Established Efficacy Research Articles

Unveiling Current Advances in Bioelectronic Medicine: A Comprehensive Review

Background: Bioelectronic medicine is an emerging therapy that makes use of neural signals and the nervous system to help in the treatment of injuries and diseases. The nervous sys-tem consists of disciplined circuits that involve the communication of every major organ of the human body as all the organs of the human body are regulated and controlled by neural circuits. Objective: The objective of this review is to overview the current implementations of bioelectron-ic medicines within the human body. The main target is to heal the body without administering a wide array of exogenous drugs. On understanding these neural circuits at a molecular level, it could be possible to understand, manipulate, and modify the body’s functioning with the help of electrical impulses to modify neural impulses. Methods: The literature related to bioelectronic medicines, and their applications was collected through different websites, academic research portals, and databases, sorted, and presented in this review. Results: Bioelectronic medicine is emerging as a cutting-edge area in healthcare, demonstrating its potential to transform the diagnosis and management of inflammation and related conditions. With established efficacy in a variety of disorders and marketed available treatments, it highlights an enormous shift toward individualized and specialized therapeutic approaches, providing prom-ise for improved outcomes and a higher quality of life for patients worldwide. Conclusion: The study focuses on potential advances in bioelectronic medicine for alleviating in-flammation and inflammatory disorders such as rheumatoid arthritis, diabetes, and spinal cord in-jury. Bioelectronic treatments provide innovative therapeutic options with the potential for con-siderable clinical effects.

Surgical Trends in Chronic Pancreatitis from 2014 Through 2021.

We analyzed annual surgical trends for benign chronic pancreatitis (CP), studying specifically mortality, morbidity, and pancreatic fistula rates. We also aimed to identify predictors of pancreatic fistula formation. For this analysis, we used data from the American College of Surgeons National Surgical Quality Improvement Program from 2014 through 2021. The study included patients who underwent surgery for benign CP. Data collected included patient demographics, preoperative variables, and postoperative outcomes. Data were analyzed with univariate and multivariate analyses, with significance defined as P ≤ .05. Over the study period, the number of pancreatic surgical procedures increased 49.3%, although surgery specifically for CP declined by 31.7%. The rate of pancreatic fistula formation decreased 44.9%, and mortality decreased 31.9%. Significant predictors of a pancreatic fistula included no diabetes, preoperative sepsis, soft texture of the pancreatic gland, and greater patient weight. Surgery for benign CP decreased substantially despite the established efficacy of surgical intervention for long-term pain management. The concurrent decline in mortality and rates of pancreatic fistula formation suggest advances over the study years in surgical and postoperative care.

Enhancing Utilisation of Intraosseous Vascular Access in Cardiac Arrest Management: Insights From a Retrospective Study.

Intraosseous (IO) vascular access is a crucial intervention during cardiac arrest scenarios, providing a reliable route for emergency medication administration and fluid resuscitation in the absence of a stable intravenous (IV) line or central line. Despite its established efficacy, our retrospective study at Southampton General Hospital revealed under-utilisation rates of IO insertions during cardiac arrests. Among 131 patients studied over a year, only a minority received IO lines. Our findings underscore the need for improved awareness, training, and institutional support to optimise the use of IO vascular access in critical care settings. Our study also highlights, within the limitations of this study, the positive effect an IO has when utilised effectively, in the absence of an IV, in relation to Return Of Spontaneous Circulation (ROSC) rates highlighting and supporting the usage of IO lines in the event an IV is unattainable or difficult to insert.

A Mindfulness-Integrated Therapeutic Approach to Enhance Client Engagement with Prolonged Exposure and Habit Reversal Therapy and Bolster Therapist Trainee Self-Efficacy and Distress Tolerance

Despite the established efficacy of exposure-based trauma treatments, such as prolonged exposure (PE), clinicians’ and clients’ concerns about these therapies hinder their widespread implementation. Clinicians report experiencing low self-efficacy and high distress when delivering PE, while patients doubt the credibility of this treatment, contributing to patient dropout. To tackle such challenges, mindfulness-based therapeutic approaches have been used. In the current case involving PTSD due to childhood sexual abuse (CSA) and coercive sex, trichotillomania, excoriation disorder, and depression, mindfulness practices and principles were woven into PE and habit reversal therapy (HRT). The therapist, a trainee with no prior trauma treatment experience, felt that her ability to manage the client’s distress during treatment and her confidence in delivering therapy was enhanced by her own mindfulness practice, and further reinforced by the pervasive integration of mindfulness throughout treatment. Likewise, the client attributed her capacity to engage in PE and HRT to the mindfulness practices and principles woven into treatment. Mindfulness also assisted in coalescing the concomitant delivery of PE and HRT. Following 21 sessions of mindfulness-integrated PE and 17 sessions of mindfulness-integrated HRT, the client no longer met criteria for PTSD and depression, eradicated her body-focused repetitive behaviors (BFRBs), and disclosed her index trauma with loved ones. These improvements were maintained at one-year follow-up, underscoring the potency of mindfulness therapeutic integration to enhance therapists’ distress tolerance and self-efficacy, clients’ treatment engagement, and overall therapeutic outcomes in complex cases.

Safety and Efficacy of Moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: a meta-analysis

Abstract Background Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide, poses an important healthcare challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. Purpose This meta-analysis seeks to assess the impact of moderate-intensity statin plus ezetimibe (MIS+EZT) versus high-intensity statin monotherapy (HIS) on LDL < 70mg/dl; Total Cholesterol; LDL; High Density Cholesterol (HDL) and triglycerides levels. Our goal is to synthesize the existing evidence and pinpoint areas that warrant further investigation. Methods A thorough literature search was conducted across PubMed, Scopus, Web of Science, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. Results In the 13 included studies, involving 8,592 patients, of which 4,525 (52.67%) received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 12 to 219 weeks, with participant ages varying from 66 to 76.5 years in the MIS+EZT group and from 67 to 75.9 years in the HIS group. Analysis revealed significant MIS+EZT-associated with greater percentages in Low Density Lipoprotein (LDL) < 70 (Odds Ratio (OR) 1.76; 95% CI [1.26; 2.45]; p=0.001; I²=73%), LDL reduction (Mean Difference (MD) -5.05 mg/dL; 95% CI [-9.02;-1.07]; p<0.013; I²=56%;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95% CI [-14.90; -0.91]; p<0.027; I²=60%); Triglycerides reduction (MD -8.20 mg/ dL; 95% CI [-13.05; -3.35]; p<0.001; I²=2%;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95% CI [0.79; 1.78]; p=0.404; I²=0%); and Drug intolerance (RR 0.78 ; 95% CI [0.32; 1.92]; p=0.584; I²=35%). Conclusions This meta-analysis underscores the effectiveness of MIS+EZT in enhancing significant clinical outcomes for ASCVD patients, as evidenced by improvements in a greater percentage of patients achieved the LDL <70 target, LDL, Total Cholesterol and Triglycerides levels . Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

No Evidence Support Quetiapine in Treatment of Adolescent Bipolar Depression

Quetiapine, an atypical antipsychotic with established efficacy in the treatment of schizophrenia, shows efficacy in the treatment of acute mania and depression associated with bipolar disorder. Quetiapine, either as monotherapy or in combination with lithium or divalproex sodium, is generally well tolerated and effective in reducing manic symptoms in adult and adolescent patients with acute bipolar mania, and is approved for use in adults for this indication. As monotherapy, the drug is also effective in reducing depressive symptoms in patients with bipolar depression. It is associated with a low incidence of Extrapyramidal Symptom (EPS)-related adverse events and low EPS ratings in bipolar disorder. Quetiapine thus shows potential in the treatment of bipolar depression, and represents a useful agent for the treatment of acute bipolar mania. But for children and adolescent, quetiapine show no difference to placebo. The both RCT and evidence-based medicine study indicate that quetiapine have no efficacy for children and adolescent bipolar depression.

A tailored machine learning approach for mortality prediction in severe COVID-19 treated with glucocorticoids.

<sec><title>BACKGROUND</title>The impact of severe COVID-19 pneumonia on healthcare systems highlighted the need for accurate predictions to improve patient outcomes. Despite the established efficacy of glucocorticoids (GCs), variable patient responses are observed, and the existing clinical scores are limited in predicting non-responders. We propose a machine learning (ML) based approach to predict mortality in COVID-19 pneumonia treated with GCs.</sec><sec><title>METHODS</title>This is an ML-driven retrospective analysis involving 825 patients. We leveraged XGBoost to select the most appropriate features from the initial 52, including clinical and laboratory data. Six different ML techniques were compared. Shapley additive explanation (SHAP) values were used to describe the influence of each feature on classification. Internal validation was performed.</sec><sec><title>RESULTS</title>Nine key predictors of death were identified: increasing C-reactive protein (CRP), decreasing arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂), age, coronary artery disease, invasive mechanical ventilation, acute renal failure, chronic heart failure, PaO₂/FiO₂ earliest value, and body mass index. Random forest achieved the highest test area under the receiver operating characteristic curve at 0.938 (95% CI 0.903-0.969). SHAP values highlighted age and PaO₂/FiO₂ improvement as the most influential features; the latter showed a higher impact than CRP reduction over time.</sec><sec><title>CONCLUSION</title>The proposed ML algorithm effectively predicts the risk of hospital death in COVID-19 pneumonia patients undergoing GCs. This approach can be adapted to datasets measuring similar clinical variables.</sec>.

The surface deformation of permafrost and active layer thickness in the upper reaches of the Black River basin, revealed by InSAR observations and independent component analysis

The Heihe River Basin, located in the northeastern part of the Qinghai-Tibetan Plateau, is part of the perennial permafrost belt of the Qilian Mountains. Recent observations indicate ongoing permafrost degradation in this region. This study utilizes data from 255 observations provided by Sentinel-1 satellites, MODIS Land Surface Temperature, SMAP-L4 soil moisture data, GNSS measurements, and in situ measurement. We introduced Variational Bayesian independent Component Analysis (VB-ICA) in multi-temporal Interferometric Synthetic Aperture Radar (MT-InSAR) processing to investigate the spatial-temporal characteristics of surface deformation and permafrost active layer thickness (ALT) variations. The analysis demonstrates strong agreement with borehole data and offers improvements over traditional methodologies. The maximum value of ALT in the basin is found to be 5.7 m. VB-ICA effectively delineates seasonal deformations related to the freeze-thaw cycles, with a peak seasonal deformation amplitude of 60 mm. Moreover, the seasonal permafrost's lower boundary reaches an elevation of 3700 m, revealing that permafrost is experiencing widespread degradation and associated soil erosion in the high elevation region of The Heihe River Basin. The paper also explores the efficacy of reference point selection and baseline network establishment for employing the InSAR method in monitoring freeze-thaw deformations. The study underscores the InSAR method's adaptability and its importance for interpreting permafrost deformation and related parameters.

Rice encrusting with small‐seeded native species for reintroduction in agroecosystems: a case study in Lindernia procumbens

Seed coating is commonly applied in agricultural seed industry to alleviate biotic and edaphic barriers and improve seed germination, seedling emergence and establishment. Recently, this seed enhancement technology has been tested and applied to seeds of native species for ecological restoration and conservation. This work presents a novel application of seed coating for the reintroduction of species with dust‐like seeds that render direct seeding and cultivation unfeasible. Here we have used seed coating on Lindernia procumbens (Krocker) Philcox (Linderniaceae), a threatened annual species of paddy fields. Lindernia procumbens seeds were encrusted to the surface of rice seeds that acted as carrier to spread the species along rice sowing. We first tested how two selected concentrations of binder affected L. procumbens germination, then we investigated sowing depth (i.e. surface level—light, and buried—darkness) effect. Rice encrusting is a feasible and valuable tool for preserving threatened species with tiny seeds, since binder did not limit L. procumbens germination. Light increased L. procumbens seedlings emergence compared to buried conditions. Although L. procumbens emergence was limited in a paddy field trial, we promoted the formation of a soil seed bank for the species. As such, this should not discourage the possibility to reintroduce rare species with tiny seeds in agroecosystems. This pioneering technique can be extended to ecological restoration, where there is an urgent need for new seed‐based approaches and seed‐coating technologies to improve seedling establishment and restoration efficacy.

Genome wide screening to discover novel toxin-antitoxin modules in Mycobacterium indicus pranii; perspective on gene acquisition during mycobacterial evolution.

Mycobacterium indicus pranii (MIP), a benign saprophyte with potent immunomodulatory attributes, holds a pivotal position in mycobacterial evolution, potentially serving as the precursor to the pathogenic Mycobacterium avium complex (MAC). Despite its established immunotherapeutic efficacy against leprosy and notable outcomes in gram-negative sepsis and COVID-19 cases, the genomic and biochemical features of MIP remain largely elusive. This study explores the uncharted territory of toxin-antitoxin (TA) systems within MIP, hypothesizing their role in mycobacterial pathogenicity regulation. Genome-wide screening, employing diverse databases, unveils putative TA modules in MIP, setting the stage for a comparative analysis with known modules in Mycobacterium tuberculosis, Mycobacterium smegmatis, Escherichia coli, and Vibrio cholerae. The study further delves into the TA network of MAC and Mycobacterium intracellulare, unraveling interactive properties and family characteristics of identified TA modules in MIP. This comprehensive exploration seeks to illuminate the contribution of TA modules in regulating virulence, habitat diversification, and the evolutionary pathogenicity of mycobacteria. The insights garnered from this investigation not only enhance our understanding of MIP's potential as a vaccine candidate but also hold promise in optimizing tuberculosis drug regimens for expedited recovery.

Therapeutic Potential of Decoys for Prostate Cancers: A Review of Recent Updates.

Prostate cancer is ranked second among the most common male cancers. Androgen deprivation therapy (ADT) has long been the first-line treatment and the basis for all other therapies, reducing circulating androgens to castration levels and preventing disease development. Nevertheless, ADT monotherapy may not always limit disease development, and even at low testosterone levels, hormone-sensitive prostate cancer will become castration-resistant. Recent research demonstrates that prostate cancer can have a range of potentially actionable genetic abnormalities; no medications that target these variations have yet been shown to elicit therapeutic advantages. Despite their established efficacy in the management of other cancers, advanced genetic or immunological approaches are not regularly used to treat prostate cancer patients. As a result, there is an unmet demand for medicines that offer a better chance of survival than the existing castration- resistance prostate cancer (CRPC) therapy regimens. The use of oligodeoxynucleotides (ODN) and peptides in decoy technology have been developed as novel therapeutic approaches. Decoy ODNs bind to a particular transcription factor with high affinity and may suppress gene transcription. Peptide decoys bind to specific ligands with high specificity and inhibit signaling pathways. Recent evidence supports the notion that these techniques are promising and attractive in the fight against cancer. In the present review, we discuss the use of decoy technology as a novel therapeutic approach against prostate cancer.

Safety and efficacy of moderate-intensity statin plus ezetimibe versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease: A meta-analysis

Atherosclerotic cardiovascular disease (ASCVD), affects approximately 18.6 million individuals worldwide and poses a significant healthcare related challenge. Despite the established efficacy of both high-intensity statin monotherapy (HIS) and moderate-intensity statin plus ezetimibe (MIS+EZT) in ASCVD management, the optimal treatment strategy remains unclear. A thorough literature study was conducted across PubMed, Embase, and the Cochrane databases, focusing on studies that compared the effects of moderate-intensity statins plus ezetimibe with high-intensity statin monotherapy in ASCVD patients. In the 13 included studies, involving 8,592 patients, 4,525 (52.67 %) of which received moderate-intensity statin plus ezetimibe treatment. The follow-up period ranged from 4 to 156 weeks, with participant ages varying LDL-C from 55.2 to 71 years old. Analysis revealed significant MIS+EZT-associated with greater percentages of patients achieved the goal in Low-Density Lipoprotein (LDL-C) < 70 (Odds Ratio (OR) 1.76; 95 % CI [1.26; 2.45]; p = 0.001; I² = 73 %), LDL-C reduction (Mean Difference (MD) -5.05 mg/dL; 95 % CI [-9.02;-1.07]; p < 0.013; I² = 56 %;); Total Cholesterol reduction (MD -7.91 mg/ dL; 95 % CI [-14.90; -0.91]; p < 0.027; I² = 60 %); Triglycerides reduction (MD -8.20 mg/ dL; 95 % CI [-13.05; -3.35]; p < 0.001; I² = 2 %;); There was no statistical difference between groups in Drug Adverse reaction (Risk Ratio (RR) 1.19; 95 % CI [0.79; 1.78]; p = 0.404; I² = 0 %); and Drug intolerance (RR 0.78; 95 % CI [0.32; 1.92]; p = 0.584; I² = 35 %). This meta-analysis highlights the effectiveness of MIS+EZT in improving significant lipid profile components for ASCVD patients, as can been seen through the greater percentage of patients achieving the LDL-C < 70 mg/dL target and lower LDL-C, total cholesterol and triglycerides levels. Importantly, there were no significant differences in the occurrence of overall adverse events and adverse drug reactions between the two groups.

Psilocybin for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) stands as a formidable neurodegenerative ailment and a prominent contributor to dementia. The scarcity of available therapies for AD accentuates the exigency for innovative treatment modalities. Psilocybin, a psychoactive alkaloid intrinsic to hallucinogenic mushrooms, has garnered attention within the neuropsychiatric realm due to its established safety and efficacy in treating depression. Nonetheless, its potential as a therapeutic avenue for AD remains largely uncharted. This comprehensive review endeavors to encapsulate the pharmacological effects of psilocybin while elucidating the existing evidence concerning its potential mechanisms contributing to a positive impact on AD. Specifically, the active metabolite of psilocybin, psilocin, elicits its effects through the modulation of the 5-hydroxytryptamine 2A receptor (5-HT2A receptor). This modulation causes heightened neural plasticity, diminished inflammation, and improvements in cognitive functions such as creativity, cognitive flexibility, and emotional facial recognition. Noteworthy is psilocybin's promising role in mitigating anxiety and depression symptoms in AD patients. Acknowledging the attendant adverse reactions, we proffer strategies aimed at tempering or mitigating its hallucinogenic effects. Moreover, we broach the ethical and legal dimensions inherent in psilocybin's exploration for AD treatment. By traversing these avenues, We propose therapeutic potential of psilocybin in the nuanced management of Alzheimer's disease.

A randomized, double-blind, placebo-controlled trial to evaluate the effect of nabiximols oromucosal spray on clinical measures of spasticity in patients with multiple sclerosis

BackgroundSpasticity is a common and potentially debilitating symptom of multiple sclerosis (MS) with a highly variable presentation. Understanding, quantifying, and managing MS-associated spasticity (MSS) is a challenge for research and in clinical practice. The tetrahydrocannabinol:cannabidiol oromucosal spray nabiximols has demonstrated beneficial effects in the treatment of MSS in clinical studies as well as real-world observational studies, and is approved for the treatment of MSS in 29 countries globally. Most randomized studies evaluated the efficacy of nabiximols using the change in average daily spasticity scores reported by patients using the spasticity Numeric Rating Scale as a primary endpoint. This study, RELEASE MSS1 (NCT04657666), was conducted using a prespecified primary endpoint of change in spastic muscle tone (Modified Ashworth Scale Lower Limb Muscle Tone-6 [MAS LLMT-6]) to corroborate the efficacy of nabiximols as adjunctive therapy observed with the patient-measured spasticity Numeric Rating Scale primary endpoint in the previous pivotal studies. MethodsThis was a phase 3, multicenter, randomized, double-blind, placebo-controlled, 2-treatment, 2-period, crossover trial. Because of the prevalence and functional impact of lower limb spasticity on the individual patient's overall experience of MS spasticity, the MAS LLMT-6 was derived from the clinician-rated MAS. The MAS LLMT-6 is the average transformed MAS score of 6 muscle groups (knee flexors, knee extensors, and ankle plantar flexors; all assessed bilaterally). Secondary measures included MAS LLMT-4 scores, defined as the average of the 4 individual MAS-transformed scores of knee flexors and knee extensors bilaterally. Patients had a diagnosis of MS and an untransformed MAS score of at least 2 in ≥2 of 6 LLMT-6 muscle groups despite current treatment with ≥1 of the following oral antispasticity agents: baclofen, tizanidine, or dantrolene. Eligible participants were randomly assigned to 1 of 2 treatment sequences. Each treatment sequence consisted of two treatment periods, each consisting of a 14-day dose titration phase followed by a 7-day dose maintenance phase. ResultsOf 68 patients enrolled, 33 were assigned to nabiximols followed by placebo and 35 were assigned to placebo followed by nabiximols. Least squares mean changes in MAS LLMT-6 scores from baseline to day 21 were −0.23 for nabiximols and −0.26 for placebo; the least squares mean treatment difference in MAS LLMT-6 scores for nabiximols versus placebo was 0.04, which was not statistically significant (P = 0.7152). Mean changes in MAS LLMT-4 scores from baseline to day 21 also were not significantly different between the nabiximols and placebo groups. Safety results in this study were consistent with the known safety profile of nabiximols in patients with MSS. ConclusionDespite the established efficacy of nabiximols in MSS observed using patient-reported measures, the primary endpoint was not met in this study. The findings from this study reflect and emphasize some of the challenges in the evaluation and treatment of MS spasticity. Clinical trial registration number (ClinicalTrials.gov): NCT04657666

MEK Inhibition Enhances the Antitumor Effect of Radiotherapy in NF1-Deficient Glioblastoma.

Individuals with neurofibromatosis type 1, an autosomal dominant neurogenetic and tumor predisposition syndrome, are susceptible to developing low-grade glioma and less commonly high-grade glioma. These gliomas exhibit loss of the neurofibromin gene [neurofibromin type 1 (NF1)], and 10% to 15% of sporadic high-grade gliomas have somatic NF1 alterations. Loss of NF1 leads to hyperactive RAS signaling, creating opportunity given the established efficacy of MEK inhibitors in plexiform neurofibromas and some individuals with low-grade glioma. We observed that NF1-deficient glioblastoma neurospheres were sensitive to the combination of an MEK inhibitor (mirdametinib) with irradiation, as evidenced by synergistic inhibition of cell growth, colony formation, and increased cell death. In contrast, NF1-intact neurospheres were not sensitive to the combination, despite complete ERK pathway inhibition. No neurosphere lines exhibited enhanced sensitivity to temozolomide combined with mirdametinib. Mirdametinib decreased transcription of homologous recombination genes and RAD51 foci, associated with DNA damage repair, in sensitive models. Heterotopic xenograft models displayed synergistic growth inhibition to mirdametinib combined with irradiation in NF1-deficient glioma xenografts but not in those with intact NF1. In sensitive models, benefits were observed at least 3 weeks beyond the completion of treatment, including sustained phosphor-ERK inhibition on immunoblot and decreased Ki-67 expression. These observations demonstrate synergistic activity between mirdametinib and irradiation in NF1-deficient glioma models and may have clinical implications for patients with gliomas that harbor germline or somatic NF1 alterations.

A systematic review and meta-analysis to evaluate the diagnostic accuracy of PSMA PET/CT in the initial staging of prostate cancer.

Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging. Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI. A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies. The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies.

Comparative study on the establishment efficacy of four types of animal models of rectovaginal fistula in rabbits

Various surgical methods have so far been developed for treating rectovaginal fistula (RVF), each with its own advantages and disadvantages. The lack of standardized animal models of RVF is a major reason for the failure to establish a unified and effective surgical method for the treatment of RVF. This study aimed to explore the feasibility of an RVF animal model by magnetic compression and compare it with the traditional modeling method. Thirty-two female Japanese white rabbits were randomly divided into four groups: A, B, C, and D, based on how the rectovaginal septum was treated. The operation time, intraoperative blood loss, and model success rate of each group were determined. The experimental animals were euthanized 2 weeks after the operation. Their rectovaginal septum specimens were obtained. RVF was observed by the naked eye. The fistula size was measured. Histological changes of fistula were observed by hematoxylin and eosin and Masson staining. All rabbits completed the RVF model and survived 2 weeks after the operation. Groups A and B had no bleeding, while groups C and D had < 0.5 mL of bleeding. The magnet detached in 4–6 days in group A, while it remained in place for 2 weeks after surgery in group B. Only one group D rabbit had a plastic hose for 2 weeks after surgery. The RVFs of groups A and C healed by themselves. In group B, the fistula was well formed. In group D, fistula healing was observed in three animals and the diameter of the fistulas was only 2.82–4.64 mm in the other four animals. Groups B and D had a scar on the inner surface of fistulas. Our study shows that the magnetic compression technique based on the T-shaped magnet is a highly useful method to establishing a continuous and stable RVF model in rabbits.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation (ta-VNS) in the treatment of tinnitus: protocol for an updated systematic review and meta-analysis

IntroductionWith an increasing incidence and significant effects on patients, tinnitus has become a major disease burden. There is a dearth of therapies with established efficacy for tinnitus. Transcutaneous auricular vagus...

The Use of Biologic Agents for the Treatment of Cutaneous Immune-Related Adverse Events from Immune Checkpoint Inhibitors: A Review of Reported Cases.

Cutaneous immune-related adverse events encompass a spectrum of dermatological manifestations, including lichenoid reactions, psoriasiform eruptions, eczematous dermatitis, immunobullous disorders, granulomatous reactions, pruritus, vitiligo, and severe cutaneous adverse reactions such as Stevens-Johnson syndrome. The conventional approach to treating high-grade or refractory cutaneous immune-related adverse events has involved high-dose systemic corticosteroids. However, their use is limited owing to the potential disruption of antitumor responses and associated complications. To address this, corticosteroid-sparing targeted immunomodulators have been explored as therapeutic alternatives. Biologic agents, commonly employed for non-cutaneous immune-related adverse events such as colitis, are increasingly recognized for their efficacy in treating various patterns of cutaneous immune-related adverse events, including psoriasiform, immunobullous, and Stevens-Johnson syndrome-like reactions. This review consolidates findings from the English-language literature, highlighting the use of biologic agents in managing diverse cutaneous immune-related adverse event patterns, also encompassing maculopapular, eczematous, and lichenoid eruptions, pruritus, and transient acantholytic dermatosis (Grover disease). Despite the established efficacy of these agents, further research is necessary to explore their long-term effects on antitumor responses.

The when, why, and how of using glycopyrronium to diminish drooling in children with neurodevelopmental disabilities: Implications for clinical practice

BackgroundDespite the established efficacy of glycopyrronium bromide in reducing drooling among children with neurodevelopmental disabilities, evidence on its impact on the daily lives of children and parents and effectiveness in a real-world setting are scarce, especially among long-term users. This study explored timing and duration of glycopyrronium treatment, effect and impact on daily life, and occurrence of side effects to inform clinical practice. MethodsThis was a retrospective cohort study at a national referral centre for drooling, including 61 children with nonprogressive neurodevelopmental disabilities, treated with glycopyrronium for anterior and/or posterior drooling between 2011 and 2021. Data were obtained from medical records and supplemented by structured telephone interviews with parents. ResultsAnterior drooling severity decreased in 82% of the included children. Changes in the impact of drooling on burden of care, social interaction, and self-esteem were reported in 55%, 31%, and 36%, respectively. Side effects were noted for 71% of cases, yet only 36% of parents deemed these as outweighing the positive impact of treatment. A substantial majority (77%) of the included children were long-term users (≥6 months). Among these, 38% of parents reported decreasing effectiveness and 27% noticed more prominent side effects over time. ConclusionsGlycopyrronium demonstrated potential in mitigating the impact of drooling on daily life, although variations were observed in the specific aspects and extent of improvement. The real-world context of our study provides important insights for refining clinical practices, emphasizing the need for balanced consideration of treatment benefits and potential side effects to facilitate shared decision-making.