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BACKGROUND: Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. CONCLUSIONS: FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

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Aspiration pneumonia can occur in perioperative and older patients, and various oral care methods have been used to prevent it. To validate the effective oral care methods, measuring bacterial counts before and after oral care is necessary. However, isolating and quantifying viable bacteria from those that are inactivated by agents used in oral care is not possible. In this study, we developed a novel method, Delayed real-time PCR (DR-PCR), that can quantify only viable bacteria from mixed samples of viable and dead bacteria. This method takes advantage of the fact that dead bacteria do not grow but viable bacteria do. When the samples were incubated in a liquid medium for 4 hours, the higher the percentage of viable bacteria, the higher the rate of increase in the number of bacteria. This method showed that povidone­iodine mouthwashing reduced the number of viable bacteria to approximately 1/4 of that before mouthwashing. Although DR-PCR is slightly more time consuming than real-time PCR, it is effective for studying changes in bacterial counts before and after oral care.

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Background/purpose: Denosumab is used to treat bone metastases from malignant tumors. Unlike bisphosphonates, denosumab is not deposited in the bone; thus, withdrawal for a relatively short period would help recovery from osteoclast suppression. This study investigated the relationship between drug holidays and recovery from osteoclast suppression. Materials and methods: Seven patients who received high-dose denosumab and underwent segmental mandibulectomy for medication-related osteonecrosis of the jaw were enrolled in this study. Osteoclast suppression (+) was defined as the absence of cathepsin K-positive cells or cathepsin K-positive mononuclear or small multinucleated cells observed on the bone surface of both mesial and distal specimens. When normal osteoclasts were found, osteoclast suppression was defined as (-); when both suppressed cathepsin K-positive cells and normal morphological osteoclasts were found, it was defined as (±). Results: Osteoclast suppression was: (+) in four patients, three without a drug holiday and one with a 9-month drug holiday; (±) in one patient with an 8-month drug holiday, and (-) in two patients with drug holidays for 13 and 20 months. Conclusion: These findings suggest that a long-term drug holiday, such as 12 months, is required for recovery from osteoclast suppression in patients with cancer receiving high-dose denosumab.

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Induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) hold great promise as a cell source for transplantation into injured tissues to alleviate inflammation. However, the therapeutic efficacy of iMSC transplantation for ischemic stroke remains unknown. In this study, we evaluated the therapeutic effects of iMSC transplantation on brain injury after ischemia-reperfusion using a rat transient middle cerebral artery occlusion model and compared its therapeutic efficacy with that of bone marrow mesenchymal stem cells (BMMSCs). We showed that iMSCs and BMMSCs reduced infarct volumes after reperfusion and significantly improved motor function on days 3, 7, 14, 28, and 56 and cognitive function on days 28 and 56 after reperfusion compared with the vehicle group. Furthermore, immunological analyses revealed that transplantation of iMSCs and BMMSCs inhibited microglial activation and expression of proinflammatory cytokines and suppressed oxidative stress and neuronal cell death in the cerebral cortex at the ischemic border zone. No difference in therapeutic effect was observed between the iMSC and BMMSC groups. Taken together, our results demonstrate that iMSC therapy can be a practical alternative as a cell source for attenuation of brain injury and improvement of neurological function because of the unlimited supply of uniform therapeutic cells.

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Medication-related osteonecrosis of the jaw (MRONJ) is a refractory osteonecrosis caused by antiresorptive agents such as bisphosphonate and denosumab (DMB). In MRONJ surgery, computed tomography (CT) is generally used to determine the extent of bone resection. However, in some recent MRONJ cases, no abnormal findings were detected on CT. Therefore, we aimed to clarify the characteristics of MRONJ without osteolysis. This retrospective and observational study included 18 patients diagnosed with MRONJ between October 2020 and October 2022 at Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center. In four of 18 patients with MRONJ, no abnormal findings such as osteolysis, separation of sequestrum, and periosteal reaction were observed on CT images at the first visit. All four patients with non-osteolytic MRONJ had malignant tumors and received high-dose DMB, and in the four patients there were no preceding dental infections such as apical lesions or periodontal disease and the trigger of MRONJ was unknown. Surgery was performed in three of the four patients. The extent of bone resection was determined using magnetic resonance imaging and intraoperative gross findings. In the future, it is necessary to establish a method for diagnosing non osteolytic MRONJ and determining the extent of bone resection.

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BACKGROUND: To investigate whether ultra-early recombinant tissue-plasminogen activator (rt-PA) administration can improve patient outcomes on mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO). METHODS: Participants comprised rt-PA-eligible 204 patients with internal carotid artery or middle cerebral artery occlusion in the SKIP trial, who were randomly assigned to receive mechanical thrombectomy alone or combined intravenous thrombolysis (rt-PA: alteplase at 0.6 mg/kg) plus mechanical thrombectomy. We assessed associations between onset-to-puncture time and onset-to-rt-PA administration time and frequency of favorable outcome at 90 days and any intracerebral hemorrhage (ICH) at 36 h after onset. RESULTS: As a cut-off onset-to-puncture time for favorable outcome, receiver operating characteristic curves defined 2.5 h (57% sensitivity, 62% specificity). For onset-to-puncture times ≤2.5 h and > 2.5 h, frequencies of favorable outcomes were 72% and 63% (p = 0.402) in patients with rt-PA therapy and 44% and 58% (p = 0.212) in patients without rt-PA therapy, respectively. In terms of onset-to-rt-PA administration time, frequencies of favorable outcomes among patients with ultra-early rt-PA administration at ≤100, >100 min after onset, and without rt-PA therapy with onset-to-puncture time ≤ 2.5 h, and with and without rt-PA therapy with onset-to-puncture time > 2.5 h were 84% and 64%, 63%, and 44% and 58%, respectively (p = 0.025). Frequencies of any ICH among those patients were 37% and 32%, 32%, and 63% and 40%, respectively (p = 0.006). CONCLUSION: Ultra-early rt-PA administration should improve patient outcomes on mechanical thrombectomy among patients with LVO. Relatively late rt-PA administration might increase the frequency of any ICH.

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BACKGROUND: Drug-coated balloon (DCB) became a potential treatment option for patients with acute coronary syndrome (ACS); however, factors associated with target lesion failure (TLF) remain uncertain. METHODS: This retrospective, multicentre, observational study included consecutive ACS patients who underwent optical coherence tomography (OCT)-guided DCB treatment. Patients were divided into two groups according to the occurrence of TLF, a composite of cardiac death, target vessel-related myocardial infarction, and ischemia-driven target lesion revascularisation. RESULTS: We enrolled 127 patients in this study. During the median follow-up period of 562 (IQR: 342-1164) days, 24 patients (18.9%) experienced TLF, and 103 patients (81.1%) did not. The cumulative 3-year incidence of TLF was 22.0%. The cumulative 3-year incidence of TLF was the lowest in patients with plaque erosion (PE) (7.5%), followed by those with rupture (PR) (26.1%) and calcified nodule (CN) (43.5%). Multivariable Cox regression analysis revealed that plaque morphology was independently associated with TLF on pre-PCI (percutaneous coronary intervention) OCT, and residual thrombus burden (TB) was positively associated with TLF on post-PCI OCT. Further stratification by post-PCI TB revealed a comparable incidence of TLF in patients with PR (4.2%) to that of PE if the culprit lesion had a smaller post-PCI TB than the cut-off value (8.4%). TLF incidence was high in patients with CN, regardless of TB size on post-PCI OCT. CONCLUSIONS: Plaque morphology was strongly associated with TLF for ACS patients after DCB treatment. Residual TB post-PCI might be a key determinant for TLF, especially in patients with PR.

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OBJECTIVES: This study aimed to investigate the characteristics of patients who report improvement in quality of life (QOL) related to urinary status after undergoing robot-assisted radical prostatectomy (RARP) for localized prostate cancer. METHODS: We retrospectively reviewed the patients who underwent RARP between May 2010 and May 2021 at our institution and were preoperatively unsatisfied with their urinary status. Patients were grouped as Group 1 (improved patients: "satisfied" with urinary status based on international prostate symptom score QOL [IPSS-QOL] = 0-2 at 12 months after RARP) and Group 2 (unimproved group: "unsatisfied"-IPSS-QOL 3-6). Additionally, the Expanded Prostate Cancer Index Composite (EPIC) urinary subdomains (urinary function, urinary bother [UB], urinary incontinence, and urinary irritation/obstruction [UIR]) and IPSS were evaluated preoperatively and till 12 months after RARP. RESULTS: Of the 237 patients, 72 (30.4%) were Group 1, and 165 (69.6%) were Group 2. Only UB and UIR improved at 12 months after RARP in Group 1, while other EPIC urinary subdomains remained unimproved at 12 months in both groups. On the other hand, IPSS improved at 12 months in both groups. Univariate and multivariate analysis revealed that the nerve-sparing, preoperative low IPSS (<11 vs. ≥11), and low IPSS-QOL (3 vs. 4-6) were associated with improvement in urinary status-related QOL (p < 0.05). CONCLUSIONS: Improvement in UB and UIR are important factors to ascertain improvement in urinary status-related QOL after RARP. Nerve-sparing and preoperative IPSS/IPSS-QOL values are useful predictors of this improvement.

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BACKGROUND: Diffusion-weighted imaging-Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS) has been used to estimate infarct core volume in acute stroke. However, the same and indiscriminate score deduction for punctate or confluent DWI high-intensity lesion might lead to variation in performance. AIMS: To develop and evaluate a differential detailed DWI-ASPECTS method in comparison with the conventional DWI-ASPECTS in core infarct volume measurement and clinical outcome prediction. METHODS: We retrospectively recruited patients with acute ischemic stroke (AIS) treated with endovascular treatment between April 2013 and October 2019. In differential detailed DWI-ASPECTS, restricted diffusion lesion that was punctate or less than half of a cortical region (M1-M6) would not lead to subtraction of point. A favorable outcome was modified Rankin Scale score ⩽2 at 90 days after stroke onset. RESULTS: Among 298 AIS patients, mean age was 75 years (interquartile range (IQR) 67-82), and 194 patients (65%) were males. Mean infarct core volume was 11 mL (IQR 3-37). Overall, the score by detailed DWI-ASPECTS was significantly higher than conventional DWI-ASPECTS (8 (7-9) vs. 7 (5-9); P < 0.01). The detailed DWI-ASPECTS resulted in a higher correlation coefficient (r) for core infarct volume estimation than the conventional DWI-ASPECTS (r = 0.832 vs. 0.773; P < 0.01). Upon re-classification of those scored ⩽6 in conventional DWI-ASPECTS (n = 134) by detailed DWI-ASPECTS, the rate of favorable outcome in patients with detailed DWI-ASPECTS >6 was significantly higher than those with ⩽6 (29 (48%) vs. 14 (19%); P < 0.01). CONCLUSIONS: Detailed DWI-ASPECTS appeared to provide a more accurate infarct core volume measurement and clinical outcome correlation than conventional DWI-ASPECTS among AIS patients treated with endovascular therapy.

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Being able to change cell fate after differentiation highlights the remarkable developmental plasticity of plant cells. Recent studies show that phytohormones, such as auxin and cytokinin, promote cell cycle reactivation, a critical first step to reprogramme mitotically inactive, differentiated cells into organogenic stem cells. Accumulating evidence suggests that wounding provides an additional cue to convert the identity of differentiated cells by promoting the loss of existing cell fate and/or acquisition of new cell fate. Differentiated cells can also alter cell fate without undergoing cell division and in this case, wounding and phytohormones induce master regulators that can directly assign new cell fate.

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BACKGROUND: Early control of elevated blood pressure is the most promising treatment for acute intracerebral haemorrhage. We aimed to establish whether implementing a goal-directed care bundle incorporating protocols for early intensive blood pressure lowering and management algorithms for hyperglycaemia, pyrexia, and abnormal anticoagulation, implemented in a hospital setting, could improve outcomes for patients with acute spontaneous intracerebral haemorrhage. METHODS: We performed a pragmatic, international, multicentre, blinded endpoint, stepped wedge cluster randomised controlled trial at hospitals in nine low-income and middle-income countries (Brazil, China, India, Mexico, Nigeria, Pakistan, Peru, Sri Lanka, and Viet Nam) and one high-income country (Chile). Hospitals were eligible if they had no or inconsistent relevant, disease-specific protocols, and were willing to implement the care bundle to consecutive patients (aged ≥18 years) with imaging-confirmed spontaneous intracerebral haemorrhage presenting within 6 h of the onset of symptoms, had a local champion, and could provide the required study data. Hospitals were centrally randomly allocated using permuted blocks to three sequences of implementation, stratified by country and the projected number of patients to be recruited over the 12 months of the study period. These sequences had four periods that dictated the order in which the hospitals were to switch from the control usual care procedure to the intervention implementation of the care bundle procedure to different clusters of patients in a stepped manner. To avoid contamination, details of the intervention, sequence, and allocation periods were concealed from sites until they had completed the usual care control periods. The care bundle protocol included the early intensive lowering of systolic blood pressure (target <140 mm Hg), strict glucose control (target 6·1-7·8 mmol/L in those without diabetes and 7·8-10·0 mmol/L in those with diabetes), antipyrexia treatment (target body temperature ≤37·5°C), and rapid reversal of warfarin-related anticoagulation (target international normalised ratio <1·5) within 1 h of treatment, in patients where these variables were abnormal. Analyses were performed according to a modified intention-to-treat population with available outcome data (ie, excluding sites that withdrew during the study). The primary outcome was functional recovery, measured with the modified Rankin scale (mRS; range 0 [no symptoms] to 6 [death]) at 6 months by masked research staff, analysed using proportional ordinal logistic regression to assess the distribution in scores on the mRS, with adjustments for cluster (hospital site), group assignment of cluster per period, and time (6-month periods from Dec 12, 2017). This trial is registered at Clinicaltrials.gov (NCT03209258) and the Chinese Clinical Trial Registry (ChiCTR-IOC-17011787) and is completed. FINDINGS: Between May 27, 2017, and July 8, 2021, 206 hospitals were assessed for eligibility, of which 144 hospitals in ten countries agreed to join and were randomly assigned in the trial, but 22 hospitals withdrew before starting to enrol patients and another hospital was withdrawn and their data on enrolled patients was deleted because regulatory approval was not obtained. Between Dec 12, 2017, and Dec 31, 2021, 10 857 patients were screened but 3821 were excluded. Overall, the modified intention-to-treat population included 7036 patients enrolled at 121 hospitals, with 3221 assigned to the care bundle group and 3815 to the usual care group, with primary outcome data available in 2892 patients in the care bundle group and 3363 patients in the usual care group. The likelihood of a poor functional outcome was lower in the care bundle group (common odds ratio 0·86; 95% CI 0·76-0·97; p=0·015). The favourable shift in mRS scores in the care bundle group was generally consistent across a range of sensitivity analyses that included additional adjustments for country and patient variables (0·84; 0·73-0·97; p=0·017), and with different approaches to the use of multiple imputations for missing data. Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16·0% vs 20·1%; p=0·0098). INTERPRETATION: Implementation of a care bundle protocol for intensive blood pressure lowering and other management algorithms for physiological control within several hours of the onset of symptoms resulted in improved functional outcome for patients with acute intracerebral haemorrhage. Hospitals should incorporate this approach into clinical practice as part of active management for this serious condition. FUNDING: Joint Global Health Trials scheme from the Department of Health and Social Care, the Foreign, Commonwealth & Development Office, and the Medical Research Council and Wellcome Trust; West China Hospital; the National Health and Medical Research Council of Australia; Sichuan Credit Pharmaceutic and Takeda China.

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We report a unique phototunable cell killing technique using diarylethene molecules as photo-isomerizing-molecular switches. These molecules were delivered to DNA in the cell nucleus due to closed-form generated by UV light, and then blue light triggered cell killing. A UV light irradiation switches the open form, having no DNA intercalation activity, to the closed form to induce intercalation in DNA. This isomer, thus prepared ready for the action, exerts photocytotoxicity upon the subsequent blue light irradiation. Molecular biological analysis clarifies that photocytotoxicity is due to DNA double-strand breaks. Since cell death is observed only when irradiated with light where both the open- and closed-ring isomers have absorption, the possible mechanism of cell death is assumed to be due to the repeated photocyclization and photocycloreversion reactions of the diarylethene molecules, which induce irreparable damage to DNA. This unique photo-controllable action in a cell system can provide the basis of a novel scheme of phototherapy.

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This study determined the predictive accuracy of optical frequency domain imaging (OFDI) on debulking effects of rotational atherectomy (RA) and compared the predictive accuracy of OFDI catheter-based with Rota wire-based prediction methods. This prospective, single-center, observational study included 55 consecutive patients who underwent OFDI-guided RA. On pre-RA OFDI images, a circle, identical to the Rota burr was drawn at the center of the OFDI catheter (OFDI catheter-based prediction method) or wire (wire-based prediction method). The area overlapping the vessel wall was defined as the predicted ablation area (P-area). The actual ablated area (A-area) was measured by superimposing the OFDI images before and after RA. The overlapping P-area and A-area were defined as overlapped ablation area (O-area), and the predictive accuracy was evaluated by %Correct area (O-area/P-area) and %Error area (A-area - O-area/A-area). The median %Correct and %Error areas were 47.8% and 41.6%, respectively. Irrelevant ablation (low %Correct-/high % Error areas) and over ablation (high %Correct-/high % Error areas) were related to deep vessel injury and intimal flap outside the P-area. The predictive accuracy was better in the OFDI catheter-based prediction method than the wire-based prediction method in the cross sections where the OFDI catheter and wire came in contact. However, it was better in the latter than the former where the OFDI catheter and wire were not in contact. OFDI-based simulation of the RA effect is feasible though accuracy may be affected by the OFDI catheter and wire position. OFDI-based simulation of RA effect might reduce peri-procedural complications during RA.

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BACKGROUND: Advanced lung cancer inflammation index (ALI) is reported to be a prognosticator in various cancer patients with chemotherapy. However, the clinical impact of the ALI on treatment strategies in metastatic colorectal cancer (mCRC) patients remains unclear. METHODS: A total of 356 patients, who received first-line chemotherapy for mCRC between April 2005 and November 2019 in a single institution, were retrospectively enrolled. The association of pretreatment ALI (calculated as follows: BMI × albumin value/neutrophil-to-lymphocyte ratio) status with clinicopathological factors and patient survival outcome was analyzed, using subgroup analysis. RESULTS: The ALI-low cases were significantly associated with female sex, more synchronous metastasis, multiple metastatic sites, less primary tumor resection, less liver resection after chemotherapy, and poor overall survival (OS). A multivariate Cox proportional hazards analysis clarified that the ALI-low status was independently associated with poor OS (HR: 1.78, 95% CI 1.27-2.48, P = 0.001), in addition to right side tumor, multiple metastatic sites, and the non-performance of liver resection after chemotherapy. A subgroup analysis revealed that primary tumor resection and the resection of liver metastases after chemotherapy could not improve the prognosis of ALI-low cases in comparison with ALI-high cases, and the type of first-line chemotherapy did not significantly affect the association between the prognosis and the ALI status. CONCLUSION: ALI comprehensively evaluates the prognostic host status and is a reliable prognosticator for the mCRC patients with chemotherapy. Calculating pretreatment ALI may serve as a cost-effective and easily available tool for constructing treatment strategies.

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INTRODUCTION: Aspiration pneumonia, an important issue for the older adults, is caused by an increase in pathogenic microorganisms in the saliva, aspiration, and weakened host immunity. Recently, decreased tongue pressure has been reported to be associated with dysphagia. This study aimed to investigate the relationship between decreased tongue pressure and the number of bacteria in the saliva of the older adults requiring long-term care. METHODS: This cross-sectional study involved 95 older adults requiring long-term care in a facility or at home, eating orally, and who could understand the instructions for measuring tongue pressure. Sex, age, slowness, weakness, shrinking, exhaustion, low activity, number of teeth, functional teeth unit, denture use, oral hygiene, tongue coating index, dry mouth, tongue pressure, and number of bacteria in the saliva were examined. Bacterial counts were analyzed by real-time PCR for total bacteria, total streptococci, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Porphyromonas gingivalis, and Candida albicans. RESULTS: Multiple regression analysis showed that poor oral hygiene and decreased tongue pressure were independent risk factors for increased bacteria in the saliva. Decreased tongue pressure is significantly correlated with an increased number of total bacteria and the presence of P. gingivalis. DISCUSSION/CONCLUSION: Our results suggest that tongue pressure not only maintains the swallowing function but also prevents the increase of bacteria in the saliva of older adults requiring long-term care.

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AIMS: High levels of high-density lipoprotein cholesterol (HDL-C) are not necessarily effective in preventing atherosclerotic cardiovascular disease, and cholesterol efflux capacity (CEC) has attracted attention regarding HDL functionality. We aimed to elucidate whether drinking habits are associated with CEC levels, while also paying careful attention to confounding factors including serum HDL-C levels, other life style factors, and rs671 (＊2), a genetic polymorphism of the aldehyde dehydrogenase 2 (ALDH2) gene determining alcohol consumption habit. METHODS: A cross-sectional study was performed in 505 Japanese male subjects who were recruited from a health screening program. Associations of HDL-C and CEC levels with drinking habits and ALDH2 genotypes were examined. RESULTS: The genotype frequencies of ALDH2 ＊1/＊1 (homozygous wild-type genotype), ＊1/＊2 and ＊2/＊2 (homozygous mutant genotype) were 55%, 37% and 8%, respectively. Both HDL-C and CEC levels were higher in ALDH2 ＊1/＊1 genotype carriers than in ＊2 allele carriers. Although HDL-C levels were higher in subjects who had a drinking habit than in non-drinkers, CEC levels tended to be lower in subjects with ≥ 46 g/day of alcohol consumption than in non-drinkers. Furthermore, CEC levels tended to be lower in ALDH2 ＊1/＊1 genotype carriers with a drinking habit of ≥ 46 g/day than non-drinkers, while for ＊2 allele carriers, CEC levels tended to be lower with a drinking habit of 23-45.9 g/day compared to no drinking habit. CONCLUSIONS: Our results suggest that heavy drinking habits may tend to decrease CEC levels, and in the ALDH2 ＊2 allele carriers, even moderate drinking habits may tend to decrease CEC levels.

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BACKGROUND: Experimental studies suggest that self-expanding metal stents (SEMSs) enhance the aggressive behavior of obstructive colorectal cancer. The influence of SEMS placement on pathological alterations remains to be elucidated. AIM: To determine whether SEMS placement is associated with molecular or pathological features of colorectal carcinoma tissues. METHODS: Using a nonbiased molecular pathological epidemiology database of patients with obstructive colorectal cancers, we examined the association of SEMS placement with molecular or pathological features, including tumor size, histological type, American Joint Committee on Cancer (AJCC)-pTNM stage, and mutation statuses in colorectal cancer tissues compared with the use of transanal tubes. A multivariable logistic regression model was used to adjust for potential confounders. RESULTS: SEMS placement was significantly associated with venous invasion (P < 0.01), but not with the other features examined, including tumor size, disease stage, mutation status, and lymphatic invasion. In both the univariable and multivariable models with adjustment for potential factors including tumor location, histological type, and AJCC-pT stage, SEMS placement was significantly associated with severe venous invasion (P < 0.01). For the outcome category of severe venous invasion, the multivariable odds ratio for SEMS placement relative to transanal tube placement was 19.4 (95% confidence interval: 5.24-96.2). No significant differences of disease-free survival and overall survival were observed between SEMS and transanal tube groups. CONCLUSION: SEMS placement might be associated with severe venous invasion in colorectal cancer tissue, providing an impetus for further investigations on the pathological alterations by SEMSs in colorectal cancer development.

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To evaluate biological effects triggered by low levels of radiation, we established a uniquely sensitive experimental system to detect somatic mutations. By using the system, we found that mutant frequencies induced by X-rays were statistically significant at doses over 0.15 Gy, and a linear dose relationship with the mutant frequency was observed at doses over 0.15 Gy. The mutation spectra analysis revealed that mutation events generated by X-ray doses below 0.1 Gy were similar to those observed in unirradiated controls. In addition, a significant inflection point for both, the mutant frequency and the mutation spectra, was found at dose-rates around 11 mGy/day when cells were cultured in medium containing tritiated water. Because induced radiation-type events presented a clear dose/dose-rate dependency above the critical dose or the inflection point, these observations suggest that mutation events generated by radiation could change at a threshold dose-rate or a critical dose.

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Background: Sarcopenia is associated with poor prognosis in patients with colorectal cancer (CRC), but the mechanisms contributing to this association remain unclear. We hypothesized that skeletal muscle status is associated with tumor-infiltrating lymphocytes (TILs) in patients with CRC. Therefore, this study investigated the clinical effect of sarcopenia and its relationship with the local immune system in CRC patients. Methods: A total of 256 consecutive patients with CRC who underwent curative resection between 2008 and 2014 were enrolled. Sarcopenia was determined according to the skeletal muscle index (SMI), which was assessed using L3 skeletal muscle mass on axial computed tomography images, and its relationship with patient clinicopathological characteristics and survival was evaluated. Additionally, TILs (CD3+, CD8+, CD4+, and FOXP3+ T cells) were assayed by immunohistochemistry. The relationship between TILs and skeletal muscle status was evaluated. Results: Patients with a lower SMI showed significantly shorter recurrence-free and overall survival compared with those with a higher SMI. Low expression of TILs was associated with significantly shorter recurrence-free survival. SMI was significantly correlated with the number of CD3+ and CD8+ cells in the ordinal logistic regression analysis. Patients with low skeletal muscle status and low CD3+ and CD8+ cells had an unfavorable prognosis compared with patients with high skeletal muscle status and high CD3+ and CD8+ cells. Conclusion: Our data showed an association between skeletal muscle status and local immune cells, and this association may play a pivotal role in the clinical outcome of patients with CRC.

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The prognosis of oral cancer that has metastasized to the contralateral cervical lymph nodes is poor, although the appropriate treatment method has not been established because of its rarity. A multicenter retrospective study on the treatment and prognosis of pN2c oral cancer patients was conducted. We investigated the treatment and prognosis of 62 pN2c patients out of 388 pN+ patients with oral squamous cell carcinomas. Statistical analysis was performed on the various factors with overall survival (OS) and disease specific survival (DSS). In multivariate cox regression analysis, advanced T stage was significantly correlated with poor OS (p = 0.011) and DSS (p = 0.023) of patients with pN2c neck. In pN2c patients, OS, DSS, and neck control was not different between those undergoing ipsilateral neck dissection initially and those undergoing bilateral neck dissection. Thus, contralateral elective neck dissection is not recommended. The most important risk factor for prognosis in pN2c oral cancer patients is advanced T stage. No evidence was found to recommend contralateral elective neck dissection in clinically N1/2b patients. Therefore, the indication for contralateral elective neck dissection in N1/2b patients should be carefully determined in consideration of individual conditions.

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