Acute pyelonephritis during pregnancy: a systematic review of the aetiology, timing, and reported adverse perinatal risks during pregnancy.

We performed a comprehensive systematic review of acute pyelonephritis in pregnancy using PubMed, SCOPUS, ClinicalTrials.gov, and Ovid from inception to April 2018. About 7796 references were screened for inclusion, and 52 references from 1908 to 2017 were included. One hundred seven cases of acute pyelonephritis in pregnant women were reviewed. Gestational age at diagnosis was reported as 2 (2%), 43 (40%), and 51 (52%) during the first, second, and third trimesters, respectively. Maternal complications included sepsis (49%), acute respiratory distress syndrome (47%), anaemia (33%), acute kidney injury (10%), renal abscess (6%), and death (6%). 25 preterm deliveries (23%), 6 intrauterine foetal demises (6%), 4 spontaneous abortions (4%), and 8 neonatal intensive care unit admissions (7%) were reported. Microorganisms cultured included Escherichia coli (51%), Klebsiella (8%), Proteus (5%), Staphylococcus aureus (5%), Streptococcus (4%), and Enterococcus (3%). Early diagnosis and management led to fewer complications.Impact statementWhat is already known on this subject? Acute pyelonephritis during pregnancy can lead to adverse pregnancy outcomes and in this article, we highlight the most common outcomes previously reported. Previous studies have reported maternal adverse outcomes and only very few stressed on fetal/neonatal outcomes.What do the results of this study add? The results add that not only is maternal morbidity/mortality is increased, but also increases adverse outcomes for the fetus/neonate, such as preterm delivery and fetal/neonatal demise.What are the implications of these findings for clinical practice and/or further research? The implications from this article serve to increase a medical providers knowledge on how to appropriately counsel pregnant women with acute pyelonephritis. In addition, future research can aim to understand why pregnant women are more prone to morbidity and mortality compared to nonpregnant women.

In vitro model for the assessment of human immune responses to subunit RSV vaccines.

Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract disease in infants and young children worldwide and a high priority for vaccine development. Despite over 50 years of research, however, no vaccine is yet available. One block to vaccine development is an incomplete understanding of the aberrant memory response to the formalin-inactivated RSV vaccine (FI-RSV) given to children in the 1960s. This vaccine caused enhanced respiratory disease (ERD) with later natural RSV infection. Concern that any non-live virus vaccine may also cause ERD has blocked development of subunit vaccines for young children. A number of animal FI-RSV studies suggest various immune mechanisms behind ERD. However, other than limited data from the original FI-RSV trial, there is no information on the human ERD-associated responses. An in vitro model with human blood specimens may shed light on the immune memory responses likely responsible for ERD. Memory T cell responses to an antigen are guided by the innate responses, particularly dendritic cells that present an antigen in conjunction with co-stimulatory molecules and cytokine signaling. Our in vitro model involves human monocyte derived dendritic cells (moDC) and allogenic T cell cultures to assess innate responses that direct T cell responses. Using this model, we evaluated human responses to live RSV, FI-RSV, and subunit RSV G vaccines (G-containing virus-like particles, G-VLP). Similar to findings in animal studies, FI-RSV induced prominent Th2/Th17-biased responses with deficient type-1 responses compared to live virus. Responses to G-VLPs were similar to live virus, i.e. biased towards a Th1 and not a Th2/Th17. Also mutating CX3C motif in G gave a more pronounced moDC responses associated with type-1 T cell responses. This in vitro model identifies human immune responses likely associated with ERD and provides another pre-clinical tool to assess the safety of RSV vaccines.

Cerebral pontine infarctions during pregnancy - A case report and review of the literature.

Cerebrovascular disease is not uncommon during pregnancy as a result of either venous or arterial occlusion, or a hemorrhagic event, resulting in ischemia. Pregnancy may alter the prognosis of these neurologic disorders, with increased risks of morbidity and mortality for the mother and the developing fetus. Etiologies of stroke during pregnancy and the postpartum period include preeclampsia, eclampsia, HELLP syndrome, posterior reversible encephalopathy syndrome (PRES), amniotic fluid embolism, postpartum angiopathy, postpartum cardiomyopathy, thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), cerebral venous thrombosis, CNS infections, and maternal thrombophilia. Essentially any of the vessels in the brain can be involved in cerebral infarction; however, pontine infarctions are rare and are generally secondary to occlusive insults or after dissection of an aneurysm. Though not common, these conditions can result in devastating sequelae and significant disability. Scant literature is available regarding pontine infarctions during pregnancy. Here we present a rare case of a pregnant patient who presented with new-onset seizures and was found to have a cerebral pontine infarction on imaging. The purpose of this article is to summarize existing data regarding the incidence, risk factors, and potential etiologies, as well as treatment strategies for pontine infarctions during pregnancy.

Unilateral Open-lip Schizencephaly with Tonsillar Herniation in a Preterm Infant.

Schizencephaly is a rare type of neuronal migration disorder characterized by the presence of a cerebral hemispheric cleft that extends from lateral ventricles to the cortical surface of the brain. We report a rare case of prenatally diagnosed unilateral schizencephaly in a late preterm infant who manifested with rapidly progressive hydrocephalus with massive enlargement of posterior cerebrospinal fluid spaces with tonsillar herniation that was successfully treated with placement of a ventriculoperitoneal shunt.

Botulism in pregnancy - a clinical approach to diagnosis and management.

Botulism is a life-threatening toxin mediated disease that often presents with a sudden rapid onset of paralysis of their skeletal muscles with subsequent respiratory compromise and sudden death. Given the natural physiological changes during pregnancy, pregnant women with botulism may experience a more exaggerated course and have worse outcomes compared to nonpregnant women. Medical providers caring for such patients should not only maintain a high level of suspicion for botulism, but administration of an antitoxin early in their care can help reduce morbidity and mortality, while awaiting confirmatory laboratory results. It is not uncommon for a medical provider caring for these women to mistakenly associate the signs and symptoms associated with botulism with pregnancy-related findings; therefore, this article illustrates a clinical algorithmic approach to caring for these women, including a systematic approach to establishing a diagnosis and management plan for pregnant women with botulism.

Human endometrial stromal cell plasticity: Reversible sFlt1 expression negatively coincides with decidualization.

Preeclampsia (PE) is a major complication of pregnancy in which the placenta is known to have shallow implantation into the uterine decidua. Studies have implicated soluble fms-like tyrosine kinase-1 (sFlt1), a soluble vascular endothelial growth factor (VEGF) receptor protein, in the pathogenesis of PE. sFlt1 has the ability to bind to and neutralize the angiogenic functions of VEGF and placental growth factor (PlGF). The presence of sFlt1 and its action in the endometrium is yet to be determined. We hypothesize that endometrial stromal cells (ESC) at the maternal-fetal interface may play a role in sFlt-1 regulation during pregnancy. In this study, we seek to understand the dynamic regulation of sFlt1 production in primary human ESC as a result of hormone stimulation and withdrawal. To mimic a biphasic menstrual cycle, ESC were treated with cAMP to induce endometrial decidualization that occurs during the luteal secretory phase, followed by cAMP withdrawal reflecting the follicular proliferative phase. Here, we present data to show that (1) ESC produce detectable amounts of sFlt1, (2) sFlt1 expression is turned off during decidualization at both the protein and RNA level (3) ESC decidualization and resulting sFlt1 expression are reversible phenomenon, and (4) Decidualization markers prolactin (PRL) and VEGF expressions in ESC are negatively correlated with sFlt1. These findings may have important implications in diseases such as PE that involve abnormal decidualization, implantation and angiogenesis at the maternal-fetal interface.

Pharmacokinetics and Placental Transfer of Elvitegravir, Dolutegravir, and Other Antiretrovirals during Pregnancy.

The integrase inhibitors elvitegravir (EVG) and dolutegravir (DTG) rapidly decrease the plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentrations of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMCs), or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood and within placentae from HIV-1-infected pregnant women. Maternal blood and cord blood were obtained from women receiving EVG, cobicistat, tenofovir disoproxil fumarate, and emtricitabine as a single fixed-dose combination formulation or DTG as part of a combination regimen. Plasma and PBMCs from maternal and cord blood were obtained along with villous placental samples. Drug concentrations were simultaneously determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Utilizing medians and ranges to interpret our data, we compared the drug concentration ratios between different matrices (maternal and cord blood plasma, PBMCs, and placenta). All five agents transferred from maternal into fetal circulation via the placenta. Concentration ratios for EVG, cobicistat, tenofovir, and emtricitabine (n = 10) and DTG (n = 3) were determined between cord plasma and placenta, cord and maternal plasma, and cord PBMCs and maternal PBMCs. TFV moves from maternal plasma through the placenta to the cord blood and then into cord PBMCs, where it is phosphorylated into its active forms (TFV diphosphate). These five ARVs were detected in each of the compartments, highlighting transfer of these agents from the maternal into the fetal circulation.

Botulism During Pregnancy and the Postpartum Period: A Systematic Review.

Background: Maternal and fetal outcomes associated with botulism and botulinum antitoxin use during pregnancy and the postpartum period have not been systematically reviewed. Methods: We searched Global Health, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Scopus, and Medline databases from inception to May 2015 for studies published on botulism or botulinum antitoxin use during pregnancy and the postpartum period, as well as the Centers for Disease Control and Prevention National Botulism Surveillance database. Our search identified 4517 citations. Results: Sixteen cases of botulism during pregnancy (11 in the third trimester) and 1 case during the postpartum period were identified. Ten cases were associated with confirmed or likely foodborne exposure; 2 cases were attributed to wound contamination related to heroin use, and the source of 5 cases was unknown. Eleven women with botulism had progressive neurologic deterioration and respiratory failure, requiring intensive care unit admission. Four women had adverse outcomes, including 2 deaths and 2 women who remained in a persistent vegetative state. No neonatal losses or cases of congenital botulism were reported. Among the 12 cases that reported neonatal data, 6 neonates were born preterm. No adverse maternal or neonatal events were identified as associated with botulinum antitoxin therapy among 11 patients who received it. Conclusions: Our review of 17 cases of botulism in pregnant/postpartum women found that more than half required ventilator support, 2 women died, and 6 infants were born prematurely. A high level of clinical suspicion is key for early diagnosis and treatment of botulism. Care of pregnant women or new mothers with botulism can include preparation for possible intubation.

Management of HIV Infection during Pregnancy in the United States: Updated Evidence-Based Recommendations and Future Potential Practices.

All HIV-infected women contemplating pregnancy should initiate combination antiretroviral therapy (cART), with a goal to achieve a maternal serum HIV RNA viral load beneath the laboratory level of detection prior to conceiving, as well as throughout their pregnancy. Successfully identifying HIV infection during pregnancy through screening tests is essential in order to prevent in utero and intrapartum transmission of HIV. Perinatal HIV transmission can be less than 1% when effective cART, associated with virologic suppression of HIV, is given during the ante-, intra-, and postpartum periods. Perinatal HIV guidelines, developed by organizations such as the World Health Organization, American College of Obstetricians and Gynecologists, and the US Department of Health and Human Services, are constantly evolving, and hence the aim of our review is to provide a useful concise review for medical providers caring for HIV-infected pregnant women, summarizing the latest and current recommendations in the United States.

Zika Virus Infects Human Placental Macrophages.

The recent Zika virus (ZIKV) outbreak in Brazil has been directly linked to increased cases of microcephaly in newborns. Current evidence indicates that ZIKV is transmitted vertically from mother to fetus. However, the mechanism of intrauterine transmission and the cell types involved remain unknown. We demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in primary human placental macrophages, called Hofbauer cells, and to a lesser extent in cytotrophoblasts, isolated from villous tissue of full-term placentae. Viral replication coincides with induction of type I interferon (IFN), pro-inflammatory cytokines, and antiviral gene expression, but with minimal cell death. Our results suggest a mechanism for intrauterine transmission in which ZIKV gains access to the fetal compartment by directly infecting placental cells and disrupting the placental barrier.

Integrase inhibitors in late pregnancy and rapid HIV viral load reduction.

BACKGROUND: Minimizing time to HIV viral suppression is critical in pregnancy. Integrase strand transfer inhibitors (INSTIs), like raltegravir, are known to rapidly suppress plasma HIV RNA in nonpregnant adults. There are limited data in pregnant women. OBJECTIVE: We describe time to clinically relevant reduction in HIV RNA in pregnant women using INSTI-containing and non-INSTI-containing antiretroviral therapy (ART) options. STUDY DESIGN: We conducted a retrospective cohort study of pregnant HIV-infected women in the United States from 2009 through 2015. We included women who initiated ART, intensified their regimen, or switched to a new regimen due to detectable viremia (HIV RNA >40 copies/mL) at ≥20 weeks gestation. Among women with a baseline HIV RNA permitting 1-log reduction, we estimated time to 1-log RNA reduction using the Kaplan-Meier estimator comparing women starting/adding an INSTI in their regimen vs other ART. To compare groups with similar follow-up time, we also conducted a subgroup analysis limited to women with ≤14 days between baseline and follow-up RNA data. RESULTS: This study describes 101 HIV-infected pregnant women from 11 US clinics. In all, 75% (76/101) of women were not taking ART at baseline; 24 were taking non-INSTI containing ART, and 1 received zidovudine monotherapy. In all, 39% (39/101) of women started an INSTI-containing regimen or added an INSTI to their ART regimen. Among 90 women with a baseline HIV RNA permitting 1-log reduction, the median time to 1-log RNA reduction was 8 days (interquartile range [IQR], 7-14) in the INSTI group vs 35 days (IQR, 20-53) in the non-INSTI ART group (P < .01). In a subgroup of 39 women with first and last RNA measurements ≤14 days apart, median time to 1-log reduction was 7 days (IQR, 6-10) in the INSTI group vs 11 days (IQR, 10-14) in the non-INSTI group (P < .01). CONCLUSION: ART that includes INSTIs appears to induce more rapid viral suppression than other ART regimens in pregnancy. Inclusion of an INSTI may play a role in optimal reduction of HIV RNA for HIV-infected pregnant women presenting late to care or failing initial therapy. Larger studies are urgently needed to assess the safety and effectiveness of this approach.

Fetal Implications of Diagnostic Radiation Exposure During Pregnancy: Evidence-based Recommendations.

The purpose of this article is to review the fetal and long-term implications of diagnostic radiation exposure during pregnancy. Evidence-based recommendations for radiologic imaging modalities utilizing exposure of diagnostic radiation during pregnancy, including conventional screen-film mammography, digital mammography, tomosynthesis, and contrast-enhanced mammography are described.

HIV and reproductive healthcare in pregnant and postpartum HIV-infected women: adapting successful strategies.

Linkage and retention in care for many HIV-infected women in the postpartum period is suboptimal, which compromises long-term virologic suppression and the HIV Care Continuum. Efforts are needed to improve individual outcomes by addressing transitions in care. We summarize some successful strategies to engage and retain HIV-infected women in care during the postpartum period.

Disseminated Herpes Simplex Virus with Fulminant Hepatitis.

Disseminated herpes simplex virus (HSV) is a rare cause of acute fulminant liver failure. We hereby present a case series of three patients with acute disseminated HSV with necrotizing hepatitis successfully treated with a week course of acyclovir. Early empiric administration of acyclovir therapy while awaiting confirmatory tests is critical in this potentially lethal disease.

Pregnancy in a Previously Conjoined Thoracopagus Twin with a Crisscross Heart.

Background. Crisscross heart (CCH) is a complex, rare, congenital, rotational, cardiac abnormality that accounts for <0.1% of congenital heart defects (CHD). CCH is characterized by the crossing of the inflow streams of the two ventricles due to an abnormal twisting of the heart. A case of maternal CCH has not been previously reported. Case. We report a case of a primigravida with a CCH, who was separated at birth from her thoracopagus conjoined twin. Pregnancy was managed by congenital cardiology, maternal-fetal medicine, anesthesiology, and obstetrics. She underwent a 39-week vaginal delivery without maternal or neonatal complication. Conclusion. A successful term pregnancy outcome was achieved in a patient with CCH using a multidisciplinary approach to address her cardiac condition.

Necrotizing Soft Tissue Infection Occurring after Exposure to Mycobacterium marinum.

Cutaneous infections caused by Mycobacterium marinum have been attributed to aquarium or fish exposure after a break in the skin barrier. In most instances, the upper limbs and fingers account for a majority of the infection sites. While previous cases of necrotizing soft tissue infections related to M. marinum have been documented, the importance of our presenting case is to illustrate the aggressive nature of M. marinum resulting in a persistent necrotizing soft tissue infection of a finger that required multiple aggressive wound debridements, followed by an amputation of the affected extremity, in order to hasten recovery.

The impact of penicillin skin testing on clinical practice and antimicrobial stewardship.

BACKGROUND: Penicillin skin testing (PST) is a simple and reliable way of diagnosing penicillin allergy. After being off the market for 4 years, penicilloyl-polylysine was reintroduced in 2009 as PRE-PEN. We describe the negative predictive value (NPV) of PST and the impact on antibiotic selection in a sample of hospitalized patients with a reported history of penicillin allergy. METHODS: We introduced a quality improvement process at our 861-bed tertiary care hospital that used PST to guide antibiotic usage in patients with a history consistent with an immunoglobulin E (IgE)-mediated reaction to penicillin. Subjects with a negative PST were then transitioned to a ß-lactam agent for the remainder of their therapy. NPV of skin testing was established at 24-hour follow-up. We are reporting the result of 146 patients tested between March 2012 and July 2012. RESULTS: A total of 146 patients with a history of penicillin allergy and negative PST were treated with ß-lactam antibiotics. Of these, only 1 subject experienced an allergic reaction to the PST. The remaining 145 patients tolerated a full course of ß-lactam therapy without an allergic response, giving the PST a 100% NPV. We estimated that PST-guided antibiotic alteration for these patients resulted in an estimated annual savings of $82,000. CONCLUSION: Patients with a history of penicillin allergy who have a negative PST result are at a low risk of developing an immediate-type hypersensitivity reaction to ß-lactam antibiotics. The increased use of PST may help improve antibiotic stewardship in the hospital setting.

A case of Exophiala oligosperma successfully treated with voriconazole.

Exophiala oligosperma is an uncommon pathogen associated with human infections, predominantly in immunocompromised hosts. Case reports of clinical infections related to E. oligosperma have been limited to 6 prior publications, all of which have shown limited susceptibility to conventional antifungal therapies, including amphotericin B, itraconazole, and fluconazole. We describe the first case of an E. oligosperma induced soft-tissue infection successfully treated with a 3-month course of voriconazole without persisting lesions.

Group A streptococcal infections in obstetrics and gynecology.

Group A streptococcal (GAS) infections continue to be an infrequent, but potentially lethal infections in women despite the victory over childbed fever in the 1800s. Invasive group A streptococcal infection still causes 40% of septic deaths among patients with postpartum endometritis, necrotizing fasciitis, and toxic shock syndrome. Many times symptoms and signs of this infection are nonspecific, but laboratory evaluation can suggest serious infection. The prudent combination of antibiotic and surgical therapy can be lifesaving.