Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT.

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.

Influenza at the animal-human interface: a review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1).

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of t he World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype descending from North American and Eurasian SIV lineages and various reassortants thereof. Direct exposure to birds or swine was the most likely source of infection for the cases with available information on exposure.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Model and Empirical Data-Based Cost-Utility Studies of Continuous Glucose Monitoring in Individuals with Type 1 Diabetes: A Protocol of a Systematic Review on Methodology and Quality.

INTRODUCTION: This review aims to critically appraise differences in methodology and quality of model-based and empirical-data-based cost-utility studies to address key limitations, opportunities, and challenges to inform future cost-utility analyses of continuous glucose monitoring (CGM) in type 1 diabetes. This protocol is registered at PROSPERO (CRD42023391284). METHODS: The review will be conducted in accordance with the PRISMA guideline for systematic reviews. Searches will be conducted in MEDLINE, Embase, Web of Science, Cochrane Library, and Econlit from 2000 to January 2023. Model and empirical data-based studies evaluating the cost-utility of any CGM system in type 1 diabetes will be considered for inclusion. Studies that only report on cost per life year or any other clinical outcome, or reporting only costs or only clinical outcomes studies in type 2 diabetes populations, and studies on bi-hormonal closed loops and do-it-yourself hybrid closed loop devices will be excluded. Two reviewers will independently screen each study for inclusion. Data on the intervention, population, model settings (such as perspective, time horizon), model type and structure, clinical outcomes used to populate the model, validation, and uncertainty will be extracted and qualitatively synthesised. Quality will be assessed using the Philips et al. 2006 (model-based studies) or Consensus Health Economic Criteria (empirical data-based studies) checklists. Model validation will be assessed using the AdViSHE checklist. DISCUSSION: Now that CGM is being used more broadly in practice, critical appraisal of existing cost-utility methodology and quality is important to inform future cost-utility analyses of CGM in type 1 diabetes in various settings.

Time course and risk factors of post-stroke fatigue: a prospective cohort study.

BACKGROUND: Post-stroke fatigue (PSF) often occurs after stroke and has a negative impact on the rehabilitation process. Several studies focused either on short- or on long-term PSF and their relations with stroke characteristics. However, possible pre-stroke risk factors such as history of depression, pre-existent white matter lesions or brain atrophy were usually not taken into account. Therefore, the precise mechanisms underlying PSF remain still unclear. This study was aimed at assessing the possible contributions of (pre-)stroke factors to both short-term PSF and its course over time. METHODS: This study pertains to 108 patients with an acute cerebral infarction. PSF was rated by the Checklist Individual Strength at 2 months and 1.5 year post-stroke. The relation between (pre-)stroke factors and PSF was assessed with multivariate regression analysis. RESULTS: The prevalence of baseline PSF was 35% and at follow-up 33%. Older age had a protective effect on PSF at baseline (OR 0.95; 95% CI 0.91-0.98), whereas post-stroke depressive symptoms and infratentorial infarctions were related to an increased risk for PSF (OR 1.40; 95% CI 1.21-1.63 and OR 4.69; 95% CI 1.03-21.47, respectively). Baseline fatigue was related to an increased risk of PSF at follow-up (OR 1.15; 95% CI 1.09-1.22). CONCLUSIONS: Predictors for baseline fatigue were younger age, post-stroke depressive symptoms, and infratentorial infarctions. Baseline fatigue did predict fatigue outcome over time, suggesting that early interventions might be useful to prevent deteriorated PSF.

Highly heterogeneous temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates, northern France.

We assayed the temperature sensitivity of 2009 pandemic influenza A(H1N1) viral isolates (n=23) and seasonal influenza A(H1N1) viruses (n=18) isolated in northern France in 2007/08 and 2008/09. All isolates replicated with a similar efficiency at 34 °C and 37 °C, and with a lower efficiency at 40 °C. The pandemic viral isolates showed a stronger heterogeneity in their ability to grow at the highest temperature, as compared with the seasonal isolates. No statistically significant difference in temperature sensitivity was observed between the pandemic viral isolates from severe and mild cases of influenza. Our data point to the impact of temperature sensitivity on the genetic evolution and diversification of the pandemic influenza A(H1N1) virus since its introduction into the human population in April 2009, and call for close surveillance of this phenotypic marker related to host and tissue tropism.

S-OtrH3N2 viruses: use of sequence data for description of the molecular characteristics of the viruses and their relatedness to previously circulating H3N2 human viruses.

Emergence of influenza viruses from the animal reservoir is a permanent challenge. The rapid description and immediate sharing of information on these viruses is invaluable for influenza surveillance networks and for pandemic preparedness. With the help of data generated from the World Health Organization Collaborating Centre for Reference and Research on Influenza at the United States Centers for Disease Control and Prevention, we provide here information on the swine­origin triple reassortant influenza A(H3N2) viruses detected in human cases in the north-east of the United States.

Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.

COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models.

One year into the Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), effective treatments are still needed 1-3 . Monoclonal antibodies, given alone or as part of a therapeutic cocktail, have shown promising results in patients, raising the hope that they could play an important role in preventing clinical deterioration in severely ill or in exposed, high risk individuals 4-6 . Here, we evaluated the prophylactic and therapeutic effect of COVA1-18 in vivo , a neutralizing antibody isolated from a convalescent patient 7 and highly potent against the B.1.1.7. isolate 8,9 . In both prophylactic and therapeutic settings, SARS-CoV-2 remained undetectable in the lungs of COVA1-18 treated hACE2 mice. Therapeutic treatment also caused a dramatic reduction in viral loads in the lungs of Syrian hamsters. When administered at 10 mg kg - 1 one day prior to a high dose SARS-CoV-2 challenge in cynomolgus macaques, COVA1-18 had a very strong antiviral activity in the upper respiratory compartments with an estimated reduction in viral infectivity of more than 95%, and prevented lymphopenia and extensive lung lesions. Modelling and experimental findings demonstrate that COVA1-18 has a strong antiviral activity in three different preclinical models and could be a valuable candidate for further clinical evaluation.

A poliovirus neutralization epitope expressed on hybrid hepatitis B surface antigen particles.

The hepatitis B virus (HBV) envelope protein carrying the surface antigen (HBsAg) is assembled with cellular lipids in mammalian cells into empty viral envelopes. In a study to evaluate the capacity of such particles to present foreign peptide sequences in a biologically active form, in-phase insertions were created in the S gene encoding the major envelope protein. One of the sequences inserted was a synthetic DNA fragment encoding a poliovirus neutralization epitope. Mammalian cells expressing the modified gene secreted hybrid particles closely resembling authentic 22-nanometer HBsAg particles. These particles reacted with a poliovirus-specific monoclonal antibody and induced neutralizing antibodies against poliovirus. The results indicate that empty viral envelopes of HBV may provide a means for the presentation of peptide sequences and for their export from mammalian cells.

Baseline characteristics and clinical symptoms related to respiratory viruses identified among patients presenting with influenza-like illness in primary care.

OBJECTIVES: We aimed to identify patients' clinical characteristics associated with respiratory viruses identified among patients presenting with influenza-like illness (ILI). METHODS: A sample of patients of all ages presenting with ILI was included by physicians of the French Sentinelles network during two seasons (2015/16 and 2016/17). Nasopharyngeal samples were tested for the presence of influenza virus (IV), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (HMPV). Patients' characteristics associated with each of the four virus classes were studied using multivariate logistic regressions. RESULTS: A total of 5859 individuals were included in the study: 48.0% tested positive for IV, 7.9% for HRV, 7.5% for RSV and 4.1% for HMPV. Cough was associated with IV (OR 2.14, 95% CI 1.81-2.52) RSV (OR 2.52, 95% CI 1.75-3.74) and HMPV detection (OR 2.15, 95% CI 1.40-3.45). Rhinorrhoea was associated mainly with HRV detection (OR 1.75, 95% CI 1.34-2.32). Headache was associated with IV detection (OR 1.75, 95% CI 1.34-2.32), whereas absence of headache was associated with RSV and HMPV detection. Dyspnoea was associated with RSV detection (OR 2.33, 95% CI 1.73-3.12) and absence of dyspnoea with IV detection. Conjunctivitis was associated with IV detection (OR 1.27, 95% CI 1.08-1.50). Some associations were observed only in children: dyspnoea and cough with RSV detection (age <5 years), conjunctivitis with IV detection (age <15 years). Period of onset of symptoms differed among aetiological diagnoses. Seasonal influenza vaccination decreased the risk of IV detection (OR, 0.67, 95% CI 0.51-0.86). CONCLUSIONS: This study allowed the identification of symptoms associated with several viral aetiologies in patients with ILI. A proper knowledge and understanding of these clinical signs may improve the medical management of patients.

Early prediction of favourable recovery 6 months after mild traumatic brain injury.

BACKGROUND: Predicting outcome after mild traumatic brain injury (MTBI) is notoriously difficult. Although it is recognised that milder head injuries do not necessarily mean better outcomes, less is known about the factors that do enable early identification of patients who are likely to recover well. OBJECTIVE: To develop and internally validate two prediction rules for identifying patients who have the highest chance for good 6 month recovery. METHODS: A prospective cohort study was conducted among patients with MTBI admitted to the emergency department. Apart from MTBI severity indices, a range of pre-, peri- and early post-injury variables were considered as potential predictors, including emotional and physical functioning. Logistic regression modelling was used to predict the absence of postconcussional symptoms (PCS) and full return to work (RTW). RESULTS: At follow-up, 64% of the 201 participating patients reported full recovery. Based on our prediction rules, patients without premorbid physical problems, low levels of PCS and post-traumatic stress early after injury had a 90% chance of remaining free of PCS. Patients with over 11 years of education, without nausea or vomiting on admission, with no additional extracranial injuries and only low levels of pain early after injury had a 90% chance of full RTW. The discriminative ability of the prediction models was satisfactory, with an area under the curve >0.70 after correction for optimism. CONCLUSIONS: Early identification of patients with MTBI who are likely to have good 6 month recovery was feasible on the basis of relatively simple prognostic models. A score chart was derived from the models to facilitate clinical application.

[A young woman from Cameroon with rectal blood loss, intestinal schistosomiasis and rectosigmoid carcinoma]. / Een jonge vrouw uit kameroen met rectaal bloedverlies, intestinale schistosomiasis en rectosigmoïdcarcinoom.

A 32-year-old woman from Cameroon presented with rectal blood loss due to a focally infiltrating adenocarcinoma of the rectosigmoid in the presence of an active intestinal schistosomiasis (Schistosoma intercalatum). A correlation between chronic intestinal schistosomiasis and the development of colorectal cancer has been suggested in the literature, but is not uniformly accepted. However, the case presented here reinforces this suggestion. In a patient with rectal blood loss who comes from an area where intestinal schistosomiasis is endemic, the possibility of a colorectal carcinoma should be considered in the diagnosis.

Influenza B burden during seasonal influenza epidemics in France.

CONTEXT: Seasonal flu outbreaks are linked to the circulation of influenza virus type A or B. Special attention has always been paid to influenza A epidemics; but recently, several studies have investigated the impact of influenza B virus epidemics, particularly as, since the 1980s, two antigenically different influenza B lineages co-circulate, raising the issue of vaccine matching. OBJECTIVES: We present the results of influenza B burden during nine influenza seasons (2003-2013) and vaccine matching of the circulating lineages. PATIENTS AND METHODS: Clinical and virological influenza surveillance data, collected by the Regional Groups for Influenza Surveillance Network in France, allows for studying the burden of influenza in the practice of the population of ambulatory care physicians. RESULTS AND CONCLUSION: Our analysis is based on 37,801 samples, of which 12,036 were virologically confirmed influenza cases (31.8%), including 3576 cases of influenza B (29.7% of influenza cases). Influenza B viruses significantly circulated during six seasons. For each season, the influenza B epidemic peaked later than the influenza A epidemic. Influenza B is very common in children of school age but also affects other age groups. Finally, more than one-third of the analyzed influenza B viruses belonged to a different lineage than the one used in the composition of the trivalent vaccine. Our results are comparable to those described in other countries.

The EBMT-ELN working group recommendations on the prophylaxis and treatment of GvHD: a change-control analysis.

In 2013, recommendations for a standardized practice in the prophylaxis and treatment of GvHD were adopted and published by the European Society for Blood and Marrow Transplantation and the European LeukemiaNet. One year later, all 341 European Society for Blood and Marrow Transplantation centres performing allogeneic haematopoietic stem cell transplantation were contacted for a change-control analysis and asked to fill in a questionnaire; 111 centres (33%) responded. Of these, 83% had been aware of the recommendations. Paediatric centres (P=0.004), centres with shorter programme duration (P=0.049), not JACIE (the Joint Accreditation Committee of the International Society for Cellular Therapy and the European Society for Blood and Marrow Transplantation)-accredited centres (P=0.010) and centres from middle-income countries (P=0.033) were more likely to be unaware of the recommendations. Thirty-eight per cent of the centres regarded the recommendations as relevant guidelines affecting their policies, 61% as interesting information. Thirty per cent had decided to make changes in their institutional protocols based on the recommendations. More than 80% were willing to use the recommendations for a control arm in randomized studies. This survey shows that the published recommendations had some, though insufficient, impact on the strategies and methods of allogeneic haematopoietic stem cell transplantation applied by the centres. It also identified some of the weaknesses to be addressed when releasing recommendations in the future.

[Research and development of reverse genetics for influenza viruses]. / Développement et applications de la génétique inverse des virus grippaux.

Influenza viruses have long been refractory to reconstitution from cloned cDNAs, likely because of the properties of their genome : segmented and negative-stranded RNA, infectious only if in association with the nucleoprotein and polymerase complex. In the late 90s, by relying on an RNA polymerase I dependent transcription system and by cotransfecting 12 or 8 plasmids, reconstitution of the eight ribonucleoproteins of an influenza A virus in a cell was achieved, and production of recombinant viruses was finally obtained. Plasmidbased reverse genetics systems are now widely used to study the molecular mechanisms of virus replication and pathogenicity. They are also proving very useful in the field of vaccinology, as they allow the conception of pandemic vaccines as well as new types of attenuated live vaccines. They could also lead to the use of recombinant influenza viruses as gene delivery vehicles, for prophylactic or therapeutic purposes.

Nonulcer dyspepsia in a Dutch working population and Helicobacter pylori. Ulcer history as an explanation of an apparent association.

BACKGROUND: There is considerable debate about whether Helicobacter pylori infection is important in causing nonulcer dyspepsia. Many studies assessing this relationship have been performed in selected patient populations and included patients with a history of peptic ulcer. General population-based data with attention to ulcer history are needed to clarify this relationship. METHODS: A questionnaire on ulcer history and dyspeptic symptoms during the preceding 3-month period was obtained from apparently healthy employees who underwent a periodic medical examination in the Netherlands. In addition, serum samples were analyzed for anti-H pylori IgG antibodies. RESULTS: A total of 427 men and 73 women, aged 22 to 69 years, participated in the study. None of the women but 27 men (6%) had a previous diagnosis of peptic ulcer. Among 19 unoperated-on men with verified duodenal (17 subjects) and gastric (two subjects) ulcer, 89% were H pylori positive, while 74% had frequent dyspeptic symptoms in the 3 months before the study. Among the 400 men and 73 women without an ulcer history, the 3-month period prevalence of frequent dyspepsia was 13% and 21%, respectively. The rate of H pylori positivity was 25% in subjects with nonulcer dyspepsia and 29% in all others. The H pylori infection rate increased with age and with a lower occupational level but was independent of gender. In the male population, various differences in symptoms between H pylori-positive and H pylori-negative subjects could be detected when the 27 subjects with a history of ulcer were included, whereas these differences disappeared when these subjects were excluded. CONCLUSIONS: In the Dutch working population, nonulcer dyspepsia is not related to H pylori infection, whereas for duodenal ulcer the relationship is clear. The apparent association between dyspeptic symptoms and H pylori infection is entirely accounted for by subjects with an ulcer history.

[General practice and surveillance: the example of influenza in France]. / Médecin généraliste et veille sanitaire: l'exemple de la grippe en France.

UNLABELLED: Data registration by the GROG national network (Regional Group for the Surveillance of Influenza) since 1984 has helped to identify methodological problems. The choice of sentinels and the selection of indicators depend on the analysis of actual influenza consequences. Various sentinels may be concerned: health insurance companies, private companies, schools, physicians, pharmacists. Health care organization modifies the validity of indicators. In France, for instance, home visits were an excellent indicator for early warning before 1995 but this indicator is no longer as efficient as before. The virological detection of Influenza depends on the organization of transportation (samples, results). The predictive value of cases definitions depends on the incidence of infection. The level of choice between specificity and sensibility modifies the perception of outbreaks. Sentinel participation rate influences the sample representativity. The farther this rate is from 100%, the more result validity decreases (in the same way that patients lost to follow-up compromise the validity of results in clinical trials). The publication of results can modify health expenses and behaviors. CONCLUSION: The GROG network stresses the important role that general practitioners play in health surveillance; it also raises questions in the field of mathematics, statistics, professional organization, training, education, and politics.

Nuclear localization of poliovirus capsid polypeptide VP1 expressed as a fusion protein with SV40-VP1.

The poliovirus cDNA fragment coding for capsid polypeptide VP1 was inserted between the EcoRI and BamHI sites of SV40 DNA, generating a chimaeric gene in which the sequence of the 302 amino acids (aa) of poliovirus capsid polypeptide VP1 was placed downstream from that of the 94 N-terminal aa of SV40 capsid polypeptide VP1. The resulting defective, hybrid virus, SV40-delta 1 polio, was propagated in CV1 cells using an early SV40 mutant, am404, as a helper. Cells doubly infected by SV40-delta 1 polio and am404 expressed a 50-kDal fusion protein which was specifically immunoprecipitated by polyclonal and/or monoclonal antibodies raised against poliovirus capsids or against poliovirus polypeptide VP1. Examination of the infected cells by immunofluorescence after staining with anti-poliovirus VP1 immune sera revealed that the fusion protein was mostly located in the intra- and perinuclear space of the cells, in contrast to the exclusively intracytoplasmic location of genuine poliovirus VP1 polypeptide that was observed in poliovirus-infected cells. This suggests that the N-terminal part of the SV40-VP1 polypeptide could contain an important sequence element acting as a migration signal for the transport of proteins from the cytoplasm to the nucleus.