Pathophysiological Mechanisms Research Articles

P43 Unmasking posterior reversible encephalopathy syndrome: a hidden threat in juvenile lupus

Abstract Introduction Posterior reversible encephalopathy syndrome (PRES) is a neurological condition identifiable through clinical presentation and magnetic resonance imaging (MRI). While PRES has been rarely documented in children as a complication of juvenile lupus, it remains a potentially reversible condition. However, it can be complicated by vasculopathy, infarction, or haemorrhage. The pathogenesis of PRES is still unclear. In juvenile lupus, the risk factors for PRES are multifaceted and interact with each other, including vasculitis, lupus nephritis, chronic kidney disease (CKD) leading to renal-origin hypertension, and iatrogenic hypertension caused by several hypertension-inducing drugs commonly used as first-line treatments for lupus. Case description A 14-year-old girl diagnosed with lupus presented with persistent fatigue, lower limb oedema, and abdominal symptoms (vomiting and diarrhoea). She experienced two episodes of PRES, three months apart. Active SLE was confirmed through clinical and laboratory findings, including positive autoimmune and serologic results for ENA antibody screen, high levels of anti-double-stranded DNA (>400), and low complements C3 (0.15 g/L) and C4 (<0.03 g/L). Urine analysis revealed 2+ RBCs, 3+ proteins, and an estimated glomerular filtration rate (eGFR) of ∼21 ml/min/1.73 m² with a plasma creatinine of 226 micromol/L. Renal biopsy identified lupus nephritis class IV and chronic kidney disease (CKD) changes, leading to a diagnosis of CKD stage 4. Initial treatment included a course of pulse methylprednisolone (1 g daily for 3 days) alongside rituximab and MMF for remission induction followed by high-dose oral prednisone (2 mg/kg/d). Her blood pressure started to increase following the first methylprednisolone pulse. In addition, two weeks later, severe fluid overload necessitated dialysis. Despite dialysis and the use of four antihypertensive agents (lisinopril, amlodipine, atenolol, doxazosin), her blood pressure fluctuated and remained uncontrolled. A week later, she experienced focal seizures. While a CT brain scan showed no abnormalities, an MRI revealed multifocal areas of bilateral cerebral hemispheric cortico-subcortical signal and diffusion alteration, indicating evolving PRES. A steroid weaning plan was implemented, and IV cyclophosphamide was initiated according to the National Institutes of Health protocol. Eight weeks later, she had another PRES episode, presenting with seizures confirmed by MRI findings. On both occasions, hypertensive encephalopathy was promptly recognized, and she was transferred to the PICU. Fortunately, her symptoms completely resolved within 12 hours of anticonvulsant and antihypertensive therapies. Discussion Common triggers of PRES include autoimmune conditions such as systemic lupus erythematosus (SLE), hypertensive encephalopathy, and drug toxicities (mainly cytotoxic and immunosuppressive drugs), all of which interact in lupus patients. However, it remains unclear how each factor contributes to the development of PRES. Additionally, the exact pathophysiological mechanism behind PRES is still debated. The two most widely accepted hypotheses involve: firstly, increased arterial blood pressure overwhelming cerebral autoregulatory mechanisms, leading to vascular leakage and vasogenic oedema. Secondly, endothelial dysfunction, where endothelial damage caused by circulating toxins enhances the release of vasoactive and immunogenic agents, altering vascular permeability. Our patient’s development of PRES is multifactorial, with lupus nephritis being a primary cause, aggravated by chronic kidney disease, leading to salt and water retention, which was further exacerbated by prednisolone. Other drugs, such as rituximab and cyclophosphamide, might have also been implicated in causing hypertension. PRES following rituximab infusion has been documented, with onset ranging from immediately after infusion to up to four weeks later. Proposed mechanisms include compromised blood-brain barrier integrity and immune dysregulation. Intravenous cyclophosphamide has also been identified as a potential trigger for PRES in patients with and without SLE, though the exact reason for this remains unclear. The dual role of these drugs in potentially precipitating life-threatening risks like PRES while being therapeutic agents presents a confusing dilemma. Much remains to be learned to enable the prevention and prompt response to PRES. Key learning points • Juvenile lupus with PRES is an uncommon neurological manifestation influenced by multiple factors. • Risk factors for PRES in juvenile lupus include lupus nephritis, CKD secondary to lupus, and iatrogenic hypertension including steroids, rituximab, and cyclophosphamide. These factors commonly exist and interplay together. • The pathogenesis of PRES in lupus, including the role of drugs, remains unclear. • Patients with lupus should be closely monitored, particularly their blood pressure. • Early diagnosis and prompt treatment of PRES can reverse radiologic and neurologic findings, leading to a favourable prognosis.

New insights on the link between Epstein‑Barr virus infection and cognitive decline in neurodegenerative diseases (Review).

Cognitive decline is a frequent complaint in healthy controls and neurological patients, regardless of the underlying pathology. Whilst cognitive impairment can be easily diagnosed in the more advanced stages of neurodegenerative diseases, early detection can be challenging. This is mainly the consequence of the incomplete understanding of the underlying pathophysiological mechanisms. In addition, currently available neurological treatments do not specifically target cognitive decline, since other motor and non-motor symptoms, such as bradykinesia, tremor, autonomic disturbances and depression, are of greater relevance from a therapeutic perspective. In this context, prospective studies must address a number of issues, including the risk factors associated with cognitive deficits in neurodegenerative diseases. The present review aims to offer a novel perspective on the association between Epstein-Barr virus infection and cognitive decline found in patients with neurodegenerative disorders. Specifically, relevant epidemiological studies and clinical trials explaining this connection were reviewed, focusing on the most frequent neurodegenerative disorders. They are namely Alzheimer's disease, Parkinson's disease and multiple sclerosis. Despite their limitations, possible underlying pathophysiological mechanisms that explain the impact of Epstein-Barr virus infection on cognitive decline are expected to offer novel study directions on this clinically relevant topic.

Nutritional deficiency in patients with liver cirrhosis

Liver cirrhosis is a prevalent cause of death, particularly in developing countries. The global mortality rate is 15–30 cases per 100 thousand population (more than 2.4% of the total mortality). Among the most severe complications of liver cirrhosis, nutritional deficiency increases not only the duration of hospital stay, but also mortality. This implies that malnutrition is not only a relevant clinical characteristic of liver cirrhosis, but it should also be considered as a significant complication requiring timely and appropriate therapy to enhance prognosis. This review emphasizes contemporary concepts regarding nutritional deficiency in liver cirrhosis patients and the significance of early diagnosis of this condition. Additional research is required to comprehensively understand the pathophysiological mechanisms of malnutrition in liver cirrhosis patients. It is anticipated that the results will assist in the optimization of diagnostic screening and the identification of a “therapeutic target,” considering factors influencing the development and progression of nutritional deficiency, thereby reducing the incidence of infectious complications and lowering the mortality rate among liver cirrhosis patients.

Delirium and frailty in older adults: Clinical overlap and biological underpinnings.

Frailty and delirium are two common geriatric syndromes sharing several clinical characteristics, risk factors, and negative outcomes. Understanding their interdependency is crucial to identify shared mechanisms and implement initiatives to reduce the associated burden. This literature review summarizes scientific evidence on the complex interplay between frailty and delirium; clinical, epidemiological, and pathophysiological commonalities; and current knowledge gaps. We conducted a PubMed systematic search in June 2023, which yielded 118 eligible articles out of 991. The synthesis of the results-carried out by content experts-highlights overlapping risk factors, clinical phenotypes, and outcomes and explores the influence of one syndrome on the onset of the other. Common pathophysiological mechanisms identified include inflammation, neurodegeneration, metabolic insufficiency, and vascular burden. The review suggests that frailty is a risk factor for delirium, with some support for delirium associated with accelerated frailty. The proposed unifying framework supports the integration and measurement of both constructs in research and clinical practice, identifying the geroscience approach as a potential avenue to develop strategies for both conditions. In conclusion, we suggest that frailty and delirium might be alternative-sometimes coexisting-manifestations of accelerated biological aging. Clinically, the concepts addressed in this review can help approach older adults with either frailty or delirium from a different perspective. From a research standpoint, longitudinal studies are needed to explore the hypothesis that specific pathways within the biology of aging may underlie the clinical manifestations of frailty and delirium. Such research will pave the way for future understanding of other geriatric syndromes as well.

Unraveling autonomic cardiovascular control complexity during orthostatic stress: Insights from a mathematical model

Understanding cardiovascular control mediated by the autonomic system remains challenging due to its inherent complexity. Consequently, syndromes such as orthostatic intolerance continue to evoke debates regarding the underlying pathophysiological mechanisms. This study develops a comprehensive mathematical model simulating the control of the sympathetic branch of the cardiovascular system in individuals with normal and abnormal responses to the head-up-tilt test. We recruited four young women: one control, one with vasovagal syncope, one with orthostatic hypertension, and one with orthostatic hypotension, exposing them to an orthostatic head-up tilt test (HUTT) employing non-invasive methods to measure electrocardiography and continuous blood pressure.Our work encompasses a compartmental model formulated using a system of ordinary differential equations. Using heart rate as input, we predict blood pressure, flow, and volume in compartments representing the veins, arteries, heart, and the sympathetic branch of the baroreflex control system. The latter is modulated by high- and low-pressure baroreceptor afferents activated by changes in blood pressure induced by the HUTT. Sensitivity analysis, parameter subset selection, and optimization are employed to estimate patient-specific parameters associated with autonomic performance. The model has seven sensitive and identifiable parameters with significant physiological relevance that can serve as biomarkers for patient classification.Results show that the model can reproduce a spectrum of blood pressure responses successfully, fitting the trajectory displayed by the experimental data. The controller exhibits behavior that emulates the operation of the sympathetic system. These encouraging findings underscore the potential of computational methods in evaluating pathologies associated with autonomic nervous system control, warranting further exploration and novel approaches.

Coagulopathy and acute pancreatitis: pathophysiology and clinical treatment

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients’ prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

Prolonged Visual Evoked Potential Latencies in Dogs Naturally Infected with Canine Distemper Virus

Canine distemper (CD) is a deadly, multi-system infection caused by a Morbillivirus. The canine distemper virus (CDV) frequently affects the nervous system with demyelinating leukoencephalitis, the most common neurological lesion. The disease has been linked to multiple sclerosis (MS) in humans due to similar clinical presentation and pathophysiological mechanisms. In MS, visual evoked potentials (VEPs) have been identified as a reliable marker for disease progression, enabling the early detection of clinically suspected lesions. The aim of this study was to determine if there are any abnormalities in VEP responses in dogs with neurological CD. Visual evoked potentials and electroretinogram (ERG) were recorded at both the cranial and spinal levels in dogs naturally infected with CDV and in healthy dogs. The results in the CDV-infected group revealed a bilateral increase in the latency of N1, P1, N2, P2, and N3 waves of the VEPs, without any alterations in their amplitudes. No significant differences were observed in the ERG between the groups. These results suggest that altered VEP responses could serve as an early diagnostic indicator of neurological damage caused by distemper. Therefore, conducting these studies could potentially aid in the detection of central nervous conduction disorders during the subclinical phases of the disease.

RELATIONSHIP BETWEEN MYOCARDITIS AND DENGUE

Introduction: Myocarditis, an inflammation of the heart muscle, can arise as a complication of dengue fever, a mosquito-borne disease. It is essential to adopt a multidisciplinary approach to monitor and treat cardiac complications in patients with dengue fever at an early stage. Diagnostic tests include serology, PCR, and echocardiography. From a review study on cardiac involvement in dengue, it was found that this complication is significant and demands a multidisciplinary approach . Objective: The objective of this study was to conduct a comprehensive integrative review to explore the relationship between myocarditis and dengue fever. Methodology: Articles were searched in databases such as PubMed, Google Scholar,Ministry of Health, and ScienceDirect, using search terms in both Portuguese and English. Out of 122 articles found, 74 were selected for analysis, and 13 were included in the results. Results: The studies examined the relationship between dengue fever and myocarditis, with a focus on the cardiovascular manifestations of dengue fever and the prevalence of myocarditis in infected patients. Analysis of the articles revealed a significant prevalence of myocarditis in patients with dengue, highlighting a strong association between the two conditions. Discussion: Dengue patients frequently present with cardiac issues such as myocarditis, necessitating early detection to prevent serious complications. Effective vector control is crucial to reducing the impact of dengue. These findings provide direction for future research and the development of targeted therapies. Conclusion: Early identification of cardiac complications, such as myocarditis in dengue patients, is crucial to reducing morbidity and mortality. Ongoing research into the pathophysiological mechanisms is vital for the development of specific treatments. The study concludes that myocarditis is commonly associated with dengue, requiring meticulous medical monitoring.

Hyperuricemia and epiretinal pathologies: a review of pathophysiological links and clinical implications

Hyperuricemia (HUA), defined by elevated serum uric acid levels, is well-established in its association with systemic conditions like gout and cardiovascular diseases. Recently, however, emerging research has revealed a potential connection between HUA and ocular disorders, particularly epiretinal pathologies. This review investigates the pathophysiological mechanisms linking HUA to epiretinal conditions, including epiretinal membrane formation, macular edema, and retinal vascular diseases. By thoroughly analyzing current literature, this review seeks to deepen the understanding of the relationship between HUA and epiretinal disorders, with the aim of informing new therapeutic strategies and enhancing patient outcomes.

The role of inflammatory response and metabolic reprogramming in sepsis-associated acute kidney injury: mechanistic insights and therapeutic potential

Sepsis represents a severe condition characterized by organ dysfunction resulting from a dysregulated host response to infection. Among the organs affected, the kidneys are particularly vulnerable, with significant functional impairment that markedly elevates mortality rates. Previous researches have highlighted that both inflammatory response dysregulation and metabolic reprogramming are crucial in the onset and progression of sepsis associated acute kidney injury (SA-AKI), making these processes potential targets for innovative therapies. This study aims to elucidate the pathophysiological mechanisms of renal injury in sepsis by perspective of inflammatory response dysregulation, with particular emphasis on pyroptosis, necroptosis, autophagy, and ferroptosis. Furthermore, it will incorporate insights into metabolic reprogramming to provide a detailed analysis of the mechanisms driving SA-AKI and explore potential targeted therapeutic strategies, providing solid theoretical framework for the development of targeted therapies for SA-AKI.

Alterations of regional homogeneity and functional connectivity in different hoehn and yahr stages of Parkinson's disease

PurposeUsing regional homogeneity (ReHo) and functional connectivity (FC) to assess alterations in brain function and their potential relation to different Hoehn and Yahr (H&Y) stages in Parkinson's disease (PD). Materials and methods66 patients with PD and 57 age- and sex-matched healthy control (HC) participants were recruited. All subjects underwent clinical assessments and resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We analyzed alterations in regional brain activity using ReHo analyses in all subjects and further explored their relationship to disease severity. Finally, the brain region significantly associated with disease severity was used as a seed point to analyze the FC changes between it and other brain regions in the whole brain. ResultsCompared with HC participants, PD patients showed a significant decrease ReHo in the sensorimotor network (bilateral precentral and postcentral gyrus). The ReHo value of the left precentral gyrus in PD patients decreased with increasing H&Y stage and correlated negatively with Unified Parkinson’s Disease Rating Scale (UPDRS) III scores. Further, FC analysis of the left precentral gyrus as a region of interest showed that functional activity between the left precentral gyrus and sensorimotor network, default network, and visual network was decreased. ConclusionThe left precentral gyrus plays an important role in the pathophysiological mechanisms of PD patients, and this finding further highlights the potential of the primary motor cortex (M1) as a non-invasive therapeutic target for neuromodulation in PD patients.

Oxidative Stress and Inflammation in Myocardial Ischemia-Reperfusion Injury: Protective Effects of Plant-Derived Natural Active Compounds.

Acute myocardial infarction (AMI) remains a leading cause of death among patients with cardiovascular diseases. Percutaneous coronary intervention (PCI) has been the preferred clinical treatment for AMI due to its safety and efficiency. However, research indicates that the rapid restoration of myocardial oxygen supply following PCI can lead to secondary myocardial injury, termed myocardial ischemia-reperfusion injury (MIRI), posing a grave threat to patient survival. Despite ongoing efforts, the mechanisms underlying MIRI are not yet fully elucidated. Among them, oxidative stress and inflammation stand out as critical pathophysiological mechanisms, playing significant roles in MIRI. Natural compounds have shown strong clinical therapeutic potential due to their high efficacy, availability, and low side effects. Many current studies indicate that natural compounds can mitigate MIRI by reducing oxidative stress and inflammatory responses. Therefore, this paper reviews the mechanisms of oxidative stress and inflammation during MIRI and the role of natural compounds in intervening in these processes, aiming to provide a basis and reference for future research and development of drugs for treating MIRI.

TIPIC syndrome in a patient following sorafenib treatment for acute myeloid leukemia: a rare case report

Transient Perivascular Inflammation of the\ Carotid Artery (TIPIC) syndrome is uncommon, and cases of TIPIC induced by the targeted drug, sorafenib, are extremely rare. This case report describes a patient with acute myeloid leukemia carrying an FMS‐like tyrosine kinase 3 mutation, who developed TIPIC syndrome, which may have been induced by sorafenib treatment. A 65-year-old woman diagnosed with acute myeloid leukemia experienced severe neck pain and sclerotic blisters on her palms and soles during sorafenib treatment. Carotid ultrasound revealed thickening of the right common carotid artery (RCCA) wall, and magnetic resonance imaging revealed perivascular tissue edema in the distal RCCA. Following clinical and imaging assessments, the patient was diagnosed with TIPIC syndrome. Treatment involved a one-week course of oral steroid therapy with dexamethasone and non-steroidal anti-inflammatory drugs, which led to complete clinical recovery. TIPIC syndrome involves transient nonspecific perivascular inflammation of the carotid adventitia; however, the precise underlying cause remains unclear. In this study, we report a rare case and explore the potential pathophysiological mechanisms through a review of the existing literature.

Relationship between autonomic and peripheral neuropathies and cardiovascular outcomes in diabetes

This review explores the complex relationship between diabetic neuropathy and cardiovascular disease (CVD). Neuropathy, a common complication of type 1 and type 2 diabetes, is divided into autonomic and peripheral types, each impacting cardiovascular health. Cardiovascular autonomic neuropathy, a form of autonomic neuropathy, is associated with various CVD complications, including arrhythmias, impaired nocturnal blood pressure regulation, and increased mortality. The prevalence of cardiovascular autonomic neuropathy varies depending on the type and duration of diabetes and is influenced by factors like glycemic control and metabolic stress. Peripheral polyneuropathy, which is often linked to diabetic foot disease, is also correlated with elevated CVD risk; research suggests shared pathophysiological mechanisms between peripheral neuropathy and cardiovascular conditions. Screening for neuropathies using tools like the Michigan Neuropathy Screening Instrument and heart rate variability analyses can facilitate early detection of CVD risk. Additionally, emerging technologies, like deep learning models, have demonstrated promise in detecting early cardiovascular patterns associated with autonomic neuropathy through electrocardiogram analysis. These findings underscore the value of integrating novel diagnostic approaches for early intervention. As CVD represents a leading cause of death among patients with diabetes, this article emphasizes the need for thorough assessment and proactive management of neuropathy to mitigate cardiovascular risk. The review recommends a multidisciplinary approach to diabetes care, including early screening, accurate risk stratification, and targeted therapeutic strategies to prevent or slow the progression of CVD in patients with autonomic and peripheral neuropathies. Further research is warranted to clarify the optimal intervention strategies for reducing CVD risk in these populations.

Gall stones in metabolic syndrome- addressing the risks in obese individuals

Significant research has been dedicated in recent years to elucidating the pathophysiologic mechanisms behind gallstone development, but the epidemiology of gallstone disease has received comparatively little focus. Numerous studies have emphasized the correlation between metabolic syndrome and gallstones. In this study, we found a positive correlation between complicated gall stones and metabolic syndrome. Hence, screening of obese patient or those with PCOS/uncontrolled diabetes, should be introduced in the protocol for facilitate early diagnosis of gall stones.

Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease

The most prevalent chronic neurodegenerative illness in the world is Alzheimer’s disease (AD). It results in mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial and psychological impact on the relatives of the patients. The review discusses various pathophysiological mechanisms contributing to AD, including amyloid beta, tau protein, inflammation, and other factors, while emphasizing the need for effective disease-modifying therapeutics that alter disease progression rather than merely alleviating symptoms. This review mainly covers medications that are now being studied in clinical trials or recently approved by the FDA that fall under the disease-modifying treatment (DMT) category, which alters the progression of the disease by targeting underlying biological mechanisms rather than merely alleviating symptoms. DMTs focus on improving patient outcomes by slowing cognitive decline, enhancing neuroprotection, and supporting neurogenesis. Additionally, the review covers amyloid-targeting therapies, tau-targeting therapies, neuroprotective therapies, and others. This evaluation specifically looked at studies on FDA-approved novel DMTs in Phase II or III development that were carried out between 2021 and 2024. A thorough review of the US government database identified clinical trials of biologics and small molecule drugs for 14 agents in Phase I, 34 in Phase II, and 11 in Phase III that might be completed by 2028.

Individual-level metabolic connectivity from dynamic [18F]FDG PET reveals glioma-induced impairments in brain architecture and offers novel insights beyond the SUVR clinical standard.

This study evaluates the potential of within-individual Metabolic Connectivity (wi-MC), from dynamic [18F]FDG PET data, based on the Euclidean Similarity method. This approach leverages the biological information of the tracer's full temporal dynamics, enabling the direct extraction of individual metabolic connectomes. Specifically, the proposed framework, applied to glioma pathology, seeks to assess sensitivity to metabolic dysfunctions in the whole brain, while simultaneously providing further insights into the pathophysiological mechanisms regulating glioma progression. We designed an index (Distance from Healthy Group, DfHG) based on the alteration of wi-MC in each patient (n = 44) compared to a healthy reference (from 57 healthy controls), to individually quantify metabolic connectivity abnormalities, resulting in an Impairment Map highlighting significantly compromised areas. We then assessed whether our measure of metabolic network alteration is associated with well-established markers of disease severity (tumor grade and volume, with and without edema). Subsequently, we investigated disruptions in wi-MC homotopic connectivity, assessing both affected and seemingly healthy tissue to deepen the pathology's impact on neural communication. Finally, we compared network impairments with local metabolic alterations determined from SUVR, a validated diagnostic tool in clinical practice. Our framework revealed how gliomas cause extensive alterations in the topography of brain networks, even in structurally unaffected regions outside the lesion area, with a significant reduction in connectivity between contralateral homologous regions. High-grade gliomas have a stronger impact on brain networks, and edema plays a mediating role in global metabolic alterations. As compared to the conventional SUVR-based analysis, our approach offers a more holistic view of the disease burden in individual patients, providing interesting additional insights into glioma-related alterations. Considering our results, individual PET connectivity estimates could hold significant clinical value, potentially allowing the identification of new prognostic factors and personalized treatment in gliomas or other focal pathologies.

Rheumatic diseases and metabolism: where centre and periphery meet.

Over the past few decades, the connection between metabolism and various inflammatory and rheumatic diseases has been an area of active investigation. Nonetheless, the precise mechanisms underlying these relationships remain a topic of ongoing debate, owing in part to conflicting data. This discrepancy can be attributed to the predominant focus on peripheral mechanisms in research into the metabolic consequences of rheumatic diseases. However, a wealth of evidence supports the notion that the central nervous system, specifically the hypothalamus, has an important influence on metabolic homeostasis. Notably, links have been established between crucial hypothalamic mechanisms responsible for regulating energy balance (including food intake, thermogenesis, and glucose and lipid metabolism), such as AMP-activated protein kinase, and the pathophysiology of rheumatoid arthritis. This Review aims to comprehensively examine the current understanding of central metabolic control in rheumatic diseases and explore potential therapeutic options that target this pathophysiological mechanism.

Global research trends in endometrial receptivity from 2000 to 2024: bibliometric analysis

BackgroundIn recent years, extensive research has been conducted on endometrial receptivity (ER), with rapidly evolving research hotspots and trends. Our study aimed to explore the development of ER research from 2000 to the present and provide insights for future endeavors.Materials and methodsRelevant research publications on ER from 2000 to 2024 were retrieved from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and Excel tools were employed to conduct the bibliometric analysis.ResultsA total of 3,354 articles were analyzed, revealing an overall upward trend in annual publication numbers, signifying the increasing attractiveness and research value of this field. Globally, China led with a notable advantage of 1,030 publications, followed by the United States (650) and Spain (251), constituting the first tier of international research. Valencia University topped the list of institutions with 108 publications, closely followed by Shanghai Jiao Tong University with 87. Fertility and Sterility (IF6.6, Q1) is the one with the largest number of publications, accounting for 7.96% of the total publications. The three most co-cited journals were Fertility and Sterility, Biology of Reproduction, and Human Reproduction. A co-citation reference analysis revealed that ER research can be categorized into ten major subfields, including embryo implantation, frozen embryo transfer, integrins, recurrent implantation failure, intrauterine adhesions, etc. Since 2020, the keywords with the strongest citation bursts include repeated implantation failure and frozen.ConclusionThis study employs bibliometric analysis to offer researchers in the field of ER a comprehensive perspective. Since 2000, there has been a remarkable surge in the number of publications in the ER research field. These studies primarily concentrate on delving into the pathophysiological mechanisms of ER, with the primary objective of enhancing clinical pregnancy rates and live birth rates, benefiting more infertile patients. Currently, addressing the ER issues in patients with recurrent implantation failure represents the forefront of research. The primary treatment approaches currently in use involve optimizing embryo transfer timing and employing innovative strategies such as immunotherapy. These cutting-edge analyses not only provide new insights into the treatment of ER but also offer researchers fresh research directions, and staying abreast of the latest trends and advancements in the field.

Connecting the dots: A narrative review of the relationship between heart failure and cognitive impairment.

Large clinical data underscore that heart failure is independently associated to an increased risk of negative cognitive outcome and dementia. Emerging evidence suggests that cerebral hypoperfusion, stemming from reduced cardiac output and vascular pathology, may contribute to the largely overlapping vascular dementia and Alzheimer's disease. Despite these insights, cognitive outcomes remain largely overlooked in heart failure management. This narrative review outlines the prevalence and risk of cognitive impairment in heart failure patients, exploring potential shared pathophysiological mechanisms and examining the impact of heart failure therapy on cognitive deficits. Additionally, it discusses clinical implications and suggests future treatment approaches targeting therapeutic outcomes. Cognitive impairment is prevalent among individuals with heart failure, with reported rates varying widely depending on assessment methods. Shared pathological pathways and risk factors, including atrial fibrillation (AF), hypertension, obesity and type 2 diabetes mellitus, suggest a causal link. Mechanisms such as poor perfusion, microembolic events, ischaemic syndromes and cerebral inflammation contribute to this relationship. Moreover, heart failure itself may exacerbate cognitive dysfunction. This emerging understanding posits that vascular dementia and Alzheimer's disease may represent a pathophysiological continuum, driven by both the accumulation of misfolded proteins and cerebrovascular pathology due to cardiovascular dysfunction. Understanding these links is crucial for developing effective treatment strategies. The complex interplay between heart failure and cognitive impairment underscores the necessity for a holistic patient care approach. Both conditions share analogous disease processes, influencing self-management and independence in patients. Prioritizing brain health in heart failure management is essential to enhance patient prognosis and general well-being.