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Previous analysis of Phase 3 clinical trial data for colorectal cancer patients treated with cetuximab revealed that patients harboring a KRAS mutation did not benefit from treatment. This finding set the stage for one of the first examples of cancer personalized medicine. Confusingly, patients with a Glycine to Aspartic Acid mutation at amino acid 13 of KRAS (KRASG13D) appeared to respond positively to cetuximab, suggesting this mutation is an exception to the rule that KRAS mutations confer resistance to Epidermal Growth Factor Receptor (EGFR) inhibitors. Oncologists have stated that the mechanism that explains why the KRASG13D mutation is an exception should be identified before KRASG13D colorectal cancer patients should be treated differently. We have recently elucidated this mechanism using mathematical modeling of the KRAS biochemical system coupled with experimental biology. The mechanism we revealed involves a cetuximab-mediated reduction in HRAS and NRAS signaling within KRASG13D cancer cells, owing to impaired binding of KRASG13D to the tumor suppressor, Neurofibromin (NF1). © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Lipid and cholesterol reprogramming are often observed in specific cancer subtypes. We find that triple-negative breast cancers (TNBCs), but not estrogen receptor-positive (ER+) ones, adopt nuclear receptor RAR-related orphan receptor γ (RORγ) as their new master activator of cholesterol biosynthesis program. Its dominant role over sterol regulatory element-binding protein 2 (SREBP2) renders TNBC highly vulnerable to RORγ inhibitors alone or in combination with statins. © 2020 Taylor & Francis Group, LLC.Accumulation of DNA damage in resting cells is an emerging cause of human disease. We identified a mechanism of DNA double-strand break (DSB) formation in non-replicating cells, which strictly depends on transcription. These transcriptional DSBs arise from the twinned processing of R-loops and topoisomerase I and may underlie neurological disorders and cancers. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC."In the field of observation, chance favours only the prepared mind" (Louis Pasteur). This motto seems to have guided our unexpected results published recently in Nature Communications, where we describe an epigenetic rheostat that regulates expression of the constituents of the lysosomal and autophagic systems. © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Normal cells exposed to cancer-causing events respond by triggering cellular senescence, a stress response which halts cell proliferation and constitutes a protective anti-cancer barrier. All-trans Retinoic Acid We have uncovered a previously unknown signaling pathway implicating p21-activated kinase 4 (PAK4) in the control of senescence in breast cancer, via the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit RELB and the CCAAT-enhancer-binding protein beta (C/EBPβ). © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.Chromatin remodeling is at the root of any cell fate decision, laying the foundation for the necessary reprogramming to occur. Our work shows histone H3 variants as a new addition to the ever-growing body of epigenetic regulators, one that is essential for cell fate transitions in carcinoma cells to promote tumor progression and metastasis. © 2020 Taylor & Francis Group, LLC.Reconstruction of combined skin and tendon loss in an injury of the dorsum of the hand is a challenging problem because it is required to achieve adequate excursion of the tendon. We herein report our case of extensor tendon repair for a dorsal hand injury using a rolled deep temporal fascial (DTF) graft and a free temporoparietal fascial flap. The patient regained satisfactory hand function with minimal donor site morbidity. DTF utilization as tendon grafts spares another incision for tendon grafting. Furthermore, one can integrate all the donor sites into the temporal region by choosing the scalp as a donor site for skin grafting. Patients can benefit from this procedure, which provides a functional reconstruction of the hand and leaves only inconspicuous donor site scars. © 2020 The Authors.Dermatographism, also known as skin writing, is an immunological response that remains an enigma. It occurs when normal skin is stroked with a dull object causing it to become raised and inflamed, and assume the shape of the stroke. Here we present a case of dermatographia in a denervated deep inferior epigastric perforator flap used to reconstruct breast tissue following mastectomy. © 2019 The Authors.Perforator-based flaps have in recent years become the mainstay of autologous breast reconstruction practice. Imaging modalities ranging from Doppler ultrasound to CT angiography demonstrate varying utility in the preoperative identification and localisation of perforators. Despite these available radiological investigations, finding and quantitatively assessing perforators remain a time-consuming and tedious process that is often complicated by a number of factors including variable anatomy prior surgery and body habitus. link2 Thermographic imaging shows promise as a novel modality for preoperative localisation of perforator vessels. This review summarises the currently available evidence for its application in perforator mapping for abdominal-based autologous breast reconstruction. We discuss the development of the technology over the years, its current use, its advantages and how it may impact on reconstructive breast surgery. © 2020 The Authors. Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.Background Breast surgery often requires changing the diameter of the areola. Recommended areolar size is commonly based on population averages, or surgical judgement. An ideal areola size has not been previously been described. We hypothesized that the ideal areolar diameter would be proportional to two breast measurements not commonly altered during breast surgery the nipple diameter and breast base width. Methods 'The Sun' newspaper (London, UK) publishes photographs of topless models which are selected based on the aesthetic appeal of their non-operated breasts. The publication's archive, from March 2014 to January 2017, was independently reviewed by three authors to identify photographs that presented a clear anterior view of the breast. The base width, nipple diameter and areolar diameter were measured independently by each reviewer. Measurements were pooled, and the mean was included for analysis. Ratios of the areolar diameter to the base width and the nipple diameter were calculated. Results The photographs of 58 models were eligible for inclusion. The average areolar diameter to base width was 0.29 (SD = 0.05). The average nipple to areolar diameter was 0.29 (SD = 0.06). Conclusions In aesthetically pleasing breasts, the areolar diameter is proportional to both the breast base width and nipple diameter. Breast base width is commonly measured preoperatively in aesthetic breast procedures, and is not typically modified. Breast base width can therefore be used to determine the ideal areolar size using the ratio of areolabase width ratio of 0.29 identified in this study. © 2019 The Authors. Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.Nipple sparing mastectomy with free tissue transfer for breast reconstruction offers excellent aesthetic outcomes but poses a challenge in monitoring the buried flap. Venous anastomotic flow couplers directly monitor buried flaps without the need for monitoring skin paddles. In a two year period we used the Synovis GEM™ flow coupler on 24 DIEP flaps. In our practice, flow couplers are effective in monitoring buried free flaps for breast reconstruction. The avoidance of a second procedure to remove a skin paddle improves patient experience and nullifies the additional flow coupler cost. link3 One patient needed return to theatre when a Doppler wire became dislodged early in the series. There were no other issues with flap monitoring and no flap failures. We offer our tips to optimise flow coupler use. Crown Copyright © 2020 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.We report a unique case of a digital tourniquet in a patient with ichthyosis vulgaris. We have identified no previous case reports documenting the occurrence of a digital tourniquet in patients caused by this condition. Ichthyosis vulgaris is a skin condition which causes increased scaling of the skin and in this case, resulted in the formation of a tourniquet-like circumferential constriction to one of the patient's digits. © 2019 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.In 2013 Clinical Commissioning Groups (CCGs) were created and became responsible for the planning and commissioning of health care services in their area. The Royal College of Surgeons and the British Association of Plastic, Reconstructive and Aesthetic Surgeons created guideline for the CCGs in 2013 for the surgical treatment of prominent ears. By looking at each of the CCGs' websites, we aim to review their equity and how well they adhere to standards to determine whether there is a regional variation for funding of this procedure. We found that 47% of the CCGs will fund this procedure only on an exceptionality basis, compared to 26% who had set criteria and would allow funding if these criteria were met. There was significant variation in the age at which funding would be considered with some CCGs allowing funding from 5 years of age and others not providing it until as old as 11 years. Only 11 policies made any reference to cartilage moulding and only 3 mentioned funding to allow correct fitting of hearing aids. Unfortunately, despite recommendations from the Royal College of Surgeons and the British Association of Plastic and Reconstructive Surgery, there is still variation in funding criteria between CCGs for correction of prominent ear surgery. This may result in patients being treated differently depending on their postcode. We would urge commissioners to apply more consistent and uniform guidelines for the funding of surgical correction of prominent ears. © 2019 Published by Elsevier Ltd on behalf of British Association of Plastic, Reconstructive and Aesthetic Surgeons.Purpose Carpal tunnel release, one of the most commonly performed procedures in Veterans Affairs (VA) medical centers, is often performed under local anesthesia alone. In this patient population, there is an increased prevalence of psychiatric disorders. Our hypothesis is that there is no difference in operating time, request for sedation, or complications in the veteran population with or without a recognized psychiatric history. Methods A retrospective cohort study was performed at a VA medical center from January 2013 to January 2017 by the senior surgeon (E.S.L). Patients were divided into two groups patients with no known psychiatric history (n = =33) and patients with an active psychiatric diagnosis (n = =25), including post-traumatic stress disorder, anxiety disorder, bipolar disorder, depression, substance abuse, or panic disorder. Primary endpoints included operation time, time in operating room, request for sedation, and complication rates. Results Fifty-nine percent of patients successfully underwent wide-awake hand surgery, while 41% requested sedation.