Jet-injection assisted photodynamic therapy for superficial and nodular basal cell carcinoma: A pilot study.

BACKGROUND: Photodynamic therapy (PDT) with topical δ-Aminolevulinic acid (ALA) has efficacy in treating basal cell carcinoma (BCC) but is limited by incomplete penetration of ALA into the deeper dermis. This prospective open-label pilot trial investigated the safety and efficacy of photosensitizer jet injection for PDT (JI-PDT) for BCC treatment. It was performed with 15 patients (n = 15) with histologically confirmed, untreated, low-risk nodular BCCs at a single institution. METHODS: For the intervention, JI-PDT patients (n = 11) received two sessions of jet-injected ALA with PDT separated by four to 6 weeks. To further understand treatment technique, another group of patients (n = 4) received jet-injected ALA followed by tumor excision and fluorescence microscopy (JI-E). Treatment tolerability was assessed by local skin responses (LSR) score at five distinct time intervals. Fluorescence microscopy assessed protoporphyrin IX penetration depth and biodistribution within the tumor. At the primary endpoint, tumor clearance was evaluated via visual inspection, dermoscopy and reflectance confocal microscopy. Postinjection and postillumination pain levels, and patient satisfaction, were scored on a 0-10 scale. RESULTS: Fifteen participants with mean age of 58.3, who were 15/15 White, non-Hispanic enrolled. The median composite LSR score immediately after JI-PDT was 5 (interquartile range [IQR] = 3) which decreased to 0.5 (IQR = 1) at primary endpoint (p < 0.01). Immunofluorescence of excised BCC tumors with jet-injected ALA showed photosensitizer penetration into papillary and reticular dermis. Of the 13 JI-PDT tumors, 11 had tumor clearance confirmed, 1 recurred, and 1 was lost to follow-up. 1/11 patients experienced a serious adverse event of cellulitis. 70% of patients had local scarring at 3 months. Patients reported an average pain level of 5.6 (standard deviation [SD] = 2.3) during jet injection and 3.7 (SD = 1.8) during light illumination. CONCLUSIONS: Jet injection of ALA for PDT treatment of nodular low-risk BCC is tolerable and feasible and may represent a novel modality to improve PDT.

Home-Use Hyaluronic Acid Jet Injectors: Unreliable and Unsafe.

BACKGROUND: Needle-free hyaluronic acid (HA) jet injectors are gaining popularity for rejuvenation treatment. The devices are widely available online and are used for self-injection or in beauty salons by nonphysicians. However, little is known about their performance and safety. OBJECTIVE: To explore the injection efficiency and cutaneous biodistribution patterns administered with home-use compared with medical jet injectors and to assess safety aspects. MATERIALS AND METHODS: The authors injected HA into ex vivo human skin with 4 home-use and 2 medical injectors. The intracutaneous dose of HA was calculated, and the cutaneous biodistribution of HA was assessed using a 3-dimensional Fluorescent Imaging Cryomicrotome System (3D-FICS). Safety aspects were evaluated based on the presence of a manual, CE (conformité européenne) mark, and sterility. RESULTS: The intracutaneous dose delivered by the home-use injectors was markedly lower compared with the medical injectors. 3D imaging for home-use injectors showed superficial epidermal distribution with low distribution volumes. For medical injectors, volumes were substantially larger and mainly middermal. All evaluated safety aspects were lacking. CONCLUSION: Results of this study suggest that the specific combinations of home-use injectors and HA used in this study are unreliable and unsafe, which casts doubts on the performance of these treatments in general.

Delivery of Experimental mRNA Vaccine Encoding the RBD of SARS-CoV-2 by Jet Injection.

We studied a needle-free jet injection delivery of an experimental mRNA vaccine encoding the receptor-binding domain of the SARS-CoV-2 S protein (mRNA-RBD). Immunization of BALB/c mice with mRNA-RBD by a needle-free jet injector induced high levels of antibodies with virus-neutralizing activity and a virus-specific T-cell response. The immune response was low in the group of mice that received intramuscular injection of mRNA-RBD. The effectiveness of this simple and safe method of mRNA delivering has been demonstrated. Thus, jet injection of mRNA vaccine can be a good alternative to lipid nanoparticles.

Needle-free electronically controlled jet injection with corticosteroids in recalcitrant keloid scars: a retrospective study and patient survey.

First-line treatment of keloids consists of intralesional needle injections with corticosteroids, but generally entails multiple painful sessions, resulting in variable clinical outcomes. Novel needle-free jet injectors may facilitate more effective and patient-friendly dermal drug delivery. Here, we evaluated the effectiveness, tolerability and patient satisfaction of intralesional triamcinolone-acetonide (TCA) treatment in recalcitrant keloids using an electronically controlled pneumatic injector (EPI). A retrospective study was conducted in recalcitrant keloid patients with a history of severe pain during needle injections who received three sessions of EPI + TCA. Outcome measures included Patient and Observer Scar Assessment Scale (POSAS), Global Aesthetic Improvement Scale (GAIS), treatment-related pain (NRS), adverse effects, and patient satisfaction (survey). Ten patients with in total 283 keloids were included. The POSAS score significantly improved at follow-up and GAIS was reported as '(very) improved' for all patients. EPI + TCA was well-tolerated with a significantly lower NRS pain score compared to needle + TCA (pilot treatment). Only minor adverse effects occurred, and 90% of patients preferred EPI over needle treatment. EPI + TCA is an effective and tolerable treatment for patients with recalcitrant keloids. The minimal treatment-related pain and high patient satisfaction makes it a promising treatment for patients with needle-phobia and/or severe pain during needle injections.

A Promising Needle-Free Pyro-Drive Jet Injector for Augmentation of Immunity by Intradermal Injection as a Physical Adjuvant.

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.

Needle-free jet injection-induced small-droplet aerosol formation during intralesional bleomycin therapy.

OBJECTIVES: Needle-free jet injectors are frequently used in dermatological practice. Injection-generated small-droplet aerosols could be harmful upon inhalation when chemotherapeutics, like bleomycin, are used. Here, we aim to explore jet injector-induced small-droplet aerosol formation of bleomycin in relation to air ventilation and to provide safety measures for clinical practice. MATERIALS AND METHODS: With a professional particle sensor, we measured airborne aerosol particles (0.2-10.0 µm) after electronic pneumatic injection (EPI), spring-loaded jet injection (SLI), and needle injection (NI) of bleomycin and saline (100 µl) on ex vivo human skin. Three levels of air ventilation were explored: no ventilation, room ventilation, and room ventilation with an additional smoke evacuator. RESULTS: EPI and SLI induced significant small-droplet aerosol formation compared with none after NI (0.2-1.0 µm; no ventilation). The largest bleomycin aerosol generation was observed for the smallest particles (0.2-1.0 µm) with 673.170 (528.802-789.453) aerosol particles/liter air (EPI; no ventilation). Room ventilation and smoke evacuation led to a reduction of ≥99% and 100% of measured aerosols, respectively. CONCLUSION: Jet injectors generate a high number of small-droplet aerosols, potentially introducing harmful effects to patients and healthcare personnel. Room ventilation and smoke evacuation are effective safety measures when chemotherapeutics are used in clinical practice.

Clinical endpoints of needle-free jet injector treatment: An in depth understanding of immediate skin responses.

OBJECTIVES: Needle-free jet injectors have been used in dermatological practice for many years. However, predefined clinical endpoints that guide physicians to choose optimal device settings have not been clearly defined. Here, we evaluate immediate skin responses as clinical endpoints for needle-free jet injector treatments. METHODS: We injected methylene blue in ex vivo human skin using an electronically-controllable pneumatic injector (EPI; 3-6 bar, 50-130 µl; n = 63), and a spring-loaded jet injector (SLI) with fixed settings (100 µl; n = 9). We measured the immediate skin papule (3D-camera), residual surface fluid (pipette), dermal dye distribution by estimating depth and width, and subcutaneous dye deposition. RESULTS: EPI with 4 bar and 100 µl resulted in the largest skin papule of 48.7 mm3 (35.4-62.6 mm3 ) and widest dermal distribution of 8.0 mm (5.5-9.0 mm) compared to EPI with 6 bar and 100 µl (p < 0.001, p = 0.018, respectively). The skin papule volume showed a significant moderate to high positive correlation with the width and depth of dye distribution in the dermis (rs = 0.63, rs = 0.58, respectively; p < 0.001 for both correlations). SLI showed high variability for all outcome measures. Finally, a trend was observed that a small skin papule (≤7 mm) and little residual surface fluid (≤10% of injection volume) were warning signs for subcutaneous deposition. CONCLUSIONS: The immediate skin papule and residual surface fluid correspond with dermal drug deposition and are relevant clinical endpoints for needle-free jet injector treatments in dermatological practice.

A one-time pneumatic jet-injection of 5-fluorouracil and triamcinolone acetonide for treatment of hypertrophic scars-A blinded randomized controlled trial.

BACKGROUND: Patients with hypertrophic scars (HTS) risk reduced quality of life due to itching, pain, poor cosmesis, and restriction of movement. Despite good clinical efficacy, patients are often reluctant to undergo repeated needle injections due to pain or needle phobia. OBJECTIVES: To evaluate the applicability of needle-free pneumatic jet injection (PJI) and assess changes in hypertrophic scars following a single PJI treatment with 5-fluorouracil (5-FU) and triamcinolone acetonide (TAC). METHODS: Twenty patients completed this blinded, randomized, controlled, split-scar trial. The intervention side of the HTS received a one-time treatment with PJIs containing a mixture of TAC + 5-FU injected at 5 mm intervals (mean 7 PJI per HTS); the control side received no treatment. Assessments were made at baseline and 4 weeks posttreatment. Outcome measures included change in (1) Vancouver Scar Scale (VSS) total score and subscores, (2) scar volume and surface area assessed by three-dimensional imaging, (3) skin microarchitecture measured by optical-coherence tomography (OCT), (4) photo-assessed scar cosmesis (0-100), (5) patient-reported pain and satisfaction (0-10), and (6) depiction of drug biodistribution after PJI. RESULTS: PJI with TAC + 5-FU significantly decreased both HTS height (-1 VSS; p = 0.01) and pliability (-1 VSS; p < 0.01) with a nonstatistically significant reduction of -1 in total VSS score (0 in control; p = 0.09). On 3D imaging, a 33% decrease in scar volume (p = 0.016) and a 37% decrease in surface area (p = 0.008) was observed. OCT indicated trends towards smoother scar surface (Ra 11.1-10.3; p = 0.61), normalized dermal microarchitecture (attenuation coefficient: 1.52-1.68; p = 0.44), and a reduction in blood flow between 9% and 17% (p = 0.50-0.79). Despite advances in VSS subscores and OCT, no improved photo-assessed cosmesis was found (-3.2 treatment vs. -1.4 control; p = 0.265). Patient-reported pain was low (2/10) and 90% of the patients that had previously received needle injections preferred PJI to needle injection. Depositions of TAC + FU were imaged reaching deep into the scar at levels corresponding to the reticular dermis. CONCLUSION: A single PJI injection containing 5-FU and TAC can significantly improve the height and pliability of HTS. PJI is favored by the patients and may serve as a complement to conventional needle injections, especially for patients with needle phobia.

The Effect of Lidocaine Delivered by Jet Injection on First Attempt Venous Access Success Rates in the Pediatric Emergency Department.

BACKGROUND: Jet injection of 1% lidocaine (J-Tip) has been used in the pediatric emergency department (PED) to reduce pain associated with venipuncture, but there are limited data on the effect of J-Tip on first-attempt venous access success rates. We sought to determine if using a J-Tip altered the first-attempt venous access success rate in the PED. Then, we examined the effect of J-Tip use on pain scores and resource utilization during peripheral venous access. METHODS: We prospectively evaluated children over 6 months of age who required peripheral venous access in the PED. The exposure group received 0.25 mL of 1% buffered lidocaine via jet injection 90 seconds before peripheral venous access. The control group received no local anesthesia. Parent and nurse surveys were completed during the visit. RESULTS: There was no difference in first attempt success rate between the exposure (n = 136) and control (n = 90) groups (87% vs 88%, P = 0.82). J-Tip use was associated with improved pain scores based on child report (median 1 vs 3; P < 0.001), parent report (median 1 vs 3; P < 0.001), and nurse assessment (median 0 vs 3; P < 0.001). CONCLUSIONS: Use of J-Tip in the PED to reduce pain associated with peripheral venous access did not lead to a reduction in first-attempt success rates for peripheral venous access. J-Tip was well received among nurses and parents and was associated with improved pain scores.

A Comparison in Patient Comfort Using Conventional Syringe and Needleless Jet Anesthesia Technique in Periodontal Surgery-A Split-Mouth Randomized Clinical Trial.

Background and Objectives: Periodontal surgery requires local anesthetic coverage to alleviate patient discomfort. Needles and injections can engender feelings of fear and anxiety in individuals. This study aimed to assess the level of comfort and anxiety in patients during the administration of local anesthesia using needleless jet anesthesia (JA) when compared to a conventional syringe (CS) in periodontal surgery. Method and Materials: 60 sites were designated for injection in a split-mouth design in 30 subjects who required periodontal surgery. Local anesthesia was administered in two appointments scheduled one week apart using either a JA system or a CS. The Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), and Beck's anxiety inventory were used to report the pain and anxiety levels while injecting local anesthesia. Statistical analysis of the results was performed using the Shapiro-Wilks test and Paired t-test. Results: Patients reported greater comfort with JA. The VAS and VRS values were statistically significant-(p = 0.003) and (p = 0.001), respectively. Patients showed fear and were nervous about receiving a local anesthetic using a CS. A few subjects experienced lingering pain with the CS, whereas greater comfort and no lingering soreness were reported post-operatively at the site of JA administration. Conclusions: This study provides the first comprehensive assessment of using JA for periodontal surgical procedures. Lower pain scores were consistently observed with the use of jet injectors. Patients were at ease and reported lesser anxiety and greater comfort with jet injectors, making it ideally suited for providing local anesthesia in periodontal surgery.

Needle-Free Injection Assisted Drug Delivery-Histological Characterization of Cutaneous Deposition.

BACKGROUND AND OBJECTIVES: Many cutaneous drug-delivery techniques rely on passive diffusion to deliver topical compounds to the skin. When attempting to deliver drugs to thicker lesions, such as skin tumors, modalities that do not rely on diffusion may serve as a better drug-delivery method. In this histological study, we aim to investigate the cutaneous delivery patterns of an electronic pneumatic needle-free injection device. STUDY DESIGN/MATERIALS AND METHODS: Needle-free-injection was investigated in 24 ex vivo porcine skin samples and one basal cell carcinoma (BCC) tissue sample. A needle-free injection device with a nozzle size of 200 µm delivered 80 µl compound ink (0.1 cc black ink: 5.0 cc saline) at low (30%/3.1 bar; n = 6 porcine skin; n = 1 BCC tissue), medium (50%/3.9 bar; n = 6 porcine skin), high (65%/4.6 bar; n = 6 porcine skin), and stacked (30 + 50%/3.1 + 3.9 bar; n = 6 porcine skin) pressures. Depth, width, and depth of maximum width of ink deposition were evaluated on histological slides. RESULTS: Depositions with small ink-lined vacuoles were seen intra-dermally in all samples, including the BCC tissue. Deposition depth was similar at low and medium pressures (924 vs. 994 µm; P = 0.873) but increased significantly with high pressure (1,564 µm; P = 0.010). When injections were stacked (3.1 + 3.9 bar), the depth remained similar to that of a single injection (931 µm; P = 1.000). The width of the deposition stayed comparable for low, medium, and high pressures when a single needle-free injection was performed (30% = 2,394 µm; 50% = 2,226 µm; and 65% = 2,757 µm; P = 0.09), but increased significantly with stacking (2,979 µm; P = 0.037). The depth of maximal width was superficially located in the papillary dermis at low and medium pressures (321 and 305 µm; P = 0.748) but shifted to the deeper reticular dermis with high pressure (950 µm; P = 0.004) and with stacking (734 µm; P = 0.004). CONCLUSIONS: In conclusion, with an electronically controlled, pneumatic needle-free injector, depth and width of a cutaneous deposition can be influenced by pressure and stacking, respectively. The pneumatic needle-free injection can potentially serve as a viable drug-delivery technique for cutaneous pathologies where dermal deposition is essential. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Needle-free pneumatic injection device; histologic assessment using a rat model and parameter comparison in predicting collagen synthesis degree.

BACKGROUND: Needle-free pneumatic injections have been recently introduced to the field of dermatology to inject such substances as hyaluronic acid. However, data on the influence of various pneumatic injection parameters on collagen synthesis are lacking. OBJECTIVE: Compare the effect of diameter, pressure, and volume of a pneumatic injection jet on collagen synthesis and fluid dispersion pattern using a rat model. Investigate if the total work force of the injection jet is useful in predicting the degree of collagen synthesis. MATERIALS AND METHODS: We injected fluid with 1 mg/ml of hyaluronic concentration to adult rats. Different injection pressures and volumes were tested using devices with nozzles of different diameters. Collagen synthesis areas were then measured, and statistical analyses were performed. RESULTS: The area of collagen fibers increased for up to two months. The injection pressure and volume did not correlate with the degree of collagen synthesis. The nozzle diameter showed a significant after two and four weeks of injection. The total work force correlated with collagen synthesis 2, 4, and 8 weeks post-injection. (P = 0.043, 0.027, and 0.000, respectively). CONCLUSION: Collagen formation is more prominent 2 months post-hyaluronic acid injection than after 1 month when using a needle-free pneumatic injection device. The total work force, which is affected by both the nozzle diameter and injection pressure, can be helpful in predicting the degree of collagen synthesis. Lasers Surg. Med. 51:278-285, 2019. © 2019 Wiley Periodicals, Inc.

Efficacy and tolerability of the new autoinjected suspension of exenatide once weekly versus exenatide twice daily in patients with type 2 diabetes.

AIMS: To simplify administration of aqueous exenatide once weekly, which requires reconstitution, the exenatide microspheres have been reformulated in a ready-to-use autoinjector with a Miglyol diluent (exenatide QWS-AI). This study compared the efficacy and safety of exenatide QWS-AI with the first-in-class glucagon-like peptide-1 receptor agonist exenatide twice daily (BID). MATERIALS AND METHODS: This randomized, open-label, controlled study in patients with type 2 diabetes using diet and exercise or taking stable oral glucose-lowering medication randomized patients 3:2 to either exenatide QWS-AI (2 mg) or exenatide BID (10 µg) for 28 weeks. The primary outcome was the 28-week change in glycated haemoglobin (HbA1c). A subset of patients completed a standardized meal test for postprandial and pharmacokinetic assessments. RESULTS: A total of 375 patients (mean HbA1c, 8.5% [69 mmol/mol]; body mass index, 33.2 kg/m2 ; diabetes duration, 8.5 years) received either exenatide QWS-AI (n = 229) or exenatide BID (n = 146); HbA1c was reduced by -1.4% and -1.0%, respectively (least-squares mean difference, -0.37%; P = .0072). More patients achieved HbA1c <7.0% with exenatide QWS-AI (49.3%) than with exenatide BID (43.2%; P = .225). Body weight was reduced in both groups (P = .37 for difference). Gastrointestinal adverse events (AEs) were reported in 22.7% (exenatide QWS-AI) and 35.6% (exenatide BID) of patients; fewer patients in the exenatide QWS-AI group withdrew because of AEs than in the exenatide BID group. Minor hypoglycaemia occurred most often with concomitant sulfonylurea use. CONCLUSIONS: Exenatide QWS-AI was associated with a greater reduction in HbA1c, similar weight loss and a favorable gastrointestinal AE profile compared with exenatide BID.

Evaluation of changes in skin biophysical parameters and appearance after pneumatic injections of non-cross-linked hyaluronic acid in the face.

BACKGROUND: Pneumatic injections of non-cross-linked hyaluronic acid are effective in skin rejuvenation, however, the associated biophysical parameters and appearance have not been evaluated. OBJECTIVES: To determine the changes in skin biophysical parameters after facial pneumatic injections of non-cross-linked hyaluronic acid. PATIENTS AND METHODS: Twenty-eight healthy female volunteers received pneumatic injections of non-cross-linked hyaluronic acid into the face for consecutive 5 weeks. Skin biophysical parameter assessment and clinical evaluation were performed using the CK Multi-Probe Adapter and Visia system. Five of the volunteers also underwent retroauricular skin biopsy before and after the last treatment. The skin tissues were all stained with Masson-trichrome, Verhoeff-van Gieson stain, and hematoxylin-eosin to evaluate the changes in collagen, elastic fibers, and the epidermis, before and after the last treatment. RESULTS: Transepidermal water loss was significantly lower in week 4 (18.46 ± 4.70 g/h/m2) than at the baseline (22.03 ± 7.15 g/h/m2, p < 0.05). Skin texture was better in week 4 (599.29 ± 354.32) than at the baseline (668.43 ± 342.55, p < 0.05). Skin pores also improved significantly at week 4 (934.07 ± 458.78) compared to the baseline (1024.57 ± 415.31, p < 0.05). Skin wrinkles were improved at the 3-month follow-up (29.29 ± 11.11) compared to the baseline (35.83 ± 16.05, p < 0.05). CONCLUSION: Pneumatic injections of non-cross-linked hyaluronic acid improved skin TEWL, texture, pores, and wrinkles.

Effect of exercise combined with glucagon-like peptide-1 receptor agonist treatment on cardiac function: A randomized double-blind placebo-controlled clinical trial.

In patients with type 2 diabetes, both supervised exercise and treatment with the glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA) liraglutide may improve cardiac function. We evaluated cardiac function before and after 16 weeks of treatment with the GLP-1RA liraglutide or placebo, combined with supervised exercise, in 33 dysregulated patients with type 2 diabetes on diet and/or metformin. Early diastolic myocardial tissue velocity was improved by exercise in the placebo group (mean ± standard deviation [s.d.] -7.1 ± 1.6 to -7.7 ± 1.8 cm/s, P = .01), but not in the liraglutide group (-7.1 ± 1.4 to -7.0 ± 1.4 cm/s, P = .60; between groups, P = .02). Similarly, the mean ± s.d. ratio of early and atrial mitral annular tissue velocities improved in the placebo group (1.0 ± 0.4 to 1.2 ± 0.4, P = .003), but not in the liraglutide group (1.0 ± 0.3 to 1.0 ± 0.3, P = .87; between groups, P = .03). We found no significant differences in heart rate, left ventricular (LV) structure or function within or between the groups. In conclusion, the addition of liraglutide to exercise in sedentary patients with dysregulated type 2 diabetes may blunt the suggested beneficial effect of exercise on LV diastolic function.

Efficacy and safety of autoinjected exenatide once-weekly suspension versus sitagliptin or placebo with metformin in patients with type 2 diabetes: The DURATION-NEO-2 randomized clinical study.

AIMS: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors treat type 2 diabetes through incretin-signaling pathways. This study compared the efficacy and safety of the glucagon-like peptide-1 receptor agonist exenatide once-weekly (Miglyol) suspension for autoinjection (QWS-AI) with the dipeptidyl peptidase-4 inhibitor sitagliptin or placebo. MATERIALS AND METHODS: In this open-label, multicentre study of patients with type 2 diabetes who had suboptimal glycaemic control on metformin monotherapy, 365 patients were randomized to receive exenatide 2.0 mg QWS-AI, sitagliptin 100 mg once daily or oral placebo (3:2:1 ratio). The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to 28 weeks. RESULTS: At 28 weeks, exenatide QWS-AI significantly reduced HbA1c from baseline compared to sitagliptin (-1.13% vs -0.75% [baseline values, 8.42% and 8.50%, respectively]; P = .02) and placebo (-0.40% [baseline value, 8.50%]; P = .001). More exenatide QWS-AI-treated patients achieved HbA1c <7.0% than did sitagliptin- or placebo-treated patients (43.1% vs 32.0% and 24.6%; both P < .05). Exenatide QWS-AI and sitagliptin reduced fasting plasma glucose from baseline to 28 weeks (-21.3 and -11.3 mg/dL) vs placebo (+9.6 mg/dL), with no significant difference between the 2 active treatments. Body weight decreased with both active treatments (-1.12 and -1.19 kg), but not with placebo (+0.15 kg). No improvement in blood pressure was observed in any group. The most common adverse events with exenatide QWS-AI were gastrointestinal events and injection-site reactions. CONCLUSIONS: This study demonstrated that exenatide QWS-AI reduced HbA1c more than sitagliptin or placebo and was well tolerated.

Transcutaneous pneumatic injection of glucose solution: a morphometric evaluation of in vivo micropig skin and tissue-mimicking phantom.

BACKGROUND: Needle-free, transcutaneous pneumatic injection systems can be used to deliver therapeutic solutions to targeted layers of skin in a minimally invasive manner. METHODS: To evaluate jet infiltration patterns and tissue reactions, 5% isotonic and 20% hypertonic glucose solutions were pneumatically injected into in vivo micropig skin. Gelatin TM phantom was additionally prepared to analyze penetration and dispersion patterns for different experimental settings. RESULTS: As immediate tissue reactions in the in vivo micropig skin, distinct pneumatic injection injury zones (PIIZs) in the dermis, extending from the papillary dermis deep into the dermo-subcutaneous junction, were generated with the 5% and 20% glucose solutions and with pneumatic pressures of 4.64 and 5.7 bars, respectively. PIIZs markedly decreased in appearance at 1 day after treatment, accompanied by inflammatory cell infiltration, and disappeared at 7 days post-treatment with increased collagen and elastin production. In TM phantom study, the PIIZs created by 20% glucose mainly comprised a single, homogenous, round to oval zone, whereas those created by 5% glucose were irregular and multi-lobular. CONCLUSION: The present study suggests that transcutaneous pneumatic injection therapy may exert mechanical stimulatory effects, immediate tissue shrinkage via hypertonic solutions, and late tissue regeneration effects during wound healing.

Treatment of Palmar Hyperhidrosis With Needle Injection Versus Low-Pressure Needle-Free Jet Injection of OnabotulinumtoxinA: An Open-Label Prospective Study.

BACKGROUND: OnabotulinumtoxinA (OnabotA) injections are effective to treat palmar hyperhidrosis (HH) but are quite painful. OBJECTIVE: To evaluate efficacy and pain of OnabotA injection using a needle-free jet apparatus compared with the traditional needle injection to treat palmar HH. METHODS: Twenty patients were recruited for a prospective open-label study. Their right hand was injected with 1% lidocaine with a jet injector, after which OnabotA was injected with a needle. The left hand was injected with OnabotA directly using the jet injector. Pain scores were recorded for both techniques. At 0, 1, 3, and 6 months, severity of palmar HH was evaluated with the Hyperhidrosis Disease Severity Scale (HDSS). RESULTS: One point reduction in the HDSS score at 1 month showed no statistical difference between both hands (p = .451). However, the HDSS score at 1 month from baseline dropped by 1.6 for the hand treated with traditional needle injection of OnabotA compared with 1.25 for the hand treated with jet injections (p = .031). There was no statistical difference in the pain on injection with both techniques (p = .1925). CONCLUSION: This study demonstrates effective and relatively painless use of a low-pressure jet injector for OnabotA in palmar HH.

Pressure- and dose-controlled transcutaneous pneumatic injection of hypertonic glucose solution for the treatment of atrophic skin disorders.

BACKGROUND: Needleless transcutaneous pneumatic injections (TPIs) are a minimally invasive way to deliver the solution into the skin for therapeutic purposes. The suggested action mechanisms of TPI therapy include mechanical stimulation, immediate tissue shrinkage and late wound healing. METHODS: Thirteen Korean patients were treated with TPI for atrophic skin disorders, including acne scars, striae albae, post-furuncle, or carbuncle scars, and horizontal wrinkles with lipoatrophy. At each TPI treatment session, a single pass was made along with the atrophic skin lesions without overlapping. Thereafter, two dermatologists objectively evaluated the clinical improvement in the lesions in the photographs via the global aesthetic improvement scale (GAIS). RESULTS: One month after the final treatment, the overall mean GAIS score was 2.3 ± 0.8. Six of the 13 (46.2%) patients exhibited clinical improvement of grade 3, five (38.5%) patients grade 2 and two (15.4%) patients grade 1. The overall mean subjective satisfaction score with the TPI treatment was 2.3 ± 0.9. Six of the 13 (46.2%) patients achieved subjective satisfaction of grade 3, six (46.2%) patients grade 2 and one (7.7%) patient grade 0. CONCLUSIONS: The present study demonstrated that the TPI treatment is effective and safe for treating atrophic skin disorders of varying causes in Korean patients.