Red flags for the early detection of spinal infection in back pain patients

© 2019 The Author(s). Background: Red flags are signs and symptoms that are possible indicators of serious spinal pathology. There is limited evidence or guidance on how red flags should be used in practice. Due to the lack of robust evidence for many red flags their use has been questioned. The aim was to conduct a systematic review specifically reporting on studies that evaluated the diagnostic accuracy of red flags for Spinal Infection in patients with low back pain. Methods: Searches were carried out to identify the literature from inception to March 2019. The databases searched were Medline, CINHAL Plus, Web of Science, Embase, Cochrane, Pedro, OpenGrey and Grey Literature Report. Two reviewers screened article texts, one reviewer extracted data and details of each study, a second reviewer independently checked a random sample of the data extracted. Results: Forty papers met the eligibility criteria. A total of 2224 cases of spinal infection were identified, of which 1385 (62%) were men and 773 (38%) were women mean age of 55 (± 8) years. In total there were 46 items, 23 determinants and 23 clinical features. Spinal pain (72%) and fever (55%) were the most common clinical features, Diabetes (18%) and IV drug use (9%) were the most occurring determinants. MRI was the most used radiological test and Staphylococcus aureus (27%), Mycobacterium tuberculosis (12%) were the most common microorganisms detected in cases. Conclusion: The current evidence surrounding red flags for spinal infection remains small, it was not possible to assess the diagnostic accuracy of red flags for spinal infection, as such, a descriptive review reporting the characteristics of those presenting with spinal infection was carried out. In our review, spinal infection was common in those who had conditions associated with immunosuppression. Additionally, the most frequently reported clinical feature was the classic triad of spinal pain, fever and neurological dysfunction. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis

Abstract Amyotrophic lateral sclerosis (ALS) is a devastating and fatal motor neuron disease. Diagnosis typically occurs in the fifth decade of life and the disease progresses rapidly leading to death within ~ 2–5 years of symptomatic onset. There is no cure, and the few available treatments offer only a modest extension in patient survival. A protein central to ALS is the nuclear RNA/DNA-binding protein, TDP-43. In > 95% of ALS patients, TDP-43 is cleared from the nucleus and forms phosphorylated protein aggregates in the cytoplasm of affected neurons and glia. We recently defined that poly(ADP-ribose) (PAR) activity regulates TDP-43-associated toxicity. PAR is a posttranslational modification that is attached to target proteins by PAR polymerases (PARPs). PARP-1 and PARP-2 are the major enzymes that are active in the nucleus. Here, we uncovered that the motor neurons of the ALS spinal cord were associated with elevated nuclear PAR, suggesting elevated PARP activity. Veliparib, a small-molecule inhibitor of nuclear PARP-1/2, mitigated the formation of cytoplasmic TDP-43 aggregates in mammalian cells. In primary spinal-cord cultures from rat, Veliparib also inhibited TDP-43-associated neuronal death. These studies uncover that PAR activity is misregulated in the ALS spinal cord, and a small-molecular inhibitor of PARP-1/2 activity may have therapeutic potential in the treatment of ALS and related disorders associated with abnormal TDP-43 homeostasis

Spinal infection: state of the art and management algorithm

Spinal infection is a rare pathology although a concerning rising incidence has been observed in recent years. This increase might reflect a progressively more susceptible population but also the availability of increased diagnostic accuracy. Yet, even with improved diagnosis tools and procedures, the delay in diagnosis remains an important issue. This review aims to highlight the importance of a methodological attitude towards accurate and prompt diagnosis using an algorithm to aid on spinal infection management. METHODS: Appropriate literature on spinal infection was selected using databases from the US National Library of Medicine and the National Institutes of Health. RESULTS: Literature reveals that histopathological analysis of infected tissues is a paramount for diagnosis and must be performed routinely. Antibiotic therapy is transversal to both conservative and surgical approaches and must be initiated after etiological diagnosis. Indications for surgical treatment include neurological deficits or sepsis, spine instability and/or deformity, presence of epidural abscess and upon failure of conservative treatment. CONCLUSIONS: A methodological assessment could lead to diagnosis effectiveness of spinal infection. Towards this, we present a management algorithm based on literature findings

Does varicocele repair improve conventional semen parameters? A meta-analytic study of before-after data

Purpose The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles. Materials and Methods The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies). Results Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129–0.278; p<0.001; I2=83.62%, Egger’s p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474–1.706; p<0.001; I2=97.86%, Egger’s p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526–2.121; p<0.001; I2=97.88%, Egger’s p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318–1.968; p<0.001; I2=98.65%, Egger’s p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%–2.153%; p<0.001; I2=98.97%, Egger’s p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%–1.759%; p<0.001; l2=97.98%, Egger’s p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%–1.211%; p<0.001; I2=97.87%, Egger’s p=0.1864. Conclusions The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele. Keywords Controlled before-after studies; Infertility, male; Meta-analysis; Varicocel

Diversely substituted polyamide structures through thiol ene polymerization of renewable thiolactone building blocks

A thiolactone derivative of 10-undecenoic acid was used as a renewable AB' monomer for the one-pot synthesis of diversely substituted polyamide structures, containing amide moieties both in the polymer backbones and in their side chains. Nucleophilic aminolysis of the thiolactone entity liberates a thiol, which further reacts in a stepwise thiol-ene photopolymerization reaction. Using different primary amines, several structurally diverse polyamides, with physical properties dependent on the length and chemical identity of the side chain, were obtained. Postpolymerization oxidation of the sulfide linkages in the polymer backbone to their corresponding sulfoxides and sulfones altered the material, with the degree of oxidation having an impact on the final mechanical properties. Furthermore, this mild and straightforward polymerization procedure was applied for the synthesis of functional polymer networks

1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-ß aggregation crossing the blood-brain barrier

Given the fundamentally multifactorial character of Alzheimer's disease (AD), addressing more than one target for disease modification or therapy is expected to be highly advantageous. Here, following the cholinergic hypothesis, we aimed to inhibit both acetyl- and butyrylcholinesterase (AChE and BuChE) in order to increase the concentration of acetylcholine in the synaptic cleft. In addition, the formation of the amyloid ß fibrils should be inhibited and already preformed fibrils should be destroyed. Based on a recently identified AChE inhibitor with a 1,4-substituted 4-(1H)-pyridylene-hydrazone skeleton, a substance library has been generated and tested for inhibition of AChE, BuChE, and fibril formation. Blood-brain barrier mobility was ensured by a transwell assay. Whereas the p-nitrosubstituted compound 18C shows an anti-AChE activity in the nanomolar range of concentration (IC50 = 90 nM), the bisnaphthyl substituted compound 20L was found to be the best overall inhibitor of AChE/BuChE and enhances the fibril destruction. © 2013 Elsevier B.V.10/ECZ/012This study was partially supported by Ege University Scientific Research Project Council (Project number: 10/ECZ/012). The help of Raphael Dives in carrying out the p K a calculations is gratefully acknowledged. Appendix A -

Variables determining mortality in patients with Acinetobacter baumannii meningitis/ventriculitis treated with intrathecal colistin.

AIM: To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin. MATERIALS AND METHODS: This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis. RESULTS: Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (CI), 1.004-1.067; p=0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p=0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality. CONCLUSIONS: The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation

meningitis/ventriculitis treated with intrathecal colistin

Aim: To examine the variables associated with mortality in patients with Acinetobacter baumannii-related central nervous system infections treated with intrathecal colistin.Materials and methods: This multi-centre retrospective case control study included patients from 11 centres in Turkey, as well as cases found during a literature review. Only patients with CNS infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii treated with intrathecal colistin were included in this study. The variables associated with mortality were determined by dividing the patients into groups who died or survived during hospitalisation, and who died or survived from Acinetobacter meningitis.Results: Among the 77 cases enrolled in the study, 35 were found through a literature review and 42 were cases from our centres. Forty-four cases (57.1%) were male and the median age was 48 years (range: 20-78 years). Thirty-seven patients (48%) died during hospitalisation. The variables associated with increased all-cause mortality during hospitalisation included old age (odds ratio, 1.035; 95% confidence interval (Cl), 1.004-1.067; p = 0.026) and failure to provide cerebrospinal fluid sterilisation (odds ratio, 0.264; 95% confidence interval, 0.097-0.724; p = 0.01). There is a trend (P=0.062) towards higher mortality with using of meropenem during meningitis treatment. Fifteen cases (19%) died from meningitis. There were no significant predictors of meningitis-related mortality.Conclusions: The mortality rate for central nervous system infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii is high. Old age and failure to provide CSF sterilisation are associated with increased mortality during hospitalisation. (C) 2016 Published by Elsevier B.V