Robust rapid-setting antibacterial liquid bandages

Abstract: Bandaging is a steadfast but time-consuming component of wound care with limited technical advancements to date. Bandages must be changed and infection risk managed. Rapid-set liquid bandages are efficient alternatives but lack durability or inherent infection control. We show here that antibacterial zinc (Zn) and copper (Cu) species greatly enhance the barrier properties of the natural, waterproof, bio-adhesive polymer, shellac. The material demonstrated marked antibacterial contact properties and, in ex-vivo studies, effectively locked-in pre-applied therapeutics. When challenged in vivo with the polybacterial bovine wound infection ‘digital dermatitis’, Zn/Cu-shellac adhered rapidly and robustly over pre-applied antibiotic. The bandage self-degraded, appropriately, over 7 days despite extreme conditions (faecal slurry). Treatment was well-tolerated and clinical improvement was observed in animal mobility. This new class of bandage has promise for challenging topical situations in humans and other animals, especially away from controlled, sterile clinical settings where wounds urgently require protection from environmental and bacterial contamination

The mechanisms by which polyamines accelerate tumor spread

Increased polyamine concentrations in the blood and urine of cancer patients reflect the enhanced levels of polyamine synthesis in cancer tissues arising from increased activity of enzymes responsible for polyamine synthesis. In addition to their de novo polyamine synthesis, cells can take up polyamines from extracellular sources, such as cancer tissues, food, and intestinal microbiota. Because polyamines are indispensable for cell growth, increased polyamine availability enhances cell growth. However, the malignant potential of cancer is determined by its capability to invade to surrounding tissues and metastasize to distant organs. The mechanisms by which increased polyamine levels enhance the malignant potential of cancer cells and decrease anti-tumor immunity are reviewed. Cancer cells with a greater capability to synthesize polyamines are associated with increased production of proteinases, such as serine proteinase, matrix metalloproteinases, cathepsins, and plasminogen activator, which can degrade surrounding tissues. Although cancer tissues produce vascular growth factors, their deregulated growth induces hypoxia, which in turn enhances polyamine uptake by cancer cells to further augment cell migration and suppress CD44 expression. Increased polyamine uptake by immune cells also results in reduced cytokine production needed for anti-tumor activities and decreases expression of adhesion molecules involved in anti-tumor immunity, such as CD11a and CD56. Immune cells in an environment with increased polyamine levels lose anti-tumor immune functions, such as lymphokine activated killer activities. Recent investigations revealed that increased polyamine availability enhances the capability of cancer cells to invade and metastasize to new tissues while diminishing immune cells' anti-tumor immune functions

Physiological response of the retinal pigmented epithelium to 3-ns pulse laser application, in vitro and in vivo

BACKGROUND: To treat healthy retinal pigmented epithelium (RPE) with the 3-ns retinal rejuvenation therapy (2RT) laser and to investigate the subsequent wound-healing response of these cells. METHODS: Primary rat RPE cells were treated with the 2RT laser at a range of energy settings. Treated cells were fixed up to 7 days post-irradiation and assessed for expression of proteins associated with wound-healing. For in vivo treatments, eyes of Dark Agouti rats were exposed to laser and tissues collected up to 7 days post-irradiation. Isolated wholemount RPE preparations were examined for structural and protein expression changes. RESULTS: Cultured RPE cells were ablated by 2RT laser in an energy-dependent manner. In all cases, the RPE cell layer repopulated completely within 7 days. Replenishment of RPE cells was associated with expression of the heat shock protein, Hsp27, the intermediate filament proteins, vimentin and nestin, and the cell cycle-associated protein, cyclin D1. Cellular tight junctions were lost in lased regions but re-expressed when cell replenishment was complete. In vivo, 2RT treatment gave rise to both an energy-dependent localised denudation of the RPE and the subsequent repopulation of lesion sites. Cell replenishment was associated with the increased expression of cyclin D1, vimentin and the heat shock proteins Hsp27 and αB-crystallin. CONCLUSIONS: The 2RT laser was able to target the RPE both in vitro and in vivo, causing debridement of the cells and the consequent stimulation of a wound-healing response leading to layer reformation.John P. M. Wood, Marzieh Tahmasebi, Robert J. Casson, Malcolm Plunkett, Glyn Chidlo

Induction chemotherapy followed by chemoradiotherapy versus chemoradiotherapy alone as neoadjuvant treatment for locally recurrent rectal cancer: study protocol of a multicentre, open-label, parallel-arms, randomized controlled study (PelvEx II)

Background A resection with clear margins (R0 resection) is the most important prognostic factor in patients with locally recurrent rectal cancer (LRRC). However, this is achieved in only 60 per cent of patients. The aim of this study is to investigate whether the addition of induction chemotherapy to neoadjuvant chemo(re)irradiation improves the R0 resection rate in LRRC. Methods This multicentre, international, open-label, phase III, parallel-arms study will enrol 364 patients with resectable LRRC after previous partial or total mesorectal resection without synchronous distant metastases or recent chemo- and/or radiotherapy treatment. Patients will be randomized to receive either induction chemotherapy (three 3-week cycles of CAPOX (capecitabine, oxaliplatin), four 2-week cycles of FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) or FOLFORI (5-fluorouracil, leucovorin, irinotecan)) followed by neoadjuvant chemoradiotherapy and surgery (experimental arm) or neoadjuvant chemoradiotherapy and surgery alone (control arm). Tumours will be restaged using MRI and, in the experimental arm, a further cycle of CAPOX or two cycles of FOLFOX/FOLFIRI will be administered before chemoradiotherapy in case of stable or responsive disease. The radiotherapy dose will be 25 × 2.0 Gy or 28 × 1.8 Gy in radiotherapy-naive patients, and 15 × 2.0 Gy in previously irradiated patients. The concomitant chemotherapy agent will be capecitabine administered twice daily at a dose of 825 mg/m2 on radiotherapy days. The primary endpoint of the study is the R0 resection rate. Secondary endpoints are long-term oncological outcomes, radiological and pathological response, toxicity, postoperative complications, costs, and quality of life. Discussion This trial protocol describes the PelvEx II study. PelvEx II, designed as a multicentre, open-label, phase III, parallel-arms study, is the first randomized study to compare induction chemotherapy followed by neoadjuvant chemo(re)irradiation and surgery with neoadjuvant chemo(re)irradiation and surgery alone in patients with locally recurrent rectal cancer, with the aim of improving the number of R0 resections

Facilitated early ileostomy closure after rectal cancer surgery: a case-matched study

BACKGROUND: The aim of this study was to evaluate the outcomes of an early stoma closure protocol facilitated by Seprafilm wrapping of defunctioning ileostomies compared with a similar group of patients with conventional stoma formation and closure. METHODS: Consecutive patients undergoing defunctioning ileostomy following rectal resection with pelvic anastomosis were planned for early closure and had their ileostomy wrapped in Seprafilm at the time of formation. Stoma closure was performed at 4-6 weeks if water-soluble contrast enema showed no evidence of leak, and the patient's physiological parameters had been optimized. Patients were matched for age, gender, American Society of Anaesthesiologists score, neoadjuvant treatment and procedure, with patients undergoing conventional ileostomy formation and closure. Outcomes were compared using the 2-tailed Mann-Whitney U test and Fisher's exact test. RESULTS: Following resection, twenty-two patients (69 %) were suitable for early closure and underwent stoma closure at a median of 37 days (range 25-90 days). Seprafilm-wrapped ileostomies were closed earlier than the conventional ileostomies (median 55 days (range 25-250 days) versus 213 days (range 86-352 days), p < 0.001). There was no difference between the groups as regards length of hospital stay or complications following ileostomy closure. Eighteen Seprafilm stoma patients and 22 conventional stoma patients received adjuvant chemotherapy. Median time to starting chemotherapy from resection was 10 versus 8.5 weeks, respectively (p = 0.36). CONCLUSIONS: An early stoma closure protocol facilitated by Seprafilm wrapping of the ileostomy is practical, does not increase morbidity and significantly reduces the time with a stoma for the patient. An early stoma closure protocol did not significantly delay in the commencement of chemotherapy

Warmed, humidified CO2 insufflation benefits intraoperative core temperature during laparoscopic surgery: A meta-analysis

BACKGROUND: Intraoperative hypothermia is linked to postoperative adverse events. The use of warmed, humidified CO2 to establish pneumoperitoneum during laparoscopy has been associated with reduced incidence of intraoperative hypothermia. However, the small number and variable quality of published studies have caused uncertainty about the potential benefit of this therapy. This meta-analysis was conducted to specifically evaluate the effects of warmed, humidified CO2 during laparoscopy. METHODS: An electronic database search identified randomized controlled trials performed on adults who underwent laparoscopic abdominal surgery under general anesthesia with either warmed, humidified CO2 or cold, dry CO2 . The main outcome measure of interest was change in intraoperative core body temperature. RESULTS: The database search identified 320 studies as potentially relevant, and of these, 13 met the inclusion criteria and were included in the analysis. During laparoscopic surgery, use of warmed, humidified CO2 is associated with a significant increase in intraoperative core temperature (mean temperature change, 0.3°C), when compared with cold, dry CO2 insufflation. CONCLUSION: Warmed, humidified CO2 insufflation during laparoscopic abdominal surgery has been demonstrated to improve intraoperative maintenance of normothermia when compared with cold, dry CO2

Modeling open surgery in mice to explore peritoneal damage, carbon dioxide humidification and desmoidogenesis

Background: The exposure of the peritoneum to desiccation during surgery generates lasting damage to the mesothelial lining which impacts inflammation and tissue repair. We have previously explored open abdominal surgery in mice subjected to passive airflow however, operating theatres employ active airflow. Therefore, we sought an engineering solution to recapitulate the active airflow in mice. Similarly, to the passive airflow studies we investigated the influence of humidified-warm carbon dioxide (CO2) on this damage in the context of active airflow. Additionally, we addressed the controversial role of surgery in exacerbating desmoidogenesis in a mouse model of familial adenomatous polyposis. Methods: An active airflow mouse-operating module manufactured to produce the equivalent downdraft airflow to that of a modern operating theatre was employed. We quantified mesothelial cell integrity by scanning electron microscopy (SEM) sampled from the peritoneal wall that was subjected to mechanical damage or not, with and without the delivery of humidified-warm CO2. To explore the role of open and laparoscopic surgery in the process of desmoidogenesis we crossed Apcmin/ + C57Bl/6 mice with p53 +/- mice to generate animals that developed desmoid tumors with 100% penetrance. Results: One hour of active airflow generates substantial damage to peritoneal mesothelial cells and their microvilli as measured at 24 h post intervention, which is significantly greater than that generated by passive airflow. Use of humidified-warm CO2 mostly protects the mesothelium that had not experienced additional mechanical (surgical) damage at 24 h. Maximal damage was evident in all treatment groups regardless of flow or use of gas. At day 10 mechanically-damaged peritoneum remains in mice but is essentially repaired in the gas-treated groups. Regarding desmoidogenesis, operating procedures did not increase the frequency of desmoid tumors but their frequency correlated with time following surgery but not age of mice. Conclusions: Active airflow generates more peritoneal damage than passive airflow and is reduced significantly by the use of humidified-warm CO2. Introduced peritoneal damage is largely repaired in mice by day 10 with gas. Desmoid tumor incidence is not increased substantially by surgery itself but rises over time following surgery compared to non-surgery mice

Primary squamous cell carcinoma of the rectum: An update and implications for treatment

AIM: To provide an update on the aetiology, pathogenesis, diagnosis, staging and management of rectal squamous cell carcinoma (SCC). METHODS: A systematic review was conducted according to the preferred reporting items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Ovid MEDLINE was performed with the reference list of selected articles reviewed to ensure all relevant publications were captured. The search strategy was limited to the English language, spanning from 1946 to 2015. A qualitative analysis was undertaken examining patient demographics, clinical presentation, diagnosis, staging, treatment and outcome. The quantitaive analysis was limited to data extracted on treatment and outcomes including radiological, clinical and pathological complete response where available. The narrative and quantitative review were synthesised in concert. RESULTS: The search identified 487 articles in total with 79 included in the qualitative review. The quantitative analysis involved 63 articles, consisting of 43 case reports and 20 case series with a total of 142 individual cases. The underlying pathogenesis of rectal SCC while unclear, continues to be defined, with increasing evidence of a metaplasia-dysplasia-carcinoma sequence and a possible role for human papilloma virus in this progression. The presentation is similar to rectal adenocarcinoma, with a diagnosis confirmed by endoscopic biopsy. Many presumed rectal SCC's are in fact an extension of an anal SCC, and cytokeratin markers are a useful adjunct in this distinction. Staging is most accurately reflected by the tumour-node-metastasis classification for rectal adenocarcinoma. It involves examining locoregional disease by way of magnetic resonance imaging and/or endorectal ultrasound, with systemic spread excluded by way of computed tomography. Positron emission tomography is integral in the workup to exclude an external site of primary SCC with metastasis to the rectum. While the optimal treatment remains as yet undefined, recent studies have demonstrated a global shift away from surgery towards definitive chemoradiotherapy as primary treatment. Pooled overall survival was calculated to be 86% in patients managed with chemoradiation compared with 48% for those treated traditionally with surgery. Furthermore, local recurrence and metastatic rates were 25% vs 10% and 30% vs 13% for the chemoradiation vs conventional treatment cohorts. CONCLUSION: The changing paradigm in the treatment of rectal SCC holds great promise for improved outcomes in this rare disease

Peritoneal Tumorigenesis and Inflammation are Ameliorated by Humidified-Warm Carbon Dioxide Insufflation in the Mouse

BACKGROUND: Conventional laparoscopic surgery uses CO2 that is dry and cold, which can damage peritoneal surfaces. It is speculated that disseminated cancer cells may adhere to such damaged peritoneum and metastasize. We hypothesized that insufflation using humidified-warm CO2, which has been shown to reduce mesothelial damage, will also ameliorate peritoneal inflammation and tumor cell implantation compared to conventional dry-cold CO2. METHODS: Laparoscopic insufflation was modeled in mice along with anesthesia and ventilation. Entry and exit ports were introduced to maintain insufflation using dry-cold or humidified-warm CO2 with a constant flow and pressure for 1 h; then 1000 or 1 million fluorescent-tagged murine colorectal cancer cells (CT26) were delivered into the peritoneal cavity. The peritoneum was collected at intervals up to 10 days after the procedure to measure inflammation, mesothelial damage, and tumor burden using fluorescent detection, immunohistochemistry, and scanning electron microscopy. RESULTS: Rapid temperature control was achieved only in the humidified-warm group. Port-site tumors were present in all mice. At 10 days, significantly fewer tumors on the peritoneum were counted in mice insufflated with humidified-warm compared to dry-cold CO2 (p < 0.03). The inflammatory marker COX-2 was significantly increased in the dry-cold compared to the humidified-warm cohort (p < 0.01), while VEGFA expression was suppressed only in the humidified-warm cohort. Significantly less mesothelial damage and tumor cell implantation was evident from 2 h after the procedure in the humidified-warm cohort. CONCLUSIONS: Mesothelial cell damage and inflammation are reduced by using humidified-warm CO2 for laparoscopic oncologic surgery and may translate to reduce patients' risk of developing peritoneal metastasis

Postmortem imaging of sudden cardiac death.

Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined channelopathies cannot be detected radiologically. This review underlines the need to establish the role of postmortem radiology in the diagnosis of SCD