Preoperative Arithmetic Hip-Knee-Ankle Angle as a Predictor of Postoperative Leg Alignment in Medial Oxford Unicompartmental Knee Arthroplasty.

Introduction This study aimed to evaluate whether the arithmetic hip-knee-ankle angle (aHKA) can be used to predict the postoperative HKA. Methods This study included 248 knees in 166 patients who underwent Oxford unicompartmental knee arthroplasty (UKA) between February 2021 and November 2022. Through preoperative and postoperative long-leg radiography, the medial proximal tibial angle (MPTA) and the lateral distal femoral angle (LDFA) were expressed as the deviation from the perpendicular line to the mechanical axes, and the mechanical HKA (mHKA) was defined as the angle between the femoral and tibial mechanical axes. Using the MPTA and LDFA, the arithmetic HKA (aHKA; MPTA + LDFA) and the joint line obliquity (JLO; MPTA - LDFA) were calculated, and the preoperative and postoperative values were compared. Results The preoperative aHKA and the postoperative mHKA values were similar (-0.38° ± 2.96°) and significantly smaller than the difference between the preoperative and postoperative mHKAs (4.58° ± 3.60°, P < 0.05). Meanwhile, the MPTA tended to be varus, and the LDFA tended to be valgus. Eventually, the JLO inclined more medially from -6.33° ± 3.42° preoperatively to -8.97° ± 3.92° postoperatively, representing a significant difference (P < 0.05). Conclusion The preoperative aHKA was similar to the postoperative mHKA. Therefore, it can be regarded as a predictor of postoperative leg alignment after Oxford UKA. Meanwhile, there was a medial incline of the joint line. Further investigation is required to evaluate the effect of such a joint line alteration.

Prediction of postoperative range of motion after mobile-bearing medial unicompartmental knee arthroplasty from the preoperative range of motion and other preoperative factors.

BACKGROUND: Postoperative flexion after unicompartmental knee arthroplasty might be predicted from the preoperative range of motion and other preoperative factors, but this has not been sufficiently investigated. METHODS: Between 2013 and 2017, 198 patients (198 knees) underwent unilateral knee arthroplasty with medial mobile-bearing unicompartmental knee arthroplasty. Range of motion was measured preoperatively and at the time of final follow-up. To investigate the accuracy of the prediction of preoperative to postoperative gain or loss of the flexion angle, we performed receiver operating characteristic analysis. Logistic regression analysis was used to evaluate other predictive factors. RESULTS: Change in flexion angle was significantly strongly and negatively correlated with the preoperative flexion angle (R= -0.688, 95%CI: -0.755, -0.607, P< 0.001). Preoperative flexion angle was suggested to be a significant predictor of gain or loss of the flexion angle with the area under the curve of 0.781; ,the cut-off value calculated using the Youden index was 140°. Logistic regression analysis showed that in addition to the preoperative flexion angle of the operated side, the postoperative flexion range was significantly affected by the patient's height and by the preoperative flexion angle of the contralateral knee. CONCLUSION: If the preoperative flexion angle in Oxford mobile-bearing medial unicompartmental knee arthroplasty is < 140°, the postoperative flexion angle may be improved; if it exceeds 140°, the postoperative flexion angle may worsen. This predictive ability is further improved by consideration of the patient's height and the range of motion on the contralateral side.

Tibial Lateral Condyle Fracture After Cementless Oxford Unicompartmental Knee Arthroplasty (UKA): A Report of Four Cases.

Cementless unicompartmental knee arthroplasty (UKA) has a lower rate of radiolucency in postoperative follow-up than cemented UKA. However, the rate of tibial plateau fracture, one of the complications, has been reported to be higher in cementless UKA than in cemented UKA. We report four cases of postoperative tibial lateral condyle fractures after cementless Oxford UKA. Four patients underwent cementless Oxford UKA. Immediate postoperative radiography and CT showed no fracture lines. At five to six weeks postoperatively, MRI showed a fracture line from the intersection of the longitudinal and transverse tibial osteotomies through the lateral pinhole to the end of the lateral tibial diaphysis. At three months, bone union was observed without surgical treatments. Lateral tibial fracture after cementless Oxford UKA has a good clinical course without the need for surgical intervention. Medial fractures should thus be more actively prevented. MRI is useful for less symptomatic tibial lateral condyle fractures.

Caliper-Based Restricted Kinematic Alignment Total Knee Arthroplasty.

Restricted kinematic alignment total knee arthroplasty (rKA-TKA) is a reasonable selection for avoiding an extreme alignment that has been conceded to induce implant failure. However, computer-aided devices (CAS), such as navigation, robotics, and patient-specific instrumentation, are necessary to perform rKA-TKA. This paper reports on the surgical technique of kinematic alignment total knee arthroplasty (KA-TKA) using mechanical instruments. The lateral distal femoral angle (LDFA) and the medial proximal tibial angle (MPTA) are measured from preoperative long radiographs or CT of the lower limb, and the arithmetic hip-knee-ankle angle (aHKA) is calculated from the MPTA - LDFA. The predefined restriction boundaries are used to determine the osteotomy angle. In our practice, the LDFA is 85° to 93°, the MPTA is 85° to 90°, and the aHKA is 5° varus to 3° valgus. If correction of the femoral osteotomy is required, this can be achieved by changing the thickness of the paddle set on the distal articular surface or by adjusting the angle of the variable angle femoral cutting guide. For the tibia, the distal end of the extramedullary rod, with the proximal part placed in the center of the knee joint, should be adjusted so that it does not exceed the lateral malleolus. This limits the medial tilt of the osteotomy plane to within 5.5°. These techniques allow restricted KA to be performed with existing mechanical instruments without using CAS.

The nascent polypeptide-associated complex subunit Egd1 is required for efficient selective mitochondrial degradation in budding yeast.

Selective degradation of dysfunctional or excess mitochondria is a fundamental process crucial for cell homeostasis in almost all eukaryotes. This process relies on autophagy, an intracellular self-eating system conserved from yeast to humans and is thus called mitophagy. Detailed mechanisms of mitophagy remain to be fully understood. Here we show that mitochondrial degradation in budding yeast, which requires the pro-mitophagic protein Atg32, is strongly reduced in cells lacking Egd1, a beta subunit of the nascent polypeptide-associated complex acting in cytosolic ribosome attachment and protein targeting to mitochondria. By contrast, loss of the sole alpha subunit Egd2 or the beta subunit paralogue Btt1 led to only a partial or slight reduction in mitophagy. We also found that phosphorylation of Atg32, a crucial step for priming mitophagy, is decreased in the absence of Egd1. Forced Atg32 hyperphosphorylation almost completely restored mitophagy in egd1-null cells. Together, we propose that Egd1 acts in Atg32 phosphorylation to facilitate mitophagy.

Varus placement of the tibial component reduces the potential risk of fracture with adequate bony coverage in the Oxford unicompartmental knee arthroplasty.

A short keel-cortex distance (KCD), especially to the posterior cortex, is a potential risk factor for tibial plateau fracture after Oxford mobile-bearing unicompartmental knee arthroplasty (OUKA). This study aimed to evaluate the effect of tibial component alignment in the coronal plane and tibial proximal morphology on the KCD. Included in this study were 51 patients scheduled for primary Oxford medial unicompartmental knee arthroplasty (UKA). The anterior and posterior KCD were preoperatively assessed using 3D simulation software with the component set perpendicular to the tibial mechanical axis (neutral), 3° valgus, 3° varus, and 6° varus, relative to neutral alignment. We evaluated the existence of overhanging medial tibial condyle where the medial eminence line, the line including the medial tibial eminence parallel to the tibial axis, passes outside of the tibial shaft. In all component alignments, patients with a medial overhanging condyle had significantly shorter posterior KCD than those without. In patients with a medial overhanging condyle, the posterior KCD significantly increased when the tibial component was placed in 3° varus (4.6 ± 1.5 mm, P = 0.003 vs neutral, P < 0.001 vs 3° valgus) and 6° varus (5.0 ± 1.4 mm, P < 0.001 vs neutral, P < 0.001 vs 3° valgus) compared with in neutral (3.5 ± 1.9 mm) or 3° valgus (2.8 ± 1.8 mm). In OUKA, varus implantation increased the KCD. This could potentially decrease the risk of fracture, even in knees with the overhanging medial condyle. Conversely, valgus implantation of the tibial component shortened the KCD, and should therefore be avoided.

Public Health Centers' Training Session Programs to Develop Programs on Infection Control Practices for Multidrug-Resistant Organisms in Hospitals in Kawaguchi City, Japan.

Introduction The Kawaguchi City Public Health Center (PHC) conducted training sessions focusing on infection control practices on multidrug-resistant organisms (MDROs) for 19 hospitals and eight affiliated clinics (AFs) with beds in June 2022. Issues with infection control programs were identified via a survey implemented following the training sessions. These included providing feedback on infection control policies for MDROs, hand hygiene compliance programs (HHCPs), environmental cleaning (EC), and training sessions programs that hospitals or AFs with beds (hospitals) intended to implement in the future or develop (to be developed). We planned to examine whether the PHC training sessions programs have an effect on the development of hospital infection control programs designed to address these issues. The purpose of this study is to clarify the training session program provided by the Kawaguchi City PHC, which was effective in developing hospital infection control programs based on the results of the survey conducted after the training session. Methods In June 2023, a second training session that offered information on infection control practices was completed for 30 hospitals. This was followed by sending a questionnaire. We examined infection control programs to be developed and analyzed associations with the first learned information by training session (the first learned information). Results Twenty-four hospitals responded to the survey with a response rate of 80.0%. Half the respondents (12, 50.0%) had prepared for the infection control policy on carbapenem-resistant Enterobacteriaceae (CRE), 11 hospitals (45.8%) had provided feedback on HHC, and four (16.7%) planned to conduct feedback on HHC. HHCPs were planned to be developed by 19 hospitals (79.2%), EC by five hospitals (20.8%), training session by 12 hospitals (50.0%), and screening of MDROs upon hospital admission (AS) by nine hospitals (37.5%). The first learned information, "the prevention of healthcare-associated infections and cost savings by implementing cleaning bundles (the effects of cleaning bundles)," was identified by 10 hospitals (41.7%), and "specific programs on providing feedback effective for developing hand hygiene compliance (specific feedback)" was learned by eight hospitals (33.3%). The first learned information regarding specific feedback was significantly associated with HHCPs to be developed (p = 0.044). The first learned information on the effects of cleaning bundles was significantly associated with HHCPs and HHC feedback to be developed (p = 0.023, 0.034). The training session programs were not significantly connected to EC, training session, or AS to be developed. Conclusions Infection control programs to be developed were linked to the provision of information on numerical effects by implementing specific feedback and cleaning bundles. We suggest that the PHC should develop infection control programs for the hospitals and provide training sessions, including numerical effects.

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

Elevated stress response marks deeply quiescent reserve cells of gastric chief cells.

Gastrointestinal tract organs harbor reserve cells, which are endowed with cellular plasticity and regenerate functional units in response to tissue damage. However, whether the reserve cells in gastrointestinal tract exist as long-term quiescent cells remain incompletely understood. In the present study, we systematically examine H2b-GFP label-retaining cells and identify a long-term slow-cycling population in the gastric corpus but not in other gastrointestinal organs. The label-retaining cells, which reside near the basal layers of the corpus, comprise a subpopulation of chief cells. The identified quiescent cells exhibit induction of Atf4 and its target genes including Atf3, a marker of paligenosis, and activation of the unfolded protein response, but do not show elevated expression of Troy, Lgr5, or Mist. External damage to the gastric mucosa induced by indomethacin treatment triggers proliferation of the quiescent Atf4+ population, indicating that the gastric corpus harbors a specific cell population that is primed to facilitate stomach regeneration.

Sleeping Beauty transposon mutagenesis identified genes and pathways involved in inflammation-associated colon tumor development.

Chronic inflammation promotes development and progression of colorectal cancer (CRC). To comprehensively understand the molecular mechanisms underlying the development and progression of inflamed CRC, we perform in vivo screening and identify 142 genes that are frequently mutated in inflammation-associated colon tumors. These genes include senescence and TGFß-activin signaling genes. We find that TNFα can induce stemness and activate senescence signaling by enhancing cell plasticity in colonic epithelial cells, which could act as a selective pressure to mutate senescence-related genes in inflammation-associated colonic tumors. Furthermore, we show the efficacy of the Cdk4/6 inhibitor in vivo for inflammation-associated colonic tumors. Finally, we functionally validate that Arhgap5 and Mecom are tumor suppressor genes, providing possible therapeutic targets for CRC. Thus, we demonstrate the importance of the inactivation of senescence pathways in CRC development and progression in an inflammatory microenvironment, which can help progress toward precision medicine.

Restricted Kinematically Aligned Total Knee Arthroplasty Following Failed Oxford Unicompartmental Knee Arthroplasty.

In this report, we describe how to revise a failed Oxford unicompartmental knee arthroplasty to kinematically aligned total knee arthroplasty (TKA). Its benefits are the maintenance of the native joint line along with the avoidance of supplemental parts, such as metal augments and stems. This can be applied to patients whose medial tibial cortex is well preserved. The distal cutting plane and rotation alignment are decided before the removal of the femoral component. The tibial cutting plane is up to 12 mm below the lateral joint surface and the varus is up to 5° below the extramedullary rod. Eventually, the native joint line and alignment along with the soft tissue envelope can be well maintained, similar to the restricted kinematically aligned TKA.

A ubiquitin-proteasome pathway degrades the inner nuclear membrane protein Bqt4 to maintain nuclear membrane homeostasis.

Aberrant accumulation of inner nuclear membrane (INM) proteins is associated with deformed nuclear morphology and mammalian diseases. However, the mechanisms underlying the maintenance of INM homeostasis remain poorly understood. In this study, we explored the degradation mechanisms of the INM protein Bqt4 in the fission yeast Schizosaccharomyces pombe. We have previously shown that Bqt4 interacts with the transmembrane protein Bqt3 at the INM and is degraded in the absence of Bqt3. Here, we reveal that excess Bqt4, unassociated with Bqt3, is targeted for degradation by the ubiquitin-proteasome system localized in the nucleus and Bqt3 antagonizes this process. The degradation process involves the Doa10 E3 ligase complex at the INM. Bqt4 is a tail-anchored protein and the Cdc48 complex is required for its degradation. The C-terminal transmembrane domain of Bqt4 was necessary and sufficient for proteasome-dependent protein degradation. Accumulation of Bqt4 at the INM impaired cell viability with nuclear envelope deformation, suggesting that quantity control of Bqt4 plays an important role in nuclear membrane homeostasis.

Incomplete Screw Thread Engagement of Proximal Fragment: A Possible Failure Risk After Internal Fixation for Femoral Neck Fractures.

Background For successful internal fixation for femoral neck fracture, the sliding mechanism of the screw is important because it can induce inter-fragmental compression. The thread should penetrate the fracture line and be located within the proximal fragment. If screw thread engagement is incomplete and a part of the thread remains within the distal fragment, the screw sliding can be disturbed, potentially leading to fixation failure. We hypothesized that screw thread in the fracture is a risk of fixation failure. Methods We studied 133 hips that underwent internal fixation for femoral neck fracture using dual sliding and compression screws (DSCS) with 20 mm threads. The existence of incomplete thread engagement and fixation failure (cut out, perforation, pseudoarthrosis, or femoral neck shortening) were evaluated on anteroposterior hip radiography postoperatively. The distances from the thread end to the fracture line, screw head to the femoral head cortex, and femoral head diameter were measured to analyze their relationships with any incomplete thread engagement and fixation failure. Differences in evaluation data were assessed using Fisher's exact test, Student's t-test, and receiver operating characteristic (ROC) analysis. Results Forty-six cases had at least one screw with incomplete thread engagement, and the other 87 hips had a complete engagement. The failure rate in the group of hips with incomplete thread engagement was significantly higher (7/46, 15.2%) than that in the group of hips with complete thread engagement (3/87, 3.4%) (P = 0.032). Incomplete thread engagement was found in 59 out of 266 screws (22.2%), and a femoral head ≤ 43.9 mm in diameter was associated with an increased risk of incomplete thread engagement. Most incomplete thread engagement screws (81.4%) had < 5 mm thread length within the distal fragment. Conclusion A partially threaded screw is a significant risk of fixation failure after internal fixation for a femoral neck fracture. The smaller femoral head diameter increases the possibility of incomplete thread engagement. Shortening the thread length by 5 mm may help to avoid incomplete thread engagement.

Kinematically Aligned Oxford Unicompartmental Knee Arthroplasty Using the Microplasty Instrumentation System.

This technical note demonstrates kinematically aligned Oxford unicompartmental knee arthroplasty using the Microplasty instrumentation system with custom-made devices. The medial joint line is evaluated preoperatively; if it is aligned and parallel with the lateral joint line, they are considered to comprise the coronal knee joint line (CJL). In this case, the coronal inclination of a spoon gauge inserted into the medial joint space indicates the CJL. Otherwise, an accessory spoon is inserted and connected to the medial spoon to refer to the posterior condylar line, which is considered the CJL. The tibial cutting block is then connected without changing the inclination of the spoon and the coronal tilt of the tibial extramedullary rod is adjusted, which is implemented with a custom-made ankle yoke. The remainder of the steps is then identical to the conventional Microplasty procedure. This technique can imitate the cutting line to the CJL, which might be considered ideal from mechanical and kinematic perspectives.

[Report on COVID-19 infection prevention and control training sessions for care homes provided by Kawaguchi city and comparison with those provided by the local governments in Japan].

Objectives　We compared COVID-19 prevention and control information provided to care homes (CHs) by the Kawaguchi City public health center (PHC), which utilizes our precedent advice on nfection, with the information from several local governments (LGs) in Japan. This study aimed to highlight the role of LG-associated doctors in providing information to CHs, utilizing their precedent advice on infection control in CHs and medical facilities. This study analyzed the sector and type of information the LGs should provide to CHs to prevent and control COVID-19.Methods　We compared training sessions on COVID-19 prevention and control information provided to CHs by the Kawaguchi City PHC with training sessions offered by several other LGs in Japan that are available on their websites.Results　The Kawaguchi City PHC has been providing COVID-19 information to CHs when needed, including prevention and control information, through their doctors, utilizing our precedent advice on infection control, management of health conditions of staff and residents, and early detection of COVID-19. In contrast, 68 LGs announced that they have provided training sessions to CHs for the prevention and control of COVID-19 through their official homepages from March to September 2022. These training sessions involved information dissemination by infection control specialist nurses (42.6%), clinic or hospital doctors (32.4%), infection control specialist doctors (11.8%), and staff from LG headquarters, PHC, or LG-associated doctors (51.5%). Among the 68 LGs, 41 provided information that included hand hygiene (95.1%), personal protective equipment (92.7%), proper ventilation (51.2%), and management of staff (90.2%) and resident (58.5%) health conditions. Furthermore, Kawaguchi City PHC and several LGs provided information for the early detection of COVID-19.Conclusion　We suggest that LGs provide COVID-19 training sessions conducted by LG doctors that include management of staff and resident health conditions, provision of early detection information, and utilization of precedent advice on infection in CHs and medical facilities.

PROX1 induction by autolysosomal activity stabilizes persister-like state of colon cancer via feedback repression of the NOX1-mTORC1 pathway.

Cancer chemoresistance is often attributed to slow-cycling persister populations with cancer stem cell (CSC)-like features. However, how persister populations emerge and prevail in cancer remains obscure. We previously demonstrated that while the NOX1-mTORC1 pathway is responsible for proliferation of a fast-cycling CSC population, PROX1 expression is required for chemoresistant persisters in colon cancer. Here, we show that enhanced autolysosomal activity mediated by mTORC1 inhibition induces PROX1 expression and that PROX1 induction in turn inhibits NOX1-mTORC1 activation. CDX2, identified as a transcriptional activator of NOX1, mediates PROX1-dependent NOX1 inhibition. PROX1-positive and CDX2-positive cells are present in distinct populations, and mTOR inhibition triggers conversion of the CDX2-positive population to the PROX1-positive population. Inhibition of autophagy synergizes with mTOR inhibition to block cancer proliferation. Thus, mTORC1 inhibition-mediated induction of PROX1 stabilizes a persister-like state with high autolysosomal activity via a feedback regulation that involves a key cascade of proliferating CSCs.

Is simultaneous bilateral unicompartmental knee arthroplasty and total knee arthroplasty better than simultaneous bilateral total knee arthroplasty?

INTRODUCTION: This retrospective study aims to clarify if there are benefits of performing unicompartmental knee arthroplasty (UKA) on just one indicated side in patients who undergo simultaneous bilateral knee arthroplasty. MATERIALS AND METHODS: We compared 33 cases of simultaneous bilateral UKA/total knee arthroplasty (TKA) (S-UT) with 99 cases of simultaneous bilateral TKA (S-TT). Comparison included blood tests [C-reactive protein (CRP), albumin, and D-dimer], the incidence of deep vein thrombosis (DVT), range of motion (ROM), and clinical scores before and 1 year after surgery. RESULTS: Clinical scores were not significantly different between the groups. The postoperative flexion angle was significantly better in UKA sides. Blood tests showed that the S-UT had a significantly higher albumin value at 4 and 7 days after surgery. The CRP value at 4 and 7 days, and the D-dimer value at 7 and 14 days after surgery were significantly lower in the S-UT. The S-UT had significantly lower incidence of DVT. CONCLUSIONS: In cases of bilateral arthroplasty, if there is an indication on only one side, a better flexion angle can be obtained by UKA on that side, and with less surgical invasion. Moreover, the incidence of DVT is low, which is considered to be a benefit of performing UKA on just one side.

HIV viral protein R induces loss of DCT1-type renal tubules.

Hyponatremia and salt wasting is a common occurance in patients with HIV/AIDS, however, the understanding of its contributing factors is limited. HIV viral protein R (Vpr) contributes to HIV-associated nephropathy. To investigate the effects of Vpr on the expression level of the Slc12a3 gene, encoding the Na-Cl cotransporter, which is responsible for sodium reabsorption in distal nephron segments, we performed single-nucleus RNA sequencing of kidney cortices from three wild-type (WT) and three Vpr-transgenic (Vpr Tg) mice. The results showed that the percentage of distal convoluted tubule (DCT) cells was significantly lower in Vpr Tg mice compared with WT mice (P < 0.05), and that in Vpr Tg mice, Slc12a3 expression was not different in DCT cell cluster. The Pvalb+ DCT1 subcluster had fewer cells in Vpr Tg mice compared with WT (P < 0.01). Immunohistochemistry demonstrated fewer Slc12a3+ Pvalb+ DCT1 segments in Vpr Tg mice. Differential gene expression analysis comparing Vpr Tg and WT in the DCT cluster showed Ier3, an inhibitor of apoptosis, to be the most downregulated gene. These observations demonstrate that the salt-wasting effect of Vpr in Vpr Tg mice is mediated by loss of Slc12a3+ Pvalb+ DCT1 segments via apoptosis dysregulation.