Seasonal Variation in Sudden Cardiac Death: Insights from a Large United Kingdom Registry

Background Sudden cardiac death (SCD) is relatively common and may occur in apparently healthy individuals. The role of seasonal variation as a risk factor for SCD is poorly understood. The aim of this study was to investigate whether SCD exhibits a predilection for specific seasons. Methods We reviewed a database of 4751 cases of SCD (mean age 38 ± 17 years) referred to our center for cardiac pathology at St George’s University of London between 2000 and 2018. Clinical information was obtained from referring coroners who were asked to complete a detailed questionnaire. All cases underwent macroscopic and histological evaluation of the heart, by expert cardiac pathologists. Results SCD was more common during winter (26%) and rarer during summer (24%), p= 0.161. Significant seasonal variation was not observed among cases of sudden arrhythmic death syndrome (SADS, 2910 cases) in which the heart is structurally normal. In contrast, a significant difference in seasonal distribution among decedents exhibiting cardiac structural abnormalities at the post-mortem examination (n=1841) was observed. In this subgroup, SCDs occurred more frequently during winter (27 %) compared to summer (22%) (p=0.007). In cases diagnosed with a myocardial disease (n=1399), SCD was most common during the winter (27%) and least common during the summer (22%) (p=0.027). Conclusions While SADS occurs throughout the year with no seasonal variation, SCD due to structural heart disease appears to be more common during the winter. Bio-meteorological factors may be potential triggers of SCD in individuals with an underlying structural cardiac abnormality

CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a ‘pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

BACKGROUND: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS: In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P>0.001), vascular invasion (P=0.009), worse survival in univariate (P>0.001) and multivariable (P>0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P>0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P>0.001). CONCLUSION: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease

Stasis dermatitis-like leukaemic infiltration in a patient with myelodysplastic syndrome

We report a case of leukaemia cutis presenting as stasis dermatitis-like eruption in a patient with myelodysplastic syndrome progressing to acute myelogenic leukaemia. © 2008 The Author(s)

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

AIM: To assess human epidermal growth factor receptor- 2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH). METHODS: 120 cases of primary gastric carcinomas and 45 matched lymph node metastases from patients with full clinicopathological features were mounted onto multiple-punch and single-punch tissue microarrays, respectively, and examined for HER2 overexpression and gene amplification by IHC and CISH. RESULTS: Twenty-four tumors (20%) expressed HER2 immunohistochemically. An IHC score of ≥ 2+ was observed in 20 tumors (16.6%). HER2 amplification was detected by CISH in 19 tumors (15.8%) and in their matched lymph node metastases. A high concordance rate was found between HER2 positivity (as detected by IHC) and HER2 gene amplification (as detected by CISH), since 19 of the 20 IHC positive cases were amplified (95%). All amplified cases had 2+ or 3+ IHC results. Amplification was associated with intestinal phenotype (P < 0.05). No association with grading, staging or survival was found. CONCLUSION: In gastric cancer, HER2 amplification is the main mechanism for HER2 protein overexpression and is preserved in lymph node metastases. © 2012 Baishideng. All rights reserved

Development of two primary malignant melanomas after treatment with adalimumab: A case report and review of the possible link between biological therapy with TNF-α antagonists and melanocytic proliferation

Biologics, such as tumor necrosis factor α (TNF-α) antagonists, have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. There is growing evidence linking biological treatments with the occurrence of malignancies or reactivation of latent ones, including malignant melanoma. We report the case of a 75-year-old male patient who developed 2 primary malignant melanomas (MM) after treatment with adalimumab for rheumatoid arthritis. He was under adalimumab treatment for approximately 12 months before the diagnosis of MM on his right lower leg. After surgical removal and staging, no evidence of metastases was found. A few months later, a second MM developed on the patient's scalp. The short duration of treatment with adalimumab and the unclear temporal relationship cannot adequately support a probable link between this double MM occurrence and the adalimumab-induced immunosuppressive state. The result of a literature search regarding the possible association between anti-TNF drugs and melanocytic proliferation is provided. Copyright © 2010 S. Karger AG

Immnohistochemical expression of p53, MDM2 and p21(Waf1) oncoproteins in endometriomas but not adenomyosis

OBJECTIVE: p53, MDM2, and p21(Waf1) are oncoproteins that regulate the cell cycle. The purpose of this study was to examine the distribution of p53, MDM2 and p21(Waf1) oncoprotein expression in endometriomas and in adenomyosis. METHODS: Tissue samples from 25 women with pathologically confirmed endometriomas and 3 1 women with pathologically confirmed adenomyosis were analyzed. Expression of p53, MDM2, and p21(Waf1) oncoproteins was assessed by immunohistochemical nuclear staining. RESULTS: p53, MDM2, and p21(Waf1) expression were detected ill 20%, 60%, and 80% of endometrioma tissue samples, respectively. All endometrioma tissue samples expressing p53 also tested positive for both MDM2 and p21(Waf1). MDM2 expression was significantly higher ill the proliferative than ill the secretory phase of the cycle. In contrast, all 31 adenomyosis tissue samples were negative for p53, MDM2, and p21(Waf1) expression. CONCLUSION: The expression of p53, MDM2, and p21(Waf1) suggests a role for these oncoproteins in the regulation of endometrioma cell growth, but not ill adenomyosis. Copyright (c) 2005 by the Society for Gynecologic Investigation

Cutaneous involvement in angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma characterized by general lymphadenopathy, night sweats, fever, hepatosplenomegaly, polyclonal hypergammaglobulinemia, and cutaneous involvement. We present a rare case of AITL cutaneous involvement mimicking toxic erythema recurring with AITL relapse and suggesting a precursor of disease progression