Tag: pubmed

Neurol Ther. 2024 Jan 5. doi: 10.1007/s40120-023-00571-9. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study is to develop a clinical tool for the evaluation and follow-up of adolescent and adult patients with 5q spinal muscular atrophy (SMA) and to design its validation.

METHODS: This prospective, non-interventional study will be carried out at five centres in Spain and will include patients aged 16 years or older with a confirmed diagnosis of 5q SMA (biallelic mutation of the survival motor neuron 1 [SMN1] gene). A panel of experts made up of neurologists, physiatrists and Spanish patients’ association (FundAME), participated in the design of the clinical tool. Physicians will administer the tool at three time points (baseline, 12 months and 24 months). Additionally, data from other questionnaires and scales will be collected. Once recruitment is achieved, an interim statistical analysis will be performed to assess its psychometric properties by applying Rasch analysis and classical statistical tests.

RESULTS: The tool will consist of up to 53 items to assess functional status from a clinical perspective in seven key dimensions (bulbar, respiratory, axial, lower, upper, fatigability and other symptoms), which will be collected together with objective clinical measures (body mass index, forced vital capacity, pinch strength and 6-minute walk test).

CONCLUSIONS: The validation of this tool will facilitate the clinical evaluation of adult and adolescent patients with SMA and the quantification of their response to new treatments in both clinical practice and research.

PMID:38180726 | DOI:10.1007/s40120-023-00571-9

Pain Ther. 2024 Jan 5. doi: 10.1007/s40122-023-00570-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic low back pain (cLBP) is a problem globally, creating a tremendous economic burden. Since conventional treatments often fail, various forms of electrical stimulation have been proposed to improve function and decrease pain. Patient-reported outcome measures (PROMs) have not been adequately reported in the electrical stimulation literature.

METHODS: A retrospective independent statistical analysis was conducted on PROMs data for users of H-Wave^® device stimulation (HWDS) collected by the device manufacturer over a period of 4 years. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with “all diagnoses”; this number was then reduced to 2711 patients with nonspecific cLBP, sprain, or strain.

RESULTS: Reported pain was reduced by 3.12 points (0-10 pain scale), with significant (≥ 20%) relief in 85.28%. Function/activities of daily living (ADL) improved in 96.36%, while improved work performance was reported in 81.61%. Medication use decreased or stopped in 64.41% and sleep improved in 59.76%. Over 96% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive associations with longer duration of device use, home exercise participation, and working, whereas older age and longer pain chronicity resulted in reduced benefit. Similar analysis of the larger all-diagnoses cohort demonstrated near-equivalent positive outcomes.

CONCLUSION: Treatment outcomes directly reported by cLBP HWDS patients demonstrated profound positive effects on function and ADL, robust improvement in pain perception, and additional benefits like decreased medication use, better sleep, and improved work performance, representing compelling new evidence of treatment efficacy.

PMID:38180725 | DOI:10.1007/s40122-023-00570-6

Gen Thorac Cardiovasc Surg. 2024 Jan 5. doi: 10.1007/s11748-023-01990-z. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the influence of prolonged cardiopulmonary resuscitation (CPR) on outcomes in heart transplantation with higher risk donor hearts (HRDHs).

METHODS: Patients transplanted in our hospital between May 2006 and December 2019 were divided into 2 groups, HRDH recipients and non HRDH recipients. HRDH was defined as meeting at least one of the following criteria: (1) donor left ventricular ejection fraction ≤ 50%, (2) donor-recipient predicted heart mass ratio < 0.8 or > 1.2, (3) donor age ≥ 55 years, (4) ischemic time > 4 h and (5) catecholamine index > 20. Recipients of HRDHs were divided into 3 groups according to the time of CPR (Group1: non-CPR, Group 2: less than 30 min-CPR, and Group 3: longer than 30 min CPR).

RESULTS: A total of 125 recipients were enrolled in this study, composing of HRDH recipients (n = 97, 78%) and non HRDH recipients (n = 28, 22%). Overall survival and the rate of freedom from cardiac events at 10 years after heart transplantation were comparable between two groups. Of 97 HRDH recipients, 54 (56%) without CPR, 22 (23%) with CPR < 30 min, and 21 (22%) with CPR ≥ 30 min were identified. One-year survival rates were not significantly different among three groups. The 1-year rate of freedom from cardiac events was not also statistically different, excluding the patients with coronary artery disease found in early postoperative period, which was thought to be donor-transmitted disease. Multivariate logistics regression for cardiac events identified that the CPR duration was not a risk factor even in HRDH-recipients.

CONCLUSION: The CPR duration did not affect the outcomes after heart transplantation in HRDH recipients.

PMID:38180694 | DOI:10.1007/s11748-023-01990-z

Inflammopharmacology. 2024 Jan 5. doi: 10.1007/s10787-023-01404-9. Online ahead of print.

ABSTRACT

Depression is linked with oxidative stress and inflammation, where key players include nitric oxide (NO), nuclear factor erythroid 2-related factor 2 (Nrf2), Brain-Derived Neurotrophic Factor (BDNF), and Heme Oxidase-1 (HO-1). Augmenting the efficacy of antidepressants represents a compelling avenue of exploration. We explored the potential of vitamins C and D as adjuncts to escitalopram (Esc) in a lipopolysaccharide (LPS)-induced depression model focusing on the aforementioned biomarkers. Male Swiss albino mice were stratified into distinct groups: control, LPS, LPS + Esc, LPS + Esc + Vit C, LPS + Esc + Vit D, and LPS + Esc + Vit C + Vit D. After a 7-day treatment period, a single LPS dose (2 mg/kg), was administered, followed by comprehensive assessments of behavior and biochemical parameters. Notably, a statistically significant (p < 0.05) alleviation of depressive symptoms was discerned in the Esc + Vit C + Vit D group versus the LPS group, albeit with concomitant pronounced sedation evident in all LPS-treated groups (p < 0.05). Within the cortex, LPS reduced (p < 0.05) the expression levels of NO_x, Nrf2, BDNF, and HO-1, with only HO-1 being reinstated to baseline in the LPS + Esc + Vit D and the LPS + Esc + Vit C + Vit D groups. Conversely, the hippocampal NO_x, Nrf2, and HO-1 levels remained unaltered following LPS administration. Notably, the combination of Esc, Vit C, and Vit D effectively restored hippocampal BDNF levels, which had been diminished by Esc alone. In conclusion, vitamins C and D enhance the therapeutic effects of escitalopram through a mechanism independent of Nrf2. These findings underscore the imperative need for in-depth investigations.

PMID:38180676 | DOI:10.1007/s10787-023-01404-9

Metabolomics. 2024 Jan 5;20(1):13. doi: 10.1007/s11306-023-02081-z.

ABSTRACT

INTRODUCTION: The burden of stroke in patients with hypertension is very high, and its prediction is critical.

OBJECTIVES: We aimed to use plasma lipidomics profiling to identify lipid biomarkers for predicting incident stroke in patients with hypertension.

METHODS: This was a nested case-control study. Baseline plasma samples were collected from 30 hypertensive patients with newly developed stroke, 30 matched patients with hypertension, 30 matched patients at high risk of stroke, and 30 matched healthy controls. Lipidomics analysis was performed by ultrahigh-performance liquid chromatography-tandem mass spectrometry, and differential lipid metabolites were screened using multivariate and univariate statistical methods. Machine learning methods (least absolute shrinkage and selection operator, random forest) were used to identify candidate biomarkers for predicting stroke in patients with hypertension.

RESULTS: Co-expression network analysis revealed that the key molecular alterations of the lipid network in stroke implicate glycerophospholipid metabolism and choline metabolism. Six lipid metabolites were identified as candidate biomarkers by multivariate statistical and machine learning methods, namely phosphatidyl choline(40:3p)(rep), cholesteryl ester(20:5), monoglyceride(29:5), triglyceride(18:0p/18:1/18:1), triglyceride(18:1/18:2/21:0) and coenzyme(q9). The combination of these six lipid biomarkers exhibited good diagnostic and predictive ability, as it could indicate a risk of stroke at an early stage in patients with hypertension (area under the curve = 0.870; 95% confidence interval: 0.783-0.957).

CONCLUSIONS: We determined lipidomic signatures associated with future stroke development and identified new lipid biomarkers for predicting stroke in patients with hypertension. The biomarkers have translational potential and thus may serve as blood-based biomarkers for predicting hypertensive stroke.

PMID:38180633 | DOI:10.1007/s11306-023-02081-z

Int J Comput Assist Radiol Surg. 2024 Jan 5. doi: 10.1007/s11548-023-03044-4. Online ahead of print.

ABSTRACT

PURPOSE: Standardized uptake values (SUVs) derived from ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography are a crucial parameter for identifying tumors or abnormalities in an organ. Moreover, exploring ways to improve the identification of tumors or abnormalities using a statistical measurement tool is important in clinical research. Therefore, we developed a fully automatic method to create a personally normalized Z-score map of the liver SUV.

METHODS: The normalized Z-score map for each patient was created using the SUV mean and standard deviation estimated from blood-test-derived variables, such as alanine aminotransferase and aspartate aminotransferase, as well as other demographic information. This was performed using the least absolute shrinkage and selection operator (LASSO)-based estimation formula. We also used receiver operating characteristic (ROC) to analyze the results of people with and without hepatic tumors and compared them to the ROC curve of normal SUV.

RESULTS: A total of 7757 people were selected for this study. Of these, 7744 were healthy, while 13 had abnormalities. The area under the ROC curve results indicated that the anomaly detection approach (0.91) outperformed only the maximum SUV (0.89). To build the LASSO regression, sets of covariates, including sex, weight, body mass index, blood glucose level, triglyceride, total cholesterol, γ-glutamyl transpeptidase, total protein, creatinine, insulin, albumin, and cholinesterase, were used to determine the SUV mean, whereas weight was used to determine the SUV standard deviation.

CONCLUSION: The Z-score normalizes the mean and standard deviation. It is effective in ROC curve analysis and increases the clarity of the abnormality. This normalization is a key technique for effective measurement of maximum glucose consumption by tumors in the liver.

PMID:38180621 | DOI:10.1007/s11548-023-03044-4

Metabolomics. 2024 Jan 5;20(1):12. doi: 10.1007/s11306-023-02078-8.

ABSTRACT

INTRODUCTION: Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity.

OBJECTIVES: Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood.

METHODS: In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA).

RESULTS: The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59-0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau.

CONCLUSIONS: Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.

PMID:38180611 | DOI:10.1007/s11306-023-02078-8

Eur Arch Otorhinolaryngol. 2024 Jan 5. doi: 10.1007/s00405-023-08432-9. Online ahead of print.

ABSTRACT

PURPOSE: Treatment de-intensification for p16 + oropharyngeal squamous cell carcinoma (OPSCC) is an area of active research to reduce the side effects and improve patients’ quality of life (QoL). In this paper we evaluated the Overall Survival (OS), the Disease-Free Survival (DFS) and the QoL of patients affected by p16 + OPSCC according to their prognostic stage group (PSG) and different treatments.

METHODS: Patients were selected retrospectively through our Electronic Tumor Board Database according to prespecified inclusion criteria. Basic data of eligible patients were recorded and analyzed. Then, OS and DFS were evaluated according to the PSG and the treatments performed. Patients alive completed three questionnaires: the QoL Questionnaire Core 30 (QLQ-C30), the QoL Questionnaire Head & Neck 43 (QLQ-HN43) and the MD Anderson Dysphagia Inventory (MDADI) questionnaire.

RESULTS: Sixty-one patients were included in this study. Eight patients died from the disease and the remaining 53 patients completed the 3 questionnaires. Fifteen (25%) patients were treated with upfront surgery, 6 (10%) patients with definitive radiotherapy and 40 (65%) patients with concomitant chemoradiotherapy. Comparing the DFS and the OS of PSG I patients by the different treatments performed, no statistically significant difference was identified. Patients treated with upfront surgery showed better outcomes in some aspects of their QoL.

CONCLUSION: For p16 + OPSCC PSG I patients, upfront surgery can be considered a valid alternative to radiotherapy or chemoradiotherapy while maintaining a comparable DFS and OS and giving patients better results in terms of specific aspects of their QoL.

PMID:38180604 | DOI:10.1007/s00405-023-08432-9

Birth Defects Res. 2024 Jan 5. doi: 10.1002/bdr2.2295. Online ahead of print.

ABSTRACT

BACKGROUND: Orofacial clefts (OFCs) include cleft palate (CP), cleft lip (CL), and cleft lip with cleft palate (CLP) and require multidisciplinary healthcare services. Alberta, Canada has a publicly funded, universal access healthcare system. This study determined publicly funded healthcare costs for children with an OFC and compared these costs to children without congenital anomalies.

METHODS: This retrospective population-based cohort analysis used the Alberta Congenital Anomalies Surveillance System to identify children born between 2002 and 2018 with an isolated OFC. They were matched 1:1 to a reference cohort based on sex and year of birth. The study population included 1614 children, from birth to 17 years of age linked to administrative databases to estimate annual inpatient and outpatient costs. Average annual all-cause costs were compared using two-sample independent t tests.

RESULTS: The mean total cleft-related costs per patient were highest for children with CLP ($74,138 CAD, standard deviation (SD) $43,447 CAD), followed by CP ($53,062 CAD, SD $74,366 CAD), and CL ($35,288 CAD, SD $49,720 CAD). The mean total all-cause costs per child were statistically significantly higher (p < .001) in children with an OFC ($56,305 CAD, SD $57,744 CAD) compared to children without a congenital anomaly ($18,600 CAD, SD $61,300 CAD).

CONCLUSIONS: Despite public health strategies to mitigate risk factors, the trend for OFCs has remained stable in Alberta, Canada for over 20 years. The costs reported are useful to other jurisdictions for comparison, and to families, healthcare professionals, service planners, and policy makers.

PMID:38179866 | DOI:10.1002/bdr2.2295

J Magn Reson Imaging. 2024 Jan 5. doi: 10.1002/jmri.29217. Online ahead of print.

ABSTRACT

BACKGROUND: Changes in cerebral hemodynamics with aging are important for understanding age-related variation in neuronal health. While many prior studies have focused on gray matter, less is known regarding white matter due in part to measurement challenges related to the lower vascular density in white matter.

PURPOSE: To investigate the impact of age and sex on white matter hemodynamics in a Human Connectome Project in Aging (HCP-A) cohort using tract-based spatial statistics (TBSS).

STUDY TYPE: Retrospective cross-sectional.

POPULATION: Six hundred seventy-eight typically aging individuals (381 female), aged 36-100 years.

FIELD STRENGTH/SEQUENCE: Multi-delay pseudo-continuous arterial spin labeling (ASL) and diffusion-weighted pulsed-gradient spin-echo echo planar imaging sequences at 3.0 T.

ASSESSMENT: A skeleton of mean fractional anisotropy (FA) was produced using TBSS. This skeleton was used to project ASL-derived cerebral blood flow (CBF) and arterial transit time (ATT) measures onto white matter tracts.

STATISTICAL TESTS: General linear models were applied to white matter FA, CBF, and ATT maps, while covarying for age and sex. Threshold-free cluster enhancement multiple comparisons correction was performed for the effects of age and sex, thresholded at P_FWE < 0.05. CBF, ATT, and FA were compared between sex for each tract using analysis of covariance, with multiple comparisons correction for the number of tracts at P_FDR < 0.05.

RESULTS: Significantly lower white matter CBF and significantly prolonged white matter ATTs were associated with older age. These effects were widespread across tracts for ATT. Significant (P_FDR < 0.05) sex differences in ATT were observed across all tracts, and significant sex differences in CBF were observed in all tracts except the bilateral uncinate fasciculus. Females demonstrated significantly higher CBF compared to males across the lifespan. Few tracts demonstrated significant sex differences in FA.

DATA CONCLUSION: This study identified significant sex- and age-associated differences in white matter hemodynamics across tracts.

EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

PMID:38179863 | DOI:10.1002/jmri.29217