BACKGROUND: Cerebral small vessel disease (SVD) induces vascular cognitive impairment (VCI) such as subcortical vascular dementia (SVaD) and subcortical vascular mild cognitive impairment (svMCI). We compared MRI parameters between SVaD and svMCI and determined which MRI parameters best correlated with cognitive function and disability on cross-sectional and longitudinal analyses within them. METHODS: Twenty-four patients with SVaD and twelve with svMCI were recruited. They underwent multimodal MRIs including fluid-attenuated inversion recovery lesion load, lacunar infarct number, and fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor imaging (DTI), neuropsychological testing, Sum of Boxes of Clinical Dementia Rating Scale (CDR-SB), Barthel Index, and the Korean version of a Geriatric Depression Scale (GDS-K). Seventeen patients were retested after 20 months for a brain MRI and clinical evaluation. RESULTS: There were significant differences in average MD and peak height of MD histograms within normal-appearing brain tissue (NABT) between SVaD and svMCI patients. In the cross-sectional analysis, average MD within NABT significantly correlated with the composite neuropsychology score (r=-0.80, p<0.001), the composite executive function score (r=-0.67, p< 0.001), and the CDR-SB (r=0.54, p=0.001), and the Barthel Index correlated with peak heights of the MD histograms (r=0.37, p=0.03) in NABT. Changes of CDR-SB was associated with changes of average MD within WMH (r=0.57, p=0.02), and changes of GDS-K was associated with changes of WMH volume (r=0.51, p=0.04) on a longitudinal scale. CONCLUSIONS: DTI parameters in NABT correlated with cognitive impairment and disability in VCI associated with SVD. Clinical progression of SVD was associated with some increment of WML volume and ultrastructural changes in WMH.
Anisotropy ; Brain ; Cerebral Small Vessel Diseases ; Cross-Sectional Studies ; Dementia ; Dementia, Vascular ; Depression ; Diffusion ; Diffusion Tensor Imaging ; Executive Function ; Glycosaminoglycans ; Humans ; Mild Cognitive Impairment ; Neuropsychological Tests ; Neuropsychology ; Stroke, Lacunar

Cyclooxygenase-2 (COX-2) has been reported to be associated with tumor development and progression as well as to protect cells from apoptosis induced by various cellular stresses. Through a tetracycline-regulated COX-2 overexpression system, we found that COX-2 inhibits detachment-induced apoptosis (anoikis) in a human bladder cancer cell line, EJ. We also found that the inhibition of anoikis by COX-2 results from activation of the PI-3K/Akt pathway as evidenced by suppression of the COX-2 effect on anoikis by a PI-3K inhibitor, LY294002. Furthermore, COX-2 enhanced Mcl-1 expression in the anoikis process, implying that Mcl-1 also may be involved in mediating the survival function of COX-2. Together, these results suggest that COX-2 inhibits anoikis by activation of the PI-3K/Akt pathway and probably by enhancement of Mcl-1 expression in human bladder cancer cells. This anti- anoikis effect of COX-2 may be a part of mechanisms to promote tumor development and progression.
1-Phosphatidylinositol 3-Kinase/*metabolism ; Anoikis/*physiology ; Bladder Neoplasms/*metabolism/pathology ; Enzyme Activation ; Humans ; Neoplasm Proteins/*metabolism ; Prostaglandin-Endoperoxide Synthase/*metabolism ; Protein-Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Research Support, Non-U.S. Gov't ; Signal Transduction ; Transfection ; Tumor Cells, Cultured

Background: The purpose of this study was to evaluate the effect of concomitant open distal clavicle excision (DCE) on postoperative clinical outcomes and incidence of acromial and scapular stress fractures (ASFs) in patients with symptomatic acromioclavicular joint osteoarthritis (ACJ OA) undergoing reverse total shoulder arthroplasty (RTSA). Methods: A single-surgeon retrospective cohort study was conducted including patients who underwent primary elective RTSA with or without DCE from 2015 to 2019 with a minimum 6-month follow-up period. Shoulder active range of motion (AROM) and visual analog scale (VAS) pain were recorded preoperatively and postoperatively. ASFs and other adverse events were identified using postoperative notes and/or radiographs. Characteristics and outcomes were compared between the RTSA and RTSA-DCE groups. Results: Forty-six RTSA patients (mean age, 67.9±8.7 years; 60.9% male; mean follow-up, 24.9±16.6 months) and 70 RTSA-DCE patients (mean age, 70.2±8.9 years; 20.0% male; mean follow-up, 22.7±12.9 months) were included. There were no significant intergroup differences in rates of ASF (RTSA, 0.0% vs. RTSA-DCE, 1.4%; P=1.00), stress reactions (RTSA, 8.7% vs. RTSA-DCE, 11.4%; P=0.76), reoperation, revision, or infection (all P>0.05), or in pre-to-postoperative reduction in VAS pain (P=0.17) at latest follow-up. However, the RTSA-DCE group had greater pre-to-postoperative improvement in flexion AROM (RTSA, 43.7°±38.5° vs. RTSA-DCE, 59.5°±33.4°; P=0.03) and internal rotation (IR) AROM (P=0.02) at latest follow-up. Conclusions Concomitant DCE in RTSA improves shoulder flexion and IR AROM, alleviates shoulder pain, and does not increase the risk of ASFs.Level of evidence: III.

Purpose: Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed. Materials and Methods: Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety. Results: Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia. Conclusion Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.