Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Efficacy and safety of a new medicated nail hydrolacquer in the treatment of adults with toenail onychomycosis: A randomised clinical trial.

BACKGROUND: A new water-soluble formulation with ciclopirox has shown a higher penetration than other ciclopirox nail lacquers currently marketed, thus providing a higher concentration of ciclopirox into the nail. OBJECTIVE: To evaluate the efficacy and safety of a new ciclopirox nail hydrolacquer compared with its vehicle and an active comparator (hydroxypropyl chitosan-based 80 mg/g ciclopirox nail lacquer) for the treatment of toenail fungal infection. METHODS: Phase III, multicenter, randomised, double-blind, clinical trial in patients with distal mild to moderate toenail onychomycosis due to dermatophyte fungi. Patients were randomised to apply topically a ciclopirox nail hydrolacquer, its vehicle or a reference product once daily for 48 weeks with a follow-up period of 4 weeks up to week 52. RESULTS: A total of 381 patients were included. No statistically significant differences were observed between patient groups in the proportion of subjects achieving a complete cure. At week 52, a higher percentage of patients in the ciclopirox nail hydrolacquer group achieved a mycological cure (negative for culture and DTS/KOH test, with results: 32.0% ciclopirox nail hydrolacquer, 23.2% vehicle and 27% reference product, respectively), and similar results were found for improvement (mycological cure and reduction of diseased nail ≥20%, with results: 27.2% ciclopirox nail hydrolacquer, 21.6% vehicle and 20.6% reference product, respectively). Regarding mycological results, only ciclopirox nail hydrolacquer demonstrated significant statistical superiority versus vehicle negativizing dermatophyte culture (p = .039) with no recurrences, relapses or re-infections in a four-week follow-up patients with complete cure. The safety profile was comparable to the vehicle and reference product and consistent with the previously reported. CONCLUSIONS: A new water-soluble formulation for a ciclopirox nail lacquer showed similar efficacy to the reference product to eradicate toenail onychomycosis and superiority in the mycological cure defined by negative culture, thus preventing reinfections and recurrences. Efficacy and safety data demonstrate the positive benefit-risk profile of this new topical antifungal preparation. [Correction added on 13 April 2023, after first online publication: The results and conclusions in the Abstract contained incorrect information and were revised in this version.].

Transungual Delivery, Anti-Inflammatory Activity, and In Vivo Assessment of a Cyclodextrin Polypseudorotaxanes Nail Lacquer.

A new cyclodextrin polypseudorotaxanes nail lacquer (Regenail®) containing biotin, methyl sulphonyl methane (MSM), and dimethylsilanediol salicylate was developed and evaluated in vitro and in vivo. The product was developed to improve nail status and diminish signs of pathological nail alterations. A reference product (Betalfatrus®) was used for comparative purposes. An in vitro permeation experiment in hooves showed high MSM and biotin absorption. The content of sulfur and silicon in hooves was also found to be higher compared with the reference product. MSM was tested in human keratinocytes, exhibiting a good cytotoxicity profile and anti-inflammatory activity by the reduction in IL-8 and TNF-α under LPS stimuli. A clinical study was performed to check product safety and efficacy against nail brittleness and alterations such as Beau's lines and onychorrhexis. A reduction in both alterations and in surface roughness without alteration of nail structure was observed, with a good level of patient acceptance and satisfaction.

Oncogénesis del pólipo endometrial. Manejo clínico a través de marcadores biomoleculares / Oncogenesis of the endometrial polyp. Clinical management through biomolecular markers

La prevalencia de los pólipos endometriales se estima entre el 7,8 y el 35% de las mujeres, siendo mayor en el estado posmenopáusico. Los pólipos endometriales se asocian con hiperplasia endometrial y carcinogénesis, con una prevalencia informada de lesiones malignas y premalignas que puede llegar al 13%. La detección de pólipos endometriales en edad peri o posmenopáusica, en pacientes sintomáticas o asintomáticas, requiere un examen histeroscópico meticuloso. No está claro si la polipectomía debe realizarse de forma rutinaria en pacientes asintomáticas. El manejo expectante de pólipos pequeños y asintomáticos es razonable en muchos casos. Se necesitan estudios adicionales para dilucidar si los pólipos endometriales son precursores de cáncer, o simplemente marcadores de una enfermedad endometrial. Los biomarcadores capaces de detectar cambios a nivel molecular en los pólipos y el tejido endometrial nos ayudan a un mejor conocimiento y clasificación de los procesos malignos. Este conocimiento permite pasar de una medicina intervencionista a una medicina más conservadora, basada en la confianza de un conocimiento más preciso de los procesos biomoleculares. GynEC®-DX se basa en determinar la expresión de genes que se combinan en un algoritmo matemático diagnóstico para llegar a un diagnóstico negativo o positivo de cáncer de endometrio. La prueba molecular tiene un valor predictivo negativo del 99,6%, con una alta especificidad y sensibilidad. Esta prueba podría usarse para el diagnóstico diferencial del cáncer de endometrio en mujeres con pólipos endometriales sin requerir la exéresis de pólipos, limitando el riesgo iatrogénico y evitando intervenciones innecesarias

The prevalence of endometrial polyps is estimated between 7.8 and 35% of women, being more prevalent in postmenopausal women. Endometrial polyps are associated with endometrial hyperplasia and carcinogenesis, with an informed prevalence of malignant and premalignant lesions that may reach 13%. The detection of endometrial polyps in peri- or postmenopausal (status) age, in symptomatic or asymptomatic patients, requires a meticulous hysteroscopic examination. It is unclear if routine polypectomy should be performed in asymptomatic patients. The expectant management of small and asymptomatic polyps is reasonable in many cases. Additional studies are needed to elucidate whether endometrial polyps are precursors of cancer, or simply markers of an endometrial disease. Biomarkers capable of detecting changes at the molecular level in polyps and endometrial tissue help us to better understand and classify malignant processes. This knowledge allows to move from an interventional medicine to a more conservative medicine, based on the confidence of a more precise knowledge of the biomolecular processes. GynEC®-DX is based on determining the expression of genes that are combined in a diagnostic mathematical algorithm to arrive at a negative or positive diagnosis of endometrial cancer. The molecular test has a negative predictive value of 99.6%, with high specificity and sensitivity. This test could be used for the differential diagnosis of endometrial cancer in women with EPs and prevent the resection of polyps, limiting the iatrogenic risk and avoiding unnecessary interventions

Estudio observacional: seguridad de Nife-Par(R) en amenaza de parto pretérmino / Observational study: Safety of Nife-Par(R) in the threatened preterm labour

Objetivo: analizar en un estudio de forma preliminar el perfil de seguridad de nifedipino solución oral (Nife-Par(R)) en el tratamiento de la amenaza de parto prematuro. Material y métodos: análisis preliminar del estudio prospectivo y observacional de un solo brazo en mujeres con amenaza de parto pretérmino a quienes se les haya prescrito Nife-Par(R) según las indicaciones de ficha técnica. Los resultados serán contrastados con los datos de seguridad publicados sobre el uso de nifedipino en cápsulas en el trabajo de Roel de Heus y cols. Adverse drug reactions to tocolytic treatment for preterm labour: Prospective cohort study. BMJ 2009;338:b744. DOI:10.1136/bmj.b744. Resultados: en el análisis preliminar, de los 125 casos del estudio observacional con Nife-Par(R) no se ha reportado ninguna reacción adversa grave ni severa. En 6 pacientes (5%) se reportaron episodios de reacciones adversas moderadas, y en el 2,4% de las pacientes (3 casos), estas reacciones adversas provocaron la interrupción del tratamiento. Estos datos se comparan favorablemente con la literatura en la que se refieren reacciones adversas graves en 5 pacientes (1%) de 542 con el uso de nifedipino cápsulas, y un 3,1% de interrupciones de tratamiento. Conclusión: los resultados obtenidos en este estudio preliminar muestran la ausencia de reacciones adversas graves y la reducción de la intensidad, gravedad de las reacciones adversas y una reducción del 22,6% en las interrupciones de tratamiento con el uso de Nife-Par(R) respecto a lo reportado en la literatura con nifedipino cápsulas

Objective: To analyze the safety profile of nifedipine oral solution (Nife-Par(R)) compared in the treatment of threaten preterm labor. Material and methods: Preliminary analysis of the prospective, single-arm, observational study, in womensingle- arm observational study in women who have been treated with Nife-Par(R) according to the specifications of the technical data sheet. Results will be compared with published safety data on the use of nifedipine in capsules in the study by Roel de Heus et al. Adverse drug reactions to tocolytic treatment for preterm labor: prospective cohort study. BMJ 2009;338:b744. DOI:10.1136/bmj.b744. Results: In the preliminary analysis of the 125 cases of the observational study with Nife-Par(R), no severe adverse reaction or severe intensity was reported. In 6 patients (5%) episodes of adverse reactions of moderate intensity were reported, and in 2.4% of the patients (3 cases), these adverse reactions caused the discontinuation of the treatment. These data compare favorably with the literature where serious adverse reactions are reported in 5 patients (1%) of 542 with the use of nifedipine capsulesand a 3.1% of treatment discontinuation 1,2. Conclusion: The results in the present preliminary analysis show the absence of severe adverse events together with reduction of the intensity and severity of the adverse events and a 22.6% reduction on treatment discontinuation compared with that reported in the literature with nifedipine capsules

Safety, tolerability, and immunogenicity of the novel antituberculous vaccine RUTI: randomized, placebo-controlled phase II clinical trial in patients with latent tuberculosis infection.

OBJECTIVES: To evaluate the safety, tolerability and immunogenicity of three different doses (5, 25 and 50 µg) of the novel antituberculous vaccine RUTI compared to placebo in subjects with latent tuberculosis infection. METHODS AND FINDINGS: Double-blind, randomized, placebo-controlled Phase II Clinical Trial (95 patients randomized). Three different RUTI doses and placebo were tested, randomized both in HIV-positive (n = 47) and HIV-negative subjects (n = 48), after completion of one month isoniazid (INH) pre-vaccination. Each subject received two vaccine administrations, 28 Days apart. Five patients withdrew and 90 patients completed the study. Assessment of safety showed no deaths during study. Two subjects had serious adverse events one had a retinal detachment while taking INH and was not randomized and the other had a severe local injection site abscess on each arm and was hospitalized; causality was assessed as very likely and by the end of the study the outcome had resolved. All the patients except 5 (21%) patients of the placebo group (3 HIV+ and 2 HIV-) reported at least one adverse event (AE) during the study. The most frequently occurring AEs among RUTI recipients were (% in HIV+/-): injection site reactions [erythema (91/92), induration (94/92), local nodules (46/25), local pain (66/75), sterile abscess (6/6), swelling (74/83), ulcer (20/11), headache (17/22) and nasopharyngitis (20/5)]. These events were mostly mild and well tolerated. Overall, a polyantigenic response was observed, which differed by HIV- status. The best polyantigenic response was obtained when administrating 25 µg RUTI, especially in HIV-positive subjects which was not increased after the second inoculation. CONCLUSION: This Phase II clinical trial demonstrates reasonable tolerability of RUTI. The immunogenicity profile of RUTI vaccine in LTBI subjects, even being variable among groups, allows us considering one single injection of one of the highest doses in future trials, preceded by an extended safety clinical phase. TRIAL REGISTRATION: ClinicalTrials.gov NCT01136161.