Parkinson's Disease Group Research Articles

Long-term Assessment of Speech and Swallowing Function in Laryngopharyngeal Cancer Patients After J-Flap Reconstruction.

A novel J-shaped anterolateral thigh (ALT) flap reconstruction technique had been developed to simultaneously restore swallowing and speech functions in patients following total laryngopharyngectomy. This study aimed to assess the outcomes and surgical complications in patients who underwent J-flap reconstruction over time. Patients who underwent J-shaped ALT flap phonatory tube reconstruction were enrolled. Surgical morbidities and outcomes were evaluated every 3 months postsurgery for 12 months or death. Of the 36 patients, 13 underwent circumferential pharyngeal wall resection (circumferential defect group, CD group), and 23 underwent partial resection (partial defect group, PD group). After 12 months, 97% of the patients resumed oral intake without reliance on a nasogastric tube (NG tube), and 50% achieved fluent speech using the reconstructed phonatory tube. The CD group showed a higher rate of delayed healing (30.77% vs. 0%, p=0.005). The PD group exhibited significantly greater percentages of individuals consuming solid food at both the 3- and 12-month intervals than the CD group (81.0% vs. 23.1% and 78.9% vs. 40%, respectively). : This study examined the evolution of speech and swallowing functions over time following J-flap voice tube reconstruction. Regardless of whether the defect was circumferential or partial, using a J-shaped ALT flap phonatory tube effectively restored both speech and swallowing functions, offering long-lasting benefits.

Aging, not Parkinson’s disease, decreases a recalibration of body ownership caused by vision-respiratory interaction

IntroductionRecalibration of body ownership perception occurs through an integration among multiple modalities. A recent study has shown that respiratory rhythm also causes the recalibration of ownership perception. However, the risk factors influencing the recalibration of ownership perception caused by vision-respiratory interaction remain unclear. In this study, focusing on aging and Parkinson’s disease (PD), we examined the effects of those risk factors on the recalibration.MethodsBy applying the rubber hand illusion (RHI), which temporarily alters ownership perception, and using a device that synchronizes the respiratory rhythm with the movement of a mannequin hand, we measured a change in ownership perception in RHI training by vision-respiratory interaction. The changed ownership was compared among the elderly healthy, PD, and young healthy groups.ResultsThe results showed no difference in the changed ownership between the elderly healthy and PD groups, while the two groups decreased the change in the ownership perception compared to the young healthy group.DiscussionThe finding suggests that aging, not PD, related to the recalibration of ownership perception by vision-respiratory interaction. An anomaly in body perception due to aging may be associated with a mechanism in which respiratory rhythm affects the adaptation of body representations.

Diagnostic Potential of NEAT1, hsa-let-7a-5p, and miR-506-3p in Early-stage Parkinson's Disease.

Parkinson's disease (PD) is a multifaceted disease that is influenced by both genetic and environmental parameters. Non-coding RNAs have been shown to be ideal biomarkers for several diseases, including PD. This study was conducted to evaluate the expression levels of NEAT1, hsa-let-7a-5p, and miR-506-3p in individuals with PD to assess their efficacy for early-stage PD diagnosis. Twenty-four patients with PD and 29 healthy individuals participated in this study. The IntaRNA tool was used to predict potential base pairings between NEAT1 and let-7a-5p, and NEAT1 and miR-506-3p. RT-qPCR was employed to measure the relative expression of tyrosine hydroxylase (TH), as well as nuclear enriched abundant transcript 1 (NEAT1), hsa-let-7a-5p, and miR-506-3p levels in both groups. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the diagnostic value. The PD group exhibited significantly elevated NEAT1 expression levels compared to the healthy control group. While the PD group exhibited an insignificant decreased TH expression level relative to the healthy group. Furthermore, the levels of hsa-let-7a-5p and miR-506-3p expression were seen to be decreased in patients with PD in comparison to the control group. Integration of NEAT1, hsa-let-7a-5p, and miR-506-3p levels significantly enhanced diagnostic capabilities and increased the AUC to 0.9501 (95% confidence interval: 0.8978-1.000, p < .0001). The elevated NEAT1 expression and the decreased expression of hsalet- 7a-5p and miR-506-3p in PD patients indicate that these factors might contribute to the disease's pathogenesis. Combining the ROC curves of NEAT1 and hsa-let-7a-5p with miR-506-3p showed improved sensitivity and specificity, facilitating more accurate PD diagnosis. More importantly, they may contribute as promising non-invasive biomarkers for PD diagnosis.

Dopamine transporter availability based on white matter hyperintensity during early to mid-stage Parkinson's disease and multiple system atrophy: a case control study.

To evaluate the association of white matter hyperintensity (WMH) with dopamine transporter (DAT) availability in patients with early to mid-stage parkinson's disease (PD) and multiple system atrophy (MSA). The clinical and imaging data of 55 patients were collected, including 38 PD and 17 MSA patients and the clinical features of the two groups were compared. DAT specific binding ratio (SBR) were compared between severe and non-severe WMH groups, and between PD and MSA groups. The relationships of WMH with DAT availability and basic clinical characteristics were analyzed. Multiple linear regression analysis showed that age was the only significant variable showing correlation WMH. Age was the only clinical variable significantly correlated with WMH in PD patients (coefficient for periventricular white matter hyperintensity: 0.430, P = 0.007; coefficient for deep white matter hyperintensity: 0.381, P = 0.018). There was no significant correlation between WMH and SBRs and age in MSA patients. The SBR of the caudate nucleus and anterior putamen was significantly lower in the severe WMH group of patients than in the non-severe WMH group (P < 0.05). The values of the caudate nucleus, anterior putamen, and anterior putamen/posterior putamen were significantly lower in PD patients with than without severe WMH (P < 0.05), and the damage to the striatal DAT in MSA patients with severe WMH was similar to the non-severe patients (P>0.05). Patients with PD and a high WMH score had lower DAT availability. WMH affected the availability of DAT in patients with early to mid-stage PD compared to MSA.

Cardiovascular risk factors in poly-vascular vs isolated lower extremity peripheral arterial disease. analysis from the SOLACI peripheral registry

Abstract Introduction Atherosclerotic disease in more than one vascular bed (Polyvascular disease), is a strong independent risk factor for ischemic events and has worse clinical outcomes than those with disease in a single territory. Aims The objective of the present interim analysis is to describe the differences in cardiovascular risk factors and clinical presentation between patients with isolated infra-aortic peripheral artery disease (lower limb: "LL-PAD") and patients with Polyvascular Disease ("PD": simultaneuous coexistence of LL-PAD and affection of at least one more vascular bed) from a cohort of patients undergoing LL endovascular procedures in Latinamerica. Methods Our cohort included patients from The SOLACI Peripheral Registry from March 2021 to February 2024 (a prospective, multi-center, observational, and hospital-based registry of patients with LL- PAD, treated with endovascular interventions across 10 Latin American countries, 42 centers). Patients were considered to have PD if besides LL-PAD, they had a documented history of previous myocardial infarction (MI), coronary revascularization, cerebrovascular, aortic, and/or carotid artery disease. Results A total of 1438 patients were included in the analysis. PD was present in 506 patients(35.1%), of which 225(44.5%) had previous MI; 296(58.5%) previous coronary revascularization;265(52.4%) had aortic and / or carotid disease; and 121(23.9%) had cerebrovascular disease. Patients with PD were older than those with LL-PAD(70.5±9.76 vs 68.6±10.7). PD was more prevalent in men(69.6% vs 62.4%), former smokers(48.2% vs 32.8%), hypertension(92.1% vs 80.5%) and patients with dyslipidemia(75.3% vs 64%). The distribution of treated lesions in the PD group was: 15.4% ilio-femoral; 34 % femoropopliteal; 23.3% infrapopliteal; and 24% had multiple peripheral territories affected and treated at the same time-point. In the LL-PAD group, the distribution of treated lesions was: 12.5% ilio-femoral; 28.6% femoropopliteal; 31.5% infrapopliteal; and 24.8% had multiple peripheral territories affected simultaneously and treated during the same procedure. In general, the lesions were shorter in the PD group: ilio-femoral(53.5±29.2 vs 66.7±48.2mm); femoropopliteal(119±73.6 vs 122±81.7mm); and infrapopliteal(129±83.1 vs 147±93.1mm). In the PD group, a higher percentage of patients were treated with statins and antithrombotic agents: statins (87.5% vs 70.8%), aspirin (91.5% vs 81.1%), clopidogrel (60.9% vs 40.1%), and oral anticoagulants (13.8% vs 6.5%). The use of rivaroxaban was similar in both groups (3.4% vs 3.9%). The PD group had higher intrahospital complication rates: intrahospital death (2.2% vs 0.8%), cardiovascular intrahospital death (1.2% vs 0.4%), MI (0.8% vs 0.1%), stroke (0.4% vs 0%) and bleeding (0.8% vs 0.9%). Conclusions Patients with PD represent a very high-risk population. Systematic screening of multiple vascular beds in patients with LL-PAD may be warranted to prevent worse outcomes.

Peripheral biomarkers of Parkinson’s disease and its correlation with clinical symptoms: a case-control study

BackgroundInflammation significantly impacts Parkinson’s disease (PD), yet the intricate relationship between inflammatory markers and PD remains elusive.ObjectiveTo identify the peripheral biomarkers of PD and its correlation with the motor and non-motor symptoms of PD.Methods79 PD patients and 65 controls were included in this study. Clinical information and the serum levels of IL-8, IL-27, IL-33, β-NGF, AgRP, and TRAILR2 in the participants were collected. Appropriate scales were used to assess the symptoms of PD. For the factors with significant differences in the two groups, multivariable logistic regression was used to determine its relationship with PD. Moreover, spearman correlation was conducted to explore the correlation between the factors and PD related symptoms. The IL-27 level was compared between the cognitively healthy PD group and the mild cognitive impairment in PD (PD-MCI). The serum level of TRAILR2 was positively correlated with age and was not associated with other clinical characteristics related to PD.ResultsCompared to controls, the serum levels of IL-27(P = 0.013) were increased whereas the levels of TRAILR2(P = 0.008) were decreased in PD patients. IL-8, IL-33, β-NGF, and AgRP showed no significant differences between the two groups. After controlling for the other variables, IL-27 was considered as an independent risk factor for PD in the multivariable logistic regression model. The receiver operating characteristic (ROC) curve for diagnosing PD with IL-27 yielded an area under the curve (AUC) of 0.621. Additionally, IL-27 level in PD patients was positively correlated with age, the disease duration, LEDD and negatively correlated with the MoCA scores. However, no significant difference was found in IL-27 levels between cognitively healthy PD and PD-MCI groups.ConclusionElevated serum IL-27 was a risk factor for PD and positively correlated with the cognitive decline in PD.

Sleep Quality in Parkinson Disease: Clinical Insights and PSQI Reliability Assessment

AbstractSleep disturbances are prevalent in Parkinson disease (PD), encompassing a spectrum from parasomnias like REM sleep behavior disorder to symptoms of sleep-wake cycle dysregulation, such as insomnia and daytime sleepiness. This research investigates sleep quality in PD patients compared with a matched healthy control group and explores the relationships between PD clinical characteristics and sleep parameters. Additionally, the study assesses the reliability of the Pittsburgh Sleep Quality Index (PSQI) for PD patients by examining internal consistency. The study comprises 52 participants, 27 in the PD group and 25 in the healthy control group, matched for sex and age. Sleep quality revealed that PD patients experienced significantly poorer sleep quality than the control group (p = 0.009). Weak correlations were found between PSQI scores and the modified Hoehn and Yahr scale (p = 0.062), with no correlation observed with the daily equivalent dose of levodopa (L-DOPA). The prevalence of poor sleep quality (PSQI score &gt; 5) was 85.1% for PD patients and 68% for the control group. The internal consistency analysis of the PSQI yielded a Cronbach's α of 0.588 for the PD group. While the PSQI demonstrates utility in detecting general sleep abnormalities and gauging patient perceptions of sleep quality in PD, its limitation as a global score is emphasized. The index prioritizes sleep habits and may not fully capture important sleep disorders in this population. These findings underscore the complex relationship between PD and sleep quality, suggesting the need for a comprehensive approach to assess and address sleep disturbances in PD patients.

Application of optical coherence tomography in neurodegenerative diseases: a focus on Parkinson’s, Alzheimer’s, and Schizophrenia in Bulgarian patients

This study investigates retinal alterations in patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and schizophrenia (SZ) using Optical Coherence Tomography (OCT). The primary objective was to determine whether these neurodegenerative diseases manifest in measurable retinal changes and to assess the impact of disease duration, medication use, and cognitive decline on these alterations. A cross-sectional observational design was employed, including 132 patients and age- and gender-matched controls. OCT imaging was performed using the Topcon 3D OCT-1 Maestro 2, focusing on the retinal nerve fibre layer (RNFL), ganglion cell complex (GCC), and macular thickness. Significant retinal thinning was observed in the AD and PD groups, correlating with disease severity and cognitive decline, and was more pronounced with longer disease duration. In contrast, no significant retinal changes were identified in the SZ group. The study also explored the effects of different drug classes, revealing correlations between specific medications and retinal parameters, particularly in the AD and PD cohorts. To our knowledge, this is the first study of its kind conducted with Bulgarian patients. These findings suggest that OCT may serve as a non-invasive biomarker for neurodegeneration in AD and PD, though its utility in SZ remains limited. Future research should aim to standardize OCT protocols, further investigate the potential of retinal imaging in tracking neurodegenerative disease progression, and explore its integration with other neuroimaging techniques for a more comprehensive diagnostic and monitoring approach.

Reaching and stepping respond differently to medication and cueing in Parkinson’s disease

The basal ganglia contribute to internal timekeeping, and dopaminergic medication has been observed to moderate timing deficits associated with Parkinson’s Disease (PD) during single joint movements. However, it is unclear whether similar effects can be observed in multi-joint movements. Twenty-five people with PD and twelve healthy peers performed repetitive reaching and stepping-in-place tasks with and without auditory cues at their self-selected maximal cadence. The PD group was measured ON and OFF medication. Reduced cadence error was found for both groups and tasks when cued, and ON PD exhibited decreased cadence compared to OFF PD. Overall timing variability was no different from controls, but differences were found in estimates of clock and motor variance using the Wing-Kristofferson model of interval timing. A medication and cueing interaction during the reaching task produced increased clock variance in uncued, ON PD. During the stepping task, clock and motor variance of the PD group were unaffected by cues, in contrast to the control group. Serial lag-one correlation was reduced in both groups for cued reaching, but was unaffected by cueing or medication in the PD group when stepping-in-place. These findings suggest that overall timing variability may not capture timing deficits in PD.

Disgust-specific Impairment of Facial Emotion Recognition in Parkinson's Disease Patients with Mild Cognitive Impairment.

This study investigated the association between cognitive function and facial emotion recognition (FER) in patients with Parkinson's disease (PD) and mild cognitive impairment (PD-MCI). We enrolled 126 participants from Taiwan, including 63 patients with idiopathic PD and 63 matched healthy controls. The PD group was divided into two groups: those with normal cognitive function (PD-NC) and those with MCI (PD-MCI). Participants underwent a modality emotion recognition test and comprehensive cognitive assessment. Our findings reveal that patients with PD-MCI exhibit significantly impaired FER, especially in recognizing "disgust," compared with patients with PD-NC and healthy adults (p = .001). This deficit correlates with executive function, attention, memory, and visuospatial abilities. Attention mediates the relationship between executive function and "disgust" FER. The findings highlight how patients with PD-MCI are specifically challenged when recognizing "disgust" and suggest that cognitive training focusing on cognitive flexibility and attention may improve their FER abilities. This study contributes to our understanding of the nuanced relationship between cognitive dysfunction and FER in patients with PD-MCI, emphasizing the need for targeted interventions.

Circumferential patellar denervation does not reduce anterior knee pain in total knee arthroplasty without patellar resurfacing; a prospective comparison

BackgroundThis study aimed to evaluate the effectiveness of circumferential patellar denervation in reducing anterior knee pain (AKP) and improving clinical outcomes after total knee arthroplasty (TKA) without patellar resurfacing.Materials and methodsThis prospective, non-randomized, observational study included patients who underwent primary TKA at our institution between August 2023 and January 2024. Patients were divided into two groups: those who received patellar denervation (PD group) and those who did not (NPD group). The primary outcome was the reduction in anterior knee pain (AKP), measured by the Visual Analog Scale (VAS). Secondary outcomes included the Kujala Knee Score, Western Ontario and McMaster Universities Arthritis Index (WOMAC), and range of motion (ROM). Assessments were conducted preoperatively and at 3 and 6 months postoperatively.ResultsFour patients in the PD group and five in the NPD group were excluded from the study due to failure to complete follow-up. Thus, 74 female and 16 male patients with a mean age of 67.4 ± 4.2 years were included in the final analysis. There were no significant differences between the two groups with respect to age, sex, side of surgery, height, weight, BMI, grade of patellofemoral osteoarthritis, preoperative ROM, VAS score, Kujala score, and WOMAC score (p: n.s. for all variables). No significant differences were found between the groups for VAS, Kujala, and WOMAC scores at any time point (p: n.s.). Significant improvements in these scores over time were indicated by repeated measures ANOVA (p = 0.001 for both groups). Pairwise comparisons showed significant improvements from preoperative to postoperative months three and six and from postoperative months three to six (p = 0.001 for all comparisons). Both groups experienced decreased knee ROM at third month, which returned to preoperative values at sixth month with no significant differences. No complications were observed during the study.ConclusionsCircumferential patellar denervation does not provide additional benefit in reducing anterior knee pain or improving functional outcomes compared to the non-denervation approach in TKA without patellar resurfacing.Level of evidenceLevel III, Prospective comparative study.

Can We Differentiate Between Organic and Functional Bladder Outlet Obstruction in Males With Parkinson's Disease?

To determine the type of bladder outlet obstruction (BOO) in patients with Parkinson's disease (PD). A case-control study was carried out in 46 patients divided into two groups. Group 1 formed by 23 PD patients with BOO (a URA parameter ≥ 29 cm H2O). Group 2 formed by 23 patients with benign prostatic hyperplasia (BPH) and compressive obstruction (an opening pressure > 35 cm H2O) and URA parameter ≥ 29 cm H2O). Both groups underwent a pressure-flow study to calculate Dynamic Urethral Resistance Relationship (DURR) patterns. Based on previous research, we describe two types of DURR pattern. Pattern A typical of dynamic or functional obstruction and pattern B typical of static or organic obstruction. We found that PD patients had a significantly higher frequency of pattern A (70%) than BPH patients (4%). Other significant differences between groups were age (greater in PD group), bladder compliance (greater in PD group), maximum flow rate [Qmax (greater in BPH group)], maximum detrusor pressure [Pmax (greater in BPH group)], detrusor pressure at maximum flow rate [PQmax (greater in BPH group)], opening detrusor pressure (greater in BPH group), and the bladder contractility parameters BCI and Wmax (greater in BPH group). There were no significant differences in perineal voiding electromyography (EMG) activity between groups nor relationship between voiding EMG activity and the type of DURR pattern. Our results are consistent with the usefulness of the DURR pattern to differentiate between functional and organic BOO in PD patients. Most PD patients have functional obstruction although a minority has organic obstruction consistent with BPH.

Endoscopic Management of Post-Esophagectomy Delayed Gastric Conduit Emptying (DGCE): Results from a Cohort Study in a Tertiary Referral Center with Comparison between Procedures

Background/Objectives: Delayed gastric conduit emptying (DGCE) occurs in 15–39% of patients who undergo esophagectomy. Intra-Pyloric Injection of Botulinum Toxin (IPBT), Pneumatic Balloon Dilation (PBD), and the same session combination (BTPD) represent the main endoscopic procedures, but comparative data are currently unavailable. Methods: We retrospectively analyzed prospectively collected data on all consecutive patients with DGCE treated endoscopically with IPBT, PBD, or BTPD. ISDE Diagnostic Criteria were used for DGCE diagnosis and classification. A Gastric Outlet Obstruction Score was used for clinical staging. All patients undergoing IPBT received 100 UI of toxin, while those undergoing PBD were dilated up to 20 mm. Clinical success (CS) was defined as the resolution of symptoms/resumption of feeding at discharge or expanding dietary intake at any rate. Recurrence was defined as symptom relapse after more than 15 days of well-being requiring endoscopic/surgical intervention. Results: A total of 64 patients (81.2% male, 90.6% Ivor-Lewis esophagectomy, 77.4% adenocarcinoma) with a median age of 62 years (IQR 55–70) were enrolled: 18 (28.1%) in the IPBT group, 24 (37.5%) in the PBD group, and 22 (34.4%) in the BTPD group. No statistically significant differences were found in the baseline characteristics, surgical techniques, and median follow-up among the three groups. BTPD showed a higher CS rate (100%) compared to the PD and BTPD groups (p = 0.02), and a Kaplan–Meier analysis with a log–rank test revealed that the BTPD group was associated both with a significatively shorter mean time to refeed of 1.16 days (95% CI 0.8–1.5; p = 0.001) and a shorter median time to discharge of one day (95% CI 1–3; p = 0.0001). Conclusions: Endoscopic management of DGCE remains challenging. Waiting for further strong evidence, BTPD can offer patients a higher clinical efficacy rate and a shorter time to refeed and be discharged.

Assessment of Sexual Dysfunction in Male Patients with Young-Onset Parkinson’s Disease: A Case-Control Study

Introduction: There is a need for a comprehensive assessment of sexual dysfunction in patients with young-onset Parkinson’s disease (PD) to better understand its impact on this population. This study aimed to assess sexual dysfunction in patients with young-onset PD. Methods: This case-control study was conducted using a self-administered International Index of Erectile Function Scale (IIEF) questionnaire. The questionnaire included questions related to sexual function, including the ability to achieve and maintain erection and sexual desire. The participants included 30 individuals with young-onset PD and 30 controls without PD who were matched for age and gender. Results: The study enrolled 30 patients with an average age of 37.2 ± 5.29 years and PD symptom duration ranging from less than two years to over two years. Most patients were classified as having stage 2 or 3 PD and exhibited a range of symptoms, such as bradykinesia, tremors, rigidity, and postural instability. The findings revealed that 40% of the PD group experienced moderate erectile dysfunction, while 23.33% reported severe dysfunction, in contrast to the absence of dysfunction observed in the control group. The analysis indicated that patients with a disease duration of less than two years had higher scores across all five components of the IIEF questionnaire. Furthermore, anxiety, depression, increased medication use, and disease severity significantly affected sexual function. Conclusion: This study highlights the impact of young-onset PD on sexual function and underscores the importance of the early recognition and management of sexual dysfunction in patients with PD.

Monocyte to high-density lipoprotein cholesterol ratio reflects the peripheral inflammatory state in parkinsonian disorders

BackgroundIn Parkinson’s disease (PD) and Parkinson plus syndrome (PPS), inflammation is recognized as a relevant or contributing factor in the advancement of the diseases. For this reason, numerous biomarkers signaling immune alteration in both the central and peripheral nervous systems have been evaluated in PD and PPS. Nonetheless, the comprehensive inflammatory indices derived from readily available standard blood tests in PD, PPS, and healthy controls (HC) were rarely evaluated especially in the early stage of the diseases. ObjectiveThe aim of this study is to explore the serum level of peripheral inflammatory markers among the patients and investigate whether these markers contribute to symptoms. MethodClinical data and blood test results from drug naïve, early-stage 139 PD and 87 PPS patients, along with 139 age- and sex-matched healthy controls (HC) to PD were enrolled, with exclusion criteria applied to conditions potentially affecting inflammation. The study examined the disparities in peripheral inflammation among the groups, using total and subpopulation of white blood cells (WBCs), platelet count, red cell distribution width (RDW), high-density lipoprotein cholesterol (HDL-C), and other composite values reflecting inflammation including RDW to platelet ratio (RPR), neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio (PLR), neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), platelet to HDL-C ratio (PHR), systemic inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI). ResultThe MHR values were significantly higher in both PD and PPS groups compared to HC (p < 0.001), and NHR was significantly higher in the PPS group only compared to the HC group (p < 0.001). However, no significant differences in all the inflammatory markers were observed between PPS and PD (p > 0.05). Subgroup analysis of progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) patients revealed significantly higher NHR and MHR levels compared to the HC group (p = 0.025, p = 0.050, respectively), with no significant difference among PSP, MSA, and PD groups. After adjustment for age, sex, and disease duration, MHR was positively associated with H&Y in the total population (β = 0.288, p < 0.001), negatively associated with MMSE in the PD group (β = −0.245, p = 0.017), and positively associated with both H&Y (β = 0.432, p < 0.001) and UPDRS part II (β = 0.295, p = 0.018) in PPS group. ConclusionNHR and MHR values are not effective as reliable diagnostic markers due to overlap among groups and their limited discriminative capacity in ROC analyses. However, MHR may potentially serve as an indicator reflecting peripheral inflammation in the early stage of PD and PPS compared to HC.

Glymphatic System Assessment Using DTI-ALPS in Age-Dependent Neurodegenerative Diseases

Introduction. Dysfunction of the glymphatic system glymphatic system of the brain is considered a pathogenetic factor in some age-dependent neurodegenerative diseases, including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and normal pressure hydrocephalus (NPH). The innovative method for calculating DTI-ALPS (Diffusion Tensor Image Analysis ALong the Perivascular Space) allows non-invasive assessment of the glymphatic system status using magnetic resonance imaging (MRI). The aim of the study is to compare DTI-ALPS in patients with AD, DLB, PD, and NPH and to evaluate its potential use as a biomarker of the glymphatic system status in these diseases. Materials and methods. The study included 116 subjects: 32 patients with AD, 15 patients with DLB, 31 patients with PD, 11 patients with NPH, and 27 healthy volunteers. Cognitive testing was performed for patients in the main groups using the Montreal Cognitive Assessment (MoCA) score. All subjects underwent diffusion tensor imaging (DTI) of the brain. DTI-ALPS was then calculated. Results. DTI-ALPS index significantly differed across groups (p 0.001). Patients with AD, DLB, and NPH had a significantly lower DTI-ALPS index on both sides compared to the PD group and healthy volunteers (p 0.01). Analysis of the entire sample showed a direct correlation between MoCA score and DTI-ALPS index (p 0.05). Conclusion. This is the first comparison of DTI-ALPS across such a broad range of age-dependent neurodegenerative diseases. Since our DTI-ALPS results were comparable to previously reported data, we believe that this parameter can be used as an indirect marker of the glymphatic system status.

Tailored management of advanced thyroid cancer patients treated with lenvatinib or vandetanib: the role of a multimodal approach.

In differentiated/poorly differentiated (DTC/PDTC) or medullary thyroid cancer (MTC) treated with kinase inhibitors (KIs), additional treatments (ATs) can be performed in selected cases. We retrospectively analysed all the ATs performed in our center in KI-treated TC patients, evaluating the subsequent KI modulation, the local PD in case of loco-regional procedure (LRP) and the AT-related complications. DTC/PDTC patients with or without progressive disease before the first AT (PD and NO PD GROUP, respectively) were analysed separately. In our center, 32 ATs (30 LRPs and 2 radioactive iodine treatments) were performed in 14 DTC/PDTC patients and 4 MTC subjects after the start of systemic therapy with lenvatinib or vandetanib (27 and 5 ATs, respectively). Brain was the most treated site (11/30 LRPs) and external beam radiation was the most employed LRP (18/30 LRPs). KIs dose reduction or discontinuation of KI therapy (at least transient) was performed after 50% of ATs in DTC/PDTC NO PD GROUP. The KI was maintained at the same dosage after 75% and 50% of the ATs performed in DTC/PDTC PD GROUP and MTC, respectively. During the follow-up, local PD was detected after 14 LRPs. Local progression-free survival (LPFS) was significantly shorter in DTC/PDTC PD GROUP in comparison to NO PD GROUP (12 month-LPFS 91.7% versus 15.2%); in patients with MTC, 12 month-LPFS was 50%. AT-related AEs were mostly G1-G2. In selected DTC/PDTC without previous PD and treated with a multimodal strategy, local disease control is generally maintained regardless the KI dose modulation. In DTC/PDTC patients with previous limited PD and in MTC subjects, the choice of performing a LRP and continue the ongoing KI therapy must consider the risk of early local progression. AT-related AEs in KI treated patients were mild in most cases.

Individual-specific metabolic network based on 18F-FDG PET revealing multi-level aberrant metabolisms in Parkinson's disease.

Metabolic network analysis in Parkinson's disease (PD) based on 18F-FDG PET has revealed PD-related metabolic patterns. However, alterations at the systemic metabolic network level and at the connection level between different brain regions still remain unknown. This study aimed to explore metabolic network alterations at multiple network levels among PD patients using an individual-specific metabolic network (ISMN) approach. 18F-FDG-PET images of patients with PD (n = 34) and healthy subjects (n = 47) were collected. Healthy subjects were further separated into reference group (n = 28) and control group (n = 19) randomly. Standardized uptake value normalized by lean body mass ratio (SULr) maps was calculated from the PET images. ISMNs were constructed based on SULr maps for PD patients and controls with reference to the reference group. Comparisons of nodal and edge features were performed between PD and control groups. Correlation analysis was conducted between multilevel network properties and clinical scales in PD group. A linear classifier was trained based on nodal or edge features to distinguish PD from controls. The distance from each patient's ISMN to the group-level difference network showed a negative correlation with Hoehn and Yahr stage (r = -0.390, p = .023). Eight nodes from ISMN were identified which exhibited significantly increased nodal degree in PD patients compared to controls (p < .05). Eleven edges were observed which demonstrated significant distinctions in Z-score values in comparisons to the control group (p < .05). Furthermore, the nodal and edge features showed comparable performances in PD diagnosis compared to the traditional SULr values, with area under the receiver operating characteristic curve larger than 0.91. The proposed ISMN approach revealed systemic metabolic deviations, as well as nodal and edge distinctions in PD, which might be supplementary to the existing findings on PD-related metabolic patterns.

Immune Indicator Changes in Hepatocellular Carcinoma Undergoing TACE Plus ICIs and Anti-VEGF Antibodies/TKIs: A Prognostic Biomarker Analysis.

To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis. This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends. A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5-32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3-CD19+ (p=0.004), CFB (p=0.027), NLR (p<0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8). The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.

Exploratory Analysis of the Association Between Plasma Ceramide Alterations and Cognitive Dysfunction in Parkinson's Disease.

Prior research has underscored the importance of sphingolipid metabolism in Parkinson's disease (PD) pathogenesis. Our objective was to explore the associations between plasma ceramide levels and PD patients with cognitive dysfunction (PD-CD). We enrolled two study populations from Eastern China and the Parkinson's Progression Markers Initiative (PPMI), comprising 290 (100 HCs, 160 PDs, and 30 MSAs) and 429 (125 HCs and 304 PDs) participants, respectively. The plasma levels of ceramides (Cer 16:0, Cer 18:0, Cer 24:0, and Cer 24:1) were tested via HPLC-MS/MS analysis. Compared with those in the HC group, the plasma levels of Cer 18:0, Cer 24:1, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were higher in both the PD and MSA groups. Significant differences in the plasma levels of Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0 were observed among the PD-NC (PD with normal cognition), PD-MCI (PD with mild cognitive impairment), and PDD (PD dementia) groups, with the PDD group exhibiting the highest levels. PD patients with higher baseline levels of plasma ceramides (specifically, Cer 18:0, Cer 16:0/Cer 24:0, Cer 18:0/Cer 24:0, and Cer 24:1/Cer 24:0) demonstrated accelerated cognitive decline compared with individuals who had lower baseline plasma ceramide levels during the 5-year follow-up period. A biomarker panel including Cer 18:0/Cer 24:0 and Cer 24:1/Cer 24:0 could effectively differentiate PD-CD from PD-NC with notable diagnostic accuracy. Our results indicate that plasma ceramide levels could potentially be used as diagnostic biomarkers for PD-CD.