Tag: nevin manimala

CNS Neurosci Ther. 2023 Jun 19. doi: 10.1111/cns.14316. Online ahead of print.

ABSTRACT

BACKGROUND: The systematic molecular associations between the peripheral blood cells and brain in Alzheimer’s disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers.

METHODS: Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD.

RESULTS: By bioinformatics analysis, a total of 243 genes were differentially expressed in the central and peripheral systems, mainly enriched in three modules: immune response, glucose metabolism and lysosome. In addition, lysosome related gene ATP6V1E1 and immune response related genes (IL2RG, OSM, EVI2B TNFRSF1A, CXCR4, STAT5A) were significantly correlated with Aβ or Tau pathology. Finally, receiver operating characteristic (ROC) analysis revealed that ATP6V1E1 showed high-diagnostic potential for AD.

CONCLUSION: Taken together, our data identified the main pathological pathways in AD progression, particularly the systemic dysregulation of the immune response, and provided peripheral biomarkers for AD diagnosis.

PMID:37334737 | DOI:10.1111/cns.14316

Ann Surg. 2023 Jun 19. doi: 10.1097/SLA.0000000000005958. Online ahead of print.

ABSTRACT

OBJECTIVE: We sought to evaluate symptomatic adverse event (AE) rates among patients with pancreatic cancer receiving neoadjuvant therapy on clinical trial (A021501) using the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE).

SUMMARY BACKGROUND DATA: To date, pancreatic cancer clinical trials have measured AEs using standard physician reporting (CTCAE). Patient-reported symptomatic AEs have been incompletely characterized.

METHODS: A021501 (Dec 31, 2016-Jan 1, 2019) randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX + hypofractionated radiotherapy (Arm 2), followed by pancreatectomy and adjuvant FOLFOX6. Patients completed PRO-CTCAE assessments at baseline, on day 1 of each chemotherapy cycle, and daily during radiotherapy.

RESULTS: Of 126 patients, 96 (76%) initiated treatment and completed a baseline plus at least 1 post-baseline PRO-CTCAE assessment. Diarrhea and fatigue were the only symptomatic grade 3 or higher AEs identified in at least 10% of patients using CTCAE. At least 10% of all patients reported an adjusted PRO-CTCAE composite grade 3 AE during neoadjuvant treatment for 10 of 15 items: anxiety (10%), bloating of abdomen (16%), decreased appetite (18%), diarrhea (13%), dry mouth (21%), fatigue (36%), nausea (18%), generalized pain (16%), abdominal pain (21%), and problems tasting (32%). Decreased appetite was higher in Arm 2 than in Arm 1 (P=0.0497); no other differences between study arms were observed.

CONCLUSIONS: Symptomatic AEs during neoadjuvant therapy were common and were reported more frequently by patients using PRO-CTCAE than were recorded by clinicians using standard CTCAE.

PMID:37334719 | DOI:10.1097/SLA.0000000000005958

Teach Learn Med. 2023 Jun 19:1-8. doi: 10.1080/10401334.2023.2224789. Online ahead of print.

ABSTRACT

Phenomenon: Existing literature, as well as anecdotal evidence, suggests that tiered clinical grading systems may display systematic demographic biases. This study aimed to investigate these potential inequities in-depth. Specifically, this study attempted to address the following gaps in the literature: (1) studying grades actually assigned to students (as opposed to self-reported ones), (2) using longitudinal data over an 8-year period, providing stability of data, (3) analyzing three important, potentially confounding covariates, (4) using a comprehensive multivariate statistical design, and (5) investigating not just the main effects of gender and race, but also their potential interaction. Approach: Participants included 1,905 graduates (985 women, 51.7%) who received the Doctor of Medicine degree between 2014 and 2021. Most of the participants were white (n = 1,310, 68.8%) and about one-fifth were nonwhite (n = 397, 20.8%). There were no reported race data for 10.4% (n = 198). To explore potential differential grading, a two-way multivariate analysis of covariance was employed to examine the impact of race and gender on grades in eight required clerkships, adjusting for prior academic performance. Findings: There were two significant main effects, race and gender, but no interaction effect between gender and race. Women received higher grades on average on all eight clerkships, and white students received higher grades on average on four of the eight clerkships (Medicine, Pediatrics, Surgery, Obstetrics/Gynecology). These relationships held even when accounting for prior performance covariates. Insights: These findings provide additional evidence that tiered grading systems may be subject to systematic demographic biases. It is difficult to tease apart the contributions of various factors to the observed differences in gender and race on clerkship grades, and the interactions that produce these biases may be quite complex. The simplest solution to cut through the tangled web of grading biases may be to move away from a tiered grading system altogether.

PMID:37334710 | DOI:10.1080/10401334.2023.2224789

J Biomol Struct Dyn. 2023 Jun 19:1-13. doi: 10.1080/07391102.2023.2225007. Online ahead of print.

ABSTRACT

The in silico evaluation of 27 p-aminosalicylic acid derivatives, also referred to as neuraminidase inhibitors was the focus of the current study. To search and predict new potential neuraminidase inhibitors, this study was based on the ligand-based pharmacophore modeling, 3D QSAR, molecular docking, ADMET and MD simulation studies. The data was generated from recently reported inhibitors and divided into two groups, one of these group has 17 compounds for training and the second group has 10 compounds for testing purpose. The generated pharmacophore has known as ADDPR_4 was found statistically significant 3D-QSAR model owing the high trust scores (R² = 0.974, Q² = 0.905, RMSE = 0.23). Morever external validation was also employed to evaluate the prediction capacity of the built pharmacophore model (R²_pred = 0.905). In addition, in silico ADMET, analyses were employed to evaluate the obtained hits for drug likeness properties. The stability of formed complexes was further evaluated using molecular dynamics. Top two hits showed stable complexes with Neuraminidase based on calculated total binding energy by MM-PBSA.Communicated by Ramaswamy H. Sarma.

PMID:37334701 | DOI:10.1080/07391102.2023.2225007

Ann Surg. 2023 Jun 19. doi: 10.1097/SLA.0000000000005942. Online ahead of print.

ABSTRACT

OBJECTIVE: This proof-of-concept explores the use of an episode grouper to more accurately identify the complete set of surgical services typically provided in a surgical episode of care and the corresponding range of prices, using colectomy for cancer as the example.

SUMMARY /BACKGROUND DATA: Price transparency is an important policy issue that will require surgeons to better understand the components and cost of care.

METHODS: This study uses the Episode Grouper for Medicare (EGM) business logic to construct colectomy surgical episodes of care for cancer using Medicare claims data for the Boston Hospital Referral Region (HRR) from 2012-2015. Descriptive statistics show the mean reimbursement based on patient severity and stage of surgery along with the number of unique clinicians billing for care and the mix of services provided.

RESULTS: The EGM episode grouper identified 3,182 colectomies in Boston between 2012 and 2015 with 1,607 done for cancer. The mean Medicare allowed amount per case is $29,954 and varies from $26,605 to $36,850 as you move from low to high severity cases. The intra-facility stage is the most expensive ($23,175 on average) compared to the pre ($780) and post ($6,479) facility stages. There is tremendous heterogeneity in service mix.

CONCLUSION: Episode groupers are a potentially valuable tool for identifying variation in service mix and teaming patterns that correlate with total price. By looking at patient care holistically, stakeholders can identify opportunities for price transparency and care redesign that have heretofore been hidden.

PMID:37334700 | DOI:10.1097/SLA.0000000000005942

Pigment Cell Melanoma Res. 2023 Jun 19. doi: 10.1111/pcmr.13103. Online ahead of print.

ABSTRACT

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

PMID:37334675 | DOI:10.1111/pcmr.13103

J Neuromuscul Dis. 2023 Jun 12. doi: 10.3233/JND-230025. Online ahead of print.

ABSTRACT

Open bite (OB) is a common malocclusion in individuals with orofacial dysfunction and syndromes, especially in neuromuscular diseases.

OBJECTIVES: The objectives were to explore the prevalence of OB in myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and to create and compare orofacial dysfunction profiles.

METHODS: In this database study, 143 individuals with DM1 and 99 with DMD were included. The Mun-H-Center questionnaire and observation chart were used together with the Nordic Orofacial Test -Screening (NOT-S) to create orofacial dysfunction profiles. OB was categorised as: lateral (LOB); anterior (AOB); severe anterior (AOBS); or both types of anterior OB (AOBTot). Descriptive and multivariate statistics were used to compare the OB prevalence and to study associations with orofacial variables, respectively.

RESULTS: There was a statistically significant difference in OB prevalence between the DM1 (37%) and DMD (49%) groups (p = 0.048). LOB was seen in < 1% of DM1 and 18% of DMD. LOB was associated with macroglossia and closed mouth posture, AOB with hypotonic lips, and open mouth posture and AOBS with hypotonic jaw muscles. The orofacial dysfunction profiles showed similar patterns, although the mean NOT-S total scores for DM1 and DMD were 4.2±2.8 (median 4.0, min-max 1-8) and 2.3±2.0 (median 2.0, min-max 0-8), respectively.

LIMITATIONS: The two groups were not age- or gender-matched.

CONCLUSION: OB malocclusion is common in patients with DM1 and DMD and is associated with different types of orofacial dysfunction. This study highlights the need for multi-disciplinary assessments to support tailored treatment strategies that improve or sustain orofacial functions.

PMID:37334614 | DOI:10.3233/JND-230025

J Alzheimers Dis. 2023 Jun 10. doi: 10.3233/JAD-221116. Online ahead of print.

ABSTRACT

BACKGROUND: Herpesviruses have been proposed to be involved in Alzheimer’s disease development as potentially modifiable pathology triggers.

OBJECTIVE: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE ɛ4.

METHODS: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).

RESULTS: Anti- HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti- CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti- CMV IgG carriers. Anti- HSV-1 IgG interacted with APOE ɛ4 in association with worse TMT-A and better enhanced cued recall. Anti- HSV IgM interacted with APOE ɛ4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.

CONCLUSION: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.

PMID:37334589 | DOI:10.3233/JAD-221116

Rev Esp Salud Publica. 2023 Jun 19;97:e202306052.

ABSTRACT

OBJECTIVE: HIV Clinical Guidelines have positioned integrase inhibitors recently as first-line treatment. However, two of these drugs have also been associated with adverse side effects on the central nervous system, especially with sleep disturbances. The objective was to analyse the influence of bictegravir and dolutegravir on the sleep quality in HIV patients.

METHODS: An observational, cross-sectional study was carried out between December 2020 and January 2021 in HIV patients attended in a pharmacy care clinic. Demographic and adherence variables were collected. Sleep quality was measured using the Pittsburgh questionnaire or PSQI. We classified patients into two groups: patients with bictegravir or dolutegravir in their treatment (study group) and the rest (control group). The influence of the variables collected on the PSQI result was analysed using the Chi-Square test for categorical variables and the student t-test or Mann-Whitney U test for continuous variables.

RESULTS: One hundred and nineteen patients were included. 64% in the study group and 67% in the control group suffered from sleep disorders according to the PSQI questionnaire (p=0.788). Neither were statistical differences found when the different components of sleep were analysed between the two groups.

CONCLUSIONS: A high percentage of patients, regardless of whether their treatment includes bictegravir or dolutegravir, have problems with their sleep quality. We didn’t find a correlation between sleep quality and treatment with bictegravir or dolutegravir compared to the other treatments.

PMID:37334559

Nucl Med Commun. 2023 Jun 12. doi: 10.1097/MNM.0000000000001719. Online ahead of print.

ABSTRACT

OBJECTIVE: In this study, we aimed to compare the diagnostic value of [68Ga]Ga-Pentixafor and [18F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients.

METHODS: Patients with pathology-proven NSCLC were prospectively included. Patients underwent [18F]FDG and [68Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P-value <0.05 was considered significant.

RESULTS: Twelve consecutive NSCLC patients (mean age: 60 ± 7) were included. All patients underwent both [18F]FDG and [68Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [18F]FDG and [68Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [68Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [18F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [18F]FDG PET/CT (P-values <0.05). Regarding the advantages, [68Ga]Ga-Pentixafor depicted two brain metastases that were missed by [18F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [18F]FDG PET/CT scan was correctly classified as benign by subsequent [68Ga]Ga-Pentixafor PET/CT.

CONCLUSION: [68Ga]Ga-Pentixafor PET/CT was concordant with [18F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [18F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [18F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.

PMID:37334548 | DOI:10.1097/MNM.0000000000001719