Comparison of 5-year safety and efficacy of laser photocoagulation and intravitreal bevacizumab injection in retinopathy of prematurity.

PURPOSE: To compare laser photocoagulation and intravitreal injection of bevacizumab (IVB) treatment for retinopathy of prematurity (ROP). METHODS: The study included 52 eyes of 26 patients after ROP treatment who were observed up to 5 years of age. Twenty-eight eyes received laser photocoagulation as the initial treatment (laser group), and twenty-four eyes underwent IVB (IVB group). We collected data on gestational age, birth weight, 1- and 5-min Apgar scores, zone and stage at the time of treatment, recurrence of ROP and best-corrected visual acuity (BCVA) (logMAR), equivalent spherical value (SE), ocular complications, and developmental delay at the age of 5. RESULTS: More zone I low-stage eyes were treated with IVB than laser. There was no difference in BCVA (p = 0.836). Although the mean SE was not different between the groups (p = 0.280), the prevalence of myopia was significantly higher in the laser group (p = 0.020). Developmental delay was observed in 3 of 14 and 3 of 12 cases in the laser and IVB groups, respectively (p = 0.596). Retinal holes were observed in 2 eyes in the IVB group, with 1 developing localized retinal detachment. There were no significant differences between the groups in the other factors. CONCLUSIONS: Compared to laser for ROP, IVB was not inferior in neurodevelopment or visual outcome and was superior in refractive error. As cases in the IVB group showed retinal holes, long-term follow-up with fundus examination is recommended after IVB.

The mid-term outcome of Fontan conversion compared with primary total cavopulmonary connection.

BACKGROUND: The indication of Fontan conversion (FC) from atriopulmonary connection (APC) to total cavopulmonary connection (TCPC) is unclear. We sought to analyze the mid-term outcome of prophylactic and therapeutic Fontan conversion compared with that of primary TCPC. METHODS: Patients with a univentricular heart who underwent cardiac catheterization at >18 years of age between July 2005 and July 2019 were included and divided into three groups: symptomatic APC patients who underwent therapeutic FC (t-FC, n = 13), asymptomatic APC patients after prophylactic FC (p-FC, n = 15), and patients who had primary TCPC procedure (pTCPC, n = 24). RESULTS: The mean last follow up was at the age of 32.0 ± 7.8, 26.8 ± 3.8, and 27.3 ± 7 years (p = 0.07) in t-FC, p-FC, and pTCPC, respectively. There was no late death. All of t-FC and 12 (80%) of p-FC cases underwent concomitant arrhythmic surgery. Consequently, five and four patients in t-FC and p-FC groups required pacemaker implantations mostly due to sinus node dysfunction. Thromboembolism was seen in 2 cases in both t-FC (15%) and p-FC (13%), and 1 case in pTCPC (4%) (p = 0.50). The last cardiac catheterization was performed at the age of 29.5 ± 8.5, 24.6 ± 3.8, and 26.3 ± 7.1 years (p = 0.11) in t-FC, p-FC, and pTCPC patients, respectively. There was no significant difference in central venous pressure, aortic pressure, and cardiac index among the three groups. There was no late supraventricular tachyarrhythmic event seen in t-FC and p-FC, whereas two patients in pTCPC had newly developed atrial flutter. CONCLUSIONS: FC is a safe and feasible procedure to bring APC patients back onto the same track of primary TCPC patients in terms of hemodynamics as well as arrhythmia. The antiarrhythmic procedure should be carefully chosen because sinus node dysfunction can frequently occur and FC itself would reduce the risk of arrhythmia.

Pediatric Medical Devices　- Survey of Pediatric Cardiologists and Cardiovascular Surgeons in Japan.

Background: In Japan, the choice of pediatric medical devices is limited because of 2 "device lag" problems: Japan lags behind the USA and Europe in device development, and development of pediatric devices lags behind that of adult devices. We aimed to identify the problems with and impediments to pediatric medical device development as recognized by pediatric physicians in Japan. Methods and Results: A voluntary survey of pediatric medical devices for all council members of the Japanese Society of Pediatric Cardiology and Cardiac Surgery was conducted in 2019. The response rate was 47.1% (154/327). The respondents were 115 pediatric cardiologists (74.7%) and 39 cardiovascular surgeons (25.3%). Approximately 90% believed that difficulties in development existed. Approximately 70% were dissatisfied with the pediatric medical devices currently available in Japan, which was a result of the unavailability of medical devices approved overseas, few types and sizes, and off-label use. Factors that hindered the development of pediatric medical devices included anatomical issues specific to children with congenital heart disease, as well as system issues such as lack of corporate profitability, development cost, and amount of time for development. Conclusions: Pediatric cardiologists and cardiovascular surgeons regard "device lag" and "off-label use" in Japan as important hindrances to the delivery of better medical care for pediatric patients with congenital heart disease.

Short-term intraocular pressure changes after intravitreal injection of bevacizumab for retinopathy of prematurity.

PURPOSE: To evaluate the short-term changes in intraocular pressure (IOP) after intravitreal injection of bevacizumab (IVB) in premature infants with retinopathy of prematurity (ROP). STUDY DESIGN: Prospective cohort study. METHODS: Twenty-two eyes of 11 premature infants with ROP were evaluated. The control eyes were from adults who received an intravitreal injection of antivascular endothelial growth factor agent. The patients received a 0.025 mL (0.625 mg) IVB for the ROP. The IOP was measured with a rebound tonometer at baseline, immediately after the injection, and at 5, 10, 15, 20, and 30 minutes after the injection. The clinical data were collected. The main outcome measures were the IOP values at baseline, immediately after the injection, and at 5, 10, 15, 20, and 30 minutes after the injection. RESULTS: The mean IOP values at baseline, immediately after the injection, and at 5, 10, 15, 20, and 30 minutes after the injection were 12.3 ± 3.0, 40.1 ± 10.7, 20.8 ± 5.1, 15.1 ± 4.8, 11.9 ± 3.2, 9.9 ± 2.6, and 8.8 ± 2.1 mmHg, respectively. The IOP was significantly higher at 5 minutes after the injection (P < .01); however, the pressure in all the eyes normalized (< 21 mmHg) within 15 minutes. None of the clinical parameters, including axial length, was correlated with a high IOP after IVB. CONCLUSION: In premature infants with ROP, IVB is tolerable in terms of the short-term elevation in IOP, which returned to a safe range (< 21 mmHg) within 15 minutes of the injection in all the patients. Consecutive IOP measurement might not be necessary after IVB in premature infants with ROP.

Case report: Atrioventricular block after transcatheter atrial septal closure using the Figulla® Flex II ASD occluder.

We report a 7-year-old male patient who developed severe atrioventricular block after transcatheter closure of the atrial septal defect with an Occlutech Figulla® Flex II ASD occluder (FSO). He had a small aortic rim and the defect measuring 22.3 mm by balloon sizing. When a 24 mm FSO was deployed, he developed Wenckebach second-degree heart block; however, it recovered to sinus rhythm. Hence, the device was implanted. The rhythm deteriorated to a fixed 2:1 heart block within 7 hr. He underwent surgical retrieval of the device and closure of the defect. Intraoperative findings demonstrated the right atrium disk compressing the triangle of Koch, resulting in a small hematoma. The rhythm recovered completely by 7 days after the surgery. Care must be taken when a relatively large device is deployed in a patient with small rims as even "soft and flexible" device like the FSO can injure the endocardium.

A case of new PCDH12 gene variants presented as dyskinetic cerebral palsy with epilepsy.

Here we report a Japanese patient with new compound heterozygous truncating variants in the PCDH12 gene. As compared to the previously reported families who had congenital microcephaly, intrauterine growth retardation, intracranial calcification, and neonatal seizure associated with dysplasia of the midbrain-hypothalamus-optic tract, the present patient showed no midbrain-hypothalamus dysplasia or congenital/postnatal microcephaly, but dyskinetic cerebral palsy and severe intellectual disability as well as multifocal epilepsy. To understand phenotypic spectrum associated with PCDH12 variants, more reports are needed.

Intraoperative hemodynamics monitoring in a patient with pheochromocytoma multisystem crisis: a case report.

BACKGROUND: Pheochromocytoma is a rare catecholamine-secreting tumor. To evaluate the intraoperative hemodynamics with precision is difficult. CASE PRESENTATION: A 42-year-old man, who suddenly developed a life-threatening pheochromocytoma multisystem crisis that occurred during preoperative prophylactic medication, underwent urgent bilateral adrenalectomy. For the purpose of evaluating the intraoperative hemodynamics, we monitored both pulmonary artery catheter-based cardiac output (PACO) and arterial pressure-based cardiac output (APCO; FloTrac™). APCO fluctuated in poor agreement with the change in PACO, especially in the state of cytokine storming. CONCLUSIONS: Overall, the value of stroke volume variation derived from FloTrac™ changed in tandem with the intraoperative volume status, indicating its utility as a marker of circulatory hemodynamics.

The Utility of Decision Trees in Oncofertility Care in Japan.

PURPOSE: To identify the utility and issues associated with the use of decision trees in oncofertility patient care in Japan. METHODS: A total of 35 women who had been diagnosed with cancer, but had not begun anticancer treatment, were enrolled. We applied the oncofertility decision tree for women published by Gardino et al. to counsel a consecutive series of women on fertility preservation (FP) options following cancer diagnosis. Percentage of women who decided to undergo oocyte retrieval for embryo cryopreservation and the expected live-birth rate for these patients were calculated using the following equation: expected live-birth rate = pregnancy rate at each age per embryo transfer × (1 - miscarriage rate) × No. of cryopreserved embryos. RESULTS: Oocyte retrieval was performed for 17 patients (48.6%; mean ± standard deviation [SD] age, 36.35 ± 3.82 years). The mean ± SD number of cryopreserved embryos was 5.29 ± 4.63. The expected live-birth rate was 0.66. CONCLUSIONS: The expected live-birth rate with FP indicated that one in three oncofertility patients would not expect to have a live birth following oocyte retrieval and embryo cryopreservation. While the decision trees were useful as decision-making tools for women contemplating FP, in the context of the current restrictions on oocyte donation and the extremely small number of adoptions in Japan, the remaining options for fertility after cancer are limited. In order for cancer survivors to feel secure in their decisions, the decision tree may need to be adapted simultaneously with improvements to the social environment, such as greater support for adoption.

Pulmonary flow study predicts survival in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

BACKGROUND: We hypothesized that mean pulmonary artery pressure (PAP) detected on a pulmonary flow study may predict medium-term survival and right ventricular systolic pressure (RVSP) in patients with pulmonary atresia (PA), ventricular septal defect (VSD), and major aortopulmonary collateral arteries (MAPCAs). METHODS: Fifty patients with PA/VSD/MAPCAs underwent unifocalization between 2000 and 2013, and 40 of these patients had a pulmonary flow study since 2003. Predictability of the mean PAP on VSD status, medium-term survival, reintervention, and RVSP were analyzed. RESULTS: Forty-seven of the 50 patients (94%) had complete unifocalization at a median age of 11 months (range, 1-194 months), and 37 patients (74%) achieved VSD closure. Among the 40 patients who underwent a pulmonary flow study, the VSD was closed in 34 (85%), with salvage VSD fenestration in 4 (10%), and was intentionally left open in 6 (15%). Survival was 85.5% at 1 year and 78.5% at 5 years. A mean PAP ≥25 mm Hg was associated with worse survival (P = .011). Cox regression analysis identified a mean PAP ≥25 mm Hg as the sole predictor for death (P = .037). Patients with an open VSD had an increased risk of reoperation (P = .001) and pulmonary artery reintervention (P = .010), and had a trend toward increased risk of death (P = .059), compared with those with a closed VSD. CONCLUSIONS: PAP obtained from the intraoperative pulmonary flow study is associated with medium-term survival and late RVSP in patients with PA/VSD/MAPCAs. VSD closure for patients with a mean PAP ≥25 mm Hg on a flow study is considered high risk, and sensible judgment and a low threshold for VSD fenestration are required.

Vicious circle between progressive right ventricular dilatation and pulmonary regurgitation in patients after tetralogy of Fallot repair? Right heart enlargement promotes flow reversal in the left pulmonary artery.

BACKGROUND: The left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation (PR) in patients after tetralogy of Fallot (TOF) repair, but the mechanism of this difference is not well understood. This study aimed to analyze the interplay between heart and lung size, mediastinal geometry, and differential PR. METHODS: Forty-eight Cardiovascular Magnetic Resonance (CMR) studies in patients after TOF repair were analyzed. In addition to the routine blood flow and ventricular volume quantification cardiac angle between the thoracic anterior-posterior line and the interventricular septum, right and left lung areas as well as right and left hemithorax areas were measured on an axial image. Statistical analysis was performed to compare flow parameters between RPA and LPA and to assess correlation among right ventricular volume, pulmonary blood flow parameters and lung area. RESULTS: There was no difference between LPA and RPA diameters. The LPA showed significantly less total forward flow (2.49 ± 0.87 L/min/m(2) vs 2.86 ± 0.89 L/min/m(2); p = 0.02), smaller net forward flow (1.40 ± 0.51 vs 1.89 ± 0.60 mL/min/m(2); p = <0.001), and greater regurgitant fraction (RF) (34 ± 10 % vs 43 ± 12 %; p = 0.001) than the RPA. There was no difference in regurgitant flow volume between RPA and LPA (p = 0.29). Indexed right ventricular end-diastolic volume (RVEDVi) correlated with LPA RF (R = 0.48, p < 0.001), but not with RPA RF (p = 0.09). Larger RVEDVi correlated with a more leftward cardiac axis (R = 0.46, p < 0.001) and with smaller left lung area (R = -0.58, p < 0.001). LPA RF, but not RPA RF, correlated inversely with left lung area (R = -0.34, p = 0.02). The follow-up CMRs in 20 patients showed a correlation of the rate of RV enlargement with the rates of LPA RF worsening (R = 0.50, p = 0.03), and of increasing left lung compression (R = -0.55, p = 0.012). CONCLUSION: An enlarged and levorotated heart is associated with left lung compression and impaired flow into the left lung.

Preventive effect of recombinant human lactoferrin in a rabbit preterm delivery model.

OBJECTIVE: Lactoferrin, an iron-binding glycoprotein found in cervical mucus and amniotic fluid, plays a defensive role against mucosal infections. This study examined the effect of recombinant human lactoferrin on preterm delivery in a rabbit model. STUDY DESIGN: Anesthetized rabbits were randomly assigned to receive either inoculation with Escherichia coli or saline solution and to receive treatment with or without recombinant human lactoferrin inserted into the cervix 2 hours before bacterial inoculation (condition A: saline + saline; condition B: E coli + saline; condition C: E coli + recombinant human lactoferrin). E coli , saline solution, and recombinant human lactoferrin were inserted into the cervix using a hysteroscope and a sterile polyethylene cannula. Fetus survival rate and days to delivery after inoculation were monitored and tumor necrosis factor-alpha concentrations were measured in maternal serum and amniotic fluid. RESULTS: Fetus survival for conditions A, B, and C were 95.7%, 0%, and 32.6%, respectively, whereas pregnancy continuation was 7.00 +/- 0 days, 3.25 +/- 0.43 days, and 4.85 +/- 1.77 days, respectively. CONCLUSION: Cervical recombinant human lactoferrin administration increased fetal survival and extended pregnancy. Lactoferrin has an anti-inflammatory action as well as an antibacterial action, suggesting that recombinant human lactoferrin has the potential to prevent preterm delivery originating from cervical infection in the clinical setting.