“Targeting” renal cell carcinoma patients with “targeted” agents: Are we there yet?

The rapid approval of several novel agents, targeting the vascular endothelial growth factor or mammalian target of rapamycin pathways (sunitinib, pazopanib, sorafenib, axitinib, bevacizumab, everolimus, temsirolimus) has given to metastatic renal cell carcinoma (mRCC) patients and their treating physicians many new and effective therapeutic options. The treatment paradigm for these patients is rapidly evolving, with future studies needed to define the optimal sequencing of these new agents. Despite progresses, no validated biomarkers able to predict clinical outcome or useful to guide patient selection for treatment are currently available. Recent studies have suggested that some biomarkers, including cytokines, circulating proangiogenic factors, markers of hypoxia or targets of signaling pathways are potentially promising prognostic or predictive factors in mRCC. We present an overview of the most recent developments in identifying biomarkers for targeted therapies in advanced RCC.     

甲氨蝶呤是否能有效安全地维持全秃患者的头发再生? 一个经过严格评价议题

Alopecia areata (AA) is a common disorder causing hair loss, which can range from patches, to complete hair loss on the scalp (alopecia totalis), or involving all hair‐bearing sites (alopecia universalis). It can cause anxiety, depression and low self‐esteem. Treatment can be difficult – there are several options but they don't always work and can have unwanted side effects. Hair can in fact regrow without any treatment. The aim of this study was to assess the current evidence regarding use of a drug called methotrexate for getting hair to regrow, and then remain, in people with alopecia. The authors looked at 13 studies comprising 226 patients with alopecia varying from 30% hair loss to alopecia universalis at the start. Methotrexate was usually given with drugs called systemic corticosteroids to start hair regrowth rather than regrowth maintenance. Regrowth, defined as anything from 50% to complete regrowth, was reported in 20‐90% of patients. Relapse (meaning hair re‐grew but then fell out again) occurred in 20‐80%, with variable regrowth on retreatment. Unwanted side effects ranged from 7‐60%. The authors found insufficient evidence to conclude whether methotrexate is useful for maintaining regrowth in extensive alopecia areata. They found some evidence to suggest that hair regrowth may be started by methotrexate when used in combination with systemic corticosteroids, but it was difficult to say which of the treatments this was due to, or if the hair was going to regrow anyway. Further trials are needed.     

性事·运动·健康——话题四则

话题之一:与性"锻炼"者的对话 我在门诊接待了一对60岁开外的老年夫妻,男性老人神采奕奕,女性老人红润扑面,二老非常健谈.     

Reconstructive surgery in Peyronie’s disease: What’s new?

Surgical treatment of Peyronie’s disease (PD) is still a challenge and a gold standard approach does not exist; however the main goal is to straight penile shaft, and to restore penetrative and coital capacity. The less invasive approach aims to correct curvature without intervening directly on the fibrous plaque while the more complex “corporoplasty” applies specific geometric criteria and uses different autologous and heterologous grafts. Each approach has its pros and cons and decision-making should be tailored to the individual patient’s expectations. Other surgical options include different use of patches to cover the tunica albuginea defect, with the choice depending on the surgeon’s personal experience. Despite the wide range of autologous (buccal mucosa, vein, dermis, etc.) and heterologous grafts (bovine pericardium, swine intestinal submucosa, porcine dermis, etc.) none currently represents the real “gold standard” because the data are extremely variable and frequently not representative. Several factors seem to favor buccal mucosa grafts over inert biocompatible materials: as vital tissue, buccal mucosa tends to heal rapidly, immediately integrating with the surrounding albuginea tissue. This translates into a more rapid resumption of spontaneous erections (after 3/4 d) and sexual activity and into a reduced risk of curvature relapse and erectile dysfunction after surgery. Another advantage of the buccal mucosa graft is its low cost. In conclusion, despite the recent development of some exciting new surgical techniques we are still unable to deliver a definitive take-home message about reconstructive surgery in PD because the majority of the studies reported insufficient data. However, since it is clear that major outcomes, besides the cosmetic result, are the patient’s and partner’s satisfaction and the economic impact of each technique, we recommend they be included among the outcome assessment parameters in further studies     

Is there a ‘gut–brain–skin axis’?

Please cite this paper as: Is there a ‘gut–brain–skin axis’? Experimental Dermatology 2010; 19: 401–405. Abstract: Emerging evidence arising from interdisciplinary research supports the occurrence of communication axes between organs, such as the brain–gut or brain–skin axis. The latter is employed in response to stress challenge, along which neurogenic skin inflammation and hair growth inhibition is mediated. We now show that ingestion of a Lactobacillus strain in mice dampens stress‐induced neurogenic skin inflammation and the hair growth inhibition. In conclusion, we are introducing a hypothesis, encouraged by our pilot observations and resting upon published prior evidence from the literature, which amalgamates previously proposed partial concepts into a new, unifying model, i.e. the gut–brain–skin axis. This concept suggests that modulation of the microbiome by deployment of probiotics can not only greatly reduce stress‐induced neurogenic skin inflammation but even affect a very complex cutaneous phenomenon of (mini‐) organ transformation, i.e. hair follicle cycling. These observations raise the intriguing prospect that feeding of just the right kind of bacteria can exert profound beneficial effects on skin homoeostasis, skin inflammation, hair growth and peripheral tissue responses to perceived stress.     

Probióticos y prebióticos: ¿beneficio real en dermatología?

Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host beyond their nutritional contribution. In addition to their effects on gut homeostasis, probiotics may also regulate systemic immune and inflammatory responses. Therefore, modulating the gut microbiota by orally administered probiotics could exert positive effects on the skin. The cutaneous disease in which these effects have been most widely studied is atopic dermatitis, and greater benefits have been obtained in the prevention than in the treatment of this entity.Prebiotics, in contrast, are non-digestible food ingredients that beneficially affect the host by selectively stimulating bacterial growth and/or activity. This concept was originally developed to selectively modify the gut microflora, but in principle could be applied to modulate the composition of any microbial community, including the skin microflora.A prominent example is the skin of acne patients, in which prebiotic administration could be effective in reducing the amount of Propionibacterium acnes, and at the same time in preserving or even stimulating the growth of beneficial bacteria. Continued research is required before solid, evidence-based recommendations can be made.