Do wounds really heal faster if they happen during the daytime? A new study out this week claims that wounds that occur at night take 60 percent longer to heal than those sustained during the day. I disagree with this interpretation. A study conducted by Nathaniel P. Hoyle, Ph.D. — from the MRC Laboratory of Molecular Biology in Cambridge in the United Kingdom — and his colleagues and published on Wednesday in the journal Science Translational Medicine reports that some of the cells resident in our skin are under the influence of circadian rhythms. As part of the work, the team analyzed data from the International Burn Injury Database to see whether or not the same applies to healing times in human burns. They report that in a subset of burn cases, those sustained between 8 p.m. and 8 a.m. took 60 percent longer to heal than burns that occurred between 8 a.m and 8 p.m. The story has been picked up by other news outlets, but I think these claims are unsubstantiated and misleading. Here is why. Burn patient data Dr. Hoyle and his colleagues used data from major burn units in England and Wales from 2012 to 2015. The inclusion criteria were people aged 18 to 60 with a body mass index (BMI) between 20 and 30, who had been admitted to the emergency room because of their burn injury. Data from patients with any previous diseases or those who had received a skin graft were excluded. In this subset of patients, Dr. Hoyle found a significant difference in the time it took for 95 percent of each burn to heal when he compared 75 daytime burns with 43 night-time ones. "We observed an about 60 percent decrease in healing time when burns occurred during the night compared with during the day," he writes in the paper. Senior study author John O'Neill, Ph.D., comments on the significance of the findings in a press release. "It may be," he says, "that healing time could be improved by resetting the cells' clocks prior to surgery, perhaps by applying drugs that can reset the biological clock to the time of best healing in the operation site." The main issue is that burns occur in individuals of all ages, all sizes, and those with underlying conditions. The burns themselves also come in all different shapes and sizes, and there are no data here to indicate the size of each burn. But size matters when it comes to wound healing times. The other problem is the exclusion of burns that received skin grafts. Deep vs. superficial burns Skin grafts are used when a burn is not likely to heal by itself. This is the case for deep burns and large burns. I asked Dr. Hoyle why he and his team decided to leave out data from patients with skin grafts. He said, "[W]e excluded skin grafts because it would affect how well the wound heals dramatically and we wanted the burns to have been treated, more or less, in the similar way. Including both grafted and ungrafted wounds would have massively increased variability." Here is the crux of the problem: by looking at a subset of the available data, it is impossible to make a sweeping statement about burns or wounds in general. I spoke to Dr. Baljit Dheansa — who is Lead Surgeon for Burns at Queen Victoria Hospital in East Grinstead in the U.K. — about the study. In his opinion, "ome of the data relating to burns in humans is not detailed enough to make any conclusion, as the variation in burn size or depth is too great [...] we cannot say if we really are comparing like with like. "I advise caution in interpreting such data and suggest that much more detailed analysis is performed before making any conclusions," he added. So, what exactly did the study find, and what are the implications on wound healing? Cell behavior influenced by circadian clock The fact that fibroblasts — or the main cell type in the dermis, the deeper layer in our skin — are influenced by circadian rhythms is not new. The big question is whether or not this control is exerted by the cells themselves, and how this affects their behavior. Dr. Hoyle and colleagues therefore started with a proteomics screen, using fibroblasts from mice genetically engineered to carry reporters for the circadian clock. This allowed the researchers to synchronize the cells to a 24-hour rhythm. The results showed that actin dynamics were under the control of the circadian clock. Actin is a key component of the cytoskeleton, which maintains a cell's structural integrity. Actin is also essential for cell movement, which, in turn, is essential for wound healing. Dr. Hoyle summarized the team's approach, saying, "Our work built up from molecular biological foundations — a hypothesis-free proteomics screen in fibroblasts." "So incrementally we could make clear predictions at each step as we moved up the complexity scale. First, actin would be rhythmic due to rhythmic actin regulator abundance, second that cells would therefore have rhythmic motility, and finally that wound healing would be rhythmic." Source
