The Unique Clinical Features and Outcome of Infectious Endocarditis and Vertebral Osteomyelitis Co-infection

Objective

The clinical significance of vertebral osteomyelitis and infectious endocarditis co-infection is unclear. This study investigates the rate, clinical features, and outcome of vertebral osteomyelitis with and without concomitant infectious endocarditis.

Methods

A retrospective study of all cases of osteomyelitis with spinal imaging (n = 176), from January 2007 to April 2013, that were diagnosed as vertebral osteomyelitis. Sixty-two patients with spontaneous vertebral osteomyelitis were identified after excluding postsurgical, decubitus ulcers and spinal metastases. Seventeen (27%) were identified with concomitant infectious endocarditis.

Results

All patients presented with back pain and 59% were diagnosed with infectious endocarditis subsequent to vertebral osteomyelitis. Distinguishing features among the co-infection group include the increased use of transesophageal echocardiography (94% vs 58%, P = .004), predisposing cardiac conditions (59% vs 16%, P = .001), and Gram-positive bacteremia, of which Streptococcus sp. and Enterococcus sp. were more common (35% vs 11%, P = .026). Adverse neurologic events were increased significantly in the co-infection group (59% vs 22%, P = .006). On transesophageal echocardiography, 88% of co-infection patients had highly mobile vegetations, 9 of which measured 10 mm or more. The overall mortality was 41% and 29% in the co-infection and lone vertebral osteomyelitis groups, respectively (P = .356). One-year mortality was identical for both groups at 24% (P = .999), and higher than previously reported (11.3% for lone vertebral osteomyelitis).

Conclusions

Patients with vertebral osteomyelitis, in whom infectious endocarditis is not excluded, are at increased risk for adverse neurologic events and mortality. The prompt diagnosis of infectious endocarditis, and associated high-risk features that may benefit from surgical intervention, require early evaluation by transesophageal echocardiography.     

Unenhanced spiral CT for the assessment of renal colic. How does limiting the referral base affect the discovery of additional findings not related to urinary tract calculi?

The value of unenhanced spiral CT (UESCT) for investigating acute flank pain suggestive of urinary tract calculi is increasingly appreciated in the last few years. Recent studies have identified the advantages of UESCT in recognizing alternative findings within or outside the urinary tract. We sought to determine how narrowing the referral base for the UESCT would affect the discovery of potentially significant alternative findings in patients with acute flank pain suggestive of renal colic. Between January 1999 and December 1999, 425 patients, 271 (63.8%) men and 154 (36.2%) women who were 1-90 years old (mean 45.7 years old) with acute flank pain were studied with UESCT. CT studies were solely ordered by urologists, and only patients with intractable renal colic or patients that returned more than once to the emergency room with the complaint of acute flank pain were studied. A calculus within the ureter was diagnostic of an obstructive stone. Any other abnormality within the abdomen and pelvis was reported. A ureteral calculus was detected on 251 (59%) CT scans. Nineteen (4.5%) CT scans were consistent with recent excretion of a stone. In 112 (26.3%) CT scans, the cause for the patient's acute flank pain could not be explained. Forty-three (10.1%) alternative significant diagnoses that explain the patient's complaints were found. Nineteen (44%) were findings related to the urinary tract, and 24 (56%) were not related to the urinary tract. Ninety-seven (22.3%) additional findings not significant to the patient's current complaint were also reported. Even when narrowing the indications for the UESCT, about 10% of significant alternative findings to urinary stones were encountered. The variety of diagnoses found unexpectedly on the UESCT that alter a patient's management demonstrates the pivotal role of UESCT in triaging these patients rapidly towards optimal therapy. The UESCT can be used as a useful screening tool, sometimes revealing the exact pathology and sometimes directing the radiologist to the modality by which to continue.     

Pelvic enthesopathy on CT is significantly more prevalent in patients with diffuse idiopathic skeletal hyperostosis (DISH) compared with matched control patients

Clinical Rheumatology - The purpose of this study is to evaluate the prevalence of pelvic enthesopathy on computed tomography (CT) in patients with DISH compared to matched control group. Pelvic CT...     

In vivo toxicity studies of europium hydroxide nanorods in mice

Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence and pro-angiogenic properties to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [Eu^III(OH)₃] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mg kg^− 1 day^− 1) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice euthanized on days 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod-treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods.     

The role of unenhanced helical CT in the evaluation of suspected renal colic and atypical abdominal pain in children

BACKGROUND: Urolithiasis in children has a different pattern of presentation than in adults and its incidence is lower. Unenhanced helical CT (UEHCT) for suspected urinary tract calculi in adults has high sensitivity and specificity for detecting even minute calculi. UEHCT has been proposed as a fast and sensitive method for identifying urinary stones in children. However, to our knowledge, the role of UEHCT and its value in the diagnostic work-up of urinary stones in children has not been studied. OBJECTIVE: To evaluate the significance of UEHCT as a diagnostic tool for urinary stones in children. MATERIALS AND METHODS: We retrospectively analysed data on 20 children who underwent UEHCT during 1999-2000. RESULTS: Findings on UEHCT were significant in establishing a diagnosis in only seven patients and only three were shown to have urinary stones. Only one significant finding was found in the group who underwent UEHCT without prior US. US performed prior to UEHCT was a significant screening tool, and when results were equivocal, UEHCT further helped in establishing diagnosis. CONCLUSIONS: We propose that US be the first imaging modality in children with suspected urolithiasis. When the result of this examination is uncertain or abnormal, UEHCT will probably add further information which will contribute to the diagnosis.     

Broad ligament hematoma following a normal vaginal delivery

Broad ligament hematoma is an unusual complication that can occur during delivery, just after delivery or later in the puerperium. Rapid labor, cesarean section, instrumental deliveries, and trauma have been suggested as predisposing factors. A case of a broad ligament hematoma developing after normal vaginal delivery is presented. A high level of suspicion and the use of imaging modalities such as trans-vaginal ultrasound and computerized tomography confirmed the diagnosis. Conservative management was employed due to the patient’s hemodynamic stability.     

A central role for Necl4 (SynCAM4) in Schwann cell-axon interaction and myelination

Myelination in the peripheral nervous system requires close contact between Schwann cells and the axon, but the underlying molecular basis remains largely unknown. Here we show that cell adhesion molecules (CAMs) of the nectin-like (Necl, also known as SynCAM or Cadm) family mediate Schwann cell-axon interaction during myelination. Necl4 is the main Necl expressed by myelinating Schwann cells and is located along the internodes in direct apposition to Necl1, which is localized on axons. Necl4 serves as the glial binding partner for axonal Necl1, and the interaction between these two CAMs mediates Schwann cell adhesion. The disruption of the interaction between Necl1 and Necl4 by their soluble extracellular domains, or the expression of a dominant-negative Necl4 in Schwann cells, inhibits myelination. These results suggest that Necl proteins are important for mediating axon-glia contact during myelination in peripheral nerves.     

Magnetic resonance imaging of hindfoot involvement in patients with spondyloarthritides: comparison of low-field and high-field strength units

OBJECTIVE: To compare MRI evaluation of a painful hindfoot of patients with spondyloarthritides (SpA) on low-field (0.2 T) versus high-field (1.5 T) MRI. MATERIALS AND METHODS: Patients with SpA and hindfoot pain were randomly referred to either high-field or low-field MRI. Twenty-seven patients were evaluated (male/female: 17:10; mean age: 39+/-1.4 years). Fifteen patients were examined by low-field and 12 by high-field MRI. Two patients (evaluated by high-field MRI) were excluded. Images were separately read by two radiologists who later reached a consensus. In each patient the prevalence of erosions, fluid, synovitis or bone marrow edema of the hindfoot joints, tendinosis or tenosynovitis of tendons, enthesitis of the plantar fascia and Achilles tendon and retrocalcaneal bursitis were recorded. Clinical and demographic parameters were comparable between both groups. RESULTS: MRI evaluation of joints and tendons of the hindfoot revealed no significant differences in patients with SpA groups for all parameters. Analyzing all joints or tendons together, there was no statistically significant difference between the two groups. CONCLUSION: Low-field and high-field MRI provide comparable information for evaluation of inflammatory hindfoot involvement. Thus, low-field MRI can be considered as a reliable diagnostic tool for the detection of hindfoot abnormalities in SpA patients.     

Patient-Derived Anti-NMDAR Antibody Disinhibits Cortical Neuronal Networks through Dysfunction of Inhibitory Neuron Output

Anti-NMDA receptor (NMDAR) encephalitis is a severe neuropsychiatric disorder associated with autoantibodies against NMDARs, which cause a variety of symptoms from prominent psychiatric and cognitive manifestations to seizures and autonomic instability. Previous studies mainly focused on hippocampal effects of these autoantibodies, helping to explain mechanistic causes for cognitive impairment. However, antibodies'' effects on higher cortical network function, where they could contribute to psychosis and/or seizures, have not been explored in detail until now. Here, we employed a patient-derived monoclonal antibody targeting the NR1 subunit of NMDAR and tested its effects on in vitro cultures of rodent cortical neurons, using imaging and electrophysiological techniques. We report that this hNR1 antibody drives cortical networks to a hyperexcitable state and disrupts mechanisms stabilizing network activity such as Npas4 signaling. Network hyperactivity is in part a result of a reduced synaptic output of inhibitory neurons, as indicated by a decreased inhibitory drive and levels of presynaptic inhibitory proteins, specifically in inhibitory-to-excitatory neuron synapses. Importantly, on a single-cell level hNR1 antibody selectively impairs NMDAR-mediated currents and synaptic transmission of cortical inhibitory neurons, yet has no effect on excitatory neurons, which contrasts with its effects on hippocampal neurons. Together, these findings provide a novel, cortex-specific mechanism of antibody-induced neuronal hyperexcitability, highlighting regional specificity underlying the pathology of autoimmune encephalitis.SIGNIFICANCE STATEMENT It is increasingly appreciated that the inadvertent activation of the immune system within CNS can underlie pathogenesis of neuropsychiatric disorders. Although the exact mechanisms remain elusive, autoantibodies derived from patients with autoimmune encephalitis pose a unique tool to study pathogenesis of neuropsychiatric states. Our analysis reveals that autoantibody against the NMDA receptor (NMDAR) has a distinct mechanism of action in the cortex, where it impairs function of inhibitory neurons leading to increased cortical network excitability, in contrast to previously described hippocampal synaptic mechanisms of information encoding, highlighting brain regional specificity. Notably, similar mechanism of NMDAR-mediated inhibitory hypofunction leading to cortical disinhibition has been suggested to underlie pathology of schizophrenia, hence our data provide new evidence for common mechanisms underlying neuropsychiatric disorders.