Design and implementation of the European-Mediterranean Postgraduate Programme on Organ Donation and Transplantation (EMPODaT) for Middle East/North Africa countries.

This prospective study reports the design and results obtained after the EMPODaT project implementation. This project was funded by the Tempus programme of the European Commission with the objective to implement a common postgraduate programme on organ donation and transplantation (ODT) in six selected universities from Middle East/North Africa (MENA) countries (Egypt, Lebanon and Morocco). The consortium, coordinated by the University of Barcelona, included universities from Spain, Germany, Sweden and France. The first phase of the project was to perform an analysis of the current situation in the beneficiary countries, including existing training programmes on ODT, Internet connection, digital facilities and competences, training needs, and ODT activity and accreditation requirements. A total of 90 healthcare postgraduate students participated in the 1-year training programme (30 ECTS academic credits). The methodology was based on e-learning modules and face-to-face courses in English and French. Training activities were evaluated through pre- and post-tests, self-assessment activities and evaluation charts. Quality was assessed through questionnaires and semi-structured interviews. The project results on a reproducible and innovative international postgraduate programme, improvement of knowledge, satisfaction of the participants and confirms the need on professionalizing the activity as the cornerstone to ensure organ transplantation self-sufficiency in MENA countries.

Computed tomography analysis of the relationship between the coronoid and the radial head.

BACKGROUND: The coronoid process is an important stabilizer of the elbow, and its anatomy has been extensively studied. However, data documenting the relationship of the coronoid relative to the radial head (RH) are limited. The latter is a good landmark for the surgeon when débriding or reconstructing the coronoid. This imaging-based study quantified the anatomic relationship between the coronoid and the proximal radius and ulna. METHODS: We investigated 80 cadaveric upper extremities (18 paired elbows) by 3-dimensional digital analysis of computed tomography data. After construction of a standardized coordinate system, the relationships between the coronoid, the anterior-most point of the RH, the deepest point of the articular surface of the RH, the top of the lesser sigmoid notch, and the deepest point of the guiding ridge of the trochlear notch were analyzed. RESULTS: The mean height of the tip of the coronoid was 36 ± 4 mm (range, 26-43 mm). The mean height of the anterior-most point of the RH was 40 ± 4 mm (range, 28-47 mm). The mean distance between the tip of the coronoid and the anterior-most point of the RH was 4.5 ± 1 mm (range, 2-10 mm). For paired elbows, the heights of the tip of the coronoid and the anterior-most point of the RH were similar between sides. CONCLUSION: This study described the relationship between the coronoid and RH. This information should prove useful when reconstructing a coronoid from a medial approach in the case of an intact RH. The difference in radiographic height between the tip of the coronoid and anterior RH in the normal elbow averages 5 mm. However, when we account for the normal cartilage thickness of the RH and coronoid, a 3- to 6-mm difference in height would be seen at surgery depending on whether the cartilage of the coronoid process is intact or removed. The distance between the tip of the coronoid and the anterior-most point of the RH is similar to the size of shavers used when débriding osteophytes during arthroscopy.

Impact of Haemophilus influenzae type b vaccination on the incidence of invasive Haemophilus influenzae disease in France, 15 years after its introduction.

We assessed the impact of Haemophilus influenzae type b (Hib) vaccination, introduced in France in early 1993, on the incidence of invasive Haemophilus influenzae (Hi) disease up to 2008.The incidence of Hi meningitis fell from 0·9/100000 in 1991­1992 to 0·09/100 000 in 1996­2008,with a marked decline (96%) in children aged <5 years, including infants aged <3 months, from 12 to 0·4 /100 000. The incidence of invasive Hi disease also decreased in children aged <15 years from 6 to 0·7 /100 000, remained stable in the 15­64 years age group at about 0·5/100 000,and increased slightly from 2·0 to 2·4 /100 000 in persons aged >64 years. No emergence of non-encapsulated or encapsulated non-vaccine serotypes was observed. These findings confirm the major direct impact of Hib vaccination on the incidence of Hi invasive disease in children and the indirect benefit of vaccination for infants too young to be vaccinated.

WAO-ARIA consensus on chronic cough - Part III: Management strategies in primary and cough-specialty care. Updates in COVID-19.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Modulation of Interleukin-8 and staphylococcal flora by Avène hydrotherapy in patients suffering from chronic inflammatory dermatoses.

BACKGROUND: A number of studies argue in favour of an important role of microbial colonization, in particular of Staphylococcus aureus, in triggering atopic dermatitis (AD) flare-up and psoriasis, in particular through the superantigenic properties of toxins generated by S. aureus. OBJECTIVES: The aim of this study was to assess the efficacy of a 3-week Avène hydrotherapy on the skin surface of patients suffering from psoriasis or atopic dermatitis. METHODS: Skin samples were taken from healthy subjects or atopic (n = 18) or psoriatic patients (n = 39) undergoing hydrotherapy at Avène at the beginning (D0) and the end of treatment (D18). The severity of the dermatosis was evaluated according to SCORing Atopic Dermatitis (SCORAD) or Psoriasis Area Severity Index (PASI) scores at D0 and D18. Marker of inflammation interleukin 8 (IL-8), S. aureus colonization (protein A) and enterotoxins were assessed in skin samples using RT-PCR. RESULTS: At D0, significant differences were observed between healthy subjects and atopic or psoriatic patients in all the parameters evaluated (IL-8, protein A). At the end of the hydrotherapy, a significant decrease in SCORAD was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin D in patients with atopic dermatitis. Similarly, a significant decrease in PASI was associated with a significant reduction of IL-8, S. aureus colonization and enterotoxin N in patients with psoriasis. CONCLUSIONS: This study demonstrates the positive effects of Avène hydrotherapy on the skin of patients suffering from chronic dermatosis, with decreased inflammation and reduced colonization by S. aureus.

WAO-ARIA consensus on chronic cough - Part 1: Role of TRP channels in neurogenic inflammation of cough neuronal pathways.

BACKGROUND: Cough features a complex peripheral and central neuronal network. The function of the chemosensitive and stretch (afferent) cough receptors is well described but partly understood. It is speculated that chronic cough reflects a neurogenic inflammation of the cough reflex, which becomes hypersensitive. This is mediated by neuromediators, cytokines, inflammatory cells, and a differential expression of neuronal (chemo/stretch) receptors, such as transient receptor potential (TRP) and purinergic P2X ion channels; yet the overall interaction of these mediators in neurogenic inflammation of cough pathways remains unclear. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on neuroanatomy and pathophysiology of chronic cough. The role of TRP ion channels in pathogenic mechanisms of the hypersensitive cough reflex was also examined. OUTCOMES: Chemoreceptors are better studied in cough neuronal pathways compared to stretch receptors, likely due to their anatomical overabundance in the respiratory tract, but also their distinctive functional properties. Central pathways are important in suppressive mechanisms and behavioral/affective aspects of chronic cough. Current evidence strongly suggests neurogenic inflammation induces a hypersensitive cough reflex marked by increased expression of neuromediators, mast cells, and eosinophils, among others. TRP ion channels, mainly TRP V1/A1, are important in the pathogenesis of chronic cough due to their role in mediating chemosensitivity to various endogenous and exogenous triggers, as well as a crosstalk between neurogenic and inflammatory pathways in cough-associated airways diseases.

WAO-ARIA consensus on chronic cough - Part II: Phenotypes and mechanisms of abnormal cough presentation - Updates in COVID-19.

BACKGROUND: Chronic cough can be triggered by respiratory and non-respiratory tract illnesses originating mainly from the upper and lower airways, and the GI tract (ie, reflux). Recent findings suggest it can also be a prominent feature in obstructive sleep apnea (OSA), laryngeal hyperresponsiveness, and COVID-19. The classification of chronic cough is constantly updated but lacks clear definition. Epidemiological data on the prevalence of chronic cough are informative but highly variable. The underlying mechanism of chronic cough is a neurogenic inflammation of the cough reflex which becomes hypersensitive, thus the term hypersensitive cough reflex (HCR). A current challenge is to decipher how various infectious and inflammatory airway diseases and esophageal reflux, among others, modulate HCR. OBJECTIVES: The World Allergy Organization/Allergic Rhinitis and its Impact on Asthma (WAO/ARIA) Joint Committee on Chronic Cough reviewed the current literature on classification, epidemiology, presenting features, and mechanistic pathways of chronic cough in airway- and reflux-related cough phenotypes, OSA, and COVID-19. The interplay of cough reflex sensitivity with other pathogenic mechanisms inherent to airway and reflux-related inflammatory conditions was also analyzed. OUTCOMES: Currently, it is difficult to clearly ascertain true prevalence rates in epidemiological studies of chronic cough phenotypes. This is likely due to lack of standardized objective measures needed for cough classification and frequent coexistence of multi-organ cough origins. Notwithstanding, we emphasize the important role of HCR as a mechanistic trigger in airway- and reflux-related cough phenotypes. Other concomitant mechanisms can also modulate HCR, including type2/Th1/Th2 inflammation, presence or absence of deep inspiration-bronchoprotective reflex (lower airways), tissue remodeling, and likely cough plasticity, among others.

Methicillin-resistant Staphylococcus aureus among a network of French private-sector community-based-medical laboratories.

OBJECTIVE: The aim of this study was to estimate the frequency of methicillin-resistant Staphylococcus aureus (MRSA) strains in the French community and the proportion of Panton-Valentine (PVL)-MRSA. DESIGN: A cross-sectional study was made during a 3-month period in 2003 through a network of private-sector, community-based medical laboratories selected throughout France: the Labville network. Each MRSA isolate was included and characterized by French National Reference Center for Staphylococci. The total number of S. aureus isolates was also collected. RESULTS: Among the 283 patients infected or colonized by MRSA, 166 (59%) were considered as healthcare-associated, 14 (5%) as nursing-associated and 39 (14%) as community-acquired. The proportion of methicillin resistance among S. aureus was 14%. Taking into account the sampling design, the incidence of MRSA cases in French outpatients was estimated to be 0.50 [CI95%: 0.41-0.60] per 10,000 inhabitants. The molecular analysis confirmed that 80.6% belong to the Lyon clone, the most prevalent hospital MRSA clone spreading in France and 10.6% to a closely related clone. An emerging MRSA clone containing the tst1 gene was detected in six patients and the PVL-positive ST80 clone only in one, 22-year-old, patient. CONCLUSION: Most of MRSA cases diagnosed in the community in France, in 2003, were elderly with specific risk factors and harbored hospital strains. The prevalence of PVL-MRSA remained low.

Different effect of Toxoplasma gondii infection on adhesion capacity of fibroblasts and monocytes.

This study investigated the effect of infection with the apicomplexan parasite Toxoplasma gondii, in combination with the concomitant cytokine environment (IFN-gamma/TNF-alpha), on adhesion of THP-1 monocytic cells to MRC-5 fibroblasts. Surprisingly, infection of THP-1 cells decreased their adhesion to the MRC-5 cell monolayer. This decrease was compensated by IFN-gamma/TNF-alpha stimulation. In contrast, infection of MRC-5 cells significantly increased adhesion, which was synergistically augmented by cytokine stimulation. Levels of ICAM-1 (CD54) on MRC-5 cells, as well as LFA-1 (CD11a) on THP-1 cells, were not changed by infection, neither in resting, nor in cytokine stimulated cells. These results show that T. gondii infection alters adhesion properties and reactivity to cytokine stimulation in a cell-specific way.

Molecular characterization of inflammation and Staphylococcus aureus colonization of involved skin of atopic dermatitis patients. A non-invasive approach.

Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease mainly stemming from a genetic predisposition that leads to hypersensitivity to environmental factors and a common involvement of Staphylococcus aureus (SA) colonization. The aim of this work was to propose a new non-invasive approach to enumerate the genes coding for the toxins of SA in atopic skin samples. In parallel, the study aimed to evaluate the change in AD through 3 markers of the inflammatory response: IL-8, IL-1RA/IL-1alpha and IL-18. These methods were tested on 31 patients with AD, and finally on a group of 19 subjects for whom clinical improvement had been reported after various treatments. The study revealed the presence of a large number of genes encoding toxins in atopic samples, indicating a high rate of SA colonization, and also an increase in the level of all cytokine markers in atopic skin compared to the skin of healthy subjects. Finally, we found a positive correlation between increases in the SCORAD (Scoring Atopic Dermatitis Index) value after treatment and the corresponding evolution of the SA density. These methods provide a means to clinically evaluate the course of AD, and may help in the development of potential treatments.

Impact of infant pneumococcal vaccination on invasive pneumococcal diseases in France, 2001-2006.

Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV) has been recommended in France since 2003 for children under the age of two years who are at risk due to medical or living conditions. From 2006, the recommendation has been extended to all children under two years. The impact of PCV introduction on the incidence of pneumococcal meningitis and bacteraemia and on the serotype distribution in French children and other age-groups was assessed using laboratory surveillance data. The coverage with three doses of PCV was 44% in children aged 6-12 months in 2006. From 2001/2002 to 2006, the incidence of pneumococcal meningitis decreased from 8.0 to 6.0 cases per 100,000, and the incidence of pneumococcal bacteraemia decreased from 21.8 to 17.5 cases per 100,000 in children under the age of two years. For the vaccine strains, the incidence of pneumococcal meningitis and bacteraemia decreased from 20,4 to 6.0 cases per 100,000, while the incidence of pneumococcal meningitis and bacteraemia due to non-vaccine strains increased from 9.4 to 17.5 cases per 100,000 in this time period. The incidence in older children and adults did not decrease. Further expansion of PCV coverage is expected to increase the impact of the vaccination in both children and adults. However, the fact that cases caused by vaccine serotypes have been partially substituted by cases of non-vaccine serotypes is likely to reduce the overall benefit of PCV in France, should this early observation be confirmed in the future.

[Implementing a community surveillance network to monitor antimicrobial resistance: the Labville network]. / Mise en oeuvre d'un réseau de surveillance de la résistance bactérienne aux antibiotiques en ville: le réseau Labville.

BACKGROUND: In France, antimicrobial resistance monitoring is based on the contribution of many microbiological partners and networks, especially hospital laboratories. In order to complete this surveillance, the InVS implemented a network based on private-sector laboratories (PSL): the Labville network. METHOD: Stratified by French region, 69 PSL were randomly selected. The microbiological analysis results, including anonymized individual patient data, are translated into an appropriate data format within an automated reading process. This data is then sent to InVS through a secure Internet connection. RESULTS: The specifications of the automated system were defined according to a feasibility study conducted in 2003. The first stage of the project consisted in defining a global strategy for the reading of printed microbiological results. Then, the parameters were adapted for each PSL using a set of specific analysis over two to three weeks. After validation by InVS, the reading strategy was applied on to routinely printed results. The strategy was definitely validated after four month of a daily data transmission. The general approach needs to be adapted to each PSL and undergoes several adjustments. This long step of the project still requires microbiological expertise. CONCLUSION: The automated data extraction process used for Labville project is innovating. It is not affected by the compatibility and diversity of computing systems and reduces the biologist's workload. The Labville network is a challenging project motivating future development of other electronic surveillance networks.

Invasive amebiasis and ameboma formation presenting as a rectal mass: An uncommon case of malignant masquerade at a western medical center.

A 54-year-old man presented with rectal pain and bleeding secondary to ulcerated, necrotic rectal and cecal masses that resembled colorectal carcinoma upon colonoscopy. These masses were later determined to be benign amebomas caused by invasive Entamoeba histolytica, which regressed completely with medical therapy. In Western countries, the occurrence of invasive protozoan infection with formation of amebomas is very rare and can mistakenly masquerade as a neoplasm. Not surprisingly, there have been very few cases reported of this clinical entity within the United States. Moreover, we report a patient that had an extremely rare occurrence of two synchronous lesions, one involving the rectum and the other situated in the cecum. We review the current literature on the pathogenesis of invasive E. histolytica infection and ameboma formation, as well as management of this rare disease entity at a western medical center.

Validation of use of a traditional antimalarial remedy from French Guiana, Zanthoxylum rhoifolium Lam.

Zanthoxylum rhoifolium bark (Rutaceae) is a medicinal plant, traditionally used in French Guiana to treat and prevent malaria. Bioassay-guided extractions of Zanthoxylum rhoifolium bark have shown that antiplasmodial activity is concentrated in the alkaloid fraction. Further fractionation of this extract has yielded seven benzophenanthridine alkaloids, dihydroavicine 1, dihydronitidine 2, oxyavicine 3, oxynitidine 4, fagaridine 5, avicine 6 and nitidine 7. Antimalarial activity of the last five compounds has been evaluated, and nitidine was the most potent, displaying an IC(50)<0.27microM against Plasmodium falciparum. Investigation of the traditional remedy, a trunk bark decoction in water, has shown that fagaridine 5, avicine 6 and nitidine 7 are also present in the decoction, therefore justifying the traditional use of Zanthoxylumrhoifolium bark as antimalarial.

Impact of the pneumococcal conjugate vaccines on invasive pneumococcal disease in France, 2001-2012.

CONTEXT AND AIMS: Vaccination with the 7-valent pneumococcal conjugate vaccine (PCV7) was recommended in France in 2003 for children <2 years. The 13-valent conjugate vaccine (PCV13) replaced PCV7 in 2010. We assessed the impact of PCVs vaccination on the incidence of invasive pneumococcal diseases (IPD) in French children (0-15 years) and adults (>15 years). METHODS: IPD rates were calculated using cases reported from 2001 to 2012 to Epibac, a laboratory network. The distribution of serotypes was assessed from invasive isolates serotyped at the National reference Centre for Pneumococci. IPD incidence rates were compared between the pre-PCV7 (2001-2002), late PCV7 (2008-2009) and post PCV13 (2012) periods. RESULTS: The PCVs coverage increased from 56% in the 2004 birth-cohort to 94% in the 2008 and following birth-cohorts. Following PCV7 introduction, IPD incidence decreased by 19% between 2001-2002 and 2008-2009 in children <2 years, but increased in children aged 2-15 years and adults, despite a sharp decline in PCV7-IPD in all age-groups. After PCV13 introduction, IPD incidence decreased by 34% in children <5 years, by 50% in those aged 5-15 years and 15% in adults from 2008-2009 to 2012. The incidence of PCV13-Non PCV7-IPD decreased by 74% in children <5 years and by 60% in those aged 5-15 years. CONCLUSIONS: Vaccination with PCV13 was rapidly followed by a decrease in the incidence of all-type IPD in children, in relation with a sharp decrease in the incidence of PCV13-Non PCV7-IPD. Moreover, all-type IPD decreased after PCV13 introduction in older non-vaccinated age-groups, with a shift in the distribution of serotypes. Considering the whole 2001-2012 period, the vaccination with PCV7 and PCV13 resulted in a decline in the incidence of IPD in children up to the age of 5 but not in older children and adults.

Augmentation therapy for alpha(1)-antitrypsin deficiency.

alpha(1)-Antitrypsin (AAT) deficiency is a common but under-recognised condition. Since its first description by Laurell and Eriksson in 1963, significant advances have been made in understanding the genetics, physiology and pathophysiology of this condition. The intravenous administration of purified AAT to AAT-deficient individuals has been shown to confer biochemical efficacy by raising the serum AAT level above an epidemiologically established 'protective threshold' while preserving the biochemical properties and functional capacity of the protease inhibitor. Although the lack of a large randomised controlled trial to date has precluded the definitive demonstration of clinical efficacy of intravenous AAT augmentation therapy, substantial evidence supporting its use in AAT-deficient individuals with moderate airflow obstruction has accumulated. For example, both large observational studies comparing rates of forced expiratory volume decline among recipients of augmentation therapy versus non-recipients have shown slower rates of decline among augmentation therapy recipients, especially those with moderately severe airflow obstruction. Also, some evidence suggests that use of augmentation therapy confers an anti-inflammatory effect. For example, a web-based survey suggested that recipients of augmentation therapy experienced fewer respiratory infections than non-recipients. Despite its high cost, intravenous AAT augmentation therapy remains the only US FDA-approved treatment option for patients with AAT deficiency. Research into new and evolving treatments is currently underway.

Periareolar mediastinoscopy: a new technique.

Biopsy of anterior mediastinal or aortopulmonary nodes is usually accomplished through a left anterior mediastinostomy. Cosmetic concerns expressed by patients about scars in the neck or the upper chest led us to consider a new periareolar approach for mediastinoscopy. This technique has been used successfully in 10 patients.

[Development of resistance to beta-lactams and other antibiotics of pneumococci isolated from acute otitis media in France: statement of the National Reference Center 1995-1996]. / Evolution de la résistance aux bêtalactamines et aux autres antibiotiques des pneumocoques isolés d'otites moyennes aiguës en France: bilan du Centre national de référence 1995-1996.

POPULATION AND METHODS: During 1995 and 1996, 393 and 566 strains of Streptococcus pneumoniae, isolated from acute otitis media, were respectively sent to the National Reference Center for Pneumococci by its corresponding centers. RESULTS: The resistance rates for 1995 and 1996 were respectively: for penicillin: 65.4 and 70.3% (18.6 and 24.9% of intermediately resistant strains, 46.8 and 45.4% of fully resistant strains), for erythromycin: 57.5 and 68.5%, for tetracycline: 43.2 and 42.6%, for trimethoprim-sulfamethoxazole: 47.5 and 50.9%. Minimal inhibitory concentrations (MICs) of various betalactams were determined against a representative sample of strains (n = 99). CONCLUSION: Amoxicillin, cefpodoxime and cefuroxime MICs remained low against numerous penicillin resistant strains, indicating that these three oral antibiotics (in combination with clavulanate for amoxicillin) have a useful potential for the treatment of acute otitis media when risk factors for pneumococcal penicillin-resistant infections are detected.

Immediate postoperative parastomal end sigmoid hernia resulting in evisceration and strangulation.

Parastomal evisceration is a very rare complication occurring after stoma formation. We report the case of this complication which occurred within 3 days status post end sigmoid colostomy in a 69-year-old male who initially presented with perianal infection-severe necrotizing fasciitis. This case highlights the significance of the size of a stomatal aperture and should remind general surgeons of the one of dangerous complications indicated by a stomatal aperture that is just a centimeter larger than the accepted ideal size.