Endonasal flap suture-dacryocystorhinostomy (eFS-DCR): a new surgical technique for nasolacrimal duct obstruction (NLDO)

Conclusion: Endonasal flap suture-dacryocystorhinostomy (eFS- DCR) is a new and valuable technique for the treatment of nasolacrimal duct obstruction (NLDO). This technique could improve the success rate of endonasal DCR in comparison to external DCR. Objective: The standard procedure for NLDO is DCR. DCR can be performed via either an external or endonasal approach. External DCR is now regarded as the gold standard in the treatment of NLDO because of its higher success rate. However, we report a new endonasal surgical technique, eFS-DCR, and assess its efficacy by comparison with the standard endonasal DCR. Methods: We prospectively investigated a series of 62 consecutive patients with NLDO undergoing endonasal DCR. There were two surgical intervention groups: group 1 (24 patients, 28 sites) undergoing endonasal DCR without eFS; and group 2 (38 patients, 47 sites) undergoing eFS-DCR. Study end points were success rate, the ostium diameter (OD) of the lacrimal sac after DCR, and the duration of stent placement. We compared the two groups on these three points. Results: The success rate was 78.6% (22 of 28 sites) for group 1 (DCR without eFS) and 97.9% (46 of 47 sites) for group 2 (eFS-DCR). The ostium size in patients in group 2 was larger than that in group 1. The median time for the duration of stent placement was 42.5 days for group 1 and 31.5 days for group 2. There was a statistical difference (p < 0.01) in all these parameters between the two groups.     

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86–90) versus 92% (90–94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54–59) versus 87% (85–90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992–1999 versus 2000–2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia.     

High-dose 131I-metaiodobenzylguanidine therapy in patients with high-risk neuroblastoma in Japan

Annals of Nuclear Medicine - The aim of the study was to investigate the outcomes and prognostic factors of high-dose 131I-metaiodobenzylguanidine (131I-MIBG) therapy in patients with refractory or...     

Solution-phase synthesis of oligodeoxyribonucleotides using the H-phosphonate method with N-unprotected 5′-phosphite monomers

Recent advances in nucleic acid therapeutics increase the requirements for developing efficient methods for the chemical synthesis of oligodeoxyribonucleotides (ODNs). In this study, we report a new approach for the solution-phase synthesis of ODNs using the H-phosphonate method with N-unprotected 5′-phosphite monomers. The 5′-phosphite monomers are synthesized in a single step from unprotected 2′-deoxyribonucleosides using 5′-O-selective phosphitylation and can be applied to the synthetic cycle of the H-phosphonate method. We synthesized four kinds of 5′-phosphite monomers and then optimized the conditions for the condensation between the 3′-hydroxy groups of the 5′-phosphite monomers and the H-phosphonate monoesters. As a result of various investigations, solution-phase synthesis of trithymidine diphosphate (TTT) and tetramers containing four kinds of nucleobases was achieved according to the procedure consisting of repeated condensation, deprotection, and purification using simple extraction or precipitation.

A new strategy for a solution-phase synthesis of oligodeoxyribonucleotides with 5′-phosphite monomers synthesized in a single step from unprotected 2′-deoxyribonucleosides.     

Utility of a Score for Predicting Glomerular Filtration Rate Overestimation in Patients with Cardiovascular and Renal Diseases and Their Risk Factors

Objective We recently reported a novel score for the detection of glomerular filtration rate (GFR) overestimation using a creatinine-based equation. We examined the utility of this score in patients with cardiovascular/renal diseases and diabetes mellitus. Methods We enrolled 1,425 patients (65±15 years old; 37% women) who were admitted to our hospital for the management of cardiovascular and renal diseases and their risk factors. Overestimation of the GFR (OE) was defined as a creatinine-based GFR (eGFRcre) ≥120% of the cystatin C-based estimated GFR. The OE score was calculated as the sum of the scores for the body weight, hemoglobin concentration, and blood urea nitrogen (BUN)/serum creatinine (Scr), totaling 1 point if the body weight was <63.0 kg in men or <42.0 kg in women, 1 point if the hemoglobin concentration was <12.4 g/dL in men or <11.0 g/dL in women, and 1 point if the BUN/Scr was >26.5. Results The proportion of patients with OE was 14.2%. The score predicted OE with a sensitivity of 70.8% and a specificity of 99.6%, and the sensitivity was increased in patients ≥75 years old (88.3%) and decreased in diabetics (58.6%). When patients were divided into subgroups by the total score, the frequencies of OE were 8% (59/754), 14% (72/502), 38% (58/151), and 72% (13/18) in patients with scores of 0, 1, 2, and 3, respectively. Conclusion The OE score is useful for detecting elderly cases of cardiovascular and renal diseases in which eGFRcre overestimates the GFR, although its utility is limited in diabetics.     

YES1 activation induces acquired resistance to neratinib in HER2‐amplified breast and lung cancers

Molecular‐targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan‐HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2‐positive breast cancer. However, acquired resistance of various cancers to molecular‐targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib‐resistant cell lines from HER2‐amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib‐resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1‐amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2‐targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome.