Increased T-Cell Activation and Th1 Cytokine Concentrations Prior to the Diagnosis of B-Cell Lymphoma in HIV Infected Patients

Background

Despite the use of combined antiretroviral therapy, HIV-infected individuals have a higher risk of developing B-cell lymphoma compared to the general population. We aim to explore whether lymphocyte activation, increase in Th1 response as well as markers of EBV reactivation, may precede lymphoma diagnosis.

Methods

Thirteen cases and 26 controls matched on CD4⁺ T-cell count and HIV plasma viral load were identified. Samples were collected 0 to 5 years prior to B-cell lymphoma diagnosis. Seven out of 13 (54 %) and 16/26 (61.5 %) of cases and controls were receiving antiretroviral therapy at the time of sampling, respectively. CD8⁺ T-cell activation and Th1 cytokine concentrations were measured before lymphoma onset, together with IgG antibodies directed against viral capsid antigen (VCA) and serum levels of EBV DNA.

Results

A higher level of CD8⁺ T-cell activation was observed in patients developing lymphoma. Four out of seven Th1 cytokine serum concentrations were significantly higher in patients with lymphoma than in the control group: IL-2R, IL-12p40/70, IFN-γ-inducible protein 10 (IP-10) and monokine induced by IFN-γ (MIG). Anti-VCA IgG level were significantly higher in cases than in controls. Four cases (30 %) but no controls had detectable EBV DNA in serum.

Conclusion

A higher level of T-cell activation, Th1 cytokine serum concentration and markers of EBV replication, preceded B-cell lymphoma diagnosis. This may suggest that viral antigen stimulation is associated with the genesis of lymphoma in HIV-infected patients.     

Stimulus transformation into motor action: Dynamic graph analysis reveals a posterior‐to‐anterior shift in brain network communication of older subjects

Cognitive performance slows down with increasing age. This includes cognitive processes that are essential for the performance of a motor act, such as the slowing down in response to an external stimulus. The objective of this study was to identify aging‐associated functional changes in the brain networks that are involved in the transformation of external stimuli into motor action. To investigate this topic, we employed dynamic graphs based on phase‐locking of Electroencephalography signals recorded from healthy younger and older subjects while performing a simple visually‐cued finger‐tapping task. The network analysis yielded specific age‐related network structures varying in time in the low frequencies (2–7 Hz), which are closely connected to stimulus processing, movement initiation and execution in both age groups. The networks in older subjects, however, contained several additional, particularly interhemispheric, connections and showed an overall increased coupling density. Cluster analyses revealed reduced variability of the subnetworks in older subjects, particularly during movement preparation. In younger subjects, occipital, parietal, sensorimotor and central regions were—temporally arranged in this order—heavily involved in hub nodes. Whereas in older subjects, a hub in frontal regions preceded the noticeably delayed occurrence of sensorimotor hubs, indicating different neural information processing in older subjects. All observed changes in brain network organization, which are based on neural synchronization in the low frequencies, provide a possible neural mechanism underlying previous fMRI data, which report an overactivation, especially in the prefrontal and pre‐motor areas, associated with a loss of hemispheric lateralization in older subjects.     

Education modifies the relation of vascular pathology to cognitive function: cognitive reserve in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

A clinical impact of cognitive reserve (CR) has been demonstrated in Alzheimer's disease, whereas its role in vascular cognitive impairment (VCI) is largely unknown. In this study, we investigated the impact of CR in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a genetic variant of pure VCI. A total of 247 NOTCH3 mutation carriers from a two-center study were investigated using detailed neuropsychological and neuroimaging protocols. CR was operationalized as years of formal education. Brain pathology was assessed by MRI using normalized brain volume and lacunar lesion volume as proxies. Multivariate analyses were done for each structural measure with scores of processing speed, executive function, and memory as dependent variables. Additional linear regression models were conducted with interaction terms for education × brain volume and education × lacunar lesion volume. Education had an independent impact on cognitive performance in subjects with mild and moderate degrees of brain pathology, whereas there was no significant influence of education on cognition in patients with severe MRI changes. This interaction was found for processing speed, the cognitive domain most impaired in our patients. Our findings demonstrate an interaction of education and brain pathology in regard to cognitive impairment: the effect of education seems most pronounced in early disease stages but may ultimately be overwhelmed by the pathological changes. The results extend the concept of CR to VCI.     

Mapping the microbiological diversity of odontogenic abscess: are we using the right drugs?

Objectives

The aim of this study was categorizing the microbial flora and susceptibility to antibiotics and to clarify to which degree the empiric administered antibiotics are suitable for therapy.

Materials and methods

A 3.5-year retrospective study evaluated hospital records of 206 patients who suffered from head and neck infections of odontogenic origin. All patients underwent surgical incision and drainage and received intravenous antibiotics and inpatient treatment. The specimens were obtained by performing a swab.

Results

Two hundred six patients were included with 251 strains isolated (1.22 per patient). One hundred eight strains showed antibiotic resistance. Eighty-seven patients showed at least one bacterial strain that showed antibiotic resistance (42.2%). The most frequent isolated bacteria were Streptococcus spp. (n = 116), with a high rate of antibiotic resistance (50.8%). We investigated 205 cases of antibiotic resistance in 87 subjects. Nine bacterial strains showed no susceptibility to unacid (4.3%) and 36 strains to clindamycin (17.5%).

Conclusion

Antibiotic resistance against clindamycin was rather high. The distribution of the afflicted spaces and isolated bacteria was alike recent findings. It is mandatory to understand that immediate surgical treatment in terms of incision and drainage is the basis in abscess treatment. Antibiotic treatment is adjunct therapy.

Clinical relevance

Streptococcus species were the most frequently identified bacteria presenting antibiotic resistance in more than 50%. Increased resistant rates for clindamycin require reconsiderations regarding an empiric antibiotic treatment.

     

Peri-implant bone preservation of a novel,self-cutting,and fully tapered implant in the healed crestal ridge of minipigs: submerged vs. transgingival healing

Clinical Oral Investigations - The aim of this study was to assess the influence of transgingival compared with submerged healing on peri-implant bone maintenance around a novel, fully tapered...     

The sandwich osteotomy technique to treat vertical alveolar bone defects prior to implant placement: a systematic review

Clinical Oral Investigations - The aim of this systematic review was to investigate the predictability of the sandwich osteotomy technique to provide sufficient alveolar bone height for dental...     

Sex-specific Differences of the Infraacetabular Corridor: A Biomorphometric CT-based Analysis on a Database of 523 Pelves

BackgroundAn infraacetabular screw path facilitates the closure of a periacetabular fixation frame to increase the plate fixation strength in acetabular fractures up to 50%. Knowledge of the variance in corridor sizes and axes has substantial surgical relevance for safe screw placement.Questions/purposes(1) What proportion of healthy pelvis specimens have an infraacetabular corridor that is 5 mm or larger in diameter? (2) Does a universal corridor axis and specific screw entry point exist? (3) Are there sex-specific differences in the infraacetabular corridor size or axis and are these correlated with anthropometric parameters like age, body weight and height, or the acetabular diameter?MethodsA template pelvis with a mean shape from 523 segmented pelvis specimens was generated using a CT-based advanced image analyzing system. Each individual pelvis was registered to the template using a free-form registration algorithm. Feasible surface regions for the entry and exit points of the infraacetabular corridor were marked on the template and automatically mapped to the individual samples to perform a measurement of the maximum sizes and axes of the infraacetabular corridor on each specimen. A minimum corridor diameter of at least 5 mm was defined as a cutoff for placing a 3.5-mm cortical screw in clinical settings.ResultsIn 484 of 523 pelves (93%), an infraacetabular corridor with a diameter of at least 5 mm was found. Using the mean axis angulations (54.8° [95% confidence interval {CI}, 0.6] from anterocranial to posterocaudal in relation to the anterior pelvic plane and 1.5° [95% CI, 0.4] from anteromedial to posterolateral in relation to the sagittal midline plane), a sufficient osseous corridor was present in 64% of pelves. Allowing adjustment of the three-dimensional axis by another 5° included an additional 25% of pelves. All corridor parameters were different between females and males (corridor diameter, 6.9 [95% CI, 0.2] versus 7.7 [95% CI, 0.2] mm; p < 0.001; corridor length, 96.2 [95% CI, 0.7] versus 106.4 [95% CI, 0.6] mm; p < 0.001; anterior pelvic plane angle, 54.0° [95% CI, 0.9] versus 55.3° [95% CI, 0.8]; p < 0.01; sagittal midline plane angle, 4.3° [95% CI, 0.6] versus −0.3° [95% CI, 0.5]; p < 0.001).ConclusionThis study provided reference values for placement of a 3.5-mm cortical screw in the infraacetabular osseous corridor in 90% of female and 94% of male pelves. Based on the sex-related differences in corridor axes, the mean screw trajectory is approximately parallel to the sagittal midline plane in males but has to be tilted from medial to lateral in females. Considering the narrow corridor diameters, we suggest an individual preoperative CT scan analysis for fine adjustments in each patient.