Fourth Injection Research Articles

Pharmacokinetics, Pharmacodynamics, and Safety of Intravenous Efgartigimod and Subcutaneous Efgartigimod PH20 in Healthy Chinese Participants.

Efgartigimod, a human immunoglobulin G (IgG)1-derived Fc fragment targeting the neonatal Fc receptor, has been developed into intravenous (IV) and subcutaneous (SC) formulations for treating generalized myasthenia gravis (gMG) and other autoimmune diseases. Data in the Chinese population were not available to date, and while both formulations have been approved in the USA, the EU, Japan and Chinafor the treatment of gMG. We present the pharmacokinetic, pharmacodynamic, and safety of IV and SC PH20 efgartigimod in healthy Chinese participants. In two independent, double-blinded, placebo-controlled, phase I studies of the IV and SC formulations of efgartigimod, healthy Chinese adults were randomized 3:1 to receive active treatment or matching placebo once every 7 days for four doses. Primary endpoints were pharmacokinetic parameters. After the fourth IV infusion, a mean maximum observed concentration (Cmax) of 194 µg/mL was reached at the end of the 1 h infusion; the mean area under concentration-time curve from time zero to 168 h (AUC0-168h) was 5300 µg × h/mL. After the fourth SC injection, a mean Cmax of 42.1 µg/mL was achieved with a median Tmax of 47.74 h; the mean AUC0-168h was 4790 µg × h/mL. Maximal mean reductions from baseline in total IgG levels were reached approximately 24 days after the first dose (60.7%, IV formulation; 66.4%, SC formulation). Treatment-related adverse events (TRAEs) were reported in seven (58.3%) participants receiving SC efgartigimod, mostly injection-site reactions. No TRAEs or AEs of special interest were reported in the IV study. The efgartigimod IV and SC pharmacokinetic, pharmacodynamic, and safety profiles in Chinese participants were similar to the known profiles in non-Chinese participants. Both formulations effectively reduced total IgG levels by a similar percentage. CTR20211952 and CTR20211805.

Platelet rich plasma injection in knee osteoarthritis: results after four years.

Background Knee osteoarthritis (KOA) is a progressive degenerative disease and a leading cause of disability worldwide. Intra-articular injection of platelet-rich plasma (PRP) is still a debatable symptomatic treatment and has provided multiple publications in literature with mixed results. Aim of the work To evaluate the short and long term effects of intra-articular injection of PRP on pain and functional status of the knee joint as measured by the Lysholm questionnaire and visual analogic pain scale (VAS). Patients and methods Twenty-one patients with primary Kellgren-Lawrence grade 3 KOA were assessed using the Lysholm questionnaire and the visual analogue scale for pain (VAS). A single PRP injection was administered, followed by reassessment of VAS at the first, fourth and eighth weeks after the injection. After eight weeks, patients were assessed with VAS and Lysholm questionnaire. In order to evaluate the long term effect of this single injection, we reassessed the patients four years after the injection using the same method. Results Fifteen females (71%) and six males (29%) with mean age 60 years (ranging from 44 to 76 years) were enrolled. After a single PRP injection, there was significant improvement in Lysholm and VAS. Before the injection, VAS medium score was 7 (ranging from 5 to 9) and we observed improvements in all assessments at the first (medium VAS 2), fourth (medium VAS 2) and eighth week (medium VAS 2) post injection and was still better than the pre injection score after 4 years (medium VAS 4). This was also observed in Lysholm score. The pre injection score was 41; at 8 weeks, 84; at 4 years, 66. Conclusion PRP injection achieves good results in the symptomatic treatment of Kellgren-Lawrence grade 3 KOA. This study confirmed that a single PRP injection can provide a long-term effect in pain reduction and functional status improvement in KOA, despite the progression of the disease. Further studies with more patients and randomized double blinded controlled studies are recommended to confirm these results.

Two-year Outcomes of Intravitreal Aflibercept Injection for Neovascular Age-related Macular Degeneration with "Observe before Treat-and-Extend" Method.

To evaluate 2-year outcomes of intravitreal aflibercept injection for neovascular age-related macular degeneration (nAMD) treated with "observe before treat-and-extend (O-TAE)" strategy in the real-world setting. This retrospective study included treatment-naive nAMD patients treated with aflibercept using O-TAE regimen and followed up for more than 2 years. Patients were observed bimonthly to check recurrence after three monthly loading injections. In case of recurrence, treatment was resumed using the TAE regimen starting from the fourth injection. In case of nonrecurrence, observation was continued. Best-corrected visual acuity (BCVA), central macular thickness (CMT), number of injections, TAE intervals, and proportion of recurrence after dry-up following three loadings were analyzed. A total of 38 eyes of 34 patients were included. Follow-up period was 37.0 ± 11.0 months. BCVA by logarithm of minimal angle of resolution improved from 0.33 ± 0.29 at baseline to 0.24 ± 0.23 in the first year (p = 0.010) and 0.25 ± 0.22 in the second year (p = 0.054). CMT decreased significantly from 357.43 ± 74.53 μm at baseline to 269.62 ± 48.12 μm in the first year (p < 0.001) and 279.14 ± 54.64 μm in the second year (p < 0.001). Number of injections were 5.11 ± 1.69 in the first year and 3.84 ± 2.39 in the second year. The percentage of eyes with a TAE interval of ≥12 weeks was 37.0% in the first year and 34.4% in the second year. Of the 36 eyes that dried up after three loadings, 28 eyes (77.8%) recurred, and the average period of recurrence was 6.5 months. The remaining eight eyes (22.2%) had no recurrence during the mean follow-up period of 29.7 months. This study showed that the newly suggested O-TAE strategy can reduce the treatment burden significantly reducing the number of injections while improving BCVA and CMT in the first and second year.

Changes in Macular Pigment Optical Density after Intravitreal Faricimab in Neovascular Age-Related Macular Degeneration: A Pilot Study.

Background: This study aimed to evaluate the effects of faricimab intravitreal injections in patients with exudative age macular degeneration (nAMD) after the loading dose using spectral domain optical coherence tomography (SD-OCT) and macular pigment optical density (MPOD). Methods: In this observational prospective study, we enlisted a total of 12 consecutive eyes of 12 patients (six females, six males; mean age 70.47 ± 2.46 years) affected by nAMD who consecutively presented to the Eye Clinic of the University of Naples "Federico II" and Monaldi Hospital of Naples, from June 2023 to December 2023. All patients received four once-monthly intravitreal injections of faricimab (6 mg/0.05 mL) (loading phase). At baseline and 1 month after the fourth faricimab monthly injection, all patients underwent assessment of best correct visual acuity (BCVA) and ophthalmic examination, including slit-lamp biomicroscopy, intraocular pressure (IOP), fundus biomicroscopy, SD-OCT, and MPOD. Results: A total of 12 eyes of 12 patients (six women, six men; mean age 70.47 ± 2.46 years) were included in this study. A statistically significant raise in BCVA and MOPD parameters was shown between baseline and after the loading phase (p < 0.001). Conclusions: Intravitreal injections of faricimab led in the short term to a significant functional and MPOD improvement along with a decrease in central macular thickness (CMT) and thus appears to be an effective treatment option without relevant adverse effects. MOPD may be considered as a prognostic factor associated with a good visual prognosis after intravitreal injections treatment.

Patient experiences switching from in-clinic to self-administration of injectable contraception in two Western US states.

We describe the experiences and preferences of women who switched from clinic-administered intramuscular depot medroxyprogesterone acetate (DMPA-IM) to self-administered subcutaneous DMPA (DMPA-SC) in the context of the COVID-19 pandemic. We conducted interviews with women in California and Washington about their experiences with self-administered DMPA-SC. We interviewed women after their first or second self-administered DMPA-SC injection and conducted follow-up interviews after their third or fourth injection. We performed both thematic and descriptive content analyses. We completed 29 interviews with 15 women. Most participants (n = 10) were between the ages of 20 and 39 and the majority (n = 12) used DMPA primarily for contraception. Most (n = 13) described self-administered DMPA-SC as "very easy" or "somewhat easy" to use and reported greater convenience, decreased pain, fewer logistical and financial challenges, increased privacy, and improved comfort with injection compared to DMPA-IM. Participants identified difficulties obtaining DMPA-SC from pharmacies and safe needle disposal as barriers. Most (n = 13) would recommend DMPA-SC to a friend and desired to continue self-administration beyond the COVID-19 pandemic. Participants recommended counseling all patients about this option alongside other contraceptive methods, and offering clinician supervision, if desired. Women who switched from in-clinic DMPA-IM to self-administered DMPA-SC during the COVID-19 pandemic preferred the latter and intended to continue self-administration. Self-administration of DMPA-SC should be routinely offered and easily accessible to patients.

O-012 Three Injections Protocol for IVF; a proof of concept study into elaborating the outmost patient friendly protocol in IVF

Abstract Study question To examine if 3 injections in follicular phase, with long-acting FSH, long-acting antagonist and HCG/Agonist triggering can result in efficient egg retrieval and blastocyst formation. Summary answer In this proof-of-concept study, all patients retrieved mature oocytes and ended having adequate blastocysts by receiving only 3 injections in the follicular phase. What is known already The old-fashioned way with multiple injections (majority minimum 15 injections) is still the golden IVF standard. Twenty years ago, a long-acting FSH gonadotropin brought into market (corifollitropin alpha) which represented a huge step in simplifying the follicular phase Recently, a new long-acting GnRH-antagonist emerged (degarelix) which can downregulate the hypophysis for 30 days. We have published that titrating this long-acting antagonist to 0,1mg single dose we can downregulate hypophysis without LH surge. Study design, size, duration A prospective proof of concept study included in total 15 patients 30-39 years old who followed IVF treatment with homologous oocytes during 2020-2022 in Assisting Nature IVF Clinic, Thessaloniki, Greece. In this study, we test if by delaying one day the long-FSH and also delaying the long-antagonist, still patients can produce mature eggs without needed extra FSH doses. Institutional review board approved the protocol. Participants/materials, setting, methods Patients were enrolled if AMH was 1,5-3,0 ng/ml and antagonist protocol applied. 150IU fixed corifollitropin-a (Elonva) for ovarian stimulation administered either on evening cycle Day-3 or morning day-4. Fixed 0,1 mg of long-acting GnRH-antagonist (Degarelix) administered on cycle Day 8. Fixed 250mcg recombinant-hCG (Ovitrelle) or 0,3 mg of Triptorelin (Arvekap) for ovulation triggering administered as soon as 3 follicles of 18mm were present. Produced blastocysts were all cryopreserved and transferred in subsequent thawed cycles. Main results and the role of chance All 15 patients reached ovum pick-up with mature eggs retrieved (mean 13,5 oocytes). None experienced any LH surge, however, 3/15 (20%) required an extra dose of 300IU FSH (Puregon) to enhance follicular development. The majority 12/15 reached OPU without any FSH adjuvant. All 15 patients had blastocysts formed (mean 3,3) and in their subsequent thawed cycles the cumulative live birth rate was 53,3% (8/15). Patient satisfaction was excellent though closer monitoring was applied due to novelty of the protocol. Limitations, reasons for caution Limited number of patients as it is a complete novel protocol with unknown outcome. Protocol was focused in normo-ovarian-reservers to secure follicular production. Some patients might need an extra dose of gonadotropin. Long-acting antagonist still not registered for IVF use. Wider implications of the findings Current study promising results indicate that a 3-injection follicular stimulation can efficiently produce mature eggs, viable blastocysts and pregnancies. Although, few patients required an extra fourth injection of FSH, if such approach will be tested in larger studies will re-establish our way for stimulation at least for normo-reservers. Trial registration number NCT03877185

The effect of intravitreal cidofovir injection on end-stage glaucoma in dogs: a retrospective study of 153 eyes.

To evaluate the long-term efficacy, prognostic factors, and complications of intravitreal cidofovir injection in dogs with end-stage glaucoma. 130 client-owned dogs. Medical records of dogs that underwent intravitreal cidofovir injections were reviewed. A minimum follow-up period of 6 months was required as the inclusion criterion. Signalment, type of glaucoma, preinjection intraocular pressure (IOP), types of applied glaucoma eye drop, coexisting ocular diseases, outcomes, and complications were recorded. Success was defined as IOP of ≤ 25 mm Hg at the 2-week recheck that remained to the 6-month recheck. The overall success rate of intravitreal cidofovir injection was 91.5% (140/153). The success rate of a single injection was 69.3% (106/153), of a second injection was 59.5% (25/42), of a third injection was 42.9% (6/14), of a fourth injection was 33.3% (2/6), and of a fifth injection was 50.0% (1/2). Intraocular pressures at 6 months after injection were relatively higher when the injection was repeated, fewer types of glaucoma eye drop were applied prior to the injection, and cataract stages were advanced at the time of injection (P < .05). The most common complications were phthisis bulbi (42.5%), cataract progression (30.1%), and intraocular hemorrhage (16.3%). Six eyes were enucleated, and 3 were enucleated due to corneal perforation. Intravitreal cidofovir injection had a high long-term success rate in lowering IOP in dogs with end-stage glaucoma.

A Pilot Study to Investigate Peripheral Low-Level Chronic LPS Injection as a Model of Neutrophil Activation in the Periphery and Brain in Mice.

Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the periphery and brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate its impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, was higher in LPS-injected mice compared to saline-injected mice after 4 weeks but not 8 weeks of injections. Neutrophil frequency and activation increased in the periphery 4-12 h and 4-8 h after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 h following the final injection. Neutrophil activation was increased in the brain of LPS-injected mice when compared to saline-injected mice 4-8 h after the final injection. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery-brain axis of inflammation with age and/or in mouse models of neurodegenerative or neuroinflammatory disease.

Increase of prostate-specific antigen doubling time predicts survival in metastatic castration-resistant prostate cancer patients undergoing radium therapy.

Radium-223 (Ra-223) is an important treatment modality for bone-dominant metastatic castration-resistant prostate cancer (mCRPC). However, there is currently a lack of effective markers to monitor treatment response during treatment. We aim to investigate the response in prostate-specific antigen doubling time (PSADT) as a potential marker for assessing Ra-223 treatment in mCRPC patients. We retrospectively collected data from mCRPC patients who underwent radium treatment at our institution between August 2020 and June 2023. Prostate-specific antigen (PSA) measurements prior to treatment and during treatment were collected. Baseline PSADT was calculated from PSA measurements prior to Ra-223 treatment; interim PSADT was calculated from PSA measurements before Ra-223 treatment and prior to the fourth course injection. Overall survival was calculated from the start of treatment to the date of death. Univariable and multivariable analysis using the Cox proportional hazards model were performed to examine the association of factors with overall survival. We included 35 patients from our institution, with a median overall survival of 13.3months. Eighteen (51.4%) completed all six courses of treatment. PSA dynamic response (interim PSADT > baseline PSADT or decreased PSA) was observed in 20 patients. Overall survival was associated with a PSA dynamic response (HR = 0.318, 95% CI 0.133-0.762, p = 0.010) when compared to patients without response. Dynamic changes in PSADT were associated with survival in mCRPC patients receiving radium therapy. Comparing interim and baseline PSADT could serve as a valuable marker for determining treatment benefits.

Treatment of Knee Osteoarthritis in a Military Cohort Using Platelet-Rich Plasma

Osteoarthritis is a devastating condition affecting an estimated 240 million people world-wide and is associated with significant morbidity and medical costs. Platelet-rich plasma has demonstrated success for the treatment of knee osteoarthritis with minimal adverse events. While US military service members experience osteoarthritis at a younger age and an increased frequency compared to nonmilitary populations, there is a paucity of research studies evaluating platelet-rich plasma in this high-risk population. This study is the first to evaluate the treatment response of US active-duty military and veterans receiving platelet-rich plasma injections for knee osteoarthritis. Using retrospective Knee Osteoarthritis Outcome Score (KOOS) data collected to evaluate the treatment response of platelet-rich plasma for knee osteoarthritis, we analyzed the data by age, sex, military rank, and number of injections for statistical significance. Despite a significant dropout rate during the study, we found 2 injections were superior to 1, 3, or 4 injections in reaching statistical significance for improvement in patient pain and function. Third and fourth injections saw a decrease in KOOS across all subcategories. Our data differed from non-military PRP studies which supports 3 injections provides the greatest improvement in pain and function. As a retrospective observational cohort study, we were unable to control for variables of treatment frequency and duration making it difficult to generalize our results to that of current literature. However, we did see a potential for additional platelet-rich plasma injections being superior with regards to improvement in pain and function. While there remains a scarcity of data within the military receiving platelet-rich plasma for knee osteoarthritis, future larger, prospective, double-blinded, randomized control trial studies could support platelet-rich plasma as an effective treatment option in this high-risk population.

Scleritis following intravitreal brolucizumab injection: a case series

BackgroundThis study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections.Case presentationCase 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon’s capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. Case 2. An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn’t due to progression of nAMD.ConclusionsIntraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

Ocular canine transmissible venereal tumour: Report of three cases

AbstractThis study investigated three cases of transmissible venereal tumour in dogs. In Case 1, a 5‐year‐old male dog presented with an eye mass and penile growths, unresponsive to previous treatment. Case 2 involved a 4.5‐year‐old male dog with bilateral ocular masses and penile lesions. Case 3 featured a stray dog with ocular and skin masses. All cases were confirmed as transmissible venereal tumour through impression smear cytology. Treatment with vincristine sulphate resulted in significant remission, with complete recovery after the fourth injection. This study contributes valuable knowledge for veterinarians in diagnosing and treating transmissible venereal tumour in dogs, emphasising the significance of an approach to case management and careful consideration of the varying clinical manifestations of the disease.

Comparison of Treatment Efficacy of Different Number of Botulinum Toxin Type A Injection Sites for Crow’s Feet Lines: A Single-Center Retrospective Clinical Study in Vietnam

Objective: Botulinum toxin type A is frequently used to treat crow’s feet lines. However, the optimal dose and injection sites are still controversial. The objective of this study was to compare the efficacy of different botulinum toxin type A injection patterns for the treatment of crow’s feet. Methods: This single-center, retrospective, clinical study was conducted at the National Hospital of Dermatology and Venereology from July 2020 to December 2020. Data on 60 patients with crow’s feet were collected and divided into 2 groups (3- or 4-point intramuscular injection) according to the intramuscular injection technique the patients received. The treatment efficacy was assessed based on the changes in the Crow’s Feet Grading Scale score at 1, 4, and 16 weeks after treatment. Repeated measures analysis of variance was used for the assessment of changes in scores over time between the two groups. Results: After treatment, the average Crow’s Feet Grading Scale score was significantly decreased compared with the pretreatment score at all timepoints (1, 4, and 16 weeks) in both states (dynamic: For 3-point intramuscular injection technique, 1 week: 1.90 ± 0.71 vs. 2.97 ± 0.56; 4 weeks: 1.87 ± 0.68 vs. 2.97 ± 0.56; 16 weeks: 2.60 ± 0.67 vs. 2.97 ± 0.56. For 4-point intramuscular injection technique, 1 week: 1.73 ± 0.83 vs. 3.03 ± 0.49; 4 weeks: 1.73 ± 0.74 vs. 3.03 ± 0.49; 16 weeks: 2.57 ± 0.68 vs. 3.03 ± 0.49, all P &lt; 0.001. and static: For 3-point intramuscular injection technique, 1 week: 1.20 ± 0.89 vs. 2.20 ± 0.85; 4 weeks:1.20 ± 0.89 vs. 2.20 ± 0.85; 16 weeks: 1.87 ± 0.97 vs. 2.20 ± 0.85; For 4-point intramuscular injection technique, 1 week: 1.50 ± 0.86 vs. 2.30 ± 0.84; 4 weeks: 1.33 ± 0.84 vs. 2.30 ± 0.84; 16 weeks: 1.87 ± 0.97 vs. 2.30 ± 0.84. All P &lt; 0.001). The average subjective patient-rated satisfaction scores after treatment were significantly higher in the 4-point injection group than in the 3-point injection group (P = 0.028). The adverse events were post-injection bruising in 3 patients and a feeling of eyelid tightness in 3 patients. Conclusion: Botulinum toxin type A injection is an effective treatment for crow’s feet. Adding a fourth injection maintains the same therapeutic effect and does not increase adverse effects. Patients with lower-fan crow’s feet patterns may benefit more from 4-point injection therapy. However, the present findings require confirmation in studies with larger sample sizes, longer follow-up times, and different botulinum toxin type A doses.

Admitting a patient with musculoskeletal pain following COVID-19 disease

A significant proportion of patients who have had COVID-19 continue to suffer from persistent symptoms such as severe weakness, shortness of breath, joint pain, mood swings and memory impairment during the recovery phase. More than half of the patients experienced joint pain for the first time after recovery from COVID-19. Three months after COVID-19 episode, joint pain continued to occur in more than a third of patients. We observed a 47-year-old patient with moderate shoulder pain that occurred for the first time after COVID-19. The examination also revealed changes in the hip joint. The diagnosis was made: post-COVID syndrome with reactive arthritis of the left shoulder joint, deforming osteoarthritis of the left hip joint stage I, degenerative-dystrophic changes in the lumbosacral spine, lower back pain. The therapy was prescribed – Chondroguard® intramuscularly every other day according to the following scheme: the first three injections (day 1, 3, and 5) 1 ml (100 mg), then, from the fourth injection (day 7) – 2 ml (200 mg) every other day, a course of 30 injections. Positive dynamics were achieved. No adverse events were noted during the treatment. The patient continued taking the nutraceutical Chondroguard® TRIO orally for 2 months. During the observational period, no adverse events were noted. Thus, in cases where post COVID-19 musculoskeletal pain is caused by joint involvement, chondroprotective therapy is effective: stage 1 – injections, stage 2 – oral therapy.

A case of hypertensive uveitis with intravitreal faricimab.

Purpose: To report a novel case of hypertensive uveitis with intravitreal faricimab. Methods: This is a case report. A 69-year-old female undergoing treatment of bilateral diabetic macular oedema with intravitreal faricimab presented for routine review. Ophthalmic examination was performed including visual acuity, intraocular pressure (IOP), gonioscopy, and slit lamp examination. Findings consistent with hypertensive uveitis prompted further infectious/inflammatory/infiltrative uveitis screen. Results: The patient developed hypertensive uveitis in the left eye (four weeks after the third injection) with an IOP of 42mmHg. Slit lamp examination revealed fine keratic precipitates and mild anterior uveitis. Anterior chamber angle was open on gonioscopy, and there was no vitritis or vasculitis. At review a week later, the patient had developed hypertensive uveitis in the right eye (six weeks after the fourth injection) with IOP of 35mmHg. Slit lamp examination revealed fine keratic precipitates, open angles, and mild vitritis. There was no vasculitis. At both presentations the patient had preserved visual acuity with no significant visual symptoms. The hypertensive uveitis resolved in both eyes with a course of steroid and antihypertensive eye drops. The uveitis screen was negative apart from elevated urine protein (negative beta-2 microglobulin) which could be explained by known diabetes and hypertension. Conclusion: Hypertensive uveitis is a potential adverse reaction to intravitreal faricimab. This case highlights the importance of monitoring intraocular pressure in patients undergoing treatment with faricimab and emphasises the need for reporting other cases in the community.

Fructose supplementation shifts rat brain metabolism in experimental migraine

AimsWe have previously demonstrated that fructose supplementation (FS), given in a scheme used for inducing metabolic syndrome (MS), elicited pain relief in the nitroglycerin (NTG)-elicited rat migraine model. Herein, we evaluated whether FS could reestablish the impaired metabolic pathways in NTG-injected rats. Main methodsMale Wistar rats (N = 40) were divided into two groups for receiving 10 % FS or tap water. After 45 days, they were subdivided into NTG-injected (10 mg/kg; 15 days) or controls. After the fourth NTG injection, 18F-fluorodeoxyglucose ([18F] FDG) micro-PET scanning was accomplished. The day after, euthanasia was performed, and blood was collected for glycemia and LDH analysis. The levels of energy molecules, TBARS, PGC-1α, and MCTS1 were evaluated in the brain cortices. The activated satellite glial cells (SGC) were assessed in the trigeminal ganglion (TG). Key findingsThere were no variations of glycemia or LDH serum levels. NTG-injected rats showed a significant increase in glucose uptake in the hypothalamus (HT) vs. NTG-free rats. The FS-NTG group showed increased metabolism in the superior colliculus (SC) vs. the NTG group. Moreover, the glucose uptake was amplified in the inferior colliculus (IC) of the FS-NTG vs. FS group. The cortical inosine levels were significantly higher in FS-NTG rats vs. NTG or FS groups, with no changes in TBARS or MCTS1 levels, despite a minor decrease of PGC1-α contents in the FS+NTG group. Finally, there was a significant increase of activated SGC around TG in the FS-NTG rats. SignificanceWe provide novel evidence linking nutrition and metabolism with migraine.

Safety and Effectiveness of Repeated Botulinum Toxin A Intracavernosal Injections in Men with Erectile Dysfunction Unresponsive to Approved Pharmacological Treatments: Real-World Observational Data.

Intracavernosal injections of botulinum toxin A (BTX/A ic) may be effective for difficult-to-treat erectile dysfunction (ED). This is a retrospective case series study of the effectiveness of repeated off-label BTX/A ic (onabotulinumtoxinA 100U, incobotulinumtoxinA 100U or abobotulinumtoxinA 500U) in men with ED and insufficient response to phosphodiesterase type 5 inhibitors (PDE5-Is) or prostaglandinE1 intracavernosal injections (PGE1 ICIs), defined as an International Index of Erectile Function-Erectile Function domain score (IIEF-EF) < 26 on treatment. Further injections were performed on patients' requests, and the files of men who underwent at least two injections were reviewed. The response to BTX/A ic was defined as the achievement of the minimally clinically important difference in IIEF-EF adjusted to the severity of ED on treatment at baseline. Out of 216 men treated with BTX/A ic and PDE5-Is or PGE1-ICIs, 92 (42.6%) requested at least a second injection. The median time since the preceding injection was 8.7 months. In total, 85, 44 and 23 men received, respectively, two, three and four BTX/A ic. The overall response rate was 77.5%: 85.7% in men with mild ED, 79% for moderate ED and 64.3% for severe ED on treatment. The response increased with repeated injections: 67.5%, 87.5% and 94.7%, respectively, after the second, third and fourth injections. Post-injection changes in IIEF-EF were similar across injections. The time from injection to request for a further injection varied little. Four men reported penile pain at the time of injection (1.5% of all injections), and one experienced a burn at the penile crus. Repeated BTX/A injections combined with PDE5-Is or PGE1-ICIs produced an effective and durable response, with acceptable safety.

Prognostic factors related to recurrence of trigger finger after open surgical release in adults

IntroductionRecurrent trigger finger after surgery is one of the major adverse events. However, studies to identify factors associated with recurrence after open surgical release in adult trigger finger patients are still limited. PurposeTo identify factors associated with recurrent trigger finger after open surgical release. MethodsThis 12-year retrospective observational study included 723 patients with 841 trigger fingers who underwent open A1 pulley release. Patients were categorized into 2 groups: those with recurrent trigger finger after surgery and those without. Associations between potential predictors including age, sex, duration of symptoms, occupation status, active smoker status, number of steroid injections before surgery, and types of comorbidities and the outcome of interest, recurrence of trigger finger, were examined using univariable and multivariable analyses. The results are presented as hazard ratios (HR) with a 95% confidence interval (95% CI). ResultsThe recurrence rate after trigger finger release was 2.39% (20 of 841 fingers). After adjusting for confounders, more than 3 steroid injections before surgery and manual labor were the independent predictors of recurrent trigger finger (HR = 4.87, 95%CI = 1.06–22.35 and HR = 3.43, 95%CI = 1.15–10.23, respectively). ConclusionsMore than 3 steroid injections before surgery and manual labor increase the risk of recurrent trigger finger after an open A1 pulley release. There may be limited benefit in administering a fourth steroid injection.

Dose Selection and Clinical Development of Efgartigimod PH20 Subcutaneous in Patients with Generalized Myasthenia Gravis (P1-5.017)

Dose Selection and Clinical Development of Efgartigimod PH20 Subcutaneous in Patients with Generalized Myasthenia Gravis (P1-5.017)

PENIS GROWTH RESPONSE TO HORMONAL THERAPY IN CHILDREN WITH MICROPENIS AT HASAN SADIKIN HOSPITAL

Objective: This study aims to determine the response of penis growth to testosterone injection. Material &amp; Methods: The study was conducted on all cases of micropenis from January 2016 to December 2020. Each subject who met the criteria for micropenis received 25 mg of intramuscular testosterone ester injection, in 4 doses with an interval of 1 week. Evaluation is done at the beginning, before administration of testosterone, then an evaluation is carried out for each patient before testosterone injection until 1 week after the 4th injection. Penis measurement is done by fully stretched length measurement. Results: There were 62 patients who met the criteria for micropenis. The average age of patients with micropenis when they first came was 5.9 years. The patient's mean initial penile length was 2.13 cm. There was an increase in penis length of 32% in the first injection, 28% after the second injection, 18% after the third injection and 14% after the fourth injection. The average length of the penis at the first, second, third and fourth injections was 2.53 cm, 3.24 cm, 3.65 cm and 4.01 cm, respectively. At the end of treatment, there was an average increase in penile length of 75.8% compared to the beginning of treatment. Conclusion: In conclusion, it can be said that testosterone therapy in micropenis patients gave a good response in terms of increasing penile length by 75.8% and increasing the average from 2.13 cm to 4.01 cm.