Lower serum ferritin levels are associated with worse cognitive performance in aging.

OBJECTIVES: Iron is important for neurogenesis, synaptic development, and neurotransmitter synthesis. Serum ferritin (SF) is a reliable marker for assessing iron stores. Therefore, we evaluated the cognitive function associated with SF levels. We also assessed brain iron content using R2* Magnetic Resonance Imaging (MRI) and its association with SF levels. DESIGN: Data from three cross-sectional observational studies were used. Aging Imageomics (n = 1030) was conducted on aged subjects. Health Imageomics (n = 971) and IR0NMET (n = 175) were conducted in middle-aged subjects. SETTING AND PARTICIPANTS: Participants were enrolled at Dr. Josep Trueta University Hospital facilities. The three cohorts included a total of 2176 subjects (mean age, 52 years; 48% men). MEASUREMENTS: SF levels were measured by standard laboratory methods. Total Digits Span (TDS), and Phonemic Verbal Fluency (PVF) were used to assess executive function. Language function was assessed by semantic verbal fluency (SVF), attention by the Symbol Digit Modalities Test, and memory by the Memory Binding Tests - Total Free Recall and Total Delayed Free Recall. MRI was used to assess the iron content of the brain by R2*. RESULTS: In subjects aged 65 years or older, SF levels were associated with increased TDS (ß = 0.003, p = 0.02), PVF (ß = 0.004, p = 0.01), and SVF (ß = 0.004, p = 0.002) scores. After stratification by sex, these findings were significant only in men, where SF was associated with increased TDS (ß = 0.003, p = 0.01), PVF (ß = 0.004, p = 0.03), and SVF (ß = 0.004, p = 0.009) scores. In middle-aged subjects, SF was also associated with increased SVF scores (ß = 0.005, p = 0.011). Lastly, in men, SF levels were negatively associated with R2*, a surrogate marker of brain iron content, in both the left frontal inferior opercular area (r = -0.41, p = 0.005) and the right frontal inferior opercular area (r = -0.44, p = 0.002). CONCLUSIONS: SF is significantly and positively associated with cognition. In older people with low SF levels, iron supplementation may be a promising therapy to improve cognition.

In silico and in vitro elastase inhibition assessment assays of rosmarinic acid natural product from Rosmarinus officinalis Linn.

The use of various herbs and their compounds has been a strategy widely used in the fight against various human diseases. For example, rosmarinic acid, a bioactive phenolic compound commonly found in Rosemary plants (Rosmarinus officinalis Labiatae), has multiple therapeutic benefits in different diseases, such as cancer. Therefore, the study aimed to evaluate in silico and in vitro the inhibition potential of the enzyme Elastase from the porcine pancreas by rosmarinic acid isolated from the plant species R. officinalis Linn. Through Molecular Docking, the mechanism of action was investigated. In addition, rosmarinic acid presented a range of 5-60 µg/mL and significantly inhibited Elastase. At 60 µg/mL, there was an inhibition of 55% on the enzymatic activity. The results demonstrate the inhibition of Elastase by rosmarinic acid, which can lead to the development of new enzyme inhibitors that can be an inspiration for developing various drugs, including anticancer drugs.

Utility of expanded anterior column resection versus decompression-alone for local control in the management of carcinomatous vertebral column metastases undergoing adjuvant stereotactic radiotherapy.

BACKGROUND CONTEXT: With improvements in adjuvant radiotherapy and minimally invasive surgical techniques, separation surgery has become the default surgical intervention for spine metastases at many centers. However, it is unclear if there is clinical benefit from anterior column resection in addition to simple epidural debulking prior to stereotactic body radiotherapy (SBRT). PURPOSE: To examine the effect of anterior column debulking versus epidural disease resection alone in the local control of metastases to the bony spine. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Ninety-seven patients who underwent open surgery followed by SBRT for spinal metastases at a single comprehensive cancer center. OUTCOME MEASURES: Local tumor recurrence following surgery and SBRT. METHODS: Data were collected regarding radiation dose, cancer histology, extent of anterior column resection, and recurrence. Tumor involvement was categorized using the International Spine Radiosurgery Consortium guidelines. Univariable analyses were conducted to determine predictors of local recurrence and time to local recurrence. RESULTS: Among the 97 included patients, mean age was 60.5±11.4 years and 51% of patients were male. The most common primary tumor types were lung (20.6%), breast (17.5%), kidney (13.4%) and prostate (12.4%). Recurrence was seen in 17 patients (17.5%) and local control rates were: 85.5% (1-year), 81.1% (2-year), and 54.9% (5-year). Overall predictors of local recurrence were tumor pathology (p<.01; renal cell carcinoma and colorectal adenocarcinoma associated with poorest PFS) and undergoing anterior column debulking versus epidural decompression-alone (p=.03). Only tumor pathology predicted time to local recurrence (p<.01), though inspection of Kaplan-Meier functions showed superior long-term local control in patients with radiosensitive tumor pathologies, no previous irradiation of the metastasis, and who underwent anterior column resection versus epidural removal alone. Median time to recurrence was 288 days with 100% of lesions showing anterior column recurrence and recurrence in the epidural space. CONCLUSIONS: With the increasing shift towards surgery as a neoadjuvant to radiotherapy for patients with spinal column metastases, the role for surgical debulking has become less clear. In the present study, we find that anterior column debulking as opposed to epidural debulking-alone decreases the odds of local recurrence and improves long-term local control.

Drivers of Readmission and Reoperation After Surgery for Vertebral Column Metastases.

OBJECTIVE: To determine those clinical, demographic, and operative factors that predict 30-day unplanned reoperation and readmission within a population of adults who underwent spinal metastasis surgery at a comprehensive cancer center. METHODS: Adults who underwent spinal metastasis surgery at a comprehensive cancer center were analyzed. Data included baseline laboratory values, cancer history, demographics, operative characteristics and medical comorbidities. Medical comorbidities were quantified using the modified Charlson Comorbidity Index (CCI). Values associated with the outcomes of interest were then subjected to multivariable logistic regression to identify independent predictors of readmission and reoperation. RESULTS: A total of 345 cases were identified. Mean age was 59.4 ± 11.7 years, 56% were male, and the racial makeup was 64% white, 29% black, and 7.3% other. Forty-two patients (12.2%) had unplanned readmissions, most commonly for wound infection with dehiscence (14.2%), venous thromboembolism (14.2%), and bowel obstruction/complication (11.9%). Thirteen patients required reoperation (4%), most commonly for wound infection with dehiscence (39%) or local recurrence (23%). Multivariable analysis showed that the modified CCI (odds ratio [OR], 1.25; 95% confidence interval [CI] 1.03-1.52; P = 0.03) was an independent predictor of 30-day readmission. Independent predictors of 30-day unplanned reoperation were: black (vs. white) race (OR, 0.08; 95% CI, 0.01-0.41; P < 0.01), length of stay (OR, 1.05 per day; 95% CI, 1.00-1.09; P = 0.04), and CCI (OR, 1.72 per point; 95% CI, 1.29-2.28; P < 0.01). CONCLUSIONS: Increasing medical comorbidities is independently predictive of both 30-day unplanned readmission and reoperation after spinal metastasis surgery. Unplanned reoperation is also positively predicted by a longer index admission. Neither tumor pathology nor age predicted outcome, suggesting that poor wound-healing factors and increased surgical morbidity may best predict these adverse outcomes.

Vitamin B12 supplementation orally and intramuscularly in people with obesity undergoing gastric bypass.

PURPOSE: Although bariatric surgery can facilitate weight loss and improve many diseases, it impairs the absorption of many vitamins and micronutrients. Vitamin B12 is important for these patients and should be controlled and supplemented postoperatively. The aim of this paper is to compare serum vitamin B12 levels in two forms of supplementation (oral vs. intramuscular) for 6 months after gastric bypass. METHODS: In a prospective controlled cohort study, people with obesity patients undergoing gastric bypass received vitamin B12 supplementation either orally or intramuscularly. The patients were followed for 6 months, receiving serial doses of vitamin B12 and methylmalonic acid assessment at 6 months. RESULTS: A total of 53 patients were divided into two homogeneous groups: an oral group (n=24) and an intramuscular group (n=29). Serum vitamin B12 was measured preoperatively and postoperatively at 1, 2, 3, and 6 months. Serum methylmalonic acid was measured at 6 months. At each point, the serum vitamin B12 level remained within reference values in both groups, although it was higher in the oral group (p<0.001). Methylmalonic acid also remained within reference values in both groups, with no significant differences. CONCLUSION: Despite the anatomical and functional alterations that impair vitamin B12 absorption after gastric bypass, oral vitamin B12 supplementation was as effective as intramuscular in this population.

Biomechanical evaluation comparing zero-profile devices versus fixed profile systems in a cervical hybrid decompression model: a biomechanical in vitro study.

BACKGROUND CONTEXT: The use of zero-profile devices and the need for posterior fixation in conjunction with a cervical hybrid decompression model have yet to be investigated. PURPOSE: To compare the biomechanics of zero-profile and fixed profile cervical hybrid constructs composed of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF). Fixed profile devices included anterior plating, whereas zero-profile devices included integrated screws. STUDY DESIGN: In vitro cadaveric biomechanical study. METHODS: Twelve fresh-frozen cadaveric spines (C2-C7) were divided into two groups of equal bone mineral density, fixed profile versus zero profile (n=6). Groups were instrumented from C3-C6 with either (1) an expandable ACCF device and a static ACDF spacer with an anterior plate (Hybrid-AP) or (2) a zero-profile ACCF spacer with adjacent zero-profile ACDF spacer (Hybrid-Z). Motion was captured for the (1) intact condition, (2) a hybrid model with lateral mass screws (LMS), (3) a hybrid model without LMS, and (4) a hybrid model without LMS following simulated repetitive loading (fatigue). RESULTS: Hybrid-AP with LMS reduced motion in flexion-extension (FE), lateral bending (LB), and axial rotation (AR) by 77%, 88%, and 82%, respectively, compared with intact. Likewise, Hybrid-Z with LMS exhibited the greatest reduction in motion relative to intact in FE, LB, and AR by 90%, 95%, and 66%, respectively. Following simulated in vivo fatiguing, an increase in motion was observed for both groups in all planes, particularly during Hybrid-Z postfatigue condition where motion increased relative to intact by 29%. Overall, biomechanical equivalency was observed between Hybrid-AP and Hybrid-Z groups (p>.05). Three (50%) of the Hybrid-Z group specimens exhibited signs of implant migration from the inferior endplate during testing. CONCLUSIONS: Fixed profile systems using an anterior plate for supplemental fixation is biomechanically more favorable to maintain stability and prevent dislodgement. Dislodgement of 50% of the Hybrid-Z group without LMS emphasizes the necessity for posterior fixation in a zero-profile cervical hybrid decompression model.

Nilotinib as Coadjuvant Treatment with Doxorubicin in Patients with Sarcomas: A Phase I Trial of the Spanish Group for Research on Sarcoma.

Purpose: Nilotinib plus doxorubicin showed to be synergistic regarding apoptosis in several sarcoma cell lines. A phase I/II trial was thus designed to explore the feasibility of nilotinib as coadjuvant of doxorubicin by inhibiting MRP-1/P-gp efflux activity. The phase I part of the study is presented here.Patients and Methods: Nilotinib 400 mg/12 hours was administered in fixed dose from day 1 to 6, and doxorubicin on day 5 of each cycle. Three dose escalation levels for doxorubicin at 60, 65, and 75 mg/m2 were planned. Cycles were repeated every 3 weeks for a total of 4 cycles. Eligible subtypes were retroperitoneal liposarcoma, leiomyosarcoma, and unresectable/metastatic high-grade chondrosarcoma.Results: Thirteen patients were enrolled: 7 chondrosarcoma, 4 liposarcoma, and 2 leiomyosarcoma. In 46 cycles administered, the most relevant grade 3/4 adverse effects per patient were neutropenia 54%, febrile neutropenia 15%, and asthenia 8%. No cardiac toxicity was observed. Only one dose-limiting toxicity (febrile neutropenia) was reported in the third dose level. With regard to efficacy, 1 partial response (1 liposarcoma), 9 stable diseases (5 chondrosarcoma, 2 liposarcoma, 1 leiomyosarcoma), and 3 progressive diseases (2 chondrosarcoma and 1 leiomyosarcoma) were present. ABCB1 and ABCC1 RNA expression levels decreased by 58.47-fold and 1.47-fold, respectively, on day 5 of the cycle.Conclusions: Combination of MRP-1/P-gp inhibitor, nilotinib, as coadjuvant with doxorubicin is feasible; it appears not to add substantial toxicity compared with doxorubicin alone. Pharmacodynamic study supports this concept. The recommended dose for the phase II part for doxorubicin was 75 mg/m2 Clin Cancer Res; 24(21); 5239-49. ©2018 AACR.

Conduction abnormalities in the right ventricular outflow tract in Brugada syndrome detected body surface potential mapping.

Brugada syndrome (BrS) causes sudden death in patients with structurally normal hearts. Manifestation of BrS in the ECG is dynamical and most patients do not show unequivocal signs of the syndrome during ECG screening. We have obtained 67-lead body surface potential mapping recordings of 25 patients with BrS and analyzed their spatial distribution of surface potentials during ventricular activation. Six patients presented spontaneous type I ECGs during the recording. These patients showed non-dipolarities in isopotential maps at the right ventricular outflow tract (RVOT) region during the development of terminal R waves in right precordial leads. Same finding was observed in 95% of BrS patients not presenting a type I ECG. Conduction delay in the RVOT may be a consistent finding in BrS patients that can be identified by Body Surface Potential Mapping.