Pneumococcal sepsis and meningitis in vaccinated subjects: a review of 55 reported cases

Fifty-five cases of the occurrence of serious pneumococcal infections in both splenectomized and nonsplenectomized individuals who received pneumococcal vaccine were reviewed from the literature. Reasons for vaccine failure included the occurrence of non-vaccine-type pneumococcal infections (18 cases), possible poor antibody response to the vaccine, especially if it is given postsplenectomy and/or following intensive steroid or other immunosuppressive therapy, and decline in antibody titer over time. Although the total number of vaccinated individuals is unknown, the overwhelming majority of the many thousands of vaccinees have been successfully protected with pneumococcal vaccine. In spite of very rare vaccine failures, pneumococcal vaccination (and perhaps penicillin prophylaxis) is strongly recommended for patients at high risk of developing serious pneumococcal infections, including all individuals undergoing splenectomy for any reason, or for those who have had a splenectomy or have functional asplenia.     

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

ObjectiveInterleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc).Subjects and MethodsA total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA.ResultsLevels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls.ConclusionThe higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.     

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.     

Lack of association between hyperprolactinemia and colon carcinoma

Two recent studies reported that many patients with colorectal carcinoma have elevated serum prolactin (PRL) concentrations and have suggested ectopic PRL secretion as the cause. In the present study, serum PRL was minimally elevated in 16 of 116 colon cancer patients and 2 of 25 control subjects; medications or chemotherapy appeared to be responsible for the PRL elevations in 11 of 16 cancer patients. Serum PRL was not correlated with either plasma carcinoembryonic antigen or disease stage. Preoperative and postoperative serum PRL concentrations were similar in 26 evaluated patients. None of 19 colorectal tumors was positive for PRL staining by immunohistochemistry. Thus, we could not confirm previous reports of frequent hyperprolactinemia in patients with colorectal cancer; factors such as medications, anxiety, pain, and nausea may have raised serum PRL in these earlier studies. Serum PRL is not a useful marker for colon carcinoma, at least in patients in the United States.     

Type IV collagenase/gelatinase (MMP-2) is not increased in plasma of patients with cancer.

We have developed a sensitive and specific sandwich-type enzyme-linked immunosorbent assay to detect M(r) 72,000 type IV collagenase [matrix metalloproteinase 2 (MMP-2)] in human plasma. As a result of the linkage between MMP-2 production by cancer cells and the metastatic phenotype, we undertook this study to compare plasma MMP-2 levels in healthy individuals, patients with various types of cancer, and hospitalized patients with chronic diseases other than cancer. The results demonstrate that MMP-2 levels are not increased in cancer patients regardless of the extent of disseminated malignancy. In an effort to explain this data, we compared MMP-2 secretion by human umbilical vein endothelial cells and lung cancer cells passaged as cell lines. Endothelial cells secreted higher levels of MMP-2 than did lung cancer cells propagated in vitro. We propose that blood vessel lining cells make a sizable contribution to plasma levels of MMP-2 and may thereby obfuscate the detection of increased levels of MMP-2 originating from extravascular sources such as solid tumors.     

Three-dimensional isotropic wavelets for post-acquisitional extraction of latent images of atherosclerotic plaque components from micro-computed tomography of human coronary arteries

RATIONALE AND OBJECTIVES: The capability of wavelet transforms to separate signals into frequency bands is the basis for its use in image compression and storage, data management and transmission, and, recently, extraction of latent images of tissue components from noisy medical images. Analysis of temporal variations of radiofrequency backscatter of intravascular ultrasound with one-dimensional wavelets can detect lipid-laden plaque in coronary arteries with a sensitivity and specificity of >80%. In this study we evaluate the capability of a novel, 3-dimensional isotropic wavelet analysis to perform high resolution, non-directionally biased, statistically reliable, non-invasive discrimination between components of human coronary atherosclerotic plaques in micro-CT. MATERIALS AND METHODS: Coronary artery segments (5-15 mm) were excised at necropsy from 18 individuals with advanced coronary atherosclerosis. Specimens were imaged using a GE Locus SP ex vivo micro-CT scanner and processed for histological correlation (833 sections). The isotropic wavelet constructs were applied to the entire volume of CT data of each arterial segment to distinguish tissue textures of varying scales and intensities. Voxels were classified and plaque characterization achieved by comparing the relative magnitudes of these wavelet constituents to that of several reference plaque tissue components. RESULTS: Processing of micro-CT images via these isotropic wavelet algorithms permitted 3-D, color-coded, high resolution, digital discrimination between lumen, calcific deposits, lipid-rich deposits, and fibromuscular tissue providing detail not possible with conventional thresholding based on Hounsfield intensity units. Using the isotropic wavelets (with histology as the gold standard), lipid-rich pools approaching the size of the filter for the isotropic wavelet algorithm (0.25 mm [250 microns] in length) were identified with 81% sensitivity and 86% specificity. Calcific deposits, fibromuscular tissue, and lumen equal to or larger than the wavelet filter size were detected without error (100% sensitivity and specificity). CONCLUSION: Isotropic wavelet analysis permits high resolution, multi-dimensional identification of coronary atherosclerotic plaque components in micro-CT with sensitivity and specificity similar to that achieved with data obtained invasively (from IVUS in vivo) using one-dimensional wavelets. Further studies are necessary to test the applicability of this technology to clinical, multi-detector scanners.