Nosocomial outbreak of monoclonal VIM carbapenemase-producing Enterobacter cloacae complex in an intensive care unit during the COVID-19 pandemic: an integrated approach.

BACKGROUND: An outbreak of VIM carbapenemase-expressing Enterobacter cloacae complex occurred between March and October 2020 in an intensive care unit (ICU) of a tertiary care and teaching hospital in France. At the same time, the hospital was facing the COVID-19 first wave. AIM: To describe the management of an outbreak caused by a VIM-producing Enterobacter cloacae complex strain during the COVID-19 pandemic in an ICU and to show the importance of an integrated approach. METHODS: A multi-focal investigation was conducted including descriptive and molecular epidemiology, environmental screening, and assessment of infection prevention and control measures. FINDINGS: A total of 14 cases were identified in this outbreak with a high attributable mortality rate (85.7%). The outbreak management was coordinated by a crisis cell, and involved the implementation of multi-disciplinary actions such as: enhanced hygiene measures, microbiological and molecular analysis of patients and environmental E. cloacae complex strains, and simulation-based teaching. All 23 E. cloacae complex strains isolated from patients and environment samples belonged to multi-locus sequence type ST78 and carried bla-VIM4 gene. Using Fourier transform infrared spectroscopy, all but two isolates were also found to belong to a single cluster. Although the source of this outbreak could not be pinpointed, the spread of the strain was controlled thanks to this multi-focal approach and multi-disciplinary implementation. CONCLUSION: This investigation highlighted the usefulness of Fourier transform infra-red spectroscopy in the rapid typing of outbreak strains as well as the importance of an integrated approach to successfully fight against multidrug-resistant micro-organism dissemination and healthcare-associated infections.

Lonomia caterpillar envenoming in French Guiana reversed by the Brazilian antivenom: A successful case of international cooperation for a rare but deadly tropical hazard.

In the American continent, larval forms (caterpillars) of the Lonomia genus can cause systemic reactions in human beings. In this Paper, we report the third case of Lonomia envenoming recorded in French Guiana in 25 years, and the first in which specific antivenom was administered. Severe symptoms of the envenoming were observed in our patient including pain; coagulopathy and systemic hemorrhage. They are caused by skin contact with caterpillars. Recovery, however, was quite satisfactory thanks to the international cooperation of the health authorities in both France and Brazil.

Role of food in the stimulation of cytokine production.

To study the role of food in the stimulation of cytokine production, the effects of lactic bacteria on production of interferon alpha, beta, and gamma; interleukin 1 beta; and tumor necrosis factor alpha were evaluated in mice and humans. Yogurt bacteria induced plasma interferon alpha and beta production in mice. Yogurt intake containing 10(11) bacteria led to increased 2'-5' A synthetase activity in human blood mononuclear cells. This result may suggest an interferon action in a peripheral way. This effect was also found when subjects consumed 10(8) yogurt bacteria/d for 15 d. In an in vitro model, blood mononuclear cells cultured in the presence of yogurt bacteria produced interleukin 1 beta, tumor necrosis factor, and interferon alpha and gamma. These results suggest the involvement of a certain type of food in cytokine production under healthy conditions.

Serum osteocalcin regulation in protein-energy malnourished children.

To evaluate bone turnover changes occurring during protein-energy malnutrition, serum osteocalcin, a marker of bone formation, has been studied in healthy control, stunted, and severely malnourished (kwashiorkor and marasmus) Senegalese children. Serum osteocalcin levels were dramatically reduced in stunted, kwashiorkor, and marasmic children compared with control children. In addition serum osteocalcin levels of control children living in Senegal were lower (-46%) than those of African children living in France. Interestingly, serum osteocalcin level was not related to its major known regulators (1 alpha,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol, and PTH) nor to stunting, but was related to serum transthyretin and thyroid hormones concentrations. These data suggest that serum osteocalcin level is related to protein-energy status and that bone formation was affected in apparently healthy and in malnourished Senegalese children. Serum osteocalcin could be a potent tool in the study of the alterations of bone formation in malnutrition.

Rat serum osteocalcin concentration is decreased by restriction of energy intake.

We studied the effects of energy restriction on serum osteocalcin concentration and bone formation rate in rats. The experiment was designed to achieve energy restriction by reducing the carbohydrate intake while providing identical quantities of protein, fat, vitamins and minerals. Energy intakes of three groups of post-weaning male rats were restricted by 20, 40 and 60% for 4 wk. Serum calcium, phosphorus, transthyretin, triiodothyronine (T3), thyroxine (T4), 1,25-dihydroxycholecalciferol, 25-hydroxycholecalciferol and immunoreactive parathyroid hormone (iPTH) concentrations were determined. Energy restriction (20, 40 and 60%) produced a significant and gradual drop of serum osteocalcin concentrations, although the serum concentrations of its key regulators, i.e., 1,25-dihydroxycholecalciferol and iPTH, were not significantly affected. On the contrary, serum concentrations of calcium, phosphorus, transthyretin, T3 and T4 were significantly lower in the energy-restricted groups. However, our results do not support their implication in the regulation of serum osteocalcin synthesis by energy intake. Serum osteocalcin concentration was positively correlated with bone mineral apposition (r = 0.50, P < 0.05) and bone mineralization (r = 0.50, P < 0.05) rates suggesting that its decrease resulted from a reduction of bone formation, and not from abnormal mineralization, because osteoid seam thickness was not modified. Energy intake seems to be an important determinant of serum osteocalcin concentration and bone formation; however, the exact mechanism underlying this regulation remains to be determined.

Plasma zinc and copper in Paris area preschool children with growth impairment.

Plasma zinc, copper, and parameters of growth were measured in a group of 116 French preschool children, 2-5 yr-old from low-income households. Participants were selected on the basis of Z-scores of weight for height (WHZ) and height for age (HAZ). Zinc and copper concentrations of children with growth impairment (GI), defined by a WHZ and/or HAZ < -1 Z-score, were compared to those of age, sex, and ethnic origin matched controls (WHZ and HAZ > -1 Z-score). Mean (+/- SD) plasma zinc concentration was 12.58 +/- 1.84 mumol/L in the GI group, and 13.27 +/- 1.98 mumol/L in the controls. The difference of the means of paired samples was 0.69 +/- 2.34, and by paired t-test the significance reached p = 0.028. This effect was primarily a result of the weight retarded group (WHZ < -1 Z-score, p < 0.009) and to the girls (p < 0.05). There were no significant differences in plasma copper concentrations between groups. These results suggest the presence of marginal zinc deficiency in French preschool children with low weight for height Z-scores.

Decreased serum levels of nutritional biochemical indices in healthy children with marginally delayed physical growth.

Biochemical markers of nutritional status (albumin, transthyretin, insulin-like growth factor-I and zinc) were measured in slowly growing two- to five-year-old, low-income Parisian children whose weight-for-height or height-for-age z scores (WHZ or HAZ) were between -1 and -2 SD of the NCHS median. The results were compared to controls who were matched for age, sex, and ethnic origin with WHZ and HAZ between -1 and +2 SD. Mean serum levels of transthyretin, albumin and insulin-like growth factor-I and mean plasma zinc concentrations were significantly lower in the growth-impaired children than in the controls (p = 0.002, p = 0.006, p = 0.015, and p = 0.035, respectively). While the height-retarded children had low mean serum insulin-like growth factor-I values, the weight-retarded subjects had decreased levels of albumin, transthyretin and zinc when compared to controls. Lower mean levels of nutritional markers in healthy, slowly growing children suggest that inadequate dietary intakes of zinc, protein and/or energy may result in marginal delays in weight and height gains.

Luteinizing hormone regulation by sex steroids in men with germinal and Leydig cell tumours.

OBJECTIVE: We examined the gonadotrophin secretion in patients with increased plasma concentrations of testosterone and oestradiol due to hCG-producing tumours. DESIGN: Comparison of plasma gonadotrophin concentrations before and after stimulation by GnRH, in eight men with hCG-producing tumours resulting in increased testosterone and oestradiol plasma levels, and in 29 men with Leydig cell tumours resulting in increased oestradiol and normal to low testosterone plasma levels. PATIENTS: Eight men with hCG-producing tumours (six with testicular tumours, two with extratesticular tumours), 29 men with Leydig cell tumours and 15 normal men. The six men with germinal cell tumours of the testis were studied before and after unilateral orchidectomy. MEASUREMENTS: Plasma concentrations of hCG, testosterone and oestradiol were measured before and after intramuscular injection of hCG. LH and FSH were measured before and after intravenous injection of 100 micrograms GnRH. RESULTS: Plasma LH and FSH concentrations were low in patients with germ cell tumours, who exhibited increased plasma testosterone and oestradiol concentrations, and were normal in patients with Leydig cell tumours, in whom oestradiol only was increased. Plasma LH and FSH were normalized in the five patients with successful (e.g. normal hCG, testosterone and oestradiol) unilateral orchidectomy. Basal plasma testosterone concentrations correlated positively (P < 0.01) with plasma oestradiol concentrations in patients with germ cell tumours and negatively (P < 0.01) in patients with Leydig cell tumours. CONCLUSIONS: In patients with hCG-secreting germ cell tumours complete suppression of plasma LH and FSH with increased plasma concentrations of both testosterone and oestradiol are often discovered. No such gonadotrophin suppression is found in patients with Leydig cell tumours, but the negative correlation observed between plasma testosterone and oestradiol in these patients suggests a weak negative feedback effect of oestradiol on LH secretion, which cannot be demonstrated by basal LH measurements in plasma.

A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population.

Forty-four institutionalized elderly subjects with body mass indexes (BMI) of either > or = 24 or < or = 21 participated in a 16-wk crossover study designed to determine the effects of low-dose zinc supplementation [306 mumol (20 mg)/d] on food intake, anthropometry, and biochemical and immunological indexes. Initial serum zinc concentrations were low in both groups and increased by approximately 20% after zinc supplementation. Zinc supplementation allowed a partial but significant restoration of serum thymulin activity and improved nutritional status (food intake and serum albumin and transthyretin concentrations) but had no effect on anthropometric indexes or serum apolipoproteins, except apolipoprotein CII and apolipoprotein CIII. After zinc supplementation, serum copper concentration decreased but there was no change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol. Low-dose zinc supplementation allows restoration, at least partially, of nutritional and thymic status without the known disadvantages of high doses of zinc.

Restoration of the thymus in aging mice by in vivo zinc supplementation.

A multiparametric study of the thymus was performed in normal aging mice (12-15 months old) submitted to a mild oral zinc supplementation during 3-6 months as compared to age-matched control mice. First, this study demonstrated that in rodents, zinc levels are significantly reduced with aging and can be restored to values close to those observed in young animals after 6 months of zinc supplementation. Second, our data showed that oral zinc administration stimulates thymus growth and partially restores the microenvironmental as well as lymphoid compartments of the organ. Regarding thymic endocrine function, a significant increase in thymulin levels and a concomitant decrease in plasma thymulin inhibitors were observed, suggesting that the age-related decline of thymic function might at least partially be due to extrinsic factors, such as zinc deficiency. The total number of thymic lymphocytes was consistently increased, without significant changes in CD4/CD8 defined thymocyte subsets. Finally, structural changes of the thymus epithelium were also detected, including the disappearance of epithelial cysts frequently observed in old animals, reappearance of a normal pattern of the thymic epithelial cell network, and a decrease in the extracellular matrix network. Taken together, these data suggest that aging-related physiological zinc deficiency induces some relevant changes in thymus structure and function which can be partially corrected by a mild oral zinc supplementation.

Selenium status of healthy immigrant Parisian preschool children.

Plasma selenium (Se) concentration and erythrocyte glutathione peroxidase activity (GPx) were assessed in a population of healthy preschool children two to five years old, residing in the city of Paris. In the 118 subjects, mean (+/- SD) plasma Se concentration was 62.10 +/- 13.96 micrograms/L, and mean GPx activity was 23.58 +/- 8.52 U/g Hb. Mean plasma Se of male children was significantly (p = 0.001) higher (12%) than levels of girls. Plasma selenium levels were not correlated with erythrocyte GPx activity. Children from Mediterranean origin had a slightly lower erythrocyte GPx activity (p < 0.05) than children from other regions. Mean plasma Se concentration of this group corresponded to the lower limit of intervals, which characterizes geographical regions of intermediate selenium concentrations.

Rat serum osteocalcin concentration is determined by food intake and not by inflammation.

Osteocalcin, or bone gla protein, is the major noncollagenous protein in bone. Previous findings of decreased serum osteocalcin concentrations in children with Kwashiorkor led us to analyze the respective influence of nutritional status and inflammation on circulating osteocalcin in growing rats. Food deprivation for 72 h induced a significant 24% decrease in serum osteocalcin. Refeeding produced a rapid rise in serum osteocalcin, which reached control concentrations after 24 h of refeeding. Bone osteocalcin was not affected by these dietary manipulations. The changes in serum osteocalcin were not correlated with serum 1,25-dihydroxycholecalciferol, whereas they could be related to serum 25-hydroxycholecalciferol concentrations. Turpentine injection reduced serum osteocalcin concentration, but pair-feeding showed that this decrease was entirely attributable to spontaneous food restriction and not to inflammation. By contrast, the sensitive nutritional marker, serum transthyretin, was affected by both inflammation and food restriction. These results indicate that serum osteocalcin is closely related to food intake but not to inflammation, suggesting that the dramatic decrease in serum osteocalcin that we previously observed in children with Kwashiorkor is due to malnutrition per se.

Zinc supplements in breastfed infants.

Among breastfed infants, growth faltering in comparison with reference growth curves is common in both developing and developed countries. We performed a zinc supplementation trial in Paris, France, to find out whether such growth faltering is due to nutritional zinc deficiency. 57 breastfed infants aged 4-9 (mean 5.7) months were randomly assigned to receive either 5 mg zinc daily or a placebo for 3 months. Most of the infants were from low-income immigrant families and the majority were of African origin. Before supplementation there were no significant differences between the zinc and placebo groups in weight, length, or corresponding Z-scores for age. After 3 months' supplementation, the length-for-age Z-score had increased in the zinc group and fallen in the placebo group (+0.21 vs -0.13, p = 0.029). This difference was due mainly to greater linear growth of boys in the zinc than in the placebo group (6.0 vs 4.6 cm, p = 0.02). Weight gain was also significantly greater with zinc supplementation (1.64 vs 1.28 kg, p = 0.047). Among infants breastfed for longer than 4 months, decreases in growth velocity result partly from inadequate zinc intake.

Interferon induction by Lactobacillus bulgaricus and Streptococcus thermophilus in mice.

This study investigates the effect of intraperitoneal injection of L. bulgaricus and S. thermophilus on interferon production by Swiss mice. The serum from mice given 5 x 10(7) L. bulgaricus in 0.5 ml saline showed a maximal production of 300 U/ml of alpha/beta interferon activity six hours after injection. Cellular integrity appears to be necessary for stimulation; heat-treated bacteria had little effect, while irradiated-bacteria had a greater effect. TNF was also produced, the sera of mice with high IFN also contained 300 U/ml TNF. Streptococcus thermophilus produced no detectable increase in serum IFN, but the 2'-5' A synthetase activity of peritoneal cells was elevated suggesting that small amounts of interferon were produced. Injection of Streptococcus thermophilus plus Lactobacillus bulgaricus did not change the serum interferon response to L. bulgaricus. These observations suggest that non-pathogenic bacteria such as those used in food processing, can stimulate IFN production in mice. There is some evidence that the bacterial cell walls might be responsible for at least part of this effect.

Discrepancy between anthropometry and biochemistry in the assessment of the nutritional status of the elderly.

Institutionalized aged subjects, considered free of evolutive disease and whose body weight was stable, were studied. They were divided into two groups depending on their body mass index: controls (BMI greater than or equal to 24) and depleted (BMI less than or equal to 21). The depleted group, as judged by anthropometric measurements, showed dramatically reduced body muscle and adipose masses. Usual blood parameters were normal in both groups. Biochemical markers of the protein and energy status, viz. albumin, transthyretin, transferrin, somatomedin-C, as well as serum levels of osteocalcin and apolipoproteins AI, AII, B, CII, CIII and E, were not affected in the depleted group. However, moderate iron deficiency and marked zinc deficiency were found in this group. It is concluded that in the elderly, biochemical markers of the protein and energy status are not related to the nutritional status assessed by anthropometry.

Induction of 2'-5' A synthetase activity and interferon in humans by bacteria used in dairy products.

The production of interferon by fasted human subjects in response to lactic bacteria Lactobacillus bulgaricus and Streptococcus thermophilus was evaluated in vivo and in vitro. The 2'-5' A synthetase activity of blood mononuclear cells was used to estimate interferon production following a single ingestion of 10(11) bacteria in yoghurt or sterile milk (controls). The level of the 2'-5' A synthetase of the yoghurt fed subjects was 83% (p = 0.002) higher than that of the milk fed controls 24 hours after ingestion. The baseline value remained unchanged in the control group. Blood mononuclear cells from a second group of subjects, were cultured with lactic bacteria for 48 hours, their cell-free supernatants contained gamma interferon. These results suggest that a transient production of interferon can be induced in healthy subjects by the lactic bacteria used in food processing.

[Nutritional regulation of serum osteocalcin: study in kwashiorkor]. / Régulation nutritionnelle de l'ostéocalcine sérique: étude dans le kwashiorkor.

The serum levels of osteocalcin (bone gla protein) in two groups of Senegalese children, healthy controls and severely malnourished (kwashiorkor) children during nutritional rehabilitation, were measured. The serum osteocalcin of all kwashiorkor children was dramatically decreased on admission to hospital, but increased fourfold during rehabilitation. Serum osteocalcin was low in the control group. In both groups these low levels seemed to be independent of those of 1,25-dihydroxyvitamine D3 which were in the normal range. The results suggest that serum osteocalcin levels might be related to protein-energy status.

[Endoscopic urethrotomy. Resection, anastomosis and cutaneous urethroplasty. Results of the Normandy Society of Urology]. / Urétrotomie endoscopique. Résections anastomoses et urétroplasties cutanées. Résultats de l'Association des Urologues de Normandie.

Although urethrotomy alone gives poor results at 5 years, these results are greatly improved by repeated urethrotomy. This treatment is particularly useful in patients at risk, especially as it can be easily performed under local anaesthesia. The authors confirm the reliability of resection-anastomoses, the superiority of one-stage urethroplasty over two-stage urethroplasty and the poor prognosis associated with a history of repeated dilatations and infectious aetiology.