Local Side Effects Research Articles

Advances in the study of nebulized tranexamic acid for pulmonary hemorrhage.

Pulmonary hemorrhage is a life-threatening condition characterized by blood leakage into lung tissues, leading to severe respiratory distress. Nebulized tranexamic acid (TXA) has emerged as a promising treatment option for pulmonary hemorrhage due to its localized hemostatic effects and minimal systemic side effects. This review aims to summarize the research progress on the effectiveness and safety of nebulized TXA in pulmonary hemorrhage. A comprehensive search of the Embase, PubMed, and Scopus databases was conducted to identify relevant studies published between the date of inception of each database and November 2023. A comprehensive search was conducted in the PubMed, Embase, Scopus, and Google Scholar databases using the following keywords: "hemoptysis," "haemoptysis," "pulmonary hemorrhage," "tranexamic acid," "antifibrinolytic," "nebulize," and "inhale." Additional articles were identified by reviewing the references of the retrieved studies. Studies were selected based on their focus on the application of nebulized TXA for pulmonary hemorrhage. The authors and dates of publication, study type, patients, diseases, intervention and main outcomes of these papers are tabulated. This consisted of two randomized controlled trials (RCTs), six case series, and nine case reports. The commonly used dosage of nebulized TXA in the studies reviewed was 500mg/5ml, administered 3-4 times daily. Evidence suggests that nebulized TXA effectively controls bleeding in pulmonary hemorrhage with a hemostatic efficacy comparable to systemic administration, but with a lower risk of venous thrombosis. Safety data indicates that nebulized TXA is generally well-tolerated, with no significant systemic adverse reactions reported. Local reactions, such as bronchospasm, were rare and resolved with short-term bronchodilator treatment. Nebulized TXA appears to be an innovative and minimally invasive therapy for pulmonary hemorrhage, providing targeted hemostatic effects with a favorable safety profile. However, the predominance of small-scale studies and case reports highlights the need for large-scale, high-quality research to establish standardized guidelines.

Multiwavelength photobiomodulation in atrophic age-related macular degeneration.

To evaluate photobiomodulation (PBM) safety and efficacy in patient with atrophic AMD and to explore tissue effects using Spectrally Resolved Autofluorescence (SrAF) to identify a potential biomarker indicative of mitochondrial activity, the primary PBM target. This retrospective, non-comparative case series involved six eyes of five patients with atrophic AMD, conducted at the Medical Retina and Imaging Unit, IRCCS San Raffaele Hospital in Milan, Italy. At baseline and follow-ups (after one and three months) a complete ophthalmological assessment and multimodal imaging, including spectrally resolved autofluorescence (SrAF), were performed. PBM treatment (Valeda Light Delivery System - LumiThera) was administered in nine sessions over three weeks. The SrAF images were analyzed to evaluate the effect of the treatment. Six eyes of five patients with atrophic AMD received PBM at baseline. Best corrected visual acuity (BCVA), mean central macular thickness (CMT), mean retinal sensitivity on microperimetry and the atrophic area have remained stable. No eyes developed foveal atrophy after the treatment. The image analysis in SrAF showed an increase in the highlighted area of 4.89% after one month and 17.11% after three months. No adverse systemic or local side effects were reported. PBM is a safe treatment for the human retina. The evaluation of the retinal area within the green light spectrum (575 nm) in SrAF is a potential indirect biomarker of mitochondrial activity and could be used to assess treatment efficacy in clinical studies.

Dry powder inhaler deposition in the larynx and the risk of steroid inhaler laryngitis: A computational fluid dynamics study

Dry Powder Inhalers (DPIs) are a mainstay in the treatment of obstructive respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Deposition of inhaled corticosteroids in the larynx elicits local side effects, potentially leading to steroid inhaler laryngitis. The objective of this study was to estimate the dose of DPIs that are deposited in the larynx relative to other regions of the respiratory tract using computational fluid dynamics (CFD). An anatomically accurate model of the airways (mouth to main bronchi) was constructed based on medical imaging of a healthy adult. Respiratory airflow and particle transport were simulated for constant inhalation rates of 30, 45, and 60 L/min. Two turbulence models were compared, namely the large eddy simulation (LES) and the k−ωSST models. DPIs were assumed to generate an aerosol cloud with a log-normal particle size distribution characterized by the mass median aerodynamic diameter (d50) and geometric standard deviation (σg). We compared two commercial DPIs, namely DPI 1 had a large particle size (d50 = 50 μm, σg=2.55) and DPI 2 had a small particle size (d50 = 2 μm, σg=1.99). The laryngeal dose was 1.6-to-3.8-fold higher than the bronchial dose for DPI 1, while the laryngeal and bronchial doses (units of mass per unit surface area) were similar for DPI 2 for both turbulence models and all inhalation rates. The choice of turbulence model had little impact on the total extrathoracic deposition, but a significant impact on regional doses, with the LES model predicting higher larynx-to-bronchi relative doses than the k−ω model. Our prediction that the larynx is a hotspot for DPI deposition is consistent with the observation of laryngeal side effects in DPI users. Importantly, our simulations suggest that DPIs with larger particles (d50 = 50 μm) may increase the risk of steroid inhaler laryngitis.

INNV-34. APPLICATION OF 200 KHZ TUMOR TREATING FIELDS (TTFIELDS) IN PATIENTS WITH INFRATENTORIAL HIGH-GRADE GLIOMA: CASE SERIES

Abstract BACKGROUND 200 kHz Tumor Treating Fields (TTFields) therapy is FDA-approved for supratentorial newly-diagnosed and recurrent glioblastoma. However, reports of its application in patients with infratentorial high-grade glioma (HGG) are rare. Based on computational modeling, the therapeutic field strength (~1 V/cm peak-to-peak) is thought to be achievable for infratentorial HGG. METHODS Two patients with infratentorial HGG received off-label 200 kHz TTFields therapy with the Optune® device (Novocure, Ltd.). To reduce impaired range of motion of the neck, the electrode transducer arrays were “skeletonized” by cutting a portion of the adhesive material surrounding them. Application of the electrode arrays was performed with the neck in flexion, to further promote neck range of motion. Cloth tape was used for reinforcement as necessary. Electrode arrays were changed every 2-3 days. We report the results of patient survival and adverse events. RESULTS Patient 1: 22-year-old man with high-grade diffuse pontine glioma with recurrences and prior treatments (including radiation, temozolomide, lomustine, and dopamine receptor D2 [DRD2] antagonist), tolerated TTFields combined with systemic treatment (initially with a bi-functional DNA alkylating agent; subsequently with temozolomide and bevacizumab) for 5 months with stable disease for 4 months. He experienced grade 1 rash of the neck. Patient 2: 58-year-old woman with diffuse glioma of the brainstem (H3K27M-mutated) with multiple recurrences and prior treatments (including concurrent radiation and temozolomide, and DRD2 antagonist), tolerated TTFields combined with systemic treatment (lomustine and bevacizumab). The TTFields infratentorial layout was iteratively modified with respect to placement of the electrode transducer arrays, for improved tolerability. With the TTFields+systemic combination therapy, the patient was stable for 8 months with no local TTFields-related side effects. CONCLUSIONS We provide initial post-marketing evidence that off-label use of 200 kHz TTFields in infratentorial HGG is safe and feasible. Prospective studies are necessary to validate the efficacy of this approach.

Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. Toll-like receptor (TLR) agonists can also reactivate immunity, and the TLR9 agonist CpG oligodeoxynucleotide (CpG-ODN) has been effective in treating lung cancer in animal models. In this study, we investigated the use of TLR9 agonist CpG-ODN as LAM immunotherapy in combination with checkpoint inhibitor anti-PD1 and standard of care rapamycin, and determined the immune mechanisms underlying therapeutic efficacy. We used survival studies, flow cytometry, ELISA, and histology to assess immune response and survival after intranasal treatment with CpG-ODN in combination with rapamycin or anti-PD1 therapy in a mouse model of metastatic LAM. We found that local administration of CpG-ODN enhances survival in a mouse model of LAM. We found that a lower dose led to longer survival, likely because of fewer local side effects, but increased LAM nodule count and size compared with the higher dose. CpG-ODN treatment also reduced regulatory T cells and increased the number of T-helper type 17 cells as well as cytotoxic T cells. These effects appear to be mediated in part by plasmacytoid dendritic cells because depletion of plasmacytoid dendritic cells reduces survival and abrogates T-helper type 17 cell response. Finally, we found that CpG-ODN treatment is effective in early-stage and progressive disease and is additive with anti-PD1 therapy and rapamycin. In summary, we have found that TLR9 agonist CpG-ODN can be used as LAM immunotherapy and effectively synergizes with rapamycin and anti-PD1 therapy in LAM.

Comparison of immune response parameters between homologous and heterologous COVID-19 vaccines: A scoping review

It has been over 4 years since the emergence of the coronavirus disease 2019 (COVID-19) pandemic. This highly contagious respiratory infection has endangered the health of millions and significantly impacted healthcare systems and economies. Vaccines are believed to confer immunity against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, reducing both the severity of infection and the spread of the virus. Within a short period, various COVID-19 vaccines were developed and extensively tested before being approved by the WHO for distribution and administration. Now, due to concerns about emerging new strains of the virus and limited vaccine availability, a heterologous vaccine strategy is being deployed. Therefore, this paper aims to conduct a scoping review of existing evidence to compare the immunogenicity of heterologous vaccines with homologous vaccines and determine which confers better immunity against COVID-19. A literature search was conducted across three electronic databases (Ovid MEDLINE, PubMed, and Scopus). The retrieved studies were screened for relevance and eligibility using the online platform Covidence. A total of 31 articles were shortlisted for data extraction and analysis. Among these, 21 were observational studies, and 10 were clinical trials. The analysis demonstrated that participants who received heterologous vaccination regimens generated higher levels of IgG antibodies against the spike protein of SARS-CoV-2, antibodies targeting the receptor-binding domain, and T-cell responses compared to those who received homologous vaccination regimens. Furthermore, heterologous vaccination produced higher titers of neutralizing antibodies against several variants of concern (VOC), including Alpha, Beta, Gamma, Delta, and Omicron. No severe vaccine-related adverse events were reported in these studies, and common local and systemic side effects were manageable. Overall, heterologous vaccination regimes induced strong humoral and cellular immunity, comparable to homologous vaccination regimes, with stronger neutralizing antibody activity against VOCs.

Update in the diagnosis and treatment of actinic keratosis

Actinic keratosis (AK) is among the most common conditions in dermatology in an increasingly aging population. However, the presence of severe field cancerization with large treatment fields showing multiple lesions with distinct features often poses atherapeutic challenge. The most accurate possible characterization of the treatment field, risk assessment concerning the occurrence of cutaneous squamous cell carcinoma, and knowledge of the efficacy and local side effects of the available interventions are of paramount importance for effective management and preventive efforts. This article summarizes current developments in the diagnosis and treatment of AK and discusses their application in everyday clinical practice. In particular, the focus is on the increasing value of non-invasive diagnostic techniques like "line-field" confocal optical coherence tomography, and the recently approved topical agents tirbanibulin 1% ointment and 5‑fluorouracil 4% cream, as well as current developments of photodynamic therapy and prevention.

Role of Phytochemicals in the Management of Atopic Dermatitis: A Comprehensive Review

Abstract: Atopic dermatitis is a chronic inflammatory skin condition that affects millions of people around the world. In the past decades, phytochemicals have gained attention for the treatment of atopic dermatitis due to their inflammatory, antioxidant, and immunomodulatory properties, which could be beneficial in alleviating the suffering associated with atopic dermatitis. Although various conventional treatments, such as immune modulators and biologicals, are available for the treatment of atopic dermatitis their effectiveness can be limited due to some adverse effects. The present review aimed to explore the various phytochemicals to be identified as a complementary and alternative treatment option for the management of atopic dermatitis. Phytochemicals offer the potential advantage of reducing both local and systemic side effects associated with long-term use of corticosteroids, as well as addressing the higher costs of biological drug therapies. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science to identify the pharmacologically proven phytochemicals for the management of atopic dermatitis by covering articles published from 2015 to 2023. Various phytochemicals, such as berberine, piperine, ferulic acid, baicalin, vasicine, neferine, kaempferol, α- Boswellic Acid, gallic acid, etc., werebe highlighted for their potential therapeutic effects in atopic dermatitis. In conclusion, phytochemicals present a promising, safe, complementary, and alternative treatment option for atopic dermatitis management.

Functionalized Amyloid‐Like Protein Nanofilm‐Mediated Synergistic Disulfidptosis and Photodynamic Therapy for Preventing Postoperative Recurrence of Colorectal Cancer

Colorectal cancer (CRC) has a postoperative recurrence rate of up to 50%. Local treatment at the surgical site offers a new strategy to prevent recurrence, minimizing systemic side effects. However, these treatments often face issues like poor stability, insufficient targeting, and significant local side effects. Research shows glucose starvation can induce disulfidptosis, a novel cell death pathway, in CRC cells, suitable for precise intervention in residual tumor cells postsurgery. This study develops a biocompatible 2D therapeutic platform using amyloid‐like protein nanofilm technology for precise local synergistic intervention in disulfidptosis and photodynamic therapy (PDT) after CRC surgery. The nanofilm boasts excellent drug‐loading capacity, enzyme activity retention, ultrathin dimensions, wet adhesion, and biocompatibility. A model simulating incomplete tumor resection post‐CRC surgery shows that the GCI@nanofilm effectively inhibits recurrence through an enzyme‐catalyzed cascade reaction inducing disulfidptosis and synergizing with PDT. In summary, GCI@nanofilm overcomes multiple challenges in local postsurgical intervention, providing a foundation for precise and efficient treatment of residual tumors.

Application of Corticosteroids in Dentistry: A Review

ABSTRACT Corticosteroids are crucial in dentistry for their anti-inflammatory and immunosuppressive properties, aiding in managing conditions such as oral lichen planus, recurrent aphthous stomatitis, and post-operative inflammation. By inhibiting pro-inflammatory mediators and immune cell activity, they offer significant symptomatic relief and promote healing. However, potential systemic and local side effects necessitate cautious application. This article explores the use of corticosteroids in routine dental practice.

Neuro-musculoskeletal side effects related to COVID-19 vaccines; A cross sectional study in Iranian healthcare workers

IntroductionThis study aimed to evaluate neuro-musculoskeletal adverse events related to COVID-19 vaccines in Iranian healthcare workers. MethodsIn this cross-sectional survey, a questionnaire was used, including patients’ demographic information, vaccination information, and local, flu-like, and neuro-musculoskeletal side effects of vaccines. All data were extracted and analyzed by SPSS ver.24. ResultsA total of 500 healthcare workers (381 females, and 119 males), with a Mean ± SD age of 38.06 ± 9.22 years old were recruited; 341 subjects (68.2 %) were vaccinated by Sputnik-V vaccine, 95 subjects (19 %) with AstraZeneca, 40 subjects (8 %) with Sinopharm, and 24 (4.8 %) with Baharat COVID-19 vaccine. Out of 500 participants, COVID-19 vaccines' side effects were reported in 428 subjects (85.6 %) including 339 subjects (67.8 %) with local side effects, 342 subjects (68.4 %) subjects with flu-like side effects, 66 subjects (13.2 %) with neurologic, and 291 subjects (58.2 %) with musculoskeletal side effects. Local pain (67.6 %), fatigue (61.2 %), generalized pain (47.8 %), headache (38.8), upper and lower myalgia (44 %, 36 %), and low back pain (26.8 %) were the most common side effects reported by COVID-19 vaccine recipients. There were significant associations between neuro-musculoskeletal side effects with patients’ sex (P = 0.001), categorized age (less and more than 40 years., P = 0.002), and COVID-19 vaccine types (P < 0.001). ConclusionsAmong all the neurological and musculoskeletal side effects, upper limb paresthesia, and upper limb myalgia alongside low back pain were the most frequent respectively. No serious side effects requiring medical attention or hospitalization were reported by participants.

Local and systemic side effects of COVID-19 vaccine in Tunisian cancer patients: A prospective single center study.

We aimed to evaluate the local and systemic side effects of the COVID-19 vaccine in cancer patients. we conducted a cross-sectional study including cancer patients treated at Habib Bourguiba Hospital in Sfax, Tunisia between January and March 2022. Patients should have received at least 1 dose of a COVID-19 vaccine. We interviewed a total of 106 patients, of which 80.2% were actively treated. Mean age was 52.52. Patients were vaccinated by the Pfizer/BioNTech in 59.8% and the Oxford/AstraZeneca in 22.5%. The most frequent grade 1 or 2 adverse events occurring within 7 days were: pain at injection site (71.7%) and fatigue (38.7%). Only 2 patients developed grade 3 toxicity following vaccination. The most systemic side effects were fatigue (35.8%), fever (25.4%), headache (16.9%) and arthralgia (15.1%). They were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine (69.6% vs 42.6%; p = 0.03). Risk of any grade toxicity (local or systemic) following the first dose was correlated with female sex (p = 0.033). Our study showed that systemic side effects were more common after the first dose of Oxford/AstraZeneca vaccine compared to the Pfizer/BioNTech vaccine in cancer patient, with the predominance of any grade of local or systemic toxicity in women.

Impact of inflammatory skin conditions on the biological profile of plasma rich in growth factor

Plasma rich in growth factors (PRGF) can be used over patients suffering from dermatoses due to its anti-inflammatory effect. However, this population group might present soluble autoimmune components and there is limited information about the effect of chronic skin inflammation on PRGF bioactive properties. With the aim of characterizing PRGF composition, PRGF from healthy (H) donors and patients with atopic dermatitis (AD), psoriasis (PS), or lichen sclerosus (LS) was obtained. In order to reduce the inflammatory component, leukocyte exclusion and heat-inactivation (Immunosafe) were tested. Haematological-serological parameters, platelet functionality, clot microstructure, protein content and bioactivity were determined. Mean values and 95 % confidence intervals (mean[95 % CI]) were computed for key haematological parameters, such as platelet (410×103/mm3[371–449]) and leukocyte content (205×103/mm3[148−262]), platelet activation (resting: 4.3 %[3.1–5.5] and activated: 97.4 %[96.7–98.0]), the concentration of plasma proteins and morphogens, including immunoglobulins A (210.7 mg/dL[191.8–229.6]), G (933.1 mg/dL[887.2–978.9]), E (783.5 mg/dL[54.4–1512.6]), and M (115.0 mg/dL[97.1–133.0]), Complement Protein (31.6 mg/mL[26.6–36.6]), C-Reactive protein (3.1 mg/L[2.0–4.1]), TGF-β1 (35975.6 pg/mL[34221.3–37729.8]), fibronectin (146410.0 ng/mL[136518.3–156301.7]), PDGF-AB (13308.5 pg/mL[12401.0–14216.0]), CD40L (2389.3 pg/mL[1887.7–2890.8]), IL-4 (0.12 pg/mL[0.07–0.18]), IL-13 (35.4 pg/mL[21.0–49.7]), IL-1β (0.09 pg/mL[0.06–0.11]) and TNF-α (0.31 pg/mL[0.24–0.38]), and also for cell proliferation (332.9ngDNA/mL[317.4–348.3]), viability (135.6 %[132.0–139.2]) and migration (103.8cells/mm2[98.3–109.3]). Plasma from AD donors presented increased Immunoglobulin E (IgE) that was significantly reduced after Immunosafe along with the complement system and autoantibodies. Platelet functionality was altered for AD, but no microstructure differences were identified. Pathological groups presented reduced concentration of fibronectin (AD/LS) and Platelet-Derived Growth Factor (PDGF-AB) (P). Immunosafe treatment reduced Cluster of Differentiation 40 Protein (CD40L), interleukin 1β (IL-1β), and Tumor Necrosis Factor α (TNF-α) concentrations. Fibroblasts supplemented with PRGF obtained from pathological patients (PS/AD) showed reduced viability but Immunosafe increased cell proliferation and migration in SP (LS) and L-SP samples (PS/AD). In conclusion, PRGF derived from pathological patients present autoimmune components, but heat-inactivation or leukocyte exclusion could minimize local side effects.

Prevalence of COVID-19 vaccines side effects among health care workers in Kirkuk City, Iraq

Frequent local and general side effects were revealed after vaccination with COVID-19 vaccine, which played a role in public confidence in and acceptance of the vaccine since the evidence source for the safety of the vaccines and their side effects were exclusively provided only from manufacturer-funded researches. This study aimed to assess the prevalence of COVID-19 vaccines side effects among health care workers in Kirkuk City, Iraq. This cross-sectional study was done in governmental hospitals in Kirkuk City/Iraq from May 7, 2022 to August 15, 2022 among 373 healthcare workers (only those who were vaccinated with the COVID-19 vaccine). The data were analyzed through the statistical package for social sciences (SPSS) program version 23.0. Total of 246 (66%) healthcare workers experienced at least one side effect following the COVID-19 vaccination. Reported side effects among females were higher (70.1%) than males (60.4%) and they were a little higher (67.2%) among participants with age ≤40 years. The most repeated side effects were general fatigue, injection site pain, and headache. In conclusion the majority of the reported side effects were mild to moderate in severity and not considered life-threatening. The rate of COVID-19 side effects was lower among the participants who received Sinopharm's COVID-19 vaccine in comparison to others vaccines.

Unveiling the science behind erectile dysfunction topical therapy: investigating transdermal papaverine as a novel treatment approach.

Erectile dysfunction is among the most prevalent urologic issues affecting men globally and is characterized by a high incidence rate. This condition significantly affects the quality of life of patients and their sexual partners. Due to the interactions, contraindications, and side effects associated with systemic drugs, recent research has increasingly focused on topical and transdermal medications for the treatment of erectile dysfunction. Based on previous studies, this article examines papaverine in terms of local effectiveness, methods of increasing therapeutic efficiency, possible local side effects, and evaluation of its various formulations. Among these approaches, notable strategies include using novel formulations and nanoformulations as compared with classic ones, employing permeation enhancers, and combining treatments with other oral and topical drugs with synergistic mechanisms. These methods aim to improve transdermal papaverine's bioavailability and therapeutic efficacy while minimizing side effects and enhancing patient compliance. Transdermal papaverine may not be as effective as its injectable form, but the treatment path is more pleasant, with less pain and fewer side effects for patients. For this reason, using solutions that remove the penile skin and fascial absorption barrier can be very effective.

Impact of SARS-CoV-2 vaccination in patients with vascular liver diseases: Observations from a VALDIG multicenter study

Background and AimsPatients with vascular liver diseases(VLD) are at higher risk for both severe courses of COVID-19 disease and thromboembolic events. The impact of the SARS-CoV-2 vaccination in VLD patients has not been described and represent the aim of our study. MethodsInternational multicenter prospective observational study in patients with VLD analyzing the incidence of COVID-19 infection after vaccination, severity of side effects, occurrence of thromboembolic events and hepatic decompensation. In a subgroup of patients, the humoral and cellular responses to vaccination were also analyzed. Results898 patients from 14 European centers part of the VALDIG network were included, 872(97.1%) patients received two vaccine doses (fully vaccinated), and 674(75.1%) three doses.Of the total cohort, 151/898 had a COVID-19 infection prior to vaccination, of which 9/151(5.9%) were re-infected. Of the previously 747/898 patients who were not previously infected, 11.2%(84/747) were diagnosed with a COVID-19 infection during the study period.Two infected patients required ICU admission and infection was fatal in two fully vaccinated patients. Main adverse effects were reported in around 40% of patients, being local side effects the most frequent.During the study period, 31(3.5%) patients had thromboembolic events and 21(2.3%) hepatic decompensations. No vaccine-induced-thrombocytopenia (VITT) case was reported.Vaccine immunogenicity was assessed in 36 patients; seroconversion reached 100% and IFNy-T cell responses significant increased post two mRNA-1273 vaccine doses. ConclusionPatients with VLD seems to have a preserved immune response to SARS-CoV-2 vaccination, which appears to be safe and effective in preventing severe COVID-19 infection. Our study cannot definitively establish a direct link between vaccination and thrombotic events, however the contribution of vaccination as a cofactor in VLD remains to be elucidated.

The effect of high-definition transcranial direct current stimulation on pain in somatic symptom disorder with predominant pain: A randomized single-blind sham-controlled crossover study

Somatic symptom disorder with predominant pain (SSD-P) is a commonly encountered disorder, yet treatment options often yield unsatisfactory outcomes. Transcranial direct current stimulation (tDCS) has proven useful in chronic pain conditions and may hold potential for treating somatoform pain. High-definition tDCS (HD-tDCS) offers more precise cortical stimulation than conventional tDCS. However, this modality has not been extensively studied in SSD-P. Consequently, this study aims to assess the effects of a novel HD-tDCS protocol on pain and other associated variables in patients with SSD-P. The Institute Ethics Committee approved the study, which was also registered in the Clinical Trials Registry of India. A single-blind, sham-controlled, crossover study design was employed. Thirty right-handed patients with DSM-5 diagnosis of SSD-P, aged 18 &amp;ndash; 60 years and receiving stable treatment, were enrolled through consecutive sampling. After simple randomization, two repeated, short-interval sessions (2 mA, 20 min each) of either active or sham HD-tDCS were administered, followed by a washout period of 7 days and a subsequent crossover. Assessments were conducted at baseline, week 1, and week 2. Participants in active and sham arms were comparable on all baseline parameters. At the end of the 1st week, patients in the active group showed significant improvement in the study variables compared to the sham group. By week 2, all participants, irrespective of being in the active or sham arm, demonstrated a statistically significant difference (Cohen&amp;rsquo;s d &gt; 0.8) in pain and associated parameters such as depression, anxiety, pain-related interference, burden, and disability (P &lt; 0.01). Transient mild local side effects such as burning, pain, and itching were noted, with no cognitive side effects reported. In conclusion, this novel HD-tDCS protocol is effective in reducing pain in patients with SSD-P, with sustained effects up to 1 week.

Budesonide aqueous nasal spray: an updated review in managing chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent medical condition. Type 2 inflammation signs CRSwNP in western countries. Type 2 inflammation leads to nasal airflow limitation. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS); it has been launched in the early 1980s. BANS is indicated for treating allergic rhinitis, nonallergic rhinitis, and nasal polyps (both as treatment and prevention after surgery). Consolidated evidence documented its efficacy in treating CRSwNP. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with CRSwNP recommend using INCS as the first line in many situations. In particular, patients may assess the perception of symptoms' severity using the Visual Analog Scale (VAS). A score >5/10 means uncontrolled symptoms in both diseases and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In addition, BANS may adequately integrate surgery and biologics for CRSwNP management. In conclusion, BANS represents a valuable option in managing patients with type 2-mediated CRSwNP.

Local side effects during sublingual allergen-specific immunotherapy and pathogenetically based methods for their correction (Review)

Introduction. The study of the effectiveness and safety of allergen-specific immunotherapy remains relevant due to the emergence of a personalized approach in allergology and new dosage forms. Adverse reactions during sublingual allergen-specific immunotherapy are the leading reason of treatment discontinuation. Understanding the mechanisms of side effects and knowing how to overcome them allows us to achieve better tolerability of allergen-specific immunotherapy and maintain patient compliance.The aim of the review is to combine the available literature data on the frequency, nature, and pathogenetic basis of adverse events during sublingual allergen-specific immunotherapy and to consider options for their prevention and treatment.

LOCAL ANTIBACTERIAL TREATMENT IN PATIENTS WITH INFECTED PANCREATIC WALLED-OFF NECROSIS: A SYSTEMATIC REVIEW

Introduction. Systemic antibacterial treatment in patients with infected pancreatic necrosis often fails to resolve the infection due to impaired penetration in necrotic areas. The endoscopic step-up approach based on endoscopic transmural drainage followed, if necessary, by endoscopic necrosectomy has become the standard of care in patients who do not respond to systemic antibiotics. The additional local administration of antibiotics may increase their concentration in necrotic tissue. Aim. To evaluate the efficacy of local infusion of antibacterial agents to the site of infection in addition to systemic treatment after endoscopic drainage to resolve the infection and decrease the need for necrosectomy in patients with walled-off infected pancreatic necrosis. Materials and methods. Major databases were searched for clinical studies assessing the efficacy of local perfusion of antibiotics for the treatment of infected pancreatic necrosis. Results. Four studies were included, two cohort studies and two single-case reports. The majority of patients with infected pancreatic necrosis developed polymicrobial infection. More than one-third of patients additionally had fungal infection. Local irrigation of antibiotics in patients with infected pancreatic necrosis resulted in the eradication of bacteria and fungi, avoiding necrosectomy in almost half of cases. No local or systemic side effects were reported with this strategy. Conclusions. Evidence evaluating the efficacy of local antibiotics for the treatment of infected pancreatic necrosis is scarce. Simultaneous local and systemic administration of antibiotics after endoscopic drainage could reduce the need for necrosectomy. Randomized clinical trials are needed to evaluate the impact of adding local to systemic antibiotics in the prognosis of patients with infected pancreatic necrosis.