Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies worldwide. The incidence of NHL has been rising for several decades; however, in the last 20 years, it reached a plateau. NHL incidence among males is significantly higher than in females. In addition to gender itself, gravidity has a protective role against NHL occurrence. Gender also matters in terms of NHL clinical characteristics. For example, female predominance was found in three extra-nodal sites (the breast, thyroid, and the respiratory system) occasionally involved in NHL. The diagnosis of NHL during pregnancy is associated with a unique clinical behavior. It is usually diagnosed in the second or third trimester and in advanced stage. Furthermore, the histological subtype is highly aggressive, and reproductive organ involvement is common. The reduced rate of NHL among females may be explained by direct effects of estrogens on lymphoma cell proliferation or by its effect on anti-tumor immune response. Gender has an important role in responsiveness to standard B cell NHL treatment. Among older adults, women benefited more from the addition of the anti-CD20 antibody rituximab to standard chemotherapy regimens. This phenomenon can be explained by the difference in clearance rate of rituximab that was found to be significantly lower among older females than older males. In mantle cell lymphoma, women receiving lenalidomide have higher rates of response. An understanding of the mechanisms responsible for gender-associated NHL differences will ultimately improve the clinical approach, allowing for a more accurate assessment of prognosis and patient-tailored treatment.
Gaucher disease (GD) is an inherited lysosomal disorder, originating from deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Normally, GCase hydrolyzes glucocerebroside (GC) to glucose and ceramide; however, impaired activity of this enzyme leads to the accumulation of GC in macrophages, termed "Gaucher cells". GD is associated with hepatosplenomegaly, cytopenias, skeletal complications and in some forms involves the central nervous system.
Coagulation abnormalities are common among GD patients due to impaired production and chronic consumption of coagulation factors. Bleeding phenomena are variable (as are other symptoms of GD) and include mucosal and surgical hemorrhages.
Four main etiological factors account for the hemostatic defect in GD: thrombocytopenia, abnormal platelet function, reduced production of coagulation factors, and activation of fibrinolysis. Thrombocytopenia relates not only to hypersplenism and decreased megakaryopoiesis by the infiltrated bone marrow but also to immune thrombocytopenia. Autoimmunity, especially the induction of platelet antibody production, might cause persistent thrombocytopenia.
Enzyme replacement therapy reverses only part of the impaired coagulation system in Gaucher disease. Other therapeutic and supportive measures should be considered to prevent and/or treat bleeding in GD. Gaucher patients should be evaluated routinely for coagulation abnormalities especially prior to surgery and dental and obstetric procedures.
The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.
Genetic aberrations have become a dominant factor in the stratification of myeloid malignancies. Cytogenetic and a few mutation studies are the backbone of risk assessment models of myeloid malignancies which are a major consideration in clinical decisions, especially patient assignment for allogeneic stem cell transplantation. Progress in our understanding of the genetic basis of the pathogenesis of myeloid malignancies and the growing capabilities of mass sequencing may add new roles for the clinical usage of genetic data. A few recently identified mutations recognized to be associated with specific diseases or clinical scenarios may soon become part of the diagnostic criteria of such conditions. Mutational study may also advance our capabilities for a more efficient patient selection process, assigning the most effective therapy at the best timing for each patient. The clinical utility of genetic data is anticipated to advance further with the adoption of deep sequencing and next-generation sequence techniques. We herein suggest some future potential applications of sequential genetic data to identify pending deteriorations at time points which are the best for aggressive interventions such as allogeneic stem cell transplantation. Genetics is moving from being mostly a prognostic factor to become a multitasking decision support tool for hematologists. Physicians must pay attention to advances in molecular hematology as it will soon be accessible and influential for most of our patients.
Background: The positive effects of ozone therapy have been described in many gastrointestinal disorders. The mechanisms of this positive effect of ozone therapy are poorly understood. The purpose of the present study was to investigate whether the use of ozone may potentiate the gut intestinal mucosal homeostasis in a rat model.
Methods: Adult rats weighing 250–280 g were randomly assigned to one of three experimental groups of 8 rats each: 1) Control rats were given 2 ml of water by gavage and intraperitoneally (IP) for 5 days; 2) O3-PO rats were treated with 2 ml of ozone/oxygen mixture by gavage and 2 ml of water IP for 5 days; 3) O3-IP rats were treated with 2 ml of water by gavage and 2 ml of ozone/oxygen mixture IP for 5 days. Rats were sacrificed on day 6. Bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, and cell proliferation and apoptosis were evaluated following sacrifice.
Results: The group of O3-IP rats demonstrated a greater jejunal and ileal villus height and crypt depth, a greater enterocyte proliferation index in jejunum, and lower enterocyte apoptosis in ileum compared to control animals. Oral administration of the ozone/oxygen mixture resulted in a less significant effect on cell turnover.
Conclusions: Treatment with an ozone/oxygen mixture stimulates intestinal cell turnover in a rat. Intraperitoneal administration of ozone resulted in a more significant intestinal trophic effect than oral administration.
The endocannabinoid system is involved in a host of homeostatic and physiologic functions, including modulation of pain and inflammation. The specific roles of currently identified endocannabinoids that act as ligands at endogenous cannabinoid receptors within the central nervous system (primarily but not exclusively CB1 receptors) and in the periphery (primarily but not exclusively CB2 receptors) are only partially elucidated, but they do exert an influence on nociception. Exogenous plant-based cannabinoids (phytocannabinoids) and chemically related compounds, like the terpenes, commonly found in many foods, have been found to exert significant analgesic effects in various chronic pain conditions. Currently, the use of Δ9-tetrahydrocannabinol is limited by its psychoactive effects and predominant delivery route (smoking), as well as regulatory or legal constraints. However, other phytocannabinoids in combination, especially cannabidiol and β-caryophyllene, delivered by the oral route appear to be promising candidates for the treatment of chronic pain due to their high safety and low adverse effects profiles. This review will provide the reader with the foundational basic and clinical science linking the endocannabinoid system and the phytocannabinoids with their potentially therapeutic role in the management of chronic pain.
Objective: To assess the association between normal CA125 levels at diagnosis of epithelial ovarian carcinoma (EOC) with prognostic factors and with outcome.
Methods: The study group consisted of histologically confirmed EOC patients with normal pretreatment CA125 levels, and the controls consisted of EOC patients with elevated (≥35 U/mL) pretreatment CA125 levels, diagnosed and treated between 1995 and 2012. Study and control group patients fulfilled the following criteria: 1) their pretreatment CA125 levels were assessed; 2) they had full standard primary treatment, i.e. cytoreductive surgery and cisplatin-based chemotherapy; and 3) they were followed every 2–4 months during the first two years and every 4–6 months thereafter.
Results: Of 114 EOC patients who fulfilled the inclusion criteria, 22 (19.3%) had normal pretreatment CA125 levels. The control group consisted of the remaining 92 patients with ≥35 U/mL serum CA125 levels pretreatment. The proportion of patients with early-stage and low-grade disease, with optimal cytoreduction, and with platin-sensitive tumors was significantly higher in the study group than in the control group. The progression-free survival (PFS) and overall survival (OS) were significantly higher in the study group than in the control group on univariate analysis but not on multivariate analysis.
Conclusion: It seems that a normal CA125 level at diagnosis in EOC may also be of prognostic significance for the individual patient.
Otto Heinrich Warburg (1883–1970; not to be confused with the Zionist of the same name) was a member of an illustrious Jewish family, known for some five centuries. From humble beginnings, the family became prominent in the world for their contributions to all aspects of society. The son of a German mother and a Jewish (converted) father, Otto H. Warburg became a major contributor to medical science in the field of cancer research. Considered for Nobel Prize more than once, he finally received it in 1931 for his discovery of the nature and mode of action of the cellular respiratory enzyme. Warburg’s personality was controversial: he was intolerant of opposing scientific views yet tolerant toward Nazi abuses. Accused of collaboration under the Nazi regime, Otto H. Warburg was nevertheless readmitted to the global scientific community after World War II. His contribution to cancer research remains influential to this day and has been superseded by discoveries that have built upon his work.
This paper is provided for the convenience of our readers and represents a full edited transcription of the Rambam Grand Rounds Lecture by Dr. Richard Horton, Editor-in-Chief of The Lancet. The lecture was given on October 2, 2014. The Editorial Board wishes to express its gratitude to Dr. Horton for giving permission to present his Rambam Grand Rounds lecture in Rambam Maimonides Medical Journal, in both the original video format and in this printed form.
In both primary care and consultative practices, patients presenting with fibromyalgia (FM) often have other medically unexplained somatic symptoms and are ultimately diagnosed as having central sensitization (CS). Central sensitization encompasses many disorders where the central nervous system amplifies sensory input across many organ systems and results in myriad symptoms. A pragmatic approach to evaluate FM and related symptoms, including a focused review of medical records, interviewing techniques, and observations, is offered here, giving valuable tools for identifying and addressing the most relevant symptoms. At the time of the clinical evaluation, early consideration of CS may improve the efficiency of the visit, reduce excessive testing, and help in discerning between typical and atypical cases so as to avoid an inaccurate diagnosis. Discussion of pain and neurophysiology and sensitization often proves helpful.
