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Protein therapeutics are essential in the treatment of various diseases, but most of them require parenteral administration. Since intravenous and subcutaneous injections are associated with discomfort and pain, other routes have been investigated including intradermal microneedle delivery. Microneedles are shorter than hypodermic needles and therefore minimize contact with pain receptors in deeper skin layers. But the differences in anatomical and physiological characteristics of dermis and subcutis can potentially result in varying protein penetration through the skin, absorption, and metabolism. This review summarizes pharmacokinetic studies that compare the administration of protein therapeutics by subcutaneous injections and different types of microneedles intradermally including hollow, dissolvable, coated, and hydrogel-forming microneedles. Across animal and human studies, hollow microneedle delivery resulted in quicker and higher peak plasma levels of proteins and comparable bioavailability to subcutaneous injections potentially due to the extensive network of lymphatic and blood vessels in the dermis. In case of dissolvable and coated microneedles, drug release kinetics depend on component materials. The dissolution of polymer excipients can slow the release and permeation of protein therapeutics at the administration site and thereby delay absorption. The understanding of drug penetration through different skin layers, its absorption into blood capillaries or lymphatics, and dermal metabolism remains limited. Additionally, the effects of these processes on the differences in pharmacokinetic profiles of proteins following intradermal microneedle administration are not well understood. Greater insights are required for the development of the next generation of intradermal microneedle biotherapeutics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The depressed volume of the forehead and temple is resolved by filler injection. However, the current method has the potential to cause pain and side effects in patients, depending on the skill of the clinician. Therefore, this study proposes a new method for safer and simpler injection using only one injection entry point., Methods: Using the novel injection method, the filler was injected into the forehead and temple regions in three unembalmed cadavers and two healthy Korean volunteers. The cannula and filler locations were identified using dissection, ultrasonography, and three-dimensional (3D) scanning., Results: Ultrasonographic images and dissection results showed that the filler injected into the cadavers was in the target layer. The cannula and filler were located on the layer as the supraperiosteal layer on the forehead and the supra deep temporal fascia layer in the temple. Finally, 3D scanning images showed that the filler was injected precisely and effectively into the forehead and temples of the volunteer who underwent the procedure., Conclusions: This method can reduce pain and minimize externally visible wounds caused by injections. The injected filler was naturally connected from the forehead to the temple and maintained for around 3 months. Additionally, it is possible to inject fillers into the forehead and temple at a constant and safe depth without requiring specific skills. It is expected that this method will become a universal method because it minimizes the burden on both patients and clinicians., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: The nasal region plays a pivotal role in both facial esthetics and functionality. The use of volumizing fillers has emerged as a potential means to enhance nasal appearance. Preliminary findings from cadaveric studies have highlighted potential risks associated with deeper needle injection, leading to cartilage damage and lateral migration of filler material. Understanding the subcutaneous tissue depth is crucial to prevent such complications and ensure safe filler placement guided by anatomical knowledge., Methods: This study aimed to employ ultrasonographic assessment to precisely measure the depth of soft tissue in the nasal area. Fifty-two participants without prior nasal surgery or filler injections underwent detailed ultrasonographic evaluation, focusing on seven key anatomical points: Glabellar, Sellion, Rhinion, between Rhinion and Pronasal, Pronasal, between Pronasal and Subnasal, and Subnasal., Results: The ultrasonographic observation revealed varying depths of subcutaneous tissue across these points: Glabellar (4.11 ± 0.79), Sellion (5.21 ± 0.97), Rhinion (2.02 ± 0.74), Rhinion to Pronasal midpoint (6.45 ± 3.1), Pronasal (9.5 ± 2.2), between Pronasal and Subnasal (8.8 ± 0.8), and Subnasal (8.5 ± 0.5)., Discussion: The discussion underscores the significance of understanding subcutaneous tissue depth in guiding needle length and approach angles during filler injections. This knowledge aids in achieving effective filling while ensuring safe placement within the subcutaneous tissue., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: If left untreated, burn injuries can deepen or progress in depth within the first 72 hours after injury as a result of increased wound inflammation, subsequently worsening healing outcomes. This can be especially detrimental to warfighters who are constrained to resource-limited environments with delayed evacuation times to higher roles of care and more effective treatment. Preventing this burn progression at the point of injury has the potential to improve healing outcomes but requires a field-deployable therapy and delivery system. Subcutaneous therapies known to treat inflammation delivered local to the wound site may prove to be one such avenue for success., Materials and Methods: Seven Yorkshire-cross swine received partial-thickness burn injuries using a previously established contact burn model. Each animal received one of the seven therapies: (1) saline, (2) heparin, (3) ibuprofen, (4) erythropoietin, (5) resolvin, (6) rapamycin, and (7) placental extract, all of which are either currently employed or are experimental in field use and indicated to treat inflammation. Treatments were delivered subcutaneously on the day of injury and 24 hours post-injury to simulate a prolonged field care scenario, before potential evacuation. Animals and wound development were observed for 28 days before euthanasia. Throughout the course of the study, wounds were observed macroscopically via non-invasive imaging. Histological analyses provided the critical metric of burn progression. Treatment success criteria were designated as the ability to prevent burn progression past 80% of the dermal depth in two of the three treated wounds, a clinically relevant metric of burn progression., Results: It was determined that the applied model successfully created reproducible partial-thickness burn injuries in this porcine study. No significant differences with regard to lateral wound size or the rate of lateral wound closure were observed in any treatments. Several treatments including resolvin, rapamycin, ibuprofen, and erythropoietin successfully reduced burn progression to less than 80% of the dermal depth in two of the three wounds, 24 hours after injury., Conclusions: This report employs an established model of porcine contact burn injury in order to test the ability of local subcutaneous delivery of therapeutics to prevent burn progression at the point of injury, via what is believed to be the inhibition of inflammation. Several treatments successfully prevented burn progression to a full-thickness injury, potentially improving wound healing outcomes in a simulated battlefield scenario. Subcutaneously administered therapies combating burn-induced inflammation at the point of injury may serve as a field-deployable treatment modality to improve warfighter recovery and return to duty., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The objective of this study was to compare the attitudes and beliefs of PCU physicians leaders in the United States versus Canada regarding the subcutaneous method in the administration of medications and hydration in order to gain a better understanding as to why variations in practice exist., Methods: This survey trial took place from November 2022 to May 2023. The MD Anderson Cancer Center institutional review board in Houston, Texas, approved this study. The participants were the physician leaders of the acute palliative care units (PCUs) in the United States and Canada. The survey comprised questions formulated by the study investigators regarding the perceived comfort, efficiency, and preference of using the subcutaneous versus the intravenous method. The consent form and survey links were emailed to the participants., Results: Sixteen PCUs were identified in the United States and 15 PCUs in Canada. Nine US and 8 Canadian physicians completed the survey. Physicians in Canada were more likely to use the subcutaneous route for administering opioids, antiemetics, neuroleptics, and hydration. They preferred subcutaneous over intravenous or intramuscular routes ( p = 0.017). Canadian physicians felt their nursing staff was more comfortable with subcutaneous administration ( p = 0.022) and that it was easier to administer ( p = 0.02). US physicians felt the intravenous route was more efficient ( p = 0.013)., Significance of Results: The study results suggest that exposure to the subcutaneous route influences a physician's perception. Further research is needed to explore ways to incorporate its use to a greater degree in the US healthcare system.

Subcutaneous (SC) administration is transforming the delivery of biopharmaceuticals, facilitating care in a variety of healthcare settings, including home self-treatment. Large-volume single SC doses have gained attention for their potential to expand therapeutic applications and improve long-term, patient-centric dosing regimens, often at a reduced SC injection frequency. However, a systematic understanding of dose volumes and frequencies for large-volume (>2.0 mL) SC biopharmaceuticals (LVSCs) is lacking. Accordingly, this study systematically reviewed clinical-stage and approved intravenous (IV) and SC biopharmaceuticals, identifying 182 LVSCs - predominantly monoclonal or bispecific antibodies - which correspond to approximately 15% of all IV and SC biopharmaceuticals. These LVSCs are designed to target cancer and a range of non-cancer chronic disease states, including autoimmune, neurological, and cardiovascular diseases. Results show that anti-cancer LVSCs ( n  = 75) typically require 5.0 to 20.0 mL doses every three weeks and are administered by healthcare professionals. In contrast, non-cancer LVSCs ( n  = 107), which are typically self-administered monthly, show more significant dosing variability, with < 5.0 mL being the predominant volume range. Furthermore, the study identified a substantial clinical pipeline of potential LVSCs, many of which are being injected at increasingly lower dosing frequencies, suggesting significant future growth in this area. Most non-cancer LVSCs are currently undergoing clinical trials via the SC route, whereas the majority of the cancer LVSCs are being administered IV and require transition to the SC route. These findings highlight the importance of developing large-volume drug delivery systems and novel formulations to reduce injection volumes. The analysis provides valuable guidance for new product development, as well as for marketing and commercialization strategies in the rapidly evolving LVSC landscape.

Objectives: To evaluate the efficacy of subcutaneous administration of dexmedetomidine/atipamezole at the Governing Vessel 20 (GV20) acupuncture point compared with other administration routes (intramuscular and intravenous) in dogs presented for orthopaedic radiographs., Materials and Methods: Prospective, randomised, blinded, controlled clinical study. Sixty-four client-owned dogs were randomly injected with 200 μg/m 2 of dexmedetomidine intramuscular (lumbar muscles) (n=20), intravenous (n=23) or subcutaneous at the GV20 point (n=21). Following radiographs, dogs received 2000 μg/m 2 of atipamezole intramuscular (n=31), or subcutaneous at the GV20 point (n=27). Degree and time to sedation and recovery were assessed using a sedation scale and a Dynamic and Interactive Visual Analog Scale (DIVAS). Clinical physiological variables and adverse events were used. Statistical linear mixed-effect models (analysis of variance) and Cox models were performed. Significance was set at P-value <0.05., Results: Sedation was insufficient to perform orthopaedic radiographs in six dogs in the intramuscular group. The time to sedation was significantly longer, and sedation scale and DIVAS scores were significantly lower in the intramuscular group. The intravenous group had significantly higher sedation scale and DIVAS scores than the GV20 group. No significant differences were observed between the intramuscular and GV20 recovery groups, although the time effect was significantly more pronounced in the GV20 recovery group., Clinical Significance: Subcutaneous administration of dexmedetomidine and atipamezole at GV20 provided effective sedation and recovery in dogs undergoing orthopaedic radiographic studies. GV20 administration provided a clinically similar level of sedation to the intravenous route, and greater and faster sedation and similar recovery to intramuscular., (© 2023 The Authors. Journal of Small Animal Practice published by John Wiley & Sons Ltd on behalf of British Small Animal Veterinary Association.)

Injectable filler is one of the most common cosmetic procedures performed annually. An aging face shows a characteristic loss of volume in the deep fat pads of the midface. The goal of midfacial rejuvenation with injectable filler is to restore lost volume, with the suborbicularis fat pad and deep medial cheek fat being the most critical areas. Filler can be instilled here with a cannula or needle with successful outcomes. However, this procedure is not without complications if proper technique and underlying anatomy are not respected., (Published by Elsevier Inc.)

Proteins are among the most common therapeutics for the treatment of diabetes, autoimmune diseases, cancer, and metabolic diseases, among others. Despite their common use, current protein therapies, most of which are injectables, have several limitations. Large proteins such as monoclonal antibodies (mAbs) suffer from poor absorption after subcutaneous injections, thus forcing their administration by intravenous injections. Even small proteins such as insulin suffer from slow pharmacokinetics which poses limitations in effective management of diabetes. Here, a deep eutectic-based delivery strategy is used to offer a generalized approach for improving protein absorption after subcutaneous injections. The lead formulation enhances absorption of mAbs after subcutaneous injections by ≈200%. The same composition also improves systemic absorption of subcutaneously injected insulin faster than Humalog, the current gold-standard of rapid acting insulin. Mechanistic studies reveal that the beneficial effect of deep eutectics on subcutaneous absorption is mediated by their ability to reduce the interactions of proteins with the subcutaneous matrix, especially collagen. Studies also confirm that these deep eutectics are safe for subcutaneous injections. Deep eutectic-based formulations described here open new possibilities for subcutaneous injections of therapeutic proteins., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Introduction: Insulin therapy plays an irreplaceable role in glycaemic control among older adults with type 2 diabetes mellitus (T2DM) and can be administered by either multiple daily injections (MDI) of insulin or by a continuous subcutaneous insulin infusion (CSII) pump. Many clinical trials have compared the effects of CSII pumps and MDI in various diabetic populations, but there has been no systematic review and meta-analysis focusing on older adults with T2DM. This study aims to determine whether the CSII pump is associated with better glycaemic control relative to the MDI in older adults with T2DM., Methods and Analysis: PubMed, Medline, Cochrane Library, Web of Science core collection, China National Knowledge Infrastructure (CNKI), Wan Fang Database, Chinese Science and Technology Journal Database (VIP) and Chinese Biomedical Literature Database (SinoMed) will be searched from inception to December 2021. Only randomised controlled trials will be included, and the language of the selected studies will be restricted to English and Chinese. Two researchers will independently screen the studies, extract data, assess the risk of bias and evaluate the quality of evidence. Any disagreement will be resolved by consensus or by a third researcher. Data analysis and synthesis will be conducted using RevMan V.5.3. Subgroup analysis, sensitivity analysis and publication bias assessment will be performed, as necessary., Ethics and Dissemination: As this study will not contain personal information, ethical approval will not be required. The results of the study will be published in a peer-reviewed journal or at relevant conference., Prospero Registration Number: CRD42021283729., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Current US Centers for Disease Control and Prevention intramuscular injection needle length guidelines for injection fo the deltoid muscle are based on weight and gender. The aims of this study are (1) to evaluate whether other biometric data (age, gender, height, weight and body mass index (BMI)) are better predictors of the thickness of the deltoid subcutaneous fat pad (DSFP) than weight and gender and (2) to evaluate the performance of the CDC weight-based needle length guidelines. This was a retrospective single center cohort study of 386 patients who underwent surveillance PET/CT between 01/01/2020 and 04/01/2021. Patient age, gender, height, weight, BMI and CT measurements of the DSFP were evaluated. DSFP was positively correlated with weight and BMI in men (r = 0.67, P < 0.001; r = 0.74, P < 0.001) and women (r = 0.69, P < 0.001; r = 0.75, P < 0.001) respectively. DSFP was negatively correlated with age in women (r =  - 0.19, P = 0.013). Age and BMI were better predictors of DSFP than weight. The best model to predict the DSFP is: [Formula: see text] A 1-inch needle is expected to reach the deltoid in 85.3% of women less than 200 pounds, and 98.6% of men less than 260 pounds. This rate differed between genders (P < 0.001, odds ratio (OR) 0.08, 95% CI (0.02, 0.29)). A 1.5-inch needle is expected to reach the deltoid in 76.7% of women greater than 200 pounds, and 75.0% of men greater than 260 pounds. Current CDC deltoid intramuscular injection needle length guidelines result in women and obese individuals being more likely to receive subcutaneous injections. Age and BMI based guidelines for needle length selection are more accurate., (© 2022. The Author(s).)

Determining feasibility and tolerability of large volume viscous subcutaneous injection may enable optimized, intuitive delivery system design. A translational early feasibility clinical study examined large volume subcutaneous injection viability, tolerability, acceptability, tissue effects and depot location for ~1, 8, and 20 cP injections at volumes up to 10 ml in the abdomen and 5 ml in the thigh in 32 healthy adult subjects. A commercial syringe pump system delivered 192 randomized, constant rate (20 µl/s) injections (6/subject) with in-line injection pressure captured versus time. Deposition location was qualified via ultrasound. Tissue effects and pain tolerability were monitored through 2 hours post-injection with corresponding Likert acceptability questionnaires administered through 72 hours. All injection conditions were feasible and well-tolerated with ≥79.3% favorable subject responses for injection site appearance and sensation immediately post-injection, increasing to ≥96.8% at 24 hours. Mean subject pain measured via 100 mm visual analog scale increased at needle insertion (6.9 mm, SD 10.8), peaked during injection (26.9 mm, SD 21.7) and diminished within 10 minutes post-removal (1.9 mm, SD 4.2). Immediate injection site wheal (90.9%) and erythema (92.6%) formation was observed with progressive although incomplete resolution through 2 hours (44.6% and 11.4% remaining, respectively). Wheal resolution occurred more rapidly at lower viscosities. Most subjects (64.5%) had no preference between abdomen and thigh. Correlations between tissue effects, injection pressure and pain were weak (Pearson's rho ± 0-0.4). The large volume injections tested, 1-20 cP viscosities up to 10 ml in the abdomen and 5 ml in the thigh, are feasible with good subject acceptability and rapid resolution of tissue effects and pain., (© 2021 Becton, Dickinson and Company. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Jawline augmentation with calcium hydroxylapatite has not yet been evaluated in a prospective study with a split-face design. This study aims to perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique., Objective: To perform the first randomized controlled, split-face study on the efficacy and safety of calcium hydroxylapatite for jawline augmentation using the needle and cannula technique., Materials and Methods: This is a single-site, randomized, evaluator-blind trial enrolling a total of 10 healthy subjects with at least Grade 1 (mild) on a 4-point Jawline Scale. One side of the face was randomized to receive 1 to 2 syringes of calcium hydroxylapatite with lidocaine (total of 3 mL) for correction of wrinkles and folds along the jawline using both the cannula and needle method, and a balancing treatment will be performed 1 month later. Blinded investigator and subject evaluations will be performed immediately after treatment and at the 30-, 60-, and 90-day visits., Results: Ten subjects were enrolled and completed the trial. There was a improvement in the degree of wrinkling and skin sagging in the 4-point Jawline Scale, with an average of a 1.3-point improvement in the scale on the day of treatment and at the Day 30 visit, which remained improved greater than baseline after 3 months as graded by blinded investigators. The Clinician Global Aesthetic Improvement Score for the treated side versus control, as assessed by blinded investigators, demonstrated a improvement with a 2.3-point improvement on the 5-point scale, and by the final visit on Day 90, most patients had a much improved appearance from baseline., Conclusion: This study demonstrates that calcium hydroxylapatite is effective and safe for restoration and augmentation of the jawline using the unique needle and cannula technique., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Previously, we have reported short term effectiveness and safety of dupilumab in Korea. In this study, we are trying to report the long-term effectiveness and safety of dupilumab in Korea. Ninety-nine patients with moderate to severe AD were analyzed. They were evaluated using Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) at baseline, week 16, 32 and 52. Efficacy outcomes showed higher improvement at 52 weeks compared with 16 weeks; high percentual reductions in EASI (88.1%), peak pruritus NRS (65.6%), POEM (67.2%), and DLQI (69.0%) compared to baseline. Proportion of patients achieving EASI 75 and 90 were 90.2% and 53.7%. POEM and DLQI had high correlation with clinical measured outcomes. In the analysis for the factors affecting achievement of EASI 90, female gender (OR 2.5), eosinophilia (OR 0.2) and elevated LDH (OR 0.07) were significantly associated. Most frequent adverse events included facial erythema (19.2%) and conjunctivitis (17.2%), which were mild/moderate and resolved during treatment. In conclusion, dupilumab treatment for 52 weeks in Korean patients with moderate-to-severe AD confirmed long term effectiveness and safety., (© 2021. The Author(s).)

Since the ancient Egyptians, people have always been worried about their physical appearance. Nowadays, for some cultures like Latin American, physical appearance depends on the context, and the concept of beauty is to have wider hips and more prominent buttocks. One way to achieve these goals is to inject foreign modelants that include some oils to modify certain body regions. Until today, the search continues to find a modelling agent that is nonteratogenic, noncarcinogenic, and not susceptible to infection and can stay at the spot where it was injected (not migration). This review is aimed at providing a brief, comprehensive assessment of the use of modeling agents and summarizes some key imaging features of filler-related complications. The topics of this review are historical data, epidemiology, classification of dermal fillers (xenografts, hyaluronic acid derivatives, autografts, homografts, synthetic materials), adverse reactions, imaging method used in the detection of injectable fillers, MRI patterns observed in complications of injectable fillers, and histological findings of immune response, treatment, and conclusions. We present several classifications of injectable fillers based on composition, degradation, and complications. Additionally, readers will find some representative cases of the most common locations of injectable fillers demonstrating their infiltrative MRI patterns., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Leslie-Marisol Gonzalez-Hermosillo et al.)

Background: Mesenchymal stem cells derived from adipose tissue have been successfully used to promote sphincter-saving anal fistula healing., Objective: The aim of this study was to evaluate the efficacy and safety of the use of autologous centrifuged adipose tissue in the healing process of cryptoglandular complex anal fistulas., Design: This is a randomized controlled trial., Settings: This study was conducted at a single center., Patients: Patients with complex perianal fistulas not associated with Crohn's disease were included. Rectovaginal fistulas were not included., Interventions: Patients were randomly allocated to receive treatment with centrifuged adipose tissue injection (experimental group) and without injection (control group) in combination with fistula surgery., Main Outcome Measures: The primary outcome was defined as the proportion of patients with complete fistula closure at 4 weeks (short-term outcome) and 6 months after surgery (long-term outcome). Healing was defined as when the external opening was closed with no perianal discharge on clinical assessment. The secondary outcome was safety that was evaluated by the analysis of adverse events up to 3 months after surgery. Pelvic MRI was performed at 3 months to assure safety and the accuracy of the clinical determination of healing. Postoperative pain, return to work/daily activities, persistent closure at 6 months, fecal incontinence, and patient satisfaction were evaluated., Results: Fifty-eight patients who received centrifuged adipose tissue injection and 58 patients who did not receive centrifuged adipose tissue injection were included in the safety and efficacy analysis. After 4 weeks, the healing rate was 63.8% in the experimental group compared with 15.5% in the control group (p < 0.001). No major adverse events were recorded. Postoperative anal pain was significantly lower in the injection group. Time taken to return to work/daily activities was significantly shorter in the experimental group (3 days) than in the control group (17 days). At 6 months, persistent closure was similar in the 2 groups (86.2% vs 81%). Fecal Incontinence Score at 6 months after surgery was identical to the preoperative score. Patient satisfaction was high in both groups., Limitations: The absence of blinding, the lack of correlation between stem cell content, and the clinical outcome were limitations of the study., Conclusions: Autologous centrifuged adipose tissue injection may represent a safe, efficacious, and inexpensive option for the treatment of complex fistula-in-ano. See Video Abstract at http://links.lww.com/DCR/B607., Clinical Trials Registration: URL: https://www.clinicaltrials.gov. Identifier: NCT04326907., Eficacia Y Seguridad Del Tratamiento De La Fstula Anal Compleja Idioptica Utilizando Tejido Adiposo Centrifugado Autlogo Que Contiene Clulas Progenitoras Un Ensayo Controlado Aleatorio: ANTECEDENTES:Las células madre mesenquimales derivadas del tejido adiposo se han utilizado con éxito para promover la curación de la fístula anal con preservación de esfínter.OBJETIVO:El objetivo de este estudio fue evaluar la eficacia y seguridad del uso de tejido adiposo autólogo centrifugado en el proceso de cicatrización de fístulas anales complejas de origen criptoglandular.DISEÑO:Ensayo controlado aleatorio.ENTORNO CLÍNICO:Estudio unicéntrico.PACIENTES:Se incluyeron pacientes con fístulas perianales complejas no asociadas a Enfermedad de Crohn. No se incluyeron las fístulas rectovaginales.INTERVENCIONES:Los pacientes fueron asignados aleatoriamente para recibir tratamiento con inyección de tejido adiposo centrifugado (grupo experimental) y sin inyección (grupo de control) en combinación con cirugía de fístula.PRINCIPALES MEDIDAS DE VALORACIÓN:El resultado primario se definió como la proporción de pacientes con cierre completo de la fístula a las 4 semanas (resultado a corto plazo) y 6 meses después de la cirugía (resultado a largo plazo). La curación se definió cuando orificio externo se cerró sin secreción perianal en la valoración clínica. El resultado secundario fue la seguridad que se evaluó mediante el análisis de los eventos adversos (EA) hasta 3 meses después de la cirugía. La resonancia magnética pélvica se realizó a los 3 meses para garantizar la seguridad y la precisión clínica de la curación. Se evaluó el dolor postoperatorio, el regreso al trabajo / actividades diarias, el cierre persistente a los 6 meses, la incontinencia fecal y la satisfacción del paciente.RESULTADOS:Cincuenta y ocho pacientes que recibieron inyección de tejido adiposo centrifugado y 58 pacientes que no recibieron inyección de tejido adiposo centrifugado se incluyeron en el análisis de seguridad y eficacia. Después de 4 semanas, la tasa de curación fue del 63,8% en el grupo experimental en comparación con el 15,5% en el grupo de control (p <0,001). No se registraron eventos adversos importantes. El dolor anal posoperatorio fue significativamente menor en el grupo de inyección. El tiempo necesario para volver al trabajo / actividades diarias fue significativamente menor en el grupo experimental (3 días) con respecto al grupo de control (17 días). A los 6 meses, el cierre persistente fue similar en los dos grupos (86,2% vs 81%). La puntuación de incontinencia fecal a los 6 meses después de la cirugía fue idéntica a la puntuación preoperatoria. La satisfacción del paciente fue muy alta en ambos grupos.LIMITACIONES:Ausencia de cegamiento, falta de correlación entre el contenido de células madre y el resultado clínico.CONCLUSIONES:La inyección de tejido adiposo centrifugado autólogo puede representar una opción segura, eficaz y económica para el tratamiento de la fístula anal compleja.Registro de ensayos clínicos: www.clinicaltrials.gov, identificador NCT04326907; No patrocinado.Consulte Video Resumen en http://links.lww.com/DCR/B607., (Copyright © The ASCRS 2021.)

This open-label, single-dose, randomized, parallel-group, 2-arm phase 1 bioequivalence (BE) study assessed the pharmacokinetics (PK), safety, and tolerability of PF-06410293 (ADL-PF), an adalimumab (ADL) biosimilar, following administration by prefilled pen (PFP) or prefilled syringe (PFS). A total of 164 healthy adult subjects were randomized (1:1) to receive ADL-PF (40 mg subcutaneously) in the lower abdomen or upper anterior thigh by PFS or PFP; 163 subjects were included in the primary PK analysis. The concentration-time profiles of the ADL-PF PFS and PFP treatment arms were similar. The 90% confidence intervals for the test/reference ratios of the primary end points (area under the serum concentration-time profile from time 0 to 2 weeks after dosing and maximum observed serum concentration) fell within the 80.00%-125.00% prespecified margin for BE. Comparable numbers of subjects experienced adverse events (AEs) between treatment groups, and injection-site pain was similar at all times and for the 2 injection-site locations. This study demonstrated the BE of ADL-PF following subcutaneous administration using either a PFS or PFP device. ADL-PF by PFS or PFP injection was well tolerated, with the distribution of AEs, including injection-site reactions, being similar between treatment arms., (© 2021 Pfizer Inc. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Objective: To assess axonal function prior to subcutaneous immunoglobulin (SCIG) therapy or placebo in relation to relapse in chronic inflammatory demyelinating polyneuropathy (CIDP) to determine whether axonal damage can predict therapy response., Methods: Relapse rates in patients from the Polyneuropathy and Treatment with Hizentra (PATH) study, where patients were treated with placebo or SCIG (IgPro20), were analyzed by baseline (post-intravenous immunoglobulin stabilization) axonal damage (≤1 mV peroneal compound muscle action potential) status., Results: In patients with non-axonal damage, relapses were significantly higher with placebo (73.0%) than IgPro20 (0.2 g/kg: 39.1%, 0.4 g/kg: 19.2%). In patients with axonal damage, IgPro20 had no effect on relapse (placebo: 25.0%, IgPro20: 0.2 g/kg: 30.0%, 0.4 g/kg: 19.4%). Patients with axonal damage relapsed significantly less on placebo versus non-axonal damage, but they also demonstrated higher baseline disability., Conclusion: Axonal damage may correspond to relapse upon treatment withdrawal; patients with axonal damage relapse less, possibly reflecting poor response to immunoglobulin therapy, while non-axonal damage patients may experience more relapse, perhaps indicating better treatment response., Significance: In CIDP patients with axonal loss, immunoglobulin therapy may not be as effective. Assessing axonal damage could help guide therapy, with immunoglobulins ideally used before substantial axonal damage arises., Competing Interests: Declaration of Competing Interest MA has no conflicts to declare. VB is a consultant to CSL Behring, Grifols, Union Chimique Belge, Takeda, Alnylam, Alexion, ArgenX, Roche and Novo-Nordisk. She serves on international scientific advisory boards for the Myasthenia Gravis Foundation of America and Guillain-Barré Syndrome/Chronic Inflammatory Demyelinating Polyneuropathy (CIDP/GBS) Foundation International, and has received research support from CSL Behring, Grifols, Union Chimique Belge, and ArgenX. H-PH received fees for consulting or serving on steering committees or advisory boards from Baxter, Bayer Healthcare, Biogen, CSL Behring, Geneuro, Kedrion, Laboratoire francais du Fractionnement et des Biotechnologies, MedImmune, Merck, Novartis, Octapharma, Receptos Celgene, Roche, and Teva, with approval by the Rector of Heinrich-Heine-University Düsseldorf. J-PL is a CSL Behring employee and biostatistician for this study. OM is an employee of CSL Behring. BLD was a CSL Behring employee during this study. All authors participated in the development and approval of this manuscript., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The present study aims to investigate the loco-regional tolerability and injection parameters (i.e., flow rate and administration volume) of an in situ forming depot (ISFD) in Göttingen minipigs, to secure both the therapeutic procedure and compliance in chronic medical prescriptions. The ISFD BEPO ® technology (MedinCell S.A.) is investigated over 10 days, after a single subcutaneous injection of test item based on a DMSO solution of diblock and triblock polyethylene glycol-polylactic acid copolymers. Injection sites are systematically observed for macroscopic loco-regional skin reactions as well as ultrasound scanning, enabling longitudinal in vivo imaging of the depot. Observations are complemented by histopathological examinations at 72 h and 240 h post-injection. Overall, no treatment-emergent adverse effects are macroscopically or microscopically observed at the subcutaneous injection sites, for the tested injection flow rates of 1 and 8 mL/min and volumes of 0.2 and 1 mL. The histopathology examination confirms an expected foreign body reaction, with an intensity depending on the injected volume. The depot morphology is similar irrespective of the administration flow rates. These results indicate that the ISFD BEPO ® technology can be considered safe when administered subcutaneously in Göttingen minipigs, a human-relevant animal model for subcutaneous administrations, in the tested ranges.

Background: Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. Several studies have been carried out to determine if speed of injection affects the amount of pain and bruising where the injection is given; however, the results of these studies have differed, and study authors have not reached a clear final conclusion. This is the second update of a review first published in 2014., Objectives: To assess the effects of duration (speed) of subcutaneous heparin injection on pain and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). We also looked at haematoma at the injection site., Search Methods: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 June 2020. We undertook reference checking of included studies to identify additional studies., Selection Criteria: We searched for randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site., Data Collection and Analysis: For this update, two review authors independently selected studies and extracted data via Covidence software and assessed methodological quality using Cochrane's risk of bias tool. The primary outcomes of interest were pain intensity at injection site and size and incidence of bruising. The secondary outcomes of interest were size and incidence of haematoma at injection site. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with corresponding 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria., Main Results: We identified one new study for this update, resulting in a total of five included studies with 503 participants who received subcutaneous injections of LMWH into the abdomen. Given the nature of the intervention, it was not possible to blind participants and caregivers (personnel) in any of the included studies. Two studies described blinding of outcome assessors. Overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds, and the duration of the slow injection was 30 seconds in all included studies. Four studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection; meta-analysis showed no evidence of a difference in site pain intensity immediately after slow injection when compared to fast injection (MD -1.52, 95% CI -3.56 to 0.53; 140 participants; low-certainty evidence). Meta-analysis of three studies indicated that site pain intensity may be slightly reduced 48 hours after the slow heparin injection compared to fast injection (MD -1.60, 95% CI -2.69 to -0.51; 103 participants; low-certainty evidence). Five studies assessed bruise size at 48 hours, and two studies assessed bruise size at 60 hours. Meta-analysis showed there may be a reduction in bruise size 48 hours (SMD -0.54, 95% CI -1.05 to -0.02; 503 participants; 5 studies; very low-certainty evidence) and 60 hours (SMD -0.49, 95% CI -0.93 to -0.06; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. There was no evidence of a difference in bruise size 72 hours after slow injection compared to fast injection (SMD -0.27, 95% CI -0.61 to 0.06; 140 participants; 2 studies; low-certainty evidence). Three studies evaluated incidence of bruising and showed there may be a reduction in bruise incidence 48 hours (OR 0.39, 95% CI 0.26 to 0.60; 444 participants; low-certainty evidence) and 60 hours (OR 0.25, 95% CI 0.10 to 0.65; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. We downgraded the certainty of the evidence due to risk of bias concerns, imprecision, and inconsistency. None of the included studies measured size or incidence of haematoma., Authors' Conclusions: Administering medication safely and enhancing patient comfort are the main aims of clinical nurses. In this review, we identified five RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity, bruise size and incidence. We found that pain may be slightly reduced 48 hours after slow injection. Similarly, there may be a reduction in bruise size and incidence after slow injection compared to fast injection 48 and 60 hours postinjection. We downgraded the certainty of the evidence for all outcomes to low or very low due to risk of bias concerns, imprecision, and inconsistency. Accordingly, new trials with a more robust design, more participants, and a focus on different injection speeds will be useful in strengthening the certainty of the available evidence., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Dermal filler injection in the vicinity of the terminal facial artery (FA) can lead to vascular compromise with devastating consequences, including tissue necrosis, blindness, and stroke., Objective: The purpose of this study was to examine lumen diameter and other anatomical features of the terminal FA relevant to dermal filler injection., Materials and Methods: Eighteen embalmed adult cadavers were dissected along the distribution of the terminal FA. Gross and microscopic measurements were taken at predetermined points in its course., Results: Mean lumen diameter was largest at the midpoint between the oral commissure and the lateral supra-alar crease (0.81 ± 0.36 mm; point P1) and smallest at the midpoint between the lateral supra-alar crease and the medial canthus (0.43 ± 0.23 mm; point P3). Mean cutaneous depth was deepest at the lateral supra-alar crease (5.06 ± 1.84 mm; point P2) and most superficial at the midpoint between the lateral supra-alar crease and the medial canthus (3.13 ± 2.07 mm; point P3)., Conclusion: The large-caliber lumen diameter of the terminal FA creates the potential for intra-arterial injection with commonly used filler needles and blunt-tipped cannulas at all points in its course in the nasolabial fold and midface., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: When performing filler injection procedures to the nasojugal groove, there is the risk of iatrogenic damage to the detoured facial artery., Objective: To determine the 3-dimensional location of the detoured facial artery., Materials and Methods: The branches of the facial arteries from 118 cadaveric hemifaces were scanned using computed tomography and reconstructed using the Mimics software program., Results: Detoured facial arteries were found in 47 of the 118 hemifaces (39.8%). Two main arterial patterns were identified: in Type I (29 of 47 cases), there were both detoured and nasolabial trunks where the facial artery originated, whereas in Type II (18 of 47 cases), there was only a detoured trunk. The detoured trunk originated 32.0 ± 5.3 mm from the midsagittal line, 5.0 ± 2.8 mm from the occlusion plane, and 5.9 ± 3.5 mm below the skin layer; the inflection of the detoured trunk was located 30.0 ± 5.6 mm laterally, 26.2 ± 4.4 mm superiorly, and 5.7 ± 2.6 mm deep. The meeting point with the inferior orbital rim plane was located 17.1 ± 3.4 mm laterally, 43.4 ± 3.1 mm superiorly, and 2.8 ± 1.7 mm deep., Conclusion: The 3-dimensional location of the detoured facial artery as reported here will help clinicians to avoid iatrogenic damage when they are performing filler injection procedures., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Although influenza vaccines are effective for reducing viral transmission and the severity of clinical symptoms, influenza viruses still induce considerable morbidity and mortality worldwide. Seasonal influenza viruses infect the upper respiratory tract initially but then often induce severe pulmonary complications in the lower respiratory tract. Therefore, influenza vaccines that prevent viral infection at both the upper and lower respiratory tracts are highly anticipated. Here, we examined whether using different vaccination routes for priming and boosting achieved protection in both regions of the respiratory tract. To this end, we used inactivated whole-virion influenza vaccines to immunize mice either subcutaneously or intranasally for both priming and boosting. Regardless of the route used for boosting, the levels of virus-specific IgG in plasma were higher in mice primed subcutaneously than those in control mice, which received PBS only. In addition, intranasal priming followed by subcutaneous boosting induced higher levels of virus-specific IgG in plasma than those in control mice. The levels of virus-specific nasal IgA were higher in mice that were primed intranasally than in control mice or in mice primed subcutaneously. Furthermore, intranasal priming but not subcutaneous priming provided protection against viral challenge in the upper respiratory tract. In addition, when coupled with subcutaneous boosting, both subcutaneous and intranasal priming protected against viral challenge in the lower respiratory tract. These results indicate that intranasal priming followed by subcutaneous boosting induces both virus-specific IgG in plasma and IgA in nasal washes and protects against virus challenge in both the upper and lower respiratory tracts. Our results will help to develop novel vaccines against influenza viruses and other respiratory viruses., Competing Interests: Declaration of competing interest Y.Y. is employed by the Research Foundation for Microbial Diseases (Osaka University, Japan). The other authors have no conflicts of interests to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

There has been an exponential growth in the number of dermatologic procedures performed over the past two decades. This surge in procedural volumes is accompanied by increasing utilization of local anesthetics. A proper technique in administering local anesthesia is necessary to minimize pain and promote comfort, as it is often regarded as the most painful part of cutaneous procedures. Pain is a psychophysiological phenomenon that involves attention, cognitive appraisal, and emotion. Sensory feedback and anxiety are two important aspects of pain perception. This article aims to introduce a novel way that minimizes pain and discomfort associated with local anesthetics. It is the authors' experience that painless injection is achievable by keeping syringes/needles out of sight, proceeding with injection without pre-procedure warning, and engaging patients in a conversation or simple tasks.

Background: To date no precise data are available for extrusion forces related to the G-prime and G-double-prime of fillers in combination with different 27G and 30G needles. Therefore, the objective of this study was to analyze extrusion forces of various product-needle-combinations containing two different 27G and two different 30G needles in combination with fillers of a wide range of elastic moduli starting from 2.0 &ndash; 166.0 Pa., Material and Methods: Four different fillers with the following elastic moduli 1.87, 11.65, 61.80, 165.50 Pa were combined with four different needles: 27G &frac12;&rdquo;, internal diameter: 0.300 &mu;m; 27G &frac12;&rdquo;, internal diameter: 0.241 &mu;m; 30G &frac12;&rdquo;, internal diameter: 0.241 &mu;m and 30G &frac12;&ldquo;, internal diameter: 0.240 &mu;m. Product-needle-combination were subjected to uni-axial mechanical testing and the respective extrusion force was measured., Results: The results of this study revealed that the G-prime and the G-double-prime of a product are statistically significantly related to their extrusion force, with higher G-prime/G-double-prime products requiring higher extrusion forces. The results additionally revealed that whether the size of the needle was described as 27G or 30G by the respective manufacturer statistically significant differences between the measured extrusion forces were detected., Conclusion: Injectors need to be aware that not every 27G/30G needle has the same extrusion force even though the external diameter is similar (27G or 30G); this might additionally influence the ability to withdraw blood during a pre-injection aspiration manoeuvre. J Drugs Dermatol. 20(5): doi:10.36849/JDD.5237.

There has been a growing and evolving research to find a treatment or a prevention against coronavirus 2019 (COVID-19). Though mass vaccination will certainly help in reducing number of COVID-19 patients, an effective therapeutic measure must be available too. Intravenous remdesivir (RDV) was the first drug receiving Food and Drug Administration (FDA) approval for the treatment of COVID-19. However, in a pandemic like COVID-19, it is essential that drug formulations are readily available, affordable and convenient to administer to every patient around the globe. In this study, we have developed a Self-injectable extended release subcutaneous injection of Remdesivir (SelfExRem) for the treatment of COVID-19. As opposed to intravenous injection, extended release subcutaneous injection has the benefits of reducing face-to-face contact, minimizing hospitalization, reducing dosing frequency and reducing overall health care cost. SelfExRem was developed using a biodegradable polymer, poly(lactic-co-glycolic acid) (PLGA), dissolved in a biocompatible vehicle. Six different batches were formulated using 2 different grades of low molecular weight PLGA and 3 different PLGA concentration. The force of injection of various polymeric solutions through 23-30-gauge needles were analyzed using a TA.XTplus texture analyzer. The time required for injection was evaluated both manually and by using an autoinjector. In vitro release of all the batches were carried out in 1% v/v tween 80 in phosphate buffer saline. The study indicated that SelfExRem developed with15% w/v PLGA(75:25) provided a steady release of drug for 48 h and may be a breakthrough approach for the treatment of COVID-19., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Subcutaneous delivery of anticoagulant therapy is a common treatment modality across multiple medical disciplines. However, postinjection complications of bruising and pain continues to be a problem that has the propensity to affect patients physically and psychologically. A review of literature revealed a set of recommended injection techniques that have shown to improve these clinical outcomes., Objectives: The project aims to utilize an evidence implementation framework to introduce evidence-based injection technique, for the reduction of postinjection complications., Methods: A best practice implementation project was administered across three adult- cardiology and cardio-thoracic general wards in Singapore from March 2018 to February 2019. The Joanna Briggs Institute (JBI)'s framework of evidence implementation was utilized to enable change. A baseline audit was carried out to ascertain existing injection practices. Guided by the latest evidence, a new subcutaneous injection workflow was created and disseminated. Follow-up audits were held at 1 and 8-month postimplementation to assess compliance to the new subcutaneous injection workflow and the sustainment of change. Data were consolidated and analysed with the aid of JBI Practical Application of Clinical Evidence System. Barriers to change were also identified and addressed with the aid of JBI's Getting Research into Practice tool., Results: A large variation of subcutaneous injection techniques was observed at the baseline audit. At 1-month postimplementation, overall compliance with the new subcutaneous injection workflow was assessed to be 73.3%. Criteria 2 and 3 of the JBI Practical Application of Clinical Evidence System audit criteria improved from the baseline values (9.1-80%; 0-93.3%). At 8-month postimplementation, compliance rate remained high (83%) following strategies to reinforce and sustain change. Participants complied to Criteria 1 at all stages of the project. Correspondingly, the incidence of bruising reduced from baseline, with a relative risk reduction of 52% (1 month) and 29% (8 months). Median pain also decreased from the baseline, with an improvement from 2.0 (1.0-3.0) to 0.0 (0.0-1.0)., Conclusion: Introduction and sustainment of change requires careful planning and execution. JBI's framework of evidence implementation is an effective model to guide this process. This project also highlighted the value of continuous learning, clinical update and practice standardization. This is especially important in the current climate of nursing mobility worldwide and the associated practice variations based on nursing education and experience.

Background: Because the anatomic mechanisms underlying the formation of the midcheek groove are unclear, treatments to date have resulted in unsatisfactory outcomes., Objective: This study investigated the anatomical foundation of the midcheek groove and evaluated appropriate treatment methods., Materials and Methods: Six cadaver hemifacial specimens were subjected to gross anatomic dissection and 6 to P45 sheet plastination. Based on the anatomic results, the area under the orbicularis oculi muscle (OOM) was selected for deep filling. Patients were evaluated by measuring 3D depth, regrading, and self-assessment., Results: The medial band was observed to be an important structure of the OOM, with the facial projection overlapping the midcheek groove trace. Two of the 6 P45 specimens were found to have compact fibroelastic bundles (CFBs) between the medial band and the dermis. Deep filling of the area under the OOM significantly reduced the depth of each section in all 34 patients (p < .001). Grades 3 and 4 midcheek grooves were downgraded distinctively. Most subjects expressed satisfaction with outcomes., Conclusion: Formation of the midcheek groove is associated with the passage of CFBs. Deep filling of the area under the OOM effectively improves the midcheek grooves., (Copyright © 2020 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Rituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case-control study., Patients and Methods: All consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test., Results: Twenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group., Conclusion: In a small case-control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To investigate the effect of different pressing time on the incidence of subcutaneous hemorrhage of low molecular weight heparin (LMWH) administration by meta-analysis. Cochrane Library, PubMed, MEDLINE, CINAHL, EMbase, Springer, EBSCO, China Biomedical Literature Database, CNKI, Wanfang Database, and VIP Database were searched. To screen the literature of randomized controlled trials with different pressing time in patients with subcutaneous LMWH injection from the establishment of the database to December 2020. The quality of the literature was evaluated and the data were extracted. Meta-analysis was performed by RevMan 5.3. A total of 17 randomized controlled trials were included. Meta-analysis showed that the bleeding rate of pressing for 5 min odds ratio (OR  =  3.89, 95% confidence interval [CI]: 2.68-5.64, P  < .05) or pressing for 10 min (OR  =  1.99, 95% CI: 1.34-2.95) was significantly lower than that of pressing for 3 min. Moreover, the bleeding rate was significantly lower in the 5 min pressing (OR  =  1.47, 95% CI: 1.18-1.82) and 10 min pressing(OR  =  2.12, 95% CI: 1.61-2.77) than in the no compression group. It is the most suitable time to press 5 min after subcutaneous LMWH injection, which can better control the incidence of bleeding.

Background: Poly-L-lactic acid (PLLA) is a biodegradable, synthetic polymer that stimulates collagen production and can improve skin quality, volume, and thickness. The current reconstitution procedure for Sculptra, a PLLA-containing injectable device involves 2 hours standing time before use., Objective: To evaluate and validate an immediate-use procedure for reconstituting a PLLA-containing injectable device., Methods and Materials: Three batches of the product were shaken for 1 minute immediately after reconstitution with 8 mL of sterile water. Different physicochemical tests including viscosity, concentration of excipients (sodium carboxymethylcellulose and mannitol), pH, and particle size distribution were performed for standing times 0, 2, 24, and 72 hours after immediate shaking, and compared with the standard 2 hours standing time before shaking. The recovery and stability of optional addition of 1 mL of 2% lidocaine hydrochloride was also assessed., Results: All physiochemical parameters evaluated were equivalent, regardless of reconstitution procedure, showing that shaking vigorously for 1 minute dissolves the excipients of the product properly without a required standing time and with no impact to the PLLA particles. There were no differences in lidocaine hydrochloride content of suspensions after 0 and 72 hours., Conclusion: The PLLA-containing product can be used immediately after reconstitution including vigorous shaking, as shown from physicochemical analyses. Optional addition of lidocaine hydrochloride is feasible. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5228.

Botulinum toxin type A (BoNTA) is a powerful neurotoxin that inhibits acetylcholine release from presynaptic vesicles. The potency and safety profile of BoNTA grant the toxin vast therapeutic potential. It has been used off-label for a variety of dermatologic conditions. This review aims to analyze published literature regarding the benefits and risks of the off-label use of BoNTA beyond facial lines, including eccrine hidrocystomas, enlarged pores, keloids and hypertrophic scars, hidradenitis suppurativa, hyperhidrosis, masseter muscle hypertrophy, and salivary gland hypertrophy, among others. A MEDLINE search from January 2000 to December 2019 was conducted on the off-label uses of botulinum toxin in dermatology.

The possible transformation of a giant congenital melanocytic nevi (GCMN) in malignant melanoma estimated from 0.05% to 40% depend on the size of the lesions. Many are the surgical procedures proposed, including: full or partial-thickness excisions, dermabrasion, curettage in the first weeks of life and laser treatment. The curettage technique has been proposed in the literature for the treatment of GCMN in the first few weeks of life and defined as a relatively atraumatic surgery procedure without general complications. The authors report the first case in the literature of embolization due to use of subcutaneous peroxide infiltration before a tardive curettage procedure in a newborn case of GCMN resulting in spastic quadriplegia with dystonic reaction. Consequently, a lawsuit, due to this medical malpractice, has been opened.

Background: The forehead is a challenging area for filler injection because of the risk of serious complications. Anatomy-based filler injection techniques help to avoid severe vascular complications., Materials and Methods: Sixty-six cadaver heads were infused with adequate lead oxide contrast through the external carotid arteries, internal carotid arteries, facial artery, and superficial temporal artery. Three-dimensional computed tomography scans were reconstructed using validated algorithms. We measured the length and arc length of "beautiful" foreheads evaluated by 3 skilled surgeons., Results: The frontal branch of the superficial temporal artery (FBSTA) was classified based on the main trunk as follows: Type I FBSTA (89.72%) took a sudden turn (89.56° ± 11.76°) once passing through the temporal crest, whereas Type II FBSTA (10.28%) barely turned (52.26° ± 6.81°) at the temporal crest. A total of 319 arteries passed through the midline in 48 cadaver heads. There were more superficial arteries (292 of 319) than deep arteries (27 of 319). The difference in the length and arc length of the forehead was 19.66 ± 4.35 mm., Conclusion: This study introduces an effective technique for forehead filler injection that minimizes the risk of filler injection and improves patient satisfaction.

Background: The BAAPS advice against Brazilian butt lift (BBL) surgery in the UK was set in October 2018. A Delphi study conducted by BAAPS highlighted the importance of defining current practice and perceptions amongst UK surgeons, as this is currently unknown., Objectives: To evaluate BAAPS members' current practice and perceptions around BBL surgery to ensure patient safety and propose better recommendations., Methods: A BAAPS-commissioned survey was emailed to all BAAPS members through an on-line link. The survey collected quantitative and qualitative information in several domains., Results: This survey received a 44% response rate. Of 102 respondents, 32 surgeons undertook BBL surgery before the BAAPS advice to halt it. There was a wide variation in actual fat volumes injected, and in perceptions of what constituted a small or large volume. Virtually all respondents (96.9%) performed only subcutaneous fat injections. There were differences in fat harvest techniques. The majority (66.7%) felt that BAAPS should maintain its recommendation against undertaking BBL surgery until further data became available. Nearly a quarter of 102 respondents (20.6%) had been treated for BBL complications, the majority as a result of surgical tourism., Conclusions: The survey provides member-reported perception and experience with regard to BBL surgery in the UK. The demand for BBL surgery and its provision should be reassessed in the UK. This information will be analysed with further national and international data to better define and shape the scope of the safety of BBL surgery in the UK. BAAPS will use such data towards the production of future guidance and support for surgeons and patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Inaccurate assessment of injected drug delivery may increase cost and morbidity or reduce efficacy. Yet currently most injections are evaluated solely by the formation of a visible wheal that might not truly estimate the actual area of effect. We hypothesized that thermal injection measurement (TIM) might verify appropriate temperature at the time of injection, as required for some temperature-sensitive vaccines and provide more accurate information about the area of delivery., Methods: 0.1 mL of either iced (n = 11) or room temperature (n = 17) methylene blue solution was injected subcutaneously in mice under anesthesia and photos taken with an iPhone 7 built-in camera and Thermal Seek Camera phone plug-in. After 5 min, true values were determined at necropsy., Results: TIM was closer in value to the measured area at necropsy than the area of the visualized skin wheal at both ice temperature and room temperature. The difference between the true value and thermal area assessment of iced solution averaged 0.15 cm 2 as compared with the difference between the true value and wheal size, which averaged 0.27 cm 2 (P = 0.04). At room temperature, this was maintained for thermal and visible wheal differences, 0.23 cm 2 and 0.65 cm 2 , respectively (P = 0.0006)., Conclusions: TIM can assess temperature at the time of injection and is more accurate than visual inspection. TIM could be applied to colorless injections and areas that are hard to visualize such as scar. As a portable phone plug-in, it might be a useful adjunct to aid the evaluation of injected drug delivery including in resource-limited settings., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: Non-Hispanic Blacks (NHB) and Hispanic/Latinos (H/L) are affected disproportionately by type 2 diabetes (T2DM) and its complications due to a myriad of reasons. Lack of diabetes education has been identified as one risk factor for poorly controlled diabetes. For persons using insulin, poor insulin administration technique can be problematic. Previous studies done demonstrating this have not been inclusive of NHB and H/L populations. As a result, this study aimed to use semi-structured interviews to examine insulin pen technique and training experience in NHB and H/L inpatients with T2DM., Design: Semi-structured interviews comprised open- and close-ended questions, and prompts were conducted until reaching saturation in NHB and H/L inpatients with at least 3 months of insulin pen use. Data was analyzed by two researchers who completed a thematic analysis., Results: Twenty semi-structured interviews were completed. Two major themes emerged from analysis included: patients prefer the insulin pen to syringes and vials and most had a lack of formal pen technique teaching., Conclusion: Although the insulin pen is a preferred modality of insulin delivery, this sampling of disparity patients demonstrates that insulin pen technique should be continually reassessed by health care providers as majority of the patients never had formal insulin pen teaching. Among those who did have training, they still made errors such as not priming the pen or shortened dwell time.

Background: Calcium hydroxylapatite (CaHA) is effective for dorsal hand rejuvenation. Higher dilutions are used for biostimulation with fewer side effects., Objective: To evaluate the efficacy and safety of 2 techniques of diluted CaHA injection for dorsal hand treatment., Methods: A prospective, evaluator-blinded study was performed to compare (side-to-side) techniques for treating the dorsum of the hands with diluted CaHA: deep fat lamina or subdermal injection. Fifteen women with aging grades between 1 and 3 on the MHGS (Merz hand grading scale) were enrolled and followed up for 24 weeks. The outcomes were a histological analysis of collagen, skin viscoelasticity, high-frequency ultrasound parameters, MHGS score, and the global aesthetic improvement scale (GAIS) score., Results: Improvement in the MHGS and GAIS scores (p < .01) was observed, with no difference between techniques (p > .05). Skin viscoelasticity measures and ultrasonography for dermal parameters improved for both treatments (p < .01). The mean total collagen density increased from the baseline for both techniques (p < .01). Pain during the procedure as well as adverse effects within the follow-up did not differ between treatments (p > .4). The overall satisfaction was 12% greater for the subdermal technique (p < .05)., Conclusion: Diluted CaHA improves the skin quality of aging hands with a safe profile, without substantial differences between the techniques.

The use of dermal fillers has increased manifold over the past decade, which has been attributed to the ever-increasing need of the population for being young. Fillers have become quite popular both among patients and treating physicians due to their quick and quite predictable results. Filler injection is a safe procedure in the hands of an experienced provider using appropriate technique. Nevertheless, various adverse effects to fillers have been reported that range from mild injection site complications, such as pain and bruising, to severe complications, like tissue necrosis, retinal artery occlusion, and infections. The esthetic provider should be aware of and be able to quickly recognize such complications, and be confident in managing them. In this article we highlight the various adverse effects noted with the use of fillers and discuss prevention and management. J Drugs Dermatol. 2020;19(9):829-832. doi:10.36849/JDD.2020.5084.

Introduction: Algeria has more than 1.7 million diabetic patients on to whom a descriptive assessment particularly on the insulin usage behaviors has not yet been initiated, although is needed. This study aims to provide a descriptive analysis of how Algerian diabetic patients perceive and apply insulin injection techniques., Methods: using the "patient" questionnaire within the Injection Technique Questionnaire (ITQ) 2016 survey, this study assessed the insulin injection practices of 100 patients recruited over a seven-month period in western Algeria at the Tlemcen University Hospital Center. The results of this study are compared to those of the ITQ 2016 survey., Results: pens are the instruments of injection for 98% of Algerians who continue to use mostly long needles of 6- and 8-mm, although 4mm needles are the recommended safer option. Insulin analogues (fast and basal) are plebiscite. Arms and thighs are the preferred injection sites; the abdomen (the preferred site elsewhere) is neglected for reasons to be investigated. The correct re-suspension technique for cloudy insulin is unknown. Extensive pen needle re-use (10+ times) for over half of the patients exposes them to both higher intramuscular (IM) injection risk and lipohypertrophy (LH). Injection training is performed in Algeria by the diabetologist., Conclusion: this study describes for the first time Algerian patients´ insulin injection technique. It highlights their skills and identifies many deficiencies which patients and professionals must correct given the issues in this area., Competing Interests: The authors declare no competing interests., (Copyright: Mohammed Nassim Boukli Hacene et al.)

Background: Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems., Methods: Twenty-three patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 - April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test., Results: 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe (p < 0.01). Side effects of methotrexate were less pronounced after the prefilled pen treatment, this difference was most prominent regarding gastrointestinal adverse events associated with the injection (p < 0.01)., Conclusion: Administration of methotrexate using the pen device is a promising way of subcutaneous methotrexate delivery in children with juvenile idiopathic arthritis, as the injection is less painful and associated with fewer side effects.

Background: Tissue fillers are generally safe and well tolerated by patients. However, complications do occur and may be very severe, such as intravascular injection (with occasional residual tissue loss, visual and neurological sequelae) and late nodularity and swelling. Methods to lessen the likelihood of complications have been the subject of much recent literature. Depth of injection has been identified as a key safety consideration., Patients/methods: The role of injection of facial filler into the muscular layer of the face is explored in this article. Literature was explored using available search facilities to study the role of injections in or around this layer in the production of significant adverse reactions., Results: A body of literature seems to suggest that injection into mimetic musculature of the face especially the musculature in the periorbital and perioral regions is prone to adverse reactions., Conclusions: Injection of agents into the perioral and periorbital mimetic muscular layer may produce, product clumping, displacement, and tendency to late nodularity and swelling. It also risks intravascular injection as compared to injection of other layers of the face. Injection into the mimetic muscles especially the sphincteric muscles should be avoided to minimize the risk of complications., (© 2020 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)