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Biomedical subjects

J B Atkinson

Publications and source records attributed to J B Atkinson.

At least 37 records · Page 2Linked to original sources

Favorable biology and outcome of stage IV-S neuroblastoma with supportive care or minimal therapy: a Children's Cancer Group study.

PURPOSE: Stage IV-S neuroblastoma is a metastatic disease associated with spontaneous regression and good survival, but 10% to 20% of infants die from early complications. The purpose of this study was to evaluate outcome and prognostic factors in infants with stage IV-S neuroblastoma treated prospectively with supportive care only or, in symptomatic patients, with low-dose cytotoxic therapy. PATIENTS AND METHODS: Eighty eligible infants were studied for response and survival with supportive care or, for symptomatic patients, cyclophosphamide 5 mg/kg/d for 5 days with or without hepatic radiation of 4.5 Gy over 3 days. Staging was reviewed centrally, and MYCN gene copy number, Shimada histopathologic classification, serum ferritin levels, and bone marrow immunocytology were determined. RESULTS: Stage IV-S and International Neuroblastoma Staging System stage 4S were 98% concordant. MYCN was not amplified in any of the tumors tested (n = 58), and Shimada histopathologic classification was favorable in 96% (n = 68/71). The 5-year event-free survival (EFS) rate for all infants was 86% and the survival rate was 92%. Supportive care was the only treatment provided for 44 (55%) of 80 infants, and their 5-year survival rate was 100%, compared with 81% survival for those requiring cytotoxic therapy for symptoms (P =.005). Five of six deaths were in infants younger than 2 months of age at diagnosis and were due to complications of extensive abdominal involvement with respiratory compromise or disseminated intravascular coagulation. Although age </= 3 months at diagnosis was significant for EFS (P =. 043), it was less significant for survival (P =.077). The only other significant factor predictive for improved survival was favorable Shimada histopathologic classification. Sites of metastatic involvement (liver, skin, or bone marrow) and surgical resection of the primary tumor were not significant for survival. CONCLUSION: This study confirms the favorable biologic features and excellent survival of infants with stage IV-S neuroblastoma with minimal therapy. Infants younger than 2 months old at diagnosis with rapidly progressive abdominal disease may benefit from earlier and more intensive treatment.

Adrenal Gland Neoplasms↗

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Adolescent↗

Prolongation of primate cardiac allograft survival by treatment with ANTI-CD40 ligand (CD154) antibody.

BACKGROUND: We evaluated whether a humanized anti-CD154 antibody (hu5c8) prolongs primate cardiac allograft survival. METHODS: Heterotopic cardiac allografts were performed between MHC class II-mismatched cynomolgus monkeys. Survival was compared between groups treated with a perioperative dosing of hu5c8 (group 1; n=6), sustained dosing with hu5c8 (group 2; n=3), and control regimens (n=4). All recipients received fresh donor-specific transfusions during surgery. RESULTS: Median graft survival was 49 days (range 14 to 56) in group 1 and 106 days (range 56 to 245) in group 2, compared with 5 days (range 5 to 6) for controls (P<0.05 for all comparisons). Lymphocytic infiltrates were often present in hu5c8-treated grafts with stable contractility. Donor-specific mixed lymphocyte reaction was generally preserved. Vasculitis and cellular intimal proliferation were prevalent in rejected grafts but occurred later and were less prevalent in group 2. CONCLUSIONS: Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.

Animals↗

Longitudinal analysis of fibroblast growth factor expression after transplantation and association with severity of cardiac allograft vasculopathy.

BACKGROUND: Vascular smooth muscle cell growth factors are postulated to contribute to cardiac allograft vasculopathy (CAV). Few data quantitatively address the timing, location, or stimuli for growth factor expression and relationship to CAV. METHODS AND RESULTS: Acidic fibroblast growth factor (aFGF) mRNA expression was determined in serial endomyocardial biopsies during the first year after transplantation. Patients with high levels of aFGF mRNA and elevations after the early posttransplant period had significantly more severe CAV than patients with low aFGF and no late elevations. CONCLUSIONS: Parenchymal aFGF expression varies between patients and in the same patient over time and correlates with development of CAV.

Biopsy↗

Current aspects of biology, risk assessment, and treatment of neuroblastoma.

Neuroblastoma is one of the most intensely studied solid malignancies that affect the pediatric age groups; its clinical presentation, treatment strategies and ultimate prognosis vary greatly. The biologic and genetic character of each tumor has an important impact on disease behavior, and clinical staging now incorporates these factors to generate an overall therapy plan. The clinical presentation of neuroblastoma is related to primary tumor location, production of metabolically active substances, and the presence of metastatic disease. There are also prognostically important associated syndromes including opsoclonus-myoclonus, Horner's syndrome, neurofibromatosis, and a variety of other neurocristopathies. The histologic features of the tumor are of prognostic significance and are utilized in treatment stratification. The International Neuroblastoma Staging System (INSS) has unified classic clinical staging. Features at diagnosis and those determined by initial operation are combined with biologic prognostic factors to achieve risk group assignment for virtually all patients. There are groups of children in which limited therapy is curative and intermediate-risk situations where standard multimodality treatment provides favorable outcomes. Unfortunately, there are many patients with high-risk disease that require intensive strategies, but success is still limited. It is in these most resistant patients that innovative approaches are being undertaken and novel strategies are being investigated.

Adolescent↗

The influence of gestational age and mode of delivery on infants with gastroschisis.

BACKGROUND/PURPOSE: It has been proposed that preterm and prelabor cesarean section may improve the outcome of infants with gastroschisis. The purpose of this study is to examine the impact of gestation and delivery method on infants with gastroschisis. METHODS: The medical records of 60 infants with gastroschisis treated at a tertiary care center from 1985 through 1995 were reviewed retrospectively. The gestational age, the mode of delivery, the type of operative repair, and the length of hospital stay were recorded for each patient. RESULTS: Infants born vaginally were more likely to require silo stage repair than those delivered by cesarean section (21 of 29 v. 11 of 31, P<.01). Infants born vaginally also had longer hospital stay than those delivered by cesarean section (53 v. 39 days, P = .19). Infants born before 33 weeks' of gestation stayed longer in the hospital than those born after 33 weeks. After 33 weeks' gestation, infants had similar hospital stay regardless of the gestational age. CONCLUSIONS: Cesarean section delivery was beneficial for infants with gastroschisis. Preterm delivery did not shorten the length of hospital stay. The role of elective cesarean section delivery at term should be considered for infants with gastroschisis diagnosed antenatally.

Cesarean Section↗

Antireflux surgery in children under 3 months of age.

PURPOSE: The aim of this study was to analyze the indications and results of fundoplication in 110 infants under 3 months of age. METHODS: A retrospective review was conducted on the charts of all infants operated on for gastroesophageal reflux disease (GERD) at the UCLA Medical Center from January 1980 to December 1997. There were 59 boys and 51 girls. Recurrent emesis was the indication for operation in 62 of 110 infants, and respiratory symptoms in 85 of 110, with 54 of 110 having both. Neurological impairment was present in 32%. Prematurity was present in 21%; 35% had associated anomalies. Overall, 81 of 110 infants (73.6%) had one or more associated major malformations or disorders. Reflux was confirmed by upper gastrointestinal series findings in 63 of 78, esophageal pH monitoring in 60 of 62, and endoscopy in five of seven. RESULTS: Mean age at operation was 1.8+/-0.1 months and mean weight was 3,686+/-90.2 g. A Nissen fundoplication was performed on 104 children, and six underwent a Thal procedure. Thirty-one had a gastric emptying procedure for delayed gastric emptying. Complications occurred in 7 infants. Emesis was controlled in 57 of 62 patients, aspiration in 38 of 48, and apneic spells in 54 of 57. Follow-up greater than 6 months was available for 73 patients. There were nine late deaths, all related to severe associated malformations. Seven patients required a redo fundoplication for recurrent reflux. CONCLUSIONS: Nissen fundoplication can be performed safely in symptomatic infants under 3 months of age with low mortality and morbidity rates and with resolution of the presenting symptoms in 79% of infants.

Female↗

Effects of intraabdominally insufflated carbon dioxide and elevated intraabdominal pressure on postoperative gastrointestinal transit: an experimental study in mice.

BACKGROUND/PURPOSE: Postoperative ileus after abdominal operations is thought to be related to the degree of surgical trauma, and it has been shown that the simple act of opening the peritoneum can decrease gastrointestinal motility. Accordingly, some investigators have shown a reduction in the duration of postoperative ileus after laparoscopic procedures. It is not clear, however, if this reduction is secondary to less manipulation of the viscera or to the lack of an abdominal incision. The aim of this study was to determine the effect of intraabdominal insufflation with CO2 on postoperative gastrointestinal transit. METHODS: Twenty-eight male mice weighing between 25 and 30 g were divided randomly into 4 groups: Control (unoperated), Incision (conventional laparotomy), Cecal (laparotomy plus cecal manipulation), and Insufflation (abdominal insufflation with CO2). Postoperative gastrointestinal motility was assessed by weighing total fecal output over the first 15 postoperative hours. RESULTS: Fecal pellet output over 15 hours in the untreated control group was 1.20 +/- 0.12 g. In mice subjected to peritoneal incision alone, fecal pellet output was significantly decreased to 0.82 +/- 0.11 g (P < .05). However, in mice subjected to abdominal insufflation with CO2, fecal pellet output was not significantly different from untreated controls (1.2 +/- 0.05 g; not significant). Fecal pellet output was markedly reduced by incision combined with cecal manipulation (0.24 +/- 0.02 g, P < .01). CONCLUSIONS: The current study findings show that abdominal insufflation, in a procedure similar to that used during laparoscopic surgery, had no measurable effect on gastrointestinal transit in awake mice. This suggests that the lack of an abdominal incision can contribute to a reduced postoperative ileus after abdominal surgery.

Abdomen↗

Gastric emptying procedures decrease the risk of postoperative recurrent reflux in children with delayed gastric emptying.

PURPOSE: Although several centers often perform gastric emptying procedures (GEP) together with fundoplication for gastroesophageal reflux (GER) and delayed gastric emptying (DGE), the benefit of GEP is controversial. The present study addresses the question of whether adding a GEP in children with preoperatively diagnosed GER and DGE affects the recurrence rate of GER after Nissen fundoplication (NF). METHODS: A retrospective chart review was performed on all children under the age of 16 years, operated on for GER from 1980 to 1997, who had a preoperative diagnosis of DGE, and at least 6 months of follow-up. Gastric retention of more than 50% of a radiolabeled meal at 90 minutes was considered DGE. Recurrent reflux was defined as reappearance of GER symptoms, confirmed by postoperative esophagram or 24 hours of pH monitoring. RESULTS: Of the 183 patients with DGE, 92 were available for long-term follow-up. Of these, 20 had no gastric emptying procedure performed (no-GEP group) and 72 had a GEP performed together with an NF (GEP group). Groups were comparable as to age at operation, mean follow-up time, male to female ratio and prevalence of associated anomalies. A higher prevalence of neurological impairment (NI) was present in the GEP group (48.6% v20.0%). Mean preoperative gastric retention was significantly higher in the GEP group (69.9 +/- 1.3%) than in the no-GEP group (61.4 +/- 2.2%). No complications resulted from the GEP. Recurrent reflux rate was 18.1% in the GEP group (13 of 72) versus 35.0% (7 of 20) in the no-GEP group. Actuarial analysis disclosed a marginally significant difference in the rate of recurrent reflux between the groups (P = .057) and estimation of the relative risk showed a 1.94 increase of recurrent reflux risk in the no-GEP (0.89<RR<4.20). CONCLUSIONS: Children with DGE, who did not have GEP, had twice the frequency of recurrent reflux as those who had a GER Preoperative screening for DGE, as well as operative correction of DGE at the time of fundoplication, is therefore recommended.

Child, Preschool↗

Reoperation after esophageal replacement in childhood.

BACKGROUND: Esophageal replacement is associated with significant morbidity that may lead to operative interventions. This study reviews the management and outcome of children who underwent reoperation after esophageal replacement. METHODS: Eighteen patients who underwent esophageal replacement from 1985 to 1997 were reviewed retrospectively. Ten patients underwent reoperation. Patient management, perioperative morbidity, and the dietary intake at follow-up were recorded for each patient. RESULTS: Of the reoperated patients, 7 had esophageal atresia, 2 had caustic ingestion, and 1 had achalasia. Nine patients received a colon interposition, and 1 received a reverse gastric tube as the initial esophageal replacement. Seven patients required revision of the anastomoses. Three patients required complex esophageal reconstruction: 1 underwent gastric transposition, 1 underwent free jejunal graft, and 1 underwent gastric transposition combined with free jejunal graft. Seven patients were eating well at follow-up. Two patients still required partial gastrostomy tube feeding. One patient died 6 months postoperatively from aspiration pneumonia. CONCLUSIONS: Esophageal replacement continues to be a challenging operation associated with significant complications. Most reoperative procedures were directed toward strictures and persistent fistulae. Complete graft failure can be managed by gastric transposition or free jejunal graft. Despite the perioperative morbidity, most patients have good functional outcome.

Adolescent↗

Inflammatory myofibroblastic tumour of the breast: report of a case with giant vacuolated cells.

Inflammatory myofibroblastic tumours (IMTs) or inflammatory pseudo-tumours are uncommon lesions of unknown aetiology. The majority of the cases are reported in the lungs of young patients. Extra-pulmonary anatomic locations include the abdomen and pelvis, but rare cases have been described in the breast. We describe an IMT in an 86-year-old female, presenting as a well-circumscribed palpable mass in the left breast. Histologically the remarkable feature was the presence of giant vacuolated cells intermixed with spindle cells and a prominent plasma cell infiltrate immersed in a fibrous hyalinized stroma. Immunohistochemical and electron microscopy studies demonstrated the myofibroblastic nature of the giant vacuolated cells and the spindle cells, and the polyclonal nature of the plasma cells. The morphologic and immunohistochemical findings supported the diagnosis of IMT. The biological behaviour of IMT in this age group is unknown and surgical excision with close mammographic follow-up is considered to be appropriate treatment for this lesion in the breast.

Journal Article↗

Pigmented schwannoma of the ventral spinal cord.

Pigmented schwannomas of the spinal canal are rare entities. We present a case of such in an unusual, ventral intradural, extramedullary location in a 27-year-old man. Imaging and histopathologic findings, including electron microscopy, showed an intradural, extramedullary pigmented schwannoma, densely adherent to the leptomeninges of the anterior median septum. This lesion is demonstrative of the neuroectodermal origin of these lesions and represents a rare location of these tumors.

Adult↗

Simplifying the Waterston's stratification of infants with tracheoesophageal fistula.

The survival of infants with tracheoesophageal fistula was stratified by David J. Waterston et al. in 1962. This classification has been used as a guide to direct the timing of operative intervention in these infants. This study examines the current applicability of this classification system. The hospital records of 64 infants with esophageal atresia and/or tracheoesophageal fistula were reviewed. The survival rate was analyzed as a function of the infants' risk stratification, birth weight, and additional anomalies. Twenty-three infants were in Waterston Group A, 20 infants in Group B, and 21 infants in Group C. The survival of all infants was 81 per cent. Six infants died after recognition of severe anomalies and withdrawal of care, four infants died of cardiopulmonary arrest, and two infants died of sepsis. The survival of infants in both Groups A and B was 100 per cent, in contrast to 43 per cent survival in Group C. Only infants who weighed <1800 g or had severe additional anomalies were at risk of dying. Therefore, the classification of infants with esophageal atresia and/or tracheoesophageal fistula may be simplified by combining Waterston's Groups A and B into a single risk stratum.

Esophageal Atresia↗

Occult breast carcinoma presenting as an axillary mass.

Breast carcinoma presents rarely (<5% of cases) as an axillary mass without an obvious primary tumor. The value of mammography in detecting an occult breast carcinoma is low, with a sensitivity of 29 per cent and specificity of 73 per cent. MRI and positron emission tomography (PET) are potentially more sensitive in this setting. We present a case recently seen at the Vanderbilt University Hospital, a 63-year-old woman with a 2-cm painless mass in the right axilla. Mammography was negative, and fine needle aspiration revealed atypical cells suspicious for malignancy. An excisional biopsy of the right axillary lymph node revealed metastatic adenocarcinoma, most likely breast primary. A PET showed increased uptake of 18-fluorodeoxyglucose and 99m Technetium in the right axilla and the right lateral breast. The patient underwent right modified radical mastectomy. The final pathological report revealed a 0.9-cm primary tumor in the upper inner quadrant of the breast and 1 of 41 nodes positive for tumor. This case confirms that mammography has low sensitivity in identifying the primary tumor in occult breast carcinoma and illustrates the usefulness of PET in identifying the primary tumor. We advocate an aggressive approach to evaluation of the breast in women presenting with metastatic adenocarcinoma in the axillary nodes. This evaluation should include clinical examination and mammography in all cases, and PET and MRI in selected cases. PET and MRI may be particularly useful when considering a breast-conserving surgical procedure.

Adenocarcinoma↗

A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter sepsis.

BACKGROUND/PURPOSE: Chronic vascular access catheters have become an important adjunct to the treatment of children with complex medical diseases, particularly malignancy. One of the major complications of chronic venous access devices is bacterial infection of the catheter site and bloodstream. Infusion of systemic antibiotics directly into the catheter has been the standard initial therapy with failure leading to catheter removal and replacement. It has been suggested by a number of investigators that the addition of urokinase as a thrombolytic agent to lyse any accumulated thrombus or fibrin would increase the successful catheter clearance by antibiotics. This study was designed as a prospective, randomized trial to compare treatment of children with positive catheter blood cultures with either antibiotics alone or in combination with urokinase 5,000 U boluses 12 and 24 hours after study entry. METHODS: A total of 63 patients were entered in the study. Thirty-three received antibiotics and urokinase, and 30 received antibiotics alone. RESULTS: A total of 45 catheters (71%) were cleared of infection and salvaged. Treatment failures leading to catheter removal occurred in 9 of 33 in the experimental group and 9 of 30 in the control population (no significant difference). CONCLUSIONS: Urokinase could not be shown to act as an adjuvant in the clearance of infection from chronic central venous access catheters that had no evidence of clot or thrombus. This study required the performance of a dye study and excluded any patient with a known thrombus. This conclusion must therefore be limited to patients with no evidence of a clot or fibrin sheath.

Anti-Bacterial Agents↗

Successful treatment of stage III neuroblastoma based on prospective biologic staging: a Children's Cancer Group study.

PURPOSE: To identify a biologically favorable and unfavorable subset of patients with Evans stage III neuroblastoma and to determine whether treatment stratification would improve the event-free survival (EFS) for high-risk patients and maintain excellent EFS for the lower-risk patients. PATIENTS AND METHODS: Risk stratification was performed by age, MYCN gene copy number, Shimada histopathologic classification, and serum ferritin level. Lower-risk patients were treated on the less intensive Children's Cancer Group (CCG)-3881, whereas high-risk patients were treated on CCG-3891, which included more intensive multimodality therapy and, in some cases, autologous bone marrow transplantation (ABMT). RESULTS: Of 228 Evans stage III patients entered onto the study, 92% also met the definition of International Neuroblastoma Staging System (INSS) stage 3. One hundred forty-three patients met the lower-risk criteria, which included 89 patients less than 1 year of age and 54 patients 1 year of age or greater, and favorable biology, whereas 85 patients were 1 year of age or greater and biologically unfavorable. Biologically unfavorable patients 1 year of age or greater who underwent gross surgical resection had improved survival, whereas the outcome of infants or biologically favorable older patients did not change according to resection. The EFS rate at 4 years was 100% for the patients with favorable biology of any age, 90% for those less than 1 year of age but with at least one unfavorable characteristic, and 54% for Evans stage III patients 1 year of age or greater with unfavorable biology. Age, ferritin level, MYCN copy number, Shimada histopathology, primary site, and intraspinal extension were significant univariate prognostic factors for all patients, but only MYCN copy number and age were independent factors in multivariate analyses. CONCLUSION: The excellent survival of the biologically favorable group and the historically improved EFS of the biologically unfavorable group suggest that biologic staging should be used to define the prognosis and treatment of stage III neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Congenital diaphragmatic hernia survival and use of extracorporeal life support at selected level III nurseries with multimodality support.

BACKGROUND: Congenital diaphragmatic hernia (CDH) has been cited to have a mortality rate of 50%. There have been multiple studies at individual institutions demonstrating potential benefits from various strategies including extracorporeal life support (ECLS), delayed repair, and lower levels of ventilator support. There has been no multicenter survey of institutions offering these modalities to describe the current use of ECLS and survival of these infants. In addition, the relationship between the number of patients with CDH managed at an individual institution and outcome has not been evaluated. METHODS: We queried 16 level III neonatal intensive care centers on the use of ECLS and survival of infants with CDH who were treated during 2 consecutive years (1993 to 1995). Data are presented as mean +/- SEM, median, and range. RESULTS: Data were collected on 411 patients. Of these, 71% +/- 8% were outborn and 8% +/- 3% were considered nonviable. Overall survival of CDH infants was 69% +/- 4% (range, 39% to 95%). The survival rate of infants on ECLS was 55% +/- 4%, whereas survival of infants not requiring ECLS was significantly increased at 81% +/- 5% (p = 0.005). The mean rate of ECLS use was 46% +/- 2%. There was no correlation between the number of cases per year at an individual institution and overall survival, ECLS survival, or ECLS use (r = 0.341, 0.305, and 0.287, respectively). There was also no correlation between case volume at an individual institution and ECLS survival (r = 0.271). CONCLUSIONS: The current survival rate and rate of ECLS use in infants with CDH at level III neonatal intensive care units in the United States are 69% +/- 4% and 46% +/- 2%, respectively. There is no correlation between the yearly individual center experience with managing CDH and rate of ECLS use or outcome.

Extracorporeal Circulation↗

Surgical ligation of patent ductus arteriosus in very low birth weight infants: is it safe?

We evaluated the outcome of a combined medical and surgical treatment of patent ductus arteriosus (PDA) in newborns weighing less than 1500 g. Charts were retrospectively reviewed for 76 newborns with a PDA between 1993 and 1997. Thirteen infants had pre-existing conditions prohibiting the use of indomethacin; eight were managed surgically, five medically. The remaining 63 infants received indomethacin therapy. Thirty-two medical failures occurred, requiring surgical ligation of the PDA. Those requiring surgery had a lower average birth weight (847 versus 997 g) and gestational age (26 versus 28 weeks; P < 0.05). Indomethacin treatment was successful in 27 infants. There were only three operative complications: a small pneumothorax, wound bleeding, and a small aortic tear. All recovered uneventfully and no deaths were attributable to the surgical procedure itself. There was no difference in the incidence of respiratory distress syndrome, duration of intubation, sepsis, neonatal enterocolitis, renal dysfunction, bleeding disorders, or intraventricular hemorrhage among both groups. Surgical ligation of a PDA is associated with a high success rate, a low incidence of complications, and no additional morbidity than indomethacin alone. We propose that surgical ligation should be regarded as a first line therapy for very small premature infants who are at higher risk of medical failure.

Ductus Arteriosus, Patent↗