Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

[Contribution of a hospital pharmacy team to critical care of patients infected with SARS-CoV-2]. / Contribution d'une équipe de pharmacie hospitalière à la prise en charge en réanimation des patients infectés par le SARS-CoV-2.

With regard to the hospital drug supply chain, the safest system is the individual automated drug dispensing one provided by the pharmacy. For several years we have been trying to convince hospital decision-makers to set it up. In the meantime, to mitigate the risks of medication errors incurred by patients and caregivers, we have set up several work teams within the care units. These teams, made up of one pharmacist and one or two hospital pharmacy technicians, who notably manage the medicine cabinets in care units. The close collaboration with doctors and nurses developed over the years was a determining factor when it became necessary to provide the newly created additional intensive care units with drugs and medical devices (MDs) in order to cope with the crisis triggered by the SARS-CoV-2 epidemic. Daily monitoring of the drugs consumed by each patient, particularly neuromuscular blocking agents and MDs was a key element in managing stocks and anticipating changes of drugs, packaging and/or devices references. These facts give weight to the Claris report published in France which recognizes that the interactions of pharmacy technicians and pharmacists in the care units have positive effects in terms of quality and safety of patient care. They highlight the dangers to which patients and caregivers are exposed on Saturdays, Sundays and holidays when the pharmacy is closed. They legitimize the question of extending the opening of the pharmacy with a full team 365 days a year.

Onboard wake vortex localization with a coherent 1.5 µm Doppler LIDAR for aircraft in formation flight configuration.

An onboard LIght Detection And Ranging (LIDAR) sensor designed to track wake vortex created by aircraft in formation flight is presented. It uses short pulses (75 ns) to obtain a spatial resolution of ∼22.5 m required to resolve small-scale structures of vortices and a blind zone of 17.5 m to locate vortices next to the wing tip. Monte Carlo simulations show that vortex centers could be located within ±0.5 m. Flight tests were performed with two aircraft in formation flight configuration. The LIDAR, installed in the following aircraft, was able to measure, in real time (every 6 s), the air flow velocities induced by the vortices created by the leading aircraft. The software was used to determine the vortex centers. These measurements were coupled to global positioning system (GPS) measurements of the two aircraft positions to determine the falling velocity of the vortices and infer their circulations.

Prognosis of Lymphoma in Patients With Known Inflammatory Bowel Disease: A French Multicentre Cohort Study.

BACKGROUND AND AIMS: The prognosis of lymphoma that occurs in patients with inflammatory bowel disease [IBD] is poorly known. METHODS: A multicentre retrospective cohort analysis was done in seven French tertiary centres from 1999 to 2019. Only lymphoma occurring in patients with previous established diagnosis of IBD were analysed. The primary outcome was progression-free survival at 3 years. RESULTS: A total of 52 patients [male 65%, Crohn's disease 79%, median age 48.3 years, median duration of IBD 10.1 years] were included, of whom 37 had been previously exposed to immunosuppressants and/or biologics for at least 3 months and 20 had primary intestinal lymphomas. The lymphoma histological types were: diffuse large B cell lymphomas [N = 17], Hodgkin lymphomas [N = 17], indolent B cell lymphomas [N = 12], and others including T cell lymphomas, mantle cell lymphomas, and unclassifiable B cell lymphoma [N = 6]. The median follow-up after lymphoma was 5.1 years (interquartile range [IQR] 4-7.8). Progression-free survival at 3 years was 85% in the overall population (95% confidence interval [CI] 75%-96%) with no significant difference between the exposed and unexposed group, 79% for patients exposed to immunosuppressants and/or biologics [95% CI 67%-94%], and 83% for patients diagnosed with primary intestinal lymphoma [95% CI 67%-100%]. No relapse of IBD has been observed during chemotherapy. The IBD relapse rate at the end of the last chemotherapy cycle was 23% at 3 years [95% CI 11%-39%] in the overall population. CONCLUSIONS: In this large cohort, the prognosis for lymphomas occurring in IBD appears to be good and similar to what is expected, irrespective of the exposure to biologics and/or immunosuppressants.

From hepatitis C virus infection to B-cell lymphoma.

In addition to liver disorders, hepatitis C virus (HCV) is also associated with extrahepatic immune manifestations and B-cell non-Hodgkin lymphoma (NHL), especially marginal zone lymphoma, de novo or transformed diffuse large B-cell lymphoma and to a lesser extent, follicular lymphoma. Epidemiological data and clinical observations argue for an association between HCV and lymphoproliferative disorders. The causative role of HCV in NHL has been further supported by the response to antiviral therapy. Pathophysiological processes at stake leading from HCV infection to overt lymphoma still need to be further elucidated. Based on reported biological studies, several mechanisms of transformation seem however to emerge. A strong body of evidence supports the hypothesis of an indirect transformation mechanism by which sustained antigenic stimulation leads from oligoclonal to monoclonal expansion and sometimes to frank lymphoma, mostly of marginal zone subtype. By infecting lymphocytes, HCV could play a direct role in cellular transformation, particularly in de novo large B-cell lymphoma. Finally, HCV is associated with follicular lymphoma in a subset of patients. In this setting, it may be hypothesized that inflammatory cytokines stimulate proliferation and transformation of IgH-BCL2 clones that are increased during chronic HCV infection. Unraveling the pathogenesis of HCV-related B-cell lymphoproliferation is of prime importance to optimize therapeutic strategies, especially with the recent development of new direct-acting antiviral drugs.

Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group.

Background: Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome. Patients and methods: The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed. Results: The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit. Conclusion(s): This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.

Interface Engineering to Create a Strong Spin Filter Contact to Silicon.

Integrating epitaxial and ferromagnetic Europium Oxide (EuO) directly on silicon is a perfect route to enrich silicon nanotechnology with spin filter functionality. To date, the inherent chemical reactivity between EuO and Si has prevented a heteroepitaxial integration without significant contaminations of the interface with Eu silicides and Si oxides. We present a solution to this long-standing problem by applying two complementary passivation techniques for the reactive EuO/Si interface: (i) an in situ hydrogen-Si (001) passivation and (ii) the application of oxygen-protective Eu monolayers-without using any additional buffer layers. By careful chemical depth profiling of the oxide-semiconductor interface via hard x-ray photoemission spectroscopy, we show how to systematically minimize both Eu silicide and Si oxide formation to the sub-monolayer regime-and how to ultimately interface-engineer chemically clean, heteroepitaxial and ferromagnetic EuO/Si (001) in order to create a strong spin filter contact to silicon.

[A pill to replace physical activity?]. / Une pilule pour remplacer l'activité--physique?

A recent study has identified two molecules able to transform white adipose tissue ("bad fat", responsible for excess weight) in brown adipose tissue ("good fat", consuming energy), bringing new hope for the treatment of obesity and diabetes. But the authors' announcement (more humorous than scientific) declaring that the study is thefirst step toward a pill that can replace the treadmill is inappropriate. It underscores the importance of employing preventive methods such as physical activity, whose benefits on health are well documented and which represents the best medicine available. Different means and tools are described in this article in order to improve the amount and quality of physical activity prescription in primary care.

Clinical spectrum of urine cultures positive for ESBL-producing Escherichia coli in hospitalized patients and impact on antibiotic use.

OBJECTIVE: We wanted to describe the clinical features associated with urinalysis positive for ESBL-producing Escherichia coli and their impact on antibiotic use. METHODS: We performed a prospective observational study in 13 French hospitals of the Paris area for 3 consecutive months. We included all patients with urine cultures positive for ESBL-producing E. coli. RESULTS: One hundred and seventeen of the 218 patients (54%) presented with asymptomatic bacteriuria, 31 (14%) with cystitis, and 70 (32%) with a parenchymal infection. Nineteen patients with asymptomatic bacteriuria (16%) received antibiotics. Forty-one with parenchymal infections (59%) received a carbapenem. A carbapenem alternative could have been used in every patient treated with a carbapenem, according to antibiotic susceptibility testing results. CONCLUSIONS: Urinary tract infections accounted for 46% of E. coli ESBL positive urinalysis. Fifty percent of parenchymal infections were treated with a carbapenem.

[Return to sport after anterior cruciate ligament reconstruction]. / Retour au sport après reconstruction du ligament croisé antérieur.

Despite continuous advances in techniques for anterior cruciate ligament reconstruction (ACLR), return to play (RTP) after surgery remains a challenge. More than one-third of the patients are unable to return to their preinjury sport level, for most because of a fear to sustain another injury. And when a RTP is attempted, up to 20% will tear their graft and a similar % will sustain an ACL tear on the opposite side. We believe that these failures result from an incomplete recovery. Based on a literature review and on our experience, we suggest 6 objective criteria to allow a safer RTP. They rely on laxity, strength, neuromuscular function, and psychological evaluations. Rehabilitation after ACLR should focus on the deficits identified by these tests and on they specific needs of the sport that the athlete plans to return to.

Polyoxometalate-stabilized, water dispersible Fe2Pt magnetic nanoparticles.

Magnetic Fe2Pt core-shell nanoparticles with 2 nm cores were synthesized with a monolayer coating of silicotungstate Keggin clusters. The core-shell composition is substantiated by structural analysis performed using high-resolution scanning transmission electron microscopy (HR-STEM) and small angle X-ray scattering (SAXS) in a liquid suspension. The molecular metal oxide cluster shell introduces an enhanced dispersibility of the magnetic Fe-Pt core-shell nanoparticles in aqueous media and thereby opens up new routes to nanoparticle bio-functionalization, for example, using pre-functionalized polyoxometalates.

Intragenic rearrangements in LARGE and POMGNT1 genes in severe dystroglycanopathies.

Dystroglycanopathies are a heterogeneous group of muscular dystrophies with autosomal recessive inheritance characterized by abnormal glycosylation of alpha-dystroglycan. The most severe phenotypes are Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease (MEB) presenting with lissencephaly type II (LIS II) and in which muscular dystrophy is associated with mental retardation and eye abnormalities. To date, six distinct genes, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE and recently in one case DPM3, have been shown to be involved in dystroglycanopathies. Genomic sequencing alone is still frequently used for diagnosis purpose, not allowing detection of intragenic rearrangements at the heterozygous state contrarily to RNA analysis, quantitative PCR and CGH array analysis. These latter methods enabled us to identify four new intragenic rearrangements in the LARGE gene in three fetuses with WWS, born to two unrelated families: deletion of exons 9-10 and duplication of introns 1-4 for the first family and deletion of exons 4 and 7 for the second one; and a deletion of the last six exons of the POMGNT1 gene in two unrelated MEB patients. Genomic dosage studies using emerging tools such as CGH array should be included in routine molecular analysis of dystroglycanopathies, not only for the screening of the LARGE gene in which this kind of mutation seems to be more frequent than point mutations, but also for the other involved genes, especially in severe clinical cases.

[Hospital infection control--beyond the hospital]. / Hygiène hospitatière--au-delà de l'hôpital.

Health care related infections are expensive untoward events, not only in terms of morbidity and mortality, but also cost. Prevention is essential, as well as limiting dissemination. Specify measures refer usually to hospital hygiene. However, health care tend to be provided more and more outside of the acute care hospital, with increasing complexity and thus risk for health care related infections. This risk varies according to patient's characteristics as well as environmental parameters. Consequently, it is essential to adapt preventive measures to situations such as home health care or nursing homes. We describe a model of regional organization for infection control in various health care settings.

Restoration of thiamine status with white or whole wheat bread in a thiamine-depleted rat model.

Long-term thiamine deficiency has been largely documented, whilst little is known about effects of short-term depletion/repletion periods on thiamine vitamers status. Rats were submitted to short-term depletion (8 days) followed by different durations of repletion (3 or 14 days) with thiamine from bread (whole wheat bread or white bread, whole B and white B respectively) or corresponding controls. Short-term depletion drastically decreased plasma thiamine (-97%) and its urinary excretion (-77%). TDP (thiamine diphosphate) was strongly affected in liver (-67%) but less affected in cerebellum (-38%) or kidneys (-45%). Short-term repletion (3 days) with whole B diet or its control restored TDP at initial values in cerebellum and kidneys. A longer repletion (14 days) was required to restore liver TDP. Comparison of the diet groups indicates that thiamine status in tissues of rat fed whole B or white B diet was comparable to that of rats fed purified thiamine. Plasma thiamine concentration could not be restored at initial values in the bread groups or respective controls. In conclusion, thiamine in whole wheat bread appears effective in preventing marginal deficiencies and plasma thiamine is a less reliable indicator of thiamine status than tissue TDP levels.

Regulation of transpirational water loss in Quercus suber trees in a Mediterranean-type ecosystem.

Sap flux density in branches, leaf transpiration, stomatal conductance and leaf water potentials were measured in 16-year-old Quercus suber L. trees growing in a plantation in southern Portugal to understand how evergreen Mediterranean trees regulate water loss during summer drought. Leaf specific hydraulic conductance and leaf gas exchange were monitored during the progressive summer drought to establish how changes along the hydraulic pathway influence shoot responses. As soil water became limiting, leaf water potential, stomatal conductance and leaf transpiration declined significantly. Predawn leaf water potential reflected soil water potential measured at 1-m depth in the rhizospheres of most trees. The lowest predawn leaf water potential recorded during this period was -1.8 MPa. Mean maximum stomatal conductance declined from 300 to 50 mmol m(-2) s(-1), reducing transpiration from 6 to 2 mmol m(-2) s(-1). Changes in leaf gas exchange were attributed to reduced soil water availability, increased resistances along the hydraulic pathway and, hence, reduced leaf water supply. There was a strong coupling between changes in soil water content and stomatal conductance as well as between stomatal conductance and leaf specific hydraulic conductance. Despite significant seasonal differences among trees in predawn leaf water potential, stomatal conductance, leaf transpiration and leaf specific hydraulic conductance, there were no differences in midday leaf water potentials. The strong regulation of changes in leaf water potential in Q. suber both diurnally and seasonally is achieved through stomatal closure, which is sensitive to changes in both liquid and vapor phase conductance. This sensitivity allows for optimization of carbon and water resource use without compromising the root-shoot hydraulic link.

Water-use strategies in two co-occurring Mediterranean evergreen oaks: surviving the summer drought.

In the Mediterranean evergreen oak woodlands of southern Portugal, the main tree species are Quercus ilex ssp. rotundifolia Lam. (holm oak) and Quercus suber L. (cork oak). We studied a savannah-type woodland where these species coexist, with the aim of better understanding the mechanisms of tree adaptation to seasonal drought. In both species, seasonal variations in transpiration and predawn leaf water potential showed a maximum in spring followed by a decline through the rainless summer and a recovery with autumn rainfall. Although the observed decrease in predawn leaf water potential in summer indicates soil water depletion, trees maintained transpiration rates above 0.7 mm day(-1) during the summer drought. By that time, more than 70% of the transpired water was being taken from groundwater sources. The daily fluctuations in soil water content suggest that some root uptake of groundwater was mediated through the upper soil layers by hydraulic lift. During the dry season, Q. ilex maintained higher predawn leaf water potentials, canopy conductances and transpiration rates than Q. suber. The higher water status of Q. ilex was likely associated with their deeper root systems compared with Q. suber. Whole-tree hydraulic conductance and minimum midday leaf water potential were lower in Q. ilex, indicating that Q. ilex was more tolerant to drought than Q. suber. Overall, Q. ilex seemed to have more effective drought avoidance and drought tolerance mechanisms than Q. suber.

The bioavailability of polyphenols is highly governed by the capacity of the intestine and of the liver to secrete conjugated metabolites.

BACKGROUND: After ingestion of a complex meal containing foods and beverages of plant origin, different polyphenols are likely to be simultaneously present in the intestine. However, almost nothing is known about their interactions and possible consequences on their bioavailability. AIM OF THE STUDY: The present study deals with the intestinal absorption and splanchnic metabolism of three polyphenols, genistein, hesperetin and ferulic acid (FA),when perfused in the small intestine alone or in combination, at different doses (15 and 120 microM). METHODS: The fate of polyphenols in the small intestine was studied using a rat in situ intestinal perfusion model. Polyphenols were analysed in perfusate, bile and plasma by HPLC. RESULTS: Whatever the perfused dose, the efficiency of the net transfer towards the enterocyte was similar for the three polyphenols and not significantly modified by any association between these molecules. However, FA largely differed from the two flavonoids by its low intestinal secretion of conjugates. When perfused at 15 microM, the secretion of conjugates back to the lumen represented 6.2% of the net transfer into the enterocytes for FA compared to 25.5 and 20 % for genistein and hesperetin respectively. Intestinal conjugation and secretion of conjugates back to the gut lumen varied with the dose of flavonoids: saturation of conjugation was observed for the highest dose or when a high dose of a second flavonoid was perfused simultaneously. Intensity of the biliary secretion substantially differed among tested polyphenols: 7.7% of the net transfer for FA vs 50% for genistein or hesperetin. The extent of the enterohepatic cycling of these polyphenols was proportional to the perfused dose and unaffected by the simultaneous presence of different compounds in the intestine. CONCLUSION: Genistein and hesperetin appeared less available than FA for peripheral tissues because of a high intestinal and biliary secretion of their conjugates. Moreover, data suggest that a high polyphenol intake may improve their bioavailability due to saturation of the intestinal secretion of conjugates.

[Fibular tendon dislocations associated with calcaneal fractures: four case reports]. / Fractures du calcanéus avec luxation des tendons fibulaires. A propos de 4 cas.

We report four cases of traumatic dislocation of the fibular tendons associated with calcaneal fractures. There are few reports of this type of association in the literature. We analyzed the diagnostic and therapeutic features. Two patients with a history of calcaneal fracture presented old, unrecognized, symptomatic dislocations of the fibular tendons. After CT confirmation, the tendons were repositioned surgically. During the last two years, CT scans performed systematically in patients with calcaneal fracture led to the discovery of two recent dislocations associated with calcaneal fractures. In these patients the fibular tendon dislocation was treated during the osteosynthesis procedure by relocating the tendon in the gutter and reinsertion of the retinaculum. The two older cases illustrated the serious functional consequences of neglecting displaced fibular tendons. We also detailed the characteristic CT signs observed with the two recent cases. The association of calcaneal fracture with fibular tendon displacement is rarely reported in the literature, but is not exceptional. Physical examination is limited during the acute phase. Imaging, particularly CT is required to demonstrate the tendon displacement. The objective results of surgical treatment were good. Orthopedic treatment is almost always unsuccessful. The association of fibular tendon displacement with calcaneal fracture is not exceptional. We have instituted a standardized CT protocol for all cases of calcaneal fracture in order to recognize disinsertion of the retinaculum and enable treatment at the same time as the osteosynthesis.

Determination of thiamine and its phosphate esters in rat tissues analyzed as thiochromes on a RP-amide C16 column.

A new reversed-phase chromatographic method is described for the separation and quantification of thiamine (T), thiamine monophosphate (TMP) and diphosphate (TDP) in rat tissues. Sample extraction with perchloric acid (HClO(4)) was found more suitable than extraction with trichloroacetic acid (TCA), as regards convenience and background fluorescence. Derivatization of thiamine vitamers to thiochromes was optimized and complete separation of TDP and TMP thiochromes was obtained on a RP-amide C16 column in isocratic elution, with T thiochrome eluting in less than 10 min. The precision and the accuracy of the HPLC procedure were assessed: ranging from 0.5 to 7.7% for intra-day and from 2.0 to 9.4% for inter-day precision, a recovery average of 101% was determined (range 90-111%). Mean values of recovery for TDP, TMP or T were 91, 96 and 90% for liver extracts, respectively. Analysis of vitamers in tissues of rat submitted to 8 days thiamin deficiency, followed by a 14 days repletion, showed a significant reduction of TPP after 8 days of depletion in liver (-67%), brains (-50%), kidneys (-60%), followed by a complete recovery upon repletion.

Bioavailability of phloretin and phloridzin in rats.

Phloretin is a flavonoid found exclusively in apples and in apple-derived products where it is present as the glucosidic form, namely, phloridzin (phloretin 2'-O-glucose). In the present study, we compared the changes in plasma and urine concentrations of these two compounds in rats fed a single meal containing 0.25% phloridzin or 0.157% phloretin (corresponding to the ingestion of 22 mg of phloretin equivalents). In plasma, phloretin was recovered mainly as the conjugated forms (glucuronided and/or sulfated) but some unconjugated phloretin was also detected. By contrast, no trace of intact phloridzin was detected in plasma of rats fed a phloridzin meal. These compounds presented different kinetics of absorption; phloretin appeared more rapidly in plasma when rats were fed the aglycone than when fed the glucoside. However, whatever compound was administered, no significant difference in the plasma concentrations of total phloretin were observed 10 h after food intake. At 24 h after the beginning of the meal, the plasma concentrations of phloretin were almost back to the baseline, indicating that this compound was excreted rapidly in urine. The total urinary excretion rate of phloretin was not affected by the forms administered, and was estimated to be 8.5 micromol/24 h in rats fed phloretin or phloridzin. Thus, 10.4% of the ingested dose was recovered in urine after 24 h.