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 transcutaneous tibial nerve stimulation on anorectal physiology in fecal incontinence: a double-blind placebo-controlled cross-over evaluation.

BACKGROUND: Transcutaneous electrical tibial nerve stimulation (TENS) is of growing interest for the treatment of fecal incontinence (FI), but its mechanism of action remains uninvestigated. We aimed to further assess the anorectal response to TENS in a dynamic model. METHODS: We performed a placebo-controlled, randomized, double-blinded crossover study in 19 patients suffering from FI to assess the effects of TENS on anorectal function. Anorectal physiology and perception were recorded through two sequences of rectal isobaric distension using an electronic barostat device to measure anal and rectal pressures, rectal volumes, and perception scores. KEY RESULTS: Maximal rectal pressure and volume variation were affected by TENS, with higher mean maximal rectal pressure (5.33 and 4.06 mmHg in the active and sham TENS respectively, p < 0.0001) and lower volume variation (11.45 and 14.7 mL in the active and sham stimulation respectively, p < 0.05). Rectal compliance was not modified by active TENS. Pressure of the upper anal canal was significantly lower with raised isobaric distension in sequences assigned to active TENS. CONCLUSIONS & INFERENCES: Acute TENS modified anorectal physiology by strengthening the myogenic response to distension rather than increasing muscle relaxation and related rectal compliance in patients with FI.

Biological and hemodynamic effects of low doses of fludrocortisone and hydrocortisone, alone or in combination, in healthy volunteers with hypoaldosteronism.

Low doses of hydrocortisone (HC) and fludrocortisone (FC) administered together improve the prognosis after septic shock; however, there continues to be disagreement about the utility of FC for this indication. The biological and hemodynamic effects of HC (50 mg intravenously) and FC (50 microg orally) were assessed in 12 healthy male volunteers with saline-induced hypoaldosteronism in a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 x 2 factorial design. HC and FC significantly decreased urinary sodium and potassium levels (from -58% at 4 h to -28% at 10 h and from -35% at 8 h to -24% at 12 h, respectively) with additive effects. At 4 h after administration, HC significantly increased cardiac output (+14%), decreased systemic vascular resistances (-14%), and slightly increased heart rate (+4 beats/min), whereas FC had no hemodynamic effect. At doses used in septic shock, HC induced greater mineralocorticoid effect than FC did. HC also induced transient systemic hemodynamic effects, whereas FC did not. New studies are required to better define the optimal dose of FC in septic shock.

Elastomer implants in faecal incontinence: a blind, randomized placebo-controlled study.

AIM: To test efficacy and safety of polydimethylsiloxane elastomer implants, a silicone biomaterial, in patients with severe faecal incontinence related to an impaired internal anal sphincter. METHODS: Subjects were randomized to receive three injections of 2.5 mL of either physiological saline or polydimethylsiloxane elastomer. After local anaesthesia, an 18 gauge, 2.5-in needle was inserted through the perianal skin and laid down into the intersphincteric space. Treatment (saline or polydimethylsiloxane elastomer) was administered by means of a ratchet gun. Three injections of 2.5 mL each were performed in the area of the internal anal sphincter at 3, 7 and 11 o'clock positions. Main end point was the percentage of subjects in each treatment arm experiencing a successful treatment, defined as a Cleveland Clinic Florida-Faecal Incontinence score <8, 3 months after treatment. Secondary end points were quality of life scores, weekly number of faecal incontinence episodes, subject acceptance and adverse events rate. Both patients and end point assessments were blinded to treatment. RESULTS: 44 women (64.3 +/- 9 years) with a baseline Cleveland Clinic Florida-Faecal Incontinence score > or =8 were enrolled prospectively; 22 received polydimethylsiloxane elastomer and 22 saline treatment. Treatment was well tolerated. At 3 months, the percentage of subjects experiencing a successful treatment was not different between polydimethylsiloxane elastomer and saline groups (23% vs. 27%, respectively, P = 0.73). Moreover, Cleveland Clinic Florida-Faecal Incontinence score was not significantly different between polydimethylsiloxane elastomer and saline groups (11.7 +/- 4.7 vs. 11.4 +/- 4.5, respectively, P = 0.79). CONCLUSIONS: Polydimethylsiloxane elastomer implants cannot be recommended for treatment of severe faecal incontinence related to impaired internal anal sphincter.

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.

Assessment of actinide mass embedded in large concrete waste packages by photon interrogation and photofission.

This paper describes a method based on photofission developed in our laboratory to characterize in depth large waste packages. The method consists in using photons of high-energy (Bremsstrahlung radiation) in order to induce reactions of photofission on the heavy nuclei present in the wastes. The measurement of the delayed neutrons allows quantifying the actinides in the wastes. We present the first results of measurement performed with a concrete mock-up of 870l and two real waste packages.

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.

Contribution of edema and cerebral blood volume to traumatic brain swelling in head-injured patients.

OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The generally held view is that brain swelling is caused primarily by vascular engorgement and that edema plays a relatively minor role in the swelling process. The goal of this study was to examine the roles of cerebral blood volume (CBV) and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV were measured in 76 head-injured patients, and the relative contribution of edema and blood to total brain swelling was determined. Comparable measures of brain-tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers. Brain edema was measured using magnetic resonance imaging, implementing a new technique for accurate measurement of total tissue water. Measurements of CBV in a subgroup of 31 head-injured patients were based on consecutive measures of cerebral blood flow (CBF) obtained using stable xenon and calculation of mean transit time by dynamic computerized tomography scanning after a rapid bolus injection of iodinated contrast material. The mean (+/- standard deviation) percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema is the major fluid component contributing to traumatic brain swelling. Moreover, CBV is reduced in proportion to CBF reduction following severe brain injury.

[Genetics and physiopathology of hemochromatosis]. / Génétique et physiopathologie de l'hémochromatose.

Thanks to the discovery of the HFE gene and of its mutations, it is now established that the most frequent form of hemochromatosis is related to homozygosity for the mutation C282Y, and that other types of hemochromatosis, unrelated to HFE mutations, do exist such as the juvenile hemochromatosis. From a pathophysiological standpoint, the C282Y mutation impairs HFE protein expression at the surface of the membrane and disturbs the cellular entry of iron (carried by circulating transferrin) into the cryptic duodenal cell. This, in turn, is likely to lead to an aberrant programmation of the degree of iron influx from the digestive lumen into the apical duodenal cells. The resulting hyperabsorption, which forms the basis of iron overload in hemochromatosis, is likely to implicate an overexpression of the transmembrane iron carrier DMT1. It is remarkable to observe that these major improvements in the knowledge of hemochomatosis have been accompanied by similar improvements in the understanding of normal iron metabolism.

[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).

Focal atrophy of the multifidus muscle in lumbosacral radiculopathy.

A patient with compelling clinical and electrodiagnostic evidence of a right L5 radiculopathy had focal atrophy of the multifidus at the appropriate level, which served to confirm the radicular nature of the process. The multifidus muscles are innervated by a single root, in contrast to the polysegmental innervation of the rest of the paraspinal muscle mass. Imaging studies may complement needle electromyography in the evaluation of this important structure.

Anatomy of the cranial nerves.

The anatomy of cranial nerves I and III through XII are presented. Each nerve is diagrammatically illustrated from its nuclear or its sensory origin and correlated with magnetic resonance and computed tomography images. The important identifying anatomical landmarks are demonstrated along the course of each nerve. Peripheral motor and sensory components are also discussed.

Cranial nerves III, IV, and VI.

Movements of the eye are produced by six extraocular muscles innervated by three cranial nerves: the oculomotor (III), the trochlear (IV), and the abducens (VI). These cranial nerves are discussed together because of the interrelated nuclear origins, neural pathways, and motor functions. The normal anatomic pathway of these three nerves is presented. The clinical and pathologic manifestations of lesions producing both isolated and complex palsies of these nerves are discussed along with imaging correlation.

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.