Background: and Purpose High-grade carotid artery stenosis may alter hemodynamics in the ipsilateral hemisphere, but consequences of this effect are poorly understood. Cortical thinning is associated with cognitive impairment in dementia, head trauma, demyelination, and stroke. We hypothesized that hemodynamic impairment, as represented by a relative time-to-peak (TTP) delay on MRI in the hemisphere ipsilateral to the stenosis, would be associated with relative cortical thinning in that hemisphere. Methods: We used baseline MRI data from the NINDS-funded Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis–Hemodynamics (CREST-H) study. Dynamic contrast susceptibility MR perfusion-weighted images were post-processed with quantitative perfusion maps using deconvolution of tissue and arterial signals. The protocol derived a hemispheric TTP delay, calculated by subtraction of voxel values in the hemisphere ipsilateral minus those contralateral to the stenosis. Results: Among 110 consecutive patients enrolled in CREST-H to date, 45 (41%) had TTP delay of at least 0.5 seconds and 9 (8.3%) subjects had TTP delay of at least 2.0 seconds, the maximum delay measured. For every 0.25-second increase in TTP delay above 0.5 seconds, there was a 0.006-mm (6 micron) increase in cortical thickness asymmetry. Across the range of hemodynamic impairment, TTP delay independently predicted relative cortical thinning on the side of stenosis, adjusting for age, sex, hypertension, hemisphere, smoking history, low-density lipoprotein cholesterol, and preexisting infarction (P=0.032). Conclusions Our findings suggest that hemodynamic impairment from high-grade asymptomatic carotid stenosis may structurally alter the cortex supplied by the stenotic carotid artery.

Dental enamel biomimetic mineralization is a process to form the enamel-like mineral structures, which possess unique microstructure and exceptional physic-chemical properties, by mimicking the mechanism of natural enamel formation and biomineralization. Varieties of techniques such as molecular mimetic synthesis and molecular self-assembling were used to accomplish the microenvironment and molecular conditions similar to that of natural tooth enamel within human body. Early remineralization and biomineralization is the future of restoration for enamel defect, research on such products have huge potential in clinical applications, with speedy advancement in recent two decades. This review summarizes the major advances in researches on enamel biomimetic mineralization in recent years.
Biomimetics ; Dental Enamel ; Humans ; Minerals

Congestive heart failure is a major cause of morbidity and mortality as well as a major health care cost in the developed world. Despite the introduction of highly effective heart failure medical therapies and simple devices such as cardiac resynchronization therapy that reduce mortality, improve cardiac function and quality of life, there remains a large number of patients who do not respond to these therapies or whose heart failure progresses despite optimal therapy. For these patients, cardiac transplantation is an option but is limited by donor availability as well as co-morbidities which may limit survival post-transplant. For these patients, left ventricular assist devices (LVADs) offer an alternative that can improve survival as well as exercise tolerance and quality of life. These devices have continued to improve as technology has improved with substantially improved durability of the devices and fewer post-implant complications. Pump thrombosis, stroke, gastrointestinal bleeding and arrhythmias post-implant have become less common with the newest devices, making destination therapy where ventricular assist device are implanted permanently in patients with advanced heart failure, a reality and an appropriate option for many patients. This may offer an opportunity for long term survival in many patients. As the first of the totally implantable devices are introduced and go to clinical trials, LVADs may be introduced that may truly be alternatives to cardiac transplantation in selected patients. Post-implant right ventricular failure remains a significant complication and better ways to identify patients at risk as well as to manage this complication must be developed.

Congestive heart failure is a major cause of morbidity and mortality as well as a major health care cost in the developed world. Despite the introduction of highly effective heart failure medical therapies and simple devices such as cardiac resynchronization therapy that reduce mortality, improve cardiac function and quality of life, there remains a large number of patients who do not respond to these therapies or whose heart failure progresses despite optimal therapy. For these patients, cardiac transplantation is an option but is limited by donor availability as well as co-morbidities which may limit survival post-transplant. For these patients, left ventricular assist devices (LVADs) offer an alternative that can improve survival as well as exercise tolerance and quality of life. These devices have continued to improve as technology has improved with substantially improved durability of the devices and fewer post-implant complications. Pump thrombosis, stroke, gastrointestinal bleeding and arrhythmias post-implant have become less common with the newest devices, making destination therapy where ventricular assist device are implanted permanently in patients with advanced heart failure, a reality and an appropriate option for many patients. This may offer an opportunity for long term survival in many patients. As the first of the totally implantable devices are introduced and go to clinical trials, LVADs may be introduced that may truly be alternatives to cardiac transplantation in selected patients. Post-implant right ventricular failure remains a significant complication and better ways to identify patients at risk as well as to manage this complication must be developed.
Arrhythmias, Cardiac ; Cardiac Resynchronization Therapy ; Exercise Tolerance ; Health Care Costs ; Heart Failure ; Heart Transplantation ; Heart-Assist Devices ; Hemorrhage ; Humans ; Mortality ; Quality of Life ; Stroke ; Thrombosis ; Tissue Donors

PURPOSE: To identify baseline prognostic factors for survival in patients with disease progression, during or after chemotherapy for the treatment of advanced gastric or gastroesophageal junction (GEJ) cancer. MATERIALS AND METHODS: We pooled data from patients randomized between 2009 and 2012 in 2 phase III, global double-blind studies of ramucirumab for the treatment of advanced gastric or GEJ adenocarcinoma following disease progression on first-line platinum- and/or fluoropyrimidine-containing therapy (REGARD and RAINBOW). Forty-one key baseline clinical and laboratory factors common in both studies were examined. Model building started with covariate screening using univariate Cox models (significance level=0.05). A stepwise multivariable Cox model identified the final prognostic factors (entry+exit significance level=0.01). Cox models were stratified by treatment and geographic region. The process was repeated to identify baseline prognostic quality of life (QoL) parameters. RESULTS: Of 1,020 randomized patients, 953 (93%) patients without any missing covariates were included in the analysis. We identified 12 independent prognostic factors of poor survival: 1) peritoneal metastases; 2) Eastern Cooperative Oncology Group (ECOG) performance score 1; 3) the presence of a primary tumor; 4) time to progression since prior therapy <6 months; 5) poor/unknown tumor differentiation; abnormally low blood levels of 6) albumin, 7) sodium, and/or 8) lymphocytes; and abnormally high blood levels of 9) neutrophils, 10) aspartate aminotransferase (AST), 11) alkaline phosphatase (ALP), and/or 12) lactate dehydrogenase (LDH). Factors were used to devise a 4-tier prognostic index (median overall survival [OS] by risk [months]: high=3.4, moderate=6.4, medium=9.9, and low=14.5; Harrell's C-index=0.66; 95% confidence interval [CI], 0.64–0.68). Addition of QoL to the model identified patient-reported appetite loss as an independent prognostic factor. CONCLUSIONS: The identified prognostic factors and the reported prognostic index may help clinical decision-making, patient stratification, and planning of future clinical studies.
Adenocarcinoma ; Alkaline Phosphatase ; Appetite ; Aspartate Aminotransferases ; Clinical Decision-Making ; Disease Progression ; Double-Blind Method ; Drug Therapy ; Esophagogastric Junction ; Factor Analysis, Statistical* ; Humans ; L-Lactate Dehydrogenase ; Lymphocytes ; Mass Screening ; Neoplasm Metastasis ; Neutrophils ; Prognosis ; Proportional Hazards Models ; Quality of Life ; Sodium ; Stomach Neoplasms*

Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.
Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Positron-Emission Tomography and Computed Tomography ; Prostate ; Prostatic Neoplasms ; Sodium Fluoride ; Sodium ; Thyroid Nodule

PURPOSE: To determine the prevalence and characteristics of neuropathic pain (NP) in patients with lumbar spinal stenosis (LSS) according to subgroup analysis of symptoms. MATERIALS AND METHODS: We prospectively enrolled subjects with LSS (n=86) who were scheduled to undergo spinal surgery. The patients were divided into two groups according to a chief complaint of radicular pain or neurogenic claudication. We measured patient's pain score using the visual analog scale (VAS), Oswestry Disability Index (ODI) and Leads Assessment of Neuropathic Symptoms and Signs (LANSS). According to LANSS value, the prevalence of NP component pain in patients with LSS was assessed. Statistical analysis was performed to find the relationship between LANSS scores and the other scores. RESULTS: From our sample of 86 patients, 31 (36.0%) had a NP component, with 24 (63.4%) in the radicular pain group having NP. However, only seven patients (15.6%) in the neurogenic claudication group had NP. The LANSS pain score was not significantly correlated with VAS scores for back pain, but did correlate with VAS scores for leg pain (R=0.73, p<0.001) and with ODI back pain scores (R=0.54, p<0.01). CONCLUSION: One-third of the patients with LSS had a NP component. The presence of radicular pain correlated strongly with NP. The severity of leg pain and ODI score were also closely related to a NP component. This data may prove useful to understanding the pain characteristics of LSS and in better designing clinical trials for NP treatment in patients with LSS.
Adult ; Aged ; Back Pain ; Decompression, Surgical ; Disability Evaluation ; Female ; Humans ; *Lumbar Vertebrae/surgery ; Male ; Middle Aged ; Neuralgia/*complications/epidemiology ; Outcome Assessment (Health Care) ; Pain Measurement/*methods ; Prevalence ; Prospective Studies ; Republic of Korea/epidemiology ; Severity of Illness Index ; Spinal Stenosis/epidemiology/*surgery ; Surveys and Questionnaires ; Treatment Outcome

OBJECTIVE: The offset connector can allow medial and lateral variability and facilitate intralaminar screw incorporation into the construct. The aim of this study was to compare the biomechanical characteristics of C7 intralaminar screw constructs with and without offset connector using a three dimensional finite element model of a C6-7 cervical spine segment. METHODS: Finite element models representing C7 intralaminar screw constructs with and without the offset connector were developed. Range of motion (ROM) and maximum von Mises stresses in the vertebra for the two techniques were compared under pure moments in flexion, extension, lateral bending and axial rotation. RESULTS: ROM for intralaminar screw construct with offset connector was less than the construct without the offset connector in the three principal directions. The maximum von Misses stress was observed in the C7 vertebra around the pedicle in both constructs. Maximum von Mises stress in the construct without offset connector was found to be 12-30% higher than the corresponding stresses in the construct with offset connector in the three principal directions. CONCLUSION: This study demonstrated that the intralaminar screw fixation with offset connector is better than the construct without offset connector in terms of biomechanical stability. Construct with the offset connector reduces the ROM of C6-7 segment more significantly compared to the construct without the offset connector and causes lower stresses around the C7 pedicle-vertebral body complex.
Biomechanics ; Immobilization ; Range of Motion, Articular ; Spine

Boney metastasis may lead to terrible suffering from debilitating pain. The most likely malignancies that spread to bone are prostate, breast, and lung. Painful osseous metastases are typically associated with multiple episodes of breakthrough pain which may occur with activities of daily living, weight bearing, lifting, coughing, and sneezing. Almost half of these breakthrough pain episodes are rapid in onset and short in duration and 44% of episodes are unpredictable. Treatment strategies include: analgesic approaches with "triple opioid therapy", bisphosphonates, chemotherapeutic agents, hormonal therapy, interventional and surgical approaches, steroids, radiation (external beam radiation, radiopharmaceuticals), ablative techniques (radiofrequency ablation, cryoablation), and intrathecal analgesics.
Activities of Daily Living ; Analgesics ; Breakthrough Pain ; Breast ; Cough ; Diphosphonates ; Lifting ; Lung ; Neoplasm Metastasis ; Prostate ; Sneezing ; Steroids ; Stress, Psychological ; Weight-Bearing

OBJECTIVE: The in vitro microculture kinetic (MiCK) apoptosis assay has been used to predict single or combination chemotherapy response in leukemia patients. This feasibility study addressed MiCK in endometrial cancer specimens. METHODS: Endometrial cancer specimens from total abdominal hysterectomies were processed at a central laboratory. Single cell suspensions of viable endometrial cancer cells were plated in individual wells. Single and combination regimens were tested: combinations of doxorubicin, cisplatin, and paclitaxel and carboplatin and paclitaxel (Gynecologic Oncology Group [GOG] 209 endometrial cancer phase III trial arms) as well as single agent testing with paclitaxel, carboplatin, doxorubicin, cisplatin, ifosfamide, and vincristine (active agents in GOG trials). Apoptosis was measured continuously over 48 hours. RESULTS: Fifteen of nineteen patients had successful assays. The highest mean chemo sensitivity was noted in the combination of cisplatin, doxorubicin, and paclitaxel with lower mean chemosensitivity for carboplatin and paclitaxel. Combination chemotherapy had higher chemosensitivity than single drug chemotherapy. However, in 25% of patients a single drug had higher chemosensitivity than combination chemotherapy. As single agents, ifosfamide, cisplatin, and paclitaxel had the highest kinetic unit values. CONCLUSION: Using a panel of agents simulating clinical dose regimens, the MiCK assay was feasible in evaluating in vitro chemosensitivity of endometrial cancer. MiCK assay results correlated with GOG clinical trial results. However, 25% of patients might be best treated with single agent chemotherapy selected by MiCK. Ifosfamide, cisplatin, and paclitaxel appear to have high activity as single agents. MiCK may be useful in future new drug testing and individualizing endometrial cancer patient's chemotherapy management.
Apoptosis ; Carboplatin ; Cisplatin ; Doxorubicin ; Drug Therapy, Combination ; Endometrial Neoplasms ; Feasibility Studies ; Female ; Humans ; Hysterectomy ; Ifosfamide ; Leukemia ; Paclitaxel ; Suspensions ; Vincristine