Metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

OBJECTIVES: The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer. MATERIAL AND METHODS: Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35mg) in 1mL olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4mg/kg and 2mg/kg), Met (200mg/kg) alone and in combination with Dox (4mg/kg). Met pre-treated DMBA control groups received Dox 4mg/kg and 2mg/kg. RESULTS: Met pre-treated groups treated with Dox exhibited a decrease in tumor incidence, tumor volume and increased survival rate than the DMBA group. Organ-to-body weight ratios and histopathology of heart, liver and lungs of Met pre-treated groups treated with Dox showed lesser toxicity than Dox treated DMBA control groups. There was a noteworthy decrease in malondialdehyde levels and a substantial increase in the levels of reduced glutathione together with a significant decrease in the levels of inflammatory markers like IL-6, IL-1ß and NF-κB in Met pre-treated groups treated with Dox. Histopathology of breast tumors revealed better control of tumors in Met pre-treated groups treated with Dox than DMBA control group. Immunohistochemistry and real-time PCR data revealed a significant reduction in Ki67 expression in Met pre-treated groups treated with Dox as compared to the DMBA control group. CONCLUSION: The present study suggests that metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

Prediction of visual function from automatically quantified optical coherence tomography biomarkers in patients with geographic atrophy using machine learning.

Geographic atrophy (GA) is a vision-threatening manifestation of age-related macular degeneration (AMD), one of the leading causes of blindness globally. Objective, rapid, reliable, and scalable quantification of GA from optical coherence tomography (OCT) retinal scans is necessary for disease monitoring, prognostic research, and clinical endpoints for therapy development. Such automatically quantified biomarkers on OCT are likely to further elucidate structure-function correlation in GA and thus the pathophysiological mechanisms of disease development and progression. In this work, we aimed to predict visual function with machine-learning applied to automatically acquired quantitative imaging biomarkers in GA. A post-hoc analysis of data from a clinical trial and routine clinical care was conducted. A deep-learning automated segmentation model was applied on OCT scans from 476 eyes (325 patients) with GA. A separate machine learning prediction model (Random Forest) used the resultant quantitative OCT (qOCT) biomarkers to predict cross-sectional visual acuity under standard (VA) and low luminance (LLVA). The primary outcome was regression coefficient (r2) and mean absolute error (MAE) for cross-sectional VA and LLVA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. OCT parameters were predictive of VA (r2 0.40 MAE 11.7 ETDRS letters) and LLVA (r2 0.25 MAE 12.1). Normalised random forest feature importance, as a measure of the predictive value of the three constituent features of GA; retinal pigment epithelium (RPE)-loss, photoreceptor degeneration (PDR), hypertransmission and their locations, was reported both on voxel-level heatmaps and ETDRS-grid subfields. The foveal region (46.5%) and RPE-loss (31.1%) had greatest predictive importance for VA. For LLVA, however, non-foveal regions (74.5%) and PDR (38.9%) were most important. In conclusion, automated qOCT biomarkers demonstrate predictive significance for VA and LLVA in GA. LLVA is itself predictive of GA progression, implying that the predictive qOCT biomarkers provided by our model are also prognostic.

Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents.

Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

Winter Deployment 14 and 15: an audit of injury and illness rates in an Arctic environment.

INTRODUCTION: Arduous military training in a cold weather environment is likely to lead to a variety of injuries to the population at risk (PAR). This paper examines injury rates and medical presentations over the two years of Winter Deployments in 2014 and 2015 (WD14 and WD15) and proposes recommendations for future WDs. METHODS: Data on injury rates, number of aeromedical evacuations, and number of days of restricted duties allocated were collected prospectively for all patients presenting to Asegarden Medical Centre, Norway, during WD14 and WD15. The data were calculated as a percentage of the total PAR on each deployment to allow meaningful comparison. RESULTS: During WD14, 22.8% of the PAR presented to the Medical Centre compared to 26.9% during WD15. WD15 saw a reduction in the presentation of musculoskeletal (MSK) injuries, cold weather (CW) injuries and burns. Skin problems and diarrhoea and vomiting (D&V) remained similar in both years. An increase in dental and other presentations was seen in WD15. A reduction in the overall aeromedical evacuations and number of patients requiring a light duties (LD) chit was seen during WD15. CONCLUSION: WD15 has seen a decrease in injury rates, the number of aeromedical evacuations and LD chits issued. It is difficult to know whether these changes are a result of improved medical support, training or equipment. The liaison between the command, medical and training elements has led to improvements and should now concentrate on ways to further reduce injury rates whilst maximising arduous training benefits in an Arctic environment.

Measures of socioeconomic status and self-reported glaucoma in the U.K. Biobank cohort.

PURPOSE: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the U.K. Biobank. METHODS: Biobank is a study of U.K. residents aged 40-69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112,690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined. RESULTS: In all, 1916 (1.7%) people in U.K. Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs. 56.7 years, P<0.001) and male (2.1% vs. 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was -0.72 for those reporting glaucoma and -0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18,000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect. CONCLUSIONS: In a large U.K. cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions.

Aflibercept in wet AMD beyond the first year of treatment: recommendations by an expert roundtable panel.

This paper provides expert recommendations on administration of aflibercept in wet age-related macular degeneration (AMD) after Year 1 (Y1), based on a roundtable discussion held in London, UK in November 2014. The goals of treatment after Y1 are to maintain visual and anatomical gains whilst minimising treatment burden and using resources effectively. The treatment decision should be made at the seventh injection visit (assuming the label has been followed) in Y1, and three approaches are proposed: (a) eyes with active disease on imaging/examination but with stable visual acuity (VA) at the end of Y1 should continue with fixed 8-weekly dosing; (b) eyes with inactive disease on imaging/examination and stable VA should be managed using a 'treat and extend' (T&E) regimen. T&E involves treating and then extending the interval until the next treatment, by 2-week intervals, to a maximum of 12 weeks, provided the disease remains inactive. If there is new evidence of disease activity, treatment is administered and the interval to the next treatment shortened; and (c) if there has been no disease activity for ≥3 consecutive visits, a trial of monitoring without treatment may be appropriate, initiated at the end of Y1 or at any time during Y2. Where possible, VA testing, OCT imaging and injection should be performed at the same visit. The second eye should be monitored to detect fellow eye involvement. In bilateral disease, the re-treatment interval should be driven by the better-seeing eye or, if the VA is similar, the eye with the more active disease.

Certifications for sight impairment due to age related macular degeneration in England.

OBJECTIVES: To examine variability across England in certification rates for age related macular degeneration (AMD) between 1st April 2011 and 31st March 2012. STUDY DESIGN: Cross-sectional survey. METHODS: An electronic version of the CVI, the ECVI, was used at the Certifications Office, London, to transfer information from paper based certificates into a database. The electronic certifications data set was queried for all certificates completed in England between April 1st 2011 and March 31st 2012 with the main cause of certifiable visual loss being AMD or with the main cause of certifiable visual loss being multiple pathology but a contributory cause being AMD. Data were explored by type of AMD, visual status, age and sex and then directly standardized rates were computed by English region. RESULTS: The Certifications Office received 23,616 CVIs for England between April 2011 and March 2012, of which 10,481 (44%) were people certified severely sight-impaired (blind) (SSI) and 12,689 (54%) were certified as sight-impaired (partial sight) (SI). The remainder did not have visual status classified. AMD contributed to 11546 causes of certification on the CVI forms during this period, 53% of forms being for geographic atrophy (GA)/dry AMD which is currently mostly untreatable. The median (interquartile) age at certification for AMD was 86 (81, 90) years and women were more commonly certified than men (66%). Considerable variability was seen across English regions, although there was consistency in that GA was the more common form in all areas. CONCLUSIONS: There is considerable regional variability in CVI rates in England, which are not attributable to differences in age or sex. Reasons for such variability need examination yet this should not undermine the value of these data in terms of describing those newly registered with sight impairment due to AMD who are predominantly female and over 85 years of age.

Characteristics of the positive ion source at reduced gas feed.

The neutral beam injector of steady state superconducting tokamak (SST1-NBI) at IPR is designed for injecting upto 1.7 MW of neutral beam (Hº, 30-55 keV) power to the tokamak plasma for heating and current drive. Operations of the positive ion source (PINI or Plug-In-Neutral-Injector) of SST1-NBI were carried out on the NBI test stand. The PINI was operated at reduced gas feed rate of 2-3 Torr l/s, without using the high speed cryo pumps. Experiments were conducted to achieve a stable beam extraction by optimizing operational parameters namely, the arc current (120-300 A), acceleration voltage (16-40 kV), and a suitable control sequence. The beam divergence, power density profiles, and species fractions (H(+):H2(+):H3(+)) were measured by using the diagnostics such as thermal calorimetry, infrared thermography, and Doppler shift spectroscopy. The maximum extracted beam current was about 18 A. A further increase of beam current was found to be limited by the amount of gas feed rate to the ion source.

How many people in England and Wales are registered partially sighted or blind because of age-related macular degeneration?

PURPOSE: The purpose of the study was to determine what proportion of new certifications between 1 April 2007 and 31 March 2008 could be attributed to age-related macular degeneration (AMD) and to describe the AMD-certified population in England and Wales. METHODS: An electronic version of the Certificate of Vision Impairment form (CVI), the ECVI, was used at the certifications office to transfer information from the paper-based certificates into a database. The electronic certifications data set was queried for all certificates completed between 1 April 2007 and 31 March 2008 with the main cause of certifiable visual loss being AMD or with the main cause of certifiable visual loss being multiple pathology but a contributory cause being AMD. The electronic data set was adapted so that a distinction could be made between geographic atrophy (GA) and neovascular AMD (nAMD). RESULTS: The Certifications Office received 23 185 CVIs between April 2007 and March 2008, of whom 9823 (42%) were people registered severely sight impaired (SSI) and 12 607 (52%) were certified as sight impaired (SI). AMD contributed to 13 000 causes of registration on the CVI forms during this period and was the main cause in 11 015 people. In these 11 015 people, GA accounted for 49.3%, nAMD 35.1%, and AMD not specified 15.7%. CONCLUSIONS: The data in this report provide detailed information on CVI registration due to AMD before the widespread adoption of ranibizumab therapy in NHS practice and provide an insight into the burden of vision loss due to AMD at a time of great change in the management of nAMD.

Ciliated hepatic cyst leading to squamous cell carcinoma of the liver - A case report and review of the literature.

INTRODUCTION: Ciliated hepatic foregut cysts (CHFC) are rare, typically benign liver lesions. Primary squamous cell carcinoma (SCC) of the liver is also a rare entity with only approximately 25 reported cases in the literature. Recently, there have been four reports of malignant transformation of CHFC into primary squamous cell carcinoma of the liver. Here we report a fifth with unique presentation and review the literature. PRESENTATION OF CASE: A 34 year-old man, with a history of ulcerative colitis, was incidentally found to have a 10cm lesion in the right anterior sector plus left medial section of the liver on computerized tomography (CT) scan. The patient was asymptomatic at presentation and neoplastic markers were not elevated. Sequential transarterial chemoembolization (TACE) and portal vein embolization (PVE) allowed for left lateral section plus segment 1 hypertrophy and subsequent resection. Histology later revealed the cyst to be a CHFC and showed its malignant transformation. At 6 month follow-up, the patient has lung and abdominal recurrence. DISCUSSION: With now the fifth case of malignant transformation of CHFC being reported, approximately 5% of all reported CHFC have undergone malignant transformation. This frequency, taken together with the aggressive disease course and poor prognosis, suggests that CHFC must not be presumed benign and should be regarded with clinical suspicion. CONCLUSION: Accurate diagnosis of CHFC is mandatory given its potential malignant transformation. Even in asymptomatic CHFC, surgical excision is recommended. In addition, in cases of otherwise unresectable lesions, sequential TACE and PVE may provide optimal hypertrophy of future liver remnant.

Ranibizumab for the treatment of choroidal neovascularisation secondary to pathological myopia: interim analysis of the REPAIR study.

AIMS: To evaluate the efficacy and safety of intravitreal ranibizumab in patients with choroidal neovascularisation secondary to pathological myopia (myopic CNV). Data are from a pre-planned, 6-month interim analysis. METHODS: Phase II, open-label, single arm, multicentre, 12-month study, recruiting patients (aged ≥18 years) with active primary or recurrent subfoveal or juxtafoveal myopic CNV, with a best-corrected visual acuity (BCVA) score of 24-78 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in the study eye and a diagnosis of high myopia of at least -6 dioptres. Patients received 0.5 mg ranibizumab administered intravitreally to the study eye, followed by monthly injections given as needed (based on a predefined algorithm) for up to 11 months. RESULTS: At 6 months, mean BCVA improved from baseline by 12.2 letters, as did central macular thickness (in this interim analysis defined as a measure of either central subfield macular thickness or centre point macular thickness) from baseline by 108 µm in the 48 study eyes of 48 patients. Fewer patients had centre-involving intraretinal oedema (13.0% vs 91.5%), intraretinal cysts (10.9% vs 57.4%), or subretinal fluid (13.0% vs 66.0%) at 6 months than at baseline. Patients received a mean of 1.9 retreatments, were satisfied with ranibizumab treatment, and well being was maintained. No new safety signals were identified. CONCLUSIONS: Results from the planned interim analysis support the role of ranibizumab in the treatment of myopic CNV, with excellent efficacy achieved with a low number of injections and few serious adverse events.

Age-related macular degeneration: diagnosis and management.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blind registration in Western Europe and the third leading cause of blindness worldwide. METHODS: The management of AMD is discussed with a review of current and new treatments. RESULTS: Although there is no treatment for advanced dry AMD (geographic atrophy), there have been considerable advances in the management of neovascular AMD (nAMD). Established therapies for nAMD include laser photocoagulation and photodynamic therapy (PDT), but these have largely been superseded by agents which block the action of vascular endothelial growth factor (anti-VEGF agents). Current preventative strategies involve cessation of smoking and use of specific nutritional supplements to reduce the risk of developing nAMD. CONCLUSIONS: There have been exciting advances in the treatment of nAMD and increased understanding of the genetics and pathogenic mechanisms involved will hopefully lead to the development of new therapies in the future.

Intravitreal triamcinolone acetonide for macular oedema owing to retinal vein occlusion.

PURPOSE: To assess the long-term safety and efficacy of intravitreal triamcinolone acetonide injection in the management of macular oedema caused by central, hemi-, and branch retinal vein occlusion (CRVO, HRVO, or BRVO). METHODS: This prospective, interventional case series included 13 patients (13 eyes) with retinal vein occlusion and macular oedema. They received an intravitreal injection of 4 mg triamcinolone acetonide. Follow-up was for 1 year with repeat injections where appropriate. Outcome measures were visual acuity and macular thickness measured using ocular coherence tomography (OCT). RESULTS: There were four patients with CRVO, one with HRVO, and eight with BRVO (13 eyes). Mean duration of symptoms before intravitreal triamcinolone acetonide injection was 6.8 months (SD 4.5 months). Eight eyes (62%) responded well with improved visual acuity and macular thickness 1-3 months postinjection. All eight eyes developed recurrent macular oedema and five received repeat injections. Three patients declined a second injection. No improvement in visual acuity or OCT macular thickness was seen after the second injection with visual acuity returning to baseline levels at 1-year follow-up. Three eyes (23%) showed no response to the initial injection (no improvement in macular thickness or visual acuity). Seven patients (54%) had a rise in intraocular pressure with six (46%) requiring treatment. CONCLUSIONS: Intravitreal injection of triamcinolone acetonide is effective as a short-term treatment of macular oedema owing to retinal vein occlusion, improving both visual acuity and macular thickness. However, this effectiveness is not maintained after 1 year despite repeat injections.

Spontaneous thoracic duct cyst.

Spontaneous and asymptomatic supraclavicular thoracic duct cysts (lymphoceles ) are rare. Only five cases have been reported so far. They are more common after surgery or trauma and have been reported in the abdomen, mediastinum, pelvis and neck. They must be differentiated from other neck cysts as failure to recognise their attachment may result in the disastrous consequence of chylothorax. A high index of suspicion is necessary, and diagnosis usually can be established by fine-needle aspiration and suitable imaging. This case is reported along with a review of the literature and management options, including that of inadvertent damage to the thoracic duct.

Sarcoidosis.

UNLABELLED: Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin. The cutaneous manifestations of sarcoidosis often enable the dermatologist to be the first physician to make the diagnosis. This article reviews essential sarcoidosis pathophysiology, clinical polymorphisms, systemic evaluation, and treatment modalities for cutaneous sarcoidosis to further enhance the dermatologist's understanding of this disease entity. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the theories of the pathogenesis of sarcoidosis, its cutaneous manifestations, its various syndromes and associations, and its presentation in children. Participants should also be more knowledgeable about diagnostic evaluation, measurement of disease progression, treatment modalities, and the prognosis and mortality data of sarcoidosis.

Long-term survival after ablation of the atrioventricular node and implantation of a permanent pacemaker in patients with atrial fibrillation.

BACKGROUND: In patients with atrial fibrillation that is refractory to drug therapy, radio-frequency ablation of the atrioventricular node and implantation of a permanent pacemaker are an alternative therapeutic approach. The effect of this procedure on long-term survival is unknown. METHOD: We studied all patients who underwent ablation of the atrioventricular node and implantation of a permanent pacemaker at the Mayo Clinic between 1990 and 1998. Observed survival was compared with the survival rates in two control populations: age- and sex-matched members of the Minnesota population between 1970 and 1990 and consecutive patients with atrial fibrillation who received drug therapy in 1993. RESULTS: A total of 350 patients (mean [+/-SD] age, 68+/-11 years) were studied. During a mean of 36+/-26 months of follow-up, 78 patients died. The observed survival rate was significantly lower than the expected survival rate based on the general Minnesota population (P<0.001). Previous myocardial infarction (P<0.001), a history of congestive heart failure (P=0.02), and treatment with cardiac drugs after ablation (P=0.03) were independent predictors of death. Observed survival among patients without these three risk factors was similar to expected survival (P=0.43). None of the 26 patients with lone atrial fibrillation died during follow-up (37+/-27 months). The observed survival rate among patients who underwent ablation was similar to that among 229 controls with atrial fibrillation (mean age, 67+/-12 years) who received drug therapy (P=0.44). CONCLUSIONS: In the absence of underlying heart disease, survival among patients with atrial fibrillation after ablation of the atrioventricular node is similar to expected survival in the general population. Long-term survival is similar for patients with atrial fibrillation, whether they receive ablation or drug therapy. Control of the ventricular rate by ablation of the atrioventricular node and permanent pacing does not adversely affect long-term survival.

Necrotizing fasciitis caused by Aeromonas hydrophila.

Aeromonas Hydrophila is a gram-negative bacillus commonly found in soil, sewage, and fresh or brackish water in many parts of the United States. In healthy people, the most common clinical manifestations attributed to Aeromonas are diarrhea and soft tissue infections. In people with suppressed immune systems or liver disease, A hydrophila can cause meningitis, endocarditis, peritonitis, hemolytic-uremic syndrome, or septicemia. We present the first known case of fulminant necrotizing fasciitis from A hydrophila that is not associated with trauma, liver disease, or immunosuppression.

Metastatic endometrial carcinoma of the neck.

We report a case of metastatic endometrial carcinoma of the neck. A patient with a past medical history of squamous cell carcinoma of the larynx, breast carcinoma and endometrial carcinoma presented with a neck mass. Fine needle aspiration cytology (FNAC) showed this to be a poorly differentiated carcinoma with squamoid features and thus a potentially curative neck dissection was performed. Histology of the mass showed a clear cell endometrial carcinoma. Metastatic gynacecological malignancies to the head and neck are rare and this is the first reported case of metastatic endometrial carcinoma in the neck.

Pharyngeal pouch surgery: a five year review.

The treatment of pharyngeal pouch varies widely. Our aim was to establish current and recent practice in pharyngeal pouch surgery in our department and set guidelines for future management. A retrospective audit over a 5-year period was performed with all data derived from patient notes. 28 procedures were performed on 24 patients with a mean age of 72 years. Over two thirds of these patients (68%) underwent an endoscopic procedure (stapling or diathermy) and the remainder underwent excision (14%), inversion (10%), cricopharyngeal myotomy (4%) or dilatation (4%). The primary diagnostic investigation performed was a barium swallow in 17 cases, but in 7 cases, referred by gastroenterologists, an oesophagogastroscopy was performed despite characteristic presenting features in all cases. The average inpatient stay was similar for endoscopic and excision procedures (5.5 and 5 days respectively), but longer for inversion procedures (9 days). This was influenced mainly by operative complications. 2 endoscopic stapling procedures were complicated by perforations and 1 patient developed hoarseness after an inversion procedure. The mean follow up time was one month at which stage all asymptomatic patients were discharged. 2 patients treated by endoscopic stapling and 1 patient treated by inversion complained of persistent symptoms and required further surgery. We conclude that endoscopic stapling was the commonest procedure used. Concerning future management, the use of nasogastric tubes after uncomplicated stapling procedures was abandoned. Also it was felt that large pouches should be treated by excision, small pouches by cricopharyngeal myotomy and the remainder by endoscopic stapling. The long-term evaluation of results was also deemed necessary.

Neutrophil chemokine production in the skin following scald injury.

The present study was conducted to determine whether local production of neutrophil chemoattractant cytokines preceded the influx of neutrophils following dermal scald injury. To accomplish this, dermal tissue was examined for inflammatory infiltrate and the level of KC, a murine homolog of human interleukin-8, at various time points after scald injury. The studies reveal that there was a largely neutrophilic infiltrate at 1 day post-injury which persisted for 4 days. Dermal KC levels increased significantly at 4 h, returned to baseline at 8 h and were elevated again from 1 to 3 days post-burn (P < 0.01). At 3 days post-burn, KC was elevated 15-fold above the level in sham treated mice (P < 0.01). These observations demonstrate that the influx of neutrophils into the skin follows the expression of KC in the skin. This suggests that it should be possible to alter neutrophil accumulation at the wound site by manipulating the local chemokine signal.