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In the last years, clusterin, a challenging and paradoxical apolipoprotein,has been of growing interest amongst a rising number of scientists. This enigmatic protein is present in all fluids of the organism besides within the intracellular matrix, and it plays diverse, and at times contrary, roles in a growing number of pathologies. It seems to vary its location and function to assure cellular survival being cytoprotective hence its significance in neuroprotection and cancer along with chemotherapy resistance. However, it can also lead to cellular arrest and its modulation to apoptosis. Additionally, it has been described to modulate pain, as well as linked to inflammation, cardioprotection, satiety and hunger, and possibly to addictive behaviour development .Thus, it has been postulated to be used both as a biomarker and a very explorable new therapeutic target for several conditions.

ImportancePeripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central nervous system, and less is known about their role in the peripheral nervous system.ObjectiveTo assess blood-based biomarker concentrations associated with nerve involvement in patients with peripheral neuropathy compared with control participants.Data SourcesOvid, MEDLINE, Embase, and CINAHL were searched from inception to September 23, 2021.Study SelectionObservational studies reporting on blood biomarkers in patients diagnosed with peripheral neuropathy were included. This review was preregistered on PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were abstracted by 1 investigator and independently reviewed by a second.Data Extraction and SynthesisData were meta-analyzed when at least 2 studies reported the same biomarker with comparable methodology. Fixed-effects models were used when only 2 studies were included; random-effects models were used when more than 2 studies were included.Main Outcomes and MeasuresThe outcome of interest was concentration of biomarkers.ResultsThis review included 36 studies reporting on 4414 participants, including 2113 control participants and 2301 patients with peripheral neuropathy with 13 distinct peripheral neuropathy diagnoses. Diabetic neuropathy was the most common neuropathy diagnosis (13 studies), followed by Charcot-Marie-Tooth disease (6 studies) and Guillain-Barre syndrome (6 studies). Overall, 16 different blood-based biomarkers associated with nerve involvement were evaluated. The most used were neurofilament light chain, S100B, brain-derived neurotrophic factor, and neuron-specific enolase. Patients with peripheral neuropathy demonstrated significantly higher levels of neurofilament light chain compared with controls (standardized mean difference [SMD], 0.93 [95% CI, 0.82 to 1.05]; P < .001). There were no significant differences in levels of S100B (SMD, 1.10 [95% CI, −3.08 to 5.28]; P = .38), brain-derived neurotrophic factor (SMD, −0.52 [95% CI, −2.23 to 1.19]; P = .40), or neuron-specific enolase (SMD, −0.00 [95% CI, −1.99 to 1.98]; P = .10) in patients with peripheral neuropathy compared with control participants.Conclusions and RelevanceThe findings of this systematic review and meta-analysis support the use of neurofilament light chain as a blood-based measure associated with the presence of neuronal injury in patients with peripheral neuropathy.

Purpose: Background: Evaluate whether the design of placebo control groups could produce different interpretations of the efficacy of manual therapy techniques. Methods: Nine databases were searched (EMBASE, CINAHL, PsycINFO, MEDLINE, PubMed, SCOPUS, WEB of SCIENCE, COCHRANE, and PEDro). Randomized placebo-controlled clinical trials that used manual therapy as a sham treatment on subjects suffering from pain were included. Data were summarized qualitatively, and meta-analyses were conducted with R. Results: 53 articles were included in the qualitative analysis and 48 were included in the quantitative analyses. Manipulation techniques did not show higher effectiveness when compared with all types of sham groups that were analyzed (SMD 0.28; 95%CI [−0.24; 0.80]) (SMD 0.28; 95%CI [−0.08; 0.64]) (SMD 0.42; 95%CI [0.16; 0.67]) (SMD 0.82; 95%CI [−0.57; 2.21]), raising doubts on their therapeutic effect. Factors such as expectations of treatment were not consistently evaluated, and analysis could help clarify the effect of different sham groups. As for soft tissue techniques, the results are stronger in favor of these techniques when compared to sham control groups (SMD 0.40; 95%CI [0.19, 0.61]). Regarding mobilization techniques and neural gliding techniques, not enough studies were found for conclusions to be made. Conclusions: The literature presents a lack of a unified placebo control group design for each technique and an absence of assessment of expectations. These two issues might account for the unclear results obtained in the analysis.