Human papillomavirus prevalence, persistence and cervical dysplasia in females with cystic fibrosis.

BACKGROUND: A higher risk of human papillomavirus (HPV)-related cervical intra-epithelial neoplasia (CIN) is suspected among females with cystic fibrosis (CF). METHODS: We conducted a single center prospective cohort study among females attending the Lyon adult CF center. We performed a cervical cytology (Hologic Thinprep®) and HPV testing with genotyping (Clinical Arrays Papillomavirus; Genomica, enabling 35 genotype detection, 20 of which are high-risk (HR-HPV)) at inclusion. We followed all females with positive HPV tests at 6, 12 and 24 months to evaluate HPV persistence, and performed a colposcopy in cases of abnormal cytology. RESULTS: We included eighty-five participants, 18 (21%) of whom were lung-transplanted. The mean age at inclusion was 31.9 (range 18-59) years. The prevalence of HPV (all types) was 31.8%. HR-HPV was found in 25.9% of the whole cohort, 44.4% of transplanted patients, and 20.1% of nontransplanted patients. Genotype-specific HR-HPV persistence at 12 months was 43.5% among transplanted and 34.6% among nontransplanted patients. Overall, 17.6% (15/85) of females had an abnormal cytology: 44.4% (8/18) among transplanted and 10.4% (7/67) among nontransplanted patients. CIN was identified in 12 (14.1%) patients (6 low-grade, 6 high-grade). High-grade CIN developed in 4 nontransplanted patients. CONCLUSION: Transplanted females had high HR-HPV, abnormal cervical cytology and CIN prevalence rates compared to large published cohorts in the general non-CF population. Although HR-HPV prevalence and persistence were globally not significantly different in nontransplanted females compared to the general population, we reported high frequencies of abnormal cytology and CIN. Cervical cancer screening and prevention should be promoted among females with CF.

[Place of internal medicine specialists in inpatient unprogrammed care of adult patients in France: A survey of in training and senior internal medicine specialists]. / Place des internistes dans la prise en charge hospitalière de la médecine adulte non programmée : enquête auprès des internistes en formation et en exercice.

INTRODUCTION: French internal medicine specialists are trained in clinical immunology and rare diseases as well as frequent ones. The latest activity is rarely highlighted by practitioners themselves and their representative authorities. Frequent diseases care in French hospitals are also the tasks of physicians without internal medicine specialty, mostly trained in general medicine, who practice in departments carrying various names. METHODS: We conducted a survey to estimate the part of frequent diseases' care and unplanned hospital medicine in the practice of specialists and residents in internal medicine in France, and its designation, through two surveys released by the "Collège National Professionnel de Médecine Interne" (for the internal medicine specialists), and the "Amicale des Jeunes Internists" (for the internal medicine residents). RESULTS: A total of 180 and 247 responses were obtained among the residents and the specialists, respectively, representing 31.3% and 24.8% of the internal medicine specialist's workforce. The most suitable qualifier for frequent diseases' care and unplanned hospital medicine, primarily post-emergency, was "general hospital medicine" for 48.9% of the residents and "general internal medicine" for 35.6% of the specialists. Unplanned hospital medicine was considered to represent a large part of the internal medicine activity by 66.7% and 64.7% of residents and specialists, respectively. A 50% and more hourly part of the activity devoted to it was reported by 71.4% of the residents and 76.1% of the specialists. General hospital medicine was reported to be distinct from internal medicine-clinical immunology by 46.1% of the residents and 47.4% of the specialists. CONCLUSION: French internists devote a large part of their activities to frequent diseases' care and unscheduled medicine, the name of which was not consensual. However, their work could not be summarized to it, often involving a specific activity named internal medicine - clinical immunology.

[Human papillomavirus and systemic lupus erythematosus]. / Papillomavirus humain et lupus érythémateux systémique.

Infection with human papillomavirus (HPV) is one of the most widespread sexually transmitted diseases and the main risk factor for cervical cancer. Underlying conditions, like immunosuppression, favour the persistence and the progression of cervical lesions to an aggressive form. Patients with autoimmune diseases, and particularly systemic lupus erythematosus (SLE), may be prone to HPV infection and cervical dysplasia. However, the risk factors for developing persistent HPV-related infection, dysplasia and cancer are not identified for patients with SLE. The existence of an increased risk of cervical cancer compared to the general population remains debated. Thus, HPV vaccine is recommended for SLE patients as well as for the general population. Vaccine coverage of SLE patients is not known in France. Adolescents with chronic health condition seem to be insufficiently vaccinated regarding their vulnerability to infectious diseases. Strategies are required to decrease HPV vaccination barriers.

Twice- or Once-Daily Dosing of Direct Oral Anticoagulants, a systematic review and meta-analysis.

AIM: The direct oral anticoagulants (DOAC) have similar half-lives, but the dosing regimen varies between once daily (QD) or twice daily (BID). For some prescribers, the QD regimen improves compliance. Others prefer BID regimens to promote better stability of plasma concentrations, particularly in the event of missed doses. Limited level of evidence provides guidance about the best treatment strategy. The purpose of this study was to compare the treatment effect of QD vs. BID administration of DOACs in major orthopedic surgery (MOS), non-valvular atrial fibrillation (NVAF), venous thromboembolism (VTE), and acute coronary syndrome (ACS). METHODS: We conducted a systematic review up to April 2020. We included phase II clinical trials comparing DOAC QD vs BID with same daily dose. We extracted data for the occurrence of major thrombosis (proximal deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke) and major hemorrhage (ISTH criteria and recommendations of the European Medicines Agency for surgical patients). Relative risks (RR) were combined using a fixed and random effects weighted meta-analysis. RESULTS: Twelve randomized, controlled, phase II trials were included (10,716 patients), representing 24 dosing regimen comparisons of apixaban, darexaban, edoxaban, rivaroxaban, letaxaban, and dabigatran. There was no difference for major thrombotic event (RRBID/QD = 1.06, 95%IC 0.86-1.30) nor for major bleeding (RRBID/QD = 1.02, 95%IC 0.84-1.23) between the BID vs QD regimens, without heterogeneity (I2 = 0%). CONCLUSION: Our study does not support a global difference in term of efficacy and safety of the BID and QD regimens of DOAC in MOS, NVAF, VTE and ACS.

Sarcoidosis diagnosed in the elderly: a case-control study.

BACKGROUND: Studies on sarcoidosis in elderly patients are scarce and none have specifically evaluated patients aged ≥75 at onset. AIM: We aimed to analyse the characteristics of patients with sarcoidosis diagnosed after 75 and to compare them with those of younger patients. DESIGN: Multicenter case-control study comparing elderly-onset sarcoidosis (EOS) with young-onset sarcoidosis (YOS) seen at Lyon University Hospitals between 2006 and 2018. METHODS: Using our institutional database, we included 34 patients in the EOS group and compared them with 102 controls from the YOS group in a 1:3 ratio. Demographic characteristics, medical history, clinical presentation, laboratory and imaging findings, sites of biopsies, histological analyses, treatments and outcomes were recorded using a comprehensive questionnaire. RESULTS: There were more Caucasians in the EOS group (94.1% vs. 59.8%; P < 0.001), who had significantly more comorbidities (mean, 3.1 ± 2 vs. 1.1 ± 1.6; P < 0.001). In the EOS group, there was less pulmonary involvement (26.5% vs. 49%; P = 0.022), less lymphadenopathy (2.9% vs. 16.7%; P = 0.041), no erythema nodosum (0% vs. 12.8%; P = 0.029) and no arthralgia (0% vs. 25.5%; P = 0.001). Conversely, uveitis was more common in the EOS group (55.9% vs. 20.6%; P < 0.001). Pathological confirmation was obtained significantly less frequently in the EOS group (67.7% vs. 85.3%; P = 0.023). Corticosteroid-related side effects were significantly more common in the EOS group (100% vs. 75.9%; P = 0.030). CONCLUSION: Epidemiology and clinical presentation of EOS differs from YOS, including more comorbidities and more uveitis. Elderly patients are more prone to corticosteroid side effects.

[Tryptase: A practical guide for the physician]. / Dosage de la tryptase : un guide d'utilisation pour le clinicien.

Tryptase is the most abundant endopeptidase released by mast cells degranulation, involved in many pro and anti-inflammatory processes. Normal serum tryptase range is 0-11.4 µg/L. Tryptase is a useful diagnostic tool for anaphylaxis, systemic mastocytosis (SM) and mast cell activation syndrome (MCAS), where specific threshold values must be used. SM diagnosis criteria include evidence of dense mast cell infiltrate either in the bone marrow or the affected organ (such as skin), presence of KIT D816V mutation and elevated serum tryptase level (>20 µg/L). In SM, tryptase level is correlated with the burden of mast cells in bone marrow. MCAS should be considered in case of severe and recurrent typical clinical signs of systemic mast cell activation involving at least two organs, associated with an increase in serum tryptase level of 20% + 2 µg/L from the individual's baseline. Anaphylaxis is the most severe among hypersensitivity reactions. A clonal mast cell disorder is a central question in anaphylaxis and appropriate explorations should be conducted in these patients. Triggers for anaphylactic reactions vary significantly in the general population and in patients with MS or MCAS. Finally, physicians must be aware of the many pathological and physiological situations that affect tryptase levels.

[Aceruloplasminemia, a rare condition not to be overlooked]. / L'acéruléoplasminémie héréditaire, une pathologie à ne pas méconnaître.

Aceruloplasminemia is a rare iron-overload disease that should be better known by physicians. It is an autosomal recessive disorder due to mutations in ceruloplasmin gene causing systemic iron overload, including cerebral and liver parenchyma. The impairment of ferroxidase ceruloplasmin activity leads to intracellular iron retention leading aceruloplasminemia symptoms. Neurologic manifestations include cognitive impairment, ataxia, extrapyramidal syndrome, abnormal movements, and psychiatric-like syndromes. Physicians should search for aceruloplasminemia in several situations with high ferritin levels: microcytic anaemia, diabetes mellitus, neurological and psychiatric disorders. Diagnosis approach is based on the study of transferrin saturation and hepatic iron content evaluated by magnetic resonance imaging of the liver. Ceruloplasmin dosage is required in case of low transferrin saturation and high hepatic iron content and genetic testing is mandatory in case of serum ceruloplasmin defect. Neurological manifestations occur in the sixties decade and leads to disability. Iron chelators are widely used. Despite their efficacy on systemic and cerebral iron overload, iron chelators tolerance is poor. Early initiation of iron chelation therapy might prevent or slowdown neurodegeneration, highlighting the need for an early diagnosis but their clinical efficacy remains uncertain.

[Functional immunoassays in the setting of infectious risk and immunosuppressive therapy of non-HIV immunocompromised patients]. / Place des tests immunitaires fonctionnels dans la prise en charge du risque infectieux et de la gestion des thérapies immunosuppressives chez les patients immunodéprimés non-VIH.

The holistic approach of the human immune system is based on the study of its components collectively driving a functional response to an immunogenic stimulus. To appreciate a specific immune dysfunction, a condition is mimicked ex vivo and the immune response induced is assessed. The application field of such assays are broad and expanding, from the diagnosis of primary and secondary immunodeficiencies, immunotherapy for cancer to the management of patients at-risk for infections and vaccination. These assays are immune monitoring tools that may contribute to a personalised and precision medicine. The purpose of this review is to describe immune functional assays available in the setting of non-HIV acquired immune deficiency. First, we will address the use of theses assays in the diagnosis of opportunistic infections such as viral reactivation. Secondly, we will report the usefulness of these assays to assess vaccine efficacy and to manage immunosuppressive therapies.

[Terminology of patient engagement for French healthcare organizations]. / Approche terminologique de l'engagement des patients : point de vue d'un établissement de santé français.

BACKGROUND: The establishment of a common pragmatic terminology represents the first step in structuring patient engagement initiatives in healthcare facilities. However, none is currently available in French. As part of the deployment of patient engagement within a French University Hospital Center, we propose a terminology of patient engagement. METHODS: We conducted a scoping review of the international literature that aimed at identifying the main conceptual and terminological frameworks for the engagement of patients, users and citizens in the healthcare system until 2019 in the PubMed and Cairn.info databases for English and French language articles. Additionally, we identified concepts and practices in the leading organizations of countries where this approach was implemented (United States, Canada and especially the province of Quebec, United Kingdom) and completed this approach by close exchanges and reflections with the team that developed the Montreal model. RESULTS: In total, 75 references and Internet resources were consulted. Patient, interaction, patient experience, experiential knowledge, patient engagement, patient partner and its variations as a resource patient, peer-supporter, trainer, researcher and coach have been defined. CONCLUSION: This terminology of patient engagement proposes an initial stabilization of the vocabulary, using a pragmatic approach. This contribution is a first step aiming at promoting the development of a new model of care and more broadly of healthcare system management, involving scientific and experiential knowledge.

Acute renal and splenic infarctions: a review.

BACKGROUND: Renal and splenic infarctions are close entities, with few data concerning their clinical, biological and radiological features. AIM: The aim of this study was to compare the clinical presentations, etiologies and outcomes of acute renal infarctions (RI) and splenic infarctions (SI). DESIGN: A retrospective multicentric cohort study included patients of the 6 university hospitals in Lyon with RI, SI, or associated RI-SI infarctions was conducted. METHODS: All consecutive cases diagnosed by CT imaging, between January 2013 and October 2016, were included. The exclusion criteria were causes of infarction that did not require additional investigations. RESULTS: A total of 161 patients were selected for analysis: 34 patients with RI, 104 patients with SI and 23 patients with both RI-SI. Mean ± SD age of patients was 63.2 ± 16.6 years; 59.6% were male. Only 5/161 (3.1%) were healthy prior to the event. The main symptoms were diffuse abdominal pain (26.4%), followed by nausea/vomiting (18.3%) and fever (16.4%).The causes of RI or SI varied significantly within the three groups. Hypercoagulable state was associated with SI, and embolic disease and arterial injury were associated with RI. Extensive (i.e.>2/3 of organ volume) (OR 6.22, 95%CI 2.0119.22) and bilateral infarctions (OR 15.05, 95%CI 1.79-126.78) were significantly associated with hemodynamic shocks. The survival at 1 month follow-up did not significantly differ between the three groups. CONCLUSION: Acute RI and SI are heterogenous entities in regards to their clinical presentation, etiology, associated venous or arterial thrombosis, but prognoses were not different at short term follow-up.

Improvement in contraceptive coverage and gynecological care of adult women with cystic fibrosis following the implementation of an on-site gynecological consultation.

OBJECTIVE: Our study aimed to evaluate the impact of the introduction of a new gynecologic referral service in our adult Cystic Fibrosis (CF) center on contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage. STUDY DESIGN: We implemented an on-site gynecological consultation in our adult CF center in 2015. We compared the results of two surveys conducted successively in 2014 and in 2017 in a cohort of women with CF attending the Lyon CF center. Women completed the same self-report written questionnaire as in 2014. Main outcome measures were the comparisons of contraceptive coverage, gynecological follow-up regularity, and cervical cancer screening coverage between 2014 and 2017. RESULTS: All the 136 women (100%) who attended the clinic in 2017 participated. Contraceptive prevalence rate increased from 69%(CI95%:60.3-78.1) to 86%(CI95%:79.6-92.9) between 2014 and 2017 (p = 0.005). Among transplanted patients, the contraceptive prevalence rate was 92.3%(CI95%:82.0-100) in 2017. Long acting reversible contraceptive use markedly increased from 10% to 21.6% (p = 0.005). The proportion of women that reported an access to gynecological care increased between 2014 and 2017 (74%(CI95%:66.3-82.0) vs 91%(CI95%:86.9-95.4), p < 0.005) and reached 100% among transplanted patients. Cervical cancer screening improved (55%(CI95%:51.2-68.8) vs 85%(CI95%:78.6-90.6) women ever screened) (p < 0.0005) and reached 100% among transplanted patients. CONCLUSIONS: We observed an improvement in contraceptive coverage and gynecological care of adult women with CF following the implementation of a dedicated gynecological consultation in the CF center. IMPLICATIONS: Service linkages and formal links between CF centers and gynecologists can facilitate access to disease-specific contraceptive counseling, adequate gynecological management and cervical cancer screening.

[Quality criteria for the transition to adult care in French CF centers - results from the SAFETIM APP study?] / Critères de qualité pour la transition dans la mucoviscidose en France (suivi des adolescents, des familles et des équipes, pour une transition idéale en mucoviscidose ­ analyse des pratiques professionnelles).

INTRODUCTION: SAFETIM-APP compiled an inventory of professional practice in the 45 French cystic fibrosis reference centres (CFRC), between February 2015 and December 2016, related to the transition of adolescents with cystic fibrosis to adult centres. METHOD: This multicentre cross-sectional study addressed the modalities of the transition in CFRCs and proposed a list of items that could be used to establish quality criteria. Quantitative analysis of the criteria and a qualitative analysis of the transition procedure were carried out. RESULTS: A total of 77% of the CFRCs that were contacted took part. Transition lasted 3 to 5 years and began at around 15 years of age. Nine criteria were described as fundamental, including: collaboration between teams, taking adolescence into account, having a time for adolescents to speak with the physician alone, defining a program including therapeutic education, involving the family, accompanying the parents. Seven additional criteria were noted to be important, including: re-announcing the diagnosis, identifying a common thread (caregiver) accompanying the family, scheduling adult follow-up from paediatrics onwards, visiting the adult department, organizing a formal departure/reception time, initiating the process early enough, identifying indicators to evaluate practices. CONCLUSION: The transition processes in place in CFRCs can be improved by implementing the use of these quality criteria systematically.

[Gynecological management and follow-up in women with cystic fibrosis]. / Suivi et prise en charge gynécologique chez les femmes atteintes de mucoviscidose.

INTRODUCTION: Most women with cystic fibrosis reach adulthood and should have appropriate gynecological follow-up and contraception. BACKGROUND: There is no specific contra-indication to any contraception due to cystic fibrosis itself. Combined estrogen-progesterone contraception can be used in most cases (including transplanted women). In case of transplantation, intra-uterine devices should be used carefully (risk of pelvic inflammatory disease, potential risk of contraceptive failure with copper intra-uterine devices). Hormonal contraceptives may not be effective in women taking corrective treatments aiming to correct the maturation defect of the chloride channel. Screening for cervical cancer is recommended with a pap smear every three years for women aged 25-65, but yearly and starting at a younger age among transplanted women who are at higher risk for cervical dysplasia. Human Papillomavirus vaccination should be offered to all young women. OUTLOOK: Women with cystic fibrosis and health care providers should be better informed on screening and on sexual and reproductive health to avoid unplanned pregnancies, to take into account drug interactions and to prevent cervical disease. CONCLUSION: Regular and specific gynecological management is mandatory in cases of cystic fibrosis.

Coxiella burnetii infection (Q fever) mimicking systemic lupus erythematosus: two cases.

Q fever has extremely polymorphic features, and has been reported to be associated with positivity of several autoimmune antibodies. We report two cases of atypical Q fever with a clinical presentation highly suggestive of an inflammatory systemic disease with positivity of autoimmune antibodies, mimicking systemic lupus erythematosus.

A multicentre, prospective, non-randomized, sequential, open-label trial to demonstrate the bioequivalence between intravenous immunoglobulin new generation (IGNG) and standard IV immunoglobulin (IVIG) in adult patients with primary immunodeficiency (PID).

OBJECTIVES: To demonstrate the bioequivalence between 2 intravenous immunoglobulin (IVIG) preparations, TEGELINE® and ClairYg®, a ready-to-use 5% IVIG, in primary immunodeficiency (PID). Secondary objectives were to assess the efficacy, safety and pharmacokinetics of ClairYg®. METHODS: Twenty-two adult PID patients receiving stable doses of TEGELINE® (5% lyophilized IVIG) were switched to ClairYg® for 6 months. ClairYg® was administered under the same conditions as TEGELINE®, either every 3 or 4 weeks. The primary endpoint was mean average total IgG trough level at steady state with ClairYg® versus TEGELINE®. Clinical efficacy was also assessed in terms of infections and associated events. RESULTS: Bioequivalence was established with a mean average total IgG trough level at steady state being 8.05g/L with TEGELINE® and 9.17g/L with ClairYg® (i.e. geometric mean for the difference between ClairYg® and TEGELINE® was 1.136; [90% CI: 1.092-1.181] P<0.001), within the pre-specified margin to establish bioequivalence (0.80-1.25). Total IgG trough levels remained clinically adequate (>4-6g/L) throughout the study. No patient was hospitalized for infection or had serious bacterial infections while receiving ClairYg®. The median annualized infections rate per patient was similar for both products: 4.35 [0; 21.8] for TEGELINE® and 4.30 [0; 15.1] for ClairYg®. Infections were less common with higher IgG trough levels (>8.16g/L). ClairYg® showed good safety, in particular good hepatic and renal tolerance, and did not induce hemolysis. ClairYg® pharmacokinetics profile was comparable to that of TEGELINE®. CONCLUSION: ClairYg® is safe and effective in the treatment of adult PID.