Patent ductus arteriosus stenting: ductal dissection and spasm in pulmonary atresia with intact ventricular septum.

Ductal dissection is rarely mentioned but intractable complication of ductal stenting. We demonstrate the dissection image under fluoroscopy and the use of a relatively large stent as an applicable treatment.

The Association of Patent Ductus Arteriosus with Inflammation: A Narrative Review of the Role of Inflammatory Biomarkers and Treatment Strategy in Premature Infants.

Patent ductus arteriosus (PDA) is a common cardiovascular complication that complicates clinical care in the intensive care of premature infants. Prenatal and postnatal infections and the inflammation process can contribute to PDA, and intrauterine inflammation is a known risk factor of PDA. A variety of inflammatory biomarkers have been reported to be associated with PDA. Chorioamnionitis induces the fetal inflammatory process via several cytokines that have been reported to be associated with the presence of PDA and may have a role in the vascular remodeling process or vessel dilation of the ductus. On the other hand, anti-inflammatory agents, such as antenatal steroids, decrease PDA incidence and severity in patients born to those with chorioamnionitis. Proinflammatory cytokines, which are expressed more significantly in preterm neonates and chorioamnionitis, are associated with the presence of PDA. In this review, we focus on the pathogenesis of PDA in preterm infants and the role of biomarkers associated with the perinatal inflammatory process.

Clinical Experience of Transcatheter Closure for Ventricular Septal Defects in Children Weighing under 15 kg.

BACKGROUND: Failure to thrive and poor weight gain are the main problems associated with ventricular septal defects complicated by heart failure in pediatric patients. Recent advances in transcatheter closure have enabled safe and effective interventions in these patients. OBJECTIVES: The purpose of this study was to describe our experience with transcatheter closure of ventricular septal defects in young children with low weight. METHODS: Pediatric patients weighing < 15 kg who underwent transcatheter closure of ventricular septal defects between January 2018 and December 2019 at our hospital were retrospectively enrolled. RESULTS: Twelve patients were enrolled: one with a muscular defect, two with outlet defects, and nine with perimembranous defects. Their median age was 24 (7-60) months, and their median weight before the procedure was 11.8 kg (4.7-14.9 kg; mean Z-score: -1.3). The median precordial echocardiographic defect diameter was 5.6 (2.0-9.3) mm. Successful transcatheter closure was achieved in 11 cases. The mean weight at 1-month follow-up after defect closure was 13.5 kg (6.2-19.8 kg; mean Z-score: -0.2). The mean length of hospitalization was 2.7 days. CONCLUSIONS: This study highlights the potential safety and therapeutic efficacy of transcatheter ventricular septal defect closure in infants with low weight. Considerable weight gain and heart failure symptom attenuation at 1 month after transcatheter closure were observed.

Timing of Endotracheal Intubation in Patients with Fulminant Enterovirus 71 Infection.

Background and objective: Enterovirus 71 (EV 71) infections may result in the rapid progression of cardiopulmonary failure. Early endotracheal intubation is considered to be of primary importance. However, the appropriate timing for this is still not known. The aim of this study is to investigate the timing of intubation of children with fulminant EV71 infection. Material and Methods: From March 1998 to May 2012, patients with severe EV71 infection who were admitted to the pediatric intensive care unit of the National Cheng Kung University Hospital were enrolled in this study. Medical records were retrospectively reviewed. The patients were classified into three groups in accordance with the outcome of intubation. We used rhombencephalitis grading to describe the neurological presentation of these patients. The study was approved by the institutional review board. Results: There were a total of 105 patients enrolled. Of these, 77 patients were in Grade I, and only three of them needed intubation, who were, however, soon extubated within 24 h. There were 10 patients in Grade II; nine of them needed intubation. In total, 18 patients belonged to Grade III, and all of them need to be intubated. We then compared the outcome of intubation of grades II and III. There was only one patient out of the nine patients in grade II who experienced failed extubation due to the progression of the disease. Among grade III patients, only four patients were successfully extubated. We also listed clinical parameters to determine which one could be a sign that indicated intubation. Comparing the favorable outcomes, cranial nerve involvement was a good indicator for the timing of intubation. Conclusions: This study showed that early intubation in Grade II provides favorable outcomes and improves morbidity and mortality. We also found that if cranial nerve involvement was present, then early intubation is indicated.

Efficacy of a Novel Palivizumab Prophylaxis Protocol for Respiratory Syncytial Virus Infection in Congenital Heart Disease: A Multicenter Study.

OBJECTIVE: To analyze the efficacy of a novel palivizumab protocol for hemodynamically significant congenital heart disease (hsCHD) in subtropical areas without clear respiratory syncytial virus seasonality. STUDY DESIGN: Since July 2013, the National Health Insurance program has provided reimbursement for palivizumab prophylaxis with a novel monthly protocol in selected patients with hsCHD under 1 year of age. We performed a multicenter study to assess the trend of respiratory syncytial virus hospitalizations in patients with hsCHD from 2010 to 2016 during the prepalivizumab, transition, and postpalivizumab periods, and compared treatment and propensity-matched control groups. RESULTS: A total of 747 patients were enrolled in the study group and 809 in the control group. The male:female was 836:720. Cyanotic CHD was observed in 42.9% of patients. The mean age at diagnosis of CHD was 32.9 days. After 516 685 patient-days of follow-up and a mean of 3.9 doses of palivizumab in the treatment group, respiratory syncytial virus hospitalization rates decreased by 53% and 49% before and after match compared with the control group (P = .009 and .029, respectively). Hospitalization days and intensive care unit admission rate also decreased similarly in the treatment group. The efficacy of this protocol was more prominent in patients with cyanotic hsCHD. The annual respiratory syncytial virus-associated hospitalization rates also decreased significantly from the prepalivizumab to the palivizumab period (from 4.8% to 2.0%; P = .038). CONCLUSION: Palivizumab prophylaxis through the novel monthly protocol for patients with hsCHD is effective in reducing respiratory syncytial virus-related hospitalizations.

Clinical ultrasound stimulating angiogenesis following drug-release from polymersomes on the ischemic zone for peripheral arterial occlusive disease.

Peripheral Arterial Occlusive Disease (PAOD) is an aging disease that affects the quality of life of many people by its intermittent claudication and critical limb ischemia presentations. Traditional treatment and management of PAOD are asking patients to make a life change and medication with antiplatelet, statins and cilostazol, which decrease the possibility of clot formation. Our strategy has employed a magnetic Fe3O4-PLGA polymersome to carry the cilostazol into the ischemic area by magnetic attraction following remote-control drug release through low-energy ultrasound exposure. In the animal studies, the cilostazol-loaded Fe3O4-PLGA polymersomes were injected and accumulated at ischemic leg through magnetic attraction. Then, using a clinical-use ultrasound machine the leg was irradiated to forward cilostazol release from the accumulated polymersomes. Dramatically, we found an observable result of bloody flux recovery in the leg after 7 days compared to the non-treated leg that showed no evidence of the blood recovery.

Infantile cardiac vascular tumour: from prenatal diagnosis to postnatal treatment.

Primary vascular tumour of the heart is rare, especially in neonates and infants. We report a male premature newborn with a right atrial tumour associated with a large amount of pericardial effusion detected by screening foetal echography. Diagnosis of capillary haemangioma was confirmed by histopathological examination after complete surgical resection. Other vascular tumours in the neonates and infants reported in the English literatures are reviewed, and one algorithm for both prenatal and postnatal management is proposed.

Interventional Transcatheter Closure Ameliorates the Leukocyte Rho Kinase Activities among Patients with Patent Ductus Arteriosus.

BACKGROUND: Patent ductus arteriosus (PDA) causes increased pulmonary blood flow, which can lead to pulmonary arterial hypertension (PAH). Rho-associated coiled-coil containing protein kinase (ROCK) may play an important pathophysiological role in PAH. We hypothesized that the increased pulmonary artery (PA) flow from PDA could activate ROCK. METHODS: Patients who received a PDA transcatheter closure in our hospital were consecutively enrolled in this study. Basic demographics and clinical hemodynamic data of the study participants were recorded. Then, ROCK activity was measured before and after the PDA occlusion procedure. ROCK activity was defined as the phosphorylation ratio of myosin-binding subunit by Western blot measurement. We also sub-divided patients into the coil group and occluder group based on the occlusion device used in each patient's procedure. RESULTS: From January 2009 to December 2011, 25 patients with a median age of 2.3 years, ranging from 10 months to 72 years were enrolled. The mean PDA size was 0.31 ± 0.14 cm, the mean Qp/Qs shunt was 1.54 ± 0.41, and the mean systolic pulmonary artery pressure was 26.9 ± 10.3 mmHg. There were 10 patients (one boy and nine girls) in the coil group and 15 patients (four boys and eleven girls) in the occluder group. Following the closure of the PDA, ROCK activity significantly decreased (1.78 ± 2.25 vs. 0.77 ± 0.69, p < 0.01). There was a strong correlation between the leukocyte ROCK activity with the systolic PA pressure (y = 5.4608x + 22.54, R2 = 0.5539, p < 0.05), but not the Qp/Qs value. Both subgroups showed significant changes of ROCK activity after the procedure. Interestingly, when comparing the coil group with the occluder group, the decrease in ROCK activity was more apparent in the occluder group. CONCLUSIONS: The findings of this study indicated that ROCK activity is higher in patients with PDA and correlates with PA pressure. The decrease in ROCK activity following the device closure suggests that ROCK may be an important biomarker for PDA patency. KEY WORDS: Patent ductus arteriosus (PDA); Pulmonary arterial pressure; Rho kinase; Transcatheter closure.

Case report: Distinct neurologic manifestation and cytokine profile of a child with COVID-19-associated acute fulminant encephalitis.

The neurologic manifestations of coronavirus disease 2019 (COVID-19) may range from mild symptoms such as headache or confusion to profound encephalopathy with variable outcomes and sequelae. Here, we reported a case of fatal COVID-19-associated encephalitis with acute fulminant cerebral edema, presenting first with visual hallucination and then a rapid progression into comatose status in a few hours. Serial brain computed tomography depicted cerebral edematous changes from bilateral ventral temporal lobe to the whole brain leading to brain herniation. Multiple cytokines in serum and cerebrospinal fluid (CSF) were increased, with a more prominent rise in the CSF. Therefore, we postulated a hypothesis regarding the mechanism of this fulminant encephalitis that the SARS-CoV-2 virus attacked ventral temporal lobes initially, triggered a severe cytokine storm, and then led to subsequent disruption of the blood-brain barrier, diffuse brain edema, and brain herniation. The trend of cytokine profiles over time may aid in diagnosing and evaluating the severity and prognosis of COVID-19-associated encephalitis.

Surgical ligation, not transcatheter closure, associated with a higher severity of bronchopulmonary dysplasia in extremely preterm infant intervened for patent ductus arteriosus.

OBJECTIVE: Patent ductus arteriosus (PDA) is a common complication among premature infants, which may be responsible for prematurity-related complications such as bronchopulmonary dysplasia (BPD). It is unclear whether different interventional methods contribute to the severity of BPD, given the original National Institute of Child Health and Human Development (NICHD) 2001 definition. To date, surgical ligation and the transcatheter approach have been equally successful in premature infants with hemodynamically significant PDA after medical treatment failure. Immediate improvement in the respiratory condition has been reported after transcatheter closure. However, the short-term pulmonary outcome has not been clarified yet. METHODS: This retrospective study investigated infants born with a body weight <1000 g and who underwent either surgical ligation or transcatheter closure of PDA in a single tertiary institution. The infants were divided into groups according to the type of procedure (surgical ligation or transcatheter occlusion). The primary outcome was the severity of BPD at discharge or at a postmenstrual age of 36 weeks. The outcome was analyzed with logistic regression. RESULTS: Forty-four patients met the inclusion criteria, of whom 14 underwent transcatheter occlusion and 30 underwent surgical ligation. The overall birth body weights and gestational age ranges were not different. The univariate model revealed an association between the procedure type and BPD severity. After adjusting for confounders, the multivariate model confirmed associations between BPD severity and procedure type and severe respiratory distress syndrome requiring surfactant. CONCLUSION: Compared with the transcatheter approach, surgery for PDA in extremely preterm infants is associated with severe BPD at discharge. Further large-scale studies are needed to determine the exact mechanism.

A Global Perspective on PDA Management in the Extremely Premature: Shifting Trend Toward Transcatheter Closure.

Patent ductus arteriosus (PDA) is a frequently encountered defect in infants born extremely premature (≤26 weeks' gestation). Historically, closure of the PDA was performed using cyclooxygenase inhibitor medications or by surgical ligations. However, the benefits of PDA closure using these therapies have never been demonstrated, albeit studies have previously not focused on the extremely premature infants. Therefore, there was a worldwide trend toward conservative management of the PDA. With improved survival of extremely premature infants, comorbidities associated with the PDA has increased, resulting in finding alternate treatments such as transcatheter patent ductus arteriosus closure (TCPC) for this population. Currently, there is a renewed interest toward selective treatment of the PDA in this high-risk cohort of small infants. This Comprehensive Review article inspects the globally changing trends in the management of the PDA in premature infants, with a special focus on the rising adoption of TCPC. Moreover, this article compiles data from several neonatal networks worldwide to help understand the problem at hand. Understanding the current management of premature infants and their outcomes is fundamentally essential if pediatric cardiologists are to offer TCPC as a viable therapeutic option for this population. This article aims to serve as a guide for pediatric cardiologists on this topic by compiling the results on landmark clinical trials on PDA management and the controversies that arise from these trials. Comparative outcomes from several countries are presented, including interpretations and opinions of the data from experts globally. This is a step toward coming to a global consensus in PDA management in premature infants.

Late recurrence of infra-Hisian complete atrioventricular block.

Acquired complete atrioventricular block that is caused by infectious myocarditis is usually transient and has a favourable outcome. We report the case of a 15-year-old girl who had complete infra-Hisian atrioventricular block due to adeno viral myocarditis and received a permanent pacemaker at the age of 10 months. The pacemaker lost its function at the age of 7 years. However, she experienced a late recurrence of complete atrioventricular block 10 years later. Complete atrioventricular block is rarely recovered if it persisted for 2 weeks. Even in the patients with late recovery, long-term follow-up and pacemaker therapy are still needed.

Transient Congenital Complete Heart Block: A Case Report.

Congenital complete heart block is defined as a complete atrioventricular block occurring prenatally, at birth, or within the first month of life. Congenital complete heart block has a high mortality rate, and in infants with normal heart morphology, it is often associated with maternal connective tissue disease. In these latter cases, neonatal congenital complete heart block is usually irreversible. We present a rare case of a female neonate who had bradycardia noted at a gestational age of 37 weeks. Her mother had no autoimmune disease history. She had no structural heart disease, and the serology surveys for autoantibodies including SSA/Ro and SSB/La were all negative. Without intervention or medication, her congenital complete heart block completely recovered to a normal sinus rhythm within 5 days. The cause of the transient congenital complete heart block was unknown in this case.

Cardiovascular Intervention in Neonates Using an Umbilical Vein Approach.

Cardiovascular catheterization has been applied in infant treatment for several decades. To date, considerable research attention has been paid to cardiovascular catheterization in small neonates. However, peripheral vascular routes of catheterization are possible obstacles for interventionists. Umbilical vein catheterization has been reported as a route for neonates, although few attempts have been made to investigate this approach. This study aimed to retrospectively review cardiovascular intervention using the umbilical vein approach as applied to infants admitted to a tertiary center from 2017 to 2020. Details including the perinatal variables, indication diagnoses, and procedure devices were collected. The enrollment included a total of 16 cases representing 17 intervention events, with infants born at a gestation age of 22-39 weeks and body weight ranging from 478 to 3685 g at the time of the procedure. The postnatal age ranged from 1 to 27 days. The catheter sizes ranged from 4 to 11 Fr. Indications included being admitted for patent ductus arteriosus occlusion (n = 15), balloon pulmonary valvuloplasty (n = 3), balloon atrial septostomy (BAS) (n = 3), pulmonary valve (PV) perforation (n = 1), and two interventions for catheter placement for continuous venovenous hemofiltration. The success rate for cardiovascular catheterization was 88.2% (15/17). There were two patients for which cannulation failed due to ductus venosus closure: one intraabdominal hemorrhage complication during continuous venovenous hemofiltration (CVVH), and one cardiac catheterization failure of PV perforation due to failure to insert the guiding catheter into the right ventricular outflow tract. Based on these findings, we conclude that cardiac catheterization and the placement of a large-sized catheter through an umbilical vein in a small infant represents a safe and time-saving method when catheterization is required.

Potential of Autologous Progenitor Cells and Decellularized Porcine Artery Matrix in Construction of Tissue-engineered Vascular Grafts.

To develop a tissue-engineered vascular graft, we used pericardial effusion-derived progenitor cells (PEPCs) collected from drained fluid after open-heart surgery in children with congenital heart diseases to repopulate a decellularized porcine pulmonary artery. The PEPCs were compared with human fibroblasts (HS68) and human umbilical vein endothelial cells (HUVECs) in cell growth and migration. They were cultured with the matrices via an inner approach (intima), lateral approach (media), and outer approach (adventitia). PEPCs grew and migrated better than the other two cells 14 days after seeding in the decellularized vessel. In immunofluorescence assays, PEPCs expressed CD90 and CD105 indicating a vascular differentiation. PEPCs grew in a decellularized porcine pulmonary artery matrix may have the potential for producing tissue-engineered vascular grafts.

Diastolic and systolic right ventricular diameters for predicting pulmonary hypertension in children with congenital heart disease.

Prospective electrocardiography (ECG)-gated cardiac computed tomography angiography (CTA) is widely used for pediatric patients with congenital heart disease (CHD) due to the lower radiation dose compared with the ECG-gated technique. However, functional parameters acquired using ECG-gated cardiac CT to predict pulmonary hypertension (PH) in children with CHD have not yet been reported. This study aimed to investigate the potential of diastolic and systolic right ventricular diameters (RVD) on prospective ECG-gated cardiac CTA to predict PH in children with CHD. A total of 44 children with CHD were divided into two groups: CHD with PH (n = 22) and CHD without PH (n = 22). The association between ECG-gated CTA parameters and PH was evaluated by logistic regression. The receiver operating characteristic curve (ROC) was used to find the best cut-off point for the parameters measured by Youden's index. Patients with higher RVD-BSA [aOR (95% CI) diastolic: 2.76 (1.23-6.23); systolic: 6.15 (1.72-22.06)] had higher risk of PH after adjusting for age and patent ductus arteriosus. The area under the curve (AUC) of D-RVD-BSA was 0.907 and the AUC of S-RVD-BSA was 0.917. Logistic regression showed that patients with D-RVD-BSA over 6.86 or S-RVD-BSA over 5.87 had significantly higher risk of PH after adjustments (aOR = 23.52, 95% CI = 2.89-191.03; aOR = 31.14, 95% CI = 2.75-352.85). In conclusion, in children with CHD, measurements of diastolic or systolic BSA-modified RVDs on prospective ECG-gated CTA are non-invasive markers of PH. BSA-modified D-RVD of 6.86 or BSA-modified S-RVD of 5.87 may be used to identify PH in children with CHD.

Herbal Extract from Codonopsis pilosula (Franch.) Nannf. Enhances Cardiogenic Differentiation and Improves the Function of Infarcted Rat Hearts.

BACKGROUND: The roots of Codonopsis pilosula (Franch.) Nannf. have been used in traditional Chinese medicine for treating cardiovascular disease. In the current study, we aimed to discover herbal extracts from C. pilosula that are capable of improving cardiac function of infarcted hearts to develop a potential therapeutic approach. METHODS: A mouse embryonic stem (ES) cell-based model with an enhanced green fluorescent protein (eGFP) reporter driven by a cardiomyocyte-specific promoter, the α-myosin heavy chain, was constructed to evaluate the cardiogenic activity of herbal extracts. Then, herbal extracts from C. pilosula with cardiogenic activity based on an increase in eGFP expression during ES cell differentiation were further tested in a rat myocardial infarction model with left anterior descending artery (LAD) ligation. Cardiac function assessments were performed using echocardiography, 1, 3, and 6 weeks post LAD ligation. RESULTS: The herbal extract 417W from C. pilosula was capable of enhancing cardiogenic differentiation in mouse ES cells in vitro. Echocardiography results in the LAD-ligated rat model revealed significant improvements in the infarcted hearts at least 6 weeks after 417W treatment that were determined based on left ventricle fractional shortening (FS), fractional area contraction (FAC), and ejection fraction (EF). CONCLUSIONS: The herbal extract 417W can enhance the cardiogenic differentiation of ES cells and improve the cardiac function of infarcted hearts.

Respiratory Trajectory after Invasive Interventions for Patent Ductus Arteriosus of Preterm Infants.

Invasive interventions have been conducted in preterm infants with significant patent ductus arteriosus (PDA) when medical treatment has failed, and methods of invasive intervention have been reported. Surgical ligation via lateral thoracotomy has been a well-established procedure for decades. Recently, transcatheter occlusion has been safely and feasibly applied to the premature population. However, little research has been conducted on the benefits of transcatheter occlusion in very-low-birth-weight (VLBW) infants compared to surgical ligation. This study compared transcatheter and surgical techniques in VLBW infants in terms of short-term respiratory outcomes. The medical records of 401 VLBW infants admitted to a tertiary hospital between September 2014 and January 2019 were retrospectively reviewed. Patients who were diagnosed with a congenital anomaly, a chromosomal anomaly, or congenital heart disease, except for an inter-atrial shunt, were excluded. The perinatal conditions, neonatal morbidities, periprocedural vital signs, and respiratory support trajectories were compared between the transcatheter-treated and surgically ligated group. A total of 31 eligible VLBW infants received invasive intervention: 14 were treated with transcatheter occlusion (Group A), and 17 infants were treated with surgical ligation (Group B). Respiratory outcomes were not statistically significant between the two groups, despite Group A showing a trend toward early improvement in post-intervention respiratory trajectory. In this small case study, a different trend in post-intervention respiratory trajectories was observed. Future research with larger case numbers should be conducted to address our preliminary observations in more detail.

Synthetic Poly(lactic-co-glycolic Acid) Microvesicles as a Feasible Carbon Monoxide-Releasing Platform for Cancer Treatment.

Biogenic microvesicles (MVs) play a pivotal role in intercellular signal communication, thus initiating critical biological responses such as the proliferation of cancer cells, gene and protein transport, and chemo-drug resistance. In addition, they have been recognized as having great potential in drug delivery applications. However, the productivity of biologically produced MVs is not sufficient for clinical applications. In this study, synthetic poly(lactic-co-glycolic acid) (PLGA) MVs were prepared via a double emulsion method. The PLGA MVs had a biogenic MV-mimic vesicular structure with a hydrophilic core/surface and hydrophobic interior of the shell, showing great potential for drug delivery. We successfully embedded hydrophobic iron carbonyl (IC), a carbon monoxide (CO) donor, in the PLGA shell region, enabling the delivery of IC in an aqueous solution. Because of the intrinsic properties of PLGA, it was susceptible to temperature, and the MVs could easily collapse in a warm environment, leading to the decomposition of IC into CO. The in vitro result indicated that the cell viability of A549 lung carcinoma cells significantly decreased to 14% after treatment with IC-loaded PLGA MVs for 24 h, suggesting that these synthetic PLGA MVs constitute an excellent drug delivery platform.

Massive Gastric Hemorrhage after Indomethacin Therapy: A Rare Presentation and Critical Management in an Extremely Preterm Infant.

Indomethacin has been widely used in preterm infants with hemodynamically significant patent ductus arteriosus (PDA). Gastrointestinal complications of indomethacin have been reported in 5% of treated neonates. However, massive gastric mucosa hemorrhage is a rarely reported complication. To the best of our knowledge, the infant in this report is the smallest reported in the literature to have undergone successful surgery for such a complication. A male preterm infant weighing 566 g was born at 252/7 weeks of gestational age without a complicated maternal history. Soon after birth, he received nasal noninvasive respiratory support and minimal feeding. PDA was observed since the first day of life (DOL), treatments were initiated on the second DOL for the hemodynamical significance, and PDA was closed after two courses of indomethacin therapy (0.2 mg/kg). At midnight on the seventh DOL, generalized pallor, bloody gastric drainage, and a distended stomach were observed. Massive gastric bleeding was suspected. He suffered from intermittent hypotension, which was corrected with blood products and fluid resuscitation under monitoring with a radial arterial line. Gastric lavage with cooling saline was performed twice but in vain. Prior to surgical consultation, intravascular volume transfusion was given twice. An exploratory laparotomy was arranged after obtaining the parents' consent. Blood oozing from the gastric mucosa was observed through gastrostomy and was successfully stopped via epinephrine-soaked gauze compression. After the operation, his clinical course remained uneventful, and he was discharged without neurological anomaly at two-year follow-up. Physicians need to be cautious of indomethacin's effect on platelet dysfunction in preterm infants with multiple predisposing factors. The tendency for mucosal bleeding should be continuously monitored after indomethacin therapy.