Efficacy of Mepliex® Ag Versus Xeroform® As A Split-Thickness Skin Graft Donor Site Dressing: Bad Habits Die Hard.

Autografting with split-thickness skin grafts (STSG) remains an essential procedure in burn and reconstructive surgery. The process of harvesting STSG, however, leaves behind a donor site, an exposed area of partial-thickness dermis left to heal by secondary intention. There has yet to be a consensus amongst surgeons regarding optimal management of the donor site. The ideal donor site dressing is one that allows for expeditious healing while minimizing pain and infection. Despite numerous studies demonstrating the superiority of moist wound healing, many surgeons continue to treat STSG donor sites dry, with petroleum-based gauze. In this study, two burn centers performed a retrospective review of burn patients whose STSG donor sites were treated with either Xeroform® or Mepilex® Ag dressings. Infections were documented and in a subgroup analysis of patients, postoperative pain scores were noted and total opiate usage during hospitalization was calculated. Analysis revealed an overall infection rate of 1.2% in the Mepilex® Ag group and 11.4% in the Xeroform® group (p<0.0001). Patients with Xeroform® donor site dressings had increased odds of donor site infection (OR=10.8, p=0.002). In subgroup analysis, there were no significant differences in maximum pain scores between Mepilex® Ag and Xeroform® groups, nor were there differences in opiate usage. STSG donor sites dressed with silver foam dressings have a lower rate of donor site infection relative to those dressed with petroleum-based gauze. Moist donor site dressings such as foam dressings (including Mepilex® Ag) should be the standard of care in STSG donor site wound care.

La greffes de peau mince (GPM) demeure une procédure essentielle dans la chirurgie de brûlure et de reconstruction. La zone donneuse de greffe (ZDG) représente une perte de substance cutanée superficielle, cicatrisant spontanément. Il n'y a pas de consensus concernant la prise en charge optimale de la ZDG. Le pansement idéal de la ZDG doit promouvoir la cicatrisation et réduire la douleur ainsi que le risque infectieux. Malgré les nombreuses publications montrant l'intérêt d'un environnement humide pour la cicatrisation, de nombreux chirurgiens réalisent des pansements secs vaselinés. Cette étude rétrospective effectuée dans 2 CTB compare les pansements de ZDG réalisés au Xéroform® ou au Mepilex Ag®. Les infections ont été documentées et, dans un sous-groupe, les scores de douleur et la consommation d'opiacés au long de l'hospitalisation ont été notés. Les taux d'infection sont de 1,2% dans le groupe Mepilex Ag® et 11,4% avec Xéroform® (p<0,0001). Le risque d'infection de la ZDG est augmenté (OR 10,8 ; p = 0,002) en cas d'utilisation de Xéroform®. Il n'y avait pas de différence de douleur et de consommation d'opiacés entre les 2 groupes. Les ZDG recouvertes d'un pansement hydrocellulaire imprégné d'argent s'infectent moins que celles traitées avec une gaze imprégnée de vaseline. L'utilisation sur les ZDG d'un pansement humide comme une mousse hydrocellulaire (par exemple Mepilex Ag®) devrait devenir la norme.

A systematic review of the impact of contemporary treatment modalities for cervical cancer on women's self-reported health-related quality of life.

PURPOSE: Given the high survival rate of cervical cancer patients, understanding women's health-related quality of life (HRQL) during and after treatment is of major clinical importance. We conducted a systematic review to synthesize all available evidence about the effects of each contemporary treatment modality for cervical cancer on all dimensions of women's HRQL, including symptoms, functioning, and global HRQL. METHODS: We searched four electronic databases from January 2000 to September 2019, cross-referenced and searched by author name for studies of patients treated for cervical cancer that reported patient-reported outcomes (PROs) before treatment and with at least one post-treatment measurement. Two independent reviewers applied inclusion and quality criteria and extracted findings. Studies were categorized by treatment to determine specific treatment effects on PROs. Results were narratively summarized. RESULTS: We found twenty-nine papers reporting 23 studies. After treatments with curative intent for early or locally advanced disease, lymphedema, diarrhea, menopausal symptoms, tight and shorter vagina, pain during intercourse, and sexual worries remained long-term problems; however, sexual activity improved over time. HRQL and psychological distress were impacted during treatment with also worsening of global HRQL but improved 3-6 months after treatment. In patients with metastatic or recurrent disease, pain improved during palliative treatment or remained stable, with no differences in global HRQL found over time. CONCLUSION: Whereas most symptoms worsen during treatment and improve in the first 3 months after completing treatment, symptoms like lymphedema, menopausal symptoms, and sexual worries develop gradually and persist after curative treatment. These findings can be used to inform clinical practice and facilitate communication and shared decision-making. More research is needed in very early cervical cancer and the impact of fertility sparing therapy on PROs.

The prevalence of medical reasons for non-participation in the Scottish breast and bowel cancer screening programmes.

OBJECTIVE: Increasing uptake of cancer screening is a priority for health systems internationally, however, some patients may not attend because they are undergoing active treatment for the cancer of interest or have other medical reasons that mean participation would be inappropriate. This study aims to quantify the proportion of non-participants who have a medical reason for not attending cancer screening. METHODS: Medical reasons for not participating in breast and bowel screening were defined a priori on the basis of a literature review and expert opinion. The notes of 700 patients at two GP practices in Scotland were reviewed, to ascertain the prevalence of medical reasons amongst non-participants. Simple proportions and confidence intervals were calculated. RESULTS: 17.4% of breast and 2.3% of bowel screening non-participants had a medical reason to not participate. The two most common reasons were previous breast cancer follow up (8.86%) and recent mammogram (6.57%). CONCLUSION: These patients may not benefit from screening while also being distressed by receiving an invitation. This issue also makes accurate monitoring and target-setting for improving uptake difficult. Further work is needed to estimate robustly the extent to which medical reasons account for screening non-participation in a larger population.

Downregulation of Mcl-1 has anti-inflammatory pro-resolution effects and enhances bacterial clearance from the lung.

Phagocytes not only coordinate acute inflammation and host defense at mucosal sites, but also contribute to tissue damage. Respiratory infection causes a globally significant disease burden and frequently progresses to acute respiratory distress syndrome, a devastating inflammatory condition characterized by neutrophil recruitment and accumulation of protein-rich edema fluid causing impaired lung function. We hypothesized that targeting the intracellular protein myeloid cell leukemia 1 (Mcl-1) by a cyclin-dependent kinase inhibitor (AT7519) or a flavone (wogonin) would accelerate neutrophil apoptosis and resolution of established inflammation, but without detriment to bacterial clearance. Mcl-1 loss induced human neutrophil apoptosis, but did not induce macrophage apoptosis nor impair phagocytosis of apoptotic neutrophils. Neutrophil-dominant inflammation was modelled in mice by either endotoxin or bacteria (Escherichia coli). Downregulating inflammatory cell Mcl-1 had anti-inflammatory, pro-resolution effects, shortening the resolution interval (Ri) from 19 to 7 h and improved organ dysfunction with enhanced alveolar-capillary barrier integrity. Conversely, attenuating drug-induced Mcl-1 downregulation inhibited neutrophil apoptosis and delayed resolution of endotoxin-mediated lung inflammation. Importantly, manipulating lung inflammatory cell Mcl-1 also accelerated resolution of bacterial infection (Ri; 50 to 16 h) concurrent with enhanced bacterial clearance. Therefore, manipulating inflammatory cell Mcl-1 accelerates inflammation resolution without detriment to host defense against bacteria, and represents a target for treating infection-associated inflammation.

Improved outcome after lumbar microdiscectomy in patients shown their excised disc fragments: a prospective, double blind, randomised, controlled trial.

BACKGROUND: Lumbar microdiscectomy (LMD) is a commonly performed neurosurgical procedure. We set up a prospective, double blind, randomised, controlled trial to test the hypothesis that presenting the removed disc material to patients after LMD improves patient outcome. METHODS: Adult patients undergoing LMD for radiculopathy caused by a prolapsed intervertebral disc were randomised into one of two groups, termed experimental and control. Patients in the experimental group were given their removed disc fragments whereas patients in the control group were not. Patients were unaware of the trial hypothesis and investigators were blinded to patient group allocation. Outcome was assessed between 3 and 6 months after LMD. Primary outcome measures were the degree of improvement in sciatica and back pain reported by the patients. Secondary outcome measures were the degree of improvement in leg weakness, paraesthesia, numbness, walking distance and use of analgesia reported by the patients. RESULTS: Data from 38 patients in the experimental group and 36 patients in the control group were analysed. The two groups were matched for age, sex and preoperative symptoms. More patients in the experimental compared with the control group reported improvements in leg pain (91.5 vs 80.4%; p<0.05), back pain (86.1 vs 75.0%; p<0.05), limb weakness (90.5 vs 56.3%; p<0.02), paraesthesia (88 vs 61.9%; p<0.05) and reduced analgesic use (92.1 vs 69.4%; p<0.02) than preoperatively. CONCLUSION: Presentation of excised disc fragments is a cheap and effective way to improve outcome after LMD.

Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases.

Glioblastoma is the most common primary brain tumour. The aim of this study was to determine trends in survival over a 12-year period. Survival data were collected retrospectively for 625 patients who had surgery for histologically-confirmed glioblastoma between 1993 and 2004 in a single centre. Data including age, sex, preoperative Karnofsky performance score, tumour site, date of surgery, and type of surgical and adjuvant treatment were collected. Overall median survival was 189 days; there was no significant change in survival over 12 years. Multivariate analysis identified the following independent positive prognostic factors: age <60 years (p < 0.0005), Karnofsky score > or = 70 (p < 0.0001), tumour debulking, rather than biopsy (p < 0.001), right-sided lesion (p < 0.05), unilateral tumour (p < 0.05) and radiotherapy (p < 0.0001). Despite neurosurgical advances, the survival of patients with glioblastoma has not changed for more than a decade. Although, overall, glioblastoma has a short survival, our data show that individual patient survival is heterogeneous.

How much can be concluded from the International Subarachnoid Aneurysm Trial (ISAT)?

Recently published data from the International Subarachnoid Aneurysm Trial (ISAT) shows that for patients enrolled in the trial there is a 7.4% reduction in the incidence of death or dependency at 1 year if they undergo coiling, rather than clipping. Furthermore, extrapolation of longer-term follow-up data for patient mortality appears to suggest that this advantage will be maintained in the longer term. Based on a reassessment of the published data, the authors note: (1) the incidence of rebleeding following treatment is approximately three times higher in the coiled group (p<0.001); (2) the need for aneurysm retreatment is likely to be higher in the coiled group; (3) trends in longer-term mortality data are not a reliable basis for predicting future outcomes of the trial; (4) trends in longer-term morbidity data are more reliable and suggest that the advantage of coiling diminishes with time; (5) The absence of up-to-date published rates of aneurysm retreatment and of longer-term rates of death or dependence makes ISAT extremely hard to interpret. It is far from clear that the early advantage of coiling will be maintained in the future and, hence, longer follow-up is required. Treatment of aneurysms is a continually evolving field and there is currently no other major source of information concerning management of aneurysms. For these reasons the authors recommend the instigation of a national aneurysm registry to prospectively collect data.

Intracellular cyclic nucleotide analogues inhibit in vitro mitogenesis and activation of fibroblasts derived from obstructed rat kidneys.

As several studies indirectly suggest that inhibiting the intracellular breakdown of cyclic nucleotides may inhibit fibrogenesis, this study used membrane permeable cyclic nucleotide analogues to examine the role of cAMP and cGMP signaling pathways in the regulation of renal fibroblast function. Fibroblasts were isolated by explant outgrowth culture of rat kidneys post unilateral ureteric obstruction. Subcultured cells were exposed to 10- 1,000 microM of the cyclic nucleotide analogues 8-bromo-cAMP (8br-cAMP) and 8-bromo-cGMP (8br-cGMP). Functional parameters examined included mitogenesis (thymidine incorporation), collagen synthesis (proline incorporation), myofibroblast differentiation (Western blotting for alpha-smooth muscle actin; alpha-SMA) and expression of CTGF (Northern blotting), a TGF-beta(1)-driven immediate early response gene. Serum-stimulated mitogenesis was decreased 27 +/- 4% by 100 microM 8br-cAMP (p < 0.01), 49 +/- 6% by 1,000 microM 8br-cAMP (p < 0.001) and 43 +/- 7% by 1,000 microM 8br-cGMP (p < 0.01). 1,000 microM 8br-cAMP and 8br-cGMP reduced basal collagen synthesis by 80 +/- 5 and 60 +/- 21% respectively (both p < 0.05). Maximum dose of 8br-cAMP but not 8br-cGMP inhibited basal expression of the differentiation marker alpha-SMA by 43 +/- 33 (p < 0.05), resulted in a more rounded cell morphology and reduced expression of CTGF by 39 +/- 24% (p < 0.05). Measurement of mitochondrial activity confirmed that effects were independent of cell toxicity. In conclusion, cyclic nucleotides inhibit fibrogenesis in vitro. Strategies which elevate intracellular cyclic nucleotide concentrations may therefore be therapeutically valuable in preventing the proliferation and activation of fibroblasts in progressive renal disease.

Smokeless nicotine administration is associated with hypertension but not with a deterioration in glucose tolerance in rats.

Cigarette smoking is a major risk factor for coronary heart disease. To further investigate the relationship of nicotine with other cardiac risk factors, we studied the impact of nicotine on blood pressure and glucose tolerance. Adult male Sprague-Dawley rats were randomly assigned to receive nicotine or placebo pellets implanted subcutaneously. Weight gain was controlled by pair-feeding, and was not significantly different between nicotine- and placebo-treated animals. Blood pressure (in mm Hg) increased throughout a 3-week treatment period in nicotine-treated animals and was significantly higher [P < .05 by two-way ANOVA] than in placebo-treated rats. Blood pressure returned to normal within 1 week following exhaustion of the pellets. Oral glucose tolerance tests performed 2.5 weeks after pellet placement showed similar glucose, insulin, and free fatty acid (FFA) profiles by two-way ANOVA. In summary, smokeless nicotine exposure leads to sustained but reversible hypertension without deterioration in glucose tolerance or insulin action when weight gain is controlled. We conclude that in rats smokeless nicotine adversely affects the coronary risk profile by increasing blood pressure.

Comparative study of the inhibition of rat and tobacco squalene synthase by squalestatins.

Squalestatins 1-3 and a series of S1 analogues modified at the C-1, C-3, C-4 or C-6 position were able to inhibit squalene synthase, a key enzyme in both cholesterol and phytosterol biosynthesis, in microsomal rich preparations from both rat liver and N. tabacum. IC50 values varied between 4 and 2000 nM, and similar inhibition values were observed in both systems. The structural requirements for maximal activity at each position are discussed.

Susceptibility of Pseudomonas and Staphylococcus wound isolates to topical antimicrobial agents: a 10-year review and clinical evaluation.

A 10-year review of Ps. aeruginosa and Staph. aureus susceptibility to various topical agents is presented. Susceptibility testing was performed using the agar well diffusion (AWD) method. A reduction in microbial growth to numbers less than 10(5) per gram of tissue in the wound, measured by quantitative biopsy, was compared with predicted susceptibility test results. In this measurement of clinical efficacy, silver sulphadiazine and mafenide acetate compared most favourably with AWD results, 83 per cent and 82 per cent respectively. However, nitrofurazone only reduced bacterial counts to less than 10(5) per gram 42 per cent of the time when an inhibition zone was present. Hydrogen peroxide solution (1 per cent) was 100 per cent effective by the AWD test, but no relationship to clinical efficacy could be shown. Minimal inhibitory concentration (MIC) data for gentamicin sulphate was compared to AWD and showed a positive relationship of greater than 80 per cent for both organisms. The AWD test has been a useful aid in the decision-making process for the choice of topical agent by providing data which eliminates agents inappropriate for use.

Rapid quantification of bacterial and fungal growth in burn wounds: biopsy homogenate Gram stain versus microbial culture results.

A prospective analysis of 370 burn wound biopsies was done to correlate Gram-stain results from biopsy homogenates with quantitative culture results. The number of bacteria seen in a total of 10 oil immersion microscope fields of Gram-stained homogenates was correlated with significant microbial growth (1 x 10(5) organisms/gram of tissue) of the same biopsy homogenate plated on trypticase soy agar. Of the biopsies examined, Gram-negative rods were present in 36.8 per cent, Gram-positive cocci in 49.7 per cent and yeast in 15.9 per cent. Mixtures of organisms were present in 24.3 per cent. When Gram stains showed one or more organisms per oil immersion microscope field, the correlation with significant microbial growth was 94.5 per cent or more. When five or more organisms were seen per field, the correlation with significant growth became 97 per cent or greater. When no organism was seen on Gram stain, the cultures grew significant numbers of organisms 19.1 per cent of the time or less. This false-negative rate was considered to be high. It is believed, however, that this method of early detection of significant burn wound microbial growth may prove to be valuable in the management of severely burned patients.

Spiral filling defect in the common bile duct.

A spiral filling defect in the common bile duct was found in an elderly woman with intermittent obstructive jaundice. A large, smooth papilla was shown on hypotonic duodenogram. At laparotomy, mucus strans were found in the DUCT, and ampullary carcinoma in the duodenum. The significance of the mucus strand and large duodenal papilla is discussed.