Antiphospholipid antibodies and antiphospholipid syndrome.

Individuals with antiphospholipid syndrome (APS) have antibodies directed against phospholipid-binding proteins (aPL). The condition is most associated with an increased risk of thromboembolism and obstetric complications. The 2023 classification criteria for APS include six clinical domains (venous thromboembolism, arterial thrombosis, microvascular events, obstetric events, cardiac valve, thrombocytopaenia) and two laboratory domains (lupus anticoagulant, and anti-cardiolipin or anti-ß2-glycoprotein-I antibodies). Diagnosis and treatment of APS are specialist tasks and are summarised in this review.

Epidemiological description and trajectories of patients with prostate cancer in Denmark: an observational study of 7448 patients.

OBJECTIVE: Identification of patients at high risk of aggressive prostate cancer is a major clinical challenge. With the view of developing artificial intelligence-based methods for identification of these patients, we are constructing a comprehensive clinical database including 7448 prostate cancer (PCa) Danish patients. In this paper we provide an epidemiological description and patients' trajectories of this retrospective observational population, to contribute to the understanding of the characteristics and pathways of PCa patients in Denmark. RESULTS: Individuals receiving a PCa diagnosis during 2008-2014 in Region Southern Denmark were identified, and all diagnoses, operations, investigations, and biochemistry analyses, from 4 years prior, to 5 years after PCa diagnosis were obtained. About 85.1% were not diagnosed with metastatic PCa during the study period (unaggressive PCa); 9.2% were simultaneously diagnosed with PCa and metastasis (aggressive-advanced PCa), while 5.7% were not diagnosed with metastatic PCa at first, but they were diagnosed with metastasis at some point during the 5 years follow-up (aggressive-not advanced PCa). Patients with unaggressive PCa had more clinical investigations directly related to PCa detection (prostate ultrasounds and biopsies) during the 4 years prior to PCa diagnosis, compared to patients with aggressive PCa, which may have contributed to the early detection of PCa.

Comparison of plasma total carbon dioxide and standard hydrogen carbonate in a hospital laboratory setting.

BACKGROUND: Studies comparing venous total carbon dioxide (tCO2) and standard hydrogen carbonate (HCO3-(P,st)) has shown diverse results, and it is debatable whether these two parameters can be used interchangeably for workup of acid-base disorders in a hospital setting. METHOD: All patients with an HCO3-(P,st) requisition from any department at Odense University Hospital between 11th May 2021 and 1st June 2021 had tCO2 and HCO3-(P,st) analysed simultaneously. TCO2 was measured on Cobas® 8000, c702 module, while HCO3-(P,st) was calculated based on measurements on ABL835 Flex. RESULTS: From 1210 patients, mean (standard deviation (SD)) was 22.9 (3.7) mmol/L for tCO2 and 22.5 (2.9) mmol/L for HCO3-(P,st). TCO2 range was 10.1-42.3 mmol/L and 11.7-41.4 mmol/L for HCO3-(P,st). Linear regression showed that tCO2 (mmol/L) = -2.90 + 1.15 × HCO3-(P,st) (mmol/L) with R2 = 0.81. Bias (mean (SD) difference) between tCO2 and HCO3-(P,st)) was 0.4 (1.7) mmol/L with a -5.0-9.6 mmol/L range. Limits of agreement was -2.90-3.70 mmol/L. Comparison of classification within, above or below reference interval for tCO2 and HCO3-(P,st) showed that 984 samples (81%) retained their classification. Only one sample (0.1%) would be severely misclassified (outside the respective reference intervals) if HCO3-(P,st) was considered the gold standard. Of the samples investigated, 46.1% had a mean difference between tCO2 and HCO3-(P,st) of 0-1 mmol/L and 30.3% had 1.1-2.0 mmol/L. CONCLUSIONS: Our results indicate that venous tCO2 and venous HCO3-(P,st) can be used interchangeably in a hospital setting for workup of acid-base disorders.

Prevalence of Bleeding Symptoms in Denmark Using the Patient-administered Bleeding Assessment Tool (self-BAT).

INTRODUCTION: The patient-administered bleeding assessment tool (self-BAT) is a screening tool developed to identify individuals in need of work-up for bleeding disorders. Nonetheless, large studies on self-BAT scores on healthy individuals according to gender and age are lacking. AIM: Determine cut-offs for abnormal total score of self-BAT and investigate the prevalence of bleeding symptoms in blood donors and individuals representative of the general Danish population. METHODS: Blood donors, 15,600 children (<18 years) and 18,200 adults from the general Danish population, were invited to complete a Danish version of the self-BAT. To determine cut-offs for abnormal total self-BAT score, findings from healthy young children (0-11 years old), healthy adolescents (12-17 years old), healthy adult women and healthy adult men were used. RESULTS: Among healthy young children (244 girls, 260 boys), healthy adolescents (58 girls, 83 boys), healthy women (n = 437) and healthy men (n = 278) from the general population, along with healthy blood donors (116 women, 176 men), the 95th percentile for total score was two for young girls, three for young boys, four for adolescent girls, three for adolescent boys, eight for women and four for men. CONCLUSION: Our findings indicate that the abnormal total self-BAT score is ≥3 for girls aged 0-11 years old, ≥4 for boys aged 0-11 years old, ≥5 for girls aged 12-17 years old, ≥4 for boys aged 12-17 years old, ≥9 for women and ≥5 for men. To establish the accuracy of these cut-offs for diagnosing bleeding disorders, further studies are needed.

Prevalence of prostate cancer in men with haematuria: a systematic review and meta-analysis.

OBJECTIVES: To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed. METHODS: The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer. RESULTS: We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0-4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9-9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8-2.2%; n = 71/6642). CONCLUSION: Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria.

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study.

BACKGROUND: Basement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome. METHODS: Human arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)). RESULTS: We first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients. CONCLUSION: Our results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

Venous Thromboembolism in Pediatric Cancer Patients with Central Venous Catheter-A Systematic Review and Meta-analysis.

Pediatric cancer patients hold an increased risk of venous thromboembolism (VTE) due to their cancer. Central venous catheters (CVCs) further increase the VTE risk. This systematic literature review elucidates the VTE incidence in pediatric cancer patients with CVC. MEDLINE and EMBASE were searched in August 2020 without time limits. We included studies reporting original data on patients ≤18 years with any CVC type and any cancer type, who were examined for VTE with ≥7 days follow-up. In total, 682 unique records were identified, whereof 189 studies were assessed in full text. Altogether, 25 studies were included, containing 2,318 pediatric cancer patients with CVC, of which 17% suffered VTE. Fifteen studies (n = 1,551) described CVC-related VTE and reported 11% CVC-related VTE. Concerning cancer type, 991 children suffered from acute lymphoblastic leukemia (ALL) and 616 from solid tumors. Meta-analysis revealed VTE incidence (95% confidence interval) of 21% (8-37) for ALL and 7% (0.1-17) for solid tumors. Additionally, 20% of children with tunneled or nontunneled CVC and 12% of children with implantable ports suffered VTE. In conclusion, pediatric cancer patients with CVC have substantial VTE risk. Children with ALL and CVC have higher VTE incidence than children with solid tumors and CVC. Implantable port catheter should be preferred over tunneled or nontunneled CVC to reduce VTE risk. Thrombophilia investigation does not seem relevant in pediatric cancer patients with CVC and VTE. To prevent VTE, intensified catheter care is recommended, especially in children with ALL.

Deep learning detects and visualizes bleeding events in electronic health records.

BACKGROUND: Bleeding is associated with a significantly increased morbidity and mortality. Bleeding events are often described in the unstructured text of electronic health records, which makes them difficult to identify by manual inspection. OBJECTIVES: To develop a deep learning model that detects and visualizes bleeding events in electronic health records. PATIENTS/METHODS: Three hundred electronic health records with International Classification of Diseases, Tenth Revision diagnosis codes for bleeding or leukemia were extracted. Each sentence in the electronic health record was annotated as positive or negative for bleeding. The annotated sentences were used to develop a deep learning model that detects bleeding at sentence and note level. RESULTS: On a balanced test set of 1178   sentences, the best-performing deep learning model achieved a sensitivity of 0.90, specificity of 0.90, and negative predictive value of 0.90. On a test set consisting of 700 notes, of which 49 were positive for bleeding, the model achieved a note-level sensitivity of 1.00, specificity of 0.52, and negative predictive value of 1.00. By using a sentence-level model on a note level, the model can explain its predictions by visualizing the exact sentence in a note that contains information regarding bleeding. Moreover, we found that the model performed consistently well across different types of bleedings. CONCLUSIONS: A deep learning model can be used to detect and visualize bleeding events in the free text of electronic health records. The deep learning model can thus facilitate systematic assessment of bleeding risk, and thereby optimize patient care and safety.

Pseudohyponatraemia caused by acute pancreatitis-derived hypertriglyceridaemia.

We report a case of pseudohyponatraemia due to severe hypertriglyceridaemia-induced acute pancreatitis, stemming from unknown diabetes. A woman in her late 30s was admitted to the local hospital by her general practitioner due to severe hyponatraemia (116 mmol/L) and upper abdominal pain. At admission to the hospital, there was a discrepancy of 19 mmol/L between arterial and venous sodium, along with severe hypertriglyceridaemia and hypercholesterolaemia. Pancreatitis was diagnosed using a CT scan. The patient received plasmapheresis which significantly reduced triglycerides, and venous plasma sodium was normalised indicating pseudohyponatraemia at admission. Finally, a haemoglobin A1c of 83 mmol/mol was found. Diabetes was diagnosed, and insulin was initiated.

Translation, validation, and usability of the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool (Self-ISTH-BAT).

BACKGROUND: Bleeding questionnaires are effective and recommended screening tools for potential bleeding disorder, but healthcare practitioner-administered bleeding assessment tools (expert-ISTH-BATs) are time-consuming. A patient-administered ISTH-BAT (self-ISTH-BAT) has been developed and validated. We translated, validated, and evaluated the usability of self-ISTH-BAT. METHODS: We conducted a forward-backward translation of self-ISTH-BAT from English to Danish. Expert-ISTH-BAT and Danish self-ISTH-BAT were administered to 106 random individuals aged ≥18 years attending Odense University Hospital between August and November 2020 for elective blood sampling. Results comprise a score of bleeding symptoms. RESULTS: Mean age of included individuals were 49 years (range: 18-83), and 59% were female. Median self-ISTH-BAT score was 2 (range: 0-18) and 1 (range: 0-22) for expert-ISTH-BAT (P = .09). All organ systems had ≥90% exact score agreement between expert-ISTH-BAT and self-ISTH-BAT, except gastrointestinal bleeding (77%) and other bleedings (72%). We found an acceptable correlation (r2  = .80) between expert-ISTH-BAT and self-ISTH-BAT. The self-ISTH-BAT had 82% sensitivity and 89% specificity at the recommended cutoff for expert-BAT (female:<6; male:<4). At this cutoff, 10 had abnormal self-ISTH-BAT scores with normal expert-ISTH-BAT. Three (3%) had normal self-ISTH-BAT with abnormal expert-ISTH-BAT. CONCLUSION: Self-ISTH-BAT can replace expert-ISTH-BAT as a screening tool for bleeding disorders in Danish individuals as only 3% were not identified with the self-ISTH-BAT tool.

The association between activated protein C ratio and Factor V Leiden are gender-dependent.

Background The most common cause of activated protein C (aPC) resistance is a missense substitution (Arg506Gln), known as Factor V Leiden (FVL). Due to its low cost, many laboratories use the aPC ratio as a primary test with a unisex cut-off. However, the association between the aPC ratio and FVL including any relation to gender has been sparsely investigated. Methods Results of the aPC ratio and FVL analyses from 1081 patients referred to the Thrombophilia Clinic at Odense University Hospital were compared. Results In 153 FVL positive patients, the mean aPC ratio was 2.1 ± 0.3, which differed from 2.7 ± 0.4 in FVL negative individuals (p < 0.01). The receiver operating characteristics (ROC), with area under the curve (AUC) of 0.93, indicated the optimal aPC cut-off at 2.3-2.4, with sensitivity 89%-94%, specificity 71%-84%, positive predictive value 35%-48% and negative predictive value 98%-99%. In FVL positive females, the mean aPC ratio was 2.0 ± 0.3, which differed from males (2.1 ± 0.3, p < 0.05). In FVL negative females, the mean aPC ratio was 2.6 ± 0.4, also different from males (2.8 ± 0.5, p < 0.01). Of note, 35% of FVL negative females had an aPC ratio ≤2.4 against 18% in males (p < 0.01). Conclusions Our results indicate that the aPC ratio is lower in females than in males. Due to a high negative predictive value the aPC ratio can be used as a first line test for FVL, but those found positive must be confirmed with a DNA test.

Small-incision lenticule extraction (SMILE): outcomes of 722 eyes treated for myopia and myopic astigmatism.

PURPOSE: To study the outcomes of small-incision lenticule extraction (SMILE) for treatment of myopia and myopic astigmatism. METHODS: Retrospective study of patients treated for myopia or myopic astigmatism with SMILE, using a VisuMax(®) femtosecond laser (Carl Zeiss Meditec, Jena, Germany), at the Department of Ophthalmology, Odense University Hospital, Odense, Denmark. Inclusion criteria were corrected distance visual acuity (CDVA) of 20/25 or better before surgery and no ocular conditions other than myopia up to -10.00 diopters (D) with astigmatism up to 3.00 D. RESULTS: Of the 729 treatments, 722 were included. The spherical equivalent (SE) refraction averaged -6.82 ± 1.66 diopters (D) before surgery. After 3 months, 88 % of eyes were within ±0.50 D of the intended refraction, whilst 98 % were within ±1.00 D. The mean difference between attempted and achieved SE refraction at 3 months after surgery was -0.06 ± 0.01 D (range: -1.25 to 1.25 D). In eyes with emmetropia as target refraction (n = 362), 63 % had uncorrected distance visual acuity (UDVA) of 20/25 or better 1 day after surgery, rising to 83 % at 3 months after surgery. The average gain in CDVA from before surgery to 3 months after surgery was 0.07 ± 0.03 (logMAR). However, 12 eyes (1.6 %) lost 2 or more lines of CDVA from before surgery to 3 months postoperatively. Simultaneous treatment of up to 3.00 D of astigmatism was not associated with less predictable refractive outcomes. CONCLUSIONS: In the short term, SMILE seemed predictable, efficient, and safe for treatment of myopia and myopic astigmatism.

Four-year to seven-year outcomes of advanced surface ablation with excimer laser for high myopia.

PURPOSE: We aimed to evaluate and compare outcomes after photorefractive keratectomy with cooling (cPRK) and laser-assisted subepithelial keratectomy (LASEK) for high myopia. METHODS: This was a retrospective, single-masked follow-up study of patients treated for myopia between 2007 and 2009 with cPRK or LASEK, using a high-frequency flying-spot excimer laser with eye-tracker (MEL80; Carl Zeiss, Jena, Germany). One eye of each patient was randomly chosen for analysis. Re-treated eyes were excluded. RESULTS: Forty-six cPRK patients and 35 LASEK patients were included. Spherical equivalent averaged -7.69 ± 1.47 diopters (D) in cPRK eyes and -7.98 ± 2.06 D in LASEK eyes (p = 0.31) before surgery. The average follow-up time was 4.6 years in cPRK patients and 6.0 years in LASEK patients (p < 0.05). At final follow-up, no cPRK eyes and one LASEK eye (p = 0.46) had lost two lines of corrected distance visual acuity (CDVA). No eyes had significant haze at final follow-up, although trace haze was found in four cPRK eyes and six LASEK eyes (p = 0.44). However, at 6 weeks after surgery, zero cPRK eyes and nine LASEK eyes (p < 0.05) had significant haze. At final follow-up, 63 % of cPRK eyes and 35 % of LASEK eyes (p = 0.17) were within ±1.0 D of intended refraction. Finally, 100 % of cPRK patients and 92 % of LASEK patients (p = 0.87) were satisfied or very satisfied with the surgery at final follow-up. CONCLUSION: cPRK and LASEK seemed safe and with high patient satisfaction 4 to 7 years after surgery for high myopia. However, cPRK was more effective than LASEK in reducing initial significant corneal haze.