Acute Hemorrhagic Edema of Infancy: A Troubling Cutaneous Presentation with a Self‐Limiting Course

Acute hemorrhagic edema of infancy (AHEI) is an unusual form of leukocytoclastic vasculitis with dramatic distinguishing skin lesions that occurs in infants ages 4 to 24 months old. The disease presents with skin eruptions that usually start with large (1–5 cm), symmetrically distributed, hemorrhagic lesions in a characteristic cockade pattern. The lesions are typically located on the lower extremities, face (in particular the ears, cheeks, and eyelids), and gluteal area. Fever may accompany skin eruptions. Clinical presentation at onset requires clinical and laboratory examination to distinguish it from more serious diseases and other vasculitis. The main differential diagnosis of AHEI is Henoch‐Schönlein purpura. AHEI is generally a self‐limiting disease, so a conservative approach should be considered. Topical or systemic corticosteroid therapy has been reported to be beneficial, as well as antihistamines and dapsone, although AHEI usually resolves completely with or without treatment. We report two cases of AHEI and an update of the literature.     

Expression of proteins involved in DNA damage response in familial and sporadic breast cancer patients

Understanding the expression of proteins involved in DNA damage response could improve knowledge of the pathways that contribute to familial and sporadic breast cancer (BC). We aimed to assess the different roles of BRCA1, poly(ADP‐ribose) polymerase‐1 (PARP1), BRCT‐repeat inhibitor of hTERT expression (BRIT1) and novel SWItch 5 (SWI5) expression in 130 sporadic and 73 familial BC samples, by immunohistochemistry. In the sporadic group, negative nuclear BRCA1 (nBRCA1) expression was associated with positive PgR (p = 0.037). Negative association was found between nBRCA1 expression and HER2 (p = 0.001). In the familial group, nBRCA1 expression was associated with ER (p = 0.002). Reduced nBRCA1 expression was associated with higher histological grade and positive Ki67 both in sporadic (p = 0.0010, p = 0.047) and familial groups (p < 0.001, p = 0.001). Nuclear PARP1 (nPARP1) expression was associated with histological grade (p = 0.035) and positive PgR (p = 0.047) in sporadic cases. High cytoplasmic and low nuclear BRIT1 (cBRIT1 and nBRIT1) expression were associated with high histological grade in the familial group (p = 0.013, p = 0.025). Various statistical associations between the protein expressions were observed in the sporadic group, while in familial group only few associations were found. Univariate analyses showed that nPARP1 expression is able to discriminate between sporadic and familial tumors (OR 2.80, p = 0.002). Multivariate analyses proved that its overexpression is an independent factor associated with a high risk of sporadic tumor (OR 2.96, p = 0.017). Our findings indicate that nPARP1 expression is an independent factor for sporadic BCs and PARP1 inhibitors could be a promising therapy for different phenotypes.     

Imaging in bone sarcomas. The chemotherapist's point of view

The role of imaging in planning oncologic treatment and follow-up of patients with bone sarcomas is discussed in the present article. Tumor staging and radiographic assessment of response to chemotherapy in bone sarcomas may be of difficult interpretation. In particular, the use of the criterion of tumor shrinkage to measure response to chemotherapy is not always applicable in bone tumors where higher calcification rather than reduction in size is frequently observed. New techniques such as (18)F-FDG PET/CT, dynamic contrast-enhanced computed tomography or magnetic resonance are now available allowing a more accurate staging of patients and adding information for the evaluation of tumor response. Innovative approaches aiming to evaluate vascular and metabolic response rather than mono- or bi-dimensional changes may be more informative and require further investigations.     

Prophylaxis of central venous catheter-related thrombosis with minidose warfarin: analysis of its use in 427 cancer patients

BACKGROUND: In the past few years, several studies have been performed to evaluate thrombosis prophylaxis with warfarin in cancer patients with central venous catheters (CVC), but the analysis of these studies does not allow firm conclusions to be drawn. PATIENTS AND METHODS: Four hundred and twenty-seven cancer patients were evaluated. Each received warfarin at a dose of 1 mg/daily as prophylaxis, starting the day after CVC positioning until its removal. RESULTS: The catheters were monitored for a mean of 168 days (range 22-706). There were 9 thrombotic events (1.8%). Overall, International Normalised Ratio (INR) elevation occurred in 55 (12.8%) patients. Bleeding was observed in 15 (3.5%) patients, 10 of whom had elevated INR levels. Of these, all were treated with continuous-infusion 5-Fluorouracil (5-FU)-based regimens. CONCLUSION: Minidose warfarin can protect from clinical thrombosis, but can induce an alteration in INR values and/or haemorrhagic symptoms in patients being treated with 5-FU-based regimens.     

A dedicated neural mechanism for vowel selection: a case of relative vowel deficit sparing the number lexicon

We report the case of an Italian speaker (GBC), with classical Wernicke's aphasia following a vascular lesion in the posterior middle temporal region. GBC exhibited a selective deficit in spoken language production affecting vowels more than consonants. In reading from a newspaper, GBC substituted vowels for other vowels from the Italian inventory at a rate of 7/1 compared to consonants. No effects of frequency or grammatical class were found. Vowel errors could also not be accounted for by morphological or known phonological processes. Production of number words, in contrast, was free from phonological errors. While GBC has intact representations of Italian vowels and consonants, his data argue for a separate selection mechanism for vowels that is dissociable from that used for consonants. This case provides neuropsychological evidence for models of word production that distinguish between the abstract phonological properties of a word (e.g., sequencing of phonemic slots, or "CV skeleton") and a separate representation for the specific sounds (melody).     

Sorafenib in hepatocellular carcinoma: prospective study on adverse events, quality of life, and related feasibility under daily conditions

The aim of this study was to investigate expression of CD147 and MMP-9 in triple-negative breast cancer (TNBC) so as to determine whether these two proteins may be correlated with poor prognosis of TNBC patients. We examined the expression levels of the CD147 and MMP-9 in 127 patients with TNBC and 30 patients with mammary gland fibroma using immunohistochemical staining before any treatments. Furthermore, we analyzed the correlation between the expression of these two proteins and various clinicopathologic factors including survival status of patients with TNBC. Positive stain of CD147 and MMP-9 was observed in all samples of TNBC. A statistically positive correlation was observed between the expression levels of CD147 and MMP-9 in TNBC tissues. The incidences of high expression were 48.0 % for CD147 and 53.5 % for MMP-9 in 127 TNBC tissues, respectively. High expression of either CD147 or MMP-9 was significantly correlated with clinical feature and shorter progression-free survival (PFS) (P_CD147 = 0.039; P_MMP-9 = 0.017) and overall survival (OS) (P_CD147 = 0.037; P_MMP-9 = 0.023). The expression levels of CD147 and MMP-9 are positively correlated with invasion, metastasis and shorter PFS/OS of TNBC. Patients with high expression of CD147 and MMP-9 had poor prognosis than TNBC patients with low expression.     

Gene expression deregulation by <Emphasis Type="Italic">KRAS</Emphasis> G12D and G12V in a <Emphasis Type="Italic">BRAF</Emphasis> V600E context

Background  

KRAS and BRAF mutations appear of relevance in the genesis and progression of several solid tumor types but the co-occurrence and interaction of these mutations have not yet been fully elucidated. Using a microsatellite stable (MSS) colorectal cancer (CRC) cell line (Colo741) having mutated BRAF and KRAS ^WT , we also aimed to investigate the KRAS-BRAF interaction. Gene expression profiles for control KRAS ^WT , KRAS ^G12V and KRAS ^G12D transfected cells were obtained after cell clone selection and RT-PCR screening. Extensive qPCR was performed to confirm microarray data.     

KIT is dispensable for physiological organ vascularisation in the embryo

Blood vessels form vast networks in all vertebrate organs to sustain tissue growth, repair and homeostatic metabolism, but they also contribute to a range of diseases with neovascularisation. It is, therefore, important to define the molecular mechanisms that underpin blood vessel growth. The receptor tyrosine kinase KIT is required for the normal expansion of hematopoietic progenitors that arise during embryogenesis from hemogenic endothelium in the yolk sac and dorsal aorta. Additionally, KIT has been reported to be expressed in endothelial cells during embryonic brain vascularisation and has been implicated in pathological angiogenesis. However, it is neither known whether KIT expression is widespread in normal organ endothelium nor whether it promotes blood vessel growth in developing organs. Here, we have used single-cell analyses to show that KIT is expressed in endothelial cell subsets of several organs, both in the adult and in the developing embryo. Knockout mouse analyses revealed that KIT is dispensable for vascularisation of growing organs in the midgestation embryo, including the lung, liver and brain. By contrast, vascular changes emerged during late-stage embryogenesis in these organs from KIT-deficient embryos, concurrent with severe erythrocyte deficiency and growth retardation. These findings suggest that KIT is not required for developmental tissue vascularisation in physiological conditions, but that KIT deficiency causes foetal anaemia at late gestation and thereby pathological vascular remodelling.