Comparison Between Patent Ductus Arteriosus Stent and Modified Blalock-Taussig Shunt as Palliation for Infants With Ductal-Dependent Pulmonary Blood Flow: Insights From the Congenital Catheterization Research Collaborative.

BACKGROUND: Infants with ductal-dependent pulmonary blood flow may undergo palliation with either a patent ductus arteriosus (PDA) stent or a modified Blalock-Taussig (BT) shunt. A balanced multicenter comparison of these 2 approaches is lacking. METHODS: Infants with ductal-dependent pulmonary blood flow palliated with either a PDA stent or a BT shunt from January 2008 to November 2015 were reviewed from the 4 member centers of the Congenital Catheterization Research Collaborative. Outcomes were compared by use of propensity score adjustment to account for baseline differences between groups. RESULTS: One hundred six patients with a PDA stent and 251 patients with a BT shunt were included. The groups differed in underlying anatomy (expected 2-ventricle circulation in 60% of PDA stents versus 45% of BT shunts; P=0.001) and presence of antegrade pulmonary blood flow (61% of PDA stents versus 38% of BT shunts; P<0.001). After propensity score adjustment, there was no difference in the hazard of the primary composite outcome of death or unplanned reintervention to treat cyanosis (hazard ratio, 0.8; 95% confidence interval [CI], 0.52-1.23; P=0.31). Other reinterventions were more common in the PDA stent group (hazard ratio, 29.8; 95% CI, 9.8-91.1; P<0.001). However, the PDA stent group had a lower adjusted intensive care unit length of stay (5.3 days [95% CI, 4.2-6.7] versus 9.19 days [95% CI, 7.9-10.6]; P<0.001), a lower risk of diuretic use at discharge (odds ratio, 0.4; 95% CI, 0.25-0.64; P<0.001) and procedural complications (odds ratio, 0.4; 95% CI, 0.2-0.77; P=0.006), and larger (152 mm2/m2 [95% CI, 132-176] versus 125 mm2/m2 [95% CI, 113-138]; P=0.029) and more symmetrical (symmetry index, 0.84 [95% CI, 0.8-0.89] versus 0.77 [95% CI, 0.75-0.8]; P=0.008] pulmonary arteries at the time of subsequent surgical repair or last follow-up. CONCLUSIONS: In this multicenter comparison of palliative PDA stent and BT shunt for infants with ductal-dependent pulmonary blood flow adjusted for differences in patient factors, there was no difference in the primary end point, death or unplanned reintervention to treat cyanosis. However, other markers of morbidity and pulmonary artery size favored the PDA stent group, supporting PDA stent as a reasonable alternative to BT shunt in select patients.

Atrial Septal Defect Closure: Not Always Straightforward.

A nine-year old boy presented following a chest x-ray for COVID-19 infection that showed cardiomegaly. Transthoracic echocardiogram revealed a large atrial septal defect, dilated right heart, and normal function. Surgical repair was performed eight weeks after his COVID diagnosis. After weaning from cardiopulmonary bypass, pulmonary artery pressures were 2/3 systemic and ectopy was seen, requiring inotropes, nitric oxide, lidocaine, and amiodarone. He was discharged on postoperative day (POD) 5. On POD 6, he presented with acute right foot ischemia. Computed tomography showed a large aortic thrombus, requiring emergent thrombectomy. Coagulopathy workup was negative. Cardiac magnetic resonance imaging (CMR) and catheterization showed reduced biventricular function and diastolic dysfunction. Diuretics and ß blockers were started, with gradual improvement in left ventricular systolic function.

Regionalization or Access to Care? A Joint Pediatric Heart Care Program That Achieves Both: One Program-Two Sites.

Background: Regionalization of care for children with congenital heart disease has been proposed as a method to improve outcomes. This has raised concerns about limiting access to care. We present the details of a joint pediatric heart care program (JPHCP) which utilized regionalization and actually improved access to care. Methods: In 2017, Kentucky Children's Hospital (KCH) launched the JPHCP with Cincinnati Children's Hospital Medical Center (CCHMC). This unique satellite model was the product of several years of planning, leading to a comprehensive strategy with shared personnel, conferences, and a robust transfer system; "one program-two sites." Results: Between March 2017 and the end of June 2022, 355 operations were performed at KCH under the auspices of the JPHCP. As of the most recent published Society of Thoracic Surgeons (STS) outcome report (through the end of June 2021), for all STAT categories, the JPHCP at KCH outperformed the STS overall in postoperative length of stay, and the mortality rate was lower than expected for the case mix. Of the 355 operations, there were 131 STAT 1, 148 STAT 2, 40 STAT 3, and 36 STAT 4 operations, with two operative mortalities: an adult undergoing surgery for Ebstein anomaly, and a premature infant who died from severe lung disease many months after aortopexy. Conclusions: With a select case mix, and by affiliating with a large volume congenital heart center, the creation of the JPHCP at KCH was able to achieve excellent congenital heart surgery results. Importantly, access to care was improved for those children at the more remote location utilizing this one program-two sites model.

Brain tumors in owl monkeys inoculated with a human polyomavirus (JC virus).

Owl monkeys were inoculated intracerebrally, subcutaneously, and intravenously with JC, BK, or SV40 virus. Two of four adult owl monkeys inoculated with JC virus, a human polyomavirus, developed brain tumors at 16 and 25 months after inoculation, respectively. A grade 3 to grade 4 astrocytoma (resembling a human glioblastoma multiforme) was found in the left cerebral hemisphere and brainstem of one monkey. The second monkey developed a malignant tumor in the left cerebral hemisphere containing both glial and neuronal cell types. Impression smears prepared from unfixed tissue of this tumor showed cells that contained polyomavirus T antigen. Virion antigens were not detected. Tumor cells cultured in vitro also contained T antigen but were negative for virion antigen. Infectious virus was not isolated from extracts of this tumor.

Differences in Cost of Care by Palliation Strategy for Infants With Ductal-Dependent Pulmonary Blood Flow.

BACKGROUND: In infants with ductal-dependent pulmonary blood flow, initial palliation with patent ductus arteriosus (PDA) stent or modified Blalock-Taussig (BT) shunt have comparable mortality but discrepant length of stay, procedural complication rates and reintervention burdens, which may influence cost. The relative economic impact of these palliation strategies is unknown. METHODS AND RESULTS: Retrospective study of infants with ductal-dependent pulmonary blood flow palliated with PDA stent (n=104) or BT shunt (n=251) from 2008 to 2015 at 4 centers of the Congenital Catheterization Research Collaborative. Inflation-adjusted inpatient hospital costs were calculated for first year of life using Pediatric Health Information System data. Costs derived from outpatient catheterizations not in Pediatric Health Information System were imputed. Costs were compared using propensity score-adjusted multivariable models, to account for baseline differences between groups. After propensity score adjustment, first year of life costs were significantly lower in PDA stent ($215 825 [190 644-244 333]) than BT shunt ($249 855 [230 693-270 609]) patients ( P=0.05). After addition of imputed costs, first year of life costs were not significantly different between PDA stent ($226 403 [200 274-255 941]) and BT shunt ($252 072 [232 955-272 759]) groups ( P=0.15). Patient characteristics associated with higher costs included: younger gestational age, genetic syndrome, noncardiac diagnoses, procedural complications, extracorporeal membrane oxygenation, duration of ventilation, intensive care unit and hospital length of stay and reintervention ( P≤0.02 for all). CONCLUSIONS: In this first multicenter comparative cost study of PDA stent or BT shunt as palliation for infants with ductal-dependent pulmonary blood flow, adjusted for baseline differences, PDA stent was associated with lower to equivalent costs over the first year of life. Combined with previous evidence suggesting clinical noninferiority, these findings suggest that PDA stent provides competitive health care value.

Depression in lymphocyte response to general mitogens by owl monkeys infected with Herpesvirus saimiri.

The effect of Herpesvirus saimiri (HVS) infection on the response of owl monkey lymphocytes to general mitogens was examined during the development of neoplastic disease. The reactivity of the lymphocytes was then correlated with the clinical condition of the infected monkeys and the content of virus rescued from the peripheral blood lymphocytes (PBL). Eight monkeys developed lymphoma which, in six monkeys, was accompanied by lymphocytic leukemia. All animals that died of HVS-induced neoplasia consistently showed a lack of mitogenic response to phytohemagglutinin and concanavalin A. The response to pokeweed mitogen, while always reduced, was generally less markedly affected than the response to the other two mitogens. Lymphocytes from five of the leukemic animals demonstrated an elevated level of spontaneous DNA synthesis in culture late in the disease. This increased spontaneous DNA synthesis tended to correlate with the rescue of HVS from the PBL as demonstrated by the infective center assay. Although mitogenic hyporesponsiveness corresponded with HVS rescue from PBL in six of nine monkeys, the impairment of normal lymphocyte responsiveness sometimes preceded virus recovery.

Infection of capuchin monkeys (Cebus albifrons) with Herpesvirus saimiri.

Herpesvirus saimiri (HVS) induced persistent, clinically inapparent infections of long-term duration in capuchin monkeys (Cebus albifrons). The infections were characterized by development of antibody to HVS-associated antigens and recovery of low levels of virus-genome-carrying lymphocytes in the peripheral blood. Peripheral lymphocyte counts remained in low-normal to normal ranges and no physical signs of lymphoma were evident. Prednisolone treatment caused immunosuppression in one monkey; this was accompanied by a progressive loss of humoral antibody to HVS-associated antigens, but neoplastic disease did not develop.

Cerebrospinal fluid markers in African Burkitt's lymphoma with central nervous system involvement.

Several cerebrospinal fluid markers were found to be elevated in Burkitt's lymphoma patients with central nervous system (CNS) involvement. Antibody levels to the virus capsid antigen of the Epstein-Barr virus and to the brain cell antigens myelin and cerebroside were elevated during active CNS disease. Immune complexes were present in levels above 100 micrograms/ml in most patients with CNS involvement but tended to be low or negative in patients without CNS disease. Oligoclonal IgG bands were present in 12 of 13 patients with CNS disease and in only 3 of 26 patients with no clinical evidence of disease. None of these markers were present in 6 other tumor patients without CNS disease. The presence of these markers in 12 of 13 patients in whom CNS disease was involved suggests that these markers may be useful in determining the status of the tumor with regard to involvement of the CNS.

Spontaneous lymphoma associated with Herpesvirus saimiri in owl monkeys.

Two cases of lymphoma and one case of lymphoproliferative disease were found in a group of 7 owl monkeys imported into our colony as a single group. Herpesvirus saimiri (HVS) was isolated from the tumor cells of 1 lymphoma by cocultivation and from kidney cell cultures from the monkey with lymphoproliferative disease. Antibody to HVS was found in serum samples from 2 monkeys positive for HVS but not in the sera from the 4 clinically normal monkeys. Antibody to Epstein-Barr virus-infected cells was also found in the serum from the animal with lymphoma.

Pilot studies with human interferon in Herpesvirus saimiri-induced lymphoma in owl monkeys.

The nature of Herpesvirus saimiri-induced disease in owl monkeys is described with emphasis on those biological parameters useful in monitoring the disease. These parameters are lymphocyte response to general mitogens, lymphocyte-infective centers, and antibody to virus-associated early antigen. Human interferon was used in treating owl monkeys with virus-induced leukemia. In 2 animals evidence was obtained that suggested a positive antileukemic effect.

Sex differences in response to dietary manipulation in rats with hypertension and myocardial hypertrophy.

Studies of the effect of sex on the metabolic state of rats with chronic hypertension and concomitant myocardial hypertrophy were conducted. Female and male spontaneously hypertensive rats (SHRs) with early myocardial hypertrophy (5.5 mo old) were used. Serum fatty acids, liver glycogen, and myocardial glycogen were measured at baseline and after the rats were deprived of food for 24 h. The metabolic effects of progressive myocardial hypertrophy in females were assessed in additional groups of female SHRs (5.5 or 12 mo old) under the following conditions: control, food deprived, or food deprived and refed with equienergetic lipid-rich (38.9% of total energy) or carbohydrate-rich (76.5% of total energy) diets. Despite no differences in serum fatty acids, females had significantly higher baseline myocardial glycogen and liver glycogen concentrations than males. In response to food deprivation, females continued to have significantly higher myocardial glycogen and fatty acid concentrations than males, whereas there were no sex differences in liver glycogen, which was depleted in both males and females. Older hypertensive females had higher baseline fatty acid concentrations and lower liver glycogen concentrations than younger females, whereas there were no differences in myocardial glycogen. Food deprivation doubled fatty acid concentrations, depleted liver glycogen, and increased myocardial glycogen in both age groups. In both age groups, fatty acid concentrations and liver glycogen did not return to baseline values after food deprivation and refeeding. In both age groups, fatty acid concentrations increased further after the lipid-rich diet whereas liver glycogen concentrations returned to approximately 50% of baseline values after the carbohydrate-rich diet. Refeeding with either diet did not significantly increase myocardial glycogen further. Thus, the metabolic response to dietary manipulation was influenced by both sex and, in females, progressive pathology.

Oligoclonal IgG in CSF of patients with African Burkitt's lymphoma.

Oligoclonal IgG bands were detected in CSF from 12 of 13 patients with African Burkitt's lymphoma (BL) who exhibited neurologic signs or symptoms of CNS involvement. Twenty-three of 26 patients free of neurologic involvement with this tumor were found to lack the oligoclonal IgG bands in their CSF. None of six patients with non-BL included in this study had these bands in their CSF. None of six patients with non-BL included in this study had these bands in their CSF samples. These findings suggest that detection of these bands may be a useful adjunct for determining the presence of African BL that invades the CNS.

Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls.

Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.

Measles and canine distemper antibody. Presence in sera from patients with multiple sclerosis and matched control subjects.

Antibody to measles virus and canine distemper virus (CDV) was demonstrated in sera from patients with multiple sclerosis (MS) and from carefully matched control subjects. Elevated measles and CDV antibody titers were found in patients with MS when compared with the matched control subjects. The correlation between the measles and CDV antibody titers was quite high, suggesting that the antibody levels between the two viruses are very closely related. Based on the results of our study and a review of the literature, our conclusion is that the CDV antibody levels in patients with MS and matched control subjects are associated with occurrence of measles virus antibodies.

Micromethod for detection of oligoclonal IgG in unconcentrated CSF by polyacrylamide gel electrophoresis.

A micromethod to detect oligoclonal IgG from 50 microL of unconcentrated CSF was developed by using polyacrylamide gel electrophoresis in sodium dodecyl sulfate (SDS-PAGE). Of 17 patients with multiple sclerosis, oligoclonal bands were demonstrated in 16 instances (94%) by micro-SDS-PAGE and in 13 (76%) by agarose gel electrophoresis. The corresponding figures among 30 patients with optic neuritis were 16 (54%) and five (17%), respectively, and among ten patients with other neurological disease the figures were two (20%) and none, respectively. Thus, micro-SDS-PAGE is more sensitive than agarose gel electrophoresis for detection of oligoclonal IgG. The small volume of unconcentrated CSF that is required enhances the usefulness of this test.

Suppressor cell activity in multiple sclerosis.

Patients with multiple sclerosis and matched controls were tested for lymphocyte stimulation response and induction of suppressor cell activity in response to concanavalin A (Con A) and antigens from axolemma or myelin. Of 17 stable patients, 6 failed to have a suppressor cell response activated by one of these brain cell antigens. Among the patients who lacked these suppressor responses, five had lymphocyte stimulation responses to the same antigens. All matched controls except for one had suppressor cell responses to these antigens and none responded with a positive cellular immune reaction. We found no difference in lymphoproliferative responses to Con A in patients and controls. The level of suppressor cell activity induced by Con A in the stable MS patients varied but did not differ significantly from that of controls.

Viral antibodies in twins with multiple sclerosis.

Viral antibodies to measles, rubella, corona, vaccinia, and mumps viruses in serum and CSF (and to Epstein-Barr virus in serum only) were studied in 24 twin pairs, both discordant and concordant for clinical MS. In pairs, CSF antibody titers for rubella in MS monozygotic and dizygotic twins and for vaccinia in dizygotic twins were higher than for unaffected twins. Increased CSF titers among MS twins existed for measles, rubella, and vaccinia when pairing was ignored. Among MS twins, serum rubella and measles and CSF measles antibody titers, and CSF:serum ratios for measles virus, were higher in those who were DW2 positive.

Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease?

OBJECTIVE: The outcome of children with cyanosis after cardiac surgical procedures is inferior to that of children who are acyanotic. Animal studies indicated detrimental effects of chronic hypoxia on myocardial metabolism and function. We studied whether the presence or the degree of cyanosis adversely affected myocardial adenosine triphosphate, ventricular function, and clinical outcome in children. METHODS: Forty-eight children who underwent repair of tetralogy of Fallot were divided according to their preoperative saturation: group I, 90% to 100% (n = 14 patients); group II, 80% to 89% (n = 16 patients); and group III, 65% to 79% (n = 18 patients). Adenosine triphosphate was measured from right ventricular biopsy specimens taken before ischemia, at 15 minutes of ischemia, at end-ischemia, and at 15 minutes of reperfusion. Ejection fraction was measured by echocardiography. RESULTS: Even before surgical ischemia, compared with groups I and II, group III had lower preoperative ejection fraction (59% +/- 2.9% vs 67% +/- 1.7% and 68% +/- 1.0%; P <.01) and lower preischemic adenosine triphosphate levels (15.1 +/- 2.1 vs 19.1 +/- 1.9 and 21.4 +/- 1.5 micromol/g dry weight; P <.01). After 15 minutes of ischemia, group III had lower adenosine triphosphate levels (11.2 +/- 1.8 vs 14.77 +/- 2.3 and 17. 6 +/- 3.1 micromol/g dry weight; P <.01). With reperfusion, both cyanotic groups lost further adenosine triphosphate compared with partial recovery in the acyanotic group (-22% +/- 3.8%, -20% +/- 3. 1% vs +18% +/- 1.8%; P <.01). Children in group III had a more complicated postoperative course as evidenced by longer ventilatory support (85 +/- 25 hours vs 31 +/- 15 and 40 +/- 21 hours; P =.07), inotropic support (86 +/- 23 hours vs 38 +/- 12 and 36 +/- 4 hours; P <.01), and intensive care unit stay (160 +/- 35 hours vs 60 +/- 10 and 82 +/- 18 hours; P =.02). CONCLUSIONS: The degree of cyanosis adversely affects myocardial adenosine triphosphate, function, and clinical outcome of children who undergo cardiac operation. Children with cyanosis should be identified as a higher risk group that could be targeted for supportive interventions.

Extracellular calcium concentration affects susceptibility to global ischemic injury in newborn but not adult hearts.

BACKGROUND: Whether immaturity in calcium handling, that persists for a time after birth, could increase sensitivity to extracellular calcium and affect the development of global ischemic injury in the newborn heart is unknown. To address this, the impact of alterations in extracellular calcium concentration on newborn vs. adult development of myocardial injury due to ischemia was studied. METHODS: In Study 1, hearts of 3-day-old piglets and adult pigs were perfused with 1 of 3 different calcium concentrations: control (0.13 mmol/L); intermediate (2.23 mmol/L); high (4.44 mmol/L) before normothermic ischemia. In Study 2, newborn hearts were allocated to perfusion with or without the L-calcium channel antagonist verapamil before high (4.44 mmol/L) calcium exposure, followed by normothermic ischemia. Tolerance to ischemia was assessed by determining the time to irreversible injury in all hearts, and maximal intraventricular pressures at peak injury. RESULTS: In adults, altering calcium did not significantly affect tolerance to ischemia. In newborns, increasing calcium exposure resulted in significantly greater intraventricular pressures at maximal injury when compared with the control (low) calcium group (p<.05). As well, newborns exposed to high calcium had a significantly shorter time to the development of ischemic injury compared with the other groups (p<.05). Those newborn hearts pretreated with an L-calcium channel antagonist before the high calcium exposure did not exhibit this increased susceptibility to ischemic injury (p<.05). CONCLUSIONS: In contrast to adults, the development of ischemic injury in the newborn heart is affected by changes in extracellular calcium, that can be modified with an L-calcium channel antagonist. This information could be used to prolong the safe preservation time of newborn donor hearts harvested for transplantation, as well as to minimize postoperative ventricular dysfunction.

Management of genital herpes simplex virus infection during pregnancy.

The clinical course and outcome of 58 pregnancies in 57 women with culture-verified genital herpes simplex virus (HSV) infection during gestation are reported. In 19 cases (33%) an active genital HSV infection was present within 1 week of delivery. Of the 60 infants delivered, 58 survived. No maternal or perinatal morbidity or mortality was attributable to HSV. This experience suggests that weekly culturing of the cervix and all other previously infected genital sites from the 36th week of gestation until delivery is an acceptable plan for managing such pregnancies. Women without evidence of infection at the onset of labor can be allowed to deliver vaginally. With appropriate precautions, breast-feeding by mothers with genital HSV infections is not contraindicated.