Deciphering the host genetic factors conferring susceptibility to severe COVID-19 using exome sequencing.

The COVID-19 pandemic remains a significant public health concern despite the new vaccines and therapeutics. The clinical course of acute SARS-CoV-2 infection is highly variable and influenced by several factors related to the virus and the host. Numerous genetic studies, including candidate gene, exome, and genome sequencing studies, genome-wide association studies, and other omics efforts, have proposed various Mendelian and non-Mendelian associations with COVID-19 course. In this study, we conducted whole-exome sequencing on 90 unvaccinated patients from Turkey with no known comorbidities associated with severe COVID-19. Of these patients, 30 had severe, 30 had moderate, and 30 had mild/asymptomatic disease. We identified rare variants in genes associated with SARS-CoV-2 susceptibility and pathogenesis, with an emphasis on genes related to the regulation of inflammation, and discussed these in the context of the clinical course of the patients. In addition, we compared the frequencies of common variants between each group. Even though no variant remained statistically significant after correction for multiple testing, we observed that certain previously associated genes and variants showed significant associations before correction. Our study contributes to the existing literature regarding the genetic susceptibility to SARS-CoV-2. Future studies would be beneficial characterizing the host genetic properties in different populations.

Percutaneous Closure of Hemodynamically Significant Postoperative Residual Ventricular Septal Defects.

The experience with percutaneous closure of postoperative residual ventricular septal defects (VSDs) is expanding with improved device technology and techniques. To report our experience with percutaneous closure of residual VSDs after cardiac surgeries. Retrospective clinical data review of patients who had percutaneous closure of postoperative residual VSDs at our institution between 2010 and 2022. Patients' demographics, procedural, and follow-up data were looked at. Twelve patients (50% males) with a median age of 9.2 years (range 0.9-22) were identified. Baseline surgeries were 8 tetralogy of Fallot corrections, 2 pulmonary bandings for large muscular VSD (mVSD) including 1 coarctation repair, 1 atrioventricular septal defect repair, 1 sub-aortic membrane resection-induced iatrogenic VSD, 1 isolated VSD closure, and 1 additional mVSD. Median duration between baseline surgery and percutaneous VSD closure was 2.2 years (range 0.2-8.3). Residual VSD shunting was secondary to surgical patch leakage in 8/12 patients. The median angiographic defect diameter was 6.8 mm (range 4.8-14). The defect was balloon-calibrated in 3/12 patients. Defects were tackled retrogradely in 3/9 patients. Amplatzer Membranous VSD occluder (n = 1), Lifetech Multifunctional (n = 5), Membranous (n = 1) and muscular VSD occluders (n = 2) and Occlutech Membranous (n = 1) and Muscular (n = 2) VSD occluders were used. The procedure was successful in 10/12 patients. Two devices embolized to the pulmonary artery and were snare-retrieved. Both patients were referred for surgery. The median follow-up was 1.3 years (range 0.1-12). Six-month ultrasound showed one trivial residual shunt and one mild right ventricular outflow obstruction. One patient is receiving targeted therapy for pulmonary hypertension at 2 years of follow-up. Transcatheter closure of postoperative residual VSDs is a feasible yet challenging intervention. Procedural complications can be encountered.

One-Year Follow-Up Results of MIS-C Patients with Coronary Artery Involvement: A Multi-center Study.

Multisystem inflammatory syndrome (MIS-C) in children is a rare complication of SARS-CoV-2 infection. Knowing the course of the affected or unaffected coronary arteries in the patients under follow-up is important in terms of defining the long-term prognosis of the disease and determining the follow-up plan. This is a multicenter and retrospective study. The data were obtained from nine different centers. Between May 2020 and August 2022, 68 of 790 patients had coronary artery involvement. One-year echocardiographic data of 67 of 789 MIS-C patients with coronary artery involvement were analyzed. Existing pathologies of the coronary arteries were grouped as increased echogenicity, dilatation and aneurysm according to Z scores, and their changes over a 1-year period were determined. The data of all three groups are defined as frequency. SPSS Statistics version 22 was used to evaluate the data. In our study, aneurysm was observed in 16.4%, dilatation in 68.7% and increased echogenicity in 13.4% of the patients. All of the patients with involvement in the form of increased echogenicity recovered without sequelae by the end of the first month. No progression to aneurysm was observed in any of the patients with dilatation. No new-onset involvement was observed in patients with previously healthy coronary arteries during the convalescent period. In addition, from the sixth month follow-up period, there was no worsening in the amount of dilatation in any of the patients. At least 94% of the patients who completed the 12th month control period returned to normal.

Piccolo in transcatheter PDA closure multi-centre study from premature to adolescent children.

In this multi-centre study, the mid- to long-term efficacy and safety of the Amplatzer Piccolo Occluder in patent ductus arteriosus closure in premature and term infants as well as children were discussed. Methods. Between 2016 and 2021, 645 patients, 152 of whom were less than 1 month old, underwent ductus closure with the Piccolo device from five different centres in Turkey. The median age of the patients was 2.2 years, and the mean narrowest point of duct diameter was 1.8 mm. Sixty-two patients weighed ≤ 1.5 kg, 90 patients 1.5-3 kg, and the mean follow-up was 20.4 months. In 396, the duct was closed by the retrograde route. Ductal anatomy was Type A in 285, C in 72, E in 171, and F in 64 patients. Fluoroscopy duration was 6.2 min. The procedure success rate was 99.1%. Device embolisation occurred in 13 patients (2%), and 11 were retrieved with a snare. Cardiac perforation and death developed in one premature baby. The left pulmonary artery and the descending aorta stenosis were observed in 3 (0.4%) and in 5 patients (0.5%). Results. Piccolo device is safe and effective in closing ductus in all age groups. It has low profile for use in premature and newborn babies, a small embolisation risk, and a low residual shunt rate after closure. Conclusion. The Piccolo device can be considered as close an ideal occluder. The lower profile, smaller delivery catheter size, and symmetry of this device allow for a venous or arterial approach.

Iatrogenic perforation of atrial appendage and successful closure with Amplatzer Piccolo Occluder, in a 1-year-old patient.

We present the successful transcatheter closure of the perforation of the cardiac wall from atrial appendage in a 1-year-old girl. Although open-heart surgical repair has been the primary option, percutaneous device closure should always be considered before surgery.

Consensus Guidelines for the Prevention and Management of Periprocedural Complications of Transcatheter Patent Ductus Arteriosus Closure with the Amplatzer Piccolo Occluder in Extremely Low Birth Weight Infants.

Transcatheter closure of patent ductus arteriosus (PDA) in premature infants is a feasible, safe, and an effective alternative to surgical ligation and may be performed with an implant success rate of 97%. Major procedural complications related to transcatheter PDA closure in extremely low birth weight (ELBW) infants are relatively infrequent (< 3%) ,but may be associated with a fatality if not optimally managed. Operators performing transcatheter PDA closures should be knowledgeable about these potential complications and management options. Prompt recognition and treatment are often necessary to avoid serious consequences. With strict guidelines on operator training, proctoring requirements, and technical refinements, transcatheter PDA closure in ELBW infants can be performed safely with low complication rates. This article summarizes the consensus guidelines put forward by a panel of physicians for the prevention and management of periprocedural complications of transcatheter PDA closure with the Amplatzer Piccolo Occluder in ELBW infants.

Transcatheter Treatment of a Symptomatic Giant Iliac Artery Aneurysm with a BeGraft Peripheral Stent in a 2-Year-Old Child.

A 2-year-old girl presented with severe abdominal pain due to a giant iliac artery aneurysm. We embolized the internal iliac artery with microcoils and then eliminated the aneurysmal sac using a BeGraft peripheral stent without any complications. To the best of our knowledge, there are no previous reports of a transcatheter giant iliac artery intervention.

Determination of dynamic thiol/disulphide homeostasis in children with tetralogy of Fallot and ventricular septal defect.

Oxidative stress may contribute to the pathogenesis of congenital heart defects, but the role of dynamic thiol/disulphide homeostasis has not been evaluated. The objective of this study was to assess whether there are changes in thiol/disulphide homeostasis and nitric oxide levels in children with tetralogy of Fallot (TOF) and ventricular septal defect (VSD). A total of 47 children with congenital heart defects (24 TOF and 23 VSD) and 47 healthy age- and sex-matched controls were included in this study. Serum total thiol and native thiol levels were measured using a novel automatic spectrophotometric method. The amount of dynamic disulphide bonds and related ratios were calculated from these values. Serum nitric oxide levels were detected using a chemiluminescence assay. We found that the average native thiol, total thiol, and disulphide levels were decreased in patients with VSD when compared with healthy individuals (p < 0.001, p < 0.001, and p < 0.01, respectively). While native thiol levels were decreased (p < 0.01), disulphide levels were elevated in the TOF group (p < 0.05). We observed marked augmentation of disulphide/native thiol (p < 0.001) and disulphide/total thiol ratios (p < 0.01) in the TOF group. However, there was a significant decrease in native thiol/total thiol ratio in patients with TOF. No significant changes in these ratios were noted in the VSD group. We detected significant elevations in serum nitric oxide levels in children with TOF and VSD (p < 0.001 for all). These results are the first to demonstrate that thiol/disulphide homeostasis and nitric oxide are associated with TOF and VSD in children.

Serum prolidase level in patients with brucellosis and its possible relationship with pathogenesis of the disease: a prospective observational study

Background/aim: Changes in collagen metabolism and fibroblastic activity may play a role in the pathogenesis of brucellosis. The prolidase enzyme plays an important role in collagen synthesis. We aimed to investigate the association of prolidase levels with brucellosis. Materials and methods: Serum prolidase levels in 20 patients newly diagnosed with brucellosis were compared with levels in 30 healthy control subjects. Patients with brucellosis were reassessed 3 months later for prolidase, other laboratory measurements, and response to treatment. Results: The levels of serum prolidase were significantly higher in brucellosis patients compared with those of healthy controls. Prolidase, sedimentation, and C-reactive protein levels were significantly lower after antibrucellosistreatment than before treatment. Conclusion: The current study is the first to demonstrate significantly increased serum prolidase levels in patients with brucellosis compared with healthy controls. Prolidase levels also significantly decreased with antibrucellosis treatment. This finding provides a new experimental basis to understand the pathogenesis of brucellosis in relation to collagen metabolism. The increase in serum prolidase levels might be related to several factors such as tissue destruction, increased fibroblastic activity, and granuloma formation, all of which are involved in the natural history of brucellosis.

Techniques for transcatheter retrieval of the occlutech ASD device United Kingdom-European multicenter report.

AIMS: To gather current experience in Occlutech ASD device retrieval, to determine whether snaring is an effective technique and to highlight alternative retrieval techniques; METHODS AND RESULTS: United Kingdom and European Occlutech ASD device implanters reported their experience in dealing with device embolization and retrieval. Six operators reported 12 retrieval cases. Retrieval was successful in 92% (11/12), although in most cases it was not straightforward and required multiple attempts using different techniques and equipment. When each different technique or equipment combination was considered separately, there were a total of 23 retrieval attempts. Fifteen attempts involved snaring the ball on the right atrial disc of the device ("the RA pin"). In 12/15 of these attempts the snare slipped off the RA pin. In 8/15 attempts snaring eventually failed. In two cases retrieval was facilitated by elongating the device in a blood vessel. In three cases retrieval was achieved by grasping the RA pin with the jaws of the Occlutech Flex II delivery cable; CONCLUSIONS: Snares do not grip the RA pin sufficiently to reliably retrieve the device. Funnelling the device into a blood vessel or grasping the RA pin with the jaws of the delivery cable may be successful alternatives. © 2016 Wiley Periodicals, Inc.

Severe cardiac involvement in Gaucher type IIIC: a case report and review of the literature.

Gaucher disease is an autosomal-recessive lysosomal storage disease characterised by the accumulation of glucocerebroside in macrophages; it is caused by mutations in glucocerebrosidase gene-1 in many organ tissues such as the liver, spleen, and bone marrow. Its different clinical subtypes, according to the presence and severity of neurological symptoms, are as follows: type I, non-neuronopathic (95%); type II, acute neuronopathic; and type III, chronic neuronopathic. Type IIIC is a rare subgroup characterised by cardiovascular involvement as well as eye-movement disorders and late-onset neurological symptoms. In such cases, homozygous D409H is the most frequently detected mutation. In this article, we report the case of a patient, aged 15 years and 8 months, with complaints of syncope and a diagnosis of type IIIC Gaucher disease.

Closure of Secundum Atrial Septal Defects by Using the Occlutech Occluder Devices in More Than 1300 Patients: The IRFACODE Project: A Retrospective Case Series.

BACKGROUND: The Occlutech Figulla ASD device series (OFSO) shows an improved device design for interventional ASD closure, larger follow-up series are missing. METHODS: We retrospectively reviewed the feasibility, safety, implantation properties, results, and follow-up of ASD closure using Occlutech devices over a 5 year period by establishing a multi-institutional collaborative result registry with 16 contributing centers from 11 countries (IRFACODE). RESULTS: In 1315 patients of all age groups (female 66.9%), successful (98%) ASD closure was performed (mean age 28.9 years, weight 52 kg, height 148.6 cm). Of the defects, 47.9% showed no or only a deficient aortic rim; in 11.9%, there was more than one defect; a septum aneurysm was present in 21.5%; and the mean implanted device size was 20.5 mm. Immediate closure was achieved in 78.6%, at discharge in 83.1%, and 96.4% and 97.3% at 6 and 12 months follow-up, respectively. During a mean follow-up of 2.7 years (in total 3597 patient years), significant complications were minimal (total = 8, <1%) with secondary device embolizations in five and AV-blocks in three patients. No erosion or death was reported. CONCLUSION: ASD closure using OFSO is feasible in a large variety of patients, safe with only a minimal risk of severe side effects and especially without any aortic erosions despite a large percentage of large and complicated defects. © 2016 Wiley Periodicals, Inc.

Short-Term Outcomes of Patent Ductus Arteriosus Closure With New Occlutech® Duct Occluder: A Multicenter Study.

AIM: Over the past 2 decades, transcatheter occlusion of patent ductus arteriosus (PDA) with coils and the duct occluders evolved to be the procedure of choice. A new device, the Occlutech PDA® occluder (ODO) device has been designed. Herein, we aimed to evaluate the characteristics and short-term results of patients who underwent transcatheter closure of PDA using the ODO. METHODS: We reviewed the clinical records of 60 patients from different centers in Turkey between December 2013 and January 2016. The medical records were reviewed for demographic characteristics and echocardiographic findings. Device size was selected on the narrowest diameter of PDA. RESULTS: The median patient age was 2.5 years (6 months-35 years), and median PDA diameter was 2.5 mm (1.2-11 mm). Fifty-eight of 60 patients (96.6%) had successful ODO implantation. The occlusion rates were 37/58 (63.7%) at the end of the procedure, 51/58 (87.9%) at 24-48 hours post-procedure, and 57/58 (98.2%) on echocardiography at a median follow-up of 7.6 months. CONCLUSION: Our results indicate that transcatheter closure of PDA using the ODO is effective. Larger studies and longer follow-up are required to assess whether its shape and longer length make it superior to other duct occluders in large, tubular, or window-type ducts. (J Interven Cardiol 2016;29:325-331).

Plasma microRNA profiling of children with idiopathic dilated cardiomyopathy.

CONTEXT: Dilated cardiomyopathy (DCM) is the most common cardiomyopathy in children. MicroRNAs (miRNA) are small RNAs which have regulatory functions in many biological processes. OBJECTIVE: We aimed to determine miRNA expression levels in plasma of children with DCM. MATERIALS AND METHODS: Plasma expression levels of 379 miRNAs were compared between 23 DCM and 26 healthy children. RESULTS: The expression levels of miR-618, miR-875-3p, miR-205, miR-194, miR-302a, miR-147, and miR-544 were found decreased. The expression levels of miR-518f and miR-454 were found increased in DCM patients. DISCUSSION: miRNA level differences may provide the chance of using these miRNAs as new biomarkers.

Serum prolidase level in ankylosing spondylitis: low serum levels as a new potential gold standard biomarker for disease activity.

Ankylosing spondylitis (AS) is a chronic inflammatory disorder that mainly affects the sacroiliac joints and axial skeleton. The aim of this study was to assess serum prolidase level (SPL) and its association with disease activity in patients with AS. This prospective study included 75 AS patients. Thirty age- and gender-matched healthy controls were enrolled. AS patients were considered as active if BASDAI score was ≥4 or inactive if BASDAI score was <4. There were 34 AS patients in the active group and 41 AS patients in the inactive group. Anti-TNF-monoclonal antibody treatment was started in patients in the active group. These active patients were reassessed 6 months later. BASDAI, ASDAS, visual analogue scale, short-form-general health survey questionnaire, C-reactive protein, erythrocyte sedimentation rate and SPL were measured in all AS patients before and after treatment. The SPL was significantly lower in inactive AS patients than in control group, and also, SPL was significantly lower in active AS patients than in inactive patients. All activity parameters were successful in separating active and inactive AS patients. However, the only parameter that could distinguish active patients from inactive patients was prolidase. The optimum cutoff point of SPL to identify patients with active AS was 23.13 ng/mL with sensitivity, specificity, positive predictive value and negative predictive value of 100 %. Serum prolidase level was successful in measuring disease activity and had as high sensitivity and specificity as BASDAI and was superior to other activity parameters.

Evaluation of P-Wave Dispersion, Diastolic Function, and Atrial Electromechanical Conduction in Pediatric Patients with Subclinical Hypothyroidism.

AIM: This study aimed to evaluate ventricular diastolic dysfunction, inter- and intraatrial conduction delay, and P-wave dispersion in pediatric patients with subclinical hypothyroidism. METHODS: The study comprised a total of 30 pediatric patients with subclinical hypothyroidism (SH) (mean age 7.8 ± 3.2 years) and 30 healthy children (mean age 8.4 ± 3.6 years) as the control group. A SH diagnosis was made in the event of increased serum thyroid-stimulating hormone (TSH) and decreased serum free triiodothyronine (T3 ) and free thyroxine (T4 ) concentrations. RESULTS: Conventional Doppler imaging (TDI) showed low mitral early diastolic E-wave velocity and E/A ratio (P < 0.001) and significantly higher mitral late diastolic A-wave velocity (P = 0.001) in hypothyroidism patients. Moreover, patients with hypothyroidism had significantly lower left ventricular (LV) septal Em velocity and Em /Am ratios compared with the control group (P < 0.001), whereas Am velocity was higher in hypothyroidism patients (P = 0.018). LV lateral Em velocity and Em /Am ratio were significantly lower in patients with hypothyroidism compared with the control group (P < 0.001). With regard to atrial electromechanical conduction, atrial electromechanical delay (PA) lateral, PA septum, PA tricuspid, and each of interatrial and intraatrial conduction delay were significantly prolonged in hypothyroidism patients as compared with the control group (P < 0.001, P < 0.001, P = 0.023, P = 0.002, and P = 0.003, respectively). P-wave dispersion was significantly different in the pediatric patients with hypothyroidism (P < 0.001). CONCLUSION: This study demonstrated atrial electromechanical conduction delay, abnormal P-wave dispersion, and ventricle diastolic dysfunction in pediatric patients with hypothyroidism.

Retrieval of an intra-cardiac embolised very long wire via transhepatic access from a war victim child.

We present the case report of a war victim child with severe burn scars, orthopnoea, and dyspnoea due to diffuse pulmonary thromboembolism. During ICU stay, a central venous catheter's 45-mm wire embolised into the heart. The embolised wire was successfully removed via transhepatic access through the creation of an artificial simple snare.

Effects of Vitamin D treatment on thyroid autoimmunity.

BACKGROUND: Vitamin D was shown to be related to autoimmune thyroid diseases (AITDs) in the previous studies. We aimed to investigate the relationship between Vitamin D and thyroid autoimmunity. MATERIALS AND METHODS: Eighty-two patients, diagnosed with AITD by the endocrinology outpatient clinic, were included in this prospective study. All of the patients had both AITD and Vitamin D deficiency, defined as serum values <20 ng/mL. They were randomly assigned into two groups. The first group included 46 patients and the second one included 36 patients. The first group was treated with Vitamin D for 1 month at 1000 IU/day. The second group served as the control group and was not treated with Vitamin D replacement. Serum thyroid-stimulating hormone, free T4 (fT4), thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), and Vitamin D levels were measured at the initiation of the study and again at 1 month in all patients. RESULTS: Two groups were similar with regard to age, sex, and type of thyroid disease. Whereas TPO-Ab (before; 278.3 ± 218.4 IU/ml and after; 267.9 ± 200.7 IU/ml) and TgAb (before; 331.9 ± 268.1 IU/ml and after; 275.4 ± 187.3 IU/ml) levels were significantly decreased by the Vitamin D replacement therapy in group 1 (P = 0.02, P = 0.03, respectively), the evaluated parameters in the control group did not significantly change (P = 0.869, P = 0.530, respectively). In addition, thyroid function tests did not significantly change with Vitamin D replacement in two groups. CONCLUSION: Vitamin D deficiency may contribute to the pathogenesis of AITDs. Since supplementation of the Vitamin D decreased thyroid antibody titers in this study in Vitamin D deficient subjects, in the future Vitamin D may become a part of AITDs' treatment, especially in those with Vitamin D insufficiency. Further clinical and experimental studies are required to understand the effect of Vitamin D on AITD.

Transcatheter closure of patent ductus arteriosus in under 6 kg and premature infants.

BACKGROUND: Transcatheter closure of a patent ductus arteriosus (PDA) has always been considered risky for infants weighing <6 kg and preterms. We present our findings regarding transcatheter closures of PDA. METHODS: The inclusion criteria were a weight of <6 kg and the presence of PDA symptoms. The study subjects were divided into two groups: <6 kg and premature infants. RESULTS: A total of 69 infants were included. The mean ages and weights of the <6 kg and the preterms were 5.4 ± 2.7 months and 30.3 ± 19.9 days, and 4.6 ± 0.8 and 1.7 ± 0.3 kg, respectively. Type C PDAs were most frequently observed in the premature group, and type A was in <6 kg. Sixteen of the patients were premature infants, and 81.2% of them had an extremely low birth weight. All of the premature infants had comorbidities, and had been receiving respiratory support therapy. Transcatheter closure was successfully completed in 81.2% of the premature infants and 94.3% of the <6-kg infants. Major complications occurred in 4 patients (one death and three device embolizations). The patient's age was found to be the main risk factor. The most frequently used device was the Amplatzer duct occluder II in additional sizes (84.6%) in the preterms and the Amplatzer duct occluder I (34%) and II (34%) in the <6-kg group. CONCLUSION: The transcatheter closure of PDA is relatively safe and effective in preterms and in infants <6 kg. The selection of a suitable device based on the type of PDA is critical to the success of the procedure.