Regulatory T cells in the peripheral blood of women with gestational diabetes: a systematic review and meta-analysis

BackgroundGestational diabetes (GDM) affects approximately 14% of pregnancies globally and is associated with short- and long-term complications for both the mother and child. In addition, GDM has been linked to chronic low-grade inflammation with recent research indicating a potential immune dysregulation in pathophysiology and a disparity in regulatory T cells.ObjectiveThis systematic review and meta-analysis aimed to determine whether there is an association between GDM and the level of Tregs in the peripheral blood.MethodsLiterature searches were conducted in PubMed, Embase, and Ovid between the 7th and 14th of February 2022. The inclusion criteria were any original studies published in the English language, measuring differentiated Tregs in women with GDM compared with glucose-tolerant pregnant women. Meta-analysis was performed between comparable Treg markers. Statistical tests were used to quantify heterogeneity: τ2, χ2, and I2. Study quality was assessed using a modified version of the Newcastle-Ottawa scale.ResultsThe search yielded 223 results: eight studies were included in the review and seven in the meta-analysis (GDM = 228, control = 286). Analysis of Tregs across all trimesters showed significantly lower Treg numbers in women with GDM (SMD, −0.76; 95% CI, −1.37, −0.15; I2 = 90%). This was reflected in the analysis by specific Treg markers (SMD −0.55; 95% CI, −1.04, −0.07; I2 = 83%; third trimester, five studies). Non-significant differences were found within subgroups (differentiated by CD4+FoxP3+, CD4+CD127−, and CD4+CD127−FoxP3) of both analyses.ConclusionGDM is associated with lower Treg numbers in the peripheral maternal blood. In early pregnancy, there is clinical potential to use Treg levels as a predictive tool for the subsequent development of GDM. There is also a potential therapeutic intervention to prevent the development of GDM by increasing Treg populations. However, the precise mechanism by which Tregs mediate GDM remains unclear.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42022309796

Progressive multifocal leukoencephalopathy in the context of newer therapies in hematology and review of new treatment strategies

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system (CNS) caused by the reactivation of JC polyomavirus in the CNS. We present a case of a 54-year-old man with follicular lymphoma diagnosed with PML after being treated with anti-CD20 monoclonal antibody-based regimens for several years. Due to the lack of effective treatment choices for PML, the patient was treated with nivolumab, based on recent reports, but succumbed to his disease a few months after diagnosis. In this paper, we focus on reviewing the literature of PML cases correlated with newer agents used in hematology, possible factors affecting disease prognosis, as well as the available data on upcoming therapeutic options for patients with PML. Though newer promising treatments such as anti-PD1 monoclonal antibodies arise, a definitive treatment option is yet to be found. Vigilance, early detection, and prompt intervention play a crucial role in the prognosis of PML in patients with hematological malignancies

Isolation and freezing of human peripheral blood mononuclear cells from pregnant patients

To analyze immune cell populations accurately, a large number of Peripheral Blood Mononuclear Cells (PBMCs) must be obtained from blood samples. Traditional manual isolation and SepMate(TM) isolation of PBMCs consistently yield blood-stained plasma layers and overall low numbers of CD4+ and CD8+ cells. Here, we describe an optimized protocol, using PBS with EDTA to increase PBMC yield from pregnant patients. This protocol enables analysis of CD4+, CD8+, and Regulatory T Cells and is potentially applicable to any immune cell population. For complete details on the use and execution of this protocol, please refer to the SepMateTM website https://www.stemcell.com/products/brands/SepMateTM-pbmc-isolation.html

Suspected twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy: a case report

BACKGROUND: Twin anemia polycythemia sequence is a rare complication in monochorionic twin pregnancy. CASE PRESENTATION: We describe a case of dichorionic twin pregnancy presenting with suspected twin anemia polycythemia sequence. A 31-year-old White female, on her third pregnancy, had a routine ultrasound scan at 12 weeks gestation, which demonstrated a dichorionic twin pregnancy with one placenta located in the anterior wall and the other in the posterior wall of the uterus. At 21 weeks, a scan demonstrated a 24% growth discordance between the two fetuses with normal Doppler studies and amniotic fluid. At 27 weeks, one twin showed signs of anemia and the other polycythemia; the fetal middle cerebral artery peak systolic velocity was high in the anemic fetus and low in the polycythemic twin (1.8 and 0.5 multiples of the median). An intrauterine blood transfusion was carried out and this increased the fetal hemoglobin concentration in the anemic twin from 3.5 to 12.5 g/dL. At 29 weeks, delivery by cesarean section was carried out because of evidence from middle cerebral artery peak systolic velocity of recurrence of anemia in one twin and worsening polycythemia in the co-twin; at birth the hemoglobin concentrations were 5.6 and 24.9 g/dL, respectively. Histopathological examination confirmed dichorionicity with no communicating vessels between the two placentas. CONCLUSIONS: This is the first case of twin anemia polycythemia sequence in a dichorionic, diamniotic twin pregnancy where intrauterine blood transfusion was used to prolong the pregnancy by almost 2 weeks in a “twin anemia polycythemia sequence-like” setting

Enhancing health and eHealth literacy among nurses working with older people during COVID-19 pandemic: A multi-center e-Delphi study in five countries

Background: Nurses’ health literacy (HL) and ehealth literacy (eHL) knowledge and skills are crucial for patient care. There is evidence that skills and knowledge on how HL and eHL can facilitate the provision of care, is low among nurses. Especially in the care of older adults with an increased risk of falls and infections, or poor adherence to pharmacotherapy, nurses could increase patient safety by assessing and supporting older people’ HL and eHL. This study aims to present the findings of an e-Delphi survey, which was implemented within the framework of the development of a course focusing on the enhancement of HL and eHL assessment and intervention competencies for nurses. Method: A modified e-Delphi study was conducted in five countries from September 2020 to January 2021. Initially, a 19-item questionnaire on HL and eHL skills and competencies was developed by the research team based on literature review. Twenty experts from five countries (Cyprus, Czech Republic, Greece, Lithuania, Poland) participated in two e-Delphi rounds. The research team met to reach consensus on the final version of the modules. Results: Four modules were derived from the Delphi survey: 1) Introduction to HL and eHL 2) Communication skills in practice 3) eHealth challenges: Feasibility and readability issues, and 4) HL/eHL and patient safety. Conclusions: Raising awareness on HL and eHL skills in nurses and nursing students is considered a priority, especially during the COVID-19 era. The common effort among five academic institutions to develop an HL and eHL course targeting nurses and nursing students is considered an important step towards this direction

Regulatory T Cells in Pregnancy Adverse Outcomes:A Systematic Review and Meta-Analysis

BackgroundSeveral studies report the role of Regulatory T-cells (Tregs) in the pathophysiology of pregnancy adverse outcomes.ObjectiveThe aim of this systematic review and meta-analysis was to determine whether there is an association between regulatory T cell levels and pregnancy adverse outcomes (PAOs), including pre-eclampsia and preterm birth (PTB).MethodLiterature searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases. Inclusion criteria were original articles (clinical trials, case-control studies and cohort studies) comparing Tregs, sampled from the decidua or maternal blood, in healthy pregnant women versus women with pre-eclampsia or PTB. The outcome was standardised mean difference (SMD) in Treg numbers. The tau-squared (Tau²), inconsistency index (I²), and chi-squared (χ²) test quantified heterogeneity among different studies. Analyses were performed in RevMan software V.5.4.0 for Mac using a random-effects model with outcome data reported with 95% confidence intervals (CI). This study was prospectively registered with PROSPERO (CRD42020205469). PRISMA guidelines were followed.ResultsFrom 4,085 unique studies identified, 36 were included in qualitative synthesis, and 34 were included in quantitative synthesis (meta-analysis). In total, there were 1,783 participants in these studies: healthy controls=964, pre-eclampsia=759, PTB=60. Thirty-two studies compared Tregs in healthy pregnant women and women with pre-eclampsia, and 30 of these sampled Tregs from peripheral blood showing significantly higher Treg numbers in healthy pregnancies (SMD; 1.46; 95% CI, 1.03–1.88; I²=92%). Four studies sampled Tregs from the maternal decidua showing higher Tregs in healthy pregnancies (SMD, 0.76; 95% CI, -0.13–1.65; I²=84%). No difference was found in the number of Tregs between early versus late pre-eclampsia (SMD,-1.17; 95% CI, -2.79–0.44; I²=94%). For PTB, two studies compared Tregs sampled from the peripheral blood with a tendency for higher Tregs in healthy pregnancies but this did not reach significance (SMD, 2.18; 95% CI, -1.34–5.70; I²=96%). Subcohort analysis using Treg analysis (flow cytometry vs. qPCR vs. immunofluorescence tissue staining) showed similar associations.ConclusionLower Tregs in pregnancy, sampled from the maternal peripheral blood, are associated with pre-eclampsia. There is a need for further studies to confirm a relationship between low Tregs and PTB. As the precise mechanisms by which Tregs may mediate pre-eclampsia and PTB remain unclear, further fundamental research is necessary to elucidate the underlying processes and highlight the causative link.Systematic Review RegistrationPROSPERO, identifier CRD42020205469