Project description:Congenital cataract is a rare eye disease, one of the leading treatable causes of low vision in children worldwide. Hereditary cataracts can be divided in syndromic and non-syndromic cataracts. Early diagnosis in congenital cataracts is key to reach good visual function. Current surgical techniques, that combine microincision cataract extraction and primary intraocular lens (IOL) implantation, have improved childhood cataract outcome. Complications include posterior capsule opacification (PCO), aphakic or pseudophakic glaucoma, uveitis, pupil displacement and IOL decentration. A recent study using a modified Delphi approach identified areas of consensus and disagreement in the management of pediatric cataract. A consensus or near consensus was achieved for 79% of the questions, however 21% of the questions remained controversial, as for IOL implantation strategy. Congenital cataracts show a highly variable phenotype and genotype, and can be related to different mutations, genetic variance, and other risk factors. Congenital cataracts can be associated with other ocular developmental abnormalities, including microphthalmia, microcornea, or aniridia and with systemic findings. Next-generation sequencing (NGS) and forthcoming new ultra-high-throughput sequencing represent excellent tools to investigate the genetic causes of congenital cataracts. A better recognition of different clinical presentations and underlying etiologies of congenital cataracts may lead to the development of new approaches to improve visual outcome after cataract surgery and promote early detection of systemic associated syndromes.
Project description:This review focuses on recent developments in the diagnosis, treatment, management, and strategies for the prevention and control of cutaneous leishmaniasis (CL) caused by both Old and New World Leishmania species. CL is caused by the vector-borne protozoan parasite Leishmania and is transmitted via infected female sandflies. The disease is endemic in more than 98 countries and an estimated 350 million people are at risk. The overall prevalence is 12 million cases and the annual incidence is 2-2.5 million. The World Health Organization considers CL a severely neglected disease and a category 1 emerging and uncontrolled disease. The management of CL differs from region to region and is primarily based on local experience-based evidence. Most CL patients can be treated with topical treatments, but some Leishmania species can cause mucocutaneous involvement requiring a systemic therapeutic approach. Moreover, Leishmania species can vary in their sensitivity to available therapeutic options. This makes species determination critical for the choice of treatment and the clinical outcome of CL. Identification of the infecting parasite used to be laborious, but now the Leishmania species can be identified relatively easy with new DNA techniques that enable a more rational therapy choice. Current treatment guidelines for CL are based on poorly designed and reported trials. There is a lack of evidence for potentially beneficial treatments, a desperate need for large well-conducted studies, and standardization of future trials. Moreover, intensified research programs to improve vector control, diagnostics, and the therapeutic arsenal to contain further incidence and morbidity are needed.
Project description:Neuropathic pain is defined as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system".Characteristic symptoms include an increased evoked pain response to noxious (hyperalgesia) and innocuous (allodynia) stimuli, spontaneous pain, shooting electric shock like pain. Sensory deficits can also exist.Available treatments are not adequate in many patients due to many factors including the complexity of the pain state, disease progression, intolerable side effects and low analgesic efficacy.A number of peripheral, spinal and supraspinal mechanisms of hyperexcitability underlie neuropathic pain, these include changes in the activity and expression of voltage gated sodium, calcium and potassium channels, as well as TRPV1 channels and alterations in the activity of neuroimmue pathways.NeP patients often experience depression, anxiety, sleep disturbances etc. alongside their pain. These co-morbidites significantly reduce quality of life and as such are key treatment considerations..Improved understanding of NeP mechanisms is encouraging targeting of treatment to the mechanisms that produce painful symptoms as opposed to the etiology of disease.
Project description:Purpose of reviewIn the present review, we summarize the recent developments in the management of germ cell tumors (GCTs).Recent findingsTreatment-related acute and late-onset toxicity remains a key challenge in the management of GCTs. Recent data show that patients with large retroperitoneal lymph node metastases are at increased risk of venous thromboembolism and may benefit from prophylactic anticoagulation. Predictive models have been developed to identify patients with residual retroperitoneal lymph node masses who are more likely to benefit from surgical resection. However, their clinical use remains hampered by relatively low accuracy. There are currently multiple conventional-dose chemotherapy (CDCT) options for salvage therapy in patients with refractory or recurrent disease. In addition, more efficacious high-dose chemotherapy (HDCT) regimens continue to be developed. The role of salvage CDCT versus HDCT is currently being prospectively investigated.Finally, intratumoral heterogeneity is a common finding in cancer and an obvious observation in GCTs. Despite intratumoral heterogeneity, recent studies on nonseminomatous GCT have identified distinct histological subgroups and a potentially lethal clinical phenotype. Importantly, comprehensive molecular profiling so far has not elucidated the biologic basis or the clinical underpinnings of intratumoral heterogeneity in GCTs.SummaryRemaining challenges to be addressed include minimizing therapeutic toxicity and improving outcomes in patients with refractory/recurrent GCTs or malignant transformation of teratomas.
Project description:The current treatment of patients with acute myeloid leukaemia yields poor results, with expected cure rates in the order of 30-40% depending on the biological characteristics of the leukaemic clone. Therefore, new agents and schemas are intensively studied in order to improve patients' outcomes. This review summarizes some of these new paradigms, including new questions such as which anthracycline is most effective and at what dose. High doses of daunorubicin have shown better responses in young patients and are well tolerated in elderly patients. Monoclonal antibodies are promising agents in good risk patients. Drugs blocking signalling pathways could be used in combination with chemotherapy or in maintenance with promising results. Epigenetic therapies, particularly after stem cell transplantation, are also discussed. New drugs such as clofarabine and flavopiridol are reviewed and the results of their use discussed. It is clear that many new approaches are under study and hopefully will be able to improve on the outcomes of the commonly used '7+3' regimen of an anthracycline plus cytarabine with daunorubicin, which is clearly an ineffective therapy in the majority of patients.
Project description:Dry age-related macular degeneration (AMD), also called geographic atrophy, is characterized by the atrophy of outer retinal layers and retinal pigment epithelium (RPE) cells. Dry AMD accounts for 80% of all intermediate and advanced forms of the disease. Although vision loss is mainly due to the neovascular form (75%), dry AMD remains a challenge for ophthalmologists because of the lack of effective therapies. Actual management consists of lifestyle modification, vitamin supplements, and supportive measures in the advanced stages. The Age-Related Eye Disease Study demonstrated a statistically significant protective effect of dietary supplementation of antioxidants (vitamin C, vitamin E, beta-carotene, zinc, and copper) on dry AMD progression rate. It was also stated that the consumption of omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid and eicosapentaenoic acid, has protective effects. Other antioxidants, vitamins, and minerals (such as crocetin, curcumin, and vitamins B9, B12, and B6) are under evaluation, but the results are still uncertain. New strategies aim to 1) reduce or block drusen formation, 2) reduce or eliminate inflammation, 3) lower the accumulation of toxic by-products from the visual cycle, 4) reduce or eliminate retinal oxidative stress, 5) improve choroidal perfusion, 6) replace/repair or regenerate lost RPE cells and photoreceptors with stem cell therapy, and 7) develop a target gene therapy.
Project description:Tuberculosis infection (TBI) is defined as a state of infection in which individuals host live Mycobacterium tuberculosis with or without clinical signs of active TB. It is now understood as a dynamic process covering a spectrum of responses to infection resulting from the interaction between the TB bacilli and the host immune system. The global burden of TBI is about one-quarter of the world's population, representing a reservoir of approximately 2 billion people. On average, 5-10% of people who are infected will develop TB disease over the course of their lives, but this risk is enhanced in a series of conditions, such as co-infection with HIV. The End-TB strategy promotes the programmatic management of TBI as a crucial endeavor to achieving global targets to end the TB epidemic. The current development of new diagnostic tests capable of discriminating between simple TBI and active TB, combined with novel short-course preventive treatments, will help achieve this goal. In this paper, we present the current situation and recent developments of management of TBI and the operational challenges.
Project description:Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease (AID) affecting mainly the ethnic groups originating from Mediterranean basin. The disease is characterized by self-limited inflammatory attacks of fever and polyserositis along with elevated acute phase reactants. FMF is inherited autosomal recessively; however, a significant proportion of heterozygotes also express the phenotype. FMF is caused by mutations in the MEFV gene coding for pyrin, which is a component of inflammasome functioning in inflammatory response and production of interleukin-1β (IL-1β). Recent studies have shown that pyrin recognizes bacterial modifications in Rho GTPases, which results in inflammasome activation and increase in IL-1β. Pyrin does not directly recognize Rho modification but probably affected by Rho effector kinase, which is a downstream event in the actin cytoskeleton pathway. Recently, an international group of experts has published the recommendations for the management of FMF. Colchicine is the mainstay of FMF treatment, and its regular use prevents attacks and controls subclinical inflammation in the majority of patients. Furthermore, it decreases the long-term risk of amyloidosis. However, a minority of FMF patients fail to response or tolerate colchicine treatment. Anti-interleukin-1 drugs could be considered in these patients. One should keep in mind the possibility of non-compliance in colchicine-non-responders. Although FMF is a relatively well-described AID and almost 20 years has passed since the discovery of the MEFV gene, there are still a number of unsolved problems about it such as the exact mechanism of the disease, symptomatic heterozygotes and their treatment, and the optimal management of colchicine resistance.
Project description:After reviewing how psychological treatment for chronic pain comes to have its current form, and summarizing treatment effectiveness, we explore several areas of development. We describe third wave therapies, such as mindfulness; we discuss what the research literature aggregated can tell us about what trials are more useful to conduct; and we outline some areas of promise and some failures to deliver on promise. The article is drawn together using the framework of the normal psychology of pain, identifying some of its most important implications for improving life for people with chronic pain.