The influence of developmental spinal stenosis on the risk of re-operation on an adjacent segment after decompression-only surgery for lumbar spinal stenosis.

AIMS: The aim of this study was to determine the influence of developmental spinal stenosis (DSS) on the risk of re-operation at an adjacent level. PATIENTS AND METHODS: This was a retrospective study of 235 consecutive patients who had undergone decompression-only surgery for lumbar spinal stenosis and had a minimum five-year follow-up. There were 106 female patients (45.1%) and 129 male patients (54.9%), with a mean age at surgery of 66.8 years (sd 11.3). We excluded those with adult deformity and spondylolisthesis. Presenting symptoms, levels operated on initially and at re-operation were studied. MRI measurements included the anteroposterior diameter of the bony spinal canal, the degree of disc degeneration, and the thickness of the ligamentum flavum. DSS was defined by comparative measurements of the bony spinal canal. Risk factors for re-operation at the adjacent level were determined and included in a multivariate stepwise logistic regression for prediction modelling. Odds ratios (ORs) with 95% confidence intervals were calculated. RESULTS: Of the 235 patients, 21.7% required re-operation at an adjacent segment. Re-operation at an adjacent segment was associated with DSS (p = 0.026), the number of levels decompressed (p = 0.008), and age at surgery (p = 0.013). Multivariate regression model (p < 0.001) controlled for other confounders showed that DSS was a significant predictor of re-operation at an adjacent segment, with an adjusted OR of 3.93. CONCLUSION: Patients with DSS who have undergone lumbar spinal decompression are 3.9 times more likely to undergo future surgery at an adjacent level. This is a poor prognostic indicator that can be identified prior to index decompression surgery.

Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy.

Acalabrutinib, a highly selective Bruton's tyrosine kinase inhibitor, is associated with high overall response rates and durable remission in previously treated chronic lymphocytic leukemia (CLL); however, complete remissions were limited. To elucidate on-target and pharmacodynamic effects of acalabrutinib, we evaluated several laboratory endpoints, including proteomic changes, chemokine modulation and impact on cell migration. Pharmacological profiling of samples from acalabrutinib-treated CLL patients was used to identify strategies for achieving deeper responses, and to identify additive/synergistic combination regimens. Peripheral blood samples from 21 patients with relapsed/refractory CLL in acalabrutinib phase I (100-400 mg/day) and II (100 mg BID) clinical trials were collected prior to and on days 8 and 28 after treatment initiation and evaluated for plasma chemokines, reverse phase protein array, immunoblotting and pseudoemperipolesis. The on-target pharmacodynamic profile of acalabrutinib in CLL lymphocytes was comparable to ibrutinib in measures of acalabrutinib-mediated changes in CCL3/CCL4 chemokine production, migration assays and changes in B-cell receptor signaling pathway proteins and other downstream survival proteins. Among several CLL-targeted agents, venetoclax, when combined with acalabrutinib, showed optimal complementary activity in vitro, ex vivo and in vivo in TCL-1 adoptive transfer mouse model system of CLL. These findings support selective targeting and combinatorial potential of acalabrutinib.

The use of the distal radius and ulna classification for the prediction of growth: peak growth spurt and growth cessation.

AIMS: We report the use of the distal radius and ulna (DRU) classification for the prediction of peak growth (PG) and growth cessation (GC) in 777 patients with idiopathic scoliosis. We compare this classification with other commonly used parameters of maturity. PATIENTS AND METHODS: The following data were extracted from the patients' records and radiographs: chronological age, body height (BH), arm span (AS), date of menarche, Risser sign, DRU grade and status of the phalangeal and metacarpal physes. The mean rates of growth were recorded according to each parameter of maturity. PG was defined as the summit of the curve and GC as the plateau in deceleration of growth. The rates of growth at PG and GC were used for analysis using receiver operating characteristic (ROC) curves to determine the strength and cutoff values of the parameters of growth. RESULTS: The most specific grades for PG using the DRU classification were radial grade 6 and ulnar grade 5, and for GC were radial grade 9 and ulnar grade 7. The DRU classification spanned both PG and GC, enabling better prediction of these clinically relevant stages than other methods. The rate of PG (≥ 0.7 cm/month) and GC (≤ 0.15 cm/month) was the same for girls and boys, in BH and AS measurements. CONCLUSION: This is the first study to note that the DRU classification can predict both PG and GC, providing evidence that it may aid the management of patients with idiopathic scoliosis. Cite this article: Bone Joint J 2016;98-B:1689-96.

N-acetyl-serotonin reduces copper (I) ion-induced lipid peroxidation in bovine retinal homogenates.

PURPOSE: Chalcosis is an ocular condition caused by penetration injury of copper or its alloy, which leads to extensive ocular inflammation. N-acetyl-serotonin has recently been identified as a potent antioxidant against free radical stress. In this study, we determined the efficacy of N-acetyl-serotonin against the copper (I)-induced retinal lipid peroxidation. METHODS: Copper (I)-treated (100 microM) bovine retinal homogenates were incubated with 6 different concentrations (i.e. 0.00, 0.25, 0.50, 1.00, 2.00 and 4.00 mM) of N-acetyl-serotonin or vitamin E. The malondialdehyde level was measured as an index of lipid peroxidation. RESULTS: Copper (I) ions induced a significant dose-dependent increase in malondialdehyde (p=0.007). Co-incubation with N-acetyl-serotonin or vitamin E significantly suppressed the copper (I)-induced malondialdehyde production (p<0.0001). The concentration to inhibit 50% of damage for N-acetyl-serotonin and vitamin E were found to be 1.54 mM and 0.45 mM, respectively. CONCLUSION: Although N-acetyl-serotonin is only 29% as effective as vitamin E in suppressing the copper (I)-induced lipid peroxidation, the present study supports a pharmacological potential of N-acetyl-serotonin combating free radical oxidative damages in the ocular tissues.