Associations between self-reported sleep quality and cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease.

Sleep disorders are very common in mild cognitive impairment (MCI) and Alzheimer's disease (AD). Several parameters of polysomnography seem to correlate with cognitive scores and amyloid biomarkers in the different stages of AD. However, there is limited evidence for the relationship between self-reported sleep impairment and disease biomarkers. In this study, we assessed the relationship between self-reported sleep complaints, with the Pittsburgh Sleep Quality Index, and both cognitive function and cerebrospinal fluid biomarkers in 70 patients with MCI and 78 patients with AD. Sleep duration and daytime dysfunction were higher in AD. Daytime dysfunction had a negative correlation with cognitive scores (Mini-Mental-State Examination and Montreal Cognitive Assessment) and with amyloid-beta1-42 protein, and a positive correlation with total tau protein. However, daytime dysfunction was an independent predictor only of t-tau values (F=57.162; 95% CI: [18.118; 96.207], P=0.004). These findings support a relationship between daytime dysfunction, cognitive scores and neurodegeneration, further expanding recent findings that it may signal a risk of dementia.

CSF Tau proteins reduce misdiagnosis of sporadic Creutzfeldt-Jakob disease suspected cases with inconclusive 14-3-3 result.

Cerebrospinal fluid (CSF) 14-3-3 protein supports sporadic Creutzfeldt-Jakob (sCJD) diagnosis, but often leads to weak-positive results and lacks standardization. In this study, we explored the added diagnostic value of Total Tau (t-Tau) and phosphorylated Tau (p-Tau) in sCJD diagnosis, particularly in the cases with inconclusive 14-3-3 result. 95 definite sCJD and 287 patients without prion disease (non-CJD) were included in this study. CSF samples were collected in routine clinical diagnosis and analysed for 14-3-3 detection by Western blot (WB). CSF t-Tau and p-Tau were quantified by commercial ELISA kits and PRNP and APOE genotyping assessed by PCR-RFLP. In a regression analysis of the whole cohort, 14-3-3 protein revealed an overall accuracy of 82 % (sensitivity = 96.7 %; specificity = 75.6 %) for sCJD. Regarding 14-3-3 clear positive results, we observed no added value either of t-Tau alone or p-Tau/t-Tau ratio in the model. On the other hand, considering 14-3-3 weak-positive cases, t-Tau protein increased the overall accuracy of 14-3-3 alone from 91 to 94 % and specificity from 74 to 93 % (p < 0.05), with no sensitivity improvement. However, inclusion of p-Tau/t-Tau ratio did not significantly improve the first model (p = 0.0595). Globally, t-Tau protein allowed a further discrimination of 65 % within 14-3-3 inconclusive results. Furthermore, PRNP MV genotype showed a trend to decrease 14-3-3 sensitivity (p = 0.051), but such effect was not seen on t-Tau protein. In light of these results, we suggest that t-Tau protein assay is of significant importance as a second marker in identifying 14-3-3 false-positive results among sCJD probable cases.

Sporadic Creutzfeldt-Jakob disease diagnostic accuracy is improved by a new CSF ELISA 14-3-3γ assay.

Protein 14-3-3 is a reliable marker of rapid neuronal damage, specifically increased in cerebrospinal fluid (CSF) of sporadic Creutzfeldt-Jakob disease (sCJD) patients. Its detection is usually performed by Western Blot (WB), prone to methodological issues. Our aim was to evaluate the diagnostic performance of a recently developed quantitative enzyme-linked immunosorbent (ELISA) assay for 14-3-3γ, in comparison with WB and other neurodegeneration markers. CSF samples from 145 patients with suspicion of prion disease, later classified as definite sCJD (n=72) or Non-prion diseases (Non-CJD; n=73) comprised our population. 14-3-3 protein was determined by WB and ELISA. Total Tau (t-Tau) and phosphorylated Tau (p-Tau) were also evaluated. Apolipoprotein E gene (ApoE) and prionic protein gene (PRNP) genotyping was assessed. ELISA 14-3-3γ levels were significantly increased in sCJD compared to Non-CJD patients (p<0.001), showing very good accuracy (AUC=0.982; sensitivity=97%; specificity=94%), and matching WB results in 81% of all cases. It strongly correlated with t-Tau and p-Tau (p<0.0001), showing slightly higher specificity (14-3-3 WB - 63%; Tau - 90%; p-Tau/t-Tau ratio - 88%). From WB inconclusive results (n=44), ELISA 14-3-3γ correctly classified 41 patients. Additionally, logistic regression analysis selected ELISA 14-3-3γ as the best single predictive marker for sCJD (overall accuracy=93%). ApoE and PRNP genotypes did not influence ELISA 14-3-3γ levels. Despite specificity for 14-3-3γ isoform, ELISA results not only match WB evaluation but also help discrimination of inconclusive results. Our results therefore reinforce this assay as a single screening test, allowing higher sample throughput and unequivocal results.

Treatment of benign hepatic cysts by instillation of tetracycline hydrochloride.

BACKGROUND/AIMS: Despite the high frequency of benign hepatic cysts, they rarely cause symptoms. Large cysts, however, may produce clinical manifestations. In these cases, ultrasonography-guided therapy has been proposed. We report the results of this therapy in patients with symptomatic benign hepatic cysts. METHODOLOGY: Seven patients with non-parasitic, non-neoplastic benign hepatic cysts were submitted to fine-needle ultrasonography-guided aspiration, followed by injection of diluted tetracycline hydrochloride (1 g). In all cases, cytology, tumour markers and microbiology analysis of aspirates were performed. One patient required two sessions. The grade of patient satisfaction and ultrasonography changes were assessed 1, 3 and 6 months after the procedure. RESULTS: Cyst size decreased in all patient, with total collapse in three. No major complications occurred. Cytology, alpha fetoprotein, CA19.9, CEA and microbiology of the cyst fluid confirmed the initial ultrasonographic diagnosis of simple biliary cysts. Clinical complaints improved in 2 cases, and 5 patients became asymptomatic. Ultrasonography evaluation 3 months after the procedure was more reliable in predicting successful treatment. CONCLUSION: Intracystic instillation of tetracycline hydrochloride is an effective and safe technique and may become the first choice therapy for benign hepatic cysts.

Management of tumor overgrowth in esophageal cancer by placement of a second stent: two case reports.

We present two cases of tumor overgrowth after stenting in patients with inoperable esophageal cancers that were managed by placement of a second tube. The macroscopic pattern of the tumor overgrowth was infiltrative, contraindicating it for laser therapy. Dysphagia was solved in both patients by insertion of expandable metal stents.