Formulation and in vitro characterization of nanoemulsions containing remdesivir or licorice extract: A potential subcutaneous injection for coronavirus treatment.

The management of coronavirus necessitates that medicines are available, reasonably priced, and easy to administer. The work aimed at formulating and characterizing remdesivir and licorice extract nanoemulsions and comparing their efficacy against coronavirus for further subcutaneous injection. First, the solubility of remdesivir was determined in different oils, surfactants, and co-surfactants to choose the optimal nanoemulsion components. Nanoemulsions were optimized concerning surfactant: co-surfactant ratio (5:1, 4:1, 3:1, 2:1, and 1:1) and oil to surfactant: co-surfactant ratio (1:9, 1:8, 1:7, 1:6, 1:5, 1:4, 1:3, 1:2, and 1:1). The formulations were evaluated concerning % transmittance, emulsification time, pH, viscosity, droplet size, polydispersity index, zeta potential, drug content, transmission electron microscopy, in-vitro drug release, stability (of the optimal formulas), and antiviral effect against coronavirus. The optimal nanoemulsion formula was F7, exhibiting an acceptable pH level, a rapid emulsification rate, a viscosity of 20 cP, and 100% drug content. The formulation droplet size was 16 and 17 nm, the polydispersity index was 0.18 and 0.26, and the zeta potential was - 6.29 and - 10.34 mV for licorice extract and remdesivir nanoemulsions, respectively. However, licorice extract nanoemulsion exhibited better release and physical stability. Licorice extract nanoemulsion may be a potential subcutaneous injection for combating mild to moderate coronavirus.

The Art of Dosing for Subcutaneous Immunotherapy in North America.

Subcutaneous immunotherapy (SCIT) is a long-established treatment option for allergic rhinoconjunctivitis. Proper dosing of the allergens is critical for the efficacy and safety of SCIT. Of the hundreds of liquid allergen extracts in the United States, effective and well-tolerated SCIT dosing has only been established for a small number. Thus, SCIT dosing remains largely empiric and continues to be, by necessity, an art. To highlight the complexity of SCIT dosing, this review summarizes the historical and current landscape of U.S. allergen extracts, differences among U.S. and European allergen extracts, allergen selection for SCIT, considerations for compounding of allergen extract mixtures, and recommended dosing. As of 2021, 18 standardized allergen extracts are available in the United States; all other extracts remain unstandardized without characterization of allergen content or potency. U.S. allergen extracts differ from European extracts in formulation and potency characterization. There is no standardized methodology for SCIT allergen selection, and interpretation of allergen sensitization is not straightforward. Compounding of SCIT mixtures requires consideration of potential dilution effects, allergen cross-reactivity, proteolytic activity, and additives. Probable effective dose ranges for SCIT are recommended in U.S. allergy immunotherapy practice parameters, although there are few studies using U.S. extracts supporting these doses as therapeutic. In contrast, optimized doses of sublingual immunotherapy tablets have been confirmed in North American phase 3 trials. The SCIT dosing for each patient remains an art that requires clinical experience and consideration of polysensitization, tolerability, compounding of allergen extract mixtures, and the range of recommended doses within the context of extract potency variability.

Characteristics of adverse reactions due to subcutaneous allergen immunotherapy applied between 2011-2021: Single center experience.

Introduction: The aim of this study was to elucidate the incidence of local, large local and systemic reactions after subcutaneus immunotherapy (SCIT) injections in our clinic and to determine the characteristic features of these adverse reactions. Materials and Methods: A total of 6000 SCIT injections administered to 163 patients between January 2011 and December 2021 were retrospectively evaluated. The study population consisted of patients with allergic rhinoconjunctivitis who underwent SCIT due to pollen, house dust mite or cat allergy, or patients who underwent SCIT due to venom allergy. Demographic characteristics of the patients, diagnoses, allergen sensitivities, immunotherapy protocol applied, adverse reactions, and the characteristics of these reactions were recorded. Result: Totally, 163 patients with a mean age of 36.8 ± 12.7 years were enrolled in this research. Sex distribution was as follows: 55.2% (n= 90) were females. During the study, 218 allergic reactions were detected in 83 patients. The incidence of adverse reactions per injection was 3.6%. The probability of developing an adverse reaction in a patient during the entire subcutaneous immunotherapy was 53.9%. Of the adverse reactions that developed, 94 (43.1%, n= 47) were observed locally while 56 (25.7%, n= 40) were large local reactions, and 68 (31.2%, n= 30) were systemic. Incidence of adverse reactions per injection were 1.5%, 0.9%, and 1.1% for local reaction, large local reaction, and systemic reaction, respectively. Conclusions: The results of this analysis elaborated that subcutaneous immunotherapy is a safe and tolerable treatment modality. However, before initiating treatment, the benefits and risks should be evaluated. The risk of systemic reactions is quite low, but fatal anaphylaxis can occur, so physicians need to be aware of the potential risks.

Comparison of sedation with dexmedetomidine/atipamezole administered subcutaneously at GV20 acupuncture point with usual routes of administration in dogs presented for orthopaedic radiographs.

OBJECTIVES: To evaluate the efficacy of subcutaneous administration of dexmedetomidine/atipamezole at the Governing Vessel 20 (GV20) acupuncture point compared with other administration routes (intramuscular and intravenous) in dogs presented for orthopaedic radiographs. MATERIALS AND METHODS: Prospective, randomised, blinded, controlled clinical study. Sixty-four client-owned dogs were randomly injected with 200 µg/m2 of dexmedetomidine intramuscular (lumbar muscles) (n=20), intravenous (n=23) or subcutaneous at the GV20 point (n=21). Following radiographs, dogs received 2000 µg/m2 of atipamezole intramuscular (n=31), or subcutaneous at the GV20 point (n=27). Degree and time to sedation and recovery were assessed using a sedation scale and a Dynamic and Interactive Visual Analog Scale (DIVAS). Clinical physiological variables and adverse events were used. Statistical linear mixed-effect models (analysis of variance) and Cox models were performed. Significance was set at P-value <0.05. RESULTS: Sedation was insufficient to perform orthopaedic radiographs in six dogs in the intramuscular group. The time to sedation was significantly longer, and sedation scale and DIVAS scores were significantly lower in the intramuscular group. The intravenous group had significantly higher sedation scale and DIVAS scores than the GV20 group. No significant differences were observed between the intramuscular and GV20 recovery groups, although the time effect was significantly more pronounced in the GV20 recovery group. CLINICAL SIGNIFICANCE: Subcutaneous administration of dexmedetomidine and atipamezole at GV20 provided effective sedation and recovery in dogs undergoing orthopaedic radiographic studies. GV20 administration provided a clinically similar level of sedation to the intravenous route, and greater and faster sedation and similar recovery to intramuscular.

Short-Term Effect of Continuous Subcutaneous Insulin Infusion and Multiple Daily Injection in Perioperative Patients with Type 2 Diabetes Mellitus.

Background: Hyperglycemia is common and difficult to control in perioperative patients with type 2 diabetes mellitus (T2DM), which impacts their prognosis after operation. Our study investigated the short-term effect of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in perioperative T2DM patients using the data envelopment analysis (DEA). Methods: T2DM patients (n = 639) who underwent surgeries in Guangdong Provincial Hospital of Traditional Chinese Medicine (2009.01-2017.12) were included. Insulin was provided to each patient during the study and separated into a CSII group (n = 369) and an MDI group (n = 270). DEA was performed to compare the therapeutic indexes and investigate the short-term effect of the CSII group and MDI group. Results: Scale efficiencies of the CSII group with CCR model and BCC model were better than that of the MDI group. Regarding slack variables, with higher surgical levels, the CSII group was closer to the ideal state than the MDI group, which indicated in improving the average fasting blood glucose (AFBG), antibiotic use days (AUD), preoperative blood glucose control time (PBGCT), first postoperative day fasting blood glucose (FPDFBG), and postoperative hospitalization days (PHD). Conclusion: CSII could effectively control blood glucose levels and shorten perioperative hospitalizing time for T2DM patients, indicating that CSII was beneficial in perioperative period and should be promoted clinically.

Nasal and blood transcriptomic pathways underpinning the clinical response to grass pollen immunotherapy.

BACKGROUND: Allergen immunotherapy (AIT) is a well-established disease-modifying therapy for allergic rhinitis, yet the fundamental mechanisms underlying its clinical effect remain inadequately understood. Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy was a randomized, double-blind, placebo-controlled trial of individuals allergic to timothy grass who received 2 years of placebo (n = 30), subcutaneous immunotherapy (SCIT) (n = 27), or sublingual immunotherapy (SLIT) (n = 27) and were then followed for 1 additional year. OBJECTIVE: We used yearly biospecimens from the Gauging Response in Allergic Rhinitis to Sublingual and Subcutaneous Immunotherapy study to identify molecular mechanisms of response. METHODS: We used longitudinal transcriptomic profiling of nasal brush and PBMC samples after allergen provocation to uncover airway and systemic expression pathways mediating responsiveness to AIT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01335139, EudraCT Number: 2010-023536-16. RESULTS: SCIT and SLIT demonstrated similar changes in gene module expression over time. In nasal samples, alterations included downregulation of pathways of mucus hypersecretion, leukocyte migration/activation, and endoplasmic reticulum stress (log2 fold changes -0.133 to -0.640, false discovery rates [FDRs] <0.05). We observed upregulation of modules related to epithelial development, junction formation, and lipid metabolism (log2 fold changes 0.104 to 0.393, FDRs <0.05). In PBMCs, modules related to cellular stress response and type 2 cytokine signaling were reduced by immunotherapy (log2 fold changes -0.611 to -0.828, FDRs <0.05). Expression of these modules was also significantly associated with both Total Nasal Symptom Score and peak nasal inspiratory flow, indicating important links between treatment, module expression, and allergen response. CONCLUSIONS: Our results identify specific molecular responses of the nasal airway impacting barrier function, leukocyte migration activation, and mucus secretion that are affected by both SCIT and SLIT, offering potential targets to guide novel strategies for AIT.

Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction.

BACKGROUND: Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. OBJECTIVES: The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction. METHODS: Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment. RESULTS: The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs). CONCLUSIONS: A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.

Continuous subcutaneous rhPTH infusion for managing difficult chronic hypoparathyroidism. A systematic review.

PURPOSE: Standard treatment for chronic hypoparathyroidism is represented by long-life per os supplementation of calcium and vitamin D. Since 90s, exogenous PTH is also available, but a not negligible number of patients experience a poor control. Starting from the experience with pumps in diabetes, it has been hypothesized that the infusion of PTH through pump might result in a better disease control. The aim of this systematic review is to summarize the published data about continuous subcutaneous PTH infusion in chronic hypoPTH patients and achieve conclusions for clinical practice. METHODS: A comprehensive computer literature search of the PubMed/MEDLINE, Embase, and Scopus databases was conducted by two authors independently (last search on November 30, 2022). All findings were summarized and critically discussed. RESULTS: We included 14 of the 103 retrieved articles, 2 RCTs, 8 case reports, and 4 case series, published between 2008 and 2022. Of the total 40 patients, 17 were adults, and 23 pediatric. The etiology was postsurgical in 50% of cases and genetic in the other 50%. All had a failure of standard care and a rapid improvement of clinical and biochemical parameters on PTH pump therapy, without severe adverse events. CONCLUSIONS: Based on literature, pump PTH infusion may represent an effective, safe, and feasible option for patients with chronic hypoparathyroidism refractory to standard therapy. From a clinical perspective, careful patient selection, a skilled healthcare team, the assessment of the local setting and the collaboration with pump suppliers are essential.

Real-Life Experience of Tralokinumab for the Treatment of Adult Patients with Severe Atopic Dermatitis: A Multicentric Prospective Study.

BACKGROUND: Tralokinumab, the first fully human monoclonal antibody that binds specifically to interleukin-13, was safe and effective for treating atopic dermatitis (AD) in clinical trials, but real-life experience is still limited. OBJECTIVES: The objective of this study was to evaluate the effectiveness and safety of tralokinumab in severe AD in a real-life multicenter prospective cohort. METHODS: Adult patients with severe AD were enrolled between January 2022 and July 2022 and received tralokinumab subcutaneously for 16 weeks. Objective and subjective scores were collected at baseline, weeks 6 and 16. Adverse events were reported throughout the study. RESULTS: Twenty-one patients were included. An improvement of at least 75% on the Eczema Area and Severity Index (EASI 75) was achieved in 66.7% of patients at week 16. The median objective and subjective scores at week 16 were significantly (p < 0.001) lower than those at baseline. Combination with cyclosporine was sometimes necessary at the beginning of treatment, and addition of upadacitinib was required for some patients with very severe disease during the treatment. The most frequent adverse events were flares of eczema (23.8%) and reactions at injection site (19.0%). No cases of conjunctivitis were reported. Four patients (19.0%) discontinued treatment. CONCLUSIONS: Tralokinumab is an effective first-line biotherapy for severe AD. However, therapeutic response may be progressive. Safety data were reassuring. Atopic dermatitis flares or reactions at the injection site may lead to discontinuation of treatment. A history of conjunctivitis on dupilumab is not a contraindication to the initiation of tralokinumab.

Congenital malformations among offspring of women with type 1 diabetes who use insulin pumps: a prospective cohort study.

AIMS/HYPOTHESIS: Continuous subcutaneous insulin infusion by insulin pump is often superior in improving glycaemic control compared with conventional multiple daily insulin injection (MDI). However, whether pump treatment leads to improved pregnancy outcomes in terms of congenital malformations and perinatal death remains unknown. The present aim was to evaluate the risk of malformations and perinatal and neonatal death in pregnant women with type 1 diabetes treated with pump or MDI. METHODS: We performed a secondary analysis of a prospective multinational cohort of 2088 pregnant women with type 1 diabetes in a real-world setting who were treated by pump (n=750) or MDI (n=1338). ORs for offspring with congenital malformations or perinatal or neonatal death were calculated using crude data and by logistic regression on propensity score-matched data. RESULTS: At enrolment (gestational week 8; 95% CI 4, 14), pump users had a higher educational level (university degree: 37.3% vs 25.1%; p<0.001) and better glycaemic control (mean HbA1c: 51±10 mmol/mol [6.8±0.9%] vs 54±14 mmol/mol [7.1±1.3%], p<0.001) compared with MDI users. Moreover, a greater proportion of pump users had an HbA1c level below 75 mmol/mol (9%) (97.6% vs 91.9%, p<0.001), and more often reported taking folic acid supplementation (86.3% vs 74.8%; p<0.001) compared with MDI users. All clinically important potential confounders were balanced after propensity score matching, and HbA1c remained lower in pump users. The proportion of fetuses with at least one malformation was 13.5% in pump users vs 11.2% in MDI users (crude OR 1.23; 95% CI 0.94, 1.61; p=0.13; propensity score-matched (adjusted) OR 1.11; 95% CI 0.81, 1.52; p=0.52). The proportion of fetuses with at least one major malformation was 2.8% in pump users vs 3.1% in MDI users (crude OR 0.89; 95% CI 0.52, 1.51; p=0.66; adjusted OR 0.78; 95% CI 0.42, 1.45; p=0.43), and the proportions of fetuses carrying one or more minor malformations (but no major malformations) were 10.7% vs 8.1% (crude OR 1.36; 95% CI 1.00, 1.84; p=0.05; adjusted OR 1.23; 95% CI 0.87, 1.75; p=0.25). The proportions of perinatal and neonatal death were 1.6% vs 1.3% (crude OR 1.23; 95% CI 0.57, 2.67; p=0.59; adjusted OR 2.02; 95% CI 0.69, 5.93; p=0.20) and 0.3% vs 0.3% (n=2 vs n=4, p=not applicable), respectively. CONCLUSIONS/INTERPRETATIONS: Insulin pump treatment was not associated with a lower risk of congenital malformations, despite better glycaemic control in early pregnancy compared with MDI. Further studies exploring the efficacy and safety of pump treatment during pregnancy are needed.

Comparison of the effectiveness of local anesthesia for the digital block between single-volar subcutaneous and double-dorsal finger injections: a systematic review and meta-analysis of randomized control trials.

Local anesthesia is an effective method to perform digital nerve blocks. In this study, we compare the effectiveness of single-volar subcutaneous and double-dorsal injection through a systematic review and meta-analysis of randomized controlled trials (RCTs). A systematic search of PubMed, Embase, and the Cochrane Library from inception to 7 April 2021 was performed. RCTs with the effects of single-volar subcutaneous and double-dorsal injection were eligible. Meta-analysis was performed using random effect models with pooled standardized mean differences (SMDs) and 95% confidence intervals (CI). RoB 2.0 and GRADE of Recommendation Assessment, Development, and Evaluation criteria were applied for evaluating the bias. A total of 2484 studies were initially identified, with 11 eligible RCTs finally included in the meta-analysis (1363 patients). The pooled data of nine studies showed single-volar injection had a statistically significantly lower pain score (pooled SMD: 0.20, 95% CI, 0.01 to 0.39, p = 0.041, I2 = 58%, N = 1187) and higher patient preference but invalid anesthesia at the dorsal proximal digit. No significant differences were observed in the onset of anesthesia, adjacent digit invalid numbness, distal phalanx invalid anesthesia, additional injection rate, and adverse effects. In conclusion, this meta-analysis of RCTs showed that the single-volar injection was associated with a lower pain sensation during injection and higher patient satisfaction with a reduced anesthetic effect over the proximal dorsal phalanx. Further high-quality RCTs with a higher number of cases are needed to validate our results.

Effectiveness and adverse reactions to subcutaneous immunotherapy in children with allergic rhinitis/asthma.

OBJECTIVE: Adverse reactions, which are mostly local and rarely systemic, can be seen during subcutaneous immunotherapy (SCIT). It was not possible to continue SCIT at times due to systemic reactions. The purpose of the present study was to identify the incidence and risk factors associated with adverse reactions during subcutaneous allergen-specific immunotherapy (AIT). METHODS: A total number of 344 patients under 18 years old with allergic rhinitis and/or asthma who underwent SCIT between 2005 and 2021 were included in the study. Demographic characteristics of the patients, laboratory findings [Total Immunglobulin E(IgE), aeroallergen prick test, inhaler, and allergen specific IgE(sIgE) and eosinophil counts], and adverse events observed during AIT were recorded retrospectively. Descriptive and univariate/multivariate logistic regression analyses were used to identify risk factors for adverse events. RESULTS: Among 344 patients, 33.4% (n = 115) were female, mean age was 133.1 ± 41.0 months, and 42.2% (n = 145) were >12 years old. One hundred-thirty eight (40.1%) of the patients were mono-sensitized, 47 (13.7%) had asthma, 207 (60.2%) allergic rhinitis, and 90 (26.2%) asthma and allergic rhinitis. Single allergen content was administered to 187 (54.4%) patients (62 mite, 114 grass mix, 11 olea), and multiple allergens to 157 (45.6%) patients (121 pollen mix, 36 other (mite/alternaria)]. A total number of 33.008 injections were administered. 840 adverse reactions (262 (31.1%) at up-dosing phase, 578 (68.8%) at maintenance phase) in 195 (56.7%) patients were observed. Among the adverse reactions, 632 (75.2%) were local, 160 (19%) large local, and 48 (5.7%) (39 at maintenance, 9 at up-dosing) (in 31 patients) were systemic (28 Grade 1, 12 Grade 2, 8 Grade 3). Adrenalin was administered to 8 patients with Grade 3 systemic reaction (8/33008; %0.024). Adverse reactions, especially local ones, were seen more frequently in children under 12 years old (p < 0.001). Patients sensitized with grass pollen (p:0.01) and mite (p:0.004), and those who had received SCIT with pollen mixture had more adverse reactions than the others. More adverse reactions were observed in SCIT containing calcium-phosphate as adjuvant (p: 0.01). Local reactions were risk factors for large local (OR = 3.591, %95 CI:2.064-6.247, p < 0.001) and systemic (OR = 2.190, %95 CI:1.005-4.722 p = 0.046) reactions at univariate analyses. Total nasal symptom scores, Visual Analog Scale and asthma symptom control test decreased after one year of treatment (p < 0.01). CONCLUSION: SCIT is a safe and effective treatment method in childhood that leads to improvements in all nasal symptoms and asthma after one year of treatment.

Efficacy of subcutaneous Levothyroxine in a case of refractory hypothyroidism: A case report.

RATIONALE: Daily oral synthetic levothyroxine (LT4) is the main treatment for hypothyroidism, which, in most cases, allows the regression of symptoms and the normalization of the thyroid function. However, rarely, despite a high dose of oral LT4, hypothyroidism persists and is called refractory hypothyroidism. Intravenous or intramuscular treatment is then often necessary. We report the case of a patient with refractory hypothyroidism successfully treated with subcutaneous LT4. INTERVENTIONS AND OUTCOMES: After 4 weeks of weekly intravenous injections of 200 µg LT4 in complement to the oral treatment, thyroid balance was improved (TSH: 21.8 mIU/L). We tested the replacement of intravenous with subcutaneous injections of LT4 and gradually increased injection frequency from 1 to 3 injections per week (600 µg/week). Simultaneously, oral treatment was gradually tapered off, and within a few months, thyroid function tests were normalized. Two years later, hormone levels remained normal without symptoms of hypothyroidism. The only side effect was a local reaction in the first few weeks of injections, which spontaneously resolved. LESSONS: In this case of unexplained oral LT4 malabsorption, subcutaneous injection allowed a self-administrated physiological dose of LT4 3 times weekly. Considering the efficacy of subcutaneous injection of LT4, this treatment could be a safe and easy alternative for patients with malabsorption.

Hyperbaric oxygen therapy for treatment of a late presenting ischaemic complication from hyaluronic acid cosmetic filler injection.

Vascular compromise and resulting ischaemic injury are known rare complications of cosmetic filler injections. Most hyaluronic acid vascular compromises present early and can be treated effectively by hyaluronidase. Here we present a case of ischaemic wound and mucosal necrosis after cosmetic facial hyaluronic acid injection that appeared within hours of injection but was not diagnosed and treated for 5 days. At day 5, the patient was treated with hyaluronidase injection immediately followed by 14 sessions of daily hyperbaric oxygen therapy (HBOT). Despite the delayed treatment, the patient had essentially complete recovery and the hyperbaric therapy was overall well-tolerated. Our case report suggests that hyaluronidase injection with concurrent daily HBOT sessions may be effective to allow recovery from late-presenting filler ischaemic complication. Furthermore, given the safety profile of HBOT, we suggest a more deliberate approach to this modality as a therapeutic adjunct by cosmetic practitioners when similar complications arise.

miRNA profiles change during grass pollen immunotherapy irrespective of clinical outcome.

Background: Subcutaneous immunotherapy (SCIT) is widely used in the treatment of allergic rhinitis (AR). This study aimed to determine the expression of 48 miRNAs in patients with AR undergoing grass pollen SCIT and investigate relations with clinical outcomes. Methodology: Expression of selected miRNAs was determined using RT-PCR in the full blood of 16 patients with AR and seven healthy controls. Results: miR-136, miR-208 and miR-190 were upregulated in the AR group. After 6 months of SCIT, significant downregulation of some proinflammatory miRNAs and upregulation of several miRNAs regulating Th1/Th2 balance were found. No differences were found between good and poor responders. Conclusion: miRNAs may play a regulatory role in SCIT, leading to tolerance induction.

Background: Subcutaneous immunotherapy is widely used in the treatment of allergic rhinitis (AR). MicroRNAs (miRNAs) are small molecules controlling gene expression. Their role in the process of immunotherapy is not yet well understood. This study aimed to investigate the expression of 48 miRNAs in patients with AR undergoing grass pollen immunotherapy and relations between miRNAs and clinical outcomes. Methodology: The expression of selected miRNAs was determined in the blood of 16 patients with AR and seven healthy people. Results: Three miRNAs were found to be overproduced in allergic patients. During immunotherapy, the production of several proinflammatory miRNAs was reduced while those responsible for allergen tolerance were produced in larger amounts. Conclusion: miRNAs may play an important role in immunotherapy, leading to better tolerance of allergens.

Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study.

OBJECTIVES: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. METHODS: The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. RESULTS: The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of >0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of >0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. CONCLUSION: Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.

Population Pharmacokinetics and Pharmacodynamics of Burosumab in Adult and Pediatric Patients With X-linked Hypophosphatemia.

Burosumab is a fully human monoclonal antibody against fibroblast growth factor 23, which has been approved to treat X-linked hypophosphatemia (XLH) in adult and pediatric patients. The present work describes the pharmacokinetics (PK) of burosumab and the pharmacokinetic-pharmacodynamic (PK-PD) relationship between burosumab and serum phosphorus in adult and pediatric patients with XLH. A total of 2844 measurable serum concentrations of burosumab and 6047 measurable serum concentrations of phosphorus in 277 subjects from 9 clinical studies were included in the population PK and PK-PD modeling. The serum concentration of burosumab following a subcutaneous administration was well described by a population PK model comprising a first-order absorption, 1-compartmental distribution, and a linear elimination. The relationship between serum burosumab and serum phosphorus was adequately described by a sigmoid maximal efficacy model. Body weight was the only covariate associated with PK and PK-PD parameters. No other intrinsic factors affected PK or PK-PD relationship in adult and pediatric patients with XLH. Further simulations helped to guide the dosing regimen of burosumab in adult and pediatric patients with XLH including age groups with no clinical data.

A 52 weeks dupilumab treatment for moderate to severe atopic dermatitis in Korea: long-term efficacy and safety in real world.

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