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During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib ( HLA-E, -F and -G ). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal HLA-E*01:06 allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% vs. 4.8%, p = 0.048). The maternal HLA-G 3’-untranslated region UTR4-HLA-G*01:01:01:05 haplotype and the HLA-F*01:03:01 allele were significantly associated with a low anti-HLA I C1q activation (16.7% vs . 57.1%, p = 0.028; 16.7% vs. 50.0%, p = 0.046; respectively). Both HLA‑G and HLA - F*01:03:01 showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain HLA class Ib alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of HLA-E*01:06, HLA-F*01:03 and HLA‑G UTR4 in reducing the risk for allo-immunization.

The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy. We analysed 89 873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21 144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study. In 24 989 (27·8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64 884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19·4% (95% CI 13·2–27·0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identifed seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0·19 per 1000, and no false-negatives were found. The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.

BackgroundElective cesarean section (ECS) can cause moderate to severe pain that often requires opioid administration. To enhance maternal recovery, and promote mother and baby interaction, it is important to reduce postoperative pain and opioid consumption. Various regional anesthesia techniques have been implemented to improve postoperative pain management following ECS. This study aimed to investigate the efficacy of bilateral ultrasound-guided transmuscular quadratus lumborum (TQL) block on reducing postoperative opioid consumption following ECS.MethodsA randomized double-blind trial with concealed allocation was conducted in 72 parturients who received bilateral TQL block with either 30 mL ropivacaine 0.375% or saline. TQL block injectate was deposited in the interfascial plane between the quadratus lumborum and psoas major muscles, posterior to the transversalis fascia. Primary outcome was opioid consumption, which was recorded electronically. Pain scores and time to first opioid request were also evaluated.ResultsOpioid consumption (oral morphine equivalents, OME) was significantly reduced in group ropivacaine (GRO) in the first 24 hours compared with group saline (65 mg OME vs 94 mg OME) with a mean difference of 29 mg OME; 95% CI 3 to 55, p<0.03. Time to first opioid request was significantly prolonged in GRO, p<0.003. Numerical rating scale pain scores were significantly lower in GRO in the first 6 hours after surgery, p<0.03.ConclusionsBilateral TQL block significantly reduced 24 hours’ opioid consumption. Further, we observed significant prolongation in time to first opioid, and significant reduction of pain during the first 6 postoperative hours.

Human leukocyte antigen (HLA)-G, which belongs to a nonclassical class Ib major histocompatibility complex gene family expressed by placental trophoblast cells, plays a central role in establishing tolerance to the semiallogeneic fetus and in placentation. HLA-G exists in different soluble or membrane-bound isoforms. Preeclampsia, a major cause of fetal and maternal morbidity and mortality, has been linked to insufficient placentation and an altered immune response in pregnancy, including altered HLA-G expression. The 14 bp insertion/deletion polymorphism in the 3′ untranslated region of the gene and the isoform profile may affect HLA-G expression. The aim of the current pilot study was to characterize the expression patterns of HLAG mRNA, protein, and isoform profile in uncomplicated term pregnancies and in cases of preeclampsia. Maternal sHLA-G mRNA and protein levels were slightly reduced in preeclampsia. No difference was found for placental blood, and no correlation between peripheral and placental sHLA-G levels was found. We observed no association between neither fetal nor maternal HLA-G 14 bp insertion/deletion genotypes and preeclampsia, nor a significant difference in isoform profiles. However, in HLA-G 14 bp insertion/deletion heterozygous placental samples, we observed abundant HLA-G1 14 bp insertion allele expression in the term placentae, which is contrary to previous findings in first trimester trophoblast. Increased HLA-G1 14 bp insertion allele expression in the placenta was associated with reduced levels of placental sHLA-G and an altered isoform profile with increased relative levels of HLA-G1 and -G5 and reduced levels of HLA-G3. The results indicate that an allelic shift in heterozygous individuals could represent a novel regulatory pathway. Summary sentence Detailed studies of HLA-G isoform and allele expression in preeclampsia and healthy pregnancies reveal a change in allelic dominance during pregnancy and may support reduced levels of soluble HLA-G in maternal blood in preeclampsia.

Aims The present study had two aims: (i) compare echocardiographic parameters in COVID‐19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID‐19 related death. Methods and results In this prospective multicentre cohort study, 214 consecutive hospitalized COVID‐19 patients underwent an echocardiographic examination (by pre‐determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID‐19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow‐up (median: 40 days), 25 COVID‐19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07–1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07–1.35], P = 0.002, per 1% decrease) were significantly associated with COVID‐19‐related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease. Conclusions RV and LV function are significantly impaired in hospitalized COVID‐19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID‐19‐related death.

Background Four published case reports have proposed Lyme neuroborreliosis (LNB) as a trigger for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. In this study, we examined the prevalence of anti-NMDAR antibodies in a well-characterized cohort of patients with LNB. Methods In this retrospective cohort study, archived cerebrospinal fluid (CSF) samples from patients diagnosed with LNB between 2001 and 2012 were analyzed for anti-NMDAR IgG using a standard commercial cell-based assay. LNB diagnosis followed the European Federation of Neurological Societies guidelines. To identify potential later development of anti-NMDAR encephalitis, an infectious disease specialist systematically reviewed medical records in 2021, and the national reference center for neural autoantibody testing verified testing history in 2025. Results We included 82 patients with a median age of 52 years (interquartile range [IQR]: 34–63); 55% were male. Median symptom duration before diagnosis was 21 days (IQR: 7–45). The most frequent symptoms were cranial nerve palsy (51%) and radiating pain (50%). Among 70 patients with available CSF data, limited by access to laboratory records, the median CSF leukocyte count was 124 × 10 6 cells/L (IQR: 61–236). None of the 82 CSF samples tested positive for anti-NMDAR antibodies, resulting in an estimated prevalence of 0% (95% CI: 0.0–4.4). No patients were clinically suspected of autoimmune encephalitis or tested for it. Conclusion Anti-NMDAR antibodies were not detected in the CSF of LNB patients, suggesting their presence is rare in this population at diagnosis. Although the sample size may limit statistical power, the absence of later clinical suspicion or testing supports the hypothesis that LNB is an uncommon trigger for anti-NMDAR encephalitis.

Background Antiretroviral therapy (ART) in people with HIV (PWH) can lead to weight gain, but the effects of nucleoside reverse transcriptase inhibitors such as abacavir (ABC) are not well understood. In this study, we investigated whether discontinuing ABC would mitigate weight changes and metabolic complications in PWH. Methods In a randomized controlled trial including PWH on dolutegravir, ABC, and lamivudine (DTG/ABC/3TC), participants were randomized 2:1 to either switch to DTG/3TC or continue DTG/ABC/3TC. Data was collected at baseline, week 24, and week 48. This study was powered to detect a difference of 2 kg in weight between groups. Secondary outcomes included body composition, fat and muscle distribution, and metabolic parameters. Weight and metabolic changes were analyzed by linear mixed modeling. Results Eighty-one participants were randomized. Switching from DTG/ABC/3TC to DTG/3TC was not associated with a significant change in weight at 48 weeks in the intention to treat (ITT) analysis (mean difference − 0.5 kg, 95% confidence interval (CI): -2.5 to 1.5, p  = 0.599) or the modified ITT, (-0.1 kg, 95% CI: -1.7 to 1.5, p  = 0.914). In the ITT analysis, the DTG/3TC group gained 0.4 kg ± 5.1 SD ( p  = 0.589) compared to 0.9 kg ± 2.3 SD ( p  = 0.054) in the DTG/ABC/3TC group, while in the modified ITT, the changes were 0.9 ± 3.2 kg ( p  = 0.054) and 0.9 ± 3.6 kg ( p  = 0.071), respectively. The were no differences between groups in secondary outcomes. Conclusion Continuing or discontinuing abacavir for 48 weeks was associated with modest gains in weight that did not differ between groups. Similarly, fat distribution, or metabolic parameters were comparable between groups.

Lowering glucose levels is a complex task for patients with type 1 diabetes, and they often lack contact with health care professionals. Intermittently scanned continuous glucose monitoring (isCGM) has the potential to aid them with blood glucose management at home. The aim of this study was to investigate the long-term effect of isCGM on HbA.sub.1c in type 1 diabetes patients with poor glycaemic control in a region-wide real-world setting. All patients with type 1 diabetes receiving an isCGM due to poor glycaemic control ([greater than or equal to]70 mmol/mol [[greater than or equal to]8.6%]) in the period of 2020-21 in Region North Denmark (\"T1D-CGM\") were compared with all type 1 diabetes patients without isCGM (\"T1D-NOCGM\") in the same period. A multiple linear regression model adjusted for age, sex, diabetes duration and use of continuous subcutaneous insulin infusion was constructed to estimate the difference in change from baseline HbA.sub.1c between the two groups and within subgroups of T1D-CGM. A total of 2,527 patients (T1D-CGM: 897; T1D-NOCGM: 1,630) were included in the study. The estimated adjusted difference in change from baseline HbA.sub.1c between T1D-CGM vs T1D-NOCGM was -5.68 mmol/mol (95% CI: (-6.69 to -4.67 mmol/mol; p<0.0001)). Older patients using isCGM dropped less in HbA.sub.1c. Our results indicate that patients with type 1 diabetes in poor glycaemic control from Region North Denmark in general benefit from using isCGM with a sustained 24-month improvement in HbA.sub.1c, but the effect on HbA.sub.1c may be less pronounced for older patients.