Mannuronic Acid in Low-Risk and Intermediate-1-Risk Myelodysplastic Syndromes.

The discovery of hematologic improvement and bone marrow modification by the drug ß-D mannuronic acid (M2000) during treatment of rheumatoid arthritis in phase 1/2/3 clinical trials prompted us to design a new trial to target hematologic deficits in myelodysplastic syndromes (MDS). In this open-label, randomized phase 2 clinical trial, the potential effect and tolerability of drug M2000 was assessed in patients with low- and intermediate-1-risk MDS. The primary efficacy end point was hematologic improvement after 12 weeks of ß-D-mannuronic acid therapy. Among 34 enrolled patients, half received their conventional therapy plus ß-D-mannuronic acid, and the other half received only conventional drugs. In the conventional + ß-D mannuronic acid treatment group, hematologic improvement and development of transfusion independence and/or reduction in transfusion requirements were seen in 12 patients (92.3%) and 1 patient (7.7%), respectively. Moreover, 5 patients (38.5%), 2 patients (15.4%), and 1 patient (7.7%) in the ß-D-mannuronic acid-treated group showed hematologic improvement of the major parameters of erythroid, neutrophil, and platelet responses, respectively, based on the International Working Group criteria), whereas in the conventional treatment group as control, no hematologic improvements including erythroid, neutrophil, and platelet response was seen. In this trial, the addition of ß-D mannuronic acid to conventional treatment showed promising results in MDS patients with low and intermediate-1 risk with effects on hematologic improvements without significant adverse effect.

The safety and efficacy of Guluronic acid (G2013) in ankylosing spondylitis: A randomized controlled parallel clinical trial.

BACKGROUND: To assess the therapeutic efficacy, safety and tolerability of Guluronic acid (G2013) in patients with ankylosing spondylitis (AS) patients. METHODS: This investigation was a 12-week randomized, placebo-controlled, phase I/II clinical trial involving 75 AS patients that were randomly divided into 3 groups: 25 as placebo, 25 Guluronic acid and 25 naproxen groups. Patients who had AS with active disease at baseline according to the modified New York criteria were considered for this trial. The primary consequence measure was the Appraisement of Spondyloarthritis International Society (ASAS) 20 response-rate at week 12. RESULTS: There were no statistically significant differences between groups at the entry. ASAS20 response at week 12 was achieved (60.8%) in patients receiving Guluronic acid compared with - (68.4% of) - patients in the naproxen group (p > 0.05) and (21.0%) of patients in the placebo group. In comparison with the placebo group from the baseline to week 12, patients who received Guluronic acid and naproxen showed significantly greater improvement in all secondary endpoints. Moreover, Guluronic acid decreased some inflammatory parameters more dramatically than naproxen and placebo group. Patients in the naproxen group had more incidence of gastrointestinal and others adverse events in comparison with Guluronic acid and placebo groups. CONCLUSION: The present research indicated that Guluronic acid and naproxen are similar in terms of efficacy. However, Guluronic acid had more notable safety characteristics identifying information than naproxen. Accordingly, it is proposed that Guluronic acid could be appropriate for management of AS. Clinical trial identifier; IRCT2016091813739N4.

A randomized, controlled, phase II clinical trial of ß-D-mannuronic acid (M2000) in pre-surgical breast cancer patients at early stage (T1-T2).

Following the potent efficacy of ß-D-Mannuronic acid in a breast cancer murine model, we evaluated the efficacy of this novel non-steroidal anti-inflammatory drug in breast cancer patients in the present clinical trial. The study was an 8-week randomized, controlled, phase II clinical trial (IRCT: 2017012213739N7 (in 48 pre-surgical breast cancer patients. Patients who had breast cancer at early stage, with invasive ductal carcinoma, were placed on a waiting-list for surgery and were allocated to the study. ß-D-Mannuronic was administrated at a dose of two capsules (1000 mg/d) orally during a period of 8 weeks. The end point of this study was when the patients were admitted for surgery. Moreover, the patients' well-being status was followed up on for safety. There were no statistically significant differences between treatment and non-treatment groups at baseline. ß-D-Mannuronic acid therapy, from 20 patients, showed that in one patient (5%) tumour size was decreased; in five patients (25%) tumour growth was stopped; and in 14 patients (70%) the growth rate in the treatment group did not show significant change, compared to the non-treatment group. Evaluation of two tumour markers (carcinoembryonic antigen and cancer antigen 15-3) showed that there was no significant difference between before and after treatment. Although the use of some non-steroidal anti-inflammatory drugs in a long time period has shown a prophylactic effect in breast cancer, their therapeutic efficacy in a short time period is unknown, whereas treatment with ß-D-Mannuronic acid during 8 weeks could show 30% therapeutic effects in pre-surgical breast cancer patients.

Modification of Sexual Hormones in Rheumatoid Arthritis Patients by M2000 (ß-D-mannuronic Acid) as a Novel NSAID with Immunosuppressive Property.

BACKGROUND: Based on in-vitro, in-vivo and human studies, the ß-D-mannuronic acid (M2000) has been introduced as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive properties. OBJECTIVE: This study aimed to evaluate the efficacy of this drug on serum level of sex hormones (Estradiol, Progesterone, and DHEAS) in rheumatoid arthritis (RA) patients. METHODS: The present research was performed on 10 RA patients who had an inadequate response to conventional treatments (clinical trial identifier: IRCT2014011213739N2). During this trial, the patients were permitted to continue the conventional therapy along with adding M2000 orally at a dose of 500 mg twice daily for 12 weeks. Serum samples were collected in a normal group, patient group (at baseline) and treatment group (after 12 weeks). The samples were tested for evaluating the serum level of Estradiol, Progesterone, and DHEAS using chemiluminescent microparticle immunoassay. RESULTS: Data showed that the serum level of estradiol was reduced (both in men and women) during the treatment with M2000 (after 12 weeks), but there was no significant difference in the non-treated group with M2000 (p > 0.05). In addition, the serum level of progesterone and DHEAS significantly increased following the 12-week administration of M2000 in both male and female patients, compared to the non-treated group with M2000 (p < 0.001, p < 0.05, p < 0.05, p < 0.01, respectively). CONCLUSION: The present research showed that the sex hormones might be modified by M2000 therapy in RA patients by increasing the serum level of progesterone and DHEAS compared to healthy individuals.

A phase I/II randomized, controlled, clinical trial for assessment of the efficacy and safety of ß-D-mannuronic acid in rheumatoid arthritis patients.

BACKGROUND: Following the potent efficacy of ß-D-mannuronic acid (M2000) in phase I/II trial in ankylosing spondylitis patients, the present clinical trial was conducted to evaluate the efficacy, safety, and tolerability of this novel drug in rheumatoid arthritis (RA) patients who had inadequate response to conventional therapy. METHOD: The study was a 12-week randomized, controlled, phase I/II clinical trial with two treatment arms: M2000 and conventional treatment. Patients who had RA according to the modified American College of Rheumatology (ACR) criteria, with active disease at baseline also inadequate response to conventional therapy, were enrolled in this study. M2000 was administrated at a dose of two capsules (500 mg) per day orally during a period of 12 weeks. The primary endpoint was the proportion of patients fulfilling the ACR 20% improvement criteria after 12 weeks of M2000 therapy. Moreover, the patients were also followed up for safety. RESULTS: There were no statistically significant differences between treatment and conventional groups at baseline characteristics. The ACR20 response rate was significantly higher among M2000-treated patients than conventional-treated control, so that 74% of patients in treatment group showed an ACR20 response after 12 weeks of M2000 therapy (74 versus 16%; P = 0.011). 10% of M2000-treated patients and 57.1% of conventional-treated patient's adverse events occurred during this study. CONCLUSION: Treatment with M2000 in combination with conventional therapy showed a significantly superior efficacy along with a high safety profile compared to conventional-treated patients. Thereby, M2000 might be suggested as a suitable option in the treatment of RA.

Randomized controlled trial of steroid-soaked absorbable calcium alginate nasal packing following endoscopic sinus surgery.

OBJECTIVES/HYPOTHESIS: To evaluate the potential efficacy of steroid-soaked, absorbable calcium alginate nasal packing following endoscopic sinus surgery. STUDY DESIGN: Prospective, randomized, single-blinded, placebo-controlled trial. METHODS: Twenty-two patients (44 nostrils) who had chronic rhinosinusitis with polyps underwent bilateral endoscopic sinus surgery. Only those with an intersinus difference in Lund-Mackay severity score of 1 or less were included. In each patient, one randomly selected nostril was packed with calcium alginate soaked with 2 mL of triamcinolone (40 mg/mL) (triamcinolone group), whereas the contralateral nostril received an identical packing soaked in 2 mL of normal saline (saline group). Two independent investigators blinded to the packing allocation scored the surgical field using the validated Perioperative Sinus Endoscopy (POSE) scores 1, 4, and 8 weeks after surgery. RESULTS: All 44 nostrils were analyzed; the Lund-Mackay scores did not differ significantly between the groups before surgery. Eight weeks after surgery, the total POSE scores were significantly lower in the triamcinolone group (P = .014). The POSE scoring parameters were then compared between groups, and the following variables were significantly different: middle turbinate synechiae with the lateral wall (P = .037), polypoid degeneration of the ethmoid cavity (P = .006), and sphenoid sinus severity (P = .036). CONCLUSIONS: This study demonstrated that steroid-soaked, absorbable nasal packing can be used to enhance wound healing after endoscopic sinus surgery and to prevent polypoid changes in the nasal mucosa. LEVEL OF EVIDENCE: 1b. Laryngoscope, 128:311-316, 2018.

Reactogenicity and safety assessment of an attenuated nanovaccine against scorpion envenomation: Preclinical study.

An attenuated nanovaccine (Nps - V∗) has been developed to protect humans from fatal scorpion envenomation in at-risk regions. This study was conducted to evaluate the toxicity and the local reactogenicity of the Nps - V∗ nanovaccine developed against Androctonus australis hector (Aah) venom. Assessment of the systemic inflammatory response and serum cytokine levels were evaluated in vaccinated mice with 100µg of irradiated Aah venom (V∗) encapsulated or not into polymeric calcium-alginate nanoparticles (Nps) and injected by subcutaneous (s.c) route. The local reactogenicity was evaluated by dermal Draize observations and skin tissue analysis at the injection site of vaccinated rabbits with 250 or 500µg of V∗-loaded into Nps. All animals gained weight and had normal food consumption during the study. Additionally, results showed that the nanoformulation Nps - V∗ did not cause clinical evidence of systemic toxicity in mice or rabbits, a transient edema/erythema at the injection site was only recorded as treatment-related reactogenicity. These results indicated a favorable safety profile for Nps - V∗ and supported its use in superior animal tests, then in a Phase 1 clinical trial.

Drug-Loadable Calcium Alginate Hydrogel System for Use in Oral Bone Tissue Repair.

This study developed a drug-loadable hydrogel system with high plasticity and favorable biological properties to enhance oral bone tissue regeneration. Hydrogels of different calcium alginate concentrations were prepared. Their swelling ratio, degradation time, and bovine serum albumin (BSA) release rate were measured. Human periodontal ligament cells (hPDLCs) and bone marrow stromal cells (BMSCs) were cultured with both calcium alginate hydrogels and polylactic acid (PLA), and then we examined the proliferation of cells. Inflammatory-related factor gene expressions of hPDLCs and osteogenesis-related gene expressions of BMSCs were observed. Materials were implanted into the subcutaneous tissue of rabbits to determine the biosecurity properties of the materials. The materials were also implanted in mandibular bone defects and then scanned using micro-CT. The calcium alginate hydrogels caused less inflammation than the PLA. The number of mineralized nodules and the expression of osteoblast-related genes were significantly higher in the hydrogel group compared with the control group. When the materials were implanted in subcutaneous tissue, materials showed favorable biocompatibility. The calcium alginate hydrogels had superior osteoinductive bone ability to the PLA. The drug-loadable calcium alginate hydrogel system is a potential bone defect reparation material for clinical dental application.

Immunological Challenges Facing Translation of Alginate Encapsulated Porcine Islet Xenotransplantation to Human Clinical Trials.

Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves. The lack of standardization of significant parameters of bioencapsulation device design and manufacture (i.e., purification protocols, surface-modification grafting techniques, alginate composition modifications) between labs is yet another obstacle that must be overcome before a clinically effective and applicable protocol for encapsulating islets can be implemented. Nonetheless, substantial progress is being made, as is evident from prolonged graft survival times and improved protection from immune-mediated graft destruction reported by various research groups, but also with regard to discoveries of specific pathways involved in explaining observed outcomes. Progress in the latter is essential for a comprehensive understanding of the mechanisms responsible for the varying levels of immunogenicity of certain alginate devices. Successful translation of encapsulated islet transplantation from in vitro and animal model testing to human clinical trials hinges on application of this knowledge of the pathways and interactions which comprise immune-mediated rejection. Thus, this review not only focuses on the different factors contributing to provocation of the immune reaction by encapsulated islets, but also on the defining characteristics of the response itself.

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors.

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-ß3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors.

Nanoparticles based on oleate alginate ester as curcumin delivery system.

Hydrophobic alginate derivative was prepared by the modification of alginate with methyl oleate. The synthesized oleate alginate ester (OAE) conjugate was characterized by FTIR and (1)HNMR analysis. Results of critical aggregation concentration (CAC) revealed that OAE conjugate had low CAC and was prone to form self-assembled nanoparticles in aqueous medium. Curcumin loaded OAE nanoparticles (Cur-OAE Nps) were developed by a simple sonication method and the physicochemical parameters of the nanoparticles such as zeta potential, size distribution and drug encapsulation were characterized. The results showed that zeta potential of the prepared nanoparticles was -55.4±0.91 mV and the average size was about 200 nm. A significant enhancement in aqueous solubility and stability of curcumin were observed after encapsulation into OAE nanoparticles. With the increase of curcumin concentration, loading efficiency increased but encapsulation efficiency decreased. The in vitro release profile exhibited significant sustained release pattern with initial burst release followed by a slower release over a period of one week. Cytotoxicity assay against MCF-7cells showed that Cur-OAE Nps had slow and continuous cytotoxic effect. Furthermore, in vitro cell uptake study revealed that cell uptake of curcumin from OAE nanoparticles was sustained and both were time and concentration dependent. Therefore, the developed Cur-OAE Nps might be promising candidates for curcumin delivery to cancer cells.

Development and characterization of alginate coated low molecular weight chitosan nanoparticles as new carriers for oral vaccine delivery in mice.

In the present study, nanoparticles of low MW chitosan (CS) were formulated in which measles antigen was entrapped and subsequently coated with sodium alginate. The size and surface properties of the nanoparticle can be tuned with different MW of CS. In vitro release studies showed initial burst release followed by extended release, best fitted in the Makoid-Banakar model (R(2)>0.98). SDS-PAGE assay revealed that alginate coating could effectively protect antigen in acidic condition for at least 2h. Cell viability was assessed using MTT assay into HT 29 cell line. Formulations were orally administered to mice and immunological responses were evaluated using ELISA method. Obtained results showed that measles antigen-loaded CS nanoparticles induced strong immune response and significant correlation was observed between the immune response with CS MW. Protecting ability of antigen in gastric environment, sustained release kinetics, systemic and mucosal immune responses and low cytotoxicity observed for the alginate coated nanoparticles demonstrated that LMW CS could be promising platform for oral vaccine delivery.

Adverse effects of fillers and their histopathology.

Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options.

Intracoronary delivery of injectable bioabsorbable scaffold (IK-5001) to treat left ventricular remodeling after ST-elevation myocardial infarction: a first-in-man study.

BACKGROUND: We aimed to test, for the first time, the feasibility of intracoronary delivery of an innovative, injectable bioabsorbable scaffold (IK-5001), to prevent or reverse adverse left ventricular remodeling and dysfunction in patients after ST-segment-elevation myocardial infarction. METHODS AND RESULTS: Patients (n=27) with moderate-to-large ST-segment-elevation myocardial infarctions, after successful revascularization, were enrolled. Two milliliters of IK-5001, a solution of 1% sodium alginate plus 0.3% calcium gluconate, was administered by selective injection through the infarct-related coronary artery within 7 days after myocardial infarction. IK-5001 is assumed to permeate the infarcted tissue, cross-linking into a hydrogel and forming a bioabsorbable cardiac scaffold. Coronary angiography, 3 minutes after injection, confirmed that the injection did not impair coronary flow and myocardial perfusion. Furthermore, IK-5001 deployment was not associated with additional myocardial injury or re-elevation of cardiac biomarkers. Clinical assessments, echocardiographic studies, 12-lead electrocardiograms, 24-hour Holter monitoring, blood tests, and completion of Minnesota Living with Heart Failure Questionnaires were repeated during follow-up visits at 30, 90, and 180 days after treatment. During a 6-month follow-up, these tests confirmed favorable tolerability of the procedure, without device-related adverse events, serious arrhythmias, blood test abnormalities, or death. Serial echocardiographic studies showed preservation of left ventricular indices and left ventricular ejection fraction. CONCLUSIONS: This first-in-man pilot study shows that intracoronary deployment of an IK-5001 scaffold is feasible and well tolerated. Our results have promoted the initiation of a multicenter, randomized controlled trial to confirm the safety and efficacy of this new approach in high-risk patients after ST-segment-elevation myocardial infarction. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01226563.

Alginate gelation-induced cell death during laser-assisted cell printing.

Modified laser-induced forward transfer has emerged as a promising bioprinting technique. Depending on the operating conditions and cell properties, laser cell printing may cause cell injury and even death, which should be carefully elucidated for it to be a viable technology. This study has investigated the effects of alginate gelation, gelation time, alginate concentration, and laser fluence on the post-transfer cell viability of NIH 3T3 fibroblasts. Sodium alginate and calcium chloride are used as the gel precursor and gel reactant solution to form cell-laden alginate microspheres. It is found that the effects of gelation depend on the duration of gelation. Two-minute gelation is observed to increase the cell viability after 24 h incubation, mainly due to the protective cushion effect of the forming gel membrane during droplet landing. Despite the cushion effect from 10 min gelation, it is observed that the cell viability decreases after 24 h incubation because of the forming thick gel membrane that reduces nutrient and oxygen diffusion from the culture medium. In addition, the cell viability after 24 h incubation decreases as the laser fluence or alginate concentration increases.

Microencapsulation of lectin anti-cancer agent and controlled release by alginate beads, biosafety approach.

Hepatocellular carcinoma (HCC) is considered as one of the most aggressive cancer worldwide. In Egypt, the prevalence of HCC is increasing during last years. Recently, drug-loaded microparticles were used to improve the efficiency of various medical treatments. This study is designed to evaluate the anticancer potentialities of lectins against HCC while hinting to its safety usage. The aim is also extended to encapsulate lectins in alginate microbeads for oral drug delivery purposes. The extracted lectins showed anti-proliferative effect against HCC with a percentage of 60.76% by using its nontoxic dose with an up-regulation of P53 gene expression. Concerning the handling of lectin alginate microbeads for oral drug delivery, the prepared lectin alginate beads were ∼100µm in diameter. The efficiency of the microcapsules was checked by scanning electron microscopy, the SEM showed the change on the alginate beads surface revealing the successful lectin encapsulation. The release of lectins from the microbeads depended on a variety of factors as the microbeads forming carriers and the amount-encapsulated lectins. The Pisum sativum extracted lectins may be considered as a promising agent in controlling HCC and this solid dosage form could be suitable for oral administration complemented with/or without the standard HCC drugs.

Control of multi-drug-resistant pathogens with non-thermal-plasma-treated alginate wound dressing.

BACKGROUND: Non-thermal dielectric-barrier discharge plasma (non-thermal plasma) is being investigated for use in wound healing. Alginate gel, already in clinical use, is non-toxic but has no meaningful antimicrobial property. This study reports that a non-thermal-plasma-treated alginate wound dressing has strong antimicrobial properties. METHODS: Alginate gel was treated with non-thermal plasma in room air and inoculated with bacterial pathogens. At 15 min after this, bacterial cell viability was determined by colony assay or 2,3-bis-(2-methoxy-4- nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The anti-biofilm efficacy of the non-thermal-plasma-treated alginate gel was investigated and the treated gel was tested against vascular endothelial cells for a cytotoxic effect. The proliferation and migration of bacterial cells before and after exposure to the treated gel were investigated with an in vitro wound testing assay. Scanning electron microscopy was used to observe changes in the gel surface associated with exposure to bacterial pathogens. The treated gel was tested against Acinetobacter baumannii, Escherichia coli, Staphylococcus aureus, S. epidermidis, Candida albicans, and C. glabrata as representative pathogens (at 10(6)-10(9) colony-forming units [CFU]/mL), and the thickness of a plasma-treated gel dressing and distance between a glass dielectric-barrier discharge plasma probe and the gel surface were kept constant. RESULTS: Non-thermal-plasma-treated alginate gel exhibited a strong biocidal property and inactivated all of the pathogens included in the study at counts of 10(8) CFU/mL and within 15 sec of treatment. The treated gel inactivated 10(9) CFU/mL of the organisms within 1 min, and 3 min of exposure to the treated gel inactivated pathogens embedded in biofilms. The plasma-treated gel showed no significant cytotoxicity, and endothelial cells exposed to the treated gel proliferated and migrated well across a wound area over a period of time. Dressings made with the treated gel retained their biocidal effects for about a month. Scanning electron microscopy showed no damage to the surfaces of treated gels, but damage to the bacterial pathogens on plasma exposure. CONCLUSION: A non-thermal-plasma-treated alginate gel dressing has the clinical potential to decontaminate wounds, prevent surgical site infection, and promote wound healing.

[Comparative study of osteoplastic materials based on chitosan, alginate or fibrin with tricalcium phosphate].

The study presents comparative analysis of porous composites made of chitosan, alginate, fibrin with beta-tricalcium phosphate. Histological findings on Wistar rat condyles showed that fibrin-beta-TCP-based composite had the most effective positive biological response.

Vacuum-assisted wound closure versus alginate for the treatment of deep perivascular wound infections in the groin after vascular surgery.

BACKGROUND: Vacuum-assisted wound closure (VAC) therapy may heal wounds faster than conventional dressings after surgical debridement of perivascular groin infections after vascular surgery. METHODS: Patients with deep infected wounds (Szilagyi grade III) were surgically revised and left open for secondary healing, then randomized to either VAC or alginate (Sorbalgon) therapy, between February 2007 and November 2011. To test the hypothesis, it was calculated that 42 patients needed to be included (90% power, 5% level of significance). It was decided to perform an interim analysis after inclusion of 20 patients. RESULTS: Among 66 patients undergoing groin revision, 20 patients were included in this study. Patients were randomized to VAC (n = 10) or alginate (n = 10). The two groups were comparable in patient and wound characteristics. Time to full skin epithelialization was significantly shorter in the VAC group (median, 57 days) compared with the alginate group (median, 104 days; P = .026). The number of positive wound cultures of bacteria and C-reactive protein values decreased equally in both groups between surgical revision and day 21. One femur amputation was performed in each group as a consequence of the groin infection, one patient died during the in-hospital stay in the alginate group, and none died in the VAC group. CONCLUSIONS: VAC achieves faster healing than alginate therapy after wound debridement for deep perivascular wound infections in the groin after vascular surgery. This finding does not allow further inclusion of patients from an ethical point of view, and this study was, therefore, stopped prematurely.

Gastroesophageal reflux in pregnancy: a systematic review on the benefit of raft forming agents.

The prevalence of gastroesophageal reflux disease (GERD) symptoms in pregnancy is very high, up to 80%, with a maximum peak during the third trimester. Together with lifestyle modifications, antacids and antisecretive agents, such as proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2RAs), are commonly prescribed in non-pregnant, adult population. In certain Countries these drugs are not allowed in or are allowed only during the late stages of pregnancy. Alginate-based formulations have been used for the symptomatic treatment of heartburn for decades, as they usually contain sodium or potassium bicarbonate. In the presence of gastric acid, a foamy raft is created above the gastric contents. The alginate raft moves into the esophagus in place or ahead of acidic gastric contents during reflux episodes physically preventing reflux of gastric contents into the esophagus. Alginate-based formulations are allowed with no restrictions also in pregnancy: their safety profile make them a very valid option taking into account the risk/benefit ratio for both parturient and unborn baby. This systematic review paper aims to explore the use of medications for treating GERD in pregnancy, including alginate raft-forming-agents, highlighting the benefits for both the mother and the fetus. Electronic search in databases was conducted on databases such as Medline, PubMed, Ovid retrieving data concerning the reflux treatments in pregnancy, with a special focus on alginate raft forming antireflux agents. From the literature on alginate use in pregnancy, no particular risks have been shown to date for both parturient and unborn baby when alginate had been administered during all the pregnancy trimesters. The physical mode of action ensures the maximum esophageal protection by the neutral foam floating in the stomach, maintaining physiological pH values at stomach level, without interfering with the digestive processes. The symptoms' healing has been markedly improved during the weeks of observation; the symptoms monitored in all studies were: heartburn, regurgitation, pain (chest). After four weeks of treatment little or no change was observed in maternal mean sodium or potassium concentrations. No sodium restriction diet has been adopted. No edema of lower limbs or weight gain occurred. No adverse reactions related to the testing drug had been reported and all the authors concluded that alginate was safe for the unborn baby. Nowadays pharmacological treatments for GER are available as OTC drugs, including antacids, antisecretive agents, PPIs and H2RAs, and as medical devices, such as alginate raft forming antireflux agents (i.e.: Reflubloc™, Novartis NCH Italy). On this last product, considering the specific indication in pregnancy and the safety profile, without restrictions of administration during the whole pregnancy period, furthermore the physical mode of action, it gives the gynecologists a very important option in treating GER in pregnancy, taking care of both pregnant and fetus. Raft-forming-antireflux agents are safe and effective in GER treatment during pregnancy.