Evaluating Infectious, Neoplastic, Immunological, and Degenerative Diseases of the Central Nervous System with Cerebrospinal Fluid-Based Next-Generation Sequencing.

Cerebrospinal fluid (CSF) is a clear and paucicellular fluid that circulates within the ventricular system and the subarachnoid space of the central nervous system (CNS), and diverse CNS disorders can impact its composition, volume, and flow. As conventional CSF testing suffers from suboptimal sensitivity, this review aimed to evaluate the role of next-generation sequencing (NGS) in the work-up of infectious, neoplastic, neuroimmunological, and neurodegenerative CNS diseases. Metagenomic NGS showed improved sensitivity-compared to traditional methods-to detect bacterial, viral, parasitic, and fungal infections, while the overall performance was maximized in some studies when all diagnostic modalities were used. In patients with primary CNS cancer, NGS findings in the CSF were largely concordant with the molecular signatures derived from tissue-based molecular analysis; of interest, additional mutations were identified in the CSF in some glioma studies, reflecting intratumoral heterogeneity. In patients with metastasis to the CNS, NGS facilitated diagnosis, prognosis, therapeutic management, and monitoring, exhibiting higher sensitivity than neuroimaging, cytology, and plasma-based molecular analysis. Although evidence is still rudimentary, NGS could enhance the diagnosis and pathogenetic understanding of multiple sclerosis in addition to Alzheimer and Parkinson disease. To conclude, NGS has shown potential to aid the research, facilitate the diagnostic approach, and improve the management outcomes of all the aforementioned CNS diseases. However, to establish its role in clinical practice, the clinical validity and utility of each NGS protocol should be determined. Lastly, as most evidence has been derived from small and retrospective studies, results from randomized control trials could be of significant value.

Aeromonas hydrophila Survives the Treatment of Posttraumatic Cellulitis in the Shelter of an Obscured Fish-Bone Fragment.

Fish bone and/or spine puncture injuries can result in infection of the upper extremities with aquatic bacterial pathogens. Additionally, in such injuries, the inoculation of foreign organic material is frequent and may further complicate the clinical presentation and course of the resulting infection. We describe the case of a 45-year-old female patient with a minimal fish rostrum puncture trauma acquired during preparation of fresh fish meal, which resulted in a galloping hand cellulitis. The alarming clinical presentation and the prompt response of the skin infection to clindamycin obscured the presence of inoculated fish rostrum remnants in the tissue that, three weeks later, gave rise to a foreign body granuloma, from which Aeromonas hydrophila was isolated. Final resolution was achieved with an additional two-week doxycycline treatment. In conclusion, the reported case highlights the potential of the accidentally implanted organic material, as are fish bones, not only to transfer uncommon pathogens but also to offer a sanctuary that favors microbial survival despite antibiotic therapy thus enabling latent or recurrent infections.

Nutritional Status and the Influence of the Vegan Diet on the Gut Microbiota and Human Health.

The human gut microbiota is considered a well-known complex ecosystem composed of distinct microbial populations, playing a significant role in most aspects of human health and wellness. Several factors such as infant transitions, dietary habits, age, consumption of probiotics and prebiotics, use of antibiotics, intestinal comorbidities, and even metabolic diseases may continously alter microbiota diversity and function. The study of vegan diet-microbiota interactions is a rapidly evolving field, since plenty of research has been focused on the potential effects of plant-based dietary patterns on the human gut microbiota. It has been reported that well-planned vegan diets and their associated components affect both the bacterial composition and metabolic pathways of gut microbiota. Certain benefits associated with medical disorders but also limitations (including nutritional deficiencies) have been documented. Although the vegan diet may be inadequate in calorific value, it is rich in dietary fiber, polyphenols, and antioxidant vitamins. The aim of the present study was to provide an update of the existing knowledge on nutritional status of vegan diets and the influence of their food components on the human gut microbiota and health.

Effects of rosuvastatin with or without ezetimibe on clinical outcomes in patients undergoing elective vascular surgery: results of a pilot study.

OBJECTIVE: Cardiovascular complications represent a major cause of morbidity and mortality in patients undergoing vascular surgery. This was a prospective randomized, open-label study to investigate the effect of lipid-lowering treatment by statin monotherapy or intensified by combining statin with ezetimibe on a  12-month  prognosis after vascular surgery. METHODS: Patients were randomly assigned to receive rosuvastatin (RSV) 10 mg/d or rosuvastatin 10 mg/d plus ezetemibe (RSV/EZT) 10 mg/d, starting prior to scheduled surgical procedure. The primary end point was the first major cardiovascular event, including death from cardiac causes, nonfatal myocardial infarction, ischemic stroke, and unstable angina. RESULTS: A total of 136 patients assigned to RSV and 126 to RSV/EZT completed the study protocol. As many as 6.6% of patients in the RSV group experience a major cardiovascular event within 30 days after surgery versus 5.6% in the RSV/EZT group (P = .72). From month 1 to 12 of the follow-up period, primary end point was observed (9 taking RSV vs 2 in the RSV/EZT group [P = .04]). Intensified lipid-lowering therapy with RSV/EZT was associated with a greater decrease in low-density lipoprotein cholesterol levels compared with RSV (75.87 ± 31.64 vs 87.19 ± 31.7, P = .004), while no differential effect on triglyceride, high-density lipoprotein cholesterol or high-sensitivity C-reactive protein levels was noted between groups. CONCLUSION: Our findings indicate that statin therapy intensified by ezetimibe may reduce the incidence of cardiovascular events within the first 12 months after vascular surgery. Nonetheless, whether the use of ezetimibe as an add-on therapy to reduce cardiovascular risk in these patients needs to be tested in larger future studies.

Combined 5' UTR RFLP analysis and VP1 sequencing for epidemic investigation of enteroviruses.

Enteroviruses, the main cause of aseptic meningitis, consist of 100 serotypes, and many of them have been associated with large outbreaks. In the present study, a comparison of RFLP analysis of the 5' untranslated region (5'UTR) and sequencing of both the 5'UTR and VP1 regions was conducted for epidemiological linkage of 27 clinical enterovirus strains. The clinical enterovirus strains were clustered into five restriction profile groups. Even though the restriction profile clusters of clinical isolates were not related to those of the respective prototype strains, epidemiological relationships between the members of each cluster were observed. The restriction profile clusters in the 5'UTR corresponded to the phylogenetic clusters in the VP1 genomic region. The incongruence between the topology of Gior strain in 5'UTR and VP1 phylogenetic trees indicates a recombination event. The proposed RFLP assay in combination with VP1 sequencing can offer crucial epidemiological information about the circulating enteroviruses.

Postoperative levels of cardiac troponin versus CK-MB and high-sensitivity C-reactive protein for the prediction of 1-year cardiovascular outcome in patients undergoing vascular surgery.

OBJECTIVE: This study evaluated comparatively the predictive value of postoperative cardiac troponin I (cTnI), creatinine kinase (CK)-MB, and high-sensitivity C-reactive protein (hs-CRP) in 1-year cardiovascular mortality and morbidity in patients undergoing elective vascular surgery. METHODS: A total of 295 consecutive patients undergoing elective noncardiac vascular surgery were prospectively followed-up over a period of 12 months. The levels of cTnI, CK-MB, and hs-CRP were measured preoperatively and 24 h after operation. The primary endpoint was the composite of cardiovascular death, nonfatal acute myocardial infarction, ischemic stroke, and unstable angina. RESULTS: The primary endpoints occurred in 11 patients (3.8%). Receiver operating characteristic curve analysis showed that postoperative cTnI was a strong predictor of a cardiovascular event during 1-year follow-up (area under the curve, 0.852; P<0.001). Areas under the curve for hs-CRP and for CK-MB were 0.734 (P=0.008) and 0.494 (P=0.947). A threshold cTnI value of 0.4 ng/ml was highly associated with the occurrence of a cardiovascular event, with a sensitivity of 80% and specificity of 81%. Furthermore, cTnI levels provided a significantly better prediction than CK-MB levels (P=0.009) and tended to be superior to hs-CRP (P=0.2). CONCLUSION: Postoperative cTnI levels seem to be superior to CK-MB and hs-CRP levels for the prediction of 1-year cardiovascular mortality and morbidity in patients undergoing elective vascular surgery.

Use of interferon-gamma release assay for latent tuberculosis infection screening in older adults exposed to tuberculosis in a nursing home.

OBJECTIVES: To assess the additive value of a newly marketed interferon-gamma release assay, QuantiFERON-TB Gold In-Tube (QFT-GIT), to a single tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) in older adults who have been exposed to TB in a nursing home. DESIGN: Contact tracing included clinical examination, chest radiography, TST, and QFT-GIT in TST-negative people (TST< 5 mm). SETTING: A private nursing home. PARTICIPANTS: Seventy-seven individuals (63 elderly residents, 14 young employees) who had been exposed to an active TB case in a private nursing home. MEASUREMENTS: Comparison of TST and QFT-GIT in older adults who have been exposed to TB. RESULTS: For the TST, the positive response rate was 31.7% (n=20) of elderly residents and 43% (n=6) of staff. Positive QFT-GIT results were obtained in seven (16.3%) elderly residents with negative TST, six of whom were aged 80 and older. QFT-GIT increased the percentage of possible LTBI in this group from 31.7% to 42.9%. CONCLUSION: QFT-GIT has a significant additive value to single TST for detecting LTBI in institutionalized older adults, identifying infected subjects anergic to the TST.

Usefulness of Herpes Consensus PCR methodology to routine diagnostic testing for herpesviruses infections in clinical specimens.

The purposes of the study were to assess the usefulness of simultaneously amplifying herpes simplex virus 1 and 2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus and human herpesvirus 6 DNA in various clinical specimens and to analyze clinical events in patients presenting positive results. A total of 763 clinical samples obtained from 758 patients, including 115 cerebrospinal fluids, 102 aqueous fluids, 445 swabs from genital (152), oro-facial (138) and other (155) skin lesions, 96 eye swabs and 5 bronchoalveolar lavages, were tested by using the Consensus polymerase chain reaction methodology. The clinical files of the patients were consulted retrospectively. 171 of the 758 patients (22.5%) were positive for at least one of the six target viruses: herpes simplex virus 1 (n = 95), varicella-zoster virus (n = 40), herpes simplex virus 2 (n = 21), herpes simplex virus 1 plus herpes simplex virus 2 (n = 8), cytomegalovirus (n = 4), Epstein-Barr virus (n = 1), human herpesvirus 6 (n = 1), and herpes simplex virus 1 plus human herpesvirus 6 (n = 1). The Consensus methodology enabled the rapid and accurate detection of herpesviruses in various clinical specimens and provided a reliable tool in the diagnosis of herpetic infections.