BackgroundStrongyloides stercoralis infection is a neglected tropical disease which can lead to severe symptoms and even death in immunosuppressed people. Unfortunately, its diagnosis is hampered by the lack of a gold standard, as the sensitivity of traditional parasitological tests (including microscopic examination of stool samples and coproculture) is low. Hence, alternative diagnostic methods, such as molecular biology techniques (mostly polymerase chain reaction, PCR) have been implemented. However, there are discrepancies in the reported accuracy of PCR.MethodologyA systematic review with meta-analysis was conducted in order to evaluate the accuracy of PCR for the diagnosis of S. stercoralis infection. The protocol was registered with PROSPERO International Prospective Register of Systematic Reviews (record: CRD42016054298). Fourteen studies, 12 of which evaluating real-time PCR, were included in the analysis. The specificity of the techniques resulted high (ranging from 93 to 95%, according to the reference test(s) used). When all molecular techniques were compared to parasitological methods, the sensitivity of PCR was assessed at 71.8% (95% CI 52.2–85.5), that decreased to 61.8% (95% CI 42.0–78.4) when serology was added among the reference tests. Similarly, sensitivity of real-time PCR resulted 64.4% (95% CI 46.2–77.7) when compared to parasitological methods only, 56.5% (95% CI 39.2–72.4) including serology.ConclusionsPCR might not be suitable for screening purpose, whereas it might have a role as a confirmatory test.

We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

Strongyloides stercoralis, a worldwide-distributed soil-transmitted helminth, causes chronic infection which may be life threatening. Limitations of diagnostic tests and nonspecificity of symptoms have hampered the estimation of the global morbidity due to strongyloidiasis. This work aimed at assessing S. stercoralis-associated morbidity through a systematic review and meta-analysis of the available literature. MEDLINE, Embase, CENTRAL, LILACS, and trial registries (WHO portal) were searched. The study quality was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) of the association between symptoms and infection status and frequency of infection-associated symptoms were calculated. Six articles from five countries, including 6,014 individuals, were included in the meta-analysis-three were of low quality, one of high quality, and two of very high quality. Abdominal pain (OR 1.74 [CI 1.07-2.94]), diarrhea (OR 1.66 [CI 1.09-2.55]), and urticaria (OR 1.73 [CI 1.22-2.44]) were associated with infection. In 17 eligible studies, these symptoms were reported by a large proportion of the individuals with strongyloidiasis-abdominal pain by 53.1% individuals, diarrhea by 41.6%, and urticaria by 27.8%. After removing the low-quality studies, urticaria remained the only symptom significantly associated with S. stercoralis infection (OR 1.42 [CI 1.24-1.61]). Limitations of evidence included the low number and quality of studies. Our findings especially highlight the appalling knowledge gap about clinical manifestations of this common yet neglected soil-transmitted helminthiasis. Further studies focusing on morbidity and risk factors for dissemination and mortality due to strongyloidiasis are absolutely needed to quantify the burden of S. stercoralis infection and inform public health policies.

Cystic echinococcosis (CE) is a neglected zoonosis caused by infection with the cestode Echinococcus granulosus sensu lato. We carried out a systematic literature review on E. granulosus s.l. human and animal (cattle, sheep, dog) infection in European Mediterranean and Balkan countries in 2000-2019, to provide a picture of its recent epidemiology in this endemic area. MEDLINE, EMBASE, Scopus, Google Scholar and Open Grey databases were searched. Included cases were: i) for humans, data from hospital records and imaging studies; ii) for dogs, data from necropsy and coprological studies; iii) for ruminants, cases based on slaughter inspection. The NUTS (Nomenclature of Territorial Units for Statistics) classification was used to categorize extracted data in epidemiological units, defined as data referred to one NUTS2 (basic region) in one year time. Data were then aggregated to NUTS1 level (major regions), calculating the average incidence value of included epidemiological units. For prevalence studies covering different epidemiological units, the pooled prevalence was estimated. Data were extracted from 79 publications, 25 on human infection (covering 437 epidemiological units), and 54 on animal infection (52 epidemiological units for cattle, 35 for sheep and 25 for dogs). At NUTS1 level, average annual incidence rates of human CE ranged from 0.10-7.74/ 100,000; pooled prevalence values ranged from 0.003-64.09% in cattle, 0.004-68.73% in sheep, and 0-31.86% in dogs. Southern and insular Italy, central Spain, Romania and Bulgaria reported the highest values. Bovine data showed a more similar pattern to human data compared to sheep and dogs. Limitation of evidence included the paucity of human prevalence studies, data heterogeneity, and the patchy geographical coverage, with lack of data especially for the Balkans. Our results confirm Italy, Spain, and Eastern Europe being the most affected areas, but data are extremely heterogeneous, geographical coverage very patchy, and human prevalence studies extremely scant. Results also highlight the notorious problem of underreporting of E. granulosus s.l. infection in both humans and animals.

Liver lipid accumulation is a hallmark of non-alcoholic fatty liver disease (NAFLD), broadly associated with insulin resistance. Inositols (INS) are ubiquitous polyols implied in many physiological functions. They are produced endogenously, are present in many foods and in dietary supplements. Alterations in INS metabolism seems to play a role in diseases involving insulin resistance such as diabetes and polycystic ovary syndrome. Given its role in other metabolic syndromes, the hypothesis of an INS role as a supplement in NAFLD is intriguing. We performed a systematic review of the literature to find preclinical and clinical evidence of INS supplementation efficacy in NAFLD patients. We retrieved 10 studies on animal models assessing Myoinosiol or Pinitol deficiency or supplementation and one human randomized controlled trial (RCT). Overall, INS deficiency was associated with increased fatty liver in animals. Conversely, INS supplementation in animal models of fatty liver reduced hepatic triglycerides and cholesterol accumulation and maintained a normal ultrastructural liver histopathology. In the one included RCT, Pinitol supplementation obtained similar results. Pinitol significantly reduced liver fat, post-prandial triglycerides, AST levels, lipid peroxidation increasing glutathione peroxidase activity. These results, despite being limited, indicate the need for further evaluation of INS in NAFLD in larger clinical trials.

Background Hepatosplenic schistosomiasis (HSS) is a disease caused by chronic infection with Schistosma spp. parasites residing in the mesenteric plexus; portal hypertension causing gastrointestinal bleeding is the most dangerous complication of this condition. HSS requires complex clinical management, but no specific guidelines exist. We aimed to provide a comprehensive picture of consolidated findings and knowledge gaps on the diagnosis and treatment of HSS. Methodology/principal findings We reviewed relevant original publications including patients with HSS with no coinfections, published in the past 40 years, identified through MEDLINE and EMBASE databases. Treatment with praziquantel and HSS-associated pulmonary hypertension were not investigated. Of the included 60 publications, 13 focused on diagnostic aspects, 45 on therapeutic aspects, and 2 on both aspects. Results were summarized using effect direction plots. The most common diagnostic approaches to stratify patients based on the risk of variceal bleeding included the use of ultrasonography and platelet counts; on the contrary, evaluation and use of noninvasive tools to guide the choice of therapeutic interventions are lacking. Publications on therapeutic aspects included treatment with beta-blockers, local management of esophageal varices, surgical procedures, and transjugular intrahepatic portosystemic shunt. Overall, treatment approaches and measured outcomes were heterogeneous, and data on interventions for primary prevention of gastrointestinal bleeding and on the long-term follow-up after interventions were lacking. Conclusions Most interventions have been developed on the basis of individual groups’ experiences and almost never rigorously compared; furthermore, there is a lack of data regarding which parameters can guide the choice of intervention. These results highlight a dramatic need for the implementation of rigorous prospective studies with long-term follow-up in different settings to fill such fundamental gaps, still present for a disease affecting millions of patients worldwide.

Background: Antithrombotic treatment, including low molecular weight heparin (LMWH) or unfractionated heparin (UFH), has been proposed as a potential therapy for coronavirus disease 2019 (COVID-19) to lower diffuse intravascular clotting activation. However, it is unclear whether prophylactic or therapeutic doses have similar efficacy in reducing mortality.Methods: We performed a systematic review (PROSPERO registration CRD42020179955) and meta-analysis including observational cohort studies and randomized controlled trials (RCT) evaluating the effectiveness of heparins (either LMWH, UFH, or fondaparinux) in COVID-19 patients. Heparin treatment was compared to no anticoagulation. A subgroup analysis on prophylactic or therapeutic doses compared to no anticoagulation was performed. Prophylactic dose was also compared to full dose anticoagulation. Primary endpoint was all-cause mortality. Secondary endpoints were major bleeding and length of hospital stay (LOS).Results: 33 studies (31 observational, 2 RCT) were included for a total overall population of 32,688 patients. Of these, 21,723 (66.5%) were on heparins. 31 studies reported data on all-cause mortality, showing that both prophylactic and full dose reduced mortality (pooled Hazard Ratio [HR] 0.63, 95% confidence interval [CI] 0.57-0.69 and HR 0.56, 95% CI 0.47-0.66, respectively). However, the full dose was associated with a higher risk of major bleeding (Odds Ratio [OR] 2.01, 95% CI 1.14–3.53) compared to prophylactic dose. Finally, LOS was evaluated in 3 studies; no difference was observed between patients with and without heparins (0.98, −3.87, 5.83 days).Conclusion: Heparin at both full and prophylactic dose is effective in reducing mortality in hospitalized COVID-19 patients, compared to no treatment. However, full dose was associated with an increased risk of bleeding.Systematic Review Registration: https://clinicaltrials.gov/, identifier CRD42020179955

The amount of knowledge on human consciousness has created a multitude of viewpoints and it is difficult to compare and synthesize all the recent scientific perspectives. Indeed, there are many definitions of consciousness and multiple approaches to study the neural correlates of consciousness (NCC). Therefore, the main aim of this article is to collect data on the various theories of consciousness published between 2007–2017 and to synthesize them to provide a general overview of this topic. To describe each theory, we developed a thematic grid called the dimensional model, which qualitatively and quantitatively analyzes how each article, related to one specific theory, debates/analyzes a specific issue. Among the 1130 articles assessed, 85 full texts were included in the prefinal step. Finally, this scoping review analyzed 68 articles that described 29 theories of consciousness. We found heterogeneous perspectives in the theories analyzed. Those with the highest grade of variability are as follows: subjectivity, NCC, and the consciousness/cognitive function. Among sub-cortical structures, thalamus, basal ganglia, and the hippocampus were the most indicated, whereas the cingulate, prefrontal, and temporal areas were the most reported for cortical ones also including the thalamo-cortical system. Moreover, we found several definitions of consciousness and 21 new sub-classifications.