Ambulatory blood pressure monitoring and left ventricular hypertrophy: correlations and trial of predictive value]

The purpose of the study is to make a selection of patients with left ventricular hypertrophy from Ambulatory Blood Pressure Monitoring (ABPM) values. We studied 39 patients, 23 men and 16 women, without treatment. These patients had systolic pressure > 140 mmHg and/or diastolic pressure > 90. With ABPM we measured mean systolic (MS) and diastolic (MD) pressure during the day (D) and the night (N), the percentages of systolic values (%S) > 160 mmHg and of diastolic values (%D) > 95 mmHg. With echocardiography we measured left ventricular mass index (LVMI: Devereux) and with pulsed Doppler peak of early (E) and late (A) ventricular filling and the ration A/E. We found the same amount of correlations between ABPM and echocardiographic parameters as other authors. [table: see text] The study of LVMI found a difference between groups when MD were > 140/90 (*) and A was significantly greater in patients with MSD > 140 (*). LVMI was greater in patients with MDD > 80 (*) and A was greater in patients with MSN > 120 (*). Predictive value of MSD > 140: 53% specificity: 79%. Predictive value of MSN > 120: 80% specificity: 45.8%. We concluded that the correlations between ABPM and echocardiographic disturbances are not very strong, but significant. If the predictive value of MSF is low, his specificity is rather high and conversely MSN has a good predictive value for selection of hypertrophic patients.     

Recombination pattern of the TCR γ locus in human peripheral T-cell lymphomas

The recombination events of the γ and β T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ-gene rearrangement while only 18/23 showed a concomitant β-gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ- and β-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ-rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ-locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.     

Management of lower urinary tract fibroepithelial polyps in children

IntroductionFibroepithelial polyps (FEP) of the lower urinary tract are relatively common in adults but rare in children, with fewer than 250 cases reported in the literature to date.ObjectiveThe aim of this study was to address the experience of FEP management in children.Study designA retrospective multicenter review was undertaken in children with defined FEP of the lower urinary tract managed between 2008 and 2018. The data at 18 pediatric surgery centers were collected. Their demographic, radiological, surgical, and pathological information were reviewed.ResultsA total of 33 children (26 boys; 7 girls) were treated for FEP of the lower urinary tract at 13 centers. The most common presentation was urinary outflow as hematuria (41%), acute urinary retention (25%), dysuria (19%), or urinary infections (28%). A prenatal diagnosis was made for three patients with hydronephrosis. Almost all of the children (94%) underwent ultrasound imaging of the urinary tract as the first diagnostic examination, 23 (70%) of them also either had an MRI (15%), cystourethrography (25%), computerized tomography (6%), or cystoscopy (45%). Two of these children (6%) had a biopsy prior to the surgery. The median preoperative delay was 7.52 (range: 1–48) months. Most of the patients were treated endoscopically, although four (12.1%) had open surgery and two (6.1%) had an additional incision for specimen extraction. The median hospital stay was 1.5 (range: 1–10) days. There were no recurrences and no complications after a median follow-up of 13 (range: 1–34) months.DiscussionThe main limitation of our study is the retrospective design, although it is the largest one for this pathology.ConclusionThis series supports sonography as the most suitable diagnosis tool before endoscopy to confirm the diagnosis and to perform the resection for most FEP in children. This report confirms the recognized benign nature in the absence of recurrences.Level of EvidenceLevel V.     

Localized pelvic neuroblastoma: excellent survival and low morbidity with tailored therapy--the 10-year experience of the French Society of Pediatric Oncology.

PURPOSE: To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). PATIENTS AND METHODS: All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. RESULTS: Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% +/- 4% and 84% +/- 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). CONCLUSION: Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.     

Référentiel d’enseignement de la transfusion sanguine aux étudiants techniciens de laboratoire de biologie médicale

Purpose of the studyThe new French law about clinical laboratory medicine, the requirements of the ISO/CEI 15189 standard, the numerous abilities expected from the medical laboratory technologists and their involvement in blood bank management has led the working group “Recherche et démarche qualité” of the French Society of Blood Transfusion to initiate an inventory of blood transfusion teaching syllabus for medical laboratory technology students and to propose transfusion medicine teaching guidelines.Material and methodsSeven worksheets have been established for that purpose including red blood cell antigen typing and antibody screening, blood sampling in immunohaematology, automation, clinical practices, blood products, blood delivery and haemovigilance.ResultsThese guidelines aim at contributing to the harmonization of transfusion medicine teaching and at providing objective elements to the medical laboratory managers regarding the practical and theoretical skills of theirs collaborators.     

The Bulle: Support and Prevention of Psychological Decompensation of Health Care Workers During the Trauma of the COVID-19 Epidemic

The coronavirus disease 2019 pandemic presents unprecedented challenges for the health care system. The pressure on health care staff continues to intensify, accentuated by the confinement (lockdown) of the population and the unprecedented duration of this emergency. Separately and especially together, overwork, degraded conditions of care because of the never-ending emergency, and the risk of exposure to the virus can lead to acute psychological distress or signs of burnout.This original program was developed at Cochin Hospital in Paris, France to prevent these potentially dramatic psychological consequences, support the medical staff, and identify those most affected to offer them specific care. A program and a space for relaxation and support for hospital caregivers by hospital caregivers, the Port Royal Bulle (the Bubble) offers these workers help in decompression and relaxation. It combines a warm and caring welcome that promotes attention, listening, conversations, and exchanges as needed, empathetic support, and the ability to participate in soothing, relaxing, or low-impact physical activities. It takes care of caregivers. The Bubble is a program that is simple to set up and that appears to meet professionals' expectations. Making it permanent and enlarging its scale, as a complement to existing programs, might help to support health care personnel in their work.     

RhoB prenylation is driven by the three carboxyl-terminal amino acids of the protein: evidenced in vivo by an anti-farnesyl cysteine antibody

Protein isoprenylation is a lipid posttranslational modification required for the function of many proteins that share a carboxyl-terminal CAAX motif. The X residue determines which isoprenoid will be added to the cysteine. When X is a methionine or serine, the farnesyl-transferase transfers a farnesyl, and when X is a leucine or isoleucine, the geranygeranyl-transferase I, a geranylgeranyl group. But despite its CKVL motif, RhoB was reported to be both geranylgeranylated and farnesylated. Thus, the determinants of RhoB prenylation appear more complex than initially thought. To determine the role of RhoB CAAX motif, we designed RhoB mutants with modified CAAX sequence expressed in baculovirus-infected insect cells. We demonstrated that RhoB was prenylated as a function of the three terminal amino acids, i.e., RhoB bearing the CAIM motif of lamin B or CLLL motif of Rap1A was farnesylated or geranylgeranylated, respectively. Next, we produced a specific polyclonal antibody against farnesyl cysteine methyl ester allowing prenylation analysis avoiding the metabolic labeling restrictions. We confirmed that the unique modification of the RhoB CAAX box was sufficient to direct the RhoB distinct prenylation in mammalian cells and, inversely, that a RhoA-CKVL chimera could be alternatively prenylated. Moreover, the immunoprecipitation of endogenous RhoB from cells with the anti-farnesyl cysteine antibody suggested that wild-type RhoB is farnesylated in vivo. Taken together, our results demonstrated that the three last carboxyl amino acids are the main determinants for RhoB prenylation and described an anti-farnesyl cysteine antibody as a useful tool for understanding the cellular control of protein farnesylation.     

Bezafibrate lowers very long-chain fatty acids in X-linked adrenoleukodystrophy fibroblasts by inhibiting fatty acid elongation

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding ALDP, an ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane. ALDP deficiency results in impaired peroxisomal β-oxidation and the subsequent accumulation of very long-chain fatty acids (VLCFA; > C22:0) in plasma and tissues. VLCFA are primarily derived from endogenous synthesis by ELOVL1. Therefore inhibiting this enzyme might constitute a feasible therapeutic approach. In this paper we demonstrate that bezafibrate, a PPAR pan agonist used for the treatment of patients with hyperlipidaemia reduces VLCFA levels in X-ALD fibroblasts. Surprisingly, the VLCFA-lowering effect was independent of PPAR activation and not caused by the increase in either mitochondrial or peroxisomal fatty acid β-oxidation capacity. In fact, our results show that bezafibrate reduces VLCFA synthesis by decreasing the synthesis of C26:0 through a direct inhibition of fatty acid elongation activity. Taken together, our data indicate bezafibrate as a potential pharmacotherapeutic treatment for X-ALD. A clinical trial is currently ongoing to evaluate the effect in patients with X-ALD.