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.

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.

Albuterol delivery via in-line intrapulmonary percussive ventilation superimposed on conventional mechanical ventilation in an adult lung model.

Background: Intrapulmonary percussive ventilation (IPV) is frequently used for airway clearance, together with delivery of aerosols containing medications. Drug delivery via IPV alone increases with decreasing percussion frequency and correlates with tidal volume (VT) while drug delivery via IPV during conventional mechanical ventilation (IPV/CMV) is not well characterized. We hypothesized that drug delivery via IPV/CMV would take place differently from that via IPV alone due to control of ventilation by CMV. Methods: An adult ventilator circuit was used for IPV/CMV. A normal or diseased lung model was configured to airway resistance (Raw) 5 cm H2O/L/s and lung compliance (CL) 100 mL/cm H2O or Raw 20 cm H2O/L/s and CL 50 mL/cm H2O, respectively. The ventilator settings were: 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 diseased lung model, respectively, to reach VT 500 mL with IPV off. Albuterol nebulized from Phasitron 5 was captured in a filter placed before the lung model and quantitated by spectrophotometry. Results: The maximal efficiency of albuterol delivery via IPV/CMV was not different from that via IPV alone (3.7 ± 0.2% vs 4.2 ± 0.3%, mean ± SD of loading dose, P= .12). Albuterol delivery efficiency with IPV/CMV was lower for the diseased lung model than for the normal model (1.6 ± 0.3% vs 3.2 ± 0.5%, mean ± SD, P < .001), which increased with decreasing percussion frequency. In contrast, VT was lower for the normal lung model than for the diseased model (401 ± 14 mL vs 470 ± 11 mL, mean ± SD, P < .001). Conclusions: Albuterol delivery via IPV/CMV was modulated by percussion frequency but not increased with increasing VT The delivery efficiency was not sufficiently high for clinical use, in part due to nebulizer retention and extrapulmonary deposition.

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.

Spectroscopic Quantitative Measurement of the Cartilage Surface using Arthroscopy Correlates with a Conventional Macroscopic Grading System.

Purpose: To quantify the cartilage surface profile visualized during arthroscopic surgery and examine its clinical utility by comparing the results of quantitative measurements with a conventional grading system. Methods: Fifty consecutive patients diagnosed with knee osteoarthritis and who underwent arthroscopic surgery were included in this study. A 4 K camera system was used, and the cartilage surface profile was visualized using the augmented reality imaging program. The highlighted image was displayed in 2 colors: black (the worn cartilage area) and green (the part where the cartilage thickness was maintained). The percentage of the green area was calculated using ImageJ and used as an index of cartilage degeneration. The quantitative value was statistically compared with the International Cartilage Repair Society (ICRS) grade as a conventional macroscopic evaluation. Results: In the quantitative measurement, the median percentage of the green area was 60.7 at ICRS grades 0 and 1 (interquartile range [IQR], 67.3-51.0), 47.2 at grade 2 (IQR, 54.1-39.2), 36.5 at grade 3 (IQR, 43.2-30.4), and 34.0 at grade 4 (IQR, 38.5-29.3). There was a significant difference between the macroscopic grades, except for Grades 3 and 4. There was a significant negative correlation between macroscopic evaluation and quantitative measurement (r = -0.672, P < .001). Conclusions: The quantitative measurement of the cartilage surface profile using the spectroscopic absorption technique was significantly correlated with the conventional macroscopic grading system and demonstrated fair to good inter-rater and intra-rater reliabilities. Level of Evidence: Level II, diagnostic (prospective cohort study).

Ultra-high-field pharmacological functional MRI of dopamine D1 receptor-related interventions in anesthetized rats.

The dopamine D1 receptor (D1R) is associated with schizophrenia, Parkinson's disease, and attention deficit hyperactivity disorder. Although the receptor is considered a therapeutic target for these diseases, its neurophysiological function has not been fully elucidated. Pharmacological functional MRI (phfMRI) has been used to evaluate regional brain hemodynamic changes induced by neurovascular coupling resulting from pharmacological interventions, thus phfMRI studies can be used to help understand the neurophysiological function of specific receptors. Herein, the blood oxygenation level-dependent (BOLD) signal changes associated with D1R action in anesthetized rats was investigated by using a preclinical ultra-high-field 11.7-T MRI scanner. PhfMRI was performed before and after administration of the D1-like receptor agonist (SKF82958), antagonist (SCH39166), or physiological saline subcutaneously. Compared to saline, the D1-agonist induced a BOLD signal increase in the striatum, thalamus, prefrontal cortex, and cerebellum. At the same time, the D1-antagonist reduced the BOLD signal in the striatum, thalamus, and cerebellum by evaluating temporal profiles. PhfMRI detected D1R-related BOLD signal changes in the brain regions associated with high expression of D1R. We also measured the early expression of c-fos at the mRNA level to evaluate the effects of SKF82958 and isoflurane anesthesia on neuronal activity. Regardless of the presence of isoflurane anesthesia, c-fos expression level was increased in the region where positive BOLD responses were observed with administration of SKF82958. These findings demonstrated that phfMRI could be used to identify the effects of direct D1 blockade on physiological brain functions and also for neurophysiological assessment of dopamine receptor functions in living animals.

Comparison of Antera 3D® and TcPO2 for Evaluation of Blood Flow in Skin.

Background: There is a need for quick skin blood flow tests that can be performed in the wound healing field. Antera 3D® is a compact scanner using multispectral imaging. It can perform quick assessment of skin conditions. The purpose of the present study was to investigate the ability of the Antera 3D® to assess skin blood flow in comparison with transcutaneous partial pressure of oxygen (TcPO2) measurements. Methods: This study was conducted on 13 patients with a history of lower extremity ulcers. Measurements of hemoglobin average level (hereafter, Hb score) measured by Antera 3D® and TcPO2 measured by a transcutaneous blood gas monitor were obtained at the same sites on the dorsal foot and lower leg. Differences in Hb score and TcPO2 were analyzed by t-test for each measurement site and for the presence of peripheral arterial disease (PAD). The correlation between TcPO2 and Hb score was analyzed by Pearson's correlation coefficient. Results: Twenty-four limbs were tested. Hb score was higher (P < 0.001) and TcPO2 was lower (P = 0.056) in the dorsal foot compared to the lower leg. In the dorsal foot, Hb score was higher (P = 0.023) and TcPO2 was lower (P = 0.046) in patients with PAD compared to those without PAD. A significant negative correlation (r = -0.68; 95% confidence interval -0.85 to -0.38, P < 0.001) between TcPO2 and Hb score was observed in the dorsal foot. Conclusion: The negative correlation between TcPO2 and Hb score may reflect compensatory peripheral vasodilation due to occlusion or stenosis of central arteries. This study showed that Hb score measured by Antera 3D® may be related to skin blood flow.

Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis.

OBJECTIVES: The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period. METHODS: Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] - [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression. RESULTS: Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (ß: - 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025). CONCLUSIONS: Lower BMD could predict BML enlargement during a 2YFU period.

Effects of tumor-infiltrating CD8+ T cells, PD1/PD-L1 axis, and expression patterns of HLA class I on the prognosis of patients with malignant pleural mesothelioma who underwent extra-pleural pneumonectomy.

Programmed cell death protein-1 (PD1), PD1 ligand 1 (PD-L1), and human leukocyte antigen (HLA) class I molecule play pivotal roles in T cell-induced anti-tumor immunity; however, the clinical impact of these parameters in resected malignant pleural mesothelioma (MPM) cases is unknown. We immunohistochemically evaluated the tumor infiltrated lymphocytes (TILs), PD1/PD-L1 axis, and expression of HLA class I in resected specimens from 58 patients with MPM who underwent extra-pleural pneumonectomy (EPP). Higher infiltration of CD3-TIL, CD8-TIL, and PD1-TIL, loss of HLA class I, and overexpression of PD-L1 by tumor cells (PD-L1 TC) or immune cells (PD-L1 IC) were observed in 34 (58.6%), 27 (46.6%), 41 (70.7%), 45 (77.6%), 29 (50.0%), and 33 (56.4%) of 58 cases, respectively. Interestingly, the CD3-TIL score positively correlated with PD-L1 TC and PD1-TIL scores. HLA class I expression level was inversely correlated with the expression levels of PD-L1 TC and PD-L1 IC. Multivariate analysis showed that age, histology, and node metastasis were independent prognostic factors for 5-year overall survival (OS) and loss of HLA class I coincided with a positive prognosis (p = 0.011). The concomitant lack of infiltrating CD8+ T cells with no loss of HLA class I predicted worse 5-year OS (p = 0.007). Moreover, cluster classifications among multiple immunoparameters showed that categories among CD3/PD-L1 TC/HLA class I (p = 0.043), CD8/PD1/HLA class I (p = 0.032), CD8/PD-L1 TC/HLA class I (p = 0.011), and PD1/PD-L1 TC/HLA class I (p = 0.032) predicted 5-year OS in EPP cases for MPM. These immunoparameters could guide surgical indications for patients with MPM.

Concomitant Lateral Meniscus Tear is Associated with Residual Rotatory Knee Instability 1 Year after Anterior Cruciate Ligament Reconstruction: Case-cohort Study.

Lateral meniscus tear (LMT) accompanied by anterior cruciate ligament (ACL) injuries has been reported to provoke rotatory instability of the affected knee joint. Unfortunately, these previous papers did not determine whether LMT-derived rotatory knee instability is residual because only preoperative or time zero data exists. This study aimed to longitudinally investigate how the prevalence of comorbid LMT is associated with residual rotatory knee instability (RKI) 1 year after ACL reconstruction (ACLR). A total of 327 patients who underwent double-bundle ACLR (average age: 23.4 years, body mass index: 23.5 kg/m2, 215 females). The patients were divided into three groups based on arthroscopy: 1) intact lateral meniscus (LM); 2) unrepaired LMT; 3) repaired LMT. At the 1-year follow-up, the pivot-shift test was performed. The prevalence of RKI, determined according to IKDC grades (grade ≥1 denoted RKI), was compared with chi-square or Fisher's exact tests. Thirty-eight patients (11.6%) had RKI; 203 subjects (62.1%) showed LMT, and 124 patients were diagnosed with an intact LM. Out of the 203 patients, 79 (38.9%) underwent LM repair. RKI was more prevalent in the LMT group than in the intact group (13.8% versus 8.1%, p = 0.117; Odds ratio: 1.499 [95%CI: 0.864 - 2.600]). In addition, the prevalence of RKI was significantly higher in the LM-repair group than in the intact-LM group (17.7% versus 8.1%, p = 0.038; Odds Ratio: 2.455 [95%CI: 1.032 - 5.842]). Medial meniscus tear (MMT) was detected in 113 patients (34.6%); RKI prevalence was not statistically different between the intact-MM group and the MMT group (12.2% versus 10.6%, p = 0.681). The current cohort study clarified that LMT comorbid with ACL injury was longitudinally associated with increased RKI prevalence 1 year after ACLR. Therefore, patients who underwent both ACLR and LM repair demonstrated a significantly higher prevalence of residual RKI.