Delta-Grip Stitch for Medial Meniscus Posterior Root Repair.

Medial meniscus posterior root tear (MMPRT) is a common medial meniscus injury among elderly patients and often necessitates repair. Although the clinical outcomes of MMPRT repair have demonstrated improvements, subsequent second-look arthroscopy shows poor healing postrepair. Consequently, numerous repair techniques have been reported. Herein, we introduce a simple locking-suture method, the "delta-grip" stitch, for MMPRT repair. This technique exhibited sufficient pullout strength compared with conventional suturing methods, offering promising prospects for enhancing the outcomes of MMPRT repair.

Characterizing soluble immune checkpoint molecules and TGF-ß1,2,3 in pleural effusion of malignant pleural mesothelioma.

The clinical impact of soluble molecules in pleural effusion (PE) is unclear in patients with malignant pleural mesothelioma (MPM). In this single-center, retrospective, observational study, we assessed soluble forms of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and PD-1 ligand 1 (PD-L1) using enzyme-linked immunosorbent assays; three TGF-ß isoforms were measured via multiplex assay in PE of patients with fibrinous pleuritis (FP) or MPM, to assess relationships between the levels of six molecules, clinicopathological characteristics, and efficacy of immune checkpoint inhibitors. Soluble forms of CTLA-4, PD-L1, PD-1, TGF-ß1, TGF-ß2, and TGF-ß3 were variably produced in PE of FP (n = 34) and MPM (n = 79); we found significant relationships between the six molecules and clinicopathological features. Although none of the three soluble immune checkpoint molecules showed diagnostic or prognostic effects in patients with MPM, TGF-ß2 level in PE is a useful differential diagnostic marker between FP and MPM. Both TGF-ß1 and TGF-ß3 levels are promising prognostic markers for MPM. Moreover, we found that higher baseline levels of PD-1 soluble forms predicted the response to anti-PD1 monotherapy. Our findings identify novel diagnostic, prognostic, and predictive biomarkers for anti-PD1 therapy in patients with MPM.

Cachexia Index Is a Prognostic Indicator in Patients With Metastatic Urothelial Carcinoma Treated With Systemic Chemotherapy.

Background/Aim: Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy. Patients and Methods: The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan-Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS). Results: At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05]. Conclusion: CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.

An ingenious deep learning approach for pressure injury depth evaluation with limited data.

BACKGROUND: The development of models using deep learning (DL) to assess pressure injuries from wound images has recently gained attention. Creating enough supervised data is important for improving performance but is time-consuming. Therefore, the development of models that can achieve high performance with limited supervised data is desirable. MATERIALS AND METHODS: This retrospective observational study utilized DL and included patients who received medical examinations for sacral pressure injuries between February 2017 and December 2021. Images were labeled according to the DESIGN-R® classification. Three artificial intelligence (AI) models for assessing pressure injury depth were created with a convolutional neural network (Categorical, Binary, and Combined classification models) and performance was compared among the models. RESULTS: A set of 414 pressure injury images in five depth stages (d0 to D4) were analyzed. The Combined classification model showed superior performance (F1-score, 0.868). The Categorical classification model frequently misclassified d1 and d2 as d0 (d0 Precision, 0.503), but showed high performance for D3 and D4 (F1-score, 0.986 and 0.966, respectively). The Binary classification model showed high performance in differentiating between d0 and d1-D4 (F1-score, 0.895); however, performance decreased with increasing number of evaluation steps. CONCLUSION: The Combined classification model displayed superior performance without increasing the supervised data, which can be attributed to use of the high-performance Binary classification model for initial d0 evaluation and subsequent use of the Categorical classification model with fewer evaluation steps. Understanding the unique characteristics of classification methods and deploying them appropriately can enhance AI model performance.

Mobile bearing shows larger rollback motion than fixed bearing in total knee arthroplasty using a medial stabilising technique with a navigation system.

Purpose: This study aimed to investigate the intraoperative knee kinematics of cruciate-retaining total knee arthroplasty with a medial stabilising technique (MST-TKA) and compare the kinematics between mobile- and fixed-bearing MST-TKAs. We hypothesised that mobile-bearing MST-TKA would result in greater physiological kinematic motion than fixed-bearing MST-TKA. Methods: Twenty-one and 20 knees underwent mobile- and fixed-bearing MST-TKAs using a navigation system (Orthopilot® ver. 6.0; B. Braun Aesculap), respectively. In the preoperative and postoperative kinematic analysis, the knee was moved manually from 0° to 120°, and femoral anteroposterior translations of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were recorded every 0.1 s from 0° to 120°. Data were subsequently extracted from the software every 10° of flexion and compared between the two groups, and the correlation coefficients between preoperative and postoperative kinematics were calculated. Results: In the postoperative analysis, the MFC in the mobile-bearing group showed significant posterior translation at 100°, 110° and 120° compared to the fixed-bearing group (p < 0.01). Similarly, the LFC in the mobile-bearing group showed significant posterior translation at 100°, 110° and 120° compared to the fixed-bearing group (p < 0.05, p < 0.01 and p < 0.05, respectively). In the mobile-bearing group, the preoperative and postoperative anteroposterior translations of the MFC and LFC were correlated (p < 0.01), while in the fixed-bearing group, there was no correlation. Conclusion: The femoral rollback motion in the mobile-bearing MST-TKA correlated with the preoperative kinematics and was larger than that in the fixed-bearing group. Level of Evidence: Level II, therapeutic prospective cohort study.

Kinetics of pro- and anti-inflammatory spike-specific cellular immune responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: a prospective longitudinal study in Japan.

BACKGROUND: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. RESULTS: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. CONCLUSIONS: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Association Between MRI Signal Intensity of the Repaired Lateral Meniscus and Residual Anterolateral Knee Laxity After ACL Reconstruction.

Background: Anterolateral knee laxity (ALLx) has been linked to tears of the lateral meniscus (LM) and anterior cruciate ligament (ACL) injury. Purpose: To investigate the longitudinal relationship between the signal intensity (SI) of the repaired LM on magnetic resonance imaging (MRI) and residual ALLx after ACL reconstruction (ACLR). Study Design: Cohort study; Level of evidence, 3. Methods: Included were 87 patients who underwent double-bundle ACLR and lateral meniscal repair (mean age, 23.5 years; body mass index, 23.7 kg/m2; 56 women) at a single institution between 2010 and 2019. Proton density-weighted (PDW) and T2-weighted (T2W) MRI was performed at 3, 6, and 12 months postoperatively, and the SI ratio (SIR) was calculated as (SI of the repaired LM)/(SI of the posterior cruciate ligament). At the 12-month follow-up, ALLx was evaluated using the pivot-shift test; an International Knee Documentation Committee grade ≥1 indicated residual ALLx. Results: Overall, 12 patients (13.8%) exhibited ALLx at 12 months postoperatively. At 3 months postoperatively, the SIR on PDW images (SIR-PDW) was significantly higher in patients with ALLx versus those without ALLx (1.98 ± 0.77 vs 1.49 ± 0.52, respectively; P = .007); there was no difference in the SIR on T2W images between the groups. SIR-PDW at 3 months postoperatively was correlated negatively with patient age (r = -0.308, P = .004). When patients were stratified into a younger (≤22 years; n = 53; ALLx = 7 [13.2%]) and an older (>22 years; n = 34; ALLx = 5 [14.7%]) group, the area under the receiver operating characteristic curves (AUCs) for SIR-PDW in the younger group were statistically significant for predicting the prevalence of ALLx at all follow-up times (AUCs, 0.733-0.788) with optimal cutoff values of 2.00 at 3 months, 1.50 at 6 months, and 1.50 at 12 months. Logistic regression analysis revealed that if younger patients consistently had higher SIR-PDW values than the cutoff values, they were more likely to have residual ALLx (odds ratios, 10.24-23.57). Conclusion: For younger patients who underwent both ACLR and lateral meniscal repair, higher MRI SI of the repaired LM was associated with a higher prevalence of residual ALLx.

Albuterol Delivery via In-Line Intrapulmonary Percussive Ventilation Superimposed on Invasive Ventilation in an Adult Lung Model.

BACKGROUND: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosolized medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT), whereas drug delivery via IPV during invasive ventilation is not well characterized. We hypothesized that drug delivery via IPV-invasive ventilation would differ from IPV alone due to control of ventilation by invasive ventilation. METHODS: An adult ventilator circuit was used for IPV-invasive ventilation. A normal or a diseased lung model was configured to airway resistance of 5 cm H2O/L/s and lung compliance of 100 mL/cm H2O or to airway resistance of 20 cm H2O/L/s and lung compliance of 50 mL/cm H2O, respectively. The ventilator settings were the following: pressure control continuous mandatory ventilation mode, 10 breaths/min; PEEP, 5 cm H2O; FIO2 , 0.21; inspiratory time, 1 s; no bias flow; and inspiratory pressure, 10 or 15 cm H2O for the normal or the diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from an IPV device was captured in a filter placed before the lung model and quantitated by spectrophotometry. RESULTS: The maximum efficiency of albuterol delivery via IPV-invasive ventilation was not different from that via IPV alone (mean ± SD of loading dose, 3.7 ± 0.2% vs 4.2 ± 0.3%, respectively; P = .12). The mean ± SD albuterol delivery efficiency with IPV-invasive ventilation was lower for the diseased lung model versus the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%; P < .001), which increased with decreasing percussion frequency. In contrast, the mean ± SD VT was lower for the normal lung model versus the diseased model (401 ± 14 mL vs 470 ± 11 mL; P < .001). CONCLUSIONS: Albuterol delivery via IPV-invasive ventilation was modulated by percussion frequency but was not increased with increasing VT. The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

A new neural network model that detects graft ruptures and contralateral anterior cruciate ligament injuries.

PURPOSE: The purpose of this study was to develop a neural network model for predicting second anterior cruciate ligament (ACL) injury risk following ACL reconstruction using patient features from medical records. METHODS: Of 486 consecutive patients who underwent primary unilateral ACL reconstruction, 386 patients (198 women, 188 men) with a mean age of 25.1 ± 11.6 years were included in this study. Fifty-eight features, including demographic data, surgical, preoperative and postoperative data, were retrospectively collected from medical records, and features with an incidence of less than 5% were excluded. Finally, 14 features were used for the analysis. The multilayer perceptron was composed of four hidden layers with a rectified linear unit as activation and was trained to maximise the area under the receiver-operating characteristic curve (auROC). Subsequently, validation was carried out through a rigorous threefold cross-validation process. To ascertain the most efficacious combination of features with the highest auROC, a single feature with the least impact on auROC maximisation was systematically eliminated from the comprehensive variable set, ultimately resulting in the retention of a mere two variables. RESULTS: The median follow-up period was 50.5 (24-142) months. Fifty-seven knees had a second ACL injury, with a graft rupture rate of 7.7% and a contralateral injury rate of 6.9%. The maximum auROC for predicting graft rupture was 0.81 with two features: young age and hamstring graft. Meanwhile, the maximum auROC for predicting contralateral ACL injury was 0.74 with seven features, including young age, presence of medial meniscus tear, small body mass index, hamstring graft, female sex and medial meniscus repair or treatment. CONCLUSION: A neural network model with patient features from medical records detected graft ruptures and contralateral ACL injuries with acceptable accuracy. This model can serve as a new, useful tool in clinical practice to inform decisions about ACL reconstruction and retuning to sports postoperatively. LEVEL OF EVIDENCE: Level IV.

Anterior-Posterior Center of Pressure Is Associated With Knee Extensor Moment During Landing After Anterior Cruciate Ligament Reconstruction.

CONTEXT: A reduced knee extensor moment (KEM) in the involved limb and asymmetry in the KEM during landing tasks are observed after anterior cruciate ligament reconstruction (ACLR). There is limited information about the association of kinetic and kinematic parameters with the KEM during landing after ACLR. This study investigated the association of the anterior-posterior center of pressure (AP-COP) position, vertical ground reaction force (VGRF), and lower limb joint angles with the KEM during landing in female athletes following ACLR. DESIGN: Cross-sectional study. METHODS: Twenty-two female athletes who underwent ACLR performed a drop vertical jump at 7.9 (1.7) months after surgery. We evaluated the KEM, AP-COP position, VGRF, and sagittal plane hip, knee, and ankle angles using a 3-dimensional motion analysis system with force plates. RESULTS: The peak KEM in the involved limb was significantly smaller than that in the uninvolved limb during landing (1.43 [0.33] N·m/kg/m vs 1.84 [0.41] Nm/kg/m, P = .001). The VGRF in the involved limb was significantly smaller than that in the uninvolved limb (11.9 [2.3] N/kg vs 14.6 [3.5] N/kg, P = .005). The limb symmetry index of the KEM was predicted by that of the VGRF (P < .001, R2 = .621, ß = 0.800). The KEM was predicted by the AP-COP position in the involved limb (P = .015, R2 = .227, ß = 0.513) and by the VGRF in the uninvolved limb (P = .018, R2 = .213, ß = 0.500). No significant correlation was noted between the KEM and the lower limb joint angles. CONCLUSIONS: The AP-COP position and VGRF were associated with the KEM during landing. Evaluating the VGRF and AP-COP position, not the lower limb joint angles, may contribute to understanding the KEM during double-leg landing after ACLR in the clinical setting.

Cartilage regeneration is related to superior mid-term patient-reported outcomes after open-wedge high tibial osteotomy.

PURPOSE: Medial open-wedge high tibial osteotomy (OWHTO) is related to cartilage improvement in the medial compartment. This study aimed to evaluate factors associated with cartilage improvement and patient-reported outcomes (PRO) after OWHTO. It was hypothesised that cartilage improvement is associated with favourable PRO. METHODS: This retrospective study included 94 patients who underwent OWHTO. The mean follow-up period was 5 years. The weight-bearing line ratio (WBLR) was defined as the ratio of the distance from the medial tibial edge to the tibial insertion of the weight-bearing line and the tibial width. The International Cartilage Research Society grade evaluated the medial femoral condyle (MFC) and medial tibial plateau (MTP) at initial and second-look arthroscopy, and cartilage improvement after OWHTO was assessed. Postoperative knee injury and osteoarthritis outcome scores (KOOS) were compared between the groups with improved and non-improved cartilage. Additionally, factors related to cartilage improvement and postoperative KOOS scores were analysed. RESULTS: Regarding the MFC, KOOS pain, symptoms, activities of daily living (ADL) and quality of life (QOL) were significantly higher in the cartilage-improved group than in the non-improved group (p = 0.012, 0.003, 0.001, 0.006), and cartilage improvement was significantly related to KOOS pain, ADL and QOL (p = 0.021, 0.039, 0.013). In addition, the postoperative WBLR was associated with cartilage improvement, with a cutoff value of 54.0% (p = 0.046). Regarding the MTP, KOOS ADL and QOL (p = 0.026, 0.022) were significantly higher in the cartilage-improved group than in the nonimproved group. Body mass index (BMI) was significantly related to the postoperative QOL (p = 0.018) and associated with cartilage improvement, with a cutoff value of 25.9 kg/m2 (p = 0.002). CONCLUSION: A postoperative WBLR greater than 54.0% and a preoperative BMI below 25.9 kg/m2 were associated with cartilage improvement, positively impacting PRO after OWHTO. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

[Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer].

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

Hydrogen sulfide and polysulfides induce GABA/glutamate/D-serine release, facilitate hippocampal LTP, and regulate behavioral hyperactivity.

Hydrogen sulfide (H2S) and polysulfides (H2Sn, n ≥ 2) are signaling molecules produced by 3-mercaptopyruvate sulfurtransferase (3MST) that play various physiological roles, including the induction of hippocampal long-term potentiation (LTP), a synaptic model of memory formation, by enhancing N-methyl-D-aspartate (NMDA) receptor activity. However, the presynaptic action of H2S/H2Sn on neurotransmitter release, regulation of LTP induction, and animal behavior are poorly understood. Here, we showed that H2S/H2S2 applied to the rat hippocampus by in vivo microdialysis induces the release of GABA, glutamate, and D-serine, a co-agonist of NMDA receptors. Animals with genetically knocked-out 3MST and the target of H2S2, transient receptor potential ankyrin 1 (TRPA1) channels, revealed that H2S/H2S2, 3MST, and TRPA1 activation play a critical role in LTP induction, and the lack of 3MST causes behavioral hypersensitivity to NMDA receptor antagonism, as in schizophrenia. H2S/H2Sn, 3MST, and TRPA1 channels have therapeutic potential for psychiatric diseases and cognitive deficits.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Greater medial proximal tibial slope is associated with bone marrow lesions in middle-aged women with early knee osteoarthritis.

BACKGROUND: Bone marrow lesion (BML) is an important magnetic resonance finding (MRI) finding that predicts knee osteoarthritis. The purpose of this study was to investigate the influence of proximal tibial morphology on BML, including the spreading root sign (SRS), in women without radiographic knee osteoarthritis (OA). It was hypothesized that varus alignment and a greater posterior tibial slopes (PTS) are associated with BML. MATERIALS AND METHODS: A total of 359 female volunteers without knee OA who were participants in the Iwaki Health Promotion Project in 2017 or 2019 were enrolled. Participants were divided into the non-OA and early knee OA (EKOA) groups based on the Luyten's classification criteria. The presence of pathological cartilage lesions, BMLs, attritions, meniscal lesions and effusions was scored on T2-weighted fat-suppressed magnetic resonance imaging (MRI) according to the Whole-Organ MRI Scoring system. The medial proximal tibial angle (MPTA) and medial and lateral PTS (MPTS and LPTS, respectively) were measured. Regression and receiver operating characteristic (ROC) analyses were performed to reveal the relationship between BMLs and proximal tibial morphological parameters. RESULTS: Of the 359 participants, 54 (15%) were classified as having EKOA. The prevalence of cartilage lesions, BMLs, attritions, meniscal lesions and effusions was higher in the EKOA group than in the non-OA group. The two groups had no significant difference in the proximal tibial parameters. Regression analysis revealed that age and a smaller MPTA were associated with BML in both groups. Attrition (p = 0.029) and the MPTS (p = 0.025) were positively associated with BML in the EKOA group. CONCLUSION: The prevalence of BMLs was higher in women with EKOA and correlated with the varus and greater posterior slopes in those without radiographic knee OA. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Cross-Sectional Relationship Between Atrial Conduction Delay and Arterial Stiffness in Patients with Obstructive Sleep Apnea.

Aim: Prolonged P-wave duration (PWD), which indicates atrial conduction delay, is a potent precursor of atrial fibrillation (AF) that may be induced by obstructive sleep apnea (OSA). The cardio-ankle vascular index (CAVI), which is an arterial stiffness parameter, is elevated in patients with OSA; moreover, an increased CAVI is associated with atrial conduction delay through left atrium enlargement in association with left ventricular diastolic dysfunction. We aimed to examine the relationship between the CAVI and PWD in patients with OSA. Methods: We included patients with a sinus rhythm who underwent overnight polysomnography. We measured the PWD and CAVI on standard 12-lead electrocardiograms; further, we analyzed the relationship between PWD and CAVI. Results: We analyzed data from 300 participants (men, 89.0%; mean age, 52.3 ± 13.1 years; and body mass index, 26.2 ± 3.9 kg/m2). The mean PWD was 104.4 ± 10.4 ms while the mean CAVI was 7.5 ± 1.5. PWD was significantly correlated with CAVI (r = 0.478, p < 0.001); additionally, PWD and CAVI were directly associated with OSA severity (p = 0.002 and p = 0.002, respectively). Multivariate regression analysis revealed an independent significant correlation of PWD and CAVI with OSA severity. Conclusion: In patients with OSA, an increase in arterial stiffness is associated with atrial conduction delay.

SHI family transcription factors regulate an interspecific barrier.

Pre-zygotic interspecies incompatibility in angiosperms is an important mechanism to prevent unfavourable hybrids between species. Here we report our identification of STIGMATIC PRIVACY 2 (SPRI2), a transcription factor that has a zinc-finger domain and regulates interspecies barriers in Arabidopsis thaliana, via genome-wide association study. Knockout analysis of SPRI2/SRS7 and its paralogue SPRI2-like/SRS5 demonstrated their necessity in rejecting male pollen from other species within female pistils. Additionally, they govern mRNA transcription of xylan O-acetyltransferases (TBL45 and TBL40) related to cell wall modification, alongside SPRI1, a pivotal transmembrane protein for interspecific pollen rejection. SPRI2/SRS7 is localized as condensed structures in the nucleus formed via liquid-liquid phase separation (LLPS), and a prion-like sequence in its amino-terminal region was found to be responsible for the formation of the condensates. The LLPS-regulated SPRI2/SRS7 discovered in this study may contribute to the establishment of interspecific reproductive barriers through the transcriptional regulation of cell wall modification genes and SPRI1.

Factors Associated with Complications after Total Pharyngo-Laryngo-Esophagectomy and Free Jejunal Flap Reconstruction.

INTRODUCTION: Free jejunal flap (FJF) reconstruction is a standard procedure for pharyngeal and cervical esophageal defects resulting from head and neck cancer resection. However, improvements in patients' quality of life after surgery require a further statistical approach. METHODS: An observational, retrospective, multivariate analysis was designed to report the incidence of postoperative complications and their association with clinical factors in 101 patients who underwent total pharyngo-laryngo-esophagectomy and FJF reconstruction for head and neck cancer at a university hospital between January 2007 and December 2020. RESULTS: Postoperative complications were observed in 69% of patients. In the reconstructive site, anastomotic leak, observed in 8% of patients was associated with vascular anastomosis in the external jugular vein system (age-adjusted odds ratio [OR]: 9.05, p = 0.044) and anastomotic stricture, observed in 11% of patients was associated with postoperative radiotherapy (age-adjusted OR: 12.60, p = 0.02). Cervical skin flap necrosis was the most common complication (34%) and was associated with vascular anastomosis on the right cervical side (age- and sex-adjusted OR: 4.00, p = 0.005). CONCLUSION: Although FJF reconstruction is a useful procedure, 69% of patients suffer a postoperative complication. We suppose that anastomotic leak is related to the low blood flow resistance of the FJF and inadequate drainage of the external jugular venous system, and anastomotic stricture is related to the vulnerability of the intestinal tissue to radiation. Furthermore, we hypothesized that the location of the vascular anastomosis may affect the mesenteric location of the FJF and the dead space in the neck, leading to the development of cervical skin flap necrosis. These data contribute to increasing our knowledge about postoperative complications related to FJF reconstruction.

Impact of Lipoprotein (a) on Long-Term Outcomes in Patients With Acute Myocardial Infarction.

BACKGROUND: Lipoprotein (a) (Lp(a)) is a complex circulating lipoprotein, and there is increasing evidence it is a risk factor for atherosclerotic cardiovascular disease (ASCVD). This study aimed to investigate the influence of Lp(a) serum levels on long-term outcomes after acute myocardial infarction (AMI).Methods and Results: Between January 2015 and January 2018, we enrolled 262 patients with AMI who underwent coronary angiography within 24 h of the onset of chest pain and had available Lp(a) data enabling subdivision into 2 groups: high Lp(a) (≥32 mg/dL: n=76) and low Lp(a) (<32 mg/dL: n=186). The primary endpoint was major adverse cardiac events (MACE), which was defined as a composite of cardiac death, nonfatal MI, and readmission for heart failure. Multivariate Cox regression analysis was performed to identify the predictors of MACE. The incidence of MACE was significantly higher in the high Lp(a) group than in the low Lp(a) group (32.8% vs. 19.6%, P=0.004). Multivariate analysis showed that Lp(a) ≥32 mg/dL was an independent predictor of MACE (hazard ratio 2.84, 95% confidence interval 1.25-6.60, P=0.013). CONCLUSIONS: High Lp(a) levels were associated with worse long-term outcomes after AMI, so Lp(a) may be useful for risk assessment.