Characteristics of human metapneumovirus infection in adults hospitalized for community-acquired influenza-like illness in France, 2012-2018: a retrospective observational study.

OBJECTIVES: To describe the prevalence, clinical features and complications of human metapneumovirus (hMPV) infections in a population of adults hospitalized with influenza-like illness (ILI). METHODS: This was a retrospective, observational, multicenter cohort study using prospectively collected data from adult patients hospitalized during influenza virus circulation, for at least 24 h, for community-acquired ILI (with symptom onset <7 days). Data were collected from five French teaching hospitals over six consecutive winters (2012-2018). Respiratory viruses were identified by multiplex reverse transcription polymerase chain reaction (RT-PCR) on nasopharyngeal specimens. hMPV + patients were compared with hMPV- patients, influenza+ and respiratory syncytial virus (RSV)+ patients using multivariate logistic regressions. Primary outcome was the prevalence of hMPV in patients hospitalized for ILI. RESULTS: Among the 3148 patients included (1449 (46%) women, 1988 (63%) aged 65 and over; 2508 (80%) with chronic disease), at least one respiratory virus was detected in 1604 (51%, 95% confidence interval (CI) 49-53), including 100 cases of hMPV (100/3148, 3% 95% CI 3-4), of which 10 (10%) were viral co-infection. In the hMPV + patients, mean length of stay was 7 days, 62% (56/90) developed a complication, 21% (14/68) were admitted to intensive care unit and 4% (4/90) died during hospitalization. In comparison with influenza + patients, hMPV + patients were more frequently >65 years old (adjusted odds ratio (aOR) = 3.3, 95% CI 1.9-6.3) and presented more acute heart failure during hospitalization (aOR = 1.8, 95% CI 1.0-2.9). Compared with RSV + patients, hMPV + patients had less cancer (aOR = 0.4, 95% CI 0.2-0.9) and were less likely to smoke (aOR = 0.5, 95% CI 0.2-0.9) but had similar outcomes, especially high rates of respiratory and cardiovascular complications. CONCLUSIONS: Adult hMPV infections mainly affect the elderly and patients with chronic conditions and are responsible for frequent cardiac and pulmonary complications similar to those of RSV infections. At-risk populations would benefit from the development of antivirals and vaccines targeting hMPV.

Assessment of liver iron overload by 3 T MRI.

PURPOSE: To evaluate the performance and limitations of the signal intensity ratio method for quantifying liver iron overload at 3 T. METHODS: Institutional review board approval and written informed consent from all participants were obtained. One hundred and five patients were included prospectively. All patients underwent a liver biopsy with biochemical assessment of hepatic iron concentration and a 3 T MRI scan with 5 breath-hold single-echo gradient-echo sequences. Linear correlation between liver-to-muscle signal intensity ratio and liver iron concentration was calculated. The algorithm for calculating magnetic resonance hepatic iron concentration was adapted from the method described by Gandon et al. with echo times divided by 2. Sensitivity and specificity were calculated. RESULTS: Five patients were excluded (coil selection failure or missing sequence) and 100 patients were analyzed, 64 men and 36 women, 52 ± 13.3 years old, with a biochemical hepatic iron concentration range of 0-630 µmol/g. Linear correlation between biochemical hepatic iron concentration and MR-hepatic iron concentration was excellent with a correlation coefficient = 0.96, p < 0.0001. Sensitivity and specificity were, respectively, 83% (0.70-0.92) and 96% (0.85-0.99), with a pathological threshold of 36 µmol/g. CONCLUSION: Signal intensity ratio method for quantifying liver iron overload can be used at 3 T with echo times divided by 2.

Effects of phlebotomy therapy on cytochrome P450 2e1 activity and oxidative stress markers in dysmetabolic iron overload syndrome: a randomized trial.

AIM: To assess the effects of iron removal on cytochrome P450 2E1 activity and oxidative stress in dysmetabolic iron overload syndrome. METHODS: Forty-eight patients were randomized to phlebotomy therapy consisting of removal of 300-500 mL of blood every 14 days until serum ferritin levels dropped under 100 microg/L or to follow-up without phlebotomy therapy. Cytochrome P450 2E1 activity was measured at baseline and at the end of treatment by using the 6-hydroxychlorzoxazone/chlorzoxazone blood metabolic ratio, 2 h after the intake of 500 mg of chlorzoxazone. RESULTS: In the treatment group, a mean of 3.9 +/- 1.3 L of blood was removed and serum ferritin levels dropped from 715 +/- 397 to 74 +/- 34 microg/L. Variation of cytochrome P450 2E1 activity was not significantly different between the 2 groups (0.07 +/- 0.26 vs. 0.03 +/- 0.19, P = 0.36). In the treatment group, low-density lipoprotein cholesterol and vitamin E were lowered after treatment compared with control group (-0.15 +/- 0.51 vs. 0.24 +/- 0.58, P = 0.002 and -1.3 +/- 4.4 vs. 2.3 +/- 5.2, P = 0.03, respectively). Inversely, vitamin C was increased (0.5 +/- 3.5 vs. -1.8 +/- 3.9, P = 0.03). CONCLUSIONS: In dysmetabolic iron overload syndrome, reduction of iron stores does not significantly influence cytochrome P450 2E1 activity but is associated with a significant decrease of low-density lipoprotein cholesterol, suggesting that venesection therapy may be a suitable option in these patients.

Venesection therapy of insulin resistance-associated hepatic iron overload.

BACKGROUND/AIMS: The association of hepatic iron overload with metabolic disorders has been coined as the insulin resistance-associated hepatic iron overload syndrome (IR-HIO). METHODS: Fifty-six IR-HIO patients were phlebotomized either weekly (n = 14) or bimonthly (n = 42) and compared with C282Y homozygotes and with ten IR-HIO patients treated by a low calorie diet alone. RESULTS: In venesected patients, the median amount of mobilized iron was 0.6 g in 2.8 months in females and 1.8 g in 5 months in males. Mobilized iron did not differ depending on the frequency of venesections or HFE genotype. When compared with C282Y homozygotes, IR-HIO patients had a similar amount of mobilized iron, but three-fold serum ferritin levels. The presenting symptoms (chronic fatigue and/or polyarthralgias) improved in 6/7 patients. Phlebotomies were well tolerated. In patients treated by a low calorie diet, serum ferritin levels remained stable. CONCLUSIONS: In IR-HIO patients, body iron stores are significantly increased, overestimated by serum ferritin, not modified by a low calorie diet, and safely removed by phlebotomies. Based on these data and on studies indicating that iron excess is associated with increased risk for hepatic fibrosis, cancer and cardiovascular disorders, venesection therapy can be recommended in IR-HIO patients.

Clinical aspects of hemochromatosis.

Hemochromatosis is one of the most frequent genetic diseases among the white populations, affecting one in three hundred persons. Its diagnosis has been radically transformed by the discovery of the HFE gene. In a given individual, the diagnosis can, from now on, be ascertained on the sole association of a plasma transferrin saturation (TS) over 45% and homozygosity for the C282Y mutation. Liver biopsy is only required to search for cirrhosis whenever there is hepatomegaly and/or serum ferritin >1000 ng/ml and/or elevated serum AST. Family screening is mandatory, primarily centered on the siblings. The treatment remains based on venesection therapy which improves many features of the disease (one of the most refractory, however, being the joint signs) and permits normal life expectancy provided the diagnosis is established prior to the development of cirrhosis or of insulin-dependent diabetes. In view of the prevalence, the non-invasive diagnosis, the spontaneous severity and the efficacy of a very simple therapy, hemochromatosis should benefit from population screening. This screening could be based, first, on the assessment of transferrin saturation, followed - when elevated - by the search for the C282Y mutation. The discovery of the HFE gene has also paved the road for the individualization of other types of iron overload syndromes which are not HFE-related.

[Evaluation of recombinant retrovirus and adenovirus for gene transfer to normal and pathologic intestinal tissue]. / Evaluation des rétrovirus et des adénovirus recombinants pour le transfert de gènes au sein du tissu intestinal normal et pathologique.

Intestinal tract is an attractive target for gene therapy. A number of diseases could benefit from gene transfer into this organ and in particular inflammatory diseases such as Crohn's disease. In the present report, we have evaluated the efficiency of retroviral and adenoviral recombinant vectors for transferring a marker gene (beta galactosidase from E. Coli) in two parts of the intestinal tract: the small bowel and the left part of the colon. Retroviruses were inefficient for the transfer of the marker gene in these two sites either in normal conditions or after induction of inflammation by treatment with acetic acid or trinitrobenzene. Conversely, beta galactosidase positive cells were found in small bowel as well as colon following gene transfer with adenoviral vectors. Moreover the location of the positive cells in the intestinal wall was dependent upon the route of injection of the adenoviral vectors (transparietal, endoluminal or intramural).

Pulsatile tinnitus associated with congenital central nervous system malformations.

Pulsatile tinnitus as a manifestation of congenital central nervous system malformations has not been previously described. We present two patients with type I Arnold-Chiari malformation and one patient with congenital stenosis of the sylvian aqueduct with pulsatile tinnitus. Pulsatile tinnitus in these patients is believed to be secondary to increased intracranial pressure. Tinnitus subsided in one patient with Arnold-Chiari malformation after suboccipital decompression. The other two patients declined surgery. Audiologic and radiologic findings are presented, and our diagnostic algorithm for pulsatile tinnitus is described. The pathophysiology of pulsatile tinnitus can be a manifesting symptom in some patients with congenital central nervous system malformations.

Oral cavity: anatomy and pathology.

The oral cavity and oropharynx comprise the upper portion of the aerodigestive tract. These two regions are distinguished from each other because pathologic processes differ in their presentations, prognoses, and histologic grades. The normal anatomy of the oral cavity, vestibule, and oral cavity proper is discussed and is followed by a discussion of the sublingual and submandibular spaces. The diversity of pathologic processes that occur in these regions is then presented as well as the more common pitfalls.

Brain imaging in AIDS.

Although central nervous system (CNS) involvement is common in the population with acquired immunodeficiency syndrome, the presenting neurologic signs and symptoms are often vague and nonfocal. This represents a significant diagnostic challenge for the primary care physician. Cross-sectional imaging now plays an important role in the diagnosis of pathologic processes involving the brain in HIV-infected patients. Involvement of the brain with atypical viruses, parasites, fungi, and neoplasms is more prevalent in AIDS patients. On identification of a brain lesion, it is the role of the imager to characterize it in an attempt to provide a limited differential diagnosis. We review the imaging findings of the pathogens that most commonly affect the brain in AIDS patients.

Bilateral orbital granulocytic sarcoma (chloroma) preceding the blast phase of acute myelogenous leukemia: CT findings.

Granulocytic sarcoma (chloroma) is an uncommon malignant neoplasm associated with myelogenous leukemias. Its appearance may precede the clinical manifestations of the acute leukemic phase by months to years. We report the CT findings of a case of bilateral intraorbital granulocytic sarcoma which preceded the blast phase of acute myelogenous leukemia (AML) and led to its diagnosis. An awareness of granulocytic sarcoma and its CT appearance may expedite the diagnosis of AML or prompt close monitoring of those cases of granulocytic sarcoma antedating the appearance of AML.

Imaging the sphenoid bone and basiocciput: pathological considerations.

Many diverse pathologic processes can involve the sphenoid bone because of its complex embryologic origin. In addition to primary neoplasia, the central location of the sphenoid predisposes it to involvement by many intracranial and extracranial lesions. The presence of multiple foramina and fissures offer "paths of least resistance" that allow the spread of pathology across the skull base. Sphenoid sinus disease also accounts for a number of pathologic entities occurring in this vicinity. This article reviews the more common lesions affecting the sphenoid bone as well as their CT and MR appearance.

The ostiomeatal unit and endoscopic surgery: anatomy, variations, and imaging findings in inflammatory diseases.

Recent and ongoing advances made in endoscopic surgical techniques require the radiologist to understand the anatomy and pathophysiology of the paranasal sinuses and nasal passage. Endoscopy and CT are complementary procedures, and, as such, the normal anatomic relationships and their CT appearances need to be well understood in order for radiologists to offer continued support as consultants to their clinical colleagues. In this article, we review the pertinent anatomy of the lateral nasal wall and paranasal sinuses, discuss the most frequently encountered normal variations that may predispose a patient to inflammatory sinus disease, outline imaging protocols for evaluation of this region, and introduce the reader to current endoscopic surgical techniques. Last, the imaging findings in various inflammatory processes involving the sinuses, as well as the local and regional complications associated with paranasal sinus inflammatory diseases, are presented.

Tumoral thrombosis of cerebral venous sinuses: preoperative diagnosis using magnetic resonance phase imaging.

Intracranial, dural-based neoplasms will not infrequently invade adjacent venous sinuses. Therefore, the preoperative diagnosis of venous invasion is important, as it will alter the surgical approach to the lesion. Magnetic resonance imaging is a noninvasive means of visualizing the cerebral venous sinuses. The preoperative diagnosis of venous thrombosis can, however, be difficult and confusing with conventional spin-echo magnetic resonance imaging because of variable appearances produced by blood clot degradation products as well as flowing blood. Phase magnetic resonance imaging is a simple method that can be acquired simultaneously with conventional spin-echo sequences, and is based primarily on whether protons are stationary or moving. In the context of venous sinus occlusion, phase imaging can demonstrate the presence or absence of blood flow more easily than spin-echo imaging. Three cases of dural-based neoplasms are presented that demonstrate the utility of phase imaging in diagnosing tumoral occlusion of the venous sinuses.

Intracranial vascular abnormalities: value of MR phase imaging to distinguish thrombus from flowing blood.

The interpretation of conventional spin-echo and gradient-echo MR images of intracranial vascular lesions can be complex and ambiguous owing to variable effects on image intensity caused by flowing blood or thrombus. MR phase images, obtained simultaneously with conventional-magnitude images, are useful for evaluating proton motion (i.e., blood flow), and therefore can simplify the diagnosis of the presence or absence of thrombosis within a vascular structure or lesion. Fourteen patients with a variety of intracranial vascular abnormalities (aneurysms, superior sagittal sinus thrombosis, neoplasms adjacent to venous sinuses, and vascular malformations) were evaluated with conventional MR and phase imaging for the presence of blood flow. The phase images correlated with angiography in all cases. Phase imaging was not necessarily better than conventional spin-echo imaging in all cases, but it simplified the evaluation of thrombus vs blood flow in many. In three of five aneurysms, the phase images were diagnostic for evaluating lumen patency whereas the conventional images were ambiguous. Phase imaging was advantageous for detecting tumor invasion of the venous sinus when venous blood was enhanced by gadopentetate dimeglumine. A laminar flow phantom experiment determined the lower limits of sensitivity of phase imaging to be 0.5 cm/sec in the slice-select and 2.5 cm/sec in the read gradient directions. Phase imaging is a simple, reliable technique that can distinguish thrombosis from flowing blood within intracranial lesions. It is easily performed and adds no additional time to the MR examination.

Brain lesions in chronic granulomatous disease.

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.

CT and MR imaging of the central skull base. Part 2. Pathologic spectrum.

The radiologist must have a thorough knowledge of the normal anatomy and the pathologic spectrum of the skull base to determine the extent of abnormality and to help plan the surgical approach. The authors describe and present examples of congenital, benign, and malignant lesions that affect this region, including cephalocele, fracture, fistula, juvenile angiofibroma, meningioma, chordoma, pituitary adenoma, chondrosarcoma, nasopharyngeal carcinoma, and rhabdomyosarcoma. Metastatic, infectious, and other miscellaneous processes are also discussed. Imaging strategies with computed tomography and magnetic resonance imaging to aid in the diagnosis are suggested.

Intrasellar primitive neuroectodermal tumor (PNET) in familial retinoblastoma: a variant of "trilateral retinoblastoma".

An infant with bilateral familial retinoblastomas was found at age 6 months to have a large mass within the region of the sella turcica. The histology, immunoreactivity and ultrastructure of the tumor showed primitive neuroectodermal cells. A small number of cells showed positive immunostaining to retinal S antigen. This represents a rare form of so-called trilateral retinoblastoma. In most cases of trilateral retinoblastoma, the intracranial non-metastatic tumor is within the pineal gland. The occurrence of such a tumor in the region of sella turcica is very unusual and its possible significance is discussed in regard to our current understanding of the susceptibility to carcinogenesis conferred by inheritance of the mutant retinoblastoma gene, Rb-1.