Assessing the association between genetic and phenotypic features of dilated cardiomyopathy and outcome in patients with coronary artery disease.

AIMS: To examine the relevance of genetic and cardiovascular magnetic resonance (CMR) features of dilated cardiomyopathy (DCM) in individuals with coronary artery disease (CAD). METHODS AND RESULTS: This study includes two cohorts. First, individuals with CAD recruited into the UK Biobank (UKB) were evaluated. Second, patients with CAD referred to a tertiary centre for evaluation with late gadolinium enhancement (LGE)-CMR were recruited (London cohort); patients underwent genetic sequencing as part of the research protocol and long-term follow-up. From 31 154 individuals with CAD recruited to UKB, rare pathogenic variants in DCM genes were associated with increased risk of death or major adverse cardiac events (hazard ratio 1.57, 95% confidence interval [CI] 1.22-2.01, p < 0.001). Of 1619 individuals with CAD included from the UKB CMR substudy, participants with a rare variant in a DCM-associated gene had lower left ventricular ejection fraction (LVEF) compared to genotype negative individuals (mean 47 ± 10% vs. 57 ± 8%, p < 0.001). Of 453 patients in the London cohort, 63 (14%) had non-infarct pattern LGE (NI-LGE) on CMR. Patients with NI-LGE had lower LVEF (mean 38 ± 18% vs. 48 ± 16%, p < 0.001) compared to patients without NI-LGE, with no significant difference in the burden of rare protein altering variants in DCM-associated genes between groups (9.5% vs. 6.7%, odds ratio 1.5, 95% CI 0.4-4.3, p = 0.4). NI-LGE was not independently associated with adverse clinical outcomes. CONCLUSION: Rare pathogenic variants in DCM-associated genes impact left ventricular remodelling and outcomes in stable CAD. NI-LGE is associated with adverse remodelling but is not an independent predictor of outcome and had no rare genetic basis in our study.

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.

AIMS: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). METHODS AND RESULTS: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months. CONCLUSION: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

Is skipped nodal metastasis a phenomenon of cutaneous melanoma?

BACKGROUND AND METHODS: Skipped nodal metastasis (SNM) is a recognized phenomenon of visceral cancers when metastases bypass the regional basin and skip to a distant nodal basin without evidence of distant metastases. Its occurrence is undocumented in cutaneous melanoma patients but of potential prognostic significance. We therefore assessed the frequency of SNM in a large series of patients with limb melanomas. PATIENTS AND METHODS: We studied melanoma patients attending a tertiary oncology hospital in northwest England using two approaches. First, we systematically searched medical records of an unselected patient sample treated 2002-2015, and second, we studied lymphoscintigrams of all patients with limb melanoma who underwent sentinel node biopsy 2008-2019. RESULTS: Of 672 melanoma patients whose clinical records were examined, 16 had regional nodal metastases without apparent visceral spread and one appeared to have SNM but further scans were uncovered that showed concurrent pulmonary metastases. Of 667 limb melanoma patients with lymphoscintigrams, 7 showed dual lymphatic drainage patterns to distal as well as regional nodal basins, but none had micro-metastases solely in the distant basin. CONCLUSION: Occurrence of SNM in cutaneous melanoma is highly unlikely.

Cytotoxicity of silver dressings on diabetic fibroblasts.

A large number of silver-based dressings are commonly used in the management of chronic wounds that are at risk of infection, including diabetic foot ulcers. However, there are still controversies regarding the toxicity of silver dressings on wound healing. The purpose of this study was to objectively test the cytotoxicity of silver dressings on human diabetic fibroblasts. Human diabetic fibroblasts were obtained from the foot skin of four diabetic foot ulcer patients and cultured. The effect of five silver-containing dressing products (Aquacel Ag, Acticoat*Absorbent, Medifoam Ag, Biatain Ag and PolyMem Ag) and their comparable silver-free dressing products on morphology, proliferation and collagen synthesis of the cultured human diabetic fibroblasts were compared in vitro. In addition, extracts of each dressing were tested in order to examine the effect of other chemical components found in the dressings on cytotoxicity. The diabetic fibroblasts cultured with each silver-free dressing adopted the typical dendritic and fusiform shape. On the other hand, the diabetic fibroblasts did not adopt this typical morphology when treated with the different silver dressings. All silver dressings tested in the study reduced the viability of the diabetic fibroblasts and collagen synthesis by 54-70 and 48-68%, respectively, when compared to silver-free dressings. Silver dressings significantly changed the cell morphology and decreased cell proliferation and collagen synthesis of diabetic fibroblasts. Therefore, silver dressings should be used with caution when treating diabetic wounds.

Facial dermis grafts after removal of basal cell carcinomas.

Selecting a proper reconstruction method is the key to success in skin cancer management, especially for lesions involving the face. Using a skin graft is usually straightforward when covering a skin defect; however, major concerns in skin grafting include a poor color match in the recipient-site and donor-site morbidity. To overcome these limitations, the authors have developed a dermis graft, which utilizes a de-epithelialized split-thickness skin graft method. The purpose of this retrospective study was to report reliability of dermis grafts after removal of basal cell carcinomas (BCCs) on the face by presenting our clinical experience with them. This study included 38 patients who were treated for facial defects created by resection of BCCs. The locations of the defects were as follows: nose (n = 17), orbital area (n = 14), cheek (n = 4), temple area (n = 2), and forehead (n = 1). The defects ranged in size from 3.3 to 6.5 cm. Functional and cosmetic outcomes, postoperative complications, and patient satisfaction were assessed. The patients were followed up for 12 to 36 months. The entire dermis graft re-epithelialized after grafting within 17 to 27 days. Most of the patients had satisfactory results in both functional and cosmetic matters with high-quality skin characteristics. There were no significant complications and no recurrences were observed during the follow-up period. Patient satisfaction with the dermis graft was also excellent. The dermis graft may be used reliably for covering defects after removal of BCCs on the face.

Fingertip reconstruction using free toe tissue transfer without venous anastomosis.

BACKGROUND: This study was designed to introduce the feasibility of toe tissue transfer without venous outflow for fingertip reconstruction. METHODS: Five cases of fingertip defects were treated successfully with this method. Four cases were traumatic fingertip defects, and one case was a hook-nail deformity. The lateral pulp of a great toe or medioinferior portion of a second toe was used as the donor site. An arterial pedicle was dissected only within the digit and anastomosis was performed within 2 cm around the defect margin. The digital nerve was repaired simultaneously. No additional dissection of the dorsal or volar pulp vein was performed in either the donor or recipient sites. Other surgical procedures were performed following conventional techniques. Postoperative venous congestion was monitored with pulp temperature, color, and degree of tissue oxygen saturation. Venous congestion was decompressed with a needle-puncture method intermittently, but did not require continuous external bleeding for salvage. RESULTS: Venous congestion was observed in all the flaps, but improved within 3 or 4 days postoperatively. The flap size was from 1.5×1.5 cm(2) to 2.0×3.0 cm(2). The mean surgical time was 2 hours and 20 minutes. A needle puncture was carried out every 2 hours during the first postoperative day, and then every 4 hours thereafter. The amount of blood loss during each puncture procedure was less than 0.2 mL. In the long-term follow-up, no flap atrophy was observed. CONCLUSIONS: When used properly, the free toe tissue transfer without venous anastomosis method can be a treatment option for small defects on the fingertip area.