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Therapeutic Advances in Urology 2024Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of... (Review)
Review
Antibody-drug conjugates and bicycle toxin conjugates represent a tremendous advance in drug delivery technology and have shown great promise in the treatment of urothelial cancer. Previously approved systemic therapies, including chemotherapy and immunotherapy, are often impractical due to comorbidities, and outcomes for patients with advanced disease remain poor, even when receiving systemic therapy. In this setting, antibody-drug and bicycle toxin conjugates have emerged as novel treatments, dramatically altering the therapeutic landscape. These drugs harness unique designs consisting of antibody or bicycle peptide, linker, and cytotoxic payload with more targeted delivery than conventional chemotherapy, thus eliminating malignant cells while reducing systemic toxicities. Potential targets investigated in urothelial cancer include Nectin-4, TROP2, HER2, and EphA2. Initial clinical trials demonstrated efficacy in treatment of refractory advanced urothelial cancer, as well as improvement in quality of life. These initial studies led to FDA approval of two antibody-drug conjugates, enfortumab vedotin and sacituzumab govitecan. Moreover, antibody-drug and bicycle toxin conjugates are being studied in ongoing clinical trials in frontline treatment of advanced disease as well as for localized cancer. These studies highlight the potential for additional future therapies with novel targets, novel antibodies, cytotoxic and immunomodulatory payloads, and unique structural designs enhancing efficacy and safety. There is increasing evidence that combinations with other cancer therapies, especially immunotherapy, improve treatment outcomes. The combination of enfortumab vedotin and pembrolizumab was recently approved for first-line treatment of advanced urothelial carcinoma. Despite the great promise of these novel drugs, robust predictive biomarkers are needed to determine the patients who would maximally benefit. This review surveys the rationale and current state of the evidence for these new drugs and describes future directions actively being explored.
PubMed: 38779496
DOI: 10.1177/17562872241249073 -
Gastroenterology May 2024Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use...
BACKGROUND & AIMS
Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). United States management guidelines suggest their use in patients with persistent abdominal pain, but their specific effect on this symptom has not been assessed systematically.
METHODS
We searched the literature through December 16, 2023, for randomized controlled trials (RCTs) assessing efficacy of BGBTs for adults with IBS, compared with each other or a control intervention. Trials provided an assessment of abdominal pain resolution or improvement at treatment completion. We extracted data as intention-to-treat analyses, assuming dropouts to be treatment failures and reporting pooled relative risks (RRs) of abdominal pain not improving with 95% confidence intervals (CIs), ranking therapies according to the P score.
RESULTS
We identified 42 eligible randomized controlled trials comprising 5220 participants. After treatment completion, the BGBTs with the largest numbers of trials and patients recruited demonstrating efficacy for abdominal pain, specifically, included self-guided/minimal contact cognitive behavioral therapy (CBT) (RR, 0.71; 95% CI, 0.54-0.95; P score, 0.58), face-to-face multicomponent behavioral therapy (RR, 0.72; 95% CI, 0.54-0.97; P score, 0.56), and face-to-face gut-directed hypnotherapy (RR, 0.77; 95% CI, 0.61-0.96; P score, 0.49). Among trials recruiting only patients with refractory global IBS symptoms, group CBT was more efficacious than routine care for abdominal pain, but no other significant differences were detected. No trials were low risk of bias across all domains, and there was evidence of funnel plot asymmetry.
CONCLUSIONS
Several BGBTs, including self-guided/minimal contact CBT, face-to-face multicomponent behavioral therapy, and face-to-face gut-directed hypnotherapy may be efficacious for abdominal pain in IBS, although none was superior to another.
PubMed: 38777133
DOI: 10.1053/j.gastro.2024.05.010 -
Orthopaedic Surgery May 2024Frozen shoulder (FS) is a painful and debilitating condition affecting the shoulder joint. When patients fail to improve after conservative treatments, operative... (Review)
Review
OBJECTIVE
Frozen shoulder (FS) is a painful and debilitating condition affecting the shoulder joint. When patients fail to improve after conservative treatments, operative treatments including arthroscopic capsular release (ACR) and manipulation under anesthesia (MUA) are recommended. However, the comparison between these two interventions remains controversial. This study aimed to compare the efficacy and safety of ACR and MUA for refractory FS.
METHODS
A systematic review and meta-analysis was conducted following the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. PubMed, EMBASE, Cochrane Library, and Web of Science were searched for eligible studies until December 10, 2023. Meta-analyses were conducted using Manager V.5.3.3. Pooled effect sizes were expressed as the weighted mean difference (WMD) or odds ratio (OR) with 95% confidence intervals (CIs).
RESULTS
A total of eight comparative studies with 768 patients were included. Compared with MUA, ACR had statistically better Δ VAS (WMD, -0.44; 95% CI, -0.71 to -0.18; I = 6%; p = 0.001) at over 12-month follow-up, which did not reach the minimal clinically important difference (MCID). Other outcomes regarding pain relief, function, and range of motion (ROM) improvements were not statistically different between the two groups at different follow-up timepoints. Compared with the MUA group, the ACR group had a significantly higher rate of severe complications (OR, 4.14; 95% CI, 1.01 to 16.94; I2 = 0%; p = 0.05), but comparable rates of mild complications and additional intervention.
CONCLUSIONS
In treating refractory FS, ACR demonstrated comparable pain relief, functional and ROM improvements, rates of mild complications and additional intervention but a higher risk of severe complications to MUA during short-term follow-up periods. Notably, ACR exhibited statistically superior improvement in the long-term pain relief compared to the MUA group, although it did not reach the MCID.
PubMed: 38747000
DOI: 10.1111/os.14077 -
Journal of Neurosciences in Rural... 2024Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading... (Review)
Review
OBJECTIVES
Epilepsy poses a significant challenge in pediatric and adolescent populations, impacting not only seizures but also psychological and cognitive comorbidities, leading to higher mortality rates than the general population. Drug-refractory epilepsy, resistant to conventional treatments, affects a range of 7-20% of pediatric patients. The search for alternative therapies has led to exploring the therapeutic potential of L. compounds, particularly cannabidiol (CBD). Examine the use of CBD for treating drug-refractory epilepsy in children and young adults, summarizing existing evidence on its efficacy.
MATERIALS AND METHODS
A systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, assessed studies from 2018 to 2023, focusing on CBD's efficacy and safety for treatment-resistant epilepsy in pediatric and juvenile populations. The search spanned seven databases, and the studies underwent rigorous screening and data extraction.
RESULTS
Out of 6351 identified articles, eight were selected for review. The included studies reported positive outcomes, with CBD leading to a reduction in seizure frequency ranging from 50% to complete seizure freedom. Adverse effects were mostly mild and reversible, including drowsiness, diarrhea, and loss of appetite.
CONCLUSION
The CBD emerges as a promising tool for refractory epilepsy in pediatric patients, showing efficacy in reducing seizure frequency and improving overall quality of life. Despite mild and reversible adverse effects, CBD's benefits outweigh the risks. However, more research on long-term effects is needed to fully understand its implications.
PubMed: 38746511
DOI: 10.25259/JNRP_618_2023 -
Annals of Medicine Dec 2024Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an... (Meta-Analysis)
Meta-Analysis
Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis.
BACKGROUND
Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL.
METHODS
The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
RESULTS
Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles.
CONCLUSION
Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.
Topics: Humans; Immunotherapy, Adoptive; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antigens, CD19; Sialic Acid Binding Ig-like Lectin 2; Receptors, Chimeric Antigen; Child; Treatment Outcome; Neoplasm, Residual; Cytokine Release Syndrome; Recurrence; Neurotoxicity Syndromes
PubMed: 38738799
DOI: 10.1080/07853890.2024.2349796 -
CVIR Endovascular May 2024Internal hemorrhoids (IH) is a common medical condition that can result in morbidity secondary to bleeding and discomfort. Treatment for IH has traditionally consisted... (Review)
Review
Common design and data elements on rectal artery embolization for treatment of symptomatic internal hemorrhoidal disease: an interactive systematic review of clinical trials.
BACKGROUND
Internal hemorrhoids (IH) is a common medical condition that can result in morbidity secondary to bleeding and discomfort. Treatment for IH has traditionally consisted of dietary and conservative medical management, focal treatments including banding and sclerotherapy or hemorrhoidectomy. Recently, rectal artery embolization (RAE) has been studied as a potential treatment for bleeding predominant IH. We performed a common design and data element analysis of studies that report on RAE.
MATERIALS AND METHODS
We conducted a qualitative systematic literature review for rectal artery embolization (RAE) for symptomatic hemorrhoidal disease. The screening process involved five online databases (PubMed, Embase, Google Scholar, DOAJ, and Scopus). Additionally, ClinicalTrials.gov was examined for active, unpublished completed studies. The initial search yielded 2000 studies, with 15 studies meeting the inclusion criteria after screening and assessment. The included studies comprised one RCT, one case series, one pilot study and 12 cohort studies.
RESULTS
The population analysis revealed a male predominance across all studies, with varying cohort sizes. The baseline Goligher hemorrhoid grade was utilized in 80% of studies. The majority (73.3%) employed a transfemoral approach, and coils were the primary embolic material in 60% of studies, 26.6% were combination of coils and particles, and 6.6% were particles only. Patient selection criteria highlighted RAE's applicability for high surgical risk patients and those with anemia, chronic hematochezia, or treatment-refractory cases. Exclusion criteria emphasized factors such as previous surgeries, colorectal cancer, rectal prolapse, acute hemorrhoidal complications, and contrast allergy. Study designs varied, with cohort studies being the most common (12/15; 80%). Procedural details included the use of metallic coils and detachable micro-coils, with a high technical success rate reported in most studies ranging from 72 to 100%. The follow-up ranged from 1 to 18 months. The majority of studies reported no major immediate or post-procedural complications.
CONCLUSION
While all studies focused on RAE as a treatment for IH, there was a great degree of heterogeneity among included studies, particularly regarding inclusion criteria, exclusion criteria, outcomes measures and timeframe. Future literature should attempt to standardize these design elements to help facilitate secondary analyses and increase understanding of RAE as a treatment option.
PubMed: 38733497
DOI: 10.1186/s42155-024-00458-2 -
International Journal of Molecular... May 2024Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell)... (Meta-Analysis)
Meta-Analysis Review
An Assessment of the Effectiveness and Safety of Chimeric Antigen Receptor T-Cell Therapy in Multiple Myeloma Patients with Relapsed or Refractory Disease: A Systematic Review and Meta-Analysis.
Multiple myeloma (MM), the second most common hematologic malignancy, remains incurable, and its incidence is rising. Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a novel treatment, with the potential to improve the survival and quality of life of patients with relapsed/refractory multiple myeloma (rrMM). In this systematic review and meta-analysis, conducted in accordance with PRISMA guidelines, we aim to provide a concise overview of the latest developments in CAR-T therapy, assess their potential implications for clinical practice, and evaluate their efficacy and safety outcomes based on the most up-to-date evidence. A literature search conducted from 1 January 2019 to 12 July 2023 on Medline/PubMed, Scopus, and Web of Science identified 2273 articles, of which 29 fulfilled the specified criteria for inclusion. Our results offer robust evidence supporting CAR-T cell therapy's efficacy in rrMM patients, with an encouraging 83.21% overall response rate (ORR). A generally safe profile was observed, with grade ≥ 3 cytokine release syndrome (CRS) at 7.12% and grade ≥ 3 neurotoxicity at 1.37%. A subgroup analysis revealed a significantly increased ORR in patients with fewer antimyeloma regimens, while grade ≥ 3 CRS was more common in those with a higher proportion of high-risk cytogenetics and prior exposure to BCMA therapy.
Topics: Multiple Myeloma; Humans; Immunotherapy, Adoptive; Receptors, Chimeric Antigen; Treatment Outcome; Quality of Life; Neoplasm Recurrence, Local; Cytokine Release Syndrome
PubMed: 38732213
DOI: 10.3390/ijms25094996 -
Translational Andrology and Urology Apr 2024Priapism is a rare condition characterized by persistent erection of the penis that lasts more than 4 hours in the absence of sexual stimulation and is associated with... (Review)
Review
BACKGROUND
Priapism is a rare condition characterized by persistent erection of the penis that lasts more than 4 hours in the absence of sexual stimulation and is associated with significant morbidity and complications, including erectile dysfunction and penile fibrosis. Surgical management of priapism can be extremely challenging. We herein provide a comprehensive review that aims to evaluate the role of penile prosthesis (PP) implantation in the management of priapism.
METHODS
A systematic literature search was performed using the following databases: PubMed, Embase, and Scopus to identify studies that evaluated the effectiveness of PP implantation in treating priapism and the long-term complications, outcomes, and patients' satisfaction rate.
RESULTS
Out of 717 English-language studies published between 2002 and 2022, 17 were chosen for this review. Majority of patients had a malleable PP (MPP) implant, either early or delayed after the priapism episode. Early placement (EP) of PP is widely defined between studies ranging from less than 72 hours, within 1 week, and within 3 weeks. Most common causes of priapism were sickle cell anemia (SCA), medication-induced, and idiopathic. Studies show a higher satisfaction rate ranging between 80% and 100%, with sexual intercourse achievement ranging between 64.2% and 100%. Based on the GRADE system, included studies rated as very low quality of evidence. Commonly reported complications that arise after PP procedures, include device infection, erosion, curvature, and mechanical malfunction, such as auto-inflation.
CONCLUSIONS
PP can be an effective treatment option for priapism, particularly in cases of ischemic priapism lasting more than 36 hours or recurrent priapism that is medically refractory. However, due to the very low quality of evidence, larger, well-designed studies are warranted where long-term outcomes, patients' satisfaction, and complications following priapism-related PP implantation are measured as endpoints.
PubMed: 38721288
DOI: 10.21037/tau-23-224 -
Cureus Apr 2024A significant contributor to blindness and visual impairment globally is uncorrected refractive error. To plan effective interventions, eye care professionals must... (Review)
Review
A significant contributor to blindness and visual impairment globally is uncorrected refractive error. To plan effective interventions, eye care professionals must promptly identify people at a high risk of acquiring myopia, and monitor disease progress. Artificial intelligence (AI) and machine learning (ML) have enormous potential to improve diagnosis and treatment. This systematic review explores the current state of ML and AI applications in the diagnoses and treatment of refractory errors in optometry. A systematic review and meta-analysis of studies evaluating the diagnostic performance of AI-based tools in PubMed was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. To find relevant studies on the use of ML or AI in the diagnosis or treatment of refractive errors in optometry, a thorough search was conducted in various electronic databases such as PubMed, Google Scholar, and Web of Science. The search was limited to studies published between January 2015 and December 2022. The search terms used were "refractive errors," "myopia," "optometry," "machine learning," "ophthalmology," and "artificial intelligence." A total of nine studies met the inclusion criteria and were included in the final analysis. ML is increasingly being utilized for automating clinical data processing as AI technology progresses, making the formerly labor-intensive work possible. AI models that primarily use a neural network demonstrated exceptional efficiency and performance in the analysis of vast medical data, rivaling board-certified, healthcare professionals. Several studies showed that ML models could support diagnosis and clinical decision-making. Moreover, an ML algorithm predicted future refraction values in patients with myopia. AI and ML models have great potential to improve the diagnosis and treatment of refractive errors in optometry.
PubMed: 38711688
DOI: 10.7759/cureus.57706 -
Skin Research and Technology : Official... May 2024Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation....
BACKGROUND
Notalgia paresthetica (NP) is a rare condition characterized by localized pain and pruritus of the upper back, associated with a distinct area of hyperpigmentation. Given the lack of standardized treatment and the uncertain efficacy of available options, applying procedural methods is of growing interest in treating NP.
AIMS
We sought to comprehensively evaluate the role of procedural treatments for NP.
METHODS
We systematically searched PubMed/Medline, Ovid Embase, and Web of Science until November 14th, 2023. We also performed a citation search to detect all relevant studies. Original clinical studies published in the English language were included.
RESULTS
Out of 243 articles, sixteen studies have reported various procedural modalities, with or without pharmacological components, in treating NP. Pharmacological procedures, including injections of botulinum toxin, lidocaine, and corticosteroids, led to a level of improvement in case reports and case series. However, botulinum toxin did not show acceptable results in a clinical trial. Moreover, non-pharmacological procedures were as follows: physical therapy, exercise therapy, kinesiotherapy, acupuncture and dry needling, electrical muscle stimulation, surgical decompression, and phototherapy. These treatments result in significant symptom control in refractory cases. Physical therapy can be considered a first-line choice or an alternative in refractory cases.
CONCLUSION
Procedural modalities are critical in the multidisciplinary approach to NP, especially for patients who are refractory to topical and oral treatments. Procedural modalities include a spectrum of options that can be applied based on the disease's symptoms and severity.
Topics: Humans; Pruritus; Lidocaine; Paresthesia; Hyperpigmentation; Physical Therapy Modalities; Acupuncture Therapy; Botulinum Toxins; Anesthetics, Local; Exercise Therapy; Adrenal Cortex Hormones; Dry Needling
PubMed: 38696233
DOI: 10.1111/srt.13723