A 2-Year Prospective Study on the Differences in Prognostic Factors for Major Adverse Cardiovascular, Cerebrovascular and Renal Events Between Patients with Mild and Severe Chronic Kidney Disease.

Purpose/Method: No studies have reported on prognostic markers in patients with chronic kidney disease (CKD) according to the severity of the disease. Therefore, in this multicenter, prospective trial performed as part of the Gunma CKD SPECT Multicenter Study, we recruited 311 patients with CKD (eGFR < 60 min/mL/1.73 m2) including 50 patients on hemodialysis and followed them for 2 years. The study sample underwent stress 99mTc-tetrofosmin SPECT for suspected or possible ischemic heart disease. We evaluated the summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and cardiac function with electrocardiogram-gated SPECT. Then, we compared the differences in prognostic markers for major adverse cardiac, cerebrovascular, and renal events (MACCRE) between patients with mild CKD (30 min/mL/1.73 m2 ≤ eGFR <60 min/mL/1.73 m2; n=184) and those with severe CKD (eGFR <30 min/mL/1.73 m2; n=97). Results: Of 281 patients available for analysis, 91 experienced MACCRE. In a multivariate Cox proportional hazards analysis of factors related to MACCRE, in patients with mild CKD the significant prognostic markers were SDS (P=0.002) and end-systolic volume (ESV, P=0.034); and in the patients with severe CKD, they were eGFR (P=0.03) and diabetes-mellitus (DM, P=0.023). Conclusions: Our findings indicate that SDS and ESV are significant prognostic markers for MACCRE in patients with mild CKD and eGFR and DM are significant prognostic markers in patients with severe CKD.

Sequential chimeric free deep circumflex iliac artery bone flap and superficial circumflex iliac artery perforator flap from the same site for one-stage reconstructions of severe hand injury: A report of two cases.

Two flaps, namely the free vascularized iliac bone graft supplied by the deep circumflex iliac artery (DCIA) and the superficial circumflex iliac artery perforator flap supplied by the superficial circumflex iliac artery (SCIA), can be individually harvested from a single surgical field. We report two cases treated by these free flaps for severe hand injury with large skin defect and osteomyelitis. Sequential chimeric flaps were anastomosed between the ascending branch of the DCIA and the SCIA. The advantage of this method is more freedom in the flap insetting for complex tissue defects. For this reason, this method is also excellent for cosmetic appearance. Furthermore, donor site morbidity can be minimized because the flaps are harvested from the same site.

Most Important Prognostic Values to Predict Major Adverse Cardiovascular, Cerebrovascular, and Renal Events in Patients with Chronic Kidney Disease Including Hemodialysis for 2 Years.

Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular/cerebrovascular events. The aim of this study is to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) could predict cardiovascular/cerebrovascular events. In the Gunma-CKD SPECT Study, a multicenter prospective cohort trial, 311 patients with CKD (estimated glomerular filtration rate < 60 min/mL/1.73 m2) including 50 patients on hemodialysis underwent stress 99mTc-tetrofosmin SPECT for suspected ischemic heart disease and were followed for 2 years. The primary endpoint was the occurrence of cardiac death (CD), while the secondary endpoint was major adverse cardiovascular/cerebrovascular and renal events (MACCRE). MACCRE occurred in 91 out of 286 patients (CD in 13 and other MACCRE in 78 patients). According to a multivariate Cox analysis, hemoglobin (Hb) and end-systolic volume (ESV) were associated with CD (p < 0.05), while the summed difference score, diabetes mellitus (DM), and Hb were associated with MACCRE (p < 0.05). Kaplan-Meier analysis showed that the CD-free rate was higher in patients with ESV < 105 mL (log-rank, p = 0.0013), Hb > 12 g (log-rank, p = 0.0036), and a summed stress score < 6 (log-rank, p = 0.0058). The MACCRE-free rate was higher in patients with SDS = 0 (log-rank, p = 0.0097), without DM (log-rank, p = 0.0091), and with Hb > 12 g (log-rank, p = 0.0023). Myocardial perfusion SPECT parameters as well as renal anemia and DM can be reliable prognostic markers in patients with CKD including hemodialysis.

Natural Killer T Cell-Targeted Immunotherapy Mediating Long-term Memory Responses and Strong Antitumor Activity.

Current tumor therapies, including immunotherapies, focus on passive eradication or at least reduction of the tumor mass. However, cancer patients quite often suffer from tumor relapse or metastasis after such treatments. To overcome these problems, we have developed a natural killer T (NKT) cell-targeted immunotherapy focusing on active engagement of the patient's immune system, but not directly targeting the tumor cells themselves. NKT cells express an invariant antigen receptor α chain encoded by Trav11 (Vα14)-Traj18 (Jα18) gene segments in mice and TRAV10 (Vα24)-TRAJ18 (Jα18) in humans and recognize glycolipid ligand in conjunction with a monomorphic CD1d molecule. The NKT cells play a pivotal role in the orchestration of antitumor immune responses by mediating adjuvant effects that activate various antitumor effector cells of both innate and adaptive immune systems and also aid in establishing a long-term memory response. Here, we established NKT cell-targeted therapy using a newly discovered NKT cell glycolipid ligand, RK, which has a stronger capacity to stimulate both human and mouse NKT cells compared to previous NKT cell ligand. Moreover, RK mediates strong adjuvant effects in activating various effector cell types and establishes long-term memory responses, resulting in the continuous attack on the tumor that confers long-lasting and potent antitumor effects. Since the NKT cell ligand presented by the monomorphic CD1d can be used for all humans irrespective of HLA types, and also because NKT cell-targeted therapy does not directly target tumor cells, this therapy can potentially be applied to all cancer patients and any tumor types.

Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study.

PURPOSE: Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. METHODS: In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m(2)] undergoing stress (99m)Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. RESULTS: During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). CONCLUSION: Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD.

Surgical Treatment for Thoracic Myelopathy Due to Simultaneous Ossification of the Posterior Longitudinal Ligament and Ligamentum Flavum at the Same Level.

STUDY DESIGN: Retrospective review. OBJECTIVE: The aim of this study was to assess the clinical outcomes of surgery in patients with simultaneous ossification of the posterior longitudinal ligament (OPLL) and ossification of the ligamentum flavum (OLF) at the same thoracic spine level and identify the risk factors for poor outcomes. SUMMARY OF BACKGROUND DATA: OPLL complicated with OLF in the thoracic spine is a rare condition. The optimal treatment option for thoracic myelopathy due to OPLL and OLF remains controversial, and high risk of postoperative paralysis remains a major complication. METHODS: We conducted a retrospective review of clinical and radiographic records of 15 patients who underwent surgery for simultaneous OPLL and OLF at the same level. RESULTS: Simultaneous OPLL and OLF occurred in the upper thoracic spine in 3 patients (20%), mid-thoracic spine in 10 patients (67%), and lower thoracic spine in 2 patients (13%). Six, 4, 2, and 3 patients underwent posterior decompression, posterior decompression and fusion, posterior decompression and circumferential decompression through a posterior approach, and circumferential decompression and posterior fusion, respectively. The mean Japanese Orthopaedic Association score before surgery and at the final follow-up was 5.7±1.9 and 7.0±2.1 points, respectively, yielding a mean recovery rate of 16.5%. However, no significant difference was observed between preoperative and postoperative Japanese Orthopaedic Association scores. Two patients with mid-thoracic lesions reported postoperative lower extremity weakness. Mid-thoracic lesions and considerable blood loss were risk factors for poor surgical outcome. CONCLUSIONS: Simultaneous OPLL and OLF in the mid-thoracic spine was observed in two thirds of the patients. We suggest that simultaneous OPLL and OLF in this area has a relatively poor recovery and may be very challenging and risky to treat, regardless of the surgical method selected, and recommend early surgery for OPLL and OLF in the mid-thoracic spine.

Effects of statin therapy on cardiac sympathetic nerve activity and left ventricular remodeling in patients with chronic heart failure: a propensity score-matched analysis.

Statin therapy reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and prevents left ventricular (LV) remodeling in chronic heart failure (CHF) patients. We sought to evaluate the effects of statin therapy on CSNA, as evaluated by I-metaiodobenzylguanidine (MIBG) scintigraphy, and LV remodeling in CHF patients. This study was sub-analysis of our previous report of the result that the serial I-MIBG studies were the most useful prognostic indicator in CHF patients. Patients with CHF (n = 208; left ventricular ejection fraction <45%) but no cardiac events for at least 5 months before the study, were identified according to their history of decompensated acute heart failure requiring hospitalization. The patients underwent I-MIBG scintigraphy and echocardiography immediately before hospital discharge and after 6 months. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined by I-MIBG scintigraphy. The LV end-diastolic volume (EDV) and end-systolic volume (ESV) were also determined by echocardiography. We selected 164 patients and used propensity score matching to compare patients who received oral statin (n = 82), and those who did not (n = 82).The changes in I-MIBG scintigraphic parameters improved, and in echocardiographic LVEDV and LVESV reduced in the statin group compared with those in the non-statin group. Moreover, there were significant correlations between changes in the I-MIBG scintigraphic findings and those in the LVEDV (% denervation, r = 0.534, P < 0.001; H/M ratio, r =  -0.516, P < 0.001; and WR, r = 0.558, P < 0.001); or the LVESV (% denervation, r = 0.479, P < 0.001; H/M ratio, r =  -0.450, P < 0.001; and WR, r = 0.520, P < 0.001) in the statin group. In contrast, there was no relationship between these parameters in the non-statin group.Statin therapy not only improved CSNA, but also reduced LV volume, in other wards, prevented LV remodeling in CHF patients.