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Surgical Endoscopy Jun 2024Pudendal nerve entrapment (PNE) is an underdiagnosed condition affecting a spectrum of pelvic functions, primarily pain, as outlined by Nantes diagnostic criteria.... (Review)
Review
BACKGROUND
Pudendal nerve entrapment (PNE) is an underdiagnosed condition affecting a spectrum of pelvic functions, primarily pain, as outlined by Nantes diagnostic criteria. Although numerous surgical decompression techniques are available for its management, consensus on efficacy and safety is lacking. This study conducts a systematic review and meta-analysis to assess the efficacy and complication rates of the main surgical decompression techniques.
METHODS
A comprehensive literature search was conducted in PubMed®, Embase®, Web of Science®, and ClinicalTrails.gov® on 19th of April 2023. Initial screening involved title and abstract evaluation, with subsequent retrieval and assessment of abstracts and full-text articles. Studies assessing pain outcomes before and after surgical release of the pudendal nerve were included. Studies without full-text, focusing on diagnostic methods or with outcomes relating solely to LUTS, digestive symptoms, or sexual dysfunction, were excluded. Risk of bias assessement was conducted using the National Institute of Health (NIH) Study Quality Assessment tool. Studies were categorized based on three surgical techniques: perineal, transgluteal, and laparoscopic transperitoneal. Random-effects meta-analysis with subgroup analysis were used. Meta-regression analyses were conducted to investigate the influence of covariates on the observed outcomes.
RESULTS
Nineteen studies, comprising 810 patients, were included. The overall significant pain relief rate across all techniques was estimated at 0.67 (95% CI 0.54 to 0.78) with considerable heterogeneity (I = 80.4%). Subgroup analysis revealed success rate for different techniques: laparoscopic (0.91, 95% CI 0.64 to 0.98), perineal (0.69, 95% CI 0.52 to 0.82), and transgluteal (0.50, 95% CI 0.37 to 0.63). The laparoscopic technique exhibited a complication rate of 16.0%. Meta-regression indicated that patient age and median follow-up significantly influenced outcomes.
CONCLUSION
While comparing surgical techniques is challenging, this meta-analysis highlights important outcome differences. The laparoscopic technique appears most promising for pain improvement. However, the study also emphasizes the need for further robust, long-term research due to significant heterogeneity across studies and prevelent risk of bias. PROSPERO database: CRD42023496564.
PubMed: 38942945
DOI: 10.1007/s00464-024-10990-w -
Surgical and Radiologic Anatomy : SRA Jun 2024Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative... (Review)
Review
INTRODUCTION
Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction.
MATERIALS AND METHODS
A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions.
RESULTS
The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies.
CONCLUSION
US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively.
PubMed: 38942935
DOI: 10.1007/s00276-024-03429-3 -
Scientific Reports Jun 2024Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic...
Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.
Topics: Humans; Crohn Disease; Ustekinumab; Male; Female; Adult; Treatment Outcome; Middle Aged; Prospective Studies; Follow-Up Studies; Remission Induction; Hungary
PubMed: 38942890
DOI: 10.1038/s41598-024-65987-1 -
PAM-flexible Engineered FnCas9 variants for robust and ultra-precise genome editing and diagnostics.Nature Communications Jun 2024The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a...
The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a negligible affinity for mismatched substrates, but its low cellular targeting efficiency limits therapeutic use. Here, we rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants and broaden their accessibility across human genomic sites by ~3.5-fold. The enFnCas9 proteins with single mismatch specificity expanded the target range of FnCas9-based CRISPR diagnostics to detect the pathogenic DNA signatures. They outperform Streptococcus pyogenes Cas9 (SpCas9) and its engineered derivatives in on-target editing efficiency, knock-in rates, and off-target specificity. enFnCas9 can be combined with extended gRNAs for robust base editing at sites which are inaccessible to PAM-constrained canonical base editors. Finally, we demonstrate an RPE65 mutation correction in a Leber congenital amaurosis 2 (LCA2) patient-specific iPSC line using enFnCas9 adenine base editor, highlighting its therapeutic utility.
Topics: Humans; Gene Editing; CRISPR-Associated Protein 9; CRISPR-Cas Systems; Francisella; Bacterial Proteins; Leber Congenital Amaurosis; Streptococcus pyogenes; HEK293 Cells; Mutation; RNA, Guide, CRISPR-Cas Systems; Protein Engineering; Genome, Human
PubMed: 38942756
DOI: 10.1038/s41467-024-49233-w -
Scientific Reports Jun 2024Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in...
Self-reported shorter/longer sleep duration, insomnia, and evening preference are associated with hyperglycaemia in observational analyses, with similar observations in small studies using accelerometer-derived sleep traits. Mendelian randomization (MR) studies support an effect of self-reported insomnia, but not others, on glycated haemoglobin (HbA1c). To explore potential effects, we used MR methods to assess effects of accelerometer-derived sleep traits (duration, mid-point least active 5-h, mid-point most active 10-h, sleep fragmentation, and efficiency) on HbA1c/glucose in European adults from the UK Biobank (UKB) (n = 73,797) and the MAGIC consortium (n = 146,806). Cross-trait linkage disequilibrium score regression was applied to determine genetic correlations across accelerometer-derived, self-reported sleep traits, and HbA1c/glucose. We found no causal effect of any accelerometer-derived sleep trait on HbA1c or glucose. Similar MR results for self-reported sleep traits in the UKB sub-sample with accelerometer-derived measures suggested our results were not explained by selection bias. Phenotypic and genetic correlation analyses suggested complex relationships between self-reported and accelerometer-derived traits indicating that they may reflect different types of exposure. These findings suggested accelerometer-derived sleep traits do not affect HbA1c. Accelerometer-derived measures of sleep duration and quality might not simply be 'objective' measures of self-reported sleep duration and insomnia, but rather captured different sleep characteristics.
Topics: Humans; Mendelian Randomization Analysis; Glycated Hemoglobin; Accelerometry; Sleep; Blood Glucose; Male; Female; Middle Aged; Adult; Self Report; Aged; Sleep Initiation and Maintenance Disorders
PubMed: 38942746
DOI: 10.1038/s41598-024-58007-9 -
Clinical Therapeutics Jun 2024Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy...
PURPOSE
Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA.
METHODS
This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity.
FINDINGS
There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events.
IMPLICATIONS
Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.
PubMed: 38942719
DOI: 10.1016/j.clinthera.2024.05.007 -
Clinical Radiology Jun 2024This study assesses the safety and efficacy of particle embolization during bronchial artery embolization (BAE) in patients with shunts between bronchial and...
AIM
This study assesses the safety and efficacy of particle embolization during bronchial artery embolization (BAE) in patients with shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery.
METHODS
In this retrospective, single-center study, we analyzed 312 BAE procedures performed from June 2020 to April 2023. The patient cohort had shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery. We meticulously collected and examined comprehensive data, including clinical characteristics, computed tomography (CT) imaging, and embolization procedural details.
RESULTS
Vascular shunts were identified in 49 patients. The etiologies of hemoptysis included post-TB sequelae (42.8%), bronchiectasis (26.5%), active TB (12.2%), aspergilloma (8.1%), bacterial pneumonia (4.1%), lung cancer (4.1%), and non-tuberculous mycobacterial infection (2%). The technical success rate of the procedures was 98%, with 149 out of 152 identified vessels successfully embolized. All patients experienced cessation or significant reduction of hemoptysis within 24 hours following the procedure. The clinical success rates were 97.9% at one month, 93.9% at six months, and 89.8% at one year. No shunt-related complications were detected.
CONCLUSION
BAE with particle embolization is a safe and effective treatment for hemoptysis, particularly in cases with complex shunts between bronchial and non-bronchial systemic arteries and the pulmonary artery.
PubMed: 38942705
DOI: 10.1016/j.crad.2024.06.003 -
Clinical Colorectal Cancer May 2024Pembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic...
BACKGROUND
Pembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (CRC). We evaluated vicriviroc (small-molecule C-C motif chemokine ligand 5 antagonist) plus pembrolizumab in patients with advanced or metastatic MSS/pMMR CRC.
PATIENTS AND METHODS
This open-label, phase 2 trial (NCT03631407) enrolled adults with histologically confirmed, locally advanced, unresectable or metastatic CRC that was MSS per local assessment. All patients had received previous treatment with standard therapies. Patients were randomized 1:1 to vicriviroc 150 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or vicriviroc 250 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (2 years). Primary endpoints were the objective response rate (ORR) as assessed by the investigator per RECIST v1.1, dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs.
RESULTS
Forty patients were enrolled and treated. ORR was 5% (95% CI, 0.1%-24.9%) in both treatment groups. There were no complete responses; 1 patient in each treatment group experienced a partial response. No patient in the vicriviroc 150 mg plus pembrolizumab group experienced a DLT. Two patients in the vicriviroc 250 mg plus pembrolizumab group experienced DLTs (1 grade 4 encephalopathy and 1 grade 4 pneumonitis).
CONCLUSION
The combination of vicriviroc at doses of 150 or 250 mg plus pembrolizumab 200 mg showed limited antitumor activity in patients with advanced or metastatic MSS/pMMR CRC. Toxicity with the combination was manageable.
PubMed: 38942693
DOI: 10.1016/j.clcc.2024.05.003 -
Academic Radiology Jun 2024The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for...
RATIONALE AND OBJECTIVES
The objective of this study was to measure the safety and efficacy of thermal ablation, including radiofrequency ablation (RFA) and microwave ablation (MWA), for patients with stage I non-small cell lung cancer (NSCLC).
MATERIALS AND METHODS
The databases PubMed was searched from inception to November 2023 to identify relevant studies. Statistical analyses were performed with R version 3. 6. 3.
RESULTS
Thirty-three studies involving 1400 patients were finally included. According to our study, the incidence of patients with stage I NSCLC who were older than 60 years old was 98 % (95 % CI [94-100 %]); the lesions were mostly located in RUL (Right Upper Lobe) and LUL (Left Upper Lobe), and the incidence of the two sites was 29 % (95 % CI [23-35 %]) and 27 % (95 % CI [21-33 %]), respectively; the types of lung cancers mainly included adenocarcinoma, squamous carcinoma, and large-cell lung cancer, of which adenocarcinoma accounted for the largest proportion of 63 % (95 % CI [56-70 %]); the causes of death were mainly categorized into cancer-related (57 %, 95 %CI[40-74 %]) and noncancer-related (40 %, 95 %CI [23-58 %]); the common complications in the postoperative period were pneumothorax and pain, with the incidence of 33 % (95 %CI[24-44 %]) and 33 % (95 %CI[19-50 %]), and the rate of the postoperative complications in MWA was slightly higher than those in RFA; the local recurrence rate was 23 % (95 %CI[17-29 %]) and the distant recurrence rate was 18 % (95 %CI[7-32 %]); the pooling result showed the rate of 1-, 2-, 3-, and 5-year survival rate were 96 %, 81 %, 68 %, and 42 %, the Cancer-specific survival (CSS) rates at 1, 2, 3, and 5 years were 98 %, 88 %, 75 %, and 58 %, Disease-free survival (DFS) rates at 1, 2, 3, and 5 years were 87 %, 63 %, 57 %, and 42 %, there were no significant differences existed between the RFA group and MWA group in survival rate, CSS and DFS.
CONCLUSION
Ablation therapy is safe and effective for stage I NSCLC patient. MWA and RFA have comparable efficacy, safety, and prognosis, which could be recommended for patients with stageⅠNSCLC, especially for patients who cannot tolerate open surgery.
PubMed: 38942645
DOI: 10.1016/j.acra.2024.05.038 -
RMD Open Jun 2024To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and... (Randomized Controlled Trial)
Randomized Controlled Trial
Nipocalimab, an anti-FcRn monoclonal antibody, in participants with moderate to severe active rheumatoid arthritis and inadequate response or intolerance to anti-TNF therapy: results from the phase 2a IRIS-RA study.
OBJECTIVES
To investigate the efficacy, safety, pharmacokinetics and pharmacodynamics of nipocalimab in participants with moderate to severe active rheumatoid arthritis (RA) and inadequate response or intolerance to ≥1 antitumour necrosis factor agent.
METHODS
In this phase 2a study, participants with RA seropositive for anticitrullinated protein antibodies (ACPA) or rheumatoid factors were randomised 3:2 to nipocalimab (15 mg/kg intravenously every 2 weeks) or placebo from Weeks 0 to 10. Efficacy endpoints (primary endpoint: change from baseline in Disease Activity Score 28 using C reactive protein (DAS28-CRP) at Week 12) and patient-reported outcomes (PROs) were assessed through Week 12. Safety, pharmacokinetics and pharmacodynamics were assessed through Week 18.
RESULTS
53 participants were enrolled (nipocalimab/placebo, n=33/20). Although the primary endpoint did not reach statistical significance for nipocalimab versus placebo, a numerically higher change from baseline in DAS28-CRP at Week 12 was observed (least squares mean (95% CI): -1.03 (-1.66 to -0.40) vs -0.58 (-1.24 to 0.07)), with numerically higher improvements in all secondary efficacy outcomes and PROs. Serious adverse events were reported in three participants (burn infection, infusion-related reaction and deep vein thrombosis). Nipocalimab significantly and reversibly reduced serum immunoglobulin G, ACPA and circulating immune complex levels but not serum inflammatory markers, including CRP. ACPA reduction was associated with DAS28-CRP remission and 50% response rate in American College of Rheumatology (ACR) criteria; participants with a higher baseline ACPA had greater clinical improvement.
CONCLUSIONS
Despite not achieving statistical significance in the primary endpoint, nipocalimab showed consistent, numerical efficacy benefits in participants with moderate to severe active RA, with greater benefit observed for participants with a higher baseline ACPA.
TRIAL REGISTRATION NUMBER
NCT04991753.
Topics: Humans; Arthritis, Rheumatoid; Male; Female; Middle Aged; Treatment Outcome; Antirheumatic Agents; Severity of Illness Index; Antibodies, Monoclonal, Humanized; Aged; Adult; Tumor Necrosis Factor-alpha; Double-Blind Method; Patient Reported Outcome Measures; Anti-Citrullinated Protein Antibodies
PubMed: 38942592
DOI: 10.1136/rmdopen-2024-004278