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Background and purpose: To assess the clinical spectrum of central nervous system (CNS) involvement as well as cerebrospinal fluid (CSF) and neuroimaging findings in patients with Whipple's disease (WD) and to analyze the association of neurological symptoms with CSF and imaging findings. Methods: Neurological involvement was retrospectively analyzed in a series of 36 patients diagnosed with WD at a single center between 1992 and 2019. Findings of 81 comprehensive CSF examinations from 36 patients, including polymerase chain reaction (PCR) tests for Tropheryma whipplei (TW) in CSF from 35 patients, were systematically evaluated. The prevalence of ischemic stroke in patients with WD was compared to a matched control cohort. Results: Neurological symptoms occurred in 23 of 36 (63.9%) patients, with cognitive, motor, and oculomotor dysfunction being most frequent. TW was detected by PCR in CSF of 13 of 22 (59.1%) patients with and four of 13 (30.8%, p = 0.0496) patients without neurological symptoms. Total CSF protein (p = 0.044) and lactate (p = 0.035) were moderately elevated in WD with neurologic symptoms compared with WD without. No intrathecal immunoglobulin synthesis was observed. Three of 36 (8.3%) patients had hydrocephalus due to aqueductal stenosis. Patients with WD had an unexpectedly high prevalence of ischemic stroke (10/36, 27.7%) compared to matched controls (10/360, 3.2%). Conclusions: Neurological involvement in patients with WD is common. Detection of TW DNA in CSF is only partly associated with neurological symptoms. Elevated CSF parameters suggest CNS parenchymal infection. Stroke is a hitherto underrecognized manifestation of WD. These findings suggest that mechanisms beyond CNS infection contribute to the spectrum of CNS involvement in WD. [ABSTRACT FROM AUTHOR]

Orthopedic device‐related infection (ODRI), including both fracture‐related infection (FRI) and periprosthetic joint infection (PJI), remain among the most challenging complications in orthopedic and musculoskeletal trauma surgery. ODRI has been convincingly shown to delay healing, worsen functional outcome and incur significant socio‐economic costs. To address this clinical problem, ever more sophisticated technologies targeting the prevention and/or treatment of ODRI are being developed and tested in vitro and in vivo. Among the most commonly described innovations are antimicrobial‐coated orthopedic devices, antimicrobial‐loaded bone cements and void fillers, and dual osteo‐inductive/antimicrobial biomaterials. Unfortunately, translation of these technologies to the clinic has been limited, at least partially due to the challenging and still evolving regulatory environment for antimicrobial drug‐device combination products, and a lack of clarity in the burden of proof required in preclinical studies. Preclinical in vivo testing (i.e. animal studies) represents a critical phase of the multidisciplinary effort to design, produce and reliably test both safety and efficacy of any new antimicrobial device. Nonetheless, current in vivo testing protocols, procedures, models, and assessments are highly disparate, irregularly conducted and reported, and without standardization and validation. The purpose of the present opinion piece is to discuss best practices in preclinical in vivo testing of antimicrobial interventions targeting ODRI. By sharing these experience‐driven views, we aim to aid others in conducting such studies both for fundamental biomedical research, but also for regulatory and clinical evaluation. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:271–287, 2019. [ABSTRACT FROM AUTHOR]

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Medical device-related infections cause undue patient distress, increased morbidity and mortality and pose a huge financial burden on healthcare services. The pathogens are frequently distributed heterogeneously in biofilms, which can persist without being effectively cleared by host immune defenses and antibiotic therapy. At present, there is no 'gold standard' available to reveal the presence of device-related biofilm infections. However, adequate sample collection and logistics, standardised diagnostic methods, and interpretation of results by experienced personnel are important steps in efficient diagnosis and treatment of these infections. The focus of this mini review is on prosthethic joint and cardiovascular implantable device infections, which exemplify permanent devices that are placed in a sterile body site. These device-related infections represent some of the most challenging in terms of both diagnosis and treatment. [ABSTRACT FROM AUTHOR]

The article discusses the microbial ecology, behavior, and conflicts of biofilms. It says that the mouth provides the habitat and supports the growth of microorganisms, which can be analyzed through different approaches such as fluorescence in situ hybridization and gene amplification. It states that changes in the host environment bear consequences that disrupt the normal balance of microflora and cause diseases. It adds that cell-cell communication can control dental plaque biofilm.

Drescher J, Schlafer S, Schaudinn C, Riep B, Neumann K, Friedmann A, Petrich A, Göbel UB, Moter A. Molecular epidemiology and spatial distribution of Selenomonas spp. in subgingival biofilms. Eur J Oral Sci 2010; 118: 466–474. © 2010 Eur J Oral Sci The aetiology of periodontal disease has been a field of intensive research in the past decades. Along with a variety of other putative pathogens, different members of the genus Selenomonas have repeatedly been associated with both generalized aggressive periodontitis and chronic periodontitis. For the present study, a specific oligonucleotide probe targeting the majority of all oral Selenomonas spp. was designed. Their prevalence was determined, using dot-blot hybridization, in a total of 742 subgingival samples collected from patients with generalized aggressive ( n = 62) and chronic periodontitis ( n = 82), and from periodontitis-resistant subjects ( n = 19). In addition, fluorescence in situ hybridization (FISH) and electron microscopy were performed to analyze the spatial arrangement of Selenomonas in subgingival biofilms collected from patients with generalized aggressive periodontitis. In the samples from patients, Selenomonas spp. showed a lower prevalence in both diseased groups compared with other putative pathogens, and a relatively high prevalence in the periodontitis-resistant group. Consequently, Selenomonas spp. do not seem to be suitable diagnostic marker organisms for periodontal disease. By contrast, FISH and electron microscopic analysis of periodontal carriers revealed that Selenomonas spp. appeared in large numbers in all parts of the collected biofilms and seemed, if present in a site from patients, to make a relevant contribution to their structural organization. [ABSTRACT FROM AUTHOR]

Background: This study assessed the long-term effects of adjunctive antimicrobial therapy on periodontal disease progression and oral colonization. Methods: Patients with previously untreated chronic periodontitis and subgingival Actinobacillus actinomycetemcomitans and/or Porphyromonas gingivalis were randomly assigned to subgingival scaling without (control group) or with systemic amoxicillin plus metronidazole and CHX irrigation (test group). Relative attachment levels were determined and subgingival and mucosal plaque samples were taken at baseline, at 10 days (plaque only) and at 3, 6, 9, 12, 18, and 24 months following initial therapy. During maintenance therapy, patients received supragingival debridement only. Results: After 24 months, the 18 test group patients showed at sites with initial probing depths (PD) ≥7 mm a significantly (P <6.05) higher frequency of 2 mm or more attachment gain (37.3% ± 4.6%) and lower frequency of attachment loss (7.2% ± 3.1%) compared to the 17 controls (8.2% ± 3.9% and 19.1% ± 13.1%, respectively). Compared to controls, the intraoral prevalence of A. actinomycetemcomitans (up to 16 months) and P. gingivalis (up to 3 months) decreased and that of Eikenella corrodens (at 10 days) increased in test patients (P<0.05). In both treatment groups, the detection frequency of Tannerella forsythensis decreased transiently, while an overall increase was recorded for Treponema ssp. Conclusions: Over the 24-month period, a single course of the administered adjunctive antimicrobial therapy led to a relative risk reduction of 62% for attachment loss at deep sites. However, with the exception of A. actinomycetemcomitans, it failed to induce long-term changes in the prevalence profiles of oral colonization. [ABSTRACT FROM AUTHOR]

Schweickert B, Moter A, Lefmann M, Göbel UB. Let them fly or light them up: matrix-assisted laser desorption/Ionization time of flight (MALDI-TOF) mass spectrometry and fluorescencein situhybridization (FISH). APMIS 2004;112:856–85.This review focuses on clinical bacteriology and by and large does not cover the detection of fungi, viruses or parasites. It discusses two completely different but complementary approaches that may either supplement or replace classic culture-based bacteriology. The latter view may appear provocative in the light of the actual market penetration of molecular genetic testing in clinical bacteriology. Despite its elegance, high specificity and sensitivity, molecular genetic diagnostics has not yet reached the majority of clinical laboratories. The reasons for this are manifold: Many microbiologists and medical technologists are more familiar with classical microbiological methods than with molecular biology techniques. Culture-based methods still represent the work horse of everyday routine. The number of available FDA-approved molecular genetic tests is limited and external quality control is still under development. Finally, it appears difficult to incorporate genetic testing in the routine laboratory setting due to the limited number of samples received or the lack of appropriate resources. However, financial and time constraints, particularly in hospitals as a consequence of budget cuts and reduced length of stay, lead to a demand for significantly shorter turnaround times that cannot be met by culture-dependent diagnosis. As a consequence, smaller laboratories that do not have the technical and personal equipment required for molecular genetic amplification techniques may adopt alternative methods such as fluorescencein situhybridization (FISH) that combines easy-to-perform molecular hybridization with microscopy, a technique familiar to every microbiologist. FISH is hence one of the technologies presented here. For large hospital or reference laboratories with a high sample volume requiring massive parallel high-throughput testing we discuss matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF) of nucleic acids, a technology that has evolved from the post-genome sequencing era, for high-throughput sequence variation analysis (1, 2). [ABSTRACT FROM AUTHOR]