Inhibition of p38 MAP kinase pathway induces apoptosis and prevents Epstein Barr virus reactivation in Raji cells exposed to lytic cycle inducing compounds

Background  

EBV lytic cycle activators, such as phorbol esters, anti-immunoglobulin, transforming growth factor β (TGFβ), sodium butyrate, induce apoptosis in EBV-negative but not in EBV-positive Burkitt's lymphoma (BL) cells. To investigate the molecular mechanisms allowing EBV-infected cells to be protected, we examined the expression of viral and cellular antiapoptotic proteins as well as the activation of signal transduction pathways in BL-derived Raji cells exposed to lytic cycle inducing agents.     

Melphalan,Prednisone, and Lenalidomide for Newly Diagnosed Myeloma: Kinetics of Neutropenia and Thrombocytopenia and Time-to-Event Results

BackgroundInitial analysis of the combination melphalan, prednisone, plus lenalidomide (MPR) showed significant antimyeloma activity in patients with untreated multiple myeloma, with neutropenia and thrombocytopenia as the most frequent side effects. This updated analysis reassessed the kinetics of neutropenia and thrombocytopenia as well as the safety and efficacy of MPR.Patients and MethodsA total of 21 patients with newly diagnosed myeloma received melphalan 0.18 mg/kg on days 1-4, prednisone 2 mg/kg on days 1-4, and lenalidomide 10 mg daily on days 1-21 for nine 28-day cycles, followed by maintenance therapy with lenalidomide 10 mg daily on days 1-21.ResultsGrade 3/4 neutropenia occurred in 52% of the patients, and granulocyte colonystimulating factor was administered in 43%. The mean neutrophil counts at the start of each MPR cycle, during nadir, and after 6 months of maintenance were 2.69 × 10⁹/L, 1.43 × 10⁹/L, and 2.11 × 10⁹/L, respectively. Grade 3/4 thrombocytopenia occurred in 24% of the patients. Platelet transfusions were required by 1 patient (5%) with a platelet count of 16 × 10⁹/L; however, no thrombocytopenia-associated bleeding was reported. The mean platelet counts at the start of each cycle, during nadir, and after 6 months of maintenance were 174 × 10⁹/L, 121 × 10⁹/L, and 158 × 10⁹/L, respectively. Median follow-up was 29.6 months, median progression-free survival was 28.5 months, and 2-year overall survival was 91%.ConclusionMPR is a promising regimen with manageable hematologic toxicity.     

Characterizing multisegment foot kinematics during gait in diabetic foot patients

Background  

The prevalence of diabetes mellitus has reached epidemic proportions, this condition may result in multiple and chronic invalidating long term complications. Among these, the diabetic foot, is determined by the simultaneous presence of both peripheral neuropathy and vasculopathy that alter the biomechanics of the foot with the formation of callosity and ulcerations. To diagnose and treat the diabetic foot is crucial to understand the foot complex kinematics. Most of gait analysis protocols represent the entire foot as a rigid body connected to the shank. Nevertheless the existing multisegment models cannot completely decipher the impairments associated with the diabetic foot.     

Nutripedia: The Fight against the Fake News in Nutrition during Pregnancy and Early Life

(1) Background. Early nutrition and lifestyle before and during pregnancy, breastfeeding, infancy, and early childhood can affect the risk of developing common non-communicable diseases during adulthood such as obesity and metabolic syndrome. To support positive long-term outcomes, it is essential to debunk fake news and provide evidence-based nutritional recommendations. “Nutripedia-Informati per Crescere” is a new tool delivering information and education on appropriate nutrition of mothers and babies during pregnancy and the first years of life. (2) Methods. Nutripedia provides the readers with evidence-based scientific contents in an easy-to-access fashion through a website, a social media page and a personalized advice app called “Nutripedia Chatbot”. (3) Results. Forty articles were published on Nutripedia website with more than 220,000 total views. Social channel activation via bloggers reached over 9 million parents. 14,698 users downloaded Nutripedia chatbot, through which a total of 1930 questions were directed to experts while over 24,000 responses were provided by the app. (4) Conclusions. The use of different communication tools delivering evidence-based nutritional information such as Nutripedia is increasing and could offer supportive strategies to provide scientific information to large audiences and contribute fighting fake news. Future research could investigate the effectiveness of this important health campaign.     

HOX D13 expression across 79 tumor tissue types

HOX genes control normal development, primary cellular processes and are characterized by a unique genomic network organization. Locus D HOX genes play an important role in limb generation and mesenchymal condensation. Dysregulated HOXD13 expression has been detected in breast cancer, melanoma, cervical cancer and astrocytomas. We have investigated the epidemiology of HOXD13 expression in human tissues and its potential deregulation in the carcinogenesis of specific tumors. HOXD13 homeoprotein expression has been detected using microarray technology comprising more than 4,000 normal and neoplastic tissue samples including 79 different tumor categories. Validation of HOXD13 expression has been performed, at mRNA level, for selected tumor types. Significant differences are detectable between specific normal tissues and corresponding tumor types with the majority of cancers showing an increase in HOXD13 expression (16.1% normal vs. 57.7% cancers). In contrast, pancreas and stomach tumor subtypes display the opposite trend. Interestingly, detection of the HOXD13 homeoprotein in pancreas‐tissue microarrays shows that its negative expression has a significant and adverse effect on the prognosis of patients with pancreatic cancer independent of the T or N stage at the time of diagnosis. Our study provides, for the first time, an overview of a HOX protein expression in a large series of normal and neoplastic tissue types, identifies pancreatic cancer as one of the most affected by the HOXD13 hoemoprotein and underlines the way homeoproteins can be associated to human cancerogenesis. © 2009 UICC     

Burkitt lymphoma versus diffuse large B‐cell lymphoma: a practical approach

Burkitt Lymphoma (BL) is listed in the World Health Organization (WHO) classification of lymphoid tumours as an “aggressive B‐cell non‐Hodgkin's lymphoma”, characterized by a high degree of proliferation of the malignant cells and deregulation of the c‐MYC gene. The main diagnostic challenge in BL is to distinguish it from diffuse large B‐cell lymphoma (DLBCL). While in children BL and DLBCL types probably do not differ clinically, and the differential diagnosis between BL and DLBCL may theoretically appear clear‐cut, in adults daily practice shows the existence of cases that have morphological features, immunophenotypic and cytogenetics intermediate between DLBCL and BL, and cannot be classified with certainty in these categories. Distinguishing between BL and DLBCL is critical, as the two diseases require different management. This review summarizes the current practical approach, including the use of a large panel of antibodies, and cytogenetic and molecular diagnostic techniques, to distinguish between BL, DLBCL and the provisional category of “B‐cell lymphoma, unclassificable, with features intermediate between diffuse large B‐cell lymphoma and Burkitt lymphoma”, now listed in the updated WHO classification. Copyright © 2009 John Wiley & Sons, Ltd.     

Reconstruction of the hypopharynx after free jejunum flap failure: is a second free jejunum transfer feasible?

Reconstruction after circumferential pharyngolaryngectomy is a challenging problem. Reconstruction methods should ensure an appropriate mucosa lining of the digestive tract, preferably already tubulized, and peristalsis. Despite the high reported success rates, the jejunum flap is still occasionally lost due to thrombosis of the pedicle and/or fistula formation. Five cases of circumferential pharyngolaryngectomy in which failure of the jejunum loop was managed with a second free or pedicle flap are presented. A second free jejunum was reliable in selected patients, depending on time of detection of flap necrosis, on bacterial control of the wound and on the vascular or general conditions. For this reason, careful monitoring of the flap and clinical signs of necrosis in the first 5 post-operative days is crucial to prevent the formation of fistulas and infection and to increase the possibility of using this kind of salvage surgery. Pedicle flaps should be used only in the event of severe complications because of their high risk of post-operative salivary fistulas.     

Positron Emission Tomography (PET) radiotracers in oncology – utility of 18F-Fluoro-deoxy-glucose (FDG)-PET in the management of patients with non-small-cell lung cancer (NSCLC)

PET (Positron Emission Tomography) is a nuclear medicine imaging method, frequently used in oncology during the last years. It is a non-invasive technique that provides quantitative in vivo assessment of physiological and biological phenomena. PET has found its application in common practice for the management of various cancers.Lung cancer is the most common cause of death for cancer in western countries.This review focuses on radiotracers used for PET scan with particular attention to Non Small Cell Lung Cancer diagnosis, staging, response to treatment and follow-up     

Lipedematous alopecia of the scalp

Lipedematous scalp is a rare disorder, mainly described in adult African-American females. We report 2 adult caucasian males with lipedematous scalp associated with androgenetic alopecia. Patients were studied by dermoscopy and histopathology; they were treated with finasteride 1 mg. In our patients, lipedematous scalp affected the occipital and the vertex areas and pathologically exhibited mild edema and thickening of the adipose subcutaneous layer. At videodermoscopy, lipedematous scalp areas showed linear areas of teleangiectasia within the scalp creases, possibly caused by compression of the superficial blood capillaries by the increased volume of the subcutaneous fat layer within the thickened scalp. Finasteride at a dose of 1 mg per day for 1 year induced mild improvement of androgenetic alopecia in one patient and stabilization of the disease in the other. The lipedematous scalps remain unchanged. Lipedematous scalp is apparently a rare disease even though the condition is probably underdiagnosed. As a matter of fact, we diagnosed lipedematous scalp in our patients during a clinical examination for androgenetic alopecia, which was the patients' complaint. The association of lipedematous scalp and androgenetic alopecia in our two patients appears to be coincidental.     

Sharing features of uncommon respiratory syncytial virus complications in infants

We describe 4 nonconsecutive cases of infants admitted to Catholic University pediatric intensive care unit (PICU) because of complicated respiratory syncytial virus (RSV) infection during winter RSV outbreaks from the year 2000 to the year 2003. A hyponatremic epileptic status (as in the first case) has been reported by several authors as a rare RSV complication, potentially leading to death. The second infant developed a serious pulmonary edema after a subglottic obstruction (croup) associated with RSV infection. The remaining 2 infants developed a pneumothorax and subcutaneous emphysema while breathing spontaneously during an RSV bronchiolitis. In all infants, a full recovery and PICU discharge was achieved despite the need for mechanical ventilation in cases 1 and 2. Increased intrapleural negative pressure or its combination with hypoxia/hypercapnia has been suggested as the common factor possibly joining these different clinical pictures.