De Novo Donor-Specific Anti-Human Leukocyte Antigen Antibody Detection in Long-Term Adult Liver Transplantation.

INTRODUCTION: Information about the consequences of de novo donor-specific anti-human leukocyte antigen (DSA) antibody development in the long term after adult liver transplantation (LT) is scarce. We conducted a cross-sectional study in LT patients with a follow-up of at least 6 years. METHODS: A total of 28 adult LT patients were included, with a median follow-up of 77 months (range, 63 to 96) and without preformed anti- human leukocyte antigen (HLA) antibodies prior to LT. The anti-HLA identification was performed with LABScreen Single Antigen, whereas the ability to fix the complement was demonstrated with C1q test (One Lambda). In both assays, a value >3.500 mean fluorescence intensity (MFI) was considered positive. The anti-HLA antibody specificities were compared with donor HLA antigens to confirm them as DSA. Hepatic fibrosis was assessed by transient elastography. RESULTS: In 5 patients (17.8%), de novo DSA were detected, all them against DQ locus. In all of these cases (100%) the complement fixation was confirmed by C1q binding. The grade of hepatic fibrosis in de novo DSA patients was significantly higher compared with No-DSA patients (13.2 ± 9.2 KPa vs 7.3 ± 3.7 KPa; P = .02). It is noteworthy that in both groups of patients the levels of liver function tests (LFT) at the time of the study were normal or near the normal range with no difference between patients with or without de novo DSA. CONCLUSIONS: Our preliminary results are consistent with those previously demonstrated in pediatric LT, where de novo DSA production and humoral response could contribute to the liver fibrosis observed in the long term after LT in pediatric patients with normal or near-normal LFT.

The excess mortality related to cardiovascular diseases and cancer among adults pharmacologically treated for diabetes--the 2001-2006 ENTRED cohort.

AIMS: To compare the 5-year mortality (overall and cause-specific) of a cohort of adults pharmacologically treated for diabetes with that of the rest of the French adult population. METHODS: In 2001, 10 000 adults treated for diabetes were randomly selected from the major French National Health Insurance System database. Vital status and causes of death were successfully extracted from the national registry for 9101 persons. We computed standardized mortality ratios. RESULTS: Over 5 years, 1388 adults pharmacologically treated for diabetes died (15% of the cohort, 32.4/1000 person-years). An excess mortality, which decreased with age, was found for both genders [standardized mortality ratio 1.45 (1.37-1.52)]. Excess mortality was related to: hypertensive disease [2.90 (2.50-3.33)], ischaemic heart disease [2.19 (1.93-2.48)], cerebrovascular disease [1.76 (1.52-2.03)], renal failure [2.14 (1.77-2.56)], hepatic failure [2.17 (1.52-3.00)] in both genders and septicaemia among men [1.56 (1.15-2.09)]. An association was also found with cancer-related mortality: liver cancer in men [3.00 (2.10-4.15)]; pancreatic cancer in women [3.22 (1.94-5.03)]; colon/rectum cancer in both genders [1.66 (1.28-2.12)]. Excess mortality was not observed for breast, lung or stomach cancers. CONCLUSIONS: Adults pharmacologically treated for diabetes had a 45% increased risk of mortality at 5 years, mostly related to cardiovascular complications, emphasizing the need for further prevention. The increased risk of mortality from cancer raises questions about the relationship between cancer and diabetes and prompts the need for improved cancer screening in people with diabetes.

Prevalence, screening and treatment of chronic kidney disease in people with type 2 diabetes in France: the ENTRED surveys (2001 and 2007).

AIMS: The study aimed to assess the prevalence, quality of screening and treatment of chronic kidney disease (CKD), and their trends between 2001 and 2007, in French adults with type 2 diabetes (T2D). METHODS: The 2007 ENTRED survey randomly selected, from French medical insurance fund databases, 8926 adults treated for diabetes who had been reimbursed at least three times over the previous 12 months for oral hypoglycaemic agents or insulin. Medical reimbursement data were extracted and two sets of questionnaires were mailed, one to all patients (48% response rate) and the other to their doctors (62%). Analyses were restricted to the 3894 responders with T2D (2232 with data from their doctors). Trends between the 2001 and 2007 ENTRED surveys were studied. RESULTS: Participants' mean age was 66 years. The prevalence of CKD was estimated to be at least 29%, based on doctors' data (missing data included). Overall, only 17% had no claims for serum creatinine measurements during the year, and 71% had no claims for albuminuria tests; nonetheless, both figures had decreased from 2001. Older people, those who lived alone and those who felt poorly informed about diabetes were more likely to have made no claims for CKD screening. Assessment of quality of care (prescribing antihypertensive treatment when indicated) was possible for 66% of responders, of whom 25% did not receive such treatment. CONCLUSION: CKD is frequently seen in patients with T2D and is likely to be underestimated because albuminuria screening remains inadequate, despite significant improvements since 2001. Further efforts are needed to improve CKD screening, patient and doctor awareness, and adequate use of antihypertensive/nephroprotective medications.

Self-monitoring of blood glucose in people with type 1 and type 2 diabetes living in France: the Entred study 2001.

OBJECTIVE: To describe the practice of self-monitoring blood glucose (SMBG) testing and to determine factors linked to SMBG in people with diabetes living in France. METHODS: The 2001 Entred study, a French national survey of people being treated for diabetes, is based on a representative sample of 10,000 adults who claimed reimbursement for oral hypoglycaemic agents and/or insulin in October to December 2001 and who were randomly extracted from the database of the major National Health Insurance System. A questionnaire was mailed to all these people and was returned by 36% of them, who were then classified into three groups: type 1 diabetes (T1D, N=235); type 2 diabetes treated with insulin (iT2D, N=635); and type 2 diabetes treated with oral hypoglycaemic agents (oT2D, N=2689). Factors associated with SMBG were analyzed using logistic regression models with a step-by-step forward approach. RESULTS: HbA(1c) was greater than or equal to 8% in 42% of people with T1D, 48% of those with iT2D and 21% of those with oTD2. Almost all of those treated with insulin performed SMBG. The frequency of self-monitoring was higher in T1D than in iT2D. In T1D, 58% of people reported they took at least three tests a day, as recommended in guidelines, which was more frequent in those who knew what HbA(1c) meant and in women. In iT2D, 74% reported that they took at least two tests a day, as recommended, and it was more frequent in those who knew what HbA(1c) meant, who reported at least one severe hypoglycaemic episode in 2001 and who received dietary advice from their practitioner. In oT2D, 38% reported using SMBG (six tests a week on average), even though no official recommendation had been provided for these patients. SMBG was also more frequent in patients being treated with multiple oral hypoglycaemic agents, in those who benefited from a waiver of co-payment due to a chronic disease and in those, who had visited a diabetes specialist in 2001, reported they knew what HbA(1c) meant, received dietary advice and reported at least one severe hypoglycaemic episode in 2001 and/or a history of diabetes complications. CONCLUSION: In France, as per the official recommendations, almost all people on insulin treatment use a SMBG device while, overall, their glucose control remains poor. More than one-third of those with oT2D regularly perform SMBG. In only 3% of people, the regular use of SMBG does not appear to be related to any special needs or events (such as insulin treatment, occurrence of severe hypoglycaemia or chronic complications).

Prevalence of macrovascular complications and cardiovascular risk factors in people treated for diabetes and living in France: the ENTRED study 2001.

AIM: The aim of this study is to estimate the prevalence of macrovascular complications and cardiovascular risk factors among people with diabetes living in France and to compare these prevalences with other national estimates. METHODS: We randomly sampled 10,000 people who received one or more reimbursements for insulin or oral hypoglycaemic treatment from the major national medical insurance system during the period October-December 2001; 3646 of the 10,000 people completed a questionnaire; for a subgroup of 1718 people, their care providers completed a medical questionnaire. RESULTS: The prevalence of diagnosed macrovascular complications was of 17% according to patients (angina or myocardial infarction, 15%; coronary revascularization, 9%) and of 20% overall, according to physicians (angina or myocardial infarction, 16%; coronary revascularization, 6%; stroke, 5%). Macrovascular complications were more frequent in people with type 2 than type 1 diabetes, reflecting an age effect. The prevalences of cardiovascular risk factors in type 1 and type 2 diabetes were: current smoking, 35 and 14%; overweight, 28 and 42%; obesity, 9 and 36%; blood pressure superior to 130/80 mmHg, 29 and 59%; LDL cholesterol superior or equal to 3.4 mmol/l, 18 and 26%, respectively. CONCLUSIONS: Compared with other European countries, elevated blood pressure is more frequent in people with diabetes living in France; compared with US estimates, the prevalence of macrovascular complications is lower, glucose control better and blood pressure control poorer in France. These data, observed in a country with widespread access to care and at low cost to the patient, nevertheless demonstrate an urgent need for improving the cardiovascular risk profile of people with type 1 and type 2 diabetes, both with and without macrovascular complications.

French medical practice in type 2 diabetes: the need for better control of cardiovascular risk factors.

AIMS: In type 2 diabetes (T2D), to describe treatments to prevent cardiovascular disease, to compare current practice to French guidelines, and to identify factors associated with recommended treatments. METHODS: In the Echantillon National Témoin Représentatif des Personnes Diabétiques (ENTRED) study, 10,000 adults treated for diabetes (any type) were randomly selected from the French National Health Insurance System database. Deliveries during the last quarter of 2001 of treatments to prevent cardiovascular disease were extracted. Questionnaires were mailed to these people and their care providers. Final populations included 3324 people with T2D and their 1553 care providers. RESULTS: Overall, 18% reported coronary heart disease (CHD) and 44% others were classified as having a high cardiovascular risk; 68% received one or more antihypertensive treatment: ACE inhibitor/angiotensin receptor blocker (ARB), 44%; diuretic, 35%; calcium channel blocker, 25%; beta-blocker, 24%. Among those receiving antihypertensive treatment, 59% had blood pressure greater than 130/80mmHg. Overall, 42% received a hypolipidaemic treatment: statin, 25%; fibrate, 18%. About half the people with a high cardiovascular risk had LDL cholesterol greater than 1g/L, but only 32% were given a statin. Among people with an abnormal albumin/creatinine ratio (11%), 59% received an ACE inhibitor/ARB. Among those with CHD, 35% received the two treatments recommended in 1999 (beta-blockers and antiplatelet agents); in multivariate analyses, this two-treatment delivery was positively associated with male gender, self-reported hypertension and consulting a cardiologist. CONCLUSION: Cardiovascular risk profiles reported by providers in T2D people are high. Despite recent progress, there is a need for major improvement in practices intended to prevent cardiovascular disease in these people, especially in those at greatest CHD risk.

Implementation of a strategy to prevent TRALI in a regional blood centre.

Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion and it is probably underdiagnosed. Human leucocyte antigen (HLA) and granulocyte antibodies are thought to play a major role, but preventive measures are difficult to implement. In our regional blood centre, we implemented a preventive strategy avoiding donor deferral. Previously, pregnant apheresis donors were screened for HLA antibodies, and those with positive results were assigned to a plasma-only protocol. Plasma from these donors and from all previously pregnant whole blood donors was diverted for protein fractionation. Plasma-poor red blood cells (in additive solution, buffy coat removed) and platelets (pools with additive solution) were prepared. Prestorage leucodepletion was also applied. We found HLA antibodies in 18.1% of previously pregnant apheresis donors, and our strategy caused a 6.0% loss of apheresis platelets, a 4.8% increase of apheresis fresh frozen plasma (FFP) and a 7.8% loss of transfusable apheresis FFP. The effect on FFP from whole blood donors could be compensated. The platelet preparation method reduced the mean volume of plasma from each donor to 24.4 mL. Fifteen months after the start of our strategy, no cases of TRALI have been reported. Our experience shows that a practical strategy to prevent TRALI is feasible.

Splenectomy for poor graft function after allogeneic bone marrow transplantation in patients with chronic myeloid leukemia.

We report four patients with chronic myeloid leukemia (CML) that showed poor graft function after a non-T-depleted bone marrow transplantation (BMT) from an HLA-compatible sibling donor and who were successfully treated with splenectomy. Conditioning was done with cyclophosphamide (CY) and total body irradiation (TBI) without additional splenic irradiation. Three patients had enlarged spleens before BMT. The nucleated cell dose infused ranged from 2.3-3.2 x 10(8)/kg. Bone marrow (BM) examination prior to splenectomy showed BM aplasia (three cases) or hypocellularity (one case). At splenectomy no patient had evidence of cytomegalovirus (CMV) infection or severe acute GVHD; and three patients had moderately enlarged spleens. All patients were transfusion dependent. Complete hematological recovery was obtained in all patients. BM cellularity was normal 1 month after splenectomy. Complete chimerism of donor origin was documented. The four patients are alive (+16 to +58 months after BMT). Thus, in patients with CML, a poor graft function may be successfully corrected by splenectomy.

Invasive pulmonary aspergillosis prior to BMT in acute leukemia patients does not predict a poor outcome.

Eight patients with acute leukemia (AL) and invasive pulmonary aspergillosis (IPA) developing during previous antileukemic therapy underwent BMT (autologous in 6 cases and allogeneic 2). IPA was treated prior to BMT with full doses of amphotericin B, associated with surgical resection in three cases. One patient was treated with amphotericin B and itraconazole. Prior to BMT, seven patients had minimal residual pulmonary lesions. All patients received amphotericin B (0.5 mg/kg/day) during the aplastic period prior to engraftment. One patient died of Gram-negative septic shock before engraftment. Seven patients achieved complete hematological engraftment without any evidence of IPA reactivation. Amphotericin B was well tolerated with only minimal transient renal dysfunction in three patients. Later pulmonary complications related to IPA were observed in only one patient who developed a self-limited episode of hemoptysis. One patient died of CMV pneumonitis and two of leukemia relapse. Four patients survive disease-free and without complications related to IPA. We conclude that the reactivation of correctly treated IPA can be successfully prevented in BMT patients by use of prophylactic amphotericin B. With this approach, prior IPA is not a contraindication to BMT.