Ceramide-Containing Adjunctive Skin Care for Skin Barrier Restoration During Acne Vulgaris Treatment.

Barrier damage caused by facial acne vulgaris can be magnified by topical medication, such as adapalene (0.3%) and benzoyl peroxide (2.5%)(A/BPO), which utilizes a retinoid to normalize follicular keratinization and BPO to decrease the C. acnes population. Disease-induced irritation combined with topical medication-induced irritation results in dryness and enhanced inflammation leading to lower compliance and increased skin healing time. Ceramide-based moisturizers have documented barrier repair benefits for eczema but have not been studied for acne. The objective of this double-blind study was to measure the impact of acne treatment on skin barrier function and tolerance when paired with a ceramide routine. Participants were prescribed an A/BPO gel once daily. The treatment group received a ceramide-containing foaming facial cleanser and facial lotion, and the control group received basic foaming face wash for twice-daily use. Participant and investigator tolerability and efficacy were evaluated by both ordinal and clinical measures. Acne lesion counts and Investigator’s Global Assessments (IGA) of acne were obtained along with transepidermal water loss (TEWL) measurements for barrier function. TEWL for the treatment group remained significantly lower than the control at all timepoints and significantly improved from baseline by week 12. The treatment group had statistically lower mean investigator scores for dryness at all timepoints. Inflammatory lesion counts were significantly lower for the treatment group. A/BPO damaged the skin barrier, demonstrated by elevated TEWL, contributing to dryness, redness, and scaling. Use of a ceramide-containing cleanser and moisturizer significantly reduced severity and incidence of dryness, erythema, and scaling while more quickly resolving barrier damage and restoring function. Draelos ZD, Baalbaki N, Colon G, et al. Ceramide-containing adjunctive skin care for skin barrier restoration during acne vulgaris treatment. J Drugs Dermatol. 2023;22(6):554-558. doi:10.36849/JDD.7142 .

Safety, Pharmacokinetics, and Pharmacodynamics of Midazolam Gel After Rectal Administration in Healthy Chinese Subjects.

BACKGROUND AND OBJECTIVES: Midazolam rectal gel is a novel rectal formulation that may be a promising and potential alternative to oral administration for pediatric sedation. The objective of this study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and absolute bioavailability of midazolam rectal gel in healthy Chinese subjects. METHODS: An open-label, single-dose, randomized, two-period, two-treatment, crossover clinical study was conducted in 22 healthy subjects (16 males and six females), each receiving 2.5 mg intravenous midazolam in one period and 5 mg midazolam rectal gel in another period (the dosages here were calculated as active midazolam). Safety, pharmacokinetic, and pharmacodynamic assessments were conducted throughout the study. RESULTS: All of the subjects completed both treatment periods. The formulation of rectal gel was well tolerated, with no serious adverse events occurring. After a single rectal dose of 5 mg midazolam rectal gel, it was absorbed rapidly with a median value of time to peak concentration (Tmax) of 1.00 h, and mean values of the peak concentration (Cmax) and area under the concentration-time curve (AUC0-t) of 37.2 ng/mL and 137 h·ng/mL, respectively. The absolute bioavailability of rectal gel was 59.7%. The rectal gel exhibited a relatively delayed onset but a more stable sedative effect and a longer duration when compared with intravenous midazolam. CONCLUSION: Midazolam rectal gel may be a feasible alternative with a high level of acceptance in pediatric sedation and enhanced bioavailability compared to an oral formulation. The modeling results may help to disclose out the exposure-response relationship of midazolam rectal gel and support the design of an escalating-doses study and pediatric extrapolation study. CLINICAL TRIAL REGISTRATION: The study was registered at http://www.chinadrugtrials.org.cn (No. CTR20192350).

The impact of dysphagia in Parkinson's disease patients treated with levodopa/carbidopa intestinal gel.

BACKGROUND: Dysphagia is common in advanced phases of Parkinson disease (PD), and is a risk factor for aspiration pneumonia. Nonetheless, dysphagia has been poorly investigated in PD patients treated with levodopa-carbidopa intestinal gel (LCIG). We aimed to analyze the impact of dysphagia on mortality in LCIG treated patients and its relationship with other PD disability milestones. METHODS: We retrospectively evaluated 95 consecutive PD patients treated with LCIG. Kaplan-Meier and log-rank test were used to compare mortality in patients with dysphagia from others. Cox regression was used to estimate the impact of dysphagia, age, disease duration, and Hoehn and Yahr (H&Y) on mortality in the entire cohort. Finally, univariate and multivariate regression analyses were used to estimate the association between dysphagia and age, disease duration, H&Y, hallucinations, and dementia. RESULTS: A significantly higher mortality rate was observed in patients with dysphagia. In the Cox model, dysphagia was the only feature significantly associated with mortality (95%CI 2.780-20.609; p < 0.001). Univariate analyses showed a significant correlation between dysphagia and dementia (OR: 0.387; p:0.033), hallucinations (OR: 0.283; p:0.009), and H&Y score (OR: 2.680; p < 0.001); in the multivariate analysis, only the H&Y stage was associated with the presence of dysphagia (OR: 2.357; p:0.003). CONCLUSION: Dysphagia significantly increased the risk of death in our cohort of LCIG-treated patients, independently from other relevant features such as age, disease duration, dementia, and hallucinations. These findings support the management of this symptom as a priority in the advanced PD stages, even in people treated with LCIG.

Effect of an experimental desensitizing gel on bleaching-induced tooth sensitivity after in-office bleaching-a double-blind, randomized controlled trial.

OBJECTIVES: To evaluate the risk and intensity of tooth sensitivity (TS), and the efficacy of in-office bleaching after applying an experimental desensitizing gel composed of 10% calcium gluconate, 0.1% dexamethasone acetate, 10% potassium nitrate, and 5% glutaraldehyde. MATERIAL AND METHODS: In a split-mouth, double-blind, placebo-controlled study, 50 participants had their upper hemiarches randomized into experimental and placebo groups. Desensitizing and placebo gels were applied for 10 min before in-office bleaching (35% hydrogen peroxide, 1 × 50 min; two bleaching sessions; 1-week interval). TS was recorded immediately after bleaching, 1, 24, and 48 h after each session, with a 0-10 visual analogue scale (VAS) and a five-point numerical rating scale (NRS). The color was recorded in all groups at baseline, 1 week after each session, and 1 month after the end of bleaching using shade guide units (ΔSGUs) and a spectrophotometer (ΔEab, ΔE00, and ΔWID). RESULTS: Most participants (96%) felt some discomfort during treatment regardless of the study group. The odds ratio for pain was 0.65 (95% CI 0.1 to 4.1; p = 1.0). The intensity of TS did not differ between groups (p > 0.31), and it was only 0.34 VAS units lower in the experimental group. A significant color change occurred in both groups regardless of the group. CONCLUSIONS: The desensitizing experimental gel applied before in-office bleaching did not reduce the risk and the intensity of TS and did not affect color change. CLINICAL RELEVANCE: Although the experimental desensitizing agent with varying mechanisms of action did not jeopardize the color change, it did not reduce the risk or intensity of in-office bleaching. CLINICAL TRIAL REGISTRATION NUMBER: RBR-7T7D4D.

Ten-year trends of the characteristics in patients with advanced Parkinson's disease at the time of intestinal gel therapy introduction / Az intestinalis gél bevezetésekor rögzített jellemzok tízéves változásai elorehaladott Parkinson-kóros betegekben

Introduction: Parkinson's disease is a neurodegenerative disease, the symptoms of which can be treated reasonably well; however, therapeutic recommendations need to be refined based on the observations from everyday practice. Objective: We aimed to analyze the extent by which published expert recommendations were reflected in the manage-ment of patients with advanced Parkinson's disease, prior to the introduction of the intestinal gel. Method: Data from patients treated with levodopa-carbidopa intestinal gel were retrospectively examined. The period from 2011 to 2021 was divided into two five-year periods, prior and after the usage of the 5-2-1 rule in clinical decision-making. Results: Levodopa-carbidopa intestinal gel treatment was initiated in 150 patients during the study period. In the second five-year period, the mean age of the patients was lower and the time from diagnosis was shorter. Also, there were significantly fewer patients with peak-dose dyskinesias (p = 0.02), biphasic dyskinesias (p<0.001), and early morning akinesias (p = 0.02). Furthermore, in the last five years of the study, fewer patients were affected by delayed on (p = 0.03), no on (p = 0.02), and freezing (p = 0.01). The mean score measured on the Hoehn-Yahr scale was also lower in the second period, while the mean MMSE score was higher (p<0.001). Daily doses of levodopa were higher (p<0.01) in the second period, but with similar dosing frequency. Conclusion: Our retrospective analysis of trends during a ten-year period revealed that, in the second five-year period, levodopa-carbidopa intestinal gel was started in advanced Parkinson's disease patients with a significantly better physical and cognitive state. Compared to expert recommendations, our patients still had a more severe clinical pic -ture at the start of device-aided therapy, but acceptance of this invasive method has improved both for patients and for general practitioners and neurologists.

Investigation of the protective effect of gel incorporating Eugenia jambolana leaf extract on 5-fluorouracil-induced oral mucositis: an animal study.

PURPOSE: The study aimed to evaluate the possible preventive effect of two concentrations (3 and 5% w/w) of Eugenia jambolana (EJ) extract against 5-FU-induced mucositis. METHOD: Sixteen adult rats were separated into four groups: two control and two preventive groups. Animals in Groups 1, 2, and 3 were injected intraperitoneally with 60 mg/kg/day of 5-FU on Day 1 followed by 150 mg/kg/day on Day 5. The rats in Group 4 (negative control) were given physiological saline at the same times and doses. Furthermore, on the fifth day of the study, the cheek and sublingual mucosa were irritated by external superficial scratches using the tip of an 18-G needle, followed by the application 15 µL of 20% acetic acid, after which 3 and 5% EJ w/w gels were applied topically for animals in Groups 2 and 3, respectively. RESULTS: The weight and the mucositis scores were recorded. Antioxidant and anti-inflammatory markers and biochemical tests were analyzed. Significant differences were found between the study groups in weight loss, clinical mucositis scores, mortality rates, and antioxidant and anti-inflammatory parameters. CONCLUSION: The preventive effect of 3% gel was significant, with no mortality rate, making it an option for preventive strategies.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

TRPA1 triggers hyperalgesia and inflammation after tooth bleaching.

Hyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.

The impact of tube replacement timing during LCIG therapy on PEG-J associated adverse events: a retrospective multicenter observational study.

BACKGROUND: Levodopa-carbidopa intestinal gel (LCIG) treatment, a unique drug delivery system for patients with advanced Parkinson's disease (PD), is covered by health insurance in Japan since September 2016. Various LCIG procedure/device-associated adverse events (AEs) have been reported; however, reports on their treatment have been limited. This is the first multicenter study to clarify the frequency and timing of device-related AEs. METHODS: Between September 2016 and December 2018, 104 patients introduced to the LCIG treatment for advanced PD in 11 hospitals were included. The patients' characteristics, AEs incidence, AEs time, and tube exchange time were investigated. RESULTS: The median follow-up period was 21.5 months. Minor AE cases were 29.4%, whereas major AE cases were 43.1%. Majority of major AEs (n = 55, 94.8%) were managed with endoscopic treatment, such as tube exchange. Few severe AEs required surgical treatment (n =3, 5.2%). The mean (range) exposure to percutaneous endoscopic gastrojejunostomy (PEG-J) was 14.7 (0-33) months. One year after the LCIG treatment introduction, 55 patients (54.0%) retained the original PEG-J tube. The mean PEG-J tube exchange time was 10.8 ± 7.0 months in all patients, 11.6 ± 4.7 and 10.5 ± 7.7 months in patients with scheduled exchange and who underwent exchange due to AEs, respectively. CONCLUSIONS: Some device-related AEs occurred during the LCIG treatment; however, only few were serious, most of which could be treated with simple procedures or tube replacement with endoscopy. Therefore, the LCIG treatment is feasible and safe and is a unique treatment option for PD, requiring endoscopists' understanding and cooperation.

Foot drop after percutaneous treatment with radiopaque gelified ethanol (Discogel®) / Pie caído posterior al tratamiento percutáneo con etanol gelificado radiopaco (Discogel®)

Sciatica due to a lumbar disc herniation is a frequent symptom, between 13% and 40% of the general population will experience an episode of sciatica during their lives. Different techniques exist to treat this condition. Among them the percutaneous intradiscal Discogel®. In all the series of patients reviewed treated with Discogel®, so far, there is not any case reported with disc extrusion and significant neurological damage. We present a case of a foot drop, caused by a disc herniation after percutaneous treatment with Discogel®. We hypothesize that the pathogenic mechanism would be the increased intradiscal volume and pressure post-puncture and annulus fibrosus damage, which could produce the disc extrusion. The extrusion of Discogel® material is possible. To the best of our knowledge, this is the first reported case of this complication with this product (AU)

La ciática secundaria a una hernia discal lumbar es un síntoma frecuente; entre el 13% y el 40% de la población general experimentará un episodio de ciática durante sus vidas. Se han desarrollado diferentes técnicas para tratar esta dolencia. Entre ellas, el Discogel® intradiscal percutáneo. En todas las series revisadas de pacientes tratados con Discogel®, hasta el momento, no se ha informado ningún caso de extrusión discal ni daño neurológico importante. Presentamos un caso de pie caído, causado por una hernia de disco posterior al tratamiento percutáneo con Discogel®. Nuestro mecanismo teórico es el aumento del volumen y la presión intradiscal más el daño del anillo fibroso pospunción que podría producir una extrusión discal. La extrusión del material Discogel® es posible. Hasta donde sabemos, este es el primer caso reportado de esta complicación con este producto (AU)

Features of endoscopic procedure site reaction associated with a recently approved submucosal lifting agent.

Endoscopic resection techniques, such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), are frequently aided by injection of submucosal lifting solutions that create a plane for dissection and protect deeper mural layers. ORISE™ gel is a recently approved synthetic lifting solution that produces a localized inflammatory reaction associated with retained gel at the injection site. We describe a series of six cases of ORISE™-associated inflammatory lesions in patients who underwent endoscopic resections. Deposits comprised pale fibrillary or hyalinized eosinophilic material, depending on their age. All cases were associated with an inflammatory reaction composed of foreign-body giant cells and scattered eosinophils. ORISE™ gel extended laterally and deeply beyond residual tumors in all cases. Histochemically, the material proved to be negative for Congo Red, and mucicarmine, faint blue with Alcian blue, but positive for PAS and PAS-D. It stained blue with trichrome. Such deposits were absent in cases, wherein other widely-available lifting solutions were used. We compared ORISE™ deposits to histologically similar extracellular deposits, namely amyloid and pulse granulomata. Unlike ORISE™ material, amyloid deposits appear as waxy, more densely eosinophilic material, and stain positive with Congo Red. Amyloid demonstrated prominent intramucosal and perivascular distributions, features not seen in this series of ORISE™ deposits. Hyalinized pulse granulomata showed strong overlap with ORISE™ deposits, since they also comprise eosinophilic material associated with giant cell reaction. On the other hand, they form ribbons of glassy material in circumscribed lobules, unlike the ill-defined ORISE™ deposits. In summary, we describe the pathologic findings at injection sites in patients who underwent endoscopic procedures aided by the recently approved lifting agent, ORISE™. Pathologists should be aware of its appearance and associated reaction to avoid confusion with other common extracellular deposits seen in the gastrointestinal tract.

Ultrasound gel as a source of hospital outbreaks: Indian experience and literature review.

Purpose: Hospital outbreaks are observed increasingly worldwide with various organisms from different sources such as contaminated ultrasound gel, intravenous (IV) fluids and IV medications. Among these, ultrasound gel is one of the most commonly reported sources for Burkholderia cepacia complex (Bcc) outbreaks. In this study, we describe our experience on investigation and the management of Bcc bacteraemia outbreak due to contaminated ultrasound gel from a tertiary care centre, South India. Materials and Methods: Over a 10-day period in October 2016, seven children in our Paediatric intensive care unit (ICU) were found to have bacteraemia with Bcc isolated from their blood culture. Repeated isolation of the same organism with similar antimicrobial susceptibility pattern over a short incubation period from the same location, confirmed the outbreak. An active outbreak investigation, including environmental surveillance, was carried out to find the source and control the outbreak. Isolates were subjected to multi-locus sequence typing (MLST) and global eBURST (goeBURST) analysis. Results: Environmental surveillance revealed contaminated ultrasound gel as the source of infection. MLST and goeBURST analysis confirmed that the outbreak was caused by a novel sequence type 1362 with the same clonal complex CC517. The outbreak was controlled by stringent infection control measures, withdrawal of contaminated ultrasound gel from regular usage and implementing the practice of using ultrasonogram (USG) probe cover for USG screening and guided procedures. Conclusion: This report highlights the importance of early identification of an outbreak, prompt response of the ICU and infection control teams, sound environmental and epidemiological surveillance methods to identify the source and stringent infection control measures to control the outbreak. Contaminated ultrasound gel can be a potential source for healthcare-associated infection, which cannot be overlooked.

Autologous platelet-rich gel and continuous vacuum sealing drainage for the treatment of patients with diabetic foot ulcer: Study Protocol.

BACKGROUND: Research focusing on the efficacy of autologous platelet-rich gel (APRG) and continuous vacuum sealing drainage (CVSD) for diabetic foot ulcer (DFU) is increasing. Despite increasing knowledge on this theme, its results remain inconsistent. Thus, we will provide insight into the efficacy of APRG and CVSD for patients with DFU. METHODS: We will search electronic databases of MEDILINE, EMBASE, Cochrane Library, CINAHL, AMED, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to October 1, 2019. No language limitation is utilized to these databases. Two authors will independently perform study selection, data extraction, and risk of bias assessment. Disagreements between 2 authors will be solved through discussion with a third author. RESULTS: The efficacy and safety of APRG and CVSD for patients with DFU will be assessed by the time to complete healing, proportion of ulcers healed within trial period, change of size of ulcer, health-related quality of life, patient length of hospital stay, and adverse events. CONCLUSION: The results of this study will provide helpful evidence of APRG and CVSD for patients with DFU. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153289.

Core-Shell-Shell Nanoparticles for NIR Fluorescence Imaging and NRET Swelling Reporting of Injectable or Implantable Gels.

Injectable gels that support load are desirable for restoring the mechanical properties of degenerated load-bearing tissue. As these gels become increasingly sophisticated, the need to remotely image them and monitor their swelling increases. However, imaging such gels and monitoring their swelling using noninvasive means is challenging. Here, we use a very low concentration of near-infrared (NIR) core-shell-shell (CSS) reporter nanoparticles to both image and monitor swelling changes of two load-supporting gels. The load-supporting injectable gel consisted of covalently interlinked pH-responsive microgel (MG) particles. The latter gel was not cytotoxic and is termed a doubly cross-linked microgel (DX MG). Inclusion of a complementary fluorescent dye enabled ratiometric monitoring of gel swelling changes in response to pH via nonradiative resonance energy transfer (NRET). In addition, changes in the CSS nanoparticle emission intensity provided a NIR-only method that could also be used to monitor gel swelling. The gel was able to be imaged using NIR light, after being subcutaneously injected into a tissue model. To demonstrate versatility of our approach, CSS and the dye were included within a model implantable gel (poly(acrylamide/acrylic acid)) and fluorescent detection of swelling investigated. Because the concentrations of the reporting species were too low to affect the mechanical properties, our approach to remote gel imaging and swelling monitoring has good potential for application in injectable gels and implants.

The effects of gel-based manicure on pulse oximetry.

INTRODUCTION: Pulse oximetry is the standard monitoring technique of functional oxygen saturation (SpO2). As the use of fingernail polish has been described to alter SpO2 readings, its removal is commonly recommended prior to measurement. Gel-based manicures have gained popularity in recent years due to their attractiveness and longevity. However, the removal of gel nail polish requires a specialised procedure. Valuable time and resources can be saved if removal can be avoided. To our knowledge, there are no available studies on the effect of gel-based manicures on pulse oximetry readings. Hence, we evaluated the effect with two oximeters, using different technology and wavelength combinations. METHODS: 17 healthy female adult volunteers were recruited for this single-blind randomised controlled trial. Subjects with hypothermia, hypotension, poor plethysmographic waveform and nail pathology were excluded. Colours tested were: black, purple, navy blue, green, light blue, white, yellow, orange, pink and red. Pulse oximetry was measured at 15- and 30-second intervals using two different pulse oximeters, the Philips M1191BL and Masimo SET®. Means were compared using paired t-tests. RESULTS: Using the Masimo oximeter, light blue (ΔM = 0.97% ± 0.96%; p = 0.001) and orange (ΔM = 0.76 ± 1.17%; p = 0.016) gel nail polish resulted in a statistically significant increase from baseline SpO2 readings. With the Philips oximeter, the limits of agreement ranged from 2% for pink to 17% for black, indicating imprecision. CONCLUSION: Gel-based manicures can result in overestimations of actual readings, delaying detection of hypoxaemia. Gel nail polish should be routinely removed or an alternative monitoring technique sought.