Accuracy of preoperative endo-rectal coil magnetic resonance imaging in detecting clinical under-staging of localized prostate cancer

Objectives

To assess the accuracy of intra-rectal coil magnetic resonance imaging (ER-MRI) for staging early prostate cancer (EPC).

Materials and methods

ER-MRI was performed with the Magnetom Symphony 1.5 Tesla system. ER-MRI and pathology findings were statistically correlated.

Results

One hundred and fifty-four consecutive patients underwent radical prostatectomy (RRP) for EPC (cT1c-2 Nx M0). An average age was 66, mean PSA 11.04 µg/L (median 7.33 µg/L) and mean pathologic Gleason score 6. Pathology detected 97 out of 154 patients (63 %) as EPC and 57 cases (37 %) as extra-prostate extension (EPED) (pT3) with extra-capsular extension (ECE) (pT3a) in 41 (27 %) and seminal vesicle invasion (SVI) (pT3b) in 16 (10 %). ER-MRI staged 100 patients (65 %) as cT2 and 54 (35 %) as EPED with ECE in 37 cases (24 %) and SVI in 17 (11 %). ER-MRI sensitivity, specificity, positive predictive value, negative predictive value, overall accuracy resulted respectively 0.78, 0.96, 0.86, 0.92, 0.91 for ECE as well as 0.88, 0.98, 0.82, 0.99 and 0.97 for SVI.

Conclusion

ER-MRI was effective in detecting preoperative EPC under-staging. In the next future, multi-parametric 3-Tesla ER-MRI will be the procedure for diagnosing, staging and following-up prostate cancer patients.     

Stiffness as a presenting symptom of an odd clinical condition caused by multiple sclerosis and myotonia congenita

A 24-year-old woman complained of a 4-year history of muscle cramps, stiffness of the right lower limb and walking difficulties. After clinical and laboratory investigations, a diagnosis of multiple sclerosis was made. However, her family history revealed that her father and an older sister had lifelong symptoms of impaired muscle relaxation following contraction, improving with physical exercise. Molecular genetic studies in both sisters confirmed the diagnosis of myotonia congenita, due to a c.568GG>TC (Gly190Ser) pathogenic mutation in CLCN1 gene. Occurrence of two different neurological conditions in the same patient, both manifesting with stiffness, is quite unusual and suggests the opportunity of an accurate differential diagnosis.     

Modern drug delivery strategies applied to natural active compounds

Introduction: Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules.

Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability.

Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, ‘discovering ex novo’ unexpected virtues and benefits associated to these compounds. The ‘nanotechnological approach’ can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.     

Prolonged distal motor latency of median nerve does not improve diagnostic accuracy for CIDP

Journal of Neurology - Compression of the median nerve at the carpal tunnel can give demyelinating features and result in distal motor latency (DML) prolongation fulfilling the EFNS/PNS...     

Remote cerebellar hemorrhage after spinal procedures (part 2): a systematic review

A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which can be rarely observed as a complication of spine surgery. As well as for RCH reported after supratentorial procedures, it shows a characteristic bleeding pattern defined “zebra sign”. Nowadays, RCH pathophysiology still remains unknown. We performed a comprehensive review, collecting all cases of RCH after spine surgery reported in literature in order to identify the procedures most frequently associated with RCH and the possible risk factors. We assessed percentages of incidence and 95 % confidence interval of all demographic, neuroradiological, and clinical features. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 44 articles reporting 57 patients with mean age of 57.6?±?13.9 years and a male/female ratio of 23/34. A RCH was more frequently reported as a complication of decompressive procedures for spinal canal stenosis, particularly when associated with instrumented fusion, followed by spinal tumor debulking and disc herniation removal. In the majority of cases, RCH occurrence was characterized by progressive impairment of consciousness, whereas some patients complained non-specific symptoms. Coagulation disorders, hypertension, and placement of postoperative subfascial drainages were the most frequently reported risk factors. The occurrence of intraoperative dural lesions was described in about 93 % of patients. Zebra sign was the most common bleeding pattern (about 43 % of cases) followed by parenchymal hematoma (37.5 %) and mixed hemorrhage (about 20 %). Impairment of consciousness at clinical onset and intake of anticoagulants/antiplatelets appeared associated with poor outcome at univariate analysis. However, more than 75 % of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless of the occurrence of complications.     

Hepatocyte growth factor (HGF) and hemodialysis: physiopathology and clinical implications

Hepatocyte growth factor (HGF) is a pleiotropic cytokine which exerts a variety of effects on several cells, being involved in the regulation of many biological processes, such as inflammation, tissue repair, morphogenesis, angiogenesis, tumour propagation, immunomodulation of viral infections and cardio-metabolic activities. Patients undergoing regular hemodialysis (HD) present elevated levels of HGF, mainly due to the leukocyte activation associated with HD treatment. High HGF levels might account for specific clinical features of HD patients, i.e. mild liver damage in course of HCV-infection and high cardiovascular risk profile. Moreover, in patients with acute kidney injury, the induction of HGF may represent a crucial step to promote renal recovery, which can have important prognostic consequences in the short and long-term. In this review we discuss the mechanisms underlying HGF production in HD patients, the role of HGF in this particular patient population and the potential clinical implications derived from the study of HGF in HD patients.     

Circulating SIRT1 Increases After Intragastric Balloon Fat Loss in Obese Patients

Background

Sirtuins (SIRTs), ubiquitous deacetylases, are main regulators of energy homeostasis and metabolism. SIRT1 has a positive impact on obesity, diabetes mellitus, liver steatosis, and other metabolic disorders. Lean subjects have higher expression of SIRT1 in the adipose tissue compared to obese. However, it is not known whether weight loss associates with changes in blood SIRT1. We evaluated the effect of weight loss on circulating SIRT1, metabolic parameters, and body composition.

Methods

Thirty-two obese subjects were studied before and 6 months after BioEnterics® Intragastric Balloon (BIB®) [22 patients, BMI 41.82?±?6.28 kg/m²] or hypocaloric diet [10 patients, BMI 38.95?±?6.90 kg/m²]. Plasma SIRT1, body composition, measures of metabolic syndrome (waist circumference, fasting plasma glucose, blood pressure, HDL cholesterol, triglycerides), and inflammation markers (ESR, CRP, fibrinogen) were recorded.

Results

SIRT1 levels showed a significant increase, together with a significant reduction of BMI, excess body weight, and total fat mass either after BIB or diet intervention. The percent excess body weight loss was 33.73?±?19.06 and 22.08?±?11.62 % after BIB and diet, respectively, a trend toward a metabolic and inflammatory amelioration was observed with both treatments. Negative correlation between SIRT1 and % fat mass (BIB, ρ?=??0.537, p?=?0.017; diet, ρ?=??0.638, p?=?0.047) was also seen.

Conclusions

The reduction of fat mass associates with increased plasma SIRT1 indicating that, besides tissue levels, circulating SIRT1 is stimulated by a negative caloric balance. The rise of plasma SIRT1 may represent a parameter associating with fat loss rather than weight lowering regardless of the weight reduction system method used.

     

Biochemical analysis of TEM-134, a new TEM-type extended-spectrum beta-lactamase variant produced in a Citrobacter koseri clinical isolate from an Italian hospital

OBJECTIVES: Kinetic characterization of TEM-134, a new TEM-type extended-spectrum beta-lactamase variant isolated from Citrobacter koseri during an Italian nationwide survey. TEM-134 is a natural derivative of TEM-2 with the following substitutions: E104K, R164H and G238S. METHODS: Recombinant TEM-134 was purified from Escherichia coli HB101 (pMGP-134) by three chromatographic steps (cation-exchange chromatography, gel permeation and fast chromatofocusing). Steady-state kinetic parameters (K(m) and k(cat)) were determined by measuring substrate hydrolysis under initial rate conditions using the Hanes linearization of the Michaelis-Menten equation. Modelling was carried out using the software Modeller (version 9.1). RESULTS: TEM-134 hydrolysed with variable efficiency (k(cat)/K(m) ranging from 5 x 10(3) to 8.0 x 10(5) M(-1) . s(-1)) penicillins, narrow-spectrum cephalosporins, cefepime, cefotaxime, ceftazidime and aztreonam, which appeared to be the best substrate. Molecular modelling of the enzyme indicated that the R164H substitution may result in a compromised omega loop in TEM-134 and this may be responsible for its narrower spectrum of activity. CONCLUSIONS: Kinetic data and molecular modelling suggested that R164H has a mild detrimental effect on the global activity of the enzyme.