Transcatheter balloon angioplasty of internal pulmonary artery bands to improve pulmonary blood flow: a case series.

Pulmonary artery banding (PAB) is used to restrict pulmonary blood flow in select patients with large left-to-right intracardiac shunts or unrestrictive pulmonary blood flow prior to eventual surgical repair or palliation. More recently, surgical placement of an internal or intraluminal PAB (IPAB) has been used to restrict pulmonary circulation. Here we present two patients who underwent balloon angioplasty of the IPAB to treat cyanosis and improve pulmonary blood flow.

Natural remedies for Alzheimer's disease: A systematic review of randomized controlled trials.

Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.

Pre-Fontan Assessment Utilizing Combined Cardiac Catheterization and Cardiac MRI: Comparison to the Pre-Fontan Catheterization.

Single ventricle patients eligible for Fontan completion undergo pre-Fontan catheterization for hemodynamic and anatomic assessment prior to surgery. Cardiac magnetic resonance imaging may be used to evaluate pre-Fontan anatomy, physiology, and collateral burden. We describe our center's outcomes in patients undergoing pre-Fontan catheterization combined with cardiac magnetic resonance imaging. A retrospective review of patients undergoing pre-Fontan catheterization from 10/2018 to 04/2022 at Texas Children's Hospital was performed. Patients were divided into 2 groups: combined cardiac magnetic resonance imaging and catheterization (combined group) and those who underwent catheterization only (catheterization only group). There were 37 patients in the combined group and 40 in the catheterization only group. Both groups were similar in age and weight. Patients undergoing combined procedures received less contrast, and experienced less in-lab time, fluoroscopy time and catheterization procedure time. Median radiation exposure was lower in the combined procedure group but was not statistically significant. Intubation and total anesthesia times were higher in the combined procedure group. Patients undergoing a combined procedure were less likely to have collateral occlusion performed than in the catheterization only group. Bypass time, intensive care unit length of stay, and chest tube duration were similar in both groups at the time of Fontan completion. Combined pre-Fontan assessment decreases catheterization procedure and fluoroscopy time associated with cardiac catheterization at the expense of longer anesthetic times, and results in similar Fontan outcomes compared to when cardiac catheterization alone is utilized.

Extra-cardiac and complex Fontan baffle fenestration using radio frequency current via surgical electrocautery.

BACKGROUND: Fontan baffle punctures and creation of Fontan fenestration for cardiac catheterisation procedures remain challenging especially due to the heavy calcification of prosthetic material and complex anatomy. OBJECTIVES: We sought to evaluate our experience using radiofrequency current via surgical electrocautery needle for Fontan baffle puncture to facilitate diagnostic, electrophysiology, and interventional procedures. METHODS: A retrospective chart review of all Fontan patients (pts) who underwent Fontan baffle puncture using radiofrequency energy via surgical electrocautery from three centres were performed from January 2011 to July 2021. RESULTS: A total of 19 pts underwent 22 successful Fontan baffle puncture. The median age and weight were 17 (3-36 years) and 55 (14-88) kg, respectively. The procedural indications for Fontan fenestration creation included: diagnostic study (n = 1), atrial septostomy and stenting (n = 1), electrophysiology study and ablation procedures (n = 8), Fontan baffle stenting for Fontan failure including protein-losing enteropathy (n = 7), and occlusion of veno-venous collaterals (n = 2) for cyanosis. The type of Fontan baffles included: extra-cardiac conduits (n = 12), lateral tunnel (n = 5), classic atrio-pulmonary connection (n = 1), and intra-cardiac baffle (n = 1). A Fontan baffle puncture was initially attempted using traditional method in 6 pts and Baylis radiofrequency trans-septal system in 2 pts unsuccessfully. In all pts, Fontan baffle puncture using radiofrequency energy via electrocautery needle was successful. The radiofrequency energy utilised was (10-50 W) and required 1-5 attempts for 2-5 seconds. There were no vascular or neurological complications. CONCLUSIONS: Radiofrequency current delivery using surgical electrocautery facilitates Fontan baffle puncture in patients with complex and calcified Fontan baffles for diagnostic, interventional, and electrophysiology procedures.

Co-administration of saffron and chamomile: to determine the efficacy as an adjuvant therapy for mild to moderate depression in human subjects. A pilot randomized clinical trial.

OBJECTIVE: To determine the combined effects of chamomile and saffron herbs as an adjuvant therapy in patients with metabolic alterations associated with mild to moderate depression. METHODS: The prospective, randomised, blinded, end-point pilot study was conducted at the Aga Khan University, Karachi, from August to October 2020, and comprised patients with mild to moderate depression with or without diabetes, hypertension and dyslipidaemia. The subjects were randomised into intervention group A, which was given herbal tea sachets containing saffron 1mg and chamomile 20mg for twice a day oral use for a month along with medications, and control group B, which was advised to continue their routine medications. Data was collected at baseline and post-intervention using Patient Health Questionnaire-9 for assessing depression severity, and blood samples for cholesterol estimations. Data was analysed using SPSS 20. RESULTS: Of the 50 subjects, 25(50%) were in each of the two groups. Cholesterol, high-density lipoprotein, low-density lipoprotein and depression values were significantly better in group A than in group B (p<0.05). CONCLUSIONS: Potential benefits of combined doses of chamomile and saffron were found in depressive patients by improving metabolic alterations.

Interactions of Apigenin and Safranal with the 5HT1A and 5HT2A Receptors and Behavioral Effects in Depression and Anxiety: A Molecular Docking, Lipid-Mediated Molecular Dynamics, and In Vivo Analysis.

BACKGROUND: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. METHODS: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. RESULTS: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. CONCLUSIONS: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.

A narrative review on manifestations of gluten free casein free diet in autism and autism spectrum disorders.

Autism and Autism Spectrum Disorder (ASD) are specific neurological disorders that affect the brain, frequently characterised by challenging paediatric behaviour. The current narrative review using PubMed and Google Scholar was conducted in line with the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and comprised randomised controlled trials and clinical control trials with gluten-free, casein-free (GFCF) diets published till 2020. Of the 80 studies selected, 7(8.75%) were included in the review. It was observed that the gluten-free, casein-free diet was safe with therapeutic benefits in autistic children. Therefore, a tailored dietary approach can be a beneficial management regimen. The trials related to utility of gluten-free, casein-free diet among autistic children are sparse, with limited sampling size, and indication of bias in the findings. Therefore, larger cohort studies on gluten-free, casein-free trials are required to provide further insight into the therapeutic benefits of the diet.

Inhibition and disruption of amyloid formation by the antibiotic levofloxacin: A new direction for antibiotics in an era of multi-drug resistance.

Neurodegenerative diseases are a group of debilitating maladies involving protein aggregation. To this day, all advances in neurodegenerative disease therapeutics have helped symptomatically but have not prevented the root cause of the disease, i.e., the aggregation of involved proteins. Antibiotics are becoming increasingly obsolete due to the rising multidrug resistance strains of bacteria. Thus, antibiotics, if put to different use as therapeutics against other diseases, could pave a new direction to the world of antibiotics. Hence, we studied the antibiotic levofloxacin for its potential anti-amyloidogenic behavior using human lysozyme, a protein involved in non-systemic amyloidosis, as a model system. At the sub-stoichiometric level, levofloxacin was able to inhibit amyloid formation in human lysozyme as observed by various spectroscopic and microscopic methods, with IC50 values as low as 8.8 ± 0.1 µM. Levofloxacin also displayed a retarding effect on seeding phenomena by elongating the lag-phase (from 0 to 88 h) at lower concentration, and arresting lysozyme fibrillation at the lag stage in sub-stoichiometric concentrations. Structural and computational analyses provided mechanistic insight showing that levofloxacin stabilizes the lysozyme in the native state by binding to the aggregation-prone residues, and thereby inhibiting amyloid fibrillation. Levofloxacin also showed the property of disrupting amyloid fibrils into a smaller polymeric form of proteins which were less cytotoxic as confirmed by hemolytic assay. Therefore, we throw new light on levofloxacin as an amyloid inhibitor and disruptor which could pave way to utilization of levofloxacin as a potential therapeutic against non-systemic amyloidosis and neurodegenerative diseases.

The Role of K-Ras and P53 in Biliary Tract Carcinoma.

OBJECTIVE: To focus mainly on the role of proto-oncogene Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras) and tumour-suppressor gene p53 which are among the most commonly mutated genes in biliary tract carcinomas. METHODS: The systematic review comprised research articles published between 2002 and 2019 on PubMed and Google Scholar databases which were searched using the terms 'TP53', 'K-Ras', 'mutation', 'biliary tract carcinoma', 'cholangiocarcinoma', and 'murine model'. Repetitions, duplicates and irrelevant articles were excluded. No data was retrieved from posters, presentations and symposiums, and experiments involving bile aspirations were also excluded. RESULTS: Of the 72 articles reviewed, 11(15.3%) were included. Of them, 3(27.3%) studies, conducted in China, Japan and Taiwan, reported a positive correlation between K-Ras mutation and biliary tract carcinoma. Only 1(9%) study, conducted in China, showed the sole correlation between p53 inactivation and biliary tract carcinoma. Also, 4(36.4%) studies, conducted in China, Japan and Europe, showed a positive association of both K-Ras mutation and p53 inactivation with biliary tract carcinoma. CONCLUSIONS: K-Ras and p53 mutation both contribute to biliary tract carcinoma. K-Ras mutation, however, has a much higher frequency compared to p53 inactivation in such cancers.

SAPIEN S3 valve deployment in the pulmonary position using the gore DrySeal sheath to protect the tricuspid valve.

BACKGROUND: Tricuspid valve injury can occur during implantation of a SAPIEN valve in the pulmonary position. We describe our experience using a long Gore DrySeal (GDS) sheath to protect the tricuspid valve during advancement of the Commander delivery system. METHODS: Retrospective single center review of all patients who underwent placement of a SAPIEN valve in the right ventricular outflow tract between January 2016 and April 2020. Patients were divided into two groups: delivery of the valve using standard technique (Group I), and with the use of a GDS (Group II), for comparison. RESULTS: There were 48 patients in total: 25 in Group I and 23 in Group II. In Group II, the first 10 patients had a 29 mm S3 placed through a 26 French (Fr), 65 cm GDS. We then performed additional crimping of the S3 onto the balloon after the balloon catheter was withdrawn to position the valve on the balloon outside the body. Subsequently, seven had a 29 mm S3 placed through a 24 Fr GDS, and four had a 26 mm S3 placed through a 22 Fr GDS including one weighing 16 kg. Two had a 23 mm S3 placed through a 22Fr GDS as the 20Fr GDS was not available in our lab. Severe tricuspid valve injury occurred in 2/25 (8%) of Group I patients and 0/23 of Group II patients. CONCLUSION: Use of a long GDS may protect the tricuspid valve from injury during implantation of the S3 valve in the pulmonary position, and is technically feasible in smaller patients.

Application of transcatheter valves for aortic valve replacement in pediatric patients: A case series.

OBJECTIVES: To describe our initial experience with pediatric transcatheter aortic valve replacement. BACKGROUND: Transcatheter aortic valve replacement (TAVR) has been approved and used to treat calcific aortic stenosis in adult patients. Select pediatric patients with congenital heart disease (CHD) who are poor candidates for conventional surgical aortic valve replacement can benefit from TAVR. METHODS: A retrospective review was performed to identify and describe pediatric patients with CHD who underwent transcatheter or hybrid aortic valve replacement using a Melody Valve (Medtronic, Minneapolis, MN), or Sapien S3/XT valve (Edwards Life sciences LLC, Irvine, CA). Patients in whom transcatheter valves were implanted on cardiopulmonary bypass were included. Imaging data, procedural elements, and clinical follow-up data were collected to evaluate acute and short-term results. RESULTS: A total of eight pediatric patients underwent treatment of aortic valvular disease using balloon expandable valves and delivery systems. Two patients had Melody valve implantation and six received a Sapien valve (one XT/five S3). In one patient, a Melody valve was placed surgically, failed, and was replaced with a Sapien valve 2 years later. Two patients were treated using a standard transfemoral route, four had the valve delivered on cardiopulmonary bypass via a median sternotomy, one was placed with a transapical approach, and one via a carotid cut down. Patients were followed for an average 16 months (range 1-208 weeks). There were no early or late deaths in this cohort. There were no embolic events, and all valves worked well in the immediate postoperative period. Both Melody implants developed moderate to severe regurgitation at 2 years and 4 years, respectively, and both required replacement at that time. One Sapien 3 valve developed a paravalvular leak that required reintervention within 6 months of implantation. CONCLUSIONS: Transcatheter valves offer a reasonable alternative to traditional surgical aortic valve replacement in certain pediatric patients who are suboptimal surgical candidates. Hybrid approaches and valve delivery on cardiopulmonary bypass has been used in smaller patients. Long-term performance of these valves in young patients has not been studied.

Comparison of drug eluting versus bare metal stents for pulmonary vein stenosis in childhood.

OBJECTIVE: Comparison of outcomes using bare metal (BMS) and drug-eluting (DES) stents in pulmonary vein stenosis (PVS). BACKGROUND: PVS is a serious condition with frequent restenosis after surgical and percutaneous interventions. After experiencing encouraging results with DES, we sought to compare outcomes of BMS and DES in native and post-surgical PVS. METHODS AND RESULTS: A retrospective review of all patients who underwent stent implantation between 08/93 and 11/17 for PVS at Texas Children's Hospital was performed. BMS were used to treat 58 lesions in 37 patients and 105 DES used to treat 105 lesions in 41 patients. Mean age at first stent implant was 2.9 ± 3.5 years in BMS and 16.2 ± 18.8 months in DES group. Of those with follow-up catheterization, mean lumen loss rate from stent implant to first follow-up catheterization was 0.85 ± 1.47 mm/month over 6.4 ± 6.4 months in the BMS group (n = 44 lesions) compared to 0.16 ± 0.31 mm/month over 6.8 ± 7.4 months in the DES group (n = 86 lesions), p < .01. Follow-up for the BMS group was 14 months (6 days-22.3 years), with 13 mortalities, eight lesions were re-stented and six complete occlusions were noted. Follow-up for DES group (including four cross-overs) was 17.5 months (3 days-9 years), with 10 mortalities, seven lesions were re-stented, 11 had complete occlusion, 20 new adjacent lesions in the same vessel underwent stenting and 12 stents were intentionally fractured. CONCLUSION: DES have significantly lowered lumen loss rate when compared to BMS at medium term follow-up and can be fractured to enable larger diameters. Availability of larger diameter DES would be ideal.

Technical factors are associated with complications and repeat intervention in neonates undergoing transcatheter right ventricular decompression for pulmonary atresia and intact ventricular septum: results from the congenital catheterisation research collaborative.

BACKGROUND: Transcatheter right ventricle decompression in neonates with pulmonary atresia and intact ventricular septum is technically challenging, with risk of cardiac perforation and death. Further, despite successful right ventricle decompression, re-intervention on the pulmonary valve is common. The association between technical factors during right ventricle decompression and the risks of complications and re-intervention are not well described. METHODS: This is a multicentre retrospective study among the participating centres of the Congenital Catheterization Research Collaborative. Between 2005 and 2015, all neonates with pulmonary atresia and intact ventricular septum and attempted transcatheter right ventricle decompression were included. Technical factors evaluated included the use and characteristics of radiofrequency energy, maximal balloon-to-pulmonary valve annulus ratio, infundibular diameter, and right ventricle systolic pressure pre- and post-valvuloplasty (BPV). The primary end point was cardiac perforation or death; the secondary end point was re-intervention. RESULTS: A total of 99 neonates underwent transcatheter right ventricle decompression at a median of 3 days (IQR 2-5) of age, including 63 patients by radiofrequency and 32 by wire perforation of the pulmonary valve. There were 32 complications including 10 (10.5%) cardiac perforations, of which two resulted in death. Cardiac perforation was associated with the use of radiofrequency (p=0.047), longer radiofrequency duration (3.5 versus 2.0 seconds, p=0.02), and higher maximal radiofrequency energy (7.5 versus 5.0 J, p<0.01) but not with patient weight (p=0.09), pulmonary valve diameter (p=0.23), or infundibular diameter (p=0.57). Re-intervention was performed in 36 patients and was associated with higher post-intervention right ventricle pressure (median 60 versus 50 mmHg, p=0.041) and residual valve gradient (median 15 versus 10 mmHg, p=0.046), but not with balloon-to-pulmonary valve annulus ratio, atmospheric pressure used during BPV, or the presence of a residual balloon waist during BPV. Re-intervention was not associated with any right ventricle anatomic characteristics, including pulmonary valve diameter. CONCLUSION: Technical factors surrounding transcatheter right ventricle decompression in pulmonary atresia and intact ventricular septum influence the risk of procedural complications but not the risk of future re-intervention. Cardiac perforation is associated with the use of radiofrequency energy, as well as radiofrequency application characteristics. Re-intervention after right ventricle decompression for pulmonary atresia and intact ventricular septum is common and relates to haemodynamic measures surrounding initial BPV.

Transposition of the great arteries: When echocardiography does not match the clinical picture.

Aortopulmonary window (APW) is a rare form of congenital heart disease seen in isolation or with complex cardiac lesions. APW has been associated with other cardiac defects such as interrupted aortic arch and Tetralogy of Fallot, but few cases have been reported of APW associated with transposition of the great arteries (TGA). In a newborn with TGA and intact ventricular septum, diagnosis of APW requires a high index of suspicion. This article reviews the literature on TGA with APW and illustrates the importance of additional evaluation in neonates with TGA when oxygen saturation and PaO2 do not match predicted clinical values.

Efficacy and safety of catheter-based rheolytic and aspiration thrombectomy in children.

BACKGROUND: Vascular thromboses are a significant cause of morbidity and mortality in children. Data in children regarding catheter-based rheolytic and aspiration thrombectomy systems are limited. We sought to review the safety and efficacy of catheter-based rheolytic and aspiration thrombectomy systems in children. METHODS: Data of all children having undergone thrombectomy using specialized rheolytic or aspiration systems were reviewed. RESULTS: Thrombectomy was performed in 50 vessels in 21 patients, median age 1.9 months (8 days-18 yrs), median weight 4.3 (1.1-67.9) kg. Thrombectomy was performed using AngioJet in 16, Helix Clot Buster in 5, Fetch catheter in 8, Pronto catheter in 1, and a combination of other systems in 20 vessels (with AngioJet in 16). Thrombectomy was successful in 47/50 (94%) vessels in 18/21 (86%) patients with additional balloon/stent therapy or tPA administration performed in 16/18 (89%) of these patients. There were 2 (9.5%) major complications (both with AngioJet) consisting of asystole when thrombectomy was performed using activation times of >5 sec. At a median follow-up of 10 months (2 weeks-7 years), all 47 successfully treated vessels are patent, with 8/18 (44%) patients requiring reintervention with angioplasty/stent placement or repeat thrombectomy. CONCLUSIONS: Catheter-based thrombectomy systems are an important adjunctive tool in the treatment of children with thrombotic vessel occlusions. Significant hemodynamic compromise seen when using AngioJet may be minimized by using activation times of ≤5 sec. © 2016 Wiley Periodicals, Inc.

The effect of resident duty-hours restrictions on internal medicine clerkship experiences: surveys of medical students and clerkship directors.

UNLABELLED: PHENOMENON: Medical students receive much of their inpatient teaching from residents who now experience restructured teaching services to accommodate the 2011 duty-hour regulations (DHR). The effect of DHR on medical student educational experiences is unknown. We examined medical students' and clerkship directors' perceptions of the effects of the 2011 DHR on internal medicine clerkship students' experiences with teaching, feedback and evaluation, and patient care. APPROACH: Students at 14 institutions responded to surveys after their medicine clerkship or subinternship. Students who completed their clerkship (n = 839) and subinternship (n = 228) March to June 2011 (pre-DHR historical controls) were compared to clerkship students (n = 895) and subinterns (n = 377) completing these rotations March to June 2012 (post-DHR). Z tests for proportions correcting for multiple comparisons were performed to assess attitude changes. The Clerkship Directors in Internal Medicine annual survey queried institutional members about the 2011 DHR just after implementation. FINDINGS: Survey response rates were 64% and 50% for clerkship students and 60% and 48% for subinterns in 2011 and 2012 respectively, and 82% (99/121) for clerkship directors. Post-DHR, more clerkship students agreed that attendings (p =.011) and interns (p =.044) provided effective teaching. Clerkship students (p =.013) and subinterns (p =.001) believed patient care became more fragmented. The percentage of holdover patients clerkship students (p =.001) and subinterns (p =.012) admitted increased. Clerkship directors perceived negative effects of DHR for students on all survey items. Most disagreed that interns (63.1%), residents (67.8%), or attendings (71.1%) had more time to teach. Most disagreed that students received more feedback from interns (56.0%) or residents (58.2%). Fifty-nine percent felt that students participated in more patient handoffs. INSIGHTS: Students perceive few adverse consequences of the 2011 DHR on their internal medicine experiences, whereas their clerkship director educators have negative perceptions. Future research should explore the impact of fragmented patient care on the student-patient relationship and students' clinical skills acquisition.