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PloS One 2024Autoimmune diseases affect 5-10% of the global population and cause chronic pain and impaired functionality. Chronic pain management involves pharmacological and...
BACKGROUND
Autoimmune diseases affect 5-10% of the global population and cause chronic pain and impaired functionality. Chronic pain management involves pharmacological and non-pharmacological interventions, with non-pharmacological options gaining attention as safe, effective, and cost-effective alternatives. However, further research is needed to determine the effectiveness of these therapies in African patients with autoimmune diseases, as existing evidence varies.
METHODS
This review protocol has been registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023449896). Electronic databases (PubMed, Africa Index Medicus, Cochrane Library, CINAHL, PsycINFO, and Web of Science) will be used for searching published articles. The study will use R for data synthesis, employing a random-effects meta-analysis approach to calculate pooled effect sizes, assess heterogeneity using the I2 statistic, and evaluate publication bias. In conclusion, this protocol aims to fill the knowledge gap on non-pharmacological therapies for chronic pain in patients with autoimmune diseases in Africa. It will potentially enhance evidence-based decision-making to improve pain management and, hence, the quality of life of people with autoimmune diseases in Africa.
Topics: Humans; Systematic Reviews as Topic; Chronic Pain; Autoimmune Diseases; Meta-Analysis as Topic; Africa; Pain Management; Quality of Life
PubMed: 38954682
DOI: 10.1371/journal.pone.0306564 -
PloS One 2024Uterine leiomyomas (often referred to as fibroids or myomas) are common benign, hormone-dependent tumors that grow in the uterus and occur in approximately 25% of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Uterine leiomyomas (often referred to as fibroids or myomas) are common benign, hormone-dependent tumors that grow in the uterus and occur in approximately 25% of reproductive age women, depending on selected population. Treatment recommendation is typically based on fibroid size, location, the patient's age, reproductive plans, and obstetrical history. Despite the range of treatment options available for uterine fibroids and their symptoms, including hysterectomy, myomectomy, endometrial ablation, endometrial uterine artery embolization, and magnetic resonance-guided focused-ultrasound surgery, myomectomy remains the gold standard treatment for patients who desire fertility-preserving surgery for their uterine fibroids. Myomectomy, while a prevalent surgical option for the removal of fibroids, carries known risks such as fibroid recurrence, symptom recurrence, and the subsequent need for reintervention. Despite ongoing research and advances in medical treatments for fibroids, there currently are no universally recommended therapeutic interventions proven to effectively delay the recurrence of fibroids or the return of symptoms following this procedure. This situation underscores a significant area of unmet medical need and highlights the importance of continued investigation into preventive strategies and long-term management options for patients undergoing fibroid removal with uterine preservation. We designed a study to assess the efficacy of the new FDA-approved GnRH antagonist, Myfembree in delaying the return of fibroids and their associated symptoms.
METHODS
A randomized, prospective, open-label clinical trial. The participants (n = 136) will be randomly distributed into two groups. The Control Group (Standard of care) will receive treatment with standard of care (SoC) after surgical myomectomy and the treatment group will receive Relugolix combination therapy (Myfembree®) after surgical myomectomy. The study protocol was approved by the University of Chicago's Institutional Review Board (IRB#22-0282), ensuring that all participants would provide written informed consent before their inclusion.
DISCUSSION
In this project, we propose the use of daily dosed Relugolix combination therapy (Relugolix with estradiol and norethindrone acetate), which is approved for uterine fibroids treatment, has the potential to delay the recurrence of fibroid symptoms, prolong the improved quality of life and delay need for re-intervention after uterine sparing surgery.
TRIAL REGISTRATION
The study protocol was approved by the Institutional Review Board of the University of Chicago on 9/16/2022 and was registered at ClinicalTrials.gov with number NCT05538689 on Sep 7, 2022. All subjects will provide informed consent to participate.
Topics: Humans; Female; Uterine Myomectomy; Leiomyoma; Standard of Care; Uterine Neoplasms; Adult; Middle Aged; Randomized Controlled Trials as Topic; Quality of Life
PubMed: 38954680
DOI: 10.1371/journal.pone.0306053 -
PloS One 2024In the southeastern United States, wood ducks (Aix sponsa) have historically experienced interspecific brood parasitism (IBP) primarily from hooded mergansers...
In the southeastern United States, wood ducks (Aix sponsa) have historically experienced interspecific brood parasitism (IBP) primarily from hooded mergansers (Lophodytes cucullatus), but the recent northward expansion of black-bellied whistling-ducks (Dendrocygna autumnalis) has added a new complexity to these interactions. We monitored nest boxes in Louisiana to evaluate the influence IBP had on wood duck daily nest survival rate (after, DSR) and duckling recruitment. We monitored 1,295 wood duck nests from 2020-2023 and found 112 (8.7%) were parasitized by hooded mergansers and 148 (11.5%) by whistling-ducks. Parasitic egg-laying by hooded mergansers lowered wood duck DSR, while DSR for nests parasitized by whistling-ducks was comparable to clutches containing only wood duck eggs. We considered the wood duck capture histories of 2,465 marked female ducklings and 540 banded adult females to estimate a duckling recruitment probability for the entire study period. We recaptured 50 ducklings as adults; 6 (12.0%) hatched from clutches parasitized by hooded mergansers, 1 (2.0%) from a clutch parasitized by a whistling-duck, and 43 (86.0%) from clutches containing only wood duck eggs. The duckling recruitment probability was 0.039 (95% credible interval = 0.028, 0.051). Nest initiation date had a negative effect on recruitment, wherein most recruits hatched from nests initiated earlier in the season. Given only ~9% of wood duck nests contained hooded merganser eggs, we conclude IBP writ large had no detrimental effect on DSR at a population level. The lower DSR of clutches parasitized by hooded mergansers is potentially linked to a high abundance of early-season parasites that produce "dump nests" and these clutches are often abandoned without being incubated. Despite ongoing parasitism by hooded mergansers and the range expansion of whistling-ducks, wood duck productivity in Louisiana appears to be minimally affected by interspecific brood parasitism.
Topics: Animals; Ducks; Nesting Behavior; Female; Louisiana
PubMed: 38954676
DOI: 10.1371/journal.pone.0305899 -
International Journal of Surgery... Jul 2024
PubMed: 38954671
DOI: 10.1097/JS9.0000000000001898 -
International Journal of Surgery... Jul 2024Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively...
Effect of carbon nanoparticle suspension injection versus indocyanine green tracer in guiding lymph node dissection during radical gastrectomy (FUTURE-01): a randomized clinical trial.
BACKGROUND
Carbon nanoparticle suspension injection (CNSI) and indocyanine green (ICG) have both been applied intraoperatively to facilitate lymphatic mapping and postoperatively to sort lymph nodes (LNs) in gastric cancer patients. However, no study has compared the two tracers in gastric cancer patients.
MATERIALS AND METHODS
This prospective randomized controlled trial was conducted from January 2022 to March 2023. Patients with potentially resectable gastric cancer (cT1-4a N0/+ M0) were randomized to the CNSI or ICG group.
RESULTS
This study enrolled 96 patients. Ninety patients were in the modified intention-to-treat population, including 46 patients (32 males and 14 females; mean [SD] age, 57.4 [9.4] years) in the CNSI group and 44 patients (31 males and 13 females; mean [SD] age, 60.8 [8.8] years) in the ICG group. The mean (SD) number of retrieved LNs was 69.8 (21.9) and 53.6 (17.2) in the CNSI and ICG groups, respectively (P<0.001). The mean (SD) number of retrieved micro-LNs was 19.9 (13.3) and 11.6 (9.9) in the CNSI and ICG groups, respectively (P=0.001). The mean (SD) number of metastatic LNs was 8.1 (11.9) and 5.2 (9.2) in the CNSI and ICG groups, respectively (P=0.19).
CONCLUSIONS
Compared with ICG, CNSI can increase the number of LNs detected, especially micro-LNs. Both tracers have high diagnostic value for detecting metastatic LNs. CNSI-guided lymphography may be a superior method for improving the accuracy of LN dissection.
PubMed: 38954670
DOI: 10.1097/JS9.0000000000001873 -
International Journal of Surgery... Jul 2024Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies...
BACKGROUND
Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies of urology, ChatGPT offers a novel possibility to aid in clinical decision-making. This study aimed to investigate the decision-making ability of LLMs in solving complex urology-related problems and assess its effectiveness in providing psychological support to patients with urological disorders.
MATERIALS AND METHODS
This study evaluated the clinical and psychological support capabilities of ChatGPT 3.5 and 4.0 in the field of urology. A total of 69 clinical and 30 psychological questions were posed to the AI models, and their responses were evaluated by both urologists and psychologists. As a control, clinicians from Chinese medical institutions provided responses under closed-book conditions. Statistical analyses were conducted separately for each subgroup.
RESULTS
In multiple-choice tests covering diverse urological topics, ChatGPT 4.0, performed comparably to the physician group, with no significant overall score difference. Subgroup analyses revealed variable performance, based on disease type and physician experience, with ChatGPT 4.0 generally outperforming ChatGPT 3.5 and exhibiting competitive results against physicians. When assessing the psychological support capabilities of AI, it is evident that ChatGPT4.0 outperforms ChatGPT3.5 across all urology-related psychological problems.
CONCLUSIONS
The performance of LLMs in dealing with standardized clinical problems and providing psychological support has certain advantages over clinicians. AI stands out as a promising tool for potential clinical aid.
PubMed: 38954666
DOI: 10.1097/JS9.0000000000001775 -
International Journal of Surgery... Jul 2024Liver failure remains a critical clinical challenge with limited treatment options. Cross-circulation, the establishment of vascular connections between individuals, has...
BACKGROUND
Liver failure remains a critical clinical challenge with limited treatment options. Cross-circulation, the establishment of vascular connections between individuals, has historically been explored as a potential supportive therapy but with limited success. This study investigated the feasibility of combining cross-circulation with a rapidly deployable veno-venous bypass (VVB) graft for multi-organ support in a rat model of total hepatectomy, representing the most severe form of liver failure.
MATERIALS AND METHODS
A Y-shaped VVB graft was fabricated using coaxial electrospinning of PLCL/heparin nanofibers and magnetic rings for rapid anastomosis. After total hepatectomy in rats, the VVB graft was implanted to divert blood flow. Cross-circulation was then established between anhepatic and normal host rats. Hemodynamics, biochemical parameters, blood gases, and survival were analyzed across three groups: hepatectomy with blocked vessels (block group), hepatectomy with VVB only (VVB group), and hepatectomy with VVB and cross-circulation (VVB/cross-circulation group).
RESULTS
The VVB graft exhibited suitable mechanical properties and hemocompatibility. VVB rapidly restored hemodynamic stability and mitigated abdominal congestion post-hepatectomy. Cross-circulation further ameliorated liver dysfunction, metabolic derangements, and coagulation disorders in anhepatic rats, significantly prolonging survival compared to the VVB group (mean 6.56±0.58 vs 4.05±0.51 h, P<0.05) and the block group (mean 1.01±0.05 h, P<0.05).
CONCLUSION
Combining cross-circulation with a rapidly deployed VVB graft provided effective multi-organ biosystemic support in a rat model of total hepatectomy, substantially improving the biochemical status and survival time. This approach holds promise for novel liver failure therapies and could facilitate liver transplantation procedures.
PubMed: 38954664
DOI: 10.1097/JS9.0000000000001923 -
Expert Opinion on Pharmacotherapy Jul 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, and... (Review)
Review
INTRODUCTION
Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by hepatic steatosis and cardiometabolic risk factors like obesity, type 2 diabetes, and dyslipidemia. Persistent metabolic injury may promote inflammatory processes resulting in metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Mechanistic insights helped to identify potential drug targets, thereby supporting the development of novel compounds modulating disease drivers.
AREAS COVERED
The U.S. Food and Drug Administration has recently approved the thyroid hormone receptor β-selective thyromimetic resmetirom as the first compound to treat MASH and liver fibrosis. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. Lessons learned from terminated clinical trials are discussed together with the first results of trials investigating novel combinational therapeutic approaches.
EXPERT OPINION
Approval of resmetirom as the first anti-MASH agent may revolutionize the therapeutic landscape. However, long-term efficacy and safety data for resmetirom are currently lacking. In addition, heterogeneity of MASLD reflects a major challenge to define effective agents. Several lead compounds demonstrated efficacy in reducing obesity and hepatic steatosis, while anti-inflammatory and antifibrotic effects of monotherapy appear less robust. Better mechanistic understanding, exploration of combination therapies, and patient stratification hold great promise for MASLD therapy.
PubMed: 38954663
DOI: 10.1080/14656566.2024.2374463 -
International Journal of Surgery... Jul 2024
PubMed: 38954661
DOI: 10.1097/JS9.0000000000001918 -
Brain : a Journal of Neurology Jul 2024The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action...
The ability to initiate volitional action is fundamental to human behaviour. Loss of dopaminergic neurons in Parkinson's disease is associated with impaired action initiation, also termed akinesia. Both dopamine and subthalamic deep brain stimulation (DBS) can alleviate akinesia, but the underlying mechanisms are unknown. An important question is whether dopamine and DBS facilitate de novo build-up of neural dynamics for motor execution or accelerate existing cortical movement initiation signals through shared modulatory circuit effects. Answering these questions can provide the foundation for new closed-loop neurotherapies with adaptive DBS, but the objectification of neural processing delays prior to performance of volitional action remains a significant challenge. To overcome this challenge, we studied readiness potentials and trained brain signal decoders on invasive neurophysiology signals in 25 DBS patients (12 female) with Parkinson's disease during performance of self-initiated movements. Combined sensorimotor cortex electrocorticography (ECoG) and subthalamic local field potential (LFP) recordings were performed OFF therapy (N = 22), ON dopaminergic medication (N = 18) and ON subthalamic deep brain stimulation (N = 8). This allowed us to compare their therapeutic effects on neural latencies between the earliest cortical representation of movement intention as decoded by linear discriminant analysis classifiers and onset of muscle activation recorded with electromyography (EMG). In the hypodopaminergic OFF state, we observed long latencies between motor intention and motor execution for readiness potentials and machine learning classifications. Both, dopamine and DBS significantly shortened these latencies, hinting towards a shared therapeutic mechanism for alleviation of akinesia. To investigate this further, we analysed directional cortico-subthalamic oscillatory communication with multivariate granger causality. Strikingly, we found that both therapies independently shifted cortico-subthalamic oscillatory information flow from antikinetic beta (13-35 Hz) to prokinetic theta (4-10 Hz) rhythms, which was correlated with latencies in motor execution. Our study reveals a shared brain network modulation pattern of dopamine and DBS that may underlie the acceleration of neural dynamics for augmentation of movement initiation in Parkinson's disease. Instead of producing or increasing preparatory brain signals, both therapies modulate oscillatory communication. These insights provide a link between the pathophysiology of akinesia and its' therapeutic alleviation with oscillatory network changes in other non-motor and motor domains, e.g. related to hyperkinesia or effort and reward perception. In the future, our study may inspire the development of clinical brain computer interfaces based on brain signal decoders to provide temporally precise support for action initiation in patients with brain disorders.
PubMed: 38954651
DOI: 10.1093/brain/awae219