HELLP Syndrome at 20 Gestational Weeks Managed Using the Mississippi Protocol: A Case Report.

Hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) syndrome is one of the most severe complications of hypertensive disorders of pregnancy. HELLP syndrome occurring before 22 gestational weeks (GWs) is extremely rare, and patients prevalently exhibit underlying maternal diseases or fetal abnormalities. Here, we report the case of a pregnant woman who had HELLP syndrome at 20 GWs without any obvious underlying maternal diseases or fetal abnormalities. A 38-year-old pregnant woman was referred to Kobe University Hospital from another hospital at 19 + 5/7 GWs for hypertension, proteinuria, generalized edema, and fetal growth restriction. She was diagnosed with partial HELLP syndrome according to the Mississippi classification at 20 + 2/7 GWs. The patient was managed following the Mississippi protocol, including intravenous dexamethasone, magnesium sulfate, and antihypertensive drugs. She received intensive blood pressure and laboratory data monitoring using an arterial line and additional treatments, including platelet transfusion, intravenous haptoglobin infusion, and human atrial natriuretic peptide. The pregnancy ended in an induced delivery at 20 + 3/7 GWs, and she was discharged without complications 10 days postnatal. We performed laboratory tests for diagnosing underlying diseases but identified no obvious underlying diseases. This report indicates that early and intensive treatment of patients with HELLP syndrome occurring before 22 GWs according to the Mississippi protocol may enable clinicians to complete pregnancy termination without maternal complications and provide useful information to clinical practitioners in perinatal medicine.

Toxoplasma gondii IgG avidity for the diagnosis of primary infection in pregnant women: Comparison between chemiluminescent microparticle immunoassay and enzyme-linked immunosorbent assay.

INTRODUCTION: This study evaluated whether IgG avidity measured by chemiluminescent microparticle immunoassay (CMIA) compared with enzyme-linked immunosorbent assay (ELISA) was useful to detect primary T. gondii infection during pregnancy and to estimate the risk for congenital T. gondii infection. METHODS: One hundred six women with positive tests for T. gondii IgG and T. gondii IgM, comprising 21 women (19.8%) with low (<30%), 6 (5.7%) with borderline (30%-35%), and 79 (74.5%) with high (>35%) IgG avidity measured by ELISA were selected. Their stored sera were used for T. gondii IgG avidity measurements by CMIA. RESULTS: In CMIA, 72 (67.9%) women had low (<50%), 12 (11.3%) had borderline (50%-59.9%), and 22 (20.8%) had high (≥60%) IgG avidity. The ratio of low T. gondii IgG avidity index in CMIA was more than three-fold than that in ELISA. Eighteen (85.7%) of 21 women with ELISA low avidity also had CMIA low avidity, and 26 (96.3%) of 27 women with ELISA low or borderline avidity corresponded to CMIA low or borderline avidity, whereas 21 (26.6%) of 79 women with ELISA high avidity were diagnosed with CMIA low avidity. All three cases with congenital T. gondii infection showed coincidentally low IgG avidity in both methods. A positive correlation in IgG avidity indices was found between of ELISA and CMIA. CONCLUSIONS: CMIA for T. gondii avidity measurements compared with ELISA was clinically useful to detect pregnant women at a high risk of developing congenital T. gondii infection.

Advantages of sensor-augmented insulin pump therapy for pregnant women with type 1 diabetes mellitus.

AIMS/INTRODUCTION: To evaluate the efficacy of sensor-augmented pump (SAP) for improving obstetric and neonatal outcomes among pregnant women with type 1 diabetes mellitus by comparing it with continuous subcutaneous insulin infusion plus self-monitoring of blood glucose (continuous subcutaneous insulin infusion [CSII]/SMBG). MATERIALS AND METHODS: This retrospective cohort study included 40 cases of pregnancy complicated by type 1 diabetes mellitus treated with SAP (SAP group), and 29 cases of pregnancy complicated by type 1 diabetes mellitus treated with CSII/SMBG (CSII/SMBG group). The obstetric and neonatal outcomes were compared between the two groups. RESULTS: The median of the glycoalbumin levels in the first (18.8% vs 20.9%; P < 0.05) and second (15.4% vs 18.0%; P < 0.05) trimesters, the hemoglobin A1c levels in the peripartum period (6.1% vs 6.5%; P < 0.05) and the standard deviation score of birthweights (0.36 vs 1.52; P < 0.05) were significantly lower in the SAP group than in the CSII/SMBG group. The incidence rate of large for gestational age newborns was significantly lower in the SAP group than in the CSII/SMBG group (27.5% vs 65.5%; P < 0.05). No significant differences in the incidence rates of hypertensive disorders of pregnancy, small for gestational age, respiratory distress syndrome, neonatal hypoglycemia, hypervolemia and hyperbilirubinemia were observed between the groups. CONCLUSION: The present study showed that SAP therapy is more effective in preventing large for gestational age newborns in pregnant women with type 1 diabetes mellitus than CSII/SMBG.

Two pregnant women with immune-mediated thrombotic thrombocytopenic purpura: A case report.

Thrombotic thrombocytopenic purpura (TTP) during pregnancy is life-threatening. We encountered two pregnant women with immune-mediated TTP (iTTP). A 40-year-old primigravida woman was referred at 19 gestational weeks (GWs) owing to iTTP. She received plasma exchange (PE) and steroid therapies and delivered a live infant at 27 GWs by cesarean delivery. A 29-year-old primigravida woman was referred owing to intrauterine fetal death and thrombocytopenia at 20 GWs. She was diagnosed with iTTP and received PE therapy. She required additional PE and steroid therapies owing to relapse. Before her second pregnancy, she received prednisolone and hydroxychloroquine according to the therapy for systemic lupus erythematosus (SLE). She had induced labor at 37 GWs owing to decrease plasma level of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity. Close monitoring of plasma ADAMTS13 activity level and treatments for underlying SLE may prevent iTTP relapse and lead to a good prognosis.

Leukemic-phase mucosa-associated lymphoid tissue lymphoma.

A 78-year-old man presenting with leukocytosis was admitted to our hospital. The patient was asymptomatic and showed no lymphadenopathy. Peripheral blood flow cytometry revealed a leukemic-phase B-cell lymphoma with medium-to-large abnormal cells with reticulum. Positron emission tomography/computed tomography revealed abnormal uptake in the right orbit, bone marrow, and spleen. We performed immunological staining and fluorescence in situ hybridization on tissues extracted from the right orbit and bone marrow, which led to the diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. Polymerase chain reaction analysis of immunoglobulin heavy chain rearrangements in the right orbital mass and bone marrow suggested that they were identical clones. Based on these collective findings, the diagnosis of leukemic-phase MALT lymphoma was confirmed, with sites of involvement including the bone marrow, peripheral blood, right orbit, and spleen. This is a highly rare case of leukemic MALT lymphoma.

Rapid reduction of adenomyosis coexisting with leiomyoma volume during treatment with Relugolix.

OBJECTIVE: This study elucidated the efficacy of Relugolix (REL) on the reduction of uterine volume and clinical symptoms for the treatment of adenomyosis. METHODS: We conducted a retrospective cohort study of patients who received REL (40 mg for about 20 weeks) and who underwent a hysterectomy for adenomyosis or fibroids. We divided patients into two groups: adenomyosis coexisting with fibroids (Group A) and fibroids only (Group B); the groups were determined by a postoperative pathological examination. The primary end points were the percent reduction in uterine volume, adenomyotic lesion, and the largest fibroid volume at week 16. The secondary end points were the rate of amenorrhea, pelvic pain, and anemia at week 12. RESULTS: A total of 56 patients participated in the current study: 20 in Group A and 36 in Group B. Regarding the largest fibroid volume, there was no significant difference between the two groups. Uterine volume after REL treatment was significantly decreased in Group A (43%), as compared to Group B (27%) (p = .00972), In Group A, adenomyotic lesion was decreased by 61%. Irrespective of the group, adenomyosis showed a significant reduction compared to uterine fibroids (p < .001). There was no statistically significant difference in the mitigation of symptoms (amenorrhea, pelvic pain, and anemia) between the two groups. CONCLUSIONS: REL is more effective in reducing adenomyotic lesion than uterine fibroids and in relieving symptoms (amenorrhea, pelvic pain, and anemia). It can be expected that REL will also be used as a preoperative treatment for adenomyosis.

Uterine rupture in intramural ectopic pregnancy: A case report.

Intramural pregnancy is a rare form of ectopic pregnancy. It is defined by a gestation within the uterine wall, completely surrounded by myometrium and separated from the uterine cavity and the fallopian tube. We report a rare case of intramural ectopic pregnancy. If a patient has a history of intrauterine surgery or myomectomy, the possibility of intramural pregnancy, although rare, should not be ruled out.

Fetal Ultrasound and Magnetic Resonance Imaging Abnormalities in Congenital Cytomegalovirus Infection Associated with and without Fetal Growth Restriction.

Congenital cytomegalovirus infection (cCMV) can cause fetal growth restriction (FGR) and severe sequelae in affected infants. Clinicians generally suspect cCMV based on multiple ultrasound (US) findings associated with cCMV. However, no studies have assessed the diagnostic accuracy of fetal US for cCMV-associated abnormalities in FGR. Eight FGR and 10 non-FGR fetuses prenatally diagnosed with cCMV were examined by undergoing periodic detailed US examinations, as well as postnatal physical and imaging examinations. The diagnostic accuracy of prenatal US for cCMV-associated abnormalities was compared between FGR and non-FGR fetuses with cCMV. The diagnostic sensitivity rates of fetal US for cCMV-related abnormalities in FGR vs. non-FGR fetuses were as follows: ventriculomegaly, 66.7% vs. 88.9%; intracranial calcification, 20.0% vs. 20.0%; cysts and pseudocysts in the brain, 0% vs. 0%; ascites, 100.0% vs. 100.0%; hepatomegaly, 40.0% vs. 100.0%; splenomegaly, 0% vs. 0%. The diagnostic sensitivity of fetal US for hepatomegaly and ventriculomegaly in FGR fetuses with cCMV was lower than that in non-FGR fetuses with cCMV. The prevalence of severe long-term sequelae (e.g., bilateral hearing impairment, epilepsy, cerebral palsy, and severe developmental delay) in the CMV-infected fetuses with FGR was higher, albeit non-significantly. Clinicians should keep in mind the possibility of overlooking the symptoms of cCMV in assessing fetuses with FGR.

Usefulness of Practitioner-Led Pancreatic Cancer Screening.

The 5-year survival rate for pancreatic cancer has improved (10%) but remains worse than that for other cancers. Early pancreatic cancer diagnosis is challenging, and delayed diagnosis can delay treatment, which impairs survival. Practitioners do not promptly refer cases to a general hospital, causing delayed discovery. Herein, we aimed to examine the usefulness of the Pancreatic Cancer Project in Matsue, whose objective is to detect pancreatic cancer in patients presenting at any medical institution in Matsue City. Clinical data were extracted from medical records, and abdominal ultrasonography and tumor marker blood level assessments were performed (n = 234; median age, 71 [range, 41-94] years; 51% male). Cases with abnormal abdominal ultrasonography or blood test findings were referred for specialist imaging and followed up. The pancreatic cancer detection rate was 6.0% (n = 14); all cases were referred to a general hospital by practitioners within 1 month. Patients had stage IA (n = 1), IIA (n = 6), IIB (n = 2), III (n = 1), and IV (n = 4) disease. Overall, pancreatic cancer could be detected at an earlier stage (I-II), but referral to a general hospital by visiting practitioners should be prompt. The Pancreatic Cancer Project in Matsue may help improve the detection and prognosis of pancreatic cancer.

The Current Challenges in Developing Biological and Clinical Predictors of Congenital Cytomegalovirus Infection.

Congenital cytomegalovirus (CMV) infection may cause severe long-term sequelae. Recent studies have demonstrated that early antiviral therapy for infants with symptomatic congenital CMV (cCMV) infection may improve neurological outcomes; thus, accurate identification of newborns at high risk of cCMV infection may contribute to improved outcomes in affected children. However, maternal serological screening for cCMV infection by diagnosing primary infection during pregnancy, which is a popular screening strategy, is inefficient, because the number of cCMV infections with nonprimary causes, including reactivation of or reinfection with CMV, is larger than that of cCMV infections with primary causes. Low levels of neutralizing antibodies against pentameric complex and potent CMV-specific T cell-mediated immune responses are associated with an increased risk of cCMV infection. Conversely, our prospective cohort studies revealed that the presence of maternal fever/flu-like symptoms, threatened miscarriage/premature delivery, or actual premature delivery are risk factors for cCMV infection among both women with normal pregnancies and those with high-risk ones, regardless of whether the infection is primary or nonprimary. This review focused on host immune responses to human CMV and current knowledge of potential biological and clinical factors that are predictive of cCMV infection.

Clinical factors associated with a placenta accreta spectrum.

INTRODUCTION: Placenta accreta spectrum (PAS) is a life-threating obstetric complication, and prenatal prediction of PAS can decrease maternal morbidity and mortality. The aim of this prospective cohort study was to determine the clinical factors associated with PAS. METHODS: Pregnant women who delivered at a university hospital were enrolled. Clinical data were collected from medical records, and logistic regression analyses were performed to determine which clinical factors were associated with PAS. RESULTS: Eighty-seven (2.1%) of the 4146 pregnant women experienced PAS. Multivariable analyses revealed that a prior history of cesarean section (CS) (OR 3.3; 95% CI 1.9-5.7; p < 0.01), dilation and curettage (D&C) (OR 2.8; 95% CI 1.7-4.6; p < 0.01), hysteroscopic surgery (OR 5.7; 95% CI 2.3-14.4; p < 0.01), uterine artery embolization (UAE) (OR 44.1; 95% CI 13.8-141.0; p < 0.01), current pregnancy via assisted reproductive technology (ART) (OR 4.1; 95% CI 2.4-7.1; p < 0.01), and the presence of placenta previa in the current pregnancy (OR 13.1; 95% CI 7.9-21.8; p < 0.01) were independently associated with the occurrence of PAS. CONCLUSION: Pregnant women who have a prior history of CS, D&C, hysteroscopic surgery, UAE, current pregnancy via ART, and the presence of placenta previa in the current pregnancy are high risk for PAS.

Immunoglobulin fetal therapy and neonatal therapy with antiviral drugs improve neurological outcome of infants with symptomatic congenital cytomegalovirus infection.

Infants with symptomatic congenital cytomegalovirus infection (cCMV) suffer from long-term sequelae. This study aimed at evaluating the efficacy of combining immunoglobulin (Ig) fetal therapy (FT) and neonatal therapy (NT) with antiviral drugs to improve neurological outcomes of affected infants. Women whose fetuses had symptomatic cCMV received Ig injection into the fetal peritoneal cavity and/or maternal blood as FT, while affected newborns received oral valganciclovir or intravenous ganciclovir as NT. We compared the neurological outcomes at ≥18 months old between infants receiving FT with or without NT (FT group) and those receiving NT only (NT group). From 2009-2019, 15 women whose fetuses had symptomatic cCMV received FT, while 19 newborns received NT only. In FT group, two newborns died, and two were <18 months old. Neurological outcomes of the remaining 11 infants in FT group were as follows: normal 45.5 %, mild impairments 36.4 %, and severe impairments 18.2 %. In NT group, one newborn died, one's parents refused the follow-up, one was <18 months old, and two had only chorioretinitis as symptoms. Neurological outcomes of the remaining 14 infants in NT group were as follows: normal 21.4 %, mild impairments 14.3 %, and severe impairments 64.3 %. The proportion of infants with severe impairments in FT group was significantly lower than that in NT group (18.2 % vs 64.3 %, p < 0.05). This is the first trial demonstrating that the combination of Ig FT and NT with antiviral drugs may be more effective in improving neurological outcomes of newborns with symptomatic cCMV as compared to NT only.

Biopsy remains indispensable for evaluating bone marrow involvement in DLBCL patients despite the use of positron emission tomography.

Initial staging by positron emission tomography/computed tomography (PET/CT) scanning is recommended for patients with diffuse large B-cell lymphoma (DLBCL). Whether both PET/CT and bone marrow biopsy (BMB) are required remains unclear. This study examined whether staging by PET/CT is sufficient. Participants with untreated DLBCL assessed using both PET/CT and BMB were included. Patients received independent diagnostic assessments from a radiologist and a hematopathologist. Both hematoxylin-eosin staining and CD20 immunostaining were performed to determine the bone marrow involvement in BMB. A total of 84 patients were included. The number of patients with positive bone marrow involvement identified by PET/CT and BMB was 16 (19%) and 22 (26%), respectively. Eight (10%) patients showed positive results in both tests. When considering BMB as a reference, PET/CT showed 36% sensitivity and 87% specificity, with positive and negative predictive values of 50% and 79%, respectively. BMB-positive patients had shorter progression-free (PFS) and overall (OS) survival than their BMB-negative counterparts. Compared to PET/CT-negative patients, patients with positive results did not show any significant differences in PFS and OS. However, among 16 PET/CT-positive patients, poor PFS and OS were observed among patients who were also BMB positive. BMB remains a mandatory step in staging of untreated DLBCL patients.

Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies.

This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1-6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6-11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8-27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1-6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

[Leukemic cell kinetics of APL with a novel complex variant t (12;17;15)(p13;q21;q22)].

A 69-year-old woman with leukocytopenia and thrombocytopenia was referred to our hospital. Her bone marrow comprised 70.5% abnormal promyelocytes that were positive for myeloperoxidase/CD33/CD117 and CD13 (dim) and negative for CD2/CD34/CD56 and HLA-DR. Chromosome analysis of the bone marrow showed t (12;17;15) (p13;q21;q22), and fluorescence in situ hybridization revealed the PML-RARA fusion signal only on the derivative chromosome 15. The patient was diagnosed with acute promyelocytic leukemia (APL) with PML-RARA and was treated using all-trans retinoic acid (ATRA). In peripheral blood (PB), PML-RARA-positive polymorphonuclear cells (PMNs) appeared on the second week and became negative on the sixth week after treatment, whereas PML-RARA-negative PMNs started to increase in number on the sixth week. Molecular remission was confirmed on the 10th week. Quantitative evaluation of the differentiated leukemic cells of APL and recovered cells from normal hematopoiesis in PB can provide useful information for a safer induction therapy. No significant difference was noted in the kinetics of the leukemic cells under ATRA treatment as well as in the clinical features between our patient without RARA-PML and those with t (15;17), which is a cytogenetic evidence for the critical role of PML-RARA in the pathogenesis of APL.

Clinical Factors Associated With Congenital Cytomegalovirus Infection: A Cohort Study of Pregnant Women and Newborns.

BACKGROUND: The aim of this prospective cohort study was to determine clinical factors associated with the occurrence of congenital cytomegalovirus infection (cCMV) in pregnant women. METHODS: Between March 2009 and November 2017, newborns born at a primary maternity hospital received polymerase chain reaction (PCR) analyses for CMV DNA in their urine with informed consent of the mothers at a low risk. Clinical data, including age, gravidity, parity, body mass index, occupation, maternal fever/flulike symptoms, pregnancy complications, gestational weeks at delivery, birth weight, and automated auditory brainstem response, were collected. Logistic regression analyses were performed to determine clinical factors associated with cCMV. RESULTS: cCMV was diagnosed by positive PCR results of neonatal urine in 9 of 4125 pregnancies. Univariate and multivariable analyses revealed that the presence of fever/flulike symptoms (odds ratio [OR], 17.9; 95% confidence interval [CI], 3.7-86.7; P < .001) and threatened miscarriage/premature labor in the second trimester (OR, 6.0; 95% CI, 1.6-22.8; P < .01) were independent clinical factors associated with cCMV. Maternal fever/flulike symptoms or threatened miscarriage/premature labor in the second trimester had 100% sensitivity, 53.2% specificity, and a maximum Youden index of .85. CONCLUSIONS: This cohort study for the first time demonstrated that these clinical factors of pregnant women and newborns were associated with the occurrence of cCMV. This is useful information for targeted screening to assess risks of cCMV in low-risk mothers, irrespective of primary or nonprimary CMV infection.