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(1) Background: Comprehensive evaluation of guideline-concordant care (GCC) across all PDAC stages has yet to be thoroughly conducted. This study aimed to characterize treatment patterns and assess factors associated with receiving GCC among patients with pancreatic ductal adenocarcinoma (PDAC) in California. (2) Methods: Data on adult patients with PDAC were extracted from the California Cancer Registry (2004–2020). GCC is defined according to the recommendations provided by the National Comprehensive Cancer Network. We used multivariable logistic regression to identify factors associated with receiving GCC. A Cox model was used to examine the association of GCC with overall survival. (3) Results: A total of 50,346 PDAC patients were included (stage 1: 10%; stage 2: 25%; stage 3: 11%; stage 4: 54%). Only 46.7% of all patients received GCC (stage 1: 20%; stage 2: 40%; stage 3: 69%; stage 4: 50%). Only 31% of stage 1 patients underwent surgery. Factors inversely associated with receiving GCC were Hispanic ethnicity (OR 0.78; p < 0.001), Black race (OR 0.74; p < 0.001), having no insurance (OR 0.40; p < 0.001]), and a Charlson–Deyo score of ≥2 (OR 0.68; p < 0.001). Adherence to GCC was associated with improved survival (Hazard Ratio 0.39; p < 0.001). Notably, patients with stage 1 PDAC who received GCC had a median survival of 47 months vs. 8 months for those who did not. (4) Conclusions: Although stage 1 PDAC patients have the greatest potential for survival with GCC, only 20% of patients received such treatment. Thus, it is crucial to identify and address the modifiable factors contributing to these suboptimal care patterns.

Pancreatic neuroendocrine tumors (PNETs) are typically diagnosed using endoscopic ultrasound-guided (EUS) biopsy, which can be associated with complications. Since 2016, DOTATATE PET/CT has emerged as an effective tool to localize and stage PNETs. Patients with PNETs who underwent R0 resections were identified from the 2004–2019 National Cancer Database PUF. Joinpoint regression and multivariable logistic regression were used to analyze trends in the use of biopsy. Of 16,746 R0 resected PNET patients, 44 ​% underwent diagnostic biopsy. Joinpoint regression showed a significant increase in the use of biopsy from 2004 to 2019 (APC 1.80, p ​< ​0.001). A higher percentage of patients diagnosed after DOTATATE approval underwent biopsy compared to those diagnosed before (48 ​% vs. 42 ​%, p ​< ​0.001). Adjusted analysis showed diagnosis after 2016 was associated with increased odds of biopsy (OR ​= ​1.67, p ​< ​0.001). Despite technologic advancement with DOTATATE PET/CT, there has been a significant increase in the proportion of resectable PNETs undergoing preoperative biopsy. •Nearly half of patients with resectable PNET in the USA undergo diagnostic biopsy.•Use of diagnostic biopsy for resectable PNETs has increased between 2004 and 2019.•Diagnosis from 2016 to 2019 is associated with significantly increased odds of biopsy.•Odds of undergoing biopsy differ by geographic region.

Current pharmacological approaches have failed to provide complete remission for patients with Attention-Deficit/Hyperactivity Disorder (ADHD). This study aimed to evaluate the efficacy and tolerability of resveratrol (that have been shown to have antioxidative, anti-inflammatory, and anti-apoptotic effects) as an adjunct to methylphenidate in pharmacologic treatment of ADHD. This 8-week, double-blinded, placebo-controlled trial randomized 66 participants to receive either 500 mg/day resveratrol or matched placebo in addition to methylphenidate. ADHD symptoms were evaluated in the patients using the Parent and Teacher versions of ADHD-Rating Scale (ADHD-RS) at three measurement points with time intervals of 4 weeks. Furthermore, the tolerability of the treatment strategies was systematically compared. Repeated measures analysis demonstrated a significant effect for time–treatment interaction on all three subscales of the Parent ADHD-RS during the trial period (total: p = 0.015; inattention: p = 0.032; hyperactivity/impulsivity: p = 0.036). Nevertheless, the effect for time–treatment interaction was not significant for the Teacher version of ADHD-RS (total: F = 0.81, df = 1.33, p = 0.401; inattention: F = 0.57, df = 1.37, p = 0.507; hyperactivity/impulsivity: F = 0.65, df = 1.34, p = 0.466). The frequencies of complications in the treatment groups were similar. Resveratrol administration for a duration of 8 weeks improved characteristic symptoms in patients with ADHD according to their parents. Further investigations containing larger sample sizes, longer supplementation periods, and dose–response evaluations are required to replicate these findings in ADHD children more confidently.

ObjectivesTo investigate the associations of medial and lateral patellofemoral osteoarthritis (PF-OA) at baseline with symptomatic and radiographic OA outcomes in the medial tibiofemoral compartment (MTFC) over 4 years, according to baseline overweight status.MethodsData and MRI images of 600 subjects in the FNIH-OA biomarkers consortium were used. Symptomatic worsening and radiographic progression of MTFC-OA were defined using Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores and MTFC joint space narrowing (JSN) from baseline to 4-year follow-up. Baseline MRIs were read to establish PF-OA diagnosis. The association between baseline regional PF-OA pattern and odds for MTFC-OA progression was evaluated using regression models (adjusted for relevant confounding covariates including body mass index (BMI), age, sex, PF alignment measurements, KL grade, and knee alignment). To evaluate the effect modifying role for overweight status, stratification analysis was performed (BMI ≥ 25 vs. < 25 kg/m2).ResultsAt baseline, 340 (56.7%), 255 (42.5%), and 199 (33.2%) subjects had OA in the medial, lateral, and both PF compartments. Baseline medial PF-OA was associated with WOMAC pain score and MTFC JSN progression at 4 years (Adjusted OR:1.56[95%CI:1.09–2.23] and 1.59[1.11–2.28], respectively) but not lateral PF-OA. In stratification analysis, overweight status was found to be an effect modifier for medial PF-OA and WOMAC pain (OR in overweight vs. non-overweight subjects:1.65[1.13–2.42] vs. 0.50[0.12–1.82]) as well as MTFC-JSN progression (1.63[1.12–2.4] vs. 0.75[0.19–2.81]).ConclusionsIn addition to the known confounding effect of BMI for PF-OA and MTFC-OA, the overweight status may also play an effect modifier role in the association between baseline medial PF-OA and MTFC-OA progression, which is amenable to secondary prevention.

Behçet's disease (BD) is a chronic multi-systemic vasculitis with a considerable prevalence in Asian countries. There are many genes associated with a higher risk of developing BD, one of which is endoplasmic reticulum aminopeptidase-1 (ERAP1). In this study, we aimed to investigate the interactions of ERAP1 single nucleotide polymorphisms (SNPs) using a novel data mining method called Model-based multifactor dimensionality reduction (MB-MDR). We have included 748 BD patients and 776 healthy controls. A peripheral blood sample was collected, and eleven SNPs were assessed. Furthermore, we have applied the MB-MDR method to evaluate the interactions of ERAP1 gene polymorphisms. The TT genotype of rs1065407 had a synergistic effect on BD susceptibility, considering the significant main effect. In the second order of interactions, CC genotype of rs2287987 and GG genotype of rs1065407 had the most prominent synergistic effect (β = 12.74). The mentioned genotypes also had significant interactions with CC genotype of rs26653 and TT genotype of rs30187 in the third-order (β = 12.74 and β = 12.73, respectively). To the best of our knowledge, this is the first study investigating the interaction of a particular gene's SNPs in BD patients by applying a novel data mining method. However, future studies investigating the interactions of various genes could clarify this issue.

Behçet’s Disease (BD) pathogenesis remains unclear, but some genetic loci and environmental factors are proposed to play a role. Here, we investigate the association of the endoplasmic reticulum aminopeptidase-1 ( ERAP1 ) gene variants and HLA-B*51 with BD susceptibility and clinical manifestations in Iranian patients. In the study, 748 BD patients and 776 healthy individuals were included. The MGB-TaqMan Allelic Discrimination method was used to genotype 10 common missense single nucleotide polymorphisms (SNPs) and one intronic SNP in the ERAP1 gene region. We found no significant association between the 11 SNPs and BD in allelic and genotypic association tests. However, rs30187 showed the strongest association with BD in the recessive genotype model of the risk T allele in HLA-B*51 carriers. Although this became insignificant after correcting for multiple comparisons, the homozygous rs30187 risk allele genotype (TT) increased disease susceptibility in HLA-B*51 carriers in epistasis analysis, and the rs30187 TT recessive genotype showed a significant association with risk of cardiac involvement in the all patients and articular involvements in HLA-B*51 positive patients. Our findings suggest that gene-gene interactions between HLA-B*51 and ERAP1 variants is important for BD development, however, ERAP1 variants which interact with HLA-B*51 may differ among disease phenotypes or populations.

Autonomic dysfunction (AD) is one of the non-motor features of Parkinson's disease (PD). Some symptoms tend to occur in the early stages of PD. AD also has a great impact on patient's quality of life. In this study, we aimed to discover the association between AD (Scales for Outcomes in Parkinson's disease-Autonomic, SCOPA-AUT) and microstructural changes in white matter tracts in drug-naïve early PD patients to elucidate the central effects of autonomic nervous system impairments. In total, this study included 85 subjects with PD recruited from the Parkinson's Progression Markers Initiative (PPMI) database. Among the 85 PD patients, 38 were in Hoehn & Yahr stage 1 (HY1PD) and 47 were in stage 2 (HY2PD). Diffusion magnetic resonance imaging (DMRI) data were reconstructed in the MNI space using q-space diffeomorphic reconstruction to obtain the spin distribution function. The spin distribution function (SDF) values were used in DMRI connectometry analysis. We investigated through diffusion MRI connectometry the structural correlates of white matter tracts with SCOPA-AUT subscores and total score. Connectometry analysis also revealed positive association with white matter density in bilateral corticospinal tract in HY1PD patients and negative association in genu of corpus callosum (CC) and, bilateral cingulum in both groups. In addition, there were associations between gastrointestinal, sexual, thermoregulatory and urinary items and structural brain connectivity in PD. Our study reveals positive correlation, suggesting neural compensations in early PD. Cingulum and CC tracts have well-known roles in PD pathology, compatible with our findings that bring new insights to specific areas of AD and its role in central nervous system (CNS) neurodegeneration, paving the way for using prodromal makers in the diagnosis and treatment of PD.

Purinergic receptors stimulation by adenosine triphosphate (ATP) contributes significantly to macrophage activation, and also macrophage cell death. Upon the macrophage activation, the protein load of the endoplasmic reticulum is increased which is resulted in the activation of unfolded protein response (UPR). In the current study, we aimed to evaluate the connection between prototypic P2X7 receptor agonist, extracellular 2ʹ(3ʹ)-O-(4-Benzoylbenzoyl)-ATP (BzATP), and the UPR pathway in macrophages. The monocyte-derived macrophages from blood samples of 14 healthy volunteers were skewed toward M1 macrophages after incubation with LPS and IFN-γ. M1 macrophages were treated with 200 µM BzATP. The expression levels of UPR genes, including CHOP, HERP, GADD34, XBP1, and ATF6 in macrophages before and after treatment were measured using real-time polymerase chain reaction. The results demonstrated that the expression of CHOP, HERP, and ATF6 is significantly decreased and the expression level of GADD34 and XBP1 is significantly increased after M1 polarization. BzATP not only significantly increased the expression levels of CHOP, GADD34, ATF6, and HERP but also significantly decreases the XBP1 expression level in M1 macrophages. The present study showed that BzATP induces cellular stress in M1 macrophages by elevating the expression levels of UPR genes including CHOP, GADD34, ATF6, and reducing cell viability.