Effect of Intense Pulsed Light versus Intradermal Tranexamic Acid for the Management of Melasma.

OBJECTIVE: To compare the effectiveness of intense pulsed light (IPL) and intradermal tranexamic acid (TXA) in treating melasma. STUDY DESIGN: A cross-sectional analytical study. Place and Duration of the Study: Department of Dermatology, Dow International Medical College, Dow University Hospital, Karachi, Pakistan, from 15th January to 15th July 2023. METHODOLOGY: A total of 62 patients with melasma, aged 20-50 years, were divided into two groups. Group A (32 patients) received IPL (560 nm filter was used) treatment, and Group B (30 patients) received intradermal TXA. Each group underwent four treatment sessions with varying intervals. Melasma area and severity index (MASI) scores were used to compare the effects of treatment. RESULTS: After a 3-month treatment period, both groups showed reduced mMASI scores compared to baseline with a significant initial difference between Group A (8.6 ± 4.2) and Group B (5.4 ± 2.7, p <0.001). However, post-treatment, there was no significant difference in mMASI scores (Group A: 3.8 ± 2.6; Group B: 3.2 ± 2.0, p = 0.29). IPL treatment (Group A) demonstrated a significant reduction in mMASI scores (57.1 ± 19.7) compared to intradermal TXA treatment (Group B, 42.2 ± 18.8, p = 0.0034). CONCLUSION: Both IPL and intradermal TXA treatments effectively reduced melasma, with IPL exhibiting superior results. However, post-treatment outcomes converged, emphasising the need for personalised approaches considering the unique characteristics of South East Asian skin. KEY WORDS: Intense pulsed light, Melasma, Intradermal tranexamic acid.

Safety and Efficacy of the Modified Vaccinia Ankara-Bavaria Nordic Vaccine Against Mpox in the Real World: Systematic Review and Meta-Analysis.

In May 2022, mpox began to spread worldwide, posing a serious threat to human public health. Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) is a live attenuated orthopoxvirus vaccine that has been authorized by the U.S. Food and Drug Administration as the vaccine of choice for the prevention of mpox. In this study, we conducted a meta-analysis of all currently published literature on the efficacy and safety of the MVA-BN vaccine in the real world, showing that the MVA-BN vaccine is effective and safe, with efficacy of up to 75% with a single dose and up to 80% with a two-dose vaccine. Meanwhile, we found that subcutaneous injection has lower local and systemic adverse events than intradermal injection, regardless of single- or two-dose vaccination, and subcutaneous injection is better tolerated in children, the elderly, or people with underlying medical conditions. These results have important reference value for clinical practice.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Botulinum toxin and hyperhidrosis of the amputation stump in war amputees.

INTRODUCTION: Stump hyperhidrosis is a common condition after lower limb amputation. It affects the prosthesis use, and the quality of life of patients. Several case reports tried to prove benefit of using Botulinum toxin in its treatment. AIM: This study was to conduct a larger workforce clinical trial and to demonstrate benefits of botulinum toxin injection in the treatment of stump hyperhidrosis. METHODS: A prospective study was conducted. War amputees who complained of annoying excessive sweating of the stump were included. They received intradermal injection of botulinum toxin A in the residual limb area in contact with prosthetic socket. Abundance of sweating and degree of functional discomfort associated with it were assessed before, after 3 weeks, 6 and 12 months. RESULTS: Seventeen male patients, followed for post-traumatic limb amputation were included in the study. Discomfort and bothersome in relation to Hyperhidrosis did decrease after treatment (p<0,001). Reported satisfaction after 3 weeks was 73,33%. Improvement of prothesis loosening up after 3 weeks was 72,5% [±15,6]. Mean injection-induced pain on the visual analogue scale was 5.17/10 (±1.58). The mean interval after the onset of improvement was 5.13 days [min:3, max:8]. The mean time of improvement was 10.4 months after the injection [min:6, max:12]. No major adverse events were reported following treatment. CONCLUSION: Intradermal injections of botulinum toxin in the symptomatic treatment of stump hyperhidrosis are effective and have few adverse effects. It improves the quality of life of our patients thanks to a better tolerance of the prosthesis.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Simple Yet Effective-Sterile Water Injections to Treat Labor Pain in the Transport Environment.

Sterile water injections (SWI) is a nonpharmacologic pain relief option to treat back pain in labor. This case report describes and discusses the use of SWI in the context of an obstetric retrieval of a 29-year-old woman who was transferred by the Royal Flying Doctor Service South Eastern Section. It provides an overview of SWI, discusses the relevance for medical transport, and offers suggestions for medical transport professionals.

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

Hyaluronic acid (HA) is a remarkably multifaceted biomacromolecule, playing a role in regulating myriad biological processes such as wound healing, tissue regeneration, anti-inflammation, and immunomodulation. Crosslinked high- and low-molecular-weight hyaluronic acid hydrogels achieve higher molar concentrations, display slower degradation, and allow optimal tissue product diffusion, while harnessing the synergistic contribution of different-molecular-weight hyaluronans. A recent innovation in the world of hyaluronic acid synthesis is represented by NAHYCO® Hybrid Technology, a thermal process leading to hybrid cooperative hyaluronic acid complexes (HCC). This review summarizes the current literature on the in vitro studies and in vivo applications of HCC, from facial and body rejuvenation to future perspectives in skin wound healing, dermatology, and genitourinary pathologies.

A Hollow Microneedle Equipped with a Micropillar for Improved Needle Insertion and Injection of Drug Solution.

PURPOSE: Hollow-type microneedles (hMNs) are a promising device for the effective administration of drugs into intradermal sites. Complete insertion of the needle into the skin and administration of the drug solution without leakage must be achieved to obtain bioavailability or a constant effect. In the present study, several types of hMN with or without a rounded blunt tip micropillar, which suppresses skin deformation, around a hollow needle, and the effect on successful needle insertion and administration of a drug solution was investigated. Six different types of hMNs with needle lengths of 1000, 1300, and 1500 µm with or without a micropillar were used. METHODS: Needle insertion and the disposition of a drug in rat skin were investigated. In addition, the displacement-force profile during application of hMNs was also investigated using a texture analyzer with an artificial membrane to examine needle factors affecting successful insertion and administration of a drug solution by comparing with in vivo results. RESULTS: According to the results with the drug distribution of iodine, hMN1300 with a micropillar was able to successfully inject drug solution into an intradermal site with a high success rate. In addition, the results of displacement-force profiles with an artificial membrane showed that a micropillar can be effective for depth control of the injected solution as well as the prevention of contact between the hMN pedestal and the deformed membrane. CONCLUSION: In the present study, hMN1300S showed effective solution delivery into an intradermal site. In particular, a micropillar can be effective for depth control of the injected solution as well as preventing contact between the hMN pedestal and the deformed membrane. The obtained results will help in the design and development of hMNs that ensure successful injection of an administered drug.

Skin necrosis after intradermal injection of lyophilized exosome: A case report and a review of the literature.

BACKGROUND: Exosomes have gained attention for their potential in skin rejuvenation. Currently, most exosome products are available for topical administration, and the use of subdermal injection as a route of administration has not been approved. AIMS: The purpose of this case report is to describe a case of skin necrosis that occurred following an intradermal injection of lyophilized exosomes. MATERIALS AND METHODS: We hereby report a case of a middle-aged man who experienced adverse effects after receiving an intradermal injection of lyophilized exosomes. Multiple injections of an exosome product were administered to treat enlarged facial pores. Shortly after the injection, the patient felt pain and noticed several dark red bumps. Three days after injection, the lesions transformed into palpable, painful, non-blanchable purplish papules and nodules, accompanied by central, tiny crusted erosions. The residual product was injected into the upper arm using an intradermal method. Similar lesions also appeared, and a skin biopsy showed necrotic keratinocytes, leukocytoclastic vasculitis, and eccrine necrosis. RESULTS: There are few reports available regarding complications, especially those related to intradermal exosomes. These complications include multiple foreign-body granulomatous reactions at the injection sites. In our case, oral prednisolone was administered for a duration of 7 days. After the treatment, the lesions exhibited notable improvement, eventually leaving post-inflammatory hyperpigmentation. CONCLUSION: Utilizing exosomes through unapproved methods should be avoided due to the possibility of adverse reactions that could cause aesthetic issues.

Longitudinal Assessment of Facial Hyperhidrosis Management: Evaluating the Utility and Quality of Life Improvements following Botulinum Toxin Injection.

Facial hyperhidrosis is a debilitating condition that can severely impact the quality of life. This study aimed to assess the long-term utility of Botulinum toxin type A therapy (BTA) for facial hyperhidrosis and its impact on quality of life over a one-year period. Conducted at the Pius Brinzeu Clinical Emergency Hospital in Timisoara, Romania, this longitudinal observational study involved 77 adult patients with primary facial hyperhidrosis. Participants received two sessions of Botulinum toxin injections (50 U IncoBTX-A each) and were evaluated at baseline, 6 months, and 12 months using the Hyperhidrosis Disease Severity Scale (HDSS), WHOQOL-BREF, Dermatology Life Quality Index (DLQI), and a bespoke survey. The study demonstrated significant reductions in HDSS scores from 3.6 ± 0.5 to 1.2 ± 0.8 post-treatment, sustained at 1.3 ± 0.6 at 12 months (p-value < 0.001). DLQI scores markedly decreased from 24.8 ± 4.2 to 6.2 ± 2.1 post-treatment, stabilizing at 6.5 ± 2.5 at 12 months (p-value < 0.001). Sweat production significantly dropped from 0.75 g ± 0.15 to 0.18 g ± 0.07 per 15 min (p-value < 0.001). WHOQOL-BREF scores improved notably in the mental domain from 66.7 ± 6.1 to 70.8 ± 5.2 at 12 months (p-value < 0.001), with physical and social domains also showing significant improvements. Correlation analysis revealed strong negative correlations between DLQI total score and HDSS (rho = -0.72, p-value < 0.001) and sweat production (rho = -0.68, p-value < 0.001). Regression analysis indicated significant predictors for DLQI total score, including HDSS (B Coefficient = -3.8, p-value < 0.001) and sweat production (B Coefficient = -2.2, p-value < 0.001). BTA therapy significantly improved the quality of life in facial hyperhidrosis patients, with lasting effects on symptom severity, sweat production, and quality of life domains. The correlation and regression analyses further substantiated the treatment's impact on both physical and psychological aspects. These findings advocate Botulinum toxin as a viable long-term treatment for facial hyperhidrosis.

Egg microneedles for transdermal vaccination of inactivated influenza virus.

The use of dissolving microneedles (DMNs) is a drug delivery technique in which drug dissolution occurs once it is administered into the skin. The skin is a remarkable site for vaccination due to its significant immunologic properties. Compared to the traditional hypodermic intramuscular (IM) injection, vaccination via DMN does not require cold chains and allows for minimal invasive drug delivery. On account of the significance of skin vaccination, preceding studies have been conducted to elucidate the importance of the DMN technology in vaccination. Most of these studies focused on formulations that maintain the activity of the vaccine, so formulations designed to be specific to the mechanical properties of the microneedle could not be used together independently. In this study, we have developed influenza vaccine loaded egg microneedles (EMN) and characterized the specificity of layer-specific functions of EMN by distinguishing between formulations that can maintain the activity of the vaccine and have the mechanical strength. By the use of in vitro tests such as ELISA and SRID assays, we quantitively evaluated the antigen activity of the formulation candidates to be 87% and 91%, respectively. In vivo tests were also conducted as mouse groups were inoculated with the formulation constructed into egg microneedles (FLU-EMN) to determine the protective efficacy against infection. The results demonstrated that FLU-EMN with functionalized formulations successfully enabled protective immune response even with a fractional dose compared to IM injection.

Management of primary plantar hyperhidrosis with botulinum toxin type A: A retrospective case series of 129 patients.

BACKGROUND/OBJECTIVES: To date, scientific data on the efficacy of botulinum toxin type A (BoNT-A) for primary plantar hyperhidrosis (PPH) are mainly derived from case reports and small case series. Herein, we sought to assess the efficacy and safety of BoNT-A for PPH on a large series of patients. METHODS: Medical records of patients who were referred to the outpatient department for hyperhidrosis of a tertiary care hospital and received BoNT-A for PPH from March 2003 until December 2022 were reviewed. RESULTS: A total of 129 patients [12 males, 117 females; median age 32 years (range, 16-72)] were included in the study, after excluding 24 patients with insufficient documented follow-up data. Most patients [115 (89.1%)] received onabotulinumtoxin-A, nine (7.0%) abobotulinumtoxin-A and five (3.9%) both in subsequent sessions. The mean number of sessions was 2.02 [standard deviation (SD), 2.29] and the mean duration of response 6.16 months (SD, 4.01). The percentage of response, as evaluated by Minor's test, was 71.67%, 63.44%, 47.78% and 34.13% after 1, 3, 6 and 9 months, respectively. Most patients were satisfied (21.7%) or very satisfied (58.9%) with the treatment. No serious side effects were reported. CONCLUSIONS: The results of this retrospective study suggest that BoNT-A is an effective and safe treatment option for PPH.

Toward facial rejuvenation; A clinical trial to assess the efficacy of nano fat grafting on wrinkles.

INTRODUCTION: With increasing age, patients' facial volume decrease. For this reason, nano fat grafting has recently gained popularity as adjunctive treatment to facial rejuvenation procedures. However, few quantitative studies have been conducted to investigate the impact of nano fat on facial wrinkles. AIMS: In the present study, authors aim to investigate the therapeutic effect of intradermal injection of nano fat on fine facial wrinkles and assess their changes over 7 months of follow-up. METHODS: In this randomized trial, 15 patients with fine facial wrinkles were enrolled. The fat was harvested from the abdomen and processed into nano fat. Nano fat was injected into the facial wrinkles intradermally with a needle of 27 gauge. The patients were evaluated before and 7 months postinjection utilizing Visio face 1000D (CK electronic, manufactured in Germany); and four parameters of wrinkles (area, volume, depth, and percent area) were evaluated before and after the nano fat injection. RESULTS: Our evaluation with Visio face showed that nano fat injection was significantly reduced the volume, area, depth, and percent area of wrinkles after 7 months of follow-up without serious long-lasting adverse effects. Moreover, wrinkles with higher percent area, depth and volume loss show greater improvement after the treatment. Our results also indicate that males and females equally benefit from this treatment except for the percent area parameter that was improved more significantly in male patients. CONCLUSION: Our study showed that intradermal injection of nano fat significantly decreases the volume, area, depth, and percent area of fine facial wrinkles. Further quantitative studies with control groups and larger sample sizes are required.

Boostability after single-visit pre-exposure prophylaxis with rabies vaccine: a randomised controlled non-inferiority trial.

BACKGROUND: After rabies pre-exposure prophylaxis (PrEP) vaccination, scarcely available rabies immunoglobulins are not required for post-exposure prophylaxis (PEP). However, PrEP is not sufficiently accessible as it is cost-intensive and time-intensive. This study investigates whether rabies PrEP schedules can be shortened to one visit, removing some of these barriers. METHODS: In a block-randomised (2:2:2:1) controlled, multicentre non-inferiority trial, healthy adult travellers (aged 18-50 years and >50 years) were randomly assigned to (A) single-visit intramuscular (1·0 mL); (B) single-visit intradermal (0·2 mL); (C) standard two-visit intramuscular (1·0 mL; day 0 and 7) PrEP; or (D) no rabies vaccination. 6 months later, participants received simulated intramuscular rabies PEP (1·0 mL; day 0 and 3). Rabies virus neutralising antibody (RVNA) concentrations were measured repeatedly. The primary outcome was the fold increase in geometric mean RVNA concentrations between day 0 and 7 after simulated PEP for all participants. The two main comparisons of this primary outcome are between the standard two-visit schedule and the one-visit intramuscular schedule, and between the standard two-visit schedule and the one-visit intradermal schedule. The non-inferiority margin was 0·67. This study is registered with EudraCT, 2017-000089-31. FINDINGS: Between May 16, 2018, and March 26, 2020, 288 healthy adult travellers were randomly assigned and 214 participants were evaluated for the primary outcome. Single-visit intramuscular rabies PrEP induced an anamnestic antibody response non-inferior compared with the two-visit intramuscular schedule; single-visit intradermal PrEP did not. The fold increases in the single-visit intramuscular and the single-visit intradermal schedule were 2·32 (95% CI [1·43-3·77]) and 1·11 (0·66-1·87) times as high as the fold increase in the standard schedule, respectively. No vaccine-related serious adverse events were observed. Adverse events related to vaccination were mostly mild. INTERPRETATION: Single intramuscular rabies vaccination can effectively prime travellers (aged 18-50 years), and potentially other populations, and could replace current standard two-visit rabies vaccination as PrEP. FUNDING: ZonMW. TRANSLATION: For the Dutch translation of the abstract see Supplementary Materials section.

Single-cell RNAseq identifies clonally expanded antigen-specific T-cells following intradermal injection of gold nanoparticles loaded with diabetes autoantigen in humans.

Gold nanoparticles (GNPs) have been used in the development of novel therapies as a way of delivery of both stimulatory and tolerogenic peptide cargoes. Here we report that intradermal injection of GNPs loaded with the proinsulin peptide C19-A3, in patients with type 1 diabetes, results in recruitment and retention of immune cells in the skin. These include large numbers of clonally expanded T-cells sharing the same paired T-cell receptors (TCRs) with activated phenotypes, half of which, when the TCRs were re-expressed in a cell-based system, were confirmed to be specific for either GNP or proinsulin. All the identified gold-specific clones were CD8+, whilst proinsulin-specific clones were both CD8+ and CD4+. Proinsulin-specific CD8+ clones had a distinctive cytotoxic phenotype with overexpression of granulysin (GNLY) and KIR receptors. Clonally expanded antigen-specific T cells remained in situ for months to years, with a spectrum of tissue resident memory and effector memory phenotypes. As the T-cell response is divided between targeting the gold core and the antigenic cargo, this offers a route to improving resident memory T-cells formation in response to vaccines. In addition, our scRNAseq data indicate that focusing on clonally expanded skin infiltrating T-cells recruited to intradermally injected antigen is a highly efficient method to enrich and identify antigen-specific cells. This approach has the potential to be used to monitor the intradermal delivery of antigens and nanoparticles for immune modulation in humans.

Observation on cadavers and through ultrasonography using a 2 mm needle length for intradermal injections.

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.

Antigen-loaded flagellate bacteria for enhanced adaptive immune response by intradermal injection.

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.

Case Report: Survival from Clinical Rabies in a Young Child from Maharashtra, India, 2022.

A 3.5-year-old male child from Maharashtra, India, presented with features of meningoencephalitis approximately 1 month after sustaining severe bite injuries on the right hand from a stray dog. He had received four doses of post-exposure intradermal rabies vaccination (on days 0, 3, and 7 of the bite and erroneously on day 20, instead of day 28 as recommended in the updated Thai Red Cross regimen) as well as local and systemic injections of equine rabies immune globulin. The child was initially diagnosed with and treated for acute encephalitis syndrome before rabies encephalitis was confirmed by detection of rabies virus neutralizing antibodies in the cerebrospinal fluid. During the emergent period, he also received the antimalarial drug artesunate, recently reported to have antiviral effects against rabies virus. With intensive and supportive care, the child showed substantial clinical improvement over the next few weeks. He has now survived for more than 10 months after disease onset, albeit with severe neurological sequelae including diffuse cerebral and cerebellar atrophy.