Hyperglycemia and Cytopenias as Signs of SARS-CoV-2 Delta Variant Infection in Preterm Infants.

Information regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in premature infants remains limited. Early in the pandemic, several studies reported that the risk of infection in infants was relatively small and that affected infants had a milder disease than what was seen in adults. Since the increase of the delta variant (SARS-CoV-2 B.1.617.2) within the population, there have been increased reports of more severe disease in infants. We present 3 cases of premature, very low birth weight infants with confirmed SARS-CoV-2 infection who presented with significant hyperglycemia and bone marrow dysfunction. Two infants had presumed vertical transmission, and 1 infant was infected by respiratory transmission. Despite the mode of transmission, symptom onset and duration were similar in all infants. All resolved with symptomatic management. In the context of the continuing pandemic, evaluation for SARS-CoV-2 infection should be considered in premature very low birth weight infants who demonstrate certain patterns of acute metabolic and hematologic abnormalities.

Balloon Valvuloplasty for Congenital Aortic Stenosis: Experience at a Tertiary Center in a Developing Country.

BACKGROUND: Aortic valve stenosis accounts for 3-6% of congenital heart disease. Balloon aortic valvuloplasty (BAV) is the preferred therapeutic intervention in many centers. However, most of the reported data are from developed countries. MATERIALS AND METHODS: We performed a retrospective single-center study involving consecutive eligible neonates and infants with congenital aortic stenosis admitted for percutaneous BAV between January 2005 and January 2016 to our tertiary center. We evaluated the short- and mid-term outcomes associated with the use of BAV as a treatment for congenital aortic stenosis (CAS) at a tertiary center in a developing country. Similarly, we compared these outcomes to those reported in developed countries. RESULTS: During the study period, a total of thirty patients, newborns (n = 15) and infants/children (n = 15), underwent BAV. Left ventricular systolic dysfunction was present in 56% of the patients. Isolated AS was present in 19 patients (63%). Associated anomalies were present in 11 patients (37%): seven (21%) had coarctation of the aorta, two (6%) had restrictive ventricular septal defects, one had mild Ebstein anomaly, one had Shone's syndrome, and one had cleft mitral valve. BAV was not associated with perioperative or immediate postoperative mortality. Immediately following the valvuloplasty, a more than mild aortic regurgitation was noted only in two patients (7%). A none-to-mild aortic regurgitation was noted in the remaining 93%. One patient died three months after the procedure. At a mean follow-up of 7 years, twenty patients (69%) had more than mild aortic regurgitation, and four patients (13%) required surgical intervention. Kaplan-Meier freedom from aortic valve reintervention was 97% at 1 year and 87% at 10 years of follow-up. CONCLUSION: Based on outcomes encountered at a tertiary center in a developing country, BAV is an effective and safe modality associated with low complication rates comparable to those reported in developed countries.

The first Fetal Echocardiography experience for Prenatal diagnosis of Congenital Heart Disease in Lebanon: Successes and challenges.

OBJECTIVES: To describe the first Lebanese fetal echocardiography experience for prenatal diagnosis of congenital heart diseases (CHD), showcase successes, and hurdles. METHODS: This was a retrospective study from January 2014 to December 2017. A total of 350 fetal echocardiograms for 299 fetuses were performed at the Children's Heart Center at the American University of Beirut, the only fetal center in Lebanon. Data were collected regarding diagnosis, reasons for referral, and timing of referral. RESULTS: The mean gestational age at presentation was 25.3 weeks (standard deviation 4.9 weeks). The primary reasons for referral were abnormal anomaly scan (81 27%), history of previous child with CHD (48 16%), and pre-existing maternal congenital heart disease (15 5%). A total of 144 fetal echocardiograms were normal and 155 patients were diagnosed prenatally with CHD giving a detection rate of 44%. The most identified cardiac lesions were ventricular septal defects (31, 20%), atrial septal defects (15, 9.7%). Significant CHD defined as major abnormalities which would impact pregnancy and future quality of life of the baby were identified in 78 fetuses, with a detection rate of 22%. CONCLUSION: High rates of detection are mainly due to low rates of referral when indicated and possibly parental anxiety regarding CHD diagnosis.

Knock-in mouse model of alternating hemiplegia of childhood: behavioral and electrophysiologic characterization.

OBJECTIVES: Mutations in the ATP1α3 subunit of the neuronal Na+/K+-ATPase are thought to be responsible for seizures, hemiplegias, and other symptoms of alternating hemiplegia of childhood (AHC). However, the mechanisms through which ATP1A3 mutations mediate their pathophysiologic consequences are not yet understood. The following hypotheses were investigated: (1) Our novel knock-in mouse carrying the most common heterozygous mutation causing AHC (D801N) will exhibit the manifestations of the human condition and display predisposition to seizures; and (2) the underlying pathophysiology in this mouse model involves increased excitability in response to electrical stimulation of Schaffer collaterals and abnormal predisposition to spreading depression (SD). METHODS: We generated the D801N mutant mouse (Mashlool, Mashl+/-) and compared mutant and wild-type (WT) littermates. Behavioral tests, amygdala kindling, flurothyl-induced seizure threshold, spontaneous recurrent seizures (SRS), and other paroxysmal activities were compared between groups. In vitro electrophysiologic slice experiments on hippocampus were performed to assess predisposition to hyperexcitability and SD. RESULTS: Mutant mice manifested a distinctive phenotype similar to that of humans with AHC. They had abnormal impulsivity, memory, gait, motor coordination, tremor, motor control, endogenous nociceptive response, paroxysmal hemiplegias, diplegias, dystonias, and SRS, as well as predisposition to kindling, to flurothyl-induced seizures, and to sudden unexpected death. Hippocampal slices of mutants, in contrast to WT animals, showed hyperexcitable responses to 1 Hz pulse-trains of electrical stimuli delivered to the Schaffer collaterals and had significantly longer duration of K+-induced SD responses. SIGNIFICANCE: Our model reproduces the major characteristics of human AHC, and indicates that ATP1α3 dysfunction results in abnormal short-term plasticity with increased excitability (potential mechanism for seizures) and a predisposition to more severe SD responses (potential mechanism for hemiplegias). This model of the human condition should help in understanding the molecular pathways underlying these phenotypes and may lead to identification of novel therapeutic strategies of ATP1α3 related disorders and seizures.