Initial two-day blood pressure management after endovascular aneurysm repair improves midterm outcomes by reducing the incidence of early type II endoleak.

OBJECTIVE: The aim of this study was to evaluate midterm outcomes of our novel strategy of postoperative initial 2-day blood pressure management (BPM) after endovascular aneurysm repair (EVAR) for the prevention of subsequent type II endoleak (T2EL) in a single-center series. METHODS: Between 2008 and 2014, 137 patients who underwent EVAR for abdominal aortic aneurysm (AAA) were reviewed. Starting from 2013, the mean blood pressure was maintained between 75 and 90 mmHg for the initial 24 hours after EVAR followed by systolic pressure controlled below 120 mmHg during the next 24 hours in the treatment group (n = 76). The incidence of T2EL detected at 7 days, reintervention, and AAA sac diameter up to 5 years after EVAR were compared with those of the control group comprising of 60 consecutive patients who underwent standard EVAR without BPM prior to 2013. RESULTS: Between the treatment group and the control group, significant differences were achieved in the incidence of T2EL at 7 days (19.7% vs 40.0%; P = .009), a mean decrease of AAA sac diameter at 1-year (-5.1 ± 4.9 vs -2.2 ± 6.7 mm; P = .013) and 2-year (-5.4 ± 7.7 vs -1.7 ± 10.8 mm; P = .045). In addition, there was a significant decrease in the incidence of T2EL detected at 7 days with the use of the Gore Excluder with 22.7% in the treatment group vs 80.0% in the control group (P < .001), which resulted in a significant decrease in the aneurysm sac diameter up to 4 years after EVAR. Survival rate without AAA sac enlargement at 5 years after EVAR (83.0% vs 70.0%; P = .021) in the treatment group was significantly higher than that of the control group, whereas no significant differences were observed in the freedom rates of reintervention, T2EL-related reintervention, and all-cause mortality between the groups. CONCLUSIONS: Postoperative initial 2-day BPM had a preventive effect on AAA sac enlargement until midterm periods, by reducing the incidence of T2EL at 7 days after EVAR. The usage of Gore Excluder under BPM was especially associated with sustained positive effects until the midterm follow-up.

Injection of n-Butyl-2-Cyanoacrylate into the Abdominal Aortic Aneurysm Sac during Endovascular Aortic Repair to Prevent Type II Endoleaks Caused by Lumbar Arteries.

PURPOSE: To evaluate midterm results of whether the strategy to occlude target lumbar arteries using n-butyl-2-cyanoacrylate (nBCA) injection during endovascular aneurysm repair (EVAR) reduced the incidence of Type II endoleak (T2EL) after EVAR. MATERIALS AND METHODS: Between 2013 and 2020, 187 patients underwent EVAR; 106 in the treatment group received nBCA injection during EVAR, whereas 81 in the historical control group did not. The incidence of T2EL at 7 days, need for reintervention, and post-EVAR aneurysmal shrinkage were compared between the groups. RESULTS: Between the treatment group and the control group, significant differences were achieved in the incidence of T2EL (2.8% vs 28.4%; P < .0001) and decreased aneurysmal diameter was observed at 1 year after EVAR (-5.2 vs -3.8 mm; P = .034). In multivariate analysis, nBCA injection (odds ratio [OR], 0.04; P = .001) and younger age (OR, 0.92; P = .036) were significantly associated with a reduced incidence of T2EL. As a possible adverse event associated with nBCA injection, 2 cases of transient lower-limb motor dysfunction (1.9%) were observed. Propensity score analysis revealed that the treatment group had a significantly lower incidence of T2EL than that in the control group (P = .0002) even though there was no difference in the incidence of inferior mesenteric artery coil embolization between the groups. The survival rate without aneurysm sac enlargement (100.0% vs 69.8%; P = .014) and the reintervention-free rate (100.0% vs 63.1%; P = .034) in the treatment group were significantly higher than those in the control group. CONCLUSIONS: Concomitant nBCA injection can provide durable EVAR without T2EL, as supported by the avoidance of reintervention associated with aneurysm sac enlargement.

What Affects Healing Rates in Patients Treated for Medication-Related Osteonecrosis of the Jaw? The Role of Operative Therapy and Other Clinical Factors.

BACKGROUND: In the therapy of medication-related osteonecrosis of the jaw (MRONJ), the healing rate, effectiveness of operative therapy, and factors associated with healing remain unclear. PURPOSE: This study aimed to estimate MRONJ therapy healing rates and identify associated prognostic factors. STUDY DESIGN, SETTING, SAMPLE: A 25-center prospective cohort study was conducted on 291 patients with MRONJ treated with a common therapeutic protocol during 2013-2016. Patients unable to continue examinations or treatment were excluded. PREDICTOR VARIABLE: The primary predictor variable was MRONJ therapy grouped into two categories: operative and nonoperative. Secondarily, the prognostic factors categorized as demographic, medical, clinical, and perioperative were evaluated. MAIN OUTCOME VARIABLES: The primary outcome variable was treatment duration, defined as the time (in months) between the initiation of therapy and when the site was healed or the date of the final visit or loss to follow-up. COVARIATES: Not applicable. ANALYSES: Descriptive statistics and 3-year cumulative healing rates were calculated. The association between clinical factors and time to healing was analyzed using bivariate and multivariate analyses and propensity score analysis. P < .05 was considered significant. RESULTS: We analyzed data from 291 subjects with 76 (26.1%) and 215 (73.9%) subjects in the operative and nonoperative therapy groups, respectively. The healing rates for operative and nonoperative therapies were 95.8 and 70.7%, respectively (hazard ratio [HR] = 1.6, 95% confidence interval [CI] = 1.1-2.2, P value [P] < .01). The healing rates in patients for whom anti-resorptive agent (ARA) treatment was discontinued and continued were 87.2 and 37.4%, respectively (HR = 1.8, 95% CI = 1.1-3.0, P = .02). In a multiple regression analysis using ARA indication, the therapy method showed a significant association in the MRONJ malignancy group (HR = 2.75, 95% CI = 1.46-5.17, P < .01). CONCLUSION AND RELEVANCE: Operative therapy and ARA discontinuation were associated with better healing rates in MRONJ therapy. However, the choice of therapy for MRONJ should be based on a comprehensive consideration of the patient's condition. ARA discontinuation should be considered an adjunctive measure because of the possibility of adverse events such as fragility fractures and skeletal related events.

Efficacy and Tolerability of Ivabradine for Cardiomyopathy in Patients with Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is an intractable X-linked myopathy caused by dystrophin gene mutations. Patients with DMD suffer from progressive muscle weakness, inevitable cardiomyopathy, increased heart rate (HR), and decreased blood pressure (BP). The aim of this study was to clarify the efficacy and tolerability of ivabradine treatment for DMD cardiomyopathy.A retrospective analysis was performed in 11 patients with DMD, who received ivabradine treatment for more than 1 year. Clinical results were analyzed before (baseline), 6 months after, and 12 months after the ivabradine administration.The initial ivabradine dose was 2.0 ± 1.2 mg/day and the final dose was 5.6 ± 4.0 mg/day. The baseline BP was 95/64 mmHg. A non-significant BP decrease to 90/57 mmHg was observed at 1 month but it recovered to 97/62 mmHg at 12 months after ivabradine administration. The baseline HR was 93 ± 6 bpm and it decreased to 74 ± 12 bpm at 6 months (P = 0.011), and to 77 ± 10 bpm at 12 months (P = 0.008). A linear correlation (y = 2.2x + 5.1) was also observed between the ivabradine dose (x mg/day) and HR decrease (y bpm). The baseline LVEF was 38 ± 12% and it significantly increased to 42 ± 9% at 6 months (P = 0.011) and to 41 ± 11% at 12 months (P = 0.038). Only 1 patient with the lowest BMI of 11.0 kg/m2 and BP of 79/58 mmHg discontinued ivabradine treatment at 6 months, while 1-year administration was well-tolerated in the other 10 patients.Ivabradine decreased HR and increased LVEF without lowering BP, suggesting it can be a treatment option for DMD cardiomyopathy.

Comparison of the inward leakage rate between N95 filtering facepiece respirators and modified surgical masks during the COVID-19 pandemic.

BACKGROUND: Owing to shortage of surgical and N95 filtering facepiece respirators (FFRs) during the COVID-2019 pandemic, various masks were developed to prevent infection. This study aimed to examine the inward leakage rate (ILR) of sealed face masks and modified surgical masks using a quantitative fit test and compared it with the ILR of unmodified N95 FFRs. METHODS: We conducted paired comparisons of ILRs of bent nose-fit wire masks, double masks, and N95 FFRs from October to December 2021. To measure the protective effectiveness of masks, participants wore masks, and the number of particles outside and inside the mask were measured. The ILR was based on the percentage of particles entering the mask using a fit tester. RESULTS: We enrolled 54 participants (20 men and 34 women) in this study. The median ILR for surgical masks without and with a W-shaped bend in the nose-fit wire were 96.44% and 50.82%, respectively. The nose-fit wire adjustment reduced the ILR of surgical masks by a mean of 28.57%, which was significantly lower than the ILR without adjustment (P < 0.001). For double masks, with surgical or polyurethane masks on top of the W-shaped mask, the ILR did not differ significantly from that of N95. Although the filtration performance of double surgical masks matched that of N95 masks, their ILR was notably higher, indicating that double masks do not provide equivalent protection. CONCLUSIONS: Wearing N95 masks alone is effective in many cases. However, surgical mask modifications do not guarantee consistent effectiveness. Properly selected, sealed masks with a good fit overcome leakage, emphasizing their crucial role. Without evidence, mask-wearing may lead to unexpected infections. Education based on quantitative data is crucial for preventing adverse outcomes.

Haemophilia and cardiovascular disease in Japan: Low incidence rates from ADVANCE Japan baseline data.

INTRODUCTION: With the increasing life expectancy of people with haemophilia, the risk of cardiovascular disease (CVD) and thrombotic events has become a growing concern. Longitudinal studies on the incidence and risk factors of CVD in this population are limited, and optimal prevention and treatment strategies are yet to be established. AIM: This study aimed to present the baseline data of a prospective longitudinal study focusing on a subset of Japanese patients with haemophilia, specifically investigated the incidence, risk factors and treatment modalities for CVD and thrombotic diseases in people aged 40 years in Japan over 10 years through the ADVANCE Japan study. METHODS: The ADVANCE Japan study is a prospective multicentre cohort study involving 600 adult individuals with haemophilia A/B aged 40 years in Japan. The primary endpoint was the incidence of CVD, with secondary endpoints encompassing anticoagulant use, mortality rates, and comparison with the general population. RESULTS: Baseline data from the 600 participants revealed that thrombotic events occurred in 13 individuals (2.2%), mostly in those with haemophilia A. Atrial fibrillation was observed in 11 participants (1.8%). Hypertension and dyslipidaemia were identified as the prevalent risk factors. Various prophylactic treatments were employed, and no severe bleeding events were observed during the study period. CONCLUSION: This study provides vital baseline data for a 10-year prospective investigation of CVD and thrombotic disease risk in people with haemophilia. These findings will contribute to refining prevention and treatment approaches and improving patients' quality of life.

Efficacy and safety of intensive downstaging polypectomy (IDP) for multiple duodenal adenomas in patients with familial adenomatous polyposis: a prospective cohort study.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) risk developing multiple duodenal adenomas (MDAs), leading to duodenal cancer and death. We investigated the efficacy and safety of intensive downstaging polypectomy (IDP) for MDAs integrated with new-generation procedures. METHODS: This prospective phase II study, conducted at a tertiary cancer center, enrolled patients with FAP who had MDAs. We performed IDP including cold snare/forceps polypectomy (CSP/CFP) and underwater endoscopic mucosal resection (UEMR). The primary end point was the downstaging of Spigelman stage at 1-year follow-up. RESULTS: 2424 duodenal polyps in 58 patients with FAP underwent IDP, including 2413 CSPs in 57 patients, seven CFPs in one patient, and four UEMRs in four patients. Only one major adverse event was observed (grade 3 hyperamylasemia) without clinical manifestations. We performed additional UEMR, CSP, and CFP for one, 12, and 22 patients, respectively, during initial follow-up. Overall, 55 patients completed protocol examination; the Spigelman stage was significantly reduced at the 1-year follow-up endoscopy (P < 0.001), with downstaging observed in 39 patients (71 %). Among the 26 patients with Spigelman stage IV at initial examination and protocol completion, 23 (88 %) showed downstaging. There was no major change in Spigelman stages from 1-year follow-up esophagogastroduodenoscopy to a median of 37 months (range 3-56). CONCLUSIONS: IDP, including new-generation procedures, showed significant downstaging with acceptable adverse events for MDA in patients with FAP, even those with advanced-stage disease. Lesion selection for different resection techniques may be important for suitable and sustainable management of MDA in patients with FAP.

Exploratory Research on Determinants of Place of Death in a Large-scale Cohort Study: The JPHC Study.

BACKGROUND: The place of death and related factor, such as diseases, symptoms, family burden, and cost, has been examined, but social background and lifestyle were not considered in most studies. Here, we assessed factors that are associated with the place of death using the largest cohort study in Japan. METHODS: A total of 17,781 deaths from the cohort study were assessed. The study database was created from the Japan Public Health Center-based Prospective Study (JPHC Study), in which demographic data were collected from Japanese Vital Statistics. Adjusted odds ratios for home death were calculated using logistic regression. RESULTS: Multivariate analysis adjusted for various factors showed that unmarried status (odds ratio [OR] 2.4; 95% confidence interval [CI], 2.0-2.9), unemployed male (OR 1.3; 95% CI, 1.1-1.5), and high drinking level in male (OR 1.3; 95% CI, 1.1-1.6) were associated with home death. Regarding the cause of death, cardiovascular disease (OR 3.3; 95% CI, 2.9-3.8), cerebrovascular disease (OR 1.9; 95% CI, 1.6-2.2), and external factors (OR 4.1; 95% CI, 3.5-4.8) were significantly associated with home death, compared with cancer. The risk of death at home was significantly higher among unmarried subjects stratified by cause of death (cardiovascular disease: OR 3.2; 95% CI, 2.2-4.7; cerebrovascular disease: OR :5.1; 95% CI, 2.9-9.1; respiratory disease: OR 3.4; 95% CI, 1.6-7.6; and external factors: OR 2.3; 95% CI, 1.4-3.7), but for cancer, the risk of death at home tended to be higher among married participants. CONCLUSION: This study found that various factors are associated with home death using the largest cohort study in Japan. There is a high possibility of home deaths in people with fewer social connections and in those with diseases leading to sudden death.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Identification of microRNA-96-5p as a postoperative, prognostic microRNA predictor in nonviral hepatocellular carcinoma.

AIM: The microRNA (miR) clusters miR-183/96/182 and miR-217/216a/216b are significantly upregulated in nonviral hepatocellular carcinoma (NBNC-HCC). Here, we investigate the impact of each member of these clusters on the clinical outcome of NBNC-HCC and analyze the antitumor effects of miR-96-5p. METHODS: The association between recurrence-free survival of 111 NBNC-HCC patients and the levels of miR-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, miR-216a-5p, and miR-216b-5p in tumor and adjacent tissues was investigated. The impact of miR-96-5p on apoptosis and invasion of a hepatoma cell line, HepG2, was investigated by cell counting, Transwell assay, and flow cytometry, respectively. RESULTS: MicroRNA-183-5p, miR-96-5p, miR-182-5p, miR-217-5p, and miR-216b-5p were significantly upregulated in tumor tissues compared to the adjacent tissues (p = 0.0005, p = 0.0030, p = 0.0002, p = 0.0011, and p = 0.0288, respectively). By multivariate Cox regression analysis, high tumor/adjacent ratios of miR-182-5p (p = 0.007) and miR-217-5p (p = 0.008) were associated with poor recurrence-free survival. In contrast, a low tumor/adjacent ratio of miR-96-5p (p < 0.001) was associated with poor recurrence-free survival. It suggested that further upregulation of miR-96-5p in tumors might have an inhibitory effect on recurrence. Transfection of miR-96-5p mimic significantly induced apoptosis of HepG2 cells, in association with downregulation of Nucleophosmin 1 (NPM1) and a decrease of phosphorylated AKT protein. Interestingly, simultaneous knockdown of the NPM1 and AKT genes induced apoptosis. MicroRNA-96-5p also suppressed proliferation and invasion, which inhibited epithelial-to-mesenchymal transition of HCC cells. CONCLUSION: MicroRNA-96-5p as a tumor suppressor would be valuable to stratify NBNC-HCC patients at high risk of recurrence.

Prevalence of Myofascial Pain Syndrome and Efficacy of Trigger Point Injection in Patients with Incurable Cancer: A Multicenter, Prospective Observational Study (MyCar Study).

OBJECTIVE: Myofascial pain syndrome (MPS) is caused by overload or disuse of skeletal muscles. Patients with cancer are often forced to restrict their movement or posture for several reasons. The study was conducted to investigate the prevalence and risks of MPS in patients with incurable cancer. The efficacy of trigger point injection (TPI) was also explored. METHODS: This was a multicenter, prospective observational study. Patients with incurable cancer who started receiving specialist palliative care were enrolled. We investigated the MPS in this population and accompanying risk factors for restricting body movement. Pre- and post-TPI pain was also evaluated using a Numerical Rating Scale (NRS) in patients who received TPI. The primary outcome was the prevalence of MPS. RESULTS: A total of 101 patients were enrolled from five institutions in Japan. Most of the patients (n = 94, 93.1%) had distant metastases, and half of the patients (50, 49.5%) received anticancer treatment. Thirty-nine (38.6%) patients had MPS lesions at 83 sites. Multivariate analysis revealed that the significant risk factor for MPS was poor Performance Status (PS) (odds ratio 3.26; 95% confidence interval [CI] 1.18-9.02, P = .023). We performed TPI for 40 out of 83 MPS lesions. Mean NRS for MPS before TPI was 7.95, which improved to 4.30 after TPI (P < .001). CONCLUSIONS: MPS was common in patients with incurable cancer and the risk factor identified in this study was poor performance status. TPI could be a treatment option.

Comparative whole-genome and proteomics analyses of the next seed bank and the original master seed bank of MucoRice-CTB 51A line, a rice-based oral cholera vaccine.

BACKGROUND: We have previously developed a rice-based oral vaccine against cholera diarrhea, MucoRice-CTB. Using Agrobacterium-mediated co-transformation, we produced the selection marker-free MucoRice-CTB line 51A, which has three copies of the cholera toxin B subunit (CTB) gene and two copies of an RNAi cassette inserted into the rice genome. We determined the sequence and location of the transgenes on rice chromosomes 3 and 12. The expression of alpha-amylase/trypsin inhibitor, a major allergen protein in rice, is lower in this line than in wild-type rice. Line 51A was self-pollinated for five generations to fix the transgenes, and the seeds of the sixth generation produced by T5 plants were defined as the master seed bank (MSB). T6 plants were grown from part of the MSB seeds and were self-pollinated to produce T7 seeds (next seed bank; NSB). NSB was examined and its whole genome and proteome were compared with those of MSB. RESULTS: We re-sequenced the transgenes of NSB and MSB and confirmed the positions of the three CTB genes inserted into chromosomes 3 and 12. The DNA sequences of the transgenes were identical between NSB and MSB. Using whole-genome sequencing, we compared the genome sequences of three NSB with three MSB samples, and evaluated the effects of SNPs and genomic structural variants by clustering. No functionally important mutations (SNPs, translocations, deletions, or inversions of genic regions on chromosomes) between NSB and MSB samples were detected. Analysis of salt-soluble proteins from NSB and MSB samples by shot-gun MS/MS detected no considerable differences in protein abundance. No difference in the expression pattern of storage proteins and CTB in mature seeds of NSB and MSB was detected by immuno-fluorescence microscopy. CONCLUSIONS: All analyses revealed no considerable differences between NSB and MSB samples. Therefore, NSB can be used to replace MSB in the near future.

A genome-wide association study identifying SVEP1 variant as a predictor of response to tolvaptan for cirrhotic ascites.

BACKGROUND & AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. METHODS: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. RESULTS: Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

Superiority of OxyMaskTM with less carbon dioxide rebreathing in children.

Despite the growing importance of oxygen-delivery devices worldwide, there are only a few reports of physiological data on various oxygen masks in children. The possibility of carbon dioxide (CO2) rebreathing has been a prevalent concern with the use of oxygen-delivery devices. OxyMask KidTM (Southmedic Inc. Canada; hereafter OxyMask) is expected to reduce CO2 rebreathing even at low oxygen flow rates because of its structural features. Biological data using OxyMask in children have not been well investigated. Measured respiratory parameters of OxyMask with those of a simple oxygen mask in healthy children were compared. Ten subjects were enrolled, with a median age of 5.4 years. All subjects used both OxyMask and a simple oxygen mask. The fraction of inspiratory oxygen (FIO2), partial pressure of inspiratory CO2 (PICO2), and partial pressure of end-tidal CO2 were measured using a sidestream gas-sampling monitor in all subjects. The oxygen flow rate was set at 1, 3, 5, and 10 L/min. FIO2 levels were higher with OxyMask than those with the simple oxygen mask at 3 L/min of oxygen. PICO2 levels were significantly lower with OxyMask than those with the simple oxygen mask (1.5 mmHg vs. 3.7 mmHg at 1 L/min, P = 0.005; 1.0 mmHg vs. 2.7 mmHg at 3 L/min, P = 0.005, respectively), whereas PICO2 levels were higher at low oxygen flow rates with both masks.Conclusion: Our results showed that higher FIO2 and less CO2 rebreathing were achieved with OxyMask than those with a simple oxygen mask at low flow rates of oxygen in healthy children. What is Known: • OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. • Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: • Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children.

Changes in survival and causes of death among people living with HIV: Three decades of surveys from Tokyo, one of the Asian metropolitan cities.

INTRODUCTION: Survival among people living with HIV (PLWH) has dramatically improved in the antiretroviral therapy (ART) era. This is the first study in Asia to describe three decades of surveys on survival and causes of death among PLWH. METHODS: We included 1121 HIV-infected patients, categorized into three period groups according to date of first visit: 1986-1996 (Pre-ART); 1997-2007 (Early-ART); and 2008-2018 (Late-ART). RESULTS: Ten-year all-cause mortality has reduced from Pre-ART (49.6/1000 person-years) to Late-ART (6.3/1000 person-years). Mortality for AIDS-defining illnesses (ADIs) has also reduced from Pre-ART (34.4/1000 person-years) to Late-ART (2.9/1000 person-years), and mortality for non-ADIs has reduced from Pre-ART (11.7/1000 person-years) to Late-ART (2.9/1000 person-years). In the ART-era, deaths from non-AIDS-defining malignancies and unnatural events including suicide represented the majority of non-ADI-related deaths and mortality rates of non-AIDS defining malignancies and unnatural cause event were not different between each group (3.4, 1.9 and 2.5/1000 person-years). Crude cumulative survival improved over the study period, and 10-year survival ratios of HIV-infected patients to the general Japanese population approached 1.00, from Pre-ART (0.66) to Late-ART (0.99). Even in the Late-ART period, survival remained lower in patients with a history of ADIs than in those without, but the difference in 5-year mortality between these groups has shrunk in the Late-ART compared to the Pre-ART. CONCLUSIONS: Mortality for ADIs and non-ADIs in PLWH has reduced in the Early-ART and Late-ART. To improve survival for PLWH further, early HIV detection and treatment and good management of non-AIDS-defining malignancies and mental disorders are needed. (248/250).

Correction: Importance of gastric cancer for the diagnosis and surveillance of Japanese Lynch syndrome patients.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Long-term eradication of extranodal natural killer/T-cell lymphoma, nasal type, by induced pluripotent stem cell-derived Epstein-Barr virus-specific rejuvenated T cells in vivo.

Functionally rejuvenated induced pluripotent stem cell (iPSC)-derived antigen-specific cytotoxic T lymphocytes (CTL) are expected to be a potent immunotherapy for tumors. When L-asparaginase-containing standard chemotherapy fails in extranodal natural killer/T-cell lymphoma, nasal type (ENKL), no effective salvage therapy exists. The clinical course then is miserable. We demonstrate prolonged and robust eradication of ENKL in vivo by Epstein-Barr virus-specific iPSC-derived antigen-specific CTL, with iPSC-derived antigen-specific CTL persisting as central memory T cells in the mouse spleen for at least six months. The anti-tumor response is so strong that any concomitant effect of the programmed cell death 1 (PD-1) blockade is unclear. These results suggest that long-term persistent Epstein-Barr virus-specific iPSC-derived antigen-specific CTL contribute to a continuous anti-tumor effect and offer an effective salvage therapy for relapsed and refractory ENKL.

Multiloop as a novel traction method in accelerating colorectal endoscopic submucosal dissection.

BACKGROUND AND AIMS: Traction methods have been reported to speed up endoscopic submucosal dissection (ESD). We used the multiloop (M-loop) method as a traction method for colorectal ESD and recorded the submucosal dissection time (SDT) and submucosal dissection speed (SDS). METHODS: From January to August 2018, we used the M-loop method for colorectal ESD procedures and timed the duration and recorded the outcomes. Two experts and eight nonexperts performed the procedures, which were carried out at a tertiary endoscopic center in Japan. RESULTS: A total of 50 patients were treated by colorectal ESD using the M-loop method. The mean SDT was 42.1 ± 4.16 minutes and the mean SDS was 28.0 ± 2.89 mm2/minutes. The mean SDS was 38.9 ± 6.9 mm2/minutes for experts and 25.3 ± 3.1 mm2/minutes for nonexperts. En bloc resection was achieved in 100% of cases. There were 3 adverse events and unfavorable outcomes. CONCLUSIONS: Traction by the M-loop method improved SDS in colorectal ESD. The method can be an effective tool to assist colorectal ESD. Further evaluation of the usefulness of the M-loop method is required in direct comparison with conventional ESD.

High Prevalence of Left Ventricular Non-Compaction and Its Effect on Chemotherapy-Related Cardiac Dysfunction in Patients With Hematological Diseases.

BACKGROUND: Recent progress in chemotherapy has prolonged the survival of patients with hematological diseases, but has also increased the number of patients with chemotherapy-related cardiac dysfunction (CTRCD). However, the causes of individual variations and risk factors for CTRCD have yet to be fully elucidated.Methods and Results:Consecutive echocardiograms of 371 patients were retrospectively evaluated for the presence of left ventricular (LV) non-compaction (LVNC). Individual LV ejection fraction (LVEF) outcome estimates were made using bivariate linear regression with log-transformed duration Akaike information criterion (AIC) model fitting. The prevalence of LVNC was 6-fold higher in patients with hematological diseases than in those with non-hematological diseases (12% vs. 2%; risk ratio 6.1; 95% confidence interval [CI] 2.0, 18.2). Among patients with hematological diseases, the ratio of myeloid diseases was significantly higher in the group with LVNC (P=0.031). Deterioration of LVEF was more severe in patients with than without LVNC (-14.4 percentage points/year [95% CI -21.0, -7.9] vs. -4.6 percentage points/year [95% CI -6.8, -2.4], respectively), even after multivariate adjustment for baseline LVEF, background disease distributions, cumulative anthracycline dose, and other baseline factors. CONCLUSIONS: LVNC is relatively prevalent in patients with hematological diseases (particularly myeloid diseases) and can be one of the major risk factors for CTRCD. Detailed cardiac evaluations including LVNC are recommended for patients undergoing chemotherapy.

Endovascular Aortic Aneurysm Repair without Type 2 Endoleak Using Concomitant N-Butyl-2-Cyanoacrylate Injection into the Abdominal Aortic Aneurysm Sac.

BACKGROUND: The aim of this study was to evaluate our new method to occlude target lumber arteries using N-butyl-2-cyanoacrylate (NBCA) during endovascular aneurysm repair (EVAR) for prevention of type 2 endoleak (T2E). METHODS AND RESULTS: Between 2013 and 2018, 176 patients who underwent EVAR for abdominal aortic aneurysm (AAA) were reviewed. Starting from October 2015, 83 patients (treatment group) underwent NBCA injection into the aneurysmal sac during EVAR. The incidence of T2E at 7 days and AAA sac diameter 12 months after EVAR were compared with those of the control group comprising 93 consecutive patients who underwent EVAR alone before 2015. The incidence of T2E at 7 days was significantly lower in the treatment group (2.4%) than in the control group (22.6%) (P < 0.001). AAA sac diameter at 12 months in the treatment group had a mean decrease of 6.6 mm as compared with the mean 4.4 mm in the control group (P = 0.026). In multivariate analysis, NBCA injection was significantly related to the reduction of incidence of T2E at 7 days (odds ratio = 11.8, P < 0.001) and a decrease in AAA sac diameter at 12 months (P < 0.001). There was no NBCA injection-related complication and reintervention in the treatment group. CONCLUSIONS: NBCA injection might be safe and useful to reduce the incidence of T2Es and to prevent AAA sac expansion.