Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan

Komatsu R., Mimura K., Matsuyama T., et al. Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan. Journal of Obstetrics and Gynaecology Research , (2024); https://doi.org/10.1111/jog.15949.Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates

Cyclin dependent kinase inhibitorによる神経前駆細胞の分化誘導と脳形成

大脳皮質は知覚,認知,思考等の高次機能を担う中枢である.哺乳類では大脳皮質は6層構造をなし,それぞれの層では機能的,形態的に類似した細胞集団が異なる領域からの投射をやり取りしている.神経細胞およびグリア細胞は,胎生期から生後にかけて神経前駆細胞(Neural progenitor cell,NPC)から分裂し産生される.NPCは時期に応じて神経細胞,続いてグリア細胞へ分化し,最終的な脳の構造が完成する.NPCから分化する細胞運命の決定には,細胞分裂を中止して分化を始める機構が必要であり,その中でもCyclin dependent kinase inhibitors(CKIs)の働きが注目されている.今回我々はこのCKIsのひとつであるp18遺伝子を用いて胎児マウス脳の発生に与える影響を解析した.方法としては胎生13～17日目(E13-17)のマウス胎児脳にp18遺伝子を子宮内エレクトロポレーション法によって強制発現させ,その後に脳組織内での分布を観察した.またCre-LoxP を用いた蛍光蛋白発現システムで個々の細胞形態の立体再構築を行った.その結果,p18遺伝子発現群はコントロール群に比べて多く脳室面側に留まり,特にE14, 15において顕著に認められた.更に遺伝子導入した細胞において分化後の形態を観察したところ,生後脳においてp18遺伝子発現群ではアストロサイトの形態をした細胞が増えており,免疫組織学的染色からもこれらの細胞がアストロサイトであることが示唆された.この細胞はE13～E17いずれの時期においても増加していたが,特にE14,15で顕著に認めたことから,この時期にニューロンの分化からアストロサイトの分化に切り替わる何らかのメカニズムが存在していると考えられた.今回の研究によってNPCがニューロンへの分化からアストロサイトへの分化に切り替わるメカニズムにCKIsが関与している可能性が示唆された.アストロサイトはグルタミントランスポータの発現により,二次的脳損傷から神経細胞を保護しており,その発生が解明されることで低酸素性虚血性脳症の治療への応用も期待される.The cerebral cortex plays a central role in high-level functions such as thinking, perception, and cognition. In mammals, the cerebral cortex has a six-layered structure, and each layer contains cells with similar functions and shapes that exchange signals from different regions of the brain. Neurons and glial cells are produced by differentiation from neural progenitor cells(NPC)from the embryonic stage up to the postnatal stage. NPCs are differentiated into neurons at the embryonic stage, and switch into glial cells at birth, before the structure of the brain is mature. Some molecules have been proposed to determine the cell fate of NPCs by stopping cell division and initiating differentiation. Cyclindependent kinase inhibitors(CKIs)are considered to be important molecular factors in this process. Here we used a CKI, the p18 gene, and analyzed its effect on the formation of the fetal mouse brain. For this purpose, we expressed the p18 gene in the mouse fetal brain at embryonic day 13 to day 17(E13-17), and observed the distribution of the electroporated cells in the cortical tissue. Furthermore, we performed three-dimensional reconstruction of the individual cellular morphology by using the Cre-LoxP fluorescent protein expression system. As a result, the p18-gene expressing cells remained in the ventricular zone more than the control cells. The difference was particularly remarkable at E14 and E15. Importantly, we observed a differentiated cell shape in electroporated cells, and found that the proportion of astrocyte-like cells was greatly increased in the p18 gene-expressing group compared to the control group. We confirmed that these cells were indeed astrocytes with immunohistochemical staining. The number of such astrocyte-like cells increased at any time of electroporation from E13 to E17, especially at E14 and E15. Therefore, we propose that there might be some mechanisms that control the switch from neurons to astrocytes at this stage of development. In conclusion, our study suggests that CKIs are involved in the differentiation program of NPCs from neurons to astrocytes. Astrocytes are known to protect neurons from secondary brain damage by the expression of glutamine transporter. Therefore, elucidating the mechanism of their generation is expected to have applications for the treatment of hypoxic-ischemic encephalopathy in the future

The Amnioscope Strikes Back as a Useful Device for Pinhole Amniotomy in the Management of Polyhydramnios

Polyhydramnios is associated with many serious maternal complications such as placental abruption or cord prolapse at rupture of membranes, uterine dysfunction at delivery, and postpartum hemorrhage. When considering uterine dysfunction caused by overstretched uterine muscles, active artificial amniotomy for more efficient labor seems to be a preferred obstetric management, but the potential adverse complications make obstetricians hesitate to perform this procedure. In such a challenging situation, a new strategy is required. We recently performed pinhole artificial amniotomy using an amnioscope in four women with polyhydramnios, not only to accelerate of labor but also to more slowly and safely reduce amniotic fluid volume. We had no complications using this procedure, and all women were able to have a vaginal delivery without postpartum hemorrhage and neonatal asphyxia. Pinhole artificial amniotomy using an amnioscope may be more convenient and safer than conventional artificial amniotomy. The significance of the amnioscope has been practically nil in modern obstetric management. In this pilot clinical study, we identified a new value for the amnioscope as a promising device for safer amniotomy in women with polyhydramnios

Preeclampsia: Maternal Systemic Vascular Disorder Caused by Generalized Endothelial Dysfunction Due to Placental Antiangiogenic Factors

Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and perinatal morbidity and mortality. Maternal endothelial dysfunction caused by placental factors has long been accepted with respect to the pathophysiology of preeclampsia. Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunction. This review summarizes the recent advances in understanding the molecular mechanisms of endothelial dysfunction caused by placental antiangiogenic factors, and the novel clinical strategies based on these discoveries

Differential diagnosis of bilateral ovarian masses during pregnancy, and their hormonal effect

Rapidly enlarging bilateral ovarian cystic masses can be confused with malignant entities. When this happens during pregnancy, benign transient reactivity can present a similar clinical course. Here we describe a 33-year-old woman with hyperreactio luteinalis or multiple gestational theca lutein cysts whose ovaries drastically changed in size peripartum, with concordant changes in human chorionic gonadotropin, thyroid function, and testosterone levels. Management was conservative and the cystic masses spontaneously remitted postpartum. Present work suggested that evaluating the character of the cysts by magnetic resonance imaging and serial assessments of their size and the patient’s hormonal levels may assist in diagnosis. Conservative management could be successfully applied in a carefully chosen subset of patients to avoid unnecessary invasive procedures

Pure Primary Ovarian Squamous Cell Carcinoma Perforating the Rectum

Rectal perforation is uncommon in ovarian cancer, even in advanced stages. Pure primary ovarian squamous cell carcinoma is a very rare subtype of ovarian cancer and has not been reported to cause rectal perforation. A 50-year-old woman presented with rectal bleeding. Rectosigmoidoscopy suggested perforation of a pelvic tumor into the rectum. Abdominopelvic magnetic resonance imaging revealed a 9 cm heterogeneous mass in the pouch of Douglas. We performed complete cytoreduction, including an en-bloc resection of the tumor and rectosigmoid colon. Histopathology showed squamous cell carcinoma of the left ovary penetrating the rectal wall. A common symptom of rectal bleeding was caused by a very rare entity of ovarian cancer penetrating the rectal wall, but thorough evaluation led to its accurate diagnosis and appropriate treatment