Relevant Clinical Evidence Research Articles

Chemotherapy affects the development of pathological scarring after general thoracic surgery in children.

Globally, a great number of children have been suffering from physical dysfunction and psychological stress due to uncontrollable scar growth and a lack of effective modalities. Despite chemotherapy's established role as a primary treatment for pathological scarring in adults, its efficacy in preventing or minimizing scar formation in paediatric patients remains underexplored. This retrospective cohort study aimed to refine the relevant clinical evidence and investigate the effect of chemotherapy on pathological scars in children. In this single-centre retrospective cohort study, the data of children aged ≤18 years who underwent thoracic surgery at the Children's Hospital of Fudan University between 1 January 2018, and 31 December 2021 were assessed. The primary outcome was pathological scarring, and the secondary outcomes were subjective symptoms accompanying pathological scarring, such as pain and itching. To mitigate indication bias, analysis was performed by inverse probability weighting (IPTW) log-binomial regression models. The cohort comprised 102 children, among whom 36 received adjuvant chemotherapy perioperatively, while 66 did not. Under the IPTW model, a statistically significant difference in pathological scarring incidence was observed between the chemotherapy and non-chemotherapy groups (16.7% vs. 29.4%, p = 0.027). And the children received chemotherapy post-operatively had a lower relative risk of pathological scarring, compared with those received chemotherapy both before and after surgery (19.8% vs. 28.8%). Adjuvant chemotherapy treatment after surgery may reduce the incidence of post-operative pathological scarring in children.

Sedaconda ACD-S for Sedation with Volatile Anaesthetics in Intensive Care: A NICE Medical Technologies Guidance.

Intensive care unit (ICU) patients receive highly complex care and often require sedation as part of their management. ICU sedation has traditionally been delivered using intravenous (IV) agents due to the impractical use of anaesthetic machines in this setting, which are used to deliver volatile sedation. Sedaconda anaesthetic conserving device (ACD)-S (previously known as AnaConDa-S) is a device which allows for the delivery of volatile sedation via the majority of mechanical ventilators by being inserted in the breathing circuit where the heat and moisture exchanger is normally placed. The National Institute of Health and Care Excellence (NICE), as part of the Medical Technologies Evaluation Programme, considered the potential benefits of using Sedaconda ACD-S compared to standard IV sedation in ICU patients. Here we describe the evidence evaluation undertaken by NICE on this technology, supported by CEDAR. CEDAR considered the evidence present in 21 publications that compared the clinical outcomes of patients receiving Sedaconda ACD-S-delivered sedation and IV sedation, and critiqued the economic model provided by the manufacturer. Clinical expert input during the evaluation process was used extensively to ensure that the relevant clinical evidence was captured and that the economic model was suitable for the UK setting. Due to the uncertainty of the evidence, sensitivity analysis was carried out on the key economic inputs to ensure the reliability of the results. Economic modelling has shown that Sedaconda ACD-S-delivered isoflurane sedation is cost saving on a 30-day horizon compared to IV sedation by £3833.76 per adult patient and by £2837.41 per paediatric patient. Clinical evidence indicated that Sedaconda ACD-S-delivered isoflurane sedation is associated with faster patient wake-up times than standard of care. Consequently, NICE recommended Sedaconda ACD-S as an option for delivering sedation in the ICU setting, but noted that further research should inform whether Sedaconda ACD-S-delivered sedation is of benefit to any particular subgroup of patients.

Propofol total intravenous anesthesia vs. sevoflurane inhalation anesthesia: Effects on post‑operative cognitive dysfunction and inflammation in geriatric patients undergoing laparoscopic surgery.

Propofol total intravenous anesthesia (TIVA) or sevoflurane inhalation anesthesia (IA) affects post-operative cognitive dysfunction in geriatric patients undergoing laparoscopic surgery; however, relevant real-world clinical evidence on the matter is limited. The present study aimed to compare the effects of propofol TIVA and sevoflurane IA on post-operative cognitive dysfunction in the aforementioned type of patients. The present prospective study enrolled 197 geriatric patients undergoing laparoscopic surgery. Patients were assigned to the propofol TIVA group (n=97) and sevoflurane IA group (n=100) according to the actual anesthesia regimens. The mini-mental state examination (MMSE) score was assessed before surgery and on day (D)1, D3 and D7 following surgery in both groups. The MMSE score on D1 was higher in the TIVA group compared with the IA group (P=0.006). The change in the MMSE scores from before surgery to D1 (P<0.001), D3 (P=0.011) and D7 (P=0.003) was smaller in the TIVA group vs. the IA group. Multivariate linear regression analyses suggested that the anesthesia method of TIVA (vs. IA) was independently related to the increased MMSE score on D1 (b=0.803; P=0.001) and D7 (b=0.472; P=0.025). The levels of interleukin (IL)-17A, IL-6 and tumor necrosis factor-α on D1, D3 and D7 exhibited a slightly decreasing trend in the TIVA group vs. the IA group, although the difference was not statistically significant (all P>0.05). Notably, the levels of IL-17A before surgery (P=0.015), on D3 (P=0.016) and D7 (P=0.002), as well as those of IL-6 on D1 (P=0.027), were negatively associated with the MMSE score at the corresponding time points. Overall, the present study demonstrates that propofol TIVA ameliorates post-operative cognitive dysfunction on D1 compared with sevoflurane IA and exerts a potentially suppressive effect on inflammation in geriatric patients undergoing laparoscopic surgery.

Economic value of diastasis repair with the use of mesh compared to no intervention in Italy

AimRectus abdominal diastasis (RAD) can cause mainly incontinence and lower-back pain. Despite its high incidence, there is no consensus regarding surgical indication. We aimed at comparing RAD repair (minimally invasive technique with mesh implant) with no treatment (standard of care – SOC) through cost-effectiveness and budget impact analyses from both National Healthcare Service (NHS) and societal perspectives in Italy.MethodsA model was developed including social costs and productivity losses derived by the online administration of a socio-economic questionnaire, including the EuroQol for the assessment of quality of life. Costs for the NHS were based on reimbursement tariffs.ResultsOver a lifetime horizon, estimated costs were 64,115€ for SOC and 46,541€ for RAD repair in the societal perspective; QALYs were 19.55 and 25.75 for the two groups, respectively. Considering the NHS perspective, RAD repair showed an additional cost per patient of 5,104€ compared to SOC, leading to an ICUR of 824€. RAD repair may be either cost-saving or cost-effective compared to SOC depending on the perspective considered. Considering a current scenario of 100% SOC, an increased diffusion of RAD repair from 2 to 10% in the next 5 years would lead to an incremental cost of 184,147,624€ for the whole society (87% borne by the NHS) and to incremental 16,155 QALYs.ConclusionIn light of the lack of economic evaluations for minimally invasive RAD repair, the present study provides relevant clinical and economic evidence to help improving the decision-making process and allocating scarce resources between competing ends.

Approach to chronic wrist pain in adults: Review of common pathologies for primary care practitioners.

To develop an approach for identifying, investigating, and initially managing common causes of chronic wrist pain seen by primary care practitioners. Relevant clinical evidence and literature were identified using the PubMed database. Chronic wrist pain is a common presentation in the primary care setting. The complex anatomy of the wrist leads to a broad differential diagnosis. Elements of history, findings of physical examinations and investigations, and management relevant to the following pathologies are discussed, including scaphoid fracture nonunion, thumb carpometacarpal joint osteoarthritis, scapholunate ligament instability, triangular fibrocartilage complex injuries, de Quervain tenosynovitis, extensor carpi ulnaris tendinopathy, carpal tunnel syndrome, and ganglion cysts. When evaluating chronic wrist pain, diagnostic imaging with x-ray scans can serve as an important ancillary investigation tool but should not override clinical suspicion. Advanced imaging (computed tomography or magnetic resonance imaging) is generally best ordered by a hand surgeon when it will help clarify a diagnosis and guide treatment. Chronic wrist pain is a functionally limiting problem best managed with timely diagnosis and treatment. A thorough history and physical examination are the cornerstones of an effective evaluation. When diagnosis is delayed, some wrist pathologies can lead to relatively poor outcomes, such as a scaphoid fracture nonunion resulting in diffuse wrist osteoarthritis.

Stellate ganglion, inflammation, and arrhythmias: a new perspective on neuroimmune regulation.

Current research on the stellate ganglion (SG) has shifted from merely understanding its role as a collection of neurons to recognizing its importance in immune regulation. As part of the autonomic nervous system (ANS), the SG plays a crucial role in regulating cardiovascular function, particularly cardiac sympathetic nerve activity. Abnormal SG function can lead to disordered cardiac electrical activity, which in turn affects heart rhythm stability. Studies have shown that excessive activity of the SG is closely related to the occurrence of arrhythmias, especially in the context of inflammation. Abnormal activity of the SG may trigger excessive excitation of the sympathetic nervous system (SNS) through neuroimmune mechanisms, thereby increasing the risk of arrhythmias. Simultaneously, the inflammatory response of the SG further aggravates this process, forming a vicious cycle. However, the causal relationship between SG, inflammation, and arrhythmias has not yet been fully clarified. Therefore, this article deeply explores the key role of the SG in arrhythmias and its complex relationship with inflammation, providing relevant clinical evidence. It indicates that interventions targeting SG function and inflammatory responses have potential in preventing and treating inflammation-related arrhythmias, offering a new perspective for cardiovascular disease treatment strategies.

PP93 Health Technology Assessments For Rare Diseases In Australia: A Case Study On Cystic Fibrosis

IntroductionCurrently, no cure exists for the 1 in 2,500 Australian babies born with potentially fatal cystic fibrosis (CF). The authors conducted a health technology assessment (HTA) case study analysis of all regulatory approved CF treatments in Australia from January 1994 to July 2022. Submissions were also made under the Therapeutics Goods Administration and Pharmaceutical Benefits Advisory Committee (TGA-PBAC) parallel process.MethodsPublic summary and source materials were researched to understand relevant clinical and health economic evidence requirements, and access decisions from Australia’s lead HTA body, PBAC.ResultsThe review found that there are more than seven approved products in Australia. Of those, all four novel CF transmembrane conductance regulator (CFTR) modulating medications, which treat the underlying disease, received an orphan drug designation and were eventually listed. However, initial HTA decisions were mixed, with one recommended (25%), one not recommended (25%), and two deferred (50%). Clinical efficacy, cost-effectiveness, clinical need, as well as patient/carer-centric perspectives were most influential in HTA recommendations. Like other rare disease treatments, price, high incremental cost-effectiveness ratios (ICERs), uncertainty around cost-effectiveness and/or efficacy were key barriers to positive decisions. Notably, Australian stakeholders did not recommend CF medicines when their ICERs significantly exceeded a threshold of AUD200,000 (USD134,700) per quality-adjusted life year (QALY) gained. Administratively, Australia addresses risks associated with poor cost-effectiveness and high costs through managed access programs, risk-sharing agreements (RSA) and special pricing arrangements.Recently approved elexacaftor-tezacaftor-ivacaftor would be inaccessible to many Australian patients without inclusion in the Pharmaceutical Benefits Scheme (PBS); this placement increases access by limiting patients’ payments to AUD42.50 (USD28.62) maximum per prescription. Alternatively, manufacturers of therapies for other chronic or rare life-threatening conditions can participate in Australia’s Highly Specialised Drugs Program and/or Life Saving Drugs Program to facilitate access.ConclusionsCompanies can accelerate and optimize market access by using the TGA-PBAC parallel process. Other Asia-Pacific countries can model components of Australia’s approach to advancing access to innovative, live-saving therapies.

Clinical Study on the Efficacy and Safety of Peg Rhg CSF for Autologous Hematopoietic Stem Cell Mobilization in Lymphoma and Multiple Myeloma：a Randomized Controlled, Multicenter Clinical Study

Introduction: PEG rhG CSF has been widely used in the prevention and treatment of bone marrow suppression after chemotherapy for a variety of tumors, but whether it can be used for lymphoma and Multiple myeloma autologous hematopoietic stem cell mobilization has no relevant clinical evidence. Therefore we carried out this randomized controlled, multicenter clinical study to evaluate the efficiency and safety of PEG-rhG-CSF in the mobilization of autologous hematopoietic stem cells for lymphoma and Multiple myeloma. Methods:This experiment selected an appropriate mobilization based on the patient's willingness and physical condition of the subjects. Chemotherapy mobilized patients underwent bone marrow mobilization when white blood cells reached their lowest point and began to rebound. The experimental group received a fixed dose of 12mg of polyethylene glycol recombinant human granulocyte stimulating factor injection (PEG-rhG-CSF) for mobilization; the control group received recombinant human granulocyte stimulating factor (rhG-CSF) 5-10μg/kg daily. Collect blood and bone marrow samples from patients daily and test white blood cells and CD34+cells every day. Record CD34+cells proportion until its qantity reached 2×10 6 proportion. The interval from mobilization to collection, the time for hematopoietic reconstruction after transplantation, and complications were also collected. Results : A total of 60 patients were included in this study, including 31 in the experimental group and 29 in the control group. There were no statistically significant differences in gender, age, disease classification, and pre harvest CD34+levels between the two groups of patients. The CD34+cells collected from both the experimental and control groups reached ≥ 2.0×10 6/kg and there was no statistically significant difference (Figure 1). There was no statistical difference between the experimental group and the control group in terms of CD34+cell collection frequency, CD34+cell count, interval from mobilization to collection time, neutrophil reconstruction time, and platelet reconstruction time. In terms of related side effects there was no statistically significant difference in the incidence of rash, fever, infection, and diarrhea between the two groups of patients. The incidence of bone pain in all patients was 15% (9/60), with 8 cases being mild and only 1 case being moderate. There was no significant statistical difference in the incidence of bone pain between the experimental group and the control group (Table 1). Conclusion : PEG-rhG-CSF is safe and effective for autologous hematopoietic stem cell mobilization in lymphoma and Multiple myeloma, and its efficacy is consistent with that of rhG CSF. However, the subcutaneous injection of rhG CSF is less frequent, which is easier for patients to accept. [Key words] PEG rhG CSF; matopoietic stem cell mobilization;ymphoma and Multiple myeloma; inical study

A Systematic Literature Review (SLR) and Meta-Analysis of Clinical Evidence of Second Line or Later (2L+) Treatments for Follicular Lymphoma (FL) in Adult Patients

Background:First-line (1L)standard of care (SOC) options for patients with FL include an anti-CD20 monoclonal antibody with or without chemotherapy, and second-line (2L) therapeutic options are similar to 1L. There is no defined SOC for patients who require treatment in third, fourth, and later lines of therapy (LOT). Additionally, patients with high-risk FL who relapse ≤ 24 months after frontline treatment (POD24) have limited treatment options that can provide a durable response. Recently, novel treatments such as CAR T cell therapies and T cell engager regimens have been shown to improve efficacy outcomes in third line or later (3L+) and POD24 populations. We conducted an SLR of all relevant clinical evidence to evaluate the efficacy and safety of available therapies used in the treatment of adult patients with R/R FL in 3L+, fourth line or later (4L+), and 2L+ POD24 settings. We also aimed to conduct meta-analyses to derive pooled effect estimates for response and survival outcomes in these settings. Methods: Publications from 01/01/1998 to 09/17/2022 were identified using Ovid MEDLINE ®, Embase, and Cochrane Central Register of Controlled Trials, with supplemental hand searches of key conferences and bibliographies of recent relevant SLRs. Study eligibility was assessed according to prespecified population, intervention, comparator, outcome, and study design criteria. Studies were eligible if they were in English and enrolled patients with R/R FL (grade 1‒3A) in 3L+, 4L+, and POD24 settings. Eligible treatments included CAR T cell therapies (axicabtagene ciloleucel, lisocabtagene maraleucel, and tisagenlecleucel), T cell engagers (mosunetuzumab, glofitamab, epcoritamab, odronextamab), phosphatidylinositol 3-kinase (PI3K) inhibitors (copanlisib, duvelisib, idelalisib), HSCT, yttrium-90 (90Y) ibritumomab tiuxetan, tazemetostat, and conventional therapies (immunochemotherapies, single- or multiagent chemo- or immunotherapies, and alkylating agents). Outcomes of interest were OS, PFS, ORR, CR rate, PR, duration of response, and time to next treatment. Independent review committee (IRC) data were extracted when both IRC- and investigator-assessed data were reported. Pooled estimates for ORR, CR rate, OS, and PFS across all treatments were calculated among 3L+, 4L+, and POD24 patient populations. For POD24 studies, we combined POD24 definitions (ie, definitions with respect to POD24 from frontline therapy or baseline) and POD24 patients across LOTs (ie, presenting in 2L+). For each outcome in 3L+, 4L+, and POD24 settings, ≥ 4 sufficiently similar studies were required for a meta-analysis to be deemed feasible. Results: Of 5250 records screened, 112 were included, representing 60 unique studies. Of 60 studies, 33 (55%) were retrospective or prospective observational, while 27 (45%) were clinical trials (randomized, nonrandomized, and single arm). There was significant heterogeneity in patient populations and baseline characteristics across studies. Most studies (n = 48; 80%) reported findings for 3L+ FL, with limited evidence for 4L+ and POD24 patients. Results for ORR, CR rate, PFS, and OS by treatment type across 3L+, 4L+, and POD24 patients are presented in Table 1. ORR and CR rate data were highly variable depending on treatment used and length of follow-up period in the study. Across 3L+, 4L+, and POD24 patients, the highest ORR and CR rate ranges were observed for CAR T cell therapies, T cell engagers, and HSCT. Median PFS was highest for HSCT, T cell engagers, and CAR T cell therapy in the 3L+ setting and was not reported or not reached for HSCT and T cell engagers in 4L+ and POD24 settings. Median OS was not reached for patients receiving T cell engagers in the 3L+ setting or those receiving CAR T cell therapy in the 3L+, 4L+, and POD24 settings. Various meta-analyses including all treatments were considered feasible for 3L+, 4L+, and POD24 populations (Table 2). For ORR and CR rate in the 3L+ population, sensitivity analyses excluding CAR T cell therapies, T cell engager regimens, and HSCT were feasible and showed lower ORR and CR rate when these therapies were removed. Conclusions: This SLR demonstrated an evolving FL treatment landscape, with new agents such as CAR T cell therapies and T cell engagers exhibiting potential for improving effectiveness of treatment for patients in 3L+, 4L+, and 2L+ POD24 populations.

The Impact of Menopause on Cardiovascular Aging: A Comprehensive Review of Androgen Influences.

Menopause represents a critical life stage in women, characterized by hormonal changes that significantly impact cardiovascular health. While the decline in estrogen levels has long been recognized as a major contributor to cardiovascular aging in menopausal women, the role of androgens, particularly testosterone, has gained increasing attention in recent years. This comprehensive review aims to provide a thorough understanding of the impact of menopause on cardiovascular aging, with a specific focus on the influences of androgens. A literature search was conducted to gather relevant studies and clinical evidence exploring the relationship between menopause, androgens, and cardiovascular health. The review integrates findings from various studies to present a holistic view of the topic. The review outlines the changes in hormone levels during menopause and discusses the cardiovascular risk factors associated with this transition. Furthermore, it explores the impact of menopause on cardiovascular structure and function, elucidating the underlying mechanisms that contribute to cardiovascular aging. Androgens' significance in maintaining cardiovascular homeostasis is discussed, followed by exploring the effects of androgen decline during menopause on lipid profiles, insulin sensitivity, vascular function, and other cardiovascular parameters. The review delves into the mechanisms of androgen action on the cardiovascular system, emphasizing the role of androgen receptors and the intricate interplay between androgens, estrogens, and other hormones. Clinical evidence supporting the effects of androgens on cardiovascular aging is presented, including studies investigating the association between androgen levels and cardiovascular outcomes. Additionally, the impact of androgen replacement therapy (ART) on cardiovascular risk markers and events in menopausal women is examined, along with controversies and conflicting findings surrounding the use of androgen therapy in cardiovascular aging. This structured review provides a comprehensive understanding of the impact of menopause on cardiovascular aging, with a specific focus on the role of androgens. By highlighting the significance of androgens in cardiovascular health during menopause, this review aims to create an initial impression and interest among readers, inviting potential citations in the future. The findings underscore the need for further research and offer insights into managing cardiovascular aging in menopausal women, including lifestyle interventions, pharmacological approaches, and the potential role of personalized medicine and precision therapies.

Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome.

Antibiotic use is associated with development of antimicrobial resistance and dysregulation of the microbiome (the overall host microbial community). These changes have in turn been associated with downstream adverse health outcomes. This review analyses recent important publications in a rapidly evolving field, contextualizing the available evidence to assist clinicians weighing the potential risks of antibiotics on a patient's microbiome. Although the majority of microbiome research is observational, we highlight recent interventional studies probing the associations between antibiotic use, microbiome disruption, and ill-health. These studies include germ-free mouse models, antibiotic challenge in healthy human volunteers, and a phase III study of the world's first approved microbiome-based medicine. The growing body of relevant clinical and experimental evidence for antibiotic-mediated microbiome perturbation is concerning, although further causal evidence is required. Within the limits of this evidence, we propose the novel term 'microbiotoxicity' to describe the unintended harms of antibiotics on a patient's microbiome. We suggest a framework for prescribers to weigh microbiotoxic effects against the intended benefits of antibiotic use.

The Effect of Very-Long-Chain n-3 Polyunsaturated Fatty Acids in the Central Nervous System and Their Potential Benefits for Treating Alcohol Use Disorder: Reviewing Pre-Clinical and Clinical Data.

Alcohol use poses a significant global health concern, leading to serious physical and socioeconomic issues worldwide. The current treatment options for problematic alcohol consumption are limited, leading to the exploration of alternative approaches, such as nutraceuticals. One promising target is very-long-chain n-3 polyunsaturated fatty acids (VLC n-3 PUFAs). This review aims to compile the most relevant pre-clinical and clinical evidence on the effect of VLC n-3 PUFAs on alcohol use disorders and related outcomes. The findings suggest that VLC n-3 PUFAs may alleviate the physiological changes induced by alcohol consumption, including neuroinflammation and neurotransmitter dysregulation. Additionally, they can reduce withdrawal symptoms, improve mood, and reduce stress level, all of which are closely associated with problematic alcohol consumption. However, more research is required to fully understand the precise mechanisms by which VLC n-3 PUFAs exert their function. Furthermore, PUFAs should not be considered a standalone solution, but as a complement to other therapeutic approaches. Although preliminary evidence supports the potential therapeutic effect of VLC n-3 PUFAs on problematic alcohol consumption, additional research is needed to validate these findings and determine the optimal use of PUFAs as part of a comprehensive approach to the treatment of alcohol use disorders.

An EHR Data Quality Evaluation Approach Based on Medical Knowledge and Text Matching

Introduction: Recently, medical artificial intelligence based on Electronic Health Records (EHR) is a significant research field, and EHR data has been widely used in clinical decision support systems and medical diagnosis systems. However, because EHR are used to record the patient's disease information and are not primarily designed for research and discovery, the utility of EHR for research will be hindered by data quality problems. Therefore, it is a meaningful and challenging task to evaluate the data quality of EHR before they are used in medical artificial intelligence. Most of the current EHR data quality evaluation methods are based on some conventional evaluation indicators, and rarely consider the introduction of clinical evidence.Materials and methods: we propose an EHR data quality evaluation approach based on clinical evidence and a deep text matching model. First, based on the medical knowledge of the particular disease, we establish the list of standard clinical evidence descriptions including typical symptoms and special signs, etc. Then we find the relevant clinical evidence from the EHR based on the text matching model, and finally evaluate the quality of the EHR based on the quantity and quality of the relevant clinical evidence found.Results: The experimental results of more than 1,000 EHR for two types of diseases show that our approach can effectively distinguish high-quality EHR from low-quality EHR, and the high-quality EHR found generally contains sufficient and consistent information related to disease diagnosis.Conclusions: Experiments results on a real-world dataset demonstrate the effectiveness of our EHR data quality evaluation approach based on medical knowledge and text matching.

Applications of Pulsed Electromagnetic Field Therapy in Skeletal-Muscle System: An Integrative Review

Background: The Pulsed Electromagnetic Field (PEMF) technology has attracted increasing interest since consistent evidence of its therapeutic properties has been demonstrated to treat musculoskeletal conditions. However, this technology is not new, and has already been used in different experimental models and clinical studies for the treatment of tendinopathies, osteoarthritis, increased cell proliferation, bone consolidation, among others. Methods: In this work, we carried out an integrative review of clinical and experimental studies published in the last twenty years, on the available scientific evidence that demonstrate the effects of PEMF in different applications for health treatments. Five databases including Medline, Pubmed Central, Scopus, Lilacs and PEDro were searched for studies from 2001 to September 2022. The results were analyzed by the team of researchers and clinical professionals to assure methodological quality of the studies for the elaboration of the theoretical review on the effects of electromagnetic field stimulation on skeletal muscles, tendon or bones. Results: Sixty-two studies were included in this review, presenting evidence of the biological effects of PEMF that can suggest it´s possible use to treat different disorders. Conclusions: Pulsed electromagnetic fields (PEMF) present relevant clinical and experimental evidence of beneficial effects in the treatment of several musculoskeletal inflammatory disorders, such as tendinopathies and osteoarthritis, in addition to the treatment of urinary incontinence and abdominal diastasis. PEMF can be considered as the evolution of electrical currents for the treatment of musculoskeletal disorders, mainly due to its better tolerance by patients.

Wireless technologies, non-ionizing electromagnetic fields and children: Identifying and reducing health risks

Children today are conceived and live in a sea of wireless radiation that did not exist when their parents were born. The launch of the digital age continues to transform the capacity to respond to emergencies and extend global communications. At the same time that this increasingly ubiquitous technology continues to alter the nature of commerce, medicine, transport and modern life overall, its varied and changing forms have not been evaluated for their biological or environmental impacts. Standards for evaluating radiation from numerous wireless devices were first set in 1996 to avoid heating tissue and remain unchanged since then in the U.S. and many other nations. A wide range of evidence indicates that there are numerous non-thermal effects from wireless radiation on reproduction, development, and chronic illness. Many widely used devices such as phones and tablets function as two-way microwave radios, sending and receiving various frequencies of information-carrying microwave radiation on multiple simultaneously operating antennas. Expert groups advising governments on this matter do not agree on the best approaches to be taken. The American Academy of Pediatrics recommends limited screen time for children under the age of two, but more than half of all toddlers regularly have contact with screens, often without parental engagement. Young children of parents who frequently use devices as a form of childcare can experience delays in speech acquisition and bonding, while older children report feelings of disappointment due to 'technoference'-parental distraction due to technology. Children who begin using devices early in life can become socially, psychologically and physically addicted to the technology and experience withdrawal upon cessation. We review relevant experimental, epidemiological and clinical evidence on biological and other impacts of currently used wireless technology, including advice to include key questions at pediatric wellness checkups from infancy to young adulthood. We conclude that consistent with advice in pediatric radiology, an approach that recommends that microwave radiation exposures be As Low As Reasonably Achievable (ALARA) seems sensible and prudent, and that an independently-funded training, research and monitoring program should be carried out on the long term physical and psychological impacts of rapidly changing technological milieu, including ways to mitigate impacts through modifications in hardware and software. Current knowledge of electrohypersensitivity indicates the importance of reducing wireless exposures especially in schools and health care settings.

Effect of β-blocker on patients with moderate functional mitral regurgitation undergoing surgical aortic valve replacement.

The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of β-blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post-operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. In this single-centre cohort study, patients who underwent isolated SAVR and complicated with pre-operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan-Meier method and tested by the log-rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between-group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all-cause death, repeat heart valve surgery, non-fatal myocardial infarction, stroke, and hospitalization for heart failure. A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2±12.2years. Eighty (48.5%) patients received post-operative BB therapy. The median follow-up time was 18.4months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29-1.62, P=0.388] or all-cause death (HR: 1.03, 95% CI: 0.30-0.56, P=0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31-1.97, P=0.607) and all-cause death (HR: 1.33, 95% CI:0.35-5.05, P=0.674) were in line with the unmatched analysis. The follow-up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow-up FMR according to the IPTW analysis (92.2% vs. 98.3%, P=0.033). The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR.

A Comprehensive Review of C. capsularis and C. olitorius: A Source of Nutrition, Essential Phytoconstituents and Pharmacological Activities.

Plant bioactive compounds have gained global significance in terms of both medicinal and economic ramifications due to being easily accessible and are believed to be effective with fewer side effects. Growing relevant clinical and scientific evidence has become an important criterion for accepting traditional health claims of medicinal plants and also supports the traditional uses of Corchorus as folk medicine. C. capsularis and C. olitorius have broad applications ranging from textile to biocomposite, and young leaves and shoots are used as healthy vegetables and have long been used as traditional remedies for fever, ascites, algesia, liver disorders, piles, and tumors in many cultures. This review systematically summarized and emphasized the nutritional attributes, mostly available bioactive compounds, and biological and potential pharmaceutical properties of C. capsularis and C. olitorius, disclosed to users and non-users. Results suggest that various phytochemicals such as cardiac glycosides, phenols, flavonoids, sterols, lipids, and fatty acids were found or analytically identified in different plant parts (leaf, stem, seed, and root), and many of them are responsible for pharmacological properties and their antitumor, anticancer, antioxidant, antinociceptive, anti-inflammatory, analgesic, antipyretic, antiviral, antibacterial, anticonvulsant, antidiabetic and antiobesity, and cardiovascular properties help to prevent and cure many chronic diseases. In addition to their use in traditional food and medicine, their leaves have also been developed for skin care products, and some other possible uses are described. From this review, it is clear that the isolated compounds of both species have great potential to prevent and treat various diseases and be used as functional foods. In conclusion, this comprehensive review establishes a significant reference base for future research into various medical and functional food applications.

Optimal Technique for Introducing Schwann Cells Into Peripheral Nerve Repair Sites.

Peripheral nerve injury (PNI) is found in a relatively large portion of trauma patients. If the injury is severe, such as with the presence of a long segmental gap, PNI can present a challenge for treatment. The current clinical standard of nerve harvest for the repair of long segmental gap PNI can lead to many potential complications. While other methods have been utilized, recent evidence indicates the relevance of cell therapies, particularly through the use of Schwann cells, for the treatment of PNI. Schwann cells (SCs) are integral in the regeneration and restoration of function following PNI. SCs are able to dedifferentiate and proliferate, remove myelin and axonal debris, and are supportive in axonal regeneration. Our laboratory has demonstrated that SCs are effective in the treatment of severe PNI when axon guidance channels are utilized. However, in order for this treatment to be effective, optimal techniques for cellular placement must be used. Thus, here we provide relevant background information, preclinical, and clinical evidence for our method in the treatment of severe PNI through the use of SCs and axon guidance channels.

P-233 Deep ensembles-based AI as a tool to support embryo grading and clinical pregnancy prediction

Abstract Study question Can deep learning accurately evaluate embryo grades and predict clinical pregnancy while providing relevant clinical evidence, not just results from a black box? Summary answer The sophisticated ensemble method can improve the predictive performance for embryo grades and clinical pregnancy, while providing clinically relevant evidence. What is known already Previous studies have shown that AI can predict the IVF outcomes by analyzing the images of embryos. In many literature, AI outperformed human because AI could identify features human eyes could not easily detect. However, clinicians have been cautious to adopt the AI technology due to the black box nature of AI algorithms. In this study, we increased the predictive power of AI as well as providing evidence of the prediction by using deep ensembles and Grad-CAM images. Study design, size, duration We performed a retrospective study of single static images of 727 Day 5 blastocysts from 270 patients who underwent single embryo transfer at a single in vitro fertilization (IVF) clinic between January 2015 and March 2021. The images were collected from standard optical light microscopes and matched with metadata such as embryo grades and pregnancy outcomes. Participants/materials, setting, methods Two different models were designed: an automatic embryo grading model and a pregnancy prediction model. Embryologists labeled a day 5 embryo “GEM,” a good embryo if 4AA/AB or above in the Gardner system and pregnancy was defined as the presence of a fetal heartbeat (FHB). Deep ensembles were applied by training four convolutional neural networks (CNNs) and Grad-CAM images were extracted from the last layer and reviewed by experts. Main results and the role of chance Under several single CNNs, the highest AUROCs of the embryo grading model and the pregnancy prediction model were 0.80 and 0.67, respectively. After applying deep ensembles, the AUROCs of the two models increased to 0.84 and 0.72, respectively. When the F1-score for the positive cases were maximized by adjusting the threshold of ensembles, accuracy, sensitivity and specificity of the embryo grading model were 88.1%, 92.9% and 62.5% respectively. For the pregnancy prediction model, accuracy, sensitivity and specificity were 66.3%, 77.1% and 55.6% respectively. The accuracy of GEM predicting pregnancy for the embryologists and the embryo grading AI model was 47.3% and 59.2%, respectively. It is noteworthy that the AI pregnancy prediction model outperformed the embryologists while successfully auto-grading embryos, a strong evidence that AI considered more features for prediction than what was used for grading. It was also noted from the review of the Grad-CAM images that the both AI models were focusing on the ICM, TE and hatching. Although their area of focus was the same, the pregnancy prediction model was able to make better predictions than the embryologists and the embryo grading model. Limitations, reasons for caution This study has limitations as it is a retrospective study performed on embryo images from a single IVF center. In addition, including other variables such as clinical data may enhance the models. Wider implications of the findings We showed that deep learning can automatically grade embryos and more accurately predict pregnancy than embryologists. Furthermore, the embryologists confirmed the model was looking at key features like ICM, TE and hatching. Sharing such evidence with clinicians can be a necessary step for AI to be adopted for clinical practice. Trial registration number not applicable

Interactions Between Natural Products and Tamoxifen in Breast Cancer: A Comprehensive Literature Review.

Introduction: Tamoxifen (TAM) is the most commonly used hormone therapeutic drug for the treatment of estrogen receptor-positive (ER+) breast cancer. 30%–70% of clinical breast cancer patients use natural products, which may increase the likelihood of drug interactions. Objective: To evaluate the evidence for the interactions between natural products and TAM in breast cancer. Methods: Electronic databases, including PubMed, CINAHL Plus (via EbscoHost), European PMC, Medline, and Google Scholar, were searched for relevant publications. The search terms include complementary and alternative medicine, natural products, plant products, herbs, interactions, tamoxifen, breast cancer, and their combinations. Results: Various in vitro and in vivo studies demonstrated that the combined use of natural products with TAM produced synergistic anti-cancer effects, including improved inhibition of tumor cell growth and TAM sensitivity and reduced side effects or toxicity of TAM. In contrast, some natural products, including Angelica sinensis (Oliv.) Diels [Apiaceae], Paeonia lactiflora Pall., Rehmannia glutinosa (Gaertn.) DC., Astragalus mongholicus Bunge, and Glycyrrhiza glabra L. [Fabaceae], showed estrogen-like activity, which may reduce the anti-cancer effect of TAM. Some natural products, including morin, silybin, epigallocatechin gallate (EGCG), myricetin, baicalein, curcumin, kaempferol, or quercetin, were found to increase the bioavailability of TAM and its metabolites in vivo. However, three are limited clinical studies on the combination of natural products and TAM. Conclusion: There is evidence for potential interactions of various natural products with TAM in pre-clinical studies, although the relevant clinical evidence is still lacking. Further studies are warranted to evaluate the potential interactions of natural products with TAM in clinical settings.