Pulsed cyclophosphamide, thalidomide and dexamethasone regimen for previously treated patients with multiple myeloma: long term follow up and disease control after subsequent treatments

There are limited data regarding the long term follow up after thalidomide based regimen and the outcome of patients when they progress and they receive further treatment. We reassessed our original series of 43 patients with previously treated multiple myeloma who had received a pulsed cyclophosphamide, thalidomide, dexamethasone (CTD) regimen. Among the 43 patients, 14 did not respond to pulsed CTD and 29 (67%) achieved at least a partial response. The median PFS for all patients was 10 months. After a median follow up of 24 months (range 1 - 62), the 3 year PFS is 14% and 3 patients remain off treatment and without progression for 55+, 55+ and 56+ months respectively. Moreover, 28% of patients who progressed after CTD achieved a partial response after subsequent treatment which included thalidomide, bortezomib or lenalidomide. The median PFS of these patients was 5 months and the 1 year PFS was 20%. Furthermore, 31% of patients who had responded to CTD and then progressed (CTD sensitive) responded to subsequent treatment. We conclude that some patients enjoy long responses after CTD and that several patients who progress after CTD may respond to treatment with a novel agent-based regimen.     

Impact of age on complications and outcome in meningioma surgery

BACKGROUND: Surgery for benign brain tumors in elderly patients without severe general health problems is an acceptable practice, as results are comparable with the ones of younger patients. Nevertheless, the hypothesis that operative complications and perioperative incidents could differ between the 2 age groups should be controlled; and age-specific strategies in operative technique and perioperative care may be useful. METHODS: Medical records of 348 patients were reviewed. Demographic data (age, sex), rate of excision, complications of the immediate postoperative period, neurological outcome, and mortality were recorded; and statistical evaluation comparing 2 age groups (19-64 and 65-84 years of age) was performed. RESULTS: The "young" age group consisted of 240 patients, whereas the "elderly" one had 108. Tumor removal rate was not significantly different in the 2 groups. The elderly age group included significantly more "complicated cases." Regarding each complication, postoperative hematoma, infections, and deep vein thrombosis were more frequent in elderly patients, presenting various degrees of statistical significance, whereas postoperative brain edema, hydrocephalus, and cardiorespiratory incidents presented no statistically significant difference. Finally, more elderly patients presented neurological deterioration, although mortality was not significantly different. CONCLUSIONS: Operation for intracranial meningioma in elderly patients is justified as long as detailed preoperative evaluation is performed. Planning of modified protocols including intraoperative technical aspects, careful use of steroids antibiotics, and prophylactic low molecular weight heparin, and early mobilization is necessary for optimizing operative outcome of elderly patients.     

Abnormal bone remodeling process is due to an imbalance in the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin (OPG) axis in patients with solid tumors metastatic to the skeleton

The role of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) system, and osteopontin (OPN) was studied in patients with solid tumors metastatic to the bone in relation to the type of malignancy and the neoplastic burden to the skeleton. Levels of soluble RANKL (sRANKL), OPG and OPN were assessed in 61 patients with breast, lung and prostate cancer with newly-diagnosed metastasis to the bone, in parallel with bone resorption [C-telopeptide of type-I collagen (CTX), tartrate-resistant acid phosphatase-5b (TRACP-5b)] and bone formation markers [bone-alkaline phosphatase (bALP), osteocalcin (OC), and C-terminal propeptide of collagen type-I (CICP)]. Patients had elevated serum levels of sRANKL, OPG, OPN, TRACP-5b, and bALP, and reduced OC levels compared to controls. OPG correlated with the extent of metastatic bone burden. Patients with breast and lung cancer shared increased levels of sRANKL, OPG, and OPN whereas prostate cancer patients had elevated values of OPG and bALP only. These results suggest that patients with solid tumors metastatic to the bone have severe disruption of the sRANKL/OPG axis. Breast and lung cancer seem to exert their osteolytic action through upregulation of the sRANKL/OPG system and OPN, whereas prostate cancer seems to provoke profound elevation of OPG levels only, thus leading to increased osteoblastic activity.     

Sustained Dyskinesias Following Elective Cessation and Reactivation of Chronic Subthalamic Nucleus Deep Brain Stimulation for a Surgical Procedure

Objectives: Subthalamic nucleus deep brain stimulation (STN DBS) is effective for treatment of levodopa‐induced dyskinesias in patients with Parkinson's disease (PD). Medical or surgical procedures requiring electrocautery may require inactivation of the pulse generators to avoid damage to the lead or extension wire or possible reprogramming of the stimulators. This generally causes only mild and temporary disability. We report a patient with previously well‐controlled dyskinesias who had severe and prolonged dyskinesias following reactivation of deep brain stimulation (DBS) following an orthopedic procedure. Materials and Methods: Retrospective chart review. Results: The patient underwent two orthopedic procedures, each requiring inactivation of DBS. After reactivation of DBS, the patient experienced severe dyskinesias that ultimately required sedation and ventilation to control large‐amplitude dyskinesias. Conclusions: Clinicians caring for PD patients treated with STN DBS should be aware of the possible reappearance of severe dyskinesias arising from routine inactivation and reactivation of pulse generators for medical or surgical procedures.     

Efficacy of Various “Classic” Echocardiographic and Laboratory Indices in Distinguishing the “Gray Zone” between Athlete's Heart and Hypertrophic Cardiomyopathy: A Pilot Study

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5 cm in athletes represents a “gray zone” between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the “gray zone” entities. Aim of this study was to assess the efficacy of these “classic” parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28 ± 0.07 cm), 9 patients with mild HCM (1.38 ± 0.11 cm), and 26 athletes without LVH (1.06 ± 0.09 cm; P < 0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between “gray zone” groups. After bootstrapping analysis, it was found that athletes with left ventricular end‐diastolic diameter <4.74 cm, mitral deceleration time >200 ms, isovolumic relaxation time >94 ms, tricuspid E/A < 1.63, septum Em < 9.5 cm/sec, relative wall thickness >0.445, and a BNP value at rest >9.84 pg/mL had a greater possibility for having underlying cardiomyopathy. A 10‐point score based on these parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738–1.0; P = 0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP.     

In Silico Screening-Level Prioritization of 8468 Chemicals Produced in OECD Countries to Identify Potential Planetary Boundary Threats

Bulletin of Environmental Contamination and Toxicology - Legislation such as the Stockholm Convention and REACH aim to identify and regulate the production and use of chemicals that qualify as...     

Development of HLA-matched vascular grafts utilizing decellularized human umbilical artery

Worldwide, there is a great need of small diameter vascular grafts that can be used in human disorders such as cardiovascular and peripheral vascular disease. Until now, severe adverse reactions are caused from the use of synthetic or animal derived grafts, while the use of autologous vessels is restricted only in a small number of patients. The limited availability of the vessels might be resolved by the use of HLA-matched vascular grafts utilizing the decellularized human umbilical arteries. In this study, human umbilical arteries were decellularized and then repopulated with Mesenchymal Stem Cells. The HLA-genotype of the repopulated grafts, analyzed by Next Generation Sequencing technology, indicated their successful production. The HLA-matched vascular grafts could be generated efficiently and might be used in personalized medicine.