Geographical variation of disease manifestations in systemic sclerosis: a report from the EULAR Scleroderma Trials and Research (EUSTAR) group database.

BACKGROUND: Systemic sclerosis (SSc) is a vasculopathy with increased tissue deposition of collagen. The aetiology is unknown. Genetic and environmental susceptibility factors have been implicated. It is unknown whether disease presentation varies within Europe. AIMS AND METHODS: The baseline data of all SSc patients entered in the EULAR Scleroderma Trials and Research (EUSTAR) database up to April 2007 were analysed for geographical differences with regard to organ involvement, and geographical clusters with regard to clinical subsets (diffuse vs limited SSc) and autoantibodies (anticentromere vs anti-Scl70). RESULTS: 3661 patients from 79 centres in 62 cities and 23 countries were analysed. There was no clear trend between geographical coordinates and SSc subsets, although there appeared to be an increased prevalence of Scl70 in the more eastern centres. There was no association between geographical longitude or latitude and the age at the onset of Raynaud's phenomenon or the onset of non-Raynaud's symptoms. There was also a trend for the more eastern centres to care for patients with a higher prevalence of more severe organ manifestations (pulmonary arterial hypertension, cardiac involvement). Between different centres within one city there was a large variability in the frequency of organ complications. CONCLUSION: This analysis suggests that eastern centres care for more severe SSc manifestations in Europe. Large differences in patient referral account for a large local variability of SSc presentations and preclude the identification of genetic or environmental factors.

[Immunoablation and autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis]. / Intensification thérapeutique et autogreffe de cellules souches hématopoïétiques pour le traitement de la sclérose en plaques.

Numerous pathophysiological arguments supporting immunosuppression for multiple sclerosis have been collected during recent years. The relevance of intense immunosuppression, in terms of clinical benefit and early or late risk, remains a matter of discussion. Immunoablation followed by autologous hematopoietic stem cell transplantation (AHSCT) in multiple sclerosis uses intense immunosuppression, followed by reinjection of AHSC, a rescue procedure for the induced aplasia. This method targets disappearance of the immune disorder, and thus, in theory, the interruption of the disease course. Use of AHSCT to treat several types of autoimmune diseases has been performed with contrasted results. In multiple sclerosis, the experience has been gained over the past 10 years through short series of patients treated at a late stage of their disease. This article highlights the recent data of this particular treatment option in multiple sclerosis as well as the therapeutic aims that should be investigated in further trials.

[Splenic sarcoidosis diagnosed by US-guided biopsy: About a case]. / Sarcoïdose splénique diagnostiquée par biopsie écho-guidée : à propos d'un cas.

INTRODUCTION: Splenic localisation of sarcoidosis is common but rare as unique location. We report a case diagnosed by US-guided biopsy. OBSERVATION: A 42-year-old woman presented atypic and recidivant epigastric pain. Abdominal ultrasound showed splenic hypoechoic nodules not characterizable with CT or MRI. PET-CT revealed hypermetabolism without any other abnormal metabolic activity. US-guided biopsy with small needle achieved diagnosis of isolated splenic sarcoidosis. CONCLUSION: Diagnosis of splenic nodular sarcoidosis can be challenging without any other localization. Splenic biopsy achieved diagnosis. This procedure is associated with a low risk of complications - in particular hemorragic ones. Diagnostic splenectomy should be an exceptional intervention.

[Venous thromboembolism associated with long-term use of central venous catheters in cancer patients]. / Thromboses sur cathéter central chez le patient cancéreux.

OBJECTIVES: Increased incidence of cancers and the development of totally implanted venous access devices that contain their own port to deliver chemotherapy will lead to a greater than before numbers of central venous catheter related thrombosis (CVCT). Medical consequences include catheter dysfunction and pulmonary embolism. Compared with lower extremity deep venous thrombosis (DVT) (3 d) and with non CVC associated thrombosis (5 d), CVCT is associated with an increased duration of hospitalisation (9 d). CVCT oftentimes leads to the need to replace such ports at an average cost of 4500 euros. CURRENT KNOWLEDGE AND KEY POINTS: Vessel injury caused by the procedure of CVC insertion is the most important risk factor for development of CVCT. This event could cause the formation of a fresh thrombus, which is reversible in the large majority of patients. The incidence of CVC-related DVT assessed by venography has been reported to vary from 30 to 60% but catheter-related DVT in adult patients is symptomatic in only 5% of cases. The majority of patients with CVC-related DVT is asymptomatic or has non-specific symptoms: arm or neck swelling or pain, distal paresthesias, headache, congestion of subcutaneous collateral veins. In the case of clinical suspicion of CVC-related DVT, compressive ultrasonography (US), especially with Doppler and color imaging, currently is first used to confirm the diagnosis. The main criteria of color-Doppler US are visualization of mural thrombi or incompressibility of the veins. Consequently, contrast venography is reserved for clinical trials and difficult diagnostic situations. There is no consensus on the optimal management of patients with CVC-related DVT. Treatment of CVC-related VTE requires a 5- to 7-day course of adjusted-dose unfractionated heparin or LMWH followed by oral anticoagulants. Long-term LMWH that has been shown to be more effective than oral anticoagulant in cancer patients with lower limb DVT could be used in these patients. The optimal duration of oral anticoagulation treatment for CVC-related DVT is unknown, but patients with active cancer should be treated for at least 6 months or indefinitely. FUTURE PROSPECTS AND PROJECTS: The efficacy and safety of pharmacologic prophylaxis for CVC related thrombosis is not established. Additional studies performed in high risk populations are needed to define if LMWH or oral anticoagulation is indicated in this clinical setting.

Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT).

Hematopoietic stem cell transplantation (HSCT) is used with increasing frequency in Europe with 40 000 transplants reported in 2014. Transplant-related mortality remains high in allogeneic HSCT (10-20%); high-dose chemotherapy is toxic and demanding for patients. Drug development is accelerating and with limited toxicity of some targeted drugs may replace HSCT, whereas others may function as a 'bridge to transplant'. We analyzed HSCT reported to the activity survey for selected diseases in which major advances in drug development have been made. Tyrosine kinase inhibitors markedly changed the number of allogeneic HSCT in early CML. In myelodysplastic syndromes, hypomethylating agents show no effect on HSCT activity and Janus kinase inhibitors for myeloproliferative neoplasm appear to have only a temporary effect. For CLL autologous HSCT decreased after publication of trials showing improved PFS but no overall survival advantage and allogeneic rates are dropping after the introduction of Bruton kinase and PI3K Inhibitors. Whether these are 'game changers' as was imatinib for CML requires additional follow-up. For myeloma, proteasome inhibitors and new immunomodulatory drugs do not appear to impact transplant rates. Drug development data show different effects on HSCT use; highly effective drugs may replace HSCT, whereas other drugs may improve the patient's condition to allow for HSCT.

[Venous thromboembolism and cancer]. / Maladie veineuse thromboembolique et cancer.

OBJECTIVES: The risk of venous thrombosis during cancer is largely increased especially in case of chemotherapy, surgery, advanced stage disease, coagulation abnormalities. Survival of patients with cancer experiencing venous thrombosis seems to be worse. Although thrombosis may be a presenting feature of occult malignancy, there are insufficient data to support a more extensive screening than comprehensive medical history, physical examination, routine laboratory tests and chest radiography. CURRENT KNOWLEDGE AND KEY POINTS: Pathophysiology of venous thrombosis during cancer is unspecific: venous stasis, vessel wall damage, hypercoagulability). Other factors like platelet abnormalities or the direct responsibility of chemotherapy or hormonotherapy have recently been though to play a causative role. Treatment of cancer-associated thrombosis usually requires at least 6 months of low-molecular-weight heparin therapy rather than oral anticoagulant. Inferior vena cava filters are not indicated. Primary prophylaxis of thrombosis during cancer could safely been achieved with low-molecular-weight heparin. Central venous catheters can be associated with thrombotic complications. Many risks factors have been identified: catheter's type, modalities of catheter's implantation, type of perfusion, bulky mediastinal mass... Prophylactic anticoagulation is not routinely recommended. FUTURE PROSPECTS AND PROJECTS: Knew oral anticoagulants could facilitate the treatment of venous thrombosis occurring during cancer in the next years.

Low-molecular-weight heparins for cancer-associated thrombosis: Adherence to clinical practice guidelines and patient perception in TROPIQUE, a 409-patient prospective observational study.

PURPOSE: Data on long-term treatment with low-molecular-weight heparins (LMWH) in cancer patients treated for venous thromboembolism are scarce. Study objectives were to document the long-term clinical use of LMWH and patient perception in this setting. METHODS: Adult cancer patients receiving antineoplastic treatment or palliative care and LMWH for cancer associated venous thromboembolism (CAT) were eligible to participate in this prospective observational study. Main outcome was adherence to clinical practice guidelines based on recommended LMWH treatment doses for at least 3months in the absence of severe renal insufficiency. Patients' perception of the treatment was assessed in an ancillary study using the Perception Anticoagulant Treatment Questionnaire (PACT-Q). RESULTS: Among 409 included cancer patients aged 65±12.1years, overall adherence to practice guidelines as defined in the protocol was 55.3% (226 patients). However, 98.0% of patients received a prescription for 3months or more and mean LMWH treatment duration for VTE was 6.27±0.15months which meets guidelines recommendations. Main patients' expectations scored on a 1-5 scale were blood clots prevention (mean 3.94±0.75), symptom relief (mean 3.98±1.04) and ease of use (mean 4.22±0.9). LMWH treatment appeared convenient (global score 79.7±17.1 on a 0 to 100 scale) and 69.1% of patients were satisfied or very satisfied. CONCLUSION: Despite incomplete strict adherence to guidelines, treatment duration with LMWH was adequate showing substantial progress in the management of CAT patients. Patients expectations were high while treatment was perceived convenient with a high degree of satisfaction.

Major bleeding complications in patients treated with direct oral anticoagulants: One-year observational study in a Paris Hospital.

Direct oral anticoagulants (DAOC) are indicated for the treatment of venous thromboembolism and the prevention of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Given their advantages and friendly use for patient, the prescription of long term DOAC therapy has rapidly increased both as first line treatment while initiating anticoagulation and as a substitute to vitamins K antagonist (VKA) in poorly controlled patients. However, DOAC therapy can also be associated with significant bleeding complications, and in the absence of specific antidote at disposal, treatment of serious hemorrhagic complications under DOAC remains complex. We report and discuss herein five cases of major hemorrhagic complications under DOAC, which were reported to the pharmacological surveillance department over one year at Saint-Louis University Hospital (Paris, France). We further discuss the need for careful assessment of the risk/benefit ratio at time of starting DOAC therapy in daily clinical practice.

Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually.

A record number of 40 829 hematopoietic stem cell transplantation (HSCT) in 36 469 patients (15 765 allogeneic (43%), 20 704 autologous (57%)) were reported by 656 centers in 47 countries to the 2014 survey. Trends include: continued growth in transplant activity, more so in Eastern European countries than in the west; a continued increase in the use of haploidentical family donors (by 25%) and slower growth for unrelated donor HSCT. The use of cord blood as a stem cell source has decreased again in 2014. Main indications for HSCT were leukemias: 11 853 (33%; 96% allogeneic); lymphoid neoplasias; 20 802 (57%; 11% allogeneic); solid tumors; 1458 (4%; 3% allogeneic) and non-malignant disorders; 2203 (6%; 88% allogeneic). Changes in transplant activity include more allogeneic HSCT for AML in CR1, myeloproliferative neoplasm (MPN) and aplastic anemia and decreasing use in CLL; and more autologous HSCT for plasma cell disorders and in particular for amyloidosis. In addition, data on numbers of teams doing alternative donor transplants, allogeneic after autologous HSCT, autologous cord blood transplants are presented.

[Setting up a data collection and assessment system of the Permanent Healthcare Access Activities (PASS)]. / Mise en place d'un système de recueil et d'évaluation de l'activité médicosociale des permanences d'accès aux soins de santé (PASS).

INTRODUCTION: Five years after introducing the Permanent Access to Healthcare activity (PASS), it became necessary to analyse how it works. MATERIAL AND METHODS: A computerized data collection and assessment system intended to evaluate the PASS health activities has been set up in 11 University Hospitals and ten General Hospitals. From January 1st to June, 30th 2003 data was captured in a computer. RESULTS: The patients requiring medical advice are young (with an average age of 35 years) and present several signs of poverty in terms of accommodation, social relationships and financial means. Besides, almost all of them are uninsured. The PASS public corresponds completely to the created system. Poverty risk factors vary according to the geographic origin. Indeed, French people often suffer from isolation, whereas foreign patients present financial problems. The major part of patients are foreigners and more than a third of them do not speak French, which is an additional obstacle to care. Most of the time, the PASS patients present digestive disorders, nevertheless there are some differences between French and foreign patients. Indeed, foreigners very frequently have digestive and osteoarticluar problems, whereas French patients suffer from psychic disorders and present addictive behaviours. Some patients are sent to physicians downtown (9%) and to external medicosocial assistance centres (39.5%). DISCUSSION: This study (first one in France) provides us with homogenous data regarding the activities of PASS centres nationwide. The usefulness of computers and its acceptability facilitate data diffusion, with possibilities of adapting to each centre while preserving a common basis.

Hematopoietic SCT in Europe 2013: recent trends in the use of alternative donors showing more haploidentical donors but fewer cord blood transplants.

A record number of 39,209 HSCT in 34,809 patients (14,950 allogeneic (43%) and 19,859 autologous (57%)) were reported by 658 centers in 48 countries to the 2013 survey. Trends include: more growth in allogeneic than in autologous HSCT, increasing use of sibling and unrelated donors and a pronounced increase in haploidentical family donors when compared with cord blood donors for those patients without a matched related or unrelated donor. Main indications were leukemias, 11,190 (32%; 96% allogeneic); lymphoid neoplasias, 19,958 (57%; 11% allogeneic); solid tumors, 1543 (4%; 4% allogeneic); and nonmalignant disorders, 1975 (6%; 91% allogeneic). In patients without a matched sibling or unrelated donor, alternative donors are used. Since 2010 there has been a marked increase of 96% in the number of transplants performed from haploidentical relatives (802 in 2010 to 1571 in 2013), whereas the number of unrelated cord blood transplants has slightly decreased (789 in 2010 to 666 in 2013). The use of donor type varies greatly throughout Europe.

Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015.

This is the sixth special report that the European Society for Blood and Marrow Transplantation regularly publishes on the current practice and indications for haematopoietic SCT for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred in the field of haematopoietic SCT over the last years. Cord blood units as well as haploidentical donors have been increasingly used as stem cell sources for allo-SCT, thus, augmenting the possibility of finding a suitable donor for a patient. Continuous refinement of conditioning strategies has also expanded not only the number of potential indications but also has permitted consideration of older patients or those with co-morbidity for a transplant. There is accumulating evidence of the role of haematopoietic SCT in non-haematological disorders such as autoimmune diseases. On the other hand, the advent of new drugs and very effective targeted therapy has challenged the role of SCT in some instances or at least, modified its position in the treatment armamentarium of a given patient. An updated report with revised tables and operating definitions is presented.

[Perception of organ grafts by internists]. / Perception de l'activité de greffe d'organe par les médecins internistes.

INTRODUCTION: At the time when organ transplantation occupies a preponderant place in the treatment of many pathologies, the role of the internist in the care of grafted patients remains confidential and poorly defined. PATIENTS AND METHODS: A questionnaire was sent to 730 internist practitioners. The aims of this questionnaire were to evaluate 1) their level of knowledge and practice of transplantation; 2) their declared interest on the subject; and finally 3) their perception of the theoretical place of the internists in the transplantation. RESULTS: Two hundred twenty-five answered. Although nearly 80% of the practitioners who answered this investigation declared themselves interested in the subject of transplantation, more than 60% considered their theoretical and practical knowledge on the subject to be insufficient. Nearly 70% said they felt ill at ease when faced with a grafted patient in consultation. Nearly two experts out of three considered that the role of the internist in the follow-up of grafted patients should be reinforced but less than 50% of them wished to be more involved, directly and personally. DISCUSSION: Whereas grafted patients frequently suffer from polypathologies that could be treated in internal medicine, a majority of internists do not wish to be directly implicated and/or do not feel qualified to treat these patients. The inherent risk in this is to see this specialty gradually excluded from the care networks available to grafted patients.

[Venous thromboembolism and cancer]. / Maladie thromboembolique veineuse et cancer.

INTRODUCTION: Thromboembolic venous disease, which includes both peripheral venous thrombosis and pulmonary embolism, is a frequent disorder in patients with cancer. Although thromboembolic manifestations may precede the diagnosis of cancer, the value of extensive clinical search for potential underlying cancer when faced with venous thromboembolic manifestations has not been demonstrated. CURRENT KNOWLEDGE AND KEY POINTS: Clinical and biological studies have demonstrated that acquired abnormalities in blood hemostasis, especially procoagulant factors, account for the onset of thromboembolic manifestations in patients with cancer. Classical anticoagulant therapy is associated with low efficacy and tolerance in patience with cancer who are at high risk for hemorrhagic complications and recurrence of thromboembolic disease. FUTURE PROSPECTS AND PROJECTS: Recent data suggest the value of anticoagulant therapy using either low molecular weight heparin or warfarin at low doses (INR < 2) according to the specific surgical or medical context.

[A malarial attack on return from a voyage to the French Antilles. Discussion of the mode of transmission]. / Accés palustre au retour d'un voyage aux Antilles françaises. Discussion du mode de transmission.

Malaria has been considered to be eradicated from the French West Indies for over 25 years. In this report we describe a patient who was hospitalized and successfully treated in Paris for severe Plasmodium falciparum malaria after returning form a brief trip to Guadeloupe. Several modes of transmission are possible. Given the presence of a reservoir of Plasmodium falciparum gametocytes in the Haitian immigrant community and persistent breeding of Anopheles albimanus in the French West Indies, the most likely explanation is local transmission. This is the second case of malaria involving travelers to Guadeloupe to be reported within the last ten years and the first time that autochtonous transmission has been considered. Falciparum malaria should be included in differential diagnosis for patients presenting fever after returning from travel in the French West Indies, a highly popular tourist destination.

Hematopoietic SCT in Europe: data and trends in 2012 with special consideration of pediatric transplantation.

In all, 661 of 680 centers in 48 countries reported 37 818 hematopoietic SCT (HSCT) in 33 678 patients (14 165 allogeneic (42%), 19 513 autologous (58%)) in the 2012 survey. Main indications were leukemias, 10 641 (32%; 95% allogeneic); lymphoid neoplasias, 19 336 (57%; 11% allogeneic); solid tumors, 1630 (5%; 3% allogeneic); and nonmalignant disorders, 1953 (6%; 90% allogeneic). There were more unrelated donors than HLA-identical sibling donors (54% versus 38% (8% being mismatched related donor HSCT)). Cord blood was almost exclusive in allogeneic transplants (5% of total). Since 2011, the highest increases in allogeneic HSCT were for AML in CR1 (12%) and for myeloproliferative neoplasm (15%). For autologous HSCT the main increases were for plasma cell disorders (7%), non-Hodgkin lymphoma (4%) and autoimmune disease (50%). There were 4097 pediatric patients <18 years of age receiving HSCT, 2902 received an allogeneic and 1195 an autologous HSCT. Overall, 69% of allogeneic and 64% of autologous HSCT were performed in dedicated pediatric centers and the remainder in combined adult and pediatric centers. Distributions of diseases, donor types and stem cell source for all patients and pediatric patients in particular are shown. A percentage of centers fulfilling the annual required criteria for patient numbers for JACIE accreditation are provided.

Hematopoietic SCT in Europe: data and trends in 2011.

In all, 651 from 680 centers in 48 countries reported 35 660 hematopoietic SCT (HSCT) in 32 075 patients (13 470 allogeneic (42%), 18 605 autologous (58%)) to the 2011 survey. Main indications were: leukemias; 10 113 (32%; 94% allogeneic); lymphoid neoplasias; non-Hodgkin's lymphoma, Hodgkin's lymphoma, plasma cell disorders; 18 433 (57%; 12% allogeneic); solid tumours; 1573 (5%; 5% allogeneic); and non-malignant disorders; 1830 (6%; 92% allogeneic). There were more unrelated donors than HLA identical sibling donors (54% versus 39%); proportion of peripheral blood as stem cell source was 99% for autologous and 73% for allogeneic HSCT. Cord blood was only used in allogeneic transplants (6% of total). In the past 10 years, the overall number of transplants has increased by 53%. Allogeneic HSCT have doubled (from 7272 to 14 549) while, autologous have increased by 32% and continue to increase by about 1100 HSCT per year since 2001. In the past 2 years, an increase of >2000 HSCT per year was seen. Transplant activity is shown by team size. For allogeneic HSCT, we show use of reduced-intensity conditioning versus myeloablative conditioning across Europe and use of post-transplant donor lymphocyte infusions with considerable variation across different countries.