The Y-box binding protein YB-1 is associated with progressive disease and mediates survival and drug resistance in multiple myeloma

Current knowledge about molecular mechanisms underlying disease progression and drug resistance in multiple myeloma (MM) is still limited. Here, we analyzed the potential pathogenetic role of the Y-box binding protein YB-1 in MM. YB-1 is a member of the cold-shock domain protein superfamily and involved in various cellular functions such as proliferation. Immunohistochemical analyses revealed that neither normal bone marrow (BM) plasma cells (PCs), premalignant PCs of patients with monoclonal gammopathy of unknown significance (MGUS), nor MM cells with a mature morphology showed expression of YB-1 in situ. In contrast, YB-1 was strongly expressed in situ in normal PC precursor blasts as well as in a MM subset and in vitro in all of the evaluated MM cell lines. The YB-1-expressing MM cells were characterized by an immature morphology and a highly proliferative phenotype as defined by Ki 67 expression. We observed that siRNA-mediated knockdown of YB-1 decreased proliferation and induced apoptosis in MM cells even in the presence of BM stromal cells. Furthermore, we found that overexpression of YB-1 mediated resistance toward doxorubicin-induced apoptosis in MM cells. Thus, YB-1 contributes to disease progression, survival, and drug resistance in MM and might therefore provide an attractive therapeutic target.     

A phase III randomized,multicentre, double blind,active controlled trial to compare the efficacy and safety of two different anagrelide formulations in patients with essential thrombocythaemia – the TEAM-ET 2·0 trial

Anagrelide is an established treatment option for essential thrombocythaemia (ET). A prolonged release formulation was developed with the aim of reducing dosing frequency and improving tolerability, without diminishing efficacy. This multicentre, randomized, double blind, active-controlled, non-inferiority trial investigated the efficacy, safety and tolerability of anagrelide prolonged release (A-PR) over a reference product in high-risk ET patients, either anagrelide-naïve or -experienced. In a 6 to 12-week titration period the individual dose for the consecutive 4-week maintenance period was identified. The primary endpoint was the mean platelet count during the maintenance period (3 consecutive measurements, day 0, 14, 28). Of 112 included patients 106 were randomized. The mean screening platelet counts were 822 × 10⁹/l (95% confidence interval (CI) 707–936 × 10⁹/l) and 797 × 10⁹/l (95% CI 708–883 × 10⁹/l) for A-PR and the reference product, respectively. Both treatments effectively reduced platelet counts, to mean 281 × 10⁹/l for A-PR (95% CI 254–311) and 305 × 10⁹/l (95% CI 276–337) for the reference product (P < 0·0001, for non-inferiority). Safety and tolerability were comparable between both drugs. The novel prolonged-release formulation was equally effective and well tolerated compared to the reference product. A-PR provides a more convenient dosing schedule and will offer an alternative to licensed immediate-release anagrelide formulations.     

Severe Intraoperative Bronchospasm Treated with a Vibrating-Mesh Nebulizer

Bronchospasm and status asthmaticus are two of the most dreaded complications that a pediatric anesthesiologist may face. With the occurrence of severe bronchospasm and the inability to ventilate, children are particularly vulnerable to apnea and ensuing hypoxia because of their smaller airway size, smaller lung functional residual capacity, and higher oxygen consumption rates than adults. Nebulized medication delivery in intubated children is also more difficult because of smaller endotracheal tube internal diameters. This case demonstrates the potentially lifesaving use of a vibrating-mesh membrane nebulizer connected to the anesthesia circuit for treating bronchospasm.Key Words: Asthma, Bronchospasm, Nasal intubation, Pediatric dental anesthesia, Vibrating-mesh, nebulizerAsthma is an episodic disease characterized by hyperreactive bronchi, chronic airway inflammation, and airflow obstruction during expiration. Bronchospasm is caused by spasmodic contraction of the bronchial smooth muscle. Status asthmaticus is bronchospasm that does not respond to standard treatments, which include intravenous (IV), inhaled, and subcutaneous (SQ) interventions. It is estimated that 9.6 million children in the USA have been diagnosed with asthma. This represents approximately 13% of the total pediatric population.^1,2 The incidence of asthma is higher in urban areas, in children of low socioeconomic status, and in those with a history of atopy.^3,4 The area in which our institution is located (Bronx, New York) has the highest incidence of asthma in New York State.^3,4 The current report presents a case of bronchospasm in a 3-year-old child that was refractory to all usual treatments. A therapy not previously reported as being used in the operating room, a vibrating-mesh membrane nebulizer (Aeroneb Professional Nebulizer [APN] System, AG-AP6000-US, Aerogen Ltd, Ireland), was used to successfully relieve this episode.     

Fatal case of ectopic enterobiasis: Enterobius vermicularis in the kidneys

Enterobius vermicularis is one of the most common intestinal parasites found in humans. They commonly infest the terminal ileum and large intestine, and are usually considered an innocuous parasite that can be easily eradicated with proper treatment. However, extraintestinal migration of worms, although very rare, may lead to severe health disorders or even death. This article, reports the first fatal case of ectopic enterobiasis known to the authors, which developed in an adult patient with E. vermicularis infection, causing perforation of the large intestine and generalized bacterial peritonitis. Despite emergency laparotomy, the patient died from septic shock on the day after surgery. During pathological examination, worms were found not only in the large intestine, but also in the renal parenchyma; worm eggs were found deposited in the lungs as well.     

The temporary effect of short-term endotracheal intubation on vocal function

The objective of the study was to assess and perceive the vocal and pharyngeal symptoms and acoustic changes of voice after short-term endotracheal intubation and to evaluate the relation between these changes and the endotracheal tube parameters, number of intubation attempts, duration of anaesthesia, experience of anaesthesiologist. A total of 108 patients were evaluated preoperatively, 1–2 and 24 h after extubation. The vocal and pharyngeal symptoms, voice acoustic characteristics and maximum phonation time (MPT) were evaluated to find the relationship with endotracheal tube parameters, number of intubation attempts, duration of anaesthesia, experience of anaesthesiologist. All vocal and pharyngeal symptoms increased significantly at 24 h and remained significantly increased at 24 h after general anaesthesia. The vocal acoustic parameters changed significantly at 1–2 h: decrease of MPT and increase relative average perturbation were recorded. The day after the short-term intubation: only noise to harmony ratio and habitual pitch remains significantly changed. The most important endotracheal tube parameters that affect significantly (P value <0.05) the vocal function were the size of tube, cuff volume and number of intubation attempts. In relation to the anaesthesia, the changes of the acoustic parameters did not associate significantly with the anaesthesia-related parameters. No statistically significant relationship between experience of an anaesthesiologist and changes of the voice after anaesthesia was detected. Though being short-term, endotracheal anaesthesia is an invasive procedure, and its temporary influence on vocal function is important.     

Partial aortic occlusion and cerebral venous steal: venous effects of arterial manipulation in acute stroke

Acute ischemic stroke therapy emphasizes early arterial clot lysis or removal. Partial aortic occlusion has recently emerged as an alternative hemodynamic approach to augment cerebral perfusion in acute ischemic stroke. The exact mechanism of cerebral flow augmentation with partial aortic occlusion remains unclear and may involve more than simple diversion of arterial blood flow from the lower body to cerebral collateral circulation. The cerebral venous steal hypothesis suggests that even a small increase in tissue pressure in the ischemic area will divert blood flow to surrounding regions with lesser tissue pressures. This may cause no-reflow (absence of flow after restoration of arterial patency) in the ischemic core and "luxury perfusion" in the surrounding regions. Such maldistribution may be reversed with increased venous pressure titrated to avoid changes in intracranial pressure. We propose that partial aortic occlusion enhances perfusion in the brain by offsetting cerebral venous steal. Partial aortic occlusion redistributes blood volume into the upper part of the body, manifested by an increase in central venous pressure. Increased venous pressure recruits the collapsed vascular network and, by eliminating cerebral venous steal, corrects perifocal perfusion maldistribution analogous to positive end-expiratory pressure recruitment of collapsed airways to decrease ventilation/perfusion mismatch in the lungs.     

Focal epithelial hyperplasia: Case report

The purpose of the present article is to present a 15 year-old patient with focal epithelial hyperplasia and to review the references on the subject-related etiological, pathological, diagnostic and treatment aspects. Focal epithelial hyperplasia is a rare human papilloma virus (HPV) related to oral lesion with very low frequency within our population. Surgical treatment with a biopsy was performed, acanthosis and parakeratosis are consistent histopathological features, since the patient had no history of sexual contact and HIV infection, the virus was probably acquired from environmental sources.