Bilateral Septic Neonatal Orchiepididymitis - Case Report.

Neonatal epididymo-orchitis is a rare condition, causing testicular pain in neonatal boys. It represents epididymo-testicular inflammation which commonly coexists with urinary tract infections and malformations. The idiopathic type is extremely rare. We present a case of a seven-day old male neonate with advanced septic form of idiopathic orchiepididymitis and no associated urinary tract anomalies. The boy was hospitalized with signs of sepsis, anterior abdominal wall phlegmona and bilateral acute scrotum. Colour Doppler echosonography indicated epididymo-testicular inflammation with increased vascular flow. The patient underwent surgical exploration of both scrota in order to evacuate purulent content and fibrin. Cultures of Enterobacter spp were detected in hemiscrotal pus. Prompt administration of antibiotics was done. The postoperative course was uneventful. We suggest that every male baby must be very meticulously examined by a neonatologist in the early postnatal period, in order to prevent infertility.

Blunt Trauma in Paediatric Patients - Experience from a Small Centre.

OBJECTIVE: Despite great prevention efforts, blunt abdominal trauma still remains a leading cause of injury, especially in the paediatric population. Abdominal trauma is the main culprit of serious children's injury and the most common area of initially missed diagnosis with a fatal outcome. AIM: The purpose of this study was to determine the incidence, aetiology, grades of abdominal organ injuries, diagnosis, management and outcome of blunt abdominal trauma in a paediatric population. METHOD: This is a retrospective study of 31 patients with isolated parenchymatous abdominal organs, treated in a single centre. Stable patients with no signs of peritonitis and insignificant changes in laboratory findings were managed conservatively. Unstable patients received surgery. RESULTS: The leading cause of injuries were traffic accidents (64.5%), followed by fall from a height (22.5%), bicycle handlebar injuries (6.45%), contact sport and child abuse (3.22% each). The majority of injured children (90.32%) were managed conservatively. Only three patients (9.68%) were operated on due to complete avulsion and organ smash, or devascularization of the injured organs. Diagnostic computed tomography (CT) scan examination was performed on 93.5% of patients. Few patients had grade I and grade V injuries, while the largest proportion of patients had grade III and IV injuries. The most frequently injured organs were the spleen and kidney. There was no mortality. CONCLUSION: The results emphasize that conservative treatment was appropriate for all stable patients with blunt abdominal trauma regardless of organ injury grade. The success of non-operative management depends upon proper patient selection. The choice of non-operative treatment should be based predominantly on physiological response, rather than grade injury on CT scan.

[Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC]. / Autogreffe des cellules souches hématopoïétiques dans les maladies auto-immunes : recommandations de la SFGM-TC.

Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients.

French protocol for the diagnosis and management of hematopoietic stem cell transplantation in autoimmune diseases.

Hematopoietic stem cell transplantation (HSCT) for severe ADs was developed over the past 25years and is now validated by national and international medical societies for severe early systemic sclerosis (SSc) and relapsing-remitting multiple sclerosis (MS) and available as part of routine care in accredited center. HSCT is also recommended, with varying levels of evidence, as an alternative treatment for several ADs, when refractory to conventional therapy, including specific cases of connective tissue diseases or vasculitis, inflammatory neurological diseases, and more rarely severe refractory Crohn's disease. The aim of this document was to provide guidelines for the current indications, procedures and follow-up of HSCT in ADs. Patient safety considerations are central to guidance on patient selection and conditioning, always validated at the national MATHEC multidisciplinary team meeting (MDTM) based on recent (less than 3months) thorough patient evaluation. HSCT procedural aspects and follow-up are then carried out within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and SFGM-TC accredited centres in close collaboration with the ADs specialist. These French recommendations were performed according to HAS/FAI2R standard operating procedures and coordinated by the Île-de-France MATHEC Reference Centre for Rare Systemic Autoimmune Diseases (CRMR MATHEC) within the Filière FAI2R and in association with the Filière MaRIH. The task force consisted of 3 patients and 64 clinical experts from various specialties and French centres. These data-derived and consensus-derived recommendations will help clinicians to propose HSCT for their severe ADs patients in an evidence-based way. These recommendations also give directions for future clinical research in this area. These recommendations will be updated according to newly emerging data. Of note, other cell therapies that have not yet been approved for clinical practice or are the subject of ongoing clinical research will not be addressed in this document.

Syndromic association of pyloric atresia and epidermolysis bullosa (Carmi syndrome)--a case report.

Epidermolysis bullosa (EB) is an inherited, autosomal recessive, bullous disease, characterized by blisters followed with skin and mucosal erosions. We present a case of a male infant with pyloric atresia associated with junctional EB (Carmi syndrome). The patient underwent urgent laparotomy after prompt stabilization. Postoperative course was uneventful. Nine months later the patient died in the paediatric intensive care unit from respiratory distress syndrome. Prognosis is usually very poor. Death usually occurs during the first year of life, as a result of septic complications.

Long-term use of tinzaparin for the treatment of cancer-associated thrombosis in clinical practice: Insights from the prospective TROPIQUE study.

BACKGROUND: Real word data on the efficacy and safety of long-term use of tinzaparin for the treatment of cancer-associated thrombosis (CAT) are scarce. METHODS: We performed a post-hoc analysis of all cancer patients included in the prospective multicenter observational TROPIQUE study who received long-term treatment with tinzaparin for a first venous thromboembolism (VTE) event. We evaluated the patterns of anticoagulant prescription, the adherence to clinical practice guidelines (CPGs) for the treatment of CAT, and the clinical outcomes within a 6-month follow-up. RESULTS: In total, 301 patients were included in this post-hoc analysis. At study entry, their mean age was 64.6±11.9years and 143 (47.5%) patients were men. The most frequent cancer type was gastrointestinal (23.9%), followed by breast (17.9%) and lung (15.3%) cancer. At time of VTE diagnosis, 164 (57.8%) patients had metastatic disease and 245 (81.42%) were receiving chemotherapy. Based on the aggregation of all study pre-defined criteria, tinzaparin prescription was fully compliant with CPGs in 219 (72.8%) patients. The mean effective treatment duration with tinzaparin was 6.07±0.17months. At 6-month follow-up, the cumulative incidence of recurrent VTE was 5.4% (95% CI: 3.2-9.2%) and the cumulative incidence of major bleeding was 5.8% (95% CI: 3.6-9.6%). Clinical outcomes tended to differ across different types of cancer. Death from any cause occurred in 102 (33.9%) patients, mainly related to cancer progression. CONCLUSIONS: This post-hoc analysis of TROPIQUE confirms the favorable benefit-risk ratio of tinzaparin for the long-term treatment of CAT.

Patient education program at the forefront of cancer-associated thrombosis care.

INTRODUCTION: Treatment of cancer-associated thrombosis (CAT) requires specific approaches, although it is well codified in most cases. Current national and international (International Initiative on Cancer and Thrombosis, ITAC) Clinical Practice Guidelines (CPG) recommend the use of low-molecular-weight heparin (LMWH) over 6 months as first treatment option, and anticoagulation should be maintained thereafter as long as cancer is active. Since compliance improves when patients understand their disease and related treatments, we created a dedicated patient education program (PEP) for CAT, aiming to improve quality of care. METHODS: Retrospective analysis of all patients who voluntarily joined the PEP for CAT from 2014 to 2020. RESULTS: In total, 182 cancer patients (median age, 64.9 years) were included, 53.3% with metastatic disease. A total of 528 PEP sessions (median, 3 per patient) were delivered. After PEP completion, the rate of self-injections or those performed at home by a relative had increased from 49.1% to 59.8% (P=0.05). Quality of life had improved significantly (P=0.025) and 90.0% of patients reported adhering to anticoagulant therapy. CONCLUSION: Implementation of a structured and personalized PEP for CAT is feasible, allowing to improve cancer patient empowerment, adherence to CAT treatment and quality of life. The Groupe francophone et cancer (GFTC) members aim at facilitating access to CAT-PEP for both patients and caregivers and use of the multi-language ITAC-CPG mobile app (free access: www.itaccme.com) to improve the care and quality of life of patients with CAT.

Drug-drug interaction (DDI) with direct oral anticoagulant (DOAC) in patients with cancer.

Cancer-associated thrombosis (CAT) is the second leading cause of death in cancer patients after tumor progression. The treatment of CAT is challenging because of a high risk of VTE recurrence, a high risk of bleeding, common presence of comorbidities, poly-medication, and potential drug-drug interactions (DDI). Since 2018, direct oral anticoagulants (DOACs) represent a promising therapeutic alternative and have been recently included into the 2019 update of the International Initiative on Thrombosis and Cancer (ITAC-CME) clinical practice guidelines for management of CAT. However, pharmacokinetic studies suggest that concomitant treatment with P-gp or CYP3A4 inhibitors will result in an increased exposure to rivaroxaban and apixaban, but the clinical relevance of these studies is unknown. In addition, there is an important inter-individual variability in drug absorption, distribution, metabolism and elimination, even more in cancer patients. Overall, the risk of pharmacokinetic DDI should be estimated based on several individual (patient age, renal and liver function, number of comedications) and diseases-related factors, including inflammation, sarcopenia, and low body weight. In this context, DDI with clinical implications could be expected with anti-neoplastic agents or supportive care treatments, especially with drugs known to be moderate or strong inhibitors/inducers of CYP3A4 and P-gp. Consequently, in the presence of potential DDIs through CYP3A4, and/or P-gp, LMWHs remain the first-line anticoagulant of choice for the long-term treatment of CAT. Multidisciplinary consultation meetings and therapeutic patient education should be emphasized in the complex management of CAT.

Management of cancer-related thrombosis in the era of direct oral anticoagulants: A comprehensive review of the 2019 ITAC-CME clinical practice guidelines. On behalf of the Groupe Francophone Thrombose et Cancer (GFTC).

Venous thromboembolism (VTE) is a common disease complication in cancer patients and the second cause of death after cancer progression. VTE management and prophylaxis are critical in cancer patients, but effective therapy can be challenging because these patients are at higher risk of VTE recurrence and bleeding under anticoagulant treatment. Numerous published studies report inconsistent implementation of existing evidence-based clinical practice guidelines (CPG), including underutilization of thromboprophylaxis, and wide variability in clinical practice patterns across different countries and various practitioners. This review aims to summarize the 2019 ITAC-CME evidence-based CPGs for treatment and prophylaxis of cancer-related VTE, which include recommendations on the use of direct oral anticoagulants specifically in cancer patients. The guidelines underscore the gravity of developing VTE in cancer and recommend the best approaches for treating and preventing cancer-associated VTE, while minimizing unnecessary or over-treatment. Greater adherence to the 2019 ITAC guidelines could substantially decrease the burden of VTE and improve survival of cancer patients.

Long-term follow-up results after autologous haematopoietic stem cell transplantation for severe systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a generalised autoimmune disease, causing morbidity and a reduced life expectancy, especially in patients with rapidly progressive diffuse cutaneous SSc. As no proven treatment exists, autologous haematopoietic stem cell transplantation (HSCT) is employed as a new therapeutic strategy in patients with a poor prognosis. This study reports the effects on survival, skin and major organ function of HSCT in patients with severe diffuse cutaneous SSc. PATIENTS AND METHODS: A total of 26 patients were evaluated. Peripheral blood stem cells were collected using cyclophosphamide (4 g/m2) and rHu G-CSF (5 to 10 microg/kg/day) and were reinfused after positive CD34+ selection. For conditioning, cyclophosphamide 200 mg/kg was used. RESULTS: After a median follow-up of 5.3 (1-7.5) years, 81% (n = 21/26) of the patients demonstrated a clinically beneficial response. The Kaplan-Meier estimated survival at 5 years was 96.2% (95% CI 89-100%) and at 7 years 84.8% (95% CI 70.2-100%) and event-free survival, defined as survival without mortality, relapse or progression of SSc, resulting in major organ dysfunction was 64.3% (95% CI 47.9-86%) at 5 years and 57.1% (95% CI 39.3-83%) at 7 years. CONCLUSION: This study confirms that autologous HSCT in selected patients with severe diffuse cutaneous SSc results in sustained improvement of skin thickening and stabilisation of organ function up to 7 years after transplantation.

Anti-tumor effect of Coriolus versicolor methanol extract against mouse B16 melanoma cells: in vitro and in vivo study.

Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo. In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.

Cardiopulmonary assessment of patients with systemic sclerosis for hematopoietic stem cell transplantation: recommendations from the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party and collaborating partners.

Systemic sclerosis (SSc) is a rare disabling autoimmune disease with a similar mortality to many cancers. Two randomized controlled trials of autologous hematopoietic stem cell transplantation (AHSCT) for SSc have shown significant improvement in organ function, quality of life and long-term survival compared to standard therapy. However, transplant-related mortality (TRM) ranged from 3-10% in patients undergoing HSCT. In SSc, the main cause of non-transplant and TRM is cardiac related. We therefore updated the previously published guidelines for cardiac evaluation, which should be performed in dedicated centers with expertize in HSCT for SSc. The current recommendations are based on pre-transplant cardiopulmonary evaluations combining pulmonary function tests, echocardiography, cardiac magnetic resonance imaging and invasive hemodynamic testing, initiated at Northwestern University (Chicago) and subsequently discussed and endorsed within the EBMT ADWP in 2016.

Advanced Form of Hepatopulmonary Hydatidosis in a Child: Case Report

ABSTRACT Hepatopulmonary hydatidosis (HPH) is a very rare condition in children with a prevalence of 11%. An 8-year-old girl with advanced HPH was successfully treated in our institution without complications. The coexistence of large numbers of high hydatid cyst makes this case very unusual and interesting.

[A tamponade complicating an acute eosinophilic pericarditis due to a myeloproliferative/myelodysplastic syndrome]. / Une tamponnade compliquant une péricardite à éosinophiles au cours d'un syndrome myéloprolifératif/myélodysplasique.

Cardiac involvement in eosinophilia is potentially fatal and requires early diagnosis and prompt treatment. We report here the case of a 71-year-old female patient with eosinophilia>10,000/mm(3) for 2 months due to a myeloproliferative/myelodysplastic syndrome, with a rapidly progressive exertional dyspnea explained by an important circumferential eosinophilic pericarditis. Due to a rapid evolution to a tamponade, an emergent surgical drainage was performed. Subsequent medical treatment combined high-dose corticosteroids (1mg/kg/day) with hydroxyurea and imatinib. The outcome was favourable with regression of the effusion, of the volume overload symptoms and decrease in eosinophilia.

Validation of French version of the Scleroderma Health Assessment Questionnaire (SSc HAQ).

The modified Scleroderma Health Assessment Questionnaire (SSc HAQ) is a functional score to assess systemic sclerosis (SSc) comprising the HAQ disease index (HAQ-DI) plus five specific visual analogue scales (VAS). Since it was validated in English-speaking patients only, its general use in any other language necessitates prior cross-cultural adaptation and validation. We designed this study to assess its value in French-speaking patients and to validate the French version according to international recommendations. We elaborated a French version using the "forward-backward" method. We then validated its psychometric properties with 100 consecutive SSc French-speaking patients who had undergone simultaneous clinical and paraclinical examination. In addition, we calculated the SSc HAQ score, a new outcome measure, which is obtained by pooling the eight domains from the HAQ-DI with the five organ VAS. Our study confirmed the psychometric properties of the SSc HAQ in non-English-speaking patients with (a) structural validity: the major component analysis, performed on the HAQ-DI and the five VAS, yielding a two-factor structure; (b) convergent validity: with high correlation coefficients between the SSc HAQ score and the physical component score of the SF-36 (r=-0.74, p<0.0001); (c) discriminant validity: the SSc HAQ score was better in patients with limited than with diffuse SSc (0.5+/-0.5 vs 1.1+/-0.7, respectively, p<0.0001) in relation to the number of clinical involvements; (d) reproducibility was high using the test-retest procedure (r=0.98). This study showed the value of the SSc HAQ, which is a simple, discriminant, reproducible self-administered questionnaire to evaluate French-speaking SSc patients. In addition, we suggest the use of a new outcome measure, the SSc HAQ score, to assess this systemic disease more accurately.

[Cardiopulmonary function before and after cyclophosphamide treatment in severe systemic sclerosis: comparison of monthly intravenous bolus and autologous haematopoietic stem cell transplantation]. / Etude de la fonction cardiopulmonaire avant et après traitement par cyclophosphamide dans la sclérodermie systémique sévère: comparaison de deux modes d'administration (Intensification thérapeutique suivie d'autogreffe de cellules souches hématopoïétiques périphériques ou bolus mensuels intraveineux).

PURPOSE: Cyclophosphamide in monthly intravenous bolus is used to treat severe forms of systemic sclerosis with pulmonary involvement. Since 1996, cyclophosphamide therapeutic intensification with autologous haematopoietic stem cells transplantation allowed significant improvement in skin and functional scores in severe systemic sclerosis. Cyclophosphamide potential cardiotoxicity in this setting has been questioned. METHODS: To analyse cyclophosphamide potential cardiopulmonary toxicity (as graded with WHO classification), we retrospectively studied all severe systemic sclerosis patients treated with cyclophosphamide either during autologous haematopoietic stem cells transplantation procedure (group A) or intravenous cyclophosphamide (group B) recruited in 7 French centers volunteers for the study. Parameters to evaluate heart and lung functions at inclusion, then at last follow-up between 6 and 12 months after start of treatment, were compared using the Mann-Whitney test. RESULTS: (Mean+/-standard deviation): Groups A (N=14) and B (N=13) were similar at the beginning of the study in terms of skin, renal, heart and lung involvement. Cyclophosphamide total dose (/m(2)) received in group A was superior (P=0.02) to the one in group B. After respective follow-up of 10+/-2.8 (group A) and 9.9+/-2.7 (group B) months, cyclophosphamide cardio toxicity (group A: N=3; group B: N=2), evolution of the left ventricular ejection fraction and arterial and pulmonary pressures did not differ in the two groups. CONCLUSION: In spite of higher cyclophosphamide doses during autologous haematopoietic stem cells transplantation than bolus treatment, cardiopulmonary toxicity appeared not increased. The ongoing European ASTIS trial will compare the respective benefits of these 2 cyclophosphamide regimens in severe Systemic sclerosis.

[Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques pour le traitement des maladies auto-immunes.

THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

Human herpes virus-8 and other risk factors for Kaposi's sarcoma in kidney transplant recipients. Groupe Cooperatif de Transplantation d' Ile de France (GCIF).

BACKGROUND: The exact reasons for the high incidence of Kaposi's sarcoma (KS) after kidney transplantation are still unknown. Immunosuppression is classically considered as the main risk factor, but the relative risk contributed by the patient's geographic origin and by human herpes virus (HHV)-8 infection still has to be determined. METHODS: We carried out a retrospective and a prospective study among kidney transplant recipients (TP) to identify the risk factors for posttransplantation KS. Each of 30 KS patients was matched with two controls to investigate the association with geographic origin, immunosuppressive regimen, HHV-8 antibodies before and after transplantation, and other infections. Among TP with new onset of KS, we prospectively evaluated HHV-8 serology and viremia in response to decreased immunosuppression. RESULTS: African and Middle East origins, past infection with hepatitis B, hemoglobin level <12 g/dl, lymphocyte count <750/mm3 at the time of diagnosis and initial use of polyclonal antilymphocyte sera were risk factors for KS. After multivariate analysis, origin in Africa or Middle East and use of antilymphocyte sera for induction remained as independent risk factors. Sixty-eight percent (17/25) of TP with HHV-8 antibodies before or after transplantation developed KS compared with 3% (1/33) of seronegative TP (P<0.00001). HHV-8 DNA was detectable in seven of nine peripheral blood mononuclear cells (PBMC) and in six of six KS lesions at diagnosis; it became negative in PBMC in three of five patients in parallel with tumor regression. CONCLUSION: African and Middle East geographic origins, HHV-8 infection before and after kidney transplantation, and initial use of polyclonal antilymphocyte sera were independent risk factors for KS. The presence of HHV-8 antibodies before or after transplantation was highly predictive of the emergence of posttransplantation KS and conferred a 28-fold increased risk of KS (odds ratio=28.4; 95% confidence interval: 4.9-279). Detection of HHV-8 DNA within PBMC and KS lesions seems related to tumor burden and evolution.

[Re-emergence of tuberculosis and socioeconomic uncertainty]. / Réémergence de la tuberculose et précarité socioéconomique.

INTRODUCTION: Infectious diseases are the main cause of morbidity and mortality among socially deprived patients. In 1988-89 the secular decrease in tuberculosis stopped in France as in other industrial countries, and new emergence of the disease has been observed since then, especially among socially deprived patients. CURRENT KNOWLEDGE AND KEY POINTS: Clinical characteristics of tuberculosis remain classical among these patients, but advanced, even historical forms of the disease, are often observed, with frequent extra-pulmonary localizations. Diagnostic and therapeutical procedures must be adapted to the patients' living conditions, including their education and social support. Directly observed therapy is rarely used in France, but the development of adequate strategies for effective primary care management with adapted cost/efficiency ratios in the respect of human rights is essential. FUTURE PROSPECTS AND PROJECTS: Early tracking down of patients lost from follow-up and detailed evaluation of treatment results and social care remain priorities.