A culture method with berbamine, a plant alkaloid, enhances CAR-T cell efficacy through modulating cellular metabolism.

Memory T cells demonstrate superior in vivo persistence and antitumor efficacy. However, methods for manufacturing less differentiated T cells are not yet well-established. Here, we show that producing chimeric antigen receptor (CAR)-T cells using berbamine (BBM), a natural compound found in the Chinese herbal medicine Berberis amurensis, enhances the antitumor efficacy of CAR-T cells. BBM is identified through cell-based screening of chemical compounds using induced pluripotent stem cell-derived T cells, leading to improved viability with a memory T cell phenotype. Transcriptomics and metabolomics using stem cell memory T cells reveal that BBM broadly enhances lipid metabolism. Furthermore, the addition of BBM downregulates the phosphorylation of p38 mitogen-activated protein kinase and enhanced mitochondrial respiration. CD19-CAR-T cells cultured with BBM also extend the survival of leukaemia mouse models due to their superior in vivo persistence. This technology offers a straightforward approach to enhancing the antitumor efficacy of CAR-T cells.

Estimation of the rupture point of the craniovertebral junction intradural arteriovenous fistula with vessel wall magnetic resonance image and its pathological findings: A case report.

Background: Arteriovenous fistulas (AVFs) of the craniocervical junction (CCJ) and intradural AVFs are often associated with aneurysms and varics, and it is sometimes difficult to identify the ruptured point on radiological images. We report a case in which vessel wall magnetic resonance image (VW-MRI) was useful for identifying the ruptured point at the CCJ AVF. Case Description: A 70-year-old man presented with a sudden onset of headache. He had Glasgow Coma Scale E4V5M6, world federation of neurosurgical societies (WFNS) Grade I. Fisher group 3 subarachnoid hemorrhage and hydrocephalus were found on head computed tomography. Cerebral angiography showed a spinal AVF at the C1 level of the cervical spine. Magnetic resonance image-enhanced motion sensitized driven equilibrium (MSDE-method showed an enhancing effect in part of the AVF draining vein, but the vascular architecture of this lesion was indeterminate. We performed continuous ventricular drainage for acute hydrocephalus and antihypertensive treatment. Cerebral angiography was performed 30days after the onset of the disease, and was revealed an aneurysmal structure in a portion of the AVF draining vein, which VW-MRI initially enhanced. On the 38th day after onset, he underwent direct surgery to occlude the AV fistula and dissect the aneurysmal structure. Histopathology showed that the aneurysmal structure was varices with lymphocytic infiltration, and hemosiderin deposition was observed near the varices. Conclusion: Recently, VW-MRI has been reported to show an association between the enhancement of varices in dural AVF and rupture cases. VW-MRI, especially the enhanced MSDE method, may be useful in estimating the ruptured point in arteriovenous shunt disease.

Effective and stable gene transduction in rhesus macaque iPSCs capable of T-lineage differentiation utilizing the piggyBac system.

Introduction: Genetically modified human induced pluripotent stem cell (iPSC)-based regenerative medicine has substantial potential in the treatment of refractory human diseases. Thus, preclinical studies on the safety and efficacy of these products are essential. Non-human primate (NHP) models such as the rhesus macaque are highly similar to humans in terms of size, lifespan, and immune system, rendering them superior models. However, effective gene transduction in rhesus macaque iPSCs (Rh-iPSCs) remains challenging. In this study, we investigated the effective gene transduction into Rh-iPSCs and its effect on differentiation efficiency. Methods: We established a gene transduction method using the piggyBac transposon vector system. Gene transduced Rh-iPSCs were analyzed for undifferentiated markers. We did teratoma assay to check pluripotency. Gene transduced Rh-iPSCs were differentiated into hematopoietic stem and progenitor cells (HSPCs) and T-cell lineage cells. Additionally, gene transduced Rh-iPSCs were compared the differentiation efficiency with parental Rh-iPSCs. Results: We could establish a gene transduction method using the piggyBac transposon vector system, demonstrating high efficiency and stable transgene expression in Rh-iPSCs. These Rh-iPSCs maintained long-term gene expression while expressing undifferentiated markers. Teratoma assay indicated that these Rh-iPSCs had pluripotency. These Rh-iPSCs could differentiate into HPSCs and T cells that express transgenes. These Rh-iPSCs can differentiate into hematopoietic stem cells and T cells that express transgenes. No significant differences in efficiency of differentiation were observed between parental Rh-iPSCs and these Rh-iPSCs. Conclusions: These results indicate that the piggyBac transposon vector is an excellent gene transfer tool for rhesus macaque iPSCs and could contribute to the advancement of preclinical studies using rhesus macaque iPSCs.

Late-onset aqueductal membranous occlusion treated neuroendoscopic procedure and consideration of its pathological findings: A case report.

Background: Aqueduct of Sylvius stenosis/obstruction interferes with cerebrospinal fluid (CSF) flow and leads to the non-communicating hydrocephalus. Acquired non-neoplastic causes of aqueduct of Sylvius stenosis/ obstruction include simple stenosis, gliosis, slit-like stenosis, and septal formation, but the detailed mechanisms are not clear. In the present study, we experienced a case of late-onset aqueductal membranous occlusion (LAMO) successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structures of the aqueduct of Sylvius occlusion. Case Description: A 66-year-old woman presented with gradually progressive gait disturbance, cognitive dysfunction, and urinary incontinenc. Brain magnetic resonance imaging (MRI) showed enlargement of the bilateral lateral ventricles and the third ventricle without dilatation of fourth ventricle, and heavily T2-weighted images showed an enlarged aqueduct of Sylvius and a membranous structure at its caudal end. Gadolinium contrast-enhanced T1-weighted images showed no neoplastic lesions. We diagnosed this case that the hydrocephalus due to late-onset idiopathic aqueductal stenosis or LAMO and the patient underwent endoscopic third ventriculostomy and endoscopic aqueduct oplasty. Membranous tissue specimens were obtained from the occluded aqueduct of Sylvius at the time of treatment. Histopathological examination revealed gliosis, and inside the gliosis, there were cell clusters that appeared to be ependymal cells and were corpora amylacea. We confirmed CSF flow at the site of obstruction of the aqueduct of Sylvius and the stoma of the third ventricle floor by MRI images. Her symptoms were improved immediately. Conclusion: We experienced a case of LAMO successfully treated by neuroendoscopic procedure, which allowed us to examine the pathology of the membranous structure of the aqueduct of Sylvius. The pathological study of LAMO is rare, and we report it, including a review of the literature.

Optimal threshold of a control parameter for tomotherapy respiratory tracking: A phantom study.

BACKGROUND: Radixact Synchrony® , a real-time motion tracking and compensating modality, is used for helical tomotherapy. Control parameters are used for the accurate application of irradiation. Radixact Synchrony® uses the potential difference, which is an index of the accuracy of the prediction model of target motion and is represented by a statistical prediction of the 3D distance error. Although there are several reports on Radixact Synchrony® , few have reported the appropriate settings of the potential difference threshold. PURPOSE: This study aims to determine the optimal threshold of the potential difference of Radixact Synchrony® during respiratory tumor-motion-tracking irradiation. METHODS: The relationship among the dosimetric accuracy, motion tracking accuracy, and control parameter was evaluated using a moving platform, a phantom with a basic respiratory model (the fourth power of a sinusoidal wave), and several irregular respiratory model waveforms. The dosimetric accuracy was evaluated by gamma analysis (3%, 1 mm, 10% dose threshold). The tracking accuracy was measured by the distance error of the difference between the tracked and driven positions of the phantom. The largest potential difference for 95% of treatment time was evaluated, and its correlation with the gamma-pass ratio and distance error was investigated. The optimal threshold of the potential difference was determined by receiver operating characteristic (ROC) analysis. RESULTS: A linear correlation was identified between the potential difference and the gamma-pass ratio (R = -0.704). A linear correlation was also identified between the potential difference and distance error (R = 0.827). However, as the potential difference increased, it tended to underestimate the distance error. The ROC analysis revealed that the appropriate cutoff value of the potential difference was 3.05 mm. CONCLUSION: The irradiation accuracy with motion tracking by Radixact Synchrony® could be predicted from the potential difference, and the threshold of the potential difference should be set to ∼3 mm.

Low Radiation Protocol for Intraoperative Robotic C-Arm Can Enhance Adolescent Idiopathic Scoliosis Deformity Correction Accuracy and Safety.

STUDY DESIGN: Retrospective case-series study. OBJECTIVES: To assess (1) low cone beam CT (CBCT) mediated intraoperative navigation to limit radiation exposure without compromising surgical accuracy, and (2) the potential of intraoperative C-arm CBCT navigation to augment pedicle screw (PS) placement accuracy in AIS surgery compared to pre-surgery CT-based planning. METHODS: The first part involved a prospective phantom study, comparing radiation doses for conventional CT, and standard (6sDCT) and a low dose (5sDCT) Artis Zeego®-imaging. Next, 5sDCT- and 6sDCT-navigation were compared on PS accuracy and radiation exposure during AIS correction. The final part compared surgical AIS deformity correction through intraoperative 5sDCT navigation to a matched cohort treated using conventional pre-surgery CT-scans for navigation. Outcome parameters included operation time, skin dose (SD), dose area product (DAP), intraoperative blood loss, postoperative complications, and PS deviation rates. RESULTS: The phantom study demonstrated a reduction in radiation for the 5sDCT protocol. Moreover, 5sDCT-imaged patients (n = 15) showed a significantly lower SD (-27.41%) and DAP (-30.92%), without compromising PS accuracy compared with 6sDCT-settings (n = 15). Finally, AIS correction through intraoperative CBCT C-arm navigation (n = 27) significantly reduced screw deviation rates (6.83% versus 10.75%, P = .016) without increasing operation times, compared with conventional CT (n = 37). CONCLUSIONS: Intraoperative navigation using a CBCT C-arm system improved the accuracy of PS insertion and reduced surgery time. Moreover, it reduced radiation exposure compared with conventional CT, which was further curtailed by adapting the low-dose 5sDCT protocol. In short, our study highlights the benefits of intraoperative CBCT navigation for PS placement in AIS surgery.

First-line pembrolizumab for patients with early relapsing urothelial carcinoma after perioperative chemotherapy: a retrospective analysis of bladder cancer and upper urinary tract cancer.

BACKGROUND: First-line pembrolizumab is available for recurrent disease within 12 months after the receipt of platinum-based perioperative chemotherapy. However, the benefit of first-line pembrolizumab is unclear. This study evaluated the oncological outcome of patients treated with pembrolizumab compared with chemotherapy as first-line therapy for early relapsing disease after the receipt of platinum-based perioperative chemotherapy. METHODS: Data from a multicenter study included 454 patients diagnosed with unresectable or metastatic UC from November 2006 to July 2021. We identified patients with early and non-early relapsing disease. Oncological outcomes were evaluated using progression-free survival, overall survival, and survival with disease control. RESULTS: Fifty-three patients with early relapsing disease and 15 patients with non-early relapsing disease were identified. Of 53 patients with early relapsing disease, 26 (49.1%) were treated with pembrolizumab and 27 (50.9%) were treated with chemotherapy as first-line therapy. Fifteen patients with non-early relapsing disease were treated with chemotherapy. Early relapsing disease was associated with shorter progression-free survival and overall survival than non-early relapsing disease. Pembrolizumab was associated with longer progression-free survival and survival with disease control than chemotherapy in patients with early relapsing disease. There was no significant difference in overall survival between pembrolizumab and chemotherapy, but overall survival plateau with a long tail was observed in pembrolizumab. CONCLUSIONS: First-line pembrolizumab in earlier clinical settings for highly malignant tumors might improve the prognosis of patients with early relapsing disease after the receipt of platinum-based perioperative chemotherapy.

Organ-Specific and Mixed Responses to Pembrolizumab in Patients with Unresectable or Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study.

To investigate the organ-specific response and clinical outcomes of mixed responses (MRs) to immune checkpoint inhibitors (ICIs) for unresectable or metastatic urothelial carcinoma (ur/mUC), we retrospectively analyzed 136 patients who received pembrolizumab. The total objective response rate (ORR) and organ-specific ORR were determined for each lesion according to the Response Evaluation Criteria in Solid Tumors version 1.1 as follows: (i) complete response (CR), (ii) partial response (PR), (iii) stable disease (SD), and (iv) progressive disease (PD). Most of the organ-specific ORR was 30−40%, but bone metastasis was only 5%. There was a significant difference in overall survival (OS) between responders and non-responders with locally advanced lesions and lymph node, lung, or liver metastases (HR 9.02 (3.63−22.4) p < 0.0001; HR 3.63 (1.97−6.69), p < 0.0001; HR 2.75 (1.35−5.59), p = 0.0053; and HR 3.17 (1.00−10.0), p = 0.049, respectively). MR was defined as occurring when PD happened in one lesion plus either CR or PR occurred in another lesion simultaneously, and 12 cases were applicable. MR was significantly associated with a poorer prognosis than that of the responder group (CR or PR; HR 0.09 (0.02−0.35), p = 0.004). Patients with bone metastases benefitted less. Care may be needed to treat patients with MR as well as patients with pure PD. Further studies should be conducted in the future.

Risk factors for radiation pneumonitis after rotating gantry intensity-modulated radiation therapy for lung cancer.

The risk factors for severe radiation pneumonitis (RP) in patients with lung cancer who undergo rotating gantry intensity-modulated radiation therapy (IMRT) using volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT) are poorly understood. Fifty-two patients who received rotating gantry IMRT for locally advanced lung cancer were included in this retrospective study. In total, 31 and 21 patients received VMAT and HT, respectively. The median follow-up duration was 14 months (range, 5.2-33.6). Twenty (38%) and eight (15%) patients developed grade ≥ 2 and ≥ 3 RP, respectively. In multivariate analysis, lung V5 ≥ 40% was associated with grade ≥ 2 RP (P = 0.02), and past medical history of pneumonectomy and total lung volume ≤ 3260 cc were independently associated with grade ≥ 3 RP (P = 0.02 and P = 0.03, respectively). Rotating gantry IMRT was feasible and safe in patients with lung cancer undergoing definitive radiotherapy. Reducing lung V5 may decrease the risk of symptomatic RP, and care should be taken to avoid severe RP after radiotherapy in patients with a past medical history of pneumonectomy and small total lung volume.

Accuracy of Percutaneous Pedicle Screw Placement after Single-Position versus Dual-Position Insertion for Lateral Interbody Fusion and Pedicle Screw Fixation Using Fluoroscopy.

STUDY DESIGN: Retrospective study. PURPOSE: The purpose of this study was to compare the accuracy of percutaneous pedicle screw (PPS) placement between prone and lateral decubitus positions during lateral lumbar interbody fusion (LLIF) and to evaluate the tendency of PPS positioning based on simple computed tomography measurements with patients in the lateral decubitus position. OVERVIEW OF LITERATURE: There is insufficient information in the literature regarding the accuracy of inserting a PPS using fluoroscopy in patients in the lateral decubitus position. METHODS: We included 62 patients who underwent combined LLIF surgery and PPS fixation for degenerative lumbar spondylolisthesis with spinal canal stenosis. We compared the patient demographics and the accuracy of fluoroscopy-guided PPS placement between two groups: patients who remained in the lateral decubitus position for the pedicle screw fixation (single-position surgery [SPS] group) and those who were turned to the prone position (dual-position surgery [DPS] group). RESULTS: There were 40 patients in the DPS group and 22 in the SPS group. Of the 292 PPSs, only 12 were misplaced. In other words, 280/292 screws (95.9%) were placed correctly in the pedicle's cortical shell (grade 0). PPS insertion did not cause neurological, vascular, or visceral injuries in either group. The breach rates for the DPS and SPS groups were 4.1% (grade 1, 5 screws; grade 2, 3 screws; grade 3, 0 screw) and 4.1% (grade 1, 2 screws; grade 2, 2 screws; grade 3, 0 screw), respectively. Although there were no statistically significant differences, the downside PPS had more screw malpositioning than the upside PPS. CONCLUSIONS: We found that PPS insertion with the patient in the decubitus position under fluoroscopic guidance might be as safe and reliable a technique as PPS insertion in the prone position, with a misplacement rate similar to that previously published.

Correlational analysis of chemokine and inflammatory cytokine expression in the intervertebral disc and blood in patients with lumbar disc disease.

The involvement of intervertebral disc (IVD) tissues, whole blood (WB) cytokines, and chemokines in pain in patients with lumbar degenerative disc disease (LDD) is unknown. We investigated the relationships between inflammatory cytokines and chemokines in human IVD tissues and WB samples and their association with pain. Expression levels of chemokines and cytokine gene expression were measured in samples from 20 patients with LDD and compared between IVD tissues and WB samples. The associations between WB chemokine and cytokine gene expression levels and pain intensity (numeric rating scale) were also analyzed. The mRNA of C-C chemokine ligand 20 (CCL20), C-C chemokine receptor 6 (CCR6), interleukin-6 (IL-6), IL-1ß, IL-17, and tumor necrosis factor-α (TNF-α) was expressed in degenerated IVD tissues. Pearson's product-moment correlation analysis produced positive correlations between CCR6 and IL-6 expression levels in IVD tissues (r = 0.845, p < 0.001) and WB samples (r = 0.963, p < 0.001). WB IL-6 and CCR6 mRNA expression levels correlated significantly with present pain, maximum pain, and average pain. By contrast, low back pain (LBP) did not correlate with serum chemokine/cytokine expression. This is the first study to report correlations between chemokine and inflammatory cytokine gene expression levels in IVD tissues and WB samples in patients with LDD in relation to pain intensity. WB CCR6 and IL-6 gene expression levels correlated significantly with present pain, maximum pain, and average pain, but not with LBP. These data provide a new understanding of the role of chemokines and inflammatory cytokines in patients with LDD and may lead to new treatment strategies for pain.

Effect of low body mass index on clinical recovery after fusion surgery for osteoporotic vertebral fracture: A retrospective, multicenter study of 237 cases.

A retrospective multicenter study. Body mass index (BMI) is recognized as an important determinant of osteoporosis and spinal postoperative outcomes; however, the specific impact of BMI on surgery for osteoporotic vertebral fractures (OVFs) remains inconclusive. This retrospective multicenter study investigated the impact of BMI on clinical outcomes following fusion surgery for OVFs. 237 OVF patients (mean age, 74.3 years; 48 men and 189 women) with neurological symptoms who underwent spinal fusion were included in this study. Patients were grouped by World Health Organization BMI categories: low BMI (<18.5 kg/m2), normal BMI (≥18.5 and <25 kg/m2), and high BMI (≥25 kg/m2). Patients' backgrounds, surgical method, radiological findings, pain measurements, activities of daily living (ADL), and postoperative complications were compared after a mean follow-up period of 4 years. As results, the proportion of patients able to walk independently was significantly smaller in the low BMI group (75.0%) compared with the normal BMI group (89.9%; P = .01) and the high BMI group (94.3%; P = .04). Improvement in the visual analogue scale for leg pain was significantly less in the low BMI group than the high BMI group (26.7 vs 42.8 mm; P = .046). Radiological evaluation, the Frankel classification, and postoperative complications were not significantly different among all 3 groups. Improvement of pain intensity and ADL in the high BMI group was equivalent or non-significantly better for some outcome measures compared with the normal BMI group. Leg pain and independent walking ability after fusion surgery for patients with OVFs improved less in the low versus the high BMI group. Surgeons may want to carefully evaluate at risk low BMI patients before fusion surgery for OVF because poor clinical results may occur.

Conformational changes of α-helical peptides with different hydrophobic residues induced by metal-ion binding.

We designed peptides that formed helix bundle structures upon binding of the metal-ions to His residues to form a stable hydrophobic core, in order to analyze the effects of Ala, Val, Ile, and Leu residues, located in the hydrophobic core, together with His, on the conformational changes in respective peptides designated as HA, HV, HI, and HL, respectively. Circular dichroism measurements showed that HV and HI changed from random coil to helix bundle structures upon Zn2+ binding, similar to that observed for HA, while HL existed in the helix bundle structure even in the absence of Zn2+. Electron spin resonance measurements showed that Cu2+ coordination of HI and HL was quite different from that of HA and HV, indicating that HA and HV fluctuated to a greater extent in the solution, despite that their apparent α-helical contents being similar to those of HI and HL. This was also supported by the results obtained from the analyses of thermal stabilities. The change in the structural fluctuation for each peptide upon Zn2+ binding was evaluated based on binding thermodynamics using isothermal titration calorimetry. The structural flexibility in the metal-ion-bound state was found to be in the order HA > HV > HI, and that in the metal-ion-unbound state was found to be greater for HI than that for HL.

A first report of tumour-tracking radiotherapy with helical tomotherapy for lung and liver tumours: A double case report.

There are only a limited number of previous reports on clinical cases using tumour tracking with tomotherapy. Therefore, we present two cases of patients treated with tumour tracking with tomotherapy. First, a 74-year-old man with an inoperable lung cancer type T1bN0M0 underwent stereotactic body radiotherapy at a total dose of 48 Gy in four fractions. Second, a 68-year-old man with hepatocellular carcinoma with a portal venous tumour thrombosis and history of liver stereotactic body radiotherapy with fiducial marker implantation received radiotherapy at a total dose of 48 Gy in 20 fractions. The results of patient-specific quality assurance and tracking radiotherapy were sufficient to irradiate tumours. Tumour tracking with tomotherapy successfully delivered radiation in a total of 24 treatment fractions in both patients. Tumour tracking with tomotherapy is feasible in lung and liver cancer treatment. This study's findings suggest the clinical use of tumour tracking with tomotherapy.

Characteristics of a bolus created using thermoplastic sheets for postmastectomy radiation therapy.

This study applied a "shell bolus," an immobilizing thermoplastic shell locally thickened with extra layers over the radiation target, during postmastectomy radiation therapy (PMRT). We performed ion chamber and film measurements for a solid water phantom for thermoplastic sheets and a gel bolus for dosimetric characterization using a 6-MV X-ray flattening-filter-free (FFF) beam. The air gaps between the body surface for the gel and shell bolus were measured using computed tomography (CT) images in patients who underwent PMRT. This included seven and 13 patients treated with the gel and shell boluses, respectively. A comparison of the dose differences between a 10-mm gel bolus and a 9.6-mm-thick thermoplastic sheet at the surface and 5 cm below the surface showed a 4.2% higher surface dose and 0.5% lower dose at 5-cm depth for the thermoplastic sheet compared to those for the gel bolus. The mean (p = 0.029) and maximum (p < 0.001) air gaps of the shell bolus were significantly thinner than those of the gel bolus. Thus, the shell bolus provided a close fit and robust bolus effect. In addition, the shell bolus reduced respiratory motion and eliminated the need for skin marking. Therefore, this system can be effectively used as a bolus for PMRT.

Generation of macrophages with altered viral sensitivity from genome-edited rhesus macaque iPSCs to model human disease.

Because of their close biological similarity to humans, non-human primate (NHP) models are very useful for the development of induced pluripotent stem cell (iPSC)-based cell and regenerative organ transplantation therapies. However, knowledge on the establishment, differentiation, and genetic modification of NHP-iPSCs, especially rhesus macaque iPSCs, is limited. We succeeded in establishing iPSCs from the peripheral blood of rhesus macaques (Rh-iPSCs) by combining the Yamanaka reprograming factors and two inhibitors (GSK-3 inhibitor [CHIR 99021] and MEK1/2 inhibitor [PD0325901]) and differentiated the cells into functional macrophages through hematopoietic progenitor cells. To confirm feasibility of the Rh-iPSC-derived macrophages as a platform for bioassays to model diseases, we knocked out TRIM5 gene in Rh-iPSCs by CRISPR-Cas9, which is a species-specific HIV resistance factor. TRIM5 knockout (KO) iPSCs had the same differentiation potential to macrophages as did Rh-iPSCs, but the differentiated macrophages showed a gain of sensitivity to HIV infection in vitro. Our reprogramming, gene editing, and differentiation protocols used to obtain Rh-iPSC-derived macrophages can be applied to other gene mutations, expanding the number of NHP gene therapy models.

Simultaneous translation on two rods improves the correction and apex translocation in adolescent patients with hypokyphotic scoliosis.

OBJECTIVE: The objectives of this study were to apply the simultaneous translation on two rods (ST2R) maneuver involving rods contoured with a convexity at the desired thoracic kyphosis (TK) apex level and to assess the effects on the ability to support triplanar deformity corrections, including TK apex improvement, in patients with hypokyphotic adolescent idiopathic scoliosis (AIS). METHODS: Using retrospective analysis, the authors examined the digital records that included 2- to 4-week, 1-year, and 2-year postoperative radiographic follow-up data of female hypokyphotic (TK < 20°) AIS patients (Lenke type 1-3) treated with ST2R. The authors assessed the corrections of triplanar deformities by examining the main Cobb angle, TK, rib hump, apical vertebral rotation, Scoliosis Research Society 22-item questionnaire scores, and TK apex translocation. In order to better grasp the potential of ST2R, the outcomes were compared with those of a historical matched case-control cohort treated with a standard rod rotation (RR) maneuver. RESULTS: Data were analyzed for 25 AIS patients treated with ST2R and 27 patients treated with RR. The ST2R group had significant improvements in the main Cobb angle and TK, reduction in the rib hump size at each time point, and a final correction rate of 72%. ST2R treatment significantly increased the kyphosis apex by an average of 2.2 levels. The correction rate was higher at each time point in the ST2R group than in the RR group. ST2R engendered favorable TK corrections, although the differences were nonsignificant, at 2 years compared with the RR group (p = 0.056). The TK apex location was significantly improved in the ST2R cohort (p < 0.001). At the 1-month follow-up, hypokyphosis was resolved in 92% of the ST2R cohort compared with 30% of the RR cohort. CONCLUSIONS: Resolving hypokyphotic AIS remains challenging. The ST2R technique supported significant triplanar corrections, including TK apex translocation and restoration of hypokyphosis in most patients. Comparisons with the RR cohort require caution because of differences in the implant profile. However, ST2R significantly improved the coronal and sagittal corrections. It also allowed for distribution of correctional forces over two rod implants instead of one, which should decrease the risk of screw pullout and rod flattening. It is hoped that the description here of commercially available reducers used with the authors' surgical technique will encourage other clinicians to consider using the ST2R technique.

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: In this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. RESULTS: Of 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non-squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. CONCLUSION: Addition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non-small-cell lung cancer, particularly squamous cell carcinoma.

Short-term comparison of preoperative and postoperative pain after indirect decompression surgery and direct decompression surgery in patients with degenerative spondylolisthesis.

The purpose of this study was to compare the short-term clinical outcomes between extreme lateral interbody fusion (XLIF) and minimally invasive surgery (MIS)-transforaminal interbody fusion (TLIF) in patients with degenerative spondylolisthesis with stenosis. One hundred-six patients were enrolled; 44 were treated with MIS-TLIF (direct decompression group; DP), and 62 were treated with XLIF (indirect decompression group; IDP). Perioperative indexes included operation time and intraoperative bleeding. Perioperative indexes preoperative and postoperative numeric rating scale (NRS) scores for low back pain (NRS-BP), leg pain (NRS-LP), and leg numbness (NRS-LN), and the preoperative score on the Japanese version of the painDETECT questionnaire (PDQ-J) were also assessed. The average follow-up period for the collection of NRS scores was 12.6 months. The operation time was significantly shorter in the IDP than in the DP group (109.9 ± 35.4 vs. 153.3 ± 50.9 min; p < 0.001). Intraoperative blood loss was also significantly less in the IDP group than in the DP group (85.4 ± 125.4 vs. 258.3 ± 220.4 mL; p < 0.001). The PDQ-J score and preoperative NRS scores (NRS-BP, NRS-LP, and NRS-LN) did not differ significantly between groups. Less improvement in the NRS-BP (ΔNRS-BP) was observed in the DP group than in the IDP group (p < 0.05). Although pain improved after surgery in both groups, IDP surgery was advantageous in minimizing bleeding and preserving posterior support elements such as the facet joints, lamina, and paraspinal muscles. These findings suggest that this may have contributed to the higher rate of improvement in low back pain compared with DP surgery.

Facet joint violation after single-position versus dual-position lateral interbody fusion and percutaneous pedicle screw fixation: A comparison of two techniques.

BACKGROUND: The purpose of this study was to compare the incidence of facet joint violation (FJV) after placement of percutaneous pedicle screws (PPSs) in 2 cohorts of patients who underwent surgery in a single position or dual position following lateral lumbar interbody fusion (LLIF) (extreme lateral interbody fusion [XLIF]). METHODS: We reviewed 82 patients who underwent combined XLIF surgery and PPS fixation for the treatment of degenerative lumbar spinal disorders. Patient demographics were compared between 2 groups: those who remained in the lateral decubitus position for PPS fixation (SP group) and those who were turned to the prone position (DP group). Postoperative axial computed tomography scans were evaluated independently for FJV according to the following classification: grade 0, no impingement; grade 1, screw head in contact/suspected to be in contact with the facet joint; and grade 2, screw clearly invaded the facet joint. RESULTS: A total of 349 screws were graded. Using the consensus grades, the incidence of FJV was 13.2% (46/349), but the incidence of FJV did not differ significantly according to the position of the patient during PPS insertion (SP group; 15.4%, DP group; 10.8%, P = 0.204). CONCLUSIONS: Although the incidence of FJV after PPS insertion did not differ between the prone and lateral decubitus positions, grade 2 FJV was observed only in the SP group. To avoid FJV, the surgeon should pay close attention to the facet joints when inserting PPSs with the patient in a lateral decubitus position.