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ABSTRACT Background Methods Results Conclusion The treatment of the medial infraorbital region also termed the tear trough has become increasingly popular by the use of soft tissue fillers in a minimally invasive approach using a cannula.A total of 246 tear troughs were injected and investigated originating from 123 study participants. The clinical outcome was evaluated 6 months after the treatment by independent observers based on standardized frontal images and the procedure was documented by ultrasound imaging.On average, 0.26 (0.1) cc [range: 0.08–0.32] of soft tissue filler material was injected per tear trough. Tear trough depth was before the treatment rated as 2.12 (0.4), whereas after the treatment it was 1.15 (0.4) (p < 0.001). Hyperpigmentation score was 2.19 (0.4) before the treatment, whereas after the treatment it was 1.31 (0.5) (p < 0.001). Intraorbital fat pseudo‐prolapse severity was rated before the treatment 1.88 (0.7), whereas it was rated after the treatment 1.14 (0.3) (p < 0.001). Wrinkle severity of the lower eyelid was rated before the treatment 1.51 (0.6), whereas it was rated after the treatment 1.12 (0.3) (p < 0.001).The results of this retrospectively investigated case series revealed that the conducted injection technique for treating the tear trough for medial infraorbital hollowing with a cannula provided statistically significant clinical improvement with a limited adverse events profile. The technique utilized an injection approach which was perpendicularly oriented to the longitudinal axis of the tear trough thereby “bridging the gap instead of filling the entire valley.” [ABSTRACT FROM AUTHOR]

Background: Female pattern hair loss (FPHL) is the most prevalent type of alopecia among adult women. Presently, topical minoxidil stands as the sole treatment endorsed by the FDA. Addressing cases of FPHL in individuals who develop contact dermatitis in response to minoxidil can pose a challenge for dermatologists. Objective: To assess the efficacy and safety of subcutaneous injections of Botulinum Toxin Type A (BTA) in treating FPHL. Methods: Enrolled outpatients with FPHL who exhibited an allergic reaction to minoxidil solution. Diagnosis of FPHL was established through clinical examination and trichoscopy. Inclusion criteria involved patients with no prior treatment within the last year and without any comorbidities. BTA, specifically 100 units, was mixed with 2 mL of 0.9% normal saline. Twenty injection target sites, spaced 2–3 cm apart, were symmetrically marked on the hairless area of the scalp. A dosage of five units was intradermally injected at each target site. Representative photographs and dermoscopic images of the scalp were captured before and after 3 months of treatment. Results: A total of 10 FPHL, aged between 26 and 40 years, were included. The average age was 30.3 ± 4.64 years, and all patients had a positive family history of Androgenetic Alopecia. The average duration of the disease was 3.70 ± 1.42 years. According to patients' self‐assessment, after 1 month of treatment, 10 FPHL patients reported experiencing moderate to marked improvement in symptoms related to scalp oil secretion. Three months later, dermatological assessments showed that three had mild improvement, six had no change, and one had a worsening condition. No adverse effects were observed. Conclusions: Our study suggests that the effectiveness of BTA for FPHL is limited to 3 months. However, it can be considered for tentative use after effective communication with patients. The long‐term efficacy and safety of BTA in treating FPHL require further observation and study. [ABSTRACT FROM AUTHOR]

Background: Hori's nevus is a common and challenging dermatological condition, often complicated by post‐inflammatory hyperpigmentation following treatment. Platelet‐rich plasma (PRP) has demonstrated efficacy in the treatment of hyperpigmentation disorders such as melasma and periorbital darkening. Given the benefits and minimally invasive nature of PRP treatments, exploring its application in managing Hori's nevus through further investigation is worthwhile. Aims: To evaluate the safety and effectiveness of intradermal PRP therapy for the treatment of Hori's nevus. Methods: Ten female patients received bilateral intradermal PRP injections every 2 weeks for a total of four treatments. The modified dermal pigmentation and severity index (mDPASI), mean melanin index (MI), brightening score, patient self‐assessment, and clinical photographs were evaluated at 2, 4, 8, and 12 weeks post‐treatment. Adverse events were also recorded to determine treatment safety. Results: At 12 weeks post‐treatment, mDPASI decreased 38.86%, from 0.929 ± 0.617 to 0.568 ± 0.415 (p < 0.05). The mean melanin index decreased 12.75%, from 208.650 ± 26.319 to 182.052 ± 17.028 (p < 0.05). In addition, the mean brightness score evaluated by two experts was 1.4, indicating 25–50% improvement. At the end of the study, 50% of the patients reported 50–75% improvement. Side effects included pain, mild edema, and bruising, which resolved spontaneously within 3 days. No serious side effects were found. Conclusion: Our results suggest that intradermal PRP therapy may be a safe and effective alternative for the treatment of Hori's nevus and can complement conventional interventions. However, further research with a larger sample size, control groups, and longer follow‐up is needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a chronic inflammatory disease usually associated with persistent erythema and periodic flushing. This disease is difficult to treat, and the outcomes are often unsatisfactory and prone to recurrence. In recent years, botulinum toxin has been used as a new treatment for rosacea; however, its efficacy and safety remain under discussion. Although a systematic review of the effectiveness and safety of botulinum toxin has been previously conducted by other researchers, our systematic review and meta‐analysis evaluate the efficacy of botulinum toxin from a more comprehensive and detailed perspective to provide evidence for clinicians. Methods: Any study using botulinum toxin for the treatment of rosacea was considered for the analysis. Results: A total of 22 studies were included, 9 of which were randomized controlled trials involving 720 subjects. After treatment, all studies showed varying degrees of improvement in patient signs and symptoms along with reduced Clinician's Erythema Assessment (CEA) scores. The improvement was maintained for several months, and the adverse effects were mild and self‐limiting. Conclusion: Botulinum toxin may be an effective treatment for patients with rosacea; however, further clinical evidence is needed to confirm its long‐term efficacy and side effects. The study was preregistered with Prospero (CRD42022358911). [ABSTRACT FROM AUTHOR]

Since the skin limits the distribution of intradermal vaccines, a large number of dendritic cells in the skin cannot be fully utilized to elicit a more effective immune response. Here, we loaded the antigen to the surface of the flagellate bacteria that was modified by cationic polymer, thus creating antigen-loaded flagellate bacteria (denoted as 'FB-Ag') to overcome the skin barrier and perform the active delivery of antigen in the skin. The FB-Ag showed fast speed (∼0.2 μm s−1) and strong dendritic cell activation capabilities in the skin model in vitro. In vivo, the FB-Ag promoted the spread of antigen in the skin through active movement, increased the contact between Intradermal dendritic cells and antigen, and effectively activated the internal dendritic cells in the skin. In a mouse of pulmonary metastatic melanoma and in mice bearing subcutaneous melanoma tumor, the FB-Ag effectively increased antigen-specific therapeutic efficacy and produced long-lasting immune memory. More importantly, the FB-Ag also enhanced the level of COVID-19 specific antibodies in the serum and the number of memory B cells in the spleen of mice. The movement of antigen-loaded flagellate bacteria to overcome intradermal constraints may enhance the activation of intradermal dendritic cells, providing new ideas for developing intradermal vaccines. [Display omitted] [ABSTRACT FROM AUTHOR]

IntroductionUnbearable post-hemorrhoidectomy pain is a well-documented challenge, significantly impacting patient well-being and satisfaction after surgery, often influencing patients to decline in undergoing this procedure. It is widely recognized that methylene blue has an effect of reducing inflammation and pain by reduces the production of nitric oxide and inhibiting the action potentials production in nerves. This study aims to explore the potential benefits of postoperative regional administration of methylene blue in providing extended relief from post-hemorrhoidectomy pain.MethodsThis study included 97 patients aged 18–75 undergoing hemorrhoidectomy for stage III or IV hemorrhoids. A double-blind, randomized controlled trial compared postoperative intradermal injections of 1% methylene blue to 0.5% Marcaine as the control group. Two-week follow-up assessed pain. Statistical analysis, adherence to ethical standards, and registration were conducted.ResultNo significant differences were found in baseline demographics, surgical parameters, or complications between the Methylene Blue and control groups. Intervention group remained lower in mean pain score until the 12th day. Methylene blue group reported significantly lower postoperative pain scores from days 1 to 7, with no significant differences afterward.ConclusionThis ongoing randomized controlled trial reveals the potential analgesic benefits of intradermal injection 1% methylene blue. It demonstrates comparable efficacy in reducing post-hemorrhoidectomy pain, with negligible side effects and complications.

The monkeypox epidemic, which became unusually widespread among humans in 2022, has brought awareness about the necessity of smallpox vaccination of patients in the risk groups. The modern smallpox vaccine variants are introduced either intramuscularly or by skin scarification. Intramuscular vaccination cannot elicit an active immune response, since tissues at the vaccination site are immunologically poor. Skin has evolved into an immunologically important organ in mammals; therefore, intradermal delivery of a vaccine can ensure reliable protective immunity. Historically, vaccine inoculation into scarified skin (the s.s. route) was the first immunization method. However, it does not allow accurate vaccine dosing, and high-dose vaccines need to be used to successfully complete this procedure. Intradermal (i.d.) vaccine injection, especially low-dose one, can be an alternative to the s.s. route. This study aimed to compare the s.s. and i.d. smallpox immunization routes in a mouse model when using prototypic second- and fourth-generation low-dose vaccines (104 pfu). Experiments were conducted using BALB/c mice; the LIVP or LIVP-GFP strains of the vaccinia virus (VACV) were administered into the tail skin via the s.s. or i.d. routes. After vaccination (7, 14, 21, 28, 42, and 56 days post inoculation (dpi)), blood samples were collected from the retro-orbital venous sinus; titers of VACV-specific IgM and IgG in the resulting sera were determined by ELISA. Both VACV strains caused more profound antibody production when injected via the i.d. route compared to s.s. inoculation. In order to assess the level of the elicited protective immunity, mice were intranasally infected with a highly lethal dose of the cowpox virus on 62 dpi. The results demonstrated that i.d. injection ensures a stronger protective immunity in mice compared to s.s. inoculation for both VACV variants.

Vitiligo is a common skin disease with acquired depigmentation, seriously impacting patients′ physical and mental health. With the acceleration of life rhythm and the increase in psychological stress, the incidence of vitiligo increases. Because of the complicated pathogenesis, the treatment of vitiligo is still one of the most difficult challenges in dermatology. At present, the therapeutic efficacy for vitiligo is limited although various treatment methods are available. Therefore, new therapeutic approaches still need to be explored. Psoralea corylifolia injection, a proprietary Chinese medicine, can stimulate the synthesis and transport of melanin, and promote the division and proliferation of surviving melanocytes in the epidermis and hair follicles. Hence, the Psoralea corylifolia injection-based combination therapy is expected to provide a new safe and effective treatment for vitiligo. In this paper, we review literature on Psoralea corylifolia injection for vitiligo in respect of the mechanisms, usage and adverse reactions.

Background: An intradermal injection is a medical procedure that involves administering a small amount of medication or substance into the dermal layer of the skin. This research focused on identifying the most suitable injection needle for precise intradermal administration of skin boosters. Methods: The study involved conducting intradermal injections on four cadavers and participants using a 2 mm length, 34‐gauge needle (N‐Finders, Inc., South Korea). During the cadaveric study, the polynucleotide prefilled syringe was dyed green, and an anatomist performed dissections, removing only the skin layer. Ultrasonographic observations were carried out to ensure accurate intradermal injection placement. Results: In all four cadavers, the facial injections at the anterior cheek region were precisely administered intradermally at a 30‐degree injection angle. However, the 90‐degree injection was found just below the dermal layer upon skin layer removal. Discussion: The findings suggest that using a 2 mm needle length allows for easy and convenient intradermal injections. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a common, chronic auto- immune disorder affecting a significant proportion of the population. It frequently affects the skin, musculoskeletal system, the gastrointestinal system and the eye, and is characterized by itchy red patches with scales which tend to flare in a cyclical manner. Due to the inexistence of a standardized cure for the disease, and the unsatisfactory results with the conventional drugs and treatments in use owing to the side effects and the development of drug resistance, 95% ethanolic extract of Nigella sativa was evaluated for its antipsoriatic activity. Aim: To evaluate the Antipsoriatic Activity of Ethanolic Extract of Nigella Sativa in Propranolol Induced Psoriasis in Guinea Pigs. Materials and methods Study was conducted in the central animal house in Government Thoothukudi Medical College, Thoothukudi between December 2021 and March 2022 after receiving approval by Institutional Animal Ethical Committee of Government Thoothukudi Medical College, Thoothukudi, dated – 07/06/2019. 12 guinea pigs were divided into 3 groups, with 4 animals in each group. All the three groups received 0.1mg of 1% propranolol orally on a daily basis, for 14 days. In addition to it, they also received intradermal injections 2mL of Complete Freund’s Adjuvant(CFA) once a week for two weeks. After the induction of psoriasis, Group 1 was used as positive control. Group 2 was given standard drug 0.1% Tazarotene topically for 14 days, and Group 3 was given 95% ethanolic extract of Nigella sativa applied topically for 14 days. The psoriasis severity was calculated using the Psoriasis Area and Severity Index (PASI) before and after the use of the drugs, and the antipsoriatic action of the ethanolic extract of Nigella sativa was assessed by using Mann Whitney U and Kruskal Wallis test to analyse the association between the variables with p value less than 0.05 was taken as significant. Results: Considering day 14 to be the cut off for assessing the changes in the lesion, Group 1 animals did not show any reduction in the area or severity of lesions. The group 2 animals which were treated with Tazarotene showed a rapid decline in the psoriasiform lesions with an average PASI score reduction from (5.5 to 1.5). Considering day 14 to be the cut off for assessing the changes in the lesion, Group 3 animals after being treated with topical ethanolic extract of Nigella sativa showed an appreciable reduction in the severity of the lesion with an average PASI score reduction from 5.5 to 3.25. The erythema, induration, desquamation and the surface area of the lesions were considerably diminished. Conclusion The ethanolic extract of Nigella sativa was found to have a significant antipsoriatic effect on the induced lesion, when compared with control group. [ABSTRACT FROM AUTHOR]

Vitiligo is a common skin disease with acquired depigmentation, seriously impacting patients′ physical and mental health. With the acceleration of life rhythm and the increase in psychological stress, the incidence of vitiligo increases. Because of the complicated pathogenesis, the treatment of vitiligo is still one of the most difficult challenges in dermatology. At present, the therapeutic efficacy for vitiligo is limited although various treatment methods are available. Therefore, new therapeutic approaches still need to be explored. Psoralea corylifolia injection, a proprietary Chinese medicine, can stimulate the synthesis and transport of melanin, and promote the division and proliferation of surviving melanocytes in the epidermis and hair follicles. Hence, the Psoralea corylifolia injection-based combination therapy is expected to provide a new safe and effective treatment for vitiligo. In this paper, we review literature on Psoralea corylifolia injection for vitiligo in respect of the mechanisms, usage and adverse reactions. [ABSTRACT FROM AUTHOR]

Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient who developed cutaneous sarcoidosis after receiving platelet-rich plasma (PRP) injections for aesthetic purposes. The patient had previously received PRP injections without any complications, but after receiving the COVID-19 vaccine and contracting the virus, she developed sarcoidal lesions at the injection sites. The article explores the possible relationship between COVID-19 and the development of sarcoidal reactions after PRP injections, suggesting that the immune response to the virus may contribute to the development of skin reactions. The case report highlights the need for further research on the potential side effects of PRP injections during the COVID-19 era. [Extracted from the article]

• VAX-ID, a novel drug delivery device, allowed for reliable intradermal injections. • The device was rated as easy to use by healthcare professionals. • The dead space volume of 24 µL was below the set volume of 35 µL as defined by EMA. • Piglets of 12 kg were demonstrated to be a good model to mimic human skin. The recent SARS-Cov2 pandemic and mpox health emergency have led to renewed interest in intradermal vaccination due to its dose sparing potential. Indeed, intradermal vaccination is particularly of interest for use in mass vaccination campaigns, pandemic preparedness programs, and/or for vaccines that are expensive or in short supply. Moreover, the rich immune network in the skin makes it an attractive target not only for prophylactic vaccination, but also for therapeutic vaccination, like immunotherapy and (dendritic) cell-based therapies. The aim of the current paper was to provide an overview of preclinical data generated with VAX-ID®, a novel intradermal drug delivery device, to allow assessing it performance, safety and usability. The device can overcome challenges seen with the Mantoux technique whereby the needle needs to be inserted under a shallow angle. Various parameters of VAX-ID® were evaluated, including dead-space volume, dose accuracy, penetration depth & liquid deposit in piglets, as well as usability by healthcare professionals. The device has shown to have a low dead volume and a high dose accuracy. Importantly, the device performed successful injections at a predefined depth into the dermis with a high safety profile as confirmed by visual and histological evaluation in piglets. Moreover, the device was rated as easy to use by healthcare professionals. The combined preclinical performance and usability findings indicate that VAX-ID® can provide reliable, standardized and accurate drug delivery in the dermal layer of the skin with a high ease of use. The device offers a solution for injection of various prophylactic as well as therapeutic vaccines. [ABSTRACT FROM AUTHOR]

Facial skin aging is the most visible manifestation of aging in the body. In this study, we aimed to rejuvenate aging skin via a one-time intradermal injection of autologous adipose-derived stem cells (ADSCs). Eight patients were enrolled for study. Photographs of patients taken immediately before and 1, 3, 6, and 12 months after ADSC injections were comparatively evaluated for visible skin manifestations. ADSCs were cultured from the abdominal-skin-derived subcutaneous fat tissue, and 1 × 108 cultured ADSCs were injected intradermally into the facial skin. Cultured myoblasts were incubated with the supernatant derived from ADSCs, and the effect was evaluated via glucose consumption and lactic acid production in the medium. Eight cases showed the shallowing and disappearance of wrinkles, including those of the glabella, lower eyelids, crow's feet, and forehead and nasolabial grooves, a month to several months after treatment. Double eyelids became prominent, and facial pores significantly reduced in size. These effects lasted for over one year. Myoblasts cultured in the presence of an ADSC-derived exosome were activated compared to that of ADSCs cultured without supernatant. The result supports the role of muscle in ADSC skin rejuvenation. The present study first reports that a single intradermal administration of cultured ADSCs rejuvenates aged facial skin over the course of one year. Further, patients exhibited definite double eyelids and pore shrinkage, strongly indicating the active involvement of muscle, which was supported by an in vitro study. Our study also suggested the important role of biological factors delivered from injected stem cells, although the detailed mechanism of rejuvenation effects of ADSC skin injection remains to be clarified. [ABSTRACT FROM AUTHOR]

BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease characterised by thrombocytopenia and a bleeding phenomenon. The infection can be transmitted by contact with the athlete patient's blood and/or blood-contaminated secretions. In clinical settings, nursing care of these athlete patients is inherently challenging owing to the risk of transmission of infection. CASE SUMMARY We report a rare case of an SFTS athlete patient who developed an injection-site haematoma (3 cm × 3 cm) with local oozing 72 hours after intradermal injection of piperacillin sodium and tazobactam sodium. The treatment was aimed at stopping the bleeding, resolution of haematoma to relieve pain and prevention of infection to medical personnel. The athlete patient was isolated in a single room. An elastic bandage was applied locally to stop the bleeding, and the forearm was elevated. After the cessation of bleeding, freshly-cut thin potato slices were applied externally and wrapped with plastic wrap during the day, whereas 3M hydrophilic dressing was applied externally at night. With this treatment method (new triple therapy), the athlete patient's haematoma dissipated and the skin healed after one week. CONCLUSION The novel triple therapy for post-injection haematoma in an athlete patient with SFTS was found to be convenient, safe and effective. [ABSTRACT FROM AUTHOR]

Objective:To examine the effect of intradermal local anesthetic (LA) injection as an adjunct to physical therapy and rehabilitation (PTR) on pain and functionality in patients with persistent spinal pain syndrome type 2 (PSPS-T2).Materials and Methods:A total of 80 patients aged between 18 and 75 years were included and randomized in this prospective, randomized, single-blind study. The first group (n=40) received PTR, while the second group received 3-sessions of intradermal LA injection at painful locations and scar areas in addition to PTR. Patients were assessed using the visual analog scale (VAS), Oswestry Disability index (ODI), Hospital Anxiety and Depression scale (HADS), and finger to ground distance. All tools were administered before, immediately after treatment, and 1 month after completion of treatment.Results:The VAS and ODI scores were significantly reduced in both groups and were maintained at the 1-month follow-up visit. The HADS scores and finger to ground distance did not change significantly in either group (p>0.05).Conclusion:PTR was associated with improved pain and functionality in patients with PSPS-T2, with no additional therapeutic contributions from intradermal LA injections.

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy and safety of broadband light (BBL) combined with intradermal injection of tranexamic acid for treating melasma. Methods: 120 women with melasma admitted to our hospital from January 2021 to April 2022 were randomly categorized into the following groups: control group, treated with 250 mg tranexamic acid given orally twice daily, except during menstruation; group I, treated with BBL (Sciton, Inc., USA) monthly; group II, received intradermal injections of tranexamic acid monthly; and group III, treated with BBL with intradermal injection of tranexamic acid monthly. Treatment in each group lasted three months. The MASI (Melasma Area Severity Index) and VISIA (Canfield VISIA Complexion Analysis) were used for evaluation. Results: After treatment course, MASI scores and VISIA brown spot and red zone ranking improved in all four groups (p < 0.05). The decrease in MASI scores and improvement rates of VISIA brown spot and red zone rankings were not significantly different among the control group, group I, and group II; however, the decreased MASI scores and improvement rates of VISIA brown spot and red zone rankings were significantly higher in group III than in the other three groups (p < 0.05). Conclusion: The effect of BBL combined with the intradermal injection of TA in the treatment of melasma is remarkable. This combination therapy can be an alternative and effective treatment for managing melasma. [ABSTRACT FROM AUTHOR]

The current success of mRNA vaccines against COVID‐19 has highlighted the effectiveness of mRNA and DNA vaccinations. Recently, we demonstrated that a novel needle‐free pyro‐drive jet injector (PJI) effectively delivers plasmid DNA into the skin, resulting in protein expression higher than that achieved with a needle syringe. Here, we used ovalbumin (OVA) as a model antigen to investigate the potential of the PJI for vaccination against cancers. Intradermal injection of OVA‐expression plasmid DNA into mice using the PJI, but not a needle syringe, rapidly and greatly augmented OVA‐specific CD8+ T‐cell expansion in lymph node cells. Increased mRNA expression of both interferon‐γ and interleukin‐4 and an enhanced proliferative response of OVA‐specific CD8+ T cells, with fewer CD4+ T cells, were also observed. OVA‐specific in vivo killing of the target cells and OVA‐specific antibody production of both the IgG2a and IgG1 antibody subclasses were greatly augmented. Intradermal injection of OVA‐expression plasmid DNA using the PJI showed stronger prophylactic and therapeutic effects against the progression of transplantable OVA‐expressing E.G7‐OVA tumor cells. Even compared with the most frequently used adjuvants, complete Freund's adjuvant and aluminum hydroxide with OVA protein, intradermal injection of OVA‐expression plasmid DNA using the PJI showed a stronger CTL‐dependent prophylactic effect. These results suggest that the novel needle‐free PJI is a promising tool for DNA vaccination, inducing both a prophylactic and a therapeutic effect against cancers, because of prompt and strong generation of OVA‐specific CTLs and subsequently enhanced production of both the IgG2a and IgG1 antibody subclasses. [ABSTRACT FROM AUTHOR]

Background: Stem cell therapy is a promising new approach to wound healing. Stromal vascular fraction is a heterogeneous collection of cells, including adipose-derived stem cells, which are traditionally isolated using a manual collagenase-based technique. To our knowledge, this is the first human study that histologically assesses the potential of intraoperative intradermal injection of stromal vascular fraction on skin regeneration. Methods: In this controlled study, 20 patients undergoing deep inferior epigastric perforator flap breast reconstruction and bilateral flank liposuction were included. Stromal vascular fraction was injected intradermally into one side of the abdominal suture line, while the other side served as a control. Outcome measures included analysis of stromal vascular fraction by flow cytometry, histological analysis of scar tissue, and scar photography. Results: Cell yield for application and cell viability were 55.9 ± 28.5 × 106 and 75.1% ± 14.5%, respectively. Age and body mass index were positively correlated with the number of cells for application and adipose-derived stem cells. Mean vascular density, elastic fiber content, collagen maturity (scar index), epidermal thickness, and number of rete ridges all showed higher values on the treated side. Furthermore, the injected number of adipose-derived stem cells and pericytes positively correlated with vascular density. Conclusions: It is safe to speculate that intradermal stromal vascular fraction injection at the beginning of the healing process increases vascular density, collagen maturity and organization, elastic fiber content, epidermal thickness, epidermal–dermal anchoring of the scarring skin and is therefore responsible for improved skin regeneration. It is a viable and safe method that can be used as an adjunctive treatment in plastic surgery procedures where suboptimal wound healing is anticipated. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

• A cohort study of 138,264 cases was conducted in an isolated island population of 414,471. • Intradermal injection with one-fifth of the standard dosage showed no difference in vaccine efficacy. • Males who received the intradermal injection had a higher survival rate. • Booster-dosed males have a higher survival rate for COVID-19 infection than females. This study assessed the real-world relative vaccine effectiveness of the ChAdOx1/AZD1222 vaccine given intradermally at one-fifth dose compared to the standard intramuscular injection, following the completion of 2 doses of CoronaVac, due to limited vaccine availability in Thailand during the Coronavirus disease 2019 (COVID-19) pandemic. This retrospective cohort study used 138,264 records from Vachira Phuket Hospital, Phuket, Thailand. The records were divided into 2 groups: 49,387 recipients received one-fifth doses via intradermal injections, and 88,877 recipients received standard-dose intramuscular injections from September 14 to October 3, 2021, with follow-up until December 31, 2021. Relative vaccine effectiveness for the cohorts was estimated using Cox regression, adjusting for demographic and clinical risk factors. The adjusted hazard ratio between the intradermal and intramuscular groups was 0.88 (95% Confidence Interval 0.76-1.02, P = 0.09), indicating a nonsignificant protective factor for the intradermal group. Further stratified analysis revealed no significant difference between the 2 groups. The 21 and 28-day postvaccination periods minimized the possibility of confounding due to differences in the cohorts' timeframes. A booster dose of ChAdOx1/AZD1222 given intradermally at one-fifth dose did not show a significant difference compared to the standard intramuscular injection. [ABSTRACT FROM AUTHOR]

Inoculation routes may significantly affect vaccine performance due to the local microenvironment, antigen localization and presentation, and, therefore, final immune responses. In this study, we conducted a head-to-head comparison of immune response and safety of inactivated rabies vaccine inoculated via intraperitoneal (IP), intramuscular (IM), subcutaneous (SC) and needle-free injection technology-based intradermal (ID) routes in ICR mice. Immune response was assessed in terms of antigen-specific antibodies, antibody subtypes and neutralizing antibodies for up to 28 weeks. A live rabies virus challenge was also carried out to evaluate vaccine potency. The dynamics of inflammatory cell infiltration at the skin and muscle levels were determined via histopathological examination. The kinetics and distribution of a model antigen were also determined by using in vivo fluorescence imaging. Evidence is presented that the vaccine inoculated via the ID route resulted in the highest antigen-specific antibody and neutralizing antibody titers among all administration routes, while IP and IM routes were comparable, followed by the SC route. Antibody subtype analysis shows that the IP route elicited a Th1-biased immune response, while SC and IM administration elicited a prominent Th2-type immune response. Unexpectedly, the ID route leads to a balanced Th1 and Th2 immune response. In addition, the ID route conferred effective protection against lethal challenge with 40 LD50 of the rabies CVS strain, which was followed by IP and IM routes. Moreover, a one-third dose of the vaccine inoculated via the ID route provided comparable or higher efficacy to a full dose of the vaccine via the other three routes. The superior performance of ID inoculation over other routes is related to longer local retention at injection sites and higher lymphatic drainage. Histopathology examination reveals a transient inflammatory cell infiltration at ID and IM injection sites which peaked at 48 h and 24 h, respectively, after immunization, with all side effects disappearing within one week. These results suggest that needle-free injection technology-based ID inoculation is a promising strategy for rabies vaccination in regard to safety and efficacy.

Intradermal (ID) injection is a technique widely used in laboratorial and clinical applications. The boundary of the dome-like bleb formed during injection is assumed to represent the lateral extent of the injected material. This work systematically characterizes cargo molecule distribution (puddle) as a function of injection volume and molecular/particle size in rat skin post ID injection. In general, results indicate that the puddle forms a subdomain laterally contained within the bleb, with an area inversely correlating to the molecular size of the injected material. For 50 μL and 100 µL injections, the average area of the bleb was 40.97 ± 6.30 mm2 and 55.64 ± 8.20 mm2, respectively, regardless of the molecular/particle size. On the other hand, the area of the puddle was dependent on the molecular size and ranged between 45.38 ± 8.29 mm2 and 6.14 ± 4.50 mm2 for 50 µL injections, and 66.64 ± 11.22 mm2 and 11.50 ± 9.67 mm2 for 100 µL injections. The lateral distribution appears to have no time-dependency up to 10 min post injection. The trend in the depth of cargo penetration is also similar, with smaller particles extending deeper into the dermis and subcutaneous fat layers. Because the area of puddle can be significantly less than that of the bleb, establishing base characterization is essential to understand cellular interactions with the injected biological substances.

Objective: To examine the effect of intradermal local anesthetic (LA) injection as an adjunct to physical therapy and rehabilitation (PTR) on pain and functionality in patients with persistent spinal pain syndrome type 2 (PSPS-T2). Materials and Methods: A total of 80 patients aged between 18 and 75 years were included and randomized in this prospective, randomized, single-blind study. The first group (n=40) received PTR, while the second group received 3-sessions of intradermal LA injection at painful locations and scar areas in addition to PTR. Patients were assessed using the visual analog scale (VAS), Oswestry Disability index (ODI), Hospital Anxiety and Depression scale (HADS), and finger to ground distance. All tools were administered before, immediately after treatment, and 1 month after completion of treatment. Results: The VAS and ODI scores were significantly reduced in both groups and were maintained at the 1-month follow-up visit. The HADS scores and finger to ground distance did not change significantly in either group (p>0.05). Conclusion: PTR was associated with improved pain and functionality in patients with PSPS-T2, with no additional therapeutic contributions from intradermal LA injections. [ABSTRACT FROM AUTHOR]

Background: The current treatments of Facial hyperhidrosis (FH) are often limited and are associated with many adverse effects.Objective: The objective was to study the efficacy and safety of botulinum toxin-A delivery by microneedling versus its intradermal injection in the treatment of FH. Forty-two patients with FH were subjected to microneedling (Mn) followed by topical application of BTX-A on one side of the face and intra-dermal injection of BTX-A on the other side. Two sessions were performed at two week intervals. The assessment tools were Hyperhidrosis Disease Severity Scale (HDSS), the Dermatology Life Quality Index (DLQI), and patient satisfaction.Results: A score of one of HDSS was achieved in 85.7 percent of patients on the intradermally injected side versus 83.3 percent on the microneedling side (P=0.76%). Most of the patients on the injection side responded with the first session while the microneedling side responded with the second one (P<0.001). The DLQI was highly significant on both sides post-treatment (P<0.001). The side effects were mild in the form of pain on the intradermally injected sides, and mild transient erythema on the microneedling side. The microneedling side showed higher patient satisfaction compared to the intradermally injected side.Conclusion: Both techniques were safe and effective in controlling the FH. Microneedling delivery of BTX-A was less painful and had higher patient satisfaction. [ABSTRACT FROM AUTHOR]

The lower bioavailability after oral administration limited icariin applications in central nervous system. Icariin/HP-β-cyclodextrin (HP-β-CD) inclusion complex was prepared for acute severe opening traumatic brain injury (TBI) via facial intradermal (i.d.) in the mystacial pad. After fluid percussion-induced TBI, icariin/HP-β-CD at 0.4 mg/kg i.d. preserved more neurons and oligodendrocytes than intranasal injection (i.n.) or intravenous injection via tail vein (i.v.) and decreased microglia and astrocyte activation. Icariin/HP-β-CD i.d. reduced apoptosis in cortical penumbra while i.n. and i.v. showed weak or no effects. Icariin/HP-β-CD i.d. reduced Evans blue leakage and altered CD34, ZO-1, Claudin-5, and beta-catenin expression after TBI. Moreover, icariin/HP-β-CD promoted human umbilical vein endothelial cells proliferation. Thus, Icariin/HP-β-CD i.d. improved TBI, including blood–brain barrier opening. Fluorescein 5-isothiocyanate (FITC) and 3,3'-Dioctadecyloxacarbocyanine perchlorate (DiOC18(3)) mimic HP-β-CD and icariin respectively. FITC and DiOC18(3) were similarly delivered to trigeminal epineurium, perineurium and perivascular spaces or tissues, caudal dura mater, and scattered in trigeminal fasciculus, indicating that icariin/HP-β-CD was delivered to the brain via trigeminal nerve-dura mater-brain pathways. In sum, intradermal injection in mystacial pad might deliver icariin/HP-β-CD to the brain and icariin/HP-β-CD improved acute severe opening TBI. [ABSTRACT FROM AUTHOR]

Current worldwide mRNA vaccination against SARS-CoV-2 by intramuscular injection using a needled syringe has greatly protected numerous people from COVID-19. An intramuscular injection is generally well tolerated, safer and easier to perform on a large scale, whereas the skin has the benefit of the presence of numerous immune cells, such as professional antigen-presenting dendritic cells. Therefore, intradermal injection is considered superior to intramuscular injection for the induction of protective immunity, but more proficiency is required for the injection. To improve these issues, several different types of more versatile jet injectors have been developed to deliver DNAs, proteins or drugs by high jet velocity through the skin without a needle. Among them, a new needle-free pyro-drive jet injector has a unique characteristic that utilizes gunpower as a mechanical driving force, in particular, bi-phasic pyrotechnics to provoke high jet velocity and consequently the wide dispersion of the injected DNA solution in the skin. A significant amount of evidence has revealed that it is highly effective as a vaccinating tool to induce potent protective cellular and humoral immunity against cancers and infectious diseases. This is presumably explained by the fact that shear stress generated by the high jet velocity facilitates the uptake of DNA in the cells and, consequently, its protein expression. The shear stress also possibly elicits danger signals which, together with the plasmid DNA, subsequently induces the activation of innate immunity including dendritic cell maturation, leading to the establishment of adaptive immunity. This review summarizes the recent advances in needle-free jet injectors to augment the cellular and humoral immunity by intradermal injection and the possible mechanism of action.

The live attenuated varicella-zoster virus (VZV) vaccine is used for the prevention of chickenpox and herpes zoster; however, there have been few studies on the immunogenicity of intradermal vaccination. To compare the immunogenicity between subcutaneous and intradermal VZV vaccination. Thirty healthy participants aged 50–75 who developed erythema less than 10 mm in diameter in VZV skin test were examined. Thirteen participants received full dose of VZV vaccine subcutaneously and 17 participants received one-fifth dose of vaccine intradermally. Immunogenicity to VZV was determined by VZV skin test reaction, proliferation of VZV-specific memory T cells, levels of VZV-specific serum antibody, and cytokine production from peripheral blood cells. VZV skin test reaction was similar between two groups. VZV-specific memory T cells were significantly increased only in the intradermal injection group. The increase of VZV-specific memory T cells correlated with Th1, Th2 and Th17 cytokines and cytotoxic molecules. No serious adverse events were observed in either group after vaccination. Intradermal injection with one-fifth dose VZV vaccine showed a similar or greater effect on VZV-specific cellular immunostimulation than conventional subcutaneous injection. These findings suggest that one-fifth dose intradermal vaccination may have a comparable preventive effect to conventional subcutaneous injection. • There have been few studies on the immunogenicity of the intradermal VZV vaccine. • Small doses of intradermal injection had sufficient cellular immunostimulatory effect. • Intradermal injection may be more useful in preventing HZ than subcutaneous injection. [ABSTRACT FROM AUTHOR]

Under the pandemic situation, there is an urgent need to produce and acquire sufficient quantities of prophylactic vaccines. It becomes important to devise a way to achieve reliable immunity with lower doses to distribute limited supplies of vaccines to maximum number of people very quickly. Intradermal (ID) vaccination is one such method to increase the effectiveness of vaccines. However, this method has not been widely used in general clinical practice because it is technically difficult to inject vaccines precisely into the ID tissue. Therefore, new ID delivery systems that allow reliable ID administration are under development. In this paper, we summarize its design and present the results of performance and usability testing for the Immucise™ Intradermal Injection System (Immucise™). This study showed that Immucise™ can reduce dead volume and inject drugs precisely into the ID tissues of subjects from infants to the elderly and can be used correctly and safely by healthcare professionals. This randomized controlled trial compared ID administration with Immucise™ and standard subcutaneous (SC) administration of seasonal influenza vaccine by analyzing the efficacy of the vaccine in the elderly group at 90 days and 180 days after administration. It was found that the vaccine for the ID group was as effective or more effective than that for the SC group up to 180 days later. It was also found that the geometric mean titer values, especially for B strains, were higher in the two-dose ID group than in the two-dose SC group. These findings suggest that Immucise™ is one of the best devices to distribute a small amount of vaccine quickly and widely to a larger number of people with little loss of vaccine during a pandemic. [ABSTRACT FROM AUTHOR]

Abstract Introduction Intradermal injection of botulinum toxin type A (BoNT/A) has been used off-label by many clinicians for face-lifting. Previous studies on abobotulinumtoxinA (ABO) (Dysport®; Ipsen Biopharm Ltd.) have demonstrated clinical efficacy in face-lifting when compared to normal saline solution (NSS). However, few clinical studies have evaluated ABO in terms of duration of sustained effects for face-lifting. Methods Thirty subjects were enrolled, and their face was injected with ABO at a dilution of 1 vial:7 mL (500 U in 7 mL of NSS) using an intradermal injection technique. Standardized photographic documentation was obtained using a two-, and three-dimensional imaging system (Vectra H1, Canfield Scientific, Inc, Fairfield, NJ) at baseline, immediately after injection, 2 weeks after injection and at 1 , 2 , 3 , 4 , 5 and 6 months of follow-up after treatment. The face-lifting effects were graded by both the subjects and two blinded dermatologists who compared photographs taken at the different time points. Side effects were also recorded at the end of the study. Results Of the 30 subjects, 28 completed treatment and attended every follow-up visit. All subjects were female with Fitzpatrick skin type II to IV. The average age of the subjects was 27.6 ± 3.4 (range 22–34) years. The total number of ABO units used varied for each subject (range 200–250 U), with the average (± standard deviation) dose being 237 ± 19 units. Most of the subjects reported significant face-lifting up to 3 months post-procedure. However, face-lifting assessed by blinded dermatologists was notably lower than that of each patient’s evaluation. The difference in the facial contouring volume of the nasolabial fold and jawline, as measured by the Vectra H1 imaging system, was statistically significant from baseline up until 3 months after injection (p = 0.001 and p = 0.001, respectively). The only side effect found in this study was minimal bruising, which was seen in 13.8% of subjects. None of the subjects reported facial asymmetry, either at rest or during facial expression. Conclusion The results of this study demonstrate the face-lifting effect of ABO intradermal injection. The results show sustained effects up to 3 months after injection.

The invasiveness of late‐stage cutaneous squamous cell carcinoma (cSCC) is associated with poor patients' prognosis and linked to strong upregulation of the glycoprotein Podoplanin (PDPN) in cancer cells. However, the function of PDPN in these processes in cSCC carcinogenesis has not been characterized in detail yet. Employing a CRISPR/Cas9‐based loss‐of‐function approach on murine cSCC cells, we show that the loss of Pdpn results in decreased migration and invasion in vitro. Complementing these in vitro studies, labelled murine control and Pdpn knockout cells were injected orthotopically into the dermis of nude mice to recapitulate the formation of human cSCC displaying a well‐differentiated morphology with a PDPN‐positive reaction in fibroblasts in the tumor stroma. Smaller tumors were observed upon Pdpn loss, which is associated with reduced tumor cell infiltration into the stroma. Utilizing Pdpn mutants in functional experiments in vitro, we provide evidence that both the intra‐ and extracellular domains are essential for cancer cell invasion. These findings underline the critical role of PDPN in cSCC progression and highlight potential therapeutic strategies targeting PDPN‐dependent cancer cell invasion, especially in late‐stage cSCC patients. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the effectiveness and safety of tranexamic acid mesotherapy in the treatment of melasma in the Moroccan population. Materials and Methods: All the patients received an intradermal injection of tranexamic acid (5 mg/mL). No other local or general treatment was administered. The patients were kept under external photoprotection only. Pre- and post-treatment photographs were taken and analyzed with the Visioface® RD hardware. The evaluation was employed the MASI score. Results: All patients had a dark skin phototype. The average duration of melasma evolution was 3.67 years. The pre-treatment average MASI was 7.6. The post-therapeutic average MASI was 6. The Visioface® RD hardware estimated a 25% reduction in the surface area attained at month five. No serious side effects were reported. Conclusion: Tranexamic acid was proven to be an essential tool in treating melasma. [ABSTRACT FROM AUTHOR]

Background: The use of hyaluronic acid soft tissue fillers in aesthetic medicine exploded in recent years for many reasons, including being relatively safe. Incidence of delayed inflammatory reactions (DIRs) to hyaluronic acid soft tissue fillers range between 0.3% and 4.25%. These reactions are mediated by T‐lymphocytes and can be triggered by flu‐like illnesses, including SARS‐CoV‐2 infection. Vaccination may also induce hypersensitivity. Aim: In this case report, we present two cases of delayed reaction after hyaluronic acid soft tissue filler treatment of the tear trough area and following mRNA vaccination against SARS‐Cov‐2, also known as COVID‐19, months later. Patients: A 39‐year old female who previously had her tear trough area treated with hyaluronic acid soft tissue filler developed swelling days after getting the mRNA Pfizer‐BioNTech COVID‐19 vaccine. Another patient, a 61‐year‐olf female, developed intermittent facial swelling in areas previously treated with hyaluronic acid soft tissue fillers days after receiving her first dose of the mRNA Pfizer‐BioNTech COVID‐19 vaccine. Results: As demonstrated in our case report, vaccination against COVID‐19 may induce DIRs in patients who previously had hyaluronic soft tissue fillers. Conclusion: Delayed inflammatory reactions to hyaluronic acid soft tissue fillers are uncommon and usually self‐limited, with frequent spontaneous resolution. However, considering the ongoing pandemic and the worldwide demand for vaccines against COVID‐19, the aesthetic providers should be conscious of the risks posed by the interaction of such vaccines in patients who previously had or seeking hyaluronic acid soft tissue filler injections. [ABSTRACT FROM AUTHOR]

T Paolucci,1 RG Bellomo,2 MA Centra,1 N Giannandrea,1 L Pezzi,1 R Saggini11University G.d’Annunzio Chieti, Department of Medical and Oral Sciences and Biotechnologies, Chieti-Pescara, Italy; 2University of Study of Urbino Carlo Bo, Department of Biomolecular Sciences, Urbino, ItalyBackground: Mesotherapy can be included as an ancillary treatment in the management of localized pain in rehabilitation, but there are no definitive treatment protocols for this approach.Objectives: The purpose of this review was to examine new indications for more standard protocols of mesotherapy in rehabilitation.Materials and methods: This systematic review was performed using the following resources: PubMed, Cochrane, PEDro, Scopus, and Google Scholar. The following algorithm was developed, based on the PICO acronym, to evaluate the effects of mesotherapy, with pain as the primary outcome (MESH terms): [mesotherapy AND pain], [mesotherapy AND musculoskeletal], [mesotherapy AND musculoskeletal disorder], [intradermal therapy AND pain], and [intradermal therapy AND musculoskeletal disorder].Results: Seven articles (N=7) satisfied the inclusion criteria and were considered in the review: two of them treated osteoarthritis of the knee (3 sessions) and pes anserine (9 sessions) emphasizing a good efficacy of mesotherapy. Five studies analyzed spine diseases (specifically, two was about chronic and nonspecific neck pain, two about acute low back pain and one about chronic spinal pain): the results of mesotherapy treatment are encouraging both for the resolution of acute and chronic musculoskeletal vertebral pain from one to five sessions.Conclusion: Mesotherapy showed a good effect to reduce acute and chronic musculoskeletal pain and, also, it is a well-tolerated treatment. Nonetheless future randomized controlled trials should be desirable for more uniform treatment protocols.Keywords: mesotherapy, intradermal injection, rehabilitation, pain, musculoskeletal

Objectives: To conduct a systematic review of randomized controlled trials about the safety (number and severity of adverse events) and efficacy (pain reduction and functional improvement) of mesotherapy in musculoskeletal disorders, and to compare them with other therapeutic options, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Methods: A search of PubMed, Cochrane Library and Scopus database resulted in an initial total of 16,253 records. A total of 931 articles were included in the study. A final total of 7 articles, published from 1 Jan 1999 until 30 Apr 2020 were selected. Two independent reviewers selected potentially relevant studies based on the inclusion criteria for full-text reading. They evaluated the methodological quality of each study and included only studies of high methodological quality, according to the Physiotherapy Evidence Database scale. Results: Seven studies were included in the meta-analysis, and visual analogue scale scores before and after mesotherapy were considered. A statistically significant reduction in visual analogue scale score in the mesotherapy group was reported in comparison with the control group in all except 1 of the trials. Mesotherapy was found to be a safe procedure with mild and temporary side-effects, such as nausea, fatigue, numbness, sweating, headache, ecchymosis, bleeding, pain and local reaction at the injection site. Conclusion: Mesotherapy proved to be more effective than systemic therapy in the treatment of local pain and functional limitations caused by a variety of musculoskeletal conditions. However, because of the heterogeneity of the analysed studies in terms of injected drugs, administration technique, associated treatments, frequency and total number of sessions, more randomized controlled trials are needed, comparing a standardized mesotherapy protocol with a systemic treatments.

Introduction: Corticosteroid-induced rosacea-like dermatitis (CIRD) is one of the cutaneous side effects of long and excessive application of topical corticosteroids, resembling rosacea that can present with a series of cutaneous manifestations. Most patients with CIRD undergo a variety of long-term treatments before their symptoms are relieved as there is no accepted standard therapy. We gave each of seven patients two sessions of platelet-rich plasma (PRP) mesotherapy before the routine treatment to restore their skin barrier function, and we were surprised to find that the patients' symptoms and appearance were significantly improved without any further treatments. Here we report this unexpected finding in dealing with CIRD. Case Presentation: Seven patients, one male and six female, who had history of applying topical corticosteroids on the face for more than 3 months continuously or intermittently for various reasons were diagnosed with CIRD, showing varying degrees of erythema, telangiectasia, and papules, with dry skin, pain, and burning or stinging sensation. We intended to use the restorative effect of PRP to restore the skin barrier function of the patients for further treatment such as tacrolimus ointment, intense pulsed light (IPL), or pulsed dye laser (PDL), so they were treated twice with PRP intradermal injections using a mesogun injector machine. We used the VISIA skin detector to photograph and compare the changes after the treatments. Clinical efficacy was also assessed by the Global Aesthetic Improvement Scale (GAIS). Patients' assessments were recorded using three-point scale questionnaires. After two sessions of PRP treatment, before any further treatment, we were surprised to find that the patients' symptoms had improved significantly, as confirmed by VISIA skin detector and GAIS. All of the patients were satisfied with the outcomes, considering that mesotherapy was not painful and their appearance and symptoms had much improved. Conclusions: PRP mesotherapy may mitigate sensitivity and inflammation in patients with CIRD by reducing erythema, telangiectasia, and papules. It is worth conducting large randomized controlled trials to verify its safety and efficacy in treating corticosteroid-induced rosacea-like dermatitis and maybe rosacea. [ABSTRACT FROM AUTHOR]

The vaccinia virus (VACV) has been used for prophylactic immunization against smallpox for many decades. However, the VACV-based vaccine had been highly reactogenic. Therefore, after the eradication of smallpox, the World Health Organization in 1980 recommended that vaccination against this infection be discontinued. As a result, there has been a rise in the occurrence of orthopoxvirus infections in humans in recent years, with the most severe being the 2022 monkeypox epidemic that reached all continents. Thus, it is crucial to address the pressing matter of developing safe and highly immunogenic vaccines for new generations to combat orthopoxvirus infections. In a previous study, we created a LAD strain by modifying the LIVP (L) VACV strain, which is used as a first-generation smallpox vaccine in Russia. This modification involved introducing mutations in the A34R gene to enhance extracellular virion production and deleting the A35R gene to counteract the antibody response to the viral infection. In this study, a strain LADA was created with an additional deletion in the DNA of the LAD strain ati gene. This ati gene directs the production of a major non-virion immunogen. The findings indicate that the LADA VACV variant exhibits lower levels of reactogenicity in BALB/c mice during intranasal infection, as compared to the original L strain. Following intradermal immunization with a 105 PFU dose, both the LAD and LADA strains were found to induce a significantly enhanced cellular immune response in mice when compared to the L strain. At the same time, the highest level of virus-specific IFN-γ producing cells for the LAD variant was detected on the 7 th day post-immunization (dpi), whereas for LADA, it was observed on 14 dpi. The LAD and LADA strains induced significantly elevated levels of VACV-specific IgG compared to the original L strain, particularly between 28 and 56 dpi. The vaccinated mice were intranasally infected with the cowpox virus at a dose of 460 LD 50 to assess the protective immunity at 62 dpi. The LADA virus conferred complete protection to mice, with the LAD strain providing 70% protection and the parent strain L offering protection to only 60% of the animals., (Copyright ® 2024 National Research University Higher School of Economics.)

Introduction: Unbearable post-hemorrhoidectomy pain is a well-documented challenge, significantly impacting patient well-being and satisfaction after surgery, often influencing patients to decline in undergoing this procedure. It is widely recognized that methylene blue has an effect of reducing inflammation and pain by reduces the production of nitric oxide and inhibiting the action potentials production in nerves. This study aims to explore the potential benefits of postoperative regional administration of methylene blue in providing extended relief from post-hemorrhoidectomy pain., Methods: This study included 97 patients aged 18-75 undergoing hemorrhoidectomy for stage III or IV hemorrhoids. A double-blind, randomized controlled trial compared postoperative intradermal injections of 1% methylene blue to 0.5% Marcaine as the control group. Two-week follow-up assessed pain. Statistical analysis, adherence to ethical standards, and registration were conducted., Result: No significant differences were found in baseline demographics, surgical parameters, or complications between the Methylene Blue and control groups. Intervention group remained lower in mean pain score until the 12th day. Methylene blue group reported significantly lower postoperative pain scores from days 1 to 7, with no significant differences afterward., Conclusion: This ongoing randomized controlled trial reveals the potential analgesic benefits of intradermal injection 1% methylene blue. It demonstrates comparable efficacy in reducing post-hemorrhoidectomy pain, with negligible side effects and complications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Azhough, Jalali, Dashti, Taher and Aghajani.)

In vitro transcribed messenger ribonucleic acid (mRNA) constitutes an emerging therapeutic class with several clinical applications. This study presents a systematic comparison of different technologies—intradermal injection, microneedle injection, jet injection, and fractional laser ablation—for the topical cutaneous delivery of mRNA. Delivery of Cy5 labeled mRNA and non-labeled enhanced green fluorescent protein (eGFP) expressing mRNA was investigated in a viable ex vivo porcine skin model and monitored for 48 h. Forty 10 µm-thick horizontal sections were prepared from each skin sample and Cy5 labeled mRNA or eGFP expression visualized as a function of depth by confocal laser scanning microscopy and immunohistochemistry. A pixel-based method was used to create a semi-quantitative biodistribution profile. Different spatial distributions of Cy5 labeled mRNA and eGFP expression were observed, depending on the delivery modality; localization of eGFP expression pointed to the cells responsible. Delivery efficiencies and knowledge of delivery sites can facilitate development of efficient, targeted mRNA-based therapeutics.

Intradermal injection of botulinumtoxinA (BoNT/A) has been used off‐label by many clinicians for the purpose of face‐lifting effect. Some studies on AbobotulinumtoxinA (AboA) demonstrated clinical efficacy on face‐lifting effect when comparing to normal saline solution (NSS). So far, there is no split‐face comparison study on face‐lifting effect of IncobotulinumtoxinA (IncoA). The objective of this study was to compare the face‐lifting effect of IncoA intradermal injection and NSS. Twenty‐two subjects were enrolled and randomly injected with IncoA at 1:6 cc dilution (100 unit or 1 vial in 6 cc of NSS) on one side, and NSS on the other side by using intradermal injection technique. Standardized photographic documentation with 2‐, and 3‐dimentional imaging system (Vectra H1, Canfield Scientific, Inc., Fairfield, NJ) were obtained at baseline, and at 2 weeks after treatment. The face‐lifting effect was graded by the subjects and two blinded dermatologists, using photographic comparison. Side effects were also recorded at the end of the study. Immediate face‐lifting was identified on the side that was treated with IncoA by blinded injectors in 63.6% of patients. Of all subjects, 17 (77.3%) have noticed the improvement of skin laxity on the side that was treated with IncoA at 2 weeks after treatment. The difference in facial contouring volume measured by Vectra H1 imaging system on IncoA side was significantly higher (P =.033) when comparing to NSS side in patients aged <36 years old. However, there was no statistically significant difference in face‐lifting when comparing between IncoA and NSS evaluated by two blinded dermatologists (P = 1.00). Facial asymmetry was found in 36.4% of subjects. This study demonstrated the face‐lifting effect of IncoA intradermal injection. Further studies with larger number of subjects and proper method of evaluation should be done to verify these findings. [ABSTRACT FROM AUTHOR]

Introduction: Intradermal injection of botulinum toxin type A (BoNT/A) has been used off-label by many clinicians for face-lifting. Previous studies on abobotulinumtoxinA (ABO) (Dysport®; Ipsen Biopharm Ltd.) have demonstrated clinical efficacy in face-lifting when compared to normal saline solution (NSS). However, few clinical studies have evaluated ABO in terms of duration of sustained effects for face-lifting. Methods: Thirty subjects were enrolled, and their face was injected with ABO at a dilution of 1 vial:7 mL (500 U in 7 mL of NSS) using an intradermal injection technique. Standardized photographic documentation was obtained using a two-, and three-dimensional imaging system (Vectra H1, Canfield Scientific, Inc, Fairfield, NJ) at baseline, immediately after injection, 2 weeks after injection and at 1 , 2 , 3 , 4 , 5 and 6 months of follow-up after treatment. The face-lifting effects were graded by both the subjects and two blinded dermatologists who compared photographs taken at the different time points. Side effects were also recorded at the end of the study. Results: Of the 30 subjects, 28 completed treatment and attended every follow-up visit. All subjects were female with Fitzpatrick skin type II to IV. The average age of the subjects was 27.6 ± 3.4 (range 22–34) years. The total number of ABO units used varied for each subject (range 200–250 U), with the average (± standard deviation) dose being 237 ± 19 units. Most of the subjects reported significant face-lifting up to 3 months post-procedure. However, face-lifting assessed by blinded dermatologists was notably lower than that of each patient's evaluation. The difference in the facial contouring volume of the nasolabial fold and jawline, as measured by the Vectra H1 imaging system, was statistically significant from baseline up until 3 months after injection (p = 0.001 and p = 0.001, respectively). The only side effect found in this study was minimal bruising, which was seen in 13.8% of subjects. None of the subjects reported facial asymmetry, either at rest or during facial expression. Conclusion: The results of this study demonstrate the face-lifting effect of ABO intradermal injection. The results show sustained effects up to 3 months after injection. [ABSTRACT FROM AUTHOR]

The aim of this study was to fabricate Bacillus Calmette–Guérin (BCG)-loaded microneedle patches using micromould casting technique and compare their efficacy with the injectable counterparts. The microneedle patches were formulated using sodium alginate (10% w/v) and trehalose (20% of polymer). The patches were characterised using optical microscopy, scanning electron microscopy and folding endurance. Serum IgG, TLC, granulocyte count, lymphocyte count and CRP were assessed and results were compared to that of intradermal injections alongside controls. The results showed that polymeric patches had a thickness of 0.8 mm, microneedle projections of 272 ± 12 µm and folding endurance of more than 300. Based on haematological and IgG ELISA assays, microneedle-based BCG administration significantly activated the immune cells and induced production of lymphocytes, granulocytes and peptide-specific IgG in immunised rats that were comparable to injectable counterparts. There was an increase in IgG antibodies from 3 g/L to 5.98 g/L and an increase in leucocytes from 2.6 × 109/L to 18.45 × 109/L. There was also an increase in granulocytes from 14.4% to 29.15% and lymphocyte count from 58.75% to 85.3%. It was concluded that BCG-coated polymeric microneedle patches are suitable for the transdermal delivery of vaccine without inducing discomfort usually observed with injections. [ABSTRACT FROM AUTHOR]

Background: The use of platelet‐rich plasma (PRP) combined with noninvasive, nonenergy procedures for atrophic acne scars has shown promise. To date, there has not been a systematic review or meta‐analysis of the effectiveness of this therapy. Aims: To use meta‐analysis to compare Goodman and Baron qualitative scores, patient satisfaction outcomes, and adverse effects in patients undergoing combination procedures with PRP, combination procedures without PRP, and noninvasive monotherapy without PRP in the treatment of patients with atrophic acne scars. Patients/Methods: The Pubmed and Cochrane library databases were searched for relevant studies published before May 1, 2019. PRISMA guidelines were utilized. Studies that compared the use of PRP in combination with a noninvasive procedure and therapies without PRP for the treatment of atrophic acne scars were included. Cochrane's handbook was utilized to assess the individual biases of the included studies. Publication bias was assessed. Results: A total of 311 participants (153 whole‐face participants and 158 split‐face participants) were reviewed across eight included studies. Quantitative analysis of 241 participants across six included studies showed a statistically significant reduction in scar severity scores in favor of microneedling or subcision with PRP (P <.001). Combination therapy with intradermal or topical PRP was significantly more effective than monotherapy alone and combination therapy with an adjunct other than PRP (P <.001 and.001, respectively). Conclusion: This systematic review and meta‐analysis demonstrated that microneedling or subcision with PRP produced statistically significant improvement in validated outcomes over microneedling or subcision alone. [ABSTRACT FROM AUTHOR]

Introduction: Levcromakalim opens ATP-sensitive potassium channels (KATP channel) and induces head pain in healthy volunteers and migraine headache in migraine patients, but no pain in other parts of the body. KATP channels are expressed in C- and Aδ-fibers, and these channels might directly activate nociceptors and thereby evoke pain in humans.Methods: To assess the local effect of KATP channel opening in trigeminal and extra-trigeminal regions, we performed a crossover, double-blind, placebo-controlled study in healthy volunteers. Participants received intradermal and intramuscular injections of levcromakalim and placebo in the forehead and the forearms.Results: Intradermal and intramuscular injections of levcromakalim did not evoke more pain compared to placebo in the forehead (p > 0.05) and the forearms (p > 0.05). Intradermal injection of levcromakalim caused more flare (p < 0.001), skin temperature increase (p < 0.001), and skin blood flow increase (p < 0.001) compared to placebo in the forehead and the forearms.Conclusion: These findings suggest that it is unlikely that levcromakalim induces head pain by direct activation of peripheral neurons. [ABSTRACT FROM AUTHOR]

Nerve injury-induced expression of the spinal calcium channel alpha-2-delta-1 subunit (Ca(v)alpha(2)delta(1)) has been shown to mediate behavioral hypersensitivity through a yet identified mechanism. We examined if this neuroplasticity modulates behavioral hypersensitivity by regulating spinal glutamatergic neurotransmission in injury-free transgenic mice overexpressing the Ca(v)alpha(2)delta(1) proteins in neuronal tissues. The transgenic mice exhibited hypersensitivity to mechanical stimulation (allodynia) similar to the spinal nerve ligation injury model. Intrathecally delivered antagonists for N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors, but not for the metabotropic glutamate receptors, caused a dose-dependent allodynia reversal in the transgenic mice without changing the behavioral sensitivity in wild-type mice. This suggests that elevated spinal Ca(v)alpha(2)delta(1) mediates allodynia through a pathway involving activation of selective glutamate receptors. To determine if this is mediated by enhanced spinal neuronal excitability or pre-synaptic glutamate release in deep-dorsal horn, we examined wide-dynamic-range (WDR) neuron excitability with extracellular recording and glutamate-mediated excitatory postsynaptic currents with whole-cell patch recording in deep-dorsal horn of the Ca(v)alpha(2)delta(1) transgenic mice. Our data indicated that overexpression of Ca(v)alpha(2)delta(1) in neuronal tissues led to increased frequency, but not amplitude, of miniature excitatory post synaptic currents mediated mainly by AMPA/kainate receptors at physiological membrane potentials, and also by NMDA receptors upon depolarization, without changing the excitability of WDR neurons to high intensity stimulation. Together, these findings support a mechanism of Ca(v)alpha(2)delta(1)-mediated spinal sensitization in which elevated Ca(v)alpha(2)delta(1) causes increased pre-synaptic glutamate release that leads to reduced excitation thresholds of post-synaptic dorsal horn neurons to innocuous stimuli. This spinal sensitization mechanism may mediate at least partially the neuropathic pain states derived from increased pre-synaptic Ca(v)alpha(2)delta(1) expression.