Age-adjusted 5-factor modified frailty index as a valuable tool for patient selection in bilateral simultaneous total knee arthroplasty.

Although bilateral simultaneous total knee arthroplasty (BSTKA) is an effective treatment for bilateral knee osteoarthritis, safety concerns and lack of precise patient selection criteria persist. The purpose of this retrospective study was to determine the complication rate and the role of frailty in patient selection for BSTKA. We analyzed data from 434 patients who underwent BSTKA between February 2012 and January 2021, examining demographic factors and preoperative blood test results. Complications occurred in 77 patients (18%), with anemia requiring transfusion being the most common (26 patients, 5.9%). In the univariate analysis, age ≥ 75 years, age-adjusted Charlson Comorbidity Index ≥ 5, age-adjusted 5-factor modified Frailty Index (aamFI-5) ≥ 3, hemoglobin ≤ 11.0 g/dL, albumin ≤ 3.5 g/dL, estimated glomerular filtration rate < 45 ml/dl/1.73 m2, and D-dimer ≥ 2.0 µg/mL contributed to postoperative complications (p < 0.05). Multivariate analysis identified aamFI-5 ≥ 3 as an independent risk factor (p = 0.002). Our findings underscore the practical utility of aamFI-5 in predicting complications after BSTKA, providing valuable guidance to surgeons in the selection of BSTKA candidates and ultimately improving clinical outcomes.

Total talar replacement for metastatic pulmonary adenocarcinoma of the talus: A case report.

Talar metastases from malignant tumors are rare and poorly documented. Treatment requires gradual relief of pain and preservation of function, with a choice between palliative measures and surgery. This case indicates that total talar replacement is an effective intervention for localized talar metastases and highlights the importance of early intervention. A 48-year-old man was diagnosed with a pathologic talar fracture due to talar metastases was observed after 8 years of chemotherapy following a diagnosis of lung adenocarcinoma. Despite radiotherapy, the patient's activities of daily living (ADLs) deteriorated due to pain on walking, prompting a request for surgical intervention. Total talar replacement was performed, allowing the patient to begin full weight-bearing ambulation 2 weeks post-operatively. Total talar replacement appears to be an effective treatment for localized talar metastases and should be performed as early as possible.

Verification of Qfix Encompass™ couch modeling using the Acuros XB algorithm and HypeArc™ using a high-spatial-resolution two-dimensional diode array.

We modeled the Qfix Encompass™ immobilization system and further verified the calculated dose distribution of the AcurosXB (AXB) dose calculation algorithm using SRS MapCHECKⓇ (SRSMC) in the HyperArc™ (HA) clinical plan. An Encompass system with a StereoPHAN™ QA phantom was scanned by SOMATOM go.Sim and imported to an Eclipse™ treatment planning system to create a treatment plan for Encompass modeling. The Encompass modeling was performed in the StereoPHAN with a pinpoint ion chamber for 6 MV and 6 MV flattening filter free (6 MV FFF), and 2 × 2 cm2, 4 × 4 cm2, and 6 × 6 cm2 irradiation field sizes. The dose calculation algorithm used was AXB ver. 15.5 with a 1.0 mm calculation grid size. The Hounsfield unit (HU) values of the Encompass modeling were set to 400, -100, -200, and -300 for Encompass, and -400, -600, -700, and -800 for the Encompass base. We evaluated the dose distribution after Encompass modeling by SRSMC using gamma analysis in 12 patients. We adopted HU values of -200 for Encompass, -800 for Encompass base for 6 MV, and -200 for Encompass and -700 for Encompass. Base for 6 MV FFF was adopted as the HU values for the Encompass modeling based on the measurement results. The proposed Encompass modeling resulted in a mean pass rate evaluation >98% for both 6 MV and 6 MV FFF when the 1%/1 mm criterion was used, demonstrating that the proposed HU value can be adopted to calculate more accurate dose distributions.

Digital Transformation Will Change Medical Education and Rehabilitation in Spine Surgery.

The concept of minimally invasive spine therapy (MIST) has been proposed as a treatment strategy to reduce the need for overall patient care, including not only minimally invasive spine surgery (MISS) but also conservative treatment and rehabilitation. To maximize the effectiveness of patient care in spine surgery, the educational needs of medical students, residents, and patient rehabilitation can be enhanced by digital transformation (DX), including virtual reality (VR), augmented reality (AR), mixed reality (MR), and extended reality (XR), three-dimensional (3D) medical images and holograms; wearable sensors, high-performance video cameras, fifth-generation wireless system (5G) and wireless fidelity (Wi-Fi), artificial intelligence, and head-mounted displays (HMDs). Furthermore, to comply with the guidelines for social distancing due to the unexpected COVID-19 pandemic, the use of DX to maintain healthcare and education is becoming more innovative than ever before. In medical education, with the evolution of science and technology, it has become mandatory to provide a highly interactive educational environment and experience using DX technology for residents and medical students, known as digital natives. This study describes an approach to pre- and intraoperative medical education and postoperative rehabilitation using DX in the field of spine surgery that was implemented during the COVID-19 pandemic and will be utilized thereafter.

Effect of Genetic Polymorphisms of Human SLC22A3 in the 5'-flanking Region on OCT3 Expression and Sebum Levels in Human Skin.

BACKGROUND: Human organic cation transporter 3 (OCT3,SLC22A3) mediates the uptake of many important endogenous substances and basic drugs, and has been identified as one of the transporters that are highly expressed in human skin. However, the mechanisms responsible for variability in mRNA expression, and the role of SLC22A3 in human skin is not clear. OBJECTIVE: We examined the effects of the single nucleotide polymorphisms ofSLC22A3 on the variability in SLC22A3 expression and sebum levels in humans. METHODS: Immunostaining of OCT3 in human skin was performed. We analyzed the association of promoter variants with the SLC22A3 mRNA expression levels in human skins. Luciferase, knockdown, chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay were employed to investigate transcriptional regulation of SLC22A3 expression. Effects of the identified variant on sebum levels were evaluated in healthy volunteers. RESULTS: Immunohistochemistry revealed marked expressions of OCT3 in the basal epidermis, sebaceous glands, hair follicles, and sweat glands of human skin. SLC22A3 mRNA levels were significantly lower in skin samples with homozygotes for -1603A/A than in those for -1603 G/G. The analysis of p53 binding to -1603 G > A in the promoter ofSLC22A3 suggested that -1603 G > A down-regulates SLC22A3 gene expression by decreased p53 binding in the vicinity of the -1603 site. In humans, squalene levels in samples from the back at the baseline were significantly lower in homozygotes for -1603A/A than in those for -1603 G/G. CONCLUSION: These results suggest that the genetic variant contributes to the variability of expression and activities of OCT3 in human skin.

Traumatic boutonniere deformity of the second toe caused by sumo wrestling: A case report.

INTRODUCTION: Traumatic boutonniere deformities of the fingers are well documented unlike those of the lesser toes. With few existing reports on boutonniere deformities of the lesser toes, the related pathology and treatment guidelines remain unclear. PRESENTATION OF CASE: We present a case of traumatic boutonniere deformity of the second toe caused by sumo wrestling in a 23-year-old man. A flexion deformity of the proximal interphalangeal joint and hyperextension of the distal interphalangeal joint of the right second toe were observed, including a torn central slip and plantarly displaced lateral bands during surgery. Surgical repair of the extensor mechanism and temporary pinning led to good clinical results. DISCUSSION: Acute traumatic boutonniere deformity of the interphalangeal joint of the lesser toe is very rare. The mechanism of boutonniere deformity in this case is thought to be due to forced passive flexion exerted on an actively extended PIP joint, which is similar to that seen in fingers. CONCLUSION: We describe the pathophysiology of a case of boutonniere deformity of the lesser toe and suggest the effectiveness of surgical treatment.

Evaluation of D-isomer of 18F-FBPA for oncology PET focusing on the differentiation of glioma and inflammation.

OBJECTIVES: L-4-borono-2-18F-fluoro-phenylalanine (L-[18F]FBPA), a substrate of L-type amino acid transporter 1 (LAT1), is a tumor-specific probe used in positron emission tomography (PET). On the other hand, it has not been examined whether another isomer D-[18F]FBPA accumulates specifically in the tumor. Here, we compared the accumulation of D-[18F]FBPA in C6 glioma and inflammation to evaluate the performance of D-[18F]FBPA as a tumor-specific probe. METHODS: HEK293-LAT1 and HEK293-LAT2 cells were tested for [14C]-leucine or [14C]-alanine transport, and IC50 values of L- and D-FBPA were evaluated in both cell types. PET was conducted in rat xenograft model of C6 glioma with LAT1 expression and model of turpentine oil-induced subcutaneous inflammation (n=10 for both models). The concentrations of D-[18F]FBPA were compared between glioma and inflammatory lesion using standardized uptake value (SUV). RESULTS: In contrast to L-FBPA, which inhibited substrate uptake in both HEK293-LAT1 and -LAT2 cells, D-FBPA showed no inhibitory effect on both cells, suggesting low transporter selectivity of D-[18F]FBPA against LAT1 and LAT2. Static PET analysis showed low accumulation of D-[18F]FBPA in C6 glioma and inflammatory lesion (SUVmax=0.80±0.16, 0.56±0.09, respectively). Although there was a statistical difference in SUVmax between these tissues, it was difficult to distinguish glioma from inflammation on the PET image due to its low uptake level. Therefore, it was suggested that D-[18F]FBPA is not a suitable tumor-specific probe for oncology PET in contrast to L-[18F]FBPA. CONCLUSION: This study demonstrated that D-[18F]FBPA is not a LAT1-specific PET probe and shows low uptake in C6 glioma, indicating its unsuitability as a tumor diagnosis PET probe.

Interindividual Differences in the Expression of ATP-Binding Cassette and Solute Carrier Family Transporters in Human Skin: DNA Methylation Regulates Transcriptional Activity of the Human ABCC3 Gene.

The identification of drug transporters expressed in human skin and interindividual differences in gene expression is important for understanding the role of drug transporters in human skin. In the present study, we evaluated the expression of ATP-binding cassette (ABC) and solute carrier (SLC) transporters using human skin tissues. In skin samples, ABCC3 was expressed at the highest levels, followed by SLCO3A1, SLC22A3, SLC16A7, ABCA2, ABCC1, and SLCO2B1. Among the quantitated transporters, ABCC3 accounted for 20.0% of the total mean transporter mRNA content. The expression of ABCC3 mRNA showed large interindividual variability (9.5-fold). None of the single nucleotide polymorphisms tested (-1767G>A, -1328G>A, -1213C>G, -897delC, -260T>A, and -211C>T) in the promoter region of the ABCC3 gene showed a significant change in ABCC3 mRNA levels. ABCC3 expression levels negatively correlated with the methylation status of the CpG island (CGI) located approximately 10 kilobase pairs upstream of ABCC3 (Rs: -0.323, P < 0.05). The reporter gene assay revealed a significant increase in transcriptional activity in the presence of CGI. ABCC3 mRNA was upregulated in HaCaT cells by the demethylating agent 5-aza-2'-deoxycytidine. Furthermore, the deletion of the region surrounding CGI using the clustered regularly interspaced short palindromic repeat/Cas9 system resulted in significantly lower ABCC3 mRNA levels than those in control clones in HaCaT cells. Herein, we demonstrated large interindividual differences in the expression of drug transporters in human skin. CGI may function as an enhancer of the transcription of ABCC3, and methylation levels in CGI contribute to the variability of ABCC3 expression in human skin.

Effectiveness of Helicobacter pylori eradication in the prevention of primary gastric cancer in healthy asymptomatic people: A systematic review and meta-analysis comparing risk ratio with risk difference.

BACKGROUND: Helicobacter pylori infection is strongly associated with gastric cancer occurrence. However, it is unclear whether eradication therapy reduces the risk of gastric cancer occurrence. We evaluated whether H. pylori eradication reduces the risk of primary gastric cancer by using both risk ratio (RR) and risk difference (RD). METHODS: Searches of PubMed, EMBASE, Google scholar, the Cochrane Library, and the Japan Medical Abstracts Society as well as those registered in databases of the Cochrane Central Register of Controlled Trials, metaRegister of Controlled Trials, ClinicalTrials.gov, controlled-trials.com, UMIN-CTR, JMACCT-CTR, and JAPIC-CTI between January 1965 and March 2017, supplemented with manual screening. Randomized controlled trials (RCTs) in which eradication therapy were implemented for the interventional group but not for the control group, and assessed the subsequent occurrence of primary gastric cancer as the main outcome. Two authors independently reviewed articles and extracted data. Integrated results for all data were presented as RR and RD. RESULTS: Seven studies met inclusion criteria. The reductions in risk of primary gastric cancer occurrence in terms of overall RR and RD were 0.67 (95% CI: 0.48 to 0.95) and -0.00 ([95% CI: -0.01 to 0.00]; number needed to treat: 125.5 [95% CI: 70.0 to 800.9]), respectively. CONCLUSIONS: The effectiveness of H. pylori eradication therapy in suppressing the occurrence of primary gastric cancer was significant and comparable to that of previous studies in terms of the estimated RR. However, the estimated RD was slight and not statistically significant.

Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery.

Influenza A virus (IAV) membrane proteins hemagglutinin (HA) and neuraminidase (NA) are determinants of virus infectivity, transmissibility, pathogenicity, host specificity, and major antigenicity. HA binds to a virus receptor, a sialoglycoprotein or sialoglycolipid, on the host cell and mediates virus attachment to the cell surface. The hydrolytic enzyme NA cleaves sialic acid from viral receptors and accelerates the release of progeny virus from host cells. In this study, we identified a novel function of HA and NA as machinery for viral motility. HAs exchanged binding partner receptors iteratively, generating virus movement on a receptor-coated glass surface instead of a cell surface. The virus movement was also dependent on NA. Virus movement mediated by HA and NA resulted in a three to four-fold increase in virus internalisation by cultured cells. We concluded that cooperation of HA and NA moves IAV particles on a cell surface and enhances virus infection of host cells.

Reduced induction of anti-PF4/heparin antibody in RA patients after total knee arthroplasty.

BACKGROUND: Heparin-induced thrombocytopenia is caused by antibodies (Abs) specific to platelet factor 4 (PF4)/heparin complexes. In this study, we evaluated the rates of seroconversion of anti-PF4/heparin Ab between patients with rheumatoid arthritis (RA) and with osteoarthritis (OA) who underwent total knee arthroplasty. METHODS: The subjects of this randomized controlled trial were 124 patients who underwent total knee arthroplasty (TKA) and received edoxaban with or without a foot pump as thromboprophylaxis. We measured anti-PF4/heparin Abs before and 10 days after surgery, as well as preoperative PF4, using commercially available ELISAs. We also used the database of J-PSVT, a hospital-based, prospective cohort study designed to document the effectiveness of thromboprophylactic agents during arthroplasty. RESULTS: The rates of seroconversion to anti-PF4/heparin Ab were lower in RA patients (4.0 %) than in OA patients (25.5 %). The anti-PF4/heparin IgG optical density (OD) values did not differ before and after surgery in RA patients. In contrast, there was a significant increase in anti-PF4/heparin IgG OD values in OA patients after TKA. In the J-PSVT data, the postoperative seroconversion rates of anti-PF4/heparin Ab were lower in RA patients (10.4 %) than in OA patients (21.8 %) who received fondaparinux. The titers of anti-CCP Ab were significantly lower in RA patients with postoperative ant-PF4/heparin Ab compared with those without postoperative ant-PF4/heparin Ab There was no significant difference in preoperative PF4 levels between RA patients and OA patients. The heparin-binding affinity of the circulating PF4 was similar between RA patients and OA patients; however, the IgG fractions isolated from the sera of RA patients contained PF4 more frequently (69.2 %) than those from OA patients (10.2 %). CONCLUSIONS: Our results showed a reduced likelihood of postoperative anti-PF/heparin Ab production in RA patients compared with OA patients. This suggests that the mechanisms underlying the anti-PF4 immune response in RA patients differ from the mechanisms of the anti-PF4/heparin immune response seen in OA patients after joint replacement. TRIAL REGISTRATION: ISRCTN 18090286. Registered 8 July 2016.

Selenium metabolism and excretion in mice after injection of (82)Se-enriched selenomethionine.

The organic Se compounds (particularly selenomethionine [SeMet]) in plants and yeasts are very effective chemoprotectants for mammalian cancer. To characterize the dynamics of selenomethionine utilization pathways, we intravenously injected (82)Se-enriched SeMet into mice under different nutritional states (Se-adequate and Se-deficient mice) and then measured their endogenous and exogenous (82)Se levels. Furthermore, we quantified Se compounds and selenoproteins in liver, kidneys, plasma, and urine. The average recoveries of exogenous (82)Se from solid tissues, urine, and feces were 81% for Se-adequate mice and 84% for Se-deficient mice. Exogenous (82)Se was distributed in the hepatic and renal cytosols as cellular glutathione peroxidase (cGPx), selenosugar, and SeMet within 1 h after injection. Synthesis of cGPx was maintained until 72 h after injection, regardless of the Se nutritional status. Whereas plasma levels of exogenous (82)Se as selenoprotein P (Sel-P) peaked at 6 h after injection, those of Se-containing albumin (SeAlb), extracellular GPx, and SeMet peaked at 1 h after injection. These results suggest three Se transport pathways in mice injected with SeMet: SeAlb (within 1 h after injection); SeMet (from 1 to 72 h after injection); and Sel-P (from 6 to 72 h after injection). The amount of Sel-P in Se-deficient mice was 1.5 times that of Se-adequate mice, and this increase was much larger than Se-containing compounds other than Sel-P. Our results indicate that Sel-P has an important role in Se transport when the nutritional supply of Se is insufficient.

The role of M cells of human nasopharyngeal lymphoid tissue in influenza virus sampling.

Little is known about the role of the M cells of human nasopharyngeal lymphoid tissue in the sampling of viruses that cause respiratory infections. To clarify whether M cells could function as a gateway for influenza virus into human nasopharyngeal lymphoid tissue, excised adenoid tissue was incubated in media containing influenza A virus for 30, 60, and 90 min, respectively. Transmission electron microscopic observation revealed that many influenza viruses adhered to M cell surfaces and were taken up into the cytoplasmic vesicles of M cells after 30 min incubation; the viruses had been transported into enfolded lymphoid cells after 60 min incubation. By staining M cells with Sambucus nigra lectin, which specifically recognizes the NeuAcalpha2,6 Gal linkage of sialoprotein, it was also found that abundant receptors for the human influenza virus are present on the M cell surface. Our findings indicated that M cells of human nasopharyngeal tonsils function as a major port for influenza A virus entry and that the virus could be efficiently transferred to enfolded macrophages and lymphoid cells by M cells. The transport of influenza viruses to lymphoid cells by M cells may promote antigen delivery to the immune system, and these findings may be important for systemic delivery of those influenza viruses that have the capacity to productively infect cells outside of the respiratory tract.

Fatty acids on the A/USSR/77 influenza virus hemagglutinin facilitate the transition from hemifusion to fusion pore formation.

Influenza virus hemagglutinin (HA) has three highly conserved acylation sites close to the carboxyl terminus of the HA2 subunit, one in the transmembrane domain and two in the cytoplasmic domain. Each site is modified by palmitic acid through a thioester linkage to cysteine. To elucidate the biological significance of HA acylation, the acylation sites of HA of influenza virus strain A/USSR/77 (H1N1) were changed by site-directed mutagenesis, and the membrane fusion activity of mutant HAs lacking the acylation site(s) was examined quantitatively using transfer assays of lipid (R18) and aqueous (calcein) dyes. Lipid mixing, so-called hemifusion, activity was not affected by deacylation, whereas transfer of aqueous dye, so-called fusion pore formation, was dramatically restricted. When the fusion reaction was induced by a lower pH than the optimal one, calcein transfer with the mutant HAs was improved, but simultaneously a considerable calcein leakage into the medium was observed. From these results, we conclude that the palmitic acids on the H1 subtype HA facilitate the transition from hemifusion to fusion pore formation.