Local Side Effects Research Articles

Medial or Lateral, That Is the Question: A Retrospective Study to Compare Two Injection Techniques in the Treatment of Knee Osteoarthritis Pain with Hyaluronic Acid.

Background: Mild-to-moderate knee osteoarthritis (KOA) can be successfully treated using intra-articular hyaluronic acid (IA-HA). The medial infrapatellar (MIP) approach and lateral infrapatellar (LIP) approach are two of the most used techniques for performing IA-HA, but it is still not clear which one is preferable. Objectives: The study aims to find the best knee injection technique between MIP and LIP approaches. Methods: In total, 161 patients were enrolled, divided into two groups (MIP or LIP). Each technique was performed once a week for three weeks. Patients were evaluated using the Numeric Rating Scale (NRS), Knee Injury and Osteoarthritis Outcome Score (KOOS) and Roles and Maudsley Score (RMS) at T0 (before the first injection), T1 (one week after the third injection) and T2 (six months after). Results: NRS, KOOS and RMS showed a statistically significant improvement in both groups at all the detection times, without significant differences. No differences were detected between the groups in terms of systemic effect effusions, while the MIP group presented a mildly higher number of bruises in comparison with the LIP group (p = 0.034). Conclusions: Both the IA-HA techniques are equally effective in measured outcomes. The MIP approach seems to produce some local and transient side effects. So, the choice of the LIP or MIP approach depends on the operator's skill and experience.

D-galacto-D-mannan-mediated Dectin-2 activation orchestrates potent cellular and humoral immunity as a viral vaccine adjuvant.

Conventional foot-and-mouth disease (FMD) vaccines have been developed to enhance their effectiveness; however, several drawbacks remain, such as slow induction of antibody titers, short-lived immune response, and local side effects at the vaccination site. Therefore, we created a novel FMD vaccine that simultaneously induces cellular and humoral immune responses using the Dectin-2 agonist, D-galacto-D-mannan, as an adjuvant. We evaluated the innate and adaptive (cellular and humoral) immune responses elicited by the novel FMD vaccine and elucidated the signaling pathway involved both in vitro and in vivo using mice and pigs, as well as immune cells derived from these animals. D-galacto-D-mannan elicited early, mid-, and long-term immunity via simultaneous induction of cellular and humoral immune responses by promoting the expression of immunoregulatory molecules. D-galacto-D-mannan also enhanced the immune response and coordinated vaccine-mediated immune response by suppressing genes associated with excessive inflammatory responses, such as nuclear factor kappa B, via Sirtuin 1 expression. Our findings elucidated the immunological mechanisms induced by D-galacto-D-mannan, suggesting a background for the robust cellular and humoral immune responses induced by FMD vaccines containing D-galacto-D-mannan. Our study will help to facilitate the improvement of conventional FMD vaccines and the design of next-generation FMD vaccines.

Interferon alpha 2b or Mitomycin-C as Adjuvant Therapy of Pigmented Conjunctival Malignancy : A Literature Review

Abstract
 Introduction & Objectives : To compare the efficacy and safety between Mitomycin C (MMC) and Interferon alpha-2b (IFN-α2b) eye drops as adjuvant therapy for conjunctival melanoma.
 Methods : Literature searching was conducted using PubMed, ScienceDirect, and Google Scholar. All studies that met the inclusion and exclusion criteria were categorized based on the level of evidence. The data of patients demographics, staging of disease, type of treatments, and outcomes of this review including local control rate, side effect, and recurrence and/or metastases were also reported.
 Results : From twelve articles, topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable complete remission rate. Local control (complete remission) of IFN α-2b group is 46%, while in MMC group is 57%. The most side effect of MMC group were severe corneal-conjunctival irritation and corneal defect, while the IFN α-2b group showed mild side effect. Recurrency rate of IFN α-2b group and MMC group both is 35%. Metastases case of IFN α-2b group is 3.8%, while none of cases from MMC group metastases.
 Conclusion : Topical adjuvant chemotherapy with MMC and IFN α-2b showed favourable local control rate even though the recurrency rate also relatively high. Both medications showed promising results to reduce residual tumor size after wide excision surgery, preserving eye so reduce the chance of exenteration in various stages. It is important to consider adjuvant therapy following wide excision surgery as the first line treatment.

Understanding Ocular Surface Disease in Glaucoma: A Comparative Analysis of Symptoms and Objective Parameters.

Background Glaucoma is a progressive optic neuropathy that may result in irreversible visual impairment and can diminish quality of life. Lowering intraocular pressure (IOP) through topical eyedrops is usually the primary approach to managing glaucoma. However, long-term treatment poses a risk to ocular surface health, leading to ocular surface disease (OSD). Preservative-containing eyedrops are implicated in OSD development due to their detrimental effects on the tear film and goblet cell density. OSD symptoms may impact patient compliance due to local side effects. This study aims to assess OSD in glaucoma patients receiving topical treatment, quantify symptoms and objective ocular surface parameters, and compare them to a control group not using topical glaucoma medications. Methodology Patients diagnosed with primary open-angle glaucoma receiving topical treatment and a control group were included in this study. To assess OSD, patients completed the Ocular Surface Disease Index (OSDI) questionnaire to evaluate symptoms and underwent objective measurements of ocular surface parameters using a keratograph. These parameters included assessments of bulbar redness and non-invasive keratograph tear break-up time (NIKTBUT). Results A cohort of 92 patients was subjected to examination, comprising 66 individuals diagnosed with glaucoma and 26 controls. Within the glaucoma patient subset, the mean number of IOP-lowering drugs administered was 2.42 ± 0.18, with 22.7% exclusively utilizing preservative-free eye drops. Our investigations unveiled a substantial prevalence of OSD symptoms, manifesting not only within the glaucoma cohort but also among the control group, with 72.7% and 53.8%, respectively (p = 0.224), reporting moderate-to-severe symptoms (OSDI > 23). Remarkably, OSDI scores exhibited higher values among female participants (p = 0.039) and glaucoma patients using prostaglandins (p<0.001) and were negatively correlated to the number of IOP-lowering drugs used (-0.448; p < 0.001). Furthermore, employing keratograph assessment, we discerned heightened bulbar redness (1.86 ± 0.07) in the glaucoma group compared to the control group (1.58 ± 0.07; p = 0.008). Glaucoma subgroup analyses further unveiled higher bulbar redness among glaucoma patients employing carbonic anhydrase inhibitors (p = 0.035) and applying medication preservatives (p = 0.045) but lower among individuals using beta-blockers (p = 0.018). However, the NIKTBUT did not show significant variance between the two groups (glaucoma group: 10.19 ± 0.85 seconds; control group: 10.96 ± 1.37 seconds; p = 0.499). Conclusions Our study revealed a significant prevalence of OSD in our sample, with the OSDI questionnaire showing limited specificity. The notable increase in bulbar redness pointed to an elevated prevalence of OSD among glaucoma patients, emphasizing the considerable impact of preservatives on ocular surface damage. Recognizing the potential damage to the tear film and ocular surface is crucial for glaucoma experts, who must employ comprehensive therapeutic strategies to mitigate symptoms, advocating for the preferential use of preservative-free medications, when possible, for optimizing long-term treatment.

Artículo traducido] Uso de rellenos faciales en la práctica clínica: nivel de satisfacción del paciente y visión general de las complicaciones clínicas comunes

BackgroundPatient esthetic satisfaction following facial fillers is an essential topic that should be studied as the number of individuals seeking treatment increases. The face is an essential component of the human body that is frequently associated with beauty, youthfulness, and health. Individuals may seek facial augmentation with fillers for a variety of reasons, such as congenital, acquired by means of aging or disease, or current aesthetic trends. ObjectiveThe aim is to assess patient's aesthetic satisfaction and description of common clinical complications in relation to the facial filler injections. MethodA cross sectional survey using a questionnaire derived from the global aesthetic improvement scale and WHO quality of life scale, convenience sampling was used to recruit patients attending cosmetic clinics, descriptive analysis and Chi-square methods were used to analyze the data. ResultsIn the study, 500 female participants, with an average age of 28.48 years, were included. Over 90% reported improvement after filler treatment, ranging from improved to very much improved. A statistically significant correlation was observed between patient satisfaction and the number of filler treatments and the anatomical injection site. However, no statistically significant correlation was found when considering age groups. Local side effects, such as swelling and redness at the injection site, were common but generally mild and of short duration. ConclusionAlthough the satisfaction level is currently high, practitioners in the field need to pay more attention to this important outcome, since understanding the patient's motivation and expectation before proceeding with the procedure is very important and can contribute significantly in determining patient satisfaction with the result.

The updated role of budesonide in managing children and adolescents with allergic rhinitis.

Allergic rhinitis (AR) is a prevalent disease in childhood and adolescence. A type 2 inflammation characterizes AR and, mainly, sustains nasal obstruction. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS) available since the early 1980s. BANS is indicated for treating allergic rhinitis. There is evidence about its efficacy in treating children and adolescents with seasonal and perennial AR. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with AR recommend the use of INCS as first line in many situations. In particular, AR patients (and their parents) may assess the perception of symptoms' severity using the Visual Analog Scale (VAS). A score ≥5/10 means uncontrolled symptoms and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In conclusion, BANS represents a valuable option in managing children and adolescents with AR.

Budenoside aqueous nasal spray: an updated reappraisal in rhinitis management.

Allergic rhinitis (AR) and nonallergic rhinitis are prevalent diseases. In western countries, type 2 inflammation usually characterizes these medical conditions and mainly sustains nasal obstruction. Budesonide aqueous nasal spray (BANS) is an intranasal corticosteroid (INCS) that has been available since the early 1980s. BANS is indicated for treating allergic rhinitis, nonallergic rhinitis, and nasal polyps (both as treatment and prevention after surgery). Consolidated evidence confirms its efficacy in treating seasonal and perennial AR, and nonallergic rhinitis. In addition, BANS is safe with negligible local and systemic side effects. Recent guidelines for patients with AR 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. A score ≥5/10 means uncontrolled symptoms and requires adequate treatment. BANS could appropriately be used in patients with uncontrolled symptoms and/or moderate/severe nasal obstruction. In conclusion, BANS represents a valuable option in managing patients with type 2 inflammation of the nose.

Side Effect Profile of Meningococcal B Vaccine in Children

Objective: Invasive meningococcal infections have a clinical picture with a rapid onset and can lead to serious sequelae and death even in individuals who are treated early. The most common causes of related epidemics are serogroups A, B, C, W, Y, and X, and two different vaccines have been developed against serogroups A, C, W, and Y and serogroup B. The serogroup B-containing MenB-4C vaccine (Bexsero®) was licensed in Turkey in 2018 and is still being administered. In this study, the side effects of this vaccine in infants and children followed up in a tertiary pediatric clinic were questioned. Materials and Methods: In our study, the local and systemic side effects of the MenB-4C vaccine doses, which were administered between March 1, 2019, and March 1, 2022, at the Child Health Follow-up Outpatient Clinic of Gazi University Faculty of Medicine, were evaluated retrospectively. All infants and children aged 0-18 years who were vaccinated at this clinic on the specified dates (n = 102) were recruited, and a questionnaire was completed by calling their parents by telephone and questioning the side effects of the vaccine. Results: It was determined that a total of 224 doses of the MenB-4C vaccine were administered to 102 children over the three-year study period, Of these vaccines, 21.6% were administered during the year before the pandemic and 78.4% during the two years after the pandemic. According to the total number of doses, the rate of local and systemic side effects was 30.8% (n= 69). It was found that among the 69 doses with side effects, 42 (60.8%) were systemic (fever), and 27 (39.1%) were local (stiffness, redness, and pain at the injection site). Side effects were observed in 41.3% of the patients after the first dose of the vaccine, 23.3% after the second dose, and 25.9% after the third dose. Conclusion: In our study, no serious post-vaccine reactions, such as anaphylaxis and encephalopathy, were observed following vaccination with MenB-4C, and the most common side effects of this vaccine were fever and local pain, which were only transient and self-limiting, lasting only two to three days at most. Since the MenB-4C vaccine, which has been included in the vaccination schedule of most countries, is a strong tool to help prevent meningococcal infections, every parent presenting to a health institution should be informed by the physician about the necessity of this vaccine, and if possible, conjugated meningococcal vaccines containing not only serogroups A, C, W, and Y but also serogroup B should be added to the national vaccine scheme.

Outcome of 6 Cycles of Primary Intravenous Chemotherapy of Retinoblastoma Patients in Terms of Recurrence in a Tertiary Health Care Hospital

Objective: To determine the frequency of recurrence after 6 cycles of primary intravenous chemotherapy of retinoblastoma patients in a tertiary health care hospital.&#x0D; Materials and Methods: This study was conducted at the Department of Ophthalmology, Lahore General Hospital, Lahore from March 15, 2020 to September 15, 2020. A total of 81 patients were selected randomly from outpatient department. Performa designed was used to collect data including name, age, gender, registration number, laterality, age at diagnosis, group of disease, treatment given and outcomes of given treatment. International Intraocular Retinoblastoma Classification (IIRC) was used for classification of the disease. The chemotherapy regimen used was vincristine, etoposide and carboplatin (VEC). A total of 6 cycles were given at 3 weekly intervals. Serial monitoring of the tumors was done to rule out any local recurrence or side effects of therapy.&#x0D; Results: Total 81 children presenting with retinoblastoma were enrolled in this study. There were 52(64.2%) male and 29(35.8%) female. The mean age of patients was 3.41±1.45 year. Unilateral disease was in 61 (75.30%) patients while 20 (24.70%) patients had bilateral retinoblastoma. Among 81 children, 20(24.7%) had recurrence of the disease.&#x0D; Conclusion: Development of recurrence after intravenous chemotherapy was noted in 24.7 % of all retinoblastoma eyes. Younger patients with more advanced, posteriorly located tumors and subretinal seeds at presentation were at increased risk, but recurrence can often be managed with globe-sparing therapy.

The impact of corona virus disease-2019 (COVID-19) vaccination on patients with systemic rheumatic diseases attending a tertiary care university-based hospital

BackgroundSafety and efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine among systemic rheumatic diseases (SRDs) remain a serious concern. Aim of the workTo explore different corona virus disease-2019 (COVID-19) vaccine adverse reactions, post-vaccination COVID-19 infection, disease flare and acceptability of vaccine among patients with SRDs. Patients and methodsThis study was conducted on 750 patients with SRDs attending the Rheumatology Department, Cairo University Hospitals (December 2022 – February 2023). All patients were subjected to full clinical history, COVID-19 infection, vaccine history, adverse events, disease flare and assessment of their acceptability to the vaccine. ResultsThe mean age of the patients was 41.6 ± 11.7 years with a female:male 8.4:1 and 52.5 % were educated. 414 (55.2 %) received COVID-19 vaccine. Only 26 (6.3 %) suffered from post-vaccination COVID- 19 infection (one mild attack). The causes for not receiving the vaccine were either due to unacceptability (78.9 %) or doctors’ advice (21.1 %). 64.8 % received inactivated virus vaccines (64.8 %) and 87.9 % received two doses. The commonest local and systemic side effects were pain (73.9 %) and headache (30.2 %). Only four (0.96 %) patients reported disease flare. There was a significant difference between the diagnosis, type of vaccines and some of the adverse effects of the vaccines such as pain (p = 0.019) and fever (p = 0.021), redness (p = 0.007) and swelling (p = 0.013). ConclusionThe efficacy and safety of SARS-CoV-2 vaccine among Egyptian patients with SRDs is confirmed. There were significant differences in certain vaccine side effects especially pain, fever, redness and swelling. Most patients well tolerated the COVID-19 vaccine providing reassurance.

Краткая история адреномиметиков и улучшенные комбинации в лечении заболеваний верхних дыхательных путей

One of the important components in the treatment of inflammatory diseases of the upper respiratory tract is the use of topical adrenomimetics, the irrational use of which leads to the development of local and systemic side effects. To minimize the negative effects, it is necessary to use modern vasoconstrictive drugs that have a complex effect due to the addition of medicines to their composition that improve mucociliary clearance, moisturize the mucous membrane of the nasal cavity and paranasal, regeneration processes. The aim of the work was to study the possibility of effective use of a decongestant with alpha-adrenomimetic activity xylometazoline in combination with sodium hyaluronate. The material for the study was a review of the literature on the use of vasoconstrictors in practical otorhinolaryngology for the period 2003–2023, in domestic specialized publications eLibrary, and scientific databases Scopus, Web of Science, Medline. A brief review of the research methods described by the authors as well as the results of drug therapy was conducted. As a result of the study, it was revealed that in the daily practice of an otorhinolaryngologist local short-acting decongestants are frequently prescribed drugs. They are used during diagnostic procedures, for therapeutic purposes, and, if used irrationally, can cause local and systemic side effects. Conclusion. To a greater extent, side effects are inherent in short-acting drugs; prolonged decongestants should be used, and it is advisable to not exceed the duration of the recommended treatment courses; one of the ways to solve this issue is to add hyaluronic acid to the decongestant.

Biodegradable calcium carbonate carriers for the topical delivery of clobetasol propionate.

Inflammatory dermatoses represent a global problem with increasing prevalence and recurrence among the world population. Topical glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs in dermatology due to a wide range of their therapeutic actions, which, however, have numerous local and systemic side effects. Hence, there is a growing need to create new delivery systems for GCs, ensuring the drug localization in the pathological site, thus increasing the effectiveness of therapy and lowering the risk of side effects. Here, we propose a novel topical particulate formulation for the GC clobetasol propionate (CP), based on the use of porous calcium carbonate (CaCO3) carriers in the vaterite crystalline form. The designed carriers contain a substantially higher CP amount than conventional dosage forms used in clinics (4.5% w/w vs. 0.05% w/w) and displayed a good biocompatibility and effective cellular uptake when studied in fibroblasts in vitro. Hair follicles represent an important reservoir for the GC accumulation in skin and house the targets for its action. In this study, we demonstrated successful delivery of the CP-loaded carriers (CP-CaCO3) into the hair follicles of rats in vivo using optical coherent tomography (OCT). Importantly, the OCT monitoring revealed the gradual intrafollicular degradation of the carriers within 168 h with the most abundant follicle filling occurring within the first 48 h. Biodegradability makes the proposed system especially promising when searching for new CP formulations with improved safety and release profile. Our findings evidenced the great potential of the CaCO3 carriers in improving the dermal bioavailability of this poorly water-soluble GC.

Topical Insulin for Neurotrophic-Related Epithelial Defects: Where do We Stand? A Systematic Review.

To review the existing literature to evaluate the utility of insulin eye drops as a treatment for neurotrophic-related epithelial defects. A comprehensive literature search of Medline, Embase, and Web of Science and additional manual searches were conducted using relevant keywords. All articles published from January 2005 to January 2024 were examined. Studies on the use of topical insulin drops in neurotrophic epithelial defects were included. A total of 16 articles were found relevant to be discussed in the review. All included patients had neurotrophic-related epithelial defects ranging from 3.8 mm2 to 144 mm2. After treatment with topical insulin, most of the epithelial defects showed a complete epithelialization. Various concentrations and types of insulin were used. The studies also varied in the type of vehicle used in the preparation of insulin drops. Two randomized controlled trials demonstrated that topical insulin drops were more effective than conventional treatment with artificial tears or autologous serum. All included studies, except for two, reported the absence of local or systemic side effects. Topical insulin is a promising and effective (adjuvant) treatment for neurotrophic keratopathy. It facilitates the healing of neurotrophic epithelial defects and offers many advantages over the current treatment options; insulin is widely available and it is relatively inexpensive. Topical insulin drops do not affect systemic blood glucose levels and are well tolerated. However, further investigation is needed.

Regenerative medicine in pterygium surgery

Aims/Purpose: Pterygium is a frequently occurring eye condition that arises due to excessive cellular growth, resulting in the development of abnormal fibrovascular growth of the conjunctiva. Despite the improvement of surgical techniques, preventing postoperative recurrence continues to be a significant challenge. At present, pterygium excision using conjunctival autograft is the preferred surgical method, however there is no universally accepted technique to completely eliminate the risk of pterygium recurrence. Plasma rich in growth factors (PRGF) is an autologous blood product rich in proteins and growth factors which can be rapidly obtained from patient blood. Clinically, it is an affordable treatment with potentially broad spectrum of applications in ophthalmology especially in the treatment of complex corneal disorders. The aim of this study was to evaluate the efficiency of autologous platelet‐rich plasma in the treatment of advanced pterygium and to compare it to conjunctival autograft technique.Methods: A total of 26 patients (31 eyes) with advanced pterygium were included in this study. Mean BCVA was 0.7. Patients were divided into 2 groups according to the surgical technique used: PRGF group (16 eyes) and conjunctival autograft group (15 eyes). All patients underwent excision of pterygium followed by closure of the bare sclera either by PRGF or conjunctival autograft. Solid PRGF was either just placed on the corneal surface or sutured with 2 nodes of 10–00 nylon suture at conjunctiva. If necessary, the procedure was repeated. All patients had corneal OCT scan and photo before the treatment and during the follow up. Patients were followed at 2, 6, 12 and 18 months after the procedure.Results: The mean surgery time was shorter in PRGF group (15.0 ± 2 min) compared to conjunctival autograft group (35.0 ± 5 min) (p = 0.001). Mean BCVA improved to 0.8 in both groups. The recurrence was observed in 2 eyes of conjunctival autograft group, while none of the eyes showed recurrence in PRGF group. Graft loss was observed in 2 cases in PRGF group and in 1 eye in conjunctival autograft group. None of the patients reported general or local side effects of the treatment.Conclusions: PRGF is a simple, fast, reliable and effective therapeutic tool to promote wound healing and prevent recurrence after advance pterygium excision.

Improving Inhalation Performance with Particle Agglomeration via Combining Mechanical Dry Coating and Ultrasonic Vibration.

Agglomerate formulations for dry powder inhalation (DPI) formed with fine particles are versatile means for the highly efficient delivery of budesonide. However, uncontrolled agglomeration induces high deposition in the upper airway, causing local side effects due to high mechanical strength, worse deagglomeration, and poor fine-particle delivery. In the present study, fine lactose was mechanically dry-coated prior to particle agglomeration, and the agglomerates were then spheroidized via ultrasonic vibration to improve their aerosol performance. The results showed that the agglomerate produced with the surface-enriched hydrophobic magnesium stearate and ultrasonic vibration demonstrated improved aerosolization properties, benefiting from their lower mechanical strength, less interactive cohesive force, and improved fine powder dispersion behavior. After dispersion utilizing a Turbuhaler® with a pharmaceutical cascade impactor test, a fine particle fraction (FPF) of 71.1 ± 1.3% and an artificial throat deposition of 19.3 ± 0.4% were achieved, suggesting the potential to improve the therapeutic outcomes of budesonide with less localized infections of the mouth and pharynx.

COVID-19 aşısına bağlı yan etkiler; faydalar risklerden ağır basıyor mu?

COVID-19 vaccine-associated adverse effects; benefits outweigh the risks?&#x0D; &#x0D; COVID-19 vaccine-associated adverse effects&#x0D; &#x0D; COVID-19 vaccines are vaccines produced with the latest technology in a very short time to get rid of this disease. These vaccines have been produced and used in millions around the world. Although some simple local side effects have been reported during and immediately after the administration of the vaccine, long-term side effects affecting various organs have recently been begun to be reported, especially with the use of mRNA vaccines. This minireview discusses the issues related to these simple and less common side effects.

The Use of rAAV2-RB1-Mediated Gene Therapy in Retinoblastoma.

Retinoblastoma (RB) is a life-threatening malignancy that arises from the retina and is activated upon homozygous inactivation of the tumor suppressor RB1. Gene therapy targeting RB1 is an effective strategy to treat RB. However, it is difficult to target the RB1 gene by site-specific repair, with up to 3366 gene mutation sites identified in RB1. Thus, it is necessary to construct a promising and efficacious gene therapeutic strategy for patients with RB. To recover the function of the RB1 protein, we constructed a recombinant adeno-associated virus 2 (rAAV2) expressing RB1 that can restore RB1 function and significantly inhibit RB progression. To confirm the clinical feasibility of rAAV2-RB1, the RB1 protein was validated in vitro and in vivo after transfection. To further evaluate the clinical efficacy, RB patient-derived xenograft models were established and applied. The biosafety of rAAV2-RB1 was also validated in immunocompetent mice. rAAV2-RB1 was a rAAV2 expressing the RB1 protein, which was validated in vitro and in vivo. In vitro, rAAV2-RB1 was effectively expressed in patient-derived RB cells. In mice, intravitreal administration of rAAV2-RB1 in a population-based patient-derived xenograft trial induced limited tumor growth. Moreover, after transfection of rAAV2-RB1 in immunocompetent mice, rAAV2-RB1 did not replicate and was expressed in other important organs, except retinas, inducing minor local side effects. Our study suggested a promising efficacy gene therapeutic strategy, which might provide a chemotherapy-independent treatment option for RB.

Women's Preferences for Hypofractionated Radiation Therapy for Treatment of Early-Stage Breast Cancer: A Discrete Choice Experiment

IntroductionThe primary treatment recommended for early-stage breast cancer is breast conserving surgery followed by external beam radiation therapy of the whole breast. Previously radiation therapy for early-stage breast cancer was given using more fractions over longer durations. Guidelines support treatments with fewer fractions over a shorter time (hypofractionated radiation therapy-HFRT). This study aimed to understand women's preferences for different features of treatments for early-stage breast cancer. MethodsA discrete choice experiment (DCE) with 12 choice tasks was conducted, describing the treatments by: extent of surgery, duration of radiation treatment, need to relocate for treatment, local side effects, changes in breast appearance, costs, and difficulty with daily activities during and after treatment. Participants were women with breast cancer and from the general population. Mixed logit analyses were conducted and trade-offs between attributes estimated. Results420 respondents completed the DCE. The relative importance of attributes varied by respondent characteristics; the most influential attribute for younger women was type of surgery (breast conserving surgery); type of surgery did not influence older women's preferences. Shorter treatment duration, avoiding relocation, fewer local side effects, and less difficulty with daily activities all positively influenced treatment preference. Younger women were willing to accept 32-40 days of radiation treatment before a treatment that included mastectomy was potentially acceptable. Conclusionattributes of treatment such as duration, need for relocation, side effects and impacts on normal daily activities during and after treatment significantly influenced women's preference for treatment, including surgery. Our findings have the potential for real impact for patients and services including supporting one on one clinical discussions, supporting program and patient resource development, and by informing service funding, organisation and delivery.

Local and Systemic side effects of COVID-19 Vaccines

&lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;strong&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;Background:&lt;/span&gt;&lt;/strong&gt;&lt;/p&gt; &lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;To increase the public's acceptance of the vaccine, knowledge of its side effects is crucial. Thus, the purpose of this study was to identify side effects in the Saudi population following vaccinations with Pfizer BioNTech and AstraZeneca.&lt;strong&gt; &lt;/strong&gt;&lt;/span&gt;&lt;/p&gt; &lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;strong&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;Method:&lt;/span&gt;&lt;/strong&gt;&lt;/p&gt; &lt;p class="MsoNormal"&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;In Saudi Arabia, an online survey was conducted between March and October of 2021. Participants from Saudi Arabia who received two doses of the Pfizer BioNTech or AstraZeneca vaccine took part. The survey identified side effects following vaccinations. &lt;/span&gt;&lt;/p&gt; &lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;strong&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;Results: &lt;/span&gt;&lt;/strong&gt;&lt;/p&gt; &lt;p class="MsoNormal"&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;AstraZeneca and Pfizer BioNTech administered vaccines to 174 and 224 of the 398 subjects, respectively. Fatigue (83.9%), local pain (78.2%), bone or joint pain (74.1%), fever (67.8%), vomiting or loss of appetite (24.1%), swelling (24.1%), and redness (21.8%) were the most commonly reported side effects for participants who took AstraZeneca.&lt;span style="mso-spacerun: yes;"&gt;&amp;nbsp; &lt;/span&gt;&lt;/span&gt;&lt;/p&gt; &lt;p class="MsoNormal"&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi;"&gt;For the participants who received Pfizer BioNTech, the most common adverse effects that were reported were fatigue (43.8%), bone or joint pain (38.4%), swelling (28.6%), fever (22.8%), redness (15.1%), and nausea or vomiting (11.2%). Local pain accounted for 90.6% of the adverse effects that participants reported. &lt;/span&gt;&lt;/p&gt; &lt;p class="MsoNormal" style="text-align: justify;"&gt;&lt;strong&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; color: black;"&gt;Conclusions:&lt;/span&gt;&lt;/strong&gt;&lt;/p&gt; &lt;p class="MsoNormal"&gt;&lt;span style="font-size: 10.0pt; font-family: 'Arial',sans-serif; mso-ascii-theme-font: minor-bidi; mso-hansi-theme-font: minor-bidi; mso-bidi-theme-font: minor-bidi; color: black;"&gt;After receiving the COVID-19 vaccine, the majority of participants reported experiencing at least one side effect. Whereas the AstraZeneca vaccination was linked to a higher prevalence of systemic side effects, the Pfizer BioNTech vaccination was linked to a higher prevalence of local adverse effects. Most adverse events following vaccination are not fatal. After receiving an AstraZeneca or Pfizer BioNTech vaccination, side effects were more common in women and younger age groups. Vaccinations against coronavirus have a good safety record.&lt;/span&gt;&lt;/p&gt;

Impact of SARS-CoV-2 Infection on Humoral and Cellular Immunity in a Cohort of Vaccinated Solid Organ Transplant Recipients.

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.