Biomechanical Comparison of Posterior Fixation Using Spinal Instrumentation and Conventional Posterior Plate Fixation in Unstable Vertical Sacral Fracture

Vertical sacral fracture is one of the most difficult fractures to treat. Posterior fixation using spinal dual rods is a novel method for treating this fracture, but its biomechanical strength has not yet been reported. The aim of this study was to evaluate the biomechanical strength produced by posterior fixation using spinal instrumentation. Sacral fractures were created in eight pelvic bone models and classified into a posterior plate fixation group [P group, n＝4] and a spinal instrumentation group [R group, n＝4]. The biomechanical strength was tested by pushing down on the S1 vertebra from the top. The mean maximum loads were 1,057.4 N and 1,489.4 N in the P and R groups, respectively (p＝0.014). The loads applied to the construct at displacements of 5mm and 7.5mm from the start of the universal testing machine loading were also significantly higher in the R group. The mean stiffness levels in the P and R groups were 88.3N/mm and 119.6N/mm, respectively (p＝0.014). Posterior fixation using spinal instrumentation is biomechanically stronger than conventional posterior plate fixation. This procedure may be the optimal method for treating unstable sacral fracture fixation

Impact of a New Medical Record System for Emergency Departments Designed to Accelerate Clinical Documentation: A Crossover Study.

Recording information in emergency departments (EDs) constitutes a major obstacle to efficient treatment. A new electronic medical records (EMR) system focusing on clinical documentation was developed to accelerate patient flow. The aim of this study was to examine the impact of a new EMR system on ED length of stay and physician satisfaction.We integrated a new EMR system at a hospital already using a standard system. A crossover design was adopted whereby residents were randomized into 2 groups. Group A used the existing EMR system first, followed by the newly developed system, for 2 weeks each. Group B followed the opposite sequence. The time required to provide overall medical care, length of stay in ED, and degree of physician satisfaction were compared between the 2 EMR systems.The study involved 6 residents and 526 patients (277 assessed using the standard system and 249 assessed with the new system). Mean time for clinical documentation decreased from 133.7 ± 5.1 minutes to 107.5 ± 5.4 minutes with the new EMR system (P < 0.001). The time for overall medical care was significantly reduced in all patient groups except triage level 5 (nonurgent). The new EMR system significantly reduced the length of stay in ED for triage level 2 (emergency) patients (145.4 ± 13.6 minutes vs 184.3 ± 13.6 minutes for standard system; P = 0.047). As for the degree of physician satisfaction, there was a high degree of satisfaction in terms of the physical findings support system and the ability to capture images and enter negative findings.The new EMR system shortened the time for overall medical care and was associated with a high degree of resident satisfaction

Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker

Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity

Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non‑small cell lung cancer

Purpose: Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer. Patients and methods: We retrospectively reviewed all patients diagnosed with advanced or metastatic non-small cell lung cancer (NSCLC) and treated with ICI monotherapy (nivolumab, pembrolizumab, and atezolizumab) between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Early death was defined as patients who died within 60 days of ICI treatment. Results: A total of 166 patients were included. The majority of patients (87%) had an Eastern cooperative oncology group (ECOG) Performance status (PS) of 0/1. There were 21 early deaths. Significant differences were observed in ECOG PS, the histological type, liver metastasis, tumor size, the white blood cell count, neutrophils (%), lymphocytes (%), the neutrophilto-lymphocyte ratio in serum (sNLR), C-reactive protein (CRP), and albumin between the groups with or without early death. Univariate logistic regression analyses identified ECOG PS score ≥ 2, liver metastasis, tumor size ≥ 5 cm, neutrophils ≥ 69%, lymphocytes < 22%, sNLR ≥ 4, CRP ≥ 1 mg/dl, and albumin < 3.58 g/dl as significant risk factors for early death. A multivariate logistic regression analysis revealed that liver metastasis (Odds ratio [OR], 10.3; p = 0.008), ECOG PS score ≥ 2 (OR, 8.0; p = 0.007), and a smoking history (OR, 0.1; p = 0.03) were significant risk factors for early death. Conclusion: Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC

Dok-1 and Dok-2 are negative regulators of lipopolysaccharide-induced signaling

Endotoxin, a bacterial lipopolysaccharide (LPS), causes fatal septic shock via Toll-like receptor (TLR)4 on effector cells of innate immunity like macrophages, where it activates nuclear factor κB (NF-κB) and mitogen-activated protein (MAP) kinases to induce proinflammatory cytokines such as tumor necrosis factor (TNF)-α. Dok-1 and Dok-2 are adaptor proteins that negatively regulate Ras–Erk signaling downstream of protein tyrosine kinases (PTKs). Here, we demonstrate that LPS rapidly induced the tyrosine phosphorylation and adaptor function of these proteins. The stimulation with LPS of macrophages from mice lacking Dok-1 or Dok-2 induced elevated Erk activation, but not the other MAP kinases or NF-κB, resulting in hyperproduction of TNF-α and nitric oxide. Furthermore, the mutant mice showed hyperproduction of TNF-α and hypersensitivity to LPS. However, macrophages from these mutant mice reacted normally to other pathogenic molecules, CpG oligodeoxynucleotides, poly(I:C) ribonucleotides, or Pam3CSK4 lipopeptide, which activated cognate TLRs but induced no tyrosine phosphorylation of Dok-1 or Dok-2. Forced expression of either adaptor, but not a mutant having a Tyr/Phe substitution, in macrophages inhibited LPS-induced Erk activation and TNF-α production. Thus, Dok-1 and Dok-2 are essential negative regulators downstream of TLR4, implying a novel PTK-dependent pathway in innate immunity

A Note on Randomized Algorithm for String Matching with Mismatches

Atallah et al. [ACD01] introduced a randomized algorithm for string matching with mismatches, which utilized fast Fourier transformation (FFT) to compute convolution. It estimates the score vector of matches between text string and a pattern string, i.e. the vector obtained when the pattern is slid along the text, and the number of matches is counted for each position. In this paper, we simplify the algorithm and give an exact analysis of the variance of the estimator. Key words: Pattern matching, mismatch, FFT, convolution, randomized algorithm