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1.
Blood ; 124(18): 2858-66, 2014 Oct 30.
Article in English | MEDLINE | ID: mdl-25232056

ABSTRACT

Antiplatelet-antibody-producing B cells play a key role in immune thrombocytopenia (ITP) pathogenesis; however, little is known about T-cell dysregulations that support B-cell differentiation. During the past decade, T follicular helper cells (TFHs) have been characterized as the main T-cell subset within secondary lymphoid organs that promotes B-cell differentiation leading to antibody class-switch recombination and secretion. Herein, we characterized TFHs within the spleen of 8 controls and 13 ITP patients. We show that human splenic TFHs are the main producers of interleukin (IL)-21, express CD40 ligand (CD154), and are located within the germinal center of secondary follicles. Compared with controls, splenic TFH frequency is higher in ITP patients and correlates with germinal center and plasma cell percentages that are also increased. In vitro, IL-21 stimulation combined with an anti-CD40 agonist antibody led to the differentiation of splenic B cells into plasma cells and to the secretion of antiplatelet antibodies in ITP patients. Overall, these results point out the involvement of TFH in ITP pathophysiology and the potential interest of IL-21 and CD40 as therapeutic targets in ITP.


Subject(s)
Antibody Formation/immunology , B-Lymphocytes/pathology , Blood Platelets/immunology , Cell Differentiation/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , Spleen/pathology , T-Lymphocytes, Helper-Inducer/cytology , Adult , Aged , Antibody Formation/drug effects , Antigens, CD/metabolism , B-Lymphocyte Subsets/immunology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Blood Platelets/drug effects , CD40 Ligand/metabolism , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Female , Germinal Center/pathology , Humans , Immunoglobulin G/biosynthesis , Interleukins/pharmacology , Lymphocyte Count , Male , Middle Aged , Phenotype , Plasma Cells/drug effects , Plasma Cells/metabolism , Plasma Cells/pathology , Purpura, Thrombocytopenic, Idiopathic/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , T-Lymphocytes, Helper-Inducer/drug effects , T-Lymphocytes, Helper-Inducer/immunology
2.
Rheumatology (Oxford) ; 54(11): 2071-5, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26163690

ABSTRACT

OBJECTIVE: To investigate the validity of the global APS score (GAPSS) to predict thrombosis in patients with autoimmune diseases. METHODS: This prospective cohort study included consecutive patients with aPL or SLE. aPL, aPS-PT and GAPSS were determined. A Cox proportional hazards model assessed the validity of GAPSS and identified other potential independent predictors of thrombosis. RESULTS: One hundred and thirty-seven patients [43.5 (s.d. 15.4) years old; 107 women] were followed up for a mean duration of 43.1 (s.d. 20.7) months. Mean GAPSS was significantly higher in patients who experienced a thrombotic event compared with those without [10.88 (s.d. 5.06) vs 8.15 (s.d. 5.31), respectively, P = 0.038]. In univariate analysis, age [hazard ratio (HR) = 1.04 (95% CI 1.01, 1.08)] and GAPSS above 16 [HR = 6.86 (95% CI 1.90, 24.77)] were each significantly associated with thrombosis during follow-up, while history of arterial thrombosis [HR = 2.61 (95% CI 0.87, 7.82)] failed to reach significance. Among aPL assays, IgG aPS/PT--a component of the GAPSS--was significantly associated with thrombosis [HR = 2.95 (95% CI 1.02, 8.51)]. In multivariate analysis, GAPSS above 16 remained the only significant predictor of thrombosis [HR = 6.17 (95% CI 1.70, 22.40)]. CONCLUSION: This first external validation study confirmed that GAPSS can predict thrombosis in patients with aPL and associated autoimmune diseases.


Subject(s)
Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Severity of Illness Index , Thrombosis/epidemiology , Adult , Autoimmune Diseases/complications , Autoimmune Diseases/diagnosis , Cohort Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Prospective Studies , Risk Factors
3.
Blood ; 122(14): 2477-86, 2013 Oct 03.
Article in English | MEDLINE | ID: mdl-23963041

ABSTRACT

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8(+) T-cell frequency. Moreover, in the RTX- nonresponder patient group, the CD8(+) T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8(+) T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8(+) T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Drug Resistance/immunology , Lymphocyte Activation/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/therapeutic use , Female , Humans , Immunohistochemistry , Immunologic Factors/therapeutic use , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Real-Time Polymerase Chain Reaction , Rituximab , Spleen/immunology , Young Adult
4.
J Neurol Neurosurg Psychiatry ; 86(2): 216-21, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24780954

ABSTRACT

BACKGROUND: Giant cell arteritis (GCA) is the most common vasculitis in people ≥50 years and can be associated with stroke. We aimed to evaluate the epidemiology and characteristics of stroke in patients with GCA. METHODS: All patients with a biopsy-proven diagnosis of GCA were identified among residents of the city of Dijon, France (152 000 inhabitants), between 2001 and 2012 using a prospective database. Among these, patients who suffered from stroke were retrieved by crossing data from the population-based Dijon Stroke Registry. Demographics and clinical features were recorded. We considered that the stroke was GCA-related if the stroke revealed GCA or occurred between the onset of symptoms and 4 weeks after the start of treatment. RESULTS: Among the 57 biopsy-proven patients with GCA (incidence rate 10.9/100 000/year in individuals ≥50 years), 4 (7.0%) experienced a GCA-related stroke. Three were men and all had ≥2 vascular risk factors and were ≥80 years. The stroke was vertebrobasilar for 3/4 patients and undetermined for the remaining one. The incidence rate of GCA-related stroke in patients ≥50 years was 0.76/100 000/year (95% CI 0 to 2.47), 1.36/100 000/year in men (95% CI 0 to 3.63) and 0.33/100 000/year (95% CI 0 to 1.45) in women. CONCLUSIONS: This population-based study demonstrated that GCA-related stroke essentially affects the vertebrobasilar territory and mainly occurs in old men with associated vascular risk factors. Although rare, GCA symptoms must be searched for in elderly patients with stroke, and optimal vascular prevention must be conducted carefully in patients with GCA with a high vascular risk before initiating GCA treatment.


Subject(s)
Giant Cell Arteritis/epidemiology , Stroke/epidemiology , Age Distribution , Aged , Aged, 80 and over , Female , France/epidemiology , Giant Cell Arteritis/complications , Humans , Incidence , Male , Middle Aged , Prospective Studies , Registries , Sex Factors , Stroke/complications
5.
Blood ; 118(16): 4394-400, 2011 Oct 20.
Article in English | MEDLINE | ID: mdl-21876120

ABSTRACT

Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.


Subject(s)
Antibodies, Monoclonal, Murine-Derived/immunology , Immunologic Factors/immunology , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Spleen/drug effects , Adult , Aged , Antibodies, Monoclonal, Murine-Derived/therapeutic use , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Female , Humans , Immunologic Factors/therapeutic use , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/immunology , Rituximab , Spleen/cytology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Th1 Cells/drug effects , Th1 Cells/immunology
6.
Arthritis Rheum ; 64(11): 3788-98, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22833233

ABSTRACT

OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.


Subject(s)
Giant Cell Arteritis/immunology , NK Cell Lectin-Like Receptor Subfamily B/immunology , Polymyalgia Rheumatica/immunology , Th1 Cells/immunology , Th17 Cells/immunology , Adult , Aged , Cell Differentiation/immunology , Cells, Cultured , Female , Flow Cytometry , Giant Cell Arteritis/pathology , Humans , Male , Middle Aged , Polymyalgia Rheumatica/pathology , Prospective Studies , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/immunology , Th1 Cells/cytology , Th17 Cells/cytology
7.
JAMA ; 307(9): 948-55, 2012 Mar 07.
Article in English | MEDLINE | ID: mdl-22396517

ABSTRACT

CONTEXT: The only treatment available to restore normal cardiac output in patients with hereditary hemorrhagic telangiectasia (HHT) and cardiac failure is liver transplant. Anti-vascular endothelial growth factor treatments such as bevacizumab may be an effective treatment. OBJECTIVES: To test the efficacy of bevacizumab in reducing high cardiac output in severe hepatic forms of HHT and to assess improvement in epistaxis duration and quality of life. DESIGN, SETTING, AND PATIENTS: Single-center, phase 2 trial with national recruitment from the French HHT Network. Patients were 18 to 70 years old and had confirmed HHT, severe liver involvement, and a high cardiac index related to HHT. INTERVENTION: Bevacizumab, 5 mg per kg, every 14 days for a total of 6 injections. The total duration of the treatment was 2.5 months; patients were followed up for 6 months after the beginning of the treatment. MAIN OUTCOME MEASURE: Decrease in cardiac output at 3 months after the first injection, evaluated by echocardiography. RESULTS: A total of 25 patients were included between March 2009 and November 2010. Of the 24 patients who had echocardiograms available for reread, there was a response in 20 of 24 patients with normalization of cardiac index (complete response [CR]) in 3 of 24, partial response (PR) in 17 of 24, and no response in 4 cases. Median cardiac index at beginning of the treatment was 5.05 L/min/m(2) (range, 4.1-6.2) and significantly decreased at 3 months after the beginning of the treatment with a median cardiac index of 4.2 L/min/m(2) (range, 2.9-5.2; P < .001). Median cardiac index at 6 months was significantly lower than before treatment (4.1 L/min/m(2); range, 3.0-5.1). Among 23 patients with available data at 6 months, we observed CR in 5 cases, PR in 15 cases, and no response in 3 cases. Mean duration of epistaxis, which was 221 minutes per month (range, 0-947) at inclusion, had significantly decreased at 3 months (134 minutes; range, 0-656) and 6 months (43 minutes; range, 0-310) (P = .008). Quality of life had significantly improved. The most severe adverse events were 2 cases of grade 3 systemic hypertension, which were successfully treated. CONCLUSION: In this preliminary study of patients with HHT associated with severe hepatic vascular malformations and high cardiac output, administration of bevacizumab was associated with a decrease in cardiac output and reduced duration and number of episodes of epistaxis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00843440.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Arteriovenous Malformations/etiology , Cardiac Output/drug effects , Liver/blood supply , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Telangiectasia, Hereditary Hemorrhagic/physiopathology , Arteriovenous Malformations/physiopathology , Bevacizumab , Epistaxis/etiology , Epistaxis/prevention & control , Female , Heart Failure , Humans , Male , Middle Aged , Prospective Studies , Telangiectasia, Hereditary Hemorrhagic/complications , Treatment Outcome
8.
Rheumatol Int ; 31(5): 587-93, 2011 May.
Article in English | MEDLINE | ID: mdl-20039171

ABSTRACT

Churg-Strauss Syndrome (SCS) is a systemic vasculitis associated with asthma and eosinophilia. The aim of our work is to describe this pathology in the Burgundian population in France. We counted from the hospitalisation data-processing summaries, the whole of the SCS hospitalised in Burgundy between 1998 and 2008. During the follow-up, the clinical and paraclinical characteristics of every patient were collected. The average prevalence is of 11.3 per million inhabitants and the incidence is of 1.2 new cases per million inhabitants per annum. There exists however, a great prevalence disparity and incidence amongst the various departments of the area. The patient's average follow-up is of 7.7 years. In 23% of the cases one finds a starting factor for vasculitis. The delay between the first signs and the diagnostic is an average of 61 months. The ANCA are positive in 26% of cases and of anti-myeloperoxidase specificity in 83% of cases (P < 0.001). The most profitable biopsies are essentially cutaneous and neuromuscular. At the diagnostic, two-third of the patients have had a treatment adapted according to the current recommendations based on the Five Factor Score. The remission rate within a 1-year period is of 77%. The remission is strongly correlated to the therapeutic protocol associating corticoids and cyclophosphamide (P < 0.05). In conclusion, the prevalence of SCS in our area is similar to that observed in other European regions. However, this vasculitis remains a difficult and often a tardive diagnostic pathology.


Subject(s)
Churg-Strauss Syndrome/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Biopsy , Churg-Strauss Syndrome/diagnosis , Churg-Strauss Syndrome/drug therapy , Female , France/epidemiology , Guideline Adherence , Hospitalization/statistics & numerical data , Humans , Immunosuppressive Agents/therapeutic use , Incidence , Male , Middle Aged , Practice Guidelines as Topic , Prevalence , Residence Characteristics , Retrospective Studies , Survival Analysis , Survival Rate , Time Factors , Treatment Outcome , Young Adult
9.
BMC Infect Dis ; 8: 12, 2008 Jan 30.
Article in English | MEDLINE | ID: mdl-18234108

ABSTRACT

BACKGROUND: There is currently a lack of consensus for the diagnosis, investigations and treatments of acute bacterial prostatitis (AP). METHODS: The symptoms, investigations and treatments of 371 inpatients diagnosed with AP were analyzed through a retrospective study conducted in four departments - Urology (U), Infectious Diseases (ID), Internal Medicine (IM), Geriatrics (G) - of two French university hospitals. RESULTS: The cause of admission, symptoms, investigations and treatments depended markedly on the department of admission but not on the hospital. In U, patients commonly presented with a bladder outlet obstruction, they had a large imaging and functional check-up, and received alpha-blockers and anti-inflammatory drugs. In ID, patients were febrile and received longer and more appropriate antibiotic treatments. In G, patients presented with cognitive disorders and commonly had post-void urine volume measurements. In IM, patients presented with a wide range of symptoms, and had very diverse investigations and antibiotic regimen.Overall, a 3:1 ratio of community-acquired AP (CA-AP) to nosocomial AP (N-AP) was observed. Urine culture isolated mainly E. coli (58% of AP, 68% of CA-AP), with venereal agents constituting less than 1%. The probabilistic antibiotic treatments were similar for N-AP and CA-AP (58% bi-therapy; 63% fluoroquinolone-based regimen). For N-AP, these treatments were more likely to be inadequate (42% vs. 8%, p < 0.001) and had a higher rate of bacteriological failure (48% vs. 19%, p < 0.001). Clinical failure at follow-up was more common than bacteriological failure (75% versus 24%, p < 0.001). Patients older than 49 had more underlying urinary tract disorders and a higher rate of clinical failure (30% versus 10%, p < 0.0001). CONCLUSION: This study highlights the difficulties encountered on a daily basis by the physicians regarding the diagnosis and management of acute prostatitis.


Subject(s)
Bacterial Infections/diagnosis , Prostatitis/diagnosis , Prostatitis/microbiology , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/drug therapy , Community-Acquired Infections/microbiology , Cross Infection/microbiology , France , Hospitals, University , Humans , Male , Middle Aged , Prostate-Specific Antigen/blood , Prostatitis/drug therapy , Recurrence , Retrospective Studies
10.
Presse Med ; 46(12 Pt 2): e329-e338, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29150231

ABSTRACT

The discovery of hyperferritinemia is often fortuitous, revealed in results from a laboratory screening or follow-up test. The aim of the diagnostic procedure is therefore to identify its cause and to identify or rule out hepatic iron overload, in a three-stage process. In the first step, clinical findings and several simple laboratory tests are sufficient to detect four of the most frequent causes of high ferritin concentrations: alcoholism, inflammatory syndrome, cytolysis, and metabolic syndrome. None of these causes is associated with substantial hepatic iron overload. If transferrin saturation is high (> 50%), hereditary hemochromatosis will be considered in priority. In the second phase, rarer diseases will be sought. Among them, only chronic hematologic diseases (acquired or congenital) and excessive iron intake or infusions (patients on chronic dialysis and high-level athletes) are at risk of iron overload. In the third stage, if a doubt persists about the cause or if the ferritin concentration is very high or continues to rise, it is essential to verify the hepatic iron concentration to rule out overload. The principal examination to guide diagnosis and treatment is hepatic MRI to assess its iron concentration. It is essential to remember that more than 40% of patients with hyperferritinemia have several causes simultaneously present.


Subject(s)
Ferritins/metabolism , Iron Metabolism Disorders/diagnosis , Diagnostic Tests, Routine , Ferritins/blood , Humans , Iron Metabolism Disorders/blood
11.
Eur J Hum Genet ; 13(11): 1186-91, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16094309

ABSTRACT

Splenomegaly with sea-blue histiocytes, thrombocytopenia and hypertriglyceridemia is a very rare association that has been described in only one report to date. The molecular defect in the two reported patients consists in a deletion of a leucine at position 149 in the receptor-binding region of the apoE molecule. Here, we report on another family in whom the proband and his brother were diagnosed with splenomegaly, thrombocytopenia and hypertriglyceridemia. An apoE p.Leu149del mutation was found in both subjects. A large beta band in the VLDL fraction and elevated VLDL cholesterol-to-plasma triglyceride ratio was observed in the proband only. Their mother, presenting with isolated hypertriglyceridemia, also carried the same p.Leu149del mutation. The coexistence of factors facilitating the development of hypertriglyceridemia and/or low HDL-cholesterol level could explain why the proband and his brother developed a splenomegaly with thrombocytopenia, whereas the mother did not. Moreover, the presence of an apoE2 allele in the proband likely explains the more severe phenotype we observed in this subject. In conclusion, the apoE p.Leu149del mutation results in a very striking phenotype including one or all symptoms among splenomegaly, thrombocytopenia and hypertriglyceridemia, and should be considered as a differential diagnosis of storage disorders in the causes of splenomegaly with sea-blue histiocytes.


Subject(s)
Apolipoproteins E/genetics , Gene Deletion , Sea-Blue Histiocyte Syndrome/genetics , Apolipoproteins E/blood , Female , Humans , Hyperlipoproteinemia Type IV/genetics , Lipids/blood , Lipoproteins/blood , Male , Middle Aged , Pedigree , Phenotype , Splenomegaly/genetics , Syndrome , Thrombocytopenia/genetics
12.
Arch Intern Med ; 162(15): 1729-35, 2002.
Article in English | MEDLINE | ID: mdl-12153376

ABSTRACT

BACKGROUND: The use of warfarin sodium for treating venous thromboembolism in patients with cancer is associated with a significant risk of recurrence and bleeding. The use of low-molecular-weight heparin sodium for secondary prevention of venous thromboembolism in cancer patients may reduce the complication rate. OBJECTIVE: To determine whether a fixed dose of subcutaneous low-molecular-weight heparin is superior to oral warfarin for the secondary prophylaxis of venous thromboembolism in patients with cancer and venous thromboembolism. METHODS: In a randomized, open-label multicenter trial performed between April 1995 and March 1999, we compared subcutaneous enoxaparin sodium (1.5 mg/kg once a day) with warfarin given for 3 months in 146 patients with venous thromboembolism and cancer. MAIN OUTCOME MEASURE: A combined outcome event defined as major bleeding or recurrent venous thromboembolism within 3 months. RESULTS: Of the 71 evaluable patients assigned to receive warfarin, 15 (21.1%; 95% confidence interval [CI], 12.3%-32.4%) experienced one major outcome event compared with 7 (10.5%) of the 67 evaluable patients assigned to receive enoxaparin (95% CI, 4.3%-20.3%; P =.09). There were 6 deaths owing to hemorrhage in the warfarin group compared with none in the enoxaparin group. In the warfarin group, 17 patients (22.7%) died (95% CI, 13.8%-33.8%) compared with 8 (11.3%) in the enoxaparin group (95% CI, 5.0%-21.0%; P =.07). No difference was observed regarding the progression of the underlying cancer or cancer-related death. CONCLUSIONS: These results confirm that warfarin is associated with a high bleeding rate in patients with venous thromboembolism and cancer. Prolonged treatment with low-molecular-weight heparin may be as effective as oral anticoagulants and may be safer in these cancer patients.


Subject(s)
Anticoagulants/therapeutic use , Embolism/prevention & control , Heparin, Low-Molecular-Weight/therapeutic use , Neoplasms/complications , Neoplasms/drug therapy , Venous Thrombosis/prevention & control , Warfarin/therapeutic use , Adult , Aged , Aged, 80 and over , Dose-Response Relationship, Drug , Embolism/mortality , Endpoint Determination , Female , Follow-Up Studies , Hemorrhage/chemically induced , Humans , International Normalized Ratio , Male , Middle Aged , Neoplasms/mortality , Recurrence , Survival Analysis , Treatment Outcome , Venous Thrombosis/mortality
13.
Eur J Intern Med ; 16(6): 387-90, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16198895

ABSTRACT

Systemic mastocytosis (SM) refers to a group of heterogeneous diseases that can be divided into indolent SM, for which prognosis is favorable, and malignant SM, which has a poor prognosis. While the diagnosis of SM is often a challenge since clinical and biological abnormalities are not specific, prognosis is even more difficult to predict. Thus, we aimed to highlight predictable factors in a cohort of 28 cases of SM. Among the 13 women and 15 men studied were 7 patients who had an aggressive form of SM that ultimately led to death in 3 of them. We found common characteristics among these seven patients. First, they were older when the first symptoms appeared and when the diagnosis was confirmed. Second, ascitis, lymphadenopathy, anemia, and thrombocytopenia were significantly more frequent, while cutaneous lesions and flush were less frequent. Moreover, general symptoms, gastrointestinal disorders, neutropenia, and coagulation abnormalities also seemed to characterize this group of patients. Understanding the factors that predict SM is essential in order to provide patients with the malignant form of the disease with specific treatments.

14.
Therapie ; 60(4): 391-9, 2005.
Article in French | MEDLINE | ID: mdl-16268439

ABSTRACT

BACKGROUND: The risks associated with drug use are not confined to adverse reactions. Failures can occur in the process of drug prescribing, dispensing and administration. Such preventable events are termed 'medication errors'. Errors in preparation and administration, the last step in the medication process, constitute a good indicator of the quality of the medication process, and are irredeemable. METHODS: A protocol for measuring errors in the preparation and administration of medication has been developed and used in an internal medicine department at the University Hospital of Dijon. RESULTS: This protocol has enabled several different rates of medication errors to be determined depending on the calculation approach used: 15.1% with respect to interventions by nurses, 41% relating to the total number of opportunities for error, and 8.8% with respect to a methodological problem analysed in the study. The potential clinical significance, incidence and causes of errors during the medication process were also analysed. DISCUSSION AND CONCLUSION: Medical errors are not detected in our health system and are thus not preventable. Their consequences are incompatible with a well organised treatment process. The rate of medication errors is therefore a good indicator of the quality of the medication system in a hospital that is following the current steps for risk reduction and accreditation.


Subject(s)
Drug Compounding , Drug-Related Side Effects and Adverse Reactions , Medication Errors , Pharmaceutical Preparations/administration & dosage , France , Humans , Risk
15.
Presse Med ; 33(19 Pt 1): 1319-22, 2004 Nov 06.
Article in French | MEDLINE | ID: mdl-15615237

ABSTRACT

OBJECTIVE: To assess the activity of a short-lived orientation unit (SLO) with 9 beds that only receives patients from the emergency department in whom diagnosis and/or specific treatment must be set-up while awaiting a vacant bed in the appropriate medical department. METHODS: During the 29 months after the creation of the SLO (Feb. 2001 to June 2003), we analysed the parameters supplied every month by the medical computer department: number of patients hospitalized in the SLO, age, gender, principle diagnosis according to the PMSI coded data, duration of hospitalisation, number of deaths, number of releases direct to home, number of transfers to a specialized unit and qualification of the referral units. RESULTS: 1840 patients (mean age: 73 years) were hospitalized in this unit. The most frequent diseases were bronchopneumonia (16%), syncope episode (14%), cerebral stroke (12%), thromboembolic diseases (11%) and heart failure (10%). The mean duration of hospitalization was 3.7 days (less than 48 hours in 46% of cases). In 40% of cases, patients were able to return directly to their homes. In 62% of cases, the patients were referred to a specialised unit within 48 hours. The functioning of the SLO has various specificities (repeated personalised telephone contacts, letters for rapid transfer, difficult co-operation with certain departments...). CONCLUSION: The SLO is useful for patients since it accelerates their adapted management and allows quick transfer to the unit adapted to their pathology, permitting correct adequation between the pathologies of the patients and the competence of the specialised medical unit.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Hospitalization/statistics & numerical data , Internal Medicine , Patient Admission , Patient Transfer , Aged , Female , Hospital Mortality , Humans , Male , Referral and Consultation
16.
Rev Prat ; 53(5): 489-94, 2003 Mar 01.
Article in French | MEDLINE | ID: mdl-12722605

ABSTRACT

The systemic changes induced by inflammation have been referred as the acute-phase response. The changes in the concentrations of acute-phase proteins are due largely to changes in their production by hepatocytes induced by pro-inflammatory cytokines. Because of its specificity, sensibility and short half-life, C-reactive protein is the most useful indicator among all the acute-phase proteins. The clinical strategy to deal with an acute-phase response is to search the aetiology: infections, neoplasms, auto-immune and allergic diseases. The treatment of an acute-phase response is the treatment of its aetiology.


Subject(s)
Acute-Phase Proteins/pharmacology , Acute-Phase Reaction/physiopathology , Acute-Phase Reaction/etiology , Acute-Phase Reaction/therapy , Autoimmune Diseases/complications , Half-Life , Humans , Infections/complications , Neoplasms/complications
17.
Eur J Intern Med ; 25(9): 837-42, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25307285

ABSTRACT

BACKGROUND: Although secondary hypogammaglobulinemia is more frequent than primary hypogammaglobulinemia, its etiology and management are poorly described, particularly for mild hypogammaglobulinemia. METHODS: This retrospective observational study included all adult patients with a gammaglobulin level <6.4g/L on serum electrophoresis identified at Dijon teaching hospital between April and September 2012. Clinico-biological features, etiologies and infectious complications were collected at inclusion and compared between group 1 (gammaglobulin <5g/L, severe hypogammaglobulinemia), and group 2 (gammaglobulin <6.4 and ≥5g/L, mild hypogammaglobulinemia). RESULTS: Among the 4011 serum electrophoreses, 570 samples from 389 patients had gammaglobulin levels below 6.4g/L: 156 (40%) in group 1 and 233 (60%) in group 2. Mean age±SD was 67 (15) years, and sex ratio was 1.04 (M/F) with no difference between the two groups. An etiology was identified in 79% and 58% of patients in groups 1 and 2, respectively (p<0.0001). The main etiologies were similar in both groups and included malignant hemopathy treated with cytostatic agents (n=129, 33%), smoldering or newly-diagnosed hemopathy without treatment (n=49, 13%) and immunosuppressive treatment (n=91, 23%). The incidence of hypogammaglobulinemia-related infections was 22/100/year, with no significant difference between the two groups (p=0.17). Vaccination coverage against pneumococcus was 33%, and higher in group 1 (46% vs. 24%; p<0.0001). When no cause was known at inclusion, an etiology was discovered in 22/130 patients (17%), 11 in each group. CONCLUSIONS: Though mild hypogammaglobulinemia does not meet the classical criteria for hypogammaglobulinemia (<5g/L), the etiology and infectious risk are similar. It therefore requires investigation and vaccination.


Subject(s)
Agammaglobulinemia/therapy , Agammaglobulinemia/complications , Agammaglobulinemia/diagnosis , Agammaglobulinemia/etiology , Aged , Electrophoresis , Female , Humans , Infections/etiology , Infections/immunology , Male , Pneumococcal Vaccines/therapeutic use , Retrospective Studies , Severity of Illness Index
18.
Arch Gerontol Geriatr ; 55(1): 101-5, 2012.
Article in English | MEDLINE | ID: mdl-21868109

ABSTRACT

Only few studies have investigated the use of HA in elderly subjects and there are no data in very elderly subjects. We assessed the prescription of HA and analyzed the relationship between such prescriptions and frailty markers among persons aged 80 and more in an observational study. We recorded the prescriptions for 13,211 patients aged 80-109 years and affiliated to the "Mutualité-Sociale-Agricole (MSA)" of Burgundy over a 1-month period. The prescription of a HA among all included patients, and the existence of serious long-term disease(s) (LTD), polypharmacy or a prescription of cardiovascular drugs among patients receiving a HA were recorder. Among the 13,211 patients, 3412 aged 80-98 years were treated with an HA. The main HA were statins (70.4%), and fibrates were used in 27.3% of cases. Of these 3412 patients, 2250 had one or several LTD mainly coronaropathy, hypertension, diabetes mellitus or peripheral artery disease. The mean number of drugs per prescription was 6.37. Among subjects treated with HA, 40% also received antiplatelets, 35.6% ß-blockers and 30% inhibitors of the renin-angiotensin system. For 99% of the patients, the prescription of HA was a renewal. Prescribers were mainly general practitioners (96.8%). Statins are the most widely prescribed HA even among very elderly subjects. However, after 80 years the prescription of HA, mainly statins, decreases with aging. This could be explained by polypathology, polypharmacy and the deterioration in metabolic functions which are markers of frailty. This study should encourage research into the use of statins in very elderly subjects.


Subject(s)
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , Adrenergic beta-Antagonists/therapeutic use , Aged, 80 and over , Cardiovascular Agents/therapeutic use , Coronary Artery Disease/drug therapy , Diabetes Mellitus/drug therapy , Drug Prescriptions , Female , Fibric Acids/therapeutic use , France , Humans , Hypertension/drug therapy , Male , Peripheral Arterial Disease/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Polypharmacy
19.
Presse Med ; 40(4 Pt 1): e163-72, 2011 Apr.
Article in French | MEDLINE | ID: mdl-21255964

ABSTRACT

PURPOSE: The ankle brachial pressure index (ABPI) makes it possible to diagnose peripheral artery disease (PAD) and identify patients with a vascular risk. Recently, the Haute Autorité de santé (HAS) issued guidelines. We wanted to determine the interest and impact of these guidelines when applied to patients hospitalised in an internal medicine department. METHODS: We systematically measured the ABPI in two internal medicine departments. We compared the results obtained with the screening criteria and the good practices recommended by the HAS. RESULTS: The screening criteria recommended by the HAS were already applied in 91% of our 97 patients. PAD was found in 37.1% of patients. In 83% of cases, the diagnosis was unknown (p = 0.02). The PAD was symptomatic in 83% of the known PAD cases, and 3.3% in newly-diagnosed cases (p < 0.001)). The sensitivity of the HAS screening criteria applied to our population was 100% but almost patients justifies ABPI screening. The specificity was 11.5%, the positive predictive value 40% and the negative predictive value 100%. The optimal treatment recommended was implemented in only 50% of patients with known arteriopathy and in 10% of newly-diagnose PAD (p = 0.04). CONCLUSION: PAD prevalence is high in internal medicine department and systematic measurement of ABPI is effective. Determining patients to screen with the HAS criteria has a poor impact in our patients. The optimal treatment is still extremely under-prescribed even in patients with known PAD.


Subject(s)
Ankle Brachial Index , Arterial Occlusive Diseases/diagnosis , Guideline Adherence , Ischemia/diagnosis , Mass Screening/methods , Adolescent , Adrenergic beta-Antagonists/therapeutic use , Adult , Aged , Aged, 80 and over , Arterial Occlusive Diseases/drug therapy , Arterial Occlusive Diseases/physiopathology , Blood Glucose/metabolism , Calcium Channel Blockers/therapeutic use , Comorbidity , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/drug therapy , Diabetic Angiopathies/physiopathology , Female , France , Hospital Departments , Humans , Hyperlipidemias/diagnosis , Hyperlipidemias/drug therapy , Hyperlipidemias/physiopathology , Intermittent Claudication/diagnosis , Intermittent Claudication/drug therapy , Intermittent Claudication/physiopathology , Internal Medicine , Ischemia/drug therapy , Ischemia/physiopathology , Leg/blood supply , Lipids/blood , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies , Reference Values , Risk Factors , Vasodilator Agents/therapeutic use , Young Adult
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