Search

Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Societe Francophone d’Histocompatibilite et d’Immunogenetique (SFHI)

International audience; Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already beenpublished. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006–2012).Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the FrenchSociety for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading toa low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignantdiseases remained significant risk factors (P = 0.04 and Po0.0001, respectively). In multivariate analysis, only status of disease was asignificant risk factor (Po0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/orHLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their rolewas more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio = 0.57[0.32–1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

International audience; We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.Bone Marrow Transplantation advance online publication, 3 November 2014; doi:10.1038/bmt.2014.253.

Purpose To assess the safety, efficacy, predictability and stability of photorefractive keratectomy in compound myopic astigmatism with a moderate and high cylinder component. Methods Photorefractive keratectomy was done in 42 eyes with compound myopic astigmatism with the spherocylindrical algorithm of the MEL-70 excimer laser, with wide ablation zones. Results Spherical equivalent refraction changed from -4.19 +/- 1.65D to -0.05 +/- 0.31D, refractive cylinder from -2.01 +/- 0.71D to -0.09 +/- 0.20D and mean sphere from -3.22 +/- 1.76D to -0.02 +/- 0.26D. Mean uncorrected visual acuity rose from 0.12 +/- 0.17 to 0.91 +/- 0.10. No eye lost lines of spectacle-corrected visual acuity. The safety index was 1.03 and the efficacy index 0.98. Six months from the treatment all eyes were within +/- 1D, 8.9% of eyes were within 0.50D and 44% were plano of target refraction. Refractive and topographical stability were achieved between one and three months after treatment. Transient haze was observed between one and three months after PRK. Conclusions Photorefractive keratectomy with the MEL-70 excimer laser to correct myopic astigmatism was a safe and effective procedure with good stability at six months' follow-up. Refractive and visual outcome confirmed that excellent predictability can be expected.

OBJECTIVE: To evaluate four-dimensional contrast-enhanced ultrasound (4D-CEUS) as an alternative imaging method to computed tomography angiography (CTA) during follow up of fenestrated endovascular aneurysm repair (FEVAR) for juxta- and para-renal abdominal aortic aneurysms (AAA). METHODS: Between October 2011 and March 2012, all consecutive patients who underwent FEVAR follow up were included in the study and evaluated with both 4D-CEUS and CTA. The interval between the two examinations was always ≤ 30 days. Endpoints were the comparison of postoperative AAA diameter, AAA volume, presence of endoleaks, revascularized visceral vessel (RVV) visualization, and patency. Comparative analysis was performed using Bland-Altman plots and McNemar's Chi-square test. RESULTS: Twenty-two patients (96% male, 4% female; mean age 74 ± 7 years; American Society of Anesthesiologists grade III/IV 82%/18%) were enrolled. Seventy-eight RVV (fenestrations: 60; scallops: 17; branches: 1) were analyzed. The mean AAA diameter evaluated by 4D-CEUS and CTA was 45 ± 10 mm (range 30-69 mm) and 48 ± 9 mm (range 32-70 mm), respectively. The mean difference was 3 ± 3 mm. The mean AAA volume evaluated by 4D-CEUS and CTA was 150 ± 7 cc (range 88-300 cc) and 159 ± 68 cc (range 80-310 cc), respectively. The mean difference was 7 ± 4 cc; a Bland-Altman plot revealed agreement in AAA diameter and volume evaluation (p < .01) between 4D-CEUS and CTA. The observed agreement for the detection of endoleaks was 95%. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent (p > .05) at detecting endoleaks. The first segment of six (8%) RVVs (four renal and two superior mesenteric arteries) was not directly visualized by 4D-CEUS owing to obesity, but the contrast enhancement into the distal part of vessel or into the relative parenchyma gave indirect information about their patency. McNemar's Chi-square test demonstrated the superiority of CTA (p = .031) in visualizing RVVs. The patency of 77/78 RVVs was confirmed with both techniques. McNemar's Chi-square test confirmed that 4D-CEUS and CTA were equivalent in their ability to detect visceral vessel patency. CONCLUSIONS: The data suggest that 4D-CEUS is as accurate as CTA in the evaluation of postoperative AAA diameter and volume, endoleak detection, and RVV patency after FEVAR. Four-dimensional CEUS could provide hemodynamic information regarding RVVs, and reduce radiation exposure and renal impairment during follow up. Obesity limits the diagnostic accuracy of 4D-CEUS

Objective. To establish by means of ultrasound and magnetic resonance imaging (MRI) the role of tenosynovitis and arthritis in determining the “sausage-like” aspect of finger dactylitis and to compare the results of the 2 examinations. Methods. Twelve dactylitic fingers and their corresponding normal contralateral fingers belonging to 10 patients who met the Amor criteria for the diagnosis of seronegative spondylarthropathy (SpA) were studied by ultrasonography and MRI. Results. MRI revealed a significant increase in the volar bone-to-skin distance in dactylitic fingers with respect to that of the normal contralateral fingers (P < 0.001). This increase was due to distension of the flexor synovial sheaths (P < 0.00001) by fluid collection. Peritendinous soft tissues were not involved, since these were found to be significantly thicker in the normal fingers (P < 0.05). Of the 36 joints of the 12 dactylitic fingers, only 1 showed capsule distension. Using MRI as the “gold standard,” ultrasonography showed a 100% sensitivity and specificity for flexor tenosynovitis, but lacked sensitivity for joint involvement because it failed to reveal joint capsule distension in the only joint involved. Similarly, physical examination showed a 100% sensitivity and specificity for flexor sheath involvement. Conclusion. Dactylitis is due to flexor tenosynovitis. Enlargement of the finger joint capsule is not an indispensable condition for the “sausage-like” feature. Physical examination is a sufficient method for the diagnosis of dactylitis.

Although significant steps have been taken to monitor complex hemodynamics in neonatal and pediatric intensive care units, cardiovascular function in neonates is still evaluated by measuring blood pressure, heart rate, diuresis, central venous pressure (if a central venous catheter was placed), capillary refill time and oxygen saturation measurement in the upper and lower extremities. The use of other non-invasive or invasive technologies (for example, continuous impedance cardiography, transesophageal Doppler and continuous pulse contour methods) is, in fact, quite problematic in neonates in whom relevant hemodynamic changes are common during the transition to postnatal life. For these reasons, use of transthoracic echocardiography, performed by skilled pediatric intensivists, is increasing in several dedicated centers to guide treatment choices in hemodynamically unstable neonates.

We describe the identification of the novel human leukocyte antigen (HLA) blank allele A*2901102 N which was detected in an individual of mixed race. The serological HLA class I typing was A1; B7,44 whereas PCR-SSP indicated the presence of an additional A*29 allele. The pedigree analysis demonstrated that the new blank allele segregated with the haplotype A*29null B*07, inherited from the individual's Vietnamese father. A single G--Tau transversion was detected at position 1 of intron 4, which is a highly conserved nucleotide position in vertebrate splice donor sites. Accordingly, it is very likely that this nucleotide exchange inhibits the splicing of intron 4, resulting in a premature stop codon further downstream. Despite this alteration, transcription into mRNA was demonstrated.

Annulo-aortic ectasia is a dilation of the aortic root with the involvement of the Valsalva sinuses. In 1968 Bentall and DeBono proposed to replace the aortic valve, the Valsalva sinuses and the ascending aorta with a composite tube graft containing aortic valve prosthesis. Consequently coronary ostia had to be reimplanted on the prosthetic tube. Recently the use of new materials has resulted in a more acceptable operative risk, and postoperative bleeding and late mortality have been reduced.From January 1991 to December 1998, 44 out of 241 patients were operated on with the Bentall-DeBono procedure, affected by dissecting or expansive aneurysm of the ascending aorta. Of the 44 patients (35 males, 9 females, mean age 53.7 years), 3 presented with acute aortic dissection, 5 were asymptomatic, 10 were in NYHA functional class II, 14 in class III, 9 in class IV, and 2 in CCS class 4; 1 patient had dysphonia; 37 patients presented with isolated aortic regurgitation, and 7 associated aortic valvular stenosis. The diagnosis of acute dissection was made by transesophageal echocardiography and that of expansive aneurysm by thorax helical computed tomographic scanning and/or magnetic resonance imaging and cardiac catheterization. Follow-up was obtained in 100% of the patients for an average of 23 +/- 20.9 months (range 4-79 months).Four patients (9%) died; in 4 patients (9%) postoperative bleeding needed reoperation, in 5 (11.4%) a permanent pacemaker for atrioventricular block was implanted, and 1 patient (2.3%) had transient hemiparesis. At univariate analysis predictive factors for operative risk were NYHA functional class IV (p0.005) and atherosclerotic etiology (p0.05). At follow-up 7 late deaths occurred for an actuarial survival at 24 months of 75 +/- 9%. Causes were sudden death in 3 patients, cardiac failure in 3 and stroke in 1 patient; 31 surviving patients (94%) were in NYHA functional class I and 2 patients in class II (6%).The Bentall-DeBono procedure involves moderate risk with good results; clinical presentation and associated valvular pathology influence early and mid-term results.

Atrial septal aneurysm can be associated with other cardiovascular diseases such as atrial septal defect, patent ductus arteriosus, pulmonary hypertension and cerebrovascular events (transient ischemic attack or stroke). The introduction of transthoracic and more recently transesophageal echocardiography allowed for a more frequent observation of this pathology and also suggested that atrial septal aneurysm is a risk factor for cerebral ischemia. However, the pathophysiological pathway is still unclear. In January 1997 a 33-year-old man was admitted to our hospital because of atrial septal aneurysm and a previous cerebrovascular event. Magnetic resonance imaging revealed a cerebrovascular malformation and transesophageal echocardiography confirmed the presence of atrial septal aneurysm. We hypothesize that a common etiopathogenetic pathway may cause both the cardiac and cerebrovascular anomaly and that the latter may be responsible alone for cerebral ischemic events; thus in the presence of an atrial septal aneurysm associated with a cerebrovascular malformation, a conservative medical approach may be the treatment of choice.

This article describes a new aortic Dacron conduit that has been designed for use in all types of surgery of the aortic root. Its use is aimed at facilitating the surgical procedure and obtaining a natural anatomical configuration of the aortic root.The modified Dacron conduit is obtained by adding a smaller piece of Dacron tube that is resilient in the horizontal plane to one end of a standard Dacron conduit. Upon implantation, this small piece of Dacron conduit will stretch in the horizontal plane creating pseudosinuses and a new sinotubular junction. This modified conduit has been used in 4 cases for a Bentall operation in association with a mechanical or a biological valve, in 4 cases in a Yacoub type of valve sparing procedure and in 1 case in a David type I of valve sparing procedure. All patients had aortic root aneurysm with severe aortic regurgitation. There were 6 males and 3 females with a mean age of 61 +/- 16 years. In most cases a 28 mm Dacron conduit was used.All surgery was carried out without mortality or morbidity. The creation of pseudosinuses was confirmed intraoperatively by visual inspection. Transesophageal echocardiography in patients who had undergone the Bentall operation showed a normally functioning valve prosthesis with a suitably shaped aortic root. In patients who had undergone the valve sparing procedures it showed a competent aortic valve, the creation of pseudosinuses of normal shape and depth, and the presence of a well defined sinotubular junction. Angiography confirmed that the prosthetic aortic root perfectly resembled the normal root anatomy.This modified new aortic root conduit appears to perfectly reproduce a normal root anatomy without the need of modifying the original techniques.

Classic experimental studies have shown that in the presence of a flow-limiting coronary artery stenosis, myocardial ischemia during metabolic or pharmacological arteriolar vasodilation causes wall motion abnormalities, which precede electrocardiographic (ECG) changes in the myocardial regions supplied by the stenotic branch. The aim of this study was to establish whether in patients with chronic stable angina the regional distribution of wall motion changes and sequence of ischemic events are similar to that observed in experimental models, as currently believed.The study population consisted of 20 men and 4 women (mean age 59 +/- 10 years) who were recruited on the basis of the following criteria: 1) a history of chronic stable angina without clinical and instrumental evidence of previous myocardial infarction; 2) reproducible positive exercise tests for ECG myocardial ischemia and anginal pain; 3) angiographically normal left ventricular function; 4) isolated stenosis of the left anterior descending coronary artery (LAD). Patients underwent continuous 12-lead ECG and echocardiographic monitoring during dipyridamole infusion.During dipyridamole infusion 3 patients (13%) did not develop echocardiographic changes, ECG changes or angina, 14 (58%) exhibited ECG changes, 18 (75%) lamented angina and 16 (67%) developed echocardiographic changes. In 5 of these 16 patients (31.5%) echocardiographic changes occurred in LAD-dependent territories only, in 5 they occurred in non-LAD-dependent territories only (31.5%) and in 6 (37%) they occurred in both LAD- and non-LAD-dependent territories. A total of 14 patients exhibited both echocardiographic and ECG changes and/or angina. In 6 of these 14 patients (43%) echocardiographic changes were the first ischemic events; in the remaining 8 patients (57%) ECG changes and/or angina were the first ischemic events.In the majority of patients during dipyridamole infusion regional wall motion changes occur in territories supplied by non-stenotic coronary artery branches; they are probably caused, therefore, by distal vessel dysfunction. Furthermore, the sequence of ischemic events is different in individual patients. These findings indicate that in stable angina the mechanisms of ischemia are multiple and that the link between coronary stenoses and myocardial ischemia is very elusive.

Transrectal guided biopsy is the method of choice to detect carcinoma of the prostate. Systematic bilateral biopsies have been recently introduced in clinical practice because they provide valuable information about the local staging of the cancer and better representation of the actual Gleason grade of the whole tumor. The purpose of this study is to assess the frequency of neoplastic lesions in prostatic areas with normal structure at US and rectal examination and to identify, if possible, some criteria to be used in the selection of patients for random biopsies.Systematic bilateral prostatic biopsies were performed in 155 patients with elevated prostate specific antigen (PSA) values, not exceeding 40 ng/mL and with suspected neoplastic unilateral lesion at rectal examination or US. All patients with bilateral or diffuse nodules were not included in this analysis. Three random biopsies for every side of the gland were performed using a 16-18 gauge tru-cut needle. A direct biopsy of the hypoechoic nodule or area was always performed. All specimens results were correlated with PSA and PSA density values obtained before biopsy.Systematic biopsy identified cancers in 53/155 patients (34.19%). Of 53 cases, 35 (66%) had unilateral prostatic carcinoma and 18 (34%) had bilateral cancer. The final diagnosis was benign prostatic lesion in the remaining 102 patients (benign prostatic hyperplasia, nonspecific granulomatous prostatitis, chronic prostatitis). Dividing all the patients into main groups on the basis of pathologic findings (benign, unilateral and bilateral carcinoma) there was a statistically significant difference of PSA values between the 3 groups.Our observations confirm the utility of systematic US-guided biopsies in the detection of tumors in normal appearing areas at US and transrectal examination, but the clinical utility of this approach needs further confirmation. Additional data on cancer volume, Gleason grade, capsular infiltration, lymph node metastasis and long term survival must be evaluated with large number of patients. In our experience PSA values can be used as a criterion to select the patients to submit to this technique to provide useful, preoperative information suspected prostatic malignancy.

The cause of musculoskeletal symptoms in the proximal extremities of patients who have polymyalgia rheumatica is not completely understood. The diffuse and severe discomfort can only be partially explained by the mild joint synovitis that is observed in these patients.To determine the involvement of the synovial structures of the shoulder girdle of patients who have active symptoms of polymyalgia rheumatica.Case-control study.2 secondary referral centers of rheumatology.13 case-patients who had active symptoms of polymyalgia rheumatica seen during a 6-month period, 9 control-patients who had early symptoms of elderly-onset rheumatoid arthritis, and 10 age-matched healthy controls.Magnetic resonance imaging of the shoulder was done on the 13 case-patients, 9 control-patients, and 10 healthy controls.The frequency of subacromial and subdeltoid bursitis was significantly higher in the case-patients (who had polymyalgia rheumatica) than in the control-patients (who had elderly-onset rheumatoid arthritis). The frequencies of synovitis of the joints and tenosynovitis of the biceps did not significantly differ between the 13 case-patients and the 9 control-patients. None of the healthy controls showed evidence of fluid accumulation in the joints, bursae, or sheaths of the long head of the biceps.Inflammation of subacromial and subdeltoid bursae in association with synovitis of the glenohumeral joints and tenosynovitis of the biceps may contribute to the diffuse discomfort in the shoulder girdle observed in patients with polymyalgia rheumatica.

To investigate using magnetic resonance imaging (MRI) the part played by flexor and extensor tenosynovitis and synovitis of the metatarsophalangeal (MTP), proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints in producing the "sausage-like" aspect of spondyloarthropathy (SpA) toe dactylitis.Twelve sausage-like toes and corresponding contralateral toes of 7 consecutive patients meeting Amor criteria for SpA were studied by MRI.All dactylitic toes showed fluid collections in the flexor synovial sheaths on MRI. Due to the sheath distension the plantar bone to skin distance was significantly increased (p0.05) in the dactylitic toes compared to normal contralateral toes. Peritendinous soft tissues were not involved since these were significantly thicker (p0.05) in normal toes. Extensor synovial sheaths were involved in only 4 dactylitic toes. Of the 36 joints of the 12 dactylitic toes only 2 MTP joints showed capsule distension. Considering MRI as the "gold standard", examination showed 100% sensitivity and specificity for flexor sheath involvement but lacked sensitivity for extensor synovial sheaths and showed a low specificity for joint capsule distension.Like finger dactylitis, toe dactylitis may also be due to flexor tenosynovitis and synovitis of MTP, PIP, and DIP joints may not be a required condition for sausage-shaped appearance. Extensor tenosynovitis may be present in addition to flexor tenosynovitis. Physical examination is a sufficient method for diagnosing toe dactylitis.

E2/CD99 is a 32-kDa transmembrane molecule that does not belong to any known family of proteins. It appears to regulate adhesion properties of T cells as previously reported, in particular, the induction of homotypic adhesion in CD4+ CD8+ thymocytes. Apoptosis induced via E2/CD99 displays characteristic morphologic features, but includes early mitochondrial alterations and phosphatidylserine exposure at the outer leaflet of the plasma membrane. It is not followed by detectable DNA fragmentation, and its time course is much longer than apoptosis induced via the Fas/CD95 pathway. It requires 18 h for completion. E2/CD99-induced apoptosis does not require any RNA or protein synthesis and still occurs following blockage of the Fas pathway. It is, however, dependent on CPP32 and IL-1beta-converting enzyme-type cysteine proteases, as shown by blockade with their respective specific inhibitors. This effect is restricted to double-positive thymocytes carrying an intermediate density of CD3 and including all CD69+ cells. Thus, E2/CD99 apears to mediate a distinctive apoptotic signal at a critical stage of thymocyte differentiation, i.e., when positive selection is known to occur.

Human herpesvirus 6 (HHV-6) infection is common and occurs early in life, causing exanthema subitum (roseola)1 and an acute febrile illness without rash in young children. 2,3 HHV-6 infection has recently been implicated as a major cause of febrile convulsions in children 4 and acute HHV-6 infections account for 10 to 20% of all febrile children seen in pediatric emergency departments. 3 Serious complications have been described including disseminated infection, 5 meningitis, 6 encephalitis, 7,8 fulminant hepatitis 9,10 and fatal hemophagocytic syndrome.11 This report presents two cases of neonatal hepatitis associated with a primary infection with HHV-6 that could possibly have resulted from an ante- or perinatal transmission.

Increased morbidity and mortality occur in diabetics with kidney disease. The decrease in fixed anionic charges is considered an early abnormality occurring well before any clinical sign of disease. It has been attached importance to the study of protein charge-selectivity decreased in diabetes in order to find the parameters which highlight the initial preclinical stage of diabetic nephropathy. To investigate the role of protein charge in early diabetic proteinuria, the clearance of protein differing in charge and/or size (anionic and cationic IgG, albumin) was evaluated in type 1 diabetic patients: 18% of them showed increased values of albuminuria. Anionic and total IgG clearances significantly increased in 30% and 12% of the patients and were correlated with the duration of the disease. The anionic/cationic IgG clearance ratio tended to increase in parallel with albumin clearance, but once above macroalbumonuric levels, it tended to fall again, indicating the concomitant presence of size-selectivity loss. In addition to albumin excretion, the anionic IgG clearance and the anionic/cationic IgG ratio, may be valuable in assessing early kidney protein charge-selectivity impairment and in better characterizing normoalbuminuric patients and those in the preclinical stage of diabetic nephropathy.

OBJECTIVE: Prostatic abscesses are uncommon in clinical practice because early antibiotic therapy has reduced complications of prostatitis. Prostatic abscess mainly affects diabetic and immunosuppressed patients. The organisms most frequently involved are Escherichia coli and Staphylococcus, whereas gonococcus is rarely encountered. The results in eight men with prostatic abscess, five of whom were treated with sonographically guided percutaneous drainage, are reported. The diagnosis, clinically suspected in only three patients, was confirmed by transrectal sonography. All patients experienced complete abscess resolution. CONCLUSION: Transrectal sonography is the most reliable imaging method to diagnose prostatic abscess. Percutaneous transperineal or transrectal drainage is the first choice for therapy because of the lower risk of complication compared with surgery.