Impact of Vessel Suppressed-CT on Diagnostic Accuracy in Detection of Pulmonary Metastasis and Reading Time.

RATIONALE AND OBJECTIVES: To assess if vessel suppression (VS) improves nodule detection rate, interreader agreement, and reduces reading time in oncologic chest computed tomography (CT). MATERIAL AND METHODS: One-hundred consecutive oncologic patients (65 male; median age 60y) who underwent contrast-enhanced chest CT were retrospectively included. For all exams, additional VS series (ClearRead CT, Riverrain Technologies, Miamisburg) were reconstructed. Two groups of three radiologists each with matched experience were defined. Each group evaluated the SD-CT as well as VS-CT. Each reader marked the presence, size, and position of pulmonary nodules and documented reading time. In addition, for the VS-CT the presence of false positive nodules had to be stated. Cohen's Kappa (k) was used to calculate the interreader-agreement between groups. Reading time was compared using paired t test. RESULTS: Nodule detection rate was significantly higher in VS-CT compared to the SD-CT (+21%; p <0.001). Interreader-agreement was higher in the VS-CT (k = 0.431, moderate agreement) compared to SD-CT (k = 0.209, fair agreement). Almost all VS-CT series had false positive findings (97-99 out of 100). Average reading time was significantly shorter in the VS-CT compared to the SD-CT (154 ± 134vs. 194 ± 126; 21%, p<0.001). CONCLUSIONS: Vessel suppression increases nodule detection rate, improves interreader agreement, and reduces reading time in chest CT of oncologic patients. Due to false positive results a consensus reading with the SD-CT is essential.

Mitral annular calcification in the elderly - Quantitative assessment.

PURPOSE: To determine the reliability of subjective and objective quantification of mitral annular calcification (MAC) in elderly patients with severe aortic stenosis, to define quantitative sex- and age-related reference values of MAC, and to correlate quantitative MAC with mitral valve disease. METHODS: In this retrospective, IRB-approved study, we included 559 patients (268 females, median age 81 years, inter-quartile range 77-85 years) with severe aortic stenosis undergoing CT. Four independent readers performed subjective MAC categorization as follows: no, mild, moderate, and severe MAC. Two independent readers performed quantitative evaluation of MAC using the Agatston score method (AgatstonMAC). Mitral valve disease was determined by echocardiography. RESULTS: Subjective MAC categorization showed high inter-reader agreement for no (k â€‹= â€‹0.88) and severe MAC (k â€‹= â€‹0.75), whereas agreement for moderate (k â€‹= â€‹0.59) and mild (k â€‹= â€‹0.45) MAC was moderate. Intra-reader agreement for subjective MAC categorization was substantial (k â€‹= â€‹0.69 and 0.62). Inter- and intra-reader agreement for AgatstonMAC were excellent (ICC â€‹= â€‹0.998 and 0.999, respectively), with minor inconsistencies in MAC involving the left ventricular outflow tract/aortic valve. There were significantly more women than men with MAC (n â€‹= â€‹227, 85% versus n â€‹= â€‹209, 72%; p â€‹< â€‹0.001), with a significantly higher AgatstonMAC (median 597, range 81-2055 versus median 244; range 0-1565; p â€‹< â€‹0.001), particularly in patients ≥85 years of age. AgatstonMAC showed an area-under-the-curve of 0.84 to diagnose mitral stenosis, whereas there was no association of AgatstonMAC with mitral regurgitation (p â€‹> â€‹0.05). CONCLUSIONS: Our study in elderly patients with severe aortic stenosis shows that quantitative MAC scoring is more reliable than subjective MAC assessment. Women show higher AgatstonMAC scores than men, particularly in the elderly population. AgatstonMAC shows high accuracy to diagnose mitral stenosis.

Reproducibility of aortic valve calcification scoring with computed tomography - An interplatform analysis.

BACKGROUND: To investigate whether aortic valve calcification (AVC) scoring performed with different workstation platforms generates comparable and thus software-independent results. METHODS: In this IRB-approved retrospective study, we included 100 consecutive patients with symptomatic aortic stenosis undergoing CT prior to transcatheter aortic valve implantation. Two independent observers performed AVC scoring on non-enhanced images with commercially available software platforms of four vendors (GE, Philips, Siemens, 3mensio). Gender-specific Agatston score cut-off values were applied according to current recommendations to assign patients to different likelihood categories of aortic stenosis (unlikely to very likely). Comparative analysis of Agatston scores between the four platforms were performed by using Kruskal-Wallis analysis, Spearman rank correlation, linear regression analysis, and Bland-Altman analysis. Differences in category assignment were compared using Fisher's exact test and Cohen's kappa. RESULTS: For both observers, each workstation platform produced slightly different numeric AVC Agatston scores, however, without statistical significance (p = 0.96 and p = 0.98). Excellent correlation was found between platforms, with r = 0.991-0.996 (Spearman) and r2 = 0.981-0.992 (regression analysis) for both observers. Bland-Altman analyses revealed small mean differences with narrow limits of agreement between platforms (mean differences: 6 ±â€¯128 to 100 ±â€¯179), for inter-observer (mean differences: 1 ±â€¯43 to 12 ±â€¯70), and intra-observer variability (mean differences: 9 ±â€¯42 to 20 ±â€¯96). Observer 1 assigned 11 (kappa: 0.85-0.97) and observer 2 assigned 10 patients (kappa: 0.88-0.95) to different likelihood groups of severe aortic stenosis with at least one platform. Overall, there was no significant difference of likelihood assignment between platforms (p = 0.98 and p = 1.0, respectively). CONCLUSION: While absolute values differ slightly, common commercially available software platforms produce comparable results for AVC scoring, which indicates software-independence of the method.

Risk factors for nasal malignancies in German men: the South-German Nasal cancer study.

BACKGROUND: There are few studies of the effects of nasal snuff and environmental factors on the risk of nasal cancer. This study aimed to investigate the impact of using nasal snuff and of other risk factors on the risk of nasal cancer in German men. METHODS: A population-based case-control study was conducted in the German Federal States of Bavaria and Baden-Württemberg. Tumor registries and ear, nose and throat departments provided access to patients born in 1926 or later. RESULTS: Telephone interviews were conducted with 427 cases (mean age 62.1 years) and 2.401 population-based controls (mean age 60.8 years). Ever-use of nasal snuff was associated with an odds ratio (OR) for nasal cancer of 1.45 (95% confidence interval [CI] 0.88-2.38) in the total study population, whereas OR in smokers was 2.01 (95% CI 1.00-4.02) and in never smokers was 1.10 (95% CI 0.43-2.80). The OR in ever-smokers vs. never-smokers was 1.60 (95% CI 1.24-2.07), with an OR of 1.06 (95% CI 1.05-1.07) per pack-year smoked, and the risk was significantly decreased after quitting smoking. Exposure to hardwood dust for at least 1 year resulted in an OR of 2.33 (95% CI 1.40-3.91) in the total population, which was further increased in never-smokers (OR 4.89, 95% CI 1.92-12.49) in analyses stratified by smoking status. The OR for nasal cancer after exposure to organic solvents for at least 1 year was 1.53 (1.17-2.01). Ever-use of nasal sprays/nasal lavage for at least 1 month rendered an OR of 1.59 (1.04-2.44). The OR after use of insecticides in homes was 1.48 (95% CI 1.04-2.11). CONCLUSIONS: Smoking and exposure to hardwood dust were confirmed as risk factors for nasal carcinoma. There is evidence that exposure to organic solvents, and in-house use of insecticides could represent novel risk factors. Exposure to asbestos and use of nasal snuff were risk factors in smokers only.

Menopausal hormone therapy and risk of lung cancer-Systematic review and meta-analysis.

OBJECTIVES: Lung cancer rates increase among women in many regions of the world. To explore whether menopausal hormone therapy (MHT) plays a role. METHODS: We conducted a systematic search of the literature and performed meta-analyses of cohort studies (C), case-control studies (CC), randomized controlled trials (RCTs), and cancer registry studies (CR) to analyse the impact of estrogen therapy (ET), estrogen/progestin therapy (EPT) and any hormone therapy (HT) on lung cancer risks. We explored associations between ever-use of therapies and risks, analysed annual changes of risk, and the impact of therapies on histological subtypes. We calculated summary odds ratios, relative risks, 95% confidence intervals (CI; fixed-effects model), and assessed heterogeneity across studies. Eighteen studies were eligible (9 CC, 4 C, 3 RCT, 2 CR). RESULTS: We found a significant increase of risk - 76.2% - in non-smoking women with adenocarcinoma (CI 1.072-2.898) reporting ever-use of HT. Estrogen plus progestin therapy does not change the risk; however, the pooled analysis of 2 RCTs points at an increased risk (RR 1.359; CI 1.031-1.791). Our further results should be interpreted with caution as significances were found in analyses only when smoking and non-smoking women, various hormone regimens, or histological subtypes, respectively, were pooled. CONCLUSIONS: Dedicated studies designed to more adequately delineate the role of MHT are necessary to substantiate whether use of MHT is a risk factor for this or other types of lung cancer.

[Systematic evaluation of the proximal cardiac veins for echocardiographic diagnosis of total anomalous pulmonary venous connection]. / Nichtinvasive Diagnostik der totalen Lungenvenenfehleinmündung durch systematische echokardiografische Darstellung der herznahen Venen.

PURPOSE: Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiovascular malformation that is characterized by an absent connection of the pulmonary veins to the left atrium. Echocardiographic differentiation of TAPVC and persistent pulmonary hypertension of the newborn (PPHN) can be a great diagnostic challenge. The aim of our study was the assessment of a systematic echocardiographic approach to evaluate the feasibility and reliability of noninvasive diagnosis of TAPVC. METHODS: Between January 1995 and January 2005, 15 consecutive patients with isolated TAPVC were diagnosed in our institution. 5 patients had supracardiac type, 5 cardiac type, 3 infracardiac and 2 had mixed type of TAPVC. Since 2001 preoperative diagnosis was performed exclusively by echocardiography (8/15 patients). RESULTS: TAPVC could be diagnosed correctly in all cases using a systematic echocardiographic approach with careful investigation of the proximal cardiac veins. Infracardiac type ofTAPVC was diagnosed using systematic evaluation of the liver with visualization of a pathological vessel with venous flow directed away from the heart. In all cases the echocardiographic findings were confirmed during surgery. CONCLUSION: Echocardiography with Doppler and color Doppler sonography is an effective method for noninvasive diagnosis of TAPVC. The presented systematic echocardiographic approach permits reliable noninvasive differentiation of TAPVC and PPHN.

Menopausal hormone therapy and risk of ovarian cancer: systematic review and meta-analysis.

Knowledge about the impact of menopausal hormone therapy (MHT) on the risk of ovarian cancer (OvC) is insufficient, and studies are inconsistent. Mortality from OvC ranks highest among cancer sites in female reproductive organs. We performed meta-analyses to assess the impact of specified types of MHT on the risk of OvC in cohort studies (CS), case-control studies (CCS), randomized controlled trials (RCT) and cancer registry studies (CRS). We used data published 1966-2006 on estrogen therapy (ET), estrogen/progestin therapy (EPT) or MHT (unspecified regimen) identified by a structured, computerized and manual literature search. We identified 42 studies (30CCS, 7CS, 1 RCT and 4 CRS) with 12 238 cases. The risk of OvC (ever-use, annual risk) is increased 1.28-fold by ET [confidence interval (CI) 1.18-1.40] and 1.11-fold by EPT (CI 1.02-1.21) with a suggestion of greater risks with ET. There appears to be no differential impact of any therapy on histological subtypes. Risks were greater in European than North American studies for both ET and EPT. In conclusion, ET as well as EPT, are risk factors for OvC. Given the widespread use of MHT, known benefits should be weighed against the increased risk of OvC, and more studies are warranted, particularly on factors with the greatest apparent risks.

Menopausal hormone therapy and risk of breast cancer: a meta-analysis of epidemiological studies and randomized controlled trials.

We conducted meta-analyses to assess the impact of menopausal hormone therapy (MHT) on the risk of incident invasive breast cancer (BC) in cohort studies (CS), case-control studies (CCS) and randomized controlled trials (RCTs) published 1989-2004. We used published data providing information upon unopposed estrogen therapy (ET), estrogen-progestin therapy (EPT) or all MHT combined. Major outcomes were MHT-associated overall risk of BC and change of risk per year used. There is a linear increase of overall risk by midterm year of case ascertainment based upon data of all study types for MHT and to a larger extent for EPT, not for ET. Effects are larger in CS than in CCS. Meta-analyses stratified by <1992 versus > or =1992 as midterm year of case ascertainment indicate larger summary risks for the latter period for all MHT analysed, in particular for EPT. Annual increases in BC risk for EPT across study types are 0-9%, for ET 0-3%. In conclusion, there is evidence that relative risks for BC risks by MHT, in particular EPT, have been increasing in recent years. Given the widespread use of MHT, and often long duration, more detailed knowledge about differential BC risks of both estrogens and progestins are necessary to minimize BC risk in symptomatic women who consider MHT.

Human external ophthalmomyiasis occurring in Barbados

Human infection with the sheep nasal botfly Oestrus ovis occurs sporadically. In most cases, there is a history of a strike in the eye by the adult fly. Human O. ovis has been reported rarely from the Americas. We report the first case of O. ovis infection in the Caribbean region, which occurred in an urban area of Barbados. The patient responded to removal of the larvae from the conjunctiva and symptomatic treatment

Canine onchocercosis in Greece: report of further 20 cases and molecular characterization of the parasite and its Wolbachia endosymbiont.

Recently, sporadic cases of subconjunctival Onchocerca infection have been reported in dogs in Greece and Hungary. Herein we report further cases from Greece and the results of the molecular analysis of Onchocerca sp. removed from Greek dogs and its Wolbachia endosymbionts. Twenty dogs of various breeds, 1-11 years of age with subconjunctival onchocercosis (4 cases each in right or left eye, 12 cases in both eyes) were presented having similar manifestations. Periorbital swelling, exophthalmos, lacrimation, discharge, photophobia, conjunctival congestion, corneal edema, protrusion of the nictitating membrane, and subconjunctival granuloma or cyst formation were the most important clinical signs. After surgical excision of the periocular masses containing the worms, all animals recovered fully from onchocercosis. Based on the similarities of the clinical picture of the Greek and Hungarian cases, the similar morphology of the Greek and Hungarian isolates, and the identical sequences of the cytochrome oxidase gene of the filarial parasites and that of the 16S ribosomal RNA gene from their Wolbachia endosymbionts, the Onchocerca sp. isolated from dogs in Greece and Hungary appears to belong to the same species.

Ocular Onchocerca infections in two dogs in western United States.

Two dogs, one from California and one from Arizona, were found to have aberrant infections caused by filarial nematodes of the genus Onchocerca. In both cases, the parasites are localized in or near the eye. In one case the worm was located in the cornea and was surgically removed. In the second case, a very marked granulomatous reaction was induced in the retrobulbar space, mimicking an abscess. This eye was enucleated. The worms in both instances were female, and were gravid, i.e. contained microfilariae in utero, indicating that a male worm(s) had been present and mating had occurred. The exact identity of the species of Onchocerca responsible cannot be determined, although the features observed are most like Onchocerca lienalis of cattle. These cases represent the fourth and fifth such cases reported from the US, and are especially interesting because of the unusual location of the worms, the small number of recognized cases, and the similarity to a recent zoonotic human infection.

Evaluation of Streck tissue fixative, a nonformalin fixative for preservation of stool samples and subsequent parasitologic examination.

We undertook a study to evaluate Streck tissue fixative (STF) as a substitute for formalin and polyvinyl alcohol (PVA) in fecal preservation. A comparison of formalin, PVA, (mercuric chloride based), and STF was done by aliquoting fecal samples into each fixative. Stool specimens were collected in Haiti, and parasites included Cyclospora cayetanensis, Giardia intestinalis, Entamoeba coli, Iodamoeba butschlii, Endolimax nana, Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis, and Necator americanus. Preserved stools were examined at various predetermined times (1 week, 1 month, and 3 months) to establish the quality of the initial preservation as well as the suitability of the fixative for long-term storage. At each time point, stool samples in fixatives were examined microscopically as follows: (i) in wet mounts (with bright-field and epifluorescence microscopy), (ii) in modified acid-fast-, trichrome-, and safranin-stained smears, and (iii) with two commercial test kits. At the time points examined, morphologic features remained comparable for samples fixed with 10% formalin and STF. For comparisons of STF- and 10% formalin-fixed samples, specific findings showed that Cyclospora oocysts retained full fluorescence, modified acid-fast- and safranin-stained smears of Cryptosporidium and Cyclospora oocysts were equal in staining quality, and results were comparable in the immunofluorescence assay and enzyme immunoassay commercial kits. Stool fixed in STF and stained with trichrome showed less-than-acceptable staining quality compared with stool fixed in PVA. STF provides an excellent substitute for formalin as a fixative in routine examination of stool samples for parasites. However, modifications to the trichrome staining procedures will be necessary to improve the staining quality for protozoal cysts fixed in STF to a level comparable to that with PVA.

Subconjunctival infection with Dirofilaria repens: serological confirmation of cure following surgery.

Cases of zoonotic dirofilariasis infection, caused by Dirofilaria repens, occur widely throughout European, African, Middle Eastern, and Asian countries. The reports of this infection in humans in Spain are limited, and we herein report the case of a 43-year-old man from Elche (Alicante), Spain, who was seen with acute hyperemic reactivity of the temporal limbus of the right eye. A large nematode was visualized on examination and the intact worm was surgically removed. The parasite was identified as a mature but infertile female D repens. The level of serum antibodies against D repens was monitored for 6 months after surgery using immunoenzymatic assays. Serological results confirmed, as expected, the presence of a single worm and the parasitological cure after the surgical removal of the parasite. To our knowledge, this is the fourth autochthonous case of D repens infecting humans in Spain and also the first autochthonous case of subconjunctival localization.

Zoonotic Onchocerca (Nematoda:Filarioidea) in the cornea of a Colorado resident.

OBJECTIVE: A female patient, resident in the state of Colorado, presented with iritis of the right eye. Slit-lamp examination showed the presence of a thin, threadlike worm entwined in the cornea. The patient was taken to surgery for removal of the parasite. DESIGN: A case report. INTERVENTION: A 3-mm-long supertemporal incision was made in the cornea and further dissected until the worm could be grasped and removed by gentle traction. RESULTS: The worm, a filarial nematode, was identified as a member of the genus Onchocerca, most likely Onchocerca cervicalis, a natural parasite of horses. The patient had an uneventful recovery, and 1 week after surgery, her visual acuity, intraocular pressure, and corneal edema were all resolving. CONCLUSION: In the United States and elsewhere, most cases of zoonotic filarial infection involving the eye are caused by Dirofilaria or Dipetalonema-like worms. However, the current case was caused by a species of Onchocerca. This is the first case of zoonotic Onchocerca from the eye to be reported, only the second case of zoonotic Onchocerca in the United States, and the seventh case worldwide. The worm was removed surgically, and the patient had an uneventful recovery.

Growth effects of alpha-interferon but not of bombesin or angiotensin II are mediated by activation of STAT proteins.

BACKGROUND: The recently discovered Jak/STAT signal transduction pathway is associated with cytokine or growth factor receptors; whether members of the G protein-coupled receptor superfamily also activate this pathway is not yet clear. As a first member, the angiotensin (AT)1A receptor has been demonstrated to phosphorylate Jak and STAT proteins. Bombesin, a neurotransmitter and growth factor in many cells and tissues, activates its G protein-coupled receptor and in addition phosphorylates proteins that might be members of the Jak/STAT family. This study investigated whether bombesin- or angiotensin-mediated growth effects are associated with STAT protein activation. METHODS: Functional receptors were characterized using ligand-binding studies, second-messenger activation and determination of ligand-mediated growth effects. STAT protein activation was analysed by electrophoretic mobility shift assay (EMSA) using labelled DNA response elements recognizing all known STAT proteins. RESULTS: Functional bombesin receptors mediating mitogenic effects were demonstrated on Swiss 3T3 fibroblasts, human melanoma cells (A375-6) and primary human lung fibroblasts; however, bombesin-related STAT protein activation was not observed by EMSA. Interferon-alpha typically activated a STAT1-STAT2-p48 heterotrimer, as well as STAT1-3 hetero- and homodimers in human melanoma cells and significantly inhibited growth of this cell line in vitro. Functional AT1A receptors on primary rat cardiac fibroblasts mediated angiotensin-stimulated growth effects but, in contrast to recently published data, did not activate any known STAT protein. CONCLUSION: Interferon alpha-stimulated growth inhibition is mediated by activation of the Jak/STAT pathway, whereas bombesin or AT1A receptor-mediated effects on cellular proliferation do not involve phosphorylation of STAT proteins.