Characterization of Lumbar Lordosis: Influence of Age, Sex, Vertebral Body Wedging, and L4-S1.

STUDY DESIGN: Retrospective radiographic review. OBJECTIVE: The objectives of the study were to determine the contributions to lumbar lordosis (LL) through both the vertebrae and the intervertebral disc (IVD), and to investigate the relationships between lumbar sagittal spine measurements and age and gender. SUMMARY OF BACKGROUND DATA: A small body of literature exists on the relative contributions of vertebral body and IVD morphology to LL, the effects of L4-S1 on overall LL, and the relationships/correlations between lumbar sagittal spine measurements. METHODS: Patients who met the inclusion criteria were retrospectively evaluated. Measurements included LL, pelvic incidence (PI), and % contributions of vertebral body wedging/IVD wedging/L4-S1 to LL. Patients were separated into groups by age and sex, demographic data were collected, and statistical analysis was completed. RESULTS: LL decreased with age, although PI remained similar. Females demonstrated increased LL and vertebral body wedging % than males. Males demonstrated increased L4-S1% than females. Despite a decrease in LL with age, patients maintained L4-S1% and IVD wedging %. There was a significant negative relationship between PI and IVD wedging, PI and L4-S1%, and LL and L4-S1%. CONCLUSIONS: During aging, the lumbar spine loses LL linearly. This occurs in the IVD and vertebral bodies. Females have increased LL compared with males, because of an increase in vertebral body wedging and IVD/vertebral wedging cranial to L4. In patients with high PI or LL, increased LL occurs from cranial to L4 and from vertebral body wedging

Aldosterone and vasopressin affect α- and γ-ENaC mRNA translation

Vasopressin and aldosterone play key roles in the fine adjustment of sodium and water re-absorption in the nephron. The molecular target of this regulation is the epithelial sodium channel (ENaC) consisting of α-, β- and γ-subunits. We investigated mRNA-specific post-transcriptional mechanisms in hormone-dependent expression of ENaC subunits in mouse kidney cortical collecting duct cells. Transcription experiments and polysome gradient analysis demonstrate that both hormones act on transcription and translation. RNA-binding proteins (RBPs) and mRNA sequence motifs involved in translational control of γ-ENaC synthesis were studied. γ-ENaC–mRNA 3′-UTR contains an AU-rich element (ARE), which was shown by RNA affinity chromatography to interact with AU-rich element binding proteins (ARE-BP) like HuR, AUF1 and TTP. Some RBPs co-localized with γ-ENaC mRNA in polysomes in a hormone-dependent manner. Reporter gene co-expression experiments with luciferase γ-ENaC 3′-UTR constructs and ARE-BP expression plasmids demonstrate the importance of RNA–protein interaction for the up-regulation of γ-ENaC synthesis. We document that aldosterone and the V2 receptor agonist dDAVP act on synthesis of α- and γ-ENaC subunits mediated by RBPs as effectors of translation but not by mRNA stabilization. Immunoprecipitation and UV-crosslinking analysis of γ-ENaC–mRNA/HuR complexes document the significance of γ-ENaC–mRNA–3′-UTR/HuR interaction for hormonal control of ENaC synthesis

Knee Arthrofibrosis following Tibial Plateau Fracture Treated with Arthroscopic Lysis of Adhesions with Manipulation

AbstractPosttraumatic arthrofibrosis is a common problem encountered in the orthopaedic setting for which there is no agreement on the optimal management strategy. The literature does not optimally describe the efficacy of arthroscopic lysis of adhesions for arthrofibrosis following tibial plateau fracture. The purpose of this study is to quantify the efficacy of arthroscopic lysis of adhesions with manipulation for the treatment of arthrofibrosis of the knee in patients who previously underwent surgical management of tibial plateau fracture. All patients who underwent arthroscopic lysis of adhesions from a single surgeon since 1999 were retrospectively reviewed. Clinical outcomes were evaluated by flexion, extension, and range of motion (ROM) preoperatively, intraoperatively, and postoperatively at intervals of 1, 4, 8, and 12 weeks, and any additional long-term follow-up. A total of 28 patients who had developed arthrofibrosis following surgical management of a tibial plateau fracture and failed nonsurgical management of knee stiffness were included in this study. There were significant improvements in total ROM following intervention at all time points compared with preoperative values (p &lt; 0.001), with mean improvements of 59.3 degrees intraoperatively, 32.9 degrees (1 week), 37.1 degrees (4 weeks), 41.5 degrees (8 weeks), and 47.6 degrees (12 weeks). There were significant improvements in degrees of knee flexion following intervention at all time points compared with preoperative values (p &lt; 0.001), with mean improvements of 50.8 degrees intraoperatively, 27.3 degrees (1 week), 36.0 degrees (4 weeks), 38.3 degrees (8 weeks), and 43.9 degrees (12 weeks). There were significant increases in degrees of knee extension intraoperatively (8.5 degrees) and at 1 week postoperatively (5.9 degrees) compared with preoperative values (p &lt;0.01). At 12 weeks postoperatively, those who had previously undergone external fixation had significantly greater increases in ROM (p = 0.048). Arthroscopic lysis of adhesions for knee arthrofibrosis following surgical management of tibial plateau fracture significantly improves knee ROM.</jats:p

Phase (Ph) I/II study of pembrolizumab (P) with gemcitabine (G) in patients (pts) with previously-treated advanced (Adv) non-small cell lung cancer (NSCLC).

e20652 Background: P has demonstrated improved survival alone or with chemotherapy in untreated adv NSCLC. G may increase antigen cross-presentation and prime CD8 T cell response via tumor apoptosis. This study evaluated P + G in pts with previously-treated adv NSCLC naïve to anti-PD1. Methods: The study included ph 1 (previously reported), then single arm ph II, 1-3 prior therapies, regardless of PD-L1 status. Treatment: G, 1250 mg/m2, Days (D) 1 &amp; 8 + P 200 mg D 1; 21-day cycles. G given max 6 cycles, P max 2 years. Tumor tissue was collected for PD-L1 (22C3). Immune response via whole blood immunophenotyping and ProtoArray was conducted. Results: 16 pts enrolled. Male/Female: 8/8; Age 53-75 (Median 64.5); ECOG 0/1: 2/14 pts, respectively. Median prior therapies: 1 (Range (R) 1-3). Median cycles: 4 (R 1-24). Primary reason for discontinuation: progression. Toxicity was primarily attributed to G, including Gr 3: neutropenia (5), leukopenia (3), anemia (2); lymphopenia, URI, hyponatremia (1 each). Gr 4: 1 hypoxia attributed to intrapulmonary hemorrhage from G. Other toxicities attributed to both G and P included dyspnea (2), pneumonitis (2) (Gr 3). Progression free survival (PFS): 3.2 months (m) (R 0.6-18.5 m). Overall survival (OS) is not yet mature (4 pts in follow up). 14/16 pts were evaluable for response. Stable disease (SD): 9 (56%); partial response (PR): 2 (13%); progression (PD): 3 (19%). 2 pts discontinued prior to first evaluation (1 pulmonary hemorrhage; 1 clinical progression). 1 pt had SD as best response for 18.5 m before PD. Disease control rate (DCR; CR + PR + SD): 56%. 12 pts were PD-L1 evaluable (central). 2 pts had PD-L1 testing through alternate source (22C3). Of the 14 pts with PD-L1 result: PD-L1 0%: 8 (50%); PD-L1 10-40%: 3; ≥50%: 3 (19% each) PFS of 0% PD-L1: 3.75 m (1 PR, 6 SD; DCR 88%). PFS ≥50% PD-L1: 3 m (1 SD, 0 PR). Exploratory immune profiling showed late peripheral immune activation in 3 of 6 pts with Cycle 6 samples (all SD; PFS 5.8 m). ProtoArray analysis is pending. Conclusions: P+G was a feasible combination, without unexpected toxicity. The majority of pts had 0% PD-L1 expression. PFS was not associated with PD-L1 level. PFS did not differ from G or P alone. OS pending. Clinical trial information: NCT02422381. </jats:p