Multicentric study underlining the interest of adding CD5, CD7 and CD56 expression assessment to the flow cytometric Ogata score in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms

Although numerous recent publications have demonstrated interest in multiparameter flow cytometry in the investigation of myelodysplastic disorders, it is perceived by many laboratory hematologists as difficult and expensive, requiring a high level of expertise. We report a multicentric open real-life study aimed at evaluating the added value of the technically simple flow cytometry score described by the Ogata group for the diagnosis of myelodysplastic syndromes. A total of 652 patients were recruited prospectively in four different centers: 346 myelodysplastic syndromes, 53 myelodysplastic/myeloproliferative neoplasms, and 253 controls. The Ogata score was assessed using CD45 and CD34 staining, with the addition of CD10 and CD19. Moreover, labeling of CD5, CD7 and CD56 for the evaluation of myeloid progenitors and monocytes was tested on a subset of 294 patients. On the whole series, the specificity of Ogata score reached 89%. Respective sensitivities were 54% for low-risk myelodysplastic syndromes, 68% and 84% for type 1 and type 2 refractory anemia with excess of blasts, and 72% for myelodysplastic/myeloproliferative neoplasms. CD5 expression was poorly informative. When adding CD56 or CD7 labeling to the Ogata score, sensitivity rose to 66% for low-risk myelodysplastic syndromes, to 89% for myelodysplastic/myeloproliferative neoplasms and to 97% for refractory anemia with excess of blasts. This large multicenter study confirms the feasibility of Ogata scoring in routine flow cytometry diagnosis but highlights its poor sensitivity in low-risk myelodysplastic syndromes. The addition of CD7 and CD56 in flow cytometry panels improves the sensitivity but more sophisticated panels would be more informative.     

Tumour size over 3 cm predicts poor short-term outcomes after major liver resection for hilar cholangiocarcinoma. By the HC-AFC-2009 group

Introduction

As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection.

Methods

Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study''s objective was to identify pre-operative predictors of early death (<12 months) after a resection.

Results

The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24–85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136–7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038–10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis.

Conclusion

The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months.     

A systematic review and meta-analysis on the effects of crown lengthening on adjacent and non-adjacent sites

Clinical Oral Investigations - The objective of the study was to assess the impact of periodontal crown lengthening surgery on clinical parameters at adjacent and non-adjacent sites compared to...     

A new digital denture procedure: a first practitioners appraisal

Background

Historically, the complete removable denture is the last prosthetic procedure to switch to digital techniques whose advantages are mainly observed in the laboratory stages; however, it is not possible to measure the depressibility of the oral mucosa using optical cameras, thus conventional impression techniques are still necessary. This article describes the clinical and laboratory procedure and practitioners appraisal of the first fifteen digitally designed complete removable dental prostheses.

Methods

Several systems are now available including the Wieland® Digital Denture® which offers a complete procedure. This system is composed of a five axis-milling machine combined with a laboratory scanner and a design software application. Fifteen rehabilitations were carried out using the Wieland® system.

Results

The practitioner’s role is simplified by intraoral recording with a central point and a reduced number of sessions. The prosthesis laboratory requires considerable investment in learning and equipment, making it possible to obtain ideal mounting assemblies in accordance with the occluso-prosthetic concept of bilateral balanced occlusion. The absence of polymerization and therefore of base deformation risks reduce the equilibration step. Finally, the creation of templates as an alternative to the assembly of teeth on wax makes it possible to functionally validate (masticatory and phonatory) the future dentures. However, this procedure still presented some limitations in terms of scanning and software scope of applications.

Conclusion

Digital denture design software is relatively efficient and helps to standardize clinical results. However, to this date, improvements of the software are still required for a routine use.

     

Axonal Neuropathies due to Mutations in Small Heat Shock Proteins: Clinical,Genetic, and Functional Insights into Novel Mutations

In this study, we describe the phenotypic spectrum of distal hereditary motor neuropathy caused by mutations in the small heat shock proteins HSPB1 and HSPB8 and investigate the functional consequences of newly discovered variants. Among 510 unrelated patients with distal motor neuropathy, we identified mutations in HSPB1 (28 index patients/510; 5.5%) and HSPB8 (four index patients/510; 0.8%) genes. Patients have slowly progressive distal (100%) and proximal (13%) weakness in lower limbs (100%), mild lower limbs sensory involvement (31%), foot deformities (73%), progressive distal upper limb weakness (29%), mildly raised serum creatine kinase levels (100%), and central nervous system involvement (9%). We identified 12 HSPB1 and four HSPB8 mutations, including five and three not previously reported. Transmission was either dominant (78%), recessive (3%), or de novo (19%). Three missense mutations in HSPB1 (Pro7Ser, Gly53Asp, and Gln128Arg) cause hyperphosphorylation of neurofilaments, whereas the C‐terminal mutant Ser187Leu triggers protein aggregation. Two frameshift mutations (Leu58fs and Ala61fs) create a premature stop codon leading to proteasomal degradation. Two mutations in HSPB8 (Lys141Met/Asn) exhibited increased binding to Bag3. We demonstrate that HSPB1 and HSPB8 mutations are a major cause of inherited motor axonal neuropathy. Mutations lead to diverse functional outcomes further demonstrating the pleotropic character of small heat shock proteins.