Lumbosarcral radiculopathties--the importance of EDX information other than needle electromyography

OBJECTIVE: This study evaluates the importance of varying electrodiagnostic (EDX) parameters abnormalities in patients with possible lumbosacral radiculopathies (LSR). METHODS: 34 patients referred for EDX studies with clinical findings consistent with a LSR without other causes for their symptoms were evaluated. Studies included not only standard (Routine EDX) nerve conduction studies (NCS) including F-waves and needle electromyography (nEMG) but also a multiparameter automated analysis system using prefabricated nerve conduction electrodes without nEMG (NC-stat EDX). RESULTS: Abnormal Routine EDX was present in 24 of the patients. Abnormal nEMG was present in only 14 of these patients, all of whom also had other relevant NCS abnormalities. Abnormal NC-stat EDX was found in 29 of the patients. In all but one patient there was agreement in the radicular localization between Routine and NC-stat EDX. In 30 patients, there was recent computed tomography or magnetic resonance imaging of the lumbosacral region. Comparable statistical agreements with the radiographic information were obtained for Routine EDX and NC-stat data. This was true including when the analyses were based on the neuroradiological evaluation of likely root injury. CONCLUSION: This study emphasizes the importance of EDX studies other than nEMG in the evaluation of patients with possible LSR and supports the value of a computerized mutliparameter methodology in these patients.     

Predictors of aneurysm occlusion following treatment with the WEB device: systematic review and case series

The Woven EndoBridge (WEB) device is becoming increasingly popular for treatment of wide-neck aneurysms. As experience with this device grows, it is important to identify factors associated with occlusion following WEB treatment to guide decision making and screen patients at high risk for recurrence. The aim of this study was to identify factors associated with adequate aneurysm occlusion following WEB device treatment in the neurosurgical literature and in our case series. A systematic review of the present literature was conducted to identify studies related to the prediction of WEB device occlusion. In addition, a retrospective review of our institutional data for patients treated with the WEB device was performed. Demographics, aneurysm characteristics, procedural variables, and 6-month follow-up angiographic outcomes were recorded. Seven articles totaling 450 patients with 456 aneurysms fit our criteria. Factors in the literature associated with inadequate occlusion included larger size, increased neck width, partial intrasaccular thrombosis, irregular shape, and tobacco use. Our retrospective review identified 43 patients with 45 aneurysms. A total of 91.1% of our patients achieved adequate occlusion at a mean follow-up time of 7.32 months. Increasing degree of contrast stasis after WEB placement on the post-deployment angiogram was significantly associated with adequate occlusion on follow-up angiogram (p?=?0.005) and with Raymond-Roy classification (p?=?0.048), but not with retreatment (p?=?0.617). In our systematic review and case series totaling 450 patients with 456 aneurysms, contrast stasis on post-deployment angiogram was identified as a predictor of adequate aneurysm occlusion, while morphological characteristics such as larger size and wide neck negatively impact occlusion.

     

“Turn the tail,not the head”: a simple,quick and inexpensive technique for the safe removal of jammed/stripped locking screws

European Journal of Orthopaedic Surgery & Traumatology - A jammed screw is a well-known complication of locking plates. Noncompliance to the standard techniques, nonusage of torque limiting...     

A molecular connection of Pterocarpus marsupium,Eugenia jambolana and Gymnema sylvestre with dipeptidyl peptidase-4 in the treatment of diabetes

Context: Pterocarpus marsupium (PM) (Leguminosae), Eugenia jambolana (EJ) (Myrtaceae) and Gymnema sylvestre (GS) (Asclepiadaceae) are the most important medicinal plants in the Indian system of traditional medicine for the treatment of hyperglycemia.

Objectives: Dipeptidyl peptidase-4 (DPP-4) inhibitors are the emerging class of anti-diabetic agents. However, only few compounds are commercially available. Therefore, in the present study we tried to explore the naturally occurring PM, EJ and GS semi-standardized extracts for their potential DPP-4 inhibition in vitro and in vivo.

Materials and methods: DPP-4 inhibition was evaluated by in vitro inhibitory assay, and enzyme kinetics were calculated using one-phase exponential decay equation. Glucose load (2?g/kg) was administered to control and diabetic rats 30?min following extract administration (100, 200 and 400?mg/kg) orally once, and blood samples were withdrawn at 0, 0.5, 1, 1.5, 2 and 3?h to measure plasma active glucagon-like peptide-1 (GLP-1) levels.

Results: PM and EJ inhibit DPP-4 potently with IC₅₀ values of 273.73?±?2.96 and 278.94?±?6.73?µg/mL, respectively, compared to GS (773.22?±?9.21?µg/mL). PM, EJ and GS exhibit long duration of action with enzyme inhibitory half-lives of 462.3, 317.2 and 153.8?min, respectively. Extracts significantly increase GLP-1 levels compared to negative control groups and peak GLP-1 level was observed at 2?h for PM and EJ, whereas for GS it was at 1.5?h

Discussion and conclusion: Taken together, results suggest the extracts may have potent DPP-4 inhibitory action, and their hypoglycemic action attributed through an increase in plasma active GLP-1 levels.     

Antidiabetic drugs and non-alcoholic fatty liver disease: A systematic review,meta-analysis and evidence map

BackgroundThe efficacy of antidiabetic agents for the treatment of non-alcoholic fatty liver disease (NAFLD) remains unclear.AimTo conduct a meta-analysis to study the efficacy of pioglitazone and three novel anti-diabetic agents: glucagon-like peptide-1 (GLP-1) agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl-peptidase-4 (DPP4) inhibitors in treating NAFLD.MethodsOnline databases were searched in May 2020 for randomized clinical trials. Results from random-effects meta-analysis are presented as weighted mean differences (WMDs) or standard mean differences (SMDs) and corresponding 95% confidence intervals (CIs).ResultsTwenty-six studies (n=946 NAFLD patients) were included. Reductions in ALT were seen with all four drugs: pioglitazone (MD -38.41, p<0.001), SGLT2 inhibitors (MD -16.17, p<0.001), GLP-1 agonists (MD -27.98, p=0.04) and DPP-4 inhibitors (MD -7.41, p<0.001). Pioglitazone (SMD -1.01; p<0.001) and GLP-1 agonists (SMD -2.53, p=0.03) also demonstrated significant improvements in liver steatosis. SGLT2 inhibitors (SMD -4.64, p=0.06) and DPP-4 (SMD -2.49, p=0.06) inhibitors trended towards reduced steatosis; however, these results were non-significant.ConclusionPioglitazone demonstrates significant improvements in transaminases and liver histology in both diabetic and non-diabetic NAFLD patients. Early evidence from diabetic NAFLD patients suggests that novel antidiabetics may lead to improvements in liver enzymes and hepatic steatosis, and this should encourage further research into possible utility of these drugs in treating NAFLD.     

Limitations of exome sequencing in detecting rare and undiagnosed diseases

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost‐effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.     

Role of peroxynitrite-modified biomolecules in the etiopathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease characterized by autoantibodies directed against various biomolecules. The initial immunogens that drive the development of SLE are unknown, but characteristics of the immune response in SLE suggest that it is an antigen-driven response, and a chromatin antigen could be one of the immunogens for the production of antinuclear antibodies (ANA) in SLE. Other factors implicated in the pathogenesis of SLE include nitrogen-free radicals such as nitric oxide and peroxynitrite. The free radical-mediated damage to proteins results in the modification of amino acid residues, cross-linking of side chains and fragmentation. The tyrosine residues in proteins are susceptible to attack by various reactive nitrogen intermediates, including peroxynitrite to form 3-nitrotyrosine (3-NT). The presence of nitrated proteins in vivo indicates that peptides derived from the proteolytic degradation of modified proteins could serve as neoantigens. Histones are highly conserved proteins that are rich in basic amino acids lysine and arginine. Autoantibodies against histones and anti-DNA antibodies are present in SLE. The anti-DNA autoantibodies coexist with anti-histone autoantibodies and may react with chromatin-associated histones and histone complexes. Elevated levels of reactive nitrogen species (RNS) in SLE patients suggest a possible role in the pathogenesis of the disease. The alteration of proteins resulting from photomodification or peroxynitrite could lead to the development of antibodies. Therefore, the modified proteins or photoadducts could have important implications in autoimmunity, and understanding the pathophysiology of peroxynitrite-modified biomolecules could lead to a better understanding of autoimmune phenomenon in SLE.