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Journal of the American Heart... Jul 2024Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective...
BACKGROUND
Cardiac amyloidosis (CA) is frequently found in older patients with aortic stenosis (AS). However, the prevalence of AS among patients with CA is unknown. The objective was to study the prevalence and prognostic impact of AS among patients with CA.
METHODS AND RESULTS
We conducted a retrospective analysis of a prospective registry comprising 976 patients with native aortic valves who were confirmed with wild type transthyretin amyloid (ATTRwt), hereditary variant transthyretin amyloid (ATTRv), or immunoglobulin light-chain (AL) CA. CA patients' echocardiograms were re-analyzed focusing on the aortic valve. Multivariable Cox regression analysis was performed to assess the mortality risk associated with moderate or greater AS in ATTRwt CA. The crude prevalence of AS among patients with CA was 26% in ATTRwt, 8% in ATTRv, and 5% in AL. Compared with population-based controls, all types of CA had higher age- and sex-standardized rate ratios (SRRs) of having any degree of AS (AL: SRR, 2.62; 95% Confidence Interval (CI) [1.09-3.64]; ATTRv: SRR, 3.41; 95%CI [1.64-4.60]; ATTRwt: SRR, 10.8; 95%CI [5.25-14.53]). Compared with hospital controls, only ATTRwt had a higher SRR of having any degree of AS (AL: SRR, 0.97, 95%CI [0.56-1.14]; ATTRv: SRR, 1.27; 95%CI [0.85-1.44]; ATTRwt: SRR, 4.01; 95%CI [2.71-4.54]). Among patients with ATTRwt, moderate or greater AS was not associated with increased all-cause death after multivariable adjustment (hazard ratio, 0.71; 95%CI [0.42-1.19]; =0.19).
CONCLUSIONS
Among patients with CA, ATTRwt but not ATTRv or AL is associated with a higher prevalence of patients with AS compared with hospital controls without CA, even after adjusting for age and sex. In our population, having moderate or greater AS was not associated with a worse outcome in patients with ATTRwt.
Topics: Humans; Male; Female; Prevalence; Aged; Retrospective Studies; Aortic Valve Stenosis; Prognosis; Cardiomyopathies; Aged, 80 and over; Registries; Amyloid Neuropathies, Familial; Risk Factors; Echocardiography; Middle Aged; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Prealbumin; Aortic Valve
PubMed: 38904242
DOI: 10.1161/JAHA.124.034723 -
Frontiers in Oncology 2024Chemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb...
BACKGROUND
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a dose-limiting side effect observed in breast cancer patients. Its primary clinical manifestations include limb numbness, tingling sensations, hypoesthesia, or paresthesia. In severe instances, some patients may also encounter muscle cramps, weakness, and pain, leading to potential paralysis. The onset of CIPN significantly impacts the quality of life for cancer patients. Hence, it is imperative to explore preventive strategies for managing CIPN.
METHODS
We searched for relevant randomized controlled trials (RCTs) and non-randomized controlled trials (non-RCTs) in several databases. The primary outcome measures encompassed the Patient Neurotoxicity Questionnaire (PNQ), the Functional Assessment of Cancer Therapy-Taxane (FACT-Taxane), and the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Secondary outcomes aimed to evaluate the quality of life and the tolerability of ice gloves. Meta-analysis was conducted using RevMan 5.3 software to determine the relative risk ratio (RR) and 95% confidence interval (CI).
RESULTS
We conducted an analysis involving 372 patients across seven trials. In our meta-analysis, the use of ice gloves demonstrated non-significant results in reducing the incidence of both motor and sensory neuropathy, as assessed through CTCAE (sensory: RR: 0.94; 95% CI: 0.85 to 1.02; P = 0.15; motor: RR: 1.04; 95% CI: 0.88 to 1.22; P = 0.64). Similarly, when evaluated using the PNQ, there was no significant reduction observed in the incidence of sensory and motor neuropathy (sensory: RR: 0.49; 95% CI: 0.20 to 1.20; P = 0.12; motor: RR: 0.71; 95% CI: 0.26 to 1.99; P = 0.52). Consistently, our conclusions remained unchanged when employing the FACT-Taxane assessment. Regarding the evaluation of the quality of life, our observations suggested a potential improvement with the use of ice gloves, and participants exhibited moderate tolerance towards them.
CONCLUSION
Ice gloves are a reasonable option for the treatment of CIPN in patients undergoing chemotherapy for breast cancer. However, the effectiveness of ice gloves in combating CIPN remains inconclusive at this time due to the low quality and limited number of clinical trials on this topic.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023457045, identifier CRD42023457045.
PubMed: 38903710
DOI: 10.3389/fonc.2024.1366782 -
BMC Musculoskeletal Disorders Jun 2024Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational... (Observational Study)
Observational Study
BACKGROUND
Low back pain, a common problem worldwide, causes more global disability than any other condition and is associated with high costs to society. This observational registry-based study describes the current trends in the medical treatment of neuropathic low back pain in the Swedish region of Västra Götaland, which has a population of 1.7 million. The study aims to; (1) identify the prevalence of neuropathic low back pain within the study population; (2) to explore the patterns of medical treatment utilization, including the prevalence and distribution of opioids (OG) and analgesics specified for neuropathic low back pain (NG) and (3) to evaluate the long-term trends and changes in medical treatment practice for neuropathic low back pain over the study period.
METHODS
This study includes a descriptive analysis of aggregated data extracted from the Swedish primary care registry VEGA and the pharmaceutical prescription registry Digitalis between the years 2017 and 2021. The data were stratified by year, age, gender, pharmaceutical code (ATC), and sub-diagnoses and presented as the prevalence of unique patients retrieving prescribed medication within six months before or after a registered diagnosis of neuropathic low back pain. The pharmaceutical codes were furthermore grouped into two groups depending on their mechanism of action; opioid group (OG) and neuropathic group (NG).
RESULTS
In all four diagnosis groups, more patients used opioid analgesics than neuropathic analgesics. The greatest difference between the opioid group and neuropathic group was in the lumbar spinal stenosis diagnosis group (67.1% vs. 40.6%), followed by the lumbar root canal stenosis diagnosis (65.9% vs. 44.2%), the nerve root and plexus compressions in intervertebral disc disorders diagnosis (57.5% vs. 40.8%), and lumbago with sciatica diagnosis (38.4% vs. 22.7%).
CONCLUSIONS
The trends suggest a general increase in the prescription rate and therefore patients' use of neuropathic analgesics for neuropathic pain associated with the studied diagnoses. However, opioid treatment remains the most common. The results indicate that the treatment for neuropathic low back pain needs to be improved.
Topics: Humans; Sweden; Registries; Low Back Pain; Male; Female; Middle Aged; Neuralgia; Adult; Aged; Analgesics, Opioid; Analgesics; Prevalence; Young Adult; Adolescent; Aged, 80 and over; Practice Patterns, Physicians'
PubMed: 38902709
DOI: 10.1186/s12891-024-07599-4 -
PloS One 2024Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In...
Neurofibromatosis Type I (NF1) is a rare genetic disorder. NF1 patients frequently develop a benign tumor in peripheral nerve plexuses called plexiform neurofibroma. In the past two decades, tissue-specific Nf1 knockout mouse models were developed using commercially available tissue-specific Cre recombinase and the Nf1 flox mice to mimic neurofibroma development. However, these models develop para-spinal neurofibroma, recapitulating a rare type of neurofibroma found in NF1 patients. The NPcis mouse model developed a malignant version of neurofibroma called malignant peripheral nerve sheath tumor (MPNST) within 3 to 6 months but intriguingly without apparent benign precursor lesion. Here, we revisited the NPcis model and discovered that about 20% display clinical signs similar to Nf1 tissue-specific knockout mice models. However, a systematic histological analysis could not explain the clinical signs we observed although we noticed lesions reminiscent of a neurofibroma in a peripheral nerve, a cutaneous neurofibroma, and para-spinal neurofibroma on rare occasions in NPcis mice. We also observed that 10% of the mice developed a malignant peripheral nerve sheath tumor (MPNST) spontaneously, coinciding with their earring tag identification. Strikingly, half of the sciatic nerves from NPcis mice developed plexiform neurofibroma within 1-6 months when intentionally injured. Thus, we provided a procedure to turn the widely used NPcis sarcoma model into a model recapitulating plexiform neurofibroma.
Topics: Animals; Neurofibroma, Plexiform; Disease Models, Animal; Mice; Sciatic Nerve; Mice, Knockout; Neurofibromatosis 1; Neurofibromin 1
PubMed: 38900740
DOI: 10.1371/journal.pone.0301040 -
ELife Jun 2024Autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) are only partially represented in current experimental models and the development...
Spontaneous human CD8 T cell and autoimmune encephalomyelitis-induced CD4/CD8 T cell lesions in the brain and spinal cord of HLA-DRB1*15-positive multiple sclerosis humanized immune system mice.
Autoimmune diseases of the central nervous system (CNS) such as multiple sclerosis (MS) are only partially represented in current experimental models and the development of humanized immune mice is crucial for better understanding of immunopathogenesis and testing of therapeutics. We describe a humanized mouse model with several key features of MS. Severely immunodeficient B2m-NOG mice were transplanted with peripheral blood mononuclear cells (PBMCs) from HLA-DRB1-typed MS and healthy (HI) donors and showed rapid engraftment by human T and B lymphocytes. Mice receiving cells from MS patients with recent/ongoing Epstein-Barr virus reactivation showed high B cell engraftment capacity. Both HLA-DRB1*15 (DR15) MS and DR15 HI mice, not HLA-DRB1*13 MS mice, developed human T cell infiltration of CNS borders and parenchyma. DR15 MS mice uniquely developed inflammatory lesions in brain and spinal cord gray matter, with spontaneous, hCD8 T cell lesions, and mixed hCD8/hCD4 T cell lesions in EAE immunized mice, with variation in localization and severity between different patient donors. Main limitations of this model for further development are poor monocyte engraftment and lack of demyelination, lymph node organization, and IgG responses. These results show that PBMC humanized mice represent promising research tools for investigating MS immunopathology in a patient-specific approach.
Topics: Animals; Humans; Multiple Sclerosis; Mice; HLA-DRB1 Chains; CD8-Positive T-Lymphocytes; Spinal Cord; Disease Models, Animal; Brain; Encephalomyelitis, Autoimmune, Experimental; CD4-Positive T-Lymphocytes; Female
PubMed: 38900149
DOI: 10.7554/eLife.88826 -
Cureus May 2024Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and...
Introduction Nonalcoholic fatty liver disease (NAFLD) presents as a multisystem disorder, heightening the risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs). Occupation emerges as a significant factor influencing the occurrence of NAFLD. Research indicates that individuals engaged in shift work face an elevated risk of NAFLD, alongside obesity and T2DM, attributed to disruptions in their circadian rhythm, which precipitate hepatic steatosis and inflammation. Remarkably, peripheral neuropathy has been observed in conjunction with advanced liver disorders and NAFLD in the general population. However, the correlation between NAFLD and peripheral neuropathy remains unestablished in shift workers. Objective To identify NAFLD in seemingly healthy rotating shift workers and assess any potential impact of NAFLD on nerve function in this demographic. Methods This cross-sectional study involved 73 apparently healthy nonalcoholic security guards (aged 35 to 60 years) working in rotating shifts. The study included a comprehensive assessment, beginning with a medical history, an evaluation of physical activity, and anthropometric measurements. Confirmation of NAFLD was achieved through abdominal ultrasonography (USG), followed by the analysis of biochemical parameters. Motor and sensory nerve conduction studies (NCS) were conducted on participants with normal vitamin B12 levels using the Aleron electromyograph (EMG) machine (Recorders and Medicare Systems Private Ltd, Budanpur, India). The evaluation encompassed the Median and Common Peroneal motor nerves, as well as Median and Sural sensory nerves. Recorded parameters for motor nerves included distal motor latency (DML), compound muscle action potential (CMAP) amplitude, conduction velocity (CV), and F-wave minimum latency (F-wave), while sensory nerve parameters comprised sensory onset latency (SOL), sensory nerve action potential (SNAP) amplitude, and CV. Results Among 73 healthy security guards working in rotating shifts, 76.1% were diagnosed with NAFLD through abdominal ultrasound. Following participant withdrawals and exclusions due to vitamin B12 deficiency, a comparison of NCS parameters between NAFLD (n=24) and Non-NAFLD (n=12) groups revealed no significant disparities in motor or sensory parameters, except for a slightly diminished CMAP amplitude in the peroneal nerve of NAFLD subjects (8.21±2.83mV vs ±10.22±2.30 mV, p< 0.040). However, these differences fell within normal ranges, indicating no notable impact on peripheral nerve conduction in the presence of NAFLD. Conclusion The results indicate a high prevalence of NAFLD among individuals working rotating shifts. Moreover, the investigation suggests that despite the presence of NAFLD, there is no discernible influence on motor and sensory peripheral nerve conduction, particularly in common peroneal, median, and sural nerves.
PubMed: 38899241
DOI: 10.7759/cureus.60632 -
Journal of Diabetes Research 2024Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are... (Review)
Review
Review and Evaluation of European National Clinical Practice Guidelines for the Treatment and Management of Active Charcot Neuro-Osteoarthropathy in Diabetes Using the AGREE-II Tool Identifies an Absence of Evidence-Based Recommendations.
Charcot neuro-osteoarthropathy (CNO) is a rare but devastating complication of diabetes associated with high rates of morbidity; yet, many nonfoot specialists are unaware of it, resulting in missed and delayed diagnosis. Clinical practice guidelines (CPGs) have proven useful in improving quality of care and standardizing practice in diabetes and diabetic foot care. However, little is known about the consistency in recommendations for identification and management of active CNO. The aim of this study is to review European national diabetes CPGs for the diagnosis and management of active CNO and to assess their methodological rigor and transparency. A systematic search was performed to identify diabetes national CPGs across Europe. Guidelines in any language were reviewed to explore whether they provided a definition for active CNO and recommendations for diagnosis, monitoring, and management. Methodological rigor and transparency were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE-II) tool, which comprises 23 key items organized within six domains with an overall guideline assessment score of ≥ 60% considered to be of adequate quality to recommend use. Each guideline was assessed by two reviewers, and inter-rater agreement (Kendall's ) was calculated for AGREE-II scores. Seventeen CPGs met the inclusion criteria. Breadth of CNO content varied across guidelines (median (IQR) word count: 327; Q1 = 151; Q3 = 790), and 53% provided a definition for active CNO. Recommendations for diagnosis and monitoring were provided by 82% and 53%, respectively, with offloading being the most common management recommendation (88%). Four guidelines (24%) reached threshold for recommendation for use in clinical practice (≥ 60%) with the scope and purpose domain scoring highest (mean (SD): 67%, ± 23%). The remaining domains had average scores ranging between 19% and 53%. Inter-rater agreement was strong ( = 0.882; < 0.001). European national CPGs for diabetes provide limited recommendations on active CNO. All guidelines showcased deficits in their methodology, suggesting that more rigorous methods should be employed for diabetes CPG development across Europe.
Topics: Humans; Europe; Practice Guidelines as Topic; Arthropathy, Neurogenic; Evidence-Based Medicine; Diabetic Foot; Diabetic Neuropathies
PubMed: 38899148
DOI: 10.1155/2024/7533891 -
Translational Neurodegeneration Jun 2024The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could... (Review)
Review
The central nervous system (CNS) is integrated by glial and neuronal cells, and both release extracellular vesicles (EVs) that participate in CNS homeostasis. EVs could be one of the best candidates to operate as nanosized biological platforms for analysing multidimensional bioactive cargos, which are protected during systemic circulation of EVs. Having a window into the molecular level processes that are happening in the CNS could open a new avenue in CNS research. This raises a particular point of interest: can CNS-derived EVs in blood serve as circulating biomarkers that reflect the pathological status of neurological diseases? L1 cell adhesion molecule (L1CAM) is a widely reported biomarker to identify CNS-derived EVs in peripheral blood. However, it has been demonstrated that L1CAM is also expressed outside the CNS. Given that principal data related to neurodegenerative diseases, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease were obtained using L1CAM-positive EVs, efforts to overcome present challenges related to its specificity are required. In this sense, other surface biomarkers for CNS-derived EVs, such as glutamate aspartate transporter (GLAST) and myelin oligodendrocyte glycoprotein (MOG), among others, have started to be used. Establishing a panel of EV biomarkers to analyse CNS-derived EVs in blood could increase the specificity and sensitivity necessary for these types of studies. This review covers the main evidence related to CNS-derived EVs in cerebrospinal fluid and blood samples of patients with neurological diseases, focusing on the reported biomarkers and the technical possibilities for their isolation. EVs are emerging as a mirror of brain physiopathology, reflecting both localized and systemic changes. Therefore, when the technical hindrances for EV research and clinical applications are overcome, novel disease-specific panels of EV biomarkers would be discovered to facilitate transformation from traditional medicine to personalized medicine.
Topics: Humans; Extracellular Vesicles; Biomarkers; Central Nervous System; Neurodegenerative Diseases; Animals
PubMed: 38898538
DOI: 10.1186/s40035-024-00418-9 -
Seminars in Oncology Nursing Jun 2024Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not...
OBJECTIVES
Duloxetine, the only American Society of Clinical Oncology (ASCO) treatment recommended for chemotherapy-induced peripheral neuropathy (CIPN) in cancer survivors, is not effective for 40% of survivors. This study examined the ability of a duloxetine-prazosin combination to prevent the development of allodynia and hyperalgesia in a rat model of oxaliplatin-induced peripheral neuropathy (OPIN).
METHODS
Female (n = 24) and male (n = 41) rats were started on duloxetine (15 mg), prazosin (2 mg), or a duloxetine-prazosin combination one week prior to administration of the chemotherapy drug, oxaliplatin, and continued the duloxetine-prazosin combination for 32 days. Behavioral testing for mechanical allodynia and mechanical hyperalgesia was done with selected von Frey filaments over the course of the study.
RESULTS
Overall percent paw withdrawal for rats that received the duloxetine-prazosin combination was significantly lower in female (p < .001 for both conditions) and male (p = .029 for allodynia; p < .001 for hyperalgesia) than those that received water. No significant posttreatment differences were found for allodynia or hyperalgesia between rats treated with duloxetine and rats that received the duloxetine-prazosin combination in either sex.
CONCLUSIONS
These finding provide preliminary evidence that a duloxetine-prazosin combination can prevent the posttreatment development of allodynia and hyperalgesia in both male and female rats; however, the results suggest that the duloxetine-prazosin combination is no more efficacious than duloxetine alone in preventing chronic OIPN.
IMPLICATIONS FOR NURSING PRACTICE
The profession of nursing is built on clinical practice supported by scientific research. The current study addressed the clinical practice problem of prevention and management of painful OIPN, which is a priority area in oncology nursing.
PubMed: 38897856
DOI: 10.1016/j.soncn.2024.151686 -
Health Expectations : An International... Jun 2024Surgery can help patients with leg pain caused by sciatica recover faster, but by 12 months outcomes are similar to nonsurgical management. For many the decision to have...
BACKGROUND
Surgery can help patients with leg pain caused by sciatica recover faster, but by 12 months outcomes are similar to nonsurgical management. For many the decision to have surgery may require reflection, and patient decision aids are an evidence-based clinical tool that can help guide patients through this decision.
OBJECTIVE
The aim of this study was to develop and refine a decision aid for patients with sciatica who are deciding whether to have surgery or 'wait and see' (i.e., try nonsurgical management first).
DESIGN
Semistructured interviews with think-aloud user-testing protocol.
PARTICIPANTS
Twenty clinicians and 20 patients with lived experience of low back pain or sciatica.
OUTCOME MEASURES
Items from Technology Acceptance Model, Preparation for Decision Making Scale and Decision Quality Instrument for Herniated Disc 2.0 (knowledge instrument).
METHODS
The prototype integrated relevant research with working group perspectives, decision aid standards and health literacy guidelines. The research team refined the prototype through seven rounds of user-testing, which involved discussing user-testing feedback and implementing changes before progressing to the next round.
RESULTS
As a result of working group feedback, the decision aid was divided into sections: before, during and after a visit to the surgeon. Across all rounds of user-testing, clinicians rated the resource 5.9/7 (SD = 1.0) for perceived usefulness, and 6.0/7 for perceived ease of use (SD = 0.8). Patients reported the decision aid was easy to understand, on average correctly answering 3.4/5 knowledge questions (SD = 1.2) about surgery for sciatica. The grade reading score for the website was 9.0. Patients scored highly on preparation for decision-making (4.4/5, SD = 0.7), suggesting strong potential to empower patients. Interview feedback showed that patients and clinicians felt the decision aid would encourage question-asking and help patients reflect on personal values.
CONCLUSIONS
Clinicians found the decision aid acceptable, patients found it was easy to understand and both groups felt it would empower patients to actively engage in their care and come to an informed decision that aligned with personal values. Input from the working group and user-testing was crucial for ensuring that the decision aid met patient and clinician needs.
PATIENT OR PUBLIC CONTRIBUTION
Patients and clinicians contributed to prototype development via the working group.
Topics: Humans; Sciatica; Decision Support Techniques; Female; Male; Adult; Middle Aged; Interviews as Topic; Decision Making; Patient Participation
PubMed: 38896009
DOI: 10.1111/hex.14111