Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vaginal swabs of women with acute SARS-CoV-2 infection: a prospective study.

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is present in the vaginal secretions of both reproductive-aged and postmenopausal women during acute SARS-CoV-2 infection. DESIGN: Prospective study. SETTING: A single tertiary, university-affiliated medical centre in Israel. Time period, 1 June 2020 through to 31 July 2020. POPULATION: Women who were hospitalised in a single tertiary medical centre, who were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. METHODS: Women were diagnosed with acute SARS-CoV-2 infection by a nasopharyngeal RT-PCR test. Vaginal RT-PCR swabs were obtained from all study participants after a proper cleansing of the perineum. MAIN OUTCOME MEASURES: Detection of SARS-CoV-2 in vaginal RT-PCR swabs. RESULTS: Vaginal and nasopharyngeal swabs were obtained from 35 women, aged 21-93 years. Twenty-one women (60%) were in their reproductive years, of whom, five were in their third trimester of pregnancy. Most of the participants (57%) were healthy without any underlying medical conditions. Of the 35 patients sampled, 2 (5.7%) had a positive vaginal RT-PCR for SARS-CoV-2, one was premenopausal and the other was a postmenopausal woman. Both women had mild disease. CONCLUSION: Our findings contradict most previous reports, which did not detect the presence of viral colonisation in the vagina. Although passage through the birth canal exposes neonates to the vaginal polymicrobial flora, an acquisition of pathogens does not necessarily mandate neonatal infection or clinical disease. Nevertheless, when delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation, even if it is uncommon. TWEETABLE ABSTRACT: When delivering the infant of a woman with acute SARS-CoV-2 infection, a clinician should consider the possibility of vaginal colonisation.

Conservative management of preterm premature rupture of membranes beyond 32 weeks' gestation: is it worthwhile?

We aimed to investigate whether conservative management of preterm premature rupture of membranes (PPROM) at 32-34 weeks' gestation improves outcome. In this retrospective analysis of singleton pregnancies, the study group included patients with PPROM at 28-34 weeks' gestation and the control group included patients presented with spontaneous preterm delivery at 28-34 weeks' gestation. Both groups were subdivided according to gestational age - early (28-31 weeks' gestation) versus late (32-34 weeks' gestation). Adverse neonatal outcome included neonatal death, intraventricular haemorrhage grade 3/4, respiratory distress syndrome, periventricular leucomalacia and neonatal sepsis. The study and control groups included 94 and 86 women, respectively. The study group had a lower incidence of adverse neonatal outcome at the earlier weeks (28-31), compared with the control group at the same gestational age. In contrast, at 32-34 weeks' gestation no difference in the risk for adverse neonatal outcome was noticed. Additionally, within the study group, chorioamnionitis rate was significantly higher among those who delivered at 32-34 weeks' gestation (p < 0.01). No advantage for conservative management of PPROM was demonstrated beyond 31 weeks' gestation. Moreover, conservative management of PPROM at 32-34 weeks' gestation may expose both mother and neonate to infectious morbidity.

12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival.

Considerable evidence has been published demonstrating the importance of lipoxygenase enzymes for vascular smooth muscle cell (VSMC) growth. The current study sets out to determine whether or not 12-lipoxygenase (12LO) is also important for human placental VSMC survival. Both a pharmacological and two 12LO antisense knockdown approaches were applied. The 12LO inhibitor baicalien induced a 2-2.5-fold increase in cell death, which appeared to result from apoptosis, as indicated by DNA fragmentation, activation of procaspase 3 to caspase 3 and cytochrome C release from the mitochondria to the cytosol. This apoptosis could be prevented by treatment with the 12LO product, 12 hydroxyeicosatetraenoic acid (12HETE). Human platelet-type 12LO-antisense knockdown, by either plasmid transfection or adeno-associated virus (AAV) infection also induced substantial VSMC death over controls, which could also be prevented by treatment with 12HETE, but not 5HETE. Hence, biochemical 12LO inhibition or 12LO-antisense knockdown in VSMC can induce programmed cell death. These observations suggest a previously unrecognized association between human VSMC survivability and 12LO.

Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4.

Stem cell homing and repopulation are not well understood. The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 were found to be critical for murine bone marrow engraftment by human severe combined immunodeficient (SCID) repopulating stem cells. Treatment of human cells with antibodies to CXCR4 prevented engraftment. In vitro CXCR4-dependent migration to SDF-1 of CD34+CD38-/low cells correlated with in vivo engraftment and stem cell function. Stem cell factor and interleukin-6 induced CXCR4 expression on CD34+ cells, which potentiated migration to SDF-1 and engraftment in primary and secondary transplanted mice. Thus, up-regulation of CXCR4 expression may be useful for improving engraftment of repopulating stem cells in clinical transplantation.

Listeriosis in pregnancy: under-diagnosis despite over-treatment.

OBJECTIVE: To compare the symptomatology of pregnant women with suspected listeriosis to culture confirmed listeriosis. STUDY DESIGN: All cases of suspected and culture confirmed pregnancy-associated listeriosis from a single center were retrospectively reviewed assessing demographics, clinical, laboratory and pathological findings, and maternal, fetal and neonatal outcomes. RESULTS: Listeriosis was identified in seven patients, none of whom belonged to the 117 women with suspected listeriosis. Women with confirmed infection were more likely to exhibit fever (P=0.01), flu-like symptoms (P=0.006), threatened preterm labor (P=0.05) and inflammatory markers (P=0.02), but less likely to exhibit gastrointestinal complaints (P=0.004) in comparison with suspected non-confirmed cases. Confirmed cases resulted in preterm delivery (n=5) and stillbirth (n=2). Neonatal complications included meningitis, respiratory disease and sepsis. Maternal outcomes were favorable. CONCLUSION: Although 'febrile gastroenteritis' is a poor predictor of listeriosis in pregnancy, fever, premature contractions and inflammatory markers are important risk indices prompting workup and adequate empiric treatment.

Cardiac hemodynamics before, during and after elective cesarean section under spinal anesthesia in low-risk women.

OBJECTIVE: The aim of this study was to describe maternal central hemodynamic parameters before and during delivery as well at the early puerperium in healthy women undergoing elective cesarean section (CS) at term. STUDY DESIGN: The noninvasive Cardiac System (NICaS, NI Medical, Petah-Tikva, Israel) is a regional impedance device that measures cardiac output (CO) and its derivatives with a good correlation with the gold standard Swan-Ganz catheter. We performed a prospective longitudinal study of healthy women with a singleton pregnancy at term. Maternal hemodynamic parameters were assessed by the NICaS at six time points: a few minutes before undergoing an elective CS, immediately after receiving spinal anesthesia, immediately after delivery of the fetus and placenta, after abdominal fascia closure, and within 24 to 36 and 48 to 72 h postpartum. RESULT: Sixty-one consenting women were recruited during the study period (January 2015 to June 2015). Baseline (pre-CS) mean arterial pressure (MAP) was 87.7±7.9 mm Hg, baseline CO was 7.5±1.7 l per min and baseline total peripheral resistance (TPR) was 994±301 dyne × s per cm5. After spinal anesthesia CO significantly increased by 13%, no significant changes were observed in MAP or TPR. Immediately after delivery, a nadir for all parameters was reached: MAP and TPR were significantly reduced by 8% and 26%, respectively (comparing to pre-CS), and CO further increased by 9% (24% comparing to pre-CS). After fascia closure, partial recoveries of all parameters were observed. Twenty-four to thirty-six hours postpartum MAP returned to pre-CS values, while CO and TPR reached -9% and +11% comparing to baseline, respectively. None of the parameters differed significantly between 24 to 36 and 48 to 72 h postpartum. CONCLUSION: Significant hemodynamic changes (reduction of TPR and increase of CO) take place at the time of delivery of fetus and placenta. Knowledge of normal hemodynamic values using a reliable noninvasive technique during various stages of pregnancy and the postpartum period is feasible, and might assist clinicians in assessing the level of patient deviation from expected cardiac performance, especially in high-risk women.

The effect of glucose administration on perceived fetal movements in women with decreased fetal movement, a double-blinded placebo-controlled trial.

OBJECTIVE: To assess the effect of maternal glucose administration on perceived fetal movements. STUDY DESIGN: This was a randomized, double-blinded placebo-controlled trial. Patients 28-41 weeks singleton gestation complaining of decreased fetal movements (DFM) were assigned to receive either 500 cc dextrose 5% (group A) or 500 cc normal saline (group B) intravenously. Primary outcome was number of fetal movements recorded during the following 30 min. Secondary outcomes included need for admission or induction of labor owing to persistent DFM. Maternal glucose levels were taken before and after intervention. A sample size of 50 patients was planned in order to detect a 30% increase in fetal movements in group A. RESULTS: Between February 2011 and April 2013, 50 patients were recruited. Demographic characteristics were similar among groups. There was no difference in the number of fetal movements recorded (7±6 vs 8.8±6 movements/30 min, group A and B, respectively, P=0.39). Similar number of patients had persistent DFM that required admission (8 vs 10 patients, P=0.77, OR 1.4, confidence interval (CI) 0.38-5.3); of those admitted, similar number of patients had induction of labor (3 vs 6 patients, P=0.64, OR 0.4, CI 0.03-3.8). Maternal glucose levels were similar at recruitment (88±19 vs 83±15 mg dl(-1) P=0.36) but were significantly higher in group A (161±37 vs 75±15 mg dl(-1) P<0.0001) after intervention. CONCLUSION: In women with DFM, maternal glucose administration has no effect on perceived fetal movement and its clinical use is questionable.

Isolated proteinuria is a risk factor for pre-eclampsia: a retrospective analysis of the maternal and neonatal outcomes in women presenting with isolated gestational proteinuria.

OBJECTIVE: To examine maternal and neonatal outcomes of isolated proteinuria and define maternal characteristics for progression to pre-eclampsia. STUDY DESIGN: Retrospective cohort study. Data from all hospitalized pregnant women between 2009 and 2014 with new onset isolated proteinuria of over 300 mg/24 h at admission were obtained. Follow-up was performed from the time of admission to the hospital to the time of discharge postpartum. Obstetrical, maternal and neonatal outcomes were obtained. RESULT: Ninety-five pregnant women diagnosed with new onset isolated proteinuria were followed to term. Thirteen women developed pre-eclampsia during pregnancy and eight developed pre-eclampsia postpartum. Maternal characteristics for progression to pre-eclampsia were greater maximal values of proteinuria. Earlier pre-eclampsia onset was associated with early-onset proteinuria and multiple gestation. Although greater values of proteinuria were associated with increased risk for intrauterine growth restriction and lower Apgar scores, maternal outcome was favorable, regardless of pre-eclampsia progression. Isolated proteinuria progressing to pre-eclampsia was associated with late pre-eclampsia onset and favorable maternal and neonatal outcomes. CONCLUSION: A significant proportion of women with new onset isolated proteinuria will develop pre-eclampsia. In these women, close follow-up is recommended until after delivery.

Calciotrophic hormones and hyperglycemia modulate vitamin D receptor and 25 hydroxyy vitamin D 1-α hydroxylase mRNA expression in human vascular smooth muscle cells.

Estrogen receptors (ERα and ERß), the vitamin D receptor (VDR) and 25 hydroxyy vitamin D 1-α hydroxylase (1OHase) mRNA are expressed in vascular smooth muscle cells (VSMC). In these cells estrogenic hormones modulate cell proliferation as measured by DNA synthesis (DNA). In the present study we determined whether or not the calciotrophic hormones PTH 1-34 (PTH) and less- calcemic vitamin D analog QW as well as hyperglycemia can regulate DNA synthesis and CK. E2 had a bimodal effect on VSMC DNA synthesis, such that proliferation was inhibited at 30nM but stimulated at 0.3nM. PTH at 50nM increased, whereas QW at 10nM inhibited DNA synthesis. Hyperglycemia inhibited the effects on high E2, QW and PTH on DNA only. Both QW and PTH increased ERα mRNA expression, but only PTH increased ERß expression. Likewise, both PTH and QW stimulated VDR and 1OHase expression and activity. ERß, VDR and 1OHase expression and activity were inhibited by hyperglycemia, but ERα expression was unaffected by hyperglycemia. In conclusion, calcitrophic hormones modify VSMC growth and concomitantly affect ER expression in these cells as well as the endogenous VSMC vitamin D system elements, including VDR and 1OHase. Some of the later changes may likely participate in growth effects. Of importance in the observation is that several regulatory effects are deranged in the presence of hyperglycemia, particularly the PTH- and vitamin D-dependent up regulation of VDR and 1OHase in these cells. The implications of these effects require further studies. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

Hepatic infarctions during pregnancy are associated with the antiphospholipid syndrome and in addition with complete or incomplete HELLP syndrome.

Antiphospholipid antibody syndrome (APS) is associated with adverse pregnancy outcomes and maternal complications including thrombotic events and early pre-eclampsia. HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) represents a unique form in the spectrum of pre-eclampsia. This report describes four patients with pregnancy-associated hepatic infarctions. All four had APS and HELLP syndrome, which was complete in one patient and incomplete in three patients, with elevated liver enzymes in all, and either thrombocytopenia or hemolysis in two. In the literature, we found descriptions of an additional 24 patients who had 26 pregnancies with concomitant hepatic infarction. Of the total 28 patients, anticardiolipin antibodies (aCL) and/or lupus anticoagulant (LAC) were assessed in 16 patients, out of whom 15 were found to be positive. Hepatic infartction during pregnancy was associated almost always with APS, with HELLP (2/3 complete, 1/3 incomplete), and only in one-third of the pregnancies with pre-eclampsia (PE).

Detection and quantitative evaluation of lupus circulating anticoagulant activity.

Sixty-six SLE patients were studied for the presence of lupus type circulating anticoagulant. Forty-nine percent of them showed activity of this anticoagulant. The sensitivity of various coagulation tests was compared. Recalcification time was found to be the most sensitive screening test and the kaolin clotting time mixture test, the best for determining the presence of the anticoagulant. Tissue thromboplastin inhibition test detected only half of the patients in whom the anticoagulant was found by recalcification time and kaolin clotting time mixture test. APTT, using 2 different reagents, resulted in 73% and 52% false negatives. A numerical index for determining the presence of the anticoagulant and its quantitative evaluation is suggested. The association between thromboembolic events, recurrent abortions and the different coagulation tests is shown.

Low molecular weight heparin and warfarin in the treatment of patients with antiphospholipid syndrome during pregnancy.

Fifty-seven pregnancies in women with antiphospholipid syndrome (APS) are presented. These were treated with s.c. enoxaparin and low dose aspirin. In fourteen pregnancies warfarin was prescribed between weeks 15-34 (warfarin group). The decision to switch to warfarin depended on a morbidity score, and the patient's consent. Neither teratogenicity nor significant maternal, fetal or neonatal hemorrhage was observed. Despite the higher pretreatment morbidity score of the warfarin group, the live birth rate was high in both groups: 86% in the warfarin group and 87% in the non-warfarin group. There was no significant difference in week of delivery, birth weight, or incidence of thrombosis between the groups. The study demonstrates the efficacy and safety of anticoagulants during pregnancy. The use of LMWH in pregnant women with APS not being moot, warfarin might be justified in selected patients.

Increased xanthine oxidase during labour--implications for oxidative stress.

Xanthine dehydrogenase/oxidase (XDH/XO) produces uric acid. When in the oxidase form, this production is coupled with the generation of free radicals. Hypoxia-reperfusion enhances conversion of XDH to XO. Since the placenta is exposed to short periods of hypoxia reperfusion during labour, 17 placentae of pregnancy terminated by elective caesarean section and five placentae of pregnancies terminated by caesarean section during labour were examined for XDH/XO activity. It was found that XO activity was higher in the placentae of labouring women (P = 0.003), which suggests that labour enhances conversion of XDH to XO, facilitating free radical production.

Xanthine oxidase/dehydrogenase is present in human placenta.

Xanthine dehydrogenase/oxidase (XDH, EC 1.1.1.204, XO, EC 1.2.3.2) produces uric acid, and in the oxidase form also generates the free radical superoxide. Previous reports failed to demonstrate XDH/XO activity in human placenta. Our objective was to determine evidence of XDH/XO in human placenta. We developed a cDNA probe for human XDH/XO and used it to detect mRNA by Northern hybridization. Immunohistochemical localization of the enzyme in placental tissue was performed using a specific antibody for XDH/XO and ABC-peroxidase. Enzyme activity assay was determined by the conversion of [14C] xanthine to [14C] uric acid. mRNA was detected in all placental samples (n = 4). Villous and non-villous trophoblast cells expressed immunohistochemical staining for XOD (n = 4). Enzyme activity was detected in all placentae (n = 6). Despite previous reports, we found mRNA, XDH/XO protein and enzyme activity in human placenta localized to trophoblast cells. Enzyme activity was much lower than in liver. Several conditions in the maternal-fetal unit could potentially increase XDH/XO activity and conversion of the enzyme to its oxidase form.

Placental apoptosis in discordant twins.

OBJECTIVE: To investigate placental apoptosis in discordant dichorial twins. METHODS: Placental samples were obtained from 7 third-trimester suitable twins. Discordancy was defined as a >25 per cent difference in newborn birth weight. Light microscopy using hematoxylin and eosin (H&E)-stained paraffin slides and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling (TUNEL) methods were used to confirm the incidence of apoptosis. Investigators were blinded to pregnancy outcome. RESULTS: Both methods revealed that the incidence of apoptosis in the placentas of the smaller fetuses was significantly higher than in placentas of the larger fetuses. The incidence of TUNEL-positive cells in the former was 1.4+/-0.26 per cent: this was significantly higher than the incidence of apoptosis in the placental specimens of the latter (0.9+/-0.07 per cent, P< 0.02 Wilcoxon rank test). The same results were obtained with H&E: the incidence of apoptosis detected in placentas from the former was 1.07+/-0.1 per cent compared to 0.72+/-0.08 per cent in those of the latter (P< 0.02 Wilcoxon rank test). CONCLUSIONS: Despite similar environment conditions, placental apoptosis is increased in the smaller fetus and thus might play a role in discordancy between twins. Since increased placental apoptosis has also been found in singleton intrauterine growth restriction, this supports the hypothesis that the smaller twin is selectively growth restricted.

Acute lymphoblastic leukemia subtypes in Israel: the Sheba medical center experience.

During the period from 1978 to 1981, 52 patients with ALL were diagnosed and treated at the Chaim Sheba Medical Center. Using standard cell markers to subtype the blasts, 49 of the patients could be classified: 16 were found to be T-cell ALL, 10 common ALL, five null ALL, four pre-B and 14 were partially characterized as non-B, non-T. Analysis of the series revealed two distinctive features: high prevalence (30%) of T-cell ALL among both Jews and Arabs and a high proportion, two-thirds, of high risk patients due to high initial WBC counts, unfavourable age or T-cell characteristics. The minimal incidence of ALL among the Gaza Strip Arab children during the study period is 4:100,000, which is close to the incidence in the Western world. During previous years the leukemia incidence in the Gaza Strip was very low while the most common lymphatic malignancies were Burkitt tumor and other non-Hodgkin lymphomas.

Aspergillosis in systemic lupus erythematosus.

Infection is the major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although various fungi account for a substantial number of these lethal infections, aspergillosis, an important opportunistic infection in immunosuppressed patients, is described rarely. Only 23 cases have been reported in the English-language medical literature. Risk factors for acquiring aspergillosis in these patients were high grade disease activity, granulocytopenia, use of steroids and other immunosuppressive treatment and presence of bacterial infection. The diagnosis in most patients was delayed and they died. Here, we describe three SLE patients with invasive aspergillosis. Features of our patients' diseases were similar to those reported previously. Aspergillosis appeared while they had active SLE treated with high dose corticosteroids. In 2 patients the fungal infection was systemic and diagnosed post mortem. Both were leukopenic and had concurrent bacterial infection and one received amphotericin B prior to death. In the third, the infection was localized to a transplanted kidney and was cured by nephrectomy. Aspergillosis should be suspected in patients with active SLE, who are immunocompromised and sustain concomitant bacterial infections. The currently poor prognosis may be improved with more aggressive diagnostic investigation and treatment.

Outcome of pregnancy in three patients with primary antiphospholipid syndrome after stroke.

OBJECTIVE: Ischemic stroke is the most common neurological manifestation in patients with antiphospholipid syndrome (APS). Pregnancy in APS patients markedly increases the risk of thrombosis. There is no data on pregnancy outcome in patients with APS with a history of an ischemic stroke. We report our experience with three APS patients with a history of stroke who had successful pregnancies and deliveries. PATIENTS: Three patients with APS and previous stroke were treated with small doses of aspirin and anticoagulants during pregnancy. RESULTS: The patients remained free of attacks of cerebral ischemia during their pregnancies and at follow-up periods of 1 to 4 years. CONCLUSIONS: Successful pregnancy and delivery is possible in APS patients with a history of stroke, treated with low-dose aspirin and anticoagulants. A previous episode of cerebral ischemia should not be considered an absolute contraindication for an APS patient to become pregnant.

The association between polyhydramnios and preterm delivery.

OBJECTIVE: To determine whether an association exists between the severity of polyhydramnios and the frequency of preterm delivery. METHODS: The study group consisted of 275 singleton pregnancies with polyhydramnios as defined by an amniotic fluid index (AFI) of at least 25 cm. Polyhydramnios was arbitrarily categorized into three groups by severity: mild (AFI 25-30 cm), moderate (AFI 30.1-35 cm), and severe (AFI greater than 35.1 cm). A delivery was considered preterm if it occurred before 37 weeks' gestation. RESULTS: Fifty-two of 275 (18.9%) women delivered before 37 weeks' gestation. Preterm delivery occurred in 37 of 199 (18.5%) cases with mild polyhydramnios, 12 of 55 (21.8%) with moderate polyhydramnios, and three of 21 (14.3%) with severe polyhydramnios (no statistically significant difference). Fetuses with congenital malformations (16 of 41, 39%) and those of diabetic mothers (ten of 45, 22.2%) had a significantly higher incidence of preterm delivery than did cases with unexplained polyhydramnios (24 of 190, 12.6%; P < .001). The prematurity rate in cases with idiopathic polyhydramnios was no higher than the overall rate for our hospital. CONCLUSION: The underlying cause of polyhydramnios, rather than the relative excess of amniotic fluid as defined by this study, appears to determine when preterm labor will occur.

Severe preeclampsia and high frequency of genetic thrombophilic mutations.

OBJECTIVE: To determine whether severe preeclampsia is associated with genetic thrombophilic mutations or other types of thrombophilia. METHODS: A case-control study compared 63 consecutive women with severe preeclampsia evaluated at our institution between November 1997 and April 1999 with 126 control women matched for age and ethnicity. All of these women were tested several months after delivery for mutations of factor V Leiden, methylenetetrahydrofolate reductase, and prothrombin gene; for deficiencies of protein C, protein S, and antithrombin-III; and for the presence of anticardiolipin antibodies. RESULTS: Thirty-five study women (56%) had a thrombophilic mutation compared with 24 control women (19%), P <.001. Seven other study women (11%) had other thrombophilias, compared with one control woman (0.8%), P <.01. Within the study group, women with thrombophilia delivered at an earlier gestational age, and their neonates' birth weights were lower compared with those of women without thrombophilia. CONCLUSION: Because thrombophilia was found in 67% of women with severe preeclampsia, we suggest that women who have severe preeclampsia should be tested for thrombophilia.