Microfibrillar cardiomyopathy: a rare case

Microfibrillar cardiomyopathy is a very rare cause of restrictive cardiomyopathy (RCM). The index case was a male patient who presented with shortness of breath and pedal edema. Further clinical investigations favored a clinical diagnosis of RCM. An endomyocardial biopsy revealed subendocardial and interstitial hyaline eosinophilic material resembling amyloid that did not stain with Congo red. An electron microscopic examination showed that this material was composed of twisted linear and bundles of tangled microfibrils. The etiology of the microfibrillar deposition is currently unknown. The pathologists should entertain the diagnosis of microfibrillar cardiomyopathy in suspected cases of amyloidosis that are negative for Congo red.     

Cefpodoxime 10 μg disc screening test for detection of Neisseria gonorrhoeae with mosaic PBP2 and decreased susceptibility to extended-spectrum cephalosporins for public health purposes

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae remains a global public health problem. Susceptibility to first-line treatment extended-spectrum cephalosporins (ESCs) is decreasing worldwide resulting in therapeutic failures with oral ESCs. This study describes a cefpodoxime 10 μg disc test for screening for gonococci containing a penA mosaic allele encoding a mosaic penicillin-binding protein 2 (PBP2) and decreased ESC susceptibility. Selected clinical gonococcal isolates (n = 315), containing a high proportion of gonococci with decreased ESC susceptibility and high geographical, temporal and genetic diversity, were examined using agar dilution (n = 149; cefpodoxime and ceftriaxone) and Etest (n = 315; cefixime), and disc diffusion using a commercially available cefpodoxime 10 μg disc (n = 315). penA sequencing was performed on all isolates. The 2008 WHO gonococcal reference strains (n = 8) were included as quality controls. Using a ≤11 mm annular radius of growth inhibition as the breakpoint for the cefpodoxime 10 μg disc, all 78, with exception of one isolate (13 mm), mosaic PBP2-containing isolates, which also displayed decreased susceptibility to oral ESCs, were identified. In addition, 85 non-mosaic PBP2-containing isolates (44% of which contained a PBP2 A501 alteration) had annular radii ≤11 mm and raised minimal inhibitory concentrations to the ESCs. Screening for detection of mosaic PBP2-containing gonococci and decreased ESC susceptibility, most pronounced to oral ESCs, using a commercially available cefpodoxime 10 μg disc was rapid, inexpensive and sensitive. This test can be used in AMR surveillance programmes for public health purposes especially in less-resourced settings. Further studies to refine this disc testing-based approach are in progress.     

Activation of subthalamic neurons by contralateral subthalamic deep brain stimulation in Parkinson disease

Multiple studies have shown bilateral improvement in motor symptoms in Parkinson disease (PD) following unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal segment of the globus pallidus, yet the mechanism(s) underlying this phenomenon are poorly understood. We hypothesized that STN neuronal activity is altered by contralateral STN DBS. This hypothesis was tested intraoperatively in humans with advanced PD using microelectrode recordings of the STN during contralateral STN DBS. We demonstrate alterations in the discharge pattern of STN neurons in response to contralateral STN DBS including short latency, temporally precise, stimulation frequency-independent responses consistent with antidromic activation. Furthermore, the total discharge frequency during contralateral high frequency stimulation (160 Hz) was greater than during low frequency stimulation (30 Hz) and the resting state. These findings demonstrate complex responses to DBS and imply that output activation throughout the basal ganglia-thalamic-cortical network rather than local inhibition is a therapeutic mechanism of DBS.     

“Pathologic” fractures: should these be included in epidemiologic studies of osteoporotic fractures?

Summary

Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy.

Introduction

Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined “pathologic” fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy.

Methods

We studied US Medicare beneficiaries age ≥65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture.

Results

We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a “pathologic” vertebral fracture ICD-9 code, but 66% of persons with a “pathologic” hip fracture, there was evidence of a possible cancer diagnosis.

Conclusion

Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.