Alginate-amphotericin B nanocomplexes covered by nanocrystals from bacterial cellulose: physico-chemical characterization and in vitro toxicity.

Nanocomplexes systems made up natural poylymers have pharmacotechnical advantages such as increase of water solubility and a decrease of drugs toxicity. Amphotericin B (AmB) is a drug apply as anti-leishmanial and anti-fungal, however it has low water solubility and high toxicity, limiting its therapeutic application. With this in mind, the present study aimed to produce nanocomplexes composed by alginate (Alg), a natural polymer, with AmB covered by nanocrystals from bacterial cellulose (CNC). For this reason, the nanocomplexes were produced utilizing sodium alginate, amphotericin B in a borate buffer (pH 11.0). The CNC was obtained by enzymatic hydrolysis of the bacterial cellulose. To CNC cover the nanocomplexes 1 ml of the nanocomplexes was added into 1 ml of 0.01% CNC suspension. The results showed an ionic adsorption of the CNC into the Alg-AmB nanocomplexes surface. This phenomena was confirmed by an increase in the particle size and PDI decrease. Besides, nanocomplexes samples covered by CNC showed uniformity. The amorphous inclusion of AmB complex into the polysaccharide chain network in both formulations. AmB in the nanocomplexes was in supper-aggregated form and showed good biocompatibility, being significantly less cytotoxic in vitro against kidney cells and significantly less hemolytic compared to the free-drug. The in vitro toxicity results indicated the Alg-AmB nanocomplexes can be considered a non-toxic alternative to improve the AmB therapeutic effect. All process to obtain nanocomplexes and it coat was conduce without organic solvents, can be considered a green process, and allowed to obtain water soluble particles. Furthermore, CNC covering the nanocomplexes brought additional protection to the system can contribut advancement in the pharmaceutical.

Topical microbicides for preventing sexually transmitted infections.

BACKGROUND: This is a updated version of our Cochrane Review published in Issue 6, 2012. Sexually-transmitted infections (STIs) continue to rise worldwide, imposing an enormous morbidity and mortality burden. Effective prevention strategies, including microbicides, are needed to achieve the goals of the World Heath Organization (WHO) global strategy for the prevention and control of these infections. OBJECTIVES: To determine the effectiveness and safety of topical microbicides for preventing acquisition of STIs, including HIV. SEARCH METHODS: We undertook a comprehensive search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CLIB, Web of Science, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and reference lists of relevant articles up to August 2020. In addition, we contacted relevant organisations and experts. SELECTION CRITERIA: We included randomised controlled trials of vaginal microbicides compared to placebo (except for nonoxynol-9 because it is covered in related Cochrane Reviews). Eligible participants were sexually-active non-pregnant, WSM and MSM, who had no laboratory confirmed STIs. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies, extracted data, and assessed risks of bias in duplicate, resolving differences by consensus. We conducted a fixed-effect meta-analysis, stratified by type of microbicide, and assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included eight trials from the earlier version of the review and four new trials, i.e. a total of 12 trials with 32,464 participants (all WSM). We did not find any eligible study that enrolled MSM or reported fungal STI as an outcome. We have no study awaiting assessment. All 12 trials were conducted in sub-Saharan Africa, with one having a study site in the USA, and another having a site in India. Vaginal microbicides tested were BufferGel and PRO 2000 (1 trial, 3101 women), Carraguard (1 trial, 6202 women), cellulose sulphate (2 trials, 3069 women), dapivirine (2 trials, 4588 women), PRO 2000 (1 trial, 9385 women), C31G (SAVVY) (2 trials, 4295 women), and tenofovir (3 trials, 4958 women). All microbicides were compared to placebo and all trials had low risk of bias. Dapivirine probably reduces the risk of acquiring HIV infection: risk ratio (RR) 0.71, (95% confidence interval (CI) 0.57 to 0.89, I2 = 0%, 2 trials, 4588 women; moderate-certainty evidence). The other microbicides may result in little to no difference in the risk of acquiring HIV (low-certainty evidence); including tenofovir (RR 0.83, 95% CI 0.68 to 1.02, cellulose sulphate (RR 1.20, 95% CI 0.74 to 1.95, BufferGel (RR 1.05, 95% CI 0.73 to 1.52), Carraguard (RR 0.89, 95% CI 0.71 to 1.11), PRO 2000 (RR 0.93, 95% CI 0.77 to 1.14), and SAVVY (RR 1.38, 95% CI 0.79 to 2.41). Existing evidence suggests that cellulose sulphate (RR 0.99, 95% CI 0.37 to 2.62, 1 trial, 1425 women), and PRO 2000 (RR 0.95, 95% CI 0.73 to 1.23) may result in little to no difference in the risk of getting herpes simplex virus type 2 infection (low-certainty evidence). Two studies reported data on tenofovir's effect on this virus. One suggested that tenofovir may reduce the risk (RR 0.55, 95% CI 0.36 to 0.82; 224 participants) while the other did not find evidence of an effect (RR 0.94, 95% CI 0.85 to 1.03; 1003 participants). We have not reported the pooled result because of substantial heterogeneity of effect between the two studies (l2 = 85%). The evidence also suggests that dapivirine (RR 1.70, 95% CI 0.63 to 4.59), tenofovir (RR 1.27, 95% CI 0.58 to 2.78), cellulose sulphate (RR 0.69, 95% CI 0.26 to 1.81), and (Carraguard (RR 1.07, 95% CI 0.75 to 1.52) may have little or no effect on the risk of acquiring syphilis (low-certainty evidence). In addition, dapivirine (RR 0.97, 95% CI 0.89 to 1.07), tenofovir (RR 0.90, 95% CI 0.71 to 1.13), cellulose sulphate (RR 0.70, 95% CI 0.49 to 0.99), BufferGel (RR 0.97, 95% CI 0.65 to 1.45), Carraguard (RR 0.96, 95% CI 0.83 to 1.12), and PRO 2000 (RR 1.01, 95% CI 0.84 to 1.22) may result in little to no difference in the risk of acquiring chlamydia infection (low-certainty evidence). The evidence also suggests that current topical microbicides may not have an effect on the risk of acquiring gonorrhoea, condyloma acuminatum, trichomoniasis, or human papillomavirus infection (low-certainty evidence). Microbicide use in the 12 trials, compared to placebo, did not lead to any difference in adverse event rates. No study reported on acceptability of the intervention.  AUTHORS' CONCLUSIONS: Current evidence shows that vaginal dapivirine microbicide probably reduces HIV acquisition in women who have sex with men. Other types of vaginal microbicides have not shown evidence of an effect on acquisition of STIs, including HIV. Further research should continue on the development and testing of new microbicides.

Injection of oral medication into the skin confirmed by infrared spectroscopy.

"Skin popping" refers to the practice of injecting drugs, most commonly heroin, subcutaneously or into granulation tissue. Pharmaceutical tablets meant for oral consumption are modified into solutions for injection. Excipients-inactive substances that serve as vehicles for medication-are often not filtered out before injection and result in abscess formation, granulomatous inflammation, and scarring. Common excipients used in the production of pharmaceutical tablets include starch, microcrystalline cellulose, magnesium stearate, silica, and polyvinylpyrrolidone (PVP). Identification of these exogenous materials is valuable in confirming the diagnosis of skin popping, especially when patients may not be forthcoming about their drug use. We present a case of subcutaneous oral medication injection in which PVP and cellulose were identified by Fourier transform infrared spectroscopy. Considering the variable cutaneous manifestations of injection drug abuse, recognition of histopathologic and chemical characteristics of exogenous material from oral medications is helpful for diagnosis and intervention.

Subcision™ plus poly-l-lactic acid for the treatment of cellulite associated to flaccidity in the buttocks and thighs.

BACKGROUND: There is a growing demand for procedures to treat cellulite. Subcision™ is widely used for cellulite correction, and injectable poly-L-lactic acid (PLLA) has been shown to be an effective option for various body conditions. AIMS: Present the results of combining Subcision™ plus PLLA, in the same session, in patients with cellulite and flaccidity. PATIENTS/METHODS: Twenty-four women underwent Subcision™ followed by PLLA injections. An expert panel of dermatologists evaluated before and after photographs according to Global Aesthetic Improvement Scale (GAIS). Patients also answered a satisfaction questionnaire. RESULTS: The author describes the results, as well as number of sessions and dose used. The most frequent GAIS score was "great improvement." No nodules or granulomas appeared in the treated areas. CONCLUSION: The combination of Subcision™ plus PLLA, in the same treatment session, promotes safe and desirable results for cellulite associated with flaccidity.

Study of Biocompatibility of Membranes in Online Hemodiafiltration.

BACKGROUND: The biocompatibility of dialysis membranes is a determining factor in avoiding chronic microinflammation in patients under haemodialysis. Lower biocompatibility has been related to increased inflammatory status, which is known to be associated with cardiovascular events. Classically, cellulose membranes have been considered bioincompatible. A new-generation of asymmetric cellulose triacetate (CTA) membranes allows the performance of high convective transport techniques, but there have been no studies of their biocompatibility. The aim of the present study was to analyze and compare the biocompatibility characteristics of 4 membranes, including CTA, in online hemodiafiltration (OL-HDF) patients. METHODS: We included 15 patients in -OL-HDF. After a 2-week washout period with helixone membrane, each patient was treated with the 4 membranes (polyamide, polynephron, helixone and CTA) for 4 weeks in a randomized order. The other dialysis parameters were kept stable throughout the study. We studied changes in markers of the activation of the complement system, monocytes, platelets, and adhesion molecules with the 4 membranes, as well as inflammatory parameters. RESULTS: Biocompatibility was similar among the membranes. There were no sustained differences in complement activation, measured by C3a and C5a levels, or in platelet activation, determined by levels of P-selectin and platelet-derived microparticles (CD41a+). No differences were observed in activated monocyte levels (CD14+/CD16+) or in plasma levels of interleukin (IL)-1, IL-6, IL-10 or high-sensitivity C-reactive protein, although tumour necrosis factor-α levels decreased when the patients were dialyzed with CTA. No significant differences were found in markers of endothelial damage, assessed by levels of plasminogen activator inhibitor-1 and adhesion molecules (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1). CONCLUSION: The 4 membranes evaluated in this study in stable patients on OL-HDF, including the new-generation CTA, show similar biocompatibility with the methods applied.

Cellulose-Derived Absorbable Hemostatic Product as a Risk Factor for Mediastinitis after Cardiac Surgery.

Background: We describe the management and control of an outbreak of mediastinitis in a cardiac surgery department. Method: We performed a retrospective cohort study of 87 patients who underwent coronary artery bypass grafting (CABG), valve replacement, or both during a five-month period with a higher than normal number of cases of post-operative mediastinitis. In addition to medical records review, a survey was conducted among surgeons to estimate the frequency of cellulose-derived absorbable hemostatic (CDAH) use. Results: Eleven patients (12.5%) developed mediastinitis during the period. None of them died, and the course of the infections was benign. No differences were found between the infected and non-infected patients regarding clinical or demographic characteristics. The rate of infection by surgeon ranged from 0 to 21.4%. (p = 0.38). We found a significant linear relation between the frequency of CDAH use and the risk of infection, from 3.3% to 22.6% (p = 0.024). Cultures of unused CDAHs were negative. Cessation of product use led to no new cases for the following year and to a mediastinitis rate <1% for the following 24 months. Conclusion: We identified a cluster of undesired clinical outcomes compatible with mediastinitis that added morbidity and associated cost, but not deaths, related to the use of CDAH as a hemostatic. These data suggest keeping the use of CDAH in cardiothoracic surgery to a minimum.

Parenteral administration of oral medications in lung transplant recipients: An underrecognized problem.

Microcrystalline cellulose (MCC) is an insoluble material commonly used as a binder and filler in oral medications. Identification of pulmonary intravascular deposition of MCC in transbronchial biopsies from lung transplant (LT) recipients following parenteral injection of oral medications has only been reported once. A search of our surgical pathology electronic database was performed from January 1, 2000 to November 1, 2017 using the text "transplant transbronchial." The diagnosis field for all cases retrieved was then searched for the text "cellulose." These cases were queried for patient demographics and outcomes. Between January 1, 2000 and November 1, 2017, 1558 lung transplants were performed in 1476 individual patients at our institution; 12 were identified to have MCC in their lung tissue. Patients with MCC identified on biopsies were more likely to be transplanted for cystic fibrosis versus other indications and younger versus older. MCC identified in 2 of our cases was favored to be donor derived. Of the 12 patients, 6 (50%) are deceased. MCC within the pulmonary vasculature may be an indicator of increased complications, mortality, or shortened survival in LT recipients. Detecting intravascular MCC and distinguishing it from aspirated foreign material can be challenging. Awareness of the differential diagnosis for pulmonary foreign material is of paramount importance for the pathologist.

Effect of Cellulose Powder on Human Nasal Epithelial Cell Activity and Ciliary Beat Frequency.

BACKGROUND: Cellulose powder (CP) has been reported as a safe and effective complementary treatment for allergic rhinitis (AR). Currently, CP has gained increasing application for clinical management worldwide, particularly in China. However, studies focusing on the effect of CP on normal human nasal epithelial cells (hNECs) and ciliary function are lacking. Here, we aimed to explore the adverse effects of CP on the activity and ciliary function of hNECs. METHODS: We biopsied ethmoid sinus or middle turbinate tissues during surgical resection from control subjects who underwent endoscopic sinus surgery for diseases other than AR. Cells were isolated and passaged, followed by differentiation in an air-liquid interface (ALI). Flow cytometry and cell viability test (cell counting kit-8) were performed to detect the cytotoxicity of CP (effects on cell proliferation) on normal hNECs. By using the ALI culture model, we investigated the effects of CP on ciliary beat frequency (CBF). RESULTS: There was a significant reduction in hNEC count at high concentrations of CP (2.5 mg/mL) at days 3 and 7 (both p < 0.05). As the concentration increased, cell death increased progressively from day 3 to day 7. However, these effects were not evident at low concentrations (0.25 mg/mL, p > 0.05). High-dose CP (2.5 mg) significantly reduced the CBF (p < 0.05). At lower concentrations (0.25-2.5 mg/mL), CP initially increased but subsequently reduced the CBF of hNECs compared with control group. CONCLUSIONS: Cytotoxicity and the suppression of ciliary beat at high concentrations justify more prudent use of CP for the management of AR.

Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenic Escherichia coli to bladder epithelial cells.

Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infections, employing numerous molecular strategies to contribute to adhesion, colonization, and persistence in the bladder niche. Identifying strategies to prevent adhesion and colonization is a promising approach to inhibit bacterial pathogenesis and to help preserve the efficacy of available antibiotics. This approach requires an improved understanding of the molecular determinants of adhesion to the bladder urothelium. We designed experiments using a custom-built live cell monolayer rheometer (LCMR) to quantitatively measure individual and combined contributions of bacterial cell surface structures [type 1 pili, curli, and phosphoethanolamine (pEtN) cellulose] to bladder cell adhesion. Using the UPEC strain UTI89, isogenic mutants, and controlled conditions for the differential production of cell surface structures, we discovered that curli can promote stronger adhesive interactions with bladder cells than type 1 pili. Moreover, the coproduction of curli and pEtN cellulose enhanced adhesion. The LCMR enables the evaluation of adhesion under high-shear conditions to reveal this role for pEtN cellulose which escaped detection using conventional tissue culture adhesion assays. Together with complementary biochemical experiments, the results support a model wherein cellulose serves a mortar-like function to promote curli association with and around the bacterial cell surface, resulting in increased bacterial adhesion strength at the bladder cell surface.

Fibrous nanocellulose, crystalline nanocellulose, carbon nanotubes, and crocidolite asbestos elicit disparate immune responses upon pharyngeal aspiration in mice.

With the rapid development of synthetic alternatives to mineral fibers, their possible effects on the environment and human health have become recognized as important issues worldwide. This study investigated effects of four fibrous materials, i.e. nanofibrillar/nanocrystalline celluloses (NCF and CNC), single-walled carbon nanotubes (CNTs), and crocidolite asbestos (ASB), on pulmonary inflammation and immune responses found in the lungs, as well as the effects on spleen and peripheral blood immune cell subsets. BALB/c mice were given NCF, CNC, CNT, and ASB on Day 1 by oropharyngeal aspiration. At 14 days post-exposure, the animals were evaluated. Total cell number, mononuclear phagocytes, polymorphonuclear leukocytes, lymphocytes, and LDH levels were significantly increased in ASB and CNT-exposed mice. Expression of cytokines and chemokines in bronchoalveolar lavage (BAL) was quite different in mice exposed to four particle types, as well as expression of antigen presentation-related surface proteins on BAL cells. The results revealed that pulmonary exposure to fibrous materials led to discrete local immune cell polarization patterns with a TH2-like response caused by ASB and TH1-like immune reaction to NCF, while CNT and CNC caused non-classical or non-uniform responses. These alterations in immune response following pulmonary exposure should be taken into account when testing the applicability of new nanosized materials with fibrous morphology.

Positive staining for cellulose in oral pulse granuloma.

OBJECTIVE: Oral pulse granuloma (OPG) is an oral inflammatory lesion characterized by the presence of hyaline rings with numerous multinucleated giant cells. The etiopathogenesis of this lesion is thus far unclear, as is the composition of the hyaline rings. Our aim was to investigate whether the hyaline rings contain cellulose. STUDY DESIGN: Using a newly developed staining method for cellulose, we studied 18 histologic samples diagnosed as OPG, in addition to 3 samples originally diagnosed as "normal" foreign body reactions. In our study, visualization of cellulose is based on its specific binding to the carbohydrate binding module of ß-1,4-glycanase. RESULTS: All samples diagnosed as OPG were positive for cellulose staining localized in hyaline rings. In addition, 1 lesion (of 3), first diagnosed as a foreign body reaction without the presence of hyaline rings, was positive for cellulose by horseradish peroxidase staining. CONCLUSIONS: We show for the first time that cellulose is present in OPG lesions, indicating that cellulose might be the initial cause of formation of these lesions.

[Changes in endocrine profile of workers in pulp and paper plant.]

Examination covered 245 individuals and included characteristics of endocrine state of pulp and paper plant workers over 2011-2012, in comparison with data from 1990, as well as comparison with reference groups of male workers with no contact with chemical'industry in Arkhangelsk. Findings are both in main and reference groups general decrease in levels of cortisol, thyroxin;progesterone, testosterone, insulin, somatotropin and increased serum level of estradiol. With that, inside both groups, reliable tendencies to increased levels of cortisol, thyroxin, insulin, SSH and lower concentration of progesterone in the pulp and paper plant workers vs. the reference group members. Positive tendency was absence of abnormal concentrations of insulin, SSH and lower frequency of high cortisol levels in the pulp and paper plant workers nowadays.

Neuropathic Pain Following Poly-L-Lactic Acid (Sculptra) Injection.

Injectable fillers have become a prevalent means of facial rejuvenation and volume expansion. While typically well tolerated, serious complications have been reported. The authors present a case in which an otherwise healthy female with a history of multiple filler injections including poly-L-lactic acid, developed 3 weeks of neuropathic pain in the left temporal fossa following injection. To the best of the authors knowledge, neuropathic pain has not been reported as a complication following poly-L-lactic acid injection. The patient was treated with an injection of steroid and long-acting anesthetic with resolution of symptoms.

Granuloma Due to Oxidized Regenerated Cellulose in an Aged Rhesus Macaque (Macaca mulatta).

Bioabsorbable hemostatic agents such as oxidized regenerated cellulose are widely used to control intraoperative diffuse capillary bleeding. Compared with electrocautery or ligation, oxidized regenerated cellulose has the advantage of controlling bleeding without occluding the vessel lumen or causing thermal injuries to adjacent tissue. Although the manufacturer recommends removal of the material once hemostasis is achieved, oxidized regenerated cellulose is a bioabsorbable hemostatic agent and is often left in the surgical bed to prevent subsequent bleeding after surgical closure. However, noninvasive imaging techniques have revealed granulomatous foreign-body reactions that mimic infection or tumor recurrence. We present a case report of sterile peritonitis and granuloma formation secondary to the presence of oxidized regenerated cellulose after intestinal resection to excise a colonic adenocarcinoma in an aged rhesus macaque.

Postoperative Granulomas at Liposuction Incision Sites.

Since most liposuction incisions heal uneventfully, difficult healing in such incisions must be investigated. In the cases of two gynecomastia liposuction patients in which a water-based lubricating gel was used on the liposuction incisions, the incisions failed to heal. For both patients, workup uncovered palisading granulomas at the lateral inframammary fold incision sites several months after otherwise successful surgeries. These two cases are presented and the previous literature is reviewed, with consideration given to the etiology and prevention of such granulomas. LEVEL OF EVIDENCE 5: Risk.

Fatal foreign-body granulomatous pulmonary embolization due to microcrystalline cellulose in a patient receiving total parenteral nutrition: all crystals are not what they seem.

Pulmonary foreign-body granulomatous embolization has been described secondary to crystal precipitation in total parenteral nutrition (TPN) as well as when pharmaceutical tablets are crushed and injected intravenously. Extensive granulomatous embolization may cause pulmonary hypertension and death due to acute cor pulmonale. We report the case of a 34-year old woman who had been receiving TPN post-operatively secondary to complications of a paraesophageal hernia repair. During and following receiving TPN, she experienced episodes of hypoxia, tachycardia, fever, and hypotension. Computed tomography scans of the thorax showed centrilobular nodules, tree-in-bud and ground-glass opacities, as well as findings of pulmonary hypertension. Following an episode of hypoxia she was found unresponsive and died despite resuscitative efforts. Microscopic examination of the lungs following post-mortem examination revealed occlusive granulomatous inflammation of the pulmonary arterial vasculature by crystalline material. The morphologic and histochemical patterns of the crystals were suggestive of microcrystalline cellulose, a finding that was confirmed by energy dispersive X-spectroscopy and infrared spectroscopy. Ancillary tests did not support that the crystalline material was the result of TPN precipitation. Foreign-body granulomatous embolization leading to acute core pulmonale may occur as a complication of both intravenous injection of oral medications as well as of TPN crystallization. The source of crystalline material may be difficult to discern based solely on morphological assessment or by histochemical staining. Ancillary studies such as energy dispersive X-spectroscopy or infrared spectroscopy should be performed to definitively discern the two entities.

Genotoxic and immunotoxic effects of cellulose nanocrystals in vitro.

Nanocellulosics are among the most promising innovations for a wide-variety of applications in materials science. Although nanocellulose is presently produced only on a small scale, its possible toxic effects should be investigated at this early stage. The aim of the present study was to examine the potential genotoxicity and immunotoxicity of two celluloses in vitro - cellulose nanocrystals (CNC; mean fibril length 135 nm, mean width 7.3 nm) and a commercially available microcrystalline (non-nanoscale) cellulose (MCC; particle size ∼50 µm). Both celluloses showed 55% cytotoxicity at approximately 100 µg/ml after 4-h, 24-h, and 48-h treatment of human bronchial epithelial BEAS 2B cells, as determined by luminometric detection of ATP and cell count (dead cells identified by propidium iodide). Neither of the materials was able to induce micronuclei (MN) in binucleate or mononucleate BEAS 2B cells after a 48-h treatment (2.5-100 µg/ml). In human monocyte-derived macrophages, MCC induced a release (measured by enzyme-linked immunosorbent assay; ELISA) of the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and (after lipopolysaccharide-priming) interleukin 1ß (IL-1ß) after a 6-h exposure to a dose of 300 µg/ml, but CNC (30-300 µg/ml) did not. In conclusion, our results show that nanosized CNC is neither genotoxic nor immunotoxic under the conditions tested, whereas non-nanosized MCC is able to induce an inflammatory response. More studies are needed, especially in vivo, to further assess if CNC and other nanocelluloses induce secondary genotoxic effects mediated by inflammation.

Reduction of Leg Pain by Oxiplex Gel After Lumbar Discectomy in Patients With Predominant Leg Pain and Elevated Levels of Lower Back Pain: A Prospective, Randomized, Blinded, Multicenter Clinical Study.

STUDY DESIGN: A prospective, randomized, blinded, multicenter clinical study. OBJECTIVE: To evaluate carboxymethylcellulose/polyethylene oxide gel (Oxiplex) in improving clinical outcomes in subjects having predominant leg pain and elevated low back pain undergoing first-time lumbar discectomy for disk herniation. SUMMARY OF BACKGROUND DATA: Clinical studies in the United States and Italy found that Oxiplex reduced leg pain after decompression surgery. METHODS: A total of 68 subjects with herniated lumbar disk were enrolled and randomized into treatment (surgery plus gel) or surgery-only control groups. A prospective statistical analysis assessed the effect of gel in the severe back pain subgroup (prespecified as greater than or equal to median baseline back pain of the population studied). All subjects except 2 controls lost to follow-up completed the study. Preoperative and postoperative visual analogue scale leg pain scores were analyzed and compared between groups at 60 days after surgery. RESULTS: There were no serious adverse events or neurological safety concerns reported in any patients. Gel-treated patients had statistically significantly lower visual analogue scale leg pain scores at study end compared with controls (P=0.0240), representing a 21% additional reduction in leg pain compared with surgery alone in the severe baseline back pain subgroup (P=0.0240). The proportion of subgroup patients experiencing zero leg pain at study end was significantly higher in the gel treatment group (60%) than in the control group (23%) (P=0.0411). CONCLUSIONS: The data from this study confirm and extend results of 2 previous studies in Italy and the United States that reported statistically significantly greater reductions in leg pain in gel-treated patients with severe preoperative low back pain compared with patients who only underwent decompression surgery.