Articles

This study describes chemotherapy exposure, healthcare utilization, overall survival (OS) and progression-free survival (PFS) among patients diagnosed with chronic lymphoid leukemia (CLL). Newly diagnosed CLL patients who received chemotherapy were selected from the Eindhoven Cancer Registry between 1998-2011, linked on a patient-level to the PHARMO Database Network including data on in- and out-patient drug dispensings, hospitalizations and clinical laboratory measurements. Chemotherapy was classified in regimens of use based on chemotherapy combinations. OS and PFS were determined after diagnosis and after chemotherapy. Healthcare utilization was assessed in the year before diagnosis and in the year after chemotherapy. In total, 125 CLL patients received chemotherapy: 52 patients (42%) started chemotherapy within 6 months and 73 patients (58%) started chemotherapy ≥6 months after diagnosis. Mean (±SD) age was 67(±10) years and 68% was male. About 50% had one treatment line and about 25% two lines of treatment. Chlorambucil was the most common type of first line chemotherapy. Prior diagnosis, 44% were hospitalized for any cause and 94% had at least one drug dispensing. After chemotherapy, this was 43% and 98%, respectively. One-year survival rate after diagnosis was 94%. Median PFS after first treatment line was 17 months for patients starting within 6 months and 27 months for patients starting ≥6 months after diagnosis. In conclusion, most CLL patients receiving chemotherapy were treated with chlorambucil. One-year after initial diagnosis, 94% were still alive. Median PFS after first line chemotherapy ranged from 17 to 27 months, depending on the timing of chemotherapy.

Background: Multiple sclerosis (MS) is an autoimmune disorder of the central nerve system (CNS), which affects the brain and spinal cord. Experimental autoimmune encephalomyelitis (EAE) is the most commonly applied experimental model for studying the MS. The aim of this study was to determine the effects of Sesamum indicum seeds oil on Experimental Autoimmune Encephalomyelitis (EAE) in mice. Methods: Sesame oil was administrated intraperitoneally three days before immunization. IFN-γ, IL-10, IL-17 and TGF-β levels and mRNA expression in supernatant of and within cultured mononuclear cells were assessed. Results: According to our results, sesame oil treated mice demonstrated significant disease severity reduction (P=0.01 and 0.001, respectively). Treated EAE mice also represented statistically significant delay in the onset of symptoms in comparison with control group. The average IFN-γ levels and mRNA of sesame oil treated EAE mice were less than untreated EAE group. IL-10 and TGF-β levels and mRNA did not differ significantly in sesame oil treated EAE mice in comparison to untreated EAE group. IL-17 levels and mRNA were also found to be decreased significantly in treated mice in comparison to untreated mice. Conclusions: Even thoughTH1 and TH17 cells through secretion of IFN-γ and IL-17, respectively, are involved in the pathogenesis of multiple sclerosis and EAE, but IL-10 has been shown to exhibit suppressive effects on these disorders. It can be concluded that sesame oil is able to induce TH2 and TH17-related immune responses and suppress TH1 type in EAE

Drug-induced Hepatotoxicity and biologic drugs have historically been challenging in IBD. We aim to study the prevalence of hepatotoxicity in adult patients using biologic medications.

Background: The use of brain magnetic resonance imaging (MRI) for evaluation of neurological disorders has increased in the past two decades. This has led to an increased detection of incidental findings on brain MRI. The most common of these asymptomatic abnormalities are white matter lesions that are interpreted as demyelinating based on radiological criteria. However, in the absence of associated clinical symptoms suggestive of multiple sclerosis (MS), a definite diagnosis of MS can’t be made in patients with these incidental white matter lesions. These patients are diagnosed as CIS (clinically isolated syndrome) and RIS (radiologically isolated syndrome).Using the revised McDonald criteria now allows some patients who would have been diagnosed with CIS to be diagnosed as having MS before a second episode. Method: Sixty one patients, 40 females and 21 males, age ranged between 15 years and 58 years, were included in our study. In addition to a detailed medical and neurological history and examination, CSF and blood analysis for oligoclonal bands and IgG index were performed for all patients. Result: 41 patients had positive oligoclonal bands and IgG index. After clinical, MRI results and laboratory results 44 (72.1%) were diagnosed CIS and 17 (27.9%) were RIS. Conclusion: Diagnosis of MS not depend only on MRI finding but need clinical and laboratory work up including CSF and blood analysis for oligoclonal bands and IgG index to confirm diagnosis.

This review examines of the concept of a defective chloride channel in epithelial cells being a major cause of cystic fibrotic pathophysiology. The central concept of the defective chloride ion channel paradigm is that faulty CFTR protein or failed delivery of CFTR protein to the mucosal membrane of epithelial cells is the basis of cystic fibrosis. Defective placement or function of CFTR prevents hydration of bronchial mucus that is normally caused by epithelial cells; these are capable through chloride ion secretion of transporting fluid to the mucosal surface. This concept relies heavily on a paradigm taken from intestinal physiology-namely that the intestinal epithelial cell secretes chloride ion and fluid and that this has conferred heterozygote selective advantage in carriers of the cystic fibrosis gene. This present review examines the evidence for that hypothesis and assembles evidence from past studies that it is the smooth muscle cell that is of greater relevance. This review does not aim to provide an overview of current research into cystic fibrosis. The intention is to provide an overview of past research that led to the concept of a failure of epithelial cells to hydrate bronchial mucus because of compromised CFTR function. It is important to present all past evidence for aspects of the chloride secretion hypothesis and its associated heterozygote advantage concept so that the important evidential milestones can be re-assessed.

Allergen immunotherapy (AIT) is the unique curative treatment to help allergic patients to get over their allergies. With a personalized approach, AIT is the best example of precision medicine. After a century of intensive studies and innovative discoveries, allergists have in their hands many tools to orchestrate the best strategy to re-educate the hypersensitive immune systems that decrease the quality of life of their patients. This review describes both the historical and the promising acquisitions in this field, focusing the biochemical and Bioengineering tools that render an allergen more suitable for a secure, convenient and effective immunotherapy.

Chest compression is the fundamental technique in cardiopulmonary resuscitation (CPR) in patients with cardiac arrest [1]. The quality and the early implementation of CPR are essential to improve the prognosis and the chances of restoring spontaneous circulation. In the literature, there are some articles about the poor quality of chest compression [2-4]. Therefore chest compression is as crucial as alerting the emergency services or early defibrillation in the survival chain. In accordance with the guidelines, chest compressions have to be performed continuously to improve the outcome [5]. However, the efficacy of manual chest compression diminishes over time with the fatigue of the provider (which appears within minutes of starting the procedure), and is impaired during transportation manoeuvres, which expose patients to unforeseen interruptions and a deterioration in the quality du massage in terms of power and rhythm. The efficacy of manual chest compression has been reported to fall by 20% per minute [6,7]. Mechanical chest compression overcome this problem of operator fatigue by ensuring constant efficacy in terms of both quality and quantity. Even though current data show no difference between manual chest compression and automated systems in terms of survival, haemodynamic studies in animal models have shown that mechanical techniques are more effective [8].

Seizure is clinical manifestation of sudden disruption of the normal electrical activity of cortical neurons. The brain electrical activity is periodically disturbed, alteration in neural cell integrity, increase in firing impulses and spread to adjacent normal neurons result in temporary brain dysfunction with alterations in consciousness, behavior or motor function. It may be triggered by illness, infection, stress, stroke, brain tumor, or the underlying cause may not completely understand. Status epilepticus (SE) is a medical emergency and requires prompt diagnosis and treatment. Treatment includes general support measures, drugs to suppress epileptic activity and relieving the underlying condition. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. For SE treatment, benzodiazepines are the first line antiepileptic agents, and if benzodiazepines fail to control seizures, Phenytoin is usually indicated; Phenobarbital or Valproate may also be considered. For refractory SE, Propofol and Thiopental represent first line agents after careful assessment of potential risks. In refractory SE, general anesthesia may be required. There is currently no unique consensus for definite treatment option of RSE. In this review, the management protocol of seizure, assessment, monitoring, and different alternative therapy would be discussed.

Chronic asthma accounts for a significant amount of unscheduled office and emergency department (ED) visits. According to the latest World Health Organization statistics, asthma worldwide affects 300 million individuals and creates a substantial health burden by restricting the patient’s lifetime activities. Data estimate that asthma causes a loss of disability-adjusted life years over 150,000/year [1]. While most individuals with asthma can be controlled with current therapies, 5-10% of patients have difficult-to-control/refractory asthma. Severe or refractory asthma places a significant burden on the patient and often requires treatment with systemic glucocorticoids, which have significant side effects. The American Thoracic Society and the European Respiratory Society define refractory asthma as asthma that requires treatment with high-dose inhaled corticosteroids (ICS) plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or asthma that remains ‘‘uncontrolled’’ despite this aggressive therapy. To fully meet this definition the diagnosis of asthma needs to be confirmed and comorbidities addressed as well. The above are considered major criteria for severe asthma and only one needs to be present for considering the diagnosis of refractory asthma [2]. For these reasons, clinicians must learn to identify and formulate additional diagnoses of “asthma imitators” [3]. One of the more common disorders associated with difficult-to-control asthma is vocal cord dysfunction (VCD) [4]. This disorder is known by many names, but current nomenclature endorsed by European and American societies correctly refers it as “Inducible Laryngeal Obstruction” (ILO) [5]. The following case demonstrates the importance of recognizing the clinical and spirometric features of ILO when asthma remains “refractory” to multiple therapies.

Acute liver failure (ALF) in children is a severe disease with a high mortality rate. The current treatment strategies are still defective, with many cases die when liver transplantation is unavailable. The current protocol of steroids therapy improved the survival rate of hepatitis A virus (HAV)-related ALF. However, there is still a high mortality for non-HAV cases. Stem cell therapy (SCT) has been tried in experimental animals with ALF and in few adult studies with acute-on-chronic liver failure. No previous trials of SCT have been tested in children with ALF. The absence of SCT application in ALF in children could be due to some issues. These could be related to safety, sources, administration route, optimum dosage, efficacy, and survival. It is proposed that could be the future therapy if these obstacles have been well studied and solved.