Progression Of Symptoms Research Articles

A 40‐week phase 2B randomized, multicenter, double‐blind, placebo‐controlled study evaluating the safety and efficacy of memantine in amyotrophic lateral sclerosis

AbstractIntroductionAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.AimsThis study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.MethodsA randomized, double‐blind, placebo‐controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in‐person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio and completed 36 weeks of treatment. The primary outcome of disease progression was assessed by the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS‐R), and blood was collected for biomarker analysis.ResultsOf the 99 participants enrolled in the study, 89 were randomized to memantine or placebo (ages 24–83 years, male‐to‐female ratio ~3:2). Fifty‐two participants completed the study treatment with no significant differences in disease progression, biomarker changes (including neurofilament light chain [NfL]), or neuropsychiatric testing noted between the groups. Initial NfL values correlated with the rate of ALSFRS‐R decline.DiscussionIn this study, memantine did not impact ALS disease progression or neuropsychiatric symptoms. Trials with remote enrollment may help trial participation and success.

Host genetics and gut microbiota influence lipid metabolism and inflammation: potential implications for ALS pathophysiology in SOD1G93A mice

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the progressive loss of motor neurons, with genetic and environmental factors contributing to its complex pathogenesis. Dysregulated immune responses and altered energetic metabolism are key features, with emerging evidence implicating the gut microbiota (GM) in disease progression. We investigated the interplay among genetic background, GM composition, metabolism, and immune response in two distinct ALS mouse models: 129Sv_G93A and C57Ola_G93A, representing rapid and slow disease progression, respectively.Using 16 S rRNA sequencing and fecal metabolite analysis, we characterized the GM composition and metabolite profiles in non-transgenic (Ntg) and SOD1G93A mutant mice of both strains. Our results revealed strain-specific differences in GM composition and functions, particularly in the abundance of taxa belonging to Erysipelotrichaceae and the levels of short and medium-chain fatty acids in fecal samples. The SOD1 mutation induces significant shifts in GM colonization in both strains, with C57Ola_G93A mice showing changes resembling those in 129 Sv mice, potentially affecting disease pathogenesis. ALS symptom progression does not significantly alter microbiota composition, suggesting stability.Additionally, we assessed systemic immunity and inflammatory responses revealing strain-specific differences in immune cell populations and cytokine levels.Our findings underscore the substantial influence of genetic background on GM composition, metabolism, and immune response in ALS mouse models. These strain-specific variations may contribute to differences in disease susceptibility and progression rates. Further elucidating the mechanisms underlying these interactions could offer novel insights into ALS pathogenesis and potential therapeutic targets.

Real-World, Observational, Retrospective Study to Evaluate the Effectiveness and Safety of Treatment with Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Sorafenib, the first drug to demonstrate survival benefits for advanced HCC, was validated through the SHARP randomized clinical trial (RCT). While RCTs are essential for assessing new therapies, real-world studies provide additional insights into their effectiveness in routine clinical practice. This study aimed to evaluate sorafenib’s real-world effectiveness by analyzing overall survival (OS) and the time to radiological and symptomatic progression. Methods: Data from 368 patients treated with sorafenib at a Brazilian Cancer Center between 2009 and 2020 were retrospectively reviewed. Results: The median OS was 9.6 months, and the time to radiological progression was 5.3 months, similar to the SHARP trial. However, the time to symptomatic progression was shorter (2.3 months) than the SHARP study (4.1 months). In terms of safety, 27.4% of patients presented clinically relevant toxicities, and 24.5% needed to discontinue treatment due to toxicity. Conclusions: Overall, sorafenib demonstrated effectiveness in the studied population, with OS and radiological progression times comparable to SHARP study results. The difference in symptomatic progression may be due to the study’s retrospective nature and limitations.

Association between the systemic immune-inflammation index and stress urinary incontinence: analysis using data from the National Health and Nutrition Examination Survey, 2007-2016

BackgroundInflammation plays a key role in the pathogenesis of stress urinary incontinence (SUI). The present study investigated the association between the systemic immune-inflammation index (SII) and SUI in a nationally representative adult population. MethodsData from the 2007-2016 National Health and Nutrition Examination Survey were analyzed. SUI was determined by self-report of urine leakage caused by activity such as coughing, lifting, or exercise. The SII was calculated as (platelet count × neutrophil count)/lymphocyte count. Survey-weighted logistic regression models were used to analyze the relationship between the SII and SUI. ResultsData from 18,797 participants, of whom 2695 (14.3%) reported SUI, were included. After adjusting for covariates, multivariate logistic models revealed that a high SII was associated with an increased overall likelihood of SUI (odds ratio [OR] 1.116 [95% confidence interval (CI) 1.018–1.223]; P = 0.0206). A higher risk was observed for monthly and weekly SUI (OR 1.144 [95% CI 1.009–1.297]; P = 0.0359, and OR 1.205 [95% CI 1.002–1.449]; P = 0.0478, respectively). Separate interaction analyses revealed no significant effects of age, gender, race, body mass index, marital status, alcohol use, or vigorous recreational activities on the association between the SII and SUI. ConclusionsResults revealed that a high SII associated with an increased risk for SUI. The SII may serve as a novel predictive biomarker in clinical practice to predict the occurrence and progression of SUI symptoms. A physiological mechanism underlying this relationship could be proposed and further evaluated in translational and basic scientific studies.

Riboflavin transporter deficiency, the search for the undiagnosed: a retrospective data mining study

BackgroundRiboflavin transporter deficiency (RTD) is an inborn error of riboflavin transport causing progressive neurological symptoms if left untreated. While infants with symptomatic RTD rapidly deteriorate, presentation later in childhood or in adulthood is more gradual. Symptoms overlap with more common diseases, carrying a risk of misdiagnosis, and given the relatively recent discovery of the genetic basis of RTD in 2010 it is likely that older patients have not been tested. Treatment with oral riboflavin (vitamin B2) halts disease progression and can be lifesaving. We hypothesized that patients may have been left unrecognized at the time of presentation and therefore we performed a datamining study to detect undiagnosed RTD patients in a tertiary referral hospital.MethodsA systematic search in Electronic Health Records (EHR) of all patients visiting the Amsterdam University Medical Centers between January 2004 and July 2021 was performed by a medical data text-mining tool. Pseudonymized patient records, matching pre-defined search terms (hearing loss or auditory neuropathy spectrum disorders combined with key clinical symptoms or riboflavin) were screened and included if no definitive alternative diagnosis for symptoms indicating possible RTD was found. Included patients were offered genetic testing. We documented total number of patients with possible RTD, number of patients that underwent genetic testing for RTD and results of genetic testing.ResultsEHR of 2.288.901 patients were automatically screened. Thirteen patients with possible RTD were identified and offered genetic testing. Seven patients chose not to participate. Genetic testing was performed in 6 patients and was negative. The datamining did detect all previously known RTD patients in the hospital.ConclusionsBy screening a large cohort of patients of all ages in a tertiary referral hospital in a period spanning 17 years, no new RTD patients were found. Although not all suspected patients underwent genetic testing, our findings suggest that the prevalence of RTD is low and the chance of having missed this diagnosis in a tertiary referral hospital is limited.

Lung transplantation for alpha-1-antitrypsin deficiency and Behçet's disease: A case report

INTRODUCTIONAlpha-1-Antitrypsin deficiency (A1ATD) is a genetically determined anti-proteinase deficiency which predisposes to early onset emphysema and liver disease. Lung transplantation (LTx) is the final therapeutic option. Behçet's disease (BD) is a rare autoimmune disease characterized by oral and genital ulcers, deep venous thrombosis associated with large and small-vessel vasculitis and aneurysms. The association of A1ATD and BD is unknown. We aim to describe a rare case of concomitant presentation of these pathologies in a patient submitted to LTx. CASE REPORTA 31-years-old female presented with oral and genital ulcers associated with cavernous sinus thrombosis in 2012, being diagnosed with BD. In 2018 debuted with progressive respiratory symptoms. CT-scan revealed extensive pulmonary emphysema associated with decreased pulmonary function. A1ATD was identified with a heterozygous “MZ” allelic combination. She was referred to LTx center in 2021. After additional investigation, the patient was considered to LTx. She underwent standard bilateral LTx in July of 2022. During post-operative time, special attention was given to the risk of vascular complications, and pos-operative angio-CT was performed actively searching for this possible outcome. Nevertheless, no major events occurred. After 1 year, she is fully functional with no signs of BD activity. CONCLUSIONTo our knowledge, this is the first description of LTx for A1ATD in a patient with BD, proving its feasibility in a highly selected patient at an experienced and specialized center. Nonetheless, solid organ transplantation in patients with BD remains a high risk procedure and should be indicated with caution.

The Progression of Symptoms in Post COVID-19 Patients: A Multicentre, Prospective, Observational Cohort Study

Background: Although the coronavirus disease 2019 (COVID-19) pandemic is no longer a public health emergency of international concern, 30% of COVID-19 patients still have long-term complaints. A better understanding of the progression of symptoms after COVID-19 is needed to reduce the burden of the post COVID-19 condition. Objective: This study aims to investigate the progression of symptoms, identify patterns of symptom progression, and assess their associations with patient characteristics. Methods: Within the P4O2 COVID-19 study, patients aged 40–65 years were recruited from five Dutch hospitals. At 3–6 and 12–18 months post COVID-19, medical data were collected, and pulmonary function tests were performed. In between, symptoms were assessed monthly with a questionnaire. Latent class mixed modelling was used to identify symptom progression patterns over time, with multinomial logistic regression to examine associations with patient characteristics. Results: Eighty-eight patients (aged 54.4 years, 48.9% males) were included. Three trajectories were identified for fatigue and dyspnoea: decreasing, high persistent, and low persistent. The odds of “decreasing fatigue” was higher for never smokers and participants in the lifestyle intervention and lower for those having a comorbidity. The odds of “decreasing dyspnoea” was higher for moderate COVID-19 patients and lifestyle intervention participants and lower for males, mild COVID-19 patients, and those with a higher age. Conclusions: Three distinct trajectories were identified for fatigue and dyspnoea, delineating patterns of symptom persistence following COVID-19. Sex, age, smoking status, participation in lifestyle interventions and COVID-19 severity were associated with the likelihood of belonging to different trajectories. These findings highlight the heterogeneity of the long-term symptoms experienced by post COVID-19 patients and emphasise the importance of personalised treatment strategies.

Walking biomechanics in women with patellofemoral osteoarthritis differ compared to men with and women without patellofemoral osteoarthritis

BackgroundDifferences in walking biomechanics between women and men with patellofemoral joint (PF) osteoarthritis (OA) may contribute to the development or progression of persistent symptoms in people with PFJ OA. ObjectiveEvaluate how walking biomechanics of women with PF OA differ from: (i) men with PFJ OA; and (ii) women without PF OA. Second, explore the relationship between knee-related symptoms/function and walking biomechanics in individuals with PF OA, and whether these are modified by sex. MethodsSixty-seven individuals with PF OA (43 women) and 14 women without PF OA were included. Biomechanics data were recorded during walking. Patient-reported symptoms and function were obtained using the Knee injury and Osteoarthritis Outcome Score. Differences in continuous biomechanical data were assessed using statistical parametric mapping, with discrete data and relationships evaluated using linear models. ResultsWomen with PF OA walked with a greater hip adduction angle throughout stance (t > 2.757) and lower impulses for the hip flexion, knee flexion, and ankle dorsiflexion moments (adjusted mean differences [95 % CI]:3.3 × 10–2 [-4.9 × 10–2, -1.6 × 10–2], -2.9 × 10–2 [-5.3 × 10–2, -0.4 × 10–2], -5.1 × 10–2 [-8.2 × 10–2, -2.0 × 10–2] Nms/kg, respectively) compared to men with PF OA. Compared to their asymptomatic peers, women with PF OA displayed a 5° offset towards greater hip flexion. Higher knee adduction moment impulse correlated with worse KOOS-ADL scores in men, not women. ConclusionObserved biomechanical differences were small in nature with moderate to weak relationship observed with the KOOS. Findings were not limited to the knee, indicating that women with PF OA display unique biomechanical features across the kinetic-chain.

Nirmatrelvir plus ritonavir reduces COVID-19 hospitalization and prevents long COVID in adult outpatients

Nirmatrelvir plus ritonavir received Emergency Use Authorization for treating mild to moderate COVID-19 in high-risk patients. Its efficacy against the Omicron variant of SARS-CoV-2 remains uncertain. This retrospective cohort study assessed the effect of nirmatrelvir–ritonavir in preventing severe disease progression and long COVID symptoms after acute COVID-19 in non-hospitalized adults. SALAMA medical records from Dubai’s COVID-19 healthcare centers between May 22, 2022, and April 30, 2023, were used to identify 7290 eligible patients, 9.6% of whom received nirmatrelvir–ritonavir. Treatment was associated with a notable reduction in COVID-19-related hospitalizations (adjusted hazard ratio [HR] of 0.39; 95% CI, 0.18–0.85) by day 28 of symptom onset. Moreover, nirmatrelvir–ritonavir was associated with fewer long COVID symptoms (adjusted HR of 0.42; 95% CI, 0.19–0.95). This suggests the significant effectiveness of nirmatrelvir–ritonavir against the Omicron variant, reducing both severe and long-term COVID-19 symptoms.

Rapid Deterioration and Fatal Outcomes in Colloid Cyst-Induced Obstructive Hydrocephalus: A Case Report

Introduction: Colloid cysts are rare intracranial tumors that can cause obstructive hydrocephalus, a potentially life-threatening condition. Despite being typically benign, they often present with insidious symptoms, leading to delayed diagnosis and catastrophic outcomes. Case Report: A 29-year-old woman presented with a two-month history of worsening headaches, nausea, and vomiting. Neuroimaging revealed a colloid cyst obstructing the third ventricle, resulting in hydrocephalus. Despite emergency placement of an external ventricular drain, the patient’s neurological condition deteriorated rapidly, culminating in brain death. Conclusions: This case highlights the critical importance of the early diagnosis and aggressive management of colloid cyst-induced hydrocephalus. The rapid progression of symptoms and devastating outcomes underscore the need for increased awareness among healthcare providers. Given the high mortality associated with this condition, further research is warranted to identify predictive factors and develop effective treatment strategies.

Platinum Resistance in Ovarian Cancer: Is This the End of the Line?

Approximately 80% of females with ovarian cancer are diagnosed with advanced disease, and around 70% of these females relapse within 3 years of first-line treatment. Five-year survival for newly diagnosed advanced ovarian cancer is less than 50%. Platinum-based chemotherapy is the cornerstone of systemic treatment; however, it is not appropriate for patients with relapsed ovarian cancer who had disease progression during previous platinum treatment, early symptomatic progression post-platinum treatment, or who are platinum intolerant. New drugs are needed to address the unmet need in patients with relapsed ovarian cancer who are not eligible for platinum-based chemotherapy. This article presents highlights from a satellite symposium conducted as part of the European Society for Medical Oncology (ESMO) Congress 2024, which took place from 13th–17th September 2024 in Barcelona, Spain. The objectives of the symposium were to improve understanding of the current treatment pathways and unmet needs for patients with ovarian cancer who are ineligible for platinum-based therapies, to raise awareness of the rationale for targeting folate receptor α (FRα) in a variety of novel therapeutics for platinum-resistant ovarian cancer (PROC), and to review the efficacy outcomes and side effects from recent clinical trials involving antibody–drug conjugates (ADC) in PROC. In this symposium, Ana Oaknin, Vall d’Hebron University Hospital, Barcelona, Spain, described the current landscape in advanced ovarian cancer and the unmet need in relapsed disease; Philipp Harter, Evangelische Kliniken Essen-Mitte, Germany, explored FRα-targeted therapeutics in PROC; and Kathleen Moore, Stephenson Cancer Center, University of Oklahoma, Norman, USA, discussed ADC development beyond FRα in PROC. The symposium concluded with a lively discussion, including questions from the audience, key examples of which are included in this article.

Deep brain stimulation halts Parkinson’s disease-related immune dysregulation in the brain and peripheral blood

Immune dysregulation in the brain and periphery is thought to contribute to the detrimental neurodegeneration that occurs in Parkinson’s disease (PD). Identifying mechanisms to reverse this dysregulation is key to developing disease-altering therapeutics for this currently incurable disease. Here we utilized the longitudinal data from the Parkinson’s Progression Marker Initiative to demonstrate that circulating lymphocytes progressively decline in PD and can be used to predict future motor symptom progression. Deep brain stimulation (DBS), which is used as a symptomatic treatment, could halt this progressive decline. By analyzing specific immune populations from a second cohort of patients, we could show that DBS causes a shift from the pro-inflammatory CD4+ T helper 17 cells driving neurodegeneration to anti-inflammatory CD4+ regulatory T cells. RNA-sequencing and immunohistochemistry in the brain of the A53T alpha-synuclein rat model of PD revealed that DBS also decreases neuroinflammation. These data suggest a potential disease-altering role for DBS by halting inflammatory processes.

Incidence and predictors of neuropsychiatric manifestations following a traumatic brain injury at referral hospitals in Dodoma, Tanzania: A protocol of a prospective longitudinal observational study.

Traumatic Brain Injury (TBI) is any injury to the brain resulting from an external force leading to complications. TBI affects 27-69 million people yearly, with high incidence in low- and middle-income countries (LMICs), mainly attributed to motor traffic accidents. Within three to six months following moderate-to-severe TBI, the relative risk of any psychiatric disorder is significantly higher than in the general population. Post-TBI neuropsychiatric disorders include depression with a prevalence of up to 53%, apathy up to 72%, Posttraumatic stress disorder (26%), anxiety (9%), manic symptoms (5-9%) and psychosis (3 to 8%). This study aims to determine the incidence and predictors of post-TBI neuropsychiatric manifestations among patients admitted at Referral hospitals in Dodoma. This is a prospective longitudinal observational study in which patients admitted with moderate to severe TBI will be recruited. Patients will be followed for six months, the diagnostic MINI International Neuropsychiatric Interview (MINI) tool will be used to assess TBI, and the severity and progression of symptoms will be evaluated using PHQ-9 for depressive symptoms, GAD-7 for anxiety symptoms, PCL-5 for Posttraumatic Stress Disorders (PTSD), MoCA for cognitive assessment, AES for apathy and YMRS for manic symptoms at one, three and six months. Logistic regression will be analysed to determine the association between predictors and neuropsychiatric outcomes. Given the dearth of understanding of the burden of neuropsychiatric complications and associated outcomes in sub-Saharan Africa, the study will shed light on the incidence and factors contributing to post-TBI neuropsychiatric complications and, thus, provide a platform for further research and design of necessary interventional programs for the population at risk.

Symptom assessment and angina classification of patients with ischemia and nonobstructive coronary arteries undergoing invasive coronary function testing: from the DISCOVER INOCA multicenter registry

Abstract Background Patients with ischemia and nonobstructive coronary arteries (INOCA) suffer from a broad range of anginal symptoms that may differ depending on the biologic sex of the patient, the underlying coronary vasomotor disorder, or the type of presentation. Purpose We sought to characterize the symptom description and angina classification of patients referred for invasive coronary function testing (CFT) in the DISCOVER INOCA multicenter registry, stratified by type of presentation (stable vs unstable), biologic sex, and underlying diagnosis, including coronary microvascular dysfunction (CMD), vasospastic angina (VSA), or other disorders such as symptomatic myocardial bridging. Methods DISCOVER INOCA is a prospective, multicenter registry in the United States that includes patients who are referred for clinically indicated coronary angiography and found to have INOCA. All patients underwent protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Symptom characteristics were compared between groups. Results From September 2022 until February 2024, 104 patients were enrolled, 78% were female, and mean age was 57 ± 11 years. The post-procedure diagnosis was CMD in 19%, VSA in 41%, a mixed syndrome in 15%, or other diagnosis in 26%. The average coronary flow reserve (CFR) was 2.9 ± 1.1 in the CMD group and 5.3 ± 3.0 in the VSA group, (p < 0.001). 53% of patients presented with stable angina and 47% with unstable or progressive symptoms. Symptoms included chest pain (89%), chest tightness (42%), chest pressure (39%), shortness of breath (53%), and fatigue (16%), and no significant differences were reported when stratified by diagnostic phenotype. Female patients were more likely to report arm/neck/back/jaw pain (25% vs 5% in men, p = 0.038). Symptom triggers included exertion/activity in 73%, emotional stress in 12%, and resting symptoms in 58%. In female patients 4% reported catamenial symptoms. Of patients with stable angina, the Canadian Cardiovascular Society (CCS) Angina Classification was Grade I in 25%, Grade II in 52%, Grade III in 21%, and Grade IV in 2%. In patients with unstable angina, the Braunwald Angina Classification was Class I in 9%, Class II in 73%, and Class III in 18%. Conclusions Patients with INOCA referred for clinically indicated coronary angiography and CFT were predominantly female and most commonly reported chest pain as a presenting symptom. Female patients were more likely to report arm/neck/back/jaw pain than male patients. Over half of patients reported resting symptoms with no differences between the diagnostic phenotypes (CMD, VSA, or other). The CCS and Braunwald angina classification indicated that most patients had moderate intensity symptoms. Patient-reported outcome measures will be used to systematically categorize the symptom burden in these patients.

Clinical significance of MRI-measured olfactory bulb height as an imaging biomarker of idiopathic Parkinson's disease.

This study aimed to determine whether the olfactory bulb height (OBH) measured using magnetic resonance imaging (MRI) has clinical utility as an imaging biomarker in the evaluation of patients with idiopathic Parkinson's disease (iPD) through its correlation with movement impairment. This retrospective study included cognitively intact patients with suspected parkinsonism. All participants underwent T2-weighted imaging to measure OBH. Logistic regression was used to determine whether OBH was an independent risk factor for distinguishing iPD patients from disease controls, and its relation with clinical parameters related to motor impairment, including clinical laterality, modified Hoehn and Yahr (HY) stage, and Unified Parkinson's Disease Rating Scale (UPDRS) III score, was investigated. Based on the final clinical diagnosis, 79 patients with iPD and 16 disease controls were included. The mean OBH was significantly smaller in iPD than in disease controls (p < 0.0001). OBH was a significant independent predictor of iPD, with a cutoff of 1.52 mm. In the comparison among the ipsilateral, contralateral side of iPD with clinical laterality, and disease control group, the OBH of the disease control group was significantly larger than both the ipsilateral and contralateral sides (P < 0.05). However, there was no significant difference in OBH between the ipsilateral and contralateral sides (p > 0.05). OBH according to HY stage was significantly smaller in HY stage 2-3 groups than in the disease control group (p < 0.001). The correlation analysis between UPDRS III and OBH showed a mild negative correlation (r = -0.32, p = 0.013). MRI-measured OBH is decreased in iPD regardless of age and sex and may be correlated with the progression of motor symptoms in the iPD.

Impaired striatal glutathione-ascorbate metabolism induces transient dopamine increase and motor dysfunction.

Identifying initial triggering events in neurodegenerative disorders is critical to developing preventive therapies. In Huntington's disease (HD), hyperdopaminergia-probably triggered by the dysfunction of the most affected neurons, indirect pathway spiny projection neurons (iSPNs)-is believed to induce hyperkinesia, an early stage HD symptom. However, how this change arises and contributes to HD pathogenesis is unclear. Here, we demonstrate that genetic disruption of iSPNs function by Ntrk2/Trkb deletion in mice results in increased striatal dopamine and midbrain dopaminergic neurons, preceding hyperkinetic dysfunction. Transcriptomic analysis of iSPNs at the pre-symptomatic stage showed de-regulation of metabolic pathways, including upregulation of Gsto2, encoding glutathione S-transferase omega-2 (GSTO2). Selectively reducing Gsto2 in iSPNs in vivo effectively prevented dopaminergic dysfunction and halted the onset and progression of hyperkinetic symptoms. This study uncovers a functional link between altered iSPN BDNF-TrkB signalling, glutathione-ascorbate metabolism and hyperdopaminergic state, underscoring the vital role of GSTO2 in maintaining dopamine balance.

Angiographically occult spinal dural arteriovenous fistula diagnosed by exploratory surgery with intraoperative ultrasound: illustrative case.

A 78-year-old male presented with progressive myelopathic symptoms. The clinical course and imaging findings raised a high suspicion for venous hypertensive myelopathy due to a spinal dural arteriovenous fistula (SDAVF). Magnetic resonance angiography and four complete spinal angiograms did not reveal the presence of an SDAVF. Despite multiple negative angiograms, intraoperative ultrasound revealed abnormal cord edema and arterialized pulsatile vessels, confirming the presence of an SDAVF. The fistula was found and cauterized, which resulted in a decrease in the caliber of the dilated veins and an observed reduction of spinal cord stiffness posttreatment. The patient exhibited gradual improvement in neurological function. Retrospective analysis of the multiple complete spinal angiograms failed to reveal an anomaly at the treated level or any other level. This case underscores the diagnostic utility of intraoperative Doppler ultrasound and the importance of maintaining a high index of suspicion for SDAVF in cases with consistent clinical characteristics and a lack of alternative diagnoses, even with negative spinal angiography. https://thejns.org/doi/10.3171/CASE24438.

International and intercultural training on the use of Art Therapy for Dementia Care

Abstract In 2023 more than 55 million people had dementia worldwide, with nearly 10 million new cases every year. Currently art therapy has been widely adopted in the assistance of people with dementia because of the positive outcomes in terms of reducing depressive and behavioural symptoms and of improving the patients’ overall quality of life. In literature there was a knowledge gap on social and health professionals’ training for being able to effectively use art therapy in relation with different origins of people with dementia in a multi-ethnic world. This research aimed to assess the impact of promoting joint international and intercultural training session for social workers and health professionals’ students. The used methodology was a prospective research-intervention study with the conductions of two seasonal schools (Florence - Italy in July and Ankara - Tukey in October 2023) on the use of art therapy in the different stages of dementia disease within the Erasmus+ Project DementiaCare (2021-1-TR01-KA220-HED-000027648). Each seasonal school was attended by 25 students from Italy (5), Portugal (5), Slovenia (5), and Turkey (10) to ensure an international and intercultural approach. Pre- and post- test results showed the increased knowledge of students on the theoretical notions on dementia care and art therapy. Positive opinion on the projects developed by mixed group of students (with representants of the 5 involved universities) manifested the enforcement of their relational competences and skills mutually adapting their way of doing and communication register to the multi-ethnic and multi-cultural group’s needs. Evidence showed how mutual knowledge among social and health professionals with different cultures and their joint training allowed these professionals to be able to provide an integrated and effective assistance to every patient with dementia, personalizing assistance according with their different traditions and historical memories. Key messages • Art therapy has been adopted as non-pharmacological approach in dementia care to mitigate progression of symptoms’ severity, serving as alternative tool for self-expression for patients. • Conducting joint international and intercultural training sessions for social and health professionals in art therapy enabled them to develop a respectful, multi-ethical approach to dementia care.

Echocardiographic insights redefining risk in pulmonary arterial hypertension: a focus on right atrial volume index for enhanced stratification

Abstract Introduction In Pulmonary arterial hypertension (PAH), the right atrium plays a critical role, and its size, determined by echocardiography, is crucial for risk stratification. Despite this, current guidelines still prioritize right atrial area (RAA) over the right atrial volume index (RAVI). This approach is contrary to the recommendations of international echocardiography societies since 2016, which advocate for the use of RAVI for a more accurate assessment. Purpose Identify the RAVI value corresponding to the RAA, in PAH risk stratification used in the 2022 ESC guidelines. Methods We conducted a retrospective analysis of all consecutive patients of a single-center, since 2002. Patient's echocardiograms were revised for simultaneous assessment of RAA and right atrial volume index (RAVI). Over an average follow-up of 6.7 years (SD 5.9), we recorded a cohort of 82 patients diagnosed with PAH. From this group, we excluded 27 patients with congenital etiologies, 14 due to the insufficient quality of echocardiographic data, and one patient identified as an extreme statistical outlier. A Pearson's correlation analysis was used to access the correlation between RAA and RAVI for PAH diagnosis. Results A total of 40 patients were included with a mean age at diagnosis of 48.85 years (SD 17.82), predominantly female (77.5 %). The most prevalent etiologies were idiopathic (32.5%) and connective tissue disease-associated PAH (27.5%). Clinical presentations included right heart failure signs in 30% of patients, rapid symptom progression in 12.5%, syncope history in 15% and 77.5% in WHO-FC III-IV. Average 6-MWD and NT-proBNP levels were 392,1 m (SD 120,2) and 1636,18 ng/L (SD 2576,14), respectively. Average hemodynamics parameters were right atrial pressure 7,39 mmHg (SD 4,940); cardiac index 2,28 L/min/m2 (SD 2,06); stroke volume index 3,38 mL/m2 (SD 3,92) and mixed venous oxygen saturation 65,68% (SD 10,86). Average echocardiographic parameters were RAA 20,14 cm2 (SD 4,80); TAPSE/sPAP 0,34 mm/mmHg (SD 0,18) and RAVI 37,78 mL/m2 (SD 13,67), with 10% of pericardial effusion. Statistical analysis revealed a strong and significant correlation between RAA and RAVI (r=0.82, 95% CI: 0.69-0.90, p&amp;lt;0.001). The derived linear relationship is expressed as "y=2.8*X -18". Therefore, an RAA value of 18 cm² translates to a RAVI of 32 mL/m², while an RAA of 26 cm² corresponds to a RAVI of 55 mL/m². Conclusion Our study supports a revision in HAP risk assessment guidelines, suggesting a shift to a more comprehensive approach using right atrial volume index (RAVI) measurements. We propose categorizing risk as low for RAVI &amp;lt; 32 mL/m², intermediate for RAVI between 32 and 55 mL/m², and high for RAVI &amp;gt; 55 mL/m². This recommendation aligns with the standards of international societies and is grounded in best clinical practices, considering that indexing measurements of the right atrium to body size potentially offers greater accuracy than absolute values.

In silico identification and characterisation of pathogenic genetic variants (nsSNPs) in the eukaryotic initiation factors eIF2 and eIF2B affecting miRNA binding sites

BackgroundThe eukaryotic translation initiation factors (eIF2 and eIF2B) are known to play a regulatory role in translation initiation. Studies have indicated that several missense mutations in both eIF2 and eIF2B subunits can lead to severe neurological diseases and cancer. In the current study, we have attempted to identify and characterise the single-nucleotide polymorphisms (SNPs) in the said subunits and their correlation with various diseases.ResultsInterestingly, we could identify SNPs only in 3′ untranslated regions (3′UTR) from EIF2 (EIF2S1 and S3) and EIF2B (EIF2B1, B2 and B5 subunits). Of which, two SNPs, one in each EIF2B1 (rs1050448) and EIF2B2 (rs4556), are observed to be affecting miRNA binding sites. The gene ontology (GO) analysis of identified miRNAs indicates their association with central nervous system development, various stress responses, growth factors, and immune system signalling pathways. Furthermore, molecular docking studies also confirm that the identified miRNAs have an excellent binding ability with corresponding wild-type/mutant dsDNA and mRNA with HADDOCK binding scores in the range of − 38.78 to − 3.99 kcal/mol and − 86.47 to − 23.78 kcal/mol, respectively.ConclusionWe conclude that the identified miRNAs may play a regulatory role in the symptomatic progression of neurological disorders and cancer and the same is validated by existing experimental evidences. Overall, the identified miRNAs serve as potential candidates for carrying out clinical investigations.Graphical abstract