Generation of single-round infectious rotavirus with a mutation in the intermediate capsid protein VP6.

Rotavirus causes severe diarrhea in infants. Although live attenuated rotavirus vaccines are available, vaccine-derived infections have been reported, which warrants development of next-generation rotavirus vaccines. A single-round infectious virus is a promising vaccine platform; however, this platform has not been studied extensively in the context of rotavirus. Here, we aimed to develop a single-round infectious rotavirus by impairing the function of the viral intermediate capsid protein VP6. Recombinant rotaviruses harboring mutations in VP6 were rescued using a reverse genetics system. Mutations were targeted at VP6 residues involved in virion assembly. Although the VP6-mutated rotavirus expressed viral proteins, it did not produce progeny virions in wild-type cells; however, the virus did produce progeny virions in VP6-expressing cells. This indicates that the VP6-mutated rotavirus is a single-round infectious rotavirus. Insertion of a foreign gene, and replacement of the VP7 gene segment with that of human rotavirus clinical isolates, was successful. No infectious virions were detected in mice infected with the single-round infectious rotavirus. Immunizing mice with the single-round infectious rotavirus induced neutralizing antibody titers as high as those induced by wild-type rotavirus. Taken together, the data suggest that this single-round infectious rotavirus has potential as a safe and effective rotavirus vaccine. This system is also applicable for generation of safe and orally administrable viral vectors.IMPORTANCERotavirus, a leading cause of acute gastroenteritis in infants, causes an annual estimated 128,500 infant deaths worldwide. Although live attenuated rotavirus vaccines are available, they are replicable and may cause vaccine-derived infections. Thus, development of safe and effective rotavirus vaccine is important. In this study, we report the development of a single-round infectious rotavirus that can replicate only in cells expressing viral VP6 protein. We demonstrated that (1) the single-round infectious rotavirus did not replicate in wild-type cells or in mice; (2) insertion of foreign genes and replacement of the outer capsid gene were possible; and (3) it was as immunogenic as the wild-type virus. Thus, the mutated virus shows promise as a next-generation rotavirus vaccine. The system is also applicable to orally administrable viral vectors, facilitating development of vaccines against other enteric pathogens.

Characterization of Sialic Acid-Independent Simian Rotavirus Mutants in Viral Infection and Pathogenesis.

Rotaviruses (RVs) are nonenveloped viruses that cause gastroenteritis in infants and young children. Sialic acid is an initial receptor, especially for animal RVs, including rhesus RV. Sialic acid binds to the VP8* subunit, a part of the outer capsid protein VP4 of RV. Although interactions between virus and glycan receptors influence tissue and host tropism and viral pathogenicity, research has long been limited to biochemical and structural studies due to the unavailability of an RV reverse genetics system. Here, we examined the importance of sialic acid in RV infections using recombinant RVs harboring mutations in sialic acid-binding sites in VP4 via a simian RV strain SA11-based reverse genetics system. RV VP4 mutants that could not bind to sialic acid had replicated to decreased viral titer in MA104 cells. Wild-type virus infectivity was reduced, while that of VP4 mutants was not affected in sialic acid-deficient cells. Unexpectedly, in vivo experiments demonstrated that VP4 mutants suppressed mouse pups' weight gain and exacerbated diarrhea symptoms compared to wild-type viruses. Intestinal contents enhanced VP4 mutants' infectivity. Thus, possibly via interactions with other unknown receptors and/or intestinal contents, VP4 mutants are more likely than wild-type viruses to proliferate in the murine intestine, causing diarrhea and weight loss. These results suggest that RVs binding sialic acid notably affect viral infection in vitro and viral pathogenesis in vivo. IMPORTANCE Various studies have been conducted on the binding of VP8* and glycans, and the direct interaction between purified VP8* and glycans has been investigated by crystalline structure analyses. Here, we used a reverse genetics system to generate rotaviruses (RVs) with various VP4 mutants. The generated mutant strains clarified the importance of glycan binding in vitro and in vivo. Moreover, even when VP4 mutants could not bind to sialic acid, they were able to bind to an unknown receptor. As RVs evolve, pathogenicity can also be modified by easily altering the glycans to which VP4 binds.

Genetic engineering strategy for generating a stable dsRNA virus vector using a virus-like codon-modified transgene.

IMPORTANCE: The stabilities of transgenes in RNA virus vectors differ between the genes of interest, but the molecular mechanisms determining genetic stability remain unknown. This study demonstrated that the stability of a transgene was affected by the nucleotide composition, and altering the codon usage of transgenes to resemble that of the viral genome significantly increased transgene stability in double-stranded RNA virus vectors. The virus-like codon modification strategy enabled generation of stable rotavirus and mammalian orthoreovirus vectors, which could be developed as machinery for gene delivery to the intestines and/or respiratory organs. This technology has further potential to be expanded to other RNA viruses.

N-Glycosylation of Rotavirus NSP4 Protein Affects Viral Replication and Pathogenesis.

Rotavirus (RV), the most common cause of gastroenteritis in children, carries a high economic and health burden worldwide. RV encodes six structural proteins and six nonstructural proteins (NSPs) that play different roles in viral replication. NSP4, a multifunctional protein involved in various viral replication processes, has two conserved N-glycosylation sites; however, the role of glycans remains elusive. Here, we used recombinant viruses generated by a reverse genetics system to determine the role of NSP4 N-glycosylation during viral replication and pathogenesis. The growth rate of recombinant viruses that lost one glycosylation site was as high as that of the wild-type virus. However, a recombinant virus that lost both glycosylation sites (glycosylation-defective virus) showed attenuated replication in cultured cell lines. Specifically, replications of glycosylation-defective virus in MA104 and HT29 cells were 10- and 100,000-fold lower, respectively, than that of the wild-type, suggesting that N-glycosylation of NSP4 plays a critical role in RV replication. The glycosylation-defective virus showed NSP4 mislocalization, delay of cytosolic Ca2+ elevation, and less viroplasm formation in MA104 cells; however, these impairments were not observed in HT29 cells. Further analysis revealed that assembly of glycosylation-defective virus was severely impaired in HT29 cells but not in MA104 cells, suggesting that RV replication mechanism is highly cell type dependent. In vivo mouse experiments also showed that the glycosylation-defective virus was less pathogenic than the wild-type virus. Taken together, the data suggest that N-glycosylation of NSP4 plays a vital role in viral replication and pathogenicity. IMPORTANCE Rotavirus is the main cause of gastroenteritis in young children and infants worldwide, contributing to 128,500 deaths each year. Here, we used a reverse genetics approach to examine the role of NSP4 N-glycosylation. An N-glycosylation-defective virus showed attenuated and cell-type-dependent replication in vitro. In addition, mice infected with the N-glycosylation-defective virus had less severe diarrhea than mice infected with the wild type. These results suggest that N-glycosylation affects viral replication and pathogenesis. Considering the reduced pathogenicity in vivo and the high propagation rate in MA104 cells, this glycosylation-defective virus could be an ideal live attenuated vaccine candidate.

[1,2,4]Triazolo[1,5-a]pyrimidine derivatives: Structure-activity relationship study leading to highly selective ENPP1 inhibitors.

The STING (stimulator of interferon genes) pathway is one of the pathways that regulate innate immunity, and the extracellular hydrolytic enzyme ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) has been identified as its dominant negative regulator. Since activation of the innate immune system is a promising strategy for the treatment of various infectious diseases and cancers, ENPP1 inhibitors have attracted great attention as candidate drugs. We have previously identified small-molecule ENPP1 inhibitors having a [1,2,4]triazolo[1,5-a]pyrimidine scaffold by means of chemical screening using a fluorescence probe, TG-mAMP. In this study, we evaluated the structure-activity relationships of the hit and lead compounds in detail, and succeeded in developing compounds that strongly and selectively inhibit ENPP1 not only in vitro, but also in cellular systems.

Development of an entirely plasmid-based reverse genetics system for 12-segmented double-stranded RNA viruses.

The family Reoviridae is a nonenveloped virus group with a double-stranded (ds) RNA genome comprising 9 to 12 segments. In the family Reoviridae, the genera Cardoreovirus, Phytoreovirus, Seadornavirus, Mycoreovirus, and Coltivirus contain virus species having 12-segmented dsRNA genomes. Reverse genetics systems used to generate recombinant infectious viruses are powerful tools for investigating viral gene function and for developing vaccines and therapeutic interventions. Generally, this methodology has been utilized for Reoviridae viruses such as Orthoreovirus, Orbivirus, Cypovirus, and Rotavirus, which have genomes with 10 or 11 segments, respectively. However, no reverse genetics system has been developed for Reoviridae viruses with a genome harboring 12 segments. Herein, we describe development of an entire plasmid-based reverse genetics system for Tarumizu tick virus (TarTV) (genus Coltivirus, family Reoviridae), which has a genome of 12 segments. Recombinant TarTVs were generated by transfection of 12 cloned complementary DNAs encoding the TarTV genome into baby hamster kidney cells expressing T7 RNA polymerase. Using this technology, we generated VP12 mutant viruses and demonstrated that VP12 is an N-glycosylated protein. We also generated a reporter virus expressing the HiBiT-tagged VP8 protein. This reverse genetics system will increase our understanding of not only the biology of the genus Coltivirus but also the replication machinery of the family Reoviridae.

Analysis of the relationship between spinal alignment and retrocrural space area in adult spinal deformity surgery: Potential risk factors for acute celiac artery compression syndrome.

PURPOSE: This study was designed to reveal the association between spinal parameters and RCS area in patients with adult spinal deformities treated with spinal correction surgery. We hypothesized that reduction of the retrocrural space (RCS) area is related to thoracolumbar alignment, which may cause acute celiac artery compression syndrome (ACACS). METHODS: Eighty-nine patients (age: 68.4 ± 7.6 years; sex: 7 male/82 female) with ASD treated by spinal correction surgery were enrolled. Preoperative and postoperative spinal parameters were measured, and the differences between these parameters were calculated. Postoperative T12 translation was measured and RCS area was evaluated using reconstructed computed tomography. The change of RCS area after surgery was defined as ΔRCS. Patients were divided into increased and decreased RCS groups by the ΔRCS value, and spinal parameters were compared between groups. The correlation between spinal parameters and ΔRCS was calculated. RESULTS: The patients in the decreased RCS group had greater anterior T12 translation than those in the increased RCS group (p < 0.001). T12 translation was significantly correlated with ΔRCS (ß = -0.31, p = 0.017). There were no correlations between ΔRCS and other spinal parameters. CONCLUSION: Thoracolumbar alignment was associated with RCS area. Consistent with the hypothesis, overcorrection of the thoracolumbar junction was associated with reduced RCS area and might be one risk factor for ACACS.

Long-term changes in bone mineral density following adolescent idiopathic scoliosis surgery: a minimum 34-year follow-up.

PURPOSE: To investigate longitudinal changes in bone mineral density (BMD) in middle-aged female patients who underwent spinal fusion for adolescent idiopathic scoliosis (AIS). METHODS: The study subjects were 229 female patients who were diagnosed with AIS and underwent spinal fusion between 1968 and 1988. A two-step survey study was conducted on 19 female AIS patients. BMD, Z-scores, T-scores, and the prevalence of osteoporosis and osteopenia were compared between the initial (2014-2016) and second (2022) surveys. Correlations between the annual changes in Z-scores and T-scores with radiographic parameters, body mass index (BMI), and the number of remaining mobile discs were analyzed. RESULTS: BMD decreased significantly from the initial (0.802 ± 0.120 g/cm2) to the second survey (0.631 ± 0.101 g/cm2; p < 0.001). Z-scores decreased from 0.12 ± 1.09 to - 0.14 ± 1.04, while T-scores decreased significantly from - 0.70 ± 1.07 to - 1.77 ± 1.11 (p < 0.001). The prevalence of osteopenia and osteoporosis increased significantly from 36.8% to 89.5% (p = 0.002), but the increase in osteoporosis alone was not statistically significant (5.3% to 26.3%; p = 0.180). Moderate negative correlations were found between annual changes in Z-scores and both main thoracic (MT) curve (r = - 0.539; p = 0.017) and lumbar curve (r = - 0.410; p = 0.081). The annual change in T-scores showed a moderate negative correlation with the MT curve (r = - 0.411; p = 0.081). CONCLUSION: Significant reductions in BMD and an increased prevalence of osteopenia and osteoporosis were observed in middle-aged female AIS patients who had undergone spinal fusion. The decline in Z-scores in patients with AIS suggested that there was an accelerated loss of BMD compared with the general population. Larger residual curves could pose an added osteoporosis risk. Further research is needed to understand if the onset of osteoporosis in AIS patients is attributable to the condition itself or the surgical intervention.

Efficient Selective Adsorption of SARS-CoV-2 via the Recognition of Spike Proteins Using an Affinity Spongy Monolith.

Since the outbreak of COVID-19, SARS-CoV-2, the infection has been spreading to date. The rate of false-negative result on a polymerase chain reaction (PCR) test considered the gold standard is roughly 20%. Therefore, its accuracy poses a question as well as needs improvement in the test. This study reports fabrication of a substrate of an anti-spike protein (AS)-immobilized porous material having selective adsorption toward a spike protein protruding from the surface of SARS-CoV-2. We have employed an organic polymer substrate called spongy monolith (SPM). The SPM has through-pores of about 10 µm and is adequate for flowing liquid containing virus particles. It also involves an epoxy group on the surface, enabling arbitrary proteins such as antibodies to immobilize. When antibodies of the spike protein toward receptor binding domain were immobilized, selective adsorption of the spike protein was observed. At the same time, when mixed analytes of spike proteins, lysozymes and amylases, were flowed into an AS-SPM, selective adsorption toward the spike proteins was observed. Then, SARS-CoV-2 was flowed into the BSA-SPM or AS-SPM, amounts of SARS-CoV-2 adsorption toward the AS-SPM were much larger compared to the ones toward the BSA-SPM. Furthermore, rotavirus was not adsorbed to the AS-SPM at all. These results show that the AS-SPM recognizes selectively the spike proteins of SARS-CoV-2 and may be possible applications for the purification and concentration of SARS-CoV-2.

Risk factors for vertebral bridging in residual adolescent idiopathic scoliosis with thoracolumbar/lumbar curves.

BACKGROUND: Although vertebral bridging in residual adolescent idiopathic scoliosis (AIS) can make corrective surgery more complicated, no study has investigated the risk factors. The purpose of this research was to determine risk factors for vertebral bridging in individuals with residual AIS with thoracolumbar/lumbar (TL/L) curves. METHODS: Forty-two pre-operative patients with residual AIS and TL/L curves (3 males, 39 females: age 41.9 ± 18.0 years) were divided into bridging (n = 17) and non-bridging (n = 25) groups. All patients were 20 years or older with a diagnosis of AIS in adolescence. The bridging group consisted of patients with third or more degree bridging by the Nathan classification. RESULTS: There were significant differences in age, absolute value of apical vertebral translation (AVT), C7 translation, and L3,4 tilt between groups. There was no significant difference in TL/L Cobb angle. Multivariate analyses and ROC curves demonstrated that older age was a significant risk factor for vertebral bridging (odds ratio [OR]: 1.08; 95% confidence interval: 1.02-1.14; P = 0.004), with a cutoff value of 38.0 years old. CONCLUSIONS: This study indicates that patients >38 years old are at risk for vertebral bridging in residual AIS. Because of the higher risk of vertebral bridging and other degenerative changes, residual AIS patients about 40 years of age are at a critical point for treatment strategy. Because appropriate surgical time should not be missed, regular follow-up is required even after 30 years of age, especially if the patient with residual AIS has a large TL/L curve indicated for surgery.

Associated factors and effects of coronal vertebral wedging angle in thoracic adolescent idiopathic scoliosis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) causes vertebral wedging, but associated factors and the impact of vertebral wedging are still unknown. We investigated associated factors and effects of vertebral wedging in AIS using computed tomography (CT). METHODS: Preoperative patients (n = 245) with Lenke types-1 and 2 were included. Vertebral wedging, lordosis, and rotation of the apical vertebra were measured by preoperative CT. Skeletal maturity and radiographic global alignment parameters were evaluated. Multiple regression analysis was performed on associated factors for vertebral wedging. Side-bending radiographs were evaluated using multiple regression analysis to calculate the percentage of reduction of Cobb angles to determine curve flexibility. RESULTS: The mean vertebral wedging angle was 6.8 ± 3.1°. Vertebral wedging angle was positively correlated with proximal thoracic (r = 0.40), main thoracic (r = 0.54), and thoracolumbar/lumbar curves (r = 0.38). By multiple regression, the central sacral vertical line (p = 0.039), sagittal vertical axis (p = 0.049), main thoracic curve (p = 0.008), and thoracolumbar/lumbar curve (p = 0.001) were significant factors for vertebral wedging. In traction and side-bending radiographs there were positive correlations between curve rigidity and the vertebral wedging angle (r = 0.60, r = 0.59, respectively). By multiple regression, thoracic kyphosis (p < 0.001), lumbar lordosis (p = 0.013), sacral slope (p = 0.006), vertebral wedging angle (p = 0.003), and vertebral rotation (p = 0.002) were significant factors for curve flexibility. CONCLUSIONS: Vertebral wedging angle was found to be highly correlated to coronal Cobb angle, with larger vertebral wedging indicating less flexibility.

Risk factors for celiac artery and superior mesenteric artery stenosis in preoperative lumbar and thoracolumbar spinal surgery patients.

BACKGROUND: Ischemic necrosis of the abdominal organs caused by compression of the celiac artery (CA) and superior mesenteric artery (SMA) by the median arcuate ligament (MAL) after correction surgery has been recognized as acute celiac artery compression syndrome (ACACS). Here, using contrast-enhanced computed tomographic (CT) images, we sought to determine the prevalence and degree of CA and SMA stenosis in spinal patients preoperatively, and the risk factors associated with the stenosis. METHODS: We retrospectively examined contrast-enhanced abdominal CT of 90 patients with preoperative lumbar degenerative disease, lumbar burst fracture, or adult spinal deformity. The trunks of the CA and SMA were detected using three-dimensional reconstructed CT. To investigate their degree of stenosis, we determined the ratio of the narrowest diameter of the stenotic segment to the distal normal lumen's diameter. Patients with a degree of stenosis ≥35% were defined as being in the group with stenosis and the remainder as in the group without. To determine the risk factors for stenosis of these arteries, the relationship between the stenosis and CA and SMA calcification or the median arcuate ligament (MAL) crossing the proximal portion of the celiac axis (MAL overlap) was also investigated. RESULTS: The average degree of stenosis of the CA trunk was 12.1% ± 13.9% and that for the SMA trunk was 8.5% ± 8.8%. There were 8 patients (8.9%) in the group with CA stenosis and 2 patients (2.2%) in the group with SMA stenosis. The number of patients in the group with CA stenosis was significantly greater than the number with MAL overlap or CA calcification (P < 0.05). DISCUSSION: The prevalence of CA or SMA stenosis was 11.2% of preoperative patients due to undergo thoracolumbar fusion surgery. Calcifications of the CA trunk and MAL overlap are risk factors for CA stenosis.

Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells.

Quercetin, a flavonoid compound widely distributed in many plants, is known to have potent antitumor effects on several cancer cells. Our previous study revealed that the acetylation of quercetin enhanced its antitumor effect. However, the mechanisms remain unknown. This study aimed to elucidate the bioavailability of acylated quercetin in the HepG2 cell model based on its antitumor effect. The positions of quercetin 3,7,3',4'-OH were acetylated as 3,7,3',4'-O-tetraacetylquercetin (4Ac-Q). The inhibitory effect of 4Ac-Q on HepG2 cell proliferation was assessed by measuring cell viability. The apoptosis was characterized by apoptotic proteins and mitochondrial membrane potential shifts, as well as mitochondrial reactive oxygen species (ROS) levels. The bioavailability of 4Ac-Q was analyzed by measuring the uptake and metabolites in HepG2 cells with high performance liquid chromatography (HPLC)-photodiode array detector (PDA) and-ultraviolet/visible detector (UV/Vis). The results revealed that 4Ac-Q enhanced the inhibitory effect on HepG2 cell proliferation and induced its apoptosis significantly higher than quercetin. Protein array analysis of apoptosis-related protein indicated that 4Ac-Q increased the activation or expression of pro-apoptotic proteins, including caspase-3, -9, as well as second mitochondria-derived activator of caspases (SMAC), and suppressed the expression of apoptosis inhibiting proteins such as cellular inhibitor of apoptosis (cIAP)-1, -2, Livin, Survivin, and X-linked inhibitor of apoptosis (XIAP). Furthermore, 4Ac-Q stimulated mitochondrial cytochrome c release into the cytosol by enhancing ROS level and depolarizing the mitochondrial membrane. Finally, the analysis of uptake and metabolites of 4Ac-Q in HpG2 cells with HPLC-PDA and -UV/Vis revealed that 4Ac-Q was metabolized to quercetin and several different acetylated quercetins which caused 2.5-fold higher quercetin present in HepG2 cells than parent quercetin. These data demonstrated that acetylation of the quercetin hydroxyl group significantly increased its intracellular absorption. Taken together, our findings provide the first evidence that acetyl modification of quercetin not only substantially augments the intracellular absorption of quercetin but also bolsters its metabolic stability to elongate its intracellular persistence. Therefore, acetylation could serve as a strategic approach to enhance the ability of quercetin and analogous flavonoids to suppress cancer cell proliferation.

Zoonotic Infection with Oz Virus, a Novel Thogotovirus.

Oz virus is a novel thogotovirus isolated from ticks that causes lethal infection in mice. We conducted serosurveillance of Oz virus infection among humans and wild mammals in Japan using virus-neutralization tests and ELISAs. Results showed that Oz virus may be naturally infecting humans and other mammalian hosts.

A reverse genetics system for human rotavirus G2P[4].

Rotaviruses (RVs) are an important cause of acute gastroenteritis in young children. Recently, versatile plasmid-based reverse genetics systems were developed for several human RV genotypes; however, these systems have not been developed for all commonly circulating human RV genotypes. In this study, we established a reverse genetics system for G2P[4] human RV strain HN126. Nucleotide sequence analysis, including that of the terminal ends of the viral double-stranded RNA genome, revealed that HN126 possessed a DS-1-like genotype constellation. Eleven plasmids, each encoding 11 gene segments of the RV genome, and expression plasmids encoding vaccinia virus RNA capping enzyme (D1R and D12L), Nelson Bay orthoreovirus FAST, and NSP2 and NSP5 of HN126, were transfected into BHK-T7 cells, and recombinant strain HN126 was generated. Using HN126 or simian RV strain SA11 as backbone viruses, reassortant RVs carrying the outer and intermediate capsid proteins (VP4, VP7 and VP6) of HN126 and/or SA11 (in various combinations) were generated. Viral replication analysis of the single, double and triple reassortant viruses suggested that homologous combination of the VP4 and VP7 proteins contributed to efficient virus infectivity and interaction between other viral or cellular proteins. Further studies of reassortant viruses between simian and other human RV strains will contribute to developing an appropriate model for human RV research, as well as suitable backbone viruses for generation of recombinant vaccine candidates.

Prevalence of pleural injury in an extrapleural approach to adolescent idiopathic scoliosis and association of pleural injury with postoperative respiratory function.

BACKGROUND: The prevalence of pleural injury during surgery for adolescent idiopathic scoliosis using an extrapleural approach and the association of pleural injury with postoperative pulmonary function remain unclear. We sought to determine the prevalence of pleural injury associated with an extrapleural approach to adolescent idiopathic scoliosis, and to determine any difference in respiratory function between patients with or without pleural injury. METHODS: Data from consecutive patients with scoliosis of the thoracolumbar/lumbar spine who underwent anterior spinal fusion using an extrapleural approach were assessed in this retrospective study. We had diagnosed and treated pleural injury according to our algorithm. Pre- and postoperative values of pulmonary function tests and postoperative change rates were compared between patients with and without pleural injury. FVC, %FVC, FEV1.0, and FEV1.0% were evaluated from pulmonary function tests. RESULTS: We included data from 51 patients with adolescent idiopathic scoliosis (45 female and 6 male) with a mean age of 17.2 ± 3.5 years in this retrospective study. The group with pleural injury comprised 31 patients and the group without 20. Therefore, the prevalence of pleural injury during an extrapleural approach was 61%. We found no significant differences in preoperative FVC, %FVC, FEV1.0, and FEV1.0% between the groups. We found no significant differences in FVC, %FVC, FEV1.0, and FEV1.0% between the groups at 3 months or 1 year postoperatively. Furthermore, we found no significant differences in the postoperative change ratio of FVC, %FVC, FEV1.0, and FEV1.0% between the groups. CONCLUSION: The prevalence of pleural injury associated with an extrapleural approach to scoliosis was 61%. Pleural injury was not associated with a decrease in postoperative pulmonary function in patients with scoliosis treated using an extrapleural approach.

Efficacy of lateral lumbar interbody fusion combined with posterior spinal fusion compared with three-column osteotomy for adult spinal deformity with severe lumbar sagittal deformity.

PURPOSE: The clinical and radiological results of adult spinal deformity (ASD) patients with a severe lumbar sagittal deformity undergoing multilevel lateral lumbar interbody fusion (LLIF) + posterior spinal fusion (PSF) were compared to patients undergoing three-column osteotomy (3CO). METHODS: We defined severe lumbar sagittal deformity as fulcrum backward bending (FBB) pelvic incidence minus lumbar lordosis (PI-LL) ≧ 20 degrees. A total of twenty-five patients with an ASD were enrolled between 2013 and 2018. Fifteen patients were in the LLIF + PSF group, and ten patients were in the 3CO group. We evaluated patient demographics, clinical outcomes, and radiographic parameters such as the Cobb angle and spinopelvic parameters from standing X-ray films in each group. RESULTS: The LLIF + PSF group had a significantly shorter follow-up time than the 3CO group. Postoperatively, the LLIF + PSF group had significantly lower PI-LL and a shorter sagittal vertical axis than the 3CO group. Postoperative PI-LL changes in the LLIF + PSF group were significantly smaller than those in the 3CO group. There were no differences in other patient demographics, radiographic parameters, or clinical outcomes between the groups. CONCLUSION: Multilevel LLIF + PSF improved the PI-LL and SVA more than did 3CO for ASD patients with severe lumbar sagittal deformity. This indicated that the multilevel LLIF with open PSF can provide good clinical outcomes even in cases with severe lumbar sagittal deformity such as large FBB PI-LL in which 3CO techniques usually are needed.

Histopathological Characterization of Cases of Spontaneous Fatal Feline Severe Fever with Thrombocytopenia Syndrome, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tickborne infectious disease caused by SFTS virus (SFTSV). We report 7 cases of spontaneous fatal SFTS in felines. Necropsies revealed characteristic lesions, including necrotizing lymphadenitis in 5 cases and necrotizing splenitis and SFTSV-positive blastic lymphocytes in all cases. We detected hemorrhagic lesions in the gastrointestinal tract in 6 cases and lungs in 3 cases, suggesting a more severe clinical course of SFTS in felids than in humans. We noted necrotic or ulcerative foci in the gastrointestinal tract in 3 cases, the lung in 2 cases, and the liver in 4 cases. We clarified that blastic lymphocytes are predominant targets of SFTSV and involved in induction of necrotic foci. We also found that thymic epithelial cells were additional targets of SFTSV. These results provide insights for diagnosing feline SFTS during pathological examination and demonstrate the similarity of feline and human SFTS cases.

What factor induces stress in patients with AIS under brace treatment? Analysis of a specific factor using exploratory factor analysis.

BACKGROUND: Stress from brace treatment in patients with adolescent idiopathic scoliosis (AIS) can deteriorate their quality of life. A Japanese version of the Bad Sobernheim Stress Questionnaire-Brace (JBSSQ-brace) was developed to assess the stress from brace treatment for Japanese patients with AIS. However, the specific factors causing stress under brace treatment have remained unknown. METHOD: We enrolled 69 consecutive Japanese patients with AIS. Stress from brace treatment was assessed by JBSSQ-brace and Scoliosis Research Society-22 (SRS-22) instruments. The correlations of JBSSQ-brace with SRS-22 score, patient demographics and Cobb angle were analyzed by Spearman's rank correlation. Exploratory factor analysis was used to determine the psychological factor causing stress from brace treatment. RESULTS: JBSSQ-brace score was correlated with total score of SRS-22, self-image and mental health domain, but not age, degree of curvature, or other domains of the SRS-22. Factor analysis detected one underlying factor, which was more related to Questions 4 or 5 with the factor loadings of 0.8 than Questions 1 or 6 with loadings of 0.65. CONCLUSION: Stress from brace treatment was not associated with age, spinal curve severity, pain, or satisfaction of treatment. Exploratory factor analysis suggested "anxious feeling about how we are perceived by others" induces the stress from brace treatment in Japanese patients with AIS.

Anchor type at upper instrumented vertebra and postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis.

PURPOSE: To clarify the impact of anchor type at upper instrumented vertebra (UIV) on postoperative shoulder imbalance in patients with Lenke type 1 adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion. METHODS: Subjects were 81 patients with Lenke type 1 AIS who underwent posterior spinal fusion between 2004 and 2013. Twenty-five patients agreed to participate in the study. We divided the patients into two groups: Hook group (15 patients with hooks at UIV who underwent surgery between 2004 and 2011) and PS group (ten patients with pedicle screws at UIV who underwent surgery between 2012 and 2013). To evaluate shoulder balance, first thoracic vertebra tilt angle (T1 tilt), clavicle angle (CA), and radiographic shoulder height (RSH) were measured. RESULTS: There were no significant differences in preoperative T1 tilt, CA, or RSH between the both groups. The postoperative 1-week, 2-year, and most recently observed T1 tilts were significantly smaller in the Hook group than in the PS group. There were no significant differences in postoperative 1-week, 2-year, and most recently observed CAs between the two groups. Although there were no significant differences in 1-week postoperative RSH between the groups, the 2-year postoperative RSH was significantly smaller in the Hook group than in the PS group. The most recently observed RSH tended to be smaller in the Hook group than in the PS group, but the difference was not significant. CONCLUSIONS: In the PS group, poor shoulder balance remained over the long term. The hooks at UIV adjusted postoperative shoulder balance.