Association between reverse electrical remodeling and cardiac fibrosis markers in patients with cardiac resynchronization therapy.

OBJECTIVE: Cardiac resynchronization therapy (CRT) induces structural and electrical reverse remodeling of the failing heart. However, the association between native QRS narrowing and cardiac fibrosis markers has not been investigated in patients with an implanted CRT device. METHODS: A total of 41 symptomatic patients diagnosed with systolic heart failure who underwent CRT implantation were included in this study. Electrocardiogram findings and cardiac fibrosis marker levels [galectin-3, growth-differentiation factor-15 (GDF-15) and procollagen III N-terminal propeptide (P3TD)] were collected before and 12 months after initiation of biventricular pacing. Reverse electrical remodeling was defined as a decrease in 12-month intrinsic QRS (iQRS) duration by ≥20 milliseconds after CRT implantation. RESULTS: The median QRS duration decreased from 155 milliseconds (interquartile range [IQR]: 142-178 milliseconds) before CRT to 142 milliseconds (IQR: 130-161 milliseconds) (p=0.001) after 12 months of CRT. According to the predefined criteria, electrical remodeling was detected in 16 (39.0%) patients. The median galectin-3, GDF-15, and P3TD levels were significantly decreased after CRT implantation in patients with electrical remodeling [27.65 ng/mL (IQR: 24.4-35.2 ng/mL) vs 23.00 ng/mL (IQR: 16.0-36.7 ng/mL), p=0.017; 3104 pg/mL (IQR: 2923-4825 pg/mL) vs 2276 pg/mL (IQR: 1294-3209 pg/mL), p=0.002; 0.43 ng/mL (IQR: 0.23-0.64) vs 0.15 ng/mL (IQR: 0.04-0.29 ng/mL), p=0.034, respectively]. The galectin-3, GDF-15, and P3TD levels were not significantly changed in patients without electrical remodeling [26.80 ng/mL (IQR: 23.9-31.5 ng/mL) vs 28.80 ng/mL (IQR: 23.0-34.8 ng/mL), p=0.211; 4221 pg/mL (IQR: 2709-4995 pg/mL) vs 3035 pg/mL (IQR: 2038-4872 pg/mL), p=0.143; and 0.34 ng/mL (IQR: 0.11-0.68 ng/mL) vs 0.21 ng/mL (IQR: 0.09-0.37 ng/mL), p=0.112, respectively]. CONCLUSION: The results from the small sample used in this study indicated that electrical reverse remodeling after CRT was associated with a decrease in cardiac fibrosis.

Evaluating the effects of cardiac resynchronization therapy on pathophysiological pathways of heart failure using surrogate biomarkers.

BACKGROUND: Several studies have investigated the effects of cardiac resynchronization therapy (CRT) on heart failure (HF), but none have evaluated the pathophysiological pathways involved in a single group of patients. Therefore, this study aims to assess the long-term effects of CRT on six different patho-physiological pathways involved in the process of HF by the use of surrogate biomarkers. METHODS: In a group 44 patients with HF, six groups of biomarkers were measured, both at baseline and 1 year after CRT implantation: inflammation (interleukin [IL]-4, IL-6, tumor necrosis fac-tor [TNF]-a, high sensitive C-reactive protein [hsCRP]); oxidative stress (myeloperoxidase [MPO], oxidized low-density lipoprotein [oxLDL], uric acid); extracellular matrix (ECM) remodeling (matrix metalloproteinase [MMP]-2 and -9, galectin-3, procollagen III N-terminal propeptide [prokol-3NT]); neurohormonal pathways (endothelin-1, chromogranin-A); myocyte injury (troponin T, creatine kinase MB fraction [CK-MB]), myocyte stress (B-type natriuretic peptide [BNP]). CRT responders were de-fined as patients with ≥ 15% reduction in left ventricular end-systolic volume at 12 months post-CRT. RESULTS: At 1-year follow-up, 72.7% (n = 32) of the patients were categorized as CRT responders. In these patients, the levels of IL-6, MPO, oxLDL, MMP-2, galectin-3, troponin T, and BNP were significantly reduced as compared to baseline values. While the biomarkers for myocyte stress (effect size = 0.357; p = 0.001), ECM remodeling (effect size = 0.343; p = 0.015) and oxidative stress (effect size = 0.247; p = 0.039) showed a significant change in the CRT responders during follow-up, the biomarkers for other pathophysiological pathways did not show a significant alteration. CONCLUSIONS: In the present study, a significant reduction was only observed in the biomarkers of myo-cardial stress, ECM remodeling, and oxidative stress among all the CRT responder subjects. (Cardiol J 2018; 25, 1: 42-51).

Effect of reduction mammoplasty on the pulmonary function tests.

INTRODUCTION: Bilateral breast reduction surgery is the surgical treatment of bilateral breast hypertrophy. This is one of the most common breast surgery requested by women, and performed by plastic surgeons. The reasons that patients want this surgery are to re-size sagging breasts aesthetically, and to get rid of somatic symptoms such as shoulder, chest, back, and neck pain. We believe that the objective positive effects of breast reduction surgery exist beside aesthetic. In our study, our aim is to elicit positive effects of surgery on lungs, if there are, by making pulmonary function test and carbon monoxide diffusion test before surgery and after 6 months of surgery. MATERIALS AND METHODS: Thirty patients agreed to participate in the study. Study is completed with 19 patients. Pulmonary function test and carbon monoxide diffusion test were made to all patients in preoperative and 6 months of postoperative period. Lung roentgenogram of all patients was performed and height, weight, body mass index were measured. Saturation level was measured. RESULT: There was a meaningful increase in FEV1 and FVC values in the postoperative period in comparison with pulmonary function test performed in preoperative period. DLCO in postoperative period decreased meaningfully as compared to the preoperative period. CONCLUSIONS: Breast reduction surgery seems to have positive effects on pulmonary function test values and relaxes patients clinically. Patients with big breasts should be evaluated from this perspective if they apply chest diseases clinic with shortness of breath.

Facial Actinomycosis Mimicking a Cutaneous Tumor.

Actinomycosis is a chronic granulomatous infection that commonly occurs in the cervicofacial region. Although Actinomcyes is an element of the normal oral flora, infections of the facial skin are very rare because of the entirely endogenous habitation of the organism. The authors report a case of facial actinomycosis, which mimicked a cutaneous tumor both clinically and surgically in a 44-year-old woman with chronic renal failure and Hepatitis C viral infection. The majority of cases can be treated with long-term antibiotics. However, a treatment-resistant abscess, a fistula, or postsurgical excision of the mass formation that are infected can be treated with antibiotics as soon as possible, and recurrence of infection is prevented. The treatment should consist of conservative surgery to obtain a firm histological diagnosis and to drain any collections.

Metachromatic leukodystrophy: Biochemical characterization of two (p.307Glu→Lys, p.318Trp→Cys) arylsulfatase A mutations.

Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by Arylsulfatase A (ASA) deficiency. The hallmark of the disease is central and peripheral neurodegeneration. More than 200 mutations have been identified in ARSA gene so far. Some of these mutations were characterized. The aim of this study is to reinforce genotype-phenotype correlation and to understand the effect of mutations on the enzyme by biochemical characterization. Two missense mutations (c.919G→A, p.307Glu→Lys and c.954G→T, p.318Trp→Cys in exon 5) were constructed on WT-ASA cDNA and were confirmed by DNA sequence analysis. Plasmid DNA carrying mutant or normal ASA cDNA was transferred to Chinese Hamster Ovary (CHO) cells through transient transfection. ASA protein was produced by CHO cells. Hexosaminidase beta-subunit gene was cotransfected into the CHO cells as a control gene of transfection efficiency. 48 hours after transfection, cells were collected and homogenized. ASA and hexosaminidase activities were measured in supernatant. ASA enzyme activity is decreased 100% according to the control by the effect of both mutations. The mutations are located in the higly conserved region of the protein. In this study, we showed that both mutations result in null ASA activity in CHO cells making the protein nonfunctional. We confirmed that p.307Glu→Lys and p.318Trp→Cys mutations cause late infantile form of MLD disease.

Effect of Concentrated Growth Factor on Survival of Diced Cartilage Graft.

BACKGROUND: Diced cartilage grafts are important in rhinoplasty for raising the dorsum and eliminating dorsal irregularities. The most common problems with the use of diced cartilage are wrapping and cartilage resorption. OBJECTIVES: To histopathologically investigate and compare the viability of diced cartilage grafts wrapped with concentrated growth factor, fascia and fenestrated fascia, or blood glue. METHODS: Cartilage grafts were harvested from the ears of 10 New Zealand White rabbits and diced into 0.5 to 1 mm3 pieces. The grafts were divided into five groups for comparison: (1) bare diced cartilage; (2) diced cartilage wrapped with fascia; (3) diced cartilage wrapped with fenestrated fascia; (4) diced cartilage wrapped with concentrated growth factor (CGF); and (5) diced cartilage wrapped with blood glue. Each of the five grafts was autologously implanted into a subcutaneous pocket in the back of each rabbit. Three months later, the rabbits were sacrificed and the implants were harvested and examined histopathologically. RESULTS: Nucleus loss, calcification, inflammation, and giant cell formation differed significantly between the CGF group and both fascia groups. Chondrocyte proliferation was the highest in the CGF group. Nucleus loss rates were similar between the fascia and fenestrated fascia groups. CONCLUSIONS: Our findings suggest that CGF improves the viability of diced cartilage grafts, while fascia hampers it. Punching holes in the fascia does not improve diced cartilage graft viability and neither does blood glue wrapping.

Effectiveness of Palatal Mucosa Graft in Surgical Treatment of Sub-Glottic Stenosis.

OBJECTIVES: Mucosal free grafts may be successfully applied in many surgical interventions. This study aims at investigating the feasibility of palatal mucosa graft in sub-glottic field in an animal model. METHODS: This randomized prospective controlled study was conducted with an animal model. Sub-glottic inflammation was created in 15 adult rabbits in each group and sub-glottic stenosis surgery was applied thereafter. The rabbits in group 1 (control group) underwent segmental resection, partial cricoidectomy, and trachea-thyroid cartilage anastomosis; the rabbits in group 2 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free buccal mucosa graft; and the rabbits in group 3 underwent segmental resection, cricoplasty, and crico-tracheal anastomosis using free palatal mucosa graft. Re-stenosis was evaluated after 42 days. RESULTS: The percentages of stenosis were 27%±20%, 40%±20%, and 34%±23% for group 1, 2, and 3, respectively and the difference was not statistically significant (P=0.29). Intensive and tight fibrosis was observed in 2 rabbits (13%) in group 1, in 5 rabbits (33%) in group 2, and in 3 rabbits (20%) in group 3. There was not a statistically significant difference between groups (P=0.41). Excessive inflammation was observed in 3 rabbits (20%) in group 1, in 7 rabbits (47%) in group 2, and 3 rabbits (20%) in group 3. There was no a statistically significant difference between groups although inflammation rate was higher in the rabbits which underwent buccal mucosa graft (P=0.18). CONCLUSION: The surgical treatments applied with free mucosa graft reduced anastomosis tension through enabling anastomosis to the distal of cricoid instead of thyroid cartilage. Free palatal mucosa grafts may be used in sub-glottic field, one of the most challenging fields of trachea surgery, due to ease of application and rapid vascularization.

Survival of Minced Cartilage Grafts with Comparison Surgicel(®) Original and Fibrillar.

BACKGROUND: Cartilage grafts are commonly used in nasal surgery for structural and/or esthetic purposes. The viability of cartilage grafts has been investigated in many forms since the use of cartilage grafts in surgical procedures. OBJECTIVES: The objective of this study was to investigate the viability of minced cartilage grafts and whether there is a difference between grafts wrapped in Surgicel(®) Original and Surgicel Fibrillar. METHODS: A total of ten New Zealand rabbits were used for the study. Cartilage grafts were harvested from one side ear. Four groups were formed. Group 1: minced cartilage graft wrapped in Surgicel Fibrillar; Group 2: minced cartilage graft wrapped in Surgicel Original; Group 3: bare minced cartilage graft; and Group 4: bare diced cartilage graft. Four small subcutaneous pockets were made in the backs of the rabbits, and the grafts were placed in these pockets. All of the rabbits were sacrificed at the end of 3 months, and the samples were collected. The sections were stained with hematoxylin and eosin (H&E), toluidin blue, safranin-O, masson trichrome, and glial fibrillary acidic protein immunohistochemical. All specimens were assessed histopathologically under a light microscope. RESULTS: There was no statistically significant difference between the Surgicel Fibrillar and Surgicel Original groups with respect to any of the parameters. Bone formation, calcification, inflammation, fibrosis, and basophilia were similar in all groups, with no significant difference among them. In the Surgicel Fibrillar and Surgicel Original groups, a heavy chondrocyte nucleus loss accompanied by a minimal peripheral proliferation was observed. CONCLUSIONS: The viability of bare minced cartilage grafts was found to be similar to that of bare diced cartilage in this study. Minced cartilage grafts can be used in the correction of minor dorsal defects and irregularities in persons with thin nasal skins, especially in primary and revision rhinoplasty. Although there is no statistically significant difference between the Surgicel Fibrillary and Surgicel Original groups, we think that, if it is necessary to use oxidized regenerated cellulose, it should be in the fibrillar form. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Vitamin D levels predict the response to cardiac resynchronization therapy in patients with systolic heart failure.

OBJECTIVE: The aim of this study was to examine the relationship between vitamin D levels in patients with heart failure (HF) and response to cardiac resynchronization therapy (CRT). METHODS: We studied 57 patients (mean age: 60.47±13.09 years) with New York Heart Association Class II or III heart failure, QRS duration ?120 milliseconds, and ejection fraction <35% (mean: 27.1±4.4%) who underwent CRT. All patients were taking optimal medical treatment for HF. Patients were classified as CRT responders if they had >15% decrease in left ventricular end-systolic volume at 6 months compared with baseline measurements. Vitamin D levels were evaluated before CRT implantation with ELISA. RESULTS: Of the 57 patients, 34 patients (59.6%) were classified as responders and 23 patients (40.4%) were classified as non-responders. Baseline features, laboratory findings, and echocardiographic characteristics were nearly the same in both groups. High vitamin D level was detected in responder group compared to non-responder group (26.17±7.5 ng/mL vs 21.15±5.9 ng/mL; p=0.009). Age, hypertension, diabetes mellitus, ischemic cardiomyopathy, QRS morphology and duration, and levels of B-type natriuretic peptide (BNP) and vitamin D were associated with CRT response in our study population. In multivariate regression analysis, preimplantation QRS duration, and BNP and vitamin D levels remained independent predictors (QRS duration Odds ratio [OR]: 1.047, CI: 1.019-1.417, p=0.006; BNP OR: 0.997, 95% CI: 0.994-0.999, p=0.029; vitamin D OR: 1.121, 95% CI: 1.011-1.242, p=0.030). CONCLUSION: In the present study, preimplantation level of vitamin D was found to be predictor of response to CRT.

The Use of the PlasmaBlade and Acellular Dermal Matrix in Rhinophyma Surgery: A Case Report.

BACKGROUND: Rhinophyma is a rare, disfiguring disease characterized by a slow progressive overgrowth of the soft tissue of the nose associated with end-stage severe acne rosacea. OBJECTIVE: We present a case of severe rhinophyma treated successfully using PlasmaBlade and acellular dermal matrix with split-thickness skin graft. METHODS: This procedure combines deep excision with PlasmaBlade followed by coverage with an acellular dermal matrix for dermal substitution and split-thickness skin graft. RESULTS: Functional and aesthetic results were satisfactory. CONCLUSION: We offer a new approach to surgical treatment of rhinophyma. Total excision of phymatous tissue and single session replacement of epidermal-dermal components is an effective treatment for patients with severe rhinophyma, resulting in satisfactory functional and aesthetic outcome. This combined treatment modality prevents the recurrence of rhinophyma. It should be considered an appropriate alternative in cases of severe rhinophyma.

Multidetector computed tomography angiography to evaluate the subscapular arterial tree.

OBJECTIVE: The subscapular artery has an important place in reconstructive surgery. The major pedicles of several different flaps used widely in reconstructive surgery take their roots from this arterial tree. This study aimed to provide anatomical data relating to these vessels through the use of multidetector computed tomography angiography (MDCTA) and to evaluate the clinical utility of MDCTA tool prior to surgery. METHODS AND MATERIALS: A radiological evaluation using a MDCTA was made of the bilateral subscapular arteries and branches measuring >0.5 mm in diameter that could be sufficiently identified as vascular structures in 92 patients (44 men and 48 women) with pneumonia, pleural effusion, lung masses, or nodules for which a thoracic MDCTA was requested for the purpose of diagnosis. RESULTS: The mean diameter of the subscapular artery origin was 3.86 ± 0.60 mm on the left and 3.93 ± 0.62 mm on the right. The mean diameter of the circumflex scapular artery origin was 2.41 ± 0.37 mm on the left and 2.44 ± 0.39 mm on the right. The mean diameter of the thoracodorsal artery origin was 2.29 ± 0.27 mm on the left and 2.31 ± 0.29 mm on the right. Mean length of the circumflex scapular artery was 46.34 ± 9.41 mm on the left and 46.10 ± 8.81 mm on the right. Mean length of the latissimus dorsi branch of the thoracodorsal artery from the origin of the subscapular artery was 110.11 ± 17.42 mm on the left and 112.21 ± 14.60 mm on the right. Mean length of the serratus anterior branch was 124.25 ± 19.00 mm on the left and 120.84 ± 15.67 mm on the right. No differences were detected between the left and right sides or between sexes. Doubled circumflex scapular arteries were found in 4.3% of patients, and the circumflex scapular artery branched directly off the axillary artery in 3.2% of patients. CONCLUSION: This study showed that MDCTA is a highly valuable, non-invasive imaging tool for studying vascular anatomy and detecting variations in vascular structure during preoperative planning, thus enhancing surgical safety.

New insights into the mechanisms of diastolic dysfunction in patients with type 2 diabetes.

BACKGROUND: Little is known about the role of advanced glycation end products (AGEs) and their receptor (RAGE) in diabetic cardiovascular complications. Therefore, we aimed to evaluate the association of serum soluble RAGE (sRAGE) levels and left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes. METHODS: Our study consisted of 40 patients with type 2 diabetes and 40 age- and sex-matched healthy control group. Subjects with age ≥ 50 years old and any cardiovascular risk factors or conditions were excluded from the study. Serum sRAGE levels determined by enzyme-linked immunosorbent assay and LV diastolic dysfunction were evaluated according to current American Society of Echocardiography guidelines. RESULTS: Baseline characteristics were similar between groups except body mass index, waist-hip ratio, and fasting glucose levels. Serum sRAGE level was significantly lower in diabetic group compared with control group (676 ± 128 vs. 1044 ± 344, p < 0.05). Diastolic dysfunction was observed in 50% of diabetic patients (40% grade I and 10% grade II). Correlation analysis showed that serum sRAGE was negatively correlated with duration of diabetes, septal E'/A', lateral E'/A', and average E/E'. In multivariate regression analysis, serum sRAGE level was strongly associated with diastolic dysfunction in patients with type 2 diabetes. CONCLUSION: Our study showed that serum sRAGE level was significantly lower in type 2 diabetic patients aged < 50 years old. Also, sRAGE has negative correlation with the duration of diabetes and it was significantly associated with the presence of diastolic dysfunction in type 2 diabetes.

Preventing negative effects of smoking on microarterial anastomosis.

Although microsurgery has rapid expanded, problems related to microarterial anastomosis continue. Cigarette smoking is one of the major risks for anastomosis by increasing platelet adhesion, and its effects on endothelial cells. Aim of this article is to study the negative effects of cigarettes on microarterial anastomosis line, and to investigate the protective effects of recombinant human erythropoietin (rHuEPO).Ninety-six Sprague-Dawley male rats were divided into 3 groups: group 1 was the control. Rats in groups 2 and 3 were exposed to cigarette smoke starting 21 days prior to surgery for 3 times a day. In group 3, additional 150 IU/kg rHuEPO was given via subcutaneously every 48 hours after microvascular anastomosis, femoral arterial samples, and blood samples were taken for assessment at 1st, 3rd, 5th, and 7th day. Intimae/media ratios were calculated for morphologic analyses.On morphologic analysis of femoral arteries there were statistically significant differences for all 3 groups at 1st, 3rd, 5th, and 7th days (P < 0, 05). The group that made differences was group 2, according to one-way analysis of variance within 3 groups in all days.Smoking decreases endothelial cells healing and causes more thromboses. rHuEPO can prevent these negative effects of smoking.

Effects of isoflurane and sevoflurane on the survival of skin flaps in rats.

The effects of inhalational anaesthetic agents on survival of flaps are not well known. We investigated the effect of isoflurane and sevoflurane anaesthesia on survival of flaps using a caudally-based McFarlane skin flap in 20 male Wistar rats. Sevoflurane 1 minimum alveolar concentration (MAC) and isoflurane (1 MAC) in oxygen mixture was given to the animals. A 4 x10 cm caudally-based standard McFarlane flap was raised. There were no differences in any haemodynamic values or blood gases between the sevoflurane group and the isoflurane group. Skin flaps were assessed on the seventh day. The isoflurane group had a significantly smaller area of skin flap necrosis and an increased area of flap surviving than the sevoflurane group. We conclude that survival is significantly improved when isoflurane is used as the inhalational anaesthetic rather than sevoflurane.