Human immunodeficiency virus infection challenges: Current therapeutic limitations and strategies for improved management through long-acting injectable formulation.

HIV infection has been a severe global health burden, with millions living with the virus and continuing new infections each year. Antiretroviral therapy can effectively suppress HIV replication but requires strict lifelong adherence to daily oral medication regimens, which presents a significant challenge. Long-acting formulations of antiretroviral drugs administered infrequently have emerged as a promising strategy to improve treatment outcomes and adherence to HIV therapy and prevention. Long-acting injectable (LAI) formulations are designed to gradually release drugs over extended periods of weeks or months following a single injection. Critical advantages of LAIs over conventional oral dosage forms include less frequent dosing requirements, enhanced patient privacy, reduced stigma associated with daily pill regimens, and optimised pharmacokinetic/pharmacodynamic profiles. Several LAI antiretroviral products have recently gained regulatory approval, such as the integrase strand transfer inhibitor cabotegravir for HIV preexposure prophylaxis and the Cabotegravir/Rilpivirine combination for HIV treatment. A leading approach for developing long-acting antiretroviral depots involves encapsulating drug compounds in polymeric microspheres composed of biocompatible, biodegradable materials like poly (lactic-co-glycolic acid). These injectable depot formulations enable high drug loading with customisable extended-release kinetics controlled by the polymeric matrix. Compared to daily oral therapies, LAI antiretroviral formulations leveraging biodegradable polymeric microspheres offer notable benefits, including prolonged therapeutic effects, reduced dosing frequency for improved adherence, and the potential to kerb the initial HIV transmission event. The present manuscript aims to review the pathogenesis of the virus and its progression and propose therapeutic targets and long-acting drug delivery strategies that hold substantial promise for enhancing outcomes in HIV treatment and prevention.

Key morphological features of human pyramidal neurons.

The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.

In situ CRISPR-Cas9 base editing for the development of genetically engineered mouse models of breast cancer.

Genetically engineered mouse models (GEMMs) of cancer have proven to be of great value for basic and translational research. Although CRISPR-based gene disruption offers a fast-track approach for perturbing gene function and circumvents certain limitations of standard GEMM development, it does not provide a flexible platform for recapitulating clinically relevant missense mutations in vivo. To this end, we generated knock-in mice with Cre-conditional expression of a cytidine base editor and tested their utility for precise somatic engineering of missense mutations in key cancer drivers. Upon intraductal delivery of sgRNA-encoding vectors, we could install point mutations with high efficiency in one or multiple endogenous genes in situ and assess the effect of defined allelic variants on mammary tumorigenesis. While the system also produces bystander insertions and deletions that can stochastically be selected for when targeting a tumor suppressor gene, we could effectively recapitulate oncogenic nonsense mutations. We successfully applied this system in a model of triple-negative breast cancer, providing the proof of concept for extending this flexible somatic base editing platform to other tissues and tumor types.

Impact of Surface Ligand on the Biocompatibility of InP/ZnS Quantum Dots with Platelets.

InP/ZnS quantum dots (QDs) have received a large focus in recent years as a safer alternative to heavy metal-based QDs. Given their intrinsic fluorescent imaging capabilities, these QDs can be potentially relevant for in vivo platelet imaging. The InP/ZnS QDs are synthesized and their biocompatibility investigated through the use of different phase transfer agents. Analysis of platelet function indicates that platelet-QD interaction can occur at all concentrations and for all QD permutations tested. However, as the QD concentration increases, platelet aggregation is induced by QDs alone independent of natural platelet agonists. This study helps to define a range of concentrations and coatings (thioglycolic acid and penicillamine) that are biocompatible with platelet function. With this information, the platelet-QD interaction can be identified using multiple methods. Fluorescent lifetime imaging microscopy (FLIM) and confocal studies have shown QDs localize on the surface of the platelet toward the center while showing evidence of energy transfer within the QD population. It is believed that these findings are an important stepping point for the development of fluorescent probes for platelet imaging.

Differences in Glycemic Control for Inpatients with Type 1 Diabetes on Insulin Pump Versus Subcutaneous Insulin Therapy.

BACKGROUND: Inpatient use of insulin pump therapy has been increasing due to greater availability of this technology, however there is a paucity of research that investigates glycemic control of inpatient insulin pump users. OBJECTIVE: To compare the glycemic control of hospitalized patients with type 1 diabetes (T1D) who used insulin pump vs. multiple daily injections (MDI). DESIGN: Retrospective chart review. PARTICIPANTS: Patients with T1D who were hospitalized between January 1, 2017, and December 31, 2019, in an academic medical center in the New York metropolitan area. MAIN MEASURES: Patients were categorized into three groups based on their method of insulin administration: "pump only" group used insulin pump exclusively, "MDI only" group used MDI only, and "intermittent pump" group used a combination of both methods. The primary endpoints are mean blood glucose, rates of hypoglycemic events (blood glucose < 70 mg/dL), and rates of hyperglycemic events (blood glucose > 250 mg/dL). Separate multivariable Poisson regressions were performed to determine the association between the type of insulin administration and rate outcomes (i.e., rate of hypoglycemic events and rate of hyperglycemic events). RESULTS: The study included 78 patients with a mean age of 51, who were mostly male (54%), and white (72%). The average proportion of glucose measurements that were hyperglycemic for the "pump only", "MDI only", and "intermittent pump" groups were 0.11 (SD = 0.11), 0.25 (SD = 0.19), and 0.24 (SD = 0.25), respectively. The "pump only" group has a significantly lower proportion of hyperglycemic events as compared to the "MDI only" group (p = 0.0227). CONCLUSIONS: In this sample, patients who exclusively used their insulin pump while inpatient had a lower rate of hyperglycemic events than patients who used MDI only; suggesting that select patients can safely continue their insulin pump therapy in the inpatient setting.

Is diabetic retinopathy screening worthwhile among people first diagnosed with diabetes at older ages? A cohort study of Norfolk diabetic retinopathy screening programme.

AIMS: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. METHODS: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. RESULTS: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70-79 and £26,214 in those aged 80-89. CONCLUSIONS: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable.

Botulinum toxin and conservative treatment strategies in people with cervical dystonia: an online survey.

Isolated cervical dystonia is a focal, idiopathic dystonia affecting the neck muscles. Treatment usually consists of botulinum neurotoxin (BoNT) injections into the dystonic muscles. Our aim is to investigate the use of BoNT treatment and conservative treatments by people living with cervical dystonia. An online survey in English was conducted between June and August 2022. Participants were eligible to participate if they were living with cervical dystonia, were over 18 years old and could read and understand English. The survey consisted of demographic questions, characteristics of dystonia, questions relating to BoNT use and the perceived utility of conservative treatments. The data were analysed descriptively, and open-ended questions were grouped into similar topics represented by direct quotes. We received 128 responses from people with cervical dystonia, with an average age of 59 years and 77% women. Most participants (52%) described their cervical dystonia as mild to moderate with an average pain score of 5/10. Eighty-two (64%) participants were having regular BoNT injections, with overall positive perceived effects. Common activities reported to improve the symptoms were the use of heat packs, massage, relaxation, physiotherapy and participation in general exercise. Common coping strategies reported were getting sufficient rest, having the support of friends and family, and remaining engaged in enjoyable hobbies. We found that most participants received regular BoNT injections and that heat packs, exercise, massage, physiotherapy and relaxation were mostly perceived as effective in reducing the symptoms of cervical dystonia.

Delineating patient errors in an intracavernosal injection program.

BACKGROUND: Intracavernosal injection therapy (ICI) is a well-established therapeutic strategy for men with erectile dysfunction. Complications are often related to patient error when performong ICI. AIM: The objective of this study was to examine patient errors in an established patient training program for performing ICI and identify factors that could predict major errors. METHODS: Patients enrolled in our ICI program are trained on technical aspects, and dose titration is begun. Patients are given explicit instructions during training, both verbally and in written form. Records were reviewed for men using ICI for ≥6 months. Multivariable analysis was used to define predictors of major errors. OUTCOMES: Errors were listed as minor (zero-response injection, penile bruising, expired medication) and major (errors potentially leading to priapism: dose self-titration, double injecting). RESULTS: Overall, 1368 patients met the inclusion criteria and were included in the analysis. The mean patient age was 66 ± 22 (range 29-91) years. Regarding education, 41% of patients had graduate-level education, 48% had college education, and 11% high school education. Mean follow-up was 3.2 ± 7.6 (range 0.5-12) years. The agents used were trimix (62%), bimix (35%), papaverine (2%), and prostaglandin E1 monotherapy (1%). At least 1 error occurred during self-administration in 42% of patients during their time in the program. Errors included zero response to medication due to technical error (8% of patients), penile bruising (34%), use of an expired bottle (18%), self-titration (5%), and double injecting (4% of patients); 12% of men committed ≥1 error during their time in the program. On multivariable analysis, independent predictors of the occurrence of a major error included: young age, graduate-level education, and <12 months of injection use. CLINICAL IMPLICATIONS: To the best of our knowledge, this is the first reported study to investigate ICI errors and risk factors. The identification of factors predictive of major errors allows for more tailored and intensive training in this subset of patients. STRENGTHS AND LIMITATIONS: Strengths of this study include a large patient population (1386 men) with a considerable follow-up time. Additionally, the rigorous training, education, and monitoring of the participants, as well as the use of formal definitions, enhances the accuracy and reliability of the results. Despite the strengths of the study, recall bias may be a limitation concern. CONCLUSION: The majority of patients were error free, and the majority of the errors were minor in nature. Major errors occurred in <10% of patients. Younger age, graduate-level education, and less experience with ICI were independent predictors of major errors.

Reticulated livedoid skin patterns after soft-tissue filler-related vascular adverse events.

BACKGROUND: For the treatment of vascular adverse events caused by filler injections, duplex ultrasound imaging may be used. The findings of duplex ultrasound examination and the clinical features of reticulated livedoid skin patterns were compared with the hemifaces anatomy. OBJECTIVE: The objective of this study was to link the reticulated livedoid skin patterns to the corresponding duplex ultrasound findings and the facial perforasomes. METHODS: Duplex ultrasound imaging was used for the diagnosis and treatment of vascular adverse events. The clinical features and duplex ultrasound findings of 125 patients were investigated. Six cadaver hemifaces were examined to compare the typical livedo skin patterns with the vasculature of the face. RESULTS: Clinically, the affected skin showed a similar reticulated pattern in each facial area corresponding with arterial anatomy and their perforators in the cadaver hemifaces. With duplex ultrasound, a disturbed microvascularization in the superficial fatty layer was visualized. After hyaluronidase injection, clinical improvement of the skin pattern was seen. Normalization of blood flow was noted accompanied by restoration of flow in the corresponding perforator artery. The skin patterns could be linked to the perforators of the superficial fat compartments. CONCLUSION: The livedo skin patterns seen in vascular adverse events may reflect the involvement of the perforators.

How to define failure of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity.

INTRODUCTION: Neurogenic detrusor overactivity (NDO) has a major impact on patients' quality of life and can lead to upper urinary tract complications. Intradetrusor botulinum toxin type A injections are administered as second-line treatment to these patients following the failure of anticholinergic agents. The aim of the DETOX 2 study is to propose a consensus definition of the failure of intradetrusor botulinum toxin injections for NDO in patients presenting spinal cord injury, spina bifida, or multiple sclerosis (MS) with self-catheterization. METHOD: This study followed the method adopted by the French National Authority for Health for recommendations by consensus. Based on a review of the literature and a preliminary survey, a steering committee compiled a questionnaire and selected a rating group comprising 16 experts from the Neuro-Urology Committee of the French Urology Association (cnuAFU) and Genulf. The experts were asked to complete the online questionnaire. At the end of the first round, all participants came together to discuss any disagreements and a second-round online questionnaire was completed to reach a consensus. RESULTS: Thirteen of the 16 experts approached completed both rounds of questionnaires. A strong consensus was reached for two proposals (median score = 9/10) which were therefore included in the definition from the first round: at least one repeat injection of the same botulinum toxin at the same dose must be given to rule out failure on technical grounds and a duration of efficacy <3 months must be considered a failure. At the end of round 2, a relative consensus was reached regarding the clinical criterion defining failure (median score = 7/10) and the urodynamic criterion of failure (median score = 8/10). An additional proposal was selected during this second round on the need for a voiding diary (median score = 8/10). CONCLUSION: The first consensus definition of failure of an intradetrusor injection of TB-A for NDO has been achieved with this study: persistence of detrusor overactivity with maximum detrusor pressures >40 cm H2O and/or a compliance issue and/or persistence of urinary incontinence and/or urgency and/or a number of daily self-catheterizations >8/day and/or efficacy <3 months. This study will help to standardize research on the failure of the intradetrusor botulinum toxin for NDO in clinical practice and clinical research.

Microanatomical study of pyramidal neurons in the contralesional somatosensory cortex after experimental ischemic stroke.

At present, many studies support the notion that after stroke, remote regions connected to the infarcted area are also affected and may contribute to functional outcome. In the present study, we have analyzed possible microanatomical alterations in pyramidal neurons from the contralesional hemisphere after induced stroke. We performed intracellular injections of Lucifer yellow in pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere in an ischemic stroke mouse model. A detailed 3-dimensional analysis of the neuronal complexity and morphological alterations of dendritic spines was then performed. Our results demonstrate that pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere show selective changes in their dendritic arbors, namely, less dendritic complexity of the apical dendritic arbor-but no changes in the basal dendritic arbor. In addition, we found differences in spine morphology in both apical and basal dendrites comparing the contralesional hemisphere with the lesional hemisphere. Our results show that pyramidal neurons of remote areas connected to the infarct zone exhibit a series of selective changes in neuronal complexity and morphological distribution of dendritic spines, supporting the hypothesis that remote regions connected to the peri-infarcted area are also affected after stroke.

The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels.

OBJECTIVE: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route. METHODS: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available. RESULTS: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle. CONCLUSIONS: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.

Lidocaine spray vs mepivacaine local infiltration for suturing 1st/2nd grade perineal lacerations: a randomised controlled non-inferiority trial.

BACKGROUND: Perineal lacerations are a very common complication of post-partum. Usually, the repair of 1st and 2nd-grade lacerations is performed after the administration of local anesthesia. Despite the great relevance of the problem, there are only a few studies about the best choice of local anesthetic to use during suturing. We performed a randomised controlled trial to evaluate the efficacy and safety of the use of a local anesthetic spray during the suturing of perineal lacerations in the post-partum. METHODS: We compared the spray with the standard technique, which involves the infiltration of lacerated tissues, using the NRS scale. 136 eligible women who had given birth at University Hospital of Udine were enrolled and randomly assigned to receive nebulization of Lidocaine hydrochloride 10% spray (experimental group) or subcutaneous/submucosal infiltration of mepivacaine hydrochloride (control group) during suturing of perineal laceration. RESULTS: The lacerations included 84 1st-grade perineal traumas (61.7%) and 52 2nd-grade perineal traumas (38.2%). All the procedures were successfully completed without severe complications or serious adverse reactions. There were no statistically significant differences between the two groups in terms of blood losses or total procedure time. Moreover, there were no statistically significant differences in terms of NRS to none of the intervals considered. Regarding the application of the spray in the B group, in 36 cases (52.9%) it was necessary to improve the number of puffs previously supposed to be sufficient (5 puffs). Just in 3 cases, an additional injection was necessary (4.4%). CONCLUSIONS: Our study demonstrates that lidocaine spray alone can be used as a first line of local anesthetic during the closure of I-II-grade perineal lacerations, as it has comparable efficacy to mepivacaine infiltration. TRIAL REGISTRATION: The trial was recorded on https://clinicaltrials.gov . Identification number: NCT05201313. First registration date: 21/01/2022. Unique Protocol ID: 0042698/P/GEN/ARCS.

A novel method for evaluating pseudoallergy based on ß-hexosaminidase and its application for traditional Chinese medicine injections.

Pseudoallergy is a typical and common adverse drug reaction to injections, especially in traditional Chinese medicine injections (TCMIs). At present, the evaluation methods for pseudoallergy include cell methods in vitro and animal methods in vivo. The mast cell evaluation method based on the ß-hexosaminidase (ß-Hex)-catalyzed substrate, 4-nitrophenyl-ß-N-acetyl-D-glucosaminide (4-NPG), is an important method for the evaluation of drug-induced pseudoallergy, but it is prone to false positive results and has insufficient sensitivity. In this study, a novel ß-Hex evaluation system with rat basophilic leukemia-2H3 cells based on high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was established, which effectively increased the sensitivity and avoided false positive results. Cell viabilities were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. In addition, a method for the determination of histamine, which is another indicator in the development of pseudoallergy, was established to validate the above method. The results of this novel method indicated that two TCMIs (Shuxuening injection and Shenqi Fuzheng injection), which were considered to be pseudoallergenic using 4-NPG, were not pseudoallergenic. Overall, the novel ß-Hex/HPLC-FLD evaluation system using Rat basophilic leukemia-2H3 cells established was effective and precise. It could be used for the evaluation of pseudoallergic reactions caused by TCMIs and other injections.

AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests.

PURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies. METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes. RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl ß-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence. CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

Corticosteroid Injection Methods for Frozen Shoulder: A Network Meta-analysis.

OBJECTIVE: To investigate the efficacy of corticosteroid (CS) injection methods for frozen shoulder. DATA SOURCES: PubMed, Embase, and Cochrane Library were searched up to May 6, 2023. STUDY SELECTION: Randomized controlled trials (RCTs) that investigated CS injection methods for frozen shoulder were included. DATA EXTRACTION: Data were extracted independently by 2 authors. Risk of bias was assessed using the RoB 2 tool. DATA SYNTHESIS: A random-effects network meta-analysis was performed within a frequentist framework. The certainty of evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations approach. A total of 66 RCTs involving 4491 patients were included. For short-term outcomes, 4-site injection (vs placebo [PLA]: standardized mean difference [SMD]=-2.20, 95% confidence interval [CI], -2.81 to -1.59 in pain; SMD=2.02; 95% CI, 1.39-2.65 in global function) was the most effective (low certainty). Rotator interval injection was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.07, 95% CI, -1.51 to -0.64 in pain; SMD=0.94, 95% CI, 0.49-1.40 in global function). For midterm outcomes, 4-site injection was most effective (vs PLA: SMD=-1.71, 95% CI, -2.41 to -1.01 in pain; SMD=2.22, 95% CI, 1.34-3.09 in global function; low certainty). Distension via rotator interval (D-RI) was the optimal treatment with moderate to high certainty (vs PLA: SMD=-1.10, 95% CI, -1.69 to -0.51 in pain; SMD=1.46, 95% CI, 0.73-2.20 in global function). Distension and intra-articular injection via anterior or posterior approaches produced effects equivalent to those of rotator interval injection and D-RI. CONCLUSIONS: Rotator interval injection, distension, and intra-articular injection had equivalent effects on symptom relief. More RCTs are required to validate the superiority of multisite injections.

Evaluation of Fluoroscopically Guided Transforaminal Selective Nerve Root Sleeve Injections for Lumbar Spinal Stenosis With Radiculopathy Utilizing Patient Reported Outcome Measurement Information System as an Outcome Measure.

OBJECTIVE: To evaluate the therapeutic effect of transforaminal selective nerve root sleeve injections (TFSNRIs) in a specific subset of patients with clinical symptoms and presentation consistent with spinal stenosis. DESIGN: Retrospective review. SETTING: Tertiary academic spine center. PARTICIPANTS: A total of 176 patients with radicular leg pain with or without low back pain as well as ≥3 clinical features of spinal stenosis and corroborative radiographic features of spinal stenosis on lumbar spine magnetic resonance imaging without confounding spinal pathology (N=176). INTERVENTIONS: Fluoroscopically guided transforaminal selective nerve root sleeve injections. MAIN OUTCOME MEASURES: Patient Reported Outcome Measurement Information System (PROMIS) Physical Function (PF) v1.2/v2.0, Pain Interference (PI) v1.1, and PROMIS (D) v1.0 were collected at baseline and post-procedure short term (<3-months) and long-term (6-12 month) follow-up. Statistical analysis comparing baseline and postprocedural PROMIS scores was performed. Differences were compared with previously established minimal clinically important differences in the spine population. RESULTS: For patients with spinal stenosis treated with TFSNRI, no statistically significant improvement was observed short- and long-term follow-up in PROMIS PF (P=.97, .77) and PROMIS Depression (P=.86, .85) scores. At short-term follow-up, PROMIS PI scores did significantly improve (P=.01) but the average difference of pre- and post-procedure scores did not reach clinical significance. No significant difference in PROMIS PI was noted at long-term follow-up (.75). CONCLUSIONS: Although a statistically significant difference was observed for improvement in pain, in this retrospective study, TFSNRI did not provide clinically significant improvement in patients' function, pain, or depression for lumbar spinal stenosis at short- and long-term follow-up.

Comparison of Particulate Steroid Injection vs Nonparticulate Steroid Injection for Lumbar Radicular Pain: A Systematic Review and Meta-analysis.

OBJECTIVE: The objective of this study was to identify the difference on pain intensity and disability between particulate and nonparticulate steroid injections in patients with lumbar radicular pain. Subgroup analysis by study design, type of particulate steroid, and follow-up duration were performed. DATA SOURCES: We performed the literature search in the PubMed, Embase, and Cochrane Library up March, 2023. STUDY SELECTION: Studies, including randomized controlled trials (RCTs) and nonrandomized studies, that compared particulate steroid injection and nonparticulate steroid injection in patients with lumbar radicular pain were independently reviewed by 2 reviewers for eligibility for inclusion. DATA EXTRACTION: Outcomes of interest were pain intensity and disability. Two reviewers independently assessed the quality of included studies using the revised Cochrane Risk of Bias (RoB2.0) tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions Tool (ROBINS-I) for nonrandomized studies. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD). DATA SYNTHESIS: A total of 10 studies were included in this meta-analysis. The results showed no significant difference in visual analog scale, disability score and the numbers of patients with 50% pain reduction between particulate and nonparticulate steroid injection groups (P>.05). Particulate steroid injections showed significant better effect in pain scale in RCTs (MD=0.62; 95% CI 0.08-1.16, P=.02). In subgroup analysis with steroid types, methylprednisolone showed better effect compared with dexamethasone, while dexamethasone showed better effect compared with betamethasone. CONCLUSIONS: This meta-analysis suggested no significant differences between the particulate and nonparticulate steroid groups in pain or disability score. Therefore, considering the safety profile of nonparticulate steroids, nonparticulate steroid injection may be helpful in patients with lumbar radicular pain.

Effect of intravitreal injections due to neovascular age-related macular degeneration on retinal nerve fiber layer thickness and minimum rim width: a cross sectional study.

PURPOSE: The present study tested the hypothesis that repeated anti-VEGF injections are associated with reduced retinal nerve fiber layer (RNFL) and minimum rim width (MRW) of the optic nerve head. PATIENTS AND METHODS: Sixty-six patients with a history of intravitreal injections due to neovascular age-related macular degeneration were included. RNFL and MRW were measured using optical coherence tomography (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). RESULTS: Mean global RNFL was 90.62 µm and both RNFL as well as MRW significantly decreased with advanced age (p = 0.005 and p = 0.019, respectively). Correlating for the number of injections, no significant impact on RNFL was found globally (p = 0.642) or in any of the sectors. In contrast, however, global MRW was significantly reduced with increasing numbers of intravitreal injections (p = 0.012). The same holds true when adjusted for the confounding factor age (RNFL p = 0.566 and MRW p = 0.023). CONCLUSION: Our study shows that repeated intravitreal injections due to choroidal neovascularization seem to have a deleterious effect on MRW but not on RNFL. This suggests that MRW is a more sensitive marker than RNFL for evaluating the effect of frequent intravitreal injections on the optic nerve head since it seems to be the first structure affected.

Preserving visual acuity: a compelling 12-year case study of controlling neovascular age-related macular degeneration.

INTRODUCTION: In neovascular age-related macular degeneration (nAMD) trials, anti-VEGF injection frequency decreases after the first year, while outcomes remain primarily related to the number of injections. To the best of our knowledge, there are no reports of maintaining the best corrected visual acuity (BCVA) for more than 7 years in extension studies. OBJECTIVE: To report a 12-year follow-up of a real-world case of nAMD where BCVA was preserved from declining. CASE DESCRIPTION: A 67-year-old Caucasian female presented to our department in June 2010 due to decreased vision in her left eye (LE) within the preceding months. Examination showed a BCVA of 85 letters (L) in the right eye (RE) and 35 L in the LE. Fundus examination showed drusen in the macula of both eyes. Macular edema, loss of the macular lutein pigment, macular hypo/hyperpigmentation were observed in the LE. A diagnosis of Type 2 choroidal neovascular membrane (CNV) in the LE was established and within two months a Type 1 CNV developed in the RE. She undergone 9 injections of bevacizumab (six) and ranibizumab (three) within the first year of treatment in the LE and seven injections of ranibizumab within the first year in the RE. RESULTS: The LE had a mean of 5.2 injections per year, and the RE had a mean of 7.5 injections per year, from 2010 to 2022. RE's BCVA dropped by 8L (85L to 77L) and central retinal thickness (CRT) increased by 16 µm (276 µm to 292 µm) while LE's BCVA increased by 28L (35L to 63L) and CRT decreased by 369 µm (680 µm to 311 µm), at the twelfth year. CONCLUSIONS: Although the final visual outcome depends on baseline BCVA and lesion type or size, the number of injections is paramount in preserving BCVA and achieving favorable functional outcomes in nAMD, even after 12 years of treatment.