Kinesin Family Member B18 Is Related to Gastric Mucin Phenotype and Contributes to Gastric Cancer Progression by Regulating Epithelial-Mesenchymal Transition.

INTRODUCTION: Gastric cancer (GC) remains a common health concern worldwide and is the third leading cause of death in Japan. It can be broadly classified into gastric and intestinal mucin phenotypes using immunohistochemistry. We previously reported numerous associations of kinesin family member (KIF) genes and mucin phenotypes with GC. However, no previous studies have reported on the importance of KIF18B in GC using immunostaining. Thus, in this study, we investigated the expression and functions of KIF18B, which is highly expressed in gastric mucin phenotype GC. METHODS: We performed RNA-seq of gastric and intestinal mucin type GCs, and clinicopathological studies of the KIF18B we found were performed using 96 GC cases. We also performed functional analysis using GC-derived cell lines. RESULT: RNA-seq showed the upregulation of matrisome-associated genes in gastric mucin phenotype GC and a high expression of KIF18B. KIF18B was detected in 52 of the 96 GC cases (54%) through immunohistochemistry. Low KIF18B expression was significantly associated with poor overall survival (p < 0.01). Other molecules that were significantly associated with KIF18B were MUC5AC and claudin 18; these were also significantly associated with the gastric mucin phenotype. KIF18B small interfering RNA (siRNA)-transfected GC cells showed greater growth and spheroid colony formation than the negative control siRNA-transfected cells. Furthermore, expression of snail family transcriptional repressor 1 and cadherin 2 was significantly increased and that of cadherin 1 was significantly decreased in KIF18B siRNA-transfected GC cells. CONCLUSION: These findings not only suggest that KIF18B may be a useful prognostic marker, but also provide insight into the pathogenesis of the GC phenotype.

Factors associated with prolonged on-scene time in ambulance transportation among patients with minor diseases or injuries in Japan: a population-based observational study.

BACKGROUND: Prolonged prehospital time is a major global problem in the emergency medical system (EMS). Although factors related to prolonged on-scene times (OSTs) have been reported in patients with trauma and critical medical conditions, those in patients with minor diseases or injuries remain unclear. We examined factors associated with prolonged OSTs in patients with minor diseases or injuries. METHODS: This population-based observational study used the ambulance transportation and request call record databases of the Higashihiroshima Fire Department, Japan, between January 1, 2016, and December 31, 2022. The participants were patients with minor diseases or injuries during the study period. We performed a multivariable logistic regression analysis with robust error variance to examine the association between patient age, sex, severity, accident type, date and time of ambulance call, and the coronavirus disease 2019 (COVID-19) pandemic with prolonged OSTs. Prolonged OST was defined as ≥ 30 min from the ambulance arrival at the scene to departure. RESULTS: Of the 60,309 people transported by ambulance during the study period, 20,069 with minor diseases or injuries were included in the analysis. A total of 1,241 patients (6.2%) experienced prolonged OSTs. Fire accidents (adjusted odds ratio [aOR]: 7.77, 95% confidence interval [CI]: 3.82-15.79), natural disasters (aOR: 28.52, 95% CI: 2.09-389.76), motor vehicle accidents (aOR: 1.63, 95% CI: 1.30-2.06), assaults (aOR: 2.91, 95% CI: 1.86-4.53), self-injuries (aOR: 5.60, 95% CI: 3.37-9.32), number of hospital inquiries ≥ 4 (aOR: 77.34, 95% CI: 53.55-111.69), and the COVID-19 pandemic (aOR: 2.01, 95% CI: 1.62-2.50) were associated with prolonged OSTs. Moreover, older and female patients had prolonged OSTs (aOR: 1.18, 95% CI: 1.01-1.36 and aOR: 1.12, 95% CI: 1.08-1.18, respectively). CONCLUSIONS: Older age, female sex, fire accidents, natural disasters, motor vehicle accidents, assaults, self-injuries, number of hospital inquiries ≥ 4, and the COVID-19 pandemic influenced prolonged OSTs among patients with minor diseases or injuries. To improve community EMS, we should reconsider how to intervene with potentially modifiable factors, such as EMS personnel performance, the impact of the presence of allied services, hospital patient acceptance systems, and cooperation between general emergency and psychiatric hospitals.

Evaluating the efficacy of post-operative chemotherapy after curative resection of stage IV gastric cancer with synchronous oligo metastasis: a multicenter retrospective study.

BACKGROUND: Surgical resection of oligo-metastasis in gastric cancer (GC) is weakly recommended for patients without other incurable factors in the Japanese GC Treatment Guidelines. While post-operative chemotherapy is the standard treatment in patients with stage II or III GC, its efficacy for resected stage IV GC is unclear. This study aimed to evaluate the efficacy of post-operative chemotherapy after curative resection of GC with oligo-metastasis. METHODS: We retrospectively reviewed the medical records of patients with GC who were diagnosed with synchronous oligo-metastasis at 20 institutions in Japan between 2007 and 2012. The selection criteria were: adenocarcinoma, stage IV with oligo-metastasis at liver or lymph node without other distant metastasis, curative resection including synchronous oligo-metastasis, and no prior treatment of GC before surgery. RESULTS: A total of 110 patients were collected. Of the 94 eligible patients, 84 underwent gastrectomy with surgical resection of oligo-metastasis (39 [41%] liver metastasis and 55, [59%] distant lymph node metastasis), followed by post-operative chemotherapy with S-1 (S1: n = 55), S1 plus cisplatin (CS: n = 22), or Others (n = 7). Moreover, 10 patients did not receive post-operative chemotherapy (Non-Cx). The median overall survival (OS) was 35.2 and 11.1 months in the post-operative chemotherapy and Non-Cx groups (hazard ratio, 3.56; 95% confidence interval, 1.74-7.30; p < 0.001), respectively. In multivariable analysis, Non-Cx and age over 70 years were identified as poor prognostic factors for OS (p < 0.05). CONCLUSIONS: Curative resection followed by post-operative chemotherapy in patients with GC with synchronous oligo-metastasis showed favorable survival.

Long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis.

AIM: In this study, we aimed to investigate the long-term benefits of switching from oral to intravenous calcimimetics in patients on hemodialysis. MATERIALS AND METHODS: Patients on maintenance hemodialysis at our institution who switched from oral to intravenous calcimimetics between March 1, 2017 and October 31, 2018 were enrolled. We compared tablet number; chronic kidney disease-mineral and bone disorder (CKD-MBD)-related drug cost; and serum corrected calcium, serum phosphorous, and serum intact parathyroid hormone levels before and 1, 2, and 3 years after switching from oral to intravenous calcimimetics. RESULTS: There were 15 patients (11 males and 4 females; mean age 60.9 ± 9.2 years). The tablet numbers and CKD-MBD-related drug cost before and 3 years after switching to calcimimetics were 12.1 ± 8.1 tablets/day vs. 8.4 ± 5.0 tablets/day (p = 0.0371) and 9,654.5 ± 6,206.8 yen (87.8 ± 56.4 U.S. dollars)/week vs. 7,231.7 ± 3,490.9 yen (65.7 ± 31.7 U.S. dollars)/week (p = 0.0406), respectively. CONCLUSION: Switching from oral to intravenous calcimimetics decreased intact parathyroid hormone levels and reduced the tablet numbers and CKD-MBD-related drug cost for a long period without significant adverse effects.

Occurrence of fever in cell-free and concentrated ascites reinfusion therapy is not related to the primary disease or nature of ascites.

Cell-free and concentrated ascites reinfusion therapy (CART) is a treatment for refractory ascites wherein filtered and concentrated ascitic fluid is reinfused. Although fever is one of the side effects of CART, its cause is not clear. Patients who underwent at least one CART session between June 2011 and May 2021 at our medical center were retrospectively enrolled in the study. They were classified according to the primary disease and nature of ascites. Ninety patients were included in this study. Increase in body temperature (BT) after CART was observed, regardless of the primary disease and nature of ascites. The difference in temperature before and after CART did not differ based on the primary disease [cancerous (including hepatocellular carcinoma, ovarian cancer) and non-cancerous] and nature of ascites. Elevated BT and fever after CART are not related to the primary disease and nature of the ascites.

Subacute stent thrombosis with spontaneously resolved secondary thrombi in paroxysmal nocturnal hemoglobinuria: a case report.

BACKGROUND: Stent thrombosis (ST) is a serious complication; however, a method to prevent ST in patients with thrombophilic diseases has not been established. CASE PRESENTATION: We report a case of subacute ST in a patient with paroxysmal nocturnal hemoglobinuria (PNH) who was receiving continuous heparin treatment in addition to the usual dual antiplatelet therapy for contrast defects at the proximal site of the occluded right coronary artery and the proximal site of the left circumflex artery. Despite the resolution of thrombi in secondary lesions, subacute ST occurred. After percutaneous coronary intervention for ST, triple therapy, including oral anticoagulation for PNH-related thrombosis, was initiated. The patient subsequently underwent craniotomy hematoma removal for hemorrhagic cerebral infarction. CONCLUSIONS: Reported cases of ST in patients with PNH are very few, and this case adds evidence with respect to antithrombotic therapy in patients with thrombotic tendencies. Both thrombosis and bleeding should be considered when administering antithrombotic therapy to patients with thrombotic diseases. If there are specific treatments for thrombophilic diseases, they should be initiated early.

Combinational Elastography.

Heart failure (HF) can cause liver congestion and stiffness. Elastography is used to noninvasively measure organ stiffness. Liver fibrosis (LF) is monitored by shear wave and strain elastography. However, shear wave velocity (Vs) on shear wave elastography varies under the influence of fibrosis and congestion, and the LF index by strain elastography reflects only LF progression. Little is known about the usefulness of these methods in HF patients. This prospective study evaluated combined shear wave and strain elastography (i.e., combinational elastography) for assessing liver congestion. A total of 51 patients with HF (33 outpatients and 18 inpatients) and 10 healthy participants were included. Further, the relationships between combinational elastography and clinical characteristics in 51 patients with HF and the effects of medical treatment on these relationships in 18 inpatients with HF were investigated. Vs was significantly higher in the HF group than in the control group (1.68 ± 0.47 versus 1.21 ± 0.16, P = 0.002). The LF index did not significantly differ (1.39 ± 0.40 versus 1.33 ± 0.15, P = 0.680). Vs decreased after treatment (from 2.01 ± 0.61 to 1.62 ± 0.49 m/seconds; P = 0.026), while the LF index did not change (from 1.21 ± 0.29 to 1.26 ± 0.27; P = 0.664). Brain natriuretic peptide level (r = 0.343; P = 0.003) and composite congestion scores (r = 0.455; P < 0.001) were correlated with Vs. Combinational elastography is useful for assessing liver congestion, differentiating between liver congestion and fibrosis, and assessing therapeutic effects in HF patients.

Deep sedation predicts pressure injury in patients admitted to intensive care units.

BACKGROUND: Patients in intensive care units (ICU) are frequently prescribed sedatives, which might increase the risk for pressure injury (PI). Although the association between sedation and incidence of PI has been noted, the adequate sedation level to prevent the incidence of PI in patients admitted to ICU is still unclear. AIM: This study aimed to investigate the association between fluctuating sedation levels and the incidence of PI in patients admitted to ICU. STUDY DESIGN: We retrospectively reviewed the medical records of 104 patients admitted to ICU. Data regarding the length of ICU stay (LOS) and comorbid infection were abstracted from medical records. The Richmond Agitation-Sedation Scale (RASS) was scored twice per day, and the standardized RASS (S-RASS, summation of RASS values divided by the number of samples) was used to evaluate changes in sedation levels. RESULTS: Among the 104 included patients, 65 patients (62.5%) were male (median age: 68.0 years), and 13 patients (12.5%) had PI during ICU admission. S-RASS scores were lower in patients with PI than in those without PI (P = .0001) even after adjustment for confounders (OR [95%CI]: 0.14 [0.03-0.58], P = .006). The LOS and infections were higher in patients with PI than in those without PI (P < .0001 and P = .005, respectively). The cut-off value of S-RASS for PI incidence was -3.2 (sensitivity: 88%; specificity: 85%), and a significant predictor of PI incidence (HR [95%CI]: 20.07 [2.53-159.11], P = .005). CONCLUSIONS: Deeper sedation levels based on S-RASS scores, which account for the effects of fluctuating sedation levels, were a strong, highly accurate predictor of PI incidence in patients admitted to ICU. RELEVANCE TO CLINICAL PRACTICE: Assessing fluctuations in the level of sedation using the S-RASS might help to identify sedative-induced PI in patients admitted to ICU.

Occurrence of Torsade de Pointes prior to complete lead connection during pacemaker implantation.

Torsade de Pointes (TdP) can be triggered by a pacing spike on the T-wave, due to pacemaker undersensing. However, it is not widely known that this phenomenon can occur even during pacemaker implantation. An 84-year-old woman underwent pacemaker implantation for the treatment of a complete atrioventricular block with dyspnea. During the procedure, immediately following ventricular lead insertion and before torque wrench tightening, TdP was observed. Ventricular pacing was initiated by inserting the lead into the header of the generator; however, sensing remained unstable. T-waves associated with undersensed PVCs and ventricular pacing occurred simultaneously, resulting in a spike on the T-wave and TdP.

Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers.

BACKGROUND: Although unresectable or recurrent gastric cancers (GC) are frequently treated with platinum-based chemotherapy, response to treatment remains unpredictable. Because Schlafen 11 (SLFN11) is recently identified as a critical determinant of platinum sensitivity, we investigated the potential clinical utility of SLFN11 in the treatment of GC. METHODS: We analysed the correlation between SLFN11 expression and overall survival in 169 GC patients by our established immunohistochemical approach. The impact of SLFN11 expression on the response to platinum and transition of SLFN11 expression upon long-term treatment with platinum were examined using GC cell lines and organoids. RESULTS: GC patients with high-SLFN11 expression exhibited significantly better survival than those with low-SLFN11 expression, and the significance increased when we selected patients treated with platinum-based chemotherapy. Knockout of SLFN11 and reactivation of SLFN11 in GC cells conferred resistance and sensitivity to platinum, respectively. In GC cells and organoids, long-term treatment with oxaliplatin suppressed SLFN11 expression while imparting drug resistance. The acquired resistance to oxaliplatin was reversed by reactivation of SLFN11 with epigenetic modifying drugs. CONCLUSIONS: This is the first report revealing definitive clinical implications of SLFN11 in the treatment of GC patients and providing novel strategies for the drug selection based on SLFN11 expression.

Papillary muscle rupture after transcatheter aortic valve implantation.

Catheter-induced mitral regurgitation (MR) caused by mitral papillary muscle rupture can be a fatal complication of transcatheter aortic valve implantation (TAVI). We report a case involving an 89-year-old man who presented with symptomatic severe aortic stenosis. In addition, preoperative echocardiography showed accessory mitral valve tissue. Although moderate MR developed immediately after TAVI, severe MR caused by anterolateral papillary muscle rupture occurred 3 months after TAVI. As only a few case series have been published, our case report adds to the evidence base for this treatment strategy.

Clinical biomarkers in adjuvant chemotherapy for gastric cancer after D2 dissection by a pooled analysis of individual patient data from large randomized controlled trials.

BACKGROUND: Adjuvant therapy for gastric cancer is a standard among the world with no regimen selection criteria. Also, prognostic factors except for tumor staging have not been established. We aimed to identify prognostic and predictive markers for gastric cancer adjuvant therapy from large randomized controlled trials with standard lymph node dissection. METHODS: Three studies: ACTS-GC, CLASSIC, and SAMIT were found and selected for a pooled analysis, following PRISMA guideline. The integrity of individual participant data (IPD) was verified in the eligible 3527 patients registered, and fixed-effect model was used. The primary endpoint was relapse-free survival (RFS) and the secondary endpoint was overall survival (OS). RESULTS: Age was a significant prognostic factor in addition to tumor stages both in "surgery alone" and "adjuvant" groups. Adjuvant therapy was effective for every TN stage; however, it tended to be more effective in T1-2 than in T3-4. Also, it was more effective in low- or middle-BMI than in high-BMI group with Hazard ratio [HR]s: 0.58, 0.58, and 1.05, respectively. Capecitabine plus oxaliplatin (CAPOX) was more effective than S-1 for T1-2, N2-3, and differentiated type with HRs between 0.59 and 0.70, but with no difference among TNM stages. Combining histology to TN; the HRs in differentiated T1-2 N1-3 groups were between 0.29 and 0.45. For T3-4 N0-1 group, S-1 was likely to be effective, not significant. CONCLUSIONS: Age is a significant prognostic factor both in surgery alone and adjuvant group. CAPOX is more effective for differentiated T1-2 tumors with lymph node metastasis.

Trends Over Time in the Incidences of ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction During the Past Decade in a Rural Japanese High-Aged Population.

BACKGROUND: In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated.Methods and Results:This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use. CONCLUSIONS: This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.

Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance.

BACKGROUND: The attainment of drug resistance in gastric cancer (GC) is a problematic issue. Although many studies have shown that cancer stem cells (CSCs) play an important role in the acquisition of drug resistance, there is no clinically available biomarker for predicting oxaliplatin (L-OHP) resistance in relation to CSCs. Organoid technology, a novel 3D cell culture system, allows harboring of patient-derived cancer cells containing abundant CSCs using niche factors in a dish. METHODS: In this study, we established L-OHP-resistant gastric cancer organoids (GCOs) and evaluated their gene expression profile using microarray analysis. We validated the upregulated genes in the L-OHP-resistant GCOs compared to their parental GCOs to find a gene responsible for L-OHP resistance by qRT-PCR, immunohistochemistry, in vitro, and in vivo experiments. RESULTS: We found myoferlin (MYOF) to be a candidate gene through microarray analysis. The results from cell viability assays and qRT-PCR showed that high expression of MYOF correlated significantly with the IC50 of L-OHP in GCOs. Immunohistochemistry of MYOF in GC tissue samples revealed that high expression of MYOF was significantly associated with poor prognosis, T grade, N grade, and lymphatic invasion, and showed MYOF to be an independent prognostic indicator, especially in the GC patients treated with platinum-based chemotherapy. The knockdown of MYOF repressed L-OHP resistance, cell growth, stem cell features, migration, invasion, and in vivo tumor growth. CONCLUSIONS: Our results suggest that MYOF is highly involved in L-OHP resistance and tumor progression in GC. MYOF could be a promising biomarker and therapeutic target for L-OHP-resistant GC cases.

Association Between Atrial High-Rate Episodes and Ischemic/Major Bleeding Events in Patients With a Cardiac Implantable Electronic Device　- A 10-Year, Single-Center Historical Cohort Study.

BACKGROUND: An association between atrial high-rate episode (AHRE) and stroke has been reported, although data for the Asian population are limited. This study aimed to investigate the role of AHRE in ischemic and major bleeding events in patients who underwent a cardiac implantable electronic device (CIED) procedure.Methods and Results:This single-center historical cohort study included 710 patients (age: 78±11 years, 374 women) who underwent a CIED-related procedure between October 2009 and September 2019 at Shimane Prefectural Central Hospital (median follow-up period: 4.5 [2.5, 7] years, 3439 person-years). Based on the maximum AHRE burden, patients were divided into: (1) <6 min; (2) ≥6 min to 24-h; and (3) ≥24-h groups. The cumulative incidence of ischemic (ischemic stroke, systemic embolism, and transient ischemic attack) and major bleeding (≥3 Bleeding Academic Research Consortium bleeding criteria) events after the procedure were compared. Uni- and multivariate analyses were performed to identify factors associated with these events. The incidence of both events increased with the rising AHRE burden, being significantly higher in the ≥24-h group than in the <6 min group. Multivariate analysis found age ≥85 years to be the only independent factor associated with both events. CONCLUSIONS: Longer AHRE duration is associated with a high number of major bleeding and ischemic events. Monitoring these bleeding risks is mandatory when clinicians are considering anticoagulation therapy for such patients.

Clinical effectiveness and adverse events associated with tolvaptan in patients above 90 years of age with acute decompensated heart failure.

With the aging society, the number of very-elderly (VE) patients with acute decompensated heart failure (ADHF) is increasing. Although tolvaptan is recommended for patients with ADHF in whom conventional diuretic therapy is ineffective, few reports exist on VE patients over 90 years of age. Therefore, we aimed to evaluate the clinical effectiveness and adverse events associated with tolvaptan in VE patients with ADHF. From January 2011 to December 2018, we retrospectively studied 180 patients with ADHF who were first administered tolvaptan during hospitalization. Patients were divided into two groups, namely, VE patients who were ≥ 90 years of age (n = 32) and not-VE patients (NVE) who were < 90 years of age (n = 148). The primary effective endpoints were the total urine volume and change in body weight. The safety endpoints evaluated were the incidence of hypernatremia (≥ 150 mEq/L) and worsening renal function (WRF) at any time during hospitalization. The median [interquartile range] patient age was 93 [91-94] years in the VE group and 80 [69-85] years in the NVE group. The mean dose of tolvaptan for the first week of administration was similar between groups (7.9 ± 5.0 mg, VE group; 7.3 ± 3.7 mg, NVE group; p = 0.52). There were no significant differences between the two groups in the total urine volume at 24 h (1901 ± 666 mL, VE group; 2101 ± 1167 mL, NVE group; p = 0.33) and that at 48 h (3707 ± 1274 mL, VE group; 4195 ± 1990 mL, NVE group; p = 0.19) and in the mean change in body weight (- 2.5 ± 2.0 kg, VE group; -2.7 ± 2.4 kg, NVE group; p = 0.70). The median duration of hospitalization was 24 [20-9] and 31 [20-42] days in the VE and NVE groups, respectively (p = 0.67). The incidence of hypernatremia (6.3% (2/32), VE group; 3.4% (5/148), NVE group; p = 0.61) and WRF (25.0% (8/32) VE group; 19.6% (29/148), NVE group; p = 0.31) was similar between the groups. In conclusion, tolvaptan has similar clinical effectiveness in increasing urine volume and decreasing body weight, without increased adverse events, in VE patients with ADHF who were ≥ 90 years of age compared to NVE patients with ADHF.

[Investigation of the safety and usefulness of a renal biopsy for older elderly patients ≥75 years old].

AIM: We herein report the safety and usefulness of a kidney biopsy in older elderly patients (≥75 years old). METHODS: A retrospective observational study was conducted in older elderly patients who had received a renal biopsy at the Department of Nephrology, Shimane University Hospital, from January 1, 2008, to December 31, 2018. The native renal biopsy results of 52 later-stage elderly patients were analyzed (29 men and 23 women). RESULTS: The most common indication for a renal biopsy was nephrotic syndrome (n = 22), followed by rapidly progressive glomerulonephritis (n = 12) and asymptomatic urinary abnormalities (n = 12). The most common pathological diagnosis was membranous nephropathy (n = 12), followed by ANCA-associated nephritis (n= 8), minimal change nephrotic syndrome (6 case), membranoproliferative glomerulonephritis (n = 5), IgA nephropathy (n = 4), and diabetic nephropathy (n = 3). The concordance rate between the clinical and pathological diagnoses was 53.8%. The only complication of the renal biopsy was hemorrhaging requiring blood transfusion (1 patient; 1.9%). The hemoglobin level decreased by 0.5±0.05 d/dL after the biopsy. CONCLUSION: The rate of serious complications associated with a renal biopsy was comparable to that in previous reports in younger patient. Renal biopsies can therefore be safely performed even in older elderly patients. The concordance rate of the clinical and pathological diagnoses was about 50%. Therefore, renal biopsies should be performed in older elderly patients when necessary.

The Effectiveness of Target Low-Density Lipoprotein Cholesterol Achieved with Strict Management in Secondary Prevention of Long-Term Coronary Events in Japanese Patients.

BACKGROUND: In the secondary prevention of long-term coronary events, a target value of low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL is recommended as standard management in Japanese guidelines. However, the effectiveness of strict management on lowering LDL-C remains unclear. OBJECTIVES: To clarify whether strict management of LDL-C < 70 mg/dL is more effective in preventing long-term coronary event recurrence than standard management. METHODS: We retrospectively investigated 344 patients with previous percutaneous coronary interventions who underwent late coronary angiography to examine recurrence of cardiac ischemia beyond the early restenosis period from January 2007 to August 2019. Patients were stratified into three groups according to achieved LDL-C value; LDL-C < 70 mg/dL (n = 53), 70 to < 100 mg/dL (n = 130), and ≥ 100 mg/dL (n = 161). Endpoints were acute coronary syndrome (recurrent-ACS) and late coronary revascularization. RESULTS: After follow-up (median 6.0 years), 200 patients (58%) underwent late coronary revascularization, including 94 recurrent-ACS. The incidence of recurrent-ACS was significantly lower in the patients who achieved LDL-C < 70 mg/dL than in those with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.009 and p = 0.001, respectively). There was no significant difference between the patients with LDL-C 70 to < 100 mg/dL and LDL-C ≥ 100 mg/dL (p = 0.140). There was also no significant difference in late revascularization between the patients with LDL-C < 70 mg/dL and LDL-C 70 to < 100 mg/dL. In patients with LDL-C < 100 mg/dL (n = 183), LDL-C [hazard ratio (HR) 1.035, p = 0.007] and HbA1c (HR 1.338, p = 0.001) were independently associated with recurrent-ACS. CONCLUSIONS: In Japanese patients, LDL-C was a residual risk for recurrent-ACS even after recommended standard LDL-C lowering management target values had been achieved.

SPC18 Expression Is an Independent Prognostic Indicator of Patients with Esophageal Squamous Cell Carcinoma.

OBJECTIVES: Esophageal cancer is the sixth most common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and plays an important role in the secretion of proteins including transforming growth factor α (TGF-α). In this study, we investigated the significance of SPC18 expression in human esophageal squamous cell carcinoma (ESCC). METHODS: SPC18 expression was examined by immunohistochemistry. RNA interference was used to inhibit SPC18 expression in ESCC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The effects of SPC18 inhibition on epidermal growth factor receptor (EGFR) signaling were analyzed by Western blot. RESULTS: In total, 46 (50%) of 92 ESCC cases were positive for SPC18. SPC18 staining was observed more frequently in stage II/III/IV cases than in stage I cases (p = 0.028). We found that SPC18 expression was significantly associated with increased cancer-specific mortality (p = 0.006, log-rank test). SPC18 expression was frequently found in EGFR-positive cases compared with EGFR-negative cases. Cell proliferation and EGFR signaling were inhibited by SPC18 knockdown. CONCLUSION: Specific inhibitors of SPC18 may be promising anticancer drugs for patients with ESCC.

Using the preoperative prognostic nutritional index as a predictive factor for non-cancer-related death in post-curative resection gastric cancer patients: a retrospective cohort study.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Therefore, identifying the predictive factors for surgical morbidity, disease recurrence, and long-term survival is necessary for preventing GC patient mortality. We aimed to evaluate the factors that contribute to the poor prognoses of GC patients. METHODS: In this retrospective cohort study, the data of 182 patients who underwent curative gastrectomy for GC was reviewed. The data included patients' cancer stage and preoperative prognostic nutritional index (PNI) score. We identified the prognostic factors using a univariate analysis and the multivariable Cox proportional hazards model. The associations between PNI and other clinicopathologic factors for GC were compared via logistic regression analysis. Kaplan-Meier curves were used to evaluate patients' survival in relation to these factors. The median follow-up period was 3.5 years. Multivariable cumulative incidence method based on Fine and Gray's method was performed to evaluate the association between non GC-related death and potential prognostic factors. RESULTS: There were significant differences in overall survival (OS) between comorbidities (myocardial infarction: P = 0.040, liver disease: P = 0.017), cancer stages (I vs. II: P = 0.049, I vs. III: P < 0.001), tumor size (P = 0.002), lymphatic vessel infiltration (P < 0.001), serum CA 19-9 (P = 0.024), and PNI scores (P = 0.002). Moreover, only PNI score was determined to be an independent prognostic factor for survival. Furthermore, stage I GC patients with high PNI scores had significantly longer OS than those with low PNI scores (P < 0.001), but these groups were not significantly different in terms of recurrence-free survival (P = 0.756). Stage II and III GC patients showed no significant difference in terms of OS and recurrence-free survival, regardless of PNI scores. Finally, Fine and Gray's method revealed that PNI score was an independent prognostic factor for non-GC-related death (P < 0.001). CONCLUSIONS: Preoperative PNI is effective in predicting the prognosis of post-curative gastrectomy GC patients and can be used to predict non-GC-related death and the OS of post-curative gastrectomy patients with stage I GC.