Biomedicine Hub最新文献

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. This paper sets out the potential of biomarker testing, the unfolding precision and range of possible diagnosis and prediction, and the many obstacles to adoption. It offers case studies of biomarker testing in breast, ovarian, prostate, lung, thyroid and colon cancers, and derives specific lessons as to the potential and actual use of each of them. It also draws lessons about how to improve access and alignment, and to remedy the data deficiencies that impede development. And it suggests solutions to outstanding issues - notably including funding and the tangled web of obtaining reimbursement or equivalent coverage that Europe's fragmented health system implies. It urges a European evolution towards an initial minimum testing scenario, which would guarantee universal access to a suite of biomarker tests for the currently most common conditions, and, further into the future, to an optimum testing scenario in which a much wider range of biomarker tests would be introduced and become part of a more sophisticated health system articulated around personalised medicine. For exploiting genomics to the full, it argues the need for a new policy framework for Europe. Biomarker testing is not an issue that can be treated in isolation, since the purpose of testing is to improve health. Its use is therefore always closely linked to specific health challenges and needs to be viewed in the broader policy context in the EU and more widely. The paper is the result of extensive engagement with experts and decision makers to develop the framework, and consequently represents a wide consensus of views on how healthcare systems should respond from push and pull factors at local, national and cross-border and EU level. It contains strong views and clear recommendations springing from the convictions of patients, clinicians, academics, medicines authorities, HTA bodies, payers, the diagnostic, pharmaceutical and ICT industries, and national policy makers.

Some chemicals act as human carcinogens in various organ systems including the skin. Mice have been an ideal model to study a wide variety of chemical carcinogens because the pathogenesis in that species often mirrors that in humans. However, different mouse strains vary in their susceptibility to these agents. Thus, reliance on a single strain may lead to inaccurate findings. 2-Ethylhexyl acrylate (2-EHA) is an acrylate used as a co-monomer in the production of polymer resins for adhesives, latex paints, cross-linking agents, finishes for textiles and leather, and paper coatings. Monomer exposure may occur in occupational settings where it is produced or used; the only exposure that may occur to consumers or construction personnel is trace amounts in the final polymer product. There are no reports of cancer in humans caused by exposure to 2-EHA. However, 2-EHA has been reported to cause cancer in one strain of mice. This is an important issue since recommendations about its safety in humans depend, in part, on information derived from animal studies. We reviewed the literature on the preclinical effects of acrylates on skin carcinogenesis in C3H/HeJ mice, which can be criticized because of peculiarities in the immunological composition of that strain, the lack of rigorous histopathologic characterization of tumors that developed, the high doses of 2-EHA that were used for evaluation, and the lack of reproducibility in a second strain of mice. The C3H/HeJ mouse model is not ideal as it has a mutation in Toll-like receptor 4 (TLR4) that impairs its innate and adaptive immune responses. Inconsistencies in the histological evaluation of tumors induced in C3H/HeJ mice provide further evidence that the tumorigenic effect of 2-EHA was strain specific, a result of chronic inflammation during the promotion stage and/or a skewed immune response caused by the TLR4 mutation. In conclusion, 2-EHA has not convincingly been demonstrated to have skin carcinogenic activity to date. More relevant mouse models that mimic human squamous cell carcinoma, basal cell carcinoma, and melanoma with amounts that do not exceed a maximum tolerated dose are needed to assess the carcinogenic effects of 2-EHA.

Infantile hemangioma (IH) is the most common vascular tumor in infancy, and its physiopathology is not fully understood. Nevertheless, a hypoxic insult may be an essential element for the formation of an IH. Herein, we describe a case of a 25-week premature newborn who developed an IH after a post-burn scar and its evolution.

In the past decades, the key roles of most microRNA in dermatosis and skin development have been explored one after another. Among them, microRNA-31 (miR-31) has a prominent role in the regulation of keratinocytes. Numerous studies show that miR-31 can positively regulate the proliferation, differentiation and cell activity of keratinocytes via regulating the NF-κB, RAS/MAPK, Notch signaling pathways, and some cytokines. At present, the interaction between miR-31 and the NF-κB signaling pathway in keratinocytes is a hot research topic. The positive feedback loop formed by miR-31 and NF-κB signaling may bring new ideas for the prevention of psoriasis. The abnormal state of keratinocytes is usually the pathological basis of many skin and immune system diseases. Therefore, strengthening the ability to regulate keratinocytes may be a breakthrough for a variety of diseases. At the same time, miR-31's capacity to accelerate wound healing via positively regulating keratinocytes should be further investigated in the treatment of chronic ulcers and trauma.

The present case of angioleiomyoma of the nasal cavity in a 59-year-old male is unique, being the first case from North India and also because of its unique area of origin. The patient was referred to the Ear, Nose and Throat Outpatient Department with a diagnosis of an asymptomatic nasal mass. Biopsy done on the mass in another hospital reported angiofibroma. Excision was done after all relevant investigations. Histopathology revealed diagnosis of angioleiomyoma. Immunohistochemistry revealed desmin, SMA, and H-caldesmon positivity, consistent with the diagnosis of angioleiomyoma. Our case report thus highlights the im-portance of including this diagnosis in the differential diagnoses of nasal masses.

Since developments are global in the healthcare arena, more should be done to align EU and other big markets' regulatory practices for rare disease patients. Notwithstanding efforts and cooperation between the US and EU aimed to harmonize their strategic plans in the field of orphan drugs, regulatory criteria and procedures to gain the designation, terms and classifications should be still harmonised. Aligning the criteria of prevalence and support to orphan medicines in the various jurisdictions internationally, would facilitate patient recruitment eventually at global level, so as to gain the data and the biological insights required to identify biomarkers and appropriate endpoints needed for progressing clinical development. A conducive regulatory environment can further support the development of medicines to treat rare diseases. Overall there is a need for joined-up regulatory process coordination. Better integration of regulatory pathways and better integration of regulatory systems, such as scientific tools and methods to generate evidence, would be helpful. There is a need to revise and agree the current frameworks to be improved which will take into account the considerations and challenges to diagnose and treat different rare diseases and improve quality of life. Deliberative processes with multi-stakeholders' involvement for reimbursement should be considered. This paper explores the successes and limitation of both the regulation and its implementation mechanisms in the current regulatory context, and suggests some improvements that could maximise its benefits and boost rare disease research even further.

Background: Duodenal duplication cysts are rare gastrointestinal tract malformations. Most patients experience symptom onset in the first decade of life. This review aims to examine clinical presentation, management strategies and outcomes of duodenal duplication cysts in childhood.

Methods: A Pubmed/Medline (http://www.ncbi.nlm.nih.gov/pubmed/) search in October 2019 for articles published since 1999 using the keywords "duodenal duplication cyst," "child" and "newborn" was carried out. Clinical symptoms, complications, diagnostic examinations, treatment options and outcomes were analyzed and tabulated.

Results: There were 41 citations in the literature providing adequate descriptions of 45 cases of duodenal duplication cysts. The age of presentation ranged from newborn to 18 years. The median interval between initial presentation and definitive diagnosis and treatment was 17 months (range: 2 months to 12 years). Overall, 67% of cases presented with abdominal pain, and 43% were complicated with pancreatitis. Different surgical and endoscopic therapeutic strategies were reported.

Conclusions: Duodenal duplication cysts may be associated with life-threatening complications and/or recurrent symptoms, impairing quality of life. Early recognition of patients who demonstrate suggestive signs and symptoms is important to ensure success of treatment. This review may be useful to highlight the main diagnostic aspects and limit the risk of a delayed diagnosis.

Congenital laryngeal stenosis is a rare and unusual anomaly that usually presents in the first minutes after delivery as severe life-threatening respiratory distress. It may exist as an isolated entity or in association with other congenital malformations, in particular cardiac anomalies. In this paper, we present the case of an infant with prenatal suspicion of tetralogy of Fallot. Immediately after delivery, the patient required intubation, which proved difficult. He was eventually diagnosed with laryngeal stenosis requiring laryngological treatment.

Background: Gestational diabetes mellitus (GDM), a pregnancy complication, is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Vitamin D deficiency and insufficiency has recently been recognized as a contributing factor to the pathogenesis of GDM, and this link might be associated with hyperglycemia, insulin resistance, and inflammation, which are implicated in GDM.

Objectives: This study aims at investigating the relationship between vitamin D, fasting plasma glucose (FPG), insulin, zinc, ferritin, and high-sensitivity C-reactive protein (CRP) in GDM.

Method: A case-control study in which 80 women attending the antenatal clinic of University College Hospital (UCH), Ibadan, Nigeria, were recruited; the women were grouped into controls (40 nondiabetic pregnant women) and cases (40 pregnant women with GDM). Blood samples were taken at the second trimester, and metabolites were quantified by standard laboratory methods. Student's t test and Pearson correlation were used to compare variables and determine the relationship between variables, respectively.

Results: Results showed significant (p < 0.05) low levels of serum vitamin D and zinc, and significant (p < 0.05) higher levels of FPG and serum insulin, ferritin, and CRP in the GDM group compared to the control group. In the GDM group, a positive weak relationship was observed between vitamin D and zinc (r = 0.18, p < 0.05), while vitamin D was inversely correlated with FPG, serum insulin, ferritin, and CRP (r = -0.23, -0.21, -0.20, -0.46, respectively, p < 0.05).

Conclusion: This study suggests that hypovitaminosis D might be associated with glucose intolerance, insulin insensitivity, and inflammation, which are factors implicated in the development and progression of GDM.