Negative Pressure Wound Therapy. Therapy Settings and Biological Effects in Peripheral Wounds

Negative pressure wound therapy (NPWT) promotes wound healing through several mechanisms, e.g., altered periwound blood flow, mechanical deformation of the wound edge tissue, and drainage of excess fluid and debris. The general aim of this thesis was to study the impact of different levels of negative pressure, different wound filling materials (foam or gauze), and different ways of applying the negative pressure (continuously, intermittently or variably) on the biological effects of NPWT in peripheral wounds. The intention was to provide a scientific basis for the choice of these parameters in order to be able to optimize the healing of NPWT-treated wounds in the future. Studies were carried out on peripheral wounds created on the backs of pigs. The effect of NPWT on periwound blood flow was investigated using invasive and transcutaneous laser Doppler flowmetry, as well as thermodiffusion. Blood flow was found to decrease 0.5 cm laterally from the wound edge and increase 2.5 cm from the wound edge; a transition zone being seen 1 cm from the wound edge. Blood flow changed gradually with increasing levels of negative pressure, reaching half maximal effect at approximately –45 mmHg and maximum effect at about –80 mmHg. The blood flow response was found to depend on the measurement technique. Applying intermittent and variable pressure resulted in concomitant increases and decreases in periwound blood flow. The combination of hypo- and hyperperfusion may be beneficial in the process of wound healing. The mechanical effects of NPWT were studied with regards to macro- and microdeformation. It was found that the degree of macrodeformation, i.e., wound contraction, increased gradually with increasing negative pressure level, reaching half maximal effect at about –45 mmHg and near-maximal effect at –75 mmHg. The degree of wound contraction was the same regardless of whether foam or gauze was used as wound filler. The effects of NPWT on microdeformation, i.e., the microscopic interaction between the wound filler and the newly formed granulation tissue, were examined histologically using stained sections of the wound bed. Both foam- and gauze-based NPWT were shown to induce microdeformation of the wound bed tissue. The effect of NPWT on fluid evacuation from the wound cavity was measured gravimetrically. The amount of evacuated fluid increased gradually with increasing level of negative pressure, reaching a near-maximum at –125 mmHg. It may thus be beneficial to treat wounds containing large volumes of exudate with a high negative pressure initially (e.g., –125 mmHg), and then reduce the pressure to a level more appropriate for the wound edge tissue. In conclusion, the biological effects of NPWT were influenced by the negative pressure level, the wound filling material and the way in which NPWT was applied (continuously, intermittently or variably). Hopefully, the results of these studies may provide a scientific basis for the choice of NPWT parameters in the treatment of wounds. Further clinical studies are needed to corroborate our findings before recommendations can be made regarding the NPWT settings for treatment of different wound types and tissues in order to improve wound healing

Tumor-specific expression of HMG-CoA reductase in a population-based cohort of breast cancer patients

The mevalonate pathway synthetizes cholesterol, steroid hormones, and non-steriod isoprenoids necessary for cell survival. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) is the rate-limiting enzyme of the mevalonate pathway and the target for statin treatment. HMGCR expression in breast tumors has recently been proposed to hold prognostic and treatment-predictive information. This study aimed to investigate whether HMGCR expression in breast cancer patients was associated with patient and tumor characteristics and disease-free survival (DFS)

A case of septicaemic anthrax in an intravenous drug user

<p><b>Background:</b> In 2000, Ringertz et al described the first case of systemic anthrax caused by injecting heroin contaminated with anthrax. In 2008, there were 574 drug related deaths in Scotland, of which 336 were associated with heroin and or morphine. We report a rare case of septicaemic anthrax caused by injecting heroin contaminated with anthrax in Scotland.</p> <p><b>Case Presentation:</b> A 32 year old intravenous drug user (IVDU), presented with a 12 hour history of increasing purulent discharge from a chronic sinus in his left groin. He had a tachycardia, pyrexia, leukocytosis and an elevated C-reactive protein (CRP). He was treated with Vancomycin, Clindamycin, Ciprofloxacin, Gentamicin and Metronidazole. Blood cultures grew Bacillus anthracis within 24 hours of presentation. He had a computed tomography (CT) scan and magnetic resonance imagining (MRI) of his abdomen, pelvis and thighs performed. These showed inflammatory change relating to the iliopsoas and an area of necrosis in the adductor magnus.</p> <p>He underwent an exploration of his left thigh. This revealed chronically indurated subcutaneous tissues with no evidence of a collection or necrotic muscle. Treatment with Vancomycin, Ciprofloxacin and Clindamycin continued for 14 days. Negative Pressure Wound Therapy (NPWT) device was applied utilising the Venturi™ wound sealing kit. Following 4 weeks of treatment, the wound dimensions had reduced by 77%.</p> <p><b>Conclusions:</b> Although systemic anthrax infection is rare, it should be considered when faced with severe cutaneous infection in IVDU patients. This case shows that patients with significant bacteraemia may present with no signs of haemodynamic compromise. Prompt recognition and treatment with high dose IV antimicrobial therapy increases the likelihood of survival. The use of simple wound therapy adjuncts such as NPWT can give excellent wound healing results.</p&gt

Comparison of laser Doppler and laser speckle contrast imaging using a concurrent processing system

Full field laser Doppler imaging (LDI) and single exposure laser speckle contrast imaging (LSCI) are directly compared using a novel instrument which can concurrently image blood flow using both LDI and LSCI signal processing. Incorporating a commercial CMOS camera chip and a field programmable gate array (FPGA) the flow images of LDI and the contrast maps of LSCI are simultaneously processed by utilizing the same detected optical signals. The comparison was carried out by imaging a rotating diffuser. LDI has a linear response to the velocity. In contrast, LSCI is exposure time dependent and does not provide a linear response in the presence of static speckle. It is also demonstrated that the relationship between LDI and LSCI can be related through a power law which depends on the exposure time of LSCI

HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes

Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG-CoAR was positively associated with the expression of hormone receptors (ER, PgR, AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR-positive tumors compared with their negative counterparts (p = 0.031). Five- and 10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25–0.99, p = 0.048 and HR 0.53, 95% CI: 0.26–1.07, p = 0.078). Results were confirmed in a sensitivity analysis by excluding uncommon histotypes (multivariate Cox: HR 0.45, 95% CI: 0.21–0.97, p = 0.043). A positive relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting a connection between the mevalonate pathway, the hormonal milieu and Hippo in MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator

Методологія вітчизняної кримінально-правової науки: становлення історичного методу та проблеми наступності

Аналізуються методологічні проблеми кримінально-правової науки, зокрема процес становлення історичного методу та його ролі у вивченні питань наступності в кримінальному праві.Анализируются методологические проблемы уголовно-правовой науки, в частности процесс становления исторического метода и его роли в изучении вопросов преемственности в уголовном праве.The paper is devoted to an analysis of methodological problems of a criminal legal sci­ence, namely, an establishing process of historical method and its role in studying succession issues in a criminal law

Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation.

Limited epidemiological evidence suggests that the etiology of hormone receptor positive (HR+) breast cancer may differ by levels of histologic grade and proliferation. We pooled risk factor and pathology data on 5,905 HR+ breast cancer cases and 26,281 controls from 11 epidemiological studies. Proliferation was determined by centralized automated measures of KI67 in tissue microarrays. Odds ratios (OR), 95% confidence intervals (CI) and p-values for case-case and case-control comparisons for risk factors in relation to levels of grade and quartiles (Q1-Q4) of KI67 were estimated using polytomous logistic regression models. Case-case comparisons showed associations between nulliparity and high KI67 [OR (95% CI) for Q4 vs. Q1 = 1.54 (1.22, 1.95)]; obesity and high grade [grade 3 vs. 1 = 1.68 (1.31, 2.16)] and current use of combined hormone therapy (HT) and low grade [grade 3 vs. 1 = 0.27 (0.16, 0.44)] tumors. In case-control comparisons, nulliparity was associated with elevated risk of tumors with high but not low levels of proliferation [1.43 (1.14, 1.81) for KI67 Q4 vs. 0.83 (0.60, 1.14) for KI67 Q1]; obesity among women ≥50 years with high but not low grade tumors [1.55 (1.17, 2.06) for grade 3 vs. 0.88 (0.66, 1.16) for grade 1] and HT with low but not high grade tumors [3.07 (2.22, 4.23) for grade 1 vs. 0.85 (0.55, 1.30) for grade 3]. Menarcheal age and family history were similarly associated with HR+ tumors of different grade or KI67 levels. These findings provide insights into the etiologic heterogeneity of HR+ tumors

Prognostic impact of tumour-specific HMG-CoA reductase expression in primary breast cancer

Introduction We have previously reported that tumour-specific expression of the rate-limiting enzyme, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR), in the mevalonate pathway is associated with more favourable tumour parameters in breast cancer. In the present study, we examined the prognostic value of HMG-CoAR expression in a large cohort of primary breast cancer patients with long-term follow up. Methods The expression of HMG-CoAR was assessed by immunohistochemistry on tissue microarrays with tumour specimens from 498 consecutive cases of breast cancer with a median follow-up of 128 months. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the rate of recurrence-free survival (RFS) and breast cancer specific survival (BCSS). Results In line with our previous findings, tumour-specific HMG-CoAR expression was associated with low grade (p < 0.001), small size (p = 0.007), oestrogen receptor (ER) positive (p = 0.01), low Ki-67 (p = 0.02) tumours. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS, even when adjusted for established prognostic factors (relative risk [RR] = 0.60, 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In ER-negative tumours, however, there was a trend, that was not significantly significant, towards a shorter RFS in HMG-CoAR expressing tumours. Conclusions HMG-CoAR expression is an independent predictor of a prolonged RFS in primary breast cancer. This may, however, not be true for ER-negative tumours. Further studies are needed to shed light on the value of HMG-CoAR expression as a surrogate marker of response to statin treatment, especially with respect to hormone receptor status

Atrial high rate episodes predict clinical outcome in patients with cardiac resynchronization therapy

OBJECTIVES: Up to 50% of patients qualified for cardiac resynchronization therapy (CRT) have documented atrial fibrillation (AF) prior to CRT-implantation. This finding is associated with worse prognosis but few studies have evaluated the importance of post-implant device-detected AF. This study aimed to assess the prognostic impact of device-detected atrial high rate episodes (AHRE), as a surrogate for atrial fibrillation (AF).DESIGN: Data was retrospectively obtained from consecutive patients receiving CRT. Baseline clinical data and data from CRT device-interrogations, performed at a median of 12.2 months after CRT-implantation, were evaluated with regard to prediction of the composite endpoint of death, heart transplant or appropriate shock therapy. Median follow-up time was 51 months post-implant.RESULTS: The study included 377 patients. Preoperative AF was present in 49% and associated with worse outcome. The cumulative burden of AHRE at 12 months post-implant was an independent predictor of the primary endpoint. During the first 12 months after CRT-implantation, AHRE were detected in 25% of the patients with no preoperative diagnosis of AF. This finding was not associated with worse outcome.CONCLUSIONS: In CRT recipients, the cumulative burden of AHRE during first year of follow-up was associated with worse long-term clinical outcome. Prospective trials are needed to determine if a rhythm control strategy is to be preferred in patients with CRT

Given breast cancer, is fat better than thin? Impact of the estrogen receptor beta gene polymorphisms.

The role of estrogen receptor beta (ERβ) in breast cancer has been investigated since its identification in 1996. Studies based on protein expression have indicated that ERβ is a favorable prognostic marker. Further, ERβ expression is lower in obese breast cancer patients. Fewer studies have focused on the prognostic impact of ERβ polymorphisms. Therefore, we analyzed the associations between four previously identified haplotype tagging single nucleotide polymorphisms (htSNPs), associated haplo- and diplotypes, and breast cancer-free survival according to body constitution. The patient cohort included 634 women from the prospective breast cancer and blood study (BC Blood study, Sweden) with a median follow-up of 4.92 years. Four htSNPs (i.e., rs4986938, rs1256049, rs1256031, rs3020450) in the ESR2 gene and the correlating haplo- and diplotypes were analyzed and correlated to selected patient and tumor characteristics and to disease-free survival, including stratification for BMI. Based on the four htSNPs, seven haplotypes and eight diplotypes were identified. The patient and tumor characteristics were well-balanced across all geno- and haplotypes. Disease-free survival differed according to rs4986938 and rs1256031 (Log-Rank P = 0.045 and P = 0.041, respectively) and the number of haplotype copies of the wildtype CCGC and TCAC (Log-Rank P = 0.027 and P = 0.038, respectively). In the survival analyses stratified for BMI, significant survival differences between alleles were observed among overweight women (rs4986938 and rs1256031 with Log-Rank P = 0.001 and P = 0.001, respectively). The BMI-stratified survival analyses based on haplotypes showed shorter disease-free survival for overweight women with null copies of CCGC (Log-Rank P = 0.001) and for overweight women with any TCAC copy (Log-Rank P < 0.0001). Markedly impaired disease-free survival was found for genotypes in two out of four ESR2 htSNPs and for two haplotypes. ESR2 polymorphisms seem to divide patients into good and poor survivors based on BMI, stressing the need of taking host factors into consideration in the evaluation of prognostic markers