Effect of blue LED phototherapy centered at 478 nm versus 459 nm in hyperbilirubinemic neonates: a randomized study.

BACKGROUND: Treatment of choice for hyperbilirubinemic neonates is blue light matching the absorption spectrum of bilirubin-albumin in vitro with maximum absorption at 459 nm. Blue LED light centered at 478 nm was hypothesized as being more efficient than that centered at 459 nm. This study compares the bilirubin-reducing effect of the two light qualities with equal irradiance in a randomized nonblinded clinical trial. METHODS: Inclusion criteria were healthy hyperbilirubinemic neonates with gestational age ≥33 weeks. Forty-nine neonates included in each group received phototherapy from above for 24 h. Mean irradiances were 9.2 × 1015 and 9.0 × 1015 photons/cm2/s for the 478 and 459 nm groups, respectively. RESULTS: Mean [95% CI] decreases in total serum bilirubin were 150 [141, 158] and 120 [111, 130] µmol/L for the 478 and 459 nm groups, respectively; mean difference was 29 [17, 42] µmol/L. Mean [95% CI] percentage decreases in bilirubin were 54.8% [52.5, 57.0] and 41.8% [39.3, 44.3]; mean difference was 12.9 [9.6, 16.3] percentage points. After adjustment this difference was 13.4 [10.2, 16.7] percentage points. All differences were highly statistically significant (P < 0.001). CONCLUSION: Blue LED light centered at 478 nm had a greater bilirubin-reducing effect than that centered at 459 nm with equal irradiance quantified as photon fluence rate. IMPACT: Blue LED light centered at 478 nm had a greater in vivo bilirubin-reducing effect than blue LED light centered at 459 nm with equal irradiance quantified as photon fluence rate in the treatment of hyperbilirubinemic late preterm or term neonates. LED light centered at 478 nm might reduce the duration of phototherapy compared to LED light centered at 459 nm as the same effect can be obtained while exposing the infants to fewer photons. Blue light matching the absorption spectrum of the bilirubin-albumin complex in vitro with peak absorption at 459 nm is used worldwide as it is considered to be the most effective light for phototherapy of jaundiced neonates. This study showed that blue LED light centered at 478 nm had a greater bilirubin-reducing effect than blue LED light centered at 459 nm. Therefore, blue LED light centered at 478 nm should be used instead of blue light centered at 459 nm. By this, the risk of potential side effects might be minimized, and the duration of phototherapy potentially reduced.

Interactions between SNPs affecting inflammatory response genes are associated with multiple myeloma disease risk and survival.

The origin of multiple myeloma depends on interactions with stromal cells in the course of normal B-cell differentiation and evolution of immunity. The concept of the present study is that genes involved in MM pathogenesis, such as immune response genes, can be identified by screening for single-nucleotide polymorphisms (SNPs) involved in the immune response and a subsequent statistical analysis that focusses on the association of SNPs, certain haplotypes or SNP-SNP interactions with MM risk and prognosis. We genotyped 348 Danish patients and 355 controls for 13 SNPs located in the TNFA, IL-4, IL-6, IL-10 and CHI3L1 gene promoters. The occurrence of single polymorphisms, haplotypes and SNP-SNP interactions were statistically analyzed for association with disease risk and outcome following high-dose therapy. Identified genes that carried SNPs or haplotypes that were identified as risk or prognostic factors were studied for expression in normal B-cell subsets and myeloma plasma cells. We observed a significantly reduced risk when harboring the TNFA-238A allele (OR = 0.51 (0.29-0.86)) and interactions between the TNFA-1031T/C * and IL-10 -3575T/A (p = .007) as well as the TNFA-308G/A * and IL-10-1082G/A (p = .008) allels. By statistical approaches, we observed association between prognosis and the TNFA-857CC genotype (HR = 2.80 (1.29-6.10)) and IL-10-1082GG + GA genotypes (HR = 1.93 (1.07-3.49)) and interactions between IL-6-174G/C and IL-10-3575T/A (p = .001) and between TNFA-308G/A and IL-4-1098T/G (p= .005). The 'risk genes' were analyzed for expression in normal B-cell subsets (N = 6) from seven healthy donors and we found TNFA and IL-6 expressed both in naïve and in memory B cells when compared to preBI, II, immature and plasma cells. The 'prognosis genes' CHI3L1, IL-6 and IL-10 were differential expressed in malignant plasma cells when comparing poor and good prognosis groups based on to the TC classification. In summary, these findings suggest that TNFA, IL-4, IL-6, IL-10 and CHI3L1 might be important players in MM pathogenesis during disease initiation and drug resistance in multiple myeloma.

Surgically assisted rapid maxillary expansion (SARME) with or without intraoperative releasing of the nasal septum.

OBJECTIVE: To assess nasal septum deviation after surgically assisted rapid maxillary expansion (SARME) with or without intraoperative releasing of the nasal septum. STUDY DESIGN: A total of 20 consecutive adult patients with transverse maxillary deficiency underwent SARME with intraoperative releasing (n = 10) or nonreleasing (n = 10) of the nasal septum. Cone beam computed tomography scans were obtained immediately after surgery (T1), after the end of distraction (T2), and 6 months after SARME (T3). Deviation of the nasal septum was evaluated by angular measurements on superimposed cone beam computed tomography images from T1 to T3. Moreover, visible nasal septum deviation was assessed by using superimposed clinical photos obtained preoperatively (CP1) and before second-stage surgery (CP2). RESULTS: No significant differences were found between releasing and nonreleasing of the nasal septum in angular radiographic measurements from T1 to T3 (0 degrees; 95% confidence interval -0.62 to 0.62; P = .5) or visible nasal deviation from CP1 to CP2 (-0.14 degrees; 95% confidence interval -0.64 to 0.36; P = .28). CONCLUSIONS: The results of the present study indicate that there is no need for intraoperative releasing of the nasal septum during SARME. However, further randomized studies based on large patient groups are needed before final conclusions on this topic can be reached.

Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation.

OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHODS: A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric radiographs obtained preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively (T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the mandibular plane angle (MP-angle) was used to determine the vertical facial type. RESULTS: The mean advancement from T1 to T2 were 11.6 mm and 13.5 mm at B-point and Pog, respectively. The mean skeletal relapse from T2 to T3 was -1.3 mm at B-point and -1.6 mm at Pog. The nineteen patients characterized as long facial types, showed the highest amount of skeletal relapse (-1.5 mm at B-point and -1.9 mm at Pog). CONCLUSIONS: The present study showed a limited amount of skeletal relapse in large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation. Bilateral sagittal split osteotomy in combination with skeletal intermaxillary fixation can therefore be an alternative to distraction osteogenesis in large mandibular advancements.

Inherited Inflammatory Response Genes Are Associated with B-Cell Non-Hodgkin's Lymphoma Risk and Survival.

BACKGROUND: Malignant B-cell clones are affected by both acquired genetic alterations and by inherited genetic variations changing the inflammatory tumour microenvironment. METHODS: We investigated 50 inflammatory response gene polymorphisms in 355 B-cell non-Hodgkin's lymphoma (B-NHL) samples encompassing 216 diffuse large B cell lymphoma (DLBCL) and 139 follicular lymphoma (FL) and 307 controls. The effect of single genes and haplotypes were investigated and gene-expression analysis was applied for selected genes. Since interaction between risk genes can have a large impact on phenotype, two-way gene-gene interaction analysis was included. RESULTS: We found inherited SNPs in genes critical for inflammatory pathways; TLR9, IL4, TAP2, IL2RA, FCGR2A, TNFA, IL10RB, GALNT12, IL12A and IL1B were significantly associated with disease risk and SELE, IL1RN, TNFA, TAP2, MBL2, IL5, CX3CR1, CHI3L1 and IL12A were, associated with overall survival (OS) in specific diagnostic entities of B-NHL. We discovered noteworthy interactions between DLBCL risk alleles on IL10 and IL4RA and FL risk alleles on IL4RA and IL4. In relation to OS, a highly significant interaction was observed in DLBCL for IL4RA (rs1805010) * IL10 (rs1800890) (HR = 0.11 (0.02-0.50)). Finally, we explored the expression of risk genes from the gene-gene interaction analysis in normal B-cell subtypes showing a different expression of IL4RA, IL10, IL10RB genes supporting a pathogenetic effect of these interactions in the germinal center. CONCLUSIONS: The present findings support the importance of inflammatory genes in B-cell lymphomas. We found association between polymorphic sites in inflammatory response genes and risk as well as outcome in B-NHL and suggest an effect of gene-gene interactions during the stepwise oncogenesis.

Periodontal changes after surgically assisted rapid maxillary expansion (SARME).

PURPOSE: The objective of the present study was to evaluate the health status of the periodontal tissue after surgically assisted rapid maxillary expansion (SARME). METHODS: Periodontal status was assessed after an average of 25 months (range, 6-66) in 61 patients who underwent SARME by plaque index, gingival index, probing depth, and probing attachment level. In the maxilla, six measurements were made at the central incisor, second premolar, and first molar. Corresponding measurements were made in the mandible as control. The measurements were estimated and expressed with 95 % confidence interval (CI). Additionally, maxillary occlusal radiographs of the maxillary central incisors were evaluated for signs of root resorption. RESULTS: There was no statistically significant difference between experimental and control teeth with respect to plaque index, probing depth, or attachment level. The gingival index of the maxillary central incisor was significantly higher compared to control (CI 0.175 (0.09-0.26), p value p < 0.001). External apical root resorption of the anterior maxillary teeth was observed in 36 % of the patients. CONCLUSIONS: Within the limitations of a retrospective study, the present study seems to demonstrate that SARME does not affect the health status of the periodontal tissues. However, further randomized long-term studies are needed before final conclusions can be provided.

Diffuse large B-cell lymphoma classification system that associates normal B-cell subset phenotypes with prognosis.

PURPOSE: Current diagnostic tests for diffuse large B-cell lymphoma use the updated WHO criteria based on biologic, morphologic, and clinical heterogeneity. We propose a refined classification system based on subset-specific B-cell-associated gene signatures (BAGS) in the normal B-cell hierarchy, hypothesizing that it can provide new biologic insight and diagnostic and prognostic value. PATIENTS AND METHODS: We combined fluorescence-activated cell sorting, gene expression profiling, and statistical modeling to generate BAGS for naive, centrocyte, centroblast, memory, and plasmablast B cells from normal human tonsils. The impact of BAGS-assigned subtyping was analyzed using five clinical cohorts (treated with cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP], n = 270; treated with rituximab plus CHOP [R-CHOP], n = 869) gathered across geographic regions, time eras, and sampling methods. The analysis estimated subtype frequencies and drug-specific resistance and included a prognostic meta-analysis of patients treated with first-line R-CHOP therapy. RESULTS: Similar BAGS subtype frequencies were assigned across 1,139 samples from five different cohorts. Among R-CHOP-treated patients, BAGS assignment was significantly associated with overall survival and progression-free survival within the germinal center B-cell-like subclass; the centrocyte subtype had a superior prognosis compared with the centroblast subtype. In agreement with the observed therapeutic outcome, centrocyte subtypes were estimated as being less resistant than the centroblast subtype to doxorubicin and vincristine. The centroblast subtype had a complex genotype, whereas the centrocyte subtype had high TP53 mutation and insertion/deletion frequencies and expressed LMO2, CD58, and stromal-1-signature and major histocompatibility complex class II-signature genes, which are known to have a positive impact on prognosis. CONCLUSION: Further development of a diagnostic platform using BAGS-assigned subtypes may allow pathogenetic studies to improve disease management.

A model system for assessing and comparing the ability of exon microarray and tag sequencing to detect genes specific for malignant B-cells.

BACKGROUND: Malignant cells in tumours of B-cell origin account for 0.1% to 98% of the total cell content, depending on disease entity. Recently, gene expression profiles (GEPs) of B-cell lymphomas based on microarray technologies have contributed significantly to improved sub-classification and diagnostics. However, the varying degrees of malignant B-cell frequencies in analysed samples influence the interpretation of the GEPs. Based on emerging next-generation sequencing technologies (NGS) like tag sequencing (tag-seq) for GEP, it is expected that the detection of mRNA transcripts from malignant B-cells can be supplemented. This study provides a quantitative assessment and comparison of the ability of microarrays and tag-seq to detect mRNA transcripts from malignant B-cells. A model system was established by eight serial dilutions of the malignant B-cell lymphoma cell line, OCI-Ly8, into the embryonic kidney cell line, HEK293, prior to parallel analysis by exon microarrays and tag-seq. RESULTS: We identified 123 and 117 differentially expressed genes between pure OCI-Ly8 and HEK293 cells by exon microarray and tag-seq, respectively. There were thirty genes in common, and of those, most were B-cell specific. Hierarchical clustering from all dilutions based on the differentially expressed genes showed that neither technology could distinguish between samples with less than 1% malignant B-cells from non-B-cells. A novel statistical concept was developed to assess the ability to detect single genes for both technologies, and used to demonstrate an inverse proportional relationship with the sample purity. Of the 30 common genes, the detection capability of a representative set of three B-cell specific genes--CD74, HLA-DRA, and BCL6 - was analysed. It was noticed that at least 5%, 13% and 22% sample purity respectively was required for detection of the three genes by exon microarray whereas at least 2%, 4% and 51% percent sample purity of malignant B-cells were required for tag-seq detection. CONCLUSION: A sample purity-dependent loss of the ability to detect genes for both technologies was demonstrated. Taq-seq, in comparison to exon microarray, required slightly less malignant B-cells in the samples analysed in order to detect the two most abundantly expressed of the selected genes. The results show that malignant cell frequency is an important variable, with fundamental impact when interpreting GEPs from both technologies.