COVID-19 in obstetrics 2020: the experience at a New York City medical center.

The global spread of the SARS-CoV-2 virus during the early months of 2020 was rapid and exposed vulnerabilities in health systems throughout the world. Obstetric SARS-CoV-2 disease was discovered to be largely asymptomatic carriage but included a small rate of severe disease with rapid decompensation in otherwise healthy women. Higher rates of hospitalization, Intensive Care Unit (ICU) admission and intubation, along with higher infection rates in minority and disadvantaged populations have been documented across regions. The operational gymnastics that occurred daily during the Covid-19 emergency needed to be translated to the obstetrics realm, both inpatient and ambulatory. Resources for adaptation to the public health crisis included workforce flexibility, frequent communication of operational and protocol changes for evaluation and management, and application of innovative ideas to meet the demand.

Diagnostic accuracy of isolated clubfoot in twin compared to singleton gestations.

Background Our objective was to determine the predictive value of the prenatal diagnosis of isolated clubfoot in twin gestations compared to singleton gestations. Methods A prospectively entered ultrasound database was reviewed for all pregnancies scanned at our institution from 2002 to 2014. Cases of suspected clubfoot were identified. Neonates with associated anomalies or aneuploidy, and patients who delivered at other institutions were excluded. Neonatal charts were reviewed for the confirmation of clubfoot. The chi-squared (χ2) test, Fisher's exact test and the Mann-Whitney U test were used in the analysis, with p < 0.05 considered significant. Results Of those women who had prenatal ultrasound and subsequently delivered at our hospital, 84 pregnancies had isolated clubfoot suspected in the antenatal period. Of these pregnancies, 20 were twin gestations and 64 were singleton gestations. Overall, 51/84 (60.7%) pregnancies had clubfoot confirmed during the neonatal period. Of the twin pregnancies, only 35% (7/20) had a confirmed diagnosis of clubfoot at birth compared to 68.8% (44/64) of the singleton pregnancies (P = 0.008). Gestational age at diagnosis, breech presentation, neonatal gender, unilateral vs. bilateral clubfoot and suspicion of clubfoot in the presenting twin (Twin A) vs. the non-presenting twin (Twin B) did not correlate with an accurate diagnosis of clubfoot in twins. Conclusion False-positive prenatal diagnosis of isolated clubfoot is more common in twin gestations compared to singletons. This may be due to transient malpositioning or a result of diminished space. Obstetric providers should consider the possibility of a false-positive diagnosis and use caution when counseling patients about a prenatal suspicion for clubfoot, especially in twin gestations.

Hyponatremia associated with preeclampsia.

OBJECTIVE: The objective of our study was to evaluate the prevalence and clinical factors associated with hyponatremia in patients with preeclampsia. STUDY DESIGN: This is a descriptive study of all patients who delivered at our institution from 2013 to 2014. Patients with preeclampsia were identified from electronic medical records. Preeclampsia with and without severe features was defined using the criteria outlined in the American Congress of Obstetricians and Gynecologists Hypertension in Pregnancy guidelines. As sodium levels have been shown to be approximately 5 mEq/L lower in pregnancy, hyponatremia was defined as a sodium level <130 mEq/L. RESULTS: We identified 332 pregnancies complicated by preeclampsia, including 277 singletons and 55 twins. Hyponatremia was noted in 32 (9.7%) patients. Preeclampsia with severe features was present in the majority of patients with hyponatremia, and hyponatremia was more common in those with preeclampsia with severe features compared to those without (P<0.001). Hyponatremia also occurred more frequently in twins (P=0.001) and in older women (P=0.017). Only one patient without hyponatremia had an eclamptic seizure. CONCLUSION: Hyponatremia is not uncommon in preeclampsia, and is even more common in those with preeclampsia with severe features and twin gestations. As women with preeclampsia are at risk for hyponatremia, serum sodium should be monitored, especially in women with preeclampsia with severe features or twin gestations.

Low PAPP-A: the impact of ultrasound to evaluate fetal growth.

OBJECTIVE: Our objective was to describe utilization and impact of sonographic growth assessment in pregnancies with low pregnancy-associated plasma protein-A (PAPP-A). METHODS: Singleton pregnancies with PAPP-A ≤5th percentile and no other risk factors for fetal growth restriction from January 2011-June 2013 were included. Antepartum and delivery data were obtained by reviewing medical records. Outcomes of pregnancies referred for sonographic growth assessment were compared with those not referred for ultrasound. Fisher's exact test, chi-square analysis, and Mann-Whitney U were used for statistical comparison. RESULTS: Two hundred ninety-five patients were included. Of 285 pregnancies reaching the third trimester, 77.5% were referred for ultrasound, with the initial scan at a median gestational age of 28 weeks [26-29]. Referral for growth scans was associated with earlier gestational age at delivery and higher rates of delivery for fetal indications. Those who did not undergo growth scans were more likely to deliver a small for gestational age infant at term, 20.7% versus 35.0% (p = 0.04). There was one third-trimester fetal demise, occurring in a patient who had been undergoing growth scans. CONCLUSION: Growth scans in those with low PAPP-A were associated with delivery at earlier gestational age, with higher rates of delivery for fetal indications and lower rates of small for gestational age newborns at term. No significant differences in neonatal outcomes were observed.

Echogenic intracardiac foci: disclosure and the rate of amniocentesis in low-risk patients.

OBJECTIVE: Our objective was to determine the impact of disclosure of echogenic intracardiac focus (EIF) on the rate of amniocentesis in women who have undergone sequential testing. STUDY DESIGN: This was a retrospective study of women who had sequential testing for Down syndrome from 2009 through 2011. The Down syndrome risk was doubled in pregnancies with EIF, consistent with counseling provided to patients. In the control group Down syndrome risk was based on sequential testing. Within risk categories (1 in <250, 251-1000, 1001-5000, >5000) rates of amniocentesis with and without documented EIF were compared using Fisher exact test. RESULTS: In all, 4429 women at a median maternal age were included, including 229 with EIF (5.2%). In those at highest Down syndrome risk (1 in <250), rates of amniocentesis were similar between the 2 groups. In those at lower levels of risk, the rate of amniocentesis was significantly higher following disclosure of EIF compared to pregnancies without EIF at similar levels of risk. CONCLUSION: Except for those at highest risk, rates of invasive testing were significantly higher in pregnancies with isolated EIF vs those at comparable risk.

Time restricted feeding modifies leukocyte responsiveness and improves inflammation outcome.

Time restricted eating, the dietary approach limiting food intake to a maximal 10-hour period of daytime is considered beneficial in metabolic dysfunctions, such as obesity and diabetes. Rhythm of food intake and parallel changes in serum nutrient levels are also important entrainment signals for the circadian clock, particularly in tissues involved in metabolic regulation. As both the metabolic state and the circadian clock have large impact on immune functions, we investigated in mice whether time restricted feeding (TRF) affects systemic inflammatory potential. TRF slackened the symptoms in K/BxN serum-transfer arthritis, an experimental model of human autoimmune joint inflammation. Compared to ad libitum conditions TRF reduced the expression of inflammatory mediators in visceral adipose tissue, an integrator and coordinator of metabolic and inflammatory processes. Furthermore, TRF strengthened the oscillation of peripheral leukocyte counts and alongside decreased the pool of both marginated and tissue leukocytes. Our data suggest that the altered leukocyte distribution in TRF mice is related to the attenuated expression of adhesion molecules on the surface of neutrophils and monocytes. We propose that TRF modifies both rhythm and inflammatory potential of leukocytes which contribute to the milder reactivity of the immune system and therefore time-restricted eating could serve as an effective complementary tool in the therapy of autoinflammatory processes.

Household contact investigation for the detection of active tuberculosis and latent tuberculosis: A comprehensive evaluation in two high-burden provinces in Iran.

BACKGROUND: Systematic evaluation of household contacts of persons with pulmonary tuberculosis (TB) in low- and middle-income countries is recommended by the World Health Organization (WHO). This study recruited adult household contacts of diagnosed TB patients in two high burden provinces of Iran to estimate the prevalence and incidence of active disease and latent TB infection (LTBI) among individuals exposed to TB cases. METHODS: We conducted a cohort study among adults in household contact with a pulmonary TB index case. All subjects were assessed for active disease through evaluation of symptoms. Tuberculin skin test (TST) and QuantiFERON®-TB Gold Plus (QFT-Plus) were used to define LTBI. These tests were performed at the time of the index TB case diagnosis and repeated if the previous result was negative, at three-, 12-, and 18-months post recruitment. In addition, interferon-γ-induced protein-10 (IP-10) concentrations were measured in QFT-Plus supernatants for all participants three months after diagnosing the index case. RESULTS: A total of 451 individuals who had close contact with 95 active TB patients were enrolled in this study. Five (1.1%) contacts were diagnosed with active TB and 285 (63.2%) were identified with LTBI during our study. The incidence rate of LTBI among adult household contacts of TB index cases was 0.44 per person per year. CONCLUSION: The overall rate of LTBI was high. Systematic screening of all household contacts of pulmonary TB should be expanded in Iran to make the timely achievement of the global end TB strategy feasible.

Multicentre study of the main carbapenem resistance mechanisms in important members of the Enterobacteriaceae family in Iran.

Resistance to carbapenems has been increasingly reported from the Enterobacteriaceae family, with different mechanisms in different geographic parts of the world. This study investigated the mechanisms of carbapenem resistance in Escherichia coli, Klebsiella pneumoniae and Enterobacter spp. carried out as a multicentre study (n = 10). All third-generation cephalosporin-resistant E. coli, K. pneumoniae and Enterobacter spp. that had been recovered from the selected provinces were included. Modified Hodge test and Carba NP test were done as a phenotypical method for detection of carbapenemase; the most common carbapenemase was detected by PCR. We evaluated the presence of an active efflux pump by using cyanide 3-chlorophenylhydrazone. Overexpression of AcrA/B and presence of OqxAB was detected by real-time PCR and conventional PCR respectively. Microorganisms in this study included 58 E. coli, 95 K. pneumoniae and 60 Enterobacter spp. Modified Hodge test showed a sensitivity of 41% and a specificity of 83%, and the Carba NP test showed a sensitivity of 26% and a specificity of 92% for detection of carbapenemase. OXA-48 was the most frequently detected carbapenemase, followed by NDM-1. Thirty-nine percent and 27% of positive cyanide 3-chlorophenylhydrazone test organisms included active AcrA/B and OqxAB efflux pumps respectively. The result showed the Carba NP test was more specific than MHT. Data confirmed the involvement of AcrA/B and OqxAB efflux pump as a carbapenem resistance mechanism in selected bacteria. Similar to other reports from the Middle East, we found OXA-48 and NDM-1 to be the most frequent carbapenemase.

Reductions in commuting mobility correlate with geographic differences in SARS-CoV-2 prevalence in New York City.

SARS-CoV-2-related mortality and hospitalizations differ substantially between New York City neighborhoods. Mitigation efforts require knowing the extent to which these disparities reflect differences in prevalence and understanding the associated drivers. Here, we report the prevalence of SARS-CoV-2 in New York City boroughs inferred using tests administered to 1,746 pregnant women hospitalized for delivery between March 22nd and May 3rd, 2020. We also assess the relationship between prevalence and commuting-style movements into and out of each borough. Prevalence ranged from 11.3% (95% credible interval [8.9%, 13.9%]) in Manhattan to 26.0% (15.3%, 38.9%) in South Queens, with an estimated city-wide prevalence of 15.6% (13.9%, 17.4%). Prevalence was lowest in boroughs with the greatest reductions in morning movements out of and evening movements into the borough (Pearson R = -0.88 [-0.52, -0.99]). Widespread testing is needed to further specify disparities in prevalence and assess the risk of future outbreaks.

Cerebrospinal Fluid Penetration and Combination Therapy of Entrectinib for Disseminated ROS1/NTRK-Fusion Positive Pediatric High-Grade Glioma.

Targeting oncogenic fusion-genes in pediatric high-grade gliomas (pHGG) with entrectinib has emerged as a highly promising therapeutic approach. Despite ongoing clinical studies, to date, no reports on the treatment of cerebrospinal fluid (CSF) disseminated fusion-positive pHGG exist. Moreover, clinically important information of combination with other treatment modalities such as intrathecal therapy, radiotherapy and other targeted agents is missing. We report on our clinical experience of entrectinib therapy in two CSF disseminated ROS1/NTRK-fusion-positive pHGG cases. Combination of entrectinib with radiotherapy or intrathecal chemotherapy appears to be safe and has the potential to act synergistically with entrectinib treatment. In addition, we demonstrate CSF penetrance of entrectinib for the first time in patient samples suggesting target engagement even upon CSF dissemination. Moreover, in vitro analyses of two novel cell models derived from one case with NTRK-fusion revealed that combination therapy with either a MEK (trametinib) or a CDK4/6 (abemaciclib) inhibitor synergistically enhances entrectinib anticancer effects. In summary, our comprehensive study, including clinical experience, CSF penetrance and in vitro data on entrectinib therapy of NTRK/ROS1-fusion-positive pHGG, provides essential clinical and preclinical insights into the multimodal treatment of these highly aggressive tumors. Our data suggest that combined inhibition of NTRK/ROS1 and other therapeutic vulnerabilities enhances the antitumor effect, which should be followed-up in further preclinical and clinical studies.

Prevalence of oropharyngeal colonization by Haemophilus influenzae type b in Iranian children.

Healthy carriers of Haemophilus influenzae type b (Hib) play an important role in the spread of invasive disease. The aim of this study was to assess the need for Hib vaccination in Iranian children by estimating the prevalence of Hib oropharyngeal colonization among children in Tehran. Cultures were prepared from oropharyngeal swabs of 1000 children in 25 day-care centres in Tehran from October 2005 to March 2006. The prevalence of Hib carriers was 7.6%, similar to other developing countries prior to inoculation with the conjugate Hib vaccine. We recommend Hib vaccination be included in the Iranian national programme of immunization.

Clinical characteristics and molecular epidemiology of children with meningitis in Tehran, Iran: a prospective study.

The molecular epidemiology of meningitis in children is unclear in Iran, and data are scarce. We aimed to characterize its clinical and paraclinical features as well as to determine the distribution of genotype/capsular types of common bacterial meningitis agents in children in Iran. All children suspected to have meningitis aged 4 days to 15 years were enrolled onto a prospective cross-sectional study from January 2015 to September 2017. Diagnostic values of clinical features, cerebrospinal fluid and serum parameters were evaluated independently and in combination with each other by multivariate logistic regression to develop a diagnostic rule. Genotype/capsular types of all the isolates were determined by targeting serotype-specific genes with uniplex or multiplex PCR. Among 119 patients suspected of having meningitis, 43 had bacterial meningitis, 19 aseptic and one tuberculous; and there were 56 nonmeningitis cases (NMC). Presentation of four features at the same time-cerebrospinal fluid white blood cell count, protein, polymorphonuclear leukocytes and serum C-reactive protein-revealed 100% sensitivity and 86.4% specificity for diagnosis of bacterial meningitis. Haemophilus influenzae type b (60%), Streptococcus pneumoniae serotype 3 (28.5%) and Neisseria meningitidis B (63.5%) were the most prevalent serotypes. This study demonstrated that a well-designed combination of clinical and paraclinical features is useful, but these combinations are not good enough to be relied on as stand-alone exclusionary tests for the diagnosis of bacterial meningitis. In addition, public immunization of infants with the most prevalent bacterial meningitis serotypes is recommended.

Vasospasm in traumatic brain injury.

Given the large societal burden from morbidity and mortality associated with traumatic brain injury (TBI), this disease entity has been the focus of extensive research over the past decades. Since primary injury in TBI is preventable whereas secondary injury is treatable, most of the research effort has been targeted at identifying factors that contribute to secondary injury and ways to minimize their deleterious effects. Whether post-traumatic vasospasm is one such factor is open for debate. Although radiological or anatomical vasospasm following head injury has been repeatedly demonstrated using various diagnostic techniques, its clinical significance is still under investigation. At the present time, no proven treatment regimen aimed specifically at decreasing the potential detrimental effects of post-traumatic vasospasm exists. Although calcium channel blockers have shown some promise in decreasing death or severe disability in those with traumatic subarachnoid haemorrhage, whether their mechanism is by minimizing vasospasm is open to speculation. Therefore, currently, vigilant diagnostic surveillance, including serial head CT's and the prevention of secondary brain damage due to hypotension, hypoxia, and intracranial hypertension, may be more cost effective than attempting to minimize post-traumatic vasospasm.

Isolated Fetal Cardiac Abnormalities: Are They Really Isolated?

Objective To determine the rate of unsuspected noncardiac abnormalities in newborns suspected to have isolated cardiac abnormalities in the second trimester. Study Design A review of the ultrasound database from the Weill Cornell Medical Center identified fetuses with a suspected cardiac abnormality from January 2006 to November 2016. Cases with prenatally suspected noncardiac structural abnormalities, abnormal fetal or neonatal karyotype or microarray, and those who delivered at an outside institution or underwent abortion were excluded. Neonatal records were reviewed to confirm prenatal findings and to identify anomalies not suspected in the second trimester. Results Sixty-eight live births met the inclusion criteria. Five newborns (7.4%) had major abnormalities not identified in the second trimester. Three newborns had an imperforate anus. One newborn had left hydronephrosis and absent right lung, and one had hemifacial microsomia and fused ribs. All five newborns with unsuspected anomalies were in the group with suspected conotruncal anomalies, with a 11.9% rate of unsuspected anomalies versus 0% in those with nonconotruncal cardiac anomalies ( p = 0.15). Conclusion Patients with a suspected isolated fetal cardiac anomaly on ultrasound should be aware of the possibility of other major structural abnormalities, especially in cases of conotruncal cardiac anomalies.

Preterm delivery in triplet pregnancies.

PURPOSE: The purpose of this study is to assess the rate of spontaneous preterm birth (SPTB) versus indicated preterm birth (IPTB) in triplet pregnancies and determine factors associated with these outcomes. MATERIALS AND METHODS: This is a review of triplet pregnancies delivering at our institution from 2003 to 2015. Patients delivering prior to 24 weeks gestational age (GA) were excluded. SPTB included cases of preterm labor or preterm premature rupture of membranes <37 weeks. IPTB was defined as deliveries <37 weeks for maternal or fetal complications. RESULTS: Of 80 triplet pregnancies, 18 (22.5%) were not complicated by SPTB or IPTB and reached their scheduled delivery date. In the remaining 62 pregnancies, IPTB occurred in 31 patients and SPTB in 31 patients. Parity was the only significant factor associated with reaching a scheduled delivery, with 56.3% of parous women reaching a scheduled delivery versus 14.1% of nulliparous women (p = 0.001). There were no significant differences in maternal age, parity, chorionicity, or use of ART between the SPTB and ITPB groups. CONCLUSIONS: While the majority of our triplet patients delivered preterm, IPTB occurred as frequently as SPTB in our population. Parous women were significantly less likely to experience SPTB or to require preterm delivery for maternal or fetal indications.

Perception and regulatory principles of microbial growth control.

Fast growth represents an effective strategy for microbial organisms to survive in competitive environments. To accomplish this task, cells must adapt their metabolism to changing nutrient conditions in a way that maximizes their growth rate. However, the regulation of the growth related metabolic pathways can be fundamentally different among microbes. We therefore asked whether growth control by perception of the cell's intracellular metabolic state can give rise to higher growth than by direct perception of extracellular nutrient availability. To answer this question, we created a simplified dynamical computer model of a cellular metabolic network whose regulation was inferred by an optimization approach. We used this model for a competing species experiment, where a species with extracellular nutrient perception competes against one with intracellular nutrient perception by evaluating their respective average growth rate. We found that the intracellular perception is advantageous under situations where the up and down regulation of pathways cannot follow the fast changing nutrient availability in the environment. In this case, optimal regulation ignores any other nutrients except the most preferential ones, in agreement with the phenomenon of catabolite repression in prokaryotes. The corresponding metabolic pathways remain activated, despite environmental fluctuations. Therefore, the cell can take up preferential nutrients as soon as they are available without any prior regulation. As a result species that rely on intracellular perception gain a relevant fitness advantage in fluctuating nutrient environments, which enables survival by outgrowing competitors.

Prevalence of oropharyngeal colonization by Haemophilus influenzae type b in Iranian children

Healthy carriers of Haemophilus influenzae type b [Hib] play an important role in the spread of invasive disease. The aim of this study was to assess the need for Hib vaccination in Iranian children by estimating the prevalence of Hib oropharyngeal colonization among children in Tehran. Cultures were prepared from oropharyngeal swabs of 1000 children in 25 day-care centres in Tehran from October 2005 to March 2006. The prevalence of Hib carriers was 7.6%, similar to other developing countries prior to inoculation with the conjugate Hib vaccine. We recommend Hib vaccination be included in the Iranian national programme of immunization