SARS-CoV-2 antibody dynamics over time and risk factors associated with infection and long COVID-19 symptoms in large working environments.

BACKGROUND: Factors influencing SARS-CoV-2 antibody dynamics, transmission, waning and long COVID-19 symptomatology are still not fully understood. METHODS: In the Danish section of the Novo Nordisk Group, we performed a prospective seroepidemiological study during the first and second waves of the COVID-19 pandemic. All employees and their household members (>18 years) were invited to participate in a baseline (June-August 2020), 6-month follow-up (December 2020-January 2021), and 12-month follow-up (August 2021) sampling. In total, 18,614 accepted and provided at least one blood sample and completed a questionnaire regarding socioeconomic background, health status, previous SARS-CoV-2 infection, and persistent symptoms. Total antibody and specific IgM, IgG and IgA levels against recombinant receptor binding domain were tested. RESULTS: At baseline, the SARS-CoV-2-antibody seroprevalence was 3.9%. At 6-month follow-up, the seroprevalence was 9.1%, while at 12-month follow-up, the seroprevalence was 94.4% (after the vaccine roll-out). Male sex and younger age (18-40 years) were significant risk factors for seropositivity. From baseline to the 6-month sampling, we observed a substantial waning of IgM, IgG and IgA levels (p < 0.001), regardless of age, sex and initial antibody level. An increased antibody level was found in individuals infected prior to vaccination compared to vaccinated infection naïves (p < 0.0001). Approximately a third of the seropositive individuals reported one or more persistent COVID-19 symptoms, with anosmia and/or ageusia (17.5%) and fatigue (15.3%) being the most prevalent. CONCLUSION: The study provides a comprehensive insight into SARS-CoV-2 antibody seroprevalence following infection and vaccination, waning, persistent COVID-19 symptomatology and risk factors for seropositivity in large working environments.

Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study.

BACKGROUND: mRNA-based COVID-19 vaccines have short- and long-term efficacy in healthy individuals, but their efficacy in patients with psoriasis receiving immunomodulatory therapy is less studied. OBJECTIVES: To investigate long-term immunity after COVID-19 vaccination in patients with psoriasis receiving immunomodulatory therapy. METHODS: A prospective cohort study including patients (n = 123) with psoriasis receiving methotrexate (MTX) or biologics and controls (n = 226). Only mRNA-based COVID-19 vaccines administered with standard intervals between doses were investigated. Markers of immunity included SARS-CoV-2 spike glycoprotein-specific IgG and IgA, neutralizing capacity, and interferon-γ release from T cells stimulated with peptides of the SARS-CoV-2 spike glycoprotein. RESULTS: The proportion of IgG responders was lower 6 months after vaccination in patients receiving anti-tumour necrosis factor (TNF) treatment compared with controls. Anti-TNF treatment was associated with lower IgG levels (ß = -0.82, 95% confidence interval -1.38 to -0.25; P = 0.001). The median neutralizing index was lower in the anti-TNF group [50% inhibition (interquartile range [IQR] 37-89)] compared with controls [98% inhibition (IQR 96-99)]; P < 0.001. Cellular responses were numerically lowest in the anti-TNF group. CONCLUSIONS: Treatment with anti-TNF has an impact on the immunity elicited by mRNA-based COVID-19 vaccination in patients with psoriasis, resulting in a faster waning of humoral and cellular markers of immunity; however, the clinical implications are unknown.

Anti-Müllerian hormone and live birth in unexplained recurrent pregnancy loss.

RESEARCH QUESTION: Is anti-Müllerian hormone (AMH) associated with live birth rate (LBR) in women with unexplained recurrent pregnancy loss (RPL)? DESIGN: Cohort study of women with unexplained RPL attending the RPL Unit, Copenhagen University Hospital, Denmark, between 2015 and 2021. AMH concentration was assessed upon referral, and LBR in the next pregnancy. RPL was defined as three or more consecutive pregnancy losses. Regression analyses were adjusted for age, number of previous losses, body mass index, smoking, treatment with assisted reproductive technology (ART) and RPL treatments. RESULTS: A total of 629 women were included; 507 (80.6%) became pregnant after referral. Pregnancy rates were similar for women with low and high AMH compared to women with medium AMH (81.9, 80.3 and 79.7%, respectively) (low AMH: adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.84-2.47, P = 0.18; high AMH: aOR 0.98, 95% CI 0.59-1.64, P = 0.95). AMH concentrations were not associated with live birth. LBR was 59.5% in women with low AMH, 66.1% with medium AMH and 65.1% with high AMH (low AMH: aOR 0.68, 95% CI 0.41-1.11, P = 0.12, high AMH: aOR 0.96, 95% CI 0.59-1.56, P = 0.87). Live birth was lower in ART pregnancies (aOR 0.57, 95% CI 0.33-0.97, P = 0.04) and with higher numbers of previous losses (aOR 0.81, 95% CI 0.68-0.95, P = 0.01). CONCLUSION: In women with unexplained RPL, AMH was not associated with the chances of live birth in the next pregnancy. Screening for AMH in all women with RPL is not supported by current evidence. The chance of live birth among women with unexplained RPL achieving pregnancy by ART was low and needs to be confirmed and explored in future studies.

Humoral and cellular immune responses after three or four doses of BNT162b2 in patients with hematological malignancies.

OBJECTIVES: Initial responses to coronavirus disease 2019 vaccination are impaired in patients with hematological malignancies. We investigated immune responses after three or four doses of BNT162b2 in patients with myeloid and lymphoid malignancies compared to controls, and identified risk factors for humoral and cellular nonresponse 1 year after first vaccination. METHODS: In 407 hematological patients (45 myeloid, 362 lymphoid) and 98 matched controls, we measured immunoglobulin G (IgG) and neutralizing antibodies specific for the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at baseline, 3 weeks, 2, 6, and 12 months, and interferon-γ release at 12 months. RESULTS: In patients with lymphoid malignancies, SARS-CoV-2 receptor-binding domain IgG concentration and mean neutralizing capacity was lower than in controls at all time points. A diagnosis of chronic lymphocytic B-cell leukemia (CLL) or lymphoma was associated with humoral nonresponse at 12 months compared to having multiple myeloma/amyloidosis (p < .001 and p = .013). Compared to controls, patients with lymphoid malignancies had increased risk of cellular nonresponse. A lymphoma diagnosis was associated with lower risk of cellular nonresponse compared to patients with multiple myeloma/amyloidosis, while patients with CLL had comparable response rates to patients with multiple myeloma/amyloidosis (p = .037 and p = .280). CONCLUSIONS: In conclusion, long-term humoral and cellular immune responses to BNT162b2 were impaired in patients with lymphoid malignancies.

Effect of near infrared autofluorescence guided total thyroidectomy on postoperative hypoparathyroidism: a randomized clinical trial.

PURPOSE: The purpose of this single-blinded, 2-centre, randomized controlled trial was to test if near-infrared (NIR) autofluorescence image guidance for parathyroid gland (PG) detection during total thyroidectomy can reduce the incidence of hypoparathyroidism in both malignant and benign cases. METHOD: Patients admitted for primary or completion total thyroidectomy were randomized to either the NIR intervention group or the standard care NONIR (no near infrared) group. The primary endpoint was the rate of hypoparathyroidism at the 3-month follow-up, defined as hypocalcemia and inappropriately low parathyroid hormone levels and/or continuous treatment with active vitamin D. The secondary endpoint was the PG identification rate. RESULTS: A total of 147 patients were included of whom 73 were allocated to NIR. Primary or completion thyroidectomy was conducted in 84 and 63 cases, respectively. A total of 130 completed 3 months follow-up. Postoperative hypoparathyroidism in the NIR group at 12 h, 1 month and 3 months was, respectively, 31.8, 14.1, 6.5% compared with 35.9, 18.9, 11.8% in the NONIR group (all p > 0.46). In the NIR group, the identification rate of PGs was 69.5% (146 of 210 PGs), and 9% (19 of 210 PGs) were identified only due to additional use of NIR. For 15 out of 69 patients (21.7%) additionally PGs was found. CONCLUSION: Hypoparathyroidism was nominally less frequent in the NIR group, although not statistically significant. Further studies are needed to confirm if NIR may be a supportive PG identification tool to minimize the number of PG which would have been otherwise missed, especially during more complicated thyroid procedures. TRIAL REGISTRY: ClinicalTrials.gov: NCT04193332. Registration date: 16.08.2019.

Humoral response to two doses of BNT162b2 vaccination in people with HIV.

BACKGROUND: People with HIV (PWH) are at increased risk of severe COVID-19. We aimed to determine humoral responses in PWH and controls who received two doses of BNT162b2. METHODS: In 269 PWH and 538 age-matched controls, we measured IgG and neutralizing antibodies specific for the receptor-binding domain of SARS-CoV-2 at baseline, 3 weeks and 2 months after the first dose of BNT162b2. RESULTS: IgG antibodies increased from baseline to 3 weeks and from 3 weeks to 2 months in both groups, but the concentrations of IgG antibodies were lower in PWH than that in controls at 3 weeks and 2 months (p = 0.025 and <0.001), respectively. The IgG titres in PWH with a humoral response at 2 months were 77.9% (95% confidence interval [62.5%-97.0%], age- and sex-adjusted p = 0.027) of controls. CONCLUSIONS: Reduced IgG antibody response to vaccination with BNT162b2 was found in PWH, and thus increased awareness of breakthrough infections in PWH is needed.

The Accuracy of Hemoglobin A1c and Fructosamine Evaluated by Long-Term Continuous Glucose Monitoring in Patients with Type 2 Diabetes Undergoing Hemodialysis.

INTRODUCTION: The accuracy of hemoglobin A1c (HbA1c) as a glycemic marker in patients with type 2 diabetes (T2D) receiving hemodialysis (HD) remains unknown. To assess accuracy, we compared HbA1c and fructosamine levels with interstitial glucose measured by continuous glucose monitoring (CGM) in patients with T2D receiving HD. METHODS: Thirty patients in the HD group and 36 patients in the control group (T2D and an estimated glomerular filtration rate >60 mL/min/1.73 m2) completed the study period of 17 weeks. CGM (Ipro2®, Medtronic) was performed 5 times for periods of up to 7 days (with 4-week intervals) during a 16-week period. HbA1c (mmol/mol), the estimated mean plasma glucose from HbA1c (eMPGA1c [mmol/L]) and fructosamine (µmol/L) was measured at week 17 and compared with mean sensor glucose levels from CGM. FINDINGS: In the HD group, mean sensor glucose was 1.4 mmol/L (95% confidence interval [CI]: 1.0-1.8) higher than the eMPGA1c, whereas the difference for controls was 0.1 mmol/L (95% CI: -0.1-[0.4]; p < 0.001). Adjusted for mean sensor glucose, HbA1c was lower in the HD group (-7.3 mmol/mol, 95% CI: -10.0-[-4.7]) than in the control group (p < 0.001), with no difference detected for fructosamine (p = 0.64). DISCUSSION: HbA1c evaluated by CGM underestimates plasma glucose levels in patients receiving HD. The underestimation represents a clinical challenge in optimizing glycemic control in the HD population. Fructosamine is unaffected by the factors affecting HbA1c and appears to be more accurate for glycemic monitoring. CGM or fructosamine could thus complement HbA1c in obtaining more accurate glycemic control in this patient group.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Quantification of biotin in plasma samples by column switching liquid chromatography - tandem mass spectrometry.

Biotin (or Vitamin B7) is a vitamin where deficiency can be caused by inadequate intake. Biotin deficiency is rare, as most people get enough biotin from diet, since many foods contain biotin. In addition to biotin from food, intestinal bacteria can synthesize biotin, which can then be absorbed by the body. Supplementation with biotin has been advocated, mainly due to proposed beneficial effects on skin, nail and hair growth. There is no evidence that high biotin intakes are toxic, but a high intake may interfere with diagnostic assays that use biotin-streptavidin technology. These tests are commonly used to measure plasma concentrations of a wide range of hormones. Erroneous results may lead to misdiagnosis of various endocrine disorders. Supplementation with high-dose biotin has been used experimental for the treatment of diseases (e.g. multiple sclerosis) and high doses are used to obtain effect on nail and hair growth. On this background a demand for tests to determine if there is a risk of obtaining false test results when using biotin-streptavidin based tests have appeared. In this paper we present a method based on column switching liquid chromatography tandem mass spectrometry for the quantification of biotin in plasma and serum and explore the effects of biotin on an immunoassay based on biotin strept(avidin) chemistry.

Adrenal insufficiency in prednisolone-treated patients with polymyalgia rheumatica or giant cell arteritis-prevalence and clinical approach.

OBJECTIVES: Glucocorticoid treatment is fundamental in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA), but carries a risk of glucocorticoid-induced adrenal insufficiency. Adrenal insufficiency can cause reluctance to stop glucocorticoid treatment after disease remission as symptoms can resemble PMR/GCA flare. We aimed to determine the prevalence of adrenal insufficiency in prednisolone-treated patients with PMR/GCA. METHODS: We included 47 patients with PMR (n = 37), GCA (n = 1) or both (n = 9), treated with prednisolone for ≥5.4 months, current dose 2.5-10 mg/day. Adrenal function was evaluated using a corticotropin (Synacthen®) stimulation test following 48 h prednisolone pause. Two years' clinical follow-up data are provided. RESULTS: Seven patients (15%) had adrenal insufficiency, 4 (11%) of the 37 patients with PMR alone, and 3 (30%) of the 10 patients with GCA. Corticotropin-stimulated P-cortisol was significantly associated with current prednisolone dose, mean daily dose the last 3 and 6 months before testing, and basal P-cortisol, but not with total dose or treatment duration. Adrenal insufficiency occurred with all current prednisolone doses (2.5-10 mg/day). Five (71%) of the glucocorticoid-insufficient patients could discontinue prednisolone treatment; two of them recovered glucocorticoid function, whereas three still needed hydrocortisone replacement 2 years later. Two patients experienced in total four acute hospital admissions with symptoms of adrenal crises. CONCLUSION: Glucocorticoid-induced adrenal insufficiency occurred in 15% of patients with PMR/GCA. Mean prednisolone dose the last 3 months and basal P-cortisol were the best and simplest predictors of adrenal function. Most of the glucocorticoid-insufficient patients could discontinue prednisolone with appropriate treatment for adrenal insufficiency.

True Chromogranin A concentrations in plasma from patients with small intestinal neuroendocrine tumours.

Objective: The incidence of enteropancreatic neuroendocrine tumours (NET) is increasing. Chromogranin A (CgA) in plasma is a marker in patients suspected of NET tumours. CgA, however, is a precursor protein subjected to cellular processing that challenges quantitation and hence the use of CgA in diagnostics.Materials and methods: CgA concentrations in plasma sampled from 130 well-characterized patients with small intestinal NETs and from 30 healthy subjects were measured with eight commercial CgA kits, an in-house radioimmunoassay (RIA) and a processing-independent assay (PIA). For the evaluation of diagnostic accuracy, we performed regression analyses and plotted receiver-operating characteristic curves (ROC). The specificity was further assessed by size chromatography.Results: Five commercial assays (Thermo-Fisher, DRG Diagnostics, Eurodiagnostica (RIA and ELISA), and Phoenix), displayed a diagnostic accuracy with area under the curve (AUC) values >0.90, whereas three immunoassays (Yanaihara, CisBio RIA, and CisBio ELISA) discriminated poorly between disease stages (AUC: 0.60-0.78). Compared with the in-house assays, however, even the most accurate commercial immunoassay still missed patients with metastatic disease. Chromatography showed non-uniform patterns of large and small CgA fragments in plasma.Conclusion: Available commercial immunoassays measure CgA in plasma with gross variability. Three commercial CgA immunoassays discriminate so poorly between health and disease that they should not be used. The highest diagnostic accuracy was obtained with processing-independent measurement of total CgA concentrations in plasma.

Spectrophotometry of cerebrospinal fluid for xanthochromia is a sensitive and specific test for subarachnoid bleeding but adds little to computed tomography.

Subarachnoid hemorrhage (SAH) is a serious neurological event associated with high morbidity and mortality. Computed tomography of the cerebrum (CTC) is the diagnostic method of choice, but in case of negative CTC but strong suspicion of SAH, lumbar puncture with spectrophotometric analysis of cerebrospinal fluid (CSF) for xanthochromia is performed. We wanted to examine the diagnostic properties of CSF spectrophotometry for xanthochromia testing. We performed a retrospective study of the diagnostic properties of CSF analysis for xanthochromia using spectrophotometry in the diagnosis of SAH. A total of 489 CSF samples were analyzed for xanthochromia, according to international guidelines, from 2009 until 2014 and for 411 of these the patient files were retrieved and examined for final clinical diagnosis and result of CTC. One patient with SAH did not have a positive spectrophotometry report and another patient with SAH had an equivocal report. In four patients did initial CTC not correctly identify SAH. For patients with a negative CTC within six hours of symptom onset spectrophotometry for xanthochromia in the CSF had a diagnostic sensitivity of 100% and a diagnostic specificity of 98.5%. The positive predictive value was 16.7% and the negative predictive value 100%. We conclude that spectrophotometry of CSF for xanthochromia is a sensitive and specific test for diagnosing SAH. However, it seems that an initial CTC identifies almost all patients with SAH. This suggests that in our and similar diagnostic settings, lumbar puncture and testing for xanthochromia might only be relevant in very few cases, if not obsolete.

Gut hormone release after gastric bypass depends on the length of the biliopancreatic limb.

BACKGROUND/OBJECTIVES: Changes in gut hormone secretion are important for the anti-diabetic effects of bariatric surgery. Roux-en-Y gastric bypass (RYGB) with extended biliopancreatic limb (BPL) length may improve the metabolic outcomes when compared to the classical procedure. The purpose of this study was to compare the gut hormone responses to a liquid mixed meal after RYGB with one of two different BPL lengths. SUBJECTS/METHODS: Non-diabetic weight-stable individuals previously submitted to classical RYGB (n = 9; BPL length: 87.8 ± 20.5 cm) or long BPL RYGB (n = 11; BPL length: 200 cm) underwent a liquid mixed-meal tolerance test (MMTT). Blood was sampled at baseline and 15, 30, 45, 60, 90 and 120 min later for measurement of plasma glucose, enteropancreatic hormones and total bile acids (TBA). RESULTS: Plasma glucose excursion curves were similar in the two groups. The long BPL RYGB group displayed significantly higher fasting and post-prandial GLP-1 (t = 0 min, p = 0.01 and t = 45 min, p < 0.05; tAUC: 11,205 ± 3399 vs 7889 ± 1686 pmol/L × min, p = 0.02) and neurotensin (t = 0 min, p = 0.02; t = 45 min, p < 0.05 and t = 60 min, p < 0.01; tAUC: 18,392 ± 7066 vs 11,437 ± 3658 pmol/L × min, p = 0.02) levels, while responses of GIP (t = 15 min, p < 0.01), insulin and C-peptide (t = 30 min, p < 0.001) were lower as compared to classical RYGB. There were no differences in glucagon, PP, PYY and TBA between the groups. CONCLUSIONS: RYGB with a longer BPL results in a distinctive post-prandial hormone profile with augmented GLP-1 and neurotensin responses that could be beneficial for the metabolic outcomes of the surgery.

Biliopancreatic diversion with duodenal switch (BPD-DS) and single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) result in distinct post-prandial hormone profiles.

BACKGROUND/OBJECTIVE: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective bariatric intervention to treat morbid obesity and related disorders. Single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is a new bariatric procedure devised with the purpose of simplifying the complexity of the BPD-DS technique while maintaining its efficacy. However, whether BPD-DS and SADI-S result in similar fasting and post-prandial hormone profiles has not yet been studied. Therefore, the purpose of this study was to assess and compare the hormone response to a standardized mixed meal in subjects operated with BPD-DS or SADI-S. SUBJECTS/METHODS: Subjects submitted to BPD-DS (n = 9) or SADI-S (n = 9) 1.5 years earlier on average, with no past nor current diabetes diagnosis underwent a liquid mixed-meal tolerance test (MMTT) to assess the baseline and post-prandial profile of glucose, enteropancreatic hormones and total bile acids. RESULTS: Fasting glucose, enteropancreatic hormones and total bile acids levels after BPD-DS and SADI-S were similar. After the MMTT, the response of subjects who underwent SADI-S was characterized by higher glucose (t = 30 min: p < 0.05; iAUC: 156.1 ± 46.2 vs. 103.4 ± 35.8 mmol/L × min, p = 0.02), GLP-1 (t = 30 min: p < 0.05; iAUC: 5388 ± 3010 vs. 2959.0 ± 2146 pmol/L × min, p = 0.02), glucagon (t = 30 min: p < 0.05; iAUC: 678.7 ± 295.2 vs. 376.9 ± 215.7 pmol/L × min, p = 0.02), insulin (t = 30 and 45 min: p < 0.05); and C-peptide levels (t = 30 and 45 min: p < 0.05), when compared to BPD-DS. CONCLUSIONS: The post-prandial hormone secretion profile after SADI-S is characterized by increased GLP-1, glucagon and insulin secretion, when compared to BPD-DS, which suggests the existence of different endocrine driven mechanisms leading to weight loss and metabolic improvement after the two procedures.

Investigation of anti-Müllerian hormone concentrations in relation to natural conception rate and time to pregnancy.

The objectives of this study were to investigate whether anti-Müllerian hormone (AMH) concentrations can predict pregnancy rates and time to pregnancy (TTP) in women attempting to conceive naturally/having an unplanned conception, and whether there is a lower AMH threshold compatible with natural conception. This prospective cohort study included 260 women aged 25-42 years in two subcohorts: (A) healthcare workers at Rigshospitalet (2008-2010), and (B) women consulting the Fertility Assessment and Counselling Clinic (2011-2014), Rigshospitalet, Denmark. Pregnancy rates and TTP at 2-year follow-up were stratified into AMH groups: low: < 9.5 pmol/l, intermediate: 9.5-33 pmol/l, high: > 33 pmol/l. Pregnancy rates increased with increasing AMH: 60.1% (low) versus 70.0% (intermediate) versus 78.3% (high) (P = 0.03). The highest pregnancy rate (84.1%) was seen in regular cycling women with high AMH. TTP was reduced in women with high AMH compared with intermediate or low AMH (stepwise trend test P = 0.01). Natural conceptions were observed with AMH concentrations down to 1.2 pmol/l. In conclusion, high AMH, especially in ovulatory women, was associated with higher pregnancy rates. Nonetheless, TTP reflected a large variation in fecundity within similar AMH concentrations and natural conceptions occurred with AMH down to 1.2 pmol/l.

Pediatric reference intervals for general clinical chemistry components - merging of studies from Denmark and Sweden.

BACKGROUND: Reference intervals are crucial tools aiding clinicians when making medical decisions. However, for children such values often are lacking or incomplete. The present study combines data from separate pediatric reference interval studies of Denmark and Sweden in order to increase sample size and to include also pre-school children who were lacking in the Danish study. METHODS: Results from two separate studies including 1988 healthy children and adolescents aged 6 months to 18 years of age were merged and recalculated. Eighteen general clinical chemistry components were measured on Abbott and Roche platforms. To facilitate commutability, the NFKK Reference Serum X was used. RESULTS: Age- and gender-specific pediatric reference intervals were defined by calculating 2.5 and 97.5 percentiles. CONCLUSION: The data generated are primarily applicable to a Nordic population, but could be used by any laboratory if validated for the local patient population.

Rapid gut growth but persistent delay in digestive function in the postnatal period of preterm pigs.

Preterm infants often tolerate full enteral nutrition a few weeks after birth but it is not known how this is related to gut maturation. Using pigs as models, we hypothesized that intestinal structure and digestive function are similar in preterm and term individuals at 3-4 wk after birth and that early enteral nutrition promotes maturation. Preterm or term cesarean-delivered pigs were fed total parenteral nutrition, or partial enteral nutrition [Enteral (Ent), 16-64 ml·kg(-1)·day(-1) of bovine colostrum] for 5 days, followed by full enteral milk feeding until day 26 The intestine was collected for histological and biochemical analyses at days 0, 5, and 26 (n = 8-12 in each of 10 treatment groups). Intestinal weight (relative to body weight) was reduced in preterm pigs at 0-5 days but ENT feeding stimulated the mucosal volume and peptidase activities. Relative to term pigs, mucosal volume remained reduced in preterm pigs until 26 days although plasma glucagon-like peptide 2 (GLP-2) and glucose-dependent insulin-trophic peptide (GIP) levels were increased. Preterm pigs also showed reduced hexose absorptive capacity and brush-border enzyme (sucrase, maltase) activities at 26 days, relative to term pigs. Intestinal structure shows a remarkable growth adaptation in the first week after preterm birth, especially with enteral nutrition, whereas some digestive functions remain immature until at least 3-4 wk. It is important to identify feeding regimens that stimulate intestinal maturation in the postnatal period of preterm infants because some intestinal functions may show long-term developmental delay.

Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms: Twenty-Three Cases Evaluated according to the WHO 2010 Classification.

BACKGROUND/OBJECTIVE: Neuroendocrine neoplasms of the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (pdSOMs) are rare, and knowledge about tumour biology, treatment, survival and prognostic factors is limited. This study aims to describe clinical, pathological and biochemical features as well as treatment and prognosis of pdSOMs. DESIGN: Twenty-three patients with pdSOM (9 duodenal, 12 pancreatic and 2 unknown primary tumours) were identified from our prospective neuroendocrine tumour database, and data according to the study aims were recorded. RESULTS: Among the 9 patients with duodenal SOM, the male/female ratio was 4/5. All males and 1 female had neurofibromatosis type 1. Seven patients had stage 1A/B and 2 had stage 2B disease. The Ki-67 index was 1-5% (median 2%). Plasma somatostatin was elevated in the patients with 2B disease. Of the 14 patients with pancreatic SOM or an unknown primary tumour, the male/female ratio was 2/12. One male had multiple endocrine neoplasia type 1. Five had stage 1A/2B and 9 had stage 4. The Ki-67 index was 1-40% (median 7%). Plasma somatostatin was elevated in 7 patients. Patients reported symptoms related to the somatostatinoma syndrome, but none fulfilled the criteria for a full syndrome. Primary tumour in the pancreas, metastatic disease at diagnosis and higher tumour grade were all associated with significantly poorer survival. CONCLUSION: None of the patients with pdSOM presented with the full somatostatinoma syndrome. Prognostic factors are localisation of the primary tumour, dissemination and tumour grade. A Ki-67 index of 5% may discriminate the course of the disease.