Publications by authors named "Rose Du"

194 Publications

Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 10;1867(10):166198. Epub 2021 Jun 10.

Fetal and Perinatal Medicine and Surgery Unit, Medical and Surgical Department of Fetus, Newborn and Infant - "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy. Electronic address:

Some maternal infections, contracted before or during pregnancy, can be transmitted to the fetus, during gestation (congenital infection), during labor and childbirth (perinatal infection) and through breastfeeding (postnatal infection). The agents responsible for these infections can be viruses, bacteria, protozoa, fungi. Among the viruses most frequently responsible for congenital infections are Cytomegalovirus (CMV), Herpes simplex 1-2, Herpes virus 6, Varicella zoster. Moreover Hepatitis B and C virus, HIV, Parvovirus B19 and non-polio Enteroviruses when contracted during pregnancy may involve the fetus or newborn at birth. Recently, new viruses have emerged, SARS-Cov-2 and Zika virus, of which we do not yet fully know the characteristics and pathogenic power when contracted during pregnancy. Viral infections in pregnancy can damage the fetus (spontaneous abortion, fetal death, intrauterine growth retardation) or the newborn (congenital anomalies, organ diseases with sequelae of different severity). Some risk factors specifically influence the incidence of transmission to the fetus: the timing of the infection in pregnancy, the order of the infection, primary or reinfection or chronic, the duration of membrane rupture, type of delivery, socio-economic conditions and breastfeeding. Frequently infected neonates, symptomatic at birth, have worse outcomes than asymptomatic. Many asymptomatic babies develop long term neurosensory outcomes. The way in which the virus interacts with the maternal immune system, the maternal-fetal interface and the placenta explain these results and also the differences that are observed from time to time in the fetal‑neonatal outcomes of maternal infections. The maternal immune system undergoes functional adaptation during pregnancy, once thought as physiological immunosuppression. This adaptation, crucial for generating a balance between maternal immunity and fetus, is necessary to promote and support the pregnancy itself and the growth of the fetus. When this adaptation is upset by the viral infection, the balance is broken, and the infection can spread and lead to the adverse outcomes previously described. In this review we will describe the main viral harmful infections in pregnancy and the potential mechanisms of the damages on the fetus and newborn.
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http://dx.doi.org/10.1016/j.bbadis.2021.166198DOI Listing
June 2021

Neonatal SARS-CoV-2 Infection: Practical Tips.

Pathogens 2021 May 17;10(5). Epub 2021 May 17.

Neonatal Intensive Care Unit and Neonatal pathology Unit, Policlinico San Matteo IRCCS Foundation, 27100 Pavia, Italy.

The recent viral pandemic in Wuhan, Hubei, China has led to the identification of a new species of beta-coronavirus, able to infect humans, the 2019-nCoV, later named SARS-CoV-2. SARS-CoV-2 causes a clinical syndrome named COVID-19, which presents with a spectrum of symptoms ranging from mild upper respiratory tract infection to severe pneumonia, with acute respiratory distress syndrome and frequent death. All age groups are susceptible to the infection, but children, especially infants, seem to be partially spared, having a more favorable clinical course than other age groups. There is currently no clear evidence showing vertical transmission and intrauterine SARS-CoV-2 infection in fetuses of women developing COVID-19 pneumonia in late pregnancy, and even if transmission is possible, the SARS-CoV2 positivity of the mother does not require delivery by caesarean section, does not contraindicate the management of the infant in rooming-in and allows breastfeeding. This review provides an overview on the biology of the virus, on the pathogenesis of the infection, with particular attention to pregnancy and neonatal age, on the clinical presentation of infection in newborns and young infants and summarizes the international recommendations currently available on the clinical care of neonates with SARS-CoV2 infection or at risk of catching the virus. The main objective of the review is to provide an update especially focused to the clinical management of COVID-19 infection in the perinatal and neonatal age.
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http://dx.doi.org/10.3390/pathogens10050611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157198PMC
May 2021

Direct vs Indirect Revascularization in a North American Cohort of Moyamoya Disease.

Neurosurgery 2021 May 6. Epub 2021 May 6.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: In adults with ischemic moyamoya disease (MMD), the efficacy of direct vs indirect revascularization procedures remains a matter of debate.

Objective: To investigate the outcomes of ischemic MMD in a North American cohort treated by direct and indirect revascularizations.

Methods: We retrospectively reviewed medical records of adult patients with MMD with ischemic presentation from 1984 to 2018 at the Brigham and Women's Hospital and Massachusetts General Hospital who underwent either direct or indirect bypasses. Early postoperative events and outcome at more than 6 mo postoperatively were evaluated using multivariable logistic regression analyses. Multivariable Cox proportional hazards regression analyses were used to evaluate delayed ischemic and hemorrhagic events. Analyses were performed per hemisphere.

Results: A total of 95 patients with MMD and 127 hemispheres were included in this study. A total of 3.5% and 8.6% of patients had early surgical complications in the direct and indirect bypass cohorts, respectively (P = .24). Hemispheres with direct bypasses had fewer long-term ischemic and hemorrhagic events at latest follow-up (adjusted hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.058-0.63, P = .007; median follow-up 4.5 [interquartile range, IQR 1-8] yr). There was no difference between the direct and indirect bypass groups when the endpoint was limited to infarction and hemorrhage only (P = .12). There was no difference in outcome (modified Rankin Scale [mRS] ≥ 3) between the 2 cohorts (P = .92).

Conclusion: There was no difference in early postoperative events, long-term infarction or hemorrhage, or clinical outcome between direct and indirect revascularization. However, there was a significant decrease in all ischemic and hemorrhagic events combined in direct revascularizations compared to indirect revascularizations.
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http://dx.doi.org/10.1093/neuros/nyab156DOI Listing
May 2021

CSF lipocalin-2 increases early in subarachnoid hemorrhage are associated with neuroinflammation and unfavorable outcome.

J Cereb Blood Flow Metab 2021 May 5:271678X211012110. Epub 2021 May 5.

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.

Lipocalin-2 mediates neuro-inflammation and iron homeostasis in vascular injuries of the central nervous system (CNS) and is upregulated in extra-CNS systemic inflammation. We postulate that cerebrospinal fluid (CSF) and blood lipocalin-2 levels are associated with markers of inflammation and functional outcome in subarachnoid hemorrhage (SAH). We prospectively enrolled 67 SAH subjects, serially measured CSF and plasma lipocalin-2, matrix metallopeptidase 9 (MMP-9), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) on post-SAH days 1-5 and assessed outcome by modified Rankin Scale (mRS) every 3 months. Unfavorable outcome is defined as mRS > 2. Twenty non-SAH patients undergoing lumbar drain trial were enrolled as controls. Lipocalin-2 was detectable in the CSF and significantly higher in SAH compared to controls (p < 0.0001). Higher CSF LCN2 throughout post-SAH days 1-5 was associated with unfavorable outcome at 3 (p = 0.0031) and 6 months (p = 0.014). Specifically, higher CSF lipocalin-2 on post-SAH days 3 (p = 0.036) and 5 (p = 0.016) were associated with unfavorable 3-month outcome. CSF lipocalin-2 levels positively correlated with CSF IL-6, TNF-α and MMP-9 levels. Higher plasma lipocalin-2 levels over time were associated with worse 6-month outcome. Additional studies are required to understand the role of lipocalin-2 in SAH and to validate CSF lipocalin-2 as a potential biomarker for SAH outcome.
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http://dx.doi.org/10.1177/0271678X211012110DOI Listing
May 2021

Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease.

J Med Virol 2021 Apr 14. Epub 2021 Apr 14.

Neonatal Intensive Care Unit, Department of Medical and Surgical Neonatology, "Bambino Gesù" Children's Hospital IRCCS, Rome, Italy.

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.
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http://dx.doi.org/10.1002/jmv.27016DOI Listing
April 2021

Invasive Infections in Neonates after Major Surgery: Current Evidence and New Directions.

Pathogens 2021 Mar 9;10(3). Epub 2021 Mar 9.

Neonatal Intensive Care Unit, Medical and Surgical Department of Fetus, Newborn and Infant, "Bambino Gesù" Children's Hospital IRCCS, 00165 Rome, Italy.

Infections represent a serious health problem in neonates. Invasive infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment.
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http://dx.doi.org/10.3390/pathogens10030319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999498PMC
March 2021

Tobacco use and age are associated with different morphologic features of anterior communicating artery aneurysms.

Sci Rep 2021 Feb 26;11(1):4791. Epub 2021 Feb 26.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.

We present a cohort of patients with anterior communicating artery (ACoA) aneurysms to investigate morphological characteristics and clinical factors associated with rupture of the aneurysms. 505 patients with ACoA aneurysms were identified at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016, with available CT angiography (CTA). Three-dimensional (3D) reconstructions were performed to evaluate aneurysmal morphologic features, including location, projection, irregularity, the presence of daughter dome, height, height/width ratio, and relationships between surrounding vessels. Patient risk factors assessed included patient age, sex, tobacco use, alcohol use, and family history of aneurysms and aneurysmal subarachnoid hemorrhage. Logistic regression was used to build a predictive ACoA score for rupture. Morphologic features associated with ruptured ACoA aneurysms were the presence of a daughter dome (OR 21.4, 95% CI 10.6-43.1), smaller neck diameter (OR 0.55, 95% CI 0.42-0.71), larger aspect ratio (OR 3.57, 95% CI 2.05-6.24), larger flow angle (OR 1.03, 95% CI 1.02-1.05), and smaller ipsilateral A2-ACoA angle (OR 0.98, 95% CI 0.97-1.00). Tobacco use was predominantly associated with morphological factors intrinsic to the aneurysm that were associated with rupture while younger age was also associated with morphologic features extrinsic to the aneurysm that were associated with rupture. The ACoA score had good predictive capacity for rupture with AUC = 0.92 using the 0.632 bootstrap cross-validation for correction of overfitting bias. Ruptured ACoA aneurysms were associated with morphological features that are simple to assess using a simple scoring system. Tobacco use and younger age were predominantly associated with intrinsic and extrinsic morphological features characteristic of rupture, respectively.
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http://dx.doi.org/10.1038/s41598-021-84315-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910488PMC
February 2021

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

J Neurointerv Surg 2021 Feb 25. Epub 2021 Feb 25.

Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.

Objective: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.

Methods: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.

Results: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.

Conclusions: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.
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http://dx.doi.org/10.1136/neurintsurg-2020-017109DOI Listing
February 2021

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas.

Neurosurgery 2021 May;88(6):1111-1120

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial.

Objective: To compare the outcomes of observation versus intervention for low-grade dAVFs.

Methods: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up.

Results: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively.

Conclusion: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.
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http://dx.doi.org/10.1093/neuros/nyab024DOI Listing
May 2021

Time to Positivity of Blood Cultures Could Inform Decisions on Antibiotics Administration in Neonatal Early-Onset Sepsis.

Antibiotics (Basel) 2021 Jan 28;10(2). Epub 2021 Jan 28.

Neonatology Unit, Department of Woman and Child Health and Public Health-Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, 00168 Rome, Italy.

(1) Background: Empirical antibiotics for suspected neonatal early-onset sepsis are often prolonged administered, even in the absence of clinical signs of infection, while awaiting the blood cultures results. The C-reactive protein is widely used to guide antibiotic therapy, although its increase in the first hours of life is not always evidence of infection. The aim of this study was to evaluate the time to positivity (TTP) of blood cultures (BC) that develop pathogens in our population of neonates and determine whether TTP could safely inform the decisions on empirical antibiotic discontinuation in neonatal early-onset sepsis and reduce the use of unnecessary antibiotics. (2) Methods: We retrospectively collected data of all newborns ≥ 34 weeks admitted to the Neonatal Intermediate-Care Unit at Policlinico "A. Gemelli" University Hospital (Rome, Italy) from 2014 to 2018, with suspected early-onset sepsis (EOS). The TTP was the time in hours from the first BC inoculation to the bacterial growth. We defined as positive BC only those with a pathogenic organism. (3) Results: In total, 103 out of 20,528 infants born in the five-year study period were admitted to our Neonatal Intermediate-Care Unit because of a suspected EOS and enrolled into the study. The mean TTP of pathogenic organisms was 17.7 ± 12.5 h versus 80.5 ± 55.8 h of contaminants ( 0.00). We found ten positive BCs. The TTP of BC was lower than 12, 36, and 48 h in 80%, 90%, and 100% of cases, respectively. CRP levels on admission were similar in infants with a positive and negative BC ( = 0.067). The discontinuation of therapy in asymptomatic infants 48 h after initiation would have resulted in a saving of 217 days of antibiotics (31.1% of total days administered). (4) Conclusion: From our data, the TTP of blood cultures that develop pathogens is less than 48 h in 100% of cases. Therefore, in late preterm and full-term infants with suspected EOS, stopping empiric antibiotics 48 h after initiation may be a safe practice to reduce unnecessary antibiotic use, when blood cultures are negative and infants asymptomatic.
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http://dx.doi.org/10.3390/antibiotics10020123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910918PMC
January 2021

Morphological variables associated with ruptured basilar tip aneurysms.

Sci Rep 2021 Jan 28;11(1):2526. Epub 2021 Jan 28.

Department of Neurosurgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.

Morphological factors of intracranial aneurysms and the surrounding vasculature could affect aneurysm rupture risk in a location specific manner. Our goal was to identify image-based morphological parameters that correlated with ruptured basilar tip aneurysms. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 200 patients with basilar tip aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were evaluated. We examined aneurysm wall irregularity, the presence of daughter domes, hypoplastic, aplastic or fetal PCoAs, vertebral dominance, maximum height, perpendicular height, width, neck diameter, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. In multivariable analysis, presence of a daughter dome, aspect ratio, and larger flow angle were significantly associated with rupture status. We also introduced two new variables, diameter size ratio and parent-daughter angle ratio, which were both significantly inversely associated with ruptured basilar tip aneurysms. Notably, multivariable analyses also showed that larger diameter size ratio was associated with higher Hunt-Hess score while smaller flow angle was associated with higher Fisher grade. These easily measurable parameters, including a new parameter that is unlikely to be affected by the formation of the aneurysm, could aid in screening strategies in high-risk patients with basilar tip aneurysms. One should note, however, that the changes in parameters related to aneurysm morphology may be secondary to aneurysm rupture rather than causal.
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http://dx.doi.org/10.1038/s41598-021-81364-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844275PMC
January 2021

Treatment of Subarachnoid Hemorrhage-associated Delayed Cerebral Ischemia With Milrinone: A Review and Proposal.

J Neurosurg Anesthesiol 2021 Jul;33(3):195-202

Neurological Intensive Care Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage continues to be associated with high levels of morbidity and mortality. This complication had long been thought to occur secondary to severe cerebral vasospasm, but expert opinion now favors a multifactorial etiology, opening the possibility of new therapies. To date, no definitive treatment option for DCI has been recommended as standard of care, highlighting a need for further research into potential therapies. Milrinone has been identified as a promising therapeutic agent for DCI, possessing a mechanism of action for the reversal of cerebral vasospasm as well as potentially anti-inflammatory effects to treat the underlying etiology of DCI. Intra-arterial and intravenous administration of milrinone has been evaluated for the treatment of DCI in single-center case series and cohorts and appears safe and associated with improved clinical outcomes. Recent results have also brought attention to the potential outcome benefits of early, more aggressive dosing and titration of milrinone. Limitations exist within the available data, however, and questions remain about the generalizability of results across a broader spectrum of patients suffering from DCI. The development of a standardized protocol for milrinone use in DCI, specifically addressing areas requiring further clarification, is needed. Data generated from a standardized protocol may provide the impetus for a multicenter, randomized control trial. We review the current literature on milrinone for the treatment of DCI and propose a preliminary standardized protocol for further evaluation of both safety and efficacy of milrinone.
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http://dx.doi.org/10.1097/ANA.0000000000000755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192346PMC
July 2021

Geometric variations associated with posterior communicating artery aneurysms.

J Neurointerv Surg 2021 Jan 21. Epub 2021 Jan 21.

Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA

Background: Hemodynamic stress, conditioned by the morphology of the surrounding vasculature, plays an important role in aneurysm formation. Our goal was to identify image-based location-specific parameters that are associated with posterior communicating artery (PCoA) aneurysms.

Methods: Three-dimensional morphological parameters obtained from CT angiography or digital subtraction angiography from 187 patients with unilateral PCoA aneurysms, diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. In order to control for genetic and clinical risk factors, we chose the contralateral unaffected PCoA as a control group. We examined diameters and angles of the surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small aneurysms (≤5 mm) only and an unmatched analysis of 432 PCoA aneurysms and 197 control patients without PCoA aneurysms were also performed.

Results: In a multivariable conditional logistic regression model we showed that smaller diameter size ratio (OR 1.45×10, 95% CI 1.12×10 to 1.88×10) and larger daughter-daughter angle (OR 1.04, 95% CI 1.02 to 1.07) were significantly associated with PCoA aneurysm presence after correcting for other variables. In subgroup analyses of small aneurysms (≤5 mm) and in an unmatched analysis the significance and direction of these results were preserved.

Conclusions: Larger daughter-daughter angles and smaller diameter size ratio are significantly associated with the presence of PCoA aneurysms. These simple parameters can be utilized to guide the risk assessment for the formation of PCoA aneurysms in high risk patients.
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http://dx.doi.org/10.1136/neurintsurg-2020-017062DOI Listing
January 2021

Vascular Geometry Associated with Anterior Communicating Artery Aneurysm Formation.

World Neurosurg 2021 02 9;146:e1318-e1325. Epub 2020 Dec 9.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objective: To identify clinical and morphologic risk factors correlated with anterior communicating artery (ACoA) aneurysm formation.

Methods: Three-dimensional morphologic parameters obtained from computed tomography angiography or digital subtraction angiography from 504 patients with ACoA aneurysms and 201 patients with aneurysms in other locations that were diagnosed at Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 were evaluated. The presence of hypoplastic and aplastic A1 segments and diameters and angles of surrounding parent and daughter vessels were examined. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses for small (≤3 mm) aneurysms only were also performed.

Results: Aplastic and hypoplastic A1 segments were more common in the ACoA group (38.9% vs. 6.5% hypoplastic and 22.2% vs. 0.5% aplastic). In multivariable analysis, the presence of a hypoplastic A1 segment was associated with ACoA aneurysms. An A2-ACoA (daughter-daughter) angle was also significantly associated with ACoA aneurysms in multivariable analysis; however, as Pearson's correlation test between aneurysm width and daughter-daughter angle was significant, the daughter-daughter angle was most likely not independently associated with aneurysm presence, but rather might have been a result of the presence of an aneurysm. Subgroup analyses of small aneurysms (≤3 mm) and of unruptured aneurysms showed similar results.

Conclusions: Our results demonstrate that of all the morphologic parameters, the presence of a hypoplastic A1 segment was the only parameter independently associated with the presence of ACoA aneurysms that was not correlated with aneurysm size and could aid as a simple screening parameter.
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http://dx.doi.org/10.1016/j.wneu.2020.11.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897254PMC
February 2021

A neonatal cluster of novel coronavirus disease 2019: clinical management and considerations.

Ital J Pediatr 2020 Dec 7;46(1):180. Epub 2020 Dec 7.

Pediatrics Unit, University Department of Pediatrics (DPUO), Bambino Gesù Children's Hospital - IRCCS, Via della Torre di Palidoro, 00050, Fiumicino, Rome, Italy.

Background: Lately, one of the major clinical and public health issues has been represented by Coronavirus disease of 2019 (COVID-19) during pregnancy and the risk of transmission of the infection from mother to child. Debate on perinatal management and postnatal care is still ongoing, principally questioning the option of the joint management of mother and child after birth and the safety of breastfeeding. According to the available reports, neonatal COVID-19 appears to have a horizontal transmission and seems to be paucisymptomatic or asymptomatic, compared to older age groups. The aim of this work is to describe a cluster of neonatal COVID-19 and discuss our experience, with reference to current evidence on postnatal care and perinatal management.

Methods: This is a retrospective observational case series of five mother-child dyads, who attended the Labor and Delivery Unit of a first-level hospital in Italy, in March 2020. Descriptive statistics for continuous variables consisted of number of observations, mean and the range of the minimum and maximum values.

Results: Five women and four neonates tested positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In one case, the mother-child dyad was separated and the neonate remained negative on two consecutive tests. Two positive neonates developed symptoms, with a predominant involvement of the gastrointestinal tract. Blood tests were unremarkable, except for a single patient who developed mild neutropenia. No complications occurred.

Conclusions: We agree that the decision on whether or not to separate a positive/suspected mother from her child should be made on an individual basis, taking into account the parent's will, clinical condition, hospital logistics and the local epidemiological situation. In conformity with literature, in our study, affected neonates were asymptomatic or paucisymptomatic. Despite these reassuring findings, a few cases of severe presentation in the neonatal population have been reported. Therefore, we agree on encouraging clinicians to monitor the neonates with a suspected or confirmed infection.
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http://dx.doi.org/10.1186/s13052-020-00947-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720265PMC
December 2020

Expanding the spectrum of congenital myopathies: prenatal onset with extreme hyperextension of the neck.

Neurol Sci 2021 Apr 26;42(4):1549-1553. Epub 2020 Nov 26.

Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.

We describe the case of a male newborn presenting with a prenatal diagnosis of persistent hyperextension of the fetal neck and severe hypotonia and respiratory insufficiency at birth. Facial weakness, increased serum creatine kinase levels, and abnormal feeding, together with other signs, such as severe contractures, also classically associated with congenital myopathies prompted to perform a muscle biopsy showing internal rods suggestive of a possible nemaline myopathy. These findings suggest that a careful neurological examination should be performed in infants with persistent hyperextension of the fetal neck to exclude weakness and a possible underlying muscle disorder.
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http://dx.doi.org/10.1007/s10072-020-04937-xDOI Listing
April 2021

Neurodevelopmental outcomes in very preterm infants: The role of severity of Bronchopulmonary Dysplasia.

Early Hum Dev 2021 Jan 16;152:105275. Epub 2020 Nov 16.

Neonatology Unit, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario "Agostino Gemelli" IRCCS, Rome, Italy; Università Cattolica del Sacro Cuore, Rome, Italy.

Objective: Bronchopulmonary dysplasia is a chronic respiratory disease that still affects preterm neonates; its association with neurodevelopmental (ND) impairment is already known. Different studies investigated neurodevelopmental outcomes in infants with BPD, often using the old dichotomous definition (BPD vs Non-BPD). This retrospective study aims to evaluate the role of different BPD severity grades on ND outcomes at 24 months of corrected age (CA).

Methods: All preterm infants born between 2011 and 2015 in the study hospital with a gestational age (GA) ≤ 30 weeks and discharged from our NICU were included and were divided in infants with and without BPD. Infants with BPD were divided into three severity groups as defined by NICHD/NHLBI Workshop in 2001, and were compared to their Non-BPD peers, matching them according to the same GA and year of birth. At 24 months postmenstrual age, we assessed general outcomes (growth and hospital readmissions) and neurodevelopmental outcomes (motor, developmental and sensory outcomes) with a standardized assessment.

Results: We enrolled 89 patients affected by BPD of different grades of severity and a control group of 89 preterm infants without BPD. Infants with Moderate and Severe BPD showed a significantly higher corrected odds ratio (OR) for cognitive impairment compared to controls. Within the group of infants without severe disability (regarding Griffiths' scales), infants with Moderate and Severe BPD as well as infants with Mild BPD showed a significantly higher risk of a lower total Developmental Quotient (DQ) score, even after correction for confounding factors.

Conclusions: Our study evidenced that not only Severe BPD infants, but also Moderate ones showed a higher risk of overall cognitive impairment at 24 months CA. Within the group of infants without severe disability, also those with Mild BPD had lower Griffiths DQ scores than those without. This would suggest that infants with BPD, regardless of severity, warrant neurodevelopmental follow-up.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105275DOI Listing
January 2021

Surrounding vascular geometry associated with basilar tip aneurysm formation.

Sci Rep 2020 10 21;10(1):17928. Epub 2020 Oct 21.

Department of Neurosurgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, 02115, USA.

Hemodynamic stress is thought to play an important role in the formation of intracranial aneurysms, which is conditioned by the geometry of the surrounding vasculature. Our goal was to identify image-based morphological parameters that were associated with basilar artery tip aneurysms (BTA) in a location-specific manner. Three-dimensional morphological parameters obtained from CT-angiography (CTA) or digital subtraction angiography (DSA) from 207 patients with BTAs and a control group of 106 patients with aneurysms elsewhere to control for non-morphological factors, who were diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016, were evaluated. We examined the presence of hypoplastic, aplastic or fetal PCoAs, vertebral dominance, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine statistical significance. Sensitivity analyses with small (≤ 3 mm) aneurysms only and with angles excluded, were also performed. In multivariable analysis, daughter-daughter angle was directly, and parent artery diameter and diameter size ratio were inversely associated with BTAs. These results remained significant in the subgroup analysis of small aneurysms (width ≤ 3 mm) and when angles were excluded. These easily measurable and robust parameters that are unlikely to be affected by aneurysm formation could aid in risk stratification for the formation of BTAs in high-risk patients.
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http://dx.doi.org/10.1038/s41598-020-74266-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578056PMC
October 2020

Familial Predisposition and Differences in Radiographic Patterns in Spontaneous Nonaneurysmal Subarachnoid Hemorrhage.

Neurosurgery 2021 01;88(2):413-419

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Subarachnoid hemorrhage (SAH) from an intracranial aneurysmal rupture is the most common nontraumatic etiology for SAH, but up to 15% of patients with SAH have no identifiable source.

Objective: To assess familial predisposition to spontaneous nonaneurysmal SAH (naSAH) and to evaluate whether family history affects the severity of presentation and prognosis of this condition.

Methods: We conducted a retrospective analysis of all spontaneous SAH with negative digital subtraction angiography from 2004 to 2018. Patients were divided into 2 groups: patients with first- or second-degree relatives with intracranial aneurysms and patients with no family history. Univariate and multivariate regression analyses were used to study patient presentation, radiographic patterns of hemorrhage, and clinical outcome.

Results: A total of 100 patients met the inclusion criteria. There were no individuals with family history of naSAH. A total of 15 patients (15%) had at least one family member with an intracranial aneurysm, of which 12 (12%) presented as SAH. Patients without family history had a higher percentage of perimesencephalic presentation, whereas those with family history had a higher percentage of nonperimesencephalic SAH presentation (47% vs 13%, odds ratio [OR] 0.17 [95% CI 0.04, 0.81]).

Conclusion: We found a high rate of family history of intracranial aneurysms in patients who presented with naSAH. Although there was no difference in clinical outcome in patients with and without family history, there appears to be a higher percentage of nonperimesencephalic radiographic patterns of SAH in those with family history, suggesting possible different etiologies of these hemorrhages.
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http://dx.doi.org/10.1093/neuros/nyaa396DOI Listing
January 2021

Universal Screening for SARS-CoV-2 of all Human Milk Bank Samples.

J Hum Lact 2021 02 22;37(1):40-42. Epub 2020 Sep 22.

9342 Neonatal Intensive Care Unit and Human Milk Bank, Medical and Surgical Department of Fetus - Newborn - Infant, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

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http://dx.doi.org/10.1177/0890334420962074DOI Listing
February 2021

Return to Driving Is a Better Predictor of Patient Outcome Than Return to Work After Aneurysmal Subarachnoid Hemorrhage.

World Neurosurg 2020 12 20;144:e285-e295. Epub 2020 Aug 20.

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA; Department of Neurosurgery, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Objective: Return to work and driving are major rehabilitation goals for patients after an aneurysmal subarachnoid hemorrhage (aSAH). Our goal is to identify factors that may predict return to work or driving after aSAH.

Methods: Medical records of patients with aSAH were retrospectively reviewed from 2010 to 2018. Information on return to work and driving were prospectively collected. Univariate analyses were performed to assess the association between return to work or driving with patient characteristics, social factors, and admission clinical and radiographic severity. Multivariate regression models were used to evaluate return to work and driving and generate predictive models.

Results: A total of 193 patients were included, of whom 32% (62/193) resumed work and 57% (110/193) returned to driving. Median follow-up time was 3.4 years (interquartile range, 0.7-7.5 years). Return to work was associated with younger age (odds ratio [OR], 0.89; 95% CI, 0.85-0.94), lower Hunt and Hess grade (OR, 0.34; 95% CI, 0.23-0.54), and lack of seizures (OR, 0.09; 95% CI, 0.02-0.47). Return to driving was associated with younger age (OR, 0.94; 95% CI, 0.91-0.98), lower Hunt and Hess grade (OR, 0.36; 95% CI, 0.23-0.56), married status (OR, 3.4; 95% CI, 1.2-9.4), current or former smoking (OR, 3.9; 95% CI, 1.5-10.1), lack of recreational drug use (OR, 0.08; 95% CI, 0.01-0.77), and lack of seizures (OR, 0.28; 95% CI, 0.08-0.96). Admission risk factors were predictive of return to driving and return to work in the final multivariate models generated (area under the receiver operating characteristic curve 88% vs. 89%, respectively).

Conclusions: Because work may be highly dependent on complex individual and social factors, driving is a simple and more accurate assessment for an individual's status after aSAH.
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http://dx.doi.org/10.1016/j.wneu.2020.08.113DOI Listing
December 2020

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age.

Int J Mol Sci 2020 Aug 17;21(16). Epub 2020 Aug 17.

Neonatal Intensive Care Unit, Department of Medical and Surgical Neonatology, "Bambino Gesù" Children's Hospital IRCCS, 00165 Rome, Italy.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.
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http://dx.doi.org/10.3390/ijms21165898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460644PMC
August 2020

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

Am J Perinatol 2020 09 5;37(S 02):S31-S38. Epub 2020 Aug 5.

Neonatal Intensive Care Unit, IRCCS Foundation Policlinico "San Matteo," Pavia, Italy.

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..
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http://dx.doi.org/10.1055/s-0040-1714346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645815PMC
September 2020

Overview of the rarest causes of fever in newborns: handy hints for the neonatologist.

J Perinatol 2021 Mar 27;41(3):372-382. Epub 2020 Jul 27.

Department of Life Sciences and Public Health, Fondazione Policlinico Universitario "A. Gemelli" IRCCS, Rome, Italy.

Neonatal causes of fever are a major source of concern for clinicians. If fever is combined with organ-specific sterile inflammatory manifestations the suspicion of autoinflammatory disorders should be considered, and the list of such conditions starting in the neonatal period includes chronic infantile neurological cutaneous articular syndrome, mevalonate kinase deficiency, deficiency of the interleukin-1 receptor antagonist, otulipenia, STING-associated vasculopathy with onset in infancy and Blau syndrome. Other causes of noninfectious fever that can rarely occur in newborns are Kawasaki disease, Behçet's disease, and hemophagocytic lymphohistiocytosis. Diagnosis of these exceptionally rare disorders is challenging for neonatologists. An early recognition of these complex diseases might lead to use more specific or rational drugs preventing permanent consequences. This review focuses on the rarest causes of fever occurring in the neonatal age with the aim of portraying many protean clinical pictures associated with fever and reviewing the potential available treatments.
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http://dx.doi.org/10.1038/s41372-020-0744-8DOI Listing
March 2021

Age and morphology of posterior communicating artery aneurysms.

Sci Rep 2020 07 14;10(1):11545. Epub 2020 Jul 14.

Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.

Risk of intracranial aneurysm rupture could be affected by geometric features of intracranial aneurysms and the surrounding vasculature in a location specific manner. Our goal is to investigate the morphological characteristics associated with ruptured posterior communicating artery (PCoA) aneurysms, as well as patient factors associated with the morphological parameters. Three-dimensional morphological parameters in 409 patients with 432 PCoA aneurysms diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016 who had available CT angiography (CTA) or digital subtraction angiography (DSA) were evaluated. Morphological parameters examined included aneurysm wall irregularity, presence of a daughter dome, presence of hypoplastic or aplastic A1 arteries and hypoplastic or fetal PCoA, perpendicular height, width, neck diameter, aspect and size ratio, height/width ratio, and diameters and angles of surrounding parent and daughter vessels. Univariable and multivariable statistical analyses were performed to determine the association of morphological parameters with rupture of PCoA aneurysms. Additional analyses were performed to determine the association of patient factors with the morphological parameters. Irregular, multilobed PCoA aneurysms with larger height/width ratios and larger flow angles were associated with ruptured PCoA aneurysms, whereas perpendicular height was inversely associated with rupture in a multivariable model. Older age was associated with lower aspect ratio, with a trend towards lower height/width ratio and smaller flow angle, features that are associated with a lower rupture risk. Morphological parameters are easy to assess and could help in risk stratification in patients with unruptured PCoA aneurysms. PCoA aneurysms diagnosed at older age have morphological features associated with lower risk.
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http://dx.doi.org/10.1038/s41598-020-68276-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360743PMC
July 2020

Multichannel Intraluminal Impedance and pH Monitoring: A Step Towards Pediatric Reference Values.

J Neurogastroenterol Motil 2020 07;26(3):370-377

Department of Pediatrics, Aldo Moro University of Bari - Giovanni XXIII Hospital, Bari, Italy.

Background/aims: Combined multichannel intraluminal impedance and pH monitoring (MII/pH) is considered the most accurate test to detect gastroesophageal reflux (GER), however lacking reference values. We aim to determine reference values for the pediatric population and to correlate these values with age and postprandial/fasting period.

Methods: We evaluated MII/pH traces from patients (newborns, infants, and children) admitted to 3 Italian hospitals and who underwent MII/ pH for suspected GER disease. Patients with MII/pH traces that showed significant symptom-reflux associations and/or a pathological reflux index (> 6% for newborns and infants, > 3% for children) were excluded. Traces were analysed in their entirety, and in the postprandial period (first hour after a meal) and the fasting period (the following hours before the next meal) separately.

Results: A total of 195 patients (46 newborns, 83 infants, and 66 children) were included. Age positively correlated with frequency of acidic GER events ( = 0.37, < 0.05) and negatively associated with weakly acidic GER events ( = 0.46, < 0.05).

Conclusions: This study describes the distribution of MII/pH values in a pediatric population with normally acidic GER exposure and no significant association between GER events and symptoms. These MII/pH values may be used as reference values in clinical practice for a corrected GER disease diagnosis in the pediatric population.
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http://dx.doi.org/10.5056/jnm19205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329155PMC
July 2020

Optic Neuropathy Due to Compression by an Ectatic Internal Carotid Artery Within the Orbital Apex.

J Neuroophthalmol 2021 03;41(1):e103-e104

Departments of Radiology (MTC, AAZ) and Neurosurgery (RD), Brigham and Women's Hospital, Boston, Massachusetts; and Department of Neurology (SP), Division of Neuro-Ophthalmology, Brigham and Women's Hospital, Boston, Massachusetts.

Abstract: Neurovascular compression is a rare but potentially treatable cause of optic neuropathy. Although incidental contact of the cisternal optic nerve and internal carotid artery (ICA) is common, compressive optic neuropathy occurring within the orbital apex has not been comprehensively described. We report a case of intra-orbital and intracanalicular optic nerve compression due to an ectatic ICA in a patient with congenital absence of the contralateral ICA. This report describes the complementary roles of advanced neuroimaging and neuro-ophthalmologic examination in rendering the diagnosis.
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http://dx.doi.org/10.1097/WNO.0000000000000975DOI Listing
March 2021

Novel Coronavirus disease (COVID-19) in newborns and infants: what we know so far.

Ital J Pediatr 2020 Apr 29;46(1):56. Epub 2020 Apr 29.

Neonatal Intensive Care Unit, Department of Neonatology, Bambino Gesù Children's Hospital, IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy.

Recently, an outbreak of viral pneumonitis in Wuhan, Hubei, China successively spread as a global pandemia, led to the identification of a novel betacoronavirus species, the 2019 novel coronavirus, successively designated 2019-nCoV then SARS-CoV-2). The SARS-CoV-2 causes a clinical syndrome designated coronavirus disease 2019 (COVID19) with a spectrum of manifestations ranging from mild upper respiratory tract infection to severe pneumonitis, acute respiratory distress syndrome (ARDS) and death. Few cases have been observed in children and adolescents who seem to have a more favorable clinical course than other age groups, and even fewer in newborn babies. This review provides an overview of the knowledge on SARS-CoV-2 epidemiology, transmission, the associated clinical presentation and outcomes in newborns and infants up to 6 months of life.
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http://dx.doi.org/10.1186/s13052-020-0820-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190200PMC
April 2020

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in twin sisters with two CD36 frameshift mutations.

Neurol Sci 2020 Aug 28;41(8):2271-2274. Epub 2020 Apr 28.

Institute of Pediatrics, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Rome, Italy.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical radiological syndrome with good prognosis that affects mainly children or young adults. We describe two cases of MERS, associated with echovirus 6 and influenza A infection, in two twin sisters, at the age of 4 years. Genetic analysis was performed; next exome sequencing was performed on twins to disclose the eventual causative gene. Two different frameshift mutations in the CD36 gene [NM_000072] were found in both twins and confirmed by Sanger sequencing. To best of our knowledge, we report an association between CD36 mutation and MERS. We think that this relation between CD36 and inflammation has had a crucial role in the same callosal alteration during viral disease in the twin sister with the same gene mutation.
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http://dx.doi.org/10.1007/s10072-020-04417-2DOI Listing
August 2020