Early Postoperative Outcomes of Periprosthetic Femoral Fracture in Patients Over 90 Years of Age.

The number of total hip arthroplasty and bipolar hemiarthroplasty is increasing because of their good clinical outcomes and the aging population. Consequently, the incidence of periprosthetic femoral fractures (PFFs) is expected to increase in older patients with osteoporosis. Surgery is the first choice of treatment for PFF, except in Vancouver Type A fractures. However, surgical treatment of PFF, including open reduction and internal fixation (ORIF) and revision arthroplasty, is highly invasive, and high mortality rates have been reported. The indication for ORIF for PFF in very elderly patients at a high risk of complications remains controversial, and postoperative outcomes are uncertain. This study aimed to evaluate the postoperative outcomes of ORIF for PFF in elderly patients. We retrospectively analyzed four females with a mean age of 90.7 years (91-92 years) who underwent ORIF for PFF at our institution from September 2014 to January 2023. No cases of American Society of Anesthesiologists (ASA) grade 3 or higher were found. Three patients were classified as Vancouver Type B1, and one was classified as Vancouver Type C. Cementless stems were used in primary surgeries in all cases. To measure clinical outcomes, we investigated the patient's walking ability at 30 days, three months postoperatively, and the final follow-up. Mortality was assessed during the follow-up period. One patient could walk without walking aids preoperatively, two used a walking stick, and one used a walker. All patients remained hospitalized and underwent gait training with a walker at 30 days follow-up; however, at three months postoperatively and the final follow-up, no patient was unable to walk. No deaths occurred within one month of surgery. Three deaths occurred during follow-up: one within six months, one within one year, and one within five years of surgery. The postoperative ORIF results for PFF in patients aged > 90 years showed no fatal perioperative complications and low mortality within 30 days postoperatively. These results suggest that ORIF for PFF can be considered for elderly patients if the preoperative ASA grade is relatively low.

"Fix and flap" for an open fracture of the tibia in a 97-year-old patient: A case report of early internal fixation and free flap reconstruction.

INTRODUCTION: The incidence of open fractures in super-old patients has increased. "Fix and flap" procedures using early internal fixation and free flap reconstruction in super-old patients are rarely reported. PRESENTATION OF CASE: A 97-year-old woman presented to our emergency department after a car accident. She was diagnosed with an open fracture of the lower leg, and the open wound could not be closed after debridement. The tibia was fixed using an intramedullary nail on the day of injury, and the open wound was closed using a free latissimus dorsi myocutaneous flap on the sixth day. The flap was engrafted at the 1-year follow-up after the injury, and the patient was able to walk using a cane. DISCUSSION: To facilitate flap elevation and shorten the operative time, a flap with fewer vascular variants should be selected, and flow-through anastomosis that does not obstruct peripheral blood flow with a high patency rate is preferable. Reconstructive free flap surgery is preferably performed within 1 week of the initial injury to prevent fibrosis or scarring of recipient vessels. CONCLUSION: The "fix and flap" procedure, composed of early internal fixation and free flap reconstruction, is possible even in super-old patients through careful considerations of flap selection, methods of anastomosis of blood vessels, and timing of surgery. However, it is necessary to determine whether the affected limb can be preserved or amputated, and prolonged treatment must be avoided.

Association between bone marrow lesions and bone mineral density of the proximal tibia in end-stage osteoarthritic knees.

This retrospective cross-sectional study investigated the association between bone marrow lesions (BMLs) and bone mineral density (BMD) in the proximal tibia of end-stage osteoarthritic knees from a large patient sample. Overall, 1308 end-stage osteoarthritic knees were enrolled before total knee arthroplasty. The preoperative range of motion was recorded. Bone mineral density in the medial tibial plateau (MTP), lateral tibial plateau (LTP), and metaphysis were measured using dual-energy X-ray absorptiometry. The MTP/LTP, MTP/metaphysis, and LTP/metaphysis ratios were calculated. BMLs were scored using a whole-organ magnetic resonance imaging scoring system. The relationship between BMD and BML scores was investigated using linear regression analysis. The highest BMD was 0.787 ± 0.176 g/cm2 at the MTP, followed by 0.676 ± 0.180 g/cm2 and 0.572 ± 0.145 g/cm2 at the metaphysis and LTP, respectively. The prevalence of BMLs was 90.4% and 24.2% in the MTP and LTP, respectively. In women, higher BML scores at the MTP were positively correlated with the BMD of the MTP (p < 0.001, r = 0.278), MTP/LTP (p < 0.001, r = 0.267), and MTP/metaphysis ratios (p < 0.001, r = 0.243). Regression analysis showed that higher BML scores in the MTP were correlated with higher BMD in the MTP (p < 0.001) and lower BMD in the LTP (p < 0.001). High BML scores in the MTP were positively associated with high BMD in the MTP, which also induced the medial to lateral imbalance of BMD in the proximal tibia.

Central Sensitization and Postoperative Improvement of Quality of Life in Total Knee and Total Hip Arthroplasty: A Prospective Observational Study.

Background: While total knee arthroplasty (TKA) and total hip arthroplasty (THA) lead to excellent clinical outcomes, some patients experience residual surgical site pain and reduced satisfaction. This prospective observational study investigated the prevalence of preoperative and postoperative residual central sensitization (CS) after TKA and THA. The influence of residual CS on the improvement in quality of life (QOL) was also investigated. Methods: The participants were 40 patients who underwent TKA and 47 patients who underwent THA. CS was measured using the central sensitization inventory (CSI) questionnaire. Knee symptoms were evaluated using the Knee Injury and Osteoarthritis Outcome Scales (KOOS), and hip symptoms were evaluated using the Japanese Orthopedic Association Hip-disease Evaluation Questionnaires (JHEQ). General QOL was evaluated using EuroQOL (EQ-5D-5l). Regression analysis was performed to estimate factors related to low QOL after surgery. Results: Preoperatively, 47.5% of TKA patients and 66.0% of THA patients were CS positive (P=0.083), which reduced to 10.0% (P=0.042) and 25.5% (P=0.202), respectively, 3 months after surgery. Although the improvements in KOOS subscales and EQ-5D-5l scores in TKA patients with residual CS were significantly lower than in those without residual CS, residual CS status had no effect on JHEQ subscales and EQ-5D-5l scores in THA patients. Regression analysis indicated that EQ-5D-5l was negatively correlated with CSI in the TKA group (P=0.017). In contrast, CSI was not correlated with EQ-5D-5l in the THA group (P=0.206). Conclusion: Postoperative QOL improvement was achieved 3 months after THA regardless of residual CS status. In contrast, preoperative CS was negatively associated with the improvement in QOL after TKA.

A successful case of "temporary endoluminal bypass technique" using a guide extension catheter during thrombolysis for acute limb ischemia in the non-stenting zone.

It is still difficult to treat acute limb ischemia (ALI) in the non-stenting zone such as the popliteal artery. We describe a temporary endoluminal bypass technique for ALI in the non-stenting zone using a guide extension catheter. An 83-year-old female was admitted and diagnosed with ALI in her left leg. The angiogram showed a thrombotic obstruction of the left popliteal artery. Aspiration and dilation by angioplasty could not revascularize. Although Fogarty thrombectomy can be applicable, we avoided it because of its risk of complications and performed a temporary endoluminal bypass technique. After evaluating the occluded lesion by intravascular ultrasound, we delivered a guide extension catheter to fully cover it. Because it played the role of an endoluminal bypass, the blood flow to the distal tibial arteries could be confirmed in the angiogram. A thrombolytic drug was administered intra-arterially for the whole day, and the angiogram showed a reduction of the thrombus on postoperative day (POD) 1. On POD 2, the blood flow was maintained without flow limitation even after removing the catheter. Finally, she was discharged without any complications. This technique might be an alternative in cases of failed conventional treatments for ALI although further investigation needs to be undertaken. .

Successful wound healing of refractory digital ulcer in patient with systemic sclerosis by Waon therapy.

The treatment of digital ulcer (DU) in systemic sclerosis (SSc) has not been established. A 77-year-old female with a refractory DU in SSc on the right foot was transferred to our hospital. Wound healing had not been achieved despite several endovascular treatments (EVT) and minor amputations. We started Waon therapy 5 days per week as an adjunct therapy. She was placed in a far-infrared-ray dry sauna maintained at 45 °C for 15 min, and was subsequently kept to rest with soothing warmth using a blanket for additional 30 min outside the room. Gradually, the wound had become smaller and the skin perfusion pressure (SPP) had increased. The increase of the blood flow to the wound could be observed in the angiogram on day 109. An additional EVT on day 109 also accelerated wound healing. Finally, wound healing was completely achieved without additional amputations on day 173. In this presented case, Waon therapy contributed to increase of the blood flow to the wound, evidenced by SPP value. Waon therapy may serve as an effective adjunct therapy of DU in SSc. .

Ten-Year Long-term Results of Modified Cervical Double-door Laminoplasty With C3 Laminectomy Preserving the Semispinalis Cervicis Inserted Into the Axis Compared With Those of Conventional Cervical Laminoplasty.

STUDY DESIGN: A retrospective study. OBJECTIVE: To compare long-term clinical and radiologic outcomes between conventional double-door laminoplasty (LP) (group A) and cervical LP with C3 laminectomy (group B). SUMMARY OF BACKGROUND DATA: Cervical LP with C3 laminectomy preserving the semispinalis cervicis inserted into the axis decreased the patients' postoperative axial pain and muscle atrophy, prevented interlaminar bony fusion, decreased limitations of daily living activity, including reduced postoperative neck mobility, and maintained the cervical range of motion (ROM) more effectively than conventional cervical LP reattaching the semispinalis cervicis in the short-term. MATERIALS AND METHODS: Group A included 14 patients with an average age of 56.6 years at the time of surgery (follow-up rate 58.1%), and group B included 21 patients with an average age of 56.3 years at the time of surgery (follow-up rate 29.1%). We evaluated the clinical results, which included the Japanese Orthopaedic Association (JOA) score, JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiologic results, including C2-C7 ROM, number of interlaminar bony fusions and presence of new spondylolisthesis at C3. RESULTS: There were no significant differences in preoperative and postoperative JOA scores, recovery rate of JOA score, and JOACMEQ. Significantly fewer patients in group B experienced interlaminar bony fusion at C2-C3 compared with those in group A. There was no significant difference in the presence of new spondylolisthesis at C3. In patients with cervical spondylotic myelopathy, the rate of decrease of C2-C7 ROM was significantly less in group B than in group A. In patients with ossification of the posterior longitudinal ligament, there was no significant difference in the rate of decrease of C2-C7 ROM between the groups. CONCLUSIONS: C3 laminectomy prevented interlaminar bony fusion at C2-C3. C3 laminectomy maintained cervical ROM in patients with cervical spondylotic myelopathy. There were no adverse events due to C3 laminectomy at 10 years postsurgery.

Effect of teriparatide on ligamentum flavum mesenchymal stem cells isolated from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) within the spinal canal sometimes leads to severe myelopathy. Teriparatide (TPD) is a recombinant human parathyroid hormone (PTH) (1-34), which promotes osteogenesis of mesenchymal stem cells (MSCs) via PTH 1 receptor (PTH1R). Although ligamentum flavum (LF)-MSCs from patients with OPLL have a high osteogenic potency, the effect of TPD on them remains unknown. In this study, we determined PTH1R expression in LF-MSCs from patients with OPLL and investigated whether TPD promotes osteogenic differentiation in them. First, LF-MSCs were isolated from patients with OPLL and cervical spondylotic myelopathy (CSM) (controls). Cultured LF-MSCs were treated with different concentrations of TPD on days 0, 7, and 14. On day 21, osteogenic gene expression was quantified. Mineralization was measured based on optical density after Alizarin Red S staining. LF-MSCs from both groups expressed PTH1R at the same level. TPD did not enhance osteogenic gene expression and mineralization in LF-MSCs from both groups. TPD did not promote the osteogenic differentiation of LF-MSCs from patients with OPLL. Thus, it may be safe for patients with OPLL. However, further confirmation of our results with in vivo studies is necessary.

Accuracy of the Gutter Position in Cervical Double-door Laminoplasty Using Intraoperative Computed Tomography Navigation and the Factors Associated With C5 Palsy.

STUDY DESIGN: This was a prospective study. OBJECTIVE: This study aimed to investigate the accuracy of the gutter position after cervical double-door laminoplasty (LP) using intraoperative computed tomography (CT) navigation and the factors associated with C5 palsy. SUMMARY OF BACKGROUND DATA: There were some reports in which the gutter position and the width of decompression in cervical LP were associated with C5 palsy; however, there were few reports about the accuracy of the gutter position. MATERIALS AND METHODS: Thirty-three patients treated with cervical LP were enrolled. We marked our targeted gutter position on the lamina with a high-speed drill using intraoperative CT navigation and performed the LP procedure. The accuracy of the gutter position was evaluated with a postoperative CT scan. We measured the angle of the opened lamina (AOL), the proportion of the distance between the gutters and the distance of transverse diameter of spinal canal (PGSC) with a postoperative CT scan and spinal cord posterior shifting (SCPS) with preoperative and postoperative magnetic resonance imaging scans. We investigated the incidence of C5 palsy and analyzed AOL, PGSC, and SCPS between the C5 palsy (+) and (-) groups. RESULTS: The accuracy of all gutter positions was 78.4% (182/232). The accuracy of the gutter position at the right C4 and right C7 was lower than that at the other levels. The AOL in all cases was ~60 degrees. The PGSC was 90.1%-97.2%. The SCPS at C5 was the largest with 2.2 mm. C5 palsy occurred in 3 of 33 patients (9.1%). There were no significant differences in the AOL, PGSC, or SCPS between the 2 groups. CONCLUSIONS: The accuracy of the gutter position using intraoperative CT navigation was good. The incidence of C5 palsy was higher in this study than in the previous reports.

Anti-HB-EGF Antibody-Mediated Delivery of siRNA to Atherosclerotic Lesions in Mice.

For atherosclerotic cardiovascular diseases (ACD), gene therapy may be a potential therapeutic strategy; however, lack of effective and safe methods for gene delivery to atherosclerotic plaques have limited its potential therapeutic applications. To overcome this limitation, we developed a novel antibody-based gene delivery system (anti-HB-EGF/NA vector) by chemically crosslinking antibodies against human heparin-binding epidermal growth factor-like growth factor (HB-EGF). It has been shown to be excessively expressed in human atherosclerotic plaques and NeutrAvidin (NA) for conjugating biotinylated siRNA. Immunofluorescence staining and quantitative flow cytometry analysis using human HB-EGF-expressing cells showed both antibody-mediated selective cellular targeting and efficient intracellular delivery of conjugated biotin-fluorescence. Moreover, we demonstrated antibody-mediated significant and selective gene knockdown via conjugation with anti-HB-EGF/NA vector and biotinylated siRNA (anti-HB-EGF/NA/b-siRNA) in vitro. Furthermore, using high fat-fed human HB-EGF knock-in and apolipoprotein E-knockout (Hbegf hz/hz; Apoe-/-) mice, we demonstrated that the anti-HB-EGF/NA vector, conjugating biotin-fluorescence, increasingly accumulated within the atherosclerotic plaques of the ascending aorta in which human HB-EGF expression levels were highly elevated. Moreover, in response to a single intravenous injection of anti-HB-EGF/NA/b-siRNA in a dose-dependent manner, qPCR analysis of laser-dissected atherosclerotic plaques of the ascending aorta showed significant knockdown of the reporter gene expression. These results suggest that the anti-HB-EGF antibody-mediated siRNA delivery could be a promising delivery system for gene therapy of ACD.

Low-Dose Erythropoietin in Patients With ST-Segment Elevation Myocardial Infarction (EPO-AMI-II)　- A Randomized Controlled Clinical Trial.

BACKGROUND: Erythropoietin (EPO) has antiapoptotic and tissue-protective effects, but previous clinical studies using high-dose EPO have not shown cardioprotective effects, probably because of platelet activation and a lack of knowledge regarding the optimal dose. In contrast, a small pilot study using low-dose EPO has shown improvement in left ventricular function without adverse cardiovascular events.Methods and Results:We performed a multicenter (25 hospitals), prospective, randomized, double-blind, placebo-controlled, dose-finding study to clarify the efficacy and safety of low-dose EPO in patients with ST-segment elevation myocardial infarction (STEMI) under the Evaluation System of Investigational Medical Care of the Ministry of Health, Labor and Welfare of Japan. In total, 198 STEMI patients with low left ventricular ejection fraction (LVEF <50%) were randomly assigned to receive intravenous administration of EPO (6,000 or 12,000 IU) or placebo within 6 h of successful percutaneous coronary intervention. At 6 months, there was no significant dose-response relationship in LVEF improvement among the 3 groups tested (EPO 12,000 IU: 5.4±9.3%, EPO 6,000 IU: 7.3±7.7%, Placebo: 8.1±8.3%, P=0.862). Low-dose EPO also did not improve cardiac function, as evaluated by 99 mTc-MIBI SPECT or NT-proBNP at 6 months and did not increase adverse events. CONCLUSIONS: Administration of low-dose EPO did not improve LVEF at 6 months in STEMI patients (UMIN000005721).

Development of a novel one-step production system for injectable liposomes under GMP.

There are few methods available for injectable liposome production under good manufacturing practices (GMP). Injectable liposome production processes under GMP generally consist of liposome formation, size homogenization, organic solvent removal, liposome concentration control and sterilization. However, these complicated and separate processes make it difficult to maintain scalability, reproducibility and sterility. To overcome these limitations, we developed a novel one-step in-line closed liposome production system that integrated all production processes by combining the in-line thermal mixing device with modified counterflow dialysis. To validate the system, we produced liposomal cyclosporine A (Lipo-CsA) and lyophilized the liposomes. The three independent pilot batches were highly reproducible and passed the quality specifications for injectable drugs, demonstrating that this system could be used under GMP. The accelerated stability test suggested that the liposomes would be stable in long-term storage. This one-step system facilitates a fully automated and unattended production of injectable liposomes under GMP.

Ablation of IL-33 gene exacerbate myocardial remodeling in mice with heart failure induced by mechanical stress.

BACKGROUND AND PURPOSE: ST2 is one of the interleukin (IL)-1 receptor family members comprising of membrane-bound (ST2L) and soluble (sST2) isoforms. Clinical trials have revealed that serum sST2 levels predict outcome in patient with myocardial infarction or chronic heart failure (HF). Meanwhile, we and others have reported that ablation of ST2 caused exaggerated cardiac remodeling in both ischemic and non-ischemic HF. Here, we tested whether IL-33, the ligand for ST2, protects myocardium against HF induced by mechanical overload using ligand specific knockout (IL-33-/-) mice. METHODS AND RESULTS: Transverse aortic constriction (TAC)/sham surgery were carried out in both IL-33 and WT-littermates. Echocardiographic measurements were performed at frequent interval during the study period. Heart was harvested for RNA and histological measurements. Following mechanical overload by TAC, myocardial mRNA expressions of Th1 cytokines, such as TNF-α were enhanced in IL-33-/- mice than in WT mice. After 8-weeks, IL-33-/- mice exhibited exacerbated left ventricular hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis, inflammation, and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33-/- mice than those in WT mice. CONCLUSIONS: We report for the first time that ablation of IL-33 directly and significantly leads to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data highlight the cardioprotective role of IL-33/ST2 system in the stressed myocardium and reveal a potential therapeutic role for IL-33 in non-ischemic HF.

Targeted Therapy for Acute Autoimmune Myocarditis with Nano-Sized Liposomal FK506 in Rats.

Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.

Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction.

RATIONALE: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. OBJECTIVE: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. METHODS AND RESULTS: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane-resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase-12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. CONCLUSIONS: Doxorubicin activated the ER stress-initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose-regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment.

Impact of contrast-induced acute kidney injury on outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PURPOSE: The purpose of this study was to identify predictors of contrast-induced acute kidney injury (CI-AKI) and the effect of CI-AKI on cardiovascular outcomes after hospital discharge in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). METHODS AND MATERIALS: We retrospectively reviewed 194 STEMI consecutive patients who underwent primary PCI to evaluate the predictors for CI-AKI and 187 survivors to examine all-cause mortality and cardiovascular events. Outcomes were compared between patients with CI-AKI and those without CI-AKI, which was defined as an increase >50% or >0.5mg/dl in serum creatinine concentration within 48hours after primary PCI. RESULTS: CI-AKI occurred in 23 patients (11.9%). Multivariate analysis identified pre-procedural renal insufficiency as a predictor of CI-AKI, and this predictor was independent from hemodynamic instability and excessive contrast volume. Receiver-operator characteristics analysis demonstrated that patients with an estimated glomerular filtration rate (eGFR) of ≤43.6ml/min per 1.73m(2) had the potential for CI-AKI. Patients who developed CI-AKI had higher mortality and cardiovascular events than did those without CI-AKI (27.8% vs. 4.7%; log-rank P=.0003, 27.8% vs. 11.2%; log-rank P=.0181, respectively). Cox proportional hazards model analysis identified CI-AKI as the independent predictor of mortality and cardiovascular events [hazard ratio [HR]=5.36; P=.0076, HR=3.10; P=.0250, respectively]. CONCLUSIONS: The risk of CI-AKI is increased in patients with pre-procedural renal insufficiency, and eGFR is clinically useful in the emergent setting for CI-AKI risk stratification before primary PCI.

An estimation method for a cellular-state-specific gene regulatory network along tree-structured gene expression profiles.

BACKGROUND: Identifying the differences between gene regulatory networks under varying biological conditions or external stimuli is an important challenge in systems biology. Several methods have been developed to reverse-engineer a cellular system, called a gene regulatory network, from gene expression profiles in order to understand transcriptomic behavior under various conditions of interest. Conventional methods infer the gene regulatory network independently from each of the multiple gene expression profiles under varying conditions to find the important regulatory relations for understanding cellular behavior. However, the inferred networks with conventional methods include a large number of misleading relations, and the accuracy of the inference is low. This is because conventional methods do not consider other related conditions, and the results of conventional methods include considerable noise due to the limited number of observation points in each expression profile of interest. RESULTS: We propose a more accurate method for estimating key gene regulatory networks for understanding cellular behavior under various conditions. Our method utilizes multiple gene expression profiles that compose a tree structure under varying conditions. The root represents the original cellular state, and the leaves represent the changed cellular states under various conditions. By using this tree-structured gene expression profiles, our method more powerfully estimates the networks that are key to understanding the cellular behavior of interest under varying conditions. CONCLUSION: We confirmed that the proposed method in cell differentiation was more rigorous than the conventional method. The results show that our assumptions as to which relations are unimportant for understanding the differences of cellular states in cell differentiation are appropriate, and that our method can infer more accurately the core networks of the cell types.

A case of coronary artery fistula diagnosed in the right decubitus position by transthoracic echocardiography.

A 70-year-old woman was admitted to our hospital for a continuous heart murmur in the fourth intercostal space at the right sternal border. Routine echocardiography demonstrated aneurismal dilatation at the origin of right coronary artery. These findings suggested a coronary artery fistula, although its drainage site could not be identified. By shifting the patient to the right decubitus position, we could observe an abnormal color Doppler signal going from the right coronary artery into the right atrium, confirming coronary artery fistula. The right decubitus position may be helpful for the evaluation of abnormal anatomic and auscultatory findings.

Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging compared with right atrial appendage pacing.

BACKGROUND: Interatrial septum pacing (IAS-P) decreases atrial conduction delay compared with right atrial appendage pacing (RAA-P). We evaluate the atrial contraction with strain rate of tissue Doppler imaging (TDI) during sinus activation or with IAS-P or RAA-P. METHODS: Fifty-two patients with permanent pacemaker for sinus node disease were enrolled in the study. Twenty-three subjects were with IAS-P and 29 with RAA-P. The time from end-diastole to peak end-diastolic strain rate was measured and corrected with RR interval on electrocardiogram. It was defined as the time from end-diastole to peak end-diastolic strain rate (TSRc), and the balance between maximum and minimum TSRc at three sites (ΔTSRc) was compared during sinus activation and with pacing rhythm in each group. RESULTS: There were no significant differences observed in general characteristics and standard echocardiographic parameters except the duration of pacing P wave between the two groups. The duration was significantly shorter in the IAS-P group compared with the RAA-P group (95 ± 34 vs 138 ± 41; P = 0.001). TSRc was significantly different between sinus activation and pacing rhythm (36.3 ± 35.7 vs 61.6 ± 36.3; P = 0.003) in the RAA-P group, whereas no significant differences were observed in the IAS-P group (25.4 ± 12.1 vs 27.7 ± 14.7; NS). During the follow-up (mean 2.4 ± 0.7 years), the incidence of paroxysmal atrial fibrillation (AF) conversion to permanent AF was not significantly different between the two groups. CONCLUSIONS: IAS-P decreased the contraction delay on atrial TDI compared to RAA-P; however, it did not contribute to the reduction of AF incidence in the present study.