Poly-ICLC, a multi-functional immune modulator for treating cancer.

Immunotherapies have become the first line of treatment for many cancer types. Unfortunately, only a small fraction of patients benefits from these therapies. This low rate of success can be attributed to 3 main barriers: 1) low frequency of anti-tumor specific T cells; 2) lack of infiltration of the anti-tumor specific T cells into the tumor parenchyma and 3) accumulation of highly suppressive cells in the tumor mass that inhibit the effector function of the anti-tumor specific T cells. Thus, the identification of immunomodulators that can increase the frequency and/or the infiltration of antitumor specific T cells while reducing the suppressive capacity of the tumor microenvironment is necessary to ensure the effectiveness of T cell immunotherapies. In this review, we discuss the potential of poly-ICLC as a multi-functional immune modulator for treating cancer and its impact on the 3 above mentioned barriers. We describe the unique capacity of poly-ICLC in stimulating 2 separate pattern recognition receptors, TLR3 and cytosolic MDA5 and the consequences of these activations on cytokines and chemokines production. We emphasize the role of poly-ICLC as an adjuvant in the setting of peptide-based cancer vaccines and in situ tumor vaccination by mimicking natural immune responses to infections. Finally, we summarize the impact of poly-ICLC in enhancing T infiltration into the tumor parenchyma and address the implication of this finding in the clinic.

Does the use of DACC-coated dressings improve clinical outcomes for hard to heal wounds: A systematic review.

Reports of overuse and antimicrobial resistance have fuelled some clinicians to adopt alternative wound dressings termed to be non-medicated or non-antimicrobials, which still claim antimicrobial or antibacterial activity. In this PROSPERO-registered systematic review, we evaluated the in vivo clinical evidence for the effectiveness of DACC-coated dressings in chronic, hard to heal wound-related outcomes. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Framework was adopted as the template in constructing this systematic review. The PICO format (Population [or patients], Intervention, Comparison [control], Outcome/s) was used to identify key clinical questions in determining patient outcomes under two domains (infection control and wound healing). A systematic search was performed in PubMed, OVID, Cochrane Library, clinical trial registries and data sources from independent committees. Abstracts of all studies were screened independently by two reviewers, with six further reviewers independently assessing records proceeding to full review. The authors rated the quality of evidence for each of the outcomes critical to decision making. After excluding duplicates, 748 records were screened from the databases, and 13 records were sought for full review. After full review, we excluded a further three records, leaving ten records for data extraction. Three records were narrative reviews, three systematic reviews, two prospective non-comparative before/after studies, one prospective head-to-head comparator cohort study and one retrospective head-to-head comparator cohort study. No RCTs or case versus control studies were identified. The overall quality of clinical evidence for the use of DACC-coated dressing to improve wound infection and wound healing outcomes was assessed as very low. There is an urgent unmet need to perform appropriately designed RCTs or case-control studies. The extracted data provide no clarity and have limited to no evidence to support that using a DACC-coated dressing improves wound infection or wound healing outcomes. Further, there is no evidence to suggest this therapy is either superior to standard of wound care or equivocal to topical antimicrobial agents in the management of infected hard to heal wounds.

Aquacel Ag Advantage/Ag+ Extra and Cutimed Sorbact in the management of hard-to-heal wounds: a cohort study.

OBJECTIVE: To compare Aquacel Ag Advantage/Ag+ Extra (Aquacel Ag+) (Convatec, UK) and Cutimed Sorbact (Sorbact) (Essity, US) dressings indicated for the treatment of patients with venous leg ulcers (VLUs), diabetes foot ulcers (DFUs) and pressure injuries (PIs) for clinical performance and outcomes using real-world evidence in Germany and the US. METHOD: This study was a chart audit review of patients who used either Aquacel Ag+ or Sorbact dressings in the 24 months prior to October 2022. Healthcare providers with access to electronic medical records and charts were asked to capture data via patient record forms. The quantitative data were analysed. RESULTS: Findings in Germany were comparable between Aquacel Ag+ and Sorbact with regards to wound description, management and treatment outcomes, including percent area reduction and wound closure. A difference was that a greater proportion of Sorbact patients required surgery (0% versus 11%; p=0.039). In the US, a greater proportion of wounds were worsening before dressing in the Aquacel Ag+ cohort (49% versus 34%; p=0.010). A multinomial logistic regression yielded the result that patients who received Aquacel Ag+ were 3.53 times more likely to have the wound completely healed (p=0.033). CONCLUSION: Both Aquacel Ag+ and Sorbact dressings are widely used in Germany and the US for patients with VLUs, DFUs and PIs. Our study found two important differences: patients who used Aquacel Ag+ were less likely to need further surgery in Germany; and in the US, there were significantly higher odds that wounds would completely heal with Aquacel Ag+ dressings compared to Sorbact.

Trehalose versus carboxymethylcellulose oral spray for relieving radiation-induced xerostomia in head and neck cancer patients: a randomized controlled trial.

BACKGROUND: The aim of this study was to investigate the effect of trehalose oral spray to relieve radiation-induced xerostomia on a randomized controlled trial (RCT). METHODS: Prior to RCT, the effect of trehalose (5-20%) on the epithelial growth of fetal mouse salivary gland (SG) explants was evaluated to confirm if 10% trehalose exerted the best epithelial outcomes. Participants who completed radiotherapy for head and neck cancer (HNC) treatment were enrolled in a double-blind RCT, according to inclusion and exclusion criteria as per the CONSORT statement. The experimental group (n = 35) received 10% trehalose spray, while the control group (n = 35) received carboxymethylcellulose (CMC) spray to apply intra-orally 4 times/day for 14 days. Salivary pH and unstimulated salivary flow rate were recorded pre- and post-interventions. The Xerostomia-related Quality of Life scale (XeQoLs) was filled, and scores assessed post-interventions. RESULTS: In the SG explant model, pro-acinar epithelial growth and mitosis was supported by 10% topical trehalose. As for RCT outcomes, salivary pH and unstimulated salivary flow rate were significantly improved after use of 10% trehalose spray when compared to CMC (p < 0.05). Participants reported an improvement of XeQoLs dimension scores after using trehalose or CMC oral sprays in terms of physical, pain/discomfort, and psychological dimensions (p < 0.05), but not social (p > 0.05). When comparing between CMC and trehalose sprays, XeQoLs total scores were not statistically different (p > 0.05). CONCLUSIONS: The 10% trehalose spray improved salivary pH, unstimulated salivary flow rate, and the quality-of-life dimensions linked with physical, pain/discomfort, and psychological signs. The clinical efficacy of 10% trehalose spray was equivalent with CMC-based saliva substitutes for relieving radiation-induced xerostomia; therefore, trehalose may be suggested in alternative to CMC-based oral spray.(Thai Clinical Trials Registry; https://www.thaiclinicaltrials.org/ TCTR20190817004).

Safety and antibody immune response of CHP-NY-ESO-1 vaccine combined with poly-ICLC in advanced or recurrent esophageal cancer patients.

The nanoparticle complex of cholesteryl pullulan (CHP) and NY-ESO-1 antigen protein (CHP-NY-ESO-1) presents multiple epitope peptides to MHC class I and II pathways, leading to CD8+ and CD4+ T cell responses. Poly-ICLC is a synthetic, double-stranded RNA, an agonist of toll-like receptor (TLR)-3, and a cytoplasmic receptor of melanoma differentiation-associated gene (MDA)-5. It should be a suitable immune adjuvant of cancer vaccine to overcome the inhibitory tumor microenvironment. We conducted a phase 1 clinical trial of CHP-NY-ESO-1 with poly-ICLC in patients with advanced or recurrent esophageal cancer. CHP-NY-ESO-1/poly-ICLC (µg/mg) was administered at a dose of 200/0.5 or 200/1.0 (cohorts 1 and 2, respectively) every 2 weeks for a total of six doses. The primary endpoints were safety and immune response. The secondary endpoint was tumor response. In total, 16 patients were enrolled, and six patients in each cohort completed the trial. The most common adverse event (AE) was injection site skin reaction (86.7%). No grade 3 or higher drug-related AEs were observed. No tumor responses were observed, and three patients (30%) had stable disease. The immune response was comparable between the two cohorts, and all patients (100%) achieved antibody responses with a median of 2.5 vaccinations. Comparing CHP-NY-ESO-1 alone to the poly-ICLC combination, all patients in both groups exhibited antibody responses, but the titers were higher in the combination group. In a mouse model, adding anti-PD-1 antibody to the combination of CHP-NY-ESO-1/poly-ICLC suppressed the growth of NY-ESO-1-expressing tumors. Combining the vaccine with PD-1 blockade holds promise in human trials.

Hyaluronate carboxymethylcellulose sheets for the prevention of adhesive complications: a model-based cost-utility analysis.

AIM: Clinical trials suggest that hyaluronate carboxymethylcellulose (HA/CMC) prevents adhesion-related complications after intra-abdominal surgery, but at a high upfront cost. This study evaluated the cost-effectiveness of HA/CMC for patients undergoing curative-intent open colorectal cancer surgery. METHODS: Using a Markov Monte Carlo microsimulation model, we conducted a cost-utility analysis comparing the cost-effectiveness of HA/CMC at curative-intent open colorectal cancer surgery versus standard management. We considered a scenario where HA/CMC was used at the index operation only, as well as where it was used at the index operation and any subsequent operations. The perspective was that of the third-party payer. Costs and utilities were discounted 1.5% annually, with a 1-month cycle length and 5-year time horizon. Model input data were obtained from a literature review. Outcomes included cost, quality-adjusted life-years (QALYs), small bowel obstructions (SBOs) and operations for SBO. RESULTS: Using HA/CMC at the index operation results in an incremental cost increase of CA$316 and provides 0.001 additional QALYs, for an incremental cost-effectiveness ratio of CA$310,000 per QALY compared to standard management. In our simulated cohort of 10,000 patients, HA/CMC prevented 460 SBOs and 293 surgeries for SBO. Probabilistic sensitivity analysis found that HA/CMC was cost-effective in 18.5% of iterations, at a cost-effectiveness threshold of CA$50,000 per QALY. Results of the scenario analysis where HA/CMC was used at the index operation and any subsequent operations were similar. CONCLUSIONS: Hyaluronate carboxymethylcellulose prevents adhesive bowel obstruction after open colorectal cancer surgery but is unlikely to be cost-effective given minimal long-term impact on healthcare costs and QALYs.

A tale of two alginates.

BACKGROUND: All fibrous wound dressings are considered to have the same action and value to the support of wound healing. Although clear distinction has been accepted between cotton gauze and calcium alginates, there is still no formally recognised distinction between calcium alginates and the more rapidly gelling fibre dressings. METHOD: Scientific and clinical evaluations were used to differentiate two different fibrous wound care products. One is derived from polymer extraction of algae (alginate dressings); the other has been manufactured from a uniquely patented carboxymethylation process that produces 100% carboxymethyl cellulose (CMC)-based dressings. Structural differences between these dressings were evaluated with respect to three important areas of wound care management: optimal wound moisture control; the ability to reduce risk of complication by locking away harmful components (e.g. bacteria); and reducing the overall cost of wound care by promoting more efficient use of nursing time. RESULTS: Clear differentiation was illustrated through both scientific and clinical evaluations. CONCLUSION: This study supports the potential advantages of using a technically advanced fibrous wound dressing over the traditional fibrous alginate wound care product.

Feasibility of Hyaluronate Carboxymethylcellulose-Based Bioresorbable Membrane in Two-Staged Pancreatojejunostomy.

BACKGROUND: Two-staged pancreatoduodenectomy with exteriorization of pancreatic juice is a safe procedure for high-risk patients. However, two-staged pancreatoduodenectomy requires complex re-laparotomy and adhesion removal. We analyzed whether using hyaluronate carboxymethylcellulose-based bioresorbable membrane (HCM) reduced the time required for the second operation and facilitated good fistula formation in two-staged pancreatoduodenectomy. METHODS: Between April 2011 and December 2018, data were collected from 206 consecutive patients who underwent two-staged pancreatoduodenectomy. HCM has been used for all patients since 2015. Patients for whom HCM was used (HCM group; n = 61) were compared to historical controls (before 2015) without HCM (control group; n = 145) in terms of feasibility of the second operation (operation time, adhesion grade, and complications) and optimal granulation around the external tube at the second laparotomy. RESULTS: The HCM group showed significantly shorter median operation time [105 min (30-228 min) vs. 151 min (30-331 min); p < 0.001] and smaller median blood loss [36 mL (8-118 mL) vs. 58 mL (12-355 mL); p < 0.001] for the second operation. Neither overall postoperative complication rate (p = 0.811) nor severe-grade complication rate (p = 0.857) differed significantly. Both groups showed good fistula formation, with no significant difference in rate of optimal fistula formation (HCM group, 95.1% vs. control, 95.9%; p = 0.867). CONCLUSION: HCM placement significantly improved safety and duration for the second operation, while preserving good fistula formation.

Topical treatment for facial burns.

BACKGROUND: Burn injuries are an important health problem. They occur frequently in the head and neck region. The face is the area central to a person's identity that provides our most expressive means of communication. Topical interventions are currently the cornerstone of treatment of burns to the face. OBJECTIVES: To assess the effects of topical interventions on wound healing in people with facial burns of any depth. SEARCH METHODS: In December 2019 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: Randomised controlled trials (RCTs) that evaluated the effects of topical treatment for facial burns were eligible for inclusion in this review. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction, risk of bias assessment and GRADE assessment of the certainty of the evidence. MAIN RESULTS: In this first update, we included 12 RCTs, comprising 507 participants. Most trials included adults admitted to specialised burn centres after recent burn injuries. Topical agents included antimicrobial agents (silver sulphadiazine (SSD), Aquacel-Ag, cerium-sulphadiazine, gentamicin cream, mafenide acetate cream, bacitracin), non-antimicrobial agents (Moist Exposed Burn Ointment (MEBO), saline-soaked dressings, skin substitutes (including bioengineered skin substitute (TransCyte), allograft, and xenograft (porcine Xenoderm), and miscellaneous treatments (growth hormone therapy, recombinant human granulocyte-macrophage colony-stimulating factor hydrogel (rhGMCS)), enzymatic debridement, and cream with Helix Aspersa extract). Almost all the evidence included in this review was assessed as low or very low-certainty, often because of high risk of bias due to unclear randomisation procedures (i.e. sequence generation and allocation concealment); lack of blinding of participants, providers and sometimes outcome assessors; and imprecision resulting from few participants, low event rates or both, often in single studies. Topical antimicrobial agents versus topical non-antimicrobial agents There is moderate-certainty evidence that there is probably little or no difference between antimicrobial agents and non-antimicrobial agents (SSD and MEBO) in time to complete wound healing (hazard ratio (HR) 0.84 (95% confidence interval (CI) 0.78 to 1.85, 1 study, 39 participants). Topical antimicrobial agents may make little or no difference to the proportion of wounds completely healed compared with topical non-antimicrobial agents (comparison SSD and MEBO, risk ratio (RR) 0.94, 95% CI 0.68 to 1.29; 1 study, 39 participants; low-certainty evidence). We are uncertain whether there is a difference in wound infection (comparison topical antimicrobial agent (Aquacel-Ag) and MEBO; RR 0.38, 95% CI 0.12 to 1.21; 1 study, 40 participants; very low-certainty evidence). No trials reported change in wound surface area over time or partial wound healing. There is low-certainty evidence for the secondary outcomes scar quality and patient satisfaction. Two studies assessed pain but it was incompletely reported. Topical antimicrobial agents versus other topical antimicrobial agents It is uncertain whether topical antimicrobial agents make any difference in effects as the evidence is low to very low-certainty. For primary outcomes, there is low-certainty evidence for time to partial (i.e. greater than 90%) wound healing (comparison SSD versus cerium SSD: mean difference (MD) -7.10 days, 95% CI -16.43 to 2.23; 1 study, 142 participants). There is very low-certainty evidence regarding whether topical antimicrobial agents make a difference to wound infection (RR 0.73, 95% CI 0.46 to 1.17; 1 study, 15 participants). There is low to very low-certainty evidence for the proportion of facial burns requiring surgery, pain, scar quality, adverse effects and length of hospital stay. Skin substitutes versus topical antimicrobial agents There is low-certainty evidence that a skin substitute may slightly reduce time to partial (i.e. greater than 90%) wound healing, compared with a non-specified antibacterial agent (MD -6.00 days, 95% CI -8.69 to -3.31; 1 study, 34 participants). We are uncertain whether skin substitutes in general make any other difference in effects as the evidence is very low certainty. Outcomes included wound infection, pain, scar quality, adverse effects of treatment and length of hospital stay. Single studies showed contrasting low-certainty evidence. A bioengineered skin substitute may slightly reduce procedural pain (MD -4.00, 95% CI -5.05 to -2.95; 34 participants) and background pain (MD -2.00, 95% CI -3.05 to -0.95; 34 participants) compared with an unspecified antimicrobial agent. In contrast, a biological dressing (porcine Xenoderm) might slightly increase pain in superficial burns (MD 1.20, 95% CI 0.65 to 1.75; 15 participants (30 wounds)) as well as deep partial thickness burns (MD 3.00, 95% CI 2.34 to 3.66; 10 participants (20 wounds)), compared with antimicrobial agents (Physiotulle Ag (Coloplast)). Miscellaneous treatments versus miscellaneous treatments Single studies show low to very low-certainty effects of interventions. Low-certainty evidence shows that MEBO may slightly reduce time to complete wound healing compared with saline soaked dressing (MD -1.7 days, 95% CI -3.32 to -0.08; 40 participants). In addition, a cream containing Helix Aspersa may slightly increase the proportion of wounds completely healed at 14 days compared with MEBO (RR 4.77, 95% CI 1.87 to 12.15; 43 participants). We are uncertain whether any miscellaneous treatment in the included studies makes a difference in effects for the outcomes wound infection, scar quality, pain and patient satisfaction as the evidence is low to very low-certainty. AUTHORS' CONCLUSIONS: There is mainly low to very low-certainty evidence on the effects of any topical intervention on wound healing in people with facial burns. The number of RCTs in burn care is growing, but the body of evidence is still hampered due to an insufficient number of studies that follow appropriate evidence-based standards of conducting and reporting RCTs.

Dematiaceous Fungal Colonization of the Bandage Contact Lens in a Patient Lost to Follow-up During the COVID-19 Crisis.

We report a rare case of dematiaceous fungus colonization in the therapeutic bandage contact lens (BCL), in an eye with peripheral ulcerative keratitis. Bandage contact lens removal and appropriate treatment resulted in improvement of the visual acuity and prevented the spread of fungus to the underlying ocular structures. Microbiological evaluation of the BCL showed dematiaceous fungal filaments, and the fungus was identified as Bipolaris species. In patients with pigmented plaque-like lesions, with BCL in situ, dematiaceous fungus on the undersurface of the BCL should be kept in mind. Patient education regarding the importance of frequent BCL replacement, proper ocular hygiene, and timely follow-up should be emphasized.

The Prevention of Carboxymethylcellulose on Bowel Adhesions Induced by Talc Peritonitis in Mice.

BACKGROUND: Postoperative bowel adhesions may lead to various disorders, including abdominal pain, bowel obstruction, ischemia, and necrosis. In previous reports, a dose-dependent increase in bowel adhesions was observed in talc-treated animals in comparison with control animals. Although various methods have been devised to prevent peritoneal adhesions, each of these methods has advantages and disadvantages. In this study, we have attempted to reassess the effect of a carboxymethylcellulose (CMC) solution in the reduction of peritoneal adhesions induced by an intraperitoneal injection of a talc suspension in mice. MATERIALS AND METHODS: Mice received an intraperitoneal injection of a talc suspension, followed by an injection of a CMC solution or vehicle. Two weeks after the injection, any adherent bowel mass was removed en bloc, weighed, and histologically observed. RESULTS: The administration of talc induced severe bowel adhesions. CMC treatment was unable to completely inhibit the development of bowel adhesions, but treatment did reduce their weight in a dose-dependent manner. According to a histopathologic analysis, the bowel adhesions were composed of a conglomerate of talc aggregate and granulation tissue. The conglomerate was divided into two zones: the cell-rich marginal zone and the cell-scarce central zone. The injection of CMC specifically reduced the width of the marginal zone and the number of infiltrated cells. CONCLUSIONS: This study demonstrated that CMC inhibited bowel adhesions induced by talc in mice. In addition, this is the first report on the effect of CMC on talc peritonitis accompanied by a detailed histologic examination. Our experimental model is very simple and easy to use. Therefore, it may help in the discovery of new antiadhesive agents and in the analysis of the kinetics of bowel adhesion.

Clinical efficacy of biocellulose, carboxymethyl cellulose and normal saline dressing in epidermolysis bullosa.

OBJECTIVE: To evaluate the efficacy of a biocellulose, a carboxymethyl cellulose and a normal saline wound dressing in the wound care management of epidermolysis bullosa (EB) skin wounds. METHODS: This was a single-blind, randomised controlled trial involving wounds from patients with EB. Wounds were divided into three groups: group I with biocellulose wound dressing, group II with carboxymethyl cellulose wound dressing and group III with normal saline wound dressing as a control. All dressing changes and wound parameters were recorded. Observations were conducted every three days until complete wound closure or up to one month. RESULTS: The outcomes of treatment of 36 wounds from four patients were evaluated in this study. Mean healing time in group I was seven days, eight days in group II and 14 days in group III. There were significant differences in healing times between group I and group III (p=0.0001) and between group II and III (p=0.001). The results showed a significant reduction in the percentage of wounds area on day three for each group: 51.7% in group I, 51.9% in group II, and 26% for group III. All wounds in groups I and II had healed at day 12 (100%) and at day 24 (100%) in group III. There were significant differences in the reduction of percentage wound area between group I and group III at day three (p=0.044) and day six (p=0.000), and between group II and III at day six (p=0.003). CONCLUSION: The study demonstrates that both the biocellulose and the carboxymethyl cellulose wound dressings significantly reduced percentage wound areas and complete healing times compared with the normal saline wound dressing in EB skin wounds, demonstrating they are both equally good for wound care management in EB patients.

Preparation and evaluation of bilayer films based on collagen and carboxymethylcellulose for wound therapy.

Collagen is the most abundant protein of the human body and a widely used biomaterial across sectors due to its favourable properties resulting from its physiological proximity. It plays a key role in the process of wound healing and tissue repair and is therefore used in modern wound dressings in various forms, either alone or in combination with other materials. Collagen films also offer potential applications for these purposes, because collagen has good film-forming properties and is commonly used in the food industry. The collagen films themselves, without further treatment, have weak mechanical properties, which is unsatisfactory when applied to a wound. For this reason, there is an effort to modify or to combine collagen with other materials. Therefore, the aim of our experiment was the preparation of bilayer films from collagen in combination with carboxymethylcellulose (CMC). The CMC in the bottom layer had a goal to strengthen the films, reduce the consumption of used collagen and to ensure suitable application properties. Organoleptic evaluation, pH determination, swelling properties evaluation and testing of the mechanical properties of the prepared films confirmed that the prepared films exhibited satisfactory application parameters for the wound.

Effect of PEA-OXA on neuropathic pain and functional recovery after sciatic nerve crush.

BACKGROUND: Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA. METHODS: In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function. RESULTS: Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush. CONCLUSIONS: Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain.

Outcomes of oral lichen planus and oral lichenoid lesions treated with topical corticosteroid.

OBJECTIVE: To determine corticosteroid treatment effectiveness in patients with oral lichen planus/oral lichenoid lesions (OLP/OLL). MATERIAL AND METHODS: Twenty-one patients with OLP and eighty-one patients with OLL received 0.05% clobetasol propionate (CP) or 0.05% triamcinolone acetonide (TA) in aqueous solution (AS) or orabase (OB), evaluating responses to treatment and follow-up compliance. RESULTS: Lesions were atrophic (72 of 102; 70.6%), extensive (58 of 100; 58%), producing eating difficulties (62 of 102; 60.8%), and spontaneous pain (30 of 102; 29.4%); 50 patients (49%) received CP-AS. The mean ± SD percentage of follow-ups attended was 43 ± 32%. Symptom remission was achieved in 46% of patients receiving CP-AS, 36.36% of those receiving TA-AS, 20% of those receiving CP-OB, and 25% of those receiving TA-OB. Follow-up compliance was poor in 66.7% of patients. Among 51 patients with continuous symptoms, 64.7% evidenced total remission at treatment completion; among 33 with intermittent symptoms, 73.1% had outbreaks 2-3 times/year and 51.5% controlled outbreaks with <6 corticosteroid applications. Adverse effects were observed in seven patients (6.8%) (moon face, hirsutism, capillary fragility) in induction stage, subsiding with dose; among 15 patients under maintenance treatment for >6 months, one showed hypothalamic-pituitary-adrenal (HPA) axis inhibition but not adrenal insufficiency. CONCLUSIONS: Our treatment proved highly effective and safe. Recall programs are desirable to enhance follow-up compliance.

Skin Graft Fixation Using Hydrofiber (Aquacel® Extra).

BACKGROUND: The traditional method of skin graft fixation is with tie-over bollus dressing. The use of splints in the extremities for skin graft fixation is a common practice. However, these splints are heavy and uncomfortable and contribute considerably to our overall medical waste. Hydrofiber (Aquacel Extra) has a strong fluid absorption property and fixates well to the underlying wound once applied. In this study, we used hydrofiber for fixation, avoiding the use of splints after skin grafting. METHODS: A total of 56 patients reconstructed with split-thickness skin graft that was fixated only with hydrofiber between March 2015 and March 2016 were included in this retrospective study. RESULTS: There were 44 men and 12 women with a mean age of 61 ± 18 years. The defect size ranged from 1 × 1 cm for fingertips to 30 × 12 cm for lower limb defects. The average defect size was 61 ± 78 cm. The mean skin graft take was 96% ± 6%. Because splints were not required, we saved around 48 kg of medical waste over the space of 1 year. CONCLUSIONS: The use of hydrofiber for skin graft fixation was effective and technically very simple. Splints were not required with this method, decreasing the medical waste created and increasing patient comfort. We suggest that this is an excellent alternative for skin graft fixation while at the same time decreasing our carbon footprint as surgeons.

Effects of hyaluronate-carboxymethylcellulose membranes on the clinical outcome of horses undergoing emergency exploratory celiotomy.

OBJECTIVE: To determine the influence of hyaluronate-carboxymethylcellulose (HA-CMC) membranes applied to intestinal anastomoses or enterotomies on postoperative complications after emergency exploratory celiotomy. STUDY DESIGN: Multicenter retrospective case-controlled series. ANIMALS: Adult horses (59 in the HA-CMC group and 91 controls). METHODS: Medical records from 4 referral hospitals were searched for horses ≥1 year of age, treated between 2008 and 2014 with emergency exploratory celiotomy, and surviving at least 24 hours postoperatively. Horses receiving repeat celiotomy during the same hospitalization were excluded. Horses who received HA-CMC were matched with controls who did not receive HA-CMC but had similar intestinal lesions and procedures at the same referral hospital. Postoperative complications (colic, nasogastric reflux, fever, incisional infection, and septic peritonitis), duration of hospitalization, and survival were compared between groups. Data were compared between horses by t test, Wilcoxon signed rank test, and χ2 test. RESULTS: The volume of nasogastric reflux at admission (P = .02) and the duration of administration of lidocaine after surgery (P = .02) were greater in horses with HA-CMC membranes than in controls. No difference in postoperative complications or survival was detected between groups: 48 of 59 (81%) horses treated with HA-CMC survived until discharge from the hospital compared with 80 of 91 (88%) horses in the control group (P = .27). Fifteen of 21 horses treated with HA-CMC and 30 of 43 horses in the control group survived >12 months after hospital discharge. CONCLUSION: Application of HA-CMC membranes to anastomoses or intestinal incisions did not influence postoperative complications or survival after emergency celiotomy compared with controls. CLINICAL SIGNIFICANCE: The safety and efficacy of HA-CMC membrane application to intestinal sites during colic surgery in horses is equivocal.

In vivo and ex vivo evaluation of cell-cell interactions, adhesion and migration in ocular surface of patients undergone excimer laser refractive surgery after topical therapy with different lubricant eyedrops.

PURPOSE: To investigate, in vivo by means of in vivo confocal microscopy (IVCM) and ex vivo by impression cytology, epithelial cellular damage after excimer laser refractive surgery in patients under different topical lubricant therapies. METHODS: Two hundred eyes of 100 patients, undergone bilateral excimer laser refractive surgery for medium myopic error correction [spherical equivalent refraction from -1.75 to -3.50 dioptres (D) with refractive astigmatism under -0.75 D], have been recruited. All patients received, in addition to standard therapy for refractive surgery, high weight hyaluronic acid 0.2% eyedrops in one randomly selected eye and carboxymethylcellulose 1% eyedrop in the comparator eye (control eye) 4 times daily for 90 days. Follow-up included a baseline visit and further examination 7-, 30- and 90-day intervals [clinical evaluation with Schirmer test and tear break-up time (TBUT), IVCM and impression cytology]. RESULTS: No significant difference in Schirmer test and TBUT was observed during the follow-up period in eyes under different therapies. IVCM showed an improvement of conjunctival and corneal epithelial cells quality in eye in treatment with high weight hyaluronic acid 0.2% when compared to carboxymethylcellulose. Conjunctival impression cytology demonstrated an evident positivity for CD44 in eyes treated with both treatments in all follow-up controls. ICAM1 expression showed an increasing positivity starting at 30 days that became statistically significant after 90 days of high weight hyaluronic acid 0.2% therapy (p = 0.0167). CONCLUSIONS: In vivo and in vitro results showed the effectiveness of high weight hyaluronic acid 0.2% in facilitating cell-cell interaction, migration, cell proliferation, stabilizing epithelial barrier of the ocular surface. Moreover, use of high weight hyaluronic acid in treatment of corneal tissue damage after refractive surgery, in concordance with standard topical corticosteroids and antibiotics therapy, could be effective in promoting corneal epithelial wound healing with consequent good results in clinical outcome and patients' satisfaction.

A carboxymethylcellulose-heparin combination for the prevention of surgical adhesions.

BACKGROUND: Adhesions are a major clinical problem after abdominal surgery. Despite decades of research, therapies to prevent adhesion formation are suboptimal. MATERIALS AND METHODS: We have investigated combinations of carboxymethylcellulose (CMC) and heparin at preventing surgical adhesions in two rat models of adhesion formation. The first was the well-established cecal abrasion model, and the second was a model developed in our laboratory, the avascular mesenteric knot model. This model consistently produced adhesions at the knot in 90% of experiments and causes little or no tissue injury. RESULTS: Topical administration of CMC 4% gave optimal results in the avascular knot model, but was less effective in the cecal abrasion model. This concentration of CMC was combined with a range of heparin doses between 0.5 and 160 IU/mL in the cecal abrasion model. These heparin doses, apart from the lowest (0.5 IU/mL), were effective in preventing adhesion formation in combination with CMC, as was the commercially available topical product Lipactin. The optimal dose was 30 IU/mL, that abolished adhesions, but there was little difference at doses between 2 and 160 IU. Heparin was effective in doses as low as 2 IU/mL when in combination with CMC. Heparin 160 IU/mL, but not heparin 30 IU/mL or Lipactin, significantly increased the degree of bleeding post cecal abrasion surgery. CONCLUSIONS: Topical application of tiny doses of heparin, in combination with CMC 4% gel, significantly reduces adhesion formation in experimental models. We suggest that this cheap and, as far as we know, safe intervention should be evaluated in human clinical trials.

Prevalence, Antimicrobial Susceptibility, and Clonal Diversity of Pseudomonas aeruginosa in Chronic Wounds.

PURPOSE: Our purposes in this study were to (1) identify Pseudomonas aeruginosa strains collected from swabs of chronic wounds, (2) evaluate the susceptibility of P. aeruginosa strains to various antimicrobials, (3) detect the presence of virulence factors exoenzyme S (exoS) and exoenzyme U (exoU) in P. aeruginosa strains, and (4) evaluate wound colonization by P. aeruginosa via pulsed-field gel electrophoresis (PFGE). DESIGN: Descriptive research using a quantitative approach. SAMPLE AND SETTING: Swabs from 43 adults with chronic wounds treated in an outpatient setting in Niterói City, Brazil, were included using convenience sampling. METHODS: Swabs were collected at 2 points during treatment, 30 to 45 days apart. P. aeruginosa isolates were identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Antimicrobial susceptibility testing was performed using the disk diffusion method. The presence of exoS and exoU genes was evaluated using polymerase chain reaction. Genotyping diversity was determined through PFGE. RESULTS: Forty-eight P. aeruginosa isolates were detected in chronic wounds, and 3 were multidrug resistant (6%). Resistance to aztreonam and ciprofloxacin was observed in 48% and 27% of isolates, respectively. The presence of the exoS gene was verified in 54% of isolates, and 27% were positive for the exoU gene. In most wounds, P. aeruginosa strains had the same genetic characteristics at the 2 time points analyzed, indicating that the wound beds remained colonized. CONCLUSIONS: P. aeruginosa was present in 75% of tested chronic wound samples, and the same clones persisted for more than 1 month. In addition, most bacteria contained virulence genes that were associated with high potential to establish infection. The use of silver in chronic wounds may be associated with multidrug resistance in P. aeruginosa; therefore, it is important to avoid colonization by these bacteria.