[Impact of confinement on the follow-up of oral immunotherapies: A multicentre study in the Île-de-France region]. / Impact du confinement sur le suivi des immunothérapies orales alimentaires : étude multicentrique dans 3 centres d'Île-de-France.

PURPOSE OF THE STUDY: Several studies have confirmed the impact of confinement on the population, resulting in disruption of care, somatic and psychological effects. Our study looks at adverse effects and problems of adherence to oral immunotherapy therapy (OIT) during this period. PATIENTS AND METHODS: A total of 132 patients, mostly children (95%), with an atopic history (60%) followed for an OIT were included in 3 allergology centers in Île-de-France, during the period of confinement from 03/16 to 05/11/20. The main food allergens used for OIT were peanut (38%), cow's milk (24%), hazelnut (14%), egg (9%), cashew nut and pistachio nut (8%). RESULTS: Adverse effects were found in 13 patients or 10% of the cases. These reactions were mainly grade 1 and 2 according to the Ring and Messmer classification. Three patients had grade 3 reactions and six patients used epinephrine at home. Adherence was correct in 81% of cases with no omissions. Three patients increased their daily dose without medical advice. No significant difference was found in the subgroup analysis comparing age-matched children followed up in OIT in 2019 and 2020 over the same period in the same hospital. CONCLUSION: There was no increase in adverse events in OIT during the confinement period. Therapeutic education during OIT is paramount and helps to reduce the occurrence of adverse events.

Use of tigecycline for the management of Clostridium difficile colitis in oncology patients and case series of breakthrough infections.

BACKGROUND: Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies. AIM: To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre. METHODS: This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre. FINDINGS: The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%. CONCLUSION: Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI.

Variation in human genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese.

The genetic basis for susceptibility to malaria has been studied widely in African populations but less is known of the contribution of specific genetic variants in Asian populations. We genotyped 67 single-nucleotide polymorphisms (SNPs) in 1030 severe malaria cases and 2840 controls from Vietnam. After data quality control, genotyping data of 956 cases and 2350 controls were analysed for 65 SNPs (3 gender confirmation, 62 positioned in/near 42 malarial candidate genes). A total of 14 SNPs were monomorphic and 2 (rs8078340 and rs33950507) were not in Hardy-Weinberg equilibrium in controls (P<0.01). In all, 7/46 SNPs in 6 genes (ICAM1, IL1A, IL17RC, IL13, LTA and TNF) were associated with severe malaria, with 3/7 SNPs in the TNF/LTA region. Genotype-phenotype correlations between SNPs and clinical parameters revealed that genotypes of rs708567 (IL17RC) correlate with parasitemia (P=0.028, r(2)=0.0086), with GG homozygotes having the lowest parasite burden. Additionally, rs708567 GG homozygotes had a decreased risk of severe malaria (P=0.007, OR=0.78 (95% CI; 0.65-0.93)) and death (P=0.028, OR=0.58 (95% CI; 0.37-0.93)) than those with AA and AG genotypes. In summary, variants in six genes encoding adhesion and proinflammatory molecules are associated with severe malaria in the Vietnamese. Further replicative studies in independent populations will be necessary to confirm these findings.

Insights to the clarification of sugar cane juice expressed from sugar cane stalk and trash.

Processing of juice expressed from green sugar cane containing all the trash (i.e., tops and leaves, the nonstalk component) of the sugar cane plant during sugar manufacture has been reported to lead to poor clarified juice (CJ) quality. Studies of different liming techniques have been conducted to identify which liming technique gives the best clarification performance from juice expressed from green cane containing half of all trash extracted (GE). Results have shown that lime saccharate addition to juice at 76 °C either continuous or batchwise gives satisfactory settling rates of calcium phosphate flocs (50-70 cm/min) and CJ with low turbidity and minimal amounts of mineral constituents. Surprisingly, the addition of phosphoric acid (≤ 300 mg/kg as P2O5), prior to liming to reduce juice turbidity (≤ 80%), increased the Mg (≤ 101%) and Si (≤ 148%) contents particularly for clarified GE juices. The increase was not proportional with increasing phosphoric acid dose. The nature of the flocs formed, including the zeta potential of the particles by the different liming techniques, has been used to account for the differences in clarification performance. Differences between the qualities of the CJ obtained with GE juice and that of burnt cane juices with all trash extracted (BE) have been discussed to provide further insights into GE processing.

Freeze fracture study of airway epithelium from patients with primary ciliary dyskinesia.

BACKGROUND: The airway cilia of patients with primary ciliary dyskinesia (PCD) exhibit several anomalies when studied by transmission electron microscopy, but little is known about the ultrastructural organisation of ciliary membranes in these patients. Freeze fracture replication of airway epithelium from patients with PCD provides a means of achieving high resolution views of cell membrane structure. Ciliary necklaces are a specialised structural feature of ciliary membranes thought to serve as a timing mechanism for ciliary beat, and their characterisation in the cilia of patients with PCD may contribute new insights into the pathophysiology of this syndrome. METHODS: The nasal epithelium of three patients with PCD was freeze fractured and replicated with platinum and carbon shadowing. The resultant preparations were examined by transmission electron microscopy and the ciliary necklaces were compared with similar preparations of nasal biopsy specimens from normal healthy subjects. RESULTS: The ciliary necklaces of the three patients with PCD were normal with no overt differences from those of healthy individuals. CONCLUSIONS: The defective ciliary motility observed in patients with PCD does not appear to result from membrane dysfunction associated with overt disorganisation of ciliary necklace structure.

Quantitative study of calcium uptake by tumorigenic bone (TE-85) and neuroblastoma x glioma (NG108-15) cells exposed to extremely-low-frequency (ELF) electric fields.

To verify the effect of cell culture state on frequency dependent increase in proliferation as well as Ca2+ flux across the plasma membrane, tumorigenic bone (TE-85) and neuroblastoma x glioma (NG108-15) cells cultured in the presence of fetal bovine serum (FBS) were exposed to capacitively coupled electric (CCEF) fields in the extremely low frequency (ELF) range of 10 to 18 Hz. [3H]Thymidine incorporation and 45Ca2+ uptake were used as endpoints. TE-85 cells cultured in the presence of 10% FBS did not exhibit a frequency dependent increase in proliferation in contrast to previous studies under growth arrested culture conditions, in which the cells were deprived of FBS. However, both TE-85 and NG108-15 cells had an increase in 45Ca2+ uptake in response to a 16 Hz 18.3 mV/cm CCEF. Fura-2 digital imaging microscopy was used to verify addition of 0.5 mM La3+ and 0.5 mM ionomycin as negative and positive controls, respectively. Imaging microscopy data was combined with 45Ca2+ incorporation results to quantify free intracellular calcium ([Ca2+]i) increase in response to CCEF exposure. TE-85 [Ca2+]i increased from 140 to 189-210 nM where as NG108-15 [Ca2+]i increased from 67 to 189-210 nM. These results suggested that serum deprivation may be a requirement for a frequency dependent increase in proliferation in TE-85 cells but is not necessary for the electric field induced increase in 45Ca2+ uptake in both TE-85 and NG108 cells. The present study also represents the first demonstration of increased 45Ca2+ uptake by neuroblastoma and/or glioma cells in response to an electric field exposure.

The effects of different steroids on costal and epiphyseal cartilage of fetal and adult rats.

The effects of different doses of various steroids on growth, and on costal and epiphyseal chondrocytes, have been studied in prenatal, immature, and adult Long-Evans rats using histochemical techniques, and both light and electron microscopy. Both prenatal and postnatal treatments have been employed. The steroids used were cortisone (CA), betamethasome (BM), and, in the prenatal group only, dexamethasone (DM). Body weight is reduced in all treated rats (except the low dose of CA) by day 17 of gestation, with greater weight reductions occurring in rats receiving the higher dose level of each steroid. In rats treated prenatally or neonatally, and sacrificed postnatally on days 39-43 or days 116-127, body weights, and tibial and tail lengths, are less than in correspondingly aged controls, thus showing a persistence of the effects of treatment. Costal and epiphyseal cartilages in prenatal rats show cellular, synthetic, and ultrastructural alterations induced by treatment with glucocorticoids but the responses are not necessarily comparable. Except for the low dose of DM, the higher doses of each steroid are more effective in inhibiting, or altering, growth and cellular differentiation in the developing fetuses. Surprisingly, a low dose of DM has a more devastating effect on the cells and extracellular matrix of both costal and epiphyseal cartilage, than do higher dose-levels of the various steroids. Low doses of CA and BM are also effective in inhibiting or altering growth and cellular differentiation, but their effectiveness is largely limited to 17 days of gestation. The order of effect of the various doses of the different steroids on fetal cartilage, listed in decreasing order of severity, is as follows: 0.12 DM, 0.24 DM, 0.42 BM, 50 CA, with 25 CA and 0.18 BM being approximately equal and only slightly different from control cartilages. The effect of prenatal or neonatal glucocorticoid treatment on chondrocytes is minimal in the 30-43 days, or 116-127 day, postnatal groups. In immature and adult rats, cortisone affects the chondrocytes more deleteriously than does betamethasone, and a 5.0 mg dose of CA seems to affect chondrocytes, body weight, and tibial and tail lengths more than 0.2 or 7.5 mg doses.

Effect of neonatal head X-irradiation on growth of costal and tibial cartilage in rats: a histochemical and electron microscopic study.

Long-Evans rats were exposed to a single dose of head X-irradiation (600 rads) at 2 days of age. Experimental and sham irradiated rats were sacrificed at 14, 20-21, 23, 41-45, and 70-71 days. Tibial epiphyseal width and the number of cells in the epiphyseal plate were determined. Histochemical and electron microscopic studies were carried out on both costal and epiphyseal cartilage. Histochemical techniques revealed a reduction in chondroitin sulfate at 14 days in both costal and epiphyseal cartilage of X-irradiated rats. Epiphyseal cartilage demonstrated recovery subsequently, and this was followed by a normal decrease of chondroitin sulfate with increasing age, but costal cartilage did not recover. Collagen synthesis was also reduced in both costal and epiphyseal cartilage, but not as dramatically as chondroitin sulfate. Except for some electron dense cells and reduced scalloping of the cell membrane, costal chondrocytes from irradiated rats did not show major ultrastructural alterations. In contrast, epiphyseal chondrocytes demonstrated radiation induced alterations in organelles, in enhanced glycogen deposition, and in retardation of chondrocyte maturation. Extracellularly in both costal and epiphyseal cartilage of irradiated rats, collagen density and matrix granules were reduced, while calcification of the matrix was enhanced. Beyond 45 days, the effects of irradiation were markedly reduced. Comparisons of the histochemical results with metabolic studies carried out previously in cartilage from the same animals indicated a more direct concordance of the histochemical results with the pattern of physical growth and supported the usefulness of morphologic and histochemical techniques in the analysis of the growth disorder in the head-irradiated rat.