Dosing metric in cellular experiments: The mol/cell metric has its limitations.

It has been argued that the mol/cell metric is more universal than concentration of the toxic agent since in many cases the effect of dose expressed as mol/cell is independent of ex-perimental setup. We confirmed it for hemolysis of erythrocytes in phosphate-buffered saline induced by hypochlorite where the amount of femtomoles/cell of hypochlorite needed for 50% hemolysis was independent of erythrocyte concentration. However, in the presence of blood plasma this metric became dependent on cell concentration. Similarly, the effect of 3-bromopyruvic acid (3-BP) on PEO1 cells as a function of mol/cell ratio depended on the volume of the 3-BP containing medium, due to the reaction of 3-BP with components of the medium. Hemolytic amounts of sodium dodecyl sulfate and Triton X-100 expressed as mol/cell decreased with increasing cell concentration while the effect of DMSO on the viability of a constant number of fibroblasts was independent of the volume of DMSO-containing medium. These results demonstrate that the mol/cell metric is still dependent on experimental conditions when the toxic agent interacts with components of the medium or when its physical state is modified by the target cells, and the effect is independent of the mol/per cell ratio for high excess of a cell damaging agent.

Effect of hypochlorous acid nasal spray as an adjuvant therapy after functional endoscopic sinus surgery.

OBJECTIVES: To evaluate the efficacy of hypochlorous acid (HOCl) nasal spray as an adjuvant therapy after functional endoscopic sinus surgery (FESS). MATERIAL AND METHODS: Patients with chronic rhinosinusitis who had received FESS for treatment were recruited and assigned to one of two groups at random at one month post-surgery. In the HOCl group, patients received 0.02% HOCl nasal spray three times a day for two months. In the control group, normal saline (NS) nasal irrigation was given. Before FESS and before and after nasal spray or irrigation, patients completed the Taiwanese version of the 22-item Sino-Nasal Outcome Test (TWSNOT-22). In addition, patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial cultures obtained from their middle meatus. RESULTS: Seventy-eight patients completed the study. Among them, 41 received HOCl nasal spray, and 37 received NS irrigation. Endoscopic score significantly decreased after 2-month HOCl nasal spray (p = 0.036). TWSNOT-22 score also decreased, although insignificantly (p = 0.285). In contrast, TWSNOT-22 score significantly decreased after NS nasal irrigation (p = 0.017), but endoscopic score did not significantly decrease (p = 0.142). CONCLUSIONS: Our results showed that HOCl nasal spray had a similar effect to that of NS nasal irrigation in post-FESS care. It can be an alternative of NS nasal irrigation for its convenient application.

Mesenchymal stromal cells-derived extracellular vesicles alleviate systemic sclerosis via miR-29a-3p.

Systemic sclerosis (SSc) is a potentially lethal disease with no curative treatment. Mesenchymal stromal cells (MSCs) have proved efficacy in SSc but no data is available on MSC-derived extracellular vesicles (EVs) in this multi-organ fibrosis disease. Small size (ssEVs) and large size EVs (lsEVs) were isolated from murine MSCs or human adipose tissue-derived MSCs (ASCs). Control antagomiR (Ct) or antagomiR-29a-3p (A29a) were transfected in MSCs and ASCs before EV production. EVs were injected in the HOCl-induced SSc model at day 21 and euthanasized at day 42. We found that both ssEVs and lsEVs were effective to slow-down the course of the disease. All disease parameters improved in skin and lungs. Interestingly, down-regulating miR-29a-3p in MSCs totally abolished therapeutic efficacy. Besides, we demonstrated a similar efficacy of human ASC-EVs and importantly, EVs from A29a-transfected ASCs failed to improve skin fibrosis. We identified Dnmt3a, Pdgfrbb, Bcl2, Bcl-xl as target genes of miR-29a-3p whose regulation was associated with skin fibrosis improvement. Our study highlights the therapeutic role of miR-29a-3p in SSc and the importance of regulating methylation and apoptosis.

A Concept for the Reduction of Mucosal SARS-CoV-2 Load using Hypochloric Acid Solutions.

During the next few months or years, vaccination against SARS-CoV-2 infection will significantly reduce the morbidity and mortality of COVID-19. However, additional measures are needed to protect those who are still not immunized. This is even more important in view of new viral mutations that result in increased transmission rates. We propose that the use of long-standing medicinal solutions based on hypochloric acid (HOCl) and intended for application on wounds may be effective as a gargling solution or nasal irrigation in blocking transmission of the virus. Here, we propose the use of HOCl-containing solutions for blocking the transmission of SARS-CoV-2 in combination with other prevention measures. This may constitute another important cornerstone in the fight against the COVID-19 pandemic.

Combined anti-fibrotic and anti-inflammatory properties of JAK-inhibitors on macrophages in vitro and in vivo: Perspectives for scleroderma-associated interstitial lung disease.

Janus kinase (JAK) inhibitors (also termed Jakinibs) constitute a family of small drugs that target various isoforms of JAKs (JAK1, JAK2, JAK3 and/or tyrosine kinase 2 (Tyk2)). They exert anti-inflammatory properties linked, in part, to the modulation of the activation state of pro-inflammatory M1 macrophages. The exact impact of JAK inhibitors on a wider spectrum of activation states of macrophages is however still to be determined, especially in the context of disorders involving concomitant activation of pro-inflammatory M1 macrophages and profibrotic M2 macrophages. This is especially the case in autoimmune pulmonary fibrosis like scleroderma-associated interstitial lung disease (ILD), in which M1 and M2 macrophages play a key pathogenic role. In this study, we directly compared the anti-inflammatory and anti-fibrotic effects of three JAK inhibitors (ruxolitinib (JAK2/1 inhibitor); tofacitinib (JAK3/2 inhibitor) and itacitinib (JAK1 inhibitor)) on five different activation states of primary human monocyte-derived macrophages (MDM). These three JAK inhibitors exert anti-inflammatory properties towards macrophages, as demonstrated by the down-expression of key polarization markers (CD86, MHCII, TLR4) and the limited secretion of key pro-inflammatory cytokines (CXCL10, IL-6 and TNFα) in M1 macrophages activated by IFNγ and LPS or by IFNγ alone. We also highlighted that these JAK inhibitors can limit M2a activation of macrophages induced by IL-4 and IL-13, as notably demonstrated by the down-regulation of the M2a associated surface marker CD206 and of the secretion of CCL18. Moreover, these JAK inhibitors reduced the expression of markers such as CXCL13, MARCO and SOCS3 in alternatively activated macrophages induced by IL-10 and dexamethasone (M2c + dex) or IL-10 alone (M2c MDM). For all polarization states, Jakinibs with inhibitory properties over JAK2 had the highest effects, at both 1 µM or 0.1 µM. Based on these in vitro results, we also explored the effects of JAK2/1 inhibition by ruxolitinib in vivo, on mouse macrophages in a model of HOCl-induced ILD, that mimics scleroderma-associated ILD. In this model, we showed that ruxolitinib significantly prevented the upregulation of pro-inflammatory M1 markers (TNFα, CXCL10, NOS2) and pro-fibrotic M2 markers (Arg1 and Chi3L3). These results were associated with an improvement of skin and pulmonary involvement. Overall, our results suggest that the combined anti-inflammatory and anti-fibrotic properties of JAK2/1 inhibitors could be relevant to target lung macrophages in autoimmune and inflammatory pulmonary disorders that have no efficient disease modifying drugs to date.

A novel reaction-based fluorescence probe for rapid imaging of HClO in live cells, animals, and injured liver tissues.

Hypochlorous acid (HClO) is an important bioactive molecule, playing vital roles in a large number of physiological and pathological processes. Abnormal concentration of HClO in vivo has close contact with many diseases including inflammatory diseases and cancer. For bioimaging HClO, a new colorimetric and turn-on near-infrared (NIR) fluorescence probe (DDAO-ClO) was designed and synthesized in this work through a specific reaction of HClO with dimethylthiocarbamate. DDAO-ClO proved to show distinct and highly selective colorimetric and NIR fluorescence responses for HClO with fast response time (<3 s) and high sensitivity (LOD = 7.3 nM) in vitro. After confirming the excellent in vitro sensing ability, imaging HClO with DDAO-ClO in living HeLa cells, MCF-7 cells, zebrafish, and mice was all successfully demonstrated. And with this probe, it was further discovered that more endogenous HClO was produced in injured mice liver tissues, which demonstrates that DDAO-ClO not only is effective for in vivo detection of HClO but also has a broad application prospect.

Túneles de desinfección peatonal pulverizadores de ozono y otros desinfectantes para disminuir la propagación del SARS-CoV-2 / Pedestrian disinfection tunnels, ozone sprays and other disinfectants to reduce the spread of SARS-CoV-2

INTRODUCCIÓN: Queda mucho por aprender sobre el nuevo coronavirus (SARS-CoV-2) que causa la enfermedad por coronavirus 2019 (COVID-19). Según lo que se sabe actualmente sobre el virus y sobre coronavirus similares que causan SARS y MERS, la propagación de persona a persona ocurre con mayor frecuencia entre contactos cercanos (dentro de aproximadamente 2 metros) a través de gotitas respiratorias generadas por una persona infectada al toser o estornudar (CDC 2020). La transmisión también puede ocurrir de forma indirecta por contacto con superficies que se encuentran en el entorno inmediato de una persona infectada o con objetos que esta haya utilizado (OMS 2020b). La transmisión del coronavirus en general ocurre mucho más comúnmente a través de gotitas respiratorias que a través de fómites (CDC 2020). Por otro lado, se ha reportado que el SARS-CoV-2 puede permanecer viable durante horas o días en superficies hechas de una variedad de materiales. En ese sentido, la desinfección de superficies es considerada una buena práctica para la prevención de COVID-19 y otras enfermedades respiratorias virales en entornos comunitarios (CDC 2020). Sin embargo, en países como China, México y Argentina se han visto imágenes en donde los desinfectantes son rociados directamente a las personas cuando estas pasan a través de túneles instalados en lugares públicos de alto tránsito, como entradas a mercados, edificios administrativos u hospitales. Esta medida ha sido cuestionada ya que el desinfectante usado en estos túneles puede causar irritación en las personas, así como daño en la piel y los ojos (Neustaeter 2020). El túnel de desinfección peatonal consiste en un sistema de aspersores que rocían al peatón un desinfectante con el fin de desinfectar la ropa. Cada persona debe permanecer en el interior del túnel unos pocos segundos con las manos en alto para permitir que la mezcla sanitizante llegue a la mayoría de las partes del cuerpo (Infobae 2020). Dentro de los desinfectantes utilizados se encuentran el amonio cuaternario, el ozono, el ácido hipocloroso, el alcohol, soluciones de hipoclorito, catalizadores orgánicos, entre otros (Minsalud 2020). El uso de esta innovación tecnológica ha sido propuesto por algunas personas como una medida sanitaria adicional a las ya establecidas (distanciamiento físico, uso de mascarillas, lavado de mano) para reducir el contagio del SARS-CoV-2 en lugares públicos de alta concurrencia. Actualmente, esta propuesta se ha difundido de manera mediática captando el interés de diversas instituciones para su posible incorporación. Al respecto, la Dirección General de Salud Ambiental del Perú (DIGESA), con fecha 16 de abril de 2020, realizó un pronunciamiento desalentando el uso de túneles desinfectantes para evitar la transmisión de COVID-19. En esta nota se enfatiza que no existe evidencia científica de que los túneles desinfectantes sean efectivos para impedir la transmisión del virus, y que por el contrario, los desinfectantes dispersados sobre los peatones podrían ser dañinos para la salud e incluso aumentar el riesgo de dispersión del SARS-CoV-2. También se señala que toda desinfección para evitar la transmisión de COVID-19 se debe realizar sobre superficies inertes como mesas, pisos o estantes, y no sobre personas (DIGESA 2020). A pesar del pronunciamiento por parte de la DIGESA, el IETSI ha recibido solicitudes de evaluación, en donde se plantea el uso de túneles de desinfección generales y, específicamente, los de ozono. Así, surge la necesidad de conocer el funcionamiento de los túneles de desinfección peatonal pulverizadores de ozono y de otros desinfectantes, así como revisar la literatura pertinente a esta tecnología para evaluar su efectividad y seguridad para disminuir la propagación del SARS-CoV-2. MÉTODOS: Primero, se realizó una búsqueda manual de guías, reportes técnicos o recomendaciones para la desinfección en el contexto del COVID-19, en las páginas web de diversas sociedades y gobiernos alrededor del mundo, tales como World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), European Centre for Disease Prevention and Control (ECDC), el Gobierno de Canadá, el Gobierno de Reino Unido, el Gobierno de Australia, el Gobierno de España, el Gobierno de Colombia, entre otros. Segundo, se realizó una búsqueda sistemática de guías o revisiones que brindaran recomendaciones con relación a la tecnología de interés utilizando la base de datos MEDLINE vía PubMed. La estrategia de búsqueda fue la siguiente: (sanitation[tiab] OR disinfect*[tiab]) AND (COVID-19 OR SARS-CoV-2 OR Coronavirus OR SARS) (144 ítems). Tercero, se realizó una búsqueda sistemática de estudios que evaluaran la efectividad y seguridad de los túneles de desinfección peatonal de ozono utilizando la base de datos MEDLINE vía PubMed, utilizando la siguiente estrategia de búsqueda: ozone AND (COVID-19 OR SARS-CoV-2 OR Coronavirus OR SARS) (10 ítems). Finalmente, se buscaron estudios adicionales que pudiesen haber escapado a las búsquedas con una estrategia de bola de nieve mediante la revisión de las listas de referencias de las publicaciones que sean de relevancia. RESULTADOS: Se identificó una guía técnica elaborada por el Ministerio de Salud y Protección de Colombia que evaluó el uso de sistemas de aspersión de productos desinfectantes sobre personas para la prevención de la trasmisión de COVID-19. También se identificó recomendaciones relacionadas al tema en las páginas web de la OMS y la EPA. CONCLUSIONES: No se recomienda el uso de túneles de desinfección peatonal pulverizadores de ozono u de otros desinfectantes ya que no se cuenta con evidencia científica sobre su efectividad para disminuir la propagación del COVID-19. Además, el uso de estos sistemas podría causar potenciales daños en la salud de las personas, como irritación de los ojos y de las vías respiratorias. De acuerdo a la información publicada por agencias regulatorias internacionales como la EPA, aún si el ozono se utilizara en concentraciones que no excedieran los estándares de salud pública, estos no eliminarían eficazmente los virus. Para el caso de túneles que utilizan otros agentes desinfectantes como soluciones de hipoclorito de sodio o alcohol, algunas instituciones ya han emitido pronunciamientos en contra del uso de estas tecnologías debido a la falta de evidencia que sustente su uso y al elevado riesgo de daño al peatón. Otros expertos señalan que el uso de túneles de desinfección podría tener un efecto opuesto al esperado, ya que la falsa sensación de seguridad por parte de los peatones podría hacer que estos disminuyan las medidas eficaces para disminuir el contagio del COVID19 como el distanciamiento social y el lavado de manos. Finalmente, a nivel mundial, el ozono y demás desinfectantes no están autorizados por ninguna autoridad de salud para su aplicación directa sobre humanos.

Topical stabilized hypochlorous acid: The future gold standard for wound care and scar management in dermatologic and plastic surgery procedures.

BACKGROUND: Hypochlorous acid (HOCl), a naturally occurring molecule produced by the immune system, is highly active against bacterial, viral, and fungal microorganisms. Moreover, HOCl is active against biofilm and increases oxygenation of the wound site to improve healing. Natural HOCl is unstable; through technology, it can be stabilized into an effective topical antiseptic agent. AIM: This paper focuses on the use of topical stabilized HOCl in wound and scar management for pre-, peri-, and postprocedures-including its ability to reduce the occurrence hypertrophic scars and keloids. The role of the product in other skin conditions is beyond the scope of this article. METHODS: A panel comprising clinicians with experience in cosmetic and surgical procedures met late 2018 to discuss literature search results and their own current clinical experience regarding topical stabilized HOCl. The panel of key opinion leaders in dermatology and plastic surgery defined key insights and consensus statements on the direction of use for the product. RESULTS: Topical stabilized HOCl provides an optimal wound healing environment and, when combined with silicone, may be ideal for reducing scarring. Additionally, in contrast to chlorhexidine, HOCl, used as an antiseptic skin preparation, raises no concerns of ocular- or ototoxicity. CONCLUSIONS: For wound care and scar management, topical stabilized HOCl conveys powerful microbicidal and antibiofilm properties, in addition to potency as a topical wound healing agent. It may offer physicians an alternative to other less desirable wound care measures.

Decontamination of aerosolised bacteria from a pig farm environment using a pH neutral electrochemically activated solution (Ecas4 anolyte).

An electrochemically activated solution (ECAS), generated by electrolysis of a dilute sodium chloride solution in a four-chamber electrolytic cell (Ecas4), was tested as a sanitising aerosol in eliminating bacteria from the environment of a weaning room vacated 24-48h earlier, at a continuous flow pig farm. An ultrasonic humidifier was used to fill the environment with a fog (droplets with diameters of 1-5 µm) containing 0.25 ppm of hypochlorous acid. The weaning room was fogged for 3 min at 30 min intervals during five hours of aerosol disinfection. An innovative sample treatment with propidium monoazide dye in conjunction with cyclonic air sampling was optimised and adapted for discerning live/dead bacteria in subsequent molecular quantification steps. Without fogging, total bacterial load ranged from 5.06 ± 0.04 to 5.75 ± 0.04 Log10 CFU/m3. After the first hour of fogging, a 78% total bacterial reduction was observed, which further increased to > 97% after the second hour, > 99.4% after the third and 99.8% after the fourth hour, finally resulting in a 99.99% reduction from the farm environment over five hours. Unlike the current formaldehyde spray disinfection protocol, which requires a long empty period because of its hazardous properties, this economically viable and environmentally friendly disinfection protocol may significantly lower downtime. Moreover, ECAS fogging can be easily adapted to a variety of applications, including the elimination of pathogens from livestock farm air environment for disease prevention, as well as decontamination after disease outbreaks.

Surgical Breast Pocket Irrigation With Hypochlorous Acid (HOCl): An In Vivo Evaluation of Pocket Protein Content and Potential HOCl Antimicrobial Capacity.

Background: Hypochlorous acid (HOCl) demonstrates rapid and broad antimicrobial activity against planktonic and biofilm phenotype bacteria in vitro. Objectives: To identify the protein content present in breast pockets in vivo and calculate the estimated active concentration of HOCl, (PhaseOne, Integrated Healing Technologies, Franklin, TN) following HOCl-protein interactions. Methods: Fluid samples were collected prior to implant insertion in 18 consecutive patients, representing 36 pocket samples, with all cases being bilateral primary breast augmentations. Samples were evaluated by an independent CLIA approved laboratory for albumin and total protein concentration in g/dL. Results were compared to HOCl solution concentration and protein binding potential to determine availability of free HOCl. Results: The mean tissue sample concentration (right and left breast) was 31.6 mg/dL which translates to 0.0001 mmol per 20 cc of interstitial fluid. Mean total protein levels (right and left breast) were 62.3 mg/dL or 0.000187 mmol per 20 cc interstitial fluid. Based upon potential stoichiometric neutralization of HOCl by proteins in either a 1:1 or 3:1 ratio, using 115 cc of HOCl solution (per breast) at a concentration of 250 ppm/mL or 0.025% HOCl or = 0.48 mmol HOCl/dL, there would be 2950 times the amount of active HOCl at a 1:1 reaction ratio, or 983 times more HOCl assuming a 3:1 reaction ratio. Based on the range of identified levels of protein in individual surgical pockets in the study, there is an estimated 242 to 12,500 times more HOCl molecules than protein at a 3:1 molar ratio of binding or reactive protein. Conclusions: n estimated range of 983-2950 times more HOCl molecules are present during irrigation with 230 cc of PhaseOne® (115 cc for each breast) than available protein. This supports the antimicrobial and anti-biofilm activity as described in previous in vitro studies when using PhaseOne® as part of pocket irrigation.

Topical Hypochlorite and Skin Acidification Improves Erythroderma of Omenn Syndrome.

We describe a case of Omenn syndrome displaying exudative erythroderma and other characteristic features, including alopecia, absent B and naïve T cells, hyper immunoglobulin E levels, and eosinophilia. A pathogenic recombination-activating RAG1 homozygous genetic mutation confirmed the diagnosis. She required frequent antibiotics at both treatment and prophylactic doses, which alone did not control her erythroderma, but her high risk of infection precluded the use of systemic agents such as cyclosporine, which would further suppress her already severely compromised immune system. Thrice-weekly topical dilute hypochlorite compresses, combined with skin acidification with a low pH emollient, were initiated to control inflammation and for cutaneous bacterial prophylaxis. She demonstrated a marked improvement in her erythroderma within days after treatment initiation. Further improvement continued with the addition of systemic corticosteroids, with resolution of erythroderma after her first dose. This case reveals for the first time that dilute topical hypochlorite and skin pH restoration holds promise to control severe dermatitis associated with immunodeficiency and inflammatory syndromes with minimal side effects.

Evaluation of substantivity of hypochlorous acid as an antiplaque agent: A randomized controlled trial.

BACKGROUND: Hypochlorous acid (HOCl) is a non-antibiotic antimicrobial substance with significant effects on pathogenic oral micro-organisms. The effects of HOCl as an antiplaque agent have not been studied. OBJECTIVE: The aim of this study was to evaluate the substantivity of HOCl mouthwashes compared with chlorhexidine (CHX) rinses and a placebo. MATERIALS AND METHODS: A double-blind randomized controlled trial with 75 participants was conducted. Participants were divided into five groups using block randomization: 0.025% HOCl, 0.05% HOCl, 0.12% CHX, 0.2% CHX, and sterile water as a placebo. Participants were instructed to use each rinse solution for 30 seconds after dental prophylaxis. Samples of saliva were taken at baseline and after 30 seconds, 1, 3, 5 and 7 hours to assess substantivity, and bacterial viability was established by the fluorescence method. Visible plaque in all participants was assessed with the Turesky index at baseline and at 7 hours, and adverse events were also assessed. RESULTS: HOCl led to a 33% reduction in bacterial counts in the saliva after 30 seconds compared with a 58% reduction by CHX. HOCl has no substantivity, and bacterial counts returned to baseline after 1 hour. Placebo treatment led to the highest plaque count after 7 hours compared with the CHX and HOCl groups, although the differences were not significant. HOCl rinsing induced the highest percentages of unpleasant taste and dryness sensations. CONCLUSIONS: HOCl rinses have an initial effect on bacterial viability in saliva but have no substantivity. Other mechanisms may explain its antiplaque effect.

Preliminary Results of the Use of a Stabilized Hypochlorous Acid Solution in the Management of Ralstonia Pickettii Biofilm on Silicone Breast Implants.

BACKGROUND: Ralstonia Pickettii biofilms are associated with pocket infections following breast implant surgeries. Biofilm protects bacteria most topically applied antimicrobial irrigations. OBJECTIVES: To evaluate the effectiveness of four antimicrobial solutions on the planktonic form and established biofilm of Ralstonia Pickettii grown on 3 different types of silicone breast implants. METHODS: Time kill assays at clinical concentrations of chlorhexidine gluconate, povidone iodine, triple-antibiotic solution, and a 0.025% hypochlorous acid solution stabilized in amber glass were evaluated. Normal saline was the control. Three types of silicone implants, two with a textured surface and one smooth surface, were selected. Planktonic assays were performed after implants were soaked for one, five, 30, and 120 minute time points. Biofilm assays were performed after 5 and 120 minutes of implant soak time. Both tests evaluated cell-forming units (CFU/mL). RESULTS: Triple antibiotic solution had no effect on R. pickettii and was dropped from the study. Remaining solutions showed total kill of planktonic bacteria at one minute. Saline control showed no significant effect on biofilm as anticipated. Stabilized hypochlorous acid was the only solution tested capable of eradicating R. pickettii biofilm on all implant surfaces tested within the first five minute soak time. CONCLUSIONS: Noncytotoxic, 0.025% hypochlorous acid in normal saline, stabilized in amber glass, successfully eradicated Ralstonia pickettii in planktonic and mature biofilm on three types of silicone implants during initial five minute soak time and may be the preferred antimicrobial solution for pocket lavage. This preliminary study requires further investigation. Leaching and implant compatibility testing is currently in progress.

Hypochlorous Acid Versus Povidone-Iodine Containing Irrigants: Which Antiseptic is More Effective for Breast Implant Pocket Irrigation?

BACKGROUND: Capsular contracture induced by chronic subclinical infection is a major cause of poor outcomes and reoperation in breast implant surgery. The use of pocket irrigation with antiseptic/antibiotic has been shown to reduce the incidence of contracture. A new formulation of hypochlorous acid solution PhaseOne has been proposed as potential agent for irrigation. OBJECTIVES: This study aimed to test the efficacy of hypochlorous acid solution PhaseOne for use in breast pocket irrigation as an alternative to povidone iodine solution Betadine. METHODS: The efficacy of PhaseOne, a hypochlorous acid formulated wound and skin cleanser, was tested in vitro against planktonic and biofilm Staphylococcus aureus with or without biological soil and in an implant attachment assay. Its activity was compared with Betadine containing 10% povidone iodine. RESULTS: Our findings showed that PhaseOne was unable to eradicate planktonic and/or biofilm S. aureus in the presence of either tryptone soy broth or bovine calf serum (protein soil) in a variety of in vitro assays. CONCLUSIONS: We advise that povidone iodine containing irrigants are superior to hypochlorous acid containing irrigants in the clinical setting and should remain the recommended solution for pocket irrigation to reduce bacterial contamination at breast implants surgery.

iNOS Activity Is Required for the Therapeutic Effect of Mesenchymal Stem Cells in Experimental Systemic Sclerosis.

Objectives: Fibrosis is a hallmark of systemic sclerosis (SSc), an intractable disease where innovative strategies are still being sought. Among novel anti-fibrotic approaches, mesenchymal stromal/stem cell (MSC)-based therapy appears promising. Previously, we reported anti-fibrotic effects of MSC in an experimental model of SSc, through various mechanisms (tissue remodeling, immunomodulation, anti-oxidant defense). Since immunomodulation is a pivotal mechanism for MSC therapeutic effects, we investigated the specific role of critical molecules associated with MSC immunosuppressive properties and hypothesized that MSC defective for these molecules would be less effective in reducing fibrosis in SSc. Methods: SSc was induced by 6-week daily intradermal injections of hypochlorite (HOCl) in mice. MSC were isolated from the bone marrow of wild type mice (WT) or mice knockout for IL1RA, IL6, or iNOS (IL1RA-/-, IL6-/-, or iNOS-/- MSC, respectively). Treated-mice received 2.5 × 105 MSC intravenous infusion at d21. Skin thickness, histological and biological parameters were evaluated in skin and blood at d42. Results: IL1RA-/- and IL6-/- MSC exerted similar anti-fibrotic properties as WT MSC, with a reduction of skin thickness together with less collagen deposition. Conversely, iNOS-/- MSC did not exert anti-fibrotic functions as shown by a similar skin thickness progression as non-treated HOCl-SSc mice. Compared with WT MSC, iNOS-/- MSC kept some immunosuppressive and tissue remodeling properties, but lost their capacity to reduce oxidative stress in HOCl-SSc mice. Conclusion: Our study highlights the crucial role of iNOS, whose activity is required for the anti-fibrotic properties of MSC in experimental SSc, with a special emphasis on NO-related anti-oxidant functions.

Intracavity lavage and wound irrigation for prevention of surgical site infection.

BACKGROUND: Surgical site infections (SSIs) are wound infections that occur after an operative procedure. A preventable complication, they are costly and associated with poorer patient outcomes, increased mortality, morbidity and reoperation rates. Surgical wound irrigation is an intraoperative technique, which may reduce the rate of SSIs through removal of dead or damaged tissue, metabolic waste, and wound exudate. Irrigation can be undertaken prior to wound closure or postoperatively. Intracavity lavage is a similar technique used in operations that expose a bodily cavity; such as procedures on the abdominal cavity and during joint replacement surgery. OBJECTIVES: To assess the effects of wound irrigation and intracavity lavage on the prevention of surgical site infection (SSI). SEARCH METHODS: In February 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase and EBSCO CINAHL Plus. We also searched three clinical trials registries and references of included studies and relevant systematic reviews. There were no restrictions on language, date of publication or study setting. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of participants undergoing surgical procedures in which the use of a particular type of intraoperative washout (irrigation or lavage) was the only systematic difference between groups, and in which wounds underwent primary closure. The primary outcomes were SSI and wound dehiscence. Secondary outcomes were mortality, use of systemic antibiotics, antibiotic resistance, adverse events, re-intervention, length of hospital stay, and readmissions. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion at each stage. Two review authors also undertook data extraction, assessment of risk of bias and GRADE assessment. We calculated risk ratios or differences in means with 95% confidence intervals where possible. MAIN RESULTS: We included 59 RCTs with 14,738 participants. Studies assessed comparisons between irrigation and no irrigation, between antibacterial and non-antibacterial irrigation, between different antibiotics, different antiseptics or different non-antibacterial agents, or between different methods of irrigation delivery. No studies compared antiseptic with antibiotic irrigation. Surgical site infectionIrrigation compared with no irrigation (20 studies; 7192 participants): there is no clear difference in risk of SSI between irrigation and no irrigation (RR 0.87, 95% CI 0.68 to 1.11; I2 = 28%; 14 studies, 6106 participants). This would represent an absolute difference of 13 fewer SSIs per 1000 people treated with irrigation compared with no irrigation; the 95% CI spanned from 31 fewer to 10 more SSIs. This was low-certainty evidence downgraded for risk of bias and imprecision.Antibacterial irrigation compared with non-antibacterial irrigation (36 studies, 6163 participants): there may be a lower incidence of SSI in participants treated with antibacterial irrigation compared with non-antibacterial irrigation (RR 0.57, 95% CI 0.44 to 0.75; I2 = 53%; 30 studies, 5141 participants). This would represent an absolute difference of 60 fewer SSIs per 1000 people treated with antibacterial irrigation than with non-antibacterial (95% CI 35 fewer to 78 fewer). This was low-certainty evidence downgraded for risk of bias and suspected publication bias.Comparison of irrigation of two agents of the same class (10 studies; 2118 participants): there may be a higher incidence of SSI in participants treated with povidone iodine compared with superoxidised water (Dermacyn) (RR 2.80, 95% CI 1.05 to 7.47; low-certainty evidence from one study, 190 participants). This would represent an absolute difference of 95 more SSIs per 1000 people treated with povidone iodine than with superoxidised water (95% CI 3 more to 341 more). All other comparisons found low- or very low-certainty evidence of no clear difference between groups.Comparison of two irrigation techniques: two studies compared standard (non-pulsed) methods with pulsatile methods. There may, on average, be fewer SSIs in participants treated with pulsatile methods compared with standard methods (RR 0.34, 95% CI 0.19 to 0.62; I2 = 0%; two studies, 484 participants). This would represent an absolute difference of 109 fewer SSIs occurring per 1000 with pulsatile irrigation compared with standard (95% CI 62 fewer to 134 fewer). This was low-certainty evidence downgraded twice for risks of bias across multiple domains. Wound dehiscenceFew studies reported wound dehiscence. No comparison had evidence for a difference between intervention groups. This included comparisons between irrigation and no irrigation (one study, low-certainty evidence); antibacterial and non-antibacterial irrigation (three studies, very low-certainty evidence) and pulsatile and standard irrigation (one study, low-certainty evidence). Secondary outcomesFew studies reported outcomes such as use of systemic antibiotics and antibiotic resistance and they were poorly and incompletely reported. There was limited reporting of mortality; this may have been partially due to failure to specify zero events in participants at low risk of death. Adverse event reporting was variable and often limited to individual event types. The evidence for the impact of interventions on length of hospital stay was low or moderate certainty; where differences were seen they were too small to be clinically important. AUTHORS' CONCLUSIONS: The evidence base for intracavity lavage and wound irrigation is generally of low certainty. Therefore where we identified a possible difference in the incidence of SSI (in comparisons of antibacterial and non-antibacterial interventions, and pulsatile versus standard methods) these should be considered in the context of uncertainty, particularly given the possibility of publication bias for the comparison of antibacterial and non-antibacterial interventions. Clinicians should also consider whether the evidence is relevant to the surgical populations under consideration, the varying reporting of other prophylactic antibiotics, and concerns about antibiotic resistance.We did not identify any trials that compared an antibiotic with an antiseptic. This gap in the direct evidence base may merit further investigation, potentially using network meta-analysis; to inform the direction of new primary research. Any new trial should be adequately powered to detect a difference in SSIs in eligible participants, should use robust research methodology to reduce the risks of bias and internationally recognised criteria for diagnosis of SSI, and should have adequate duration and follow-up.

Leflunomide prevents ROS-induced systemic fibrosis in mice.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibrosis of the skin and inner organs, vasculopathy and immunological abnormalities. Recent insights into the polarization of macrophages in scleroderma and into the implication of STAT6 and KLF4 in this process have prompted us to investigate the effects of the inhibition of STAT6 signaling pathway by leflunomide in mice. SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) or bleomycin. Mice were treated (or not) every other day, for 4 or 6 weeks, by leflunomide. Skin and lung fibrosis as well as immunological features were studied. Mice exposed to HOCl developed a diffuse cutaneous SSc with pulmonary fibrosis and anti-DNA topoisomerase 1 auto-antibodies. STAT6 pathway was hyperactivated and KLF4 was overexpressed in the skin and the lungs of diseased mice. Their inhibition by leflunomide prevented skin and lung fibrosis. Moreover, the hyperproliferative and pro-oxidative phenotype of skin and lung fibroblasts was reversed by leflunomide. Beneficial immunological effects of leflunomide were associated with decreased activation of CD4+ and CD8+ T cells, B cell activation, decreased auto-antibodies production and restored polarization of macrophages in the spleen. The improvement provided by leflunomide in both mouse models of SSc provides a rationale for the evaluation of this immunomodulating drug in the management of patients affected by this disease.

Topical Approaches to Improve Surgical Outcomes and Wound Healing: A Review of Efficacy and Safety.

Surgical procedures are an important piece of a dermatologist's daily practice. Therefore, the optimization of post-surgical wound healing is an area of utmost importance and interest. Although low risk, one notable barrier to proper wound healing is surgical site infection.

In an attempt to mitigate this risk and improve surgical outcomes, multiple topical products continue to be used both pre- and postprocedure. Traditionally, this includes both topical antibiotics and antiseptics. However, these products are not without consequence.

The overuse of topical antibiotics as prophylaxis for infection has contributed to increased bacterial resistance, and in fact is no longer recommended by the American Academy of Dermatology in clean post surgical wounds. Topical antiseptics, including chlorhexidine and povidone-iodine, can have a cytotoxic effect on keratinocytes and may actually impede wound healing as a result. In addition, chlorhexidine in particular can produce both otologic and ocular toxic effects when used on the face. Emerging products, such as hypochlorous acid, may be a potential alternative to the more commonly used agents, as it has effective antimicrobial actions and minimal adverse effects. Therefore, the purpose of this review is to highlight several topical products used to optimize post-surgical wound healing and discuss both their efficacy and safety.

J Drugs Dermatol. 2017;16(3):209-212.

Low-concentration hypochlorous acid nasal irrigation for chronic sinonasal symptoms: a prospective randomized placebo-controlled study.

Low-concentration hypochlorous acid (HOCl) is an endogenous antibacterial and antiviral agent. The purpose of this study was to evaluate the effectiveness of HOCl irrigation in patients with chronic rhinosinusitis (CRS) refractory to medical therapy. Forty-three adult patients (mean age 45.5 years) were enrolled in this study. They were randomly chosen to receive nasal irrigation with either low-concentration HOCl generated by a Salicid device (n = 21), or a placebo (saline; n = 22) for 8 weeks. The outcome measures were scores on the 20-Item SinoNasal Outcome Test (SNOT-20), rhinosinusitis disability index (RSDI), nasal endoscopic score, and bacterial cultures. The SNOT-20 scores were significantly lower in the HOCl group than in the placebo group after 2 weeks of treatment (p < 0.05) and remained lower after 4 weeks of treatment. With respect to the RSDI scores, there was a significant improvement in the HOCl group at 1 week after treatment and in both groups at 2 weeks after treatment (p < 0.05). There were no significant differences in the endoscopic scores between the two groups after the treatment. The bacterial culture rates were lower in the HOCl group than in the placebo group after 4 weeks of treatment, but this was not significant (p > 0.05). Our results showed that low-concentration HOCl irrigation resulted in a greater improvement in CRS symptoms as compared to saline irrigation.