concentration after 4 h. However, there were no significant differences between the three randomized groups in spite of significantly higher irradiance using double fluorescent lights vs. single fluorescent or photodiodes. CONCLUSION: Formation of bilirubin photoisomers is rapid, and occurs early during intensive phototherapy for neonatal jaundice. The rate and level of photoisomerization was not influenced by irradiance and light source.

Machine learning in diagnostic support in medical emergency departments.

Diagnosing patients in the medical emergency department is complex and this is expected to increase in many countries due to an ageing population. In this study we investigate the feasibility of training machine learning algorithms to assist physicians handling the complex situation in the medical emergency departments. This is expected to reduce diagnostic errors and improve patient logistics and outcome. We included a total of 9,190 consecutive patient admissions diagnosed and treated in two hospitals in this cohort study. Patients had a biochemical workup including blood and urine analyses on clinical decision totaling 260 analyses. After adding nurse-registered data we trained 19 machine learning algorithms on a random 80% sample of the patients and validated the results on the remaining 20%. We trained algorithms for 19 different patient outcomes including the main outcomes death in 7 (Area under the Curve (AUC) 91.4%) and 30 days (AUC 91.3%) and safe-discharge(AUC 87.3%). The various algorithms obtained areas under the Receiver Operating Characteristics -curves in the range of 71.8-96.3% in the holdout cohort (68.3-98.2% in the training cohort). Performing this list of biochemical analyses at admission also reduced the number of subsequent venipunctures within 24 h from patient admittance by 22%. We have shown that it is possible to develop a list of machine-learning algorithms with high AUC for use in medical emergency departments. Moreover, the study showed that it is possible to reduce the number of venipunctures in this cohort.

Positron emission tomography in chronic obstructive pulmonary disease.

The purpose of this paper was to systematically search the literature on (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) in the management of chronic obstructive pulmonary disease (COPD) and to provide a concise review of the reported results. Papers were searched through PubMed, EMBASE and Cochrane Library using the MESH terms "pulmonary disease, chronic obstructive", "pulmonary emphysema", and "positron-emission tomography". Of the 38 citations from the search and from browsing the literature lists of selected articles, seven relevant reports were identified. The sparse and heterogeneous literature available provide some indication that (18)F-FDG-PET could prove useful in COPD by a) differentiating COPD from chronic asthma and alpha-1-antitrypsin deficiency, b) measuring pulmonary and systemic inflammation to guide treatment and estimate prognosis, c) quantifying respiratory muscle use, and d) diagnosing cor pulmonale. In conclusion, the role of (18)F-FDG-PET in diagnosing and managing COPD patients seems to be promising and deserves to be further studied.

Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with localized pancreatic ductal adenocarcinoma.

Introduction: Current prognostic blood-based biomarkers for pancreatic adenocarcinoma (PDAC) are limited. Recently, promoter hypermethylation of SFRP1 (phSFRP1) has been linked to poor prognosis in patients with gemcitabine-treated stage IV PDAC. This study explores the effects of phSFRP1 in patients with lower stage PDAC. Methods: Based on a bisulfite treatment process, the promoter region of the SFRP1 gene was analyzed with methylation-specific PCR. Kaplan-Meier curves, log-rank tests, and generalized linear regression analysis were used to assess restricted mean survival time survival at 12 and 24 months. Results: The study included 211 patients with stage I-II PDAC. The median overall survival of patients with phSFRP1 was 13.1 months, compared to 19.6 months in patients with unmethylated SFRP1 (umSFRP1). In adjusted analysis, phSFRP1 was associated with a loss of 1.15 months (95%CI -2.11, -0.20) and 2.71 months (95%CI -2.71, -0.45) of life at 12 and 24 months, respectively. There was no significant effect of phSFRP1 on disease-free or progression-free survival. In stage I-II PDAC, patients with phSFRP1 have worse prognoses than patients with umSFRP1. Discussion: Results could indicate that the poor prognosis may be caused by reduced benefit from adjuvant chemotherapy. SFRP1 may help guide the clinician and be a possible target for epigenetically modifying drugs.

Scanner agnostic large-scale evaluation of MS lesion delineation tool for clinical MRI.

Introduction: Patients with MS are MRI scanned continuously throughout their disease course resulting in a large manual workload for radiologists which includes lesion detection and size estimation. Though many models for automatic lesion segmentation have been published, few are used broadly in clinic today, as there is a lack of testing on clinical datasets. By collecting a large, heterogeneous training dataset directly from our MS clinic we aim to present a model which is robust to different scanner protocols and artefacts and which only uses MRI modalities present in routine clinical examinations. Methods: We retrospectively included 746 patients from routine examinations at our MS clinic. The inclusion criteria included acquisition at one of seven different scanners and an MRI protocol including 2D or 3D T2-w FLAIR, T2-w and T1-w images. Reference lesion masks on the training (n = 571) and validation (n = 70) datasets were generated using a preliminary segmentation model and subsequent manual correction. The test dataset (n = 100) was manually delineated. Our segmentation model https://github.com/CAAI/AIMS/ was based on the popular nnU-Net, which has won several biomedical segmentation challenges. We tested our model against the published segmentation models HD-MS-Lesions, which is also based on nnU-Net, trained with a more homogenous patient cohort. We furthermore tested model robustness to data from unseen scanners by performing a leave-one-scanner-out experiment. Results: We found that our model was able to segment MS white matter lesions with a performance comparable to literature: DSC = 0.68, precision = 0.90, recall = 0.70, f1 = 0.78. Furthermore, the model outperformed HD-MS-Lesions in all metrics except precision = 0.96. In the leave-one-scanner-out experiment there was no significant change in performance (p < 0.05) between any of the models which were only trained on part of the dataset and the full segmentation model. Conclusion: In conclusion we have seen, that by including a large, heterogeneous dataset emulating clinical reality, we have trained a segmentation model which maintains a high segmentation performance while being robust to data from unseen scanners. This broadens the applicability of the model in clinic and paves the way for clinical implementation.