KLF4 Promotes Diabetic Chronic Wound Healing by Suppressing Th17 Cell Differentiation in an MDSC-Dependent Manner.

OBJECTIVES: Diabetic wound inflammation deficiencies lead to ulcer development and eventual amputation and disability. Our previous research demonstrates that myeloid-derived suppressor cells (MDSCs) accumulate during inflammation and promote chronic wound healing via the regulation of Kruppel-like factor 4 (KLF4). In this study, we aimed to investigate the potential roles of MDSCs and KLF4 in diabetic wound healing. METHODS: An ob/ob mouse pressure ulcer (PU) model was used to evaluate the process of wound healing. The expression levels of KLF4 and IL-17A were measured by real-time PCR, and the population of MDSCs and Th17 cells was measured by flow cytometry. The levels of cytokines were determined by an immunosuppression assay. RESULTS: KLF4 deficiency in the diabetic PU model resulted in decreased accumulation of MDSCs, increased expansion of Th17 cells, and significantly delayed wound healing. Conversely, KLF4 activation by APTO-253 accelerated wound healing accompanied by increased MDSC populations and decreased numbers of Th17 cells. MDSCs have been proven to mediate Th17 differentiation via cytokines, and our in vitro data showed that elevated KLF4 expression in MDSCs resulted in reduced Th17 cell numbers and, thus, decreased levels of cytokines indispensable for Th17 differentiation. CONCLUSIONS: Our study revealed a previously unreported function of KLF4-regulated MDSCs in diabetic wound healing and identified APTO-253 as a potential agent to improve the healing of pressure ulcers.

miR-19a/b and miR-20a Promote Wound Healing by Regulating the Inflammatory Response of Keratinocytes.

Persistent and impaired inflammation impedes tissue healing and is a characteristic of chronic wounds. A better understanding of the mechanisms controlling wound inflammation is needed. In this study, we show that in human wound-edge keratinocytes, the expressions of microRNA (miR)-17, miR-18a, miR-19a, miR-19b, and miR-20a, which all belong to the miR-17∼92 cluster, are upregulated during wound repair. However, their levels are lower in chronic ulcers than in acute wounds at the proliferative phase. Conditional knockout of miR-17∼92 in keratinocytes as well as injection of miR-19a/b and miR-20a antisense inhibitors into wound edges enhanced inflammation and delayed wound closure in mice. In contrast, conditional overexpression of the miR-17∼92 cluster or miR-19b alone in mice keratinocytes accelerated wound closure in vivo. Mechanistically, miR-19a/b and miR-20a decreased TLR3-mediated NF-κB activation by targeting SHCBP1 and SEMA7A, respectively, reducing the production of inflammatory chemokines and cytokines by keratinocytes. Thus, miR-19a/b and miR-20a being crucial regulators of wound inflammation, the lack thereof may contribute to sustained inflammation and impaired healing in chronic wounds. In line with this, we show that a combinatory treatment with miR-19b and miR-20a improved wound healing in a mouse model of type 2 diabetes.

Assessing subclinical inflammation by peroxidase detection in patients with pressure ulcers.

OBJECTIVE: This study aimed to examine the superiority of peroxidase detection of macroscopic observations using rat wounds, and to test the external validity of the peroxidase analysis in pressure ulcers (PU) in humans. METHOD: In the animal study, rat wounds were analysed. A cross-sectional study analysed, by wound blotting, exudate samples from full-thickness PUs. Peroxidase activity was divided into two groups (ring and non-ring signals). Scores in the 'inflammation/infection' and 'necrotic tissue' components of DESIGN, a classification tool of PUs, were compared between the groups. RESULTS: In the animal study, 20 rat wounds were assessed and in the clinical study, 62 samples were collected from 26 full-thickness PUs of 21 patients aged ≥ 65 years. In the animal study, five of six wounds with clinical inflammation signs showed ring signal (defined as a signal on the wound edge and no signal on the wound bed). While the tissue sections of three wounds with a ring signal showed inflammatory features, they showed no clinical signs of 'inflammation/infection'. In the clinical study, which analysed 630 ring and 32 non-ring signals, 13 samples in the ring signal group and five in the non-ring signal group had 'inflammation/infection; scores of ≥1 (p=0.016). Despite having no clinical signs, 17 samples showed the ring signal. CONCLUSION: This study revealed the external validity of the wound blotting analysis of peroxidase and demonstrated its use to detect subclinical inflammation.

Topical application of quercetin improves wound healing in pressure ulcer lesions.

The ischaemia-reperfusion (I/R)-induced skin lesion has been identified as primary cause of pressure ulcers. To date, attempts to prevent pressure ulcers have not produced a significant improvement. Quercetin, one of the most widely distributed flavonoids in fruits and vegetables, exhibits its antioxidant and anti-inflammatory properties against many diseases, including ischaemic heart disease, atherosclerosis and renal injury. In vitro wound scratch assay was first used to assess the function of quercetin in wounding cell model. Next, animal pressure ulcers model was established with two cycles of I/R. The impact of quercetin in the wound recovery, immune cell infiltration and pro-inflammatory cytokines production was investigated in this model. Mechanistic regulation of quercetin at the wound site was also studied. Quercetin accelerated wound closure in cell scratch assay. Dose-response study suggested 1 µmol/L quercetin for in vivo study. In I/R injury model, quercetin treatment significantly accelerated wound closure, reduced immune cell infiltration and pro-inflammatory cytokines production. Signalling study showed quercetin treatment inhibited MAPK but not NFĸB activation. Quercetin treatment improved the wound healing process in I/R lesions by suppressing MAPK pathway. Our results supported that quercetin could be a potential therapeutic agent for pressure ulcers.

The impact of ischemia-reperfusion injuries on skin resident murine dendritic cells.

Pressure ulcers are a chronic problem for patients or the elderly who require extended periods of bed rest. The formation of ulcers is due to repeated cycles of ischemia-reperfusion (IR), which initiates an inflammatory response. Advanced ulcers disrupt the skin barrier, resulting in further complications. To date, the immunological aspect of skin IR has been understudied, partly due to the complexity of the skin immune cells. Through a combination of mass cytometry, confocal imaging and intravital multiphoton imaging, this study establishes a workflow for multidimensionality single cell analysis of skin myeloid cell responses in the context of IR injury with high spatiotemporal resolution. The data generated has provided us with previously uncharacterized insights into the distinct cellular behavior of resident dendritic cells (DCs) and recruited neutrophils post IR. Of interest, we observed a drop in DDC numbers in the IR region, which was subsequently replenished 48h post IR. More importantly, in these cells, we observe an attenuated response to repeated injuries, which may have implications in the subsequent wound healing process.

Effect of a wound cleansing solution on wound bed preparation and inflammation in chronic wounds: a single-blind RCT.

OBJECTIVE: Research into surfactant solutions for the debridement of chronic wounds suggests that surfactants may support wound bed preparation (WBP) in chronic wounds, however their efficacy has not been evaluated in randomised controlled trials (RCTs). Our aim was to assess the clinical efficacy of a propylbetaine-polihexanide (PP) solution versus normal saline (NS) solution in WBP, assessing inflammatory signs and wound size reduction in patients with pressure ulcers (PUs) or vascular leg ulcers. METHOD: In a single-blinded randomised controlled trial (RCT) patients were randomly allocated to two groups and treated with either propylbetaine-polihexanide (PP) solution (Prontosan) or NS. Wounds were assessed using the Bates-Jensen wound assessment tool (BWAT). Assessments took place at inclusion (T0), day 7 (T1), day 14 (T2), day 21 (T3), and day 28 (T4). Outcomes were analysed using a two-tailed Student's t-test. RESULTS: A total of 289 patients were included. Both groups had similar demographics, clinical status, and wound characteristics. Data analysis showed statistically significant differences between T0 and T4 for the following outcomes: BWAT total score, p=0.0248; BWAT score for inflammatory items, p=0.03; BWAT scores for wound size reduction (p=0.049) and granulation tissue improvement (p=0.043), all in favour of PP. The assessment of pain did not show any significant difference between the two groups. CONCLUSION: The study results showed significantly higher efficacy of the PP solution versus NS solution, in reducing inflammatory signs and accelerating the healing of vascular leg ulcers and PUs. This evidence supports the update of protocols for the care of chronic wounds. DECLARATION OF INTEREST: The authors have no conflict of interest regarding this research. This is an investigator initiated trial. B. Braun Milano SpA kindly provided the material under investigation for both treatment groups, and paid the Ethics Committees' application fees in all participating centres.

Utility of frozen section analysis for fungal organisms in soft tissue wound debridement margin determination.

BACKGROUND: Zygomycetes cause different patterns of infection in immunosuppressed individuals, including sino-orbito-cerebral, pulmonary, skin/soft tissue infection and disseminated disease. Infections with Zygomycetes have a high mortality rate, even with prompt treatment, which includes anti-fungal agents and surgical debridement. In some centers, clear margins are monitored by serial frozen sections, but there are no specific guidelines for the use of frozen sections during surgical debridement. Studies in fungal rhinosinusitis found 62.5-85 % sensitivity of frozen section analysis in margin assessment. However, the utility of frozen section analysis for margin evaluation in debridement of skin/soft tissue infection has not been published. METHODS: We present a case of zygomycosis of decubitus ulcers in which we assessed statistical measures of performance of frozen section analysis for presence of fungal organisms on the margin, compared with formalin-fixed paraffin embedded (FFPE) sections as gold standard. A total of 33 specimens (94 blocks) were sectioned, stained with H&E and evaluated by both frozen and FFPE analysis. Negative interpretations were confirmed by Gomori methenamine silver stain on FFPE sections. RESULTS: H&E staining of frozen sections had 68.4 % sensitivity and 100 % specificity for assessing margins clear of fungal organisms. The negative and positive predictive values were 70.0 % and 100 %, respectively. Using presence of acute inflammation and necrosis as markers of fungal infection improved sensitivity (100 %) at the expense of specificity (42.9 %). CONCLUSION: Use of intraoperative assessment of skin and soft tissue margins for fungal infection is a valuable tool in the management of skin and soft tissue fungal infection treatment.

Local blockage of EMMPRIN impedes pressure ulcers healing in a rat model.

Excessive extracellular matrix degradation caused by the hyperfunction of matrix metalloproteinases (MMPs) has been implicated in the failure of pressure ulcers healing. EMMPRIN, as a widely expressed protein, has emerged as an important regulator of MMP activity. We hypothesize that EMMPRIN affects the process of pressure ulcer healing by modulating MMP activity. In the rat pressure ulcer model, the expression of EMMPRIN in ulcers detected by Western blot was elevated compared with that observed in normal tissue. To investigate the role of EMMPRIN in regulating ulcer healing, specific antibodies against EMMPRIN were used via direct administration on the pressure ulcer. Local blockage of EMMPRIN resulted in a poor ulcer healing process compared with control ulcers, which was the opposite of our expectation. Furthermore, inhibiting EMMPRIN minimally impacted MMP activity. However, the collagen content in the pressure ulcer was reduced in the EMMPRIN treated group. Angiogenesis and the expression of angiogenic factors in pressure ulcers were also reduced by EMMPRIN local blockage. The results in the present study indicate a novel effect of EMMPRIN in the regulation of pressure ulcer healing by controlling the collagen contents and angiogenesis rather than MMPs activity.

Analysis of Gene Expression in Experimental Pressure Ulcers in the Rat with Special Reference to Inflammatory Cytokines.

Pressure ulcers have been investigated in a few animal models, but the molecular mechanisms of pressure ulcers are not well understood. We hypothesized that pressure results in up-regulation of inflammatory cytokines and those cytokines contribute to the formation of pressure ulcers. We measured genome-wide changes in transcript levels after compression, and focused especially on inflammatory cytokines. The abdominal wall of rats was compressed at 100 mmHg for 4 hours by two magnets. Specimens were obtained 12 hours, 1, or 3 days after compression, and analyzed by light microscopy, microarray, Real-Time PCR, and ELISA. The skin and subcutaneous tissue in the compressed area were markedly thickened. The microarray showed that numerous genes were up-regulated after the compression. Up-regulated genes were involved in apoptosis, inflammation, oxidative stress, proteolysis, hypoxia, and so on. Real-Time PCR showed the up-regulation of granulocyte-macrophage colony stimulating factor (GM-CSF), interferon γ (IFN-γ), interleukin 1ß (IL-1ß), interleukin 1 receptor antagonist gene (IL1Ra), interleukin 6 (IL-6), interleukin 10 (IL-10), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 1 (TIMP-1), and tumor necrosis factor α (TNF-α) at 12 hours, IFN-γ, IL-6, IL-10, MMP-3, and TIMP-1 at 1 day, and IFN-γ, IL-6, and MMP-3 at 3 days. Some genes from subcutaneous tissue were up-regulated temporarily, and others were kept at high levels of expression. ELISA data showed that the concentrations of IL-1ß and IL-6 proteins were most notably increased following compression. Prolonged up-regulation of IL-1ß, and IL-6 might enhance local inflammation, and continuous local inflammation may contribute to the pressure ulcer formation. In addition, GM-CSF, IFN-γ, MMP-3, and TIMP-1 were not reported previously in the wound healing process, and those genes may have a role in development of the pressure ulcers. Expression data from Real-Time PCR were generally in good agreement with those of the microarray. Our microarray data were useful for identifying genes involved in pressure ulcer formation. However, the expression levels of the genes didn't necessarily correspond with protein production. As such, the functions of these cytokines need to be further investigated.

Expression of cytokines, growth factors and apoptosis-related signal molecules in chronic pressure ulcer wounds healing.

OBJECTIVES: Many complex mechanisms responsible for the pathogenesis of pressure ulcers (PUs) currently remain poorly understood. The objective of this study was to discover the major roles for inflammatory cytokines, growth factors and several apoptosis-related signal molecules in chronic PU wound. METHODS: We investigated expression of inflammatory cytokines, growth factors and their corresponding receptors, and the apoptosis signal of caspase-3 in chronic stage III/IV chronic PU wound, acute wounds as well as normal skin controls. Tissues were stained by hematoxylin and eosin (HE) for histopathology and Masson's trichrome for collagen. Vascular endothelial growth factor (VEGF), fibroblast growth factors 2 (bFGF) and caspase-3 were detected by immunohistochemical analysis. Expression of mRNAs for interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), VEGF, KDR, bFGF and FGFR1 was determined by real-time reverse transcription PCR. RESULTS: Stage III and IV chronic PUs stained had increased inflammatory cell infiltration and decreased collagen compared with controls. Levels of mRNAs for inflammatory cytokines IL-1ß and TNF-α were elevated in PUs compared with acute wounds and normal skin. VEGF and bFGF, together with their receptors KDR and FGFR1, respectively, were significantly decreased compared with controls. However, the expression levels of caspase-3 were elevated in the PUs. CONCLUSION: Our series of studies have shown that chronic PUs displayed high levels of inflammation and disruption of the collagen matrix, along with increased indications of apoptosis and decreased levels of growth factors and their receptors. These characteristics can be used to comprehensively evaluate the etiology and treatment of chronic PUs.

Management of "difficult" wounds.

Pressure sores (PSs) and wounds in immunocompromised children are rather rare conditions. No doubt, their management is often complex and difficult, even for experienced pediatric plastic surgeons. As there are no algorithms for standard care, the therapeutic approach is individual.Successful PS management always implies primary and secondary prevention. With a PS present, rapid relief of pressure is crucial. If local wound care fails to restore skin integrity within a short period of time, surgical defect closure is mandatory. Overall, full-thickness skin grafts and local flap surgery are the most suitable methods regarding result quality, procedure complexity, and risks. Negative pressure wound therapy (NPWT) plays an instrumental role in wound bed preparation before definitive coverage. Recurrence rate is high (the complication). It does not much depend on the surgical technique employed, but rather depends on whether the various pathogenic factors leading to PS can be eliminated or alleviated.In both temporarily and permanently immunocompromised children, wound healing is significantly impaired. At the same time, these patients have no or low host defense activity. Thus, they are at high risk not only for local wound infection but also for potentially life threatening septic complications. Rapid and definitive wound closure is therefore essential. When conservative therapy fails, simple surgical techniques granting rapid and definitive wound closure should be used.

Wound blotting: a convenient biochemical assessment tool for protein components in exudate of chronic wounds.

Because wound exudate includes secreted proteins that affect wound healing, its biochemical analysis is useful for objective assessment of chronic wounds. Wound blotting allows for collection of fresh exudate by attaching a nitrocellulose membrane onto the wound surface. To determine its applicability for several analysis methods and its executability in clinical wound assessment, this study comprised an animal experiment and clinical case reports. In the animal experiment, full-thickness wounds were created on the dorsal skin of mice, and exudate samples were collected daily by a conventional method and by wound blotting. Extremely small but adequate volumes of exudate were collected by wound blotting for subsequent analysis in the animal experiments. Immunostaining showed the concentration and distribution of tumor necrosis factor (TNF) α. The activity of alkaline phosphatase was visualized by reaction with chemiluminescent substrate. The TNF distribution analysis indicated three different patterns: wound edge distribution, wound bed distribution, and a mostly negative pattern in both the animal and clinical studies, suggesting association between the TNF distribution pattern and wound healing. Our results indicate that wound blotting is a convenient method for biochemical analysis of exudate and a candidate tool with which to predict the healing/deterioration of chronic ulcers.

Chronic wound-associated pain, psychological stress, and wound healing.

Pain is an unpleasant sensory experience that evokes negative emotions and erodes an individual's quality of life, constituting a significant amount of stress. Chronic-wound patients have described pain as most intense during dressing change and the worst part of living with an ulcer. Wound-related pain is complex, involving a multitude of physiologic and psychologic factors, such as emotional state, culture, personality, meaning, and expectation. Although the exact mechanism(s) remains elusive, a burgeoning body of evidence suggests a close link between stress/anxiety and pain. Wound healing can be compromised by overproduction of cortisol compromising the function of immune system in addition to catecholamines causing vasoconstriction and poor tissue oxygenation. The purpose of this paper is to review the relationships among pain, stress, and wound healing.

Impact of a nutritional formula enriched in fish oil and micronutrients on pressure ulcers in critical care patients.

BACKGROUND: Pressure ulcers are an important source of morbidity and suffering for patients and a formidable burden on caregivers. OBJECTIVES: To assess the impact of a feeding formula enriched with fish oil on healing of preexisting pressure ulcers and serum levels of C-reactive protein in critical care patients. METHODS: Adult patients with pressure ulcers grade II or higher were randomly allocated to receive either a formula enriched with fish oil or an isocaloric control formula. Wound healing was assessed by using the Pressure Ulcer Scale for Healing tool on days 7, 14, and 28. Blood levels of C-reactive protein were measured on days 0, 7, and 14. RESULTS: Baseline demographics did not differ between the study (n = 20) and the control (n = 20) groups. The mean score on the ulcer healing tool increased significantly (P = .02) from day 0 to day 28 in the control group (from 9.25 [SD, 2.12] to 10.75 [SD, 3.41]) compared with the study group (from 9.10 [SD, 2.84] to 9.40 [SD, 3.72]). Mean levels of C-reactive protein decreased significantly (P= .02) from day 0 to day 14 in the study group (from 191 [SD, 104.4] mg/L to 111.7 [SD, 97.8] mg/L) compared with the control group (from 145 [SD, 90] mg/L to 139 [SD, 62] mg/L). CONCLUSION: Administration of a feeding formula enriched with fish oil was associated with decreased progression of pressure ulcers and a decrease in blood concentrations of C-reactive protein.

Enteral n-3 fatty acids and micronutrients enhance percentage of positive neutrophil and lymphocyte adhesion molecules: a potential mediator of pressure ulcer healing in critically ill patients.

n-3 Fatty acids are recognised as influencing both wound healing and immunity. We assessed the impact of a fish oil- and micronutrient-enriched formula (study formula) on the healing of pressure ulcers and on immune function in critically ill patients in an intensive care unit. A total of forty patients with pressure ulcers and receiving nutritional support were enrolled (intervention group, n 20, received study formula; and a control group, n 20, received an isoenergetic formula). Total and differential leucocyte count and percentage of adhesion molecule positive granulocyte and lymphocyte cells (CD11a, CD11b, CD18 and CD49b) were measured on days 0, 7 and 14. Percentage of positive lymphocytes for CD54, CD49b, CD49d and CD8 were also measured on days 0, 7 and 14. The state of pressure ulcers was assessed by using the pressure ulcer scale for healing tool score on days 7, 14 and 28 of treatment. No between-group differences in patient demographics, anthropometry or diagnostic class were observed. Patients who received the study formula showed significant increases in the percentage of positive CD18 and CD11a lymphocytes and of CD49b granulocytes as compared to controls (P < 0·05). While the severity of pressure ulcers was not significantly different between the two groups on admission, severity increased significantly over time for the control group (P < 0·05), but not for the study group. The present study suggests that a fish oil- and micronutrient-enriched formula may prevent worsening of pressure ulcers and that this effect may be mediated by an effect on adhesion molecule expression.

Predicting delayed pressure ulcer healing using thermography: a prospective cohort study.

OBJECTIVE: To investigate whether thermography can be used to detect latent inflammation in pressure ulcers and predict pressure ulcer prognosis in a clinical setting. METHOD: For this cohort study, we recruited 35 patients with stage II-IV pressure ulcers on the torso, who underwent thermographic assessment on discovery of their pressure ulcer. The patients were followed up for at least 3 weeks. Thermography was performed immediately after dressing removal. Pressure ulcers were classified into two groups depending on whether or not the wound site temperature was lower or higher than the periwound skin: the low temperature group and the high temperature group respectively. A generalised estimation equation was used to estimate the relative risk of delayed healing of pressure ulcers, comparing wounds with high temperatures and low temperatures. RESULTS: Of the 35 patients, 21 had 'low temperature' wounds and 14 had 'high temperature' wounds at baseline. Two patients in the high temperature group presented with overt infection, and were excluded from further analysis. Twenty-two pressure ulcers were considered to heal 'normally' (that is, the wound area reduced by 30% or more within 3 weeks) and 16 did not heal. The baseline DESIGN score (a measure of gross wound status) did not differ in any subscales between the high and low temperature groups. The relative risk for delayed healing in high temperature cases was 2.25 (95% confidence intervals; 1.13-4.47, p=0.021). Sensitivity was 0.56, specificity was 0.82, positive predictive value was 0.75, and negative predictive value was 0.67. CONCLUSION: Our results indicate that using thermography to classify pressure ulcers according to temperature could be a useful predictor of healing at 3 weeks, even though wound appearances may not differ at the point of thermographical assessment. The higher temperature in the wound site, when compared with periwound skin, may imply the presence of critical colonisation, or other factors which disturb the wound healing.

Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury.

OBJECTIVE: To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects. DESIGN: Cross-sectional study. SETTING: Clinical research unit. PARTICIPANTS: People with SCI (N=56) and different clinical presentations, and healthy, able-bodied, age-matched control subjects (N=35). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), the anti-inflammatory cytokines IL-4 and IL-10, the regulatory cytokine IL-2, the IL-1 receptor antagonist (IL-1RA), and autoantibodies against myelin-associated glycoprotein and GM(1) ganglioside (anti-GM(1)) immunoglobulin (IgG and IgM), as determined by enzyme-linked immunosorbent assay. The relationship between elevated serum cytokine levels and clinical variables was also studied. RESULTS: SCI subjects exhibited serum concentrations of IL-6, TNF-alpha, IL-1RA, and anti-GM(1) (IgG) that were greater (P<.05) than control group values. Elevated cytokine concentrations were not associated with high white blood cell counts, level of injury, or American Spinal Injury Association classification; they were evident in SCI subjects who were asymptomatic for medical complications, but were further elevated in subjects with pain, urinary tract infection (UTI), and pressure ulcers. CONCLUSIONS: Elevated levels of circulating proinflammatory cytokines and autoantibodies are present in the serum of SCI subjects without medical complications, and are further elevated in SCI subjects with neuropathic pain, UTI, or pressure ulcers, relative to healthy, able-bodied control subjects. These findings may be indicative of a protective autoimmunity, simply a consequence of occult or evident infection, or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction.

Assessment of a prognostic biochemical indicator of nutrition and inflammation for identification of pressure ulcer risk.

BACKGROUND: Pressure ulcers represent a major cost to the healthcare systems of the world but preventative measures are expensive and could be better targeted. Current risk screening mechanisms are often subjective and could be improved. AIMS: To evaluate whether a biochemical assessment tool (Prognostic Inflammatory and Nutritional Index; PINI) based on measurement of albumin, alpha1-acid glycoprotein, C-reactive protein, and prealbumin is of value in estimating the prognosis of patients with pressure ulcers of European Pressure Ulcer Advisory Panel grade 1 and above. METHODS: Serum samples were collected from patients participating in a clinical trial of a pressure ulcer preventing mattress. These were analysed for the markers listed above and the PINI calculated. PINI was then evaluated against patient outcome. RESULTS: A statistically significant difference between PINI values in patients whose pressure ulcers improved and those whose ulcers worsened was found in parametric testing, but significance was not achieved in non-parametric testing. A receiver operating characteristic plot showed the PINI was superior to chance in estimating prognosis. CONCLUSIONS: The PINI appears to offer a potential route to improving pressure ulcer risk estimation and thus allocation of scarce equipment to improve prevention.

Mini nutritional assessment and screening scores are associated with nutritional indicators in elderly people with pressure ulcers.

OBJECTIVE: To determine the association between the Mini Nutritional Assessment (MNA) or MNA Screening Form and standard indicators of nutritional status in male elders with pressure ulcers. DESIGN: Cross-sectional study. MNA and MNA Screening Form scores were related to nutritional indicators using the Pearson correlation. SUBJECTS/SETTING: Residents (79+/-1 years, N=23 men) of Veterans Affairs medical center nursing home care units with stage I to IV pressure ulcers were enrolled. MAIN OUTCOME MEASURES: Correlation coefficients were obtained from correlations between the MNA or MNA Screening Form scores and biochemical and anthropometric indices of nutritional status or measures of body composition normalized for height by dividing by height in meters(2). RESULTS: Hemoglobin (106+/-4 g/L; r=0.43, P=.0409, mean, standard error of the mean, Pearson's r, P value), hematocrit (0.32+/-0.01; r=0.44, P=.0358), body mass index (23.1+/-1.0; r=0.66, P=.0006), calf circumference (30.4+/-1.1 cm; r=0.46, P=.0286), fat-free mass index (18.3+/-0; r=0.60, P=.0063), body cell mass index (8.3+/-0.5; r=0.64, P=.0033), and fat mass index (3.7+/-0.4; r=0.50, P=.0275) positively correlated with MNA score. Serum albumin (31+/-1 g/L) and prealbumin (180+/-17 mg/L) did not correlate with MNA, but prealbumin inversely correlated with erythrocyte sedimentation rate (r=-0.52, P=.0134), a marker of inflammation. The inverse correlation between albumin and erythrocyte sedimentation rate approached statistical significance (r=-0.42, P=.0542). The MNA Screening Form showed similar correlations or lack of correlations observed with the MNA with the exception of hemoglobin and hematocrit. CONCLUSIONS: The MNA and MNA Screening Form provide advantages over using visceral proteins in screening and assessing nutritional status of elderly people with pressure ulcers.