Chronic abdominal pain is highly prevalent in IBD patients in remission. The aetiology is incompletely understood, although persistent histologic inflammation, post-inflammatory visceral hypersensitivity, and altered gut-brain interaction are believed to contribute. Data on the characteristics of IBD patients suffering from chronic abdominal pain are sparse, yet essential for the identification of treatment targets. We investigated clinical, lifestyle and psychosocial factors associated with chronic abdominal pain in a real-world cohort of IBD patients in remission. A prospective multicentre study was performed enrolling consecutive IBD patients, between Jan 1, 2020 and Jul 1, 2021, using myIBDcoach, an established remote monitoring platform for IBD. Patient reported outcome measures on disease activity, lifestyle and psychosocial factors (i.e. depressive symptoms, anxiety, stress, and life events) were assessed in three-monthly intervals. Chronic abdominal pain in IBD in remission (IBDremissionPain+) was defined as an abdominal pain score ≥3 (1–10 numeric rating scale (NRS)) at ≥1/3 of all assessments combined with faecal calprotectin <150 μg/g in 90 days around periodic assessments. Multivariable logistic regression, adjusting for relevant confounders, was performed to identify risk factors for IBDremissionPain+ compared to patients in remission without chronic abdominal pain (IBDremissionPain-). In total, 559 patients were followed prospectively, of which 429 (76.7%) were in biochemical remission. Of these, 198 (46.2%) fulfilled the criteria for chronic abdominal pain. IBDremissionPain+ patients were characterized by female sex, higher BMI, and shorter disease duration compared to IBDremissionPain- (Table 1). IBDremissionPain+ patients reported significantly higher levels of stress, fatigue, depressive and anxiety symptoms, and occurrence of life events (Table 2). On multivariable logistic regression, female sex (aOR 2.58), shorter disease duration (<10years, aOR 2.31), higher BMI (aOR 1.06), higher levels of stress (aOR 1.19), fatigue (aOR 4.73), and life events (aOR 1.65) were all significantly associated with chronic abdominal pain (Table 3). The univariable association between pain and anxiety and depressive symptoms was modulated by stress in the multivariable analysis. In this real-world population of IBD patients in remission, 46.2% experience chronic abdominal pain, characterized by female sex, shorter disease duration, higher BMI, fatigue and psychosocial factors. The gut-brain interaction in this population is represented by higher levels of depressive and anxiety symptoms, but the relation to abdominal pain is potentially modulated through increased levels of perceived stress.

Iron deficiency (ID) and anaemia in Inflammatory Bowel Disease (IBD) are associated with reduced quality of life, worse disease outcomes, and an increase in healthcare costs. In the European guidelines, anaemia is listed as one of the treatment goals. The data on the prevalence of anaemia and ID are inconsistent. Therefore, we evaluated the prevalence of ID, anaemia, and potential risk factors in a large Dutch outpatient population. Between January and November 2021, consecutive adult outpatients with IBD, who did not have significant comorbidities associated with anaemia, were included in this study across 16 general, teaching, and academic hospitals within the Netherlands. Besides demographic and clinical data, relevant biochemical parameters such as haemoglobin (Hb), Mean Corpuscular Volume (MCV), iron indices, and inflammatory markers (e.g., C-reactive protein (CRP) and faecal calprotectin (FCP)) were extracted from medical records. Active IBD was defined by either CRP >5mg/L or FCP >150mg/g. ID was defined by ferritin <100µg/L in case of inflammation and <30µg/L in quiescent IBD, or transferrin saturation <20%. The Dutch national reference range was used to define anaemia: Hb <7.5mmol/L or <8.5mmol/L for females and males, respectively. The data were analysed by stratifying patients into Crohn’s Disease (CD) and Ulcerative Colitis (UC) groups, with the latter also including patients with IBD-unclassified (IBDU). In total, 2197 patients (1271 CD, 849 UC, and 77 IBDU) were included in the study. The overall prevalence of anaemia, iron-deficiency anaemia (IDA), and ID was: 18.0%, 12.2%, and 43.4%, respectively. The prevalence of all three conditions did not differ between the CD and UC groups (P>0.05). Severe anaemia (Hb<6.2 mmol/L) was observed only in 28 patients. ID was more frequently observed in biochemically active IBD compared with quiescent IBD (70.8% versus 23.9%; P<0.001). Female gender, younger age, low MCV, and a twofold increase in biochemical inflammation were associated with ID development in multivariable analysis: Log2FCP [OR 1.39; 95% CI: 1.29–1.50; P<0.001] and Log2platelets [OR 1.85; 95% CI: 1.16–2.95; P<0.01]. In multivariable analysis, low ferritin and MCV, inflammation, older age, and male gender were associated with a higher risk of anaemia; however, disease location or behaviour did not affect the risk of developing anaemia or ID. One in five ambulatory IBD patients presents with anaemia that is primarily caused by ID. Inflammation increases the risk of ID and anaemia regardless of IBD type or disease location. High ID prevalence suggests the need for screening and treatment optimisation.

Inflammatory bowel disease (IBD) is associated with malnutrition, which can further impair disease course and quality of life. Therefore, guidelines advocate screening of patients in clinical practice. The prevalence of malnutrition in IBD-cohorts however, varies widely, mainly due to differences in parameters used. The primary aim of the present study was to assess the prevalence of malnutrition using single and a combined set of parameters (Global Leadership Initiative on Malnutrition (GLIM) criteria). Secondary aims were i) to evaluate the accuracy of screening recommendations given in current IBD guidelines and ii) to explore which patients have an increased risk of malnutrition. Malnutrition was defined by the GLIM criteria, based on the combination of a phenotypic (i.e. non-volitional weight loss, low body mass index (BMI), or reduced muscle mass) and an etiologic criterium (i.e. reduced food intake or assimilation, and disease burden or inflammation). Malnutrition was also determined using single parameters for impaired body composition, muscle strength or caloric intake (Table 1), and the combination of low BMI and unintentional weight loss as advised in current IBD guidelines. To screen for malnutrition, the Short Nutritional Assessment Questionnaire (SNAQ) and Malnutrition Universal Screening Tool (MUST) were completed. Independent risk factors (i.e. clinical and demographic factors) for malnutrition were analyzed by multivariable logistic regression. Of the 200 included patients (139 CD, 61 UC), 41 (20.5%) fulfilled the GLIM criteria, 95 (47.5%) had at least one parameter for malnutrition impaired (Figure 1). The fat free mass index was most often affected. When unintentional weight loss and/or low BMI was used as screening marker for nutritional status in line with current IBD guidelines, 29 (14.5%) patients would have been identified (Figure 2). Screening for malnutrition using the SNAQ and MUST detected 44 (22.0%) and 23 (12.9%) patients with a positive score. Only female sex was associated with malnutrition when at least one parameter was impaired (OR 2.47, 95% CI 1.35–4.51). Malnutrition prevalence among IBD outpatients according to the GLIM criteria was found to be 20.5%. Almost half of the IBD outpatients had malnutrition as defined by various single parameters and irrespective of disease characteristics. Screening instruments and/or markers according to current IBD guidelines, did not identify a substantial part of the patients. Therefore, screening for malnutrition is recommended for all IBD outpatients by multiple parameters, with special attention for assessing fat free mass and reduced intake.

Acute secondary progressive multiple sclerosis (SPMS) is characterized by escalating neurological disability, with limited disease-modifying therapeutic options. A 48-year-old woman with acute SPMS being treated with interferon beta-1a and oral corticosteroids presented as a clinical outpatient with no disease-modifying effects after treatment. A decision was made to treat her with a combination of guanidinoacetate and creatine for 21 days. She had made clinical progress at follow-up, with the intensity of fatigue dropping from severe to mild. Magnetic resonance spectroscopy revealed increased brain choline, creatine, N-acetylaspartate, and glutathione. Patients with SPMS may benefit from guanidinoacetate–creatine treatment in terms of patient- and clinician-reported outcomes; this requires additional study.

Abstract STUDY QUESTION What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2018 as compared to previous years? SUMMARY ANSWER The 22nd ESHRE report shows a continued increase in reported numbers of ART treatment cycles and children born in Europe, a decrease in transfers with more than one embryo with a further reduction of twin delivery rates (DRs) as compared to 2017, higher DRs per transfer after fresh IVF or ICSI cycles (without considering freeze-all cycles) than after frozen embryo transfer (FET) with higher pregnancy rates (PRs) after FET and the number of reported IUI cycles decreased while their PR and DR remained stable. WHAT IS KNOWN ALREADY ART aggregated data generated by national registries, clinics or professional societies have been gathered and analysed by the European IVF-monitoring Consortium (EIM) since 1997 and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE on a yearly basis. The data on treatment cycles performed between 1 January and 31 December 2018 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons of 39 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1422 clinics offering ART services in 39 countries reported a total of more than 1 million (1 007 598) treatment cycles for the first time, including 162 837 with IVF, 400 375 with ICSI, 309 475 with FET, 48 294 with preimplantation genetic testing, 80 641 with egg donation (ED), 532 with IVM of oocytes and 5444 cycles with frozen oocyte replacement (FOR). A total of 1271 institutions reported data on IUI cycles using either husband/partner’s semen (IUI-H; n = 148 143) or donor semen (IUI-D; n = 50 609) in 31 countries and 25 countries, respectively. Sixteen countries reported 20 994 interventions in pre- and post-pubertal patients for FP including oocyte, ovarian tissue, semen and testicular tissue banking. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries (21 in 2017) in which all ART clinics reported to the registry, 410 190 treatment cycles were registered for a total population of ∼ 300 million inhabitants, allowing a best estimate of a mean of 1433 cycles performed per million inhabitants (range: 641–3549). Among the 39 reporting countries, for IVF, the clinical PR per aspiration slightly decreased while the PR per transfer remained similar compared to 2017 (25.5% and 34.1% in 2018 versus 26.8% and 34.3% in 2017). In ICSI, the corresponding rates showed similar evolutions in 2018 compared to 2017 (22.5% and 32.1% in 2018 versus 24.0% and 33.5% in 2017). When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.8% (29.4% in 2017) and 27.3% (27.3% in 2017) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was 33.4% (versus 30.2% in 2017), and with embryos originating from donated eggs 41.8% (41.1% in 2017). After ED, the PR per fresh embryo transfer was 49.6% (49.2% in 2017) and per FOR 44.9% (43.3% in 2017). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 50.7%, 45.1%, 3.9% and 0.3% of all treatments, respectively (corresponding to 46.0%, 49.2%. 4.5% and 0.3% in 2017). This resulted in a reduced proportion of twin DRs of 12.4% (14.2% in 2017) and similar triplet DR of 0.2%. Treatments with FET in 2018 resulted in twin and triplet DRs of 9.4% and 0.1%, respectively (versus 11.2% and 0.2%, respectively in 2017). After IUI, the DRs remained similar at 8.8% after IUI-H (8.7% in 2017) and at 12.6% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%), and 6.4% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). Among 20 994 FP interventions in 16 countries (18 888 in 13 countries in 2017), cryopreservation of ejaculated sperm (n = 10 503, versus 11 112 in 2017) and of oocytes (n = 9123 versus 6588 in 2017) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION The results should be interpreted with caution as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 22nd ESHRE data collection on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts towards optimization of both the collection and reporting, with the aim of improving surveillance and vigilance in the field of reproductive medicine, are awaited. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

Introduction: Serum creatinine is not enough sensitive marker for the evaluation of glomerular filtration rate (GFR). Cockcroft-Gault (CG) formula is often used to assess GFR, but it is necessary to correct original one for body surface area (BSA), adipositas, and the creatinine tubular secretion. The values of the estimated creatinine clearance and GFR are considered to Poggio reference ones according to biological parameters (age and gender). The aim of the study was to determine the difference in renal function estimation between serum creatinine and corrected CG equation according to the Poggio reference values in the arterial hypertension patients. Materials and Methods: The research included 124 patients of both gender with arterial hypertension, excluding ones with the already verified chronic kidney disease. We estimated creatinine clearance and GFR by CG method corrected for the BSA, body mass index (BMI), and the creatinine tubular secretion according to Poggio reference values. Results: There was no significant difference in both age and gender groups among patients with physiological and pathological values of the renal function determined by the serum creatinine and estimated creatinine clearance by CG equation corrected for BMI, BSA. In both age and gender groups there was significant difference among subjects with physiological and pathological values of the renal function determined by serum creatinine and estimated GFR by CG method corrected for BMI, BSA, and creatinine tubular secretion. Conclusion: There is the most striking difference in the assessment of renal function between serum creatinine and estimated GFR by CG method with three corrections (BSA, BMI, the creatinine tubular secretion). Estimated GFR by CG method with three corrections can help in the early diagnosis of renal dysfunction and optimal treatment in patients with arterial hypertension.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

Additive manufacturing (AM) or "3D-printing" is a ground-breaking technology that enables the production of complex 3D parts. Its rapid growth calls for immediate toxicological investigations of possible human exposures in order to estimate occupational health risks. Several laser-based powder bed fusion AM techniques are available of which many use metal powder in the micrometer range as feedstock. Large energy input from the laser on metal powders generates several by-products, like spatter and condensate particles. Due to often altered physicochemical properties and composition, spatter and condensate particles can result in different toxicological responses compared to the original powder particles. The toxicity of such particles has, however, not yet been investigated. The aim of the present study was to investigate the toxicity of condensate/spatter particles formed and collected upon selective laser melting (SLM) printing of metal alloy powders, including a nickel-chromium-based superalloy (IN939), a nickel-based alloy (Hastelloy X, HX), a high-strength maraging steel (18Ni300), a stainless steel (316 L), and a titanium alloy (Ti6Al4V). Toxicological endpoints investigated included cytotoxicity, generation of reactive oxygen species (ROS), genotoxicity (comet and micronucleus formation), and inflammatory response (cytokine/chemokine profiling) following exposure of human bronchial epithelial cells (HBEC) or monocytes/macrophages (THP-1). The results showed no or minor cytotoxicity in the doses tested (10-100 μg/mL). Furthermore, no ROS generation or formation of micronucleus was observed in the HBEC cells. However, an increase in DNA strand breaks (detected by comet assay) was noted in cells exposed to HX, IN939, and Ti6Al4V, whereas no evident release of pro-inflammatory cytokine was observed from macrophages. Particle and surface characterization showed agglomeration in solution and different surface oxide compositions compared to the nominal bulk content. The extent of released nickel was small and related to the nickel content of the surface oxides, which was largely different from the bulk content. This may explain the limited toxicity found despite the high Ni bulk content of several powders. Taken together, this study suggests relatively low acute toxicity of condensates/spatter particles formed during SLM-printing using IN939, HX, 18Ni300, 316 L, and Ti6Al4V as original metal powders.

PURPOSE To report on the use of human amniotic membrane (hAM) for macular holes at two Canadian tertiary care centres. DESIGN Retrospective cohort study. SUBJECTS 22 patients with persistent or chronic macular holes. METHODS Macular hole surgery was performed by three vitreoretinal surgeons. MAIN OUTCOMES Macular hole closure with complete plugging by hAM on SD-OCT. RESULTS The closure rate was 91% (20/22, median follow-up 7 months) with no statistically significant visual acuity change overall. Complications included subretinal silicone oil (5%), choroidal neovascularization (5%), atrophy (5%), and cystoid macular edema (9%). CONCLUSIONS Anatomical success with limited visual recovery was observed.

Population‐level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data‐driven manner, leading to uncertainty when classifying low‐titer responses. To improve upon this, we evaluated cutoff‐independent methods for their ability to assign likelihood of SARS‐CoV‐2 seropositivity to individual samples.