Juvenile Adamantiades-Behçet disease

Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review

Encephalopathy in an adult with cat-scratch disease.

We report the case of a 53-year-old healthy man, presenting with confusion. The patient had been clinically diagnosed with cat-scratch disease (CSD) and prescribed a 10-day course of doxycycline orally. Approximately a week after he had completed the treatment, he was admitted to our department with confusion. Neurological examination revealed expressive dysphasia with no motor or sensory deficits. Cerebrospinal fluid (CSF) examination showed only increased content. Imaging with CT and MRI of the brain did not reveal any abnormalities, and funduscopy was normal. Serology confirmed Bartonella henselae infection. CSD-associated encephalopathy was confirmed based on the clinical manifestations, CSF findings and positive serology. The patient was treated with a combination of doxycycline and rifampin and he rapidly improved with complete neurological recovery within 7 days. Encephalopathy is an unusual manifestation of CSD in adults with excellent prognosis

NF-kappa B in colorectal cancer

Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide, responsible for more than half a million deaths annually. CRC is a multistep process that entails the accumulation of genetic/epigenetic aberrations, which lead to the simultaneous failure of protective mechanisms and the activation of tumorigenic pathways. In most cases of CRC a deregulation of the Wnt-signaling pathway is required. The transcription factor nuclear factor kappa B (NF-kappa B) has been recognized as a key player in the initiation and propagation of CRC. Under physiological conditions, NF-kappa B orchestrates the inflammatory process and participates in the modulation of various steps of cell cycle and survival. It is normally kept in an inactive state in the cytoplasm by binding to a group of inhibitory proteins. Upon receipt of a signal, its inhibitor is phosphorylated and proteolytically degraded and NF-kappa B is actively translocated to the nucleus, where it facilitates target-gene transcription. Recent experimental data reveal the important role of NF-kappa B in tumor cells as well as in the surrounding “cancerous” and reactive microenvironment. Various tumor cell-derived and contextual cues feed constantly this vicious circuitry sustaining inflammation and promoting proliferation, angiogenesis, invasion and eventually metastasis. Therefore NF-kappa B along with its upstream and downstream network presents a rational target for therapeutic interventions. Numerous small molecules, inhibitory peptides, antisense RNAs, natural compounds, as well as gene therapy strategies interfere with multiple steps of the NF-kappa I’ signaling cascade. The design of NF-kappa I’-targeted treatment may aid the efforts towards the pursuit of more efficient therapeutic measures devoid of severe systemic side-effects

Epigenetic modifications in colorectal cancer: Molecular insights and therapeutic challenges

Colorectal cancer, a leading cause of mortality worldwide, is a multistep disorder that results from the alteration of genetic and epigenetic mechanisms under contextual influence. Epigenetic aberrations, including DNA methylation, histone modifications, chromatin remodeling and non-coding RNAs, affect every aspect of tumor development from initiation to metastasis. Cancer stem cell promotion is also included in the wide spectrum of epigenetic dysregulations. Elucidation of this complex crosstalk network may offer new insights in the molecular interactions involved in the pathogenesis of colorectal carcinogenesis. In the era of translational medicine new horizons are opened for the pursuit of personalized therapeutic approaches and the development of novel and accurate diagnostic, prognostic and therapy-assessment markers. This review discusses the implications of epigenetic mechanisms in tumor biology and their applications “from bench to bedside”. (C) 2014 Elsevier B.V. All rights reserved

Targeting transcription factor corepressors in tumor cells

By being the “integration” center of transcriptional control as they move and target transcription factors, corepressors fine-tune the epigenetic status of the nucleus. Many of them utilize enzymatic activities to modulate chromatin through histone modification or chromatin remodeling. The clinical and etiological relevance of the corepressors to neoplastic growth is increasingly being recognized. Aberrant expression or function (both loss and gain of) of corepressors has been associated with malignancy and contribute to the generation of transcriptional “inflexibility” manifested as distorted signaling along certain axes. Understanding and predicting the consequences of corepressor alterations in tumor cells has diagnostic and prognostic value, and also have the capacity to be targeted through selective epigenetic regimens. Here, we evaluate corepressors with the most promising therapeutic potential based on their physiological roles and involvement in malignant development, and also highlight areas that can be exploited for molecular targeting of a large proportion of clinical cancers and their complications

Preoperative serum lactate dehydrogenase levels in colorectal and gastric cancer: a hospital-based case-control study

Aim: To reveal correlations between serum lactate dehydrogenase (LDH) levels and various clinicopathological parameters in colorectal and gastric cancer. Materials & methods: A hospital-based case control study was conducted by measuring serum LDH levels in 140 patients with colorectal cancer, 40 patients with gastric cancer and 20 hospital controls. Results: LDH levels did not differ between patients with colorectal or gastric cancer and hospital controls. In colorectal cancer, LDH values were significantly higher in T4, N2 and/or M1 cases, with high specificities and negative predictive values, but low sensitivities and positive predictive values. On the other hand, there were no significant associations in gastric cancer. Conclusion: Serum LDH levels are increased in T4, N2 and/or M1 colorectal cancer. Most patients with early-stage cancer have normal LDH values, whereas in advanced stages, some patients have increased LDH values and others have normal values

Risk Factors, Diagnosis, and Treatment of Neonatal Fungal Liver Abscess: A Systematic Review of the Literature

(1) Background: Although invasive fungal infections are a major cause of neonatal morbidity and mortality, data on the incidence and outcomes of localized abscesses in solid organs due to fungal infections are scarce. The aim of this study was to consolidate evidence and enhance our understanding on neonatal liver abscesses due to invasive fungal infections. (2) Methods: An electronic search of the PubMed and Scopus databases was conducted, considering studies that evaluated fungal liver abscesses in the neonatal population. Data on the epidemiology, clinical course, treatment, and outcome of these infections were integrated in our study. (3) Results: Overall, 10 studies were included presenting data on 19 cases of neonatal fungal liver abscesses. Candida spp. were the most common causative pathogens (94.7%). Premature neonates constituted the majority of cases (93%), while umbilical venous catheter placement, broad spectrum antibiotics, and prolonged parenteral nutrition administration were identified as other common predisposing factors. Diagnosis was established primarily by abdominal ultrasonography. Medical therapy with antifungal agents was the mainstay of treatment, with Amphotericin B being the most common agent (47%). Abscess drainage was required in four cases (21%). Eradication of the infection was achieved in the majority of cases (80%). (4) Conclusions: Even though fungal liver abscess is a rare entity in the neonatal population, clinicians should keep it in mind in small, premature infants who fail to respond to conventional treatment for sepsis, particularly if an indwelling catheter is in situ. A high index of suspicion is necessary in order to achieve a timely diagnosis and the initiation of the appropriate treatment

Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC