Is the Perinatal Outcome of Placental Abruption Modified by Clinical Presentation?

Objective. The purpose of this study was to elucidate the impact of the clinical presentation on perinatal outcome in placental abruption. Study Design. A retrospective study was performed in 97 placental abruptions. Placental abruptions were classified according to clinical presentation: pregnancy-induced hypertension (HT, n = 22), threatened premature labor and/or premature rupture of membranes (TPL/ROM, n = 35), clinically low risk (LR, n = 27), and others (n = 13). Perinatal outcomes were compared among the HT, TPL/ROM, and LR groups. Results. The HT had significantly higher incidence of IUGR, IFUD, and low fibrinogen. The TPL/ROM had less severe disease. However, the LR had significantly higher incidence of IUFD, low UA pH < 7.1, low Apgar score of <7 at 5 min, and low fibrinogen. Conclusion. Disease severity in placental abruption is likely to depend on the clinical presentation

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Circadian Variation in the Onset of Placental Abruption

Objective. To determine circadian variation in the onset of placental abruption. Methods. A retrospective study involving 115 placental abruptions, divided into four subgroups based on initial symptoms comprising abdominal pain, vaginal bleeding, both abdominal pain and bleeding, or other symptoms. The time of the initial symptom was considered the disease onset. We analyzed the frequency of disease onset and adverse perinatal outcome including perinatal death relative to the daily four 6-hour intervals. Results. Abdominal pain displayed significant circadian variation regarding the period of onset with higher levels from 0:00 AM to 6:00 AM (65%) compared with 0:00 PM to 6:00 PM (24%, p<0.01). Vaginal bleeding did not display significant circadian variation (p=0.45). Adverse perinatal outcome showed significant circadian variation with a higher occurrence of perinatal death from 0:00 AM to 6:00 AM (35%) compared with 0:00 PM to 6:00 PM (0%, p<0.01). After adjustment using variables of abdominal pain and time period, both variables significantly affected perinatal death (odds ratio: 13.0 and 2.2, resp.). The risk of adverse perinatal outcome increased significantly when abdominal pain occurred, except for the period 0:00 PM to 6:00 PM (OR, 9.5). Conclusion. Placental abruption beginning with abdominal pain has circadian variation

Maternal Morbidity in Women with Placenta Previa Managed with Prediction of Morbidly Adherent Placenta by Ultrasonography

Objective. To determine maternal morbidity in women with placenta previa managed with prediction of morbidly adherent placenta (MAP) by ultrasonography. Methods. A retrospective cohort study was undertaken comprising forty-one women who had placenta previa with or without risk factors for MAP. Women who had all three findings (bladder line interruption, placental lacunae, and absence of the retroplacental clear zone) were regarded as high suspicion for MAP and underwent cesarean section followed by hysterectomy. We attempted placental removal for women having two findings or less. Results. Among 28 women with risk, nine with high suspicion underwent hysterectomy and were diagnosed with MAP. Three of 19 women with two findings or less eventually underwent hysterectomy and were diagnosed with MAP. The sensitivity and positive predictive value for the detection of MAP were 64% and 100%. The pathological severity of MAP was significantly correlated with the cumulative number of findings. There were no cases of MAP among 13 women without risk. There was no difference of blood loss between women with high suspicion and those without risk (2186±1438 ml versus 1656±848 ml, resp.; p=0.34). Conclusion. Management with prediction of MAP by ultrasonography is useful for obtaining permissible morbidity

Plasmapheresis for the Treatment of Anti-M Alloimmunization in Pregnancy

Intrauterine transfusion is the standard antenatal treatment for a fetus with severe anemia. Plasmapheresis is an alternative treatment for cases with a history of severe hemolytic disease of the fetus and newborns at less than 20 weeks of gestation. There is only one previous report of plasmapheresis for the anti-M alloimmunization in pregnancy, and we report here on the successful treatment of plasmapheresis for anti-M alloimmunization. A woman with a history of intrauterine fetal death at 24 weeks of gestation due to severe fetal anemia caused by anti-M alloimmunization received plasmapheresis once or twice a week from 14 weeks of gestation onward. An intrauterine blood transfusion was conducted at 28 weeks, and a cesarean section was performed at 31 weeks. The infant had anemia and jaundice but was discharged at day 46. Plasmapheresis may delay the development of fetal anemia and reduce the risk of early and repeat intrauterine transfusion in cases of anti-M alloimmunization in pregnancy

Aberrant DNA methylation is associated with a poor outcome in Juvenile myelomonocytic leukemia

Juvenile myelomonocytic leukemia (JMML), an overlap of myelodysplastic/myeloproliferative neoplasm, is an intractable pediatric myeloid neoplasm. Epigenetic regulation of transcription, particularly by CpG methylation, plays an important role in tumor progression, mainly by repressing tumor-suppressor genes. To clarify the clinical importance of aberrant DNA methylation, we studied the hypermethylation status of 16 target genes in the genomes of 92 patients with JMML by bisulfite conversion and the pryosequencing technique. Among 16 candidate genes, BMP4, CALCA, CDKN2A, and RARB exhibited significant hypermethylation in 72% (67/92) of patients. Based on the number of hypermethylated genes, patients were stratified into three cohorts based on an aberrant methylation score (AMS) of 0, 1-2, or 3-4. In the AMS 0 cohort, the 5-year overall survival (OS) and transplantation-free survival (TFS) were good (69% and 76%, respectively). In the AMS 1-2 cohort, the 5-year OS was comparable to that in the AMS 0 cohort (68%), whereas TFS was poor (6%). In the AMS 3-4 cohort, 5-year OS and TFS were markedly low (8% and 0%, respectively). Epigenetic analysis provides helpful information for clinicians to select treatment strategies for patients with JMML. For patients with AMS 3-4 in whom hematopoietic stem cell transplantation does not improve the prognosis, alternative therapies, including DNA methyltransferase inhibitors and new molecular-targeting agents, should be established as treatment options