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)

     

Risk factors for the development of PTSD and depression among child and adolescent victims following a 7.4 magnitude earthquake

Objective. PTSD and major depression occur frequently following traumatic exposure, both as separate disorders and concurrently. Although much of Turkey is under threat of severe earthquakes, risk factors for developing psychiatric disorders among Turkish children have not yet been studied. The aim of the study was to examine risk factors for PTSD and depression develpoment in children. Method. A total of 160 survivors (102 girls and 58 boys) severely impacted by Turkey's 7.4-magnitude quake participated in a psychiatric interview 6–20 weeks after the disaster. The mean age was 14.43. Logistic regression was used to test effects of pre-disaster, disaster-related and post-disaster factors on diagnoses, yielding odds ratios (OR). Results. CAPS indicated that 96 (60%) had PTSD, and psychiatric interview found 49 (31%) with depression. Children diagnosed with PTSD were more likely to have witnessed death (OR=2.47) and experienced an extreme parental reaction (OR=3.45). Children with depression were more likely to be male (OR=4.48), have a higher trait anxiety score (OR=1.12 for every additional point), sustain injury (OR=4.29), and have lost a family member in the quake (OR=10.96). Focusing on the 96 children with PTSD, those with comorbid depression were more likely male, have a higher trait anxiety score, and have lost of family member. Conclusions. Mental health professionals should offer support to children witnessing death or losing a family member in a disaster. The ability of the family to remain calm and reassuring also may be a key factor in preventing PTSD.     

Design and <Emphasis Type="BoldItalic">In Vitro</Emphasis> Evaluation of Bispecific Complexes and Drug Conjugates of Anticancer Peptide,LyP-1 in Human Breast Cancer

Purpose

LyP-1, a nine-amino-acid tumor homing peptide, selectively binds to its cognate receptor, p32. Overexpression of p32 in certain tumors should allow use of LyP-1 as a targeting agent for the delivery of therapeutic or diagnostic agents. Peptide conjugates are developed for enhanced pre-targeting of MDA-MB-231 breast cancer cells with peptide-antibody bispecific complexes and targeting with multiple-drug/-fluorophore-conjugated nano-polymers.

Methods

LyP-1-anti-DTPA bispecific antibody complexes (LyP-1-bsAbCx) were generated by conjugation of anti-DTPA antibody and LyP-1. LyP-1–doxorubicin (Dox), Dox-DTPA-succinyl-polylysine (Dox-DSPL), Dox-DSPL-LyP-1, DTPA-Dox-poly glutamic acid (D-Dox-PGA) or DTPA-rhodamine conjugated polylysine (DSPL-RITC) were prepared. In vitro therapeutic efficacy and targeting by immunofluorescence in MDA-MB-231 breast cancer cells were assessed with Dox-LyP-1. Immunofluorescence visualization of cancer cells was evaluated after pretargeting with LyP-1-bsAbCx and targeting with DSPL-RITC.

Results

Cytotoxicity of Dox-LyP-1 conjugates was significantly greater than free doxorubicin (p?<?0.0001). For fluorescent-labeled LyP-1, internalization occurred in 30 min in tumor cells. Fluorescence intensity of two-step targeted cells showed that pretargeting with LyP-1-bsAbC, followed by targeting with DSPL-RITC was greater than non-pretargeted DSPL-RITC (p?<?0.05).

Conclusions

Peptide-conjugates are effective targeting agents for MDA-MB-231 breast cancer cells in culture. LyP-1-bsAbCx and Dox-LyP-1 conjugates may allow development of novel targeted cancer therapy and diagnosis.

     

Are cardiac Magnetic Resonance Imaging and Radionuclide Ventriculography Good Options Against Echocardiography for Evaluation of Anthracycline Induced Chronic Cardiotoxicity in Childhood Cancer Survivors?

Anthracyclines are widely used for the treatment of solid tumors in pediatric oncology. However, their uses may be limited by progressive chronic cardiotoxicity related to the cumulative dosage. The aims of this study are to compare diagnostic techniques and prepare an algorithm for diagnosis of anthracycline induced chronic cardiotoxicity. The patients were evaluated according to age, sex, time elapsed since the last dose of anthracycline treatment, presence of cardiovascular symptoms, follow-up duration, type of anthracycline, cumulative anthracycline dose, and concomitant mediastinal radiation therapy. Late subclinical cardiotoxicity was detected by history, physical examination, electrocardiography (ECG), Holter monitor, echocardiography (ECHO), radionuclide ventriculography (MUGA), and cardiac magnetic resonance imaging (MRI). Thirty-seven male and 19 female patients with a median age of 11.2 ± 4.6 (range, 3.5–22.0) years were included in the study. Patients were grouped according to cumulative anthracycline doses. Subclinical cardiac dysfunction was detected in 20 patients by at least one of ECHO, MRI or MUGA after anthracycline chemotherapy. We revealed that other than ECHO, MRI and MUGA have high clinical importance for evaluating subclinical late cardiac complications in children treated with anthracyclines.     

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aimFamilial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia.Materials and methodsAll patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively.ResultsAmong 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively).ConclusionOur findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.     

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it’s hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001.ConclusionAppendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.     

Urinary Neopterin Levels in Patients with Thyroid Cancer

Increased urinary neopterin concentrations have been described in many cancers. We aimed to evaluate the urinary neopterin levels in thyroid cancer. Sixty-nine patients with thyroid cancer, 76 patients with benign thyroid pathology and 33 healthy subjects were evaluated. First morning urine samples were collected from the patients and normal subjects for neopterin and creatinine measurement and stored at −80 °C until analysed. Neopterin levels were 149.3 (15.2–1,602.2) μmol/mol creatinine in the malignant group, 32 (5.2–275.6) μmol/mol creatinine in the benign group and 9.2 (2.7–78.7) μmol/mol creatinine in normal subjects (p ≤ 0.001). Urinary neopterin levels were significantly higher in patients with thyroid cancer than patients with benign thyroid pathologies and normal subjects. Also the patients with benign thyroid pathologies had a higher urinary neopterin level than the normal subjects. Malignant group was divided to two groups; patients with/without chronic thyroiditis (confirmed histologically). There were 22 (31.9 %) patients with and 47 (68.1 %) patients without chronic thyroiditis. Urinary levels of neopterin didn’t differ in both groups (168.6 (21.3–716.8) μmol/mol creatinine and 135.3 (15.2–1,602.2) μmol/mol creatinine respectively; p = 0.381). Urinary neopterin levels are high in thyroid cancer patients independently from the presence of chronic thyroiditis.     

Comparison of serological and clinical findings in Turkish patients with cystic echinococcosis

Summary Cystic echinococcosis (CE), caused by the cestode Echinococcus granulosus, is potentially dangerous for humans. The aim of this study was to examine serological and clinical findings regarding cysts localisation and individual responses in 54 patients with CE. The majority of patients in this study were females (63 %) and the average age was 46.3 years. Most of the patients lived in rural areas or kept a dog (46 %) for a long time. The most frequent symptoms were hypochondrial pain (48.9 %), epigastrial discomfort (27.7 %), vomiting (21.3 %), minor cough (12.8 %), urticaria (6.3 %), weakness (4.3 %), fever (2.1 %), side-or back-ache (4.3 %). However, 17 % of the patients showed no symptoms. In every case, the ultrasound (USG) and/or computer tomography (CT) investigations were positive. In most cases (53.2 % of the patients) a single cyst was found but 46.8 % of the patients had multiple cyst formations (from 2 to 9 cysts) located in the liver. Sporadic lung, splenetic, mesenterial, tibial and cerebral localisations were also found. The patients were individually treated with albendazol (10–15 mg/kg) five days prior and six months after the surgical treatment. Serum samples were investigated by the serological techniques: IHAT, ELISA and Western blot using hydatid fluid antigen. In the patient sera, the specific antibody levels were mostly increased after surgery. Different results were obtained only in two patients. In the first case, seroconversion was delayed. In the other case all ELISA results were negative, however, the Western blot analysis and surgery proved the presence of CE. The results suggest that the different antibody response of patients depends on the individual immune response. Multiple localization and various stages of CE cysts demonstrate the necessity of a complex approach for the confirmation of a correct diagnosis.     

Factors playing a role in the development of decreased bone mineral density in juvenile chronic arthritis

OBJECTIVE: The aims of this study were to evaluate bone mineral density (BMD) in patients with juvenile chronic arthritis (JCA), compare them with healthy controls, and assess the effects of disease activity and corticosteroid treatment on BMD. METHODS: Twenty-eight patients diagnosed with JCA and 45 healthy controls were included in this study. Disease activity was determined by clinical and laboratory evaluation, Articular Disease Severity Score (ADSS), and the Juvenile Arthritis Functional Assessment Report (JAFAR). Bone mineral density of the lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). RESULTS: Patients with JCA showed significant decreases in BMD compared with healthy controls. The JCA patients treated with corticosteroids showed significantly lower BMDs than the healthy control group. Age of the patients and age of onset were found to correlate with BMD. CONCLUSION: Our study showed that glucocorticoids were involved in the development of osteoporosis in JCA, with many other factors affecting bone mineralization. We could not demonstrate any relationship between BMD and disease activity, but the study data suggest that early onset disease is also an important factor in the development of osteoporosis in JCA.