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The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) oversee pharmaceutical regulations, including orphan drugs targeting rare diseases with limited patient populations. Post-marketing studies are crucial for monitoring safety and efficacy, with post-marketing requirements (PMRs) mandated by the regulatory agencies to ensure compliance. This study aims to compare PMR statuses, objectives, and pivotal trial characteristics of orphan drugs approved by the FDA (n = 154) and EMA (n = 79) from 2008 to 2018, shedding light on regulatory differences and their impact on drug development. Contrary to expectations, our analysis found no significant disparity in the proportion of orphan drugs with and without PMRs approved by both the FDA (48.1%) and EMA (55.7%). Safety concerns surrounding orphan drugs post-approval, attributed partly to pivotal trial design, underscore the need for robust post-marketing surveillance. While the FDA primarily focuses on post-marketing safety (36.1%), the EMA places a higher emphasis on both efficacy and safety (47.1%), reflecting distinct approaches to PMR management between the two regulatory bodies. The observed trend of delayed PMRs at the EMA (47.1%) highlights the importance of effective cooperation between regulators and pharmaceutical companies to ensure the timely completion of PMRs and enhance drug safety.
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Sinus venosus atrial septal defects (SVASDs), concurrent with partial anomalous pulmonary venous connections (PAPVCs), are a rare congenital heart disease in dogs. Surgical correction is essential when clinical signs or significant hemodynamic changes are present. We aimed to report on the successful surgical correction of an SVASD with PAPVCs, using a computed tomography (CT)-based customized 3D cardiac model. A 10-month-old male poodle was referred for corrective surgery for an ASD. Echocardiography confirmed a hemodynamically significant left-to-right shunting flow through an interatrial septal defect and severe right-sided heart volume overload. For a comprehensive diagnosis, a CT scan was performed, which confirmed an SVASD with PAPVCs. A customized 3D cardiac model was used for preoperative decision-making and surgical rehearsal. The defect was repaired using an autologous pericardial patch under a cardiopulmonary bypass (CPB). Temporary pacing was applied for sinus bradycardia and third-degree atrioventricular block. The patient recovered from the anesthesia without further complications. The pacemaker was removed during hospitalization and the patient was discharged without complications 2 weeks post-surgery. At the three-month follow-up, there was no shunting flow in the interatrial septum and the right-sided volume overload had been resolved. The cardiac medications were discontinued, and there were no complications. This report indicates the validity of surgical correction under CPB for an SVASD with PAPVCs, and the advantages of utilizing a CT-based 3D cardiac model for preoperative planning to increase the surgical success rate.
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Del-Nido cardioplegia (DNc) is a single-dose cardioplegia that is widely used in human medicine because of its long duration. In this report, we describe two cases of open-heart surgery with cardiopulmonary bypass (CPB) using DNc. One dog was diagnosed with partial atrioventricular septal defect, and the other dog was diagnosed with myxomatous mitral valve disease stage D. Both dogs were treated with open-heart surgery with DNc to induce temporary cardiac arrest. No complications from DNc were observed, and the patients were discharged. Veterinary heart surgeons should consider DNc as an option for temporary cardiac arrest during open-heart surgery with CPB.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Doenças do Cão , Parada Cardíaca , Humanos , Cães , Animais , Soluções Cardioplégicas , Parada Cardíaca Induzida/veterinária , Procedimentos Cirúrgicos Cardíacos/veterinária , Parada Cardíaca/veterinária , Estudos Retrospectivos , Doenças do Cão/cirurgiaRESUMO
Sternal cleft is a rare malformation with significant morbidity and mortality. It has been associated with other midline fusion defects, most significantly Cantrell's pentalogy, involving the sternum, pericardium, heart, diaphragm, and abdominal wall. This study reported a successfully managed case of a newborn with a total sternal cleft and Cantrell's pentalogy. A review of literature and pertinent management principles was also conducted.
Assuntos
Cardiopatias Congênitas , Pentalogia de Cantrell , Cardiopatias Congênitas/cirurgia , Humanos , Recém-Nascido , Anormalidades Musculoesqueléticas , Pentalogia de Cantrell/diagnóstico , Pentalogia de Cantrell/cirurgia , Pericárdio/anormalidades , Pericárdio/cirurgia , Esterno/anormalidades , Esterno/cirurgiaRESUMO
The recent rise in minimally invasive cardiovascular procedures is being accompanied by an increase in related complications. We report on an acute type A aortic dissection performed in an 82-year-old man 1 week after staged 'zone 0' hybrid thoracic endovascular aortic repair (TEVAR). Previously, the patient had undergone type I hybrid arch debranching and staged 'zone 0' TEVAR for an aortic arch aneurysm. 'Zone 0' TEVAR after type I hybrid debranching might increase the risk for aortic injury on the residual native aorta and should, therefore, be closely followed up to enable the early diagnosis of complications.
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We report two cases of severe mediastinitis accompanied by abscess due to endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), that were successfully treated by effective surgical drainage. A 68-year-old woman was referred to our hospital due to chest discomfort and high fever after EBUS-TBNA, and a 54-year-old man was referred due to general weakness, chills, and high fever after the same procedure. Both were diagnosed with EBUS-related mediastinitis and discharged after surgical treatment. Similar to previous reports, the importance of surgical procedures for mediastinitis caused by EBUS-TBNA was suggested. Further research and establishment of guidelines on this matter is necessary.
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BACKGROUND: Bleeding remains the chief concern during extracorporeal membrane oxygenation (ECMO). Recently, several studies proposed nafamostat mesilate (NM) as an alternative anticoagulant to heparin due to reduced bleeding complications and comparable thromboembolic episodes. The aim of this study was to evaluate the clinical outcomes of ECMO anticoagulated mainly with NM. METHODS: This was a retrospective observational case series of patients who were placed on ECMO between January 2011 and December 2017 at Chungnam National University Hospital. The main outcomes were bleeding and thromboembolic episodes. RESULTS: During the study period, a total of 91 ECMO runs on 87 patients were identified. There were 54 veno-venous runs and 37 veno-arterial runs. Among the 87 patients, 47 (54.0%) patients were successfully weaned and 29 (33.3%) survived to discharge. Most of the runs were anticoagulated with NM (n=68, 74.7%), followed by heparin (n=22, 24.2%) and argatroban (n=1, 1.1%). The mean duration of ECMO support was 11.3±11.1 days. The overall incidence of bleeding was 46.2% (n=42); 26 runs were anticoagulated with NM (26/68, 38.2%) and 16 with heparin (16/22, 72.7%) (P=0.005). The overall incidence of thromboembolic episodes was 12.1% (n=11). In the NM group, the incidence of hyperkalemia requiring any type of intervention was 17.6% (n=12). CONCLUSIONS: In this single center study, NM appears to be associated with fewer bleeding complications during ECMO without increasing the incidence of thromboembolic episodes.
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A bronchogenic cyst causing cardiac tamponade is a rare condition. We report an unusual case of a bronchogenic cyst that caused cardiac tamponade. A 49-year-old female patient presented at our emergency room with complaints of palpitations and shortness of breath that had lasted for 5 days preceding the visit. Echocardiography revealed a very large cystic mass compressing the left a trium posteriorly, and a large amount of pericardial effusion caused the diastolic collapse of the ventricles. Atrial fibrillation and aggravated dyspnea were observed, and the patient's vital signs were unstable after admission. We therefore performed an emergency operation. The bronchogenic cyst was resected by thoracotomy and the patient was discharged 12 days after the operation without any complications over 5 years of follow-up.
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Herein, we report on a family with Carney complex. Four members of the family underwent a total of 11 open heart operations as well as 9 other operations to treat extrathoracic masses. All the family members met at least 2 major clinical criteria and 1 supplemental criterion. We analyzed their genomic loci, including the protein kinase A regulatory subunit 1 gene. The results revealed no specific mutations, except for a common single nucleotide polymorphism. This case series of Carney complex emphasizes the importance of close longitudinal follow-up because of the high rate of tumor recurrence irrespective of the site. Clinicians should not overlook the specific features of familial myxoma.
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Isolated anomalous right coronary artery originating from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly that is asymptomatic and discovered incidentally in most cases. ARCAPA is generally not considered a fatal defect in infancy or childhood, although cases of sudden death have been reported. Here, we report a 2-month-old female infant who presented with a prolonged fever that was determined to be caused by rhinovirus infection. Myocardial ischemia of the left ventricular posterior wall was already seen on echocardiography, and ARCAPA was discovered incidentally. The patient underwent successful surgical reimplantation of the right coronary artery to the aortic root to re-establish dual ostial circulation.
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With advancements in complex repairs in neonates with complicated congenital heart diseases, extracorporeal membrane oxygenation (ECMO) has been increasingly used as cardiac support. ECMO has also been increasingly used for low birth weight (LBW) or very low birth weight (VLBW) neonates. However, since prematurity and LBW are risk factors for ECMO, the appropriate indications for neonates with LBW, especially VLBW, are under dispute. We report a case of ECMO performed in a 1,360-g premature infant with VLBW due to cardiopulmonary bypass weaning failure after repairing infracardiac total anomalous pulmonary venous return.
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A 50-year-old female patient with visual disturbances was referred for further evaluation of a heart murmur. Fundoscopy revealed a Roth spot in both eyes. A physical examination showed peripheral signs of infective endocarditis, including Osler nodes, Janeway lesions, and splinter hemorrhages. Our preoperative diagnosis was subacute bacterial endocarditis with severe aortic regurgitation. The patient underwent aortic valve replacement and was treated with intravenous antibiotics for 6 weeks postoperatively. The patient made a remarkable recovery and was discharged without complications. We report this case of subacute endocarditis with all 4 classic peripheral signs in a patient who presented with visual disturbance.
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BACKGROUND: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. METHODS: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. RESULTS: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. CONCLUSION: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.
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BACKGROUND: Video-assisted thoracoscopic surgery (VATS) pulmonary wedge resection has emerged as the standard treatment for primary spontaneous pneumothorax. Recently, single-port VATS has been introduced and is now widely performed. This study aimed to evaluate the outcomes of the Tower crane technique as novel technique using a 15-mm trocar and anchoring suture in primary spontaneous pneumothorax. METHODS: Patients who underwent single-port VATS wedge resection in Chungnam National University Hospital from April 2012 to March 2014 were enrolled. The medical records of the enrolled patients were reviewed retrospectively. RESULTS: A total of 1,251 patients were diagnosed with pneumothorax during this period, 270 of whom underwent VATS wedge resection. Fifty-two of those operations were single-port VATS wedge resections for primary spontaneous pneumothorax performed by a single surgeon. The median age of the patients was 19.3±11.5 years old, and 43 of the patients were male. The median duration of chest tube drainage following the operation was 2.3±1.3 days, and mean postoperative hospital stay was 3.2±1.3 days. Prolonged air leakage for more than three days following the operation was observed in one patient. The mean duration of follow-up was 18.7±6.1 months, with a recurrence rate of 3.8%. CONCLUSION: The tower crane technique with a 15-mm trocar may be a promising treatment modality for patients presenting with primary spontaneous pneumothorax.
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A 61-year-old man was diagnosed with aortic stenoinsufficiency with periannular abscess, which involved the aortic root of noncoronary sinus (NCS) that invaded down to the central fibrous body, whole membranous septum, mitral valve (MV), and tricuspid valve (TV). The open complete debridement was executed from the aortic annulus at NCS down to the central fibrous body and annulus of the MV and the TV, followed by the left ventricular outflow tract reconstruction with implantation of a mechanical aortic valve by using a leaflet of the half-folded elliptical bovine pericardial patch. Another leaflet of this patch was used for the repair of the right atrial wall with a defect and the TV.
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BACKGROUND: The management of tetralogy of Fallot, pulmonary atresia, and major aortopulmonary collateral arteries is controversial because of the wide variability of pulmonary artery (PA) and major aortopulmonary collateral arteries morphology. Several different staged strategies have been used to promote growth of diminutive PA branches. We have preferred a right ventricular (RV)-PA homograft for symmetrical growth of the central PA branches. In this study we evaluated the success of this strategy. METHODS: Between 2006 and 2012, 23 patients with pulmonary atresia and diminutive PAs underwent RV-PA homograft implantation. Median age was 2 months (range, 4 days to 18 months), and median body weight was 5.1 kg (range, 1.7 to 8.5 kg). The type of homograft was aortic in 8, pulmonary in 6, and femoral vein in 9. The mean diameter of the homograft was 10.5 mm (range, 6 to 16 mm). All procedures were performed on cardiopulmonary bypass. The PA diameter was measured at the time of the operation and subsequent catheterization. RESULTS: The median size of the branch PA was 2.1 mm. In the 18 patients who had serial assessment of PA size, the right PA increased by 307% ± 184%, the left PA increased by 283% ± 139%, and the Nakata index increased from 28.8 ± 20.1 mm(2)/m(2) to 253 ± 96 mm(2)/m(2) during a median period of 347 days (range, 44 to 1,520 days). The PA growth ratio (PA growth in mm/mo) was similar between the right PA (0.42 ± 0.46 mm/mo) and the left PA (0.43 ± 0.47 mm/mo). There was no acute conduit failure. Seventeen patients required 28 percutaneous interventions for embolization of an aortopulmonary collateral or stenosis of the conduit or PA. There were no hospital deaths. Three patients died late after other procedures during a mean follow-up of 44.7 months. Twenty patients (87%) have undergone complete repair to date. CONCLUSIONS: RV-PA homograft implantation can be performed in neonates and infants with minimal risk of acute occlusion. The RV-PA homograft promotes rapid and balanced growth of central pulmonary arteries leading to complete repair in most patients.