PD-1 and TIGIT downregulation distinctly affect the effector and early memory phenotypes of CD19-targeting CAR T cells.

CD19-targeting chimeric antigen receptor (CAR) T cells have become an important therapeutic option for patients with relapsed and refractory B cell malignancies. However, a significant portion of patients still do not benefit from the therapy owing to various resistance mechanisms, including high expression of multiple inhibitory immune checkpoint receptors. Here, we report a lentiviral two-in-one CAR T approach in which two checkpoint receptors are downregulated simultaneously by a dual short hairpin RNA cassette integrated into a CAR vector. Using this system, we evaluated CD19-targeting CAR T cells in the context of four different checkpoint combinations-PD-1/TIM-3, PD-1/LAG-3, PD-1/CTLA-4, and PD-1/TIGIT-and found that CAR T cells with PD-1/TIGIT downregulation uniquely exerted synergistic antitumor effects. Importantly, functional and phenotypic analyses suggested that downregulation of PD-1 enhances short-term effector function, whereas downregulation of TIGIT is primarily responsible for maintaining a less differentiated/exhausted state, providing a potential mechanism for the observed synergy. The PD-1/TIGIT-downregulated CAR T cells generated from diffuse large B cell lymphoma patient-derived T cells also showed robust antitumor activity and significantly improved persistence in vivo. The efficacy and safety of PD-1/TIGIT-downregulated CD19-targeting CAR T cells are currently being evaluated in adult patients with relapsed or refractory large B cell lymphoma (ClinicalTrials.gov: NCT04836507).

Comparison of the effectiveness and safety of bioactive glass ceramic to allograft bone for anterior cervical discectomy and fusion with anterior plate fixation.

Recently, a bioactive glass ceramic (BGC) has been developed for use as intervertebral cages for anterior cervical discectomy and fusion (ACDF). However, the effectiveness and safety of BGC cages remain to be evaluated. We completed a retrospective comparison of the radiological and clinical outcomes of 36 patients (52 levels) who underwent ACDF with a BGC cage and 35 patients (54 levels) using allograft bone. The following variables were compared between the two groups: the visual analog (VAS) neck and arm pain score and the neck disability index (NDI), measured before surgery and 1 year after; the change in Cobb's angle, between the C2 and C7 vertebrae, the global sagittal angle, and disc height compared from before surgery to 1 year after; and the rate of spinal fusion and cage subsidence at 1 and 2 years after surgery. The VAS and NDI scores were not different between the two groups. Similarly, the spinal fusion rate was not different between the BGC and allograft bone group at 1 year (73% and 87%, respectively; p = 0.07) and 2 years (94% and 91%, respectively; p = 0.54) after surgery. However, the rate of cage subsidence was higher in the allograft bone (43%) than the BGC (19%) group (p = 0.03), as was the rate of instrument-related failure (p = 0.028), with a specifically higher incidence of implant fracture or failure in the allograft bone group (p = 0.025). Overall, our findings indicate that BGC cages provide a feasible and safe alternative to allograft bone for ACDF.

Characterization of focal liver lesions using the stretched exponential model: comparison with monoexponential and biexponential diffusion-weighted magnetic resonance imaging.

OBJECTIVE: To compare the stretched exponential model of diffusion-weighted imaging (DWI) with monoexponential and biexponential models in terms of the ability to characterize focal liver lesions (FLLs). METHODS: This retrospective study included 180 patients with FLLs who underwent magnetic resonance imaging including DWI with nine b values at 3.0 T. The distributed diffusion coefficient (DDC) and intravoxel diffusion heterogeneity index (α) from a stretched exponential model; true diffusion coefficient (Dt), pseudo-diffusion coefficient (Dp), and perfusion fraction (f) from a biexponential model; and apparent diffusion coefficient (ADC) were calculated for each lesion. Diagnostic performances of the parameters were assessed through receiver operating characteristic (ROC) analysis. For 20 patients with treated hepatic metastases, the correlation between the DWI parameters and the percentage of tumor necrosis on pathology was evaluated using the Spearman correlation coefficient. RESULTS: DDC had the highest area under the ROC curve (AUC, 0.905) for differentiating malignant from benign lesions, followed by Dt (0.903) and ADC (0.866), without significant differences among them (DDC vs. Dt, p = 0.946; DDC vs. ADC, p = 0.157). For distinguishing hypovascular from hypervascular lesions, and hepatocellular carcinoma from metastasis, f had a significantly higher AUC than the other DWI parameters (p < 0.05). The α had the strongest correlation with the degree of tumor necrosis (ρ = 0.655, p = 0.002). CONCLUSION: The DDC from stretched exponential model of DWI demonstrated excellent diagnostic performance for differentiating malignant from benign FLLs. The α is promising for evaluating the degree of necrosis in treated metastases. KEY POINTS: • The stretched exponential DWI model is valuable for characterizing focal liver lesions. • The DDC from stretched exponential model shows excellent performance for differentiating malignant from benign focal liver lesions. • The α from stretched exponential model is promising for evaluating the degree of necrosis in hepatic metastases after chemotherapy.

Genomic and Proteomic Evidences for Exopolysaccharide Biosynthesis in Sphingobium chungbukense DJ77.

Sphingobium chungbukense DJ77 is a Gram-negative bacterium has metabolic capability of producing exopolysaccharide (EPS) as a potential reducing and stabilizing agent for metallic nanoparticle synthesis. In this study, we investigated the genomic and proteomic analysis to verify metabolic pathway and involved genes and enzymes related to EPS biosynthesis in S. chungbukense DJ77. End-sequencing results of randomly selected fosmid library, which were prepared from high molecular weight DNA of S. chungbukense DJ77, showed identity to sequences from genes related the EPS biosynthesis pathways in several bacteria. We also observed that proteomic responses in S. chungbukense DJ77 by heterogeneously expressing gelA and gelN involved in gellan biosynthesis in Sphingomonas elodea. Comparative two-dimensional gel electrophoresis revealed that both GelA and GelN altered internal expression levels of proteins involved in EPS biosynthesis in S. chungbukense DJ77. The results might provide the genomic and proteomic evidences for presence of EPS biosynthesis pathways in S. chungbukense DJ77.

Detecting and Discriminating Shigella sonnei Using an Aptamer-Based Fluorescent Biosensor Platform.

In this paper, a Whole-Bacteria SELEX (WB-SELEX) strategy was adopted to isolate specific aptamers against Shigella sonnei. Real-time PCR amplification and post-SELEX experiment revealed that the selected aptmers possessed a high binding affinity and specificity for S. sonnei. Of the 21 aptamers tested, the C(t) values of the SS-3 and SS-4 aptamers (Ct = 13.89 and Ct = 12.23, respectively) had the lowest value compared to other aptamer candidates. The SS-3 and SS-4 aptamers also displayed a binding affinity (KD) of 39.32 ± 5.02 nM and 15.89 ± 1.77 nM, respectively. An aptamer-based fluorescent biosensor assay was designed to detect and discriminate S. sonnei cells using a sandwich complex pair of SS-3 and SS-4. The detection of S. sonnei by the aptamer based fluorescent biosensor platform consisted of three elements: (1) 5'amine-SS-4 modification in a 96-well type microtiter plate surface (N-oxysuccinimide, NOS) as capture probes; (2) the incubation with S. sonnei and test microbes in functionalized 96 assay wells in parallel; (3) the readout of fluorescent activity using a Cy5-labeled SS-3 aptamer as the detector. Our platform showed a significant ability to detect and discriminate S. sonnei from other enteric species such as E. coli, Salmonella typhimurium and other Shigella species (S. flexneri, S. boydii). In this study, we demonstrated the feasibility of an aptamer sensor platform to detect S. sonnei in a variety of foods and pave the way for its use in diagnosing shigellosis through multiple, portable designs.

Thoracic Duct Embolization for Treatment of Chyle Leakage After Thyroidectomy and Neck Dissection.

OBJECTIVE: This study aimed to evaluate the safety and efficacy of intranodal lymphangiography and thoracic duct embolization (TDE) for chyle leakage (CL) after thyroid surgery. MATERIALS AND METHODS: Fourteen patients who underwent intranodal lymphangiography and TDE for CL after thyroid surgery were included in this retrospective study. Among the 14 patients, 13 underwent bilateral total thyroidectomy with neck dissection (central compartment neck dissection [CCND], n = 13; left modified radical neck dissection (MRND), n = 11; bilateral MRND, n = 2), and one patient underwent left hemithyroidectomy with CCND. Ten patients (76.9%) had high-output CL (> 500 mL/d). Before the procedure, surgical intervention was attempted in three patients (thoracic duct ligation, n = 1; lymphatic leakage site ligation, n = 2). Lymphangiographic findings, technical and clinical successes, and complications were analyzed. Technical success was defined as the successful embolization of the thoracic duct after access to the lymphatic duct via the transabdominal route. Clinical success was defined as the resolution of CL or surgical drain removal. RESULTS: On lymphangiography, ethiodized oil leakage near the surgical bed was identified in 12 of 14 patients (85.7%). The technical success rate of TDE was 78.6% (11/14). Transabdominal antegrade access was not feasible due to the inability to visualize the identifiable cisterna chyli or a prominent lumbar lymphatic duct. Among patients who underwent a technically successful TDE, the clinical success rate was 90.1% (10/11). The median time from the procedure to drain removal was 3 days (with a range of 1-13 days) for the 13 patients who underwent surgical drainage. No CL recurrence was observed during the follow-up period (ranging from 2-44 months; median, 8 months). There were no complications, except for one case of chylothorax that developed after TDE. CONCLUSION: TDE appears to be a safe and effective minimally invasive treatment option for CL after thyroid surgery, with acceptable technical and clinical success rates.

A Propensity Score-Matched Cohort Study Comparing 3 Different Spine Pedicle Screw Fixation Methods: Freehand, Fluoroscopy-Guided, and Robot-Assisted Techniques.

OBJECTIVE: This study aimed to compare the accuracy of robotic spine surgery and conventional pedicle screw fixation in lumbar degenerative disease. We evaluated clinical and radiological outcomes to demonstrate the noninferiority of robotic surgery. METHODS: This study employed propensity score matching and included 3 groups: robot-assisted mini-open posterior lumbar interbody fusion (PLIF) (robotic surgery, RS), c-arm guided minimally invasive surgery transforaminal lumbar interbody fusion (C-arm guidance, CG), and freehand open PLIF (free of guidance, FG) (54 patients each). The mean follow-up period was 2.2 years. The preoperative spine condition was considered. Accuracy was evaluated using the Gertzbein-Robbins scale (GRS score) and Babu classification (Babu score). Radiological outcomes included adjacent segmental disease (ASD) and mechanical failure. Clinical outcomes were assessed based on the visual analogue scale, Oswestry Disability Index, 36-item Short Form health survey, and clinical ASD rate. RESULTS: Accuracy was higher in the RS group (p < 0.01) than in other groups. The GRS score was lower in the CG group, whereas the Babu score was lower in the FG group compared with the RS group. No significant differences were observed in radiological and clinical outcomes among the 3 groups. Regression analysis identified preoperative facet degeneration, GRS and Babu scores as significant variables for radiological and clinical ASD. Mechanical failure was influenced by the GRS score and patients' age. CONCLUSION: This study showed the superior accuracy of robotic spine surgery compared with conventional techniques. When combined with minimally invasive surgery, robotic surgery is advantageous with reduced ligament and muscle damage associated with traditional open procedures.

Clinical course of patients with hepatocellular carcinoma who experienced radiologic complete response after radioembolization.

Purpose: The purpose of this study is to elucidate the patterns of recurrence of hepatocellular carcinoma and to analyze factors that can predict recurrence after complete response to radioembolization. Materials and methods: A total of 289 consecutive patients who underwent radioembolization for the treatment of hepatocellular carcinoma at a single tertiary center were retrospectively reviewed. Baseline characteristics were collected and compared between the group showing complete response and the group showing noncomplete response. Data on recurrence status, time to recurrence, and the patterns of recurrence among the patients who showed radiologic complete response were collected. The group that maintained complete response and the group that experienced recurrence were compared, and the risk factors affecting recurrence were evaluated by logistic regression analysis. Results: The complete response rate was 24.9% (73/289). Age, sex, tumor markers, maximum tumor diameter, multiplicity, presence of vascular invasion, and target radiation dose were significantly different between the complete response and noncomplete response groups. The recurrence rate after complete response was 38.4% (28/73), and 67.9% (19/28) of recurrences occurred by 8 months after complete response. Eight patients who underwent resection/transplantation after complete response experienced no recurrence. Multiple tumors and a lower target radiation dose were independent risk factors of recurrence after complete response in the multivariate logistic regression. Conclusion: Hepatocellular carcinoma recurrence following complete response after radioembolization is not uncommon and frequently occurs within 1 year after complete response. Multiple tumors and a lower target radiation dose may be risk factors for recurrence.

Structure and function of a HECT domain ubiquitin-binding site.

The Rsp5 ubiquitin ligase contains a non-covalent binding site for ubiquitin within the amino-terminal lobe (N-lobe) of the HECT domain, and the X-ray crystal structure of the HECT-ubiquitin complex has been determined. Hydrophobic patch residues of ubiquitin (L8, I44, V70) were crucial for interaction with Rsp5, and amino-acid alterations at the Rsp5-binding interface resulted in defects in polyubiquitination. Our results support a model in which the N-lobe-binding site acts to localize and orient the distal end of the ubiquitin chain to promote conjugation of the next ubiquitin molecule.

Thermal Grill Illusion in Chronic Lower Back Pain: A Case-Control Study.

Purpose: This study aimed to use thermal grill illusion (TGI), an experimental model of pain processing and central mechanisms, to evaluate the perception of TGI-related sensations or pain in patients with chronic lower back pain (CLBP). Patients and Methods: The perception of TGI (warmth/heat, cold, unpleasantness, pain, burning, stinging, and prickling) was examined in 66 patients with CLBP and compared with that in 22 healthy participants. The visual analog scale (VAS) scores for CLBP, Oswestry Disability Index (ODI), and 12-Item Short Form Survey (SF-12) scores were obtained from the included patients with CLBP. Results: The CLBP group showed a less intense perception of TGI for sensations of warmth/heat, unpleasantness, and pain than the control group. The CLBP group felt burning sensations lesser than the control (2.77 vs 4.55, P=0.016). In the CLBP group, there were significant correlations between the ODI and the degree of unpleasantness (r=0.381, P=0.002) and prickling sensation (r=0.263, P=0.033). There were also significant correlations between the mental component score of the SF-12 and the degree of warmth/heat (r=-0.246, P=0.046), unpleasantness (r=-0.292, P=0.017), pain (r=-0.292, P=0.017), and burning sensations (r=-0.280, P=0.023). Conclusion: Our results may be useful for clinicians to evaluate the effectiveness of drugs or interventions to manage centralized LBP.

Balloon Bronchoplasty for the Treatment of Bronchial Stenosis After Lung Transplantation: A Single-Center 10-Year Experience.

OBJECTIVE: To assess the safety and efficacy of balloon dilatation under dual guidance using fluoroscopy and bronchoscopy for treating bronchial stenosis following lung transplantation (LT), and to elucidate the factors associated with patency after the procedure. MATERIALS AND METHODS: From September, 2012, to April, 2021, 50 patients (mean age ± standard deviation, 54.4 ± 12.2 years) with bronchial stenosis among 361 recipients of LT were retrospectively analyzed. The safety of balloon dilatation was assessed by evaluating procedure-related complications. Efficacy was assessed by evaluating the technical success, primary patency, and secondary patency. Primary and secondary cumulative patency rates were calculated using the Kaplan-Meier method. The factors associated with patency after the procedure were evaluated using multivariable Cox hazard proportional regression analysis. RESULTS: In total, 65 bronchi were treated with balloon dilatation in 50 patients. The total number of treatment sessions was 277 and the technical success rate was 99.3% (275/277 sessions). No major procedure-related complications were noted. During the mean follow-up period of 34.6 ± 30.8 months, primary patency was achieved in 12 of 65 bronchi (18.5%). However, the patency rate improved to 76.9% (50 of 65 bronchi) after repeated balloon dilatation (secondary patency). The 6-month, 1-year, 3-year, and 5-year secondary patency rates were 95.4%, 90.8%, 83.1%, and 78.5%, respectively. The presence of clinical symptoms was a significant prognostic factor associated with reduced primary patency (adjusted hazard ratio [HR], 0.465; 95% confidence interval [CI], 0.220-0.987). Early-stage treatment ≤ 6 months (adjusted HR, 3.588; 95% CI, 1.093-11.780) and prolonged balloon dilatation > 5 min (adjusted HR, 3.285; 95% CI, 1.018-10.598) were associated with significantly higher secondary patency. CONCLUSION: Repeated balloon dilatation was determined to be safe and effective for treating bronchial stenosis following LT. Early-stage treatment and prolonged balloon dilatation could significantly promote long-term patency.

Intrawound Vancomycin Powder Application for Preventing Surgical Site Infection Following Cranioplasty.

OBJECTIVE: Surgical site infection is the most detrimental complication following cranioplasty. In other surgical fields, intrawound vancomycin powder application has been introduced to prevent surgical site infection and is widely used based on results in multiple studies. This study evaluated the effect of intrawound vancomycin powder in cranioplasty compared with the conventional method without topical antibiotics. METHODS: This retrospective study included 580 patients with skull defects who underwent cranioplasty between August 1, 1998 and December 31, 2021. The conventional method was used in 475 (81.9%; conventional group) and vancomycin powder (1 g) was applied on the dura mater and bone flap in 105 patients (18.1%; vancomycin powder group). Surgical site infection was defined as infection of the incision, organ, or space that occurred after cranioplasty. Surgical site infection within 1-year surveillance period was compared between the conventional and vancomycin powder groups with logistic regression analysis. Penalized likelihood estimation method was used in logistic regression to deal with zero events. All local and systemic adverse events associated with topical vancomycin application were also evaluated. RESULTS: Surgical site infection occurred in 31 patients (5.3%) and all were observed in the conventional group. The median time between cranioplasty and detection of surgical site infection was 13 days (range, 4-333). Staphylococci were the most common organisms and identified in 25 (80.6%) of 31 cases with surgical site infections. The surgical site infection rate in the vancomycin powder group (0/105, 0.0%) was significantly lower than that in the conventional group (31/475, 6.5%; crude odds ratio [OR], 0.067; 95% confidence interval [CI], 0.006-0.762; adjusted OR, 0.068; 95% CI, 0.006-0.731; p=0.026). No adverse events associated with intrawound vancomycin powder were observed during the follow-up. CONCLUSION: Intrawound vancomycin powder effectively prevented surgical site infections following cranioplasty without local or systemic adverse events. Our results suggest that intrawound vancomycin powder is an effective and safe strategy for patients undergoing cranioplasty.

A genome-wide association study identifies a breast cancer risk variant in ERBB4 at 2q34: results from the Seoul Breast Cancer Study.

INTRODUCTION: Although approximately 25 common genetic susceptibility loci have been identified to be independently associated with breast cancer risk through genome-wide association studies (GWAS), the genetic risk variants reported to date only explain a small fraction of the heritability of breast cancer. Furthermore, GWAS-identified loci were primarily identified in women of European descent. METHODS: To evaluate previously identified loci in Korean women and to identify additional novel breast cancer susceptibility variants, we conducted a three-stage GWAS that included 6,322 cases and 5,897 controls. RESULTS: In the validation study using Stage I of the 2,273 cases and 2,052 controls, seven GWAS-identified loci [5q11.2/MAP3K1 (rs889312 and rs16886165), 5p15.2/ROPN1L (rs1092913), 5q12/MRPS30 (rs7716600), 6q25.1/ESR1 (rs2046210 and rs3734802), 8q24.21 (rs1562430), 10q26.13/FGFR2 (rs10736303), and 16q12.1/TOX3 (rs4784227 and rs3803662)] were significantly associated with breast cancer risk in Korean women (Ptrend < 0.05). To identify additional genetic risk variants, we selected the most promising 17 SNPs in Stage I and replicated these SNPs in 2,052 cases and 2,169 controls (Stage II). Four SNPs were further evaluated in 1,997 cases and 1,676 controls (Stage III). SNP rs13393577 at chromosome 2q34, located in the Epidermal Growth Factor Receptor 4 (ERBB4) gene, showed a consistent association with breast cancer risk with combined odds ratios (95% CI) of 1.53 (1.37-1.70) (combined P for trend = 8.8 × 10-14). CONCLUSIONS: This study shows that seven breast cancer susceptibility loci, which were previously identified in European and/or Chinese populations, could be directly replicated in Korean women. Furthermore, this study provides strong evidence implicating rs13393577 at 2q34 as a new risk variant for breast cancer.

Rescue of HIV-1 release by targeting widely divergent NEDD4-type ubiquitin ligases and isolated catalytic HECT domains to Gag.

Retroviruses engage the ESCRT pathway through late assembly (L) domains in Gag to promote virus release. HIV-1 uses a PTAP motif as its primary L domain, which interacts with the ESCRT-I component Tsg101. In contrast, certain other retroviruses primarily use PPxY-type L domains, which constitute ligands for NEDD4-type ubiquitin ligases. Surprisingly, although HIV-1 Gag lacks PPxY motifs, the release of HIV-1 L domain mutants is potently enhanced by ectopic NEDD4-2s, a native isoform with a naturally truncated C2 domain that appears to account for the residual titer of L domain-defective HIV-1. The reason for the unique potency of the NEDD4-2s isoform has remained unclear. We now show that the naturally truncated C2 domain of NEDD4-2s functions as an autonomous Gag-targeting module that can be functionally replaced by the unrelated Gag-binding protein cyclophilin A (CypA). The residual C2 domain of NEDD4-2s was sufficient to transfer the ability to stimulate HIV-1 budding to other NEDD4 family members, including the yeast homologue Rsp5, and even to isolated catalytic HECT domains. The isolated catalytic domain of NEDD4-2s also efficiently promoted HIV-1 budding when targeted to Gag via CypA. We conclude that the regions typically required for substrate recognition by HECT ubiquitin ligases are all dispensable to stimulate HIV-1 release, implying that the relevant target for ubiquitination is Gag itself or can be recognized by divergent isolated HECT domains. However, the mere ability to ubiquitinate Gag was not sufficient to stimulate HIV-1 budding. Rather, our results indicate that the synthesis of K63-linked ubiquitin chains is critical for ubiquitin ligase-mediated virus release.

Surgical Strategies and Perioperative Considerations for Cervical Deformity With Cerebral Palsy: A Comprehensive Review of the Literature.

The complex nature of the cervical spine makes surgical intervention challenging when treating cervical deformity in patients with cerebral palsy (CDCP). However, few studies have investigated the unique characteristics of cerebral palsy that create the need for surgery, the most effective surgical strategies, and the possible perioperative complications. The intended benefit and the potential risk of postoperative complications must be considered when deciding to operate for CDCP. Because the approach and correction strategy depend on the type of cervical deformity, as well as the patient's comorbidities and functional status, a customized strategy is needed. Perioperatively, botulinum toxin injections and muscle division techniques can help control excessive involuntary movements and improve the spinal fusion success rate. Surgical intervention for CDCP requires a multidisciplinary approach, and the information presented in this article is intended to help in the perioperative management and surgical treatment of CDCP.

Novel C-arm-based planning robotic spinal surgery in a cadaver model using quantitative accuracy assessment methodology.

BACKGROUND: This preclinical study emulating the clinical environment quantitatively analysed the accuracy of pedicle screw insertion using a navigated robotic system. METHODS: Pedicle screws were placed from T7 to L5 in the whole-body form of a cadaver. After the insertion of multiple artificial markers into each vertebra, errors between the planned insertion path and the inserted screw were quantified using the Gertzbein-Robbins system (GRS) and offset calculation. RESULTS: A total of 22 screws were placed. Almost all (95.45% [21/22]) were classified as GRS A or B, while one (4.55%) was GRS C. The mean and standard deviations of entry, tip, and angular offset were 1.78 ± 0.94 mm, 2.30 ± 1.01 mm, and 2.64 ± 1.05°, respectively. CONCLUSIONS: This study demonstrated that pedicle screw insertion using a navigated robotic system had high accuracy and safety. A future clinical study is necessary to validate our findings.

Single-Position Oblique Lumbar Interbody Fusion and Percutaneous Pedicle Screw Fixation under O-Arm Navigation: A Retrospective Comparative Study.

The insertion of pedicle screws in the lateral position without a position change has been reported. We completed a retrospective comparison of the radiologic and clinical outcomes of 36 patients who underwent either single-position oblique lateral lumbar interbody fusion (SP-OLIF) using the O-arm (36 cases) or conventional OLIF (C-OLIF) using the C-arm (20 cases) for L2-5 single-level lumbar degenerative diseases. Radiological parameters were analyzed, including screw accuracy (Gertzbein-Robbins classification system; GRS), segmental instability, and fusion status. Screw misplacement was defined as a discrepancy of ≥2 mm. Clinical outcomes, including visual analog scale, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), and postoperative complications, were assessed. The spinal fusion rate was not different between the SP-OLIF and C-OLIF groups one year after surgery (p = 0.536). The ODI score was lower (p = 0.015) in the SP-OLIF than the C-OLIF group. Physical (p = 0.000) and mental component summaries (p = 0.000) of the SF-36 were significantly higher in the SP-OLIF group. Overall complication rates, including revision, surgical site infection, ipsilateral weakness, and radicular pain/numbness, were not significantly different. SP-OLIF using the O-arm procedure is feasible, with acceptable accuracy, fusion rate, and complication rate. This may be an alternative to conventional two-stage operations.

Association of frailty with regional sagittal spinal alignment in the elderly.

The degenerative changes in the spine of the frail elderly gradually exacerbate the alignment of the spine as the degeneration progresses. This study was conducted to assess the relationship between frailty and spine sagittal alignment measured in terms of global, cervical, thoracic, and lumbo-pelvic parameters. In total, 101 patients aged 75 years and older hospitalized for spine surgery were prospectively enrolled. We evaluated spinal sagittal parameters by dividing them into global (C7 sagittal vertical axis [SVA] and T1 pelvic angle [T1PA]), cervical (the C2-7 Cobb angle, Jackson line, and C2-7 plumb line), thoracic (thoracic kyphosis [TK]), and lumbo-pelvic (pelvic tilt [PT] and pelvic incidence minus lumbar lordosis value [PI-LL]). Patient characteristics; the Fatigue, Resistance, Ambulation, Illness, Loss of Weight (FRAIL) scale; and sagittal spinal parameters were included in the analysis. Multiple regression analysis was performed to identify associations between the FRAIL scale and sagittal spinal parameters. The FRAIL scale showed correlations with global sagittal parameters (C7 SVA [ß = 0.225, p = 0.029] and T1PA [ß = 0.273, p = 0.008]) and lumbo-pelvic parameters (PT [ß = 0.294, p = 0.004] and PI-LL [ß = 0.323, p = 0.001). Cervical and thoracic parameters were not directly associated with the FRAIL scale. LL and PI-LL were associated with TK, and TK was associated with cervical parameters (the C2-7 Cobb angle, Jackson line and C2-7 plumb line). In conclusion, frailty status could be an important factor that influences sagittal spinal alignment in the elderly. In this study, it was found that frailty mainly affected the balance of lumbo-pelvic alignment, and consequently affected the balance of the whole spine.

Glycyrrhizin ameliorating sterile inflammation induced by low-dose radiation exposure.

Glycyrrhizin (GL) is a direct inhibitor of HMGB1 which acts as an alarmin when excreted into the extracellular space. High-dose radiation in radiotherapy induces collateral damage to the normal tissue, which can be mitigated by GL inhibiting HMGB1. The purpose of this study was to assess changes in HMGB1 and pro-inflammatory cytokines and to evaluate the protective effect of GL after low-dose radiation exposure. BALB/c mice were irradiated with 0.1 Gy (n = 10) and 1 Gy (n = 10) with GL being administered to half of the mice (n = 5, respectively) before irradiation. Blood and spleen samples were harvested and assessed for oxidative stress, HMGB1, pro-inflammatory cytokines, and cell viability. HMGB1 and pro-inflammatory cytokines increased and cell viability decreased after irradiation in a dose-dependent manner. Oxidative stress also increased after irradiation, but did not differ between 0.1 Gy and 1 Gy. With the pretreatment of GL, oxidative stress, HMGB1, and all of the pro-inflammatory cytokines decreased while cell viability was preserved. Our findings indicate that even low-dose radiation can induce sterile inflammation by increasing serum HMGB1 and pro-inflammatory cytokines and that GL can ameliorate the sterile inflammatory process by inhibiting HMGB1 to preserve cell viability.

Preoperative Cognitive Impairment as a Predictor of Postoperative Outcomes in Elderly Patients Undergoing Spinal Surgery for Degenerative Spinal Disease.

Cognitive status has been reported to affect the peri-operative and post-operative outcomes of certain surgical procedures. This prospective study investigated the effect of preoperative cognitive impairment on the postoperative course of elderly patients (n = 122, >65 years), following spine surgery for degenerative spinal disease. Data on demographic characteristics, medical history, and blood analysis results were collected. Preoperative cognition was assessed using the mini-mental state examination, and patients were divided into three groups: normal cognition, mild cognitive impairment, and moderate-to-severe cognitive impairment. Discharge destinations (p = 0.014) and postoperative cardiopulmonary complications (p = 0.037) significantly differed based on the cognitive status. Operation time (p = 0.049), white blood cell count (p = 0.022), platelet count (p = 0.013), the mini-mental state examination score (p = 0.033), and the Beck Depression Inventory score (p = 0.041) were significantly associated with the length of hospital stay. Our investigation demonstrated that improved understanding of preoperative cognitive status may be helpful in surgical decision-making and postoperative care of elderly patients with degenerative spinal disease.